WorldWideScience

Sample records for randomized open-label controlled

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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:

  9. 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.

  10. 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

  11. 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.

  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. 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.

  14. Atomoxetine Open-Label Trial in ADHD

    Directory of Open Access Journals (Sweden)

    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.

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. Single-center open-label randomized study of anemia management improvement in ESRD patients with secondary hyperparathyroidism

    Directory of Open Access Journals (Sweden)

    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.

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. The treatment of disc herniation-induced sciatica with infliximab - Results of a randomized, controlled, 3-month follow-up study

    NARCIS (Netherlands)

    Korhonen, T; Karppinen, J; Paimela, L; Malmivaara, A; Lindgren, KA; Jarvinen, S; Niinimaki, J; Veeger, N; Seitsalo, S; Hurri, H

    2005-01-01

    Study Design. A randomized controlled trial. Objectives. To evaluate the efficacy of infliximab, a monoclonal antibody against tumor necrosis factor (TNF)-alpha in a randomized controlled setting. Summary of Background Data. Recently, we obtained encouraging results in an open-label study of

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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....

  16. 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 

  17. 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.

  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. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. Open-closed-loop iterative learning control for a class of nonlinear systems with random data dropouts

    Science.gov (United States)

    Cheng, X. Y.; Wang, H. B.; Jia, Y. L.; Dong, YH

    2018-05-01

    In this paper, an open-closed-loop iterative learning control (ILC) algorithm is constructed for a class of nonlinear systems subjecting to random data dropouts. The ILC algorithm is implemented by a networked control system (NCS), where only the off-line data is transmitted by network while the real-time data is delivered in the point-to-point way. Thus, there are two controllers rather than one in the control system, which makes better use of the saved and current information and thereby improves the performance achieved by open-loop control alone. During the transfer of off-line data between the nonlinear plant and the remote controller data dropout occurs randomly and the data dropout rate is modeled as a binary Bernoulli random variable. Both measurement and control data dropouts are taken into consideration simultaneously. The convergence criterion is derived based on rigorous analysis. Finally, the simulation results verify the effectiveness of the proposed method.

  5. Randomized controlled trial of ethyl-eicosapentaenoic acid in Huntington disease: the TREND-HD study.

    Science.gov (United States)

    2008-12-01

    To determine whether ethyl-eicosapentaenoic acid (ethyl-EPA), an omega-3 fatty acid, improves the motor features of Huntington disease. Six-month multicenter, randomized, double-blind, placebo-controlled trial followed by a 6-month open-label phase without disclosing initial treatment assignments. Forty-one research sites in the United States and Canada. Three hundred sixteen adults with Huntington disease, enriched for a population with shorter trinucleotide (cytosine-adenine-guanine) repeat length expansions. Random assignment to placebo or ethyl-EPA, 1 g twice a day, followed by open-label treatment with ethyl-EPA. Six-month change in the Total Motor Score 4 component of the Unified Huntington's Disease Rating Scale analyzed for all research participants and those with shorter cytosine-adenine-guanine repeat length expansions (<45). At 6 months, the Total Motor Score 4 point change for patients receiving ethyl-EPA did not differ from that for those receiving placebo. No differences were found in measures of function, cognition, or global impression. Before public disclosure of the 6-month placebo-controlled results, 192 individuals completed the open-label phase. The Total Motor Score 4 change did not worsen for those who received active treatment for 12 continuous months compared with those who received active treatment for only 6 months (2.0-point worsening; P=.02). Ethyl-EPA was not beneficial in patients with Huntington disease during 6 months of placebo-controlled evaluation. Clinical Trial Registry clinicaltrials.gov Identifier: NCT00146211.

  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. 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.

  8. 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.

  9. 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

  10. Matching of treatment-resistant heroin-dependent patients to medical prescription of heroin or oral methadone treatment: results from two randomized controlled trials

    NARCIS (Netherlands)

    Blanken, Peter; Hendriks, Vincent M.; Koeter, Maarten W. J.; van Ree, Jan M.; van den Brink, Wim

    2005-01-01

    AIMS: To investigate which baseline patient characteristics of treatment-resistant heroin addicts differentially predicted treatment response to medical heroin prescription compared to standard methadone maintenance treatment. DESIGN: Two open-label randomized controlled trials; pooled data.

  11. 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

  12. 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 .

  13. 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.

  14. Effect of Oral Beta-Hydroxy-Beta-Methylbutyrate (HMB Supplementation on Physical Performance in Healthy Old Women Over 65 Years: An Open Label Randomized Controlled Trial.

    Directory of Open Access Journals (Sweden)

    Linda Berton

    Full Text Available Although older people are particularly liable to sarcopenia, limited research is available on beta-hydroxy-beta-methylbutyrate (HMB supplementation in this population, particularly in healthy subjects. In this parallel-group, randomized, controlled, open-label trial, we aimed to evaluate whether an oral supplement containing 1.5 g of calcium HMB for 8 weeks could improve physical performance and muscle strength parameters in a group of community-dwelling healthy older women. Eighty healthy women attending a twice-weekly mild fitness program were divided into two equal groups of 40, and 32 of the treated women and 33 control completed the study. We considered a change in the Short Physical Performance Battery (SPPB score as the primary outcome and changes in the peak torque (PT isometric and isokinetic strength of the lower limbs, 6-minute walking test (6MWT, handgrip strength and endurance as secondary outcomes. Body composition was assessed with dual-energy X-ray absorptiometry (DXA and peripheral quantitative computerized tomography (pQCT. The mean difference between the two groups on pre-post change were finally calculated (delta for each outcome. After 8 weeks, there were no significant differences between the groups’ SPPB, handgrip strength or DXA parameters. The group treated with HMB scored significantly better than the control group for PT isokinetic flexion (delta = 1.56±1.56 Nm; p = 0.03 and extension (delta = 3.32±2.61 Nm; p = 0.03, PT isometric strength (delta = 9.74±3.90 Nm; p = 0.02, 6MWT (delta = 7.67±8.29 m; p = 0.04, handgrip endurance (delta = 21.41±16.28 s; p = 0.02, and muscle density assessed with pQCT. No serious adverse effects were reported in either group. In conclusion, a nutritional supplement containing 1.5 g of calcium HMB for 8 weeks in healthy elderly women had no significant effects on SPPB, but did significantly improve several muscle strength and physical performance parameters.ClinicalTrials.gov NCT

  15. Effect of Oral Beta-Hydroxy-Beta-Methylbutyrate (HMB) Supplementation on Physical Performance in Healthy Old Women Over 65 Years: An Open Label Randomized Controlled Trial.

    Science.gov (United States)

    Berton, Linda; Bano, Giulia; Carraro, Sara; Veronese, Nicola; Pizzato, Simona; Bolzetta, Francesco; De Rui, Marina; Valmorbida, Elena; De Ronch, Irene; Perissinotto, Egle; Coin, Alessandra; Manzato, Enzo; Sergi, Giuseppe

    2015-01-01

    Although older people are particularly liable to sarcopenia, limited research is available on beta-hydroxy-beta-methylbutyrate (HMB) supplementation in this population, particularly in healthy subjects. In this parallel-group, randomized, controlled, open-label trial, we aimed to evaluate whether an oral supplement containing 1.5 g of calcium HMB for 8 weeks could improve physical performance and muscle strength parameters in a group of community-dwelling healthy older women. Eighty healthy women attending a twice-weekly mild fitness program were divided into two equal groups of 40, and 32 of the treated women and 33 control completed the study. We considered a change in the Short Physical Performance Battery (SPPB) score as the primary outcome and changes in the peak torque (PT) isometric and isokinetic strength of the lower limbs, 6-minute walking test (6MWT), handgrip strength and endurance as secondary outcomes. Body composition was assessed with dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computerized tomography (pQCT). The mean difference between the two groups on pre-post change were finally calculated (delta) for each outcome. After 8 weeks, there were no significant differences between the groups’ SPPB, handgrip strength or DXA parameters. The group treated with HMB scored significantly better than the control group for PT isokinetic flexion (delta = 1.56±1.56 Nm; p = 0.03) and extension (delta = 3.32±2.61 Nm; p = 0.03), PT isometric strength (delta = 9.74±3.90 Nm; p = 0.02), 6MWT (delta = 7.67±8.29 m; p = 0.04), handgrip endurance (delta = 21.41±16.28 s; p = 0.02), and muscle density assessed with pQCT. No serious adverse effects were reported in either group. In conclusion, a nutritional supplement containing 1.5 g of calcium HMB for 8 weeks in healthy elderly women had no significant effects on SPPB, but did significantly improve several muscle strength and physical performance parameters. ClinicalTrials.gov NCT02118181.

  16. 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

  17. Comparison of efficacy and safety of topiramate with gabapentin in migraine prophylaxis: randomized open label control trial

    International Nuclear Information System (INIS)

    Zain, S.; Khan, M.; Alam, R.; Zafar, I.; Ahmed, S.

    2013-01-01

    Objective: To compare the efficacy and safety of topiramate with gabapentin in the prophylaxis of migraine patients. Methods: A 12-week randomised open label control trial was conducted at the Department of Pharmacology and Therapeutics, Basic Medical Sciences Institute, Jinnah Postgraduate Medical Centre (JPMC), Karachi from January to March 2011 involving 80 outpatients who had a history of migraine. The sample was divided into two equal groups. Primary efficacy measure was changed into mean monthly migraine frequency. Secondary efficacy measure included reduction in severity and average duration of an attack. Chi square test and paired t-test were used to analyse the data through SPSS 15. Result: Reduction in mean monthly migraine frequency (10.67+-4.25 to 1.82+-2.02) in the topiramate group was significantly greater compared with (11.97+-4.452 to 2.73+-2.59) that in the gabapentin group (p<0.001). Reduction in severity from 6.60+-2.122 to 1.03+-0.92 in the topiramate group was also significantly greater compared with 6.93+-1.90 to 1.18+-1.01 in the gabapentin group (p<0.001). Reduction in the average duration of attacks from 25.77+-22.32 hours to 1.0 1.06 hours in the topiramate group was significantly greater compared with 22.20+-20.72 to 1.08+-1.40 hours in the gabapentin group (p<0.001). Weight loss and numbness were common adverse effects in the topiramate group. Dizziness, weight gain and somnolence were reported in the gabapentin group. Conclusion: Gabapentin appeared well tolerated in 30(75%) patients compared to topiramate in 23(57.5%) patients. Both drugs were equally effective in migraine prophylaxis. (author)

  18. Determinants of Dropout and Nonadherence in a Dementia Prevention Randomized Controlled Trial: The Prevention of Dementia by Intensive Vascular Care Trial

    NARCIS (Netherlands)

    Beishuizen, Cathrien R. L.; Coley, Nicola; Moll van Charante, Eric P.; van Gool, Willem A.; Richard, Edo; Andrieu, Sandrine

    2017-01-01

    To explore and compare sociodemographic, clinical, and neuropsychiatric determinants of dropout and nonadherence in older people participating in an open-label cluster-randomized controlled trial-the Prevention of Dementia by Intensive Vascular care (preDIVA) trial-over 6 years. Secondary analysis.

  19. Determinants of Dropout and Nonadherence in a Dementia Prevention Randomized Controlled Trial: The Prevention of Dementia by Intensive Vascular Care Trial

    NARCIS (Netherlands)

    Beishuizen, C.R.; Coley, N.; Charante, E.P.M. van; Gool, W.A. van; Richard, E.; Andrieu, S.

    2017-01-01

    OBJECTIVES: To explore and compare sociodemographic, clinical, and neuropsychiatric determinants of dropout and nonadherence in older people participating in an open-label cluster-randomized controlled trial-the Prevention of Dementia by Intensive Vascular care (preDIVA) trial-over 6 years. DESIGN:

  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. 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.

  2. Traffic-light labels and financial incentives to reduce sugar-sweetened beverage purchases by low-income Latino families: a randomized controlled trial.

    Science.gov (United States)

    Franckle, Rebecca L; Levy, Douglas E; Macias-Navarro, Lorena; Rimm, Eric B; Thorndike, Anne N

    2018-06-01

    The objective of the present study was to test the effectiveness of financial incentives and traffic-light labels to reduce purchases of sugar-sweetened beverages in a community supermarket. In this randomized controlled trial, after a 2-month baseline period (February-March 2014), in-store traffic-light labels were posted to indicate healthy (green), less healthy (yellow) or unhealthy (red) beverages. During the subsequent five months (April-August 2014), participants in the intervention arm were eligible to earn a $US 25 in-store gift card each month they refrained from purchasing red-labelled beverages. Urban supermarket in Chelsea, MA, USA, a low-income Latino community. Participants were customers of this supermarket who had at least one child living at home. A total of 148 customers (n 77 in the intervention group and n 71 in the control group) were included in the final analyses. Outcomes were monthly in-store purchases tracked using a store loyalty card and self-reported consumption of red-labelled beverages. Compared with control participants, the proportion of intervention participants who purchased any red-labelled beverages decreased by 9 % more per month (P=0·002). More intervention than control participants reduced their consumption of red-labelled beverages (-23 % v. -2 % for consuming ≥1 red beverage/week, P=0·01). Overall, financial incentives paired with in-store traffic-light labels modestly reduced purchase and consumption of sugar-sweetened beverages by customers of a community supermarket.

  3. Maintenance N-acetyl cysteine treatment for bipolar disorder: A double-blind randomized placebo controlled trial

    Directory of Open Access Journals (Sweden)

    Berk Michael

    2012-08-01

    Full Text Available Abstract Background N-acetyl cysteine (NAC is a glutathione precursor that has been shown to have antidepressant efficacy in a placebo-controlled trial. The current study aimed to investigate the maintenance effects of NAC following eight weeks of open-label treatment for bipolar disorder. Method The efficacy of a double blind randomized placebo controlled trial of 2 g/day NAC as adjunct maintenance treatment for bipolar disorder was examined. Participants (n = 149 had a Montgomery Asberg Depression Rating Score of ≥12 at trial entry and, after eight weeks of open-label NAC treatment, were randomized to adjunctive NAC or placebo, in addition to treatment as usual. Participants (primarily outpatients were recruited through public and private services and through newspaper advertisements. Time to intervention for a mood episode was the primary endpoint of the study, and changes in mood symptoms, functionality and quality of life measures were secondary outcomes. Results There was a substantial decrease in symptoms during the eight-week open-label NAC treatment phase. During the subsequent double-blind phase, there was minimal further change in outcome measures with scores remaining low. Consequently, from this low plateau, between-group differences did not emerge on recurrence, clinical functioning or quality of life measures. Conclusions There were no significant between-group differences in recurrence or symptomatic outcomes during the maintenance phase of the trial; however, these findings may be confounded by limitations. Trial Registration The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12607000074493.

  4. 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.

  5. Randomized, Double-Blind, Placebo-Controlled Trial of Asenapine Maintenance Therapy in Adults With an Acute Manic or Mixed Episode Associated With Bipolar I Disorder.

    Science.gov (United States)

    Szegedi, Armin; Durgam, Suresh; Mackle, Mary; Yu, Sung Yun; Wu, Xiao; Mathews, Maju; Landbloom, Ronald P

    2018-01-01

    The authors determined the efficacy and safety of asenapine in preventing recurrence of any mood episode in adults with bipolar I disorder. Adults with an acute manic or mixed episode per DSM-IV-TR criteria were enrolled in this randomized, placebo-controlled trial consisting of an initial 12- to 16-week open-label period and a 26-week double-blind randomized withdrawal period. The target asenapine dosage was 10 mg b.i.d. in the open-label period but could be titrated down to 5 mg b.i.d. After completing the open-label period, subjects meeting stabilization/stable-responder criteria were randomized to asenapine or placebo treatment in the double-blind period. The primary efficacy endpoint was time to recurrence of any mood event during the double-blind period. Kaplan-Meier estimation was performed, and 95% confidence intervals were determined. Safety was assessed throughout. A total of 549 subjects entered the open-label period, of whom 253 enrolled in the double-blind randomized withdrawal period (127 in the placebo group; 126 in the asenapine group). Time to recurrence of any mood episode was statistically significantly longer for asenapine- than placebo-treated subjects. In post hoc analyses, significant differences in favor of asenapine over placebo were seen in time to recurrence of manic and depressive episodes. The most common treatment-emergent adverse events were somnolence (10.0%), akathisia (7.7%), and sedation (7.7%) in the open-label period and mania (11.9% of the placebo group compared with 4.0% of the asenapine group) and bipolar I disorder (6.3% compared with 1.6%) in the double-blind period. Long-term treatment with asenapine was more effective than placebo in preventing recurrence of mood events in adults with bipolar I disorder and was generally well-tolerated.

  6. 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

  7. 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.

  8. 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.

  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. Sodium lactate improves renal microvascular thrombosis compared to sodium bicarbonate and 0.9% NaCl in a porcine model of endotoxic shock: an experimental randomized open label controlled study.

    Science.gov (United States)

    Duburcq, Thibault; Durand, Arthur; Tournoys, Antoine; Gnemmi, Viviane; Gmyr, Valery; Pattou, François; Jourdain, Mercedes; Tamion, Fabienne; Besnier, Emmanuel; Préau, Sebastien; Parmentier-Decrucq, Erika; Mathieu, Daniel; Poissy, Julien; Favory, Raphaël

    2018-02-14

    Sodium lactate seemed to improve fluid balance and avoid fluid overload. The objective of this study was to determine if these beneficial effects can be at least partly explained by an improvement in disseminated intravascular coagulation (DIC)-associated renal microvascular thrombosis. Ancillary work of an interventional randomized open label controlled experimental study. Fifteen female "Large White" pigs (2 months old) were challenged with intravenous infusion of E. coli endotoxin. Three groups of five animals were randomly assigned to receive different fluids: a treatment group received sodium lactate 11.2% (SL group); an isotonic control group received 0.9% NaCl (NC group); a hypertonic control group, with the same amount of osmoles and sodium than SL group, received sodium bicarbonate 8.4% (SB group). Glomerular filtration rate (GFR) markers, coagulation and inflammation parameters were measured over a 5-h period. Immediately after euthanasia, kidneys were withdrawn for histological study. Statistical analysis was performed with nonparametric tests and the Dunn correction for multiple comparisons. A p < 0.05 was considered significant. The direct immunofluorescence study revealed that the percentage of capillary sections thrombosed in glomerulus were significantly lesser in SL group [5 (0-28) %] compared to NC [64 (43-79) %, p = 0.01] and SB [64 (43-79), p = 0.03] groups. Alterations in platelet count and fibrinogen level occurred earlier and were significantly more pronounced in both control groups compared to SL group (p < 0.05 at 210 and 300 min). The increase in thrombin-antithrombin complexes was significantly higher in NC [754 (367-945) μg/mL; p = 0.03] and SB [463 (249-592) μg/mL; p = 0.03] groups than in SL group [176 (37-265) μg/mL]. At the end of the experiment, creatinine clearance was significantly higher in SL group [55.46 (30.07-67.85) mL/min] compared to NC group [1.52 (0.17-27.67) mL/min, p = 0.03]. In this study, we

  11. Tinospora cordifolia stem supplementation in diabetic dyslipidemia: an open labelled randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Kuhu Roy

    2015-08-01

    Full Text Available Background: Medicinal plants are powerful health promoting nutritional agents. Among the vast library of medicinal plants Tinospora cordifolia (Willd. has been meagrely explored. It belongs to the family Menispermaceae and is a rich source of alkaloid and terpenes. It has hepatoprotective, antioxidant, immunostimulatory, hyperlipidemic, anticancer and antidiabetic properties. The stem contains berberine, palmatine, tembetarine, magnoflorine, tinosporin, tinocordifolin. The stem starch is highly nutritive and digestive. In modern medicine it is called the magical rejuvenating herb owing to its properties to cure many diseases. The stem contains higher alkaloid content than the leaves because of which it is approved for medicinal usage. With a host of phytochemical properties present in the stem, it may hold potential to manage dyslipidemia and dysglycemia, which otherwise has been proven only in pre-clinical studies. Objective: To study the impact of tinospora cordifolia stem supplementation on the glycemic and lipemic profile of subjects with diabetic dyslipidemia. Methods: Type 2 diabetics with dyslipidemia on oral hypoglycemic agents were enrolled. Baseline data on medical history, family history of lifestyle diseases, duration of diabetes diagnosis, drug profile, anthropometric data, dietary data and physical activity data was obtained along with a fasting blood sample for estimating high sensitivity C reactive protein (hs-CRP, hepatic, renal, lipid profile and glycated hemoglobin. The participants were randomized into either of the two groups; intervention group (n=29 received 250mg of encapsulated mature stem of tinospora cordifolia pre meal twice a day along with prescribed dyslipidemic agent and control group (n=30 only on dyslipidemic agents for a period of 60 days. After 60 days all the parameters were re-assessed to analyse the impact of the intervention. Results: Majority of the subjects in both the arms were in the 50-60 years age

  12. 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.

  13. Transdermal granisetron versus palonosetron for prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy: a multicenter, randomized, open-label, cross-over, active-controlled, and phase IV study.

    Science.gov (United States)

    Seol, Young Mi; Kim, Hyo Jeong; Choi, Young Jin; Lee, Eun Mi; Kim, Yang Soo; Oh, Sung Yong; Koh, Su Jin; Baek, Jin Ho; Lee, Won Sik; Joo, Young Don; Lee, Hyun Gi; Yun, Eun Young; Chung, Joo Seop

    2016-02-01

    Palonosetron is the second-generation 5-hydroxytryptamine 3 receptor antagonist (5-HT3RA) that has shown better efficacy than the first-generation 5-HT3RA for prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic chemotherapy (MEC). Granisetron transdermal delivery system (GTDS), a novel transdermal formulation, was developed to deliver granisetron continuously over 7 days. This study compared the efficacy and tolerability of the GTDS to palonosetron for the control of CINV following MEC. A total of 196 patients were randomized to GP or PG group. In this multicenter, randomized, open-label, cross-over, active-controlled, Phase IV study, GP group was assigned to receive transdermal granisetron (one GTDS patch, 7 days) in the first chemotherapy cycle, palonosetron (iv 0.25 mg/day, 1 days) in the second chemotherapy cycle before receiving MEC, and PG group was assigned to receive palonosetron in the first cycle and GTDS in the second cycle. Primary endpoint was the percentage of chemotherapy cycles achieving complete response (CR; defined as no emetic episodes and no rescue medication use) during the acute phase (0-24 h in post-chemotherapy; non-inferiority comparison with palonosetron). Total 333 cycles (165 in GTDS and 168 in palonosetron) were included in the per protocol analysis. The GTDS cycles showed non-inferiority to palonosetron cycles during the acute phase: CR was achieved by 124 (75.2 %) patients in the GTDS cycles and 134 (79.8 %) patients in the palonosetron cycles (treatment difference, -4.6 %; 95 % confidence interval, -13.6-4.4). There was no significant difference in CR rate during acute phase after the end of the first and second chemotherapy cycle between GP and PG group (p = 0.405, p = 0.074). Patients' satisfaction, assessed using Functional Living Index-Emesis (FLI-E), GTDS cycle were higher than those of palonosetron cycle in GP group (FLI-E score; median 1549.5 in GTDS cycle, median 1670

  14. 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.

  15. 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...

  16. Randomized controlled trial for assessment of Internet of Things system to guide intensive glucose control in diabetes outpatients : Nagoya Health Navigator Study protocol

    OpenAIRE

    Onoue, Takeshi; Goto, Motomitsu; Kobayashi, Tomoko; Tominaga, Takashi; Ando, Masahiko; Honda, Hiroyuki; Yoshida, Yasuko; Tosaki, Takahiro; Yokoi, Hisashi; Kato, Sawako; Maruyama, Shoichi; Arima, Hiroshi

    2017-01-01

    ABSTRACT The Internet of Things (IoT) allows collecting vast amounts of health-relevant data such as daily activity, body weight (BW), and blood pressure (BP) automatically. The use of IoT devices to monitor diabetic patients has been studied, but could not evaluate IoT-dependent effects because health data were not measured in control groups. This multicenter, open-label, randomized, parallel group study will compare the impact of intensive health guidance using IoT and conventional medical ...

  17. 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.

  18. 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.

  19. 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

  20. Yogurt supplemented with probiotics can protect the healthy elderly from respiratory infections: A randomized controlled open-label trial.

    Science.gov (United States)

    Pu, Fangfang; Guo, Yue; Li, Ming; Zhu, Hong; Wang, Shijie; Shen, Xi; He, Miao; Huang, Chengyu; He, Fang

    2017-01-01

    To evaluate whether yogurt supplemented with a probiotic strain could protect middle-aged and elderly people from acute upper respiratory tract infections (URTI) using a randomized, blank-controlled, parallel-group design. Two hundred and five volunteers aged ≥45 years were randomly divided into two groups. The subjects in the intervention group were orally administered 300 mL/d of yogurt supplemented with a probiotic strain, Lactobacillus paracasei N1115 (N1115), 3.6×10 7 CFU/mL for 12 weeks, while those in the control group retained their normal diet without any probiotic supplementation. The primary outcome was the incidence of URTI, and changes in serum protein, immunoglobulins, and the profiles of the T-lymphocyte subsets (total T-cells [CD3 + ], T-helper cells [CD4 + ], and T-cytotoxic-suppressor cells [CD8 + ]) during the intervention were the secondary outcomes. Compared to the control group, the number of persons diagnosed with an acute URTI and the number of URTI events significantly decreased in the intervention group ( P =0.038, P =0.030, respectively). The risk of URTI in the intervention group was evaluated as 55% of that in the control group (relative risk =0.55, 95% CI: 0.307-0.969). The change in the percentage of CD3 + cells in the intervention group was significantly higher than in the control group ( P =0.038). However, no significant differences were observed in the total protein, albumin, globulin, and prealbumin levels in both groups ( P >0.05). The study suggested that yogurt with selected probiotic strains such as N1115 may reduce the risk of acute upper tract infections in the elderly. The enhancement of the T-cell-mediated natural immune defense might be one of the important underlying mechanisms for probiotics to express their anti-infective effects.

  1. 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.

  2. 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.

  3. Variable versus conventional lung protective mechanical ventilation during open abdominal surgery: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Spieth, Peter M; Güldner, Andreas; Uhlig, Christopher; Bluth, Thomas; Kiss, Thomas; Schultz, Marcus J; Pelosi, Paolo; Koch, Thea; Gama de Abreu, Marcelo

    2014-05-02

    General anesthesia usually requires mechanical ventilation, which is traditionally accomplished with constant tidal volumes in volume- or pressure-controlled modes. Experimental studies suggest that the use of variable tidal volumes (variable ventilation) recruits lung tissue, improves pulmonary function and reduces systemic inflammatory response. However, it is currently not known whether patients undergoing open abdominal surgery might benefit from intraoperative variable ventilation. The PROtective VARiable ventilation trial ('PROVAR') is a single center, randomized controlled trial enrolling 50 patients who are planning for open abdominal surgery expected to last longer than 3 hours. PROVAR compares conventional (non-variable) lung protective ventilation (CV) with variable lung protective ventilation (VV) regarding pulmonary function and inflammatory response. The primary endpoint of the study is the forced vital capacity on the first postoperative day. Secondary endpoints include further lung function tests, plasma cytokine levels, spatial distribution of ventilation assessed by means of electrical impedance tomography and postoperative pulmonary complications. We hypothesize that VV improves lung function and reduces systemic inflammatory response compared to CV in patients receiving mechanical ventilation during general anesthesia for open abdominal surgery longer than 3 hours. PROVAR is the first randomized controlled trial aiming at intra- and postoperative effects of VV on lung function. This study may help to define the role of VV during general anesthesia requiring mechanical ventilation. Clinicaltrials.gov NCT01683578 (registered on September 3 3012).

  4. Minimally invasive versus open distal pancreatectomy (LEOPARD): study protocol for a randomized controlled trial.

    Science.gov (United States)

    de Rooij, Thijs; van Hilst, Jony; Vogel, Jantien A; van Santvoort, Hjalmar C; de Boer, Marieke T; Boerma, Djamila; van den Boezem, Peter B; Bonsing, Bert A; Bosscha, Koop; Coene, Peter-Paul; Daams, Freek; van Dam, Ronald M; Dijkgraaf, Marcel G; van Eijck, Casper H; Festen, Sebastiaan; Gerhards, Michael F; Groot Koerkamp, Bas; Hagendoorn, Jeroen; van der Harst, Erwin; de Hingh, Ignace H; Dejong, Cees H; Kazemier, Geert; Klaase, Joost; de Kleine, Ruben H; van Laarhoven, Cornelis J; Lips, Daan J; Luyer, Misha D; Molenaar, I Quintus; Nieuwenhuijs, Vincent B; Patijn, Gijs A; Roos, Daphne; Scheepers, Joris J; van der Schelling, George P; Steenvoorde, Pascal; Swijnenburg, Rutger-Jan; Wijsman, Jan H; Abu Hilal, Moh'd; Busch, Olivier R; Besselink, Marc G

    2017-04-08

    Observational cohort studies have suggested that minimally invasive distal pancreatectomy (MIDP) is associated with better short-term outcomes compared with open distal pancreatectomy (ODP), such as less intraoperative blood loss, lower morbidity, shorter length of hospital stay, and reduced total costs. Confounding by indication has probably influenced these findings, given that case-matched studies failed to confirm the superiority of MIDP. This accentuates the need for multicenter randomized controlled trials, which are currently lacking. We hypothesize that time to functional recovery is shorter after MIDP compared with ODP even in an enhanced recovery setting. LEOPARD is a randomized controlled, parallel-group, patient-blinded, multicenter, superiority trial in all 17 centers of the Dutch Pancreatic Cancer Group. A total of 102 patients with symptomatic benign, premalignant or malignant disease will be randomly allocated to undergo MIDP or ODP in an enhanced recovery setting. The primary outcome is time (days) to functional recovery, defined as all of the following: independently mobile at the preoperative level, sufficient pain control with oral medication alone, ability to maintain sufficient (i.e. >50%) daily required caloric intake, no intravenous fluid administration and no signs of infection. Secondary outcomes are operative and postoperative outcomes, including clinically relevant complications, mortality, quality of life and costs. The LEOPARD trial is designed to investigate whether MIDP reduces the time to functional recovery compared with ODP in an enhanced recovery setting. Dutch Trial Register, NTR5188 . Registered on 9 April 2015.

  5. Topical Coconut Oil in Very Preterm Infants: An Open-Label Randomised Controlled Trial.

    Science.gov (United States)

    Strunk, Tobias; Pupala, Sameer; Hibbert, Julie; Doherty, Dorota; Patole, Sanjay

    2018-01-01

    The immature fragile skin of preterm infants represents an inadequate protective barrier. The emollient and anti-infective properties of coconut oil make it a potentially beneficial topical agent for this population. Our aim was to evaluate feasibility, safety, and the effects of topical coconut oil on skin condition in very preterm infants. An open-label randomised controlled trial in preterm infants coconut oil (5 mL/kg) twice daily for 21 days, starting within 24 h of birth. The neonatal skin condition was the primary outcome, and was assessed using the Neonatal Skin Condition Score (NSCS) on days 1, 7, 14, and 21. The number of coconut oil applications was recorded to assess clinical feasibility and all enrolled infants were monitored for adverse effects of topical coconut application, such as skin irritation. A total of 72 infants born coconut oil was feasible and without adverse effects. The NSCS was maintained in the coconut oil group throughout the intervention period, but deteriorated from a median (IQR) of 3 (3-4) on day 1 to 4 (4-4) on day 21 in the control group (p = 0.01). There were no differences in common neonatal outcomes, including sepsis, necrotising enterocolitis, retinopathy of prematurity, chronic lung disease, and mortality. Topical coconut oil maintained a better skin condition in very preterm infants without adverse effects. This simple, safe, and affordable intervention warrants further investigation. © 2017 S. Karger AG, Basel.

  6. A single dose, randomized, open-label, cross-over bioequivalence study of sildenafil citrate tablets in healthy Chinese volunteers
.

    Science.gov (United States)

    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.
.

  7. 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.

  8. Robotic Label Applicator: Design, Development and Visual Servoing Based Control

    Directory of Open Access Journals (Sweden)

    Lin Chyi-Yeu

    2016-01-01

    Full Text Available Use of robotic arms and computer vision in manufacture, and assembly process are getting more interest as flexible customization is becoming priority over mass production as frontier industry practice. In this paper an innovative label applicator as end of arm tooling (EOAT capable of dispensing and applying label stickers of various dimensions to a product is designed, fabricated and tested. The system incorporates a label dispenserapplicator and had eye-in-hand camera system, attached to 6-dof robot arm can autonomously apply a label sticker to the target position on a randomly placed product. Employing multiple advantages from different knowledge basis, mechanism design and vision based automatic control, offers this system distinctive efficiency as well as flexibility to change in manufacturing and assembly process with time and cost saving.

  9. Laparoscopic versus open repair for perforated peptic ulcer: A meta analysis of randomized controlled trials.

    Science.gov (United States)

    Tan, Shanjun; Wu, Guohao; Zhuang, Qiulin; Xi, Qiulei; Meng, Qingyang; Jiang, Yi; Han, Yusong; Yu, Chao; Yu, Zhen; Li, Ning

    2016-09-01

    The role of laparoscopic surgery in the repair for peptic ulcer disease is unclear. The present study aimed to compare the safety and efficacy of laparoscopic versus open repair for peptic ulcer disease. Randomized controlled trials (RCTs) comparing laparoscopic versus open repair for peptic ulcer disease were identified from MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and references of identified articles and relevant reviews. Primary outcomes were postoperative complications, mortality, and reoperation. Secondary outcomes were operative time, postoperative pain, postoperative hospital stay, nasogastric tube duration, and time to resume diet. Statistical analysis was carried out by Review Manage software. Five RCTs investigating a total of 549 patients, of whom, 279 received laparoscopic repair and 270 received open repair, were included in the final analysis. There were no significant differences between these two procedures in some primary outcomes including overal postoperative complication rate, mortality, and reoperation rate. Subcategory analysis of postoperative complications showed that laparoscopic repair had also similar rates of repair site leakage, intra-abdominal abscess, postoperative ileus, pneumonia, and urinary tract infection as open surgery, except of the lower surgical site infection rate (P peptic ulcer. The obvious advantages of laparoscopic surgery are the lower surgical site infection rate, shorter nasogastric tube duration and less postoperative pain. However, more higher quality studies should be undertaken to further assess the safety and efficacy of laparoscopic repair for peptic ulcer disease. Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

  10. Do authors report surgical expertise in open spine surgery related randomized controlled trials? A systematic review on quality of reporting

    NARCIS (Netherlands)

    van Oldenrijk, Jakob; van Berkel, Youri; Kerkhoffs, Gino M. M. J.; Bhandari, Mohit; Poolman, Rudolf W.

    2013-01-01

    A systematic review of published trials in orthopedic spine literature. To determine the quality of reporting in open spine surgery randomized controlled trials (RCTs) between 2005 and 2010 with special focus on the reporting of surgical skill or expertise. In technically demanding procedures such

  11. 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.

  12. 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

  13. 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.

  14. Ziprasidone Augmentation of Escitalopram for Major Depressive Disorder: Efficacy Results From a Randomized, Double-Blind, Placebo-Controlled Study.

    Science.gov (United States)

    Papakostas, George I; Fava, Maurizio; Baer, Lee; Swee, Michaela B; Jaeger, Adrienne; Bobo, William V; Shelton, Richard C

    2015-12-01

    The authors sought to test the efficacy of adjunctive ziprasidone in adults with nonpsychotic unipolar major depression experiencing persistent symptoms after 8 weeks of open-label treatment with escitalopram. This was an 8-week, randomized, double-blind, parallel-group, placebo-controlled trial conducted at three academic medical centers. Participants were 139 outpatients with persistent symptoms of major depression after an 8-week open-label trial of escitalopram (phase 1), randomly assigned in a 1:1 ratio to receive adjunctive ziprasidone (escitalopram plus ziprasidone, N=71) or adjunctive placebo (escitalopram plus placebo, N=68), with 8 weekly follow-up assessments. The primary outcome measure was clinical response, defined as a reduction of at least 50% in score on the 17-item Hamilton Depression Rating Scale (HAM-D). The Hamilton Anxiety Rating scale (HAM-A) and Visual Analog Scale for Pain were defined a priori as key secondary outcome measures. Rates of clinical response (35.2% compared with 20.5%) and mean improvement in HAM-D total scores (-6.4 [SD=6.4] compared with -3.3 [SD=6.2]) were significantly greater for the escitalopram plus ziprasidone group. Several secondary measures of antidepressant efficacy also favored adjunctive ziprasidone. The escitalopram plus ziprasidone group also showed significantly greater improvement on HAM-A score but not on Visual Analog Scale for Pain score. Ten (14%) patients in the escitalopram plus ziprasidone group discontinued treatment because of intolerance, compared with none in the escitalopram plus placebo group. Ziprasidone as an adjunct to escitalopram demonstrated antidepressant efficacy in adult patients with major depressive disorder experiencing persistent symptoms after 8 weeks of open-label treatment with escitalopram.

  15. 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.

  16. Day-and-night glycaemic control with closed-loop insulin delivery versus conventional insulin pump therapy in free-living adults with well controlled type 1 diabetes: an open-label, randomised, crossover study.

    Science.gov (United States)

    Bally, Lia; Thabit, Hood; Kojzar, Harald; Mader, Julia K; Qerimi-Hyseni, Jehona; Hartnell, Sara; Tauschmann, Martin; Allen, Janet M; Wilinska, Malgorzata E; Pieber, Thomas R; Evans, Mark L; Hovorka, Roman

    2017-04-01

    Tight control of blood glucose concentration in people with type 1 diabetes predisposes to hypoglycaemia. We aimed to investigate whether day-and-night hybrid closed-loop insulin delivery can improve glucose control while alleviating the risk of hypoglycaemia in adults with HbA 1c below 7·5% (58 mmol/mol). In this open-label, randomised, crossover study, we recruited adults (aged ≥18 years) with type 1 diabetes and HbA 1c below 7·5% from Addenbrooke's Hospital (Cambridge, UK) and Medical University of Graz (Graz, Austria). After a 2-4 week run-in period, participants were randomly assigned (1:1), using web-based randomly permuted blocks of four, to receive insulin via the day-and-night hybrid closed-loop system or usual pump therapy for 4 weeks, followed by a 2-4 week washout period and then the other intervention for 4 weeks. Treatment interventions were unsupervised and done under free-living conditions. During the closed-loop period, a model-predictive control algorithm directed insulin delivery, and prandial insulin delivery was calculated with a standard bolus wizard. The primary outcome was the proportion of time when sensor glucose concentration was in target range (3·9-10·0 mmol/L) over the 4 week study period. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT02727231, and is completed. Between March 21 and June 24, 2016, we recruited 31 participants, of whom 29 were randomised. One participant withdrew during the first closed-loop period because of dissatisfaction with study devices and glucose control. The proportion of time when sensor glucose concentration was in target range was 10·5 percentage points higher (95% CI 7·6-13·4; pday-and-night hybrid closed-loop insulin delivery under unsupervised, free-living conditions for 4 weeks in adults with type 1 diabetes and HbA 1c below 7·5% is safe and well tolerated, improves glucose control, and reduces hypoglycaemia burden. Larger and longer studies

  17. 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

  18. 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.

  19. 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

  20. Financial incentives for improving adherence to maintenance treatment in patients with psychotic disorders (Money for Medication): a multicentre, open-label, randomised controlled trial.

    Science.gov (United States)

    Noordraven, Ernst L; Wierdsma, André I; Blanken, Peter; Bloemendaal, Anthony F T; Staring, Anton B P; Mulder, Cornelis L

    2017-03-01

    Provision of financial incentives is a promising intervention for improving adherence in patients taking antipsychotic medication. We aimed to assess the effectiveness of this intervention for improving adherence to antipsychotic depot medication in patients with psychotic disorders, irrespective of their previous compliance. We did this multicentre, open-label, randomised controlled trial at three mental health-care institutions in secondary psychiatric care services in the Netherlands. Eligible patients were aged 18-65 years, had been diagnosed with schizophrenia or another psychotic disorder, had been prescribed antipsychotic depot medication or had an indication to start using depot medication, and were participating in outpatient treatment. Patients were randomly assigned (1:1), via computer-generated randomisation with a block size of four, to receive 12 months of either treatment as usual plus a financial reward for each depot of medication received (€30 per month if fully compliant; intervention group) or treatment as usual alone (control group). Randomisation was stratified by treatment site and suspected prognostic factors: sex, comorbid substance-use disorder (absent vs present), and compliance with antipsychotic medication in the 4 months before baseline (taking antipsychotic medication. We did analysis by intention to treat. This trial is registered with the Nederlands Trial Register, number NTR2350. Between May 21, 2010, and Oct 15, 2014, we randomly assigned 169 patients to the intervention group (n=84) or the control group (n=85). Primary outcome data were available for 155 (92%) patients. At baseline, the mean MPR was 76·0% (SD 28·2%) in the intervention group versus 77·9% (28·5%) in the control group. At 12 months, the mean MPR was higher in the intervention group (94·3% [SD 11·3%]) than in the control group (80·3% [19·1%]), with an adjusted difference of 14·9% (95% CI 8·9-20·9%; pcontrol group (adjusted difference 6·5%, 95% CI 2·0

  1. Superiority of dutasteride over finasteride in hair regrowth and reversal of miniaturization in men with androgenetic alopecia: A randomized controlled open-label, evaluator-blinded study

    Directory of Open Access Journals (Sweden)

    Sujit J.S Shanshanwal

    2017-01-01

    Full Text Available Background: Finasteride and dutasteride are inhibitors of the enzyme 5-alpha-reductase which inhibits the conversion of testosterone to dihydrotestosterone. Dutasteride inhibits both type I and type II 5-alpha-reductase while finasteride inhibits only the type II enzyme. As both isoenzymes are present in hair follicles, it is likely that dutasteride is more effective than finasteride. Aims: To compare the efficacy, safety and tolerability of dutasteride and finasteride in men with androgenetic alopecia. Methods: Men with androgenetic alopecia between 18 and 40 years of age were randomized to receive 0.5 mg dutasteride or 1 mg finasteride daily for 24 weeks. The primary efficacy variables were hair counts (thick and thin in the target area from modified phototrichograms and global photography evaluation by blinded and non-blinded investigators. The secondary efficacy variable was subjective assessment using a preset questionnaire. Patients were assessed monthly for side effects. Results: Ninety men with androgenetic alopecia were recruited. The increase in total hair count per cm[2] representing new growth was significantly higher in dutasteride group (baseline- 223 hair; at 24 weeks- 246 hair compared to finasteride group (baseline- 227 hair; at 24 weeks- 231 hair. The decrease in thin hair count per cm[2] suggestive of reversal of miniaturization was significantly higher in dutasteride group (baseline- 65 hair; at 24 weeks- 57 hair compared to finasteride group (baseline- 67 hair; at 24 weeks- 66 hair. Both the groups showed a similar side effect profile with sexual dysfunction being the most common and reversible side effect. Limitations: Limitations include the short duration of the study (6 months, the small sample size and the fact that it was an open-label study. Conclusions: Dutasteride was shown to be more efficacious than finasteride and the side-effect profiles were comparable.

  2. School-based mindfulness intervention for stress reduction in adolescents: Design and methodology of an open-label, parallel group, randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Jeanette M. Johnstone

    2016-12-01

    Full Text Available Adolescents are in a high-risk period developmentally, in terms of susceptibility to stress. A mindfulness intervention represents a potentially useful strategy for developing cognitive and emotion regulation skills associated with successful stress coping. Mindfulness strategies have been used successfully for emotional coping in adults, but are not as well studied in youth. This article details a novel proposal for the design of an 8-week randomized study to evaluate a high school-based mindfulness curriculum delivered as part of a two semester health class. A wellness education intervention is proposed as an active control, along with a waitlist control condition. All students enrolled in a sophomore (10th grade health class at a private suburban high school will be invited to participate (n = 300. Pre-test assessments will be obtained by youth report, parent ratings, and on-site behavioral testing. The assessments will evaluate baseline stress, mood, emotional coping, controlled attention, and working memory. Participants, divided into 13 classrooms, will be randomized into one of three conditions, by classroom: A mindfulness intervention, an active control (wellness education, and a passive control (waitlist. Waitlisted participants will receive one of the interventions in the following term. Intervention groups will meet weekly for 8 weeks during regularly scheduled health classes. Immediate post-tests will be conducted, followed by a 60-day post-test. It is hypothesized that the mindfulness intervention will outperform the other conditions with regard to the adolescents' mood, attention and response to stress.

  3. 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.

  4. Chest closure without drainage after open patent ductus arteriosus ligation in Ugandan children: A non blinded randomized controlled trial.

    Science.gov (United States)

    Kebba, Naomi; Mwambu, Tom; Oketcho, Michael; Izudi, Jonathan; Obuku, Ekwaro A

    2016-09-29

    There is clinical equipoise regarding post-operative management of patients with patent ductus arteriosus (PDA) without insertion of a chest drain. This study evaluated post operative outcomes of chest closure with or without a drain following Patent Ductus Arteriosus ligation among childen at Uganda Heart Instritute (UHI). This was an open label randomized controlled trial of 62 children 12 years of age and below diagnosed with patent ductus arteriosus at Mulago National Teaching and Referral Hospital, Uganda. Participants were randomized in the ratio of 1:1 with surgical ligation of patent ductus arteriosus to either thoracotomy closure with a chest tube or without a chest tube. All participants received standard care and were monitored hourly for 24 hours then until hospital discharge. The combined primary endpoint consisted of significant pleural space accumulation of fluid or air, higher oxygen need or infection of the surgical site. Analysis was conducted by multivariable logistic regression analysis at 5 % significance level. We enrolled 62 participants, 46 (74 %) of whom were females. Their median age was 12 months (IQR: 8-36). Participants in the no-drain arm significantly had less post-operative complications compared to the drain arm (Unadjusted odds ratio [uOR]: 0.21, 95 % CI: 0.06-0.73, p = 0.015). This "protective effect" remained without statistical significance in the multivariable regression model (Adjusted odds ratio [aOR]: 0.07, 95 % CI: 0.00-2.50, p = 0.144). Children aged below 6 years with patent ductus arterious can safely and effectively have thoracotomy closure without using a drain in uncomplicated surgical ligation of the PDA. Chest drain was associated with post-operative complications. The trial was registered in the Pan African Clinical Trials registry on 1st/July/2012, retrospectively registered. Identifier number PACTR201207000395469 .

  5. Qigong and Fibromyalgia: Randomized Controlled Trials and Beyond

    Directory of Open Access Journals (Sweden)

    Jana Sawynok

    2014-01-01

    Full Text Available Introduction. Qigong is currently considered as meditative movement, mindful exercise, or complementary exercise and is being explored for relief of symptoms in fibromyalgia. Aim. This narrative review summarizes randomized controlled trials, as well as additional studies, of qigong published to the end of 2013 and discusses relevant methodological issues. Results. Controlled trials indicate regular qigong practice (daily, 6–8 weeks produces improvements in core domains for fibromyalgia (pain, sleep, impact, and physical and mental function that are maintained at 4–6 months compared to wait-list subjects or baselines. Comparisons with active controls show little difference, but compared to baseline there are significant and comparable effects in both groups. Open-label studies provide information that supports benefit but remain exploratory. An extension trial and case studies involving extended practice (daily, 6–12 months indicate marked benefits but are limited by the number of participants. Benefit appears to be related to amount of practice. Conclusions. There is considerable potential for qigong to be a useful complementary practice for the management of fibromyalgia. However, there are unique methodological challenges, and exploration of its clinical potential will need to focus on pragmatic issues and consider a spectrum of trial designs. Mechanistic considerations need to consider both system-wide and more specific effects.

  6. 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.

  7. 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

  8. 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.

  9. 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

  10. Multicenter, Randomized, Controlled Study Comparing Tafluprost/Timolol Fixed Combination with Latanoprost/Timolol Fixed Combination in Primary Open-Angle Glaucoma and Ocular Hypertension.

    Science.gov (United States)

    Suzuki, Katsuyoshi; Otsuka, Naomi; Hizaki, Hiroko; Hashimoto, Masayo; Kuwayama, Yasuaki

    2018-06-05

    This was the first exploratory randomized controlled study to compare the efficacy and safety of a preserved tafluprost/timolol fixed combination (TAF/TIM) with a preserved latanoprost/timolol fixed combination (LAT/TIM). This prospective, randomized, open-label study was conducted in Japanese patients with primary open-angle glaucoma, including normal-tension glaucoma or ocular hypertension. Following a 4-week LAT/TIM run-in period, eligible patients entered a 12-week treatment period, during which they received either LAT/TIM or TAF/TIM. The efficacy endpoint was the change in intraocular pressure (IOP) from baseline to week 12 and the safety endpoints included the changes from baseline to week 12 in superficial punctate keratopathy (SPK) score, tear breakup time (TBUT), and hyperemia score, as well as adverse events (AEs). At week 6, ocular symptoms were evaluated using a questionnaire. In total, 131 patients provided informed consent. Of these, 115 completed the run-in period and were assigned to receive TAF/TIM (n = 60) or LAT/TIM (n = 55). At week 12, there were no significant differences between the TAF/TIM and LAT/TIM groups in the change from baseline in trough IOP and IOP at 4-6 h after instillation. There were no significant differences between the two groups in the change from baseline to week 12 in SPK score, TBUT, and hyperemia score. However, only in the TAF/TIM group, the total SPK score and the inferior cornea SPK score were significantly lower at week 12 compared with baseline. Eye irritation and eye pain were significantly decreased in the TAF/TIM group compared with the LAT/TIM group. Two treatment-related AEs were reported in the TAF/TIM group (3.3%) and none in the LAT/TIM group, while no serious AEs were reported in either group. TAF/TIM is as effective as LAT/TIM in terms of IOP-reducing effect, with fewer ocular symptoms. TAF/TIM was associated with a significant improvement in SPK scores. UMIN Clinical Trials Registry Identifier

  11. Comparative study of amrutbhallataka and glucosamine sulphate in osteoarthritis: Six months open label randomized controlled clinical trial

    Directory of Open Access Journals (Sweden)

    Ashwinikumar Raut

    2013-01-01

    Full Text Available Background: AmrutBhallatak (ABFN02, a ′rasayana′ drug from Ayurveda is indicated in degenerative diseases and arthritis. Objective: To evaluate safety and efficacy of ABFN02 in osteoarthritis (OA and compare it with Glucosamine sulphate (GS Materials and Methods: This was a r andomized open comparative study. Ambulant OPD patients of OA knees (n = 112 were enrolled for 24 weeks. Tablets (750mg each of GS and ABFN02 were matched. Three groups of patients: (A GS, one tablet × twice/day × 24 weeks. (B ABFN02, incremental pulse dosage (one tablet x twice/day × two weeks, two tablets × twice/day × two weeks, three tablets × twice/day × two weeks, two such cycles of drug and non-drug phases alternately for six weeks each (C ABFN02 continuous dosage akin to GS. Pain visual analogue score (Pain-VAS and Western Ontario and Mc-Master University Osteoarthritis Index (WOMAC were the primary outcome measures. Secondary outcome measures were Health assessment questionnaire (HAQ, paracetamol consumption, 50 feet walking, physician and patient global assessment, knee stiffness, knee status, urinary CTX II, serum TNFa-SRI, SRII and MRI knee in randomly selected patients. Results: ABFNO2 and GS demonstrated, adherence to treatment 87.75% and 74.3%, reduction in Pain-VAS at rest 61.05% and 57.1%, reduction in pain-VAS on activity 57.4% and 59.8%, WOMAC score drop 62.8% and 59.1% respectively. Secondary outcome measures were comparable in all groups. Safety measures were also comparable. No serious adverse events reported. However, asymptomatic reversible rise in liver enzymes was noted in the ABFNO2 group. Conclusions: ABFN02 has significant activity in OA; the formulation needs further investigation.

  12. 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

  13. 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

  14. Unblinded randomized control trial on prophylactic antibiotic use in gustilo II open tibia fractures at Kenyatta National Hospital, Kenya.

    Science.gov (United States)

    Ondari, Joshua Nyaribari; Masika, Moses Muia; Ombachi, Richard Bwana; Ating'a, John Ernest

    2016-10-01

    To determine the difference in infection rate between 24h versus five days of prophylactic antibiotic use in management of Gustilo II open tibia fractures. Unblinded randomized control trial. Accident and Emergency, orthopedic wards and outpatient clinics at Kenyatta National Hospital (KNH). The study involved patients aged 18-80 years admitted through accident and emergency department with Gustilo II traumatic open tibia fractures. Patients were randomized into either 24hour or five day group and antibiotics started for 24hours or five days after surgical debridement. The wounds were exposed and scored using ASEPSIS wound scoring system for infection after 48h, 5days and at 14days. The main outcomes of interest were presence of infection at days 2, 5 and 14 and effect of duration to antibiotic administration on infection rate. There was no significant difference in infection rates between 24-hour and 5-day groups with infection rates of 23% (9/40) vs. 19% (7/37) respectively (p=0.699). The infection rate was significantly associated with time lapsed before administration of antibiotics (p=0.004). In the use of prophylactic antibiotics for the management of Gustilo II traumatic open tibia fractures, there is no difference in infection rate between 24hours and five days regimen but time to antibiotic administration correlates with infection rate. Antibiotic use for 24hours only has proven adequate prophylaxis against infection. This is underlined in our study which we hope shall inform practice in our setting. A larger, more appropriately controlled study would be useful. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. 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.

  16. 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 ...

  17. 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…

  18. 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...

  19. Randomized Controlled Trial Comparing Open Versus Laparoscopic Placement of a Peritoneal Dialysis Catheter and Outcomes: The CAPD I Trial.

    Science.gov (United States)

    van Laanen, Jorinde H H; Cornelis, Tom; Mees, Barend M; Litjens, Elisabeth J; van Loon, Magda M; Tordoir, Jan H M; Peppelenbosch, Arnoud G

    2018-01-01

    had a paramedian wound infection. In the laparoscopic group, 1 patient had a transient cardiac event, 1 patient had intraabdominal bleeding requiring reoperation, and 1 patient had fluid leakage that could be managed conservatively. The survival curve demonstrated a good long-term function of PD. This randomized controlled trial (RCT) comparing open vs laparoscopic placement of PD catheters demonstrates equal clinical success rates between the 2 techniques. Advanced laparoscopic techniques such as catheter fixation techniques and omentopexy might further improve clinical outcome. Copyright © 2018 International Society for Peritoneal Dialysis.

  20. An Open-Label Pilot Study of Combined Augmentation With Creatine Monohydrate and 5-Hydroxytryptophan for Selective Serotonin Reuptake Inhibitor- or Serotonin-Norepinephrine Reuptake Inhibitor-Resistant Depression in Adult Women.

    Science.gov (United States)

    Kious, Brent M; Sabic, Hana; Sung, Young-Hoon; Kondo, Douglas G; Renshaw, Perry

    2017-10-01

    Many women with major depressive disorder (MDD) respond inadequately to standard treatments. Augmentation of conventional antidepressants with creatine monohydrate and 5-hydroxytryptophan (5-HTP) could correct deficits in serotonin production and brain bioenergetics associated with depression in women, yielding synergistic benefit. We describe an open-label study of 5-HTP and creatine augmentation in women with MDD who had failed selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) monotherapy. Fifteen women who were adequately adherent to an SSRI or SNRI and currently experiencing MDD, with a 17-item Hamilton Depression Rating Scale (HAM-D) score of 16 or higher, were treated with 5 g of creatine monohydrate daily and 100 mg of 5-HTP twice daily for 8 weeks, with 4 weeks of posttreatment follow-up. The primary outcome was change in mean HAM-D scores. Mean HAM-D scores declined from 18.9 (SD, 2.5) at pretreatment visits to 7.5 (SD, 4.4) (P creatine and 5-HTP may represent an effective augmentation strategy for women with SSRI- or SNRI-resistant depression. Given the limitations of this small, open-label trial, future study in randomized, placebo-controlled trials is warranted.

  1. 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.

  2. Controllable labelling of stem cells with a novel superparamagnetic iron oxide-loaded cationic nanovesicle for MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Ruo Mi; Zhang, Fang; Wen, Xue Hua; Shen, Jun [Sun Yat-Sen University, Department of Radiology, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong (China); Cao, Nuo; Wang, Yi Ru; Shuai, Xin Tao [Sun Yat-Sen University, BME Center, School of Chemistry and Chemical Engineering, Guangzhou (China)

    2012-11-15

    To investigate the feasibility of highly efficient and controllable stem cell labelling for cellular MRI. A new class of cationic, superparamagnetic iron oxide nanoparticle (SPION)-loaded nanovesicles was synthesised to label rat bone marrow mesenchymal stem cells without secondary transfection agents. The optimal labelling conditions and controllability were assessed, and the effect of labelling on cell viability, proliferation activity and multilineage differentiation was determined. In 18 rats, focal ischaemic cerebral injury was induced and the rats randomly injected with 1 x 10{sup 6} cells labelled with 0-, 8- or 20-mV nanovesicles (n = 6 each). In vivo MRI was performed to follow grafted cells in contralateral striata, and results were correlated with histology. Optimal cell labelling conditions involved a concentration of 3.15 {mu}g Fe/mL nanovesicles with 20-mV positive charge and 1-h incubation time. Labelling efficiency showed linear change with an increase in the electric potentials of nanovesicles. Labelling did not affect cell viability, proliferation activity or multilineage differentiation capacity. The distribution and migration of labelled cells could be detected by MRI. Histology confirmed that grafted cells retained the label and remained viable. Stem cells can be effectively and safely labelled with cationic, SPION-loaded nanovesicles in a controllable way for cellular MRI. (orig.)

  3. Rationale and study design of PROVHILO - a worldwide multicenter randomized controlled trial on protective ventilation during general anesthesia for open abdominal surgery.

    Science.gov (United States)

    Hemmes, Sabrine N T; Severgnini, Paolo; Jaber, Samir; Canet, Jaume; Wrigge, Hermann; Hiesmayr, Michael; Tschernko, Edda M; Hollmann, Markus W; Binnekade, Jan M; Hedenstierna, Göran; Putensen, Christian; de Abreu, Marcelo Gama; Pelosi, Paolo; Schultz, Marcus J

    2011-05-06

    Post-operative pulmonary complications add to the morbidity and mortality of surgical patients, in particular after general anesthesia >2 hours for abdominal surgery. Whether a protective mechanical ventilation strategy with higher levels of positive end-expiratory pressure (PEEP) and repeated recruitment maneuvers; the "open lung strategy", protects against post-operative pulmonary complications is uncertain. The present study aims at comparing a protective mechanical ventilation strategy with a conventional mechanical ventilation strategy during general anesthesia for abdominal non-laparoscopic surgery. The PROtective Ventilation using HIgh versus LOw positive end-expiratory pressure ("PROVHILO") trial is a worldwide investigator-initiated multicenter randomized controlled two-arm study. Nine hundred patients scheduled for non-laparoscopic abdominal surgery at high or intermediate risk for post-operative pulmonary complications are randomized to mechanical ventilation with the level of PEEP at 12 cmH(2)O with recruitment maneuvers (the lung-protective strategy) or mechanical ventilation with the level of PEEP at maximum 2 cmH(2)O without recruitment maneuvers (the conventional strategy). The primary endpoint is any post-operative pulmonary complication. The PROVHILO trial is the first randomized controlled trial powered to investigate whether an open lung mechanical ventilation strategy in short-term mechanical ventilation prevents against postoperative pulmonary complications. ISRCTN: ISRCTN70332574.

  4. 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.

  5. 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…

  6. Intermittent theta-burst transcranial magnetic stimulation for autism spectrum disorder: an open-label pilot study

    Directory of Open Access Journals (Sweden)

    Caio Abujadi

    2017-12-01

    Full Text Available Objective: Theta-burst stimulation (TBS modulates synaptic plasticity more efficiently than standard repetitive transcranial magnetic stimulation delivery and may be a promising modality for neuropsychiatric disorders such as autism spectrum disorder (ASD. At present there are few effective interventions for prefrontal cortex dysfunction in ASD. We report on an open-label, pilot study of intermittent TBS (iTBS to target executive function deficits and restricted, repetitive behaviors in male children and adolescents with ASD. Methods: Ten right-handed, male participants, aged 9-17 years with ASD were enrolled in an open-label trial of iTBS treatment. Fifteen sessions of neuronavigated iTBS at 100% motor threshold targeting the right dorsolateral prefrontal cortex were delivered over 3 weeks. Results: Parent report scores on the Repetitive Behavior Scale Revised and the Yale-Brown Obsessive Compulsive Scale demonstrated improvements with iTBS treatment. Participants demonstrated improvements in perseverative errors on the Wisconsin Card Sorting Test and total time for the Stroop test. The iTBS treatments were well tolerated with no serious adverse effects. Conclusion: These preliminary results suggest that further controlled interventional studies of iTBS for ASD are warranted.

  7. Intermittent theta-burst transcranial magnetic stimulation for autism spectrum disorder: an open-label pilot study.

    Science.gov (United States)

    Abujadi, Caio; Croarkin, Paul E; Bellini, Bianca B; Brentani, Helena; Marcolin, Marco A

    2017-12-11

    Theta-burst stimulation (TBS) modulates synaptic plasticity more efficiently than standard repetitive transcranial magnetic stimulation delivery and may be a promising modality for neuropsychiatric disorders such as autism spectrum disorder (ASD). At present there are few effective interventions for prefrontal cortex dysfunction in ASD. We report on an open-label, pilot study of intermittent TBS (iTBS) to target executive function deficits and restricted, repetitive behaviors in male children and adolescents with ASD. Ten right-handed, male participants, aged 9-17 years with ASD were enrolled in an open-label trial of iTBS treatment. Fifteen sessions of neuronavigated iTBS at 100% motor threshold targeting the right dorsolateral prefrontal cortex were delivered over 3 weeks. Parent report scores on the Repetitive Behavior Scale Revised and the Yale-Brown Obsessive Compulsive Scale demonstrated improvements with iTBS treatment. Participants demonstrated improvements in perseverative errors on the Wisconsin Card Sorting Test and total time for the Stroop test. The iTBS treatments were well tolerated with no serious adverse effects. These preliminary results suggest that further controlled interventional studies of iTBS for ASD are warranted.

