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Sample records for fixed weight-based dose

  1. Review of current evidence available for guiding optimal Enoxaparin prophylactic dosing strategies in obese patients-Actual Weight-based vs Fixed.

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    He, Zikai; Morrissey, Hana; Ball, Patrick

    2017-05-01

    The current debate over the optimal Enoxaparin prophylactic dosing strategies in obese patients centre around whether it should be based on the actual weight of the patient (i.e. weight-based), or at an artificially fixed amount, as it is the case in Australia (40mg daily). The vast majority of the evidence available today is laboratory-based, measuring serum Antifactor-Xa activities as a marker for physiological response. The aim of the parent study is to compare the clinical outcomes for obese patients who received fixed doses of enoxaparin compared to those who received weight-based doses within the licensed dosage recommendations. This review was conducted to examine whether a gap in knowledge exists in relation to dosing obese patients with enoxaparin as VTE prophylaxis after hospital admission to aid in development of the parent study concept. Databases such as Medline, EBSCOhost, ProQuest were interrogated using combinations of words such as "enoxaparin", AND "dosing strategy", AND "obese/obesity" AND "prophylaxis". Only eleven out of 14 primary studies which were considered to be sufficiently similar in methodology and anticipated outcomes were reviewed and analysed. Pooled data from the eleven studies suggested that weight-based or higher-than-fixed dosing had a 36.2% higher success rate than fixed dosing, and was more likely to achieve the desired serum Anti-Xa activity levels (52.2% and 16% respectively). The rate of failure to achieve this is significantly lower in the weight-based groups (13.3%) than in fixed-dose groups (18.5%). These eleven studies reviewed included 601 patients in total. There is insufficient evidence to support or negate the current enoxaparin health outcomes in obese and very obese patients due to the lack of post-discharge follow-up from hospitals. Further research is required to compare long-term outcomes after fixed and weight-based dosing of enoxaparin. The optimal dose of enoxaparin per kilogram of body weight for prophylaxis

  2. Effect of Fixed-Volume and Weight-Based Dosing Regimens on the Cost and Volume of Administered Iodinated Contrast Material at Abdominal CT.

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    Davenport, Matthew S; Parikh, Kushal R; Mayo-Smith, William W; Israel, Gary M; Brown, Richard K J; Ellis, James H

    2017-03-01

    To determine the magnitude of subject-level and population-level cost savings that could be realized by moving from fixed-volume low-osmolality iodinated contrast material administration to an effective weight-based dosing regimen for contrast-enhanced abdominopelvic CT. HIPAA-compliant, institutional review board-exempt retrospective cohort study of 6,737 subjects undergoing contrast-enhanced abdominopelvic CT from 2014 to 2015. Subject height, weight, lean body weight (LBW), and body surface area (BSA) were determined. Twenty-six volume- and weight-based dosing strategies with literature support were compared with a fixed-volume strategy used at the study institution: 125 mL 300 mgI/mL for routine CT, 125 mL 370 mgI/mL for multiphasic CT (single-energy, 120 kVp). The predicted population- and subject-level effects on cost and contrast material utilization were calculated for each strategy and sensitivity analyses were performed. Most subjects underwent routine CT (91% [6,127/6,737]). Converting to lesser-volume higher-concentration contrast material had the greatest effect on cost; a fixed-volume 100 mL 370 mgI/mL strategy resulted in $132,577 in population-level savings with preserved iodine dose at routine CT (37,500 versus 37,000 mgI). All weight-based iodine-content dosing strategies (mgI/kg) with the same maximum contrast material volume (125 mL) were predicted to contribute mean savings compared with the existing fixed-volume algorithm ($4,053-$116,076/strategy in the overall study population, $1-$17/strategy per patient). Similar trends were observed in all sensitivity analyses. Large cost and material savings can be realized at abdominopelvic CT by adopting a weight-based dosing strategy and lowering the maximum volume of administered contrast material. Copyright © 2016 American College of Radiology. Published by Elsevier Inc. All rights reserved.

  3. A randomized controlled trial of darbepoetin alfa administered as a fixed or weight-based dose using a front-loading schedule in patients with anemia who have nonmyeloid malignancies.

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    Hesketh, Paul J; Arena, Francis; Patel, Dhimant; Austin, Matt; D'Avirro, Paul; Rossi, Gregory; Colowick, Alan; Schwartzberg, Lee; Bertoli, Luigi F; Cole, John T; Demetri, George; Dessypris, Emmanuel; Dobbs, Tracy; Eisenberg, Peter; Fleischman, Roger; Hall, James; Hoffman, Phillip C; Laber, Damian A; Leonard, John; Lester, Eric P; McCachren, Spence; McMeekin, Scott; Meza, Luis; Miller, David Scott; Nand, Sucha; Oliff, Ira; Paroly, Warren; Pawl, Larry; Perez, Alejandra; Raftopoulos, Harry; Rigas, James; Rowland, Kendrith; Scullin, Daniel C; Tezcan, Haluk; Waples, John; Ward, John; Yee, Lorrin K

    2004-02-15

    The effect of using fixed versus weight-based doses for erythropoietic agents has not been reported previously. To investigate this issue, the authors conducted a randomized Phase II study of darbepoetin alfa administered as either a fixed dose or a weight-based dose using an accelerated correction and maintenance dosing regimen (front-loading). During the correction phase, patients with anemia (hemoglobin or = 12.0 g/dL. Patients then received darbepoetin alfa (325 microg or 4.5 microg/kg) once every 3 weeks for the remainder of the 16-week treatment period (maintenance phase). Darbepoetin alfa resulted in high Kaplan-Meier rates of hematopoietic response (> or = 2 g/dL increase from the baseline level or a hemoglobin level > or = 12 g/dL) in both the fixed-dose group (86%; 95% confidence interval [95% CI], 78- 94%) and the weight-based dose group (84%; 95% CI, 76-92%). The median time to hematopoietic response was 34 days (95% CI, 28-44 days) for the fixed-dose group and 36 days (95% CI, 30-45 days) for the weight-based dose group. Hemoglobin concentrations were maintained at target levels for up to 16 weeks in both groups. Darbepoetin alfa was well tolerated, and no clinically significant differences between fixed doses and weight-based doses were observed. Darbepoetin alfa was effective when administered as either a fixed dose or a weight-based dose using a front-loading approach to rapidly correct anemia and effectively maintain hemoglobin levels in patients with anemia who had malignant disease. Copyright 2004 American Cancer Society.

  4. Simple weight-based contrast dosing for standardization of portal phase CT liver enhancement

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    Benbow, M. [Department of Radiology, Royal Bournemouth Hospital, Bournemouth, Dorset (United Kingdom); Bull, R.K., E-mail: russell.bull@rbch.nhs.uk [Department of Radiology, Royal Bournemouth Hospital, Bournemouth, Dorset (United Kingdom)

    2011-10-15

    Aim: To investigate the use of a weight-based volume of contrast media to optimize portal enhancement in patients undergoing abdominal computed tomography (CT). Materials and methods: Thirty-one patients were assessed to establish whether a relationship existed between their weight and the portal liver enhancement achieved. Three methods of estimating weight were evaluated to establish which was the most appropriate to use in clinical practice. One hundred patients were then examined using 100 ml contrast media and 100 further patients using a weight-based contrast volume as dictated by a look-up table. The enhancement achieved by each technique was assessed. Results: A good correlation was shown between patient weight and contrast enhancement when a fixed volume of contrast media was used (r = -0.825, p < 0.0001). Asking the patient was shown to be the most appropriate method for estimating their weight. The mean portal liver enhancement using the fixed dose and weight-adjusted dose were 110 HU (SD = 25.1) and 108 HU (SD = 11.9), respectively. Weight-adjusted dose brought 37% more patients into the 'ideal' enhancement range of 100-125 HU. Conclusion: The use of a simple, practical, weight-based look-up table to decide contrast media volumes during portal phase liver CT can greatly reduce inter-patient variability compared to a fixed-volume technique.

  5. 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.

  6. 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

  7. Weight-Based Adaptation of TNF-Antagonist Induction versus Maintenance Dose

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    Marco A. Muster

    2011-06-01

    Full Text Available Biologics are highly specific and exhibit few problems in regard to overdosages. In clinical practice, induction schemes with an initial loading dose and a subsequent lower maintenance dose have been established and are of higher efficacy for psoriasis than starting directly with the maintenance dose. As obese patients sometimes respond less well to standard dosages, increases of the maintenance dose, but not the loading doses, have been tried with variable success. In our study, we increased the loading (160 mg instead of 80 mg but not the maintenance dose of adalimumab in an obese patient with severe psoriasis resistant to previous biologics and methotrexate. Within 12 weeks, both PASI (11 to 1.6 and DLQI (22/30 to 5/30 decreased. This strategy might be an effective and less costly alternative to doubling the maintenance doses, and could be further evaluated for psoriasis patients refractory to previous treatments.

  8. Novel weight-based dose threshold for 18F-NaF PET-CT imaging using advanced PET-CT systems: a potential tool for reducing radiation burden.

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    Marafi, Fahad; Esmail, Abdulreda; Rasheed, Rashid; Alkandari, Fareeda; Usmani, Sharjeel

    2017-09-01

    Fluorine-18-sodium fluoride (F-NaF) PET/CT is an important tool for detecting and evaluating metastatic bone cancer. Besides traditional dose metrics, recent methods such as real-time dose mapping, dose calculation from DICOM information, and their relevance to entrance skin exposure are currently in use to reduce the radiation burden. In this study, we have analyzed the data of 1062 patients retrospectively to evaluate patterns of absorbed dose for institutional weight-based dose protocol as compared with fixed dose method guidelines of Society of Nuclear Medicine and Molecular Imaging (SNMMI). The effective dose imparted by F-NaF (internal exposure) was calculated by using coefficient 0.089 mrem/mCi (0.024 mSv/MBq) according to ICRP publication 106. To estimate the effective dose from whole-body CT scan (external exposure), volume CT dose index (mGy) and dose length product (mGy cm) were directly obtained from the display screen of CT workstation. Effective dose was calculated by multiplying DLP (mGy cm) with ICRP conversion coefficient 'k' 0.015 (mSv/mGy cm). Of the total 1062 patients, there were metastases in 44% (464), probable malignancy in 9% (96), negative findings in 40.5% (433), equivocal findings in 3% (32), and probable benignancy in 3.5% (37). All patients were injected with an institutional agreed protocol of 2.22 MBq/kg (0.06 mCi/kg). The mean injected activity for entire population came out to be 4.79±0.99 mCi. The mean effective absorbed doses were 3.37±0.70 and 5.5±1.35 mSv for F-NaF alone and CT alone, respectively. The mean cumulative effective dose of combined F-NaF PET and CT scan was calculated to be 8.8±1.8 mSv. The minimum absorbed dose for our method was as follows: 1.37 mSv for Kuwait Cancer Control Center vs. 4.44 mSv for SNMMI. Absorbed dose for maximum injected activity was as follows: 5.7 mSv for Kuwait Cancer Control Center vs. 8.88 mSv for SNMMI. Our weight-based doses were also lower when compared

  9. Prescription of fixed dose combination drugs for diarrhoea.

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    Chakrabarti, Amit

    2007-01-01

    Fixed-dose combinations (FDCs) of an antiprotozoal and an antibacterial, for treatment of diarrhoea, have been available in the Indian pharmaceutical market for about a decade. There is little evidence to substantiate this combination therapy. We evaluated 2,163 physician prescriptions for diarrhoea and found that 59 per cent of prescriptions were for FDCs. This is unethical because prescribing such combinations exposes a patient to higher risks of adverse drug reactions and also increases the chances of drug resistance. Physicians' prescribing practices in India are influenced by socioeconomic factors and the pharmaceutical industry's marketing techniques that include giving incentives to physicians to prescribe certain drugs.

  10. Amlodipine/benazepril: fixed dose combination therapy for hypertension.

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    Faulkner, M A; Hilleman, D E

    2001-01-01

    Myocardial infarction, stroke, heart failure and end-stage renal disease have all been linked to inadequate control of blood pressure. Despite overwhelming evidence that uncontrolled hypertension is responsible for a sizeable number of adverse health-related outcomes, control of the disease remains considerably suboptimal. Available data demonstrate that in order to achieve adequate blood pressure control, a large number of patients require therapy with more than one medication. Fixed dose combination antihypertensive therapy has many advantages over other treatment options. Positive effects on blood pressure control, rates of adherence, adverse effects and cost have been identified. Amlodipine/benazepril (Lotrel), Novartis) is a fixed dose combination product indicated for the treatment of hypertension. Although not currently recommended as first-line therapy, studies confirm that this combination of a long-acting calcium antagonist and an angiotensin-converting enzyme (ACE) inhibitor possesses substantial blood pressure lowering capabilities. Whereas adverse events tend to become more frequent with increasing doses of antihypertensive monotherapy, the rate of adverse events attributed to amlodipine/benazepril in clinical trials often correlates with rates ascribed to placebo. Amlodipine/benazepril is capable of sustaining blood pressure control over a 24 h period and appears to be minimally affected by an occasional dose omission. Unlike the older calcium antagonists, amlodipine is unlikely to cause alterations in myocardial contractility. Additionally, the amlodipine/benazepril combination product costs less than the same therapy administered as the individual components. It is, therefore, reasonable to consider therapy with amlodipine/benazepril in appropriate patients after an adequate trial of antihypertensive monotherapy.

  11. Comparison of Body Surface Area versus Weight-Based Growth Hormone Dosing for Girls with Turner Syndrome

    NARCIS (Netherlands)

    Schrier, L.; Kam, M.L. de; McKinnon, R.; Bakri, A. Che; Oostdijk, W.; Sas, T.C.J.; Menke, L.A.; Otten, B.J.; Keizer-Schrama, S.M.; Kristrom, B.; Ankarberg-Lindgren, C.; Burggraaf, J.; Albertsson-Wikland, K.; Wit, J.M.

