Population pharmacokinetics and dosing regimen design of milrinone in preterm infants

Science.gov (United States)

Paradisis, Mary; Jiang, Xuemin; McLachlan, Andrew J; Evans, Nick; Kluckow, Martin; Osborn, David

2007-01-01

Aims To define the pharmacokinetics of milrinone in very preterm infants and determine an optimal dose regimen to prevent low systemic blood flow in the first 12 h after birth. Methods A prospective open‐labelled, dose‐escalation pharmacokinetic study was undertaken in two stages. In stage one, infants received milrinone at 0.25 μg/kg/min (n = 8) and 0.5 μg/kg/min (n = 11) infused from 3 to 24 h of age. Infants contributed 4–5 blood samples for concentration–time data which were analysed using a population modelling approach. A simulation study was used to explore the optimal dosing regimen to achieve target milrinone concentrations (180–300 ng/ml). This milrinone regimen was evaluated in stage two (n = 10). Results Infants (n = 29) born before 29 weeks gestation were enrolled. Milrinone pharmacokinetics were described using a one‐compartment model with first‐order elimination rate, with a population mean clearance (CV%) of 35 ml/h (24%) and volume of distribution of 512 ml (21%) and estimated half‐life of 10 h. The 0.25 and 0.5 μg/kg/min dosage regimens did not achieve optimal milrinone concentration‐time profiles to prevent early low systemic blood flow. Simulation studies predicted a loading infusion (0.75 μg/kg/min for 3 h) followed by maintenance infusion (0.2 μg/kg/min until 18 h of age) would provide an optimal milrinone concentration profile. This was confirmed in stage two of the study. Conclusion Population pharmacokinetic modelling in the preterm infant has established an optimal dose regimen for milrinone that increases the likelihood of achieving therapeutic aims and highlights the importance of pharmacokinetic studies in neonatal clinical pharmacology. PMID:16690639

Revisiting Dosing Regimen Using Pharmacokinetic/Pharmacodynamic Mathematical Modeling: Densification and Intensification of Combination Cancer Therapy.

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Meille, Christophe; Barbolosi, Dominique; Ciccolini, Joseph; Freyer, Gilles; Iliadis, Athanassios

2016-08-01

Controlling effects of drugs administered in combination is particularly challenging with a densified regimen because of life-threatening hematological toxicities. We have developed a mathematical model to optimize drug dosing regimens and to redesign the dose intensification-dose escalation process, using densified cycles of combined anticancer drugs. A generic mathematical model was developed to describe the main components of the real process, including pharmacokinetics, safety and efficacy pharmacodynamics, and non-hematological toxicity risk. This model allowed for computing the distribution of the total drug amount of each drug in combination, for each escalation dose level, in order to minimize the average tumor mass for each cycle. This was achieved while complying with absolute neutrophil count clinical constraints and without exceeding a fixed risk of non-hematological dose-limiting toxicity. The innovative part of this work was the development of densifying and intensifying designs in a unified procedure. This model enabled us to determine the appropriate regimen in a pilot phase I/II study in metastatic breast patients for a 2-week-cycle treatment of docetaxel plus epirubicin doublet, and to propose a new dose-ranging process. In addition to the present application, this method can be further used to achieve optimization of any combination therapy, thus improving the efficacy versus toxicity balance of such a regimen.

Evening versus morning dosing regimen drug therapy for chronic kidney disease patients with hypertension in blood pressure patterns: a systematic review and meta-analysis.

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Wang, Caixia; Ye, Yuqiu; Liu, Chunyong; Zhou, Yongming; Lv, Linsheng; Cheng, Cailian; Li, Shaomin; Lou, Tanqi; Liu, Xun

2017-08-01

Evening dosing regimen drug therapy on blood pressure (BP) control is used widely, but its clinical benefits and preservation or re-establishment of the normal 24-h BP dipping pattern in chronic kidney disease (CKD) patients is not known. To investigate the effect of an evening dosing regimen of antihypertensive drugs on BP patterns of CKD patients with hypertension. A systematic review was conducted by searching PUBMED, EMBASE, ASN-ONLINE, the Cochrane Library and the reference lists of relevant articles of published papers. All trials designed to evaluate the effects of evening versus morning dosing regimen drug therapy for CKD patients with hypertension were included. Meta-analysis was performed using random or fixed effects models. Five randomised controlled trials and one comparative study, including 3732 patients, met the inclusion criteria. Compared with morning dosing regimen drug therapy, evening administration of antihypertensive medication was associated with a significant reduction of 40% in non-dipper BP patterns (risk ratio (RR), 95% CI, (0.43, 0.84)). We noted a significant decrease in nocturnal systolic blood pressure (SBP) (MD -3.17 mmHg, 95% CI (-5.41, -0.94)), a significant reduction in nocturnal diastolic blood pressure (DBP) (MD -1.37 mmHg, 95% CI (-2.05, -0.69)) and a significant increase in awake SBP (MD 1.15 mmHg, 95% CI (0.10, 2.19)) in patients assigned to the evening dosing regimen drug therapy group. Patients showed no significant differences for all-cause mortality and cardiovascular mortality. This review shows that evening dosing regimen drug therapy could reverse non-dipper BP patterns in hypertensive CKD patients. © 2017 Royal Australasian College of Physicians.

Comparison of evening and morning dosing of travoprost 0.004%/timolol 0.5% fixed combination in 6 month period.

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Suić, Smiljka Popović; Laus, Katia Novak; Dosen, Vukosava Maricic; Ekert, Miroslav; Mandić, Zdravko; Bojić, Lovro

2010-09-01

An open label, multi-center, 6 months observational study of new fixed combination (travoprost 0.004%/timolol 0.5%), in order to evaluate both efficacy (intraocular pressure lowering) and tolerability (patient and investigator satisfaction) of two dosing regimens--evening (PM) and morning (AM). After screening for enrollment, to 40 patients (79 eyes with primary open angle glaucoma or ocular hypertension), new fixed combination travoprost 0.004%/timolol 0.5% was prescribed once a day in the evening (PM). Patients were enrolled according to each investigator decision on indication for travoprost 0.004%/timolol 0.5% fixed combination once a day, without washout period after previous medication. Intraocular pressure was measured at 9 AM at all time control points: at baseline, after 1 month, after 3 months and after 6 month. After 1 month, screening for nonresponders (criteria: 20% intraocular pressure lowering) and subjects with major side effects was performed. At second control visit, after 3 months PM dosing, intraocular pressure was measured and patients were instructed to continue once a day the same medication, but in the morning (AM) for consequent 3 months. After 1 month, reduction in mean intraocular pressure value was 21.66%. At the visit after 3 month, the mean intraocular pressure was 15.67 +/- 2.17 mm Hg (reduction 21.14%). 3 month after dosing regimen changed to AM (6 month after beginning of travoprost 0.004%/timolol 0.5% combination therapy), reduction in intraocular pressure value was 19.86%. The differences (mean +/- standard deviation) in intraocular pressure values after 1, 3 and 6 month were all highly statistically significant compared to baseline values. The tolerability was evaluated in five steps (Likert scale) ranging from unsatisfactory to excellent by both patient and investigator--taken at 3 and 6 month control visit. 95% of patients and 100% of investigators were satisfied with the possibility of choosing dosing regimen for travoprost 0

Body friendly, safe and effective regimen of MgSO4 for eclampsia

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Gautam S. Aher, Urmila Gavali

2013-01-01

Full Text Available Pre-eclampsia and eclampsia are major health problems in developing countries. MgSO4 is the standard drug in the control of convulsions in eclampsia. Our study carried out at PDVVPF’s hospital is based on the low dose regimen than Pritchard, which is suitable for Indian women who are of smaller built thanwomen in western world. This prospective study included 50 eclampsia patients receiving low dose MgSO4 therapy. The loading dose of MgSO4 was 9gm. Following this 2.5 gm was given intramuscularly every 6 hourly for 24 hours after administration of the loading dose. Patients were monitored hourly by observing their respiratory rate, knee jerk and urine output. Out of 50, two patients required Pritchard regimen, rest completely recovered from eclampsia. The maternal and perinatal morbidity and mortality were comparable to those of the standard Pritchard regime. The study did not find a single case of magnesium related toxicity with low dose MgSO4 regime. Low dose magnesium sulphate regime was found to be safe and effective in eclampsia

8-MOP PUVA for psoriasis: a comparison of a minimal phototoxic dose-based regimen with a skin-type approach

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Collins, P.; Wainwright, N.J.; Amorim, I.; Lakshmipathi, T.; Ferguson, J. [Ninewells Hospital and Medical School, Dundee (United Kingdom)

1996-08-01

Two ultraviolet A (UVA) regimens for oral 8-methoxypsoralen (8-MOP) photochemotherapy (PUVA) for moderate/severe chronic plaque psoriasis using a half-body study technique were compared. Each patient received both regimens. A higher-dose regimen based on minimal phototoxic dose (MPD) with percentage incremental increases was given to one-half of the body. The other half received a lower dose regimen based on skin type with fixed incremental UVA increases. Patients were treated twice weekly. Symmetrical plaques were scored to determine the rate of resolution with each regimen. In addition, the number of treatments, cumulative UVA dose and number of days in treatment to achieve overall clearance were recorded. Patients were reviewed monthly for one year to record remission data. Thirty-three patients completed the study. Both regimens were effective and well tolerated. With the MPD-based approach, number of exposures was significantly less for patients with skin types I and II but not III. Although the cumulative UVA dose was higher with the MPD regimen for all skin types studied, the reduced number of exposures required for clearance for skin types I and II but not III, combined with the security of individualized MPD testing, has practical attractions. MPD testing also identified five patients who required an increased psoralen dose and six patients who required a reduction of the initial UVA dose with the skin type regimen. Forty-two percent were still clear 1 year after treatment and there was no significant difference in the number of days in remission between the regimens for those whose psoriasis had recurred. The reduction in the number of exposures required for clearance with the MPD-based regimen may be safer and more cost effective in the long term. (author).

Efficacy and safety of a fixed dose artesunate-sulphamethoxypyrazine-pyrimethamine compared to artemether-lumefantrine for the treatment of uncomplicated falciparum malaria across Africa: a randomized multi-centre trial

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Djimdé Abdoulaye

2009-04-01

Full Text Available Abstract Background The efficacy of artemisinin-based combination therapy has already been demonstrated in a number of studies all over the world, and some of them can be regarded as comparably effective. Ease of administration of anti-malarial treatments with shorter courses and fewer tablets may be key determinant of compliance. Methods Patients with uncomplicated falciparum malaria and over six months of age were recruited in Cameroon, Mali, Rwanda and Sudan. 1,384 patients were randomly assigned to receive artesunate-sulphamethoxypyrazine-pyrimethamine (AS-SMP three-day (once daily for 3 days regimen (N = 476 or AS-SMP 24-hour (0 h, 12 h, 24 h regimen (N = 458 or artemether-lumefantrine (AL, the regular 6 doses regimen (N = 450. The primary objective was to demonstrate non-inferiority (using a margin of -6% of AS-SMP 24 hours or AS-SMP three days versus AL on the PCR-corrected 28-day cure rate. Results The PCR corrected 28-day cure rate on the intention to treat (ITT analysis population were: 96.0%(457/476 in the AS-SMP three-day group, 93.7%(429/458 in the AS-SMP 24-hour group and 92.0%(414/450 in the AL group. Likewise, the cure rates on the PP analysis population were high: 99.3%(432/437 in the AS-SMP three-day group, 99.5%(416/419 in the AS-SMP 24-hour group and 99.7(391/394% in the AL group. Most common drug-related adverse events were gastrointestinal symptoms (such as vomiting and diarrhea which were slightly higher in the AS-SMP 24-hour group. Conclusion AS-SMP three days or AS-SMP 24 hours are safe, are as efficacious as AL, and are well tolerated. Trial registration NCT00484900 http://www.clinicaltrials.gov.

Safety and pharmacokinetic profile of fixed-dose ivermectin with an innovative 18mg tablet in healthy adult volunteers.

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Jose Muñoz

2018-01-01

Full Text Available Ivermectin is a pivotal drug for the control of onchocerciasis and lymphatic filariasis, which is increasingly identified as a useful drug for the control of other Neglected Tropical Diseases. Its role in the treatment of soil transmitted helminthiasis through improved efficacy against Trichuris trichiura in combination with other anthelmintics might accelerate the progress towards breaking transmission. Ivermectin is a derivative of Avermectin B1, and consists of an 80:20 mixture of the equipotent homologous 22,23 dehydro B1a and B1b. Pharmacokinetic characteristics and safety profile of ivermectin allow to explore innovative uses to further expand its utilization through mass drug administration campaigns to improve coverage rates. We conducted a phase I clinical trial with 54 healthy adult volunteers who sequentially received 2 experimental treatments using a new 18 mg ivermectin tablet in a fixed-dose strategy of 18 and 36 mg single dose regimens, compared to the standard, weight based 150–200 μg/kg, regimen. Volunteers were recruited in 3 groups based on body weight. Plasma concentrations of ivermectin were measured through HPLC up to 168 hours post treatment. Safety data showed no significant differences between groups and no serious adverse events: headache was the most frequent adverse event in all treatment groups, none of them severe. Pharmacokinetic parameters showed a half-life between 81 and 91 h in the different treatment groups. When comparing the systemic bioavailability (AUC0t and Cmax of the reference product (WA-ref with the other two study groups using fixed doses, we observed an overall increase in AUC0t and Cmax for the two experimental treatments of 18 mg and 36 mg. Body mass index (BMI and weight were associated with t1/2 and V/F, probably reflecting the high liposolubility of IVM with longer retention times proportional to the presence of more adipose tissue. Systemic exposure to ivermectin (AUC0t or Cmax was not

Evidence-Based Design of Fixed-Dose Combinations: Principles and Application to Pediatric Anti-Tuberculosis Therapy.

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Svensson, Elin M; Yngman, Gunnar; Denti, Paolo; McIlleron, Helen; Kjellsson, Maria C; Karlsson, Mats O

2018-05-01

Fixed-dose combination formulations where several drugs are included in one tablet are important for the implementation of many long-term multidrug therapies. The selection of optimal dose ratios and tablet content of a fixed-dose combination and the design of individualized dosing regimens is a complex task, requiring multiple simultaneous considerations. In this work, a methodology for the rational design of a fixed-dose combination was developed and applied to the case of a three-drug pediatric anti-tuberculosis formulation individualized on body weight. The optimization methodology synthesizes information about the intended use population, the pharmacokinetic properties of the drugs, therapeutic targets, and practical constraints. A utility function is included to penalize deviations from the targets; a sequential estimation procedure was developed for stable estimation of break-points for individualized dosing. The suggested optimized pediatric anti-tuberculosis fixed-dose combination was compared with the recently launched World Health Organization-endorsed formulation. The optimized fixed-dose combination included 15, 36, and 16% higher amounts of rifampicin, isoniazid, and pyrazinamide, respectively. The optimized fixed-dose combination is expected to result in overall less deviation from the therapeutic targets based on adult exposure and substantially fewer children with underexposure (below half the target). The development of this design tool can aid the implementation of evidence-based formulations, integrating available knowledge and practical considerations, to optimize drug exposures and thereby treatment outcomes.

A randomized comparative trial of two low-dose oral isotretinoin regimens in moderate to severe acne vulgaris

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Dhaked, Daulat Ram; Meena, Ram Singh; Maheshwari, Anshul; Agarwal, Uma Shankar; Purohit, Saroj

2016-01-01

Background: Oral isotretinoin is highly effective in all forms and grades of acne, even in lower dosages (acne vulgaris. Materials and Methods: A total of 240 patients with moderate to severe acne vulgaris were selected and randomized into two groups and treated with a fixed dose of 20 mg of isotretinoin (Group A - daily and Group B - alternate days) for 24 weeks and followed up for 12 weeks post therapy. Results: A total of 234 patients completed the study. At the end of therapy, decrease in the total acne loads up to 98.99% (Group A) and 97.69% (Group B) was achieved from the baseline (P acne, Group A performed significantly better than Group B until the end of 36 weeks. While in the moderate acne, significant difference in the response between both groups was observed only up to 12 weeks. No serious side effect was observed. Conclusion: Both isotretinoin regimens were well tolerated and found to be an effective treatment for moderate to severe acne vulgaris. However, in moderate acne 20 mg alternate day regimen may be preferred. A 20 mg daily regimen is a better choice for severe acne in terms of response. Limitation: Small sample size and short follow-up period. PMID:27730033

Treatment of hyperthyroidism with fixed dose form Iodine 131

International Nuclear Information System (INIS)

Pacheco Torres, P.; Cerquera, A.M.; Acosta, F.; Sierra, M.

2007-01-01

Full text: Objective: Evaluation of the response to therapy with fixed dose of Iodine-131 in patients with hyperthyroidism. One hundred seventeen patients with hyperthyroidism were tested and sent for treatment with Iodine-131. The dose of the therapy was calculated according to the pathology (Diffuser goiter (DG): Multinodular goiter (MNG) and Single toxic nodule (NST). Values of TSH confirmed hyperthyroidism by laboratory methods. The thyroid-blocking agents were discontinued: methimazole for five days and propylthiouracil two days prior to therapy. The pregnancy tests were routinely conducted in females of reproductive age group. Patients reported fasting for therapy. The doses were administered in capsule form after obtaining informed consent from the patients. The patients were normally instructed to eat only after two hours after administration of iodine to promote gastric absorption of the radionuclide. Normally a post therapy thyroid scan is performed four days after treatment. Patients are usually followed up by the endocrinologists. A three- month post therapy evaluation is done by the nuclear medicine physician by telephone. The demographic data of our patients treated are as follows: Total number of patients: 117 Female: 88 (75.21%) Male: 29 (24.79%) Age average: 45 years. Diffuse Goiter= 94 (80.34%), Multinodular Goiter= 17 (14.52%) and Toxic Adenoma (NST) = 6 (5.12%). The average administered dose was 22.5 mCi to DG, 41.8 mCi to MNG and 37.5 mCi to NST. 102 (87.14%) patients at the control at 2 years after treatment presented stable response to therapy, 15 (12.86%) required a second therapy, 11 (11.70%) with BD and 4 (23.52%) with BMN; and any patient with NST required a second therapy. 83 (88.29%) of the patients with BD; 13 (76.48%) with BMN and 6 (100%) with NST the therapy was successful. Conclusion: Fixed dose of I-131 in hyperthyroidism is useful in patients with DG (11.70%). In patients with MNG whom a fixed dose is supplied, 23.52% require a

The 24-hour intraocular pressure control by tafluprost/timolol fixed combination after switching from the concomitant use of tafluprost and timolol gel-forming solution, in patients with primary open-angle glaucoma

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Nakamoto K

2018-02-01

Full Text Available Kenji Nakamoto,1 Masahiko Takeshi,2 Toshihiko Hiraoka,2,3 Mayuko Eguchi,2,4 Yuichiro Nakano,1,2 Naomi Otsuka,5 Hiroko Hizaki,5 Hiromi Akai,5 Masayo Hashimoto5 1Department of Ophthalmology, Nippon Medical School, Tokyo, Japan; 2Shinanozaka Clinic, Tokyo, Japan; 3Hiraoka Eye Clinic, Saitama, Japan; 4Musashiurawa Eye Clinic, Saitama, Japan; 5Japan Medical Affairs, Global R&D, Santen Pharmaceutical Co., Ltd., Osaka, Japan Objective: The aim of this study was to evaluate the 24-hour intraocular pressure (IOP-control effect of the tafluprost/timolol fixed combination (TAF/TIM-FC in patients with primary open-angle glaucoma after they switched from the concomitant use of tafluprost and timolol gel-forming solution. Patients and methods: Twenty patients with primary open-angle glaucoma (12 male and 8 female; mean ± SD age, 57.0±7.1 years were included in this study. The patients were treated for 8 weeks with the concomitant administration of tafluprost and timolol gel-forming solution (evening dosing. At the end of this period, the patients underwent 24-hour IOP monitoring (measured at 21:00, 01:00, 05:00, 09:00, 13:00 and 17:00. IOP was measured with Goldmann applanation tonometer (GAT and Icare PRO at sitting position at all timepoints and additionally, at supine position with Icare PRO tonometer at 01:00 and 05:00. The patients were then all switched to TAF/TIM-FC treatment (evening dosing. After 8 weeks, the 24-hour IOP monitoring was repeated. Results: Nineteen patients completed the study. The mean 24-hour IOPs in the concomitant and TAF/TIM-FC phases were 13.8±2.7 vs 13.3±2.8 mmHg (P=0.0033 with the GAT in the sitting position and 13.96±2.56 vs 13.48±2.56 mmHg (P=0.0120 with the Icare PRO in habitual positions. In comparison with the concomitant phase, significantly lower IOP was observed for the TAF/TIM-FC phase at 21:00 and 01:00 with the GAT and at 01:00 with the Icare PRO. In addition, the maximum IOP and fluctuations in IOP in

Comparison of adherence to generic multi-tablet regimens vs. brand multi-tablet and brand single-tablet regimens likely to incorporate generic antiretroviral drugs by breaking or not fixed-dose combinations in HIV-infected patients.

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Rwagitinywa, Joseph; Lapeyre-Mestre, Maryse; Bourrel, Robert; Montastruc, Jean-Louis; Sommet, Agnès

2018-03-05

Adherence to antiretroviral (ARV) is crucial to achieve viral load suppression in HIV-infected patients. This study aimed to compare adherence to generic multi-tablet regimens (MTR) vs. brand MTR likely to incorporate ARV drugs without breaking fixed-dose combinations (FDC) and brand single-tablet regimens (STR) likely to incorporate generics by breaking the FDC. Patients aged of 18 years or over exposed to one of the generic or the brand of lamivudine (3TC), zidovudine/lamivudine (AZT/TC), nevirapine (NVP), or efavirenz (EFV), or the brand STR of efavirenz/emtricitabine/tenofovir (EFV/FTC/TDF). Adherence was measured by medication possession ratio (MPR) using both defined daily dose (DDD) and daily number of tablet recommended for adults (DNT). Adherence to generic MTR vs. brand MTR and brand STR was compared using Kruskal-Wallis. The overall median adherence was 0.97 (IQR 0.13) by DNT method and 0.97 (0.14) by DDD method. Adherence in patients exposed to generic MTR (n = 165) vs. brand MTR (n = 481) and brand STR (n = 470) was comparable by DNT and DDD methods. In conclusion, adherence to generic MTR was high and comparable with adherence to brand MTR and to STR. Utilization of DDD instead DNT to measure the MPR led to small but nonsignificant difference that has no clinical impact. © 2018 Société Française de Pharmacologie et de Thérapeutique.

Estimation of the optimal dosing regimen of escitalopram in dogs: A dose occupancy study with [11C]DASB.

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Olivia Taylor

Full Text Available Although the favourable characteristics of escitalopram as being the most selective serotonin reuptake inhibitor and having an increased therapeutic efficacy via binding on an additional allosteric binding site of the serotonin transporter, its dosing regimen has not yet been optimized for its use in dogs. This study aimed to estimate the optimal dosing frequency and the required dose for achieving 80% occupancy of the serotonin transporters in the basal ganglia. The dosing frequency was investigated by determining the elimination half-life after a four day oral pre-treatment period with 0.83 mg/kg escitalopram (3 administrations/day and a subsequent i.v. injection 0.83 mg/kg. Blood samples were taken up to 12 hours after i.v. injection and the concentration of escitalopram in plasma was analysed via LC-MSMS. The dose-occupancy relationship was then determined by performing two PET scans in five adult beagles: a baseline PET scan and a second scan after steady state conditions were achieved following oral treatment with a specific dose of escitalopram ranging from 0.5 to 2.5 mg/kg/day. As the elimination half-life was determined to be 6.7 hours a dosing frequency of three administrations a day was proposed for the second part of the study. Further it was opted for a treatment period of four days, which well exceeded the minimum period to achieve steady state conditions. The optimal dosing regimen to achieve 80% occupancy in the basal ganglia and elicit a therapeutic effect, was calculated to be 1.85 mg/kg/day, divided over three administrations. Under several circumstances, such as insufficient response to other SSRIs, concurrent drug intake or in research studies focused on SERT, the use of escitalopram can be preferred over the use of the already for veterinary use registered fluoxetine, however, in case of long-term treatment with escitalopram, regularly cardiac screening is recommended.

Estimation of the optimal dosing regimen of escitalopram in dogs: A dose occupancy study with [11C]DASB.

Science.gov (United States)

Taylor, Olivia; Van Laeken, Nick; Polis, Ingeborgh; Dockx, Robrecht; Vlerick, Lise; Dobbeleir, Andre; Goethals, Ingeborg; Saunders, Jimmy; Sadones, Nele; Baeken, Chris; De Vos, Filip; Peremans, Kathelijne

2017-01-01

Although the favourable characteristics of escitalopram as being the most selective serotonin reuptake inhibitor and having an increased therapeutic efficacy via binding on an additional allosteric binding site of the serotonin transporter, its dosing regimen has not yet been optimized for its use in dogs. This study aimed to estimate the optimal dosing frequency and the required dose for achieving 80% occupancy of the serotonin transporters in the basal ganglia. The dosing frequency was investigated by determining the elimination half-life after a four day oral pre-treatment period with 0.83 mg/kg escitalopram (3 administrations/day) and a subsequent i.v. injection 0.83 mg/kg. Blood samples were taken up to 12 hours after i.v. injection and the concentration of escitalopram in plasma was analysed via LC-MSMS. The dose-occupancy relationship was then determined by performing two PET scans in five adult beagles: a baseline PET scan and a second scan after steady state conditions were achieved following oral treatment with a specific dose of escitalopram ranging from 0.5 to 2.5 mg/kg/day. As the elimination half-life was determined to be 6.7 hours a dosing frequency of three administrations a day was proposed for the second part of the study. Further it was opted for a treatment period of four days, which well exceeded the minimum period to achieve steady state conditions. The optimal dosing regimen to achieve 80% occupancy in the basal ganglia and elicit a therapeutic effect, was calculated to be 1.85 mg/kg/day, divided over three administrations. Under several circumstances, such as insufficient response to other SSRIs, concurrent drug intake or in research studies focused on SERT, the use of escitalopram can be preferred over the use of the already for veterinary use registered fluoxetine, however, in case of long-term treatment with escitalopram, regularly cardiac screening is recommended.

47 CFR 80.705 - Hours of service of Alaska-public fixed stations.

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2010-10-01

... SPECIAL RADIO SERVICES STATIONS IN THE MARITIME SERVICES Alaska Fixed Stations § 80.705 Hours of service of Alaska-public fixed stations. Each Alaska-public fixed station whose hours of service are not... 47 Telecommunication 5 2010-10-01 2010-10-01 false Hours of service of Alaska-public fixed...

Efficacy and safety of weight-based insulin glargine dose titration regimen compared with glucose level- and current dose-based regimens in hospitalized patients with type 2 diabetes: a randomized, controlled study.

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Li, Xiaowei; Du, Tao; Li, Wangen; Zhang, Tong; Liu, Haiyan; Xiong, Yifeng

2014-09-01

Insulin glargine is widely used as basal insulin. However, published dose titration regimens for insulin glargine are complex. This study aimed to compare the efficacy and safety profile of a user-friendly, weight-based insulin glargine dose titration regimen with 2 published regimens. A total of 160 hospitalized patients with hyperglycemia in 3 medical centers were screened. Our inclusion criteria included age 18 to 80 years and being conscious. Exclusion criteria included pregnancy or breast-feeding and hepatic or renal dysfunction. A total of 149 patients were randomly assigned to receive weight-based, glucose level-based, or dose-based insulin glargine dose titration regimen between January 2011 and February 2013. The initial dose of insulin glargine was 0.2 U/kg. In the weight-based regimen (n = 49), the dose was titrated by increments of 0.1 U/kg daily. In the glucose level-based regimen (n = 51), the dose was titrated by 2, 4, 6, or 8 U daily when fasting blood glucose (FBG) was, respectively, between 7.0 and 7.9, 8.0 and 8.9, 9.0 and 9.9, or ≥10 mmol/L. In the current dose-based regimen (n = 49), titration was by daily increments of 20% of the current dose. The target FBG in all groups was ≤7.0 mmol/L. The incidence of hypoglycemia was recorded. One-way ANOVA and χ(2) test were used to compare data between the 3 groups. All but 1 patient who required additional oral antidiabetic medication completed the study. The mean (SD) time to achieve target FBG was 3.2 (1.2) days with the weight-based regimen and 3.7 (1.5) days with the glucose level-based regimen (P = 0.266). These times were both shorter than that achieved with the current dose-based regimen (4.8 [2.8] days; P = 0.0001 and P = 0.005, respectively). The daily doses of insulin glargine at the study end point were 0.43 (0.13) U/kg with the weight-based regimen, 0.50 (0.20) U/kg with the glucose level-based regimen, and 0.47 (0.23) U/kg with the current dose-based regimen (P = 0.184). The incidence

The 24-hour society between myth and reality.

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Costa, G

2001-12-01

The 24-hour society appears to be an ineluctable process towards a social organisation where time constraints are no more "restricting" the human life. But, what kind of 24-hour society do we need? At what costs? Are they acceptable/sustainable? Shift work, night work, irregular and flexible working hours, together with new technologies, are the milestone of this epochal passage, of which shift workers are builders and victims at the same time. The borders between working and social times are no more fixed and rigidly determined: not only the link between work place and working hours is broken, but also the value of working time changes according to the different economic/productive/social effects it can make. What are the advantages and disadvantages for the individual, the companies, and the society? What is the cost/benefit ratio in terms of physical health; psychological well-being, family and social life? The research on irregular working hours and health shows us what can be the negative consequences of non-human-centered working times organisations. Coping properly with this process means avoiding a passive acceptance of it with consequent maladjustments at both individual and social level, but adopting effective preventive and compensative strategies aimed at building a more sustainable society, at acceptable costs and with the highest possible benefits.

Spillover adherence effects of fixed-dose combination HIV therapy

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Kauf TL

2012-02-01

Full Text Available Teresa L Kauf1, Keith L Davis2, Stephanie R Earnshaw2, E Anne Davis31Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL, 2RTI Health Solutions, Research Triangle Park, NC, 3Independent consultant, Pittsboro, NC, USAAbstract: The impact of fixed-dose combination (FDC products on adherence to other, non-fixed regimen components has not been examined. We compared adherence to a third antiretroviral (ART component among patients receiving a nucleoside reverse transcriptase inhibitor (NRTI backbone consisting of the FDC Epzicom®, GlaxoSmithKline Inc, Research Triangle Park, NC (abacavir sulfate 600 mg + lamivudine 300 mg; FDC group versus NRTI combinations taken as two separate pills (NRTI Combo group using data from a national sample of 30 health plans covering approximately 38 million lives from 1997 to 2005. Adherence was measured as the medication possession ratio (MPR. Multivariate logistic regression compared treatment groups based on the likelihood of achieving ≥95% adherence, with sensitivity analyses using alternative thresholds. MPR was assessed as a continuous variable using multivariate linear regression. Covariates included age, gender, insurance payer type, year of study drug initiation, presence of mental health and substance abuse disorders, and third agent class. The study sample consisted of 650 FDC and 1947 NRTI Combo patients. Unadjusted mean adherence to the third agent was higher in the FDC group than the NRTI Combo group (0.92 vs 0.85; P < 0.0001. In regression analyses, FDC patients were 48% and 39% more likely to achieve 95% and 90% third agent adherence, respectively (P ≤ 0.03. None of the other MPR specifications achieved comparable results. Among managed care patients, use of an FDC appears to substantially improve adherence to a third regimen component and thus the likelihood of achieving the accepted standard for adherence to HIV therapy of 95%.Keywords

Non-24-Hour Sleep-Wake Disorder Revisited - A Case Study.

Science.gov (United States)

Garbazza, Corrado; Bromundt, Vivien; Eckert, Anne; Brunner, Daniel P; Meier, Fides; Hackethal, Sandra; Cajochen, Christian

2016-01-01

The human sleep-wake cycle is governed by two major factors: a homeostatic hourglass process (process S), which rises linearly during the day, and a circadian process C, which determines the timing of sleep in a ~24-h rhythm in accordance to the external light-dark (LD) cycle. While both individual processes are fairly well characterized, the exact nature of their interaction remains unclear. The circadian rhythm is generated by the suprachiasmatic nucleus ("master clock") of the anterior hypothalamus, through cell-autonomous feedback loops of DNA transcription and translation. While the phase length (tau) of the cycle is relatively stable and genetically determined, the phase of the clock is reset by external stimuli ("zeitgebers"), the most important being the LD cycle. Misalignments of the internal rhythm with the LD cycle can lead to various somatic complaints and to the development of circadian rhythm sleep disorders (CRSD). Non-24-hour sleep-wake disorders (N24HSWD) is a CRSD affecting up to 50% of totally blind patients and characterized by the inability to maintain a stable entrainment of the typically long circadian rhythm (tau > 24.5 h) to the LD cycle. The disease is rare in sighted individuals and the pathophysiology less well understood. Here, we present the case of a 40-year-old sighted male, who developed a misalignment of the internal clock with the external LD cycle following the treatment for Hodgkin's lymphoma (ABVD regimen, four cycles and AVD regimen, four cycles). A thorough clinical assessment, including actigraphy, melatonin profiles and polysomnography led to the diagnosis of non-24-hour sleep-wake disorders (N24HSWD) with a free-running rhythm of tau = 25.27 h. A therapeutic intervention with bright light therapy (30 min, 10,000 lux) in the morning and melatonin administration (0.5-0.75 mg) in the evening failed to entrain the free-running rhythm, although a longer treatment duration and more intense therapy might have

Correlation of 2 hour, 4 hour, 8 hour and 12 hour urine protein with 24 hour urinary protein in preeclampsia.

Directory of Open Access Journals (Sweden)

Savita Rani Singhal

2014-09-01

Full Text Available To find shortest and reliable time period of urine collection for determination of proteinuria.It is a prospective study carried out on 125 pregnant women with preeclampsia after 20 weeks of gestation having urine albumin >1 using dipstick test. Urine was collected in five different time intervals in colors labeled containers with the assistance of nursing staff; the total collection time was 24 hours. Total urine protein of two-hour, four-hour, eight-hour, 12-hour and 24-hour urine was measured and compared with 24-hour collection. Data was analyzed using the Pearson correlation coefficient.There was significant correlation (p value < 0.01 in two, four, eight and 12-hour urine protein with 24-urine protein, with correlation coefficient of 0.97, 0.97, 0.96 and 0.97, respectively. When a cut off value of 25 mg, 50 mg. 100 mg, and 150 mg for urine protein were used for 2-hour, 4-hours, 8-hour and 12-hour urine collection, a sensitivity of 92.45%, 95.28%, 91.51%, and 96.23% and a specificity of 68.42%, 94.74%, 84.21% and 84.21% were obtained, respectively.Two-hour urine proteins can be used for assessment of proteinuria in preeclampsia instead of gold standard 24-hour urine collection for early diagnosis and better patient compliance.

Characteristics of HIV antiretroviral regimen and treatment adherence

Directory of Open Access Journals (Sweden)

Vera Lúcia da Silveira

Full Text Available The relationship between characteristics of HIV antiretroviral regimens and treatment adherence was studied in adolescent and adult patients who underwent antiretroviral therapy from January 1998 to September 2000, at the Service for Specialized Assistance in Pelotas. The patients were interviewed on two occasions, and the use of antiretrovirals during the previous 48 hours was investigated by a self-report. Adherence was defined as use of 95% or more of the prescribed medication. Social-demographic variables were collected through direct questionnaires. The antiretroviral regimen and clinical data were copied from the patients' records. Associations between the independent variables and adherence were analyzed by means of logistic regression. The multivariate analysis included characteristics of the antiretroviral regimens, social-demographic variables, as well as perception of negative effects, negative physiological states, and adverse effects of the treatment. Among the 224 selected patients, 194 participated in our study. Their ages varied from 17 to 67 years; most patients were men, with few years of schooling and a low family income. Only 49% adhered to the treatment. Adherence to treatment regimens was reduced when more daily doses were indicated: three to four doses (odds ratio of adherence to treatment (OR=0.47, 95% confidence interval (CI 0.22-1.01 and five to six (OR=0.24, 95% CI 0.09-0.62; two or more doses taken in a fasting state (OR=0.59, 95% CI 0.11-0.68, and for patients who reported adverse effects to the treatment (OR=0.39, 95% CI 0.19-0.77. Most of the regimens with more than two daily doses of medication included at least one dose apart from mealtimes. The results suggest that, if possible, regimens with a reduced number of doses should be chosen, with no compulsory fasting, and with few adverse effects. Strategies to minimize these effects should be discussed with the patients.

Late effects of various dose-fractionation regimens

International Nuclear Information System (INIS)

Turesson, I.; Notter, G.

1983-01-01

These clinical investigations of various dose-fractionation regimens on human skin show that: The late reactions cannot be predicted from the early reactions; The dose-response curves for late reactions are much steeper than for early reactions; Equivalent doses for various fractionation schedules concerning late effects can be calculated by means of a corrected CRE (NSD) formula; the correction must be considered preliminary because further follow-up is needed. A clinical fractionation study of this type requires: Extremely careful dosimetry; Study of the same anatomical region; Very long follow-up; Studies at different effect levels; Skin reaction is the only end point we have studied systematically for different fractionation regimens. Experience with the CRE formula as a model for calculating isoeffect doses for different fractionation schedules in routine clinical use can be summarized as follows: The CRE formula has been used prospectively since 1972 in all patients; CRE-equivalent weekly doses to 5 x 2.0 Gy per week has been used. (Although the fractionation schedule is changed, the overall treatment time is still the same); The CRE range was 18 to 21 for curative radiotherapy on carcinomas; No irradiation was applied during pronounced acute reactions. No unexpected complications have been observed under these conditions

Pharmacokinetics of Pyrazinamide and Optimal Dosing Regimens for Drug-Sensitive and -Resistant Tuberculosis.

Science.gov (United States)

Chirehwa, Maxwell T; McIlleron, Helen; Rustomjee, Roxana; Mthiyane, Thuli; Onyebujoh, Philip; Smith, Peter; Denti, Paolo

2017-08-01

Pyrazinamide is used in the treatment of tuberculosis (TB) because its sterilizing effect against tubercle bacilli allows the shortening of treatment. It is part of standard treatment for drug-susceptible and drug-resistant TB, and it is being considered as a companion drug in novel regimens. The aim of this analysis was to characterize factors contributing to the variability in exposure and to evaluate drug exposures using alternative doses, thus providing evidence to support revised dosing recommendations for drug-susceptible and multidrug-resistant tuberculosis (MDR-TB). Pyrazinamide pharmacokinetic (PK) data from 61 HIV/TB-coinfected patients in South Africa were used in the analysis. The patients were administered weight-adjusted doses of pyrazinamide, rifampin, isoniazid, and ethambutol in fixed-dose combination tablets according to WHO guidelines and underwent intensive PK sampling on days 1, 8, 15, and 29. The data were interpreted using nonlinear mixed-effects modeling. PK profiles were best described using a one-compartment model with first-order elimination. Allometric scaling was applied to disposition parameters using fat-free mass. Clearance increased by 14% from the 1st day to the 29th day of treatment. More than 50% of patients with weight less than 55 kg achieved lower pyrazinamide exposures at steady state than the targeted area under the concentration-time curve from 0 to 24 h of 363 mg · h/liter. Among patients with drug-susceptible TB, adding 400 mg to the dose for those weighing 30 to 54 kg improved exposure. Average pyrazinamide exposure in different weight bands among patients with MDR-TB could be matched by administering 1,500 mg, 1,750 mg, and 2,000 mg to patients in the 33- to 50-kg, 51- to 70-kg, and greater than 70-kg weight bands, respectively. Copyright © 2017 American Society for Microbiology.

Multicentre evaluation of postoperative pain control after 24hours in three hospitals of Colombia.

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Machado-Alba, Jorge Enrique; Machado-Duque, Manuel Enrique; Ramírez-Sarmiento, Javier Orlando

To determine the intensity of pain in operated patients using a visual analogue scale and identify variables associated with lack of pain control in three cities in Colombia. A cross-sectional study in patients over the age of 18 years, between January 1 st and September 30 th 2014, in 3 clinics in Colombia. The intensity of postoperative pain using a visual analogue scale at 24hours after surgery was recorded. Socio-demographic, clinical and pharmacological variables were taken into account. SPSS 22.0 was used for the analysis. 460 patients were evaluated, mean age 47.6±17.4 years, and 63.3% were female. The mean pain level was 23.8±17.4mm, with 91 (19.8% of patients) with moderate or greater pain (i.e., lack of pain control). Tramadol was the most used analgesic, followed by dipyrone and diclofenac. 53.0% were treated with monotherapy. Compliance with the dosing regimen of the first analgesic (OR: 0.53; 95% CI: 0.294 to .988; p=.046) was statistically significantly associated with a decreased risk of poorly controlled pain. Pain intensity and the proportion of patients with uncontrolled pain at 24hours after surgery show better results than other studies previously published in the country. There must be insistence on the administration of analgesia within a suitable interval in order to improve pain control. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Atrial Fibrillation Detection During 24-Hour Ambulatory Blood Pressure Monitoring: Comparison With 24-Hour Electrocardiography.

Science.gov (United States)

Kollias, Anastasios; Destounis, Antonios; Kalogeropoulos, Petros; Kyriakoulis, Konstantinos G; Ntineri, Angeliki; Stergiou, George S

2018-07-01

This study assessed the diagnostic accuracy of a novel 24-hour ambulatory blood pressure (ABP) monitor (Microlife WatchBP O3 Afib) with implemented algorithm for automated atrial fibrillation (AF) detection during each ABP measurement. One hundred subjects (mean age 70.6±8.2 [SD] years; men 53%; hypertensives 85%; 17 with permanent AF; 4 paroxysmal AF; and 79 non-AF) had simultaneous 24-hour ABP monitoring and 24-hour Holter monitoring. Among a total of 6410 valid ABP readings, 1091 (17%) were taken in ECG AF rhythm. In reading-to-reading ABP analysis, the sensitivity, specificity, and accuracy of ABP monitoring in detecting AF were 93%, 87%, and 88%, respectively. In non-AF subjects, 12.8% of the 24-hour ABP readings indicated false-positive AF, of whom 27% were taken during supraventricular premature beats. There was a strong association between the proportion of false-positive AF readings and that of supraventricular premature beats ( r =0.67; P ABP monitoring had 100%/85% sensitivity/specificity (area under the curve 0.91; P ABP monitor with AF detector has high sensitivity and moderate specificity for AF screening during routine ABP monitoring. Thus, in elderly hypertensives, a 24-hour ABP recording with at least 26% of the readings suggesting AF indicates a high probability for AF diagnosis and should be regarded as an indication for performing 24-hour Holter monitoring. © 2018 American Heart Association, Inc.

Predictive tools for designing new insulins and treatment regimens

DEFF Research Database (Denmark)

Klim, Søren

The thesis deals with the development of "Predictive tools for designing new insulins and treatments regimens" and consists of two parts: A model based approach for bridging properties of new insulin analogues from glucose clamp experiments to meal tolerance tests (MTT) and a second part that des......The thesis deals with the development of "Predictive tools for designing new insulins and treatments regimens" and consists of two parts: A model based approach for bridging properties of new insulin analogues from glucose clamp experiments to meal tolerance tests (MTT) and a second part...... that describes an implemented software program able to handle stochastic differential equations (SDEs) with mixed effects. The thesis is supplemented with scientific papers published during the PhD. Developing an insulin analogue from candidate molecule to a clinical drug consists of a development programme...... and efficacy are investigated. Numerous methods are used to quantify dose and efficacy in Phase II - especially of interest is the 24-hour meal tolerance test as it tries to portray near normal living conditions. Part I describes an integrated model for insulin and glucose which is aimed at simulating 24-hour...

Phase II trial of weekly 24-hour infusion of gemcitabine in patients with advanced gallbladder and biliary tract carcinoma

International Nuclear Information System (INIS)

Delius, Stefan von; Lersch, Christian; Schulte-Frohlinde, Ewert; Mayr, Martina; Schmid, Roland M; Eckel, Florian

2005-01-01

Patients with advanced gallbladder and biliary tract carcinoma face a dismal prognosis, as no effective palliative chemotherapy exists. The antitumor effect of gemcitabine is schedule-dependent rather than dose-dependent. We evaluated the activity of a prolonged infusion of gemcitabine in advanced gallbladder and biliary tract carcinomas. Nineteen consecutive eligible patients were enrolled. All patients were required to have histologically confirmed diagnosis and measurable disease. Gemcitabine was infused over 24 hours at a dose of 100 mg/m 2 on days 1, 8, and 15. Treatment was repeated every 28 days until progression of disease or limiting toxicity. Tumor response was evaluated every second course by computed tomography (CT) scans. Eighteen patients were evaluable for response. A total of 89 cycles of therapy were administered. One partial response was observed (6%; 95% confidence interval (CI): 0–27%) and ten additional patients had stable disease for at least two months (disease control rate 61%; 95% CI: 36–83%). The therapy was well tolerated, with moderate myelosuppression as the main toxicity. The median time to tumor progression and median overall survival was 3.6 months (95% CI 2.6–4.6 months) and 7.5 months (95% CI 6.5–8.5 months), respectively. Weekly 24-hour gemcitabine at a dose of 100 mg/m 2 is well tolerated. There was a relatively high rate of disease control for a median duration of 5.3 months (range 2.8–18.8 months). However, the objective response rate of this regimen in gallbladder and biliary tract carcinomas was limited

Symptom-triggered benzodiazepine therapy for alcohol withdrawal syndrome in the emergency department: a comparison with the standard fixed dose benzodiazepine regimen.

LENUS (Irish Health Repository)

Cassidy, Eugene M

2012-10-01

The aim of the study was to compare symptom-triggered and standard benzodiazepine regimens for the treatment of alcohol withdrawal syndrome in an emergency department clinical decision unit. The authors found that the symptom-triggered approach reduced cumulative benzodiazepine dose and length of stay.

RESULTS OF LONG-TERM THERAPY WITH GROWTH-HORMONE IN 2 DOSE REGIMENS IN TURNER SYNDROME

NARCIS (Netherlands)

NIENHUIS, HE; RONGENWESTERLAKEN, C; WIT, JM; OTTEN, BJ; KEIZERSCHRAMA, SMPFD; DRAYER, NM; DELEMARREVANDEWAAL, HA; VULSMA, T; OOSTDIJK, W; WAELKENS, JJJ

1993-01-01

Girls with Turner syndrome were divided according to age (group A 6-12 years, and group B 12-19 years) and human growth hormone (GH) dose regimen (A1 and B1, three injections/week; A2 and B2, six injections/week). All groups responded to GH, 24 IU/M2/week, with an increase in height velocity, though

29 CFR 778.114 - Fixed salary for fluctuating hours.

Science.gov (United States)

2010-07-01

..., whatever their number, rather than for working 40 hours or some other fixed weekly work period, such a... compensation to the employee at a rate not less than the applicable minimum wage rate for every hour worked in..., in addition to such salary, for all overtime hours worked at a rate not less than one-half his...

A short 2 week dose titration regimen reduces the severity of flu-like symptoms with initial interferon gamma-1b treatment.

Science.gov (United States)

Devane, John G; Martin, Mary L; Matson, Mark A

2014-06-01

Flu-like symptoms (FLS) are commonly experienced by patients receiving interferon gamma-1b which may cause discontinuation or disruption of dosing during initial therapy or on re-initiation following a break in therapy. In contrast to Type I interferons, the impact of dose-titration on FLS has not been reported and is not a practice described or included in the approved prescribing information for interferon gamma-1b.The objective of this study was to assess the effect of a 2 week titration regimen on the severity of FLS during the initial 3 weeks of therapy with three times weekly subcutaneous injections of interferon gamma-1b. Healthy men and women were randomized into a double-blind, two-period, crossover study. Each study period was 3 weeks in duration and there was a minimum 15 day washout between treatment periods. Two treatment regimens were compared: No Titration dosing (full 50 mcg/m(2) subcutaneously [s.c.] three times weekly for 3 weeks) and Titration (15 mcg/m(2) s.c. three times weekly during week 1, 30 mcg/m(2) s.c. three times weekly during week 2 followed by the full dose of 50 mcg/m(2) s.c. three times weekly during week 3). Subjects remained in the clinic for at least 12 hours following each injection. FLS was based on a composite score for fever, chills, tiredness and muscle aches assessed at baseline and 4, 8 and 12 hours following each injection. Acetaminophen was allowed at the discretion of the PI. The primary endpoint was the change from baseline in FLS severity at 8 hours averaged over the 3 weeks of treatment. Additional endpoints included FLS at 4 and 12 hours, individual flu-like symptoms, rates of discontinuation, incidence of FLS and acetaminophen use. NCT 01929382. Of the 40 subjects randomized, there were 15 (37.5%) discontinuations. Titration resulted in a significant reduction in FLS severity at 8 hours (p = 0.023) averaged over the 3 week treatment period. The difference in 3 week FLS severity reflects differences

Extended high dose letrozole regimen versus short low dose letrozole regimen as an adjuvant to gonadotropin releasing hormone antagonist protocol in poor responders undergoing IVF-ET.

Science.gov (United States)

Fouda, Usama M; Sayed, Ahmed M

2011-12-01

To compare the efficacy and cost-effectiveness of extended high dose letrozole regimen/HPuFSH-gonadotropin releasing hormone antagonist (GnRHant) protocol with short low dose letrozole regimen/HPuFSH-GnRHant protocol in poor responders undergoing IVF-ET. In this randomized controlled trial, 136 women who responded poorly to GnRH agonist long protocol in their first IVF cycle were randomized into two equal groups using computer generated list and were treated in the second IVF cycle by either extended letrozole regimen (5 mg/day during the first 5 days of cycle and 2.5 mg/day during the subsequent 3 days) combined with HPuFSH-GnRHant protocol or short letrozole regimen (2.5 mg/day from cycle day 3-7) combined with HPuFSH-GnRHant protocol. There were no significant differences between both groups with regard to number of oocytes retrieved and clinical pregnancy rate (5.39 ± 2.08 vs. 5.20 ± 1.88 and 22.06% vs. 16.18%, respectively).The total gonadotropins dose and medications cost per cycle were significantly lower in extended letrozole group (44.87 ± 9.16 vs. 59.97 ± 14.91 ampoules and 616.52 ± 94.97 vs. 746.84 ± 149.21 US Dollars ($), respectively).The cost-effectiveness ratio was 2794 $ in extended letrozole group and 4616 $ in short letrozole group. Extended letrozole regimen/HPuFSH-GnRHant protocol was more cost-effective than short letrozole regimen/HPuFSH-GnRHant protocol in poor responders undergoing IVF-ET.

Dosimetric comparison between fixed and individualized activity in Graves' disease treatment with 131{sub I}; Comparacion dosimetrica entre actividad fiija y actividad individualizada en el tratamiento de la enfermedad de Graves con 131{sub I}

Energy Technology Data Exchange (ETDEWEB)

Melgar Perez, J.; Orellana Salas, A.; Santaella Guardiola, Y.; Arrocha Acevedo, J. F.

2013-07-01

A patient-especific method has been used to calculate the therapeutic {sup 1}'3{sup 1} I activity to administer to patients with Graves disease in order to obtain the optimal thyroid dose. The aim of this study was to analyze the dose variation in contrast to the fixed a ctivity regimen. In 30 patients, biokinetic and morfological parameters were estimated from planar scintigraphic images obtained at 4, 24 and 96 hours after injection of {sup 123} I and {sup 131} I activities were calculated to deliver 120 Gy to the thyroid. Comparative dose calculations were carried out assuming that the individual patients had been treated according to 370 MBq activity administration. Activity (or dose) was reduced by an average factor of 2.4 and up to a factor 4.9 for an individual patient. The implemen ted method seeks a balance among the accuracy of the calculations, resource consumption and patient comfort. (Author)

Escitalopram in obsessive-compulsive disorder: a randomized, placebo-controlled, paroxetine-referenced, fixed-dose, 24-week study

DEFF Research Database (Denmark)

Stein, Dan J; Andersen, Elisabeth Anne Wreford; Tonnoir, Brigitte

2007-01-01

OBJECTIVE: A randomized, placebo controlled fixed-dose trial was undertaken to determine the efficacy and tolerability of escitalopram in obsessive-compulsive disorder (OCD), using paroxetine as the active reference. RESEARCH DESIGN AND METHODS: A total of 466 adults with OCD from specialized...... clinical centres, psychiatric hospital departments, psychiatric practices, or general practice were randomized to one of four treatment groups: escitalopram 10 mg/day (n = 116), escitalopram 20 mg/day (n = 116), paroxetine 40 mg/day (n = 119), or placebo (n = 115) for 24 weeks. The primary efficacy...... of adverse events, and on changes in vital signs (blood pressure and pulse). Main outcome measures; RESULTS: Escitalopram 20 mg/day was superior to placebo on the primary and all secondary outcome endpoints, including remission. Escitalopram 10 mg/day and paroxetine 40 mg/day were also effective...

Hardness, function, emotional well-being, satisfaction and the overall sexual experience in men using 100-mg fixed-dose or flexible-dose sildenafil citrate.

Science.gov (United States)

Ströberg, P; Kaminetsky, J C; Park, N C; Goldfischer, E R; Creanga, D L; Stecher, V J

2010-01-01

The prescribing information for sildenafil citrate (VIAGRA, Pfizer, New York, NY, USA) recommends flexible dosing (50 mg initially, adjusted to 100 or 25 mg based on effectiveness and tolerability) in most men with erectile dysfunction (ED). In many men, however, 100 mg may be the most appropriate initial dose because it would reduce the need for titration and could prevent discouragement and treatment abandonment should 50 mg be insufficient. Results of two previously published double-blind, placebo-controlled sildenafil trials of similar design except for a fixed-dose vs flexible-dose regimen were analyzed. Relative to the flexible-dose, approximately one-third more men were satisfied with an initial and fixed dose of 100 mg. In addition, tolerability was similar, and improvements from baseline in outcomes on validated, ED-specific, patient-reported questionnaires were either similar (erectile function and the percentage of completely hard and fully rigid erections) or greater (emotional well-being and the overall sexual experience). The similarity in outcomes is not surprising given that almost 90% of the men in the flexible-dose trial titrated to 100 mg after 2 weeks. These data suggest prescription of an initial dose of 100 mg for men with ED, except in those for whom it is inappropriate.

Agreement between 24-hour salt ingestion and sodium excretion in a controlled environment.

Science.gov (United States)

Lerchl, Kathrin; Rakova, Natalia; Dahlmann, Anke; Rauh, Manfred; Goller, Ulrike; Basner, Mathias; Dinges, David F; Beck, Luis; Agureev, Alexander; Larina, Irina; Baranov, Victor; Morukov, Boris; Eckardt, Kai-Uwe; Vassilieva, Galina; Wabel, Peter; Vienken, Jörg; Kirsch, Karl; Johannes, Bernd; Krannich, Alexander; Luft, Friedrich C; Titze, Jens

2015-10-01

Accurately collected 24-hour urine collections are presumed to be valid for estimating salt intake in individuals. We performed 2 independent ultralong-term salt balance studies lasting 105 (4 men) and 205 (6 men) days in 10 men simulating a flight to Mars. We controlled dietary intake of all constituents for months at salt intakes of 12, 9, and 6 g/d and collected all urine. The subjects' daily menus consisted of 27 279 individual servings, of which 83.0% were completely consumed, 16.5% completely rejected, and 0.5% incompletely consumed. Urinary recovery of dietary salt was 92% of recorded intake, indicating long-term steady-state sodium balance in both studies. Even at fixed salt intake, 24-hour urine collection for sodium excretion (UNaV) showed infradian rhythmicity. We defined a ±25 mmol deviation from the average difference between recorded sodium intake and UNaV as the prediction interval to accurately classify a 3-g difference in salt intake. Because of the biological variability in UNaV, only every other daily urine sample correctly classified a 3-g difference in salt intake (49%). By increasing the observations to 3 consecutive 24-hour collections and sodium intakes, classification accuracy improved to 75%. Collecting seven 24-hour urines and sodium intake samples improved classification accuracy to 92%. We conclude that single 24-hour urine collections at intakes ranging from 6 to 12 g salt per day were not suitable to detect a 3-g difference in individual salt intake. Repeated measurements of 24-hour UNaV improve precision. This knowledge could be relevant to patient care and the conduct of intervention trials. © 2015 American Heart Association, Inc.

Population Pharmacokinetic Model for Vancomycin Used in Open Heart Surgery: Model-Based Evaluation of Standard Dosing Regimens.

Science.gov (United States)

Alqahtani, Saeed A; Alsultan, Abdullah S; Alqattan, Hussain M; Eldemerdash, Ahmed; Albacker, Turki B

2018-04-23

The purpose of this study was to investigate the population pharmacokinetics of vancomycin in patients undergoing open heart surgery. In this observational pharmacokinetic study, multiple blood samples were drawn over a 48-h period of intravenous vancomycin in patients who were undergoing open heart surgery. Blood samples were analysed using the Architect i4000SR Immunoassay Analyzer. Population pharmacokinetic models were developed using Monolix 4.4 software. Pharmacokinetic-pharmacodynamic (PK-PD) simulations were performed to explore the ability of different dosage regimens to achieve the pharmacodynamic targets. One-hundred and sixty-eight blood samples were analysed from 28 patients. The pharmacokinetics of vancomycin was best described by a two-compartment model with between-subject variability in CL, V of the central compartment, and V of the peripheral compartment. CL and central compartment V of vancomycin were related to CL CR , body weight, and albumin concentration. Dosing simulations showed that standard dosing regimens of 1 and 1.5 g failed to achieve the PK-PD target of AUC 0--24 /MIC > 400 for an MIC of 1 mg/L, while high weight-based dosing regimens were able to achieve the PK-PD target. In summary, administration of standard doses of 1 and 1.5 g of vancomycin two times daily provided inadequate antibiotic prophylaxis in patients undergoing open heart surgery. The same findings were obtained when 15 mg/kg and 20 mg/kg doses of vancomycin were administered. Achieving the PK-PD target required higher doses (25 mg/kg and 30 mg/kg) of vancomycin. Copyright © 2018 American Society for Microbiology.

Flexibility of working hours in the 24-hour society.

Science.gov (United States)

Costa, G

2006-01-01

The 24-hour Society undergoes an ineluctable process towards a social organisation where time constraints are no more restricting human life. The borders between working and social times are no more fixed and rigidly determined, and the value of working time changes according to the different economic and social effects you may consider. Shift and night work, irregular and flexible working hours, together with new technologies, are the milestone of this epochal passage. What are the advantages and disadvantages for the individual, the companies, and the society? What is the cost/benefit ratio in terms of health and social well-being? Coping properly with this process means avoiding a passive acceptance of it with consequent maladjustments at both individual and social level, but adopting effective preventive and compensative strategies aimed at building up a more sustainable society. Flexible working times now appear to be one of the best ways to cope with the demands of the modern life, but there are different points of view about labour and temporal 'flexibility" between employers and employees. For the former it means a prompt adaptation to market demands and technological innovations; for the latter it is a way to improve working and social life, by decreasing work constraints and increasing control and autonomy. Although it can be easily speculated that individual-based 'flexibility" should improve health and well-being, and especially satisfaction, whereas company-based flexibility" might interfere negatively, the effective consequences on health and well-being have still to be analysed properly.

Hardness, function, emotional well-being, satisfaction and the overall sexual experience in men using 100-mg fixed-dose or flexible-dose sildenafil citrate

Science.gov (United States)

Ströberg, P; Kaminetsky, J C; Park, N C; Goldfischer, E R; Creanga, D L; Stecher, V J

2010-01-01

The prescribing information for sildenafil citrate (VIAGRA, Pfizer, New York, NY, USA) recommends flexible dosing (50 mg initially, adjusted to 100 or 25 mg based on effectiveness and tolerability) in most men with erectile dysfunction (ED). In many men, however, 100 mg may be the most appropriate initial dose because it would reduce the need for titration and could prevent discouragement and treatment abandonment should 50 mg be insufficient. Results of two previously published double-blind, placebo-controlled sildenafil trials of similar design except for a fixed-dose vs flexible-dose regimen were analyzed. Relative to the flexible-dose, approximately one-third more men were satisfied with an initial and fixed dose of 100 mg. In addition, tolerability was similar, and improvements from baseline in outcomes on validated, ED-specific, patient-reported questionnaires were either similar (erectile function and the percentage of completely hard and fully rigid erections) or greater (emotional well-being and the overall sexual experience). The similarity in outcomes is not surprising given that almost 90% of the men in the flexible-dose trial titrated to 100 mg after 2 weeks. These data suggest prescription of an initial dose of 100 mg for men with ED, except in those for whom it is inappropriate. PMID:20596083

Bioequivalence of isoniazid in a two drug fixed dose combination and in a single drug dosage form.

Science.gov (United States)

Agrawal, S; Kaul, C L; Panchagnula, R

2001-08-01

To increase the patient compliance and reduce the risk of drug resistant strains, WHO and IUATLD recommend the use of Fixed Dose Combination (FDC) tablets as a routine therapeutic regimen in Directly Observed Treatment Shortcourse (DOTS). But the main issue in the use of FDC is the quality of the formulation. At present WHO and IUATLD suggest the bioequivalence assessment of only rifampicin from FDC compared to separate formulations. For the therapeutic effectiveness all the components of the FDCs should be bioavailable at tissue site. Also, the primary and acquired resistance rate of isoniazid is much higher compared to other anti-tubercular drugs. Hence, a comparative bioavailability study of isoniazid from a two drugs FDC compared to a separate formulation was carried out on a group of 12 healthy volunteers. When evaluated by normal or log transformed confidence interval, Two Way ANOVA and Hauschke analysis, the bioequivalence limits for AUC0-8 and AUC0-24 were within 0.8-1.25. For Cmax and Tmax, these limits were within 0.7-1.43. Hence, isoniazid from a FDC formulation was found to be bioequivalent to a separate formulation at same dose levels.

New dosing strategies for an old antibiotic: pharmacodynamics of front-loaded regimens of colistin at simulated pharmacokinetics in patients with kidney or liver disease.

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Rao, Gauri G; Ly, Neang S; Haas, Curtis E; Garonzik, Samira; Forrest, Alan; Bulitta, Jurgen B; Kelchlin, Pamela A; Holden, Patricia N; Nation, Roger L; Li, Jian; Tsuji, Brian T

2014-01-01

Increasing evidence suggests that colistin monotherapy is suboptimal at currently recommended doses. We hypothesized that front-loading provides an improved dosing strategy for polymyxin antibiotics to maximize killing and minimize total exposure. Here, we utilized an in vitro pharmacodynamic model to examine the impact of front-loaded colistin regimens against a high bacterial density (10(8) CFU/ml) of Pseudomonas aeruginosa. The pharmacokinetics were simulated for patients with hepatic (half-life [t1/2] of 3.2 h) or renal (t1/2 of 14.8 h) disease. Front-loaded regimens (n=5) demonstrated improvement in bacterial killing, with reduced overall free drug areas under the concentration-time curve (fAUC) compared to those with traditional dosing regimens (n=14) with various dosing frequencies (every 12 h [q12h] and q24h). In the renal failure simulations, front-loaded regimens at lower exposures (fAUC of 143 mg · h/liter) obtained killing activity similar to that of traditional regimens (fAUC of 268 mg · h/liter), with an ∼97% reduction in the area under the viable count curve over 48 h. In hepatic failure simulations, front-loaded regimens yielded rapid initial killing by up to 7 log10 within 2 h, but considerable regrowth occurred for both front-loaded and traditional regimens. No regimen eradicated the high bacterial inoculum of P. aeruginosa. The current study, which utilizes an in vitro pharmacodynamic infection model, demonstrates the potential benefits of front-loading strategies for polymyxins simulating differential pharmacokinetics in patients with hepatic and renal failure at a range of doses. Our findings may have important clinical implications, as front-loading polymyxins as a part of a combination regimen may be a viable strategy for aggressive treatment of high-bacterial-burden infections.