  8. Holter-electrocardiogram-monitoring in patients with acute ischaemic stroke (Find-AFRANDOMISED): an open-label randomised controlled trial.

    Science.gov (United States)

    Wachter, Rolf; Gröschel, Klaus; Gelbrich, Götz; Hamann, Gerhard F; Kermer, Pawel; Liman, Jan; Seegers, Joachim; Wasser, Katrin; Schulte, Anna; Jürries, Falko; Messerschmid, Anna; Behnke, Nico; Gröschel, Sonja; Uphaus, Timo; Grings, Anne; Ibis, Tugba; Klimpe, Sven; Wagner-Heck, Michaela; Arnold, Magdalena; Protsenko, Evgeny; Heuschmann, Peter U; Conen, David; Weber-Krüger, Mark

    2017-04-01

    Atrial fibrillation is a major risk factor for recurrent ischaemic stroke, but often remains undiagnosed in patients who have had an acute ischaemic stroke. Enhanced and prolonged Holter-electrocardiogram-monitoring might increase detection of atrial fibrillation. We therefore investigated whether enhanced and prolonged rhythm monitoring was better for detection of atrial fibrillation than standard care procedures in patients with acute ischaemic stroke. Find-AF randomised is an open-label randomised study done at four centres in Germany. We recruited patients with acute ischaemic stroke (symptoms for 7 days or less) aged 60 years or older presenting with sinus rhythm and without history of atrial fibrillation. Patients were included irrespective of the suspected cause of stroke, unless they had a severe ipsilateral carotid or intracranial artery stenosis, which were the exclusion criteria. We used a computer-generated allocation sequence to randomly assign patients in a 1:1 ratio with permuted block sizes of 2, 4, 6, and 8, stratified by centre, to enhanced and prolonged monitoring (ie, 10-day Holter-electrocardiogram [ECG]-monitoring at baseline, and at 3 months and 6 months of follow-up) or standard care procedures (ie, at least 24 h of rhythm monitoring). Participants and study physicians were not masked to group assignment, but the expert committees that adjudicated endpoints were. The primary endpoint was the occurrence of atrial fibrillation or atrial flutter (30 sec or longer) within 6 months after randomisation and before stroke recurrence. Because Holter ECG is a widely used procedure and not known to harm patients, we chose not to assess safety in detail. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01855035. Between May 8, 2013, and Aug 31, 2014, we recruited 398 patients. 200 patients were randomly assigned to the enhanced and prolonged monitoring group and 198 to the standard care group. After 6

  9. 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

  10. An open-label, pragmatic, randomized controlled clinical trial to evaluate the comparative effectiveness of daptomycin versus vancomycin for the treatment of complicated skin and skin structure infection.

    Science.gov (United States)

    Kauf, Teresa L; McKinnon, Peggy; Corey, G Ralph; Bedolla, John; Riska, Paul F; Sims, Matthew; Jauregui-Peredo, Luis; Friedman, Bruce; Hoehns, James D; Mercier, Renée-Claude; Garcia-Diaz, Julia; Brenneman, Susan K; Ng, David; Lodise, Thomas

    2015-11-07

    Treatment of complicated skin and skin structure infection (cSSSI) places a tremendous burden on the health care system. Understanding relative resource utilization associated with different antimicrobials is important for decision making by patients, health care providers, and payers. The authors conducted an open-label, pragmatic, randomized (1:1) clinical study (N = 250) to compare the effectiveness of daptomycin with that of vancomycin for treatment of patients hospitalized with cSSSI caused by suspected or documented methicillin-resistant Staphylococcus aureus infection. The primary study end point was infection-related length of stay (IRLOS). Secondary end points included health care resource utilization, cost, clinical response, and patient-reported outcomes. Patient assessments were performed daily until the end of antibiotic therapy or until hospital discharge, and at 14 days and 30 days after discharge. No difference was found for IRLOS, total LOS, and total inpatient cost between cohorts. Hospital LOS contributed 85.9% to the total hospitalization cost, compared with 6.4% for drug costs. Daptomycin showed a nonsignificant trend toward a higher clinical success rate, compared with vancomycin, at treatment days 2 and 3. In the multivariate analyses, vancomycin was associated with a lower likelihood of day 2 clinical success (odds ratio [OR] = 0.498, 95% confidence interval [CI], 0.249-0.997; P < 0.05). This study did not provide conclusive evidence of the superiority of one treatment over the other in terms of clinical, economic, or patient outcomes. The data suggest that physician and patient preference, rather than drug acquisition cost, should be the primary driver of initial antibiotic selection for hospitalized patients with cSSSI. ClinicalTrials.gov: NCT01419184 (Date: August 16, 2011).

  11. 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.

  12. 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.

  13. 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).

  14. 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

  15. 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

  16. 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]).

  17. Rationale and study design of PROVHILO - a worldwide multicenter randomized controlled trial on protective ventilation during general anesthesia for open abdominal surgery

    Directory of Open Access Journals (Sweden)

    Hedenstierna Göran

    2011-05-01

    Full Text Available Abstract Background Post-operative pulmonary complications add to the morbidity and mortality of surgical patients, in particular after general anesthesia >2 hours for abdominal surgery. Whether a protective mechanical ventilation strategy with higher levels of positive end-expiratory pressure (PEEP and repeated recruitment maneuvers; the "open lung strategy", protects against post-operative pulmonary complications is uncertain. The present study aims at comparing a protective mechanical ventilation strategy with a conventional mechanical ventilation strategy during general anesthesia for abdominal non-laparoscopic surgery. Methods The PROtective Ventilation using HIgh versus LOw positive end-expiratory pressure ("PROVHILO" trial is a worldwide investigator-initiated multicenter randomized controlled two-arm study. Nine hundred patients scheduled for non-laparoscopic abdominal surgery at high or intermediate risk for post-operative pulmonary complications are randomized to mechanical ventilation with the level of PEEP at 12 cmH2O with recruitment maneuvers (the lung-protective strategy or mechanical ventilation with the level of PEEP at maximum 2 cmH2O without recruitment maneuvers (the conventional strategy. The primary endpoint is any post-operative pulmonary complication. Discussion The PROVHILO trial is the first randomized controlled trial powered to investigate whether an open lung mechanical ventilation strategy in short-term mechanical ventilation prevents against postoperative pulmonary complications. Trial registration ISRCTN: ISRCTN70332574

  18. The efficacy of N-acetylcysteine as an adjunctive treatment in bipolar depression: an open label trial.

    Science.gov (United States)

    Berk, Michael; Dean, Olivia; Cotton, Sue M; Gama, Clarissa S; Kapczinski, Flavio; Fernandes, Brisa S; Kohlmann, Kristy; Jeavons, Susan; Hewitt, Karen; Allwang, Christine; Cobb, Heidi; Bush, Ashley I; Schapkaitz, Ian; Dodd, Seetal; Malhi, Gin S

    2011-12-01

    Evidence is accumulating to support the presence of redox dysregulation in a number of psychiatric disorders, including bipolar disorder. This dysregulation may be amenable to therapeutic intervention. Glutathione is the predominant non-enzymatic intracellular free radical scavenger in the brain, and the most generic of all endogenous antioxidants in terms of action. N-acetylcysteine (NAC) is a glutathione precursor that effectively replenishes brain glutathione. Given the failure of almost all modern trials of antidepressants in bipolar disorder to demonstrate efficacy, and the limited efficacy of mood stabilisers in the depressive phase of the disorder, this is a major unmet need. This study reports data on the treatment of 149 individuals with moderate depression during the 2 month open label phase of a randomised placebo controlled clinical trial of the efficacy of 1g BID of NAC that examined the use of NAC as a maintenance treatment for bipolar disorder. In this trial, the estimated mean baseline Bipolar Depression Rating Scale (BDRS) score was 19.7 (SE=0.8), and the mean BDRS score at the end of the 8 week open label treatment phase was 11.1 (SE=0.8). This reduction was statistically significant (pdepression scores with NAC treatment. Large placebo controlled trials of acute bipolar depression are warranted. Copyright © 2011 Elsevier B.V. All rights reserved.

  19. [Randomized controlled trial on the effectiveness of Corpitolinol 60 in the prevention of pressure sores in patients undergoing surgery].

    Science.gov (United States)

    Chiari, Paolo; Giorgi, Sabina; Ugolini, Daniela; Montanari, Morena; Giudanella, Pietro; Gramantieri, Antonella; Collesi, Franca; Pau, Michelina; Smaldone, Maddalena; Matarasso, Maddalena; Mazzini, Cinzia; Russo, Francesca; Gazineo, Domenica; Fontana, Mirella; Taddia, Patrizia

    2012-01-01

    Randomized controlled trial on the effectiveness of Corpitolinol 60 in the prevention of pressure sores in surgical patients. The risk of pressure sores in surgical patients is widely recognised. The Corpitolinol 60 (Sanyréne®) applied on compressed areas seems to reduce the risk of pressure sores. To assess the efficacy of Corpitolinol 60 in preventing pressure sores in the operatory theatre. The open label randomized clinical trial was conducted in 5 operating theatres of Northen Italy. Patients were randomized to receive Corpitolinol 60 in areas undergoing compression. Experimental group and controls were treated with usual measures for preventing pressure sores. The lesions were staged according to NPUAP up to 24 hours after surgery. Three-hundred-one patients were randomized (155 in the Sanyréne® group and 143 controls). The main variables predictive of pressure sores risk (ASA class, sex, age, duration of the surgery, and BMI) were comparable across groups. At the end of the surgery 71 patients (23.8%) in the experimental group and 47 controls (30.8%) had a pressure sore (p 0.006; RR 1.81 IC95% 1.17-2.79). Twelve and 24 hours after surgery the differences between groups were not significant. The aim of reducing pressure sores was not reached for patients treated with Corpitolinol 60.

  20. 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.

  1. Nimotuzumab plus chemotherapy versus chemotherapy alone in advanced non-small-cell lung cancer: a multicenter, randomized, open-label Phase II study

    Directory of Open Access Journals (Sweden)

    Babu KG

    2014-06-01

    Full Text Available K Govind Babu,1 Kumar Prabhash,2 Ashok K Vaid,3 Bhawna Sirohi,3 Ravi B Diwakar,4 Raghunadha Rao,5 Madhuchanda Kar,6 Hemant Malhotra,7 Shona Nag,8 Chanchal Goswami,9 Vinod Raina,10 Ravi Mohan111Kidwai Memorial Institute of Oncology, Bangalore, 2Tata Memorial Hospital, Mumbai, 3Artemis Health Institute, Delhi, 4Bangalore Institute of Oncology, Bangalore, 5Nizam Institute of Medical Sciences, Hyderabad, 6B R Singh Hospital, Kolkata, 7Birla Cancer Centre, Jaipur, 8Jehangir Hospital, Pune, 9B P Poddar Hospital and Medical Research Ltd, Kolkata, 10Institute Rotary Cancer Hospital, New Delhi, 11King George Hospital, Visakhapatnam, IndiaBackground: The purpose of this study was to evaluate the safety and efficacy of nimotuzumab in combination with chemotherapy (docetaxel and carboplatin versus chemotherapy alone in patients with stage IIIB/IV non-small-cell lung cancer.Methods: This multicenter, open-label, Phase II study randomized 110 patients to receive nimotuzumab plus chemotherapy (nimotuzumab group or chemotherapy alone (control group, and comprised concomitant, maintenance, and follow-up phases. Nimotuzumab 200 mg was administered once weekly for 13 weeks during the first two phases with four cycles of chemotherapy and docetaxel 75 mg/m2 and carboplatin (area under the curve 5 mg/mL*min every 3 weeks for a maximum of four cycles during the concomitant phase. The primary endpoint was objective response rate (sum of complete response and partial response. Secondary endpoints, ie, overall survival and progression-free survival, were estimated using the Kaplan–Meier method. Efficacy was evaluated on the intent-to-treat and efficacy-evaluable sets. Safety was assessed from adverse event and serious adverse event data.Results: The objective response rate was significantly higher in the nimotuzumab group than in the control group in the intent-to-treat population (54% versus 34.5%; P=0.04. A complete response and partial response were achieved in 3

  2. Neo-adjuvant chemotherapy followed by chemoradiation and surgery with and without cetuximab in patients with resectable esophageal cancer: a randomized, open-label, phase III trial (SAKK 75/08).

    Science.gov (United States)

    Ruhstaller, T; Thuss-Patience, P; Hayoz, S; Schacher, S; Knorrenschild, J R; Schnider, A; Plasswilm, L; Budach, W; Eisterer, W; Hawle, H; Mariette, C; Hess, V; Mingrone, W; Montemurro, M; Girschikofsky, M; Schmidt, S C; Bitzer, M; Bedenne, L; Brauchli, P; Stahl, M

    2018-04-04

    This open-label, phase lll trial compared chemoradiation followed by surgery with or without neoadjuvant and adjuvant cetuximab in patients with resectable esophageal carcinoma. Patients were randomly assigned (1:1) to 2 cycles of chemotherapy (docetaxel 75 mg/m2, cisplatin 75 mg/m2) followed by chemoradiation (45 Gy, docetaxel 20 mg/m2 and cisplatin 25 mg/m2, weekly for 5 weeks) and surgery, with or without neoadjuvant cetuximab 250 mg/m2 weekly and adjuvant cetuximab 500 mg/m2 fortnightly for 3 months. The primary endpoint was progression-free survival (PFS). In total, 300 patients (median age, 61 years; 88% male; 63% adenocarcinoma; 85% cT3/4a, 90% cN+) were assigned to cetuximab (n = 149) or control (n = 151). The R0-resection rate was 95% for cetuximab versus 97% for control. Postoperative treatment-related mortality was 6% in both arms. Median PFS was 2.9 years (95% CI, 2.0 to not reached) with cetuximab and 2.0 years (95% CI, 1.5 to 2.8) with control (HR, 0.79; 95% CI, 0.58 to 1.07; P = .13). Median overall survival (OS) time was 5.1 years (95% CI, 3.7 to not reached) versus 3.0 years (95% CI, 2.2 to 4.2) for cetuximab and control, respectively (HR, 0.73; 95% CI, 0.52 to 1.01; P = .055). Time to loco-regional failure after R0-resection was significantly longer for cetuximab (HR 0.53; 95% CI, 0.31 to 0.90; P = .017); time to distant failure did not differ between arms (HR, 1.01; 95% CI, 0.64 to 1.59, P = .97). Cetuximab did not increase adverse events in neoadjuvant or postoperative settings. Adding cetuximab to multimodal therapy significantly improved loco-regional control, and led to clinically relevant, but not-significant improvements in PFS and OS in resectable esophageal carcinoma. NCT01107639.

  3. 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.

  4. An Open-Label, Multicenter Observational Study for Patients with Alzheimer’s Disease Treated with Memantine in the Clinical Practice

    Directory of Open Access Journals (Sweden)

    S.S. Stamouli

    2011-01-01

    Full Text Available Background/Aims: In this post-marketing observational study, the safety and effectiveness of memantine were evaluated in patients with Alzheimer’s disease (AD. Methods: In a 6-month, observational, open-label study at 202 specialist sites in Greece, the effectiveness of memantine was evaluated using the Mini-Mental State Examination (MMSE and the Instrumental Activities of Daily Living (IADL scale at baseline, and after 3 and 6 months. Discontinuation rates and adverse drug reactions (ADRs were also recorded to evaluate the safety profile of memantine. Results: 2,570 patients participated in the study. Three and 6 months after baseline, MMSE and IADL scores were significantly improved compared to baseline. At the end of the study, 67% of the patients had improved their MMSE score; 7.1% of the patients reported ≧1 ADRs, and treatment was discontinued due to ADR in 0.7%. Conclusion: Memantine was well tolerated and had a positive effect on the patient’s cognitive and functional ability in real-life clinical practice, in agreement with randomized, controlled trials.

  5. 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

  6. 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

  7. 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.

  8. Home parenteral nutrition increases fat free mass in patients with incurable gastrointestinal cancer. Results of a randomized controlled trial

    DEFF Research Database (Denmark)

    Obling, Sine Roelsgaard; Wilson, Benedicte Vibjerg; Pfeiffer, Per

    2018-01-01

    , the primary endpoint being fat free mass (FFM) and secondary: muscle function, quality of life and overall survival. Design and methods: In a single centre open-label randomised controlled trial, patients with incurable gastrointestinal cancer, nutritionally at risk, were randomly assigned to either; a) best...... FFM. Secondary outcomes were muscle strength, quality of life and survival. Results: Eligible for inclusion were 234 patients, 47 of these accepted enrolment; 25 were randomized to non-sHPN and 22 to sHPN according to performance status, age and diagnoses. Median age was 66.9 (41.5-88.2), BMI 21.3 (14.......8-35.7) and (91%) were receiving palliative chemotherapy. Median FFM and fat free mass index increased in the sHPN group. At 12 weeks a significant difference (p FFM. Handgrip strength increased in both groups...

  9. Honest, Open, Proud for adolescents with mental illness: pilot randomized controlled trial.

    Science.gov (United States)

    Mulfinger, Nadine; Müller, Sabine; Böge, Isabel; Sakar, Vehbi; Corrigan, Patrick W; Evans-Lacko, Sara; Nehf, Luise; Djamali, Julia; Samarelli, Anna; Kempter, Michael; Ruckes, Christian; Libal, Gerhard; Oexle, Nathalie; Noterdaeme, Michele; Rüsch, Nicolas

    2018-06-01

    Due to public stigma or self-stigma and shame, many adolescents with mental illness (MI) struggle with the decision whether to disclose their MI to others. Both disclosure and nondisclosure are associated with risks and benefits. Honest, Open, Proud (HOP) is a peer-led group program that supports participants with disclosure decisions in order to reduce stigma's impact. Previously, HOP had only been evaluated among adults with MI. This two-arm pilot randomized controlled trial included 98 adolescents with MI. Participants were randomly assigned to HOP and treatment as usual (TAU) or to TAU alone. Outcomes were assessed pre (T0/baseline), post (T1/after the HOP program), and at 3-week follow-up (T2/6 weeks after T0). Primary endpoints were stigma stress at T1 and quality of life at T2. Secondary outcomes included self-stigma, disclosure-related distress, empowerment, help-seeking intentions, recovery, and depressive symptoms. The trial is registered on ClinicalTrials (NCT02751229; http://www.clinicaltrials.gov). Compared to TAU, adolescents in the HOP program showed significantly reduced stigma stress at T1 (d = .92, p self-stigma, disclosure-related distress, secrecy, help-seeking intentions, attitudes to disclosure, recovery, and depressive symptoms. Effects at T1 remained stable or improved further at follow-up. In a limited economic evaluation HOP was cost-efficient in relation to gains in quality of life. As HOP is a compact three-session program and showed positive effects on stigma and disclosure variables as well as on symptoms and quality of life, it could help to reduce stigma's negative impact among adolescents with MI. © 2017 Association for Child and Adolescent Mental Health.

  10. 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.

  11. Efficacy of Folic Acid Supplementation in Autistic Children Participating in Structured Teaching: An Open-Label Trial.

    Science.gov (United States)

    Sun, Caihong; Zou, Mingyang; Zhao, Dong; Xia, Wei; Wu, Lijie

    2016-06-07

    Autism spectrum disorders (ASD) are recognized as a major public health issue. Here, we evaluated the effects of folic acid intervention on methylation cycles and oxidative stress in autistic children enrolled in structured teaching. Sixty-six autistic children enrolled in this open-label trial and participated in three months of structured teaching. Forty-four children were treated with 400 μg folic acid (two times/daily) for a period of three months during their structured teaching (intervention group), while the remaining 22 children were not given any supplement for the duration of the study (control group). The Autism Treatment Evaluation Checklist (ATEC) and Psychoeducational Profile-third edition (PEP-3) were measured at the beginning and end of the treatment period. Folic acid, homocysteine, and glutathione metabolism in plasma were measured before and after treatment in 29 autistic children randomly selected from the intervention group and were compared with 29 age-matched unaffected children (typical developmental group). The results illustrated folic acid intervention improved autism symptoms towards sociability, cognitive verbal/preverbal, receptive language, and affective expression and communication. Furthermore, this treatment also improved the concentrations of folic acid, homocysteine, and normalized glutathione redox metabolism. Folic acid supplementation may have a certain role in the treatment of children with autism.

  12. 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....

  13. Effect of homeopathy on analgesic intake following knee ligament reconstruction: a phase III monocentre randomized placebo controlled study

    Science.gov (United States)

    Paris, A; Gonnet, N; Chaussard, C; Belon, P; Rocourt, F; Saragaglia, D; Cracowski, J L

    2008-01-01

    Aims The efficacy of homeopathy is still under debate. The objective of this study was to assess the efficacy of homeopathic treatment (Arnica montana 5 CH, Bryonia alba 5 CH, Hypericum perforatum 5 CH and Ruta graveolens 3 DH) on cumulated morphine intake delivered by PCA over 24 h after knee ligament reconstruction. Methods This was an add-on randomized controlled study with three parallel groups: a double-blind homeopathic or placebo arm and an open-label noninterventional control arm. Eligible patients were 18–60 years old candidates for surgery of the anterior cruciate ligament. Treatment was administered the evening before surgery and continued for 3 days. The primary end-point was cumulated morphine intake delivered by PCA during the first 24 h inferior or superior/equal to 10 mg day−1. Results One hundred and fifty-eight patients were randomized (66 in the placebo arm, 67 in the homeopathic arm and 25 in the noninterventional group). There was no difference between the treated and the placebo group for primary end-point (mean (95% CI) 48% (35.8, 56.3), and 56% (43.7, 68.3), required less than 10 mg day−1 of morphine in each group, respectively). The homeopathy treatment had no effect on morphine intake between 24 and 72 h or on the visual analogue pain scale, or on quality of life assessed by the SF-36 questionnaire. In addition, these parameters were not different in patients enrolled in the open-label noninterventional control arm. Conclusions The complex of homeopathy tested in this study was not superior to placebo in reducing 24 h morphine consumption after knee ligament reconstruction. What is already known about this subject The efficacy of homeopathy is still under debate and a recent meta-analysis recommended further randomized double-blind clinical trials to identify any clinical situation in which homeopathy might be effective. What this study adds The complex of homeopathy tested in this study (Arnica montana 5 CH, Bryonia alba 5 CH

  14. 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.

  15. Defibrotide for prophylaxis of hepatic veno-occlusive disease in paediatric haemopoietic stem-cell transplantation: an open-label, phase 3, randomised controlled trial.

    Science.gov (United States)

    Corbacioglu, Selim; Cesaro, Simone; Faraci, Maura; Valteau-Couanet, Dominique; Gruhn, Bernd; Rovelli, Attilio; Boelens, Jaap J; Hewitt, Annette; Schrum, Johanna; Schulz, Ansgar S; Müller, Ingo; Stein, Jerry; Wynn, Robert; Greil, Johann; Sykora, Karl-Walter; Matthes-Martin, Susanne; Führer, Monika; O'Meara, Anne; Toporski, Jacek; Sedlacek, Petr; Schlegel, Paul G; Ehlert, Karoline; Fasth, Anders; Winiarski, Jacek; Arvidson, Johan; Mauz-Körholz, Christine; Ozsahin, Hulya; Schrauder, Andre; Bader, Peter; Massaro, Joseph; D'Agostino, Ralph; Hoyle, Margaret; Iacobelli, Massimo; Debatin, Klaus-Michael; Peters, Christina; Dini, Giorgio

    2012-04-07

    Hepatic veno-occlusive disease is a leading cause of morbidity and mortality after haemopoietic stem-cell transplantation (HSCT). We aimed to assess whether defibrotide can reduce the incidence of veno-occlusive disease in this setting. In our phase 3 open-label, randomised controlled trial, we enrolled patients at 28 European university hospitals or academic medical centres. Eligible patients were younger than 18 years, had undergone myeloablative conditioning before allogeneic or autologous HSCT, and had one or more risk factor for veno-occlusive disease based on modified Seattle criteria. We centrally assigned eligible participants on the basis of a computer-generated randomisation sequence (1:1), stratified by centre and presence of osteopetrosis, to receive intravenous defibrotide prophylaxis (treatment group) or not (control group). The primary endpoint was incidence of veno-occlusive disease by 30 days after HSCT, adjudicated by a masked, independent review committee, in eligible patients who consented to randomisation (intention-to-treat population), and was assessed with a competing risk approach. Patients in either group who developed veno-occlusive disease received defibrotide for treatment. We assessed adverse events to 180 days after HSCT in all patients who received allocated prophylaxis. This trial is registered with ClinicalTrials.gov, number NCT00272948. Between Jan 25, 2006, and Jan 29, 2009, we enrolled 356 eligible patients to the intention-to-treat population. 22 (12%) of 180 patients randomly allocated to the defibrotide group had veno-occlusive disease by 30 days after HSCT compared with 35 (20%) of 176 controls (risk difference -7·7%, 95% CI -15·3 to -0·1; Z test for competing risk analysis p=0·0488; log-rank test p=0·0507). 154 (87%) of 177 patients in the defibrotide group had adverse events by day 180 compared with 155 (88%) of 176 controls. Defibrotide prophylaxis seems to reduce incidence of veno-occlusive disease and is well

  16. 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....

  17. Normothermic versus hypothermic cardiopulmonary bypass in children undergoing open heart surgery (thermic-2): study protocol for a randomized controlled trial.

    Science.gov (United States)

    Baos, Sarah; Sheehan, Karen; Culliford, Lucy; Pike, Katie; Ellis, Lucy; Parry, Andrew J; Stoica, Serban; Ghorbel, Mohamed T; Caputo, Massimo; Rogers, Chris A

    2015-05-25

    During open heart surgery, patients are connected to a heart-lung bypass machine that pumps blood around the body ("perfusion") while the heart is stopped. Typically the blood is cooled during this procedure ("hypothermia") and warmed to normal body temperature once the operation has been completed. The main rationale for "whole body cooling" is to protect organs such as the brain, kidneys, lungs, and heart from injury during bypass by reducing the body's metabolic rate and decreasing oxygen consumption. However, hypothermic perfusion also has disadvantages that can contribute toward an extended postoperative hospital stay. Research in adults and small randomized controlled trials in children suggest some benefits to keeping the blood at normal body temperature throughout surgery ("normothermia"). However, the two techniques have not been extensively compared in children. The Thermic-2 study will test the hypothesis that the whole body inflammatory response to the nonphysiological bypass and its detrimental effects on different organ functions may be attenuated by maintaining the body at 35°C-37°C (normothermic) rather than 28°C (hypothermic) during pediatric complex open heart surgery. This is a single-center, randomized controlled trial comparing the effectiveness and acceptability of normothermic versus hypothermic bypass in 141 children with congenital heart disease undergoing open heart surgery. Children having scheduled surgery to repair a heart defect not requiring deep hypothermic circulatory arrest represent the target study population. The co-primary clinical outcomes are duration of inotropic support, intubation time, and postoperative hospital stay. Secondary outcomes are in-hospital mortality and morbidity, blood loss and transfusion requirements, pre- and post-operative echocardiographic findings, routine blood gas and blood test results, renal function, cerebral function, regional oxygen saturation of blood in the cerebral cortex, assessment of

  18. Prospective open-label study of add-on and monotherapy topiramate in civilians with chronic nonhallucinatory posttraumatic stress disorder

    Directory of Open Access Journals (Sweden)

    Berlant Jeffrey L

    2004-08-01

    Full Text Available Abstract Background In order to confirm therapeutic effects of topiramate on posttraumatic stress disorder (PTSD observed in a prior study, a new prospective, open-label study was conducted to examine acute responses in chronic, nonhallucinatory PTSD. Methods Thirty-three consecutive newly recruited civilian adult outpatients (mean age 46 years, 85% female with DSM-IV-diagnosed chronic PTSD, excluding those with concurrent auditory or visual hallucinations, received topiramate either as monotherapy (n = 5 or augmentation (n = 28. The primary measure was a change in the PTSD Checklist-Civilian Version (PCL-C score from baseline to 4 weeks, with response defined as a ≥ 30% reduction of PTSD symptoms. Results For those taking the PCL-C at both baseline and week 4 (n = 30, total symptoms declined by 49% at week 4 (paired t-test, P Conclusions Promising open-label findings in a new sample converge with findings of a previous study. The use of topiramate for treatment of chronic PTSD, at least in civilians, warrants controlled clinical trials.

  19. 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

  20. 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…

  1. Adding left atrial appendage closure to open heart surgery provides protection from ischemic brain injury six years after surgery independently of atrial fibrillation history: the LAACS randomized study.

    Science.gov (United States)

    Park-Hansen, Jesper; Holme, Susanne J V; Irmukhamedov, Akhmadjon; Carranza, Christian L; Greve, Anders M; Al-Farra, Gina; Riis, Robert G C; Nilsson, Brian; Clausen, Johan S R; Nørskov, Anne S; Kruuse, Christina R; Rostrup, Egill; Dominguez, Helena

    2018-05-23

    Open heart surgery is associated with high occurrence of atrial fibrillation (AF), subsequently increasing the risk of post-operative ischemic stroke. Concomitant with open heart surgery, a cardiac ablation procedure is commonly performed in patients with known AF, often followed by left atrial appendage closure with surgery (LAACS). However, the protective effect of LAACS on the risk of cerebral ischemia following cardiac surgery remains controversial. We have studied whether LAACS in addition to open heart surgery protects against post-operative ischemic brain injury regardless of a previous AF diagnosis. One hundred eighty-seven patients scheduled for open heart surgery were enrolled in a prospective, open-label clinical trial and randomized to concomitant LAACS vs. standard care. Randomization was stratified by usage of oral anticoagulation (OAC) planned to last at least 3 months after surgery. The primary endpoint was a composite of post-operative symptomatic ischemic stroke, transient ischemic attack or imaging findings of silent cerebral ischemic (SCI) lesions. During a mean follow-up of 3.7 years, 14 (16%) primary events occurred among patients receiving standard surgery vs. 5 (5%) in the group randomized to additional LAACS (hazard ratio 0.3; 95% CI: 0.1-0.8, p = 0.02). In per protocol analysis (n = 141), 14 (18%) primary events occurred in the control group vs. 4 (6%) in the LAACS group (hazard ratio 0.3; 95% CI: 0.1-1.0, p = 0.05). In a real-world setting, LAACS in addition to elective open-heart surgery was associated with lower risk of post-operative ischemic brain injury. The protective effect was not conditional on AF/OAC status at baseline. LAACS study, clinicaltrials.gov NCT02378116 , March 4th 2015, retrospectively registered.

  2. Open-Lung Ventilation Improves Clinical Outcomes in Off-Pump Coronary Artery Bypass Surgery: A Randomized Controlled Trial.

    Science.gov (United States)

    Bolzan, Douglas W; Trimer, Renata; Begot, Isis; Nasrala, Mara L S; Forestieri, Patricia; Mendez, Vanessa M F; Arena, Ross; Gomes, Walter J; Guizilini, Solange

    2016-06-01

    To compare pulmonary function, functional capacity, and clinical outcomes among conventional mechanical ventilation (CMV), early open-lung (EOL), and late open-lung (LOL) strategies after off-pump coronary artery bypass surgery (OPCAB). Prospective, randomized, and double-blinded study. Two hospitals of the Federal University of Sao Paulo, Brazil. Ninety-three patients undergoing elective first-time OPCAB. Patients were randomized into 3 groups: CMV (n=31); LOL (n=32) initiated upon intensive care unit (ICU) arrival; EOL (n = 30) initiated after intubation. Spirometry was performed at bedside preoperatively and on postoperative days (PODs) 1, 3, and 5. Partial pressure of arterial oxygen (PaO2) and pulmonary shunt fraction were evaluated presurgically and on POD 1; 6-minute walk test (6MWT) was performed presurgically and on POD 5. Both open-lung groups demonstrated higher forced vital capacity and forced expiratory volume in 1 second on PODs 1, 3 and 5 compared to the CMV group (pLOL groups were compared. Both open-lung strategies were able to promote higher pulmonary function preservation and greater recovery of functional capacity with better clinical outcomes after OPCAB. No difference in outcome was found when comparing initiation of OLS intraoperatively or after ICU arrival. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. 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

  4. CO2 driven endotracheal tube cuff control in critically ill patients: A randomized controlled study.

    Science.gov (United States)

    De Pascale, Gennaro; Pennisi, Mariano Alberto; Vallecoccia, Maria Sole; Bello, Giuseppe; Maviglia, Riccardo; Montini, Luca; Di Gravio, Valentina; Cutuli, Salvatore Lucio; Conti, Giorgio; Antonelli, Massimo

    2017-01-01

    To determine the safety and clinical efficacy of an innovative integrated airway system (AnapnoGuard™ 100 system) that continuously monitors and controls the cuff pressure (Pcuff), while facilitating the aspiration of subglottic secretions (SS). This was a prospective, single centre, open-label, randomized, controlled feasibility and safety trial. The primary endpoint of the study was the rate of device related adverse events (AE) and serious AE (SAE) as a result of using AnapnoGuard (AG) 100 during mechanical ventilation. Secondary endpoints were: (1) mechanical complications rate (2) ICU staff satisfaction; (3) VAP occurrence; (4) length of mechanical ventilation; (5) length of Intensive Care Unit stay and mortality; (6) volume of evacuated subglottic secretions. Sixty patients were randomized to be intubated with the AG endotracheal-tube (ETT) and connected to the AG 100 system allowing Pcuff adjustment and SS aspiration; or with an ETT combined with SS drainage and Pcuff controlled manually. No difference in adverse events rate was identified between the groups. The use of AG system was associated with a significantly higher incidence of Pcuff determinations in the safety range (97.3% vs. 71%; paspirated SS secretions: (192.0[64-413] ml vs. 150[50-200], p = 0.19 (total)); (57.8[20-88.7] ml vs. 50[18.7-62] ml, p = 0.11 (daily)). No inter-group difference was detected using AG system vs. controls in terms of post-extubation throat pain level (0 [0-2] vs. 0 [0-3]; p = 0.7), hoarseness (42.9% vs. 75%; p = 0.55) and tracheal mucosa oedema (16.7% vs. 10%; p = 0.65). Patients enrolled in the AG group had a trend to reduced VAP risk of ventilator-associated pneumonia(VAP) (14.8% vs. 40%; p = 0.06), which were more frequently monomicrobial (25% vs. 70%; p = 0.03). No statistically significant difference was observed in duration of mechanical ventilation, ICU stay, and mortality. The use AG 100 system and AG tube in critically ill intubated patients is safe and

  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. Social Norms and Financial Incentives to Promote Employees’ Healthy Food Choices: A Randomized Controlled Trial

    Science.gov (United States)

    Thorndike, Anne N.; Riis, Jason; Levy, Douglas E.

    2016-01-01

    Population-level strategies to improve healthy food choices are needed for obesity prevention. We conducted a randomized controlled trial of 2,672 employees at Massachusetts General Hospital who were regular customers of the hospital cafeteria with all items labeled green (healthy), yellow (less healthy), or red (unhealthy) to determine if social norm (peer-comparison) feedback with or without financial incentives increased employees’ healthy food choices. Participants were randomized in 2012 to three arms: 1) monthly letter with social norm feedback about healthy food purchases, comparing employee to “all” and to “healthiest” customers (feedback-only); 2) monthly letter with social norm feedback plus small financial incentive for increasing green purchases (feedback-incentive); or 3) no contact (control). The main outcome was change in proportion of green-labeled purchases at end of 3-month intervention. Post-hoc analyses examined linear trends. At baseline, the proportion of green-labeled purchases (50%) did not differ between arms. At end of the 3-month intervention, the percentage increase in green-labeled purchases was larger in the feedback-incentive arm compared to control (2.2% vs. 0.1%, P=0.03), but the two intervention arms were not different. The rate of increase in green-labeled purchases was higher in both feedback-only (P=0.04) and feedback-incentive arms (P=0.004) compared to control. At end of a 3-month wash-out, there were no differences between control and intervention arms. Social norms plus small financial incentives increased employees’ healthy food choices over the short-term. Future research will be needed to assess the impact of this relatively low-cost intervention on employees’ food choices and weight over the long-term. Trial Registration: Clinical Trials.gov NCT01604499 PMID:26827617

  7. 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.

  8. 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

  9. Aerobic training for improved memory in patients with stress-related exhaustion: a randomized controlled trial.

    Science.gov (United States)

    Eskilsson, Therese; Slunga Järvholm, Lisbeth; Malmberg Gavelin, Hanna; Stigsdotter Neely, Anna; Boraxbekk, Carl-Johan

    2017-09-02

    Patients with stress-related exhaustion suffer from cognitive impairments, which often remain after psychological treatment or work place interventions. It is important to find effective treatments that can address this problem. Therefore, the aim of this study was to investigate the effects on cognitive performance and psychological variables of a 12-week aerobic training program performed at a moderate-vigorous intensity for patients with exhaustion disorder who participated in a multimodal rehabilitation program. In this open-label, parallel, randomized and controlled trial, 88 patients diagnosed with exhaustion disorder participated in a 24-week multimodal rehabilitation program. After 12 weeks in the program the patients were randomized to either a 12-week aerobic training intervention or to a control group with no additional training. Primary outcome measure was cognitive function, and secondary outcome measures were psychological health variables and aerobic capacity. In total, 51% patients in the aerobic training group and 78% patients in the control group completed the intervention period. The aerobic training group significantly improved in maximal oxygen uptake and episodic memory performance. No additional improvement in burnout, depression or anxiety was observed in the aerobic group compared with controls. Aerobic training at a moderate-vigorous intensity within a multimodal rehabilitation program for patients with exhaustion disorder facilitated episodic memory. A future challenge would be the clinical implementation of aerobic training and methods to increase feasibility in this patient group. ClinicalTrials.gov: NCT03073772 . Retrospectively registered 21 February 2017.

  10. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial.

    Science.gov (United States)

    Weber, Jeffrey S; D'Angelo, Sandra P; Minor, David; Hodi, F Stephen; Gutzmer, Ralf; Neyns, Bart; Hoeller, Christoph; Khushalani, Nikhil I; Miller, Wilson H; Lao, Christopher D; Linette, Gerald P; Thomas, Luc; Lorigan, Paul; Grossmann, Kenneth F; Hassel, Jessica C; Maio, Michele; Sznol, Mario; Ascierto, Paolo A; Mohr, Peter; Chmielowski, Bartosz; Bryce, Alan; Svane, Inge M; Grob, Jean-Jacques; Krackhardt, Angela M; Horak, Christine; Lambert, Alexandre; Yang, Arvin S; Larkin, James

    2015-04-01

    Nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, can result in durable responses in patients with melanoma who have progressed after ipilimumab and BRAF inhibitors. We assessed the efficacy and safety of nivolumab compared with investigator's choice of chemotherapy (ICC) as a second-line or later-line treatment in patients with advanced melanoma. In this randomised, controlled, open-label, phase 3 trial, we recruited patients at 90 sites in 14 countries. Eligible patients were 18 years or older, had unresectable or metastatic melanoma, and progressed after ipilimumab, or ipilimumab and a BRAF inhibitor if they were BRAF(V 600) mutation-positive. Participating investigators randomly assigned (with an interactive voice response system) patients 2:1 to receive an intravenous infusion of nivolumab 3 mg/kg every 2 weeks or ICC (dacarbazine 1000 mg/m(2) every 3 weeks or paclitaxel 175 mg/m(2) combined with carboplatin area under the curve 6 every 3 weeks) until progression or unacceptable toxic effects. We stratified randomisation by BRAF mutation status, tumour expression of PD-L1, and previous best overall response to ipilimumab. We used permuted blocks (block size of six) within each stratum. Primary endpoints were the proportion of patients who had an objective response and overall survival. Treatment was given open-label, but those doing tumour assessments were masked to treatment assignment. We assessed objective responses per-protocol after 120 patients had been treated with nivolumab and had a minimum follow-up of 24 weeks, and safety in all patients who had had at least one dose of treatment. The trial is closed and this is the first interim analysis, reporting the objective response primary endpoint. This study is registered with ClinicalTrials.gov, number NCT01721746. Between Dec 21, 2012, and Jan 10, 2014, we screened 631 patients, randomly allocating 272 patients to nivolumab and 133 to ICC. Confirmed objective responses were reported

  11. 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.

  12. Randomized control trial for the assessment of the anti-albuminuric effects of topiroxostat in hyperuricemic patients with diabetic nephropathy (the ETUDE study).

    Science.gov (United States)

    Kato, Sawako; Ando, Masahiko; Mizukoshi, Toshihiro; Nagata, Takanobu; Katsuno, Takayuki; Kosugi, Tomoki; Tsuboi, Naotake; Maruyama, Shoichi

    2016-05-01

    Proteinuria is an established risk factor for diabetic nephropathy. Recent studies indicate that some xanthine oxidase inhibitors have a renoprotective effect. The aim of this study was to assess whether topiroxostat reduces albuminuria in hyperuricemic patients with diabetic nephropathy and overt proteinuria. The ETUDE study is an ongoing 24-week, multicenter, open-label, randomized (1:1), parallel group study involving hyperuricemic patients with diabetic nephropathy (estimated glomerular filtration rate [eGFR] ≥ 20 mL/min/1.73 m(2)) and overt proteinuria (0.3 ≤ urine protein to creatinine ratio (UPCR) ETUDE trial is the first randomized controlled study of topiroxostat in hyperuricemic patients with diabetic nephropathy and overt proteinuria. We will clarify the pleiotropic function of topiroxostat including an anti-albumiuric effect as well as its effects on safely decreasing serum uric acid levels.

  13. Scheduled Intermittent Screening with Rapid Diagnostic Tests and Treatment with Dihydroartemisinin-Piperaquine versus Intermittent Preventive Therapy with Sulfadoxine-Pyrimethamine for Malaria in Pregnancy in Malawi: An Open-Label Randomized Controlled Trial.

    Directory of Open Access Journals (Sweden)

    Mwayiwawo Madanitsa

    2016-09-01

    Full Text Available In Africa, most plasmodium infections during pregnancy remain asymptomatic, yet are associated with maternal anemia and low birthweight. WHO recommends intermittent preventive therapy in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP. However, sulfadoxine-pyrimethamine (SP efficacy is threatened by high-level parasite resistance. We conducted a trial to evaluate the efficacy and safety of scheduled intermittent screening with malaria rapid diagnostic tests (RDTs and treatment of RDT-positive women with dihydroartemisinin-piperaquine (DP as an alternative strategy to IPTp-SP.This was an open-label, two-arm individually randomized superiority trial among HIV-seronegative women at three sites in Malawi with high SP resistance. The intervention consisted of three or four scheduled visits in the second and third trimester, 4 to 6 wk apart. Women in the IPTp-SP arm received SP at each visit. Women in the intermittent screening and treatment in pregnancy with DP (ISTp-DP arm were screened for malaria at every visit and treated with DP if RDT-positive. The primary outcomes were adverse live birth outcome (composite of small for gestational age, low birthweight [<2,500 g], or preterm birth [<37 wk] in paucigravidae (first or second pregnancy and maternal or placental plasmodium infection at delivery in multigravidae (third pregnancy or higher. Analysis was by intention to treat. Between 21 July 2011 and 18 March 2013, 1,873 women were recruited (1,155 paucigravidae and 718 multigravidae. The prevalence of adverse live birth outcome was similar in the ISTp-DP (29.9% and IPTp-SP (28.8% arms (risk difference = 1.08% [95% CI -3.25% to 5.41%]; all women: relative risk [RR] = 1.04 [95% CI 0.90-1.20], p = 0.625; paucigravidae: RR = 1.10 [95% CI 0.92-1.31], p = 0.282; multigravidae: RR = 0.92 [95% CI 0.71-1.20], p = 0.543. The prevalence of malaria at delivery was higher in the ISTp-DP arm (48.7% versus 40.8%; risk difference = 7.85%, [95% CI 3

  14. 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…

  15. Induction of labour versus expectant monitoring for gestational hypertension or mild pre-eclampsia after 36 weeks' gestation (HYPITAT): a multicentre, open-label randomised controlled trial.

    Science.gov (United States)

    Koopmans, Corine M; Bijlenga, Denise; Groen, Henk; Vijgen, Sylvia M C; Aarnoudse, Jan G; Bekedam, Dick J; van den Berg, Paul P; de Boer, Karin; Burggraaff, Jan M; Bloemenkamp, Kitty W M; Drogtrop, Addy P; Franx, Arie; de Groot, Christianne J M; Huisjes, Anjoke J M; Kwee, Anneke; van Loon, Aren J; Lub, Annemiek; Papatsonis, Dimitri N M; van der Post, Joris A M; Roumen, Frans J M E; Scheepers, Hubertina C J; Willekes, Christine; Mol, Ben W J; van Pampus, Maria G

    2009-09-19

    Robust evidence to direct management of pregnant women with mild hypertensive disease at term is scarce. We investigated whether induction of labour in women with a singleton pregnancy complicated by gestational hypertension or mild pre-eclampsia reduces severe maternal morbidity. We undertook a multicentre, parallel, open-label randomised controlled trial in six academic and 32 non-academic hospitals in the Netherlands between October, 2005, and March, 2008. We enrolled patients with a singleton pregnancy at 36-41 weeks' gestation, and who had gestational hypertension or mild pre-eclampsia. Participants were randomly allocated in a 1:1 ratio by block randomisation with a web-based application system to receive either induction of labour or expectant monitoring. Masking of intervention allocation was not possible. The primary outcome was a composite measure of poor maternal outcome--maternal mortality, maternal morbidity (eclampsia, HELLP syndrome, pulmonary oedema, thromboembolic disease, and placental abruption), progression to severe hypertension or proteinuria, and major post-partum haemorrhage (>1000 mL blood loss). Analysis was by intention to treat and treatment effect is presented as relative risk. This study is registered, number ISRCTN08132825. 756 patients were allocated to receive induction of labour (n=377 patients) or expectant monitoring (n=379). 397 patients refused randomisation but authorised use of their medical records. Of women who were randomised, 117 (31%) allocated to induction of labour developed poor maternal outcome compared with 166 (44%) allocated to expectant monitoring (relative risk 0.71, 95% CI 0.59-0.86, phypertensive disease beyond 37 weeks' gestation. ZonMw.

  16. Adding fast‐acting insulin aspart to basal insulin significantly improved glycaemic control in patients with type 2 diabetes: A randomized, 18‐week, open‐label, phase 3 trial (onset 3)

    OpenAIRE

    Rodbard, Helena W.; Tripathy, Devjit; Vidrio Velázquez, Maricela; Demissie, Marek; Tamer, Søren C.; Piletič, Milivoj

    2017-01-01

    Aim To confirm glycaemic control superiority of mealtime fast‐acting insulin aspart (faster aspart) in a basal–bolus (BB) regimen vs basal‐only insulin. Materials and methods In this open‐label, randomized, 18‐week trial (51 sites; 6 countries), adults (n = 236) with inadequately controlled type 2 diabetes (T2D; mean glycosylated haemoglobin [HbA1c] ± SD: 7.9% ± 0.7% [63.1 ± 7.5 mmol/mol]) receiving basal insulin and oral antidiabetic drugs underwent 8‐week optimization of prior once‐daily ba...

  17. Long-term tolerability and maintenance of therapeutic response to sodium oxybate in an open-label extension study in patients with fibromyalgia.

    Science.gov (United States)

    Spaeth, Michael; Alegre, Cayetano; Perrot, Serge; Wang, Youyu; Guinta, Diane R; Alvarez-Horine, Sarah; Russell, Irwin

    2013-11-11

    The long-term safety and therapeutic response of sodium oxybate (SXB) in fibromyalgia syndrome (FM) patients were assessed for a combined period of up to 1 year in a prospective, multicenter, open-label, extension study in patients completing 1 of 2 phase 3 randomized, double-blind, controlled, 14-week trials that examined the efficacy and safety of SXB 4.5 g, SXB 6 g, and placebo for treatment of FM. This extension study comprised an additional 38 weeks of treatment and was carried out at 130 clinical sites in 7 countries. Initial entry criteria for the previous 2 double-blind clinical trials required that patients aged ≥ 18 years met the American College of Rheumatology 1990 criteria for FM, had a body mass index (BMI) Fibromyalgia Impact Questionnaire (FIQ) total scores, and other measures. Responder analyses showed that 68.8% of patients achieved ≥ 30% reduction in pain VAS and 69.7% achieved ≥ 30% reduction in FIQ total score at study endpoint. The long-term safety profile of SXB in FM patients was similar to that in the previously reported controlled clinical trials. Improvement in pain and other FM clinical domains was maintained during long-term use. ClinicalTrials.gov NCT00423605.

  18. Long-term tolerability and maintenance of therapeutic response to sodium oxybate in an open-label extension study in patients with fibromyalgia

    Science.gov (United States)

    2013-01-01

    Introduction The long-term safety and therapeutic response of sodium oxybate (SXB) in fibromyalgia syndrome (FM) patients were assessed for a combined period of up to 1 year in a prospective, multicenter, open-label, extension study in patients completing 1 of 2 phase 3 randomized, double-blind, controlled, 14-week trials that examined the efficacy and safety of SXB 4.5 g, SXB 6 g, and placebo for treatment of FM. Methods This extension study comprised an additional 38 weeks of treatment and was carried out at 130 clinical sites in 7 countries. Initial entry criteria for the previous 2 double-blind clinical trials required that patients aged ≥ 18 years met the American College of Rheumatology 1990 criteria for FM, had a body mass index (BMI) Fibromyalgia Impact Questionnaire (FIQ) total scores, and other measures. Responder analyses showed that 68.8% of patients achieved ≥ 30% reduction in pain VAS and 69.7% achieved ≥ 30% reduction in FIQ total score at study endpoint. Conclusions The long-term safety profile of SXB in FM patients was similar to that in the previously reported controlled clinical trials. Improvement in pain and other FM clinical domains was maintained during long-term use. Trial registration ClinicalTrials.gov NCT00423605. PMID:24286114

  19. 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.

  20. 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.

  1. 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

  2. Randomized, open-label, 5-way crossover study to evaluate the pharmacokinetic/pharmacodynamic interaction between furosemide and the non-steroidal anti-inflammatory drugs diclofenac and ibuprofen in healthy volunteers.

    Science.gov (United States)

    Paterson, C A; Jacobs, D; Rasmussen, S; Youngberg, S P; McGuinness, N

    2011-08-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) can induce renal complications in patients taking loop diuretics. This study investigated the pharmacokinetic/pharmacodynamic effects and safety profile of orally administered diclofenac sodium, ibuprofen and diclofenac epolamine topical patch (DETP) on furosemide in healthy adult subjects. This open-label, randomized, 5-way crossover study was conducted in 40 subjects (aged 19 - 45 y). Diclofenac (75 mg taken orally twice daily), DETP (1.3% applied topically twice daily), or ibuprofen (800 mg taken orally thrice daily) was administered for 3 consecutive days, followed by co-administration with furosemide (given intravenously as 20 mg/2 min). Plasma furosemide and NSAID concentrations, urine furosemide, sodium and potassium concentrations and urine output were determined throughout the 24 h period following furosemide administration. Orally administered ibuprofen significantly increased furosemide AUC(0-t) (37%) and AUC(0-inf) (36%) and decreased total body CL (27%), R(max) (19%) and CLR (23%) geometric mean ratios compared with furosemide control. Oral and topical diclofenac had no pharmacokinetic effects on furosemide. Ibuprofen increased sodium excretion (Ae(0-24), 16%) and decreased sodium R(max) (15%), and oral diclofenac decreased urine output (Vu(0-24), 15%). DETP had no effect on furosemide pharmacodynamics; total systemic exposure to diclofenac during DETP treatment was diclofenac. Treatments were generally safe, with 25 subjects reporting a total of 112 adverse events. Pharmacodynamic effects were seen with oral diclofenac (urine output) and ibuprofen (urine sodium excretion). Furosemide also affected plasma and urine pharmacokinetic profiles. Pharmacologic effects of DETP on furosemide were not observed under these conditions. Additional research is warranted to delineate the potential interactions of other NSAIDs with furosemide and other loop diuretics.

  3. Randomized controlled trial for assessment of Internet of Things system to guide intensive glucose control in diabetes outpatients: Nagoya Health Navigator Study protocol.

    Science.gov (United States)

    Onoue, Takeshi; Goto, Motomitsu; Kobayashi, Tomoko; Tominaga, Takashi; Ando, Masahiko; Honda, Hiroyuki; Yoshida, Yasuko; Tosaki, Takahiro; Yokoi, Hisashi; Kato, Sawako; Maruyama, Shoichi; Arima, Hiroshi

    2017-08-01

    The Internet of Things (IoT) allows collecting vast amounts of health-relevant data such as daily activity, body weight (BW), and blood pressure (BP) automatically. The use of IoT devices to monitor diabetic patients has been studied, but could not evaluate IoT-dependent effects because health data were not measured in control groups. This multicenter, open-label, randomized, parallel group study will compare the impact of intensive health guidance using IoT and conventional medical guidance on glucose control. It will be conducted in outpatients with type 2 diabetes for a period of 6 months. IoT devices to measure amount of daily activity, BW, and BP will be provided to IoT group patients. Healthcare professionals (HCPs) will provide appropriate feedback according to the data. Non-IoT control, patients will be given measurement devices that do not have a feedback function. The primary outcome is glycated hemoglobin at 6 months. The study has already enrolled 101 patients, 50 in the IoT group and 51 in the non-IoT group, at the two participating outpatient clinics. The baseline characteristics of two groups did not differ, except for triglycerides. This will be the first randomized, controlled study to evaluate IoT-dependent effects of intensive feedback from HCPs. The results will validate a new method of health-data collection and provision of feedback suitable for diabetes support with increased effectiveness and low cost.

  4. Insulin glulisine compared to insulin aspart and to insulin lispro administered by continuous subcutaneous insulin infusion in patients with type 1 diabetes: a randomized controlled trial

    NARCIS (Netherlands)

    van Bon, Arianne C.; Bode, Bruce W.; Sert-Langeron, Caroline; DeVries, J. Hans; Charpentier, Guillaume

    2011-01-01

    In a previous pilot study comparing insulin glulisine (GLU) with insulin aspart (ASP) administered by continuous subcutaneous insulin infusion (CSII), GLU-treated patients did show a trend toward fewer catheter occlusions compared with ASP-treated patients. Here we performed a randomized open-label,

  5. 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

  6. Young patients with type 1 diabetes poorly controlled and poorly compliant with self-monitoring of blood glucose: can technology help? Results of the i-NewTrend randomized clinical trial.

    Science.gov (United States)

    Di Bartolo, Paolo; Nicolucci, Antonio; Cherubini, Valentino; Iafusco, Diario; Scardapane, Marco; Rossi, Maria Chiara

    2017-04-01

    To compare iBGStar™ + DMApp (experimental meter + telemedicine system) (iBGStar) with a traditional glucose meter (Control) in type 1 diabetes adolescents/young adults. i-NewTrend was a multicenter, open-label, randomized trial involving subjects aged 14-24 years, on basal-bolus insulin, HbA1c ≥ 8.0%, and poorly compliant with SMBG (i.e., technologies effective and acceptable to patients is an option to improve adherence to diabetes care. The trial was registered at ClinicalTrials.gov (registration number NCT02073188).

  7. Adaptive servo-ventilation therapy for patients with chronic heart failure in a confirmatory, multicenter, randomized, controlled study.

    Science.gov (United States)

    Momomura, Shin-Ichi; Seino, Yoshihiko; Kihara, Yasuki; Adachi, Hitoshi; Yasumura, Yoshio; Yokoyama, Hiroyuki; Wada, Hiroshi; Ise, Takayuki; Tanaka, Koichi

    2015-01-01

    Adaptive servo-ventilation (ASV) therapy is expected to be novel nonpharmacotherapy with hemodynamic effects on patients with chronic heart failure (CHF), but sufficient evidence has not been obtained. A 24-week, open-label, randomized, controlled study was performed to confirm the cardiac function-improving effect of ASV therapy on CHF patients. At 39 institutions, 213 outpatients with CHF, whose left ventricular ejection fraction (LVEF) was control group], respectively. The primary endpoint was LVEF, and the secondary endpoints were HF deterioration, B-type natriuretic peptide (BNP), and clinical composite response (CCR: NYHA class+HF deterioration). LVEF and BNP improved significantly at completion against the baseline values in the 2 groups. However, no significant difference was found between these groups. HF deterioration tended to be suppressed. The ASV group showed a significant improvement in CCR corroborated by significant improvements in NYHA class and ADL against the control group. Under the present study's conditions, ASV therapy was not superior to GDMT in the cardiac function-improving effect but showed a clinical status-improving effect, thus indicating a given level of clinical benefit.

  8. Sage tea-thyme-peppermint hydrosol oral rinse reduces chemotherapy-induced oral mucositis: A randomized controlled pilot study.

    Science.gov (United States)

    Mutluay Yayla, Ezgi; Izgu, Nur; Ozdemir, Leyla; Aslan Erdem, Sinem; Kartal, Murat

    2016-08-01

    This pilot study aimed to investigate the preventive effect of sage tea-thyme-peppermint hydrosol oral rinse used in conjunction with basic oral care on chemotherapy-induced oral mucositis. An open-label randomized controlled study. Two oncology hospitals in Ankara, Turkey. Patients receiving 5-fluorouracil-based chemotherapy regimens were divided into the intervention group (N=30) and control group (N=30). Basic oral care was prescribed to the control group, while the intervention group was prescribed sage tea-thyme-peppermint hydrosol in addition to basic oral care. All patients were called to assess their compliance with the study instructions on day 5 and 14. Oral mucositis was evaluated using an inspection method or by assessing oral cavity photos based on the World Health Organization oral toxicity scale on day 5 and 14. Most of the patients in the intervention group did not develop oral mucositis on day 5. In addition, the incidence of grade 1 oral mucositis was statistically lower in the intervention group (10%) than the control group (53.3%) on day 5. By day 14, the majority of patients in both the groups had grade 0 oral mucositis. Sage tea-thyme-peppermint hydrosol oral rinse has promising results in alleviating oral mucositis. This hydrosol can be recommended for clinical use as it is well tolerated and cost-effective. However, further randomized controlled trials are needed to support the study. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. 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.

  10. Quality control of labelled compounds

    International Nuclear Information System (INIS)

    Matucha, M.

    1979-01-01

    Some advantages and disadvantages of methods used for quality control of organic labelled compounds (1 31 I, 14 C) are shortly discussed. The methods used are electrophoresis, ultraviolet and infrared spectrometry, radiogas and thin-layer chromatography. (author)

  11. Morphine versus Nalbuphine for Open Gynaecological Surgery: A Randomized Controlled Double Blinded Trial

    Directory of Open Access Journals (Sweden)

    Shiv Akshat

    2014-01-01

    Full Text Available Introduction. Pain is the commonest morbidity after open surgical procedures. The most effective treatment of postoperative pain is opioid therapy. Morphine, the commonly used opioid, is associated with many side effects including respiratory depression, sedation, postoperative nausea vomiting, and pruritus. Nalbuphine, on the other hand, is known to cause less respiratory depression. Thus this study was undertaken to compare the intraoperative and postoperative analgesic efficacy and side effect profile of the two drugs. Methodology. 60 patients undergoing open gynaecological surgery were randomized to receive either morphine (Group M or nalbuphine (Group N in the intraoperative and postoperative period. Intraoperative analgesic efficacy (measured by need for rescue analgesics, postoperative pain by visual analogue scale, and side effects like postoperative nausea, vomiting, sedation, respiratory depression, and pruritus were compared in both groups. Intraoperative and postoperative heart rate and blood pressure were also compared between the groups. Results. Need for intraoperative analgesia was significantly more in Group N (P=0.023. Postoperative VAS scores were significantly different between the groups at various time points; however, none of the patients required any rescue analgesia. The incidence of various side effects was not significantly different between the groups. The haemodynamic profile of patients was comparable between the groups in both intraoperative and postoperative period. Conclusion. Nalbuphine provides less effective intraoperative analgesia than morphine in patients undergoing open gynaecological surgery under general anaesthesia. Both drugs, however, provided similar postoperative analgesia and had similar haemodynamic and side effect profile.

  12. Intensive perioperative glucose control does not improve outcomes of patients submitted to open-heart surgery: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Raquel Pei Chen Chan

    2009-01-01

    Full Text Available BACKGROUND: The objective of this study was to investigate the relationship between different target levels of glucose and the clinical outcomes of patients undergoing cardiac surgery with cardiopulmonary bypass. METHODS: We designed a prospective study in a university hospital where 109 consecutive patients were enrolled during a six-month period. All patients were scheduled for open-heart surgery requiring cardiopulmonary bypass. Patients were randomly allocated into two groups. One group consisted of 55 patients and had a target glucose level of 80-130 mg/dl, while the other contained 54 patients and had a target glucose level of 160-200 mg/dl. These parameters were controlled during surgery and for 36 hours after surgery in the intensive care unit. Primary outcomes were clinical outcomes, including time of mechanical ventilation, length of stay in the intensive care unit, infection, hypoglycemia, renal or neurological dysfunction, blood transfusion and length of stay in the hospital. The secondary outcome was a combined end-point (mortality at 30 days, infection or length of stay in the intensive care unit of more than 3 days. A p-value of 0.05. CONCLUSIONS: In 109 patients undergoing cardiac surgery with cardiopulmonary bypass, both protocols of glycemic control in an intraoperative setting and in the intensive care unit were found to be safe, easily achieved and not to differentially affect clinical outcomes.