    2014-01-01

    Background/Aims: Growth Hormone (GH) dosage in childhood is adjusted for body size, but there is no consensus whether body weight (BW) or body surface area (BSA) should be used. We aimed at comparing the biological effect and cost-effectiveness of GH treatment dosed per m(2) BSA in comparison with d

  12. 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

  13. Durability of initial antiretroviral therapy in a resource-constrained setting and the potential need for zidovudine weight-based dosing.

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    Willig, James H; Echevarria, Juan; Westfall, Andrew O; Iglesias, David; Henostroza, German; Seas, Carlos; Mugavero, Michael J; Allison, Jeroan; Paz, Jorge; Hernandez, Fiorella; Tomatis, Cristina; Saag, Michael S; Gotuzzo, Eduardo

    2010-02-01

    Whereas access to antiretroviral therapy (ART) for HIV-infected individuals in the developing world is increasing, data on factors impacting initial regimen durability are lacking. Retrospective review patients starting initial ART at Instituto de Medicine Tropical (Lima, Peru) April 1, 2004 to December 30, 2007. Survival methods (Kaplan-Meier, Cox proportional hazard) assessed factors associated with regimen durability including an interaction term between nucleoside reverse transcriptase inhibitor backbone and time. Decreased initial regimen durability was observed with weight 70 kg. An increased risk of early toxicity-related discontinuation of AZT-containing regimens was observed for baseline weight 120 days) lowered hazards for regimen discontinuation. Weight <60 kg was associated with an increased risk of toxicity-related AZT discontinuation. As ART use expands globally, further study into maximally durable, least toxic regimens, and the role of weight-based AZT dosing is imperative.

  14. Fixed-dose combination for adults accessing antiretroviral therapy

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    SA HIV Clinicians Society

    2013-03-01

    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

  15. A proof that uniform dose gives the greatest TCP for fixed integral dose in the planning target volume

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    Webb, S.; Evans, P.M.; Swindell, W. (Institute of Cancer Research, Sutton (United Kingdom). Surrey Branch Royal Marsden Hospital, Sutton (United Kingdom)); Deasy, J.O. (Wisconsin Univ., Madison, WI (United States). Dept. of Medical Physics Wisconsin Univ., Madison, WI (United States). Dept. of Human Oncology)

    1994-11-01

    In this note it is shown that for a fixed integral dose to the planning target volume, the highest tumour control probability arises when the dose is spatially uniform. This 'uniform dose theorem' is proved both for (i) a specific TCP model based on Poisson/independent voxel statistics and (ii) any model for voxel control probability having a specific shape with respect to increasing dose. (author).

  16. A COMPARISON OF A BODYWEIGHT DOSE VERSUS A FIXED-DOSE OF NEBULIZED SALBUTAMOL IN ACUTE ASTHMA IN CHILDREN

    NARCIS (Netherlands)

    OBERKLAID, F; MELLIS, CM; LESOUEF, PN; GEELHOED, GC; MACCARRONE, AL

    1993-01-01

    Objective: To compare the efficacy of salbutamol as a fixed dose Ventolin Nebule (2.5 mg) and as variable dose respirator solution (0.1 mg/kg bodyweight). Design: Multicentre, randomised, double-blind, parallel group comparison. Setting: The Emergency Departments of the Royal Children's Hospital, Me

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

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    Lee, Jong Jin; Seok, Ju Won; Uh, Jae Sun [Seoul National University College of Medicine, Seoul (Korea, Republic of)] (and others)

    2005-07-01

    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.

  18. Treatment with fixed thyroxine doses in pregnant women with subclinical hypothyroidism.

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    Seoane Cruz, Inés; Penín Álvarez, Manuel; Luna Cano, Reyes; García-Mayor, Ricardo Víctor

    2012-05-01

    Hypothyroidism is usually treated with thyroxine doses on patient weight. In some cases, however, fixed doses have proved to useful to normalize TSH levels, which is especially important during pregnancy. Sixty-eight women diagnosed with subclinical hypothyroidism, autoimmune or not, during pregnancy were given a fixed dose of thyroxine 50 mcg/day. TSH measurements were performed to assess the need to change the dose, which was increased or decreased by 25 mcg/day when necessary. With a dose of 50 mcg/day of thyroxine, 42% of patients reached a TSH level less than 3 μU/mL, 79.4% reached a TSH level less than 4.5 μU/mL, and 20.6% had TSH levels higher than 4.5 μU/mL. Our data suggest that a fixed dose of thyroxine 50 mcg/day is inadequate in a significant proportion of pregnancy-diagnosed hypothyroidism regardless of whether the reference of TSH level used is 4.5 or 3 μU/mL. S starting dose of 75 mcg/day is probably more adequate, but studies are needed to evaluate the possibility of overtreatment with such dose. Copyright © 2011 SEEN. Published by Elsevier Espana. All rights reserved.

  19. Fixed-dose lercanidipine and enalapril in field practice: a meta-analysis.

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    Rizzoni, Damiano

    2016-10-01

    This meta-analysis evaluates the efficacy and safety of lercanidipine/enalapril fixed-dose combination in patients with mild to moderate essential hypertension. Four observational studies on patients with sitting diastolic blood pressure (SDBP) between 95 and 109 mmHg, treated with lercanidipine/enalapril fixed-dose combination, were analyzed. The Random-Effect Model was used to limit heterogeneity across the studies. Weights were applied to determine the influence of each study on the combined results. The efficacy outcome measure was the reduction from baseline to endpoint in systolic and diastolic blood pressure (SBP and DBP, respectively). The incidence of treatment-emergent adverse events (TEAEs) was also investigated. The total number of patients analyzed for efficacy and safety was 9565. No differences between study groups in demographics characteristics were observed. Mean blood pressure in the pooled population of the four studies was 162/94 mmHg at baseline. Overall, the lercanidipine/enalapril fixed-dose combination reduced SBP by 26 mmHg (95% CI, 23-29), and DBP by 13 mmHg (12-15), p < 0.05 for both. No safety concerns were reported. This meta-analysis supports the use of the lercanidipine/enalapril fixed-dose combination for the treatment of mild-to-moderate hypertension.

  20. A cost-minimization analysis of combination therapy in hypertension: fixed-dose vs extemporary combinations

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    Marco Bellone

    2013-12-01

    Full Text Available BACKGROUND: Cardiovascular disease management and prevention represent the leading cost driver in Italian healthcare expenditure. In order to reach the target blood pressure, a large majority of patients require simultaneous administration of multiple antihypertensive agents.OBJECTIVE: To assess the economic impact of the use of fixed dose combinations of antihypertensive agents, compared to the extemporary combination of the same principles.METHODS: A cost minimization analysis was conducted to determine the pharmaceutical daily cost of five fixed dose combinations (olmesartan 20 mg + amlodipine 5 mg, perindopril 5 mg + amlodipine 5 mg, enalapril 20 mg + lercanidipine 10 mg, felodipine 5 mg + ramipril 5 mg, and delapril 30 mg + manidipine 10 mg compared with extemporary combination of the same principles in the perspective of the Italian NHS. Daily acquisition costs are estimated based on current Italian prices and tariffs.RESULTS: In three cases the use of fixed‑dose combination instead of extemporary combination induces a lower daily cost. Fixed combination treatment with delapril 30 mg + manidipine 10 mg induces greater cost savings for the National Health System (95,47 €/pts/year, as compared to free drugs combination therapy.CONCLUSIONS: Compared with free drug combinations, fixed‑dose combinations of antihypertensive agents are associated with lower daily National Health Service acquisition costs.http://dx.doi.org/10.7175/fe.v14i4.886

  1. Is the fixed-dose combination of telmisartan and hydrochlorothiazide a good approach to treat hypertension?

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    Marc P Maillard

    2007-07-01

    Full Text Available Marc P Maillard, Michel BurnierService of Nephrology, Department of Internal Medicine, Lausanne University Hospital, SwitzerlandAbstract: Blockade of the renin-angiotensin system with selective AT1 receptor antagonists is recognized as an effective mean to lower blood pressure in hypertensive patients. Among the class of AT1 receptor antagonists, telmisartan offers the advantage of a very long half-life. This enables blood pressure control over 24 hours using once-daily administration. The combination of telmisartan with hydrochlorothiazide is a logical step because numerous previous studies have demonstrated that sodium depletion enhances the antihypertensive efficacy of drugs interfering with the activity of the renin-angiotensin system (RAS. In accordance with past experience using similar compounds blocking the RAS, several controlled studies have now demonstrated that the fixed-dose combination of telmisartan/hydrochlorothiazide is superior in lowering blood pressure than either telmisartan or hydrochlorothiazide alone. Of clinical interest also is the observation that the excellent clinical tolerance of the angiotensin II receptor antagonist is not affected by the association of the low-dose thiazide. Thus telmisartan/hydrochlorothiazide is an effective and well-tolerated antihypertensive combination. Finally, the development of fixed-dose combinations should improve drug adherence because of the one-pill-a-day regimen.Keywords: telmisartan, hydrochlorothiazide, fixed-dose combinations, antihypertensive agent, safety, compliance

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

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    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.

  3. [Pharmacodynamics and pharmacokinetics of domestic fixed-dose combination of antituberculosis drugs].

    Science.gov (United States)

    Zhao, Weijie; Li, Huiwen; Duan, Lianshan; Liang, Guifang; Zhang, Tongqun; Lu, Yu

    2002-06-01

    OBJECTIVE To study the pharmacodynamics and pharmacokinetics of domestic fixed-dose of antituberculosis drugs and to evaluate its quality and activity against Mycobacterium tuberculosis both in vitro and in vivo. METHODS The MIC was determined by the tube doubling dilution method, and the effect of the drugs was assessed by half survival time of the mice. A single oral dose of domestic and imported fixed-dose combination of antituberculosis drugs was given to healthy volunteers, and the drug concentration in serum was determined by HPLC. The pharmacokinetic parameters and the relative bioavailability were calculated. RESULTS The MIC of each composition in the compound (INH, RFP, PZA) against Mycobacterium tuberculosis was lower than that of each composition used by single-dose. In a murine tuberculosis model, the antituberculosis activity of this compound drug was superior to that of each agent used alone with the same dose. No significant difference was found as compared to the imported drug, Refater; The major pharmacokinetic parameters of the domestic and the imported drugs, t (1/2), C (max), AUC, and t(max), were not significantly different. Statistical analysis showed the two formulations were bioequivalent. CONCLUSION The three compositions in the combination had synergistic effect, and the domestic and the imported drugs were bioequivalent.

  4. Targeting postprandial hyperglycaemia in patients with recently diagnosed type 2 diabetes with a fixed, weight-based dose of insulin Aspart

    DEFF Research Database (Denmark)

    Gredal, C.; Rosenfalck, A.M.; Dejgaard, A.

    2008-01-01

    -blind, double-dummy design, 20 patients underwent three 3-day periods with injection of IAsp 0.06 IU/kg BW or placebo 30 min before main meals. The effect on blood glucose fluctuations was evaluated using a continuous glucose monitoring system. Efficacy endpoints were time with glucose values above 8 mmol...... areas above 8 mmol/L were 0.6+/-0.2 mmol/lxh and 1.2+/-0.2 mmol/lxh for IAsp and placebo, respectively (pregistration below 4 mmol/L. Patients with HbA(1c) below 7.4 % obtained the greatest...

  5. A fixed-dose ketamine protocol for adolescent sedations in a pediatric emergency department.

    Science.gov (United States)

    Street, Megan H; Gerard, James M

    2014-09-01

    To assess provider and patient satisfaction with a fixed-dose ketamine protocol for procedural sedation of adolescent subjects. We further compared data for normal weight (body mass index [BMI] ≤ 25 kg/m(2)) vs overweight/obese subjects (BMI >25 kg/m(2)). Prospective, observational cohort study of adolescent patients undergoing procedural sedation in a pediatric emergency department. Adequate sedation was defined as a Ramsay Sedation Score (RSS) ≥ 5. Subjects received an initial 50 mg intravenous ketamine dose followed by 25 mg intravenous doses to maintain an RSS ≥ 5. The sedating physician, procedural physician, and sedating nurse independently rated the sedations on a 100 mm visual analog scale (0 = "very unsatisfied", 100 = "very satisfied"). Subjects and their guardians were contacted 12-24 hours postsedation. Forty-three subjects (26 normal weight, 17 overweight/obese), aged 12-17 years, were enrolled in the study. An RSS ≥ 5 was observed in 35 (81.4%) of the subjects following the initial 50 mg ketamine dose and in the remaining 8 subjects following the first additional 25 mg dose. The median combined provider satisfaction score for the sedations was 92.7 (IQR 83.7-95.0) and was similar for the normal weight and overweight/obese groups (93.1 [IQR 84.6-95.9] vs 89.7 [IQR 83.7-93.5], respectively, P = .27). Subjects and guardians in both groups reported high rates of satisfaction. The fixed-dose ketamine protocol resulted in an adequate level of sedation and high provider/patient satisfaction for the majority of patients regardless of weight or BMI status. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Telmisartan/Hydrochlorothiazide: a review of its use as fixed-dose combinations in essential hypertension.