Quantitation of 24-Hour Moisturization by Electrical Measurements of Skin Hydration.

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Wickett, R Randall; Damjanovic, Bronson

The purpose of this study was to quantify the effects of several moisturizers on hydration of the stratum corneum by measuring their effect on electrical conductance over a 24-hour period. Double-blind, randomized controlled trial. Twenty-five healthy female volunteers aged 18 to 65 years with dry skin on the lower legs and no other known dermatologic pathology participated in the study. Additional exclusion criteria were pregnant or taking anti-inflammatory steroids. The study was carried out in a clinical research facility in Winnipeg, Manitoba, Canada. Subjects underwent a 3-day conditioning period using a natural soap bar on the lower legs and no application of moisturizer to the skin. Participants then came to the test site and equilibrated for at least 30 minutes under controlled conditions of temperature and humidity. After baseline hydration measurements on test sites on the lower legs of each subject, a single application of each of 5 test products at a dose of 2 mg/cm was made. Skin hydration was assessed by electrical conductance measurements with a specialized probe. The probe was briefly placed on the skin surface with light pressure, and the measurement recorded in units of microsiemens (μS). Conductance was measured at 2, 4, 6, 8, and 24 hours after product applications. Although all but 1 of the test products increased conductance at 2 hours, only 2 moisturizers containing high levels of glycerin (products C and E) maintained increased conductance relative to baseline at 24 hours, +37.8 (P skin conductance for at least 24 hours after a single application.

Evaluation of radioiodine therapy with fixed doses of 10 and 15 mCi in patients with Graves disease; Avaliacao da radioiodoterapia com doses fixas de 10 e 15 mCi em pacientes com doenca de Graves

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Canadas, Viviane; Vilar, Lucio; Moura, Eliane; Brito, Ana; Castellar, Enio [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Hospital das Clinicas. Servico de Endocrinologia]. E-mail: vivi2207@ig.com.br

2007-10-15

The treatment options for the hyperthyroidism of Graves' disease are antithyroid drugs, surgery and radioiodine, none of which is considered ideal, as they do not act directly on the etiopathogenesis of the disease. Radioiodine has been increasingly used as the treatment of choice because it is a safe and definitive therapy whose administration is very easy. Some authors prefer to administer higher doses in order to deliberately induce hypothyroidism, while others recommend lower doses that result in a lower incidence of hypothyroidism and a greater incidence of euthyroidism. There is no consensus for the optimal regimen of fixed doses to be used and this is the main focus of the present study, where doses of 10 and 15 mCi of {sup 131}I were compared. Among the 164 patients analyzed, 61 (37.2%) were submitted to 10 mCi and 103 (62.8%) to 15 mCi. In the longitudinal analysis it was observed that remission of the hyperthyroidism was statistically different in the sixth month (p < 0.001), being higher in the group that used the dose of 15 mCi, but similar in both groups at 12 and 24 months. It may be concluded that the administration of fixed doses of 10 and 15 mCi of {sup 131}I brought about a similar remission of the hyperthyroidism after 12 months of treatment. Moreover, the remission rate of the hyperthyroidism had no association with age, sex or previous therapy with antithyroid drugs. (author)

24-Hour Academic Libraries: Adjusting to Change

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Bowman, Adam C.

2013-01-01

The purpose of this study was to explore the adaptive measures that academic libraries perform when implementing and operating a 24-hour schedule. Five in-depth interviews were conducted with current managerial-level librarians at 24-hour academic libraries. The exploratory interviews revealed similar measures for security, budgeting, employee…

Treatment Compliance with Fixed-Dose Combination of Vildagliptin/Metformin in Patients with Type 2 Diabetes Mellitus Inadequately Controlled with Metformin Monotherapy: A 24-Week Observational Study

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Grigorios Rombopoulos

2015-01-01

Full Text Available Objective. To evaluate the differences in treatment compliance with vildagliptin/metformin fixed-dose versus free-dose combination therapy in patients with type 2 diabetes mellitus (T2DM in Greece. Design. Adult patients with T2DM, inadequately controlled with metformin monotherapy, (850 mg bid, participated in this 24-week, multicenter, observational study. Patients were enrolled in two cohorts: vildagliptin/metformin fixed-dose combination (group A and vildagliptin metformin free-dose combination (group B. Results. 659 patients were enrolled, 360 were male, with mean BMI 30.1, mean T2DM duration 59.6 months, and mean HbA1c at baseline 8%; 366 patients were assigned to group A and 293 to group B; data for 3 patients was missing. In group A, 98.9% of patients were compliant with their treatment compared to 84.6% of group B. The odds ratio for compliance in group A versus B was (OR 18.9 (95% CI: 6.2, 57.7; P<0.001. In group A mean HbA1c decreased from 8.1% at baseline to 6.9% (P<0.001 at the study end and from 7.9% to 6.8% (P<0.001 in group B. Conclusions. Patients in group A were more compliant than patients in group B. These results are in accordance with international literature suggesting that fixed-dose combination therapies lead to increased compliance to treatment.

Effects of telmisartan on office and 24-hour ambulatory blood pressure: an observational study in hypertensive patients managed in primary care

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Frederic Kontny

2010-01-01

Full Text Available Frederic Kontny1, Terje Risanger2, Arne Bye3, Øyvind Arnesen4, Odd Erik Johansen4 for the TELMIMORE Study Investigators51Dept of Cardiology, Volvat Medical Centre, Oslo, Norway; 2Prinsdal Health Centre, Oslo, Norway; 3Frosta Health Centre, Frosta, Norway; 4Medical Department, Boehringer-Ingelheim Norway KS, Asker, Norway; 5The TELMIMORE Study Investigators are listed at the end of the paperPurpose: Although elevated blood pressure (BP predicts future cardiovascular events, recommended BP targets often is not reached in the general community. In a clinical real-life setting we evaluated BP impact and tolerability of the angiotensin-II receptor blocker telmisartan in patients with essential hypertension.Patients and methods: Patients in this observational study not at target BP started or switched to telmisartan monotherapy (40 or 80 mg or a fixed-dose combination of telmisartan and hydrochlorothiazide (HCT 80 mg/12.5 mg. Office and 24-hour ambulatory BP (AMBP were measured before and after 8 weeks of treatment and physicians reported perceived drug efficacy and tolerability as “Very good”, “Good”, “Moderate” or “Bad”.Results: 100 patients (34% female, 60 years, BMI 29.4 kg/m2, mean office BP 159/92 mmHg of whom 38% were treatment naïve and 30%, 17%, 9% and 6% respectively were on 1, 2, 3 or 4 BP-lowering drugs, completed 8 weeks of treatment. The proportion of patients with office BP < 140/90 mmHg increased from 3% to 54% for systolic (P < 0.001, 38% to 75% for diastolic (P < 0.001, and 2% to 45% for systolic and diastolic BP (P < 0.001. A significant effect on BP levels was seen in patients being either treatment naïve or on 1 to 3 BP-lowering drugs at study entry, whereas no BP improvement occurred in those who switched from 4 drugs. Overall, mean 24-hour AMBP was reduced from 141/85 to 131/79 mmHg (P < 0.001. Drug efficacy and tolerability were perceived as “Very good” or “Good” by 44%/34% and 66%/27%, respectively

CLINICAL AND PHARMACOLOGICAL APPROACHES TO OPTIMIZE THE DOSING REGIMEN OF ANTIBACTERIAL DRUGS IN PEDIATRICS

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Natal’ya B. Lazareva

2018-01-01

Full Text Available The rational use of antibacterial drugs in children implies an adequate choice of the necessary medication, its dosing regimen, and the duration of treatment in order to achieve maximum efficacy and minimize toxic effects. The knowledge of pharmacokinetic and pharmacodynamic profiles of the antibacterial drug plays a crucial role for optimizing the dosing regimen. The strategy of individual choice of the dosing regimen, taking into account the principles of pharmacokinetics and pharmacodynamics, can be especially effective in patients with the expectedly changed parameters of pharmacokinetics and in infections caused by bacteria strains with low sensitivity to antibiotics. The review presents a contemporary view of pharmacokinetic and pharmacodynamic profiles of antibacterial drugs most commonly used in pediatrics and their relationship to the clinical efficacy of the administered therapy.

A randomized controlled trial of increased dose and frequency of albendazole with standard dose DEC for treatment of Wuchereria bancrofti microfilaremics in Odisha, India.

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Kar, Shantanu Kumar; Dwibedi, Bhagirathi; Kerketa, Anna Salomi; Maharana, Antaryami; Panda, Sudanshu S; Mohanty, Prafulla Chandra; Horton, John; Ramachandran, Cherubala P

2015-03-01

Although current programmes to eliminate lymphatic filariasis have made significant progress it may be necessary to use different approaches to achieve the global goal, especially where compliance has been poor and 'hot spots' of continued infection exist. In the absence of alternative drugs, the use of higher or more frequent dosing with the existing drugs needs to be explored. We examined the effect of higher and/or more frequent dosing with albendazole with a fixed 300 mg dose of diethylcarbamazine in a Wuchereria bancrofti endemic area in Odisha, India. Following screening, 104 consenting adults were randomly assigned to treatment with the standard regimen annually for 24 months (S1), or annually with increased dose (800 mg albendazole)(H1) or with increased frequency (6 monthly) with either standard (S2) or increased (H2) dose. Pre-treatment microfilaria counts (GM) ranged from 348 to 459 mf/ml. Subjects were followed using microfilaria counts, OG4C3 antigen levels and ultrasound scanning for adult worm nests. Microfilarial counts tended to decrease more rapidly with higher or more frequent dosing at all time points. At 12 months, Mf clearance was marginally greater with the high dose regimens, while by 24 months, there was a trend to higher Mf clearance in the arm with increased frequency and 800 mg of albendazole (76.9%) compared to other arms, (S1:64%, S2:69.2% & H1:73.1%). Although higher and/or more frequent dosing showed a trend towards a greater decline in antigenemia and clearance of "nests", all regimens demonstrated the potential macrofilaricidal effect of the combination. The higher doses of albendazole did not result in a greater number or more severe side effects. The alternative regimens could be useful in the later stages of existing elimination programmes or achieving elimination more rapidly in areas where programmes have yet to start.

Efficacy and Tolerability of Fixed-Dose Combination of Dexketoprofen and Dicyclomine Injection in Acute Renal Colic

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A. Porwal

2012-01-01

Full Text Available Objective. To evaluate the efficacy and tolerability of a fixed-dose combination of dexketoprofen and dicyclomine (DXD injection in patients with acute renal colic. Patients and Methods. Two hundred and seventeen patients were randomized to receive either DXD (n=109 or fixed-dose combination of diclofenac and dicyclomine injection (DLD; n=108, intramuscularly. Pain intensity (PI was self-evaluated by patients on visual analogue scale (VAS at baseline and at 1, 2, 4, 6, and 8 hours. Efficacy parameters were proportion of responders, difference in PI (PID at 8 hours, and sum of analogue of pain intensity differences (SAPID. Tolerability was assessed by patients and physicians. Results. DXD showed superior efficacy in terms of proportion of responders (98.17% versus 81.48; P<0.0001, PID at 8 hours (P=0.002, and SAPID0–8 hours (P=0.004. The clinical global impression for change in pain was significantly better for DXD than DLD. The incidence of adverse events was comparable in both groups. However, global assessment of tolerability was rated significantly better for DXD. Conclusion. DXD showed superior efficacy and tolerability than DLD in patients clinically diagnosed to be suffering from acute renal colic.

Efficacy and Tolerability of Fixed-Dose Combination of Dexketoprofen and Dicyclomine Injection in Acute Renal Colic

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Porwal, A.; Mahajan, A. D.; Oswal, D. S.; Erram, S. S.; Sheth, D. N.; Balamurugan, S.; Kamat, V.; Enadle, R. P.; Badadare, A.; Bhatnagar, S. K.; Walvekar, R. S.; Dhorepatil, S.; Naik, R. C.; Basu, I.; Kshirsagar, S. N.; Keny, J. V.; Sengupta, S.

2012-01-01

Objective. To evaluate the efficacy and tolerability of a fixed-dose combination of dexketoprofen and dicyclomine (DXD) injection in patients with acute renal colic. Patients and Methods. Two hundred and seventeen patients were randomized to receive either DXD (n = 109) or fixed-dose combination of diclofenac and dicyclomine injection (DLD; n = 108), intramuscularly. Pain intensity (PI) was self-evaluated by patients on visual analogue scale (VAS) at baseline and at 1, 2, 4, 6, and 8 hours. Efficacy parameters were proportion of responders, difference in PI (PID) at 8 hours, and sum of analogue of pain intensity differences (SAPID). Tolerability was assessed by patients and physicians. Results. DXD showed superior efficacy in terms of proportion of responders (98.17% versus 81.48; P < 0.0001), PID at 8 hours (P = 0.002), and SAPID0–8 hours (P = 0.004). The clinical global impression for change in pain was significantly better for DXD than DLD. The incidence of adverse events was comparable in both groups. However, global assessment of tolerability was rated significantly better for DXD. Conclusion. DXD showed superior efficacy and tolerability than DLD in patients clinically diagnosed to be suffering from acute renal colic. PMID:22577544

Fixed-dose lercanidipine/enalapril for hypertension.

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Menne, Jan; Haller, Hermann

2008-04-01

The dihydropyridine calcium channel blocker lercanidipine and the ACE inhibitor enalapril are frequently used in the treatment of hypertensive patients. In April 2007, a fixed-dose combination of the two drugs was approved in Germany for the treatment of patients not responding to monotherapy. It is expected that the drug will soon be available in the other European Union markets. In this review the present literature is summarized. Two doses will be available with 10 mg lercanidipine each and 10 or 20 mg enalapril. The medication should be taken once daily, optimally =15 minutes before a meal and the consumption of grapefruit juice should be avoided. The fixed-dose combination of the two drugs has a stronger blood pressure-lowering effect than monotherapy with 20 mg enalapril or 10 mg lercanidipine. The combination is well tolerated and few patients stopped the treatment because of side effects. As expected, the most common side effects reported are cough, peripheral edema, flushing, dizziness and vertigo, occurring in 1-5% of patients. This new fixed-dose combination is a useful adjunct to the present treatment and should increase compliance and help reduce hypertension-related costs. 2008 Prous Science, S.A.U. or its licensors

Correlations of post-implant regional dosimetric parameters at 24 hours and one month, with clinical results of low-dose-rate brachytherapy for localized prostate cancer

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Eiichiro Okazaki

2017-12-01

Full Text Available Purpose : To evaluate the correlations of post-implant regional dosimetrics at 24 hours (24 h and 1 month after implant procedures, with clinical outcomes of low-dose-rate (LDR brachytherapy for localized prostate cancer. Material and methods : Between January 2008 and December 2014, 130 consecutive patients treated for localized prostate cancer, receiving definitive iodine-125 ( 125 I brachytherapy treatment were retrospectively analyzed. All patients underwent post-implant CT imaging for dosimetric analysis at 24 h and 1 month after implantation procedure. Prostate contours were divided into quadrants: anterior-superior (ASQ, posterior-superior (PSQ, anterior-inferior (AIQ, and posterior-inferior (PIQ. Predictive factors and cut-off values of biochemical failure-free survival (BFFS and toxicities of LDR brachytherapy were analyzed. Results : The median follow-up time was 69.5 months. Seven patients (5.4% had biochemical failure. The 3-year and 5-year BFFS rates were 96.7% and 93.1%, respectively. On multivariate analysis, prostate-specific antigen and Gleason score were significant prognostic factors for biochemical failure. D 90 (the minimal dose received by 90% of the volume of PSQ and PIQ at 24 h, and D 90 of PSQ at 1 month were also significant factors. The cut-off values of PSQ D 90 were 145 Gy at 24 h and 160 Gy at 1 month. D 90 of the whole prostate was not significant at 24 h and at 1 month. D 90 of PSQ at 1 month was a significant factor for rectal hemorrhage. Conclusions : Post-implant D 90 of PSQ is significantly associated with BFFS for localized prostate cancer not only at 1 month, but also at 24 hours. D 90 of PSQ at 1 month is also a significant factor for rectal hemorrhage.

Comparison of Fixed versus Calculated Activity of Radioiodine for the Treatment of Graves Disease in Adults

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Abigail U. Canto

2016-03-01

Full Text Available BackgroundRadioactive iodine as a treatment modality has been shown in several studies to be a safe and effective therapy for Graves disease. However, there is still no uniformity regarding optimal dosing method. The aim of this study is to compare the efficacy of calculated and fixed dosing of radioiodine for the treatment of Graves disease.MethodsA hundred twenty-two patients diagnosed with Graves disease were randomized to receive either fixed or calculated dose of radioiodine. Those randomized to fixed activity received either low fixed activity at 9.9 mCi for thyroid gland size <40 g or high fixed activity at 14.9 mCi for thyroid gland size 40 to 80 g, and those grouped to calculated activity received 160 µCi/g of thyroid tissue adjusted for 24 hours radioiodine uptake. Thyroid function tests (free thyroxine [T4] and thyroid stimulating hormone [TSH] were monitored at 10, 16, and 24 weeks after radioactive iodine therapy. The primary outcome, treatment failure was defined as persistently elevated free T4 and low TSH.ResultsOf the 122 patients randomized, 56 in the fixed dose group and 56 in the calculated dose group completed the follow-up. At the end of 6 months, the percentage of treatment failure was 37.50% in the calculated dose group versus 19.64% in the fixed dose group with a relative risk of 0.53 (95% confidence interval, 0.28 to 0.98 favoring the fixed dose group.ConclusionFixed dose radioiodine has a significantly lower incidence of persistent hyperthyroidism at 6 months post-radioactive therapy.

Fixed dose darunavir boosted with cobicistat combined with emtricitabine and tenofovir alafenamide fumarate.

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Cevik, Muge; Orkin, Chloe

2018-07-01

In an era when virological efficacy approaches 100%, novel antiretroviral (ARV) therapies must deliver better tolerability, safety, and convenient coformulated regimens. We review the phase II and III clinical data on the fixed dose combination (FDC) darunavir (DRV) 800mg / cobicistat (COBI/C) 150 mg / emtricitabine (F/FTC) 200 mg / tenofovir alafenamide fumarate (TAF) 10mg (D/C/F/TAF) for the treatment of HIV-1 infection. In an exploratory phase II study, D/C/F/TAF FDC demonstrated similar virological efficacy to darunavir/cobicistat FDC + F /tenofovir disoproxil fumarate (TDF) FDC in treatment-naive HIV-1-infected individuals with favorable bone and renal outcomes. These findings led to two subsequent international phase III double-blind randomized controlled trials; AMBER and EMERALD. In the (treatment naïve) AMBER study, D/C/F/TAF FDC was noninferior to component regimen F/TDF + darunavir/cobicistat with favorable bone and renal outcomes at week 48. In the EMERALD study (switch study for virologically suppressed patients), D/C/F/TAF showed noninferior efficacy to F/TDF and boosted protease inhibitor (bPI) regimen at week 48 also with favorable renal and bone outcomes. No virological failure was observed, and no resistance to TDF or darunavir emerged in either study. In clinical trials, D/C/F/TAF FDC demonstrated excellent, noninferior virological efficacy, maintained a high genetic barrier and conferred the additional safety benefits of TAF. As the first one pill, once daily, protease inhibitor-based regimen, D/C/F/TAF FDC offers a new option for the treatment of HIV infection.

Geneva 24 hours swim

CERN Document Server

2003-01-01

The 18th edition of the Geneva 24 hours swim competition will take place at the Vernets Swimming Pool on the 4th and 5th of October. More information and the results of previous years are given at: http://www.carouge-natation.com/24_heures/home_24_heures.htm Last year, CERN obtained first position in the inter-company category with a total of 152.3 kms swam by 45 participants. We are counting on your support to repeat this excellent performance this year. For those who would like to train, the Livron swimming pool in Meyrin is open as from Monday the 8th September. For further information please do not hesitate to contact us. Gino de Bilio and Catherine Delamare

Geneva 24 Hours Swim

CERN Document Server

2003-01-01

The 18th edition of the Geneva 24 hours swim competition will take place at the Vernets Swimming Pool on the 4th and 5th of October. More information and the results of previous years are given at: http://www.carouge-natation.com/24_heures/home_24_heures.htm Last year, CERN obtained first position in the inter-company category with a total of 152.3 kms swam by 45 participants. We are counting on your support to repeat this excellent performance this year. For those who would like to train, the Livron swimming pool in Meyrin is open as from Monday the 8th September. For further information please do not hesitate to contact us. Gino de Bilio and Catherine Delamare

29 CFR 785.21 - Less than 24-hour duty.

Science.gov (United States)

2010-07-01

... Sleeping Time and Certain Other Activities § 785.21 Less than 24-hour duty. An employee who is required to be on duty for less than 24 hours is working even though he is permitted to sleep or engage in other... 29 Labor 3 2010-07-01 2010-07-01 false Less than 24-hour duty. 785.21 Section 785.21 Labor...

Efficacy and safety of two ramipril and hydrochlorothiazide fixed-dose combination formulations in adults with stage 1 or stage 2 arterial hypertension evaluated by using ABPM.

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Oigman, Wille; Gomes, Marco Antônio Mota; Pereira-Barretto, Antônio Carlos; Póvoa, Rui; Kohlmann, Osvaldo; Rocha, João Carlos; Nobre, Fernando

2013-05-01

Fixed-dose combinations of antihypertensive agents demonstrate advantages in terms of efficacy, tolerability, and treatment adherence. This study was designed to compare the efficacy and safety of 2 ramipril and hydrochlorothiazide (HCTZ) fixed-dose combinations in patients with hypertension stage 1 or 2. Patients' blood pressure (BP) profiles were evaluated by using 24-hour ambulatory BP monitoring (ABPM). This was a multicenter, prospective, randomized, open-label, parallel-group, noninferiority trial of adult patients (age ≥18 years) with hypertension stage 1 or 2 and systolic blood pressure (SBP) within 140 to 179 mm Hg or diastolic blood pressure (DBP) 90 to 109 mm Hg. After a 2-week washout period, eligible patients were randomized to receive 1 of 2 ramipril/HCTZ fixed-dose combination formulations (5/25 mg/d) for 8 weeks. The primary end point was the difference in 24-hour ABPM SBP/DBP mean reductions between groups after 8 weeks of treatment. The secondary end points were the changes in daytime and nighttime ABPM and in office BP. Safety profile and tolerability assessments included monitoring of adverse events. A total of 102 patients with hypertension (54 in group A [test formulation] and 48 in group B [reference formulation]), aged 27 to 85 years, completed the 8-week treatment period. The decreases in SBP and DBP according to 24-hour ABPM from baseline to week 8 were significant and similar in both groups. SBP decreased from 149.1 to 133.0 mm Hg (-16.1 mm Hg) in group A and from 146.2 to 130.6 mm Hg in group B (-15.6 mm Hg) (P = 0.8537); DBP was reduced by 8.8 mm Hg in group A and by 8.5 mm Hg in group B (P = 0.8748). Because the lower 95% CI limit for the difference between groups A and B of 3.96 mm Hg in SBP and 3.54 mm Hg in DBP was lower than that preestablished by the trial protocol (4 mm Hg), noninferiority of the test formulation was demonstrated compared with the reference formulation. For the secondary end points, there was no significant

Clinical experience with fixed bimonthly aflibercept dosing in treatment-experienced patients with neovascular age-related macular degeneration

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Khanani AM

2015-07-01

Full Text Available Arshad M Khanani Sierra Eye Associates, Reno, NV, USA Purpose: To evaluate the durability of fixed bimonthly dosing of intravitreal aflibercept for neovascular age-related macular degeneration.Methods: Records of 16 patients were retrospectively reviewed. Patients received three initial 2.0 mg monthly doses of aflibercept then 8-weekly doses according to the product label. Best-corrected visual acuity (Early Treatment Diabetic Retinopathy Study [ETDRS] letters, central macular thickness, fluid on optical coherence tomography, and pigment epithelial detachment (PED were measured.Results: Prior to starting aflibercept, 13 patients had subretinal fluid (SRF, five had intraretinal fluid (IRF, four had PED, and baseline visual acuity (VA was 62 approximate ETDRS letters. Following the monthly dosing, seven patients had no improvement or decreased VA, ten patients still had SRF/IRF, and PED had worsened in one patient. At Visit 4, an average of 6.8 weeks after Visit 3, VA had decreased in seven patients, SRF/IRF had increased in 12 patients, and PED had returned in all patients who initially responded. Based on the presence of fluid after the initial monthly injections, 12 patients could not be extended to fixed bimonthly dosing.Conclusion: This case series adds to the growing body of evidence on the need for flexible dosing schedules for the personalized treatment of neovascular age-related macular degeneration. Keywords: age-related macular degeneration, AMD, bimonthly, regimen, aflibercept, case studies, retinal fluid

Multiple-dose pharmacokinetic study of proguanil and cycloguanil following 12-hourly administration of 100 mg proguanil hydrochloride.

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Jamaludin, A; Mohamad, M; Navaratnam, V; Yeoh, P Y; Wernsdorfer, W H

1990-09-01

A pharmacokinetic study with 12-hourly doses of 100 mg proguanil hydrochloride over 15 days has been conducted in six adult male Malaysian volunteers. Steady state for proguanil was established after the fourth dose on Day 2, for the active metabolite cycloguanil as from Day 3 inclusive. The steady state mean peak concentration of proguanil was 1201.6 +/- 132.4 nmol/l, the mean trough concentration 650.0 +/- 58.1 nmol/l. The corresponding values for cycloguanil were 317.0 +/- 44.4 nmol/l (mean peak) and 230.8 +/- 35.1 nmol/l (mean trough). The profiles and peak/trough ratios of proguanil and cycloguanil with 12-hourly dosing offer better prospects for protection against malaria than those obtained with 24-hourly doses of 200 mg proguanil hydrochloride, the current routine in malaria chemoprophylaxis.

Comparison of current recommended regimens of atropinization in organophosphate poisoning.

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Connors, Nicholas J; Harnett, Zachary H; Hoffman, Robert S

2014-06-01

Atropine is the mainstay of therapy in organophosphate (OP) toxicity, though research and consensus on dosing is lacking. In 2004, as reported by Eddleston et al. (J Toxicol Clin Toxicol 42(6):865-75, 2004), they noted variation in recommended regimens. We assessed revisions of original references, additional citations, and electronic sources to determine the current variability in atropine dosing recommendations. Updated editions of references from Eddleston et al.'s work, texts of Internal and Emergency Medicine, and electronic resources were reviewed for atropine dosing recommendations. For comparison, recommendations were assessed using the same mean dose (23.4 mg) and the highest dose (75 mg) of atropine as used in the original paper. Recommendations were also compared with the dosing regimen from the World Health Organization (WHO). Thirteen of the original recommendations were updated and 15 additional references were added giving a convenience sample of 28. Sufficient information to calculate time to targeted dose was provided by 24 of these samples. Compared to 2004, current recommendations have greatly increased the speed of atropinization with 13/24 able to reach the mean and high atropine dose within 30 min compared to 1/36 in 2004. In 2004, there were 13 regimens where the maximum time to reach 75 mg was over 18 h, whereas now, there are 2. While only one recommendation called for doubling the dose for faster escalation in 2004, 15 of the 24 current works include dose doubling. In 2004, Eddleston et al. called for an evidence-based guideline for the treatment of OP poisoning that could be disseminated worldwide. Many current recommendations can adequately treat patients within 1 h. While the WHO recommendations remain slow to treat patients with OP poisoning, other authorities are close to a consensus on rapid atropinization.

Bioequivalence of a fixed-dose repaglinide/metformin combination tablet and equivalent doses of repaglinide and metformin tablets
.

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Cho, Hea-Young; Ngo, Lien; Kim, Sang-Ki; Choi, Yoonho; Lee, Yong-Bok

2018-06-01

This study was conducted to determine whether a fixed-dose combination (FDC) tablet of repaglinide/metformin (2/500 mg) is equivalent to coadministration of equivalent doses of individual (EDI) tablets of repaglinide (2 mg) and metformin (500 mg) in healthy Korean male subjects. This study was conducted as an open-label, randomized, single-dose, two-period, two-sequence crossover design in 50 healthy Korean male subjects who received an FDC tablet or EDI tablets. Plasma concentrations of repaglinide and metformin were determined for up to 24 hours using a validated UPLC-MS/MS method. Bioequivalence was assessed according to current guidelines issued by the U.S. Food and Drug Administration (FDA) and Korean legislation. Tolerability was also evaluated throughout the study via subject interview, vital signs, and blood sampling. Point estimates (90% CIs) for AUC0-t, AUC0-∞, and Cmax based on EDI tablets were 110.07 (102.25 - 118.49), 109.90 (101.70 - 118.39), and 112.60 (101.49 - 124.85), respectively, for repaglinide. They were 95.18 (89.62 - 101.05), 95.00 (89.74 - 100.65), and 98.44 (92.72 - 104.50), respectively, for metformin. These results satisfied the bioequivalence criteria of 80.00 - 125.00% proposed by the FDA and Korean legislation. Results of pharmacokinetic analysis suggested that repaglinide and metformin in FDC tablets were bioequivalent to EDI tablets of repaglinide (2 mg) and metformin (500 mg) in healthy Korean male subjects. Both formulations appeared to be well tolerated.
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Studies on the T sub 3 suppression test with reference to the thyrodial sup 123 I uptake in Graves' disease; Comparison of 24-hour and 3-hour uptake

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Yamaguchi, Takahiko; Kobayashi, Isao; Yamaguchi, Yoshiyuki; Iwashita, Akira; Inukai, Toshihiko; Ohshima, Kihachi; Shimomura, Yohnosuke; Kobayashi, Setsuo (Gunma Univ., Maebashi (Japan). School of Medicine)

1990-06-01

Eighty-three patients with Graves' disease had been treated with methylmercaptoimidazole (MMI). They were prescribed a maintenance dose of antithyroid drug (MMI, 5 mg/day) at the time of a T{sub 3} suppression test. The 3-hour and 24-hour thyroidal {sup 123}I uptake after T{sub 3} administration (75 {mu}g/day, 2 weeks) were measured (post T{sub 3} uptake). In 38 patients whose post T{sub 3} uptake was below 35% in post T{sub 3} 24-hour uptake, treatment was stopped. The T{sub 3} suppression test was then repeated 1 and 3 months later. During a one-year follow up, 26 remained well, while 12 relapsed within 6 to 12 months. We have observed a good correlation between 3-hour uptake and 24-hour uptake of {sup 123}I after T{sub 3} administration (r=0.847, p<0.001). In 38 patients who showed positive T{sub 3} suppression, most patients with MMI withdrawal produced a marked overshoot of post T{sub 3} 3-hour and 24-hour uptake at one month. Retrospective analysis indicated that there was no significant difference in circulating thyroid hormone levels between remission and relapse groups. The present study provides evidence that 3-hour uptake values are able to be substituted for 24-hour uptake values during a T{sub 3} suppression test. In addition, overshoot of thyroidal uptake after antithyroid drug withdrawal was observed in 3-hour values, similar to 24-hour values. (author).

CORRELATION OF SPOT URINE ALBUMIN AND 12-HOUR URINE PROTEIN WITH 24-HOUR URINE PROTEIN IN PRE-ECLAMPSIA

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S. Vinayachandran

2017-11-01

Full Text Available BACKGROUND Pre-eclampsia is defined as the development of new-onset hypertension in the second half of pregnancy often accompanied by new-onset proteinuria with other signs and symptoms. Proteinuria is defined by the excretion of 300 mg or more of protein in a 24-hour urine collection. To avoid time consumed in collection of 24-hour urine specimens, efforts have been made to develop faster methods to determine concentration of urine protein. Preliminary studies have suggested that 12-hour urine protein collection maybe adequate for evaluation of pre-eclampsia with advantage of early diagnosis and treatment of pre-eclampsia as well as potential for early hospital discharge and increased compliance with specimen collection. The aim of the study is to evaluate and correlate spot urine albumin and 12-hour urine protein with 24-hour urine protein in pre-eclampsia. MATERIALS AND METHODS A diagnostic evaluation study- a 24-hour urine protein, 12-hour urine protein and spot urine albumin results are analysed. Correlation of 12-hour urine protein and spot urine albumin with 24-hour urine protein is analysed using SPSS software. The strength of correlation was measured by Pearson’s correlation coefficient (r. Student’s t-test and Chi-square tests were used to compare patients with and without 24-hour urine protein ≥300 mg. Probability value of 165 mg with 24-hour urine protein ≥300 mg suggest that this test has role in the evaluation of women with suspected pre-eclampsia and could be substituted for 24-hour urine protein as a simple, faster and cheaper method.

Efficacy of two regimens of dexamethasone for management of preterm labour: pilot study

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Rasool, A.; Farooq, U.

2017-01-01

Background: Dexamethasone is widely used for prevention of respiratory distress syndrome (RDS), necrotising enterocolitis (NEC) and intra-ventricular haemorrhage (IVH) in preterm babies; decreasing the neonatal mortality rate. There is no consensus on the dose of corticosteroid administered to the mother expected to have a preterm baby. This study is conducted to compare the effectiveness of two popular regimens of dexamethasone administration in decreasing incidence of RDS, necrotizing enterocolitis, IVH and neonatal mortality rate. Methods: Randomized control trial was conducted at Ayub Teaching Hospital, Abbottabad from 1st to 31st August, 2014. Sample size was set at 50. Block randomization was employed in the trial to allocate the patients into corresponding groups 'A' and 'B'. Group A was administered 6mg dexamethasone in 4 doses 12 hours apart and group B was administered 2 doses 12 hours apart. Results: Forty-eight patients participated in the study with 24 patients in each group. Mean age and period gestation of participants were 28.4 years±4.3 SD and 34 weeks±1.9 SD respectively. Four patients in group A gave birth to neonate with RDS compared to two cases in group B. Group B had higher incidence of necrotizing enterocolitis and neonatal mortalities. However, none of these differences observed were statistically significant. No case of IVH was reported in either of the groups. Conclusion: Both the popular regimens of dexamethasone administration are equally effective in decreasing the incidence of neonatal diseases. (author)

Excel VBA 24-hour trainer

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Urtis, Tom

2015-01-01

Master VBA automation quickly and easily to get more out of Excel Excel VBA 24-Hour Trainer, 2nd Edition is the quick-start guide to getting more out of Excel, using Visual Basic for Applications. This unique book/video package has been updated with fifteen new advanced video lessons, providing a total of eleven hours of video training and 45 total lessons to teach you the basics and beyond. This self-paced tutorial explains Excel VBA from the ground up, demonstrating with each advancing lesson how you can increase your productivity. Clear, concise, step-by-step instructions are combined wit

Heart Rate Variability in Obstetricians Working 14-Hour Call Compared to 24-Hour Call in Labour and Delivery.

Science.gov (United States)

Thurman, Robin H; Yoon, Eugene; Murphy, Kellie E; Windrim, Rory; Farrugia, M Michéle

2017-12-01

Obstetricians have stressful and demanding jobs that may impact their health. A physiological measurement of cardiac function which varies with stress is heart rate variability (HRV). By measuring the cyclic variations in R-R intervals, or beat-to-beat differences, HRV reflects the continuous interplay of the controlling forces in the autonomic nervous system. Studies have shown HRV to be reduced during periods of work-induced stress, including 24-hour shifts. Our study aimed to determine if there was a correlation between length of shift worked and HRV. We hypothesised that working for a full 24-hour period is more stressful than a shorter, nighttime-only period, and HRV analyses were used to measure this objectively. Obstetricians wore an HRV monitor for 24 hours during both a regular day followed by a 14-hour night shift and a continuous 24-hour shift in labour and delivery. The 24-hour samples were analysed using standard HRV measurements. HRV measurements obtained from each physician were then compared according to shift type, with each physician acting as his or her own comparator. There were no statistically significant differences in the most important measures of HRV between 24-hour periods which included either a 14-hour overnight shift or a continuous 24-hour shift on labour and delivery. We found no significant differences in key HRV measures in obstetricians working 14 hours versus 24 hours in labour and delivery. An anecdotal increase in physician awareness of his/her own health related to working conditions was noted during the study. Future studies should attempt to control for the hours prior to a night shift, assess associated endocrine variations, and focus upon HRV in the post-shift period. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Detection of myocardial viability by means of Single Proton Emission Computed Tomography (Perfused SPECT) dual 201 Tl (rest of 15 minutes, 24 late hours and 24 hours reinjection) and gated-SPECT 99m Tc-SESTAMIBI in effort or stimulation of the coronary reserves

International Nuclear Information System (INIS)

Mendoza V, R.

2004-01-01

The objective of this work was to determine if the images of SPECT 201 TI in rest of 15 minutes, 24 late hours and Gated-SPECT 99m Tc-SESTAMIBI in effort or stimulation of coronary reservation correlate with the study of 24 hours post reinjection of 201 TI to determine the presence of having knitted viable myocardium. Material and methods: 29 patients were studied with coronary arterial illness (EAC) to who are carried out SPECT 201 TI in rest with images of 15 minutes, 24 late hours and 24 hours reinjection, by means of the administration of 201 TI to dose of 130 MBq and reinjection with 37 MBq. and Gated-SPECT 99m Tc-SESTAMIBI in effort or stimulation of coronary reservation, later to the administration of 1110 MBq. Results: 29 patients were included according to inclusion approaches and exclusion, of those which 22 (75.86%) they correspond at the masculine sex and 7 (24.13%) to the feminine one, with an average of 62.1 year-old age, 2320 segments myocardial were analysed so much it is phase post-effort as rest; they were diagnosed a total of 264 segments with heart attack, of which viability myocardium was observed in 174 segments. The statistical tests are analysis of frequencies. The non parametric test of Wilcoxon and Mann-Whitney. Conclusions: the viability myocardial at the 24 late hours and 24 hours reinjection was similar; significant difference exists between the study of 15 minutes and 24 hours reinjection, ischemic illness was also demonstrated in territories different to the heart attack area in the studies of 15 minutes, late 24 hours and 24 hours reinjection. (Author)

Comparison of Measured and Estimated CT Organ Doses for Modulated and Fixed Tube Current:: A Human Cadaver Study.

Science.gov (United States)

Padole, Atul; Deedar Ali Khawaja, Ranish; Otrakji, Alexi; Zhang, Da; Liu, Bob; Xu, X George; Kalra, Mannudeep K

2016-05-01

The aim of this study was to compare the directly measured and the estimated computed tomography (CT) organ doses obtained from commercial radiation dose-tracking (RDT) software for CT performed with modulated tube current or automatic exposure control (AEC) technique and fixed tube current (mAs). With the institutional review board (IRB) approval, the ionization chambers were surgically implanted in a human cadaver (88 years old, male, 68 kg) in six locations such as liver, stomach, colon, left kidney, small intestine, and urinary bladder. The cadaver was scanned with routine abdomen pelvis protocol on a 128-slice, dual-source multidetector computed tomography (MDCT) scanner using both AEC and fixed mAs. The effective and quality reference mAs of 100, 200, and 300 were used for AEC and fixed mAs, respectively. Scanning was repeated three times for each setting, and measured and estimated organ doses (from RDT software) were recorded (N = 3*3*2 = 18). Mean CTDIvol for AEC and fixed mAs were 4, 8, 13 mGy and 7, 14, 21 mGy, respectively. The most estimated organ doses were significantly greater (P < 0.01) than the measured organ doses for both AEC and fixed mAs. At AEC, the mean estimated organ doses (for six organs) were 14.7 mGy compared to mean measured organ doses of 12.3 mGy. Similarly, at fixed mAs, the mean estimated organ doses (for six organs) were 24 mGy compared to measured organ doses of 22.3 mGy. The differences among the measured and estimated organ doses were higher for AEC technique compared to the fixed mAs for most organs (P < 0.01). The most CT organ doses estimated from RDT software are greater compared to directly measured organ doses, particularly when AEC technique is used for CT scanning. Copyright © 2016 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Fixed-dose combinations of drugs versus single-drug formulations for treating pulmonary tuberculosis

Science.gov (United States)

Gallardo, Carmen R; Rigau Comas, David; Valderrama Rodríguez, Angélica; Roqué i Figuls, Marta; Parker, Lucy Anne; Caylà, Joan; Bonfill Cosp, Xavier

2016-01-01

Background People who are newly diagnosed with pulmonary tuberculosis (TB) typically receive a standard first-line treatment regimen that consists of two months of isoniazid, rifampicin, pyrazinamide, and ethambutol followed by four months of isoniazid and rifampicin. Fixed-dose combinations (FDCs) of these drugs are widely recommended. Objectives To compare the efficacy, safety, and acceptability of anti-tuberculosis regimens given as fixed-dose combinations compared to single-drug formulations for treating people with newly diagnosed pulmonary tuberculosis. Search methods We searched the Cochrane Infectious Disease Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL, published in the Cochrane Library, Issue 11 2015); MEDLINE (1966 to 20 November 2015); EMBASE (1980 to 20 November 2015); LILACS (1982 to 20 November 2015); the metaRegister of Controlled Trials; and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), without language restrictions, up to 20 November 2015. Selection criteria Randomized controlled trials that compared the use of FDCs with single-drug formulations in adults (aged 15 years or more) newly diagnosed with pulmonary TB. Data collection and analysis Two review authors independently assessed studies for inclusion, and assessed the risk of bias and extracted data from the included trials. We used risk ratios (RRs) for dichotomous data and mean differences (MDs) for continuous data with 95% confidence intervals (CIs). We attempted to assess the effect of treatment for time-to-event measures with hazard ratios and their 95% CIs. We used the Cochrane 'Risk of bias' assessment tool to determine the risk of bias in included trials. We used the fixed-effect model when there was little heterogeneity and the random-effects model with moderate heterogeneity. We used an I² statistic value of 75% or greater to denote significant heterogeneity, in which case we did not perform a

Comparison of two dose regimens of misoprostol for second-trimester pregnancy termination

NARCIS (Netherlands)

Brouns, Joseph Franciscus Gertrudis Maria; van Wely, Madelon; Burger, Mattheus Petrus Maria; van Wijngaarden, Willem Jacobus

2010-01-01

Objective: The study was conducted to compare the efficacy of two different dose regimens of misoprostol administered vaginally in combination with mifepristone for second trimester termination of viable and non-viable pregnancies. Design: Double-blind randomized controlled trial conducted at the

Bimonthly 24 h infusion of high-dose 5-fluorouracil vs EAP regimen in patients with advanced gastric cancer. A randomized phase II study.

Science.gov (United States)

Popov, I P; Jelić, S B; Krivokapić, Z V; Jezdić, S D; Pesko, P M; Micev, M T; Babić, D R

2008-01-01

To investigate the activity and toxicity of high dose (HD) infusional 5-FU in comparison to EAP regimen as first-line chemotherapy in patients with advanced gastric cancer. Histologically confirmed measurable advanced gastric cancer, age EAP arm: doxorubicin (40 mg/m(2)), etoposide (360 mg/m(2)), and cisplatin (80 mg/m(2)) every 28 d; HD 5-FU arm: 5-FU 2.6 g/m(2) 24 h infusion, biweekly. Sixty patients were randomized. Patient characteristics (arms EAP/HD 5-FU): Median age 57/55 yr, median PS 1/1, LAD (patients) 3/8, M1 (patients) 27/22. Median number of cycles (range): EAP arm 4 (2-8), HD 5-FU arm 2 (1-8). Worst toxicity per cycle (grade 3 and 4 in%): Neutropenia 20/3, thrombocytopenia 9/0, anemia 9/13, diarrhea 3/10, nausea 17/7, vomiting 10/0 for EAP and HD 5-FU arms, respectively. All patients were eligible for response in both arms. Confirmed response rate (95%CI): EAP arm 34% [16-50%]/HD 5-FU arm 10% (0-21%), no change: 46/40%, progression of disease: 20/50, respectively. Overall survival (range): EAP arm A 7 mo [3-27], HD 5-FU arm 6 mo (4-25). Infusional HD 5-FU showed a low incidence of severe toxicity. But given the low efficacy of 5-FU in the dosage we applied in the study, it cannot be recommended as a single treatment for further studies. Assessment of higher dose intensity and/or dose density of 5-FU, with introduction of other active drugs in combination, could be an option for further studies.

COMPARISON OF EFFICACY AND FETOMATERNAL OUTCOME WITH LOW DOSE AND STANDARD PRITCHARD’S REGIMEN OF MAGNESIUM SULPHATE IN ECLAMPSIA

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Nirmala Chamakuri

2017-11-01

Full Text Available BACKGROUND Eclampsia, a hypertensive disorder of pregnancy is a common obstetric emergency, which leads to significant maternal morbidity, perinatal morbidity and mortality. The Pritchard’s regimen of magnesium sulphate remains as the standard regimen worldwide. The aim of this study is to compare the effectiveness, side effects and fetomaternal outcome using low-dose magnesium sulphate with the results of Pritchard regime. MATERIALS AND METHODS A comparative prospective study including 120 eclampsia patients designed into group I and group II treated with low-dose magnesium sulphate and Pritchard’s regimen was conducted in the Department of Obstetrics and Gynaecology for a period of 18 months between January 2015 to June 2016. RESULTS In the present study, there was 100% control of seizures in both the groups. No recurrence of seizures were seen in 57 (95% of cases in group II (low-dose regimen and 3 (5% cases showed recurrence, which were controlled by giving additional doses. In group II, loss of patellar reflexes was seen in 6 (10%, reduced urine output was seen in 3 (5% of cases, mild PPH was observed in 3 (5% cases and perinatal mortality in 18 (30% cases, which were lower than that of group I (Pritchard’s regimen. CONCLUSION Low-dose magnesium sulphate is effective in controlling convulsions in eclampsia. This regimen is highly suitable for use in Indian women who are known to have low body mass index

Effect of travoprost on 24-hour intraocular pressure in normal tension glaucoma

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Yuya Nomura

2010-07-01

Full Text Available Yuya Nomura1, Shunsuke Nakakura2, Mitsuyasu Moriwaki1, Yasuhiro Takahashi1, Kunihiko Shiraki11Department of Ophthalmology and Visual Sciences, Graduate School of Medicine, Osaka City University, Japan; 2Department of Ophthalmology, Saiseikai Gose Hospital, JapanPurpose: The effect of travoprost 0.004% on 24-hour intraocular pressure (IOP was examined in patients with normal tension glaucoma (NTG.Subjects and methods: This study included 17 patients with newly diagnosed unilateral NTG. IOP was measured at three-hour intervals over 24 hours by Goldman applanation tonometer in patients taking topical travoprost 0.004% and was compared retrospectively with 24-hour IOP data in untreated eyes.Results: IOP values were significantly reduced at individual time points after treatment (P < 0.01. Mean 24-hour IOP, maximum 24-hour IOP, minimum 24-hour IOP, and 24-hour IOP fluctuations at baseline (mean ± SD were 12.9 ± 2.2 mmHg, 15.4 ± 2.7 mmHg, 10.5 ± 2.2 mmHg, and 4.9 ± 1.2 mmHg, respectively, and were significantly reduced to 10.3 ± 2.0 mmHg, 12.4 ± 2.5 mmHg, 8.5 ± 1.9 mmHg (all P < 0.001, and 3.9 ± 1.5 mmHg (P < 0.05, respectively, after treatment. The rate of IOP reduction greater than 20% was 58.8% (10 eyes for maximum 24-hour IOP and 53.0% (nine eyes for mean 24-hour IOP.Conclusion: Travoprost reduced IOP throughout the 24-hour study period, with over half of the eyes examined showing IOP reduction exceeding 20%.Keywords: 24-hour intraocular pressure, fluctuation, normal tension glaucoma, travoprost, Travatan Z

Deep venous thrombophlebitis: detection with 4-hour versus 24-hour platelet scintigraphy

International Nuclear Information System (INIS)

Seabold, J.E.; Conrad, G.R.; Ponto, J.A.; Kimball, D.A.; Frey, E.E.; Ahmed, F.; Coughlan, J.D.; Jensen, K.C.

1987-01-01

Thirty-one nonheparinized patients with suspected deep venous thrombophlebitis (DVT) underwent contrast venography and indium-111 platelet scintigraphy (In-111 PS). Venography permitted identification of acute DVT in 12 of 31 cases (39%). One additional patient was considered to have acute DVT despite nonconclusive venography results. In-111 PS results were positive at 4 hours in nine of 13 cases (69%) and at 24 hours in 12 of 13 cases (92%). Two of four patients with false-negative 4-hour In-111 PS studies had received warfarin. Thus, the sensitivity of 4-hour In-111 PS in patients not receiving anticoagulants was 82%. Venography results were negative for acute DVT in 18 cases, and 4-hour In-111 PS studies were negative or equivocal in each. In-111 PS is an alternative to contrast venography for detecting acute DVT. If 4-hour In-111 PS results are positive, anticoagulation can be initiated. Delayed images are necessary if the 4-hour images are negative or equivocal

Long working hours and sickness absence-a fixed effects design.

Science.gov (United States)

Bernstrøm, Vilde Hoff

2018-05-02

While long working hours seem to lead to impaired health, several studies have also shown that long working hours are related to lower levels of sickness absence. Previous studies on the relationship between long working hours and sickness absence have compared those who work long hours to those who do not, looking only at between-individual correlations. Those results might therefore reflect relatively stable differences between employees who typically work long hours and employees who typically do not. The aim of the present study is to examine within-individual correlations between long working hours and sickness absence. Records from the Human Resources department in a large Norwegian hospital from 2012 to 2015 provided objective data on both working hours and sickness absence. Two analyses were performed: a prospective cohort analysis to replicate the results from previous between-individual analyses and a second analysis of within-individual correlations using a fixed effect design. In line with existing research, both between-individual and within-individual analyses showed a negative relationship between long working hours (> 48 h/week) and short-term sickness absence (1-8 days) and no significant difference in incidence of long-term sickness absence (> 8 days). The results indicate that the negative relationship between long working hours and sickness absence is not due only to relatively stable individual differences between those who typically work long hours and those who do not. The results from both analyses therefore still contrast with previous research showing a negative relationship between long working hours and other health indicators.

Prophylactic single-dose administration of 600 mg clindamycin versus 4-time administration of 600 mg clindamycin in orthognathic surgery: A prospective randomized study in bilateral mandibular sagittal ramus osteotomies

NARCIS (Netherlands)

Lindeboom, Jerôme A. H.; Baas, Eric M.; Kroon, Frans H. M.

2003-01-01

Objective. The purpose of this study was to compare a single 600-mg dose of preoperative intravenously administered clindamycin with a 24-hour 600-mg regimen of clindamycin as prophylaxis for postoperative infections in bilateral sagittal ramus osteotomies. Study design. Seventy patients were

Unsupervised/supervised learning concept for 24-hour load forecasting

Energy Technology Data Exchange (ETDEWEB)

Djukanovic, M [Electrical Engineering Inst. ' Nikola Tesla' , Belgrade (Yugoslavia); Babic, B [Electrical Power Industry of Serbia, Belgrade (Yugoslavia); Sobajic, D J; Pao, Y -H [Case Western Reserve Univ., Cleveland, OH (United States). Dept. of Electrical Engineering and Computer Science

1993-07-01

An application of artificial neural networks in short-term load forecasting is described. An algorithm using an unsupervised/supervised learning concept and historical relationship between the load and temperature for a given season, day type and hour of the day to forecast hourly electric load with a lead time of 24 hours is proposed. An additional approach using functional link net, temperature variables, average load and last one-hour load of previous day is introduced and compared with the ANN model with one hidden layer load forecast. In spite of limited available weather variables (maximum, minimum and average temperature for the day) quite acceptable results have been achieved. The 24-hour-ahead forecast errors (absolute average) ranged from 2.78% for Saturdays and 3.12% for working days to 3.54% for Sundays. (Author)

A systematic review of effectiveness and safety of different regimens of levonorgestrel oral tablets for emergency contraception.

Science.gov (United States)

Shohel, Mohammad; Rahman, Mohammad Mahfuzur; Zaman, Asif; Uddin, Mir Muhammad Nasir; Al-Amin, Md Mamun; Reza, Hasan Mahmud

2014-04-04

Unintended pregnancy is a complex phenomenon which raise to take an emergency decision. Low contraceptive prevalence and high user failure rates are the leading causes of this unexpected situation. High user failure rates suggest the vital role of emergency contraception to prevent unplanned pregnancy. Levonorgestrel - a commonly used progestin for emergency contraception. However, little is known about its pharmacokinetics and optimal dose for use. Hence, there is a need to conduct a systematic review of the available evidences. Randomized, double-blind trials were sought, evaluating healthy women with regular menstrual cycles, who requested emergency contraception within 72 h of unprotected coitus, to one of three regimens: 1.5 mg single dose levonorgestrel, two doses of 0.75 mg levonorgestrel given 12 h apart or two doses of 0.75 mg levonorgestrel given 24 h apart. The primary outcome was unintended pregnancy; other outcomes were side-effects and timing of next menstruation. Every trial under consideration successfully established the contraceptive effectiveness of levonorgestrel for preventing unintended pregnancy. Moreover, a single dose of levonorgestrel 1.5 mg for emergency contraception supports its safety and efficacy profile. If two doses of levonorgestrel 0.75 mg are intended for administration, the second dose can positively be taken 12-24 h after the first dose without compromising its contraceptive efficacy. The main side effect was frequent menstrual irregularities. No serious adverse events were reported. The review shows that, emergency contraceptive regimen of single-dose levonorgestrel is not inferior in efficacy to the two-dose regimen. All the regimens studied were very efficacious for emergency contraception and prevented a high proportion of pregnancies if taken within 72 h of unprotected coitus. Single levonorgestrel dose (1.5 mg) can substitute two 0.75 mg doses 12 or 24 h apart. With either regimen, the earlier the treatment is given

Mitigation of Initial Cardiodynamic Effects of the S1P1 Receptor Modulator Ponesimod Using a Novel Up-Titration Regimen.

Science.gov (United States)

Juif, Pierre-Eric; Hoch, Matthias; Vaclavkova, Andrea; Krause, Andreas; Bush, Jim; Dingemanse, Jasper

2017-03-01

Ponesimod, a potent selective sphingosine-1-phosphate receptor 1 modulator, leads to a reduction in circulating total lymphocyte count and transient decreases in heart rate (HR). Based on a modeling and simulation approach, this study was conducted to investigate whether a gradual up-titration regimen may mitigate these cardiodynamic effects. In this double-blind, placebo-controlled, randomized, 2-way crossover study, 32 healthy participants (15 males) received placebo on day 1 followed by multiple-dose administration of either ponesimod or placebo (ratio 3:1). Ponesimod was administered alternately using regimen A (incremental dose increase from 2 to 20 mg in 9 steps) or B (10 mg for 7 days followed by a single-dose administration of 20 mg). Cardiodynamic (Holter and 12-lead ECG), pharmacokinetic, pharmacodynamic (total lymphocyte count), and safety variables were assessed. After first-dose ponesimod administration (day 2), a transient decrease in HR was observed (nadir 2-3 hours postdose, back to predose values within 4-5 hours) of approximately 6 and 12 beats/min (bpm) (mean) following regimens A and B, respectively. On day 2, occurrence of HR 20 ms, was lower following regimen A than B (14 vs 43 events). During the course of the study, incidence of HR <45 bpm was lower following regimen A than B (20 vs 58 events). Fewer participants reported adverse events following regimen A than B. Pharmacokinetics and pharmacodynamics were similar between the regimens. The novel gradual up-titration with ponesimod markedly mitigated initial cardiodynamic effects. © 2016, The American College of Clinical Pharmacology.

Clinical Implications of Complex Pharmacokinetics for Daratumumab Dose Regimen in Patients With Relapsed/Refractory Multiple Myeloma

DEFF Research Database (Denmark)

Xu, Xu Steven; Yan, Xiaoyu; Puchalski, Thomas

2017-01-01

New therapeutic strategies are urgently needed to improve clinical outcomes in patients with multiple myeloma (MM). Daratumumab is a first-in-class, CD38 human immunoglobulin G1κ monoclonal antibody approved for treatment of relapsed or refractory MM. Identification of an appropriate dose regimen...... for daratumumab is challenging due to its target-mediated drug disposition, leading to time- and concentration-dependent pharmacokinetics. We describe a thorough evaluation of the recommended dose regimen for daratumumab in patients with relapsed or refractory MM. This article is protected by copyright. All...

Design of movable fixed area γ dose rate monitor

International Nuclear Information System (INIS)

Li Dongyu; Cheng Wen; Li Jikai; Huang Hong; Shen Qiming; Zhang Qiang; Liu Zhengshan

2005-10-01

Movable fixed area γ dose rate monitor has not only the characteristics of fixed area γ dose rate monitor, but that of portable meter as well. Its main function is to monitor the areas where dose rate would change without orderliness to prevent unplanned radiation exposure accidents from happening. The design way of the monitor, the main indicators description, the working principle and the comprising of software and hardware are briefly introduced. The monitor has the characteristics of simple installation, easy maintenance, little power consumption, wide range, notability of visual and audible alarm and so on. Its design and technique have novelty and advancement. (authors)

Comparison of fixed low dose versus high dose radioactive iodine for the treatment of hyperthyroidism: retrospective multifactorial analysis impacting the outcome of therapy

International Nuclear Information System (INIS)

Suresh Kumar, A.C.; Malhotra, G.; Basu, S.; Asopa, R.V.

2010-01-01

Full text: Radioactive iodine ( 131 I) as a fixed dose protocol is widely used for treatment of hyperthyroidism. However, there is no consensus on the best optimum dose for an individual patient. The objectives of this study were to observe the outcome of 131 I therapy in patients of primary hyperthyroidism in relation to fixed low dose versus high dose regimen, impact of antithyroid drugs and influence of thyroid gland size on therapy outcome. Materials and Methods: Study design: Retrospective analysis. Study group included 287 diagnosed patients of primary hyperthyroidism who had undergone 131 I therapy for the first time (68 M, 219 F; Mean age ± S.D.: 43.84 ± 12.53). All patients with low RAIU, thyrocardiac disease were excluded. Details of antithyroid (ATD) drug treatment were recorded. Analysis was done from 2002 till patients became euthyroid/hypothyroid or until January 2010. Each patient's response was evaluated initially at 6 weeks and thereafter every three months. Appropriate statistical tests were applied to compare treatment response between the groups. A P value<0.05 was considered significant. Results: Of 287 patients, 209 patients had been administered low dose (Mean ± S.D.: 4.68 ± 0.62 mCi) while 78 patients had received high dose (Mean ± S.D.: 9.15 ± 1.05 mCi) of radioiodine. 57.9% (121/ 209) patients in the low dose group responded as compared to 75.6% (59/78) in high dose group after a follow up of more than 36 months. Similarly, among patients with and without antithyroid drug treatment, grade II and above goiters the response rates were significantly higher for high dose group as compared to low dose group. Conclusion: We suggest that high dose radioiodine treatment with 8 to 10 mCi is effective in treating hyperthyroidism in patients with a better success rate than the low dose treatment with 3 to 5 mCi. This is also likely to be helpful in patients who have not received antithyroid drugs. It appears that clinically relevant

The 24-Hour Mathematical Modeling Challenge

Science.gov (United States)

Galluzzo, Benjamin J.; Wendt, Theodore J.

2015-01-01

Across the mathematics curriculum there is a renewed emphasis on applications of mathematics and on mathematical modeling. Providing students with modeling experiences beyond the ordinary classroom setting remains a challenge, however. In this article, we describe the 24-hour Mathematical Modeling Challenge, an extracurricular event that exposes…

Co-extrusion as a processing technique to manufacture a dual sustained release fixed-dose combination product.

Science.gov (United States)

Vynckier, An-Katrien; Voorspoels, Jody; Remon, Jean Paul; Vervaet, Chris

2016-05-01

This study aimed to design a fixed-dose combination dosage form which provides a sustained release profile for both the freely water-soluble metformin HCl and the poorly soluble gliclazide, two antidiabetic compounds used to treat diabetes mellitus. Hot-melt co-extrusion was used as an innovative manufacturing technique for a pharmaceutical fixed-dose combination product. In this way, a matrix formulation that sustained metformin release could be developed, despite the high drug load in the formulation and the freely soluble nature of the drug. It was clear that co-extrusion was perfectly suited to produce a fixed-dose combination product with adequate properties for each of the incorporated APIs. A coat layer, containing at least 30% CAPA(®) 6506 as a hydrophobic polymer, was necessary to adequately sustain the release of the highly dosed freely soluble drug from the 70% metformin HCl-loaded CAPA(®) 6506 core of the co-extrudate. To obtain a complete gliclazide release over 24-h solubilization in Kollidon(®) VA, added as a second polymer to the CAPA(®) 6506 in the coat, was needed. Both active pharmaceutical ingredients (APIs), which have different physicochemical characteristics, were formulated in a single dosage form, using co-extrusion. © 2016 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology.

Effectiveness and Safety of Generic Fixed-Dose Combination of Tenofovir/Emtricitabine/Efavirenz in HIV-1-Infected Patients in Western India.

Science.gov (United States)

Pujari, Sanjay; Dravid, Ameet; Gupte, Nikhil; Joshix, Kedar; Bele, Vivek

2008-08-20

To assess effectiveness and safety of a generic fixed-dose combination of tenofovir (TDF)/emtricitabine (FTC)/efavirenz (EFV) among HIV-1-infected patients in Western India. Antiretroviral (ARV)-naive and experienced (thymidine analog nucleoside reverse transcriptase inhibitor [tNRTI] replaced by TDF) patients were started on a regimen of 1 TDF/FTC/EFV pill once a day. They were followed clinically on a periodic basis, and viral loads and CD4 counts were measured at 6 and 12 months. Creatinine clearance was calculated at baseline and at 6 months and/or as clinically indicated. Effectiveness was defined as not having to discontinue the regimen due to failure or toxicity. One hundred forty-one patients who started TDF/FTC/EFV before 1 June 2007 were eligible. Of these, 130 (92.2%) and 44 (31.2%) had 6- and 12-months follow-up, respectively. Thirty-five percent of the patients were ARV-naive. Eleven patients discontinued treatment (4 for virologic failure, 1 for grade 3-4 central nervous system disturbances, 4 for grade 3-4 renal toxicity, and 2 for cost). Ninety-six percent of patients were virologically suppressed at 6 months. Frequency of TDF-associated grade 3-4 renal toxicity was 2.8%; however, 3 of these patients had comorbid conditions associated with renal dysfunction. A fixed-dose combination of generic TDF/FTC/EFV is effective in ARV-naive and experienced patients. Although frequency of severe renal toxicity was higher than has been reported in the literature, it was safe in patients with no comorbid renal conditions.

[Considerations about the efficiency of treatment regimens with fixed Rifampicin-Isoniazid combinations in pulmonary tuberculosis].