  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. CO2 driven endotracheal tube cuff control in critically ill patients: A randomized controlled study.

    Directory of Open Access Journals (Sweden)

    Gennaro De Pascale

    Full Text Available To determine the safety and clinical efficacy of an innovative integrated airway system (AnapnoGuard™ 100 system that continuously monitors and controls the cuff pressure (Pcuff, while facilitating the aspiration of subglottic secretions (SS.This was a prospective, single centre, open-label, randomized, controlled feasibility and safety trial. The primary endpoint of the study was the rate of device related adverse events (AE and serious AE (SAE as a result of using AnapnoGuard (AG 100 during mechanical ventilation. Secondary endpoints were: (1 mechanical complications rate (2 ICU staff satisfaction; (3 VAP occurrence; (4 length of mechanical ventilation; (5 length of Intensive Care Unit stay and mortality; (6 volume of evacuated subglottic secretions. Sixty patients were randomized to be intubated with the AG endotracheal-tube (ETT and connected to the AG 100 system allowing Pcuff adjustment and SS aspiration; or with an ETT combined with SS drainage and Pcuff controlled manually.No difference in adverse events rate was identified between the groups. The use of AG system was associated with a significantly higher incidence of Pcuff determinations in the safety range (97.3% vs. 71%; p<0.01 and a trend to a greater volume of aspirated SS secretions: (192.0[64-413] ml vs. 150[50-200], p = 0.19 (total; (57.8[20-88.7] ml vs. 50[18.7-62] ml, p = 0.11 (daily. No inter-group difference was detected using AG system vs. controls in terms of post-extubation throat pain level (0 [0-2] vs. 0 [0-3]; p = 0.7, hoarseness (42.9% vs. 75%; p = 0.55 and tracheal mucosa oedema (16.7% vs. 10%; p = 0.65. Patients enrolled in the AG group had a trend to reduced VAP risk of ventilator-associated pneumonia(VAP (14.8% vs. 40%; p = 0.06, which were more frequently monomicrobial (25% vs. 70%; p = 0.03. No statistically significant difference was observed in duration of mechanical ventilation, ICU stay, and mortality.The use AG 100 system and AG tube in critically ill

  16. An open, randomized, parallel-group study to compare the efficacy and safety profile of inhaled human insulin (Exubera) with glibenclamide as adjunctive therapy in patients with type 2 diabetes poorly controlled on metformin

    DEFF Research Database (Denmark)

    Barnett, AH; Dreyer, M; Lange, Peter

    2006-01-01

    OBJECTIVE: To compare the efficacy and safety profile of adding inhaled human insulin (INH) (Exubera) or glibenclamide to metformin monotherapy in patients with poorly controlled type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted an open-label, parallel, 24-week multicenter trial. Patients...... associated clinical manifestations. CONCLUSIONS: In patients with type 2 diabetes poorly controlled on metformin, adding INH or glibenclamide was similarly effective in improving glycemic control, and both were well tolerated. A predefined subgroup with very high A1C (>9.5%) was more effectively treated...

  17. 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.

  18. Hippuran-123 I: labelling and quality control

    International Nuclear Information System (INIS)

    Barboza, M.F. de; Colturato, M.T.; Herrerias, R.; Muramoto, E.

    1992-01-01

    The o-iodo hippuric acid labelling with radioiodine is a radiopharmaceutical used with more frequently for evaluation the kidney function. Several reactive kits for labelling with 123 I are prepared. Controls of radiochemical purity and biological distribution are made. The reactive kit of hippuran is kept at 4 C during 2 years. (C.G.C.)

  19. Open-Label Randomized Trial of Titrated Disease Management for Patients with Hypertension: Study Design and Baseline Sample Characteristics

    Science.gov (United States)

    Jackson, George L.; Weinberger, Morris; Kirshner, Miriam A.; Stechuchak, Karen M.; Melnyk, Stephanie D.; Bosworth, Hayden B.; Coffman, Cynthia J.; Neelon, Brian; Van Houtven, Courtney; Gentry, Pamela W.; Morris, Isis J.; Rose, Cynthia M.; Taylor, Jennifer P.; May, Carrie L.; Han, Byungjoo; Wainwright, Christi; Alkon, Aviel; Powell, Lesa; Edelman, David

    2016-01-01

    Despite the availability of efficacious treatments, only half of patients with hypertension achieve adequate blood pressure (BP) control. This paper describes the protocol and baseline subject characteristics of a 2-arm, 18-month randomized clinical trial of titrated disease management (TDM) for patients with pharmaceutically-treated hypertension for whom systolic blood pressure (SBP) is not controlled (≥140mmHg for non-diabetic or ≥130mmHg for diabetic patients). The trial is being conducted among patients of four clinic locations associated with a Veterans Affairs Medical Center. An intervention arm has a TDM strategy in which patients' hypertension control at baseline, 6, and 12 months determines the resource intensity of disease management. Intensity levels include: a low-intensity strategy utilizing a licensed practical nurse to provide bi-monthly, non-tailored behavioral support calls to patients whose SBP comes under control; medium-intensity strategy utilizing a registered nurse to provide monthly tailored behavioral support telephone calls plus home BP monitoring; and high-intensity strategy utilizing a pharmacist to provide monthly tailored behavioral support telephone calls, home BP monitoring, and pharmacist-directed medication management. Control arm patients receive the low-intensity strategy regardless of BP control. The primary outcome is SBP. There are 385 randomized (192 intervention; 193 control) veterans that are predominately older (mean age 63.5 years) men (92.5%). 61.8% are African American, and the mean baseline SBP for all subjects is 143.6mmHg. This trial will determine if a disease management program that is titrated by matching the intensity of resources to patients' BP control leads to superior outcomes compared to a low-intensity management strategy. PMID:27417982

  20. Efficacy of the Ubiquitous Spaced Retrieval-based Memory Advancement and Rehabilitation Training (USMART) program among patients with mild cognitive impairment: a randomized controlled crossover trial.

    Science.gov (United States)

    Han, Ji Won; Son, Kyung Lak; Byun, Hye Jin; Ko, Ji Won; Kim, Kayoung; Hong, Jong Woo; Kim, Tae Hyun; Kim, Ki Woong

    2017-06-06

    Spaced retrieval training (SRT) is a nonpharmacological intervention for mild cognitive impairment (MCI) and dementia that trains the learning and retention of target information by recalling it over increasingly long intervals. We recently developed the Ubiquitous Spaced Retrieval-based Memory Advancement and Rehabilitation Training (USMART) program as a convenient, self-administered tablet-based SRT program. We also demonstrated the utility of USMART for improving memory in individuals with MCI through an open-label uncontrolled trial. This study had an open-label, single-blind, randomized, controlled, two-period crossover design. Fifty patients with MCI were randomized into USMART-usual care and usual care-USMART treatment sequences. USMART was completed or usual care was provided biweekly over a 4-week treatment period with a 2-week washout period between treatment periods. Primary outcome measures included the Word List Memory Test, Word List Recall Test (WLRT), and Word List Recognition Test. Outcomes were measured at baseline, week 5, and week 11 by raters who were blinded to intervention type. An intention-to-treat analysis and linear mixed modeling were used. Of 50 randomized participants, 41 completed the study (18% dropout rate). The USMART group had larger improvements in WLRT score (effect size = 0.49, p = 0.031) than the usual care group. There were no significant differences in other primary or secondary measures between the USMART and usual care groups. Moreover, no USMART-related adverse events were reported. The 4-week USMART modestly improved information retrieval in older people with MCI, and was well accepted with minimal technical support. ClinicalTrials.gov NCT01688128 . Registered 12 September 2012.

  1. 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.

  2. Glimepiride versus pioglitazone combination therapy in subjects with type 2 diabetes inadequately controlled on metformin monotherapy: results of a randomized clinical trial.

    Science.gov (United States)

    Umpierrez, Guillermo; Issa, Maher; Vlajnic, Aleksandra

    2006-04-01

    To compare the effect of add-on glimepiride or pioglitazone in subjects with type 2 diabetes inadequately controlled on metformin monotherapy. Multicenter, randomized, parallel-group, open-label, forcedtitration study involving 203 adults with poorly controlled type 2 diabetes (A1C 7.5-10%) on metformin monotherapy. Subjects were randomized to receive glimepiride or pioglitazone, titrated to the maximum dose for 26 weeks. Subjects were evaluated for A1C changes, fasting plasma glucose (FPG), insulin, C-peptide, and lipid levels. Safety outcomes and diabetes-related healthcare resource utilization were also evaluated. Both treatment groups achieved similar and significant mean decreases from baseline to endpoint (week 26) in A1C (p = 0.0001) and FPG (p use of fasting C-peptide concentration > or = 0.27 nmol/L in the inclusion criteria was a potential limitation as it may have included those patients with an improved probability for glimepiride or pioglitazone response. In addition, a larger patient population would have provided a greater degree of data applicability. In patients with type 2 diabetes inadequately controlled on metformin monotherapy, add-on glimepiride or pioglitazone results in similar overall improvements in glycemic control. Compared with pioglitazone, glimepiride is associated with faster glycemic control, lower total and LDL cholesterol levels and reduced short-term healthcare costs.

  3. 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

  4. Do nutrition labels influence healthier food choices? Analysis of label viewing behaviour and subsequent food purchases in a labelling intervention trial.

    Science.gov (United States)

    Ni Mhurchu, Cliona; Eyles, Helen; Jiang, Yannan; Blakely, Tony

    2018-02-01

    There are few objective data on how nutrition labels are used in real-world shopping situations, or how they affect dietary choices and patterns. The Starlight study was a four-week randomised, controlled trial of the effects of three different types of nutrition labels on consumer food purchases: Traffic Light Labels, Health Star Rating labels, or Nutrition Information Panels (control). Smartphone technology allowed participants to scan barcodes of packaged foods and receive randomly allocated labels on their phone screen, and to record their food purchases. The study app therefore provided objectively recorded data on label viewing behaviour and food purchases over a four-week period. A post-hoc analysis of trial data was undertaken to assess frequency of label use, label use by food group, and association between label use and the healthiness of packaged food products purchased. Over the four-week intervention, study participants (n = 1255) viewed nutrition labels for and/or purchased 66,915 barcoded packaged products. Labels were viewed for 23% of all purchased products, with decreasing frequency over time. Shoppers were most likely to view labels for convenience foods, cereals, snack foods, bread and bakery products, and oils. They were least likely to view labels for sugar and honey products, eggs, fish, fruit and vegetables, and meat. Products for which participants viewed the label and subsequently purchased the product during the same shopping episode were significantly healthier than products where labels were viewed but the product was not subsequently purchased: mean difference in nutrient profile score -0.90 (95% CI -1.54 to -0.26). In a secondary analysis of a nutrition labelling intervention trial, there was a significant association between label use and the healthiness of products purchased. Nutrition label use may therefore lead to healthier food purchases. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. Moxibustion for pain relief in patients with primary dysmenorrhea: A randomized controlled trial.

    Science.gov (United States)

    Yang, Mingxiao; Chen, Xiangzhu; Bo, Linna; Lao, Lixing; Chen, Jiao; Yu, Siyi; Yu, Zheng; Tang, Hongzhi; Yi, Ling; Wu, Xi; Yang, Jie; Liang, Fanrong

    2017-01-01

    Though moxibustion is frequently used to treat primary dysmenorrhea in China, relevant evidence supporting its effectiveness is still scanty. This study was a pragmatic randomized, conventional drug controlled, open-labeled clinical trial. After initial screen, 152 eligible participants were averagely randomized to receive two different treatment strategies: Moxibustion and conventional drugs. Participants and practitioners were not blinded in this study. The duration of each treatment was 3 months. The primary outcome was pain relief measured by the Visual Analogue Scale. The menstrual pain severity was recorded in a menstrual pain diary. 152 eligible patients were included but only 133 of them eventually completed the whole treatment course. The results showed that the menstrual pain intensity in experimental group and control group was reduced from 6.38±1.28 and 6.41±1.29, respectively, at baseline, to 2.54±1.41 and 2.47±1.29 after treatment. The pain reduction was not significantly different between these two groups (P = 0.76), however; the pain intensity was significantly reduced relative to baseline for each group (Ppain-related symptoms. The serum levels of pain mediators, such as PGF2α, OT, vWF, β-EP, PGE2, were significantly improved after treatment in both groups (Ppain, given their treatment effects and economic costs. This study as a pragmatic trial only demonstrates the effectiveness, not the efficacy, of moxibustion for menstrual pain. It can't rule out the effect of psychological factors during treatment process, because no blind procedure or sham control was used due to availability. In clinical practice, moxibustion should be used at the discretion of patients and their physicians. ClinialTrials.gov NCT01972906.

  6. 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.

  7. Periodontal treatment to improve glycaemic control in diabetic patients: study protocol of the randomized, controlled DIAPERIO trial.

    Science.gov (United States)

    Vergnes, Jean-Noel; Arrivé, Elise; Gourdy, Pierre; Hanaire, Hélène; Rigalleau, Vincent; Gin, Henri; Sédarat, Cyril; Dorignac, Georges; Bou, Christophe; Sixou, Michel; Nabet, Cathy

    2009-08-02

    Periodontitis is a common, chronic inflammatory disease caused by gram-negative bacteria leading to destruction of tissues supporting the teeth. Epidemiological studies have consistently shown increased frequency, extent and severity of periodontitis among diabetic adults. More recently, some controlled clinical trials have also suggested that periodontal treatment could improve glycaemic control in diabetic patients. However current evidence does not provide sufficient information on which to confidently base any clinical recommendations. The main objective of this clinical trial is to assess whether periodontal treatment could lead to a decrease in glycated haemoglobin levels in metabolically unbalanced diabetic patients suffering from chronic periodontitis. The DIAPERIO trial is an open-label, 13-week follow-up, randomized, controlled trial. The total target sample size is planned at 150 participants, with a balanced (1:1) treatment allocation (immediate treatment vs delayed treatment). Periodontal treatment will include full mouth non-surgical scaling and root planing, systemic antibiotherapy, local antiseptics (chlorhexidine 0.12%) and oral health instructions. The primary outcome will be the difference in change of HbA1c between the two groups after the 13-weeks' follow-up. Secondary outcomes will be the difference in change of fructosamine levels and quality of life between the two groups. The DIAPERIO trial will provide insight into the question of whether periodontal treatment could lead to an improvement in glycaemic control in metabolically unbalanced diabetic patients suffering from periodontitis. The results of this trial will help to provide evidence-based recommendations for clinicians and a draft framework for designing national health policies. Current Controlled Trials ISRCTN15334496.

  8. Therapeutic Benefit of Smoked Cannabis in Randomized Placebo-Controlled Studies.

    Science.gov (United States)

    Bowen, Lynneice L; McRae-Clark, Aimee L

    2018-01-01

    The medicinal use of marijuana has been legalized in 28 states, with a wide range of specificity for approved medical conditions. Even with the emergence of non-combustion-based delivery systems, 90% of marijuana users in 2014 used smoked marijuana. This review summarizes the data available on the use of smoked marijuana for medical purposes. A literature search was performed to retrieve randomized controlled trials exploring the efficacy of smoked cannabis for treatment of a medical condition. Studies with the primary end point listed as the effect of smoked cannabis on a disease-specific characteristic were included. Open-label studies and studies using other administration methods were excluded. Seven studies met these criteria and were included in this review. Cannabis did not outperform placebo on experimentally evoked pain or the timed walk test. Clear evidence indicates that smoked cannabis reduces intraocular pressure, but the effect is too brief (less than 4 hrs) to be of therapeutic benefit for this chronic disorder. Consistent evidence also showed that smoked marijuana, even at lower concentrations of tetrahydrocannabinol, increased total daily calorie intake and number of eating occasions. Neither of the studies with quality of life as secondary outcome measures revealed statistically significantly improved outcomes with cannabis use. © 2017 Pharmacotherapy Publications, Inc.

  9. 21 CFR 1271.250 - Labeling controls.

    Science.gov (United States)

    2010-04-01

    ..., AND CELLULAR AND TISSUE-BASED PRODUCTS Current Good Tissue Practice § 1271.250 Labeling controls. (a... available for distribution is accompanied by documentation of the donor eligibility determination as...

  10. Effectiveness of Vitamin D Supplement Therapy in Chronic Stable Schizophrenic Male Patients: A Randomized Controlled Trial.

    Science.gov (United States)

    Sheikhmoonesi, Fatemeh; Zarghami, Mehran; Mamashli, Shima; Yazdani Charati, Jamshid; Hamzehpour, Romina; Fattahi, Samineh; Azadbakht, Rahil; Kashi, Zahra; Ala, Shahram; Moshayedi, Mona; Alinia, Habibollah; Hendouei, Narjes

    2016-01-01

    In this study, the aim was to determine whether adding vitamin D to the standard therapeutic regimen of schizophrenic male patients with inadequate vitamin D status could improve some aspects of the symptom burden or not. This study was an open parallel label randomized clinical trial. Eighty patients with chronic stable schizophrenia with residual symptoms and Vitamin D deficiency were recruited randomly and then received either 600000 IU Vitamin D injection once along with their antipsychotic regimen or with their antipsychotic regimen only. Serum vitamin D was measured twice: first at the baseline and again on the fourth month. Positive and Negative Syndrome Scale (PANSS) was assessed at the baseline and on the fourth month. During the study, the vitamin D serum changes in vitamin group and control group were 22.1 ± 19.9(95%CI = 15.9-28.8) and 0.2 ± 1.7(95%CI = 0.2-0.8) (ng/mL) (pvitamin D and control group respectively (p=0.5). The changes of PANSS negative subscale score (N) were -0.1 ± 0.7 (95%CI = -0.3-0.05) and -0.1 ± 0.5 (95%CI = -0.2-0.04) in vitamin D and control group respectively (p = 0.7) and there was a negative but not significant correlation between serum vitamin D level changes and PANSS negative subscale score (r = -0.04, p = 0.7). We did not find a relationship between serum vitamin D level changes and the improvement of negative and positive symptoms in schizophrenic patients and more randomized clinical trials are required to confirm our findings.

  11. Gatifloxacin versus ceftriaxone for uncomplicated enteric fever in Nepal: an open-label, two-centre, randomised controlled trial.

    Science.gov (United States)

    Arjyal, Amit; Basnyat, Buddha; Nhan, Ho Thi; Koirala, Samir; Giri, Abhishek; Joshi, Niva; Shakya, Mila; Pathak, Kamal Raj; Mahat, Saruna Pathak; Prajapati, Shanti Pradhan; Adhikari, Nabin; Thapa, Rajkumar; Merson, Laura; Gajurel, Damodar; Lamsal, Kamal; Lamsal, Dinesh; Yadav, Bharat Kumar; Shah, Ganesh; Shrestha, Poojan; Dongol, Sabina; Karkey, Abhilasha; Thompson, Corinne N; Thieu, Nga Tran Vu; Thanh, Duy Pham; Baker, Stephen; Thwaites, Guy E; Wolbers, Marcel; Dolecek, Christiane

    2016-05-01

    Because treatment with third-generation cephalosporins is associated with slow clinical improvement and high relapse burden for enteric fever, whereas the fluoroquinolone gatifloxacin is associated with rapid fever clearance and low relapse burden, we postulated that gatifloxacin would be superior to the cephalosporin ceftriaxone in treating enteric fever. We did an open-label, randomised, controlled, superiority trial at two hospitals in the Kathmandu valley, Nepal. Eligible participants were children (aged 2-13 years) and adult (aged 14-45 years) with criteria for suspected enteric fever (body temperature ≥38·0°C for ≥4 days without a focus of infection). We randomly assigned eligible patients (1:1) without stratification to 7 days of either oral gatifloxacin (10 mg/kg per day) or intravenous ceftriaxone (60 mg/kg up to 2 g per day for patients aged 2-13 years, or 2 g per day for patients aged ≥14 years). The randomisation list was computer-generated using blocks of four and six. The primary outcome was a composite of treatment failure, defined as the occurrence of at least one of the following: fever clearance time of more than 7 days after treatment initiation; the need for rescue treatment on day 8; microbiological failure (ie, blood cultures positive for Salmonella enterica serotype Typhi, or Paratyphi A, B, or C) on day 8; or relapse or disease-related complications within 28 days of treatment initiation. We did the analyses in the modified intention-to-treat population, and subpopulations with either confirmed blood-culture positivity, or blood-culture negativity. The trial was powered to detect an increase of 20% in the risk of failure. This trial was registered at ClinicalTrials.gov, number NCT01421693, and is now closed. Between Sept 18, 2011, and July 14, 2014, we screened 725 patients for eligibility. On July 14, 2014, the trial was stopped early by the data safety and monitoring board because S Typhi strains with high-level resistance to

  12. Relapse prevention in pediatric patients with ADHD treated with atomoxetine: a randomized, double-blind, placebo-controlled study.

    NARCIS (Netherlands)

    Michelson, D.; Danckaerts, M.; Gillberg, C.; Spencer, T.J.; Zuddas, A.; Faries, D.E.; Zhang, S.; Biederman, J.

    2004-01-01

    OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) is typically treated over extended periods; however, few placebo-controlled, long-term studies of efficacy have been reported. METHOD: In a global multicenter study, children and adolescents who responded to an initial 12-week, open-label

  13. 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

  14. 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

  15. Random fiber lasers based on artificially controlled backscattering fibers

    Science.gov (United States)

    Chen, Daru; Wang, Xiaoliang; She, Lijuan; Qiang, Zexuan; Yu, Zhangwei

    2017-10-01

    The random fiber laser (RFL) which is a milestone in laser physics and nonlinear optics, has attracted considerable attention recently. Most previous RFLs are based on distributed feedback of Rayleigh scattering amplified through stimulated Raman/Brillouin scattering effect in single mode fibers, which required long-distance (tens of kilometers) single mode fibers and high threshold up to watt-level due to the extremely small Rayleigh scattering coefficient of the fiber. We proposed and demonstrated a half-open cavity RFL based on a segment of a artificially controlled backscattering SMF(ACB-SMF) with a length of 210m, 310m or 390m. A fiber Bragg grating with the central wavelength of 1530nm and a segment of ACB-SMF forms the half-open cavity. The proposed RFL achieves the threshold of 25mW, 30mW and 30mW, respectively. Random lasing at the wavelength of 1530nm and the extinction ratio of 50dB is achieved when a segment of 5m EDF is pumped by a 980nm LD in the RFL. Another half-open cavity RFL based on a segment of a artificially controlled backscattering EDF(ACBS-EDF) is also demonstrated without an ACB-SMF. The 3m ACB-EDF is fabricated by using the femtosecond laser with pulse energy of 0.34mJ which introduces about 50 reflectors in the EDF. Random lasing at the wavelength of 1530nm is achieved with the output power of 7.5mW and the efficiency of 1.88%. Two novel RFLs with much short cavities have been achieved with low threshold and high efficiency.

  16. 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

  17. Morbidity and Mortality of Laparoscopic Versus Open D2 Distal Gastrectomy for Advanced Gastric Cancer: A Randomized Controlled Trial.

    Science.gov (United States)

    Hu, Yanfeng; Huang, Changming; Sun, Yihong; Su, Xiangqian; Cao, Hui; Hu, Jiankun; Xue, Yingwei; Suo, Jian; Tao, Kaixiong; He, Xianli; Wei, Hongbo; Ying, Mingang; Hu, Weiguo; Du, Xiaohui; Chen, Pingyan; Liu, Hao; Zheng, Chaohui; Liu, Fenglin; Yu, Jiang; Li, Ziyu; Zhao, Gang; Chen, Xinzu; Wang, Kuan; Li, Ping; Xing, Jiadi; Li, Guoxin

    2016-04-20

    The safety and efficacy of radical laparoscopic distal gastrectomy (LG) with D2 lymphadenectomy for the treatment of advanced gastric cancer (AGC) remain controversial. We conducted a randomized controlled trial to compare laparoscopic and conventional open distal gastrectomy with D2 lymph node dissections for AGC. Between September 2012 and December 2014, 1,056 patients with clinical stage T2-4aN0-3M0 gastric cancer were eligible for inclusion. They were randomly assigned to either the LG with D2 lymphadenectomy group (n = 528) or the open gastrectomy (OG) with D2 lymphadenectomy group (n = 528). Fifteen experienced surgeons from 14 institutions in China participated in the study. The morbidity and mortality within 30 days after surgery between the LG (n = 519) and the OG (n = 520) groups were compared on the basis of the modified intention-to-treat principle. Postoperative complications were stratified according to the Clavien-Dindo classification. The compliance rates of D2 lymphadenectomy were similar between the LG and OG groups (99.4% v 99.6%; P = .845). The postoperative morbidity was 15.2% in the LG group and 12.9% in OG group with no significant difference (difference, 2.3%; 95% CI, -1.9 to 6.6; P = .285). The mortality rate was 0.4% for the LG group and zero for the OG group (difference, 0.4%; 95% CI, -0.4 to 1.4; P = .249). The distribution of severity was similar between the two groups (P = .314). Experienced surgeons can safely perform LG with D2 lymphadenectomy for AGC. © 2016 by American Society of Clinical Oncology.

  18. 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.

  19. A randomized double-blind, placebo-controlled efficacy and safety study of ALO-02 (extended-release oxycodone surrounding sequestered naltrexone) for moderate-to-severe chronic low back pain treatment.

    Science.gov (United States)

    Rauck, Richard L; Hale, Martin E; Bass, Almasa; Bramson, Candace; Pixton, Glenn; Wilson, Jacquelyn G; Setnik, Beatrice; Meisner, Paul; Sommerville, Kenneth W; Malhotra, Bimal K; Wolfram, Gernot

    2015-09-01

    The objective of this multicenter, double-blind, placebo-controlled, randomized withdrawal study was to evaluate the efficacy and safety of ALO-02, an abuse-deterrent formulation containing pellets of extended-release oxycodone hydrochloride (HCl) surrounding sequestered naltrexone HCl, compared with placebo in the treatment of moderate-to-severe chronic low back pain. An open-label titration period in which all patients received ALO-02 was followed by a double-blind treatment period where patients meeting treatment response criteria were randomized to either a fixed dose of ALO-02 or placebo. Daily average low back pain was assessed using an 11-point numeric rating scale (NRS)-Pain. Of the 663 patients screened, 410 received ALO-02 during the open-label conversion and titration period and 281 patients were randomized to the double-blind treatment period (n = 134, placebo; n = 147, ALO-02). Change in the mean NRS-Pain score from randomization baseline to the final 2 weeks of the treatment period was significantly different favoring ALO-02 compared with placebo (P = 0.0114). Forty-four percent of patients treated with placebo and 57.5% of patients treated with ALO-02 reported ≥30% improvement in weekly average NRS-Pain scores from screening to the final 2 weeks of the treatment period (P = 0.0248). In the double-blind treatment period, 56.8% of patients in the ALO-02 group and 56.0% of patients in the placebo group experienced a treatment-emergent adverse event (TEAE). The most common treatment-related TEAEs for ALO-02 during the treatment period were nausea, vomiting, and constipation, consistent with opioid therapy. ALO-02 has been demonstrated to provide significant reduction of pain in patients with chronic low back pain and has a safety profile similar to other opioids.

  20. Open release versus radiofrequency microtenotomy in the treatment of lateral epicondylitis: a prospective randomized controlled trial.

    Science.gov (United States)

    Hamlin, Katharine; Munro, Christopher; Barker, Scott L; McKenna, Sean; Kumar, Kapil

    2018-01-01

    Optimal surgical treatment of lateral epicondylitis remains uncertain. Recently, radiofrequency microtenotomy (RFMT) has been proposed as a suitable treatment. We compared RFMT with standard open release (OR) in this prospective randomized controlled trial. In total, 41 patients with symptoms for at least 6 months were randomized into two groups: 23 patients had RFMT and 18 had OR. Two patients from RFMT withdrew. Each patient underwent Numerical Rating Scale (NRS) pain score, grip strength and Disabilities of the Arm, Shoulder and Hand (DASH) scores pre-operatively and at 6 weeks. Pain and DASH scores were repeated at 6 months and 12 months. NRS pain scores improved by 4.8 points for RFMT and by 3.9 points for OR. There was a significant improvement in both groups from pre-operative scores, although there was no statistically significant difference between the groups at 1 year. Grip strength improved by 31% in the RFMT group compared to 38% in OR. There was no significant difference between the initial and 6 weeks scores or between treatments. At 1 year, DASH was 39.8 points for RFMT and 24.4 points for OR. There was a significant improvement in both groups from pre-operative scores, although there was no statistically significant difference between the groups at 1 year. Both groups showed significant improvements and similar benefit to the patient. The results of the present study do not show any benefit of RFMT over the standard OR. As a result of the extra expense of RFMT, we therefore recommend that OR is offered as the standard surgical management.

  1. Ior-CEA-1: Labelling, quality control and clinical evaluation

    International Nuclear Information System (INIS)

    Pimentel, G.J.

    1998-01-01

    Within the Co-ordinated Programme on Labelling, Quality Control and Evaluation of Monoclonal Antibodies, the IAEA has made a great effort to expand efficient labelling methods, mainly those with radioisotopes which have been used for radioimmunoscintigraphy. In this sense, more recently 99 Tc m has been mostly employed in the majority of the investigations due to its ideal physical characteristics. Efficient labelling of monoclonal antibodies depends on a number of factors including the method and way of the label incorporation into the protein. During the last years several direct labelling approaches have been developed, which led to attain simple and inexpensive methods for medical practice, as well as safe and stable techniques which bring accurate and good quality images. Accordingly, this paper describes the results obtained during last five years which come from the comparison among different labelling systems, passing through the quality control to test the labelled monoclonal stability and the protein bioreactivity, to continue in the clinical evaluation of ior-CEA-1, as well as the evaluation of other antibodies. Up to now we have evaluated more than 70 patients with the anti-CEA monoclonal antibody (ior-CEA-1), examined in different clinical assays such as: pilot, phase I-II and extensive phase III-IV trials, whose results are encouraging. It confirms that the employed labelling approach was safe and adequate

  2. Open- and Closed-Skill Exercise Interventions Produce Different Neurocognitive Effects on Executive Functions in the Elderly: A 6-Month Randomized, Controlled Trial

    Directory of Open Access Journals (Sweden)

    Chia-Liang Tsai

    2017-09-01

    Full Text Available This study aimed to explore the effects of open- and closed-skill exercise interventions on the neurocognitive performance of executive functions in the elderly. Sixty-four healthy elderly males were randomly assigned to either a closed-skill (bike riding or brisk walking/jogging, n = 22, open-skill (table tennis, n = 21, or control (n = 21 group. Various neuropsychological [e.g., accuracy rates (AR and reaction time (RT] and electrophysiological [e.g., event-related potential (ERP P3 component] measures were assessed during a variant of the task-switching paradigm, as well as an N-back task at baseline and after either a 6-month exercise intervention or control period. The results showed that, when performing the task-switching paradigm, the two exercise groups relative to control group showed significantly faster RTs in the switch trials after the exercise intervention. However, the RT facilitation in the non-switch and switch trials post-exercise relative to pre-exercise only emerged in the open-skill group. In terms of the N-back task, the two exercise groups significantly increased ARs in the 1-back condition after the exercise intervention, and the beneficial AR effect on the 2-back condition only emerged in the closed-skill group. In addition, the two exercise groups exhibited significantly larger P3 amplitudes on the frontal-to-parietal cortex areas after the exercise intervention relative to the baseline when performing the two cognitive tasks. These neurocognitive results still remained unchanged even when the confounding factors (e.g., cardiorespiratory fitness, social participation, and BMI were controlled for. The present study concluded that, although 6-month open- and closed-skill exercise interventions facilitate overall electrophysiological effects (i.e., increased ERP P3 amplitudes on the frontal-to-parietal cortices in the elderly, the two exercise modes produced different levels of neuropsychologically beneficial effects on

  3. 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

  4. 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

  5. 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.

  6. Randomized Controlled Trials to Define Viral Load Thresholds for Cytomegalovirus Pre-Emptive Therapy.

    Directory of Open Access Journals (Sweden)

    Paul D Griffiths

    Full Text Available To help decide when to start and when to stop pre-emptive therapy for cytomegalovirus infection, we conducted two open-label randomized controlled trials in renal, liver and bone marrow transplant recipients in a single centre where pre-emptive therapy is indicated if viraemia exceeds 3000 genomes/ml (2520 IU/ml of whole blood.Patients with two consecutive viraemia episodes each below 3000 genomes/ml were randomized to continue monitoring or to immediate treatment (Part A. A separate group of patients with viral load greater than 3000 genomes/ml was randomized to stop pre-emptive therapy when two consecutive levels less than 200 genomes/ml (168 IU/ml or less than 3000 genomes/ml were obtained (Part B. For both parts, the primary endpoint was the occurrence of a separate episode of viraemia requiring treatment because it was greater than 3000 genomes/ml.In Part A, the primary endpoint was not significantly different between the two arms; 18/32 (56% in the monitor arm had viraemia greater than 3000 genomes/ml compared to 10/27 (37% in the immediate treatment arm (p = 0.193. However, the time to developing an episode of viraemia greater than 3000 genomes/ml was significantly delayed among those randomized to immediate treatment (p = 0.022. In Part B, the primary endpoint was not significantly different between the two arms; 19/55 (35% in the less than 200 genomes/ml arm subsequently had viraemia greater than 3000 genomes/ml compared to 23/51 (45% among those randomized to stop treatment in the less than 3000 genomes/ml arm (p = 0.322. However, the duration of antiviral treatment was significantly shorter (p = 0.0012 in those randomized to stop treatment when viraemia was less than 3000 genomes/ml.The results illustrate that patients have continuing risks for CMV infection with limited time available for intervention. We see no need to alter current rules for stopping or starting pre-emptive therapy.

  7. Anaesthesiological strategies in elective craniotomy: randomized, equivalence, open trial--the NeuroMorfeo trial.

    Science.gov (United States)

    Citerio, Giuseppe; Franzosi, Maria Grazia; Latini, Roberto; Masson, Serge; Barlera, Simona; Guzzetti, Stefano; Pesenti, Antonio

    2009-04-06

    Many studies have attempted to determine the "best" anaesthetic technique for neurosurgical procedures in patients without intracranial hypertension. So far, no study comparing intravenous (IA) with volatile-based neuroanaesthesia (VA) has been able to demonstrate major outcome differences nor a superiority of one of the two strategies in patients undergoing elective supratentorial neurosurgery. Therefore, current practice varies and includes the use of either volatile or intravenous anaesthetics in addition to narcotics. Actually the choice of the anaesthesiological strategy depends only on the anaesthetists' preferences or institutional policies. This trial, named NeuroMorfeo, aims to assess the equivalence between volatile and intravenous anaesthetics for neurosurgical procedures. NeuroMorfeo is a multicenter, randomized, open label, controlled trial, based on an equivalence design. Patients aged between 18 and 75 years, scheduled for elective craniotomy for supratentorial lesion without signs of intracranial hypertension, in good physical state (ASA I-III) and Glasgow Coma Scale (GCS) equal to 15, are randomly assigned to one of three anaesthesiological strategies (two VA arms, sevoflurane + fentanyl or sevoflurane + remifentanil, and one IA, propofol + remifentanil). The equivalence between intravenous and volatile-based neuroanaesthesia will be evaluated by comparing the intervals required to reach, after anaesthesia discontinuation, a modified Aldrete score > or = 9 (primary end-point). Two statistical comparisons have been planned: 1) sevoflurane + fentanyl vs. propofol + remifentanil; 2) sevoflurane + remifentanil vs. propofol + remifentanil. Secondary end-points include: an assessment of neurovegetative stress based on (a) measurement of urinary catecholamines and plasma and urinary cortisol and (b) estimate of sympathetic/parasympathetic balance by power spectrum analyses of electrocardiographic tracings recorded during anaesthesia; intraoperative

  8. 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.

  9. Effects of adjunctive treatment with aripiprazole on body weight and clinical efficacy in schizophrenia patients treated with clozapine: a randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Fleischhacker, W Wolfgang; Heikkinen, Martti E; Olié, Jean-Pierre; Landsberg, Wally; Dewaele, Patricia; McQuade, Robert D; Loze, Jean-Yves; Hennicken, Delphine; Kerselaers, Wendy

    2010-09-01

    Clozapine is associated with significant weight gain and metabolic disturbances. This multicentre, randomized study comprised a double-blind, placebo-controlled treatment phase of 16 wk, and an open-label extension phase of 12 wk. Outpatients who met DSM-IV-TR criteria for schizophrenia, who were not optimally controlled while on stable dosage of clozapine for > or =3 months and had experienced weight gain of > or =2.5 kg while taking clozapine, were randomized (n=207) to aripiprazole at 5-15 mg/d or placebo, in addition to a stable dose of clozapine. The primary endpoint was mean change from baseline in body weight at week 16 (last observation carried forward). Secondary endpoints included clinical efficacy, body mass index (BMI) and waist circumference. A statistically significant difference in weight loss was reported for aripiprazole vs. placebo (-2.53 kg vs. -0.38 kg, respectively, difference=-2.15 kg, pweight, BMI and fasting cholesterol benefits to patients suboptimally treated with clozapine. Improvements may reduce metabolic risk factors associated with clozapine treatment.

  10. Antibiotic treatment for 6 weeks versus 12 weeks in patients with pyogenic vertebral osteomyelitis: an open-label, non-inferiority, randomised, controlled trial.

    Science.gov (United States)

    Bernard, Louis; Dinh, Aurélien; Ghout, Idir; Simo, David; Zeller, Valerie; Issartel, Bertrand; Le Moing, Vincent; Belmatoug, Nadia; Lesprit, Philippe; Bru, Jean-Pierre; Therby, Audrey; Bouhour, Damien; Dénes, Eric; Debard, Alexa; Chirouze, Catherine; Fèvre, Karine; Dupon, Michel; Aegerter, Philippe; Mulleman, Denis

    2015-03-07

    Duration of treatment for patients with vertebral osteomyelitis is mainly based on expert recommendation rather than evidence. We aimed to establish whether 6 weeks of antibiotic treatment is non-inferior to 12 weeks in patients with pyogenic vertebral osteomyelitis. In this open-label, non-inferiority, randomised controlled trial, we enrolled patients aged 18 years or older with microbiologically confirmed pyogenic vertebral osteomyelitis and typical radiological features from 71 medical care centres across France. Patients were randomly assigned to either 6 weeks or 12 weeks of antibiotic treatment (physician's choice in accordance with French guidelines) by a computer-generated randomisation list of permuted blocks, stratified by centre. The primary endpoint was the proportion of patients who were classified as cured at 1 year by a masked independent validation committee, analysed by intention to treat. Non-inferiority would be declared if the proportion of cured patients assigned to 6 weeks of treatment was not less than the proportion of cured patients assigned to 12 weeks of treatment, within statistical variability, by an absolute margin of 10%. This trial is registered with EudraCT, number 2006-000951-18, and Clinical Trials.gov, number NCT00764114. Between Nov 15, 2006, and March 15, 2011, 359 patients were randomly assigned, of whom six in the 6-week group and two in the 12-week group were excluded after randomisation. 176 patients assigned to the 6-week treatment regimen and 175 to the 12-week treatment regimen were analysed by intention to treat. 160 (90·9%) of 176 patients in the 6-week group and 159 (90·9%) of 175 of those in the 12-week group met the criteria for clinical cure. The difference between the groups (0·05%, 95% CI -6·2 to 6·3) showed the non-inferiority of the 6-week regimen when compared with the 12-week regimen. 50 patients in the 6-week group and 51 in the 12-week group had adverse events, the most common being death (14 [8%] in

  11. Effect of comorbid tics on a clinically meaningful response to 8-week open-label trial of fluoxetine in obsessive compulsive disorder.

    Science.gov (United States)

    Husted, David S; Shapira, Nathan A; Murphy, Tanya K; Mann, Giselle D; Ward, Herbert E; Goodman, Wayne K

    2007-01-01

    Currently, there are limited published data evaluating the effects of tics on serotonin reuptake inhibitor (SRI) monotherapy responses in treating obsessive-compulsive disorder (OCD). One retrospective case-controlled analysis of OCD patients treated with SRI monotherapy showed lesser improvement in OCD symptoms in patients with tics than those without. However, more recently there were preliminary reports of OCD subjects treated with SRI monotherapy which did not demonstrate poorer response in subjects with tics or Tourette's Syndrome (TS). The specific aim of this study was to investigate whether the presence of comorbid chronic tics affected "clinically meaningful improvement" [McDougle, C.J., Goodman, W.K., Leckman, J.F., Barr, L.C., Heninger, G.R., Price, L.H., 1993. The efficacy of fluvoxamine in obsessive-compulsive disorder: effects of comorbid chronic tic disorder. Journal of Clinical Psychopharmacology 13, 354-358] of OCD in an 8-week open-label trial of fluoxetine monotherapy. Seventy-four adult subjects (13 patients with comorbid chronic tics and 61 patients without tics) with a primary DSM-IV OCD diagnosis were treated with up to 40mg fluoxetine for 8 weeks and had at least one post-baseline evaluation. The results indicate that there was a significant response by time in both fluoxetine-with-tic subjects and fluoxetine-without-tic subjects. Additionally, there were 3 (23.0%) OCD subjects with tics who had clinically meaningful improvement versus 16 (26.2%) OCD subjects without tics that demonstrated similar levels of improvement. These findings indicate that OCD patients with or without chronic tic disorders did not have a differential response to an 8-week open-label trial of fluoxetine. Limitations include the relatively low number of tic subjects and the open-label nature of the study. Additional data are needed on how comorbid tics may affect SRI treatment response in OCD.

  12. 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

  13. 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.

  14. 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.

  15. A randomized controlled trial of levosimendan to reduce mortality in high-risk cardiac surgery patients (CHEETAH): Rationale and design.

    Science.gov (United States)

    Zangrillo, Alberto; Alvaro, Gabriele; Pisano, Antonio; Guarracino, Fabio; Lobreglio, Rosetta; Bradic, Nikola; Lembo, Rosalba; Gianni, Stefano; Calabrò, Maria Grazia; Likhvantsev, Valery; Grigoryev, Evgeny; Buscaglia, Giuseppe; Pala, Giovanni; Auci, Elisabetta; Amantea, Bruno; Monaco, Fabrizio; De Vuono, Giovanni; Corcione, Antonio; Galdieri, Nicola; Cariello, Claudia; Bove, Tiziana; Fominskiy, Evgeny; Auriemma, Stefano; Baiocchi, Massimo; Bianchi, Alessandro; Frontini, Mario; Paternoster, Gianluca; Sangalli, Fabio; Wang, Chew-Yin; Zucchetti, Maria Chiara; Biondi-Zoccai, Giuseppe; Gemma, Marco; Lipinski, Michael J; Lomivorotov, Vladimir V; Landoni, Giovanni

    2016-07-01

    Patients undergoing cardiac surgery are at risk of perioperative low cardiac output syndrome due to postoperative myocardial dysfunction. Myocardial dysfunction in patients undergoing cardiac surgery is a potential indication for the use of levosimendan, a calcium sensitizer with 3 beneficial cardiovascular effects (inotropic, vasodilatory, and anti-inflammatory), which appears effective in improving clinically relevant outcomes. Double-blind, placebo-controlled, multicenter randomized trial. Tertiary care hospitals. Cardiac surgery patients (n = 1,000) with postoperative myocardial dysfunction (defined as patients with intraaortic balloon pump and/or high-dose standard inotropic support) will be randomized to receive a continuous infusion of either levosimendan (0.05-0.2 μg/[kg min]) or placebo for 24-48 hours. The primary end point will be 30-day mortality. Secondary end points will be mortality at 1 year, time on mechanical ventilation, acute kidney injury, decision to stop the study drug due to adverse events or to start open-label levosimendan, and length of intensive care unit and hospital stay. We will test the hypothesis that levosimendan reduces 30-day mortality in cardiac surgery patients with postoperative myocardial dysfunction. This trial is planned to determine whether levosimendan could improve survival in patients with postoperative low cardiac output syndrome. The results of this double-blind, placebo-controlled randomized trial may provide important insights into the management of low cardiac output in cardiac surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. An open, randomized, parallel-group study to compare the efficacy and safety profile of inhaled human insulin (exubera) with meformin as adjunctive therapy in patients with type 2 diabetes poorly controlled on a sulfonylurea: response to mikhail and cope

    DEFF Research Database (Denmark)

    Barnett, Anthony H.; Dreyer, Manfred; Lange, Peter

    2006-01-01

    OBJECTIVE: To compare the efficacy and safety profile of adding inhaled human insulin (INH; Exubera) or metformin to sulfonylurea monotherapy in patients with poorly controlled type 2 diabetes. RESEARCH DESIGN AND METHODS: We performed an open-label, parallel, 24-week, multicenter trial. At week -1......: In patients with type 2 diabetes poorly controlled on a sulfonylurea (A1C >9.5%), the addition of premeal INH significantly improves glycemic control compared with adjunctive metformin and is well tolerated....

  17. Milligan-Morgan (Open) Versus Ferguson Haemorrhoidectomy (Closed): A Systematic Review and Meta-Analysis of Published Randomized, Controlled Trials.

    Science.gov (United States)

    Bhatti, Muhammad I; Sajid, Muhammad Shafique; Baig, Mirza K

    2016-06-01

    The purpose of this article is to systematically analyse the randomized, controlled trials (RCTs) comparing Ferguson or closed haemorrhoidectomy (CH) versus open haemorrhoidectomy (OH) or Milligan-Morgan haemorrhoidectomy in the management of haemorrhoidal disease (HD). RCTs on the effectiveness of CH and OH in the management of HD were analysed systematically using RevMan(®), and combined outcome was expressed as odds ratio (OR) and standardized mean difference. Eleven CRTs encompassing 1326 patients were analysed systematically. There was significant heterogeneity among included trials. Therefore, in the random effects model, CH was associated with a reduced post-operative pain (SMD, -0.36; 95 % CI, -0.64, -0.07; z = 2.45; p = 0.01), faster wound healing (OR, 0.08; 95 % CI, 0.02, 0.24; z = 4.33; p SMD, 6.10; 95 % CI, 3.21, 8.98; z = 4.13; p SMD, -0.33; 95 % CI, -0.68, 0.03; z = 1.82; p = 0.07), length of hospital stay, post-operative complications, HD recurrence and risk of surgical site infection were similar in both groups. CH has clinically measurable advantages over OH in terms of reduced post-operative pain, lower risk of post-operative bleeding and faster wound healing.

  18. Labelling and quality control of 99mTc labelled somatostatin analogues

    International Nuclear Information System (INIS)

    Poramatikul, N.; Sangsuriyan, J.; Kongpeth, P.; Ngamprayad, T.; Laloknam, S.; Permtermsin, C.; Madsomboon, N.

    2001-01-01

    To standardize interlaboratory reproducibility, iodination of RC-160 with 125 I and direct labelling of RC-160 with 99m Tc, quality control and binding assay were performed. Two conjugated peptides, HYNIC-RC-160 and MAG-3-RC-160, were synthesized. The conjugated peptides were radiolabelled with 99m Tc via co-ligands; 99m Tc-MAG-3-RC-160 via glucoheptonate, 99m Tc-HYNIC-RC-160 via EDDA and tricine. Conditions for labelling were optimized. Analytical and purification methods for the labelled products were developed. Radiochemical purity test of 99m Tc labelled peptides was performed by HPLC with gradient elution of 0.1%TFA/water and acetonitrile, or by ITLC-SG in saline and in 50% acetonitrile. The contaminants in 99m Tc radiolabelled product were separated by elution from SEPPAK C-18 cartridge by 0.1% acetic acid and the pure product was eluted out of SEPPAK column by 50% acetonitrile with about 68% recovery. Stability of the purified 99m Tc-MAG3-RC-160 stored at -20 deg. C was more than 72 h. 99m Tc-MAG-3-RC-160 showed a high equilibrium dissociation constant with K D of 26 pmole/mg protein and B max of 7.9 mM. (author)

  19. Robotic-assisted versus open radical cystectomy in bladder cancer: A meta-analysis of four randomized controlled trails.

    Science.gov (United States)

    Tang, Jin-Qiu; Zhao, Zhihong; Liang, Yiwen; Liao, Guixiang

    2018-02-01

    Robot-assisted radical cystectomy (RARC) is increasing annually for treatment of bladder cancer. The objective of this meta-analysis was to compare the safety and efficacy of RARC and open radical cystectomy (ORC) for bladder cancer. Our meta-analysis searches were conducted using PubMed, Web of Science, and Cochrane Library databases to identify randomized controlled trials (RCT) assessing the two techniques. Four RCT studies were identified, including 239 cases. Our studies indicated that RARC was associated with longer operative time (WMD: 69.69, 95% CI:17.25 to122.12; P= 0.009), lower estimated blood loss (WMD: -299.83, 95% CI:-414.66to -184.99; P<0.00001). The two groups had no significant difference in overall perioperative complications, length of hospital stay, lymph node yield and positive surgical margins. RARC is mini-invasive alternative to ORC for bladder cancer. The advantage of RARC was reduced estimated blood loss. More studies are needed to compare the two techniques. Copyright © 2017 John Wiley & Sons, Ltd.

  20. Intensive speech and language therapy in patients with chronic aphasia after stroke: a randomised, open-label, blinded-endpoint, controlled trial in a health-care setting.

    Science.gov (United States)

    Breitenstein, Caterina; Grewe, Tanja; Flöel, Agnes; Ziegler, Wolfram; Springer, Luise; Martus, Peter; Huber, Walter; Willmes, Klaus; Ringelstein, E Bernd; Haeusler, Karl Georg; Abel, Stefanie; Glindemann, Ralf; Domahs, Frank; Regenbrecht, Frank; Schlenck, Klaus-Jürgen; Thomas, Marion; Obrig, Hellmuth; de Langen, Ernst; Rocker, Roman; Wigbers, Franziska; Rühmkorf, Christina; Hempen, Indra; List, Jonathan; Baumgaertner, Annette

    2017-04-15

    Treatment guidelines for aphasia recommend intensive speech and language therapy for chronic (≥6 months) aphasia after stroke, but large-scale, class 1 randomised controlled trials on treatment effectiveness are scarce. We aimed to examine whether 3 weeks of intensive speech and language therapy under routine clinical conditions improved verbal communication in daily-life situations in people with chronic aphasia after stroke. In this multicentre, parallel group, superiority, open-label, blinded-endpoint, randomised controlled trial, patients aged 70 years or younger with aphasia after stroke lasting for 6 months or more were recruited from 19 inpatient or outpatient rehabilitation centres in Germany. An external biostatistician used a computer-generated permuted block randomisation method, stratified by treatment centre, to randomly assign participants to either 3 weeks or more of intensive speech and language therapy (≥10 h per week) or 3 weeks deferral of intensive speech and language therapy. The primary endpoint was between-group difference in the change in verbal communication effectiveness in everyday life scenarios (Amsterdam-Nijmegen Everyday Language Test A-scale) from baseline to immediately after 3 weeks of treatment or treatment deferral. All analyses were done using the modified intention-to-treat population (those who received 1 day or more of intensive treatment or treatment deferral). This study is registered with ClinicalTrials.gov, number NCT01540383. We randomly assigned 158 patients between April 1, 2012, and May 31, 2014. The modified intention-to-treat population comprised 156 patients (78 per group). Verbal communication was significantly improved from baseline to after intensive speech and language treatment (mean difference 2·61 points [SD 4·94]; 95% CI 1·49 to 3·72), but not from baseline to after treatment deferral (-0·03 points [4·04]; -0·94 to 0·88; between-group difference Cohen's d 0·58; p=0·0004). Eight patients had

  1. Safety and efficacy of diaphragm pacing in patients with respiratory insufficiency due to amyotrophic lateral sclerosis (DiPALS): a multicentre, open-label, randomised controlled trial.

    Science.gov (United States)

    2015-09-01

    Non-invasive ventilation is part of the standard of care for treatment of respiratory failure in patients with amyotrophic lateral sclerosis (ALS). The NeuRx RA/4 Diaphragm Pacing System has received Humanitarian Device Exemption approval from the US Food and Drug Administration for treatment of respiratory failure in patients with ALS. We aimed to establish the safety and efficacy of diaphragm pacing with this system in patients with respiratory muscle weakness due to ALS. We undertook a multicentre, open-label, randomised controlled trial at seven specialist ALS and respiratory centres in the UK. Eligible participants were aged 18 years or older with laboratory supported probable, clinically probable, or clinically definite ALS; stable riluzole treatment for at least 30 days; and respiratory insufficiency. We randomly assigned participants (1:1), via a centralised web-based randomisation system with minimisation that balanced patients for age, sex, forced vital capacity, and bulbar function, to receive either non-invasive ventilation plus pacing with the NeuRx RA/4 Diaphragm Pacing System or non-invasive ventilation alone. Patients, carers, and outcome assessors were not masked to treatment allocation. The primary outcome was overall survival, defined as the time from randomisation to death from any cause. Analysis was by intention to treat. This trial is registered, ISRCTN number 53817913. Between Dec 5, 2011, and Dec 18, 2013, we randomly assigned 74 participants to receive either non-invasive ventilation alone (n=37) or non-invasive ventilation plus diaphragm pacing (n=37). On Dec 18, 2013, the Data Monitoring and Ethics Committee (DMEC) recommended suspension of recruitment on the basis of overall survival figures. Randomly assigned participants continued as per the study protocol until June 23, 2014, when the DMEC advised discontinuation of pacing in all patients. Follow-up assessments continued until the planned end of the study in December, 2014. Survival

  2. 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

  3. Physical performance in recently aged adults after 6 weeks traditional Thai dance: a randomized controlled trial

    Science.gov (United States)

    Janyacharoen, Taweesak; Laophosri, Maneepun; Kanpittaya, Jaturat; Auvichayapat, Paradee; Sawanyawisuth, Kittisak

    2013-01-01

    Background Exercise has been shown to be effective in cardiovascular endurance in the elderly. We studied the effect of Thai dancing on physical performance of Thai elderly. Methods This was an open-labeled, randomized intervention study. The Thai dancing group exercised for 40 minutes three times a week for 6 weeks. Physical performance ability was the primary outcome, including a 6-minute walk test (6MWT), five-times sit-to-stand (FTSST), and a sit-and-reach test measured before and after 6 weeks of intervention. Results There were 42 subjects enrolled in the study, and 38 female subjects completed (20 in Thai dance group, 18 controls), with an average age of 65.8 ± 5.1 years. The Thai dance group had significantly better physical performance in all measurements at the end of the study. The 6MWT was longer (416.7 ± 58.7 versus 345.7 ± 55.1 m; P = 0.011), FTSST was quicker (10.2 ± 1.5 versus 14.4 ± 3.3 seconds; P dance group than the control group. Conclusion Thai dance can improve physical performance in recently aged (elderly) female adults. PMID:23950640

  4. Differential quantitative proteomics of Porphyromonas gingivalis by linear ion trap mass spectrometry: Non-label methods comparison, q-values and LOWESS curve fitting

    Science.gov (United States)

    Xia, Qiangwei; Wang, Tiansong; Park, Yoonsuk; Lamont, Richard J.; Hackett, Murray

    2007-01-01

    Differential analysis of whole cell proteomes by mass spectrometry has largely been applied using various forms of stable isotope labeling. While metabolic stable isotope labeling has been the method of choice, it is often not possible to apply such an approach. Four different label free ways of calculating expression ratios in a classic "two-state" experiment are compared: signal intensity at the peptide level, signal intensity at the protein level, spectral counting at the peptide level, and spectral counting at the protein level. The quantitative data were mined from a dataset of 1245 qualitatively identified proteins, about 56% of the protein encoding open reading frames from Porphyromonas gingivalis, a Gram-negative intracellular pathogen being studied under extracellular and intracellular conditions. Two different control populations were compared against P. gingivalis internalized within a model human target cell line. The q-value statistic, a measure of false discovery rate previously applied to transcription microarrays, was applied to proteomics data. For spectral counting, the most logically consistent estimate of random error came from applying the locally weighted scatter plot smoothing procedure (LOWESS) to the most extreme ratios generated from a control technical replicate, thus setting upper and lower bounds for the region of experimentally observed random error.

  5. 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...

  6. Ziprasidone Augmentation of Escitalopram for Major Depressive Disorder: Cardiac, Endocrine, Metabolic, and Motoric Effects in a Randomized, Double-Blind, Placebo-Controlled Study.

    Science.gov (United States)

    Mischoulon, David; Shelton, Richard C; Baer, Lee; Bobo, William V; Curren, Laura; Fava, Maurizio; Papakostas, George I

    2017-04-01

    To examine motoric, cardiovascular, endocrine, and metabolic effects of adjunctive ziprasidone in adults with major depressive disorder (MDD) and prior nonresponse to 8 weeks of open-label escitalopram. A multicenter, parallel, randomized, double-blind, placebo-controlled trial was conducted at 3 US academic medical centers from July 2008 to October 2013. Recruited were 139 outpatients with persistent DSM-IV MDD following an 8-week open-label trial of escitalopram. Subjects were then randomized to adjunctive ziprasidone (escitalopram + ziprasidone, n = 71) or placebo (escitalopram + placebo, n = 68) for 8 additional weeks. Cardiac and metabolic measures were obtained at each treatment visit. Barnes Akathisia Scale and Abnormal Involuntary Movement Scale (AIMS) scores were also obtained. Changes in outcome measures for each treatment group were compared by independent-samples t test. A trend toward significance (P = .06) in corrected QT interval (QTc) increase was observed for ziprasidone (mean [SD] = 8.8 [20.2] milliseconds) versus placebo (-0.02 [25.5] milliseconds). Ziprasidone-treated patients had a significantly greater increase in global akathisia scores (P = .01) and significant weight increase (mean [SD] = 3.5 [11.8] kg, or 7.7 [26.1] lb) compared to placebo (1.0 [6.4] kg, or 2.2 [14.1] lb) (P = .03). No significant changes in AIMS scores were observed for either treatment group. Adjunctive ziprasidone, added to escitalopram, led to a greater weight gain and greater but modest akathisia compared to placebo. The effect of ziprasidone on QTc showed a trend toward significance, and therefore caution should be used in the administration of ziprasidone. While ziprasidone augmentation in patients with MDD appears safe, precautions should be taken in practice, specifically regular monitoring of electrocardiogram, weight, extrapyramidal symptoms, and involuntary movements. ClinicalTrials.gov identifier: NCT00633399​​. © Copyright 2016 Physicians Postgraduate

  7. Comparison of MAPIE versus MAP in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOS-1): an open-label, international, randomised controlled trial

    NARCIS (Netherlands)

    Marina, Neyssa M.; Smeland, Sigbjørn; Bielack, Stefan S.; Bernstein, Mark; Jovic, Gordana; Krailo, Mark D.; Hook, Jane M.; Arndt, Carola; van den Berg, Henk; Brennan, Bernadette; Brichard, Bénédicte; Brown, Ken L. B.; Butterfass-Bahloul, Trude; Calaminus, Gabriele; Daldrup-Link, Heike E.; Eriksson, Mikael; Gebhardt, Mark C.; Gelderblom, Hans; Gerss, Joachim; Goldsby, Robert; Goorin, Allen; Gorlick, Richard; Grier, Holcombe E.; Hale, Juliet P.; Hall, Kirsten Sundby; Hardes, Jendrik; Hawkins, Douglas S.; Helmke, Knut; Hogendoorn, Pancras C. W.; Isakoff, Michael S.; Janeway, Katherine A.; Jürgens, Heribert; Kager, Leo; Kühne, Thomas; Lau, Ching C.; Leavey, Patrick J.; Lessnick, Stephen L.; Mascarenhas, Leo; Meyers, Paul A.; Mottl, Hubert; Nathrath, Michaela; Papai, Zsuzsanna; Randall, R. Lor; Reichardt, Peter; Renard, Marleen; Safwat, Akmal Ahmed; Schwartz, Cindy L.; Stevens, Michael C. G.; Strauss, Sandra J.; Teot, Lisa; Werner, Mathias; Sydes, Matthew R.; Whelan, Jeremy S.

    2016-01-01

    We designed the EURAMOS-1 trial to investigate whether intensified postoperative chemotherapy for patients whose tumour showed a poor response to preoperative chemotherapy (≥10% viable tumour) improved event-free survival in patients with high-grade osteosarcoma. EURAMOS-1 was an open-label,

  8. The Effects of Individual Upper Alpha Neurofeedback in ADHD: An Open-Label Pilot Study

    OpenAIRE

    Escolano , Carlos; Navarro-Gil , Mayte; Garcia-Campayo , Javier; Congedo , Marco; Minguez , Javier

    2014-01-01

    International audience; Standardized neurofeedback (NF) protocols have been extensively evaluated in attention-deficit/hyperactivity disorder (ADHD). However, such protocols do not account for the large EEG heterogeneity in ADHD. Thus, individualized approaches have been suggested to improve the clinical outcome. In this direction, an open-label pilot study was designed to evaluate a NF protocol of relative upper alpha power enhancement in fronto-central sites. Upper alpha band was individual...

  9. Controllable Subspaces of Open Quantum Dynamical Systems

    International Nuclear Information System (INIS)

    Zhang Ming; Gong Erling; Xie Hongwei; Hu Dewen; Dai Hongyi

    2008-01-01

    This paper discusses the concept of controllable subspace for open quantum dynamical systems. It is constructively demonstrated that combining structural features of decoherence-free subspaces with the ability to perform open-loop coherent control on open quantum systems will allow decoherence-free subspaces to be controllable. This is in contrast to the observation that open quantum dynamical systems are not open-loop controllable. To a certain extent, this paper gives an alternative control theoretical interpretation on why decoherence-free subspaces can be useful for quantum computation.

  10. Labetalol Versus Nifedipine as Antihypertensive Treatment for Chronic Hypertension in Pregnancy: A Randomized Controlled Trial.