    Science.gov (United States)

    Plosker, Greg L; White, William B

    2008-01-01

    Fixed-dose combinations of telmisartan and hydrochlorothiazide (HCTZ) [Micardis Plus, Micardis HCT, PritorPlus] are available in many countries for the treatment of patients with essential hypertension. Combining the angiotensin II receptor antagonist (angiotensin II receptor blocker [ARB]) telmisartan with the thiazide diuretic HCTZ provides antihypertensive therapy with complementary mechanisms of action. In the US and EU, telmisartan/HCTZ is approved for patients whose hypertension is not adequately controlled with telmisartan monotherapy; US labelling for the fixed-dose combination also includes inadequate control of blood pressure (BP) with HCTZ monotherapy.The antihypertensive efficacy of once-daily telmisartan/HCTZ has been demonstrated in several large, randomized trials in patients with stages 1 and 2 hypertension. The addition of HCTZ to telmisartan achieved significant reductions in BP in nonresponders to telmisartan monotherapy, and the antihypertensive efficacy of telmisartan/HCTZ was similar to or significantly greater than that of various comparator agents. Moreover, in studies that used ambulatory BP monitoring, telmisartan/HCTZ provided consistent 24-hour BP reductions throughout morning, daytime and night-time periods. The BP-lowering efficacy over the entire 24-hour dose administration interval is consistent with the pharmacokinetic profile of telmisartan, which has the longest elimination half-life among currently available ARBs and a unique chemical structure. Adverse events with telmisartan/HCTZ in clinical trials were typically mild and transient, and no unexpected events occurred that had not been previously reported with either telmisartan or HCTZ. Extensive tolerability data are available for telmisartan, in particular from the ONTARGET study, the largest clinical outcomes trial with an ARB. As such, fixed-dose combinations of telmisartan/HCTZ provide an effective, rational and generally well tolerated treatment option for the management

  7. Overcoming clinical inertia to achieve blood pressure goals: the role of fixed-dose combination therapy.

    Science.gov (United States)

    Basile, Jan; Neutel, Joel

    2010-04-01

    The treatment of hypertension should cause blood pressure (BP) changes that reduce the long-term risks of cardiovascular morbidity and mortality. There are considerable clinical benefits to be gained by promptly treating patients to recognized BP goals, particularly for those at high risk. This may be achieved by the use of combination therapy as first-line treatment. However, despite widely acknowledged therapeutic guidelines, there are significant gaps between current treatment recommendations and their implementation in clinical practice. One important explanation for inadequate treatment and subsequent poor BP control is clinical inertia. Undertreatment and clinical inertia may sometimes be mistaken for treatment-resistant hypertension, as is often the case in specific patient populations whose disease is often considered a challenge to treat because of a greater risk of cardiovascular complications (e.g. Blacks, obese patients, and those with diabetes). The availability of fixed-dose drug combinations may address some of the common misconceptions thought to promote clinical inertia. Few studies have specifically focused on subpopulations with difficult-to-treat hypertension that is uncontrolled on monotherapies. One example is an ongoing 20-week, multicenter, prospective, blinded endpoint, dose-titration, treat-to-goal study evaluating the efficacy and safety of initial fixed-dose combination therapy with amlodipine/olmesartan medoxomil, and further up-titration with hydrochlorothiazide, in patients with hypertension who are uncontrolled on antihypertensive monotherapy. This study may demonstrate the benefits of treating patients with hypertension to goal using initial fixed-dose combination therapy, even in patients considered to be at a higher risk of cardiovascular complications.

  8. The fixed-point iteration method for IMRT optimization with truncated dose deposition coefficient matrix

    CERN Document Server

    Tian, Zhen; Jia, Xun; Jiang, Steve B

    2013-01-01

    In the treatment plan optimization for intensity modulated radiation therapy (IMRT), dose-deposition coefficient (DDC) matrix is often pre-computed to parameterize the dose contribution to each voxel in the volume of interest from each beamlet of unit intensity. However, due to the limitation of computer memory and the requirement on computational efficiency, in practice matrix elements of small values are usually truncated, which inevitably compromises the quality of the resulting plan. A fixed-point iteration scheme has been applied in IMRT optimization to solve this problem, which has been reported to be effective and efficient based on the observations of the numerical experiments. In this paper, we aim to point out the mathematics behind this scheme and to answer the following three questions: 1) whether the fixed-point iteration algorithm converges or not? 2) when it converges, whether the fixed point solution is same as the original solution obtained with the complete DDC matrix? 3) if not the same, wh...

  9. 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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

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

    Directory of Open Access Journals (Sweden)

    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

  11. Fixed-dose combination vs monotherapy in hypertension: a meta-analysis evaluation.

    Science.gov (United States)

    Hilleman, D E; Ryschon, K L; Mohiuddin, S M; Wurdeman, R L

    1999-07-01

    Fixed-dose combination antihypertensive therapy has received interest since the publication of the JNC-VI report. Relatively few head-to-head comparative studies between fixed-dose combinations and first-line monotherapies for hypertension have been published. The objective of this study was to conduct a meta-analysis of various first-line monotherapies and the fixed-dose combination of amlodipine/benazepril. The results of the meta-analysis were used to compare the efficacy and safety of the first-line monotherapies with amlodipine/benazepril. The meta-analysis included 82 studies that included 110 treatment groups (cohorts). The study compared nine different monotherapies and one combination therapy (amlodipine/benazepril). Of the 82 studies, 22 were placebo-controlled and 60 were active treatment controlled. The mean absolute decrease in supine diastolic blood pressure (BP) ranged from 9.7 to 13.3 mm Hg with verapamil showing the greatest effect and captopril the least (13.3 +/- 3.0 mm Hg; 9.7 +/- 2.9 mm Hg, respectively). When studies were weighted by sample size, atenolol, verapamil, lisinopril and amlodipine/benazepril showed the greatest BP effect. When studies were weighted by variance, amlodipine/benazepril and atenolol showed the greatest BP effect. The percentage of patients controlled on therapy ranged from 54% to 79%. Lisinopril and amlodipine/benazepril showed the greatest percent controlled. The overall incidence of adverse effects ranged from 12.1% to 41.8% with lisinopril having the lowest and nifedipine having the highest incidence. The overall incidence of adverse effects resulting in drug discontinuance ranged from 1.3% to 10.7%, with amlodipine/benazepril having the lowest and nifedipine having the highest incidence. The results of the meta-analysis indicate that amlodipine/benazepril produces above average reductions in BP with a lower than average incidence of overall side effects and the lowest incidence of adverse effects resulting in drug

  12. Ledipasvir/sofosbuvir fixed-dose combination for treatment of hepatitis C virus genotype 4 infection.

    Science.gov (United States)

    Nehra, V; Tan, E M; Rizza, S A; Temesgen, Z

    2016-02-01

    Hepatitis C virus (HCV) genotype 4 accounts for 8-13% of all chronic HCV infections worldwide. Patients with HCV genotype 4 have been reported to have poor treatment responses to PEGylated interferon and ribavirin regimens. Recently a single tablet, fixed-dose combination of sofosbuvir, an RNA-directed RNA polymerase (NS5B) inhibitor, and ledipasvir, a nonstructural protein 5A (NS5A) inhibitor, has been approved for treatment of chronic HCV infection. Two studies using the fixed-dose combination in chronic HCV genotype 4 for 12 weeks reported sustained virologic response rates at 12 weeks (SVR12) of 93-95%. Data also support the use of ledipasvir/sofosbuvir in chronic HCV genotype 4 and HIV co-infection. Administered as a single once-daily oral regimen, this ribavirin- and interferon-free regimen is well tolerated, with low potential for adverse effects and represents a significant advancement in the treatment of chronic HCV genotype 4 infection.

  13. A Phase I-II dose escalation study of fixed-dose rate gemcitabine, oxaliplatin and capecitabine every two weeks in advanced cholangiocarcinomas

    DEFF Research Database (Denmark)

    Lassen, Ulrik; Jensen, Lars Henrik; Sorensen, Morten;

    2011-01-01

    Gemcitabine based regimens have been widely used in patients with advanced cholangiocarcinoma (CC), but no standard therapy exists. In this study we aimed to find the maximally tolerated dose (MTD) of a two-week schedule of fixed dose rate (FDR) gemcitabine (G), oxaliplatin (O) and capecitabine (...

  14. A stable fixed-dose combination tablet of pseudoephedrine and KOB extracts for the extended release.

    Science.gov (United States)

    Hwang, C-J; Park, M-H; Jung, H-W; Park, Y-K; Kim, Y-H; Kang, J-S; Cho, C-W

    2013-11-01

    Allergic rhinitis (AR) is characterized by inflammation of the nasal mucosa with hypersensitivity resulting from seasonal or perennial responses to specific environmental allergens and by symptoms like nasal rubbing, sneezing, rhinorrhea, lacrimation, nasal congestion and obstruction, and less frequently cough. KOB extracts, which is a polyherbal medicine consisting of 5 different herbs (Atractylodes macrocephala, Astragalus membranaceus, Saposhnikovia divaricata, Ostericum koreanum and Scutellaria baicalensis) had commonly been used for the treatment of various allergic diseases showed an anti-allergic effect by modulating mast cell-mediated allergic responses in allergic rhinitis, recently. On the other hand, pseudoephedrine is a sympathomimetic amine commonly used to relieve congestion in patients with allergic rhinitis and common colds. Considering the KOB's therapeutic mechanism, the combination with pseudoephedrine would be suitable for allergic rhinitis. This study is to obtain an effective extended release formulation using pseudoephedrine and KOB extracts to reduce side effects of drug due to repeated dosing and improve the compliance of patients for treatment of rhinitis and nasal decongestion. So, the fixed-dose combination tablet of pseudoephedrine and KOB extracts was prepared by direct compression and characterized by drug content, flowing characteristics and dissolution test. The drug content of baicalin of KOB extracts was within the range of 95-105% except for T1 formulation. The hardness and friability values of all formulations ranged from 9 to 13 kp and less than 1%, respectively. Taken together, T4 or T8 could be a stable fixed-dose combination tablet for extended release of pseudoephedrine and KOB extracts for nasal rhinitis.

  15. Capillary electrophoresis for the assay of fixed-dose combination tablets of artesunate and amodiaquine

    Directory of Open Access Journals (Sweden)

    Amin N’Cho

    2012-05-01

    Full Text Available Abstract Background Quality control of drugs in formulations is still a major challenge in developing countries. For the quality control of artesunate and amodiaquine tablets in fixed-dose combination, only liquid chromatographic methods have been proposed in the literature. There are no capillary electrophoretic methods reported for the determination of these active substances, although this technique presents several advantages over liquid chromatography (long lifetime, low price of the capillary, low volumes of electrolyte consumption in addition to simplicity. In this paper, a reliable capillary electrophoresis method has been developed and validated for the quality control of these drugs in commercial fixed-dose combination tablets. Methods Artesunate and amodiaquine hydrochloride in bilayer tablets were determined by micellar electrokinetic capillary chromatography (MEKC. Analytes were extracted from tablets by sonication with a solvent mixture phosphate buffer pH 7.0-acetonitrile containing benzoic acid as internal standard. Separation was carried out on Beckman capillary electrophoresis system equipped with fused silica capillary, 30 cm long (20 cm to detector × 50 μm internal diameter, using a 25 mM borate buffer pH 9.2 containing 30 mM sodium dodecyl sulfate as background electrolyte, a 500 V cm−1 electric field and a detection wavelength of 214 nm. Results Artesunate, amodiaquine and benzoic acid were separated in 6 min. The method was found to be reliable with respect to specificity,linearity of the calibration line (r2 > 0.995, recovery from synthetic tablets (in the range 98–102%, repeatability (RSD 2–3%, n = 7 analytical procedures. Application to four batches of commercial formulations with different dosages gave content in good agreement with the declared content. Conclusion The MEKC method proposed is reliable for the determination of artesunate and amodiaquine hydrochloride in fixed-dose

  16. Artesunate-amodiaquine fixed dose combination for the treatment of Plasmodium falciparum malaria in India

    Directory of Open Access Journals (Sweden)

    Anvikar Anupkumar R

    2012-03-01

    Full Text Available Abstract Background Artemisinin-based combination therapy (ACT has been recommended for the treatment of falciparum malaria by the World Health Organization. Though India has already switched to ACT for treating falciparum malaria, there is need to have multiple options of alternative forms of ACT. A randomized trial was conducted to assess the safety and efficacy of the fixed dose combination of artesunate-amodiaquine (ASAQ and amodiaquine (AQ for the treatment of uncomplicated falciparum malaria for the first time in India. The study sites are located in malaria-endemic, chloroquine-resistant areas. Methods This was an open label, randomized trial conducted at two sites in India from January 2007 to January 2008. Patients between six months and 60 years of age having Plasmodium falciparum mono-infection were randomly allocated to ASAQ and AQ arms. The primary endpoint was 28-day PCR-corrected parasitological cure rate. Results Three hundred patients were enrolled at two participating centres, Ranchi, Jharkhand and Rourkela, Odisha. Two patients in AQ arm had early treatment failure while there was no early treatment failure in ASAQ arm. Late treatment failures were seen in 13 and 12 patients in ASAQ and AQ arms, respectively. The PCR-corrected cure rates in intent-to-treat population were 97.51% (94.6-99.1% in ASAQ and 88.65% (81.3-93.9% in AQ arms. In per-protocol population, they were 97.47% (94.2-99.2% and 88.30% (80-94% in ASAQ and AQ arms respectively. Seven serious adverse events (SAEs were reported in five patients, of which two were reported as related to the treatment. All SAEs resolved without sequel. Conclusion The fixed dose combination of ASAQ was found to be efficacious and safe treatment for P. falciparum malaria. Amodiaquine also showed acceptable efficacy, making it a suitable partner of artesunate. The combination could prove to be a viable option in case India opts for fixed dose combination ACT. Clinical trial registry

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

    Directory of Open Access Journals (Sweden)

    Pergolizzi Jr JV

    2012-08-01

    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 minimal toxicity.Keywords: NSAIDs, opioids, combination analgesics, moderate pain, severe pain, analgesics, tramadol/paracetamol

  18. Ledipasvir/sofosbuvir: the fixed dose combination in the new era of treatment for HCV

    Directory of Open Access Journals (Sweden)

    Alessia Ciancio

    2015-07-01

    Full Text Available Interferon-based treatment is not suitable for many patients with hepatitis C virus (HCV infection because of contraindications, other reasons for ineligibility and side-effects. The fixed dosed combination ledipasvir/sofosbuvir (LDV / SOF is the first approved regimen that doesn’t require administration with interferon or ribavirin. LDV / SOF is also the first single-pill approved for the treatment of chronic HCV genotype 1 in both treatment-naïve and treatment-experienced patients. The results of the phase III studies demonstrate the combination has been very well tolerated and SVR rates consistently above 90%. Objective of this review is to present clinical evidence of efficacy and safety of the combination LDV / SOF in different subgroups of patients with HCV.

