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Sample records for single-dose randomized open-label

  1. Pharmacokinetics of a telmisartan/rosuvastatin fixed-dose combination: a single-dose, randomized, open-label, 2-period crossover study in healthy Korean subjects.

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    Chae, Dong Woo; Son, Mijeong; Kim, Yukyung; Son, Hankil; Jang, Seong Bok; Seo, Jeong Min; Nam, Su Youn; Park, Kyungsoo

    2015-10-01

    As hypertension and dyslipidemia are frequent comorbidities, antihypertensive drugs and lipid-lowering agents are often prescribed together for their treatment. Telmisartan and rosuvastatin are widely used together to treat hypertension and dyslipidemia. A combination formulation of these two drugs would improve patient compliance due to ease of dosing. The purpose of this study was to assess bioequivalence of single-dose administration of a newly-developed fixed-dose combination (FDC) tablet containing telmisartan/rosuvastatin 80/20 mg (test treatment) and coadministration of a telmisartan 80-mg tablet and a rosuvastatin 20-mg tablet (reference treatment) in healthy Korean male volunteers. This was a single-dose, randomized, open-label, 2-period crossover study enrolling healthy males aged 20 - 50 years with BMI between 18.5 and 25 kg/m2. Each subject received a single dose of the reference and test treatments with a 14-day washout period. Blood sampling was performed at prespecified intervals for up to 72 hours after dosing. Primary pharmacokinetic parameters were Cmax, AUClast, and AUC0-∞ of telmisartan, rosuvastatin, and N-desmethyl rosuvastatin. Bioequivalence was assessed by determining whether the 90% confidence intervals (CIs) of the geometric mean ratios (test treatment/reference treatment) of these parameters were within the standard range of 80% to 125%. Adverse events were monitored via regular interviews with the subjects and by physical examinations. 60 subjects were enrolled and 55 completed the study. The 90% CIs of the geometric mean ratios of Cmax, AUClast, and AUC00-∞ were 0.9262-1.1498, 0.9294-1.0313, and 0.9312-1.0320 for telmisartan, 0.9041-1.0428, 0.9262-1.0085, and 0.9307-1.0094 for rosuvastatin, and 0.8718-1.0022, 0.8901-0.9904, and 0.8872-0.9767 for N-desmethyl rosuvastatin, respectively. There was no statistical difference in the incidence of adverse events (AEs) (all of which were mild or moderate) between the reference and test

  2. A single dose, randomized, open-label, cross-over bioequivalence study of sildenafil citrate tablets in healthy Chinese volunteers
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    Li, Dai; Wang, Yu-Lu; Xu, Su-Mei; Li, Dan; Li, Xiao-Min; Pan, Jing; Xu, Ping-Sheng

    2017-02-01

    The present study was designed to evaluate the bioequivalence of a newly developed sildenafil citrate tablet 50 mg (Jinge®, Test) and a marketed counterpart (Viagra®, 100 mg, Reference) in healthy adult male Chinese volunteers. This single-dose, randomized, open-label, four-period, and two-treatment self-crossover study included two parts: fasting and postprandial studies. In each part of the study, the subjects were randomly assigned to receive test or reference products (100 mg sildenafil) in a 1 : 1 ratio, and then received the alternative products, following a 1-week washout period. Plasma sildenafil concentrations were analyzed by liquid chromatography-tandem mass spectrometry. Tolerability was assessed during the entire study period. 32 healthy volunteers (aged 19 - 30) were enrolled in the study; 31 volunteers completed the fasting study, while 32 volunteers completed the postprandial study. The test formulation was bioequivalent to the marketed formulation as the 90% CIs for the ratio of geometric means of Cmax (fasting: 98.79 - 119.61%; fed: 94.47 - 119.65%), AUClast (fasting: 98.70 - 109.71%; fed: 96.39 - 112.89%), and AUC∞ (fasting: 98.45 - 108.87%; fed: 96.36 - 112.74%) were within equivalence limits (80 - 125%) under both fasting and postprandial conditions. When sildenafil was given with high-fat meals, mean Cmax was reduced by 23%, and median tmax ranged from 0.75 to 1.50 hours (p ≤ 0.05). However, both AUClast and AUC∞ were comparable between fasting and postprandial conditions. No serious adverse events were found among the subjects. This study confirmed that test and reference sildenafil citrate tablets were bioequivalent under fasting and postprandial conditions.
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  3. Single-center open-label randomized study of anemia management improvement in ESRD patients with secondary hyperparathyroidism

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    Bellasi Antonio

    2016-04-01

    Full Text Available Whether anemia and mineral bone abnormalities (chronic kidney disease–mineral bone disorder [CKD-MBD] are associated still remains to be elucidated. Both anemia and CKD-MBD have been associated with adverse cardiovascular outcome and poor quality of life. However, recent evidence suggests that use of large doses of erythropoietin-stimulating agents (ESAs to correct hemoglobin (Hb may be detrimental in CKD. The Optimal Anemia Treatment in End Stage Renal Disease (ESRD (Optimal ESRD Treatment study will assess whether lowering of parathyroid hormone (PTH is associated with a reduction in ESA consumption. The Optimal ESRD Treatment study is a pilot single-center open-label study with blinded end point (a prospective randomized open blinded end-point [PROBE] design enrolling 50 patients on maintenance dialysis. Eligible patients with intact PTH (iPTH 300-540 pg/mL and Hb 10-11.5 g/dL will be randomized 1:1 to strict PTH control (150-300 pg/mL versus standard care (PTH range 300-540 pg/mL. Available drugs for CKD-MBD and anemia treatment will be managed by the attending physician to maintain the desired levels of PTH (according to study arm allocation and Hb (10-11.5 g/dL. Echocardiographic data for cardiac structure and function as well as arterial stiffness will be assessed at study inception and completion. The Optimal ESRD Treatment study should shed light on the complicated interplay of anemia and CKD-MBD and on the feasibility of clinical trials in this domain. The study results are expected in the spring of 2017.

  4. Randomized, open-label, single-dose, crossover, relative bioavailability study in healthy adults, comparing the pharmacokinetics of rabeprazole granules administered using soft food or infant formula as dosing vehicle versus suspension.

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    Thyssen, An; Solanki, Bhavna; Treem, William

    2012-07-01

    A sprinkle capsule formulation containing enteric-coated, delayed-release rabeprazole granules is being developed for the treatment of children with gastrointestinal reflux disease. The granules are designed to be mixed with vehicles that facilitate delivery to children, who may be unable to swallow solid formulations. The primary objective of this study-conducted on the sponsor's initiative-was to compare the bioavailability of rabeprazole granules when mixed with various dosing vehicles (small amount of soft food or infant formula) with that of a rabeprazole suspension with inactive vehicle granules (reference), to determine which dosing vehicle can be used to deliver rabeprazole in children. Tolerability was also assessed. This single-center, single-dose, randomized, open-label, 5-period crossover study was conducted in 35 healthy adult subjects. In a randomized sequence, fasting subjects received a single dose of 10-mg rabeprazole granules per treatment period, mixed with small amounts of 1 of 5 dosing vehicles (a strawberry-flavored suspension of rabeprazole granules with inactive vehicle granules reconstituted with water, yogurt [1 tablespoon], applesauce [1 tablespoon], or infant formula [5 mL], or a suspension of rabeprazole granules with inactive vehicle tablet reconstituted with water). Full plasma pharmacokinetic (PK) profiles of rabeprazole and its thioether metabolite were collected; concentrations were estimated via LC-MS/MS. PK properties were estimated using noncompartmental methods; 90% CIs around least squares mean test-to-reference ratios were calculated for C(max) and AUC values. All treatment-emergent adverse events (TEAEs) were recorded and assessed for severity (mild, moderate, or severe) and relationship to study drug. A total of 35 subjects were enrolled (mean age, 38 years; 54.3% female; 100% white; mean weight, 71.4 kg). Thirty-four subjects completed the study. Rabeprazole and rabeprazole thioether plasma PK properties were comparable

  5. Bioavailability of two single-dose oral formulations of omeprazole 20 mg: an open-label, randomized sequence, two-period crossover comparison in healthy Mexican adult volunteers.

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    Poo, Jorge Luis; Galán, Juan Francisco; Rosete, Alejandra; de Lago, Alberto; Oliva, Iván; González-de la Parra, Mario; Jiménez, Patricia; Burke-Fraga, Victoria; Namur, Salvador

    2008-04-01

    Omeprazole is a proton-pump inhibitor that acts to reduce acid secretion in the stomach and is used for treating various acid-related gastrointestinal disorders. There are several generic formulations of omeprazole available in Mexico; however, a literature search failed to identify published data concerning the bioavailability of these formulations in the Mexican population. The aim of this study was to compare the bioavailability of 2 oral formulations of omeprazole 20-mg capsules, marketed for use in Mexico, in healthy volunteers: Inhibitron (test formulation) and LosecA 20 mg (reference formulation). This study used a single-dose, open-label, randomized sequence, 2 x 2 crossover (2 administration periods x 2 treatments) design to compare the 2 formulations. Eligible subjects were healthy adult Mexican volunteers of both sexes. Subjects were randomly assigned in a 1:1 ratio to receive a single 20-mg dose of the test formulation followed by the reference formulation, or vice versa, with a 7-day washout period between administration periods. After a 12-hour (overnight) fast, subjects received a single, 20-mg dose of the corresponding formulation. Plasma samples were obtained over a 12-hour period after administration. Plasma omeprazole concentrations were analyzed by a nonstereospecific high-performance liquid chromatography method. For analysis of pharmacokinetic properties, including C(max), AUC from time 0 (baseline) to time t (AUC(0-t)), and AUC from baseline to infinity (AUC(0-infinity)), blood samples were drawn at baseline and 0.17, 0.33, 0.50, 0.75, 1, 1.25, 1.50, 1.75, 2, 2.50, 3, 4, 6, 8, and 12 hours after administration. The formulations were considered bioequivalent if the natural log (ln)-transformed ratios of C(max) and AUC were within the predetermined equivalence range of 80% to 125%, and if P disability, or required intervention to prevent permanent impairment or damage. Thirty-four subjects were enrolled and completed the study (25 men and 9

  6. Comparative bioavailability and tolerability of a single 20-mg dose of two fluoxetine hydrochloride dispersible tablet formulations in fasting, healthy Chinese male volunteers: an open-label, randomized-sequence, two-period crossover study.

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    Shi, Shaojun; Liu, Yani; Wu, Jianhong; Li, Zhongfang; Zhao, Yan; Zhong, Dafang; Zeng, Fandian

    2010-10-01

    The proprietary formulation of fluoxetine hydrochloride is an antidepressant of the selective serotonin reuptake inhibitor class. Pharmacokinetic studies investigating the bioequivalence of generic and branded formulations are needed to market generic fluoxetine in China. The aim of this study was to compare the bioavailability and tolerability of the proposed generic formulation with the established reference formulation of fluoxetine hydrochloride 20 mg in a fasting, healthy Chinese male population. This 10-week, open-label, randomized-sequence, single-dose, 2-period crossover study was conducted in healthy native Han Chinese male volunteers. Eligible subjects were randomly assigned in a 1:1 ratio to receive a single 20-mg dose of the test or reference formulation, followed by a 35-day washout period and administration of the alternate formulation. Doses were administered after a 12-hour overnight fast. For analysis of pharmacokinetic properties (including C(max), T(max), AUC(0-t), AUC(0-∞), and t(½)), blood samples were obtained over a 672-hour period after dosing. Plasma concentrations of fluoxetine and its active metabolite, norfluoxetine, were analyzed using a validated LC-MS/MS method. The formulations were to be considered bioequivalent if the ln-transformed ratios (test/ reference) of C(max) and AUC were within the predetermined bioequivalence range of 80% to 125%, as established by the US Food and Drug Administration, and if the P values were fasting, healthy Chinese male volunteers. Both formulations appeared to be well tolerated. Copyright © 2010 Excerpta Medica Inc. All rights reserved.

  7. Relative bioavailability of generic and branded 250-mg and 500-mg oral chlorphenesin carbamate tablets in healthy Korean volunteers: a single-dose, randomized-sequence, open-label, two-period crossover trial.

    Science.gov (United States)

    Yu, Ji-young; Song, Hyun Ho; Kim, Bo Gyeom; Park, Hyeon Ju; Choi, Kwang Sik; Kwon, Young Ee

    2009-11-01

    Chlorphenesin carbamate is a skeletal muscle relaxant approved in Korea for use in the treatment of pain and discomfort related to skeletal muscle trauma and inflammation. The aim of this study was to assess the bioequivalence of a generic formulation of chlorphenesin carbamate at doses of 250 and 500 mg and 2 branded formulations of the same doses in healthy Korean adults. This single-dose, randomized-sequence, open-label, 2-period crossover study was conducted in healthy Korean male and female volunteers. Subjects were assigned to receive, in a randomized sequence, a single dose of the generic (test) and branded (reference) formulations of chlorphenesin carbamate at a dose of 250 or 500 mg. Blood samples were drawn at 0, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 9, 12, and 15 hours after administration. Pharmacokinetic properties (C(max), T(max), AUC(0-t) AUC(0-infinity), t(1/2), and ke) were determined using HPLC. The formulations were to be considered bioequivalent if the 90% CIs of the treatment ratios of the geometric means of C(max) and AUC(0-t) were within a predetermined range of log 0.80 to log 1.25 based on regulatory criteria. Tolerability was assessed by monitoring for adverse events (AEs) on physical examination and/or e-mail and personal interview at the beginning and end of each study period. Twenty-eight subjects (22 men, 6 women) received chlorphenesin carbamate at the 250-mg dose, and 24 male subjects received the 500-mg dose. The mean (SD) ages of the subjects were 24.0 (2.6) and 24.0 (1.9) years in the 250- and 500-mg groups, respectively. No significant differences were found between the test and reference formulations (90% CIs: C(max), 1.0048-1.1153 with the 250-mg dose and 0.9630-1.1189 with the 500-mg dose; AUC(0-t), 0.9882-1.0546 and 0.9842-1.0578, respectively). No clinically significant AEs (upper gastric pain, abdominal bloating, pyrexia, edema, nausea, heartburn, constipation, headache, dizziness, drowsiness, or fatigue) were reported throughout

  8. Single Dose Versus 3 Doses of Intramuscular Benzathine Penicillin for Early Syphilis in HIV: A Randomized Clinical Trial.

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    Andrade, Roberto; Rodriguez-Barradas, Maria C; Yasukawa, Kosuke; Villarreal, Erick; Ross, Michael; Serpa, Jose A

    2017-03-15

    Patients coinfected with syphilis and human immunodeficiency virus (HIV) may have a slower decrease in rapid plasma reagin (RPR) titers. Currently a single dose of 2.4 million units of intramuscular benzathine penicillin G (BPG) is recommended for the treatment of early syphilis. Some observational studies have suggested that this regimen may lead to high failure rates in coinfected patients. We conducted an open-label randomized clinical trial to compare the efficacy of single-dose and 3-dose regimens of BPG for the treatment of early syphilis in HIV-infected individuals. RPR titers were monitored every 3 months. Treatment success was defined as a decrease in RPR titers of ≥2 dilutions (4-fold) during a 12-month follow-up period. Sixty-four patients were included. In the intention-to-treat analysis, treatment success rates were 80% (28 of 35 subjects) and 93% (27 of 29 subjects) in the single-dose and 3-dose regimens, respectively (absolute difference, 13% [95% confidence interval {CI}, -5% to 30%; P = .17). In the per-protocol analysis, success rates were 93% (27 of 29) and 100% in the single-dose and 3-dose regimens, respectively (absolute difference, 7% [95% CI, -7% to 22%]; P = .49). CD4 T-cell count, RPR titer and syphilis stage did not affect treatment results. When compared with a single dose of BPG, a 3-dose regimen did not improve syphilis serological outcomes. Our results support the Centers for Disease Control and Prevention recommendation of a single dose of BPG in HIV-infected patients with early syphilis. NCT02611765. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  9. Pharmacokinetic comparison of controlled-release and immediate-release oral formulations of simvastatin in healthy Korean subjects: a randomized, open-label, parallel-group, single- and multiple-dose study.

    Science.gov (United States)

    Jang, Seong Bok; Lee, Yoon Jung; Lim, Lay Ahyoung; Park, Kyung-Mi; Kwon, Bong-Ju; Woo, Jong Soo; Kim, Yong-Il; Park, Min Soo; Kim, Kyung Hwan; Park, Kyungsoo

    2010-01-01

    A controlled-release (CR) formulation of simvastatin was recently developed in Korea. The formulation is expected to yield a lower C(max) and similar AUC values compared with the immediate-release (IR) formulation. The goal of this study was to compare the pharmacokinetics of the new CR formulation and an IR formulation of simvastatin after single- and multiple-dose administration in healthy Korean subjects. This study was developed as part of a product development project at the request of the Korean regulatory agency. This was a randomized, open-label, parallelgroup, 2-part study. Eligible subjects were healthy male or female volunteers between the ages of 19 and 55 years and within 20% of their ideal weight. In part I, each subject received a single dose of the CR or IR formulation of simvastatin 40 mg orally (20 mg x 2 tablets) after fasting. In part II, each subject received the same dose of the CR or IR formulation for 8 consecutive days. Blood samples were obtained for 48 hours after the dose in part I and after the first and the last dose in part II. Pharmacokinetic parameters were determined for both simvastatin (the inactive prodrug) and simvastatin acid (the active moiety). An adverse event (AE) was defined as any unfavorable sign (including an abnormal laboratory finding) or symptom, regardless of whether it had a causal relationship with the study medication. Serious AEs were defined as any events that are considered life threatening, require hospitalization or prolongation of existing hospitalization, cause persistent or significant disability or incapacity, or result in congenital abnormality, birth defect, or death. AEs were determined based on patient interviews and physical examinations. Twenty-four healthy subjects (17 men, 7 women; mean [SD] age, 29 [7] years; age range, 22-50 years) were enrolled in part I, and 29 subjects (17 men, 12 women; mean age, 33 [9] years; age range, 19-55 years) were enrolled in part II. For simvastatin acid, C

  10. Average bioequivalence of single 500 mg doses of two oral formulations of levofloxacin: a randomized, open-label, two-period crossover study in healthy adult Brazilian volunteers

    Directory of Open Access Journals (Sweden)

    Eunice Kazue Kano

    2015-03-01

    Full Text Available Average bioequivalence of two 500 mg levofloxacin formulations available in Brazil, Tavanic(c (Sanofi-Aventis Farmacêutica Ltda, Brazil, reference product and Levaquin(c (Janssen-Cilag Farmacêutica Ltda, Brazil, test product was evaluated by means of a randomized, open-label, 2-way crossover study performed in 26 healthy Brazilian volunteers under fasting conditions. A single dose of 500 mg levofloxacin tablets was orally administered, and blood samples were collected over a period of 48 hours. Levofloxacin plasmatic concentrations were determined using a validated HPLC method. Pharmacokinetic parameters Cmax, Tmax, Kel, T1/2el, AUC0-t and AUC0-inf were calculated using noncompartmental analysis. Bioequivalence was determined by calculating 90% confidence intervals (90% CI for the ratio of Cmax, AUC0-t and AUC0-inf values for test and reference products, using logarithmic transformed data. Tolerability was assessed by monitoring vital signs and laboratory analysis results, by subject interviews and by spontaneous report of adverse events. 90% CIs for Cmax, AUC0-t and AUC0-inf were 92.1% - 108.2%, 90.7% - 98.0%, and 94.8% - 100.0%, respectively. Observed adverse events were nausea and headache. It was concluded that Tavanic(c and Levaquin(c are bioequivalent, since 90% CIs are within the 80% - 125% interval proposed by regulatory agencies.

  11. Open-Label Single-Sequence Crossover Study Evaluating Pharmacokinetics, Efficacy, and Safety of Once-Daily Dosing of Nitisinone in Patients with Hereditary Tyrosinemia Type 1.

    Science.gov (United States)

    Guffon, Nathalie; Bröijersén, Anders; Palmgren, Ingrid; Rudebeck, Mattias; Olsson, Birgitta

    2018-01-01

    Although nitisinone is successfully used to treat hereditary tyrosinemia type 1 (HT-1) with the recommended twice-daily dosing, data describing a long half-life motivate less frequent dosing. Therefore, in agreement with the Pharmacovigilance Risk Assessment Committee at the European Medicines Agency, this study was performed to investigate the switch to once-daily dosing. This open-label, non-randomized, single-sequence crossover study evaluated the pharmacokinetics, efficacy, and safety of once-daily compared to twice-daily dosing of nitisinone in patients with HT-1 (NCT02323529). Well-controlled patients of dry blood spots by tandem mass spectrometry. The primary endpoint was C min of nitisinone after ≥4 weeks of treatment on each dosing regimen. Secondary objectives were evaluation of efficacy and safety during each dosing regimen. In total, 19 patients were enrolled and 17 included in the per-protocol analysis set. The mean (SD) nitisinone C min decreased by 23%, from 26.4 (10.2) to 21.2 (9.9) μmol/L in dry blood spot samples (not equivalent to plasma concentrations), when patients switched from twice- to once-daily dosing. There was no apparent age- or bodyweight-related trend in the degree of C min decrease. No patient had quantifiable succinylacetone levels during the once-daily treatment period, indicating efficacious treatment. All adverse events were mild or moderate and judged unrelated to nitisinone. The switch to once-daily treatment with nitisinone appeared efficacious and safe in the treatment of patients with HT-1.

  12. Relative bioequivalence evaluation of two oral atomoxetine hydrochloride capsules: a single dose, randomized, open-label, 2-period crossover study in healthy Chinese volunteers under fasting conditions.

    Science.gov (United States)

    Shang, D-W; Guo, W; Zhou, F-C; Wang, X-P; Li, A-N; Zhang, L; Li, W-B; Lu, W; Wang, C-Y

    2013-11-01

    To evaluate the bioequivalence of a new formulation of atomoxetine hydrochloride (CAS 82248-59-7) capsules (test) and an available branded capsules (reference) after administration of a single 40 mg dose, randomized, open-label, 2-period crossover study was conducted in 22 healthy male Chinese subjects with a 1-week wash-out period. This study was designed for/the Honglin Pharmaceutical Co. Ltd and contracted to be done by the Beijing Anding Hospital in order to satisfy Chinese regulatory requirements to allow marketing of this generic product and performed according to the criteria of SFDA. Blood samples were collected before and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16 and 24 h after drug administration. Plasma concentrations were determined by high-performance liquid chromatography (HPLC) with UV detection. A non-compartmental method was used to calculate the pharmacokinetic parameters and evaluate bioequivalence of the 2 formulations. The 90% confidence interval (CI) of the ratios (test/reference) of atomoxetine for AUC0-24, AUC0-∞ and Cmax were 100.9% (93.6-108.8%), 103.1% (95.1-111.7%) and 105.2% (92.8-119.4%), respectively, which fell within the interval of 80-125% and 75-133%. No clinically significant changes or abnormalities were noted in laboratory data and vital signs. From these results it can be concluded that the test formulation of atomoxetine capsules met the regulatory criterion for bioequivalence to the reference formulation. © Georg Thieme Verlag KG Stuttgart · New York.

  13. Relative bioavailability of generic and branded acetylcysteine effervescent tablets: A single-dose, open-label, randomized-sequence, two-period crossover study in fasting healthy Chinese male volunteers.

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    Liu, Yan-Mei; Liu, Yun; Lu, Chuan; Jia, Jing-Ying; Liu, Gang-Yi; Weng, Li-Ping; Wang, Jia-Yan; Li, Guo-Xiu; Wang, Wei; Li, Shui-Jun; Yu, Chen

    2010-11-01

    Acetylcysteine may be used as a muco- lytic agent for the treatment of chronic bronchitis, chronic obstructive pulmonary disease, and other pulmonary diseases complicated by the production of viscous mucus. However, little is known of its pharmacokinetic properties when given orally in healthy volunteers, particularly in a Chinese Han population. This study was conducted to provide support for the marketing of a generic product in China. The purpose of this study was to compare the pharmacokinetics and relative bioavailability of a generic test formulation and a branded reference formulation of acetylcysteine in fasting healthy Chinese male volunteers. A single-dose, open-label, randomized-sequence, 2-period crossover design with a 7-day washout period between doses was used in this study. Healthy Chinese male nonsmokers aged 18 to 40 years with a body mass index (BMI) of 19 to 25 kg/m(2) were selected. Eligible volunteers were randomly assigned to receive acetylcysteine 600 mg PO as either the test formulation (3 tablets of 200 mg each) or reference formulation (1 tablet of 600 mg) under fasting conditions. A total of 15 serial blood samples were collected over a 24-hour interval, and total plasma acetylcysteine concentrations were analyzed by a validated liquid chromatography-isotopic dilution mass spectrometry method. Pharmacokinetic parameters (C(max), T(max), t(½) AUC(0-t), and AUC(0-∞) were calculated and analyzed statistically. The 2 formulations were considered bioequivalent if the 90% CIs of the log-transformed ratios (test/reference) of C(max) and AUC were within the predetermined bioequivalence ranges (70%-143% for C(max); 80%-125% for AUC), as established by the State Food and Drug Administration of China. Tolerability was determined by vital signs, clinical laboratory tests, 12-lead ECGs, physical examinations, and interviews with the subjects about adverse events (AEs). A total of 24 healthy Chinese Han male volunteers were enrolled in and

  14. Relative bioavailability of two oral formulations of risperidone 2 mg: A single-dose, randomized-sequence, open-label, two-period crossover comparison in healthy Brazilian volunteers.

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    Belotto, Karisa Cristina Rodrigues; Raposo, Nádia Rezende Barbosa; Ferreira, Aline Siqueira; Gattaz, Wagner Farid

    2010-11-01

    Risperidone (RSP) is a benzisoxazole antipsychotic agent used to treat schizophrenia and other psychiatric illnesses in adults and children (including those with autism). After oral administration, RSP is completely absorbed from the gastrointestinal tract and undergoes hydroxylation to yield 9-hydroxyrisperidone (9-OH-RSP), an active metabolite that has a pharmacologic profile and potency similar to RSP. The aims of this study were to compare the relative bioavailability of a pharmaceutical-equivalent (test) formulation with a reference formulation of oral RSP 2 mg, both available commercially on the Brazilian pharmaceutical market, and to generate data regarding the oral bioavailability of the tested drug in healthy Brazilian volunteers. This single-dose, randomized-sequence, open-label, 2-period crossover study was conducted in healthy Brazilian volunteers from August to December 2008. Subjects were randomly assigned to receive the test formulation followed by the reference formulation or vice versa, with a 30-day washout period between doses. Study drugs were administered after a 12-hour overnight fast. For pharmacokinetic analysis, blood samples were drawn at 0 (baseline), 0.25, 0.5, 1, 1.5, 3, 5, 8, 12, 24, 48, 72, 96, and 120 hours after administration. Plasma concentrations of RSP and 9-OH-RSP were determined using LC-MS/MS. The test and reference formulations were to be considered bioequivalent if the 90% CIs for the geometric mean test/reference ratios were within a predetermined range of 80% to 125%, in accordance with the policies of the Brazilian Sanitary Surveillance Agency and the US Food and Drug Administration. Tolerability was determined using clinical assessments, monitoring of vital signs, analysis of laboratory test results, and subject interviews regarding adverse events. A total of 22 subjects were enrolled (11 men, 11 women; mean [SD] age, 32 [12] years [range, 1858 years]; weight, 70.4 [11.9] kg [range, 50-103 kg]; height, 1.67 [0.08] m

  15. Pharmacokinetic comparison of sustained- and immediate-release oral formulations of cilostazol in healthy Korean subjects: a randomized, open-label, 3-part, sequential, 2-period, crossover, single-dose, food-effect, and multiple-dose study.

    Science.gov (United States)

    Lee, Donghwan; Lim, Lay Ahyoung; Jang, Seong Bok; Lee, Yoon Jung; Chung, Jae Yong; Choi, Jong Rak; Kim, Kiyoon; Park, Jin Woo; Yoon, Hosang; Lee, Jaeyong; Park, Min Soo; Park, Kyungsoo

    2011-12-01

    A sustained-release (SR) formulation of cilostazol was recently developed in Korea and was expected to yield a lower C(max) and a similar AUC to the immediate-release (IR) formulation. The goal of the present study was to compare the pharmacokinetic profiles of a newly developed SR formulation and an IR formulation of cilostazol after single- and multiple-dose administration and to evaluate the influence of food in healthy Korean subjects. This study was developed as part of a product development project at the request of the Korean regulatory agency. This was a randomized, 3-part, sequential, open-label, 2-period crossover study. Each part consisted of different subjects between the ages of 19 and 55 years. In part 1, each subject received a single dose of SR (200 mg × 1 tablet, once daily) and IR (100 mg × 2 tablets, BID) formulations of cilostazol orally 7 days apart in a fasted state. In part 2, each subject received a single dose of the SR (200 mg × 1 tablet, once daily) formulation of cilostazol 7 days apart in a fasted and a fed state. In part 3, each subject received multiple doses of the 2 formulations for 8 consecutive days 21 days apart. Blood samples were taken for 72 hours after the dose. Cilostazol pharmacokinetics were determined for both the parent drug and its metabolites (OPC-13015 and OPC-13213). Adverse events were evaluated through interviews and physical examinations. Among the 92 enrolled subjects (66 men, 26 women; part 1, n = 26; part 2, n = 26; part 3, n = 40), 87 completed the study. In part 1, all the primary pharmacokinetic parameters satisfied the criterion for assumed bioequivalence both in cilostazol and its metabolites, yielding 90% CI ratios of 0.9624 to 1.2323, 0.8873 to 1.1208, and 0.8919 to 1.1283 for C(max) and 0.8370 to 1.0134, 0.8204 to 0.9807, and 0.8134 to 0.9699 for AUC(0-last) of cilostazol, OPC-13015, and OPC-13213, respectively. In part 2, food intake increased C(max) and AUC significantly (P food and 23 with a high

  16. Comparative fasting bioavailability of 2 bepotastine formulations in healthy male Chinese volunteers: an open-label, randomized, single-dose, 2-way crossover study.

    Science.gov (United States)

    Shentu, Jianzhong; Zhou, Huili; Hu, Xingjiang; Wu, Guolan; Wu, Lihua; Zhu, Meixiang; Zhai, You; Zheng, Yunliang; Liu, Jian

    2014-04-01

    Bepotastine is a second-generation histamine1 receptor antagonist that is used in the treatment of allergic rhinitis, urticaria, and pruritus associated with skin disease. A new generic formulation of bepotastine has been developed in China, and information concerning bioavailability and pharmacokinetic properties in the Chinese population has not been reported. The aim of the present study was to compare the bioavailability and pharmacokinetic properties of 2 tablet formulations of bepotastine, the 10-mg generic formulation (test) and a branded formulation (reference), in healthy male Chinese volunteers to obtain registration approval of the test formulation. A single-center, open-label, randomized, 2-way crossover study with a 1-week washout period was conducted in 24 healthy male volunteers. Blood samples were collected for 16 hours after a single dose of the 10-mg bepotastine test formulation or the reference formulation. Plasma bepotastine concentrations were determined using a validated LC-MS/MS method. Cmax, Tmax, AUC₀-t, AUC₀-∞, and t½ were determined using noncompartmental analysis. The formulations were considered bioequivalent if the 90% CIs for the log-transformed Cmax and AUC values were within the predetermined interval of 75% to 133% and 80% to 125%, respectively, according to the guidelines of the China Food and Drug Administration. No significant differences were found in mean (SD) pharmacokinetic parameters between the test and reference drugs, including Cmax (74.81 [9.91] ng/mL vs 78.60 [29.58] ng/mL), AUC₀-t (295.55[115.29] ng·h/mL vs 299.17[109.29] ng·h/mL), and AUC0-∞ (305.28 [118.50] ng·h/mL vs 310.90 [112.20] ng·h/mL). The mean (SD) t½ values of the test and reference formulations were 2.53 (0.50) hours and 2.62 (0.41) hours, respectively. The 90% CIs of the treatment ratios for the logarithmic transformed values of Cmax, AUC₀-t, and AUC₀-∞ were 86.96% to 101.80%, 93.22% to 104.13%, and 92.66% to 103.30%, respectively

  17. An Open-label, Single-dose, Pharmacokinetic Study of Factor VIII Activity After Administration of Moroctocog Alfa (AF-CC) in Male Chinese Patients With Hemophilia A.

    Science.gov (United States)

    Liu, Hongzhong; Wu, Runhui; Hu, Pei; Sun, Feifei; Xu, Lihong; Liang, Yali; Nepal, Sunil; Qu, Peng Roger; Huard, Francois; Korth-Bradley, Joan M

    2017-07-01

    Hemophilia A represents up to 80% of all hemophilia cases in China. In patients with this condition, bleeding can be prevented and controlled by administering clotting factor VIII (FVIII). Since their initial availability, recombinant FVIII products have undergone several iterations to enhance their safety. Moroctocog alfa albumin-free cell culture (AF-CC) is among the third generation of recombinant FVIII products and received regulatory approval in China in August 2012. The present study characterizes the single-dose pharmacokinetic parameters of FVIII activity (FVIII:C) after administration of moroctocog alfa (AF-CC) in male Chinese patients with hemophilia A. This multicenter, open-label, single-dose study enrolled 13 male Chinese patients diagnosed with severe hemophilia A (FVIII:C hemophilia A. The pharmacokinetic profile in older patients was similar to that previously reported with recombinant FVIII products in studies with a predominantly white population; younger patients had reduced exposure to FVIII:C. The single doses of moroctocog alfa (AF-CC) were well tolerated; 2 cases of transient, low-titer FVIII inhibitor development were observed. ClinicalTrials.gov identifier: NCT02461992. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

  18. Randomized open-label trial of dextromethorphan in Rett syndrome.

    Science.gov (United States)

    Smith-Hicks, Constance L; Gupta, Siddharth; Ewen, Joshua B; Hong, Manisha; Kratz, Lisa; Kelley, Richard; Tierney, Elaine; Vaurio, Rebecca; Bibat, Genila; Sanyal, Abanti; Yenokyan, Gayane; Brereton, Nga; Johnston, Michael V; Naidu, Sakkubai

    2017-10-17

    To determine safety and perform a preliminary assessment of dose-dependent efficacy of dextromethorphan in normalizing electrographic spikes, clinical seizures, and behavioral and cognitive functions in girls with Rett syndrome. We used a prospective randomized, open-label trial in fast metabolizers of dextromethorphan to examine the effect of dextromethorphan on core clinical features of Rett syndrome. Interictal spike activity and clinical seizures were determined using EEG and parent reporting. Cognitive data were obtained using the Mullen Scales of Early Learning and Vineland Adaptive Behavior Scales, while behavioral data were obtained from parent-completed checklists, the Aberrant Behavior Checklist-Community Version, and the Screen for Social Interaction. Anthropometric data were obtained according to the National Health and Nutrition Examination Survey. The Rett Syndrome Severity Scale provided a clinical global impression of the effect of dextromethorphan on clinical severity. Dextromethorphan is safe for use in 3- to 15-year-old girls with Rett syndrome. Thirty-five girls were treated with 1 of 3 doses of dextromethorphan over a period of 6 months. Statistically significant dose-dependent improvements were seen in clinical seizures, receptive language, and behavioral hyperactivity. There was no significant improvement in global clinical severity as measured by the Rett Syndrome Severity Scale. Dextromethorphan is a potent noncompetitive antagonist of the NMDA receptor channel that is safe for use in young girls with Rett syndrome. Preliminary evidence suggests that dextromethorphan may improve some core features of Rett syndrome. This study provides Class IV evidence that dextromethorphan at various doses does not change EEG spike counts over 6 months, though precision was limited to exclude an important effect. © 2017 American Academy of Neurology.

  19. Influence of Renal Impairment on the Pharmacokinetics of Afatinib: An Open-Label, Single-Dose Study.

    Science.gov (United States)

    Wiebe, Sabrina; Schnell, David; Külzer, Raimund; Gansser, Dietmar; Weber, Anne; Wallenstein, Gudrun; Halabi, Atef; Conrad, Anja; Wind, Sven

    2017-06-01

    Afatinib is an oral irreversible ErbB-Family Blocker indicated for treatment of patients with EGFR mutation positive advanced non-small cell lung cancer. This trial assessed whether renal impairment influences the pharmacokinetics and safety of afatinib. This was an open-label, single-dose study. Pharmacokinetic parameters after afatinib 40 mg were investigated in subjects with moderate (n = 8) or severe (n = 8) renal impairment (estimated glomerular filtration rate 30-59 mL/min/1.73 m 2 and 15-29 mL/min/1.73 m 2 , respectively) and healthy matched controls (n = 14). Plasma and urine samples were collected before and up to 14 days after dosing for pharmacokinetic and plasma protein-binding assessment. Primary endpoints were area under the plasma concentration-time curve from time zero to the last quantifiable concentration (AUC last ) and maximum plasma concentration (C max ) between subjects with renal impairment and healthy matched controls. Pharmacokinetic profiles and plasma protein binding were similar in all groups. The extent of exposure, as indicated by AUC last and C max , was generally similar between the matched treatment groups, with the exception of the geometric mean ratio of AUC last for subjects with severe renal impairment, which showed a trend towards a higher value compared with matched healthy subjects (150.0 % [90 % CI 105.3-213.7]) Inter-individual variability was moderate (geometric mean coefficient of variation 28-39 % for moderate impairment, 34-42 % for severe impairment). Afatinib was well tolerated and urinary excretion was minimal. Moderate-to-severe renal impairment had a minor influence on the pharmacokinetics of afatinib that was within the observed inter-individual variability, suggesting that afatinib treatment can be considered in this patient population. Registered at ClinicalTrials.gov as NCT02096718.

  20. An accelerated dose escalation with a grass pollen allergoid is safe and well-tolerated: a randomized open label phase II trial.

    Science.gov (United States)

    Chaker, A M; Al-Kadah, B; Luther, U; Neumann, U; Wagenmann, M

    2015-01-01

    The number of injections in the dose escalation of subcutaneous immunotherapy (SCIT) is small for some currently used hypoallergenic allergoids, but can still be inconvenient to patients and can impair compliance. The aim of this trial was to compare safety and tolerability of an accelerated to the conventional dose escalation scheme of a grass pollen allergoid. In an open label phase II trial, 122 patients were 1:1 randomized for SCIT using a grass pollen allergoid with an accelerated dose escalation comprising only 4 weekly injections (Group I) or a conventional dose escalation including 7 weekly injections (Group II). Safety determination included the occurrence of local and systemic adverse events. Tolerability was assessed by patients and physicians. Treatment-related adverse events were observed in 22 (36.1 %) patients in Group I and 15 (24.6 %) in Group II. Local reactions were reported by 18 patients in Group I and 11 in Group II. Five Grade 1 systemic reactions (WAO classification) were observed in Group I and 2 in Group II. Grade 2 reactions occurred 3 times in Group I and 2 times in Group II. Tolerability was rated as "good" or "very good" by 53 (86.9 %) patients in Group I and 59 (100 %) in Group II by investigators. Forty-eight patients in Group I (80.0 %) and 54 in Group II (91.5 %) rated tolerability as "good" or "very good". The dose escalation of a grass pollen allergoid can be accelerated with safety and tolerability profiles comparable to the conventional dose escalation.

  1. Pharmacokinetics of serelaxin in patients with hepatic impairment: a single-dose, open-label, parallel group study.

    Science.gov (United States)

    Kobalava, Zhanna; Villevalde, Svetlana; Kotovskaya, Yulia; Hinrichsen, Holger; Petersen-Sylla, Marc; Zaehringer, Andreas; Pang, Yinuo; Rajman, Iris; Canadi, Jasna; Dahlke, Marion; Lloyd, Peter; Halabi, Atef

    2015-06-01

    Serelaxin is a recombinant form of human relaxin-2 in development for treatment of acute heart failure. This study aimed to evaluate the pharmacokinetics (PK) of serelaxin in patients with hepatic impairment. Secondary objectives included evaluation of immunogenicity, safety and tolerability of serelaxin. This was an open-label, parallel group study (NCT01433458) comparing the PK of serelaxin following a single 24 h intravenous (i.v.) infusion (30 μg kg(-1)  day(-1) ) between patients with mild, moderate or severe hepatic impairment (Child-Pugh class A, B, C) and healthy matched controls. Blood sampling and standard safety assessments were conducted. Primary non-compartmental PK parameters [including area under the serum concentration-time curve AUC(0-48 h) and AUC(0-∞) and serum concentration at 24 h post-dose (C24h )] were compared between each hepatic impairment group and healthy controls. A total of 49 subjects (including 25 patients with hepatic impairment) were enrolled, of which 48 subjects completed the study. In all groups, the serum concentration of serelaxin increased over the first few hours of infusion, reached steady-state at 12-24 h and then declined following completion of infusion, with a mean terminal half-life of 7-8 h. All PK parameter estimates were comparable between each group of patients with hepatic impairment and healthy controls. No serious adverse events, discontinuations due to adverse events or deaths were reported. No serelaxin treatment-related antibodies developed during this study. The PK and safety profile of serelaxin were not affected by hepatic impairment. No dose adjustment is needed for serelaxin treatment of 48 h i.v. infusion in patients with hepatic impairment. © 2014 The British Pharmacological Society.

  2. Comparison of the pharmacokinetics of a new 30 mg modified-release tablet formulation of metoclopramide for once-a-day administration versus 10 mg immediate-release tablets: a single and multiple-dose, randomized, open-label, parallel study in healthy male subjects.

    Science.gov (United States)

    Bernardo-Escudero, Roberto; Alonso-Campero, Rosalba; Francisco-Doce, María Teresa de Jesús; Cortés-Fuentes, Myriam; Villa-Vargas, Miriam; Angeles-Uribe, Juan

    2012-12-01

    The study aimed to assess the pharmacokinetics of a new, modified-release metoclopramide tablet, and compare it to an immediate-release tablet. A single and multiple-dose, randomized, open-label, parallel, pharmacokinetic study was conducted. Investigational products were administered to 26 healthy Hispanic Mexican male volunteers for two consecutive days: either one 30 mg modified-release tablet every 24 h, or one 10 mg immediate-release tablet every 8 h. Blood samples were collected after the first and last doses of metoclopramide. Plasma metoclopramide concentrations were determined by high-performance liquid chromatography. Safety and tolerability were assessed through vital signs measurements, clinical evaluations, and spontaneous reports from study subjects. All 26 subjects were included in the analyses [mean (SD) age: 27 (8) years, range 18-50; BMI: 23.65 (2.22) kg/m², range 18.01-27.47)]. Peak plasmatic concentrations were not statistically different with both formulations, but occurred significantly later (p 0.05)]. One adverse event was reported in the test group (diarrhea), and one in the reference group (headache). This study suggests that the 30 mg modified-release metoclopramide tablets show features compatible with slow-release formulations when compared to immediate-release tablets, and is suitable for once-a-day administration.

  3. Once-daily dose regimen of ribavirin is interchangeable with a twice-daily dose regimen: randomized open clinical trial

    Directory of Open Access Journals (Sweden)

    Balk JM

    2015-08-01

    Full Text Available Jiska M Balk,1 Guido RMM Haenen,1 Özgür M Koc,2 Ron Peters,3 Aalt Bast,1 Wim JF van der Vijgh,1 Ger H Koek,4 1Department of Toxicology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, 2Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, 3DSM Resolve, Geleen, 4Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre, Maastricht, the Netherlands Background: The combination of ribavirin (RBV and pegylated interferon (PEG-IFN is effective in the treatment of chronic hepatitis C infection. Reducing the frequency of RBV intake from twice to once a day will improve compliance and opens up the opportunity to combine RBV with new and more specific direct-acting agents in one pill. Therefore, the purpose of this study was to evaluate the pharmacokinetic profile of RBV in a once-daily to twice-daily regimen. The secondary aim was to determine tolerability as well as the severity and differences in side effects of both treatment regimens. Methods: In this randomized open-label crossover study, twelve patients with chronic type 1 hepatitis C infection and weighing more than 75 kg were treated with 180 µg of PEG-IFN weekly and 1,200 mg RBV daily for 24 weeks. The patients received RBV dosed as 1,200 mg once-daily for 12 weeks followed by RBV dosed as 600 mg twice-daily for 12 weeks, or vice versa. In addition to the pharmacokinetic profile, the hematological profile and side effects were recorded. The RBV concentrations in plasma were determined using liquid chromatography-tandem mass spectrometry. Results: Eight of twelve patients completed the study. Neither the time taken for RBV to reach peak plasma concentration nor the AUC0-last (adjusted for difference in dose was significantly different between the two groups (P>0.05. Furthermore, the once-daily regimen did not give more side effects than the twice-daily regimen (P>0

  4. Bioavailability of everolimus administered as a single 5 mg tablet versus five 1 mg tablets: a randomized, open-label, two-way crossover study of healthy volunteers.

    Science.gov (United States)

    Thudium, Karen; Gallo, Jorge; Bouillaud, Emmanuel; Sachs, Carolin; Eddy, Simantini; Cheung, Wing

    2015-01-01

    The mammalian target of rapamycin (mTOR) inhibitor everolimus has a well-established pharmacokinetics profile. We conducted a randomized, single-center, open-label, two-sequence, two-period crossover study of healthy volunteers to assess the relative bioavailability of everolimus administered as one 5 mg tablet or five 1 mg tablets. Subjects were randomized 1:1 to receive everolimus dosed as one 5 mg tablet or as five 1 mg tablets on day 1, followed by a washout period on days 8-14 and then the opposite formulation on day 15. Blood sampling for pharmacokinetic evaluation was performed at prespecified time points, with 17 samples taken for each treatment period. Primary variables for evaluation of relative bioavailability were area under the concentration-time curve from time zero to infinity (AUCinf) and maximum blood concentration (Cmax). Safety was assessed by reporting the incidence of adverse events (AEs). Twenty-two participants received everolimus as one 5 mg tablet followed by five 1 mg tablets (n=11) or the opposite sequence (n=11). The Cmax of five 1 mg tablets was 48% higher than that of one 5 mg tablet (geometric mean ratio, 1.48; 90% confidence interval [CI], 1.35-1.62). AUCinf was similar (geometric mean ratio, 1.08; 90% CI, 1.02-1.16), as were the extent of absorption and the distribution and elimination kinetics. AEs, all grade 1 or 2, were observed in 54.5% of subjects. Although the extent of absorption was similar, the Cmax of five 1 mg tablets was higher than that of one 5 mg tablet, suggesting these formulations lead to different peak blood concentrations and are not interchangeable at the dose tested.

  5. Bioavailability of Lumefantrine Is Significantly Enhanced with a Novel Formulation Approach, an Outcome from a Randomized, Open-Label Pharmacokinetic Study in Healthy Volunteers.

    Science.gov (United States)

    Jain, Jay Prakash; Leong, F Joel; Chen, Lan; Kalluri, Sampath; Koradia, Vishal; Stein, Daniel S; Wolf, Marie-Christine; Sunkara, Gangadhar; Kota, Jagannath

    2017-09-01

    The artemether-lumefantrine combination requires food intake for the optimal absorption of lumefantrine. In an attempt to enhance the bioavailability of lumefantrine, new solid dispersion formulations (SDF) were developed, and the pharmacokinetics of two SDF variants were assessed in a randomized, open-label, sequential two-part study in healthy volunteers. In part 1, the relative bioavailability of the two SDF variants was compared with that of the conventional formulation after administration of a single dose of 480 mg under fasted conditions in three parallel cohorts. In part 2, the pharmacokinetics of lumefantrine from both SDF variants were evaluated after a single dose of 480 mg under fed conditions and a single dose of 960 mg under fasted conditions. The bioavailability of lumefantrine from SDF variant 1 and variant 2 increased up to ∼48-fold and ∼24-fold, respectively, relative to that of the conventional formulation. Both variants demonstrated a positive food effect and a less than proportional increase in exposure between the 480-mg and 960-mg doses. Most adverse events (AEs) were mild to moderate in severity and not suspected to be related to the study drug. All five drug-related AEs occurred in subjects taking SDF variant 2. No clinically significant treatment-emergent changes in vital signs, electrocardiograms, or laboratory blood assessments were noted. The solid dispersion formulation enhances the lumefantrine bioavailability to a significant extent, and SDF variant 1 is superior to SDF variant 2. Copyright © 2017 Jain et al.

  6. Efficacy, safety and tolerability of ongoing statin plus ezetimibe versus doubling the ongoing statin dose in hypercholesterolemic Taiwanese patients: an open-label, randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Yu Chih-Chieh

    2012-05-01

    Full Text Available Abstract Background Reducing low-density lipoprotein cholesterol (LDL-C is associated with reduced risk for major coronary events. Despite statin efficacy, a considerable proportion of statin-treated hypercholesterolemic patients fail to reach therapeutic LDL-C targets as defined by guidelines. This study compared the efficacy of ezetimibe added to ongoing statins with doubling the dose of ongoing statin in a population of Taiwanese patients with hypercholesterolemia. Methods This was a randomized, open-label, parallel-group comparison study of ezetimibe 10 mg added to ongoing statin compared with doubling the dose of ongoing statin. Adult Taiwanese hypercholesterolemic patients not at optimal LDL-C levels with previous statin treatment were randomized (N = 83 to ongoing statin + ezetimibe (simvastatin, atorvastatin or pravastatin + ezetimibe at doses of 20/10, 10/10 or 20/10 mg or doubling the dose of ongoing statin (simvastatin 40 mg, atorvastatin 20 mg or pravastatin 40 mg for 8 weeks. Percent change in total cholesterol, LDL-C, high-density lipoprotein cholesterol (HDL-C and triglycerides, and specified safety parameters were assessed at 4 and 8 weeks. Results At 8 weeks, patients treated with statin + ezetimibe experienced significantly greater reductions compared with doubling the statin dose in LDL-C (26.2% vs 17.9%, p = 0.0026 and total cholesterol (20.8% vs 12.2%, p = 0.0003. Percentage of patients achieving treatment goal was greater for statin + ezetimibe (58.6% vs doubling statin (41.2%, but the difference was not statistically significant (p = 0.1675. The safety and tolerability profiles were similar between treatments. Conclusion Ezetimibe added to ongoing statin therapy resulted in significantly greater lipid-lowering compared with doubling the dose of statin in Taiwanese patients with hypercholesterolemia. Studies to assess clinical outcome benefit are ongoing. Trial registration Registered at ClinicalTrials.gov: NCT00652327

  7. Pharmacokinetic interaction of finasteride with tamsulosin hydrochloride: an open-label, randomized, 3-period crossover study in healthy Chinese male volunteers.

    Science.gov (United States)

    Chu, Nannan; Xu, Hongrong; Wang, Guoqin; Wang, Jiangdian; Chen, Weili; Yuan, Fei; Yang, Mengjie; Li, Xuening

    2015-02-01

    The primary aim of this study was to evaluate whether there was clinically significant pharmacokinetic (PK) interaction between finasteride and tamsulosin in healthy Chinese male subjects. This was an open-label, randomized, 3-period, crossover study. Subjects received single and multiple doses of 5 mg finasteride alone, single and multiple doses of 0.2 mg tamsulosin hydrochloride sustained-release capsule alone, and single and multiple doses of 5 mg finasteride with 0.2 mg tamsulosin hydrochloride, in an order determined by a computerized randomization schedule. Blood samples were collected up to 48 hours after dosing on study day 1 and up to 24 hours after dosing on study day 9 for determination of plasma concentrations with a validated LC-MS/MS method. Pharmacokinetic parameters were estimated via noncompartmental methods. Tolerability was evaluated by monitoring adverse events, laboratory assays, vital signs, and 12-lead ECG. Fifteen subjects were enrolled, and 14 completed the study. The geometric mean ratios (GMRs) (90% CIs) of AUC(τ,ss) and C(max,ss) values of finasteride at steady state between coadministration of finasteride and tamsulosin hydrochloride and finasteride alone were 1.14 (1.05-1.23) and 1.06 (0.99-1.14), respectively. The GMRs (90% CIs) for AUC(0-t) and C(max) values of finasteride for a single dose of coadministration of finasteride and tamsulosin hydrochloride and finasteride alone were 1.02 (0.94-1.11) and 1.06 (1.01-1.11), respectively. The GMRs (90% CIs) for AUC(τ,ss) and C(max,ss) values of tamsulosin at steady-state for coadministration of finasteride and tamsulosin hydrochloride and tamsulosin hydrochloride alone were 1.18 (1.05-1.33) and 1.23 (1.06-1.43), respectively. The GMRs (90% CIs) for AUC(0-t) and C(max) values of tamsulosin for a single dose of coadministration of finasteride and tamsulosin hydrochloride and tamsulosin hydrochloride alone were 1.04 (0.97-1.10) and 1.04 (0.98-1.11), respectively. Statistical analyses

  8. Perfusion by Arterial Spin labelling following Single dose Tadalafil In Small vessel disease (PASTIS)

    DEFF Research Database (Denmark)

    Pauls, Mathilde M H; Clarke, Natasha; Trippier, Sarah

    2017-01-01

    vascular territories. The aim of this trial is to test the hypothesis that tadalafil increases cerebral blood flow in older people with small vessel disease. METHODS/DESIGN: Perfusion by Arterial Spin labelling following Single dose Tadalafil In Small vessel disease (PASTIS) is a phase II randomised double......-blind crossover trial. In two visits, 7-30 days apart, participants undergo arterial spin labelling to measure cerebral blood flow and a battery of cognitive tests, pre- and post-dosing with oral tadalafil (20 mg) or placebo. SAMPLE SIZE: 54 participants are required to detect a 15% increase in cerebral blood...

  9. Single-dose intravenous iron infusion or oral iron for treatment of fatigue after postpartum haemorrhage

    DEFF Research Database (Denmark)

    Holm, C; Thomsen, L L; Norgaard, A

    2017-01-01

    BACKGROUND AND OBJECTIVES: To evaluate the clinical efficacy of a single-dose intravenous infusion of iron isomaltoside compared with current treatment practice with oral iron measured by physical fatigue in women after postpartum haemorrhage. MATERIALS AND METHODS: Single-centre, open-label, ran......BACKGROUND AND OBJECTIVES: To evaluate the clinical efficacy of a single-dose intravenous infusion of iron isomaltoside compared with current treatment practice with oral iron measured by physical fatigue in women after postpartum haemorrhage. MATERIALS AND METHODS: Single-centre, open...

  10. Regulatory T Cell Responses in Participants with Type 1 Diabetes after a Single Dose of Interleukin-2: A Non-Randomised, Open Label, Adaptive Dose-Finding Trial

    Science.gov (United States)

    Todd, John A.; Porter, Linsey; Smyth, Deborah J.; Rainbow, Daniel B.; Ferreira, Ricardo C.; Yang, Jennie H.; Bell, Charles J. M.; Schuilenburg, Helen; Challis, Ben; Clarke, Pamela; Coleman, Gillian; Dawson, Sarah; Goymer, Donna; Kennet, Jane; Brown, Judy; Greatorex, Jane; Goodfellow, Ian; Evans, Mark; Mander, Adrian P.; Bond, Simon; Wicker, Linda S.

    2016-01-01

    Background Interleukin-2 (IL-2) has an essential role in the expansion and function of CD4+ regulatory T cells (Tregs). Tregs reduce tissue damage by limiting the immune response following infection and regulate autoreactive CD4+ effector T cells (Teffs) to prevent autoimmune diseases, such as type 1 diabetes (T1D). Genetic susceptibility to T1D causes alterations in the IL-2 pathway, a finding that supports Tregs as a cellular therapeutic target. Aldesleukin (Proleukin; recombinant human IL-2), which is administered at high doses to activate the immune system in cancer immunotherapy, is now being repositioned to treat inflammatory and autoimmune disorders at lower doses by targeting Tregs. Methods and Findings To define the aldesleukin dose response for Tregs and to find doses that increase Tregs physiologically for treatment of T1D, a statistical and systematic approach was taken by analysing the pharmacokinetics and pharmacodynamics of single doses of subcutaneous aldesleukin in the Adaptive Study of IL-2 Dose on Regulatory T Cells in Type 1 Diabetes (DILT1D), a single centre, non-randomised, open label, adaptive dose-finding trial with 40 adult participants with recently diagnosed T1D. The primary endpoint was the maximum percentage increase in Tregs (defined as CD3+CD4+CD25highCD127low) from the baseline frequency in each participant measured over the 7 d following treatment. There was an initial learning phase with five pairs of participants, each pair receiving one of five pre-assigned single doses from 0.04 × 106 to 1.5 × 106 IU/m2, in order to model the dose-response curve. Results from each participant were then incorporated into interim statistical modelling to target the two doses most likely to induce 10% and 20% increases in Treg frequencies. Primary analysis of the evaluable population (n = 39) found that the optimal doses of aldesleukin to induce 10% and 20% increases in Tregs were 0.101 × 106 IU/m2 (standard error [SE] = 0.078, 95% CI = −0

  11. Effects of food intake on the pharmacokinetics of diclofenac potassium soft gelatin capsules: a single-dose, randomized, two-way crossover study.

    Science.gov (United States)

    Scallion, Ralph; Moore, Keith A

    2009-10-01

    Diclofenac potassium liquid-filled soft gelatin capsule (DPSGC) is an investigational formulation that uses dispersing agents designed to facilitate rapid and consistent absorption of this NSAID. The aim of this study was to characterize the effects of food intake on the pharmacokinetic (PK) profile of oral DPSGC at doses of 25 and 50 mg. In this open-label, randomized, single-dose (2 distinct doses), 2-way crossover bioavailability study, healthy adult volunteers were randomly assigned to receive a single dose of DPSGC 25 or 50 mg after an overnight fast (fasted condition) or high-fat breakfast (fed condition) (period 1). After 7 days, the participants received the same dose under the opposite fed/fasted condition (period 2). Serial blood samples were obtained before and through 6 hours after study drug administration. Concentrations of diclofenac in plasma were determined using HPLC, and PK profiles were studied using ANCOVA. Adverse events (AEs) were monitored and recorded on each in-clinic day. Of 47 participants included in the study, 24 received the 25-mg dose of DPSGC and 23 received the 50-mg dose. The majority of participants were male (80.9%), and the mean age was 28.6 years. The mean (SD) AUC values for the fasted and fed states were 691 (195) and 680 (184) ng x h/mL, respectively, with the 25-mg dose, and 1521 (377) and 1416 (366) ng . h/mL, respectively, with the 50-mg dose, suggesting that the extent of absorption was similar with both dietary conditions at each dose. Food intake was associated with decreases in C(max) by nearly half in the 25-mg group (fasted vs fed, 1156 [482] vs 686 [411] ng/mL, respectively; P < 0.05) and the 50-mg group (2365 [1034] vs 1154 [592 ng/mL; P < 0.05) and delayed T(max) in the 25-mg group (0.49 [0.16] vs 1.02 [0.55] hours; P < 0.05) and 50-mg group (0.51 [0.19] vs 1.28 [0.71] hours; P < 0.05). Two mild AEs (nasal congestion and light-headedness) were reported in 2 participants who received 25 mg under fed conditions

  12. Single-dose, subcutaneous recombinant phenylalanine ammonia lyase conjugated with polyethylene glycol in adult patients with phenylketonuria: an open-label, multicentre, phase 1 dose-escalation trial.

    Science.gov (United States)

    Longo, Nicola; Harding, Cary O; Burton, Barbara K; Grange, Dorothy K; Vockley, Jerry; Wasserstein, Melissa; Rice, Gregory M; Dorenbaum, Alejandro; Neuenburg, Jutta K; Musson, Donald G; Gu, Zhonghua; Sile, Saba

    2014-07-05

    Phenylketonuria is an inherited disease caused by impaired activity of phenylalanine hydroxylase, the enzyme that converts phenylalanine to tyrosine, leading to accumulation of phenylalanine and subsequent neurocognitive dysfunction. Phenylalanine ammonia lyase is a prokaryotic enzyme that converts phenylalanine to ammonia and trans-cinnamic acid. We aimed to assess the safety, tolerability, pharmacokinetic characteristics, and efficacy of recombinant Anabaena variabilis phenylalanine ammonia lyase (produced in Escherichia coli) conjugated with polyethylene glycol (rAvPAL-PEG) in reducing phenylalanine concentrations in adult patients with phenylketonuria. In this open-label, phase 1, multicentre trial, single subcutaneous injections of rAvPAL-PEG were given in escalating doses (0·001, 0·003, 0·010, 0·030, and 0·100 mg/kg) to adults with phenylketonuria. Participants aged 18 years or older with blood phenylalanine concentrations of 600 μmol/L or higher were recruited from among patients attending metabolic disease clinics in the USA. The primary endpoints were safety and tolerability of rAvPAL-PEG. Secondary endpoints were the pharmacokinetic characteristics of the drug and its effect on concentrations of phenylalanine. Participants and investigators were not masked to assigned dose group. This study is registered with ClinicalTrials.gov, number NCT00925054. 25 participants were recruited from seven centres between May 6, 2008, and April 15, 2009, with five participants assigned to each escalating dose group. All participants were included in the safety population. The most frequently reported adverse events were injection-site reactions and dizziness, which were self-limited and without sequelae. Two participants had serious adverse reactions to intramuscular medroxyprogesterone acetate, a drug that contains polyethylene glycol as an excipient. Three of five participants given the highest dose of rAvPAL-PEG (0·100 mg/kg) developed a generalised skin rash

  13. Microbial contamination of single-and multiple-dose vials after opening in a pulmonary teaching hospital

    Directory of Open Access Journals (Sweden)

    Shadi Baniasadi

    Full Text Available OBJECTIVES: Intravenous therapy is a complex procedure usually requiring the preparation of the medication in the clinical area before administration to the patient. Breaches in aseptic technique may result in microbial contaminations of vials which is a potential cause of different avoidable infections. We aimed to investigate the prevalence and pattern of microbial contamination of single- and multiple-dose vials in the largest pulmonary teaching hospital in Iran. METHODS: In a period of 2 months, opened single- and multiple-dose vials from different wards were sampled by a pharmacist. The name of the medication, ward, labeling of the vials, the date of opening, and storing temperature were recorded for each vial. Remained contents of each vial were cultured using appropriate bacterial and fungal growth media. RESULTS: Microbial contamination was identified in 11 of 205 (5.36% of vials. The highest contamination rate was 14.28% for vials used in interventional bronchoscopy unit. The most frequent contaminated medication was insulin. Gram-positive bacteria (81.82% were more significantly involved than gram-negative ones (9.09% and fungi (9.09%, with the highest frequency for Staphylococcus epidermidis . CONCLUSIONS: Our data demonstrate that repeated use of vials especially if basic sterility measures are disobeyed can cause microbial contamination of administered products to the patients. Infection preventionists are responsible to train health care workers regarding aseptic techniques and apply guidelines for aseptic handling of intravenous solutions.

  14. Microbial contamination of single-and multiple-dose vials after opening in a pulmonary teaching hospital

    Directory of Open Access Journals (Sweden)

    Shadi Baniasadi

    2013-02-01

    Full Text Available OBJECTIVES: Intravenous therapy is a complex procedure usually requiring the preparation of the medication in the clinical area before administration to the patient. Breaches in aseptic technique may result in microbial contaminations of vials which is a potential cause of different avoidable infections. We aimed to investigate the prevalence and pattern of microbial contamination of single- and multiple-dose vials in the largest pulmonary teaching hospital in Iran. METHODS: In a period of 2 months, opened single- and multiple-dose vials from different wards were sampled by a pharmacist. The name of the medication, ward, labeling of the vials, the date of opening, and storing temperature were recorded for each vial. Remained contents of each vial were cultured using appropriate bacterial and fungal growth media. RESULTS: Microbial contamination was identified in 11 of 205 (5.36% of vials. The highest contamination rate was 14.28% for vials used in interventional bronchoscopy unit. The most frequent contaminated medication was insulin. Gram-positive bacteria (81.82% were more significantly involved than gram-negative ones (9.09% and fungi (9.09%, with the highest frequency for Staphylococcus epidermidis . CONCLUSIONS: Our data demonstrate that repeated use of vials especially if basic sterility measures are disobeyed can cause microbial contamination of administered products to the patients. Infection preventionists are responsible to train health care workers regarding aseptic techniques and apply guidelines for aseptic handling of intravenous solutions.

  15. Simvastatin as an Adjunct to Conventional Therapy of Non-infectious Uveitis: A Randomized, Open-Label Pilot Study.

    Science.gov (United States)

    Shirinsky, Ivan V; Biryukova, Anastasia A; Shirinsky, Valery S

    2017-12-01

    Statins have been shown to reduce ocular inflammation in animal models of uveitis and to prevent development of uveitis in observational studies. There have been no experimental human studies evaluating statins' efficacy and safety in uveitis. In this study, we aimed to investigate efficacy and safety of simvastatin in patients with uveitis. For this single-center, open-label, randomized study, we enrolled patients with acute non-infectious uveitis. The patients were randomized to receive 40 mg simvastatin per day for 2 months in addition to conventional treatment or conventional treatment alone. The studied outcomes were the rate of steroid-sparing control of ocular inflammation, measures of ocular inflammation, intraocular pressure, and visual acuity. Fifty patients were enrolled in the study. Twenty-five patients were randomly assigned to receive simvastatin with conventional treatment and 25 to conventional treatment alone. Simvastatin was associated with significantly higher rates of steroid-sparing ocular inflammation control, decrease in anterior chamber inflammation, and improvement in visual acuity. The treatment was well tolerated, no serious adverse effects were observed. Our findings suggest that statins may have therapeutic potential in uveitis. These results need to be confirmed in double-blind, randomized, controlled studies.

  16. Open-label placebo treatment in chronic low back pain: a randomized controlled trial.

    Science.gov (United States)

    Carvalho, Cláudia; Caetano, Joaquim Machado; Cunha, Lidia; Rebouta, Paula; Kaptchuk, Ted J; Kirsch, Irving

    2016-12-01

    This randomized controlled trial was performed to investigate whether placebo effects in chronic low back pain could be harnessed ethically by adding open-label placebo (OLP) treatment to treatment as usual (TAU) for 3 weeks. Pain severity was assessed on three 0- to 10-point Numeric Rating Scales, scoring maximum pain, minimum pain, and usual pain, and a composite, primary outcome, total pain score. Our other primary outcome was back-related dysfunction, assessed on the Roland-Morris Disability Questionnaire. In an exploratory follow-up, participants on TAU received placebo pills for 3 additional weeks. We randomized 97 adults reporting persistent low back pain for more than 3 months' duration and diagnosed by a board-certified pain specialist. Eighty-three adults completed the trial. Compared to TAU, OLP elicited greater pain reduction on each of the three 0- to 10-point Numeric Rating Scales and on the 0- to 10-point composite pain scale (P Pain reduction on the composite Numeric Rating Scales was 1.5 (95% confidence interval: 1.0-2.0) in the OLP group and 0.2 (-0.3 to 0.8) in the TAU group. Open-label placebo treatment also reduced disability compared to TAU (P pain (1.5, 0.8-2.3) and disability (3.4, 2.2-4.5). Our findings suggest that OLP pills presented in a positive context may be helpful in chronic low back pain.

  17. Open-label trial and randomized, double-blind, placebo-controlled, crossover trial of hydrogen-enriched water for mitochondrial and inflammatory myopathies

    Directory of Open Access Journals (Sweden)

    Ito Mikako

    2011-10-01

    Full Text Available Abstract Background Molecular hydrogen has prominent effects on more than 30 animal models especially of oxidative stress-mediated diseases and inflammatory diseases. In addition, hydrogen effects on humans have been reported in diabetes mellitus type 2, hemodialysis, metabolic syndrome, radiotherapy for liver cancer, and brain stem infarction. Hydrogen effects are ascribed to specific radical-scavenging activities that eliminate hydroxyl radical and peroxynitrite, and also to signal-modulating activities, but the detailed molecular mechanisms still remain elusive. Hydrogen is a safe molecule that is largely produced by intestinal bacteria in rodents and humans, and no adverse effects have been documented. Methods We performed open-label trial of drinking 1.0 liter per day of hydrogen-enriched water for 12 weeks in five patients with progressive muscular dystrophy (PMD, four patients with polymyositis/dermatomyositis (PM/DM, and five patients with mitochondrial myopathies (MM, and measured 18 serum parameters as well as urinary 8-isoprostane every 4 weeks. We next conducted randomized, double-blind, placebo-controlled, crossover trial of 0.5 liter per day of hydrogen-enriched water or placebo water for 8 weeks in 10 patients with DM and 12 patients with MM, and measured 18 serum parameters every 4 weeks. Results In the open-label trial, no objective improvement or worsening of clinical symptoms was observed. We, however, observed significant effects in lactate-to-pyruvate ratios in PMD and MM, fasting blood glucose in PMD, serum matrix metalloproteinase-3 (MMP3 in PM/DM, and serum triglycerides in PM/DM. In the double-blind trial, no objective clinical effects were observed, but a significant improvement was detected in lactate in MM. Lactate-to-pyruvate ratios in MM and MMP3 in DM also exhibited favorable responses but without statistical significance. No adverse effect was observed in either trial except for hypoglycemic episodes in an insulin

  18. Atomoxetine Open-Label Trial in ADHD

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    J Gordon Millichap

    2002-07-01

    Full Text Available Atomoxetine (originally named tomoxetine, a new therapy for attention deficit hyperactivity disorder (ADHD marketed by Eli Lilly, was compared to methylphenidate in a prospective, randomized, open-label study for 10 weeks duration, at the University of Nebraska Medical Center, Massachusetts General Hospital, Mount Sinai Medical Center, Carolinas Medical Center, and Lilly Research Laboratories.

  19. A Phase Ib open label, randomized, safety study of SANGUINATE™ in patients with sickle cell anemia

    Directory of Open Access Journals (Sweden)

    Hemant Misra

    Full Text Available Abstract Background: Treatment of sickle cell anemia is a challenging task and despite the well understood genetic and biochemical pathway of sickle hemoglobin, current therapy continues to be limited to the symptomatic treatment of pain, supplemental oxygen, antibiotics, red blood cell transfusions and hydroxyurea. SANGUINATE is a carbon monoxide releasing molecule and oxygen transfer agent under clinical development for the treatment of sickle cell anemia and comorbidities. Methods: An open-label randomized Phase Ib study was performed in adult sickle cell anemia patients. Two dose levels of SANGUINATE were compared to hydroxyurea in 24 homozygotes for Hb SS. Twelve subjects received either a low dose (160 mg/kg of SANGUINATE or 15 mg/kg hydroxyurea. Another 12 subjects received either a high dose (320 mg/kg of SANGUINATE or 15 mg/kg hydroxyurea. The primary endpoint was the safety of SANGUINATE versus hydroxyurea in sickle cell anemia patients. Secondary endpoints included determination of the plasma pharmacokinetics and assessment of hematologic measurements. Results: Musculoskeletal related adverse events were the most common. Transient troponin I levels increased in three patients, one of whom had an increase in tricuspid regurgitant velocity; however, no clinical signs were noted. Following an assessment of vital signs, tricuspid regurgitant velocity, electrocardiogram, serum biochemistry, hematology, urinalysis, and analysis of reported adverse events, SANGUINATE was found to be safe in stable sickle cell anemia patients. Conclusions: The clinical trial met its primary objective of demonstrating an acceptable safety profile for SANGUINATE in patients with sickle cell anemia. This trial established the safety of SANGUINATE at both dose levels and permitted its advance to Phase II trials.

  20. Immunogenicity and safety of high-dose hepatitis B vaccine among drug users: A randomized, open-labeled, blank-controlled trial.

    Science.gov (United States)

    Feng, Yongliang; Shi, Jing; Gao, Linying; Yao, Tian; Feng, Dan; Luo, Dan; Li, Zhansheng; Zhang, Yawei; Wang, Fuzhen; Cui, Fuqiang; Li, Li; Liang, Xiaofeng; Wang, Suping

    2017-06-03

    Due to the low uptake, adherence, and completion of vaccination among drug users, and their compromised immune responses to hepatitis B vaccination, the current practice of hepatitis B vaccination may not provide optimal protection. The aim of this study was to evaluate the immunogenicity and safety of 60 µg and 20 µg hepatitis B vaccines among drug users. A randomized, open-labeled, blank-controlled trial was conducted among drug users at 2 drug rehabilitation centers in China. The eligible participants were drug users who were serologically negative for the hepatitis B surface antigen (HBsAg) and the hepatitis B surface antibody (anti-HBs). Participants were randomized in a ratio of 1:1:1 to receive 20 µg (IM20 group) or 60 µg (IM60 group) of hepatitis B vaccine or blank control at months 0, 1, and 6, and followed at months 6, 7, and 12. Seroconversion rates of 94.7% and 92.6% were observed in IM20 and IM60 groups at month 7, and correspondingly decreased to 89.5% and 91.7% respectively at month 12. The IM60 group showed significantly higher geometric mean concentrations (GMCs) of anti-HBs (2022.5 and 676.7 mIU mL-1) than the IM20 group did (909.6 and 470.5 mIU mL-1) at months 7 and 12 (P B vaccines showed good immunogenicity among the drug users.

  1. The Influence of Hepatic and Renal Impairment on the Pharmacokinetics of a Treatment for Herpes Zoster, Amenamevir (ASP2151): Phase 1, Open-Label, Single-Dose, Parallel-Group Studies.

    Science.gov (United States)

    Kusawake, Tomohiro; Kowalski, Donna; Takada, Akitsugu; Kato, Kota; Katashima, Masataka; Keirns, James J; Lewand, Michaelene; Lasseter, Kenneth C; Marbury, Thomas C; Preston, Richard A

    2017-12-01

    Amenamevir (ASP2151) is a nonnucleoside human herpesvirus helicase-primase inhibitor that was approved in Japan for the treatment of herpes zoster (shingles) in 2017. This article reports the results of two clinical trials that investigated the effects of renal and hepatic impairment on the pharmacokinetics of amenamevir. These studies were phase 1, open-label, single-dose (oral 400 mg), parallel-group studies evaluating the pharmacokinetics, safety, and tolerability of amenamevir in healthy participants and participants with moderate hepatic impairment and mild, moderate, and severe renal impairment. In the hepatic impairment study, the pharmacokinetic profile of amenamevir in participants with moderate hepatic impairment was generally similar to that of participants with normal hepatic function. In the renal impairment study, the area under the amenamevir concentration versus time curve from the time of dosing up to the time of the last sample with extrapolation to infinity of the terminal phase was increased by 78.1% in participants with severe renal impairment. There was a positive relationship between creatinine clearance and oral and renal clearance for amenamevir in the renal impairment study. In both studies, amenamevir was safe and well tolerated. The findings of the hepatic impairment study indicate that no dosing adjustment is required in patients with moderate hepatic impairment. In the renal impairment study, systemic amenamevir exposure was increased by renal impairment. However, it is unlikely that renal impairment will have a significant effect on the safety of amenamevir given that in previous pharmacokinetic and safety studies in healthy individuals amenamevir was safe and well tolerated after a single dose (5-2400 mg, fasted condition) and repeated doses for 7 days (300 or 600 mg, fed condition), and the amount of amenamevir exposure in the renal impairment study was covered by those studies. These findings suggest that amenamevir does not

  2. A prospective, open-label study of low-dose total skin electron beam therapy in mycosis fungoides

    DEFF Research Database (Denmark)

    Kamstrup, Maria R; Specht, Lena; Skovgaard, Gunhild L

    2008-01-01

    causes and did not complete treatment. Acute side effects included desquamation, xerosis, and erythema of the skin. No severe side effects were observed. CONCLUSION: Low-dose total skin electron beam therapy can induce complete and partial responses in Stage IB-II mycosis fungoides; however, the duration......PURPOSE: To determine the effect of low-dose (4 Gy) total skin electron beam therapy as a second-line treatment of Stage IB-II mycosis fungoides in a prospective, open-label study. METHODS AND MATERIALS: Ten patients (6 men, 4 women, average age 68.7 years [range, 55-82 years......]) with histopathologically confirmed mycosis fungoides T2-T4 N0-N1 M0 who did not achieve complete remission or relapsed within 4 months after treatment with psoralen plus ultraviolet-A were included. Treatment consisted of low-dose total skin electron beam therapy administered at a total skin dose of 4 Gy given in 4...

  3. Comparison between IV immune globulin (IVIG) and anti-D globulin for treatment of immune thrombocytopenia: a randomized open-label study.

    Science.gov (United States)

    Eghbali, Aziz; Azadmanesh, Peyman; Bagheri, Bahador; Taherahmadi, Hasan; Sadeghi Sedeh, Bahman

    2016-08-01

    To compare the effect of IV immune globulin (IVIG) and anti-D globulin (anti-D) for treatment of immune thrombocytopenia (ITP) in children. A randomized, open-label, single-center clinical trial was carried out in Amir-Kabir Hospital (Arak, Iran). The study was performed on 60 children with acute and chronic ITP, aged from 1 to 15 years. Patients were randomly assigned (1:1) to 50 μg/kg anti-D or 1 g/kg IVIG. Platelet counting was performed at baseline and at 3, 7, and 14 days after treatment termination. Safety assessment was performed in all patients. Anti-D caused a quicker response on the 3rd day of treatment (P anti-D had lower rate of side effects including fever (P anti-D was associated with rapid rise of platelets compared to IVIG. In addition, anti-D treatment had acceptable safety profile. © 2016 Société Française de Pharmacologie et de Thérapeutique.

  4. Comparative bioavailability and pharmacokinetics of two oral formulations of flurbiprofen: a single-dose, randomized, open-label, two-period, crossover study in Pakistani subjects.

    Science.gov (United States)

    Qayyum, Aisha; Najmi, Muzammil Hasan; Abbas, Mateen

    2013-11-01

    Comparative bioavailability studies are conducted to establish the bioequivalence of generic formulation with that of branded reference formulation, providing confidence to clinicians to use these products interchangeably. This study was carried out to compare a locally manufactured formulation of flurbiprofen with that of a branded product. Twenty two healthy male adults received a single dose of flurbiprofen (100mg) either generic or branded product according to randomization scheme on each of 2 periods. Blood samples were collected and plasma flurbiprofen concentration was determined by a validated HPLC method. Pharmacokinetic parameters like AUC(0-t), AUC(0-oo), Cmax, Tmax, t½, Vd and clearance were determined. The 90% CI for the ratio of geometric means of test to reference product's pharmacokinetic variables was calculated. Pharmacokinetic parameters for two formulations were comparable. Ratio of means of AUC(0-24), AUC(0-oo) and Cmax for test to reference products and 90% CI for these ratios were within the acceptable range. The p-values calculated by TOST were much less than the specified value (p-0.05). ANOVA gave p-values which were more than the specified value (p-0.05) for sequence, subject, period and formulation. Test formulation of flurbiprofen (tablet Flurso) was found to meet the criteria for bioequivalence to branded product (tablet Ansaid) based on pharmacokinetic parameters.

  5. Effervescent N-Acetylcysteine Tablets versus Oral Solution N-Acetylcysteine in Fasting Healthy Adults: An Open-Label, Randomized, Single-Dose, Crossover, Relative Bioavailability Study

    Directory of Open Access Journals (Sweden)

    Spencer C. Greene, MD, FACEP, FACMT

    2016-01-01

    Conclusions: Data from this study of a single dose of 11 g oral NAC demonstrated that effervescent NAC tablets and oral solution NAC met the regulatory criteria for bioequivalence in fasting healthy adult subjects. Effervescent NAC tablets appear to be a more palatable alternative for treatment of acetaminophen overdose. ClinicalTrials.gov identifier: NCT02723669.

  6. Immunogenicity and safety of a single dose of a CRM-conjugated meningococcal ACWY vaccine in children and adolescents aged 2-18 years in Taiwan: results of an open label study.

    Science.gov (United States)

    Huang, Li-Min; Chiu, Nan-Chang; Yeh, Shu-Jen; Bhusal, Chiranjiwi; Arora, Ashwani Kumar

    2014-09-08

    MenACWY-CRM (Menveo®, Novartis Vaccines, Siena, Italy) is a quadrivalent meningococcal conjugate vaccine developed to help prevent invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, W, and Y. It is approved within the European Union in persons >2 years of age and in persons from 2 months to 55 years of age in the United States, among other countries. Little is known about the immunogenicity and safety of this vaccine in Taiwanese children >2 years and adolescents. This study assessed the immunogenicity and safety of a single injection of MenACWY-CRM vaccine in Taiwanese subjects aged 2-18 years old. In this phase III, multicentre, open-label study 341 subjects received one dose of MenACWY-CRM. Immunogenicity measures were rates of seroresponse (defined as the proportion of subjects with a postvaccination hSBA ≥1:8 if the prevaccination (baseline) titre was CRM vaccination at Day 29 for the serogroups A, C, W, and Y were 83%, 93%, 50%, and 65%, respectively. At Day 29 the percentages of subjects with hSBA ≥1:8 against all four serogroups A, C, W and Y were: 83%, 96%, 96% and 82%, respectively. GMTs against all serogroups rose by ≥7-fold from baseline to Day 29. The vaccine was well tolerated. A single dose of MenACWY-CRM demonstrated a robust immune response, and an acceptable safety profile in Taiwanese children and adolescents. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Bioequivalence and pharmacokinetic evaluation of two formulations of risperidone 2 mg : an open-label, single-dose, fasting, randomized-sequence, two-way crossover study in healthy male Chinese volunteers.

    Science.gov (United States)

    Liu, Yun; Zhang, Meng-qi; Jia, Jing-ying; Liu, Yan-mei; Liu, Gang-yi; Li, Shui-jun; Wang, Wei; Weng, Li-ping; Yu, Chen

    2013-03-01

    Risperidone is a benzisoxazole derivate and is effective in the treatment of schizophrenia and other psychiatric illnesses in adults and children. Although there are a few reports in the literature regarding the pharmacokinetic characteristics of risperidone, insufficient data on its pharmacokinetic properties in a Chinese population are available. To meet the requirements for marketing a new generic product, this study was designed to compare the pharmacokinetic properties and bioequivalence of two 2 mg tablet formulations of risperidone: a newly developed generic formulation (test) and a branded formulation (reference) in healthy adult male Chinese volunteers. A single-dose, open-label, randomized-sequence, 2 × 2 crossover study was conducted in fasted healthy male Chinese volunteers. Eligible participants were randomly assigned in a 1:1 ratio to receive 1 tablet (2 mg each) of the test formulation (Risperidone tablet; Dr. Reddy's Laboratories Ltd., Hyderabad, India) or the reference formulation (Risperdal(®) tablet; Xian-Janssen Pharmaceutical Ltd., Xi-an, China), followed by a 2-week washout period and subsequent administration of the alternate formulation. The study drugs were administered after a 10-hour overnight fast. Plasma samples were collected over 96 hours. Plasma concentrations of the parent drug, risperidone, and its active metabolite, 9-hydroxy-risperidone, were analyzed by a liquid chromatography-tandem mass spectrometry method. The formulations would be considered bioequivalent if the 90% confidence intervals (CIs) of the natural log-transformed values were within the predetermined 80-125% equivalence range for the maximum plasma drug concentration (Cmax) and the area under the plasma concentration-time curve (AUC), in accordance with guidelines issued by the US Food and Drug Administration. Assessment of tolerability was based on recording of adverse events (AEs), monitoring of vital signs, electrocardiograms, and laboratory tests at baseline

  8. An Open-Label Trial of Escitalopram in Pervasive Developmental Disorders.

    Science.gov (United States)

    Owley, Thomas; Walton, Laura; Salt, Jeff; Guter, Stephen J., Jr.; Winnega, Marrea; Leventhal, Bennett L.; Cook, Edwin H., Jr.

    2005-01-01

    Objective: To assess the effect of escitalopram in the treatment of pervasive developmental disorders (PDDs). Method: This 10-week study had a forced titration, open-label design. Twenty-eight subjects (mean age 125.1 [+ or -] 33.5 months) with a PDD received escitalopram at a dose that increased weekly to a maximum dose of 20 mg as tolerated. The…

  9. Adjunctive low-dose docosahexaenoic acid (DHA) for major depression: An open-label pilot trial.

    Science.gov (United States)

    Smith, Deidre J; Sarris, Jerome; Dowling, Nathan; O'Connor, Manjula; Ng, Chee H

    2018-04-01

    Whilst the majority of evidence supports the adjunctive use of eicosapentaenoic acid (EPA) in improving mood, to date no study exists using low-dose docosahexaenoic acid (DHA) alone as an adjunctive treatment in patients with mild to moderate major depressive disorder (MDD). A naturalistic 8-week open-label pilot trial of low-dose DHA, (260 mg or 520 mg/day) in 28 patients with MDD who were non-responsive to medication or psychotherapy, with a Hamilton Depression Rating Scale (HAM-D) score of greater than 17, was conducted. Primary outcomes of depression, clinical severity, and daytime sleepiness were measured. After 8 weeks, 54% of patients had a ≥50% reduction on the HAM-D, and 45% were in remission (HAM-D ≤ 7). The eta-squared statistic (0.59) indicated a large effect size for the reduction of depression (equivalent to Cohen's d of 2.4). However confidence in this effect size is tempered due to the lack of a placebo. The mean score for the Clinical Global Impression Severity Scale was significantly improved by 1.28 points (P depression.

  10. Piroxicam immediate release formulations: A fasting randomized open-label crossover bioequivalence study in healthy volunteers.

    Science.gov (United States)

    Helmy, Sally A; El-Bedaiwy, Heba M

    2014-11-01

    Piroxicam is a NSAID with analgesic and antipyretic properties, used for the treatment of rheumatoid diseases. The aim of this study was to evaluate the bioequivalence of two brands of piroxicam capsules (20 mg) in 24 Egyptian volunteers. The in vivo study was established according to a single-center, randomized, single-dose, laboratory-blinded, 2-period, 2-sequence, crossover study with a washout period of 3 weeks. Under fasting conditions, 24 healthy male volunteers were randomly selected to receive a single oral dose of one capsule (20 mg) of either test or reference product. Plasma samples were obtained over a 144-hour interval and analyzed for piroxicam by HPLC with UV detection. The pharmacokinetic parameters Cmax , tmax , AUC0-t , AUC0-∞ , Vd /F, Cl/F, and t1/2 were determined from plasma concentration-time profiles. The 90% confidence intervals for the ratio of log transformed values of Cmax , AUC0-t , and AUC0-∞ of the two treatments were within the acceptable range (0.8-1.25) for bioequivalence. From PK perspectives, the two piroxicam formulations were considered bioequivalent, based on the rate and extent of absorption. No adverse events occurred or were reported after a single 20-mg piroxicam and both formulations were well-tolerated. © 2014, The American College of Clinical Pharmacology.

  11. Assessment of strategies for switching patients from olanzapine to risperidone: A randomized, open-label, rater-blinded study

    Directory of Open Access Journals (Sweden)

    Berry Sally A

    2008-06-01

    Full Text Available Abstract Background In clinical practice, physicians often need to change the antipsychotic medications they give to patients because of an inadequate response or the presence of unacceptable or unsafe side effects. However, there is a lack of consensus in the field as to the optimal switching strategy for antipsychotics, especially with regards to the speed at which the dose of the previous antipsychotic should be reduced. This paper assesses the short-term results of strategies for the discontinuation of olanzapine when initiating risperidone. Methods In a 6-week, randomized, open-label, rater-blinded study, patients with schizophrenia or schizoaffective disorder, on a stable drug dose for more than 30 days at entry, who were intolerant of or exhibiting a suboptimal symptom response to more than 30 days of olanzapine treatment, were randomly assigned to the following switch strategies (common risperidone initiation scheme; varying olanzapine discontinuation: (i abrupt strategy, where olanzapine was discontinued at risperidone initiation; (ii gradual 1 strategy, where olanzapine was given at 50% entry dose for 1 week after risperidone initiation and then discontinued; or (iii gradual 2 strategy, where olanzapine was given at 100% entry dose for 1 week, then at 50% in the second week, and then discontinued. Results The study enrolled 123 patients on stable doses of olanzapine. Their mean age was 40.3 years and mean (± standard deviation (SD baseline Positive and Negative Syndrome Scale (PANSS total score of 75.6 ± 11.5. All-cause treatment discontinuation was lowest (12% in the group with the slowest olanzapine dose reduction (gradual 2 and occurred at half the discontinuation rate in the other two groups (25% in abrupt and 28% in gradual 1. The relative risk of early discontinuation was 0.77 (confidence interval 0.61–0.99 for the slowest dose reduction compared with the other two strategies. After the medication was changed, improvements at

  12. Efficacy of Single-Dose and Triple-Dose Albendazole and Mebendazole against Soil-Transmitted Helminths and Taenia spp.: A Randomized Controlled Trial

    Science.gov (United States)

    Steinmann, Peter; Utzinger, Jürg; Du, Zun-Wei; Jiang, Jin-Yong; Chen, Jia-Xu; Hattendorf, Jan; Zhou, Hui; Zhou, Xiao-Nong

    2011-01-01

    Background The control of soil-transmitted helminth (STH) infections currently relies on the large-scale administration of single-dose oral albendazole or mebendazole. However, these treatment regimens have limited efficacy against hookworm and Trichuris trichiura in terms of cure rates (CR), whereas fecal egg reduction rates (ERR) are generally high for all common STH species. We compared the efficacy of single-dose versus triple-dose treatment against hookworm and other STHs in a community-based randomized controlled trial in the People's Republic of China. Methodology/Principal findings The hookworm CR and fecal ERR were assessed in 314 individuals aged ≥5 years who submitted two stool samples before and 3–4 weeks after administration of single-dose oral albendazole (400 mg) or mebendazole (500 mg) or triple-dose albendazole (3×400 mg over 3 consecutive days) or mebendazole (3×500 mg over 3 consecutive days). Efficacy against T. trichiura, Ascaris lumbricoides, and Taenia spp. was also assessed. Albendazole cured significantly more hookworm infections than mebendazole in both treatment regimens (single dose: respective CRs 69% (95% confidence interval [CI]: 55–81%) and 29% (95% CI: 20–45%); triple dose: respective CRs 92% (95% CI: 81–98%) and 54% (95% CI: 46–71%)). ERRs followed the same pattern (single dose: 97% versus 84%; triple dose: 99.7% versus 96%). Triple-dose regimens outperformed single doses against T. trichiura; three doses of mebendazole – the most efficacious treatment tested – cured 71% (95% CI: 57–82%). Both single and triple doses of either drug were highly efficacious against A. lumbricoides (CR: 93–97%; ERR: all >99.9%). Triple dose regimens cured all Taenia spp. infections, whereas single dose applications cured only half of them. Conclusions/Significance Single-dose oral albendazole is more efficacious against hookworm than mebendazole. To achieve high CRs against both hookworm and T. trichiura, triple-dose regimens are

  13. High-dose nifuratel for simple and mixed aerobic vaginitis: A single-center prospective open-label cohort study.

    Science.gov (United States)

    Liang, Qian; Li, Nan; Song, Shurong; Zhang, Aihua; Li, Ni; Duan, Ying

    2016-10-01

    The efficacy and safety of two nifuratel dosages for the treatment of aerobic vaginitis (AV) were compared. This was a prospective open-label cohort study of patients diagnosed and treated at the Tianjin Third Central Hospital between January 2012 and December 2013. The co-presence of bacterial vaginosis (BV), vulvovaginal candidiasis (VVC), or/and trichomonal vaginitis (TV; mixed AV) was determined. Patients were randomized to nifuratel-500 (500 mg nifuratel, intravaginal, 10 days) or nifuratel-250 (250 mg nifuratel, intravaginal, 10 days), and followed-up for three to seven days after treatment completion. Primary and secondary outcomes were recovery rate and adverse events, respectively. The study included 142 patients with AV. Age was not significantly different between the groups (n = 71 each), and disease distribution was identical: 29 (40.85%) simple AV and 42 (59.15%) mixed AV (AV + BV, 42.86 %; AV + VVC, 30.95%; AV + TV, 26.19%). In patients with simple AV, the recovery rate did not differ significantly between the nifuratel-500 (26/29, 89.66%) and nifuratel-250 (22/29, 75.86%) groups. In patients with mixed AV, recovery rates were significantly higher in the nifuratel-500 than in the nifuratel-250 group (AV + BV, 88.89% vs 50.00 %; AV + VVC, 76.92 % vs 30.77 %; AV + TV, 90.91 % vs 36.36%; all P < 0.05). Only one patient (nifuratel-500) reported an adverse event (mild anaphylactic reaction). Nifuratel 500 mg showed good clinical efficacy for the treatment of AV, particularly mixed AV, and is superior to the 250 mg dosage in the treatment of mixed AV. © 2016 Japan Society of Obstetrics and Gynecology.

  14. A Single-Center, Open-Label, 3-Way Crossover Trial to Determine the Pharmacokinetic and Pharmacodynamic Interaction Between Nebivolol and Valsartan in Healthy Volunteers at Steady State.

    Science.gov (United States)

    Chen, Chun Lin; Desai-Krieger, Daksha; Ortiz, Stephan; Kerolous, Majid; Wright, Harold M; Ghahramani, Parviz

    2015-01-01

    Combining different classes of antihypertensives is more effective for reducing blood pressure (BP) than increasing the dose of monotherapies. The aims of this phase I study were to investigate pharmacokinetic and pharmacodynamic interactions between nebivolol, a vasodilatory β1-selective blocker, and valsartan, an angiotensin II receptor blocker, and to assess safety and tolerability of the combination. This was a single-center, randomized, open-label, multiple-dose, 3-way crossover trial in 30 healthy adults aged 18-45 years. Participants were randomized into 1 of 6 treatment sequences (1:1:1:1:1:1) consisting of three 7-day treatment periods followed by a 7-day washout. Once-daily oral treatments comprised nebivolol (20 mg), valsartan (320 mg), and nebivolol-valsartan combination (20/320 mg). Outcomes included AUC0-τ,ss, Cmax,ss, Tmax,ss, changes in BP, pulse rate, plasma angiotensin II, plasma renin activity, 24-hour urinary aldosterone, and adverse events. Steady-state pharmacokinetic interactions were observed but deemed not clinically significant. Systolic and diastolic BP reduction was significantly greater with nebivolol-valsartan combination than with either monotherapy. The mean pulse rate associated with nebivolol and nebivolol-valsartan treatments was consistently lower than that associated with valsartan monotherapy. A sharp increase in mean day 7 plasma renin activity and plasma angiotensin II that occurred in valsartan-treated participants was significantly attenuated with concomitant nebivolol administration. Mean 24-hour urine aldosterone at day 7 was substantially decreased after combined treatment, as compared with either monotherapy. All treatments were safe and well tolerated. In conclusion, nebivolol and valsartan coadministration led to greater reductions in BP compared with either monotherapy; nebivolol and valsartan lower BP through complementary mechanisms.

  15. Efficacy and safety of amphotericin B emulsion versus liposomal formulation in Indian patients with visceral leishmaniasis: a randomized, open-label study.

    Directory of Open Access Journals (Sweden)

    Shyam Sundar

    2014-09-01

    Full Text Available India is home to 60% of the total global visceral leishmaniasis (VL population. Use of long-term oral (e.g. miltefosine and parenteral drugs, considered the mainstay for treatment of VL, is now faced with increased resistance, decreased efficacy, low compliance and safety issues. The authors evaluated the efficacy and safety of an alternate treatment option, i.e. single infusion of preformed amphotericin B (AmB lipid emulsion (ABLE in comparison with that of liposomal formulation (LAmB.In this multicentric, open-label study, 500 patients with VL were randomly assigned in a 3:1 ratio to receive 15 mg/kg single infusion of either ABLE (N = 376 or LAmB (N = 124. Initial cure (Day 30/45, clinical improvement (Day 30 and long term definitive cure (Day 180 were assessed.A total of 326 (86.7% patients in the ABLE group and 122 (98.4% patients in the LAmB group completed the study. Initial cure was achieved by 95.9% of patients in the ABLE group compared to 100% in the LAmB group (p = 0.028; 95% CI: -0.0663, -0.0150. Clinical improvement was comparable between treatments (ABLE: 98.9% vs. LAmB: 98.4%. Definitive cure was achieved in 85.9% with ABLE compared to 98.4% with LAmB. Infusion-related pyrexia (37.2% vs. 32.3% and chills (18.4% vs. 18.5% were comparable between ABLE and LAmB, respectively. Treatment-related serious adverse events were fewer in ABLE (0.3% compared to LAmB (1.6%. Two deaths occurred in the ABLE group, of which one was probably related to the study drug. Nephrotoxicity and hepatotoxicity was not observed in either group.ABLE 15 mg/kg single infusion had favorable efficacy and was well tolerated. Considering the demographic profile of the population in this region, a single dose treatment offers advantages in terms of compliance, cost and applicability.www.clinicaltrials.gov NCT00876824.

  16. Radiotherapy for calcaneodynia. Results of a single center prospective randomized dose optimization trial

    Energy Technology Data Exchange (ETDEWEB)

    Ott, O.J.; Jeremias, C.; Gaipl, U.S.; Frey, B.; Schmidt, M.; Fietkau, R. [University Hospital Erlangen (Germany). Dept. of Radiation Oncology

    2013-04-15

    The aim of this work was to compare the efficacy of two different dose fractionation schedules for radiotherapy of patients with calcaneodynia. Between February 2006 and April 2010, 457 consecutive evaluable patients were recruited for this prospective randomized trial. All patients received radiotherapy using the orthovoltage technique. One radiotherapy series consisted of 6 single fractions/3 weeks. In case of insufficient remission of pain after 6 weeks a second radiation series was performed. Patients were randomly assigned to receive either single doses of 0.5 or 1.0 Gy. Endpoint was pain reduction. Pain was measured before, immediately after, and 6 weeks after radiotherapy using a visual analogue scale (VAS) and a comprehensive pain score (CPS). The overall response rate for all patients was 87 % directly after and 88 % 6 weeks after radiotherapy. The mean VAS values before, immediately after, and 6 weeks after treatment for the 0.5 and 1.0 Gy groups were 65.5 {+-} 22.1 and 64.0 {+-} 20.5 (p = 0.188), 34.8 {+-} 24.7 and 39.0 {+-} 26.3 (p = 0.122), and 25.1 {+-} 26.8 and 28.9 {+-} 26.8 (p = 0.156), respectively. The mean CPS before, immediately after, and 6 weeks after treatment was 10.1 {+-} 2.7 and 10.0 {+-} 3.0 (p = 0.783), 5.6 {+-} 3.7 and 6.0 {+-} 3.9 (p = 0.336), 4.0 {+-} 4.1 and 4.3 {+-} 3.6 (p = 0.257), respectively. No statistically significant differences between the two single dose trial arms for early (p = 0.216) and delayed response (p = 0.080) were found. Radiotherapy is an effective treatment option for the management of calcaneodynia. For radiation protection reasons, the dose for a radiotherapy series is recommended not to exceed 3-6 Gy. (orig.)

  17. Bioequivalence of two film-coated tablets of imatinib mesylate 400 mg: a randomized, open-label, single-dose, fasting, two-period, two-sequence crossover comparison in healthy male South American volunteers.

    Science.gov (United States)

    Parrillo-Campiglia, Susana; Ercoli, Mónica Cedres; Umpierrez, Ofelia; Rodríguez, Patricia; Márquez, Sara; Guarneri, Carolina; Estevez-Parrillo, Francisco T; Laurenz, Marilena; Estevez-Carrizo, Francisco E

    2009-10-01

    Imatinib is a tyrosine kinase inhibitor that has been established as a highly effective therapy for chronic myelogenous leukemia and gastrointestinal stromal tumors. A new generic, once-daily 400-mg tablet of imatinib has been developed by a pharmaceutical company in Argentina, where the regulatory standard for marketing authorization of an imatinib generic is in vitro dissolution testing. The aim of this study was to assess the bioequivalence of a new generic film-coated test tablet formulation versus a film-coated reference tablet formulation of imatinib 400 mg. The local manufacturer seeks to validate the in vitro performance of this new formulation with a bioequivalence study. A randomized, open-label, single-dose, fasting, 2-period, 2-sequence crossover design with a 2-week washout period was used in this study. The study population consisted of healthy male South American (Uruguayan) volunteers, who were assigned in a 1:1 ratio to a randomized sequence (test-reference or reference-test). In each period, the test or reference formulation was administered after an overnight fast. During the 72-hour follow-up period, participants were monitored for vital signs and symptoms. Blood samples were collected at 15 time points, including baseline, until 72 hours. Physical examination and laboratory tests (blood, urine) were repeated 1 week after study completion. A noncompartmental model was used to determine the pharmacokinetic parameters of imatinib. The 90% CIs of the test/reference ratios for AUC(0-infinity) and C(max) were determined; the test and reference formulations were considered bioequivalent if the 90% CIs were between 0.80 and 1.25. Adverse events were assessed by a nurse who administered a questionnaire while the healthy volunteers were admitted in the unit. The bioequivalence study was conducted in 30 Uruguayan male volunteers. Demographic characteristics (mean [SD]) included age, 27.8 (6.5) years; weight, 71.2 (9.8) kg; height, 1.71 (0.09) m; and body

  18. Pharmacokinetics of pregabalin controlled-release in healthy volunteers: effect of food in five single-dose, randomized, clinical pharmacology studies.

    Science.gov (United States)

    Chew, Marci L; Plotka, Anna; Alvey, Christine W; Pitman, Verne W; Alebic-Kolbah, Tanja; Scavone, Joseph M; Bockbrader, Howard N

    2014-09-01

    The pharmacokinetic properties of the immediate-release (IR) and the recently developed controlled-release (CR) formulation of pregabalin are dose proportional. Pregabalin IR can be taken with or without food. This analysis characterizes the effect of food on pregabalin CR. The objectives of this analysis were: (1) to evaluate the effect of administration time and fat or caloric content of an accompanying meal on the pharmacokinetic properties of a single dose of pregabalin CR (330 mg) relative to a single dose of pregabalin IR (300 mg); (2) to evaluate the pharmacokinetic properties of a single dose of pregabalin CR administered fasted relative to a single dose of pregabalin CR administered immediately after food; and (3) to determine the safety and tolerability of single-dose administration of pregabalin CR and IR with and without food. The effect of food on the pharmacokinetic properties of pregabalin CR was determined in five phase I, open-label, single-dose, crossover studies (24-28 participants/study). Caloric and fat content of meals were varied and treatments were administered in the morning, at midday, or in the evening. Blood samples were collected up to 48 h post-dose. Pharmacokinetic parameters were estimated from plasma concentration-time data using standard noncompartmental methods. Adverse events were monitored throughout all studies. One hundred and twenty-eight healthy participants (19-54 years of age) received pregabalin. Peak plasma concentrations (C max) were lower for CR than the respective pregabalin IR doses, and time to C max occurred later. When pregabalin CR was administered with food at midday or in the evening, total exposures [area under the plasma concentration-time curve from time zero extrapolated to infinite time (AUC∞)] were equivalent for pregabalin CR and IR formulations regardless of fat or caloric content. When pregabalin CR was administered with an 800-1,000 calorie medium-fat breakfast, AUC∞ was equivalent for

  19. Open-Label, Randomized Study of Transition From Tacrolimus to Sirolimus Immunosuppression in Renal Allograft Recipients

    Science.gov (United States)

    Tedesco-Silva, Helio; Peddi, V. Ram; Sánchez-Fructuoso, Ana; Marder, Brad A.; Russ, Graeme R.; Diekmann, Fritz; Flynn, Alison; Hahn, Carolyn M.; Li, Huihua; Tortorici, Michael A.; Schulman, Seth L.