    Science.gov (United States)

    Webster, Louise M; Myers, Jenny E; Nelson-Piercy, Catherine; Harding, Kate; Cruickshank, J Kennedy; Watt-Coote, Ingrid; Khalil, Asma; Wiesender, Cornelia; Seed, Paul T; Chappell, Lucy C

    2017-11-01

    Data from randomized controlled trials to guide antihypertensive agent choice for chronic hypertension in pregnancy are limited; this study aimed to compare labetalol and nifedipine, additionally assessing the impact of ethnicity on treatment efficacy. Pregnant women with chronic hypertension (12 +0 -27 +6 weeks' gestation) were enrolled at 4 UK centers (August 2014 to October 2015). Open-label first-line antihypertensive treatment was randomly assigned: labetalol- (200-1800 mg/d) or nifedipine-modified release (20-80 mg/d). Analysis included 112 women (98%) who completed the study (labetalol n=55, nifedipine n=57). Maximum blood pressure after randomization was 161/101 mm Hg with labetalol versus 163/105 mm Hg with nifedipine (mean difference systolic: 1.2 mm Hg [-4.9 to 7.2 mm Hg], diastolic: 3.3 mm Hg [-0.6 to 7.3 mm Hg]). Mean blood pressure was 134/84 mm Hg with labetalol and 134/85 mm Hg with nifedipine (mean difference systolic: 0.3 mm Hg [-2.8 to 3.4 mm Hg], and diastolic: -1.9 mm Hg [-4.1 to 0.3 mm Hg]). Nifedipine use was associated with a 7.4-mm Hg reduction (-14.4 to -0.4 mm Hg) in central aortic pressure, measured by pulse wave analysis. No difference in treatment effect was observed in black women (n=63), but a mean 4 mm Hg reduction (-6.6 to -0.8 mm Hg; P =0.015) in brachial diastolic blood pressure was observed with labetalol compared with nifedipine in non-black women (n=49). Labetalol and nifedipine control mean blood pressure to target in pregnant women with chronic hypertension. This study provides support for a larger definitive trial scrutinizing the benefits and side effects of first-line antihypertensive treatment. URL: https://www.isrctn.com. Unique identifier: ISRCTN40973936. © 2017 American Heart Association, Inc.

  11. Omeprazole-Domperidone Fixed Dose Combination vs Omeprazole Monotherapy: A Phase 4, Open-Label, Comparative, Parallel Randomized Controlled Study in Mild to Moderate Gastroesophageal Reflux Disease

    Directory of Open Access Journals (Sweden)

    KY Marakhouski

    2017-05-01

    Full Text Available Aim: To compare the efficacy and safety of omeprazole-domperidone combination vs omeprazole monotherapy in gastroesophageal reflux disease (GERD. Methods: In a comparative, randomized controlled, phase 4 study, outpatients with GERD were randomly allocated to either group 1 (omeprazole 20 mg + domperidone 30 mg or group 2 (omeprazole 20 mg in an equal ratio; 2 capsules daily in the morning were administered for 8 weeks. Results: Sixty patients were enrolled. Esophagitis reversal was observed in 92% patients in group 1 vs 65.2% in group 2. Approximately, 83.3% patients in group 1 vs 43.3% patients in group 2 demonstrated full cupping of reflux symptoms at 8 weeks. Combined therapy resulted in significantly longer period of heartburn-free days (23 vs 12 days on omeprazole. There were no safety concerns. Conclusions: Omeprazole-domperidone combination was more effective than omeprazole alone in providing complete cupping of reflux symptoms and healing of esophagitis in patients with GERD. Both the treatments were well tolerated with few reports of adverse events. Trial registration: This trial is registered with http://clinicaltrials.gov , number NCT02140073.

  12. Employing open/hidden administration in psychotherapy research: A randomized-controlled trial of expressive writing

    Science.gov (United States)

    Tondorf, Theresa; Kaufmann, Lisa-Katrin; Degel, Alexander; Locher, Cosima; Birkhäuer, Johanna; Gerger, Heike; Ehlert, Ulrike

    2017-01-01

    Psychotherapy has been shown to be effective, but efforts to prove specific effects by placebo-controlled trials have been practically and conceptually hampered. We propose that adopting open/hidden designs from placebo research would offer a possible way to establish specificity in psychotherapy. Therefore, we tested the effects of providing opposing treatment rationales in an online expressive writing intervention on affect in healthy subjects. Results indicate that it was possible to conduct the expressive writing intervention both covertly and openly, but that participants in the hidden administration condition did not fully benefit from the otherwise effective expressive writing intervention in the long-run. Effect sizes between open and hidden administration groups were comparable to pre-post effect sizes of the intervention. While this finding is important for the understanding of psychotherapy's effects per se, it also proves that alternative research approaches to establish specificity are feasible and informative in psychotherapy research. Trial registration: German Clinical Trials Register DRKS00009428 PMID:29176768

  13. Some open problems in random matrix theory and the theory of integrable systems

    OpenAIRE

    Deift, Percy

    2007-01-01

    We describe a list of open problems in random matrix theory and integrable systems which was presented at the conference ``Integrable Systems, Random Matrices, and Applications'' at the Courant Institute in May 2006.

  14. Random fiber laser based on artificially controlled backscattering fibers.

    Science.gov (United States)

    Wang, Xiaoliang; Chen, Daru; Li, Haitao; She, Lijuan; Wu, Qiong

    2018-01-10

    The random fiber laser (RFL), which is a milestone in laser physics and nonlinear optics, has attracted considerable attention recently. Most previously reported RFLs are based on distributed feedback of Rayleigh scattering amplified through the stimulated Raman-Brillouin scattering effect in single-mode fibers, which require long-distance (tens of kilometers) single-mode fibers and high threshold, up to watt level, due to the extremely small Rayleigh scattering coefficient of the fiber. We proposed and demonstrated a half-open-cavity RFL based on a segment of an artificially controlled backscattering single-mode fiber with a length of 210 m, 310 m, or 390 m. A fiber Bragg grating with a central wavelength of 1530 nm and a segment of artificially controlled backscattering single-mode fiber fabricated by using a femtosecond laser form the half-open cavity. The proposed RFL achieves thresholds of 25 mW, 30 mW, and 30 mW, respectively. Random lasing at a wavelength of 1530 nm and extinction ratio of 50 dB is achieved when a segment of 5 m erbium-doped fiber is pumped by a 980 nm laser diode in the RFL. A novel RFL with many short cavities has been achieved with low threshold.

  15. 21 CFR 203.38 - Sample lot or control numbers; labeling of sample units.

    Science.gov (United States)

    2010-04-01

    ... numbers; labeling of sample units. (a) Lot or control number required on drug sample labeling and sample... identifying lot or control number that will permit the tracking of the distribution of each drug sample unit... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Sample lot or control numbers; labeling of sample...

  16. Efficacy of 10% sucralfate ointment in the reduction of acute postoperative pain after open hemorrhoidectomy: a prospective, double-blind, randomized, placebo-controlled trial.

    Science.gov (United States)

    Ala, Shahram; Saeedi, Majid; Eshghi, Fariborz; Rafati, Mohamadreza; Hejazi, Vahid; Hadianamrei, Roja

    2013-01-01

    The aim of the present study was to evaluate the efficacy of 10 % sucralfate ointment in the reduction of acute postoperative pain after open hemorrhoidectomy. A total of 48 patients (24 men and 24 women) between 20 and 70 years of age who underwent open hemorrhoidectomy were included in this prospective, double-blind, randomized, controlled trial and were randomly divided into two groups (24 in each group), receiving either sucralfate ointment or placebo immediately after surgery and then every 12 h for 14 days. The primary outcome measure was pain intensity measured by a visual analogue scale at different time points after hemorrhoidectomy. The sucralfate group had significantly less pain than the placebo group at 24th h and the 48th h after hemorrhoidectomy (4 ± 1.14 vs 5.08 ± 0.97; P = 0.001 and 3 ± 0.72 vs 4.41 ± 0.8; P < 0.001, respectively), and they consumed lower amounts of analgesics at the same time intervals (12.50 ± 16.48 vs 21.87 ± 15.30 mg of pethidine; P = 0.047 and 152 ± 23 vs 172 ± 29 mg of diclofenac; P = 0.009, respectively). The same trend continued until the end of the trial. Sucralfate ointment reduced the acute postoperative pain after hemorrhoidectomy.

  17. Performance and economic evaluation of the molecular detection of pathogens for patients with severe infections: the EVAMICA open-label, cluster-randomised, interventional crossover trial.

    Science.gov (United States)

    Cambau, Emmanuelle; Durand-Zaleski, Isabelle; Bretagne, Stéphane; Brun-Buisson, Christian; Cordonnier, Catherine; Duval, Xavier; Herwegh, Stéphanie; Pottecher, Julien; Courcol, René; Bastuji-Garin, Sylvie

    2017-11-01

    Microbiological diagnosis (MD) of infections remains insufficient. The resulting empirical antimicrobial therapy leads to multidrug resistance and inappropriate treatments. We therefore evaluated the cost-effectiveness of direct molecular detection of pathogens in blood for patients with severe sepsis (SES), febrile neutropenia (FN) and suspected infective endocarditis (SIE). Patients were enrolled in a multicentre, open-label, cluster-randomised crossover trial conducted during two consecutive periods, randomly assigned as control period (CP; standard diagnostic workup) or intervention period (IP; additional testing with LightCycler ® SeptiFast). Multilevel models used to account for clustering were stratified by clinical setting (SES, FN, SIE). A total of 1416 patients (907 SES, 440 FN, 69 SIE) were evaluated for the primary endpoint (rate of blood MD). For SES patients, the MD rate was higher during IP than during CP [42.6% (198/465) vs. 28.1% (125/442), odds ratio (OR) 1.89, 95% confidence interval (CI) 1.43-2.50; P analysis of the incremental cost-effectiveness ratio showed weak dominance of intervention in SES patients. Addition of molecular detection to standard care improves MD and thus efficiency of healthcare resource usage in patients with SES. ClinicalTrials.gov registration number: NCT00709358.

  18. Augmentation of light therapy in difficult-to-treat depressed patients: an open-label trial in both unipolar and bipolar patients

    Science.gov (United States)

    Camardese, Giovanni; Leone, Beniamino; Serrani, Riccardo; Walstra, Coco; Di Nicola, Marco; Della Marca, Giacomo; Bria, Pietro; Janiri, Luigi

    2015-01-01

    Objectives We investigated the clinical benefits of bright light therapy (BLT) as an adjunct treatment to ongoing psychopharmacotherapy, both in unipolar and bipolar difficult-to-treat depressed (DTD) outpatients. Methods In an open-label study, 31 depressed outpatients (16 unipolar and 15 bipolar) were included to undergo 3 weeks of BLT. Twenty-five completed the treatment and 5-week follow-up. Main outcome measures Clinical outcomes were evaluated by the Hamilton Depression Rating Scale (HDRS). The Snaith–Hamilton Pleasure Scale and the Depression Retardation Rating Scale were used to assess changes in anhedonia and psychomotor retardation, respectively. Results The adjunctive BLT seemed to influence the course of the depressive episode, and a statistically significant reduction in HDRS scores was reported since the first week of therapy. The treatment was well-tolerated, and no patients presented clinical signs of (hypo)manic switch during the overall treatment period. At the end of the study (after 5 weeks from BLT discontinuation), nine patients (36%, eight unipolar and one bipolar) still showed a treatment response. BLT augmentation also led to a significant improvement of psychomotor retardation. Conclusion BLT combined with the ongoing pharmacological treatment offers a simple approach, and it might be effective in rapidly ameliorating depressive core symptoms of vulnerable DTD outpatients. These preliminary results need to be confirmed in placebo-controlled, randomized, double-blind clinical trial on larger samples. PMID:26396517

  19. Evaluation of a simplified modified Atkins diet for use by parents with low levels of literacy in children with refractory epilepsy: A randomized controlled trial.

    Science.gov (United States)

    Sharma, Suvasini; Goel, Shaiphali; Jain, Puneet; Agarwala, Anuja; Aneja, Satinder

    2016-11-01

    This study was planned to develop and evaluate a simple, easy-to-understand variation of the modified Atkins diet, for use by parents with low levels of literacy in children with refractory epilepsy. This study was conducted in two phases. In the first phase, a simplified version of the modified Atkins diet was developed. In the second phase this was evaluated in children aged 2-14 years who had daily seizures despite the appropriate use of at least two anticonvulsant drugs, in an open-label randomized-controlled-trial. Children were randomized to receive either the simplified modified Atkins diet or no dietary intervention for a period of 3 months with the ongoing anticonvulsant medications being continued unchanged in both the groups. Reduction in seizure frequency was the primary outcome-measure. Data was analyzed using intention to treat approach. Adverse effects were also studied. (Clinical trial identifier NCT0189989). Forty-one children were randomly assigned to the diet-group, and 40 were assigned to the control-group. Two patients discontinued the diet during the study period. The proportion of children with>50% seizure reduction was significantly higher in the diet group as compared to the control group (56.1% vs 7.5%, pliteracy. This diet was found to be feasible, efficacious and well tolerated in children with refractory epilepsy. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. 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.

  1. HIV Salvage Therapy Does Not Require Nucleoside Reverse Transcriptase Inhibitors: A Randomized, Controlled Trial.

    Science.gov (United States)

    Tashima, Karen T; Smeaton, Laura M; Fichtenbaum, Carl J; Andrade, Adriana; Eron, Joseph J; Gandhi, Rajesh T; Johnson, Victoria A; Klingman, Karin L; Ritz, Justin; Hodder, Sally; Santana, Jorge L; Wilkin, Timothy; Haubrich, Richard H

    2015-12-15

    Nucleoside reverse transcriptase inhibitors (NRTIs) are often included in antiretroviral regimens in treatment-experienced patients in the absence of data from randomized trials. To compare treatment success between participants who omit versus those who add NRTIs to an optimized antiretroviral regimen of 3 or more agents. Multicenter, randomized, controlled trial. (ClinicalTrials.gov: NCT00537394). Outpatient HIV clinics. Treatment-experienced patients with HIV infection and viral resistance. Open-label optimized regimens (not including NRTIs) were selected on the basis of treatment history and susceptibility testing. Participants were randomly assigned to omit or add NRTIs. The primary efficacy outcome was regimen failure through 48 weeks using a noninferiority margin of 15%. The primary safety outcome was time to initial episode of a severe sign, symptom, or laboratory abnormality before discontinuation of NRTI assignment. 360 participants were randomly assigned, and 93% completed a 48-week visit. The cumulative probability of regimen failure was 29.8% in the omit-NRTIs group versus 25.9% in the add-NRTIs group (difference, 3.2 percentage points [95% CI, -6.1 to 12.5 percentage points]). No significant between-group differences were found in the primary safety end points or the proportion of participants with HIV RNA level less than 50 copies/mL. No deaths occurred in the omit-NRTIs group compared with 7 deaths in the add-NRTIs group. Unblinded study design, and the study may not be applicable to resource-poor settings. Treatment-experienced patients with HIV infection starting a new optimized regimen can safely omit NRTIs without compromising virologic efficacy. Omitting NRTIs will reduce pill burden, cost, and toxicity in this patient population. National Institute of Allergy and Infectious Diseases, Boehringer Ingelheim, Janssen, Merck, ViiV Healthcare, Roche, and Monogram Biosciences (LabCorp).

  2. Effect of Twice-Yearly Denosumab on Prevention of Bone Mineral Density Loss in De Novo Kidney Transplant Recipients: A Randomized Controlled Trial.

    Science.gov (United States)

    Bonani, M; Frey, D; Brockmann, J; Fehr, T; Mueller, T F; Saleh, L; von Eckardstein, A; Graf, N; Wüthrich, R P

    2016-06-01

    We conducted an open-label, prospective, randomized trial to assess the efficacy and safety of RANKL inhibition with denosumab to prevent the loss of bone mineral density (BMD) in the first year after kidney transplantation. Ninety kidney transplant recipients were randomized 1:1 2 weeks after surgery to receive denosumab (60 mg at baseline and 6 months) or no treatment. After 12 months, total lumbar spine areal BMD (aBMD) increased by 4.6% (95% confidence interval [CI] 3.3-5.9%) in 46 patients in the denosumab group and decreased by -0.5% (95% CI -1.8% to 0.9%) in 44 patients in the control group (between-group difference 5.1% [95% CI 3.1-7.0%], p bone turnover (C-terminal telopeptide of type I collagen, procollagen type I N-terminal propeptide) markedly decreased with denosumab (all p transplantation but was associated with more frequent episodes of urinary tract infection. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  3. Continuous quality improvement interventions to improve long-term outcomes of antiretroviral therapy in women who initiated therapy during pregnancy or breastfeeding in the Democratic Republic of Congo: design of an open-label, parallel, group randomized trial.

    Science.gov (United States)

    Yotebieng, Marcel; Behets, Frieda; Kawende, Bienvenu; Ravelomanana, Noro Lantoniaina Rosa; Tabala, Martine; Okitolonda, Emile W

    2017-04-26

    Despite the rapid adoption of the World Health Organization's 2013 guidelines, children continue to be infected with HIV perinatally because of sub-optimal adherence to the continuum of HIV care in maternal and child health (MCH) clinics. To achieve the UNAIDS goal of eliminating mother-to-child HIV transmission, multiple, adaptive interventions need to be implemented to improve adherence to the HIV continuum. The aim of this open label, parallel, group randomized trial is to evaluate the effectiveness of Continuous Quality Improvement (CQI) interventions implemented at facility and health district levels to improve retention in care and virological suppression through 24 months postpartum among pregnant and breastfeeding women receiving ART in MCH clinics in Kinshasa, Democratic Republic of Congo. Prior to randomization, the current monitoring and evaluation system will be strengthened to enable collection of high quality individual patient-level data necessary for timely indicators production and program outcomes monitoring to inform CQI interventions. Following randomization, in health districts randomized to CQI, quality improvement (QI) teams will be established at the district level and at MCH clinics level. For 18 months, QI teams will be brought together quarterly to identify key bottlenecks in the care delivery system using data from the monitoring system, develop an action plan to address those bottlenecks, and implement the action plan at the level of their district or clinics. If proven to be effective, CQI as designed here, could be scaled up rapidly in resource-scarce settings to accelerate progress towards the goal of an AIDS free generation. The protocol was retrospectively registered on February 7, 2017. ClinicalTrials.gov Identifier: NCT03048669 .

  4. A multicenter, randomized controlled trial of individualized occupational therapy for patients with schizophrenia in Japan

    Science.gov (United States)

    Ohori, Manami; Inagaki, Yusuke; Shimooka, Yuko; Sugimura, Naoya; Ishihara, Ikuyo; Yoshida, Tomotaka

    2018-01-01

    The individualized occupational therapy (IOT) program is a psychosocial program that we developed to facilitate proactive participation in treatment and improve cognitive functioning and other outcomes for inpatients with acute schizophrenia. The program consists of motivational interviewing, self-monitoring, individualized visits, handicraft activities, individualized psychoeducation, and discharge planning. This multicenter, open-labeled, blinded-endpoint, randomized controlled trial evaluated the impact of adding IOT to a group OT (GOT) program as usual for outcomes in recently hospitalized patients with schizophrenia in Japanese psychiatric hospitals setting compared with GOT alone. Patients with schizophrenia were randomly assigned to the GOT+IOT group or the GOT alone group. Among 136 randomized patients, 129 were included in the intent-to-treat population: 66 in the GOT+IOT and 63 in the GOT alone groups. Outcomes were administered at baseline and discharge or 3 months following hospitalization including the Brief Assessment of Cognition in Schizophrenia Japanese version (BACS-J), the Schizophrenia Cognition Rating Scale Japanese version, the Social Functioning Scale Japanese version, the Global Assessment of Functioning scale, the Intrinsic Motivation Inventory Japanese version (IMI-J), the Morisky Medication Adherence Scale-8 (MMAS-8), the Positive and Negative Syndrome Scale (PANSS), and the Japanese version of Client Satisfaction Questionnaire-8 (CSQ-8J). Results of linear mixed effects models indicated that the IOT+GOT showed significant improvements in verbal memory (p IOT demonstrated significant improvements on the CSQ-8J compared with the GOT alone (p IOT program and its effectiveness for improving cognitive impairment and other outcomes in patients with schizophrenia. PMID:29621261

  5. Multimedia educational tools for cognitive surgical skill acquisition in open and laparoscopic colorectal surgery: a randomized controlled trial.

    Science.gov (United States)

    Shariff, U; Kullar, N; Haray, P N; Dorudi, S; Balasubramanian, S P

    2015-05-01

    Conventional teaching in surgical training programmes is constrained by time and cost, and has room for improvement. This study aimed to determine the effectiveness of a multimedia educational tool developed for an index colorectal surgical procedure (anterior resection) in teaching and assessment of cognitive skills and to evaluate its acceptability amongst general surgical trainees. Multimedia educational tools in open and laparoscopic anterior resection were developed by filming multiple operations which were edited into procedural steps and substeps and then integrated onto interactive navigational platforms using Adobe® Flash® Professional CS5 10.1. A randomized controlled trial was conducted on general surgical trainees to evaluate the effectiveness of online multimedia in comparison with conventional 'study day' teaching for the acquisition of cognitive skills. All trainees were assessed before and after the study period. Trainees in the multimedia group evaluated the tools by completing a survey. Fifty-nine trainees were randomized but 27% dropped out, leaving 43 trainees randomized to the multimedia group (n = 25) and study day group (n = 18) who were available for analysis. Posttest scores improved significantly in both groups (P multimedia group was not significantly different from the study day group (6.02 ± 5.12 and 5.31 ± 3.42, respectively; P = 0.61). Twenty-five trainees completed the evaluation survey and experienced an improvement in their decision making (67%) and in factual and anatomical knowledge (88%); 96% agreed that the multimedia tool was a useful additional educational resource. Multimedia tools are effective for the acquisition of cognitive skills in colorectal surgery and are well accepted as an educational resource. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.

  6. Anaesthesiological strategies in elective craniotomy: randomized, equivalence, open trial – The NeuroMorfeo trial

    Directory of Open Access Journals (Sweden)

    Guzzetti Stefano

    2009-04-01

    Full Text Available Abstract Background Many studies have attempted to determine the "best" anaesthetic technique for neurosurgical procedures in patients without intracranial hypertension. So far, no study comparing intravenous (IA with volatile-based neuroanaesthesia (VA has been able to demonstrate major outcome differences nor a superiority of one of the two strategies in patients undergoing elective supratentorial neurosurgery. Therefore, current practice varies and includes the use of either volatile or intravenous anaesthetics in addition to narcotics. Actually the choice of the anaestesiological strategy depends only on the anaesthetists' preferences or institutional policies. This trial, named NeuroMorfeo, aims to assess the equivalence between volatile and intravenous anaesthetics for neurosurgical procedures. Methods/Design NeuroMorfeo is a multicenter, randomized, open label, controlled trial, based on an equivalence design. Patients aged between 18 and 75 years, scheduled for elective craniotomy for supratentorial lesion without signs of intracranial hypertension, in good physical state (ASA I-III and Glasgow Coma Scale (GCS equal to 15, are randomly assigned to one of three anaesthesiological strategies (two VA arms, sevoflurane + fentanyl or sevoflurane + remifentanil, and one IA, propofol + remifentanil. The equivalence between intravenous and volatile-based neuroanaesthesia will be evaluated by comparing the intervals required to reach, after anaesthesia discontinuation, a modified Aldrete score ≥ 9 (primary end-point. Two statistical comparisons have been planned: 1 sevoflurane + fentanyl vs. propofol + remifentanil; 2 sevoflurane + remifentanil vs. propofol + remifentanil. Secondary end-points include: an assessment of neurovegetative stress based on (a measurement of urinary catecholamines and plasma and urinary cortisol and (b estimate of sympathetic/parasympathetic balance by power spectrum analyses of electrocardiographic tracings recorded

  7. Optimum and stepped care standardised antihypertensive treatment with or without renal denervation for resistant hypertension (DENERHTN): a multicentre, open-label, randomised controlled trial.

    Science.gov (United States)

    Azizi, Michel; Sapoval, Marc; Gosse, Philippe; Monge, Matthieu; Bobrie, Guillaume; Delsart, Pascal; Midulla, Marco; Mounier-Véhier, Claire; Courand, Pierre-Yves; Lantelme, Pierre; Denolle, Thierry; Dourmap-Collas, Caroline; Trillaud, Hervé; Pereira, Helena; Plouin, Pierre-François; Chatellier, Gilles

    2015-05-16

    Conflicting blood pressure-lowering effects of catheter-based renal artery denervation have been reported in patients with resistant hypertension. We compared the ambulatory blood pressure-lowering efficacy and safety of radiofrequency-based renal denervation added to a standardised stepped-care antihypertensive treatment (SSAHT) with the same SSAHT alone in patients with resistant hypertension. The Renal Denervation for Hypertension (DENERHTN) trial was a prospective, open-label randomised controlled trial with blinded endpoint evaluation in patients with resistant hypertension, done in 15 French tertiary care centres specialised in hypertension management. Eligible patients aged 18-75 years received indapamide 1·5 mg, ramipril 10 mg (or irbesartan 300 mg), and amlodipine 10 mg daily for 4 weeks to confirm treatment resistance by ambulatory blood pressure monitoring before randomisation. Patients were then randomly assigned (1:1) to receive either renal denervation plus an SSAHT regimen (renal denervation group) or the same SSAHT alone (control group). The randomisation sequence was generated by computer, and stratified by centres. For SSAHT, after randomisation, spironolactone 25 mg per day, bisoprolol 10 mg per day, prazosin 5 mg per day, and rilmenidine 1 mg per day were sequentially added from months two to five in both groups if home blood pressure was more than or equal to 135/85 mm Hg. The primary endpoint was the mean change in daytime systolic blood pressure from baseline to 6 months as assessed by ambulatory blood pressure monitoring. The primary endpoint was analysed blindly. The safety outcomes were the incidence of acute adverse events of the renal denervation procedure and the change in estimated glomerular filtration rate from baseline to 6 months. This trial is registered with ClinicalTrials.gov, number NCT01570777. Between May 22, 2012, and Oct 14, 2013, 1416 patients were screened for eligibility, 106 of those were randomly assigned to treatment

  8. Study design of the influence of SErotonin inhibition on patients with RENAl impairment or diabetes undergoing drug-eluting stent implantation (SERENADE) study: A multicenter, open-label, prospective, randomized study.

    Science.gov (United States)

    Lee, Seung-Ah; Suh, Jung-Won; Park, Jin Joo; Yoon, Chang-Hwan; Cho, Young-Suk; Youn, Tae-Jin; Chae, In-Ho; Kim, Hyo-Soo; Kim, Sang-Hyun; Choi, Dong-Ju

    2015-07-01

    The rates of stent failure after percutaneous coronary intervention have decreased since the introduction of the drug-eluting stent (DES). However, chronic kidney disease (CKD) and diabetes mellitus (DM) remain strong clinical predictors of poor prognosis despite DES implantation. Sarpogrelate, a selective serotonin (5-hydroxytryptamine (HT)2a [5-HT2A]) receptor antagonist, has antiproliferative effects, reducing neointimal hyperplasia and smooth muscle cell proliferation, as well as potent antiplatelet action, inhibiting 5-HT-induced platelet aggregation. However, efficacy and safety data for sarpogrelate in patients with CKD or DM are limited. We aim to determine whether sarpogrelate has beneficial effects in patients with CDK or DM treated with DES implantation. The SERENADE trial is a multicenter, open-label, prospective, randomized study that will test the superiority of triple anti-platelet therapy (TAT; aspirin, clopidogrel, and sarpogrelate) to conventional dual antiplatelet therapy (DAT; aspirin and clopidogrel) in preventing late lumen loss 9 months after the index procedure in patients with CKD or DM. A total of 220 patients diagnosed with coronary artery disease with DM or CKD will be randomized to the TAT or DAT groups (1:1 ratio) after DES implantation. The primary endpoint is late lumen loss at 9 months assessed by quantitative coronary angiography. Secondary efficacy endpoints are composites of major adverse cardiovascular events including cardiac death, nonfatal myocardial infarction, and target lesion revascularization. Secondary safety endpoints are major bleeding events and hepatic or renal impairment. The SERENADE trial will provide insight on the efficacy of adjunctive therapy with sarpogrelate after DES implantation for patients with high-risk profiles such as CKD or DM. National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov NCT02294643). Copyright © 2015. Published by Elsevier Inc.

  9. Unexpected difficulties in randomizing patients in a surgical trial: A prospective study comparing extracorporeal shock wave lithotripsy with open cholecystectomy

    NARCIS (Netherlands)

    P.W. Plaisier; M.Y. Berger (Marjolein); R.L. van der Hul (René); H.G. Nijs (Huub); R. den Toom (Rene); O.T. Terpstra (Onno); H.A. Bruining (Hajo); S.M. Strasberg (S.)

    1994-01-01

    textabstractShortly after extracorporeal shock wave lithotripsy (ESWL) was introduced as a promising new treatment modality for gallstone disease, a randomized controlled study was performed to assess the cost-effectiveness of ESWL compared to open cholecystectomy, the gold standard. During the

  10. An open-label study of sodium oxybate (Xyrem®) in spasmodic dysphonia

    Science.gov (United States)

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

    2016-01-01

    Objective 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. Study Design and Methods 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. Results Sodium oxybate significantly improved voice symptoms (p = 0.001) 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 = 0.03) 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 30–40 min after its intake and lasted about 3.5–4 hours. Conclusion 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. PMID:27808415

  11. Comparison of insulin lispro mix 25 with insulin lispro mix 50 as insulin starter in Chinese patients with type 2 diabetes mellitus (CLASSIFY study): Subgroup analysis of a Phase 4 open-label randomized trial.

    Science.gov (United States)

    Su, Qing; Liu, Chao; Zheng, Hongting; Zhu, Jun; Li, Peng Fei; Qian, Lei; Yang, Wen Ying

    2017-06-01

    Premixed insulins are recommended starter insulins in Chinese patients after oral antihyperglycemic medication (OAM) failure. In the present study, we compared the efficacy and safety of insulin lispro mix 25 (LM25) twice daily (b.i.d.) and insulin lispro mix 50 (LM50) b.i.d. as a starter insulin regimen in Chinese patients with type 2 diabetes mellitus (T2DM) who had inadequate glycemic control with OAMs. The primary efficacy outcome in the present open-label parallel randomized clinical trial was change in HbA1c from baseline to 26 weeks. Patients were randomized in a ratio of 1:  1 to LM25 (n = 80) or LM50 (n = 76). A mixed-effects model with repeated measures was used to analyze continuous variables. The Cochran-Mantel-Haenszel test with stratification factor was used to analyze categorical variables. At the end of the study, LM50 was more efficacious than LM25 in reducing mean HbA1c levels (least-squares [LS] mean difference 0.48; 95 % confidence interval [CI] 0.22, 0.74; P 1). More subjects in the LM50 than LM25 group achieved HbA1c targets of 1) or ≤6.5 % (52.6 % vs 20.0 %; P 1). Furthermore, LM50 was more effective than LM25 at reducing HbA1c in patients with baseline HbA1c, blood glucose excursion, and postprandial glucose greater than or equal to median levels (P ≤ 0.001). The rate and incidence of hypoglycemic episodes and increase in weight at the end of the study were similar between treatment groups. In Chinese patients with T2DM, LM50 was more efficacious than LM25 as a starter insulin. © 2016 The Authors. Journal of Diabetes published by John Wiley & Sons Australia, Ltd and Ruijin Hospital, Shanghai Jiaotong University School of Medicine.

  12. A randomized, open-label, crossover study comparing the effects of oral versus transdermal estrogen therapy on serum androgens, thyroid hormones, and adrenal hormones in naturally menopausal women.

    Science.gov (United States)

    Shifren, Jan L; Desindes, Sophie; McIlwain, Marilyn; Doros, Gheorghe; Mazer, Norman A

    2007-01-01

    To compare the changes induced by oral versus transdermal estrogen therapy on the total and free serum concentrations of testosterone (T), thyroxine (T4), and cortisol (C) and the concentrations of their serum binding globulins sex hormone-binding globulin, thyroxine-binding globulin, and cortisol-binding globulin in naturally menopausal women. Randomized, open-label, crossover. Interventions included a 6-week withdrawal from previous hormone therapy (baseline), followed in randomized order by 12 weeks of oral conjugated equine estrogens (CEE) (0.625 mg/d) and 12 weeks of transdermal estradiol (TD E2) (0.05 mg/d), with oral micronized progesterone (100 mg/d) given continuously during both transdermal estrogen therapy regimens. Twenty-seven women were enrolled in the study, and 25 completed both treatment periods. The mean(SD) percentage changes from baseline of sex hormone-binding globulin, total T, and free T with oral CEE were +132.1% (74.5%), +16.4% (43.8%), and -32.7% (25.9%), respectively, versus +12.0% (25.1%), +1.2% (43.7%), and +1.0% (45.0%) with TD E2. The mean (SD) percentage changes of thyroxine-binding globulin, total T4, and free T4 with oral CEE were +39.9% (20.1%), +28.4% (29.2%), and -10.4% (22.3%), respectively, versus +0.4% (11.1%), -0.7% (16.5%), and +0.2% (26.6%) with TD E2. The mean (SD) percentage changes of cortisol-binding globulin, total C, and free C with oral CEE were +18.0% (19.5%), +29.2% (46.3%), and +50.4% (126.5%), respectively, versus -2.2% (11.3%), -6.7% (30.8%), and +1.8% (77.1%) with TD E2. Concentrations of all hormones and binding globulins were significantly different (P < or = 0.003) during administration of oral versus transdermal estrogen therapy, except for free T4 and free C. Compared with oral CEE, TD E2 exerts minimal effects on the total and free concentrations of T, T4, and C and their binding proteins.

  13. Efficacy of vildagliptin and sitagliptin in lowering fasting plasma glucose: Results of a randomized controlled trial.

    Science.gov (United States)

    Göke, R; Eschenbach, P; Dütting, E D

    2015-06-01

    This study compared the efficacy of vildagliptin and sitagliptin in lowering fasting plasma glucose (FPG) as single-pill combinations (SPCs) with metformin. The randomized crossover, open-label, active-controlled study design assessed the FPG-lowering abilities of a vildagliptin/metformin (50/1000 mg twice daily) SPC compared with a sitagliptin/metformin (50/1000 mg twice daily) SPC after 2 weeks of treatment in 99 type 2 diabetes patients uncontrolled by stable metformin therapy (1000-2000 mg/day). The change in FPG from baseline to day 14 was significantly greater (P vildagliptin [-21.9 mg/dL (SD 27.0)] than with sitagliptin [-14.5 mg/dL (SD 23.0)]. After 14 days of treatment, the mean FPG was 137.8 mg/dL (SD 28.5) with vildagliptin and 140.1mg/dL (SD 26.5) with sitagliptin (P vildagliptin produced a significantly greater reduction in FPG vs baseline compared with sitagliptin, which may translate into clinical relevance. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  14. An Open-Source Label Atlas Correction Tool and Preliminary Results on Huntingtons Disease Whole-Brain MRI Atlases.

    Science.gov (United States)

    Forbes, Jessica L; Kim, Regina E Y; Paulsen, Jane S; Johnson, Hans J

    2016-01-01

    The creation of high-quality medical imaging reference atlas datasets with consistent dense anatomical region labels is a challenging task. Reference atlases have many uses in medical image applications and are essential components of atlas-based segmentation tools commonly used for producing personalized anatomical measurements for individual subjects. The process of manual identification of anatomical regions by experts is regarded as a so-called gold standard; however, it is usually impractical because of the labor-intensive costs. Further, as the number of regions of interest increases, these manually created atlases often contain many small inconsistently labeled or disconnected regions that need to be identified and corrected. This project proposes an efficient process to drastically reduce the time necessary for manual revision in order to improve atlas label quality. We introduce the LabelAtlasEditor tool, a SimpleITK-based open-source label atlas correction tool distributed within the image visualization software 3D Slicer. LabelAtlasEditor incorporates several 3D Slicer widgets into one consistent interface and provides label-specific correction tools, allowing for rapid identification, navigation, and modification of the small, disconnected erroneous labels within an atlas. The technical details for the implementation and performance of LabelAtlasEditor are demonstrated using an application of improving a set of 20 Huntingtons Disease-specific multi-modal brain atlases. Additionally, we present the advantages and limitations of automatic atlas correction. After the correction of atlas inconsistencies and small, disconnected regions, the number of unidentified voxels for each dataset was reduced on average by 68.48%.

  15. Effect of Magnesium Supplements on Insulin Secretion After Kidney Transplantation: A Randomized Controlled Trial.

    Science.gov (United States)

    Van Laecke, Steven; Caluwe, Rogier; Huybrechts, Inge; Nagler, Evi V; Vanholder, Raymond; Peeters, Patrick; Van Vlem, Bruno; Van Biesen, Wim

    2017-08-29

    BACKGROUND Hypomagnesemia is associated with a disturbed glucose metabolism. Insulin hypo-secretion predicts diabetes in the general population and in transplant recipients. We aimed to assess whether magnesium improves insulin secretion and glycemic control after transplantation in prevalent hypomagnesemic kidney transplant recipients. MATERIAL AND METHODS We conducted an open-label, randomized, parallel-group study. Eligible participants were adults more than 4 months after kidney transplantation on tacrolimus with persisting serum magnesium concentrations food-frequency questionnaire. All analyses were done on an intention-to-treat basis. RESULTS Magnesium with a mean daily dose of 688±237mg in the treatment group failed to lead to significant differences between the 2 groups in FPIR, fasting glucose, HbA1c, or HOMA-IR. Persisting hypomagnesemia was very common and associated with more insulin hypo-secretion, glucose intolerance, and lower dietary magnesium intake (142±56 versus 202±90 mg; p=0.015) as compared to patients with a rise in serum magnesium over 6 months. CONCLUSIONS Magnesium supplementation does not improve insulin secretion in stable hypomagnesemic kidney transplant recipients on tacrolimus. Persisting hypomagnesemia is associated with impaired glucose tolerance, insulin hypo-secretion, and dietary factors.

  16. BP-C1 in the treatment of patients with stage IV breast cancer: a randomized, double-blind, placebo-controlled multicenter study and an additional open-label treatment phase

    Directory of Open Access Journals (Sweden)

    Larsen S

    2014-11-01

    Full Text Available Stig Larsen,1 Kritiya Butthongkomvong,2 Alexey Manikhas,3 Ekaterina Trishkina,4 Elena Poddubuskaya,5 Marina Matrosova,6 Vichien Srimuninnimit,7 Steen Lindkær-Jensen81Department of Controlled Clinical Trials and Biostatistics, Centre for Epidemiology and Biostatistics, University of Life Science, Oslo, Norway; 2Udonthani Cancer Hospital, Udonthani, Thailand; 3Department of Oncology, City Clinical Oncology, Dispensary, St Petersburg, Russia; 4Department of Oncology, Leningrad Regional Oncology Centre, St Petersburg, Russia; 5Department of Oncology, Unit of Russian Academy of Medical Science, Moscow, Russia; 6Department of Oncology, N Novgorod Regional Oncology Dispensary, Novgorod, Russia; 7Division of Medical Oncology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand; 8Department of Surgery and Cancer, Imperial College, Hammersmith Hospital, London, UKAbstract: The aims were to compare the efficacy and tolerability of a new benzene-poly-carboxylic acids complex with cis-diammineplatinum (II dichloride (BP-C1 versus placebo and to investigate the long-term tolerability of BP-C1 in the treatment of patients with metastatic breast cancer.Material and methods: A randomized, double-blind, placebo-controlled multicenter study was performed with a semi-crossover design. Patients allocated to placebo switched to BP-C1 after 32 days of treatment. Patients who completed 32 days of BP-C1 treatment were offered the opportunity to continue on BP-C1 for an additional 32 days in an open-label extension. Patients were then followed up for another 28 days. Thirty patients were given daily intramuscular injections of 0.035 mg/kg of body weight BP-C1 or placebo for 32 days. Biochemistry, hematology, National Cancer Institute Common Terminology Criteria for Adverse Events (CTC-NCI, European Organisation for Research and Treatment of Cancer quality of life questionnaire (QOL-C30 and the breast-cancer–specific BR23 data were recorded at

  17. An open randomized controlled study comparing an online text-based scenario and a serious game by Belgian and Swiss pharmacy students.

    Science.gov (United States)

    Berger, Jérôme; Bawab, Noura; De Mooij, Jeremy; Sutter Widmer, Denise; Szilas, Nicolas; De Vriese, Carine; Bugnon, Olivier

    2018-03-01

    To compare online learning tools, looped, branch serious game (SG) and linear text-based scenario (TBS), among a sample of Belgian and Swiss pharmacy students. Open randomized controlled study. The lesson was based on the case of a benign cough in a healthy child. A randomized sample of 117 students: only the Swiss students had attended a previous lecture on coughs. Participation rate, pre- and post-experience Likert scales and students' clinical knowledge were measured. Our primary hypothesis was demonstrated: students favored the SG even if navigation was rated as more complex, and students who performed the SG better understood the aim of pharmacist triage in case of cough. The influence of the SG appeared to be linked to the presence of a previous lecture in the curriculum. SG and TBS are effective to teach pharmacist triage. Higher SG complexity should be used to teach the aim of pharmacist triage in the case of a specific disease and could be an alternative to simulated patients. A simpler TBS does not require a previous lecture and a debriefing to be fully effective. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. 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.

    Science.gov (United States)

    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.

  19. Tolerability and safety of Souvenaid in patients with mild Alzheimer's disease: results of multi-center, 24-week, open-label extension study.

    Science.gov (United States)

    Olde Rikkert, Marcel G M; Verhey, Frans R; Blesa, Rafael; von Arnim, Christine A F; Bongers, Anke; Harrison, John; Sijben, John; Scarpini, Elio; Vandewoude, Maurits F J; Vellas, Bruno; Witkamp, Renger; Kamphuis, Patrick J G H; Scheltens, Philip

    2015-01-01

    The medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect, is designed to improve synapse formation and function in patients with Alzheimer's disease (AD). Two double-blind randomized controlled trials (RCT) with Souvenaid of 12 and 24 week duration (Souvenir I and Souvenir II) showed that memory performance was improved in drug-naïve mild AD patients, whereas no effects on cognition were observed in a 24-week RCT (S-Connect) in mild to moderate AD patients using AD medication. Souvenaid was well-tolerated in all RCTs. In this 24-week open-label extension (OLE) study to the 24-week Souvenir II RCT, long-term safety and intake adherence of the medical food Souvenaid was evaluated. Patients with mild AD (n = 201) received Souvenaid once-daily during the OLE. Main outcome parameters were safety and product intake adherence. The memory domain z-score from a revised neuropsychological test battery was continued as exploratory parameter. Compared to the RCT, a similar (low) incidence and type of adverse events was observed, being mainly (68.3%) of mild intensity. Pooled data (RCT and OLE) showed that 48-week use of Souvenaid was well tolerated with high intake adherence (96.1%). Furthermore, a significant increase in the exploratory memory outcome was observed in both the active-active and control-active groups during Souvenaid intervention. Souvenaid use for up to 48-weeks was well tolerated with a favorable safety profile and high intake adherence. The findings in this OLE study warrant further investigation toward the long-term safety and efficacy of Souvenaid in a well-controlled, double-blind RCT.

  20. UNEXPECTED DIFFICULTIES IN RANDOMIZING PATIENTS IN A SURGICAL TRIAL - A PROSPECTIVE-STUDY COMPARING EXTRACORPOREAL SHOCK-WAVE LITHOTRIPSY WITH OPEN CHOLECYSTECTOMY

    NARCIS (Netherlands)

    PLAISIER, PW; BERGER, MY; VANDERHUL, RL; NIJS, HGT; DENTOOM, R; TERPSTRA, OT; BRUINING, HA

    1994-01-01

    Shortly after extracorporeal shock wave lithotripsy (ESWL) was introduced as a promising new treatment modality for gallstone disease, a randomized controlled study was performed to assess the cost-effectiveness of ESWL compared to open cholecystectomy, the gold standard. During the performance of

  1. Health-related quality of life and functional outcomes from a randomized-withdrawal study of long-term lisdexamfetamine dimesylate treatment in children and adolescents with attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Banaschewski, Tobias; Johnson, Mats; Lecendreux, Michel; Zuddas, Alessandro; Adeyi, Ben; Hodgkins, Paul; Squires, Liza A; Coghill, David R

    2014-12-01

    The stimulant prodrug lisdexamfetamine dimesylate (LDX) is an effective and generally well tolerated treatment for the symptoms of attention-deficit/hyperactivity disorder (ADHD). Positive impacts of LDX on health-related quality of life and functional impairment have previously been demonstrated in a 7-week, randomized, double-blind, placebo-controlled, phase III study in children and adolescents in Europe. Maintenance of these broad benefits, as well as symptomatic control, is a key goal of long-term management of ADHD. Secondary objectives of this multinational study in children and adolescents with ADHD were to assess the long-term maintenance of effectiveness of LDX in improving health-related quality of life and reducing functional impairment, as gauged using the Child Health and Illness Profile-Child Edition: Parent Report Form (CHIP-CE: PRF) and the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P), respectively. Patients aged 6-17 years with diagnosed ADHD and a baseline ADHD Rating Scale IV total score of at least 28 were enrolled from the previous European study and from US sites. Patients who completed an open-label LDX treatment period of at least 26 weeks were randomized (1:1) to continue on their optimized dose of LDX or to switch to placebo for a 6-week, double-blind, withdrawal period. Parents completed CHIP-CE: PRF and WFIRS-P questionnaires at weeks 0, 8 and 26 of the open-label period and at weeks 0 and 6 of the randomized-withdrawal period, or at early termination. The endpoint of each period was defined as the last visit with valid data. Effect sizes were the difference (LDX minus placebo) in least-squares (LS)-mean change from baseline to endpoint divided by root-mean-square error. P values were nominal and not adjusted for multiple comparisons. The open-label and randomized full analysis sets comprised 262 and 153 (LDX n = 76; placebo n = 77) patients, respectively. Mean pretreatment CHIP-CE: PRF T-scores were more than one

  2. Sodium Restriction in Patients With CKD : A Randomized Controlled Trial of Self-management Support

    NARCIS (Netherlands)

    Meuleman, Yvette; Hoekstra, Tiny; Dekker, Friedo W.; Navis, Gerjan; Vogt, Liffert; van der Boog, Paul J. M.; Bos, Willem Jan W.; van Montfrans, Gert A.; van Dijk, Sandra

    Background: To evaluate the effectiveness and sustainability of self-managed sodium restriction in patients with chronic kidney disease. Study Design: Open randomized controlled trial. Setting & Participants: Patients with moderately decreased kidney function from 4 hospitals in the Netherlands.

  3. Long-Term Effects of Goshajinkigan in Prevention of Diabetic Complications: A Randomized Open-Labeled Clinical Trial

    Directory of Open Access Journals (Sweden)

    K. Watanabe

    2014-01-01

    Full Text Available Objective. This clinical trial was designed to investigate whether goshajinkigan reduces the onset of diabetic complications or not. Materials and Methods. A total of 332 type 2 diabetic mellitus patients were registered from 9 clinical centers from March 2000 to August 2007. Patients were randomly assigned to take goshajinkigan extract powder, 2.5 grams for 3 times a day or no kampo therapy, additionally to the regular treatment. The primary endpoints were the onset of macrovascular diseases or progression of nephropathy or retinopathy. Statistical analysis was performed by the intention-to-treat method. Results. After 5 years of observation, 116 patients were submitted to analysis. Among them, no macrovascular events were observed in both groups. Although 43 participants had upstaging of retinopathy or nephropathy in total, there was no significant difference between goshajinkigan group and control group. Deterioration of ankle reflex was suppressed in goshajinkigan group. Also glycated hemoglobin, and fasting plasma glucose were decreased in the goshajinkigan group. Conclusion. Although the power of analysis was too low to demonstrate any effects of goshajinkigan on the progression of macrovascular diseases, retinopathy or nephropathy, goshajinkigan may be beneficial for diabetic neuropathy and glycemic control.

  4. Milrinone therapy for enterovirus 71-induced pulmonary edema and/or neurogenic shock in children: a randomized controlled trial.

    Science.gov (United States)

    Chi, Chia-Yu; Khanh, Truong Huu; Thoa, Le Phan Kim; Tseng, Fan-Chen; Wang, Shih-Min; Thinh, Le Quoc; Lin, Chia-Chun; Wu, Han-Chieh; Wang, Jen-Ren; Hung, Nguyen Thanh; Thuong, Tang Chi; Chang, Chung-Ming; Su, Ih-Jen; Liu, Ching-Chuan

    2013-07-01

    Enterovirus 71-induced brainstem encephalitis with pulmonary edema and/or neurogenic shock (stage 3B) is associated with rapid mortality in children. In a small pilot study, we found that milrinone reduced early mortality compared with historical controls. This prospective, randomized control trial was designed to provide more definitive evidence of the ability of milrinone to reduce the 1-week mortality of stage 3B enterovirus 71 infections. Prospective, unicenter, open-label, randomized, controlled study. Inpatient ward of a large tertiary teaching hospital in Ho Chi Minh City, Vietnam. Children (≤ 18 yr old) admitted with proven enterovirus 71-induced pulmonary edema and/or neurogenic shock. Patients were randomly assigned to receive intravenous milrinone (0.5 μg/kg/min) (n = 22) or conventional management (n = 19). Both groups received dopamine or dobutamine and intravenous immunoglobulin. The primary endpoint was 1-week mortality. The secondary endpoints included length of ventilator dependence and hospital stay and adverse events. The median age was 2 years with a predominance of boys in both groups. The 1-week mortality was significantly lower, 18.2% (4/22) in the milrinone compared with 57.9% (11/19) in the conventional management group (relative risk = 0.314 [95% CI, 0.12-0.83], p = 0.01). The median duration of ventilator-free days was longer in the milrinone treatment group (p = 0.01). There was no apparent neurologic sequela in the survivors in either group, and no drug-related adverse events were documented. Milrinone significantly reduced the 1-week mortality of enterovirus 71-induced pulmonary edema and/or neurogenic shock without adverse effects. Further studies are needed to determine whether milrinone might be useful to prevent progression of earlier stages of brainstem encephalitis.

  5. Early weight bearing versus delayed weight bearing in medial opening wedge high tibial osteotomy: a randomized controlled trial.

    Science.gov (United States)

    Lansdaal, Joris Radboud; Mouton, Tanguy; Wascher, Daniel Charles; Demey, Guillaume; Lustig, Sebastien; Neyret, Philippe; Servien, Elvire

    2017-12-01

    The need for a period of non-weight bearing after medial opening wedge high tibial osteotomy remains controversial. It is hypothesized that immediate weight bearing after medial opening wedge high tibial osteotomy would have no difference in functional scores at one year compared to delayed weight bearing. Fifty patients, median age 54 years (range 40-65), with medial compartment osteoarthritis, underwent a medial opening wedge high tibial osteotomy utilizing a locking plate without bone grafting. Patients were randomized into an Immediate or a Delayed (2 months) weight bearing group. All patients were assessed at one-year follow-up and the two groups compared. The primary outcome measure was the IKS score. Secondary outcome measures included the IKDC score, the VAS pain score and rate of complications. The functional scores significantly improved in both groups. The IKS score increased from 142 ± 31 to 171 ± 26 in the Immediate group (p bearing after medial opening wedge high tibial osteotomy had no effect on functional scores at 1 year follow-up and did not significantly increase the complication rate. Immediate weight bearing after medial opening wedge high tibial osteotomy appears to be safe and can allow some patients a quicker return to activities of daily living and a decreased convalescence period. II.

  6. Attitude and Behavior Factors Associated with Front-of-Package Label Use with Label Users Making Accurate Product Nutrition Assessments.

    Science.gov (United States)

    Roseman, Mary G; Joung, Hyun-Woo; Littlejohn, Emily I

    2018-05-01

    Front-of-package (FOP) labels are increasing in popularity on retail products. Reductive FOP labels provide nutrient-specific information, whereas evaluative FOP labels summarize nutrient information through icons. Better understanding of consumer behavior regarding FOP labels is beneficial to increasing consumer use of nutrition labeling when making grocery purchasing decisions. We aimed to determine FOP label format effectiveness in aiding consumers at assessing nutrient density of food products. In addition, we sought to determine relationships between FOP label use and attitude toward healthy eating, diet self-assessment, self-reported health and nutrition knowledge, and label and shopping behaviors. A between-subjects experimental design was employed. Participants were randomly assigned to one of four label conditions: Facts Up Front, Facts Up Front Extended, a binary symbol, and no-label control. One hundred sixty-one US primary grocery shoppers, aged 18 to 69 years. Participants were randomly invited to the online study. Participants in one of four label condition groups viewed three product categories (cereal, dairy, and snacks) with corresponding questions. Adults' nutrition assessment of food products based on different FOP label formats, along with label use and attitude toward healthy eating, diet self-assessment, self-reported health and nutrition knowledge, and label and shopping behaviors. Data analyses included descriptive statistics, χ 2 tests, and logistical regression. Significant outcomes were set to α=.05. Participants selected the more nutrient-dense product in the snack food category when it contained an FOP label. Subjective health and nutrition knowledge and frequency of selecting food for healthful reasons were associated with FOP label use (P<0.01 and P<0.05, respectively). Both Facts Up Front (reductive) and binary (evaluative) FOP labels appear effective for nutrition assessment of snack products compared with no label. Specific

  7. 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.

  8. Laserlight cues for gait freezing in Parkinson's disease: an open-label study.

    Science.gov (United States)

    Donovan, S; Lim, C; Diaz, N; Browner, N; Rose, P; Sudarsky, L R; Tarsy, D; Fahn, S; Simon, D K

    2011-05-01

    Freezing of gait (FOG) and falls are major sources of disability for Parkinson's disease (PD) patients, and show limited responsiveness to medications. We assessed the efficacy of visual cues for overcoming FOG in an open-label study of 26 patients with PD. The change in the frequency of falls was a secondary outcome measure. Subjects underwent a 1-2 month baseline period of use of a cane or walker without visual cues, followed by 1 month using the same device with the laserlight visual cue. The laserlight visual cue was associated with a modest but significant mean reduction in FOG Questionnaire (FOGQ) scores of 1.25 ± 0.48 (p = 0.0152, two-tailed paired t-test), representing a 6.6% improvement compared to the mean baseline FOGQ scores of 18.8. The mean reduction in fall frequency was 39.5 ± 9.3% with the laserlight visual cue among subjects experiencing at least one fall during the baseline and subsequent study periods (p = 0.002; two-tailed one-sample t-test with hypothesized mean of 0). Though some individual subjects may have benefited, the overall mean performance on the timed gait test (TGT) across all subjects did not significantly change. However, among the 4 subjects who underwent repeated testing of the TGT, one showed a 50% mean improvement in TGT performance with the laserlight visual cue (p = 0.005; two-tailed paired t-test). This open-label study provides evidence for modest efficacy of a laserlight visual cue in overcoming FOG and reducing falls in PD patients. Copyright © 2010 Elsevier Ltd. All rights reserved.

  9. Intradialytic parenteral nutrition in maintenance hemodialysis patients suffering from protein-energy wasting. Results of a multicenter, open, prospective, randomized trial.

    Science.gov (United States)

    Marsen, Tobias A; Beer, Justinus; Mann, Helmut

    2017-02-01

    Protein-energy wasting (PEW) is increasingly becoming a clinical problem in maintenance hemodialysis patients and guidelines call for nutritional interventions. Serum prealbumin (transthyretin) represents a critical nutritional marker positively correlated with patient survival and negatively correlated with morbidity. Nutritional counseling, oral supplementation as well as intradialytic parenteral nutrition (IDPN) are recommended to fight PEW, however clinical trials on their use are scarce. We conducted a prospective, multicenter, randomized, open-label, controlled, parallel-group Phase IV clinical trial in 107 maintenance hemodialysis patients suffering from PEW to assess the impact of IDPN on prealbumin and other biochemical and clinical parameters reflecting nutritional status. Patients randomized to the intervention group received standardized nutritional counseling plus IDPN three times weekly over 16 weeks followed by a treatment-free period of 12 weeks. The control group received standardized nutritional counseling only. Main trial inclusion criteria included moderate to severe malnutrition (SGA score B or C), maintenance hemodialysis therapy (3 times per week) for more than six months, and presence of two out of the following three criteria: albumin 30 mg/L at week 16 (48.7% vs. 31.8%). Prealbumin response to IDPN therapy was more prominent in patients suffering from moderate malnutrition (SGA score B) compared to patients with severe malnutrition (SGA score C). The results of this trial demonstrate for the first time that IDPN therapy, given three times weekly in a 16-week short-term intervention, results in a statistically significant and clinically relevant increase in mean serum prealbumin, a surrogate marker for outcome and survival in hemodialysis patients suffering from PEW, and is superior to nutritional counseling. Clinical trial registry:www.clinicaltrials.gov (NCT00501956). Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights

  10. Lidocaine lozenges for pharyngeal anesthesia during upper gastrointestinal endoscopy: A randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Avinash Supe

    2014-01-01

    Full Text Available Background and Objectives: A novel lozenge formulation with advantages of ease of drug administration, palatable taste and improved patient compliance could be the preferred mode of topical pharyngeal anesthesia during upper gastrointestinal endoscopy (UGE. This randomized, open-label, active-controlled study was conducted to evaluate the efficacy and safety of lidocaine lozenges versus lidocaine spray in the diagnostic gastroduodenal endoscopy in Indian patients. Subjects and Methods: Two hundred and forty-seven patients of either sex (18-80 years undergoing diagnostic gastroduodenal endoscopy were randomized either to; lidocaine lozenge 200 mg or lidocaine spray 200 mg to be applied as a single dose before gastroduodenal endoscopy. Ease of procedure, level of gag reflex, ease of application of the local anesthetic, and investigators global assessment were the primary efficacy endpoints. Need for rescue medication and patient′s global assessment were secondary efficacy endpoints. The incidence of any adverse event was the safety endpoint. Between groups, comparison was done by using appropriate statistical test. Results: Investigator reported significantly lesser procedural difficulty (P = 0.0007 and suppressed gag reflex (P < 0.0001 during UGE with lidocaine lozenge compared to spray. Ease of application of local anesthetic was reported easy in significantly more patients as compared with lidocaine spray (P = 0.001. Global assessment by patient and physician was favorable toward lozenge. Incidences of adverse events were similar in both the groups. Conclusions: The study suggests that lidocaine lozenges are an easier way of applying local oropharyngeal anesthesia, produces better suppression of gag reflex and makes the procedure easier when compared with lidocaine spray.

  11. Tipepidine in children with attention deficit/hyperactivity disorder: a 4-week, open-label, preliminary study

    Directory of Open Access Journals (Sweden)

    Sasaki T

    2014-01-01

    Full Text Available Tsuyoshi Sasaki,1,2 Kenji Hashimoto,3 Masumi Tachibana,1 Tsutomu Kurata,1 Keiko Okawada,1 Maki Ishikawa,1 Hiroshi Kimura,2 Hideki Komatsu,2 Masatomo Ishikawa,2 Tadashi Hasegawa,2 Akihiro Shiina,1 Tasuku Hashimoto,2 Nobuhisa Kanahara,3 Tetsuya Shiraishi,2 Masaomi Iyo1–31Department of Child Psychiatry, Chiba University Hospital, 2Department of Psychiatry, Chiba University Graduate School of Medicine, 3Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, JapanBackground: Tipepidine (3-[di-2-thienylmethylene]-1-methylpiperidine has been used solely as a nonnarcotic antitussive in Japan since 1959. The safety of tipepidine in children and adults has already been established. It is reported that tipepidine inhibits G-protein-coupled inwardly rectifying potassium (GIRK-channel currents. The inhibition of GIRK channels by tipepidine is expected to modulate the level of monoamines in the brain. We put forward the hypothesis that tipepidine can improve attention deficit/hyperactivity disorder (ADHD symptoms by modulating monoaminergic neurotransmission through the inhibition of GIRK channels. The purpose of this open-label trial was to confirm whether treatment with tipepidine can improve symptoms in pediatric patients with ADHD.Subjects and methods: This was a 4-week, open-label, proof-of-efficacy pilot study for pediatric subjects with ADHD. Ten pediatric ADHD subjects (70% male; mean age, 9.9 years; combined [inattentive and hyperactive/impulsive] subtype, n=7; inattentive subtype, n=3; hyperimpulsive subtype, n=0 received tipepidine hibenzate taken orally at 30 mg/day for 4 weeks. All subjects were assessed using the ADHD Rating Scale IV (ADHD-RS, Japanese version, and the Das–Naglieri Cognitive Assessment System (DN-CAS, Japanese version.Results: A comparison of baseline scores and 4-week end-point scores showed that all the ADHD-RS scores (total scores, hyperimpulsive subscores, and inattentive subscores

  12. Improving labeling efficiency in automatic quality control of MRSI data.

    Science.gov (United States)

    Pedrosa de Barros, Nuno; McKinley, Richard; Wiest, Roland; Slotboom, Johannes

    2017-12-01

    To improve the efficiency of the labeling task in automatic quality control of MR spectroscopy imaging data. 28'432 short and long echo time (TE) spectra (1.5 tesla; point resolved spectroscopy (PRESS); repetition time (TR)= 1,500 ms) from 18 different brain tumor patients were labeled by two experts as either accept or reject, depending on their quality. For each spectrum, 47 signal features were extracted. The data was then used to run several simulations and test an active learning approach using uncertainty sampling. The performance of the classifiers was evaluated as a function of the number of patients in the training set, number of spectra in the training set, and a parameter α used to control the level of classification uncertainty required for a new spectrum to be selected for labeling. The results showed that the proposed strategy allows reductions of up to 72.97% for short TE and 62.09% for long TE in the amount of data that needs to be labeled, without significant impact in classification accuracy. Further reductions are possible with significant but minimal impact in performance. Active learning using uncertainty sampling is an effective way to increase the labeling efficiency for training automatic quality control classifiers. Magn Reson Med 78:2399-2405, 2017. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

  13. Prophylactic antibiotics after acute stroke for reducing pneumonia in patients with dysphagia (STROKE-INF): a prospective, cluster-randomised, open-label, masked endpoint, controlled clinical trial.