Science.gov (United States)

Munteanu, Ioana; Husar, Iulia; Didilescu, C; Stoicescu, I P

2004-01-01

Here are presented the results of a prospective, randomized study regarding the efficiency of regimens with fixed drug combination Rifampicin-Isoniazide manufactured by Antibiotics S.A. of Iasi in comparison with single drugs routinely used in treatment of patients with pulmonary tuberculosis. Newly diagnosed (confirmed by smear and culture) pulmonary tuberculosis patients were selected, and those who accepted to be included in the study, were admitted to the National Institute of Pneumology "Marius Nasta" between August 2001 and September 2002. At the time of admission, they were randomized into two groups: 20 patients received fixed drug combination RMP300 HIN150, and 18 patients received RMP and HIN in single drug tablets (2 patients were excluded). The follow-up of the patients was for one year from the date of enclosure. The smear conversion rate was 83,3% for the patients using single drug tablets, and 70% for those using fixed drug combination, motivated with some more severe TB patterns. The success rate was 100% for all TB patients. Although the present study was done for few patients, we can say that it demonstrated the same efficiency of fixed drug combination produced in Romania, with the single drug tablets, and it suggests a better compliance to treatment with a lower price.

The combined fixed-dose antituberculous drugs alter some reproductive functions with oxidative stress involvement in wistar rats

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O. Awodele, B.Pharm M.Sc MPH PhD D.Sc FPCPharm FASI

Full Text Available The reproductive toxicity of combined fixed-dose first-line antituberculosis (CFDAT regimen was assessed in rats. Thirty-two (32 Wistar rats weighing 168.1 ± 8.0 g were divided into four groups of eight rats per group. Two groups of male and female rats were administered oral distilled water (1.6 ml and CFDAT drugs containing rifampicin, isoniazid, pyrazinamide and ethambutol (RIPE, 92.5 mg/m2 per body surface area respectively for forty-five days. Serum follicle stimulating hormone, luteinizing and testosterone were reduced significantly (p  0.05 levels in the treated females. In addition, RIPE reduced (p < 0.05 total proteins levels and increased (p < 0.05, 53% catalase levels in male but not female animals. Superoxide dismutase, glutathione-S-transferase, glutathione peroxidase, reduced glutathione levels as well as lipid peroxidation were unaltered in all rats respectively. Histopathological studies revealed congested peritesticular vessels and no changes in the ovary when compared with control. Overall, our results demonstrate reproductive toxicity potentials of RIPE in the rat, thus, suggesting that these reproductive parameters be monitored during antituberculous chemotherapy. Keywords: Fixed dose combined antituberculous drugs, Sub-chronic study, Reproductive toxicity, Rats

Sleep, 24-hour activity rhythms, and brain structure : A population-based study

NARCIS (Netherlands)

L.A. Zuurbier (Lisette)

2016-01-01

markdownabstractIn this thesis, Chapter 2 focuses on sleep, 24-hour activity rhythms and health. Chapter 2.1 describes the influence of demographics, lifestyle and sleep on 24-hour activity rhythms. In Chapter 2.2 sleep and 24-hour activity rhythms are used to predict mortality. This chapter is

New Advantage 24 contraceptive gel claims 24-hour effectiveness. But proposed FDA rule could put N-9 products to the test.

Science.gov (United States)

1995-04-01

Advantage 24 is a new contraceptive gel that makes use of bioadhesive technology to offer 24 hours of protection relying on the spermicide nonoxynol-9 (N-9) in lower concentrations. If a proposed US Food and Drug Administration (FDA) rule is enforced N-9 may be examined closely. The manufacturer, Whitehall-Robins Healthcare in New Jersey, stopped production of the Today contraceptive sponge because of the costs of complying with FDA standards. The Advantage 24 gel costs twice as much as the sponge. It is made in Switzerland and distributed by an Illinois company. Any vaginal contraceptive containing N-9 would be approved by the FDA as long as it complied with guidelines laid down in an FDA monograph. However, the registration of the gel could not be confirmed. The product uses a bioadhesive technology concept that natural substances adhere to epithelial and mucosal tissues in the body. Polycarbofil is mixed with water, N-9, and mineral oil to create an emulsion that allows for a time-release mechanism, but at any given time only 2 mg of N-9 is available to kill sperm. The final formula for Advantage 24 is 52.5 mg per dose. Too much N-9 can be toxic, as demonstrated by the Today sponge, which contained 1000 mg of N-9. In Kenya prostitutes using it frequently experienced 3 times as many genital lesions as those using a placebo. A study of Advantage 24 by a Miami laboratory involved 250 women, 22-45 years old, who had had prior tubal ligations. When the gel was applied 15-30 minutes before intercourse the efficacy rate was 98%; it was 91% for those applying it 12 hours before; and it was 86% when the gel was applied 24 hours ahead of time. FDA compliance officers are intrigued about the claim that the gel lasts 24 hours. However, if the claim is held up by research data, women will have an easily available, portable, efficient, aesthetic, and highly effective contraceptive.

Comparison of two dose regimens of growth hormone (GH) with different target IGF-1 levels on glucose metabolism, lipid profile, cardiovascular function and anthropometric parameters in gh-deficient adults.

Science.gov (United States)

Cenci, Maria Claudia Peixoto; Soares, Débora Vieira; Spina, Luciana Diniz Carneiro; Brasil, Rosane Resende de Lima Oliveira; Lobo, Priscila Marise; Michmacher, Eduardo; Vaisman, Mario; Boguszewski, Cesar Luiz; Conceição, Flávia Lúcia

2012-01-01

To compare the effects of two regimens of GH therapy with different target IGF-1 levels on anthropometric parameters, glucose metabolism, lipid profile and cardiac function in adults with GH deficiency (GHD). Retrospective analysis of 14 GHD adults from Clementino Fraga Filho University Hospital, Rio de Janeiro, Brazil, who were treated with a GH regimen aimed at maintaining serum IGF-1 levels between the median and upper reference limit (high dose group - HDGH) and 18 GHD adults from Federal University Hospital, Curitiba, Brazil, who received a fixed GH dose of 0.2mg/day in the first year of treatment, followed by titration to maintain serum IGF-1 levels between the median and lower reference limit (low dose group - LDGH). All patients were followed for 2 years with analysis of anthropometric parameters, serum levels of IGF-1, glucose, insulin, HOMA-IR, lipid profile, and transthoracic echocardiography. Changes on weight, BMI and waist circumference were similar between the two groups. Insulin levels increased and HOMA-IR worsened in the LDGH group at 1year and improved thereafter. Total cholesterol and triglycerides did not change with therapy. LDL cholesterol reduced in both groups, while HDL-cholesterol significantly increased only in the HDGH group (p=0.007 vs LDGH). No significant variations on echocardiographic parameters were observed. The HDGH and LDGH regimens resulted in similar changes on anthropometric, echocardiographic, glucose and lipid parameters in GHD adults, except for increase in HDL cholesterol that was only observed in the HDGH regimen. Copyright © 2012 Elsevier Ltd. All rights reserved.

Efficacy and safety of various repeat treatment dosing regimens of rituximab in patients with active rheumatoid arthritis: results of a Phase III randomized study (MIRROR)

NARCIS (Netherlands)

Rubbert-Roth, Andrea; Tak, Paul P.; Zerbini, Cristiano; Tremblay, Jean-Luc; Carreño, Luis; Armstrong, Gillian; Collinson, Neil; Shaw, Tim M.

2010-01-01

Methods. Patients with active RA despite stable MTX (10-25 mg/week) were randomly assigned to one of the three treatment regimens comprising two courses of RTX given 24 weeks apart: 2 x 500 and 2 x 500 mg; 2 x 500 and 2 x 1000 mg (dose escalation); and 2 x 1000 and 2 x 1000 mg. The primary endpoint

A novel approach to pharmacodynamic assessment of antimicrobial agents: new insights to dosing regimen design.

Directory of Open Access Journals (Sweden)

Vincent H Tam

Full Text Available Pharmacodynamic modeling has been increasingly used as a decision support tool to guide dosing regimen selection, both in the drug development and clinical settings. Killing by antimicrobial agents has been traditionally classified categorically as concentration-dependent (which would favor less fractionating regimens or time-dependent (for which more frequent dosing is preferred. While intuitive and useful to explain empiric data, a more informative approach is necessary to provide a robust assessment of pharmacodynamic profiles in situations other than the extremes of the spectrum (e.g., agents which exhibit partial concentration-dependent killing. A quantitative approach to describe the interaction of an antimicrobial agent and a pathogen is proposed to fill this unmet need. A hypothetic antimicrobial agent with linear pharmacokinetics is used for illustrative purposes. A non-linear functional form (sigmoid Emax of killing consisted of 3 parameters is used. Using different parameter values in conjunction with the relative growth rate of the pathogen and antimicrobial agent concentration ranges, various conventional pharmacodynamic surrogate indices (e.g., AUC/MIC, Cmax/MIC, %T>MIC could be satisfactorily linked to outcomes. In addition, the dosing intensity represented by the average kill rate of a dosing regimen can be derived, which could be used for quantitative comparison. The relevance of our approach is further supported by experimental data from our previous investigations using a variety of gram-negative bacteria and antimicrobial agents (moxifloxacin, levofloxacin, gentamicin, amikacin and meropenem. The pharmacodynamic profiles of a wide range of antimicrobial agents can be assessed by a more flexible computational tool to support dosing selection.

Vitamin D supplementation in nursing home patients: randomized controlled trial of standard daily dose versus individualized loading dose regimen.

Science.gov (United States)

Wijnen, Hugo; Salemink, Dayenne; Roovers, Lian; Taekema, Diana; de Boer, Hans

2015-05-01

Supplementation of cholecalciferol 800 IU daily appears to be insufficient to raise vitamin D levels to >75 nmol/l in nursing home (NH) patients. Our objective was to compare the efficacy of an individualized cholecalciferol loading dose (LD) regimen and a daily dose (DD) regimen of cholecalciferol 800 IU in reaching 25-OH vitamin D (25OHD) levels >75 nmol/l. A total of 30 NH patients with 25OHD levels 50 nmol/l were included. Patients were randomized using the minimization method in the LD or DD group. The cholecalciferol LD, calculated with an algorithm based on serum 25OHD level and body weight, was administered in divided doses of 50,000 IU twice a week, followed by a monthly maintenance dose of either 50,000 or 25,000 IU. The DD regimen consisted of cholecalciferol 800 IU daily for 26 weeks. Serum 25OHD, calcium, creatinine, phosphate, and parathyroid hormone were measured, and 2-minute walking test, handgrip strength, and timed get up and go test were assessed at baseline (T 0), after 5 weeks (T 5), 12 weeks (T 12), and 26 weeks (T 26). The primary endpoint was the percentage of patients with 25OHD levels >75 nmol/l at T 5. Secondary endpoints were the proportion of patients with 25OHD levels >75 nmol/l at T 26, safety of LD regimen, and improvement of performance tests with normalization of vitamin D levels. Median baseline 25OHD levels (interquartile range) were comparable between the 14 DD and 16 LD patients: 20.9 (15.9-29.6) and 21.7 (16.4-32.8) nmol/l, respectively. Levels of 25OHD >75 nmol/l at T 5 were reached in 79 % of the 14 LD patients, but in none of the 13 DD patients (p 75 nmol/l were reached in 83 % of the 12 LD patients and in 30 % of the ten DD patients (p tests was observed. In NH patients with severe 25OHD deficiency, an individualized calculated cholecalciferol LD is likely to be superior to a DD of cholecalciferol 800 IU in terms of the ability to rapidly normalize vitamin D levels.

Effect of overtime work on 24-hour ambulatory blood pressure.

Science.gov (United States)

Hayashi, T; Kobayashi, Y; Yamaoka, K; Yano, E

1996-10-01

Recently, the adverse effects of long working hours on the cardiovascular systems of workers in Japan, including "Karoshi" (death from overwork), have been the focus of social concern. However, conventional methods of health checkups are often unable to detect the early signs of such adverse effects. To evaluate the influence of overtime work on the cardiovascular system, we compared 24-hour blood pressure measurements among several groups of male white-collar workers. As a result, for those with normal blood pressure and those with mild hypertension, the 24-hour average blood pressure of the overtime groups was higher than that of the control groups; for those who periodically did overtime work, the 24-hour average blood pressure and heart rate during the busy period increased. These results indicate that the burden on the cardiovascular system of white-collar workers increases with overtime work.

Analysis of 24-hour versus 48-hour traffic counts for HPMS sampling.

Science.gov (United States)

2014-04-01

The Illinois Department of Transportation (IDOT) has requested a waiver from the Federal Highway Administration (FHWA) to : allow IDOT to implement a 24-hour traffic-count program on the non-state HPMS routes, as opposed to the current Highway : Perf...

Pain Levels Within 24 Hours After UFE: A Comparison of Morphine and Fentanyl Patient-Controlled Analgesia

International Nuclear Information System (INIS)

Kim, Hyun S.; Czuczman, Gregory J.; Nicholson, Wanda K.; Pham, Luu D.; Richman, Jeffrey M.

2008-01-01

The purpose of this study was to assess the presence and severity of pain levels during 24 h after uterine fibroid embolization (UFE) for symptomatic leiomyomata and compare the effectiveness and adverse effects of morphine patient-controlled analgesia (PCA) versus fentanyl PCA. We carried out a prospective, nonrandomized study of 200 consecutive women who received UFE and morphine or fentanyl PCA after UFE. Pain perception levels were obtained on a 0-10 scale for the 24-h period after UFE. Linear regression methods were used to determine pain trends and differences in pain trends between two groups and the association between pain scores and patient covariates. One hundred eighty-five patients (92.5%) reported greater-than-baseline pain after UFE, and 198 patients (99%) required IV opioid PCA. One hundred thirty-six patients (68.0%) developed nausea during the 24-h period. Seventy-two patients (36%) received morphine PCA and 128 (64%) received fentanyl PCA, without demographic differences. The mean dose of morphine used was 33.8 ± 26.7 mg, while the mean dose of fentanyl was 698.7 ± 537.4 μg. Using this regimen, patients who received morphine PCA had significantly lower pain levels than those who received fentanyl PCA (p < 0.0001). We conclude that patients develop pain requiring IV opioid PCA within 24 h after UFE. Morphine PCA is more effective in reducing post-uterine artery embolization pain than fentanyl PCA. Nausea is a significant adverse effect from opioid PCA.

Epidemiology of hyperbilirubinemia in the first 24 hours after birth

Directory of Open Access Journals (Sweden)

Zarrinkoub F

2007-09-01

Full Text Available   Background: Jaundice is one of the most frequent problems observed in newborns. Our purpose was to investigate the incidence and the risk factors on jaundice noted in the first 24 hours after birth.Methods: All newborns observed to have jaundice within the first 24 hours after birth were enrolled prospectively in this study. Laboratory evaluations included blood group typing of mother and newborn, hemoglobin and hematocrit, complete blood count, peripheral blood smear, reticulocyte count, G6PD activity, maternal indirect and neonatal direct Coombs test, and serum total, conjugated, and unconjugated bilirubin. In all cases, gender, birth weight, Apgar scores, gestational age, mode of delivery, birth trauma, cephalhematoma, maternal age, parity, or any siblings with neonatal jaundice were recorded. Data were analyzed using one-way ANOVA, Student's t-, and chi-square tests.Results: Of a total of 2096 newborns delivered in one year, 122 (5.8% developed jaundice within the first 24 hours after birth. Risk factors for hyperbilirubinemia were ABO incompatibility, prematurity, infection, G6PD deficiency, cephalhematoma, asphyxia, and Rh disease. There were no statistically significant relationships between jaundice and maternal age, parity, mode of delivery, neonatal gender or previous siblings with jaundice (p>0.05.Conclusions: Jaundice observed in the initial 24 hours after birth was infrequent, but clinically significant. All newborns should be followed by repeated exams within the first 24 hours after birth and before discharge, especially if the maternal blood group is O.

Office and ambulatory blood pressure control with a fixed-dose combination of candesartan and hydrochlorothiazide in previously uncontrolled hypertensive patients: results of CHILI CU Soon

Directory of Open Access Journals (Sweden)

Bramlage P

2011-12-01

Full Text Available Thomas Mengden1, Reinhold Hübner2, Peter Bramlage31Kerckhoff-Klinik GmbH, Bad Nauheim, 2Takeda Pharma GmbH, Aachen, 3Institut für Kardiovaskuläre Pharmakologie und Epidemiologie, Mahlow, GermanyBackground: Fixed-dose combinations of candesartan 32 mg and hydrochlorothiazide (HCTZ have been shown to be effective in clinical trials. Upon market entry we conducted a noninterventional study to document the safety and effectiveness of this fixed-dose combination in an unselected population in primary care and to compare blood pressure (BP values obtained during office measurement (OBPM with ambulatory blood pressure measurement (ABPM.Methods: CHILI CU Soon was a prospective, noninterventional, noncontrolled, open-label, multicenter study with a follow-up of at least 10 weeks. High-risk patients aged ≥18 years with previously uncontrolled hypertension were started on candesartan 32 mg in a fixed-dose combination with either 12.5 mg or 25 mg HCTZ. OBPM and ABPM reduction and adverse events were documented.Results: A total of 4131 patients (52.8% male with a mean age of 63.0 ± 11.0 years were included. BP was 162.1 ± 14.8/94.7 ± 9.2 mmHg during office visits at baseline. After 10 weeks of candesartan 32 mg/12.5 mg or 25 mg HCTZ, mean BP had lowered to 131.7 ± 10.5/80.0 ± 6.6 mmHg (P < 0.0001 for both comparisons. BP reduction was comparable irrespective of prior or concomitant medication. In patients for whom physicians regarded an ABPM to be necessary (because of suspected noncontrol over 24 hours, ABP at baseline was 158.2/93.7 mmHg during the day and 141.8/85.2 mmHg during the night. At the last visit, BP had significantly reduced to 133.6/80.0 mmHg and 121.0/72.3 mmHg, respectively, resulting in 20.8% being normotensive over 24 hours (<130/80 mmHg. The correlation between OBPM and ABPM was good (r = 0.589 for systolic BP and r = 0.389 for diastolic BP during the day. Of those who were normotensive upon OBPM, 35.1% had high ABPM during the

Compliance, Safety, and Effectiveness of Fixed-Dose Artesunate-Amodiaquine for Presumptive Treatment of Non-Severe Malaria in the Context of Home Management of Malaria in Madagascar

Science.gov (United States)

Ratsimbasoa, Arsène; Ravony, Harintsoa; Vonimpaisomihanta, Jeanne-Aimée; Raherinjafy, Rogelin; Jahevitra, Martial; Rapelanoro, Rabenja; Rakotomanga, Jean De Dieu Marie; Malvy, Denis; Millet, Pascal; Ménard, Didier

2012-01-01

Home management of malaria is recommended for prompt, effective antimalarial treatment in children less than five years of age. Compliance, safety, and effectiveness of the new fixed-dose artesunate-amodiaquine regimen used to treat suspected malaria were assessed in febrile children enrolled in a 24-month cohort study in two settings in Madagascar. Children with fever were asked to visit community health workers. Presumptive antimalarial treatment was given and further visits were scheduled for follow-up. The primary endpoint was the risk of clinical/parasitologic treatment failure. Secondary outcomes included fever/parasite clearance, change in hemoglobin levels, and frequency of adverse events. The global clinical cure rate was 98.4% by day 28 and 97.9% by day 42. Reported compliance was 83.4%. No severe adverse effects were observed. This study provides comprehensive data concerning the clinical cure rate obtained with artesunate-amodiaquine and evidence supporting the scaling up of home management of malaria. PMID:22302849

In-home HIV testing and nevirapine dosing by traditional birth attendants in rural Zambia: a feasibility study.

Science.gov (United States)

Brennan, Alana T; Thea, Donald M; Semrau, Katherine; Goggin, Caitlin; Scott, Nancy; Pilingana, Portipher; Botha, Belinda; Mazimba, Arthur; Hamomba, Leoda; Seidenberg, Phil

2014-01-01

Access to lifesaving prevention of mother-to-child transmission (PMTCT) services is problematic in rural Zambia. The simplest intervention used in Zambia has been 2-dose nevirapine (NVP) administration in the peripartum period, a regimen of 1 NVP tablet to the mother at the onset of labor and 1 dose in the form of syrup to the newborn within 4 to 72 hours after birth. This 2-dose regimen has been shown to reduce MTCT by nearly 50%. We set out to demonstrate that in-home HIV testing and NVP dosing by traditional birth attendants (TBAs) is feasible and acceptable by women in rural Zambia. This was a pilot program using TBAs to perform rapid saliva-based HIV testing and administer single-dose NVP in tablet form to the mother at the onset of labor and syrup to the infant after birth. A total of 280 pregnant women were consented and enrolled into the program, of whom 124 (44.3%) gave birth at home with the assistance of a trained TBA. Of those, 16 (12.9%) were known to be HIV positive, and 101 of the remaining 108 (93.5%) accepted a rapid HIV test. All these women tested HIV negative. In the subset of 16 mothers who were HIV positive, 13 (81.3%) took single-dose NVP administered by a TBA between 1 and 24 hours prior to birth and 100% of exposed newborns (16 of 16) received NVP syrup within 72 hours after birth, 80% of whom were dosed in the first 24 hours of life. With the substantial shortage of human resources in public health care throughout sub-Saharan Africa, it is extremely valuable to utilize lay health care workers to help extended services beyond the level of the facility. Given the high uptake of PMTCT services we believe that TBAs with proper training and support can successfully provide country-approved PMTCT. © 2013 by the American College of Nurse-Midwives.

Three different up-titration regimens of ponesimod, an S1P1 receptor modulator, in healthy subjects.

Science.gov (United States)

Scherz, Michael W; Brossard, Patrick; D'Ambrosio, Daniele; Ipek, Murat; Dingemanse, Jasper

2015-06-01

Ponesimod is a selective S1P1 receptor modulator, and induces dose-dependent reduction of circulating lymphocytes upon oral dosing. Previous studies showed that single doses up to 75 mg or multiple doses up to 40 mg once daily are well tolerated, and heart rate (HR) reduction and atrio-ventricular conduction delays upon treatment initiation are reduced by gradual up-titration to the maintenance dose. This single-center, open-label, randomized, multiple-dose, 3-treatment, 3-way crossover study compared the tolerability, safety, pharmacokinetics, cardiodynamics, and effects on lymphocytes of 3 different up-titration regimens of ponesimod in healthy male and female subjects. Up-titration regimens comprised escalating periods of b.i.d. dosing (2.5 or 5 mg) and q.d. dosing (10 or 20 mg or both). After the third up-titration period a variable-duration washout period of 1-3 days was followed by re-challenge with a single 20-mg dose of ponesimod. Adverse events were transient and mild to moderate in intensity, not different between regimens. HR decrease after the first dose was greater than after all subsequent doses, including up-titration doses. Little or no HR change was observed with morning doses of b.i.d. regimens, suggesting that 2.5 and 5 mg b.i.d. are sufficient to sustain cardiac desensitization for the 12-hours dosing interval. © 2015, The American College of Clinical Pharmacology.

Single fixed-dose oral dexketoprofen plus tramadol for acute postoperative pain in adults.

Science.gov (United States)

Derry, Sheena; Cooper, Tess E; Phillips, Tudor

2016-09-22

the maximum possible pain relief over six hours, the median time to use of rescue medication, and the proportion of participants requiring rescue medication. We also collected information on adverse events and withdrawals. We assessed the quality of the evidence using GRADE and created a 'Summary of findings' table.We also collected information on the number of participants with at least 50% of the maximum possible pain relief over six hours for dexketoprofen alone and tramadol alone. We included three studies with 1853 participants who had undergone surgical removal of impacted wisdom teeth, hip replacement, or hysterectomy. The overall risk of bias across the three included studies was low, with unclear risk of bias in relation to the size of the three studies. Two studies did not report all our prespecified outcomes, which limited the analyses we could do.The proportion of participants achieving at least 50% pain relief over six hours with dexketoprofen 25 mg plus tramadol 75 mg was 66%, compared to 32% with placebo, giving an NNT of 3.0 (95% CI 2.5 to 3.7) (RR 2.1 (95% CI 1.7 to 2.4); 748 participants; 3 studies) (moderate quality evidence). The response rate with dexketoprofen 25 mg alone was 53% (RR 1.3 (95% CI 1.1 to 1.4); 744 participants; 3 studies) and with tramadol alone was 45% (RR 1.5 (95% CI 1.3 to 1.7); 741 participants; 3 studies) (moderate quality evidence). We downgraded the evidence because of some inconsistency in the results.The median time to use of rescue medication could not be estimated exactly, but was probably eight hours or more, indicating a long duration of effect (moderate quality evidence). We downgraded the evidence because it was not possible to estimate the effect exactly in the two multiple dose studies, resulting in imprecision. Fewer participants used rescue medication with higher doses of active treatment (summary statistic not calculated; 123 participants; 1 study) (very low quality evidence). We downgraded the evidence because

Comparison of anthropometric and training characteristics between recreational male marathoners and 24-hour ultramarathoners.

Science.gov (United States)

Rüst, Christoph Alexander; Knechtle, Beat; Knechtle, Patrizia; Rosemann, Thomas

2012-01-01

Of the anthropometry and training variables used to predict race performance in a 24-hour ultrarun, the personal best marathon time is the strongest predictor in recreational male 24-hour ultramarathoners. This finding raises the question of whether similarities exist between male recreational 24-hour ultramarathoners and male recreational marathoners. The association between age, anthropometric variables (ie, body mass, body height, body mass index, percent body fat, skeletal muscle mass, limb circumference, and skinfold thickness at the pectoral, mid axillary, triceps, subscapular, abdominal, suprailiac, front thigh, and medial calf sites), previous experience and training characteristics (ie, volume, speed, and personal best time), and race time for 79 male recreational 24-hour ultramarathoners and 126 male recreational marathoners was investigated using bivariate and multivariate analysis. The 24-hour ultramarathoners were older (P marathoners. During training, the 24-hour ultramarathoners were running for more hours per week (P marathoners. In the 24-hour ultramarathoners, neither anthropometric nor training variables were associated with kilometers completed in the race (P > 0.05). In the marathoners, percent body fat (P marathon race times. In summary, differences in anthropometric and training predictor variables do exist between male recreational 24-hour ultramarathoners and male recreational marathoners for race performance.

An Hourly Dose-Escalation Desensitization Protocol for Aspirin-Exacerbated Respiratory Disease.

Science.gov (United States)

Chen, Justin R; Buchmiller, Brett L; Khan, David A

2015-01-01

Aspirin desensitization followed by maintenance therapy effectively improves symptom control in patients with aspirin exacerbated respiratory disease (AERD). The majority of current desensitization protocols use 3-hour dosing intervals and often require 2 to 3 days to complete. We evaluated hourly dose escalations in a subset of patients with chronic rhinosinusitis, nasal polyps, and asthma who historically reacted to aspirin within 1 hour or were avoiding aspirin with the goal of developing a safe and efficient desensitization protocol. Fifty-seven aspirin desensitizations were performed under the hourly protocol. All patients had refractory nasal polyposis as an indication for aspirin desensitization. The clinical characteristics of each subject were analyzed in relation to aspects of his or her reactions during the procedure. Ninety-eight percent of study patients were successfully treated under the hourly protocol, including those with a history of severe reactions and intubation. None required further medication than is available in an outpatient allergy clinic. A total of 96% of reactors recorded a bronchial or naso-ocular reaction within 1 hour of the preceding dose. Of the total patients on this protocol, 40% were able to complete the procedure in a single day, and 60% within 2 days. Patients with AERD who have a history of symptoms less than 1 hour after aspirin exposure can be safely desensitized with a 1-hour dose-escalation protocol that can often be completed in a single day. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Optimising glucocorticoid replacement therapy in severely adrenocorticotropin (ACTH) deficient hypopituitary male patients.

LENUS (Irish Health Repository)

Behan, Lucy-Ann

2011-04-18

Context:  The optimal replacement regimen of hydrocortisone in adults with severe ACTH deficiency remains unknown. Management strategies vary from treatment with 15mg to 30mg or higher in daily divided doses, reflecting the paucity of prospective data on the adequacy of different glucocorticoid regimens. Objective:  Primarily to define the hydrocortisone regimen which results in a 24hour cortisol profile that most closely resembles that of healthy controls and secondarily to assess the impact on quality of life (QoL). Design:  10 male hypopituitary patients with severe ACTH deficiency (basal cortisol <100nM and peak response to stimulation <400nM) were enrolled in a prospective, randomised, crossover study of 3 hydrocortisone dose regimens. Following 6 weeks of each regimen patients underwent 24hour serum cortisol sampling and QoL assessment with the Short Form 36 and the Nottingham Health Profile questionnaires. Free cortisol was calculated using Coolen\\'s equation. All results were compared to those of healthy, matched controls. Results:  CBG was significantly lower across all dose regimens compared to controls (p<0.05). The lower dose regimen C(10mg mane\\/5mg tarde) produced a 24hour free cortisol profile which most closely resembled that of controls. Both regimen A(20mg mane\\/10mg tarde) and B(10mg mane\\/10mg tarde) produced supraphysiological post-absorption peaks. There was no significant difference in QoL in patients between the three regimens, however energy level was significantly lower across all dose regimens compared to controls (p<0.001). Conclusions:  The lower dose of HC(10mg\\/5mg) produces a more physiological cortisol profile, without compromising quality of life, compared to higher doses still used in clinical practice. This may have important implications in these patients, known to have excess cardiovascular mortality.

Comparable Renal Function at 6 Months with Tacrolimus Combined with Fixed-Dose Sirolimus or MMF: Results of a Randomized Multicenter Trial in Renal Transplantation

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Eveline Van Gurp

2010-01-01

Full Text Available In a multicenter trial, renal transplant recipients were randomized to tacrolimus with fixed-dose sirolimus (Tac/SRL, N = 318 or tacrolimus with MMF (Tac/MMF, N = 316. Targeted tacrolimus trough levels were lower in the Tac/SRL group after day 14. The primary endpoint was renal function at 6 months using creatinine clearance (Cockcroft-Gault and was comparable at 66.4 mL/min (SE 1.4 with Tac/SRL and at 65.2mL/min (SE 1.3 with Tac/MMF (completers. Biopsy-confirmed acute rejection was 15.1% (Tac/SRL and 12.3% (Tac/MMF. In both groups, graft survival was 93% and patient survival was 99.0%. Premature withdrawal due to an adverse event was twice as high in the Tac/SRL group, 15.1% versus 6.3%. Hypercholesterolemia incidence was higher with Tac/SRL (P30 consecutive days in previously nondiabetic patients was 17.8%, Tac/SRL, and 24.8%, Tac/MMF. Evaluation at 6 months showed comparable renal function using tacrolimus/sirolimus and tacrolimus/MMF regimens.

Evaluation of the Basedow disease treatment by a iodine 131 fixed dose; Evaluation du traitement de la maladie de Basedow par une dose fixe d'iode 131

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El Ajmi, W.; Slim, I; Rmadi, S.; Yeddes, I.; Krimi, S.; Ltaief, B.; Mhiri, A.; Ben Slimene, M.F. [Service de medecine nucleaire, institut Salah Azeiz, Tunis, (Tunisia)

2009-05-15

The treatment of the basedow disease by iodine 131 is more and more used. however, the doses used stay variable. In order to reduce the treatment failure, we chose a protocol with strong fix doses of iodine 131. We give our preliminary results for 63 patients. The treatment by strong fix dose of iodine 131 is simple, safe and efficient for the control of hyperthyroidism in the Basedow disease. This protocol has for advantage to be simpler comparatively to these ones using adjusted doses according the weight of the thyroid and its fixation rate. (N.C.)

Meeting the Canadian 24-Hour Movement Guidelines for Children and Youth.

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Roberts, Karen C; Yao, Xiaoquan; Carson, Valerie; Chaput, Jean-Philippe; Janssen, Ian; Tremblay, Mark S

2017-10-18

The Canadian 24-Hour Movement Guidelines for Children and Youth: An Integration of Physical Activity, Sedentary Behaviour, and Sleep , provide specific recommendations on the amount of time over a typical 24-hour day that children and youth aged 5 to 17 should spend in moderate-to-vigorous physical activity (at least 60 minutes), recreational screen time (no more than 2 hours), and sleep (9 to 11 hours for 5- to 13-year-olds; 8 to 10 hours for 14- to 17-year-olds). Based on combined results of cycles 2 (2009-to-2011) and 3 (2012-to-2013) of the Canadian Health Measures Survey, this analysis examines average daily moderate-to-vigorous physical activity, screen time and sleep duration of 5- to 11-year-olds and 12- to 17-year-olds, and the percentages meeting the 24-Hour Guidelines' recommendations. Findings are presented overall and by age group and sex. Differences in average daily times between groups were tested for statistical significance, as weredifferences between groups in the percentages meeting each recommendation and combination of recommendations. Overall, 17.5% of children and youth met the 24-Hour Guidelines' specific time recommendations. Higher percentages of children than youth (29.6% versus 5.5%) and boys than girls (22.9% versus 11.8%) met the recommendations. About a third (36.3%) met two of the three recommendations. Recommendations for moderate-to-vigorous physical activity, sedentary behaviour, and sleep have higher levels of adherence among children than youth.

Fixed-dose combination therapy for the prevention of cardiovascular disease

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de Cates, Angharad N; Farr, Matthew RB; Rees, Karen; Casas, Juan P; Huffman, Mark

2014-01-01

This is the protocol for a review and there is no abstract. The objectives are as follows: To determine the effectiveness of fixed-dose combination therapy on optimising CVD risk factors and reducing CVD fatal and non-fatal events for both primary and secondary prevention of CVD. Details of CVD events and risk factors included are listed in the methods. We will also determine any adverse events associated with taking fixed-dose combination therapy. This will include studies conducted in both developed and developing regions of the world. PMID:25267903

29 CFR 785.22 - Duty of 24 hours or more.

Science.gov (United States)

2010-07-01

... employee is required to be on duty for 24 hours or more, the employer and the employee may agree to exclude... from hours worked, provided adequate sleeping facilities are furnished by the employer and the employee... of sleeping time and lunch periods constitute hours worked. (Armour v. Wantock, 323 U.S. 126 (1944...

Pharmacokinetic/pharmacodynamic modeling for the determination of a cimicoxib dosing regimen in the dog.

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Jeunesse, Elisabeth C; Schneider, Marc; Woehrle, Frederique; Faucher, Mathieu; Lefebvre, Herve P; Toutain, Pierre-Louis

2013-12-11

Cimicoxib is a new coxib anti-inflammatory drug for use in the dog. To determine a preclinical dosage regimen for cimicoxib in dog, a reversible model of kaolin-induced paw inflammation was used. Dosage regimens were established using pharmacokinetic/pharmacodynamic (PK/PD) modeling approach (indirect response model). Analgesic, anti-inflammatory and antipyretic endpoints investigated with the inflammation model established the efficacy of cimicoxib at a dose of 2 mg/kg administered orally (single dose) in 12 beagle dogs.For both the oral and IV route of administration two groups of dogs to be identified namely Poor Metabolizers (PM) and Extensive Metabolizers (EM).The terminal half-life after oral administration was 8.0 ± 0.6 h for the PM and 4.6 ± 2.6 h for the EM groups, with the corresponding values after the IV route being 5.6 ± 1.7 h and 2.7 ± 0.9 h (mean ± SD).The main pharmacodynamic parameters (potency, efficacy, and sensitivity) were estimated for four endpoints (body temperature, creeping speed, ground vertical reaction force and clinical lameness score). The plasma concentration corresponding to half the maximum of the indirect effect were 239 μg/L for creeping speed, 284 μg/L for the lameness score, 161 μg/L for the ground reaction vertical force and 193 μg/L for the body temperature.To document possible polymorphism of the cimicoxib disposition in the target dog population, cimicoxib was administered by the intravenous route to 40 dogs (four different sized breeds). The cimicoxib half-lives in these 40 dogs were of same order of the magnitude as those of the EM beagle dogs. Thus pharmacokinetic and pharmacodynamic parameters obtained from the EM beagle dogs were selected to simulate the dose-effect relationship of cimicoxib after an oral administration allowing a dosage regimen to be selected for confirmation by a clinical trial. Cimicoxib was an efficacious anti-inflammatory, antipyretic and analgesic drug and a dosage regimen of 2 mg

Hourly awakening vs continuous contact lens sensor measurements of 24-hour intraocular pressure: effect on sleep macrostructure and intraocular pressure rhythm.

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Aptel, Florent; Tamisier, Renaud; Pépin, Jean-Louis; Mottet, Benjamin; Hubanova, Ralitsa; Romanet, Jean-Paul; Chiquet, Christophe

2014-10-01

All studies of 24-hour intraocular pressure (IOP) rhythm conducted to date have used repeated IOP measurements requiring nocturnal awakenings, potentially disturbing sleep macrostructure. To evaluate the effects on sleep architecture and IOP rhythm of hourly awakening vs a contact lens sensor (CLS) to continuously monitor IOP without awakening. Cross-sectional study at a referral center of chronobiology among 12 young healthy volunteers, with a mean (SD) age of 22.3 (2.3) years. Volunteers underwent two 24-hour IOP measurement sessions during a 2-month period. The eye order and session order were randomized. During one session, the IOP of the first eye was continuously monitored using a CLS, and the IOP of the fellow eye was measured hourly using a portable noncontact tonometer (session with nocturnal hourly awakening). During the other session, the IOP of the first eye was continuously monitored using a CLS, and the IOP of the fellow eye was not measured (session without nocturnal awakening). Overnight polysomnography was performed during the 2 sessions. A nonlinear least squares, dual-harmonic regression analysis was used to model the 24-hour IOP rhythm from the CLS data. Comparisons of acrophase, bathyphase, amplitude, and the midline estimating statistic of rhythm were used to evaluate the effect of hourly awakening on IOP rhythm. To evaluate the effects of hourly awakening on sleep architecture, comparisons of sleep structure were used, including total sleep period, rapid eye movement, wake after sleep onset, absolute and relative total sleep time, and non-rapid eye movement sleep (N1, N2, and N3). A 24-hour IOP rhythm was found in all individuals for the sessions with and without awakening (P  .30). Hourly awakening during noncontact tonometer IOP measurements did not seem to alter the mean variables of the 24-hour IOP pattern evaluated using CLS, including signal, maximum signal, minimum signal, acrophase, and bathyphase (P > .15). The 24-hour IOP

Java programming 24-hour trainer

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Fain, Yakov

2015-01-01

Quick and painless Java programming with expert multimedia instruction Java Programming 24-Hour Trainer, 2nd Edition is your complete beginner's guide to the Java programming language, with easy-to-follow lessons and supplemental exercises that help you get up and running quickly. Step-by-step instruction walks you through the basics of object-oriented programming, syntax, interfaces, and more, before building upon your skills to develop games, web apps, networks, and automations. This second edition has been updated to align with Java SE 8 and Java EE 7, and includes new information on GUI b

WordPress 24-hour trainer

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Plumley, George

2015-01-01

Create and expand feature-rich sites with no programming experience Ready to build, maintain, and expand your web site with WordPress but have no prior programming experience? WordPress 24-Hour Trainer, 3rd Edition is your book-and-video learning solution that walks you step-by-step through all the important features you will need to know. Lessons range from focused, practical everyday tasks to more advanced, creative features. Learn from an industry professional how to enter content, create pages, manage menus, utilize plug-ins, connect to social media, create membership and e-commerce site

Association between number of doses per day, number of medications and patient's non-compliance, and frequency of readmissions in a multi-ethnic Asian population

Directory of Open Access Journals (Sweden)

Ming Ren Toh

2014-01-01

Conclusion: Complex medication regimen (i.e. multiple medications and multiple doses per day is a statistically significant predictor of number of readmissions. Simplifying therapeutic regimens with alternatives such as longer-acting or fixed-dose combination drugs may facilitate better patient adherence and reduce costly readmissions.

Use of an integrated modelling and simulation approach to develop a simplified peginterferon alfa-2a dosing regimen for children with hepatitis C.

Science.gov (United States)

Brennan, Barbara J; Lemenuel-Diot, Annabelle; Snoeck, Eric; McKenna, Michael; Solsky, Jonathan; Wat, Cynthia; Mallalieu, Navita L

2016-04-01

The aim of the study was to simplify the dosing regimen of peginterferon alfa-2a in paediatric patients with chronic hepatitis C. A population pharmacokinetic (PK) model was developed using PK data from 14 children aged 2-8 years and 402 adults. Simulations were produced to identify a simplified dosing regimen that would provide exposures similar to those observed in the paediatric clinical trials and in the range known to be safe/efficacious in adults. Model predictions were evaluated against observed adult and paediatric data to reinforce confidence of the proposed dosing regimen. The final model was a two compartment model with a zero order resorption process. Covariates included a linear influence of body surface area (BSA) on apparent oral clearance (CL/F) and a linear influence of body weight on apparent volume of distribution of the central compartment (V1 /F). A simplified dosing regimen was developed which is expected to provide exposures in children aged ≥5 years similar to the dosing formula used in the paediatric clinical trial and within the range that is safe/efficacious in adults. This simplified regimen is approved in the EU and in other countries for the treatment of chronic hepatitis C in treatment-naive children/adolescents aged ≥5 years in combination with ribavirin. Pre-existing adult PK data were combined with relatively limited paediatric PK data to develop a PK model able to predict exposure in both populations adequately. This provided increased confidence in characterizing PK in children and helped in the development of a simplified dosing regimen of peginterferon alfa-2a in paediatric patients. © 2015 The British Pharmacological Society.

Ocular pharmacokinetics and tolerability of bimatoprost ophthalmic solutions administered once or twice daily in rabbits, and clinical dosing implications

Science.gov (United States)

Shen, Jie; Goodkin, Margot L; Tong, Warren; Attar, Mayssa

2017-01-01

Purpose Fixed-combination medications can benefit patients requiring multiple agents to lower their intraocular pressure (IOP), but combining agents with complementary mechanisms of action is challenging if their dosing frequency differs. This study compares in vivo pharmacokinetic and ocular tolerability of bimatoprost 0.01% ophthalmic solutions dosed once or twice daily. Reports of twice-daily dosing in glaucoma patients are also reviewed. Methods New Zealand White rabbits were administered bimatoprost 0.01% monotherapy or fixed-combination bimatoprost 0.01%/brimonidine 0.1%, once or twice daily in both eyes for 4 days. Ocular tissues were harvested and analyzed by liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters calculated included maximum observed concentration, time to maximum concentration, and area under the concentration-time curve. Results Due to extensive metabolism, bimatoprost concentration was below the quantitation limit by 1 hour post-dose in all samples. Bimatoprost acid exposure, however, could be measured up to 6–8 hours post-dose and was similar in the aqueous humor and iris-ciliary body (pharmacological site of action) of animals treated once or twice daily with either bimatoprost 0.01% or fixed-combination bimatoprost 0.01%/brimonidine 0.1%. Increasing dosage frequency in rabbits did not raise the incidence of drug-related conjunctival hyperemia (most common adverse event associated with bimatoprost use in humans), suggesting comparable ocular tolerability of the once- and twice-daily regimens for each formulation. Conclusion Bimatoprost 0.01% administered once or twice daily as monotherapy and in fixed-combination with brimonidine 0.1% in rabbits show similar pharmacokinetic profiles of bimatoprost acid, especially in the iris-ciliary body. Key findings from previous clinical studies suggest that by varying the concentration of benzalkonium chloride (a preservative with corneal penetration-enhancing properties

Deconvolution analysis of 24-h serum cortisol profiles informs the amount and distribution of hydrocortisone replacement therapy.

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Peters, Catherine J; Hill, Nathan; Dattani, Mehul T; Charmandari, Evangelia; Matthews, David R; Hindmarsh, Peter C

2013-03-01

Hydrocortisone therapy is based on a dosing regimen derived from estimates of cortisol secretion, but little is known of how the dose should be distributed throughout the 24 h. We have used deconvolution analysis of 24-h serum cortisol profiles to determine 24-h cortisol secretion and distribution to inform hydrocortisone dosing schedules in young children and older adults. Twenty four hour serum cortisol profiles from 80 adults (41 men, aged 60-74 years) and 29 children (24 boys, aged 5-9 years) were subject to deconvolution analysis using an 80-min half-life to ascertain total cortisol secretion and distribution throughout the 24-h period. Mean daily cortisol secretion was similar between adults (6.3 mg/m(2) body surface area/day, range 5.1-9.3) and children (8.0 mg/m(2) body surface area/day, range 5.3-12.0). Peak serum cortisol concentration was higher in children compared with adults, whereas nadir serum cortisol concentrations were similar. Timing of the peak serum cortisol concentration was similar (07.05-07.25), whereas that of the nadir concentration occurred later in adults (midnight) compared with children (22.48) (P = 0.003). Children had the highest percentage of cortisol secretion between 06.00 and 12.00 (38.4%), whereas in adults this took place between midnight and 06.00 (45.2%). These observations suggest that the daily hydrocortisone replacement dose should be equivalent on average to 6.3 mg/m(2) body surface area/day in adults and 8.0 mg/m(2) body surface area/day in children. Differences in distribution of the total daily dose between older adults and young children need to be taken into account when using a three or four times per day dosing regimen. © 2012 Blackwell Publishing Ltd.

Evaluation of radioiodine therapy with fixed doses of 10 and 15 mCi in patients with Graves disease

International Nuclear Information System (INIS)

Canadas, Viviane; Vilar, Lucio; Moura, Eliane; Brito, Ana; Castellar, Enio

2007-01-01

The treatment options for the hyperthyroidism of Graves' disease are antithyroid drugs, surgery and radioiodine, none of which is considered ideal, as they do not act directly on the etiopathogenesis of the disease. Radioiodine has been increasingly used as the treatment of choice because it is a safe and definitive therapy whose administration is very easy. Some authors prefer to administer higher doses in order to deliberately induce hypothyroidism, while others recommend lower doses that result in a lower incidence of hypothyroidism and a greater incidence of euthyroidism. There is no consensus for the optimal regimen of fixed doses to be used and this is the main focus of the present study, where doses of 10 and 15 mCi of 131 I were compared. Among the 164 patients analyzed, 61 (37.2%) were submitted to 10 mCi and 103 (62.8%) to 15 mCi. In the longitudinal analysis it was observed that remission of the hyperthyroidism was statistically different in the sixth month (p 131 I brought about a similar remission of the hyperthyroidism after 12 months of treatment. Moreover, the remission rate of the hyperthyroidism had no association with age, sex or previous therapy with antithyroid drugs. (author)

Pharmacokinetic/pharmacodynamic based dosing of ciprofloxacin in complicated urinary tract infections

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Ana Sabo

2015-08-01

Full Text Available Ciprofloxacin is often used in treatment of complicated urinary tract infections in areas with high rates of resistance to first line agents. The aim of this study was to evaluate efficacy of ciprofloxacin in standard dosing regimens in treatment of complicated urinary tract infections. Plasma concentration curves were simulated and minimum inhibitory concentration (MIC and post-antibiotic effect were determined. Ciprofloxacin MIC ranged from 0.0156 for Gram-negative and to 0.125-0.5 µg/mL for Gram-positive bacteria. Both dosing regimens were suitable for eradication of Gram-negative bacteria, with slight supremacy of 750 mg/12 hours over 500 mg/12 hours dosing regimen. Even though all strains were fully susceptible to ciprofloxacin, pharmaco-kinetic/pharmacodynamic parameters did not meet target thresholds for pathogens with MIC over 0.1-0.2 µg/mL regardless of the administered dose. Ciprofloxacin remains an excellent choice for treatment of complicated urinary tract infections caused by Gram-negative bacteria, but in infection caused by Gram-positive strains, deeper analysis is necessary in order to achieve optimal results.

Safety and efficacy of fixed-dose 10 mg daily isotretinoin treatment for acne vulgaris in Malaysia.

Science.gov (United States)

Yap, Felix Boon-Bin

2017-09-01

Low-dose isotretinoin is used to reduce side effects albeit higher relapse. This study aimed to determine the efficacy and safety of fixed-dose 10 mg daily isotretinoin for the treatment of acne. This prospective study was performed between 2011 and 2015. All 150 patients were given 10 mg daily isotretinoin until a cumulative dose of 90-110 mg/kg. The mean age was 26.6 years with 64.7% moderate acne, 29.3% severe, and 6% very severe. The mean cumulative dose was 98.8 ± 6.05 mg/kg. All 150 patients had total clearance with a mean time to clearance of 24.0 weeks. Patients with severe/very severe acne had higher cumulative dosage (102.1 vs. 97.0, P < 0.001) and longer duration to clearance (32.9 weeks vs. 19.1 weeks, P < 0.001). Mild relapse was seen in 4%. The mean time to relapse was 32.3 weeks. Lip dryness was the commonest side effects (100%). Mild transient elevation of liver enzymes was detected in 3.3% and a slight increase of serum lipid in 2.7% with no treatment discontinuation. Fixed-dose 10 mg daily treatment with isotretinoin until a cumulative dose of 90-110 mg/kg is safe with low relapse rate. © 2016 Wiley Periodicals, Inc.

Optimal Clinical Doses of Faropenem, Linezolid, and Moxifloxacin in Children With Disseminated Tuberculosis: Goldilocks.

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Srivastava, Shashikant; Deshpande, Devyani; Pasipanodya, Jotam; Nuermberger, Eric; Swaminathan, Soumya; Gumbo, Tawanda

2016-11-01

 When treated with the same antibiotic dose, children achieve different 0- to 24-hour area under the concentration-time curves (AUC 0-24 ) because of maturation and between-child physiological variability on drug clearance. Children are also infected by Mycobacterium tuberculosis isolates with different antibiotic minimum inhibitory concentrations (MICs). Thus, each child will achieve different AUC 0-24 /MIC ratios when treated with the same dose.  We used 10 000-subject Monte Carlo experiments to identify the oral doses of linezolid, moxifloxacin, and faropenem that would achieve optimal target exposures associated with optimal efficacy in children with disseminated tuberculosis. The linezolid and moxifloxacin exposure targets were AUC 0-24 /MIC ratios of 62 and 122, and a faropenem percentage of time above MIC >60%, in combination therapy. A linezolid AUC 0-24 of 93.4 mg × hour/L was target for toxicity. Population pharmacokinetic parameters of each drug and between-child variability, as well as MIC distribution, were used, and the cumulative fraction of response (CFR) was calculated. We also considered drug penetration indices into meninges, bone, and peritoneum.  The linezolid dose of 15 mg/kg in full-term neonates and infants aged up to 3 months and 10 mg/kg in toddlers, administered once daily, achieved CFR ≥ 90%, with linezolid AUC 0-24 associated with toxicity. The moxifloxacin dose of 25 mg/kg/day achieved a CFR > 90% in infants, but the optimal dose was 20 mg/kg/day in older children. The faropenem medoxomil optimal dosage was 30 mg/kg 3-4 times daily.  The regimen and doses of linezolid, moxifloxacin, and faropenem identified are proposed to be adequate for all disseminated tuberculosis syndromes, whether drug-resistant or -susceptible. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

Effectiveness and tolerance of long-term malaria prophylaxis with mefloquine. Need for a better dosing regimen.

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Lobel, H O; Bernard, K W; Williams, S L; Hightower, A W; Patchen, L C; Campbell, C C

1991-01-16

To measure the effectiveness and tolerance of long-term malaria prophylaxis with mefloquine, the incidence of Plasmodium falciparum malaria and of adverse reactions was compared in Peace Corps volunteers in West Africa who took mefloquine every 2 weeks and in volunteers who took chloroquine phosphate weekly. Mefloquine was only 63% more effective than chloroquine; the monthly incidence of P falciparum infections was one case per 100 volunteers who took mefloquine and 2.7 cases per 100 volunteers who took chloroquine. Using daily proguanil (chloroguanide) hydrochloride in addition to chloroquine did not provide additional protection. All mefloquine prophylaxis failures occurred during the second week of the every-2-weeks dosing regimen in volunteers who had used mefloquine for more than 2 months. Blood concentrations of mefloquine were lower during the second week of the alternate-week regimen than during the first week, suggesting that blood levels are too low during the second week to suppress parasitemia. No serious adverse reactions were observed. The results indicate that a dosing regimen of 250 mg of mefloquine weekly should be considered for travelers to areas with chloroquine-resistant P falciparum malaria.

Effects of para-aminobenzoic acid (PABA) form and administration mode on PABA recovery in 24-hour urine collections.

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Sharma, Rashmi S; Joy, Raechel C; Boushey, Carol J; Ferruzzi, Mario G; Leonov, Alexei P; McCrory, Megan A

2014-03-01

Para-aminobenzoic acid (PABA) has long been used as an objective measure to assess completeness of 24-hour urine collections. However, pharmaceutical-grade PABA for human ingestion is not available in the United States. An alternative, the potassium salt of PABA, aminobenzoate potassium, can be obtained for clinical use, although it has not yet been validated in this role. Both PABA and aminobenzoate potassium can be directly ingested in their tablet or capsule forms or added to food before consumption. Our aim was to investigate the effect of form (PABA vs aminobenzoate potassium) and administration mode (directly ingested as a tablet/capsule vs added to food) on urinary PABA recovery levels. Twenty healthy participants underwent 3 test days separated by two 24-hour wash-out periods. Three test conditions, one on each test day, were investigated in randomized order: PABA tablet, aminobenzoate potassium capsule, and PABA or aminobenzoate potassium in food. Ingestion of each dose was supervised and participants performed the 24-hour urine collections while free-living. The 24-hour urine collections were analyzed for PABA recovery (%R) levels using a colorimetric assay. Recoveries 85% to 110% were deemed complete and those >110% were reanalyzed by high pressure liquid chromatography and mass spectrometry. Only complete collections (>85%R) were included in analyses. The recovery for the PABA tablet, aminobenzoate potassium capsule, and PABA/aminobenzoate potassium in food were similar at 98.8%R±2.0%R, 95.1%R±2.3%R, and 93.2%R±2.1%R, respectively, and did not differ significantly. These results suggest that aminobenzoate potassium may be used as an alternative to PABA for assessing the completeness of 24-hour urine collections and to track compliance with consuming provided diets in community-dwelling studies. Copyright © 2014 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

The effect of dosing regimen on the pharmacokinetics of risedronate

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Mitchell, David Y; Heise, Mark A; Pallone, Karen A; Clay, Marian E; Nesbitt, John D; Russell, Darrell A; Melson, Chad W

1999-01-01

Aims To examine the effect of timing of a risedronate dose relative to food intake on the rate and extent of risedronate absorption following single-dose, oral administration to healthy male and female volunteers. Methods A single-dose, randomized, parallel study design was conducted with volunteers assigned to four treatment groups (31 or 32 subjects per group, 127 subjects total). Each subject was orally administered 30 mg risedronate. Group 1 was fasted for 10 h prior to and 4 h after dosing (fasted group); Groups 2 and 3 were fasted for 10 h and were dosed 1 and 0.5 h, respectively, before a high-fat breakfast; and Group 4 was dosed 2 h after a standard dinner. Blood and urine samples were collected for 168 h after dosing. Pharmacokinetic parameters were estimated by simultaneous analysis of risedronate serum concentration and urinary excretion rate-time data. Results Extent of risedronate absorption (AUC and Ae) was comparable (P = 0.4) in subjects dosed 2 h after dinner and 0.5 h before breakfast; however, a significantly greater extent of absorption occurred when risedronate was given 1 or 4 h prior to a meal (1.4- to 2.3-fold greater). Administration 0.5, 1, or 4 h prior to a meal resulted in a significantly greater rate of absorption (Cmax 2.8-, 3.5-, and 4.1-fold greater, respectively) when compared with 2 h after dinner. Conclusions The comparable extent of risedronate absorption when administered either 0.5–1 h before breakfast or 2 h after an evening meal support previous clinical studies where risedronate was found to have similar effectiveness using these dosing regimens. This flexibility in the timing of risedronate administration may provide patients an alternative means to achieve the desired efficacy while maintaining their normal daily routine. PMID:10583024

Assessment of radioactivity for 24 hours urine sample depending on correction factor by using creatinine

International Nuclear Information System (INIS)

Kharita, M. H.; Maghrabi, M.

2006-09-01

Assessment of intake and internal does requires knowing the amount of radioactivity in 24 hours urine sample, sometimes it is difficult to get 24 hour sample because this method is not comfortable and in most cases the workers refuse to collect this amount of urine. This work focuses on finding correction factor of 24 hour sample depending on knowing the amount of creatinine in the sample whatever the size of this sample. Then the 24 hours excretion of radionuclide is calculated assuming the average creatinine excretion rate is 1.7 g per 24 hours, based on the amount of activity and creatinine in the urine sample. Several urine sample were collected from occupationally exposed workers the amount and ratios of creatinine and activity in these samples were determined, then normalized to 24 excretion of radionuclide. The average chemical recovery was 77%. It should be emphasized that this method should only be used if a 24 hours sample was not possible to collect. (author)

Fixed dose 131-I treatment in Basedow patients

International Nuclear Information System (INIS)

Klisarova, A; Bochev, P.; Hristosov, K.

2003-01-01

The choice of a treatment for Basedow patients is still unsolved problem. The treatment with 131-I has certain advantages but the determination of the individual therapeutic dose is impossible. The aim of the study is to assess the efficiency of the treatment with a fixed dose. 23 patient have been treated, 30 women and 3 men, age between 48 and 78. All patients are with chronic disease with relapses (1 to 4 relapses). 5 of the patients are with a thyrotoxic heart, 3 - with ophtalmopatia, 2 - with toxic medicamentous hepatitis and 2 with allergies to thyreostatics. Before the treatment with 131-I all patients have been in euthyroid state with normal levels of the peripheral hormones. All patients have received initial doses of 5 mCi 131-I. The hormone levels have been followed on 3rd, 6th, 12th and 24th month after the uptake. From a total of 23 patients, in 3 cases a transitional hypothyroidism has been found between 3th and 6th month, in 3 patients - permanent hypothyroidism. In 5 patients after the 6th month an additional dose of 5 mCi 131-I is given (in one woman a permanent hypothyroidism is reached). Four of the patients have been with a significant thyroid hyperplasia with volume above 60 ml. In three patients in the period between 6th and 12th month a slight hyperthyroidism is registered, which have been suppressed by a low dose thyreostatic. A year after the treatment they have been found euthyroid. The decision for giving a second dose have been based on the evident heptahydrate symptomatic s and the persisting increased thyroid volume. In one case it is observed an acute thyrotoxicosis for 3-5 days after the 131 I uptake. No cases of worsening of the eye symptoms are observed. In conclusion, the treatment with 131 I is a appropriate method for patients with cardiovascular complications, contraindication for surgery or side effects of the thyreostatic treatment. the dose od 5 mCi is sufficient for patients with mild to medium form of Basedow disease and a

Terbinafine in combination with other antifungal agents for treatment of resistant or refractory mycoses: investigating optimal dosing regimens using a physiologically based pharmacokinetic model.

Science.gov (United States)

Dolton, Michael J; Perera, Vidya; Pont, Lisa G; McLachlan, Andrew J

2014-01-01

Terbinafine is increasingly used in combination with other antifungal agents to treat resistant or refractory mycoses due to synergistic in vitro antifungal activity; high doses are commonly used, but limited data are available on systemic exposure, and no assessment of pharmacodynamic target attainment has been made. Using a physiologically based pharmacokinetic (PBPK) model for terbinafine, this study aimed to predict total and unbound terbinafine concentrations in plasma with a range of high-dose regimens and also calculate predicted pharmacodynamic parameters for terbinafine. Predicted terbinafine concentrations accumulated significantly during the first 28 days of treatment; the area under the concentration-time curve (AUC)/MIC ratios and AUC for the free, unbound fraction (fAUC)/MIC ratios increased by 54 to 62% on day 7 of treatment and by 80 to 92% on day 28 compared to day 1, depending on the dose regimen. Of the high-dose regimens investigated, 500 mg of terbinafine taken every 12 h provided the highest systemic exposure; on day 7 of treatment, the predicted AUC, maximum concentration (Cmax), and minimum concentration (Cmin) were approximately 4-fold, 1.9-fold, and 4.4-fold higher than with a standard-dose regimen of 250 mg once daily. Close agreement was seen between the concentrations predicted by the PBPK model and the observed concentrations, indicating good predictive performance. This study provides the first report of predicted terbinafine exposure in plasma with a range of high-dose regimens.

Dose Response for Radiation Cataractogenesis: A Meta-Regression of Hematopoietic Stem Cell Transplantation Regimens

International Nuclear Information System (INIS)

Hall, Matthew D.; Schultheiss, Timothy E.; Smith, David D.; Nguyen, Khanh H.; Wong, Jeffrey Y.C.

2015-01-01

Purpose/Objective(s): To perform a meta-regression on published data and to model the 5-year probability of cataract development after hematopoietic stem cell transplantation (HSCT) with and without total body irradiation (TBI). Methods and Materials: Eligible studies reporting cataract incidence after HSCT with TBI were identified by a PubMed search. Seventeen publications provided complete information on radiation dose schedule, fractionation, dose rate, and actuarial cataract incidence. Chemotherapy-only regimens were included as zero radiation dose regimens. Multivariate meta-regression with a weighted generalized linear model was used to model the 5-year cataract incidence and contributory factors. Results: Data from 1386 patients in 21 series were included for analysis. TBI was administered to a total dose of 0 to 15.75 Gy with single or fractionated schedules with a dose rate of 0.04 to 0.16 Gy/min. Factors significantly associated with 5-year cataract incidence were dose, dose times dose per fraction (D•dpf), pediatric versus adult status, and the absence of an ophthalmologist as an author. Dose rate, graft versus host disease, steroid use, hyperfractionation, and number of fractions were not significant. Five-fold internal cross-validation showed a model validity of 83% ± 8%. Regression diagnostics showed no evidence of lack-of-fit and no patterns in the studentized residuals. The α/β ratio from the linear quadratic model, estimated as the ratio of the coefficients for dose and D•dpf, was 0.76 Gy (95% confidence interval [CI], 0.05-1.55). The odds ratio for pediatric patients was 2.8 (95% CI, 1.7-4.6) relative to adults. Conclusions: Dose, D•dpf, pediatric status, and regimented follow-up care by an ophthalmologist were predictive of 5-year cataract incidence after HSCT. The low α/β ratio indicates the importance of fractionation in reducing cataracts. Dose rate effects have been observed in single institution studies but not in the

Dose Response for Radiation Cataractogenesis: A Meta-Regression of Hematopoietic Stem Cell Transplantation Regimens

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Hall, Matthew D. [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Schultheiss, Timothy E., E-mail: schultheiss@coh.org [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Smith, David D. [Division of Biostatistics, City of Hope National Medical Center, Duarte, California (United States); Nguyen, Khanh H. [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Department of Radiation Oncology, Bayhealth Cancer Center, Dover, Delaware (United States); Wong, Jeffrey Y.C. [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States)

2015-01-01

Purpose/Objective(s): To perform a meta-regression on published data and to model the 5-year probability of cataract development after hematopoietic stem cell transplantation (HSCT) with and without total body irradiation (TBI). Methods and Materials: Eligible studies reporting cataract incidence after HSCT with TBI were identified by a PubMed search. Seventeen publications provided complete information on radiation dose schedule, fractionation, dose rate, and actuarial cataract incidence. Chemotherapy-only regimens were included as zero radiation dose regimens. Multivariate meta-regression with a weighted generalized linear model was used to model the 5-year cataract incidence and contributory factors. Results: Data from 1386 patients in 21 series were included for analysis. TBI was administered to a total dose of 0 to 15.75 Gy with single or fractionated schedules with a dose rate of 0.04 to 0.16 Gy/min. Factors significantly associated with 5-year cataract incidence were dose, dose times dose per fraction (D•dpf), pediatric versus adult status, and the absence of an ophthalmologist as an author. Dose rate, graft versus host disease, steroid use, hyperfractionation, and number of fractions were not significant. Five-fold internal cross-validation showed a model validity of 83% ± 8%. Regression diagnostics showed no evidence of lack-of-fit and no patterns in the studentized residuals. The α/β ratio from the linear quadratic model, estimated as the ratio of the coefficients for dose and D•dpf, was 0.76 Gy (95% confidence interval [CI], 0.05-1.55). The odds ratio for pediatric patients was 2.8 (95% CI, 1.7-4.6) relative to adults. Conclusions: Dose, D•dpf, pediatric status, and regimented follow-up care by an ophthalmologist were predictive of 5-year cataract incidence after HSCT. The low α/β ratio indicates the importance of fractionation in reducing cataracts. Dose rate effects have been observed in single institution studies but not in the

ASA24 enables multiple automatically coded self-administered 24-hour recalls and food records

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A freely available web-based tool for epidemiologic, interventional, behavioral, or clinical research from NCI that enables multiple automatically coded self-administered 24-hour recalls and food records.