  19. An evaluation of knowledge, attitude and practices about prescribing fixed dose combinations among resident doctors

    Directory of Open Access Journals (Sweden)

    Nimit Goswami

    2013-01-01

    Full Text Available Background: Fixed Dose Combinations (FDCs improve patient compliance and decrease pill burden. However, irrational prescribing of FDCs is a major health concern. As resident doctors are primarily involved in patient management at tertiary care hospitals, knowledge about prescribing FDCs is of paramount importance. Objective: To evaluate knowledge, attitude and practice, regarding use of FDCs by resident doctors at a tertiary care teaching hospital. Materials and Methods: The study was carried out among resident doctors working at Civil Hospital, Ahmedabad, a tertiary care teaching hospital. One hundred resident doctors from the departments of medicine, obstetrics and gynaecology, surgery, paediatrics, skin and psychiatry, who gave their informed consent, were enrolled. A prevalidated questionnaire regarding knowledge, attitude and prescribing practice of fixed dose combinations was filled up. Data was analyzed with suitable statistical tests. Results: Out of the 100 residents recruited for the study, 34, 33 and 33 residents were selected from the 1 st , 2 nd and 3 rd year respectively. The resident doctors were not aware about all of the advantages and disadvantages of FDCs. On an average, only 31% of the residents (lowest 16% among 1 st year residents had knowledge about the Essential Medicine List (EML. Knowledge about rationality of given FDCs was lacking in 81% of the residents. Only 47% could name a single banned FDC in India. Common sources of information about FDCs were medical representatives, colleagues/peers, the Monthly Index of Medical Specialities (MIMS and Continuous Medical Education (CMEs. A majority of residents (96% agreed that FDCs should be allowed to be marketed. The residents opined that most commonly prescribed FDCs were of antimicrobial drugs, amongst which amoxicillin + clavulanic acid was the most frequent. Conclusion: There is need to improve knowledge about rationality, EML, usage and banned FDCs in post graduate

  20. Assessing the risk of birth defects associated with exposure to fixed-dose combined antituberculous agents during pregnancy in rats.

    Science.gov (United States)

    Awodele, O; Patrick, E B; Oluwatoyin Agbaje, Esther; Oremosu, A A; Gbotolorun, S C

    2012-01-01

    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 (P ≤ 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 (P ≤ 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 significantly

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

    Directory of Open Access Journals (Sweden)

    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

  2. SSRIs and ejaculation: a double-blind, randomized, fixed-dose study with paroxetine and citalopram.

    Science.gov (United States)

    Waldinger, M D; Zwinderman, A H; Olivier, B

    2001-12-01

    Selective serotonin reuptake inhibitors (SSRIs) are known to induce delayed orgasm and ejaculation. However, different SSRIs may differentially delay ejaculation. A double-blind, fixed-dose study in healthy men with lifelong rapid ejaculation was performed to evaluate potential differences between clinically relevant doses of two selective serotonin reuptake inhibitors, paroxetine and citalopram, in their effects on ejaculation. Thirty men with an intravaginal ejaculation latency time (IELT) less than 1 minute were randomly assigned to receive paroxetine (20 mg/day) and citalopram (20 mg/day) for 5 weeks, after taking half the dosage in the first week. During the 1-month baseline and 6-week treatment period, IELTs were measured at home by using a stopwatch procedure. The trial was completed by 23 men. Analysis of variance revealed a between-group difference in the evolution of IELT delay over time (p = 0.0004); the IELT after paroxetine and citalopram gradually increased from 18 and 21 seconds to approximately 170 and 44 seconds, respectively. Paroxetine 20 mg/day exerted a strong delay (8.9-fold increase), whereas citalopram 20 mg/day mildly delayed ejaculation (1.8-fold increase). These results indicate that paroxetine leads to a significant delay in orgasm and ejaculation, whereas citalopram seems to have less of an effect on it.

  3. Effectiveness and tolerability of a fixed-dose combination of olmesartan and amlodipine in clinical practice

    Directory of Open Access Journals (Sweden)

    Peter Bramlage

    2010-08-01

    Full Text Available Peter Bramlage1, Wolf-Peter Wolf2, Thomas Stuhr2, Eva-Maria Fronk3, Wolfhard Erdlenbruch2, Reinhard Ketelhut4, Roland E Schmieder51Institute for Cardiovascular Pharmacology and Epidemiology, Mahlow; 2Daiichi Sankyo Deutschland GmbH, Munich, Germany; 3Daiichi Sankyo Europe GmbH, Munich, Germany; 4Department of Sports Medicine, Universitätsklinikum Berlin; 5Department of Nephrology and Hypertension, University Hospital of Erlangen, GermanyObjectives: To assess the efficacy and tolerability of a fixed-dose combination of olmesartan and amlodipine in an unselected population of patients in primary care and to compare the results with recent randomized controlled trial evidence.Methods: A multicenter, noninterventional, noncontrolled observational study with 8241 hypertensive patients seen by 2187 physicians in daily practice. Blood pressure (BP reduction, comorbid disease, pharmacotherapy, and tolerability were documented over a 12–18-week observational period.Results: Patients had a mean age of 62.8 ± 11.8 years (48.1% female, and 74.8% had at least one comorbid risk factor or condition. In total, 51.3% received olmesartan-amlodipine 20/5 mg, 30.6% received 40/5 mg, and 17.9% received 40/10 mg at baseline, mostly because of lack of efficacy on prior antihypertensive therapy (73.8%. BP at baseline was 161.8 ± 16.6/93.6 ± 10.2 mmHg (39.8% had Grade 2 hypertension, and the observed BP reduction was -29.0 ± 17.1/-13.5 ± 10.9 mmHg (P < 0.0001, with a significant correlation between BP at baseline and BP reduction (Spearman’s Rho -0.811 for systolic BP and -0.759 for diastolic BP. BP reduction appeared to be dependent on dose and prior antihypertensive therapy, but not on age, gender, body mass index, duration of hypertension, or the presence of diabetes. At the final visit, 69.4% (4.3% at baseline were controlled (<140/90 mmHg. Adverse drug reactions were observed in 2.76% of the study population; 94.25% of these adverse drug reactions were

  4. 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

  5. Fixed-dose combinations in type 2 diabetes – role of the canagliflozin metformin combination

    Directory of Open Access Journals (Sweden)

    Fleming JW

    2015-06-01

    Full Text Available Joshua W Fleming, Laurie W Fleming, Courtney S Davis Department of Pharmacy Practice, The University of Mississippi School of Pharmacy, Jackson, MS, USA Abstract: Canagliflozin–metformin is one of the newest combination therapies available for the treatment of type 2 diabetes mellitus (T2DM. Canagliflozin is an inhibitor of the sodium–glucose co-transporter 2 which causes an increase in the urinary excretion of glucose. In the present article, we review the safety and efficacy of canagliflozin and metformin from data obtained from Phase III metformin add-on therapy clinical trials as there are no studies to date that specifically evaluate the combination of metformin and canagliflozin. Trials included in this review were dual-therapy trials of subjects who were already taking background metformin and were assigned to receive canagliflozin, glimepiride, or sitagliptin. The addition of canagliflozin to metformin resulted in a decrease in HbA1c of 0.73%–0.93%. Canagliflozin 100 mg was considered to be non-inferior to glimepiride and sitagliptin 100 mg with the canagliflozin 300 mg dose being statistically superior to sitagliptin and glimepiride. Other advantages of the use of canagliflozin are reduction in weight (3.3–4.0 kg and systolic blood pressure (3.3–4.7 mmHg. The primary disadvantages are potential genital mycotic infections, hypotension, and gastrointestinal side effects from metformin. All things considered, this combination appears to be safe and effective in clinical trials and represents a promising option for the treatment of T2DM. Keywords: type 2 diabetes, fixed-dose combination (FDC, canagliflozin metformin 

  6. 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.

  7. 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.

  8. Management of dyslipidemia and hyperglycemia with a fixed-dose combination of sitagliptin and simvastatin.

    Science.gov (United States)

    Steinberg, Helmut; Anderson, Matt S; Musliner, Thomas; Hanson, Mary E; Engel, Samuel S

    2013-01-01

    The risk of death due to heart disease and stroke is up to four times higher in individuals with diabetes compared to individuals without diabetes. Most guidelines that address treatment of dyslipidemia in patients with diabetes consider diabetes a cardiovascular disease (CVD) "risk equivalent" and recommend intensive treatment of dyslipidemia for the purpose of CVD prevention. Statins (3-hydroxy 3-methylglutaryl coenzyme A reductase [HMG-CoA reductase] inhibitors) are first-line agents in achieving lipid goals as an adjunct to diet and exercise and should be used in most patients. In addition to lipid management and blood pressure control, glycemic control is a basic component in the management of diabetes. Glycemic control is achieved by combining diabetes self-management education, diet and exercise, and, where required, antihyperglycemic agents (OHAs). Persistence and adherence to therapy are critical in achieving recommended treatment goals. However, overall compliance with concomitantly prescribed OHAs and statins is low in patients with type 2 diabetes. Fixed-dose combination (FDC) therapies have been shown to improve adherence by reducing pill burden, the complexity of treatment regimen, and, potentially, cost. Based on the available evidence regarding the pharmacokinetics and the efficacy and safety profiles of each component drug, the sitagliptin/simvastatin FDC may provide a rational and well-tolerated approach to achieving better adherence to multiple-drug therapy and improved lipid lowering and glycemic control, with consequent reduction in cardiovascular risk, diabetic microvascular disease, and mortality in diabetic patients for whom treatment with both compounds is appropriate.

  9. Steepness of the radiation dose-response curve for dose-per-fraction escalation keeping the number of fractions fixed.

    Science.gov (United States)

    Bentzen, Søren M

    2005-01-01

    Clinically, there is growing interest in strategies for intensifying radiation therapy by escalating the dose per fraction. This paper considers the steepness of the dose-response curve in this case. The steepness of a radiation dose-response curve is most conveniently quantified by the normalized dose-response gradient, gamma. Under the assumption of a linear-quadratic dose-effect model, a simple analytical relationship is derived between the gamma-value for a dose-response curve generated by varying the total dose while keeping the number of fractions constant, i.e. escalating the dose per fraction, and the gamma-value for a dose-response curve generated by varying the total dose while keeping the dose per fraction constant. This formulation is compared with clinical dose-response data from the literature and shown to be in good agreement with the observations. Some implications of this formulation for non-uniform dose distributions delivered using 3D conformal radiotherapy or intensity modulated radiotherapy (IMRT) are briefly discussed.

  10. 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...

  11. Dose-Response Analysis of RNA-Seq Profiles in Archival Formalin-fixed paraffin-embedded (FFPE) Samples

    Science.gov (United States)

    Formalin-fixed paraffin-embedded (FFPE) samples provide a vast untapped resource for chemical safety and translational science. To date, genomic profiling of FFPE samples has been limited by poor RNA quality and inconsistent results with limited utility in dose-response assessmen...

  12. 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...