    2016-01-01

    Background Calcineurin inhibitor–associated nephrotoxicity and other adverse events have prompted efforts to minimize/eliminate calcineurin inhibitor use in kidney transplant recipients. Methods This open-label, randomized, multinational study evaluated the effect of planned transition from tacrolimus to sirolimus on kidney function in renal allograft recipients. Patients received tacrolimus-based immunosuppression and then were randomized 3 to 5 months posttransplantation to transition to sirolimus or continue tacrolimus. The primary end point was percentage of patients with 5 mL/min per 1.73 m2 or greater improvement in estimated glomerular filtration rate from randomization to month 24. Results The on-therapy population included 195 patients (sirolimus, 86; tacrolimus, 109). No between-group difference was noted in percentage of patients with 5 mL/min per 1.73 m2 or greater estimated glomerular filtration rate improvement (sirolimus, 34%; tacrolimus, 42%; P = 0.239) at month 24. Sirolimus patients had higher rates of biopsy-confirmed acute rejection (8% vs 2%; P = 0.02), treatment discontinuation attributed to adverse events (21% vs 3%; P renal function improvement at 24 months is similar for patients with early conversion to sirolimus after kidney transplantation versus those remaining on tacrolimus. PMID:27500260

  20. Single- and multiple-dose pharmacokinetics and absolute bioavailability of tedizolid.

    Science.gov (United States)

    Flanagan, Shawn; Fang, Edward; Muñoz, Kelly A; Minassian, Sonia L; Prokocimer, Philippe G

    2014-09-01

    Tedizolid phosphate is a novel antibacterial under investigation for the treatment of gram-positive infections. This study was conducted to assess the pharmacokinetics, safety, and tolerability of intravenous tedizolid phosphate as well as the oral bioavailability of tedizolid phosphate. Double-blind, single-ascending dose, multiple-dose pharmacokinetics study, as well as tolerability and open-label crossover studies. Single center in the United States (Covance Clinical Research Unit, Madison, WI) between September 2009 and January 2010. Ninety healthy volunteers. Single intravenous (IV) doses of tedizolid phosphate 50 mg (lead-in) and 100-400 mg. Single oral and IV dose of tedizolid phosphate 200 mg in crossover fashion. Multiple IV doses of tedizolid phosphate 200 and 300 mg for up to 7 days. A dose-dependent increase was observed in the maximum plasma concentration (1.2-5.1 μg/ml) and the area under the concentration-time curve (17.4-58.7 μg × hr/ml) of tedizolid (the microbiologically active moiety of tedizolid phosphate) after single IV doses of tedizolid phosphate 100-400 mg. Administration of IV tedizolid phosphate 200 mg once/day for 7 days resulted in minimal (28%) tedizolid accumulation. The absolute oral bioavailability of tedizolid after a single 200-mg dose of tedizolid phosphate was 91%; pharmacokinetic parameters of tedizolid were similar with oral and IV administration. Treatment-related adverse events occurred in 41% of subjects. Most adverse events were related to infusion site and became more frequent with multiple dosing. In an additional 3-day tolerability study, IV tedizolid phosphate 200 mg and placebo were similarly tolerated, based on visual infusion phlebitis scores. These results from a population of healthy volunteers support once/day dosing of tedizolid phosphate 200 mg with both the oral and IV formulations, without the need for dose adjustment when switching administration routes. © 2014 Cubist Pharmaceuticals. Pharmacotherapy

  1. Microbial contamination and labelling of self-prepared, multi-dose ...

    African Journals Online (AJOL)

    Labelling data were written directly on 100% of the containers and a spike- device was ... are associated with the use of single-dose vials for multiple patients18–20 .... medication should sign the medication container.25,49 In our study only ...

  2. Evaluation of two novel tablet formulations of artemether-lumefantrine (Coartem) for bioequivalence in a randomized, open-label, two-period study.

    Science.gov (United States)

    Lefèvre, Gilbert; Bhad, Prafulla; Jain, Jay Prakash; Kalluri, Sampath; Cheng, Yi; Dave, Hardik; Stein, Daniel S

    2013-09-08

    Artemether-lumefantrine (Coartem; AL) is a standard of care for malaria treatment as an oral six-dose regimen, given twice daily over three days with one to four tablets (20/120 mg) per dose, depending on patient body weight. In order to reduce the pill burden at each dose and potentially enhance compliance, two novel fixed-dose tablet formulations (80/480 mg and 60/360 mg) have been developed and tested in this study for bioequivalence with their respective number of standard tablets. A randomized, open-label, two-period, single-dose, within formulation crossover bioequivalence study comparing artemether and lumefantrine exposure between the novel 80/480 mg tablet and four standard tablets, and the novel 60/360 mg tablet and three standard tablets, was conducted in 120 healthy subjects under fed conditions. Artemether, dihydroartemisinin, and lumefantrine were measured in plasma by HPLC/UPLC-MS/MS. Pharmacokinetic (PK) parameters were determined by non-compartmental analyses. Adjusted geometric mean AUClast for artemether were 345 and 364 ng·h/mL (geometric mean ratio (GMR) 0.95; 90% CI 0.89-1.01) and for lumefantrine were 219 and 218 μg·h/mL (GMR 1.00; 90% CI 0.93-1.08) for 80/480 mg tablet versus four standard tablets, respectively. Corresponding Cmax for artemether were 96.8 and 99.7 ng/mL (GMR 0.97; 90% CI 0.89-1.06) and for lumefantrine were 8.42 and 8.71 μg/mL (GMR 0.97; 90% CI 0.89-1.05). For the 60/360 mg tablet versus three standard tablets, adjusted geometric mean AUClast for artemether were 235 and 231 ng·h/mL (GMR 1.02; 90% CI 0.94-1.10), and for lumefantrine were 160 and 180 μg·h/mL (GMR 0.89; 90% CI 0.83-0.96), respectively. Corresponding Cmax for artemether were 75.5 and 71.5 ng/mL (GMR 1.06; 90% CI 0.95-1.18), and for lumefantrine were 6.64 and 7.61 μg/mL (GMR 0.87; 90% CI 0.81-0.94), respectively. GMR for Cmax and AUClast for artemether and lumefantrine for all primary comparisons were within the bioequivalence acceptance criteria (0

  3. Single therapeutic and supratherapeutic doses of sacubitril/valsartan (LCZ696) do not affect cardiac repolarization.

    Science.gov (United States)

    Langenickel, Thomas H; Jordaan, Pierre; Petruck, Jesika; Kode, Kiran; Pal, Parasar; Vaidya, Soniya; Chandra, Priya; Rajman, Iris

    2016-08-01

    Sacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor (ARNI) indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA class II-IV) and reduced ejection fraction. This study was aimed to evaluate the effect of single oral therapeutic (400 mg) and supratherapeutic (1200 mg) doses of LCZ696 on cardiac repolarization. This randomized double-blind crossover study in healthy male subjects compared the effect of therapeutic and supratherapeutic doses of LCZ696 with placebo and moxifloxacin 400 mg (open-label treatment) as positive control. The primary assessment was mean baseline- and placebo-corrected QTcF (∆∆QTcF; Fridericia correction). Additional assessments included the ∆∆QTcB (Bazett's correction), PR interval, QRS duration, heart rate (HR), LCZ696 pharmacokinetics, pharmacokinetic/pharmacodynamic relationships, and safety. Of the 84 subjects enrolled, 81 completed the study. The maximum upper bound of the two-sided 90 % confidence interval for ∆∆QTcF for LCZ696 400 mg and 1200 mg were <10 ms, and assay sensitivity was confirmed with moxifloxacin. No relevant treatment-emergent changes were observed in any of the ECG-derived parameters with LCZ696 or placebo, and the incidence of adverse events was comparable among the treatment groups. Single therapeutic and supratherapeutic doses of LCZ696 did not affect cardiac repolarization as defined by the E14 ICH guidelines.

  4. Open-label, randomized study of individualized, pharmacokinetically (PK)-guided dosing of paclitaxel combined with carboplatin or cisplatin in patients with advanced non-small-cell lung cancer (NSCLC).

    Science.gov (United States)

    Joerger, M; von Pawel, J; Kraff, S; Fischer, J R; Eberhardt, W; Gauler, T C; Mueller, L; Reinmuth, N; Reck, M; Kimmich, M; Mayer, F; Kopp, H-G; Behringer, D M; Ko, Y-D; Hilger, R A; Roessler, M; Kloft, C; Henrich, A; Moritz, B; Miller, M C; Salamone, S J; Jaehde, U

    2016-10-01

    Variable chemotherapy exposure may cause toxicity or lack of efficacy. This study was initiated to validate pharmacokinetically (PK)-guided paclitaxel dosing in patients with advanced non-small-cell lung cancer (NSCLC) to avoid supra- or subtherapeutic exposure. Patients with newly diagnosed, advanced NSCLC were randomly assigned to receive up to 6 cycles of 3-weekly carboplatin AUC 6 or cisplatin 80 mg/m(2) either with standard paclitaxel at 200 mg/m(2) (arm A) or PK-guided dosing of paclitaxel (arm B). In arm B, initial paclitaxel dose was adjusted to body surface area, age, sex, and subsequent doses were guided by neutropenia and previous-cycle paclitaxel exposure [time above a plasma concentration of 0.05 µM (Tc>0.05)] determined from a single blood sample on day 2. The primary end point was grade 4 neutropenia; secondary end points included neuropathy, radiological response, progression-free survival (PFS) and overall survival (OS). Among 365 patients randomly assigned, grade 4 neutropenia was similar in both arms (19% versus 16%; P = 0.10). Neuropathy grade ≥2 (38% versus 23%, P PK-guided dosing of paclitaxel does not improve severe neutropenia, but reduces paclitaxel-associated neuropathy and thereby improves the benefit-risk profile in patients with advanced NSCLC. NCT01326767 (https://clinicaltrials.gov/ct2/show/NCT01326767). © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  5. The effect of increasing the dose of hydroxychloroquine (HCQ) in patients with refractory cutaneous lupus erythematosus (CLE): An open-label prospective pilot study.

    Science.gov (United States)

    Chasset, François; Arnaud, Laurent; Costedoat-Chalumeau, Nathalie; Zahr, Noel; Bessis, Didier; Francès, Camille

    2016-04-01

    Up to 30% of patients with cutaneous lupus erythematosus (CLE) fail to respond to hydroxychloroquine (HCQ). We sought to evaluate the efficacy of increased daily doses of HCQ on cutaneous response in refractory CLE. We conducted an open-label prospective study between 2010 and 2014. Patients with CLE and HCQ blood level less than or equal to 750 ng/mL were included. The daily dose of HCQ was increased to reach blood concentrations greater than 750 ng/mL. The primary end point was the number of responders defined by an improvement of CLE Disease Area and Severity Index score (4 points or 20% decrease) in patients with HCQ blood concentration greater than 750 ng/mL. We included 34 patients (26 women; median age 45 [range 28-72] years). Two nonadherent patients were excluded. The median CLE Disease Area and Severity Index score before treatment was significantly improved after treatment (8 [range 2-30] vs 1.5 [range 0-30]), P < .001). The primary response criterion was reached in 26 (81%) of the 32 patients analyzed. A decrease in HCQ doses without further CLE flare (median follow-up 15.8 [range 3.06-77.4] months) was achieved in 15 of the 26 responders. The main limitations of the study are its open-label design and the limited number of patients included. Increasing HCQ doses to reach blood concentrations greater than 750 ng/mL should be considered before addition of other treatments in refractory CLE. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  6. Comparison of Low-Dose Rosuvastatin with Atorvastatin in Lipid-Lowering Efficacy and Safety in a High-Risk Pakistani Cohort: An Open-Label Randomized Trial

    Directory of Open Access Journals (Sweden)

    Abdul Rehman Arshad

    2014-01-01

    Full Text Available Background. Treatment of hyperlipidemia is helpful in both primary and secondary prevention of coronary heart disease and stroke. Aim. To compare lipid-lowering efficacy of rosuvastatin with atorvastatin. Methodology. This open-label randomized controlled trial was carried out at 1 Mountain Medical Battalion from September 2012 to August 2013 on patients with type 2 diabetes, hypertension, myocardial infarction, or stroke, meriting treatment with a statin. Those with secondary causes of dyslipidemia were excluded. Blood samples for estimation of serum total cholesterol, triglycerides, HDL-C, and LDL-C were collected after a 12-hour fast. Patients were randomly allocated to receive either atorvastatin 10 mg HS or rosuvastatin 5 mg HS daily. Lipid levels were rechecked after six weeks. Results. Atorvastatin was used in 63 patients and rosuvastatin in 66. There was a greater absolute and percent reduction in serum LDL-C levels with rosuvastatin as compared to atorvastatin (0.96 versus 0.54 mg/dL; P=0.011 and 24.34 versus 13.66%; P=0.045, whereas reduction in all other fractions was equal. Myalgias were seen in 5 (7.94% patients treated with atorvastatin and 8 (12.12% patients treated with rosuvastatin (P: 0.432. Conclusion. Rosuvastatin produces a greater reduction in serum LDL-C levels and should therefore be preferred over atorvastatin.

  7. Evaluation of dose reduction versus standard dosing for maintenance of remission in patients with spondyloarthritis and clinical remission with anti-TNF (REDES-TNF): study protocol for a randomized controlled trial.

    Science.gov (United States)

    Pontes, Caridad; Gratacós, Jordi; Torres, Ferran; Avendaño, Cristina; Sanz, Jesús; Vallano, Antoni; Juanola, Xavier; de Miguel, Eugenio; Sanmartí, Raimon; Calvo, Gonzalo

    2015-08-20

    Dose reduction schedules of tumor necrosis factor antagonists (anti-TNF) as maintenance therapy in patients with spondyloarthritis are used empirically in clinical practice, despite the lack of clinical trials providing evidence for this practice. To address this issue the Spanish Society of Rheumatology (SER) and Spanish Society of Clinical Pharmacology (SEFC) designed a 3-year multicenter, randomized, open-label, controlled clinical trial (2 years for inclusion and 1 year of follow-up). The study is expected to include 190 patients with axial spondyloarthritis on stable maintenance treatment (≥4 months) with any anti-TNF agent at doses recommended in the summary of product characteristics. Patients will be randomized to either a dose reduction arm or maintenance of the dosing regimen as per the official labelling recommendations. Randomization will be stratified according to the anti-TNF agent received before study inclusion. Patient follow-up, visit schedule, and examinations will be maintained as per normal clinical practice recommendations according to SER guidelines. The study aims to test the hypothesis of noninferiority of the dose reduction strategy compared with standard treatment. The first patients were recruited in July 2012, and study completion is scheduled for the end of April 2015. The REDES-TNF study is a pragmatic clinical trial that aims to provide evidence to support a medical decision now made empirically. The study results may help inform clinical decisions relevant to both patients and healthcare decision makers. EudraCT 2011-005871-18 (21 December 2011).

  8. Oral versus intramuscular cobalamin treatment in megaloblastic anemia: a single-center, prospective, randomized, open-label study.

    Science.gov (United States)

    Bolaman, Zahit; Kadikoylu, Gurhan; Yukselen, Vahit; Yavasoglu, Irfan; Barutca, Sabri; Senturk, Taskin

    2003-12-01

    Cobalamin (vitamin B12) deficiency, the most common cause of megaloblastic anemia, is treated with intramuscular (IM) cobalamin. It has been suggested by some investigators that oral (p.o.) cobalamin treatment may be as effective in the treatment of this condition, with the advantages of ease of administration and lower cost. This study assessed the effects and cost of p.o. versus i.m. cobalamin treatment in patients with megaloblastic anemia due to cobalamin deficiency. This was a 90-day, prospective, randomized, open-label study conducted at the Division of Hematology, Department of Internal Medicine, Adnan Menderes University Research and Practice Hospital (Aydin, Turkey). Patients aged > or =16 years with megaloblastic anemia due to cobalamin deficiency were randomized to receive 1000-microg cobalamin p.o. once daily for 10 days (p.o. group) or 1000-microg cobalamin i.m. once daily for 10 days (i.m. group). After 10 days, both treatments were administered once a week for 4 weeks, and after that, once a month for life. Patients were assessed for the presence of reticulocytosis between treatment days 5 and 10 until it was detected. Therapeutic effectiveness was assessed by measuring hematologic parameters on days 0, 10, 30, and 90 and serum vitamin B12 concentration on days 0 and 90. The Mini-Mental State Examination was used before and after the B12 therapy for cognitive function assessment and 125-Hz diapozone was used for vibration threshold testing. Neurologic sensory assessment, including soft-touch and pinprick examinations, was used to identify neuropathy at baseline and study end. Tolerability was assessed using laboratory tests and patient interview. Cost was assessed using the cost of the study drug and of the injection. Sixty patients completed the study 26 in the p.o. group (16 men, 10 women; mean [SD] age, 60 [15] years) and 34 in the i.m. group (17 men, 17 women; mean [SD] age, 64 [10] years). Reticulocytosis was observed in all patients. In the p

  9. Safety and Efficacy of Memantine in Children with Autism: Randomized, Placebo-Controlled Study and Open-Label Extension.

    Science.gov (United States)

    Aman, Michael G; Findling, Robert L; Hardan, Antonio Y; Hendren, Robert L; Melmed, Raun D; Kehinde-Nelson, Ola; Hsu, Hai-An; Trugman, Joel M; Palmer, Robert H; Graham, Stephen M; Gage, Allyson T; Perhach, James L; Katz, Ephraim

    2017-06-01

    Abnormal glutamatergic neurotransmission is implicated in the pathophysiology of autism spectrum disorder (ASD). In this study, the safety, tolerability, and efficacy of the glutamatergic N-methyl-d-aspartate (NMDA) receptor antagonist memantine (once-daily extended-release [ER]) were investigated in children with autism in a randomized, placebo-controlled, 12 week trial and a 48 week open-label extension. A total of 121 children 6-12 years of age with Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR)-defined autistic disorder were randomized (1:1) to placebo or memantine ER for 12 weeks; 104 children entered the subsequent extension trial. Maximum memantine doses were determined by body weight and ranged from 3 to 15 mg/day. There was one serious adverse event (SAE) (affective disorder, with memantine) in the 12 week study and one SAE (lobar pneumonia) in the 48 week extension; both were deemed unrelated to treatment. Other AEs were considered mild or moderate and most were deemed not related to treatment. No clinically significant changes occurred in clinical laboratory values, vital signs, or electrocardiogram (ECG). There was no significant between-group difference on the primary efficacy outcome of caregiver/parent ratings on the Social Responsiveness Scale (SRS), although an improvement over baseline at Week 12 was observed in both groups. A trend for improvement at the end of the 48 week extension was observed. No improvements in the active group were observed on any of the secondary end-points, with one communication measure showing significant worsening with memantine compared with placebo (p = 0.02) after 12 weeks. This trial did not demonstrate clinical efficacy of memantine ER in autism; however, the tolerability and safety data were reassuring. Our results could inform future trial design in this population and may facilitate the investigation of memantine ER for other clinical applications.

  10. Armodafinil for fatigue associated with menopause: an open-label trial.

    Science.gov (United States)

    Meyer, Fremonta; Freeman, Marlene P; Petrillo, Laura; Barsky, Maria; Galvan, Thania; Kim, Semmie; Cohen, Lee; Joffe, Hadine

    2016-02-01

    This study aims to obtain preliminary data on the efficacy of armodafinil for improving menopause-related fatigue and quality of life. Women (aged 40-65 y) experiencing menopause-related fatigue received open-label armodafinil therapy (up to 150 mg/d) for 4 weeks. Changes from baseline in Brief Fatigue Inventory score and Menopause-Specific Quality of Life (MENQOL) physical domain score were examined using the Wilcoxon signed rank test. Exploratory analyses examined the effects of armodafinil on hot flashes, overall quality of life, insomnia, depression, anxiety, and perceived cognitive performance. After open-label treatment, participants were randomized to double-blind continuation of armodafinil versus placebo for 2 weeks to examine whether treatment discontinuation would precipitate symptom recurrence. Of 29 eligible participants, 20 women (69.0%) completed the trial. During treatment with armodafinil (mean dose, 120 mg/d), median Brief Fatigue Inventory scores decreased by 57.7% from 5.2 (interquartile range [IQR], 4.6-6.2) to 2.2 (IQR, 1.1-4.4; P = 0.0002), and median MENQOL physical domain scores decreased by 51.3% from 3.9 (IQR, 2.3-4.8) to 1.9 (IQR, 1.3-2.7; P = 0.0001). Median hot flashes for 24 hours decreased by 48.3% from 2.9 (IQR, 1.1-4.6) to 1.5 (IQR, 0.4-2.4; P = 0.0005). Improvements in MENQOL total score (49%; P = 0.0001), cognitive function (59.2%; P = 0.0002), depressive symptoms (64.7%; P = 0.0006), insomnia (72.7%; P = 0.0012), and excessive sleepiness (57.1%; P = 0.0006) were noted. Randomized continuation (n = 10) or discontinuation (n = 10) did not indicate group differences. Armodafinil was well-tolerated; three women (12%) were withdrawn for adverse events. These preliminary results suggest a therapeutic effect of armodafinil on fatigue affecting quality of life during menopause, and a potential benefit for other menopause-related symptoms.

  11. Radiation dose estimates for carbon-11-labelled PET tracers

    International Nuclear Information System (INIS)

    Aart, Jasper van der; Hallett, William A.; Rabiner, Eugenii A.; Passchier, Jan; Comley, Robert A.

    2012-01-01

    Introduction: Carbon-11-labelled positron emission tomography (PET) tracers commonly used in biomedical research expose subjects to ionising radiation. Dosimetry is the measurement of radiation dose, but also commonly refers to the estimation of health risk associated with ionising radiation. This review describes radiation dosimetry of carbon-11-labelled molecules in the context of current PET research and the most widely used regulatory guidelines. Methods: A MEDLINE literature search returned 42 articles; 32 of these were based on human PET data dealing with radiation dosimetry of carbon-11 molecules. Radiation burden expressed as effective dose and maximum absorbed organ dose was compared between tracers. Results: All but one of the carbon-11-labelled PET tracers have an effective dose under 9 μSv/MBq, with a mean of 5.9 μSv/MBq. Data show that serial PET scans in a single subject are feasible for the majority of radiotracers. Conclusion: Although differing in approach, the two most widely used regulatory frameworks (those in the USA and the EU) do not differ substantially with regard to the maximum allowable injected activity per PET study. The predictive validity of animal dosimetry models is critically discussed in relation to human dosimetry. Finally, empirical PET data are related to human dose estimates based on homogenous distribution, generic models and maximum cumulated activities. Despite the contribution of these models to general risk estimation, human dosimetry studies are recommended where continued use of a new PET tracer is foreseen.

  12. Bioequivalence of generic alendronate sodium tablets (70 mg to Fosamax® tablets (70 mg in fasting, healthy volunteers: a randomized, open-label, three-way, reference-replicated crossover study

    Directory of Open Access Journals (Sweden)

    Zhang Y

    2017-07-01

    Full Text Available Yifan Zhang,1 Xiaoyan Chen,1 Yunbiao Tang,2 Youming Lu,1 Lixia Guo,1 Dafang Zhong1 1State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 2Department of Pharmacy, The General Hospital of Shenyang Military Region, Shenyang, People’s Republic of China Purpose: The aim of this study was to evaluate the bioequivalence of a generic product 70 mg alendronate sodium tablets with the reference product Fosamax® 70 mg tablet. Materials and methods: A single-center, open-label, randomized, three-period, three-sequence, reference-replicated crossover study was performed in 36 healthy Chinese male volunteers under fasting conditions. In each study period, the volunteers received a single oral dose of the generic or reference product (70 mg. Blood samples were collected at pre-dose and up to 8 h after administration. The bioequivalence of the generic product to the reference product was assessed using the US Food and Drug Administration (FDA and European Medicines Agency (EMA reference-scaled average bioequivalence (RSABE methods. Results: The average maximum concentrations (Cmax of alendronic acid were 64.78±43.76, 56.62±31.95, and 60.15±37.12 ng/mL after the single dose of the generic product and the first and second doses of the reference product, respectively. The areas under the plasma concentration–time curves from time 0 to the last timepoint (AUC0–t were 150.36±82.90, 148.15±85.97, and 167.11±110.87 h·ng/mL, respectively. Reference scaling was used because the within-subject standard deviations of the reference product (sWR for Cmax and AUC0–t were all higher than the cutoff value of 0.294. The 95% upper confidence bounds were -0.16 and -0.17 for Cmax and AUC0–t, respectively, and the point estimates for the generic/reference product ratio were 1.08 and 1.00, which satisfied the RSABE acceptance criteria of the FDA. The 90% CIs for Cmax and AUC0–t were 90.35%–129

  13. An Open-Label, Multicenter, Randomized, Phase II Study of Pazopanib in Combination with Pemetrexed in First-Line Treatment of Patients with Advanced-Stage Non-Small-Cell Lung Cancer

    DEFF Research Database (Denmark)

    Scagliotti, Giorgio V; Felip, Enriqueta; Besse, Benjamin

    2013-01-01

    This randomized open-label phase II study evaluated the efficacy, safety, and tolerability of pazopanib in combination with pemetrexed compared with the standard cisplatin/pemetrexed doublet in patients with previously untreated, advanced, nonsquamous non-small-cell lung cancer....

  14. Pharmacokinetic Properties of Three Forms of Vaginal Progesterone Administered in Either Single Or Multiple Dose Regimen in Healthy Post-menopausal Chinese Women

    Directory of Open Access Journals (Sweden)

    Jianzhong Shentu

    2017-04-01

    Full Text Available Objective: A generic vaginal progesterone gel has recently been developed in China. Little is known about its pharmacokinetic properties in Chinese subjects. The purpose of our study was to investigate the pharmacokinetics of three forms of vaginal progesterone gel (test formulations at 4 and 8% strength vs. a reference formulation: Crinone 8% in Chinese healthy post-menopausal women.Methods: This study consisted of two parts study. The part 1 study was a single-center, open-label, 3-period study. Twelve healthy post-menopausal women were to evaluate the safety and pharmacokinetics of 45 mg vaginal progesterone gel (Test 4% following single dose and multiple doses administered once every other day (q.o.d. for six times or once daily (q.d. for 6 days. The part 2 study was a randomized, open-label, 3-stage crossover study. Twelve post-menopausal women received 90 mg vaginal progesterone gel (Test 8% or 90 mg Crinone (Reference 8% following single dose and multiple doses (q.o.d. or q.d.. Plasma concentrations of progesterone were measured up to 72 h by using a validated liquid chromatography tandem-mass spectrometry method. The primary pharmacokinetic parameters, maximum plasma concentration (Cmax and area under the plasma concentration–time curve (AUC from time zero to last measurable concentration (AUC0-t and extrapolated to infinity (AUC0-∞ were compared by an analysis of variance using log-transformed data.Results: Totally 24 subjects were enrolled in and completed the study. Following single dose, The geometric mean Cmax values for Test 4%, Test 8%, and Crinone 8% were 6.35, 10.34, 10.45 ng/mL, and their geometric mean AUC0-t (AUC0-∞ were 113.73 (118.00, 169.39 (173.98, and 190.07 (201.13 ng⋅h/mL, respectively. The mean T1/2 values of progesterone were 11.00, 10.92, and 11.40 h, respectively. For 8% test formulation vs. reference, the 90% CIs of the least squares mean test/reference ratios of Cmax, AUC0-t, and AUC0-∞ were 78.32–124

  15. Effects of switching from olanzapine to aripiprazole on the metabolic profiles of patients with schizophrenia and metabolic syndrome: a double-blind, randomized, open-label study [Corrigendum

    Directory of Open Access Journals (Sweden)

    Wani RA

    2015-03-01

    Full Text Available Wani RA, Dar MA, Chandel RK, et al Title of paper should have been “Effects of switching from olanzapine to aripiprazole on the metabolic profiles of patients with schizophrenia and metabolic syndrome: a randomized, open-label study”.  Read the original paper 

  16. Low efficacy of single-dose albendazole and mebendazole against hookworm and effect on concomitant helminth infection in Lao PDR.

    Directory of Open Access Journals (Sweden)

    Phonepasong Ayé Soukhathammavong

    2012-01-01

    Full Text Available BACKGROUND: Albendazole and mebendazole are increasingly deployed for preventive chemotherapy targeting soil-transmitted helminth (STH infections. We assessed the efficacy of single oral doses of albendazole (400 mg and mebendazole (500 mg for the treatment of hookworm infection in school-aged children in Lao PDR. Since Opisthorchis viverrini is co-endemic in our study setting, the effect of the two drugs could also be determined against this liver fluke. METHODOLOGY: We conducted a randomized, open-label, two-arm trial. In total, 200 children infected with hookworm (determined by quadruplicate Kato-Katz thick smears derived from two stool samples were randomly assigned to albendazole (n=100 and mebendazole (n=100. Cure rate (CR; percentage of children who became egg-negative after treatment, and egg reduction rate (ERR; reduction in the geometric mean fecal egg count at treatment follow-up compared to baseline at 21-23 days posttreatment were used as primary outcome measures. Adverse events were monitored 3 hours post treatment. PRINCIPAL FINDINGS: Single-dose albendazole and mebendazole resulted in CRs of 36.0% and 17.6% (odds ratio: 0.4; 95% confidence interval: 0.2-0.8; P=0.01, and ERRs of 86.7% and 76.3%, respectively. In children co-infected with O. viverrini, albendazole and mebendazole showed low CRs (33.3% and 24.2%, respectively and moderate ERRs (82.1% and 78.2%, respectively. CONCLUSIONS/SIGNIFICANCE: Both albendazole and mebendazole showed disappointing CRs against hookworm, but albendazole cured infection and reduced intensity of infection with a higher efficacy than mebendazole. Single-dose administrations showed an effect against O. viverrini, and hence it will be interesting to monitor potential ancillary benefits of a preventive chemotherapy strategy that targets STHs in areas where opisthorchiasis is co-endemic. CLINICAL TRIAL REGISTRATION: Current Controlled Trials ISRCTN29126001.

  17. Low Efficacy of Single-Dose Albendazole and Mebendazole against Hookworm and Effect on Concomitant Helminth Infection in Lao PDR

    Science.gov (United States)

    Soukhathammavong, Phonepasong Ayé; Sayasone, Somphou; Phongluxa, Khampheng; Xayaseng, Vilavanh; Utzinger, Jürg; Vounatsou, Penelope; Hatz, Christoph; Akkhavong, Kongsap; Keiser, Jennifer; Odermatt, Peter

    2012-01-01

    Background Albendazole and mebendazole are increasingly deployed for preventive chemotherapy targeting soil-transmitted helminth (STH) infections. We assessed the efficacy of single oral doses of albendazole (400 mg) and mebendazole (500 mg) for the treatment of hookworm infection in school-aged children in Lao PDR. Since Opisthorchis viverrini is co-endemic in our study setting, the effect of the two drugs could also be determined against this liver fluke. Methodology We conducted a randomized, open-label, two-arm trial. In total, 200 children infected with hookworm (determined by quadruplicate Kato-Katz thick smears derived from two stool samples) were randomly assigned to albendazole (n = 100) and mebendazole (n = 100). Cure rate (CR; percentage of children who became egg-negative after treatment), and egg reduction rate (ERR; reduction in the geometric mean fecal egg count at treatment follow-up compared to baseline) at 21–23 days posttreatment were used as primary outcome measures. Adverse events were monitored 3 hours post treatment. Principal Findings Single-dose albendazole and mebendazole resulted in CRs of 36.0% and 17.6% (odds ratio: 0.4; 95% confidence interval: 0.2–0.8; P = 0.01), and ERRs of 86.7% and 76.3%, respectively. In children co-infected with O. viverrini, albendazole and mebendazole showed low CRs (33.3% and 24.2%, respectively) and moderate ERRs (82.1% and 78.2%, respectively). Conclusions/Significance Both albendazole and mebendazole showed disappointing CRs against hookworm, but albendazole cured infection and reduced intensity of infection with a higher efficacy than mebendazole. Single-dose administrations showed an effect against O. viverrini, and hence it will be interesting to monitor potential ancillary benefits of a preventive chemotherapy strategy that targets STHs in areas where opisthorchiasis is co-endemic. Clinical Trial Registration Current Controlled Trials ISRCTN29126001 PMID:22235353

  18. Immunogenicity, reactogenicity and safety of 2 doses of an adjuvanted herpes zoster subunit vaccine administered 2, 6 or 12 months apart in older adults: Results of a phase III, randomized, open-label, multicenter study.

    Science.gov (United States)

    Lal, Himal; Poder, Airi; Campora, Laura; Geeraerts, Brecht; Oostvogels, Lidia; Vanden Abeele, Carline; Heineman, Thomas C

    2018-01-02

    In phase III trials, 2 doses of a herpes zoster (HZ) subunit vaccine (HZ/su; 50 µg varicella-zoster virus glycoprotein E [gE] and AS01 B Adjuvant System) administered 2-months apart in older adults (≥50 and ≥70 years) demonstrated >90% efficacy in preventing HZ and had a clinically acceptable safety profile. Here we report immunogenicity, reactogenicity and safety following administration of 2 HZ/su doses at intervals longer than 2 months. In this Phase III, open-label trial conducted in the US and Estonia, 354 adults ≥50 years were randomized 1:1:1 to receive 2 HZ/su doses 2, 6, or 12 months apart. gE-specific humoral immune responses were evaluated at pre-vaccination, 1 and 12 months post-dose 2. Co-primary objectives were to compare immune responses to HZ/su 1 month post-dose 2 when given 6-months or 12-months apart to those administered 2-months apart. For each participant, safety information was collected from dose 1 to 12 months post-dose 2. 346 participants completed the study and 343 were included in the according-to-protocol cohort for immunogenicity. One month post-dose 2, vaccine response rates were 96.5% (97.5% confidence interval [CI]: 90.4; 99.2) and 94.5% (97.5% CI: 87.6; 98.3) for the 0, 6- and 0, 12-month schedules, respectively, both schedules meeting the pre-defined criterion. Non-inferiority of anti-gE geometric mean concentrations was demonstrated for HZ/su administered on 0, 6-month compared to a 0, 2-month schedule; however, HZ/su administered on a 0, 12-month schedule did not meet the non-inferiority criterion. Injection site pain was the most commonly reported solicited adverse event (AE). 26 participants each reported at least 1 serious AE; none were assessed as related to vaccination. Immune responses to HZ/su administered at 0, 6-month were non-inferior to those elicited by a 0, 2-month schedule. HZ/su exhibited a clinically acceptable safety profile for all dosing intervals. Clinicaltrials.gov (NCT01751165

  19. Evaluation of preclinical single and multiple dose toxicity and efficacy of 213 Bi-labeled plasminogen activator inhibitor 2 for breast and prostate cancer

    International Nuclear Information System (INIS)

    Rizvi, S.; Li, Y.; Allen, B.; Littlejohn, T.; Ranson, M.; Links, M.; Irving, D.; Andrews, J.

    2003-01-01

    The aim of the study was to evaluate the single and multiple dose toxicity (maximum tolerated dose or MTD) regimes for 213 Bi-labeled PAI2. Dose range of 2-8 mCi/kg was used for the single dose toxicity studies. It was found that end point (20% weight loss and/or distressed behaviour) was not reached for the highest dose either with single or multiple dose injections. For multiple dose toxicity studies, the dose levels ranged between 0.4 - 2 mCi/kg, and were administered daily for 5 days. The highest level tested (2mCi/kg/day x 5) was the maximum tolerated dose as 3/6 mice succumbed to the endpoints. However, histological examination of major organs showed no adverse morphological changes. From these toxicity studies, we concluded that either a dose of 1.6mCi/kg of 213 Bi-PAI2 per day for 5 days or a single injection of 8 mCi/kg can be administered without reaching the endpoints. These dose levels were used for efficacy trials. The efficacy studies were conducted to examine if the 1.6mCi/kgday x 5 multiple dose schedule (sub-maximum tolerated dose) showed efficacy against established and early stage human breast and prostate tumours in mice. Statistical analyses of the data indicate a significant tumour growth rate delay and increased time to reach tumour size endpoint for alpha-PAI2 treatment compared to control tumours, in both pre-tumour stage and established tumour models

  20. Pharmacokinetic comparison of acetaminophen elixir versus suppositories in vaccinated infants (aged 3 to 36 months): a single-dose, open-label, randomized, parallel-group design.

    Science.gov (United States)

    Walson, Philip D; Halvorsen, Mark; Edge, James; Casavant, Marcel J; Kelley, Michael T

    2013-02-01

    Because of practical problems and ethical concerns, few studies of the pharmacokinetics (PK) of acetaminophen (ACET) in infants have been published. The goal of this study was to compare the PK of an ACET rectal suppository with a commercially available ACET elixir to complete a regulatory obligation to market the suppository. This study was not submitted previously because of numerous obstacles related to both the investigators and the commercial entities associated with the tested product. Thirty infants (age 3-36 months) prescribed ACET for either fever, pain, or postimmunization prophylaxis of fever and discomfort were randomized to receive a single 10- to 15-mg/kg ACET dose either as the rectal suppository or oral elixir. Blood was collected at selected times for up to 8 hours after administration. ACET concentrations were measured by using a validated HPLC method, and PK behavior and bioavailability were compared for the 2 preparations. All 30 infants enrolled were prescribed ACET for postimmunization prophylaxis. PK samples were available in 27 of the 30 enrolled infants. Subject enrollment (completed in January 1995) was rapid (8.3 months) and drawn entirely from a vaccinated infant clinic population. There were no statistically significant differences between the subjects (elixir, n = 12; suppository, n = 15) in either mean (SD) age (10.0 [6.3] vs 12.4 [8.1] months), weight (8.6 [2.3] vs 9.4 [2.4] kg), sex (7 of 12 males vs 7 of 15 males), or racial distribution (5 white, 5 black, and 2 biracial vs 4 white and 11 black) between the 2 dosing groups (oral vs rectal, respectively). The oral and rectal preparations produced similar, rapid peak concentrations (T(max), 1.16 vs 1.17 hours; P = 0.98) and elimination t(½) (1.84 vs 2.10 hours; P = 0.14), respectively. No statistically significant differences were found between either C(max) (7.65 vs 5.68 μg/mL) or total drug exposure (AUC(0-∞), 23.36 vs 20.45 μg-h/mL) for the oral versus rectal preparations

  1. 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression: Results of a phase III randomized multicentre Italian trial

    International Nuclear Information System (INIS)

    Maranzano, Ernesto; Trippa, Fabio; Casale, Michelina; Costantini, Sara; Lupattelli, Marco; Bellavita, Rita; Marafioti, Luigi; Pergolizzi, Stefano; Santacaterina, Anna; Mignogna, Marcello; Silvano, Giovanni; Fusco, Vincenzo

    2009-01-01

    Background and purpose: In a previous randomized trial we showed that the short-course radiotherapy (RT) regimen of 8 Gy x 2 was feasible in patients with metastatic spinal cord compression (MSCC) and short life expectancy. This phase III trial was planned to determine whether in the same category of patients 8 Gy single-dose is as effective as 8 Gy x 2. Materials and methods: Three hundred and twenty-seven patients with MSCC and short life expectancy were randomly assigned to a short-course of 8 Gy x 2 or to 8 Gy single-dose RT. Median follow-up was 31 months (range, 4-58). Results: A total of 303 (93%) patients are assessable, 150 treated with the short-course and 153 with the single-dose RT. No difference in response was found between the two RT schedules adopted. Median duration of response was 5 and 4.5 months for short-course and single-dose RT (p = 0.4), respectively. The median overall survival was 4 months for all cases. Light acute toxicity was registered in a minority of cases. Late toxicity was never recorded. Conclusions: Both RT schedules adopted were effective. As already shown in several trials evaluating RT regimens in uncomplicated painful bone metastases, also MSCC patients may achieve palliation with minimal toxicity and inconvenience with a single-dose of 8 Gy.

  2. Comparison of single-dose nalbuphine versus tramadol for postoperative pain management in children: a randomized, controlled trial.

    Science.gov (United States)

    Liaqat, Naeem; Dar, Sajid Hameed

    2017-04-01

    Acute postoperative pain control in children is an essential component of postoperative care, particularly in daycare procedures. Giving patients continuous narcotic analgesics can be risky; however, a single dose may be sufficient. This study used a prospective, randomized controlled design and was conducted at the Pediatric Surgery Unit, Services Hospital, Lahore. In total, 150 patients who underwent inguinal herniotomy (age range: 1-12 years) were randomly assigned to two groups: group A (nalbuphine) and group B (tramadol). Patients were given a single dose of either nalbuphine (0.2 mg/kg) or tramadol (2 mg/kg) immediately after surgery and pain was measured at 0, 1, 2, 4, and 8 h. The demographic characteristics were similar between the two groups. The mean pain score was lower in group A than in group B at 0 and 1 h (P pain scores in group A were still lower, but not significantly. In all, 9 patients (12.0%) required rescue analgesics in group A compared to 16 patients (21.3%) in group B (P = 0.051). The mean time for requirement of rescue analgesics was 6.5 ± 0.5 h in group A and 5.3 ± 1.7 h in group B (P = 0.06). A single dose of nalbuphine is sufficient, and superior to tramadol, for postoperative pain management in children who have undergone daycare procedures.

  3. Efficacy and safety of long-acting pasireotide in Japanese patients with acromegaly or pituitary gigantism: results from a multicenter, open-label, randomized, phase 2 study.

    Science.gov (United States)

    Tahara, Shigeyuki; Murakami, Mami; Kaneko, Tomomi; Shimatsu, Akira

    2017-07-28

    A multicenter, open-label, phase 2 study was conducted to investigate the efficacy and safety of long-acting pasireotide formulation in Japanese patients with acromegaly or pituitary gigantism. Medically naïve or inadequately controlled patients (on somatostatin analogues or dopamine agonists) were included. Primary end point was the proportion of all patients who achieved biochemical control (mean growth hormone [GH] levelsacromegaly, n=32; pituitary gigantism, n=1) were enrolled and randomized 1:1:1 to receive open-label pasireotide 20mg, 40mg, or 60mg. The median age was 52 years (range, 31-79) and 20 patients were males. At month 3, 18.2% of patients (6/33; 90% confidence interval: 8.2%, 32.8%) had biochemical control (21.2% [7/33] when including a patient with mean GHacromegaly or pituitary gigantism.

  4. Single-dose ceftriaxone for chancroid.

    Science.gov (United States)

    Bowmer, M I; Nsanze, H; D'Costa, L J; Dylewski, J; Fransen, L; Piot, P; Ronald, A R

    1987-01-01

    Men with genital ulcers that were culture positive for Haemophilus ducreyi were treated with intramuscular ceftriaxone and randomized to three different dose regimens. All but 1 of 50 men treated with 1 g of intramuscular ceftriaxone were cured. Similarly, 0.5 and 0.25 g cured 43 of 44 men and 37 of 38 men, respectively. A single dose of 250 mg of intramuscular ceftriaxone is an effective treatment for chancroid. PMID:3566241

  5. Generating Realistic Labelled, Weighted Random Graphs

    Directory of Open Access Journals (Sweden)

    Michael Charles Davis

    2015-12-01

    Full Text Available Generative algorithms for random graphs have yielded insights into the structure and evolution of real-world networks. Most networks exhibit a well-known set of properties, such as heavy-tailed degree distributions, clustering and community formation. Usually, random graph models consider only structural information, but many real-world networks also have labelled vertices and weighted edges. In this paper, we present a generative model for random graphs with discrete vertex labels and numeric edge weights. The weights are represented as a set of Beta Mixture Models (BMMs with an arbitrary number of mixtures, which are learned from real-world networks. We propose a Bayesian Variational Inference (VI approach, which yields an accurate estimation while keeping computation times tractable. We compare our approach to state-of-the-art random labelled graph generators and an earlier approach based on Gaussian Mixture Models (GMMs. Our results allow us to draw conclusions about the contribution of vertex labels and edge weights to graph structure.

  6. Comparison of idraparinux with vitamin K antagonists for prevention of thromboembolism in patients with atrial fibrillation: a randomised, open-label, non-inferiority trial

    DEFF Research Database (Denmark)

    Bousser, M.G.; Bouthier, J.; Buller, H.R.

    2008-01-01

    5.4) months because of excess clinically relevant bleeding with idraparinux (346 cases vs 226 cases; 19.7 vs 11.3 per 100 patient-years; pvitamin K antagonists (1.1 vs 0.4 per 100 patient-years; p=0......BACKGROUND: Vitamin K antagonists, the current standard treatment for prophylaxis against stroke and systemic embolism in patients with atrial fibrillation, require regular monitoring and dose adjustment; an unmonitored, fixed-dose anticoagulant regimen would be preferable. The aim...... of this randomised, open-label non-inferiority trial was to compare the efficacy and safety of idraparinux with vitamin K antagonists. METHODS: Patients with atrial fibrillation at risk for thromboembolism were randomly assigned to receive either subcutaneous idraparinux (2.5 mg weekly) or adjusted-dose vitamin K...

  7. Randomized trial of single dose versus fractionated palliative radiotherapy of bone metastases

    International Nuclear Information System (INIS)

    Nielsen, O.S.; Bentzen, S.M.; Sandberg, E.; Gadeberg, C.C.; Timothy, A.R.

    1998-01-01

    Purpose: Data in the literature suggest that for painful bone metastases a single dose is as effective as fractionated radiotherapy. In the present multicentre prospective trial, the effects of 8 Gy x1 and 5 Gy x4 were compared. Patients and methods: A total of 241 patients were randomized to 8 Gy (122 patients) or 20 Gy (119 patients). The primary tumour was in the breast in 39% of patients, in the prostate in 34% of patients, in the lung in 13% of patients and in other locations in 14% of patients. Outcome measures were pain relief as measured by VAS and in half of the patients also by a five-point categorical pain scale, global quality of life (QoL) and analgesic consumption. Evaluation was performed before and 4, 8, 12 and 20 weeks after treatment. Results: A total of 239 patients were evaluable for response. The two groups did not differ with respect to age, sex, primary tumour, metastasis localization, analgesic consumption (type and dose), performance status, prior systemic treatment, degree of pain and QoL. The treatment was completed as planned in 98% of patients. The degree of pain relief did not differ between the two treatment groups. At 4 weeks the difference in pain relief was 6% (95% CI 7, 20%) and at 8 weeks the difference was 13% (95% CI 3, 28%). Neither was there any significant difference in the duration of pain relief, the number of new painful sites and the need for reirradiation and toxicity was minor. Conclusion: The present randomized study showed that a single fraction of 8 Gy was as effective as 5 Gy x4 in relieving pain from bone metastasis. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  8. Low-Dose Total Skin Electron Beam Therapy as a Debulking Agent for Cutaneous T-Cell Lymphoma: An open-label prospective phase II study

    DEFF Research Database (Denmark)

    Kamstrup, M R; Lindahl, Lise Maria; Gniadecki, R

    2012-01-01

    Background: Total skin electron beam therapy (TSEBT) is a powerful treatment for cutaneous T-cell lymphomas (CTCL). Based on the occurrence of relapses with low radiation doses, doses of 30-36 Gy are commonly used but most patients still eventually relapse and repeat treatment courses are limited...... due to the cumulative toxicity. Complete response rates are about 60-90% for T2-4 stages with a 5-year relapse-free survival of 10-25% for stages IB-III. Objectives: To evaluate prospectively the efficacy of low-dose TSEBT (10 Gy) in terms of complete cutaneous response rate, overall response rate...... and response duration in CTCL. Methods: Ten patients with stage IB-IV mycosis fungoides (MF) were treated in an open-label manner with 4 fractions of 1 Gy/week TSEB to a total skin dose of 10 Gy. Treatment responses were assessed at 1 and 3 months after treatment and subsequently at least every 6 months...

  9. Inhibitory effects of intravenous lansoprazole 30 mg and pantoprazole 40 mg twice daily on intragastric acidity in healthy Chinese volunteers: a randomized, open-labeled, two-way crossover study.

    Science.gov (United States)

    Zhan, Xian-Bao; Guo, Xiao-Rong; Li, Zhao-Shen; Gong, Yan-Fang; Gao, Jun; Liao, Zhuan; Li, Zhen; Gao, Shen; Liu, Pei

    2012-02-01

    Until now there has been no study that directly compares the effect of lansoprazole and pantoprazole administered intravenously on intragastric acidity. The aim of this study is to compare the effect of lansoprazole (30 mg) and pantoprazole (40 mg) administered intravenously on gastric acidity. Helicobacter pylori-negative healthy volunteers were recruited in this open-label, randomized, two-way crossover, single centre study. Lansoprazole at 30 mg or pantoprazole at 40 mg was intravenously administered twice daily for 5 consecutive days with at least a 14-day washout interval. Twenty-four-hour intragastric pH was continuously monitored on days 1 and 5 of each dosing period. Twenty-five volunteers completed the 2 dosing periods. The mean intragastric pH values were higher in subjects treated with lansoprazole than those with pantoprazole on both day 1 (6.41 ± 0.14 vs. 5.49 ± 0.13, P=0.0003) and day 5 (7.09 ± 0.07 vs. 6.64 ± 0.07, P=0.0002). Significantly higher percentages of time with intragastric pH >4 and pH >6 were found in the subjects treated with lansoprazole than those with pantoprazole on day 1 (pH >4, 87.12 ± 4.55% vs. 62.28 ± 4.15%, P=0.0012; pH >6, 62.12 ± 4.12% vs. 47.25 ± 3.76%, P=0.0216) and pH >6 on day 5 (76.79 ± 3.77% vs. 58.20 ± 3.77%, P=0.0025). Intravenous lansoprazole produces a longer and more potent inhibitory effect on intragastric acidity than does intravenous pantoprazole.

  10. A preliminary path analysis of expectancy and patient-provider encounter in an open-label randomized controlled trial of spinal manipulation for cervicogenic headache.

    Science.gov (United States)

    Haas, Mitchell; Aickin, Mikel; Vavrek, Darcy

    2010-01-01

    The purpose of this article was to present a preliminary model to identify the effects of expectancy of treatment success and the patient-provider encounter (PPE) on outcomes in an open-label randomized trial. Eighty participants with chronic cervicogenic headache (CGH) were randomized to 4 groups: 2 levels of treatment dose (8 or 16) and 2 levels of therapy from a chiropractor (spinal manipulation or light massage). Providers were instructed to have equal enthusiasm for all care. Structural equation modeling with standardized path coefficients (beta) was used in a path analysis to identify the effects of patient expectancy and the PPE on CGH pain. The model included monthly pain from baseline to 12 weeks. Expectancy and PPE were evaluated on Likert scales. The patient-provider encounter was measured as patient perception of chiropractor enthusiasm, confidence, and comfort with care. Baseline patient expectancy was balanced across groups. The PPE measures were balanced across groups and consistent over the 8-week treatment period. Treatment and baseline pain had the strongest effects on pain outcomes (|beta| = .46-.59). Expectations had little effect on pain (abs value(beta) value(beta)= .03-.27) and on subsequent confidence in treatment success (abs value(beta)= .09 and .12). Encouraging equipoise in the PPE and balancing expectancy across treatment groups may protect against some confounding related to the absence of blinding in a randomized controlled trial of pain. In this trial, their effects were found to be small relative to the effects of treatment and baseline values. Copyright 2010 National University of Health Sciences. Published by Mosby, Inc. All rights reserved.

  11. An open-label, randomized, controlled, multicenter study exploring two treatment strategies of rivaroxaban and a dose-adjusted oral vitamin K antagonist treatment strategy in subjects with atrial fibrillation who undergo percutaneous coronary intervention (PIONEER AF-PCI).

    Science.gov (United States)

    Gibson, C Michael; Mehran, Roxana; Bode, Christoph; Halperin, Johnathan; Verheugt, Freek; Wildgoose, Peter; van Eickels, Martin; Lip, Gregory Y H; Cohen, Marc; Husted, Steen; Peterson, Eric; Fox, Keith

    2015-04-01

    Guidelines recommendations regarding anticoagulant therapy after percutaneous coronary intervention (PCI) among patients with atrial fibrillation (AF) rely on retrospective, nonrandomized observational data. Currently, patients are treated with triple-therapy (dual antiplatelet therapy [DAPT] + oral anticoagulation therapy), but neither the duration of DAPT nor the level of anticoagulation has been studied in a randomized fashion. Recent studies also suggest dual pathway therapy with clopidogrel plus oral anticoagulation therapy may be superior, and other studies suggest that novel oral anticoagulants such as rivaroxaban may further improve patient outcomes. PIONEER AF-PCI (ClinicalTrials.gov NCT01830543) is an exploratory, open-label, randomized, multicenter clinical study assessing the safety of 2 rivaroxaban treatment strategies and 1 vitamin K antagonist (VKA) treatment strategy in subjects who have paroxysmal, persistent, or permanent nonvalvular AF and have undergone PCI with stent placement. Approximately 2,100 subjects will be randomized in a 1:1:1 ratio to receive either rivaroxaban 15 mg once daily plus clopidogrel 75 mg daily for 12 months (a WOEST trial-like strategy), or rivaroxaban 2.5 mg twice daily (with stratification to a prespecified duration of DAPT 1, 6, or 12 months, an ATLAS trial-like strategy), or dose-adjusted VKA once daily (with stratification to a prespecified duration of DAPT 1, 6, or 12 months, traditional triple therapy). All patients will be followed up for 12 months for the primary composite end point of Thrombolysis in Myocardial Infarction major bleeding, bleeding requiring medical attention, and minor bleeding (collectively, clinically significant bleeding). The PIONEER AF-PCI study is the first randomized comparison of VKA vs novel oral anticoagulant therapy in patients with NVAF receiving antiplatelet therapy after PCI to assess the relative risks of bleeding complications. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Efficacy and safety of teneligliptin add-on to insulin monotherapy in Japanese patients with type 2 diabetes mellitus: a 16-week, randomized, double-blind, placebo-controlled trial with an open-label period.

    Science.gov (United States)

    Kadowaki, Takashi; Kondo, Kazuoki; Sasaki, Noriyuki; Miyayama, Kyoko; Yokota, Shoko; Terata, Ryuji; Gouda, Maki

    2017-09-01

    To assess the efficacy and safety of teneligliptin as add-on to insulin monotherapy in patients with type 2 diabetes mellitus (T2DM). In a 16-week, double-blind period, 148 Japanese T2DM patients with inadequate glycemic control with insulin and diet/exercise therapies were randomized to placebo or teneligliptin 20 mg. In a subsequent 36-week, open-label period, all patients received teneligliptin once daily. The primary outcome measure was change in HbA1c at the end of the double-blind period. The difference between placebo and teneligliptin in change in HbA1c in the double-blind period (least squares mean ± SE) was -0.80% ± 0.11%; teneligliptin was superior (ANCOVA, P 1). The HbA1c-lowering effect of teneligliptin was maintained throughout the open-label period. The incidence of adverse events was 53.5% with placebo and 44.2% with teneligliptin in the double-blind period, 66.7% in the placebo/teneligliptin group in the open-label period, and 77.9% in the teneligliptin/teneligliptin group over both double-blind/open-label periods. The incidence of hypoglycemic symptoms was 11.1% in the placebo/teneligliptin group in the open-label period and 27.3% in the teneligliptin/teneligliptin group over both double-blind/open-label periods. Teneligliptin was effective and well tolerated in Japanese T2DM patients with inadequate glycemic control. NCT02081599.

  13. Multi-Label Learning via Random Label Selection for Protein Subcellular Multi-Locations Prediction.

    Science.gov (United States)

    Wang, Xiao; Li, Guo-Zheng

    2013-03-12

    Prediction of protein subcellular localization is an important but challenging problem, particularly when proteins may simultaneously exist at, or move between, two or more different subcellular location sites. Most of the existing protein subcellular localization methods are only used to deal with the single-location proteins. In the past few years, only a few methods have been proposed to tackle proteins with multiple locations. However, they only adopt a simple strategy, that is, transforming the multi-location proteins to multiple proteins with single location, which doesn't take correlations among different subcellular locations into account. In this paper, a novel method named RALS (multi-label learning via RAndom Label Selection), is proposed to learn from multi-location proteins in an effective and efficient way. Through five-fold cross validation test on a benchmark dataset, we demonstrate our proposed method with consideration of label correlations obviously outperforms the baseline BR method without consideration of label correlations, indicating correlations among different subcellular locations really exist and contribute to improvement of prediction performance. Experimental results on two benchmark datasets also show that our proposed methods achieve significantly higher performance than some other state-of-the-art methods in predicting subcellular multi-locations of proteins. The prediction web server is available at http://levis.tongji.edu.cn:8080/bioinfo/MLPred-Euk/ for the public usage.

  14. Pharmacokinetics and Safety of DW1029M, a Botanical Drug for the Treatment of Diabetic Nephropathy, Following Single Doses in Healthy Subjects.

    Science.gov (United States)

    Kim, Yunjeong; Jeon, Ji-Young; Kim, Eun-Young; Lim, Cheol-Hee; Jang, Hwan Bong; Kim, Min-Gul

    2017-09-01

    DW1029M is a botanical extract of Morus albalinne root bark and Puerariae radix that is used for the treatment of diabetic nephropathy. This study evaluated the safety and pharmacokinetics of DW1029M following its administration in healthy Korean subjects. We conducted a randomized, open-label, single-dose, crossover phase 1 clinical study. During each period, subjects received 300, 600, or 1200 mg oral doses of DW1029M. Plasma concentrations of puerarin, daidzin, and daidzein were analyzed using a liquid chromatography-tandem mass spectrometry. Six healthy male subjects completed the study. The maximum concentration of the drug in the plasma (C max ) and area under the plasma drug concentration-time curve to the last measurable concentration (AUC last ) for puerarin, daidzin, and daidzein were assessed after oral administration of DW1029M. No serious adverse events or clinically or statistically significant adverse events associated with any of the drug levels were observed. The results of the measurement of vital signs, electrocardiogram, laboratory tests, and physical examinations indicated that no clinically significant changes occurred during this study. The DW1029M tablet was safe and well tolerated over a single dose range of 300-1200 mg. This pharmacokinetic study of a botanical drug may aid in the development of DW1029M. © 2017, The American College of Clinical Pharmacology.

  15. Single dose (400 mg) versus 7 day (200 mg) daily dose itraconazole in the treatment of tinea versicolor: a randomized clinical trial.

    Science.gov (United States)

    Wahab, M A; Ali, M E; Rahman, M H; Chowdhury, S A; Monamie, N S; Sultana, N; Khondoker, L

    2010-01-01

    Tinea (pityriasis) versicolor is a superficial fungal infection and one of the most commonly found pigmentary disorders of skin caused by the yeast Malassezia. Multiple topical as well as systemic therapies are available for treatment. Systemic therapies are used for extensive disease, frequent relapse or where topical agents have failed. The aim that translates the rationale of the study was to compare the efficacy, safety, tolerability and cost effectiveness of single dose 400mg versus 7 day 200 mg daily dose of itraconazole in the treatment of tinea versicolor. A clinical study was done to compare the efficacy of single dose (400 mg) of itraconazole and 7 day 200 mg daily dose of itraconazole in the treatment of extensive tinea versicolor. Total 60 patients (aged 18-50 years) were selected for the study during the period of June 2007 to May 2008 in the department of Dermatology of three different hospitals in Bangladesh. Cases having with extensive involvement, diagnosed clinically and confirmed by wood's lamp and KOH microscopy were taken. Patients were randomly allocated into equal groups. Group A was given single dose 400 mg itraconazole and Group B was given 7 day 200 mg daily itraconazole. Fifty three (88%) male and 7(12%) female were included in the study. The mean age of group A was 32.37+/-9 years and in group B 33.23+/-8 years. The mean duration of the disease in group A was 2.63+/-2 months and 2.76+/-2 months in group B. In group A clinical responders was found cure 22(73.33%) and improvement 5(16.33%) and in group B it was found cure 24(79.99%) and improvement 4(13.33%). The measure at the End point (EP1) equals to 90% response and in-group B it was found cure 24 (79.99%) and improvement 4(13.33%). (Here the End point EP2) equals to 93.33%. The EP clinical analysis however shows 91.66% response. Both single dose and 7 day daily dose of itraconazole can be effective in the treatment of tinea versicolor with extensive involvement but single dose appears

  16. The effect of single oral doses of duloxetine, reboxetine, and midodrine on the urethral pressure in healthy female subjects, using urethral pressure reflectometry

    DEFF Research Database (Denmark)

    Klarskov, Niels; Cerneus, Dirk; Sawyer, William

    2018-01-01

    AIMS: To evaluate the effect on urethral pressure of reference drugs known to reduce stress urinary incontinence symptoms by different effect size and mechanisms of action on urethral musculature under four test conditions in healthy female subjects using urethral pressure reflectometry. METHODS......: Healthy females aged 18-55 years were recruited by advertising for this phase 1, single site, placebo-controlled, randomized, four-period, crossover study. The interventions were single oral doses of 10 mg Midodrine, 80 mg Duloxetine, 12 mg Reboxetine, and placebo. The endpoints were the opening urethral...... pressure measured in each period at four time points (predose and 2, 5.5, and 9 h after dosing). RESULTS: Twenty-nine females were enrolled; 25 randomized and 24 completed the study. The opening urethral pressure was higher in all measurements with filled bladder compared with empty bladder, and during...

  17. Intravenous iron isomaltoside 1000 administered by high single-dose infusions or standard medical care for the treatment of fatigue in women after postpartum haemorrhage

    DEFF Research Database (Denmark)

    Holm, Charlotte; Thomsen, Lars Lykke; Norgaard, Astrid

    2015-01-01

    1000 with standard medical care on physical fatigue in women with postpartum haemorrhage. METHODS/DESIGN: In a single centre, open-labelled, randomised trial, women with postpartum haemorrhage exceeding 700 mL will be allocated to either a single dose of 1,200 mg of iron isomaltoside 1000 or standard...... Inventory. The primary objective will be considered to have been met if an intravenous high single dose of iron isomaltoside 1000 is shown to be superior to standard medical care in women after postpartum haemorrhage regarding physical fatigue.For claiming superiority, we set the minimal clinically relevant...... randomised controlled studies have compared the clinical efficacy and safety of standard medical care with intravenous administration of iron supplementation after postpartum haemorrhage.The primary objective of this study is to compare the efficacy of an intravenous high single-dose of iron isomaltoside...

  18. Benign painful shoulder syndrome. Initial results of a single-center prospective randomized radiotherapy dose-optimization trial

    International Nuclear Information System (INIS)

    Ott, O.J.; Hertel, S.; Gaipl, U.S.; Frey, B.; Schmidt, M.; Fietkau, R.

    2012-01-01

    Background and purpose: To compare the efficacy of two different dose-fractionation schedules for radiotherapy of patients with benign painful shoulder syndrome. Patients and methods: Between February 2006 and February 2010, 312 consecutive evaluable patients were recruited for this prospective randomized trial. All patients received radiotherapy with an orthovoltage technique. One radiotherapy course consisted of 6 single fractions in 3 weeks. In case of insufficient remission of pain after 6 weeks, a second radiation series was performed. Patients were randomly assigned to receive either single doses of 0.5 or 1.0 Gy. The endpoint was pain reduction. Pain was measured before, right after, and 6 weeks after radiotherapy using a visual analogue scale (VAS) and a comprehensive pain score (CPS). Results: The overall response rate for all patients was 83% directly after and 85% 6 weeks after radiotherapy. The mean VAS values before, directly after, and 6 weeks after treatment for the 0.5 and 1.0 Gy groups were 56.8 ± 23.7 and 53.2 ± 21.8 (p = 0.158), 38.2 ± 26.1 and 34.0 ± 24.5 (p = 0.189), and 33.0 ± 27.2 and 23.7 ± 22.7 (p = 0.044), respectively. The mean CPS before, directly after, and 6 weeks after treatment was 9.7 ± 3.0 and 9.5 ± 2.7 (p = 0.309), 6.1 ± 3.6 and 5.4 ± 3.6 (p = 0.096), 5.3 ± 3.7 and 4.1 ± 3.7 (p = 0.052), respectively. Despite a slight advantage in the VAS analysis for the 1.0 Gy group for delayed response, the CPS analysis revealed no statistically significant differences between the two single-dose trial arms for early (p = 0.652) and delayed response quality (p = 0.380). Conclusion: Radiotherapy is an effective treatment option for the management of benign painful shoulder syndrome. Concerning radiation protection, the dose for a radiotherapy series is recommended not to exceed 3-6 Gy. (orig.)

  19. Open-label extension studies: do they provide meaningful information on the safety of new drugs?

    Science.gov (United States)

    Day, Richard O; Williams, Kenneth M

    2007-01-01

    The number of open-label extension studies being performed has increased enormously in recent years. Often it is difficult to differentiate between these extension studies and the double-blind, controlled studies that preceded them. If undertaken primarily to gather more patient-years of exposure to the new drug in order to understand and gain confidence in its safety profile, open-label extension studies can play a useful and legitimate role in drug development and therapeutics. However, this can only occur if the open-label extension study is designed, executed, analysed and reported competently. Most of the value accrued in open-label extension studies is gained from a refinement in the perception of the expected incidence of adverse effects that have most likely already been identified as part of the preclinical and clinical trial programme. We still have to rely heavily on post-marketing safety surveillance systems to alert us to type B (unpredictable) adverse reactions because open-label extension studies are unlikely to provide useful information about these types of often serious and relatively rare adverse reactions. Random allocation into test and control groups is needed to produce precise incidence data on pharmacologically expected, or type A, adverse effects. Some increased confidence about incidence rates might result from the open-label extension study; however, as these studies are essentially uncontrolled and biased, the data are not of great value. Other benefits have been proposed to be gained from open-label extension studies. These include ongoing access to an effective but otherwise unobtainable medicine by the volunteers who participated in the phase III pivotal trials. However, there are unappreciated ethical issues about the appropriateness of enrolling patients whose response to previous treatment is uncertain, largely because treatment allocation in the preceding randomised, double-blind, controlled trial has not been revealed at the

  20. Synergistic effects of total ionizing dose on single event upset sensitivity in static random access memory under proton irradiation

    International Nuclear Information System (INIS)

    Xiao Yao; Guo Hong-Xia; Zhang Feng-Qi; Zhao Wen; Wang Yan-Ping; Zhang Ke-Ying; Ding Li-Li; Luo Yin-Hong; Wang Yuan-Ming; Fan Xue

    2014-01-01

    Synergistic effects of the total ionizing dose (TID) on the single event upset (SEU) sensitivity in static random access memories (SRAMs) were studied by using protons. The total dose was cumulated with high flux protons during the TID exposure, and the SEU cross section was tested with low flux protons at several cumulated dose steps. Because of the radiation-induced off-state leakage current increase of the CMOS transistors, the noise margin became asymmetric and the memory imprint effect was observed. (interdisciplinary physics and related areas of science and technology)

  1. An Open-Label, Phase 1 Study to Assess the Effects of Hepatic Impairment on Pomalidomide Pharmacokinetics.

    Science.gov (United States)

    Li, Yan; Wang, Xiaomin; Liu, Liangang; Zhang, Chengyue; Gomez, Diana; Reyes, Josephine; Palmisano, Maria; Zhou, Simon

    2018-05-10

    Pomalidomide is an immunomodulatory drug and the dosage of 4 mg per day taken orally on days 1-21 of repeated 28-day cycles has been approved in the European Union and United States to treat patients with relapsed/refractory multiple myeloma. Because pomalidomide is extensively metabolized prior to excretion, a total of 32 subjects (8 healthy subjects in group 1; 8 subjects with severe hepatic impairment in group 2; 8 subjects with moderate hepatic impairment in group 3; and 8 subjects with mild hepatic impairment in group 4) were enrolled in a multicenter, open-label, single-dose study to assess the impact of hepatic impairment on pomalidomide exposure. Following administration of a single oral dose of 4-mg pomalidomide, the geometric mean ratios of pomalidomide total plasma exposures (AUC) were 171.5%, 157.5%, and 151.2% and the geometric mean ratios of pomalidomide plasma peak exposures (C max ) were 75.8%, 94.8%, and 94.2% for subjects with severe, moderate, or mild hepatic impairment, respectively, versus healthy subjects. Pomalidomide administered as a single oral 4-mg dose was safe and well tolerated by healthy subjects and subjects with severe, moderate, or mild hepatic impairment. Based on the pharmacokinetic results from this study, the pomalidomide prescribing information approved by the US Food and Drug Administration recommends for patients with mild or moderate hepatic impairment (Child-Pugh classes A or B), a 3-mg starting daily dose (25% dose reduction) and for patients with severe hepatic impairment (Child-Pugh class C), a 2-mg starting daily dose (50% dose reduction). © 2018 The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.

  2. Busulfan and melphalan versus carboplatin, etoposide, and melphalan as high-dose chemotherapy for high-risk neuroblastoma (HR-NBL1/SIOPEN): an international, randomised, multi-arm, open-label, phase 3 trial.

    Science.gov (United States)

    Ladenstein, Ruth; Pötschger, Ulrike; Pearson, Andrew D J; Brock, Penelope; Luksch, Roberto; Castel, Victoria; Yaniv, Isaac; Papadakis, Vassilios; Laureys, Geneviève; Malis, Josef; Balwierz, Walentyna; Ruud, Ellen; Kogner, Per; Schroeder, Henrik; de Lacerda, Ana Forjaz; Beck-Popovic, Maja; Bician, Pavel; Garami, Miklós; Trahair, Toby; Canete, Adela; Ambros, Peter F; Holmes, Keith; Gaze, Mark; Schreier, Günter; Garaventa, Alberto; Vassal, Gilles; Michon, Jean; Valteau-Couanet, Dominique

    2017-04-01

    High-dose chemotherapy with haemopoietic stem-cell rescue improves event-free survival in patients with high-risk neuroblastoma; however, which regimen has the greatest patient benefit has not been established. We aimed to assess event-free survival after high-dose chemotherapy with busulfan and melphalan compared with carboplatin, etoposide, and melphalan. We did an international, randomised, multi-arm, open-label, phase 3 cooperative group clinical trial of patients with high-risk neuroblastoma at 128 institutions in 18 countries that included an open-label randomised arm in which high-dose chemotherapy regimens were compared. Patients (age 1-20 years) with neuroblastoma were eligible to be randomly assigned if they had completed a multidrug induction regimen (cisplatin, carboplatin, cyclophosphamide, vincristine, and etoposide with or without topotecan, vincristine, and doxorubicin) and achieved an adequate disease response. Patients were randomly assigned (1:1) to busulfan and melphalan or to carboplatin, etoposide, and melphalan by minimisation, balancing age at diagnosis, stage, MYCN amplification, and national cooperative clinical group between groups. The busulfan and melphalan regimen comprised oral busulfan (150 mg/m 2 given on 4 days consecutively in four equal doses); after Nov 8, 2007, intravenous busulfan was given (0·8-1·2 mg/kg per dose for 16 doses according to patient weight). After 24 h, an intravenous melphalan dose (140 mg/m 2 ) was given. Doses of busulfan and melphalan were modified according to bodyweight. The carboplatin, etoposide, and melphalan regimen consisted of carboplatin continuous infusion of area under the plasma concentration-time curve 4·1 mg/mL per min per day for 4 days, etoposide continuous infusion of 338 mg/m 2 per day for 4 days, and melphalan 70 mg/m 2 per day for 3 days, with doses for all three drugs modified according to bodyweight and glomerular filtration rate. Stem-cell rescue was given after the last dose of

  3. A Multicentric, Open-Label, Randomized, Comparative Clinical Trial of Two Different Doses of Expanded hBM-MSCs Plus Biomaterial versus Iliac Crest Autograft, for Bone Healing in Nonunions after Long Bone Fractures: Study Protocol

    Directory of Open Access Journals (Sweden)

    Enrique Gómez-Barrena

    2018-01-01

    Full Text Available ORTHOUNION is a multicentre, open, comparative, three-arm, randomized clinical trial (EudraCT number 2015-000431-32 to compare the efficacy, at one and two years, of autologous human bone marrow-derived expanded mesenchymal stromal cell (hBM-MSC treatments versus iliac crest autograft (ICA to enhance bone healing in patients with diaphyseal and/or metaphysodiaphyseal fracture (femur, tibia, and humerus status of atrophic or oligotrophic nonunion (more than 9 months after the acute fracture, including recalcitrant cases after failed treatments. The primary objective is to determine if the treatment with hBM-MSCs combined with biomaterial is superior to ICA in obtaining bone healing. If confirmed, a secondary objective is set to determine if the dose of 100 × 106 hBM-MSCs is noninferior to that of 200 × 106 hBM-MSCs. The participants (n=108 will be randomly assigned to either the experimental low dose (n=36, the experimental high dose (n=36, or the comparator arm (n=36 using a central randomization service. The trial will be conducted in 20 clinical centres in Spain, France, Germany, and Italy under the same clinical protocol. The confirmation of superiority for the proposed ATMP in nonunions may foster the future of bone regenerative medicine in this indication. On the contrary, absence of superiority may underline its limitations in clinical use.

  4. A Multicentric, Open-Label, Randomized, Comparative Clinical Trial of Two Different Doses of Expanded hBM-MSCs Plus Biomaterial versus Iliac Crest Autograft, for Bone Healing in Nonunions after Long Bone Fractures: Study Protocol.

    Science.gov (United States)

    Gómez-Barrena, Enrique; Padilla-Eguiluz, Norma G; Avendaño-Solá, Cristina; Payares-Herrera, Concepción; Velasco-Iglesias, Ana; Torres, Ferran; Rosset, Philippe; Gebhard, Florian; Baldini, Nicola; Rubio-Suarez, Juan C; García-Rey, Eduardo; Cordero-Ampuero, José; Vaquero-Martin, Javier; Chana, Francisco; Marco, Fernando; García-Coiradas, Javier; Caba-Dessoux, Pedro; de la Cuadra, Pablo; Hernigou, Philippe; Flouzat-Lachaniette, Charles-Henri; Gouin, François; Mainard, Didier; Laffosse, Jean Michel; Kalbitz, Miriam; Marzi, Ingo; Südkamp, Norbert; Stöckle, Ulrich; Ciapetti, Gabriela; Donati, Davide Maria; Zagra, Luigi; Pazzaglia, Ugo; Zarattini, Guido; Capanna, Rodolfo; Catani, Fabio

    2018-01-01

    ORTHOUNION is a multicentre, open, comparative, three-arm, randomized clinical trial (EudraCT number 2015-000431-32) to compare the efficacy, at one and two years, of autologous human bone marrow-derived expanded mesenchymal stromal cell (hBM-MSC) treatments versus iliac crest autograft (ICA) to enhance bone healing in patients with diaphyseal and/or metaphysodiaphyseal fracture (femur, tibia, and humerus) status of atrophic or oligotrophic nonunion (more than 9 months after the acute fracture, including recalcitrant cases after failed treatments). The primary objective is to determine if the treatment with hBM-MSCs combined with biomaterial is superior to ICA in obtaining bone healing. If confirmed, a secondary objective is set to determine if the dose of 100 × 10 6 hBM-MSCs is noninferior to that of 200 × 10 6 hBM-MSCs. The participants ( n = 108) will be randomly assigned to either the experimental low dose ( n = 36), the experimental high dose ( n = 36), or the comparator arm ( n = 36) using a central randomization service. The trial will be conducted in 20 clinical centres in Spain, France, Germany, and Italy under the same clinical protocol. The confirmation of superiority for the proposed ATMP in nonunions may foster the future of bone regenerative medicine in this indication. On the contrary, absence of superiority may underline its limitations in clinical use.

  5. Relative oral bioavailability of morphine and naltrexone derived from crushed morphine sulfate and naltrexone hydrochloride extended-release capsules versus intact product and versus naltrexone solution: a single-dose, randomized-sequence, open-label, three-way crossover trial in healthy volunteers.

    Science.gov (United States)

    Johnson, Franklin K; Stark, Jeffrey G; Bieberdorf, Frederick A; Stauffer, Joe

    2010-06-01

    Morphine sulfate/sequestered naltrexone hydrochloride (HCl) (MS-sNT) extended-release fixed-dose combination capsules, approved by the US Food and Drug Administration (FDA) in August 2009 for chronic moderate to severe pain, contain extended-release morphine pellets with a sequestered core of the opioid antagonist naltrexone. MS-sNT was designed so that if the product is tampered with by crushing, the naltrexone becomes bioavailable to mitigate morphine-induced subjective effects, rendering the product less attractive for tampering. The primary aim of this study was to compare the oral bioavailability of naltrexone and its metabolite 6-beta-naltrexol, derived from crushed pellets from MS-sNT capsules, to naltrexone solution. This study also assessed the relative bioavailability of morphine from crushed pellets from MS-sNT capsules and that from the whole, intact product. This single-dose, randomized-sequence, open-label, 3-period, 3-treatment crossover trial was conducted in healthy volunteers. Adults admitted to the study center underwent a 10-hour overnight fast before study drug administration. Each subject received all 3 of the following treatments, 1 per session, separated by a 14-day washout: tampered pellets (crushed for >or=2 minutes with a mortar and pestle) from a 60-mg MS-sNT capsule (60 mg morphine/2.4 mg naltrexone); 60-mg whole, intact MS-sNT capsule; and oral naltrexone HCl (2.4 mg) solution. Plasma concentrations of naltrexone and 6-beta-naltrexol were measured 0 to 168 hours after administration. Morphine pharmaco-kinetics of crushed and whole pellets were determined 0 to 72 hours after administration. The analysis of relative bioavailability was based on conventional FDA criteria for assuming bioequivalence; that is, 90% CIs for ratios of geometric means (natural logarithm [In]-transformed C(max) and AUC) fell within the range of 80% to 125%. Subjects underwent physical examinations, clinical laboratory tests, and ECG at screening and study

  6. A Cohort Study of Preoperative Single Dose Versus Four Doses of Antibiotics for Patients With Non-Complicated Acute Appendicitis

    Directory of Open Access Journals (Sweden)

    Salah H. Al Janaby

    2017-02-01

    Full Text Available Objective: To Test the efficacy of single preoperative dose of Cefotaxime 1gm and Metronidazole 500mg in reducing the surgical site infections (SSIs after open appendectomy in patients with non-complicated appendicitis (NCA Place and Duration of Study: Al Hilla General Teaching Hospital, Babel Governorate-Iraq, from January 2013 to January 2014. Patients & Methods: 100 patients, who underwent appendectomy for NCA and fulfilled the selection criteria, were randomized into two groups. The patients in group A received a single dose of pre-operative antibiotics (Cefotaxime sodium and metronidazole, while the group B patients received three more dose of the same antibiotics postoperatively. Patients of both groups were followed-up for 30 days to assess the postoperative infective complications. Results: Group A had 48, while group B comprised of 52 patients. The groups were comparable in the baseline characteristics. Statistically, P value in rates of SSIs between both the groups was 0.9182. None of the patients developed intra-abdominal collection. Conclusion: Single dose of pre-operative antibiotics (Cefotaxime and metronidazole was sufficient in reducing the SSIs after appendectomy for NPA. Postoperative antibiotics did not add an appreciable clinical benefit in these patients. Key words: Preoperative antibiotics, Appendectomy, Surgical site infection, Non-complicated appendicitis Abbreviations: SSI: Surgical Site Infection, NCA: non-complicated appendicitis CDC Center of Disease Control.

  7. Immunogenicity and safety of purified chick-embryo cell rabies vaccine under Zagreb 2-1-1 or 5-dose Essen regimen in Chinese children 6 to 17 years old and adults over 50 years: a randomized open-label study.

    Science.gov (United States)

    Li, RongCheng; Li, YanPing; Wen, ShuQing; Wen, HuiChun; Nong, Yi; Mo, Zhaojun; Xie, Fang; Pellegrini, Michele

    2015-01-01

    The aim of this Phase IIIb, open-label, randomized study was to demonstrate the non-inferiority of immune responses and to assess the safety of a purified chick-embryo cell rabies vaccine (PCECV) in healthy Chinese children (6 to 17 years) and older adults (≥51 years) following 2 alternative intramuscular (IM) simulated post-exposure prophylaxis (PEP) regimens: 4-dose Zagreb or 5-dose Essen regimen. Serum samples were collected prior to vaccination on Days 1 and 15 and on day 43 to assess immune response by rabies virus neutralizing antibody (RVNA) concentrations. Solicited adverse events (AEs) were recorded for up to 7 days following each vaccine dose, and unsolicited AEs throughout the entire study period. PCECV vaccination induced a strong immune response at Day 15, and the non-inferiority in immune response of the Zagreb vs. the Essen regimen was demonstrated in children and older adults. At Day 15,100% of children (N = 224), and 99% of subjects ≥51 years of age (N = 376) developed adequate RVNA concentrations (≥0.5 IU/mL); at Day 43 all subjects achieved RVNA concentrations ≥0.5 IU/mL, for both PEP regimens. The well-known tolerability and safety profile of the PCECV was again observed in this study following either Zagreb or Essen regimens. Rabies PEP vaccination with PCECV following a Zagreb regimen induced immune responses non-inferior to those of the Essen regimen, and had a similar safety and tolerability profile to the Essen regimen in Chinese children, adolescents, and adults over 51 years. ClinicalTrials.gov identifier: NCT01680016.

  8. An open-label, dose-titration tolerability study of atomoxetine hydrochloride in Japanese adults with attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Takahashi, Michihiro; Takita, Yasushi; Goto, Taro; Ichikawa, Hironobu; Saito, Kazuhiko; Matsumoto, Hideo; Tanaka, Yasuo

    2011-02-01

    The main purpose of this first atomoxetine study in Japanese adults with attention-deficit/hyperactivity disorder (ADHD) was to investigate the tolerability of an 8-week treatment regimen. This was an open-label, dose escalation study conducted in 45 Japanese patients aged at least 18 years with DSM-IV-defined ADHD. Patients received atomoxetine orally for 8 weeks. Atomoxetine administration was started at 40 mg/day (7 days), and subsequently increased to a maximum dose of 120 mg/day. Tolerability was assessed by discontinuation rate due to adverse events. Adverse events, laboratory tests, vital signs and electrocardiograms were collected. In addition, ADHD symptoms were assessed by using the Japanese version of the Conners' Adult ADHD Rating Scale-Investigator Rated: Screening Version (CAARS-Inv:SV) scores. Thirty-nine patients completed the study period. Atomoxetine was well tolerated with a 6.7% (3/45) discontinuation rate due to nausea, malaise and anorexia. The most commonly reported adverse events were nausea, nasopharyngitis and headache; there were no unexpected safety concerns. No deaths or serious adverse events were reported. Mean CAARS-Inv:SV-J total ADHD symptom scores decreased in a time-dependent manner; the mean change from baseline to endpoint was -15.0 (Patomoxetine was well tolerated in these patients and suggested that atomoxetine at a maximum dose of 120 mg/day would be safe in Japanese ADHD patients. © 2011 The Authors. Psychiatry and Clinical Neurosciences © 2011 Japanese Society of Psychiatry and Neurology.

  9. Treatment of asymptomatic vaginal candidiasis in pregnancy to prevent preterm birth: an open-label pilot randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Rickard Kristen

    2011-03-01

    Full Text Available Abstract Background Although the connection between ascending infection and preterm birth is undisputed, research focused on finding effective treatments has been disappointing. However evidence that eradication of Candida in pregnancy may reduce the risk of preterm birth is emerging. We conducted a pilot study to assess the feasibility of conducting a large randomized controlled trial to determine whether treatment of asymptomatic candidiasis in early pregnancy reduces the incidence of preterm birth. Methods We used a prospective, randomized, open-label, blinded-endpoint (PROBE study design. Pregnant women presenting at Candida were randomized to 6-days of clotrimazole vaginal pessaries (100mg or usual care (screening result is not revealed, no treatment. The primary outcomes were the rate of asymptomatic vaginal candidiasis, participation and follow-up. The proposed primary trial outcome of spontaneous preterm birth Results Of 779 women approached, 500 (64% participated in candidiasis screening, and 98 (19.6% had asymptomatic vaginal candidiasis and were randomized to clotrimazole or usual care. Women were not inconvenienced by participation in the study, laboratory testing and medication dispensing were problem-free, and the follow-up rate was 99%. There was a tendency towards a reduction in spontaneous preterm birth among women with asymptomatic candidiasis who were treated with clotrimazole RR = 0.33, 95%CI 0.04-3.03. Conclusions A large, adequately powered, randomized trial of clotrimazole to prevent preterm birth in women with asymptomatic candidiasis is both feasible and warranted. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR: ACTRN12609001052224

  10. Single-dose pharmacokinetic study comparing the pharmacokinetics of recombinant human chorionic gonadotropin in healthy Japanese and Caucasian women and recombinant human chorionic gonadotropin and urinary human chorionic gonadotropin in healthy Japanese women.

    Science.gov (United States)

    Bagchus, Wilhelmina; Wolna, Peter; Uhl, Wolfgang

    2018-01-01

    Recombinant hCG (r-hCG) was approved in Japan in 2016. As a prerequisite for a Phase III study in Japan related to this approval, the pharmacokinetic (PK) profile of r-hCG was investigated. An open-label, partly randomized, single-center, single-dose, group-comparison, Phase I PK-bridging study was done that compared a single 250 μg dose of r-hCG with a single 5000 IU dose of urinary hCG (u-hCG) in healthy Japanese women, as well as comparing a single 250 μg dose of r-hCG in Japanese and Caucasian women. The Japanese participants were randomized 1:1 to receive either r-hCG or u-hCG, while the Caucasian participants were weight-matched to the Japanese participants who were receiving r-hCG in a 1:1 fashion. The primary PK parameters were the area under the serum concentration-time curve from time 0 extrapolated to infinity (AUC 0-∞ ) and the maximum serum concentration (C max ). The mean serum hCG concentration-time profiles of r-hCG in the Japanese and Caucasian participants were a similar shape, but the level of overall exposure was ~20% lower in the Japanese participants. For the Japanese participants, r-hCG resulted in an 11% lower C max but a 19% higher AUC 0-∞ compared with u-hCG. No new safety signal was identified. This study cannot exclude a potential difference in the PK profile of r-hCG between Japanese and Caucasian participants. However, this study does not indicate that there are clinically relevant differences in the serum PK of r-hCG and u-hCG in the Japanese participants.

  11. A Complex Multiherbal Regimen Based on Ayurveda Medicine for the Management of Hepatic Cirrhosis Complicated by Ascites: Nonrandomized, Uncontrolled, Single Group, Open-Label Observational Clinical Study.

    Science.gov (United States)

    Patel, Manish V; Patel, Kalapi B; Gupta, Shivenarain; Michalsen, Andreas; Stapelfeldt, Elmar; Kessler, Christian S

    2015-01-01

    Hepatic cirrhosis is one of the leading causes of death worldwide, especially if complicated by ascites. This chronic condition can be related to the classical disease entity jalodara in Traditional Indian Medicine (Ayurveda). The present paper aims to evaluate the general potential of Ayurvedic therapy for overall clinical outcomes in hepatic cirrhosis complicated by ascites (HCcA). In form of a nonrandomized, uncontrolled, single group, open-label observational clinical study, 56 patients fulfilling standardized diagnostic criteria for HCcA were observed during their treatment at the P. D. Patel Ayurveda Hospital, Nadiad, India. Based on Ayurvedic tradition, a standardized treatment protocol was developed and implemented, consisting of oral administration of single and compound herbal preparations combined with purificatory measures as well as dietary and lifestyle regimens. The outcomes were assessed by measuring liver functions through specific clinical features and laboratory parameters and by evaluating the Child-Pugh prognostic grade score. After 6 weeks of treatment and a follow-up period of 18 weeks, the outcomes showed statistically significant and clinically relevant improvements. Further larger and randomized trials on effectiveness, safety, and quality of the Ayurvedic approach in the treatment of HCcA are warranted to support these preliminary findings.

  12. A randomized treatment trial: single versus 7-day dose of metronidazole for the treatment of Trichomonas vaginalis among HIV-infected women.

    Science.gov (United States)

    Kissinger, Patricia; Mena, Leandro; Levison, Judy; Clark, Rebecca A; Gatski, Megan; Henderson, Harold; Schmidt, Norine; Rosenthal, Susan L; Myers, Leann; Martin, David H

    2010-12-15

    To determine if the metronidazole (MTZ) 2-gm single dose (recommended) is as effective as the 7-day 500 mg twice a day dose (alternative) for treatment of Trichomonas vaginalis (TV) among HIV+ women. Phase IV randomized clinical trial; HIV+ women with culture confirmed TV were randomized to treatment arm: MTZ 2-gm single dose or MTZ 500 mg twice a day 7-day dose. All women were given 2-gm MTZ doses to deliver to their sex partners. Women were recultured for TV at a test-of-cure (TOC) visit occurring 6-12 days after treatment completion. TV-negative women at TOC were again recultured at a 3-month visit. Repeat TV infection rates were compared between arms. Two hundred seventy HIV+/TV+ women were enrolled (mean age = 40 years, ±9.4; 92.2% African American). Treatment arms were similar with respect to age, race, CD4 count, viral load, antiretroviral therapy status, site, and loss-to-follow up. Women in the 7-day arm had lower repeat TV infection rates at TOC [8.5% (11 of 130) versus 16.8% (21 of 125) (relative risk: 0.50, 95% confidence interval = 0.25, 1.00; P TV among HIV+ women.

  13. Effect of mouth cleaning with hinokitiol-containing gel on oral malodor: a randomized, open-label pilot study.

    Science.gov (United States)

    Iha, Kosaku; Suzuki, Nao; Yoneda, Masahiro; Takeshita, Toru; Hirofuji, Takao

    2013-10-01

    The aim of the study was to evaluate the effect of mouth cleaning with hinokitiol-containing gel on oral malodor. An open-label, randomized, controlled trial was conducted to assess oral malodor and clinical parameters related to oral malodor before and after mouth cleaning with hinokitiol-containing gel (n = 9) or with gel not including hinokitiol (n = 9). Mouth cleaning included the teeth, gingiva, and tongue and was carried out 3 times per day for 4 weeks. Organoleptic test (OLT) scores (P = .021), levels of hydrogen sulfide (P = .008) and methyl mercaptan (P = .020), frequency of bleeding on probing, average probing pocket depth, and plaque index significantly improved in the group using hinokitiol. In contrast, only the OLT score (P = .031) significantly improved in the control group after the treatment regimen. Mouth cleaning with hinokitiol-containing gel may be effective for reduction of oral malodor. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Bioequivalence of fixed-dose combination RIN®-150 to each reference drug in loose combination.

    Science.gov (United States)

    Wang, H F; Wang, R; O'Gorman, M; Crownover, P; Damle, B

    2015-03-01

    RIN(®)-150 is a fixed-dose combination (FDC) tablet containing rifampicin (RMP, 150 mg) and isoniazid (INH, 75 mg) developed for the treatment of tuberculosis. This study was conducted at a single center: the Pfizer Clinical Research Unit in Singapore. To demonstrate bioequivalence of each drug component between RIN-150 and individual products in a loose combination. This was a randomized, open-label, single-dose, two-way crossover study. Subjects received single doses of RIN-150 or two individual reference products under fasting conditions in a crossover fashion, with at least 7 days washout between doses. The primary measures for comparison were peak plasma concentration (Cmax) and the area under plasma concentration-time curve (AUC). Of 28 subjects enrolled, 26 completed the study. The adjusted geometric mean ratios of Cmax and AUClast between the FDC and single-drug references and 90% confidence intervals were respectively 91.63% (90%CI 83.13-101.01) and 95.45% (90%CI 92.07-98.94) for RMP, and 107.58% (90%CI 96.07-120.47) and 103.45% (90%CI 99.33-107.75) for INH. Both formulations were generally well tolerated in this study. The RIN-150 FDC tablet formulation is bioequivalent to the two single-drug references for RMP and INH at equivalent doses.

  15. Foley Catheter for Induction of Labor at Term: An Open-Label, Randomized Controlled Trial.

    Directory of Open Access Journals (Sweden)

    Ning Gu

    Full Text Available This study aimed to determine the optimal Foley catheter balloon volume (30-mL vs. 80-mL and the maximum time for cervical ripening (12 hours vs. 24 hours to improve vaginal delivery rate within 24 hours of induction.We conducted an open-label, randomized controlled trial in a teaching hospital in China. Women with a term singleton pregnancy, cephalic presentation, intact membrane and an unfavorable cervix (Bishop score <6 were randomly allocated, in 1:1:1:1 ratio, to receive either one of the four treatments: (1 30-mL balloon for a maximum of 12 hours, (2 30-mL balloon for a maximum of 24 hours, (3 80-mL balloon for a maximum of 12 hours, and (4 80-mL balloon for a maximum of 24 hours. The primary outcome was vaginal delivery within 24 hours. Secondary outcomes included cesarean section rate and maternal/neonatal morbidity. Data were analyzed on a per-protocol basis.Five hundred and four women were recruited and randomized (126 women in each group; nine women did not receive the assigned intervention. More women achieved vaginal delivery within 24 hours in 12-hour Foley catheter groups than in the 24-hour Foley catheter groups (30-mL/12 hours: 54.5%, 30-mL/24 hours: 33.1%, 80-mL/12 hours: 46.4%, 80-mL/24 hours: 24.0%, p < 0.001. Cesarean section rates and the incidence of chorioaminonitis were comparable among four groups. After adjustment for confounding factors, both ripening time and balloon size did not affect the proportion of women delivered vaginally within 24 hours of induction.For women with an unfavorable cervix at term, induction of labor with a Foley catheter is safe and effective. Higher balloon volume (80-mL vs. 30-mL and longer ripening time (24 hours vs. 12 hours would not shorten induction to delivery interval or reduce cesarean section rate.Chinese Clinical trial registry (ChiCTR-TRC-13003044.

  16. DRY CUPPING IN CHILDREN WITH FUNCTIONAL CONSTIPATION: A RANDOMIZED OPEN LABEL CLINICAL TRIAL.

    Science.gov (United States)

    Shahamat, Mahmoud; Daneshfard, Babak; Najib, Khadijeh-Sadat; Dehghani, Seyed Mohsen; Tafazoli, Vahid; Kasalaei, Afshineh

    2016-01-01

    As a common disease in pediatrics, constipation poses a high burden to the community. In this study, we aimed to investigate the efficacy of dry cupping therapy (an Eastern traditional manipulative therapy) in children with functional constipation. One hundred and twenty children (4-18 years old) diagnosed as functional constipation according to ROME III criteria were assigned to receive a traditional dry cupping protocol on the abdominal wall for 8 minutes every other day or standard laxative therapy (Polyethylene glycol (PEG) 40% solution without electrolyte), 0.4 g/kg once daily) for 4 weeks, in an open label randomized controlled clinical trial using a parallel design with a 1:1 allocation ratio. Patients were evaluated prior to and following 2, 4, 8 and 12 weeks of the intervention commencement in terms of the ROME III criteria for functional constipation. There were no significant differences between the two arms regarding demographic and clinical basic characteristics. After two weeks of the intervention, there was a significant better result in most of the items of ROME III criteria of patients in PEG group. In contrast, after four weeks of the intervention, the result was significantly better in the cupping group. There was no significant difference in the number of patients with constipation after 4 and 8 weeks of the follow-up period. This study showed that dry cupping of the abdominal wall, as a traditional manipulative therapy, can be as effective as standard laxative therapy in children with functional constipation.

  17. Single-larger-portion-size and dual-column nutrition labeling may help consumers make more healthful food choices.

    Science.gov (United States)

    Lando, Amy M; Lo, Serena C

    2013-02-01

    The Food and Drug Administration is considering changes to the Nutrition Facts label to help consumers make more healthful choices. To examine the effects of modifications to the Nutrition Facts label on foods that can be listed as having 1 or 2 servings per container, but are reasonably consumed at a single eating occasion. Participants were randomly assigned to study conditions that varied on label format, product, and nutrition profile. Data were collected via an online consumer panel. Adults aged 18 years and older were recruited from Synovate's online household panel. Data were collected during August 2011. A total of 32,897 invitations were sent for a final sample of 9,493 interviews. Participants were randomly assigned to one of 10 label formats classified into three groups: listing 2 servings per container with a single column, listing 2 servings per container with a dual column, and listing a single serving per container. Within these groups there were versions that enlarged the font size for "calories," removed "calories from fat," and changed the wording for serving size declaration. The single product task measured product healthfulness, the amount of calories and various nutrients per serving and per container, and label perceptions. The product comparison task measured ability to identify the healthier product and the product with fewer calories per container and per serving. Analysis of covariance models with Tukey-Kramer tests were used. Covariates included general label use, age, sex, level of education, and race/ethnicity. Single-serving and dual-column formats performed better and scored higher on most outcome measures. For products that contain 2 servings but are customarily consumed at a single eating occasion, using a single-serving or dual-column labeling approach may help consumers make healthier food choices. Published by Elsevier Inc.

  18. Efficacy of two different doses of rabbit anti-T-lymphocyte globulin to prevent graft-versus-host disease in children with haematological malignancies transplanted from an unrelated donor: a multicentre, randomised, open-label, phase 3 trial

    OpenAIRE

    Locatelli, Franco; Bernardo, Maria Ester; Bertaina, Alice; Rognoni, Carla; Comoli, Patrizia; Rovelli, Attilio; Pession, Andrea; Fagioli, Franca; Favre, Claudio; Lanino, Edoardo; Giorgiani, Giovanna; Merli, Pietro; Pagliara, Daria; Prete, Arcangelo; Zecca, Marco

    2017-01-01

    Background Although rabbit anti-T-lymphocyte globulin (ATLG) is largely used for the prevention of immunemediated complications in patients given allogeneic haemopoietic stem-cell transplantation (HSCT) from an unrelated donor, the optimum dose of this drug in children is still undefined. We aimed to test whether a higher dose of ATLG was superior to a lower dose for prevention of grade II–IV acute graft-versus-host disease (GVHD). Methods We conducted a multicentre, randomised, open-label, p...

  19. Single dose systemic acetaminophen to improve patient reported quality of recovery after ambulatory segmental mastectomy: A prospective, randomized, double-blinded, placebo controlled, clinical trial.

    Science.gov (United States)

    De Oliveira, Gildasio S; Rodes, Meghan E; Bialek, Jane; Kendall, Mark C; McCarthy, Robert J

    2017-11-15

    Few systemic drug interventions are efficacious to improve patient reported quality of recovery after ambulatory surgery. We aimed to evaluate whether a single dose systemic acetaminophen improve quality of recovery in female patients undergoing ambulatory breast surgery. We hypothesized that patients receiving a single dose systemic acetaminophen at the end of the surgical procedure would have a better global quality of postsurgical recovery compared to the ones receiving saline. The study was a prospective randomized double blinded, placebo controlled, clinical trial. Healthy female subjects were randomized to receive 1 g single dose systemic acetaminophen at the end of the surgery or the same volume of saline. The primary outcome was the Quality of Recovery 40 (QOR-40) questionnaire at 24 hours after surgery. Other data collected included opioid consumption and pain scores. Data were analyzed using group t tests and the Wilcoxon exact test. The association between opioid consumption and quality of recovery was evaluated using Spearman rho. P quality of recovery, P = .007. A single dose of systemic acetaminophen improves patient reported quality of recovery after ambulatory breast surgery. The use of systemic acetaminophen is an efficacious strategy to improve patient perceived quality of postsurgical recovery and analgesic outcomes after hospital discharge for ambulatory breast surgery. © 2017 Wiley Periodicals, Inc.

  20. Efficacy and Safety of Single and Double Doses of Ivermectin versus 7-Day High Dose Albendazole for Chronic Strongyloidiasis

    Science.gov (United States)

    Suputtamongkol, Yupin; Premasathian, Nalinee; Bhumimuang, Kid; Waywa, Duangdao; Nilganuwong, Surasak; Karuphong, Ekkapun; Anekthananon, Thanomsak; Wanachiwanawin, Darawan; Silpasakorn, Saowaluk

    2011-01-01

    Background Strongyloidiasis, caused by an intestinal helminth Strongyloides stercoralis, is common throughout the tropics. It remains an important health problem due to autoinfection, which may result in hyperinfection and disseminated infection in immunosuppressed patients, especially patients receiving chemotherapy or corticosteroid treatment. Ivermectin and albendazole are effective against strongyloidiasis. However, the efficacy and the most effective dosing regimen are to be determined. Methods A prospective, randomized, open study was conducted in which a 7-day course of oral albendazole 800 mg daily was compared with a single dose (200 microgram/kilogram body weight), or double doses, given 2 weeks apart, of ivermectin in Thai patients with chronic strongyloidiasis. Patients were followed-up with 2 weeks after initiation of treatment, then 1 month, 3 months, 6 months, 9 months, and 1 year after treatment. Combination of direct microscopic examination of fecal smear, formol-ether concentration method, and modified Koga agar plate culture were used to detect strongyloides larvae in two consecutive fecal samples in each follow-up visit. The primary endpoint was clearance of strongyloides larvae from feces after treatment and at one year follow-up. Results Ninety patients were included in the analysis (30, 31 and 29 patients in albendazole, single dose, and double doses ivermectin group, respectively). All except one patient in this study had at least one concomitant disease. Diabetes mellitus, systemic lupus erythrematosus, nephrotic syndrome, hematologic malignancy, solid tumor and human immunodeficiency virus infection were common concomitant diseases in these patients. The median (range) duration of follow-up were 19 (2–76) weeks in albendazole group, 39 (2–74) weeks in single dose ivermectin group, and 26 (2–74) weeks in double doses ivermectin group. Parasitological cure rate were 63.3%, 96.8% and 93.1% in albendazole, single dose oral ivermectin

  1. Methylphenidate, cognition, and epilepsy: A 1-month open-label trial.

    Science.gov (United States)

    Adams, Jesse; Alipio-Jocson, Valerie; Inoyama, Katherine; Bartlett, Victoria; Sandhu, Saira; Oso, Jemima; Barry, John J; Loring, David W; Meador, Kimford J

    2017-12-01

    Cognitive difficulties are common in epilepsy. Beyond reducing seizures and adjusting antiepileptic medications, no well-validated treatment exists in adults. Methylphenidate is used effectively in children with epilepsy and attention-deficit/hyperactivity disorder, but its effects in adults have not been systematically evaluated. We hypothesized that methylphenidate can safely improve cognition in adults with epilepsy. We detail here the open-label follow-up to a double-blind, placebo-controlled, single-dose study. Thirty epilepsy patients entered a 1-month open-label methylphenidate trial after a double-blind phase. Doses were titrated according to clinical practice and patient tolerance, ranging 20-40 mg/day. Primary measures included: Conners' Continuous Performance Test (CPT), Symbol-Digit Modalities Test (SDMT), and Medical College of Georgia Memory Test (MCG). Secondary measures were: Beck Depression Inventory, 2nd Edition (BDI-II), Beck Anxiety Inventory, Apathy Evaluation Scale (AES), Stimulant Side-Effect Checklist, Adverse Events Profile, Quality of Life in Epilepsy-89 (QOLIE-89), and seizure frequency. Fourteen healthy, nonmedicated controls were tested concurrently. Twenty-eight participants with epilepsy (13 men/15 women) completed the trial. Withdrawals occurred due to anxiety (n = 1) and fatigue (n = 1). Mean age was 36.4 years (range = 20-60). Epilepsy types were: focal (n = 21), generalized (n = 6), or unclassified (n = 1). Mean epilepsy duration was 12.3 years. Mean baseline seizure frequency was 2.8/month. There were significant improvements on methylphenidate for SDMT, MCG, CPT (the ability to discriminate between targets and nontargets [d'] hits, hit reaction time standard deviation, omissions, and commissions), and QOLIE subscales (energy/fatigue, attention/concentration, memory, and language; paired t tests; p ≤ 0.002). BDI-II and additional subscales also improved, at a lower level of statistical significance. Effect

  2. Immunogenicity and safety of purified chick-embryo cell rabies vaccine under Zagreb 2-1-1 or 5-dose Essen regimen in Chinese children 6 to 17 years old and adults over 50 years: A randomized open-label study

    Science.gov (United States)

    Li, RongCheng; Li, YanPing; Wen, ShuQing; Wen, HuiChun; Nong, Yi; Mo, Zhaojun; Xie, Fang; Pellegrini, Michele

    2015-01-01

    The aim of this Phase IIIb, open-label, randomized study was to demonstrate the non-inferiority of immune responses and to assess the safety of a purified chick-embryo cell rabies vaccine (PCECV) in healthy Chinese children (6 to 17 years) and older adults (≥51 years) following 2 alternative intramuscular (IM) simulated post-exposure prophylaxis (PEP) regimens: 4-dose Zagreb or 5-dose Essen regimen. Serum samples were collected prior to vaccination on Days 1 and 15 and on day 43 to assess immune response by rabies virus neutralizing antibody (RVNA) concentrations. Solicited adverse events (AEs) were recorded for up to 7 days following each vaccine dose, and unsolicited AEs throughout the entire study period. PCECV vaccination induced a strong immune response at Day 15, and the non-inferiority in immune response of the Zagreb vs. the Essen regimen was demonstrated in children and older adults. At Day 15,100% of children (N = 224), and 99% of subjects ≥51 years of age (N = 376) developed adequate RVNA concentrations (≥0.5 IU/mL); at Day 43 all subjects achieved RVNA concentrations ≥0.5 IU/mL, for both PEP regimens. The well-known tolerability and safety profile of the PCECV was again observed in this study following either Zagreb or Essen regimens. Rabies PEP vaccination with PCECV following a Zagreb regimen induced immune responses non-inferior to those of the Essen regimen, and had a similar safety and tolerability profile to the Essen regimen in Chinese children, adolescents, and adults over 51 years. ClinicalTrials.gov identifier: NCT01680016. PMID:25692350

  3. Pharmacokinetic interaction between udenafil and dapoxetine: a randomized, open-labeled crossover study in healthy male volunteers

    Directory of Open Access Journals (Sweden)

    Kim YH

    2015-02-01

    Full Text Available Yo Han Kim,1 Hee Youn Choi,1 Shi Hyang Lee,1 Hae Sun Jeon,1 Hyeong-Seok Lim,1 Mi Young Bahng,2 Kyun-Seop Bae1 1Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, College of Medicine, University of Ulsan, 2Clinical Development Department, Dong-A ST Co, Ltd, Seoul, Republic of Korea Background: “Udenafil” is a phosphodiesterase-5 inhibitor indicated for erectile dysfunction. “Dapoxetine” is a serotonin transport inhibitor indicated for premature ejaculation. The aim of the study reported here was to investigate the pharmacokinetic drug interaction between udenafil and dapoxetine in healthy male subjects. Methods: An open-label, three-treatment, six-sequence, three-period crossover study was performed in healthy male subjects. In varying sequences, each subjects received single oral doses of udenafil 200 mg, dapoxetine 60 mg, and both treatments. The periods were separated by a washout period of 7 days. Serial blood samples were collected up to 48 hours after dosing. The plasma concentrations of udenafil and dapoxetine were determined using a validated liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters were obtained by non-compartmental analysis. Tolerability was assessed throughout the study. Results: Twenty-three healthy subjects completed the study. The geometric mean ratios of the area under the plasma concentration–time curve from time 0 to last measurable time point and measured peak plasma concentration for udenafil were 0.923 (90% confidence interval [CI]: 0.863–0.987 and 0.864 (90% CI: 0.789–0.947, respectively. The geometric mean ratios of the area under the plasma concentration–time curve from time 0 to last measurable time point and measured peak plasma concentration for dapoxetine were 1.125 (90% CI: 1.044–1.213 and 0.837 (90% CI: 0.758–0.925, respectively. There were no serious adverse events reported, and none of the subjects dropped out due to adverse events

  4. Pilot Randomized Controlled Trial of Titrated Subcutaneous Ketamine in Older Patients with Treatment-Resistant Depression.