Neutron doses to personnel from a 24 MeV betatron

International Nuclear Information System (INIS)

Beckham, W.A; Entwistle, R.F.

1987-01-01

Neutrons are produced by bombardment of most materials by high-energy photons. Because the x-ray shielding around high-energy x-ray generators may not have been designed with neutrons in mind there may be unexpected contributions to the radiation doses of staff working in the immediate vicinity. Neutron fluxes in the working area close to an Allis-Chalmers 24 MeV betatron have been measured using a lithium-6-loaded scintillator and the dose rates calculated. Hazard of staff has been found to be low; typical dose-equivalent rates in occupied areas range from 0.0042 to 0.012 mrem/hour. The flux of fast neutrons in the treatment room was found to be essentially zero. Measurements of neutron flux may be routinely performed using the scintillation detector (NE 912) described, and could usefully form part of the acceptance protocol for any new accelerator

Assessment of serum magnesium levels and its outcome in neonates of eclamptic mothers treated with low-dose magnesium sulfate regimen

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Das, Monalisa; Chaudhuri, Patralekha Ray; Mondal, Badal C.; Mitra, Sukumar; Bandyopadhyay, Debasmita; Pramanik, Sushobhan

2015-01-01

Objectives: Magnesium historically has been used for treatment and/or prevention of eclampsia. Considering the low body mass index of Indian women, a low-dose magnesium sulfate regime has been introduced by some authors. Increased blood levels of magnesium in neonates is associated with increased still birth, early neonatal death, birth asphyxia, bradycardia, hypotonia, gastrointestinal hypomotility. The objective of this study was to assess safety of low-dose magnesium sulfate regimen in neonates of eclamptic mothers treated with this regimen. Materials and Methods: This was a cross-sectional observational study of 100 eclampsia patients and their neonates. Loading dose and maintenance doses of magnesium sulfate were administered to patients by combination of intravenous and intramuscular routes. Maternal serum and cord blood magnesium levels were estimated. Neonatal outcome was assessed. Results: Bradycardia was observed in 18 (19.15%) of the neonates, 16 (17.02%) of the neonates were diagnosed with hypotonia. Pearson Correlation Coefficient showed Apgar scores decreased with increase in cord blood magnesium levels. Unpaired t-test showed lower Apgar scores with increasing dose of magnesium sulfate. The Chi-square/Fisher's exact test showed significant increase in hypotonia, birth asphyxia, intubation in delivery room, Neonatal Intensive Care Unit (NICU) care requirement, with increasing dose of magnesium sulfate. (P ≤ 0.05). Conclusion: Several neonatal complications are significantly related to increasing serum magnesium levels. Overall, the low-dose magnesium sulfate regimen was safe in the management of eclamptic mothers, without toxicity to their neonates. PMID:26600638

High-dose metoclopramide + lorazepam versus low-dose metoclopramide + lorazepam + dehydrobenzperidol in the treatment of cisplatin-induced nausea and vomiting

DEFF Research Database (Denmark)

Herrstedt, Jørn; Hannibal, J; Hallas, Jesper

1991-01-01

In a randomized double-blind, cross-over trial of 34 patients receiving cisplatin-based chemotherapy (20-100 mg/m2), the antiemetic effect of high-dose metoclopramide (HDM) (10 mg/kg iv. loading dose + 7 hours continuous infusion) + lorazepam (L) (2.5 mg x 4 po) was compared with low......-dose metoclopramide (LDM) (70 mg) + L (2.5 mg x 2 po) + dehydrobenzperidol (5 mg x 2 im). Among the 29 patients who completed the cross-over, HDM significantly reduced the number of vomiting episodes (p = 0.002) and the degree of nausea (p = 0.004). Seventeen patients preferred the HDM and 4 the LDM regimen (p = 0.......01). Sedation was seen in all but 1 patient, and was graded as severe in 6 patients receiving the HDM and in 2 patients receiving the LDM regimen. No extrapyramidal adverse reactions were seen. We conclude that high-dose metoclopramide + lorazepam is a safe antiemetic regimen and significantly superior to low...

Preclinical Evaluations To Identify Optimal Linezolid Regimens for Tuberculosis Therapy

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Drusano, George L.; Adams, Jonathan R.; Rodriquez, Jaime L.; Jambunathan, Kalyani; Baluya, Dodge L.; Brown, David L.; Kwara, Awewura; Mirsalis, Jon C.; Hafner, Richard; Louie, Arnold

2015-01-01

ABSTRACT Linezolid is an oxazolidinone with potent activity against Mycobacterium tuberculosis. Linezolid toxicity in patients correlates with the dose and duration of therapy. These toxicities are attributable to the inhibition of mitochondrial protein synthesis. Clinically relevant linezolid regimens were simulated in the in vitro hollow-fiber infection model (HFIM) system to identify the linezolid therapies that minimize toxicity, maximize antibacterial activity, and prevent drug resistance. Linezolid inhibited mitochondrial proteins in an exposure-dependent manner, with toxicity being driven by trough concentrations. Once-daily linezolid killed M. tuberculosis in an exposure-dependent manner. Further, 300 mg linezolid given every 12 hours generated more bacterial kill but more toxicity than 600 mg linezolid given once daily. None of the regimens prevented linezolid resistance. These findings show that with linezolid monotherapy, a clear tradeoff exists between antibacterial activity and toxicity. By identifying the pharmacokinetic parameters linked with toxicity and antibacterial activity, these data can provide guidance for clinical trials evaluating linezolid in multidrug antituberculosis regimens. PMID:26530386

Maximal safe dose therapy of I-131 after failure of standard fixed dose therapy in patients with differentiated thyroid carcinoma

International Nuclear Information System (INIS)

Lee, Jong Jin; Seok, Ju Won; Uh, Jae Sun

2005-01-01

In patients with recurrent or metastatic differentiated thyroid carcinoma, residual disease despite repetitive fixed dose I-131 therapy presents an awkward situation in terms of treatment decision making. Maximal safe dose (MSD) administration base on bone marrow radiation allows the delivery of a large amount I-131 to thyroid cancer tissue within the safety margin. We investigated the efficacy of MSD in differentiated thyroid cancers, which had persisted after conventional fixed dose therapy. Forty-six patients with differentiated thyroid carcinoma who had non-responsible residual disease despite repetitive fixed dose I-131 therapy were enrolled in this study. The postoperative pathology consisted of 43 papillary carcinomas and 3 follicular carcinomas. MSD was calculated according the Memorial Sloan Kettering Cancer Center protocol using blood samples. MSDs were administered at intervals of at least 6 months. Treatment responses were evaluated using I-131 whole body scan (WBS) and serum thyroglobulin measurements. Mean calculated MSD was 12.5±2.1 GBq. Of the 46 patients, 6 (13.0%) showed complete remission, 15 (32.6%) partial response, 19 (41.3%) stable disease, and 6 (13.0%) disease progression. Thus, about a half of the patients showed complete or partial remission, and of these patients, 14 (67%) showed response after a single MSD administration and 6 (29%) showed response after the second dose of MSD administrations. Twenty-nine patients (63%) experienced transient cytopenia after therapy, and recovered spontaneously with the exception of one. MSD administration is an effective method even in the patients who failed to be treated by conventional fixed dose therapy. MSD therapy of I-131 can be considered in the patients who failed by fixed dose therapy

Maximal safe dose of I-131 after failure of standard fixed dose therapy in patients with differentiated thyroid carcinoma

International Nuclear Information System (INIS)

Lee, Jong-Jin; Chung, June-Key; Kim, Sung-Eun; Kang, Won-Jun; Park, Do-Joon; Lee, Dong-Soo; Cho, Bo-Youn; Lee, Myung-Chul

2008-01-01

The maximal safe dose (MSD) on the basis of bone marrow irradiation levels allows the delivery of a large amount of I-131 to thyroid cancer tissue. The efficacy of MSD therapy in differentiated metastatic thyroid cancers that persisted after conventional fixed dose therapy is investigated. Forty-seven differentiated thyroid carcinoma patients with non-responsive residual disease despite repetitive fixed dose I-131 therapy were enrolled in this study. Their postoperative pathologies were 43 papillary carcinomas and 4 follicular carcinomas. The MSD was calculated with the Memorial Sloan-Kettering Cancer Center protocol using serial blood samples. The MSDs were administered at intervals of 6 months. Treatment responses were evaluated using I-131 whole-body scans and serum thyroglobulin measurements. The mean calculated MSD was 12.5±2.1 GBq (339.6±57.5 mCi). Of the 46 patients, 7 (14.9%) showed complete remission, 15 (31.9%) partial remission, 19 (40.4%) stable disease, and 6 (12.8%) disease progression. Of the patients who showed complete or partial remission, 15 (65%) showed response after the first MSD session and 6 (26%) showed response after the second session. Twenty-nine patients (62%) experienced transient cytopenia after therapy, but three did not recover to the baseline level. The maximal safe dose provides an effective means of treatment in patients who failed to respond adequately to conventional fixed dose therapy. I-131 MSD therapy can be considered in patients who fail fixed dose therapy. (author)

Radioiodine (1-131) Dose for the Treatment of Hyperthyroidism in Rajavithi Hospital.

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Kuanrakcharoen, Pichit

2016-02-01

The main cause of hyperthyroidism is diffuse toxic goiter (Graves' disease), and the treatment of choice after medical therapy failure is radioiodine (I-131). There are two common methods of determining the optimal I-131 dose: calculated dose or fixed dose. The calculated dose method is based on the following formula: 75-200 microcuri/gram of thyroid gland divided by the percentage of radioiodine uptake at 24 hours (24-hour RAIU). As this is quite complex, some centers use fixed doses, such as 5, 10 or 15 mCi because it is simpler. At Rajavithi Hospital, the applied dose of I-131 is determined based on the thyroid gland weight assessed by palpation and other clinical factors. To study the mean I-131 dose for the initial treatment of hyperthyroidism in Rajavithi Hospital, to find the clinical factors that correlate with I-131 treatment dose, and to devise a formula to predict the optimal I-131 treatment dose. This was a retrospective study of 510 patients with a diagnosis of hyperthyroidism who received initial I-131 treatment at the Department of Nuclear Medicine in Rajavithi Hospital between January 2014 and June 2015. Baseline characteristics including age, sex, age at diagnosis, duration of antithyroid drug (ATD) therapy, gland weight (g), 3-hour RAIU and I-131 treatment dose were reviewed from medical records. The mean age ± SD was 41.93 ± 14.11 years (range 14-81 years), and the male to female ratio was 4.1:1. The mean duration of ATD therapy was 3.54 ± 4.02 years (min-max, 0.8-40.6 years). The mean gland weight was 54.35 ± 32.95 grams, and the mean 3-hour RAIU was 55.5 ± 23.69%. The mean I-131 treatment dose was 14.84 ± 5.71 mCi (min-max, 7-30 mCi). There was no significant correlation between dose and age, age at diagnosis, duration of A TD therapy or 3-hour RAIU. The study showed a significant correlation between I-131 dose and gland size, r = 0.938 (p treatment of choice for hyperthyroidism after medical therapy failure, and there are various

24-hour aortic blood pressure variability showed a stronger association with carotid damage than 24-hour brachial blood pressure variability: The SAFAR study.

Science.gov (United States)

Yu, Shikai; Chi, Chen; Protogerou, Athanase D; Safar, Michel E; Blacher, Jacques; Argyris, Antonis A; Nasothimiou, Efthimia G; Sfikakis, Petros P; Papaioannou, Theodore G; Xu, Henry; Zhang, Yi; Xu, Yawei

2018-03-01

We aim to compare 24-hour aortic blood pressure variability (BPV) with brachial BPV in relation to carotid damage as estimated by carotid intima-media thickness (CIMT) and cross-sectional area (CCSA). Four hundred and forty five individuals received brachial and aortic 24-hour ambulatory BP monitoring with a validated device (Mobil-O-Graph). Systolic BPV was estimated by average real variability (ARV) and time-weighted standard deviation (wSD). In multiple logistic regression analysis, CIMT > 900 μm was significantly and independently associated with aortic ARV (OR = 1.38; 95% CI: 1.04-1.84), aortic wSD (OR = 1.65; 95% CI: 1.19-2.29) and brachial ARV (OR = 1.53; 95% CI: 1.07-2.18), but not with brachial wSD. CCSA > 90th percentile was significantly and independently associated with aortic ARV (OR = 1.50; 95% CI: 1.07-2.10) and wSD (OR = 1.70; 95% CI: 1.12-2.56), but not with brachial BPVs. In receiver operator characteristics curve analysis, aortic wSD identified CCSA > 90th percentile better than brachial wSD (AUC: 0.73 vs 0.68, P < .01). In conclusion, aortic 24-hour systolic BPV showed a slightly stronger association with carotid damage than brachial BPV. ©2018 Wiley Periodicals, Inc.

Hypofractionation Regimens for Stereotactic Radiotherapy for Large Brain Tumors

International Nuclear Information System (INIS)

Yuan Jiankui; Wang, Jian Z.; Lo, Simon; Grecula, John C.; Ammirati, Mario; Montebello, Joseph F.; Zhang Hualin; Gupta, Nilendu; Yuh, William T.C.; Mayr, Nina A.

2008-01-01

Purpose: To investigate equivalent regimens for hypofractionated stereotactic radiotherapy (HSRT) for brain tumor treatment and to provide dose-escalation guidance to maximize the tumor control within the normal brain tolerance. Methods and Materials: The linear-quadratic model, including the effect of nonuniform dose distributions, was used to evaluate the HSRT regimens. The α/β ratio was estimated using the Gammaknife stereotactic radiosurgery (GKSRS) and whole-brain radiotherapy experience for large brain tumors. The HSRT regimens were derived using two methods: (1) an equivalent tumor control approach, which matches the whole-brain radiotherapy experience for many fractions and merges it with the GKSRS data for few fractions; and (2) a normal-tissue tolerance approach, which takes advantages of the dose conformity and fractionation of HSRT to approach the maximal dose tolerance of the normal brain. Results: A plausible α/β ratio of 12 Gy for brain tumor and a volume parameter n of 0.23 for normal brain were derived from the GKSRS and whole-brain radiotherapy data. The HSRT prescription regimens for the isoeffect of tumor irradiation were calculated. The normal-brain equivalent uniform dose decreased as the number of fractions increased, because of the advantage of fractionation. The regimens for potential dose escalation of HSRT within the limits of normal-brain tolerance were derived. Conclusions: The designed hypofractionated regimens could be used as a preliminary guide for HSRT dose prescription for large brain tumors to mimic the GKSRS experience and for dose escalation trials. Clinical studies are necessary to further tune the model parameters and validate these regimens

Comparison of anthropometric and training characteristics between recreational male marathoners and 24-hour ultramarathoners

Directory of Open Access Journals (Sweden)

Rüst CA

2012-10-01

Full Text Available Christoph Alexander Rüst,1 Beat Knechtle,1,2 Patrizia Knechtle,2 Thomas Rosemann11Institute of General Practice and for Health Services Research, University of Zurich, Zurich, 2Gesundheitszentrum St Gallen, St Gallen, SwitzerlandBackground: Of the anthropometry and training variables used to predict race performance in a 24-hour ultrarun, the personal best marathon time is the strongest predictor in recreational male 24-hour ultramarathoners. This finding raises the question of whether similarities exist between male recreational 24-hour ultramarathoners and male recreational marathoners.Methods: The association between age, anthropometric variables (ie, body mass, body height, body mass index, percent body fat, skeletal muscle mass, limb circumference, and skinfold thickness at the pectoral, mid axillary, triceps, subscapular, abdominal, suprailiac, front thigh, and medial calf sites, previous experience and training characteristics (ie, volume, speed, and personal best time, and race time for 79 male recreational 24-hour ultramarathoners and 126 male recreational marathoners was investigated using bivariate and multivariate analysis.Results: The 24-hour ultramarathoners were older (P < 0.05, had a lower circumference at both the upper arm (P < 0.05 and thigh (P < 0.01, and a lower skinfold thickness at the pectoral, axillary, and suprailiac sites (P < 0.05 compared with the marathoners. During training, the 24-hour ultramarathoners were running for more hours per week (P < 0.001 and completed more kilometers (P < 0.001, but were running slower (P < 0.01 compared with the marathoners. In the 24-hour ultramarathoners, neither anthropometric nor training variables were associated with kilometers completed in the race (P > 0.05. In the marathoners, percent body fat (P < 0.001 and running speed during training (P < 0.0001 were related to marathon race times.Conclusion: In summary, differences in anthropometric and training predictor variables do

24-hour immunologic assessment of CD4+ and CD8+ lymphocytes in renal transplant recipients receiving chronic methylprednisolone.

Science.gov (United States)

Tornatore, K M; Reed, K; Venuto, R

1995-11-01

Glucocorticoids are commonly prescribed in the post transplant period as a component of combination immunosuppressive regimens. However, the daily 24-hour pattern of helper lymphocytes (CD4+) and suppressor cells (CD8+) during chronic methylprednisolone therapy has not been examined in renal transplant recipients in relation to glucocorticoid exposure and time post-transplant. The response of total lymphocytes, CD4+ and CD8+ lymphocytes was examined in 23 stable renal transplant recipients who received methylprednisolone for at least 8 months post-transplant. The patient's prescribed oral methylprednisolone dose (mean daily dose = 9.7 +/- 2.6 mg) was given intravenously and whole blood was sampled periodically over 24 h for lymphocyte counts and methylprednisolone concentrations. A complete blood count with differential was determined via an automated hemocytometer with CD4+ and CD8+ lymphocytes determined using flow cytometry. Methylprednisolone area under the concentration versus time curve (AUC) was determined and normalized for each patient's respective dose. A general lymphopenia resulted in all patients with a mean decrease of 61 +/- 15% and an average nadir time occurring at 6 h. The decline from baseline was 76 +/- 17% for absolute number of CD4+ and 59 +/- 18% for CD8+ lymphocytes with an average nadir time at 6 h. Twelve patients exhibited a baseline CD4+ count to be less than 688 cells/mm3 (the low end of the reference range) and the lymphocyte count of all the patients fell below this value at the nadir. Six patients had a CD8+ lymphocyte count below 380 cells/mm3 (low end of the reference range) at baseline with 21 of the 23 patients exhibiting less than 380 cells/mm3 at the nadir time. At the time of nadir, the mean CD4+ and CD8+ counts were 156 +/- 105 cells/mm3 and 256 +/- 270 cells/mm3, respectively. In 17 of the 23 patients, the CD4+ count was below 200 cells/mm3 at the time of nadir. The dose-normalized AUC of methylprednisolone ranged from 22

Efficiency of radioiodine therapy with a fix dose of I-131 in toxic thyroid adenoma

International Nuclear Information System (INIS)

Petrovski, Z

2004-01-01

Purpose: The aim of this study was to estimate the results obtained using a fix dose of I-131 in the treatment of the solitary toxic thyroid adenoma. Material and Methods: We have performed radioiodine therapy m 64 patients, 49 female (50+ 1 7 yrs) and 15 male (43+-15 yrs) with solitary toxic thyroid adenoma. 45 patients received fix dose I-131 of 850 MBq, while 19 patients were treated with calculated (MBq/gr) dose 555-1100 MBq Previously 39(64%) patients were clinically hyperthyreotic and received thyreostatic meditication which were interruptecf one week before the administration of I-131. Those patients who were euthyreotic, TSH was suppressed(<0.25 MU/m1). 61(95.3%) patients received a single dose, while 3(4, 7%) patients needed two doses. Resulting thyroid matabolism and volume of nodules were evaluated 6-48 months after treatment. Results: From 45 radioiodine treated patients with fix dose 6(9, 8%) became hypothyroidism, 36(85, 3%) euthyroidism and 3(4, 9%) recurrent hyperthyroidism, in comparison with 19 treated patients with calculated I-131 dose: 2(10, 5%) hypothyroidism, 16(84, 3%) euthyroidism and 1(5, 2%) recurrent hyperthyroidism. The size of the nodules became unpalpable m 17(26, 2%), decreased evidently in 33(52, 5%) and remained unchanged in 14(21, 3%) of the treated patients. Conclusion: A fix dose of I-131 is simple, safe and efficient in the treatment of solitary toxic thyroid adenoma. There was not significant different in incidence of late follow-up results of hypothyroidism and recurrent hyperthyroidism between fix dose and calculated MBq/gr dose. (authors)

Hormone withdrawal-associated symptoms with ethinylestradiol 20 µg/drospirenone 3 mg (24/4 regimen versus ethinylestradiol 20 µg/desogestrel 150 µg (21/7 regimen

Directory of Open Access Journals (Sweden)

Bitzer J

2015-05-01

Full Text Available Johannes Bitzer,1 Maria Jesusa Banal-Silao,2 Hans-Joachim Ahrendt,3 Jaime Restrepo,4 Marion Hardtke,5 Ulrike Wissinger-Graefenhahn,6 Dietmar Trummer7 1Department of Obstetrics and Gynecology, University Hospital of Basel, Basel, Switzerland; 2University of the Philippines College of Medicine, Manila, Philippines; 3Praxis für Frauenheilkunde, Klinische Forschung und Weiterbildung (Clinical Research and Further Education, Magdeburg, Germany; 4Centro de Investigación Clínica, Clinica Medellin Poblado, Medellin, Colombia; 5Global Clinical Development Operations, Bayer Pharma AG, Berlin, Germany; 6Global Medical Affairs Women’s Healthcare, Bayer Pharma AG, Berlin, Germany; 7Clinical Statistics Europe, Bayer Pharma AG, Berlin, Germany Objective: To assess whether the combined oral contraceptive (COC ethinylestradiol (EE 20 µg/drospirenone 3 mg taken in a 24/4-day regimen (ie, 4-day hormone-free interval is more effective than an EE 20 µg/desogestrel (DSG 150 µg COC taken in a 21/7-day regimen (ie, 7-day hormone-free interval in reducing hormone withdrawal-associated symptoms (HWAS.Methods: This double-blind, randomized study (NLM identifier: NCT01076582 was conducted at 34 centers in 12 countries. Otherwise healthy women who experienced ≥2 HWAS of headache, pelvic pain, and/or bloating when using their current COCs in a 21/7-day regimen were recruited. Subjects rated the severity of their HWAS daily on a seven-point Likert scale during a baseline cycle and during four 28-day cycles with EE/drospirenone 24/4 (n=290 or EE/DSG 21/7 (n=304. The primary variable was the mean change from baseline to cycle 4 in the composite HWAS score (sum of scores for all three symptoms during cycle days 22–28.Results: In the EE/drospirenone 24/4 group, the mean (standard deviation composite HWAS score during cycle days 22–28 was reduced from 42.2 (24.8 at baseline to 12.8 (13.4 at cycle 4 (change from baseline: -30.3 [22.9]. In the EE/DSG 21/7 group, the

Effect of fixed-dose combinations of ezetimibe plus rosuvastatin in patients with primary hypercholesterolemia: MRS-ROZE (Multicenter Randomized Study of ROsuvastatin and eZEtimibe).

Science.gov (United States)

Kim, Kyung-Jin; Kim, Sang-Hyun; Yoon, Young Won; Rha, Seung-Woon; Hong, Soon-Jun; Kwak, Choong-Hwan; Kim, Weon; Nam, Chang-Wook; Rhee, Moo-Yong; Park, Tae-Ho; Hong, Taek-Jong; Park, Sungha; Ahn, Youngkeun; Lee, Namho; Jeon, Hui-Kyung; Jeon, Dong-Woon; Han, Kyoo-Rok; Moon, Keon-Woong; Chae, In-Ho; Kim, Hyo-Soo

2016-10-01

We aimed to compare the effects of fixed-dose combinations of ezetimibe plus rosuvastatin to rosuvastatin alone in patients with primary hypercholesterolemia, including a subgroup analysis of patients with diabetes mellitus (DM) or metabolic syndrome (MetS). This multicenter eight-week randomized double-blind phase III study evaluated the safety and efficacy of fixed-dose combinations of ezetimibe 10 mg plus rosuvastatin, compared with rosuvastatin alone in patients with primary hypercholesterolemia. Four hundred and seven patients with primary hypercholesterolemia who required lipid-lowering treatment according to the ATP III guideline were randomized to one of the following six treatments for 8 weeks: fixed-dose combinations with ezetimibe 10 mg daily plus rosuvastatin (5, 10, or 20 mg daily) or rosuvastatin alone (5, 10, or 20 mg daily). Fixed-dose combination of ezetimibe plus rosuvastatin significantly reduced LDL cholesterol, total cholesterol, and triglyceride levels compared with rosuvastatin alone. Depending on the rosuvastatin dose, these fixed-dose combinations of ezetimibe plus rosuvastatin provided LDL cholesterol, total cholesterol, and triglyceride reductions of 56%-63%, 37%-43%, and 19%-24%, respectively. Moreover, the effect of combination treatment on cholesterol levels was more pronounced in patients with DM or MetS than in non-DM or non-MetS patients, respectively, whereas the effect of rosuvastatin alone did not differ between DM vs non-DM or MetS vs non-MetS patients. Fixed-dose combinations of ezetimibe and rosuvastatin provided significantly superior efficacy to rosuvastatin alone in lowering LDL cholesterol, total cholesterol, and triglyceride levels. Moreover, the reduction rate was greater in patients with DM or MetS. © 2016 The Authors Cardiovascular Therapeutics Published by John Wiley & Sons Ltd.

Microbiological efficacy and tolerability of a single-dose regimen of 1 g of ceftriaxone in men with gonococcal urethritis.

Science.gov (United States)

Ito, Shin; Yasuda, Mitsuru; Hatazaki, Kyoko; Mizutani, Kosuke; Tsuchiya, Tomohiro; Yokoi, Shigeaki; Nakano, Masahiro; Deguchi, Takashi

2016-09-01

We treated men with gonococcal urethritis with a single-dose regimen of 1 g of ceftriaxone, which is recommended as the first-line treatment for gonorrhoea in Japan, to determine its microbiological outcomes and tolerability. We enrolled 255 men with gonococcal urethritis and treated them with a single-dose regimen of 1 g of ceftriaxone. We evaluated its microbiological outcomes and tolerability. We also determined ceftriaxone MICs for pretreatment isolates of Neisseria gonorrhoeae collected from the patients. The microbiological efficacy of the ceftriaxone regimen, which was determined between 5 and 9 days after treatment in 111 men based on the Japanese guideline for clinical research on antimicrobial agents in urogenital infections, was 100%. In the 194 men who returned to the clinic between 2 and 41 days after treatment, 191 (98.5%; 95% CI 96.8%-100%) were negative for N. gonorrhoeae after treatment. Ceftriaxone MICs determined for 136 pretreatment isolates obtained from these 194 men ranged from 0.001 to 0.25 mg/L. One isolate persisting after treatment exhibited a ceftriaxone MIC of 0.008 mg/L. For two isolates persisting after treatment, ceftriaxone MICs were not determined. Seven adverse events were observed in 7 (3.2%) of the 220 men treated with the ceftriaxone regimen. Four men had diarrhoea classified as grade 1. Three had urticaria during ceftriaxone administration, with one event classified as grade 1 and two events classified as grade 3. A single-dose regimen of 1 g of ceftriaxone was microbiologically effective against gonococcal urethritis and was safe and tolerable. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

A rational quantitative approach to determine the best dosing regimen for a target therapeutic effect: a unified formalism for antibiotic evaluation.

Science.gov (United States)

Li, Jun; Nekka, Fahima

2013-02-21

The determination of an optimal dosing regimen is a critical step to enhance the drug efficacy and avoid toxicity. Rational dosing recommendations based on mathematical considerations are increasingly being adopted in the process of drug development and use. In this paper, we propose a quantitative approach to evaluate the efficacy of antibiotic agents. By integrating both pharmacokinetic (PK) and pharmacodynamic (PD) information, this approach gives rise to a unified formalism able to measure the cause-effect of dosing regimens. This new pharmaco-metric allows to cover a whole range of antibiotics, including the two well known concentration and time dependent classes, through the introduction of the Hill-dependency concept. As a direct fallout, our formalism opens a new path toward the bioequivalence evaluation in terms of PK and PD, which associates the in vivo drug concentration and the in vitro drug effect. Using this new approach, we succeeded to reveal unexpected, but relevant behaviors of drug performance when different drug regimens and drug classes are considered. Of particular notice, we found that the doses required to reach the same therapeutic effect, when scheduled differently, exhibit completely different tendencies for concentration and time dependent drugs. Moreover, we theoretically confirmed the previous experimental results of the superiority of the once daily regimen of aminoglycosides. The proposed methodology is appealing for its computational features and can easily be applicable to design fair clinical protocols or rationalize prescription decisions. Copyright © 2012 Elsevier Ltd. All rights reserved.

Development of Sustained Release "NanoFDC (Fixed Dose Combination" for Hypertension - An Experimental Study.

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Anjuman Arora

Full Text Available The present study was planned to formulate, characterize and evaluate the pharmacokinetics of a novel "NanoFDC" comprising three commonly prescribed anti-hypertensive drugs, hydrochlorothiazide (a diuretic, candesartan (ARB and amlodipine (a calcium channel blocker.The candidate drugs were loaded in Poly (DL-lactide-co-gycolide (PLGA by emulsion- diffusion-evaporation method. The formulations were evaluated for their size, morphology, drug loading and in vitro release individually. Single dose pharmacokinetic profiles of the nanoformulations alone and in combination, as a NanoFDC, were evaluated in Wistar rats.The candidate drugs encapsulated inside PLGA showed entrapment efficiencies ranging from 30%, 33.5% and 32% for hydrochlorothiazide, candesartan and amlodipine respectively. The nanoparticles ranged in size from 110 to 180 nm. In vitro release profile of the nanoformulation showed 100% release by day 6 in the physiological pH 7.4 set up with PBS (phosphate buffer saline and by day 4-5 in the intestinal pH 1.2 and 8.0 set up SGF (simulated gastric fluid and SIF (simulated intestinal fluid respectively. In pharmacokinetic analysis a sustained-release for 6 days and significant increase in the mean residence time (MRT, as compared to the respective free drugs was noted [MRT of amlodipine, hydrochlorothiazide and candesartan changed from 8.9 to 80.59 hours, 11 to 69.20 hours and 9 to 101.49 hours respectively].We have shown for the first time that encapsulating amlodipine, hydrochlorothiazide and candesartan into a single nanoformulation, to get the "NanoFDC (Fixed Dose Combination" is a feasible strategy which aims to decrease pill burden.

Desfechos clínicos do tratamento de tuberculose utilizando o esquema básico recomendado pelo Ministério da Saúde do Brasil com comprimidos em dose fixa combinada na região metropolitana de Goiânia Clinical treatment outcomes of tuberculosis treated with the basic regimen recommended by the Brazilian National Ministry of Health using fixed-dose combination tablets in the greater metropolitan area of Goiânia, Brazil

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Anna Carolina Galvão Ferreira

2013-02-01

Full Text Available OBJETIVO: Descrever as taxas de cura, falência e abandono do tratamento da tuberculose com o esquema básico preconizado pelo Ministério da Saúde (tratamento com rifampicina, isoniazida, pirazinamida e etambutol por dois meses seguido de isoniazida e rifampicina por quatro meses utilizando comprimidos em dose fixa combinada em regime autoadministrado e descrever os eventos adversos e seus possíveis impactos nos desfechos do tratamento. MÉTODOS: Estudo descritivo utilizando dados coletados prospectivamente dos prontuários médicos de pacientes com tuberculose (idade > 18 anos tratados com o esquema básico em duas unidades básicas de saúde da região metropolitana de Goiânia, GO. RESULTADOS: A amostra foi composta por 40 pacientes com tuberculose. A taxa de cura foi de 67,5%, a taxa de abandono foi de 17,5%, e não ocorreram casos de falência. Nessa amostra, 19 pacientes (47% relataram reações adversas aos medicamentos. Essas foram leves e moderadas, respectivamente, em 87% e 13% dos casos. Em nenhum caso houve necessidade de mudança do esquema ou suspensão do tratamento. CONCLUSÕES: A taxa de cura do esquema básico com o uso de comprimidos em dose fixa combinada sob regime autoadministrado foi semelhante às taxas históricas do esquema anterior. A taxa de abandono, na amostra estudada, foi muito acima da taxa preconizada como adequada (até 5%.OBJECTIVE: To describe the rates of cure, treatment failure, and treatment abandonment obtained with the basic regimen recommended by the Brazilian National Ministry of Health (rifampin, isoniazid, pyrazinamide, and ethambutol for two months, followed by isoniazid and rifampin for four months involving the use of fixed-dose combination tablets (self-administered treatment, as well as to describe adverse events and their potential impact on treatment outcomes. METHODS: This was a descriptive study based on prospective data obtained from the medical records of tuberculosis patients (> 18

The effect of continuous low dose methylprednisolone infusion on inflammatory parameters in patients undergoing coronary artery bypass graft surgery: a randomized-controlled clinical trial.

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Abbas Ghiasi

2015-02-01

Full Text Available This trial was performed to determine if a continuous low-dose infusion of methylprednisolone is as effective as its bolus of high-dose in reducing inflammatory response. The study was single-center, double-blinded randomized clinical trial and performed in a surgical intensive care unit of an academic hospital. In this study, 72 consecutive patients undergoing elective coronary artery bypass grafting (CABG were assigned to receive either a methylprednisolone loading dose (1mg/kg followed by continuous infusion (2mg/Kg/24 hours for 1 day (low-dose regime or a single dose of methylprednisolone (15 mg/kg before cardiopulmonary bypass (high dose regime. Serum concentrations of IL-6 and C- reactive protein (CRP were measured preoperatively and 6, 24 and 48 hours after surgery, and serum creatinine was measured before the operation and 24, 48 and 72 hours postoperatively. The measurements were then compared between the groups to evaluate the efficacy of each regimen. The basic characteristics and measurements were not different between the study groups. There was no significant difference in IL-6 and CRP elevation (P=0.52 and P=0.46, respectively. Early outcomes such as the length of stay in the intensive care unit, intubation time, changes in serum creatinine and blood glucose levels, inotropic support, insulin requirements, and rate of infection were also similar in both groups. A continuous low dose infusion of methylprednisolone was as effective as a single high dose methylprednisolone in reducing the inflammatory response after CABG with extracorporeal circulation with no significant difference in the postoperative measurements and outcomes.

Fixed Dose Combination for TB treatment

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Tjandra Y. Aditama

2003-06-01

Full Text Available According to the World Health Organization, a third of the world’s population is infected with tuberculosis. The disease is responsible for nearly 2 million deaths each year and over 8 million were developing active diseases. Moreover, according to WHO (2000, tuberculosis deaths are estimated to increase to 35 million between 2000-2020. The majority of tuberculosis patients worldwide are still treated with single drugs, or with 2-drug fixed-dose combinations (FDCs. To improve tuberculosis treatment, 2- and 3-drug FDCs were recommended by the World Health Organization (WHO as part of the DOTS strategy. Since 1999 a 4-drug FDC was included on the WHO Model List of Essential Drugs. Today, FDCs are important tools to further improve the quality of care for people with TB, and accelerate DOTS expansion to reach the global TB control targets. Fixed dose combination TB drugs could simplifies both treatment and management of drug supply, and may prevent the emergence of drug resistance .Prevention of drug resistance is just one of the potential benefits of the use of FDCs. FDCs simplify administration of drugs by reducing the number of pills a patient takes each day and decreasing the risk of incorrect prescriptions. Most tuberculosis patients need only take 3–4 FDCs tablets per day during the intensive phase of treatment, instead of the 15–16 tablets per day that is common with single-drug formulations It is much simpler to explain to patients that they need to take four tablets of the same type and colour, rather than a mixture of tablets of different shapes, colours and sizes. Also, the chance of taking an incomplete combination of drugs is eliminated, since the four essential drugs are combined into one tablet. FDCs are also simpler for care-givers as they minimize the risk of confusion. Finally, drug procurement, in all its components (stock management, shipping, distribution, is simplified by FDCs. Adverse reactions to drugs are not more

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

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

2017-01-01

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

Total effective dose equivalent associated with fixed uranium surface contamination

International Nuclear Information System (INIS)

Bogard, J.S.; Hamm, R.N.; Ashley, J.C.; Turner, J.E.; England, C.A.; Swenson, D.E.; Brown, K.S.

1997-04-01

This report provides the technical basis for establishing a uranium fixed-contamination action level, a fixed uranium surface contamination level exceeding the total radioactivity values of Appendix D of Title 10, Code of Federal Regulations, part 835 (10CFR835), but below which the monitoring, posting, and control requirements for Radiological Areas are not required for the area of the contamination. An area of fixed uranium contamination between 1,000 dpm/100 cm 2 and that level corresponding to an annual total effective dose equivalent (TEDE) of 100 mrem requires only routine monitoring, posting to alert personnel of the contamination, and administrative control. The more extensive requirements for monitoring, posting, and control designated by 10CFR835 for Radiological Areas do not have to be applied for these intermediate fixed-contamination levels

Comparison of the bronchodilatation produced by inhalation of ipratropium bromide and salbutamol sequentially and in fixed dose combination in stable bronchial asthma patients

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Mohan A

2006-01-01

Full Text Available Objectives : The combination of a 43-2 agonist and an anticholinergic agent is of-ten used to manage bronchial asthma. However, it is unclear whether these drugs should be given separately in sequence or in a fixed dose combination for maximum effect. Methods : 27 patients with stable bronchial asthma were given the above two drugs in two separate sessions one week apart. In one session they were given the above two drugs as a fixed dose combination and in the other session, they were given se-quentially with salbutamol following ipratropium after 30 minutes. Spirometry was performed at baseline and 15, 30 and 60 minutes after inhaling the second drug. Results : Both groups showed significant improvement in forced vital capacity (FVC, forced expiratory time in one second (FEV 1 , peak expiratory flow rate (PEFR and forced expiratory flow (FEF 25-75 from baseline upto one hour. FVC increased initially and then stabilized; however, the increase was more sustained in the group getting combination treatment. This group also showed a higher rise in FEV 1 (p=0.02. Both FEV 1 and FEF 25-75 decreased after 30 minutes in the group that received sequential therapy. PEFR increased continuously till 60 minutes in both groups and there was no significant difference between them (p=0.98. Interpretation and Conclusion: Both methods of drug dosing produce equivalent bronchodilation. Fixed dose combinations produced a more sustained rise in FVC and higher increase in FEV 1 . Hence fixed dose combinations are more effective short-term bronchodilators and give an added advantage of reducing the number of inhalers required, thus improv-ing compliance.

A Comparison of 4- and 24-Hour Urine Samples for the Diagnosis of Proteinuria in Pregnancy

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Afsane Amirabi

2011-09-01

Full Text Available Background: Preeclampsia is a serious complication of pregnancy, and it is vital to diagnosis the condition as early as possible. Proteinuria is an important symptom of preeclampsia, and repeated urine analysis to screen for the condition is part of the standard antenatal care. The purpose of this study was to determine the correlation between 4- and 24-hour urine total protein values to examine whether the 4-hour urine samples could be used for the diagnosis of proteinuria in hypertensive disorders of pregnancy. Methods: A cross-sectional study was performed on 110 pregnant (after gestational week 20 of pregnancy patients who were hypertensive (blood pressure ≥140/90 mmHg and had proteinuria as defined by positive urinary protein of at least 1+ in dipstick. Patients' urine samples were collected over 24 hours; the first 4 hours were collected separately from the next 20-hours. Patients, who did not collect the 24-hour urine, were excluded from the study. One hundred patients met the criteria, and were included in the study. The urine volume, total protein and creatinine levels of 4- and 24-hours samples were measured. The correlation between 4-hour and 24-hour samples was examined using Pearson correlation test. Results: Of the 100 patients, 42 had no proteinuria, 44 had mild proteinuria, and 14 had severe proteinuria. The urine protein values of 4-hour samples correlated with those of the 24-hours samples for patients with mild and severe forms of the disease (P<0.001, r=0.86. Conclusion: This study showed there was a correlation between 4-hour and 24-hour urine proteins. The finding indicates that a random 4-hour sample might be used for the initial assessment of proteinuria

Non-24-hour sleep-wake disorder revisited – A case study

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Corrado eGarbazza

2016-02-01

Full Text Available The human sleep-wake cycle is governed by two major factors: a homeostatic hourglass process (process S, which rises linearly during the day, and a circadian process C, which determines the timing of sleep in an approximately 24h rhythm in accordance to the external light-dark (LD cycle. While both individual processes are fairly well characterized, the exact nature of their interaction remains unclear. The circadian rhythm is generated by the subthalamic nucleus (SCN, master clock of the anterior hypothalamus, through cell-autonomous feedback loops of DNA transcription and translation. While the phase length (tau of the cycle is relatively stable and genetically determined, the phase of the clock is reset by external stimuli (zeitgebers, the most important being the LD-cycle. Misalignments of the internal rhythm with the LD-cycle can lead to various somatic complaints and ultimately to the development of circadian rhythm sleep disorders (CRSD. Non-24-h sleep-wake disorders (N24HSWD is a CRSD affecting up to 50% of totally blind patients and characterized by the inability to maintain a stable entrainment of the typically long circadian rhythm (tau >24.5h to the LD- cycle. The disease is rare (<1:1 Mio in sighted individuals and the pathophysiology less well understood.Here we present the case of a 40 year old sighted male, who developed a misalignment of the internal clock with the external light-dark cycle following the treatment for Hodgkin’s lymphoma (ABVD regimen, 4 cycles and AVD regimen, 4 cycles. A thorough clinical assessment including actigraphy, melatonin profiles, polysomnography and wake-EEG lead to the diagnosis of a non-24-h sleep-wake disorders (N24HSWD with a free-running rhythm of tau=25.5h. A therapeutic intervention with bright-light therapy (BLT, 30 min 10.000lux in the morning and melatonin administration (0.5-0.75 mg in the evening failed to entrain the free-running rhythm, although a longer treatment duration and more

Ocular pharmacokinetics and tolerability of bimatoprost ophthalmic solutions administered once or twice daily in rabbits, and clinical dosing implications

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Shen J

2017-09-01

Full Text Available Jie Shen,1 Margot L Goodkin,2 Warren Tong,2 Mayssa Attar3 1Clinical Pharmacology, 2Clinical Development, 3Clinical Pharmacology, Metabolism and Immunology, Allergan plc, Irvine, CA, USA Purpose: Fixed-combination medications can benefit patients requiring multiple agents to lower their intraocular pressure (IOP, but combining agents with complementary mechanisms of action is challenging if their dosing frequency differs. This study compares in vivo pharmacokinetic and ocular tolerability of bimatoprost 0.01% ophthalmic solutions dosed once or twice daily. Reports of twice-daily dosing in glaucoma patients are also reviewed.Methods: New Zealand White rabbits were administered bimatoprost 0.01% monotherapy or fixed-combination bimatoprost 0.01%/brimonidine 0.1%, once or twice daily in both eyes for 4 days. Ocular tissues were harvested and analyzed by liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters calculated included maximum observed concentration, time to maximum concentration, and area under the concentration-time curve.Results: Due to extensive metabolism, bimatoprost concentration was below the quantitation limit by 1 hour post-dose in all samples. Bimatoprost acid exposure, however, could be measured up to 6–8 hours post-dose and was similar in the aqueous humor and iris-ciliary body (pharmacological site of action of animals treated once or twice daily with either bimatoprost 0.01% or fixed-combination bimatoprost 0.01%/brimonidine 0.1%. Increasing dosage frequency in rabbits did not raise the incidence of drug-related conjunctival hyperemia (most common adverse event associated with bimatoprost use in humans, suggesting comparable ocular tolerability of the once- and twice-daily regimens for each formulation.Conclusion: Bimatoprost 0.01% administered once or twice daily as monotherapy and in fixed-combination with brimonidine 0.1% in rabbits show similar pharmacokinetic profiles of bimatoprost acid

Results of Hematopoietic Stem Cell Transplantation After Treatment With Different High-Dose Total-Body Irradiation Regimens in Five Dutch Centers

International Nuclear Information System (INIS)

Loes van Kempen-Harteveld, M.; Brand, Ronald; Kal, Henk B.; Verdonck, Leo F.; Hofman, Pieter; Schattenberg, Anton V.; Maazen, Richard W. van der; Cornelissen, Jan J.; Eijkenboom, Wil M.H.; Lelie, Johannes P. van der; Oldenburger, Foppe; Barge, Renee M.; Biezen, Anja van; Vossen, Jaak M.J.J.; Noordijk, Evert M.; Struikmans, Henk

2008-01-01

Purpose: To evaluate results of high-dose total-body irradiation (TBI) regimens for hematopoietic stem cell transplantation. Methods and Materials: A total of 1,032 patients underwent TBI in one or two fractions before autologous or allogeneic hematologic stem cell transplantation for acute leukemia and non-Hodgkin's lymphoma. The TBI regimens were normalized by using the biological effective dose (BED) concept. The BED values were divided into three dose groups. Study end points were relapse incidence (RI), non-relapse mortality (NRM), relapse-free survival (RFS), and overall survival (OS). Multivariate analysis was performed, stratified by disease. Results: In the highest TBI dose group, RI was significantly lower and NRM was higher vs. the lower dose groups. However, a significant influence on RFS and OS was not found. Relapses in the eye region were found only after shielding to very low doses. Age was of significant influence on OS, RFS, and NRM in favor of younger patients. The NRM of patients older than 40 years significantly increased, and OS decreased. There was no influence of age on RI. Men had better OS and RFS and lower NRM. Type of transplantation significantly influenced RI and NRM for patients with acute leukemia and non-Hodgkin's lymphoma. There was no influence on RFS and OS. Conclusions: Both RI and NRM were significantly influenced by the size of the BED of single-dose or two-fraction TBI regimens; OS and RFS were not. Age was of highly significant influence on NRM, but there was no influence of age on RI. Hyperfractionated TBI with a high BED might be useful, assuming NRM can be reduced

Lean body mass as an independent determinant of dose-limiting toxicity and neuropathy in patients with colon cancer treated with FOLFOX regimens

International Nuclear Information System (INIS)

Ali, Raafi; Sawyer, Michael B.; Bianchi, Laurent; Roberts, Sarah; Mollevi, Caroline; Senesse, Pierre; Baracos, Vickie E.; Assenat, Eric

2016-01-01

Evidence suggests that lean body mass (LBM) may be useful to normalize chemotherapy doses. Data from one prospective and one retrospective study were used to determine if the highest doses of oxaliplatin/kg LBM within FOLFOX regimens would be associated with dose-limiting toxicity (DLT) in colon cancer patients. Toxicity over four cycles was graded according to NCI Common Toxicity Criteria V2 or V3 (Common Terminology Criteria for Adverse Events, National Cancer Institute, Bethesda, MD). Muscle tissue was measured by computerized tomography (CT) and used to evaluate the LBM compartment of the whole body. In prospective randomized clinical trials conducted in France (n = 58), for patients given FOLFOX-based regimens according to body surface area, values of oxaliplatin/kg LBM were highly variable, ranging from 2.55 to 6.6 mg/kg LBM. A cut point of 3.09 mg oxaliplatin/kg LBM for developing toxicity was determined by Receiver Operating Characteristic (ROC) analysis, below this value 0/17 (0.0%) of patients experienced DLT; in contrast above this value 18/41 (44.0%) of patients were dose reduced or had treatment terminated owing to toxicity (≥Grade 3 or neuropathy ≥Grade 2); for 9/41 the DLT was sensory neuropathy. These findings were validated in an independent cohort of colon cancer patients (n = 80) receiving FOLFOX regimens as part of standard care, in Canada. Low LBM is a significant predictor of toxicity and neuropathy in patients administered FOLFOX-based regimens using conventional body surface area (BSA) dosing

Efficacy of fix dose combination (atorvastatin and amlodipine) in treatment of uncontrolled hypertension and dyslipidemia

International Nuclear Information System (INIS)

Bashir, S.; Sherwani, M.U.K.; Batool, A.

2012-01-01

The fixed-dose combination containing the antihypertensive agent amlodipine and the statin, atorvastatin, is the first combination of its kind designed to treat two risk factors for cardiovascular disease (CVD), i.e., hypertension and dyslipidemia. in this study, blood pressure and lipid lowering effects of combination of amlodipine and atorvastatin were evaluated in uncontrolled hypertensive patients. Methods: Thirty patients both male and female in the age group 35-60 years attending the hypertensive clinic of PMRC FJMC suffering from uncontrolled hypertension were selected. baseline blood pressure was checked after half hour rest in sitting and standing position using mercury sphygmomanometer. Blood sample was collected from all patients after overnight fasting for assessment of serum cholesterol, triglycerides, LDL and HDL cholesterol levels. they were prescribed with fixed dose combination of 5 mg amlodipine and 10 mg atorvastatin. Patients were followed for their blood pressure measurement after every 4 weeks up to 12 weeks. At the end of 12 weeks their fasting blood sample was taken again for determination of serum cholesterol, triglyceride, IDL and HDL cholesterol levels. Results: Systolic blood pressure after 4, 8 and 12 weeks was significantly lower at all intervals from baseline. when systolic blood pressure after 8 and 12 weeks was compared with 4 weeks, the effect was again significant (p=0.024, p=0.002 respectively). There was no significant reduction seen in 8 versus 12 weeks (p=0.493). Diastolic blood pressure at 4, 8 and 12 weeks was significantly lower from baseline. Diastolic blood pressure after 4 and 8 weeks when compared with 8 and 12 weeks was not significantly low (p=0.99 and 0.91 respectively). Lipid profile of the patients was significantly reduced from baseline after twelve weeks of fixed dose combination of treatment (p<0.000). Conclusion: Combination therapy proved to be effective in controlling hypertension and dyslipidemia than single

Efficacy of fix dose combination (atorvastatin and amlodipine) in treatment of uncontrolled hypertension and dyslipidemia

Energy Technology Data Exchange (ETDEWEB)

Bashir, S; Sherwani, M U.K.; Batool, A [Fatima Jinnah Medical College, Lahore (Pakistan)

2012-07-15

The fixed-dose combination containing the antihypertensive agent amlodipine and the statin, atorvastatin, is the first combination of its kind designed to treat two risk factors for cardiovascular disease (CVD), i.e., hypertension and dyslipidemia. in this study, blood pressure and lipid lowering effects of combination of amlodipine and atorvastatin were evaluated in uncontrolled hypertensive patients. Methods: Thirty patients both male and female in the age group 35-60 years attending the hypertensive clinic of PMRC FJMC suffering from uncontrolled hypertension were selected. baseline blood pressure was checked after half hour rest in sitting and standing position using mercury sphygmomanometer. Blood sample was collected from all patients after overnight fasting for assessment of serum cholesterol, triglycerides, LDL and HDL cholesterol levels. they were prescribed with fixed dose combination of 5 mg amlodipine and 10 mg atorvastatin. Patients were followed for their blood pressure measurement after every 4 weeks up to 12 weeks. At the end of 12 weeks their fasting blood sample was taken again for determination of serum cholesterol, triglyceride, IDL and HDL cholesterol levels. Results: Systolic blood pressure after 4, 8 and 12 weeks was significantly lower at all intervals from baseline. when systolic blood pressure after 8 and 12 weeks was compared with 4 weeks, the effect was again significant (p=0.024, p=0.002 respectively). There was no significant reduction seen in 8 versus 12 weeks (p=0.493). Diastolic blood pressure at 4, 8 and 12 weeks was significantly lower from baseline. Diastolic blood pressure after 4 and 8 weeks when compared with 8 and 12 weeks was not significantly low (p=0.99 and 0.91 respectively). Lipid profile of the patients was significantly reduced from baseline after twelve weeks of fixed dose combination of treatment (p<0.000). Conclusion: Combination therapy proved to be effective in controlling hypertension and dyslipidemia than single

Treatment of Amblyopia Using Personalized Dosing Strategies: Statistical Modelling and Clinical Implementation.

Science.gov (United States)

Wallace, Michael P; Stewart, Catherine E; Moseley, Merrick J; Stephens, David A; Fielder, Alistair R

2016-12-01

To generate a statistical model for personalizing a patient's occlusion therapy regimen. Statistical modelling was undertaken on a combined data set of the Monitored Occlusion Treatment of Amblyopia Study (MOTAS) and the Randomized Occlusion Treatment of Amblyopia Study (ROTAS). This exercise permits the calculation of future patients' total effective dose (TED)-that predicted to achieve their best attainable visual acuity. Daily patching regimens (hours/day) can be calculated from the TED. Occlusion data for 149 study participants with amblyopia (anisometropic in 50, strabismic in 43, and mixed in 56) were analyzed. Median time to best observed visual acuity was 63 days (25% and 75% quartiles; 28 and 91 days). Median visual acuity in the amblyopic eye at start of occlusion was 0.40 logMAR (quartiles 0.22 and 0.68 logMAR) and at end of occlusion was 0.12 (quartiles 0.025 and 0.32 logMAR). Median lower and upper estimates of TED were 120 hours (quartiles 34 and 242 hours), and 176 hours (quartiles 84 and 316 hours). The data suggest a piecewise linear relationship (P = 0.008) between patching dose-rate (hours/day) and TED with a single breakpoint estimated at 2.16 (standard error 0.51) hours/day, suggesting doses below 2.16 hours/day are less effective. We introduce the concept of TED of occlusion. Predictors for TED are visual acuity deficit, amblyopia type, and age at start of occlusion therapy. Dose-rates prescribed within the model range from 2.5 to 12 hours/day and can be revised dynamically throughout treatment in response to recorded patient compliance: a personalized dosing strategy.

24-hour whole-body retention of sup(99m)Tc-diphosphonate

International Nuclear Information System (INIS)

Kapitola, J.

1985-01-01

A new method is described for the examination of bone tissue metabolism; a 24-hour retention of diphosphonate labelled with radioactive sup(99m)Tc (assessed using a whole-body counter or by estimation of the amount of labelled substance excreted in the course of 24 hours via the urine). The values are elevated in primary hyperparathyroidism, osteomalacia, generalized Paget's disease, multiple bone metastases; the values are not uniform in osteoporosis. The method is simple, sensitive and reliable (provided renal function is normal), suited for screening, as part of specialized osteological diagnosis as well as for repeated longitudinal investigations. (author)

Diagnostic and Treatment Challenges of Sighted Non-24-Hour Sleep-Wake Disorder.

Science.gov (United States)

Malkani, Roneil G; Abbott, Sabra M; Reid, Kathryn J; Zee, Phyllis C

2018-04-15

To report the diagnostic and treatment challenges of sighted non-24-hour sleep-wake disorder (N24SWD). We report a series of seven sighted patients with N24SWD clinically evaluated by history and sleep diaries, and when available wrist actigraphy and salivary melatonin levels, and treated with timed melatonin and bright light therapy. Most patients had a history of a delayed sleep-wake pattern prior to developing N24SWD. The typical sleep-wake pattern of N24SWD was seen in the sleep diaries (and in actigraphy when available) in all patients with a daily delay in midpoint of sleep ranging 0.8 to 1.8 hours. Salivary dim light melatonin onset (DLMO) was evaluated in four patients but was missed in one. The estimated phase angle from DLMO to sleep onset ranged from 5.25 to 9 hours. All six patients who attempted timed melatonin and bright light therapy were able to entrain their sleep-wake schedules. Entrainment occurred at a late circadian phase, possibly related to the late timing of melatonin administration, though the patients often preferred late sleep times. Most did not continue treatment and continued to have a non-24-hour sleep-wake pattern. N24SWD is a chronic debilitating disorder that is often overlooked in sighted people and can be challenging to diagnose and treat. Tools to assess circadian pattern and timing can be effectively applied to aid the diagnosis. The progressive delay of the circadian rhythm poses a challenge for determining the most effective timing for melatonin and bright light therapies. Furthermore, once the circadian sleep-wake rhythm is entrained, long-term effectiveness is limited because of the behavioral and environmental structure that is required to maintain stable entrainment. © 2018 American Academy of Sleep Medicine.

Assessment of bioequivalence of rifampicin, isoniazid and pyrazinamide in a four drug fixed dose combination with separate formulations at the same dose levels.

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Agrawal, Shrutidevi; Kaur, Kanwal Jit; Singh, Inderjit; Bhade, Shantaram R; Kaul, Chaman Lal; Panchagnula, Ramesh

2002-02-21

Tuberculosis (TB) needs treatment with three to five different drugs simultaneously, depending on the patient category. These drugs can be given as single drug preparations or fixed dose combinations (FDCs) of two more drugs in a single formulation. World Health Organization and International Union against Tuberculosis and Lung Disease (IUATLD) recommend FDCs only of proven bioavailability. The relative bioavailability of rifampicin (RIF), isoniazid (INH) and pyrazinamide (PYZ) was assessed on a group of 13 healthy male subjects from a four drug FDC versus separate formulations at the same dose levels. The study was designed to be an open, crossover experiment. A total of nine blood samples each of 3 ml volume were collected over a period of 24-h. The concentrations of RIF, its main metabolite desacetyl RIF (DRIF), INH and PYZ in plasma were assessed by HPLC analysis. Pharmacokinetic parameters namely AUC(0-24), AUC(0-inf), C(max), T(max), were calculated and subjected to different statistical tests (Hauschke analysis, two way ANOVA, normal and log transformed confidence interval) at 90% confidence interval. In addition, elimination rate constant (K(el)) and absorption efficiencies for each drug were also calculated. It was concluded that four drugs FDC tablet is bioequivalent for RIF, INH and PYZ to separate formulation at the same dose levels.

Cost-utility analysis of the fixed-dose combination of dolutegravir/abacavir/lamivudine as initial treatment of HIV+ patients in Spain

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Santiago Moreno Guillen

2017-09-01

Full Text Available Objective: Fixed-dose combinations of antiretroviral drugs have meant an important step forward in simplifying treatment and improving compliance and has led to an increased effectiveness of therapy, a viral load decrease and improving the quality of life of patients. The single-table formulation of dolutegravir with abacavir and lamivudine (DTG/ABC/3TC is a highly efficacious and well-tolerated once-daily regimen for HIV-infected patients. The objective of the study was to assess the incremental cost-utility ratio of the fixed-dose combination of (DTG/ABC/3TC versus the combinations emtricitabine/tenofovir/efavirenz (FTC/TDF/EFV, and darunavir/r (DRV/r or raltegravir (RAL with emtricitabine/tenofovir (FTC/TDF or abacavir/lamivudine (ABC/3TC as initial antiretroviral therapy in patients infected with HIV-1 from the perspective of the Spanish National Health System. Method: The ARAMIS model, which uses a microsimulation approach to simulate the individual changes in each patient from the start of treatment to death through a Markov chain of descriptive health states of the disease, was adapted to Spain. The alternatives used for comparison were the fixed-dose combination of emtricitabine/tenofovir/efavirenz (FTC/TDF/EFV, and the fixed- dose combinations of emtricitabine/tenofovir (FTC/TDF or abacavir/lamivudine (ABC/3TC with darunavir/r (DRV/r or raltegravir (RAL. The probability of achieving virological suppression by the treatments included in the model was obtained from clinical trials SINGLE, SPRING-2 and FLAMINGO and the costs were expressed in € (2015. The model use the perspective of the Spanish National Health System, with a lifetime horizon and a discount rate of 3% was applied to cost and effectiveness. Results: Treatment initiation with DTG/ABC/3TC was dominant when it was compared with treatment initiation with all the comparators: vs. FTC/TDF/EFV (-67 210.71€/QALY, vs. DRV/r + FTC/TDF or ABC/3TC (-1 787 341.44€/QALY, and vs

Use of Monte Carlo Simulations to Determine Optimal Carbapenem Dosing in Critically Ill Patients Receiving Prolonged Intermittent Renal Replacement Therapy.

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Lewis, Susan J; Kays, Michael B; Mueller, Bruce A

2016-10-01

Pharmacokinetic/pharmacodynamic analyses with Monte Carlo simulations (MCSs) can be used to integrate prior information on model parameters into a new renal replacement therapy (RRT) to develop optimal drug dosing when pharmacokinetic trials are not feasible. This study used MCSs to determine initial doripenem, imipenem, meropenem, and ertapenem dosing regimens for critically ill patients receiving prolonged intermittent RRT (PIRRT). Published body weights and pharmacokinetic parameter estimates (nonrenal clearance, free fraction, volume of distribution, extraction coefficients) with variability were used to develop a pharmacokinetic model. MCS of 5000 patients evaluated multiple regimens in 4 different PIRRT effluent/duration combinations (4 L/h × 10 hours or 5 L/h × 8 hours in hemodialysis or hemofiltration) occurring at the beginning or 14-16 hours after drug infusion. The probability of target attainment (PTA) was calculated using ≥40% free serum concentrations above 4 times the minimum inhibitory concentration (MIC) for the first 48 hours. Optimal doses were defined as the smallest daily dose achieving ≥90% PTA in all PIRRT combinations. At the MIC of 2 mg/L for Pseudomonas aeruginosa, optimal doses were doripenem 750 mg every 8 hours, imipenem 1 g every 8 hours or 750 mg every 6 hours, and meropenem 1 g every 12 hours or 1 g pre- and post-PIRRT. Ertapenem 500 mg followed by 500 mg post-PIRRT was optimal at the MIC of 1 mg/L for Streptococcus pneumoniae. Incorporating data from critically ill patients receiving RRT into MCS resulted in markedly different carbapenem dosing regimens in PIRRT from those recommended for conventional RRTs because of the unique drug clearance characteristics of PIRRT. These results warrant clinical validation. © 2016, The American College of Clinical Pharmacology.

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

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

2018-05-01

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

The Alaska earthquake, March 27, 1964: effects on hydrologic regimen

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Waller, Roger M.; Coble, R.W.; Post, Austin; McGarr, Arthur; Vorhis, Robert C.

1966-01-01

This is the fourth in a series of six reports that the U.S. Geological Survey published on the results of a comprehensive geologic study that began, as a reconnaissance survey, within 24 hours after the March 27, 1964, Magnitude 9.2 Great Alaska Earthquake and extended, as detailed investigations, through several field seasons. The 1964 Great Alaska earthquake was the largest earthquake in the U.S. since 1700. Professional Paper 544, in 5 parts, describes the effects on hydrologic regimen.