  13. Use of antibacterial fixed-dose combinations in the private sector in eight Latin American Countries between 1999 and 2009

    NARCIS (Netherlands)

    Wirtz, Veronika J.; Mol, Peter G. M.; Verdijk, Jonneke; Stichele, Robert H. Vander; Taxis, Katja

    2013-01-01

    OBJECTIVE: To assesses the safety and rationale of antibacterial fixed-dose combinations in the private sector in Latin America and determine the extent of their use. METHODS: Analysis of FDCs was based on retail sales data for eight Latin American countries (Argentina, Brazil, Chile, Colombia, Mexi

  14. Critical Analysis of Cardiovascular and Central Nervous System Fixed Dose Combinations Available in Indian Market

    Science.gov (United States)

    Prajapati, Krunal; Shah, Samidh

    2016-01-01

    Introduction Fixed Dose Combinations (FDCs) are being increasingly used to improve compliance and achieve greater benefits of the two or more active ingredients given together than the corresponding individual drug components given separately. Aim To analyse the rationality of Cardiovascular (CV) and Central Nervous System (CNS) FDCs available in Indian market. Materials and Methods CVS and CNS FDCs, enlisted in Indian Drug Review, 2014, were analysed by a pretested validated eight point criteria tool. Each FDC was assessed for number of active pharmacological ingredients, approval by regulatory authority, listing in WHO Essential Medicine List. While efficacy, safety, pharmacokinetic, pharmacodynamic interactions and advantages of each FDC were analysed by literature search. The total score of the tool was 12 and score ≥7 was considered rational. FDCs were divided in four groups as per rationality and DCGI approval. ANOVA was used for statistical analysis and p45 belonged to CNS group and 40 had documented evidence of efficacy and safety. Majority of FDCs showed advantage of being convenient by reducing pill count and only 32 showed reducing adverse drug reactions. Out of 107 CV FDCs, 46 were rational and 61 were irrational with a mean rationality score of 6.72±2.82 (CI– 95 %, 3.90 - 9.54). While out of 45 CNS FDCs, 8 were rational and 37 were irrational with a mean rationality score of 6.22±2.08 (CI – 95 %, 4.14 - 8.30). A significant difference in mean rationality score of group A (DCGI approved + rational) was observed as compared to group B (DCGI approved + irrational) and group C (DCGI unapproved + rational) as compared to group D (DCGI unapproved + irrational) (p<0.05). Conclusion The absence of watertight pre-requisite, critical analysis of the scientific validity of the formulations and ‘convenience’ category has resulted into proliferation of irrational FDCs. This calls for strict regulatory approval process to avoid miserable FDC scenario in

  15. Management of dyslipidemia and hyperglycemia with a fixed-dose combination of sitagliptin and simvastatin

    Directory of Open Access Journals (Sweden)

    Steinberg H

    2013-05-01

    Full Text Available Helmut Steinberg, Matt S Anderson, Thomas Musliner, Mary E Hanson, Samuel S EngelMerck Sharp & Dohme Corp., Whitehouse Station, NJ, USAAbstract: The risk of death due to heart disease and stroke is up to four times higher in individuals with diabetes compared to individuals without diabetes. Most guidelines that address treatment of dyslipidemia in patients with diabetes consider diabetes a cardiovascular disease (CVD "risk equivalent" and recommend intensive treatment of dyslipidemia for the purpose of CVD prevention. Statins (3-hydroxy 3-methylglutaryl coenzyme A reductase [HMG-CoA reductase] inhibitors are first-line agents in achieving lipid goals as an adjunct to diet and exercise and should be used in most patients. In addition to lipid management and blood pressure control, glycemic control is a basic component in the management of diabetes. Glycemic control is achieved by combining diabetes self-management education, diet and exercise, and, where required, antihyperglycemic agents (OHAs. Persistence and adherence to therapy are critical in achieving recommended treatment goals. However, overall compliance with concomitantly prescribed OHAs and statins is low in patients with type 2 diabetes. Fixed-dose combination (FDC therapies have been shown to improve adherence by reducing pill burden, the complexity of treatment regimen, and, potentially, cost. Based on the available evidence regarding the pharmacokinetics and the efficacy and safety profiles of each component drug, the sitagliptin/simvastatin FDC may provide a rational and well-tolerated approach to achieving better adherence to multiple-drug therapy and improved lipid lowering and glycemic control, with consequent reduction in cardiovascular risk, diabetic microvascular disease, and mortality in diabetic patients for whom treatment with both compounds is appropriate.Keywords: statin, oral antihyperglycemic agent, diabetes, adherence, cardiovascular disease, microvascular disease

  16. Co-extrusion as manufacturing technique for fixed-dose combination mini-matrices.

    Science.gov (United States)

    Dierickx, L; Saerens, L; Almeida, A; De Beer, T; Remon, J P; Vervaet, C

    2012-08-01

    The aim of this study was to develop a multilayer (core/coat) dosage form via co-extrusion, the core providing sustained drug release and the coat immediate drug release. In this study polymers were selected which can be combined in a co-extruded dosage form. Several thermoplastic polymers were hot-melt extruded and evaluated for processability and macroscopic properties (surface smoothness, die swell). Metoprolol tartrate (MPT) and hydrochlorothiazide (HCT) were incorporated as sustained and immediate release model drugs, respectively. Based on the polymer screening experiments a combination of polycaprolactone (core) and polyethylene oxide (coat) was selected for co-extrusion trials, taking into account their drug release profiles and extrusion temperature (70 °C). This combination (containing 10% HCT in the coat and 45% MPT in the core) was successfully co-extruded (diameter core: 3 mm/thickness coat: 0.5 mm). Adhesion between the two polymer layers was good. HCT release from the coat was complete within 30 min, while MPT release was sustained over 24 h (55%, 70%, 85% and 100% after 4, 8, 12 and 2 4h, respectively). DSC, XRD and Raman spectroscopy revealed that MPT remained crystalline during extrusion, whereas HCT was dissolved in the polyethylene oxide matrix. The in vivo study revealed no significant differences between the experimental formulation and the reference formulation (Zok-Zid tablet). Fixed-dose combination mini-tablets with good in vitro and in vivo performance were successfully developed by means of co-extrusion, using a combination of polycaprolactone and polyethylene oxide.

  17. Haematotoxic and reproductive toxicity of fixed dose combined anti-tuberculous agents: protective role of antioxidants in rats.

    Science.gov (United States)

    Awodele, O; Osunkalu, V O; Adejumo, I A; Odeyemi, A A; Ebuehi, O A T; Akintonwa, A

    2013-01-01

    Tuberculosis (TB) is the world's greatest infectious killer of women of reproductive age and the leading cause of death among people with HIV/AIDS. The major problem militating against the management of tuberculosis is the lack of compliance to medication by the infected patients as a result of multidrug needed to be taking daily leading to resistance. Occurrences of hepatic toxicity, teratogenicity, sperm quality damage, haematotoxicity and meningeal congestion of individual anti-tuberculous agents have been reported. The study is aimed to determine the reproductive and haematological toxicity of combined antituberculous agents and the modulatory role of antioxidants using animal model. Fifty rats (10 per group) were randomly allotted to five groups, consisting of the control, the fixed dose combined anti TB agents treated group, the fixed dose combined anti TB agents plus vitamin C treated group, the fixed dose combined anti TB agents plus vitamin E treated group and the fixed dose combined anti TB agents plus vitamin C plus vitamin E treated group. Therapeutic doses of the fixed dose combined anti TB agents (25 mg/kg/day), vitamin E (5 mg/kg) and vitamin C (8 mg/kg) were administered to the animals via oral gavage, daily over 28 days. After 28days, rats were sacrificed for internal macroscopic and histological examination of the organs, sperm analysis and haematological investigations were carried out. The results showed a significant increase (p < or = 0.05) in the levels of white blood cells (WBC), red blood cell (RBC) and haemoglobin (HB) of the combined anti-TB plus vitamins C or E treated groups compared with combined anti-TB treated group alone (56.34 +/- 0.11) that decreased the haematological parameters. A significant decrease (p < or = 0.05) in the sperm counts (22.26 +/- 0.02; 35.40 +/- 0.02) and motility (77.03 +/- 0.02; 94.50 +/- 0.01) of the combined anti-TB treated rats as compared with the control group were observed. The combined anti-TB plus

  18. 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

  19. Physical and chemical stability of expired fixed dose combination artemether-lumefantrine in uncontrolled tropical conditions

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    Hess Kimberly

    2009-02-01

    Full Text Available Abstract Background New artemisinin combination therapies pose difficulties of implementation in developing and tropical settings because they have a short shelf-life (two years relative to the medicines they replace. This limits the reliability and cost of treatment, and the acceptability of this treatment to health care workers. A multi-pronged investigation was made into the chemical and physical stability of fixed dose combination artemether-lumefantrine (FDC-ALU stored under heterogeneous, uncontrolled African conditions, to probe if a shelf-life extension might be possible. Methods Seventy samples of expired FDC-ALU were collected from private pharmacies and malaria researchers in seven African countries. The samples were subjected to thin-layer chromatography (TLC, disintegration testing, and near infrared Raman spectrometry for ascertainment of active ingredients, tablet integrity, and chemical degradation of the tablet formulation including both active ingredients and excipients. Results Seventy samples of FDC-ALU were tested in July 2008, between one and 58 months post-expiry. 68 of 70 (97% samples passed TLC, disintegration and Raman spectrometry testing, including eight samples that were post-expiry by 20 months or longer. A weak linear association (R2 = 0.33 was observed between the age of samples and their state of degradation relative to brand-identical samples on Raman spectrometry. Sixty-eight samples were retested in February 2009 using Raman spectrometry, between eight and 65 months post-expiry. 66 of 68 (97% samples passed Raman spectrometry retesting. An unexpected observation about African drug logistics was made in three batches of FDC-ALU, which had been sold into the public sector at concessional pricing in accordance with a World Health Organization (WHO agreement, and which were illegally diverted to the private sector where they were sold for profit. Conclusion The data indicate that FDC-ALU is chemically and

  20. Economic impact of switching to fixed-dose combination therapy for Japanese hypertensive patients: a retrospective cost analysis

    OpenAIRE

    Akazawa, Manabu; Fukuoka, Katsushi

    2013-01-01

    Background The prescription of fixed-dose combinations (FDC) of antihypertensive drugs has increased rapidly since the relaxation of the prescription-term restriction. In this study, we used the opportunity of this policy change in Japan as an instrument to assess the causal impact of switching to FDC on hypertensive treatment costs. Methods Claims data from 64 community pharmacies located in Tokyo were used to identify hypertensive patients under continuous treatment with angiotensin-recepto...

  1. Management of hypertension with fixed dose combinations of candesartan cilexetil and hydrochlorothiazide: patient perspectives and clinical utility

    Directory of Open Access Journals (Sweden)

    Thomas Mengden

    2009-11-01

    Full Text Available Thomas Mengden1, Sakir Uen1, Peter Bramlage21Centre of Vascular Medicine, Herz- und Gefäß-Campus, Bad Nauheim, Germany; 2Institute for Cardiovascular Pharmacology and Epidemiology, Mahlow, GermanyAbstract: Hypertension treatment and control is largely unsatisfactory when guideline-defined blood pressure goal achievement and maintenance are considered. Patient- and physician-related factors leading to non-adherence interfere in this respect with the efficacy, tolerability, and convenient use of pharmacological treatment options. Blockers of the renin–angiotensin system (RAS are an important component of antihypertensive combination therapy. Thiazide-type diuretics are usually added to increase the blood pressure lowering efficacy. Fixed drug–drug combinations of both principles like candesartan/hydrochlorothiazide (HCTZ are highly effective in lowering blood pressure while providing improved compliance, a good tolerability, and largely neutral metabolic profile. Comparative studies with losartan/HCTZ have consistently shown a higher clinical efficacy with the candesartan/HCTZ combination. Data on the reduction of cardiovascular endpoints with fixed dose combinations of antihypertensive drugs are however scarce, as are the data for candesartan/HCTZ. But many trials have tested candesartan versus a non-RAS blocking comparator based on a standard therapy including thiazide diuretics. The indications tested were heart failure and stroke and particular emphasis was put on elderly patients or those with diabetes. In patients with heart failure, for example, the fixed dose combination might be applied in patients in whom individual titration resulted in a dose of 32 mg candesartan and 25 mg HCTZ which can then be combined into one tablet to increase compliance with treatment. Also in patients with stroke the fixed dose combination might be used in patients in whom maintenance therapy with both components is considered. Taken together candesartan

  2. 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...... endpoint was the mean change in the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) total score from baseline to week 12. Secondary efficacy endpoints included remission (defined as Y-BOCS total score

  3. Treatment of hyperthyroidism by 131-iodine; Traitement des hyperthyroidies par l'iode 131: dose calculee versus dose fixe

    Energy Technology Data Exchange (ETDEWEB)

    Fieffe, S.; Cuif-Joba, A.; Testard, A.; Fortuna, I.; Pocharta, J.M.; Papathanassioua, D.; Schvartz, C. [Service d' endocrinologie et medecine nucleaires, institut Jean-Godinot, 1, rue du General Koeing, 51056 Reims, (France)

    2009-05-15

    In a first time, we chose to modify the dose to be administered, on using always the Marinelli formula but on increasing the absorbed dose. In a second time, we wanted to simplify the determination of the dose to be administered by modulating it only in function of the thyroid volume. Two groups of patients were managed for hyperthyroidism recurrence. In a first group the iodine dose ({sup 131}I) was determined with the help of the simplified Marinelli formula: chosen absorbed dose was 150 Gy, gland volume determined by echography, measurement of the fixation at the sixth hour. In the second group, the thyroid volume was determined by echography. The patients with a thyroid from 5 to 30 g received 185 MBq, from 30 to 50 g 370 MBq and superior to 50 g 555 MBq of iodine 131. The two groups of patients have the same characteristics. the results of treatment by iodine 131, evaluated on the dosages of T4L and TSH at three and six months, show the preservation of euthyroidism or the passage in hypothyroidism among 94% of patients in the group 1 and 80% of patients in the group 2. These results are not significantly different. The easiness of the realisation of the treatment in the group 2 lead us to continue this simplified therapy scheme that allows equally to improve the radiation protection of medical personnel by avoiding the use of iodine 131. (N.C.)

  4. A Case of Self-treatment Induced Recurrent Fixed Drug Eruptions Associated with the Use of Different Fixed Dose Combinations of Fluoroquinolone-Nitroimidazole

    Directory of Open Access Journals (Sweden)

    Agnik Pal

    2014-11-01

    Full Text Available A young male patient used fixed dose combinations of different fluoroquinolones and nitroimidazoles several times in the last few years for self-treating repeated episodes of diarrhea and loose motion. Each time, he experienced fixed drug eruptions that increased in number and severity on subsequent occasions. Suspecting association between the drug and the rashes, the patient each time discontinued the treatment prematurely, and preferred to switch to a similar formulation next time, but with different molecules of fluoroquinolone (ciprofloxacin or ofloxacin and nitroimidazole (tinidazole or ornidazole.He could not however avoid the rash. This time the patient presented with multiple, round-to-oval, well-defined, hyperpigmented cutaneous patches of different dimensions, all over the body. He appeared to have run out of options and therefore consulted us seeking advice on how he should treat himself next time he suffered from diarrhea. Causality assessment by Naranjo’s algorithm revealed a definite relationship between the cutaneous adverse reaction and the offending drug. He was counselled regarding medication in general and advised, in particular, to avoid the tendency to self-treat any future episode of diarrhea.