    Science.gov (United States)

    Kalra, Lalit; Irshad, Saddif; Hodsoll, John; Simpson, Matthew; Gulliford, Martin; Smithard, David; Patel, Anita; Rebollo-Mesa, Irene

    2015-11-07

    Post-stroke pneumonia is associated with increased mortality and poor functional outcomes. This study assessed the effectiveness of antibiotic prophylaxis for reducing pneumonia in patients with dysphagia after acute stroke. We did a prospective, multicentre, cluster-randomised, open-label controlled trial with masked endpoint assessment of patients older than 18 years with dysphagia after new stroke recruited from 48 stroke units in the UK, accredited and included in the UK National Stroke Audit. We excluded patients with contraindications to antibiotics, pre-existing dysphagia, or known infections, or who were not expected to survive beyond 14 days. We randomly assigned the units (1:1) by computer to give either prophylactic antibiotics for 7 days plus standard stroke unit care or standard stroke unit care only to patients clustered in the units within 48 h of stroke onset. We did the randomisation with minimisation to stratify for number of admissions and access to specialist care. Patient and staff who did the assessments and analyses were masked to stroke unit allocation. The primary outcome was post-stroke pneumonia in the first 14 days, assessed with both a criteria-based, hierarchical algorithm and by physician diagnosis in the intention-to-treat population. Safety was also analysed by intention to treat. This trial is closed to new participants and is registered with isrctn.com, number ISRCTN37118456. Between April 21, 2008, and May 17, 2014, we randomly assigned 48 stroke units (and 1224 patients clustered within the units) to the two treatment groups: 24 to antibiotics and 24 to standard care alone (control). 11 units and seven patients withdrew after randomisation before 14 days, leaving 1217 patients in 37 units for the intention-to-treat analysis (615 patients in the antibiotics group, 602 in control). Prophylactic antibiotics did not affect the incidence of algorithm-defined post-stroke pneumonia (71 [13%] of 564 patients in antibiotics group vs 52

  14. Dynamic Output Feedback Control for Nonlinear Networked Control Systems with Random Packet Dropout and Random Delay

    Directory of Open Access Journals (Sweden)

    Shuiqing Yu

    2013-01-01

    Full Text Available This paper investigates the dynamic output feedback control for nonlinear networked control systems with both random packet dropout and random delay. Random packet dropout and random delay are modeled as two independent random variables. An observer-based dynamic output feedback controller is designed based upon the Lyapunov theory. The quantitative relationship of the dropout rate, transition probability matrix, and nonlinear level is derived by solving a set of linear matrix inequalities. Finally, an example is presented to illustrate the effectiveness of the proposed method.

  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. 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.

  17. Effects of Food on the Pharmacokinetics of Omega-3-Carboxylic Acids in Healthy Japanese Male Subjects: A Phase I, Randomized, Open-label, Three-period, Crossover Trial.

    Science.gov (United States)

    Shimada, Hitoshi; Nilsson, Catarina; Noda, Yoshinori; Kim, Hyosung; Lundström, Torbjörn; Yajima, Toshitaka

    2017-09-01

    Omega-3-carboxylic acids (OM3-CA) contain omega-3 free fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), as carboxylic acids. Food intake is known to affect the bioavailability of ethyl ester fatty acid formulations. We conducted a phase I study to investigate the effects of the timing of OM3-CA administration relative to food intake on the pharmacokinetics of EPA and DHA. In this randomized, open-label, three-period crossover study, Japanese healthy male subjects were administered 4×1 g OM3-CA capsules with continued fasting, before a meal, or after a meal. All subjects fasted for ≥10 h prior to drug/meal administration. The primary objective was to examine the effect of meal timing on the pharmacokinetics of EPA and DHA after OM3-CA administration. The secondary objectives were to examine the safety and tolerability of OM3-CA. A total of 42 Japanese subjects was enrolled in the study. The baseline-adjusted maximum concentration and area under the concentration-time curve from 0 to 72 h for EPA, DHA, and EPA +DHA were lower in the fasting and before meal conditions than in the after meal condition. The maximum total EPA, total DHA, and total EPA+DHA concentrations were reached later when administered in fasting conditions than in fed conditions, indicating slower absorption in fasting conditions. Diarrhea was reported by five, six, and no subjects in the fasting, before meal, and after meal conditions, respectively. The timing of OM3-CA administration relative to food intake influences the systemic bioavailability of EPA and DHA in healthy Japanese male subjects. NCT02372344.

  18. 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.

  19. Five-year extension of a clinical trial comparing the EX-PRESS glaucoma filtration device and trabeculectomy in primary open-angle glaucoma

    NARCIS (Netherlands)

    de Jong, Leo; Lafuma, Antoine; Aguadé, Anne-Sophie; Berdeaux, Gilles

    2011-01-01

    This study compared the efficacy of the EX-PRESS(®) glaucoma filtration device and trabeculectomy in primary open-angle glaucoma up to five years after surgery. Patients from a previously reported randomized, open-label, parallel-arm clinical trial in which 78 patients received either the EX-PRESS

  20. Six week open-label reboxetine treatment in children and adolescents with attention deficit hyperactivity disorder

    Directory of Open Access Journals (Sweden)

    Arabgol F

    2007-10-01

    Full Text Available Background: Attention Deficit Hyperactivity Disorder (ADHD is a common psychiatric disorder among children and adolescents. This disorder causes difficulties in academic, behavioral, emotional, social and family performance. Stimulants show robust efficacy and a good safety profile in children with this disorder, but a significant percent of ADHD children do not respond adequately or cannot tolerate the associated adverse effects with stimulants. Such difficulties highlight the need for alternative safe and effective medications in the treatment of this disorder. This open-label study assessed the effectiveness of reboxetine, a selective norepinephrine reuptake inhibitor, in children and adolescents with attention deficit hyperactivity disorder (ADHD."nMethods: Fifteen child and adolescent outpatients, aged 7 to 16 (Mean± SD=9.72±2.71 years, diagnosed with ADHD were enrolled in a six open-label study with reboxetine 4-6 mg/d. The principal measure of the outcome was the teacher and parent Attention Deficit Hyperactive Disorder Rating Scale (ADHD Rating Scale. Patients were assessed by a child psychiatrist at baseline, 2, 4 and 6 weeks of the medication started. Side effects questionnaire was used to detect side effects of reboxetine. Repeated measures Analysis of variance (ANOVA was done for comparison of Teacher and Parent ADHD Rating Scale scores during the intervention."nResults: Twelve of 15 (80% participants completed the treatment protocol. A significant decrease in ADHD symptoms on teacher (p=0.04 and parent (p=0.003 ADHD rating scale was noted. Adverse effects were mild to moderate in severity. The most common adverse effects were drowsiness/sedation and appetite decrease."nConclusion: The results of the current study suggest the effectiveness of reboxetine in the treatment of ADHD in children and adolescents. Double-blind, placebo-controlled studies and larger sample size with long duration of intervention are indicated to rigorously

  1. Health-related quality of life after laparoscopic and open surgery for rectal cancer in a randomized trial

    DEFF Research Database (Denmark)

    Andersson, J; Angenete, E; Gellerstedt, M

    2013-01-01

    Previous studies comparing laparoscopic and open surgical techniques have reported improved health-related quality of life (HRQL). This analysis compared HRQL 12¿months after laparoscopic versus open surgery for rectal cancer in a subset of a randomized trial.......Previous studies comparing laparoscopic and open surgical techniques have reported improved health-related quality of life (HRQL). This analysis compared HRQL 12¿months after laparoscopic versus open surgery for rectal cancer in a subset of a randomized trial....

  2. Early conversion from calcineurin inhibitor- to everolimus-based therapy following kidney transplantation : Results of the randomized ELEVATE trial

    NARCIS (Netherlands)

    de Fijter, Johan W; Holdaas, Hallvard; Øyen, Ole; Sanders, Jan Stephan; Sundar, Sankaran; Bemelman, Frederike J; Sommerer, Claudia; Pascual, Julio; Avihingsanon, Yingyos; Pongskul, Cholatip; Oppenheimer, Frederic; Toselli, Lorenzo; Russ, Graeme; Wang, Zailong; Lopez, Patricia; Kochuparampil, Jossy; Cruzado, Josep M; van der Giet, Markus

    In a 24-month, multicenter, open-label, randomized trial, 715 de novo kidney transplant recipients were randomized at 10-14 weeks to convert to everolimus (n=359) or remain on standard calcineurin inhibitor (CNI) therapy (n=356; 231 tacrolimus; 125 cyclosporine), all with mycophenolic acid and

  3. Efficacy and safety of de-escalation therapy to ertapenem for treatment of infections caused by extended-spectrum-β-lactamase-producing Enterobacteriaceae: an open-label randomized controlled trial.

    Science.gov (United States)

    Rattanaumpawan, Pinyo; Werarak, Peerawong; Jitmuang, Anupop; Kiratisin, Pattarachai; Thamlikitkul, Visanu

    2017-03-01

    Carbapenem antibiotics are considered the treatment of choice for serious extended-spectrum beta-lactamase (ESBL)-producing Gram-negative bacteria (GNB) infections. The study objectives were to evaluate efficacy and safety of de-escalation therapy to ertapenem for treatment of infections caused by extended-spectrum-β-lactamase-producing Enterobacteriaceae. We conducted a randomized controlled trial of adult patients with documented ESBL-producing Enterobacteriaceae infections who had received any group 2 carbapenem for less than 96 h. In the intervention group, the previously-prescribed group 2 carbapenem was de-escalated to ertapenem. In the control group, the group 2 carbapenem was continued. During June 2011-December 2014, 32 patients were randomized to the de-escalation group and 34 to the control group. Most common sites of infection were urinary tract infection (42%). Characteristics of both groups were comparable. By using a 15% predefined margin, ertapenem was non-inferior to control group regarding the clinical cure rate (%Δ = 14.0 [95% confidence interval: -2.4 to 31.1]), the microbiological eradication rate (%Δ = 4.1 [-5.0 to 13.4]), and the superimposed infection rate (%Δ = -16.5 [-38.4 to 5.3]). Patients in the de-escalation group had a significantly lower 28-day mortality rate (9.4% vs. 29.4%; P = .05), a significantly shorter median length of stay (16.5 days [4.0-73.25] vs. 20.0 days [1.0-112.25]; P = .04), and a significantly lower defined daily dose of carbapenem use (12.9 ± 8.9 vs. 18.4 ± 12.6; P = .05). Ertapenem could be safely used as de-escalation therapy for ESBL-producing Enterobacteriaceae infections, once the susceptibility profiles are known. Future studies are needed to investigate ertapenem efficacy against ESBL-producing Enterobacteriaceae pneumonia to determine its applicability in life-threatening conditions. ClinicalTrials.gov identifier: NCT01297842 . Registered on 14 February 2011. First

  4. 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.

  5. Hypoxia marker labeling in tumor biopsies: quantification of labeling variation and criteria for biopsy sectioning

    International Nuclear Information System (INIS)

    Thrall, Donald E.; Rosner, Gary L.; Azuma, Chieko; McEntee, Margaret C.; Raleigh, James A.

    1997-01-01

    Background and purpose: The error associated with using biopsy-based methods for assessing parameters reflective of the tumor microenvironment depends on the variability in distribution of the parameter throughout the tumor and the biopsy sample. Some attention has been given to intratumoral distribution of parameters, but little attention has been given to their intrabiopsy distribution. We evaluated the intrabiopsy distribution of CCI-103F, a 2-nitroimidazole hypoxia marker. Materials and methods: The hypoxia marker CCI-103F was studied in dogs bearing spontaneous solid tumors. Two biopsies were taken from each of seven tumors, for a total of 14 biopsies. Biopsies were serially sectioned and four to six contiguous slides from each 100-150 μm of the biopsy were used to formulate the best estimate of CCI-103F labeled area throughout the biopsy sample. One, two or four slides were then randomly selected from each biopsy and the labeled area, based on this limited sample, was compared to the estimate obtained from counting all available slides. Random sampling of slides was repeated 1000 times for each biopsy sample. Results: CCI-103F labeling variance throughout the biopsy decreased as the estimated overall labeled area in the biopsy decreased. The error associated with estimating the overall labeled area in a biopsy from a randomly selected subset of slides decreased as the number of slides increased, and as the overall labeled area in the biopsy decreased. No minimally labeled biopsy was classified as unlabeled based on limited sampling. Conclusion: With regard to CCI-103F labeling, quantification of the labeled area in four randomly selected slides from a biopsy can provide, in most biopsies, an estimate of the labeled area in the biopsy within an absolute range of ±0.05

  6. Prophylactic perioperative sodium bicarbonate to prevent acute kidney injury following open heart surgery: a multicenter double-blinded randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Michael Haase

    Full Text Available Preliminary evidence suggests a nephroprotective effect of urinary alkalinization in patients at risk of acute kidney injury. In this study, we tested whether prophylactic bicarbonate-based infusion reduces the incidence of acute kidney injury and tubular damage in patients undergoing open heart surgery.In a multicenter, double-blinded (patients, clinical and research personnel, randomized controlled trial we enrolled 350 adult patients undergoing open heart surgery with the use of cardiopulmonary bypass. At induction of anesthesia, patients received either 24 hours of intravenous infusion of sodium bicarbonate (5.1 mmol/kg or sodium chloride (5.1 mmol/kg. The primary endpoint was the proportion of patients developing acute kidney injury. Secondary endpoints included the magnitude of acute tubular damage as measured by urinary neutrophil gelatinase-associated lipocalin (NGAL, initiation of acute renal replacement therapy, and mortality. The study was stopped early under recommendation of the Data Safety and Monitoring Committee because interim analysis suggested likely lack of efficacy and possible harm. Groups were non-significantly different at baseline except that a greater proportion of patients in the sodium bicarbonate group (66/174 [38%] presented with preoperative chronic kidney disease compared to control (44/176 [25%]; p = 0.009. Sodium bicarbonate increased urinary pH (from 6.0 to 7.5, p<0.001. More patients receiving bicarbonate (83/174 [47.7%] developed acute kidney injury compared with control patients (64/176 [36.4%], odds ratio [OR] 1.60 [95% CI 1.04-2.45]; unadjusted p = 0.032. After multivariable adjustment, a non-significant unfavorable group difference affecting patients receiving sodium bicarbonate was found for the primary endpoint (OR 1.45 [0.90-2.33], p = 0.120]. A greater postoperative increase in urinary NGAL in patients receiving bicarbonate infusion was observed compared to control patients (p = 0

  7. The effect of raloxifene on left ventricular hypertrophy in postmenopausal women: A prospective, randomized, and controlled study

    Science.gov (United States)

    Bal, Uğur Abbas; Atar, İlyas; Öktem, Mesut; B. Zeyneloğlu, Hulusi; Yıldırır, Aylin; Kuşcu, Esra; Müderrisoğlu, Haldun

    2015-01-01

    Objective: In healthy women, there is a progressive age-related increase in myocardial mass that is not seen in their male counterparts and occurs primarily in postmenopausal women. Raloxifene is a selective estrogen receptor modulator that has estrogenic actions on bone and the cardiovascular system. The aim of this study was to investigate the effect of raloxifene on myocardial hypertrophy in postmenopausal patients. Methods: A total of 22 postmenopausal osteoporotic women were included in this open-label, randomized, prospective, controlled study. Patients were randomized into two groups: 11 of the patients (group 1) were treated with raloxifene 60 mg/day, and the other 11 patients (group 2) were defined as the control group. Quantitative 2-dimensional and M-mode echocardiographic examination was performed in all patients at the beginning and repeated at the end of the 6-month follow-up period. Left ventricle mass (LVM) and left ventricle mass index (LVMI) were calculated for all patients. Results: The mean age of the patients was 57.2±3.9 years, and baseline clinical characteristics and echocardiographic parameters were similar between the two groups. After 6 months of raloxifene treatment, there was no difference in echocardiographic parameters of LVM and LVMI compared with the control group (201.2±25.9 gr vs. 169.7±46.2 gr, p=0.14 and 120.4±25.9 gr/m2 vs. 105.5±26.3 gr/m2, p=0.195, respectively). There was also no significant difference in LVM and LVMI in the within-group analysis of both groups. Conclusion: Raloxifene therapy does not affect myocardial hypertrophy in postmenopausal women after 6 months of treatment. PMID:25430415

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

    Science.gov (United States)

    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

  9. Nasal Jet-CPAP (variable flow) versus Bubble-CPAP in preterm infants with respiratory distress: an open label, randomized controlled trial.

    Science.gov (United States)

    Bhatti, A; Khan, J; Murki, S; Sundaram, V; Saini, S S; Kumar, P

    2015-11-01

    To compare the failure rates between Jet continuous positive airway pressure device (J-CPAP-variable flow) and Bubble continuous positive airway device (B-CPAP) in preterm infants with respiratory distress. Preterm newborns CPAP (a variable flow device) or B-CPAP (continuous flow device). A standardized protocol was followed for titration, weaning and removal of CPAP. Pressure was monitored close to the nares in both the devices every 6 hours and settings were adjusted to provide desired CPAP. The primary outcome was CPAP failure rate within 72 h of life. Secondary outcomes were CPAP failure within 7 days of life, need for surfactant post-randomization, time to CPAP failure, duration of CPAP and complications of prematurity. An intention to treat analysis was done. One-hundred seventy neonates were randomized, 80 to J-CPAP and 90 to B-CPAP. CPAP failure rates within 72 h were similar in infants who received J-CPAP and in those who received B-CPAP (29 versus 21%; relative risks 1.4 (0.8 to 2.3), P=0.25). Mean (95% confidence intervals) time to CPAP failure was 59 h (54 to 64) in the Jet CPAP group in comparison with 65 h (62 to 68) in the Bubble CPAP group (log rank P=0.19). All other secondary outcomes were similar between the two groups. In preterm infants with respiratory distress starting within 6 h of life, CPAP failure rates were similar with Jet CPAP and Bubble CPAP.

  10. Treatment with silver nitrate versus topical steroid treatment for umbilical granuloma: A non-inferiority randomized control trial.

    Directory of Open Access Journals (Sweden)

    Chikako Ogawa

    Full Text Available The aim of this prospective multicenter randomized controlled trial was to compare the efficacy of silver nitrate cauterization against that of topical steroid ointment in the treatment of neonatal umbilical granuloma.An open-label, non-inferiority randomized controlled trial was conducted from January 2013 to January 2016. The primary endpoint for the silver nitrate cauterization and topical steroid ointment groups was the healing rate after 2 weeks of treatment, applying a non-inferiority margin of 10%. The healing rate was evaluated until completion of 3 weeks of treatment.Participants comprised 207 neonates with newly diagnosed umbilical granuloma, randomized to receive silver nitrate cauterization (n = 104 or topical steroid ointment (n = 103. Healing rates after 2 weeks of treatment were 87.5% (91/104 in the silver nitrate cauterization and 82% (82/100 in the topical steroid ointment group group. The difference between groups was -5.5% (95% confidence interval, -19.1%, 8.4%, indicating that the non-inferiority criterion was not met. After 3 weeks of treatment, the healing rate with topical steroid ointment treatment was almost identical to that of silver nitrate cauterization (94/104 [90.4%] vs. 91/100 [91.0%]; 0.6% [-13.2 to 14.3]. No major complications occurred in either group.This study did not establish non-inferiority of topical steroid ointment treatment relative to silver nitrate cauterization, presumably due to lower healing rates than expected leading to an underpowered trial. However, considering that silver nitrate cauterization carries a distinct risk of chemical burns and that the overall efficacy of topical steroid ointment treatment is similar to that of silver nitrate cauterization, topical steroid ointment might be considered as a good alternative in the treatment of neonatal umbilical granuloma due to its safety and simplicity. To clarify non-inferiority, a larger study is needed.

  11. Efficacy of Acupuncture versus Combined Oral Contraceptive Pill in Treatment of Moderate-to-Severe Dysmenorrhea: A Randomized Controlled Trial

    Science.gov (United States)

    Sriprasert, Intira; Suerungruang, Suparerk; Athilarp, Porntip; Matanasarawoot, Anuchart

    2015-01-01

    This open-label randomized controlled trial was designed to compare the efficacy of acupuncture and combined oral contraceptive (COC) pill in treating moderate-to-severe primary dysmenorrhea. Fifty-two participants were randomly assigned to receive either acupuncture (n = 27) or COC (n = 25) for three menstrual cycles. Mefenamic acid was prescribed as a recue analgesic drug with both groups. The statistical approach used for efficacy and safety assessments was intention-to-treat analysis. By the end of the study, both treatments had resulted in significant improvement over baselines in all outcomes, that is, maximal dysmenorrhea pain scores, days suffering from dysmenorrhea, amount of rescue analgesic used, and quality of life assessed by SF-36 questionnaire. Over the three treatment cycles, COC caused greater reduction in maximal pain scores than acupuncture, while improvements in the remaining outcomes were comparable. Responders were defined as participants whose maximal dysmenorrhea pain scores decreased at least 33% below their baseline. Response rates following both interventions at the end of the study were not statistically different. Acupuncture commonly caused minimal local side effects but did not cause any hormone-related side effects as did COC. In conclusion, acupuncture is an alternative option for relieving dysmenorrhea, especially when COC is not a favorable choice. PMID:26346199

  12. 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

  13. Effectiveness of electroacupuncture for polycystic ovary syndrome: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Chen, Jiao; Feng, Shuwei; Zeng, Jiuzhi; Wu, Xi; Yang, Mingxiao; Tang, Hongzhi; Fan, Huaying; Yang, Jie; Liang, Fanrong

    2016-05-21

    Whether electroacupuncture is effective for patients with polycystic ovary syndrome is still inconclusive. Therefore, this study aims to evaluate the add-on effects of electroacupuncture to conventional drugs for the treatment of polycystic ovary syndrome. This study is a two-center, open-labeled, randomized, controlled trial. A total of 116 eligible patients with polycystic ovary syndrome will be randomly allocated in a 1:1 ratio to the electroacupuncture plus clomiphene citrate group or to the clomiphene citrate group. Participants in the electroacupuncture plus clomiphene citrate group will receive electroacupuncture treatment in addition to clomiphene citrate capsules, whereas participants in the clomiphene citrate group will be prescribed clomiphene citrate capsules only. Electroacupuncture treatment will be performed from the fifth day of menstruation or withdrawal bleeding until the next menstruation, in three sessions per week for three menstrual cycles. The primary outcome is the ovulation rate. The secondary outcomes include the dominant follicle rate, mean number of dominant follicles, endometrial thickness, time point of ovulation, follicular size before ovulation, luteinizing hormone, estradiol level, and pregnancy rate. The measuring points for outcomes will be baseline and the completion of treatment. Any adverse events occurring during the trial process will be recorded. In addition, a quality-monitoring group independent from the research team will be set up to control the quality of the trial. The design and methodological rigor of this trial will allow for the collection of valuable data to evaluate the effectiveness of electroacupuncture for treating polycystic ovary syndrome. Therefore, this trial will contribute reliable evidence for use in clinical decision-making in acupuncture therapy of polycystic ovary syndrome as well as to future research in acupuncture for polycystic ovary syndrome. Chinese Clinical Trial Registry, ChiCTR-IOR-15007358

  14. Brief Report: An Open-Label Study of the Neurosteroid Pregnenolone in Adults with Autism Spectrum Disorder

    Science.gov (United States)

    Fung, Lawrence K.; Libove, Robin A.; Phillips, Jennifer; Haddad, Francois; Hardan, Antonio Y.

    2014-01-01

    The objective of this study was to assess the tolerability and efficacy of pregnenolone in reducing irritability in adults with autism spectrum disorder (ASD). This was a pilot, open-label, 12-week trial that included twelve subjects with a mean age of 22.5 ± 5.8 years. Two participants dropped out of the study due to reasons unrelated to adverse…

  15. An Open-Label Trial of Memantine for Cognitive Impairment in Patients with Posttraumatic Stress Disorder

    Directory of Open Access Journals (Sweden)

    Sriram Ramaswamy

    2015-01-01

    Full Text Available Background. Studies using standard neuropsychological instruments have demonstrated memory deficits in patients with PTSD. We evaluated the efficacy and safety of the N-methyl-D-aspartate antagonist memantine in veterans with PTSD and cognitive impairment. Methods. Twenty-six veterans with PTSD and cognitive impairment received 16 weeks of memantine in an open-label fashion. Cognition was assessed using the Spatial Span, Logical Memory I, and Letter-Number Sequencing subtests of the Wechsler Memory Scale III and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS. RBANS measures attention, language, visuospatial skills, and immediate and delayed memories. The Clinician Administered PTSD Scale (CAPS, Hamilton Depression Scale (HAM-D, Hamilton Anxiety Scale (HAM-A, Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q, and Sheehan Disability Scale (SDS were secondary outcome measures. Results. There was a significant improvement in RBANS, both total and subscale scores (P<0.05, over time. There was a reduction in total CAPS scores, avoidance/numbing symptoms (CAPS-C and hyperarousal symptoms (CAPS-D, HAM-D, Q-LES-Q, and SDS scores. However, there was no reduction in reexperiencing (CAPS-B and HAM-A scores. Memantine was well tolerated. Conclusions. Memantine improved cognitive symptoms, PTSD symptoms, and mood in veterans with PTSD. Randomized double-blind studies are needed to validate these preliminary observations.

  16. Limited Effect of Rebamipide in Addition to Proton Pump Inhibitor (PPI) in the Treatment of Post-Endoscopic Submucosal Dissection Gastric Ulcers: A Randomized Controlled Trial Comparing PPI Plus Rebamipide Combination Therapy with PPI Monotherapy

    OpenAIRE

    Nakamura, Kazuhiko; Ihara, Eikichi; Akiho, Hirotada; Akahoshi, Kazuya; Harada, Naohiko; Ochiai, Toshiaki; Nakamura, Norimoto; Ogino, Haruei; Iwasa, Tsutomu; Aso, Akira; Iboshi, Yoichiro; Takayanagi, Ryoichi

    2016-01-01

    Background/Aims The ability of endoscopic submucosal dissection (ESD) to resect large early gastric cancers (EGCs) results in the need to treat large artificial gastric ulcers. This study assessed whether the combination therapy of rebamipide plus a proton pump inhibitor (PPI) offered benefits over PPI monotherapy. Methods In this prospective, randomized, multicenter, open-label, and comparative study, patients who had undergone ESD for EGC or gastric adenoma were randomized into groups recei...

  17. Quality control of 99mTc-labeled dextran for lymphoscintigraphy

    International Nuclear Information System (INIS)

    Yang, K.A.; Chen Yujeng; Yang Lihwei; Jong Shiangbin; Wu Chungchieng; Chen Jingyeh

    1989-01-01

    99m Tc-labeled dextran has been suggested as a lymphoscintigraphic agent. However, quality-control results from previous studies have been controversial. In this study, the optimal concentration of stannous ion and pH value were determined to obtain maximal labeling. Paper and thin-layer chromatography showed total labeling efficiency as high as 98.4%. Anthrone test of the supernatant of the segments from thin-layer chromatographic strip was performed. Colorimetric determinations verified that dextran was found in the same locations as the peak radioactivity. (orig.)

  18. 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

  19. Preventive nebulization of mucolytic agents and bronchodilating drugs in invasively ventilated intensive care unit patients (NEBULAE): study protocol for a randomized controlled trial.

    Science.gov (United States)

    van der Hoeven, Sophia M; Binnekade, Jan M; de Borgie, Corianne A J M; Bosch, Frank H; Endeman, Henrik; Horn, Janneke; Juffermans, Nicole P; van der Meer, Nardo J M; Merkus, Maruschka P; Moeniralam, Hazra S; van Silfhout, Bart; Slabbekoorn, Mathilde; Stilma, Willemke; Wijnhoven, Jan Willem; Schultz, Marcus J; Paulus, Frederique

    2015-09-02

    Preventive nebulization of mucolytic agents and bronchodilating drugs is a strategy aimed at the prevention of sputum plugging, and therefore atelectasis and pneumonia, in intubated and ventilated intensive care unit (ICU) patients. The present trial aims to compare a strategy using the preventive nebulization of acetylcysteine and salbutamol with nebulization on indication in intubated and ventilated ICU patients. The preventive nebulization of mucolytic agents and bronchodilating drugs in invasively ventilated intensive care unit patients (NEBULAE) trial is a national multicenter open-label, two-armed, randomized controlled non-inferiority trial in the Netherlands. Nine hundred and fifty intubated and ventilated ICU patients with an anticipated duration of invasive ventilation of more than 24 hours will be randomly assigned to receive either a strategy consisting of preventive nebulization of acetylcysteine and salbutamol or a strategy consisting of nebulization of acetylcysteine and/or salbutamol on indication. The primary endpoint is the number of ventilator-free days and surviving on day 28. Secondary endpoints include ICU and hospital length of stay, ICU and hospital mortality, the occurrence of predefined pulmonary complications (acute respiratory distress syndrome, pneumonia, large atelectasis and pneumothorax), and the occurrence of predefined side effects of the intervention. Related healthcare costs will be estimated in a cost-benefit and budget-impact analysis. The NEBULAE trial is the first randomized controlled trial powered to investigate whether preventive nebulization of acetylcysteine and salbutamol shortens the duration of ventilation in critically ill patients. NCT02159196, registered on 6 June 2014.

  20. Detection of Myoglobin with an Open-Cavity-Based Label-Free Photonic Crystal Biosensor.

    Science.gov (United States)

    Zhang, Bailin; Tamez-Vela, Juan Manuel; Solis, Steven; Bustamante, Gilbert; Peterson, Ralph; Rahman, Shafiqur; Morales, Andres; Tang, Liang; Ye, Jing Yong

    2013-01-01

    The label-free detection of one of the cardiac biomarkers, myoglobin, using a photonic-crystal-based biosensor in a total-internal-reflection configuration (PC-TIR) is presented in this paper. The PC-TIR sensor possesses a unique open optical microcavity that allows for several key advantages in biomolecular assays. In contrast to a conventional closed microcavity, the open configuration allows easy functionalization of the sensing surface for rapid biomolecular binding assays. Moreover, the properties of PC structures make it easy to be designed and engineered for operating at any optical wavelength. Through fine design of the photonic crystal structure, biochemical modification of the sensor surface, and integration with a microfluidic system, we have demonstrated that the detection sensitivity of the sensor for myoglobin has reached the clinically significant concentration range, enabling potential usage of this biosensor for diagnosis of acute myocardial infarction. The real-time response of the sensor to the myoglobin binding may potentially provide point-of-care monitoring of patients and treatment effects.

  1. 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

  2. Ipsilateral transversus abdominis plane block provides effective analgesia after appendectomy in children: a randomized controlled trial.

    LENUS (Irish Health Repository)

    Carney, John

    2010-10-01

    The transversus abdominis plane (TAP) block provides effective postoperative analgesia in adults undergoing major abdominal surgery. Its efficacy in children remains unclear, with no randomized clinical trials in this population. In this study, we evaluated its analgesic efficacy over the first 48 postoperative hours after appendectomy performed through an open abdominal incision, in a randomized, controlled, double-blind clinical trial.

  3. Sunbed radiation provokes cutaneous vitamin D synthesis in humans--a randomized controlled trial

    DEFF Research Database (Denmark)

    Thieden, Elisabeth; Jørgensen, Henrik L; Jørgensen, Niklas Rye

    2008-01-01

    We wanted to investigate whether the use of sunbeds with sunlamps emitting mainly UVA and only 0.5% or 1.4% UVB will increase the level of serum 25-hydroxyvitamin D (25(OH)D). In a randomized, controlled, open study on healthy, Caucasian females (> 50 years) sunbed radiation was given as follows...

  4. Examination of the evidence for off-label use of gabapentin.

    Science.gov (United States)

    Mack, Alicia

    2003-01-01

    (1) Describe the relevance of off-label use of gabapentin to managed care pharmacy; (2) summarize recent FDA warnings and media reports related to off-label gabapentin use; (3) review medical information pertaining to the off-label use of gabapentin; (4) outline alternatives to off-label use of gabapentin in an evidence-based fashion, where literature exists to support such alternatives; and (5) encourage key clinicians and decision makers in managed care pharmacy to develop and support programs that restrict the use of gabapentin to specific evidence-based situations. Gabapentin is approved by the U.S. Food and Drug Administration (FDA) for adjunctive therapy in treatment of partial seizures and postherpetic neuralgia. Various off-label (unapproved) uses have been reported, and the use of gabapentin for off-label purposes has reportedly exceeded use for FDAapproved indications. Pharmaceutical marketing practices and physician dissatisfaction with currently available pharmacological treatment options may be key factors that contribute to this prescribing trend. Recently, the media has focused on these issues, noting that many cases of reported safety and effectiveness of gabapentin for off-label use may have been fabricated. A thorough review of the medical and pharmacy literature related to off-label use of gabapentin was performed, and a summary of the literature for the following conditions is presented: bipolar disorder, peripheral neuropathy, diabetic neuropathy, complex regional pain syndrome, attention deficit disorder, restless legs syndrome, trigeminal neuralgia, periodic limb movement disorder of sleep, migraine headaches, and alcohol withdrawal syndrome. A common theme in the medical literature for gabapentin is the prevalence of open-label studies and a lack of randomized controlled clinical trials for all but a small number of indications. In the majority of circumstances where it has reported potential for.off-label. use, gabapentin is not the optimal

  5. 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).

  6. Advantages with prophylactic PEG-rhG-CSF versus rhG-CSF in breast cancer patients receiving multiple cycles of myelosuppressive chemotherapy: an open-label, randomized, multicenter phase III study.

    Science.gov (United States)

    Xie, Jie; Cao, Jun; Wang, Jing-Fen; Zhang, Bai-Hong; Zeng, Xiao-Hua; Zheng, Hong; Zhang, Yang; Cai, Li; Wu, Yu-Dong; Yao, Qiang; Zhao, Xiao-Chun; Mao, Wei-Dong; Jiang, Ai-Mei; Chen, Shao-Shui; Yang, Shun-E; Wang, Shu-Sen; Wang, Jian-Hong; Pan, Yue-Yin; Ren, Bi-Yong; Chen, Yan-Ju; Ouyang, Li-Zhi; Lei, Kai-Jian; Gao, Jing-Hua; Huang, Wen-He; Huang, Zhan; Shou, Tao; He, Yan-Ling; Cheng, Jing; Sun, Yang; Li, Wei-Ming; Cui, Shu-de; Wang, Xin; Rao, Zhi-Guo; Ma, Hu; Liu, Wei; Wu, Xue-Yong; Shen, Wei-Xi; Cao, Fei-Lin; Xiao, Ze-Min; Wu, Biao; Tian, Shu-Yan; Meng, Dong; Shen, Peng; Wang, Bi-Yun; Wang, Zhonghua; Zhang, Jian; Wang, Leiping; Hu, Xi-Chun

    2018-04-01

    PEG-rhG-CSF reduces neutropenia and improves chemotherapy safety. In China's registration trial (CFDA: 2006L01305), we assessed its efficacy and safety against rhG-CSF, and prospectively explored its value over multiple cycles of chemotherapy. In this open-label, randomized, multicenter phase 3 study, breast cancer patients (n = 569) were randomized to receive PEG-rhG-CSF 100 µg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 µg/kg/d after chemotherapy. The primary endpoints were the incidence and duration of grade 3/4 neutropenia during cycle 1. Secondary endpoints included the incidence and duration of grade 3/4 neutropenia during cycles 2-4, the incidence of febrile neutropenia, and the safety. A once-per-cycle PEG-rhG-CSF at either 100 µg/kg or 6 mg was not different from daily injections of rhG-CSF for either incidence or duration of grade 3/4 neutropenia. Interestingly, a substantial difference was noted during cycle 2, and the difference became bigger over cycles 3-4, reaching a statistical significance at cycle 4 in either incidence (P = 0.0309) or duration (P = 0.0289) favoring PEG-rhG-CSF. A significant trend toward a lower incidence of all-grade adverse events was noted at 129 (68.98%), 142 (75.53%), and 160 (82.47%) in the PEG-rhG-CSF 100 µg/kg and 6 mg and rhG-CSF groups, respectively (P = 0.0085). The corresponding incidence of grade 3/4 drug-related adverse events was 2/187 (1.07%), 1/188 (0.53%), and 8/194 (4.12%), respectively (P = 0.0477). Additionally, PFS in metastatic patients preferred PEG-rhG-CSF to rhG-CSF despite no significance observed by Kaplan-Meier analysis (n = 49, P = 0.153). PEG-rhG-CSF is a more convenient and safe formulation and a more effective prophylactic measure in breast cancer patients receiving multiple cycles of chemotherapy.

  7. Colorectal cancer (CRC) monitoring by 6-monthly 18FDG-PET/CT: an open-label multicentre randomised trial.

    Science.gov (United States)

    Sobhani, I; Itti, E; Luciani, A; Baumgaertner, I; Layese, R; André, T; Ducreux, M; Gornet, J-M; Goujon, G; Aparicio, T; Taieb, J; Bachet, J-B; Hemery, F; Retbi, A; Mons, M; Flicoteaux, R; Rhein, B; Baron, S; Cherrak, I; Rufat, P; Le Corvoisier, P; de'Angelis, N; Natella, P-A; Maoulida, H; Tournigand, C; Durand Zaleski, I; Bastuji-Garin, S

    2018-04-01

    [18F]2-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (18FDG-PET/CT) has high sensitivity for detecting recurrences of colorectal cancer (CRC). Our objective was to determine whether adding routine 6-monthly 18FDG-PET/CT to our usual monitoring strategy improved patient outcomes and to assess the effect on costs. In this open-label multicentre trial, patients in remission of CRC (stage II perforated, stage III, or stage IV) after curative surgery were randomly assigned (1 : 1) to usual monitoring alone (3-monthly physical and tumour marker assays, 6-monthly liver ultrasound and chest radiograph, and 6-monthly whole-body computed tomography) or with 6-monthly 18FDG-PET/CT, for 3 years. A multidisciplinary committee reviewed each patient's data every 3 months and classified the recurrence status as yes/no/doubtful. Recurrences were treated with curative surgery alone if feasible and with chemotherapy otherwise. The primary end point was treatment failure defined as unresectable recurrence or death. Relative risks were estimated, and survival was analysed using the Kaplan-Meier method, log-rank test, and Cox models. Direct costs were compared. Of the 239 enrolled patients, 120 were in the intervention arm and 119 in the control arm. The failure rate was 29.2% (31 unresectable recurrences and 4 deaths) in the intervention group and 23.7% (27 unresectable recurrences and 1 death) in the control group (relative risk = 1.23; 95% confidence interval, 0.80-1.88; P = 0.34). The multivariate analysis also showed no significant difference (hazards ratio, 1.33; 95% confidence interval, 0.8-2.19; P = 0.27). Median time to diagnosis of unresectable recurrence (months) was significantly shorter in the intervention group [7 (3-20) versus 14.3 (7.3-27), P = 0.016]. Mean cost/patient was higher in the intervention group (18 192 ± 27 679 € versus 11 131 ± 13  €, P CRC. The control group had very close follow

  8. The efficacy of gum chewing in reducing postoperative ileus: a multisite randomized controlled trial.

    Science.gov (United States)

    Forrester, David Anthony Tony; Doyle-Munoz, Janet; McTigue, Toni; D'Andrea, Stephanie; Natale-Ryan, Angela

    2014-01-01

    The purpose of this prospective, attention-controlled, randomized study was to determine whether postoperative gum chewing reduces the duration of postoperative ileus symptoms following elective open or laparoscopic sigmoid colectomy when compared with standard care or an attention-control intervention. Forty-seven subjects scheduled for either an open or laparoscopic colon resection participated in the study. Subjects were recruited preoperatively at the preadmission learning centers of the 2 acute care medical centers that comprised the study settings. Subjects were randomized to 3 groups: (1) standard postoperative care (n = 18); (2) standard care and a silicone-adhesive patch applied to the deltoid region of the upper arm as an attention control (n = 16); and (3) standard care and gum chewing (n = 13). Standard postoperative care included removal of the nasogastric tube, early ambulation, nothing by mouth with ice chips only until the first passage of flatus, and then advancement of diet until tolerance of solid food. No statistically significant differences were found among the 3 study groups for the 4 postoperative outcome variables measured: (1) first passage of flatus; (2) first bowel movement; (3) return of hunger; and (4) ability to tolerate solid food for one meal. Postoperative gum chewing was not found to be more effective than standard postoperative care or our attention-control intervention in reducing the duration of postoperative ileus symptoms, length of stay, or complications among patients following open/laparoscopic sigmoid colectomy.

  9. 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...

  10. 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.

  11. 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.

  12. Clinical applications of cells labelling

    International Nuclear Information System (INIS)

    Gonzalez, B.M.

    1994-01-01

    Blood cells labelled with radionuclides are reviewed and main applications are described. Red blood cell labelling by both random and specific principle. A table with most important clinical uses, 99mTc labelling of RBC are described pre tinning and in vivo reduction of Tc, in vitro labelling and administration of labelled RBC and in vivo modified technique. Labelled leucocytes with several 99mTc-complex radiopharmaceuticals by in vitro technique and specific monoclonal s for white cells(neutrofiles). Labelled platelets for clinical use and research by in vitro technique and in vivo labelling

  13. Treatment of clozapine-associated obesity and diabetes with exenatide in adults with schizophrenia: A randomized controlled trial (CODEX).

    Science.gov (United States)

    Siskind, Dan J; Russell, Anthony W; Gamble, Clare; Winckel, Karl; Mayfield, Karla; Hollingworth, Sam; Hickman, Ingrid; Siskind, Victor; Kisely, Steve

    2018-04-01

    Clozapine causes obesity and type 2 diabetes (T2DM). Glucagon-like peptide-1 (GLP-1) receptor agonists (e.g. exenatide) can counter clozapine-associated GLP-1 dysregulation in animals, and may be beneficial in people on clozapine. This randomized, controlled, open-label, pilot trial evaluated weekly exenatide for weight loss among clozapine-treated obese adults with schizophrenia, with or without T2DM. A total of 28 outpatients were randomized to once-weekly extended-release subcutaneous exenatide or usual care for 24 weeks. The primary outcome was proportion of participants with >5% weight loss. All 28 participants completed the study; 3/14 in the exenatide group and 2/14 in the usual care group had T2DM. Six people on exenatide achieved >5% weight loss vs one receiving usual care (P = .029). Compared with usual care, participants on exenatide had greater mean weight loss (-5.29 vs -1.12 kg; P = .015) and body mass index reduction (-1.78 vs -0.39 kg/m 2 ; P = .019), and reduced fasting glucose (-0.34 vs 0.39 mmol/L; P = .036) and glycated haemoglobin levels (-0.21% vs 0.03%; P = .004). There were no significant differences in other metabolic syndrome components. Exenatide may be a promising therapeutic agent for glycaemic control and weight loss in clozapine-treated people with obesity, and could assist in reducing clozapine-associated cardio-metabolic morbidity and mortality. © 2017 John Wiley & Sons Ltd.

  14. Adjuvant capecitabine plus bevacizumab versus capecitabine alone in patients with colorectal cancer (QUASAR 2): an open-label, randomised phase 3 trial.

    Science.gov (United States)

    Kerr, Rachel S; Love, Sharon; Segelov, Eva; Johnstone, Elaine; Falcon, Beverly; Hewett, Peter; Weaver, Andrew; Church, David; Scudder, Claire; Pearson, Sarah; Julier, Patrick; Pezzella, Francesco; Tomlinson, Ian; Domingo, Enric; Kerr, David J

    2016-11-01

    Antiangiogenic agents have established efficacy in the treatment of metastatic colorectal cancer. We investigated whether bevacizumab could improve disease-free survival in the adjuvant setting after resection of the primary tumour. For the open-label, randomised, controlled QUASAR 2 trial, which was done at 170 hospitals in seven countries, we recruited patients aged 18 years or older with WHO performance status scores of 0 or 1 who had undergone potentially curative surgery for histologically proven stage III or high-risk stage II colorectal cancer. Patients were randomly assigned (1:1) to receive eight 3-week cycles of oral capecitabine alone (1250 mg/m 2 twice daily for 14 days followed by a break for 7 days) or the same regimen of oral capecitabine plus 16 cycles of 7·5 mg/kg bevacizumab by intravenous infusion over 90 min on day 1 of each cycle. Randomisation was done by a computer-generated schedule with use of minimisation with a random element stratified by age, disease stage, tumour site, and country. The study was open label and no-one was masked to treatment assignment. The primary endpoint was 3-year disease-free survival, assessed in the intention-to-treat population. Toxic effects were assessed in patients who received at least one dose of randomised treatment. This trial is registered with the ISRCTN registry, number ISRCTN45133151. Between April 25, 2005, and Oct 12, 2010, 1952 eligible patients were enrolled, of whom 1941 had assessable data (968 in the capecitabine alone group and 973 in the capecitabine and bevacizumab group). Median follow-up was 4·92 years (IQR 4·00-5·16). Disease-free survival at 3 years did not differ between the groups (75·4%, 95% CI 72·5-78·0 in the capecitabine and bevacizumab group vs 78·4%, 75·7-80·9 in the capecitabine alone group; hazard ratio 1·06, 95% CI 0·89-1·25, p=0·54). The most common grade 3-4 adverse events were hand-foot syndrome (201 [21%] of 963 in the capecitabine alone group vs 257 [27%] of

  15. A platform for dynamic simulation and control of movement based on OpenSim and MATLAB.

    Science.gov (United States)

    Mansouri, Misagh; Reinbolt, Jeffrey A

    2012-05-11

    Numerical simulations play an important role in solving complex engineering problems and have the potential to revolutionize medical decision making and treatment strategies. In this paper, we combine the rapid model-based design, control systems and powerful numerical method strengths of MATLAB/Simulink with the simulation and human movement dynamics strengths of OpenSim by developing a new interface between the two software tools. OpenSim is integrated with Simulink using the MATLAB S-function mechanism, and the interface is demonstrated using both open-loop and closed-loop control systems. While the open-loop system uses MATLAB/Simulink to separately reproduce the OpenSim Forward Dynamics Tool, the closed-loop system adds the unique feature of feedback control to OpenSim, which is necessary for most human movement simulations. An arm model example was successfully used in both open-loop and closed-loop cases. For the open-loop case, the simulation reproduced results from the OpenSim Forward Dynamics Tool with root mean square (RMS) differences of 0.03° for the shoulder elevation angle and 0.06° for the elbow flexion angle. MATLAB's variable step-size integrator reduced the time required to generate the forward dynamic simulation from 7.1s (OpenSim) to 2.9s (MATLAB). For the closed-loop case, a proportional-integral-derivative controller was used to successfully balance a pole on model's hand despite random force disturbances on the pole. The new interface presented here not only integrates the OpenSim and MATLAB/Simulink software tools, but also will allow neuroscientists, physiologists, biomechanists, and physical therapists to adapt and generate new solutions as treatments for musculoskeletal conditions. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Does flushing the endometrial cavity with follicular fluid after oocyte retrieval affect pregnancy rates in subfertile women undergoing intracytoplasmic sperm injection? A randomized controlled trial.

    Science.gov (United States)

    Hashish, N M; Badway, H S; Abdelmoty, H I; Mowafy, A; Youssef, M A F M

    2014-05-01

    Follicular fluid of mature oocytes is rich in growth factors and cytokines that may exert paracrine and autocrine effects on implantation. The aim of this study was to investigate if flushing the endometrial cavity with follicular fluid after oocyte retrieval improved pregnancy rates in subfertile women undergoing intracytoplasmic sperm injection (ICSI). One hundred subfertile women undergoing ICSI between April 2012 and September 2012 at the centre for reproductive medicine, Cairo University, Egypt were enrolled in this open label, parallel randomized controlled study. Patients were randomized into two groups at the start of treatment using a computer-generated programme and sealed opaque envelopes: the follicular fluid group (n=50) and the control group (n=50). Inclusion criteria were: age 20-38 years; basal follicle-stimulating hormone 1000pg/ml and failure in previous in-vitro fertilization/ICSI cycles; and severe male factor infertility. Clinical pregnancy and implantation rates were higher in the follicular fluid group compared with the control group [354% (17/48) vs 319% (15/47); p=0718] and (18.6% vs 11.3%; p=0.153), respectively. However, the difference was not statistically significant. Flushing the endometrial cavity with follicular fluid after oocyte retrieval neither improved nor adversely affected clinical pregnancy and implantation rates in subfertile women undergoing ICSI. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  17. 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.

  18. Simplification to abacavir/lamivudine + atazanavir maintains viral suppression and improves bone and renal biomarkers in ASSURE, a randomized, open label, non-inferiority trial.

    Directory of Open Access Journals (Sweden)

    David A Wohl

    Full Text Available Simplification of antiretroviral therapy in patients with suppressed viremia may minimize long-term adverse effects. The study's primary objective was to determine whether abacavir/lamivudine + atazanavir (ABC/3TC+ATV was virologically non-inferior to tenofovir/emtricitabine + atazanavir/ritonavir (TDF/FTC+ATV/r over 24 weeks in a population of virologically suppressed, HIV-1 infected patients.This open-label, multicenter, non-inferiority study enrolled antiretroviral experienced, HIV-infected adults currently receiving a regimen of TDF/FTC+ATV/r for ≥ 6 months with no history of virologic failure and whose HIV-1 RNA had been ≤ 75 copies/mL on 2 consecutive measurements including screening. Patients were randomized 1 ∶ 2 to continue current treatment or simplify to ABC/3TC+ATV.The primary endpoint was the proportion of patients with HIV-RNA<50 copies/mL at Week 24 by the Time to Loss of Virologic Response (TLOVR algorithm. Secondary endpoints included alternative measures of efficacy, adverse events (AEs, and fasting lipids. Exploratory endpoints included inflammatory, coagulation, bone, and renal biomarkers.After 24 weeks, ABC/3TC+ATV (n = 199 was non-inferior to TDF/FTC+ATV/r (n = 97 by both the primary analysis (87% in both groups and all secondary efficacy analyses. Rates of grade 2-4 AEs were similar between the two groups (40% vs 37%, respectively, but an excess of hyperbilirubinemia made the rate of grade 3-4 laboratory abnormalities higher in the TDF/FTC+ATV/r group (30% compared with the ABC/3TC+ATV group (13%. Lipid levels were stable except for HDL cholesterol, which increased significantly in the ABC/3TC+ATV group. Bone and renal biomarkers improved significantly between baseline and Week 24 in patients taking ABC/3TC+ATV, and the difference between groups was significant at Week 24. No significant changes occurred in any inflammatory or coagulation biomarker within or between treatment groups.After 24 weeks, simplification to

  19. Affect labeling enhances exposure effectiveness for public speaking anxiety.

    Science.gov (United States)

    Niles, Andrea N; Craske, Michelle G; Lieberman, Matthew D; Hur, Christopher

    2015-05-01

    Exposure is an effective treatment for anxiety but many patients do not respond fully. Affect labeling (labeling emotional experience) attenuates emotional responding. The current project examined whether affect labeling enhances exposure effectiveness in participants with public speaking anxiety. Participants were randomized to exposure with or without affect labeling. Physiological arousal and self-reported fear were assessed before and after exposure and compared between groups. Consistent with hypotheses, participants assigned to Affect Labeling, especially those who used more labels during exposure, showed greater reduction in physiological activation than Control participants. No effect was found for self-report measures. Also, greater emotion regulation deficits at baseline predicted more benefit in physiological arousal from exposure combined with affect labeling than exposure alone. The current research provides evidence that behavioral strategies that target prefrontal-amygdala circuitry can improve treatment effectiveness for anxiety and these effects are particularly pronounced for patients with the greatest deficits in emotion regulation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Safety of Repeated Open-Label Treatment Courses of Intravenous Ofatumumab, a Human Anti-CD20 Monoclonal Antibody, in Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Quattrocchi, Emilia; Ostergaard, Mikkel; Taylor, Peter C.

    2016-01-01

    Objectives To investigate the safety of ofatumumab retreatment in rheumatoid arthritis. Methods Patients with active rheumatoid arthritis participating in two phase III trials (OFA110635 and OFA110634) and a phase II extension trial (OFA111752) received individualised open-label ofatumumab retrea...

  1. Open core control software for surgical robots.

    Science.gov (United States)

    Arata, Jumpei; Kozuka, Hiroaki; Kim, Hyung Wook; Takesue, Naoyuki; Vladimirov, B; Sakaguchi, Masamichi; Tokuda, Junichi; Hata, Nobuhiko; Chinzei, Kiyoyuki; Fujimoto, Hideo

    2010-05-01

    In these days, patients and doctors in operation room are surrounded by many medical devices as resulting from recent advancement of medical technology. However, these cutting-edge medical devices are working independently and not collaborating with each other, even though the collaborations between these devices such as navigation systems and medical imaging devices are becoming very important for accomplishing complex surgical tasks (such as a tumor removal procedure while checking the tumor location in neurosurgery). On the other hand, several surgical robots have been commercialized, and are becoming common. However, these surgical robots are not open for collaborations with external medical devices in these days. A cutting-edge "intelligent surgical robot" will be possible in collaborating with surgical robots, various kinds of sensors, navigation system and so on. On the other hand, most of the academic software developments for surgical robots are "home-made" in their research institutions and not open to the public. Therefore, open source control software for surgical robots can be beneficial in this field. From these perspectives, we developed Open Core Control software for surgical robots to overcome these challenges. In general, control softwares have hardware dependencies based on actuators, sensors and various kinds of internal devices. Therefore, these control softwares cannot be used on different types of robots without modifications. However, the structure of the Open Core Control software can be reused for various types of robots by abstracting hardware dependent parts. In addition, network connectivity is crucial for collaboration between advanced medical devices. The OpenIGTLink is adopted in Interface class which plays a role to communicate with external medical devices. At the same time, it is essential to maintain the stable operation within the asynchronous data transactions through network. In the Open Core Control software, several

  2. Art therapy and music reminiscence activity in the prevention of cognitive decline: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Mahendran, Rathi; Rawtaer, Iris; Fam, Johnson; Wong, Jonathan; Kumar, Alan Prem; Gandhi, Mihir; Jing, Kenny Xu; Feng, Lei; Kua, Ee Heok

    2017-07-12

    Attention has shifted to the use of non-pharmacological interventions to prevent cognitive decline as a preventive strategy, as well as for those at risk and those with mild cognitive impairment. Early introduction of psycho-social interventions can address cognitive decline and significantly impact quality of life and the wellbeing of elderly individuals. This pilot study explores the feasibility of using art therapy and music reminiscence activity to improve the cognition of community living elderly with mild cognitive impairment. This open-label, interventional study involves a parallel randomized controlled trial design with three arms (two intervention arms and a control group) over a nine-month period. Participants will be community-living elderly individuals aged 60-85 years, both genders, who meet predefined inclusion and exclusion criteria. In the initial three months, interventions will be provided weekly and for the remaining six months fortnightly. A sample size of 90 participants is targeted based on expected neuropsychological test performance, a primary outcome measure, and drop-out rates. The randomization procedure will be carried out via a web-based randomization system. Interventions will be provided by trained staff with a control group not receiving any intervention but continuing life as usual. Assessments will be done at baseline, three months, and nine months, and include neuroimaging to measure cerebral changes and neuropsychological tests to measure for changes in cognition. Secondary outcome measures will include mood changes in anxiety and depression and telomere lengths. Statistical analysis will be undertaken by statisticians; all efficacy analysis will be carried out on an intention-to-treat basis. Primary and secondary outcomes will be modeled using the linear mixed model for repeated measurements and further analysis may be undertaken to adjust for potential confounders. This will be the first study to compare the effectiveness of

  3. 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

  4. Open versus laparoscopic liver resection for colorectal liver metastases (the Oslo-CoMet Study): study protocol for a randomized controlled trial.

    Science.gov (United States)

    Fretland, Åsmund Avdem; Kazaryan, Airazat M; Bjørnbeth, Bjørn Atle; Flatmark, Kjersti; Andersen, Marit Helen; Tønnessen, Tor Inge; Bjørnelv, Gudrun Maria Waaler; Fagerland, Morten Wang; Kristiansen, Ronny; Øyri, Karl; Edwin, Bjørn

    2015-03-04

    Laparoscopic liver resection is used in specialized centers all over the world. However, laparoscopic liver resection has never been compared with open liver resection in a prospective, randomized trial. The Oslo-CoMet Study is a randomized trial into laparoscopic versus open liver resection for the surgical management of hepatic colorectal metastases. The primary outcome is 30-day perioperative morbidity. Secondary outcomes include 5-year survival (overall, disease-free and recurrence-free), resection margins, recurrence pattern, postoperative pain, health-related quality of life, and evaluation of the inflammatory response. A cost-utility analysis of replacing open surgery with laparoscopic surgery will also be performed. The study includes all resections for colorectal liver metastases, except formal hemihepatectomies, resections where reconstruction of vessels/bile ducts is necessary and resections that need to be combined with ablation. All patients will participate in an enhanced recovery after surgery program. A biobank of liver and tumor tissue will be established and molecular analysis will be performed. After 35 months of recruitment, 200 patients have been included in the trial. Molecular and immunology data are being analyzed. Results for primary and secondary outcome measures will be presented following the conclusion of the study (late 2015). The Oslo-CoMet Study will provide the first level 1 evidence on the benefits of laparoscopic liver resection for colorectal liver metastases. The trial was registered in ClinicalTrals.gov (NCT01516710) on 19 January 2012.

  5. Preference towards Control in Risk Taking: Control, No Control, or Randomize?

    OpenAIRE

    Li, King King

    2010-01-01

    This paper experimentally investigates preference towards different methods of control in risk taking. Participants are asked to choose between different ways for choosing which numbers to bet on for a gamble. They can choose the numbers themselves (control), let the experimenter choose (no control), or randomize. It is found that in addition to the more conventional preference for control, some participants prefer not to control, or randomization. These preferences are robust as participants...

  6. 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.

  7. Improved quality control of carbon-14 labelled compounds

    International Nuclear Information System (INIS)

    Leonhardt, J.W.; Fuchs, P.; Standtke, K.

    1997-01-01

    IUT Ltd is a producer of carbon-14 labelled organic compounds like benzene, methanol, phenol, formaldehyde, Na-acetates and also special ordered compounds. The quality control of these compounds is carried out by means of HPLC and GC-MS due to chemical purity. Molar activity was determined by Liquid Scintillation Counting and HPLC being equipped by a radioactivity detector. Unfortunately the accuracy of the activity determination was arrived only ±4% relatively. This error is too high because of the large dilution factors. In respect of the IUT accreditation as an analytical laboratory in Germany the accuracy had to be improved remarkably. Therefore the GC-MS-determination of molar activities of labelled compounds is used as the 14 C-labelled compound. A special evaluation code is used to determine the enrichment values relative to the unlabelled molecules. Taking into account the results of GC-MS the accuracy of molar activity determination is improved to ±2%. The spectra evaluation is demonstrated and some examples are discussed

  8. Deuterium labeled cannabinoids

    International Nuclear Information System (INIS)

    Driessen, R.A.

    1979-01-01

    Complex reactions involving ring opening, ring closure and rearrangements hamper complete understanding of the fragmentation processes in the mass spectrometric fragmentation patterns of cannabinoids. Specifically labelled compounds are very powerful tools for obtaining more insight into fragmentation mechanisms and ion structures and therefore the synthesis of specifically deuterated cannabinoids was undertaken. For this, it was necessary to investigate the preparation of cannabinoids, appropriately functionalized for specific introduction of deuterium atom labels. The results of mass spectrometry with these labelled cannabinoids are described. (Auth.)

  9. Deconstructing tolerance with clobazam: Post hoc analyses from an open-label extension study.

    Science.gov (United States)

    Gidal, Barry E; Wechsler, Robert T; Sankar, Raman; Montouris, Georgia D; White, H Steve; Cloyd, James C; Kane, Mary Clare; Peng, Guangbin; Tworek, David M; Shen, Vivienne; Isojarvi, Jouko

    2016-10-25

    To evaluate potential development of tolerance to adjunctive clobazam in patients with Lennox-Gastaut syndrome. Eligible patients enrolled in open-label extension study OV-1004, which continued until clobazam was commercially available in the United States or for a maximum of 2 years outside the United States. Enrolled patients started at 0.5 mg·kg -1 ·d -1 clobazam, not to exceed 40 mg/d. After 48 hours, dosages could be adjusted up to 2.0 mg·kg -1 ·d -1 (maximum 80 mg/d) on the basis of efficacy and tolerability. Post hoc analyses evaluated mean dosages and drop-seizure rates for the first 2 years of the open-label extension based on responder categories and baseline seizure quartiles in OV-1012. Individual patient listings were reviewed for dosage increases ≥40% and increasing seizure rates. Data from 200 patients were included. For patients free of drop seizures, there was no notable change in dosage over 24 months. For responder groups still exhibiting drop seizures, dosages were increased. Weekly drop-seizure rates for 100% and ≥75% responders demonstrated a consistent response over time. Few patients had a dosage increase ≥40% associated with an increase in seizure rates. Two-year findings suggest that the majority of patients do not develop tolerance to the antiseizure actions of clobazam. Observed dosage increases may reflect best efforts to achieve seizure freedom. It is possible that the clinical development of tolerance to clobazam has been overstated. NCT00518713 and NCT01160770. This study provides Class III evidence that the majority of patients do not develop tolerance to clobazam over 2 years of treatment. © 2016 American Academy of Neurology.

  10. Effect of probiotics on the incidence of ventilator-associated pneumonia in critically ill patients: a randomized controlled multicenter trial.