Aggressive behavior during the first 24 hours of psychiatric admission

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Vitor Crestani Calegaro

2014-09-01

Full Text Available OBJECTIVE: To investigate the association between aggression in the first 24 hours after admission and severity of psychopathology in psychiatric inpatients.METHODS: This cross-sectional study included psychiatric patients admitted to Hospital Universitário de Santa Maria, in Santa Maria, southern Brazil, from August 2012 to January 2013. At their arrival at the hospital, patients were interviewed to fill in the Brief Psychiatric Rating Scale (BPRS form, and any aggressive episodes in the first 24 hours after admission were recorded using the Overt Aggression Scale (OAS. The Mann-Whitney U test was used to compare patients according to aggressiveness: aggressive versus non-aggressive, hostile versus violent, and aggressive against others only versus self-aggressive.RESULTS: The sample was composed of 110 patients. Aggressive patients in general had higher BPRS total scores (p = 0.002 and individual component scores, and their results showed more activation (p < 0.001 and thinking disorders (p = 0.009, but less anxious-depression (p = 0.008. Violent patients had more severe psychomotor agitation (p = 0.027, hallucinations (p = 0.017 and unusual thought content (p = 0.020. Additionally, self-aggressive patients had more disorientation (p = 0.011 and conceptual disorganization (p = 0.007.CONCLUSIONS: Aggression in psychiatric patients in the first 24 hours after admission is associated with severity of psychopathology, and severity increases with severity of patient psychosis and agitation.

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

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Neeraj Kumar Barnwal

2017-01-01

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

Personalized versus standardized dosing strategies for the treatment of childhood amblyopia: study protocol for a randomized controlled trial.

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Moseley, Merrick J; Wallace, Michael P; Stephens, David A; Fielder, Alistair R; Smith, Laura C; Stewart, Catherine E

2015-04-25

Amblyopia is the commonest visual disorder of childhood in Western societies, affecting, predominantly, spatial visual function. Treatment typically requires a period of refractive correction ('optical treatment') followed by occlusion: covering the nonamblyopic eye with a fabric patch for varying daily durations. Recent studies have provided insight into the optimal amount of patching ('dose'), leading to the adoption of standardized dosing strategies, which, though an advance on previous ad-hoc regimens, take little account of individual patient characteristics. This trial compares the effectiveness of a standardized dosing strategy (that is, a fixed daily occlusion dose based on disease severity) with a personalized dosing strategy (derived from known treatment dose-response functions), in which an initially prescribed occlusion dose is modulated, in a systematic manner, dependent on treatment compliance. A total of 120 children aged between 3 and 8 years of age diagnosed with amblyopia in association with either anisometropia or strabismus, or both, will be randomized to receive either a standardized or a personalized occlusion dose regimen. To avoid confounding by the known benefits of refractive correction, participants will not be randomized until they have completed an optical treatment phase. The primary study objective is to determine whether, at trial endpoint, participants receiving a personalized dosing strategy require fewer hours of occlusion than those in receipt of a standardized dosing strategy. Secondary objectives are to quantify the relationship between observed changes in visual acuity (logMAR, logarithm of the Minimum Angle of Resolution) with age, amblyopia type, and severity of amblyopic visual acuity deficit. This is the first randomized controlled trial of occlusion therapy for amblyopia to compare a treatment arm representative of current best practice with an arm representative of an entirely novel treatment regimen based on statistical

24-hour central aortic systolic pressure and 24-hour central pulse pressure are related to diabetic complications in type 1 diabetes - a cross-sectional study

DEFF Research Database (Denmark)

Theilade, Simone; Lajer, Maria Stenkil; Hansen, Tine Willum

2013-01-01

BACKGROUND: Non-invasive measurements of 24 hour ambulatory central aortic systolic pressure (24 h-CASP) and central pulse pressure (24 h-CPP) are now feasible. We evaluate the relationship between 24 h central blood pressure and diabetes-related complications in patients with type 1 diabetes.......68) and 3.72 (1.85-7.47) and autonomic dysfunction: 3.25 (1.65-6.41), 1.64 (1.12-2.39) and 2.89 (1.54-5.42). CONCLUSIONS: 24 h-CASP and 24 h-CPP was higher in patients vs. controls and increased with diabetic complications independently of covariates. Furthermore, 24 h-CASP was stronger associated....... METHODS: The study was cross-sectional, including 715 subjects: 86 controls (C), 69 patients with short diabetes duration (diabetes (≥ 10 years) and normoalbuminuria (LN), 163...

Oral antidiabetic therapy in a large Italian sample: drug supply and compliance for different therapeutic regimens

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Vittorino Gaddi, A; Capello, F; Di Pietro, C; Cinconze, E; Rossi, E; De Sando, V; Cevenini, M; D'Alò, G

2014-01-01

Objectives: To define the main features of patients treated with oral antidiabetics, evaluating monotherapy (MT), loose-dose combination therapy (LDCT) and fixed-dose combination therapy (FDCT); to describe medication adherence to the different therapies; and to evaluate the differences in compliance with the prescribed therapy regimen among prevalent and incident patient cohorts. Study design: This study was a retrospective cohort analysis based on the ARNO database, a national record that tracks reimbursable prescription claims submitted from selected pharmacies to the Italian national health system. In total, 169,375 subjects, from an overall population of 4,040,624 were included in this study. The patients represented 12 different local health units. Each patient had at least one oral antidiabetic prescription claim (A10B ATC code). Methods: Patients were divided into four groups according to their treatment regimen during the recruitment period (1 January 2008-31 December 2008): MT, FDCT, LDCT and swi...

Off-label biologic regimens in psoriasis: a systematic review of efficacy and safety of dose escalation, reduction, and interrupted biologic therapy.

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Elizabeth A Brezinski

Full Text Available OBJECTIVES: While off-label dosing of biologic treatments may be necessary in selected psoriasis patients, no systematic review exists to date that synthesizes the efficacy and safety of these off-label dosing regimens. The aim of this systematic review is to evaluate efficacy and safety of off-label dosing regimens (dose escalation, dose reduction, and interrupted treatment with etanercept, adalimumab, infliximab, ustekinumab, and alefacept for psoriasis treatment. DATA SOURCES AND STUDY SELECTION: We searched OVID Medline from January 1, 1990 through August 1, 2011 for prospective clinical trials that studied biologic therapy for psoriasis treatment in adults. Individual articles were screened for studies that examined escalated, reduced, or interrupted therapy with etanercept, adalimumab, infliximab, ustekinumab, or alefacept. DATA SYNTHESIS: A total of 23 articles with 12,617 patients matched the inclusion and exclusion criteria for the systematic review. Data were examined for primary and secondary efficacy outcomes and adverse events including infections, malignancies, cardiovascular events, and anti-drug antibodies. The preponderance of data suggests that continuous treatment with anti-TNF agents and anti-IL12/23 agent was necessary for maintenance of disease control. Among non-responders, dose escalation with etanercept, adalimumab, ustekinumab, and alefacept typically resulted in greater efficacy than standard dosing. Dose reduction with etanercept and alefacept resulted in reduced efficacy. Withdrawal of the examined biologics led to an increase in disease activity; efficacy from retreatment did not result in equivalent initial response rates for most biologics. Safety data on off-label dosing regimens are limited. CONCLUSION: Dose escalation in non-responders generally resulted in increased efficacy in the examined biologics used to treat moderate-to-severe psoriasis. Continuous treatment with anti-TNF agents and anti-IL12/23 agent

The impact on coagulation of an intravenous loading dose in addition to a subcutaneous regimen of low-molecular-weight heparin in the initial treatment of acute coronary syndromes

NARCIS (Netherlands)

Bijsterveld, Nick R.; Moons, Arno H.; Meijers, Joost C. M.; Levi, Marcel; Büller, Harry R.; Peters, Ron J. G.

2003-01-01

OBJECTIVES We sought to quantify the impact of adding an intravenous loading dose to a subcutaneous regimen of enoxaparin in patients with an acute coronary syndrome (ACS). BACKGROUND It is unclear whether an intravenous (M loading dose of enoxaparin should be added to a subcutaneous (SQ) regimen in

Population pharmacokinetics and pharmacodynamics of hydroxyurea in sickle cell anemia patients, a basis for optimizing the dosing regimen

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Galactéros Frédéric

2011-05-01

Full Text Available Abstract Background Hydroxyurea (HU is the first approved pharmacological treatment of sickle cell anemia (SCA. The objectives of this study were to develop population pharmacokinetic(PK-pharmacodynamic(PD models for HU in order to characterize the exposure-efficacy relationships and their variability, compare two dosing regimens by simulations and develop some recommendations for monitoring the treatment. Methods The models were built using population modelling software NONMEM VII based on data from two clinical studies of SCA adult patients receiving 500-2000 mg of HU once daily. Fetal hemoglobin percentage (HbF% and mean corpuscular volume (MCV were used as biomarkers for response. A sequential modelling approach was applied. Models were evaluated using simulation-based techniques. Comparisons of two dosing regimens were performed by simulating 10000 patients in each arm during 12 months. Results The PK profiles were described by a bicompartmental model. The median (and interindividual coefficient of variation (CV of clearance was 11.6 L/h (30%, the central volume was 45.3 L (35%. PK steady-state was reached in about 35 days. For a given dosing regimen, HU exposure varied approximately fivefold among patients. The dynamics of HbF% and MCV were described by turnover models with inhibition of elimination of response. In the studied range of drug exposures, the effect of HU on HbF% was at its maximum (median Imax was 0.57, CV was 27%; the effect on MCV was close to its maximum, with median value of 0.14 and CV of 49%. Simulations showed that 95% of the steady-state levels of HbF% and MCV need 26 months and 3 months to be reached, respectively. The CV of the steady-state value of HbF% was about 7 times larger than that of MCV. Simulations with two different dosing regimens showed that continuous dosing led to a stronger HbF% increase in some patients. Conclusions The high variability of response to HU was related in part to pharmacokinetics and

Impairing DNA methylation obstructs memory enhancement for at least 24 hours in Lymnaea.

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Rothwell, Cailin M; Lukowiak, Ken D

2017-01-01

Stressor-induced memory enhancement has previously been shown to involve DNA methylation in the mollusc Lymnaea stagnalis . Specifically, injection of the DNA methylation inhibitor 5-AZA one hour before exposure to a memory-enhancing stressor obstructs memory augmentation. However, the duration of the influence of 5-AZA on this memory enhancement has not yet been examined. In this study, 2 memory-enhancing stressors (a thermal stress and exposure to the scent of a predator) were used to examine whether injection of the DNA methylation inhibitor 5-AZA 24 hours before stress exposure would still impair memory enhancement. Indeed, it was observed that memory is still obstructed when 5-AZA is injected 24 hours before exposure to either of these stressors in Lymnaea . Understanding that 5-AZA still effectively impairs memory enhancement after a period of 24 hours is valuable because it indicates that experimental manipulations do not need to be made within one hour after the injection of this DNA methylation inhibitor and can instead be made within one day (i.e. 24 hours). These results will allow for a future examination of the possible involvement of DNA methylation in memory enhancement related to longer-term stressors or environmental changes. This study further elucidates the involvement of epigenetic changes in memory enhancement in Lymnaea , providing insight into the process of memory formation in this mollusc.

36-Month Evaluation of Intravitreous Aflibercept Injection for Wet Age-Related Macular Degeneration in Patients Previously Treated With Ranibizumab or Bevacizumab.

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Conti, Felipe F; Silva, Fabiana Q; Srivastava, Sunil K; Ehlers, Justis P; Schachat, Andrew P; Singh, Rishi P

2018-03-01

In the ASSESS study, patients with neovascular age-related macular degeneration transitioned from other anti-vascular endothelial growth factor therapies to intravitreous aflibercept (Eylea; Regeneron, Tarrytown, NY) injections (IAI). The purpose was to determine the 36-month outcomes following the change from a fixed 24-month IAI dosing regimen to a routine clinical practice regimen. Patients were treated with a fixed bimonthly regimen for the first 2 years. In the third year, patients were managed according to routine clinical practice. A total of 18 patients completed the 36 months and were considered for statistical analyses. At 36 months, a nonsignificant decrease of -37.8 μm in central subfield thickness and a nonsignificant gain of 5.8 letters from baseline were observed. Despite the significant visual and anatomical gains observed in the 2 years of fixed-dosing IAI, there was gradual decline in these improvements when patients were transitioned to a variable regimen. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:179-185.]. Copyright 2018, SLACK Incorporated.

Optimizing a single fixed dose of Iodine-131 in Graves' Disease (An Experience)

International Nuclear Information System (INIS)

Khan, S.H.

2007-01-01

Full text: Kashmir is a Himalayan mountain state of India enclosed by high snow capped ridges of Pir Panjal Mountains at an average height of 4000-5000 meters above the sea level. For most of the 4 million inhabitants in this land locked valley, agriculture horticulture and handcrafts are the main source of income. Due to long and severe winters the terraced farming on the mountain slopes yield just a single crop of rice which is barely sufficient to meet the local needs of this staple diet. People are relatively poor with low annual per capita income. Goiter is endemic in the Valley of Kashmir. In a published report the overall prevalence of goiter among the school going children in Kashmir between the ages of 5 years is 45.2% (+ SEM) with urinary iodine excretion of 49 + 3.55 μg per gram of creatinine. The extremely shy people of Kashmir are casual towards the aesthetic aspects of their goiters but nevertheless seek medical advice when associated with physical symptoms. In a published study of 203 patients of thyrotoxicosis from Kashmir, Graves' disease was the commonest cause, accounting for 63% of patients. One hundred and twentyone patients of Graves' disease were prospectively studied for their response to a single fixed dose of I-131. Patients were randomly treated with two different fixed doses of I- 131. Sixty four patients belonging to Group-I received a fixed dose of 185 MBq (Low Dose) and 57 patients belonging to Group -2 received 370 MBq (High Dose) of I- 131. Following therapy all patients were evaluated at 3 months. Patients with normal or reduced thyroid hormone levels were termed as responders and those with persistently elevated levels of thyroid hormone were termed as non responders. The response rates among the two groups were analyzed for their statistical significance. Patients treated with the high fixed dose of 370 MBq revealed good response to therapy achieving a rate of 91.22%, while the response rate in the group of patients treated with

24 Hours of Sleep, Sedentary Behavior, and Physical Activity with Nine Wearable Devices

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Rosenberger, Mary E.; Buman, Matthew P.; Haskell, William L.; McConnell, Michael V.; Carstensen, Laura L.

2015-01-01

Getting enough sleep, exercising and limiting sedentary activities can greatly contribute to disease prevention and overall health and longevity. Measuring the full 24-hour activity cycle - sleep, sedentary behavior (SED), light intensity physical activity (LPA) and moderate-to-vigorous physical activity (MVPA) - may now be feasible using small wearable devices. PURPOSE This study compares nine devices for accuracy in 24-hour activity measurement. METHODS Adults (N=40, 47% male) wore nine devices for 24-hours: Actigraph GT3X+, activPAL, Fitbit One, GENEactiv, Jawbone Up, LUMOback, Nike Fuelband, Omron pedometer, and Z-Machine. Comparisons (to standards) were made for total sleep time (Z-machine), time spent in SED (activPAL), LPA (GT3x+), MVPA (GT3x+), and steps (Omron). Analysis included mean absolute percent error, equivalence testing, and Bland-Altman plots. RESULTS Error rates ranged from 8.1–16.9% for sleep; 9.5–65.8% for SED; 19.7–28.0% for LPA; 51.8–92% for MVPA; and 14.1–29.9% for steps. Equivalence testing indicated only two comparisons were significantly equivalent to standards: the LUMOback for sedentary behavior and the GT3X+ for sleep. Bland-Altman plots indicated GT3X+ had the closest measurement for sleep, LUMOback for sedentary behavior, GENEactiv for LPA, Fitbit for MVPA and GT3X+ for steps. CONCLUSIONS Currently, no device accurately captures activity data across the entire 24-hour day, but the future of activity measurement should aim for accurate 24-hour measurement as a goal. Researchers should continue to select measurement devices based on their primary outcomes of interest. PMID:26484953

24-Hour Blood Pressure Variability Assessed by Average Real Variability: A Systematic Review and Meta-Analysis.

Science.gov (United States)

Mena, Luis J; Felix, Vanessa G; Melgarejo, Jesus D; Maestre, Gladys E

2017-10-19

Although 24-hour blood pressure (BP) variability (BPV) is predictive of cardiovascular outcomes independent of absolute BP levels, it is not regularly assessed in clinical practice. One possible limitation to routine BPV assessment is the lack of standardized methods for accurately estimating 24-hour BPV. We conducted a systematic review to assess the predictive power of reported BPV indexes to address appropriate quantification of 24-hour BPV, including the average real variability (ARV) index. Studies chosen for review were those that presented data for 24-hour BPV in adults from meta-analysis, longitudinal or cross-sectional design, and examined BPV in terms of the following issues: (1) methods used to calculate and evaluate ARV; (2) assessment of 24-hour BPV determined using noninvasive ambulatory BP monitoring; (3) multivariate analysis adjusted for covariates, including some measure of BP; (4) association of 24-hour BPV with subclinical organ damage; and (5) the predictive value of 24-hour BPV on target organ damage and rate of cardiovascular events. Of the 19 assessed studies, 17 reported significant associations between high ARV and the presence and progression of subclinical organ damage, as well as the incidence of hard end points, such as cardiovascular events. In all these cases, ARV remained a significant independent predictor ( P <0.05) after adjustment for BP and other clinical factors. In addition, increased ARV in systolic BP was associated with risk of all cardiovascular events (hazard ratio, 1.18; 95% confidence interval, 1.09-1.27). Only 2 cross-sectional studies did not find that high ARV was a significant risk factor. Current evidence suggests that ARV index adds significant prognostic information to 24-hour ambulatory BP monitoring and is a useful approach for studying the clinical value of BPV. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Detection of myocardial viability by means of Single Proton Emission Computed Tomography (Perfused SPECT) dual {sup 201} Tl (rest of 15 minutes, 24 late hours and 24 hours reinjection) and gated-SPECT {sup 99m} Tc-SESTAMIBI in effort or stimulation of the coronary reserves; Deteccion de viabilidad miocardica mediante tomografia por emision de foton unico (SPECT perfusorio) dual {sup 201} Talio (Reposo de 15 minutos, 24 horas tardio y 24 horas reinyeccion) y gated-SPECT {sup 99m} Tc-SESTAMIBI en esfuerzo o estimulo de reserva coronaria

Energy Technology Data Exchange (ETDEWEB)

Mendoza V, R

2004-07-01

The objective of this work was to determine if the images of SPECT {sup 201} TI in rest of 15 minutes, 24 late hours and Gated-SPECT {sup 99m} Tc-SESTAMIBI in effort or stimulation of coronary reservation correlate with the study of 24 hours post reinjection of {sup 201}TI to determine the presence of having knitted viable myocardium. Material and methods: 29 patients were studied with coronary arterial illness (EAC) to who are carried out SPECT {sup 201} TI in rest with images of 15 minutes, 24 late hours and 24 hours reinjection, by means of the administration of {sup 201}TI to dose of 130 MBq and reinjection with 37 MBq. and Gated-SPECT {sup 99m}Tc-SESTAMIBI in effort or stimulation of coronary reservation, later to the administration of 1110 MBq. Results: 29 patients were included according to inclusion approaches and exclusion, of those which 22 (75.86%) they correspond at the masculine sex and 7 (24.13%) to the feminine one, with an average of 62.1 year-old age, 2320 segments myocardial were analysed so much it is phase post-effort as rest; they were diagnosed a total of 264 segments with heart attack, of which viability myocardium was observed in 174 segments. The statistical tests are analysis of frequencies. The non parametric test of Wilcoxon and Mann-Whitney. Conclusions: the viability myocardial at the 24 late hours and 24 hours reinjection was similar; significant difference exists between the study of 15 minutes and 24 hours reinjection, ischemic illness was also demonstrated in territories different to the heart attack area in the studies of 15 minutes, late 24 hours and 24 hours reinjection. (Author)

Weekly 24-hour continuous infusion interleukin-2 for metastatic melanoma and renal cell carcinoma: a phase I study.

Science.gov (United States)

Perez, E A; Scudder, S A; Meyers, F A; Tanaka, M S; Paradise, C; Gandara, D R

1991-02-01

Twenty-nine patients with biopsy-confirmed metastatic melanoma (17) or metastatic renal cell carcinoma (12) were treated with escalating doses or recombinant human interleukin-2 (IL-2) administered as weekly 24-h intravenous infusions. Patients received from 3 to 12 x 10(6) C.U./m2 (18-72 x 10(6) I.U./m2) weekly over a treatment period of 1 to 16 weeks, with a median of eight weekly cycles administered. Patients in all treatment groups experienced non-life-threatening systemic side effects consisting of fever, nausea, vomiting, fluid retention, and diarrhea. Grade III hypotension was seen in four of six patients (67%) at 12 x 10(6) C.U./m2, and represented the dose-limiting toxicity. Grade IV hypotension occurred in 1 of 14 patients at 6 x 10(6) C.U./m2; no other grade IV toxicities were observed. Grade III fever occurred in 3 of 11 patients (27%) treated at 3 x 10(6) C.U./m2, 3 of 14 patients (21%) at 6 x 10(6) C.U./m2, and 3 of 6 patients (50%) at 9 x 10(6) C.U./m2. An objective response was observed in 3 of 28 evaluable patients (10%): 1 complete response and 1 partial response in renal cell cancer, and 1 partial response in a melanoma patient. We conclude that for future studies, the recommended dose of IL-2 given as a weekly 24-h infusion is 9 x 10(6) C.U./m2 and that a low rate of objective tumor response can be obtained in patients with melanoma and renal cell carcinoma using this regimen.

24-Hour Holter Monitoring at the Lagos State University Teaching ...

African Journals Online (AJOL)

However, only a minority of such patients have documented and confirmed clinically significant tachyarrhythmias in this study. A subsequent larger prospective study would shed more light on this subject. Key Words: Electrocardiogram (ECG), 24-hour Holter, Heart Rate variability. Paroxysmal tachyarrhythmias.

Safety, adherence and acceptability of intermittent tenofovir/emtricitabine as HIV pre-exposure prophylaxis (PrEP among HIV-uninfected Ugandan volunteers living in HIV-serodiscordant relationships: a randomized, clinical trial.

Directory of Open Access Journals (Sweden)

Freddie M Kibengo

Full Text Available BACKGROUND: Efficacy of oral pre-exposure prophylaxis (PrEP in prevention of HIV acquisition has been evaluated using a daily regimen. However, adherence to long term daily medication is rarely perfect. Intermittent regimen may be a feasible alternative. Preclinical studies have demonstrated effectiveness of intermittent PrEP in SHIV prevention among animals. However, little is known about intermittent PrEP regimens. DESIGN: Seventy two HIV-uninfected volunteers in HIV serodiscordant couple relationships in Uganda were randomly assigned to receive daily oral Tenofovir/Emtricitabine (TDF/FTC-Truvada or placebo, or intermittent (Monday, Friday and within 2 hours after sex, not to exceed one dose per day oral TDF/FTC or placebo in a 2:1:2:1 ratio. Volunteers and study staff were blinded to drug assignment, but not to regimen assignment. METHODS: Volunteers were followed for 4 months after randomization, with monthly clinical and laboratory safety assessments and comprehensive HIV risk reduction services. Adherence was monitored using medication event monitoring system (MEMS and self-report. Sexual activity data were collected via daily short text message (SMS and self-report. HIV-specific immune responses were assessed by IFN-γ ELISPOT. RESULTS: Both daily and intermittent oral TDF/FTC regimens were well tolerated. Median MEMS adherence rates were 98% (IQR: 93-100 for daily PrEP regimen, 91% (IQR: 73-97 for fixed intermittent dosing and 45% (IQR: 20-63 for post-coital dosing. SMS response rate was 74%, but increased to 80% after excluding server outages; results may have been affected by the novelty of this measure. The majority of volunteers expressed willingness with no particular preference for either regimen. CONCLUSIONS: Both daily and intermittent oral PrEP dosing regimens were safe. Adherence was high for daily and fixed intermittent dosing; post-coital dosing was associated with poor adherence. Fixed intermittent PrEP regimens may be

Gene and protein expression of epidermal growth factor measured on the kidney 24 hours after irradiation correlates to late radiation damage

International Nuclear Information System (INIS)

Otsuka, Makoto; Hatakenaka, Masamitsu

2001-01-01

This study was designed to evaluate the proliferative response of epidermal growth factor (EGF) gene expression as an early indicator of late renal radiation damage. EGF gene expression was measured in the irradiated left kidney of C3H/HeSlc mice using RT-PCR 24 hours after radiation doses of 9, 12, or 15 Gy. In a second experiment, the same radiation doses were administered to the right kidney plus the lower half of the left kidney. The partly irradiated left kidneys were harvested and EGF gene expression was measured. The irradiated whole right kidneys were subjected to immunohistochemical staining for EGF protein. In a third experiment, 12 Gy was administered to the right kidney plus the lower half of the left kidney. The mice underwent left nephrectomy 24 hours after radiation, and the EGF gene expression in the kidney was correlated with the blood urea nitrogen (BUN) level representing late renal functional damage. EGF expression increased in 1 of 10 control mice and in 9 of 10 mice that received 15 Gy. The extent of increase of EGF was dependent on radiation dose. In mice having an increased BUN level after irradiation, 7 of 10 had EGF positive irradiated kidneys. All six mice whose BUN levels were unchanged had EGF-negative irradiated kidneys. EGF protein staining was observed in tubule cells only, not in glomerular cells. The amount of EGF protein staining correlated with radiation dose to some extent. EGF gene expression seems to be a very early indicator of late radiation damage to the kidney. (author)

Regulatory requirements for marketing fixed dose combinations

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B G Jayasheel

2010-01-01

Full Text Available The development of fixed-dose combinations (FDCs is becoming increasingly important from a public health perspective. FDCs have advantages when there is an identifiable patient population for whom treatment with a particular combination of actives in a fixed ratio is safe and effective and when all of the actives contribute to the overall therapeutic effect. Such combinations of drugs are particularly useful in the management of chronic diseases. In addition, there can be real clinical benefits in the form of increased efficacy and/or a reduced incidence of adverse effects. Additional advantages of FDCs are potentially lower costs of manufacturing compared to the costs of producing separate products administered concurrently, simpler logistics of distribution and reduced development of resistance in the case of antimicrobials. Above all, FDC therapy reduces pill burden and improves medication compliance. Although, FDCs seem to be ideal under certain pre-defined circumstances, if a dosing adjustment is warranted, there may not be an FDC available in the most appropriate strength for the patient and if an adverse drug reaction occurs from using an FDC, it may be difficult to identify the active ingredient responsible for causing the reaction. Appendix VI of Schedule Y (Drugs & Cosmetics Rules 1945, India states the requirements for marketing approval of various types of FDCs. The same is further elaborated in this article to provide a detailed guidance including the clinical trial requirements. However, the heterogeneity of the therapeutic field makes it difficult to develop a standard guidance document.

Skin dose differences between intensity-modulated radiation therapy and volumetric-modulated arc therapy and between boost and integrated treatment regimens for treating head and neck and other cancer sites in patients

International Nuclear Information System (INIS)

Penoncello, Gregory P.; Ding, George X.

2016-01-01

The purpose of this study was (1) to evaluate dose to skin between volumetric-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT) treatment techniques for target sites in the head and neck, pelvis, and brain and (2) to determine if the treatment dose and fractionation regimen affect the skin dose between traditional sequential boost and integrated boost regimens for patients with head and neck cancer. A total of 19 patients and 48 plans were evaluated. The Eclipse (v11) treatment planning system was used to plan therapy in 9 patients with head and neck cancer, 5 patients with prostate cancer, and 5 patients with brain cancer with VMAT and static-field IMRT. The mean skin dose and the maximum dose to a contiguous volume of 2 cm"3 for head and neck plans and brain plans and a contiguous volume of 5 cm"3 for pelvis plans were compared for each treatment technique. Of the 9 patients with head and neck cancer, 3 underwent an integrated boost regimen. One integrated boost plan was replanned with IMRT and VMAT using a traditional boost regimen. For target sites located in the head and neck, VMAT reduced the mean dose and contiguous hot spot most noticeably in the shoulder region by 5.6% and 5.4%, respectively. When using an integrated boost regimen, the contiguous hot spot skin dose in the shoulder was larger on average than a traditional boost pattern by 26.5% and the mean skin dose was larger by 1.7%. VMAT techniques largely decrease the contiguous hot spot in the skin in the pelvis by an average of 36% compared with IMRT. For the same target coverage, VMAT can reduce the skin dose in all the regions of the body, but more noticeably in the shoulders in patients with head and neck and pelvis cancer. We also found that using integrated boost regimens in patients with head and neck cancer leads to higher shoulder skin doses compared with traditional boost regimens.

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

Science.gov (United States)

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

2017-03-15

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

Occurrence of hypotension in older participants. Which 24-hour ABPM parameter better correlate with?

Science.gov (United States)

Scuteri, Angelo; Modestino, Anna; Frattari, Alessandra; Di Daniele, Nicola; Tesauro, Manfredi

2012-06-01

The aim of the present study was to investigate the prevalence of hypotension in older participants and to identify which 24-hour ambulatory blood pressure monitoring parameter better correlated with the occurrence of hypotension. We studied 588 elderly participants (mean age 78.7 ± 7.1 years; 70% women) who underwent a 24-hour ambulatory blood pressure (BP) monitoring, without moderate-to-severe cognitive impairment, myocardial infarction, or stroke within the previous 6 months; renal (serum creatinine > 2.5 mg/dL), respiratory, or liver insufficiency; and atrial fibrillation. In older participants, the occurrence of systolic hypotension is very common (≈55% presenting at least one episode of systolic blood pressure (SBP) < 100 mmHg and about 20% presenting ≥10% of the SBP registrations < 100 mmHg). More than 30% of participants with 24-hour SBP, daytime, and nighttime above the reference threshold had hypotension. Hypotension did not correlated with BP variability indices (standard deviation of BPs). None of the parameters commonly present in 24-hour ambulatory BP monitoring clinical reports is able to accurately identify those older participants with episode of hypotension. Episodes of SBP hypotension are extremely common in older participants and do not appear to relate to BP variability indices. Indeed, no parameter of 24-hour ambulatory BP monitoring was capable to accurately identify the occurrence of hypotension. We expect that ongoing studies will contribute to identification of specific factors predicting hypotensive episodes in the older participants.

Feasibility of ambulatory, continuous 24-hour finger arterial pressure recording

NARCIS (Netherlands)

Imholz, B. P.; Langewouters, G. J.; van Montfrans, G. A.; Parati, G.; van Goudoever, J.; Wesseling, K. H.; Wieling, W.; Mancia, G.

1993-01-01

We tested Portapres, an innovative portable, battery-operated device for the continuous, noninvasive, 24-hour ambulatory measurement of blood pressure in the finger. Portapres is based on Finapres, a stationary device for the measurement of finger arterial pressure. Systems were added to record

Comparison of an Additional Transdermal Fentanyl Patch Compared to Intravenous NSAID and Opioid Analgesics within 24 Hours of an Uterine Artery Embolization for Myoma and Adenomyosis

Energy Technology Data Exchange (ETDEWEB)

Song, Suk Yun; Kang, Byung Chul; Rho, Kyung Min [Dept. of Radiology, Mokdong Hospital, Ewha Womans University School of Medicine, Seoul (Korea, Republic of)

2011-05-15

To evaluate the effectiveness of an additional transdermal fentanyl patch compared to intravenous analgesics in pain control during the 24-hour period following uterine artery embolization (UAE) for myoma and adenomyosis. Between September 2009 and August 2010, 42 patients underwent UAE for myoma or adenomyosis. Of these, 21 received an intravenous opioid (pethidine) and a nonsteroidal anti-inflammatory drug (group A), and 21 received an additional transdermal fentanyl patch (group B). Pain perception levels were established verbally on a 0-10 scale during the 24-hour period following UAE. Differences in pain trends, mean dose of intravenous pethidine, and adverse effects were compared between the two groups. Pain perception was most severe at 6 hours after UAE and the mean pain level of group B at that time was 6.3 {+-} 0.7, which was significantly lower than that of group A, 8.2 {+-} 0.7 (p<0.05). The mean dose of intravenous pethidine was 114.3 {+-} 59.5 mg in group A and 90.5 {+-} 49.0 mg in group B, while the incidence of nausea was 67% in group A and 77% in group B. In both cases, the differences were not significantly different (p>0.05), and no evidence of respiratory distress was demonstrated. The addition of a transdermal fentanyl patch to intravenous analgesics is effective in reducing post-embolization pain during the 24-hour period after UAE.

24-Hour Fetal/Maternal Monitoring System Based on Phonocardiogram Analysis

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Zhdanov Dmitry

2018-01-01

Full Text Available The article describes an engineering prototype of the Device for 24-hour monitoring over the functional state of the fetus and mother’s cardiovascular system in the antenatal period of pregnancy. The Device is a hardware and software system that ensures the registration and analysis of fetus and mother’s phonocardiograms with further processing and interpretation. The interpretation process is designed to timely detect conditions that constitute a threat to a fetus. The Device operates as part of a telemedicine network that allows obstetricians-gynecologists managing pregnant women to remotely control their state. The article describes the Device design concept and features of its specific components. The engineering prototype of the Device was used to carry out biomedical tests that confirmed its suitability for 24-hour monitoring over the functional state of fetus and mother’s cardiovascular system in home settings.

TH-302, a hypoxia-activated prodrug with broad in vivo preclinical combination therapy efficacy: optimization of dosing regimens and schedules.

Science.gov (United States)

Liu, Qian; Sun, Jessica D; Wang, Jingli; Ahluwalia, Dharmendra; Baker, Amanda F; Cranmer, Lee D; Ferraro, Damien; Wang, Yan; Duan, Jian-Xin; Ammons, W Steve; Curd, John G; Matteucci, Mark D; Hart, Charles P

2012-06-01

Subregional hypoxia is a common feature of tumors and is recognized as a limiting factor for the success of radiotherapy and chemotherapy. TH-302, a hypoxia-activated prodrug selectively targeting hypoxic regions of solid tumors, delivers a cytotoxic warhead to the tumor, while maintaining relatively low systemic toxicity. The antitumor activity, different dosing sequences, and dosing regimens of TH-302 in combination with commonly used conventional chemotherapeutics were investigated in human tumor xenograft models. Seven chemotherapeutic drugs (docetaxel, cisplatin, pemetrexed, irinotecan, doxorubicin, gemcitabine, and temozolomide) were tested in combination with TH-302 in eleven human xenograft models, including non-small cell lung cancer (NSCLC), colon cancer, prostate cancer, fibrosarcoma, melanoma, and pancreatic cancer. The antitumor activity of docetaxel, cisplatin, pemetrexed, irinotecan, doxorubicin, gemcitabine, and temozolomide was increased when combined with TH-302 in nine out of eleven models tested. Administration of TH-302 2-8 h prior to the other chemotherapeutics yielded superior efficacy versus other sequences tested. Simultaneous administration of TH-302 and chemotherapeutics increased toxicity versus schedules with dosing separations. In a dosing optimization study, TH-302 administered daily at 50 mg/kg intraperitoneally for 5 days per week in the H460 NSCLC model showed the optimal response with minimal toxicity. TH-302 enhances the activity of a wide range of conventional anti-neoplastic agents in a broad panel of in vivo xenograft models. These data highlight in vivo effects of schedule and order of drug administration in regimen efficacy and toxicity and have relevance to the design of human regimens incorporating TH-302.

Preventive effects of lansoprazole and famotidine on gastric mucosal injury induced by low-dose aspirin in Helicobacter pylori-negative healthy volunteers.

Science.gov (United States)

Nishino, Masafumi; Sugimoto, Mitsushige; Kodaira, Chise; Yamade, Mihoko; Uotani, Takahiro; Shirai, Naohito; Ikuma, Mutsuhiro; Tanaka, Tatsuo; Sugimura, Haruhiko; Hishida, Akira; Furuta, Takahisa

2011-07-01

The preventive effects of lansoprazole and famotidine on low-dose aspirin-induced gastric mucosal injury in relation to gastric acidity were compared in healthy Japanese volunteers. Fifteen Helicobacter pylori-negative volunteers with different CYP2C19 genotypes were randomly administered aspirin 100 mg, aspirin plus famotidine 20 mg twice daily, or aspirin plus lansoprazole 15 mg once daily for 7 days each in a crossover fashion. Gastroscopy for the evaluation of mucosal injury based on modified Lanza score (MLS) and 24-hour intragastric pH monitoring were performed on day 7 of each regimen. Aspirin induced gastric mucosal injury (median MLS = 3). Lansoprazole significantly decreased MLS to 0, which was significantly lower than that by famotidine (MLS = 1) (P lansoprazole regimen were significantly higher than those with famotidine (P lansoprazole appeared to be more protective than famotidine against low-dose aspirin-induced mucosal injury but a larger well-controlled study is necessary to establish a definitive clinical benefit.

Intermittent Dosing of Micafungin Is Effective for Treatment of Experimental Disseminated Candidiasis in Persistently Neutropenic Rabbits.

Science.gov (United States)

Petraitiene, Ruta; Petraitis, Vidmantas; Hope, William W; Walsh, Thomas J

2015-12-01

The current standard of treatment of invasive candidiasis with echinocandins requires once-daily therapy. To improve quality of life, reduce costs, and improve outcome, we studied the pharmacokinetics (PK), efficacy, and safety of alternate dosing regimens of micafungin (MFG) for the treatment of experimental subacute disseminated candidiasis. MFG was administered for 12 days starting 24 hours after intravenous inoculation of 1 × 10(3) Candida albicans blastoconidia. Study groups consisted of MFG at 1 mg/kg every 24 hours (MFG1), 2 mg/kg every 48 hours (MFG2), and 3 mg/kg every 72 hours (MFG3), and untreated controls. PK of MFG were determined on day 7 by high-performance liquid chromatography and modeled using nonparametric adaptive grid program. A 2-compartment PK model with volume of the central compartment (Vc), clearance (SCL), and the intercompartmental rate constants Kcp and Kpc was used. The fungal burden in 7 tissues was determined 312 hours after the initiation of therapy. PK of MFG were linear and the parameter means ± SD were Vc = 0.41 ± 0.18 L, Kcp = 2.80 ± 1.55/hour, Kpc = 1.71 ± 0.93/hour, and SCL = 0.16 ± 0.003 L/hour (r(2) = 0.99). The area under the plasma drug concentration - time curve for MFG1, MFG2, and MFG3 was 198.7 ± 19.8, 166.3 ± 36.7, and 192.8 ± 46.2 mg × hour/L, respectively (P = .24). All treatment groups showed significant and comparable resolution of (1→3)-β-D-glucan levels and clearance of C. albicans from liver, spleen, kidney, brain, lung, vitreous humor, and vena cava in comparison to untreated controls (P ≤ .05). There were no differences in hepatic or renal function among study groups. Less fractionated MFG regimens of every 48 and 72 hours are safe and as effective in experimental disseminated candidiasis as once-daily therapy in neutropenic hosts. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e

Impact of Different Normality Thresholds for 24-hour ABPM at the Primary Health Care Level

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Guilherme Brasil Grezzana

Full Text Available Abstract Background: Hypertension is an important risk factor for cardiovascular outcomes. Primary health care (PHC physicians should be prepared to act appropriately in the prevention of cardiovascular risk factors. However, the rates of patients with control of blood pressure (BP remain low. The impact of the reclassification of high BP by 24-hour ambulatory BP monitoring (ABPM can lead to different medical decisions in PHC. Objective: To evaluate the agreement between the BP measured by a conventional method by PHC physicians and by 24-hour ABPM, considering different BP normal thresholds for the 24-hour ABPM according to the V Brazilian ABPM Guidelines and the European Society of Hypertension Guidelines. Methods: A cross-sectional study including 569 hypertensive patients. The BP was initially measured by the PHC physicians and, later, by 24-hour ABPM. The BP measurements were obtained independently between the two methods. The therapeutic targets for the conventional BP followed the guidelines by the Eighth Joint National Committee (JNC 8, the V ABPM Brazilian Guidelines, and the 2013 European Hypertension Guidelines. Results: There was an accuracy of 54.8% (95% confidence interval [95%CI] 0.51 - 0.58% for the BP measured with the conventional method when compared with the 24-hour ABPM, with a sensitivity of 85% (95%CI 80.8 - 88.6%, specificity of 31.9% (95%CI 28.7 - 34.7%, and kappa value of 0.155, when considering the European Hypertension Guidelines. When using more stringent thresholds to characterize the BP as "normal" by ABPM, the accuracy was 45% (95%CI 0.41 - 0.47% for conventional measurement when compared with 24-hour ABPM, with a sensitivity of 86.7% (95%CI 0.81 - 0.91%, specificity of 29% (95%CI 0.26 - 0.30%, and kappa value of 0.103. Conclusion: The BP measurements obtained by PHC physicians showed low accuracy when compared with those obtained by 24-hour ABPM, regardless of the threshold set by the different guidelines.

Design of simple UV Spectrophotometric and HPLC methods for assay of artesunate and amodiaquine in fixed dose tablet formulations

International Nuclear Information System (INIS)

Ashie, Agatha Dei

2013-07-01

Artesunate and Amodiaquine combination is one of the first line drugs for the treatment of uncomplicated malaria. To prevent treatment failures and emergence of resistant strains of the Plasmodium parasite, patients are entreated to comply with treatment regimens. Thus fixed dose tablet formulations came as a relieve to patients, ensuring proper compliance as the number of tablets to be taken was reduced. It is therefore important to develop simple methods of assay for these formulations to ensure that quality drugs are available and to prevent resistance to these drugs. This thesis describes Ultraviolet (UV) and High Performance Liquid Chromatographic (HPLC) methods of assay for Artesunate (AS) and Amodiaduine Hydrochloride (AMQ) in fixed dose tablet formulations. The UV absorption spectroscopy was used to establish a wavelength of maximum absorption and the Beer’s plot generated. At 339nm, Amodiaquine Hydrochloride was assayed accurately in methanol with a high r"2 value of 0.998, an intra and inter day precision of Relative Standard Deviation (RSD) of 1.52% and 1.86% respectively. The Beer’s plot was obeyed in a concentration range of 3.5 - 24.8(µg/mL). The limit of detection and limit of quantification was 1.23(µg/mL) and 3.73(µg/mL) respectively. However the UV method could not be used to assay AS simultaneously with AMQ. A mobile phase of 60% acetonitrile and 40% of 0.05% trifluoroacetic acid, flow rate of 1ml/min, wavelength of detection of 225nm and a C_1_8 stationary phase are the parameters for the HPLC method. The r"2 for the HPLC method was 0.996 and 0.995 for Amodiaquine hydrochloride and Artesunate respectively. The intra and inter day precision were 1.07% and 1.42% respectively. The limit of detection and limit of quantification were 0.015%w/v and 0.0465%w/v for Amodiaquine hydrochloride and 0.054%w/v and 0.019%w/v for Artesunate respectively. The concentration ranges were 0.01 - 0.16%w/v for Amodiaquine hydrochloride and 0.01 – 0.2%w/v for

Comparison of an Additional Transdermal Fentanyl Patch Compared to Intravenous NSAID and Opioid Analgesics within 24 Hours of an Uterine Artery Embolization for Myoma and Adenomyosis

International Nuclear Information System (INIS)

Song, Suk Yun; Kang, Byung Chul; Rho, Kyung Min

2011-01-01

To evaluate the effectiveness of an additional transdermal fentanyl patch compared to intravenous analgesics in pain control during the 24-hour period following uterine artery embolization (UAE) for myoma and adenomyosis. Between September 2009 and August 2010, 42 patients underwent UAE for myoma or adenomyosis. Of these, 21 received an intravenous opioid (pethidine) and a nonsteroidal anti-inflammatory drug (group A), and 21 received an additional transdermal fentanyl patch (group B). Pain perception levels were established verbally on a 0-10 scale during the 24-hour period following UAE. Differences in pain trends, mean dose of intravenous pethidine, and adverse effects were compared between the two groups. Pain perception was most severe at 6 hours after UAE and the mean pain level of group B at that time was 6.3 ± 0.7, which was significantly lower than that of group A, 8.2 ± 0.7 (p 0.05), and no evidence of respiratory distress was demonstrated. The addition of a transdermal fentanyl patch to intravenous analgesics is effective in reducing post-embolization pain during the 24-hour period after UAE.

Comparison of the Efficacy and Safety of 2 Acetaminophen Dosing Regimens in Febrile Infants and Children: A Report on 3 Legacy Studies.

Science.gov (United States)

Temple, Anthony R; Zimmerman, Brenda; Gelotte, Cathy; Kuffner, Edwin K

2017-01-01

Compare efficacy and safety of 10 to 15 mg/kg with 20 to 30 mg/kg acetaminophen in febrile children 6 months to ≤ 11 years from 3 double-blind, randomized, single or multiple dose studies. Doses were compared on sum of the temperature differences (SUMDIFF), maximum temperature difference (MAXDIFF), temperature differences at each time point, and dose by time interactions. Alanine aminotransferase (ALT) was evaluated in the 72-hour duration study. A single dose of acetaminophen 20 to 30 mg/kg produced a greater effect on temperature decrement and duration of antipyretic effect over 8 hours than a single dose of 10 to 15 mg/kg. When equivalent total doses (i.e., 2 doses of 10 to 15 mg/kg given at 4-hour intervals and 1 dose of 20 to 30 mg/kg) were given over the initial 8-hour period, there were no significant temperature differences. Over a 72-hour period, 10 to 15 mg/kg acetaminophen administered every 4 hours maintained a more consistent temperature decrement than 20 to 30 mg/kg acetaminophen administered every 8 hours. Following doses of 60 to 90 mg/kg/day for up to 72 hours, no child had a clinically important increase in ALT from baseline. The number of children with reported adverse events was similar between doses. Data demonstrate the antipyretic effect of acetaminophen is dependent on total dose over a given time interval. These 3 studies provide clinical evidence that the recommended standard acetaminophen dose of 10 to 15 mg/kg is a safe and effective dose for treating fever in pediatric patients when administered as a single dose or as multiple doses for up to 72 hours.

4. Evaluation of the quality of fixed dose combination anti ...

African Journals Online (AJOL)

Esem

Methodology: This was a cross sectional study whose objective was to determine the quality of 3 types of fixed dose combination (FDC) anti TB drugs namely 4FDC, 3FDC and 2FDC tablets available in Lusaka District by assessing the presence of active ingredients and the percentage content of these active ingredients ...

A COMPARATIVE STUDY OF PREEMPTIVE USE OF 0.2% ROPIVACAINE AND 0.125% BUPIVACAINE ALONG WITH FENTANYL AND FENTANYL INCREMENTS TO PROVIDE POSTOPERATIVE EPIDURAL ANALGESIA UP TO 24 HOURS

Directory of Open Access Journals (Sweden)

Chiranji Lal Khedia

2016-06-01

Full Text Available BACKGROUND AND OBJECTIVES The present study was carried out to compare duration of analgesia, haemodynamic changes (Systolic and Diastolic Blood Pressure, Pulse Rate, Respiratory Rate, total incremental doses of epidural fentanyl required to maintain VAS 3 up to 24 hours in each group and total required incremental fentanyl doses were compared between both the groups. Once the data were collected from all the patients, they were compared using, chi-square test, two sample t-test. The p-value was calculated and P <0.05 was considered statistically significant. RESULTS The duration of analgesia was more with Group BF (245+17.58 min. than Group RF (217.6+22.41 min., thus it is concluded that difference in duration of analgesia was statistically significant between the groups (P<0.05. In this study, it was noticed that patients of Group RF required much more incremental doses of epidural fentanyl (218+31.88 μg to maintain VAS<3 up to 24 hours than group BF (170+32.27 μg, and difference was statistically significant (P<0.05. Haemodynamic parameters like SBP, DBP, HR and RR were comparable in both the groups. Hypotension and bradycardia were noted in two patients of group BF. CONCLUSION Duration of analgesia was longer and comparatively better in group BF and less incremental doses were required to maintain VAS <3 up to 24 hours as compared to group RF, but haemodynamic stability was more in group RF as compared to group BF.

Skin dose differences between intensity-modulated radiation therapy and volumetric-modulated arc therapy and between boost and integrated treatment regimens for treating head and neck and other cancer sites in patients.

Science.gov (United States)

Penoncello, Gregory P; Ding, George X

2016-01-01

The purpose of this study was (1) to evaluate dose to skin between volumetric-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT) treatment techniques for target sites in the head and neck, pelvis, and brain and (2) to determine if the treatment dose and fractionation regimen affect the skin dose between traditional sequential boost and integrated boost regimens for patients with head and neck cancer. A total of 19 patients and 48 plans were evaluated. The Eclipse (v11) treatment planning system was used to plan therapy in 9 patients with head and neck cancer, 5 patients with prostate cancer, and 5 patients with brain cancer with VMAT and static-field IMRT. The mean skin dose and the maximum dose to a contiguous volume of 2cm(3) for head and neck plans and brain plans and a contiguous volume of 5cm(3) for pelvis plans were compared for each treatment technique. Of the 9 patients with head and neck cancer, 3 underwent an integrated boost regimen. One integrated boost plan was replanned with IMRT and VMAT using a traditional boost regimen. For target sites located in the head and neck, VMAT reduced the mean dose and contiguous hot spot most noticeably in the shoulder region by 5.6% and 5.4%, respectively. When using an integrated boost regimen, the contiguous hot spot skin dose in the shoulder was larger on average than a traditional boost pattern by 26.5% and the mean skin dose was larger by 1.7%. VMAT techniques largely decrease the contiguous hot spot in the skin in the pelvis by an average of 36% compared with IMRT. For the same target coverage, VMAT can reduce the skin dose in all the regions of the body, but more noticeably in the shoulders in patients with head and neck and pelvis cancer. We also found that using integrated boost regimens in patients with head and neck cancer leads to higher shoulder skin doses compared with traditional boost regimens. Copyright © 2016 American Association of Medical Dosimetrists. Published by

Determination of maximum physiologic thyroid uptake and correlation with 24-hour RAI uptake value

International Nuclear Information System (INIS)

Duldulao, M.; Obaldo, J.

2007-01-01

Full text: In hyperthyroid patients, thyroid uptake values are overestimated, sometimes approaching or exceeding 100%. This is physiologically and mathematically impossible. This study was undertaken to determine the maximum physiologic thyroid uptake value through a proposed simple method using a gamma camera. Methodology: Twenty-two patients (17 females and 5 males), with ages ranging from 19-61 y/o (mean age ± SD; 41 ± 12), with 24-hour uptake value of >50%, clinically hyperthyroid and referred for subsequent radioactive iodine therapy were studied. The computed maximum physiologic thyroid uptake was compared with the 24-hour uptake using the paired Student t-test and evaluated using linear regression analysis. Results: The computed physiologic uptake correlated poorly with the 24-hour uptake value. However, in the male subgroup, there was no statistically significant difference between the two (p=0.77). Linear regression analysis gives the following relationship: physiologic uptake (%) = 77.76 - 0.284 (24-hour RAI uptake value). Conclusion: Provided that proper regions of interest are applied with correct attenuation and background subtraction, determination of physiologic thyroid uptake may be obtained using the proposed method. This simple method may be useful prior to I-131 therapy for hyperthyroidism especially when a single uptake determination is performed. (author)

Medical Decisions of Pediatric Residents Turn Riskier after a 24-Hour Call with No Sleep.

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Aran, Adi; Wasserteil, Netanel; Gross, Itai; Mendlovic, Joseph; Pollak, Yehuda

2017-01-01

Despite a gradual reduction in the workload during residency, 24-hour calls are still an integral part of most training programs. While sleep deprivation increases the risk propensity, the impact on medical risk taking has not been studied. This study aimed to assess the clinical decision making and psychomotor performance of pediatric residents following a limited nap time during a 24-hour call. A neurocognitive battery (IntegNeuro) and a medical decision questionnaire were completed by 44 pediatric residents at 2 time points: after a 24-hour call and following 3 nights with no calls (sleep ≥5 hours). To monitor sleep, residents wore actigraphs and completed sleep logs. Nap time during the shift was change in risk taking) or 2 to 3 hours (4% decreased risk taking) (difference between groups, P = 0.001). Risk-taking tendency inversely correlated with sustained attention scores (Pearson = -0.433, P = 0.003). Sustained attention was the neurocognitive domain most affected by sleep deprivation (effect size = 0.29, P = 0.025). This study suggests that residents napping less than an hour during a night shift are prone to riskier clinical decisions. Hence, enabling residents to nap at least 1 hour during shifts is recommended. © The Author(s) 2016.

Impact of Drug Therapy, Radiation Dose, and Dose Rate on Renal Toxicity Following Bone Marrow Transplantation

International Nuclear Information System (INIS)

Cheng, Jonathan C.; Schultheiss, Timothy E.; Wong, Jeffrey Y.C.

2008-01-01

Purpose: To demonstrate a radiation dose response and to determine the dosimetric and chemotherapeutic factors that influence the incidence of late renal toxicity following total body irradiation (TBI). Methods and Materials: A comprehensive retrospective review was performed of articles reporting late renal toxicity, along with renal dose, fractionation, dose rate, chemotherapy regimens, and potential nephrotoxic agents. In the final analysis, 12 articles (n = 1,108 patients), consisting of 24 distinct TBI/chemotherapy conditioning regimens were included. Regimens were divided into three subgroups: adults (age ≥18 years), children (age <18 years), and mixed population (both adults and children). Multivariate logistic regression was performed to identify dosimetric and chemotherapeutic factors significantly associated with late renal complications. Results: Individual analysis was performed on each population subgroup. For the purely adult population, the only significant variable was total dose. For the mixed population, the significant variables included total dose, dose rate, and the use of fludarabine. For the pediatric population, only the use of cyclosporin or teniposide was significant; no dose response was noted. A logistic model was generated with the exclusion of the pediatric population because of its lack of dose response. This model yielded the following significant variables: total dose, dose rate, and number of fractions. Conclusion: A dose response for renal damage after TBI was identified. Fractionation and low dose rates are factors to consider when delivering TBI to patients undergoing bone marrow transplantation. Drug therapy also has a major impact on kidney function and can modify the dose-response function

Personal best marathon time and longest training run, not anthropometry, predict performance in recreational 24-hour ultrarunners.

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Knechtle, Beat; Knechtle, Patrizia; Rosemann, Thomas; Lepers, Romuald

2011-08-01

In recent studies, a relationship between both low body fat and low thicknesses of selected skinfolds has been demonstrated for running performance of distances from 100 m to the marathon but not in ultramarathon. We investigated the association of anthropometric and training characteristics with race performance in 63 male recreational ultrarunners in a 24-hour run using bi and multivariate analysis. The athletes achieved an average distance of 146.1 (43.1) km. In the bivariate analysis, body mass (r = -0.25), the sum of 9 skinfolds (r = -0.32), the sum of upper body skinfolds (r = -0.34), body fat percentage (r = -0.32), weekly kilometers ran (r = 0.31), longest training session before the 24-hour run (r = 0.56), and personal best marathon time (r = -0.58) were related to race performance. Stepwise multiple regression showed that both the longest training session before the 24-hour run (p = 0.0013) and the personal best marathon time (p = 0.0015) had the best correlation with race performance. Performance in these 24-hour runners may be predicted (r2 = 0.46) by the following equation: Performance in a 24-hour run, km) = 234.7 + 0.481 (longest training session before the 24-hour run, km) - 0.594 (personal best marathon time, minutes). For practical applications, training variables such as volume and intensity were associated with performance but not anthropometric variables. To achieve maximum kilometers in a 24-hour run, recreational ultrarunners should have a personal best marathon time of ∼3 hours 20 minutes and complete a long training run of ∼60 km before the race, whereas anthropometric characteristics such as low body fat or low skinfold thicknesses showed no association with performance.

Projected 24-hour post-dose ocular itching scores post-treatment with olopatadine 0.7% versus 0.2.

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Fidler, Matthew L; Ogundele, Abayomi; Covert, David; Sarangapani, Ramesh

2018-04-21

Olopatadine is an antihistamine and mast cell stabilizer used for treating allergic conjunctivitis. Olopatadine 0.7% has been recently approved for daily dosing in the US, which supersedes the previously approved 0.2% strength. The objective of this analysis was to characterize patients who have better itching relief at 24 h when taking olopatadine 0.7% treatment instead of olopatadine 0.2% (in terms of proportions of responses) and relate this to the severity of baseline itching as an indirect metric of a patient's sensitivity to antihistamines. A differential odds model was developed using data from two conjunctival allergen challenge (CAC) studies to characterize individual-level and population-level response to ocular itching following olopatadine treatment and the data was analyzed retrospectively. This modeling analysis was designed to predict 24 h ocular itching scores and to quantify the differences in 24 h itching relief following treatment with olopatadine 0.2% versus 0.7% in patients with moderate-to-high baseline itching. A one-compartment kinetic-pharmacodynamic E max model was used to determine the effect of olopatadine. Impact of baseline itching severity, vehicle effect and the drug effect on the overall itching scores post-treatment were explicitly incorporated in the model. The model quantified trends observed in the clinical data with regards to both mean scores and the proportions of patients responding to olopatadine treatment. The model predicts a higher proportion of patients in the olopatadine 0.7% versus 0.2% group will experience relief within 24 h. This prediction was confirmed with retrospective clinical data analysis. The number of allergy patients relieved with olopatadine 0.7% increased with higher baseline itching severity scores, when compared to olopatadine 0.2%.

Continuous 24-hour ocular dimensional profile recording in medically treated normal-tension glaucoma

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Lee JWY

2015-01-01

Full Text Available Jacky WY Lee,1,2 Lin Fu,1 Jennifer WH Shum,1 Jonathan CH Chan,3 Jimmy SM Lai1 1Department of Ophthalmology, The University of Hong Kong, Hong Kong; 2Department of Ophthalmology, Caritas Medical Centre, Hong Kong; 3Department of Ophthalmology, Queen Mary Hospital, Hong Kong Purpose: To analyze the 24-hour ocular dimensional profile in normal-tension glaucoma (NTG patients on medical treatment.Methods: Consecutive, medically treated NTG subjects were recruited from a university eye center. Subjects were on a mean of 1.7±0.7 types of antiglaucoma medications and 56.6% were on a prostaglandin analog. A contact lens-based sensor device was worn in one eye of NTG patients to record the intraocular pressure (IOP-related profile for 24 hours, recording the following: variability from mean over 24 hours, nocturnally and diurnally, as well as the number of peaks and troughs diurnally and nocturnally.Results: In 18 NTG subjects, the nocturnal variability around the mean contact lens-based sensor device signal was 48.9% less than the diurnal variability around the mean. The number of peaks was 54.7% less during the nocturnal period than during the diurnal period. The rate of increase in the ocular dimensional profile when going to sleep was significantly greater than the rate of decrease upon waking (P<0.001.Conclusion: In medically treated NTG subjects, there was more variability in the IOP-related pattern during the daytime and there were fewer peaks during sleep. Keywords: intraocular pressure, 24-hour, normal tension glaucoma

Comparison of 24-hour cardiovascular and autonomic function in paraplegia, tetraplegia, and control groups: implications for cardiovascular risk.

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Rosado-Rivera, Dwindally; Radulovic, M; Handrakis, John P; Cirnigliaro, Christopher M; Jensen, A Marley; Kirshblum, Steve; Bauman, William A; Wecht, Jill Maria

2011-01-01

Fluctuations in 24-hour cardiovascular hemodynamics, specifically heart rate (HR) and blood pressure (BP), are thought to reflect autonomic nervous system (ANS) activity. Persons with spinal cord injury (SCI) represent a model of ANS dysfunction, which may affect 24-hour hemodynamics and predispose these individuals to increased cardiovascular disease risk. To determine 24-hour cardiovascular and ANS function among individuals with tetraplegia (n=20; TETRA: C4-C8), high paraplegia (n=10; HP: T2-T5), low paraplegia (n=9; LP: T7-T12), and non-SCI controls (n=10). Twenty-four-hour ANS function was assessed by time domain parameters of heart rate variability (HRV); the standard deviation of the 5-minute average R-R intervals (SDANN; milliseconds/ms), and the root-mean square of the standard deviation of the R-R intervals (rMSSD; ms). Subjects wore 24-hour ambulatory monitors to record HR, HRV, and BP. Mixed analysis of variance (ANOVA) revealed significantly lower 24-hour BP in the tetraplegic group; however, BP did not differ between the HP, LP, and control groups. Mixed ANOVA suggested significantly elevated 24-hour HR in the HP and LP groups compared to the TETRA and control groups (Pcontrol groups (Pcontrol groups (P<0.01). Twenty-four-hour SDANN was significantly increased in the HP group compared to the LP and TETRA groups (P<0.05) and rMSSD was significantly lower in the LP compared to the other three groups (P<0.05). Elevated 24-hour HR in persons with paraplegia, in concert with altered HRV dynamics, may impart significant adverse cardiovascular consequences, which are currently unappreciated.

24-Hour Relativistic Bit Commitment.

Science.gov (United States)

Verbanis, Ephanielle; Martin, Anthony; Houlmann, Raphaël; Boso, Gianluca; Bussières, Félix; Zbinden, Hugo

2016-09-30

Bit commitment is a fundamental cryptographic primitive in which a party wishes to commit a secret bit to another party. Perfect security between mistrustful parties is unfortunately impossible to achieve through the asynchronous exchange of classical and quantum messages. Perfect security can nonetheless be achieved if each party splits into two agents exchanging classical information at times and locations satisfying strict relativistic constraints. A relativistic multiround protocol to achieve this was previously proposed and used to implement a 2-millisecond commitment time. Much longer durations were initially thought to be insecure, but recent theoretical progress showed that this is not so. In this Letter, we report on the implementation of a 24-hour bit commitment solely based on timed high-speed optical communication and fast data processing, with all agents located within the city of Geneva. This duration is more than 6 orders of magnitude longer than before, and we argue that it could be extended to one year and allow much more flexibility on the locations of the agents. Our implementation offers a practical and viable solution for use in applications such as digital signatures, secure voting and honesty-preserving auctions.