  5. An observational, prospective, two-cohort comparison of a fixed versus variable dosing strategy of prothrombin complex concentrate to counteract vitamin K antagonists in 240 bleeding emergencies.

    Science.gov (United States)

    Khorsand, Nakisa; Veeger, Nic J G M; van Hest, Reinier M; Ypma, Paula F; Heidt, Jeroen; Meijer, Karina

    2012-10-01

    Despite years of experience with vitamin K antagonist-associated bleeding events, there is still no evidence to help identify the optimal treatment with prothrombin complex concentrates. Variable dosing and fixed dose strategies are being used. In this observational prospective two-cohort study, we aimed to assess the non-inferiority of a low fixed PCC dose (1,040 IU Factor IX) compared to the registered variable dosing regimen based on baseline International Normalized Rate, bodyweight, and target International Normalized Rate, to counteract vitamin K antagonists in a bleeding emergency in a daily clinical practice setting. Non-inferiority of the fixed prothrombin complex concentrate dose was hypothesized with a margin of 4%. Main end points were proportion of patients reaching the target International Normalized Rate (complex concentrate treatment, and successful clinical outcome. Target International Normalized Rate was reached in 92% of the fixed dose patients (n=101) versus 95% of variable dose patients (n=139) resulting in a risk difference of -2.99% (90% CI: - 8.6 to 2.7) (non-inferiority not confirmed). Clinical outcome was successful in 96% and 88% of fixed versus variable dose, respectively, with a risk difference of 8.3% (90% CI: 2.7-13.9; non-inferiority confirmed). Although a lower fixed prothrombin complex concentrate dose was associated with successful clinical outcome, fewer patients reached the target International Normalized Rate.

  6. 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

  7. [Medical expert consensus in AH on the clinical use of triple fixed-dose antihypertensive therapy in Spain].

    Science.gov (United States)

    Mazón, P; Galve, E; Gómez, J; Gorostidi, M; Górriz, J L; Mediavilla, J D

    The opinion of experts (different specialties) on the triple fixed-dose antihypertensive therapy in clinical practice may differ. Online questionnaire with controversial aspects of the triple therapy answered by panel of experts in hypertension (HT) using two-round modified Delphi method. The questionnaire was completed by 158 experts: Internal Medicine (49), Nephrology (26), Cardiology (83). Consensus was reached (agreement) on 27/45 items (60%); 7 items showed differences statistically significant. Consensus was reached regarding: Predictive factors in the need for combination therapy and its efficacy vs. increasing the dose of a pretreatment, and advantage of triple therapy (prescription/adherence/cost/pressure control) vs. free combination. This consensus provides an overview of the clinical use of triple therapy in moderate-severe and resistant/difficult to control HT. Copyright © 2016 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. Benefits of Fixed Dose Combination of Ramipril/Amlodipine in Hypertensive Diabetic Patients: A Subgroup Analysis of RAMONA Trial

    Institute of Scientific and Technical Information of China (English)

    Gabor Simonyi

    2016-01-01

    Background:Combination ofangiotensin-converting enzyme inhibitors and calcium channel blockers has been successfully used in the antihypertensive therapy for many years.Fixed dose combinations of ramipril/amlodipine have a benefit effect for patients to achieve target blood pressure (BP).This study aimed to assess the efficacy and safety of fixed dose combinations of ramipril and amlodipine (EgiramlonR) in hypertensive diabetic patients.Methods:Hypertensive diabetic patients who were enrolled into the RAMONA trial were included in this open,prospective,Phase Ⅳ observational clinical study.Patients had mild-to-moderate hypertension and failed to reach target BP levels through their previous therapy.During the four months of observation,patients took part in three visits (1 st day =visit 1,1st month =visit 2,and 4th month =visit 3) where they received a fixed dose combination of 5/5,5/10,10/5,or 10/10 mg ramipril/amlodipine,respectively,with the possibly required dose titrations,based on the decision of their attending physician.Target BP for diabetic patients was < 140/85 mmHg.BP levels were measured in all visits,by taking two readings at 2-min interval.Laboratory tests including full blood count,renal function test,electrolytes,blood glucose,serum cholesterol,uric acid,triglycerides,liver function test,creatinine kinase,and midstream urinalysis were performed at visit 1 and visit 3.Results:The 6423 patients completed the study.Among these patients,1276 (19.9%) patients suffered from type 2 diabetes mellitus.The mean age of these diabetic patients was 64.2 ± 10.0 years;707 (55.4%) patients were males.Target BP was achieved by 891 (69.8%) of diabetic patients at visit 3 (primary endpoint).BP decreased from 157.5/91.3 ± 9.6/7.6 mmHg (visit 1) to 130.9/79.6 ± 7.4/5.8 mmHg (visit 3).As for the secondary endpoint of the study,total cholesterol decreased from 5.50 ± 1.13 mmol/L (visit 1) to 5.20 ± 0.95 mmol/L (P =0.000),low-density lipoprotein cholesterol

  9. Critical appraisal of a fixed combination of esomeprazole and low dose aspirin in risk reduction

    Directory of Open Access Journals (Sweden)

    Ravi Vachhani

    2010-06-01

    Full Text Available Ravi Vachhani1, Doumit Bouhaidar1, Alvin Zfass1, Bimaljit Sandhu1, Ali Nawras21Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University Medical Center, Richmond, Virginia 23298–0341, USA; 2Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The University of Toledo Medical Center, Toledo, Ohio 43606-3390, USAAbstract: Low dose aspirin (≤325 mg is routinely used for primary and secondary prophylaxis of cardiovascular and cerebrovascular events. The use of low dose aspirin is associated with two-to four-fold greater risk of symptomatic or complicated peptic ulcers. Risk factors associated with low dose aspirin induced gastrointestinal toxicity includes prior history of ulcer or upper gastrointestinal (GI bleeding, concomitant use of other nonsteroidal anti-inflammatory drugs, corticosteroid or warfarin, dual antiplatelet therapy, Helicobacter pylori (H. pylori infection, and advanced age. Esomeprazole, like other proton pump inhibitors (PPIs is very effective in decreasing the risk of aspirin induced gastrointestinal toxicity. Although evidence to support esomeprazole or other PPIs for primary prophylaxis in aspirin induced gastrointestinal toxicity is limited, its role in secondary prophylaxis is well established.Keywords: esomeprazole, proton pump inhibitors, low dose aspirin, gastrointestinal toxicity, gastrointestinal bleeding

  10. Efficacy and tolerability between an olmesartan/amlodipine fixed-dose combination and an amlodipine double dose in mild to moderate hypertension

    Directory of Open Access Journals (Sweden)

    Tsung-Hsien Lin

    2013-05-01

    Full Text Available Fixed-dose combinations (FDCs are one of the options for improving blood pressure (BP goal attainment. We enrolled 141 patients and evaluated the efficacy and safety between a fixed dose of olmesartan/amlodipine (OA and a double dose of amlodipine (DA for treating mild to moderate hypertension after amlodipine monotherapy failure. After at least 2 weeks of monotherapy failure, the patients were randomized to receive either OA or DA for 8 weeks. We compared the systolic blood pressure (SBP-lowering efficacy of the OA and DA using both an office BP and an ambulatory blood pressure monitoring (ABPM device. The intent-to-treat analysis found that the early (2nd week and final visit (8th week SBP reductions were significantly greater in those patients receiving OA (n = 70 than DA (n = 71 (17.57 ± 15.49 vs. 10.46 ± 13.36 and 24.89 ± 14.09 vs. 17.03 ± 13.27 mmHg, p = 0.002 and 0.001, respectively. Among those using ABPM, the patients with 8-week OA had a greater SBP-lowering effect in comparison with those on DA (14.08 ± 10.74 vs. 6.32 ± 10.21, p = 0.018. Both treatment strategies were well tolerated. This study showed that an OA FDC is more effective than DA in reducing SBP for mild to moderate hypertension after the failure of amlodipine monotherapy.

  11. Safety and efficacy of a fixed-dose cyclosporin microemulsion (100 mg) for the treatment of psoriasis.

    Science.gov (United States)

    Shintani, Yoichi; Kaneko, Natumi; Furuhashi, Takuya; Saito, Chiyo; Morita, Akimichi

    2011-10-01

    Cyclosporin is a second-line modality for the treatment of psoriasis. The long-term efficacy of cyclosporin and potential adverse side-effects, however, are a concern to patients. Therefore, a cyclosporin microemulsion (Neoral), which is steadily absorbed at an ultra-low dosage (1-2 mg/kg per day) or low dosage (2-3 mg/kg per day), is currently recommended. The dose must be calculated based on patient bodyweight and the blood concentration monitored regularly, which is time-consuming. Furthermore, the concentration is related to the safety profile, but not to efficacy. We examined whether a fixed-dose cyclosporin microemulsion (100 mg/day) is effective for treating psoriasis. Enrolled patients (n = 40) were given either 100 mg cyclosporin emulsion once daily (group A) or 50 mg twice daily (group B), regardless of patient weight and condition, before meals in a randomized controlled study. Patient bodyweight ranged 50-80 kg. We assessed the serum cyclosporin concentration 1 h after administrating the medicine (C1 score), Psoriasis Area and Severity Index (PASI) score, quality of life, and the results of regular blood examinations. The improvement rate was 69.4 ± 4.8% in group A and 73.4 ± 4.3% in group B. PASI-50 was achieved by 82% in group A and 84% in group B. At 6 weeks, the number of patients with PASI-50 was significantly higher in group A than in group B. PASI-75 and -90 were also achieved in both groups with no significant difference between groups. Administration of a fixed-dose cyclosporin microemulsion (100 mg/day) is practical for second-line psoriasis treatment. © 2011 Japanese Dermatological Association.

  12. An open randomized clinical trial in comparing two artesunate-based combination treatments on Plasmodium falciparum malaria in Nigerian children: artesunate/sulphamethoxypyrazine/pyrimethamine (fixed dose over 24 hours versus artesunate/amodiaquine (fixed dose over 48 hours

    Directory of Open Access Journals (Sweden)

    Sowunmi Akintunde

    2010-12-01

    Full Text Available Abstract Background Several studies have demonstrated the efficacy of artemisinin-combination therapy (ACT across malaria zones of the world. Fixed dose ACT with shorter courses and fewer tablets may be key determinants to ease of administration and compliance. Methods Children aged one year to 13 years presenting with uncomplicated Plasmodium falciparum malaria were recruited in Ibadan, south-western Nigeria. A total of 250 children each were randomly assigned to receive three doses of artesunate/sulphamethoxypyrazine/pyrimethamine (AS + SMP (12 hourly doses over 24 hours or three doses of artesunate/amodiaquine (AS + AQ (daily doses over 48 hours. Efficacy and safety of the two drugs were assessed using a 28-day follow-up and the primary outcome was PCR- corrected parasitological cure rate and clinical response. Results There were two (0.4% early treatment failures, one in each treatment arm. The PCR corrected cure rates for day 28 was 97.9% in the AS + AQ arm and 95.6% in the AS + SMP arm (p = 0.15. The re-infection rate was 1.7% in the AS + AQ arm and 5.7% in the AS + SMP arm (p = 0.021. The fever clearance time was similar in the two treatment groups: 1 - 2 days for both AS + SMP and AS + AQ (p = 0.271. The parasite clearance time was also similar in the two treatment groups with 1 - 7 days for AS + SMP and 1 - 4 days for AS + AQ (p = 0.941. The proportion of children with gametocytes over the follow-up period was similar in both treatment groups. Serious Adverse Events were not reported in any of the patients and in all children, laboratory values (packed cell volume, liver enzymes, bilirubin remained within normal levels during the follow-up period but the packed cell volume was significantly lower in the AS + SMP group. Conclusions This study demonstrates that AS + SMP FDC given as three doses over 24 hours (12-hour intervals has similar efficacy as AS + AQ FDC given as three doses over 48 hours (24-hour interval for the treatment of

  13. Pharmacokinetics of fixed-dose combination of tenofovir disoproxil fumarate, lamivudine, and efavirenz: results of a randomized, crossover, bioequivalence study.

    Science.gov (United States)

    Abhyankar, Dhiraj; Shedage, Ashish; Gole, Milind; Raut, Preeti

    2016-06-17

    The objective of this study was to assess the bioequivalence between a fixed-dose combination of tenofovir disoproxil fumarate/lamivudine/efavirenz 300/300/600 mg and the individual innovator products. A randomized, balanced, open-label, two-sequence, two-treatment, two-period, single dose, crossover study in 48 healthy adults was conducted. Dosing was separated by a washout period of 32 days. Twenty-seven blood samples were collected in each period from pre-dose to 72 h post-dose. The data of 45 subjects were analyzed for pharmacokinetics and safety. Ninety percent CIs of geometric mean ratio on Cmax, AUC0-t, and AUC0-inf for tenofovir and lamivudine and on Cmax and AUC0-72 for efavirenz were within the acceptance criteria (80-125%). For tenofovir disoproxil fumarate, the Tmax, Kel, and t1/2 values for the test and reference products were 1.02 versus 0.91 h, 0.04 versus 0.04/h, 18.67 versus 18.46 h, respectively. For lamivudine, the Tmax, Kel, and t1/2 values were: 1.38 versus 1.30 h, 0.21 versus 0.19/h, 3.44 versus 3.91 h, respectively. For efavirenz, the Tmax values for the test and reference products were 3.71 and 3.65 h, respectively. Both the treatments were well tolerated. Our findings suggest that the tested formulation is bioequivalent to the innovators' formulations, and both treatments were well tolerated.