    Science.gov (United States)

    George, Duncan; Gálvez, Verònica; Martin, Donel; Kumar, Divya; Leyden, John; Hadzi-Pavlovic, Dusan; Harper, Simon; Brodaty, Henry; Glue, Paul; Taylor, Rohan; Mitchell, Philip B; Loo, Colleen K

    2017-11-01

    To assess the efficacy and safety of subcutaneous ketamine for geriatric treatment-resistant depression. Secondary aims were to examine if repeated treatments were safe and more effective in inducing or prolonging remission than a single treatment. In this double-blind, controlled, multiple-crossover study with a 6-month follow-up (randomized controlled trial [RCT] phase), 16 participants (≥60 years) with treatment-resistant depression who relapsed after remission or did not remit in the RCT were administered an open-label phase. Up to five subcutaneous doses of ketamine (0.1, 0.2, 0.3, 0.4, and 0.5 mg/kg) were administered in separate sessions (≥1 week apart), with one active control (midazolam) randomly inserted (RCT phase). Twelve ketamine treatments were given in the open-label phase. Mood, hemodynamic, and psychotomimetic outcomes were assessed by blinded raters. Remitters in each phase were followed for 6 months. Seven of 14 RCT-phase completers remitted with ketamine treatment. Five remitted at doses below 0.5 mg/kg. Doses ≥ 0.2 mg/kg were significantly more effective than midazolam. Ketamine was well tolerated. Repeated treatments resulted in higher likelihood of remission or longer time to relapse. Results provide preliminary evidence for the efficacy and safety of ketamine in treating elderly depressed. Dose titration is recommended for optimizing antidepressant and safety outcomes on an individual basis. Subcutaneous injection is a practical method for giving ketamine. Repeated treatments may improve remission rates (clinicaltrials.gov; NCT01441505). Copyright © 2017 American Association for Geriatric Psychiatry. All rights reserved.

  5. Efficacy, safety and tolerability of escitalopram in doses up to 50 mg in Major Depressive Disorder (MDD: an open-label, pilot study

    Directory of Open Access Journals (Sweden)

    Crawford Gordon M

    2011-03-01

    Full Text Available Abstract Background Escitalopram is licensed for use at doses up to 20 mg but is used clinically at higher doses. There is limited published data at higher doses and none in the treatment of Major Depressive Disorder (MDD. Methods This open-label, pilot study was designed to investigate the efficacy, safety and tolerability of escitalopram in doses up to 50 mg in MDD. It was conducted in 60 primary care patients with MDD who had not responded to adequate treatment with citalopram. Patients were treated with escalating doses of escitalopram up to 50 mg for up to 32 weeks until they achieved remission (Montgomery-Asberg Depression Rating Scale [MADRS] ≤8 or failed to tolerate the dose. Results Forty-two patients (70% completed the study. Twenty-one patients (35% achieved remission with 8 of the 21 patients (38% needing the 50 mg dose to achieve remission. Median time to remission was 24 weeks and median dose in remission was 30 mg. No significant safety issues were identified although tolerability appeared to decline above a dose of 40 mg with 26% of patients unable to tolerate 50 mg. Twelve (20% patients had adverse events leading to discontinuation. The most common adverse events were headache (35%, nausea, diarrhoea and nasopharyngitis (all 25%. Minor mean weight gain was found during the study, which did not appear to be dose-related. Half of the patients who completed the study chose to continue treatment with escitalopram rather than taper down the dose at 32 weeks. Conclusions Dose escalation with escitalopram above 20 mg may have a useful role in the management of patients with MDD, although further studies are needed to confirm this finding. Trial Registration ClinicalTrials.gov: NCT00785434

  6. Isavuconazole treatment for mucormycosis: a single-arm open-label trial and case-control analysis.

    Science.gov (United States)

    Marty, Francisco M; Ostrosky-Zeichner, Luis; Cornely, Oliver A; Mullane, Kathleen M; Perfect, John R; Thompson, George R; Alangaden, George J; Brown, Janice M; Fredricks, David N; Heinz, Werner J; Herbrecht, Raoul; Klimko, Nikolai; Klyasova, Galina; Maertens, Johan A; Melinkeri, Sameer R; Oren, Ilana; Pappas, Peter G; Ráčil, Zdeněk; Rahav, Galia; Santos, Rodrigo; Schwartz, Stefan; Vehreschild, J Janne; Young, Jo-Anne H; Chetchotisakd, Ploenchan; Jaruratanasirikul, Sutep; Kanj, Souha S; Engelhardt, Marc; Kaufhold, Achim; Ito, Masanori; Lee, Misun; Sasse, Carolyn; Maher, Rochelle M; Zeiher, Bernhardt; Vehreschild, Maria J G T

    2016-07-01

    Mucormycosis is an uncommon invasive fungal disease with high mortality and few treatment options. Isavuconazole is a triazole active in vitro and in animal models against moulds of the order Mucorales. We assessed the efficacy and safety of isavuconazole for treatment of mucormycosis and compared its efficacy with amphotericin B in a matched case-control analysis. In a single-arm open-label trial (VITAL study), adult patients (≥18 years) with invasive fungal disease caused by rare fungi, including mucormycosis, were recruited from 34 centres worldwide. Patients were given isavuconazole 200 mg (as its intravenous or oral water-soluble prodrug, isavuconazonium sulfate) three times daily for six doses, followed by 200 mg/day until invasive fungal disease resolution, failure, or for 180 days or more. The primary endpoint was independent data review committee-determined overall response-ie, complete or partial response (treatment success) or stable or progressive disease (treatment failure)-according to prespecified criteria. Mucormycosis cases treated with isavuconazole as primary treatment were matched with controls from the FungiScope Registry, recruited from 17 centres worldwide, who received primary amphotericin B-based treatment, and were analysed for day-42 all-cause mortality. VITAL is registered with ClinicalTrials.gov, number NCT00634049. FungiScope is registered with ClinicalTrials.gov, number NCT01731353. Within the VITAL study, from April 22, 2008, to June 21, 2013, 37 patients with mucormycosis received isavuconazole for a median of 84 days (IQR 19-179, range 2-882). By day 42, four patients (11%) had a partial response, 16 (43%) had stable invasive fungal disease, one (3%) had invasive fungal disease progression, three (8%) had missing assessments, and 13 (35%) had died. 35 patients (95%) had adverse events (28 [76%] serious). Day-42 crude all-cause mortality in seven (33%) of 21 primary-treatment isavuconazole cases was similar to 13 (39%) of 33

  7. Bioequivalence of fixed-dose combination Myrin®-P Forte and reference drugs in loose combination.

    Science.gov (United States)

    Wang, H F; Wang, R; O'Gorman, M; Crownover, P; Naqvi, A; Jafri, I

    2013-12-01

    Myrin®-P Forte is a fixed-dose combination (FDC) tablet containing rifampicin (RMP, 150 mg), isoniazid (INH, 75 mg), ethambutol (EMB) hydrochloride (275 mg) and pyrazinamide (PZA, 400 mg) developed for the treatment of tuberculosis (TB). This study was conducted at a single centre--the Pfizer Clinical Research Unit in Singapore. To demonstrate the bioequivalence of each drug component of the Myrin-P Forte FDC and the individual product in loose combination. In a randomized, open-label, single-dose, two-way, crossover study, subjects received single doses of Myrin-P Forte or four individual products under fasting conditions in a crossover fashion with at least 7 days washout between doses. The primary measures for comparison were peak plasma concentration (C(max)) and the area under plasma concentration-time curve (AUC). Of 36 subjects enrolled, 35 completed the study. The adjusted geometric mean ratios and 90% confidence intervals for C(max) and AUC values were completely contained within bioequivalence limits (80%, 125%) for all four drugs in both formulations. Both treatments were generally well tolerated in the study. The Myrin-P Forte FDC tablet formulation is bioequivalent to the four single-drug references for RMP, INH, EMB hydrochloride and PZA at equivalent doses.

  8. A multicenter, prospective, single arm, open label, observational study of sTMS for migraine prevention (ESPOUSE Study).

    Science.gov (United States)

    Starling, Amaal J; Tepper, Stewart J; Marmura, Michael J; Shamim, Ejaz A; Robbins, Matthew S; Hindiyeh, Nada; Charles, Andrew C; Goadsby, Peter J; Lipton, Richard B; Silberstein, Stephen D; Gelfand, Amy A; Chiacchierini, Richard P; Dodick, David W

    2018-05-01

    Objective To evaluate the efficacy and tolerability of single pulse transcranial magnetic stimulation (sTMS) for the preventive treatment of migraine. Background sTMS was originally developed for the acute treatment of migraine with aura. Open label experience has suggested a preventive benefit. The objective of this trial was to evaluate the efficacy and tolerability of sTMS for migraine prevention. Methods The eNeura SpringTMS Post-Market Observational U.S. Study of Migraine (ESPOUSE) Study was a multicenter, prospective, open label, observational study. From December 2014 to March 2016, patients with migraine (n = 263) were consented to complete a 1-month baseline headache diary followed by 3 months of treatment. The treatment protocol consisted of preventive (four pulses twice daily) and acute (three pulses repeated up to three times for each attack) treatment. Patients reported daily headache status, medication use, and device use with a monthly headache diary. The primary endpoint, mean reduction of headache days compared to baseline, was measured over the 28-day period during weeks 9 to 12. The primary endpoint was compared to a statistically-derived placebo estimate (performance goal). Secondary endpoints included: 50% responder rate, acute headache medication consumption, HIT-6, and mean reduction in total headache days from baseline of any intensity. Results Of a total of 263 consented subjects, 229 completed a baseline diary, and 220 were found to be eligible based on the number of headache days. The device was assigned to 217 subjects (Safety Data Set) and 132 were included in the intention to treat Full Analysis Set. For the primary endpoint, there was a -2.75 ± 0.40 mean reduction of headache days from baseline (9.06 days) compared to the performance goal (-0.63 days) ( p < 0.0001). The 50% responder rate of 46% (95% CI 37%, 56%) was also significantly higher ( p < 0.0001) than the performance goal (20%). There was a reduction of -2

  9. Human absorbed dose calculations for 123I labeled phenyl pentadecanoic acid

    International Nuclear Information System (INIS)

    Kulkarni, P.V.; Clark, G.; Corbett, J.R.; Willerson, J.T.; Parkey, R.W.

    1986-01-01

    I-123 labeled fatty acids have been proposed for studying myocardial metabolism by scintigraphic methods. With the availability of clean I-123 and the advent of single photon emission tomography, I-123 labeled fatty acids would be well suited to study regional myocardial viability or metabolism in humans. The authors have studied I-125 and I-123 labeled iodophenyl pentadecanoic acid (IPPA) in rats and dogs. Clinical studies are in progress with I-123 (IPPA). They have studied the pharmacokinetics of this tracer in male Sprague-Dawley rats at 0.25, 0.5, 1, 3, 6, and 24 hours postinjection. The cumulated doses, due to both pure I-123 and a version contaminated with 1.4% I-125, in various organs and the total body in humans are estimated. The average dose to organs for humans injected with I-123 IPPA with pure I-123 and contaminated I-123 respectively, are (rads to organ per mCi injected): heart wall (0.0507, 0.0514), liver (0.0792, 0.0875), kidneys (0.0479, 0.0561), thyroid (0.0517, 0.0638), ovaries (0.0427, 0.0561), testes (0.0307, 0.0309), total body (0.0386, 0.0392). 12 references, 9 figures, 5 tables

  10. High-Dose Versus Low-Dose Pitavastatin in Japanese Patients With Stable Coronary Artery Disease (REAL-CAD): A Randomized Superiority Trial.

    Science.gov (United States)

    Taguchi, Isao; Iimuro, Satoshi; Iwata, Hiroshi; Takashima, Hiroaki; Abe, Mitsuru; Amiya, Eisuke; Ogawa, Takanori; Ozaki, Yukio; Sakuma, Ichiro; Nakagawa, Yoshihisa; Hibi, Kiyoshi; Hiro, Takafumi; Fukumoto, Yoshihiro; Hokimoto, Seiji; Miyauchi, Katsumi; Yamazaki, Tsutomu; Ito, Hiroshi; Otsuji, Yutaka; Kimura, Kazuo; Takahashi, Jun; Hirayama, Atsushi; Yokoi, Hiroyoshi; Kitagawa, Kazuo; Urabe, Takao; Okada, Yasushi; Terayama, Yasuo; Toyoda, Kazunori; Nagao, Takehiko; Matsumoto, Masayasu; Ohashi, Yasuo; Kaneko, Tetsuji; Fujita, Retsu; Ohtsu, Hiroshi; Ogawa, Hisao; Daida, Hiroyuki; Shimokawa, Hiroaki; Saito, Yasushi; Kimura, Takeshi; Inoue, Teruo; Matsuzaki, Masunori; Nagai, Ryozo

    2018-05-08

    Current guidelines call for high-intensity statin therapy in patients with cardiovascular disease on the basis of several previous "more versus less statins" trials. However, no clear evidence for more versus less statins has been established in an Asian population. In this prospective, multicenter, randomized, open-label, blinded end point study, 13 054 Japanese patients with stable coronary artery disease who achieved low-density lipoprotein cholesterol (LDL-C) fashion to high-dose (pitavastatin 4 mg/d; n=6526) or low-dose (pitavastatin 1 mg/d; n=6528) statin therapy. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergency hospitalization. The secondary composite end point was a composite of the primary end point and clinically indicated coronary revascularization excluding target-lesion revascularization at sites of prior percutaneous coronary intervention. The mean age of the study population was 68 years, and 83% were male. The mean LDL-C level before enrollment was 93 mg/dL with 91% of patients taking statins. The baseline LDL-C level after the run-in period on pitavastatin 1 mg/d was 87.7 and 88.1 mg/dL in the high-dose and low-dose groups, respectively. During the entire course of follow-up, LDL-C in the high-dose group was lower by 14.7 mg/dL than in the low-dose group ( P Japanese patients with stable coronary artery disease. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01042730. © 2018 The Authors.

  11. Efficacy of praziquantel against Schistosoma mekongi and Opisthorchis viverrini: a randomized, single-blinded dose-comparison trial.

    Directory of Open Access Journals (Sweden)

    Leonore Lovis

    Full Text Available BACKGROUND: Schistosomiasis and opisthorchiasis are of public health importance in Southeast Asia. Praziquantel (PZQ is the drug of choice for morbidity control but few dose comparisons have been made. METHODOLOGY: Ninety-three schoolchildren were enrolled in an area of Lao PDR where Schistosoma mekongi and Opisthorchis viverrini coexist for a PZQ dose-comparison trial. Prevalence and intensity of infections were determined by a rigorous diagnostic effort (3 stool specimens, each examined with triplicate Kato-Katz before and 28-30 days after treatment. Ninety children with full baseline data were randomized to receive PZQ: the 40 mg/kg standard single dose (n = 45 or a 75 mg/kg total dose (50 mg/kg+25 mg/kg, 4 hours apart; n = 45. Adverse events were assessed at 3 and 24 hours posttreatment. PRINCIPAL FINDINGS: Baseline infection prevalence of S. mekongi and O. viverrini were 87.8% and 98.9%, respectively. S. mekongi cure rates were 75.0% (95% confidence interval (CI: 56.6-88.5% and 80.8% (95% CI: 60.6-93.4% for 40 mg/kg and 75 mg/kg PZQ, respectively (P = 0.60. O. viverrini cure rates were significantly different at 71.4% (95% CI: 53.4-84.4% and 96.6% (95% CI: not defined, respectively (P = 0.009. Egg reduction rates (ERRs against O. viverrini were very high for both doses (>99%, but slightly lower for S. mekongi at 40 mg/kg (96.4% vs. 98.1% and not influenced by increasing diagnostic effort. O. viverrini cure rates would have been overestimated and no statistical difference between doses found if efficacy was based on a minimum sampling effort (single Kato-Katz before and after treatment. Adverse events were common (96%, mainly mild with no significant differences between the two treatment groups. CONCLUSIONS/SIGNIFICANCE: Cure rate from the 75 mg/kg PZQ dose was more efficacious than 40 mg/kg against O. viverrini but not against S. mekongi infections, while ERRs were similar for both doses. TRIAL REGISTRATION: Controlled

  12. Use of ChAd3-EBO-Z Ebola virus vaccine in Malian and US adults, and boosting of Malian adults with MVA-BN-Filo: a phase 1, single-blind, randomised trial, a phase 1b, open-label and double-blind, dose-escalation trial, and a nested, randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Tapia, Milagritos D; Sow, Samba O; Lyke, Kirsten E; Haidara, Fadima Cheick; Diallo, Fatoumata; Doumbia, Moussa; Traore, Awa; Coulibaly, Flanon; Kodio, Mamoudou; Onwuchekwa, Uma; Sztein, Marcelo B; Wahid, Rezwanul; Campbell, James D; Kieny, Marie-Paule; Moorthy, Vasee; Imoukhuede, Egeruan B; Rampling, Tommy; Roman, Francois; De Ryck, Iris; Bellamy, Abbie R; Dally, Len; Mbaya, Olivier Tshiani; Ploquin, Aurélie; Zhou, Yan; Stanley, Daphne A; Bailer, Robert; Koup, Richard A; Roederer, Mario; Ledgerwood, Julie; Hill, Adrian V S; Ballou, W Ripley; Sullivan, Nancy; Graham, Barney; Levine, Myron M

    2016-01-01

    The 2014 west African Zaire Ebola virus epidemic prompted worldwide partners to accelerate clinical development of replication-defective chimpanzee adenovirus 3 vector vaccine expressing Zaire Ebola virus glycoprotein (ChAd3-EBO-Z). We aimed to investigate the safety, tolerability, and immunogenicity of ChAd3-EBO-Z in Malian and US adults, and assess the effect of boosting of Malians with modified vaccinia Ankara expressing Zaire Ebola virus glycoprotein and other filovirus antigens (MVA-BN-Filo). In the phase 1, single-blind, randomised trial of ChAd3-EBO-Z in the USA, we recruited adults aged 18-65 years from the University of Maryland medical community and the Baltimore community. In the phase 1b, open-label and double-blind, dose-escalation trial of ChAd3-EBO-Z in Mali, we recruited adults 18-50 years of age from six hospitals and health centres in Bamako (Mali), some of whom were also eligible for a nested, randomised, double-blind, placebo-controlled trial of MVA-BN-Filo. For randomised segments of the Malian trial and for the US trial, we randomly allocated participants (1:1; block size of six [Malian] or four [US]; ARB produced computer-generated randomisation lists; clinical staff did randomisation) to different single doses of intramuscular immunisation with ChAd3-EBO-Z: Malians received 1 × 10(10) viral particle units (pu), 2·5 × 10(10) pu, 5 × 10(10) pu, or 1 × 10(11) pu; US participants received 1 × 10(10) pu or 1 × 10(11) pu. We randomly allocated Malians in the nested trial (1:1) to receive a single dose of 2 × 10(8) plaque-forming units of MVA-BN-Filo or saline placebo. In the double-blind segments of the Malian trial, investigators, clinical staff, participants, and immunology laboratory staff were masked, but the study pharmacist (MK), vaccine administrator, and study statistician (ARB) were unmasked. In the US trial, investigators were not masked, but participants were. Analyses were per protocol. The primary outcome was safety, measured

  13. An open-label, flexible-dose study of paliperidone extended-release in Chinese patients with first-onset psychosis

    Directory of Open Access Journals (Sweden)

    Si TM

    2015-01-01

    Full Text Available TianMei Si,1 QingRong Tan,2 KeRang Zhang,3 Yang Wang,4 Qing Rui4 1Peking University Institute of Mental health, Key Laboratory of Mental Health, Ministry of Health (Peking University, Beijing, 2Fourth Military Medical University, First Hospital, Xi’an, 3Shanxi Medical University, First Hospital, Shanxi, 4Janssen Research and Development, Beijing, People’s Republic of China Background: Antipsychotic medications facilitate the improvement of psychotic symptoms in patients with first-episode psychosis. Paliperidone extended-release (pali-ER, an atypical anti­psychotic, was assessed for efficacy and safety in Chinese patients with first-episode psychosis. Methods: In this 8-week, open-label, single-arm, multicenter study, patients with first-episode psychosis (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria and a Positive and Negative Syndrome Scale (PANSS total score ≥70 were treated with flexible-dose pali-ER tablets (3–12 mg/day. The primary efficacy endpoint was the percentage of patients with an increase of ≥8 points in Personal and Social Performance (PSP score from baseline to day 56 (8 weeks. Secondary endpoints included reduction in PANSS total score, improvement in Clinical Global Impression-Severity score, PSP score, Subjective Well-being under Neuroleptics Scale score, and relationship between duration of untreated psychosis and PANSS or PSP. Incidences of treatment-emergent adverse events were used to evaluate safety.Results: Overall, 283 of 294 patients (96% achieved a ≥8-point increase in PSP (primary endpoint, analysis set. For the secondary efficacy endpoints, 284/306 patients (93% had a ≥30% reduction in PANSS total score; 266/306 patients (87% achieved a ≤3 Clinical Global Impression-Severity scale score, and 218/294 patients (74% had a PSP score ≥71. The Subjective Well-being under Neuroleptics Scale score was improved from a baseline mean of 72.7 to 94.7 at endpoint. There was a

  14. A long-term, open-label safety study of single-entity hydrocodone bitartrate extended release for the treatment of moderate to severe chronic pain

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    Nalamachu S

    2014-11-01

    Full Text Available Srinivas Nalamachu,1,2 Richard L Rauck,3 Martin E Hale,4 Orlando G Florete Jr,5 Cynthia Y Robinson,6 Stephen J Farr,6 1International Clinical Research Institute, Overland Park, KS, USA; 2Kansas University Medical Center, Kansas City, KS, USA; 3Carolinas Pain Institute, Center for Clinical Research, Wake Forest University School of Medicine, Winston-Salem, NC, USA; 4Gold Coast Research, LLC, Weston, FL, USA; 5Institute of Pain Management, Jacksonville, FL, USA; 6Zogenix, Inc., Emeryville, CA, USA Objective: To evaluate the long-term safety, tolerability, and effectiveness of single-entity extended-release hydrocodone in opioid-experienced subjects with moderate to severe chronic pain not receiving adequate pain relief or experiencing intolerable side effects from their current opioid. Methods: This multicenter, open-label study started with a conversion/titration phase (≤6 weeks where subjects (n=638 were converted to individualized doses (range 20–300 mg of extended-release hydrocodone dosed every 12 hours, followed by a 48-week maintenance phase (n=424. The primary objective (safety and tolerability and the secondary objective (long-term efficacy as measured by change in average pain score; 0= no pain, 10= worst imaginable pain were monitored throughout the study. Results: Subjects were treated for a range of chronic pain etiologies, including osteoarthritis, low back pain, and neuropathic and musculoskeletal conditions. The mean hydrocodone equivalent dose at screening was 68.9±62.2 mg/day and increased to 139.5±81.7 mg/day at the start of the maintenance phase. Unlimited dose adjustments were permitted at the investigator's discretion during the maintenance phase, reflecting typical clinical practice. No unexpected safety issues were reported. Common adverse events during the conversion/titration and maintenance phases, respectively, were constipation (11.3% and 12.5%, nausea (10.7% and 9.9%, vomiting (4.1% and 9.7%, and somnolence (7

  15. Radioautography of rat incisor dentin as a continuous record of the incorporation of a single dose of 3H-labeled proline and tyrosine

    International Nuclear Information System (INIS)

    Josephsen, K.; Warshawsky, H.

    1982-01-01

    After injection of labeled precursors such as 3 H-proline or 3 H-tyrosine into rats, the incisor dentin contains a continuous and stable record of precursor incorporation into labeled proteins. This record was visualized and quantitated with radioautography in order to evaluate the quantitative changes in enamel where newly secreted proteins randomize with older proteins and both are eventually lost. Up to 4 hours after injection, the pulse-dose was incorporated as a highly labeled band of predentin. The band was entirely within calcified dentin at 2 days and was further removed from new predentin by 4 and 8 days. Dentin which formed proximal to the heavily labeled band contained an amount of radioactivity reflecting the level of labeled precursor available at that time. A standardizing factor for experimental error was obtained by quantitating the reaction in the heavily labeled band, and a post-pulse incorporation factor was determined from the amount of radioactivity added per day as weakly labeled dentin. The variation within the heavily labeled band was assumed to reflect experimental error. The number of grains in the bands were averaged from 4 hours to 8 days to give the standardizing factor. This was multiplied by the ratio of enamel to dentin counts in the same section to obtain a corrected enamel count. With proline it amounted to 5% increase per day from 1 to 4 days and 2.5% per day from 4 to 8 days after injection. In addition, with 3 H-proline the incorporation into predentin increased from 30 minutes to 4 hours. With tyrosine, the counts increased from 30 minutes to 1 hour, but decreased by nearly one third from 1 to 4 hours. This was interpreted as a loss of short-lived matrix proteins including procollagen peptides produced during conversion from procollagen to tropocollagen in the predentin

  16. The effects of orally administered Beta-glucan on innate immune responses in humans, a randomized open-label intervention pilot-study.

    Directory of Open Access Journals (Sweden)

    Jenneke Leentjens

    Full Text Available To prevent or combat infection, increasing the effectiveness of the immune response is highly desirable, especially in case of compromised immune system function. However, immunostimulatory therapies are scarce, expensive, and often have unwanted side-effects. β-glucans have been shown to exert immunostimulatory effects in vitro and in vivo in experimental animal models. Oral β-glucan is inexpensive and well-tolerated, and therefore may represent a promising immunostimulatory compound for human use.We performed a randomized open-label intervention pilot-study in 15 healthy male volunteers. Subjects were randomized to either the β -glucan (n = 10 or the control group (n = 5. Subjects in the β-glucan group ingested β-glucan 1000 mg once daily for 7 days. Blood was sampled at various time-points to determine β-glucan serum levels, perform ex vivo stimulation of leukocytes, and analyze microbicidal activity.β-glucan was barely detectable in serum of volunteers at all time-points. Furthermore, neither cytokine production nor microbicidal activity of leukocytes were affected by orally administered β-glucan.The present study does not support the use of oral β-glucan to enhance innate immune responses in humans.ClinicalTrials.gov NCT01727895.

  17. The MANDELA study: A multicenter, randomized, open-label, parallel group trial to refine the use of everolimus after heart transplantation.

    Science.gov (United States)

    Deuse, Tobias; Bara, Christoph; Barten, Markus J; Hirt, Stephan W; Doesch, Andreas O; Knosalla, Christoph; Grinninger, Carola; Stypmann, Jörg; Garbade, Jens; Wimmer, Peter; May, Christoph; Porstner, Martina; Schulz, Uwe

    2015-11-01

    In recent years a series of trials has sought to define the optimal protocol for everolimus-based immunosuppression in heart transplantation, with the goal of minimizing exposure to calcineurin inhibitors (CNIs) and harnessing the non-immunosuppressive benefits of everolimus. Randomized studies have demonstrated that immunosuppressive potency can be maintained in heart transplant patients receiving everolimus despite marked CNI reduction, although very early CNI withdrawal may be inadvisable. A potential renal advantage has been shown for everolimus, but the optimal time for conversion and the adequate reduction in CNI exposure remain to be defined. Other reasons for use of everolimus include a substantial reduction in the risk of cytomegalovirus infection, and evidence for inhibition of cardiac allograft vasculopathy, a major cause of graft loss. The ongoing MANDELA study is a 12-month multicenter, randomized, open-label, parallel-group study in which efficacy, renal function and safety are compared in approximately 200 heart transplant patients. Patients receive CNI therapy, steroids and everolimus or mycophenolic acid during months 3 to 6 post-transplant, and are then randomized at month 6 post-transplant (i) to convert to CNI-free immunosuppression with everolimus and mycophenolic acid or (ii) to continue reduced-exposure CNI, with concomitant everolimus. Patients are then followed to month 18 post-transplant The rationale and expectations for the trial and its methodology are described herein. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Safety and efficacy of pregabalin in adolescents with fibromyalgia: a randomized, double-blind, placebo-controlled trial and a 6-month open-label extension study.

    Science.gov (United States)

    Arnold, Lesley M; Schikler, Kenneth N; Bateman, Lucinda; Khan, Tahira; Pauer, Lynne; Bhadra-Brown, Pritha; Clair, Andrew; Chew, Marci L; Scavone, Joseph

    2016-07-30

    Fibromyalgia (FM) is a common pain condition characterized by widespread musculoskeletal pain and tenderness. Pregabalin is an approved treatment for adults in the United States, but there are no approved treatments for adolescents with FM. This was a 15-week, randomized, double-blind, placebo-controlled study and 6-month open-label safety trial of flexible-dose pregabalin (75-450 mg/day) for the treatment of adolescents (12-17 years) with FM. Primary outcome was change in mean pain score at endpoint (scored from 0-10, with 24-h recall). Secondary outcomes included global assessments and measures of pain, sleep, and FM impact. A total of 107 subjects were randomized to treatment (54 pregabalin, 53 placebo) and 80 completed the study (44 pregabalin, 36 placebo). Improvement in mean pain score at endpoint with pregabalin versus placebo was not statistically significant, treatment difference (95 % CI), -0.66 (-1.51, 0.18), P = 0.121. There were significant improvements with pregabalin versus placebo in secondary outcomes of change in pain score by week (P recall), treatment difference (95 % CI), -0.87 (-1.68, -0.05), P = 0.037; and patient global impression of change, 53.1 % versus 29.5 % very much or much improved (P = 0.013). Trends toward improvement with pregabalin in other secondary outcomes measuring pain, sleep, and FM impact were not significant. Safety was consistent with the known profile of pregabalin in adults with FM. Pregabalin did not significantly improve the mean pain score in adolescents with FM. There were significant improvements in secondary outcomes measuring pain and impression of change. NCT01020474 ; NCT01020526 .

  19. Comparison of oral psoralen-UV-A with a portable tanning unit at home vs hospital-administered bath psoralen-UV-A in patients with chronic hand eczema - An open-label randomized controlled trial of efficacy

    NARCIS (Netherlands)

    van Coevorden, AM; Kamphof, WG; van Sonderen, E; Bruynzeel, DP; Coenraads, PJ

    2004-01-01

    Objective: To study whether oral psoralen-UV-A (PUVA) with a portable tanning unit at home is as effective as hospital-administered bath PUVA in patients with chronic hand eczema. Design: Open-label randomized controlled trial, with a 10-week treatment period and an 8-week follow-up period. Setting:

  20. Open-label comparative clinical study of chlorproguanil-dapsone fixed dose combination (Lapdap alone or with three different doses of artesunate for uncomplicated Plasmodium falciparum malaria.

    Directory of Open Access Journals (Sweden)

    Daniel G Wootton

    2008-03-01

    Full Text Available The objective of this study was to determine the appropriate dose of artesunate for use in a fixed dose combination therapy with chlorproguanil-dapsone (CPG-DDS for the treatment of uncomplicated falciparum malaria.Open-label clinical trial comparing CPG-DDS alone or with artesunate 4, 2, or 1 mg/kg at medical centers in Blantyre, Malawi and Farafenni, The Gambia. The trial was conducted between June 2002 and February 2005, including 116 adults (median age 27 years and 107 children (median age 38 months with acute uncomplicated Plasmodium falciparum malaria. Subjects were randomized into 4 groups to receive CPG-DDS alone or plus 4, 2 or 1 mg/kg of artesunate once daily for 3 days. Assessments took place on Days 0-3 in hospital and follow-up on Days 7 and 14 as out-patients. Efficacy was evaluated in the Day 3 per-protocol (PP population using mean time to reduce baseline parasitemia by 90% (PC90. A number of secondary outcomes were also included. Appropriate artesunate dose was determined using a pre-defined decision matrix based on primary and secondary outcomes. Treatment emergent adverse events were recorded from clinical assessments and blood parameters. Safety was evaluated in the intent to treat (ITT population.In the Day 3 PP population for the adult group (N = 85, mean time to PC90 was 19.1 h in the CPG-DDS group, significantly longer than for the +artesunate 1 mg/kg (12.5 h; treatment difference -6.6 h [95%CI -11.8, -1.5], 2 mg/kg (10.7 h; -8.4 h [95%CI -13.6, -3.2] and 4 mg/kg (10.3 h; -8.7 h [95%CI -14.1, -3.2] groups. For children in the Day 3 PP population (N = 92, mean time to PC90 was 21.1 h in the CPG-DDS group, similar to the +artesunate 1 mg/kg group (17.7 h; -3.3 h [95%CI -8.6, 2.0], though the +artesunate 2 mg/kg and 4 mg/kg groups had significantly shorter mean times to PC90 versus CPG-DDS; 14.4 h (treatment difference -6.4 h [95%CI -11.7, -1.0] and 12.8 h (-7.4 h [95%CI -12.9, -1.8], respectively. An analysis of mean time

  1. Tolerance of the human spinal cord to single dose radiosurgery

    International Nuclear Information System (INIS)

    Ryu, S.; Zhu, G.; Yin, F.-F.; Ajlouni, M.; Kim, J.H.

    2003-01-01

    Tolerance of the spinal cord to the single dose of radiation is not well defined. Although there are cases of human spinal cord tolerance from re-irradiation to the same cord level, the information about the tolerance of human spinal cord to single large dose of radiosurgery is not available. We carried out spinal radiosurgery to treat spinal metastasis and studied the single dose tolerance of the human spinal cord in an ongoing dose escalation paradigm. A total of 39 patients with 48 lesions of spinal metastasis were treated with single dose radiosurgery at Henry Ford Hospital. The radiosurgery dose was escalated from 8 Gy to 16 Gy at 2 Gy increment. The radiation dose was prescribed to periphery of the spinal tumor. The radiation dose to the spinal cord was estimated by computerized dosimetry. The median follow-up time was 10 months (range 6-18 months) from the radiosurgery. The endpoint of the study was to demonstrate the efficacy of the spinal radiosurgery and to determine the tolerance of human spinal cord to single dose radiosurgery. The dose to the spinal cord was generally less than 50 % of the prescribed radiation dose. The volume of the spinal cord that received higher than this dose was less than 20 % of the anterior portion of the spinal cord. Maximum single dose of 8 Gy was delivered to the anterior 20 % of the spinal cord in this dose escalation study. The dose volume histogram will be presented. There was no acute or subacute radiation toxicity detected clinically and radiologically during the maximum follow-up of 20 months. Further dose escalation is in progress. The single tolerance dose of the human spinal cord appears to be at least 8 Gy when it was given to the 20 % of the cord volume, although the duration of follow up is not long enough to detect severe late cord toxicity. This study offers a valuable radiobiological basis of the normal spinal cord tolerance, and opens spinal radiosurgery as a safe treatment for spinal metastasis

  2. A randomized, double-blind, placebo-controlled trial of paracetamol and ketoprofren lysine salt for pain control in children with pharyngotonsillitis cared by family pediatricians

    Directory of Open Access Journals (Sweden)

    Della Casa Alberighi Ornella

    2011-09-01

    Full Text Available Abstract Background To evaluate the analgesic effect and tolerability of paracetamol syrup compared to placebo and ketoprofen lysine salt in children with pharyngotonsillitis cared by family pediatricians. Methods A double-blind, randomized, placebo-controlled trial of a 12 mg/kg single dose of paracetamol paralleled by open-label ketoprofren lysine salt sachet 40 mg. Six to 12 years old children with diagnosis of pharyngo-tonsillitis and a Children's Sore Throat Pain (CSTP Thermometer score > 120 mm were enrolled. Primary endpoint was the Sum of Pain Intensity Differences (SPID of the CSTP Intensity scale by the child. Results 97 children were equally randomized to paracetamol, placebo or ketoprofen. Paracetamol was significantly more effective than placebo in the SPID of children and parents (P Conclusions A single oral dose of paracetamol or ketoprofen lysine salt are safe and effective analgesic treatments for children with sore throat in daily pediatric ambulatory care.

  3. The Lack of Effect of Food on the Pharmacokinetics of ZX008 (Fenfluramine Oral Solution): Results of a Single-dose, Two-period Crossover Study.

    Science.gov (United States)

    Gammaitoni, Arnold; Smith, Steven; Boyd, Brooks

    2018-06-22

    Fenfluramine is being developed as a low-dose adjunctive treatment for seizures in patients with Dravet syndrome and other epileptic encephalopathies, including Lennox-Gastaut syndrome. Most patients with Dravet syndrome receive multiple antiepileptic drugs, making it challenging for caregivers to track correct administration times. The present Phase I study was conducted to determine the effect of food on the pharmacokinetic properties of fenfluramine. Healthy nonsmoking subjects aged 18 to 50years were enrolled in an open-label, crossover, Phase I pharmacokinetic and safety profile study and received 2 single 0.8-mg/kg doses of ZX008 (fenfluramine hydrochloride oral solution), 1 after a 10-hour overnight fast and the other 30 minutes after the start of consumption of a high-fat breakfast, in a randomly assigned order. A washout period of at least 9days separated the 2 treatment periods. Venous blood samples were taken before each dose and periodically for 72hours after each dose for determination of concentrations of fenfluramine and its active metabolite norfenfluramine. Plasma pharmacokinetic parameters were estimated for each subject by noncompartmental analysis. In the 13 subjects completing both treatment periods, food had no effect on the rate or extent of absorption and bioavailability of fenfluramine as assessed by fed vs fasted adjusted geometric mean observed plasma C max (59.1vs 56.7 ng/mL; NS) and AUC 0-∞ (1640vs 1600 ng · h/mL; NS). Additionally, there was no impact of food on systemic exposure of norfenfluramine. Seven subjects reported at least 1 treatment-emergent adverse event; all treatment-emergent adverse events were mild in severity. The bioequivalence and tolerability of single 0.8-mg/kg oral doses of ZX008 in the fed and fasted states support ZX008 administration without regard to meals. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  4. A phase 1, open-label, randomized study to compare the immunogenicity and safety of different administration routes and doses of virosomal influenza vaccine in elderly.

    Science.gov (United States)

    Levin, Yotam; Kochba, Efrat; Shukarev, Georgi; Rusch, Sarah; Herrera-Taracena, Guillermo; van Damme, Pierre

    2016-10-17

    Influenza remains a significant problem in elderly despite widespread vaccination coverage. This randomized, phase-I study in elderly compared different strategies of improving vaccine immunogenicity. A total of 370 healthy participants (⩾65years) were randomized equally 1:1:1:1:1:1 to six influenza vaccine treatments (approximately 60-63 participants per treatment arm) at day 1 that consisted of three investigational virosomal vaccine formulations at doses of 7.5, 15, and 45μg HA antigen/strain administered intradermally (ID) by MicronJet600™ microneedle device (NanoPass Technologies) or intramuscularly (IM), and three comparator registered seasonal vaccines; Inflexal V™ (Janssen) and MF59 adjuvanted Fluad™ (Novartis) administered IM and Intanza™ (Sanofi Pasteur) administered ID via Soluvia™ prefilled microinjection system (BD). Serological evaluations were performed at days 22 and 90 and safety followed-up for 6months. Intradermal delivery of virosomal vaccine using MicronJet600™ resulted in significantly higher immunogenicity than the equivalent dose of virosomal Inflexal V™ administered intramuscularly across most of the parameters and strains, as well as in some of the readouts and strains as compared with the 45μg dose of virosomal vaccine formulation. Of 370 participants, 300 (81.1%) reported ⩾1 adverse event (AE); more participants reported solicited local AEs (72.2%) than solicited systemic AEs (12.2%). Intradermal delivery significantly improved influenza vaccine immunogenicity compared with intramuscular delivery. Triple dose (45μg) virosomal vaccine did not demonstrate any benefit on vaccine's immunogenicity over 15μg commercial presentation. All treatments were generally safe and well-tolerated. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. Pharmacokinetics and Safety of Intravenous Murepavadin Infusion in Healthy Adult Subjects Administered Single and Multiple Ascending Doses.

    Science.gov (United States)

    Wach, Achim; Dembowsky, Klaus; Dale, Glenn E

    2018-04-01

    Murepavadin is the first in class of the outer membrane protein-targeting antibiotics (OMPTA) and a pathogen-specific peptidomimetic antibacterial with a novel, nonlytic mechanism of action targeting Pseudomonas aeruginosa Murepavadin is being developed for the treatment of hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP). The pharmacokinetics (PK) and safety of single and multiple doses of murepavadin were investigated in healthy male subjects. Part A of the study was a double-blind, randomized, placebo-controlled, single-ascending-dose investigation in 10 sequential cohorts where each cohort comprised 6 healthy male subjects; 4 subjects were randomized to murepavadin, and 2 subjects were randomized to placebo. Part B was a double-blind, randomized, placebo-controlled, multiple-ascending-dose investigation in 3 sequential cohorts. After a single dose of murepavadin, the geometric mean half-life (2.52 to 5.30 h), the total clearance (80.1 to 114 ml/h/kg), and the volume of distribution (415 to 724 ml/kg) were consistent across dose levels. The pharmacokinetics of the dosing regimens evaluated were dose proportional and linear. Murepavadin was well tolerated, adverse events were transient and generally mild, and no dose-limiting toxicity was identified. Copyright © 2018 American Society for Microbiology.

  6. Single-dose intra-articular bupivacaine plus morphine versus bupivacaine alone after arthroscopic knee surgery: a meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Yang, Ye; Zeng, Chao; Wei, Jie; Li, Hui; Yang, Tuo; Deng, Zhen-Han; Li, Yu-Sheng; Yang, Tu-Bao; Lei, Guang-Hua

    2017-03-01

    The purpose of this meta-analysis was to compare the efficacy and safety of single-dose intra-articular bupivacaine plus morphine versus bupivacaine alone for pain management following arthroscopic knee surgery. A comprehensive literature search was conducted to identify randomized controlled trials that used single-dose intra-articular bupivacaine plus morphine and bupivacaine alone for post-operative pain, using MEDLINE (1966-2014), Cochrane Library and EMBASE databases. The weighted mean difference (WMD), relative risk (RR) and their corresponding 95 % confidence intervals (CIs) were calculated using RevMan statistical software. A total of twenty-nine trials (n = 1167) were included. The post-operative visual analog scale (VAS) pain score of the bupivacaine plus morphine group compared with the bupivacaine alone group was significantly lower (WMD -1.15, 95 % CI -1.67 to -0.63, p bupivacaine plus morphine was shown to be significantly better than bupivacaine alone at relieving post-operative pain after arthroscopic knee surgery without increasing the short-term side effects. Routine use of single-dose intra-articular bupivacaine plus morphine is an effective way for pain management after arthroscopic knee surgery. II.

  7. Bioequivalence of a single 400-mg dose of imatinib 100-mg oral tablets and a 400-mg tablet in healthy adult Korean volunteers.

    Science.gov (United States)

    Lee, Hae Won; Seong, Sook Jin; Park, Sung Min; Lee, Joomi; Gwon, Mi-Ri; Kim, Hyun-Ju; Lim, Sung Mook; Lim, Mi-Sun; Kim, Woomi; Yang, Dong Heon; Yoon, Young-Ran

    2015-06-01

    Imatinib mesylate (IM) is a selective tyrosine kinase inhibitor for the treatment of chronic myeloid leukemia and gastrointestinal stromal tumors. A new once-daily 400-mg film-coated tablet of imatinib has been developed by a pharmaceutical company in Korea. The present study was designed to assess and compare the PK parameters, bioavailability, and bioequivalence of the new imatinib 400-mg formulation (test) versus the conventional 100-mg formulation (reference) administered as a single 400-mg dose in healthy adult male volunteers. This randomized, open-label, single-dose, two-way crossover study was conducted in healthy Korean male volunteers. Eligible subjects were randomly assigned in a 1 : 1 ratio to receive 400 mg of the test (one 400-mg tablet) or reference (four 100-mg tablets) formulation, followed by a 2-week washout period and administration of the alternate formulation. Serial blood samples were collected at 0 (predose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 48, and 72 hours after administration. Plasma imatinib concentrations were determined using liquid chromatography coupled with tandem mass spectrometry. The formulations were to be considered bioequivalent if the 90% confidence intervals (CIs) of the adjusted geometric mean ratios for Cmax, AUC(0-t), and AUC(0-∞)ž were within the predetermined range of 0.80 - 1.25. In total, 35 subjects completed the study. No serious adverse event was reported during the study. The 90% CIs of the adjusted geometric mean ratios of the test formulation to the reference formulation for C(max), AUC(0-t) and AUC(0-∞)ž of imatinib were all within the bioequivalence criteria range of 0.8 - 1.25. The test formulation of imatinib met the Korean regulatory requirements for bioequivalence. Both imatinib formulations were well-tolerated in all subjects.

  8. Failure Rate of Single Dose Methotrexate in Managment of Ectopic Pregnancy

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    Feras Sendy

    2015-01-01

    Full Text Available Background. One of the treatment modalities for ectopic pregnancy is methotrexate. The purpose of this study is to identify the failure rate of methotrexate in treating patients with ectopic pregnancy as well as the risk factors leading to treatment failure. Methods. A retrospective chart review of 225 patients who received methotrexate as a primary management option for ectopic pregnancy. Failure of single dose of methotrexate was defined as drop of BHCG level less than or equal to 14% in the seventh day after administration of methotrexate. Results. 225 patients had methotrexate. Most of the patients (151 (67% received methotrexate based on the following formula: f 50 mg X body surface area. Single dose of methotrexate was successful in 72% (162/225 of the patients. 28% (63/225 were labeled as failure of single dose of methotrexate because of suboptimal drop in BhCG. 63% (40/63 of failure received a second dose of methotrexate, and 37% (23/63 underwent surgical treatment. Among patient who received initial dose of methotrexate, 71% had moderate or severe pain, and 58% had ectopic mass size of more than 4 cm on ultrasound. Conclusion. Liberal use of medical treatment of ectopic pregnancy results in 71% success rate.

  9. Failure rate of single dose methotrexate in managment of ectopic pregnancy.

    Science.gov (United States)

    Sendy, Feras; AlShehri, Eman; AlAjmi, Amani; Bamanie, Elham; Appani, Surekha; Shams, Taghreed

    2015-01-01

    Background. One of the treatment modalities for ectopic pregnancy is methotrexate. The purpose of this study is to identify the failure rate of methotrexate in treating patients with ectopic pregnancy as well as the risk factors leading to treatment failure. Methods. A retrospective chart review of 225 patients who received methotrexate as a primary management option for ectopic pregnancy. Failure of single dose of methotrexate was defined as drop of BHCG level less than or equal to 14% in the seventh day after administration of methotrexate. Results. 225 patients had methotrexate. Most of the patients (151 (67%)) received methotrexate based on the following formula: f 50 mg X body surface area. Single dose of methotrexate was successful in 72% (162/225) of the patients. 28% (63/225) were labeled as failure of single dose of methotrexate because of suboptimal drop in BhCG. 63% (40/63) of failure received a second dose of methotrexate, and 37% (23/63) underwent surgical treatment. Among patient who received initial dose of methotrexate, 71% had moderate or severe pain, and 58% had ectopic mass size of more than 4 cm on ultrasound. Conclusion. Liberal use of medical treatment of ectopic pregnancy results in 71% success rate.

  10. A Measurement and Analysis of Buildup Region Dose for Open Field Photon Beams (Cobalt-60 through 24 MV)

    International Nuclear Information System (INIS)

    McCullough, Edwin C.

    2015-01-01

    The central axis depth dose in the build-up region (surface to d_m_a_x) of single open field photon beams (cobalt-60 through 24 MV) has been measured utilizing parallel plate and extrapolation chamber methodology. These data were used to derive, for a prescription dose of 100 cGy, values of surface dose, the maximum value of dose along the central axis (D_m_a_x) and the depth (nearest the surface) at which 90% of the prescription dose occurs (d_9_0). For both single and parallel opposed pair (POP) open field configurations, data are presented at field sizes of 5 × 5, 15 × 15 and 25 × 25 cm"2 for prescription depths of 10, 15 and 20 cm (midplane for POP). For the treatment machines, field sizes, and prescription depths studied, it is possible to conclude that: for single open field irradiation, surface dose values (as a percentage of the prescription dose) can be either low (<10%) or comparable to the prescription dose itself; for POP open fields, surface dose values are relatively independent of photon energy and midplane depth, and range between 30% and 70% of prescription dose, being principally dependent on field size; the depth of the initial 90 cGy point for a prescription dose of 100 cGy, d_9_0, was larger for POP fields. For either single or POP open field treatments, d_9_0 was always less than 22 mm, while for 6 MV or less, values of d_9_0 were less than 4 mm; D_m_a_x values can be very large (e.g., above 300 cGy) for certain treatment situations and are reduced significantly for POP treatments; for open field POP treatments, the percent reduction in D_m_a_x with each increment in beam energy above 10 MV is reduced over that seen at 10 MV or less and, possibly, this further reduction may be clinically insignificant; for open field POP treatments, changes in surface dose, d_9_0 and D_m_a_x with beam energy above 10 MV do not suggest, with regard to these specific build-up curve parameters, any obvious advantage for treatment with beam energies greater

  11. A single dose of erythropoietin reduces perioperative transfusions in cardiac surgery: results of a prospective single-blind randomized controlled trial.

    Science.gov (United States)

    Weltert, Luca; Rondinelli, Beatrice; Bello, Ricardo; Falco, Mauro; Bellisario, Alessandro; Maselli, Daniele; Turani, Franco; De Paulis, Ruggero; Pierelli, Luca

    2015-07-01

    We conducted a prospective single-blind randomized study to assess whether a single 80,000 IU dose of human recombinant erythropoietin (HRE), given just 2 days before cardiac surgery, could be effective in reducing perioperative allogeneic red blood cell transfusion (aRBCt). Six-hundred patients presenting with preoperative hemoglobin (Hb) level of not more than 14.5 g/dL were randomly assigned to either HRE or control. The primary endpoint was the incidence of perioperative aRBCt. The secondary endpoints were mortality and the incidence of adverse events in the first 45 days after surgery, Hb level on Postoperative Day 4, and number of units of RBC transfusions in the first 4 days after surgery. A total of 17% (HRE) versus 39% (control) required transfusion (relative risk, 0.436; pHRE (0%) and control (3.5%) among the patients with baseline Hb of 13.0 g/dL or more, which included the nonanemic fraction of the study population. The mean (range) Hb level on Postoperative Day 4 was 10.2 (9.9-10.6) g/dL (HRE) versus 8.7 (8.5-9.2) g/dL (control; pHRE (pHRE) versus 3.33% (control). The 45-day adverse event rate was 4.33% (HRE) versus 5.67% (control; both p=NS). In anemic patients (HbHRE administered 2 days before cardiac surgery is effective in reducing the incidence of aRBCt without increasing adverse events. © 2015 AABB.

  12. Evaluation of the Pharmacokinetics of Single- and Multiple-dose Buprenorphine Buccal Film in Healthy Volunteers.

    Science.gov (United States)

    Bai, Stephen A; Xiang, Qinfang; Finn, Andrew

    2016-02-01

    Buprenorphine, a partial μ-receptor agonist, is approved for the management of moderate to severe pain, but it has low oral bioavailability. Two open-label studies were performed to determine the pharmacokinetic profile of buprenorphine from buccal film formulations of buprenorphine. Both studies enrolled healthy volunteers, aged 18 to 55 years, who received concurrent oral naltrexone to reduce adverse events (AEs); subjects with a history or evidence of substance abuse or current use of any product affecting cytochrome P450 3A4 activity were excluded. The first study (n = 25) was a 5-period crossover trial with 4 single doses (75 and 300 and 300 and 1200 μg) of 2 formulations (F14 and F24) of buccal buprenorphine (BBUP) and a 300-μg intravenous dose of buprenorphine with a 7-day washout between periods. In the second study, each subject (n = 10) received 6 doses of 4 BBUP strengths (60, 120, 180, and 240 μg BID) in a dose-escalation design. Plasma concentrations of buprenorphine and norbuprenorphine were assayed, and pharmacokinetics were summarized with descriptive statistics and analyzed by using a linear mixed effects model (single-dose study). AEs were recorded. In the single-dose study, the 2 formulations exhibited comparable bioavailability of 46% to 51% that was independent of dose, with a single buprenorphine peak concentration from each BBUP dose occurring at 2.5 to 3 hours. The mean buprenorphine Cmax across the doses ranged from 0.17 ng/mL for the 75-µg dose to 1.43 ng/mL for the 1200-µg dose. AUC0-∞, AUC0-last, and Cmax were proportional to the dose of BBUP administered. Cmax of norbuprenorphine after BBUP administration was approximately one tenth that of buprenorphine Cmax. In the multiple-dose study, steady state was reached within 3 days of BID dosing. There was a linear increase in exposure across the dose range from 60 to 240 μg BID. Treatment-emergent AEs in both studies were consistent with those reported with opiate administration to

  13. Single-dose radiotherapy for painful bone metastases

    International Nuclear Information System (INIS)

    Kal, H.B.

    1999-01-01

    Background: External beam radiotherapy is frequently applied for palliative treatment of painful bone lesions with a variety of fractionation schemes. There is a continuous interest to administer only 1 or a few dose fractions for inducing pain relief. Methods: A review of the literature was made with the aim to determine whether a treatment can be deduced that is simple and effective. The linear-quadratic (L-Q) concept was applied to compare reported therapy schemes which each other for the iso-effect pain relief. Results: Single-dose and fractionated radiotherapy resulted in partial or complete pain relief in about 80% of the patients. Complete responses have been observed in about 43% of the patients. For patients responding to treatment, the duration of pain relief is at least 3 to 4 months with reported duration of up to 1 year or even longer. Conclusion: Based on this review of literature data concerning randomized trials a treatment with a single dose of 8 Gy is effective for inducing pain relief. (orig.) [de

  14. Tofacitinib, an oral Janus kinase inhibitor, for the treatment of chronic plaque psoriasis: Long-term efficacy and safety results from 2 randomized phase-III studies and 1 open-label long-term extension study.

    Science.gov (United States)

    Papp, Kim A; Krueger, James G; Feldman, Steven R; Langley, Richard G; Thaci, Diamant; Torii, Hideshi; Tyring, Stephen; Wolk, Robert; Gardner, Annie; Mebus, Charles; Tan, Huaming; Luo, Yingchun; Gupta, Pankaj; Mallbris, Lotus; Tatulych, Svitlana

    2016-05-01

    Tofacitinib is an oral Janus kinase inhibitor being investigated for psoriasis. We sought to report longer-term tofacitinib efficacy and safety in patients with moderate to severe psoriasis. Data from 2 identical phase-III studies, Oral-treatment Psoriasis Trial Pivotal 1 and 2, were pooled with data from these patients in an ongoing open-label long-term extension study. Patients (n = 1861) were randomized 2:2:1 to tofacitinib 5 mg, 10 mg, or placebo twice daily (BID). At week 16, placebo patients were rerandomized to tofacitinib. Pivotal study participants could enroll into the long-term extension where they received tofacitinib at 10 mg BID for 3 months, after which dosing could be 5 or 10 mg BID. At week 28, the proportions of patients randomized to tofacitinib 5 and 10 mg BID achieving 75% or greater reduction in Psoriasis Area and Severity Index score from baseline were 55.6% and 68.8%, and achieving Physician Global Assessment of clear or almost clear were 54.7% and 65.9%. Efficacy was maintained in most patients through 24 months. Serious adverse events and discontinuations because of adverse events were reported in less than 11% of patients over 33 months of tofacitinib exposure. There was no dose comparison beyond week 52. Oral tofacitinib demonstrated sustained efficacy in patients with psoriasis through 2 years, with 10 mg BID providing greater efficacy than 5 mg BID. No unexpected safety findings were observed. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  15. An open-label, multicenter evaluation of the long-term safety and efficacy of risperidone in adolescents with schizophrenia

    Directory of Open Access Journals (Sweden)

    Pandina Gahan

    2012-06-01

    Full Text Available Abstract Background Data on the long-term efficacy, safety, and tolerability of risperidone in adolescents with schizophrenia are limited. The objective of this study was to evaluate the efficacy and safety of maintenance risperidone treatment in adolescents with schizophrenia. Methods This open-label study of adolescents aged 13 to 17 years with schizophrenia was a single extension study of two short-term double-blind risperidone studies and also enrolled subjects directly in open-label risperidone treatment. The risperidone dose was flexible and ranged from 2 to 6 mg/day. Most subjects enrolled for 6 months; a subset enrolled for 12 months. Assessment tools included the Positive and Negative Syndrome Scale total and factor scores, Clinical Global Impressions, Children’s Global Assessment Scale, adverse event (AE monitoring, vital signs, laboratory testing, and extrapyramidal symptom rating scales. Results A total of 390 subjects were enrolled; 48 subjects had received placebo in a previous double-blind study; 292 subjects had received risperidone as part of their participation in one of two previous controlled studies; and 50 subjects were enrolled directly for this study. A total of 279 subjects enrolled for 6 months of treatment, and 111 subjects enrolled for 12 months of treatment. Overall, 264 (67.7% subjects completed this study: 209 of the 279 subjects (75% in the 6-month group and 55 of the 111 subjects (50% in the 12-month group. The median mode dose was 3.8 mg/day. At 6 months, all three groups experienced improvement from open-label baseline in symptoms of schizophrenia as well as general assessments of global functioning. Improvements were generally maintained for the duration of treatment. The most common AEs (≥10% of subjects were somnolence, headache, weight increase, hypertonia, insomnia, tremor, and psychosis. Potentially prolactin-related AEs (PPAEs were reported by 36 (9% subjects. The AE profile in this study was

  16. Efficacy of Single-dose and 2-dose Intravenous Administration of Ramosetron in Preventing Postoperative Nausea and Vomiting After Laparoscopic Gynecologic Operation: A Randomized, Double-blind, Placebo-controlled, Phase 2 Trial.

    Science.gov (United States)

    Lee, Banghyun; Kim, Kidong; Suh, Dong Hoon; Shin, Hyun-Jung; No, Jae Hong; Lee, Jung Ryeol; Jee, Byung Chul; Hwang, Jung Won; Do, Sang Hwan; Kim, Yong Beom

    2017-06-01

    This randomized trial investigated whether a 2-dose administration of intravenous ramosetron (5-hydroxytryptamine type 3 receptor antagonist) is more effective than a single-dose administration in preventing postoperative nausea and vomiting (PONV) in 89 patients who were scheduled to undergo laparoscopic operation for benign gynecologic diseases and to receive intravenous patient-controlled analgesia for relief of postoperative pain. After assignment at a ratio of 1:1, intravenous ramosetron (0.3 mg) was initially administered at the end of skin closure in all patients. Thereafter, ramosetron (0.3 mg) and placebo were administered to the study and control groups, respectively, at 4 hours after the operation. The baseline and operative characteristics were similar between the groups. The incidence of PONV during the 24-hour period after operation which was assessed as the primary endpoint did not differ between the groups. No serious adverse events occurred in either group. A 2-dose administration of intravenous ramosetron may not be superior to a single-dose administration in preventing PONV in patients undergoing laparoscopic operation for benign gynecologic diseases.

  17. Dataset for Phase I randomized clinical trial for safety and tolerability of GET 73 in single and repeated ascending doses including preliminary pharmacokinetic parameters.

    Science.gov (United States)

    Haass-Koffler, Carolina L; Goodyear, Kimberly; Long, Victoria M; Tran, Harrison H; Loche, Antonella; Cacciaglia, Roberto; Swift, Robert M; Leggio, Lorenzo

    2017-12-01

    The data in this article outline the methods used for the administration of GET 73 in the first time-in-human manuscript entitled "Phase I randomized clinical trial for the safety, tolerability and preliminary pharmacokinetics of the mGluR5 negative allosteric modulator GET 73 following single and repeated doses in healthy male volunteers" (Haass-Koffler et al., 2017) [1]. Data sets are provided in two different manners. The first series of tables provided includes procedural information about the experiments conducted. The next series of tables provided includes Pharmacokinetic (PK) parameters for GET 73 and its main metabolite MET 2. This set of data is comprised by two experiments: Experiment 1 references a single ascending dose administration of GET 73 and Experiment 2 references a repeated ascending dose administration of GET 73.

  18. The steady-state pharmacokinetics of nevirapine during once daily and twice daily dosing in HIV-1-infected individuals

    NARCIS (Netherlands)

    van Heeswijk, R. P.; Veldkamp, A. I.; Mulder, J. W.; Meenhorst, P. L.; Wit, F. W.; Lange, J. M.; Danner, S. A.; Foudraine, N. A.; Kwakkelstein, M. O.; Reiss, P.; Beijnen, J. H.; Hoetelmans, R. M.

    2000-01-01

    OBJECTIVE: To investigate and to compare the steady-state plasma pharmacokinetics of nevirapine in a dosing regimen of 400 mg once daily versus 200 mg twice daily in HIV-1-infected individuals. DESIGN: Open-label, randomized, cross-over study. METHODS: Twenty HIV-1-infected individuals who already

  19. Effect of Facial Cosmetic Acupuncture on Facial Elasticity: An Open-Label, Single-Arm Pilot Study

    Directory of Open Access Journals (Sweden)

    Younghee Yun

    2013-01-01

    Full Text Available Background. The use of acupuncture for cosmetic purposes has gained popularity worldwide. Facial cosmetic acupuncture (FCA is applied to the head, face, and neck. However, little evidence supports the efficacy and safety of FCA. We hypothesized that FCA affects facial elasticity by restoring resting mimetic muscle tone through the insertion of needles into the muscles of the head, face, and neck. Methods. This open-label, single-arm pilot study was implemented at Kyung Hee University Hospital at Gangdong from August through September 2011. Participants were women aged 40 to 59 years with a Glogau photoaging scale III. Participants received five treatment sessions over three weeks. Participants were measured before and after FCA. The primary outcome was the Moire topography criteria. The secondary outcome was a patient-oriented self-assessment scale of facial elasticity. Results. Among 50 women screened, 28 were eligible and 27 completed the five FCA treatment sessions. A significant improvement after FCA treatment was evident according to mean change in Moire topography criteria (from 1.70 ± 0.724 to 2.26 ± 1.059, P<0.0001. The most common adverse event was mild bruising at the needle site. Conclusions. In this pilot study, FCA showed promising results as a therapy for facial elasticity. However, further large-scale trials with a controlled design and objective measurements are needed.

  20. The behavior of rats irradiated with a sublethal single dose of γ-rays on the region of head in open field test

    International Nuclear Information System (INIS)

    Smajda, B.; Kiskova, J.; Kereskenyiova, E.

    2004-01-01

    The goal of this work was to establish the effects of the irradiation of head in laboratory rats on some forms of naturalistic behavior in the open field test. During a 5-day control period behavioral parameters reflecting motory and explorative activity, as well as anxiousness of animals (6 parameters in total) were followed daily in 20 male Sprague-Dowley rats in an open field test lasting 5 minutes. Fourteen animals were repeatedly tested after irradiation of head with a single dose of 10 Gy of gamma rays. The results showed statistically significant depression of motory and explorative activities during the first 3 days after irradiation in comparison with the control period. The anxiousness of animals was decreased, too. Novelty habituation was observed only in non-irradiated animals. Based on these results it is possible to presume, that the applied dose of ionizing radiation was able to influence the brain centers involved in control of naturalistic behavioral functions connected with response to new environment in rats. (authors)

  1. Safety and pharmacokinetics of single and multiple intravenous bolus doses of diclofenac sodium compared with oral diclofenac potassium 50 mg: A randomized, parallel-group, single-center study in healthy subjects.

    Science.gov (United States)

    Munjal, Sagar; Gautam, Anirudh; Okumu, Franklin; McDowell, James; Allenby, Kent

    2016-01-01

    In a randomized, parallel-group, single-center study in 42 healthy adults, the safety and pharmacokinetic parameters of an intravenous formulation of 18.75 and 37.5 mg diclofenac sodium (DFP-08) following single- and multiple-dose bolus administration were compared with diclofenac potassium 50 mg oral tablets. Mean AUC0-inf values for a 50-mg oral tablet and an 18.75-mg intravenous formulation were similar (1308.9 [393.0]) vs 1232.4 [147.6]). As measured by the AUC, DFP-08 18.75 mg and 37.5 mg demonstrated dose proportionality for extent of exposure. One subject in each of the placebo and DFP-08 18.75-mg groups and 2 subjects in the DFP-08 37.5-mg group reported adverse events that were considered by the investigator to be related to the study drug. All were mild in intensity and did not require treatment. Two subjects in the placebo group and 1 subject in the DFP-08 18.75-mg group reported grade 1 thrombophlebitis; no subjects reported higher than grade 1 thrombophlebitis after receiving a single intravenous dose. The 18.75- and 37.5-mg doses of intravenous diclofenac (single and multiple) were well tolerated for 7 days. Additional efficacy and safety studies are required to fully characterize the product. © 2015, The American College of Clinical Pharmacology.

  2. Open-label, dose-titration tolerability study of atomoxetine hydrochloride in Korean, Chinese, and Taiwanese adults with attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Takahashi, Michihiro; Goto, Taro; Takita, Yasushi; Chung, Sang-Keun; Wang, Yufeng; Gau, Susan Shur-Fen

    2014-03-01

    The primary objective of this study was to assess the overall safety and tolerability of atomoxetine in Korean, Chinese, and Taiwanese adults with attention-deficit/hyperactivity disorder (ADHD). A total of 44 patients aged ≥18 years who met the Conners' Adult ADHD Diagnostic Interview for DSM-IV diagnostic criteria for ADHD were enrolled from China, Korea, and Taiwan. In this open-label, dose-escalation study, patients received atomoxetine orally once daily over a period of eight weeks, starting at 40 mg/day (one week) up to a maximum dosage of 120 mg/day. Tolerability was evaluated by rate of discontinuation due to adverse events. Safety was assessed by recording all adverse events, laboratory tests, vital signs, and electrocardiograms. ADHD symptoms were evaluated by the Conners' Adult ADHD Rating Scale-Investigator Rated: Screening Version (CAARS-Inv:SV) for efficacy assessment. Thirty-four patients (77.3%) completed the study. Atomoxetine was well tolerated with a discontinuation rate of 2.3% (1/44) due to adverse events. The most commonly reported adverse events were nausea, dizziness, and somnolence. The mean change from baseline to endpoint in CAARS-Inv:SV total ADHD symptom score was -12.5 (P atomoxetine clinical trial in adult patients with ADHD in China, Korea, and Taiwan. Atomoxetine was well tolerated in doses of up to 120 mg/day with no unknown safety concerns. Copyright © 2012 Blackwell Publishing Asia Pty Ltd.

  3. Communicating doses of pediatric liquid medicines to parents/caregivers: a comparison of written dosing directions on prescriptions with labels applied by dispensed pharmacy.

    Science.gov (United States)

    Shah, Rita; Blustein, Leona; Kuffner, Ed; Davis, Lisa

    2014-03-01

    To identify and compare volumetric measures used by healthcare providers in communicating dosing instructions for pediatric liquid prescriptions to parents/caregivers. Dosing instructions were retrospectively reviewed for the 10 most frequently prescribed liquid medications dispensed from 4 community pharmacies for patients aged ≤ 12 years during a 3-month period. Volumetric measures on original prescriptions (ie, milliliters, teaspoons) were compared with those utilized by the pharmacist on the pharmacy label dispensed to the parent/caregiver. Of 649 prescriptions and corresponding pharmacy labels evaluated, 68% of prescriptions and 62% of pharmacy labels communicated dosing in milliliters, 24% of prescriptions and 29% of pharmacy labels communicated dosing in teaspoonfuls, 7% of prescriptions and 0% of pharmacy labels communicated dosing in other measures (ie, milligrams, cubic centimeters, "dose"), and 25% of dispensed pharmacy labels did not reflect units as written in the prescription. Volumetric measures utilized by healthcare professionals in dosing instructions for prescription pediatric oral liquid medications are not consistent. Healthcare professionals and parents/caregivers should be educated on safe dosing practices for liquid pediatric medications. Generalizability to the larger pediatric population may vary depending on pharmacy chain, location, and medications evaluated. Copyright © 2014 Mosby, Inc. All rights reserved.

  4. Effect of single-dose low-level helium-neon laser irradiation on orthodontic pain: a split-mouth single-blind placebo-controlled randomized clinical trial.

    Science.gov (United States)

    Sobouti, Farhad; Khatami, Maziar; Chiniforush, Nasim; Rakhshan, Vahid; Shariati, Mahsa

    2015-01-01

    Pain is the most common complication of orthodontic treatment. Low-level laser therapy (LLLT) has been suggested as a new analgesic treatment free of the adverse effects of analgesic medications. However, it is not studied thoroughly, and the available studies are quite controversial. Moreover, helium neon (He-Ne) laser has not been assessed before. This split-mouth placebo-controlled randomized clinical trial was performed on 16 male and 14 female orthodontic patients requiring bilateral upper canine retraction. The study was performed at a private clinic in Sari, Iran, in 2014. It was single blind: patients, orthodontist, and personnel were blinded of the allocations, but the laser operator (periodontist) was not blinded. Once canine retractor was activated, a randomly selected maxillary quarter received a single dose of He-Ne laser irradiation (632.8 nm, 10 mw, 6 j/cm(2) density). The other quarter served as the placebo side, treated by the same device but powered off. In the first, second, fourth, and seventh days, blinded patients rated their pain sensed on each side at home using visual analog scale (VAS) questionnaires. There was no harm identified during or after the study. Pain changes were analyzed using two- and one-way repeated-measures ANOVA, Bonferroni, and t-test (α = 0.01, β > 0.99). This trial was not registered. It was self-funded by the authors. Sixteen males and 11 females remained in the study (aged 12-21). Average pain scores sensed in all 4 intervals on control and laser sides were 4.06 ± 2.85 and 2.35 ± 1.77, respectively (t-test P < 0.0001). One-way ANOVA showed significant pain declines over time, in each group (P < 0.0001). Two-way ANOVA showed significant effects for LLLT (P < 0.0001) and time (P = <0.0001). Single-dose He-Ne laser therapy might reduce orthodontic pain caused by retracting maxillary canines.

  5. A new label dosimetry system based on pentacosa-diynoic acid monomer for low dose applications

    Energy Technology Data Exchange (ETDEWEB)

    Abdel-Fattah, A.A.; Abdel-Rehim, F. [National Center for Radiation Research and Technology, Atomic Energy Authority, P.O. Box 8029, Nasr City, Cairo (Egypt); Soliman, Y.S., E-mail: yasser_shabaan@hotmail.com [National Center for Radiation Research and Technology, Atomic Energy Authority, P.O. Box 8029, Nasr City, Cairo (Egypt)

    2012-01-15

    The dosimetric characteristics of {gamma}-radiation sensitive labels based on polyvinyl butyral (PVB) and a conjugated diacetylene monomer, 10,12-pentacosa-diynoic acid (PCDA) have been investigated using reflectance colorimeter. Two types of labels (colourless and yellow) based on PCDA monomer were prepared using an Automatic Film Applicator System. Upon {gamma}-ray exposure, the colourless label turns progressively blue, while the yellow colour label turns to green then to dark blue. The colour intensity of the labels is proportional to the radiation absorbed dose. The useful dose range was 15 Gy-2 kGy depending on PCDA monomer concentration. The expanded uncertainty of dose measurement of the colourless label was 6.06 (2{sigma}). - Highlights: > Using 10,12-pentacosa-diynoic acid (PCDA) in preparation of label dosimeter. > PCDA polymerises upon {gamma}-rays exposure producing a blue coloured polymer. > Useful dose range is 15 Gy to 2 kGy depending on concentration of PCDA. > Overall uncertainty of label dosimeter was 6.06 at 2{sigma}.

  6. Single- and multiple-dose pharmacokinetics of biphasic immediate-release/extended-release hydrocodone bitartrate/acetaminophen (MNK-155 compared with immediate-release hydrocodone bitartrate/ibuprofen and immediate-release tramadol HCl/acetaminophen

    Directory of Open Access Journals (Sweden)

    Devarakonda K

    2015-09-01

    Full Text Available Krishna Devarakonda,1 Kenneth Kostenbader,2 Michael J Giuliani,3 Jim L Young41Department of Clinical Pharmacology, Mallinckrodt Pharmaceuticals, 2Mallinckrodt Pharmaceuticals, 3Research and Development, Mallinckrodt Pharmaceuticals, 4Department of Clinical Affairs and Program Management, Mallinckrodt Pharmaceuticals, Hazelwood, MO, USAObjective: To characterize the single-dose and steady-state pharmacokinetics (PK of biphasic immediate-release/extended-release hydrocodone bitartrate/acetaminophen (IR/ER HB/APAP, IR HB/ibuprofen, and IR tramadol HCl/APAP.Methods: In this single-center, open-label, randomized, four-period crossover study, healthy participants received four treatments under fasted conditions: 1 a single dose of two IR/ER HB/APAP 7.5/325 mg tablets (15/650 mg total dose on day 1, followed by two tablets every 12 hours (q12h beginning on day 3; 2 a single dose of IR HB/ibuprofen 15/400 mg (divided as one 7.5/200 mg tablet at hour 0 and 6, followed by one tablet every 6 hours (q6h beginning on day 3; 3 a single dose of IR tramadol HCl/APAP 75/650 mg (divided as one 37.5/325 mg tablet at hour 0 and 6, followed by one tablet q6h beginning on day 3; and 4 a single dose of three IR/ER HB/APAP 7.5/325 mg tablets (22.5/975 mg total dose on day 1, a three-tablet initial dose at 48 hours followed by two-tablet doses q12h beginning on day 3. Hydrocodone and APAP single-dose and steady-state PK were assessed. Adverse events were monitored.Results: The PK analysis was carried out on 29 of 48 enrolled participants who completed all treatment periods. Single-dose hydrocodone exposure was similar for IR/ER HB/APAP 22.5/975 mg and IR HB/ibuprofen 15/400 mg; time to maximum observed plasma concentration was shorter and half-life was longer for IR/ER HB/APAP (22.5/975 mg and 15/650 mg vs IR HB/ibuprofen. Single-dose APAP exposure was similar for IR/ER HB/APAP 15/650 mg and IR tramadol HCl/APAP 75/650 mg. Steady-state hydrocodone and APAP exposures

  7. Randomized, controlled, assessor-blind clinical trial to assess the efficacy of single- versus repeated-dose albendazole to treat ascaris lumbricoides, trichuris trichiura, and hookworm infection.

    Science.gov (United States)

    Adegnika, Ayola A; Zinsou, Jeannot F; Issifou, Saadou; Ateba-Ngoa, Ulysse; Kassa, Roland F; Feugap, Eliane N; Honkpehedji, Yabo J; Dejon Agobe, Jean-Claude; Kenguele, Hilaire M; Massinga-Loembe, Marguerite; Agnandji, Selidji T; Mordmüller, Benjamin; Ramharter, Michael; Yazdanbakhsh, Maria; Kremsner, Peter G; Lell, Bertrand

    2014-05-01

    In many regions where soil-transmitted helminth infections are endemic, single-dose albendazole is used in mass drug administration programs to control infections. There are little data on the efficacy of the standard single-dose administration compared to that of alternative regimens. We conducted a randomized, controlled, assessor-blinded clinical trial to determine the efficacies of standard and extended albendazole treatment against soil-transmitted helminth infection in Gabon. A total of 175 children were included. Adequate cure rates and egg reduction rates above 85% were found with a single dose of albendazole for Ascaris infection, 85% (95% confidence interval [CI], 73, 96) and 93.8% (CI, 87.6, 100), respectively, while two doses were necessary for hookworm infestation (92% [CI, 78, 100] and 92% [CI, 78, 100], respectively). However, while a 3-day regimen was not sufficient to cure Trichuris (cure rate, 83% [CI, 73, 93]), this regimen reduced the number of eggs up to 90.6% (CI, 83.1, 100). The rate ratios of two- and three-dose regimens compared to a single-dose treatment were 1.7 (CI, 1.1, 2.5) and 2.1 (CI, 1.5, 2.9) for Trichuris and 1.7 (CI, 1.0, 2.9) and 1.7 (CI, 1.0, 2.9) for hookworm. Albendazole was safe and well tolerated in all regimens. A single-dose albendazole treatment considerably reduces Ascaris infection but has only a moderate effect on hookworm and Trichuris infections. The single-dose option may still be the preferred regimen because it balances efficacy, safety, and compliance during mass drug administration, keeping in mind that asymptomatic low-level helminth carriage may also have beneficial effects. (This study has been registered at ClinicalTrials.gov under registration number NCT01192802.).

  8. A randomized study comparing outcomes of stapled and hand-sutured anastomoses in patients undergoing open gastrointestinal surgery.

    Science.gov (United States)

    Chandramohan, S M; Gajbhiye, Raj Narenda; Agwarwal, Anil; Creedon, Erin; Schwiers, Michael L; Waggoner, Jason R; Tatla, Daljit

    2013-08-01

    Although stapling is an alternative to hand-suturing in gastrointestinal surgery, recent trials specifically designed to evaluate differences between the two in surgery time, anastomosis time, and return to bowel activity are lacking. This trial compared the outcomes of the two in subjects undergoing open gastrointestinal surgery. Adult subjects undergoing emergency or elective surgery requiring a single gastric, small, or large bowel anastomosis were enrolled into this open-label, prospective, randomized, interventional, parallel, multicenter, controlled trial. Randomization was assigned in a 1:1 ratio between the hand-sutured group (n = 138) and the stapled group (n = 142). Anastomosis time, surgery time, and time to bowel activity were collected and compared as primary endpoints. A total of 280 subjects were enrolled from April 2009 to September 2010. Only the time of anastomosis was significantly different between the two arms: 17.6 ± 1.90 min (stapled) and 20.6 ± 1.90 min (hand-sutured). This difference was deemed not clinically or economically meaningful. Safety outcomes and other secondary endpoints were similar between the two arms. Mechanical stapling is faster than hand-suturing for the construction of gastrointestinal anastomoses. Apart from this, stapling and hand-suturing are similar with respect to the outcomes measured in this trial.

  9. Effect of cyclic, low dose pyrimethamine treatment in patients with Late Onset Tay Sachs: an open label, extended pilot study.

    Science.gov (United States)

    Osher, Etty; Fattal-Valevski, Aviva; Sagie, Liora; Urshanski, Nataly; Sagiv, Nadav; Peleg, Leah; Lerman-Sagie, Tally; Zimran, Ari; Elstein, Deborah; Navon, Ruth; Valevski, Avi; Stern, Naftali

    2015-04-17

    Late Onset Tay- Sachs disease (LOTS) is a rare neurodegenerative lysosomal storage disease which results from mutations in the gene encoding the α subunit (HEXA) of β-hexosaminidase enzyme (HexA). At the present time, no effective treatment exists for LOTS and other neurodegenerative diseases involving the central nerve system (CNS). Pyrimethamine (PMT) was previously shown to act as a HexA chaperone in human fibroblasts in vitro carrying some (e.g., αG269S), but not all LOTS-related mutations. The present study assessed the effect of cyclic, low dose and long term pyrimethamine treatment on HexA in subjects with LOTS. In an open label trial in 4 LOTS patients, PMT was initiated at an average daily dose of ~2.7 mg and administered cyclically guided by blood lymphocyte HexA activity for a mean duration of 82.8 (±22.5; SD) weeks (~1.5 year). HexA activity rose in all subjects, with a mean peak increase of 2.24 folds (±0.52; SD) over baseline activity (range 1.87-3). The mean treatment time required to attain this peak was of 15.7 (±4.8; SD) weeks. Following increase in activity, HexA gradually declined with the continued use of PMT, which was then stopped, resulting in the return of HexA activity to baseline. A second cycle of PMT treatment was then initiated, resulting again in an increase in HexA activity. Three of the patients experienced a measurable neuropsychiatric deterioration whereas one subject remained entirely stable. Cyclic low dose of PMT can increase HexA activity in LOTS patients. However, the observed increase is repeatedly transient and not associated with discernible beneficial neurological or psychiatric effects.

  10. An open-label study of sodium oxybate in Spasmodic dysphonia.

    Science.gov (United States)

    Rumbach, Anna F; Blitzer, Andrew; Frucht, Steven J; Simonyan, Kristina

    2017-06-01

    Spasmodic dysphonia (SD) is a task-specific laryngeal dystonia that affects speech production. Co-occurring voice tremor (VT) often complicates the diagnosis and clinical management of SD. Treatment of SD and VT is largely limited to botulinum toxin injections into laryngeal musculature; other pharmacological options are not sufficiently developed. Open-label study. We conducted an open-label study in 23 SD and 22 SD/VT patients to examine the effects of sodium oxybate (Xyrem), an oral agent with therapeutic effects similar to those of alcohol in these patients. Blinded randomized analysis of voice and speech samples assessed symptom improvement before and after drug administration. Sodium oxybate significantly improved voice symptoms (P = .001) primarily by reducing the number of SD-characteristic voice breaks and severity of VT. Sodium oxybate further showed a trend for improving VT symptoms (P = .03) in a subset of patients who received successful botulinum toxin injections for the management of their SD symptoms. The drug's effects were observed approximately 30 to 40 minutes after its intake and lasted about 3.5 to 4 hours. Our study demonstrated that sodium oxybate reduced voice symptoms in 82.2% of alcohol-responsive SD patients both with and without co-occurring VT. Our findings suggest that the therapeutic mechanism of sodium oxybate in SD and SD/VT may be linked to that of alcohol, and as such, sodium oxybate might be beneficial for alcohol-responsive SD and SD/VT patients. 4 Laryngoscope, 127:1402-1407, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  11. Safety and hemostatic efficacy of fibrin pad in partial nephrectomy: Results of an open-label Phase I and a randomized, standard-of-care-controlled Phase I/II study

    Directory of Open Access Journals (Sweden)

    Nativ Ofer

    2012-11-01

    Full Text Available Abstract Background Bleeding severity, anatomic location, tissue characteristics, and visibility are common challenges encountered while managing intraoperative bleeding, and conventional hemostatic measures (suture, ligature, and cautery may sometimes be ineffective or impractical. While topical absorbable hemostats (TAH are useful hemostatic adjuvants, each TAH has associated disadvantages. Methods We evaluated the safety and hemostatic efficacy of a new advanced biologic combination product―fibrin pad―to potentially address some gaps associated with TAHs. Fibrin pad was assessed as adjunctive hemostat in open partial nephrectomy in single-center, open-label, Phase I study (N = 10, and as primary hemostat in multicenter, single-blind, randomized, standard-of-care (SOC-controlled Phase I/II study (N = 7 in Israel. It was used to control mild-to-moderate bleeding in Phase I and also spurting arterial bleeding in Phase I/II study. Phase I study assessed safety and Phase I/II study, proportion of successes at 10 min following randomization, analyzed by Fisher exact tests at 5% significance level. Results Phase I (N = 10: All patients completed the study. Hemostasis was achieved within 3–4 min (average = 3.1 min of a single application in all patients. Fibrin pad was found to be safe for human use, with no product-related adverse events reported. Phase I/II (N = 7: Hemostatic success at 10 min (primary endpoint was achieved in 3/4 patients treated with fibrin pad versus 0/3 patients treated with SOC. No clinically significant change in laboratory or coagulation parameters was recorded, except a case of post-procedural hemorrhage with fibrin pad, which was considered serious and related to the fibrin pad treatment, and required re-operation. Although Data Safety Monitoring Board authorized trial continuation, the sponsor decided against proceeding toward an indication for primary treatment of severe arterial

  12. Green tea (Camellia sinensis) for patients with knee osteoarthritis: A randomized open-label active-controlled clinical trial.

    Science.gov (United States)

    Hashempur, Mohammad Hashem; Sadrneshin, Sara; Mosavat, Seyed Hamdollah; Ashraf, Alireza

    2018-02-01

    Green tea is known as a dietary supplement and a novel functional food worldwide. Since there are increasing preclinical evidence about efficacy of green tea for treating osteoarthritis, this study has aimed at assessing its efficacy and safety for patients with knee osteoarthritis. This is a randomized open-label active-controlled clinical trial. As many as fifty adults with osteoarthritis of knee were randomly allocated to receive the green tea extract (in dosage form of tablet) plus diclofenac tablet as "intervention group"; or: diclofenac tablet alone as "control group" for a period of four weeks. Patients were assessed at the beginning of intervention, and then 4 weeks later, in terms of pain score via visual analogue scale (VAS), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire's total score in addition to its 3 sub-scores. Furthermore, they were asked about any adverse effects during intervention period. Mean differences of VAS pain, total WOMAC, and WOMAC physical function scores in green tea group showed a significant reduction, compared with the control group (P = 0.038, P = 0.006, and P = 0.004, respectively). However, No significant differences between the two groups were observed, regarding mean differences of WOMAC pain and stiffness scores of the enrolled patients (P = 0.163, and P = 0.150, respectively). Additionally, only 1 patient reported gastric upset [in control group]. It seems that green tea extract might well be considered as an adjunctive treatment both for control of pain and for the betterment of knee joint physical function in adults with osteoarthritis. However, further studies of longer duration and larger sample size are needed. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  13. Sirolimus Use in Liver Transplant Recipients With Hepatocellular Carcinoma: A Randomized, Multicenter, Open-Label Phase 3 Trial

    Science.gov (United States)

    Geissler, Edward K.; Schnitzbauer, Andreas A.; Zülke, Carl; Lamby, Philipp E.; Proneth, Andrea; Duvoux, Christophe; Burra, Patrizia; Jauch, Karl-Walter; Rentsch, Markus; Ganten, Tom M.; Schmidt, Jan; Settmacher, Utz; Heise, Michael; Rossi, Giorgio; Cillo, Umberto; Kneteman, Norman; Adam, René; van Hoek, Bart; Bachellier, Philippe; Wolf, Philippe; Rostaing, Lionel; Bechstein, Wolf O.; Rizell, Magnus; Powell, James; Hidalgo, Ernest; Gugenheim, Jean; Wolters, Heiner; Brockmann, Jens; Roy, André; Mutzbauer, Ingrid; Schlitt, Angela; Beckebaum, Susanne; Graeb, Christian; Nadalin, Silvio; Valente, Umberto; Turrión, Victor Sánchez; Jamieson, Neville; Scholz, Tim; Colledan, Michele; Fändrich, Fred; Becker, Thomas; Söderdahl, Gunnar; Chazouillères, Olivier; Mäkisalo, Heikki; Pageaux, Georges-Philippe; Steininger, Rudolf; Soliman, Thomas; de Jong, Koert P.; Pirenne, Jacques; Margreiter, Raimund; Pratschke, Johann; Pinna, Antonio D.; Hauss, Johann; Schreiber, Stefan; Strasser, Simone; Klempnauer, Jürgen; Troisi, Roberto I.; Bhoori, Sherrie; Lerut, Jan; Bilbao, Itxarone; Klein, Christian G.; Königsrainer, Alfred; Mirza, Darius F.; Otto, Gerd; Mazzaferro, Vincenzo; Neuhaus, Peter; Schlitt, Hans J.

    2016-01-01

    Background We investigated whether sirolimus-based immunosuppression improves outcomes in liver transplantation (LTx) candidates with hepatocellular carcinoma (HCC). Methods In a prospective-randomized open-label international trial, 525 LTx recipients with HCC initially receiving mammalian target of rapamycin inhibitor–free immunosuppression were randomized 4 to 6 weeks after transplantation into a group on mammalian target of rapamycin inhibitor–free immunosuppression (group A: 264 patients) or a group incorporating sirolimus (group B: 261). The primary endpoint was recurrence-free survival (RFS); intention-to-treat (ITT) analysis was conducted after 8 years. Overall survival (OS) was a secondary endpoint. Results Recurrence-free survival was 64.5% in group A and 70.2% in group B at study end, this difference was not significant (P = 0.28; hazard ratio [HR], 0.84; 95% confidence interval [95% CI], 0.62; 1.15). In a planned analysis of RFS rates at yearly intervals, group B showed better outcomes 3 years after transplantation (HR, 0.7; 95% CI, 0.48-1.00). Similarly, OS (P = 0.21; HR, 0.81; 95% CI, 0.58-1.13) was not statistically better in group B at study end, but yearly analyses showed improvement out to 5 years (HR, 0.7; 95% CI, 0.49-1.00). Interestingly, subgroup (Milan Criteria-based) analyses revealed that low-risk, rather than high-risk, patients benefited most from sirolimus; furthermore, younger recipients (age ≤60) also benefited, as well sirolimus monotherapy patients. Serious adverse event numbers were alike in groups A (860) and B (874). Conclusions Sirolimus in LTx recipients with HCC does not improve long-term RFS beyond 5 years. However, a RFS and OS benefit is evident in the first 3 to 5 years, especially in low-risk patients. This trial provides the first high-level evidence base for selecting immunosuppression in LTx recipients with HCC. PMID:26555945

  14. Preliminary open-label clinical evaluation of the soothing and reepithelialization properties of a novel topical formulation for rosacea

    Directory of Open Access Journals (Sweden)

    Sparavigna A

    2014-10-01

    Full Text Available Adele Sparavigna, Beatrice Tenconi, Ileana De Ponti Derming Srl, Monza, Italy Background: Rosacea is a common, incurable skin barrier disorder characterized by relapses and remissions. Purpose: To evaluate the efficacy of Farmaka Rosacea Cream (FRC, a novel topical formulation for rosacea. Methods: This single-center, open-label pilot study comprised a single-dose substudy in 20 healthy subjects and a long-term, repeat-dose substudy in 22 subjects with rosacea. The 2-hour, controlled, single-dose substudy assessed the soothing and reepithelialization properties of FRC after stripping-induced erythema based on the erythema index, transepidermal water loss, skin hydration, and clinical assessments of erythema. In the long-term substudy, subjects applied FRC twice daily for 8 weeks. Clinical assessments included vascular and pigmentary homogeneity and erythema and hemoglobin indices. Subjects completed questionnaires to assess FRC efficacy and cosmetic acceptability. Results: Greater reductions were seen in FRC-treated areas compared with untreated areas for the erythema index (-16% versus -8%; P<0.001 and mean transepidermal water loss (-35.8% versus -10.1%; P<0.001 30 minutes after stripping. Significant improvements over untreated areas were maintained 2 hours after stripping. Skin hydration and clinical erythema assessments also indicated that FRC soothed rosacea symptoms and promoted skin reepithelialization. Erythema and hemoglobin indices were significantly reduced from baseline after 4 and 8 weeks of treatment. Clinically assessed parameters were significantly improved following FRC application. Subjects assessed FRC positively. Conclusion: Improvement of rosacea symptoms was noted with FRC application. The main film-forming ingredients of FRC (trehalose, cholesterol, ceramide, and fatty acids, combined with other soothing and calming ingredients and ultraviolet filters, could explain its efficacy. Keywords: rosacea, erythema, skin

  15. Long-term sequential deferiprone-deferoxamine versus deferiprone alone for thalassaemia major patients: a randomized clinical trial

    DEFF Research Database (Denmark)

    Maggio, Aurelio; Vitrano, Angela; Capra, Marcello

    2009-01-01

    A multicentre randomized open-label trial was designed to assess the effectiveness of long-term sequential deferiprone-deferoxamine (DFO-DFP) versus DFP alone to treat thalassaemia major (TM). DFP at 75 mg/kg, divided into three oral daily doses, for 4 d/week and DFO by subcutaneous infusion (8-1...

  16. Clinical and instrumental evaluation of a cross-linked hyaluronic acid filler dermal injection: effects on nasolabial folds skin biophysical parameters and augmentation from a single-dose, monocentric, open-label trial.

    Science.gov (United States)

    Cameli, Norma; Mariano, Maria; Serio, Mirko; Berardesca, Enzo

    2016-10-01

    When a hyaluronic acid dermal device to fill soft tissues is chosen, efficacy, safety and durability are key concerns. This is an open-label prospective study to instrumentally evaluate the effects of HA filler dermal injection on nasolabial folds skin biophysical parameters and augmentation. A single Italian site treated female subjects aged 40-55, for nasolabial folds, with a single standardized injection. The outcome was evaluated with objective quantitative measurements after 90 (T1) and 180 days (T2) from the injection comparing to baseline (T0) by means of Corneometer (skin hydration measurement), Cutometer (skin elasticity measurement), and Visioface devices for digital and UV computerized image analysis. Secondary endpoints were safety assessment, subject investigator satisfaction with the intervention. Assessment of aesthetic results included photographic documentation. The computerized image analysis confirmed the clinical assessment showing statistically significant reduction in nasolabial folds both at T1 and T2. Visioface® indexes showed a marked and statistical significant response. An excellent profile of satisfaction of the product at T2 from investigators and patients was recorded. Skin hydration and elasticity did not show significant changes. In our study, a standardized HA filler dermal injection on nasolabial folds did not influence skin biophysical parameters such as skin hydration and elasticity. Nasolabial folds showed a persistent and significative response at T2 confirmed by instrumental evaluation. The tolerability and safety profile of the product was excellent.

  17. Relative Bioavailability of Fixed-Dose Combinations of Tamsulosin and Dutasteride: Results From 2 Randomized Trials in Healthy Male Volunteers.

    Science.gov (United States)

    Burns, Olivia; Zhu, John; Manyak, Michael J; Ravindranath, Ramiya; Koosha, Fariba; Haque, Nazneen; Chung, Sally

    2018-05-01

    The relative bioavailabilities of dutasteride/tamsulosin hydrochloride 0.5 mg/0.2 mg fixed-dose combination (FDC) capsules compared with coadministered reference products (1 dutasteride 0.5-mg capsule [Avodart ® ] + 1 tamsulosin hydrochloride 0.2-mg orally disintegrating tablet [Harnal D ® ]) were investigated in 2 clinical trials under fasted and fed conditions (ClinicalTrials.gov NCT02184585 and NCT02509104). Both trials were open-label, randomized, single-dose, crossover studies in healthy male adults aged 18-65 years. Trial 1 evaluated 2 formulations (FDC1 and FDC2), and trial 2 evaluated a third formulation (FDC3). The primary end points were dutasteride area under the concentration-time curve from time 0 to t (AUC (0-t) ) and peak plasma concentration (C max ) and tamsulosin AUC (0-∞) , AUC (0-t) , and C max . The formulations were considered to be bioequivalent if the 90%CIs for the geometric mean ratios for each end point were within the range of 0.80-1.25. For FDC1 in trial 1, bioequivalence criteria were not met for dutasteride C max or AUC in the fasted state or for tamsulosin C max in the fasted or fed states. For FDC2 in trial 1, all bioequivalence criteria were met except for tamsulosin C max in the fasted state. For FDC3 in trial 2, bioequivalence criteria were met for all dutasteride and tamsulosin end points in both the fed and fasted states. Safety profiles were similar for all FDC formulations and combination treatments. © 2017, The American College of Clinical Pharmacology.

  18. A new label dosimetry system based on pentacosa-diynoic acid monomer for low dose applications

    International Nuclear Information System (INIS)

    Abdel-Fattah, A.A.; Abdel-Rehim, F.; Soliman, Y.S.

    2012-01-01

    The dosimetric characteristics of γ-radiation sensitive labels based on polyvinyl butyral (PVB) and a conjugated diacetylene monomer, 10,12-pentacosa-diynoic acid (PCDA) have been investigated using reflectance colorimeter. Two types of labels (colourless and yellow) based on PCDA monomer were prepared using an Automatic Film Applicator System. Upon γ-ray exposure, the colourless label turns progressively blue, while the yellow colour label turns to green then to dark blue. The colour intensity of the labels is proportional to the radiation absorbed dose. The useful dose range was 15 Gy-2 kGy depending on PCDA monomer concentration. The expanded uncertainty of dose measurement of the colourless label was 6.06 (2σ). - Highlights: → Using 10,12-pentacosa-diynoic acid (PCDA) in preparation of label dosimeter. → PCDA polymerises upon γ-rays exposure producing a blue coloured polymer. → Useful dose range is 15 Gy to 2 kGy depending on concentration of PCDA. → Overall uncertainty of label dosimeter was 6.06 at 2σ.

  19. A Single-Dose, Single-Period Pharmacokinetic Assessment of an Extended-Release Orally Disintegrating Tablet of Methylphenidate in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder.

    Science.gov (United States)

    Childress, Ann; Newcorn, Jeffrey; Stark, Jeffrey G; McMahen, Russ; Tengler, Mark; Sikes, Carolyn

    2016-08-01

    To determine the pharmacokinetic (PK) profile of a proprietary formulation of methylphenidate (MPH) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) in a phase 1 study. Methylphenidate extended-release orally disintegrating tablets (MPH XR-ODTs) combine two technologies in a single-tablet formulation-an extended-release profile that was designed for once-daily dosing in an ODT that does not require water or chewing for ingestion. This was a single-dose, open-label, single-period, single-treatment study, in which 32 children with ADHD who were receiving MPH in doses of 40 or 60 mg before beginning the study each received a 60-mg dose (2 × 30 mg) of MPH XR-ODT. The following plasma PK parameters of MPH were determined for participants grouped by age (6-7, 8-9, 10-12, and 13-17 years old): maximum concentration (Cmax), time to maximum concentration (Tmax), elimination half-life (T½), area under the curve from 0 hours to infinity (AUCinf), oral clearance (CL/F), and volume of distribution in the terminal phase (Vz/F). Safety and tolerability were also assessed. A total of 32 participants received the study drug. For all participants, plasma concentration-time profiles of MPH exhibited a broad peak after administration of MPH XR-ODT through ∼8 hours, indicating extended release from the formulation, followed by an apparent first-order elimination phase. As age increased, MPH exposure decreased and mean estimates of CL/F increased; however, weight-normalized CL/F values were comparable across age groups. Similarly, mean estimates of Vz/F increased with age, but weight-normalization decreased differences across age groups, with the exception of the youngest age group, which had higher values. All adverse events (AEs) were mild. This XR-ODT formulation of MPH demonstrated weight-normalized clearance rates that were consistent across all age groups, a PK profile consistent with once-daily dosing, and an AE profile consistent with

  20. An open-label extension study of the safety and efficacy of risperidone in children and adolescents with autistic disorder.

    Science.gov (United States)

    Kent, Justine M; Hough, David; Singh, Jaskaran; Karcher, Keith; Pandina, Gahan

    2013-12-01

    The purpose of this study was to evaluate the long-term safety and efficacy of risperidone in treating irritability and related behaviors in children and adolescents with autistic disorders. In this 6 month (26 week) open-label extension (OLE) study, patients (5-17 years of age, who completed the previous fixed-dose, 6 week, double-blind [DB] phase) were flexibly dosed with risperidone based on body weight. The maximum allowed dose was 1.25 mg/day for those weighing 20 to autistic, psychiatric, and behavioral disorders. Patients experienced some additional improvement in irritability and related behaviors. This phase-4 study is registered at ClinicalTrials.gov (NCT00576732).