Hematopoietic stem cell transplantation with conditioning regimens containing melphalan in pediatric patients with acute lymphoblastic leukemia

International Nuclear Information System (INIS)

Matsuyama, Takaharu; Kato, Koji

2002-01-01

A multicenter comparative study was carried out to investigate the efficacy and safety of hematopoietic stem cell transplantation with conditioning regimens containing melphalan in pediatric patients with acute lymphoblastic leukemia. One hundred twenty three patients at a variety of remission stages were eligible for study participation. Eighty-nine were transplanted with allogeneic grafts and 34 patients with autologous grafts (23 cases with bone marrow and 11 cases with peripheral blood stem cells). Conditioning regimens used were as follows: melphalan and busulfan for 40 patients, melphalan, busulfan and TBI for 44 patients, other regimens for 39 patients. To accelerate engraftment G-CSF (lenograstim) was administered as a 1-hour or 24-hour drip infusion daily at 5 μg/kg from day 5 until hematological recovery. The five year disease free survival (DFS) was 63% for 42 patients at CR1, 41% for 41 patients at CR2 and 33% for 40 patients at other stages. There was no significant difference in the DFS between allogeneic-transplantation and autologous-transplantation in all disease stages. In patients at remission stage for CR1 and CR2, the 5-year DFS by conditioning regimen was 63% for regimen with melphalan and busulfan, 54% for regimen with melphalan, busulfan and TBI and 54% for regimens with melphalan and TBI. There was no significant difference in the DFS between the groups. Serious complications such as renal failure were observed in 11%, veno-occlusive disease in 9%, and interstitial pneumonia in 9%. The most dominating cause of death was relapse in the disease (48% of deaths) which was most commonly observed in autologous transplantation. Contrary to that, treatment related toxic death was the most frequent cause of deaths in allogeneic-transplantation. (author)

Hematopoietic stem cell transplantation with conditioning regimens containing melphalan in pediatric patients with acute lymphoblastic leukemia

Energy Technology Data Exchange (ETDEWEB)

Matsuyama, Takaharu; Kato, Koji [Nagoya First Red Cross Hospital (Japan). Children' s Medical Center; Hanada, Ryoji [Saitama Children' s Medical Center, Iwatsuki (Japan)] [and others

2002-07-01

A multicenter comparative study was carried out to investigate the efficacy and safety of hematopoietic stem cell transplantation with conditioning regimens containing melphalan in pediatric patients with acute lymphoblastic leukemia. One hundred twenty three patients at a variety of remission stages were eligible for study participation. Eighty-nine were transplanted with allogeneic grafts and 34 patients with autologous grafts (23 cases with bone marrow and 11 cases with peripheral blood stem cells). Conditioning regimens used were as follows: melphalan and busulfan for 40 patients, melphalan, busulfan and TBI for 44 patients, other regimens for 39 patients. To accelerate engraftment G-CSF (lenograstim) was administered as a 1-hour or 24-hour drip infusion daily at 5 {mu}g/kg from day 5 until hematological recovery. The five year disease free survival (DFS) was 63% for 42 patients at CR1, 41% for 41 patients at CR2 and 33% for 40 patients at other stages. There was no significant difference in the DFS between allogeneic-transplantation and autologous-transplantation in all disease stages. In patients at remission stage for CR1 and CR2, the 5-year DFS by conditioning regimen was 63% for regimen with melphalan and busulfan, 54% for regimen with melphalan, busulfan and TBI and 54% for regimens with melphalan and TBI. There was no significant difference in the DFS between the groups. Serious complications such as renal failure were observed in 11%, veno-occlusive disease in 9%, and interstitial pneumonia in 9%. The most dominating cause of death was relapse in the disease (48% of deaths) which was most commonly observed in autologous transplantation. Contrary to that, treatment related toxic death was the most frequent cause of deaths in allogeneic-transplantation. (author)

Assessing the Risk of Birth Defects Associated with Exposure to Fixed-Dose Combined Antituberculous Agents during Pregnancy in Rats

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O. Awodele

2012-01-01

Full Text Available Due to the risks of disease progression and transmission to the newborn, treatment of tuberculosis is often pursued during pregnancy and fixed-dose combined antituberculous agents have been found to be beneficial. Unfortunately, there is paucity of data on the safety of the fixed-dose combined antituberculous drugs during pregnancy. This study intends to assess the teratogenic effect of fixed-dose combined antituberculous drugs on the organogenesis stage of fetal development and also investigate the possible roles of vitamin C in modulating the teratogenic effects of these agents on the fetus using animal model. Pregnant rats were divided into 3 groups with 12 animals per group: group 1 received distilled water (10 mL/kg orally; group 2 received 51.4 mg/kg/day of fixed-dose combined antituberculous agents orally; group 3 received 51.4 mg/kg/day of fixed-dose combined antituberculous agents plus vitamin C (10 mg/kg/day orally. Six rats in each group were randomly selected and sacrificed on day 20 by cervical dislocation prior to day 21 of gestation, and the foetuses were harvested through abdominal incision for physical examination. Blood samples were collected from the 1st filial rats of the remaining six animals for biochemical and hematological examination. The liver, kidney, heart, and brain of all the sacrificed animals were used for histopathological examination. There were significant (≤0.05 low birth weights of the foetuses of the animals that were treated with fixed-dose combined antituberculous agents. The haematological parameters also revealed a reduction in the platelets counts and neutrophiles at the first filial generation. Significant (≤0.05 elevations in the levels of aspartate aminotransferase (AST and alkaline phosphatase (ALP in the foetuses of the animals treated with fixed-dose combined antituberculous agents were also observed. However, the combination of vitamin C with fixed-dose combined antituberculous agents

Cluster-randomized non-inferiority trial to compare supplement consumption and adherence to different dosing regimens for antenatal calcium and iron-folic acid supplementation to prevent preeclampsia and anaemia: rationale and design of the Micronutrient Initiative study

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Moshood O. Omotayo

2015-11-01

Full Text Available Background: To prevent pre-eclampsia in populations with insufficient dietary calcium (Ca intake, the World Health Organisation (WHO recommends routine Ca supplementation during antenatal care (ANC. WHO guidelines suggest a complex dosing regimen, requiring as many as 5 pill-taking events per day when combined with iron and folic acid (IFA supplements. Poor adherence may undermine public health effectiveness, so simpler regimens may be preferable. This trial will compare the effect of the WHO-recommended (higher-dose regimen vs. a simpler, lower-dose regimen on supplement consumption and pill-taking behaviours in Kenyan ANC clients. Design and methods: This is a parallel, non-inferiority, cluster-randomized trial; we examined 16 primary care health facilities in Kenya, 1047 pregnant women between 16-30 weeks gestational age. Higher-dose regimen: 1.5 g elemental calcium in 3 separate doses (500 mg Ca/pill and IFA (60 mg Fe + 400 μg folic acid taken with evening dose. Lower-dose regimen: 1.0 g calcium in 2 separate doses (500 mg Ca/pill with IFA taken as above. Measurements: Primary outcome is Ca pills consumed per day, measured by pill counts. Secondary outcomes include IFA pills consumed per day, client knowledge, motivation, social support, and satisfaction, measured at 4 to 10 weeks post-enrolment. Statistical analyses: Unit of randomization is the health-care facility; unit of analysis is individual client. Intent-to-treat analysis will be implemented with multi-level models to account for clustering. Expected public health impact: If pregnant women prescribed lower doses of Ca ingest as many pills as women prescribed the WHO-recommended regimen, developing a lower-dose recommendation for antenatal Ca and IFA supplementation programs could save resources.

The 24- hour pattern of intraocular pressure in suspected glaucoma patients

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Shan-Shan Li

2018-05-01

Full Text Available AIM: To analyze the value of 24-hour intraocular pressure(IOPmonitoring in suspected glaucoma patients.METHODS: Totally 48 suspected glaucoma(96 eyeswere selected for 24-hour IOP monitoring by using Accupen tonometer(24-3000and non-contact tonometer(NCT, CT-80Afrom 9:30 to 7:30 next day(once in 2h. During 07:30 to 21:30, patients were measured in sitting position, while during 23:30 to 05:30 in both sitting and supine position.RESULTS: A morning peak of IOP was shown at 7:30 in traditional position by using two measures with 22.05±3.608mmHg of NCT and 19.79±4.147mmHg of Accupen tonometer. The peak IOP in habitual position appeared in 5:30 with 21.64±4.814mmHg. The lowest IOP occurred in both position at 21:30 with 15.73±3.649mmHg. Both positions showed IOP trend of going up at night and then declining in the morning. CONCLUSION: The peak IOP in suspected glaucoma occurs mostly at early morning. Supine IOP of sleeping time is higher than that of sitting position.

Fixed-dose combination for adults accessing antiretroviral therapy

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SA HIV Clinicians Society

2013-02-01

Full Text Available This document serves to guide clinicians and programme managers on how to switch from 3 separate antiretroviral (ARV drugs to the new, single, fixed-dose combination (FDC tablet containing tenofovir (TDF, emtricitabine (FTC and efavirenz (EFV. Summary Transitioning from individual drugs to an FDC tablet needs to be managed carefully, particularly regarding stock management, ordering processes, supply-chain integrity and comprehensive patient counselling. Priority groups • Initially, FDC supply will be insufficient to provide for all FDC-suitable patients • Therefore, the National Department of Health (NDoH has recommended that the following patient groups be prioritized for FDC initiation/switch: • Priority group 1: All HIV-positive patients newly initiating ART – adults, adolescents and pregnant women (regardless of CD4 count (amendment to the guidelines for the prevention of mother-to-child transmission of HIV (PMTCT anticipated in April 2013 – and who do not have contra-indications to the FDC component drugs • Priority group 2: HIV-positive pregnant women and breastfeeding mothers currently stable on lamivudine (3TC, TDF and EFV • Priority group 3: Virologically suppressed patients on a stavudine (d4T-based regimen and who have normal renal function • Priority group 4: Stable patients receiving individual TDF, 3TC and EFV and who have tuberculosis (TB co-infection • Priority group 5: Stable patients receiving individual TDF, 3TC and EFV and who have other co-morbidites (e.g. hypertension, diabetes • Priority group 6: Patients receiving individual TDF, 3TC and EFV and who request to switch to the FDC treatment • Priority group 7: Patients receiving individual TDF, 3TC and EFV and who, after counselling, agree to switch to the FDC treatment. Important: Clinic staff must co-ordinate this process and only switch as many patients to the FDC tablet as stock allows. This should avoid patients being switched back and forth

Influence of drug load and physical form of cinnarizine in new SNEDDS dosing regimens

DEFF Research Database (Denmark)

Siqueira, Scheyla D V S; Müllertz, Anette; Gräeser, Kirsten

2017-01-01

The aim of this work was to evaluate the influence of drug load and physical form of cinnarizine (CIN) in self-nanoemulsifying drug delivery systems (SNEDDS) on absorption in rats. Further, the predictivity of the dynamic in vitro lipolysis model was evaluated. The following dosing regimens were......, compared to the aqueous suspension. Since the drug level in the aqueous phase is traditionally considered as the fraction available for absorption, a lack of in vitro-in vivo relation was observed. This study revealed that the physical form of CIN in the current SNEDDS does not affect CIN absorption...

Treatment of subclinical hypothyroidism in pregnancy using fixed thyroxine daily doses of 75 μg.

Science.gov (United States)

Penin, Manuel; Trigo, Cristina; López, Yolanda; Barragáns, María

2014-01-01

Treatment of hypothyroid pregnant women is usually calculated based on weight (1 μg/kg/day) and TSH levels. This study assessed the usefulness of treating these women with a fixed dose of 75 μg/day. All women with pregnancy diagnosed from January to August 2012 in the Vigo Health Area (Spain) without previous diagnosis of thyroid disease or thyroxine treatment and with TSH levels over 4,5 mUI/ml were enrolled by consecutive sampling. All 116 women in the sample were treated with a fixed daily dose of thyroxine 75 μg-thyroxine levels were measured at two, four, and six months, and thyroxine dose was modified if TSH level was lower than 0.3 or higher than 4.5 mUI/ml. A woman had a TSH level less than 0.3 mUI/ml in a test; reduction of thyroxine dose to 50 μg/day allowed for maintaining TSH level within the desired range until delivery. Six women had TSH levels over 4.5 mUI/ml in one test; in all of them, increase in thyroxine dose to 100 μg/day allowed for maintaining the level within the desired range until delivery. Fixed daily doses of thyroxine 75 μg allowed for achieving goal TSH levels in most of our pregnant women with subclinical hypothyroidism, irrespective of their weight and baseline TSH level. Copyright © 2013 SEEN. Published by Elsevier Espana. All rights reserved.

Clinical benefit of fixed-dose dual bronchodilation with glycopyrronium and indacaterol once daily in patients with chronic obstructive pulmonary disease

DEFF Research Database (Denmark)

Ulrik, Charlotte Suppli

2014-01-01

BACKGROUND AND AIM: Long-acting bronchodilators are the preferred option for maintenance therapy of patients with chronic obstructive pulmonary disease (COPD). The aim of this review is to provide an overview of the clinical studies evaluating the clinical efficacy of the once-daily fixed-dose du...... for chronic Obstructive Lung Disease [GOLD] spirometric criteria). Furthermore, a very recent study has shown that fixed-dose indacaterol/glycopyrronium improves exercise endurance time compared with placebo, although no significant difference was observed between fixed-dose indacaterol...

Nebivolol and valsartan as a fixed-dose combination for the treatment of hypertension.

Science.gov (United States)

Sander, Gary E; Giles, Thomas D

2015-04-01

The fixed-dose combination of nebivolol and valsartan drug has been clinically evaluated and demonstrated to represent a unique combination of nebivolol, a selective β1-adrenoceptor antagonist and a β3-adrenoceptor agonist; β3 receptor activation increases endothelial nitric oxide and produces vasodilation. Valsartan is highly selective angiotensin AT1 receptor blocker and exerts its major pharmacological effect by decreasing angiotensin II-induced vasoconstriction and production of aldosterone. The addition of nebivolol counteracts the effects of increased angiotensin II concentrations resulting from potent AT1 blockade. This review describes a recently completed trial establishing the efficacy of the nebivolol/valsartan combination. This review provides a literature search of pertinent pharmacological and clinical data that describes the mechanisms of both drugs individually and the results of a clinical trial comparing fixed-dose combinations of nebivolol with valsartan as compared with each drug as monotherapy. Fixed-dose combination drugs are intended to improve patient compliance and reduce drug costs, as well as to reduce long-term cardiovascular event rates and block counter-regulatory effects due to monotherapy. The vast majority of hypertensive patients will require at least two medications. We believe that the clinical evidence suggests that the combination of nebivolol with valsartan offers a definite clinical benefit, combining β1-adrenoceptor and angiotensin AT1 receptor blockade with β3 receptor activation and resultant increase in nitric oxide and vasodilation.

The colorimetric analysis of anti-tuberculosis fixed-dose combination tablets and capsules.

Science.gov (United States)

Ellard, G A

1999-11-01

The perceived need to demonstrate whether or not the actual amounts of rifampicin, isoniazid and pyrazinamide in fixed-dose combination tablets or capsules correspond to their stated drug contents. To adapt specific, robust and simple colorimetric methods that have been previously applied to measuring plasma and urinary rifampicin, isoniazid, pyrazinamide and ethambutol concentrations to estimate tablet and capsule drug contents. The methods were applied to the analysis of 14 commercially manufactured fixed-dose combinations: two capsule and three tablet formulations containing rifampicin and isoniazid; seven tablet formulations containing rifampicin, isoniazid and pyrazinamide; and two tablet formulations containing rifampicin, isoniazid, pyrazinamide and ethambutol. All the combined formulations contained near to their stated drug contents. Replicate analyses confirmed the excellent precision of the drug analyses. Such methods are not only rapid to perform but should be practical in many Third World situations with relatively modest laboratory facilities.

[Fixed-dose combination fluticasone propionate/formoterol for the treatment of asthma: a review of its pharmacology, efficacy and tolerability].

Science.gov (United States)

Quintano Jiménez, J A; Ginel Mendoza, L; Entrenas Costa, L M; Polo García, J

2016-02-01

The fixed-dose combination fluticasone propionate/formoterol (FPF) is a novel combination of a widely known and used inhaled glucocorticoid (IGC) and a long-acting β2-adrenergic agonist (LABA), available for the first time in a single device. This fixed-dose combination of FPF has a demonstrated efficacy and safety profile in clinical trials compared with its individual components and other fixed-dose combinations of IGC/LABA and is indicated for the treatment of persistent asthma in adults and adolescents. FPF is available in a wide range of doses that can adequately cover the therapeutic steps recommended by treatment guidelines, constituting a fixed-dose combination of GCI/LABA that is effective, rapid, well tolerated and with a reasonable acquisition cost. Various assessment agencies of the Spanish Autonomous Communities consider this combination to be an appropriate alternative therapy for asthma in the primary care setting. Copyright © 2016 Elsevier España, S.L.U. y Sociedad Española de Medicina Rural y Generalista (SEMERGEN). All rights reserved.

Thallium reinjection after stress-redistribution imaging. Does 24-hour delayed imaging after reinjection enhance detection of viable myocardium

International Nuclear Information System (INIS)

Dilsizian, V.; Smeltzer, W.R.; Freedman, N.M.; Dextras, R.; Bonow, R.O.

1991-01-01

Thallium reinjection immediately after conventional stress-redistribution imaging improves the detection of viable myocardium, as many myocardial regions with apparently 'irreversible' thallium defects on standard 3-4-hour redistribution images manifest enhanced thallium uptake after reinjection. Because the 10-minute period between reinjection and imaging may be too short, the present study was designed to determine whether 24-hour imaging after thallium reinjection provides additional information regarding myocardial viability beyond that obtained by imaging shortly after reinjection. We studied 50 patients with chronic stable coronary artery disease undergoing exercise thallium tomography, radionuclide angiography, and coronary arteriography. Immediately after the 3-4-hour redistribution images were obtained, 1 mCi thallium was injected at rest, and images were reacquired at 10 minutes and 24 hours after reinjection. The stress, redistribution, reinjection, and 24-hour images were then analyzed qualitatively and quantitatively. Of the 127 abnormal myocardial regions on the stress images, 55 had persistent defects on redistribution images by qualitative analysis, of which 25 (45%) demonstrated improved thallium uptake after reinjection. At the 24-hour study, 23 of the 25 regions (92%) with previously improved thallium uptake by reinjection showed no further improvement. Similarly, of the 30 regions determined to have irreversible defects after reinjection, 29 (97%) remained irreversible on 24-hour images. These findings were confirmed by the quantitative analysis. The mean normalized thallium activity in regions with enhanced thallium activity after reinjection increased from 57 +/- 13% on redistribution studies to 70 +/- 14% after reinjection but did not change at 24 hours (71 +/- 14%)

Effects of renal sympathetic denervation on 24-hour blood pressure variability

Directory of Open Access Journals (Sweden)

Christine Stefanie Zuern

2012-05-01

Full Text Available Background: In patients with arterial hypertension, increased blood pressure (BP variability contributes to end organ damage independently from mean levels of arterial BP. Increased BP variability has been linked to alterations in autonomic function including sympathetic overdrive. We hypothesized that catheter-based renal sympathetic denervation (RDN confers beneficial effects on BPV. Methods and Results: Eleven consecutive patients with therapy-refractory arterial hypertension (age 68.9±7.0 years; baseline systolic BP 189±23mmHg despite medication with 5.6±2.1 antihypertensive drugs underwent bilateral RDN. Twenty-four hour ambulatory blood pressure monitoring (ABPM was performed before RDN and six months thereafter. BPV was primarily assessed by means of standard deviation of 24-hour systolic arterial blood pressures (SDsys. Secondary measures of BPV were maximum systolic blood pressure (MAXsys and maximum difference between two consecutive readings of systolic BP (deltamaxsys over 24 hours. Six months after RDN, SDsys, MAXsys and deltamaxsys were significantly reduced from 16.9±4.6mmHg to 13.5±2.5mmHg (p=0.003, from 190±22mmHg to 172±20mmHg (p<0.001 and from 40±15mmHg to 28±7mmHg (p=0.006, respectively, without changes in concomitant antihypertensive therapy. Reductions of SDsys, MAXsys and deltamaxsys were observed in 10/11 (90.9%, 11/11 (100% and 9/11 (81.8% patients, respectively. Although we noted a significant reduction of systolic office blood pressure by 30.4±27.7mmHg (p=0.007, there was only a trend in reduction of average systolic BP assessed from ABPM (149±19mmHg to 142±18mmHg; p=0.086.Conclusions: In patients with therapy-refractory arterial hypertension, RDN leads to significant reductions of BP variability. Effects of RDN on BPV over 24 hours were more pronounced than on average levels of BP.

Radiation therapy and concurrent fixed dose amifostine with escalating doses of twice-weekly gemcitabine in advanced pancreatic cancer

International Nuclear Information System (INIS)

Yavuz, A. Aydin; Aydin, Fazil; Yavuz, Melek N.; Ilis, Esra; Ozdemir, Feyyaz

2001-01-01

Purpose: To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of twice-weekly gemcitabine (TW-G) when administered in conjunction with fixed dose amifostine (A) during external radiotherapy (RT) in patients with advanced pancreatic cancer. Methods and Materials: Ten patients with previously untreated, locally advanced, or asymptomatic-metastatic pancreatic adenocarcinoma were enrolled in this study. RT was delivered by using the standard four-field technique (1.8 Gy daily fractions, 45 Gy followed by a boost of 5.4 Gy, in 5-1/2 weeks). The starting dose of TW-G was 60 mg/m 2 (i.v., 30-min infusion), which is equal to the upper limit of previously reported MTD of TW-G when given without A during RT. A was given just before the TW-G, at a fixed dose of 340 mg/m 2 (i.v., rapid infusion). TW-G doses were escalated by 30-mg/m 2 increments in successive cohorts of 3 to 6 additional patients until DLT was observed. Toxicities were graded using the Radiation Therapy Oncology Group and National Cancer Institute Common Toxicity Criteria, version 2.0. Results: In general, therapy was well tolerated in patients treated at the first two dose levels of 60 mg/m 2 and 90 mg/m 2 . The DLT of TW-G given in conjunction with A during RT were neutropenia, thrombocytopenia, and nausea/vomiting at the dose level of 120 mg/m 2 . Of the 10 patients eligible for a median follow-up of 10 months, 5 remain alive; 1 complete responder, 3 partial responders, and 1 with stable disease. Conclusion: A dose of TW-G at a level of 90 mg/m 2 produced tolerable toxicity and it may possess significant activity when delivered in conjunction with 340 mg/m 2 dose of A during RT of the upper abdomen. Due to the higher MTD of TW-G seen in our study, we consider that the A supplementation may optimize the therapeutic index of TW-G-based chemoradiotherapy protocols in patients with pancreatic carcinoma

Pulse wave velocity 24-hour monitoring with one-site measurements by oscillometry

Directory of Open Access Journals (Sweden)

Posokhov IN

2013-02-01

Full Text Available Igor N PosokhovHemodynamic Laboratory Ltd, Nizhniy Novgorod, RussiaAbstract: This review describes issues for the estimation of pulse wave velocity (PWV under ambulatory conditions using oscillometric systems. The difference between the principles of measuring the PWV by the standard method and by oscillometry is shown, and information on device validation studies is summarized. It was concluded that currently oscillometry is a method that is very convenient to use in the 24-hour monitoring of the PWV, is relatively accurate, and is reasonably comfortable for the patient. Several indices with the same principles as those in the analysis of blood pressure in ambulatory monitoring of blood pressure, namely the assessment of load, variability, and circadian rhythm, are proposed.Keywords: pulse wave velocity, 24-hour monitoring, oscillometry

Physicians' attentional performance following a 24-hour observation period: do we need to regulate sleep prior to work?

Science.gov (United States)

Smyth, P; Maximova, K; Jirsch, J D

2017-08-01

The tradition of physicians working while sleep deprived is increasingly criticised. Medical regulatory bodies have restricted resident physician duty-hours, not addressing the greater population of physicians. We aimed to assess factors such as sleep duration prior to a 24-hour observation period on physicians' attention. We studied 70 physicians (mean age 38 years old (SD 10.8 years)): 36 residents and 34 faculty from call rosters at the University of Alberta. Among 70 physicians, 52 (74%) performed overnight call; 18 did not perform overnight call and were recruited to control for the learning effect of repetitive neuropsychological testing. Attentional Network Test (ANT) measured physicians' attention at the beginning and end of the 24-hour observation period. Participants self-reported ideal sleep needs, sleep duration in the 24 hours prior to (ie, baseline) and during the 24-hour observation period (ie, follow-up). Median regression models examined effects on ANT parameters. Sleep deprivation at follow-up was associated with reduced attentional accuracy following the 24-hour observation period, but only for physicians more sleep deprived at baseline. Other components of attention were not associated with sleep deprivation after adjusting for repetitive testing. Age, years since medical school and caffeine use did not impact changes in ANT parameters. Our study suggests that baseline sleep before 24 hours of observation impacts the accuracy of physicians' attentional testing at 24 hours. Further study is required to determine if optimising physician sleep prior to overnight call shifts is a sustainable strategy to mitigate the effects of sleep deprivation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

AUC versus peak-trough dosing of vancomycin: applying new pharmacokinetic paradigms to an old drug.

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Brown, Daniel L; Lalla, Christina D; Masselink, Andrew J

2013-08-01

To compare and contrast the pharmacokinetic/pharmacodynamic foundations of traditional "peak-trough" vancomycin dosing methods versus newer "area under the curve" (AUC) strategies. To propose a new AUC-based dosing chart for empirically determining an initial vancomycin dosing regimen designed to achieve a desired AUC24 using the minimum inhibitory concentration (MIC), creatinine clearance (CrCl), and vancomycin clearance (ClVanco). Peak-trough vancomycin dosing is designed to achieve a Cpeak of 20-40 mg/L and a Ctrough of 10-15 or 15-20 mg/L, depending on the severity of the infection and the nature of the pathogen. New treatment guidelines for vancomycin suggest that therapy should achieve an AUC24/MIC of ≥400. AUC-based vancomycin dosing derives the daily dose from ClVanco, MIC, and the desired AUC24/MIC, without consideration of the patient's weight. A vancomycin dosing chart is proposed that estimates ClVanco using the following formula developed by Matzke et al: ClVanco in L/h = [(CrClmL/min × 0.689) + 3.66] × 0.06, which simplifies to (CrClmL/min × 0.41) + 0.22. Two levels of dosing are included-high dose (Ctrough: 15-20 mg/L) and moderate dose (Ctrough: 10-15 mg/L). Although the chart has not been validated clinically, it represents the product of standard dosing equations that are used to determine a starting dosing regimen based on well-established vancomycin pharmacokinetic parameters. An understanding of pharmacokinetic and pharmacodynamic principles, including the relevance of AUC in relation to MIC, enables clinicians to make the best use of vancomycin dosing options. The proposed dosing chart is pharmacokinetically valid but has yet to be applied clinically. It provides a foundation for further study of how clinicians can determine an optimal AUC-based starting vancomycin dosing regimen without having to derive ClVanco or AUC24.

Comparison of different glucocorticoid regimens in the management of classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

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Ajish, T P; Praveen, V P; Nisha, B; Kumar, Harish

2014-11-01

There are recommendations regarding the total dose of hydrocortisone to be administered in the treatment of classical congenital adrenal hyperplasia (CAH) to achieve the twin objectives of glucocorticoid replacement and control of hyperandrogenism. However, there is evidence gap regarding the breakup, timing and type of the steroid regimen. Efficacy of three different glucocorticoid regimens having the same total dose of steroid, differing in either the timing or type of evening steroid administered, in achieving biochemical control of the disease was assessed. The study was done in 13 prepubertal children with classical CAH over a 6-month period with 2 months devoted to each regimen. We used a prospective cross-over design using 10-15 mg/m(2) total dose of hydrocortisone. Two-fifths of the total dose of hydrocortisone was administered in the morning and one-fifth of the total dose was administered at noon in all the regimens. The regimens differed in the timing of the evening dose of hydrocortisone, 06.00-07.00 pm in regimen 1 and 09.00-10.00 pm in regimen 2. The third regimen had the evening dose of hydrocortisone replaced by an equivalent dose of prednisolone suspension which was administered at 10.00 pm. Serum 17-hydroxyprogesterone and testosterone levels were compared to assess the efficacy of treatment regimens. The three different regimens were found to be similar in their ability to control 17-hydroxyprogesterone and testosterone levels. The percentage of patients with predefined criteria for biochemically controlled disease was similar in all the three regimens. However, there was a trend toward better control of 17-hydroxyprogesterone levels in patients receiving evening dose of prednisolone. There is no significant advantage in administering the hydrocortisone dose late at night in patients with classical CAH.

Severe Dopaminergic Neurotoxicity in Primates After a Common Recreational Dose Regimen of MDMA (``Ecstasy'')

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Ricaurte, George A.; Yuan, Jie; Hatzidimitriou, George; Cord, Branden J.; McCann, Una D.

2002-09-01

The prevailing view is that the popular recreational drug (+/-)3,4-methylenedioxymethamphetamine (MDMA, or ``ecstasy'') is a selective serotonin neurotoxin in animals and possibly in humans. Nonhuman primates exposed to several sequential doses of MDMA, a regimen modeled after one used by humans, developed severe brain dopaminergic neurotoxicity, in addition to less pronounced serotonergic neurotoxicity. MDMA neurotoxicity was associated with increased vulnerability to motor dysfunction secondary to dopamine depletion. These results have implications for mechanisms of MDMA neurotoxicity and suggest that recreational MDMA users may unwittingly be putting themselves at risk, either as young adults or later in life, for developing neuropsychiatric disorders related to brain dopamine and/or serotonin deficiency.

Executive Functions are not Affected by 24 Hours of Sleep Deprivation: A Color-Word Stroop Task Study.

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Dixit, Abhinav; Mittal, Tushar

2015-01-01

Sleep is an important factor affecting cognitive performance. Sleep deprivation results in fatigue, lack of concentration, confusion and sleepiness along with anxiety, depression and irritability. Sleep deprivation can have serious consequences in professions like armed forces and medicine where quick decisions and actions need to be taken. Color-Word Stroop task is one of the reliable tests to assess attention and it analyzes the processing of information in two dimensions i.e., reading of words and naming of colour. The evidence regarding the effect of sleep deprivation on Stroop interference is conflicting. The present study evaluated the effect of 24 hours of sleep deprivation on reaction time and interference in Stroop task. The present study was done on 30 healthy male medical student volunteers in the age group of 18-25 years after taking their consent and clearance from Institute Ethics Committee. Recordings of Stroop task were at three times: baseline (between 7-9 am), after 12 hours (7-9 pm) and after 24 hours (7-9 am, next day). The subjects were allowed to perform normal daily activities. The study revealed a significant increase in reaction time after 24 hours of sleep deprivation in comparison to baseline and after 12 hours of sleep deprivation. There was no significant change in interference and facilitation after sleep deprivation in comparison to baseline. The number of errors also did not show any significant change after sleep deprivation. The study indicated that there was slowing of responses without change in executive functions after 24 hours of sleep deprivation. It is probable that 24 hours of sleep deprivation does not bring about change in areas of brain affecting executive functions in healthy individuals who have normal sleep cycle. The present study indicated that in professions like armed forces and medicine working 24 hours at a stretch can lead to decrease in motor responses without affecting information processing and judgment

Delay of constant light-induced persistent vaginal estrus by 24-hour time cues in rats.

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Weber, A L; Adler, N T

1979-04-20

The normal ovarian cycle of female rats is typically replaced by persistent estrus when these animals are housed under constant light. Evidence presented here shows that the maintenance of periodicity in the environment can at least delay (if not prevent) the photic induction of persistent vaginal estrus. Female rats in constant light were exposed to vaginal smearing at random times or at the same time every day. In another experiment, female rats were exposed to either constant bright light, constant dim light, or a 24-hour photic cycle of bright and dim light. The onset of persistent vaginal estrus was delayed in rats exposed to 24-hour time cues even though the light intensities were the same as or greater than those for the aperiodic control groups. The results suggest that the absence of 24-hour time cues in constant light contributes to the induction of persistent estrus.

Provider knowledge of treatment policy and dosing regimen with artemether-lumefantrine and quinine in malaria-endemic areas of western Kenya

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Watsierah Carren A

2012-12-01

Full Text Available Abstract Background Due to widespread anti-malarial drug resistance in many countries, Kenya included, artemisinin-based Combination Therapy (ACT has been adopted as the most effective treatment option against malaria. Artemether-lumefantrine (AL is the first-line ACT for treatment of uncomplicated malaria in Kenya, while quinine is preferred for complicated and severe malaria. Information on the providers’ knowledge and practices prior to or during AL and quinine implementation is scanty. The current study evaluated providers’ knowledge and practices of treatment policy and dosing regimens with AL and quinine in the public, private and not-for-profit drug outlets. Methods A cross-sectional survey using three-stage sampling of 288 (126 public, 96 private and 66 not-for-profits providers in drug outlets was conducted in western Kenya in two Plasmodium falciparum-endemic regions with varying malarial risk. Information on provider in-service training, knowledge (qualification, treatment policy, dosing regimen, recently banned anti-malarials and on practices (request for written prescription, prescription of AL, selling partial packs and advice given to patients after prescription, was collected. Results Only 15.6% of providers in private outlets had received any in-service training on AL use. All (100% in public and majority (98.4% in not-for-profit outlets mentioned AL as first line-treatment drug. Quinine was mentioned as second-line drug by 47.9% in private outlets. A total of 92.0% in public, 57.3% in private and 78.8% in not-for-profit outlets stated correct AL dose for adults. A total of 85.7% of providers in public, 30.2% in private and 41.0% in not-for-profit outlets were aware that SP recommendations changed from treatment for mild malaria to IPTp in high risk areas. In-service training influenced treatment regimen for uncomplicated malaria (P = 0.039 and P = 0.039 and severe malaria (P P = 0.002 in children and adults

Targeted Temperature Management for 48 vs 24 Hours and Neurologic Outcome After Out-of-Hospital Cardiac Arrest

DEFF Research Database (Denmark)

Kirkegaard, Hans; Søreide, Eldar; de Haas, Inge

2017-01-01

Importance: International resuscitation guidelines recommend targeted temperature management (TTM) at 33°C to 36°C in unconscious patients with out-of-hospital cardiac arrest for at least 24 hours, but the optimal duration of TTM is uncertain. Objective: To determine whether TTM at 33°C for 48....... Secondary outcomes included 6-month mortality, including time to death, the occurrence of adverse events, and intensive care unit resource use. Results: In 355 patients who were randomized (mean age, 60 years; 295 [83%] men), 351 (99%) completed the trial. Of these patients, 69% (120/175) in the 48-hour.......5%; 95% CI, -16.1% to 3.1%; RR, 0.81; 95% CI, 0.59-1.11; P = .19). There was no significant difference in the time to mortality between the 48-hour group and the 24-hour group (hazard ratio, 0.79; 95% CI, 0.54-1.15; P = .22). Adverse events were more common in the 48-hour group (97%) than in the 24-hour...

Safety and adherence to intermittent pre-exposure prophylaxis (PrEP) for HIV-1 in African men who have sex with men and female sex workers.

Science.gov (United States)

Mutua, Gaudensia; Sanders, Eduard; Mugo, Peter; Anzala, Omu; Haberer, Jessica E; Bangsberg, David; Barin, Burc; Rooney, James F; Mark, David; Chetty, Paramesh; Fast, Patricia; Priddy, Frances H

2012-01-01

Little is known about safety of and adherence to intermittent HIV PrEP regimens, which may be more feasible than daily dosing in some settings. We present safety and adherence data from the first trial of an intermittent PrEP regimen among Kenyan men who have sex with men (MSM) and female sex workers (FSW). MSM and FSW were randomized to daily oral FTC/TDF or placebo, or intermittent (Monday, Friday and within 2 hours after sex, not to exceed one dose per day) oral FTC/TDF or placebo in a 2:1:2:1 ratio; volunteers were followed monthly for 4 months. Adherence was assessed with the medication event monitoring system (MEMS). Sexual activity data were collected via daily text message (SMS) queries and timeline followback interviews with a one-month recall period. Sixty-seven men and 5 women were randomized into the study. Safety was similar among all groups. Median MEMS adherence rates were 83% [IQR: 63-92] for daily dosing and 55% [IQR:28-78] for fixed intermittent dosing (p = 0.003), while adherence to any post-coital doses was 26% [IQR:14-50]. SMS response rates were low, which may have impaired measurement of post-coital dosing adherence. Acceptability of PrEP was high, regardless of dosing regimen. Adherence to intermittent dosing regimens, fixed doses, and in particular coitally-dependent doses, may be more difficult than adherence to daily dosing. However, intermittent dosing may still be appropriate for PrEP if intracellular drug levels, which correlate with prevention of HIV acquisition, can be attained with less than daily dosing and if barriers to adherence can be addressed. Additional drug level data, qualitative data on adherence barriers, and better methods to measure sexual activity are necessary to determine whether adherence to post-coital PrEP could be comparable to more standard regimens. ClinicalTrials.gov NCT00971230.

Reproducibility of two, three, four and five 24-hour recalls in peri ...

African Journals Online (AJOL)

2011-06-10

Jun 10, 2011 ... participants' ability to accurately record or recall food consumption, describe food .... used.16 The accuracy of food item and portion size data captured for ..... Four 24-hour recalls are more practical and cost-effective, and carry.

Impedance and electrically evoked compound action potential (ECAP drop within 24 hours after cochlear implantation.

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Joshua Kuang-Chao Chen

Full Text Available Previous animal study revealed that post-implantation electrical detection levels significantly declined within days. The impact of cochlear implant (CI insertion on human auditory pathway in terms of impedance and electrically evoked compound action potential (ECAP variation within hours after surgery remains unclear, since at this time frequency mapping can only commence weeks after implantation due to factors associated with wound conditions. The study presented our experiences with regards to initial switch-on within 24 hours, and thus the findings about the milieus inside cochlea within the first few hours after cochlear implantation in terms of impedance/ECAP fluctuations. The charts of fifty-four subjects with profound hearing impairment were studied. A minimal invasive approach was used for cochlear implantation, characterized by a small skin incision (≈ 2.5 cm and soft techniques for cochleostomy. Impedance/ECAP was measured intro-operatively and within 24 hours post-operatively. Initial mapping within 24 hours post-operatively was performed in all patients without major complications. Impedance/ECAP became significantly lower measured within 24 hours post-operatively as compared with intra-operatively (p<0.001. There were no differences between pre-operative and post-operative threshold for air-conduction hearing. A significant drop of impedance/ECAP in one day after cochlear implantation was revealed for the first time in human beings. Mechanisms could be related to the restoration of neuronal sensitivity to the electrical stimulation, and/or the interaction between the matrix enveloping the electrodes and the electrical stimulation of the initial switch-on. Less wound pain/swelling and soft techniques both contributed to the success of immediate initial mapping, which implied a stable micro-environment inside the cochlea despite electrodes insertion. Our research invites further studies to correlate initial impedance/ECAP changes

[Pharmacokinetic monitoring of 24-hour infusion of methotrexate in an adult population with non-Hodgkin lymphoma].

Science.gov (United States)

Fernández Megía, M J; Alós Almiñana, M; Esquer Borrás, J

2004-01-01

To describe the behavior and variability of methotrexate (MTX) pharmacokinetic parameters in patients with non-Hodgkin lymphoma (NHL) and to suggest a monitoring system to optimize sample collection using a bayesian method. Two adult patient groups diagnosed with different NHL types were studied. Group I was made up of 9 patients aged 53 +/- 16 years who received MTX at a mean dose of 1.652 +/- 327 mg per course. Group II was made up of 7 patients aged 53 +/- 14 years who received MTX at a mean dose of 1.862 +/- 220 mg per course. No statistically significant differences between groups were seen. Serum MTX measurements were performed using polarized immunofluorescence (TDx system). The pharmacokinetic analysis was performed using Abbottbase Pharmacokinetics Systems (PKS) software, adjusting experimental data according to a bicompartmental linear model for intravenous delivery using non-linear regression in Group I and Bayesian estimates in Group II. By estimating mean square error and linear regression between predicted and experimental concentrations, the capability of the Bayesian method implemented in PKS to predict plasma MTX concentration at 48 hours post-infusion was evaluated. The safety of MTX therapy was assessed using patient medical histories and then scoring toxicity using the WHO scale. Pharmacokinetic parameters obtained for group I included: alpha (h(-1)) = 0.38 +/- 0.12; beta (h(-1)) = 0.07 +/- 0.03; K12 (h(-1)) = 0.02 +/- 0.02; K21 (h(-1)) = 0.09 +/- 0.09; K13 (h(-1)) = 0.34 +/- 0.12; Vc (l/kg) = 0.53 +/- 0.23; Vss (l/kg) = 0.62 +/- 0.26; Cl (l/kg.h) = 0.16 +/- 0.06. The error for the PKS population model in measuring plasma MTX concentration at 48 hours post-infusion in Group II was calculated in accordance with three sampling schemes -12 h, 24 h, and both. It was -14.58 x 10(-3), -15.70 x 10(-3) and -14.67 x 10(-3), respectively. Eqm was 9.58 x 10(-3), 2.39 x 10(-3), and 1.02 x 10(-3), respectively. An MTX monitoring scheme is suggested based on

Etanercept provides an effective, safe and flexible short- and long-term treatment regimen for moderate-to-severe psoriasis: a systematic review of current evidence.

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Strohal, Robert; Chimenti, Sergio; Vena, Gino Antonio; Girolomoni, Giampiero

2013-06-01

The treatment of psoriasis requires long-lasting intervention. Conventional treatments for psoriasis comprise topical, phototherapeutic and systemic modalities, such as methotrexate or cyclosporine. Biological therapies are advocated by treatment guidelines for the use in moderate-to-severe psoriasis, when conventional treatments have failed, are contraindicated or are associated with severe adverse events. Etanercept is an anti-TNF recombinant fusion protein that has emerged as a standard biologic treatment option for moderate-to-severe psoriasis. The present review summarizes data from pivotal and post-marketing randomized controlled etanercept trials to treat moderate-to-severe psoriasis for 24 weeks and longer. During the first 12 weeks, etanercept can be administered in different dosing regimens: 50 mg twice weekly (BIW) and 50 mg once weekly. Although both regimens are effective, it has been shown that the 50 mg BIW dosage leads to higher response rates at week 24. In addition, after 24 weeks' treatment etanercept provides the unique possibility of continuous or intermittent long-term treatment programmes. The medium- to long-term efficacy of etanercept was consistent, regardless of whether etanercept therapy was interrupted or continuous. Taking the chronic nature of psoriasis into account, this flexibility in dosing regimen bestows a key advantage in facilitating individualisation of long-term treatment according to patient needs.

Comparison of 24-hour urinary protein and protein-to-creatinine ratio in the assessment of proteinuria

International Nuclear Information System (INIS)

Wahbeh, Ayman M; Ewais, Mohammad H; Elsharif, Mahamed E

2009-01-01

To determine the correlation between protein-to-creatinine ratio (PCR) and 24-hour urinary protein (UP), we measured proteinuria in 68 patients attending the nephrology clinic at Jordan University Hospital by 24-hour urine protein excretion and protein-to-creatinine ratio. The cutoff values for spot urine protein-to-creatinine ratio in predicting 24-hour protein 'threshold' excretion of 0.5, 1.0 and 3.5 g/day were determined using receiver operating characteristic curves. A very good correlation (r= 0.832, P< 0.0001) was found between spot urine protein-to-creatinine ratio and 24-hour urine protein excretion. Bland-Altman plot showed the two tests had reasonable limits of agreement at low level of protein excretion but the limits became wider as the protein excretion increased. For protein excretion < 2.0 g/day, the limits of agreement of spot urine (PCR) and (UP) were +1.48 and -1.2 g/day. The spot urine protein-to-creatinine ratios of 0.72 (sensitivity 0.97; specificity 1.0), 1.2 (0.97; 0.89) and 3.23 (1.0; 0.86) mg/mg reliably predicted 24-hour urine total protein equivalent 'thresholds' of 0.5, 1.0 and 3.5 g/day, respectively. We conclude that the protein-to-creatinine ratio in spot urine specimens is an accurate, convenient, and reliable method to estimate the protein excretion in urine. However, the protein-to-creatinine ratio will likely be within clinically acceptable limits only when proteinuria is at reasonably low levels. (author)

Interferência do intervalo de administração da droga sobre a nefrotoxicidade da gentamicina em ratos Influence of the dose regimen on the gentamicin nephrotoxicity in rats

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Verônica Cunha Rodrigues Oliveira

2001-06-01

Full Text Available A insuficiência renal aguda (IRA que apresenta índice de mortalidade em torno de 50%, pode ser definida como um abrupto declínio da filtração glomerular, resultante de isquemia ou toxicidade. A nefrotoxicidade por drogas é uma das etiologias mais freqüentes (27% e sugere-se que o intervalo de administração da droga pode interferir neste efeito colateral, entretanto o melhor regime de administração ainda não está bem estabelecido. Este conhecimento proporcionaria uma atuação mais direcionada de enfermagem na prevenção desta IRA hospitalar. Os resultados obtidos nesta pesquisa, indicam que a infusão única de gentamicina determina menor nefrotoxicidade, provavelmente devido à redução da sua concentração plasmática nas 24hs, diminuindo o acúmulo intracelular deste fármaco, um dos principais mecanismos celulares deste tipo de lesão. Este regime de tratamento mostra portanto vantagens quanto ao custo, efeito nefrotóxico e segurança quanto à eficácia terapêutica.The acute renal failure (ARF, that still presents a righ mortality rate (50% can be defined as an abrupt decline of the glomerular filtration, resultant of isquemic or toxicity event. The drugs nephrotoxicity is one of the most frequent cause (27% of ARF and it is suggested that the interval of administration of the drug can interfere in this side effect, however the best administration regimen is not very well established. This study evaluated the renal function of rats that received gentamicin (100mg/kg in one dose or in two doses (2x 50mg/kg,by intraperitoneal infusion. The results obtained in this research, indicated that the single infusion of gentamicin determined smaller nephrotoxicity by the reduction of serum concentration of this drug in 24 hours, decreasing the intracelular accumulation of this gentamicin, which is one of the main cellular mechanisms of this renal injury. The single dose treatment regime, otherwise, showes advantages not only related

Comparison of two dose regimens of ibuprofen for the closure of patent ductus arteriosus in preterm newborns,

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Laura Vargas Dornelles

2016-06-01

Full Text Available Abstract Objective: To compare the efficacy of intravenous ibuprofen at high (20-10-10 mg/kg/dose and low doses (10-5-5 mg/kg/dose the closure of patent ductus arteriosus in preterm newborns. Methods: A cohort study with historical control of newborns that received high- and low-dose intravenous ibuprofen, from 2010 to 2013 in a neonatal intensive care unit, for closure of the patent ductus arteriosus, documented by echocardiography. Secondary outcomes included the number of ibuprofen cycles, incidence of bronchopulmonary dysplasia, necrotizing enterocolitis, changes in renal function, and death. Results: Seventy-seven patients received three doses of ibuprofen for the treatment of patent ductus arteriosus, with 33 receiving high-dose and 44 low-dose therapy. The ductus closed after the first cycle in 25 (56.8% low-dose patients and in 17 (51.5% high-dose patients (p > 0.99. Sixteen patients received a second cycle of ibuprofen, and the ductus closed in 50% after low-dose and in 60% after high-dose therapy (p > 0.99. Seven patients required surgery for ductus closure, 13.6% in the low-dose group and 3% in the high-dose group (p = 0.22. Thirty-nine patients developed bronchopulmonary dysplasia, 50% in the low-dose group and 51.5% in the high-dose group (p > 0.99. Twenty-two (50% low-dose patients died vs. 15 (45.5% high-dose patients (p = 0.86. Conclusions: There was no difference in closure of the ductus arteriosus or occurrence of adverse effects between the two dose regimens.

ASSOCIATION OF DAIRY CONSUMPTION AND 24-HOUR BLOOD PRESSURE IN OLDER ADULTS WITH HYPERTENSION.

Science.gov (United States)

Lana, Alberto; Banegas, Jose R; Guallar-Castillón, Pilar; Rodríguez-Artalejo, Fernando; Lopez-Garcia, Esther

2018-05-25

The aim was to examine the association between habitual consumption of dairy products and 24-h ambulatory blood pressure monitoring among older adults with hypertension. We conducted an analysis of 715 community-living hypertensive adults aged ≥60. Habitual dairy consumption was assessed with a validated diet history. Blood pressure was recorded by 24-hour ambulatory blood pressure monitoring; controlled blood pressure was defined as 24-hour blood pressure blood pressure 1.40 mm Hg higher (95% confidence interval: 0.01, 2.81) than consumers of blood pressure 1.74 mm Hg lower (95% confidence interval: -3.26, -0.23) than consumers of blood pressure was 1.83 (1.05-3.08) for those consuming ≥7 servings/wk of low-fat milk/yogurt, when comparing with consumers of blood pressure. Regular consumption of low-fat milk/yogurt was associated with lower 24-h diastolic blood pressure and with better blood pressure control among older adults with hypertension. Copyright © 2018. Published by Elsevier Inc.

Tramadol/paracetamol fixed-dose combination in the treatment of moderate to severe pain

Science.gov (United States)

Pergolizzi, Joseph V; van de Laar, Mart; Langford, Richard; Mellinghoff, Hans-Ulrich; Merchante, Ignacio Morón; Nalamachu, Srinivas; O’Brien, Joanne; Perrot, Serge; Raffa, Robert B

2012-01-01

Pain is the most common reason patients seek medical attention and pain relief has been put forward as an ethical obligation of clinicians and a fundamental human right. However, pain management is challenging because the pathophysiology of pain is complex and not completely understood. Widely used analgesics such as nonsteroidal anti-inflammatory drugs (NSAIDs) and paracetamol (acetaminophen) have been associated with adverse events. Adverse event rates are of concern, especially in long-term treatment or at high doses. Paracetamol and NSAIDs are available by prescription, over the counter, and in combination preparations. Patients may be unaware of the risk associated with high dosages or long-term use of paracetamol and NSAIDs. Clinicians should encourage patients to disclose all medications they take in a “do ask, do tell” approach that includes patient education about the risks and benefits of common pain relievers. The ideal pain reliever would have few risks and enhanced analgesic efficacy. Fixed-dose combination analgesics with two or more agents may offer additive or synergistic benefits to treat the multiple mechanisms of pain. Therefore, pain may be effectively treated while toxicity is reduced due to lower doses. One recent fixed-dose combination analgesic product combines tramadol, a centrally acting weak opioid analgesic, with low-dose paracetamol. Evidence-based guidelines recognize the potential value of combination analgesics in specific situations. The current guideline-based paradigm for pain treatment recommends NSAIDs for ongoing use with analgesics such as opioids to manage flares. However, the treatment model should evolve how to use low-dose combination products to manage pain with occasional use of NSAIDs for flares to avoid long-term and high-dose treatment with these analgesics. A next step in pain management guidelines should be targeted therapy when possible, or low-dose combination therapy or both, to achieve maximal efficacy with

Efficacy and acceptability of a mifepristone-misoprostol combined regimen for early induced abortion among women in Mexico City.

Science.gov (United States)

Peña, Melanie; Dzuba, Ilana G; Smith, Patricio Sanhueza; Mendoza, Luis Jorge Arellano; Bousiéguez, Manuel; Martínez, María Laura García; Polanco, Ranulfo Ríos; Villalón, Antonio Eduardo Flores; Winikoff, Beverly

2014-10-01

To evaluate the experience of women receiving mifepristone-misoprostol for early induced abortion in public sector facilities in the Federal District of Mexico City. An open-label prospective study was conducted with 1000 pregnant women who sought induced abortion with a pregnancy of up to 63days of gestation, as measured from the date of their last menstrual period. The study was conducted in three public sector healthcare facilities: two secondary level hospitals and one primary care clinic. Women ingested 200mg mifepristone on day 1, followed by 800μg buccal misoprostol 24hours later, and they returned for follow-up on day 8. The primary outcome was complete abortion without recourse to surgical intervention. A total of 971 women received mifepristone-misoprostol and were included in the analysis for efficacy of treatment. The overall efficacy of the combined medical abortion regimen studied was 97.3% (n=945); the success rate did not vary significantly by gestational age (95.9%-100%; P=0.449). Most women (n=922, 95.0%) had a successful induced abortion with only one dose of misoprostol. The combined mifepristone and buccal misoprostol regimen was found to be highly effective and acceptable among Mexican women. www.ClinicalTrials.gov: NCT00386282. Copyright © 2014 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Circadian polymorphisms in night owls, in bipolars, and in non-24-hour sleep cycles.

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Kripke, Daniel F; Klimecki, Walter T; Nievergelt, Caroline M; Rex, Katharine M; Murray, Sarah S; Shekhtman, Tatyana; Tranah, Gregory J; Loving, Richard T; Lee, Heon-Jeong; Rhee, Min Kyu; Shadan, Farhad F; Poceta, J Steven; Jamil, Shazia M; Kline, Lawrence E; Kelsoe, John R

2014-10-01

People called night owls habitually have late bedtimes and late times of arising, sometimes suffering a heritable circadian disturbance called delayed sleep phase syndrome (DSPS). Those with DSPS, those with more severe progressively-late non-24-hour sleep-wake cycles, and those with bipolar disorder may share genetic tendencies for slowed or delayed circadian cycles. We searched for polymorphisms associated with DSPS in a case-control study of DSPS research participants and a separate study of Sleep Center patients undergoing polysomnography. In 45 participants, we resequenced portions of 15 circadian genes to identify unknown polymorphisms that might be associated with DSPS, non-24-hour rhythms, or bipolar comorbidities. We then genotyped single nucleotide polymorphisms (SNPs) in both larger samples, using Illumina Golden Gate assays. Associations of SNPs with the DSPS phenotype and with the morningness-eveningness parametric phenotype were computed for both samples, then combined for meta-analyses. Delayed sleep and "eveningness" were inversely associated with loci in circadian genes NFIL3 (rs2482705) and RORC (rs3828057). A group of haplotypes overlapping BHLHE40 was associated with non-24-hour sleep-wake cycles, and less robustly, with delayed sleep and bipolar disorder (e.g., rs34883305, rs34870629, rs74439275, and rs3750275 were associated with n=37, p=4.58E-09, Bonferroni p=2.95E-06). Bright light and melatonin can palliate circadian disorders, and genetics may clarify the underlying circadian photoperiodic mechanisms. After further replication and identification of the causal polymorphisms, these findings may point to future treatments for DSPS, non-24-hour rhythms, and possibly bipolar disorder or depression.

Short-Term Dosage Regimen for Stimulation-Induced Long-Lasting Desynchronization

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Thanos Manos

2018-04-01

Full Text Available In this paper, we computationally generate hypotheses for dose-finding studies in the context of desynchronizing neuromodulation techniques. Abnormally strong neuronal synchronization is a hallmark of several brain disorders. Coordinated Reset (CR stimulation is a spatio-temporally patterned stimulation technique that specifically aims at disrupting abnormal neuronal synchrony. In networks with spike-timing-dependent plasticity CR stimulation may ultimately cause an anti-kindling, i.e., an unlearning of abnormal synaptic connectivity and neuronal synchrony. This long-lasting desynchronization was theoretically predicted and verified in several pre-clinical and clinical studies. We have shown that CR stimulation with rapidly varying sequences (RVS robustly induces an anti-kindling at low intensities e.g., if the CR stimulation frequency (i.e., stimulus pattern repetition rate is in the range of the frequency of the neuronal oscillation. In contrast, CR stimulation with slowly varying sequences (SVS turned out to induce an anti-kindling more strongly, but less robustly with respect to variations of the CR stimulation frequency. Motivated by clinical constraints and inspired by the spacing principle of learning theory, in this computational study we propose a short-term dosage regimen that enables a robust anti-kindling effect of both RVS and SVS CR stimulation, also for those parameter values where RVS and SVS CR stimulation previously turned out to be ineffective. Intriguingly, for the vast majority of parameter values tested, spaced multishot CR stimulation with demand-controlled variation of stimulation frequency and intensity caused a robust and pronounced anti-kindling. In contrast, spaced CR stimulation with fixed stimulation parameters as well as singleshot CR stimulation of equal integral duration failed to improve the stimulation outcome. In the model network under consideration, our short-term dosage regimen enables to robustly induce

Short-Term Dosage Regimen for Stimulation-Induced Long-Lasting Desynchronization.

Science.gov (United States)

Manos, Thanos; Zeitler, Magteld; Tass, Peter A

2018-01-01

In this paper, we computationally generate hypotheses for dose-finding studies in the context of desynchronizing neuromodulation techniques. Abnormally strong neuronal synchronization is a hallmark of several brain disorders. Coordinated Reset (CR) stimulation is a spatio-temporally patterned stimulation technique that specifically aims at disrupting abnormal neuronal synchrony. In networks with spike-timing-dependent plasticity CR stimulation may ultimately cause an anti-kindling, i.e., an unlearning of abnormal synaptic connectivity and neuronal synchrony. This long-lasting desynchronization was theoretically predicted and verified in several pre-clinical and clinical studies. We have shown that CR stimulation with rapidly varying sequences (RVS) robustly induces an anti-kindling at low intensities e.g., if the CR stimulation frequency (i.e., stimulus pattern repetition rate) is in the range of the frequency of the neuronal oscillation. In contrast, CR stimulation with slowly varying sequences (SVS) turned out to induce an anti-kindling more strongly, but less robustly with respect to variations of the CR stimulation frequency. Motivated by clinical constraints and inspired by the spacing principle of learning theory, in this computational study we propose a short-term dosage regimen that enables a robust anti-kindling effect of both RVS and SVS CR stimulation, also for those parameter values where RVS and SVS CR stimulation previously turned out to be ineffective. Intriguingly, for the vast majority of parameter values tested, spaced multishot CR stimulation with demand-controlled variation of stimulation frequency and intensity caused a robust and pronounced anti-kindling. In contrast, spaced CR stimulation with fixed stimulation parameters as well as singleshot CR stimulation of equal integral duration failed to improve the stimulation outcome. In the model network under consideration, our short-term dosage regimen enables to robustly induce long

Efficacy of three-week oxytetracycline or rifampin monotherapy compared with a combination regimen against the filarial nematode Onchocerca ochengi.

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Bah, Germanus S; Ward, Emma L; Srivastava, Abhishek; Trees, Alexander J; Tanya, Vincent N; Makepeace, Benjamin L

2014-01-01

Onchocerciasis (river blindness), caused by the filarial nematode Onchocerca volvulus, is a major cause of visual impairment and dermatitis in sub-Saharan Africa. As O. volvulus contains an obligatory bacterial symbiont (Wolbachia), it is susceptible to antibiotic chemotherapy, although current regimens are considered too prolonged for community-level control programs. The aim of this study was to compare the efficacies of oxytetracycline and rifampin, administered separately or in combination, against a close relative of O. volvulus (Onchocerca ochengi) in cattle. Six animals per group were treated with continuous or intermittent oxytetracycline regimens, and effects on adult worm viability, dermal microfilarial loads, and Wolbachia density in worm tissues were assessed. Subsequently, the efficacies of 3-week regimens of oxytetracycline and rifampin alone and a combination regimen were compared, and rifampin levels in plasma and skin were quantified. A 6-month regimen of oxytetracycline with monthly dosing was strongly adulticidal, while 3-week and 6-week regimens exhibited weaker adulticidal effects. However, all three regimens achieved >2-log reductions in microfilarial load. In contrast, rifampin monotherapy and oxytetracycline-rifampin duotherapy failed to induce substantive reductions in either adult worm burden or microfilarial load, although a borderline effect on Wolbachia density was observed following duotherapy. Dermal rifampin levels were maintained above the MIC for >24 h after a single intravenous dose. We conclude that oxytetracycline-rifampin duotherapy is less efficacious against O. ochengi than oxytetracycline alone. Further studies will be required to determine whether rifampin reduces oxytetracycline bioavailability in this system, as suggested by human studies using other tetracycline-rifampin combinations.

Respiratory Rate During the First 24 Hours of Life in Healthy Term Infants.

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Tveiten, Lars; Diep, Lien My; Halvorsen, Thomas; Markestad, Trond

2016-04-01

Abnormal respiratory rate (RR) is a key symptom of disease in the newborn. The aim of this study was to establish the reference range for RR during the first 24 hours of life in healthy infants born at term. Infants were included at the hospital postnatal ward when time permitted. During sleep or a defined quiet state, RR was counted at 2, 4, 8, 16, and 24 hours by placing the bell of a stethoscope in front of the nostrils and mouth for 60 seconds. Data on maternal health, pregnancies, and births were obtained from medical records and the Medical Birth Registry of Norway. The study included 953 infants. Median RRs were 46 breaths/minute at 2 hours, thereafter 42 to 44 breaths/minute. The 95th percentile was 65 breaths/minute at 2 hours, thereafter 58 to 60 breaths/minute. The fifth percentile was 30 to 32 breaths/minute. Within these limits, the intraindividual variation was wide. The overall mean RR was 5.2 (95% confidence interval [CI], 4.7 to 5.7, P < .001) breaths/minute higher while awake than during sleep, 3.1 (95% CI, 1.5 to 4.8, P < .001) breaths/minute higher after heavy meconium staining of the amniotic fluid, and 1.6 (95% CI, 0.8 to 2.4, P < .001) breaths/minute higher in boys than girls. RR did not differ for infants born after vaginal versus cesarean deliveries. The RR percentiles established from this study allow for a scientifically based use of RR when assessing newborn infants born at term. Copyright © 2016 by the American Academy of Pediatrics.

Profile of a fixed-dose combination of tiotropium/olodaterol and its potential in the treatment of COPD

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Muruganandan S

2015-06-01

Full Text Available Sanjeevan Muruganandan,1 Lata Jayaram2,3 1Department of Respiratory and Sleep Medicine, Austin Health, 2Department of Respiratory and Sleep Medicine, Western Health, 3University of Melbourne, Melbourne, Victoria, Australia Abstract: Chronic obstructive pulmonary disease (COPD is a progressive, debilitating disorder that results in frequent exacerbations and impacts quality of life. It represents a growing burden of health care cost, both from societal and economic perspectives. Short- and long-acting bronchodilators remain the mainstay of therapy in COPD patients. New fixed-dose combination inhalers with novel pharmacological combinations of long-acting β2-agonists and muscarinic antagonists and delivered once-daily through a variety of devices are currently being developed and licensed for the treatment of COPD. There is mounting research suggesting that combining a fixed dose of a β2-agonist and a muscarinic antagonist achieves better bronchodilation and clinical outcomes compared with either agent alone. These once-daily dosing inhalers are anticipated to impact favorably on patient preference and compliance. This review examines the fixed-dose combination of tiotropium bromide and olodaterol delivered by a Respimat® Soft Mist™ inhaler at doses of 2.5/5 µg and 5/5 µg in moderate-to-very-severe COPD, and its potential role in COPD compared with other long-acting β2-agonist with long-acting muscarinic antagonist combinations and delivery devices. Keywords: fixed-dose combination inhalers, olodaterol, tiotropium bromide, COPD treatment, long-acting β2-agonists, long-acting muscarinic antagonist

Induction of MHC-mismatched Mouse Lung Allograft Acceptance with Combined Donor Bone Marrow: Lung Transplant using a 12-Hour Nonmyeloablative Conditioning Regimen

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Vulic, Ante; Panoskaltsis-Mortari, Angela; McDyer, John F.; Luznik, Leo

2016-01-01

Background Despite broad and intense conventional immunosuppression, long-term survival after lung transplantation lags behind that for other solid organ transplants, primarily because of allograft rejection. Therefore, new strategies to promote lung allograft acceptance are urgently needed. The purpose of the present study was to induce allograft tolerance with a protocol compatible with deceased donor organ utilization. Methods Using the MHC-mismatched mouse orthotopic lung transplant model, we investigated a conditioning regimen consisting of pretransplant T cell depletion, low dose total body irradiation and posttransplant (donor) bone marrow and splenocyte infusion followed by posttransplantation cyclophosphamide (PTTT-PTB/PTCy). Results Our results show that C57BL/6 recipients of BALB/c lung allografts undergoing this complete short-duration nonmyeloablative conditioning regimen had durable lung allograft acceptance. Mice that lacked 1 or more components of this regimen exhibited significant graft loss. Mechanistically, animals with lung allograft acceptance had established higher levels of donor chimerism, lymphocyte responses which were attenuated to donor antigens but maintained to third-party antigens, and clonal deletion of donor-reactive host Vβ T cells. Frequencies of Foxp3+ T regulatory cells were comparable in both surviving and rejected allografts implying that their perturbation was not a dominant cell-regulatory mechanism. Donor chimerism was indispensable for sustained tolerance, as evidenced by acute rejection of allografts in established chimeric recipients of PTTT-PTB/PTCy following a chimerism-ablating secondary recipient lymphocyte infusion. Conclusion Together, these data provide proof-of-concept for establishing lung allograft tolerance with tandem donor bone marrow transplantation (BMT) using a short-duration nonmyeloablative conditioning regimen and PTCy. PMID:27861294

A phase I/II trial of intensity modulated radiation (IMRT) dose escalation with concurrent fixed-dose rate gemcitabine (FDR-G) in patients with unresectable pancreatic cancer.