  14. An observational, prospective, two-cohort comparison of a fixed versus variable dosing strategy of prothrombin complex concentrate to counteract vitamin K antagonists in 240 bleeding emergencies

    NARCIS (Netherlands)

    Khorsand, Nakisa; Veeger, Nic J. G. M.; van Hest, Reinier M.; Ypma, Paula F.; Heidt, Jeroen; Meijer, Karina

    2012-01-01

    Background Despite years of experience with vitamin K antagonist-associated bleeding events, there is still no evidence to help identify the optimal treatment with prothrombin complex concentrates. Variable dosing and fixed dose strategies are being used. In this observational prospective two-cohort

  15. Relation of blood cyanide to plasma cyanocobalamin concentration after a fixed dose of hydroxocobalamin in cyanide poisoning.

    Science.gov (United States)

    Houeto, P; Hoffman, J R; Imbert, M; Levillain, P; Baud, F J

    1995-09-02

    Hydroxocobalamin combines with cyanide to form cyanocobalamin. We hypothesised that the amount of cyanocobalamin formed after a fixed dose of hydroxocobalamin given for cyanide poisoning would correlate with initial blood cyanide concentration. We determined blood cyanide concentration in 12 patients exposed to residential fires, and compared this with markers of the amount of cyanocobalamin formed after treatment with 5 g intravenous hydroxocobalamin. All relationships were highly correlated (r2 0.79-0.95), for the whole group, and there appeared to be an almost linear relationship for the 9 patients with initial cyanide concentration below 40 mumol/L. Above this concentration, no further cyanocobalamin was formed from a single 5 g dose of hydroxocobalamin. In one patient with initial blood cyanide concentration of 96 mumol/L, however, plasma cyanocobalamin concentration approximately doubled after a second 5 g dose of hydroxocobalamin. 5 g of hydroxocobalamin appears capable of binding all available cyanide ions for blood cyanide concentrations up to about 40 mumol/L. Beyond this, more hydroxocobalamin must be given for remaining cyanide ions to be bound. This information will allow clinicians to use rapidly measurable plasma cyanocobalamin concentrations to gauge severity of exposure and evaluate adequacy of treatment.

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

    Science.gov (United States)

    Son, Hankil; Roh, Hyerang; Lee, Donghwan; Chang, Heechul; Kim, Junku; Yun, Chohee; Park, Kyungsoo

    2013-07-01

    Rosuvastatin, a lipid-lowering agent, has been widely used with olmesartan, a long-acting angiotensin II receptor blocker, indicated for the treatment of dyslipidemia accompanied by hypertension. A fixed-dose combination (FDC) tablet of these 2 drugs was recently developed to enhance the dosing convenience and to increase patient compliance while yielding pharmacokinetic profiles comparable to coadministration of each drug as individual tablets. The goal of present study was to compare the pharmacokinetic profiles of single-dose administration of an FDC tablet containing rosuvastatin/olmesartan 20/40 mg (test formulation) with coadministration of a rosuvastatin 20-mg tablet and a olmesartan 40-mg tablet (reference formulation) in healthy Korean male volunteers, for the purpose of determining bioequivalence. This single-dose, randomized, open-label, 2-period crossover study enrolled subjects aged 20 to 50 years and within 20% of ideal body weight. Each subject received a single dose of the test and reference formulations orally in a fasted state, with a 7-day washout period between the administrations. Blood samples were collected up to 72 hours after dosing, and pharmacokinetic parameters were determined for rosuvastatin, its active metabolite (N-desmethyl rosuvastatin), and olmesartan. Bioequivalence was concluded if the 90% CIs of the geometric mean ratios for the primary pharmacokinetic parameters were within the predetermined range of 80% to 125%. Adverse events (AEs) were evaluated based on subject interviews and physical examinations. Among the 58 enrolled subjects, 54 completed the study. The 90% CIs of the geometric mean ratios of the primary pharmacokinetic parameters were as follows: rosuvastatin: AUC(last), 85.60% to 97.40% and C(max), 83.16% to 98.21%; N-desmethyl rosuvastatin: AUC(last), 82.08% to 93.45% and C(max), 79.23% to 93.41%; and olmesartan: AUC(last), 97.69% to 105.69% and C(max), 100.35% to 109.42%. The most frequently noted AE was headache

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

    Science.gov (United States)

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

    2015-10-01

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

  18. Atomoxetine treatment for nicotine withdrawal: a pilot double-blind, placebo-controlled, fixed-dose study in adult smokers

    Directory of Open Access Journals (Sweden)

    Silverstone Peter H

    2012-03-01

    Full Text Available Abstract Background Many effective treatments for nicotine addiction inhibit noradrenaline reuptake. Three recent studies have suggested that another noradrenaline reuptake inhibitor, atomoxetine, may reduce smoking behaviors. Methods The present double-blind, placebo-controlled, fixed-dose study was carried out over 21 days during which administration of 40 mg atomoxetine was compared to placebo in 17 individuals. Of these, nine were randomized to atomoxetine and eight to placebo. Baseline and weekly measurements were made using the Cigarette Dependence Scale (CDS, Cigarette Withdrawal Scale (CWS, Questionnaire of Smoking Urges (QSU, reported number of cigarettes smoked, and salivary cotinine levels. Results The study results showed that all those on placebo completed the study. In marked contrast, of the nine individuals who started on atomoxetine, five dropped out due to side effects. In a completer analysis there were statistically significant differences at 14 and 21 days in several measures between the atomoxetine and placebo groups, including CDS, CWS, QSU, number of cigarettes smoked (decreasing to less than two per day in the treatment group who completed the study, and a trend towards lower mean salivary cotinine levels. However, these differences were not seen in a last observation carried forward (LOCF analysis. Conclusions In summary, this is the first study to examine the use of atomoxetine in non-psychiatric adult smokers for a period of more than 7 days, and the findings suggest that atomoxetine might be a useful treatment for nicotine addiction. However, the dose used in the current study was too high to be tolerated by many adults, and a dose-finding study is required to determine the most appropriate dose for future studies of this potential treatment for smoking cessation.

  19. Simultaneous And Extended Delivery Of Stavudine, Lamivudine And Nevirapine In Fixed Dose Combination Using Sandwiched Osmotic Tablets For Hiv Therapy.

    Science.gov (United States)

    Priya, M Ranga; Rajendran, N N

    2015-01-01

    Current HIV-therapy recommends combination of stavudine, lamivudine and nevirapine. Stavudine and lamivudine are administered as fixed combination while nevirapine as separate dosage form which often results in poor compliance and adherence to therapy by patients and therefore, there is a need to develop dosage forms that can overcome the problems of currently available dosage forms for treatment of HIV infection. The present study developed a single unit osmotic system for simultaneous and extended delivery of stavudine, lamivudine and nevirapine that can ensure patients compliance and adherence to HIV-therapy. Sandwich osmotic pump tablets (SOPTs) of stavudine, lamivudine and nevirapine in fixed dose combination were designed and evaluated for the effect of variables such as PEO (polymer), KCl (osmogen), and orifice diameter on the physicochemical characteristics and the release behavior of the drugs. A 24 h zero order release of stavudine, lamivudine and nevirapine from the formulations was observed and the release rate of the drugs was found to be affected by PEO, KCl, and orifice diameter. The in vitro release data of SOPT correlated with in vivo predictions by super - position method. The results of the study propose that a single unit osmotic system (SOPT) of stavudine, lamivudine and nevirapine is beneficial to overcome the disadvantages of currently available dosage forms for effective control of HIV infection.

  20. Adherence to antihypertensive therapy with fixed-dose amlodipine besylate/benazepril HCl versus comparable component-based therapy.

    Science.gov (United States)

    Taylor, Addison A; Shoheiber, Omar

    2003-01-01

    Adhering to medication regimens has the potential to significantly improve clinical outcomes for persons with high blood pressure. A patient-related factor likely to affect adherence to treatment is the convenience of the prescribed drug regimen. The authors hypothesized that medication adherence would be superior and cost benefits would accrue in subjects who receive a once-daily, single-capsule, fixed-dose combination product for blood pressure control, compared with subjects who receive a similar regimen of separate components. A managed care organization that provides benefits for members enrolled in various health plans provided the data for this retrospective analysis. The database was used to assess medication adherence patterns for two groups of hypertensive subjects. Group 1 included subjects who had been prescribed the single-capsule, fixed-dose combination of amlodipine besylate/benazepril HCl. Group 2 comprised subjects who had been prescribed a regimen including an angiotensin-converting enzyme inhibitor and a dihydropyridine calcium channel blocker as separate drugs. Adherence was measured by the medication possession ratio, and medical resource utilization by the two groups was assessed during the study period. Group 1 (n=2754) and Group 2 (n=2978) were balanced with regard to age (mean, 53 years; range, 18-64 years) and sex (men, 50%; women, 50%). The overall medication possession ratio for Group 1 was significantly higher than that for Group 2 (80.8% vs. 73.8%; pamlodipine/benazepril HCl demonstrated significantly better medication adherence and required fewer medical resources than did subjects receiving an angiotensin-converting enzyme inhibitor and a dihydropyridine calcium channel blocker as separate components.

  1. Profile of once-daily darunavir/cobicistat fixed-dose combination for the treatment of HIV/AIDS

    Directory of Open Access Journals (Sweden)

    Navarro J

    2016-10-01

    Full Text Available Jordi Navarro, Adrian Curran Infectious Diseases Department, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain Abstract: Efficacy is the main objective of antiretroviral treatment and adherence is one of the cornerstones to achieve it. For this reason, treatment simplification is of key importance with regard to antiretroviral regimens. Rezolsta® (darunavir/cobicistat is the first fixed-dose combination containing a protease inhibitor approved for HIV treatment. This coformulation includes darunavir, a protease inhibitor that has shown its efficacy and safety in naïve and treatment-experienced patients, and cobicistat, the new pharmacokinetic enhancer that is expected to replace ritonavir. Bioequivalence between ritonavir and cobicistat as darunavir boosters has been shown in studies involving healthy volunteers. Furthermore, efficacy and safety of darunavir/cobicistat observed in phase III studies, including naïve and pretreated patients without darunavir-associated resistance mutations, are comparable to historical data of darunavir/ritonavir 800/100 mg once-daily formulation. Adverse events with darunavir/cobicistat are scarce and mild, and basically include skin reactions and gastrointestinal disturbances. Although small increases in plasma creatinine are expected in patients receiving cobicistat due to the inhibition of creatinine transporters in kidney tubules, actual glomerular filtrate rate remains unaltered. Cobicistat does not have an inducer effect on metabolic pathways and shows much more selective inhibition than ritonavir. Therefore, isoenzyms different from CYP3A4 are supposed to be less affected by cobicistat, and thus fewer drug–drug interactions are expected. Keywords: darunavir, cobicistat, fixed-dose combination, HIV infection, antiretroviral treatment

  2. Repaglinide/metformin fixed-dose combination to improve glycemic control in patients with type 2 diabetes: an update

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    Robert G Moses

    2010-05-01

    Full Text Available Robert G MosesClinical Trials and Research Unit, South East Sydney and Illawarra Area Health Service, New South Wales, AustraliaAbstract: Type 2 diabetes is a progressive disease associated with high levels of morbidity and mortality and for which there is both a large and growing prevalence worldwide. Lifestyle advice plus metformin is commonly recommended initially to manage hyperglycemia and to minimize the risk of vascular complications. However, additional agents are required when glycemic targets cannot be achieved or maintained due to the progressive nature of the disease. Repaglinide/metformin fixed-dose combination (FDC therapy (PrandiMet®; Novo Nordisk, Bagsværd, Denmark has been approved for use in the USA. This FDC is a rational second-line therapy given the complementary mechanisms of action of the components. Repaglinide is a rapidly absorbed, short-acting insulin secretagogue targeting postprandial glucose excursions; metformin is an insulin sensitizer with a longer duration of action that principally regulates basal glucose levels. A pivotal, 26-week, randomized study with repaglinide/metformin FDC therapy has been conducted in patients experiencing suboptimal control with previous oral antidiabetes therapy. Repaglinide/metformin FDC improved glycemic control and weight neutrality without adverse effects on lipid profiles. There were no major hypoglycemic episodes and patients expressed greater satisfaction with repaglinide/metformin FDC than previous treatments. Repaglinide/metformin FDC is expected to be more convenient than individual tablets for patients taking repaglinide and metformin in loose combination, and it is expected to improve glycemic control in patients for whom meglitinide or metformin monotherapies provide inadequate control.Keywords: type 2 diabetes, metformin, repaglinide, PrandiMet®, fixed-dose combination

  3. Fixed-dose combinations in type 2 diabetes – role of the canagliflozin metformin combination

    Science.gov (United States)

    Fleming, Joshua W; Fleming, Laurie W; Davis, Courtney S

    2015-01-01

    Canagliflozin–metformin is one of the newest combination therapies available for the treatment of type 2 diabetes mellitus (T2DM). Canagliflozin is an inhibitor of the sodium–glucose co-transporter 2 which causes an increase in the urinary excretion of glucose. In the present article, we review the safety and efficacy of canagliflozin and metformin from data obtained from Phase III metformin add-on therapy clinical trials as there are no studies to date that specifically evaluate the combination of metformin and canagliflozin. Trials included in this review were dual-therapy trials of subjects who were already taking background metformin and were assigned to receive canagliflozin, glimepiride, or sitagliptin. The addition of canagliflozin to metformin resulted in a decrease in HbA1c of 0.73%–0.93%. Canagliflozin 100 mg was considered to be non-inferior to glimepiride and sitagliptin 100 mg with the canagliflozin 300 mg dose being statistically superior to sitagliptin and glimepiride. Other advantages of the use of canagliflozin are reduction in weight (3.3–4.0 kg) and systolic blood pressure (3.3–4.7 mmHg). The primary disadvantages are potential genital mycotic infections, hypotension, and gastrointestinal side effects from metformin. All things considered, this combination appears to be safe and effective in clinical trials and represents a promising option for the treatment of T2DM. PMID:26150733

  4. Derivative Spectrophotometric Method for Estimation of Antiretroviral Drugs in Fixed Dose Combinations

    Directory of Open Access Journals (Sweden)

    Mohite P.B.