  1. Efficacy of Lisdexamfetamine in Adults With Moderate to Severe Binge-Eating Disorder: A Randomized Clinical Trial.

    Science.gov (United States)

    Hudson, James I; McElroy, Susan L; Ferreira-Cornwell, M Celeste; Radewonuk, Jana; Gasior, Maria

    2017-09-01

    The ability of pharmacotherapies to prevent relapse and maintain efficacy with long-term treatment in psychiatric conditions is important. To assess lisdexamfetamine dimesylate maintenance of efficacy in adults with moderate to severe binge-eating disorder. A multinational, phase 3, double-blind, placebo-controlled, randomized withdrawal study including 418 participants was conducted at 49 clinical research study sites from January 27, 2014, to April 8, 2015. Eligible adults met DSM-IV-R binge-eating disorder criteria and had moderate to severe binge eating disorder (≥3 binge-eating days per week for 14 days before open-label baseline; Clinical Global Impressions-Severity [CGI-S] scores ≥4 [moderate severity] at screening and open-label baseline). Following a 12-week, open-label phase (dose optimization, 4 weeks [lisdexamfetamine dimesylate, 50 or 70 mg]; dose maintenance, 8 weeks), lisdexamfetamine responders (≤1 binge eating day per week for 4 consecutive weeks and CGI-S scores ≤2 at week 12) were randomized to placebo or continued lisdexamfetamine during a 26-week, double-blind, randomized withdrawal phase. Lisdexamfetamine administration. The primary outcome variable, time to relapse (≥2 binge-eating days per week for 2 consecutive weeks and ≥2-point CGI-S score increases from randomized withdrawal baseline), was analyzed using a log-rank test (primary analysis); the analysis was stratified for dichotomized 4-week cessation status. Safety assessments included treatment-emergent adverse events. Of the 418 participants enrolled in the open-label phase of the study, 411 (358 [87.1%] women; mean [SD] age, 38.3 [10.4] years) were included in the safety analysis set. Of 275 randomized lisdexamfetamine responders (placebo, n = 138; lisdexamfetamine, n = 137), the observed proportions of participants meeting relapse criteria were 3.7% (5 of 136) for lisdexamfetamine and 32.1% (42 of 131) for placebo. Lisdexamfetamine demonstrated superiority over

  2. Effect of novel inhaler technique reminder labels on the retention of inhaler technique skills in asthma: a single-blind randomized controlled trial.

    Science.gov (United States)

    Basheti, Iman A; Obeidat, Nathir M; Reddel, Helen K

    2017-02-09

    Inhaler technique can be corrected with training, but skills drop off quickly without repeated training. The aim of our study was to explore the effect of novel inhaler technique labels on the retention of correct inhaler technique. In this single-blind randomized parallel-group active-controlled study, clinical pharmacists enrolled asthma patients using controller medication by Accuhaler [Diskus] or Turbuhaler. Inhaler technique was assessed using published checklists (score 0-9). Symptom control was assessed by asthma control test. Patients were randomized into active (ACCa; THa) and control (ACCc; THc) groups. All patients received a "Show-and-Tell" inhaler technique counseling service. Active patients also received inhaler labels highlighting their initial errors. Baseline data were available for 95 patients, 68% females, mean age 44.9 (SD 15.2) years. Mean inhaler scores were ACCa:5.3 ± 1.0; THa:4.7 ± 0.9, ACCc:5.5 ± 1.1; THc:4.2 ± 1.0. Asthma was poorly controlled (mean ACT scores ACCa:13.9 ± 4.3; THa:12.1 ± 3.9; ACCc:12.7 ± 3.3; THc:14.3 ± 3.7). After training, all patients had correct technique (score 9/9). After 3 months, there was significantly less decline in inhaler technique scores for active than control groups (mean difference: Accuhaler -1.04 (95% confidence interval -1.92, -0.16, P = 0.022); Turbuhaler -1.61 (-2.63, -0.59, P = 0.003). Symptom control improved significantly, with no significant difference between active and control patients, but active patients used less reliever medication (active 2.19 (SD 1.78) vs. control 3.42 (1.83) puffs/day, P = 0.002). After inhaler training, novel inhaler technique labels improve retention of correct inhaler technique skills with dry powder inhalers. Inhaler technique labels represent a simple, scalable intervention that has the potential to extend the benefit of inhaler training on asthma outcomes. REMINDER LABELS IMPROVE INHALER TECHNIQUE: Personalized

  3. Maternal vitamin D supplementation during pregnancy prevents vitamin D deficiency in the newborn: an open-label randomized controlled trial.

    Science.gov (United States)

    Rodda, C P; Benson, J E; Vincent, A J; Whitehead, C L; Polykov, A; Vollenhoven, B

    2015-09-01

    To determine whether maternal vitamin D supplementation, in the vitamin D deficient mother, prevents neonatal vitamin D deficiency. Open-label randomized controlled trial. Metropolitan Melbourne, Australia, tertiary hospital routine antenatal outpatient clinic. Seventy-eight women with singleton pregnancies with vitamin D deficiency/insufficiency (serum 25-OH Vit D l) at their first antenatal appointment at 12-16-week gestation were recruited. Participants were randomized to vitamin D supplementation (2000-4000 IU cholecalciferol) orally daily until delivery or no supplementation. The primary outcome was neonatal serum 25-OH vit D concentration at delivery. The secondary outcome was maternal serum 25-OH vit D concentration at delivery. Baseline mean maternal serum 25-OH vit D concentrations were similar (P = 0·9) between treatment (32 nmol/l, 95% confidence interval 26-39 nmol/l) and control groups (33 nmol/l, 95% CI 26-39 nmol/l). Umbilical cord serum 25-OH vit D concentrations at delivery were higher (P l, 95% CI; 70-91 nmol/l) compared with neonates of control group mothers (42 nmol/l, 95% CI; 34-50 nmol/l) with a strongly positive correlation between maternal serum 25-OH Vit D and umbilical cord serum 25-OH vit D concentrations at delivery (Spearman rank correlation coefficient 0·88; P l, 95% CI; 62-81 nmol/l) compared with the control group (36 nmol/l, 95% CI; 29-42 nmol/l). Vitamin D supplementation of vitamin D deficient pregnant women prevents neonatal vitamin D deficiency. © 2015 John Wiley & Sons Ltd.

  4. Daily consumption of fermented soymilk helps to improve facial wrinkles in healthy postmenopausal women in a randomized, parallel-group, open-label trial

    Directory of Open Access Journals (Sweden)

    Mitsuyoshi Kano

    2018-02-01

    Full Text Available Background: Soymilk fermented by lactobacilli and/or bifidobacteria is attracting attention due to the excellent bioavailability of its isoflavones. We investigated the effects of fermented soymilk containing high amounts of isoflavone aglycones on facial wrinkles and urinary isoflavones in postmenopausal women in a randomized, parallel-group, open-label trial. Healthy Japanese women were randomly divided into active (n = 44, mean age 56.3 ± 0.5 or control (n = 44, mean age 56.1 ± 0.5 groups, who consumed or did not consume a bottle of soymilk fermented by Bifidobacterium breve strain Yakult and Lactobacillus mali for 8 weeks. Maximum depth of wrinkles around the crow’s feet area and other wrinkle parameters were evaluated as primary and secondary endpoints respectively at weeks 0, 4, and 8 during the consumption period. Urinary isoflavone levels were determined by liquid chromatography-mass spectrometry. Results: The active group demonstrated significant improvements in the maximum depth (p=0.015 and average depth (p=0.04 of wrinkles, and significantly elevated urinary isoflavones (daidzein, genistein, and glycitein; each p < 0.001 compared with the control during the consumption period. No serious adverse effects were recorded. Conclusion: These findings suggest that fermented soymilk taken daily may improve facial wrinkles and elevate urinary isoflavones in healthy postmenopausal women.

  5. Phase II open-label study to assess efficacy and safety of lenalidomide in combination with cetuximab in KRAS-mutant metastatic colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Salvatore Siena

    Full Text Available This study aimed to assess the efficacy and safety of combination treatment with lenalidomide and cetuximab in KRAS-mutant metastatic colorectal cancer patients. This was a phase II multicenter, open-label trial comprising a safety lead-in phase (phase IIa to determine the maximum tolerated dose, and a randomized proof of concept phase (phase IIb to determine the response rate of lenalidomide plus cetuximab combination therapy. Phase IIa treatment comprised oral lenalidomide (starting dose 25 mg/day and intravenous cetuximab (400 mg/m(2 followed by weekly 250 mg/m(2 in 28-day cycles. In phase IIb patients were randomized to either the phase IIa treatment schedule of lenalidomide plus cetuximab combination therapy or lenalidomide 25 mg/day monotherapy. Eight patients were enrolled into phase IIa. One patient developed a dose-limiting toxicity and the maximum tolerated dose of lenalidomide was determined at 25 mg/day. Forty-three patients were enrolled into phase IIb proof of concept. Best response was stable disease in 9 patients and study enrollment was terminated prematurely due to lack of efficacy in both treatment arms and failure to achieve the planned response objective. The majority of adverse events were grade 1 and 2. In both phases, the adverse events most commonly attributed to any study drugs were fatigue, rash and other skin disorders, diarrhea, nausea, and stomatitis. Thirty-nine deaths occurred; none was related to study drug. The combination of lenalidomide and cetuximab appeared to be well tolerated but did not have clinically meaningful activity in KRAS-mutant metastatic colorectal cancer patients.Clinicaltrials.gov NCT01032291.

  6. Add-on-Statin Extended Release Nicotinic Acid/Laropiprant but Not the Switch to High-Dose Rosuvastatin Lowers Blood Pressure: An Open-Label Randomized Study

    Directory of Open Access Journals (Sweden)

    Anastazia Kei

    2011-01-01

    Full Text Available Introduction. Nicotinic acid (NA and statins have been associated with reductions in blood pressure (BP. Patients and Methods. We recruited 68 normotensive and hypertensive dyslipidemic patients who were treated with a conventional statin dose and had not achieved lipid targets. Patients were randomized to switch to high-dose rosuvastatin (40 mg/day or to add-on current statin treatment with extended release (ER NA/laropiprant (1000/20 mg/day for the first 4 weeks followed by 2000/40 mg/day for the next 8 weeks for 3 months. Results. Switching to rosuvastatin 40 mg/day was not associated with significant BP alterations. In contrast, the addition of ER-NA/laropiprant to current statin treatment resulted in a 7% reduction of systolic BP (from 134±12 to 125±10 mmHg, <.001 versus baseline and =.01 versus rosuvastatin group and a 5% reduction of diastolic BP (from 81±9 to 77±6 mmHg, =.009 versus baseline and =.01 versus rosuvastatin group. These reductions were significant only in the subgroup of hypertensives and were independent of the hypolipidemic effects of ER-NA/laropiprant. Conclusions. Contrary to the switch to high-dose rosuvastatin, the addition of ER-NA/laropiprant to statin treatment was associated with significant reductions in both systolic and diastolic BP.

  7. Comparative efficacy trial of cupping and serkangabin versus conventional therapy of migraine headaches: A randomized, open-label, comparative efficacy trial.

    Science.gov (United States)

    Firoozabadi, Mohammad Dehghani; Navabzadeh, Maryam; Roudsari, Mohammad Khodashenas; Zahmatkash, Mohsen

    2014-12-01

    Migraine headaches are the most common acute and recurrent headaches. Current treatment of a migraine headache consists of multiple medications for control and prevention of recurrent attacks. Global emergence of alternative medicine led us to examine the efficacy of cupping therapy plus serkangabin syrup in the treatment of migraine headaches. This study was a randomized, controlled, open-label, comparative efficacy trial. We randomly assigned patients with migraine into cupping therapy plus serkangabin group (30 patients) and conventional treatment group (30 patients). An investigator assessed the severity of headache, frequency of attacks in a week and duration of attacks per hour in 5 visits (at the end of 2 weeks, 1, 3 and 6 months). Generalized estimating equations approach was used to analyze repeated measures data to compare outcomes in both groups. Average age for cupping therapy group and conventional treatment group were 31.7 (±7.6) and 32.6 (±12.7) years, respectively (P = 0.45). After treatment for 2 weeks; and 1, 3 and 6 months, severity of headache (P = 0.80), frequency of migraine attacks (P = 0.63) and duration of attacks per hours (P = 0.48) were similar in conventional and cupping groups but these symptoms were decreased in each group during the study (P cupping plus serkangabin therapy and conventional treatment in the treatment and prophylaxis of migraine. The alternative therapy may be used in cases of drug intolerance, no medication response, and in primary care.

  8. An open-label dose escalation study to evaluate the safety of administration of nonviral stromal cell-derived factor-1 plasmid to treat symptomatic ischemic heart failure.

    Science.gov (United States)

    Penn, Marc S; Mendelsohn, Farrell O; Schaer, Gary L; Sherman, Warren; Farr, Maryjane; Pastore, Joseph; Rouy, Didier; Clemens, Ruth; Aras, Rahul; Losordo, Douglas W

    2013-03-01

    Preclinical studies indicate that adult stem cells induce tissue repair by activating endogenous stem cells through the stromal cell-derived factor-1:chemokine receptor type 4 axis. JVS-100 is a DNA plasmid encoding human stromal cell-derived factor-1. We tested in a phase 1, open-label, dose-escalation study with 12 months of follow-up in subjects with ischemic cardiomyopathy to see if JVS-100 improves clinical parameters. Seventeen subjects with ischemic cardiomyopathy, New York Heart Association class III heart failure, with an ejection fraction ≤40% on stable medical therapy, were enrolled to receive 5, 15, or 30 mg of JVS-100 via endomyocardial injection. The primary end points for safety and efficacy were at 1 and 4 months, respectively. The primary safety end point was a major adverse cardiac event. Efficacy end points were change in quality of life, New York Heart Association class, 6-minute walk distance, single photon emission computed tomography, N-terminal pro-brain natruretic peptide, and echocardiography at 4 and 12 months. The primary safety end point was met. At 4 months, all of the cohorts demonstrated improvements in 6-minute walk distance, quality of life, and New York Heart Association class. Subjects in the 15- and 30-mg dose groups exhibited improvements in 6-minute walk distance (15 mg: median [range]: 41 minutes [3-61 minutes]; 30 mg: 31 minutes [22-74 minutes]) and quality of life (15 mg: -16 points [+1 to -32 points]; 30 mg: -24 points [+17 to -38 points]) over baseline. At 12 months, improvements in symptoms were maintained. These data highlight the importance of defining the molecular mechanisms of stem cell-based tissue repair and suggest that overexpression of stromal cell-derived factor-1 via gene therapy is a strategy for improving heart failure symptoms in patients with ischemic cardiomyopathy.

  9. Effectiveness of one-year pharmacological treatment of adult attention-deficit/hyperactivity disorder (ADHD): an open-label prospective study of time in treatment, dose, side-effects and comorbidity.

    Science.gov (United States)

    Fredriksen, Mats; Dahl, Alv A; Martinsen, Egil W; Klungsøyr, Ole; Haavik, Jan; Peleikis, Dawn E

    2014-12-01

    How to generalize from randomized placebo controlled trials of ADHD drug treatment in adults to 'real-world' clinical practice is intriguing. This open-labeled prospective observational study examined the effectiveness of long-term stimulant and non-stimulant medication in adult ADHD including dose, side-effects and comorbidity in a clinical setting. A specialized ADHD outpatient clinic gave previously non-medicated adults (n=250) with ADHD methylphenidate as first-line drug according to current guidelines. Patients who were non-tolerant or experiencing low efficacy were switched to amphetamine or atomoxetine. Primary outcomes were changes of ADHD-symptoms evaluated with the Adult ADHD Self-Report Scale (ASRS) and overall severity by the Global Assessment of Functioning (GAF). Secondary outcomes were measures of mental distress, and response on the Clinical-Global-Impressions-Improvement Scale. Data at baseline and follow-ups were compared in longitudinal mixed model analyses for time on-medication, dosage, comorbidity, and side-effects. As results, 232 patients (93%) completed examination at the 12 month endpoint, and 163 (70%) remained on medication. Compared with the patients who discontinued medication, those still on medication had greater percentage reduction in ASRS-scores (median 39%, versus 13%, Ptreatment with stimulants or atomoxetine was associated with a clinically significant reduction in ADHD symptoms and mental distress, and improvement of measured function. No serious adverse events were observed. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

  10. Dataset for Phase I randomized clinical trial for safety and tolerability of GET 73 in single and repeated ascending doses including preliminary pharmacokinetic parameters

    Directory of Open Access Journals (Sweden)

    Carolina L. Haass-Koffler

    2017-12-01

    Full Text Available The data in this article outline the methods used for the administration of GET 73 in the first time-in-human manuscript entitled “Phase I randomized clinical trial for the safety, tolerability and preliminary pharmacokinetics of the mGluR5 negative allosteric modulator GET 73 following single and repeated doses in healthy male volunteers” (Haass-Koffler et al., 2017 [1]. Data sets are provided in two different manners. The first series of tables provided includes procedural information about the experiments conducted. The next series of tables provided includes Pharmacokinetic (PK parameters for GET 73 and its main metabolite MET 2. This set of data is comprised by two experiments: Experiment 1 references a single ascending dose administration of GET 73 and Experiment 2 references a repeated ascending dose administration of GET 73. Keywords: Glutamate receptor subtype 5 (mGlu5, Allosteric modulator, GET 73, Safety, Tolerability

  11. Single and Multiple Ascending-dose Studies of Oral Delafloxacin: Effects of Food, Sex, and Age.

    Science.gov (United States)

    Hoover, Randall; Hunt, Thomas; Benedict, Michael; Paulson, Susan K; Lawrence, Laura; Cammarata, Sue; Sun, Eugene

    2016-01-01

    The objective of this report is describe the results of 2 studies that examined the pharmacokinetic parameters, safety profile, and tolerability of single and multiple ascending doses of oral delafloxacin and the effects of food, sex, and age on oral delafloxacin pharmacokinetic parameters, safety profile, and tolerability. The first study contained 3 parts and used unformulated delafloxacin in a capsule. Part 1 was a randomized, double-blind, placebo-controlled, single (50, 100, 200, 400, 800, 1200, and 1600 mg) ascending-dose study of oral delafloxacin in healthy men. Part 2 was a single-dose crossover study in which 20 men received 250 mg delafloxacin with or without food. Part 2 also included a parallel group, double-blind, placebo-controlled study in 16 women and 16 elderly men and women who were randomized (3:1) to receive 250 mg delafloxacin or placebo. Part 3 was a randomized, double-blind, placebo-controlled, multiple (100, 200, 400, 800, 1200 mg once daily for 5 days) ascending-dose study of oral delafloxacin in healthy men. The second study was a single-dose, randomized, 3-period crossover study in which participants received 900 mg delafloxacin (2 × 450-mg tablets) under fasted conditions, with a high-fat meal, or fasted with a high-fat meal 2 hours after dosing. Serial blood samples were collected, and plasma pharmacokinetic parameters of delafloxacin were determined. Delafloxacin Cmax and AUC0-∞ increased with increasing oral dose over the dose range of 50 to 1600 mg. The increases in delafloxacin AUC0-∞ were dose proportional at doses of ≥200 mg. Steady state was reached by day 3 of dosing with minimal accumulation of delafloxacin. The Cmax of delafloxacin was decreased slightly in the presence of food. No sex difference in delafloxacin pharmacokinetic parameters was observed. In the elderly men and women, mean delafloxacin Cmax and AUC0-∞ were 35% higher than observed for young adults, which could be partially explained by a decrease in

  12. GSK1265744 pharmacokinetics in plasma and tissue after single-dose long-acting injectable administration in healthy subjects.

    Science.gov (United States)

    Spreen, William; Ford, Susan L; Chen, Shuguang; Wilfret, David; Margolis, David; Gould, Elizabeth; Piscitelli, Stephen

    2014-12-15

    GSK1265744 (744) is an HIV-1 integrase inhibitor in clinical development as a long-acting (LA) injectable formulation. This study evaluated plasma and tissue pharmacokinetics after single-dose administration of 744 LA administered by intramuscular (IM) or subcutaneous injections. This was a phase I, open-label, 9-cohort, parallel study of 744 in healthy subjects. 744 was administered as a 200 mg/mL nanosuspension at doses of 100-800 mg IM and 100-400 mg subcutaneous. Eight (6 active and 2 placebo) male and female subjects participated in each of the first 7 cohorts. All 8 subjects, 4 males and 4 females, received active 744 LA in cohorts 8 and 9 and underwent rectal and cervicovaginal tissue sampling, respectively. Plasma pharmacokinetic sampling was performed for a minimum of 12 weeks or until 744 concentrations were ≤0.1 μg/mL. Rectal and cervicovaginal tissue biopsies were performed at weeks 2 and 8 (cohort 8) and weeks 4 and 12 (cohort 9). 744 LA was generally safe and well tolerated after single injections. A majority of subjects reported injection site reactions, all graded as mild in intensity. Plasma concentration-time profiles were prolonged with measureable concentrations up to 52 weeks after dosing. 744 LA 800 mg IM achieved mean concentrations above protein adjusted-IC90 for approximately 16 weeks. Rectal and cervicovaginal tissue concentrations ranged from injection has potential application as a monthly or less frequent HIV treatment or prevention agent.

  13. Effect of Low-Dose (Single-Dose Magnesium Sulfate on Postoperative Analgesia in Hysterectomy Patients Receiving Balanced General Anesthesia

    Directory of Open Access Journals (Sweden)

    Arman Taheri

    2015-01-01

    Full Text Available Background and Aim. Aparallel, randomized, double blinded, placebo-controlled trial study was designed to assess the efficacy of single low dose of intravenous magnesium sulfate on post-total abdominal hysterectomy (TAH pain relief under balanced general anesthesia. Subject and Methods. Forty women undergoing TAH surgery were assigned to two magnesium sulfate (N=20 and normal saline (N=20 groups randomly. The magnesium group received magnesium sulfate 50 mg·kg−1 in 100 mL of normal saline solution i.v as single-dose, just 15 minutes before induction of anesthesia whereas patients in control group received 100 mL of 0.9% sodium chloride solution at the same time. The same balanced general anesthesia was induced for two groups. Pethidine consumption was recorded over 24 hours precisely as postoperative analgesic. Pain score was evaluated with Numeric Rating Scale (NRS at 0, 6, 12, and 24 hours after the surgeries. Results. Postoperative pain score was lower in magnesium group at 6, 12, and 24 hours after the operations significantly (P<0.05. Pethidine requirement was significantly lower in magnesium group throughout 24 hours after the surgeries (P=0.0001. Conclusion. Single dose of magnesium sulfate during balanced general anesthesia could be considered as effective and safe method to reduce postoperative pain and opioid consumption after TAH.

  14. A Randomized Study Comparing Outcomes of Stapled and Hand-Sutured Anastomoses in Patients Undergoing Open Gastrointestinal Surgery

    OpenAIRE

    Chandramohan, S. M.; Gajbhiye, Raj Narenda; Agwarwal, Anil; Creedon, Erin; Schwiers, Michael L.; Waggoner, Jason R.; Tatla, Daljit

    2012-01-01

    Although stapling is an alternative to hand-suturing in gastrointestinal surgery, recent trials specifically designed to evaluate differences between the two in surgery time, anastomosis time, and return to bowel activity are lacking. This trial compared the outcomes of the two in subjects undergoing open gastrointestinal surgery. Adult subjects undergoing emergency or elective surgery requiring a single gastric, small, or large bowel anastomosis were enrolled into this open-label, prospectiv...

  15. A randomized study of the effects of single-dose gabapentin versus placebo on postoperative pain and morphine consumption after mastectomy

    DEFF Research Database (Denmark)

    Dirks, Jesper; Fredensborg, Birgitte B; Christensen, Dennis

    2002-01-01

    BACKGROUND: The anticonvulsant gabapentin has proven effective for neuropathic pain in three large placebo-controlled clinical trials. Experimental and clinical studies have demonstrated antihyperalgesic effects in models involving central neuronal sensitization. It has been suggested that central...... neuronal sensitization may play an important role in postoperative pain. The aim of the study was to investigate the effect of gabapentin on morphine consumption and postoperative pain in patients undergoing radical mastectomy. METHODS: In a randomized, double-blind, placebo-controlled study, 70 patients...... received a single dose of oral gabapentin (1,200 mg) or placebo 1 h before surgery. Patients received patient-controlled analgesia with morphine at doses of 2.5 mg with a lock-out time of 10 min for 4 h postoperatively. Pain was assessed on a visual analog scale at rest and during movement, and side...

  16. A randomized, double-blind, placebo-controlled trial of single-dose ciprofloxacin versus erythromycin for the treatment of chancroid in Nairobi, Kenya.

    Science.gov (United States)

    Malonza, I M; Tyndall, M W; Ndinya-Achola, J O; Maclean, I; Omar, S; MacDonald, K S; Perriens, J; Orle, K; Plummer, F A; Ronald, A R; Moses, S

    1999-12-01

    A randomized, double-blind, placebo-controlled clinical trial was conducted in Nairobi, Kenya, to compare single-dose ciprofloxacin with a 7-day course of erythromycin for the treatment of chancroid. In all, 208 men and 37 women presenting with genital ulcers clinically compatible with chancroid were enrolled. Ulcer etiology was determined using culture techniques for chancroid, serology for syphilis, and a multiplex polymerase chain reaction for chancroid, syphilis, and herpes simplex virus (HSV). Ulcer etiology was 31% unmixed chancroid, 23% unmixed syphilis, 16% unmixed HSV, 15% mixed etiology, and 15% unknown. For 111 participants with chancroid, cure rates were 92% with ciprofloxacin and 91% with erythromycin. For all study participants, the treatment failure rate was 15%, mostly related to ulcer etiologies of HSV infection or syphilis, and treatment failure was 3 times more frequent in human immunodeficiency virus-infected subjects than in others, mostly owing to HSV infection. Ciprofloxacin is an effective single-dose treatment for chancroid, but current recommendations for empiric therapy of genital ulcers may result in high treatment failure due to HSV infection.

  17. Pharmacokinetics, Safety and Tolerability of Sacubitril/Valsartan (LCZ696) After Single-Dose Administration in Healthy Chinese Subjects.

    Science.gov (United States)

    Han, Yi; Ayalasomayajula, Surya; Pan, Wei; Yang, Fan; Yuan, Yaozong; Langenickel, Thomas; Hinder, Markus; Kalluri, Sampath; Pal, Parasar; Sunkara, Gangadhar

    2017-02-01

    Sacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor (ARNI) and has been recently approved in several countries for the treatment of patients with heart failure and reduced ejection fraction. This was the first study conducted to characterise the pharmacokinetics of LCZ696 analytes (pro-drug sacubitril, active neprilysin inhibitor LBQ657 and valsartan) after single-dose administration of LCZ696 in healthy Chinese subjects. In this open-label, randomised, parallel-group study, following screening and baseline evaluation, eligible healthy subjects received single oral doses of LCZ696 50, 100, 200 or 400 mg. The pharmacokinetics, safety and tolerability of LCZ696 were assessed up to 72 h after dosing. A total of 40 healthy male subjects were enrolled, and all completed the study. Following oral administration, LCZ696 delivered systemic exposure to sacubitril, LBQ657 and valsartan with a median time to reach maximum plasma concentration (T max ) ranging from 0.50 to 1.25, 2.00 to 3.00 and 1.50 to 2.50 h, respectively, over the investigated dose range. The mean terminal elimination half-life (T 1/2 ) ranged from 0.89 to 1.35, 8.57 to 9.24 and 5.33 to 7.91 h for sacubitril, LBQ657 and valsartan, respectively. The area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUC 0-last ), and maximum plasma concentration (C max ) for LBQ657 increased dose proportionally over the entire dose range. Dose linear increase in the exposure was observed across the dose range for sacubitril and valsartan. LCZ696 was safe and well tolerated at all doses in this study. Adverse events of only mild intensity, which required no treatment, were reported in 6 (15 %) subjects. The pharmacokinetic profiles of LCZ696 analytes in Chinese subjects are similar to those reported previously in Caucasian subjects.

  18. Single- and multiple-dose pharmacokinetics, pharmacodynamics, and safety of apixaban in healthy Chinese subjects

    Directory of Open Access Journals (Sweden)

    Cui Y

    2013-12-01

    Full Text Available Yimin Cui,1 Yan Song,2 Jessie Wang,2 Zhigang Yu,2 Alan Schuster,2 Yu Chen Barrett,2 Charles Frost2 1Peking University First Hospital, Beijing, People's Republic of China; 2Bristol-Myers Squibb, Princeton, NJ, USA Background: The pharmacokinetics (PK, pharmacodynamics (PD, and safety of apixaban were assessed in healthy Chinese subjects in this randomized, placebo-controlled, double-blind, single-sequence, single- and multiple-dose study. Subjects and methods: Eighteen subjects 18–45 years of age were randomly assigned (2:1 ratio to receive apixaban or matched placebo. Subjects received a single 10 mg dose of apixaban or placebo on day 1, followed by 10 mg apixaban or placebo twice daily for 6 days (days 4–9. The PK and PD of apixaban were assessed by collecting plasma samples for 72 hours following the dose on day 1 and the morning dose on day 9, and measuring apixaban concentration and anti-Xa activity. Safety was assessed via physical examinations, vital sign measurements, electrocardiograms, and clinical laboratory evaluations. Results: PK analysis showed similar characteristics of apixaban after single and multiple doses, including a median time to maximum concentration of ~3 hours, mean elimination half-life of ~11 hours, and renal clearance of ~1.2 L/hour. The accumulation index was 1.7, consistent with twice-daily dosing and the observed elimination half-life. Single-dose data predict multiple-dose PK, therefore apixaban PK are time-independent. The relationship between anti-Xa activity and plasma apixaban concentrations appears to be linear. Apixaban was safe and well tolerated, with no bleeding-related adverse events reported. Conclusion: Apixaban was safe and well tolerated in healthy Chinese subjects. Apixaban PK and PD were predictable and consistent with findings from previous studies in Asian and non-Asian subjects. The administration of apixaban does not require any dose modification based on race. Keywords: apixaban, oral

  19. Modest blood pressure reduction with valsartan in acute ischemic stroke: a prospective, randomized, open-label, blinded-end-point trial.

    Science.gov (United States)

    Oh, Mi Sun; Yu, Kyung-Ho; Hong, Keun-Sik; Kang, Dong-Wha; Park, Jong-Moo; Bae, Hee-Joon; Koo, Jaseong; Lee, Juneyoung; Lee, Byung-Chul

    2015-07-01

    To assess the efficacy and safety of modest blood pressure (BP) reduction with valsartan within 48 h after symptom onset in patients with acute ischemic stroke and high BP. This was a multicenter, prospective, randomized, open-label, blinded-end-point trial. A total of 393 subjects were recruited at 28 centers and then randomly assigned in a 1:1 ratio to receive valsartan (n = 195) or no treatment (n = 198) for seven-days after presentation. The primary outcome was death or dependency, defined as a score of 3-6 on the modified Rankin Scale (mRS) at 90 days after symptom onset. Early neurological deterioration (END) within seven-days and 90-day major vascular events were also assessed. There were 372 patients who completed the 90-day follow-up. The valsartan group had 46 of 187 patients (24·6%) with a 90-day mRS 3-6, compared with 42 of 185 patients (22·6%) in the control group (odds ratio [OR], 1·11; 95% confidence interval [CI], 0·69-1·79; P = 0·667). The rate of major vascular events did not differ between groups (OR, 1·41; 95% CI, 0·44-4·49; P = 0·771). There was a significant increase of END in the valsartan group (OR, 2·43; 95% CI, 1·25-4·73; P = 0·008). Early reduction of BP with valsartan did not reduce death or dependency and major vascular events at 90 days, but increased the risk of END. © 2015 World Stroke Organization.

  20. The pharmacokinetic profile of a novel fixed-dose combination tablet of ibuprofen and paracetamol

    OpenAIRE

    Tanner, Trevor; Aspley, Sue; Munn, Andrew; Thomas, Tracy

    2010-01-01

    Background Ibuprofen and paracetamol differ in their mode of action and related therapeutic effects, suggesting that combined administration may offer improved analgesia. Reported here are the results of two studies on the pharmacokinetic properties of a novel ibuprofen (200 mg) and paracetamol (500 mg) fixed-dose combination tablet. Methods Both studies were open-label, randomised studies in healthy volunteers: Study 1 was a four-way crossover, single-dose study; Study 2 was a two-way cross-...

  1. A molecular beacon microarray based on a quantum dot label for detecting single nucleotide polymorphisms.

    Science.gov (United States)

    Guo, Qingsheng; Bai, Zhixiong; Liu, Yuqian; Sun, Qingjiang

    2016-03-15

    In this work, we report the application of streptavidin-coated quantum dot (strAV-QD) in molecular beacon (MB) microarray assays by using the strAV-QD to label the immobilized MB, avoiding target labeling and meanwhile obviating the use of amplification. The MBs are stem-loop structured oligodeoxynucleotides, modified with a thiol and a biotin at two terminals of the stem. With the strAV-QD labeling an "opened" MB rather than a "closed" MB via streptavidin-biotin reaction, a sensitive and specific detection of label-free target DNA sequence is demonstrated by the MB microarray, with a signal-to-background ratio of 8. The immobilized MBs can be perfectly regenerated, allowing the reuse of the microarray. The MB microarray also is able to detect single nucleotide polymorphisms, exhibiting genotype-dependent fluorescence signals. It is demonstrated that the MB microarray can perform as a 4-to-2 encoder, compressing the genotype information into two outputs. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Evidence for single-dose protection by the bivalent HPV vaccine-Review of the Costa Rica HPV vaccine trial and future research studies.

    Science.gov (United States)

    Kreimer, Aimée R; Herrero, Rolando; Sampson, Joshua N; Porras, Carolina; Lowy, Douglas R; Schiller, John T; Schiffman, Mark; Rodriguez, Ana Cecilia; Chanock, Stephen; Jimenez, Silvia; Schussler, John; Gail, Mitchell H; Safaeian, Mahboobeh; Kemp, Troy J; Cortes, Bernal; Pinto, Ligia A; Hildesheim, Allan; Gonzalez, Paula

    2018-01-20

    The Costa Rica Vaccine Trial (CVT), a phase III randomized clinical trial, provided the initial data that one dose of the HPV vaccine could provide durable protection against HPV infection. Although the study design was to administer all participants three doses of HPV or control vaccine, 20% of women did not receive the three-dose regimens, mostly due to involuntary reasons unrelated to vaccination. In 2011, we reported that a single dose of the bivalent HPV vaccine could be as efficacious as three doses of the vaccine using the endpoint of persistent HPV infection accumulated over the first four years of the trial; findings independently confirmed in the GSK-sponsored PATRICIA trial. Antibody levels after one dose, although lower than levels elicited by three doses, were 9-times higher than levels elicited by natural infection. Importantly, levels remained essentially constant over at least seven years, suggesting that the observed protection provided by a single dose might be durable. Much work has been done to assure these non-randomized findings are valid. Yet, the group of recipients who received one dose of the bivalent HPV vaccine in the CVT and PATRICIA trials was small and not randomly selected nor blinded to the number of doses received. The next phase of research is to conduct a formal randomized, controlled trial to evaluate the protection afforded by a single dose of HPV vaccine. Complementary studies are in progress to bridge our findings to other populations, and to further document the long-term durability of antibody response following a single dose. Published by Elsevier Ltd.

  3. Cluster Randomized Trail of the uptake of a take-home Infant dose ...

    African Journals Online (AJOL)

    Objective: To test whether a single take home dose of infant nevirapine increased infant uptake without decreasing institutional deliveries. Design: Cluster randomized post-test only study with control group. Setting: Ten hospitals in urban areas of Coast, Rift Valley, and Western provinces, Kenya. Participants: Pregnant ...

  4. Role of signal dose preoperative antibiotic in acute nonperforated appendicitics

    International Nuclear Information System (INIS)

    Malik, S.A.; Rasheed, M.; Abbasi, A.S.; Iqbal, R.A.; Mian, M.A.

    2013-01-01

    Objective: To determine the efficacy of a single dose of preoperative antibiotic in preventing post operative infective complications in patients undergoing appendicectomy for non perforated acute appendicitis. Study Design: Randomized controlled trials. Place and Duration of Study: Surgical unit I and II, department of General Surgery, Combined Military Hospital (CMH) Lahore from 1st June to 31st October 2010. Patients and Methods: Seventy patients with acute appendicitis scheduled for appendicectomy were included in the study and randomly divided into two groups of 35 each using random numbers table. Group A received single dose preoperative antibiotic and group B received three-dose regimens of cefuroxime. Postoperative infective complications were the primary endpoint. Results: The rate of postoperative wound infection was not statistically insignificantly different among the groups; (8.57%) group A and (5.71%) group B at 1st post operative week and (5.71%) group A and (5.71%) group B at 2nd post operative week. None of the patients from either group showed any signs of intra abdominal abscess formation. Conclusion: Single dose of preoperative antibiotics is adequate for prevention of postoperative infective complications in patients with non-perforated appendicitis undergoing open appendicectomy. (author)

  5. Switching from rivaroxaban to warfarin: an open label pharmacodynamic study in healthy subjects

    Science.gov (United States)

    Moore, Kenneth Todd; Byra, William; Vaidyanathan, Seema; Natarajan, Jaya; Ariyawansa, Jay; Salih, Hiba; Turner, Kenneth C

    2015-01-01

    Aims The primary objective was to explore the pharmacodynamic changes during transition from rivaroxaban to warfarin in healthy subjects. Safety, tolerability and pharmacokinetics were assessed as secondary objectives. Methods An open label, non-randomized, sequential two period study. In treatment period 1 (TP1), subjects received rivaroxaban 20 mg once daily (5 days), followed by co-administration with a warfarin loading dose regimen of 5 or 10 mg (for the 10 mg regimen, the dose could be uptitrated to attain target international normalized ratio [INR] ≥2.0) once daily (2–4 days). When trough INR values ≥2.0 were attained, rivaroxaban was discontinued and warfarin treatment continued as monotherapy (INR 2.0–3.0). During treatment period 2, subjects received the same warfarin regimen as in TP1, but without rivaroxaban. Results During co-administration, maximum INR and prothrombin time (PT) values were higher than with rivaroxaban or warfarin monotherapy. The mean maximum effect (Emax) for INR after co-administration was 2.79–4.15 (mean PT Emax 41.0–62.7 s), compared with 1.41–1.74 (mean PT Emax 20.1–25.2 s) for warfarin alone. However, rivaroxaban had the smallest effect on INR at trough rivaroxaban concentrations. Neither rivaroxaban nor warfarin significantly affected maximum plasma concentrations of the other drug. Conclusions The combined pharmacodynamic effects during co-administration of rivaroxaban and warfarin were greater than additive, but the pharmacokinetics of both drugs were unaffected. Co-administration was well tolerated. When transitioning from rivaroxaban to warfarin, INR monitoring during co-administration should be performed at the trough rivaroxaban concentration to minimize the effect of rivaroxaban on INR. PMID:25475601

  6. Comparative efficacy trial of cupping and serkangabin versus conventional therapy of migraine headaches: A randomized, open-label, comparative efficacy trial

    Directory of Open Access Journals (Sweden)

    Mohammad Dehghani Firoozabadi

    2014-01-01

    Full Text Available Background: Migraine headaches are the most common acute and recurrent headaches. Current treatment of a migraine headache consists of multiple medications for control and prevention of recurrent attacks. Global emergence of alternative medicine led us to examine the efficacy of cupping therapy plus serkangabin syrup in the treatment of migraine headaches. Materials and Methods: This study was a randomized, controlled, open-label, comparative efficacy trial. We randomly assigned patients with migraine into cupping therapy plus serkangabin group (30 patients and conventional treatment group (30 patients. An investigator assessed the severity of headache, frequency of attacks in a week and duration of attacks per hour in 5 visits (at the end of 2 weeks, 1, 3 and 6 months. Generalized estimating equations approach was used to analyze repeated measures data to compare outcomes in both groups. Results: Average age for cupping therapy group and conventional treatment group were 31.7 (±7.6 and 32.6 (±12.7 years, respectively (P = 0.45. After treatment for 2 weeks; and 1, 3 and 6 months, severity of headache (P = 0.80, frequency of migraine attacks (P = 0.63 and duration of attacks per hours (P = 0.48 were similar in conventional and cupping groups but these symptoms were decreased in each group during the study (P < 0.001. Conclusion: There was no significant difference between cupping plus serkangabin therapy and conventional treatment in the treatment and prophylaxis of migraine. The alternative therapy may be used in cases of drug intolerance, no medication response, and in primary care.

  7. The effect of exercise on the absorption of inhaled human insulin in healthy volunteers

    DEFF Research Database (Denmark)

    Petersen, Astrid Heide; Kohler, Gerd; Korsatko, Stefan

    2008-01-01

    overall absorption. Aims To investigate the effect of moderate exercise on the absorption of inhaled insulin. Methods A single-centre, randomized, open-label, three-period cross-over trial was carried out in 12 nonsmoking healthy subjects. A dose of 3.5 mg inhaled human insulin was administered via...

  8. Pharmacokinetics of a telmisartan, amlodipine and ...

    African Journals Online (AJOL)

    Methods: This was a single-dose, randomized, open-label, replicate crossover study conducted in healthy male Korean ... FDCs containing the three drugs, and evaluate ... Subjects were forbidden from eating grape fruits ... who finished the study were used in the analysis ... regulations was conducted as an estimate of the.

  9. Quality assurance of rifampicin-containing fixed-drug combinations in South Africa: dosing implications.

    Science.gov (United States)

    Court, R; Chirehwa, M T; Wiesner, L; Wright, B; Smythe, W; Kramer, N; McIlleron, H

    2018-05-01

    Rifampicin (RMP) drives treatment response in drug-susceptible tuberculosis. Low RMP concentrations increase the risk of poor outcomes, and drug quality needs to be excluded as a contributor to low RMP exposure. We performed an open-label, three-way cross-over study of three licensed RMP-containing formulations widely used in South Africa to evaluate the bioavailability of RMP in a two-drug fixed-dose combination tablet (2FDC) and a four-drug FDC (4FDC) against a single-drug reference. RMP dosed at 600 mg was administered 2 weeks apart in random sequence. Plasma RMP concentrations were measured pre-dose and 1, 2, 3, 4, 6, 8 and 12 h post-dose. The area under the concentration-time curve (AUC0-12) of the FDCs was compared to the single drug reference. Simulations were used to predict the impact of our findings. Twenty healthy volunteers (median age 22.8 years, body mass index 24.2 kg/m2) completed the study. The AUC0-12 of the 4FDC/reference (geometric mean ratio [GMR] 78%, 90%CI 69-89) indicated an average 20% reduction in RMP bioavailability in the 4FDC. The 2FDC/reference (GMR 104%, 90%CI 97-111) was bioequivalent. Simulations suggested dose adjustments to compensate for the poor bioavailability of RMP with the 4FDC, and revised weight-band doses to prevent systematic underdosing of low-weight patients. Post-marketing surveillance of in vivo bioavailability of RMP and improved weight band-based dosing are recommended.

  10. Randomized comparative study of intravenous infusion of three different fixed doses of milrinone in pediatric patients with pulmonary hypertension undergoing open heart surgery.

    Science.gov (United States)

    Barnwal, Neeraj Kumar; Umbarkar, Sanjeeta Rajendra; Sarkar, Manjula Sudeep; Dias, Raylene J

    2017-01-01

    Pulmonary hypertension secondary to congenital heart disease is a common problem in pediatric patients presenting for open heart surgery. Milrinone has been shown to reduce pulmonary vascular resistance and pulmonary artery pressure in pediatric patients and neonates postcardiac surgery. We aimed to evaluate the postoperative outcome in such patients with three different fixed maintenance doses of milrinone. Patients were randomized into three groups. All patients received fixed bolus dose of milrinone 50 μg/kg on pump during rewarming. Following this, patients in low-dose group received infusion of milrinone at the rate of 0.375 μg/kg/min, medium-dose group received 0.5 μg/kg/min, and high-dose group received 0.75 μg/kg/min over 24 h. Heart rate, mean arterial pressure (MAP), mean airway pressure (MaP), oxygenation index (OI), and central venous pressure (CVP) were compared at baseline and 24 h postoperatively. Dose of inotropic requirement, duration of ventilatory support and Intensive Care Unit (ICU) stay were noted. MAP, MaP, OI, and CVP were comparable in all three groups postoperatively. All patients in the low-dose group required low inotropic support while 70% of patients in the high-dose group needed high inotropic support to manage episodes of hypotension (P = 0.000). Duration of ventilatory support and ICU stay in all three groups was comparable (P = 0.412, P = 0.165). Low-dose infusions while having a clinical impact were more beneficial in avoiding adverse events and decreasing inotropic requirement without affecting duration of ventilatory support and duration of ICU stay.

  11. Safety and pharmacodynamics of venetoclax (ABT-199) in a randomized single and multiple ascending dose study in women with systemic lupus erythematosus.

    Science.gov (United States)

    Lu, P; Fleischmann, R; Curtis, C; Ignatenko, S; Clarke, S H; Desai, M; Wong, S L; Grebe, K M; Black, K; Zeng, J; Stolzenbach, J; Medema, J K

    2018-02-01

    Objective The anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) may contribute to the pathogenesis of systemic lupus erythematosus. The safety, tolerability, and pharmacodynamics of the selective Bcl-2 inhibitor venetoclax (ABT-199) were assessed in women with systemic lupus erythematosus. Methods A phase 1, double-blind, randomized, placebo controlled study evaluated single ascending doses (10, 30, 90, 180, 300, and 500 mg) and multiple ascending doses (2 cycles; 30, 60, 120, 240, 400, and 600 mg for 1 week, and then 3 weeks off per cycle) of orally administered venetoclax. Eligible participants were aged 18-65 years with a diagnosis of systemic lupus erythematosus for 6 months or more receiving stable therapy for systemic lupus erythematosus (which could have included corticosteroids and/or stable antimalarials). Results All patients (48/48) completed the single ascending dose, 25 continued into the multiple ascending dose, and 44/50 completed the multiple ascending dose; two of the withdrawals (venetoclax 60 mg and 600 mg cohorts) were due to adverse events. Adverse event incidences were slightly higher in the venetoclax groups compared with the placebo groups, with no dose dependence. There were no serious adverse events with venetoclax. The most common adverse events were headache, nausea, and fatigue. Venetoclax 600 mg multiple ascending dose treatment depleted total lymphocytes and B cells by approximately 50% and 80%, respectively. Naive, switched memory, and memory B-cell subsets enriched in autoreactive B cells exhibited dose-dependent reduction of up to approximately 80%. There were no consistent or marked changes in neutrophils, natural killer cells, hemoglobin, or platelets. Conclusions Venetoclax was generally well tolerated in women with systemic lupus erythematosus and reduced total lymphocytes and disease-relevant subsets of antigen-experienced B cells. Registration ClinicalTrials.gov: NCT01686555.

  12. Effect of Steady-State Faldaprevir on Pharmacokinetics of Atorvastatin or Rosuvastatin in Healthy Volunteers: A Prospective Open-Label, Fixed-Sequence Crossover Study.

    Science.gov (United States)

    Huang, Fenglei; Marzin, Kristell; Koenen, Rüdiger; Kammerer, Klaus Peter; Strelkowa, Natalja; Elgadi, Mabrouk; Quinson, Anne-Marie; Haertter, Sebastian

    2017-10-01

    Faldaprevir (FDV) is a potent, orally administered inhibitor of hepatitis C virus protease. It inhibits multiple cytochrome P-450 enzymes and multiple membrane transporters. The objective of this study was to evaluate the effect of steady-state faldaprevir on the pharmacokinetics (PK) of a single dose of atorvastatin or rosuvastatin. In this single-center, open-label, fixed-sequence crossover study, 33 healthy adult male and female volunteers were given either atorvastatin 10 mg (n = 16) or rosuvastatin 10 mg (n = 17) on day 1. Subjects subsequently received 240 mg twice daily of faldaprevir (loading dose) on day 5, followed by 240 mg faldaprevir once daily from day 6 to day 10, with an additional single dose of atorvastatin (10 mg) or rosuvastatin (10 mg) given on day 10. PK samples for the statins were collected on days 1-3 and days 10-12. Concomitant administration with faldaprevir led to approximately 9-fold and 34-fold increases in AUC 0-∞ and C max , respectively, of atorvastatin and approximately 15-fold and 33-fold increases in AUC 0-∞ and C max , respectively, of rosuvastatin, compared with the statins given alone. Exposure to the major metabolites (ortho-hydroxyatorvastatin and N-desmethylrosuvastatin) was increased to a similar magnitude as that of the parent compounds. The marked drug-drug interaction observed is most likely related to the inhibitory effects of faldaprevir on transporters, particularly hepatic uptake transporters such as OTAP1B1 and OATP1B3. Given the significant increase in exposure to statins in healthy volunteers, coadministration of faldaprevir with statins should be avoided. © 2017, The American College of Clinical Pharmacology.

  13. Axitinib in combination with pembrolizumab in patients with advanced renal cell cancer: a non-randomised, open-label, dose-finding, and dose-expansion phase 1b trial.

    Science.gov (United States)

    Atkins, Michael B; Plimack, Elizabeth R; Puzanov, Igor; Fishman, Mayer N; McDermott, David F; Cho, Daniel C; Vaishampayan, Ulka; George, Saby; Olencki, Thomas E; Tarazi, Jamal C; Rosbrook, Brad; Fernandez, Kathrine C; Lechuga, Mariajose; Choueiri, Toni K

    2018-03-01

    Previous studies combining PD-1 checkpoint inhibitors with tyrosine kinase inhibitors of the VEGF pathway have been characterised by excess toxicity, precluding further development. We hypothesised that axitinib, a more selective VEGF inhibitor than others previously tested, could be combined safely with pembrolizumab (anti-PD-1) and yield antitumour activity in patients with treatment-naive advanced renal cell carcinoma. In this ongoing, open-label, phase 1b study, which was done at ten centres in the USA, we enrolled patients aged 18 years or older who had advanced renal cell carcinoma (predominantly clear cell subtype) with their primary tumour resected, and at least one measureable lesion, Eastern Cooperative Oncology Group performance status 0-1, controlled hypertension, and no previous systemic therapy for renal cell carcinoma. Eligible patients received axitinib plus pembrolizumab in a dose-finding phase to estimate the maximum tolerated dose, and additional patients were enrolled into a dose-expansion phase to further establish safety and determine preliminary efficacy. Axitinib 5 mg was administered orally twice per day with pembrolizumab 2 mg/kg given intravenously every 3 weeks. We assessed safety in all patients who received at least one dose of axitinib or pembrolizumab; antitumour activity was assessed in all patients who received study treatment and had an adequate baseline tumour assessment. The primary endpoint was investigator-assessed dose-limiting toxicity during the first two cycles (6 weeks) to estimate the maximum tolerated dose and recommended phase 2 dose. This study is registered with ClinicalTrials.gov, number NCT02133742. Between Sept 23, 2014, and March 25, 2015, we enrolled 11 patients with previously untreated advanced renal cell carcinoma to the dose-finding phase and between June 3, 2015, and Oct 13, 2015, we enrolled 41 patients to the dose-expansion phase. All 52 patients were analysed together. No unexpected toxicities were

  14. Clinical Efficacy Comparison of Saccharomyces boulardii and Yogurt Fluid in Acute Non-Bloody Diarrhea in Children: A Randomized, Controlled, Open Label Study

    Science.gov (United States)

    Eren, Makbule; Dinleyici, Ener C.; Vandenplas, Yvan

    2010-01-01

    The purpose of this trial is to evaluate the clinical efficacy and cost/effectiveness of Saccharomyces boulardii compared with yogurt fluid (YF) in acute non-bloody diarrhea in children. This randomized, prospective open-label clinical trial includes 55 children (36 boys, 19 girls; mean age 21.2 ± 28.2 months). Group A (N = 28) received lyophilized S. boulardii and group B (N = 27) received YF. The duration of diarrhea was shorter with S. boulardii but the hospital stay was reduced with YF, although these differences were not significant. However, diarrhea had resolved in significantly more children on day 3 in the S. boulardii group (48.5% versus 25.5%; P < 0.05). In outpatient cases, yogurt treatment was cheaper than S. boulardii whereas in hospitalized patients, treatment cost was similar. In conclusion, the effect of daily freshly prepared YF was comparable to S. boulardii in the treatment of acute non-bloody diarrhea in children. The duration of diarrhea was shorter in the S. boulardii group, expressed as a significantly higher number of patients with normal stools on day 3. PMID:20207879

  15. Clinical efficacy comparison of Saccharomyces boulardii and yogurt fluid in acute non-bloody diarrhea in children: a randomized, controlled, open label study.

    Science.gov (United States)

    Eren, Makbule; Dinleyici, Ener C; Vandenplas, Yvan

    2010-03-01

    The purpose of this trial is to evaluate the clinical efficacy and cost/effectiveness of Saccharomyces boulardii compared with yogurt fluid (YF) in acute non-bloody diarrhea in children. This randomized, prospective open-label clinical trial includes 55 children (36 boys, 19 girls; mean age 21.2 +/- 28.2 months). Group A (N = 28) received lyophilized S. boulardii and group B (N = 27) received YF. The duration of diarrhea was shorter with S. boulardii but the hospital stay was reduced with YF, although these differences were not significant. However, diarrhea had resolved in significantly more children on day 3 in the S. boulardii group (48.5% versus 25.5%; P boulardii whereas in hospitalized patients, treatment cost was similar. In conclusion, the effect of daily freshly prepared YF was comparable to S. boulardii in the treatment of acute non-bloody diarrhea in children. The duration of diarrhea was shorter in the S. boulardii group, expressed as a significantly higher number of patients with normal stools on day 3.

  16. Influence of random setup error on dose distribution

    International Nuclear Information System (INIS)

    Zhai Zhenyu

    2008-01-01

    Objective: To investigate the influence of random setup error on dose distribution in radiotherapy and determine the margin from ITV to PTV. Methods: A random sample approach was used to simulate the fields position in target coordinate system. Cumulative effect of random setup error was the sum of dose distributions of all individual treatment fractions. Study of 100 cumulative effects might get shift sizes of 90% dose point position. Margins from ITV to PTV caused by random setup error were chosen by 95% probability. Spearman's correlation was used to analyze the influence of each factor. Results: The average shift sizes of 90% dose point position was 0.62, 1.84, 3.13, 4.78, 6.34 and 8.03 mm if random setup error was 1,2,3,4,5 and 6 mm,respectively. Univariate analysis showed the size of margin was associated only by the size of random setup error. Conclusions: Margin of ITV to PTV is 1.2 times random setup error for head-and-neck cancer and 1.5 times for thoracic and abdominal cancer. Field size, energy and target depth, unlike random setup error, have no relation with the size of the margin. (authors)

  17. Multi-isocenter stereotactic radiotherapy: implications for target dose distributions of systematic and random localization errors

    International Nuclear Information System (INIS)

    Ebert, M.A.; Zavgorodni, S.F.; Kendrick, L.A.; Weston, S.; Harper, C.S.

    2001-01-01

    Purpose: This investigation examined the effect of alignment and localization errors on dose distributions in stereotactic radiotherapy (SRT) with arced circular fields. In particular, it was desired to determine the effect of systematic and random localization errors on multi-isocenter treatments. Methods and Materials: A research version of the FastPlan system from Surgical Navigation Technologies was used to generate a series of SRT plans of varying complexity. These plans were used to examine the influence of random setup errors by recalculating dose distributions with successive setup errors convolved into the off-axis ratio data tables used in the dose calculation. The influence of systematic errors was investigated by displacing isocenters from their planned positions. Results: For single-isocenter plans, it is found that the influences of setup error are strongly dependent on the size of the target volume, with minimum doses decreasing most significantly with increasing random and systematic alignment error. For multi-isocenter plans, similar variations in target dose are encountered, with this result benefiting from the conventional method of prescribing to a lower isodose value for multi-isocenter treatments relative to single-isocenter treatments. Conclusions: It is recommended that the systematic errors associated with target localization in SRT be tracked via a thorough quality assurance program, and that random setup errors be minimized by use of a sufficiently robust relocation system. These errors should also be accounted for by incorporating corrections into the treatment planning algorithm or, alternatively, by inclusion of sufficient margins in target definition

  18. Long-term safety and effectiveness of once-daily, single-entity, extended-release hydrocodone over 76 weeks of an open-label study in patients with chronic noncancer and nonneuropathic pain.

    Science.gov (United States)

    Taber, Louise; Lynch, Shau Yu; He, Ellie; Ripa, Steven R

    2016-01-01

    To evaluate long-term use of Hysingla(®) ER (HYD), a single-entity, extended-release, once-daily hydrocodone bitartrate tablet with abuse-deterrent properties in patients with moderate-to-severe chronic noncancer and nonneuropathic pain. This open-label study consisted of a dose-titration period (up to 45 days), a 52-week maintenance period and a 24-week extension period. Opioid-naïve or opioid-experienced patients with controlled or uncontrolled chronic pain conditions were treated with HYD 20-120 mg daily. Supplemental nonopioid and short-acting opioid analgesics were permitted. This paper presents the results of 106 patients who continued HYD treatment for up to 76 weeks. Primary safety measures included the incidence of adverse events, as well as audiologic, clinical laboratory and electrocardiogram measurements. Effectiveness was measured by the change between baseline and the overall 76-week treatment period in "average pain over the last 24 h" (0 = no pain, 10 = pain as bad as you can imagine), Brief Pain Inventory-Short Form survey, Medical Outcomes Study 36-Item Short Form Health Survey, Medical Outcomes Study Sleep Scale-Revised and concomitant nonstudy opioid analgesic use. Among 410 patients who completed the maintenance period, 106 continued into the extension. Of these, 83 (78%) completed the entire 76-week treatment period. Treatment-emergent adverse events were typical of those observed with μ-opioid agonists. No study drug abuse or diversion was reported. Clinically important analgesia and functional improvement were achieved during the dose-titration period and were maintained in most patients throughout 76 weeks without the need for continued HYD dose increases or changes in concomitant nonstudy opioid analgesics. The mean pain score was 6.1 at baseline, 3.8 at the end of the dose titration period and 3.8 through 76 weeks. HYD was generally well tolerated. No unexpected safety concerns emerged. Pain control was sustained throughout 76 weeks of

  19. Validation of a label dosimeter with regard to dose assurance in critical applications as quarantine control

    Energy Technology Data Exchange (ETDEWEB)

    Ehlermann, D A.E. [Institute of Process Engineering, Federal Research Centre for Nutrition, Karlsruhe (Germany)

    1999-03-01

    A `label dosimeter` (dose-threshold indicator) for dose ranges of insect disinfestation became commercially available only recently. It was studied for dosimetric (metrological) properties elsewhere. The fundamental problem of its application in practice is the relation between the dose observed at a reference position and the critical minimum dose achieved in a consignment. For this reason several irradiation geometries (relations between the arrangement of the goods during irradiation and the type of the radiation source, gamma, electrons, X-rays) were studied. The observed dose distributions revealed the difficulty that for any such geometry a `label dosimeter` with a specific but differing threshold dose-value must be utilized in order to guarantee the adherence to the required minimum dose value. The `label dosimeter` must be placed at a position where the minimum dose is likely to occur. In situations where the position of the minimum dose is not accessible extrapolation from the dose observed at a reference position is less reliable. (author) 6 refs, 5 figs, 1 tab

  20. Validation of a label dosimeter with regard to dose assurance in critical applications as quarantine control

    International Nuclear Information System (INIS)

    Ehlermann, D.A.E.

    1999-01-01

    A 'label dosimeter' (dose-threshold indicator) for dose ranges of insect disinfestation became commercially available only recently. It was studied for dosimetric (metrological) properties elsewhere. The fundamental problem of its application in practice is the relation between the dose observed at a reference position and the critical minimum dose achieved in a consignment. For this reason several irradiation geometries (relations between the arrangement of the goods during irradiation and the type of the radiation source, gamma, electrons, X-rays) were studied. The observed dose distributions revealed the difficulty that for any such geometry a 'label dosimeter' with a specific but differing threshold dose-value must be utilized in order to guarantee the adherence to the required minimum dose value. The 'label dosimeter' must be placed at a position where the minimum dose is likely to occur. In situations where the position of the minimum dose is not accessible extrapolation from the dose observed at a reference position is less reliable. (author)

  1. Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma: a multicentre, single-group, open-label, phase 2 trial.

    Science.gov (United States)

    Kaufman, Howard L; Russell, Jeffery; Hamid, Omid; Bhatia, Shailender; Terheyden, Patrick; D'Angelo, Sandra P; Shih, Kent C; Lebbé, Céleste; Linette, Gerald P; Milella, Michele; Brownell, Isaac; Lewis, Karl D; Lorch, Jochen H; Chin, Kevin; Mahnke, Lisa; von Heydebreck, Anja; Cuillerot, Jean-Marie; Nghiem, Paul

    2016-10-01

    Merkel cell carcinoma is a rare, aggressive skin cancer with poor prognosis in patients with advanced disease. Current standard care uses various cytotoxic chemotherapy regimens, but responses are seldom durable. Tumour oncogenesis is linked to Merkel cell polyomavirus integration and ultraviolet-radiation-induced mutations, providing rationale for treatment with immunotherapy antibodies that target the PD-L1/PD-1 pathway. We assessed treatment with avelumab, an anti-PD-L1 monoclonal antibody, in patients with stage IV Merkel cell carcinoma that had progressed after cytotoxic chemotherapy. In this multicentre, international, prospective, single-group, open-label, phase 2 trial, patients with stage IV chemotherapy-refractory, histologically confirmed Merkel cell carcinoma (aged ≥18 years) were enrolled from 35 cancer treatment centres and academic hospitals in North America, Europe, Australia, and Asia. Key eligibility criteria were an ECOG performance status of 0 or 1, measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, adequate haematological, hepatic, and renal function, and immune-competent status (patients with HIV, immunosuppression, haematological malignancies, and previous organ transplantation were excluded). Patient selection was not based on PD-L1 expression or Merkel cell polyomavirus status. Collection of biopsy material or use of archival tissue for these assessments was mandatory. Avelumab was given intravenously at a dose of 10 mg/kg every 2 weeks. The primary endpoint was confirmed objective response (complete response or partial response) assessed according to RECIST version 1.1 by an independent review committee. Safety and clinical activity were assessed in all patients who received at least one dose of study drug (the modified intention-to-treat population). This trial is registered with ClinicalTrials.gov as NCT02155647. Between July 25, 2014, and Sept 3, 2015, 88 patients were enrolled and received at

  2. Clinical Efficacy and Safety of Oral Qing-Dai in Patients with Ulcerative Colitis: A Single-Center Open-Label Prospective Study.

    Science.gov (United States)

    Sugimoto, Shinya; Naganuma, Makoto; Kiyohara, Hiroki; Arai, Mari; Ono, Keiko; Mori, Kiyoto; Saigusa, Keiichiro; Nanki, Kosaku; Takeshita, Kozue; Takeshita, Tatsuya; Mutaguchi, Makoto; Mizuno, Shinta; Bessho, Rieko; Nakazato, Yoshihiro; Hisamatsu, Tadakazu; Inoue, Nagamu; Ogata, Haruhiko; Iwao, Yasushi; Kanai, Takanori

    2016-01-01

    Chinese herbal medicine Qing-Dai (also known as indigo naturalis) has been used to treat various inflammatory conditions. However, not much has been studied about the use of oral Qing-Dai in the treatment for ulcerative colitis (UC) patients. Studies exploring alternative treatments for UC are of considerable interest. In this study, we aimed at prospectively evaluating the safety and efficacy of Qing-Dai for UC patients. The open-label, prospective pilot study was conducted at Keio University Hospital. A total of 20 patients with moderate UC activity were enrolled. Oral Qing-Dai in capsule form was taken twice a day (daily dose, 2 g) for 8 weeks. At week 8, the rates of clinical response, clinical remission, and mucosal healing were 72, 33, and 61%, respectively. The clinical and endoscopic scores, CRP levels, and fecal occult blood results were also significantly improved. We observed 2 patients with mild liver dysfunction; 1 patient discontinued due to infectious colitis and 1 patient discontinued due to mild nausea. This is the first prospective study indicating that oral Qing-Dai is effective for inducing remission in patients with moderate UC activity and can be tolerated. Thus, Qing-Dai may be considered an alternative treatment for patients, although further investigation is warranted. © 2016 S. Karger AG, Basel.

  3. Mobility and height detection of particle labels in an optical evanescent wave biosensor with single-label resolution

    NARCIS (Netherlands)

    van Ommering, K.; Somers, P.A.; Koets, M.; Schleipen, J.J.H.B.; IJzendoorn, van L.J.; Prins, M.W.J.

    2010-01-01

    Particle labels are used in biosensors to detect the presence and concentration of analyte molecules. In this paper we demonstrate an optical technique to measure the mobility and height of bound particle labels on a biosensor surface with single-label resolution. The technique is based on the

  4. Randomized comparative study of intravenous infusion of three different fixed doses of milrinone in pediatric patients with pulmonary hypertension undergoing open heart surgery

    Directory of Open Access Journals (Sweden)

    Neeraj Kumar Barnwal

    2017-01-01

    Full Text Available Background: Pulmonary hypertension secondary to congenital heart disease is a common problem in pediatric patients presenting for open heart surgery. Milrinone has been shown to reduce pulmonary vascular resistance and pulmonary artery pressure in pediatric patients and neonates postcardiac surgery. We aimed to evaluate the postoperative outcome in such patients with three different fixed maintenance doses of milrinone. Methodology: Patients were randomized into three groups. All patients received fixed bolus dose of milrinone 50 μg/kg on pump during rewarming. Following this, patients in low-dose group received infusion of milrinone at the rate of 0.375 μg/kg/min, medium-dose group received 0.5 μg/kg/min, and high-dose group received 0.75 μg/kg/min over 24 h. Heart rate, mean arterial pressure (MAP, mean airway pressure (MaP, oxygenation index (OI, and central venous pressure (CVP were compared at baseline and 24 h postoperatively. Dose of inotropic requirement, duration of ventilatory support and Intensive Care Unit (ICU stay were noted. Results: MAP, MaP, OI, and CVP were comparable in all three groups postoperatively. All patients in the low-dose group required low inotropic support while 70% of patients in the high-dose group needed high inotropic support to manage episodes of hypotension (P = 0.000. Duration of ventilatory support and ICU stay in all three groups was comparable (P = 0.412, P = 0.165. Conclusion: Low-dose infusions while having a clinical impact were more beneficial in avoiding adverse events and decreasing inotropic requirement without affecting duration of ventilatory support and duration of ICU stay.

  5. Effect of benzalkonium chloride?free travoprost on intraocular pressure and ocular surface symptoms in patients with glaucoma previously on latanoprost: an open-label study

    OpenAIRE

    Lopes, Joao F.; Hubatsch, Douglas A.; Amaris, Patricia

    2015-01-01

    Background Prostaglandin analogs reduce intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension; however, these medications may affect the ocular surface and elicit ocular discomfort when preserved with benzalkonium chloride (BAK). Methods This was an open-label, single-arm study conducted in Latin America from February 2012 to May 2013. Patients with open-angle glaucoma or ocular hypertension who were intolerant of latanoprost 0.005?% were transitioned to recei...

  6. Prospective, randomized, open-label, blinded-endpoint (PROBE) designed trials yield the same results as double-blind, placebo-controlled trials with respect to ABPM measurements.

    Science.gov (United States)

    Smith, David H; Neutel, Joel M; Lacourcière, Yves; Kempthorne-Rawson, Joan

    2003-07-01

    This meta-analysis aimed to determine whether ambulatory blood pressure monitoring (ABPM) results from double-blind, placebo-controlled (DBPC) and prospective, randomized, open-label, blinded-endpoint (PROBE) hypertension trials are statistically comparable. Two DBPC and three PROBE parallel-group studies were selected from an angiotensin II receptor blocker clinical programme. These were fixed-dose studies involving similar mild to moderate hypertensive patient populations. All used SpaceLabs 90207 ABPM devices, and each comprised a 4-week placebo period and a 4-8-week treatment period. Data from patients receiving telmisartan 80 mg were used to compare the results of DBPC (126 patients) and PROBE (734 patients) trials. The analysis had approximately 87% power to show equivalence between the two design types in terms of ruling out differences of >or= 3 mmHg in SBP and >or= 2 mmHg in DBP. Office blood pressure was also compared. The change from baseline in mean 24-h ambulatory SBP was -12.2 mmHg in DBPC trials and -12.3 mmHg in PROBE trials, a rounded difference of 0.2 mmHg [95% confidence interval (CI): -1.8, 2.1]. The change from baseline in mean 24-h ambulatory DBP was -7.7 mmHg in DBPC trials versus -7.9 mmHg in PROBE trials, a difference of 0.2 mmHg (95% CI: -1.1, 1.5). Ambulatory pulse pressure results were identical. Thus, changes in mean 24-h ambulatory blood pressure from the DBPC and PROBE trials in this meta-analysis are statistically equivalent in terms of ruling out a difference of >or= 3 mmHg in SBP and >or= 2 mmHg in DBP. This supports the validity of the PROBE design in assessing antihypertensive efficacy based on blinded ABPM measurements.

  7. Single and repeated dose pharmacokinetics of dexketoprofen trometamol in patients with impaired liver function.

    Science.gov (United States)

    Valles, J; Artigas, R; Bertolotti, M; Crea, A; Muller, F; Paredes, I; Capriati, A

    2006-06-01

    Dexketoprofen trometamol, a high water-soluble salt of the active enantiomer of rac-ketoprofen, is a nonsteroidal antiinflammatory drug (NSAID) used for pain relief. This study compared the pharmacokinetics of dexketoprofen in patients with impaired liver function and normal subjects following single and repeated oral dosing. Subjects with normal liver function (n = 6) and with Child-Pugh A (n = 7) or Child-Pugh B (n = 5) hepatic impairment scores completed this open-label and parallel study. They received 25 mg dexketoprofen (equivalent to 37 mg of its tromethamine salt) as a single (day 1) and a 3-day repeated dose (1 dose every 8 hours for a total of 10 doses). Dexketoprofen concentrations were determined in plasma and urine by reverse-phase high performance liquid chromatography (HPLC). Model-independent pharmacokinetic parameters were obtained. All subjects completed the study. No serious adverse events were recorded. Following the single dose, mean (+/- SEM) Cmax were 3027.7 +/- 429.3 ng/ml (healthy subjects), 2856.3 +/- 340.3 ng/ml (Child-Pugh A) and 1937.2 +/- 328.0 ng/ml (Child-Pugh B). Median tmax were 0.49 h (0.33-0.68) h, 0.50 h (0.33-0.67) h and 0.67 h (0.33-1.50) h. AUC0-x averaged 3778.0 +/- 439.0 ng.h/ml, 4890.4 +/- 539.1 ng.h/ml and 3985.0 +/- 712.0 ng.h/ml. Mean CL/F were 101.1 +/- 11.3 ml/h/kg, 73.3 +/- 9.9 ml/h/kg and 88.8 +/- 15.5 ml/h/kg and V/F averaged 0.192 +/- 0.018 l/kg, 0.162 +/- 0.006 l/kg and 0.214 +/- 0.044 l/kg. Following the repeated administration, similar results were obtained showing no drug accumulation. As related to the administered dose, median excretions of unchanged and conjugated dexketoprofen in urine were 2.1% and 67.1% in healthy subjects, 2.8% and 60.9% in Child-Pugh A subjects and 4.4% and 47.7% in Child-Pugh B volunteers. A trend towards a reduced urinary excretion of conjugated dexketoprofen in hepatic patients, more evident in the Child-Pugh B than in the Child-Pugh A groups, was observed when compared with healthy

  8. A study of dose-proportionality in the pharmacokinetics of the oral direct renin inhibitor aliskiren in healthy subjects.

    Science.gov (United States)

    Limoges, D; Dieterich, H A; Yeh, C-M; Vaidyanathan, S; Howard, D; Dole, W P

    2008-05-01

    To evaluate the dose-proportionality of the pharmacokinetics of aliskiren, the first in a new class of orally active direct renin inhibitors approved for the treatment of hypertension. This was an open-label, single-center, single-dose, randomized, 4-period crossover study. Following a 21-day screening period, 32 healthy male or female subjects (ages 18 - 45 years) were randomized to 1 of 4 aliskiren dosing sequence groups (8 subjects per group): 75, 150, 300 and 600 mg. Blood samples were obtained for determination of plasma aliskiren concentrations (HPLC/MS/MS) for 96 h post dose. Log-transformed pharmacokinetic parameters AUC and C(max) were analyzed to determine dose-proportionality using the power model, parameter = A*(Dose)(beta), where A = intercept and beta = dose-proportionality coefficient. The predefined dose-proportionality criteria over the dose range 75 â 600 mg were 90% confidence intervals (CI) for beta contained within the range 0.89 - 1.11. AUC and Cmax values increased with increasing doses of aliskiren. Both AUC and C(max) were associated with high variability (coefficient of variation 55 - 64% for AUC and 59 - 117% for C(max)). The estimated proportionality coefficients (beta) for AUC(0-infiniti), AUC(0-t) and C(max) were 1.18 (90% CI 1.10, 1.25), 1.29 (90% CI 1.22, 1.36) and 1.42 (90% CI 1.31, 1.52), respectively. Dose-proportionality was, therefore, not demonstrated across the entire 8-fold dose range. For the clinical dose range of 150 â 300 mg, increases of 2.3- and 2.6-fold were observed for AUC and C(max), respectively. All doses of aliskiren were well tolerated. Exposure to aliskiren was greater than proportional over the dose range of 75 - 600 mg. Over the therapeutic dose range of 150 â 300 mg approved for the treatment of hypertension, AUC and Cmax increased by 2.3- and 2.6-fold, respectively. The pharmacokinetics of aliskiren show relatively high intersubject variability.

  9. A 6-week, multicenter, randomized, double-masked, parallel-group study comparing travoprost 0.004% to latanoprost 0.005% followed by 6-week, open-label treatment with travoprost 0.004%.

    Science.gov (United States)

    Maul, Eugenio; Carrasco, Félix Gil; Costa, Vital Paulino; Casiraghi, Javier F; Vargas, Enrique; Sarmina, Judith S; Mayol, Renato

    2007-09-01

    The aim of this study was to compare the tolerability and efficacy of once-daily travoprost 0.004% versus latanoprost 0.005% for 6 weeks followed by 6 weeks of once-daily travoprost 0.004% in decreasing intraocular pressure (IOP) in patients with open-angle glaucoma (OAG) or ocular hypertension (OH). This multicenter, randomized, doublemasked, active-controlled, parallel-group trial was conducted at 32 centers across Latin America. Patients aged > or =18 years with OAG or OH were randomly assigned to receive topical travoprost 0.004% or latanoprost 0.005% 1 drop QD (9 PM) for 6 weeks (masked phase). At 6 weeks, all patients were assigned to receive open-label travoprost 0.004% 1 drop QD (9 PM) for 6 additional weeks (open-label phase). Study visits were scheduled at weeks 1, 2, 4, 6, 8, and 12. At each study visit, IOP was measured at 5 PM (+/-1 hour; approximately 20 hours after study drug administration). IOP changes from baseline were combined (pooled) from the 1-, 2-, 4-, and 6-week data to provide a comparison between the 2 treatment groups. Ocular adverse events (AEs) were monitored using slit-lamp examination. A total of 302 patients were enrolled (travoprost group, 155 patients; latanoprost group, 147 patients). The mean (SD) age of the travoprost group was 61.9 (10.6) years; 60.6% were female; and 47.1% were white. The mean (SD) age of the latanoprost group was 60.5 (12.4) years; 62.6% were female; and 49.0% were white. Mean IOP values were not significantly different between the travoprost and latanoprost groups at baseline (24.7 vs 24.2 mm Hg) or 6 weeks; however, the between-group difference in reductions from baseline in pooled IOP during the masked phase of the study was statistically significant (-8.3 vs -7.5 mm Hg; P = 0.009). At weeks 6 and 12, mean lOP levels were 16.1 and 16.2 mm Hg, respectively, in the travoprost group and 16.4 and 16.1 mm Hg in the group that was switched from latanoprost to travoprost (all, P = NS). The most common ocular AEs

  10. LDL-cholesterol lowering effect of a new dietary supplement: an open label, controlled, randomized, cross-over clinical trial in patients with mild-to-moderate hypercholesterolemia.

    Science.gov (United States)

    Magno, S; Ceccarini, G; Pelosini, C; Jaccheri, R; Vitti, J; Fierabracci, P; Salvetti, G; Airoldi, G; Minale, M; Saponati, G; Santini, F

    2018-05-24

    Hypercholesterolemia is a major risk factor for cardiovascular disorders and requires specific intervention through an adequate lifestyle (diet and physical exercise) and, if necessary, an appropriate drug treatment. Lipid-lowering drugs, although generally efficacious, may sometimes cause adverse events. A growing attention has been devoted to the correction of dyslipidemias through the use of dietary supplements. The aim of this study was to assess the lipid-lowering activity and safety of a dietary supplement containing monacolin K, L-arginine, coenzyme Q10 and ascorbic acid, named Argicolina (A), compared to a commercially available product containing monacolin K and coenzyme Q10, Normolip 5 (N). This was a single center, controlled, randomized, open-label, cross-over clinical study enrolling 20 Caucasian outpatients aged 18-75 years with serum LDL-C between 130 and 180 mg/dL. Patients assumed two different dietary supplements (A and N) both containing monacolin K 10 mg for 8 weeks each, separated by a 4-week wash-out period. Evaluated parameters were: Total cholesterol (Tot-C), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides (TG), fasting blood glucose, aspartate aminotransferase, alanine aminotransferase, creatinekinase, gamma-glutamyl-transpeptidase, brachial arterial pressure and heart rate, measured at the start and at the end of each treatment period. Safety was monitored through the study. LDL-C decreased by 23.3% during treatment with N (p ascorbic acid also produces a significant reduction of triglycerides without significant effects on HDL. ClinicalTrials.gov ID: NCT03425630 .

  11. An open-label, two-period comparative study on pharmacokinetics and safety of a combined ethinylestradiol/gestodene transdermal contraceptive patch

    Directory of Open Access Journals (Sweden)

    Zhang C

    2017-03-01

    Full Text Available Chao Zhang,1 Haiyan Li,2 Xin Xiong,1 Suodi Zhai,1 Yudong Wei,2 Shuang Zhang,2 Yuanyuan Zhang,1 Lin Xu,2 Li Liu1 1Department of Pharmacy, 2Institute of Clinical Trial, Peking University Third Hospital, Beijing, People’s Republic of China Abstract: We investigated the pharmacokinetics and safety profiles of a newly developed combined ethinylestradiol (EE/gestodene (GSD transdermal contraceptive patch after a single-dose administration and compared with the market available tablet formulation in healthy adult subjects. An open-label, two-period comparative study was conducted in 12 healthy women volunteers. A single dose of the study combined EE/GE transdermal contraceptive patch and oral tablet (Milunet® were administered. Blood samples at different time points after dose were collected, and concentrations were analyzed. A reliable, highly sensitive and accurate high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC/MS/MS assay method was developed in this study to determine the plasma concentrations of EE and GSD. Compared to the tablet, the study patch had a significantly decreased maximum plasma concentration (Cmax, extended time to reach the Cmax and half-life, as well as increased clearance and apparent volume of distribution. The half-lives of EE and GSD of the patch were 3.3 and 2.2 times, respectively, than the half-life of the tablet. The areas under the plasma concentration–time curve (AUCs of EE and GSD of the patch were 8.0 and 16.2 times, respectively, than the AUC of the tablet. No severe adverse event was observed during the whole study, and the general safety was acceptable. In conclusion, compared to the oral tablet Milunet, the study contraceptive patch was well tolerated and showed potent drug exposure, significant extended half-life and stable drug concentrations. Keywords: pharmacokinetics, safety, ethinylestradiol/gestodene, transdermal contraceptive patch

  12. Effect of Amygdalus scoparia kernel oil consumption on lipid profile of the patients with dyslipidemia: a randomized, open-label controlled clinical trial.

    Science.gov (United States)

    Zibaeenezhad, Mohammad Javad; Shahamat, Maryam; Mosavat, Seyed Hamdollah; Attar, Armin; Bahramali, Ehsan

    2017-10-03

    Amygdalus scoparia kernel (ASK) oil is traditionally used for Hyperlipidemia. Compared to olive oil, it has higher proportion of unsaturated to saturated fatty acid besides exhibiting higher index of oxidative stability. The lipid-lowering effects of ASK oil however, has not been investigated yet. This study is the first one to evaluate such effects in patients with dyslipidemia. Serum triglyceride levels significantly decreased in the intervention compared to control group (24.80 ± 51.70 vs 3.13 ± 44.80, p -value = 0.03). Serum total cholesterol, LDL and HDL cholesterol levels did not change significantly ( p = 0.28 and p = 0.68 and p = 0.10 respectively). In a double arm, open-label, randomized controlled trial,101 hyperlipidemic patients were recruited. The designation of hyperlipidemia was upon meeting either of the three criteria: having serum low-density lipoprotein (LDL) cholesterol level 130-190 (mg/dl), serum triglyceride level 150-400 (mg/dl), and serum high-density lipoprotein (HDL) cholesterol level less than 50 (mg/dl) for women and 40 (mg/dl) for men. Patients who have ever been prescribed with an antihyperlipidemic medication were excluded. They were randomly assigned to intervention group, receiving the ASK oil, for 60 days and control group. Serum lipid measurements were repeated at the end of the intervention period. ASK oil supplementation may have a positive effect in reducing serum triglyceride level in patients with dyslipidemia without significant effect on serum cholesterol levels.

  13. Single-dose and multiple-dose pharmacokinetics and dose proportionality of intravenous and intramuscular HPβCD-diclofenac (Dyloject) compared with other diclofenac formulations.

    Science.gov (United States)

    Mermelstein, Fred; Hamilton, Douglas A; Wright, Curtis; Lacouture, Peter G; Ramaiya, Atulkumar; Carr, Daniel B

    2013-10-01

    To evaluate single- and repeated-dose pharmacokinetics (PK) and dose proportionality of hydroxypropyl-β-cyclodextrin (HPβCD)-diclofenac compared with Voltarol after intravenous (IV) and intramuscular (IM) administration. Study 1: Single-dose randomized four-way crossover study. Study 2: Multiple-dose randomized three-way crossover study. Clinical research center. Healthy adult volunteers. Study 1: Subjects received HPβCD-diclofenac and Voltarol, IV and IM, with a 5-day washout between treatment periods. Study 2: Subjects received two doses of IV HPβCD-diclofenac and oral Cataflam once every 6 hours for four doses with a 48-hour washout period between treatment periods. Study 1: IV HPβCD-diclofenac had a higher peak plasma concentration (Cmax ) and earlier time to reach maximum plasma concentration (Tmax ), but equivalent plasma exposure (area under the curve from time zero to t [AUC0-t ]) to IV Voltarol. The geometric mean ratio of HPβCD-diclofenac (IV) to Voltarol (IV) for AUC0-t was 106.27%. The geometric mean ratio of HPβCD-diclofenac (IM) to Voltarol (IM) for AUC0-t was 110.91%. The geometric mean ratio of HPβCD-diclofenac (IV) to HPβCD-diclofenac (IM) for AUC0-t was 101.25%. The geometric mean ratio of HPβCD-diclofenac (IM) to Voltarol (IV) for AUC0-t was 104.96%. Study 2: Cmax for diclofenac was 2904 and 6031 ng/ml after the first IV dose of 18.75 and 37.5 mg HPβCD-diclofenac, respectively, and was 3090 and 5617 ng/ml after the fourth dose, indicating no accumulation. Plasma exposures to 18.75 mg (866 ng·hour/ml) and 37.5 mg (1843 ng·hour/ml) IV HPβCD-diclofenac bracketed that of oral Cataflam 50 mg (1473 ng·hour/ml). Study 1: Bioavailability in terms of AUC after IV administration was equivalent for HPβCD-diclofenac compared with Voltarol and after IM administration of HPβCD-diclofenac and Voltarol. Bioavailability in terms of AUC after IM administration of HPβCD-diclofenac was equivalent to IV administration of HP

  14. Impact of prior treatment and depth of response on survival in MM-003, a randomized phase 3 study comparing pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone in relapsed/refractory multiple myeloma

    Science.gov (United States)

    San Miguel, Jesus F.; Weisel, Katja C.; Song, Kevin W.; Delforge, Michel; Karlin, Lionel; Goldschmidt, Hartmut; Moreau, Philippe; Banos, Anne; Oriol, Albert; Garderet, Laurent; Cavo, Michele; Ivanova, Valentina; Alegre, Adrian; Martinez-Lopez, Joaquin; Chen, Christine; Renner, Christoph; Bahlis, Nizar Jacques; Yu, Xin; Teasdale, Terri; Sternas, Lars; Jacques, Christian; Zaki, Mohamed H.; Dimopoulos, Meletios A.

    2015-01-01

    Pomalidomide is a distinct oral IMiD® immunomodulatory agent with direct antimyeloma, stromal-support inhibitory, and immunomodulatory effects. The pivotal, multicenter, open-label, randomized phase 3 trial MM-003 compared pomalidomide + low-dose dexamethasone vs high-dose dexamethasone in 455 patients with refractory or relapsed and refractory multiple myeloma after failure of bortezomib and lenalidomide treatment. Initial results demonstrated significantly longer progression-free survival and overall survival with an acceptable tolerability profile for pomalidomide + low-dose dexamethasone vs high-dose dexamethasone. This secondary analysis describes patient outcomes by treatment history and depth of response. Pomalidomide + low-dose dexamethasone significantly prolonged progression-free survival and favored overall survival vs high-dose dexamethasone for all subgroups analyzed, regardless of prior treatments or refractory status. Both univariate and multivariate analyses showed that no variable relating to either the number (≤ or > 3) or type of prior treatment was a significant predictor of progression-free survival or overall survival. No cross-resistance with prior lenalidomide or thalidomide treatment was observed. Patients achieving a minimal response or better to pomalidomide + low-dose dexamethasone treatment experienced a survival benefit, which was even higher in those achieving at least a partial response (17.2 and 19.9 months, respectively, as compared with 7.5 months for patients with less than minimal response). These data suggest that pomalidomide + low-dose dexamethasone should be considered a standard of care in patients with refractory or relapsed and refractory multiple myeloma regardless of prior treatment. ClinicalTrials.gov: NCT01311687; EudraCT: 2010-019820-30. PMID:26160879

  15. Efficacy of two different doses of rabbit anti-T-lymphocyte globulin to prevent graft-versus-host disease in children with haematological malignancies transplanted from an unrelated donor: a multicentre, randomised, open-label, phase 3 trial.

    Science.gov (United States)

    Locatelli, Franco; Bernardo, Maria Ester; Bertaina, Alice; Rognoni, Carla; Comoli, Patrizia; Rovelli, Attilio; Pession, Andrea; Fagioli, Franca; Favre, Claudio; Lanino, Edoardo; Giorgiani, Giovanna; Merli, Pietro; Pagliara, Daria; Prete, Arcangelo; Zecca, Marco

    2017-08-01

    Although rabbit anti-T-lymphocyte globulin (ATLG) is largely used for the prevention of immune-mediated complications in patients given allogeneic haemopoietic stem-cell transplantation (HSCT) from an unrelated donor, the optimum dose of this drug in children is still undefined. We aimed to test whether a higher dose of ATLG was superior to a lower dose for prevention of grade II-IV acute graft-versus-host disease (GVHD). We conducted a multicentre, randomised, open-label, phase 3 trial in seven Italian centres comparing two different doses of ATLG (30 mg/kg vs 15 mg/kg, given intravenously over 3 days, from day -4 to -2) in children (aged 0-18 years) with haematological malignancies transplanted from an unrelated donor, selected using high-resolution typing for HLA-class I/II loci. All patients received a myeloablative regimen and cyclosporine-A plus short-term methotrexate as post-transplantation GVHD prophylaxis. Patients were randomly assigned (1:1) to either of the two groups and were stratified by the degree of HLA-compatibility with their donor, the source of haemopoietic stem cells used (bone marrow vs peripheral blood stem cells), and the disease risk category. The randomisation was open label; all investigators were aware of the treatment allocation. The primary endpoint of the study was 100-day cumulative incidence of grade II-IV acute GVHD. Statistical analyses were done according to the per-protocol principle. Other outcomes included cumulative incidence of chronic GVHD, non-relapse mortality, disease recurrence, and probability of overall survival and event-free survival. This study was registered with ClinicalTrials.gov, number NCT00934557. Between Jan 15, 2008, and Sept 25, 2012, 89 patients were randomly assigned to the 30 mg/kg ATLG group and 91 to the 15 mg/kg ATLG group; 84 patients in the 30 mg/kg ATLG group and 88 in the 15 mg/kg ATLG group were included in the analysis. The median follow-up for the whole study population was 3·4 years (IQR 1

  16. An open-label naturalistic pilot study of acamprosate in youth with autistic disorder.

    Science.gov (United States)

    Erickson, Craig A; Early, Maureen; Stigler, Kimberly A; Wink, Logan K; Mullett, Jennifer E; McDougle, Christopher J

    2011-12-01

    To date, placebo-controlled drug trials targeting the core social impairment of autistic disorder (autism) have had uniformly negative results. Given this, the search for new potentially novel agents targeting the core social impairment of autism continues. Acamprosate is U.S. Food and Drug Administration-approved drug to treat alcohol dependence. The drug likely impacts both gamma-aminobutyric acid and glutamate neurotransmission. This study describes our initial open-label experience with acamprosate targeting social impairment in youth with autism. In this naturalistic report, five of six youth (mean age, 9.5 years) were judged treatment responders to acamprosate (mean dose 1,110 mg/day) over 10 to 30 weeks (mean duration, 20 weeks) of treatment. Acamprosate was well tolerated with only mild gastrointestinal adverse effects noted in three (50%) subjects.

  17. A single-dose, randomized, cross-over, two-way, open-label study for comparing the absorption of boswellic acids and its lecithin formulation.

    Science.gov (United States)

    Riva, Antonella; Morazzoni, Paolo; Artaria, Christian; Allegrini, Pietro; Meins, Jürgen; Savio, Daniele; Appendino, Giovanni; Schubert-Zsilavecz, Manfred; Abdel-Tawab, Mona

    2016-11-15

    The oral administration of the gum resin extracts of Indian frankincense (Boswellia serrata Roxb. ex Colebr) results in very low plasma concentrations of boswellic acids (BAs), being far below the pharmacologically active concentrations required in vitro for anti-inflammatory activity. For that reason the use of Indian frankincense in clinical practice and pharmaceutical development has substantially lagged behind. Recently the application of new formulation technologies resulted in a formulation of frankincense extract with lecithin, which revealed improved absorption and tissue penetration of BAs in a rodent study, leading for the first time to plasma concentrations of BAs in the range of their anti-inflammatory activity. In order to verify these encouraging results in humans, the absorption of a standardized Boswellia serrata extract (BE) and its lecithin formulation (CSP) was comparatively investigated in healthy volunteers. According to a randomized cross-over design with two treatments, two sequences and two periods, 12 volunteers alternatively received the lecithin-formulated Boswellia extract (CSP) or the non-formulated Boswellia extract (BE) at a dosage of 2×250mg capsules. The plasma concentrations of the six major BAs (KBA, AKBA, βBA, αBA, AβBA, AαBA) were determined using LC/MS. With the exception of KBA, a significantly higher (both in terms of weight-to-weight and molar comparison) and quicker absorption of BAs from the lecithin formulation was observed, leading to C max in the range required for the interaction with their molecular targets. These findings pave the way to further studies evaluating the clinical potential of BAs, and verify the beneficial effect of lecithin formulation to improve the absorption of poorly soluble phytochemicals. Copyright © 2016 The Authors. Published by Elsevier GmbH.. All rights reserved.

  18. Once-daily dosing of saquinavir and low-dose ritonavir in HIV-1-infected individuals: a pharmacokinetic pilot study

    NARCIS (Netherlands)

    van Heeswijk, R. P.; Veldkamp, A. I.; Mulder, J. W.; Meenhorst, P. L.; Lange, J. M.; Beijnen, J. H.; Hoetelmans, R. M.

    2000-01-01

    To investigate the steady-state pharmacokinetics of a once-daily dosing regimen of saquinavir soft gelatin capsules in combination with a low dose of ritonavir in HIV-1-infected individuals. Open-label, multi-dose, pharmacokinetic pilot study. Seven HIV-1-infected individuals who were treated with

  19. An open-label, sequential, dose-finding study of peginesatide for the maintenance treatment of anemia in chronic hemodialysis patients

    Directory of Open Access Journals (Sweden)

    Besarab Anatole

    2012-08-01

    Full Text Available Abstract Background Peginesatide is a peptide-based erythropoiesis-stimulating agent that was designed and engineered to stimulate specifically the erythropoietin receptor dimer that governs erythropoiesis. The primary objective of this phase 2 dose-finding study was to determine the once-monthly peginesatide dosing strategy that would maintain hemoglobin within ±1.0 g/dL of baseline values after conversion from epoetin alfa; the safety of peginesatide was evaluated concurrently. Methods Chronic hemodialysis patients on stable regimens of epoetin alfa were sequentially assigned to cohorts that differed on (1 how the peginesatide starting dose was determined (using a single epoetin alfa–to-peginesatide dose conversion ratio or a tiered, weight-based or absolute-dose conversion table and on (2 whether or not a 1-week erythropoiesis-stimulating agent-free interval was used. Peginesatide doses were titrated to maintain hemoglobin levels within ±1.0 g/dL from baseline. Results A total of 164 patients were enrolled and received intravenous peginesatide every 4 weeks for up to 6 doses; the duration of the study including follow-up was ≤29 weeks. Overall, the proportion of patients with hemoglobin levels within ±1.0 g/dL of baseline increased over the course of the study from 39% (Weeks 2–13 to 54% (Weeks 18–25. Cohorts that used tiered dose conversion tables trended towards having more stable peginesatide doses than did those cohorts that used a single dose conversion ratio. Moreover, cohorts that used an erythropoiesis-stimulating agent-free interval did not have the substantial initial increase in hemoglobin levels that was seen in those cohorts that did not use such an interval. In this study, the safety profile of peginesatide was consistent with those of marketed erythropoiesis-stimulating agents. Conclusions The results of this study were used to guide the dosing regimens used subsequently in phase 3 studies. Once

  20. An open randomized active-controlled clinical trial with low-dose SKA cytokines versus DMARDs evaluating low disease activity maintenance in patients with rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Martin-Martin LS

    2017-03-01

    Full Text Available LS Martin-Martin,1 F Giovannangeli,2 E Bizzi,2 U Massafra,2 E Ballanti,2 M Cassol,3 A Migliore2 1Department of Internal Medicine, Regina Apostolorum Hospital, 2Operative Unit of Rheumatology, 3Department of Internal Medicine, San Pietro Fatebenefratelli Hospital, Rome, Italy Background: Biologic agents are currently the strongest immunosuppressive drugs able to induce remission in rheumatoid arthritis (RA. One of the objectives of the medical scientific community now is how to maintain remission or low disease activity (LDA. The aim of this trial is to evaluate the contribution of low-dose sequential kinetic activation (SKA IL-4, IL-10, and anti-IL-1 antibodies (10 fg/mL in patients affected by RA in maintaining LDA or remission obtained after biological therapy. Method: This is a randomized, open, active-controlled, prospective, Phase IV trial. Disease activity score (DAS28, clinical disease activity index, simplified disease activity index, erythrocyte sedimentation rate and C-reactive protein levels, global health assessment, and pain visual analog scale were evaluated at baseline visit and then every 3 months together with an assessment of side effects till 12 months. Thirty-nine RA patients were enrolled and randomized to continue disease-modifying antirheumatic drugs (DMARDs therapy or to receive a combination of SKA low-dose cytokines formulated in concentration of 10 fg/mL orally administered at a dose of 20 drops/d for 12 consecutive months. Results: The rate of maintenance of LDA at 12 months was superior in the group treated with low-dose cytokines compared with patients treated with DMARDs, 66.7% and 42.1%, respectively; however, the difference between the groups was not statistically significant. No side effects were reported in both groups. Conclusion: This is the first study using a combination of three low-dose cytokines in RA, after data published on psoriasis. These data suggest that the use of a combination of low-dose SKA

  1. Effect of noninvasive vagus nerve stimulation on acute migraine: an open-label pilot study.

    Science.gov (United States)

    Goadsby, P J; Grosberg, B M; Mauskop, A; Cady, R; Simmons, K A

    2014-10-01

    We sought to assess a novel, noninvasive, portable vagal nerve stimulator (nVNS) for acute treatment of migraine. Participants with migraine with or without aura were eligible for an open-label, single-arm, multiple-attack study. Up to four migraine attacks were treated with two 90-second doses, at 15-minute intervals delivered to the right cervical branch of the vagus nerve within a six-week time period. Subjects were asked to self-treat at moderate or severe pain, or after 20 minutes of mild pain. Of 30 enrolled patients (25 females, five males, median age 39), two treated no attacks, and one treated aura only, leaving a Full Analysis Set of 27 treating 80 attacks with pain. An adverse event was reported in 13 patients, notably: neck twitching (n = 1), raspy voice (n = 1) and redness at the device site (n = 1). No unanticipated, serious or severe adverse events were reported. The pain-free rate at two hours was four of 19 (21%) for the first treated attack with a moderate or severe headache at baseline. For all moderate or severe attacks at baseline, the pain-free rate was 12/54 (22%). nVNS may be an effective and well-tolerated acute treatment for migraine in certain patients. © International Headache Society 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  2. Dose Titration of Pregabalin in Patients with Painful Diabetic Peripheral Neuropathy: Simulation Based on Observational Study Patients Enriched with Data from Randomized Studies.

    Science.gov (United States)

    Alexander, Joe; Edwards, Roger A; Manca, Luigi; Grugni, Roberto; Bonfanti, Gianluca; Emir, Birol; Whalen, Edward; Watt, Stephen; Parsons, Bruce

    2018-03-01

    Achieving a therapeutic response to pregabalin in patients with painful diabetic peripheral neuropathy (pDPN) requires adequate upward dose titration. Our goal was to identify relationships between titration and response to pregabalin in patients with pDPN. Data were integrated from nine randomized, placebo-controlled clinical trials as well as one 6-week open-label observational study conducted by 5808 physicians (2642 patients with pDPN) in standard outpatient settings in Germany. These studies evaluated pregabalin for treatment of pDPN. Using these data, we examined "what if" scenarios using a microsimulation platform that integrates data from randomized and observational sources as well as autoregressive-moving-average with exogenous inputs models that predict pain outcomes, taking into account weekly changes in pain, sleep interference, dose, and other patient characteristics that were unchanging. Final pain levels were significantly different depending on dose changes (P titration regardless of baseline pain severity. Altogether, 78.5% of patients with pDPN had 0-1 dose change, and 15.2% had ≥ 2 dose changes. Simulation demonstrated that the 4.8% of inadequately titrated patients who did not improve/very much improve their pain levels would have benefited from ≥ 2 dose changes. Patient satisfaction with tolerability (range 90.3-96.2%) was similar, regardless of baseline pain severity, number of titrations, or extent of improvement, suggesting that tolerability did not influence treatment response patterns. Upward dose titration reduced pain in patients with pDPN who actually received it. Simulation also predicted pain reduction in an inadequately titrated nonresponder subgroup of patients had they actually received adequate titration. The decision not to uptitrate must have been driven by factors other than tolerability. Pfizer, Inc.

  3. An open-label, non-randomized study of the pharmacokinetics of the nutritional supplement nicotinamide riboside (NR) and its effects on blood NAD+ levels in healthy volunteers.

    Science.gov (United States)

    Airhart, Sophia E; Shireman, Laura M; Risler, Linda J; Anderson, Gail D; Nagana Gowda, G A; Raftery, Daniel; Tian, Rong; Shen, Danny D; O'Brien, Kevin D

    2017-01-01

    The co-primary objectives of this study were to determine the human pharmacokinetics (PK) of oral NR and the effect of NR on whole blood nicotinamide adenine dinucleotide (NAD+) levels. Though mitochondrial dysfunction plays a critical role in the development and progression of heart failure, no mitochondria-targeted therapies have been translated into clinical practice. Recent murine studies have reported associations between imbalances in the NADH/NAD+ ratio with mitochondrial dysfunction in multiple tissues, including myocardium. Moreover, an NAD+ precursor, nicotinamide mononucleotide, improved cardiac function, while another NAD+ precursor, nicotinamide riboside (NR), improved mitochondrial function in muscle, liver and brown adipose. Thus, PK studies of NR in humans is critical for future clinical trials. In this non-randomized, open-label PK study of 8 healthy volunteers, 250 mg NR was orally administered on Days 1 and 2, then uptitrated to peak dose of 1000 mg twice daily on Days 7 and 8. On the morning of Day 9, subjects completed a 24-hour PK study after receiving 1000 mg NR at t = 0. Whole-blood levels of NR, clinical blood chemistry, and NAD+ levels were analyzed. Oral NR was well tolerated with no adverse events. Significant increases comparing baseline to mean concentrations at steady state (Cave,ss) were observed for both NR (p = 0.03) and NAD+ (p = 0.001); the latter increased by 100%. Absolute changes from baseline to Day 9 in NR and NAD+ levels correlated highly (R2 = 0.72, p = 0.008). Because NR increases circulating NAD+ in humans, NR may have potential as a therapy in patients with mitochondrial dysfunction due to genetic and/or acquired diseases.

  4. An open-label, non-randomized study of the pharmacokinetics of the nutritional supplement nicotinamide riboside (NR and its effects on blood NAD+ levels in healthy volunteers.

    Directory of Open Access Journals (Sweden)

    Sophia E Airhart

    Full Text Available The co-primary objectives of this study were to determine the human pharmacokinetics (PK of oral NR and the effect of NR on whole blood nicotinamide adenine dinucleotide (NAD+ levels.Though mitochondrial dysfunction plays a critical role in the development and progression of heart failure, no mitochondria-targeted therapies have been translated into clinical practice. Recent murine studies have reported associations between imbalances in the NADH/NAD+ ratio with mitochondrial dysfunction in multiple tissues, including myocardium. Moreover, an NAD+ precursor, nicotinamide mononucleotide, improved cardiac function, while another NAD+ precursor, nicotinamide riboside (NR, improved mitochondrial function in muscle, liver and brown adipose. Thus, PK studies of NR in humans is critical for future clinical trials.In this non-randomized, open-label PK study of 8 healthy volunteers, 250 mg NR was orally administered on Days 1 and 2, then uptitrated to peak dose of 1000 mg twice daily on Days 7 and 8. On the morning of Day 9, subjects completed a 24-hour PK study after receiving 1000 mg NR at t = 0. Whole-blood levels of NR, clinical blood chemistry, and NAD+ levels were analyzed.Oral NR was well tolerated with no adverse events. Significant increases comparing baseline to mean concentrations at steady state (Cave,ss were observed for both NR (p = 0.03 and NAD+ (p = 0.001; the latter increased by 100%. Absolute changes from baseline to Day 9 in NR and NAD+ levels correlated highly (R2 = 0.72, p = 0.008.Because NR increases circulating NAD+ in humans, NR may have potential as a therapy in patients with mitochondrial dysfunction due to genetic and/or acquired diseases.

  5. Monte Carlo simulation of second-generation open-type PET ''single-ring OpenPET'' implemented with DOI detectors

    International Nuclear Information System (INIS)

    Tashima, Hideaki; Yamaya, Taiga; Hirano, Yoshiyuki; Yoshida, Eiji; Kinouch, Shoko; Watanabe, Mitsuo; Tanaka, Eiichi

    2013-01-01

    At the National Institute of Radiological Sciences, we are developing OpenPET, an open-type positron emission tomography (PET) geometry with a physically open space, which allows easy access to the patient during PET studies. Our first-generation OpenPET system, dual-ring OpenPET, which consisted of two detector rings, could provide an extended axial field of view (FOV) including the open space. However, for applications such as in-beam PET to monitor the dose distribution in situ during particle therapy, higher sensitivity concentrated on the irradiation field is required rather than a wide FOV. In this report, we propose a second-generation OpenPET geometry, single-ring OpenPET, which can efficiently improve sensitivity while providing the required open space. When the proposed geometry was realized with block detectors, position-dependent degradation of the spatial resolution was expected because it was necessary to arrange the detector blocks in ellipsoidal rings stacked and shifted relative to one another. However, we found by Monte Carlo simulation that the use of depth-of-interaction (DOI) detectors made it feasible to achieve uniform spatial resolution in the FOV. (author)

  6. Validation of single-sample doubly labeled water method

    International Nuclear Information System (INIS)

    Webster, M.D.; Weathers, W.W.