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Ben-Josef, Edgar; Schipper, Mathew; Francis, Isaac R; Hadley, Scott; Ten-Haken, Randall; Lawrence, Theodore; Normolle, Daniel; Simeone, Diane M; Sonnenday, Christopher; Abrams, Ross; Leslie, William; Khan, Gazala; Zalupski, Mark M

2012-12-01

Local failure in unresectable pancreatic cancer may contribute to death. We hypothesized that intensification of local therapy would improve local control and survival. The objectives were to determine the maximum tolerated radiation dose delivered by intensity modulated radiation with fixed-dose rate gemcitabine (FDR-G), freedom from local progression (FFLP), and overall survival (OS). Eligibility included pathologic confirmation of adenocarcinoma, radiographically unresectable, performance status of 0-2, absolute neutrophil count of ≥ 1,500/mm(3), platelets ≥ 100,000/mm(3), creatinine CRM (Time-to-Event Continual Reassessment Method) with the target dose-limiting toxicity (DLT) rate set to 0.25. Fifty patients were accrued. DLTs were observed in 11 patients: G3/4 anorexia, nausea, vomiting, and/or dehydration (7); duodenal bleed (3); duodenal perforation (1). The recommended dose is 55 Gy, producing a probability of DLT of 0.24. The 2-year FFLP is 59% (95% confidence interval [CI]: 32-79). Median and 2-year overall survival are 14.8 months (95% CI: 12.6-22.2) and 30% (95% CI 17-45). Twelve patients underwent resection (10 R0, 2 R1) and survived a median of 32 months. High-dose radiation therapy with concurrent FDR-G can be delivered safely. The encouraging efficacy data suggest that outcome may be improved in unresectable patients through intensification of local therapy. Copyright © 2012 Elsevier Inc. All rights reserved.

24-Hour Fetal/Maternal Monitoring System Based on Phonocardiogram Analysis

OpenAIRE

Zhdanov Dmitry; Bureev Artem; Kosteley Yana

2018-01-01

The article describes an engineering prototype of the Device for 24-hour monitoring over the functional state of the fetus and mother’s cardiovascular system in the antenatal period of pregnancy. The Device is a hardware and software system that ensures the registration and analysis of fetus and mother’s phonocardiograms with further processing and interpretation. The interpretation process is designed to timely detect conditions that constitute a threat to a fetus. The Device operates as par...

Comparison of two dose regimens of ibuprofen for the closure of patent ductus arteriosus in preterm newborns.

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Dornelles, Laura Vargas; Corso, Andréa Lúcia; Silveira, Rita de Cássia; Procianoy, Renato Soibelmann

2016-01-01

To compare the efficacy of intravenous ibuprofen at high (20-10-10mg/kg/dose) and low doses (10-5-5mg/kg/dose) the closure of patent ductus arteriosus in preterm newborns. A cohort study with historical control of newborns that received high- and low-dose intravenous ibuprofen, from 2010 to 2013 in a neonatal intensive care unit, for closure of the patent ductus arteriosus, documented by echocardiography. Secondary outcomes included the number of ibuprofen cycles, incidence of bronchopulmonary dysplasia, necrotizing enterocolitis, changes in renal function, and death. Seventy-seven patients received three doses of ibuprofen for the treatment of patent ductus arteriosus, with 33 receiving high-dose and 44 low-dose therapy. The ductus closed after the first cycle in 25 (56.8%) low-dose patients and in 17 (51.5%) high-dose patients (p>0.99). Sixteen patients received a second cycle of ibuprofen, and the ductus closed in 50% after low-dose and in 60% after high-dose therapy (p>0.99). Seven patients required surgery for ductus closure, 13.6% in the low-dose group and 3% in the high-dose group (p=0.22). Thirty-nine patients developed bronchopulmonary dysplasia, 50% in the low-dose group and 51.5% in the high-dose group (p>0.99). Twenty-two (50%) low-dose patients died vs. 15 (45.5%) high-dose patients (p=0.86). There was no difference in closure of the ductus arteriosus or occurrence of adverse effects between the two dose regimens. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Addition of Ceftriaxone and Amikacin to a Ciprofloxacin plus Metronidazole Regimen for Preventing Infectious Complications of Transrectal Ultrasound-Guided Prostate Biopsy: A Randomized Controlled Trial

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Mohammad-Hossein Izadpanahi

2017-01-01

Full Text Available Background. The objective of this study was to evaluate the efficacy of adding single doses of ceftriaxone and amikacin to a ciprofloxacin plus metronidazole regimen on the reduction of infectious complications following transrectal ultrasound-guided prostate biopsy (TRUS Bx. Materials and Methods. Four hundred and fifty patients who were candidates for TRUS Bx were divided into two groups of 225 each. The control group received ciprofloxacin 500 mg orally every 12 hours together with metronidazole 500 mg orally every 8 hours from the day prior to the procedure until the fifth postoperative day. In the second group, single doses of ceftriaxone 1 g by intravenous infusion and amikacin 5 mg/kg intramuscularly were administered 30–60 minutes before TRUS Bx in addition to the oral antimicrobials described for group 1. The incidence of infection was compared between the groups. Results. The incidence of infectious complications in the intervention group was significantly lower than that in the control group (4.6% versus 0.9%, p=0.017. Conclusion. The addition of single doses of intramuscular amikacin and intravenously infused ceftriaxone to our prophylactic regimen of ciprofloxacin plus metronidazole resulted in a statistically significant reduction of infectious complications following TRUS Bx.

Steady-State Serum T3 Concentrations for 48 Hours Following the Oral Administration of a Single Dose of 3,5,3'-Triiodothyronine Sulfate (T3S).

Science.gov (United States)

Santini, Ferruccio; Giannetti, Monica; Ricco, Ilaria; Querci, Giorgia; Saponati, Giorgio; Bokor, Daniela; Rivolta, Giovanni; Bussi, Simona; Braverman, Lewis E; Vitti, Paolo; Pinchera, Aldo

2014-07-01

Sulfate conjugation of thyroid hormones is an alternate metabolic pathway that facilitates the biliary and urinary excretion of iodothyronines and enhances their deiodination rate, leading to the generation of inactive metabolites. A desulfating pathway reverses this process, and thyromimetic effects have been observed following the parenteral administration of 3,5,3'-triiodothyronine (T3) sulfate (T3S) in rats. The present study investigated whether T3S is absorbed after oral administration in humans and if it represents a source of T3. Twenty-eight hypothyroid patients (7 men and 21 women; mean age, 44 ± 11 years) who had a thyroidectomy for thyroid carcinoma were enrolled. Replacement thyroid hormone therapy was withdrawn (42 days for thyroxine, 14 days for T3) prior to 131I remnant ablation. A single oral dose of 20, 40, 80 (4 patients/group), or 160 μg (16 patients/group) of T3S was administered 3 days before the planned administration of 131I. Blood samples for serum T3S and total T3 (TT3) concentrations were obtained at various times up to 48 hours after T3S administration. At all T3S doses, serum T3S concentrations increased, reaching a peak at 2 to 4 hours and progressively returning to basal levels within 8 to 24 hours. The T3S maximum concentration (Cmax) and area under the 0- to 48-hour concentration-time curve (AUC0-48h) were directly and significantly related to the administered dose. An increase in serum TT3 concentration was observed (significant after 1 hour), and the concentration increased further at 2 and 4 hours and then remained steady up to 48 hours after T3S administration. There was a significant direct correlation between the TT3 AUC0-48h and the administered dose of T3S. No changes in serum free thyroxine (T4) concentrations during the entire study period were observed, whereas serum thyroid-stimulating hormone levels increased slightly at 48 hours, but this was not related to the dose of T3S. No adverse events were reported. (1) T3S is

Microleakage of two self-adhesive cements in the enamel and dentin after 24 hours and two months.

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Zahra Jaberi Ansari

2014-08-01

Full Text Available Microleakage is a main cause of restorative treatment failure. In this study, we compared occlusal and cervical microleakage of two self-adhesive cements after 24 hours and two months.In this in-vitro experimental study, class II inlay cavities were prepared on 60 sound human third molars. Composite inlays were fabricated with Z100 composite resin. The teeth were randomly assigned to six groups. RelyX-Arc (control, RelyX-Unicem and Maxcem were used for the first three groups and specimens were stored in distilled water at 37°C for 24 hours. The same cements were used for the remaining three groups, but the specimens were stored for 2 months. The teeth were subjected to 500 thermal cycles (5°C and 55°C and immersed in 0.5% basic fuchsin for 24 hours and then sectioned mesiodistally and dye penetration was evaluated in a class II cavity with occlusal and cervical margins using X20 magnification stereomicroscope. Data were analyzed using Kruskal Wallis and Mann-Whitney U tests.After 24 hours, cements had significant differences only in cervical margin microleakage (P=0.0001 and microleakage of RelyX-Unicem and Maxcem was significantly more than that of RelyX-Arc (both P=0.0001. Cervical microleakage in RelyX-Unicem and Maxcem was greater than occlusal (P=0.0001 and P=0.001, respectively. Microleakage was not significantly different between the occlusal and cervical margins after 2 months.Cervical microleakage was greater than occlusal in RelyX-Unicem and Maxcem after 24h. The greatest microleakage was reported for the cervical margin of RelyX-Unicem after 24 hours.

Current regimen of pulse therapy for pemphigus: Minor modifications, improved results

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Pasricha J

2008-01-01

Full Text Available Background: If administered properly, dexamethasone cyclophosphamide pulse (DCP therapy has the potential to effect lifelong recovery from pemphigus. Aims: The objective of this paper is to highlight various parameters of DCP therapy and also, to report the effects of a few modifications in the regimen. Methods: An analysis of 123 patients treated with the DCP/DP regimen over a period of five years (1998 to 2002 is presented here. Seventeen patients who did not start/continue the treatment and three patients who died during the treatment have been excluded from the analysis. Twenty patients who had not yet started families were given only dexamethasone pulses (DPs while 103 patients received DCPs. Low dose (50 mg/day cyclophosphamide was used as in the standard regimen. The three modifications introduced into the regimen were: (1 an additional daily dose of oral betamethasone sufficient to control the disease activity during phase I, which was progressively tapered off completely as the patient recovered, (2 use of systemic antibiotics if the patient had skin lesions, and oral anti-candida drugs if the patient had oral ulcers until complete healing, and (3 insistence on thorough cleaning of the skin and scalp with a normal soap and shampoo, and proper maintenance of oral hygiene in spite of skin/mucosal lesions. The regimen consisted of DCP/DP repeated in exactly 28-day cycles, along with 50 mg cyclophosphamide per day, insistence on completing the treatment and avoiding irregular pulses in all patients. The number of DCPs/DPs during phase I varied in different patients depending upon the dose of betamethasone used and the rate of recovery, but phase II (nine DCPs/DPs in exactly 28-day cycles along with 50 mg cyclophosphamide per day and phase III (only 50 mg cyclophosphamide per day was fixed at nine months each. This was followed by posttreatment follow-up (phase IV. Results: At present, all the patients are in complete remission. The

Efficacy and Safety of a Colistin Loading Dose, High-Dose Maintenance Regimen in Critically Ill Patients With Multidrug-Resistant Gram-Negative Pneumonia.

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Elefritz, Jessica L; Bauer, Karri A; Jones, Christian; Mangino, Julie E; Porter, Kyle; Murphy, Claire V

2017-09-01

Emergence of multidrug-resistant (MDR) gram-negative (GN) pathogens and lack of novel antibiotics have increased the use of colistin, despite unknown optimal dosing. This study aimed to evaluate the safety and efficacy of a colistin loading dose, high-dose (LDHD) maintenance regimen in patients with MDR-GN pneumonia. A retrospective cohort analysis was performed comparing critically ill patients with MDR-GN pneumonia pre- and postimplementation of a colistin LDHD guideline with a primary outcome of clinical cure. Safety was assessed using incidence of acute kidney injury (AKI) based on RIFLE (risk, injury, failure, loss, end-stage renal disease) criteria. Seventy-two patients met the inclusion criteria (42 preimplementation and 30 postimplementation). Clinical cure was achieved in 23 (55%) patients in the preimplementation group and 20 (67%) patients in the postimplementation group ( P = .31). AKI occurred in 50% of the patients during the preimplementation period and 58% during the postimplementation period ( P = .59) with no difference in initiation rates of renal replacement therapy. The increased clinical cure rate after implementation of the colistin LDHD guideline did not reach statistical significance. The LDHD guideline, however, was not associated with an increased incidence of AKI, despite higher intravenous colistin doses. Opportunity exists to optimize colistin dosage while balancing toxicity, but larger studies are warranted.

Optimization of urinary dipstick pH: Are multiple dipstick pH readings reliably comparable to commercial 24-hour urinary pH?

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Abbott, Joel E; Miller, Daniel L; Shi, William; Wenzler, David; Elkhoury, Fuad F; Patel, Nishant D; Sur, Roger L

2017-09-01

Accurate measurement of pH is necessary to guide medical management of nephrolithiasis. Urinary dipsticks offer a convenient method to measure pH, but prior studies have only assessed the accuracy of a single, spot dipstick. Given the known diurnal variation in pH, a single dipstick pH is unlikely to reflect the average daily urinary pH. Our goal was to determine whether multiple dipstick pH readings would be reliably comparable to pH from a 24-hour urine analysis. Kidney stone patients undergoing a 24-hour urine collection were enrolled and took images of dipsticks from their first 3 voids concurrently with the 24-hour collection. Images were sent to and read by a study investigator. The individual and mean pH from the dipsticks were compared to the 24-hour urine pH and considered to be accurate if the dipstick readings were within 0.5 of the 24-hour urine pH. The Bland-Altman test of agreement was used to further compare dipstick pH relative to 24-hour urine pH. Fifty-nine percent of patients had mean urinary pH values within 0.5 pH units of their 24-hour urine pH. Bland-Altman analysis showed a mean difference between dipstick pH and 24-hour urine pH of -0.22, with an upper limit of agreement of 1.02 (95% confidence interval [CI], 0.45-1.59) and a lower limit of agreement of -1.47 (95% CI, -2.04 to -0.90). We concluded that urinary dipstick based pH measurement lacks the precision required to guide medical management of nephrolithiasis and physicians should use 24-hour urine analysis to base their metabolic therapy.

Effects of dietary interventions on 24-hour urine parameters in patients with idiopathic recurrent calcium oxalate stones

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Mustafa Kıraç

2013-02-01

Full Text Available The aim of this study is to investigate the effects of dietary factors on 24-hour urine parameters in patients with idiopathic recurrent calcium oxalate stones. A total of 108 of idiopathic recurrent calcium oxalate stones were included in the study. A 24-hour urinalysis was performed and metabolic abnormalities were measured for all of the patients. All of the patients were given specialized diets for their 24-hour urine abnormalities. At the end of first month, the same parameters were examined in another 24-hour urinalysis. Hyperoxaluria, hypernatruria, and hypercalciuria were found in 84 (77%, 43 (39.8%, and 38 (35.5% of the patients, respectively. The differences between the oxalate, sodium, volume, uric acid, and citrate parameters before and after the dietary intervention were significant (p < 0.05. The calcium parameters were not significantly different before and after the intervention. We found that oxalate, sodium, volume, uric acid, and citrate—but not calcium—abnormalities in patients with recurrent calcium oxalate stones can be corrected by diet. The metabolic profiles of idiopathic calcium oxalate stone patients should be evaluated and the appropriate dietary interventions should be implemented to decrease stone recurrence.

Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with cisplatin therapy: randomized, double-blind study protocol--EASE

DEFF Research Database (Denmark)

Grunberg, Steven; Chua, Daniel; Maru, Anish

2011-01-01

multiple-day NK1RA administration. Preliminary data suggested that single-dose aprepitant before chemotherapy could provide CINV protection throughout the overall risk phase (OP; 0 to 120 hours). This study compared a 3-day oral aprepitant schedule to a regimen containing a single dose of the intravenous...

Improvement of Endovascular Stroke Treatment: A 24-Hour Neuroradiological On-Site Service Is Not Enough

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Omid Nikoubashman

2018-01-01

Full Text Available Background and Purpose. With the advent of endovascular stroke treatment (EST with mechanical thrombectomy, stroke treatment has also become more challenging. Purpose of this study was to investigate whether a fulltime neuroradiological on-site service and workflow optimization with a structured documentation of the interdisciplinary stroke workflow resulted in improved procedural times. Material and Methods. Procedural times of 322 consecutive patients, who received EST (1 before (n=96 and (2 after (n=126 establishing a 24-hour neuroradiological on-site service as well as (3 after implementation of a structured interdisciplinary workflow documentation (“Stroke Check” (n=100, were analysed. Results. A fulltime neuroradiological on-site service resulted in a nonsignificant improvement of procedural times during out-of-hours admissions (p≥0.204. Working hours and out-of-hours procedural times improved significantly, if additional workflow optimization was realized (p≤0.026. Conclusions. A 24-hour interventional on-site service is a major prerequisite to adequately provide modern reperfusion therapies in patients with acute ischemic stroke. However, simple measures like standardized and focused documentation that affect the entire interdisciplinary pre- and intrahospital stroke rescue chain seem to be important.

Meeting new Canadian 24-Hour Movement Guidelines for the Early Years and associations with adiposity among toddlers living in Edmonton, Canada.

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Lee, Eun-Young; Hesketh, Kylie D; Hunter, Stephen; Kuzik, Nicholas; Rhodes, Ryan E; Rinaldi, Christina M; Spence, John C; Carson, Valerie

2017-11-20

the findings of this study, identifying modifiable correlates of screen time to inform appropriate strategies to reduce screen time appears key for increasing the proportion of toddlers meeting the 24-Hour Movement Guidelines for the Early Years. Future research should examine the associations between meeting the new guidelines and other health indicators. Furthermore, future high-quality studies examining dose-response relationships between movement behaviours and health indicators are needed to inform guideline updates.

Relationship between 24- hour Holter variables, chest discomfort and syncope: Does age matter?

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Samir Kanti Saha

2013-01-01

Full Text Available One hundred and forty four ambulatory, non-emergent human subjects from 20-88 years of age were investigated following routine 24 hour Holter monitoring referred by primary and tertiary care centers primarily for evaluation of palpitations and syncope. The patients were grouped into 3 different age categories: A 20-59 years of age (16%, B 60-69 years of age (26.4% and C > 70 years of age (57.6%. Heart rate profile, RR intervals, symptoms, frequency of premature supra ventricular and ventricular complexes were registered. The data show that though the occurrence and frequency of premature atrial and ventricular contractions over a period of 24 hours did not differ between the groups, the younger subjects documented more subjective discomforts during the Holter monitoring. Extra-systoles in excess of 1000 beats / 24 hour occured incessantly throughout the registration. Patients with syncope and those without did not differ as regards the Holter variables. However, subjects with atrial fibrillation had acceptable rate control and had significantly lower incidence of syncope than those with sinus rhythm. The findings suggest that in a county setting, Holter monitoring for evaluation of syncope may not be the first hand mode of investigation in a non emergent setting. On the contrary, the modality appears to be valuable for monitoring patients with atrial fibrillation. Even mild symptoms in the elderly population may warrant closer clinical follow up to prevent cardiac events and/or syncope leading to serious physical injury.

Impact of renal denervation on 24-hour ambulatory blood pressure: results from SYMPLICITY HTN-3.

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Bakris, George L; Townsend, Raymond R; Liu, Minglei; Cohen, Sidney A; D'Agostino, Ralph; Flack, John M; Kandzari, David E; Katzen, Barry T; Leon, Martin B; Mauri, Laura; Negoita, Manuela; O'Neill, William W; Oparil, Suzanne; Rocha-Singh, Krishna; Bhatt, Deepak L

2014-09-16

Prior studies of catheter-based renal artery denervation have not systematically performed ambulatory blood pressure monitoring (ABPM) to assess the efficacy of the procedure. SYMPLICITY HTN-3 (Renal Denervation in Patients With Uncontrolled Hypertension) was a prospective, blinded, randomized, sham-controlled trial. The current analysis details the effect of renal denervation or a sham procedure on ABPM measurements 6 months post-randomization. Patients with resistant hypertension were randomized 2:1 to renal denervation or sham control. Patients were on a stable antihypertensive regimen including maximally tolerated doses of at least 3 drugs including a diuretic before randomization. The powered secondary efficacy endpoint was a change in mean 24-h ambulatory systolic blood pressure (SBP). Nondipper to dipper (nighttime blood pressure [BP] 10% to 20% lower than daytime BP) conversion was calculated at 6 months. The 24-h ambulatory SBP changed -6.8 ± 15.1 mm Hg in the denervation group and -4.8 ± 17.3 mm Hg in the sham group: difference of -2.0 mm Hg (95% confidence interval [CI]: -5.0 to 1.1; p = 0.98 with a 2 mm Hg superiority margin). The daytime ambulatory SBP change difference between groups was -1.1 (95% CI: -4.3 to 2.2; p = 0.52). The nocturnal ambulatory SBP change difference between groups was -3.3 (95 CI: -6.7 to 0.1; p = 0.06). The percent of nondippers converted to dippers was 21.2% in the denervation group and 15.0% in the sham group (95% CI: -3.8% to 16.2%; p = 0.30). Change in 24-h heart rate was -1.4 ± 7.4 in the denervation group and -1.3 ± 7.3 in the sham group; (95% CI: -1.5 to 1.4; p = 0.94). This trial did not demonstrate a benefit of renal artery denervation on reduction in ambulatory BP in either the 24-h or day and night periods compared with sham (Renal Denervation in Patients With Uncontrolled Hypertension [SYMPLICITY HTN-3]; NCT01418261). Copyright © 2014 American College of Cardiology Foundation. Published by

Leveraging protein binding and the EPR effect in legacy chemotherapy regimens

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Shireesh Apte

2016-12-01

Full Text Available Legacy chemotherapy regimens have the potential to be significantly more effective and less toxic if the dosage is titrated so that the mole ratio of drugs to circulating albumin is less than or equal to 1 and the order of administration of the drugs within each course of the regimen follows the sequence most hydrophobic (usually the least dose to least hydrophobic (usually the largest dose

Relationship Between 24-Hour Ambulatory Blood Pressure and Cognitive Function in Community-Living Older Adults: The UCSD Ambulatory Blood Pressure Study.

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Conway, Kyle S; Forbang, Nketi; Beben, Tomasz; Criqui, Michael H; Ix, Joachim H; Rifkin, Dena E

2015-12-01

Twenty-four-hour ambulatory blood pressure (BP) patterns have been associated with diminished cognitive function in hypertensive and very elderly populations. The relationship between ambulatory BP patterns and cognitive function in community-living older adults is unknown. We conducted a cross-sectional study in which 24-hour ambulatory BP, in-clinic BP, and cognitive function measures were obtained from 319 community-living older adults. The mean age was 72 years, 66% were female, and 13% were African-American. We performed linear regression with performance on the Montreal Cognitive Assessment (MoCA) as the primary outcome and 24-hour BP patterns as the independent variable, adjusting for age, sex, race/ethnicity, education, and comorbidities. Greater nighttime systolic dipping (P = 0.046) and higher 24-hour diastolic BP (DBP; P = 0.015) were both significantly associated with better cognitive function, whereas 24-hour systolic BP (SBP), average real variability, and ambulatory arterial stiffness were not. Higher 24-hour DBP and greater nighttime systolic dipping were significantly associated with improved cognitive function. Future studies should examine whether low 24-hour DBP and lack of nighttime systolic dipping predict future cognitive impairment. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Role of redistribution and 24 hour reinjection images to assess myocardial viability in patients with acute myocardial infarction

International Nuclear Information System (INIS)

Yoon, Seok Nam; Pai, Moon Sun; Park, Chan H.; Yoon, Myung Ho; Choi, Byung Il

1998-01-01

We evaluated the importance of redistribution and 24 hour reinjection images in Tl-201 SPECT assessment of myocardial viability after acute myocardial infarction (AMI). We performed dipyridamole stress-4 hour redistribution-24 hour reinjection Tl-201 SPECT in 43 patients with recent AMI (4-16 days). The myocardium was divided into 16 segments and perfusion grade was measured visually with 4 point score from 0 to 3 (absent uptake to normal uptake). A perfusion defect with stress score 2 was considered moderate. A defect was considered severe if the stress score was 0 or 1 (absent uptake or severe perfusion decrease). Moderate defect on stress image were considered viable and and segments with severe defect were considered viable if they showed improvement of 1 score or more on redistribution or reinjection images. We compared the results of viability assessment in stress-redistribution and stress-reinjection images. On visual analysis, 344 of 688 segments (50%) had abnormal perfusion. Fify two (15%) had moderate perfusion defects and 292 (85%) had severe perfusion defects on stress image. Of 292 severe stress defects, 53 were irreversible on redistribution and reversible on reinjection images, and 15 were reverseble on redistribution and irreversible on reinjection images. Two hundred twenty four of 292 segments (76.7%) showed concordant results on stress-redistribution and stress- reinjection images. Therefore 24 hour reinjection image changed viability status from necrotic to viable in 53 segments of 292 severe stress defect (18%). However, myocardial viability was underestimated in only 5% (15/292) of severe defects by 24 hour reinjection. The 24 hour reinjection imaging is useful in the assessment of myocardial viability. It is more sensitive than 4 hour redistribution imaging. However, both redistribution and reinjection images are needed since they complement each other

Fixed-dose combinations of antimicrobials: A need for special attention

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N Shafiq

2016-01-01

Full Text Available Objective: To highlight the issue of freely available fixed-dose combinations (FDCs of antimicrobials. Methods: A critique of two such antimicrobial FDCs was undertaken wherein the following aspects were assessed - rational and regulatory issues and justification for clinical use. Available in vitro, in vivo (animals and humans evidence from published literature was analysed. Conclusions: There are several inadequately addressed aspects of the considered FDCs which are available in Indian market. In view of the growing problem of antimicrobial resistance, this issue must get the required attention.

Predicting Patients with Inadequate 24- or 48-Hour Urine Collections at Time of Metabolic Stone Evaluation.

Science.gov (United States)

McGuire, Barry B; Bhanji, Yasin; Sharma, Vidit; Frainey, Brendan T; McClean, Megan; Dong, Caroline; Rimar, Kalen; Perry, Kent T; Nadler, Robert B

2015-06-01

We aimed to understand the characteristics of patients who are less likely to submit adequate urine collections at metabolic stone evaluation. Inadequate urine collection was defined using two definitions: (1) Reference ranges for 24-hour creatinine/kilogram (Cr/24) and (2) discrepancy in total 24-hour urine Cr between 24-hour urine collections. There were 1502 patients with ≥1 kidney stone between 1998 and 2014 who performed a 24- or 48-hour urine collection at Northwestern Memorial Hospital and who were identified retrospectively. Multivariate analysis was performed to analyze predictor variables for adequate urine collection. A total of 2852 urine collections were analyzed. Mean age for males was 54.4 years (range 17-86), and for females was 50.2 years (range 8-90). One patient in the study was younger than 17 years old. (1) Analysis based on the Cr 24/kg definition: There were 50.7% of patients who supplied an inadequate sample. Females were nearly 50% less likely to supply an adequate sample compared with men, Pcollections were achieved in 82.8%, 66.9%, 51.7%, 38.5%, and 26.4% of patients, respectively. Statistical significance was observed based on differences of ≥40%, and this was defined as the threshold for an inadequate sample. Female sex (OR 0.73 [0.54-0.98], P=0.037) predicted supplying inadequate samples. Adequate collections were more likely to be received on a Sunday (OR 1.6 [1.03-2.58], P=0.038) and by sedentary workers (OR 2.3 [1.12-4.72], P=0.023). Urine collections from patients during metabolic evaluation for nephrolithiasis may be considered inadequate based on two commonly used clinical definitions. This may have therapeutic or economic ramifications and the propensity for females to supply inadequate samples should be investigated further.

Radioiodine treatment for complicated hyperthyroidism using a fixed dose regime

International Nuclear Information System (INIS)

Paul, A.K.; Rahman, S.H.; Ansari, S.M.

2005-01-01

Full text: Hyperthyroidism in the elderly and all those with cardiovascular and psychiatric problem has increased mortality and morbidity rate. These patients need special care to cure the disease promptly and permanently for avoidance of complications. Radioactive I-131 is one of the accepted forms of treatment for hyperthyroidism and increasingly being considered for the patients in whom rapid and permanent control of disease is desirable. To evaluate the success of I-131 to cure disease in-patients with complicated hyperthyroidism, we prospectively studied the outcome of radioiodine therapy using a fixed dose regime. Ninety-three patients with toxic diffuse goitre (65 female, 28 male) age ranging from 29-67 years (mean ? SD 41.35 ? 11.02 years) were evaluated. The subjects included 71 cases with cardiovascular problem, 13 elderly patients, 5 with poor drug compliance and 4 with associated psychiatric disease. The individual was excluded from the study who had autonomous toxic nodule. Every patient was pre-treated with antithyroid drugs for 4 weeks and the drug was discontinued for 3 days before administering I-131. No patients had post-treatment antithyroid drugs. All the patients were treated with a fixed oral dose of 15 mCi I-131 sodium iodide. Post-treatment follow-up examinations were done at 6 weeks without biochemical tests, at 3 months, 6 months, 9 months and 1 year and then annually with biochemical tests. Patients were classified as cured if the biochemical status was either euthyroid or hypothyroid at one year without further treatment by antithyroid drugs or radioiodine. Of the 93 cases, 82 patients became euthyroid or hypothyroid requiring no further treatment for hyperthyroidism with an overall cure of 88.17%. Hypothyroidism was developed in 49 (52.69%) patients at one year of whom 39 became hypothyroid within 6 months and another 10 patients within 1 year. 4 patients were subclinical hyperthyroid at 6 months and still hyperthyroid at 9 months. 7

[Comparison of dietary survey, frequency and 24 hour urinary Na methods in evaluation of salt intake in the population].

Science.gov (United States)

Li, Jianhong; Lu, Zilong; Yan, Liuxia; Zhang, Jiyu; Tang, Junli; Cai, Xiaoning; Guo, Xiaolei; Ma, Jixiang; Xu, Aiqiang

2014-12-01

To compare the difference and correlation between dietary salt intakes assessed by 24 hours urinary Na method, food weighted record method and food frequency questionnaire method. All 2 184 subjects aged 18 to 69 were selected by multi stage stratified cluster random sampling method in Shandong province in June to September, 2011. Dietary salt intakes were measured by 24 hours urinary Na method, food weighted record method and food frequency questionnaire method. The information on gender, age, dining locations and labour intensity of members dining at home for 3 days were recorded. And the dietary habits were surveyed by questionnaire. Salt intakes were 14.0, 12.0 and 10.5 g/d assessed by 24 hours urinary Na method, food weighted record method and food frequency questionnaire, respectively. Comparing with 24 hours urinary Na method, salt intakes assessed by food weighted record method and food frequency questionnaire method were 2.0 g (14.3% undervalued) and 3.4 g (24.3% undervalued) less, respectively. Comparing with 24 hours urinary Na method, the proportion of individuals with salt intake over-reported and under-reported were 42.4% (856/2 020) and 55.3% (1 117/2 020) by food weighted record method, and were 20.7% (418/2 020) and 16.3% (329/2 020) by food frequency questionnaire method, respectively; the proportion of individuals with salt intakes within ± 25% of 24 hours urinary Na method were 36.9% (745/2 020) and 28.4% (574/2 020), respectively. Salt intakes assessed by 24 hours urinary method correlated significantly with both salt intakes assessed by food weighted record method and food frequency questionnaire method; the correlation coefficients were 0.13 and 0.07, respectively. With the increasing of salt intakes by subjects' self-judgment, salt intakes were all rising significantly using three survey methods. Salt intakes of three group population of light, moderate and partial taste salty were 13.6, 13.6 and 14.7 g/d by 24 hours urinary Na method (F

Three day oral course of Augmentin to treat chancroid.

Science.gov (United States)

Ndinya-Achola, J O; Nsanze, H; Karasira, P; Fransen, L; D'Costa, L J; Piot, P; Ronald, A R

1986-01-01

Amoxycillin and clavulanic acid (Augmentin; Beecham Research Laboratories) was used to treat patients with bacteriologically proved chancroid in three different dose regimens. A single dose of Augmentin (amoxycillin 3 g, clavulanic acid 350 mg) was found to be ineffective. A similar dose repeated after 24 hours was equally ineffective, but a dose (amoxycillin 500 mg, clavulanic acid 250 mg) given every 8 hours for three days was found to be effective. The drug was well tolerated and no side effects were noted in any of the patients treated. PMID:3733082

Fixed-dose combinations at the front line of multimodal pain management: perspective of the nurse-prescriber

Directory of Open Access Journals (Sweden)

O'Brien J

2013-02-01

Full Text Available Joanne O’Brien,1 Joseph V Pergolizzi Jr,2 Mart van de Laar3, Hans-Ulrich Mellinghoff,4 Ignacio Morón Merchante,5 Srinivas Nalamachu,6 Serge Perrot,7 Robert B Raffa81Department of Pain Medicine, Beaumont Hospital, Beaumont, Dublin, Ireland; 2Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Association of Chronic Pain Patients, Houston, TX; Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, USA; 3Arthritis Center Twente, Enschede, The Netherlands; 4Department of Endocrinology, Diabetology and Osteology, Kantonsspital St Gallen, Switzerland; 5Centro de Salud Universitario Goya, Madrid, Spain; 6Kansas University Medical Center, Kansas City, and International Clinic Research, Leawood, KS, USA; 7Service de Médecine Interne et Consultation de la Douleur, Hôpital Hotel Dieu, Paris Descartes University, Paris, France; 8Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia PA, USAAbstract: Pain should be treated promptly and effectively to restore the patient to full function, avoid pain chronification, and preserve quality of life. A recent pain specialists' meeting discussed the use of different pharmacological treatment options, such as topical analgesics, nonopioid agents (such as paracetamol and nonsteroidal anti-inflammatory drugs, weak and strong opioids, and fixed-dose combination products in the management of moderate to severe pain from different etiologies. One of the topics discussed in, and subsequent to, this meeting was the role of fixed-dose combination products for nurse-prescribers who are in many ways at the front line of managing both acute and chronic pain syndromes. The panel agreed that proper product selection should take into account the patient's age, condition, type of pain, and comorbidities, as well as balance safety with effectiveness. Although nurse-prescribers need to be aware of cumulative paracetamol dosing, fixed-dose

Number of 24-hour diet recalls needed to estimate energy intake.

Science.gov (United States)

Ma, Yunsheng; Olendzki, Barbara C; Pagoto, Sherry L; Hurley, Thomas G; Magner, Robert P; Ockene, Ira S; Schneider, Kristin L; Merriam, Philip A; Hébert, James R

2009-08-01

Twenty-four-hour diet recall interviews (24HRs) are used to assess diet and to validate other diet assessment instruments. Therefore it is important to know how many 24HRs are required to describe an individual's intake. Seventy-nine middle-aged white women completed seven 24HRs over a 14-day period, during which energy expenditure (EE) was determined by the doubly labeled water method (DLW). Mean daily intakes were compared to DLW-derived EE using paired t tests. Linear mixed models were used to evaluate the effect of call sequence and day of the week on 24HR-derived energy intake while adjusting for education, relative body weight, social desirability, and an interaction between call sequence and social desirability. Mean EE from DLW was 2115 kcal/day. Adjusted 24HR-derived energy intake was lowest at call 1 (1501 kcal/day); significantly higher energy intake was observed at calls 2 and 3 (2246 and 2315 kcal/day, respectively). Energy intake on Friday was significantly lower than on Sunday. Averaging energy intake from the first two calls better approximated true energy expenditure than did the first call, and averaging the first three calls further improved the estimate (p=0.02 for both comparisons). Additional calls did not improve estimation. Energy intake is underreported on the first 24HR. Three 24HRs appear optimal for estimating energy intake.

[Combination of busulfan with increased-dose of fludarabine as conditioning regimen for MDS and MDS-AML patients with allo-HSCT].

Science.gov (United States)

Yuan, Jing; Ren, Hanyun; Qiu, Zhixiang; Li, Yuan; Wang, Mangju; Liu, Wei; Xu, Weilin; Sun, Yuhua; Wang, Lihong; Liang, Zeyin; Dong, Yujun; Ou, Jinping; Wang, Wensheng; Yin, Yue; Cen, Xinan; Wang, Qian

2015-06-01

To investigate the safety and efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for myelodysplastic syndrome (MDS) and secondary acute myelogenous leukemia (MDS-AML) using conditioning regimen with busulfan (Bu) and increased-dose of fludarabine (ID-Flu). A total of 49 patients with MDS or MDS-AML were treated by allo-HSCT, the clinical data was analyzed retrospectively. All patients achieved hematopoietic reconstitution. Neutrophil engraftment was at 10 - 22 days (median 13 days), and platelet engraftment was at 8 - 66 days (median 16 days). The cumulative incidences of Ⅱ-Ⅳ degree acute graft-versus-host disease (GVHD), hemorrhagic cystitis (HC), and hepatic venous occlusive disease (VOD) were 28.6%, 14.3% and 2.0%, respectively. The transplant-related mortality (TRM) was only 4.1% at 100d and 8.2% at 1-92 months of followed-up (median 14 months) period. Overall survival (OS) and disease free survival (DFS) was 75.5%, 73.5%, respectively. Kaplan-Meier curve showed that 3-year OS and 3-year DFS was (71.1 ± 7.8)%, (66.7 ± 8.3)%, respectively, with a relapse incidence (RI) 16.3%. OS for MDS and MDS-AML was 81.5% and 68.2%, and RI in two settings was 3.7%, 31.8%, respectively. OS for MDS-AML at complete remission (CR) and non-CR subgroup was 83.3% and 50.0%, respectively, while cumulative RR was 16.7% and 50.0%, respectively. OS and RI except for non-CR subgroup were 82.1% and 7.7%. Univariate analysis showed that pre-HSCT disease status had correlation with OS (P=0.031), but age, decitabine in conditioning regimen, stem cell source, HLA matching, patient-donor gender, dose of mononuclear cells and GVHD had no correlation with OS. Bu/ID-Flu conditioning regimen for MDS and MDS-AML has high efficiency, fewer complications, lower toxicity and TRM. The OS and DFS were higher and RI was lower except for refractory MDS-AML patients. The regimen is valuable for clinical application.

Single point estimation of phenytoin dosing: a reappraisal.

Science.gov (United States)

Koup, J R; Gibaldi, M; Godolphin, W

1981-11-01

A previously proposed method for estimation of phenytoin dosing requirement using a single serum sample obtained 24 hours after intravenous loading dose (18 mg/Kg) has been re-evaluated. Using more realistic values for the volume of distribution of phenytoin (0.4 to 1.2 L/Kg), simulations indicate that the proposed method will fail to consistently predict dosage requirements. Additional simulations indicate that two samples obtained during the 24 hour interval following the iv loading dose could be used to more reliably predict phenytoin dose requirement. Because of the nonlinear relationship which exists between phenytoin dose administration rate (RO) and the mean steady state serum concentration (CSS), small errors in prediction of the required RO result in much larger errors in CSS.

Attempt Quit Smoking 24+ Hours Maps and Data of Model-Based Small Area Estimates - Small Area Estimates

Science.gov (United States)

Attempt Quit Smoking 24+ Hours is defined as a person 18 years of age or older who must have reported smoking at least 100 cigarettes in his/her life, and now does not smoke at all but it has been less than 365 days since completely stopped smoking cigarettes, or now smoke everyday or some days but reported that have made attempt of quitting for more than 24 hours in the past 12 months.

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

OpenAIRE

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

2010-01-01

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

Serum thyroxine concentrations following fixed-dose radioactive iodine treatment in hyperthyroid cats: 62 cases (1986-1989)

International Nuclear Information System (INIS)

Meric, S.M.; Rubin, S.I.

1990-01-01

The medical records of 62 hyperthyroid cats treated with a fixed dose of 4 mCi of radioactive iodine (131I) were reviewed. In 60 cats, serum thyroxine concentrations were determined after treatment, allowing evaluation of treatment success. Eighty-four percent of the cats had normal serum thyroxine concentrations after treatment. Five of the 60 cats (8%) remained hyperthyroxinemic after treatment. Five cats (8%) were hypothyroxinemic when evaluated within 60 days of treatment. Three of these cats had normal serum thyroxine concentrations 6 months after treatment, and none had clinical signs of hypothyroidism. The administration of a fixed dose of 4 mCi of 131I was determined to be an effective treatment for feline hyperthyroidism

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

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

2015-10-01

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

Asthma Control Can Be Maintained after Fixed-Dose, Budesonide/Formoterol Combination Inhaler Therapy is Stepped Down from Medium to Low Dose

Directory of Open Access Journals (Sweden)

Masayuki Hojo

2013-01-01

Conclusions: If complete control of asthma, not only of clinical symptoms but also airway inflammation, is achieved by 3-6 months of fixed-dose budesonide/formoterol 4 puffs/day, it should be possible to safely perform step-down to 2 puffs/day.

Does aerobic exercise increase 24-hour ambulatory blood pressure among workers with high occupational physical activity? - A RCT

DEFF Research Database (Denmark)

Korshøj, Mette; Krause, Niklas; Clays, Els

2017-01-01

.9–3.8). Cleaners with high aerobic workload exhibited particularly high 24-hour ABP increases: systolic 6.0 mm Hg (95% CI 2.4–9.6), and diastolic 3.8 mm Hg (95% CI 1.3–6.4). CONCLUSION Aerobic exercise increased 24-hour ABP among cleaners. This adverse effect raises questions about the safety and intended benefits......OBJECTIVE High occupational physical activity (OPA) increases cardiovascular risk and aerobic exercise has been recommended for reducing this risk. This paper investigates the effects of an aerobic exercise intervention on 24-hour ambulatory blood pressure (ABP) among cleaners with high OPA....... METHODS Hundred and sixteen cleaners between 18 and 65 years were randomized. During the 4-month intervention period, the aerobic exercise group (AE) (n = 57) performed worksite aerobic exercise (2 × 30 minutes/week), while the reference group (REF) (n = 59) attended lectures. Between-group differences...

Does Aerobic Exercise Increase 24-Hour Ambulatory Blood Pressure Among Workers With High Occupational Physical Activity? - A RCT

DEFF Research Database (Denmark)

Korshøj, Mette; Krause, Niklas; Clays, Els

2017-01-01

.9–3.8). Cleaners with high aerobic workload exhibited particularly high 24-hour ABP increases: systolic 6.0 mm Hg (95% CI 2.4–9.6), and diastolic 3.8 mm Hg (95% CI 1.3–6.4). CONCLUSION Aerobic exercise increased 24-hour ABP among cleaners. This adverse effect raises questions about the safety and intended benefits......OBJECTIVE High occupational physical activity (OPA) increases cardiovascular risk and aerobic exercise has been recommended for reducing this risk. This paper investigates the effects of an aerobic exercise intervention on 24-hour ambulatory blood pressure (ABP) among cleaners with high OPA....... METHODS Hundred and sixteen cleaners between 18 and 65 years were randomized. During the 4-month intervention period, the aerobic exercise group (AE) (n = 57) performed worksite aerobic exercise (2 × 30 minutes/week), while the reference group (REF) (n = 59) attended lectures. Between-group differences...

Platelet aggregation according to body mass index in patients undergoing coronary stenting: should clopidogrel loading-dose be weight adjusted?

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Angiolillo, Dominick J; Fernández-Ortiz, Antonio; Bernardo, Esther; Barrera Ramírez, Carlos; Sabaté, Manel; Fernandez, Cristina; Hernández-Antolín, Rosana; Escaned, Javier; Alfonso, Fernando; Macaya, Carlos

2004-04-01

A 300 mg clopidogrel loading-dose (LD) is widely used as an adjunct antithrombotic treatment to reduce the risk of thrombotic events early after coronary stenting (CS). Antithrombotic drugs commonly used during percutaneous coronary interventions, such as heparin and platelet glycoprotein IIb/IIIa inhibitors, but not clopidogrel LD, are weight-adjusted, and few data are available on which is the most effective clopidogrel LD regimen. The aim of this study was to assess whether body mass index (BMI) influenced platelet response to clopidogrel LD in patients undergoing CS. Adenosine diphosphate (ADP)-induced platelet aggregation (PA) was assessed by light transmittance aggregometry in 48 patients on aspirin treatment undergoing CS receiving a 300 mg clopidogrel LD at intervention time. PA was assessed at baseline and up to 24 hours after intervention. Patients were divided into 2 groups according to BMI: overweight (BMI greater than or equal to 25 kg/m2; 29 patients) and normal weight (BMI<25 kg/m2; 19 patients). PA was significantly higher in overweight than in normal weight patients at baseline (60.1+/-18.6%; versus 47.6+/-13.5%; p=0.01), at 24 hours (42.3+/-18.4% versus 38.5+/-18.3%; p=0.02) and during the overall study time (p=0.025). Percentage of inhibition of PA 24 hours following clopidogrel LD was suboptimal (<40%) in 59% and 26% of overweight and normal weight patients, respectively (p=0.04). An elevated BMI was the only independent predictor of suboptimal platelet response. These data suggest that overweight patients may need a higher loading-dose of clopidogrel and/or an adjunct antithrombotic treatment to adequately inhibit platelet aggregation early after CS.

Dose uniformity of loteprednol etabonate ophthalmic gel (0.5%) compared with branded and generic prednisolone acetate ophthalmic suspension (1%).

Science.gov (United States)

Marlowe, Zora T; Davio, Stephen R

2014-01-01

regimen. Dispersion analysis at 120× g showed no drug particle sedimentation for LE ophthalmic gel over the 24-hour testing period, whereas the prednisolone acetate suspensions settled in less than 6 hours. LE ophthalmic gel 0.5% provided consistent dose uniformity at the declared concentration whether or not the bottle was shaken prior to dispensing, whereas Pred Forte® and the generic prednisolone acetate required shaking to provide consistent drug concentrations. LE ophthalmic gel may be beneficial to patients because it eliminates the potential impact on the clinical response of both under- and overdosing.

Amlodipine and valsartan as components of a rational and effective fixed-dose combination

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Bernard Waeber

2009-03-01

Full Text Available Bernard Waeber1, Luis M Ruilope21Division of Clinical Pathophysiology, University Hospital, Faculty of Biology and Medicine, University of Lausanne, Switzerland; 2Hypertension Unit, Hospital 12 de Octubre, Madrid, SpainAbstract: Pharmacological treatment of hypertension is effective in preventing cardiovascular and renal complications. Calcium antagonists and blockers of the renin-angiotensin system are widely used today to initiate antihypertensive therapy but, when given as monotherapy, do not suffice in most patients to normalize blood pressure. Combining the two types of agents considerably increases the antihypertensive efficacy, but not at the expense of a deterioration of tolerability. This is exemplified by the experience accumulated with the recently developed fixed dose combination containing the AT1-receptor blocker valsartan (160 mg and the dihydropyridine amlodipine (5 or 10 mg. In a randomized trial, an 8-week treatment normalized blood pressure (<140/90 mmHg within 8 weeks in a large fraction of hypertensive patients (78.4% and 85.2% using the 5/160 [n = 371] and 10/160 mg [n = 377] dosage, respectively. Like all AT1-receptor blockers valsartan has a placebo-like tolerability. Valsartan prevents to a large extent the occurrence amlodipine-induced peripheral edema. Both amlodipine and valsartan have beneficial effects on cardiovascular morbidity and mortality, as well as protective effects on renal function. The co-administration of these two agents is therefore very attractive, as it enables a rapid and sustained blood pressure control in hypertensive patients. The availability of a fixed-dose combination based on amlodipine and valsartan is expected therefore to facilitate the management of hypertension, to improve long-term adherence with antihypertensive therapy and, ultimately, to have a positive impact on cardiovascular and renal outcomes.Keywords: antihypertensive therapy, fixed-dose combination, calcium antagonists

Observational study to characterise 24-hour COPD symptoms and their relationship with patient-reported outcomes: results from the ASSESS study.

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Miravitlles, Marc; Worth, Heinrich; Soler Cataluña, Juan José; Price, David; De Benedetto, Fernando; Roche, Nicolas; Godtfredsen, Nina Skavlan; van der Molen, Thys; Löfdahl, Claes-Göran; Padullés, Laura; Ribera, Anna

2014-10-21

Few studies have investigated the 24-hour symptom profile in patients with COPD or how symptoms during the 24-hour day are inter-related. This observational study assessed the prevalence, severity and relationship between night-time, early morning and daytime COPD symptoms and explored the relationship between 24-hour symptoms and other patient-reported outcomes. The study enrolled patients with stable COPD in clinical practice. Baseline night-time, early morning and daytime symptoms (symptom questionnaire), severity of airflow obstruction (FEV1), dyspnoea (modified Medical Research Council Dyspnoea Scale), health status (COPD Assessment Test), anxiety and depression levels (Hospital Anxiety and Depression Scale), sleep quality (COPD and Asthma Sleep Impact Scale) and physical activity level (sedentary, moderately active or active) were recorded. The full analysis set included 727 patients: 65.8% male, mean ± standard deviation age 67.2 ± 8.8 years, % predicted FEV1 52.8 ± 20.5%. In each part of the 24-hour day, >60% of patients reported experiencing ≥1 symptom in the week before baseline. Symptoms were more common in the early morning and daytime versus night-time (81.4%, 82.7% and 63.0%, respectively). Symptom severity was comparable for each period assessed. Overall, in the week before baseline, 56.7% of patients had symptoms throughout the whole 24-hour day (3 parts of the day); 79.9% had symptoms in ≥2 parts of the 24-hour day. Symptoms during each part of the day were inter-related, irrespective of disease severity (all p < 0.001). Early morning and daytime symptoms were associated with the severity of airflow obstruction (p < 0.05 for both). Night-time, early morning and daytime symptoms were all associated with worse dyspnoea, health status and sleep quality, and higher anxiety and depression levels (all p < 0.001 versus patients without symptoms in each corresponding period). In each part of the 24-hour day, there was also an association between

Validation of a dietary questionnaire assessed with multiple weighed dietary records or 24-hour recalls

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The authors evaluated the validity of a 152-item semiquantitative food frequency questionnaire (SFFQ) by comparing it with two 7-day dietary records (7DDRs) or up to 4 automated self-administered 24-hour recalls (ASA24s) over a 1-year period in the women's Lifestyle Validation Study (2010-2012), con...

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

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Arman Taheri

2015-01-01

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

Front-Loaded Linezolid Regimens Result in Increased Killing and Suppression of the Accessory Gene Regulator System of Staphylococcus aureus

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Brown, Tanya; Parasrampuria, Ridhi; Brazeau, Daniel A.; Forrest, Alan; Kelchlin, Pamela A.; Holden, Patricia N.; Peloquin, Charles A.; Hanna, Debra; Bulitta, Jurgen B.

2012-01-01

Front loading is a strategy used to optimize the pharmacodynamic profile of an antibiotic through the administration of high doses early in therapy for a short duration. Our aims were to evaluate the impact of front loading of linezolid regimens on bacterial killing and suppression of resistance and on RNAIII, the effector molecule of the accessory gene regulator system (encoded by agr) in methicillin-resistant Staphylococcus aureus (MRSA). Time-killing experiments over 48 h were utilized for linezolid against four strains of MRSA: USA100, USA300, USA400, and ATCC 29213. A hollow-fiber infection model simulated traditional and front-loaded human therapeutic regimens of linezolid versus USA300 at 106 CFU/ml over 240 h. Over 48 h in time-kill experiments, linezolid displayed bacteriostatic activity, with reductions of >1 log10 CFU/ml for all strains. Front-loaded regimens that were administered over 5 days, 1,200 mg every 12 h (q12h) (total, 10 doses) and 2,400 mg q12h (total, 10 doses) followed by 300 mg q12h thereafter, resulted in sustained bactericidal activity, with reductions of the area under the CFU curve of −6.15 and −6.03, respectively, reaching undetectable limits at the 10-day study endpoint. All regimens displayed a reduction in RNAIII relative expression at 24 h and 240 h compared with that of the growth control. Monte Carlo simulations predicted a linezolid are promising and may be of utility in severe MRSA infections, where early aggressive therapy is necessary. PMID:22526313

Study comparing 3 hour and 24 hour post-operative removal of bladder catheter and vaginal pack following vaginal surgery: a randomised controlled trial.

Science.gov (United States)

Rajan, Priya; Soundara Raghavan, S; Sharma, Deepak

2017-09-11

Traditional practice after vaginal hysterectomy was to keep the vaginal pack and urinary catheter for 24 hours post operatively. But there were studies that prolonged cathterisation was associated with urinary infection. So this study was conducted to compare the post operative outcome when the urinary catheter and vaginal pack were removed after 3 hours and after 24 hours after surgery. The study was done in the Department of Obstetrics and Gynecology, in a tertiary teaching institute of South India from September 2008 to March 2010. It was a randomised controlled trial involving 200 women undergoing vaginal surgery, who were randomly assigned to 2 groups - catheter and vaginal pack were removed either in 3 h in study group or were removed in 24 h in control group. The outcome of the study were vaginal bleeding, urinary retention, febrile morbidity, and urinary infection. There was no significant difference between the study and control groups with respect to vaginal bleeding (0 and 1%, p = 1), urinary retention (9 and 4%, p = 0.15), febrile morbidity (7 and 4%, p = 0.35), and urinary infection (26% in each group, p = 1.0). Keeping the urinary catheter and vaginal pack for 24 h following vaginal surgery does not offer any additional benefit against removing them after 3 h.

Impact of Different Normality Thresholds for 24-hour ABPM at the Primary Health Care Level.

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Grezzana, Guilherme Brasil; Moraes, David William; Stein, Airton Tetelbon; Pellanda, Lucia Campos

2017-02-01

Hypertension is an important risk factor for cardiovascular outcomes. Primary health care (PHC) physicians should be prepared to act appropriately in the prevention of cardiovascular risk factors. However, the rates of patients with control of blood pressure (BP) remain low. The impact of the reclassification of high BP by 24-hour ambulatory BP monitoring (ABPM) can lead to different medical decisions in PHC. To evaluate the agreement between the BP measured by a conventional method by PHC physicians and by 24-hour ABPM, considering different BP normal thresholds for the 24-hour ABPM according to the V Brazilian ABPM Guidelines and the European Society of Hypertension Guidelines. A cross-sectional study including 569 hypertensive patients. The BP was initially measured by the PHC physicians and, later, by 24-hour ABPM. The BP measurements were obtained independently between the two methods. The therapeutic targets for the conventional BP followed the guidelines by the Eighth Joint National Committee (JNC 8), the V ABPM Brazilian Guidelines, and the 2013 European Hypertension Guidelines. There was an accuracy of 54.8% (95% confidence interval [95%CI] 0.51 - 0.58%) for the BP measured with the conventional method when compared with the 24-hour ABPM, with a sensitivity of 85% (95%CI 80.8 - 88.6%), specificity of 31.9% (95%CI 28.7 - 34.7%), and kappa value of 0.155, when considering the European Hypertension Guidelines. When using more stringent thresholds to characterize the BP as "normal" by ABPM, the accuracy was 45% (95%CI 0.41 - 0.47%) for conventional measurement when compared with 24-hour ABPM, with a sensitivity of 86.7% (95%CI 0.81 - 0.91%), specificity of 29% (95%CI 0.26 - 0.30%), and kappa value of 0.103. The BP measurements obtained by PHC physicians showed low accuracy when compared with those obtained by 24-hour ABPM, regardless of the threshold set by the different guidelines. A hipertensão arterial sistêmica é um fator de risco importante para

Safety and adherence to intermittent pre-exposure prophylaxis (PrEP for HIV-1 in African men who have sex with men and female sex workers.

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Gaudensia Mutua

Full Text Available Little is known about safety of and adherence to intermittent HIV PrEP regimens, which may be more feasible than daily dosing in some settings. We present safety and adherence data from the first trial of an intermittent PrEP regimen among Kenyan men who have sex with men (MSM and female sex workers (FSW.MSM and FSW were randomized to daily oral FTC/TDF or placebo, or intermittent (Monday, Friday and within 2 hours after sex, not to exceed one dose per day oral FTC/TDF or placebo in a 2:1:2:1 ratio; volunteers were followed monthly for 4 months. Adherence was assessed with the medication event monitoring system (MEMS. Sexual activity data were collected via daily text message (SMS queries and timeline followback interviews with a one-month recall period. Sixty-seven men and 5 women were randomized into the study. Safety was similar among all groups. Median MEMS adherence rates were 83% [IQR: 63-92] for daily dosing and 55% [IQR:28-78] for fixed intermittent dosing (p = 0.003, while adherence to any post-coital doses was 26% [IQR:14-50]. SMS response rates were low, which may have impaired measurement of post-coital dosing adherence. Acceptability of PrEP was high, regardless of dosing regimen.Adherence to intermittent dosing regimens, fixed doses, and in particular coitally-dependent doses, may be more difficult than adherence to daily dosing. However, intermittent dosing may still be appropriate for PrEP if intracellular drug levels, which correlate with prevention of HIV acquisition, can be attained with less than daily dosing and if barriers to adherence can be addressed. Additional drug level data, qualitative data on adherence barriers, and better methods to measure sexual activity are necessary to determine whether adherence to post-coital PrEP could be comparable to more standard regimens.ClinicalTrials.gov NCT00971230.

Raman spectroscopic assessment of degree of conversion of bulk-fill resin composites--changes at 24 hours post cure.

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Par, M; Gamulin, O; Marovic, D; Klaric, E; Tarle, Z

2015-01-01

The aim of this study was to determine degree of conversion (DC) of solid and flowable bulk-fill composites immediately and after 24 hours and investigate the variations of DC at surface and depths up to 4 mm. Eight bulk-fill composites (Tetric EvoCeram Bulk Fill [shades IVA and IVB], Quixfil, X-tra fil, Venus Bulk Fill, X-tra Base, SDR, Filtek Bulk Fill) were investigated, and two conventional composites (GrandioSO, X-Flow) were used as controls. The samples (n = 5) were cured for 20 seconds with irradiance of 1090 mW/cm(2). Raman spectroscopic measurements were made immediately after curing on sample surfaces and after 24 hours of dark storage at surface and at incremental depths up to 4 mm. Mean DC values were compared using repeated measures analysis of variance (ANOVA) and t-test for dependent samples. Surface DC values immediately after curing ranged from 59.1%-71.8%, while the 24-hour postcure values ranged from 71.3%-86.1%. A significant increase of DC was observed 24 hours post cure for all bulk-fill composites, which amounted from 11.3% to 16.9%. Decrease of DC through depths up to 4 mm varied widely among bulk-fill composites and ranged from 2.9% to 19.7%. All bulk-fill composites presented a considerable 24-hour postcure DC increase and clinically acceptable DC at depths up to 4 mm. Conventional control composites were sufficiently cured only up to 2 mm, despite significant postcure polymerization.

Serum magnesium levels in patients with pre-eclampsia and eclampsia with different regimens of magnesium sulphate

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Arpita Singh

2013-01-01

Full Text Available Background Pre-eclampsia and the subsequent eclampsia account for a common cause of maternal mortality worldwide and efforts aimed at reducing its menace are vital. Objective To estimate the serum magnesium levels in pre-eclampsia and eclampsia and to study the effect of using different regimens of magnesium sulphate. Methods 70 cases of pre-eclampsia and eclampsia and 35 normal pregnant women as controls were studied. Serum magnesium levels were estimated using Atomic Absorption Spectrophotometer (Model AAS-4139 at baseline and at frequent intervals during gestation and the overall parameters were meticulously observed. Results Majority(60%ofstudiedcaseswasnulliparawithgestationageof36-40 weeks. Statistically significant reduction of mean diastolic blood pressure and protein-urea was observed after using both intramuscular and intravenous regimens of magnesium sulphate. Mean initial serum magnesium level (mg/dl±SD was 1.81±0.58 in group A,1.55±0.41 in group B and 1.49±0.41 in group C. Mean serum magnesium levels during first 4 hours after therapy were statistically significant between intramuscular and intravenous regimen groups while same were statistically insignificant at 8,12,16,24 and 32 hours. Besides, few minor side effects including headache, vomiting, reduced tendon reflexes and thrombocytopenia, no severe side effects and no maternal mortality were seen. Conclusion Hypomagnesemia occurs during states of preeclampsia and eclampsia, and, administration of magnesium sulphate is effective and safe in preventing maternal mortality.

Serum magnesium levels in patients with pre-eclampsia and eclampsia with different regimens of magnesium sulphate

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Arpita Singh

2013-03-01

Full Text Available Background Pre-eclampsia and the subsequent eclampsia account for a common cause of maternal mortality worldwide and efforts aimed at reducing its menace are vital. Objective To estimate the serum magnesium levels in pre-eclampsia and eclampsia and to study the effect of using different regimens of magnesium sulphate. Methods 70 cases of pre-eclampsia and eclampsia and 35 normal pregnant women as controls were studied. Serum magnesium levels were estimated using Atomic Absorption Spectrophotometer (Model AAS-4139 at baseline and at frequent intervals during gestation and the overall parameters were meticulously observed. Results Majority (60% of studied cases was nullipara with gestation age of 36-40 weeks. Statistically significant reduction of mean diastolic blood pressure and protein-urea was observed after using both intramuscular and intravenous regimens of magnesium sulphate. Mean initial serum magnesium level (mg/dl±SD was 1.81±0.58 in group A,1.55±0.41 in group B and 1.49±0.41 in group C. Mean serum magnesium levels during first 4 hours after therapy were statistically significant between intramuscular and intravenous regimen groups while same were statistically insignificant at 8,12,16,24 and 32 hours. Besides, few minor side effects including headache, vomiting, reduced tendon reflexes and thrombocytopenia, no severe side effects and no maternal mortality were seen. Conclusion Hypomagnesemia occurs during states of preeclampsia and eclampsia, and, administration of magnesium sulphate is effective and safe in preventing maternal mortality.

Tasimelteon (Hetlioz™): A New Melatonin Receptor Agonist for the Treatment of Non-24-Hour Sleep-Wake Disorder.

Science.gov (United States)

Bonacci, Janene M; Venci, Jineane V; Gandhi, Mona A

2015-10-01

In January 2014, the US Food and Drug Administration approved tasimelteon (Hetlioz™), a melatonin-receptor agonist for the treatment of non-24-hour sleep-wake disorder. This article provides an overview of the mechanism of action, pharmacokinetic properties, as well as the clinical efficacy, safety, and tolerability of tasimelteon. Relevant information was identified through a comprehensive literature search of several databases using the key words tasimelteon, Non-24-hour Sleep-Wake disorder, Non-24, and melatonin. Further information was obtained from the tasimelteon package insert, fda.gov, clinicaltrials.gov, briefing materials provided by Vanda Pharmaceuticals, and posters from scientific meetings. © The Author(s) 2014.

Results of a Prospective Study of High-Dose or Conventional Anthracycline-Cyclophosphamide Regimen Plus Radiotherapy for Localized Adult Non-Hodgkin’s Primary Bone Lymphoma

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A. Schmidt-Tanguy

2014-01-01

Full Text Available Background. Primary bone lymphoma (PBL is a rare entity that has only been reviewed in one prospective and small retrospective studies, from which it is difficult to establish treatment guidelines. We prospectively evaluated high-dose or conventional anthracycline-cyclophosphamide dose and radiotherapy for PBL. Patients and Methods. The GOELAMS prospective multicenter study (1986–1998 enrolled adults with localized high-grade PBL according to age and performance status (PS. Patients <60 years received a high-dose CHOP regimen (VCAP and those ≥60 years a conventional anthracycline-cyclophosphamide regimen (VCEP-bleomycin; all received intrathecal chemotherapy and local radiotherapy. Results. Among the 26 patients included (VCAP: 19; VCEP-bleomycin: 7, 39% had poor PS ≥2. With a median follow-up of 8 years, overall survival, event-free survival, and relapse-free survival were 64%, 62%, and 65%, respectively, with no significant difference between treatment groups. Poor PS was significantly associated with shorter OS and EFS. Conclusions. Our results confirm the efficacy of our age-based therapeutic strategy. High-doses anthracycline-cyclophosphamide did not improve the outcome. VCEP-bleomycin is effective and well tolerated for old patients. The intensification must be considered for patients with PS ≥2, a poor prognostic factor.