    Science.gov (United States)

    Zeng, Juan; Wang, Chun-Ting; Zhang, Fu-Shen; Qi, Feng; Wang, Shi-Fu; Ma, Shuang; Wu, Tie-Jun; Tian, Hui; Tian, Zhao-Tao; Zhang, Shu-Liu; Qu, Yan; Liu, Lu-Yi; Li, Yuan-Zhong; Cui, Song; Zhao, He-Ling; Du, Quan-Sheng; Ma, Zhuang; Li, Chun-Hua; Li, Yun; Si, Min; Chu, Yu-Feng; Meng, Mei; Ren, Hong-Sheng; Zhang, Ji-Cheng; Jiang, Jin-Jiao; Ding, Min; Wang, Yu-Ping

    2016-06-01

    To evaluate the potential preventive effect of probiotics on ventilator-associated pneumonia (VAP). This was an open-label, randomized, controlled multicenter trial involving 235 critically ill adult patients who were expected to receive mechanical ventilation for ≥48 h. The patients were randomized to receive (1) a probiotics capsule containing live Bacillus subtilis and Enterococcus faecalis (Medilac-S) 0.5 g three times daily through a nasogastric feeding tube plus standard preventive strategies or (2) standard preventive strategies alone, for a maximum of 14 days. The development of VAP was evaluated daily, and throat swabs and gastric aspirate were cultured at baseline and once or twice weekly thereafter. The incidence of microbiologically confirmed VAP in the probiotics group was significantly lower than that in the control patients (36.4 vs. 50.4 %, respectively; P = 0.031). The mean time to develop VAP was significantly longer in the probiotics group than in the control group (10.4 vs. 7.5 days, respectively; P = 0.022). The proportion of patients with acquisition of gastric colonization of potentially pathogenic microorganisms (PPMOs) was lower in the probiotics group (24 %) than the control group (44 %) (P = 0.004). However, the proportion of patients with eradication PPMO colonization on both sites of the oropharynx and stomach were not significantly different between the two groups. The administration of probiotics did not result in any improvement in the incidence of clinically suspected VAP, antimicrobial consumption, duration of mechanical ventilation, mortality and length of hospital stay. Therapy with the probiotic bacteria B. Subtilis and E. faecalis are an effective and safe means for preventing VAP and the acquisition of PPMO colonization in the stomach.

  11. The effect of physician and patient education when combined with vardenafil treatment in Canadian males with erectile dysfunction: an open-label, factorial-designed, cluster-randomized clinical trial.

    Science.gov (United States)

    Brock, Gerald; Carrier, Serge; Alarie, Pierre; Pommerville, Peter; Casey, Richard; Harris, Stewart; Ward, Richard

    2008-03-01

    Studies evaluating the effect of education on treatment success with phosphodiesterase type 5 (PDE5) inhibitor therapy in men with erectile dysfunction (ED) are limited. Additional education of the primary care physician (PCP) and the patient are thought to optimize the treatment of ED. To assess the impact of education of the PCP or of the patient in the treatment of ED with vardenafil relative to usual care. In this 12-week, open-label, multicenter, factorial-designed, cluster-randomized Canadian study, 1,029 patients with ED were enrolled into four different education groups: usual care, patient education, PCP education, and both PCP and patient education. All groups started on vardenafil 10 mg, with the option to titrate at weeks 4 and 8. The primary efficacy measure was the difference at week 4 last observation carried forward (LOCF) in the overall improvement in erectile function (EF) as measured by the Global Assessment Question (GAQ), while on background vardenafil, between those receiving education vs. those who did not. Other secondary assessments included responses to diary questions regarding penetration (sexual encounter profile, SEP2) and erection maintenance (SEP3), and to questionnaires regarding treatment satisfaction (Erectile Dysfunction Inventory of Treatment Satisfaction [EDITS]). A total of 956 patients were included in the intent-to-treat population. Mean baseline International Index of Erectile Function-EF domain score was 13. GAQ response rates at week 4 LOCF were high (>80%) for all groups, regardless of the education given. Mean per patient SEP2 and SEP3 rates at week 12 LOCF were 86-89% and 79-83%, respectively. In an exploratory analysis, a positive relationship between GAQ responses and EDITS scores was observed (P satisfaction regardless of the education given. The benefits of education for PCP and patients in Canada were possibly masked by a ceiling effect in this study population.

  12. 40 CFR 91.113 - Requirement of certification-emission control information label and engine identification number.

    Science.gov (United States)

    2010-07-01

    ... control information label and engine identification number. 91.113 Section 91.113 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CONTROL OF EMISSIONS FROM... certification—emission control information label and engine identification number. (a) The engine manufacturer...

  13. Effect of Aerobic Training on Peak Oxygen Uptake Among Seniors Aged 70 or Older: A Meta-Analysis of Randomized Controlled Trials.

    Science.gov (United States)

    Bouaziz, Walid; Kanagaratnam, Lukshe; Vogel, Thomas; Schmitt, Elise; Dramé, Moustapha; Kaltenbach, Georges; Geny, Bernard; Lang, Pierre Olivier

    2018-01-02

    Older adults undergo a progressive decline in cardiorespiratory fitness and functional capacity. This lower peak oxygen uptake (VO 2peak ) level is associated with increased risk of frailty, dependency, loss of autonomy, and mortality from all causes. Regular physical activity and particularly aerobic training (AT) have been shown to contribute to better and healthy aging. We conducted a meta-analysis to measure the exact benefit of AT on VO 2peak in seniors aged 70 years or older. A comprehensive, systematic database search for articles was performed in Embase, Medline, PubMed Central, Science Direct, Scopus, and Web of Science using key words. Two reviewers independently assessed interventional studies for potential inclusion. Ten randomized controlled trials (RCTs) were included totaling 348 seniors aged 70 years or older. Across the trials, no high risk of bias was measured and all considered open-label arms for controls. With significant heterogeneity between the RCTs (all p seniors were, respectively, 1.72 (95% CI: 0.34-3.10) and 1.47 (95% CI: 0.60-2.34). This meta-analysis confirms the AT-associated benefits on VO 2peak in healthy and unhealthy seniors.

  14. 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.

    Science.gov (United States)

    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

  15. Phenobarbital versus morphine in the management of neonatal abstinence syndrome, a randomized control trial.

    Science.gov (United States)

    Nayeri, Fatemeh; Sheikh, Mahdi; Kalani, Majid; Niknafs, Pedram; Shariat, Mamak; Dalili, Hosein; Dehpour, Ahmad-Reza

    2015-05-15

    Evaluating the efficacy of the loading and tapering dose of Phenobarbital versus oral Morphine in the management of NAS. This randomized, open-label, controlled trial was conducted on 60 neonates born to illicit drugs dependent mothers at Vali-Asr and Akbar-Abadi hospitals, Tehran, Iran, who exhibited NAS requiring medical therapy. The neonates were randomized to receive either: Oral Morphine Sulfate or a loading dose of Phenobarbital followed by a tapering dose. The duration of treatment required for NAS resolution, the total hospital stay and the requirement for additional second line treatment were compared between the treatment groups. The Mean ± Standard Deviation for the duration of treatment required for the resolution of NAS was 8.5 ± 5 days in the Morphine group and 8.5 ± 4 days in the Phenobarbital group (P = 0.9). The duration of total hospital stay was 12.6 ± 5.6 days in the Morphine group and 12.5 ± 5.3 days in the Phenobarbital group (P = 0.7). 3.3 % in the Morphine group versus 6.6 % in the Phenobarbital group required adjunctive treatment (P = 0.5). There were no significant differences in the duration of treatment, duration of hospital stay, and the requirement for adjunctive treatment, between the neonates with NAS who received Morphine Sulfate and neonates who received a loading and tapering dose of Phenobarbital. This study is registered at the Iranian Registry of Clinical Trials ( www.irct.ir ) which is a Primary Registry in the WHO Registry Network. (Registration Number =  IRCT201406239568N8 ).

  16. Short-term effects of instruction in home heating on indoor temperature and blood pressure in elderly people: a randomized controlled trial.

    Science.gov (United States)

    Saeki, Keigo; Obayashi, Kenji; Kurumatani, Norio

    2015-11-01

    Increased mortality from cardiovascular disease in winter is partly explained by increased blood pressure (BP) caused by cold exposure. For physicians, instruction in home heating is feasible option to reduce cold exposure, but the effectiveness remains unknown. To determine whether instruction in home heating increases indoor temperatures and decreases ambulatory BP among elderly people, we conducted an open-label, simply randomized, controlled trial in the winters. As an intervention, the participants were asked to set the heating device in the living room to start 1 h before estimated rising time with target temperature at 24°C, and to stay in the living room until 2 h after rising as long as possible. Repeatedly measured ambulatory BP, physical activity, and indoor temperatures until 4 h after rising were assessed using multilevel linear regression model with random intercept among individual. A total of 359 eligible participants (mean age ± standard deviation: 71.6 ± 6.6) were randomly allocated to the control group (n = 173) and intervention group (n = 186). Intervention significantly increased living room temperature by 2.09°C (95% confidence interval 1.28-2.90), and significantly decreased SBP and DBP by 4.43/2.33 mmHg (95% confidence interval 0.97-7.88/0.08-4.58 mmHg) after adjusting for confounders including age, sex, antihypertensive medication, household income, and physical activity. Short-term effect of instruction in home heating showed larger increase of indoor temperature than that of insulation intervention. Significant reduction of BPsuggests the effectiveness on preventing cardiovascular incidence in winter. To summarize, instruction in heating significantly decreased BP.

  17. Sentence retrieval for abstracts of randomized controlled trials

    Directory of Open Access Journals (Sweden)

    Chung Grace Y

    2009-02-01

    Full Text Available Abstract Background The practice of evidence-based medicine (EBM requires clinicians to integrate their expertise with the latest scientific research. But this is becoming increasingly difficult with the growing numbers of published articles. There is a clear need for better tools to improve clinician's ability to search the primary literature. Randomized clinical trials (RCTs are the most reliable source of evidence documenting the efficacy of treatment options. This paper describes the retrieval of key sentences from abstracts of RCTs as a step towards helping users find relevant facts about the experimental design of clinical studies. Method Using Conditional Random Fields (CRFs, a popular and successful method for natural language processing problems, sentences referring to Intervention, Participants and Outcome Measures are automatically categorized. This is done by extending a previous approach for labeling sentences in an abstract for general categories associated with scientific argumentation or rhetorical roles: Aim, Method, Results and Conclusion. Methods are tested on several corpora of RCT abstracts. First structured abstracts with headings specifically indicating Intervention, Participant and Outcome Measures are used. Also a manually annotated corpus of structured and unstructured abstracts is prepared for testing a classifier that identifies sentences belonging to each category. Results Using CRFs, sentences can be labeled for the four rhetorical roles with F-scores from 0.93–0.98. This outperforms the use of Support Vector Machines. Furthermore, sentences can be automatically labeled for Intervention, Participant and Outcome Measures, in unstructured and structured abstracts where the section headings do not specifically indicate these three topics. F-scores of up to 0.83 and 0.84 are obtained for Intervention and Outcome Measure sentences. Conclusion Results indicate that some of the methodological elements of RCTs are

  18. Target-controlled infusion of remifentanil with or without flurbiprofen axetil in sedation for extracorporeal shock wave lithotripsy of pancreatic stones: a prospective, open-label, randomized controlled trial.

    Science.gov (United States)

    Yang, Yu-Guang; Hu, Liang-Hao; Chen, Hui; Li, Bo; Fan, Xiao-Hua; Li, Jin-Bao; Wang, Jia-Feng; Deng, Xiao-Ming

    2015-11-07

    Extracorporeal shock wave lithotripsy (ESWL) is an effective therapeutic method used to treat patients with pancreatic stones. However, the anesthesia for this procedure has been underappreciated, with minimal reports of these procedures in certain case series with general or epidural anesthesia. A cohort of 60 patients who elected to undergo ESWL in order to treat pancreatic stones for the first time were randomly selected and divided into two groups. One group of patients received target controlled infusion (TCI) of remifentanil, while the other group of patients received TCI of remifentanil plus a bolus of flurbiprofen axetil (a cyclooxygenase inhibitor) (Rem group and Rem + Flu group, n = 30 for each group). The Dixon's up-and-down method was used to calculate the half maximum effective concentration (EC50) of remifentanil. Visual analogue scales of pain, Ramsay sedation scale, hemodynamic changes, and adverse events were also recorded. The EC50 of remifentanil was calculated to be 4.0 ng/ml (95 % confidential interval: 3.84 ng/ml, 4.16 ng/ml) and 2.76 ng/ml (95 % confidential interval: 2.63 ng/ml, 2.89 ng/ml) in the Rem group and Rem + Flu group respectively (p flurbiprofen axetil provided satisfactory analgesia and sedation for ESWL of pancreatic stones with less adverse events. (Clinicaltrial.gov: NCT01998217 ; registered on November 19, 2013).

  19. Moxibustion for pain relief in patients with primary dysmenorrhea: A randomized controlled trial

    Science.gov (United States)

    Bo, Linna; Lao, Lixing; Chen, Jiao; Yu, Siyi; Yu, Zheng; Tang, Hongzhi; Yi, Ling; Wu, Xi; Yang, Jie; Liang, Fanrong

    2017-01-01

    Background Though moxibustion is frequently used to treat primary dysmenorrhea in China, relevant evidence supporting its effectiveness is still scanty. Methods This study was a pragmatic randomized, conventional drug controlled, open-labeled clinical trial. After initial screen, 152 eligible participants were averagely randomized to receive two different treatment strategies: Moxibustion and conventional drugs. Participants and practitioners were not blinded in this study. The duration of each treatment was 3 months. The primary outcome was pain relief measured by the Visual Analogue Scale. The menstrual pain severity was recorded in a menstrual pain diary. Results 152 eligible patients were included but only 133 of them eventually completed the whole treatment course. The results showed that the menstrual pain intensity in experimental group and control group was reduced from 6.38±1.28 and 6.41±1.29, respectively, at baseline, to 2.54±1.41 and 2.47±1.29 after treatment. The pain reduction was not significantly different between these two groups (P = 0.76), however; the pain intensity was significantly reduced relative to baseline for each group (P<0.01). Three months after treatment, the effectiveness of moxibustion sustained and started to be superior to the drug’s effect (-0.87, 95%CI -1.32 to -0.42, P<0.01). Secondary outcome analyses showed that moxibustion was as effective as drugs in alleviating menstrual pain-related symptoms. The serum levels of pain mediators, such as PGF2α, OT, vWF, β-EP, PGE2, were significantly improved after treatment in both groups (P<0.05). No adverse events were reported in this trial. Conclusions Both moxibustion and conventional drug showed desirable merits in managing menstrual pain, given their treatment effects and economic costs. This study as a pragmatic trial only demonstrates the effectiveness, not the efficacy, of moxibustion for menstrual pain. It can’t rule out the effect of psychological factors during

  20. Studies on quality control of technetium-99m labelling kits

    International Nuclear Information System (INIS)

    Kim, Jae Rok; Park, Kyung Bae; Awh, Ok Doo

    1987-12-01

    Various experiments for the quality control of Tc-99m labelled radiopharmaceuticals such as Tc-99m-phytate, Tc-99m-MDP, Tc-99m-Tin Colloid, Tc-99m-DISIDA, Tc-99m-DTPA,Tc-99m-DMSA, Tc-99m-Gulcoheptonate, TC-99m-Pyrophosphate, Tc-99m-HSA, and Tc-99m-HAM were carried out. Labelling yield and radiochemical purity of each of the instant labelling kit of KAERI made were determined by means of radiochromatography. Biodistribution in mice and whole body or specific organ imagings of rabbits were also carried out and discussed the relationship between the data of biodistributions and radiochemical purities. Labelling yeilds were above 98% for almost all of the labelling kits. The radio-pharmaceuticals were accumulated at each target organ with moderate specifities. In case of radiochemical purity of above 98%, the biodistribution and gamma imagings were also better. The kits of MDP and DISIDA were stable at least for four moths while the other kits at least eight months. (Author)

  1. Open versus laparoscopic pyloromyotomy for pyloric stenosis: a meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Jia, W-Q; Tian, J-H; Yang, K-H; Ma, B; Liu, Y-L; Zhang, P; Li, R-J; Jia, R-H

    2011-03-01

    Aim of the study was to compare the outcomes after laparoscopic pyloromyotomy (LP) with those of open pyloromyotomy (OP) for infantile pyloric stenosis. We conducted searches until February 2009 in multiple databases and identified randomized controlled trials comparing LP with OP for pyloric stenosis. Results were expressed using the odds ratio (OR) for categorical variables and standard weighted mean differences (SMD) for continuous outcomes. Study quality was assessed using the Cochrane Handbook 5.0.1 guidelines and statistical analysis was performed using RevMan 5.0.8 software. 3 studies totaling 492 infants were included. The results showed no significant differences in complications between the groups with regard to wound infection (OR: 1.77, 95% CI 0.58-5.35), mucosal perforations (OR: 0.96, 95% CI: 0.22-4.26), incisional hernia or granuloma (OR: 1.39, 95% CI: 0.41-4.73), incomplete pyloromyotomy (OR: 0.13, 95% CI: 0.02-1.07), substantial vomiting (OR: 0.67, 95% CI: 0.30-1.52) and total complications (OR: 0.91, 95% CI: 0.54-1.53). Although the combined result of 2 studies also indicated an insignificant discrepancy in time-related outcomes for full time to feeds, length of stay after surgery and operating time (SMD: 0.78, 95% CI: -0.50-2.06; SMD: 1.27, 95% CI: -1.56-4.10; SMD: -0.46, 95% CI: -1.11-0.20, respectively), another study indicated shorter times for LP procedures (p=0.002, 0.027, and 0.008, respectively). Only a few trials were available for analysis. Heterogeneity was seen between studies, but the available trials were of high quality. The present study shows that both OP and LP are equally safe and effective procedures for the management of pyloric stenosis in children. However, there was a trend in LP toward shorter time time-related outcomes. © Georg Thieme Verlag KG Stuttgart · New York.

  2. Efficacy of Atomoxetine for the Treatment of ADHD Symptoms in Patients with Pervasive Developmental Disorders: A Prospective, Open-Label Study

    Science.gov (United States)

    Fernandez-Jaen, Alberto; Fernandez-Mayoralas, Daniel Martin; Calleja-Perez, Beatriz; Munoz-Jareno, Nuria; Campos Diaz, Maria del Rosario; Lopez-Arribas, Sonia

    2013-01-01

    Objective: Atomoxetine's tolerance and efficacy were studied in 24 patients with pervasive developmental disorder and symptoms of ADHD. Method: Prospective, open-label, 16-week study was performed, using the variables of the Clinical Global Impression Scale and the Conners' Scale, among others. Results: A significant difference was found between…

  3. An Open-label Randomized Controlled Trial to Compare Weight Gain of Very Low Birth Weight Babies with or without Addition of Coconut Oil to Breast Milk.

    Science.gov (United States)

    Arun, Sumitha; Kumar, Manish; Paul, Thomas; Thomas, Nihal; Mathai, Sarah; Rebekah, Grace; Thomas, Niranjan

    2018-03-23

    Nutritional guidelines involving the feeding of very low birth weight babies (VLBW) recommend addition of Human Milk Fortifiers to breast milk. Owing to financial constraints, it is a practice in low- and middle-income countries (LMIC) to add coconut oil to aid better weight gain. There are inadequate data on improvement of growth parameters with oral coconut oil supplementation of breast milk. In this randomized controlled trial, we measured growth parameters and body composition of 60 babies who received either breast milk with coconut oil or breast milk alone. Randomization was stratified according to intrauterine growth appropriate for gestational age (n = 30) and small for gestational age (n = 30). There was no difference in weight gain between the two groups. The weight gain velocity was 15 ± 3.6 and 14.4 ± 3.4 g/kg/day (p value = 0.49) in the breast milk alone and in the breast milk with coconut oil group, respectively. There was no difference in increase in head circumference and length. Triceps skinfold thickness (n = 56) was similar in both groups, but subscapular skinfold thickness was significantly more in the coconut oil group. Total body fat percentage did not differ between the groups (25.2 ± 4.3 vs. 25.5 ± 4.3%, p = 0.79). Oral supplementation of coconut oil along with breast milk did not increase growth parameters or result in change in body composition in very low birth weight (VLBW) babies.

  4. Prevention of ICU delirium and delirium-related outcome with haloperidol: a study protocol for a multicenter randomized controlled trial

    Science.gov (United States)

    2013-01-01

    Background Delirium is a frequent disorder in intensive care unit (ICU) patients with serious consequences. Therefore, preventive treatment for delirium may be beneficial. Worldwide, haloperidol is the first choice for pharmacological treatment of delirious patients. In daily clinical practice, a lower dose is sometimes used as prophylaxis. Some studies have shown the beneficial effects of prophylactic haloperidol on delirium incidence as well as on mortality, but evidence for effectiveness in ICU patients is limited. The primary objective of our study is to determine the effect of haloperidol prophylaxis on 28-day survival. Secondary objectives include the incidence of delirium and delirium-related outcome and the side effects of haloperidol prophylaxis. Methods This will be a multicenter three-armed randomized, double-blind, placebo-controlled, prophylactic intervention study in critically ill patients. We will include consecutive non-neurological ICU patients, aged ≥18 years with an expected ICU length of stay >1 day. To be able to demonstrate a 15% increase in 28-day survival time with a power of 80% and alpha of 0.05 in both intervention groups, a total of 2,145 patients will be randomized; 715 in each group. The anticipated mortality rate in the placebo group is 12%. The intervention groups will receive prophylactic treatment with intravenous haloperidol 1 mg/q8h or 2 mg/q8h, and patients in the control group will receive placebo (sodium chloride 0.9%), both for a maximum period of 28-days. In patients who develop delirium, study medication will be stopped and patients will subsequently receive open label treatment with a higher (therapeutic) dose of haloperidol. We will use descriptive summary statistics as well as Cox proportional hazard regression analyses, adjusted for covariates. Discussion This will be the first large-scale multicenter randomized controlled prevention study with haloperidol in ICU patients with a high risk of delirium, adequately

  5. Tritiated bovine fibrinogen labelled in fibrinopeptide A region

    International Nuclear Information System (INIS)

    Wegrzynowicz, Z.; Kloczewiak, M.; Kopec, M.

    1974-01-01

    The method is described for labelling of bovine fibrinogen with 3 H-AcOAc. Preparations labelled at pH 7.8 with 10 to 40 molar excess of 3 H-AcOAc were found to contain 8 to 13 moles of acetyl residues per mole of fibrinogen. The content of clottable protein and UV spectra were unchanged as compared with control unlabelled preprations. The rate of clotting with thrombin was only slightly affected. The investigations on distribution of 3 H in products of proteolysis of 3 H-fibrinogen by thrombin and plasmin demonstrated a preferential labelling of fibrinopeptide A, absence of radioactive tracer in fibrinopeptide B, significantly higher specific radioactivity of fragment E than that of fragment D. Incorporation of the label into fibrinopeptide A opens the possibility for application of 3 H-fibrinogen as a convenient substrate for selective investigations on the enzymatic phase of clotting. (author)

  6. 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

  7. Randomized controlled trial of juzen-taiho-to in children with recurrent acute otitis media.

    Science.gov (United States)

    Ito, Makoto; Maruyama, Yumiko; Kitamura, Ken; Kobayashi, Toshimitsu; Takahashi, Haruo; Yamanaka, Noboru; Harabuchi, Yasuaki; Origasa, Hideki; Yoshizaki, Tomokazu

    2017-08-01

    Recurrent acute otitis media (AOM) in young children is rapidly increasing worldwide. Repeated antibiotic use leads to antibiotic-resistant pathogen development. Complementary and alternative medicine approaches have been suggested as a supplemental treatment option to conventional antimicrobial medicine. This randomized, parallel-group, open-label, non-herbal medicine controlled trial assessed the efficacy of a traditional Japanese herbal medicine, juzen-taiho-to (JTT) for AOM prevention in otitis-prone children. Children prone to recurrent AOM aged 6-48 months were recruited from 26 otolaryngology clinics in Japan and received conventional AOM treatment based on Japanese guidelines with or without 2 daily oral doses of JTT (0.10-0.25g/kg/day). The mean number of AOM episodes, coryza episodes, and duration of total antibiotic administration per month were compared during 3-month intervention. At least one episode of AOM was diagnosed in 71% of JTT-group and 92% of control participants during follow-up. JTT administration reduced the frequency of AOM episodes by 57% compared with children who received conventional treatment alone (0.61±0.54 vs. 1.07±0.72 AOM instances/month; P=0.005) and also significantly decreased number of coryza episodes (P=0.015) and total antibiotic administration (P=0.024). This is the first report of recurrent AOM prevention by herbal medication. JTT appears to effectively prevent recurrent AOM in children. Subsequent double-blind studies are needed to confirm the beneficial effects of JTT on recurrent AOM and upper respiratory tract infections. Copyright © 2016. Published by Elsevier B.V.

  8. The Ex-PRESS glaucoma shunt versus trabeculectomy in open-angle glaucoma: a prospective randomized study

    NARCIS (Netherlands)

    de Jong, Leo A. M. S.

    2009-01-01

    The purpose of this study was to establish the efficacy and safety of the Ex-PRESS (Optonol Ltd., Neve Ilan, Israel) mini glaucoma shunt in open-angle glaucoma. This was a prospective, randomized trial. Eyes from enrolled patients were randomly assigned to either Ex-PRESS implantation under a

  9. A randomized, double-blind, placebo-controlled study of omalizumab combined with oral immunotherapy for the treatment of cow's milk allergy.

    Science.gov (United States)

    Wood, Robert A; Kim, Jennifer S; Lindblad, Robert; Nadeau, Kari; Henning, Alice K; Dawson, Peter; Plaut, Marshall; Sampson, Hugh A

    2016-04-01

    Although studies of oral immunotherapy (OIT) for food allergy have shown promise, treatment is frequently complicated by adverse reactions and, even when successful, has limited long-term efficacy because benefits usually diminish when treatment is discontinued. We sought to examine whether the addition of omalizumab to milk OIT reduces treatment-related reactions, improves outcomes, or both. This was a double-blind, placebo-controlled trial with subjects randomized to omalizumab or placebo. Open-label milk OIT was initiated after 4 months of omalizumab/placebo with escalation to maintenance over 22 to 40 weeks, followed by daily maintenance dosing through month 28. At month 28, omalizumab was discontinued, and subjects passing an oral food challenge (OFC) continued OIT for 8 weeks, after which OIT was discontinued with rechallenge at month 32 to assess sustained unresponsiveness (SU). Fifty-seven subjects (7-32 years) were randomized, with no significant baseline differences in age, milk-specific IgE levels, skin test results, or OFC results. At month 28, 24 (88.9%) omalizumab-treated subjects and 20 (71.4%) placebo-treated subjects passed the 10-g "desensitization" OFC (P = .18). At month 32, SU was demonstrated in 48.1% in the omalizumab group and 35.7% in the placebo group (P = .42). Adverse reactions were markedly reduced during OIT escalation in omalizumab-treated subjects for percentages of doses per subject provoking symptoms (2.1% vs 16.1%, P = .0005), dose-related reactions requiring treatment (0.0% vs 3.8%, P = .0008), and doses required to achieve maintenance (198 vs 225, P = .008). In this first randomized, double-blind, placebo-controlled trial of omalizumab in combination with food OIT, we found significant improvements in measurements of safety but not in outcomes of efficacy (desensitization and SU). Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  10. Effect on attendance by including focused information on spirometry in preventive health checks: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Ørts, Lene Maria; Løkke, Anders; Bjerregaard, Anne-Louise; Maindal, Helle Terkildsen; Sandbæk, Annelli

    2016-12-01

    Early detection of lung diseases can help to reduce their severity. Lung diseases are among the most frequently occurring and serious diseases worldwide; nonetheless, many patients remain undiagnosed. Preventive health checks including spirometry can detect lung diseases at early stages; however, recruitment for health checks remains a challenge, and little is known about what motivates the attendance. The aim of the study is to examine whether focused information on spirometry in the invitation compared to general information will impact the attendance rate in preventive health checks. This randomized, controlled trial tests the effect of information on spirometry embedded in the Check your Health Preventive Program (CHPP). The CHPP is an open-label, household cluster-randomized, controlled trial offering a preventive health check to 30- to -49-year-olds in a Danish municipality from 2012 to 2017 (n = 26,216). During 2015-2016, 4356 citizens aged 30-49 years will be randomized into two groups. The intervention group receives an invitation which highlights the value and contents of spirometry as part of a health check and information about lung diseases. The comparison group receives a standard invitation containing practical information and specifies the contents of the general health check. Outcomes are (1) differences in attendance rates measured by the proportion of citizens attending each of the two study groups and (2) proportion of persons at risk defined by smoking status and self-reported lung symptoms in the study groups. The proportion of participants with abnormal spirometry assessed at the preventive health check will be compared between the two study groups. The results from the present study will inform future recruitment strategies to health checks. The developed material on content, value, and information about lung disease is feasible and transferable to other populations, making it easy to implement if effective. ClinicalTrials.gov: NCT

  11. 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...

  12. PySeqLab: an open source Python package for sequence labeling and segmentation.

    Science.gov (United States)

    Allam, Ahmed; Krauthammer, Michael

    2017-11-01

    Text and genomic data are composed of sequential tokens, such as words and nucleotides that give rise to higher order syntactic constructs. In this work, we aim at providing a comprehensive Python library implementing conditional random fields (CRFs), a class of probabilistic graphical models, for robust prediction of these constructs from sequential data. Python Sequence Labeling (PySeqLab) is an open source package for performing supervised learning in structured prediction tasks. It implements CRFs models, that is discriminative models from (i) first-order to higher-order linear-chain CRFs, and from (ii) first-order to higher-order semi-Markov CRFs (semi-CRFs). Moreover, it provides multiple learning algorithms for estimating model parameters such as (i) stochastic gradient descent (SGD) and its multiple variations, (ii) structured perceptron with multiple averaging schemes supporting exact and inexact search using 'violation-fixing' framework, (iii) search-based probabilistic online learning algorithm (SAPO) and (iv) an interface for Broyden-Fletcher-Goldfarb-Shanno (BFGS) and the limited-memory BFGS algorithms. Viterbi and Viterbi A* are used for inference and decoding of sequences. Using PySeqLab, we built models (classifiers) and evaluated their performance in three different domains: (i) biomedical Natural language processing (NLP), (ii) predictive DNA sequence analysis and (iii) Human activity recognition (HAR). State-of-the-art performance comparable to machine-learning based systems was achieved in the three domains without feature engineering or the use of knowledge sources. PySeqLab is available through https://bitbucket.org/A_2/pyseqlab with tutorials and documentation. ahmed.allam@yale.edu or michael.krauthammer@yale.edu. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

  13. 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

  14. Quality of Life in Childhood Epilepsy in pediatric patients enrolled in a prospective, open-label clinical study with cannabidiol.

    Science.gov (United States)

    Rosenberg, Evan C; Louik, Jay; Conway, Erin; Devinsky, Orrin; Friedman, Daniel

    2017-08-01

    Recent clinical trials indicate that cannabidiol (CBD) may reduce seizure frequency in pediatric patients with certain forms of treatment-resistant epilepsy. Many of these patients experience significant impairments in quality of life (QOL) in physical, mental, and social dimensions of health. In this study, we measured the caregiver-reported Quality of Life in Childhood Epilepsy (QOLCE) in a subset of patients enrolled in a prospective, open-label clinical study of CBD. Results from caregivers of 48 patients indicated an 8.2 ± 9.9-point improvement in overall patient QOLCE (p < 0.001) following 12 weeks of CBD. Subscores with improvement included energy/fatigue, memory, control/helplessness, other cognitive functions, social interactions, behavior, and global QOL. These differences were not correlated to changes in seizure frequency or adverse events. The results suggest that CBD may have beneficial effects on patient QOL, distinct from its seizure-reducing effects; however, further studies in placebo-controlled, double-blind trials are necessary to confirm this finding. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  15. 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

  16. 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

  17. 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.

  18. The Influence of Sugar-Sweetened Beverage Health Warning Labels on Parents' Choices.

    Science.gov (United States)

    Roberto, Christina A; Wong, Diandra; Musicus, Aviva; Hammond, David

    2016-02-01

    US states have introduced bills requiring sugar-sweetened beverages (SSBs) to display health warning labels. This study examined how such labels may influence parents and which labels are most impactful. In this study, 2381 demographically and educationally diverse parents participated in an online survey. Parents were randomly assigned to 1 of 6 conditions: (1) no warning label (control); (2) calorie label; or (3-6) 1 of 4 text versions of a warning label (eg, Safety Warning: Drinking beverages with added sugar[s] contributes to obesity, diabetes, and tooth decay). Parents chose a beverage for their child in a vending machine choice task, rated perceptions of different beverages, and indicated interest in receiving beverage coupons. Regression analyses controlling for frequency of beverage purchases were used to compare the no warning label group, calorie label group, and all warning label groups combined. Significantly fewer parents chose an SSB for their child in the warning label condition (40%) versus the no label (60%) and calorie label conditions (53%). Parents in the warning label condition also chose significantly fewer SSB coupons, believed that SSBs were less healthy for their child, and were less likely to intend to purchase SSBs. All P values parents' understanding of health harms associated with overconsumption of such beverages and may reduce parents' purchase of SSBs for their children. Copyright © 2016 by the American Academy of Pediatrics.

  19. Assessment of a Standardized Pre-Operative Telephone Checklist Designed to Avoid Late Cancellation of Ambulatory Surgery: The AMBUPROG Multicenter Randomized Controlled Trial.

    Directory of Open Access Journals (Sweden)

    Sonia Gaucher

    Full Text Available To assess the impact of a standardized pre-operative telephone checklist on the rate of late cancellations of ambulatory surgery (AMBUPROG trial.Multicenter, two-arm, parallel-group, open-label randomized controlled trial.11 university hospital ambulatory surgery units in Paris, France.Patients scheduled for ambulatory surgery and able to be reached by telephone.A 7-item checklist designed to prevent late cancellation, available in five languages and two versions (for children and adults, was administered between 7 and 3 days before the planned date of surgery, by an automated phone system or a research assistant. The control group received standard management alone.Rate of cancellation on the day of surgery or the day before.The study population comprised 3900 patients enrolled between November 2012 and September 2013: 1950 patients were randomized to the checklist arm and 1950 patients to the control arm. The checklist was administered to 68.8% of patients in the intervention arm, 1002 by the automated phone system and 340 by a research assistant. The rate of late cancellation did not differ significantly between the checklist and control arms (109 (5.6% vs. 113 (5.8%, adjusted odds ratio [95% confidence interval] = 0.91 [0.65-1.29], (p = 0.57. Checklist administration revealed that 355 patients (28.0% had not undergone tests ordered by the surgeon or anesthetist, and that 254 patients (20.0% still had questions concerning the fasting state.A standardized pre-operative telephone checklist did not avoid late cancellations of ambulatory surgery but enabled us to identify several frequent causes.ClinicalTrials.gov NCT01732159.

  20. Impact of diet and nutraceutical supplementation on inflammation in elderly people. Results from the RISTOMED study, an open-label randomized control trial.

    Science.gov (United States)

    Ostan, R; Béné, M C; Spazzafumo, L; Pinto, A; Donini, L M; Pryen, F; Charrouf, Z; Valentini, L; Lochs, H; Bourdel-Marchasson, I; Blanc-Bisson, C; Buccolini, F; Brigidi, P; Franceschi, C; d'Alessio, P A

    2016-08-01

    Eating habits may influence the life span and the quality of ageing process by modulating inflammation. The RISTOMED project was developed to provide a personalized and balanced diet, enriched with or without nutraceutical compounds, to decrease and prevent inflammageing, oxidative stress and gut microbiota alteration in healthy elderly people. This paper focused on the effect on inflammation and metabolism markers after 56 days of RISTOMED diet alone or supplementation with three nutraceutical compounds. A cohort of 125 healthy elderly subjects was recruited and randomized into 4 arms (Arm A, RISTOMED diet; Arm B, RISTOMED diet plus VSL#3 probiotic blend; Arm C, RISTOMED diet plus AISA d-Limonene; Arm D, RISTOMED diet plus Argan oil). Inflammatory and metabolism parameters as well as the ratio between Clostridium cluster IV and Bifidobacteria (CL/B) were collected before and after 56 days of dietary intervention, and their evolution compared among the arms. Moreover, participants were subdivided according to their baseline inflammatory parameters (erythrocytes sedimentation rate (ESR), C-Reactive Protein, fibrinogen, Tumor Necrosis Factor-alfa (TNF-α), and Interleukin 6) in two clusters with low or medium-high level of inflammation. The evolution of the measured parameters was then examined separately in each cluster. Overall, RISTOMED diet alone or with each nutraceutical supplementation significantly decreased ESR. RISTOMED diet supplemented with d-Limonene resulted in a decrease in fibrinogen, glucose, insulin levels and HOMA-IR. The most beneficial effects were observed in subjects with a medium-high inflammatory status who received RISTOMED diet with AISA d-Limonene supplementation. Moreover, RISTOMED diet associated with VSL#3 probiotic blend induced a decrease in the CL/B ratio. Overall, this study emphasizes the beneficial anti-inflammageing effect of RISTOMED diet supplemented with nutraceuticals to control the inflammatory status of elderly

  1. labelling and quality control of some 99m Tc-radiopharmaceuticals of expected biological activity

    International Nuclear Information System (INIS)

    Abdallah, A.B.I.

    2009-01-01

    this thesis addresses the labelling and quality control of some 99m Tc-radiopharmaceuticals which could be used for infection imaging. this study focuses on the labelling of sarafloxation, gatifloxation and cefepine with technetium-99m and biological evaluation of these labeled complexes and biodistribution in both normal and inflamed mice. the thesis is organized into two chapters: chapter I :labelling of some antibiotics chapter II :biological evaluation.

  2. The effect of reflexotherapy and massage therapy on vital signs and stress before coronary angiography: An open-label clinical trial.

    Science.gov (United States)

    Khaledifar, Ali; Nasiri, Marzeih; Khaledifar, Borzoo; Khaledifar, Arsalan; Mokhtari, Ali

    2017-03-01

    Complementary medicine interventions are now successfully used to reduce stress as well as to stabilize hemodynamic indices within different procedures. The present study aimed to examine the effect of massage therapy and reflexotherapy on reducing stress in patients before coronary angiography. In this open-label clinical trial, 75 consecutive patients who were candidate for coronary angiography were randomly assigned to receive reflexotherapy (n = 25), or massage therapy (n = 25), or routine care (n = 25) before angiography. The Spielberger State-Trait Anxiety Inventory was used to determine the stress level of patients before and after interventions and vital signs were also measured. Improvement in diastolic blood pressure, heart rate, and respiratory rate was shown in the reflexotherapy group, and similar effects were observed following other interventions including massage therapy and routine resting program. In subjects who received reflexotherapy the level of stress decreased slightly compared with the other two groups. However, following interventions the level of stress in reflexotherapy group was shown to be lower than other study groups. Reflexotherapy before coronary angiography can help to stabilize vital sign as well as reduce the level of stress. The effect of massage therapy was limited to reducing stress.

  3. Effect of minoxidil topical foam on frontotemporal and vertex androgenetic alopecia in men: a 104-week open-label clinical trial.

    Science.gov (United States)

    Kanti, V; Hillmann, K; Kottner, J; Stroux, A; Canfield, D; Blume-Peytavi, U

    2016-07-01

    Topical minoxidil formulations have been shown to be effective in treating androgenetic alopecia (AGA) for 12 months. Efficacy and safety in both frontotemporal and vertex regions over longer application periods have not been studied so far. To evaluate the effect of 5% minoxidil topical foam (5% MTF) in the frontotemporal and vertex areas in patients with moderate AGA over 104 weeks. An 80-week, open-label extension phase was performed, following a 24-week randomized, double-blind, placebo-controlled study in men with AGA grade IIIvertex to VI. Group 1 (n = 22) received ongoing 5% MTF for 104 weeks, Group 2 (n = 23) received placebo topical foam (plaTF) until week 24, followed by 5% MTF until week 104 during the extension phase. Frontotemporal and vertex target area non-vellus hair counts (f-TAHC, v-TAHC) and cumulative hair width (f-TAHW, v-TAHW) were assessed at baseline and at weeks 24, 52, 76 and 104. In Group 1, f-TAHW and f-TAHC showed a statistically significant increase from baseline to week 52 and week 76, respectively, returning to values comparable to baseline at week 104. No significant differences were found between baseline and week 104 in v-TAHC in Group 1 as well as f-TAHC, v-TAHC, f-TAHW and v-TAHW values in Group 2. 5% MTF is effective in stabilizing hair density, hair width and scalp coverage in both frontotemporal and vertex areas over an application period of 104 weeks, while showing a good safety and tolerability profile with a low rate of irritant contact dermatitis. © 2015 European Academy of Dermatology and Venereology.

  4. A randomized controlled open trial of population-based disease and case management in a Medicare Plus Choice health maintenance organization.

    Science.gov (United States)

    Martin, David C; Berger, Marc L; Anstatt, David T; Wofford, Jonathan; Warfel, DeAnn; Turpin, Robin S; Cannuscio, Carolyn C; Teutsch, Steven M; Mansheim, Bernard J

    2004-10-01

    The object of this study was to examine the effect of population-based disease management and case management on resource use, self-reported health status, and member satisfaction with and retention in a Medicare Plus Choice health maintenance organization (HMO). Study design consisted of a prospective, randomized controlled open trial of 18 months' duration. Participants were 8504 Medicare beneficiaries aged 65 and older who had been continuously enrolled for at least 12 months in a network model Medicare Plus Choice HMO serving a contiguous nine-county metropolitan area. Members were care managed with an expert clinical information system and frequent telephone contact. Main outcomes included self-reported health status measured by the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), resource use measured by admission rates and bed-days per thousand per year, member satisfaction, and costs measured by paid claims. More favorable outcomes occurred in the intervention group for satisfaction with the health plan (P management and case management led to improved self-reported satisfaction and social function but not to a global net decrease in resource use or improved member retention.

  5. Effectiveness of Chinese massage therapy (Tui Na) for chronic low back pain: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Yang, Mingxiao; Feng, Yue; Pei, Hong; Deng, Shufang; Wang, Minyu; Xiao, Xianjun; Zheng, Hui; Lai, Zhenhong; Chen, Jiao; Li, Xiang; He, Xiaoguo; Liang, Fanrong

    2014-10-29

    Low back pain is a common, disabling musculoskeletal disorder in both developing and developed countries. Although often recommended, the potential efficacy of massage therapy in general, and Chinese massage (tuina) in particular, for relief of chronic low back pain (CLBP) has not been fully established due to inadequate sample sizes, low methodological quality, and subclinical dosing regimens of trials to date. Thus, the purpose of this randomized controlled trial (RCT) is to evaluate the comparative effectiveness of tuina massage therapy versus conventional analgesics for CLBP. The present study is a single center, two-arm, open-label RCT. A total of 150 eligible CLBP patients will be randomly assigned to either a tuina treatment group or a conventional drug control group in a 1:1 ratio. Patients in the tuina group receive a 20 minutes, 4-step treatment protocol which includes both structural and relaxation massage, administered in 20 sessions over a period of 4 weeks. Patients in the conventional drug control group are instructed to take a specific daily dose of ibuprofen. The primary outcome measure is the change from baseline back pain and function, measured by Roland-Morris Disability Questionnaire, at two months. Secondary outcome measures include the visual analogue scale, Japanese orthopedic association score (JOAS), and McGill pain questionnaire. The design and methodological rigor of this trial will allow for collection of valuable data to evaluate the efficacy of a specific tuina protocol for treating CLBP. This trial will therefore contribute to providing a solid foundation for clinical treatment of CLBP, as well as future research in massage therapy. This trial was registered with ClinicalTrials.gov of the National Institute of Health on 22 October 2013 (http://NCT01973010).

  6. A Randomized Controlled Trial of Vildagliptin Versus Alogliptin: Effective Switch From Sitagliptin in Patients With Type 2 Diabetes.

    Science.gov (United States)

    Shigematsu, Erina; Yamakawa, Tadashi; Oba, Mari S; Suzuki, Jun; Nagakura, Jo; Kadonosono, Kazuaki; Terauchi, Yasuo

    2017-07-01

    We investigated the effects of vildagliptin or alogliptin on blood glucose and hemoglobin A1c (HbA1c) in patients with type 2 diabetes inadequately controlled by sitagliptin. In a single-center open-label trial, 35 patients with inadequate glycemic control on sitagliptin therapy (50 mg once daily) were randomly switched to treatment with vildagliptin (50 mg twice daily) or alogliptin (25 mg once daily). After 12 weeks, patients who failed to achieve the target HbA1c level of vildagliptin or alogliptin treatment were switched to high-dose sitagliptin (100 mg once daily) and the effect on glycemic control was assessed. Vildagliptin did not significantly alter the mean plasma glucose level (175.5 ± 54.4 mg/dL vs. 179.1 ± 73.4 mg/dL) or HbA1c (8.01% vs. 8.02%) after 12 weeks. With alogliptin, mean plasma glucose increased from 175.4 ± 50.9 mg/dL to 195.3 ± 55.0 mg/dL after 12 weeks and HbA1c increased significantly from 8.0% to 8.3% (P vildagliptin to high-dose sitagliptin (100 mg daily), HbA1c was increased to 8.3%, but it was significantly (P vildagliptin group than the alogliptin group (P = 0.008), but the response rate (achieving the target HbA1c vildagliptin, alogliptin, and sitagliptin) were different, and the effects of vildagliptin and sitagliptin were stronger than that of alogliptin.

  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. 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

  9. Open lung approach versus standard protective strategies: Effects on driving pressure and ventilatory efficiency during anesthesia - A pilot, randomized controlled trial.

    Science.gov (United States)

    Ferrando, Carlos; Suarez-Sipmann, Fernando; Tusman, Gerardo; León, Irene; Romero, Esther; Gracia, Estefania; Mugarra, Ana; Arocas, Blanca; Pozo, Natividad; Soro, Marina; Belda, Francisco J

    2017-01-01

    Low tidal volume (VT) during anesthesia minimizes lung injury but may be associated to a decrease in functional lung volume impairing lung mechanics and efficiency. Lung recruitment (RM) can restore lung volume but this may critically depend on the post-RM selected PEEP. This study was a randomized, two parallel arm, open study whose primary outcome was to compare the effects on driving pressure of adding a RM to low-VT ventilation, with or without an individualized post-RM PEEP in patients without known previous lung disease during anesthesia. Consecutive patients scheduled for major abdominal surgery were submitted to low-VT ventilation (6 ml·kg-1) and standard PEEP of 5 cmH2O (pre-RM, n = 36). After 30 min estabilization all patients received a RM and were randomly allocated to either continue with the same PEEP (RM-5 group, n = 18) or to an individualized open-lung PEEP (OL-PEEP) (Open Lung Approach, OLA group, n = 18) defined as the level resulting in maximal Cdyn during a decremental PEEP trial. We compared the effects on driving pressure and lung efficiency measured by volumetric capnography. OL-PEEP was found at 8±2 cmH2O. 36 patients were included in the final analysis. When compared with pre-RM, OLA resulted in a 22% increase in compliance and a 28% decrease in driving pressure when compared to pre-RM. These parameters did not improve in the RM-5. The trend of the DP was significantly different between the OLA and RM-5 groups (p = 0.002). VDalv/VTalv was significantly lower in the OLA group after the RM (p = 0.035). Lung recruitment applied during low-VT ventilation improves driving pressure and lung efficiency only when applied as an open-lung strategy with an individualized PEEP in patients without lung diseases undergoing major abdominal surgery. ClinicalTrials.gov NCT02798133.

  10. Open lung approach versus standard protective strategies: Effects on driving pressure and ventilatory efficiency during anesthesia - A pilot, randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Carlos Ferrando

    Full Text Available Low tidal volume (VT during anesthesia minimizes lung injury but may be associated to a decrease in functional lung volume impairing lung mechanics and efficiency. Lung recruitment (RM can restore lung volume but this may critically depend on the post-RM selected PEEP. This study was a randomized, two parallel arm, open study whose primary outcome was to compare the effects on driving pressure of adding a RM to low-VT ventilation, with or without an individualized post-RM PEEP in patients without known previous lung disease during anesthesia.Consecutive patients scheduled for major abdominal surgery were submitted to low-VT ventilation (6 ml·kg-1 and standard PEEP of 5 cmH2O (pre-RM, n = 36. After 30 min estabilization all patients received a RM and were randomly allocated to either continue with the same PEEP (RM-5 group, n = 18 or to an individualized open-lung PEEP (OL-PEEP (Open Lung Approach, OLA group, n = 18 defined as the level resulting in maximal Cdyn during a decremental PEEP trial. We compared the effects on driving pressure and lung efficiency measured by volumetric capnography.OL-PEEP was found at 8±2 cmH2O. 36 patients were included in the final analysis. When compared with pre-RM, OLA resulted in a 22% increase in compliance and a 28% decrease in driving pressure when compared to pre-RM. These parameters did not improve in the RM-5. The trend of the DP was significantly different between the OLA and RM-5 groups (p = 0.002. VDalv/VTalv was significantly lower in the OLA group after the RM (p = 0.035.Lung recruitment applied during low-VT ventilation improves driving pressure and lung efficiency only when applied as an open-lung strategy with an individualized PEEP in patients without lung diseases undergoing major abdominal surgery.ClinicalTrials.gov NCT02798133.

  11. The effects of individual upper alpha neurofeedback in ADHD: an open-label pilot study.

    Science.gov (United States)

    Escolano, C; Navarro-Gil, M; Garcia-Campayo, J; Congedo, M; Minguez, J

    2014-12-01

    Standardized neurofeedback (NF) protocols have been extensively evaluated in attention-deficit/hyperactivity disorder (ADHD). However, such protocols do not account for the large EEG heterogeneity in ADHD. Thus, individualized approaches have been suggested to improve the clinical outcome. In this direction, an open-label pilot study was designed to evaluate a NF protocol of relative upper alpha power enhancement in fronto-central sites. Upper alpha band was individually determined using the alpha peak frequency as an anchor point. 20 ADHD children underwent 18 training sessions. Clinical and neurophysiological variables were measured pre- and post-training. EEG was recorded pre- and post-training, and pre- and post-training trials within each session, in both eyes closed resting state and eyes open task-related activity. A power EEG analysis assessed long-term and within-session effects, in the trained parameter and in all the sensors in the (1-30) Hz spectral range. Learning curves over sessions were assessed as well. Parents rated a clinical improvement in children regarding inattention and hyperactivity/impulsivity. Neurophysiological tests showed an improvement in working memory, concentration and impulsivity (decreased number of commission errors in a continuous performance test). Relative and absolute upper alpha power showed long-term enhancement in task-related activity, and a positive learning curve over sessions. The analysis of within-session effects showed a power decrease ("rebound" effect) in task-related activity, with no significant effects during training trials. We conclude that the enhancement of the individual upper alpha power is effective in improving several measures of clinical outcome and cognitive performance in ADHD. This is the first NF study evaluating such a protocol in ADHD. A controlled evaluation seems warranted due to the positive results obtained in the current study.

  12. Effects of professional oral health care on elderly: randomized trial.

    Science.gov (United States)

    Morino, T; Ookawa, K; Haruta, N; Hagiwara, Y; Seki, M

    2014-11-01

    To better understand the role of the professional oral health care for elderly in improving geriatric oral health, the effects of short-term professional oral health care (once per week for 1 month) on oral microbiological parameters were assessed. Parallel, open-labelled, randomize-controlled trial was undertaken in a nursing home for elderly in Shizuoka, Japan. Thirty-four dentate elderly over 74 years were randomly assigned from ID number to the intervention (17/34) and control (17/34) groups. The outcomes were changes in oral microbiological parameters (number of bacteria in unstimulated saliva; whole bacteria, Streptococcus, Fusobacterium and Prevotella: opportunistic pathogens detection: and index of oral hygiene evaluation [Dental Plaque Index, DPI]) within the intervention period. Each parameter was evaluated at before and after intervention period. Four elderly were lost from mortality (1), bone fracture (1), refused to participate (1) and multi-antibiotics usage (1). Finally, 30 elderly were analysed (14/intervention and 16/control). At baseline, no difference was found between the control and intervention groups. After the intervention period, the percentage of Streptococcus species increased significantly in the intervention group (Intervention, 86% [12/14]; Control, 50% [8/16]: Fisher's, right-tailed, P oral health care can improve oral conditions in the elderly. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Promoting the purchase of low-calorie foods from school vending machines: a cluster-randomized controlled study.

    Science.gov (United States)

    Kocken, Paul L; Eeuwijk, Jennifer; Van Kesteren, Nicole M C; Dusseldorp, Elise; Buijs, Goof; Bassa-Dafesh, Zeina; Snel, Jeltje

    2012-03-01

    Vending machines account for food sales and revenue in schools. We examined 3 strategies for promoting the sale of lower-calorie food products from vending machines in high schools in the Netherlands. A school-based randomized controlled trial was conducted in 13 experimental schools and 15 control schools. Three strategies were tested within each experimental school: increasing the availability of lower-calorie products in vending machines, labeling products, and reducing the price of lower-calorie products. The experimental schools introduced the strategies in 3 consecutive phases, with phase 3 incorporating all 3 strategies. The control schools remained the same. The sales volumes from the vending machines were registered. Products were grouped into (1) extra foods containing empty calories, for example, candies and potato chips, (2) nutrient-rich basic foods, and (3) beverages. They were also divided into favorable, moderately unfavorable, and unfavorable products. Total sales volumes for experimental and control schools did not differ significantly for the extra and beverage products. Proportionally, the higher availability of lower-calorie extra products in the experimental schools led to higher sales of moderately unfavorable extra products than in the control schools, and to higher sales of favorable extra products in experimental schools where students have to stay during breaks. Together, availability, labeling, and price reduction raised the proportional sales of favorable beverages. Results indicate that when the availability of lower-calorie foods is increased and is also combined with labeling and reduced prices, students make healthier choices without buying more or fewer products from school vending machines. Changes to school vending machines help to create a healthy school environment. © 2012, American School Health Association.

  14. Random Finite Set Based Bayesian Filtering with OpenCL in a Heterogeneous Platform

    Directory of Open Access Journals (Sweden)

    Biao Hu

    2017-04-01

    Full Text Available While most filtering approaches based on random finite sets have focused on improving performance, in this paper, we argue that computation times are very important in order to enable real-time applications such as pedestrian detection. Towards this goal, this paper investigates the use of OpenCL to accelerate the computation of random finite set-based Bayesian filtering in a heterogeneous system. In detail, we developed an efficient and fully-functional pedestrian-tracking system implementation, which can run under real-time constraints, meanwhile offering decent tracking accuracy. An extensive evaluation analysis was carried out to ensure the fulfillment of sufficient accuracy requirements. This was followed by extensive profiling analysis to spot the potential bottlenecks in terms of execution performance, which were then targeted to come up with an OpenCL accelerated application. Video-throughput improvements from roughly 15 fps to 100 fps (6× were observed on average while processing typical MOT benchmark videos. Moreover, the worst-case frame processing yielded an 18× advantage from nearly 2 fps to 36 fps, thereby comfortably meeting the real-time constraints. Our implementation is released as open-source code.

  15. Effects of Different Types of Front-of-Pack Labelling Information on the Healthiness of Food Purchases-A Randomised Controlled Trial.

    Science.gov (United States)

    Neal, Bruce; Crino, Michelle; Dunford, Elizabeth; Gao, Annie; Greenland, Rohan; Li, Nicole; Ngai, Judith; Ni Mhurchu, Cliona; Pettigrew, Simone; Sacks, Gary; Webster, Jacqui; Wu, Jason HY

    2017-11-24

    Front-of-pack nutrition labelling may support healthier packaged food purchases. Australia has adopted a novel Health Star Rating (HSR) system, but the legitimacy of this choice is unknown. To define the effects of different formats of front-of-pack labelling on the healthiness of food purchases and consumer perceptions. Individuals were assigned at random to access one of four different formats of nutrition labelling-HSR, multiple traffic light labels (MTL), daily intake guides (DIG), recommendations/warnings (WARN)-or control (the nutrition information panel, NIP). Participants accessed nutrition information by using a smartphone application to scan the bar-codes of packaged foods, while shopping. The primary outcome was healthiness defined by the mean transformed nutrient profile score of packaged foods that were purchased over four weeks. The 1578 participants, mean age 38 years, 84% female recorded purchases of 148,727 evaluable food items. The mean healthiness of the purchases in the HSR group was non-inferior to MTL, DIG, or WARN (all p 0.07), but WARN resulted in healthier packaged food purchases (mean difference 0.87; 95% confidence interval 0.03 to 1.72; p = 0.04). HSR was perceived by participants as more useful than DIG, and easier to understand than MTL or DIG (all p food purchases.

  16. Nitrates and bone turnover (NABT) - trial to select the best nitrate preparation: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Bucur, Roxana C; Reid, Lauren S; Hamilton, Celeste J; Cummings, Steven R; Jamal, Sophie A

    2013-09-08

    Organic nitrates uncouple bone turnover, improve bone mineral density, and improve trabecular and cortical components of bone. These changes in turnover, strength and geometry may translate into an important reduction in fractures. However, before proceeding with a large fracture trial, there is a need to identify the nitrate formulation that has both the greatest efficacy (with regards to bone turnover markers) and gives the fewest headaches. Ascertaining which nitrate formulation this may be is the purpose of the current study. This will be an open-label randomized, controlled trial conducted at Women's College Hospital comparing five formulations of nitrates for their effects on bone turnover markers and headache. We will recruit postmenopausal women age 50 years or older with no contraindications to nitroglycerin. Our trial will consist of a run-in phase and a treatment phase. We will enroll 420 women in the run-in phase, each to receive all of the 5 potential treatments in random order for 2 days, each with a 2-day washout period between treatments. Those who tolerate all formulations will enter the 12-week treatment phase and be randomly assigned to one of five groups: 0.3 mg sublingual nitroglycerin tablet, 0.6 mg of the sublingual tablet, a 20 mg tablet of isosorbide mononitrate, a 160 mg nitroglycerin transdermal patch (used for 8 h), and 15 mg of nitroglycerin ointment as used in a previous trial by our group. We will continue enrolment until we have randomized 210 women or 35 women per group. Concentrations of bone formation (bone-specific alkaline phosphatase and procollagen type I N-terminal propeptide) and bone resorption (C-telopeptides of collagen crosslinks and N-terminal crosslinks of collagen) agents will be measured in samples taken at study entry (the start of the run in phase) and 12 weeks. Subjects will record the frequency and severity of headaches daily during the run-in phase and then monthly after that. We will use the 'multiple

  17. Acupuncture Effect on Pain, Mouth Opening Limitation and on the Energy Meridians in Patients with Temporomandibular Dysfunction: A Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Vera LR. Zotelli

    2017-10-01

    Full Text Available Temporomandibular disorders (TMD, recognized as the most common conditions of chronic orofacial pain, have a multifactorial etiology. Acupuncture can help to relieve the pain and discomfort associated with these conditions, because it can rebalance the energy (Qi circulating in the meridians. The aim of the study was to verify the effectiveness of acupuncture in treating the pain; mouth opening limitation, and energy circulating in the meridians of patients with TMD of muscular or mixed origin. This was a controlled, randomized, double-blind clinical trial conducted at the Piracicaba Dental School (FOP/Unicamp, in Piracicaba SP, Brazil. The Treatment Group received acupuncture with real penetration of the needle, and the Placebo Group received a sham treatment without needle penetration. The acupoints used were: ST6, ST7, SI18, GV20, GB20, BL10, and LI4, during treatment performed for four weekly sessions. The TMD and mouth opening were evaluated according to the Research Diagnostic Criteria for Temporomandibular Disorders (RDC. The measurements of the energy at the meridians were performed by the Ryodoraku method, before and after acupuncture in all of the sessions in both groups. The results showed no decrease in pain in the Treatment Group when compared with the Placebo Group (p = 0.2261. There was no increase in the oral opening limit in the Treatment Group compared with the Placebo Group (p > 0.05. Regarding the energy levels, after acupuncture, there was a decrease in Yang energy in all sessions (p < 0.05, in both groups, however, only real acupuncture was effective in maintaining the Yin energy average throughout the four sessions, with significant difference between groups (p = 0.0198. In conclusion, volunteers with TMD presented a pattern of energy deficiency and the most prevalent imbalance patterns identified were in the meridians coupled to the kidney and bladder, and in the Shao Yin (heart/kidney and Shao Yang (triple

  18. A Multicenter, Randomized, Open-Labeled, Parallel Group Trial of Sildenafil in Alcohol-Associated Erectile Dysfunction: The Impact on Psychosocial Outcomes

    Directory of Open Access Journals (Sweden)

    Alexander Grinshpoon

    2009-09-01

    Full Text Available To examine the effect of sildenafil on erectile dysfunction (ED and psychosocial outcomes in alcohol-dependent (AD men, 108 men with these diagnoses were randomly assigned to either take sildenafil (50 mg as add-on to standard treatment for AD, or the same treatment without sildenafil, for 12 weeks. Only 50 patients in sildenafil group and 51 in control group twice completed the International Index of Erectile Function (IIEF and a battery of self-report questionnaires. IIEF scores and psychosocial functioning, self-esteem and support from friends improved only for sildenafil-treated patients (P < 0.001. The high effect sizes suggest that the observed benefits are unlikely to be a placebo effect, although their unspecific nature could not be ruled out. In men with ED associated with AD, sildenafil improves both ED and psychosocial outcomes. Further placebo-controlled clinical trial is warranted.

  19. Self-managed eHealth Disease Monitoring in Children and Adolescents with Inflammatory Bowel Disease: A Randomized Controlled Trial.