    1989-01-01

    We have experimentally validated a single-sample variant of the doubly labeled water method for measuring metabolic rate and water turnover in a very small passerine bird, the verdin (Auriparus flaviceps). We measured CO 2 production using the Haldane gravimetric technique and compared these values with estimates derived from isotopic data. Doubly labeled water results based on the one-sample calculations differed from Haldane values by less than 0.5% on average (range -8.3 to 11.2%, n = 9). Water flux computed by the single-sample method differed by -1.5% on average from results for the same birds based on the standard, two-sample technique (range -13.7 to 2.0%, n = 9)

  7. Pharmacokinetics and bioavailability of oxycodone and acetaminophen following single-dose administration of MNK-795, a dual-layer biphasic IR/ER combination formulation, under fed and fasted conditions

    Directory of Open Access Journals (Sweden)

    Devarakonda K

    2014-08-01

    Full Text Available Krishna Devarakonda,1 Terri Morton,1 Rachel Margulis,2 Michael Giuliani,3 Thomas Barrett4 1Clinical Pharmacology and Pharmacokinetics, 2Clinical Operations, 3Research and Development, 4Clinical Affairs, Mallinckrodt Inc., Hazelwood, MO, USA Background: XARTEMIS™ XR (formerly MNK-795 is a combination oxycodone (OC and acetaminophen (APAP analgesic with both immediate-release and extended-release (ER components (ER OC/APAP. The tablets are designed with gastric-retentive ER oral delivery technology that releases the ER component at a controlled rate in the upper gastrointestinal tract. Because consumption of food has demonstrated an impact on the pharmacokinetics (PK of some marketed products using gastric-retentive ER oral delivery technology, a characterization of the effects of fed (high- and low-fat diets versus fasted conditions on the PK of ER OC/APAP was performed. Methods: This Phase I study used an open-label randomized single-dose three-period six-sequence crossover single-center design. Healthy adult participants (n=48 were randomized to receive two tablets of ER OC/APAP under three conditions: following a high-fat meal; following a low-fat meal; and fasted. Plasma concentration versus time data from predose throughout designated times up to 48 hours postdose was used to estimate the PK parameters of oxycodone and APAP. Results: Thirty-one participants completed all three treatment periods. Both oxycodone and APAP were rapidly absorbed under fasted conditions. Total oxycodone and APAP exposures (area under the plasma drug concentration-time curve [AUC] from ER OC/APAP were not significantly affected by food, and minimal changes to maximum observed plasma concentration for oxycodone and APAP were also noted. However, food marginally delayed the time to maximum observed plasma concentration of oxycodone and APAP. There was no indication that tolerability was affected by food. Conclusion: The findings from this study suggest that ER OC

  8. Randomized clinical trial to comparing efficacy of daily, weekly and monthly administration of vitamin D3.

    Science.gov (United States)

    Takács, István; Tóth, Béla E; Szekeres, László; Szabó, Boglárka; Bakos, Bence; Lakatos, Péter

    2017-01-01

    The comparative efficacy and safety profiles of selected daily 1000 IU, weekly 7000 IU and monthly 30,000 IU vitamin D 3 -not previously investigated-will be evaluated. Here, a prospective, randomized clinical trial, comparing efficacy and safety of a daily single dose of 1000 IU (group A) to a once-weekly 7000 IU dose (group B), or monthly 30,000 IU dose (group C) of vitamin D 3 . The present study is a controlled, randomized, open-label, multicenter clinical trial, 3  months in duration. Sixty-four adult subjects with vitamin D deficiency (25OHD<20 ng/ml), were included according to the inclusion and exclusion criteria. Dose-responses for increases in serum vitamin 25OHD were statistically equivalent for each of the three groups: A, B and C. Outcomes were 13.0 ± 1.5; 12.6 ± 1.1 and 12.9 ± 0.9 ng/ml increases in serum 25OHD per 1000 IU, daily, weekly and monthly, respectively. The treatment of subjects with selected doses restored 25OHD values to levels above 20 ng/ml in all groups. Treatment with distinct administration frequency of vitamin D 3 did not exhibit any differences in safety parameters. The daily, weekly and monthly administrations of daily equivalent of 1000 IU of vitamin D 3 provide equal efficacy and safety profiles.

  9. Self-reference and random sampling approach for label-free identification of DNA composition using plasmonic nanomaterials.

    Science.gov (United States)

    Freeman, Lindsay M; Pang, Lin; Fainman, Yeshaiahu

    2018-05-09

    The analysis of DNA has led to revolutionary advancements in the fields of medical diagnostics, genomics, prenatal screening, and forensic science, with the global DNA testing market expected to reach revenues of USD 10.04 billion per year by 2020. However, the current methods for DNA analysis remain dependent on the necessity for fluorophores or conjugated proteins, leading to high costs associated with consumable materials and manual labor. Here, we demonstrate a potential label-free DNA composition detection method using surface-enhanced Raman spectroscopy (SERS) in which we identify the composition of cytosine and adenine within single strands of DNA. This approach depends on the fact that there is one phosphate backbone per nucleotide, which we use as a reference to compensate for systematic measurement variations. We utilize plasmonic nanomaterials with random Raman sampling to perform label-free detection of the nucleotide composition within DNA strands, generating a calibration curve from standard samples of DNA and demonstrating the capability of resolving the nucleotide composition. The work represents an innovative way for detection of the DNA composition within DNA strands without the necessity of attached labels, offering a highly sensitive and reproducible method that factors in random sampling to minimize error.

  10. Immunogenicity of simultaneous versus sequential administration of a 23-valent pneumococcal polysaccharide vaccine and a quadrivalent influenza vaccine in older individuals: A randomized, open-label, non-inferiority trial.

    Science.gov (United States)

    Nakashima, Kei; Aoshima, Masahiro; Ohfuji, Satoko; Yamawaki, Satoshi; Nemoto, Masahiro; Hasegawa, Shinya; Noma, Satoshi; Misawa, Masafumi; Hosokawa, Naoto; Yaegashi, Makito; Otsuka, Yoshihito

    2018-03-21

    It is unclear whether simultaneous administration of a 23-valent pneumococcal polysaccharide vaccine (PPSV23) and a quadrivalent influenza vaccine (QIV) produces immunogenicity in older individuals. This study tested the hypothesis that the pneumococcal antibody response elicited by simultaneous administration of PPSV23 and QIV in older individuals is not inferior to that elicited by sequential administration of PPSV23 and QIV. We performed a single-center, randomized, open-label, non-inferiority trial comprising 162 adults aged ≥65 years randomly assigned to either the simultaneous (simultaneous injections of PPSV23 and QIV) or sequential (control; PPSV23 injected 2 weeks after QIV vaccination) groups. Pneumococcal immunoglobulin G (IgG) titers of serotypes 23F, 3, 4, 6B, 14, and 19A were assessed. The primary endpoint was the serotype 23F response rate (a ≥2-fold increase in IgG concentrations 4-6 weeks after PPSV23 vaccination). With the non-inferiority margin set at 20% fewer patients, the response rate of serotype 23F in the simultaneous group (77.8%) was not inferior to that of the sequential group (77.6%; difference, 0.1%; 90% confidence interval, -10.8% to 11.1%). None of the pneumococcal IgG serotype titers were significantly different between the groups 4-6 weeks after vaccination. Simultaneous administration did not show a significant decrease in seroprotection odds ratios for H1N1, H3N2, or B/Phuket influenza strains other than B/Texas. Additionally, simultaneous administration did not increase adverse reactions. Hence, simultaneous administration of PPSV23 and QIV shows an acceptable immunogenicity that is comparable to sequential administration without an increase in adverse reactions. (This study was registered with ClinicalTrials.gov [NCT02592486]).

  11. Integrated MRSA-Management (IMM with prolonged decolonization treatment after hospital discharge is effective: a single centre, non-randomised open-label trial

    Directory of Open Access Journals (Sweden)

    Bernhard Jahn

    2016-06-01

    Full Text Available Abstract Background Guidelines for the control of hospital-acquired MRSA include decolonization measures to end MRSA carrier status in colonized and infected patients. Successful decolonization typically requires up to 22 days of treatment, which is longer than the average hospital length of stay (LOS. Incomplete decolonization is therefore common, with long-term MRSA carriage as a consequence. To overcome this, we developed an integrated MRSA Management (IMM by extending MRSA decolonization to the outpatient and domestic setting. The protocol makes use of polyhexanide-based products, in view of reported qac-mediated resistance to chlorhexidine in S. aureus and MRSA. Methods This is a prospective, single centre, controlled, non-randomized, open-label study to evaluate the efficiency of the IMM concept. The outcome of guideline-approved decolonization during hospital stay only (control group; n = 201 was compared to the outcome following IMM treatment whereby decolonization was continued after discharge in the domestic setting or in a long-term care facility (study group; n = 99. As a secondary outcome, the effect of MRSA-status of skin alterations was assessed. Results The overall decolonization rate was 47 % in the IMM patient group compared to 12 % in the control group (p  0.05. For patients with skin alterations (e.g. wounds and entry sites, decolonization success was 50 % if the skin alterations were MRSA-negative at baseline, compared to 22 % success for patients entering the study with MRSA-positive skin alterations (p < 0.01. Conclusions The IMM strategy offers an MRSA decolonization protocol that is feasible in the domestic setting and is equally effective compared with inpatient decolonization treatment when hospital LOS is long enough to complete the treatment. Moreover, for patients with average LOS, decolonization rates obtained with IMM are significantly higher than for in-hospital treatment. IMM is a promising

  12. An evaluation of total disintegration time for three different doses of sublingual fentanyl tablets in patients with breakthrough pain.

    Science.gov (United States)

    Nalamachu, Srinivas

    2013-12-01

    Breakthrough pain is common among patients with cancer and presents challenges to effective pain management. Breakthrough pain is characterized by rapid onset, severe intensity, and duration typically lasting disintegration time of three different doses of sublingual fentanyl tablets in opioid-tolerant patients. This was a single-center, non-randomized, open-label study. Opioid-tolerant adult patients (N = 30) with chronic pain were assigned to one of three dose groups and self-administered a single 100, 200, or 300 μg sublingual fentanyl tablet (Abstral(®), Galena Biopharma, Portland, OR, USA). Time to complete disintegration was measured by each patient with a stopwatch and independently verified by study personnel. Disintegration time (mean ± SD) for sublingual fentanyl tablets (all doses) was 88.2 ± 55.1 s. Mean disintegration times tended to be slightly longer for the 200 μg (96.7 ± 57.9 s) and 300 μg doses (98.6 ± 64.8 s) compared to the 100 μg dose (69.5 ± 40.5 s). Differences were not statistically significant. Disintegration time was not significantly different between men and women and was not affected by age. Sublingual fentanyl tablets dissolved rapidly (average time <2 min) in all patients, with the higher doses taking slightly more time to dissolve.

  13. Differential Effects of Acetylcholinesterase Inhibitors on Clinical Responses and Cerebral Blood Flow Changes in Patients with Alzheimer's Disease: A 12-Month, Randomized, and Open-Label Trial

    Directory of Open Access Journals (Sweden)

    Soichiro Shimizu

    2015-04-01

    Full Text Available Background/Aims: The present study evaluated the differences in treatment outcomes and brain perfusion changes among 3 types of acetylcholinesterase inhibitors (AchEIs, i.e. donepezil, rivastigmine, and galantamine. Methods: This was a prospective, longitudinal, randomized, open-label, 3-arm (donepezil, rivastigmine, or galantamine, parallel-group, 12-month clinical trial carried out in 55 patients with AD. Results: At 6 months, the results of the Mini-Mental State Examination (MMSE and the Trail Making Test (TMT-Part A showed an improvement versus baseline in the donepezil treatment group. All groups showed a significant increase in regional cerebral blood flow (rCBF, mainly in the frontal lobe. Significant rCBF reduction was observed in the temporal lobe and cingulate gyrus in all 3 groups. Conclusion: AchEI treatment prevents the progression of cognitive impairment and increases the relative rCBF in the frontal lobe.

  14. Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression: A SPECT Study.

    Science.gov (United States)

    Sanches, Rafael Faria; de Lima Osório, Flávia; Dos Santos, Rafael G; Macedo, Ligia R H; Maia-de-Oliveira, João Paulo; Wichert-Ana, Lauro; de Araujo, Draulio Barros; Riba, Jordi; Crippa, José Alexandre S; Hallak, Jaime E C

    2016-02-01

    Ayahuasca is an Amazonian botanical hallucinogenic brew which contains dimethyltryptamine, a 5-HT2A receptor agonist, and harmine, a monoamine-oxidase A inhibitor. Our group recently reported that ayahuasca administration was associated with fast-acting antidepressive effects in 6 depressive patients. The objective of the present work was to assess the antidepressive potentials of ayahuasca in a bigger sample and to investigate its effects on regional cerebral blood flow. In an open-label trial conducted in an inpatient psychiatric unit, 17 patients with recurrent depression received an oral dose of ayahuasca (2.2 mL/kg) and were evaluated with the Hamilton Rating Scale for Depression, the Montgomery-Åsberg Depression Rating Scale, the Brief Psychiatric Rating Scale, the Young Mania Rating Scale, and the Clinician Administered Dissociative States Scale during acute ayahuasca effects and 1, 7, 14, and 21 days after drug intake. Blood perfusion was assessed eight hours after drug administration by means of single photon emission tomography. Ayahuasca administration was associated with increased psychoactivity (Clinician Administered Dissociative States Scale) and significant score decreases in depression-related scales (Hamilton Rating Scale for Depression, Montgomery-Åsberg Depression Rating Scale, Brief Psychiatric Rating Scale) from 80 minutes to day 21. Increased blood perfusion in the left nucleus accumbens, right insula and left subgenual area, brain regions implicated in the regulation of mood and emotions, were observed after ayahuasca intake. Ayahuasca was well tolerated. Vomiting was the only adverse effect recorded, being reported by 47% of the volunteers. Our results suggest that ayahuasca may have fast-acting and sustained antidepressive properties. These results should be replicated in randomized, double-blind, placebo-controlled trials.

  15. A dose-response study of dexmedetomidine administered as the primary sedative in infants following open heart surgery.

    Science.gov (United States)

    Su, Felice; Nicolson, Susan C; Zuppa, Athena F

    2013-06-01

    To evaluate the dose-response relationship of dexmedetomidine in infants with congenital heart disease postoperative from open heart surgery. Prospective open-label dose-escalation pharmacokinetic-pharmacodynamic study. Tertiary pediatric cardiac ICU. Thirty-six evaluable infants, 1-24 months old, postoperative from open heart surgery requiring mechanical ventilation. Cohorts of 12 infants were enrolled sequentially to one of the three IV loading doses of dexmedetomidine (0.35, 0.7, and 1 mcg/kg) over 10 minutes followed by respective continuous infusions (0.25, 0.5, and 0.75 mcg/kg/hr) for up to 24 hours. Dexmedetomidine plasma concentrations were obtained at timed intervals during and following discontinuation of infusion. Pharmacodynamic variables evaluated included sedation scores, supplemental sedation and analgesia medication administration, time to tracheal extubation, respiratory function, and hemodynamic parameters. Infants achieved a deeper sedation measured by the University of Michigan Sedation Scale score (2.6 vs 1) despite requiring minimal supplemental sedation (0 unit doses/hr) and fewer analgesic medications (0.07 vs 0.15 unit doses/hr) while receiving dexmedetomidine compared with the 12-hour follow-up period. Thirty-one patients were successfully extubated while receiving the dexmedetomidine infusion. Only one patient remained intubated due to oversedation during the infusion. While receiving dexmedetomidine, there was a decrease in heart rate compared with baseline, 132 versus 161 bpm, but there was an increase in heart rate compared with postinfusion values, 132 versus 128 bpm. There was no statistically or clinically significant change in mean arterial blood pressure. Dexmedetomidine administration in infants following open heart surgery can provide improved sedation with reduction in supplemental medication requirements, leading to successful extubation while receiving a continuous infusion. The postoperative hemodynamic changes that occur in

  16. Intramuscular olanzapine versus intramuscular haloperidol plus lorazepam for the treatment of acute schizophrenia with agitation: An open-label, randomized controlled trial.

    Science.gov (United States)

    Huang, Charles Lung-Cheng; Hwang, Tzung-Jeng; Chen, Yi-Hsing; Huang, Guan-Hua; Hsieh, Ming H; Chen, Hsiu-Hsi; Hwu, Hai-Gwo

    2015-05-01

    To compare the efficacy and safety profile between intramuscular (IM) olanzapine and IM haloperidol plus IM lorazepam in acute schizophrenic patients with moderate to severe agitation. This was a prospective, randomized, open-label study. Acutely agitated patients with schizophrenia or schizoaffective disorder (n = 67) were randomized to receive 10 mg IM olanzapine (n = 37) or 5 mg IM haloperidol plus 2 mg IM lorazepam (n = 30). Agitation was measured with Positive and Negative Syndrome Scale Excited Component (PANSS-EC) and Agitation-Calmness Evaluation Scale (ACES) during the first 2 hours and at 24 hours after the first injection. Safety was assessed using the Simpson-Angus Scale and Barnes Akathisia Rating Scale and by recording adverse events at 24 hours following the first injection. The Clinical Global Impression-Severity scale was also rated. The PANSS-EC scores decreased significantly at 2 hours after the first injection in both groups (olanzapine: -10.2, p haloperidol + lorazepam: -9.9, p Haloperidol plus lorazepam was not inferior to olanzapine in reducing agitation at 2 hours. There were no significant differences in PANSS-EC or ACES scores between the two groups within 2 hours following the first injection. The frequencies of adverse events and changes in Clinical Global Impression-Severity, Simpson-Angus Scale, and Barnes Akathisia Rating Scale scores from baseline to 24 hours showed no significant differences between the groups. The findings suggest that IM haloperidol (5 mg) plus lorazepam (2 mg) is not inferior to IM olanzapine (10 mg) in the treatment of acute schizophrenic patients with moderate to severe agitation (ClinialTrials.gov identifier number NCT00797277). Copyright © 2015. Published by Elsevier B.V.

  17. Effect of Vitamin D supplementation on glycemic parameters and progression of prediabetes to diabetes: A 1-year, open-label randomized study

    Directory of Open Access Journals (Sweden)

    Mohammad Shafi Kuchay

    2015-01-01

    Full Text Available Background: Whether Vitamin D supplementation in prediabetes subjects prevents the development of diabetes is a matter of debate, and the results are inconsistent. This open-label, randomized study in subjects with prediabetes evaluated the effect of 12 months of Vitamin D supplementation on glycemic parameters and progression of prediabetes to diabetes in an ethnically homogeneous Kashmiri population. Materials and Methods: A total of 147 subjects were diagnosed as prediabetes out of which 137 subjects were randomized to receive in addition to standard lifestyle measures, either Vitamin D 60,000 IU weekly for 4 weeks and then 60,000 IU monthly (n = 69 or no Vitamin D (n = 68. Fasting plasma glucose (FPG, 2-h plasma glucose and A1C levels were estimated at 0, 6 and 12 months. Changes in FPG, 2-h plasma glucose, A1C level and the proportion of subjects developing diabetes were assessed among 129 subjects. Results: At 12 months, A1C levels were significantly lesser (5.7% ± 0.4% in the Vitamin D supplemented group when compared with non-Vitamin D supplemented (6.0% ± 0.3%. Similarly, FPG (97 ± 7 and 2-h plasma glucose (132 ± 16 were significantly less in Vitamin D supplemented group as compared with non-Vitamin D supplemented group (FPG = 116 ± 6 and 2-h plasma glucose = 157 ± 25 at 12 months. Nine out of 65 in non-Vitamin D supplemented and seven out of 64 in the Vitamin D supplemented group developed diabetes. Conclusions: Vitamin D supplementation in prediabetes subjects significantly lowered FPG, 2-h plasma glucose and A1C levels.

  18. Aripiprazole for Irritability in Asian Children and Adolescents with Autistic Disorder: A 12-Week, Multinational, Multicenter, Prospective Open-Label Study.

    Science.gov (United States)

    Kim, Hyo-Won; Park, Eun-Jin; Kim, Ji-Hoon; Boon-Yasidhi, Vitharon; Tarugsa, Jariya; Reyes, Alexis; Manalo, Stella; Joung, Yoo-Sook

    2018-04-24

    We investigated the effectiveness and tolerability of aripiprazole in the treatment of irritability in Asian children and adolescents (6-17 years) with autistic disorder in a 12-week, multinational, multicenter, open-label study. Sixty-seven subjects (10.0 ± 3.1 years old, 52 boys) were enrolled and treated with flexibly dosed aripiprazole for 12 weeks (mean dose, 5.1 ± 2.5 mg; range 2-15 mg). Aripiprazole significantly reduced the mean caregiver-rated scores for the Irritability, Lethargy/Social Withdrawal, Stereotypy, Hyperactivity, and Inappropriate Speech subscales of the Aberrant Behavior Checklist from baseline to week 12 (p autistic disorder. Further studies with larger sample sizes and longer treatment durations are required.

  19. EffenDys-Fentanyl Buccal Tablet for the Relief of Episodic Breathlessness in Patients With Advanced Cancer: A Multicenter, Open-Label, Randomized, Morphine-Controlled, Crossover, Phase II Trial.

    Science.gov (United States)

    Simon, Steffen T; Kloke, Marianne; Alt-Epping, Bernd; Gärtner, Jan; Hellmich, Martin; Hein, Rebecca; Piel, Maren; Cornely, Oliver A; Nauck, Friedemann; Voltz, Raymond

    2016-11-01

    Episodic breathlessness is a frequent and burdensome symptom in cancer patients but pharmacological treatment is limited. To determine time to onset, efficacy, feasibility, and safety of transmucosal fentanyl in comparison to immediate-release morphine for the relief of episodic breathlessness. Phase II, investigator-initiated, multicenter, open-label, randomized, morphine-controlled, crossover trial with open-label titration of fentanyl buccal tablet (FBT) in inpatients with incurable cancer. The primary outcome was time to onset of meaningful breathlessness relief. Secondary outcomes were efficacy (breathlessness intensity difference at 10 and 30 minutes; sum of breathlessness intensity difference at 15 and 60 minutes), feasibility, and safety. Study was approved by local ethics committees. Twenty-five of 1341 patients were eligible, 10 patients agreed to participate (four female, mean age 58 ± 11, mean Karnofsky score 67 ± 11). Two patients died before final visits and two patients dropped-out because of disease progression leaving six patients for analysis with 61 episodes of breathlessness. Mean time to onset was for FBT 12.7 ± 10.0 and for immediate-release morphine 23.6 ± 15.1 minutes with a mean difference of -10.9 minutes (95% CI = -24.5 to 2.7, P = 0.094). Efficacy measures were predominately in favor for FBT. Both interventions were safe. Feasibility failed because of too much study demands for a very ill patient group. The description of a faster and greater relief of episodic breathlessness by transmucosal fentanyl versus morphine justifies further evaluation by a full-powered trial. Copyright © 2016. Published by Elsevier Inc.

  20. A Systematic Review on Effect of Single-Dose Preoperative Antibiotics at Surgical Osteotomy Extraction of Lower Third Molars

    DEFF Research Database (Denmark)

    Marcussen, Karoline Brørup; Laulund, Anne Sofie; Jørgensen, Henrik L

    2016-01-01

    PURPOSE: We conducted a systematic review of randomized controlled trials (RCTs) to evaluate the effectiveness of a single dose of preoperative antibiotic administered perorally, intravenously, intramuscularly, or topically for preventing infection and alveolar osteitis in lower third molar...... that penicillin V was effective in reducing the incidence of alveolar osteitis (OR = 0.1; 95% CI, 0.03 to 0.30; P ≤ .0001). CONCLUSIONS: A single oral dose of 2 g of amoxicillin before lower third molar osteotomy surgical extraction significantly decreased the incidence of SSI. A single dose of 0.8 g...... of penicillin V before lower third molar osteotomy surgical extraction significantly decreased the incidence of alveolar osteitis....

  1. Safe and Effective Use of the Once Weekly Dulaglutide Single-Dose Pen in Injection-Naïve Patients With Type 2 Diabetes.

    Science.gov (United States)

    Matfin, Glenn; Van Brunt, Kate; Zimmermann, Alan G; Threlkeld, Rebecca; Ignaut, Debra A

    2015-04-21

    This 4-week, phase 3b, multicenter, open-label, single-arm, outpatient study demonstrated the safe and effective use of the dulaglutide single-dose pen containing 0.5 mL of placebo for subcutaneous injection in injection-naïve adult patients with type 2 diabetes (T2D), with A1C ≤ 8.5% (69 mmol/mol), BMI ≥ 23 kg/m2 and ≤ 45 kg/m(2). Patients completed a modified self-injecting subscale of the Diabetes Fear of Injecting and Self-Testing Questionnaire (mD-FISQ) and were trained to self-inject with the single-dose pen. Patients completed the initial self-injection at the site, injected at home for 2 subsequent weeks, and returned to the site for the final injection. The initial and final self-injections were evaluated for success; the final (initial) self-injection success rate was the primary (secondary) outcome measure, and the primary (secondary) objective was to demonstrate this success rate as being significantly greater than 80%. Patients recorded their level of pain after each injection. After the final injection, patients completed the mD-FISQ and the Medication Delivery Device Assessment Battery (MDDAB) to assess their perceptions of the single-dose pen, including ease of use and experience with the device. Among 211 patients (mean age: 61 years), the primary objective was met, with a final injection success rate of 99.1% (95% CI: 96.6% to 99.7%). Among 214 patients, the initial injection success rate was 97.2% (95% CI: 94.0% to 98.7%), meeting the key secondary objective. Overall, most patients (>96%) found the device easy to use, were satisfied with the device, and would be willing to continue to use the single-dose pen after the study. There was a significant reduction (P injecting, as measured by the mD-FISQ. The dulaglutide single-dose pen was found to be a safe and effective device for use by patients with T2D who were injection-naïve. A positive injection experience is an important factor for patients and providers when initiating injectable

  2. Lorlatinib in non-small-cell lung cancer with ALK or ROS1 rearrangement: an international, multicentre, open-label, single-arm first-in-man phase 1 trial.

    Science.gov (United States)

    Shaw, Alice T; Felip, Enriqueta; Bauer, Todd M; Besse, Benjamin; Navarro, Alejandro; Postel-Vinay, Sophie; Gainor, Justin F; Johnson, Melissa; Dietrich, Jorg; James, Leonard P; Clancy, Jill S; Chen, Joseph; Martini, Jean-François; Abbattista, Antonello; Solomon, Benjamin J

    2017-12-01

    Most patients with anaplastic lymphoma kinase (ALK)-rearranged or ROS proto-oncogene 1 (ROS1)-rearranged non-small-cell lung cancer (NSCLC) are sensitive to tyrosine kinase inhibitor (TKI) therapy, but resistance invariably develops, commonly within the CNS. This study aimed to analyse the safety, efficacy, and pharmacokinetic properties of lorlatinib, a novel, highly potent, selective, and brain-penetrant ALK and ROS1 TKI with preclinical activity against most known resistance mutations, in patients with advanced ALK-positive or ROS1-positive NSCLC. In this international multicentre, open-label, single-arm, first-in-man phase 1 dose-escalation study, eligible patients had advanced ALK-positive or ROS1-positive NSCLC and were older than 18 years, with an Eastern Cooperative Oncology Group performance status of 0 or 1, and adequate end-organ function. Lorlatinib was administered orally to patients at doses ranging from 10 mg to 200 mg once daily or 35 mg to 100 mg twice daily, with a minimum of three patients receiving each dose. For some patients, tumour biopsy was done before lorlatinib treatment to identify ALK resistance mutations. Safety was assessed in patients who received at least one dose of lorlatinib; efficacy was assessed in the intention-to-treat population (patients who received at least one dose of study treatment and had either ALK or ROS1 rearrangement). The primary endpoint was dose-limiting toxicities during cycle 1 according to investigator assessment; secondary endpoints included safety, pharmacokinetics, and overall response. This study is ongoing and is registered with ClinicalTrials.gov, number NCT01970865. Between Jan 22, 2014, and July 10, 2015, 54 patients received at least one dose of lorlatinib, including 41 (77%) with ALK-positive and 12 (23%) with ROS1-positive NSCLC; one patient had unconfirmed ALK and ROS1 status. 28 (52%) patients had received two or more TKIs, and 39 (72%) patients had CNS metastases. The most common treatment

  3. Onabotulinumtoxin A Treatment of Drooling in Children with Cerebral Palsy: A Prospective, Longitudinal Open-Label Study

    DEFF Research Database (Denmark)

    Møller, Eigild; Pedersen, Søren Anker; Vinicoff, Pablo Gustavo

    2015-01-01

    The aim of this prospective open-label study was to treat disabling drooling in children with cerebral palsy (CP) with onabotulinumtoxin A (A/Ona, Botox®) into submandibular and parotid glands and find the lowest effective dosage and least invasive method. A/Ona was injected in 14 children, Mean...... age 9 years, SD 3 years, under ultrasonic guidance in six successive Series, with at least six months between injections. Doses and gland involvement increased from Series A to F (units (U) per submandibular/parotid gland: A, 10/0; B, 15/0; C, 20/0; D, 20/20; E, 30/20; and F, 30/30). The effect...... in E and F, but with swallowing problems ≤5 weeks in 3 of 28 treatments. F had largest VAS and UWS reduction (64% and 49%). We recommend: Start with dose D A/Ona (both submandibular and parotid glands and a total of 80 U) and increase to E and eventually F (total 120 U) without sufficient response....

  4. Dose proportionality and pharmacokinetics of carvedilol sustained-release formulation: a single dose-ascending 10-sequence incomplete block study

    Directory of Open Access Journals (Sweden)

    Kim YH

    2015-06-01

    Full Text Available Yo Han Kim,1 Hee Youn Choi,1 Yook-Hwan Noh,1 Shi Hyang Lee,1 Hyeong-Seok Lim,1 Chin Kim,2 Kyun-Seop Bae11Department of Clinical Pharmacology and Therapeutics, College of Medicine, University of Ulsan, Asan Medical Center, 2Chong Kun Dang Clinical Research and Clinical Epidemiology and Medical Information, CKD Pharmaceuticals, Seoul, Republic of KoreaBackground: Carvedilol is a third-generation β-blocker indicated for congestive heart failure and high blood pressure. The aim of this study was to investigate the dose proportionality of the carvedilol sustained-release (SR formulation in healthy male subjects.Methods: An open-label, single dose-ascending, 10-sequence, 3-period balanced incomplete block study was performed using healthy male subjects. In varying sequences, each subject received three of five carvedilol SR formulations (8, 16, 32, 64, or 128 mg once. The treatment periods were separated by a washout period of 7 days. Serial blood samples were collected up to 48 h after dosing. The plasma concentrations of carvedilol were determined by using validated liquid chromatography–tandem mass spectrometry. Pharmacokinetic parameters including the area under the plasma concentration–time curve (AUC from time 0 to the last measurable time (AUClast, AUC extrapolated to infinity (AUCinf, and the measured peak plasma concentration (Cmax were obtained by noncompartmental analysis. Dose proportionality was evaluated if the ln–ln plots of AUClast, AUCinf, and Cmax versus dose were linear and the 90% confidence intervals (CIs of the slopes were within 0.9195 and 1.0805. Tolerability was assessed by vital signs, electrocardiogram, clinical laboratory tests, and monitoring of adverse events (AEs throughout the study.Results: A total of 31 subjects were enrolled, and 30 completed the study. The assessment of dose proportionality meets the statistical criteria; the point estimates of slope were 1.0104 (90% CI: 0.9849–1.0359 for AUClast, 1

  5. Distribution of 99Tcm-rh-Annexin V and its relationship with expression of survivin and Caspase-3 in tumors after a single dose of chemotherapy

    International Nuclear Information System (INIS)

    Zhang Xin; Zhang Yanjun; Tao Li; Zhu Yi; Yang Chun; Li Yaming; Zhang Jianying; Zhao Zhenzhen; Ji Xiaopeng; Zhao Ming; Tian Aijuan

    2008-01-01

    Objective: Recently, molecular imaging for detecting cellular apoptosis is developing rapidly. The aim of the study was to determine the effectiveness of imaging with 99 Tc m labelled recombinant human Annexin V ( 99 Tc m -rh-Annexin V) as a reflection of apoptosis in tumor, and related its distribution with expression of Survivin and Caspase-3 after a single dose of chemotherapy. Methods: Eight days after being inoculated with allogenic hepatoma cells (Hca-F25) into right axillary fossa, the mice (purebred 615) were randomly divided into two groups (control group A, n=9; and treated group B, n=10). Group B was received a single dose of chemotherapy intraperitoneally (cyclophosphamide, 150 mg/kg). Groups A and B were given 99 Tc m -rh-AnnexinV (3.7 MBq·0.5 μg -1 per mouse) intravenously 20 h later. Four hours after 99 Tc m -rh-Annexin V injection, the animals were imaged and sacrificed, and the tumor samples were weighed and the radioactivity was determined in a well-counter. The accumulation of 99 Tc m -rh-Annexin V in tumor was expressed as the percentage activity of injection dose per gram of tissue (% ID/g). Tumor cell apoptosis was examined by terminal deoxynueleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) method, and the expression of Survivin and Caspase-3 in tumor were determined with immunohistochemical method. SPSS 10.0 was used for data analysis. Results: Single dose chemotherapy tsignificantly increased the tumor uptake of 99 Tc m -rh-Annexin V [(0.478 ± 0.123)% ID/g vs (0.332 ± 0.061)% ID/g] and the positive number of TUNEL [(18.030 ± 5.600) cells/field vs (6.744 ± 2.325) cells/field], as well as the expression of Caspase-3 [(3.266 ± 0.482)% vs (2.387 ± 0.387)%, F was 10.502, 31.507, 18.971, respectively, all P 99 Tc m -rh-Annexin V correlated positively well with the expression of Caspase-3 and negatively with the expression of Survivin (P 99 Tc m -rh-Annexin V can not only reflect the extent of apoptosis

  6. Efficacy and safety of saxagliptin in combination with insulin in Japanese patients with type 2 diabetes mellitus: a 16-week double-blind randomized controlled trial with a 36-week open-label extension.

    Science.gov (United States)

    Kadowaki, Takashi; Muto, Satsuki; Ouchi, Yoshiumi; Shimazaki, Ryutaro; Seino, Yutaka

    2017-12-01

    We examined the efficacy and safety of saxagliptin as an add-on to insulin in Japanese patients with type 2 diabetes mellitus. We randomized 240 patients with type 2 diabetes mellitus on insulin monotherapy to 5-mg saxagliptin or placebo as add-on therapy for a 16-week, double-blind period. All patients received 5-mg saxagliptin and insulin for an additional 36 weeks (open-label extension). Change in hemoglobin A1c (HbA1c) at Week 16 was the main endpoint. At Week 16, the adjusted change in HbA1c from baseline increased by 0.51% with placebo and decreased by 0.40% with saxagliptin (difference -0.92% [95% confidence interval -1.07%, -0.76%; p 1]). In patients receiving saxagliptin, reductions in HbA1c at Week 16 were maintained to Week 52, while switching from placebo to saxagliptin resulted in a similar reduction in HbA1c. The incidence of hypoglycemia was not markedly increased with saxagliptin versus placebo in the double-blind period and did not increase substantially during the open-label extension period. The efficacy and safety of saxagliptin was similar between the elderly and non-elderly patient groups. Adding saxagliptin to ongoing insulin therapy improved glycemic control and was well tolerated in Japanese patients with type 2 diabetes.

  7. Histologic Evidence of New Collagen Formulation Using Platelet Rich Plasma in Skin Rejuvenation: A Prospective Controlled Clinical Study

    OpenAIRE

    Abuaf, Ozlem Karabudak; Yildiz, Hamza; Baloglu, H?seyin; Bilgili, Memet Ersan; Simsek, Hasan Aktug; Dogan, Bilal

    2016-01-01

    Background Platelet-rich plasma (PRP) is an autologous concentration of human platelets contained in a small volume of plasma and has recently been shown to accelerate rejuvenate aging skin by various growth factors and cell adhesion molecules. Objective This study was conducted to evaluate the efficacy and safety of intradermal injection of PRP in the human facial rejuvenation. Methods This study was a prospective, single-center, single-dose, open-label, non-randomized controlled clinical st...

  8. Peginterferon alfa-2b and weight-based or flat-dose ribavirin in chronic hepatitis C patients: a randomized trial.

    Science.gov (United States)

    Jacobson, Ira M; Brown, Robert S; Freilich, Bradley; Afdhal, Nezam; Kwo, Paul Y; Santoro, John; Becker, Scott; Wakil, Adil E; Pound, David; Godofsky, Eliot; Strauss, Robert; Bernstein, David; Flamm, Steven; Pauly, Mary Pat; Mukhopadhyay, Pabak; Griffel, Louis H; Brass, Clifford A

    2007-10-01

    This prospective, multicenter, community-based and academic-based, open-label, investigator-initiated, U.S. study evaluated efficacy and safety of pegylated interferon (PEG-IFN) alfa-2b plus a flat or weight-based dose of ribavirin (RBV) in adults with chronic hepatitis C. Patients (n = 5027) were randomly assigned to receive PEG-IFN alfa-2b 1.5 microg/kg/week plus flat-dose (800 mg/day) or weight-based (800-1400 mg/day) RBV for 48 weeks (patients with genotype 1, 4, 5, or 6) and for 24 or 48 weeks (genotype 2/3 patients). Primary end point was sustained virologic response (undetectable [<125 IU/mL] serum hepatitis C virus RNA at 24-week follow-up). Sustained virologic response, but not end-of-treatment, rates were significantly higher with weight-based than with flat-dose RBV (44.2% versus 40.5%; P = 0.008). Sustained virologic response rates by intention-to-treat analysis were 34.0% and 28.9%, respectively, in genotype 1 patients (P = 0.005) and 31.2% and 26.7%, respectively, in genotype 1 patients with high baseline viral load (P = 0.056). In genotype 2/3 patients, rates were not significantly different (61.8% and 59.5%, respectively) regardless of treatment duration. Besides greater hemoglobin reductions with weight-based RBV, safety profiles were similar across RBV dosing groups, including the 1400-mg/day group. PEG-IFN alfa-2b plus weight-based RBV is more effective than flat-dose RBV, particularly in genotype 1 patients, providing equivalent efficacy across all weight groups. RBV 1400 mg/day is appropriate for patients 105 to 125 kg. For genotype 2/3 patients, 24 weeks of treatment with flat-dose RBV is adequate; no evidence of additional benefit of extending treatment to 48 weeks was demonstrated.

  9. Open-label study of donepezil in traumatic brain injury.

    Science.gov (United States)

    Masanic, C A; Bayley, M T; VanReekum, R; Simard, M

    2001-07-01

    To determine preliminarily whether donepezil will improve memory, behavior, and global function after chronic traumatic brain injury (TBI). Sixteen-week open-label study. Outpatient TBI rehabilitation program. Four patients with chronic, severe TBI. Donepezil 5mg daily for 8 weeks followed by 10mg daily for 4 weeks. Memory measures included the Rey Auditory Verbal Learning Test (RAVLT), the Complex Figure Test (CFT), items from the Rivermead Behavioural Memory Test (RBMT), and a semantic fluency task. The Neuropsychiatric Inventory (NPI) evaluated behavior and affect. Function was assessed by using the FIM instrument and a clinical global impression of change. On the RAVLT, the mean scores for learning and short- and long-term recall improved by 0.4, 1.04, and.83 standard deviations (SDs) above baseline, respectively. On the CFT, the mean scores for short-term recall and long-term recall improved by 1.56 and 1.38 SDs above baseline, respectively. A positive trend was observed on the RBMT and on the NPI subscales. Donepezil may improve some aspects of memory and behavior in persons with chronic TBI. Randomized clinical trials are required to support these preliminary findings. Copyright 2001 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation

  10. Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study.

    Science.gov (United States)

    Carhart-Harris, Robin L; Bolstridge, Mark; Rucker, James; Day, Camilla M J; Erritzoe, David; Kaelen, Mendel; Bloomfield, Michael; Rickard, James A; Forbes, Ben; Feilding, Amanda; Taylor, David; Pilling, Steve; Curran, Valerie H; Nutt, David J

    2016-07-01

    Psilocybin is a serotonin receptor agonist that occurs naturally in some mushroom species. Recent studies have assessed the therapeutic potential of psilocybin for various conditions, including end-of-life anxiety, obsessive-compulsive disorder, and smoking and alcohol dependence, with promising preliminary results. Here, we aimed to investigate the feasibility, safety, and efficacy of psilocybin in patients with unipolar treatment-resistant depression. In this open-label feasibility trial, 12 patients (six men, six women) with moderate-to-severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin (10 mg and 25 mg, 7 days apart) in a supportive setting. There was no control group. Psychological support was provided before, during, and after each session. The primary outcome measure for feasibility was patient-reported intensity of psilocybin's effects. Patients were monitored for adverse reactions during the dosing sessions and subsequent clinic and remote follow-up. Depressive symptoms were assessed with standard assessments from 1 week to 3 months after treatment, with the 16-item Quick Inventory of Depressive Symptoms (QIDS) serving as the primary efficacy outcome. This trial is registered with ISRCTN, number ISRCTN14426797. Psilocybin's acute psychedelic effects typically became detectable 30-60 min after dosing, peaked 2-3 h after dosing, and subsided to negligible levels at least 6 h after dosing. Mean self-rated intensity (on a 0-1 scale) was 0·51 (SD 0·36) for the low-dose session and 0·75 (SD 0·27) for the high-dose session. Psilocybin was well tolerated by all of the patients, and no serious or unexpected adverse events occurred. The adverse reactions we noted were transient anxiety during drug onset (all patients), transient confusion or thought disorder (nine patients), mild and transient nausea (four patients), and transient headache (four patients). Relative to baseline, depressive symptoms were markedly reduced 1

  11. Change from subcutaneous to intravenous abatacept and back in patients with rheumatoid arthritis as simulation of a vacation: a prospective phase IV, open-label trial (A-BREAK).

    Science.gov (United States)

    Mueller, Ruediger B; Gengenbacher, Michael; Richter, Symi; Dudler, Jean; Möller, Burkhard; von Kempis, Johannes

    2016-04-14

    Vacation can present a major problem to patients with rheumatoid arthritis (RA) treated with weekly subcutaneous biologics, including subcutaneous (SC) abatacept. Therefore, the replacement of four SC doses of abatacept by a single dose of intravenous (IV) abatacept may present an acceptable alternative to cover a 4-week interval needed for vacations. In the study presented, we analyzed the efficacy and safety of this intervention followed by a switch back to SC abatacept after 4 weeks. This open-label, prospective, single-arm, 24-week trial recruited patients with established RA in low disease activity (LDA) or in remission on treatment with SC abatacept for at least 3 months to receive a single dose of IV abatacept (baseline) followed by a break of 4 weeks and then continuation of weekly SC abatacept from day 28 on. Disease-modifying anti-rheumatic drug (DMARD)-inadequate or biologic-inadequate responders (or both) were included. The baseline characteristics of the 49 patients (per protocol) were typical for a cohort of RA patients with established disease (mean disease duration of 8.31 years) in LDA under treatment with synthetic DMARDs and a biologic. Two patients (one flare and one patient decision) dropped out of the study. The proportions of patients with disease activity score in 28 joints (DAS-28) of not more than 3.2 at day 28 were 93.9 % (95 % confidence interval (CI) 83.5-97.9) and 93.6 % (95 % CI 82.8-97.8) at the end of the study (day 168). The average DAS-28 values were 1.74 (standard deviation (SD) ± 0.72) at baseline, 2.03 (SD ± 1.03) at day 28, and 1.96 (SD ± 0.92) at the end of the study (day 168). Pre-exposure to IV abatacept and having failed methotrexate or anti-tumor necrosis factor (anti-TNF) did not influence the average DAS-28 or the proportion of patients maintaining LDA over time. The average health assessment questionnaire disability index (HAQ-DI) was stable throughout the study. Adverse events (AEs) occurred in

  12. Improved Lipid Profile Associated with Daily Consumption of Tri-Sura-Phon in Healthy Overweight Volunteers: An Open-Label, Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Sirigoon Kuamsub

    2017-01-01

    Full Text Available Tri-Sura-Phon (TSP, a traditional Thai polyherbal formula renowned for its rejuvenating properties, is commonly used as a blood tonic. It comprises Cinnamomum bejolghota, Cinnamomum parthenoxylon, and Aquilaria crassna. The aim of this study is to evaluate the beneficial properties of TSP tea consumption on blood glucose regulation and serum lipid profiles of healthy overweight volunteers. This open-label, randomized controlled trial was conducted in 70 healthy overweight adults. Two groups of 35 subjects took a TSP infusion or a placebo (cornstarch twice daily for 8 weeks. The blood glucose regulation, serum lipid profiles, BMI, and liver function tests of the subjects were determined at the baseline, 4th week, and endpoint (8th week. Significant decreases in the average fasting levels of total cholesterol (p=0.013, triglyceride (p=0.001, and low-density lipoprotein (LDL, p=0.017 were observed in the TSP group at the 8th week compared to those at the baseline. The average HDL level in the TSP group at the beginning of the study was 65.2 mg/dL, and it increased significantly (p=0.005 to 72.4 mg/dL after 8 weeks of TSP intake. This study showed that the intake of TSP tea as an antioxidant-rich beverage might be safe and improve lipid profiles in overweight adults.

  13. Improved Lipid Profile Associated with Daily Consumption of Tri-Sura-Phon in Healthy Overweight Volunteers: An Open-Label, Randomized Controlled Trial

    Science.gov (United States)

    Kuamsub, Sirigoon; Singthong, Pariyaphat; Chanthasri, Wipawee; Chobngam, Nicharee; Sangkaew, Warissara; Hemdecho, Sasithorn; Kaewmanee, Thammarat

    2017-01-01

    Tri-Sura-Phon (TSP), a traditional Thai polyherbal formula renowned for its rejuvenating properties, is commonly used as a blood tonic. It comprises Cinnamomum bejolghota, Cinnamomum parthenoxylon, and Aquilaria crassna. The aim of this study is to evaluate the beneficial properties of TSP tea consumption on blood glucose regulation and serum lipid profiles of healthy overweight volunteers. This open-label, randomized controlled trial was conducted in 70 healthy overweight adults. Two groups of 35 subjects took a TSP infusion or a placebo (cornstarch) twice daily for 8 weeks. The blood glucose regulation, serum lipid profiles, BMI, and liver function tests of the subjects were determined at the baseline, 4th week, and endpoint (8th week). Significant decreases in the average fasting levels of total cholesterol (p = 0.013), triglyceride (p = 0.001), and low-density lipoprotein (LDL, p = 0.017) were observed in the TSP group at the 8th week compared to those at the baseline. The average HDL level in the TSP group at the beginning of the study was 65.2 mg/dL, and it increased significantly (p = 0.005) to 72.4 mg/dL after 8 weeks of TSP intake. This study showed that the intake of TSP tea as an antioxidant-rich beverage might be safe and improve lipid profiles in overweight adults. PMID:28484502

  14. Improved Lipid Profile Associated with Daily Consumption of Tri-Sura-Phon in Healthy Overweight Volunteers: An Open-Label, Randomized Controlled Trial.

    Science.gov (United States)

    Kuamsub, Sirigoon; Singthong, Pariyaphat; Chanthasri, Wipawee; Chobngam, Nicharee; Sangkaew, Warissara; Hemdecho, Sasithorn; Kaewmanee, Thammarat; Chusri, Sasitorn

    2017-01-01

    Tri-Sura-Phon (TSP), a traditional Thai polyherbal formula renowned for its rejuvenating properties, is commonly used as a blood tonic. It comprises Cinnamomum bejolghota , Cinnamomum parthenoxylon , and Aquilaria crassna . The aim of this study is to evaluate the beneficial properties of TSP tea consumption on blood glucose regulation and serum lipid profiles of healthy overweight volunteers. This open-label, randomized controlled trial was conducted in 70 healthy overweight adults. Two groups of 35 subjects took a TSP infusion or a placebo (cornstarch) twice daily for 8 weeks. The blood glucose regulation, serum lipid profiles, BMI, and liver function tests of the subjects were determined at the baseline, 4th week, and endpoint (8th week). Significant decreases in the average fasting levels of total cholesterol ( p = 0.013), triglyceride ( p = 0.001), and low-density lipoprotein (LDL, p = 0.017) were observed in the TSP group at the 8th week compared to those at the baseline. The average HDL level in the TSP group at the beginning of the study was 65.2 mg/dL, and it increased significantly ( p = 0.005) to 72.4 mg/dL after 8 weeks of TSP intake. This study showed that the intake of TSP tea as an antioxidant-rich beverage might be safe and improve lipid profiles in overweight adults.

  15. Tamoxifen Forms DNA Adducts In Human Colon After Administration Of A Single [14C]-Labeled Therapeutic Dose.

    Energy Technology Data Exchange (ETDEWEB)

    Brown, K; Tompkins, E M; Boocock, D J; Martin, E A; Farmer, P B; Turteltaub, K W; Ubick, E; Hemingway, D; Horner-Glister, E; White, I H

    2007-05-23

    Tamoxifen is widely prescribed for the treatment of breast cancer and is also licensed in the U.S. for the prevention of this disease. However, tamoxifen therapy is associated with an increased occurrence of endometrial cancer in women and there is also evidence that it may elevate the risk of colorectal cancer. The underlying mechanisms responsible for tamoxifen-induced carcinogenesis in women have not yet been elucidated but much interest has focussed on the role of DNA adduct formation. We investigated the propensity of tamoxifen to bind irreversibly to colorectal DNA when given to ten women as a single [{sup 14}C]-labeled therapeutic (20 mg) dose, {approx}18 h prior to undergoing colon resections. Using the sensitive technique of accelerator mass spectrometry, coupled with HPLC separation of enzymatically digested DNA, a peak corresponding to authentic dG-N{sup 2}-tamoxifen adduct was detected in samples from three patients, at levels ranging from 1-7 adducts/10{sup 9} nucleotides. No [{sup 14}C]-radiolabel associated with tamoxifen or its major metabolites was detected. The presence of detectable CYP3A4 protein in all colon samples suggests this tissue has the potential to activate tamoxifen to {alpha}-hydroxytamoxifen, in addition to that occurring in the systemic circulation, and direct interaction of this metabolite with DNA could account for the binding observed. Although the level of tamoxifeninduced damage displayed a degree of inter-individual variability, when present it was {approx}10-100 times higher than that reported for other suspect human colon carcinogens such as PhIP. These findings provide a mechanistic basis through which tamoxifen could increase the incidence of colon cancers in women.

  16. Pharmacokinetics of diclofenac in pigs after intramuscular administration of a single dose

    OpenAIRE

    Pejčić Zorica; Pokrajac Milena; Jezdimirović Milanka

    2006-01-01

    The pharmacokinetics of diclofenac was studied in 10 clinically normal male Yorkshire pigs, following intramuscular (i.m) administration of a single dose of diclofenac-sodium (2.5 mg/kg body weight). Diclofenac serum concentrations were determined by high pressure- liquid-chromatography (HPLC), with UV detection (226 nm). Following i.m. administration all individual diclofenac serum levels best fitted the one-compartment open model for extravascular administration. The maximal diclofenac seru...

  17. Probiotics in diverticular disease of the colon: an open label study.

    Science.gov (United States)

    Lamiki, Pepu; Tsuchiya, Junji; Pathak, Surajit; Okura, Ruichi; Solimene, Umberto; Jain, Shalini; Kawakita, Shichiro; Marotta, Francesco

    2010-03-01

    To investigate the effectiveness and safety of a symbiotic mixture in preventing recurrence of constipation-related abdominal pain in patients with uncomplicated diverticular disease of the colon. Forty-six consecutive patients (10 men, 36 women, mean age 62.5 years, range 49 to 77 years), previously affected by symptomatic uncomplicated diverticular disease of the colon, were enrolled in a 6-month follow-up study in a prospective, randomized, open-label study. The following symptoms were assessed at entry and through follow-up by using a quantitative scale: constipation, diarrhoea and abdominal pain. After recruitment, the patients were assigned to the following treatment: SCM-III symbiotic mixture, 10 ml three times a day. The colonization of ingested Lactobacillus acidophilus 145 and Bifidobacterium spp. 420 was assessed by species-specific PCR. Forty-five patients completed the study (97%). Thirty-one patients (68%) were still symptom free after the 6th month of treatment. Treatment with SCM-III was regarded as "effective" or "very effective" in more than 78% of the patients altogether (pdiverticular disease of the colon, especially in those patients with constipation-predominant features.

  18. An open-label Optional Titration Trial to Evaluate the Efficacy ...

    African Journals Online (AJOL)

    An eight-week open-label optional titration trial to evaluate the efficacy, tolerability and safety of Valsartan 80 mg/ & 160 mg once daily was carried out in patients with mild to moderate essential hypertension at the Lagos University Teaching Hospital. There was a significant reduction in both systolic and diastolic blood ...

  19. Open-Label Trial of Atomoxetine Hydrochloride in Adults with ADHD

    Science.gov (United States)

    Johnson, Mats; Cederlund, Mats; Rastam, Maria; Areskoug, Bjorn; Gillberg, Christopher

    2010-01-01

    Background: While atomoxetine is an established treatment for attention-deficit/hyperactivity disorder in children, few studies have examined its efficacy for adults. Methods: Open-label trial of atomoxetine in 20 individuals with ADHD, aged 19-47 years, for 10 weeks, and a total of one year for responders. Results: Ten patients met primary…

  20. Ethosuximide for Essential Tremor: An Open-Label Trial

    OpenAIRE

    Gironell, Alexandre; Marin-Lahoz, Juan

    2016-01-01

    Background: T-type calcium channel activation has been postulated to underlie rhythmicity in the olivo-cerebellar system that is implicated in ET. Ethosuximide reduces T-type calcium currents and can suppress tremor in two animal models of ET. We explored the effects of ethosuximide in subjects with ET in an open-label trial using both clinical scales and accelerometric recordings measures. We initially planned to conduct the trial with 15 patients, but due to lack of efficacy and a high inci...

  1. Towards tracer dose reduction in PET studies: Simulation of dose reduction by retrospective randomized undersampling of list-mode data.

    Science.gov (United States)

    Gatidis, Sergios; Würslin, Christian; Seith, Ferdinand; Schäfer, Jürgen F; la Fougère, Christian; Nikolaou, Konstantin; Schwenzer, Nina F; Schmidt, Holger

    2016-01-01

    Optimization of tracer dose regimes in positron emission tomography (PET) imaging is a trade-off between diagnostic image quality and radiation exposure. The challenge lies in defining minimal tracer doses that still result in sufficient diagnostic image quality. In order to find such minimal doses, it would be useful to simulate tracer dose reduction as this would enable to study the effects of tracer dose reduction on image quality in single patients without repeated injections of different amounts of tracer. The aim of our study was to introduce and validate a method for simulation of low-dose PET images enabling direct comparison of different tracer doses in single patients and under constant influencing factors. (18)F-fluoride PET data were acquired on a combined PET/magnetic resonance imaging (MRI) scanner. PET data were stored together with the temporal information of the occurrence of single events (list-mode format). A predefined proportion of PET events were then randomly deleted resulting in undersampled PET data. These data sets were subsequently reconstructed resulting in simulated low-dose PET images (retrospective undersampling of list-mode data). This approach was validated in phantom experiments by visual inspection and by comparison of PET quality metrics contrast recovery coefficient (CRC), background-variability (BV) and signal-to-noise ratio (SNR) of measured and simulated PET images for different activity concentrations. In addition, reduced-dose PET images of a clinical (18)F-FDG PET dataset were simulated using the proposed approach. (18)F-PET image quality degraded with decreasing activity concentrations with comparable visual image characteristics in measured and in corresponding simulated PET images. This result was confirmed by quantification of image quality metrics. CRC, SNR and BV showed concordant behavior with decreasing activity concentrations for measured and for corresponding simulated PET images. Simulation of dose

  2. An open-label randomized controlled trial of low molecular weight heparin compared to heparin and coumadin for the treatment of venous thromboembolic events in children: the REVIVE trial.

    Science.gov (United States)

    Massicotte, Patricia; Julian, Jim A; Gent, Michael; Shields, Karen; Marzinotto, Velma; Szechtman, Barbara; Andrew, Maureen

    2003-01-25

    Venous thromboembolic events (VTE) are serious complications in children and for which the standard of care, unfractionated heparin followed by oral anticoagulation (UFH/OA), is problematic. The objective of REVIVE was to compare the efficacy and safety of a low molecular weight heparin (reviparin-sodium) to UFH/OA for the treatment of VTE in children. This multicenter, open-label study, with blinded central outcome adjudication, randomized patients with objectively confirmed VTE to receive either reviparin-sodium or UFH/OA. Dose adjustments were made using nomograms. The efficacy outcome was based on recurrent VTE and death due to VTE during the 3-month treatment period. The safety outcomes were major bleeding, minor bleeding and death. Due to slow patient accrual, REVIVE was closed prematurely. At 3 months, with reviparin-sodium, 2/36 patients (5.6%) had recurrent VTE or death compared to 4/40 patients (10.0%) receiving UFH/OA (odds ratio=0.53; 95% CI=(0.05, 4.00); Fisher's exact test: 2P=0.677). There were 7 major bleeds, 2/36 (5.6%) in the reviparin-sodium group and 5/40 (12.5%) in UFH/OA group (odds ratio=0.41; 95% confidence interval 0.04, 2.76); Fisher's exact test: P=0.435). There were 5 deaths during the study period, 1 (2.8%) in the reviparin-sodium group and 4 (10.0%) in the UFH/OA group. All five deaths were unrelated to VTE but one was due to an intracranial hemorrhage in the UFH/OA group. Although limited by small sample size, REVIVE provides valuable information on the incidence of recurrent VTE, major bleeding and problematic issues associated with therapy of VTE in children.

  3. Administration of single-dose GnRH agonist in the luteal phase in ICSI cycles: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Oliveira João

    2010-09-01

    Full Text Available Abstract Background The effects of gonadotrophin-releasing hormone agonist (GnRH-a administered in the luteal phase remains controversial. This meta-analysis aimed to evaluate the effect of the administration of a single-dose of GnRH-a in the luteal phase on ICSI clinical outcomes. Methods The research strategy included the online search of databases. Only randomized studies were included. The outcomes analyzed were implantation rate, clinical pregnancy rate (CPR per transfer and ongoing pregnancy rate. The fixed effects model was used for odds ratio. In all trials, a single dose of GnRH-a was administered at day 5/6 after ICSI procedures. Results All cycles presented statistically significantly higher rates of implantation (P Conclusions These findings demonstrate that the luteal-phase single-dose GnRH-a administration can increase implantation rate in all cycles and CPR per transfer and ongoing pregnancy rate in cycles with GnRH antagonist ovarian stimulation protocol. Nevertheless, by considering the heterogeneity between the trials, it seems premature to recommend the use of GnRH-a in the luteal phase. Additional randomized controlled trials are necessary before evidence-based recommendations can be provided.

  4. Impact of food labelling systems on food choices and eating behaviours: a systematic review and meta-analysis of randomized studies.

    Science.gov (United States)

    Cecchini, M; Warin, L

    2016-03-01

    Food labels are considered a crucial component of strategies tackling unhealthy diets and obesity. This study aims at assessing the effectiveness of food labelling in increasing the selection of healthier products and in reducing calorie intake. In addition, this study compares the relative effectiveness of traffic light schemes, Guideline Daily Amount and other food labelling schemes. A comprehensive set of databases were searched to identify randomized studies. Studies reporting homogeneous outcomes were pooled together and analysed through meta-analyses. Publication bias was evaluated with a funnel plot. Food labelling would increase the amount of people selecting a healthier food product by about 17.95% (confidence interval: +11.24% to +24.66%). Food labelling would also decrease calorie intake/choice by about 3.59% (confidence interval: -8.90% to +1.72%), but results are not statistically significant. Traffic light schemes are marginally more effective in increasing the selection of healthier options. Other food labels and Guideline Daily Amount follow. The available evidence did not allow studying the effects of single labelling schemes on calorie intake/choice. Findings of this study suggest that nutrition labelling may be an effective approach to empowering consumers in choosing healthier products. Interpretive labels, as traffic light labels, may be more effective. © 2015 World Obesity.

  5. Ethosuximide for Essential Tremor: An Open-Label Trial

    Science.gov (United States)

    Gironell, Alexandre; Marin-Lahoz, Juan

    2016-01-01

    Background T-type calcium channel activation has been postulated to underlie rhythmicity in the olivo-cerebellar system that is implicated in ET. Ethosuximide reduces T-type calcium currents and can suppress tremor in two animal models of ET. We explored the effects of ethosuximide in subjects with ET in an open-label trial using both clinical scales and accelerometric recordings measures. We initially planned to conduct the trial with 15 patients, but due to lack of efficacy and a high incidence of adverse effects, the trial was stopped after seven patients had participated. Methods Seven patients diagnosed with ET were included in the study. The ethosuximide dose was 500 mg daily (BID). The main outcome measures were: 1) tremor clinical rating scale (TCRS) score, 2) accelerometric recordings, and 3) self-reported disability scale score. Results Five patients completed the study, and two dropped out due to adverse effects. There were no significant changes in clinical scores in motor task performance (TCRS 1+2), daily living activities (TCRS 3), or in the patients’ subjective assessment (TCRS 4) and global appraisal. There were no differences observed for accelerometry data or disability scale scores. Anxiety, nervousness, headache, and dizziness were reported by two patients while on ethosuximide, causing them to stop the trial. No patient preferred to continue ethosuximide treatment. Discussion The results of our exploratory study suggest that ethosuximide is not an effective treatment for ET. PMID:27625899

  6. Ethosuximide for Essential Tremor: An Open-Label Trial

    Directory of Open Access Journals (Sweden)

    Alexandre Gironell

    2016-07-01

    Full Text Available Background: T-type calcium channel activation has been postulated to underlie rhythmicity in the olivo-cerebellar system that is implicated in ET. Ethosuximide reduces T-type calcium currents and can suppress tremor in two animal models of ET. We explored the effects of ethosuximide in subjects with ET in an open-label trial using both clinical scales and accelerometric recordings measures. We initially planned to conduct the trial with 15 patients, but due to lack of efficacy and a high incidence of adverse effects, the trial was stopped after seven patients had participated. Methods: Seven patients diagnosed with ET were included in the study. The ethosuximide dose was 500 mg daily (BID. The main outcome measures were: 1 tremor clinical rating scale (TCRS score, 2 accelerometric recordings, and 3 self-reported disability scale score. Results: Five patients completed the study, and two dropped out due to adverse effects. There were no significant changes in clinical scores in motor task performance (TCRS 1+2, daily living activities (TCRS 3, or in the patients’ subjective assessment (TCRS 4 and global appraisal. There were no differences observed for accelerometry data or disability scale scores. Anxiety, nervousness, headache, and dizziness were reported by two patients while on ethosuximide, causing them to stop the trial. No patient preferred to continue ethosuximide treatment. Discussion: The results of our exploratory study suggest that ethosuximide is not an effective treatment for ET.

  7. A Randomized Dose-Ranging Study of Neuropeptide Y in Patients with Posttraumatic Stress Disorder.

    Science.gov (United States)

    Sayed, Sehrish; Van Dam, Nicholas T; Horn, Sarah R; Kautz, Marin M; Parides, Michael; Costi, Sara; Collins, Katherine A; Iacoviello, Brian; Iosifescu, Dan V; Mathé, Aleksander A; Southwick, Steven M; Feder, Adriana; Charney, Dennis S; Murrough, James W

    2018-01-01

    Anxiety and trauma-related disorders are among the most prevalent and disabling medical conditions in the United States, and posttraumatic stress disorder in particular exacts a tremendous public health toll. We examined the tolerability and anxiolytic efficacy of neuropeptide Y administered via an intranasal route in patients with posttraumatic stress disorder. Twenty-six individuals were randomized in a cross-over, single ascending dose study into 1 of 5 cohorts: 1.4 mg (n=3), 2.8 mg (n=6), 4.6 mg (n=5), 6.8 mg (n=6), and 9.6 mg (n=6). Each individual was dosed with neuropeptide Y or placebo on separate treatment days 1 week apart in random order under double-blind conditions. Assessments were conducted at baseline and following a trauma script symptom provocation procedure subsequent to dosing. Occurrence of adverse events represented the primary tolerability outcome. The difference between treatment conditions on anxiety as measured by the Beck Anxiety Inventory and the State-Trait Anxiety Inventory immediately following the trauma script represented efficacy outcomes. Twenty-four individuals completed both treatment days. Neuropeptide Y was well tolerated up to and including the highest dose. There was a significant interaction between treatment and dose; higher doses of neuropeptide Y were associated with a greater treatment effect, favoring neuropeptide Y over placebo on Beck Anxiety Inventory score (F1,20=4.95, P=.038). There was no significant interaction for State-Trait Anxiety Inventory score. Our study suggests that a single dose of neuropeptide Y is well tolerated up to 9.6 mg and may be associated with anxiolytic effects. Future studies exploring the safety and efficacy of neuropeptide Y in stress-related disorders are warranted. The reported study is registered at: http://clinicaltrials.gov (ID: NCT01533519). © The Author(s) 2017. Published by Oxford University Press on behalf of CINP.

  8. Multicenter, Randomized, Open-Label, Phase III Trial of Decitabine Versus Patient Choice, With Physician Advice, of Either Supportive Care or Low-Dose Cytarabine for the Treatment of Older Patients With Newly Diagnosed Acute Myeloid Leukemia

    Science.gov (United States)

    Kantarjian, Hagop M.; Thomas, Xavier G.; Dmoszynska, Anna; Wierzbowska, Agnieszka; Mazur, Grzegorz; Mayer, Jiri; Gau, Jyh-Pyng; Chou, Wen-Chien; Buckstein, Rena; Cermak, Jaroslav; Kuo, Ching-Yuan; Oriol, Albert; Ravandi, Farhad; Faderl, Stefan; Delaunay, Jacques; Lysák, Daniel; Minden, Mark; Arthur, Christopher

    2012-01-01

    Purpose This multicenter, randomized, open-label, phase III trial compared the efficacy and safety of decitabine with treatment choice (TC) in older patients with newly diagnosed acute myeloid leukemia (AML) and poor- or intermediate-risk cytogenetics. Patients and Methods Patients (N = 485) age ≥ 65 years were randomly assigned 1:1 to receive decitabine 20 mg/m2 per day as a 1-hour intravenous infusion for five consecutive days every 4 weeks or TC (supportive care or cytarabine 20 mg/m2 per day as a subcutaneous injection for 10 consecutive days every 4 weeks). The primary end point was overall survival (OS); the secondary end point was the complete remission (CR) rate plus the CR rate without platelet recovery (CRp). Adverse events (AEs) were recorded. Results The primary analysis with 396 deaths (81.6%) showed a nonsignificant increase in median OS with decitabine (7.7 months; 95% CI, 6.2 to 9.2) versus TC (5.0 months; 95% CI, 4.3 to 6.3; P = .108; hazard ratio [HR], 0.85; 95% CI, 0.69 to 1.04). An unplanned analysis with 446 deaths (92%) indicated the same median OS (HR, 0.82; 95% CI, 0.68 to 0.99; nominal P = .037). The CR rate plus CRp was 17.8% with decitabine versus 7.8% with TC (odds ratio, 2.5; 95% CI, 1.4 to 4.8; P = .001). AEs were similar for decitabine and cytarabine, although patients received a median of four cycles of decitabine versus two cycles of TC. The most common drug-related AEs with decitabine were thrombocytopenia (27%) and neutropenia (24%). Conclusion In older patients with AML, decitabine improved response rates compared with standard therapies without major differences in safety. An unplanned survival analysis showed a benefit for decitabine, which was not observed at the time of the primary analysis. PMID:22689805

  9. Staggering the dose of sugammadex lowers risks for severe emergence cough: a randomized control trial.

    Science.gov (United States)

    P S, Loh; Miskan, M M; Y Z, Chin; Zaki, R A

    2017-10-11

    Cough on emergence has been reported as a common adverse reaction with sugammadex reversal. We investigated if staggering the dose of sugammadex will reduce emergence cough in a single-center, randomized, double-blinded study. A hundred and twenty ASA 1-3 adults were randomly reversed with 1 mg/kg sugammadex prior to extubation followed by another 1 mg/kg immediately after extubation (staggered group), single dose of 2 mg/kg sugammadex (single bolus group) or neostigmine 0.02 mg/kg with glycopyrrolate (neostigmine group). We found 70% of patients (n = 28) reversed with single boluses of sugammadex had Grade 3 emergence cough compared to 12.5% (n = 5) in the staggered sugammadex group and 17.5% (n = 7) in the neostigmine group (p sugammadex group (n = 14, 35%, p = 0.005). On the other hand, staggering sugammadex lowered risks of developing severe cough (RR 0.2, p sugammadex group and control given neostigmine. In terms of timing, there was no delay in time taken from discontinuing anesthetic agents to reversal and extubation if sugammadex was staggered (emergence time 6.0 ± 3.2 s, p = 0.625 and reversal time 6.5 ± 3.5, p = 0.809). Staggering the dose of sugammadex for reversal will effectively decrease common emergence and early postoperative complications. ANZCTR Number ACTRN12616000116426 . Retrospectively registered on 2nd February 2016.

  10. Laparoscopic Complete Mesocolic Excision versus Open Complete Mesocolic Excision for Transverse Colon Cancer: Long-Term Survival Results of a Prospective Single Centre Non-Randomized Study.

    Science.gov (United States)

    Storli, Kristian Eeg; Eide, Geir Egil

    2016-01-01

    Laparoscopic complete mesocolic excision (CME) used in the treatment of transverse colon cancer has been questioned on the basis of the technical challenges. The aim of this study was to evaluate the medium- and long-term clinical and survival outcomes after laparoscopic and open CME for transverse colon cancer and to compare the 2 approaches. This study was a retrospective non-randomized study of patients with prospectively registered data on open and laparoscopic CME for transverse colon cancer tumour-node-metastasis stages I-III operated on between 2007 and 2014. This was a single-centre study in a community teaching hospital. A total of 56 patients with transverse colon cancer were included, excluding those with tumours in the colonic flexures. The outcome aims were 4-year time to recurrence (TTR) and cancer-specific survival (CSS). Morbidity was also measured. The 4-year TTR was 93.9% in the laparoscopic group and 91.3% in the open group (p = 0.71). The 4-year CSS was 97.0% in the laparoscopic group and 91.3% in the open group (p = 0.42). This was a prospective single-institution study with a small sample size. Results of the study suggest that the laparoscopic CME approach might be the preferred approach for transverse colon cancer, especially regarding its benefits in terms of short-term morbidity, length of stay and oncological outcome. © 2016 S. Karger AG, Basel.

  11. Immunogenicity of type 2 monovalent oral and inactivated poliovirus vaccines for type 2 poliovirus outbreak response: an open-label, randomised controlled trial.

    Science.gov (United States)

    Zaman, Khalequ; Estívariz, Concepción F; Morales, Michelle; Yunus, Mohammad; Snider, Cynthia J; Gary, Howard E; Weldon, William C; Oberste, M Steven; Wassilak, Steven G; Pallansch, Mark A; Anand, Abhijeet

    2018-03-20

    Monovalent type 2 oral poliovirus vaccine (mOPV2) and inactivated poliovirus vaccine (IPV) are used to respond to type 2 poliovirus outbreaks. We aimed to assess the effect of two mOPV2 doses on the type 2 immune response by varying the time interval between mOPV2 doses and IPV co-administration with mOPV2. We did a randomised, controlled, parallel, open-label, non-inferiority, inequality trial at two study clinics in Dhaka, Bangladesh. Healthy infants aged 6 weeks (42-48 days) at enrolment were randomly assigned (1:1:1:1) to receive two mOPV2 doses (each dose consisting of two drops [0·1 mL in total] of about 10 5 50% cell culture infectious dose of type 2 Sabin strain) at intervals of 1 week, 2 weeks, 4 weeks (standard or control group), or 4 weeks with IPV (0·5 mL of type 1 [Mahoney, 40 D-antigen units], type 2 [MEF-1, 8 D-antigen units], and type 3 [Saukett, 32 D-antigen units]) administered intramuscularly with the first mOPV2 dose. We used block randomisation, randomly selecting blocks of sizes four, eight, 12, or 16 stratified by study sites. We concealed randomisation assignment from staff managing participants in opaque, sequentially numbered, sealed envelopes. Parents and clinic staff were unmasked to assignment after the randomisation envelope was opened. Laboratory staff analysing sera were masked to assignment, but investigators analysing data and assessing outcomes were not. The primary outcome was type 2 immune response measured 4 weeks after mOPV2 administration. The primary modified intention-to-treat analysis included participants with testable serum samples before and after vaccination. A non-inferiority margin of 10% and p=0·05 (one-tailed) was used. This trial is registered at ClinicalTrials.gov, number NCT02643368, and is closed to accrual. Between Dec 7, 2015, and Jan 5, 2016, we randomly assigned 760 infants to receive two mOPV2 doses at intervals of 1 week (n=191), 2 weeks (n=191), 4 weeks (n=188), or 4 weeks plus IPV (n=190). Immune

  12. Encoding atlases by randomized classification forests for efficient multi-atlas label propagation.

    Science.gov (United States)

    Zikic, D; Glocker, B; Criminisi, A

    2014-12-01

    We propose a method for multi-atlas label propagation (MALP) based on encoding the individual atlases by randomized classification forests. Most current approaches perform a non-linear registration between all atlases and the target image, followed by a sophisticated fusion scheme. While these approaches can achieve high accuracy, in general they do so at high computational cost. This might negatively affect the scalability to large databases and experimentation. To tackle this issue, we propose to use a small and deep classification forest to encode each atlas individually in reference to an aligned probabilistic atlas, resulting in an Atlas Forest (AF). Our classifier-based encoding differs from current MALP approaches, which represent each point in the atlas either directly as a single image/label value pair, or by a set of corresponding patches. At test time, each AF produces one probabilistic label estimate, and their fusion is done by averaging. Our scheme performs only one registration per target image, achieves good results with a simple fusion scheme, and allows for efficient experimentation. In contrast to standard forest schemes, in which each tree would be trained on all atlases, our approach retains the advantages of the standard MALP framework. The target-specific selection of atlases remains possible, and incorporation of new scans is straightforward without retraining. The evaluation on four different databases shows accuracy within the range of the state of the art at a significantly lower running time. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Immunogenicity and safety of an adjuvanted herpes zoster subunit candidate vaccine in adults ≥ 50 years of age with a prior history of herpes zoster: A phase III, non-randomized, open-label clinical trial.

    Science.gov (United States)

    Godeaux, Olivier; Kovac, Martina; Shu, Daniel; Grupping, Katrijn; Campora, Laura; Douha, Martine; Heineman, Thomas C; Lal, Himal

    2017-05-04

    This phase III, non-randomized, open-label, multi-center study (NCT01827839) evaluated the immunogenicity and safety of an adjuvanted recombinant subunit herpes zoster (HZ) vaccine (HZ/su) in adults aged ≥ 50 y with prior physician-documented history of HZ. Participants (stratified by age: 50-59, 60-69 and ≥ 70 y) received 2 doses of HZ/su 2 months apart and were followed-up for another 12 months. Anti-glycoprotein E (gE) antibodies were measured by enzyme-linked immunosorbent assay before vaccination and 1 month after the second dose (Month 3). Solicited local and general adverse events (AEs) were recorded for 7 d and unsolicited AEs for 30 d after each vaccination. Serious AEs were recorded until study end. The primary immunogenicity objective was met if the lower limit of the 95% confidence interval (CI) of the vaccine response rate (VRR), defined as a 4-fold increase in anti-gE over baseline, at Month 3 was ≥ 60%. 96 participants (32/age group) were enrolled. The primary immunogenicity objective was met, as the VRR at Month 3 was 90.2% (95% CI: 81.7-95.7). Geometric mean anti-gE antibody concentrations at Month 3 were similar across age groups. 77.9% and 71.6% of participants reported local and general solicited AEs, respectively. The most frequent solicited AEs were pain at injection site, fatigue, headache, myalgia and shivering. The HZ/su vaccine was immunogenic in adults aged ≥ 50 y with a physician-documented history of HZ, and no safety concerns were identified.

  14. Cryo-imaging of fluorescently labeled single cells in a mouse

    Science.gov (United States)

    Steyer, Grant J.; Roy, Debashish; Salvado, Olivier; Stone, Meredith E.; Wilson, David L.

    2009-02-01

    We developed a cryo-imaging system to provide single-cell detection of fluorescently labeled cells in mouse, with particular applicability to stem cells and metastatic cancer. The Case cryoimaging system consists of a fluorescence microscope, robotic imaging positioner, customized cryostat, PC-based control system, and visualization/analysis software. The system alternates between sectioning (10-40 μm) and imaging, collecting color brightfield and fluorescent blockface image volumes >60GB. In mouse experiments, we imaged quantum-dot labeled stem cells, GFP-labeled cancer and stem cells, and cell-size fluorescent microspheres. To remove subsurface fluorescence, we used a simplified model of light-tissue interaction whereby the next image was scaled, blurred, and subtracted from the current image. We estimated scaling and blurring parameters by minimizing entropy of subtracted images. Tissue specific attenuation parameters were found [uT : heart (267 +/- 47.6 μm), liver (218 +/- 27.1 μm), brain (161 +/- 27.4 μm)] to be within the range of estimates in the literature. "Next image" processing removed subsurface fluorescence equally well across multiple tissues (brain, kidney, liver, adipose tissue, etc.), and analysis of 200 microsphere images in the brain gave 97+/-2% reduction of subsurface fluorescence. Fluorescent signals were determined to arise from single cells based upon geometric and integrated intensity measurements. Next image processing greatly improved axial resolution, enabled high quality 3D volume renderings, and improved enumeration of single cells with connected component analysis by up to 24%. Analysis of image volumes identified metastatic cancer sites, found homing of stem cells to injury sites, and showed microsphere distribution correlated with blood flow patterns. We developed and evaluated cryo-imaging to provide single-cell detection of fluorescently labeled cells in mouse. Our cryo-imaging system provides extreme (>60GB), micron

  15. Effect of treatment with single total-dose intravenous iron versus daily oral iron(III-hydroxide polymaltose on moderate puerperal iron-deficiency anemia

    Directory of Open Access Journals (Sweden)

    Iyoke CA

    2017-05-01

    Full Text Available Chukwuemeka Anthony Iyoke,1 Fausta Chioma Emegoakor,1 Euzebus Chinonye Ezugwu,1 Lucky Osaheni Lawani,2 Leonard Ogbonna Ajah,1 Jude Anazoeze Madu,3 Hyginus Uzo Ezegwui,1 Frank Okechukwu Ezugwu4 1Department of Obstetrics and Gynaecology, University of Nigeria, Enugu Campus, 2Department of Obstetrics and Gynaecology, Federal Teaching Hospital, Abakaliki, 3Department of Haematology, University of Nigeria, Nsukka, 4Department of Obstetrics and Gynaecology, College of Medicine, Enugu State University, Enugu, Nigeria Background: Iron-deficiency anemia is the most common nutritional cause of anemia in pregnancy and is often responsible for puerperal anemia. Puerperal anemia can impair postpartum maternal and neonatal well-being. Objective: To determine the effect of treatment of moderate puerperal iron-deficiency anemia using a single intravenous total-dose iron dextran versus daily single dose oral iron(III-hydroxide polymaltose. Methodology: A randomized controlled study in which postpartum women with moderate iron-deficiency anemia were randomized into treatment with either a single total-dose intravenous iron dextran or with daily single doses of oral iron(III-hydroxide polymaltose tablets for 6 weeks. Effects on hemoglobin concentration using either method were compared at 6 weeks postpartum. Analysis was per protocol using SPSS version 17 for windows. P-values ≤0.05 were considered significant. Results: Two hundred eighty-four women were recruited for the study: 142 women received single total dose intravenous infusion of iron dextran while 142 received daily oral iron(III-hydroxide polymaltose tablets. Approximately 84.0% (237/282 completed the study and were analyzed including 81% (115/142 of those randomized to injectable iron therapy compared to 85.9% (122/142 of those randomized to oral treatment. The proportions of women who had attained hemoglobin concentration of at least 10 g/dL by the 6 weeks postpartum visit did not differ

  16. Effect of thread embedding acupuncture for facial wrinkles and laxity: a single-arm, prospective, open-label study

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    Younghee Yun

    2017-12-01

    Full Text Available Background: There is a growing trend for patients to seek the least invasive treatments with less risk of complications and downtime for facial rejuvenation. Thread embedding acupuncture has become popular as a minimally invasive treatment. However, there is little clinical evidence in the literature regarding its effects. Methods: This single-arm, prospective, open-label study recruited participants who were women aged 40–59 years, with Glogau photoaging scale III–IV. Fourteen participants received thread embedding acupuncture one time and were measured before and after 1 week from the procedure. The primary outcome was a jowl to subnasale vertical distance. The secondary outcomes were facial wrinkle distances, global esthetic improvement scale, Alexiades–Armenakas laxity scale, and patient-oriented self-assessment scale. Results: Fourteen participants underwent thread embedding acupuncture alone, and 12 participants revisited for follow-up outcome measures. For the primary outcome measure, both jowls were elevated in vertical height by 1.87 mm (left and 1.43 mm (right. Distances of both melolabial and nasolabial folds showed significant improvement. In the Alexiades–Armenakas laxity scale, each evaluator evaluated for four and nine participants by 0.5 grades improved. In the global aesthetic improvement scale, improvement was graded as 1 and 2 in nine and five cases, respectively. The most common adverse events were mild bruising, swelling, and pain. However, adverse events occurred, although mostly minor and of short duration. Conclusion: In this study, thread embedding acupuncture showed clinical potential for facial wrinkles and laxity. However, further large-scale trials with a controlled design and objective measurements are needed. Keywords: polydioxanone, rejuvenation, rhytidoplasty, skin aging, thread embedding acupuncture

  17. Rationale and design of the VISION study: a randomized, open-label study to evaluate the long-term safety of vonoprazan as maintenance treatment in patients with erosive esophagitis

    Directory of Open Access Journals (Sweden)

    Uemura N

    2018-01-01

    Full Text Available Naomi Uemura,1 Yoshikazu Kinoshita,2 Ken Haruma,3 Takashi Yao,4 Ryoji Kushima,5 Tatsuhiro Kanoo6 1Department of Gastroenterology and Hepatology, National Center for Global Health and Medicine, Kohnodai Hospital, Chiba, Japan; 2Department of Gastroenterology and Hepatology, Faculty of Medicine, Shimane University, Shimane, Japan; 3Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center, Okayama, Japan; 4Department of Human Pathology, Juntendo University Graduate School of Medicine, Tokyo, Japan; 5Department of Clinical Laboratory Medicine, Shiga University of Medical Science Hospital, Shiga, Japan; 6Takeda Pharmaceutical Co., Ltd, Osaka, Japan Abstract: Erosive esophagitis (EE occurs when the epithelial mucosa is damaged due to gastric acid reflux, and the incidence of this disease is increasing in Japan due to changes in diet and lifestyle. The condition can be treated using proton pump inhibitors (PPIs that act by irreversibly blocking the H+,K+-ATPase responsible for acid secretion. Vonoprazan is a K+ competitive channel inhibitor, which reversibly and potently inhibits gastric acid secretion. However, long-term data on vonoprazan use are limited. The aim of the VISION trial is to investigate the long-term efficacy and safety of vonoprazan in comparison with the PPI lansoprazole. This randomized, multicenter, 5-year, open-label study has a planned recruitment of 195 participants (2:1 allocation vonoprazan:lansoprazole from 33 sites in Japan. The study comprises an 8-week “healing” phase (vonoprazan 20 mg or lansoprazole 30 mg p.o. and a 260-week “maintenance” phase (vonoprazan 10 mg or lansoprazole 15 mg. Safety populations in both phases are defined as participants who receive at least one dose of the study or control drug in the healing and maintenance phases, respectively. The full analysis set in both phases is defined as participants who are randomized and receive at least one dose of the study or

  18. D Semantic Labeling of ALS Data Based on Domain Adaption by Transferring and Fusing Random Forest Models

    Science.gov (United States)

    Wu, J.; Yao, W.; Zhang, J.; Li, Y.

    2018-04-01

    Labeling 3D point cloud data with traditional supervised learning methods requires considerable labelled samples, the collection of which is cost and time expensive. This work focuses on adopting domain adaption concept to transfer existing trained random forest classifiers (based on source domain) to new data scenes (target domain), which aims at reducing the dependence of accurate 3D semantic labeling in point clouds on training samples from the new data scene. Firstly, two random forest classifiers were firstly trained with existing samples previously collected for other data. They were different from each other by using two different decision tree construction algorithms: C4.5 with information gain ratio and CART with Gini index. Secondly, four random forest classifiers adapted to the target domain are derived through transferring each tree in the source random forest models with two types of operations: structure expansion and reduction-SER and structure transfer-STRUT. Finally, points in target domain are labelled by fusing the four newly derived random forest classifiers using weights of evidence based fusion model. To validate our method, experimental analysis was conducted using 3 datasets: one is used as the source domain data (Vaihingen data for 3D Semantic Labelling); another two are used as the target domain data from two cities in China (Jinmen city and Dunhuang city). Overall accuracies of 85.5 % and 83.3 % for 3D labelling were achieved for Jinmen city and Dunhuang city data respectively, with only 1/3 newly labelled samples compared to the cases without domain adaption.

  19. Open-label pilot study of memantine in the treatment of compulsive buying.

    Science.gov (United States)

    Grant, Jon E; Odlaug, Brian L; Mooney, Marc; O'Brien, Robert; Kim, Suck Won

    2012-05-01

    Although compulsive buying (CB) is relatively common, pharmacotherapy research for CB is limited. Memantine, an N-methyl-D-aspartate receptor antagonist, appears to reduce glutamate excitability and improve impulsive behaviors, suggesting it may help individuals with CB. Nine patients (8 females) with CB were enrolled in a 10-week open-label treatment study of memantine (dose ranging from 10 to 30 mg/d). Participants were enrolled from December 2008 until May 2010. The primary outcome measure was change from baseline to study endpoint on the Yale-Brown Obsessive Compulsive Scale-Shopping Version (Y-BOCS-SV). Of the 9 participants, 8 (88.9%) completed the 10-week study. Y-BOCS-SV scores decreased from a mean of 22.0 ± 1.3 at baseline to 11.0 ± 5.3 at endpoint (P impulsive buying and improvements on cognitive tasks of impulsivity. In addition, the medication was well-tolerated. These findings suggest that pharmacologic manipulation of the glutamate system may target the impulsive behavior underlying CB. Placebo-controlled, double-blind studies are warranted in order to confirm these preliminary findings in a controlled design.

  20. Vaxchora: A Single-Dose Oral Cholera Vaccine.

    Science.gov (United States)

    Cabrera, Adriana; Lepage, Jayne E; Sullivan, Karyn M; Seed, Sheila M

    2017-07-01

    To review trials evaluating the efficacy and safety of Vaxchora, a reformulated, single-dose, oral, lyophilized Vibrio cholerae CVD 103-HgR vaccine for the prevention of travel-related cholera caused by V cholerae serogroup O1. A literature search was conducted using MEDLINE (1946 to January week 3, 2017) and EMBASE (1996 to 2017 week 3). Keywords included oral cholera vaccine, single-dose, Vaxchora, and CVD 103-HgR. Limits included human, clinical trials published in English since 2010. ClinicalTrials.gov was used as a source for unpublished data. Additional data sources were obtained through bibliographic review of selected articles. Studies that addressed the safety and efficacy of Vaxchora, the reformulated, single-dose oral CVD 103-HgR cholera vaccine, were selected for analysis. Approval of Vaxchora, was based on efficacy of the vaccine in human trials demonstrating 90.3% protection among those challenged with V cholerae 10 days after vaccination and in immunogenicity studies with 90% systemic vibriocidal antibody conversion at 6 months after a single-dose of vaccine. Tolerability was acceptable, with the most common adverse effects reported to be fatigue, headache, and abdominal pain. Vaxchora is the only FDA-approved, single-dose oral vaccine for the prevention of cholera caused by V cholerae serogroup O1 in adult travelers from the United States going to cholera-affected areas. Safety and efficacy has not been established in children, immunocompromised persons, and pregnant or breastfeeding women or those living in cholera-endemic areas.

  1. Low-dose ketoconazole-fluconazole combination versus fluconazole in single doses for the treatment of vaginal candidiasis

    Directory of Open Access Journals (Sweden)

    Jan Susilo

    2011-08-01

    Full Text Available Background: Vaginal candidiasis (VC is one of the most common fungal diseases. Candida albicans is the most common causative fungus and has been isolated from more than 80% of specimens obtained from women with VC. Ketoconazole is the first orally active antifungal, the dosage for VC is 200 mg twice daily for 5 days. Fluconazole is the newer oral antifungal, its dosage for VC is a single oral dose of 150 mg. Since fluconazole 150 mg is considerably expensive, a single dose of 100 mg ketoconazole and 40 mg fluconazole in combination has been tested for the treatment of VC. The results showed that from 11 women with confirmed VC, 1-2 weeks after drug administration, the mycological culture was negative in 8 women, positive in 1 woman, and 2 woman lost to follow-up. This promising result led to the present study with the objective to confirm the efficacy and safety of the above combination in a formal clinical trial.Methods: A total of 165 female patients, aged 18 years or older, with the diagnosis of VC from clinical symptoms (pruritus or burning or excessive discharge and positive microscopic smear (pseudohyphae and/or yeast cells were randomized to receive a single dose of either keto-fluco combination (n = 85 or fluconazole (n = 80, and returnedfor follow-up visit on day 8.Results: Among these patients, 39 patients had negative baseline culture, leaving 126 patients eligible for efficacy evaluation. The mycological eradication in the keto-fluco group was 74.5% (41 patients from a total of 55 patients with available mycological culture, while that in the fluconazole group was 70.2% (40 patients from 57 patients with available culture and this difference was not significant. The clinical favorable response (clinical cure and clinical improvement in the keto-fluco arm (n = 60 was 98.3%, while that in the fluconazole group (n = 66 was 100%. Adverse events were found in 5 patients, 3 patients in the keto-fluco group (3/85 = 3.5% and 2

  2. The effects of A single dose of gamma-rays applied on the head on behavior of rats in Morris's water maze and in the open field test

    International Nuclear Information System (INIS)

    Smajda, B.; Kiskova, J.; Lievajova, K.; Capicikova, M.

    2006-01-01

    The effects of a sublethal dose of gamma-rays applied on the head on selected behavioral parameters were investigated in this study. Adult male Sprague-Dowley rats (n=9) were irradiated with a single dose of 20 Gy of gamma-rays from a 60 Co radiation source. The irradiated animals as well as sham-irradiated controls were tested daily in Morris water maze (MWM) (2 sessions per day) and in the open field test. The ability of spatial learning given by latency time to find the hidden platform was followed in MWM. The horizontal and vertical locomotion, the number of crossings of the center of the field and the washing behavior were recorded during an 8-minute test in the open field. The results obtained show, that radiation didn't altered significantly the dynamic of learning in MWM during the experiment. The level of horizontal and vertical locomotory activity in open field was lower in irradiated group in comparison with controls. The number of the crossings of the field's center, related to the level of anxiozity of animals was non-significantly lower in irradiated animals, whereas no differences in number of washing between both groups were detected. The results point to differences in radiosensitivity in various behavioral parameters in rats, maybe due to different level of their control and coordination in CNS. (authors)

  3. Dose De-escalation of Intrapleural Tissue Plasminogen Activator Therapy for Pleural Infection. The Alteplase Dose Assessment for Pleural Infection Therapy Project.

    Science.gov (United States)

    Popowicz, Natalia; Bintcliffe, Oliver; De Fonseka, Duneesha; Blyth, Kevin G; Smith, Nicola A; Piccolo, Francesco; Martin, Geoffrey; Wong, Donny; Edey, Anthony; Maskell, Nick; Lee, Y C Gary

    2017-06-01

    Intrapleural therapy with a combination of tissue plasminogen activator (tPA) 10 mg and DNase 5 mg administered twice daily has been shown in randomized and open-label studies to successfully manage over 90% of patients with pleural infection without surgery. Potential bleeding risks associated with intrapleural tPA and its costs remain important concerns. The aim of the ongoing Alteplase Dose Assessment for Pleural infection Therapy (ADAPT) project is to investigate the efficacy and safety of dose de-escalation for intrapleural tPA. The first of several planned studies is presented here. To evaluate the efficacy and safety of a reduced starting dose regimen of 5 mg of tPA with 5 mg of DNase administered intrapleurally for pleural infection. Consecutive patients with pleural infection at four participating centers in Australia, the United Kingdom, and New Zealand were included in this observational, open-label study. Treatment was initiated with tPA 5 mg and DNase 5 mg twice daily. Subsequent dose escalation was permitted at the discretion of the attending physician. Data relating to treatment success, radiological and systemic inflammatory changes (blood C-reactive protein), volume of fluid drained, length of hospital stay, and treatment complications were extracted retrospectively from the medical records. We evaluated 61 patients (41 males; age, 57 ± 16 yr). Most patients (n = 58 [93.4%]) were successfully treated without requiring surgery for pleural infection. Treatment success was corroborated by clearance of pleural opacities visualized by chest radiography (from 42% [interquartile range, 22-58] to 16% [8-31] of hemithorax; P < 0.001), increase in pleural fluid drainage (from 175 ml in the 24 h preceding treatment to 2,025 ml [interquartile range, 1,247-2,984] over 72 h of therapy; P <  0.05) and a reduction in blood C-reactive protein (P < 0.05). Seven patients (11.5%) had dose escalation of tPA to 10 mg. Three patients underwent

  4. Azithromycin to prevent bronchopulmonary dysplasia in ureaplasma-infected preterm infants: pharmacokinetics, safety, microbial response, and clinical outcomes with a 20-milligram-per-kilogram single intravenous dose.

    Science.gov (United States)

    Viscardi, Rose M; Othman, Ahmed A; Hassan, Hazem E; Eddington, Natalie D; Abebe, Elias; Terrin, Michael L; Kaufman, David A; Waites, Ken B

    2013-05-01

    Ureaplasma respiratory tract colonization is associated with bronchopulmonary dysplasia (BPD) in preterm infants. Previously, we demonstrated that a single intravenous (i.v.) dose of azithromycin (10 mg/kg of body weight) is safe but inadequate to eradicate Ureaplasma spp. in preterm infants. We performed a nonrandomized, single-arm open-label study of the pharmacokinetics (PK) and safety of intravenous 20-mg/kg single-dose azithromycin in 13 mechanically ventilated neonates with a gestational age between 24 weeks 0 days and 28 weeks 6 days. Pharmacokinetic data from 25 neonates (12 dosed with 10 mg/kg i.v. and 13 dosed with 20 mg/kg i.v.) were analyzed using a population modeling approach. Using a two-compartment model with allometric scaling of parameters on body weight (WT), the population PK parameter estimates were as follows: clearance, 0.21 liter/h × WT(kg)(0.75) [WT(kg)(0.75) indicates that clearance was allometrically scaled on body weight (in kilograms) with a fixed exponent of 0.75]; intercompartmental clearance, 2.1 liters/h × WT(kg)(0.75); central volume of distribution (V), 1.97 liters × WT (kg); and peripheral V, 17.9 liters × WT (kg). There was no evidence of departure from dose proportionality in azithromycin exposure over the tested dose range. The calculated area under the concentration-time curve over 24 h in the steady state divided by the MIC90 (AUC24/MIC90) for the single dose of azithromycin (20 mg/kg) was 7.5 h. Simulations suggest that 20 mg/kg for 3 days will maintain azithromycin concentrations of >MIC50 of 1 μg/ml for this group of Ureaplasma isolates for ≥ 96 h after the first dose. Azithromycin was well tolerated with no drug-related adverse events. One of seven (14%) Ureaplasma-positive subjects and three of six (50%) Ureaplasma-negative subjects developed physiologic BPD. Ureaplasma was eradicated in all treated Ureaplasma-positive subjects. Simulations suggest that a multiple-dose regimen may be efficacious for microbial

  5. Dextrose boluses versus burette dextrose infusions in prevention of hypoglycemia among preterms admitted at Mulago Hospital: an open label randomized clinical trial.

    Science.gov (United States)

    Kutamba, E; Lubega, S; Mugalu, J; Ouma, J; Mupere, E

    2014-09-01

    Hypoglycemia is a major cause of morbidity and mortality among preterm infants and its management remains a challenge in resource limited settings. Use of dextrose infusion by the recommended infusion pumps is not feasible in our environment due to their high costs and yet the current use of mini dextrose boluses with syringes as adapted at Mulago national referral and tertiary teaching hospital has unknown efficacy in prevention of hypoglycemia. We determined the efficacy of dextrose infusions by burettes versus two hourly dextrose boluses in prevention of hypoglycemia among preterms admitted in the first 72 hours at Special Care Unit, Mulago Hospital. One hundred and forty preterms aged 0 to 24 hours of life were randomized to receive 10% IV dextrose either as mini boluses or by infusion using burettes in an open label clinical trial. Blood glucose was measured at 0, two hourly for next 6 hours, 6 hourly for next 12 hours and thereafter 12 hourly until end of 72 hours following admission. Primary end point was incidence of hypoglycemia (random blood sugar (RBS) dextrose infusion was computed using 1-RR. From February 2012 to April 2012, 68 preterms in the bolus arm and 72 in the infusion arm were studied. Hypoglycemia was detected in 34% (48/140). The incidence of hypoglycemia in the bolus arm was 59% (40/68) compared to 11% (8/72) in the infusion arm (RR; 0.19, 95% CI; 0.09-0.37). Efficacy (1-RR) of infusion by burettes versus boluses in prevention of hypoglycemia among preterms was 0.81 (95% CI; 0.63-0.90). Continuous 10% dextrose infusion by burettes reduced the incidence of hypoglycemia by 81% in the first 72 hours of admission compared to two hourly 10% mini dextrose boluses among preterms admitted at Special Care Unit, Mulago Hospital. (ClinicalTrials.gov Identifier: NCT01688674).

  6. Sudarshan Kriya yoga improves quality of life in healthy people living with HIV (PLHIV: results from an open label randomized clinical trial

    Directory of Open Access Journals (Sweden)

    N Mawar

    2015-01-01

    Full Text Available Background & objectives: Improving quality of life (QOL of healthy people living with HIV (PLHIV is critical needing home-based, long-term strategy. Sudarshan Kriya yoga (SKY intervention is acknowledged for its positive impact on health. It is hypothesised that SKY would improve PLHIV′s QOL, justifying an evaluation. Methods: In this open label randomized controlled pilot trial, 61 adult PLHIV with CD4 count more than 400 cells/µl and Karnofsky scale score above 70 were enrolled. Those with cardiac disease, jaundice, tuberculosis, or on antiretroviral therapy/yoga intervention were excluded. All were given standard care, randomized to SKY intervention (31: I-SKY and only standard of care in control (30: O-SOC arms. The I-SKY participants were trained for six days to prepare for daily practice of SKY at home for 30 min. A validated 31-item WHOQOL-HIVBREF questionnaire was used to document effect in both arms from baseline to three visits at 4 wk interval. Results: Baseline QOL scores, hypertension and CD4 count were similar in both arms. An overall 6 per cent improvement of QOL scores was observed in I-SKY group as compared to O-SOC group, after controlling for baseline variables like age, gender, education and occupation ( p0 =0.016; 12 per cent for physical ( p0 =0.004, 11 per cent psychological ( p0 =0.023 and 9 per cent level of independence ( p0 =0.001 domains. Improvement in I-SKY observed at post-training and in the SKY adherence group showed increase in these two domains. Conclusions: A significant improvement in QOL scores was observed for the three health related QOL domains in SKY intervention arm. This low cost strategy improved physical and psychological state of PLHIV calling for upscaling with effective monitoring for sustainability of quality of life.

  7. Bone health nutraceuticals alter microarray mRNA gene expression: A randomized, parallel, open-label clinical study.

    Science.gov (United States)

    Lin, Yumei; Kazlova, Valentina; Ramakrishnan, Shyam; Murray, Mary A; Fast, David; Chandra, Amitabh; Gellenbeck, Kevin W

    2016-01-15

    Dietary intake of fruits and vegetables has been suggested to have a role in promoting bone health. More specifically, the polyphenols they contain have been linked to physiological effects related to bone mineral density and bone metabolism. In this research, we use standard microarray analyses of peripheral whole blood from post-menopausal women treated with two fixed combinations of plant extracts standardized to polyphenol content to identify differentially expressed genes relevant to bone health. In this 28-day open-label study, healthy post-menopausal women were randomized into three groups, each receiving one of three investigational fixed combinations of plant extracts: an anti-resorptive (AR) combination of pomegranate fruit (Punica granatum L.) and grape seed (Vitis vinifera L.) extracts; a bone formation (BF) combination of quercetin (Dimorphandra mollis Benth) and licorice (Glycyrrhiza glabra L.) extracts; and a fixed combination of all four plant extracts (AR plus BF). Standard microarray analysis was performed on peripheral whole blood samples taken before and after each treatment. Annotated genes were analyzed for their association to bone health by comparison to a gene library. The AR combination down-regulated a number of genes involved in reduction of bone resorption including cathepsin G (CTSG) and tachykinin receptor 1 (TACR1). The AR combination also up-regulated genes associated with formation of extracellular matrix including heparan sulfate proteoglycan 2 (HSPG2) and hyaluronoglucosaminidase 1 (HYAL1). In contrast, treatment with the BF combination resulted in up-regulation of bone morphogenetic protein 2 (BMP-2) and COL1A1 (collagen type I α1) genes which are linked to bone and collagen formation while down-regulating genes linked to osteoclastogenesis. Treatment with a combination of all four plant extracts had a distinctly different effect on gene expression than the results of the AR and BF combinations individually. These results could

  8. Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report.

    Science.gov (United States)

    Osório, Flávia de L; Sanches, Rafael F; Macedo, Ligia R; Santos, Rafael G dos; Maia-de-Oliveira, João P; Wichert-Ana, Lauro; Araujo, Draulio B de; Riba, Jordi; Crippa, José A; Hallak, Jaime E

    2015-01-01

    Ayahuasca (AYA), a natural psychedelic brew prepared from Amazonian plants and rich in dimethyltryptamine (DMT) and harmine, causes effects of subjective well-being and may therefore have antidepressant actions. This study sought to evaluate the effects of a single dose of AYA in six volunteers with a current depressive episode. Open-label trial conducted in an inpatient psychiatric unit. Statistically significant reductions of up to 82% in depressive scores were observed between baseline and 1, 7, and 21 days after AYA administration, as measured on the Hamilton Rating Scale for Depression (HAM-D), the Montgomery-Åsberg Depression Rating Scale (MADRS), and the Anxious-Depression subscale of the Brief Psychiatric Rating Scale (BPRS). AYA administration resulted in nonsignificant changes in Young Mania Rating Scale (YMRS) scores and in the thinking disorder subscale of the BPRS, suggesting that AYA does not induce episodes of mania and/or hypomania in patients with mood disorders and that modifications in thought content, which could indicate psychedelic effects, are not essential for mood improvement. These results suggest that AYA has fast-acting anxiolytic and antidepressant effects in patients with a depressive disorder.