Comparing Serum and 24-hour Urine Calcium between Preeclamptic and Non-preeclamptic Patients

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N Shahbazian

2014-02-01

Results: No statistically significant difference was found between serum calcium means in the two groups (p=0.07, though mean of 24-hour urine calcium in preeclamptic patients was significantly lower than that of control group (p=0.0003. In preeclamptic group, the degree of hypocalciuria was related to disordered liver enzymes, serum creatinine greater than 1.2 mg/dl, thrombocytopenia and proteinuria more than 2g/24h. Conclusion: Preeclampsia is associated with hypocalciuria; the more hypocalciuria there exists , the more preeclampsia is observed.

Short communication Responses of Abyssinian Jennies to ...

African Journals Online (AJOL)

effects (locomotor disturbances, respiratory distress, tachycardia and sweat- ing) at doses lower than 100 mg but the effects are profound at doses of 400 mg and above (Pharmacia and Upjohn Company, 2004). No side effect was re- corded in a regimen of 0.5 mg PGF2 given24 hours apart compared to a 10 mg.

Efficacy of split hours part-time patching versus continuous hours part-time patching for treatment of anisometropic amblyopia in children: a pilot study.

Science.gov (United States)

Sachdeva, Virender; Mittal, Vaibhev; Kekunnaya, Ramesh; Gupta, Amit; Rao, Harsha L; Mollah, Joseph; Sontha, Anand; Gunturu, Rekha; Rao, B Venkateshwar

2013-07-01

To compare efficacy of 'split hours part-time patching' and 'continuous hours part-time patching' for the treatment of anisometropic amblyopia. We designed a prospective, interventional, non-randomised, comparative pilot study involving children between 4 and 11 years of age with anisometropic amblyopia who were treated with either continuous wear (Group A) or split hours part-time patching (Group B) as per parents wish, after appropriate discussion with the parents. Children were followed-up for the improvement in visual acuity and the compliance at each follow-up visit. 44 and 24 children were recruited in Group A and Group B, respectively (mean ± SD baseline BCVA of the amblyopic eye: 0.99 ± 0.32 and 0.95 ± 0.23 logMAR, respectively). BCVA (adjusted for baseline BCVA and age) at 3 months in Group A (0.59 ± 0.24) was comparable (p=0.08) with that in Group B (0.71 ± 0.24). This was same even at 6 months (0.51 ± 0.25 in Group A and 0.59 ± 0.25 in Group B, p=0.25). The improvement in BCVA at 3 months was also comparable (p=0.06) in Group A (0.39 ± 0.23) and Group B (0.26 ± 0.23). The improvement in BCVA at 6 months was also comparable (p=0.14) in Group A (0.47 ± 0.26) and Group B (0.37 ± 0.26). Both patching regimens lead to significant and comparable improvement in BCVA in anisometropic amblyopia up to 6 months of follow-up.

Assessment of dietary sodium intake using a food frequency questionnaire and 24-hour urinary sodium excretion: a systematic literature review.

Science.gov (United States)

McLean, Rachael M; Farmer, Victoria L; Nettleton, Alice; Cameron, Claire M; Cook, Nancy R; Campbell, Norman R C

2017-12-01

Food frequency questionnaires (FFQs) are often used to assess dietary sodium intake, although 24-hour urinary excretion is the most accurate measure of intake. The authors conducted a systematic review to investigate whether FFQs are a reliable and valid way of measuring usual dietary sodium intake. Results from 18 studies are described in this review, including 16 validation studies. The methods of study design and analysis varied widely with respect to FFQ instrument, number of 24-hour urine collections collected per participant, methods used to assess completeness of urine collections, and statistical analysis. Overall, there was poor agreement between estimates from FFQ and 24-hour urine. The authors suggest a framework for validation and reporting based on a consensus statement (2004), and recommend that all FFQs used to estimate dietary sodium intake undergo validation against multiple 24-hour urine collections. ©2017 Wiley Periodicals, Inc.

Phase I dose-finding study of cabazitaxel administered weekly in patients with advanced solid tumours

International Nuclear Information System (INIS)

Fumoleau, Pierre; Trigo, Jose Manuel; Isambert, Nicolas; Sémiond, Dorothée; Gupta, Sunil; Campone, Mario

2013-01-01

Cabazitaxel is approved in patients with metastatic hormone-refractory prostate cancer previously treated with a docetaxel-containing regimen. This study evaluated a weekly cabazitaxel dosing regimen. Primary objectives were to report dose-limiting toxicities (DLTs) and to determine the maximum tolerated dose (MTD). Efficacy, safety and pharmacokinetics were secondary objectives. Cabazitaxel was administered weekly (1-hour intravenous infusion at 1.5–12 mg/m2 doses) for the first 4 weeks of a 5-week cycle in patients with solid tumours. Monitoring of DLTs was used to determine the MTD and the recommended weekly dose. Thirty-one patients were enrolled. Two of six patients experienced DLTs at 12 mg/m 2 , which was declared the MTD. Gastrointestinal disorders were the most common adverse event. Eight patients developed neutropenia (three ≥ Grade 3); one occurrence of febrile neutropenia was reported. There were two partial responses (in breast cancer) and 13 patients had stable disease (median duration of 3.3 months). Increases in C max and AUC 0–t were dose proportional for the 6–12 mg/m 2 doses. The MTD of weekly cabazitaxel was 12 mg/m 2 and the recommended weekly dose was 10 mg/m 2 . The observed safety profile and antitumour activity of cabazitaxel were consistent with those observed with other taxanes in similar dosing regimens. The study was registered with ClinicalTrials.gov as http://www.clinicaltrials.gov/ct2/show/NCT01755390

A Phase I/II Trial of Intensity Modulated Radiation (IMRT) Dose Escalation With Concurrent Fixed-dose Rate Gemcitabine (FDR-G) in Patients With Unresectable Pancreatic Cancer

International Nuclear Information System (INIS)

Ben-Josef, Edgar; Schipper, Mathew; Francis, Isaac R.; Hadley, Scott; Ten-Haken, Randall; Lawrence, Theodore; Normolle, Daniel; Simeone, Diane M.; Sonnenday, Christopher; Abrams, Ross; Leslie, William; Khan, Gazala; Zalupski, Mark M.

2012-01-01

Purpose: Local failure in unresectable pancreatic cancer may contribute to death. We hypothesized that intensification of local therapy would improve local control and survival. The objectives were to determine the maximum tolerated radiation dose delivered by intensity modulated radiation with fixed-dose rate gemcitabine (FDR-G), freedom from local progression (FFLP), and overall survival (OS). Methods and Materials: Eligibility included pathologic confirmation of adenocarcinoma, radiographically unresectable, performance status of 0-2, absolute neutrophil count of ≥1500/mm 3 , platelets ≥100,000/mm 3 , creatinine 2 /100 min intravenously) was given on days −22 and −15, 1, 8, 22, and 29. Intensity modulated radiation started on day 1. Dose levels were escalated from 50-60 Gy in 25 fractions. Dose-limiting toxicity was defined as gastrointestinal toxicity grade (G) ≥3, neutropenic fever, or deterioration in performance status to ≥3 between day 1 and 126. Dose level was assigned using TITE-CRM (Time-to-Event Continual Reassessment Method) with the target dose-limiting toxicity (DLT) rate set to 0.25. Results: Fifty patients were accrued. DLTs were observed in 11 patients: G3/4 anorexia, nausea, vomiting, and/or dehydration (7); duodenal bleed (3); duodenal perforation (1). The recommended dose is 55 Gy, producing a probability of DLT of 0.24. The 2-year FFLP is 59% (95% confidence interval [CI]: 32-79). Median and 2-year overall survival are 14.8 months (95% CI: 12.6-22.2) and 30% (95% CI 17-45). Twelve patients underwent resection (10 R0, 2 R1) and survived a median of 32 months. Conclusions: High-dose radiation therapy with concurrent FDR-G can be delivered safely. The encouraging efficacy data suggest that outcome may be improved in unresectable patients through intensification of local therapy.

Dose uniformity of loteprednol etabonate ophthalmic gel (0.5% compared with branded and generic prednisolone acetate ophthalmic suspension (1%

Directory of Open Access Journals (Sweden)

Marlowe ZT

2013-12-01

below the declared concentration for drops expressed at the beginning of the 2-week dosing regimen and significantly above the declared concentration for drops expressed near the end of the dosing regimen. Dispersion analysis at 120× g showed no drug particle sedimentation for LE ophthalmic gel over the 24-hour testing period, whereas the prednisolone acetate suspensions settled in less than 6 hours.Conclusion: LE ophthalmic gel 0.5% provided consistent dose uniformity at the declared concentration whether or not the bottle was shaken prior to dispensing, whereas Pred Forte® and the generic prednisolone acetate required shaking to provide consistent drug concentrations. LE ophthalmic gel may be beneficial to patients because it eliminates the potential impact on the clinical response of both under- and overdosing.Keywords: dose uniformity, Lotemax, Pred Forte, nonsettling, ophthalmic formulation, simulated dosing

The dependence of the magnitude of induced adaptive responseon on the dose of pre-irradiation of cultured human lymphocytes under the optimum irradiation time scheme

International Nuclear Information System (INIS)

Mortazavi, S.M.J.; Mozdarani, H.

2000-01-01

Human lymphocytes exposed to low doses of X-rays, become less susceptible to the induction of chromosome aberrations by subsequent exposure to high doses of X-rays. This has been termed the radioadaptive response. One of the most important questions in the adaptive response studies was that of the possible existence of an optimum adapting dose. Early experiments indicated that this response could be induced by low doses of X-rays from 1 cGy to 20 cGy. Recently, it has been interestingly shown that the time scheme of exposure to adapting and challenge doses plays an important role in determination of the magnitude of the induced adaptive response. In this study, using the optimum irradiation time scheme (24-48), we have monitored the cytogenetic endpoint of chromosome aberrations to assess the magnitude of adaptation to ionizing radiation in the cultured human lymphocytes. Lymphocytes were pre-exposed to an adapting dose of 1-20 cGy at 24 hours, before an acute challenge dose of 1 or 2 Gy at 48 hours. Cells were fixed at 54 hours. Lymphocytes, which were pretreated with 5 as well as 10 cGy adapting doses, had significantly fewer chromosome aberrations. In spite of the fact that lymphocytes of some of our blood donors which were pre-treated with 1 or 20 cGy adapting doses, showed an adaptive response, the pooled data (all donors) indicated that such an induction of adaptive response can not be observed in these lymphocytes. The overall pattern of the induced adaptive response, indicated that in human lymphocyte (at least under the above mentioned irradiation scheme), 5 cGy and 10 cGy adapting doses are the optimum doses. (author)

Fracture during intravenous bisphosphonate treatment in a child with osteogenesis imperfecta: an argument for a more frequent, low-dose treatment regimen.

Science.gov (United States)

Biggin, Andrew; Briody, Julie N; Ormshaw, Elizabeth; Wong, Karen K Y; Bennetts, Bruce H; Munns, Craig F

2014-01-01

Intravenous bisphosphonate therapy is the mainstay of medical treatment in osteogenesis imperfecta (OI) and has been shown to increase bone mass, decrease bone pain, improve mobility, and reduce the incidence of fractures. Sclerotic metaphyseal lines parallel to the growth plate are seen on long bone radiographs following cyclical intravenous therapy. These areas create stress risers within the bone that may act as foci for subsequent fractures as exemplified in this clinical case. An 8-year-old girl with OI sustained a distal radial fracture following 3 years of treatment with 6-monthly intravenous zoledronate. Her diagnosis, response to treatment, and subsequent fracture at a sclerotic metaphyseal line is described. Peripheral quantitative computer tomography was used to characterise the presence of multiple stress risers at the distal forearm. Trabecular bone mineral density fluctuated from 34 to 126% compared to neighbouring 2-mm regions. There remain many unanswered questions about optimal bisphosphonate treatment regimens in children with OI. The formation of stress risers following intravenous bisphosphonate treatment raises the hypothesis that a more frequent and low-dose bisphosphonate regimen would provide more uniform dosing of bone in the growing child and reduce the likelihood of fractures compared to current treatment practices.

Observational study to characterise 24-hour COPD symptoms and their relationship with patient-reported outcomes : results from the ASSESS study

NARCIS (Netherlands)

Miravitlles, Marc; Worth, Heinrich; Soler Cataluna, Juan Jose; Price, David; De Benedetto, Fernando; Roche, Nicolas; Godtfredsen, Nina Skavlan; van der Molen, Thys; Lofdahl, Claes-Goran; Padulles, Laura; Ribera, Anna

2014-01-01

Background: Few studies have investigated the 24-hour symptom profile in patients with COPD or how symptoms during the 24-hour day are inter-related. This observational study assessed the prevalence, severity and relationship between night-time, early morning and daytime COPD symptoms and explored

24 Hours of Sleep, Sedentary Behavior, and Physical Activity with Nine Wearable Devices

OpenAIRE

Rosenberger, Mary E.; Buman, Matthew P.; Haskell, William L.; McConnell, Michael V.; Carstensen, Laura L.

2016-01-01

Getting enough sleep, exercising and limiting sedentary activities can greatly contribute to disease prevention and overall health and longevity. Measuring the full 24-hour activity cycle - sleep, sedentary behavior (SED), light intensity physical activity (LPA) and moderate-to-vigorous physical activity (MVPA) - may now be feasible using small wearable devices.

Dose escalation by image-guided intensity-modulated radiotherapy leads to an increase in pain relief for spinal metastases: a comparison study with a regimen of 30 Gy in 10 fractions.

Science.gov (United States)

He, Jinlan; Xiao, Jianghong; Peng, Xingchen; Duan, Baofeng; Li, Yan; Ai, Ping; Yao, Min; Chen, Nianyong

2017-12-22

Under the existing condition that the optimum radiotherapy regimen for spinal metastases is controversial, this study investigates the benefits of dose escalation by image-guided intensity-modulated radiotherapy (IG-IMRT) with 60-66 Gy in 20-30 fractions for spinal metastases. In the dose-escalation group, each D50 of planning gross tumor volume (PGTV) was above 60 Gy and each Dmax of spinal cord planning organ at risk volume (PRV) was below 48 Gy. The median biological effective dose (BED) of Dmax of spinal cord was lower in the dose-escalation group compared with that in the 30-Gy group (69.70 Gy vs. 83.16 Gy, p pain responses were better in the dose-escalation group than those in the 30-Gy group ( p = 0.005 and p = 0.024), and the complete pain relief rates were respectively 73.69% and 34.29% ( p = 0.006), 73.69% and 41.38% ( p = 0.028) in two compared groups. In the dose-escalation group, there is a trend of a longer duration of pain relief, a longer overall survival and a lower incidence of acute radiation toxicities. No late radiation toxicities were observed in both groups. Dosimetric parameters and clinical outcomes, including pain response, duration of pain relief, radiation toxicities and overall survival, were compared among twenty-five metastatic spinal lesions irradiated with the dose-escalation regimen and among forty-four lesions treated with the 30-Gy regimen. Conventionally-fractionated IG-IMRT for spinal metastases could escalate dose to the vertebral lesions while sparing the spinal cord, achieving a better pain relief without increasing radiation complications.

Evaluation of the Efficacy and Safety of High Dose Short Duration Enrofloxacin Treatment Regimen for Uncomplicated Urinary Tract Infections in Dogs

Science.gov (United States)

Westropp, JL; Sykes, JE; Irom, S; Daniels, JB; Smith, A; Keil, D; Settje, T; Wang, Y; Chew, DJ

2012-01-01

Background Uncomplicated urinary tract infections (UTI) in dogs usually are treated with antimicrobial drugs for 10–14 days. Shorter duration antimicrobial regimens have been evaluated in human patients. Hypothesis A high dose short duration (HDSD) enrofloxacin protocol administered to dogs with uncomplicated UTI will not be inferior to a 14-day treatment regimen with amoxicillin-clavulanic acid. Animals Client-owned adult, otherwise healthy dogs with aerobic bacterial urine culture yielding ≥103 CFU/mL of bacteria after cystocentesis. Methods Prospective, multicenter, controlled, randomized blinded clinical trial. Enrolled dogs were randomized to group 1 (enrofloxacin 18–20 mg/kg PO q24h for 3 days) or group 2 (amoxicillin-clavulanic acid 13.75–25 mg/kg PO q12h for 14 days). Urine cultures were obtained at days 0, 10, and 21. Microbiologic and clinical cure rates were evaluated 7 days after antimicrobial treatment was discontinued. Lower urinary tract signs and adverse events also were recorded. Results There were 35 dogs in group 1 and 33 in group 2. The microbiologic cure rate was 77.1 and 81.2% for groups 1 and 2, respectively. The clinical cure rate was 88.6 and 87.9% for groups 1 and 2, respectively. Cure rates between groups did not differ according to the selected margin of noninferiority. Conclusions and Clinical Importance HDSD enrofloxacin treatment was not inferior to a conventional amoxicillin-clavulanic acid protocol for the treatment of uncomplicated bacterial UTI in dogs. Further research is warranted to determine if this protocol will positively impact owner compliance and decrease the emergence of antimicrobial resistance. PMID:22486931

Disposition of 2,4-dichlorophenoxyacetic acid dimethylamine by Fischer 344 rats dosed orally and dermally

International Nuclear Information System (INIS)

Pelletier, O.; Ritter, L.; Caron, J.; Somers, D.

1989-01-01

The dimethylamine salt of 14C-ring-labeled 2,4-D was administered to Fischer 344 rats orally (1 and 0.4 mg/kg body weight) and dermally (10 mg/kg body weight). Absorption, distribution, and elimination were determined from 14C-labeled 2,4-D in blood, tissues, and excreta. Quantitatively, most of the orally administered dose (94-96%) became systemically available within 6 h. Following dermal administration 10% of the dose became systemically available over 72 h. However, peak concentrations in blood and kidneys were achieved within 30 min of dosing by either route. By 1.5 h after dosing, 2,4-D concentrations in blood, muscle, liver, and kidneys had decreased in both the orally dosed and dermally dosed animals. Between 2 and 8 h, the blood, muscle, liver and kidney concentrations in dermally dosed animals maintained a plateau while urinary excretion increased, presumably due to continued absorption of 2,4-D from the skin. The concentrations in orally dosed animals continued to decrease. Following 7 h of dermal exposure, skin cleansing removed about 63% of the applied dose; about 17% of the applied dose remained at the site of dermal dosing. At 8 h, 2,4-D concentrations in blood, muscle, liver, and kidneys of dermally dosed animals began to decrease, most likely a result of the removal of the reservoir on the skin. However, 2,4-D continued to be absorbed from skin site, resulting in a slower decline of the 2,4-D concentrations in these tissues over remainder of the 72-h study period. By comparison, in animals that had been orally dosed, the absorbed dose was almost completely excreted within 24 h

The Impact of a One-Dose versus Two-Dose Oral Cholera Vaccine Regimen in Outbreak Settings: A Modeling Study

Science.gov (United States)

Azman, Andrew S.; Luquero, Francisco J.; Ciglenecki, Iza; Grais, Rebecca F.; Sack, David A.; Lessler, Justin

2015-01-01

Background In 2013, a stockpile of oral cholera vaccine (OCV) was created for use in outbreak response, but vaccine availability remains severely limited. Innovative strategies are needed to maximize the health impact and minimize the logistical barriers to using available vaccine. Here we ask under what conditions the use of one dose rather than the internationally licensed two-dose protocol may do both. Methods and Findings Using mathematical models we determined the minimum relative single-dose efficacy (MRSE) at which single-dose reactive campaigns are expected to be as or more effective than two-dose campaigns with the same amount of vaccine. Average one- and two-dose OCV effectiveness was estimated from published literature and compared to the MRSE. Results were applied to recent outbreaks in Haiti, Zimbabwe, and Guinea using stochastic simulations to illustrate the potential impact of one- and two-dose campaigns. At the start of an epidemic, a single dose must be 35%–56% as efficacious as two doses to avert the same number of cases with a fixed amount of vaccine (i.e., MRSE between 35% and 56%). This threshold decreases as vaccination is delayed. Short-term OCV effectiveness is estimated to be 77% (95% CI 57%–88%) for two doses and 44% (95% CI −27% to 76%) for one dose. This results in a one-dose relative efficacy estimate of 57% (interquartile range 13%–88%), which is above conservative MRSE estimates. Using our best estimates of one- and two-dose efficacy, we projected that a single-dose reactive campaign could have prevented 70,584 (95% prediction interval [PI] 55,943–86,205) cases in Zimbabwe, 78,317 (95% PI 57,435–100,150) in Port-au-Prince, Haiti, and 2,826 (95% PI 2,490–3,170) cases in Conakry, Guinea: 1.1 to 1.2 times as many as a two-dose campaign. While extensive sensitivity analyses were performed, our projections of cases averted in past epidemics are based on severely limited single-dose efficacy data and may not fully capture

The Impact of a One-Dose versus Two-Dose Oral Cholera Vaccine Regimen in Outbreak Settings: A Modeling Study.

Directory of Open Access Journals (Sweden)

Andrew S Azman

2015-08-01

Full Text Available In 2013, a stockpile of oral cholera vaccine (OCV was created for use in outbreak response, but vaccine availability remains severely limited. Innovative strategies are needed to maximize the health impact and minimize the logistical barriers to using available vaccine. Here we ask under what conditions the use of one dose rather than the internationally licensed two-dose protocol may do both.Using mathematical models we determined the minimum relative single-dose efficacy (MRSE at which single-dose reactive campaigns are expected to be as or more effective than two-dose campaigns with the same amount of vaccine. Average one- and two-dose OCV effectiveness was estimated from published literature and compared to the MRSE. Results were applied to recent outbreaks in Haiti, Zimbabwe, and Guinea using stochastic simulations to illustrate the potential impact of one- and two-dose campaigns. At the start of an epidemic, a single dose must be 35%-56% as efficacious as two doses to avert the same number of cases with a fixed amount of vaccine (i.e., MRSE between 35% and 56%. This threshold decreases as vaccination is delayed. Short-term OCV effectiveness is estimated to be 77% (95% CI 57%-88% for two doses and 44% (95% CI -27% to 76% for one dose. This results in a one-dose relative efficacy estimate of 57% (interquartile range 13%-88%, which is above conservative MRSE estimates. Using our best estimates of one- and two-dose efficacy, we projected that a single-dose reactive campaign could have prevented 70,584 (95% prediction interval [PI] 55,943-86,205 cases in Zimbabwe, 78,317 (95% PI 57,435-100,150 in Port-au-Prince, Haiti, and 2,826 (95% PI 2,490-3,170 cases in Conakry, Guinea: 1.1 to 1.2 times as many as a two-dose campaign. While extensive sensitivity analyses were performed, our projections of cases averted in past epidemics are based on severely limited single-dose efficacy data and may not fully capture uncertainty due to imperfect

Low-dose hydrocortisone (HC) replacement therapy is associated with improved bone remodeling balance in hypopituitary subjects

LENUS (Irish Health Repository)

Behan, L A

2011-06-01

The effect of commonly used glucocorticoid replacement regimens on bone health in hypopituitary subjects is not well known. We aimed to assess the effect of 3 hydrocortisone (HC) replacement dose regimens on bone turnover in this group.10 hypopituitary men with severe ACTH deficiency were randomised in a crossover design to 3 HC dose regimens, Dose A (20mg mane, 10mg tarde), Dose B (10mg twice daily) and Dose C (10mg mane, 5mg tarde). Following 6 weeks of each regimen participants underwent fasting sampling of bone turnover markers.Data from matched controls were used to produce a Z score for subject bone formation and resorption markers and to calculate the bone remodeling balance (formation Z score-resorption Z score) and turnover index ((formation Z + resorption Z)\\/2). A positive bone remodeling balance with increased turnover is consistent with a favourable bone cycle. Data are expressed as median (range).The Pro Collagen Type 1 Peptide (PINP) bone formation Z-score was significantly increased in Dose C, (1.805 (-0.6-10.24)) compared to Dose A (0.035 (-1.0-8.1)) p<0.05 while there was no difference in the C-terminal crosslinking telopeptide (CTx) resorption Z score. The bone remodeling balance was significantly lower for dose A -0.02 (-1.05-4.12) compared to dose C 1.13 (0.13-6.4) (p<0.05). Although there was a trend to an increased bone turnover index with the lower dose regimen, this was not statistically significant.Low dose HC replacement (10mg mane\\/5 mg tarde) was associated with increased bone formation and improved bone remodeling balance which is associated with a more favourable bone cycle. This may have a long term beneficial effect on bone health.

Clinical utility of fixed-dose combinations in hypertension: evidence for the potential of nebivolol/valsartan

Directory of Open Access Journals (Sweden)

Varagic J

2014-11-01

Full Text Available Jasmina Varagic,1–3 Henry Punzi,4,5 Carlos M Ferrario2,3,61Hypertension and Vascular Research Center, 2Division of Surgical Sciences, 3Department of Physiology and Pharmacology, Wake Forest University, Winston-Salem, NC USA; 4Trinity Hypertension and Diagnostic Research Center, Carrollton, TX, USA; 5Department of Family and Community Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA; 6Department of Internal Medicine and Nephrology, Wake Forest University, Winston-Salem, NC, USAAbstract: Despite significant advances in pharmacologic approaches to treat hypertension during the last decades, hypertension- and hypertension-related organ damage are still a high health and economic burden because a large proportion of patients with hypertension do not achieve optimal blood pressure control. There is now general agreement that combination therapy with two or more antihypertensive drugs is required for targeted blood pressure accomplishment and reduction of global cardiovascular risk. The goals of combination therapies are to reduce long-term cardiovascular events by targeting different mechanism underlying hypertension and target organ disease, to block the counterregulatory pathways activated by monotherapies, to improve tolerability and decrease the adverse effects of up-titrated single agents, and to increase persistence and adherence with antihypertensive therapy. Multiple clinical trials provide evidence that fixed-dose combinations in a single pill offer several advantages when compared with loose-dose combinations. This review discusses the advances in hypertension control and associated cardiovascular disease as they relate to the prospect of combination therapy targeting a third-generation beta (β 1-adrenergic receptor (nebivolol and an angiotensin II receptor blocker (valsartan in fixed-dose single-pill formulations.Keywords: blood pressure control, hypertension, β1-adrenergic receptor, renin angiotensin system

Comparison of Thromboemboli Prophylactic Effect of Aspirin and Low Dose Warfarin in Standard Risk Multiple Myeloma Patients that Treated with Regimens Containing Thalidomide

Directory of Open Access Journals (Sweden)

Seyed Amir Dadkhahi

2017-05-01

Full Text Available Abstract Background: Most of the current regimens in the treatment of multiple myeloma include thalidomide. Thalidomide is a modulator of the immune system and according to several studies, its main complication is thromboembolism. The aim of this study is to compare the thromboemboli prophylactic effect of aspirin and low dose warfarin in standard risk multiple myeloma patients that treated with regimens containing thalidomide. Materials and Methods: In this double- blind clinical trial study, sixty-six patients with multiple myeloma under treatment with thalidomide-containing regimens with standard risk for thromboembolism who were admitted to Khansari hospital, entered the study according to inclusion and exclusion criteria. The incidence of thromboembolism in these patients was evaluated. Results: Five patients in the warfarin group and 2 patients in the aspirin group had thromboemboli. Chi square analyses showed no significant difference between groups (p=0.635. Conclusion: The results showed that both drugs are effective in preventing thromboembolism and can be used as a prophylactic treatment.

Dose-Response Analysis of RNA-Seq Profiles in Archival Formalin-Fixed Paraffin-Embedded (FFPE) Samples.

Science.gov (United States)

Use of archival resources has been limited to date by inconsistent methods for genomic profiling of degraded RNA from formalin-fixed paraffin-embedded (FFPE) samples. RNA-sequencing offers a promising way to address this problem. Here we evaluated transcriptomic dose responses us...

Single low-dose primaquine for blocking transmission of Plasmodium falciparum malaria - a proposed model-derived age-based regimen for sub-Saharan Africa.

Science.gov (United States)

Taylor, W Robert; Naw, Htee Khu; Maitland, Kathryn; Williams, Thomas N; Kapulu, Melissa; D'Alessandro, Umberto; Berkley, James A; Bejon, Philip; Okebe, Joseph; Achan, Jane; Amambua, Alfred Ngwa; Affara, Muna; Nwakanma, Davis; van Geertruyden, Jean-Pierre; Mavoko, Muhindo; Lutumba, Pascal; Matangila, Junior; Brasseur, Philipe; Piola, Patrice; Randremanana, Rindra; Lasry, Estrella; Fanello, Caterina; Onyamboko, Marie; Schramm, Birgit; Yah, Zolia; Jones, Joel; Fairhurst, Rick M; Diakite, Mahamadou; Malenga, Grace; Molyneux, Malcolm; Rwagacondo, Claude; Obonyo, Charles; Gadisa, Endalamaw; Aseffa, Abraham; Loolpapit, Mores; Henry, Marie-Claire; Dorsey, Grant; John, Chandy; Sirima, Sodiomon B; Barnes, Karen I; Kremsner, Peter; Day, Nicholas P; White, Nicholas J; Mukaka, Mavuto

2018-01-18

In 2012, the World Health Organization recommended blocking the transmission of Plasmodium falciparum with single low-dose primaquine (SLDPQ, target dose 0.25 mg base/kg body weight), without testing for glucose-6-phosphate dehydrogenase deficiency (G6PDd), when treating patients with uncomplicated falciparum malaria. We sought to develop an age-based SLDPQ regimen that would be suitable for sub-Saharan Africa. Using data on the anti-infectivity efficacy and tolerability of primaquine (PQ), the epidemiology of anaemia, and the risks of PQ-induced acute haemolytic anaemia (AHA) and clinically significant anaemia (CSA), we prospectively defined therapeutic-dose ranges of 0.15-0.4 mg PQ base/kg for children aged 1-5 years and 0.15-0.5 mg PQ base/kg for individuals aged ≥6 years (therapeutic indices 2.7 and 3.3, respectively). We chose 1.25 mg PQ base for infants aged 6-11 months because they have the highest rate of baseline anaemia and the highest risks of AHA and CSA. We modelled an anthropometric database of 661,979 African individuals aged ≥6 months (549,127 healthy individuals, 28,466 malaria patients and 84,386 individuals with other infections/illnesses) by the Box-Cox transformation power exponential and tested PQ doses of 1-15 mg base, selecting dosing groups based on calculated mg/kg PQ doses. From the Box-Cox transformation power exponential model, five age categories were selected: (i) 6-11 months (n = 39,886, 6.03%), (ii) 1-5 years (n = 261,036, 45.46%), (iii) 6-9 years (n = 20,770, 3.14%), (iv) 10-14 years (n = 12,155, 1.84%) and (v) ≥15 years (n = 328,132, 49.57%) to receive 1.25, 2.5, 5, 7.5 and 15 mg PQ base for corresponding median (1st and 99th centiles) mg/kg PQ base of: (i) 0.16 (0.12-0.25), (ii) 0.21 (0.13-0.37), (iii) 0.25 (0.16-0.38), (iv) 0.26 (0.15-0.38) and (v) 0.27 (0.17-0.40). The proportions of individuals predicted to receive optimal therapeutic PQ doses were: 73.2 (29,180/39,886), 93.7 (244

Double modulation of 5-fluorouracil by methotrexate and high-dose L-leucovorin in advanced colorectal cancer.

Science.gov (United States)

Romero, A O; Perez, J E; Cuevas, M A; Lacava, J A; Sabatini, C L; Dominguez, M E; Rodriguez, R; Barbieri, M R; Ortiz, E H; Salvadori, M A; Acuña, L A; Acuña, J M; Langhi, M J; Amato, S; Machiavelli, M R; Leone, B A; Vallejo, C T; Lorusso, V; DeLena, M

1998-02-01

A phase II trial was performed to evaluate the efficacy and toxicity of a double modulation of 5-fluorouracil (5-FU) by methotrexate (MTX) and L-leucovorin (L-LV) in patients with advanced recurrent (inoperable) or metastatic colorectal carcinoma (ACC). Between July 1993 and October 1995, 41 patients with ACC received a regimen that consisted of MTX 150 mg/m2 i.v., infused over a 20-minute period at hour 0, followed 19 hours later by L-LV 250 mg/m2 in a 2-hour i.v. infusion. 5-FU, 900 mg/m2, was administered by i.v. push injection at hour 20. Beginning 24 hours after MTX administration, all patients received four doses of L-LV, 15 mg/m2 i.m., every 6 hours. Cycles were repeated every 15 days. Two patients were not assessable for response. Objective regression was observed in 11 of 39 (28%) patients, [95% confidence interval (CI), 14-42%]. One (2%) patient achieved complete response (CR) and 10 (26%) partial response (PR). No change was recorded in 15 (39%) patients and progressive disease was noted in 13 (33%) patients. The median time to treatment failure was 6 months and the median survival time was 10 months. Toxicity was within acceptable limits, but one therapy-related death due to severe leukopenia was observed. The dose-limiting toxicity was mucositis. Eight episodes of grade 3 or 4 stomatitis were observed, and were responsible for dosage modifications of MTX and 5-FU. In conclusion, further in experimental and clinical studies are clearly necessary in order to design the best modulatory strategy of 5-FU.

GFR, serum creatinine and 24-hour urine protein in evaluating renal function of patients with diabetes mellitus

International Nuclear Information System (INIS)

Chi Xiaohua; Li Guiping; Liu Feng; Wang Bing; Du Li; Deng Zhifang; Li Wei

2013-01-01

Background: Diabetes nephropathy is a common complication of diabetes mellitus patients. Early detection of renal impairment can improve the quality of life of patients. Purpose: The value of total GFR, serum creatinine, 24-hour urine protein excretion in diabetes mellitus patients with renal impairment were evaluated. Methods: A retrospective analysis of 147 patients with diabetes undergoing routine renal dynamic imaging was undertaken. The cases were divided into three groups according to the illness duration: group I of not more than five years, group 2 of five to ten years, Gr.3: more than ten years. The 22 renal transplant donors were selected as the normal control group, The total GFR, serum creatinine and 24-hour urinary protein excretion of all patients were measured before the treatments, and the data were statistically analyzed. Results: There was no significant differences in renal function between the two kidneys of in the diabetes mellitus patients (P=0.536). Serum creatinine and total GFR had significant correlation (R 2 =0.762), but no significant relationship between the 24-hour urine protein and the total GFR or serum creatinine. In the early and middle times of renal function impairment, the total GFR and serum creatinine have significant difference in different time periods (P<0.05). During the mid-late times of renal function impairment, total GFR and serum creatinine have no statistically significant differences (P value is 0.781, 0.297). 24-hour urine protein quality had no statistical differences in each stage. However: the total GFR is more sensitive than the serum creatinine in evaluation of early impairing of renal function. Conclusions: There is significant correlation between serum creatinine and total GFR. Both of them can reflect the degree of diabetic renal injury, but the total GFR is more sensitive than serum creatinine in early degree. 24-hour urine protein quantitative can not evaluate the degree of impaired renal function alone

Clinical utility in the treatment of type 2 diabetes with the saxagliptin/metformin fixed combination

Directory of Open Access Journals (Sweden)

Panagoulias GS

2014-02-01

Full Text Available George S Panagoulias,1 John Doupis2,3 11st Department of Propaedeutic and Internal Medicine, Athens University Medical School, Laiko General Hospital, Athens, Greece; 2Salamis Naval Hospital, Athens, Greece; 3Diabetes Division, Iatriko Paleou Falirou Medical Center, Athens, Greece Abstract: Fixed-dose combination (FDC products represent a widely accepted approach to type 2 diabetes treatment, given that monotherapies sometimes fail to meet the treatment targets – obtaining a sustained reduction in micro- and macrovascular complications. Saxagliptin (SAXA/metformin (MET FDC tablets can be used either alone or in combination with glyburide, thiazolidinediones, or insulin. It has been proven that the SAXA/MET combination leads to a significant improvement in glycemic control compared to placebo in patients with type 2 diabetes that is inadequately controlled with MET alone. In addition, this FDC has been proven to be safe for people with diabetes mellitus and established cardiovascular disease, elderly patients, and patients with impaired renal function (>30 mL/minute, with dosage modification. Patient compliance, adherence, and persistence to the therapeutic regimen has been shown to be very good, while the titration of each compound according to the patient's profile is easy, given the availability of different formulations. The SAXA/MET FDC is a patient-friendly, dosage-flexible, and hypoglycemia-safe regimen with very few adverse events and a neutral or even favorable effect on body weight. It achieves significant glycosylated hemoglobin A1c reduction helping the patient to achieve his/her individual glycemic goals. Keywords: DPP-4 inhibitors, saxagliptin, metformin, fixed-dose combination products, FDC products

Determination of neutron dose from criticality accidents with bioassays for sodium-24 in blood and phosphorus-32 in hair

International Nuclear Information System (INIS)

Feng, Y.; Miller, L.F.; Brown, K.S.; Casson, W.H.; Mei, G.T.; Thein, M.

1993-06-01

A comprehensive review of accident neutron dosimetry using blood and hair analysis was performed and is summarized in this report. Experiments and calculations were conducted at Oak Ridge National Laboratory (ORNL) and the University of Tennessee (UT) to develop measurement techniques for the activity of 24 Na in blood and 32 P in hair for nuclear accident dosimetry. An operating procedure was established for the measurement of 24 Na in blood using an HPGe detector system. The sensitivity of the measurement for a 20-mL sample is 0.01-0.02 Gy of total neutron dose for hard spectra and below 0.005 Gy for soft spectra based on a 30- to 60-min counting time. The operating procedures for direct counting of hair samples are established using a liquid scintillation detector. Approximately 0.06-0.1 Gy of total neutron dose can be measured from a 1-g hair sample using this procedure. Detailed procedures for chemical dissolution and ashing of hair samples are also developed. A method is proposed to use blood and hair analysis for assessing neutron dose based on a collection of 98 neutron spectra. Ninety-eight blood activity-to-dose conversion factors were calculated. The calculated results for an uncollided fission spectrum compare favorably with previously published data for fission neutrons. This nuclear accident dosimetry system makes it possible to estimate an individual's neutron dose within a few hours after an accident if the accident spectrum can be approximated from one of 98 tabulated neutron spectrum descriptions. If the information on accident and spectrum description is not available, the activity ratio of 32 P in hair and 24 Na in blood can provide information related to the neutron spectrum for dose assessment

24-Hour protein, arginine and citrulline metabolism in fed critically ill children – a stable isotope tracer study

Science.gov (United States)

de Betue, Carlijn T.I.; Garcia Casal, Xiomara C.; van Waardenburg, Dick A.; Schexnayder, Stephen M.; Joosten, Koen F.M.; Deutz, Nicolaas E.P.; Engelen, Marielle P.K.J.

2017-01-01

Background & aims The reference method to study protein and arginine metabolism in critically ill children is measuring plasma amino acid appearances with stable isotopes during a short (4–8h) time period and extrapolate results to 24-hour. However, 24-hour measurements may be variable due to critical illness related factors and a circadian rhythm could be present. Since only short duration stable isotope studies in critically ill children have been conducted before, the aim of this study was to investigate 24-hour appearance of specific amino acids representing protein and arginine metabolism, with stable isotope techniques in continuously fed critically ill children. Methods In eight critically ill children, admitted to the pediatric (n=4) or cardiovascular (n=4) intensive care unit, aged 0–10 years, receiving continuous (par)enteral nutrition with protein intake 1.0–3.7 g/kg/day, a 24-hour stable isotope tracer protocol was carried out. L-[ring-2H5]-phenylalanine, L-[3,3-2H2]-tyrosine, L-[5,5,5-2H3]-leucine, L-[guanido-15N2]-arginine and L-[5-13C-3,3,4,4-2H4]-citrulline were infused intravenously and L-[15N]-phenylalanine and L-[1-13C]leucine enterally. Arterial blood was sampled every hour. Results Coefficients of variation, representing intra-individual variability, of the amino acid appearances of phenylalanine, tyrosine, leucine, arginine and citrulline were high, on average 14–19% for intravenous tracers and 23–26% for enteral tracers. No evident circadian rhythm was present. The pattern and overall 24-hour level of whole body protein balance differed per individual. Conclusions In continuously fed stable critically ill children, the amino acid appearances of phenylalanine, tyrosine, leucine, arginine and citrulline show high variability. This should be kept in mind when performing stable isotope studies in this population. There was no apparent circadian rhythm. PMID:28089618

Fasting for 24 hours heightens reward from food and food-related cues.

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Cameron, Jameason D; Goldfield, Gary S; Finlayson, Graham; Blundell, John E; Doucet, Eric

2014-01-01

We examined the impact of a 24 hour complete fast (vs. fed state) on two measures of food reward: 1) 'wanting', as measured by response to food images and by the relative-reinforcing value of food (RRV), and 2) 'liking', as measured by response to food images and the hedonic evaluation of foods consumed. Utilizing a randomized crossover design, 15 subjects (9 male; 6 female) aged 28.6±4.5 yrs with body mass index 25.3±1.4 kg/m(2) were randomized and counterbalanced to normal feeding (FED) and 24-hour fast (FASTED) conditions. Trait characteristics were measured with the Three Factor Eating Questionnaire. Two computer tasks measured food reward: 1) RRV progressive ratio task, 2) explicit 'liking' and 'wanting' (Leeds Food Preference Questionnaire, LFPQ). Also measured were ad libitum energy intake (EI; buffet) and food 'liking' (visual analogue scale) of personalized stimuli. There were no significant anthropometric changes between conditions. Appetite scores, hedonic ratings of 'liking', and ad libitum EI all significantly increased under the FASTED condition (pFASTED condition there were significant increases in the RRV of snack foods; similarly, explicit 'wanting' and 'liking' significantly increased for all food categories. 'Liking' of sweet foods remained high across-meals under FASTED, but savory foods decreased in hedonic saliency. Relative to a fed state, we observed an increase in hedonic ratings of food, the rewarding value of food, and food intake after a 24 hr fast. Alliesthesia to food and food cues is suggested by heightened hedonic ratings under the FASTED condition relative to FED.

No impact of dietary iodine restriction in short term development of hypothyroidism following fixed dose radioactive iodine therapy for Graves' disease.

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Jacob, Jubbin Jagan; Stephen, Charles; Paul, Thomas V; Thomas, Nihal; Oommen, Regi; Seshadri, Mandalam S

2015-01-01

The increased incidence of autoimmune thyroid disease with increasing dietary iodine intake has been demonstrated both epidemiologically and experimentally. The hypothyroidism that occurs in the first year following radioactive iodine therapy is probably related to the destructive effects of the radiation and underlying ongoing autoimmunity. To study the outcomes at the end of six months after fixed dose I, (131)therapy for Graves' disease followed by an iodine restricted diet for a period of six months. Consecutive adult patients with Graves' disease planned for I(131) therapy were randomized either to receive instructions regarding dietary iodine restriction or no advice prior to fixed dose (5mCi) I(131) administration. Thyroid functions and urinary iodine indices were evaluated at 3(rd) and 6(th) month subsequently. Forty seven patients (13M and 34F) were assessed, 2 were excluded, 45 were randomized (Cases 24 and Controls 21) and 39 patients completed the study. Baseline data was comparable. Median urinary iodine concentration was 115 and 273 μg/gm creat (p = 0.00) among cases and controls respectively. Outcomes at the 3(rd) month were as follows (cases and controls); Euthyroid (10 and 6: P = 0.24), Hypothyroid (3 and 5: P = 0.38) and Hyperthyroid (7 and 8: P = 0.64). Outcomes at the end of six months were as follows (cases and controls); Euthyroid (10 and 5: P = 0.12), Hypothyroid (3 and 5: P = 0.38) and Hyperthyroid (7 and 9: P = 0.43). Of the hypothyroid patients 5 (cases 1 and controls 4: P = 0.13) required thyroxine replacement. There was no statistical significant difference in the outcome of patients with dietary iodine restriction following I(131) therapy for Graves' disease.

Bioequivalence assessment of rifampicin, isoniazid and pyrazinamide in a fixed dose combination of rifampicin, isoniazid, pyrazinamide and ethambutol vs. separate formulations.

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Agrawal, S; Singh, I; Kaur, K J; Bhade, S R; Kaul, C L; Panchagnula, R

2002-10-01

Depending on the patient category, tuberculosis requires treatment with 3 to 5 drugs which means that patient's compliance to therapy may not be optimal. To increase patient's adherence to treatment schedules, these drugs can be given as single drug preparations or fixed dose combinations (FDCs) of 2 or more drugs in a single formulation. However, an important issue associated with a rifampicin-containing FDC is its quality. Hence, to avoid spurious formulations entering the market, the World Health Organization and the International Union Against Tuberculosis and Lung Disease have recommended FDCs only of proven bioavailability. In this study, the relative bioavailability of rifampicin, isoniazid and pyrazinamide was assessed in a group of 14 healthy male subjects using the FDC tablet containing 4 drugs versus separate formulations at the same dose levels. The study was designed as an open, crossover trial. A total of 9 blood samples were collected over a period of 24 h. The concentration of rifampicin, its main metabolite desacetyl rifampicin, isoniazid and pyrazinamide in plasma were assessed using HPLC analysis. The pharmacokinetic parameters AUC(0-24) and Cmax were subjected to parametric and non-parametric statistical tests at 90% confidence interval. In addition, time to reach peak concentration (tmax), elimination rate constant (Kel) and terminal elimination half-life (t1/2) for each drug were also calculated. It was concluded that the FDC tablet containing 4 drugs is bioequivalent to separate rifampicin, isoniazid and pyrazinamide formulations at the same dose levels.

Fixed-Dose Combination Gel of Adapalene and Benzoyl Peroxide plus Doxycycline 100 mg versus Oral Isotretinoin for the Treatment of Severe Acne: Efficacy and Cost Analysis.

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Penna, Pete; Meckfessel, Matthew H; Preston, Norman

2014-01-01

Acne vulgaris is a chronic skin disease with a high prevalence. Left untreated or inadequately treated, acne vulgaris can lead to psychological and physical scarring, as well as to unnecessary medical expenses. Oral isotretinoin is an effective treatment for severe resistant nodular and conglobate acne vulgaris. A regimen consisting of a fixed-dose combination of adapalene and benzoyl peroxide gel, 0.1%/2.5% (A-BPO) with oral doxycycline 100 mg (A-BPO/D) has been demonstrated to be efficacious and well tolerated in patients with severe acne and may be an alternative to oral isotretinoin for some patients with severe acne. The objective of this analysis was to compare the relative efficacy and associated costs of A-BPO/D versus oral isotretinoin. In this analysis, comparisons of relative efficacy were made using previously published studies involving similar patient populations with severe acne that warrant the use of oral isotretinoin. The pricing for oral doxycycline and oral isotretinoin was estimated based on the maximum allowable cost from 9 states, and the pricing for A-BPO was calculated as the range between the average wholesale price and the wholesale acquisition cost. For this analysis, 2 treatment models were generated to compare costs: (1) a basic treatment model that examined the costs of an initial regimen of either A-BPO/D or oral isotretinoin without considering probable outcomes, and (2) a long-term model that factored in likely treatment outcomes and subsequent treatments into associated costs. The basic treatment model assumed that patients would be prescribed a single regimen of A-BPO/D for 12 weeks or oral isotretinoin for 20 weeks. The long-term model considered the probability of each treatment successfully managing patients' acne, as well as likely additional regimens of A-BPO monotherapy or an additional regimen of oral isotretinoin. As a result of different treatment durations, the costs for each treatment were normalized to weekly cost of

Individualized Ranibizumab Regimen Driven by Stabilization Criteria for Central Retinal Vein Occlusion

DEFF Research Database (Denmark)

Larsen, Michael; Waldstein, Sebastian M; Boscia, Francesco

2016-01-01

ischemia (exploratory analysis). RESULTS: At baseline, the mean BCVA was 53.0 letters and mean CRVO duration was 8.9 months (median, 2.4 months). Ranibizumab 0.5-mg treatment resulted in a statistically significant mean gain in BCVA from baseline at month 12 of 12.3 letters (standard deviation [SD], 16......PURPOSE: To assess the 12-month efficacy and safety profile of an individualized regimen of ranibizumab 0.5 mg driven by stabilization criteria in patients with macular edema secondary to central retinal vein occlusion (CRVO). DESIGN: A 24-month, prospective, open-label, single-arm, multicenter...... study. PARTICIPANTS: Three hundred fifty-seven patients. METHODS: Patients were treated with monthly ranibizumab 0.5-mg injections (minimum of 3 injections) until stable visual acuity (VA) was maintained for 3 consecutive months. Thereafter, ranibizumab 0.5 mg was dosed as needed if monthly monitoring...

Pharmacodynamic evaluation of intragastric pH and implications for famotidine dosing in the prophylaxis of non-steroidal anti-inflammatory drug induced gastropathy-a proof of concept analysis.

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Kent, Jeffery D; Holt, Robert J; Jung, Donald; Tidmarsh, George F; Grahn, Amy Y; Ball, Julie; Peura, David A

2014-01-01

Famotidine given at a dose of 80 mg/day is effective in preventing NSAID-induced gastropathy. The aim of this proof of concept study was to compare twice a day (BID) vs 3-times a day (TID) administration of this total dose of famotidine on intragastric pH in healthy volunteers. Two analyses were undertaken: (1) a 13 subject controlled cross-over 24-h intragastric pH evaluation of the BID and TID administration of 80 mg/day of famotidine, as well as measures for drug accumulation over 5 days (EudraCT, number 2006-002930-39); and (2) a pharmacokinetic (PK)/pharmacodynamic (PD) model which predicted steady-state famotidine plasma concentrations and pH of the two regimens. For the cross-over study, gastric pH was above 3.5 for a mean of 20 min longer for TID dosing compared to BID dosing on Day 1. On Day 5, the mean time above this threshold was higher with the BID regimen by ∼25 min. For pH 4, subjects' gastric pH was above this pH value for a mean of 25 min longer for TID dosing compared to BID dosing on Day 1. For Day 5, the pH was above 4 for ∼45 min longer with the TID regimen as compared with the BID regimen. The mean 24-h gastric pH values when taken in the upright position trended higher for the TID dosing period compared to the BID regimen on Day 1. The steady-state simulation model indicated that, following TID dosing, intragastric pH will be above 3 for 24 h vs 16 h for the BID regimen. There was no evidence for plasma accumulation of famotidine with TID dosing as compared to BID dosing from either analysis. The data indicate that overall more time is spent above the acidic threshold pH values when 80 mg/day of famotidine is administered TID vs BID. Key limitations included small study size with a short duration and lack of a baseline examination, but was compensated for by the cross-over and PK/PD modeling design. Although most of the comparisons in this proof of concept study were not statistically significant these results have

Control of hypertension with single daily doses of sotalol hydrochloride.

Science.gov (United States)

Gabriel, R

A study was carried out in 12 previously untreated hypertensive patients to assess the efficacy of sotalol given in a once-daily dosage regimen. After an initial dosage titration period (mean 3 weeks) during which diastolic pressure was stabilized at less than 100 mmHg, all patients were satisfactorily maintained on a constant once-daily dose of sotalol for 3 months. Eight of the 12 patients required 320 mg or less daily (mean dose 190 mg). Whilst blood pressure remained controlled for at least 26 hours after daily doses the pulse rate, counted at the same time, showed escape from beta-blockade. Side-effects (vivid dreams) were reported in only 1 patient.

Knemometry is more sensitive to systemic effects of inhaled corticosteroids in children with asthma than 24-hour urine cortisol excretion

DEFF Research Database (Denmark)

Chawes, Bo; Nilsson, Erik; Nørgaard, Sarah

2017-01-01

Background: Pharmacodynamic assessment of the systemic effect of inhaled corticosteroids (ICSs) is often done by measuring 24-hour urine free cortisol (UFC) excretion. Knemometry assessing short-term lower-leg growth rate (LLGR) is a more rarely used alternative. Objective: The primary aim...... of this study was to compare the sensitivity of LLGR and 24-hour UFC excretion for evaluating systemic exposure to ICSs in prepubertal children with asthma. The secondary aim was to evaluate factors influencing the precision of LLGR calculated by the traditional 1 leg nonparametric method versus a new 2 leg...... parametric method. Methods: The study evaluated 60 children with mild asthma aged 5 to 12 years participating in a randomized controlled trial of ICSs with longitudinal concomitant assessments of LLGR and 24-hour UFC excretion. The sensitivity of the safety assessments was analyzed by comparing LLGR and 24...

Legal, ethical, and economic implications of breaking down once-daily fixed-dose antiretroviral combinations into their single components for cost reduction.

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Ramiro, Miguel A; Llibre, Josep M

2014-11-01

The availability of generic lamivudine in the context of the current economic crisis has raised a new issue in some European countries: breaking up the once-daily fixed-dose antiretroviral combinations (FDAC) of efavirenz/tenofovir/emtricitabine, tenofovir/emtricitabine, or abacavir/lamivudine, in order to administer their components separately, thereby allowing the use of generic lamivudine instead of branded emtricitabine or lamivudine. The legal, ethical, and economic implications of this potential strategy are reviewed, particularly in those patients receiving a once-daily single-tablet regimen. An unfamiliar change in antiretroviral treatment from a successful patient-friendly FDAC into a more complex regimen including separately the components to allow the substitution of one (or some) of them for generic surrogates (in the absence of a generic bioequivalent FDAC) could be discriminatory because it does not guarantee access to equal excellence in healthcare to all citizens. Furthermore, it could violate the principle of non-maleficence by potentially causing harm both at the individual level (hindering adherence and favouring treatment failure and resistance), and at the community level (hampering control of disease transmission and transmission of HIV-1 resistance). Replacing a FDAC with the individual components of that combination should only be permitted when the substituting medication has the same qualitative and quantitative composition of active ingredients, pharmaceutical form, method of administration, dosage and presentation as the medication being replaced, and a randomized study has demonstrated its non-inferiority. Finally, a strict pharma-economic study supporting this change, comparing the effectiveness and the cost of a specific intervention with the best available alternative, should be undertaken before its potential implementation. Copyright © 2013 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiolog

Optimization of the fractionated irradiation scheme considering physical doses to tumor and organ at risk based on dose–volume histograms

Energy Technology Data Exchange (ETDEWEB)

Sugano, Yasutaka [Graduate School of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-ku, Sapporo, Hokkaido 060-0812 (Japan); Mizuta, Masahiro [Laboratory of Advanced Data Science, Information Initiative Center, Hokkaido University, Kita-11, Nishi-5, Kita-ku, Sapporo, Hokkaido 060-0811 (Japan); Takao, Seishin; Shirato, Hiroki; Sutherland, Kenneth L. [Department of Radiation Medicine, Graduate School of Medicine, Hokkaido University, Kita-15, Nishi-5, Kita-ku, Sapporo, Hokkaido 060-8638 (Japan); Date, Hiroyuki, E-mail: date@hs.hokudai.ac.jp [Faculty of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-ku, Sapporo, Hokkaido 060-0812 (Japan)

2015-11-15

Purpose: Radiotherapy of solid tumors has been performed with various fractionation regimens such as multi- and hypofractionations. However, the ability to optimize the fractionation regimen considering the physical dose distribution remains insufficient. This study aims to optimize the fractionation regimen, in which the authors propose a graphical method for selecting the optimal number of fractions (n) and dose per fraction (d) based on dose–volume histograms for tumor and normal tissues of organs around the tumor. Methods: Modified linear-quadratic models were employed to estimate the radiation effects on the tumor and an organ at risk (OAR), where the repopulation of the tumor cells and the linearity of the dose-response curve in the high dose range of the surviving fraction were considered. The minimization problem for the damage effect on the OAR was solved under the constraint that the radiation effect on the tumor is fixed by a graphical method. Here, the damage effect on the OAR was estimated based on the dose–volume histogram. Results: It was found that the optimization of fractionation scheme incorporating the dose–volume histogram is possible by employing appropriate cell surviving models. The graphical method considering the repopulation of tumor cells and a rectilinear response in the high dose range enables them to derive the optimal number of fractions and dose per fraction. For example, in the treatment of prostate cancer, the optimal fractionation was suggested to lie in the range of 8–32 fractions with a daily dose of 2.2–6.3 Gy. Conclusions: It is possible to optimize the number of fractions and dose per fraction based on the physical dose distribution (i.e., dose–volume histogram) by the graphical method considering the effects on tumor and OARs around the tumor. This method may stipulate a new guideline to optimize the fractionation regimen for physics-guided fractionation.

Pharmacokinetics and bioequivalence study of a fixed dose combination of rabeprazole and itopride in healthy Indian volunteers.

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Sahoo, Bijay Kumar; Das, Ayan; Agarwal, Sangita; Bhaumik, Uttam; Bose, Anirbandeep; Ghosh, Debotri; Roy, Bikash; Pal, Tapan Kumar

2009-01-01

The aim of the present study was to compare the pharmacokinetics of rabeprazole (CAS 117976-89-3) and itopride (CAS 122898-67-3) after oral administration of a rabeprazole (20 mg)-itopride (150 mg) fixed dose combination (FDC) in healthy human volunteers. The bioequivalence of two formulations (test and reference) was determined in 12 healthy Indian male volunteers (age: 25.25 +/- 4.69 years; weight: 60.50 +/- 5.04 kg) in a randomized, single-dose, two-period, two-treatment crossover study. Both formulations were administered orally as a single dose, with the treatments separated by a washout period of 1 week. Rabeprazole and itopride plasma levels were determined by a validated HPLC method using UV detection. The formulations were compared using the pharmacokinetic parameters area under the plasma concentration-time curve (AUC(0-t)), area under the plasma concentration-time curve from zero to infinity (AUC(0-infinity)) and peak plasma concentration (Cmax). General linear model (GLM) procedures were used in which sources of variation were subject, treatment and period. The results indicated that there were no statistically significant differences (P > 0.05) between the logarithmically transformed AUC(0-infinity) and Cmax values between test and reference formulation. The 90% confidence interval for the ratio of the logarithmically transformed AUC(0-t), AUC(0-infinity) and Cmax were within the bioequivalence limits of 0.8-1.25 and the relative bioavailability of rabeprazole and itopride test and reference formulations was 98.24 and 93.65%, respectively.

The role of a low-dose ketamine-midazolam regimen in the management of severe painful crisis in patients with sickle cell disease.

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Tawfic, Qutaiba A; Faris, Ali S; Kausalya, Rajini

2014-02-01

Acute pain is one of the main causes of hospital admission in sickle cell disease, with variable intensity and unpredictable onset and duration. We studied the role of a low-dose intravenous (IV) ketamine-midazolam combination in the management of severe painful sickle cell crisis. A retrospective analysis was performed with data from nine adult patients who were admitted to the intensive care unit with severe painful sickle cell crises not responding to high doses of IV morphine and other adjuvant analgesics. A ketamine-midazolam regimen was added to the ongoing opioids as an initial bolus of ketamine 0.25mg/kg, followed by infusion of 0.2-0.25mg/kg/h. A midazolam bolus of 1mg followed by infusion of 0.5-1mg/h was added to reduce ketamine emergence reactions. Reduction in morphine daily requirements and improvement in pain scores were the determinants of ketamine-midazolam effect. The t-tests were used for statistical analysis. Nine patients were assessed, with mean age of 27±11 years. Morphine requirement was significantly lower after adding the IV ketamine-midazolam regimen. The mean±SD IV morphine requirement (milligram/day) in the pre-ketamine day (D0) was 145.6±16.5, and it was 112±12.2 on Day 1 (D1) of ketamine treatment (P=0.007). The Numeric Rating Scale scores on D0 ranged from eight to ten (mean 9.1), but improved to range from five to seven (mean 5.7) on D1. There was a significant improvement in pain scores after adding ketamine-midazolam regimen (P=0.01). Low-dose ketamine-midazolam IV infusion might be effective in reducing pain and opioid requirements in patients with sickle cell disease with severe painful crisis. Further controlled studies are required to prove this effect. Copyright © 2014 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

Delayed rhabdomyolysis with paclitaxel, ifosfamide, carboplatin, and etoposide regimen: a case report.

Science.gov (United States)

Sokolova, Alexandra; Chan, Onyee; Ullah, Waqas; Hamdani, Auon Abbas; Anwer, Faiz

2017-04-11

High-dose chemotherapy with autologous stem cell rescue is commonly used for the treatment of relapsed germ cell tumors. We report the first case of delayed rhabdomyolysis with paclitaxel, ifosfamide, carboplatin, and etoposide regimen. We report a case of a 21-year-old African-American man diagnosed with relapsed non-seminomatous germ cell tumor who received high-dose chemotherapy with carboplatin and etoposide following TIGER trial arm B off-protocol. His course was complicated by muscle pain and rhabdomyolysis after cycle 4 on day +12 after infusion of autologous stem cells. To the best of our knowledge, this complication has not been reported with this regimen. A differential diagnosis of sepsis and neutropenic fever along with side effects of high-dose chemotherapy were considered, but based on the timing of events, it was concluded that the etiology of rhabdomyolysis is high-dose chemotherapy. Rhabdomyolysis was successfully treated with hydration and did not recur during subsequent cycle 5. Delayed rhabdomyolysis after high-dose chemotherapy with paclitaxel, ifosfamide, carboplatin, and etoposide regimen has not been previously reported and needs to be considered for preventive strategy and prompt diagnosis and treatment to avoid renal complications. Physicians should have a low threshold to check creatine kinase enzymes in patients with unexplained muscle pain or renal insufficiency after high-dose chemotherapy.

Efficacy and safety of a therapeutic interchange from high-dose calcium channel blockers to a fixed-dose combination of amlodipine/benazepril in patients with moderate-to-severe hypertension.

Science.gov (United States)

Hilleman, D E; Reyes, A P; Wurdeman, R L; Faulkner, M

2001-08-01

Recent hypertension trials have demonstrated the importance of achieving goal blood pressures to reduce the risk of target organ damage. In patients with moderate to severe hypertension, the use of high-dose monotherapy and/or combinations of drugs are necessary to achieve these goals. Fixed-dose combination products may be useful in these patients by reducing the number of daily doses required to control blood pressure. The objective of the present study was to evaluate the efficacy and safety of a therapeutic interchange between high-dose calcium channel blocker therapy and a fixed-dose combination of amlodipine/ benazepril (Lotrel; Novartis Pharmaceuticals, USA) in patients with moderate to severe hypertension. A total of 75 patients were switched from amlodipine (n = 25), felodipine (n = 25), and nifedipine-GITS (n = 25) to amlodipine/benazepril. Twenty-eight of the 75 patients (37%) were taking either a beta-blocker or a diuretic in addition to the high-dose calcium channel blocker prior to the switch. Blood pressure control, side effects and the cost of the therapeutic interchange were evaluated in the year following the therapeutic interchange. Sixty-six of the 75 (88%) patients were successfully switched with maintenance of blood pressure control and without the development of new dose-limiting side effects. Reasons for treatment failure after the therapeutic interchange included loss of blood pressure control in five patients and the development of new dose-limiting side effects in four patients. These side effects included cough in three patients and rash in one patient. After accounting for differences in drug acquisition cost and costs related to the switch (clinic and emergency room and laboratory tests), a cost savings of $16030 for all 75 patients was realised in the first year. The per patient-per year cost savings was $214. Our data indicate that a therapeutic interchange from selected high-dose calcium channel blockers to a fixed-dose combination