    Science.gov (United States)

    Carlsen, Katrine; Jakobsen, Christian; Houen, Gunnar; Kallemose, Thomas; Paerregaard, Anders; Riis, Lene B; Munkholm, Pia; Wewer, Vibeke

    2017-03-01

    To evaluate the impact of eHealth on disease activity, the need for hospital contacts, and medical adherence in children and adolescents with inflammatory bowel disease (IBD). Furthermore, to assess eHealth's influence on school attendance and quality of life (QoL). Patients with IBD, 10 to 17 years attending a public university hospital, were prospectively randomized to a 2-year open label case-controlled eHealth intervention. The eHealth-group used the web-application young.constant-care.com (YCC) on a monthly basis and in case of flare-ups, and were seen at one annual preplanned outpatient visit. The control-group continued standard visits every third month. Every 3 months, both groups had blood and fecal calprotectin tested and the following were assessed: escalation in medication, disease activity, hospital contacts, medical adherence, school absence, and QoL. Fifty-three patients in nonbiological treatment were included (27 eHealth/26 control). We found no differences between the groups regarding escalation in treatment and disease activity (symptoms, fecal calprotectin, and blood). The number of total outpatient visits (mean: eHealth 3.26, SEM 0.51; control 7.31, SEM 0.69; P eHealth 1.6, SEM 0.5; control 16.5, SEM 4.4; P eHealth-group. No differences in medical adherence and QoL were found. Adherence to YCC was 81% (384 of the 475 expected entries). None of the patients or parents felt unsafe using the eHealth system. The use of eHealth in children and adolescents with IBD is feasible, does not lead to impaired disease control, and can be managed by the patients without risk of increased disease activity.

  20. Effect on HBs antigen clearance of addition of pegylated interferon alfa-2a to nucleos(t)ide analogue therapy versus nucleos(t)ide analogue therapy alone in patients with HBe antigen-negative chronic hepatitis B and sustained undetectable plasma hepatitis B virus DNA: a randomised, controlled, open-label trial.

    Science.gov (United States)

    Bourlière, Marc; Rabiega, Pascaline; Ganne-Carrie, Nathalie; Serfaty, Lawrence; Marcellin, Patrick; Barthe, Yoann; Thabut, Dominique; Guyader, Dominique; Hezode, Christophe; Picon, Magali; Causse, Xavier; Leroy, Vincent; Bronowicki, Jean Pierre; Carrieri, Patrizia; Riachi, Ghassan; Rosa, Isabelle; Attali, Pierre; Molina, Jean Michel; Bacq, Yannick; Tran, Albert; Grangé, Jean Didier; Zoulim, Fabien; Fontaine, Hélène; Alric, Laurent; Bertucci, Inga; Bouvier-Alias, Magali; Carrat, Fabrice

    2017-03-01

    Findings from uncontrolled studies suggest that addition of pegylated interferon in patients with HBe antigen (HBeAg)-negative chronic hepatitis B receiving nucleos(t)ide analogues with undetectable plasma hepatitis B virus (HBV) DNA might increase HBs antigen (HBsAg) clearance. We aimed to assess this strategy. In this randomised, controlled, open-label trial, we enrolled patients aged 18-75 years with HBeAg-negative chronic hepatitis B and documented negative HBV DNA while on stable nucleos(t)ide analogue regimens for at least 1 year from 30 hepatology tertiary care wards in France. Patients had to have an alanine aminotransferase concentration of less than or equal to five times the upper normal range, no hepatocellular carcinoma, and a serum α fetoprotein concentration of less than 50 ng/mL, normal dilated fundus oculi examination, and a negative pregnancy test in women. Patients with contraindications to pegylated interferon were not eligible. A centralised randomisation used computer-generated lists of random permuted blocks of four with stratification by HBsAg titres (sida et les hépatites virales (France Recherche Nord&sud Sida-vih Hepatites). Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: results of a two-year open-label extension trial

    Directory of Open Access Journals (Sweden)

    Subha V. Raman

    2017-02-01

    Full Text Available Abstract Background Cardiomyopathy is a leading cause of morbidity and mortality in boys with Duchenne muscular dystrophy (DMD. We recently showed in a 12-month double-blind randomized controlled trial that adding eplerenone to background medical therapy was cardioprotective in this population. The objective of this study was to evaluate the safety and efficacy of longer-term eplerenone therapy in boys with DMD. Results Eleven subjects (phase 1 baseline median [range] age: 13 [7 – 25] years from the original 12-month trial at a single participating center were enrolled. Importantly, those who entered the extension study who had been on eplerenone previously were significantly older than those who had originally been on placebo (median age 10.5 vs. 18.0 years, p = 0.045. During an additional 24-month open-label extension study, all boys received eplerenone 25 mg orally once daily to treat preclinical DMD cardiomyopathy, defined as evident myocardial damage by late gadolinium enhancement cardiac magnetic resonance (LGE with preserved ejection fraction (EF. The threshold for potassium level, the primary safety measure, was not exceeded in any non-hemolyzed blood sample. Over 24 months, left ventricular (LV systolic strain, a more sensitive marker whose more negative values indicate greater contractility significantly improved (median change -4.4%, IQR -5.8 to -0.9% in younger subjects whereas older subjects’ strain remained stable without significant worsening or improvement (median change 0.2%, IQR -1.1 to 4.3%. EF and extent of myocardial damage by LGE remained stable in both groups over 2 years. Conclusions Eplerenone offers effective and safe cardioprotection for boys with DMD, particularly when started at a younger age. Eplerenone is a useful clinical therapeutic option, particularly if treatment is initiated earlier in life when cardiac damage is minimal. Trial registration http://ClinicalTrials.gov identifier NCT01521546

  2. Calorie labeling, fast food purchasing and restaurant visits.

    Science.gov (United States)

    Elbel, Brian; Mijanovich, Tod; Dixon, L Beth; Abrams, Courtney; Weitzman, Beth; Kersh, Rogan; Auchincloss, Amy H; Ogedegbe, Gbenga

    2013-11-01

    Obesity is a pressing public health problem without proven population-wide solutions. Researchers sought to determine whether a city-mandated policy requiring calorie labeling at fast food restaurants was associated with consumer awareness of labels, calories purchased and fast food restaurant visits. Difference-in-differences design, with data collected from consumers outside fast food restaurants and via a random digit dial telephone survey, before (December 2009) and after (June 2010) labeling in Philadelphia (which implemented mandatory labeling) and Baltimore (matched comparison city). Measures included: self-reported use of calorie information, calories purchased determined via fast food receipts, and self-reported weekly fast-food visits. The consumer sample was predominantly Black (71%), and high school educated (62%). Postlabeling, 38% of Philadelphia consumers noticed the calorie labels for a 33% point (P < 0.001) increase relative to Baltimore. Calories purchased and number of fast food visits did not change in either city over time. While some consumers report noticing and using calorie information, no population level changes were noted in calories purchased or fast food visits. Other controlled studies are needed to examine the longer term impact of labeling as it becomes national law. Copyright © 2013 The Obesity Society.

  3. 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.

  4. Chloroquine-Primaquine versus Chloroquine Alone to Treat Vivax Malaria in Afghanistan: An Open Randomized Superiority Trial.

    Science.gov (United States)

    Awab, Ghulam Rahim; Imwong, Mallika; Bancone, Germana; Jeeyapant, Atthanee; Day, Nicholas P J; White, Nicholas J; Woodrow, Charles J

    2017-12-01

    Afghanistan's national guidelines recommend primaquine (PQ) for radical treatment of Plasmodium vivax malaria, but this is rarely implemented because of concerns over potential hemolysis in patients who have G6PD deficiency. Between August 2009 and February 2014, we conducted an open-label, randomized controlled trial of chloroquine (CQ) alone versus chloroquine plus primaquine (0.25 mg base/kg/day for 14 days) (CQ+PQ) in patients aged 6 months and older with microscopy confirmed P. vivax infection. In the CQ+PQ group, G6PD deficiency was excluded by fluorescent spot testing. The primary outcome was P. vivax recurrence assessed by survival analysis over one year follow-up. Of 593 patients enrolled, 570 attended at or after 14 days of follow-up. Plasmodium vivax recurrences occurred in 37 (13.1%) of 282 patients in the CQ+PQ arm versus 86 (29.9%) of 288 in the CQ arm (Cox proportional hazard ratio [HR] 0.37, 95% confidence interval [CI] 0.25-0.54) (intention-to-treat analysis). Protection against recurrence was greater in the first 6 months of follow-up (HR 0.082; 95% CI 0.029-0.23) than later (HR 0.65, 95% CI 0.41-1.03). Five of seven patients requiring hospital admission were considered possible cases of PQ-related hemolysis, and PQ was stopped in a further six; however, in none of these cases did hemoglobin fall by ≥ 2 g/dL or to below 7 g/dL, and genotyping did not detect any cases of Mediterranean variant G6PD deficiency. PQ 0.25 mg/kg/day for 14 days prevents relapse of P. vivax in Afghanistan. Patient visits during the first week may improve adherence. Implementation will require deployment of point-of-care phenotypic tests for G6PD deficiency.

  5. Patient-reported genitourinary dysfunction after laparoscopic and open rectal cancer surgery in a randomized trial (COLOR II)

    DEFF Research Database (Denmark)

    Andersson, J; Abis, G; Gellerstedt, M

    2014-01-01

    BACKGROUND: This article reports on patient-reported sexual dysfunction and micturition symptoms following a randomized trial of laparoscopic and open surgery for rectal cancer. METHODS: Patients in the COLOR II randomized trial, comparing laparoscopic and open surgery for rectal cancer, completed...... laparoscopic and open approaches. An improvement in sexual dysfunction was seen in the first year, but some male sexual problems persisted. Before operation 64·5 per cent of men in the laparoscopic group and 55·6 per cent in the open group reported some degree of erectile dysfunction. This increased to 81...... radiotherapy, did not change these results. CONCLUSION: Sexual dysfunction is common in patients with rectal cancer, and treatment (including surgery) increases the proportion of patients affected. A laparoscopic approach does not change this. REGISTRATION NUMBER: NCT0029779 (http://www.clinicaltrials.gov)....

  6. A Randomized Double-Blind Sham-Controlled Study of Transcranial Direct Current Stimulation for Treatment-Resistant Major Depression

    Directory of Open Access Journals (Sweden)

    Daniel eBlumberger

    2012-08-01

    Full Text Available Objectives: Transcranial direct current stimulation (tDCS has demonstrated some efficacy in treatment-resistant major depression (TRD. The majority of previous controlled studies have used anodal stimulation to the left dorsolateral prefrontal cortex (DLPFC and a control location such as the supraorbital region on for the cathode. Several open label studies have suggested effectiveness from anodal stimulation to the left DLPFC combined with cathodal stimulation to the right DLPFC. Thus, this study evaluated the efficacy of tDCS using anodal stimulation to the left DLPFC and cathodal stimulation to the right DLPFC compared to sham tDCS. Methods: Subjects between the ages of 18 and 65 were recruited from a tertiary care university hospital. Twenty-four subjects with TRD and a 17-item Hamilton Depression Rating Scale (HDRS greater than 21 were randomized to receive tDCS or sham tDCS. The rates of remission were compared between the two treatment groups.Results: The remission rates did not differ significantly between the two groups using an intention to treat analysis. More subjects in the active tDCS group had failed a course of electroconvulsive therapy in the current depressive episode. Side effects did not differ between the two groups and in general the treatment was very well tolerated. Conclusion: Anodal stimulation to the left DLPFC and cathodal stimulation to the right DLPFC was not efficacious in TRD. However, a number of methodological limitations warrant caution in generalizing from this study. Ongoing, controlled studies should provide further clarification on the efficacy of this stimulation configuration in TRD.

  7. Influence of intravenous amifostine on xerostomia, tumor control, and survival after radiotherapy for head-and- neck cancer: 2-year follow-up of a prospective, randomized, phase III trial

    International Nuclear Information System (INIS)

    Wasserman, Todd H.; Brizel, David M.; Henke, Michael; Monnier, Alain; Eschwege, Francois; Sauer, Rolf; Strnad, Vratislav

    2005-01-01

    Purpose: To evaluate chronic xerostomia and tumor control 18 and 24 months after initial treatment with amifostine in a randomized controlled trial of patients with head-and-neck cancer; at 12 months after radiotherapy (RT), amifostine had been shown to reduce xerostomia without changing tumor control. Methods and Materials: Adults with head-and-neck cancer who underwent once-daily RT for 5-7 weeks (total dose, 50-70 Gy) received either open-label amifostine (200 mg/m 2 i.v.) 15-30 min before each fraction of radiation (n = 150) or RT alone (control; n = 153). Results: Amifostine administration was associated with a reduced incidence of Grade ≥2 xerostomia over 2 years of follow-up (p = 0.002), an increase in the proportion of patients with meaningful (>0.1 g) unstimulated saliva production at 24 months (p = 0.011), and reduced mouth dryness scores on a patient benefit questionnaire at 24 months (p < 0.001). Locoregional control rate, progression-free survival, and overall survival were not significantly different between the amifostine group and the control group. Conclusions: Amifostine administration during head-and-neck RT reduces the severity and duration of xerostomia 2 years after treatment and does not seem to compromise locoregional control rates, progression-free survival, or overall survival

  8. Labelling and quality control of somatostatin analogues with 99mTc

    International Nuclear Information System (INIS)

    Verdera, S.; Balter, H.; Rodriguez, G.; Robles, A.; Oliver, P.; Laiz, J.; Souto, B.

    2001-01-01

    Techniques and methodologies for labelling peptides with 99m Tc and methods for their purification, chemical, radiochemical and biological controls were evaluated. With the purpose of gaining experience, labelling with 125 I was also studied. RC-160 was labelled with 125 I using iodogen as well as chloramine-T method. Higher yields were obtained with chloramine-T method (60%), rendering 125 I-peptide with 98% of radiochemical purity, with specific activity of 240 μCi/μg - 274 μCi/μg. The product was stable for five weeks (at -20 deg. C). For somatostatin receptors studies rat brain cortex membrane was prepared. Maximum binding capacity was 24.7% and Kaff for the binding of RC-160 to receptor was estimated as 2.0x10 10 M -1 . Other peptides as β-(2-Naphthyl)- D Ala-Cys-Tyr- D Trp-Lys-Val-Cys-Thr amide (N-9642, Σ) and mouse epidermal growth factor (mEGF) were also labelled by means of limiting chloramine-T method. In case of mEGF the availability of membrane receptors allowed us to experiment in mice as well as in vitro. The reaction yields were up to 60% and 70% respectively. Biodistribution of 125 I-mEGF in a mouse with adenoma demonstrated preferential uptake in tumour (21,7% injected dose). The radioimmunoassay system gave 39% maximum binding (MB) and 50% displacement (ED 50 ) for 10 ng/mL unlabelled mEGF. Direct method and BFC's for labelling peptides with 99m Tc were investigated and purification and quality controls studies were performed by TLC, HPLC (UV and gamma detection). RC-160 was labelled by a direct method using sodium dithionite as reducing agent with radiochemical purity >95%. The product was stable up to six hours (at RT). Considerable adsorption problems were observed. Biological behavior was in accordance with the compounds' lipophilicity. The synthesis of TOC conjugates with HYNIC as BFC was done with 45%±5% (n=3) yield. Labelling of HYNIC-TOC with tricine as co-ligand was conducted with up to 90% yield. Studies of RC-160 labelling using

  9. 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...

  10. Label-controlled optical packet routing technologies and applications

    DEFF Research Database (Denmark)

    Koonen, A.M.J.; Yan, N.; Vegas Olmos, Juan José

    2007-01-01

    An overview is given of various optical packet labeling techniques. The architecture and technologies are discussed for optical packet routing nodes using orthogonal labeling with optoelectronic label processing, and for nodes using time-serial labeling with all-optical time-serial label processing...

  11. Cigarette warning label policy alternatives and smoking-related health disparities.

    Science.gov (United States)

    Thrasher, James F; Carpenter, Matthew J; Andrews, Jeannette O; Gray, Kevin M; Alberg, Anthony J; Navarro, Ashley; Friedman, Daniela B; Cummings, K Michael

    2012-12-01

    Pictorial health warning labels on cigarette packaging have been proposed for the U.S., but their potential influences among populations that suffer tobacco-related health disparities are unknown. To evaluate pictorial health warning labels, including moderation of their influences by health literacy and race. From July 2011 to January 2012, field experiments were conducted with 981 adult smokers who were randomized to control (i.e., text-only labels, n=207) and experimental conditions (i.e., pictorial labels, n=774). The experimental condition systematically varied health warning label stimuli by health topic and image type. Linear mixed effects (LME) models estimated the influence of health warning label characteristics and participant characteristics on label ratings. Data were analyzed from January 2012 to April 2012. Compared to text-only warning labels, pictorial warning labels were rated as more personally relevant (5.7 vs 6.8, pinteractions indicated that labels with graphic imagery produced minimal differences in ratings across racial groups and levels of health literacy, whereas other imagery produced greater group differences. Pictorial health warning labels with graphic images have the most-pronounced short-term impacts on adult smokers, including smokers from groups that have in the past been hard to reach. Copyright © 2012 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  12. 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

  13. Open-label, randomized, multicenter, phase III study to evaluate the safety and efficacy of benzoyl peroxide gel in long-term use in patients with acne vulgaris: A secondary publication.

    Science.gov (United States)

    Kawashima, Makoto; Nagare, Toshitaka; Katsuramaki, Tsuneo

    2017-06-01

    An open-label, randomized, multicenter study was conducted to evaluate the safety and efficacy of long-term use of 2.5% and 5% benzoyl peroxide (BPO) gels administrated once daily for 52 weeks to Japanese patients with acne vulgaris. The efficacy of the study drugs was evaluated by counting inflammatory lesions and non-inflammatory lesions. Safety was evaluated based on adverse events, local skin tolerability scores and laboratory test values. In total, 458 subjects were included in the efficacy and safety analyses. The total lesion count, the efficacy end-point, was similarly changed both in the 2.5% and 5% BPO groups over the course of the study. The median rates of reduction from baseline to week 12 were approximately 65%. Thereafter, the counts were maintained at a reduced level without increasing until week 52. The median rates at week 52 were approximately 80%. Similar trends were observed for inflammatory and non-inflammatory lesion counts. Bacteriological evaluation indicated similar distribution of the minimum inhibitory concentration of each of the antibacterial drugs against Propionibacterium acnes between the values at baseline and at week 52, suggesting that long-term use did not result in changes in the drug sensitivity. The incidence of adverse events was 84.0% in the 2.5% BPO group and 87.2% in the 5% BPO group. Many of the adverse events occurred within the first month and were mild or moderate in severity and transient. The results suggest that both 2.5% and 5% BPO gels are effective and safe for long-term treatment of patients with acne vulgaris. © 2017 The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.

  14. The Use of Cervical Auscultation to Predict Oropharyngeal Aspiration in Children: A Randomized Controlled Trial.

    Science.gov (United States)

    Frakking, Thuy T; Chang, Anne B; O'Grady, Kerry-Ann F; David, Michael; Walker-Smith, Katie; Weir, Kelly A

    2016-12-01

    In this study, we aimed to determine if the use of cervical auscultation (CA) as an adjunct to the clinical feeding evaluation (CFE + CA) improves the reliability of predicting oropharyngeal aspiration (abbreviated to aspiration) in children. The design of the study is based on open label, randomized controlled trial with concealed allocation. Results from children (<18 years) randomized to either CFE or CFE + CA were compared to videofluoroscopic swallow study (VFSS), the reference standard data. Aspiration was defined using the Penetration-Aspiration Scale. All assessments were undertaken at a single tertiary pediatric hospital. 155 children referred for a feeding/swallowing assessment were randomized into the CFE n = 83 [38 males; mean age = 34.9 months (SD 34.4)] or CFE + CA n = 72 [43 males; mean age = 39.6 months (SD 39.3)] group. kappa statistic, sensitivity, and specificity values, area under receiver operating curve (aROC). No significant differences between groups were found, although CFE + CA (kappa = 0.41, 95 % CI 0.2-0.62) had higher agreement for aspiration detection by VFSS, compared to the clinical feeding exam alone (kappa = 0.31, 95 % CI 0.10-0.52). Sensitivity was 85 % (95 % CI 62.1-96.8) for CFE + CA and 63.6 % (95 % CI 45.1-79.6) for CFE. aROC was not significantly greater for CFE + CA (0.75, 95 % CI 0.65-0.86) than CFE (0.66, 95 % CI 0.55-0.76) across all age groups. Although using CA as an adjunct to the clinical feeding evaluation improves the sensitivity of predicting aspiration in children, it is not sensitive enough as a diagnostic tool in isolation. Given the serious implications of missing the diagnosis of aspiration, instrumental assessments (e.g., VFSS), remain the preferred standard.

  15. A multicenter, randomized controlled trial of individualized occupational therapy for patients with schizophrenia in Japan.

    Science.gov (United States)

    Shimada, Takeshi; Ohori, Manami; Inagaki, Yusuke; Shimooka, Yuko; Sugimura, Naoya; Ishihara, Ikuyo; Yoshida, Tomotaka; Kobayashi, Masayoshi

    2018-01-01

    The individualized occupational therapy (IOT) program is a psychosocial program that we developed to facilitate proactive participation in treatment and improve cognitive functioning and other outcomes for inpatients with acute schizophrenia. The program consists of motivational interviewing, self-monitoring, individualized visits, handicraft activities, individualized psychoeducation, and discharge planning. This multicenter, open-labeled, blinded-endpoint, randomized controlled trial evaluated the impact of adding IOT to a group OT (GOT) program as usual for outcomes in recently hospitalized patients with schizophrenia in Japanese psychiatric hospitals setting compared with GOT alone. Patients with schizophrenia were randomly assigned to the GOT+IOT group or the GOT alone group. Among 136 randomized patients, 129 were included in the intent-to-treat population: 66 in the GOT+IOT and 63 in the GOT alone groups. Outcomes were administered at baseline and discharge or 3 months following hospitalization including the Brief Assessment of Cognition in Schizophrenia Japanese version (BACS-J), the Schizophrenia Cognition Rating Scale Japanese version, the Social Functioning Scale Japanese version, the Global Assessment of Functioning scale, the Intrinsic Motivation Inventory Japanese version (IMI-J), the Morisky Medication Adherence Scale-8 (MMAS-8), the Positive and Negative Syndrome Scale (PANSS), and the Japanese version of Client Satisfaction Questionnaire-8 (CSQ-8J). Results of linear mixed effects models indicated that the IOT+GOT showed significant improvements in verbal memory (p <0.01), working memory (p = 0.02), verbal fluency (p < 0.01), attention (p < 0.01), and composite score (p < 0.01) on the BACS-J; interest/enjoyment (p < 0.01), value/usefulness (p < 0.01), perceived choice (p < 0.01), and IMI-J total (p < 0.01) on the IMI-J; MMAS-8 score (p < 0.01) compared with the GOT alone. Patients in the GOT+IOT demonstrated significant improvements on the CSQ-8J

  16. Telemedicine Provides Non-Inferior Research Informed Consent for Remote Study Enrollment: A Randomized Controlled Trial

    Science.gov (United States)

    Bobb, Morgan R.; Van Heukelom, Paul G.; Faine, Brett A.; Ahmed, Azeemuddin; Messerly, Jeffrey T.; Bell, Gregory; Harland, Karisa K.; Simon, Christian; Mohr, Nicholas M.

    2016-01-01

    Objective Telemedicine networks are beginning to provide an avenue for conducting emergency medicine research, but using telemedicine to recruit participants for clinical trials has not been validated. The goal of this consent study is to determine whether patient comprehension of telemedicine-enabled research informed consent is non-inferior to standard face-to-face research informed consent. Methods A prospective, open-label randomized controlled trial was performed in a 60,000-visit Midwestern academic Emergency Department (ED) to test whether telemedicine-enabled research informed consent provided non-inferior comprehension compared with standard consent. This study was conducted as part of a parent clinical trial evaluating the effectiveness of oral chlorhexidine gluconate 0.12% in preventing hospital-acquired pneumonia among adult ED patients with expected hospital admission. Prior to being recruited into the study, potential participants were randomized in a 1:1 allocation ratio to consent by telemedicine versus standard face-to-face consent. Telemedicine connectivity was provided using a commercially available interface (REACH platform, Vidyo Inc., Hackensack, NJ) to an emergency physician located in another part of the ED. Comprehension of research consent (primary outcome) was measured using the modified Quality of Informed Consent (QuIC) instrument, a validated tool for measuring research informed consent comprehension. Parent trial accrual rate and qualitative survey data were secondary outcomes. Results One-hundred thirty-one patients were randomized (n = 64, telemedicine), and 101 QuIC surveys were completed. Comprehension of research informed consent using telemedicine was not inferior to face-to-face consent (QuIC scores 74.4 ± 8.1 vs. 74.4 ± 6.9 on a 100-point scale, p = 0.999). Subjective understanding of consent (p=0.194) and parent trial study accrual rates (56% vs. 69%, p = 0.142) were similar. Conclusion Telemedicine is non-inferior to face

  17. Different effect of psyllium and guar dietary supplementation on blood pressure control in hypertensive overweight patients: a six-month, randomized clinical trial.

    Science.gov (United States)

    Cicero, Arrigo F G; Derosa, Giuseppe; Manca, Marco; Bove, Marilisa; Borghi, Claudio; Gaddi, Antonio V

    2007-08-01

    In the setting of a six-month, open-label clinical trial, 141 consecutively enrolled, hypertensive, overweight patients were randomized to the oral ingestion of psyllium powder or guar gum 3.5 gr t.i.d., to be taken 20 min before the main two meals, or to standard diet. Both fibers improved significantly BMI, FPG, FPI, HOMA Index, HbA1c, LDL-C, and ApoB. Psyllium supplementation only exerted a significant improvement in plasma TG concentration, in SBP and DBP. In our study, six-month supplementation with psyllium fiber, but not with guar fiber nor standard diet, appears to significantly reduce both SBP and DBP in hypertensive overweight subjects.

  18. Current good manufacturing practice in manufacturing, processing, packing, or holding of drugs; revision of certain labeling controls. Final rule.

    Science.gov (United States)

    2012-03-20

    The Food and Drug Administration (FDA) is amending the packaging and labeling control provisions of the current good manufacturing practice (CGMP) regulations for human and veterinary drug products by limiting the application of special control procedures for the use of cut labeling to immediate container labels, individual unit cartons, or multiunit cartons containing immediate containers that are not packaged in individual unit cartons. FDA is also permitting the use of any automated technique, including differentiation by labeling size and shape, that physically prevents incorrect labeling from being processed by labeling and packaging equipment when cut labeling is used. This action is intended to protect consumers from labeling errors more likely to cause adverse health consequences, while eliminating the regulatory burden of applying the rule to labeling unlikely to reach or adversely affect consumers. This action is also intended to permit manufacturers to use a broader range of error prevention and labeling control techniques than permitted by current CGMPs.

  19. Intervention randomized controlled trials involving wrist and shoulder arthroscopy: a systematic review

    Science.gov (United States)

    2014-01-01

    Background Although arthroscopy of upper extremity joints was initially a diagnostic tool, it is increasingly used for therapeutic interventions. Randomized controlled trials (RCTs) are considered the gold standard for assessing treatment efficacy. We aimed to review the literature for intervention RCTs involving wrist and shoulder arthroscopy. Methods We performed a systematic review for RCTs in which at least one arm was an intervention performed through wrist arthroscopy or shoulder arthroscopy. PubMed and Cochrane Library databases were searched up to December 2012. Two researchers reviewed each article and recorded the condition treated, randomization method, number of randomized participants, time of randomization, outcomes measures, blinding, and description of dropouts and withdrawals. We used the modified Jadad scale that considers the randomization method, blinding, and dropouts/withdrawals; score 0 (lowest quality) to 5 (highest quality). The scores for the wrist and shoulder RCTs were compared with the Mann–Whitney test. Results The first references to both wrist and shoulder arthroscopy appeared in the late 1970s. The search found 4 wrist arthroscopy intervention RCTs (Kienböck’s disease, dorsal wrist ganglia, volar wrist ganglia, and distal radius fracture; first 3 compared arthroscopic with open surgery). The median number of participants was 45. The search found 50 shoulder arthroscopy intervention RCTs (rotator cuff tears 22, instability 14, impingement 9, and other conditions 5). Of these, 31 compared different arthroscopic treatments, 12 compared arthroscopic with open treatment, and 7 compared arthroscopic with nonoperative treatment. The median number of participants was 60. The median modified Jadad score for the wrist RCTs was 0.5 (range 0–1) and for the shoulder RCTs 3.0 (range 0–5) (p = 0.012). Conclusion Despite the increasing use of wrist arthroscopy in the treatment of various wrist disorders the efficacy of arthroscopically

  20. Effects of an Oral Elemental Nutritional Supplement on Post-gastrectomy Body Weight Loss in Gastric Cancer Patients: A Randomized Controlled Clinical Trial.

    Science.gov (United States)

    Imamura, Hiroshi; Nishikawa, Kazuhiro; Kishi, Kentaro; Inoue, Kentaro; Matsuyama, Jin; Akamaru, Yusuke; Kimura, Yutaka; Tamura, Shigeyuki; Kawabata, Ryohei; Kawada, Junji; Fujiwara, Yoshiyuki; Kawase, Tomono; Fukui, Junichi; Takagi, Mari; Takeno, Atsushi; Shimokawa, Toshio

    2016-09-01

    Post-gastrectomy weight loss is associated with deterioration in quality of life, and influences the long-term prognosis of gastric cancer patients. We conducted a prospective, randomized controlled, open-label study to examine whether an oral elemental diet (Elental(®), Ajinomoto Pharmaceuticals, Tokyo, Japan; hereafter referred to as ED) prevents postoperative weight loss in post-gastrectomy patients. Patients were randomly divided to receive the ED or control diet. The ED group received 300 kcal of ED plus their regular diet for 6-8 weeks after surgery, starting from the day the patient started a soft rice or equivalent diet after surgery, while the control group received the regular diet alone. The primary endpoint was the percentage of body weight loss (%BWL) from the presurgical body weight to that at 6-8 weeks after surgery. Secondary endpoints were dietary adherence, nutrition-related blood parameters, and adverse events. This study included 112 patients in eight hospitals. The mean treatment compliance rate in the ED group was 68.7 ± 30.4 % (median 81.2 %). The %BWL was significantly different between the ED and control groups (4.86 ± 3.72 vs. 6.60 ± 4.90 %, respectively; p = 0.047). In patients who underwent total gastrectomy, the %BWL was significantly different between the two groups (5.03 ± 3.65 vs. 9.13 ± 5.43 %, respectively; p = 0.012). In multivariate analysis, ED treatment, surgery type, and preoperative performance status were independently associated with %BWL. No significant differences were observed in the other clinical variables. ED supplementation reduced postoperative weight loss in gastric cancer patients undergoing gastrectomy.

  1. A Monte Carlo study of adsorption of random copolymers on random surfaces

    CERN Document Server

    Moghaddam, M S

    2003-01-01

    We study the adsorption problem of a random copolymer on a random surface in which a self-avoiding walk in three dimensions interacts with a plane defining a half-space to which the walk is confined. Each vertex of the walk is randomly labelled A with probability p sub p or B with probability 1 - p sub p , and only vertices labelled A are attracted to the surface plane. Each lattice site on the plane is also labelled either A with probability p sub s or B with probability 1 - p sub s , and only lattice sites labelled A interact with the walk. We study two variations of this model: in the first case the A-vertices of the walk interact only with the A-sites on the surface. In the second case the constraint of selective binding is removed; that is, any contact between the walk and the surface that involves an A-labelling, either from the surface or from the walk, is counted as a visit to the surface. The system is quenched in both cases, i.e. the labellings of the walk and of the surface are fixed as thermodynam...

  2. Labelling fashion magazine advertisements: Effectiveness of different label formats on social comparison and body dissatisfaction.

    Science.gov (United States)

    Tiggemann, Marika; Brown, Zoe

    2018-06-01

    The experiment investigated the impact on women's body dissatisfaction of different forms of label added to fashion magazine advertisements. Participants were 340 female undergraduate students who viewed 15 fashion advertisements containing a thin and attractive model. They were randomly allocated to one of five label conditions: no label, generic disclaimer label (indicating image had been digitally altered), consequence label (indicating that viewing images might make women feel bad about themselves), informational label (indicating the model in the advertisement was underweight), or a graphic label (picture of a paint brush). Although exposure to the fashion advertisements resulted in increased body dissatisfaction, there was no significant effect of label type on body dissatisfaction; no form of label demonstrated any ameliorating effect. In addition, the consequence and informational labels resulted in increased perceived realism and state appearance comparison. Yet more extensive research is required before the effective implementation of any form of label. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. Affect school and script analysis versus basic body awareness therapy in the treatment of psychological symptoms in patients with diabetes and high HbA1c concentrations: two study protocols for two randomized controlled trials.

    Science.gov (United States)

    Melin, Eva O; Svensson, Ralph; Gustavsson, Sven-Åke; Winberg, Agneta; Denward-Olah, Ewa; Landin-Olsson, Mona; Thulesius, Hans O

    2016-04-27

    Depression is linked with alexithymia, anxiety, high HbA1c concentrations, disturbances of cortisol secretion, increased prevalence of diabetes complications and all-cause mortality. The psycho-educational method 'affect school with script analysis' and the mind-body therapy 'basic body awareness treatment' will be trialled in patients with diabetes, high HbA1c concentrations and psychological symptoms. The primary outcome measure is change in symptoms of depression. Secondary outcome measures are changes in HbA1c concentrations, midnight salivary cortisol concentration, symptoms of alexithymia, anxiety, self-image measures, use of antidepressants, incidence of diabetes complications and mortality. Two studies will be performed. Study I is an open-labeled parallel-group study with a two-arm randomized controlled trial design. Patients are randomized to either affect school with script analysis or to basic body awareness treatment. According to power calculations, 64 persons are required in each intervention arm at the last follow-up session. Patients with type 1 or type 2 diabetes were recruited from one hospital diabetes outpatient clinic in 2009. The trial will be completed in 2016. Study II is a multicentre open-labeled parallel-group three-arm randomized controlled trial. Patients will be randomized to affect school with script analysis, to basic body awareness treatment, or to treatment as usual. Power calculations show that 70 persons are required in each arm at the last follow-up session. Patients with type 2 diabetes will be recruited from primary care. This study will start in 2016 and finish in 2023. For both studies, the inclusion criteria are: HbA1c concentration ≥62.5 mmol/mol; depression, alexithymia, anxiety or a negative self-image; age 18-59 years; and diabetes duration ≥1 year. The exclusion criteria are pregnancy, severe comorbidities, cognitive deficiencies or inadequate Swedish. Depression, anxiety, alexithymia and self-image are assessed

  4. PREDOMOS study, impact of a social intervention program for socially isolated elderly cancer patients: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Crétel-Durand, Elodie; Nouguerède, Emilie; Le Caer, Hervé; Rousseau, Frédérique; Retornaz, Frédérique; Guillem, Olivier; Couderc, Anne-Laure; Greillier, Laurent; Norguet, Emmanuelle; Cécile, Maud; Boulahssass, Rabia; Le Caer, Francoise; Tournier, Sandrine; Butaud, Chantal; Guillet, Pierre; Nahon, Sophie; Poudens, Laure; Kirscher, Sylvie; Loubière, Sandrine; Diaz, Nadine; Dhorne, Jean; Auquier, Pascal; Baumstarck, Karine

    2017-04-12

    Cancer incidence and social isolation increase along with advanced age, and social isolation potentiates the relative risk of death by cancer. Once spotted, social isolation can be averted with the intervention of a multidisciplinary team. Techniques of automation and remote assistance have already demonstrated their positive impact on falls prevention and quality of life (QoL), though little is known about their impact on socially isolated elderly patients supported for cancer. The primary objective of the PREDOMOS study is to evaluate the impact of establishing a Program of Social intervention associated with techniques of Domotic and Remote assistance (PS-DR) on the improvement of QoL of elderly isolated patients, treated for locally advanced or metastatic cancer. The secondary objectives include treatment failure, tolerance, survival, and autonomy. This trial is a multicenter, prospective, randomized, placebo-controlled, open-label, two-parallel group study. The setting is 10 French oncogeriatric centers. Inclusion criteria are patients aged at least 70 years with a social isolation risk and a histological diagnosis of cancer, locally advanced or metastatic disease. The groups are (1) the control group, receiving usual care; (2) the experimental group, receiving usual care associating with monthly social assistance, domotic, and remote assistance. Participants are randomized in a 1:1 allocation ratio. Evaluation times involve inclusion (randomization) and follow-up (12 months). The primary endpoint is QoL at 3 months (via European Organization for Research and Treatment of Cancer (EORTC) QLQ C30); secondary endpoints are social isolation, time to treatment failure, toxicity, dose response-intensity, survival, autonomy, and QoL at 6 months. For the sample size, 320 individuals are required to obtain 90% power to detect a 10-point difference (standard deviation 25) in QoL score between the two groups (20% loss to follow-up patients expected). The randomized

  5. [Preliminary results of an open-label observational study evaluating the efficacy and safety of Prolia used in women with postmenopausal osteoporosis].

    Science.gov (United States)

    Ershova, O B; Lesniak, O M; Belova, K Iu; Nazarova, A V; Manovitskaia, A V; Musaeva, T M; Musraev, R M; Nurlygaianov, R Z; Rozhinskaia, L Ia; Skripnikova, I A; Toroptsova, N V

    2014-01-01

    To evaluate the efficacy and safety of Denosumab (Prolia), a first-line osteoporosis (OP) medication that is a fully human monoclonal antibody to the receptor activator of nuclear factor xB ligand (RANKL), within an open-label observational study. Patients aged 50 years or older with postmenopausal OP, who were treated with Prolia in clinical practice, were examined. The concentrations of the bone resorption (BR) marker of C-terminal telopeptide and other laboratory indicators (total serum calcium, total alkaline phosphatase, and creatinine) were measured following 3 months. Adverse drug reactions were recorded. Three months after initiation of the investigation, there was a significant decrease in the BR marker C-terminal telopeptide (by 89%; p<0.0001). There were rare adverse reactions: hypocalcemia in 3 (5.9%) patients, arthralgias in 2 (3.9%), and eczema in 1 (1.9%). There were neither serious adverse events nor study withdrawal cases. The preliminary results of the open-label study of Prolia in postmenopausal OP suggest that the significantly lower BR activity determines the efficacy of this drug and its high safety.

  6. OpenLMD, multimodal monitoring and control of LMD processing

    Science.gov (United States)

    Rodríguez-Araújo, Jorge; García-Díaz, Antón

    2017-02-01

    This paper presents OpenLMD, a novel open-source solution for on-line multimodal monitoring of Laser Metal Deposition (LMD). The solution is also applicable to a wider range of laser-based applications that require on-line control (e.g. laser welding). OpenLMD is a middleware that enables the orchestration and virtualization of a LMD robot cell, using several open-source frameworks (e.g. ROS, OpenCV, PCL). The solution also allows reconfiguration by easy integration of multiple sensors and processing equipment. As a result, OpenLMD delivers significant advantages over existing monitoring and control approaches, such as improved scalability, and multimodal monitoring and data sharing capabilities.

  7. Phase II open label study of valproic acid in spinal muscular atrophy.

    Directory of Open Access Journals (Sweden)

    Kathryn J Swoboda

    Full Text Available Preliminary in vitro and in vivo studies with valproic acid (VPA in cell lines and patients with spinal muscular atrophy (SMA demonstrate increased expression of SMN, supporting the possibility of therapeutic benefit. We performed an open label trial of VPA in 42 subjects with SMA to assess safety and explore potential outcome measures to help guide design of future controlled clinical trials. Subjects included 2 SMA type I ages 2-3 years, 29 SMA type II ages 2-14 years and 11 type III ages 2-31 years, recruited from a natural history study. VPA was well-tolerated and without evident hepatotoxicity. Carnitine depletion was frequent and temporally associated with increased weakness in two subjects. Exploratory outcome measures included assessment of gross motor function via the modified Hammersmith Functional Motor Scale (MHFMS, electrophysiologic measures of innervation including maximum ulnar compound muscle action potential (CMAP amplitudes and motor unit number estimation (MUNE, body composition and bone density via dual-energy X-ray absorptiometry (DEXA, and quantitative blood SMN mRNA levels. Clear decline in motor function occurred in several subjects in association with weight gain; mean fat mass increased without a corresponding increase in lean mass. We observed an increased mean score on the MHFMS scale in 27 subjects with SMA type II (p

  8. Effects of an oral contraceptive (norgestimate/ethinyl estradiol) on bone mineral density in women with hypothalamic amenorrhea and osteopenia: an open-label extension of a double-blind, placebo-controlled study.

    Science.gov (United States)

    Warren, Michelle P; Miller, K K; Olson, W H; Grinspoon, S K; Friedman, A J

    2005-09-01

    The effects of long-term triphasic oral contraceptive administration on bone mineral density (BMD) were investigated in premenopausal women with hypothalamic amenorrhea (HA) and osteopenia. After completing three 28-day cycles in the double-blind phase of a placebo-controlled trial, women (mean age, 26.7 years) who received norgestimate 180-250 microg/ethinyl estradiol 35 microg (NGM/EE, n = 15) or placebo (n = 12) in the double-blind phase were to receive open-label NGM/EE for 10 additional cycles. For subjects completing > or =10 NGM/EE treatment cycles, mean posteroanterior total lumbar spine BMD (L1-L4) increased from 0.881+/-0.0624 g/cm2 at baseline (last visit prior to NGM/EE) to 0.894+/-0.0654 g/cm2 at final visit (p = .043); no significant changes in hip BMD occurred. Decreases in N-telopeptide, osteocalcin, procollagen type I propeptide and bone-specific alkaline phosphatase levels indicated effects on bone metabolism. Long-term administration of triphasic NGM/EE to osteopenic women with HA may increase total lumbar spine BMD.

  9. 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.

  10. 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

  11. Randomized controlled trial of video self-modeling following speech restructuring treatment for stuttering.

    Science.gov (United States)

    Cream, Angela; O'Brian, Sue; Jones, Mark; Block, Susan; Harrison, Elisabeth; Lincoln, Michelle; Hewat, Sally; Packman, Ann; Menzies, Ross; Onslow, Mark

    2010-08-01

    In this study, the authors investigated the efficacy of video self-modeling (VSM) following speech restructuring treatment to improve the maintenance of treatment effects. The design was an open-plan, parallel-group, randomized controlled trial. Participants were 89 adults and adolescents who undertook intensive speech restructuring treatment. Post treatment, participants were randomly assigned to 2 trial arms: standard maintenance and standard maintenance plus VSM. Participants in the latter arm viewed stutter-free videos of themselves each day for 1 month. The addition of VSM did not improve speech outcomes, as measured by percent syllables stuttered, at either 1 or 6 months postrandomization. However, at the latter assessment, self-rating of worst stuttering severity by the VSM group was 10% better than that of the control group, and satisfaction with speech fluency was 20% better. Quality of life was also better for the VSM group, which was mildly to moderately impaired compared with moderate impairment in the control group. VSM intervention after treatment was associated with improvements in self-reported outcomes. The clinical implications of this finding are discussed.

  12. 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.

    Science.gov (United States)

    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

  13. Preincisional analgesia with subcutaneous administration of tramadol reduces postoperative pain in patients after open urologic surgeries: a randomized, double-blind, placebo-controlled study

    International Nuclear Information System (INIS)

    Safavi, M.; Honarmand, A.; Ghaedi, F.

    2012-01-01

    Objective: Blockade of parietal nociceptive afferent nerves by wound infiltration with tramadol may be advantageous in the management of postoperative pain. The purpose of the present study was to assess the efficacy of preincisional subcutaneous administration of two doses of tramadol on postoperative pain relief after open urologic surgeries. Methodology: Ninety-six patients scheduled for open urologic surgeries were enrolled in this randomized, double-blind, placebo-controlled study. Patients were divided into three groups of 32 subjects each, and they received subcutaneous administrations of tramadol at 1 mg.kg/sup -1/ (Group T1) or 2 mg.kg/sup -1 (Group T2) or subcutaneous administrations of 10 mL of normal saline (Group C) before undergoing the surgeries. Visual analog scale (VAS) scores and analgesic use were monitored for 24 h after the operation. Results: VAS scores were significantly lower at 15, 30, and 60 min after arrival at the post anesthesia care unit in Group T2 compared with Group T1 and Group C (P < 0.05). Postoperative VAS scores were significantly lower at 4, 8, 16 and 24 h postoperatively in Group T2 compared with Group T1 and Group C. There were no significant differences between Group T1 and Group C on VAS scores at any time point. The time to first rescue analgesia in the postoperative period was significantly lower in Group T2 compared with Group T1 and Group C. The need for postoperative analgesia was significantly lower in Group T2 compared with Group T1 and Group C. Conclusion: Preincisional subcutaneous administration of tramadol at 2 mg.kg/sup -1/ provides effective analgesia during the first 24 hour after open urologic surgeries and does not produce significant side effects. (author)

  14. Randomized Controlled Trial of Early Versus Delayed Statin Therapy in Patients With Acute Ischemic Stroke: ASSORT Trial (Administration of Statin on Acute Ischemic Stroke Patient).

    Science.gov (United States)

    Yoshimura, Shinichi; Uchida, Kazutaka; Daimon, Takashi; Takashima, Ryuzo; Kimura, Kazuhiro; Morimoto, Takeshi

    2017-11-01

    Several studies suggested that statins during hospitalization were associated with better disability outcomes in patients with acute ischemic stroke, but only 1 small randomized trial is available. We conducted a multicenter, open-label, randomized controlled trial in patients with acute ischemic strokes in 11 hospitals in Japan. Patients with acute ischemic stroke and dyslipidemia randomly received statins within 24 hours after admission in the early group or on the seventh day in the delayed group, in a 1:1 ratio. Statins were administered for 12 weeks. The primary outcome was patient disability assessed by modified Rankin Scale at 90 days. A total of 257 patients were randomized and analyzed (early 131, delayed 126). At 90 days, modified Rankin Scale score distribution did not differ between groups ( P =0.68), and the adjusted common odds ratio of the early statin group was 0.84 (95% confidence interval, 0.53-1.3; P =0.46) compared with the delayed statin group. There were 3 deaths at 90 days (2 in the early group, 1 in the delayed group) because of malignancy. Ischemic stroke recurred in 9 patients (6.9%) in the early group and 5 patients (4.0%) in the delayed group. The safety profile was similar between groups. Our randomized trial involving patients with acute ischemic stroke and dyslipidemia did not show any superiority of early statin therapy within 24 hours of admission compared with delayed statin therapy 7 days after admission to alleviate the degree of disability at 90 days after onset. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02549846. © 2017 American Heart Association, Inc.

  15. Invitation cards during pregnancy enhance male partner involvement in prevention of mother to child transmission (PMTCT of human immunodeficiency virus (HIV in Blantyre, Malawi: a randomized controlled open label trial.

    Directory of Open Access Journals (Sweden)

    Alinane Linda Nyondo

    Full Text Available Male involvement (MI is vital for the uptake of Prevention of Mother to Child Transmission (PMTCT of Human Immunodeficiency Virus (HIV interventions. Partner notification (PN is among the strategies identified for MI in PMTCT services. The purpose of this randomized controlled trial was to evaluate the efficacy of an invitation card to the male partners as a strategy for MI in PMTCT services by comparing the proportion of pregnant women that were accompanied by their partners between the intervention and the non-intervention study groups.Pregnant women attending antenatal care without a male partner at South Lunzu and Mpemba health centres in Blantyre, Malawi, were enrolled in the study from June to December 2013. In an intention-to-treat analysis, we compared all participants that were randomized in the invitation card group with the standard of care (SoC group. Risk ratios (RR with 95% confidence intervals (CI were computed to assess the efficacy of the invitation card.Of the 462 randomized women, 65/230 (28.26% of the women in the invitation card group reported to the antenatal care clinic with their partners compared to 44/232 (18.97% women in the SoC group. In an unadjusted intention-to-treat analysis women in the invitation card group were 50% more likely to be accompanied by their male partners than those in the SoC group RR: 1.49 (95% CI: 1.06-2.09; p = 0.02. Our random effects analysis showed that there was no clustering by site of recruitment with an inter cluster correlation coefficient (ICC of 1.98 x 10(-3, (95% CI: 1.78 x10(-7 - 0.96 x 10(-1; p =0.403.An invitation card significantly increased the proportion of women who were accompanied by their male partners for the PMTCT services. An invitation card is a feasible strategy for MI in PMTCT.

  16. The effect of reflexotherapy and massage therapy on vital signs and stress before coronary angiography: An open-label clinical trial

    Directory of Open Access Journals (Sweden)

    Ali Khaledifar

    2017-05-01

    Full Text Available BACKGROUND: Complementary medicine interventions are now successfully used to reduce stress as well as to stabilize hemodynamic indices within different procedures. The present study aimed to examine the effect of massage therapy and reflexotherapy on reducing stress in patients before coronary angiography. METHODS: In this open-label clinical trial, 75 consecutive patients who were candidate for coronary angiography were randomly assigned to receive reflexotherapy (n = 25, or massage therapy (n = 25, or routine care (n = 25 before angiography. The Spielberger State-Trait Anxiety Inventory was used to determine the stress level of patients before and after interventions and vital signs were also measured. RESULTS: Improvement in diastolic blood pressure, heart rate, and respiratory rate was shown in the reflexotherapy group, and similar effects were observed following other interventions including massage therapy and routine resting program. In subjects who received reflexotherapy the level of stress decreased slightly compared with the other two groups. However, following interventions the level of stress in reflexotherapy group was shown to be lower than other study groups. CONCLUSION: Reflexotherapy before coronary angiography can help to stabilize vital sign as well as reduce the level of stress. The effect of massage therapy was limited to reducing stress.   

  17. Low salt and low calorie diet does not reduce more body fat than same calorie diet: a randomized controlled study.

    Science.gov (United States)

    Kang, Hye Jin; Jun, Dae Won; Lee, Seung Min; Jang, Eun Chul; Cho, Yong Kyun

    2018-02-02

    Recent several observational studies have reported that high salt intake is associated with obesity. But it is unclear whether salt intake itself induce obesity or low salt diet can reduce body fat mass. We investigated whether a low salt diet can reduce body weight and fat amount. The randomized, open-label pilot trial was conducted at a single institution. A total of 85 obese people were enrolled. All participants were served meals three times a day, and provided either a low salt diet or control diet with same calorie. Visceral fat was measured with abdominal computer tomography, while body fat mass and total body water was measured with bio-impedance. Reductions in body weight (-6.3% vs. -5.0%, p = 0.05) and BMI (-6.6% vs. -5.1%, p = 0.03) were greater in the low salt group than in the control group. Extracellular water and total body water were significantly reduced in the low salt group compared to the control group. However, changes in body fat mass, visceral fat area, and skeletal muscle mass did not differ between the two groups. Changes in lipid profile, fasting glucose, and HOMA-IR did not differ between the two groups. A two-month low salt diet was accompanied by reduction of body mass index. However, the observed decrease of body weight was caused by reduction of total body water, not by reduction of body fat mass or visceral fat mass.

  18. Control landscapes for observable preparation with open quantum systems

    International Nuclear Information System (INIS)

    Wu Rebing; Pechen, Alexander; Rabitz, Herschel; Hsieh, Michael; Tsou, Benjamin

    2008-01-01

    A quantum control landscape is defined as the observable as a function(al) of the system control variables. Such landscapes were introduced to provide a basis to understand the increasing number of successful experiments controlling quantum dynamics phenomena. This paper extends the concept to encompass the broader context of the environment having an influence. For the case that the open system dynamics are fully controllable, it is shown that the control landscape for open systems can be lifted to the analysis of an equivalent auxiliary landscape of a closed composite system that contains the environmental interactions. This inherent connection can be analyzed to provide relevant information about the topology of the original open system landscape. Application to the optimization of an observable expectation value reveals the same landscape simplicity observed in former studies on closed systems. In particular, no false suboptimal traps exist in the system control landscape when seeking to optimize an observable, even in the presence of complex environments. Moreover, a quantitative study of the control landscape of a system interacting with a thermal environment shows that the enhanced controllability attainable with open dynamics significantly broadens the range of the achievable observable values over the control landscape

  19. Cannabis (medical marijuana) treatment for motor and non-motor symptoms of Parkinson disease: an open-label observational study.

    Science.gov (United States)

    Lotan, Itay; Treves, Therese A; Roditi, Yaniv; Djaldetti, Ruth

    2014-01-01

    The use of cannabis as a therapeutic agent for various medical conditions has been well documented. However, clinical trials in patients with Parkinson disease (PD) have yielded conflicting results. The aim of the present open-label observational study was to assess the clinical effect of cannabis on motor and non-motor symptoms of PD. Twenty-two patients with PD attending the motor disorder clinic of a tertiary medical center in 2011 to 2012 were evaluated at baseline and 30 minutes after smoking cannabis using the following battery: Unified Parkinson Disease Rating Scale, visual analog scale, present pain intensity scale, Short-Form McGill Pain Questionnaire, as well as Medical Cannabis Survey National Drug and Alcohol Research Center Questionnaire. Mean (SD) total score on the motor Unified Parkinson Disease Rating Scale score improved significantly from 33.1 (13.8) at baseline to 23.2 (10.5) after cannabis consumption (t = 5.9; P effects of the drug were observed. The study suggests that cannabis might have a place in the therapeutic armamentarium of PD. Larger, controlled studies are needed to verify the results.

  20. Randomized controlled psychotherapy trials in eating disorders: Improving their conduct, interpretation and usefulness.

    Science.gov (United States)

    Wade, Tracey D; Johnson, Catherine; Byrne, Susan M

    2018-04-25

    While randomized controlled trials (RCTs) inform the efficacy and effectiveness of treatments, we need to understand that even RCTs can be associated with sub-optimal execution. This is of special pertinence to eating disorders given the majority of treatment studies involving cognitive behaviour therapy are of poor quality with respect to managing risk of bias adequately. The current paper outlines the components of a good RCT for psychotherapy, and examines ways to improve the conduct, interpretation, and usefulness of RCTs. This includes managing reporting bias, recognizing the limits of randomization, applicability, and ethical considerations. We highlight a number of strategies for future research, including issues related to utilizing a variety of designs to examine treatment outcomes, integrity, openness and reproducibility. © 2018 Wiley Periodicals, Inc.

  1. 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.

    Science.gov (United States)

    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

  2. Whey Protein Supplementation Enhances Body Fat and Weight Loss in Women Long After Bariatric Surgery: a Randomized Controlled Trial.

    Science.gov (United States)

    Lopes Gomes, Daniela; Moehlecke, Milene; Lopes da Silva, Fernanda Bassan; Dutra, Eliane Said; D'Agord Schaan, Beatriz; Baiocchi de Carvalho, Kenia Mara

    2017-02-01

    The ideal nutritional approach for weight regain after bariatric surgery remains unclear. The objective of this study is to assess the effect of whey protein supplementation on weight loss and body composition of women who regained weight 24 or more months after bariatric surgery. This is a 16-week open-label, parallel-group, randomized controlled trial of women who regained at least 5 % of their lowest postoperative weight after a Roux-en-Y gastric bypass (RYGB). A total of 34 participants were treated with hypocaloric diet and randomized (1:1) to receive or not supplementation with whey protein, 0.5 g/kg of the ideal body weight. The primary outcomes were changes in body weight, fat free mass (FFM), and fat mass (FM), evaluated by tetrapolar bioelectrical impedance analysis (BIA). Secondary outcomes included resting energy expenditure, blood glucose, lipids, adiponectin, interleukin 6 (IL-6), and cholecystokinin levels. Statistical analyses included generalized estimating equations adjusted for age and physical activity. Fifteen patients in each group were evaluated: mean age was 45 ± 11 years, body mass index (BMI) was 35.7 ± 5.2 kg/m 2 , and time since surgery was 69 ± 23 months. Protein intake during follow-up increased by approximately 75 % in the intervention group (p = 0.01). The intervention group presented more body weight loss (1.86 kg, p = 0.017), accounted for FM loss (2.78, p = 0.021) and no change in FFM, as compared to controls (gain of 0.42 kg of body weight and 0.6 kg of FM). No differences in secondary outcomes were observed between groups. Whey protein supplementation promoted body weight and FM loss in women with long-term weight regain following RYGB.

  3. Group Cognitive Behavioural Therapy and Group Recreational Activity for Adults with Autism Spectrum Disorders: A Preliminary Randomized Controlled Trial

    Science.gov (United States)

    Hesselmark, Eva; Plenty, Stephanie; Bejerot, Susanne

    2014-01-01

    Although adults with autism spectrum disorder are an increasingly identified patient population, few treatment options are available. This "preliminary" randomized controlled open trial with a parallel design developed two group interventions for adults with autism spectrum disorders and intelligence within the normal range: cognitive…

  4. Lifestyle intervention using Internet of Things (IoT) for the elderly: A study protocol for a randomized control trial (the BEST-LIFE study).

    Science.gov (United States)

    Kato, Sawako; Ando, Masahiko; Kondo, Takaaki; Yoshida, Yasuko; Honda, Hiroyuki; Maruyama, Shoichi

    2018-05-01

    Modification of lifestyle habits, including diet and physical activity, is essential for the prevention and control of type 2 diabetes mellitus (T2DM) in elderly patients. However, individualized treatment is more critical for the elderly than for general patients. This study aimed to determine lifestyle interventions that resulted in lowering hemoglobin A 1c (HbA 1c ) in Japanese pre- and early diabetic elderly subjects. The BEST-LIFE trial is an ongoing, open-label, 6-month, randomized (1:1) parallel group trial. Subjects with HbA 1c of ≥5.6%-randomly assigned to the intervention or control group -use wearable monitoring devices loaded with Internet of things (IoT) systems that aids them with self-management and obtaining monthly remote health guidance from a public health nurse. The primary outcome is changes in HbA 1c after a 6-month intervention relative to the baseline values. The secondary outcome is the change of behavior modification stages. The background, rationale, and study design of this trial are also presented. One hundred forty-five subjects have already been enrolled in this lifestyle intervention program, which will end in 2019. The BEST-LIFE trial will provide new evidence regarding the effectiveness and safety of our program on lowering HbA 1c in elderly subjects with T2DM. It will also investigate whether information communication technology tools and monitoring devices loaded with IoT can support health care in elderly subjects. The trial registration number is UMIN-CTR: UMIN 000023356.

  5. Direct labeling of doxorubicin with technetium-99m. Its optimization, characterization and quality control

    International Nuclear Information System (INIS)

    Rizvi, F.A.; Bokhari, T.H.; Roohi, S.; Mushtaq, A.

    2012-01-01

    Doxorubicin (DOX) is an anthracycline antineoplastic and one of the most potent and widely used drugs in clinical oncology. It is used in the treatment of a wide variety of cancers. The aim of this study was the direct labeling of DOX with 99m Tc; its optimization, characterization and quality control of the radiolabeled DOX. Labeling efficiency was determined by paper chromatography. More than 92% labeling was obtained at pH 6-7, 10-12 μg stannous chloride and 200 μg of DOX. The stability of 99m Tc-DOX was studied up to 5 h. All the experiments were performed at room temperature (25 ± 2 deg C). The characterization of the labeling compound was performed by HPLC and electrophoresis. Electrophoresis indicates that labeled DOX has no charge and HPLC shows single specie of labeled compound. (author)

  6. 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.

  7. Minocycline treatment in acute stroke: an open-label, evaluator-blinded study.

    Science.gov (United States)

    Lampl, Y; Boaz, M; Gilad, R; Lorberboym, M; Dabby, R; Rapoport, A; Anca-Hershkowitz, M; Sadeh, M

    2007-10-02

    Ischemic animal model studies have shown a neuroprotective effect of minocycline. To analyze the effect of minocycline treatment in human acute ischemic stroke. We performed an open-label, evaluator-blinded study. Minocycline at a dosage of 200 mg was administered orally for 5 days. The therapeutic window of time was 6 to 24 hours after onset of stroke. Data from NIH Stroke Scale (NIHSS), modified Rankin Scale (mRS), and Barthel Index (BI) were evaluated. The primary objective was to compare changes from baseline to day 90 in NIHSS in the minocycline group vs placebo. One hundred fifty-two patients were included in the study. Seventy-four patients received minocycline treatment, and 77 received placebo. NIHSS and mRS were significantly lower and BI scores were significantly higher in minocycline-treated patients. This pattern was already apparent on day 7 and day 30 of follow-up. Deaths, myocardial infarctions, recurrent strokes, and hemorrhagic transformations during follow-up did not differ by treatment group. Patients with acute stroke had significantly better outcome with minocycline treatment compared with placebo. The findings suggest a potential benefit of minocycline in acute ischemic stroke.