  9. Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report

    Directory of Open Access Journals (Sweden)

    Flávia de L. Osório

    2015-03-01

    Full Text Available Objectives: Ayahuasca (AYA, a natural psychedelic brew prepared from Amazonian plants and rich in dimethyltryptamine (DMT and harmine, causes effects of subjective well-being and may therefore have antidepressant actions. This study sought to evaluate the effects of a single dose of AYA in six volunteers with a current depressive episode. Methods: Open-label trial conducted in an inpatient psychiatric unit. Results: Statistically significant reductions of up to 82% in depressive scores were observed between baseline and 1, 7, and 21 days after AYA administration, as measured on the Hamilton Rating Scale for Depression (HAM-D, the Montgomery-Åsberg Depression Rating Scale (MADRS, and the Anxious-Depression subscale of the Brief Psychiatric Rating Scale (BPRS. AYA administration resulted in nonsignificant changes in Young Mania Rating Scale (YMRS scores and in the thinking disorder subscale of the BPRS, suggesting that AYA does not induce episodes of mania and/or hypomania in patients with mood disorders and that modifications in thought content, which could indicate psychedelic effects, are not essential for mood improvement. Conclusions: These results suggest that AYA has fast-acting anxiolytic and antidepressant effects in patients with a depressive disorder.

  10. Does Increasing the Dose of Abobotulinumtoxina Impact the Duration of Effectiveness for the Treatment of Moderate to Severe Glabellar Lines?

    Science.gov (United States)

    Joseph, John H; Eaton, Laura L; Robinson, James; Pontius, Allison; Williams, Edwin F

    2016-12-01

    To evaluate the duration of effect of a single dose of 120 units of abobotulinumtoxinA for the treatment of moderate to severe glabellar lines. Investigator-initiated, prospective, multi-center, open-label study. This open-label trial of thirty subjects with moderate to severe glabellar lines at maximum frown was per- formed at 2 private plastic surgery clinics. 120 units of abobotulinumtoxinA was injected in 5 equal aliquots (24 units each) into each of 5 injection sites in the glabellar complex. Investigator and subject assessments of wrinkle severity at maximum frown and repose using 4-point scales and adverse events were conducted. Follow-up was monthly for up to 11 months. The median duration of response for all subjects, as assessed by the investigator, was 150 days (95% CI: 120, 180). The median duration of response was 165 days (95% CI: 90, 180) for subjects with Grade 2 (Moderate) wrinkles at baseline and 75 days (95% CI: 30, 120) for subjects with Grade 3 (Severe) wrinkles at baseline. Overall, 76.7% of subjects had a duration of ≥ 120 days. At the end of study (day 300) 9/16 (53%) of subjects who were Grade 3 at baseline still rated themselves as not returning to Grade 3, demonstrating ongoing improvement. Adverse events were mild and transient. There were no events of lid or brow ptosis. The 120 units of abobotulinumtoxinA were significantly effective in reducing glabellar lines in subjects with Grade 2 (Moderate) wrinkles at baseline for a longer duration than the reported 85 days in the FDA Phase III randomized, placebo-controlled clinical studies using a standard 50 unit dose. Subject satisfaction was high. There was no increase in the incidence of adverse events with this higher dose. J Drugs Dermatol. 2016;15(12):1544-1549.

  11. The effectiveness, reproducibility, and durability of tailored mobile coaching on diabetes management in policyholders: A randomized, controlled, open-label study.

    Science.gov (United States)

    Lee, Da Young; Park, Jeongwoon; Choi, Dooah; Ahn, Hong-Yup; Park, Sung-Woo; Park, Cheol-Young

    2018-02-26

    This randomized, controlled, open-label study conducted in Kangbuk Samsung Hospital evaluated the effectiveness, reproducibility, and durability of tailored mobile coaching (TMC) on diabetes management. The participants included 148 Korean adult policyholders with type 2 diabetes divided into the Intervention-Maintenance (I-M) group (n = 74) and Control-Intervention (C-I) group (n = 74). Intervention was the addition of TMC to typical diabetes care. In the 6-month phase 1, the I-M group received TMC, and the C-I group received their usual diabetes care. During the second 6-month phase 2, the C-I group received TMC, and the I-M group received only regular information messages. After the 6-month phase 1, a significant decrease (0.6%) in HbA1c levels compared with baseline values was observed in only the I-M group (from 8.1 ± 1.4% to 7.5 ± 1.1%, P < 0.001 based on a paired t-test). At the end of phase 2, HbA1c levels in the C-I group decreased by 0.6% compared with the value at 6 months (from 7.9 ± 1.5 to 7.3 ± 1.0, P < 0.001 based on a paired t-test). In the I-M group, no changes were observed. Both groups showed significant improvements in frequency of blood-glucose testing and exercise. In conclusion, addition of TMC to conventional treatment for diabetes improved glycemic control, and this effect was maintained without individualized message feedback.

  12. An open-label tolerability study of BL-1020 antipsychotic: a novel gamma aminobutyric acid ester of perphenazine.

    Science.gov (United States)

    Anand, Ravi; Geffen, Yona; Vasile, Daniel; Dan, Irina

    2010-01-01

    BL-1020, a novel gamma aminobutyric acid (GABA) ester of perphenazine, is a new oral antipsychotic with a strong affinity for dopamine and serotonin receptors. Unlike first- and second-generation antipsychotics, it has agonist activity at GABA(A). This is the first study to examine tolerability and safety of BL-1020 in schizophrenia. This was a phase-II, open-label, multicenter, 6-week study treating patients (n = 36) with chronic schizophrenia. Dosing started at 20 mg/d and increased over 7 days to 40 mg/d. Weekly assessments were conducted. All but 1 patient was titrated to 30 mg/d at day 4; on day 7, 30 were titrated to 40 mg/d. Four patients discontinued the study prematurely. There was no clinically relevant increase in vital signs, sedation, dizziness, or other central nervous system effects or electrocardiogram or laboratory abnormalities and a small increase in weight. Ten patients experienced extrapyramidal symptoms (EPS) requiring treatment with an anticholinergic; 4 patients were unable to reach maximum dose because of EPS. Extrapyramidal Symptom Rating Scale did not indicate clinically significant changes in EPS. The most common adverse event was insomnia (6 patients); other frequent adverse effects (all n = 3) were extrapyramidal disorder, headache, parkinsonism, tremor, and hyperprolactinemia. There was improvement on Positive and Negative Syndrome Scale and Clinical Global Impression of Change with 22 patients showing at least 20% decrease by end point on Positive and Negative Syndrome Scale and 31 patients showing at least minimal improvement on Clinical Global Impression of Change. These data suggest that 20 to 40 mg/d of BL-1020 is associated with clinically relevant improvement of psychosis with no worsening of EPS and support further testing in randomized controlled trials.

  13. Laparoscopic Versus Open Resection for Colorectal Liver Metastases: The OSLO-COMET Randomized Controlled Trial.

    Science.gov (United States)

    Fretland, Åsmund Avdem; Dagenborg, Vegar Johansen; Bjørnelv, Gudrun Maria Waaler; Kazaryan, Airazat M; Kristiansen, Ronny; Fagerland, Morten Wang; Hausken, John; Tønnessen, Tor Inge; Abildgaard, Andreas; Barkhatov, Leonid; Yaqub, Sheraz; Røsok, Bård I; Bjørnbeth, Bjørn Atle; Andersen, Marit Helen; Flatmark, Kjersti; Aas, Eline; Edwin, Bjørn

    2018-02-01

    To perform the first randomized controlled trial to compare laparoscopic and open liver resection. Laparoscopic liver resection is increasingly used for the surgical treatment of liver tumors. However, high-level evidence to conclude that laparoscopic liver resection is superior to open liver resection is lacking. Explanatory, assessor-blinded, single center, randomized superiority trial recruiting patients from Oslo University Hospital, Oslo, Norway from February 2012 to January 2016. A total of 280 patients with resectable liver metastases from colorectal cancer were randomly assigned to undergo laparoscopic (n = 133) or open (n = 147) parenchyma-sparing liver resection. The primary outcome was postoperative complications within 30 days (Accordion grade 2 or higher). Secondary outcomes included cost-effectiveness, postoperative hospital stay, blood loss, operation time, and resection margins. The postoperative complication rate was 19% in the laparoscopic-surgery group and 31% in the open-surgery group (12 percentage points difference [95% confidence interval 1.67-21.8; P = 0.021]). The postoperative hospital stay was shorter for laparoscopic surgery (53 vs 96 hours, P < 0.001), whereas there were no differences in blood loss, operation time, and resection margins. Mortality at 90 days did not differ significantly from the laparoscopic group (0 patients) to the open group (1 patient). In a 4-month perspective, the costs were equal, whereas patients in the laparoscopic-surgery group gained 0.011 quality-adjusted life years compared to patients in the open-surgery group (P = 0.001). In patients undergoing parenchyma-sparing liver resection for colorectal metastases, laparoscopic surgery was associated with significantly less postoperative complications compared to open surgery. Laparoscopic resection was cost-effective compared to open resection with a 67% probability. The rate of free resection margins was the same in both groups. Our results support the continued

  14. Effects of low calcium dialysate on the progression of coronary artery calcification in hemodialysis patients: An open-label 12-month randomized clinical trial.

    Science.gov (United States)

    Kim, Soo Jin; Lee, Young-Ki; Oh, Jieun; Cho, AJin; Noh, Jung Woo

    2017-09-15

    The association between the dialysate calcium level and coronary artery calcification (CAC) has not yet been evaluated in hemodialysis patients. The objective of this study was to determine whether lowering the dialysate calcium levels would decrease the progression of coronary artery calcification (CAC) compared to using standard calcium dialysate. We conducted an open-label randomized trial with parallel groups. The patients were randomly assigned to either 12-month treatment with low calcium dialysate (LCD; 1.25mmol/L, n=36) or standard calcium dialysate (SCD; 1.5mmol/L, n=40). The primary outcome was the change in the CAC scores assessed by 64-slice multidetector computed tomography after 12months. During the treatment period, CAC scores increased in both groups, especially significant in LCD group (402.5±776.8, 580.5±1011.9, P=0.004). When we defined progressors as patients at second and third tertiles of CAC changes, progressor group had a higher proportion of LCD-treated patients than SCD-treated patients (P=0.0229). In multivariate analysis, LCD treatment is a significant risk factor for increase in CAC scores (odds ratio=5.720, 95% CI: 1.219-26.843, P=0.027). Use of LCD may accelerate the progression of CAC in patients with chronic hemodialysis over a 12-month period. Clinical Research Information Service [Internet]; Osong (Chungcheongbuk-do): Korea Centers for Disease Control and Prevention, Ministry of Health and Welfare (Republic of Korea), 2010: KCT0000942. Available from: https://cris.nih.go.kr/cris/search/search_result_st01_kren.jsp?seq=3572&sLeft=2&type=my. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  15. Efficacy and safety of benzalkonium chloride-free fixed-dose combination of latanoprost and timolol in patients with open-angle glaucoma or ocular hypertension

    Directory of Open Access Journals (Sweden)

    Bhagat P

    2014-06-01

    Full Text Available Purvi Bhagat,1 Kalyani Sodimalla,2 Chandrima Paul,3 Surinder S Pandav,4 Ganesh V Raman,5 Rengappa Ramakrishnan,6 Abhijeet Joshi,7 Atul Raut7 1Glaucoma Clinic, M & J Western Regional Institute of Ophthalmology, Civil Hospital, Ahmedabad, Gujarat, India; 2Glaucoma Department, PBMA’s H.V. Desai Eye Hospital, Maharashtra, India; 3Glaucoma Service, B B Eye Foundation, Kolkata, India; 4Advanced Eye Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India; 5Glaucoma Clinic, Aravind Eye Hospital, Coimbatore, Tamilnadu, India; 6Glaucoma Clinic, Aravind Eye Hospital, Tirunelveli, Tamilnadu, India; 7Clinical Research Department, Sun Pharma Advanced Research Company Ltd, Mumbai, Maharashtra, India Background: Benzalkonium chloride (BAK is a common preservative in topical ocular preparations; however, prolonged use may lead to deleterious effects on the ocular surface, affecting quality of life and reducing adherence to treatment and overall outcomes. This study compared the intraocular pressure (IOP-lowering efficacy and safety of a novel once-daily, BAK-free, fixed-dose combination of latanoprost plus timolol with latanoprost or timolol administered as monotherapy or concomitantly. Methods: This was a 6-week, randomized, open-label, parallel-group, active-controlled study in patients aged ≥18 years with open-angle glaucoma or ocular hypertension. A total of 227 patients were randomized to either a once-daily, BAK-free, fixed-dose combination of latanoprost 0.005%/timolol 0.5% ophthalmic solution or concomitant administration of once-daily latanoprost 0.005% plus twice-daily timolol 0.5% or once-daily latanoprost 0.005% monotherapy, or twice-daily timolol 0.5% monotherapy. Efficacy end points were assessed at three time points on visits at weeks 1, 2, 4, and 6 versus baseline. Results: The IOP-lowering efficacy of the fixed-dose combination of latanoprost/timolol was similar to that of latanoprost plus timolol administered

  16. Evaluation of the effect of multiple doses of lansoprazole on the pharmacokinetics and safety of ponatinib in healthy subjects.

    Science.gov (United States)

    Narasimhan, Narayana I; Dorer, David J; Davis, Jeffrey; Turner, Christopher D; Sonnichsen, Daryl

    2014-10-01

    In vitro studies have demonstrated that the aqueous solubility of the tyrosine kinase inhibitor ponatinib decreases as pH increases. The primary aim of this study was to assess the effects of the gastric proton pump inhibitor lansoprazole on the pharmacokinetics of ponatinib. The single-dose safety profile of ponatinib with and without coadministration of lansoprazole was also characterized. This was a phase I, open-label, non-randomized, two-period crossover study in 20 healthy subjects aged 18-55 years. Subjects received a single oral dose of ponatinib 45 mg alone on day 1, an oral dose of lansoprazole 60 mg on day 14, and ponatinib 45 mg plus lansoprazole 60 mg on day 15. Lansoprazole coadministration resulted in a 1-h increase in the time to maximum plasma concentration (t max) of ponatinib (6 vs. 5 h post-dose; P lansoprazole versus ponatinib alone (40.67 vs. 53.96 ng/mL). Importantly, lansoprazole did not decrease the overall ponatinib systemic exposure as assessed by the ponatinib area under the plasma concentration-time curve from time zero to infinity (AUC∞ 1,153 ng·h/mL for lansoprazole + ponatinib vs. 1,222 ng·h/mL for ponatinib alone). The safety profile was considered acceptable when ponatinib was administered alone or with lansoprazole. Although coadministration of lansoprazole led to a modest, albeit statistically significant, reduction in ponatinib C max, overall systemic exposure to ponatinib did not change. The findings suggest that no dose adjustment is necessary when ponatinib is administered with drugs that increase gastric pH.

  17. Alternating Mupirocin/Gentamicin is Associated with Increased Risk of Fungal Peritonitis as Compared with Gentamicin Alone - Results of a Randomized Open-Label Controlled Trial.

    Science.gov (United States)

    Wong, Ping-Nam; Tong, Gensy M W; Wong, Yuk-Yi; Lo, Kin-Yee; Chan, Shuk-Fan; Lo, Man-Wai; Lo, Kwok-Chi; Ho, Lo-Yi; Tse, Cindy W S; Mak, Siu-Ka; Wong, Andrew K M

    2016-01-01

    ♦ Catheter-related infection, namely exit-site infection (ESI) and peritonitis, is a major infectious complication and remains a main cause of technique failure for patients receiving peritoneal dialysis (PD). Topical application of antibiotic cream might reduce catheter-related infection but emergence of resistant or opportunistic organisms could be a concern. Optimal topical agents and regimens remain to be determined. We did a study to examine the effect of an alternating topical antibiotic regimen in preventing catheter-related infection. ♦ We performed a single-center, randomized, open-label study to compare daily topical application of gentamicin cream with a gentamicin/mupirocin alternate regimen to the exit site. Patients randomized to alternating regimen were asked to have daily application of gentamicin cream in odd months and mupirocin cream in even months. Primary outcomes were ESI and peritonitis. Secondary outcomes were catheter removal or death caused by catheter-related infection. A total of 146 patients (71, gentamicin group; 75, alternating regimen group) were enrolled with a total follow-up duration of 174 and 181 patient-years for gentamicin and alternating groups, respectively. All patients were followed up until catheter removal, death, transfer to another unit, transplantation or the end of the study on March 31, 2014. There were no significant differences in the age, sex, dialysis vintage, and rate of diabetes, helper-assisted dialysis and methicillin-resistant Staphylococcus aureus (MRSA) carriage state. ♦ No difference was seen in the time to first ESI or peritonitis. However, the time to first gram-negative peritonitis seemed longer for the gentamicin group (p = 0.055). The 2 groups showed a similar rate of ESI (0.17/yr vs 0.19/yr, p = 0.93) but P. aeruginosa ESI was less common in the gentamicin group (0.06/yr vs 0.11/yr, p Peritonitis rate was significantly lower in the gentamicin group (0.22/yr vs 0.32/yr, p peritonitis (0.08/yr

  18. Efficacy and Safety of Azithromycin-Chloroquine versus Sulfadoxine-Pyrimethamine for Intermittent Preventive Treatment of Plasmodium falciparum Malaria Infection in Pregnant Women in Africa: An Open-Label, Randomized Trial.

    Directory of Open Access Journals (Sweden)

    Joshua Kimani

    Full Text Available The World Health Organization recommends intermittent preventive treatment in pregnancy (IPTp with sulfadoxine-pyrimethamine (SP in African regions with moderate to high malaria transmission. However, growing resistance to SP threatens the effectiveness of IPTp-SP, and alternative drugs are needed. This study tested the efficacy, tolerability, and safety of a fixed-dose combination azithromycin-chloroquine (AZCQ; 250 mg AZ/155 mg CQ base for IPTp relative to IPTp-SP.A randomized, Phase 3, open-label, multi-center study was conducted in sub-Saharan Africa (Benin, Kenya, Malawi, Tanzania, and Uganda between October 2010 and November 2013. Pregnant women received 3 IPTp courses with AZCQ (each course: 1,000/620 mg AZCQ QD for 3 days or SP (each course 1,500/75 mg SP QD for 1 day at 4- to 8-week intervals during the second and third trimester. Long-lasting insecticide-treated bednets were also provided at enrollment. Study participants were followed up until day 28 post delivery (time window: day 28-42. The primary endpoint was the proportion of participants with sub-optimal pregnancy outcomes (a composite endpoint comprising live-borne neonates with low birth weight [LBW, 28 weeks], abortion [≤28 weeks], lost to follow-up prior to observation of pregnancy outcome, or missing birth weight. The study was terminated early after recruitment of 2,891 of the planned 5,044 participants, due to futility observed in a pre-specified 35% interim analysis. In the final intent-to-treat dataset, 378/1,445 (26.2% participants in the AZCQ and 342/1,445 (23.7% in the SP group had sub-optimal pregnancy outcomes, with an estimated risk ratio (RR of 1.11 (95% CI: 0.97, 1.25; p = 0.12. There was no significant difference in the incidence of LBW between treatment groups (57/1138 [5.0%] in the AZCQ group, 68/1188 [5.7%] in the SP group, RR 0.87 [95% CI: 0.62, 1.23]; p = 0.44. IPTp-AZCQ was less well-tolerated in mothers than IPTp-SP. Occurrences of congenital anomalies

  19. Bioequivalence of a fixed-dose repaglinide/metformin combination tablet and equivalent doses of repaglinide and metformin tablets
.

    Science.gov (United States)

    Cho, Hea-Young; Ngo, Lien; Kim, Sang-Ki; Choi, Yoonho; Lee, Yong-Bok

    2018-06-01

    This study was conducted to determine whether a fixed-dose combination (FDC) tablet of repaglinide/metformin (2/500 mg) is equivalent to coadministration of equivalent doses of individual (EDI) tablets of repaglinide (2 mg) and metformin (500 mg) in healthy Korean male subjects. This study was conducted as an open-label, randomized, single-dose, two-period, two-sequence crossover design in 50 healthy Korean male subjects who received an FDC tablet or EDI tablets. Plasma concentrations of repaglinide and metformin were determined for up to 24 hours using a validated UPLC-MS/MS method. Bioequivalence was assessed according to current guidelines issued by the U.S. Food and Drug Administration (FDA) and Korean legislation. Tolerability was also evaluated throughout the study via subject interview, vital signs, and blood sampling. Point estimates (90% CIs) for AUC0-t, AUC0-∞, and Cmax based on EDI tablets were 110.07 (102.25 - 118.49), 109.90 (101.70 - 118.39), and 112.60 (101.49 - 124.85), respectively, for repaglinide. They were 95.18 (89.62 - 101.05), 95.00 (89.74 - 100.65), and 98.44 (92.72 - 104.50), respectively, for metformin. These results satisfied the bioequivalence criteria of 80.00 - 125.00% proposed by the FDA and Korean legislation. Results of pharmacokinetic analysis suggested that repaglinide and metformin in FDC tablets were bioequivalent to EDI tablets of repaglinide (2 mg) and metformin (500 mg) in healthy Korean male subjects. Both formulations appeared to be well tolerated.
.

  20. Gatifloxacin versus chloramphenicol for uncomplicated enteric fever: an open-label, randomised, controlled trial.

    Science.gov (United States)

    Arjyal, Amit; Basnyat, Buddha; Koirala, Samir; Karkey, Abhilasha; Dongol, Sabina; Agrawaal, Krishna Kumar; Shakya, Nikki; Shrestha, Kabina; Sharma, Manish; Lama, Sanju; Shrestha, Kasturi; Khatri, Nely Shrestha; Shrestha, Umesh; Campbell, James I; Baker, Stephen; Farrar, Jeremy; Wolbers, Marcel; Dolecek, Christiane

    2011-06-01

    We aimed to investigate whether gatifloxacin, a new generation and affordable fluoroquinolone, is better than chloramphenicol for the treatment of uncomplicated enteric fever in children and adults. We did an open-label randomised superiority trial at Patan Hospital, Kathmandu, Nepal, to investigate whether gatifloxacin is more effective than chloramphenicol for treating uncomplicated enteric fever. Children and adults clinically diagnosed with enteric fever received either gatifloxacin (10 mg/kg) once a day for 7 days, or chloramphenicol (75 mg/kg per day) in four divided doses for 14 days. Patients were randomly allocated treatment (1:1) in blocks of 50, without stratification. Allocations were placed in sealed envelopes opened by the study physician once a patient was enrolled into the trial. Masking was not possible because of the different formulations and ways of giving the two drugs. The primary outcome measure was treatment failure, which consisted of at least one of the following: persistent fever at day 10, need for rescue treatment, microbiological failure, relapse until day 31, and enteric-fever-related complications. The primary outcome was assessed in all patients randomly allocated treatment and reported separately for culture-positive patients and for all patients. Secondary outcome measures were fever clearance time, late relapse, and faecal carriage. The trial is registered on controlled-trials.com, number ISRCTN 53258327. 844 patients with a median age of 16 (IQR 9-22) years were enrolled in the trial and randomly allocated a treatment. 352 patients had blood-culture-confirmed enteric fever: 175 were treated with chloramphenicol and 177 with gatifloxacin. 14 patients had treatment failure in the chloramphenicol group, compared with 12 in the gatifloxacin group (hazard ratio [HR] of time to failure 0·86, 95% CI 0·40-1·86, p=0·70). The median time to fever clearance was 3·95 days (95% CI 3·68-4·68) in the chloramphenicol group and 3·90 days

  1. Flash Glucose-Sensing Technology as a Replacement for Blood Glucose Monitoring for the Management of Insulin-Treated Type 2 Diabetes: a Multicenter, Open-Label Randomized Controlled Trial.

    Science.gov (United States)

    Haak, Thomas; Hanaire, Hélène; Ajjan, Ramzi; Hermanns, Norbert; Riveline, Jean-Pierre; Rayman, Gerry

    2017-02-01

    Glycemic control in participants with insulin-treated diabetes remains challenging. We assessed safety and efficacy of new flash glucose-sensing technology to replace self-monitoring of blood glucose (SMBG). This open-label randomized controlled study (ClinicalTrials.gov, NCT02082184) enrolled adults with type 2 diabetes on intensive insulin therapy from 26 European diabetes centers. Following 2 weeks of blinded sensor wear, 2:1 (intervention/control) randomization (centrally, using biased-coin minimization dependant on study center and insulin administration) was to control (SMBG) or intervention (glucose-sensing technology). Participants and investigators were not masked to group allocation. Primary outcome was difference in HbA1c at 6 months in the full analysis set. Prespecified secondary outcomes included time in hypoglycemia, effect of age, and patient satisfaction. Participants (n = 224) were randomized (149 intervention, 75 controls). At 6 months, there was no difference in the change in HbA1c between intervention and controls: -3.1 ± 0.75 mmol/mol, [-0.29 ± 0.07% (mean ± SE)] and -3.4 ± 1.04 mmol/mol (-0.31 ± 0.09%) respectively; p = 0.8222. A difference was detected in participants aged glucose-sensing technology use in type 2 diabetes with intensive insulin therapy results in no difference in HbA1c change and reduced hypoglycemia, thus offering a safe, effective replacement for SMBG. ClinicalTrials.gov identifier: NCT02082184. Abbott Diabetes Care.

  2. Dose-dependent pharmacokinetics of delavirdine in combination with amprenavir in healthy volunteers

    DEFF Research Database (Denmark)

    Justesen, Ulrik S; Klitgaard, Niels A; Brosen, Kim

    2004-01-01

    OBJECTIVES: To investigate different dose combinations of amprenavir and delavirdine in order to assess an optimal dose suitable for clinical use. METHODS: This was a prospective, open-label, controlled, three-period, multiple-dose study with nine healthy volunteers. The volunteers received three...

  3. Efficacy and safety of a flexible extended regimen of ethinylestradiol/drospirenone for the treatment of dysmenorrhea: a multicenter, randomized, open-label, active-controlled study

    Directory of Open Access Journals (Sweden)

    Momoeda M

    2017-05-01

    Full Text Available Mikio Momoeda,1 Masami Kondo,2 Joerg Elliesen,3 Masanobu Yasuda,2 Shigetomo Yamamoto,4 Tasuku Harada5 1Department of Integrated Women’s Health, St Luke’s International Hospital, Tokyo, 2Product Development, Bayer Yakuhin Ltd, Osaka, Japan; 3Global Clinical Development, Bayer AG, Berlin, Germany; 4Medical Affairs, Bayer Yakuhin Ltd, Osaka, 5Department of Obstetrics and Gynecology, Tottori University Faculty of Medicine, Tottori, Japan Background: Dysmenorrhea is a common condition in women, which is characterized by menstrual pain. Low-dose estrogen/progestin combined oral contraceptives have been shown to reduce the severity of dysmenorrhea symptoms, and a 28-day cyclic regimen of ethinylestradiol/drospirenone (28d regimen is approved for this indication in Japan. Aim: The aim of this study was to assess the safety and efficacy of a flexible extended regimen of ethinylestradiol/drospirenone (flexible regimen in Japanese women with dysmenorrhea. Methods: This multicenter, open-label study was performed in Japanese women with dysmenorrhea who, after a baseline observational phase, were randomized to receive ethinylestradiol 20 µg/drospirenone 3 mg in a flexible regimen (one tablet each day for 24–120 days followed by a 4-day tablet-free interval or in the standard 28d regimen (one tablet each day for 24 days, followed by 4 days of placebo tablets for six cycles. The primary endpoint was the number of days with dysmenorrhea of at least mild intensity over a 140-day evaluation period. Dysmenorrhea scores, bleeding patterns, and other pain-related parameters were also assessed. Results: A total of 216 women (mean age 29.7 years were randomized to the flexible regimen (n=108 or 28d regimen (n=108 and 212 were included in the full analysis sets (flexible regimen, n=105; 28d regimen, n=107. Women in the flexible-regimen group reported a mean of 3.4 fewer days with dysmenorrheic pain than women in the 28d-regimen group, with similar decreases in

  4. Intra-ocular pressure-lowering effects of a Rho kinase inhibitor, ripasudil (K-115), over 24 hours in primary open-angle glaucoma and ocular hypertension: a randomized, open-label, crossover study.

    Science.gov (United States)

    Tanihara, Hidenobu; Inoue, Toshihiro; Yamamoto, Tetsuya; Kuwayama, Yasuaki; Abe, Haruki; Suganami, Hideki; Araie, Makoto

    2015-06-01

    To investigate the intra-ocular pressure (IOP)-lowering effects of a selective Rho kinase inhibitor, ripasudil (K-115), over 24 hr in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT). In this multicenter, prospective, randomized, open-label, 3-period, Latin-square crossover clinical study, 28 patients with POAG or OHT whose IOP level was 21 mmHg or higher were subdivided into three groups. Each patient was treated with placebo and ripasudil in concentrations of 0.2 and 0.4%, at 9:00 and 21:00 on day 1 through a total of 3 periods separated by washout periods. IOP was measured at 9:00, 10:00, 11:00, 13:00, 16:00, 19:00, 21:00, 22:00 and 23:00 on day 1, and 1:00, 4:00, 7:00 and 9:00 on day 2 in sitting position using Goldmann applanation tonometer. Main outcome measure was the IOP reduction of placebo and ripasudil from baseline. The mean IOP reduction was -5.2 mmHg for 0.2%, -6.4 mmHg for 0.4% and -2.0 mmHg for placebo at 2 hr after the first instillation. Also, the corresponding values were -6.8 mmHg for 0.2%, -7.3 mmHg for 0.4% and -4.1 mmHg for placebo at 2 hr after the second instillation. Statistically significant IOP reduction, compared with placebo, was found for both 0.2 and 0.4% from 1 through 7 hr after each instillation. In safety, conjunctival hyperaemia was observed in 22 patients (79%) for 0.2%, 27 patients (96%) for 0.4% and three patients (11%) for placebo. Ripasudil is a promising new topical medication to lower IOP for at least 7 hr after instillations in patients with POAG or OHT. © 2014 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  5. A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles.

    Science.gov (United States)

    Kurosawa, Yuko; Nirengi, Shinsuke; Homma, Toshiyuki; Esaki, Kazuki; Ohta, Mitsuhiro; Clark, Joseph F; Hamaoka, Takafumi

    2015-06-25

    Our aim was to determine the quantitative effects of a single-dose of Nattokinase (NK) administration on coagulation/fibrinolysis parameters comprehensively in healthy male subjects. A double-blind, placebo-controlled cross-over NK intervention study was carried out in 12 healthy young males. Following the baseline blood draw, each subject was randomized to receive either a single-dose of 2,000 FU NK (NSK-SD, Japan Bio Science Laboratory Co., Ltd) or placebo with subsequent cross-over of the groups. Subjects donated blood samples at 2, 4, 6 and 8 hours following administration for analysis of coagulation/fibrinolysis parameters. As a result, D-dimer concentrations at 6, and 8 hours, and blood fibrin/fibrinogen degradation products at 4 hours after NK administration elevated significantly (p < 0.05, respectively). Factor VIII activity declined at 4 and 6 hours (p < 0.05, respectively), blood antithrombin concentration was higher at 2 and 4 hours (p < 0.05, respectively), and the activated partial thromboplastin time prolonged significantly at 2 and 4 hours following NK administration (p < 0.05 and p < 0.01, respectively). All the changes, however, were within the normal range. In conclusion, thus, a single-dose of NK administration appears enhancing fibrinolysis and anti-coagulation via several different pathways simultaneously.

  6. Photoinduced electron transfer in singly labeled thiouredopyrenetrisulfonate azurin derivatives

    DEFF Research Database (Denmark)

    Borovok, N; Kotlyar, A B; Pecht, I

    1999-01-01

    efficiency. TUPS derivatives of azurin, singly labeled at specific lysine residues, were prepared and purified to homogeneity by ion exchange HPLC. Transient absorption spectroscopy was used to directly monitor the rates of the electron transfer reaction from the photoexcited triplet state of TUPS to Cu......A novel method for the initiation of intramolecular electron transfer reactions in azurin is reported. The method is based on laser photoexcitation of covalently attached thiouredopyrenetrisulfonate (TUPS), the reaction that generates the low potential triplet state of the dye with high quantum......(II) and the back reaction from Cu(I) to the oxidized dye. For all singly labeled derivatives, the rate constants of copper ion reduction were one or two orders of magnitude larger than for its reoxidation, consistent with the larger thermodynamic driving force for the former process. Using 3-D coordinates...

  7. Metformin Treatment in Type 2 Diabetes in Pregnancy: An Active Controlled, Parallel-Group, Randomized, Open Label Study in Patients with Type 2 Diabetes in Pregnancy

    Directory of Open Access Journals (Sweden)

    Jahan Ara Ainuddin

    2015-01-01

    Full Text Available Aims. To assess the effect of metformin and to compare it with insulin treatment in patients with type 2 diabetes in pregnancy in terms of perinatal outcome, maternal complications, additional insulin requirement, and treatment acceptability. Methods. In this randomized, open label study, 206 patients with type 2 diabetes in pregnancy who met the eligibility criteria were selected from the antenatal clinics. Insulin was added to metformin treatment when required, to maintain the target glycemic control. The patients were followed up till delivery. Maternal, and perinatal outcomes and pharmacotherapeutic characteristics were recorded on a proforma. Results. Maternal characteristics were comparable in metformin and insulin treated group. 84.9% patients in metformin group required add-on insulin therapy at mean gestational age of 26.58 ± 3.85 weeks. Less maternal weight gain (P24 hours in metformin group (P<0.01. Significant reduction in cost of treatment was found in metformin group. Conclusion. Metformin alone or with add-on insulin is an effective and cheap treatment option for patients with type 2 diabetes in pregnancy. This trial is registered with clinical trial registration number: Clinical trials.gov NCT01855763.

  8. Metformin treatment in type 2 diabetes in pregnancy: an active controlled, parallel-group, randomized, open label study in patients with type 2 diabetes in pregnancy.

    Science.gov (United States)

    Ainuddin, Jahan Ara; Karim, Nasim; Zaheer, Sidra; Ali, Syed Sanwer; Hasan, Anjum Ara

    2015-01-01

    To assess the effect of metformin and to compare it with insulin treatment in patients with type 2 diabetes in pregnancy in terms of perinatal outcome, maternal complications, additional insulin requirement, and treatment acceptability. In this randomized, open label study, 206 patients with type 2 diabetes in pregnancy who met the eligibility criteria were selected from the antenatal clinics. Insulin was added to metformin treatment when required, to maintain the target glycemic control. The patients were followed up till delivery. Maternal, and perinatal outcomes and pharmacotherapeutic characteristics were recorded on a proforma. Maternal characteristics were comparable in metformin and insulin treated group. 84.9% patients in metformin group required add-on insulin therapy at mean gestational age of 26.58 ± 3.85 weeks. Less maternal weight gain (P pregnancy induced hypertension (P = 0.029) were observed in metformin treated group. Small for date babies were more in metformin group (P 24 hours in metformin group (P metformin group. Metformin alone or with add-on insulin is an effective and cheap treatment option for patients with type 2 diabetes in pregnancy. This trial is registered with clinical trial registration number: Clinical trials.gov NCT01855763.

  9. Safety, tolerability, and pharmacokinetics of single oral doses of tofacitinib, a Janus kinase inhibitor, in healthy volunteers.

    Science.gov (United States)

    Krishnaswami, Sriram; Boy, Mary; Chow, Vincent; Chan, Gary

    2015-03-01

    Tofacitinib is an oral Janus kinase inhibitor. This randomized, double-blind, parallel-group, placebo-controlled study was the first evaluation of tofacitinib in humans. The objectives were to characterize the safety and tolerability, pharmacokinetics (PK), and pharmacodynamics of escalating single tofacitinib doses in healthy subjects. Tofacitinib (0.1, 0.3, 1, 3, 10, 30, 60, and 100 mg) or placebo was administered as oral powder for constitution. For each dose, 7-9 subjects were randomized to tofacitinib and 3-5 subjects to placebo. Ninety-five males and females (age range 19-45) completed the study. Forty-nine treatment-emergent all-causality adverse events (AEs) were observed; nausea and headache were the most frequently reported. Tofacitinib PK was characterized by rapid absorption (time to peak serum concentration [Tmax ] 0.5-1 hour), rapid elimination (mean terminal half-lives 2.3-3.1 hours), and dose-proportional systemic exposures (peak serum concentration [Cmax ] and area under the serum concentration-time curve from time zero to infinity [AUC0-∞ ]). No appreciable correlation was observed between tofacitinib dose and lymphocyte subset counts. Single-dose tofacitinib up to 100 mg in healthy subjects had a safety profile of mostly mild AEs, and no deaths, serious AEs, severe AEs or discontinuations due to AEs. © 2014, The American College of Clinical Pharmacology.

  10. Single versus double dose praziquantel comparison on efficacy and Schistosoma mansoni re-infection in preschool-age children in Uganda

    DEFF Research Database (Denmark)

    Nalugwa, Allen; Nuwaha, Fred; Tukahebwa, Edridah Muheki

    2015-01-01

    BACKGROUND: Schistosoma mansoni infection is proven to be a major health problem of preschool-age children in sub-Saharan Africa, yet this age category is not part of the schistosomiasis control program. The objective of this study was to compare the impact of single and double dose praziquantel...... (PZQ) treatment on cure rates (CRs), egg reduction rates (ERRs) and re-infection rates 8 months later, in children aged 1-5 years living along Lake Victoria, Uganda. METHODOLOGY/PRINCIPAL FINDINGS: Infected children (n= 1017) were randomized to receive either a single or double dose of PZQ. Initially...... all children were treated with a single standard oral dose 40 mg/kg body weight of PZQ. Two weeks later a second dose was administered to children in the double dose treatment arm. Side effects were monitored at 30 minutes to 24 hours after each treatment. Efficacy in terms of CRs and ERRs for the two...

  11. Effect of heart failure reversal treatment as add-on therapy in patients with chronic heart failure: A randomized, open-label study.

    Science.gov (United States)

    Sane, Rohit; Aklujkar, Abhijeet; Patil, Atul; Mandole, Rahul

    The present study was designed to evaluate effect of heart failure reversal therapy (HFRT) using herbal procedure (panchakarma) and allied therapies, as add-on to standard CHF treatment (SCT) in chronic heart failure (CHF) patients. This open-label, randomized study conducted in CHF patients (aged: 25-65 years, ejection fraction: 30-65%), had 3-phases: 1-week screening, 6-week treatment (randomized [1:1] to HFRT+SCT or SCT-alone) and follow-up (12-week). Twice weekly HFRT (60-75min) consisting of snehana (external oleation), swedana (passive heat therapy), hrudaydhara (concoction dripping treatment) and basti (enema) was administered. Primary endpoints included evaluation of change in metabolic equivalents of task (MET) and peak oxygen uptake (VO 2peak ) from baseline, at end of 6-week treatment and follow-up at week-18 (non-parametric rank ANCOVA analysis). Safety and quality of life (QoL) was assessed. Seventy CHF patients (n=35, each treatment-arm; mean [SD] age: 53.0 [8.6], 80% men) were enrolled in the study. All patients completed treatment phase. Add-on HFRT caused a significant increase in METs (least square mean difference [LSMD], 6-week: 1.536, p=0.0002; 18-week: -1.254, p=0.0089) and VO 2peak (LSMD, 6-week: -5.52, p=0.0002; 18-week: -4.517, p=0.0089) as compared with SCT-alone. Results were suggestive of improved functional capacity in patients with HFRT (QoL; Mean [SD] HFRT+SCT vs. SCT-alone; 6-week: -0.44 [0.34] vs. -0.06 [0.25], p<0.0001 and 18-week: -0.53 [0.35] vs. -0.29 [0.26], p=0.0013). Seven treatment-emergent adverse events (mild severity) were reported in HFRT-arm. Findings of this study highlight therapeutic efficacy of add-on HFRT vs. SCT-alone in CHF patients. The non-invasive HFRT showed no safety concerns. Copyright © 2016. Published by Elsevier B.V.

  12. Effects of quetiapine and olanzapine in patients with psychosis and violent behavior: a pilot randomized, open-label, comparative study

    Directory of Open Access Journals (Sweden)

    Gobbi G

    2014-05-01

    Full Text Available Gabriella Gobbi,1,2 Stefano Comai,1 Guy Debonnel1,2,† 1Neurobiological Psychiatric Unit, Department of Psychiatry, McGill University and McGill University Health Center, 2Institut Philippe Pinel, Department of Psychiatry, Université de Montréal, Montréal, QC, Canada †Guy Debonnel passed away on November 4, 2006 Objective: Patients suffering from psychosis are more likely than the general population to commit aggressive acts, but the therapeutics of aggressive behavior are still a matter of debate. Methods: This pilot randomized, open-label study compared the efficacy of quetiapine versus olanzapine in reducing impulsive and aggressive behaviors (primary endpoints and psychotic symptoms (secondary endpoints from baseline to days 1, 7, 14, 28, 42, 56, and 70, in 15 violent schizophrenic patients hospitalized in a maximum-security psychiatric hospital. Results: Quetiapine (525±45 mg and olanzapine (18.5±4.8 mg were both efficacious in reducing Impulsivity Rating Scale from baseline to day 70. In addition, both treatments reduced the Brief Psychiatric Rating Scale, Positive and Negative Syndrome Scale, and Clinical Global Impression Scale scores at day 70 compared to baseline, and no differences were observed between treatments. Moreover, quetiapine, but not olanzapine, yielded an improvement of depressive symptoms in the items “depression” in Brief Psychiatric Rating Scale and “blunted affect” in Positive and Negative Syndrome Scale. Modified Overt Aggression Scale scores were also decreased from baseline to the endpoint, but due to the limited number of patients, it was not possible to detect a significant difference. Conclusion: In this pilot study, quetiapine and olanzapine equally decreased impulsive and psychotic symptoms after 8 weeks of treatment. Double-blind, large studies are needed to confirm the validity of these two treatments in highly aggressive and violent schizophrenic patients. Keywords: schizophrenia, aggression

  13. Open-label, dose escalation phase I study in healthy volunteers to evaluate the safety and pharmacokinetics of a human monoclonal antibody to Clostridium difficile toxin A.

    Science.gov (United States)

    Taylor, Claribel P; Tummala, Sanjeev; Molrine, Deborah; Davidson, Lisa; Farrell, Richard J; Lembo, Anthony; Hibberd, Patricia L; Lowy, Israel; Kelly, Ciaran P

    2008-06-25

    Recent data suggest that Clostridium difficile-associated diarrhea is becoming more severe and difficult to treat. Antibody responses to C. difficile toxin A are protective against symptomatic disease and recurrence. We examined the safety and pharmacokinetics (pk) of a novel neutralizing human monoclonal antibody against C. difficile toxin A (CDA1) in healthy adults. Five cohorts with 6 subjects each received a single intravenous infusion of CDA1 at escalating doses of 0.3, 1, 5, 10, and 20 mg/kg. Safety evaluations took place on days 1, 2, 3, 7, 14, 28, and 56 post-infusion. Samples for pk analysis were obtained before and after infusion, and at each safety evaluation. Serum CDA1 antibody concentrations and human anti-human antibody (HAHA) titers were measured with enzyme-linked immunosorbent assays. A noncompartmental model was used for pk analysis. Thirty subjects were enrolled. The median age was 27.5 yrs. There were no serious adverse events (AE) related to CDA1. Twenty-one of the 48 reported non-serious adverse events were possibly related to CDA1, and included transient blood pressure changes requiring no treatment, nasal congestion, headache, abdominal cramps, nausea, and self-limited diarrhea. Serum CDA1 concentrations increased with escalating doses: mean C(max) ranged from 6.82 microg/ml for the 0.3 mg/kg cohort to 511 microg/ml for the 20 mg/kg cohort. The geometric mean values of the half-life of CDA1 ranged between 25.3 and 31.8 days, and the volume of distribution approximated serum. No subject formed detectable HAHA titers. Administration of CDA1 as a single intravenous infusion was safe and well tolerated. C(max) increased proportionally with increasing doses. A randomized study of CDA1 in patients with C. difficile associated diarrhea is underway.

  14. 3D SEMANTIC LABELING OF ALS DATA BASED ON DOMAIN ADAPTION BY TRANSFERRING AND FUSING RANDOM FOREST MODELS

    Directory of Open Access Journals (Sweden)

    J. Wu

    2018-04-01

    Full Text Available Labeling 3D point cloud data with traditional supervised learning methods requires considerable labelled samples, the collection of which is cost and time expensive. This work focuses on adopting domain adaption concept to transfer existing trained random forest classifiers (based on source domain to new data scenes (target domain, which aims at reducing the dependence of accurate 3D semantic labeling in point clouds on training samples from the new data scene. Firstly, two random forest classifiers were firstly trained with existing samples previously collected for other data. They were different from each other by using two different decision tree construction algorithms: C4.5 with information gain ratio and CART with Gini index. Secondly, four random forest classifiers adapted to the target domain are derived through transferring each tree in the source random forest models with two types of operations: structure expansion and reduction-SER and structure transfer-STRUT. Finally, points in target domain are labelled by fusing the four newly derived random forest classifiers using weights of evidence based fusion model. To validate our method, experimental analysis was conducted using 3 datasets: one is used as the source domain data (Vaihingen data for 3D Semantic Labelling; another two are used as the target domain data from two cities in China (Jinmen city and Dunhuang city. Overall accuracies of 85.5 % and 83.3 % for 3D labelling were achieved for Jinmen city and Dunhuang city data respectively, with only 1/3 newly labelled samples compared to the cases without domain adaption.

  15. Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with cisplatin therapy: randomized, double-blind study protocol--EASE

    DEFF Research Database (Denmark)

    Grunberg, Steven; Chua, Daniel; Maru, Anish

    2011-01-01

    multiple-day NK1RA administration. Preliminary data suggested that single-dose aprepitant before chemotherapy could provide CINV protection throughout the overall risk phase (OP; 0 to 120 hours). This study compared a 3-day oral aprepitant schedule to a regimen containing a single dose of the intravenous...

  16. Efficacy and speed of onset of pain relief of fast-dissolving paracetamol on postsurgical dental pain: two randomized, single-dose, double-blind, placebo-controlled clinical studies.

    Science.gov (United States)

    Yue, Yong; Collaku, Agron; Brown, Jean; Buchanan, William L; Reed, Kenneth; Cooper, Stephen A; Otto, James

    2013-09-01

    Paracetamol (APAP), also known as acetaminophen, is the most commonly used over-the-counter analgesic for the treatment of mild-to-moderate pain. However, the speed of onset of pain relief is limited mainly to the standard, immediate-release formulation. Efficacy and speed of onset of pain relief are critical in acute pain situations such as postsurgical dental pain, because reducing pain can improve clinical outcome and reduce the risk of transition from acute pain to more chronic pain. Efficacy and rapid onset also reduce the risk of excessive dosing with the analgesic. We sought to investigate the dose-response efficacy and speed of onset of pain relief of a fast-dissolving APAP formulation compared with lower doses of APAP and placebo in dental patients after impacted third molar extraction. Two single-center, single-dose, randomized, placebo-controlled, double-blind, double-dummy, parallel-group studies (Study I and Study II) were conducted to evaluate the efficacy and speed of onset of pain relief of different doses of a fast-dissolving APAP tablet (FD-APAP), standard APAP, and placebo in patients with postsurgical dental pain following third molar extraction. In Study I, a single dose of FD-APAP 1000 mg, FD-APAP 500 mg, or placebo was given to 300 patients; in Study II, a single dose of FD-APAP 1000 mg, standard APAP 650 mg, or placebo was given to 401 patients. All 701 patients from both studies were included in the analysis and safety assessment. FD-APAP 1000 mg demonstrated significantly greater effect compared with FD-APAP 500 mg, APAP 650 mg, and placebo for all efficacy measurements, including sum of pain relief and pain intensity difference, total pain relief, sum of pain intensity difference, pain intensity difference, and pain relief score during 6 hours after the dose. Onset of confirmed first perceptible relief in subjects treated with FD-APAP 1000 mg was 15 minutes, which was 32% and 25% significantly shorter than onset of pain relief of FD

  17. 300,000 IU or 600,000 IU of oral vitamin D3 for treatment of nutritional rickets: a randomized controlled trial.

    Science.gov (United States)

    Mittal, Hema; Rai, Sunita; Shah, Dheeraj; Madhu, S V; Mehrotra, Gopesh; Malhotra, Rajeev Kumar; Gupta, Piyush

    2014-04-01

    To evaluate the non-inferiority of a lower therapeutic dose (300,000 IU) in comparison to standard dose (600,000) IU of Vitamin D for increasing serum 25(OH) D levels and achieving radiological recovery in nutritional rickets. Randomized, open-labeled, controlled trial. Tertiary care hospital. 76 children (median age 12 mo) with clinical and radiologically confirmed rickets. Oral vitamin D3 as 300,000 IU (Group 1; n=38) or 600,000 IU (Group 2; n=38) in a single day. Primary: Serum 25(OH)D, 12 weeks after administration of vitamin D3; Secondary: Radiological healing and serum parathormone at 12 weeks; and clinical and biochemical adverse effects. Serum 25(OH)D levels [geometric mean (95% CI)] increased significantly from baseline to 12 weeks after therapy in both the groups [Group 1: 7.58 (5.50–10.44) to 16.06 (12.71– 20.29) ng/mL, Prickets in under-five children although there is an unacceptably high risk of hypercalcemia in both groups. None of the regime is effective in normalization of vitamin D status in majority of patients, 3 months after administering the therapeutic dose.

  18. Single-Labeled Oligonucleotides Showing Fluorescence Changes upon Hybridization with Target Nucleic Acids

    Directory of Open Access Journals (Sweden)

    Gil Tae Hwang

    2018-01-01

    Full Text Available Sequence-specific detection of nucleic acids has been intensively studied in the field of molecular diagnostics. In particular, the detection and analysis of single-nucleotide polymorphisms (SNPs is crucial for the identification of disease-causing genes and diagnosis of diseases. Sequence-specific hybridization probes, such as molecular beacons bearing the fluorophore and quencher at both ends of the stem, have been developed to enable DNA mutation detection. Interestingly, DNA mutations can be detected using fluorescently labeled oligonucleotide probes with only one fluorophore. This review summarizes recent research on single-labeled oligonucleotide probes that exhibit fluorescence changes after encountering target nucleic acids, such as guanine-quenching probes, cyanine-containing probes, probes containing a fluorophore-labeled base, and microenvironment-sensitive probes.

  19. Automatic single- and multi-label enzymatic function prediction by machine learning

    Directory of Open Access Journals (Sweden)

    Shervine Amidi

    2017-03-01

    Full Text Available The number of protein structures in the PDB database has been increasing more than 15-fold since 1999. The creation of computational models predicting enzymatic function is of major importance since such models provide the means to better understand the behavior of newly discovered enzymes when catalyzing chemical reactions. Until now, single-label classification has been widely performed for predicting enzymatic function limiting the application to enzymes performing unique reactions and introducing errors when multi-functional enzymes are examined. Indeed, some enzymes may be performing different reactions and can hence be directly associated with multiple enzymatic functions. In the present work, we propose a multi-label enzymatic function classification scheme that combines structural and amino acid sequence information. We investigate two fusion approaches (in the feature level and decision level and assess the methodology for general enzymatic function prediction indicated by the first digit of the enzyme commission (EC code (six main classes on 40,034 enzymes from the PDB database. The proposed single-label and multi-label models predict correctly the actual functional activities in 97.8% and 95.5% (based on Hamming-loss of the cases, respectively. Also the multi-label model predicts all possible enzymatic reactions in 85.4% of the multi-labeled enzymes when the number of reactions is unknown. Code and datasets are available at https://figshare.com/s/a63e0bafa9b71fc7cbd7.

  20. Measurement of the equivalent dose in quartz using a regenerative-dose single-aliquot protocol

    International Nuclear Information System (INIS)

    Murray, A.S.; Roberts, R.G.

    1998-01-01

    The principles behind a regenerative-dose single-aliquot protocol are outlined. It is shown for three laboratory-bleached Australian sedimentary quartz samples that the relative change in sensitivity of the optically stimulated luminescence (OSL) during a repeated measurement cycle (consisting of a dose followed by a 10 s preheat at a given temperature and then a 100 s exposure to blue/green light at 125 deg. C) is very similar to that of the 110 deg. C thermoluminescence (TL) peak measured during the preheat cycle. The absolute change in the TL sensitivity with preheat temperature is different for samples containing a natural or a regenerative dose. Furthermore, the absolute change in sensitivity in both the OSL and TL signals is non-linear with regeneration cycle, but the relative change in the OSL signal compared to the following 110 deg. C TL measurement is well approximated by a straight line. Both signals are thought to use the same luminescence centres, and so some common behaviour is not unexpected. A new regenerative-dose protocol is presented which makes use of this linear relationship to correct for sensitivity changes with regeneration cycle, and requires only one aliquot for the estimation of the equivalent dose (D e ). The protocol has been applied to quartz from nine Australian sites. To illustrate the value of the regenerative-dose single-aliquot approach, the apparent values of D e for 13 samples, containing doses of between 0.01 and 100 Gy, have been measured at various preheat temperatures of between 160 and 300 deg. C, using a single aliquot for each D e measurement. Excellent agreement is found between these single-aliquot estimates of D e and those obtained from additive-dose multiple-aliquot and single-aliquot protocols, over the entire dose range

  1. A single-aliquot OSL protocol using bracketing regenerative doses to accurately determine equivalent doses in quartz

    CERN Document Server

    Folz, E

    1999-01-01

    In most cases, sediments show inherent heterogeneity in their luminescence behaviours and bleaching histories, and identical aliquots are not available: single-aliquot determination of the equivalent dose (ED) is then the approach of choice and the advantages of using regenerative protocols are outlined. Experiments on five laboratory bleached and dosed quartz samples, following the protocol described by Murray and Roberts (1998. Measurement of the equivalent dose in quartz using a regenerative-dose single aliquot protocol. Radiation Measurements 27, 171-184), showed the hazards of using a single regeneration dose: a 10% variation in the regenerative dose yielded some equivalent dose estimates that differed from the expected value by more than 5%. A protocol is proposed that allows the use of different regenerative doses to bracket the estimated equivalent dose. The measured ED is found to be in excellent agreement with the known value when the main regeneration dose is within 10% of the true equivalent dose.

  2. A single-aliquot OSL protocol using bracketing regenerative doses to accurately determine equivalent doses in quartz

    International Nuclear Information System (INIS)

    Folz, Elise; Mercier, Norbert

    1999-01-01

    In most cases, sediments show inherent heterogeneity in their luminescence behaviours and bleaching histories, and identical aliquots are not available: single-aliquot determination of the equivalent dose (ED) is then the approach of choice and the advantages of using regenerative protocols are outlined. Experiments on five laboratory bleached and dosed quartz samples, following the protocol described by Murray and Roberts (1998. Measurement of the equivalent dose in quartz using a regenerative-dose single aliquot protocol. Radiation Measurements 27, 171-184), showed the hazards of using a single regeneration dose: a 10% variation in the regenerative dose yielded some equivalent dose estimates that differed from the expected value by more than 5%. A protocol is proposed that allows the use of different regenerative doses to bracket the estimated equivalent dose. The measured ED is found to be in excellent agreement with the known value when the main regeneration dose is within 10% of the true equivalent dose

  3. A phase 2a randomized, parallel group, dose-ranging study of molindone in children with attention-deficit/hyperactivity disorder and persistent, serious conduct problems.

    Science.gov (United States)

    Stocks, Jennifer Dugan; Taneja, Baldeo K; Baroldi, Paolo; Findling, Robert L

    2012-04-01

    To evaluate safety and tolerability of four doses of immediate-release molindone hydrochloride in children with attention-deficit/hyperactivity disorder (ADHD) and serious conduct problems. This open-label, parallel-group, dose-ranging, multicenter trial randomized children, aged 6-12 years, with ADHD and persistent, serious conduct problems to receive oral molindone thrice daily for 9-12 weeks in four treatment groups: Group 1-10 mg (5 mg if weight conduct problems. Secondary outcome measures included change in Nisonger Child Behavior Rating Form-Typical Intelligence Quotient (NCBRF-TIQ) Conduct Problem subscale scores, change in Clinical Global Impressions-Severity (CGI-S) and -Improvement (CGI-I) subscale scores from baseline to end point, and Swanson, Nolan, and Pelham rating scale-revised (SNAP-IV) ADHD-related subscale scores. The study randomized 78 children; 55 completed the study. Treatment with molindone was generally well tolerated, with no clinically meaningful changes in laboratory or physical examination findings. The most common treatment-related adverse events (AEs) included somnolence (n=9), weight increase (n=8), akathisia (n=4), sedation (n=4), and abdominal pain (n=4). Mean weight increased by 0.54 kg, and mean body mass index by 0.24 kg/m(2). The incidence of AEs and treatment-related AEs increased with increasing dose. NCBRF-TIQ subscale scores improved in all four treatment groups, with 34%, 34%, 32%, and 55% decreases from baseline in groups 1, 2, 3, and 4, respectively. CGI-S and SNAP-IV scores improved over time in all treatment groups, and CGI-I scores improved to the greatest degree in group 4. Molindone at doses of 5-20 mg/day (children weighing <30 kg) and 20-40 mg (≥ 30 kg) was well tolerated, and preliminary efficacy results suggest that molindone produces dose-related behavioral improvements over 9-12 weeks. Additional double-blind, placebo-controlled trials are needed to further investigate molindone in this pediatric population.

  4. Safety of a new compact catheter for men with neurogenic bladder dysfunction: a randomised, crossover and open-labelled study

    DEFF Research Database (Denmark)

    Chartier-Kastler, E; Lauge, I; Ruffion, A

    2011-01-01

    Self-catheterising males aged =18 years with spinal cord lesion and normal/impaired urethral sensation were enrolled in this comparative, randomised, crossover and open-labelled multicentre trial.......Self-catheterising males aged =18 years with spinal cord lesion and normal/impaired urethral sensation were enrolled in this comparative, randomised, crossover and open-labelled multicentre trial....

  5. Pharmacokinetics of 111In-labeled anti-p97 monoclonal antibody in patients with metastatic malignant melanoma

    International Nuclear Information System (INIS)

    Rosenblum, M.G.; Murray, J.L.; Haynie, T.P.; Glenn, H.J.; Jahns, M.F.; Benjamin, R.S.; Frincke, J.M.; Carlo, D.J.; Hersh, E.M.

    1985-01-01

    Twenty-eight patients with metastatic malignant melanoma received anti-p97 murine monoclonal antibody (96.5) infused over 2 h at doses between 1 and 20 mg coupled to either 2.5 or 5.0 mCi of 111 In by the bifunctional chelating agent diethyltriaminepentaacetic acid. Clearance of 111 In from plasma closely fit an open, one-compartment mathematical model (r2 greater than 0.90). The overall half-life of 111 In plasma was approximately 31 h and did not appear to be dependent on the total dose of antibody administered. The apparent volume of distribution of the 111 In label approximated the total blood volume (7.8 +/- 0.7 liters) at the 1-mg dose and decreased to 3.0 +/- 0.14 liters at the 20-mg dose, suggesting saturation of antigenic or other extravascular binding sites at higher antibody doses. The clearance of the murine monoclonal antibody itself from plasma was measured by an enzyme-linked immunosorbent assay. The pharmacokinetics for the murine antibody in plasma also fit an open, one-compartment mathematical model. All pharmacokinetic parameters for unlabeled antibody closely paralleled those found for 111 In-labeled antibody pharmacokinetics. This suggests that the 111 In radiolabel remains complexed to the monoclonal antibody after in vivo administration. The cumulative urinary excretion of the 111 In label over 48 h was between 12 and 23% of the total administered dose and is assumed to represent 111 In-labeled chelate complex unattached to antibody. Analysis of the 111 In label in spleen, liver, heart, and kidney showed that the concentration of label in liver tissue was reduced with increasing antibody doses and coincided with changes in the apparent volume of distribution

  6. Oxytocin efficacy is modulated by dosage and oxytocin receptor genotype in young adults with high-functioning autism: a 24-week randomized clinical trial.

    Science.gov (United States)

    Kosaka, H; Okamoto, Y; Munesue, T; Yamasue, H; Inohara, K; Fujioka, T; Anme, T; Orisaka, M; Ishitobi, M; Jung, M; Fujisawa, T X; Tanaka, S; Arai, S; Asano, M; Saito, D N; Sadato, N; Tomoda, A; Omori, M; Sato, M; Okazawa, H; Higashida, H; Wada, Y

    2016-08-23

    Recent studies have suggested that long-term oxytocin administration can alleviate the symptoms of autism spectrum disorder (ASD); however, factors influencing its efficacy are still unclear. We conducted a single-center phase 2, pilot, randomized, double-blind, placebo-controlled, parallel-group, clinical trial in young adults with high-functioning ASD, to determine whether oxytocin dosage and genetic background of the oxytocin receptor affects oxytocin efficacy. This trial consisted of double-blind (12 weeks), open-label (12 weeks) and follow-up phases (8 weeks). To examine dose dependency, 60 participants were randomly assigned to high-dose (32 IU per day) or low-dose intranasal oxytocin (16 IU per day), or placebo groups during the double-blind phase. Next, we measured single-nucleotide polymorphisms (SNPs) in the oxytocin receptor gene (OXTR). In the intention-to-treat population, no outcomes were improved after oxytocin administration. However, in male participants, Clinical Global Impression-Improvement (CGI-I) scores in the high-dose group, but not the low-dose group, were significantly higher than in the placebo group. Furthermore, we examined whether oxytocin efficacy, reflected in the CGI-I scores, is influenced by estimated daily dosage and OXTR polymorphisms in male participants. We found that >21 IU per day oxytocin was more effective than ⩽21 IU per day, and that a SNP in OXTR (rs6791619) predicted CGI-I scores for ⩽21 IU per day oxytocin treatment. No severe adverse events occurred. These results suggest that efficacy of long-term oxytocin administration in young men with high-functioning ASD depends on the oxytocin dosage and genetic background of the oxytocin receptor, which contributes to the effectiveness of oxytocin treatment of ASD.

  7. A randomized clinical trial with two doses of an enteral diabetes-specific suplements in elderly patients with diabetes mellitus type 2.

    Science.gov (United States)

    de Luis, D A; Izaola, O; de la Fuente, B; Terroba, M C; Cuellar, L; Cabezas, G

    2013-06-01

    The aim of our study was to investigate whether two different daily doses of a high monounsaturated fatty acid (MUFA) specific diabetes enteral formula could improve nutritional variables as well as metabolic parameters. We conducted a randomized, open-label, multicenter, parallel group study. 27 patients with diabetes mellitus type 2 with recent weight loss were randomized to one of two study groups: group 1 (two cans per day) and group 2 (three cans per day) for a ten week period. A significative decrease of HbA1c was detected in both groups. The decrease 0.98% (confidence interval 95% 0.19-1.88) was higher in group 2 than group 1 0.60% (confidence interval 95% 0.14-1.04). A significant increase of weight, body mass index, fat mass, albumin, prealbumin and transferrin was observed in both groups without statistical differences in this improvement between both groups. The increase of weight 4.59kg (confidence interval 95% 1.71-9.49) was higher in group 2 than group 1 1.46% (confidence interval 95% 0.39-2.54). Gastrointestinal tolerance (diarrhea episodes) with both formulas was good, without statistical differences (7.60% vs 7.14%: ns). A high monounsaturated fatty acid diabetes-specific supplement improved HbA1c and nutritional status. These improvements were higher with three supplements than with two per day.

  8. Single-Dose Lignocaine-Based Blood Cardioplegia in Single Valve Replacement Patients

    Directory of Open Access Journals (Sweden)

    Jaydip Ramani

    Full Text Available Abstract OBJECTIVE: Myocardial protection is the most important in cardiac surgery. We compared our modified single-dose long-acting lignocaine-based blood cardioplegia with short-acting St Thomas 1 blood cardioplegia in patients undergoing single valve replacement. METHODS: A total of 110 patients who underwent single (aortic or mitral valve replacement surgery were enrolled. Patients were divided in two groups based on the cardioplegia solution used. In group 1 (56 patients, long-acting lignocaine based-blood cardioplegia solution was administered as a single dose while in group 2 (54 patients, standard St Thomas IB (short-acting blood-based cardioplegia solution was administered and repeated every 20 minutes. All the patients were compared for preoperative baseline parameters, intraoperative and all the postoperative parameters. RESULTS: We did not find any statistically significant difference in preoperative baseline parameters. Cardiopulmonary bypass time were 73.8±16.5 and 76.4±16.9 minutes (P=0.43 and cross clamp time were 58.9±10.3 and 66.3±11.2 minutes (P=0.23 in group 1 and group 2, respectively. Mean of maximum inotrope score was 6.3±2.52 and 6.1±2.13 (P=0.65 in group 1 and group 2, respectively. We also did not find any statistically significant difference in creatine-phosphokinase-MB (CPK-MB, Troponin-I levels, lactate level and cardiac functions postoperatively. CONCLUSION: This study proves the safety and efficacy of long-acting lignocaine-based single-dose blood cardioplegia compared to the standard short-acting multi-dose blood cardioplegia in patients requiring the single valve replacement. Further studies need to be undertaken to establish this non-inferiority in situations of complex cardiac procedures especially in compromised patients.

  9. A single-center, prospective, randomized, open-label, clinical trial of ceramide 2-containing hydrocolloid dressings versus polyurethane film dressings for pressure ulcer prevention in high-risk surgical patients

    Directory of Open Access Journals (Sweden)

    Kohta M

    2015-11-01

    Full Text Available Masushi Kohta,1 Kazumi Sakamoto,2 Yasuhiro Kawachi,3 Tsunao Oh-i4 1Medical Engineering Laboratory, ALCARE Co, Ltd, Tokyo, 2Department of Nursing, 3Department of Dermatology, Tokyo Medical University Ibaraki Medical Center, Ibaraki, 4Department of Dermatology, Tokyo Medical University Hachioji Medical Center, Tokyo, Japan Purpose: There have been previous clinical studies regarding the impact of dressings on the prevention of pressure ulcer development. However, it remains unclear whether one type of dressing is better than any other type for preventing ulcer development during surgery. Therefore, we compared the effects of ceramide 2-containing hydrocolloid dressing with film dressings in high-risk patients with regard to reducing the incidence of pressure ulcer development during surgery. Patients and methods: A prospective, randomized, open-label, clinical trial was conducted involving patients who were at a high risk of developing pressure ulcers at a Japanese hospital. The intervention group received ceramide 2-containing hydrocolloid dressings (n=66, and the control group received film dressings (n=64. The primary end point was the incidence rate of pressure ulcer development in both groups; skin damage, such as blanchable erythema, skin discoloration, contact dermatitis, and stripped skin, was recorded as the secondary end point. The relative risk (RR and 95% confidence interval (CI were assessed to compare the probability ratios of pressure ulcer development between the groups. Results: There were significantly fewer patients who developed pressure ulcers in the intervention group than in the control group (RR, 0.37; 95% CI, 0.05–0.99; P=0.04. In the post hoc subgroup analysis, the superiority of the intervention group was more marked when patients had a lower body mass index (P=0.02, lower albumin values (P=0.07, and operation time of 3 hours or more and less than 6 hours (P=0.03. There was no evidence of any statistically significant

  10. Effect of the angiotensin receptor-neprilysin inhibitor sacubitril/valsartan on the pharmacokinetics and pharmacodynamics of a single dose of furosemide.

    Science.gov (United States)

    Ayalasomayajula, Surya; Schuehly, Uwe; Pal, Parasar; Chen, Fabian; Zhou, Wei; Sunkara, Gangadhar; Langenickel, Thomas H

    2018-05-01

    Sacubitril/valsartan is indicated for the treatment of heart failure and reduced ejection fraction (HFrEF). Furosemide, a loop diuretic commonly used for the treatment of HFrEF, may be coadministered with sacubitril/valsartan in clinical practice. The effect of sacubitril/valsartan on the pharmacokinetics and pharmacodynamics of furosemide was evaluated in this open label, two-period, single-sequence study in healthy subjects. All subjects (n = 28) received 40 mg oral single-dose furosemide during period 1, followed by a washout of 2 days. In period 2, sacubitril/valsartan 200 mg (97/103 mg) was administered twice daily for 5 days and a single dose of 40 mg furosemide was coadministered on day 6. Serial plasma and urine samples were collected to determine the pharmacokinetics of furosemide and sacubitril/valsartan and the pharmacodynamics of furosemide. The point estimates and the associated 90% confidence intervals for pharmacokinetic parameters were evaluated. Coadministration of furosemide with sacubitril/valsartan decreased the maximum observed plasma concentration (C max ) [estimated geometric mean ratio (90% confidence interval): 0.50 (0.44, 0.56)], area under the plasma concentration-time curve (AUC) from time 0 to infinity [0.72 (0.67, 0.77)] and 24-h urinary excretion of furosemide [0.74 (0.69, 0.79)]. When coadministered with sacubitril/valsartan, 0-4-h, 4-8-h and 0-24-h diuresis in response to furosemide was reduced by ~7%, 21% and 0.2%, respectively, while natriuresis was reduced by ~ 28.5%, 7% and 15%, respectively. Post hoc analysis of the pivotal phase III Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF) indicated that the median furosemide dose was similar at baseline and at the end of the study in the sacubitril/valsartan group. Sacubitril/valsartan reduced plasma C max and AUC and 24-h urinary excretion of furosemide, while not significantly affecting its

  11. Safety of a new compact catheter for men with neurogenic bladder dysfunction: a randomised, crossover and open-labelled study

    DEFF Research Database (Denmark)

    Chartier-Kastler, E; Lauge, I; Ruffion, A

    2011-01-01

    Self-catheterising males aged ≥18 years with spinal cord lesion and normal/impaired urethral sensation were enrolled in this comparative, randomised, crossover and open-labelled multicentre trial.......Self-catheterising males aged ≥18 years with spinal cord lesion and normal/impaired urethral sensation were enrolled in this comparative, randomised, crossover and open-labelled multicentre trial....

  12. Pharmacokinetic properties and tolerability of low-dose SoluMatrix diclofenac.

    Science.gov (United States)

    Desjardins, Paul J; Olugemo, Kemi; Solorio, Daniel; Young, Clarence L

    2015-02-01

    This study compared the pharmacokinetic properties and safety profile of low-dose (18- and 35-mg) diclofenac capsules manufactured using SoluMatrix Fine Particle Technology (Trademark of iCeutica Inc. (Philadelphia, Pennsylvania), and the technology is licensed to Iroko Pharmaceuticals, LLC (Philadelphia, Pennsylvania) for exclusive use in NSAIDs), which produces submicron-sized drug particles with enhanced dissolution properties, to those of diclofenac potassium immediate-release (IR) 50-mg tablets. This Phase 1, single-center, randomized, open-label, single-dose crossover study was conducted in 40 healthy volunteers. Subjects received, in randomized order, SoluMatrix diclofenac 18- or 35-mg capsules in the fasting condition, SoluMatrix diclofenac 35-mg capsules under fed conditions, and diclofenac potassium IR 50-mg tablets under fasting and fed conditions. Pharmacokinetic parameters (T(max), C(max), AUC(0-t), AUC(0-∞)) were calculated from the concentrations of diclofenac in the plasma. Absorption, food effect, and dose proportionality were determined using a mixed-model ANOVA for C(max), AUC(0-t), AUC(0-∞). Tolerability was assessed by recording adverse events, physical examination findings, vital sign measurements: clinical laboratory test results. Overall, 35 healthy volunteers aged 18 to 52 years completed the study. The mean age of the subjects was 33.4 years, and approximately half were men (47.5%). Median T(max) values were similar between the low-dose SoluMatrix diclofenac 35-mg capsules and the diclofenac potassium IR 50-mg tablets (both, ~1.0 hour). The mean maximum plasma concentration (C(max)) after the administration of low-dose SoluMatrix diclofenac 35-mg capsules was 26% lower than that with diclofenac potassium IR 50-mg tablets under fasting conditions (868.72 vs 1194.21 ng/mL). The administration of low-dose SoluMatrix diclofenac 35-mg capsules was associated with a 23% lower overall systemic exposure compared with that of diclofenac

  13. An open-label extension long-term study of the safety and efficacy of aripiprazole for irritability in children and adolescents with autistic disorder in Japan.

    Science.gov (United States)

    Ichikawa, Hironobu; Hiratani, Michio; Yasuhara, Akihiro; Tsujii, Noa; Oshimo, Takashi; Ono, Hiroaki; Tadori, Yoshihiro

    2018-02-01

    The purpose of this study was to evaluate the long-term safety and efficacy of aripiprazole in treating irritability in pediatric patients (6-17 years) with autistic disorder (AD) in Japan. In this open-label extension study, patients who had completed a previous randomized, double-blind, placebo-controlled 8-week study were enrolled and were flexibly dosed with aripiprazole (1-15 mg/day) until the new indication of irritability in pediatric autism spectrum disorder was approved in Japan. Seventy (81%) out of 86 enrolled patients completed week-48 assessments. The mean duration of treatment was 694.9 days. The mean daily dose of aripiprazole over the treatment period was 7.2 mg and the mean of the final dose was 8.5 mg. The most common treatment-emergent adverse events (TEAE; ≥20%) included nasopharyngitis, somnolence, influenza, and increased weight. The majority of these TEAE were mild or moderate in severity, and there were no deaths, and no clinically relevant findings in laboratory values except prolactin decrease, vital signs, height, or ECG parameters. At week 48 (observed case), the mean change from baseline in the Irritability subscale score for the Aberrant Behavior Checklist Japanese Version was -6.3 in prior placebo patients and -2.6 in prior aripiprazole patients. Aripiprazole was generally safe, well tolerated, and effective in the long-term treatment of irritability associated with AD in Japanese pediatric patients. © 2017 The Authors. Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.

  14. Randomized Trial of 2 Versus 1 Dose of Measles Vaccine

    DEFF Research Database (Denmark)

    Brønd, Marie; Martins, Cesario L; Byberg, Stine

    2018-01-01

    Background: Two doses of measles vaccine (MV) might reduce the nonmeasles mortality rate more than 1 dose of MV does. The effect of 2 versus 1 dose on morbidity has not been examined. Within a randomized trial of the effect of 2 doses versus 1 dose of MV on mortality in Guinea-Bissau, we investig...

  15. Fixed-dose combinations of drugs versus single-drug formulations for treating pulmonary tuberculosis

    Science.gov (United States)

    Gallardo, Carmen R; Rigau Comas, David; Valderrama Rodríguez, Angélica; Roqué i Figuls, Marta; Parker, Lucy Anne; Caylà, Joan; Bonfill Cosp, Xavier

    2016-01-01

    Background People who are newly diagnosed with pulmonary tuberculosis (TB) typically receive a standard first-line treatment regimen that consists of two months of isoniazid, rifampicin, pyrazinamide, and ethambutol followed by four months of isoniazid and rifampicin. Fixed-dose combinations (FDCs) of these drugs are widely recommended. Objectives To compare the efficacy, safety, and acceptability of anti-tuberculosis regimens given as fixed-dose combinations compared to single-drug formulations for treating people with newly diagnosed pulmonary tuberculosis. Search methods We searched the Cochrane Infectious Disease Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL, published in the Cochrane Library, Issue 11 2015); MEDLINE (1966 to 20 November 2015); EMBASE (1980 to 20 November 2015); LILACS (1982 to 20 November 2015); the metaRegister of Controlled Trials; and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), without language restrictions, up to 20 November 2015. Selection criteria Randomized controlled trials that compared the use of FDCs with single-drug formulations in adults (aged 15 years or more) newly diagnosed with pulmonary TB. Data collection and analysis Two review authors independently assessed studies for inclusion, and assessed the risk of bias and extracted data from the included trials. We used risk ratios (RRs) for dichotomous data and mean differences (MDs) for continuous data with 95% confidence intervals (CIs). We attempted to assess the effect of treatment for time-to-event measures with hazard ratios and their 95% CIs. We used the Cochrane 'Risk of bias' assessment tool to determine the risk of bias in included trials. We used the fixed-effect model when there was little heterogeneity and the random-effects model with moderate heterogeneity. We used an I² statistic value of 75% or greater to denote significant heterogeneity, in which case we did not perform a

  16. Pharmacokinetics of [14C]teicoplanin in male rats after single intravenous dose

    International Nuclear Information System (INIS)

    Bernareggi, A.; Cavenaghi, L.; Assandri, A.

    1986-01-01

    The pharmacokinetic profile of [ 14 C]teicoplanin was studied in male Sprague-Dawley rats given a single 10,000-U/kg intravenous dose. The disposition of the antimicrobial activity in the body was estimated by a three-compartment open model. Plasma concentration data were fitted to a three-exponent equation. The profile of total 14 C in plasma was similar to that of the microbiological activity. The cumulative recovery of total 14 C 5 days after drug administration averaged 76.3% of the administered dose in the urine and 8.7% in the feces. The residual dose remaining in the animal carcasses was 11.1%. Teicoplanin was widely distributed in the body. In almost all organs, the maximum concentration of [ 14 C]teicoplanin was already reached at the first time of killing, which was 0.25 h after the administration of drug. The liver, kidneys, skin, and fat contained most of the residual dose found in the animal carcasses 120 h after administration and behaved as a deep compartment with the adrenal glands and spleen

  17. Single dose silodosin prior to voiding cystourethrogram: a pharmacological adjunct to enhance visualization of posterior urethra.

    Science.gov (United States)

    Nagathan, Deepak Sharanappa; Dalela, Divakar; Sankhwar, Satyanarayan; Goel, Apul; Dwivedi, Amod Kumar; Yadav, Rahul

    2014-03-04

    Voiding cystourethrogram (VCUG) is needed to ascertain the upper end of urethral stricture. Occasionally, a patient is unable to open the bladder neck with resultant failure of the test. Realizing the strong and prompt alpha antagonistic action of silodosin, we evaluated single 8 mg dose as a pharmacological adjunct prior to VCUG to overcome this problem.

  18. An Open-Label, Randomized Trial of Methylphenidate and Atomoxetine Treatment in Children with Attention-Deficit/Hyperactivity Disorder.

    Science.gov (United States)

    Shang, Chi-Yung; Pan, Yi-Lei; Lin, Hsiang-Yuan; Huang, Lin-Wan; Gau, Susan Shur-Fen

    2015-09-01

    The efficacy of both methylphenidate and atomoxetine has been established in placebo-controlled trials. The present study aimed to directly compare the efficacy of methylphenidate and atomoxetine in improving symptoms among children with attention-deficit/hyperactivity disorder (ADHD). The study sample included 160 drug-naïve children and adolescents 7-16 years of age, with DSM-IV-defined ADHD, randomly assigned to osmotic-release oral system methylphenidate (OROS-methylphenidate) (n=80) and atomoxetine (n=80) in a 24 week, open-label, head-to-head clinical trial. The primary efficacy measure was the score of the ADHD Rating Scale-IV Parents Version: Investigator Administered and Scored (ADHD-RS-IV). The secondary efficacy measures included the Clinical Global Impressions-ADHD-Severity (CGI-ADHD-S) and Chinese Swanson, Nolan, and Pelham IV scale (SNAP-IV), based on the ratings of investigators, parents, teachers, and subjects. At week 24, mean changes in ADHD-RS-IV Inattention scores were 13.58 points (Cohen's d, -3.08) for OROS-methylphenidate and 12.65 points (Cohen's d, -3.05) for atomoxetine; and mean changes in ADHD-RS-IV Hyperactivity-Impulsivity scores were 10.16 points (Cohen's d, -1.75) for OROS-methylphenidate and 10.68 points (Cohen's d, -1.87) for atomoxetine. In terms of parent-, teacher-, and self-ratings on behavioral symptoms, both of the two treatment groups significantly decreased on the SNAP-IV scores at the end-point, with effect sizes ranging from 0.9 to 0.96 on the Inattention subscale and from 0.61 to 0.8 on the Hyperactivity/Impulsivity subscale for OROS-methylphenidate; and from 0.51 to 0.88 on the Inattention subscale and from 0.29 to 0.57 on the Hyperactivity/Impulsivity subscale for atomoxetine. No statistically significant differences between treatment groups were observed on the outcome measures. Vomiting, somnolence, and dizziness were reported more often for atomoxetine than for OROS-methylphenidate, whereas insomnia was reported

  19. A randomized trial of obeticholic acid monotherapy in patients with primary biliary cholangitis.

    Science.gov (United States)

    Kowdley, Kris V; Luketic, Velimir; Chapman, Roger; Hirschfield, Gideon M; Poupon, Raoul; Schramm, Christoph; Vincent, Catherine; Rust, Christian; Parés, Albert; Mason, Andrew; Marschall, Hanns-Ulrich; Shapiro, David; Adorini, Luciano; Sciacca, Cathi; Beecher-Jones, Tessa; Böhm, Olaf; Pencek, Richard; Jones, David

    2018-05-01

    Obeticholic acid (OCA), a potent farnesoid X receptor agonist, was studied as monotherapy in an international, randomized, double-blind, placebo-controlled phase 2 study in patients with primary biliary cholangitis who were then followed for up to 6 years. The goals of the study were to assess the benefit of OCA in the absence of ursodeoxycholic acid, which is relevant for patients who are intolerant of ursodeoxycholic acid and at higher risk of disease progression. Patients were randomized and dosed with placebo (n = 23), OCA 10 mg (n = 20), or OCA 50 mg (n = 16) given as monotherapy once daily for 3 months (1 randomized patient withdrew prior to dosing). The primary endpoint was the percent change in alkaline phosphatase from baseline to the end of the double-blind phase of the study. Secondary and exploratory endpoints included change from baseline to month 3/early termination in markers of cholestasis, hepatocellular injury, and farnesoid X receptor activation. Efficacy and safety continue to be monitored through an ongoing 6-year open-label extension (N = 28). Alkaline phosphatase was reduced in both OCA groups (median% [Q1, Q3], OCA 10 mg -53.9% [-62.5, -29.3], OCA 50 mg -37.2% [-54.8, -24.6]) compared to placebo (-0.8% [-6.4, 8.7]; P OCA improved many secondary and exploratory endpoints (including γ-glutamyl transpeptidase, alanine aminotransferase, conjugated bilirubin, and immunoglobulin M). Pruritus was the most common adverse event; 15% (OCA 10 mg) and 38% (OCA 50 mg) discontinued due to pruritus. OCA monotherapy significantly improved alkaline phosphatase and other biochemical markers predictive of improved long-term clinical outcomes. Pruritus increased dose-dependently with OCA treatment. Biochemical improvements were observed through 6 years of open-label extension treatment. (Hepatology 2018;67:1890-1902). © 2017 The Authors. Hepatology published by Wiley Periodicals, Inc. on behalf of American Association for the Study of Liver Diseases.

  20. Safety of telmisartan in patients with arterial hypertension - An open-label observational study

    NARCIS (Netherlands)

    Michel, Martin C.; Bohner, Herbert; Köster, Jürgen; Schäfers, Rafael; Heemann, Uwe

    2004-01-01

    Objective: To determine whether age, gender, concomitant disease and/or previous or present antihypertensive medication affect the safety or antihypertensive efficacy of telmisartan in the treatment of arterial hypertension. Study Design and Methods: In this large-scale, open-label postmarketing

  1. Ibuprofen plus paracetamol versus ibuprofen in acute low back pain: a randomized open label multicenter clinical study

    Directory of Open Access Journals (Sweden)

    Predrag Ostojic

    2017-01-01

    Full Text Available Objective: to estimate whether combination of ibuprofen and paracetamol is more effective than ibuprofen in monotherapy, in the treatment of acute low back pain. Methods: 80 adult patients with acute low back pain were randomized into two subgroups. In the first subgroup, 40 patients were treated with ibuprofen 400mg three times a day (TID, whilst patients in the second subgroup (n=40 were treated with a fixed-dose combination tablet of ibuprofen 200mg plus paracetamol 325mg TID, for three consecutive days. Patients were followed for another 7 days. Efficacy and tolerability of both treatment options was assessed. Results: A statistically significant decrease in pain intensity, assessed using a visual analogue scale (p

  2. Preliminary results for avelumab plus axitinib as first-line therapy in patients with advanced clear-cell renal-cell carcinoma (JAVELIN Renal 100): an open-label, dose-finding and dose-expansion, phase 1b trial.

    Science.gov (United States)

    Choueiri, Toni K; Larkin, James; Oya, Mototsugu; Thistlethwaite, Fiona; Martignoni, Marcella; Nathan, Paul; Powles, Thomas; McDermott, David; Robbins, Paul B; Chism, David D; Cho, Daniel; Atkins, Michael B; Gordon, Michael S; Gupta, Sumati; Uemura, Hirotsugu; Tomita, Yoshihiko; Compagnoni, Anna; Fowst, Camilla; di Pietro, Alessandra; Rini, Brian I

    2018-04-01

    The combination of an immune checkpoint inhibitor and a VEGF pathway inhibitor to treat patients with advanced renal-cell carcinoma might increase the clinical benefit of these drugs compared with their use alone. Here, we report preliminary results for the combination of avelumab, an IgG1 monoclonal antibody against the programmed cell death protein ligand PD-L1, and axitinib, a VEGF receptor inhibitor approved for second-line treatment of advanced renal-cell carcinoma, in treatment-naive patients with advanced renal-cell carcinoma. The JAVELIN Renal 100 study is an ongoing open-label, multicentre, dose-finding, and dose-expansion, phase 1b study, done in 14 centres in the USA, UK, and Japan. Eligible patients were aged 18 years or older (≥20 years in Japan) and had histologically or cytologically confirmed advanced renal-cell carcinoma with clear-cell component, life expectancy of at least 3 months, an Eastern Cooperative Oncology Group performance status of 1 or less, received no previous systemic treatment for advanced renal cell carcinoma, and had a resected primary tumour. Patients enrolled into the dose-finding phase received 5 mg axitinib orally twice daily for 7 days, followed by combination therapy with 10 mg/kg avelumab intravenously every 2 weeks and 5 mg axitinib orally twice daily. Based on the pharmacokinetic data from the dose-finding phase, ten additional patients were enrolled into the dose-expansion phase and assigned to this regimen. The other patients in the dose-expansion phase started taking combination therapy directly. The primary endpoint was dose-limiting toxicities in the first 4 weeks (two cycles) of treatment with avelumab plus axitinib. Safety and antitumour activity analyses were done in all patients who received at least one dose of avelumab or axitinib. This trial is registered with ClinicalTrials.gov, number NCT02493751. Between Oct 30, 2015, and Sept 30, 2016, we enrolled six patients into the dose-finding phase and 49 into the

  3. Subject-driven titration of biphasic insulin aspart 30 twice daily is non-inferior to investigator-driven titration in Chinese patients with type 2 diabetes inadequately controlled with premixed human insulin: A randomized, open-label, parallel-group, multicenter trial.

    Science.gov (United States)

    Yang, Wenying; Zhu, Lvyun; Meng, Bangzhu; Liu, Yu; Wang, Wenhui; Ye, Shandong; Sun, Li; Miao, Heng; Guo, Lian; Wang, Zhanjian; Lv, Xiaofeng; Li, Quanmin; Ji, Qiuhe; Zhao, Weigang; Yang, Gangyi

    2016-01-01

    The present study was to compare the efficacy and safety of subject-driven and investigator-driven titration of biphasic insulin aspart 30 (BIAsp 30) twice daily (BID). In this 20-week, randomized, open-label, two-group parallel, multicenter trial, Chinese patients with type 2 diabetes inadequately controlled by premixed/self-mixed human insulin were randomized 1:1 to subject-driven or investigator-driven titration of BIAsp 30 BID, in combination with metformin and/or α-glucosidase inhibitors. Dose adjustment was decided by patients in the subject-driven group after training, and by investigators in the investigator-driven group. Eligible adults (n = 344) were randomized in the study. The estimated glycated hemoglobin (HbA1c) reduction was 14.5 mmol/mol (1.33%) in the subject-driven group and 14.3 mmol/mol (1.31%) in the investigator-driven group. Non-inferiority of subject-titration vs investigator-titration in reducing HbA1c was confirmed, with estimated treatment difference -0.26 mmol/mol (95% confidence interval -2.05, 1.53) (-0.02%, 95% confidence interval -0.19, 0.14). Fasting plasma glucose, postprandial glucose increment and self-measured plasma glucose were improved in both groups without statistically significant differences. One severe hypoglycemic event was experienced by one subject in each group. A similar rate of nocturnal hypoglycemia (events/patient-year) was reported in the subject-driven (1.10) and investigator-driven (1.32) groups. There were 64.5 and 58.1% patients achieving HbA1c titration of BIAsp 30 BID was as efficacious and well-tolerated as investigator-titration. The present study supported patients to self-titrate BIAsp 30 BID under physicians' supervision.

  4. Open-label administration of lisdexamfetamine dimesylate improves executive function impairments and symptoms of attention-deficit/hyperactivity disorder in adults.

    Science.gov (United States)

    Brown, Thomas E; Brams, Matthew; Gao, Joseph; Gasior, Maria; Childress, Ann

    2010-09-01

    Executive function (EF) impairment in attention-deficit/hyperactivity disorder (ADHD) may account for behavioral symptoms such as poor concentration, impaired working memory, problems in shifting among tasks, and prioritizing and planning complex sets of tasks or completing long-term projects at work or school. Poor self-regulation and control of emotional behaviors frequently are seen in patients with ADHD. This study assessed EF behaviors in adults with ADHD at baseline and after 4 weeks of treatment with lisdexamfetamine dimesylate (LDX). Executive function behavior was assessed using the Brown Attention-Deficit Disorder Scale (BADDS) during the 4-week open-label dose-optimization phase prior to a 2-period, randomized, double-blind, placebo-controlled crossover study of LDX (30-70 mg/day). The ADHD Rating Scale IV (ADHD-RS-IV) with adult prompts assessed ADHD symptoms. Change in EF behavioral symptoms was evaluated based on week 4 BADDS total and cluster scores; analyses of shifts from baseline among subjects with BADDS scores < 50, 50 to 59, 60 to 69, and ≥ 70; and scores less than or greater than baseline 90% confidence range (eg, reliably improved or worsened, respectively). Treatment-emergent adverse events (TEAEs) were described. At week 4, BADDS total and cluster scores were reduced (ie, improved; all P < 0.0001 vs baseline [n = 127]). The ADHD-RS-IV with adult prompts scores also improved (all P < 0.0001 vs baseline). At week 4, 62.7% of subjects had a BADDS total score of < 50, and 78.9% were reliably improved; 1.4% were reliably worsened. Common TEAEs (≥ 5%) during the dose-optimization phase were decreased appetite (36.6%), dry mouth (30.3%), headache (19.7%), insomnia (18.3%), upper respiratory tract infection (9.9%), irritability (8.5%), nausea (7.7%), anxiety (5.6%), and feeling jittery (5.6%). Clinically optimized doses of LDX (30-70 mg/day) significantly improved EF behaviors in adults with ADHD. Treatment-emergent adverse events with LDX were

  5. Low-Dose Intravenous Immunoglobulin Treatment for Long-Standing Complex Regional Pain Syndrome: A Randomized Trial.

    Science.gov (United States)

    Goebel, Andreas; Bisla, Jatinder; Carganillo, Roy; Frank, Bernhard; Gupta, Rima; Kelly, Joanna; McCabe, Candy; Murphy, Caroline; Padfield, Nick; Phillips, Ceri; Sanders, Mark; Serpell, Mick; Shenker, Nick; Shoukrey, Karim; Wyatt, Lynne; Ambler, Gareth

    2017-10-03

    Two small trials suggest that low-dose intravenous immunoglobulin (IVIg) may improve the symptoms of complex regional pain syndrome (CRPS), a rare posttraumatic pain condition. To confirm the efficacy of low-dose IVIg compared with placebo in reducing pain during a 6-week period in adult patients who had CRPS from 1 to 5 years. 1:1 parallel, randomized, placebo-controlled, multicenter trial for 6 weeks, with an optional 6-week open extension. Patients were randomly assigned to 1 of 2 study groups between 27 August 2013 and 28 October 2015; the last patient completed follow-up on 21 March 2016. Patients, providers, researchers, and outcome assessors were blinded to treatment assignment. (ISRCTN42179756). 7 secondary and tertiary care pain management centers in the United Kingdom. 111 patients with moderate or severe CRPS of 1 to 5 years' duration. IVIg, 0.5 g/kg of body weight, or visually indistinguishable placebo of 0.1% albumin in saline on days 1 and 22 after randomization. The primary outcome was 24-hour average pain intensity, measured daily between days 6 and 42, on an 11-point (0- to 10-point) rating scale. Secondary outcomes were pain interference and quality of life. The primary analysis sample consisted of 108 eligible patients, 103 of whom had outcome data. Mean (average) pain scores were 6.9 points (SD, 1.5) for placebo and 7.2 points (SD, 1.3) for IVIg. The adjusted difference in means was 0.27 (95% CI, -0.25 to 0.80; P = 0.30), which excluded the prespecified, clinically important difference of -1.2. No statistically significant differences in secondary outcomes were found between the groups. In the open extension, 12 of the 67 patients (18%) who received 2 IVIg infusions had pain reduction of at least 2 points compared with their baseline score. Two patients in the blinded phase (1 in the placebo and 1 in the IVIg group) and 4 in the open IVIg phase had serious events. Results do not apply to patients who have had CRPS for less than 1 year or more

  6. A phase I, randomized, single-dose study evaluating the pharmacokinetic equivalence of biosimilar ABP 215 and bevacizumab in healthy adult men.

    Science.gov (United States)

    Markus, Richard; Chow, Vincent; Pan, Zhiying; Hanes, Vladimir

    2017-10-01

    This study compared the pharmacokinetic (PK) profiles of the proposed biosimilar ABP 215 with bevacizumab in healthy males. In this randomized, single-blind, single-dose, three-arm, parallel-group study, healthy subjects were randomized to receive ABP 215 (n = 68), bevacizumab (US) (n = 67), or bevacizumab (EU) (n = 67) 3 mg/kg intravenously. Primary endpoints were area under the serum concentration-time curve from time 0 extrapolated to infinity (AUC inf ) and the maximum observed concentration (C max ). Secondary endpoints included safety and immunogenicity. AUC inf and C max were similar across the three groups. Geometric means ratio (GMR) for C max and AUC inf , respectively, was 0.98 and 0.99 for ABP 215 versus bevacizumab (US); 1.03 and 0.96 for ABP 215 versus bevacizumab (EU); and 1.05 and 0.97 for bevacizumab (US) versus bevacizumab (EU). The 90% confidence intervals for the GMRs of AUC inf and C max were within the prespecified standard PK bioequivalence criteria of 0.80 to 1.25. The incidence of adverse events (AEs) was 47.1, 32.8, and 61.2% in the ABP 215, bevacizumab (US) and bevacizumab (EU) groups, respectively. When analyzed by investigational site, the incidence and severity of AEs were comparable in the ABP 215 and bevacizumab groups. There were no AEs leading to study discontinuation. No binding or neutralizing anti-drug anti-bodies was detected. This study demonstrated the PK similarity of ABP 215 to both bevacizumab (US) and bevacizumab (EU), and of bevacizumab (US) to bevacizumab (EU). Safety and tolerability were comparable between treatments and no subject developed binding or neutralizing anti-drug anti-bodies.

  7. Long-Term, Open-Label Safety and Efficacy of Atomoxetine in Adults with ADHD: Final Report of a 4-Year Study

    Science.gov (United States)

    Adler, Lenard A.; Spencer, Thomas J.; Williams, David W.; Moore, Rodney J.; Michelson, David

    2008-01-01

    Objective: Previously, data from 97 weeks of open-label atomoxetine treatment of adults with attention-deficit/hyperactivity disorder (ADHD) were reported. This final report of that study presents results from over 4 years of treatment. Method: Results were derived from the study of 384 patients (125 patients remaining in the open-label trial…

  8. Demonstrating quantum random with single photons

    International Nuclear Information System (INIS)

    Bronner, Patrick; Strunz, Andreas; Meyn, Jan-Peter; Silberhorn, Christine

    2009-01-01

    We present an experiment for education which demonstrates random transmission or reflection of heralded single photons on beam splitters. With our set-up, we can realize different quantum random experiments by appropriate settings of polarization rotators. The concept of entanglement is motivated by correlated randomness. The experiments are suitable for undergraduate education and are available as interactive screen experiments.

  9. Once-daily omeprazole/sodium bicarbonate heals severe refractory reflux esophagitis with morning or nighttime dosing.

    Science.gov (United States)

    Orbelo, Diana M; Enders, Felicity T; Romero, Yvonne; Francis, Dawn L; Achem, Sami R; Dabade, Tushar S; Crowell, Michael D; Geno, Debra M; DeJesus, Ramona S; Namasivayam, Vikneswaran; Adamson, Steven C; Arora, Amindra S; Majka, Andrew J; Alexander, Jeffrey A; Murray, Joseph A; Lohse, Matthew; Diehl, Nancy N; Fredericksen, Mary; Jung, Kee Wook; Houston, Margaret S; O'Neil, Angela E; Katzka, David A

    2015-01-01

    Morning dose or twice-daily proton pump inhibitor (PPI) use is often prescribed to heal severe reflux esophagitis. Compare the effect of single dose morning (control arm) versus nighttime (experimental arm) omeprazole/sodium bicarbonate (Zegerid(®)) (IR-OME) on esophagitis and gastroesophageal reflux symptoms. Adult outpatients with Los Angeles grade C or D esophagitis were allocated to open-label 40 mg IR-OME once a day for 8 weeks in a prospective, randomized, parallel design, single center study. Esophagogastroduodenoscopy (EGD) and validated self-report symptom questionnaires were completed at baseline and follow-up. Intention-to-treat and per-protocol analyses were performed. Ninety-two of 128 (72 %) eligible subjects participated [64 (70 %) male, mean age 58 (range 19-86), median BMI 29 (range 21-51), 58 C:34 D]. Overall, 81 (88 %) subjects healed [n = 70 (76 %)] or improved [n = 11 (12 %)] erosions. There was no significant difference (morning vs. night) in mucosal healing [81 vs. 71 %, (p = 0.44)] or symptom resolution [heartburn (77 vs. 65 %, p = 0.12), acid regurgitation (82 vs. 73 %, p = 0.28)]. Prevalence of newly identified Barrett's esophagus was 14 % with half diagnosed only after treatment. Once-daily IR-OME (taken morning or night) effectively heals severe reflux esophagitis and improves GERD symptoms. Results support the clinical practice recommendation to repeat EGD after 8 weeks PPI therapy in severe esophagitis patients to assure healing and exclude Barrett's esophagus.

  10. Methadone continuation versus forced withdrawal on incarceration in a combined US prison and jail: a randomised, open-label trial.

    Science.gov (United States)

    Rich, Josiah D; McKenzie, Michelle; Larney, Sarah; Wong, John B; Tran, Liem; Clarke, Jennifer; Noska, Amanda; Reddy, Manasa; Zaller, Nickolas

    2015-07-25

    Methadone is an effective treatment for opioid dependence. When people who are receiving methadone maintenance treatment for opioid dependence are incarcerated in prison or jail, most US correctional facilities discontinue their methadone treatment, either gradually, or more often, abruptly. This discontinuation can cause uncomfortable symptoms of withdrawal and renders prisoners susceptible to relapse and overdose on release. We aimed to study the effect of forced withdrawal from methadone upon incarceration on individuals' risk behaviours and engagement with post-release treatment programmes. In this randomised, open-label trial, we randomly assigned (1:1) inmates of the Rhode Island Department of Corrections (RI, USA) who were enrolled in a methadone maintenance-treatment programme in the community at the time of arrest and wanted to remain on methadone treatment during incarceration and on release, to either continuation of their methadone treatment or to usual care--forced tapered withdrawal from methadone. Participants could be included in the study only if their incarceration would be more than 1 week but less than 6 months. We did the random assignments with a computer-generated random permutation, and urn randomisation procedures to stratify participants by sex and race. Participants in the continued-methadone group were maintained on their methadone dose at the time of their incarceration (with dose adjustments as clinically indicated). Patients in the forced-withdrawal group followed the institution's standard withdrawal protocol of receiving methadone for 1 week at the dose at the time of their incarceration, then a tapered withdrawal regimen (for those on a starting dose >100 mg, the dose was reduced by 5 mg per day to 100 mg, then reduced by 3 mg per day to 0 mg; for those on a starting dose >100 mg, the dose was reduced by 3 mg per day to 0 mg). The main outcomes were engagement with a methadone maintenance-treatment clinic after release from

  11. Single-arm open-label study of Durolane (NASHA nonanimal hyaluronic acid for the treatment of osteoarthritis of the thumb

    Directory of Open Access Journals (Sweden)

    Velasco E

    2017-03-01

    Full Text Available Eloisa Velasco,1 Mª Victoria Ribera,2 Joan Pi3 1Department of Orthopedic Surgery, Hospital de Sant Joan Despí Moisés Broggi, Barcelona, Spain; 2Department of Anesthesiology, Vall d’Hebron University Hospital, Barcelona, Spain; 3Department of Orthopedics and Traumatology, Parc Taulí University Hospital, Sabadell, Barcelona, Spain Introduction: Osteoarthritis of the trapeziometacarpal (TMC joint of the thumb – also known as rhizarthrosis – is painful and has a significant impact on quality of life. Intra-articular injection of hyaluronic acid may potentially meet the need for effective, minimally invasive intervention in patients not responding adequately to initial treatment. We aimed to confirm the safety and effectiveness of viscosupplementation with Durolane (NASHA nonanimal hyaluronic acid in rhizarthrosis.Patients and methods: This was a prospective, single-arm, multicenter, open-label study with a 6-month follow-up period. Eligible patients had Eaton–Littler grade II–III rhizarthrosis in one TMC joint with pain and visual analog scale (VAS pain score ≥4 (scale: 0–10. A single injection of NASHA was administered to the affected TMC joint. The primary effectiveness variable was change from baseline in VAS pain score.Results: Thirty-five patients (mean age 60.8 years; 85.7% female received NASHA and completed the study. The least-squares mean change from baseline in VAS pain score over 6 months was –2.00, a reduction of 27.8% (p<0.001. The reduction in pain exceeded 25% as early as month 1 (26.5%, and gradual improvement was observed throughout the 6-month follow-up period. Secondary effectiveness parameters included QuickDASH (shortened version of Disabilities of the Arm, Shoulder, and Hand [DASH], Kapandji thumb opposition test, radial abduction, metacarpophalangeal (MCP joint flexion, and pinch (clamp strength. Most of these measurements showed statistically significant improvements from baseline over 6 months. Five

  12. A GPU OpenCL based cross-platform Monte Carlo dose calculation engine (goMC)

    Science.gov (United States)

    Tian, Zhen; Shi, Feng; Folkerts, Michael; Qin, Nan; Jiang, Steve B.; Jia, Xun

    2015-09-01

    Monte Carlo (MC) simulation has been recognized as the most accurate dose calculation method for radiotherapy. However, the extremely long computation time impedes its clinical application. Recently, a lot of effort has been made to realize fast MC dose calculation on graphic processing units (GPUs). However, most of the GPU-based MC dose engines have been developed under NVidia’s CUDA environment. This limits the code portability to other platforms, hindering the introduction of GPU-based MC simulations to clinical practice. The objective of this paper is to develop a GPU OpenCL based cross-platform MC dose engine named goMC with coupled photon-electron simulation for external photon and electron radiotherapy in the MeV energy range. Compared to our previously developed GPU-based MC code named gDPM (Jia et al 2012 Phys. Med. Biol. 57 7783-97), goMC has two major differences. First, it was developed under the OpenCL environment for high code portability and hence could be run not only on different GPU cards but also on CPU platforms. Second, we adopted the electron transport model used in EGSnrc MC package and PENELOPE’s random hinge method in our new dose engine, instead of the dose planning method employed in gDPM. Dose distributions were calculated for a 15 MeV electron beam and a 6 MV photon beam in a homogenous water phantom, a water-bone-lung-water slab phantom and a half-slab phantom. Satisfactory agreement between the two MC dose engines goMC and gDPM was observed in all cases. The average dose differences in the regions that received a dose higher than 10% of the maximum dose were 0.48-0.53% for the electron beam cases and 0.15-0.17% for the photon beam cases. In terms of efficiency, goMC was ~4-16% slower than gDPM when running on the same NVidia TITAN card for all the cases we tested, due to both the different electron transport models and the different development environments. The code portability of our new dose engine goMC was validated by

  13. A GPU OpenCL based cross-platform Monte Carlo dose calculation engine (goMC).

    Science.gov (United States)

    Tian, Zhen; Shi, Feng; Folkerts, Michael; Qin, Nan; Jiang, Steve B; Jia, Xun

    2015-10-07

    Monte Carlo (MC) simulation has been recognized as the most accurate dose calculation method for radiotherapy. However, the extremely long computation time impedes its clinical application. Recently, a lot of effort has been made to realize fast MC dose calculation on graphic processing units (GPUs). However, most of the GPU-based MC dose engines have been developed under NVidia's CUDA environment. This limits the code portability to other platforms, hindering the introduction of GPU-based MC simulations to clinical practice. The objective of this paper is to develop a GPU OpenCL based cross-platform MC dose engine named goMC with coupled photon-electron simulation for external photon and electron radiotherapy in the MeV energy range. Compared to our previously developed GPU-based MC code named gDPM (Jia et al 2012 Phys. Med. Biol. 57 7783-97), goMC has two major differences. First, it was developed under the OpenCL environment for high code portability and hence could be run not only on different GPU cards but also on CPU platforms. Second, we adopted the electron transport model used in EGSnrc MC package and PENELOPE's random hinge method in our new dose engine, instead of the dose planning method employed in gDPM. Dose distributions were calculated for a 15 MeV electron beam and a 6 MV photon beam in a homogenous water phantom, a water-bone-lung-water slab phantom and a half-slab phantom. Satisfactory agreement between the two MC dose engines goMC and gDPM was observed in all cases. The average dose differences in the regions that received a dose higher than 10% of the maximum dose were 0.48-0.53% for the electron beam cases and 0.15-0.17% for the photon beam cases. In terms of efficiency, goMC was ~4-16% slower than gDPM when running on the same NVidia TITAN card for all the cases we tested, due to both the different electron transport models and the different development environments. The code portability of our new dose engine goMC was validated by

  14. A GPU OpenCL based cross-platform Monte Carlo dose calculation engine (goMC)

    International Nuclear Information System (INIS)

    Tian, Zhen; Shi, Feng; Folkerts, Michael; Qin, Nan; Jiang, Steve B; Jia, Xun

    2015-01-01

    Monte Carlo (MC) simulation has been recognized as the most accurate dose calculation method for radiotherapy. However, the extremely long computation time impedes its clinical application. Recently, a lot of effort has been made to realize fast MC dose calculation on graphic processing units (GPUs). However, most of the GPU-based MC dose engines have been developed under NVidia’s CUDA environment. This limits the code portability to other platforms, hindering the introduction of GPU-based MC simulations to clinical practice. The objective of this paper is to develop a GPU OpenCL based cross-platform MC dose engine named goMC with coupled photon–electron simulation for external photon and electron radiotherapy in the MeV energy range. Compared to our previously developed GPU-based MC code named gDPM (Jia et al 2012 Phys. Med. Biol. 57 7783–97), goMC has two major differences. First, it was developed under the OpenCL environment for high code portability and hence could be run not only on different GPU cards but also on CPU platforms. Second, we adopted the electron transport model used in EGSnrc MC package and PENELOPE’s random hinge method in our new dose engine, instead of the dose planning method employed in gDPM. Dose distributions were calculated for a 15 MeV electron beam and a 6 MV photon beam in a homogenous water phantom, a water-bone-lung-water slab phantom and a half-slab phantom. Satisfactory agreement between the two MC dose engines goMC and gDPM was observed in all cases. The average dose differences in the regions that received a dose higher than 10% of the maximum dose were 0.48–0.53% for the electron beam cases and 0.15–0.17% for the photon beam cases. In terms of efficiency, goMC was ∼4–16% slower than gDPM when running on the same NVidia TITAN card for all the cases we tested, due to both the different electron transport models and the different development environments. The code portability of our new dose engine goMC was

  15. Adjuvant effect of Chakshushya Rasayana with beta-blocker eye drops in the management of progressive glaucomatous optic neuropathy: An open-label randomized controlled trial.

    Science.gov (United States)

    Dhiman, K S; Adhoor, Veeranagouda S; Agarwal, Riju; Mehta, Amit J

    2016-01-01

    Primary open angle glaucoma is an insidious and chronic vision-threatening eye ailment due to neuro-retino-optic nerve degeneration, which may be due to the raised intraocular pressure (IOP) or due to independent factors. Management of glaucoma is mainly concentrated on lowering IOP that requires lifetime topical medication, different ocular medicaments for lowering of IOP, and surgical interventions, but it has its own limitations to control the progression of glaucomatous optic neuropathy (GON), and this is the reason behind the use of alternative neuroprotective adjuvants. To evaluate the neuroprotective effect of Ayurvedic line of management of progressive GON. Ingredients of trial drug Vara Fort powder ( Chakshushya Rasayana ) were procured from the Institute Pharmacy, except Swarnamakshika Bhasma , which was purchased from Dhootapapeshwar Pharmaceuticals. The patients fulfilling inclusion criteria, attending outpatient and inpatient departments, irrespective of their sex, race, religion, occupation, etc., were selected and divided into two groups with open-labeled randomization. In Group A, in addition to betaxolol (0.1%) or timolol (0.5%) (non-iobrim), Chakshushya Rasayana 6 g/day orally with Triphala Ghrita and honey along with Koshtha-Shuddhi (body-microchannel clearing treatment) protocol was tried. Nasya (oleation through nasal route) with Jeevantyadi Taila and Tarpana (eye satiation) with Go-Ghrita were also performed. In Group B (control), brimonidine (iobrim) 0.2% eye drop was used for 3 months. Significant improvement was observed in subjective parameters in Group A such as blurred vision, frequent change of presbyopic glasses, and delayed dark adaptation. Chakshushya Rasayana , if administered in a systematic approach along with a modern topical betaxolol or timolol eye drops, has a definite role in improving the lost retinal sensitivity as much as up to 12 dB in 3 months duration.

  16. Evaluation of fleroxacin (RO 23-6240) as single-oral-dose therapy of culture-proven chancroid in Nairobi, Kenya.

    Science.gov (United States)

    MacDonald, K S; Cameron, D W; D'Costa, L; Ndinya-Achola, J O; Plummer, F A; Ronald, A R

    1989-01-01

    Chancroid is gaining importance as a sexually transmitted disease because of its association with transmission of human immunodeficiency virus type 1 (HIV-1). Effective, simply administered therapy for chancroid is necessary. Fleroxacin is effective against Haemophilus ducreyi in vitro. We performed an initial randomized clinical trial to assess the efficacy of fleroxacin for treatment of chancroid in Nairobi, Kenya. Fifty-three men with culture-positive chancroid were randomly assigned to receive either 200 mg (group 1) or 400 mg (group 2) of fleroxacin as a single oral dose. Groups 1 and 2 were similar with regard to severity of disease, bubo formation, and HIV-1 status. A satisfactory clinical response to therapy was noted in 23 of 26 patients (88%) in group 1 and 18 of 23 patients (78%) in group 2. Bacteriological failure occurred in 1 of 26 evaluable patients (4%) in group 1 and 4 of 23 evaluable patients (17%) in group 2. Two of 37 HIV-1-seronegative men (5%) and 3 of 11 HIV-1-infected men (27%) were bacteriological failures. Fleroxacin, 200 or 400 mg as a single oral dose, is efficacious therapy for microbiologically proven chancroid in patients who do not have concurrent HIV-1 infection. Among HIV-1-infected men, a single dose of 200 or 400 mg of fleroxacin is inadequate therapy for chancroid. PMID:2502065

  17. [{sup 131}I]FIAU labeling of genetically transduced, tumor-reactive lymphocytes: cell-level dosimetry and dose-dependent toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Zanzonico, Pat [Memorial Sloan-Kettering Cancer Center, Department of Medical Physics, New York, NY (United States); Koehne, Guenther; Doubrovina, Ekaterina; O' Reilly, Richard J. [Memorial Sloan-Kettering Cancer Center, Allogeneic Transplantation Service, New York, NY (United States); Memorial Sloan-Kettering Cancer Center, Immunology Program, New York, NY (United States); Gallardo, Humilidad F. [Memorial Sloan-Kettering Cancer Center, Gene Transfer and Somatic Cell Engineering Facility, New York, NY (United States); Doubrovin, Mikhail; Blasberg, Ronald G. [Memorial Sloan-Kettering Cancer Center, Department of Radiology, New York, NY (United States); Memorial Sloan-Kettering Cancer Center, Department of Neurology, New York, NY (United States); Finn, Ronald [Memorial Sloan-Kettering Cancer Center, Radiochemistry and Cyclotron Core Facility, New York, NY (United States); Riviere, Isabelle; Sadelain, Michel [Memorial Sloan-Kettering Cancer Center, Immunology Program, New York, NY (United States); Memorial Sloan-Kettering Cancer Center, Gene Transfer and Somatic Cell Engineering Facility, New York, NY (United States); Larson, Steven M. [Memorial Sloan-Kettering Cancer Center, Department of Radiology, New York, NY (United States)

    2006-09-15

    Donor T cells have been shown to be reactive against and effective in adoptive immunotherapy of Epstein-Barr virus (EBV) lymphomas which develop in some leukemia patients post marrow transplantation. These T cells may be genetically modified by incorporation of a replication-incompetent viral vector (NIT) encoding both an inactive mutant nerve growth factor receptor (LNGFR), as an immunoselectable surface marker, and a herpes simplex virus thymidine kinase (HSV-TK), rendering the cells sensitive to ganciclovir. The current studies are based on the selective HSV-TK-catalyzed trapping (phosphorylation) of the thymidine analog [{sup 131}I]-2'-fluoro-2'-deoxy-1-{beta}-D-arabinofuransyl-5-iodo-uracil (FIAU) as a means of stably labeling such T cells for in vivo trafficking (including tumor targeting) studies. Because of the radiosensitivity of lymphocytes and the potentially high absorbed dose to the nucleus from intracellular {sup 131}I (even at tracer levels), the nucleus absorbed dose (D{sub n}) and dose-dependent immune functionality were evaluated for NIT {sup +} T cells labeled ex vivo in [{sup 131}I ]FIAU-containing medium. Based on in vitro kinetic studies of [{sup 131}I ]FIAU uptake by NIT {sup +} T cells, D{sub n} was calculated using an adaptation of the MIRD formalism and the recently published MIRD cellular S factors. Immune cytotoxicity of [{sup 131}I ]FIAU-labeled cells was assayed against {sup 51}Cr-labeled target cells [B-lymphoblastoid cells (BLCLs) ] in a standard 4-h release assay. At median nuclear absorbed doses up to 830 cGy, a {sup 51}Cr-release assay against BLCLs showed no loss of immune cytotoxicity, thus demonstrating the functional integrity of genetically transduced, tumor-reactive T cells labeled at this dose level for in vivo cell trafficking and tumor targeting studies. (orig.)

  18. Effectiveness of a single application of 0·25% fipronil solution for the treatment of hirstiellosis in captive green iguanas (Iguana iguana): an open-label study.

    Science.gov (United States)

    Farmaki, Rania; Simou, Chrisa; Papadopoulos, Elias; Koutinas, Alexander F; Saridomichelakis, Manolis N

    2013-08-01

    Hirstiella spp. are common ectoparasites of captive green iguanas (Iguana iguana). Suggested treatments are empirical and some of them are of low efficacy and potentially toxic. The objective of this open-label study was to investigate the short-term efficacy and safety of a single application of 0·25% fipronil solution for the treatment of hirstiellosis. The skin of 50 green iguanas was thoroughly examined with the aid of bright light and magnifying lenses. A total of 21 iguanas were found to be infested, harbouring 1-24 mites (median: 5). All 35 mites collected from 17 iguanas were identified as Hirstiella sp. Both infested and non-infested lizards, sharing the same enclosure, were carefully wiped with 0·25% fipronil solution. The safety and the efficacy of the treatment were evaluated after 2 days in 47/50 (94%) and 7 days in 29/50 (58%) iguanas. Compared with pre-treatment levels, the parasitic load did not changed significantly on the second day but was significantly lower on day 7 (P = 0·006). No adverse reactions were noticed. Based on these results a single whole-body application of 0·25% fipronil solution can be considered a safe and effective treatment for the reduction of parasitic burden in captive green iguanas infested by Hirstiella sp. mites.

  19. The dose dependency of the over-dispersion of quartz OSL single grain dose distributions

    DEFF Research Database (Denmark)

    Thomsen, Kristina Jørkov; Murray, Andrew S.; Jain, Mayank

    2012-01-01

    The use of single grain quartz OSL dating has become widespread over the past decade, particularly with application to samples likely to have been incompletely bleached before burial. By reducing the aliquot size to a single grain the probability of identifying the grain population most likely...... to have been well-bleached at deposition is maximised and thus the accuracy with which the equivalent dose can be determined is – at least in principle – improved. However, analysis of single grain dose distributions requires knowledge of the dispersion of the well-bleached part of the dose distribution....... This can be estimated by measurement of a suitable analogue, e.g. a well-bleached aeolian sample, but this requires such an analogue to be available, and in addition the assumptions that the sample is in fact a) well-bleached, and b) has a similar dose rate heterogeneity to the fossil deposit. Finally...

  20. Mobility and height detection of particle labels in an optical evanescent wave biosensor with single-label resolution

    Energy Technology Data Exchange (ETDEWEB)

    Van Ommering, Kim; Koets, Marjo; Schleipen, Jean J H B; Prins, Menno W J [Philips Research Laboratories, 5656 AE Eindhoven (Netherlands); Somers, Philip A; Van IJzendoorn, Leo J, E-mail: menno.prins@philips.co [Department of Applied Physics, Eindhoven University of Technology, 5600 MB Eindhoven (Netherlands)

    2010-04-21

    Particle labels are used in biosensors to detect the presence and concentration of analyte molecules. In this paper we demonstrate an optical technique to measure the mobility and height of bound particle labels on a biosensor surface with single-label resolution. The technique is based on the detection of the particle-induced light scattering in an optical evanescent field. We show that the thermal particle motion in the optical evanescent field leads to intensity fluctuations that can accurately be detected. The technique is demonstrated using 290 bp (99 nm) DNA as an analyte and using polystyrene particles and magnetic particles with diameters between 500 and 1000 nm as labels. The particle intensity histograms show that quantitative height measurements are obtained for particles with uniform optical properties, and the intensity versus position plots reflect the analyte-antibody orientation and the analyte flexibility. The novel optical detection technique will lead to biosensors with very high sensitivity and specificity.

  1. Impact of Different Front-of-Pack Nutrition Labels on Consumer Purchasing Intentions: A Randomized Controlled Trial.

    Science.gov (United States)

    Ducrot, Pauline; Julia, Chantal; Méjean, Caroline; Kesse-Guyot, Emmanuelle; Touvier, Mathilde; Fezeu, Léopold K; Hercberg, Serge; Péneau, Sandrine

    2016-05-01

    Despite growing evidence supporting the utility of front-of-pack nutrition labels in enabling consumer evaluation of food product healthiness, research on food choices is scarce. This study aims at comparing the impact of front-of-pack nutrition labels on consumers' purchasing intentions. Five-arm, open-label RCT. The study setting was a virtual web-based supermarket, with participants from the French NutriNet-Santé study. The eligibility requirement was grocery shopping involvement. The intervention was to simulate one shopping situation with front-of-pack nutrition labels affixed on food products (December 2014 to March 2015). Participants were randomly assigned to one of five exposure conditions using a central computer system: Guideline Daily Amounts, Multiple Traffic Lights, Five-Color Nutrition Label, Green Tick, or control (no front-of-pack exposure). Given the nature of the intervention, masking of participants was not performed. The primary outcome was the overall nutritional quality of the contents of the shopping cart, estimated using the United Kingdom Food Standards Agency nutrient profiling system. Secondary outcomes included energy and nutrient content of the shopping cart. Impact of the front-of-pack labels was also evaluated across sociodemographic subgroups based on age, educational level, income, and nutrition knowledge. A total of 11,981 participants were included in the analyses (April 2015). The Five-Color Nutrition Label significantly led to the highest overall nutritional quality of the shopping cart, as reflected by lower Food Standards Agency scores (M=8.72; SD=2.75), followed by Multiple Traffic Lights (M=8.97; SD=2.68) and Green Tick (M=8.99; SD=2.71), compared with the control (M=9.34; SD=2.57) (p<0.0001). The Five-Color Nutrition Label was the only front-of-pack format that led to a lower content in lipids, saturated fatty acids, and sodium of the shopping cart (all p<0.05). The impact of the different front-of-pack labels was similar

  2. Effect of a single intraoperative high-dose ATG-Fresenius on delayed graft function in donation after cardiac-death donor renal allograft recipients: a randomized study.

    Science.gov (United States)

    van den Hoogen, Martijn W F; Kho, Marcia M L; Abrahams, Alferso C; van Zuilen, Arjan D; Sanders, Jan-Stephan; van Dijk, Marja; Hilbrands, Luuk B; Weimar, Willem; Hoitsma, Andries J

    2013-04-01

    Reducing the incidence of delayed graft function after transplant with donation after cardiac death donor renal allografts would facilitate managing recipients during their first weeks after a transplant. To reduce this incidence, in most studies, induction therapy with depleting anti-T-lymphocyte antibodies is coupled with a reduction of the dosage of the calcineurin inhibitor. The separate effect of anti-T-cell therapy on the incidence and duration of delayed graft function is therefore difficult to assess. We performed a randomized study to evaluate the effect of a single intraoperative high-dose of anti-T-lymphocyte immunoglobulin (ATG)-Fresenius (9 mg/kg body weight) on the incidence of delayed graft function. Eligible adult recipients of a first donation after cardiac death donor renal allograft were randomly assigned to ATG-Fresenius or no induction therapy. Maintenance immunosuppression consisted of tacrolimus, in an unadjusted dose, mycophenolate mofetil, and steroids. The study was prematurely terminated because of a lower-than-anticipated inclusion rate. Baseline characteristics were comparable in the ATG-Fresenius group (n=28) and the control group (n=24). Twenty-two patients in the ATG-Fresenius group (79%) had delayed graft function, compared with 13 in the control group (54%; P = .06). Allograft and patient survival were comparable in both groups. Serious adverse events occurred more frequently in the ATG-Fresenius group than they did in the control group (57% vs 29%; P Fresenius in donation after cardiac death donor renal allograft recipients, followed by triple immunosuppression with an unadjusted tacrolimus dose, seems ineffective to reduce the incidence of delayed graft function. Moreover, this was associated with a higher rate of serious adverse events (EudraCT-number, 2007-000210-36.).

  3. Duloxetine in the long-term management of diabetic peripheral neuropathic pain: An open-label, 52-week extension of a randomized controlled clinical trial.

    Science.gov (United States)

    Wernicke, Joachim F; Raskin, Joel; Rosen, Amy; Pritchett, Yili L; D'Souza, Deborah N; Iyengar, Smriti; Knopp, Kelly; Le, Trong K

    2006-09-01

    Duloxetine hydrochloride, a selective serotonin (5-HT) and norepinephrine (NE) reuptake inhibitor, is relatively balanced in its affinity for both 5-HT and NE reuptake inhibition and is the first US Food and Drug Administration-approved prescription drug for the management of diabetic peripheral neuropathic pain (DPNP). The aim of this study was to determine whether management of DPNP with duloxetine interferes with the treatment of diabetes. It also examined the tolerability of long-term exposure to duloxetine with regard to the progression of diabetic complications, and assessed the impact of DPNP management with duloxetine versus routine care. This was a 52-week, multicenter, re-randomized, open-label extension of a parallel, double-blind, randomized, placebo-controlled, acute (12-week) study. Patients who completed the duloxetine or placebo acute treatment period were randomly reassigned in a 2:1 ratio to treatment with duloxetine 60 mg BID or routine care for an additional 52 weeks. The study included male and female outpatients aged ≥18 years with a diagnosis of DPNP caused by type 1 or type 2 diabetes. Over the course of the 52-week study, visits were scheduled on the following weeks (of the extension phase of the study): 1 (via phone only), 2, 4, 8, 12, 20, 28, 40, and 52. Tolerability was assessed by review and analyses of discontinuation rates, adverse events (AEs), laboratory data, vital signs, electrocardiographic results, concomitant medications, and diabetic complications. Treatment-emergent AEs (TEAEs) were defined as AEs that appeared during therapy (were not present at baseline) or were exacerbated during treatment. Data on AEs and concomitant medications were collected at every visit. Data on blood pressure, heart rate, and significant hypoglycemic events were collected at every visit starting from week 2. Fasting clinical chemistry and electrolyte group laboratory assessments were done at every visit, starting from week 4. Electrocardiographic

  4. Switching to aripiprazole in outpatients with schizophrenia experiencing insufficient efficacy and/or safety/tolerability issues with risperidone: a randomized, multicentre, open-label study.

    Science.gov (United States)

    Ryckmans, V; Kahn, J P; Modell, S; Werner, C; McQuade, R D; Kerselaers, W; Lissens, J; Sanchez, R

    2009-05-01

    This study evaluated the safety/tolerability and effectiveness of aripiprazole titrated-dose versus fixed-dose switching strategies from risperidone in patients with schizophrenia experiencing insufficient efficacy and/or safety/tolerability issues. Patients were randomized to an aripiprazole titrated-dose (starting dose 5 mg/day) or fixed-dose (dose 15 mg/day) switching strategy with risperidone down-tapering. Primary endpoint was rate of discontinuation due to adverse events (AEs) during the 12-week study. Secondary endpoints included positive and negative syndrome scale (PANSS), clinical global impressions - improvement of illness scale (CGI-I), preference of medication (POM), subjective well-being under neuroleptics (SWN-K) and GEOPTE (Grupo Español para la Optimización del Tratamiento de la Esquizofrenia) scales. Rates of discontinuations due to AEs were similar between titrated-dose and fixed-dose strategies (3.5% vs. 5.0%; p=0.448). Improvements in mean PANSS total scores were similar between aripiprazole titrated-dose and fixed-dose strategies (-14.8 vs. -17.2; LOCF), as were mean CGI-I scores (2.9 vs. 2.8; p=0.425; LOCF) and SWN-K scores (+8.6 vs.+10.3; OC,+7.8 vs.+9.8; LOCF). Switching can be effectively and safely achieved through a titrated-dose or fixed-dose switching strategy for aripiprazole, with down-titration of risperidone.

  5. Off-label biologic regimens in psoriasis: a systematic review of efficacy and safety of dose escalation, reduction, and interrupted biologic therapy.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Brezinski

    Full Text Available OBJECTIVES: While off-label dosing of biologic treatments may be necessary in selected psoriasis patients, no systematic review exists to date that synthesizes the efficacy and safety of these off-label dosing regimens. The aim of this systematic review is to evaluate efficacy and safety of off-label dosing regimens (dose escalation, dose reduction, and interrupted treatment with etanercept, adalimumab, infliximab, ustekinumab, and alefacept for psoriasis treatment. DATA SOURCES AND STUDY SELECTION: We searched OVID Medline from January 1, 1990 through August 1, 2011 for prospective clinical trials that studied biologic therapy for psoriasis treatment in adults. Individual articles were screened for studies that examined escalated, reduced, or interrupted therapy with etanercept, adalimumab, infliximab, ustekinumab, or alefacept. DATA SYNTHESIS: A total of 23 articles with 12,617 patients matched the inclusion and exclusion criteria for the systematic review. Data were examined for primary and secondary efficacy outcomes and adverse events including infections, malignancies, cardiovascular events, and anti-drug antibodies. The preponderance of data suggests that continuous treatment with anti-TNF agents and anti-IL12/23 agent was necessary for maintenance of disease control. Among non-responders, dose escalation with etanercept, adalimumab, ustekinumab, and alefacept typically resulted in greater efficacy than standard dosing. Dose reduction with etanercept and alefacept resulted in reduced efficacy. Withdrawal of the examined biologics led to an increase in disease activity; efficacy from retreatment did not result in equivalent initial response rates for most biologics. Safety data on off-label dosing regimens are limited. CONCLUSION: Dose escalation in non-responders generally resulted in increased efficacy in the examined biologics used to treat moderate-to-severe psoriasis. Continuous treatment with anti-TNF agents and anti-IL12/23 agent

  6. Study on relations between heavy ions single event upset cross sections and γ accumulated doses

    International Nuclear Information System (INIS)

    He Chaohui; Geng Bin; Wang Yanping; Peng Honglun; Yang Hailiang; Chen Xiaohua; Li Guozheng

    2002-01-01

    Experiments were done under 252 Cf and 60 Co γ source to study the relation between heavy ion Single Event Upset (SEU) cross sections and γ accumulated doses. There was no obvious rule and little influence of γ accumulated doses on SEU cross sections when Static Random Access Memories were in power off mode and static power on mode. In active measuring mode, the SEU cross section increased as the accumulated doses increasing when same data were written in memory cells. If reverse data, such as '55' and 'AA', were written in memory cells during the experiment, the SEU cross sections decreased to the level when memories were not irradiated under 60 Co γ source, even more small. It implied that the influence of γ accumulated doses on SEU cross sections can be set off by this method

  7. Device-independent randomness amplification with a single device

    International Nuclear Information System (INIS)

    Plesch, Martin; Pivoluska, Matej

    2014-01-01

    Expansion and amplification of weak randomness with untrusted quantum devices has recently become a very fruitful topic of research. Here we contribute with a procedure for amplifying a single weak random source using tri-partite GHZ-type entangled states. If the quality of the source reaches a fixed threshold R=log 2 ⁡(10), perfect random bits can be produced. This technique can be used to extract randomness from sources that can't be extracted neither classically, nor by existing procedures developed for Santha–Vazirani sources. Our protocol works with a single fault-free device decomposable into three non-communicating parts, that is repeatedly reused throughout the amplification process. - Highlights: • We propose a protocol for device independent randomness amplification. • Our protocol repeatedly re-uses a single device decomposable into three parts. • Weak random sources with min-entropy rate greater than 1/4 log 2 ⁡(10) can be amplified. • Security against all-quantum adversaries is achieved

  8. Monovalent type-1 oral poliovirus vaccine given at short intervals in Pakistan: a randomised controlled, four-arm, open-label, non-inferiority trial.

    Science.gov (United States)

    Mir, Fatima; Quadri, Farheen; Mach, Ondrej; Ahmed, Imran; Bhatti, Zaid; Khan, Asia; Rehman, Najeeb Ur; Durry, Elias; Salama, Maha; Oberste, Steven M; Weldon, William C; Sutter, Roland W; Zaidi, Anita K M

    2015-08-01

    Supplementary immunisation activities with oral poliovirus vaccines (OPVs) are usually separated by 4 week intervals; however, shorter intervals have been used in security-compromised areas and for rapid outbreak responses. We assessed the immunogenicity of monovalent type-1 oral poliovirus vaccine (mOPV1) given at shorter than usual intervals in Karachi, Pakistan. This was a multicentre, randomised, controlled, four-arm, open-label, non-inferiority trial done at five primary health-care centres in low-income communities in and around Karachi, Pakistan. Eligible participants were healthy newborn babies with a birthweight of at least 2·5 kg, for whom informed consent was provided by their parent or guardian, and lived less than 30 km from the study clinic. After receiving a birth dose of trivalent OPV, we enrolled and randomly assigned newborn babies (1:1:1:1) to receive two doses of mOPV1 with an interval of 1 week (mOPV1-1 week), 2 weeks (mOPV1-2 weeks), or 4 weeks (mOPV1-4 weeks) between doses, or two doses of bivalent OPV (bOPV) with an interval of 4 weeks between doses (bOPV-4 weeks). We gave the first study dose of OPV at age 6 weeks. We did the randomisation with a centrally generated, computerised allocation sequence with blocks of 16; participants' families and study physicians could not feasibly be masked to the allocations. Trial participants were excluded from local supplementary immunisation activities during the study period. The primary outcome was non-inferiority (within a 20% margin) between groups in seroconversion to type-1 poliovirus. The primary and safety analyses were done in the per-protocol population of infants who received all three doses of vaccine. This trial is registered with ClinicalTrials.gov, number NCT01586572, and is closed to new participants. Between March 1, 2012, and May 31, 2013, we enrolled 1009 newborn babies, and randomly assigned 829 (82%) to treatment. 554 (67%) of the 829 babies were included in the per

  9. Comparison of toxin removal outcomes in online hemodiafiltration and intra-dialytic exercise in high-flux hemodialysis: A prospective randomized open-label clinical study protocol

    Directory of Open Access Journals (Sweden)

    Maheshwari Vaibhav

    2012-11-01

    Full Text Available Abstract Background Maintenance hemodialysis (HD patients universally suffer from excess toxin load. Hemodiafiltration (HDF has shown its potential in better removal of small as well as large sized toxins, but its efficacy is restricted by inter-compartmental clearance. Intra-dialytic exercise on the other hand is also found to be effective for removal of toxins; the augmented removal is apparently obtained by better perfusion of skeletal muscles and decreased inter-compartmental resistance. The aim of this trial is to compare the toxin removal outcome associated with intra-dialytic exercise in HD and with post-dilution HDF. Methods/design The main hypothesis of this study is that intra-dialytic exercise enhances toxin removal by decreasing the inter-compartmental resistance, a major impediment for toxin removal. To compare the HDF and HD with exercise, the toxin rebound for urea, creatinine, phosphate, and β2-microglobulin will be calculated after 2 hours of dialysis. Spent dialysate will also be collected to calculate the removed toxin mass. To quantify the decrease in inter-compartmental resistance, the recently developed regional blood flow model will be employed. The study will be single center, randomized, self-control, open-label prospective clinical research where 15 study subjects will undergo three dialysis protocols (a high flux HD, (b post-dilution HDF, (c high flux HD with exercise. Multiple blood samples during each study session will be collected to estimate the unknown model parameters. Discussion This will be the first study to investigate the exercise induced physiological change(s responsible for enhanced toxin removal, and compare the toxin removal outcome both for small and middle sized toxins in HD with exercise and HDF. Successful completion of this clinical research will give important insights into exercise effect on factors responsible for enhanced toxin removal. The knowledge will give confidence for implementing

  10. Effect of a Single Dose of Dextromethorphan on Psychomotor Performance and Working Memory Capacity

    OpenAIRE

    Al-Kuraishy, Hayder M.; Al-Gareeb, Ali I.; Ashor, Ammar Waham

    2012-01-01

    Background: Previous studies show that the prolonged use of dextromethorphan produces cognitive deterioration in humans. Aim: The aim of this study was to investigate the effect of a single dose of dextroemthrophan on psychomotor performance and working memory capacity. Materials and Methods: This is a randomized, double-blind, controlled, and prospective study. Thirty-six (17 women, 19 men) medical students enrolled in the study; half of them (7 women, 11 men) were given placebo, while the o...

  11. Effect of a single dose of dextromethorphan on psychomotor performance and working memory capacity.

    Science.gov (United States)

    Al-Kuraishy, Hayder M; Al-Gareeb, Ali I; Ashor, Ammar Waham

    2012-04-01

    Previous studies show that the prolonged use of dextromethorphan produces cognitive deterioration in humans. The aim of this study was to investigate the effect of a single dose of dextroemthrophan on psychomotor performance and working memory capacity. This is a randomized, double-blind, controlled, and prospective study. Thirty-six (17 women, 19 men) medical students enrolled in the study; half of them (7 women, 11 men) were given placebo, while the other half (10 women, 8 men) received dextromethorphan. The choice reaction time, critical flicker fusion threshold, and N-back working memory task were measured before and after 2 h of taking the drugs. Dextromethorphan showed a significant deterioration in the 3-back working memory task (P0.05). On the other hand, placebo showed no significant changes as regards the choice reaction time, critical flicker fusion threshold, and N-back working memory task (P>0.05). A single dose of dextromethorphan has no effect on attention and arousal but may significantly impair the working memory capacity.

  12. The effect of food on the pharmacokinetics of oral ibrutinib in healthy participants and patients with chronic lymphocytic leukemia.

    Science.gov (United States)

    de Jong, Jan; Sukbuntherng, Juthamas; Skee, Donna; Murphy, Joe; O'Brien, Susan; Byrd, John C; James, Danelle; Hellemans, Peter; Loury, David J; Jiao, Juhui; Chauhan, Vijay; Mannaert, Erik

    2015-05-01

    To assess ibrutinib pharmacokinetics under fasted and fed conditions, impact of food-intake timing, and the safety and tolerability. Three studies were analyzed. Study 1 was a randomized, open-label, single-dose, four-way crossover study in 44 healthy participants. Study 2 was a randomized, repeat-dose crossover study in 16 patients with previously treated chronic lymphocytic leukemia (CLL). Ibrutinib dose was 420 mg in both studies. Study 3 was an open-label, sequential study to assess the effect of a standard breakfast on ibrutinib 560 mg in eight healthy participants. Administration of single-dose ibrutinib under fasting conditions (study 1) resulted in approximately 60 % of exposure compared with drug intake either 30 min before, 30 min after (fed), or 2 h after a high-fat meal. Similar food effect was observed (study 3) when ibrutinib was given 30 min before meal. In CLL patients (study 2), the C max and AUC under fasting conditions were 43 and 61 %, respectively, relative to fed conditions. When administered once-daily in uncontrolled food-intake conditions (≥30 min before or 2 h after), exposures were slightly (≈30 %) lower than in fed condition. When corrected for repeated dosing, pharmacokinetic parameters in healthy participants and patients were comparable. Ibrutinib was generally well tolerated in all settings studied. Ibrutinib administered in fasted condition reduces exposure to approximately 60 % as compared with dosing in proximity to food-intake, regardless of timing/type of meal. Because repeated drug intake in fasted condition is unlikely, no food restrictions may be needed to administer ibrutinib.

  13. Actual use of and adherence to ibuprofen 400 mg tablet dosing instructions in a simulated OTC environment
.

    Science.gov (United States)

    Meeves, Suzanne; Leyva, Rina; Richardson, Clark; Wilson, Brenda; Savastano, David M

    2017-07-01

    Evaluate adherence of US consumers to proposed label directions for a new 400 mg ibuprofen formulation. In this single-arm, open-label, multicenter, 30-day study simulating an over-the-counter (OTC)-like environment, US analgesic consumers reviewed proposed product packaging for a new 400 mg ibuprofen formulation and made a purchase decision. Purchasers used the product as needed and recorded use over 30 days. Outcomes included the percentage of participants who exhibited correct or acceptable product use for the primary endpoint (not exceeding 1,200 mg/day > 2 times during the study) or secondary endpoint (not exceeding 400 mg/dose > 2 times during the study) and adherence to the labeled dosing interval of 6 - 8 hours. Primary endpoint success was met if the lower bound of the 95% confidence interval (CI) was ≥ 85%. Of 685 purchasers providing use data, correct or acceptable use behavior occurred in 95.2% (95% CI: 93.6%, 96.8%) regarding total daily dose and in 84.4% (95% CI: 81.7%, 87.1%) regarding the number of tablets taken per dosing occasion. Most participants (87.3%) never used > 1,200 mg/day or took > 1 tablet/dose (78.1%). Nearly 43% of subjects re-dosed within 6 hours of the previous dose; of these, ~ 82% re-dosed between the 4- and 6-hour time intervals. Adverse events were consistent with prior ibuprofen 200 mg experience. This study provides evidence that a majority of US consumers would be able to use OTC ibuprofen 400 mg tablets in a manner consistent with product labeling. Misuse rates were low and unlikely to generate an excess risk of clinically important adverse events.
.

  14. Estimation of organ cumulated activities and absorbed doses on intakes of several 11C labelled radiopharmaceuticals from external measurement with thermoluminescent dosimeters.

    Science.gov (United States)

    Nakamura, T; Hayashi, Y; Watabe, H; Matsumoto, M; Horikawa, T; Fujiwara, T; Ito, M; Yanai, K

    1998-02-01

    We have developed a method for obtaining the cumulated activities in organs from radionuclides, which are injected into the patient in nuclear medicine procedures, by external exposure measurement with thermoluminescent dosimeters (TLDs) which are attached to the patient's body surface close to source organs to obtain information on body-surface doses. As the surface dose is connected to the cumulated activities in source organs through radiation transmission in the human body which can be estimated with the aid of a mathematical phantom, the organ cumulated activities can be obtained by the inverse transform method. The accuracy of this method was investigated by using a water phantom in which several gamma-ray volume sources of known activity were placed to simulate source organs. We then estimated by external measurements the organ cumulated activities and absorbed doses in subjects to whom the radiopharmaceuticals 11C-labelled Doxepin, 11C-labelled YM09151-2 and 11C-labelled Benzotropin were administered in clinical nuclear medicine procedures. The cumulated activities in the brain obtained with TLDs for Doxepin and YM09151-2 are 63.6 +/- 6.2 and 32.1 +/- 12.0 kBq h MBq-1 respectively, which are compared with the respective values of 33.3 +/- 9.9 and 23.9 +/- 6.2 kBq h MBq-1 with direct PET (positron emission tomography) measurements. The agreement between the two methods is within a factor of two. The effective doses of Doxepin, YM09151-2 and Benzotropin are determined as 6.92 x 10(-3), 7.08 x 10(-3) and 7.65 x 10(-3) mSv MBq-1 respectively with the TLD method. This method has great advantages, in that cumulated activities in several organs can be obtained easily with a single procedure, and the measurements of body surface doses are performed simultaneously with the nuclear medicine procedure, as TLDs are too small to interfere with other medical measurements.

  15. Effect of mirtazapine versus selective serotonin reuptake inhibitors on benzodiazepine use in patients with major depressive disorder: a pragmatic, multicenter, open-label, randomized, active-controlled, 24-week trial.

    Science.gov (United States)

    Hashimoto, Tasuku; Shiina, Akihiro; Hasegawa, Tadashi; Kimura, Hiroshi; Oda, Yasunori; Niitsu, Tomihisa; Ishikawa, Masatomo; Tachibana, Masumi; Muneoka, Katsumasa; Matsuki, Satoshi; Nakazato, Michiko; Iyo, Masaomi

    2016-01-01

    This study aimed to evaluate whether selecting mirtazapine as the first choice for current depressive episode instead of selective serotonin reuptake inhibitors (SSRIs) reduces benzodiazepine use in patients with major depressive disorder (MDD). We concurrently examined the relationship between clinical responses and serum mature brain-derived neurotrophic factor (BDNF) and its precursor, proBDNF. We conducted an open-label randomized trial in routine psychiatric practice settings. Seventy-seven MDD outpatients were randomly assigned to the mirtazapine or predetermined SSRIs groups, and investigators arbitrarily selected sertraline or paroxetine. The primary outcome was the proportion of benzodiazepine users at weeks 6, 12, and 24 between the groups. We defined patients showing a ≥50 % reduction in Hamilton depression rating scale (HDRS) scores from baseline as responders. Blood samples were collected at baseline, weeks 6, 12, and 24. Sixty-five patients prescribed benzodiazepines from prescription day 1 were analyzed for the primary outcome. The percentage of benzodiazepine users was significantly lower in the mirtazapine than in the SSRIs group at weeks 6, 12, and 24 (21.4 vs. 81.8 %; 11.1 vs. 85.7 %, both P  depressive episodes may reduce benzodiazepine use in patients with MDD. Trial registration UMIN000004144. Registered 2nd September 2010. The date of enrolment of the first participant to the trial was 24th August 2010. This study was retrospectively registered 9 days after the first participant was enrolled.

  16. Spiromax, a New Dry Powder Inhaler: Dose Consistency under Simulated Real-World Conditions.

    Science.gov (United States)

    Canonica, Giorgio Walter; Arp, Jan; Keegstra, Johan René; Chrystyn, Henry

    2015-10-01

    Spiromax(®) is a novel dry powder inhaler for patients with asthma or chronic obstructive pulmonary disease (COPD). The studies presented here provide further data on attributes (in vitro dosing consistency with budesonide-formoterol (DuoResp) Spiromax; flow rates through empty versions of the Spiromax and Turbuhaler inhaler) of importance to patients with asthma or COPD. Dose-delivery studies were performed using low-, middle-, and high-strength DuoResp Spiromax. Dose consistency was assessed over inhaler life. Total emitted doses (TEDs) were measured at various flow rates, after exposure to high and low temperature or humidity, at different inhaler orientations, and after dropping the inhaler. The criterion for evaluating dose uniformity was whether mean TEDs were within the product specification limits. In separate studies, flow rates were measured after training, using the patient information leaflets, and again after enhanced training as part of a randomized, open-label, cross-over study. Mean values for both budesonide and formoterol were within 85%-115% of the label claim for each strength of DuoResp Spiromax for initial dose uniformity and for the other investigated conditions (temperature, humidity, orientation, dropping, knocking), with the exception of approximately an 80% increase in first dose after dropping the inhaler (subsequent doses not affected). In the flow rate patient study, two patients' inhalations with Spiromax and six with Turbuhaler were 60 L/min. DuoResp Spiromax consistently meets dose uniformity criteria, under controlled laboratory conditions and with variations intended to mimic real-world use. Following enhanced training, all patients in the flow study were able to achieve the minimal inspiratory flow rate of >30 L/min, which is required for effective treatment.

  17. Single and 30 fraction tumor control doses correlate in xenografted tumor models: implications for predictive assays

    International Nuclear Information System (INIS)

    Gerweck, Leo E.; Dubois, Willum; Baumann, Michael; Suit, Herman D.

    1995-01-01

    Purpose/Objective: In a previous publication we reported that laboratory assays of tumor clonogen number, in combination with intrinsic radiosensitivity measured in-vitro, accurately predicted the rank-order of single fraction 50% tumor control doses, in six rodent and xenografted human tumors. In these studies, tumor hypoxia influenced the absolute value of the tumor control doses across tumor types, but not their rank-order. In the present study we hypothesize that determinants of the single fraction tumor control dose, may also strongly influence the fractionaled tumor control doses, and that knowledge of tumor clonogen number and their sensitivity to fractionated irradiation, may be useful for predicting the relative sensitivity of tumors treated by conventional fractionated irradiation. Methods/Materials: Five tumors of human origin were used for these studies. Special care was taken to ensure that all tumor control dose assays were performed over the same time frame, i.e., in-vitro cells of a similar passage were used to initiate tumor sources which were expanded and used in the 3rd or 4th generation. Thirty fraction tumor control doses were performed in air breathing mice, under normal blood flow conditions (two fractions/day). The results of these studies have been previously published. For studies under uniformly (clamp) hypoxic conditions, tumors arising from the same transplantation were randomized into single or fractionated dose protocols. For estimation of the fractionated TCD50 under hypoxic conditions, tumors were exposed to six 5.4 Gy fractions (∼ 2 Gy equivalent under air), followed by graded 'top-up' dose irradiation for determination of the TCD50; the time interval between doses was 6-9 hours. The single dose equivalent of the six 5.4 Gy doses was used to calculate an extrapolated 30 fraction hypoxic TCD50. Results: Fractionation substantially increased the dose required for tumor control in 4 of the 5 tumors investigated. For these 4 tumors

  18. Effect of Genotype-Guided Warfarin Dosing on Clinical Events and Anticoagulation Control Among Patients Undergoing Hip or Knee Arthroplasty: The GIFT Randomized Clinical Trial.

    Science.gov (United States)

    Gage, Brian F; Bass, Anne R; Lin, Hannah; Woller, Scott C; Stevens, Scott M; Al-Hammadi, Noor; Li, Juan; Rodríguez, Tomás; Miller, J Philip; McMillin, Gwendolyn A; Pendleton, Robert C; Jaffer, Amir K; King, Cristi R; Whipple, Brandi DeVore; Porche-Sorbet, Rhonda; Napoli, Lynnae; Merritt, Kerri; Thompson, Anna M; Hyun, Gina; Anderson, Jeffrey L; Hollomon, Wesley; Barrack, Robert L; Nunley, Ryan M; Moskowitz, Gerard; Dávila-Román, Victor; Eby, Charles S

    2017-09-26

    Warfarin use accounts for more medication-related emergency department visits among older patients than any other drug. Whether genotype-guided warfarin dosing can prevent these adverse events is unknown. To determine whether genotype-guided dosing improves the safety of warfarin initiation. The randomized clinical Genetic Informatics Trial (GIFT) of Warfarin to Prevent Deep Vein Thrombosis included patients aged 65 years or older initiating warfarin for elective hip or knee arthroplasty and was conducted at 6 US medical centers. Enrollment began in April 2011 and follow-up concluded in October 2016. Patients were genotyped for the following polymorphisms: VKORC1-1639G>A, CYP2C9*2, CYP2C9*3, and CYP4F2 V433M. In a 2 × 2 factorial design, patients were randomized to genotype-guided (n = 831) or clinically guided (n = 819) warfarin dosing on days 1 through 11 of therapy and to a target international normalized ratio (INR) of either 1.8 or 2.5. The recommended doses of warfarin were open label, but the patients and clinicians were blinded to study group assignment. The primary end point was the composite of major bleeding, INR of 4 or greater, venous thromboembolism, or death. Patients underwent a screening lower-extremity duplex ultrasound approximately 1 month after arthroplasty. Among 1650 randomized patients (mean age, 72.1 years [SD, 5.4 years]; 63.6% women; 91.0% white), 1597 (96.8%) received at least 1 dose of warfarin therapy and completed the trial (n = 808 in genotype-guided group vs n = 789 in clinically guided group). A total of 87 patients (10.8%) in the genotype-guided group vs 116 patients (14.7%) in the clinically guided warfarin dosing group met at least 1 of the end points (absolute difference, 3.9% [95% CI, 0.7%-7.2%], P = .02; relative rate [RR], 0.73 [95% CI, 0.56-0.95]). The numbers of individual events in the genotype-guided group vs the clinically guided group were 2 vs 8 for major bleeding (RR, 0.24; 95% CI, 0

  19. Comparison of two-dose priming plus 9-month booster with a standard three-dose priming schedule for a ten-valent pneumococcal conjugate vaccine in Nepalese infants: a randomised, controlled, open-label, non-inferiority trial.

    Science.gov (United States)

    Hamaluba, Mainga; Kandasamy, Rama; Upreti, Shyam R; Subedi, Giri R; Shrestha, Shrijana; Bhattarai, Shiva; Gurung, Meeru; Pradhan, Rahul; Voysey, Merryn; Gurung, Santosh; Pradhan, Shachi; Thapa, Anushil K; Maharjan, Rakesh; Kiran, Usha; Kerridge, Simon A; Hinds, Jason; van der Klis, Fiona; Snape, Matthew D; Murdoch, David R; Kelly, Sarah; Kelly, Dominic F; Adhikari, Neelam; Thorson, Stephen; Pollard, Andrew J

    2015-04-01

    Use of pneumococcal conjugate vaccines (PCVs) in resource-poor countries has focused on early infant immunisation with little emphasis on protection in late infancy and beyond. Boosting of the immune response later in infancy might provide improved persistence of immunogenicity into early childhood, however data are scarce. The aim of this study was to investigate if a two-dose prime with booster at age 9 months compared with a three-dose prime-only PCV schedule provided non-inferior immunogenicity in early infancy and superior persistence of antibody responses in early childhood. We did an open-label, randomised, parallel group, controlled trial in healthy infants aged 40-60 days from Kathmandu, Nepal. Participants were randomly allocated (4:4:5 ratio) to receive PCV10 in addition to routine immunisations either as a two-dose prime and boost (2+1), three-dose prime (3+0), or two doses after completion of the initial study phase (0+2). We used a computer generated randomisation list with randomly varying block sizes. We followed up participants at age 2-4 years together with a group of unvaccinated controls. Sera were analysed for opsonophagocytic activity, protein D, and PCV10 serotype-specific IgG. Laboratory staff was masked to intervention group assignment. The primary outcome measure was to determine the proportion of participants in the 2+1 group at age 10 months with specific IgG for serotypes 1, 5, and 14 of at least 0·2 μg/mL in the per-protocol population. The secondary outcomes were non-inferiority (within 10% levels) at age 18 weeks for the proportion of participants in the 2+1 group compared with the 3+0 group with serotypes 1, 5, and 14 specific IgG of at least 0·2 μg/mL; the proportion of participants with PCV10 serotype-specific IgG of at least 0·2 μg/mL and opsonophagocytic activity reciprocal titre of at least 8 at ages 18 weeks and 10 months; and nasopharyngeal pneumococcal serotype-specific carriage rates at age 9 months in each study

  20. A comparison of low-dose risperidone to paroxetine in the treatment of panic attacks: a randomized, single-blind study

    Directory of Open Access Journals (Sweden)

    Galynker Igor I

    2009-05-01

    Full Text Available Abstract Background Because a large proportion of patients with panic attacks receiving approved pharmacotherapy do not respond or respond poorly to medication, it is important to identify additional therapeutic strategies for the management of panic symptoms. This article describes a randomized, rater-blind study comparing low-dose risperidone to standard-of-care paroxetine for the treatment of panic attacks. Methods Fifty six subjects with a history of panic attacks were randomized to receive either risperidone or paroxetine. The subjects were then followed for eight weeks. Outcome measures included the Panic Disorder Severity Scale (PDSS, the Hamilton Anxiety Scale (Ham-A, the Hamilton Depression Rating Scale (Ham-D, the Sheehan Panic Anxiety Scale-Patient (SPAS-P, and the Clinical Global Impression scale (CGI. Results All subjects demonstrated a reduction in both the frequency and severity of panic attacks regardless of treatment received. Statistically significant improvements in rating scale scores for both groups were identified for the PDSS, the Ham-A, the Ham-D, and the CGI. There was no difference between treatment groups in the improvement in scores on the measures PDSS, Ham-A, Ham-D, and CGI. Post hoc tests suggest that subjects receiving risperidone may have a quicker clinical response than subjects receiving paroxetine. Conclusion We can identify no difference in the efficacy of paroxetine and low-dose risperidone in the treatment of panic attacks. Low-dose risperidone appears to be tolerated equally well as paroxetine. Low-dose risperidone may be an effective treatment for anxiety disorders in which panic attacks are a significant component. Trial Registration ClinicalTrials.gov Identifier: NCT100457106

  1. The effect of single low-dose dexamethasone on blood glucose concentrations in the perioperative period: a randomized, placebo-controlled investigation in gynecologic surgical patients.

    Science.gov (United States)

    Murphy, Glenn S; Szokol, Joseph W; Avram, Michael J; Greenberg, Steven B; Shear, Torin; Vender, Jeffery S; Gray, Jayla; Landry, Elizabeth

    2014-06-01

    The effect of single low-dose dexamethasone therapy on perioperative blood glucose concentrations has not been well characterized. In this investigation, we examined the effect of 2 commonly used doses of dexamethasone (4 and 8 mg at induction of anesthesia) on blood glucose concentrations during the first 24 hours after administration. Two hundred women patients were randomized to 1 of 6 groups: Early-control (saline); Early-4 mg (4 mg dexamethasone); Early-8 mg (8 mg dexamethasone); Late-control (saline); Late-4 mg (4 mg dexamethasone); and Late-8 mg (8 mg dexamethasone). Blood glucose concentrations were measured at baseline and 1, 2, 3, and 4 hours after administration in the early groups and at baseline and 8 and 24 hours after administration in the late groups. The incidence of hyperglycemic events (the number of patients with at least 1 blood glucose concentration >180 mg/dL) was determined. Blood glucose concentrations increased significantly over time in all control and dexamethasone groups (from median baselines of 94 to 102 mg/dL to maximum medians ranging from 141 to 161.5 mg/dL, all P < 0.001). Blood glucose concentrations did not differ significantly between the groups receiving dexamethasone (either 4 or 8 mg) and those receiving saline at any measurement time. The incidence of hyperglycemic events did not differ in any of the early (21%-28%, P = 0.807) or late (13%-24%, P = 0.552) groups. Because blood glucose concentrations during the first 24 hours after administration of single low-dose dexamethasone did not differ from those observed after saline administrations, these results suggest clinicians need not avoid using dexamethasone for nausea and vomiting prophylaxis out of concerns related to hyperglycemia.

  2. Methylphenidate Transdermal System in Adults with Past Stimulant Misuse: An Open-Label Trial

    Science.gov (United States)

    McRae-Clark, Aimee L.; Brady, Kathleen T.; Hartwell, Karen J.; White, Kathleen; Carter, Rickey E.

    2011-01-01

    Objective: This 8-week, open-label trial assessed the efficacy of methylphenidate transdermal system (MTS) in 14 adult individuals diagnosed with ADHD and with a history of stimulant misuse, abuse, or dependence. Method: The primary efficacy endpoint was the Wender-Reimherr Adult ADHD Scale (WRAADS), and secondary efficacy endpoints included the…

  3. single dose pharmacokinetics of mefloquine in healthy nigerian

    African Journals Online (AJOL)

    BSN

    Mefloquine 500mg single dose was administered and blood samples were collected ... particle size ODS Hypersil (HETP, Macclesfield, UK) at a pressure of 55 Mpa .... dose to area under the plasma drug concentration - time curve, assuming ...

  4. Multicenter, open-label, exploratory clinical trial with Rhodiola rosea extract in patients suffering from burnout symptoms

    Directory of Open Access Journals (Sweden)

    Kasper S

    2017-03-01

    Full Text Available Siegfried Kasper,1 Angelika Dienel2 1Universitätsklinik für Psychiatrie und Psychotherapie, Medizinische Universität Wien, Wien, Austria; 2Dr Willmar Schwabe GmbH & Co. KG, Karlsruhe, Germany Purpose: This study is the first clinical trial aiming to explore the clinical outcomes in burnout patients treated with Rhodiola rosea. The reported capacity of R. rosea to strengthen the organism against stress and its good tolerability offer a promising approach in the treatment of stress-related burnout. The aim of the treatment was to increase stress resistance, thus addressing the source rather than the symptoms of the syndrome and preventing subsequent diseases associated with a history of burnout. The objective of the trial was to provide the exploratory data required for planning future randomized trials in burnout patients in order to investigate the clinical outcomes of treatment with R. rosea dry extract in this target group.Methods: The study was planned as an exploratory, open-label, multicenter, single-arm trial. A wide range of rating scales were assessed and evaluated in an exploratory data analysis to generate hypotheses regarding clinical courses and to provide a basis for the planning of subsequent studies. A total of 118 outpatients were enrolled. A daily dose of 400 mg R. rosea extract (WS® 1375, Rosalin was administered over 12 weeks. Clinical outcomes were assessed by the German version of the Maslach Burnout Inventory, Burnout Screening Scales I and II, Sheehan Disability Scale, Perceived Stress Questionnaire, Number Connection Test, Multidimensional Mood State Questionnaire, Numerical Analogue Scales for different stress symptoms and impairment of sexual life, Patient Sexual Function Questionnaire, and the Clinical Global Impression Scales. Results: The majority of the outcome measures showed clear improvement over time. Several parameters had already improved after 1 week of treatment and continued to improve further up to

  5. Effect of the Probiotic Saccharomyces boulardii on Cholesterol and Lipoprotein Particles in Hypercholesterolemic Adults: A Single-Arm, Open-Label Pilot Study.

    Science.gov (United States)

    Ryan, Jennifer Joan; Hanes, Douglas Allen; Schafer, Morgan Beth; Mikolai, Jeremy; Zwickey, Heather

    2015-05-01

    Elevated blood cholesterol levels are a major risk factor for coronary artery disease, the leading cause of death worldwide. Probiotics have been investigated as potential cholesterol-lowering therapies, but no previous studies have assessed the effect of the probiotic yeast Saccharomyces boulardii on cholesterol levels in human volunteers. The objective of this study was to examine the effect of S. boulardii on serum cholesterol and lipoprotein particles in hypercholesterolemic adults. This study was a single-arm, open-label pilot study. Twelve hypercholesterolemic participants were recruited into the study; one dropped out. Participants took 5.6×10(10) colony forming unit (CFU) encapsulated S. boulardii (Saccharomyces cerevisiae var. boulardii CNCM I-1079) twice daily for an 8-week period. Fasting concentrations of cholesterol (total cholesterol, low-density lipoprotein-cholesterol [LDL-C], high-density lipoprotein-cholesterol [HDL-C], and triglycerides), lipoprotein particles (very-low-density lipoprotein-particle [VLDL-P], remnant lipoprotein particle [RLP-P], total LDL-P, LDL III-P, LDL IV-P, total HDL-P, and HDL 2b-P), and additional cardiovascular biomarkers (apo B-100, lipoprotein [a], high-sensitivity C-reactive protein, homocysteine, fibrinogen, and insulin) were measured at baseline, after 4 weeks, and after 8 weeks. Remnant lipoprotein particles decreased by 15.5% (p=0.03) over the 8-week period. The remaining outcome measures were not significantly altered. In this pilot study, 8 weeks of daily supplementation with S. boulardii lowered remnant lipoprotein, a predictive biomarker and potential therapeutic target in the treatment and prevention of coronary artery disease.

  6. N-Acetylcysteine for Nonsuicidal Self-Injurious Behavior in Adolescents: An Open-Label Pilot Study.

    Science.gov (United States)

    Cullen, Kathryn R; Klimes-Dougan, Bonnie; Westlund Schreiner, Melinda; Carstedt, Patricia; Marka, Nicholas; Nelson, Katharine; Miller, Michael J; Reigstad, Kristina; Westervelt, Ana; Gunlicks-Stoessel, Meredith; Eberly, Lynn E

    2018-03-01

    Nonsuicidal self-injury (NSSI) is common in adolescents and young adults, and few evidence-based treatments are available for this significant problem. N-acetylcysteine (NAC) is a widely available nutritional supplement that has been studied in some psychiatric disorders relevant to NSSI including mood and addictive disorders. This pilot study tested the use of NAC as a potential treatment for NSSI in youth. Thirty-five female adolescents and young adults with NSSI aged 13-21 years were enrolled in this study that had an open-label, single-arm study design. All participants were given oral NAC as follows: 600 mg twice daily (weeks 1-2), 1200 mg twice daily (weeks 3-4), and 1800 mg twice daily (weeks 5-8). Patients were seen every 2 weeks throughout the trial, at which time youth reported the frequency of NSSI episodes. Levels of depression, impulsivity, and global psychopathology were measured at baseline and at the end of the trial using the Beck Depression Inventory-II (BDI-II), Barratt Impulsivity Scale, and Symptoms Checklist-90 (SCL-90). About two-thirds of the enrolled female youth completed the trial (24/35). NAC was generally well tolerated in this sample. NAC treatment was associated with a significant decrease in NSSI frequency at visit 6 and visit 8 compared to baseline. We also found that depression scores and global psychopathology scores (but not impulsivity scores) decreased after NAC treatment. Decrease in NSSI was not correlated with decrease in BDI-II or SCL-90 scores, suggesting these might be independent effects. We provide preliminary evidence that NAC may have promise as a potential treatment option for adolescents with NSSI. The current results require follow-up with a randomized, placebo-controlled trial to confirm efficacy.

  7. Metabolism of tritium- and carbon-14-labeled tiamulin in dogs, rats, and pigs.

    Science.gov (United States)

    Dreyfuss, J; Singhvi, S M; Shaw, J M; Egli, P; Ross, J J; Czok, R; Nefzger-Biessels, M; Battig, F; Schuster, I; Schmook, F

    1979-05-01

    The metabolism of tiamulin hydrogen fumarate, labeled with 3H, 14C, or both, was studied in dogs, rats, and weanling pigs. After a dose of radiolabeled tiamulin, all three species excreted more radioactivity in feces (via bile) than in urine. Dogs absorbed 86% of a single oral dose of tiamulin-3H, and the disposition of the compound was similar after a single or multiple dosage regimen. The ratio of antimicrobial activity to total radioactivity in dog plasma was only about 0.25, and was still less in dog urine. After dosing with tiamulin-14C, rats and pigs excreted at least 1% of the dose as 14CO2 in expired air. In dual-labeled studies, pigs excreted less total 14C than 3H and had greater residues of 14C than 3H in edible tissues, blood, and plasma. After the administration of tiamulin-14C to pigs, radioactivity was incorporated into liver glycogen, indicating metabolic cleavage of the side chain of tiamulin. Tiamulin-3H is the isotopically-labeled compound of choice for studying metabolism and tissue residues in animals.

  8. Safety, pharmacokinetics and efficacy findings in an open-label, single-arm study of weekly paclitaxel plus lapatinib as first-line therapy for Japanese women with HER2-positive metastatic breast cancer.

    Science.gov (United States)

    Inoue, Kenichi; Kuroi, Katsumasa; Shimizu, Satoru; Rai, Yoshiaki; Aogi, Kenjiro; Masuda, Norikazu; Nakayama, Takahiro; Iwata, Hiroji; Nishimura, Yuichiro; Armour, Alison; Sasaki, Yasutsuna

    2015-12-01

    Lapatinib is the human epidermal growth factor receptor 2 (HER2) targeting agent approved globally for HER2-positive metastatic breast cancer (MBC). The efficacy, safety and pharmacokinetics (PK) of lapatinib combined with paclitaxel (L+P) were investigated in this study, to establish clear evidence regarding the combination in Japanese patients. In this two-part, single-arm, open-label study, the tolerability of L+P as first-line treatment in Japanese patients with HER2-positive MBC was evaluated in six patients in the first part, and the safety, efficacy and PK were evaluated in a further six patients (making a total of twelve patients) in the second part. Eligible women were enrolled and received lapatinib 1500 mg once daily and paclitaxel 80 mg/m(2) weekly for at least 6 cycles. The only dose-limiting toxicity reported was Grade 3 diarrhea in one patient. The systemic exposure to maximum plasma concentration and area under the plasma concentration curve (AUC) for lapatinib, as well as the AUC of paclitaxel, were increased when combined. The most common adverse events (AEs) related to the study treatment were alopecia, diarrhea and decreased hemoglobin. The majority of drug-related AEs were Grade 1 or 2. The median overall survival was 35.6 months (95 % confidence interval 23.9, not reached). The response rate and clinical benefit rate were both 83 % (95 % confidence interval 51.6, 97.9). The L+P treatment was well tolerated in Japanese patients with HER2-positive MBC. Although the PK profiles of lapatinib and paclitaxel influenced each other, the magnitudes were not greatly different from those in non-Japanese patients.

  9. Randomized Crossover Comparison of the Short-Term Efficacy and Safety of Single Half-Dose Silodosin and Tamsulosin Hydrochoride in Men With Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia.

    Science.gov (United States)

    Takeshita, Hideki; Moriyama, Shingo; Arai, Yoshiaki; Washino, Satoshi; Saito, Kimitoshi; Chiba, Koji; Horiuchi, Susumu; Noro, Akira

    2016-01-01

    To compare the efficacy and safety of single half-dose silodosin and single full-dose tamsulosin in Japanese men with lower urinary tract symptoms secondary to benign prostatic hyperplasia (LUTS/BPH). Japanese men aged ≥50 years with LUTS/BPH and an International Prostate Symptom Score (IPSS) of ≥8 were enrolled in the randomized crossover study and divided into silodosin-preceding (S-T) and tamsulosin-preceding (T-S) groups. The S-T group received 4 mg silodosin once daily for 4 weeks followed by 0.2 mg tamsulosin once daily for 4 weeks. The T-S group received the reverse treatment sequence. A washout period prior to drug crossover was not included. Subjective and objective efficacy parameters including IPSS, quality of life (QOL) index, uroflowmetry, and safety were compared between the two groups. Thirty of 34 men (S-T group n = 16; T-S group n = 14) completed the study. Both drugs significantly improved all IPSS items and QOL index in the first treatment period. Subjective improvement in nocturia by silodosin was observed in both the first and crossover treatment periods. Objective improvement in maximum flow rate by silodosin was only observed in the first treatment period. Adverse events occurred more frequently with silodosin than with tamsulosin; however, none of the adverse events required treatment discontinuation. Ejaculation disorders occurred in three participants (10%) and were associated with silodosin use. Single half-dose silodosin has a similar efficacy to full-dose tamsulosin in Japanese men with LUTS/BPH and thus, may represent an effective, safe, and affordable treatment option. © 2015 Wiley Publishing Asia Pty Ltd.

  10. Pharmacodynamics of vildagliptin in patients with type 2 diabetes during OGTT

    DEFF Research Database (Denmark)

    He, Yan-Ling; Wang, Yibin; Bullock, Julie M

    2007-01-01

    This randomized, open-label, placebo-controlled, 7-period crossover study assessed dose-response relationships following single oral doses (10-400 mg) of vildagliptin in 16 patients with type 2 diabetes mellitus. Plasma levels of parent drug, dipeptidyl peptidase-4 activity, glucose, insulin...... of dipeptidyl peptidase-4 inhibition were dose dependent, but >90% inhibition occurred within 45 minutes and was maintained for >/=4 hours after each dose. Glucose excursions and glucagon levels during oral glucose tolerance tests were significantly and similarly decreased after each dose of vildagliptin......, and insulin levels were significantly and similarly increased after each dose level. Unlike findings during mixed-meal challenges, vildagliptin increases plasma insulin levels during oral glucose tolerance tests in patients with type 2 diabetes mellitus....

  11. Comparative prospective randomized trial: laparoscopic versus open common bile duct exploration

    Directory of Open Access Journals (Sweden)

    Vladimir Grubnik

    2011-06-01

    Full Text Available Introduction: Single-stage laparoscopic procedures for common bile duct (CBD stones are an alternative treatmentoption to two-stage endo-laparoscopic treatment and to open choledocholithotomy. Several reports have demonstratedthe feasibility, safety, efficiency and cost-effectiveness of laparoscopic techniques.Aim: To analyse the safety and benefits of laparoscopic compared to open common bile duct (CBD exploration.Material and methods: The prospective randomized trial included a total of 256 patients with CBD stones operated from2005 to 2009 in a single centre. The male/female ratio was 82/174, with a median age 62.3 ±5.8 years (range 27 to 87years. There were two groups of patients. Group I: laparoscopic CBD exploration (138 patients. Group II: open CBD exploration(118 patients. Patient comorbidity was assessed by means of the American Society of Anesthesiologists (ASA classification;ASA II – 109 patients, ASA III – 59 patients. Bile duct stones were visualized preoperatively by means of US examinationin 129 patients, by means of ERCP in 26 patients, and by magnetic resonance cholangiopancreatography (MRCPin 72 patients. Preoperative evaluation was done through medical history, biochemical tests and ultrasonography.Results: The mean duration of laparoscopic procedures was 82 min (range 40-160 min. The mean duration of openprocedures was 90 min (range 60-150 min. Mean blood loss was much lower in the laparoscopic group than in theopen group (20 ±2 v.s 285 ±27, p < 0.01. Postoperative complications were observed in 7 patients of the laparoscopicgroup and in 15 patients in the open group (p < 0.01. Laparoscopic common bile duct exploration was performedthrough a trans-cystic approach in 76 patients and via choledochotomy in 62 patients. The transcystic approach wassuccessful in 76 patients (74.5%. External drainage was used in 25 (32.8% patients with the transcystic approach.Conclusions: Laparoscopic CBD exploration can be performed with

  12. Community transmission of type 2 poliovirus after cessation of trivalent oral polio vaccine in Bangladesh: an open-label cluster-randomised trial and modelling study.

    Science.gov (United States)

    Taniuchi, Mami; Famulare, Michael; Zaman, Khalequ; Uddin, Md Jashim; Upfill-Brown, Alexander M; Ahmed, Tahmina; Saha, Parimalendu; Haque, Rashidul; Bandyopadhyay, Ananda S; Modlin, John F; Platts-Mills, James A; Houpt, Eric R; Yunus, Mohammed; Petri, William A

    2017-10-01

    Trivalent oral polio vaccine (tOPV) was replaced worldwide from April, 2016, by bivalent types 1 and 3 oral polio vaccine (bOPV) and one dose of inactivated polio vaccine (IPV) where available. The risk of transmission of type 2 poliovirus or Sabin 2 virus on re-introduction or resurgence of type 2 poliovirus after this switch is not understood completely. We aimed to assess the risk of Sabin 2 transmission after a polio vaccination campaign with a monovalent type 2 oral polio vaccine (mOPV2). We did an open-label cluster-randomised trial in villages in the Matlab region of Bangladesh. We randomly allocated villages (clusters) to either: tOPV at age 6 weeks, 10 weeks, and 14 weeks; or bOPV at age 6 weeks, 10 weeks, and 14 weeks and either one dose of IPV at age 14 weeks or two doses of IPV at age 14 weeks and 18 weeks. After completion of enrolment, we implemented an mOPV2 vaccination campaign that targeted 40% of children younger than 5 years, regardless of enrolment status. The primary outcome was Sabin 2 incidence in the 10 weeks after the campaign in per-protocol infants who did not receive mOPV2, as assessed by faecal shedding of Sabin 2 by reverse transcriptase quantitative PCR (RT-qPCR). The effect of previous immunity on incidence was also investigated with a dynamical model of poliovirus transmission to observe prevalence and incidence of Sabin 2 virus. This trial is registered at ClinicalTrials.gov, number NCT02477046. Between April 30, 2015, and Jan 14, 2016, individuals from 67 villages were enrolled to the study. 22 villages (300 infants) were randomly assigned tOPV, 23 villages (310 infants) were allocated bOPV and one dose of IPV, and 22 villages (329 infants) were assigned bOPV and two doses of IPV. Faecal shedding of Sabin 2 in infants who did not receive the mOPV2 challenge did not differ between children immunised with bOPV and one or two doses of IPV and those who received tOPV (15 of 252 [6%] vs six of 122 [4%]; odds ratio [OR] 1·29, 95% CI 0

  13. Hypoxia-Inducible Factor Pathway Inhibition Resolves Tumor Hypoxia and Improves Local Tumor Control After Single-Dose Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Helbig, Linda [OncoRay–National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Koi, Lydia [OncoRay–National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Deutsches Konsortium für Translationale Krebsforschung, Site Dresden, Dresden (Germany); Brüchner, Kerstin [Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Institute of Radiooncology Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Gurtner, Kristin [Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Hess-Stumpp, Holger; Unterschemmann, Kerstin [Global Drug Discovery, Bayer Pharma, Berlin (Germany); Pruschy, Martin [Radiation Oncology, University of Zurich, Zurich (Switzerland); and others

    2014-01-01

    Purpose: To study the effects of BAY-84-7296, a novel orally bioavailable inhibitor of mitochondrial complex I and hypoxia-inducible factor 1 (HIF-1) activity, on hypoxia, microenvironment, and radiation response of tumors. Methods and Materials: UT-SCC-5 and UT-SCC-14 human squamous cell carcinomas were transplanted subcutaneously in nude mice. When tumors reached 4 mm in diameter BAY-84-7296 (Bayer Pharma AG) or carrier was daily administered to the animals. At 7 mm tumors were either excised for Western blot and immunohistologic investigations or were irradiated with single doses. After irradiation animals were randomized to receive BAY-84-7296 maintenance or carrier. Local tumor control was evaluated 150 days after irradiation, and the dose to control 50% of tumors (TCD{sub 50}) was calculated. Results: BAY-84-7296 decreased nuclear HIF-1α expression. Daily administration of inhibitor for approximately 2 weeks resulted in a marked decrease of pimonidazole hypoxic fraction in UT-SCC-5 (0.5% vs 21%, P<.0001) and in UT-SCC-14 (0.3% vs 19%, P<.0001). This decrease was accompanied by a significant increase in fraction of perfused vessels in UT-SCC-14 but not in UT-SCC-5. Bromodeoxyuridine and Ki67 labeling indices were significantly reduced only in UT-SCC-5. No significant changes were observed in vascular area or necrosis. BAY-84-7296 before single-dose irradiation significantly decreased TCD{sub 50}, with an enhancement ratio of 1.37 (95% confidence interval [CI] 1.13-1.72) in UT-SCC-5 and of 1.55 (95% CI 1.26-1.94) in UT-SCC-14. BAY-84-7296 maintenance after irradiation did not further decrease TCD{sub 50}. Conclusions: BAY-84-7296 resulted in a marked decrease in tumor hypoxia and substantially reduced radioresistance of tumor cells with the capacity to cause a local recurrence after irradiation. The data suggest that reduction of cellular hypoxia tolerance by BAY-84-7296 may represent the primary biological mechanism underlying the observed enhancement of

  14. Efficacy, Safety, and Dose of Pafuramidine, a New Oral Drug for Treatment of First Stage Sleeping Sickness, in a Phase 2a Clinical Study and Phase 2b Randomized Clinical Studies.

    Directory of Open Access Journals (Sweden)

    Christian Burri

    2016-02-01

    Full Text Available Sleeping sickness (human African trypanosomiasis [HAT] is caused by protozoan parasites and characterized by a chronic progressive course, which may last up to several years before death. We conducted two Phase 2 studies to determine the efficacy and safety of oral pafuramidine in African patients with first stage HAT.The Phase 2a study was an open-label, non-controlled, proof-of-concept study where 32 patients were treated with 100 mg of pafuramidine orally twice a day (BID for 5 days at two trypanosomiasis reference centers (Angola and the Democratic Republic of the Congo [DRC] between August 2001 and November 2004. The Phase 2b study compared pafuramidine in 41 patients versus standard pentamidine therapy in 40 patients. The Phase 2b study was open-label, parallel-group, controlled, randomized, and conducted at two sites in the DRC between April 2003 and February 2007. The Phase 2b study was then amended to add an open-label sequence (Phase 2b-2, where 30 patients received pafuramidine for 10 days. The primary efficacy endpoint was parasitologic cure at 24 hours (Phase 2a or 3 months (Phase 2b after treatment completion. The primary safety outcome was the rate of occurrence of World Health Organization Toxicity Scale Grade 3 or higher adverse events. All subjects provided written informed consent.Pafuramidine for the treatment of first stage HAT was comparable in efficacy to pentamidine after 10 days of dosing. The cure rates 3 months post-treatment were 79% in the 5-day pafuramidine, 100% in the 7-day pentamidine, and 93% in the 10-day pafuramidine groups. In Phase 2b, the percentage of patients with at least 1 treatment-emergent adverse event was notably higher after pentamidine treatment (93% than pafuramidine treatment for 5 days (25% and 10 days (57%. These results support continuation of the development program for pafuramidine into Phase 3.

  15. Efficacy, Safety, and Dose of Pafuramidine, a New Oral Drug for Treatment of First Stage Sleeping Sickness, in a Phase 2a Clinical Study and Phase 2b Randomized Clinical Studies.

    Science.gov (United States)

    Burri, Christian; Yeramian, Patrick D; Allen, James L; Merolle, Ada; Serge, Kazadi Kyanza; Mpanya, Alain; Lutumba, Pascal; Mesu, Victor Kande Betu Ku; Bilenge, Constantin Miaka Mia; Lubaki, Jean-Pierre Fina; Mpoto, Alfred Mpoo; Thompson, Mark; Munungu, Blaise Fungula; Manuel, Francisco; Josenando, Théophilo; Bernhard, Sonja C; Olson, Carol A; Blum, Johannes; Tidwell, Richard R; Pohlig, Gabriele

    2016-02-01

    Sleeping sickness (human African trypanosomiasis [HAT]) is caused by protozoan parasites and characterized by a chronic progressive course, which may last up to several years before death. We conducted two Phase 2 studies to determine the efficacy and safety of oral pafuramidine in African patients with first stage HAT. The Phase 2a study was an open-label, non-controlled, proof-of-concept study where 32 patients were treated with 100 mg of pafuramidine orally twice a day (BID) for 5 days at two trypanosomiasis reference centers (Angola and the Democratic Republic of the Congo [DRC]) between August 2001 and November 2004. The Phase 2b study compared pafuramidine in 41 patients versus standard pentamidine therapy in 40 patients. The Phase 2b study was open-label, parallel-group, controlled, randomized, and conducted at two sites in the DRC between April 2003 and February 2007. The Phase 2b study was then amended to add an open-label sequence (Phase 2b-2), where 30 patients received pafuramidine for 10 days. The primary efficacy endpoint was parasitologic cure at 24 hours (Phase 2a) or 3 months (Phase 2b) after treatment completion. The primary safety outcome was the rate of occurrence of World Health Organization Toxicity Scale Grade 3 or higher adverse events. All subjects provided written informed consent. Pafuramidine for the treatment of first stage HAT was comparable in efficacy to pentamidine after 10 days of dosing. The cure rates 3 months post-treatment were 79% in the 5-day pafuramidine, 100% in the 7-day pentamidine, and 93% in the 10-day pafuramidine groups. In Phase 2b, the percentage of patients with at least 1 treatment-emergent adverse event was notably higher after pentamidine treatment (93%) than pafuramidine treatment for 5 days (25%) and 10 days (57%). These results support continuation of the development program for pafuramidine into Phase 3.

  16. The dose dependency of the over-dispersion of quartz OSL single grain dose distributions

    International Nuclear Information System (INIS)

    Thomsen, Kristina J.; Murray, Andrew; Jain, Mayank

    2012-01-01

    The use of single grain quartz OSL dating has become widespread over the past decade, particularly with application to samples likely to have been incompletely bleached before burial. By reducing the aliquot size to a single grain the probability of identifying the grain population most likely to have been well-bleached at deposition is maximised and thus the accuracy with which the equivalent dose can be determined is – at least in principle – improved. However, analysis of single grain dose distributions requires knowledge of the dispersion of the well-bleached part of the dose distribution. This can be estimated by measurement of a suitable analogue, e.g. a well-bleached aeolian sample, but this requires such an analogue to be available, and in addition the assumptions that the sample is in fact a) well-bleached, and b) has a similar dose rate heterogeneity to the fossil deposit. Finally, it is an implicit assumption in such analysis that any over-dispersion is not significantly dose dependent. In this study we have undertaken laboratory investigations of the dose dependency of over-dispersion using a well-bleached modern sample with an average measured dose of 36 ± 3 mGy. This sample was prepared as heated (750 °C for 1 h), bleached and untreated portions which were then given uniform gamma doses ranging from 100 mGy to 208 Gy. We show that for these samples the relative laboratory over-dispersion is not constant as a function of dose and that the over-dispersion is smaller in heated samples. We also show that the dim grains in the distributions have a greater over-dispersion than the bright grains, implying that insensitive samples will have greater values of over-dispersion than sensitive samples.

  17. A randomized, phase 1/2 trial of the safety, tolerability, and immunogenicity of bivalent rLP2086 meningococcal B vaccine in healthy infants.

    Science.gov (United States)

    Martinon-Torres, Federico; Gimenez-Sanchez, Francisco; Bernaola-Iturbe, Enrique; Diez-Domingo, Javier; Jiang, Qin; Perez, John L

    2014-09-08

    Neisseria meningitidis serogroup B (MnB) is a major cause of invasive meningococcal disease in infants. A conserved, surface-exposed lipoprotein, LP2086 (a factor H-binding protein [fHBP]), is a promising MnB vaccine target. A bivalent, recombinant vaccine targeting the fHBP (rLP2086) of MnB was developed. This phase 1/2 clinical study was designed to assess the immunogenicity, safety, and tolerability of a 4-dose series of the rLP2086 vaccine at 20-, 60-, 120-, or 200-μg dose levels in vaccine-naive infants when given with routine childhood vaccines. The study was to consist of two phases: a single-blind sentinel phase and an open-label full enrollment phase. During the sentinel phase, randomization of subjects to the next higher dose was delayed pending a 14-day safety review of dose 1 of the preceding dose cohort. The full enrollment phase was to occur after completion of the sentinel phase. Local reactions were generally mild and adverse events infrequent; however, after only 46 infants were randomized into the study, fever rates were 64% and 90% in subjects receiving one 20- or 60-μg rLP2086 dose, respectively. Most fevers were group and 1 subject in the 60-μg group experienced fevers >39.0°C; no fevers were >40.0°C. Due to these high fever rates, the study was terminated early. No immunogenicity data were collected. This report discusses the safety and acceptability of rLP2086 in infants after one 20- or 60-μg dose. Due to the high fever rate experienced in the 20- and 60-μg groups, rLP2086 in the current formulation may not be acceptable for infants. Copyright © 2014. Published by Elsevier Ltd.

  18. Comparison of efficacy of transversus abdominis plane block and iliohypogastric/ilioinguinal nerve block for postoperative pain management in patients undergoing inguinal herniorrhaphy with spinal anesthesia: a prospective randomized controlled open-label study.

    Science.gov (United States)

    Okur, Onur; Tekgul, Zeki Tuncel; Erkan, Nazif

    2017-10-01

    The purpose of this study was to compare the effects of lateral abdominal transversus abdominis plane block (TAP block) and iliohypogastric/ilioinguinal nerve block (IHINB) under ultrasound guidance for postoperative pain management of inguinal hernia repair. Secondary purposes were to compare the complication rates of the two techniques and to examine the effects of TAP block and IHINB on chronic postoperative pain. This was a prospective randomized controlled open-label study. After approval of the Research Ethics Board, a total of 90 patients were allocated to three groups of 30 by simple randomized sampling as determined with a priori power analysis. Peripheral nerve blocks (TAP block or IHINB) were administered to patients following subarachnoid block according to their allocated group. Patient pain scores, additional analgesic requirements and complication rates were recorded periodically and compared. Pain scores were significantly lower in the study groups (p block group [GT] 266.6 ± 119.7 min; IHINB group [GI] 247.2 ± 128.7 min; and control group [GC] 79.1 ± 66.2 min; p block or IHINB for patients undergoing inguinal herniorrhaphy reduces the intensity of both acute and chronic postoperative pain and additional analgesic requirements.

  19. Estimation of organ cumulated activities and absorbed doses on intakes of several {sup 11}C labelled radiopharmaceuticals from external measurement with thermoluminescent dosimeters

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, Takashi; Hayashi, Yoshiharu; Watabe, Hiroshi; Matsumoto, Masaki; Horikawa, Tohru; Fujiwara, Takehiko; Ito, Masatoshi; Yanai, Kazuhiko [Cyclotron and Radioisotope Center, Tohoku University, Aoba, Aramaki, Sendai 980-77 (Japan)

    1998-02-01

    We have developed a method for obtaining the cumulated activities in organs from radionuclides, which are injected into the patient in nuclear medicine procedures, by external exposure measurement with thermoluminescent dosimeters (TLDs) which are attached to the patient's body surface close to source organs to obtain information on body-surface doses. As the surface dose is connected to the cumulated activities in source organs through radiation transmission in the human body which can be estimated with the aid of a mathematical phantom, the organ cumulated activities can be obtained by the inverse transform method. The accuracy of this method was investigated by using a water phantom in which several gamma-ray volume sources of known activity were placed to simulate source organs. We then estimated by external measurements the organ cumulated activities and absorbed doses in subjects to whom the radiopharmaceuticals {sup 11}C-labelled Doxepin, {sup 11}C-labelled YM09151-2 and {sup 11}C-labelled Benzotropin were administered in clinical nuclear medicine procedures. The cumulated activities in the brain obtained with TLDs for Doxepin and YM09151-2 are 63.6{+-}6.2 and 32.1{+-}12.0 kBq h MBq{sup -1} respectively, which are compared with the respective values of 33.3{+-}9.9 and 23.9{+-}6.2 kBq h MBq{sup -1} with direct PET (positron emission tomography) measurements. The agreement between the two methods is within a factor of two. The effective doses of Doxepin, YM09151-2 and Benzotropin are determined as 6.92x10{sup -3}, 7.08x10{sup -3} and 7.65x10{sup -3} mSv MBq{sup -1} respectively with the TLD method. This method has great advantages, in that cumulated activities in several organs can be obtained easily with a single procedure, and the measurements of body surface doses are performed simultaneously with the nuclear medicine procedure, as TLDs are too small to interfere with other medical measurements. (author)

  20. The effectiveness of low-dose and high-dose tranexamic acid in posterior lumbar interbody fusion: a double-blinded, placebo-controlled randomized study.

    Science.gov (United States)

    Kim, Ki-Tack; Kim, Cheung-Kue; Kim, Yong-Chan; Juh, Hyung-Suk; Kim, Hyo-Jong; Kim, Hyeon-Soo; Hong, Se Jung; Hey, Hwee Weng Dennis

    2017-11-01

    Tranexamic acid is a proven drug used for reduction of intraoperative blood loss in spinal surgery. However, optimal dosing considering risk/benefits is not well established owing to the heterogeneity in patient selection and surgical procedures of previous studies. This study aimed to evaluate the effectiveness and safety of various tranexamic acid regimens in reducing perioperative blood loss in single-level posterior lumbar interbody fusion (PLIF). Patients were randomly grouped into three different interventions: low-dose tranexamic acid (LD), high-dose tranexamic acid (HD), and placebo-controlled (PC) groups. The HD and LD groups received 10 and 5 mg/kg of bolus loading dose and 2 and 1 mg/kg of continuous infusion until 5 h after surgery, respectively. Data on patient demographics and preoperative and 24-h postoperative laboratory values were collected. Outcome parameters include intraoperative blood loss, 24-h postoperative blood loss, and blood loss during removal of the last drain. Seventy-two patients (mean age 63.3 ± 7.6 years) showed similar baseline characteristics. Intraoperatively, blood loss was reduced by the administration of tranexamic acid (P = 0.04), contributed predominantly by a difference between the LD and HD groups (123 mL; P tranexamic acid use were noted. Tranexamic acid administration for single-level PLIF was effective and safe in reducing perioperative blood loss in a dose-dependent manner. An HD regimen comprising 10 mg/kg of bolus loading dose and 2 mg/kg/h of continuous infusion is recommended. Level 1 study according to Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence.

  1. A comparison of a single-dose and a seven-day treatment with Amoxicillin in asymptomatic bacteriuria in pregnancy

    Directory of Open Access Journals (Sweden)

    Niro Manesh S

    1994-05-01

    Full Text Available In this study, 1600 pregnant women who had referred to two prenatal clinics (Imam Khomeini and Mirza Kochek-Khan were investigated. Ninety cases of asymptomatic bacteriuria were observed; 77 of those cooperated with us until the end of our study. The subjects, who were within the 14-36 weeks of gestational age, were randomly divided into two groups: Group A received the medicine (Amoxicillin in a single-dose (3gr.; and, group B received it within seven days (1gr. TDS. The rate of recovery (65% in group A and 56.8% in group B, based on chi-squared test, showed no significant difference (P=0.747%. According to the results of this study, we can conclude that single-dose treatment has the same value as a seven-day treatment and the advantages such as decreased total dose, lower cost, and a better patient compliance.

  2. The Duration of Intestinal Immunity After an Inactivated Poliovirus Vaccine Booster Dose in Children Immunized With Oral Vaccine: A Randomized Controlled Trial.

    Science.gov (United States)

    John, Jacob; Giri, Sidhartha; Karthikeyan, Arun S; Lata, Dipti; Jeyapaul, Shalini; Rajan, Anand K; Kumar, Nirmal; Dhanapal, Pavithra; Venkatesan, Jayalakshmi; Mani, Mohanraj; Hanusha, Janardhanan; Raman, Uma; Moses, Prabhakar D; Abraham, Asha; Bahl, Sunil; Bandyopadhyay, Ananda S; Ahmad, Mohammad; Grassly, Nicholas C; Kang, Gagandeep

    2017-02-15

    In 2014, 2 studies showed that inactivated poliovirus vaccine (IPV) boosts intestinal immunity in children previously immunized with oral poliovirus vaccine (OPV). As a result, IPV was introduced in mass campaigns to help achieve polio eradication. We conducted an open-label, randomized, controlled trial to assess the duration of the boost in intestinal immunity following a dose of IPV given to OPV-immunized children. Nine hundred healthy children in Vellore, India, aged 1-4 years were randomized (1:1:1) to receive IPV at 5 months (arm A), at enrollment (arm B), or no vaccine (arm C). The primary outcome was poliovirus shedding in stool 7 days after bivalent OPV challenge at 11 months. For children in arms A, B, and C, 284 (94.7%), 297 (99.0%), and 296 (98.7%), respectively, were eligible for primary per-protocol analysis. Poliovirus shedding 7 days after challenge was less prevalent in arms A and B compared with C (24.6%, 25.6%, and 36.4%, respectively; risk ratio 0.68 [95% confidence interval: 0.53-0.87] for A versus C, and 0.70 [0.55-0.90] for B versus C). Protection against poliovirus remained elevated 6 and 11 months after an IPV boost, although at a lower level than reported at 1 month. CTRI/2014/09/004979. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

  3. A Randomized, Open-Label, Comparative Study of Efficacy and Safety of Tolterodine Combined with Tamsulosin or Doxazosin in Patients with Benign Prostatic Hyperplasia

    Science.gov (United States)

    Cao, Yanwei; Wang, Yonghua; Guo, Lei; Yang, Xuecheng; Chen, Tao; Niu, Haitao

    2016-01-01

    Background Benign prostatic hyperplasia (BPH), a common disease in men over age 50 years, often causes bladder outlet obstruction and lower urinary tract symptoms (LUTS). Alpha blockers in combination with muscarinic receptor antagonists may have the potential to improve symptoms. This study aimed to assess the efficacy and safety of doxazosin or tamsulosin combined with tolterodine extend release (ER) in patients with BPH and LUTS. Material/Methods In a prospective, randomized, open-label study (ChiCTR-IPR-15005763), 220 consecutive men with BPH and LUTS were allocated to receive doxazosin 4 mg and tolterodine ER 4 mg per day (doxazosin group) or tamsulosin 0.2 mg and tolterodine ER 4 mg per day (tamsulosin group). Treatment lasted 12 weeks. The primary endpoint was the international prostatic symptom score (IPSS). Secondary endpoints were quality of life (QoL) and maximum flow rate (Qmax), which were evaluated at 0, 6, and 12 weeks, and urodynamic parameters assessed at 0 and 12 weeks. Results A total of 192 patients completed the trial. Baseline measurements showed no differences between the groups. After 6 weeks, IPSS improved in both groups and QoL was significantly better in the doxazosin group (P=0.01). After 12 weeks, Qmax, IPSS, QoL, intravesical pressure (Pves), and bladder compliance (BC) in the doxazosin group were significantly better than in the tamsulosin group (P=0.03, P<0.001, P<0.001, P=0.027, and P=0.044, respectively). Conclusions Administration of alpha blockers combined with muscarinic receptor blocker for 12 weeks improved LUTS in men with BPH. PMID:27260129

  4. The comparison between limited open carpal tunnel release using direct vision and tunneling technique and standard open carpal tunnel release: a randomized controlled trial study.

    Science.gov (United States)

    Suppaphol, Sorasak; Worathanarat, Patarawan; Kawinwongkovit, Viroj; Pittayawutwinit, Preecha

    2012-04-01

    To compare the operative outcome of carpal tunnel release between limited open carpal tunnel release using direct vision and tunneling technique (group A) with standard open carpal tunnel release (group B). Twenty-eight patients were enrolled in the present study. A single blind randomized control trial study was conducted to compare the postoperative results between group A and B. The study parameters were Levine's symptom severity and functional score, grip and pinch strength, and average two-point discrimination. The postoperative results between two groups were comparable with no statistical significance. Only grip strength at three months follow up was significantly greater in group A than in group B. The limited open carpal tunnel release in the present study is effective comparable to the standard open carpal tunnel release. The others advantage of this technique are better cosmesis and improvement in grip strength at the three months postoperative period.

  5. Pharmacokinetics and pharmacodynamics of MD1003 (high-dose biotin) in the treatment of progressive multiple sclerosis.

    Science.gov (United States)

    Peyro Saint Paul, Laure; Debruyne, Danièle; Bernard, Delphine; Mock, Donald M; Defer, Gilles L

    2016-01-01

    Multiple sclerosis (MS) is a chronic, potentially highly disabling neurological disorder. No disease-modifying treatments are approved in the progressive and not active forms of the disease. High doses of biotin were tested in an open-label pilot study involving 23 patients with progressive MS and reported positive results. A randomized, double-blind, placebo-controlled trial in 154 progressive MS patients confirmed the beneficial effect of MD1003 (high-dose biotin) on reversing or stabilizing disability progression, with a good safety profile. It is proposed that MD1003 in progressive MS 1) increases energy production in demyelinated axons and/or 2) enhances myelin synthesis in oligodendrocytes. Biotin is highly bioavailable; absorption and excretion are rapid. The major route of elimination is urinary excretion. A high oral dose of biotin seems generally well tolerated but a few important safety concerns were identified: 1) teratogenicity in one species and 2) interference with some biotin-based laboratory immunoassays. The animal toxicity data are limited at such high doses. Further preclinical studies would be useful to address the mechanism of action of MD1003. Assessment of clinical benefit duration in responders will be also very important to set. Results of randomized, placebo-controlled trial are reassuring and provide hope for the treatment of progressive MS.

  6. Success and spontaneous pregnancy rates following systemic methotrexate versus laparoscopic surgery for tubal pregnancies: A randomized trial

    DEFF Research Database (Denmark)

    Krag Moeller, Lars Bo; Moeller, Charlotte; Thomsen, Sten Grove

    2009-01-01

    . A total of 106 women diagnosed with ectopic pregnancy (EP). Methods. Between March 1997 and September 2000, 1,265 women were diagnosed with EP, 395 (31%) were eligible, 109 (9%) were randomized of whom 106 had an EP. The study was originally powered to a sample size of 422 patients. The women were......Objective. To determine which treatment should be offered to women with a non-ruptured tubal pregnancy: a single dose of methotrexate (MTX) or laparoscopic surgery. Design. Prospective, randomized, open multicenter study. Setting. Seven Danish departments of obstetrics and gynecology. Sample...... (n.s.). Conclusions. In women with an EP, who are hemodynamically stable and wishing to preserve their fertility, medical treatment with single dose MTX tends to be equal to treatment with laparoscopic surgery regarding success rate, complications, and subsequent fertility. Although the two treatment...

  7. A randomized, open-label study to investigate the effect of belimumab on pneumococcal vaccination in patients with active, autoantibody-positive systemic lupus erythematosus.

    Science.gov (United States)

    Chatham, W; Chadha, A; Fettiplace, J; Kleoudis, C; Bass, D; Roth, D; Gordon, D

    2017-12-01

    Objective Intravenous belimumab 10 mg/kg is approved as an add-on therapy in patients with active, autoantibody-positive systemic lupus erythematosus. This study aimed to assess the impact of belimumab on immune response to pneumococcal vaccination in patients with systemic lupus erythematosus. Methods This was a Phase 4, open-label study (GSK BEL115470; NCT01597492) conducted in the United States. Patients were randomized (7:9) to receive a 23-valent pneumococcal vaccination four weeks prior to (pre-belimumab cohort) or 24 weeks after (belimumab-concurrent cohort) commencing four-weekly belimumab 10 mg/kg intravenous treatment plus standard systemic lupus erythematosus therapy. Analyses of vaccine titers were performed on the as-treated population (received ≥1 dose of belimumab). The primary endpoint was the proportion of patients with positive antibody responses (≥2-fold increase from pre-vaccination levels, or post-vaccination level ≥ 0.6 µg/mL if pre-vaccination levels were unquantifiable) to ≥1 of 23 pneumococcal vaccine serotypes, four weeks post vaccination. Other endpoints included the proportion of patients with positive antibody responses to ≥2 to ≥10, and ≥11-23 (post hoc analysis) of serotypes. Safety was assessed by monitoring adverse events. Results Seventy-nine patients received pneumococcal vaccination (pre-belimumab cohort, n = 34; belimumab-concurrent cohort, n = 45). The majority (87.3% [69/79]) completed the study; 10 (12.7%) withdrew (patient request, n = 3; adverse event, n = 3; lost to follow-up, n = 2; other, n = 2). At Week 4 post-vaccination, 97.0% (32/33) and 97.6% (40/41) of patients (pre-belimumab and concurrent belimumab cohorts, respectively) had a positive response to ≥1 of 23 pneumococcal serotypes. Over 85% of patients in both cohorts responded to ≥10 of serotypes, approximately 80% responded to ≥12 serotypes, and approximately two-thirds responded to ≥16 serotypes. Little

  8. Shelf Life of Food Products: From Open Labeling to Real-Time Measurements.

    Science.gov (United States)

    Corradini, Maria G

    2018-03-25

    The labels currently used on food and beverage products only provide consumers with a rough guide to their expected shelf lives because they assume that a product only experiences a limited range of predefined handling and storage conditions. These static labels do not take into consideration conditions that might shorten a product's shelf life (such as temperature abuse), which can lead to problems associated with food safety and waste. Advances in shelf-life estimation have the potential to improve the safety, reliability, and sustainability of the food supply. Selection of appropriate kinetic models and data-analysis techniques is essential to predict shelf life, to account for variability in environmental conditions, and to allow real-time monitoring. Novel analytical tools to determine safety and quality attributes in situ coupled with modern tracking technologies and appropriate predictive tools have the potential to provide accurate estimations of the remaining shelf life of a food product in real time. This review summarizes the necessary steps to attain a transition from open labeling to real-time shelf-life measurements.

  9. The Efficacy of Single-Dose versus Double-Dose Praziquantel Treatments on Schistosoma mansoni Infections: Its Implication on Undernutrition and Anaemia among Primary Schoolchildren in Two On-Shore Communities, Northwestern Tanzania

    Science.gov (United States)

    Buza, Joram; Mpolya, Emmanuel A.; Angelo, Teckla; Kinung'hi, Safari M.

    2017-01-01

    Administering more than one treatment may increase Praziquantel cure and egg reduction rates, thereby hastening achievement of schistosomiasis transmission control. A total of 431 S. mansoni-infected schoolchildren were randomized to receive either a single or repeated 40 mg/kg Praziquantel dose. Heights, weights, and haemoglobin levels were determined using a stadiometer, weighing scale, and HemoCue, respectively. At 8 weeks, cure rate was higher on repeated dose (93.10%) compared to single dose (68.68%) (p 0.05) and 8 (p > 0.05) months with no difference in reinfection rate. No difference in the prevalence of stunting was observed between the two treatment regimens (p > 0.05) at 8 months, but there was an increase in the prevalence of wasting among those on repeated dose (p 0.05). To achieve reduction of transmission intensity and disease control in highly endemic areas, repeated treatments alone may not be sufficient. This trial was registered with PACTR201601001416338. PMID:29094048

  10. A phase II open label trial evaluating safety and efficacy of a telomerase peptide vaccination in patients with advanced hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Greten, Tim F; Bruix, Jordi; Forner, Alejandro; Korangy, Firouzeh; N'Kontchou, Gisele; Barget, Nathalie; Ayuso, Carmen; Ormandy, Lars A; Manns, Michael P; Beaugrand, Michel

    2010-01-01

    The sole effective option for patients with advanced HCC is sorafenib and there is an urgent need to develop new therapeutic approaches. Immunotherapy is a promising option that deserves major investigation. In this open label, single arm clinical trial, we analyzed the effect of a low dose cyclophosphamide treatment in combination with a telomerase peptide (GV1001) vaccination in patients with advanced HCC. 40 patients with advanced HCC were treated with 300 mg/m 2 cyclophosphamide on day -3 followed by GM-CSF + GV1001 vaccinations on days 1, 3, 5, 8, 15, 22, 36 followed by 4-weekly injections. Primary endpoint of this phase II trial was tumor response; secondary endpoints evaluated were TTP, TTSP, PFS, OS, safety and immune responses. None of the patients had a complete or partial response to treatment, 17 patients (45.9%) demonstrated a stable disease six months after initiation of treatment. The median TTP was 57.0 days; the median TTSP was estimated to be 358.0 days. Cyclophosphamide, GV1001 and GM-CSF treatment were well tolerated and most adverse events, which were of grade 1 or 2, were generally related to the injection procedure and injection site reactions. GV1001 treatment resulted in a decrease in CD4 + CD25 + Foxp3 + regulatory T cells; however, no GV1001 specific immune responses were detected after vaccination. Low dose cyclophosphamide treatment followed by GV1001 vaccinations did not show antitumor efficacy as per tumor response and time to progression. Further studies are needed to analyze the effect of a combined chemo-immunotherapy to treat patients with HCC. NCT00444782

  11. A phase II open label trial evaluating safety and efficacy of a telomerase peptide vaccination in patients with advanced hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Ayuso Carmen

    2010-05-01

    Full Text Available Abstract Background The sole effective option for patients with advanced HCC is sorafenib and there is an urgent need to develop new therapeutic approaches. Immunotherapy is a promising option that deserves major investigation. In this open label, single arm clinical trial, we analyzed the effect of a low dose cyclophosphamide treatment in combination with a telomerase peptide (GV1001 vaccination in patients with advanced HCC. Methods 40 patients with advanced HCC were treated with 300 mg/m2 cyclophosphamide on day -3 followed by GM-CSF + GV1001 vaccinations on days 1, 3, 5, 8, 15, 22, 36 followed by 4-weekly injections. Primary endpoint of this phase II trial was tumor response; secondary endpoints evaluated were TTP, TTSP, PFS, OS, safety and immune responses. Results None of the patients had a complete or partial response to treatment, 17 patients (45.9% demonstrated a stable disease six months after initiation of treatment. The median TTP was 57.0 days; the median TTSP was estimated to be 358.0 days. Cyclophosphamide, GV1001 and GM-CSF treatment were well tolerated and most adverse events, which were of grade 1 or 2, were generally related to the injection procedure and injection site reactions. GV1001 treatment resulted in a decrease in CD4+CD25+Foxp3+ regulatory T cells; however, no GV1001 specific immune responses were detected after vaccination. Conclusions Low dose cyclophosphamide treatment followed by GV1001 vaccinations did not show antitumor efficacy as per tumor response and time to progression. Further studies are needed to analyze the effect of a combined chemo-immunotherapy to treat patients with HCC. Trial registration NCT00444782

  12. Methods of a large prospective, randomised, open-label, blinded end-point study comparing morning versus evening dosing in hypertensive patients: the Treatment In Morning versus Evening (TIME) study.