  8. Phase 2 Randomized Controlled Trial of Radiation Therapy Plus Concurrent Interferon-Alpha and Retinoic Acid Versus Cisplatin for Stage III Cervical Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Basu, Partha, E-mail: BasuP@iarc.fr [Screening Group, Early Detection and Prevention Section, International Agency for Research on Cancer, Lyon (France); Jenson, Alfred Bennett [James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky (United States); Majhi, Tapas; Choudhury, Prabir [Department of Radiation Oncology, Chittaranjan National Cancer Institute, Kolkata (India); Mandal, Ranajit; Banerjee, Dipanwita [Department of Gynecological Oncology, Chittaranjan National Cancer Institute, Kolkata (India); Biswas, Jaydip [Department of Surgical Oncology, Chittaranjan National Cancer Institute, Kolkata (India); Pan, Jianmin; Rai, Shesh Nath; Ghim, Shin je; Miller, Donald [James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky (United States)

    2016-01-01

    Purpose: Because a combination of retinoic acid, interferon-alpha, and radiation therapy demonstrated synergistic action and effectiveness to treat advanced cervical cancers in earlier studies, we designed this randomized phase 2 open-label trial to assess efficacy and safety of interferon alpha-2b (IFN) and 13-cis-retinoic acid (RA) administered concomitantly with radiation therapy (IFN-RA-radiation) to treat stage III cervical cancer. Methods and Materials: Stage III cervical cancer patients were randomized to study and control groups in a 1:1 ratio. All patients were treated with radiation therapy; study arm patients received IFN (3 × 10{sup 6} IU subcutaneously) 3 times a week for 4 weeks and daily RA (40 mg orally) for 30 days starting on day 1 of radiation, whereas control arm patients received weekly cisplatinum (40 mg/m{sup 2}) for 5 weeks during radiation. Patients were followed for 3 years. The primary endpoint was overall survival at 3 years. Results: Patients in the study (n=104) and control (n=105) groups were comparable for clinicopathological characteristics, radiation therapy–related variables and treatment response. Proportions of disease-free patients in the study and control groups were 38.5% and 44.8%, respectively, after median follow-up of 29.2 months. Hazard ratios were 0.67 (95% confidence interval [CI]: 0.44-1.01) and 0.69 (95% CI: 0.44-1.06) for overall and disease-fee survival, respectively, comparing the study group to control, and demonstrated an inferior outcome with RA-IFN-radiation, although differences were statistically nonsignificant. Kaplan-Meier curves of disease-free and overall survival probabilities also showed inferior survival in the study group compared to those in the control. Acute toxicities of chemoradiation were significantly higher with 2 acute toxicity-related deaths. Conclusions: Treatment with RA-IFN-radiation did not demonstrate survival advantage over chemoradiation despite being less toxic. The

  9. Cognitive enhancement treatments for bipolar disorder

    DEFF Research Database (Denmark)

    Miskowiak, Kamilla W; Carvalho, André F; Vieta, Eduard

    2016-01-01

    Cognitive dysfunction is an emerging treatment target in bipolar disorder (BD). Several trials have assessed the efficacy of novel pharmacological and psychological treatments on cognition in BD but the findings are contradictory and unclear. A systematic search following the PRISMA guidelines...... was conducted on PubMed and PsychInfo. Eligible articles reported randomized, controlled or open-label trials investigating pharmacological or psychological treatments targeting cognitive dysfunction in BD. The quality of the identified randomized controlled trials (RCTs) was evaluated with the Cochrane...... Collaboration's Risk of Bias tool. We identified 19 eligible studies of which 13 were RCTs and six were open-label or non-randomized studies. The findings regarding efficacy on cognition were overall disappointing or preliminary, possibly due to several methodological challenges. For the RCTs, the risk of bias...

  10. Experience in the quality control of commercial and self-labelled radiopharmaceuticals

    International Nuclear Information System (INIS)

    Strehlau, E.; Weiland, J.

    1980-01-01

    Different methods of quality control of radiopharmaceuticals checked in the laboratory practice are summarized. Starting from the general organization of quality control in the clinical radiochemical laboratory methods of analysis and working regulations are discussed. The quality tests of sup(99m)Tc-generator eluate, that is the testing for radioactive contaminants and for soluble aluminium as well as the testing of sup(99m)Tc-labelled kits and of different other frequently used radiopharmaceuticals are described in detail. Special conditions of examination and results of chromatography and medium-voltage electrophoresis are also given. Furthermore the routine determination of the output in the labelling of denaturated erythrocytes with sup(99m)Tc is discussed. The clinical practice in the case of preparation deficiencies and of possible incidents following the application of radiopharmaceuticals is outlined. (author)

  11. An Analysis of Patient Adherence to Treatment during a 1-Year, Open-Label Study of OROS[R] Methylphenidate in Children with ADHD

    Science.gov (United States)

    Faraone, Stephen V.; Biederman, Joseph; Zimmerman, Brenda

    2007-01-01

    Objective: Treatment adherence is an important aspect of ADHD symptom management, but there are many factors that may influence adherence. Method: This analysis assessed adherence to OROS methylphenidate during a 1-year, open-label study in children. Adherence was defined as the number of days medication was taken divided by the number of days in…

  12. Randomized controlled trial in rural Ethiopia to assess a portable water treatment device.

    Science.gov (United States)

    Boisson, Sophie; Schmidt, Wolf-Peter; Berhanu, Tsegahiwot; Gezahegn, Henock; Clasen, Thomas

    2009-08-01

    We conducted a randomized controlled trial to assess the Lifestraw Personal pipe-style water treatment device among a rural population in Ethiopia. A total of 313 households (including 1516 persons) were randomly assigned either to an intervention group in which each householder received a Lifestraw Personal or a control. Households were visited fortnightly over a five-month intervention period and asked to report any episode of diarrhea during the previous week. A random sample of 160 devices was tested each month to assess the presence of thermotolerant coliforms (TTC) and residual iodine in treated water and to measure flow rate under simulated use. Members of the intervention group had 25% fewer weeks with diarrhea than those of the control group (longitudinal prevalence ratio = 0.75; 95% CI 0.60; 0.95). All 718 filtered water samples were free of TTC, were free of detectable iodine disinfectant, and showed a constant flow rate over time. After the five-month intervention period, 34% of participants reported use of device in the preceding week and 13% reported consistent use. While the device was associated with a 25% reduction in longitudinal prevalence of diarrhea, low levels of use suggest that much of this effect is likely to be attributable to reporting bias that is common in open trials with nonobjective outcomes.

  13. Multimodal analgesia versus traditional opiate based analgesia after cardiac surgery, a randomized controlled trial

    DEFF Research Database (Denmark)

    Rafiq, Sulman; Steinbrüchel, Daniel Andreas; Wanscher, Michael Jaeger

    2014-01-01

    BACKGROUND: To evaluate if an opiate sparing multimodal regimen of dexamethasone, gabapentin, ibuprofen and paracetamol had better analgesic effect, less side effects and was safe compared to a traditional morphine and paracetamol regimen after cardiac surgery. METHODS: Open-label, prospective...

  14. Long-term treatment of patients with idiopathic pulmonary fibrosis with nintedanib: results from the TOMORROW trial and its open-label extension.

    Science.gov (United States)

    Richeldi, Luca; Kreuter, Michael; Selman, Moisés; Crestani, Bruno; Kirsten, Anne-Marie; Wuyts, Wim A; Xu, Zuojun; Bernois, Katell; Stowasser, Susanne; Quaresma, Manuel; Costabel, Ulrich

    2017-10-09

    The TOMORROW trial of nintedanib comprised a randomised, placebo-controlled, 52-week period followed by a further blinded treatment period and an open-label extension. We assessed outcomes across these periods in patients randomised to nintedanib 150 mg twice daily or placebo at the start of TOMORROW. The annual rate of decline in FVC was -125.4 mL/year (95% CI -168.1 to -82.7) in the nintedanib group and -189.7 mL/year (95% CI -229.8 to -149.6) in the comparator group. The adverse event profile of nintedanib remained consistent throughout the studies. These results support a benefit of nintedanib on slowing progression of idiopathic pulmonary fibrosis beyond 52 weeks. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  15. 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.

  16. Autologous Bone Marrow Mononuclear Cell Therapy for Autism: An Open Label Proof of Concept Study

    Directory of Open Access Journals (Sweden)

    Alok Sharma

    2013-01-01

    Full Text Available Cellular therapy is an emerging therapeutic modality with a great potential for the treatment of autism. Recent findings show that the major underlying pathogenetic mechanisms of autism are hypoperfusion and immune alterations in the brain. So conceptually, cellular therapy which facilitates counteractive processes of improving perfusion by angiogenesis and balancing inflammation by immune regulation would exhibit beneficial clinical effects in patients with autism. This is an open label proof of concept study of autologous bone marrow mononuclear cells (BMMNCs intrathecal transplantation in 32 patients with autism followed by multidisciplinary therapies. All patients were followed up for 26 months (mean 12.7. Outcome measures used were ISAA, CGI, and FIM/Wee-FIM scales. Positron Emission Tomography-Computed Tomography (PET-CT scan recorded objective changes. Out of 32 patients, a total of 29 (91% patients improved on total ISAA scores and 20 patients (62% showed decreased severity on CGI-I. The difference between pre- and postscores was statistically significant (P<0.001 on Wilcoxon matched-pairs signed rank test. On CGI-II 96% of patients showed global improvement. The efficacy was measured on CGI-III efficacy index. Few adverse events including seizures in three patients were controlled with medications. The encouraging results of this leading clinical study provide future directions for application of cellular therapy in autism.

  17. Human action analysis with randomized trees

    CERN Document Server

    Yu, Gang; Liu, Zicheng

    2014-01-01

    This book will provide a comprehensive overview on human action analysis with randomized trees. It will cover both the supervised random trees and the unsupervised random trees. When there are sufficient amount of labeled data available, supervised random trees provides a fast method for space-time interest point matching. When labeled data is minimal as in the case of example-based action search, unsupervised random trees is used to leverage the unlabelled data. We describe how the randomized trees can be used for action classification, action detection, action search, and action prediction.

  18. CLS A Fully Open-Source Control System

    CERN Document Server

    Matias, Elder; Johnson, Terry; Tanner, Robby; Wilson, Tony; Wright, Glen; Zhang, Hao

    2005-01-01

    The Canadian Light Source is one of the first major accelerator facility to adopt a fully open source control system. The control system is based on Experimental Physics and Industrial Control System (EPICS) in use at may other facilities. From the outset CLS utilised RTEMS and Linux as the underlying operating systems for real-time control computers, operator interface computers and servers. When communicating with PLC and other intelligent devices CLS has also adopted a policy of using open communications protocols where possible. Combined these strategies have lead to a system that can easily evolve over the life of the facility without being tied to specific hardware or software suppliers. The operational experience over the past few years has indicates the selected architecture is sufficiently robust and reliable.

  19. Prophylactic platelet transfusion plus supportive care versus supportive care alone in adults with dengue and thrombocytopenia: a multicentre, open-label, randomised, superiority trial.

    Science.gov (United States)

    Lye, David C; Archuleta, Sophia; Syed-Omar, Sharifah F; Low, Jenny G; Oh, Helen M; Wei, Yuan; Fisher, Dale; Ponnampalavanar, Sasheela S L; Wijaya, Limin; Lee, Linda K; Ooi, Eng-Eong; Kamarulzaman, Adeeba; Lum, Lucy C; Tambyah, Paul A; Leo, Yee-Sin

    2017-04-22

    Dengue is the commonest vector-borne infection worldwide. It is often associated with thrombocytopenia, and prophylactic platelet transfusion is widely used despite the dearth of robust evidence. We aimed to assess the efficacy and safety of prophylactic platelet transfusion in the prevention of bleeding in adults with dengue and thrombocytopenia. We did an open-label, randomised, superiority trial in five hospitals in Singapore and Malaysia. We recruited patients aged at least 21 years who had laboratory-confirmed dengue (confirmed or probable) and thrombocytopenia (≤20 000 platelets per μL), without persistent mild bleeding or any severe bleeding. Patients were assigned (1:1), with randomly permuted block sizes of four or six and stratified by centre, to receive prophylactic platelet transfusion in addition to supportive care (transfusion group) or supportive care alone (control group). In the transfusion group, 4 units of pooled platelets were given each day when platelet count was 20 000 per μL or lower; supportive care consisted of bed rest, fluid therapy, and fever and pain medications. The primary endpoint was clinical bleeding (excluding petechiae) by study day 7 or hospital discharge (whichever was earlier), analysed by intention to treat. Safety outcomes were analysed according to the actual treatment received. This study was registered with ClinicalTrials.gov, number NCT01030211, and is completed. Between April 29, 2010, and Dec 9, 2014, we randomly assigned 372 patients to the transfusion group (n=188) or the control group (n=184). The intention-to-treat analysis included 187 patients in the transfusion group (one patient was withdrawn immediately) and 182 in the control group (one was withdrawn immediately and one did not have confirmed or probable dengue). Clinical bleeding by day 7 or hospital discharge occurred in 40 (21%) patients in the transfusion group and 48 (26%) patients in the control group (risk difference -4·98% [95% CI -15·08 to

  20. Effect of Daikenchuto (TJ-100) on gastrointestinal symptoms following laparoscopic colectomy in patients with colon cancer: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Hoshino, Nobuaki; Kawada, Kenji; Hida, Koya; Wada, Toshiaki; Takahashi, Ryo; Yoshitomi, Mami; Sakai, Yoshiharu

    2017-11-21

    Postoperative paralytic ileus can be a difficult complication for both surgeons and patients. Causes and treatments have been discussed for more than two centuries, but have not yet been fully resolved. Daikenchuto (TJ-100, DKT) is a traditional Japanese herbal medicine. Recently, some beneficial mechanisms of DKT to relieve paralytic ileus have been reported. DKT can suppress inflammation, increase intestinal blood flow, and accelerate bowel movements. Therefore, we have designed a randomized controlled trial to investigate the effects of DKT on postoperative gastrointestinal symptoms following laparoscopic colectomy in patients with left-sided colon cancer at a single institution. As primary endpoints, the following outcomes will be evaluated: (i) grade of abdominal pain determined using the numeric rating scale (NRS), (ii) grade of abdominal distention determined using the NRS, and (iii) quality of life determined using the Gastrointestinal Quality Life Index (GIQLI). As secondary endpoints, the following will be evaluated: (i) postoperative nutritional status (Onodera's Prognostic Nutritional Index (PNI) and the Controlling Nutritional Status score (CONUT score)), (ii) duration to initial flatus, (iii) duration to initial defecation, (iv) bowel gas volume, (v) character of stool (Bristol Stool Form Scale), (vi) defecation frequency per day, (vii) postoperative complications (Clavien-Dindo classification), (viii) length of postoperative hospital stay, and (ix) metabolites in the stool and blood. This trial is an open-label study, and needs to include 40 patients (20 patients per group) and is expected to span 2 years. To our knowledge, this is the first randomized controlled trial to investigate the effects of DKT on postoperative subjective outcomes (i.e., postoperative quality of life) following laparoscopic colectomy as primary endpoints. Exploratory metabolomics analysis of metabolites in stool and blood will be conducted in this trial, which previously has

  1. Effect of Micronutrients on Behavior and Mood in Adults with ADHD: Evidence from an 8-Week Open Label Trial with Natural Extension

    Science.gov (United States)

    Rucklidge, Julia; Taylor, Mairin; Whitehead, Kathryn

    2011-01-01

    Objective: To investigate the effect of a 36-ingredient micronutrient formula consisting mainly of minerals and vitamins in the treatment of adults with both ADHD and severe mood dysregulation (SMD). Method: 14 medication-free adults (9 men, 5 women; 18-55 years) with ADHD and SMD completed an 8-week open-label trial. Results: A minority reported…

  2. Effects of Different Types of Front-of-Pack Labelling Information on the Healthiness of Food Purchases—A Randomised Controlled Trial

    Directory of Open Access Journals (Sweden)

    Bruce Neal

    2017-11-01

    Full Text Available Background: Front-of-pack nutrition labelling may support healthier packaged food purchases. Australia has adopted a novel Health Star Rating (HSR system, but the legitimacy of this choice is unknown. Objective: To define the effects of different formats of front-of-pack labelling on the healthiness of food purchases and consumer perceptions. Design: Individuals were assigned at random to access one of four different formats of nutrition labelling—HSR, multiple traffic light labels (MTL, daily intake guides (DIG, recommendations/warnings (WARN—or control (the nutrition information panel, NIP. Participants accessed nutrition information by using a smartphone application to scan the bar-codes of packaged foods, while shopping. The primary outcome was healthiness defined by the mean transformed nutrient profile score of packaged foods that were purchased over four weeks. Results: The 1578 participants, mean age 38 years, 84% female recorded purchases of 148,727 evaluable food items. The mean healthiness of the purchases in the HSR group was non-inferior to MTL, DIG, or WARN (all p < 0.001 at 2% non-inferiority margin. When compared to the NIP control, there was no difference in the mean healthiness of purchases for HSR, MTL, or DIG (all p > 0.07, but WARN resulted in healthier packaged food purchases (mean difference 0.87; 95% confidence interval 0.03 to 1.72; p = 0.04. HSR was perceived by participants as more useful than DIG, and easier to understand than MTL or DIG (all p < 0.05. Participants also reported the HSR to be easier to understand, and the HSR and MTL to be more useful, than NIP (all p < 0.03. Conclusions: These real-world data align with experimental findings and provide support for the policy choice of HSR. Recommendation/warning labels warrant further exploration, as they may be a stronger driver of healthy food purchases.

  3. 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

  4. 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

  5. The Effect of Medicinal Cannabis on Pain and Quality-of-Life Outcomes in Chronic Pain: A Prospective Open-label Study.

    Science.gov (United States)

    Haroutounian, Simon; Ratz, Yael; Ginosar, Yehuda; Furmanov, Karina; Saifi, Fayez; Meidan, Ronit; Davidson, Elyad

    2016-12-01

    The objective of this prospective, open-label study was to determine the long-term effect of medicinal cannabis treatment on pain and functional outcomes in participants with treatment-resistant chronic pain. The primary outcome was the change in the pain symptom score on the S-TOPS (Treatment Outcomes in Pain Survey-Short Form) questionnaire at the 6-month follow-up in an intent-to-treat population. Secondary outcomes included the change in S-TOPS physical, social, and emotional disability scales, the pain severity, and pain interference on the Brief Pain Inventory, sleep problems, and the change in opioid consumption. A total of 274 participants were approved for treatment; complete baseline data were available for 206 (intent-to-treat), and complete follow-up data for 176 participants. At follow-up, the pain symptom score improved from median 83.3 (95% confidence interval [CI], 79.2-87.5) to 75.0 (95% CI, 70.8-79.2) (Pmedicinal cannabis in this open-label, prospective cohort resulted in improved pain and functional outcomes, and a significant reduction in opioid use. Results suggest long-term benefit of cannabis treatment in this group of patients, but the study's noncontrolled nature should be considered when extrapolating the results.

  6. Behavioral Outcome Effects of Serious Gaming as an Adjunct to Treatment for Children With Attention-Deficit/Hyperactivity Disorder: A Randomized Controlled Trial.

    Science.gov (United States)

    Bul, Kim C M; Kato, Pamela M; Van der Oord, Saskia; Danckaerts, Marina; Vreeke, Leonie J; Willems, Annik; van Oers, Helga J J; Van Den Heuvel, Ria; Birnie, Derk; Van Amelsvoort, Thérèse A M J; Franken, Ingmar H A; Maras, Athanasios

    2016-02-16

    The need for accessible and motivating treatment approaches within mental health has led to the development of an Internet-based serious game intervention (called "Plan-It Commander") as an adjunct to treatment as usual for children with attention-deficit/hyperactivity disorder (ADHD). The aim was to determine the effects of Plan-It Commander on daily life skills of children with ADHD in a multisite randomized controlled crossover open-label trial. Participants (N=170) in this 20-week trial had a diagnosis of ADHD and ranged in age from 8 to 12 years (male: 80.6%, 137/170; female: 19.4%, 33/170). They were randomized to a serious game intervention group (group 1; n=88) or a treatment-as-usual crossover group (group 2; n=82). Participants randomized to group 1 received a serious game intervention in addition to treatment as usual for the first 10 weeks and then received treatment as usual for the next 10 weeks. Participants randomized to group 2 received treatment as usual for the first 10 weeks and crossed over to the serious game intervention in addition to treatment as usual for the subsequent 10 weeks. Primary (parent report) and secondary (parent, teacher, and child self-report) outcome measures were administered at baseline, 10 weeks, and 10-week follow-up. After 10 weeks, participants in group 1 compared to group 2 achieved significantly greater improvements on the primary outcome of time management skills (parent-reported; P=.004) and on secondary outcomes of the social skill of responsibility (parent-reported; P=.04), and working memory (parent-reported; P=.02). Parents and teachers reported that total social skills improved over time within groups, whereas effects on total social skills and teacher-reported planning/organizing skills were nonsignificant between groups. Within group 1, positive effects were maintained or further improved in the last 10 weeks of the study. Participants in group 2, who played the serious game during the second period of the

  7. Behavioral Outcome Effects of Serious Gaming as an Adjunct to Treatment for Children With Attention-Deficit/Hyperactivity Disorder: A Randomized Controlled Trial

    Science.gov (United States)

    2016-01-01

    Background The need for accessible and motivating treatment approaches within mental health has led to the development of an Internet-based serious game intervention (called “Plan-It Commander”) as an adjunct to treatment as usual for children with attention-deficit/hyperactivity disorder (ADHD). Objective The aim was to determine the effects of Plan-It Commander on daily life skills of children with ADHD in a multisite randomized controlled crossover open-label trial. Methods Participants (N=170) in this 20-week trial had a diagnosis of ADHD and ranged in age from 8 to 12 years (male: 80.6%, 137/170; female: 19.4%, 33/170). They were randomized to a serious game intervention group (group 1; n=88) or a treatment-as-usual crossover group (group 2; n=82). Participants randomized to group 1 received a serious game intervention in addition to treatment as usual for the first 10 weeks and then received treatment as usual for the next 10 weeks. Participants randomized to group 2 received treatment as usual for the first 10 weeks and crossed over to the serious game intervention in addition to treatment as usual for the subsequent 10 weeks. Primary (parent report) and secondary (parent, teacher, and child self-report) outcome measures were administered at baseline, 10 weeks, and 10-week follow-up. Results After 10 weeks, participants in group 1 compared to group 2 achieved significantly greater improvements on the primary outcome of time management skills (parent-reported; P=.004) and on secondary outcomes of the social skill of responsibility (parent-reported; P=.04), and working memory (parent-reported; P=.02). Parents and teachers reported that total social skills improved over time within groups, whereas effects on total social skills and teacher-reported planning/organizing skills were nonsignificant between groups. Within group 1, positive effects were maintained or further improved in the last 10 weeks of the study. Participants in group 2, who played the

  8. 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.

  9. Evaluation of Subcutaneous Proleukin (interleukin-2) in a Randomized International Trial (ESPRIT): geographical and gender differences in the baseline characteristics of participants

    NARCIS (Netherlands)

    Pett, S. L.; Wand, H.; Law, M. G.; Arduino, R.; Lopez, J. C.; Knysz, B.; Pereira, L. C.; Pollack, S.; Reiss, P.; Tambussi, G.

    2006-01-01

    BACKGROUND: ESPRIT, is a phase III, open-label, randomized, international clinical trial evaluating the effects of subcutaneous recombinant interleukin-2 (rIL-2) plus antiretroviral therapy (ART) versus ART alone on HIV-disease progression and death in HIV-1-infected individuals with CD4+ T-cells >

  10. 21 CFR 1302.04 - Location and size of symbol on label and labeling.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Location and size of symbol on label and labeling... AND PACKAGING REQUIREMENTS FOR CONTROLLED SUBSTANCES § 1302.04 Location and size of symbol on label and labeling. The symbol shall be prominently located on the label or the labeling of the commercial...

  11. Access control mechanism of wireless gateway based on open flow

    Science.gov (United States)

    Peng, Rong; Ding, Lei

    2017-08-01

    In order to realize the access control of wireless gateway and improve the access control of wireless gateway devices, an access control mechanism of SDN architecture which is based on Open vSwitch is proposed. The mechanism utilizes the features of the controller--centralized control and programmable. Controller send access control flow table based on the business logic. Open vSwitch helps achieve a specific access control strategy based on the flow table.

  12. Miglustat in late-onset Tay-Sachs disease: a 12-month, randomized, controlled clinical study with 24 months of extended treatment.

    Science.gov (United States)

    Shapiro, Barbara E; Pastores, Gregory M; Gianutsos, John; Luzy, Cécile; Kolodny, Edwin H

    2009-06-01

    To evaluate the safety and efficacy of miglustat in patients with GM2 gangliosidosis. A randomized, multicenter, open-label, 12-month study involving patients aged 18 years or older, randomized 2:1 to miglustat (200 mg TID) or "no miglustat treatment." This study was followed by 24 months of extended treatment during which all patients received miglustat. Primary efficacy endpoints were change in eight measures of isometric muscle strength in the limbs and isometric grip strength, evaluated at baseline, and months 12 and 36. Secondary efficacy endpoints included gait, balance, disability, and other neurological assessments. Safety evaluations included adverse event reporting. Thirty patients (67% male, age range 18-56 years) with late-onset Tay-Sachs disease were enrolled; 20 were randomized to miglustat and 10 to "no miglustat treatment." Muscle and grip strength generally decreased over the study period. No differences were observed between the two groups in any efficacy measure, either during the 12-month randomized phase or the full 36 months. The most common treatment-related adverse events were decrease in weight and diarrhea. Miglustat treatment was not shown to lead to measurable benefits in this cohort of patients with late-onset Tay-Sachs disease. The observed safety profile was consistent with that of the approved dose (100 mg TID) in type 1 Gaucher disease.

  13. An open-label pilot study of pulsed electromagnetic field therapy in the treatment of failed back surgery syndrome pain

    Directory of Open Access Journals (Sweden)

    Harper WL

    2014-12-01

    Full Text Available Wayne L Harper,1 William K Schmidt,2 Nicole J Kubat,3 Richard A Isenberg41Tarheel Clinical Research, LLC, Raleigh, NC, USA; 2NorthStar Consulting, LLC, Davis, CA, USA; 3Nicole Kubat Consulting, Pasadena, CA, USA; 4Regenesis Biomedical, Inc., Scottsdale, AZ, USAAbstract: Persistent pain following back surgery remains a major treatment challenge. The primary objective of this open-label exploratory study was to investigate the analgesic effectiveness of pulsed electromagnetic field therapy administered twice daily over a 45-day period in 34 subjects (68% female with persistent or recurrent pain following back surgery. A secondary goal was to guide the design of future randomized controlled trials that could target responsive subpopulations. All predefined primary and secondary outcomes, including change in pain intensity (PI, physical function (Oswestry Disability Index, analgesic consumption, and overall well-being (Patient Global Impression of Change, are reported. A responder analysis (≥30% reduction in PI versus baseline was added as a post hoc evaluation. Safety outcomes, as well as results of a cost-avoidance survey, are also summarized. Of the 30 per-protocol subjects who completed the study, 33% reported a clinically meaningful (≥30% reduction in PI. A higher response rate (60% was reported for subjects who had undergone discectomy prior to the trial compared to subjects who had undergone other types of surgical interventions (decompression or fusion without discectomy. Improvements in PI were paralleled by improvements in secondary outcomes. Relative to baseline, responders reported an average 44% and 55% reduction in back PI and leg PI (respectively, and an average 13% improvement in Oswestry Disability Index scores. In the per-protocol population, 50% of responders and 12% of nonresponders reported less analgesia consumption at the end of treatment versus baseline. Sixty-seven percent of per-protocol responders and 0% of

  14. 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.

  15. Detection of myocardial ischemia before infarction, based on accumulation of labeled pyruvate

    International Nuclear Information System (INIS)

    Goldstein, R.A.; Klein, M.S.; Sobel, B.E.

    1980-01-01

    To determine whether ischemic, but not irreversibly injured myocardium, can be differentiated from normal tissue based on accumulation of labeled pyruvate, isolated hearts were perfused with buffer containing [ 14 C]pyruvate under conditions of normal or low flow. Fifteen minutes after the hearts were exposed to labeled material, myocardial radioactivity was fourfold greater in ischemic compared to control hearts, due to accumulation of label in sequestered lactate produced from the pyruvate. Open-chest rabbits subjected to coronary occlusion exhibited a 1.73:1 ratio of radioactivity in ischemic compared with normal myocardium 15 min after systemic injection of [ 14 C]pyruvate. The results obtained suggest that zones of myocardial ischemia should be detectable in vivo by positron tomography after systemic administration of [ 11 C]pyruvate as well

  16. Attrition during a randomized controlled trial of reduced nicotine content cigarettes as a proxy for understanding acceptability of nicotine product standards.

    Science.gov (United States)

    Mercincavage, Melissa; Wileyto, E Paul; Saddleson, Megan L; Lochbuehler, Kirsten; Donny, Eric C; Strasser, Andrew A

    2017-06-01

    To determine (1) if nicotine content affects study attrition-a potential behavioral measure of acceptability-in a trial that required compliance with three levels of reduced nicotine content (RNC) cigarettes, and (2) if attrition is associated with subjective and behavioral responses to RNC cigarettes. Secondary analysis of a 35-day, parallel-design, open-label, randomized controlled trial. After a 5-day baseline period, participants were randomized to smoke for three 10-day periods: their preferred brand (control group) or RNC cigarettes with three nicotine levels in a within-subject stepdown (one group: high-moderate-low) or non-stepdown (five groups: high-low-moderate, low-moderate-high, low-high-moderate, moderate-low-high, moderate-high-low) fashion. A single site in Philadelphia, PA, USA. A total of 246 non-treatment-seeking daily smokers [mean age = 39.52, cigarettes per day (CPD) = 20.95, 68.3% white] were recruited from October 2007 to June 2013. The primary outcome was attrition. Key predictors were nicotine content transition and study period. Exploratory predictors were taste and strength subjective ratings, total puff volume and carbon monoxide (CO) boost. Covariates included: age, gender, race, education and nicotine dependence. Overall attrition was 31.3% (n = 77): 24.1% of the control and 25.0% of the stepdown RNC cigarette groups dropped out versus 44.6% of non-stepdown groups (P = 0.006). Compared with controls, attrition odds were 4.5 and 4.7 times greater among smokers transitioning from preferred and the highest RNC cigarettes to the lowest RNC cigarettes, respectively (P = 0.001 and 0.003). Providing more favorable initial taste ratings of study cigarettes decreased attrition odds by 2% (P = 0.012). The majority of participants completed a 35-day trial of varying levels of reduced nicotine content cigarettes. Participant dropout was greater for cigarettes with lower nicotine content and less in smokers reporting more favorable

  17. A randomized trial comparing initial HAART regimens of nelfinavir/nevirapine and ritonavir/saquinavir in combination with two nucleoside reverse transcriptase inhibitors

    DEFF Research Database (Denmark)

    Kirk, Ole; Lundgren, Jens D; Pedersen, Court

    2003-01-01

    BACKGROUND: A triple-class HAART regimen may be associated with a better virological effect than conventional regimens, but may also lead to toxicity and more profound resistance. METHODS: Randomized, controlled, open-label trial of 233 protease inhibitor- and non-nucleoside reverse transcriptase...... inhibitor-naive HIV-infected patients allocated to a regimen of nelfinavir and nevirapine (1250/200 mg twice daily; n = 118) or ritonavir and saquinavir (400/400 mg twice daily; n = 115), both in combination with two nucleoside reverse transcriptase inhibitors. The primary end-point was HIV RNA ... the long-term consequences of triple class HAART regimens, including the development of broad drug resistance....

  18. A Randomized Double-Blind Placebo-Controlled Study of Omalizumab Combined with Oral Immunotherapy for the Treatment of Cow’s Milk Allergy

    Science.gov (United States)

    Wood, Robert A.; Kim, Jennifer S.; Lindblad, Robert; Nadeau, Kari; Henning, Alice K.; Dawson, Peter; Plaut, Marshall; Sampson, Hugh A.

    2017-01-01

    Background Although studies of oral immunotherapy (OIT) for food allergy have shown promise, treatment is frequently complicated by adverse reactions and, even when successful, has limited long-term efficacy as benefits usually diminish when treatment is discontinued. Objective We sought to examine whether the addition of omalizumab to milk OIT (MOIT) reduces treatment-related reactions and/or improves outcomes. Methods This was a double-blind placebo-controlled trial with subjects randomized to omalizumab or placebo. Open-label MOIT was initiated after 4 months of omalizumab/placebo with escalation to maintenance over 22–40 weeks, followed by daily maintenance dosing through month-28. At month-28, omalizumab was discontinued and subjects passing an oral food challenge (OFC) continued OIT for 8 weeks, after which OIT was discontinued with re-challenge at month-32 to assess sustained unresponsiveness (SU). Results Fifty-seven subjects (7–32 years) were randomized, with no significant baseline differences in age, milk-specific IgE, skin tests, or OFCs. At month-28, 24 (88.9%) omalizumab-treated subjects and 20 (71.4%) placebo-treated subjects passed the 10 gram “desensitization” OFC (p=0.18). At month-32, SU was demonstrated in 48.1% in the omalizumab group and 35.7% in the placebo group (p=0.42). Adverse reactions were markedly reduced during OIT escalation in omalizumab subjects for percent doses/subject provoking symptoms (2.1% versus 16.1%; p=0.0005), dose-related reactions requiring treatment (0.0% versus 3.8%, p=0.0008), and doses required to achieve maintenance (198 versus 225; p=0.008). Conclusions In this first randomized double-blinded placebo-controlled trial of omalizumab in combination with food OIT, we found significant improvements in measurements of safety, but not in outcomes of efficacy (desensitization and SU). Trial Registration OIT and XolairR (Omalizumab) in Cow’s Milk Allergy, NCT01157117, http://clinicaltrials.gov/show/NCT01157117

  19. An improved label propagation algorithm based on node importance and random walk for community detection

    Science.gov (United States)

    Ma, Tianren; Xia, Zhengyou

    2017-05-01

    Currently, with the rapid development of information technology, the electronic media for social communication is becoming more and more popular. Discovery of communities is a very effective way to understand the properties of complex networks. However, traditional community detection algorithms consider the structural characteristics of a social organization only, with more information about nodes and edges wasted. In the meanwhile, these algorithms do not consider each node on its merits. Label propagation algorithm (LPA) is a near linear time algorithm which aims to find the community in the network. It attracts many scholars owing to its high efficiency. In recent years, there are more improved algorithms that were put forward based on LPA. In this paper, an improved LPA based on random walk and node importance (NILPA) is proposed. Firstly, a list of node importance is obtained through calculation. The nodes in the network are sorted in descending order of importance. On the basis of random walk, a matrix is constructed to measure the similarity of nodes and it avoids the random choice in the LPA. Secondly, a new metric IAS (importance and similarity) is calculated by node importance and similarity matrix, which we can use to avoid the random selection in the original LPA and improve the algorithm stability. Finally, a test in real-world and synthetic networks is given. The result shows that this algorithm has better performance than existing methods in finding community structure.

  20. A randomized control trial to evaluate the effect of adjuvant selective laser trabeculoplasty versus medication alone in primary open-angle glaucoma: preliminary results

    Directory of Open Access Journals (Sweden)

    Lee JWY

    2014-09-01

    Full Text Available Jacky WY Lee,1,2 Catherine WS Chan,2 Mandy OM Wong,3 Jonathan CH Chan,3 Qing Li,2 Jimmy SM Lai2 1The Department of Ophthalmology, Caritas Medical Centre, 2The Department of Ophthalmology, The University of Hong Kong, 3The Department of Ophthalmology, Queen Mary Hospital, Hong Kong Background: The objective of this study was to investigate the effects of adjuvant selective laser trabeculoplasty (SLT versus medication alone on intraocular pressure (IOP control, medication use, and quality of life in patients with primary open-angle glaucoma.Methods: This prospective, randomized control study recruited 41 consecutive primary open-angle glaucoma subjects with medically-controlled IOP ≤21 mmHg. The SLT group (n=22 received a single 360-degree SLT treatment. The medication-only group (n=19 continued with their usual treatment regimen. In both groups, medication was titrated to maintain a target IOP defined as a 25% reduction from baseline IOP without medication, or <18 mmHg, whichever was lower. Outcomes, which were measured at baseline and at 6 months, included the Glaucoma Quality of Life-15 (GQL-15 and Comparison of Ophthalmic Medications for Tolerability (COMTOL survey scores, IOP, and the number of antiglaucoma medicines. Results: The baseline IOP was 15.8±2.7 mmHg and 14.5±2.5 mmHg in the SLT and medication-only groups, respectively (P=0.04. Both groups had a comparable number of baseline medication (P=0.2, GQL-15 (P=0.3 and COMTOL scores (P=0.7. At 6 months, the SLT group had a lower IOP (P=0.03 and required fewer medications compared with both baseline (P<0.0001 and with the medication-only group (P=0.02. There was no statistically significant difference in the 6-month GQL-15 or COMTOL score as compared to baseline (P≥0.4 or between the two treatment groups (P≥0.2.Conclusion: A single session of adjuvant SLT provided further reductions in IOP and medication without substantial changes in quality of life or medication tolerability at 6

  1. Open loop thanks to direct torque control (DTC). Motor control without feedback loop; Open loop dank direkter Drehmomentregelung (DTC). Hochwertige Motorregelung ohne Rueckfuehrung

    Energy Technology Data Exchange (ETDEWEB)

    Link, Michael [ABB Automation Products GmbH, Ladenburg (Germany)

    2009-07-01

    Servo drives are used in various applications. The range of applications is huge and thus also requirements to the drive system. Mainly, a fast torque and speed control is required. This is the domaine of direct torque control (DTC). In many applications DTC can meet this challenge to control the motor with full torque at zero speed. The servo converter based on DTC technology provides a control concept for synchronous and asynchronous motors for both closed loop and open loop control. DTC controlled drives support the whole range from open loop up to high performance motion control applications. (orig.)

  2. 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.

  3. 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.

  4. 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.

  5. Impact of baseline BMI on glycemic control and weight change with metformin monotherapy in Chinese type 2 diabetes patients: phase IV open-label trial.

    Directory of Open Access Journals (Sweden)

    Linong Ji

    Full Text Available Differences exist between treatment recommendations regarding the choice of metformin as first-line therapy for type 2 diabetes patients according to body mass index (BMI. This study compared the efficacy of metformin monotherapy among normal-weight, overweight, and obese patients with newly diagnosed type 2 diabetes.In this prospective, multicenter, open-label study in China, patients aged 23-77 years were enrolled 1∶1:1 according to baseline BMI: normal-weight (BMI 18.5-23.9 kg/m(2; n = 125; overweight (BMI 24.0-27.9 kg/m(2; n = 122 or obese (BMI ≥28 kg/m(2; n = 124. Extended-release metformin was administered for 16 weeks (500 mg/day, up-titrated weekly to a maximum 2,000 mg/day. The primary efficacy endpoint was the effect of baseline BMI on glycemic control with metformin monotherapy, measured as the change from baseline in glycosylated hemoglobin (HbA1c at week 16 compared among BMI groups using ANCOVA. Other endpoints included comparisons of metformin's effects on fasting plasma glucose (FPG, lipid levels and body weight.Mean HbA1c decreases at week 16, adjusted for baseline values, were -1.84%, -1.78% and -1.78% in normal-weight, overweight and obese patients, (P = 0.664; body weight decreased by 2.4%, 3.9% and 3.5%, respectively. FPG levels decreased similarly over time in all BMI groups (P = 0.461 and changes from baseline in high-density lipoprotein cholesterol (HDL-C and low-density lipoprotein cholesterol (LDL-C did not differ significantly among BMI groups at week 16 (P = 0.143 and 0.451, respectively.Baseline BMI had no impact on glycemic control, weight change or other efficacy measures with metformin monotherapy. These data suggest that normal-weight type 2 diabetes patients would derive the same benefits from first-line treatment with metformin as overweight and obese patients, and are not at increased risk of excess weight loss.ClinicalTrials.gov NCT00778622.

  6. DNA probe labeling with digoxigenin-dUTP and its application in gene diagnosis

    International Nuclear Information System (INIS)

    Liu Guoyang

    1992-01-01

    DNA probe labeling by the randomly primed incorporation of digoxigenin-dUTP is reported. The sensitivity of color reaction and hybridization were 32 fg and 200 fg, respectively, and both were specific for the target. Single-copy and multi-copy gene fragments among 2 μg human genomic DNA were detected by β IVS II, Fr 3-42 and 3'HVR labeled with digoxigenin-dUTP. The results were consistent with a radioactive control assay. This method has been successfully used in the gene diagnosis of adult polycystic kidney disease

  7. Controlling open quantum systems: tools, achievements, and limitations

    International Nuclear Information System (INIS)

    Koch, Christiane P

    2016-01-01

    The advent of quantum devices, which exploit the two essential elements of quantum physics, coherence and entanglement, has sparked renewed interest in the control of open quantum systems. Successful implementations face the challenge of preserving relevant nonclassical features at the level of device operation. A major obstacle is decoherence, which is caused by interaction with the environment. Optimal control theory is a tool that can be used to identify control strategies in the presence of decoherence. Here we review recent advances in optimal control methodology that allow typical tasks in device operation for open quantum systems to be tackled and discuss examples of relaxation-optimized dynamics. Optimal control theory is also a useful tool to exploit the environment for control. We discuss examples and point out possible future extensions. (topical review)

  8. Effects of adaptive servo-ventilation therapy on cardiac function and remodeling in patients with chronic heart failure (SAVIOR-C): study protocol for a randomized controlled trial.

    Science.gov (United States)

    Seino, Yoshihiko; Momomura, Shin-Ichi; Kihara, Yasuki; Adachi, Hitoshi; Yasumura, Yoshio; Yokoyama, Hiroyuki

    2015-01-16

    Adaptive servo-ventilation (ASV) therapy, which is a form of noninvasive positive pressure ventilation therapy and uses an innovative ventilator that has simple operability and provides good patient adherence, potentially has therapeutic benefits-suppression of the deterioration and progression of chronic heart failure (CHF) and a reduction in the number of repeated hospitalizations. Therefore, ASV therapy draws attention as a novel, noninvasive nonpharmacotherapy for patients with CHF owing to its hemodynamics-improving effect, and it is currently being accepted in real-world clinical settings in Japan. However, clinical evidence sufficient for treatment recommendation is lacking because a multicenter, randomized, controlled study of ASV therapy has never been conducted. The present study is a confirmatory, prospective, multicenter, collaborative, open-label, blinded-endpoint, parallel-group, randomized, controlled study. At 40 medical institutions in Japan, 200 Japanese outpatients with mild to severe CHF (age: ≥ 20 years; New York Heart Association classification: greater than or equal to class II) will be randomly assigned to either of the following two study groups: the ASV group, in which 100 outpatients undergo guideline-directed medical therapy and ASV therapy for 24 weeks; and the control group, in which 100 outpatients undergo only guideline-directed medical therapy for 24 weeks. The objective of the present study is to confirm whether the ASV group is superior to the control group concerning the improvement of left ventricular contractility and remodeling, both assessed by two-dimensional echocardiography. Furthermore, the present study will also secondarily examine the effects of ASV therapy on the prognosis and quality of life of patients with CHF. ASV therapy using the device has the potential to provide therapeutic benefits based on its simple operability and good patient adherence and possesses the potential to improve left ventricular

  9. The first multicenter, randomized, controlled trial of home telemonitoring for Japanese patients with heart failure: home telemonitoring study for patients with heart failure (HOMES-HF).

    Science.gov (United States)

    Kotooka, Norihiko; Kitakaze, Masafumi; Nagashima, Kengo; Asaka, Machiko; Kinugasa, Yoshiharu; Nochioka, Kotaro; Mizuno, Atsushi; Nagatomo, Daisuke; Mine, Daigo; Yamada, Yoko; Kuratomi, Akiko; Okada, Norihiro; Fujimatsu, Daisuke; Kuwahata, So; Toyoda, Shigeru; Hirotani, Shin-Ichi; Komori, Takahiro; Eguchi, Kazuo; Kario, Kazuomi; Inomata, Takayuki; Sugi, Kaoru; Yamamoto, Kazuhiro; Tsutsui, Hiroyuki; Masuyama, Tohru; Shimokawa, Hiroaki; Momomura, Shin-Ichi; Seino, Yoshihiko; Sato, Yasunori; Inoue, Teruo; Node, Koichi

    2018-02-15

    Home telemonitoring is becoming more important to home medical care for patients with heart failure. Since there are no data on home telemonitoring for Japanese patients with heart failure, we investigated its effect on cardiovascular outcomes. The HOMES-HF study was the first multicenter, open-label, randomized, controlled trial (RCT) to elucidate the effectiveness of home telemonitoring of physiological data, such as body weight, blood pressure, and pulse rate, for Japanese patients with heart failure (UMIN Clinical Trials Registry 000006839). The primary end-point was a composite of all-cause death or rehospitalization due to worsening heart failure. We analyzed 181 recently hospitalized patients with heart failure who were randomly assigned to a telemonitoring group (n = 90) or a usual care group (n = 91). The mean follow-up period was 15 (range 0-31) months. There was no statistically significant difference in the primary end-point between groups [hazard ratio (HR), 0.95; 95% confidence interval (CI), 0.548-1.648; p = 0.572]. Home telemonitoring for Japanese patients with heart failure was feasible; however, beneficial effects in addition to those of usual care were not demonstrated. Further investigation of more patients with severe heart failure, participation of home medical care providers, and use of a more integrated home telemonitoring system emphasizing communication as well as monitoring of symptoms and physiological data are required.

  10. Dihydroartemisinin-piperaquine versus chloroquine to treat vivax malaria in Afghanistan: an open randomized, non-inferiority, trial

    Directory of Open Access Journals (Sweden)

    Woodrow Charles J

    2010-04-01

    Full Text Available Abstract Background Afghanistan's national guidelines recommend chloroquine for the treatment of Plasmodium vivax infection, the parasite responsible for the majority of its malaria burden. Chloroquine resistance in P. vivax is emerging in Asia. Therapeutic responses across Afghanistan have not been evaluated in detail. Methods Between July 2007 and February 2009, an open-label, randomized controlled trial of chloroquine and dihydroartemisinin-piperaquine in patients aged three months and over with slide-confirmed P. vivax mono-infections was conducted. Consistent with current national guidelines, primaquine was not administered. Subjects were followed up daily during the acute phase of illness (days 0-3 and weekly until day 56. The primary endpoint was the overall cumulative parasitological failure rate at day 56 after the start of treatment, with the hypothesis being that dihydroartemisinin-piperaquine was non-inferior compared to chloroquine (Δ = 5% difference in proportion of failures. Results Of 2,182 individuals with positive blood films for P. vivax, 536 were enrolled in the trial. The day 28 cure rate was 100% in both treatment groups. Parasite clearance was more rapid with dihydroartemisinin-piperaquine than chloroquine. At day 56, there were more recurrent infections in the chloroquine arm (8.9%, 95% CI 6.0-13.1% than the dihydroartemisinin-piperaquine arm (2.8%, 95% CI 1.4-5.8%, a difference in cumulative recurrence rate of 6.1% (2-sided 90%CI +2.6 to +9.7%. The log-rank test comparing the survival curves confirmed the superiority of dihydroartemisinin-piperaquine over chloroquine (p = 0.003. Multivariate analysis showed that a lower initial haemoglobin concentration was also independently associated with recurrence. Both regimens were well tolerated and no serious adverse events were reported. Conclusions Chloroquine remains an efficacious treatment for the treatment of vivax malaria in Afghanistan. In a setting where radical

  11. Autoshaping, random control, and omission training in the rat.

    Science.gov (United States)

    Locurto, C; Terrace, H S; Gibbon, J

    1976-11-01

    The role of the stimulus-reinforcer contingency in the development and maintenance of lever contact responding was studied in hooded rats. In Experiment I, three groups of experimentally naive rats were trained either on autoshaping, omission training, or a random-control procedure. Subjects trained by the autoshaping procedure responded more consistently than did either random-control or omission-trained subjects. The probability of at least one lever contact per trial was slightly higher in subjects trained by the omission procedure than by the random-control procedure. However, these differences were not maintained during extended training, nor were they evident in total lever-contact frequencies. When omission and random-control subjects were switched to the autoshaping condition, lever contacts increased in all animals, but a pronounced retardation was observed in omission subjects relative to the random-control subjects. In addition, subjects originally exposed to the random-control procedure, and later switched to autoshaping, acquired more rapidly than naive subjects that were exposed only on the autoshaping procedure. In Experiment II, subjects originally trained by an autoshaping procedure were exposed either to an omission, a random-control, or an extinction procedure. No differences were observed among the groups either in the rate at which lever contacts decreased or in the frequency of lever contacts at the end of training. These data implicate prior experience in the interpretation of omission-training effects and suggest limitations in the influence of stimulus-reinforcer relations in autoshaping.

  12. 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.

  13. Prospective, naturalistic study of open-label OROS methylphenidate treatment in Chinese school-aged children with attention-deficit/hyperactivity disorder

    Institute of Scientific and Technical Information of China (English)

    ZHENG Yi; GONG Mei-en; YIN Qing-yun; MAI Jian-ning; JING Jin; LUO Xiang-yang; MA Hong-wei; LI Hai-bo; XIE Ling; LI Yan; Kuang Gui-fang; WANG Yu-feng; YI Ming-ji; WANG Feng; ZHU Xiao-hua; YAO Yah-bin; QIN Jiong; WANG Li-wen; ZOU Li-ping; JIN Xing-ming; XU Tong; WANG Yi; QI Yuan-li

    2011-01-01

    Background Attention deficit hyperactivity disorder (ADHD) is one of the most common mental disorders during childhood,characterized by the core symptoms of hyperactivity,impulsivity and inattention and puts great burden on children themselves,their families and the society.Osmotic release oral system methylphenidate (OROS-MPH) is a once-daily controlled-release formulation developed to overcome some of the limitations associated with immediate-release methylphenidate (IR-MPH).It has been marketed in China since 2005 but still lacks data from large-sample clinical trials on efficacy and safety profiles.The aim of this study was to evaluate the effectiveness and safety of OROS-MPH in children aged 6 to 16 years with ADHD under naturalistic clinical setting.Methods This 6-week,multi-center,prospective,open-label study enrolled 1447 ADHD children to once-daily OROS-MPH (18 mg,36 mg or 54 mg) treatment.The effectiveness measures were parent-rated Inattention and Overactivity With Aggression (IOWA) Conners I/O and O/D subscales,physician-rated CGI-I and parent-rated global efficacy assessment scale.Blood pressure,pulse rate measurement,adverse events (AEs) and concomitant medications and treatment review were conducted by the investigator and were served as safety measures.Results A total of 1447 children with ADHD (mean age (9.52±2.36) years) were enrolled in this trial.Totally 96.8%children received an OROS-MPH modal dose of 18 mg,3.1% with 36 mg and 0.1% with 54 mg at the endpoint of study.The parent IOWA Conners I/O score at the end of week 2 showed statistically significant (P <0.001) improvement with OROS-MPH (mean:6.95±2.71) versus the score at baseline (10.45±2.72).The change in the parent IOWA Conners O/D subscale,CGI-I and parent-rated global efficacy assessment scale also supported the superior efficacy for OROS-MPH treatment.Fewer than half of 1447 patients (511 (35.3%)) reported AEs,and the majority of the events reported were mild (68.2

  14. Safety and tolerability of varenicline tartrate (Champix(®)/Chantix(®)) for smoking cessation in HIV-infected subjects: a pilot open-label study.

    Science.gov (United States)

    Cui, Qu; Robinson, Linda; Elston, Dawn; Smaill, Fiona; Cohen, Jeffrey; Quan, Corinna; McFarland, Nancy; Thabane, Lehana; McIvor, Andrew; Zeidler, Johannes; Smieja, Marek

    2012-01-01

    The prevalence of smoking in HIV-infected subjects is high. As a smoking cessation aid, varenicline (Champix(®), Pfizer, Saint-Laurent, QC, Canada or Chantix(®), Pfizer, Mission, KS) has not been previously evaluated in HIV-infected smokers. In this multicenter pilot open label study, varenicline 1.0 mg was used twice daily for 12 weeks with dose titration in the first week. Adverse events (AEs) during the treatment period were recorded. Changes from baseline in laboratory tests, vital signs, daily cigarette consumption, nicotine dependence, and withdrawal were measured through week 24. Self-reported abstinence was validated by serum cotinine at week 12. We enrolled 36 subjects with a mean of 29 pack-years of smoking and a minimum of 4 cigarettes per day. All but 1 were male, 33 (92%) were white. The most frequently reported AEs were nausea (33%), abnormal dreams (31%), affect lability (19%), and insomnia (19%). Six (17%) subjects discontinued varenicline due to AEs. No grade 3/4 laboratory abnormalities or serious AEs occurred during the study. There was no significant change in HIV viral load. CD4 counts increased by 69 cells/mm3 (p = 0.001) at week 24. Serum cotinine-verified 4-week continuous abstinence rate through weeks 9-12 was 42% (95% confidence interval [CI]: 26-58%). AEs and abstinence rates were comparable to those in published randomized controlled trials conducted in generally healthy HIV-negative smokers. Varenicline was safe and appears effective among HIV-infected smokers in this exploratory study, although AEs were common. The most common AE was nausea, with no adverse effect on HIV treatment outcome. Close monitoring of liver enzymes and blood pressure is recommended for HIV-positive smokers taking varenicline.

  15. Safety and Tolerability of Varenicline Tartrate (Champix®/Chantix®) for Smoking Cessation in HIV-Infected Subjects: A Pilot Open-Label Study

    Science.gov (United States)

    Robinson, Linda; Elston, Dawn; Smaill, Fiona; Cohen, Jeffrey; Quan, Corinna; McFarland, Nancy; Thabane, Lehana; McIvor, Andrew; Zeidler, Johannes; Smieja, Marek

    2012-01-01

    Abstract The prevalence of smoking in HIV-infected subjects is high. As a smoking cessation aid, varenicline (Champix®, Pfizer, Saint-Laurent, QC, Canada or Chantix®, Pfizer, Mission, KS) has not been previously evaluated in HIV-infected smokers. In this multicenter pilot open label study, varenicline 1.0 mg was used twice daily for 12 weeks with dose titration in the first week. Adverse events (AEs) during the treatment period were recorded. Changes from baseline in laboratory tests, vital signs, daily cigarette consumption, nicotine dependence, and withdrawal were measured through week 24. Self-reported abstinence was validated by serum cotinine at week 12. We enrolled 36 subjects with a mean of 29 pack-years of smoking and a minimum of 4 cigarettes per day. All but 1 were male, 33 (92%) were white. The most frequently reported AEs were nausea (33%), abnormal dreams (31%), affect lability (19%), and insomnia (19%). Six (17%) subjects discontinued varenicline due to AEs. No grade 3/4 laboratory abnormalities or serious AEs occurred during the study. There was no significant change in HIV viral load. CD4 counts increased by 69 cells/mm3 (p=0.001) at week 24. Serum cotinine-verified 4-week continuous abstinence rate through weeks 9–12 was 42% (95% confidence interval [CI]: 26–58%). AEs and abstinence rates were comparable to those in published randomized controlled trials conducted in generally healthy HIV-negative smokers. Varenicline was safe and appears effective among HIV-infected smokers in this exploratory study, although AEs were common. The most common AE was nausea, with no adverse effect on HIV treatment outcome. Close monitoring of liver enzymes and blood pressure is recommended for HIV-positive smokers taking varenicline. PMID:22007690

  16. Effect of nasal balloon autoinflation in children with otitis media with effusion in primary care: an open randomized controlled trial

    Science.gov (United States)

    Williamson, Ian; Vennik, Jane; Harnden, Anthony; Voysey, Merryn; Perera, Rafael; Kelly, Sadie; Yao, Guiqing; Raftery, James; Mant, David; Little, Paul

    2015-01-01

    Background: Otitis media with effusion is a common problem that lacks an evidence-based nonsurgical treatment option. We assessed the clinical effectiveness of treatment with a nasal balloon device in a primary care setting. Methods: We conducted an open, pragmatic randomized controlled trial set in 43 family practices in the United Kingdom. Children aged 4–11 years with a recent history of ear symptoms and otitis media with effusion in 1 or both ears, confirmed by tympanometry, were allocated to receive either autoinflation 3 times daily for 1–3 months plus usual care or usual care alone. Clearance of middle-ear fluid at 1 and 3 months was assessed by experts masked to allocation. Results: Of 320 children enrolled, those receiving autoinflation were more likely than controls to have normal tympanograms at 1 month (47.3% [62/131] v. 35.6% [47/132]; adjusted relative risk [RR] 1.36, 95% confidence interval [CI] 0.99 to 1.88) and at 3 months (49.6% [62/125] v. 38.3% [46/120]; adjusted RR 1.37, 95% CI 1.03 to 1.83; number needed to treat = 9). Autoinflation produced greater improvements in ear-related quality of life (adjusted between-group difference in change from baseline in OMQ-14 [an ear-related measure of quality of life] score −0.42, 95% CI −0.63 to −0.22). Compliance was 89% at 1 month and 80% at 3 months. Adverse events were mild, infrequent and comparable between groups. Interpretation: Autoinflation in children aged 4–11 years with otitis media with effusion is feasible in primary care and effective both in clearing effusions and improving symptoms and ear-related child and parent quality of life. Trial registration: ISRCTN, No. 55208702. PMID:26216608

  17. Effects of traditional cupping therapy in patients with carpal tunnel syndrome: a randomized controlled trial.

    Science.gov (United States)

    Michalsen, Andreas; Bock, Silke; Lüdtke, Rainer; Rampp, Thomas; Baecker, Marcus; Bachmann, Jürgen; Langhorst, Jost; Musial, Frauke; Dobos, Gustav J

    2009-06-01

    We investigated the effectiveness of cupping, a traditional method of treating musculoskeletal pain, in patients with carpal tunnel syndrome (CTS) in an open randomized trial. n = 52 outpatients (58.5 +/- 8.0 years) with neurologically confirmed CTS were randomly assigned to either a verum (n = 26) or a control group (n = 26). Verum patients were treated with a single application of wet cupping, and control patients with a single local application of heat within the region overlying the trapezius muscle. Patients were followed up on day 7 after treatment. The primary outcome, severity of CTS symptoms (VAS), was reduced from 61.5 +/- 20.5 to 24.6 +/- 22.7 mm at day 7 in the cupping group and from 67.1 +/- 20.2 to 51.7 +/- 23.9 mm in the control group [group difference -24.5mm (95%CI -36.1; -2.9, P cupping therapy may be effective in relieving the pain and other symptoms related to CTS. The efficacy of cupping in the long-term management of CTS and related mechanisms remains to be clarified. The results of a randomized trial on the clinical effects of traditional cupping therapy in patients with carpal tunnel syndrome are presented. Cupping of segmentally related shoulder zones appears to alleviate the symptoms of carpal tunnel syndrome.

  18. CERN opens up its control rooms to youngsters

    CERN Multimedia

    CERN Bulletin

    2011-01-01

    CERN is inviting 13 to 18 year-olds to come and spend a couple of hours in the control rooms of the LHC and its experiments. Registration is now open.   Is your neighbour's kid eager to come and see what's going on in the CERN control rooms for himself? Is your niece from Germany fascinated by the famous accelerator near Geneva that she's heard about and asking to know more? Then Researchers Night is for them! From 6.00 p.m. on Friday 23 September until 1.00 a.m. the following morning, the LHC and its experiments will open their doors to 13 to 18 year-olds. They are invited to come and spend a couple of hours in the control rooms watching the physicists and taking part in various activities. ALICE, ATLAS, CMS, LHCb, TOTEM, and the CERN Control Centre (CCC) will all be welcoming visitors. For this second year of CERN's involvement in European Researchers Night, the CERN exhibitions will be open late and special activities will be organised in Microcosm....

  19. Boosted PWM open loop control of hydraulic proportional valves

    International Nuclear Information System (INIS)

    Amirante, R.; Innone, A.; Catalano, L.A.

    2008-01-01

    This paper presents an innovative open loop control technique for direct single stage hydraulic proportional valves whose response rate is significantly higher than that obtained by standard open loop control techniques, even comparable to more costly commercial closed loop systems. Different from standard open loop techniques, which provide the coil with a constant current proportional to the target position, the control strategy proposed in this paper employs the peak and hold (P and H) technique, widely used in Diesel engine modern supply systems, to boost the duty cycle value of the pulse width modulation (PWM) signal for a short time, namely during the spool displacement, while maintaining a lower duty cycle for holding the spool in the required opening position. The developed 'boosted PWM' technique only requires a low cost microcontroller, such as a peripheral interface controller (PIC) equipped with a metal oxide semiconductor (MOS) power driver. The PWM parameters are calibrated as a function of the spool displacement so as to maximize the response rate without introducing overshoots: the collected data are stored in the PIC. Different valve opening procedures with step response have been compared to demonstrate the merits of the proposed boosted PWM technique. No overshoots have been registered. Moreover, the proposed method is characterized by a significantly higher response rate with respect to a standard open loop control, which approximately has the same cost. Similar experimental tests show that the proposed boosted PWM technique has a response rate even higher than that provided by the more costly commercial closed loop system mounted on the valve, and it produces no overshoots

  20. Boosted PWM open loop control of hydraulic proportional valves

    Energy Technology Data Exchange (ETDEWEB)

    Amirante, R.; Catalano, L.A. [Dipartimento di Ingegneria Meccanica e Gestionale, Politecnico di Bari, Via Re David 200, 70125 Bari (Italy); Innone, A. [Universita degli Studi di Foggia, via Napoli, 25 Foggia (Italy)

    2008-08-15

    This paper presents an innovative open loop control technique for direct single stage hydraulic proportional valves whose response rate is significantly higher than that obtained by standard open loop control techniques, even comparable to more costly commercial closed loop systems. Different from standard open loop techniques, which provide the coil with a constant current proportional to the target position, the control strategy proposed in this paper employs the peak and hold (P and H) technique, widely used in Diesel engine modern supply systems, to boost the duty cycle value of the pulse width modulation (PWM) signal for a short time, namely during the spool displacement, while maintaining a lower duty cycle for holding the spool in the required opening position. The developed 'boosted PWM' technique only requires a low cost microcontroller, such as a peripheral interface controller (PIC) equipped with a metal oxide semiconductor (MOS) power driver. The PWM parameters are calibrated as a function of the spool displacement so as to maximize the response rate without introducing overshoots: the collected data are stored in the PIC. Different valve opening procedures with step response have been compared to demonstrate the merits of the proposed boosted PWM technique. No overshoots have been registered. Moreover, the proposed method is characterized by a significantly higher response rate with respect to a standard open loop control, which approximately has the same cost. Similar experimental tests show that the proposed boosted PWM technique has a response rate even higher than that provided by the more costly commercial closed loop system mounted on the valve, and it produces no overshoots. (author)