    Science.gov (United States)

    Rorie, David A; Rogers, Amy; Mackenzie, Isla S; Ford, Ian; Webb, David J; Willams, Bryan; Brown, Morris; Poulter, Neil; Findlay, Evelyn; Saywood, Wendy; MacDonald, Thomas M

    2016-02-09

    Nocturnal blood pressure (BP) appears to be a better predictor of cardiovascular outcome than daytime BP. The BP lowering effects of most antihypertensive therapies are often greater in the first 12 h compared to the next 12 h. The Treatment In Morning versus Evening (TIME) study aims to establish whether evening dosing is more cardioprotective than morning dosing. The TIME study uses the prospective, randomised, open-label, blinded end-point (PROBE) design. TIME recruits participants by advertising in the community, from primary and secondary care, and from databases of consented patients in the UK. Participants must be aged over 18 years, prescribed at least one antihypertensive drug taken once a day, and have a valid email address. After the participants have self-enrolled and consented on the secure TIME website (http://www.timestudy.co.uk) they are randomised to take their antihypertensive medication in the morning or the evening. Participant follow-ups are conducted after 1 month and then every 3 months by automated email. The trial is expected to run for 5 years, randomising 10,269 participants, with average participant follow-up being 4 years. The primary end point is hospitalisation for the composite end point of non-fatal myocardial infarction (MI), non-fatal stroke (cerebrovascular accident; CVA) or any vascular death determined by record-linkage. Secondary end points are: each component of the primary end point, hospitalisation for non-fatal stroke, hospitalisation for non-fatal MI, cardiovascular death, all-cause mortality, hospitalisation or death from congestive heart failure. The primary outcome will be a comparison of time to first event comparing morning versus evening dosing using an intention-to-treat analysis. The sample size is calculated for a two-sided test to detect 20% superiority at 80% power. TIME has ethical approval in the UK, and results will be published in a peer-reviewed journal. UKCRN17071; Pre-results. Published by the BMJ

  13. Electroconvulsive therapy for the treatment of clozapine nonresponders suffering from schizophrenia--an open label study

    NARCIS (Netherlands)

    Kho, K. H.; Blansjaar, B. A.; de Vries, S.; Babuskova, D.; Zwinderman, A. H.; Linszen, D. H.

    2004-01-01

    OBJECTIVE: This open label study describes the efficacy of electroconvulsive therapy (ECT) as adjunctive treatment in clozapine nonresponders suffering from schizophrenia. METHOD: The results of clozapine and ECT treatment in 11 clozapine nonresponders suffering from schizophrenia are reported in

  14. Stochastic perturbations in open chaotic systems: random versus noisy maps.

    Science.gov (United States)

    Bódai, Tamás; Altmann, Eduardo G; Endler, Antonio

    2013-04-01

    We investigate the effects of random perturbations on fully chaotic open systems. Perturbations can be applied to each trajectory independently (white noise) or simultaneously to all trajectories (random map). We compare these two scenarios by generalizing the theory of open chaotic systems and introducing a time-dependent conditionally-map-invariant measure. For the same perturbation strength we show that the escape rate of the random map is always larger than that of the noisy map. In random maps we show that the escape rate κ and dimensions D of the relevant fractal sets often depend nonmonotonically on the intensity of the random perturbation. We discuss the accuracy (bias) and precision (variance) of finite-size estimators of κ and D, and show that the improvement of the precision of the estimations with the number of trajectories N is extremely slow ([proportionality]1/lnN). We also argue that the finite-size D estimators are typically biased. General theoretical results are combined with analytical calculations and numerical simulations in area-preserving baker maps.

  15. Safety and immune response to a challenge dose of hepatitis B vaccine in healthy children primed 10years earlier with hexavalent vaccines in a 3, 5, 11-month schedule: An open-label, controlled, multicentre trial in Italy.

    Science.gov (United States)

    Zanetti, Alessandro; Desole, Maria Giuseppina; Romanò, Luisa; d'Alessandro, Antonio; Conversano, Michele; Ferrera, Giuseppe; Panico, Maria Grazia; Tomasi, Alberto; Zoppi, Giorgio; Zuliani, Massimo; Thomas, Stéphane; Soubeyrand, Benoît; Eymin, Cécile; Lockhart, Stephen

    2017-07-13

    The strategy of vaccinating infants to prevent hepatitis B virus infection in adolescence or adulthood requires durable immunity. This study investigated responses to a challenge dose of monovalent hepatitis B vaccine in children primed with three doses of either Hexavac® or Infanrix hexa® 10years earlier during infancy. This open-label, controlled, multicentre study conducted in Italy, enrolled 751 healthy pre-adolescents (aged 11-13years) who were given either Hexavac (n=409) or Infanrix hexa (n=342) at 3, 5 and 11months of life. All participants received a challenge dose of a monovalent hepatitis B vaccine (HBVaxPro® 5µg). The concentrations of antibodies to hepatitis B surface antigen (anti-HBs) were measured before and 1month after the challenge dose. The analysis was descriptive and no formal hypothesis was tested. One month post-challenge, 331 participants in the Hexavac cohort [83.6%, 95% CI: 79.6; 87.1] and 324 in the Infanrix hexa cohort [96.4%, 95% CI: 93.8; 98.1] had anti-HBs concentrations ≥10mIU/mL. Before the challenge dose, an anti-HBs concentration of ≥10mIU/mL was found in 94 children in the Hexavac cohort [23.9%, 95% CI: 19.7; 28.4] and in 232 children in the Infanrix hexa cohort [69%, 95% CI: 63.8; 74.0]. Among children with a pre-challenge anti-HBs concentration of children (>80%) at least 10years after a two-dose primary and booster vaccination schedule with a hexavalent vaccine (Hexavac or Infanrix hexa). EudraCT Number: 2013-001602-28; clinicaltrials.gov: NCT02012998. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Lansoprazole for secondary prevention of gastric or duodenal ulcers associated with long-term low-dose aspirin therapy: results of a prospective, multicenter, double-blind, randomized, double-dummy, active-controlled trial.

    Science.gov (United States)

    Sugano, Kentaro; Matsumoto, Yasushi; Itabashi, Tsukasa; Abe, Sumihisa; Sakaki, Nobuhiro; Ashida, Kiyoshi; Mizokami, Yuji; Chiba, Tsutomu; Matsui, Shigeyuki; Kanto, Tatsuya; Shimada, Kazuyuki; Uchiyama, Shinichiro; Uemura, Naomi; Hiramatsu, Naoki

    2011-06-01

    The efficacy of low-dose lansoprazole has not been established for the prevention of recurrent gastric or duodenal ulcers in those receiving long-term low-dose aspirin (LDA) for cardiovascular and cerebrovascular protection. This study sought to examine the efficacy of low-dose lansoprazole (15 mg once daily) for the secondary prevention of LDA-associated gastric or duodenal ulcers. Patients were randomized to receive lansoprazole 15 mg daily (n = 226) or gefarnate 50 mg twice daily (n = 235) for 12 months or longer in a prospective, multicenter, double-blind, randomized active-controlled trial, followed by a 6-month follow-up study with open-label lansoprazole treatment. The study utilized 94 sites in Japan and 461 Japanese patients with a history of gastric or duodenal ulcers who required long-term LDA therapy for cardiovascular and cerebrovascular disease. The primary endpoint was the development of gastric or duodenal ulcers. The cumulative incidence of gastric or duodenal ulcers on days 91, 181, and 361 from the start of the study was calculated by the Kaplan-Meier method as 1.5, 2.1, and 3.7%, respectively, in the lansoprazole group versus 15.2, 24.0, and 31.7%, respectively, in the gefarnate group. The risk of ulcer development was significantly (log-rank test, P lansoprazole group than in the gefarnate group, with the hazard ratio being 0.099 (95% confidence interval [CI] 0.042-0.230). Lansoprazole was superior to gefarnate in reducing the risk of gastric or duodenal ulcer recurrence in patients with a definite history of gastric or duodenal ulcers who required long-term LDA therapy.

  17. Randomized clinical trial of laparoscopic versus open appendicectomy

    DEFF Research Database (Denmark)

    Pedersen, A G; Petersen, O B; Wara, P

    2001-01-01

    BACKGROUND: Laparoscopy in patients with a clinical suspicion of acute appendicitis has not gained wide acceptance, and its use remains controversial. METHODS: In a randomized controlled trial of laparoscopic versus open appendicectomy, 583 of 828 consecutive patients consented to participate...

  18. Ibuprofen plus paracetamol versus ibuprofen in acute low back pain: a randomized open label multicenter clinical study.

    Science.gov (United States)

    Ostojic, Predrag; Radunovic, Goran; Lazovic, Milica; Tomanovic-Vujadinovic, Sanja

    2017-01-01

    to estimate whether combination of ibuprofen and paracetamol is more effective than ibuprofen in monotherapy, in the treatment of acute low back pain. 80 adult patients with acute low back pain were randomized into two subgroups. In the first subgroup, 40 patients were treated with ibuprofen 400mg three times a day (TID), whilst patients in the second subgroup (n=40) were treated with a fixed-dose combination tablet of ibuprofen 200mg plus paracetamol 325mg TID, for three consecutive days. Patients were followed for another 7 days. Efficacy and tolerability of both treatment options was assessed. A statistically significant decrease in pain intensity, assessed using a visual analogue scale (pibuprofen monotherapy reported minor gastric intolerability. compared to ibuprofen monotherapy, combination of ibuprofen and paracetamol may provide faster and longer analgesia in patients with acute low back pain, with equally favorable effect on mobility and functional ability and similar tolerability.

  19. Comparison of tamsulosin plus serenoa repens with tamsulosin in the treatment of benign prostatic hyperplasia in Korean men: 1-year randomized open label study.

    Science.gov (United States)

    Ryu, Young Woo; Lim, Song Won; Kim, Jung Hoon; Ahn, Seung Hyun; Choi, Jae Duck

    2015-01-01

    In Korea, increasing attention has recently been given to the use of phytotherapeutic agents to alleviate the symptoms of BPH. Serenoa repens has been shown to have an equivalent efficacy to Finasteride or Tamsulosin in the treatment of BPH in previous studies. The present study was designed to compare the efficacy and safety of Serenoa repens plus tamsulosin with tamsulosin only over 12 months in men with LUTS secondary to BPH. One hundred forty men with symptomatic BPH (IPSS≥10) were recruited in our hospital for a 12-month, open-label, randomized trial. Patients were randomly assigned to either tamsulosin 0.2 mg/day plus Serenoa repens 320 mg/day (n=60) or tamsulosin 0.2 mg/day only (n=60). Prostate volume and PSA were measured at baseline and at end-point, whereas total IPSS, and its storage and voiding subscores, LUTS-related QoL, Qmax, and PVR were evaluated at baseline and later every 6 months. Total 103 patients were finally available: 50 in the TAM+SR group and 53 in the TAM group. At 12 months, total IPSS decreased by 5.8 with TAM+SR and 5.5 with TAM (p=0.693); the storage symptoms improved significantly more with TAM+SR (-1.7 vs. -0.8 with TAM, p=0.024). This benefit with regard to storage symptom in the TAM+SR group lasts at 12 months (-1.9 vs. -0.9, p=0.024). The changes of voiding subscore, LUTS-related QoL, Qmax, PVR, PSA, and prostate volume showed no significant differences between the TAM+SR and TAM groups. During the treatment period, 8 patients (16.9%) with TAM and 10 (20%) with TAM+SR had drug-related adverse reactions, which included ejaculatory disorders, postural hypotension, dizziness, headache, gastro-intestinal disorders, rhinitis, fatigue and asthenia. The combination treatment of Serenoa repens and tamsulosin was shown to be more effective than tamsulosin monotherapy in reducing storage symptoms in BPH patients after 6 months and up to 12 months of treatment. © 2015 S. Karger AG, Basel.

  20. Effect of single oral dose of tramadol on gastric secretions pH

    Directory of Open Access Journals (Sweden)

    Khan Mueen Ullah

    2015-01-01

    Full Text Available Background: Tramadol is an atypical analgesic agent. It has been shown that intramuscular or intravenous injection tramadol is able to inhibit M3 muscarinic receptors. Tramadol is able to mediate smooth muscles contraction and glandular secretions. We have evaluated the effects of single oral dose of tramadol given preoperatively on gastric juices pH in patients electively scheduled for laparoscopic cholecystectomy. Materials and Methods: Sixty adult, American Society of Anesthesiologist I and II patients scheduled for laparoscopic cholecystectomy were included in the study. Patients were randomly assigned to receive either placebo (n = 30 or oral tramadol 50 mg (n = 30. General anesthesia was induced using propofol, fentanyl and cisatracurium. After induction of anesthesia 5 ml of gastric fluid was aspirated through orogastric tube. The gastric fluid pH was measured using pH meter. Result: There was no significant difference in the pH between the groups. Gastric pH of the placebo and tramadol groups was 1.97 versus 1.98 (P = 0.092 respectively. Conclusion: Preoperatively single oral dose of tramadol was unable to elevate the desired level of gastric acid secretions pH (>2.5. This may be due to pharmacokinetic disparity between the analgesic and pH elevating properties of tramadol.

  1. Antimalarial activity of artefenomel (OZ439), a novel synthetic antimalarial endoperoxide, in patients with Plasmodium falciparum and Plasmodium vivax malaria: an open-label phase 2 trial.

    Science.gov (United States)

    Phyo, Aung Pyae; Jittamala, Podjanee; Nosten, François H; Pukrittayakamee, Sasithon; Imwong, Mallika; White, Nicholas J; Duparc, Stephan; Macintyre, Fiona; Baker, Mark; Möhrle, Jörg J

    2016-01-01

    Artefenomel (OZ439) is a novel synthetic trioxolane with improved pharmacokinetic properties compared with other antimalarial drugs with the artemisinin pharmacophore. Artefenomel has been generally well tolerated in volunteers at doses up to 1600 mg and is being developed as a partner drug in an antimalarial combination treatment. We investigated the efficacy, tolerability, and pharmacokinetics of artefenomel at different doses in patients with Plasmodium falciparum or Plasmodium vivax malaria. This phase 2a exploratory, open-label trial was done at the Hospital for Tropical Diseases, Bangkok, and the Shoklo Malaria Research Unit in Thailand. Adult patients with acute, uncomplicated P falciparum or P vivax malaria received artefenomel in a single oral dose (200 mg, 400 mg, 800 mg, or 1200 mg). The first cohort received 800 mg. Testing of a new dose of artefenomel in a patient cohort was decided on after safety and efficacy assessment of the preceding cohort. The primary endpoint was the natural log parasite reduction per 24 h. Definitive oral treatment was given at 36 h. This trial is registered with ClinicalTrials.gov, number NCT01213966. Between Oct 24, 2010, and May 25, 2012, 82 patients were enrolled (20 in each of the 200 mg, 400 mg, and 800 mg cohorts, and 21 in the 1200 mg cohort). One patient withdrew consent (before the administration of artefenomel) but there were no further dropouts. The parasite reduction rates per 24 h ranged from 0·90 to 1·88 for P falciparum, and 2·09 to 2·53 for P vivax. All doses were equally effective in both P falciparum and P vivax malaria, with median parasite clearance half-lives of 4·1 h (range 1·3-6·7) to 5·6 h (2·0-8·5) for P falciparum and 2·3 h (1·2-3·9) to 3·2 h (0·9-15·0) for P vivax. Maximum plasma concentrations, dose-proportional to 800 mg, occurred at 4 h (median). The estimated elimination half-life was 46-62 h. No serious drug-related adverse effects were reported; other adverse effects were

  2. A Prospective Study Comparing Ligasure and Open Hemorrhoidectomy

    Directory of Open Access Journals (Sweden)

    Rahimi M

    2011-11-01

    Full Text Available Background: Hemorrhoid is among the most common anorectal diseases and patients with high-grade disease conditions need surgical treatment. Many surgical procedures are available to treat the disease. The aim of this study was to compare the operative time and outcomes, (post-operative pain and complications of LigaSure hemorrhoidectomy with those of the open conventional method.Methods : This randomized single-blind clinical trial included 57 patients (28 in LigaSure and 29 in the open group. The primary variable was the operative time for the excision of a single hemorrhoidal packet. The other variables were post-operative pain measured by morphine doses administered to control pain, scores of visual analogue scale (VAS used to measure pain severity, pain during home stay measured by doses of oral ibuprofen and the mean daily VAS scores, early complications including bleeding and urinary retention, longer-term complications and time to return to work.Results : The demographic data were comparatively the same between the two groups. The average time to excise a single packet of hemorrhoid was significantly shorter in the LigaSure group (8.91 min vs. 17.35 min, P<0.001. Post-operative pain measurements (morphine doses and VAS scores were lower in the LigaSure group, but the differences were not statistically significant (P=0.055 and 0.077, respectively. Complications of the two procedures were also comparable. Neither of the groups returned to work in a shorter time.Conclusion: LigaSure hemorrhoidectomy seems to be a safe method and it can reduce the operative time significantly. It may also have a modest effect on post-operative pain.

  3. Local Heat Application for the Treatment of Buruli Ulcer: Results of a Phase II Open Label Single Center Non Comparative Clinical Trial.

    Science.gov (United States)

    Vogel, Moritz; Bayi, Pierre F; Ruf, Marie-Thérèse; Bratschi, Martin W; Bolz, Miriam; Um Boock, Alphonse; Zwahlen, Marcel; Pluschke, Gerd; Junghanss, Thomas

    2016-02-01

    Buruli ulcer (BU) is a necrotizing skin disease most prevalent among West African children. The causative organism, Mycobacterium ulcerans, is sensitive to temperatures above 37°C. We investigated the safety and efficacy of a local heat application device based on phase change material. In a phase II open label single center noncomparative clinical trial (ISRCTN 72102977) under GCP standards in Cameroon, laboratory confirmed BU patients received up to 8 weeks of heat treatment. We assessed efficacy based on the endpoints 'absence of clinical BU specific features' or 'wound closure' within 6 months ("primary cure"), and 'absence of clinical recurrence within 24 month' ("definite cure"). Of 53 patients 51 (96%) had ulcerative disease. 62% were classified as World Health Organization category II, 19% each as category I and III. The average lesion size was 45 cm(2). Within 6 months after completion of heat treatment 92.4% (49 of 53, 95% confidence interval [CI], 81.8% to 98.0%) achieved cure of their primary lesion. At 24 months follow-up 83.7% (41 of 49, 95% CI, 70.3% to 92.7%) of patients with primary cure remained free of recurrence. Heat treatment was well tolerated; adverse effects were occasional mild local skin reactions. Local thermotherapy is a highly effective, simple, cheap and safe treatment for M. ulcerans disease. It has in particular potential as home-based remedy for BU suspicious lesions at community level where laboratory confirmation is not available. ISRCT 72102977. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America.

  4. Evaluation of the sterility of single-dose medications used in a multiple-dose fashion.

    Science.gov (United States)

    Martin, Elizabeth P; Mukherjee, Jean; Sharp, Claire R; Sinnott-Stutzman, Virginia B

    2017-11-01

    Bacterial proliferation was evaluated in single-dose medications used in a multi-dose fashion and when medications were intentionally inoculated with bacteria. Of 5 experimentally punctured medications, 1 of 75 vials (50% dextrose) became contaminated. When intentionally inoculated, hydroxyethyl starch and heparinized saline supported microbial growth. Based on these findings, it is recommended that hydroxyethyl starch and heparinized saline not be used in a multi-dose fashion.

  5. Mechanics of single-walled carbon nanotubes inside open single-walled carbon nanocones

    International Nuclear Information System (INIS)

    Ansari, R.; Hosseinzadeh, M.

    2013-01-01

    This study investigates the mechanical characteristics of single-walled carbon nanotubes (CNTs) inside open single-walled carbon nanocones (CNCs). New semi-analytical expressions are presented to evaluate van der Waals (vdW) interactions between CNTs and open CNCs. Continuum approximation, along with the the Lennard-Jones (LJ) potential function, is used in this study. The effects of geometrical parameters on alterations in vdW potential energy and the interaction force are extensively examined for the concentric CNT-open CNC configuration. The CNT is assumed to enter the nanocone either through the small end or the wide end of the cone. The preferred position of the CNT with respect to the nanocone axis is fully investigated for various geometrical parameters. The optimum nanotube radius minimizing the total potential energy of the concentric configuration is determined for different radii of the small end of the cone. The examined configuration generates asymmetric oscillation; thus, the system constitutes a nano-oscillator.

  6. Pharmacokinetics and Safety of a Single Oral Dose of Mirogabalin in Japanese Subjects With Varying Degrees of Renal Impairment.

    Science.gov (United States)

    Kato, Manabu; Tajima, Naoyuki; Shimizu, Takako; Sugihara, Masahiro; Furihata, Kenichi; Harada, Kazuhiro; Ishizuka, Hitoshi

    2018-01-01

    Mirogabalin (DS-5565) is a novel preferentially selective α 2 δ-1 ligand being developed for the treatment of diabetic peripheral neuropathic pain and postherpetic neuralgia. The current multicenter open-label study determined the effect of varying degrees of renal impairment on the pharmacokinetics and safety of a single dose of mirogabalin 5 mg in Japanese subjects. A total of 30 subjects (6 subjects per renal function category [normal, mild, moderate, or severe impairment; and end-stage renal disease (ESRD)]) were enrolled and completed the study. The AUC last increased with severity of renal impairment; the geometric least-squares mean ratios of AUC last compared with subjects with normal renal function were 1.3, 1.9, 3.6, and 5.3 for patients with mild, moderate, and severe impairment and ESRD, respectively. In accordance with this AUC last increase, apparent total body clearance (CL/F), renal clearance (CLr), and the cumulative percentage of mirogabalin dose excreted into urine all decreased with severity of renal impairment. There were no deaths and no severe treatment-related adverse events (TEAEs), serious TEAEs, or TEAEs resulting in study discontinuation. Mirogabalin was well tolerated in Japanese subjects with normal renal function and those with mild to severe renal impairment. It was also tolerated in subjects with ESRD but with a higher incidence of TEAEs. The most frequently reported TEAEs were dizziness (ESRD, n = 3), somnolence (ESRD, n = 2), and vomiting (ESRD, n = 2). Based on these data, a mirogabalin dose adjustment will be considered in Japanese subjects with moderate to severe renal impairment and those with ESRD. © 2017, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

  7. First-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance therapy for patients with advanced EGFR mutation-positive lung adenocarcinoma (CONVINCE): a phase 3, open-label, randomized study.

    Science.gov (United States)

    Shi, Y K; Wang, L; Han, B H; Li, W; Yu, P; Liu, Y P; Ding, C M; Song, X; Ma, Z Y; Ren, X L; Feng, J F; Zhang, H L; Chen, G Y; Han, X H; Wu, N; Yao, C; Song, Y; Zhang, S C; Song, W; Liu, X Q; Zhao, S J; Lin, Y C; Ye, X Q; Li, K; Shu, Y Q; Ding, L M; Tan, F L; Sun, Y

    2017-10-01

    Icotinib has been previously shown to be non-inferior to gefitinib in non-selected advanced non-small-cell lung cancer patients when given as second- or further-line treatment. In this open-label, randomized, phase 3 CONVINCE trial, we assessed the efficacy and safety of first-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance in lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) mutation. Eligible participants were adults with stage IIIB/IV lung adenocarcinoma and exon 19/21 EGFR mutations. Participants were randomly allocated (1 : 1) to receive oral icotinib or 3-week cycle of cisplatin plus pemetrexed for up to four cycles; non-progressive patients after four cycles were maintained with pemetrexed until disease progression or intolerable toxicity. The primary end point was progression-free survival (PFS) assessed by independent response evaluation committee. Other end points included overall survival (OS) and safety. Between January 2013 and August 2014, 296 patients were randomized, and 285 patients were treated (148 to icotinib, 137 to chemotherapy). Independent response evaluation committee-assessed PFS was significantly longer in the icotinib group (11.2 versus 7.9 months; hazard ratio, 0.61, 95% confidence interval 0.43-0.87; P = 0.006). No significant difference for OS was observed between treatments in the overall population or in EGFR-mutated subgroups (exon 19 Del/21 L858R). The most common grade 3 or 4 adverse events (AEs) in the icotinib group were rash (14.8%) and diarrhea (7.4%), compared with nausea (45.9%), vomiting (29.2%), and neutropenia (10.9%) in the chemotherapy group. AEs (79.1% versus 94.2%; P icotinib group than in the chemotherapy group. First-line icotinib significantly improves PFS of advanced lung adenocarcinoma patients with EGFR mutation with a tolerable and manageable safety profile. Icotinib should be considered as a first-line treatment for this patient population. © The Author

  8. A phase I open-label dose-escalation study of the anti-HER3 monoclonal antibody LJM716 in patients with advanced squamous cell carcinoma of the esophagus or head and neck and HER2-overexpressing breast or gastric cancer.

    Science.gov (United States)

    Reynolds, Kerry Lynn; Bedard, Philippe L; Lee, Se-Hoon; Lin, Chia-Chi; Tabernero, Josep; Alsina, Maria; Cohen, Ezra; Baselga, José; Blumenschein, George; Graham, Donna M; Garrido-Laguna, Ignacio; Juric, Dejan; Sharma, Sunil; Salgia, Ravi; Seroutou, Abdelkader; Tian, Xianbin; Fernandez, Rose; Morozov, Alex; Sheng, Qing; Ramkumar, Thiruvamoor; Zubel, Angela; Bang, Yung-Jue

    2017-09-12

    Human epidermal growth factor receptor 3 (HER3) is important in maintaining epidermal growth factor receptor-driven cancers and mediating resistance to targeted therapy. A phase I study of anti-HER3 monoclonal antibody LJM716 was conducted with the primary objective to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE), and dosing schedule. Secondary objectives were to characterize safety/tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity. This open-label, dose-finding study comprised dose escalation, followed by expansion in patients with squamous cell carcinoma of the head and neck or esophagus, and HER2-overexpressing metastatic breast cancer or gastric cancer. During dose escalation, patients received LJM716 intravenous once weekly (QW) or every two weeks (Q2W), in 28-day cycles. An adaptive Bayesian logistic regression model was used to guide dose escalation and establish the RDE. Exploratory pharmacodynamic tumor studies evaluated modulation of HER3 signaling. Patients received LJM716 3-40 mg/kg QW and 20 mg/kg Q2W (54 patients; 36 patients at 40 mg/kg QW). No dose-limiting toxicities (DLTs) were reported during dose-escalation. One patient experienced two DLTs (diarrhea, hypokalemia [both grade 3]) in the expansion phase. The RDE was 40 mg/kg QW, providing drug levels above the preclinical minimum effective concentration. One patient with gastric cancer had an unconfirmed partial response; 17/54 patients had stable disease, two lasting >30 weeks. Down-modulation of phospho-HER3 was observed in paired tumor samples. LJM716 was well tolerated; the MTD was not reached, and the RDE was 40 mg/kg QW. Further development of LJM716 is ongoing. Clinicaltrials.gov registry number NCT01598077 (registered on 4 May, 2012).

  9. Microdose study of a P-glycoprotein substrate, fexofenadine, using a non-radioisotope-labelled drug and LC/MS/MS.

    Science.gov (United States)

    Yamazaki, A; Kumagai, Y; Yamane, N; Tozuka, Z; Sugiyama, Y; Fujita, T; Yokota, S; Maeda, M

    2010-04-01

    Fexofenadine is a P-glycoprotein substrate of low bioavailability. It is primarily excreted into faeces as a parent drug via biliary excretion. The predictability from microdose data for the drug absorbed via transporters such as P-glycoprotein is not known. Therefore, this study assessed the predictability of therapeutic-dose pharmacokinetics of fexofenadine from microdosing data using non-radioisotope-labelled drug and liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS). In a single dose, randomized, two-way crossover study, eight subjects received a microdose (100 microg) or a therapeutic dose (60 mg) of fexofenadine. Blood samples were collected until 12 h after dosing, and assayed using LC/MS/MS. Plasma concentration-time curves of fexofenadine between microdose and therapeutic dose were similar. The mean +/- SD of C(max) normalized to 60 mg dose after microdose and therapeutic dose were 379 +/- 147 and 275 +/- 145 ng/mL respectively. The mean AUC(last) normalized to 60 mg dose after microdose and therapeutic dose were 1914 +/- 738 and 1431 +/- 432 ng/h/mL respectively. The mean dose-adjusted C(max) and AUC(last) after microdose were higher compared with those after therapeutic dose. Individual plots of C(max) and AUC(last) normalized to 60 mg dose, were similar for microdose and therapeutic dose. None of the pharmacokinetic parameters were statistically different using anova. Overall, the microdose pharmacokinetics profile was similar to, and hence predictive of, that of the therapeutic dose. For the P-glycoprotein substrate fexofenadine, the predictability of therapeutic-dose pharmacokinetics from microdose data was good. A microdose study using a non-radioisotope-labelled drug and LC/MS/MS is convenient, and has the potential to aid the early selection of drug candidates.

  10. A phase III, open-label, single-arm study of tenecteplase for restoration of function in dysfunctional central venous catheters.

    Science.gov (United States)

    Tebbi, Cameron; Costanzi, John; Shulman, Robert; Dreisbach, Luke; Jacobs, Brian R; Blaney, Martha; Ashby, Mark; Gillespie, Barbara S; Begelman, Susan M

    2011-08-01

    To evaluate, in a phase III, single-arm study, the safety and efficacy of the thrombolytic agent tenecteplase in restoring function to dysfunctional central venous catheters (CVCs). Pediatric and adult patients with dysfunctional CVCs were eligible to receive as much as 2 mL (2 mg) of intraluminal tenecteplase, which was left to dwell in the CVC lumen for a maximum of 120 minutes. If CVC function was not restored at 120 minutes, a second dose was instilled for an additional 120 minutes. Tenecteplase was administered to 246 patients. Mean patient age was 44 years (range, 0-92 y); 72 patients (29%) were younger than 17 years of age. Chemotherapy was the most common reason for catheter insertion. Restoration of CVC function was achieved in 177 patients (72%) within 120 minutes after the first dose. After instillation of a maximum of two doses of tenecteplase, CVC function was restored in 200 patients (81%), with similar frequencies in pediatric (83%) and adult (80%) patients. Adverse events (AEs) were reported in 31 patients (13%); fever (2%), neutropenia (1%), and nausea (0.8%) were most common. One serious AE, an allergic hypersensitivity reaction, was judged to be related to tenecteplase and/or a chemotherapeutic agent that the patient was receiving concurrently. Consecutive administration of one or two doses of tenecteplase into CVCs showed efficacy in the restoration of catheter function in patients with dysfunctional CVCs. Copyright © 2011 SIR. Published by Elsevier Inc. All rights reserved.

  11. Single-dose-response curves of murine gastrointestinal crypt stem cells

    International Nuclear Information System (INIS)

    Masuda, K.; Withers, H.R.; Mason, K.A.; Chen, K.Y.

    1977-01-01

    Dose-response curves for the reproductive capacity of crypt stem cells of murine colonic, jejunal, and gastric mucosae exposed in situ to multifractionated gamma ray exposures were analyzed and single-dose-survival curves of these cells were constructed. The following conclusions were drawn: (1) The single-dose-response curves bend downward over a dose range of approximately 200 to 1500 rad; (2) cell death seems to be due to nonrepairable damage at doses less than 250 rad for colon, and 220 rad for jejunum; (3) there are 21, 110, and 140 stem cells per crypt of gastric, colonic, and jejunal mucosa, respectively; and (4) jejunal stem cells are the most radiosensitive and gastric mucosal stem cells are the most resistant

  12. INFLUENCE OF GRADED AEROBIC EXERCISE ON QUALITY OF LIFE IN POST SURGICAL MITRAL VALVE DISEASE INDIVIDUAL A PROSPECTIVE RANDOMIZED OPEN LABEL STUDY

    Directory of Open Access Journals (Sweden)

    Shanthi C

    2016-10-01

    Full Text Available Background: Post surgical mitral valve disease individual focus their cardiac rehabilitation training on two major goal that is to improve cardiac output response exercises and place an important role in determining exercise tolerance and to improve quality of life. Cardiac rehabilitation programs involve prescribed exercise and education however various other method are being used to improve quality of life. But our study to find out the effectiveness of graded aerobic exercise protocol on ejection fraction and quality of life in post surgical mitral valve disease individuals. Methods: The study design was open label studies total of 100 post surgical mitral valve disease individuals patients from the age group of 20-60 years were recruited from SVIMS hospital. They were randomly divided into two groups. Group I underwent a twelve week structured graded individually tailored exercises. The group II received only none graded (not individualized exercise training. The ejection fraction and quality of life was measured before and after 12 weeks of exercise training for two groups. Results: Repeated measures ANOVA was used to compare mean values of continuous variables between baseline and at the time of discharge and three months after surgery for each parameter. Comparison of means between groups was done by the unpaired student t test. Mean age of the subjects was 40.18±10.29. There was a significant increase in the ejection fraction in the group I(61.34±2.49 to 64.4±3.31 compared to with the group II (61.06±2.51. to 61.62 ±2.37. QOL had improved in group I than group II at p<0.05. Conclusion: A 12 week structured graded aerobic exercise training significantly improved ejection fraction and quality of life in post surgical mitral valve disease individuals.

  13. Melatonin for Sleep in Children with Autism: A Controlled Trial Examining Dose, Tolerability, and Outcomes

    Science.gov (United States)

    Malow, Beth; Adkins, Karen W.; McGrew, Susan G.; Wang, Lily; Goldman, Suzanne E.; Fawkes, Diane; Burnette, Courtney

    2012-01-01

    Supplemental melatonin has shown promise in treating sleep onset insomnia in children with autism spectrum disorders (ASD). Twenty-four children, free of psychotropic medications, completed an open-label dose-escalation study to assess dose-response, tolerability, safety, feasibility of collecting actigraphy data, and ability of outcome measures…

  14. Variation in Depth Dose Data between Open and Wedge Fields for 6 MV X-Rays

    International Nuclear Information System (INIS)

    U, Hong; Ryu, M. S. Samuel; Park, In Kyu

    1989-01-01

    Central axis depth dose data for 6 MV X-rays, including tissue maximum ratios, were measured for wedge fields according to Tatcher equation. In wedge fields, the differences in magnitude which increased with depth, field size, and wedge thickness increased when compared with the corresponding open field data. However, phantom scatter correction factors for wedge fields differed less that 1% from the corresponding open field factors. The differences in central axis percent depth dose between two types of fields indicated beam hardening by the wedge filter. The deviation of percent depth doses and scatter correction factors between the effective wedge field and the nominal wedge field at same angle was negligible. The differences were less than 3.26% between the nominal or effective wedge fields and the open fields for percent depth doses to the depth 7cm in 6cm x 6cm field. For larger (10cm x 10cm) field size, however, the deviation of percent depth doses between the nominal or effective wedge fields and the open fields were greater-dosimetric errors were 3.56% at depth 7cm and nearly 5.30% at 12cm. We suggest that the percent depth doses of individual wedge and wedge transmission factors should be considered for the dose calculation or monitor setting in the treatment of deep seated tumor

  15. Randomized controlled trial comparing different single doses of intravenous paracetamol for placement of peripherally inserted central catheters in preterm infants

    NARCIS (Netherlands)

    D.W.E. Roofthooft (Daniella); S.H. Simons (Sinno); R.A. Lingen (Richard); D. Tibboel (Dick); J.N. van den Anker (John); I.K.M. Reiss (Irwin); M. van Dijk (Monique)

    2017-01-01

    markdownabstract__Background:__ The availability of a safe and effective pharmacological therapy to reduce procedural pain in preterm infants is limited. The effective analgesic single dose of intravenous paracetamol in preterm infants is unknown. Comparative studies on efficacy of different

  16. Single-Agent Panitumumab in Frail Elderly Patients With Advanced RAS and BRAF Wild-Type Colorectal Cancer: Challenging Drug Label to Light Up New Hope

    Science.gov (United States)

    Cremolini, Chiara; Aprile, Giuseppe; Lonardi, Sara; Orlandi, Armando; Mennitto, Alessia; Berenato, Rosa; Antoniotti, Carlotta; Casagrande, Mariaelena; Marsico, Valentina; Marmorino, Federica; Cardellino, Giovanni Gerardo; Bergamo, Francesca; Tomasello, Gianluca; Formica, Vincenzo; Longarini, Raffaella; Giommoni, Elisa; Caporale, Marta; Di Bartolomeo, Maria; Loupakis, Fotios; de Braud, Filippo

    2015-01-01

    Background. No prospective trials have specifically addressed the efficacy and safety of panitumumab in elderly patients with metastatic colorectal cancer (CRC). We aimed at assessing the efficacy and safety of single agent panitumumab in “frail” elderly patients diagnosed with metastatic RAS and BRAF wild-type CRC. Materials and Methods. Forty elderly patients (aged ≥75 years) with metastatic RAS-BRAF wild-type CRC received off-label prescriptions of single-agent panitumumab at seven Italian institutions. Treatment was administered as first line in patients with absolute contraindication to any chemotherapy or as second-line treatment after failure of a fluoropyrimidine-based treatment, in the presence of contraindication to irinotecan. The outcome measures included objective response rate (ORR), as well as progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and safety. Results. The median PFS and OS were 6.4 months (95% confidence interval [CI]: 4.9–8 months) and 14.3 months (95% CI: 10.9–17.7 months), respectively. ORR was 32.5%, and DCR was 72.5%. Dose reductions related to adverse events (AEs) were reported in 9 (23%) patients, but no permanent treatment discontinuation caused by was reported. The most frequent grade 3 AE was skin rash, with an incidence of 20%. Conclusion. Panitumumab is effective and well-tolerated in frail elderly patients with RAS-BRAF wild-type metastatic CRC and deemed unfit for chemotherapy. A randomized study is needed to confirm these data. Implications for Practice: Treatment of elderly patients with metastatic colorectal cancer represents a difficult challenge in clinical practice. A significant proportion of frail elderly patients do not receive treatment, reflecting ongoing uncertainty of clinical benefit and toxicity of chemotherapy. Unfit condition in this cohort of patients further limits antineoplastic prescription and consequently patient survival. RAS and BRAF wild-type status could

  17. VANTAGE 095: An International, Multicenter, Open-Label Study of Vorinostat (MK-0683) in Combination With Bortezomib in Patients With Relapsed and Refractory Multiple Myeloma.

    Science.gov (United States)

    Siegel, David S; Dimopoulos, Meletios; Jagannath, Sundar; Goldschmidt, Hartmut; Durrant, Simon; Kaufman, Jonathan L; Leleu, Xavier; Nagler, Arnon; Offner, Fritz; Graef, Thorsten; Eid, Joseph E; Houp, Jennifer; Gause, Christine; Vuocolo, Scott; Anderson, Kenneth C

    2016-06-01

    The present global, open-label, single-arm, multicenter, phase IIb study was designed to determine the efficacy and tolerability of oral vorinostat combined with standard doses of bortezomib in patients with multiple myeloma considered refractory to novel myeloma agents. Eligible patients were age ≥ 18 years, had received ≥ 2 previous regimens, had disease refractory to ≥ 1 previous bortezomib-containing regimen, and had received ≥ 1 dose of an immunomodulatory drug (thalidomide or lenalidomide)-based regimen. The patients received 21-day cycles of bortezomib (1.3 mg/m(2) intravenously on days 1, 4, 8, and 11) plus oral vorinostat (400 mg/d on days 1-14). Oral dexamethasone, 20 mg, on the day of and the day after each dose of bortezomib could be added for patients with progressive disease after 2 cycles or no change after 4 cycles. The primary endpoint was the objective response rate. The objective response rate was 11.3% (95% confidence interval, 6.6%-17.7%), and the median duration of response was 211 days (range, 64-550 days). The median overall survival duration was 11.2 months (95% confidence interval, 8.5-14.4 months), with a 2-year survival rate of 32%. The frequently reported adverse events were thrombocytopenia (69.7%), nausea (57.0%), diarrhea (53.5%), anemia (52.1%), and fatigue (48.6%); the overall safety profile was consistent with that of bortezomib and vorinostat. The combination of vorinostat and bortezomib is active in patients with multiple myeloma refractory to novel treatment modalities and offers a new therapeutic option for this difficult-to-treat patient population (ClinicalTrials.gov identifier, NCT00773838). Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Is single-dose fosfomycin trometamol a good alternative for asymptomatic bacteriuria in the second trimesterof pregnancy?

    Science.gov (United States)

    Bayrak, Omer; Cimentepe, Ersin; Inegöl, Ilknur; Atmaca, Ali Fuat; Duvan, Candan Iltemir; Koç, Akif; Turhan, Nilgün Oztürk

    2007-05-01

    Untreated asymptomatic bacteriuria has been associated with acute pyelonephritis, which may have a role in many maternal and fetal complications. Acute pyelonephritis in pregnancy is related to anemia, septicemia, transient renal dysfunction, and pulmonary insufficiency. A randomized study was conducted to assess the clinical and microbiological efficacy of a single dose of fosfomycin trometamol for the treatment of asymptomatic bacteriuria in the second trimester of pregnancy compared with a 5-day regimen of cefuroxime axetyl. Forty-four women received fosfomycin trometamol and 40 women received cefuroxime axetyl. There were no statistically significant differences between both groups regarding the mean age and mean duration of pregnancy. Therapeutic success was achieved in 93.2% of the patients treated with fosfomycin trometamol vs 95% of those treated with cefuroxime axetyl. A single dose of fosfomycin trometamol is a safe and effective alternative in the treatment of asymptomatic urinary tract infections in the second trimester of pregnancy.

  19. A randomized open-label controlled trial of chlorhexidine-alcohol vs povidone-iodine for cesarean antisepsis: the CAPICA trial.

    Science.gov (United States)

    Springel, Edward H; Wang, Xiao-Yu; Sarfoh, Vanessa M; Stetzer, Bradley P; Weight, Steven A; Mercer, Brian M

    2017-10-01

    Identification of optimal surgical site antisepsis preparations may reduce cesarean-related surgical site infections. Two recently published investigations examined efficacy of chlorhexidine-alcohol and iodine-alcohol preparations. No previous randomized controlled trial has compared chlorhexidine-alcohol to povidone-iodine aqueous scrub and paint in reduction of cesarean-related surgical site infection. The purpose of the study was to determine if chlorhexidine-alcohol would result in fewer surgical site infections than povidone-iodine when used as skin antisepsis preparation prior to cesarean delivery. This study was a single-center pragmatic randomized controlled trial at an urban tertiary care institution to compare chlorhexidine-alcohol 26-mL single-step applicator to povidone-iodine aqueous scrub and paint 236-mL wet skin tray as preoperative skin antiseptic preparation for women undergoing cesarean delivery. Patients were eligible for study participation if they could provide informed consent in English or Spanish, were ≥18 years of age, did not have clinical chorioamnionitis, were unlikely to be lost to follow-up, and had no sensitivities to chlorhexidine, betadine, or iodine. Treatment was assigned by computer-generated simple 1:1 randomization immediately before skin preparation. The primary outcome was surgical site infection occurring within 30 days of cesarean delivery including ≥1 of: superficial or deep surgical site infection, or endometritis, according to Centers for Disease Control and Prevention definitions. Analysis was by intent to treat. Categorical outcomes were compared using Fisher exact test. The Wilcoxon rank-sum test was performed for continuous outcomes. This trial was institutional review board approved and registered at ClinicalTrials.gov (NCT02202577). In all, 932 subjects (461 assigned to chlorhexidine-alcohol, 471 assigned to povidone-iodine) were randomized from February 2013 through May 2016. Rate of follow-up evaluation

  20. HALF-DOSE DEPOT TRIPTORELIN COMPARABLE TO REDUCED DAILY BUSERELIN: A RANDOMIZED CLINICAL TRIAL

    Directory of Open Access Journals (Sweden)

    L. Safdarian

    2007-09-01

    Full Text Available Pituitary suppression by depot GnRH agonist may be excessive for ovarian stimulation. This study compares the efficacy of a single half-dose depot triptorelin and reduced-dose daily buserelin in a long protocol ICSI/ET. METHODS: A total of 182 patients were randomized into two groups using sealed envelopes. Pituitary desensitization was obtained in group 1 (91 patients with half-dose (1.87 mg depot triptorelin in the mid-luteal phase of their menstrual cycle, and in group 2 (91 patients with standard daily dose (0.5 mg buserelin, which was then reduced to 0.25 mg at the start of human menopausal gonadotropin (HMG stimulation. RESULTS: No significant differences were found among those who received HCG in terms of clinical pregnancy rate (34.4% in both groups, implantation rate (14.8% in group 1 versus 11.1% in group 2, fertilization rate (93.3 versus 95.6%, poor response rate (11.1 versus 6.7%, and miscarriage rate (11.1 versus 7.8%. No significant differences were seen in number of HMG ampoules used, follicles at HCG administration, and oocytes retrieved. The number of days of stimulation was significantly reduced in group 2 (11.2 +/- 1.8 in group 1 versus 10.6 +/- 1.9, p = 0.030. CONCLUSION: A half-dose of depot triptorelin can be successfully used in ovarian stimulation instead of reduced-dose daily buserelin, with more patient comfort and reduced stress and cost of injections.

  1. Effect of single-dose albendazole and vitamin A supplementation on the iron status of pre-school children in Sichuan, China.

    Science.gov (United States)

    Chen, Ke; Xie, Hu Mina; Tian, Weizheng; Zheng, Xiaoling; Jiang, Alice C

    2016-04-01

    The aim of this study was to explore the effect of single-dose albendazole and vitamin A intervention on the anaemic status and Fe metabolism of pre-school children. This study was a randomised, placebo-controlled and double-blinded intervention trial. All eligible anaemic pre-school children were randomly divided into three groups: group 1 received no intervention, which served as the control group, group 2 received 400 mg single-dose albendazole administration and group 3 received a 60000 μg vitamin A capsule combined with 400 mg single-dose albendazole at the beginning of the study. The follow-up period was for 6 months. Anthropometry and biochemical index about Fe metabolism were measured before and after intervention. A total of 209 pre-school anaemic children were randomly divided into three intervention groups (sixty-four, sixty-two and sixty for groups 1, 2 and 3, respectively). The mean age of the children in the study was 4·4 (sd 0·7) years and 50·5 % of the children were female (94/186). After a follow-up period of 6 months, the levels of serum retinol, ferritin, transferrin receptor-ferritin index and body total Fe content of children in group 3 were significantly higher compared with children in groups 1 and 2 (PAlbendazole plus vitamin A administration showed more efficacy on the improvement of serum retinol and Fe metabolic status.

  2. Prospective open randomized study comparing efficacies and safeties of a 3-day course of azithromycin and a 10-day course of erythromycin in children with community-acquired acute lower respiratory tract infections

    NARCIS (Netherlands)

    Roord, JJ; Goossens, MMHT; Kimpen, JLL; Wolf, B.H.

    1996-01-01

    The efficacies and safeties of a 3-day, 3-dose course of azithromycin (10 mg/kg of body weight per day) and a 10-day, 30-dose course of erythromycin (40 mg/kg/day) for the treatment of acute lower respiratory tract infections in children were compared in an open randomized multicenter study.

  3. Comparison of latanoprost with fixed-combination dorzolamide and timolol in adult patients with elevated intraocular pressure: an eight-week, randomized, open-label, parallel-group, multicenter study in Latin America.

    Science.gov (United States)

    Susanna, Remo; Sussana, Remo; Sheu, Wang-Pui

    2004-05-01

    The newer ocular hypotensive agents available to treat glaucoma and ocular hypertension (OHT) include latanoprost, a prostaglandin F(2alpha) analogue, and the fixed combination of dorzolamide hydrochloride, a carbonic anhydrase inhibitor, and timolol maleate, a beta-blocker. The aim of this study was to compare the efficacy and tolerability of latanoprost with that of the fixed combination of dorzolamide and timolol over 8 weeks. This interventional, 8-week, randomized, open-label, parallel-group study was conducted at 18 centers in 6 Latin American countries. Patients with unilateral or bilateral primary open-angle, pigmentary, or exfoliative glaucoma or OHT were randomized to receive latanoprost, 1 drop in the affected eye QD (evening), or fixed-combination dorzolamide/timolol, 1 drop in the affected eye BID (morning and evening). Medications were self-administered, 1 drop per affected eye. At baseline and week 8, intraocular pressure (IOP) was measured 3 times each at 8:30 am, 10:00 am, 2:00 pm, and 5:00 pm and after the water-drinking test, which estimates the IOP peak of diurnal tension curve, performed following the 5:00 pm IOP assessment. The primary efficacy outcome was change in diurnal IOP (the mean of IOP measurements) from baseline to week 8. Adverse effect (AE) data were recorded at each visit. A total of 229 patients were randomized (latanoprost, n = 112; dorzolamide/timolol, n = 117). Mean baseline diurnal IOP values were similar between the 2 groups. Mean (SD) diurnal IOP reductions at week 8 before the water-drinking test were 6.9 (3.0) mm Hg for the latanoprost group and 6.4 (3.2) mm Hg for the dorzolamide/timolol group. Mean IOP values were similar at all time points except at 5:00 pm, when levels were significantly lower in latanoprost-treated patients (P = 0.025). After the water-drinking test, the increase in IOP values was similar between groups at baseline but lower in latanoprost-treated patients at week 8 (adjusted difference, 1.08 mm Hg

  4. The FIND-CKD study--a randomized controlled trial of intravenous iron versus oral iron in non-dialysis chronic kidney disease patients: background and rationale.

    Science.gov (United States)

    Macdougall, Iain C; Bock, Andreas; Carrera, Fernando; Eckardt, Kai-Uwe; Gaillard, Carlo; Van Wyck, David; Roubert, Bernard; Cushway, Timothy; Roger, Simon D

    2014-04-01

    Rigorous data are sparse concerning the optimal route of administration and dosing strategy for iron therapy with or without concomitant erythropoiesis-stimulating agent (ESA) therapy for the management of iron deficiency anaemia in patients with non-dialysis dependent chronic kidney disease (ND-CKD). FIND-CKD was a 56-week, open-label, multicentre, prospective, randomized three-arm study (NCT00994318) of 626 patients with ND-CKD and iron deficiency anaemia randomized to (i) intravenous (IV) ferric carboxymaltose (FCM) at an initial dose of 1000 mg iron with subsequent dosing as necessary to target a serum ferritin level of 400-600 µg/L (ii) IV FCM at an initial dose of 200 mg with subsequent dosing as necessary to target serum ferritin 100-200 µg/L or (iii) oral ferrous sulphate 200 mg iron/day. The primary end point was time to initiation of other anaemia management (ESA therapy, iron therapy other than study drug or blood transfusion) or a haemoglobin (Hb) trigger (two consecutive Hb values FIND-CKD was the longest randomized trial of IV iron therapy to date. Its findings will address several unanswered questions regarding iron therapy to treat iron deficiency anaemia in patients with ND-CKD. It was also the first randomized trial to utilize both a high and low serum ferritin target range to adjust IV iron dosing, and the first not to employ Hb response as its primary end point.

  5. The sustained effect (12 months) of a single-dose vectored thermal pulsation procedure for meibomian gland dysfunction and evaporative dry eye.

    Science.gov (United States)

    Blackie, Caroline A; Coleman, Christy A; Holland, Edward J

    2016-01-01

    To evaluate the sustained effect (up to 1 year) of a single, 12-minute vectored thermal pulsation (VTP) treatment in improving meibomian gland function and dry eye symptoms in patients with meibomian gland dysfunction and evaporative dry eye. The prospective, multicenter, open-label clinical trial included 200 subjects (400 eyes) who were randomized to a single VTP treatment (treatment group) or twice-daily, 3-month, conventional warm compress and eyelid hygiene therapy (control group). Control group subjects received crossover VTP treatment at 3 months (crossover group). Effectiveness measures of meibomian gland secretion (MGS) and dry eye symptoms were evaluated at baseline and 1, 3, 6, 9, and 12 months. Subjects with inadequate symptom relief could receive additional meibomian gland dysfunction therapy after 3 (treatment group) and 6 months (crossover group). At 3 months, the treatment group had greater mean improvement in MGS (Pdry eye symptoms (P=0.0068), compared to controls. At 12 months, 86% of the treatment group had received only one VTP treatment, and sustained a mean improvement in MGS from 6.4±3.7 (baseline) to 17.3±9.1 (Pdry eye symptoms from 44.1±20.4 to 21.6±21.3 (Pdry eye symptoms from 49.1±21.0 to 24.0±23.2 (Pdry eye symptoms, over 12 months. A single VTP treatment provides significantly greater mean improvement in meibomian gland function and dry eye symptoms as compared to a conventional, twice-daily, 3-month regimen. Early VTP intervention for meibomian gland dysfunction is associated with improved treatment outcomes.

  6. Effects of formulation on the bioavailability of lutein and zeaxanthin: a randomized, double-blind, cross-over, comparative, single-dose study in healthy subjects.

    Science.gov (United States)

    Evans, Malkanthi; Beck, Mareike; Elliott, James; Etheve, Stephane; Roberts, Richard; Schalch, Wolfgang

    2013-06-01

    Lutein and zeaxanthin are macular pigments with a protective function in the retina. These xanthophylls must be obtained from the diet or added to foods or supplements via easy-to-use, stable formulations. The technique employed to produce these formulations may affect the bioavailability of the xanthophylls. Forty-eight healthy volunteers were randomized into this double-blind, cross-over study investigating the plasma kinetics of lutein provided as two different beadlet formulations. Subjects (n = 48) received a single dose of 20 mg of lutein as either a starch-matrix ("SMB", FloraGLO® Lutein 5 %) or as a cross-linked alginate-matrix beadlet ("AMB", Lyc-O-Lutein 20 %) formulation. Plasma concentrations of lutein and zeaxanthin were measured at 0, 1, 3, 6, 9, 12, 14, 24, 26, 28, 32, 36, 48, 72, 168, and 672 h. The mean plasma AUC(0-72h), AUC(0-672h), and C(max) for total lutein and zeaxanthin and their all-E-isomers were significantly increased (p < 0.001) from pre-dose concentrations in response to SMB and AMB. There was no difference in lutein T max between the two test articles. However, by 14 h post-dose, total plasma lutein increased by 7 % with AMB and by 126 % with SMB. Total lutein AUC(0-72h) and AUC(0-672h) were 1.8-fold and 1.3-fold higher, respectively, for SMB compared to AMB. Both formulations were well tolerated by subjects in this study. These findings confirm that the bioavailability of lutein and zeaxanthin critically depends on the formulation used and document a superiority of the starch-based over the alginate-based product in this study.

  7. Safety and tolerability of aripiprazole for irritability in pediatric patients with autistic disorder: a 52-week, open-label, multicenter study.

    Science.gov (United States)

    Marcus, Ronald N; Owen, Randall; Manos, George; Mankoski, Raymond; Kamen, Lisa; McQuade, Robert D; Carson, William H; Findling, Robert L

    2011-09-01

    Evaluate the long-term safety and tolerability of aripiprazole in the treatment of irritability in pediatric subjects (6-17 years) with autistic disorder. A 52-week, open-label, flexibly dosed (2-15 mg/d) study of the safety and tolerability of aripiprazole in outpatients with a DSM-IV-TR diagnosis of autistic disorder who either had completed 1 of 2 antecedent, 8-week randomized trials or were enrolled de novo (ie, not treated in the randomized trials). Safety and tolerability measures included incidences of adverse events, extrapyramidal symptoms, weight, metabolic measures, vital signs, and other clinical assessments. Subjects were enrolled between September 2006 and June 2009. Three hundred thirty subjects entered the treatment phase: 86 de novo, 174 prior aripiprazole, and 70 prior placebo. A total of 199 (60.3%) subjects completed 52 weeks of treatment. Adverse events were experienced by 286/330 subjects (86.7%). Common adverse events included weight increase, vomiting, nasopharyngitis, increased appetite, pyrexia, upper respiratory tract infection, and insomnia. Discontinuations due to adverse events occurred in 35/330 randomized subjects (10.6%)-most commonly aggression and weight increase. One patient discontinued from the study due to a laboratory-related adverse event (moderately increased alanine transaminase and aspartate transaminase). Nine subjects experienced serious adverse events-most frequently aggression. Extrapyramidal symptoms-related adverse events occurred in 48/330 subjects (14.5%)-most commonly tremor (3.0%), psychomotor hyperactivity (2.7%), akathisia (2.4%), and dyskinesia (not tardive, 2.4%). At > 9 months' aripiprazole exposure (n = 220), mean change in body weight z score was 0.33 and body mass index z score was 0.31. The percentages of subjects with clinically significant fasting metabolic abnormalities at > 9 months were 2% for glucose, 5% for total cholesterol, 7% for low-density lipoprotein cholesterol, 30% for high

  8. Rationale, Design, and Baseline Characteristics of the Utopia Trial for Preventing Diabetic Atherosclerosis Using an SGLT2 Inhibitor: A Prospective, Randomized, Open-Label, Parallel-Group Comparative Study.

    Science.gov (United States)

    Katakami, Naoto; Mita, Tomoya; Yoshii, Hidenori; Shiraiwa, Toshihiko; Yasuda, Tetsuyuki; Okada, Yosuke; Umayahara, Yutaka; Kaneto, Hideaki; Osonoi, Takeshi; Yamamoto, Tsunehiko; Kuribayashi, Nobuichi; Maeda, Kazuhisa; Yokoyama, Hiroki; Kosugi, Keisuke; Ohtoshi, Kentaro; Hayashi, Isao; Sumitani, Satoru; Tsugawa, Mamiko; Ohashi, Makoto; Taki, Hideki; Nakamura, Tadashi; Kawashima, Satoshi; Sato, Yasunori; Watada, Hirotaka; Shimomura, Iichiro

    2017-10-01

    Sodium-glucose co-transporter-2 (SGLT2) inhibitors are anti-diabetic agents that improve glycemic control with a low risk of hypoglycemia and ameliorate a variety of cardiovascular risk factors. The aim of the ongoing study described herein is to investigate the preventive effects of tofogliflozin, a potent and selective SGLT2 inhibitor, on the progression of atherosclerosis in subjects with type 2 diabetes (T2DM) using carotid intima-media thickness (IMT), an established marker of cardiovascular disease (CVD), as a marker. The Study of Using Tofogliflozin for Possible better Intervention against Atherosclerosis for type 2 diabetes patients (UTOPIA) trial is a prospective, randomized, open-label, blinded-endpoint, multicenter, and parallel-group comparative study. The aim was to recruit a total of 340 subjects with T2DM but no history of apparent CVD at 24 clinical sites and randomly allocate these to a tofogliflozin treatment group or a conventional treatment group using drugs other than SGLT2 inhibitors. As primary outcomes, changes in mean and maximum IMT of the common carotid artery during a 104-week treatment period will be measured by carotid echography. Secondary outcomes include changes in glycemic control, parameters related to β-cell function and diabetic nephropathy, the occurrence of CVD and adverse events, and biochemical measurements reflecting vascular function. This is the first study to address the effects of SGLT2 inhibitors on the progression of carotid IMT in subjects with T2DM without a history of CVD. The results will be available in the very near future, and these findings are expected to provide clinical data that will be helpful in the prevention of diabetic atherosclerosis and subsequent CVD. Kowa Co., Ltd. UMIN000017607.

  9. A 1-year study to compare the hemostatic effects of oral contraceptive containing 20 microg of ethinylestradiol and 100 microg of levonorgestrel with 30 microg of ethinylestradiol and 100 microg of levonorgestrel

    DEFF Research Database (Denmark)

    Jespersen, Jørgen; Endrikat, Jan; Düsterberg, Bernd

    2005-01-01

    OBJECTIVES: To comparatively evaluate the impact of a balanced one-third dose-reduced oral contraceptive on hemostatic variables. METHODS: In an open-label, randomized study, a dose-reduced oral contraceptive containing 20 microg of ethinylestradiol (EE) and 100 microg of levonorgestrel (LNG...

  10. Impact of one-dose package dispensing with patient counseling on medication adherence in geriatrics suffering from chronic disorders

    Directory of Open Access Journals (Sweden)

    Narayana Goruntla

    2018-01-01

    Full Text Available Introduction: Medication nonadherence in elderly patients could result in a waste of medical expenses in a long-time span as well as deterioration of the patient's medical condition. Aim: The aim of this study is to evaluate the impact of one-dose package dispensing with patient counseling on medication adherence among elderly patients suffering from chronic disorders. Settings and Design: This is prospective, open-labeled, randomized trial carried out at dispensing pharmacy of the secondary care referral hospital, located in resource-limited settings of Anantapur District, Andhra Pradesh, India. Subjects and Methods: A total of 330 (aged ≥60 years patients were randomly assigned to one of three study groups: Group A (n = 110, no change in dosing and packing; Group B (n = 110, one-dose package dispensing; Group C (n = 110, One-dose package dispensing with patient counseling. Medication adherence levels were measured using a pill count and visual analog scale (VAS method at baseline and follow-up (after 1 month. Statistical Analysis: Descriptive statistics were used to represent the sociodemographic, clinical, and medication adherence profile of study participants. One-way ANOVA test is used to assess significant differences between three groups with a P 60 years who are on multiple medications can benefit from one-dose package dispensing and appropriate counseling. This will improve medication adherence hence better outcomes.

  11. An open-label trial of aripiprazole in the treatment of aggression in male adolescents diagnosed with conduct disorder.

    Science.gov (United States)

    Kuperman, Samuel; Calarge, Chadi; Kolar, Anne; Holman, Timothy; Barnett, Mitchell; Perry, Paul

    2011-11-01

    The adverse effect profiles of typical and atypical antipsychotics are problematic because of their extrapyramidal and endocrine adverse effects, respectively. Ten adolescent male patients diagnosed with conduct disorder received aripiprazole in doses of ≤20 mg/d in an open-label, intent-to-treat design to establish and characterize the efficacy of the drug in reducing aggressive behavior. Based on clinician and parent observations, aripiprazole was effective in reducing aggressive behavior in adolescent boys. The change in clinician-observed aggression ratings appears to have been driven by a decrease in physical aggression, whereas the change in parent-observed aggression ratings appears to have been driven by a decrease in verbal aggression and aggression against objects and animals. Aripiprazole was an effective and relatively well-tolerated treatment for overall aggression in adolescent males with conduct disorder, in the view of both clinicians and parents. Depending on the observer, aripiprazole improved aggression categorized as physical aggression, verbal aggression, and aggression against objects and animals.

  12. Open-Access Single Balloon Enteroscopy: A Tertiary Care Experience.

    Science.gov (United States)

    Holman, Nathan; Wallace, Kristin; Moore, J Matthew; Brock, Andrew S

    2015-12-01

    To compare single balloon enteroscopy (SBE) between patients seen in consultation by a member of our gastroenterology team with those performed as open-access cases. Retrospective study of all patients who underwent SBE at a single tertiary care center from April 2008 to January 2012. Open- and closed-access procedures were compared in terms of diagnostic and therapeutic yield, adverse events, and procedural success. A total of 125 SBEs were performed on 125 patients. The mean age was 63.1 (53% men) years. In all, 43 procedures were performed open access and 82 after face-to-face consultation. Indications included anemia/gastrointestinal bleeding (110), abdominal pain (8), and other (7). Diagnostic yield for open- and closed-access procedures was 53% and 60%, respectively (P = 0.501) and therapeutic yield was 37% and 52%, respectively (P = 0.11). Overall technical success was 91% with no difference between the groups (P = 0.27). There were no major adverse events in either group. SBE can be performed as an open-access procedure without compromise to safety or diagnostic yield.

  13. Labeling of mesenchymal stem cells for MRI with single-cell sensitivity

    Directory of Open Access Journals (Sweden)

    Ariza de Schellenberger A

    2016-04-01

    Full Text Available Angela Ariza de Schellenberger,1 Harald Kratz,1 Tracy D Farr,2,3 Norbert Löwa,4 Ralf Hauptmann,1 Susanne Wagner,1 Matthias Taupitz,1 Jörg Schnorr,1 Eyk A Schellenberger1 1Department of Radiology, 2Department of Experimental Neurology, Center for Stroke Research Berlin, Charité – Universitätsmedizin Berlin, Berlin, Germany; 3School of Life Sciences, University of Nottingham, Medical School, Nottingham, UK; 4Department of Biomagnetic Signals, Physikalisch-Technische Bundesanstalt Berlin, Berlin, Germany Abstract: Sensitive cell detection by magnetic resonance imaging (MRI is an important tool for the development of cell therapies. However, clinically approved contrast agents that allow single-cell detection are currently not available. Therefore, we compared very small iron oxide nanoparticles (VSOP and new multicore carboxymethyl dextran-coated iron oxide nanoparticles (multicore particles, MCP designed by our department for magnetic particle imaging (MPI with discontinued Resovist® regarding their suitability for detection of single mesenchymal stem cells (MSC by MRI. We achieved an average intracellular nanoparticle (NP load of >10 pg Fe per cell without the use of transfection agents. NP loading did not lead to significantly different results in proliferation, colony formation, and multilineage in vitro differentiation assays in comparison to controls. MRI allowed single-cell detection using VSOP, MCP, and Resovist® in conjunction with high-resolution T2*-weighted imaging at 7 T with postprocessing of phase images in agarose cell phantoms and in vivo after delivery of 2,000 NP-labeled MSC into mouse brains via the left carotid artery. With optimized labeling conditions, a detection rate of ~45% was achieved; however, the experiments were limited by nonhomogeneous NP loading of the MSC population. Attempts should be made to achieve better cell separation for homogeneous NP loading and to thus improve NP

  14. A randomized, controlled study of an educational intervention to improve recall of auxiliary medication labeling and adherence to antibiotics

    Directory of Open Access Journals (Sweden)

    Jade A Pham

    2013-06-01

    Full Text Available Purpose: To evaluate whether medication counseling with emphasis on auxiliary labels improves recall of auxiliary label information and adherence to medication schedules. Methods: A prospective, randomized study of an educational intervention in community pharmacies near Baltimore, Maryland. Fifty literate, English-speaking adults receiving one of the 18 commonly dispensed antibiotics were randomized to receive a counseling session or no counseling. Five to seven days after medication pickup, a structured phone interview was conducted to capture data on recall of auxiliary labels and adherence. Results: A total of 39 subjects completed the phone interview (78%. The rate of correct recall was high: 77% correct recall for all three labels. Among those with incorrect recall, 7 out of 9 subjects received no counseling (p = 0.11. The auxiliary labels incorrectly recalled were all related to dietary restrictions. Conclusion: The findings from this study suggest that medication counseling emphasizing auxiliary label information may lead to improved recall and adherence to antibiotics. Additional studies are required to confirm the preliminary findings and determine whether they correspond to improved adherence. Information most commonly misunderstood were related to dietary restrictions. Additional research focusing on counseling related to dietary restrictions is recommended.

  15. Effect of Tailored Dose-Dense Chemotherapy vs Standard 3-Weekly Adjuvant Chemotherapy on Recurrence-Free Survival Among Women With High-Risk Early Breast Cancer: A Randomized Clinical Trial.

    Science.gov (United States)

    Foukakis, Theodoros; von Minckwitz, Gunter; Bengtsson, Nils-Olof; Brandberg, Yvonne; Wallberg, Birgitta; Fornander, Tommy; Mlineritsch, Brigitte; Schmatloch, Sabine; Singer, Christian F; Steger, Günther; Egle, Daniel; Karlsson, Eva; Carlsson, Lena; Loibl, Sibylle; Untch, Michael; Hellström, Mats; Johansson, Hemming; Anderson, Harald; Malmström, Per; Gnant, Michael; Greil, Richard; Möbus, Volker; Bergh, Jonas

    2016-11-08

    Standard dosing of chemotherapy based on body surface area results in marked interpatient variation in pharmacokinetics, toxic effects, and efficacy. Whether tailored dosing can improve outcomes is unknown, as is the role of dose-dense adjuvant chemotherapy. To determine whether tailored dose-dense adjuvant chemotherapy improves the outcomes of early breast cancer compared with a standard 3-weekly chemotherapy schedule. A randomized, open-label, phase 3 trial of women aged 65 years and younger who had surgery for nonmetastatic node-positive or high-risk node-negative breast cancer at 86 sites in Sweden, Germany, and Austria between February 20, 2007, and September 14, 2011. Patients were randomized 1:1 either to 4 cycles of leukocyte nadir-based tailored and dose-dense adjuvant epirubicin and cyclophosphamide every 2 weeks followed by 4 cycles of tailored dose-dense docetaxel every 2 weeks, or to standard-interval chemotherapy with 3 cycles of fluorouracil and epirubicin-cyclophosphamide every 3 weeks followed by 3 cycles of docetaxel every 3 weeks. The primary end point was breast cancer recurrence-free survival (BCRFS). Secondary end points included 5-year event-free survival (EFS), distant disease-free survival (DDFS), overall survival (OS), and rates of grade 3 or 4 toxic effects. Among 2017 randomized patients (1006 in the tailored dose-dense group and 1011 in the control group; median [IQR] age, 51 [45-58] years; 80% with hormone receptor-positive tumors; 97% with node-positive disease), 2000 received study treatment (≥1 cycle of chemotherapy; 1001 in the tailored dose-dense group and 999 in the control group). After a median follow-up of 5.3 years (IQR, 4.5-6.1 years), 269 BCRFS events were reported, 118 in the tailored dose-dense group and 151 in the control group (HR, 0.79; 95% CI, 0.61-1.01; log-rank P = .06; 5-year BCRFS, 88.7% vs 85.0%). The tailored dose-dense group had significantly better EFS than the control group (HR, 0.79; 95% CI, 0

  16. Noninvasive imaging of protein metabolic labeling in single human cells using stable isotopes and Raman microscopy

    NARCIS (Netherlands)

    van Manen, H.J.; Lenferink, Aufrid T.M.; Otto, Cornelis

    2008-01-01

    We have combined nonresonant Raman microspectroscopy and spectral imaging with stable isotope labeling by amino acids in cell culture (SILAC) to selectively detect the incorporation of deuterium-labeled phenylalanine, tyrosine, and methionine into proteins in intact, single HeLa cells. The C−D

  17. Single point estimation of phenytoin dosing: a reappraisal.

    Science.gov (United States)

    Koup, J R; Gibaldi, M; Godolphin, W

    1981-11-01

    A previously proposed method for estimation of phenytoin dosing requirement using a single serum sample obtained 24 hours after intravenous loading dose (18 mg/Kg) has been re-evaluated. Using more realistic values for the volume of distribution of phenytoin (0.4 to 1.2 L/Kg), simulations indicate that the proposed method will fail to consistently predict dosage requirements. Additional simulations indicate that two samples obtained during the 24 hour interval following the iv loading dose could be used to more reliably predict phenytoin dose requirement. Because of the nonlinear relationship which exists between phenytoin dose administration rate (RO) and the mean steady state serum concentration (CSS), small errors in prediction of the required RO result in much larger errors in CSS.

  18. The pharmacokinetics of peginterferon lambda-1a following single dose administration to subjects with impaired renal function.

    Science.gov (United States)

    Hruska, Matthew W; Adamczyk, Robert; Colston, Elizabeth; Hesney, Michael; Stonier, Michele; Myler, Heather; Bertz, Richard

    2015-09-01

    This open label study was conducted to assess the effect of renal impairment (RI) on the pharmacokinetics (PK) of peginterferon lambda-1a (Lambda). Subjects (age 18-75 years, BMI 18-35 kg m(-2) ) were enrolled into one of five renal function groups: normal (n = 12), mild RI (n = 8), moderate RI (n = 8), severe RI (n = 7), end-stage renal disease (ESRD, n = 8) based on estimated glomerular filtration rate (eGFR) calculated using the Modification of Diet in Renal Disease (MDRD) equation. Subjects received a single dose of Lambda (180 µg) subcutaneously on day 1 followed by PK serum sample collections through day 29. Safety, tolerability and immunogenicity data were collected through day 43. PK parameters were estimated and summarized by group. Geometric mean ratios (GMR) and 90% confidence intervals (CIs) were calculated between normal and RI groups. With decreasing eGFR, Lambda exposure (Cmax , AUC) increased while apparent clearance (CL/F) and apparent volume of distribution (V/F) decreased. Relative to subjects with normal renal function (geometric mean AUC = 99.5 ng ml(-1) h), Lambda exposure estimates (AUC) were slightly increased in the mild RI group (geometric mean [90% CI]: 1.20 [0.82, 1.77]) and greater in the moderate (1.95 [1.35, 2.83]), severe RI (1.95 [1.30, 2.93]) and ESRD (1.88 [1.30, 2.73]) groups. Lambda was generally well tolerated. The results demonstrated that RI reduces the clearance of Lambda and suggests that dose modifications may not be required in patients with mild RI but may be required in patients with moderate to severe RI or ESRD. © 2015 The British Pharmacological Society.

  19. Renoprotection of Optimal Antiproteinuric Doses (ROAD) Study: a randomized controlled study of benazepril and losartan in chronic renal insufficiency.

    Science.gov (United States)

    Hou, Fan Fan; Xie, Di; Zhang, Xun; Chen, Ping Yan; Zhang, Wei Ru; Liang, Min; Guo, Zhi Jian; Jiang, Jian Ping

    2007-06-01

    The Renoprotection of Optimal Antiproteinuric Doses (ROAD) study was performed to determine whether titration of benazepril or losartan to optimal antiproteinuric doses would safely improve the renal outcome in chronic renal insufficiency. A total of 360 patients who did not have diabetes and had proteinuria and chronic renal insufficiency were randomly assigned to four groups. Patients received open-label treatment with a conventional dosage of benazepril (10 mg/d), individual uptitration of benazepril (median 20 mg/d; range 10 to 40), a conventional dosage of losartan (50 mg/d), or individual uptitration of losartan (median 100 mg/d; range 50 to 200). Uptitration was performed to optimal antiproteinuric and tolerated dosages, and then these dosages were maintained. Median follow-up was 3.7 yr. The primary end point was time to the composite of a doubling of the serum creatinine, ESRD, or death. Secondary end points included changes in the level of proteinuria and the rate of progression of renal disease. Compared with the conventional dosages, optimal antiproteinuric dosages of benazepril and losartan that were achieved through uptitration were associated with a 51 and 53% reduction in the risk for the primary end point (P = 0.028 and 0.022, respectively). Optimal antiproteinuric dosages of benazepril and losartan, at comparable BP control, achieved a greater reduction in both proteinuria and the rate of decline in renal function compared with their conventional dosages. There was no significant difference for the overall incidence of major adverse events between groups that were given conventional and optimal dosages in both arms. It is concluded that uptitration of benazepril or losartan against proteinuria conferred further benefit on renal outcome in patients who did not have diabetes and had proteinuria and renal insufficiency.

  20. Pharmacokinetic Effects of Antidrug Antibodies Occurring in Healthy Subjects After a Single Dose of Intravenous Infliximab.

    Science.gov (United States)

    Ehrenpreis, Eli D

    2017-12-01

    Infliximab pharmacokinetic studies have been performed in patients receiving chronic infliximab therapy. In these patients, infliximab antidrug antibodies (ADAs) increase infliximab clearance and decrease serum levels and drug efficacy. This study analyzed the pharmacokinetic effect of infliximab ADAs in healthy subjects receiving a single dose of intravenous infliximab. Data were obtained from a single-blind, parallel-group, single-dose study of healthy subjects receiving 5 mg/kg of intravenous SB2 (infliximab biosimilar), EU-sourced Remicade (EU-IFX) or US-sourced Remicade (US-IFX). Serum infliximab was measured at 1, 2, 3, 6, 12, 24, 48, and 72 h and at 5, 7, 14, 21, 28, 42, 56, and 70 days after administration. ADAs were measured pre-dose and at 29 and 71 days. Data from the first ten subjects randomized to each treatment arm were utilized for this study. A two-compartment model of the serum infliximab vs. time curve was developed using nonlinear regression. At 10 weeks, 11 subjects (37%) developed ADAs. ADAs were detected in four subjects after SB2, one subject after EU-IFX, and six subjects after US-IFX infusion. Of these, neutralizing antibodies occurred in one subject after SB2, in no subjects after EU-IFX, and in three subjects after US-IFX infusion. Infliximab clearance was increased in subjects with ADAs vs. those without ADAs (12.89 ± 2.69 vs. 9.90 ± 1.74 ml/h; p ADAs (282.4 ± 56.4 vs. 343.3 ± 61.9 h; p ADAs are common in healthy subjects after a single intravenous dose of infliximab and result in faster infliximab clearance, shorter elimination time, and lower serum infliximab levels. These data confirm that ADAs are common with biologic therapy and significantly impact the efficacy of these drugs.

  1. Long-term safety and efficacy of etanercept in patients with psoriasis: an open-label study.

    NARCIS (Netherlands)

    Leonardi, C.; Strober, B.; Gottlieb, A.B.; Elewski, B.E.; Ortonne, J.P.; Kerkhof, P.C.M. van de; Chiou, C.F.; Dunn, M.; Jahreis, A.

    2010-01-01

    BACKGROUND: In two previous phase 3 studies, up to 60 weeks of etanercept therapy significantly improved the symptoms of psoriasis and was well tolerated. OBJECTIVE: To evaluate the long-term safety of etanercept in an open-label extension study for up to 72 weeks in patients with moderate-to-severe

  2. An information and communication technology-based centralized clinical trial to determine the efficacy and safety of insulin dose adjustment education based on a smartphone personal health record application: a randomized controlled trial.

    Science.gov (United States)

    Kim, Gyuri; Bae, Ji Cheol; Yi, Byoung Kee; Hur, Kyu Yeon; Chang, Dong Kyung; Lee, Moon-Kyu; Kim, Jae Hyeon; Jin, Sang-Man

    2017-07-18

    A Personal Health Record (PHR) is an online application that allows patients to access, manage, and share their health data. PHRs not only enhance shared decision making with healthcare providers, but also enable remote monitoring and at-home-collection of detailed data. The benefits of PHRs can be maximized in insulin dose adjustment for patients starting or intensifying insulin regimens, as frequent self-monitoring of glucose, self-adjustment of insulin dose, and precise at-home data collection during the visit-to-visit period are important for glycemic control. The aim of this study is to examine the efficacy and safety of insulin dose adjustment based on a smartphone PHR application in patients with diabetes mellitus (DM) and to confirm the validity and stability of an information and communication technology (ICT)-based centralized clinical trial monitoring system. This is a 24-week, open-label, randomized, multi-center trial. There are three follow-up measures: baseline, post-intervention at week 12, and at week 24. Subjects diagnosed with type 1 DM, type 2 DM, and/or post-transplant DM who initiate basal insulin or intensify their insulin regimen to a basal-bolus regimen are included. After education on insulin dose titration and prevention for hypoglycemia and a 1-week acclimation period, subjects are randomized in a 1:1 ratio to either an ICT-based intervention group or a conventional intervention group. Subjects in the conventional intervention group will save and send their health information to the server via a PHR application, whereas those in ICT-based intervention group will receive additional algorithm-based feedback messages. The health information includes level of blood glucose, insulin dose, details on hypoglycemia, food diary, and step count. The primary outcome will be the proportion of patients who reach an optimal insulin dose within 12 weeks of study enrollment, without severe hypoglycemia or unscheduled clinic visits. This clinical trial

  3. Single myelin fiber imaging in living rodents without labeling by deep optical coherence microscopy

    Science.gov (United States)

    Ben Arous, Juliette; Binding, Jonas; Léger, Jean-François; Casado, Mariano; Topilko, Piotr; Gigan, Sylvain; Claude Boccara, A.; Bourdieu, Laurent

    2011-11-01

    Myelin sheath disruption is responsible for multiple neuropathies in the central and peripheral nervous system. Myelin imaging has thus become an important diagnosis tool. However, in vivo imaging has been limited to either low-resolution techniques unable to resolve individual fibers or to low-penetration imaging of single fibers, which cannot provide quantitative information about large volumes of tissue, as required for diagnostic purposes. Here, we perform myelin imaging without labeling and at micron-scale resolution with >300-μm penetration depth on living rodents. This was achieved with a prototype [termed deep optical coherence microscopy (deep-OCM)] of a high-numerical aperture infrared full-field optical coherence microscope, which includes aberration correction for the compensation of refractive index mismatch and high-frame-rate interferometric measurements. We were able to measure the density of individual myelinated fibers in the rat cortex over a large volume of gray matter. In the peripheral nervous system, deep-OCM allows, after minor surgery, in situ imaging of single myelinated fibers over a large fraction of the sciatic nerve. This allows quantitative comparison of normal and Krox20 mutant mice, in which myelination in the peripheral nervous system is impaired. This opens promising perspectives for myelin chronic imaging in demyelinating diseases and for minimally invasive medical diagnosis.

  4. Single myelin fiber imaging in living rodents without labeling by deep optical coherence microscopy.

    Science.gov (United States)

    Ben Arous, Juliette; Binding, Jonas; Léger, Jean-François; Casado, Mariano; Topilko, Piotr; Gigan, Sylvain; Boccara, A Claude; Bourdieu, Laurent

    2011-11-01

    Myelin sheath disruption is responsible for multiple neuropathies in the central and peripheral nervous system. Myelin imaging has thus become an important diagnosis tool. However, in vivo imaging has been limited to either low-resolution techniques unable to resolve individual fibers or to low-penetration imaging of single fibers, which cannot provide quantitative information about large volumes of tissue, as required for diagnostic purposes. Here, we perform myelin imaging without labeling and at micron-scale resolution with >300-μm penetration depth on living rodents. This was achieved with a prototype [termed deep optical coherence microscopy (deep-OCM)] of a high-numerical aperture infrared full-field optical coherence microscope, which includes aberration correction for the compensation of refractive index mismatch and high-frame-rate interferometric measurements. We were able to measure the density of individual myelinated fibers in the rat cortex over a large volume of gray matter. In the peripheral nervous system, deep-OCM allows, after minor surgery, in situ imaging of single myelinated fibers over a large fraction of the sciatic nerve. This allows quantitative comparison of normal and Krox20 mutant mice, in which myelination in the peripheral nervous system is impaired. This opens promising perspectives for myelin chronic imaging in demyelinating diseases and for minimally invasive medical diagnosis.

  5. Magnetic resonance imaging of single co-labeled mesenchymal stromal cells after intracardial injection in mice

    International Nuclear Information System (INIS)

    Salamon, J.; Adam, G.; Peldschus, K.; Wicklein, D.; Schumacher, U.; Didie, M.; Lange, C.

    2014-01-01

    Purpose: The aim of this study was to establish co-labeling of mesenchymal stromal cells (MSC) for the detection of single MSC in-vivo by MRI and histological validation. Materials and Methods: Mouse MSC were co-labeled with fluorescent iron oxide micro-particles and carboxyfluorescein succinimidyl ester (CFSE). The cellular iron content was determined by atomic absorption spectrometry. Cell proliferation and expression of characteristic surface markers were determined by flow cytometry. The chondrogenic differentiation capacity was assessed. Different amounts of cells (n1 = 5000, n2 = 15 000, n3 = 50 000) were injected into the left heart ventricle of 12 mice. The animals underwent sequential MRI on a clinical 3.0T scanner (Intera, Philips Medical Systems, Best, The Netherlands). For histological validation cryosections were examined by fluorescent microscopy. Results: Magnetic and fluorescent labeling of MSC was established (mean cellular iron content 23.6 ± 3 pg). Flow cytometry showed similar cell proliferation and receptor expression of labeled and unlabeled MSC. Chondrogenic differentiation of labeled MSC was verified. After cell injection MRI revealed multiple signal voids in the brain and fewer signal voids in the kidneys. In the brain, an average of 4.6 ± 1.2 (n1), 9.0 ± 3.6 (n2) and 25.0 ± 1.0 (n3) signal voids were detected per MRI slice. An average of 8.7 ± 3.1 (n1), 22.0 ± 6.1 (n2) and 89.8 ± 6.5 (n3) labeled cells per corresponding stack of adjacent cryosections could be detected in the brain. Statistical correlation of the numbers of MRI signal voids in the brain and single MSC found by histology revealed a correlation coefficient of r = 0.91. Conclusion: The study demonstrates efficient magnetic and fluorescent co-labeling of MSC and their detection on a single cell level in mice by in-vivo MRI and histology. The described techniques may broaden the methods for in-vivo tracking of MSC. (orig.)

  6. Pharmacokinetics of sulfamethoxazole and trimethoprim in Pacific white shrimp, Litopenaeus vannamei, after oral administration of single-dose and multiple-dose.

    Science.gov (United States)

    Ma, Rongrong; Wang, Yuan; Zou, Xiong; Hu, Kun; Sun, Beibei; Fang, Wenhong; Fu, Guihong; Yang, Xianle

    2017-06-01

    The tissue distribution and depletion of sulfamethoxazole (SMZ) and trimethoprim (TMP) were studied in Pacific white shrimp, Litopenaeus vannamei, after single-dose and multiple-dose oral administration of SMZ-TMP (5:1) via medicated feed. In single-dose oral administration, shrimps were fed once at a dose of 100 mg/kg (drug weight/body weight). In multiple-dose oral administration, shrimps were fed three times a day for three consecutive days at a dose of 100mg/kg. The results showed the kinetic characteristic of SMZ was different from TMP in Pacific white shrimp. In the single-dose administration, the SMZ was widely distributed in the tissues, while TMP was highly concentrated in the hepatopancreas. The t 1/2z values of SMZ were larger and persist longer than TMP in Pacific white shrimp. In the multiple-dose administration, SMZ accumulated well in the tissues, and reached steady state level after successive administrations, while TMP did not. TMP concentration even appeared the downward trend with the increase of drug times. Compared with the single dose, the t 1/2z values of SMZ in hepatopancreas (8.22-11.33h) and muscle (6.53-10.92h) of Pacific white shrimps rose, but the haemolymph dropped (13.76-11.03) in the multiple-dose oral administration. Meanwhile, the corresponding values of TMP also rose in hepatopancreas (4.53-9.65h) and muscle (2.12-2.71h), and declined in haemolymph (7.38-5.25h) following single-dose and multiple-dose oral administration in Pacific white shrimps. In addition, it is worth mentioning that the ratios of SMZ and TMP were unusually larger than the general aim ratio. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. "Antifibrotic effect after low-dose imatinib mesylate treatment in patients with nephrogenic systemic fibrosis: An open-label non-randomized, uncontrolled clinical trial"

    DEFF Research Database (Denmark)

    Elmholdt, Tina Rask; Olesen, Anne Braae

    2011-01-01

    Background Nephrogenic systemic fibrosis is a disease affecting the connective tissue of the skin and internal organs in patients with renal failure. No effective treatments are available. Objectives To investigate if the tyrosine kinase inhibitor, imatinib mesylate was effective in patients...... Imatinib mesylate may be an effective drug in the treatment of skin fibrosis in moderate to severe NSF cases, even at reduced doses. We found a positive clinical effect on the skin, but no convincing improvement of the joint mobility. Only few patients could be recruited limiting the interpretation...

  8. Attention benefits after a single dose of metadoxine extended release in adults with predominantly inattentive ADHD.

    Science.gov (United States)

    Manor, Iris; Rubin, Jonathan; Daniely, Yaron; Adler, Lenard A

    2014-09-01

    To assess the first-dose effectiveness and tolerability of metadoxine extended release (MDX) in adults with predominantly inattentive attention-deficit/hyperactivity disorder (ADHD-PI). In this double-blind, placebo-controlled, crossover study, adults with ADHD-PI were randomized 1:1:1 to receive a single dose of MDX 1400 mg, MDX 700 mg, and placebo (ClinicalTrials.gov identifier: NCT01685281). The primary efficacy end point was the mean change in the Test of Variables of Attention (TOVA) ADHD score from baseline to 3 to 5 hours after drug administration. Secondary assessments included TOVA subscores, TOVA response rates (defined as an increase of 0.8 points in the TOVA ADHD score), and the Cambridge Neuropsychological Automated Test Battery. Safety assessments included adverse events and vital signs. The intention-to-treat population included 36 patients (52.8% men; mean age, 32 years). The efficacy of MDX 1400 mg was demonstrated by a statistically significant difference in the mean (± SD) change in the TOVA ADHD score at baseline to 3 to 5 hours after drug administration compared with placebo (2.0 [4.2]; P = 0.009). The TOVA response time variability subscore was significantly different between MDX 1400 mg and placebo (mean difference, 7.9 [19.2] points; P = 0.022). Significantly more adults responded to single-dose MDX 1400 mg versus placebo (97.1% vs 71.4%, P = 0.006). There were no statistically significant differences between MDX 700 mg and placebo on any measures. Exploratory analyses of the Cambridge Neuropsychological Automated Test Battery did not yield significant findings. Fatigue and headache were the 2 most frequently reported adverse events. There were no clinically significant abnormalities in laboratory values, vital signs measurements, Columbia-Suicide Severity Rating Scale scores, or electrocardiographic parameters. Single-dose MDX 1400 mg significantly improved sustained and selective attention in adults with ADHD-PI as measured by the TOVA

  9. Civamide cream 0.075% in patients with osteoarthritis of the knee: a 12-week randomized controlled clinical trial with a longterm extension.

    Science.gov (United States)

    Schnitzer, Thomas J; Pelletier, Jean-Pierre; Haselwood, Doug M; Ellison, William T; Ervin, John E; Gordon, Richard D; Lisse, Jeffrey R; Archambault, W Tad; Sampson, Allan R; Fezatte, Heidi B; Phillips, Scott B; Bernstein, Joel E

    2012-03-01

    To evaluate the safety and efficacy of civamide cream 0.075% for the treatment of osteoarthritis (OA) of the knee. We conducted a 12-week, multicenter, randomized, double-blind study with a 52-week open-label extension. Patients with OA of the knee received either civamide cream 0.075% or a lower dose of civamide cream, 0.01%, as the control. The 3 co-primary endpoints in the double-blind study were the time-weighted average (TWA) of change from baseline to Day 84 in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale, the WOMAC physical function subscale, and the Subject Global Evaluation (SGE). In the 52-week open-label extension study, the Osteoarthritis Pain Score and SGE were assessed. A total of 695 patients were randomized to receive civamide cream 0.075% (n = 351) or civamide cream 0.01% (control; n = 344) in the double-blind study. Significance in favor of civamide cream 0.075% was achieved for the TWA for all 3 co-primary efficacy variables: WOMAC pain (p = 0.009), WOMAC physical function (p < 0.001), and SGE (p = 0.008); and at Day 84 for these 3 variables (p = 0.013, p < 0.001, and p = 0.049, respectively). These analyses accounted for significant baseline-by-treatment interactions. In the 52-week open-label extension, efficacy was maintained. Civamide cream 0.075% was well tolerated throughout the studies. These studies demonstrate the efficacy of civamide cream for up to 1 year of continuous use. Civamide cream, with its lack of systemic absorption, does not have the potential for serious systemic toxicity, in contrast to several other OA treatments.

  10. The efficacy of preventive parasternal single injection of bupivacaine on intubation time, blood gas parameters, narcotic requirement, and pain relief after open heart surgery: A randomized clinical trial study

    Directory of Open Access Journals (Sweden)

    Mahmoud Saeidi

    2011-01-01

    Full Text Available Background: Postsurgical pain usually results in some complications in the patients. This study has tried to investigate the effects of parasternal single injection of bupivacaine on postoperative pulmonary and pain consequences in patients after open heart surgery. Methods: : In a prospective double blind clinical study, 100 consenting patients undergoing elective open heart surgery were randomized into two groups. In case group, bupivacaine was injected at both sides of sternum, immediately before sternal closure. In the control group, no intervention was performed. Then, the patients were investigated regarding intubation period, length of ICU stay, arterial blood gas (ABG parameters, morphine requirement, and their severity of postoperative pain using a visual analogue scale (VAS device. Results: No differences were found between the two groups regarding to age, sex, pump time, operation time, and body mass index and preoperative cardiac ejection fraction. Mean intubation length in case group was much shorter than that in control group. Mean PaO 2 in case group was lower in different checking times in postoperative period. The patients in the case group needed less morphine compared to those in the control group during the 24-hour observation period in the ICU. Finally, mean VAS scores of pain in case group were significantly lower than those in control group at 6, 12, and 24 hours postoperatively. Conclusions: Patients′ pain relief by parasternal single injection of bupivacaine in early postoperative period can facilitate earlier ventilator weaning and tracheal extubation after open heart surgery as well as achieving lower pain scores and narcotic requirements.

  11. Comparative randomized open-label trial on efficacy and safety of Persen® and Persen® Night herbal extracts in patients with short-term insomnia

    Directory of Open Access Journals (Sweden)

    A. P. Rachin

    2016-01-01

    Full Text Available Herbal sedatives serve an alternative to antipsychotics and hypnotics aimed to alleviate symptoms of anxious disorders and insomnia. Valeriana officinalis L., Mentha piperita L. and Melissa officinalis are most widely used in neurology as sedatives of herbal origin. We present the results of a randomized open-label trial on efficiency and safety of Persen® and Persen® Night containing extracts of the above mentioned plants in patients with short-term insomnia. The study consisted of 60 subjects of 18–65 y.o. (mean 42.4 ± 6.9 y.o. with short-term insomnia due to adjustment disorder or mixed anxiety-depressive disorders: 30 of them got Persen® 2 tablets a day and 30 – Persen® Night, 1 capsule 30–60 min before sleep during 4 weeks. The majority (76.5 % of patients referred the onset of insomnia with psychosocial traumatic stressor. Persen® Night’s main action was found on superficial sleep, number of night awakenings, sleep onset rate. At the end of the therapy with this substance 39.7 % of patients fell asleep in 10–15 min, and 92.2 % – in 30 min, accordingly, while for Persen® at 17.4 and 80.3 % accordingly (р < 0.05. In the meantime Persen® decreased the bad sleep perception at awakening and day somnolence, mostly attributed to the mood improvement and decrease of anxiety. Levels of efficacy and safety for both substances were significant, allowing to regard them as potential phytotherapeutic agent in the treatment of insomnia and mixed anxiety-depressive disorders.

  12. A combined phase I and II open label study on the effects of a seaweed extract nutrient complex on osteoarthritis

    Directory of Open Access Journals (Sweden)

    Stephen P Myers

    2010-02-01

    Full Text Available Stephen P Myers1,2, Joan O’Connor1,2, J Helen Fitton3, Lyndon Brooks4, Margaret Rolfe4, Paul Connellan5, Hans Wohlmuth2,5,6, Phil A Cheras1,2, Carol Morris51NatMed-Research, 2Centre for Health and Wellbeing, 4Graduate Research College, 5Centre for Phytochemistry and Pharmacology, 6Medicinal Plant Herbarium, Southern Cross University, Lismore, NSW, Australia; 3Marinova Pty Ltd, Hobart, Tasmania, AustraliaBackground: Isolated fucoidans from brown marine algae have been shown to have a range of anti-inflammatory effects.Purpose: This present study tested a Maritech® extract formulation, containing a blend of extracts from three different species of brown algae, plus nutrients in an open label combined phase I and II pilot scale study to determine both acute safety and efficacy in osteoarthritis of the knee. Patients and methods: Participants (n = 12, five females [mean age, 62 ± 11.06 years] and seven males [mean age, 57.14 ± 9.20 years] with a confirmed diagnosis of osteoarthritis of the knee were randomized to either 100 mg (n = 5 or 1000 mg (n = 7 of a Maritech® extract formulation per day. The formulation contained Maritech® seaweed extract containing Fucus vesiculosis (85% w/w, Macrocystis pyrifera (10% w/w and Laminaria japonica (5% w/w plus vitamin B6, zinc and manganese. Primary outcome was the average comprehensive arthritis test (COAT score which is comprised of four sub-scales: pain, stiffness, difficulty with physical activity and overall symptom severity measured weekly. Safety measures included full blood count, serum lipids, liver function tests, urea, creatinine and electrolytes determined at baseline and week 12. All adverse events were recorded.Results: Eleven participants completed 12 weeks and one completed 10 weeks of the study. Using a multilevel linear model, the average COAT score was reduced by 18% for the 100 mg treatment and 52% for the 1000 mg dose at the end of the study. There was a clear dose response effect

  13. Efficacy of various single-dose regimens of ceftriaxone in ...

    African Journals Online (AJOL)

    The therapeutic efficacy of single intramuscular doses of ceftriaxone (Rocephin; Roche) (62,S, 125 and 250 mg), administered without probenecid, was evaluated in 167 adult males with uncomplicated acute gonococcal urethritis. Cure rates of 100% were achieved at 62,5 mg and 250 mg. In the 125 mg dose group, ...

  14. 2-Year Efficacy, Immunogenicity, and Safety of Vigoo Enterovirus 71 Vaccine in Healthy Chinese Children: A Randomized Open-Label Study.

    Science.gov (United States)

    Wei, Mingwei; Meng, Fanyue; Wang, Shiyuan; Li, Jingxin; Zhang, Yuntao; Mao, Qunying; Hu, Yuemei; Liu, Pei; Shi, Nianmin; Tao, Hong; Chu, Kai; Wang, Yuxiao; Liang, Zhenglun; Li, Xiuling; Zhu, Fengcai

    2017-01-01

     This study evaluated the 2-year efficacy, immunogenicity, and safety of the Vigoo enterovirus 71 (EV71) vaccine.  In an initial phase 3 study, we randomly assigned healthy infants and children aged 6-35 months (ratio, 1:1) to receive 2 doses of either EV71 vaccine (5120 participants) or placebo (5125 participants) at days 0 and 28, and followed them for 12 months after vaccination. In this extended follow-up study, we continued to evaluate the efficacy, immunogenicity, and safety of the EV71 vaccine for up to 2 years.  Overall efficacy was 94.84% (95% confidence interval [CI], 83.53%-98.38%) during the 2-year follow-up period (P vaccine efficacy during the second year was 100.00% (95% CI, 84.15%-100.00%) against EV71-associated hand-foot-and-mouth disease (HFMD; P vaccine-related serious adverse events were recorded.  Two doses of Vigoo EV71 vaccine could provide sustained protection against EV71-associated HFMD in healthy Chinese children.  NCT01508247. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  15. SINGLE-DOSE VERSUS 3-DAY PROPHYLAXIS WITH CIPROFLOXACIN IN TRANSURETHRAL SURGERY - A CLINICAL-TRIAL

    NARCIS (Netherlands)

    BIJL, W; JANKNEGT, RA

    1993-01-01

    in 235 patients who underwent transurethral surgery, perioperative oral ciprofloxacin prophylaxis was given as a single dose 500 mg versus a 3-day regimen. Out of 180 evaluable patients, 84 received a single dose and 96 received a 3-day course. In the single dose prophylaxis group there were 5

  16. Averaging in SU(2) open quantum random walk

    International Nuclear Information System (INIS)

    Ampadu Clement

    2014-01-01

    We study the average position and the symmetry of the distribution in the SU(2) open quantum random walk (OQRW). We show that the average position in the central limit theorem (CLT) is non-uniform compared with the average position in the non-CLT. The symmetry of distribution is shown to be even in the CLT

  17. Averaging in SU(2) open quantum random walk

    Science.gov (United States)

    Clement, Ampadu

    2014-03-01

    We study the average position and the symmetry of the distribution in the SU(2) open quantum random walk (OQRW). We show that the average position in the central limit theorem (CLT) is non-uniform compared with the average position in the non-CLT. The symmetry of distribution is shown to be even in the CLT.

  18. C2 Nerve Field Stimulation for the Treatment of Fibromyalgia: A Prospective, Double-blind, Randomized, Controlled Cross-over Study.

    Science.gov (United States)

    Plazier, Mark; Ost, Jan; Stassijns, Gaëtane; De Ridder, Dirk; Vanneste, Sven

    2015-01-01

    Fibromyalgia is a condition characterized by widespread chronic pain. Due to the high prevalence and high costs, it has a substantial burden on society. Treatment results are diverse and only help a small subset of patients. C2 nerve field stimulation, aka occipital nerve stimulation, is helpful and a minimally invasive treatment for primary headache syndromes. Small C2 pilot studies seem to be beneficial in fibromyalgia. Forty patients were implanted with a subcutaneous electrode in the C2 dermatoma as part of a prospective, double-blind, randomized, controlled cross-over study followed by an open label follow up period of 6 months. The patients underwent 2 week periods of different doses of stimulation consisting of minimal (.1 mA), subthreshold, and suprathreshold (for paresthesias) in a randomized order. Twenty seven patients received a permanent implant and 25 completed the 6 month open label follow up period. During the 6 week trial phase of the study, patients had an overall decrease of 36% on the fibromyalgia impact questionnaire (FIQ), a decrease of 33% fibromyalgia pain and improvement of 42% on the impact on daily life activities and quality. These results imply an overall improvement in the disease burden, maintained at 6 months follow up, as well as an improvement in life quality of 50%. Seventy six percent of patients were satisfied or very satisfied with their treatment. There seems to be a dose-response curve, with increasing amplitudes leading to better clinical outcomes. Subcutaneous C2 nerve field stimulation seems to offer a safe and effective treatment option for selected medically intractable patients with fibromyalgia. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Wide brick tunnel randomization - an unequal allocation procedure that limits the imbalance in treatment totals.

    Science.gov (United States)

    Kuznetsova, Olga M; Tymofyeyev, Yevgen

    2014-04-30

    In open-label studies, partial predictability of permuted block randomization provides potential for selection bias. To lessen the selection bias in two-arm studies with equal allocation, a number of allocation procedures that limit the imbalance in treatment totals at a pre-specified level but do not require the exact balance at the ends of the blocks were developed. In studies with unequal allocation, however, the task of designing a randomization procedure that sets a pre-specified limit on imbalance in group totals is not resolved. Existing allocation procedures either do not preserve the allocation ratio at every allocation or do not include all allocation sequences that comply with the pre-specified imbalance threshold. Kuznetsova and Tymofyeyev described the brick tunnel randomization for studies with unequal allocation that preserves the allocation ratio at every step and, in the two-arm case, includes all sequences that satisfy the smallest possible imbalance threshold. This article introduces wide brick tunnel randomization for studies with unequal allocation that allows all allocation sequences with imbalance not exceeding any pre-specified threshold while preserving the allocation ratio at every step. In open-label studies, allowing a larger imbalance in treatment totals lowers selection bias because of the predictability of treatment assignments. The applications of the technique in two-arm and multi-arm open-label studies with unequal allocation are described. Copyright © 2013 John Wiley & Sons, Ltd.

  20. Isavuconazole absorption following oral administration in healthy subjects is comparable to intravenous dosing, and is not affected by food, or drugs that alter stomach pH.

    Science.gov (United States)

    Schmitt-Hoffmann, Anne; Desai, Amit; Kowalski, Donna; Pearlman, Helene; Yamazaki, Takao; Townsend, Robert

    2016-08-01

    Two openlabel, single-dose, randomized crossover studies and one open-label, multiple-dose, parallel group study in healthy volunteers were conducted with the prodrug, isavuconazonium sulfate, to determine absolute bioavailability of the active triazole, isavuconazole (EudraCT 2007-004949-15; n = 14), and the effect of food (EudraCT 2007- 004940-63; n = 26), and pH (NCT02128893; n = 24) on the absorption of isavuconazole. Isavuconazonium sulfate 744 mg designed to deliver 400 mg of the active triazole isavuconazole was administered in the absolute bioavailability (oral or intravenous (IV) (2-hour infusion)) and food-effect studies (oral). In the pH-effect study, isavuconazonium sulfate 372 mg designed to deliver 200 mg of isavuconazole was administered orally three times daily (t.i.d.) for 2 days, followed by a single daily oral dose for 3 days, in the presence of steady state esomeprazole dosed orally at 40 mg/day. Isavuconazole was well tolerated in each study. Bioavailability: Geometric least squares mean ratios (GLSMR; oral/IV) for isavuconazole AUC∞, and Cmax were 98% (90% confidence interval (CI): 94, 101) and 78% (90% CI: 72, 85), respectively. Food-effect: GLSMR (fed/fasted) for AUC∞ and Cmax of isavuconazole in plasma were 110% (90% CI: 102, 118) and 92% (90% CI: 86, 98), respectively. Median tmax was 5 hours with food and 3 hours under fasted conditions. pH-effect: GLSMR for isavuconazole AUCtau and Cmax were 108% (90% CI: 89, 130) and 105% (90% CI: 89, 124), respectively. Orally administered isavuconazonium sulfate effectively delivers isavuconazole, as evidenced by the fact that oral isavuconazole is bioequivalent to the IV formulation. Dose adjustments are not required when switching between oral and IV formulations, regardless of food or drugs that increase gastric pH.