    2012-06-01

    Full Text Available Purpose: Lamivudine is cytosine and zidovudine is cytidine and is used as an antiretroviral agents. Both drugs are available in tablet dosage forms with a dose of 150 mg for LAM and 300 mg ZID respectively. Method: The method employed is based on first order derivative spectroscopy. Wavelengths 279 nm and 300 nm were selected for the estimation of the Lamovudine and Zidovudine respectively by taking the first order derivative spectra. The conc. of both drugs was determined by proposed method. The results of analysis have been validated statistically and by recovery studies as per ICH guidelines. Result: Both the drugs obey Beer’s law in the concentration range 10-50 μg mL-1,for LAM and ZID; with regression 0.9998 and 0.9999, intercept – 0.0677 and – 0.0043 and slope 0.0457 and 0.0391 for LAM and ZID, respectively.The accuracy and reproducibility results are close to 100% with 2% RSD. Conclusion: A simple, accurate, precise, sensitive and economical procedures for simultaneous estimation of Lamovudine and Zidovudine in tablet dosage form have been developed.

  5. Clinical benefit of fixed-dose dual bronchodilation with glycopyrronium and indacaterol once daily in patients with chronic obstructive pulmonary disease: a systematic review

    Directory of Open Access Journals (Sweden)

    Ulrik CS

    2014-04-01

    Full Text Available Charlotte Suppli UlrikDepartment of Respiratory Medicine, Hvidovre Hospital and University of Copenhagen, Hvidovre, DenmarkBackground 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 dual bronchodilator combination of indacaterol and glycopyrronium bromide in patients suffering from COPD.Methods: This study comprised a systematic review of randomized controlled trials identified through systematic searches of different databases of published trials.Results: Nine trials (6,166 participants were included. Fixed-dose once-daily indacaterol/glycopyrronium seems to be safe and well tolerated in patients with COPD. Compared with single therapy with other long-acting bronchodilators (indacaterol, glycopyrronium, and tiotropium and fixed-combination long-acting β2-agonist/inhaled corticosteroid (salmeterol/fluticasone twice daily, once-daily fixed-dose indacaterol/glycopyrronium has clinically important effects on symptoms, including dyspnea score, health status, level of lung function, and rate of moderate or severe exacerbations in patients with moderate-to-very severe COPD (Global initiative 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/glycopyrronium and tiotropium.Conclusion: Fixed-dose indacaterol/glycopyrronium has clinically relevant effects on important COPD outcome measures and is, in general, superior to therapy with a single long-acting bronchodilator (with or without inhaled corticosteroid indicating long-acting dual bronchodilation as a potential important maintenance

  6. Clinical benefit of fixed-dose dual bronchodilation with glycopyrronium and indacaterol once daily in patients with chronic obstructive pulmonary disease: a systematic review.

    Science.gov (United States)

    Ulrik, Charlotte Suppli

    2014-01-01

    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 dual bronchodilator combination of indacaterol and glycopyrronium bromide in patients suffering from COPD. This study comprised a systematic review of randomized controlled trials identified through systematic searches of different databases of published trials. Nine trials (6,166 participants) were included. Fixed-dose once-daily indacaterol/glycopyrronium seems to be safe and well tolerated in patients with COPD. Compared with single therapy with other long-acting bronchodilators (indacaterol, glycopyrronium, and tiotropium) and fixed-combination long-acting β2-agonist/inhaled corticosteroid (salmeterol/fluticasone twice daily), once-daily fixed-dose indacaterol/glycopyrronium has clinically important effects on symptoms, including dyspnea score, health status, level of lung function, and rate of moderate or severe exacerbations in patients with moderate-to-very severe COPD (Global initiative 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/glycopyrronium and tiotropium. Fixed-dose indacaterol/glycopyrronium has clinically relevant effects on important COPD outcome measures and is, in general, superior to therapy with a single long-acting bronchodilator (with or without inhaled corticosteroid) indicating long-acting dual bronchodilation as a potential important maintenance therapeutic option for patients with symptomatic COPD, possibly also for the treatment of naïve patients.

  7. Effectiveness of Fixed Dose Radioactive Iodine (RAI for the Treatment of Hyperthyroidism: Experience of a Teaching Hospital in South West Nigeria

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    Karounwi Omotayo Ogunjobi

    2013-08-01

    Full Text Available Objective: Using radioactive iodine (RAI as the first line therapy for Graves’ hyperthyroidism and as the treatment of choice for relapsed Graves’ disease is increasing in recent times. However, there has been little consensus on the most appropriate dose to use. So this study is to determine the response of hyperthyroidism to fixed doses of 370 MBq and 555 MBq RAI therapies and determine the incidence of hypothyroidism at 6 months post therapy. Methods: Hyperthyroid patients’ case records treated with radioiodine was retrospectively reviewed to determine the response rate of hyperthyroidism to the two fixed dose regimens. Statistical analysis was done with SPSS version 15.0 and the level of statistical significance was taken as p<0.05. Forty subjects, 6 males (15% and 34 females (85% received RAI therapy for Graves’ hyperthyroidism, mean age was 49.4 years (range, 25-75years. The thyroid function status at 6 months post therapy was available for all subjects. 24 patients (60% received 370 MBq while 16 patients (40% received 555 MBq. Results: The response for fixed doses of 370 MBq and 555 MBq were similar (100%. Also, the incidence of hypothyroidism in these subjects which was 66.6% with fixed dose of 370 MBq and 62.5% with fixed dose of 555 MBq within 6 months post RAI therapy were similar. Conclusion: SRAI is highly effective for the treatment of hyperthyroidism, with a cure rate of 100%. However, it has proved impossible to determine a fixed dose regimen for individual patients accurately to guarantee an euthyroid state. This is because hypothyroidism is a natural predictable sequel of RAI therapy.

  8. 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.

  9. Replicate study design in bioequivalency assessment, pros and cons: bioavailabilities of the antidiabetic drugs pioglitazone and glimepiride present in a fixed-dose combination formulation.

    Science.gov (United States)

    Karim, Aziz; Zhao, Zhen; Slater, Margaret; Bradford, Dawn; Schuster, Jennifer; Laurent, Aziz

    2007-07-01

    An open-label, randomized, 2-sequence, 4-period crossover (7-day washout period between treatment), replicate design study was conducted in 37 healthy subjects to assess intersubject and intrasubject variabilities in the peak (Cmax) and total (AUC) exposures to 2 oral antidiabetic drugs, pioglitazone and glimepiride, after single doses of 30 mg pioglitazone and 4 mg glimepiride, given under fasted state, as commercial tablets coadministered or as a single fixed-dose combination tablet. Variabilities for AUC(infinity) for coadministered and fixed-dose combination treatments were similar: 16% to 19% (intra) and 23% to 25% (inter) for pioglitazone and 18% to 19% (intra) and 29% to 30% for glimepiride (inter, excluding 1 poor metabolizer). Fixed-dose combination/coadministered least squares mean ratios of >or=0.86 and the 90% confidence intervals of these ratios for pioglitazone and glimepiride of between 0.80 and 1.25 for Cmax, AUC(lqc), and AUC(infinity) met the bioequivalency standards. Gender analysis showed that women showed mean of 16% and 30% higher exposure than men for glimepiride (excluding 1 poor metabolizer) and pioglitazone, respectively. There was considerable overlapping in the AUC(infinity) values, making gender-dependent dosing unnecessary. Patients taking pioglitazone and glimepiride as cotherapy may replace their medication with a single fixed-dose combination tablet containing these 2 oral antidiabetic drugs.

  10. Venlafaxine's effects on healthy volunteers' driving, psychomotor, and vigilance performance during 15-day fixed and incremental dosing regimens.

    Science.gov (United States)

    O'Hanlon, J F; Robbe, H W; Vermeeren, A; van Leeuwen, C; Danjou, P E

    1998-06-01

    Effects of venlafaxine, an antidepressant acting by selective serotonin and norepinephrine reuptake inhibition with a potency ratio of 5:1, were assessed in a standardized, actual driving test, a battery of psychomotor tests (Critical Flicker/Fusion Frequency, Critical Tracking, Divided Attention), and a 45-minute vigilance test (Mackworth Clock). Thirty-seven healthy volunteers, 22 of whom completed the study, received venlafaxine in fixed (37.5 mg twice a day) and incremental (37.5-75 mg twice a day) doses as well as mianserin (10-20 mg three times a day) and placebo according to a 4-period (15 days each), double-blind, crossover design. Testing occurred on days 1 and 7 and after dose increments, on days 8 and 15. Plasma concentrations of venlafaxine and its active metabolite were measured on test days for confirming compliance. Venlafaxine had no significant effect on the primary driving parameter (standard deviation of lateral position) and failed to impair psychomotor performance. Mianserin profoundly and consistently impaired driving and psychomotor performance. However, both drugs significantly impaired vigilance performance. Maximal effects occurred on day 1 with mianserin and similarly on day 7 with venlafaxine in both series. The increment in venlafaxine's dose on day 8 did not increase this effect. The drug's selectively impairing effect on vigilance is shared by other "serotonergic" anxiolytics and antidepressants, suggesting that interference with 5-HT transmission reduces arousal in particularly monotonous tasks or environments. This study concludes that venlafaxine does not generally affect driving ability and should be safe for use by patients who drive.

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

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    Daniel G Wootton

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

  12. COMPARATIVE BIOAVAILABILITY OF A FIXED-DOSE COMBINATION TABLET OF OLMESARTAN MEDOXOMIL/HYDROCHLOROTHIAZIDE IN HEALTHY KOREAN VOLUNTEERS.

    Science.gov (United States)

    Zheng, Renhua; Hwang, Ho Min; Kim, Bo-Hyung

    2016-01-01

    Combination therapy with diuretics and angiotensin II type 1 (AT1) receptor antagonist is frequently recommended for the control of blood pressure in hypertensive patients. This study was targeted to compare pharmacokinetic profiles of a new generic fixed-dose combination (FDC) tablet of olmesartan medoxomil/hydrochlorothiazide 20/12.5 mg and a reference formulation of Olmetec Plus 20/12.5 mg tablets in healthy volunteers. The study design was a randomized sequence and two-way crossover study in healthy subjects. They were to be randomly assigned to either one of the two sequence groups; each subject sequentially received a single oral dose of reference and test tablet with 7-day washout period. Blood sample was collected at pre-dose and at 0.33, 0.67, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 h post-dose. The blood concentrations were analyzed by LC-MS/MS. Both of the 90% CI for the treatment ratios (test/reference) of C(max) and AUC(last) were to be in the range of 0.800-1.250 with regards to olmesartan medoxomil and hydrochlorothiazide; the geometric mean ratios (test/reference) for olmesartan C(max) and AUC(last) were 0.979 (90% CI, 0.934-1.027) and 0.992 (0.946-1.041), respectively, and those for hydrochlorothiazide C(max) and AUC(last) were 0.966 (0.975-1.110) and 0.999 (0.963-1.038), respectively. No serious adverse events were reported during the study. The generic formulation of olmesartan medoxomil/hydrochlorothiazide 20/12.5 mg tablet was bioequivalent with the reference formulation of Olmetec Plus 20/12.5 mg tablet in regards to the pharmacokinetic parameters of olmesartan medoxomil and hydrochlorothiazide. Clinical Research Information Service (CRIS) Registration Number: KCT0001025. (https://cris.nih.go.kr/ Mar 18, 2014)

  13. Safety and effectiveness of a fixed-dose combination of olmesartan, amlodipine, and hydrochlorothiazide in clinical practice

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    Bramlage P

    2014-12-01

    Full Text Available Peter Bramlage,1 Eva-Maria Fronk,2 Wolf-Peter Wolf,3 Rüdiger Smolnik,3 Gemma Sutton,1 Roland E Schmieder4 1Institut für Pharmakologie und präventive Medizin, Mahlow, Germany; 2Daiichi Sankyo Europe GmbH, Munich, Germany; 3Daiichi Sankyo Deutschland GmbH, Munich, Germany; 4Abteilung für Nephrologie und Hypertensiologie, Universitätsklinikum Erlangen, Erlangen, Germany Background: Clinical trials indicate that the use of fixed-dose combinations (FDCs is associated with a higher level of treatment adherence and prolonged blood pressure (BP control. The aim of this study was to document the safety and effectiveness of the FDC olmesartan/amlodipine/hydrochlorothiazide in patients with essential hypertension in clinical practice. Methods: This multicenter, prospective, 24-week, noninterventional study enrolled 5,831 patients from primary care offices in Germany and Austria. Inclusion criteria were a diagnosis of essential hypertension and newly initiated treatment with the FDC. Results: The mean age of patients was 63.5 years, almost 50% of patients had a time since diagnosis of essential hypertension of over 5 years, and approximately 70% of patients had at least one cardiovascular risk factor, including 29.4% of patients with diabetes mellitus. Following approximately 24 weeks of treatment, the mean reduction in systolic/diastolic BP was 29.0/14.0 mmHg, a BP response was observed by 94.2% of patients, and a target BP of <140/90 mmHg was attained in 67.5% of patients. At least one adverse drug reaction (ADR was experienced by 1.2% of patients, with the most common being peripheral edema. Subanalyses demonstrated that the following factors did not have a significant influence on the ADR rate: age (<65 years versus ≥65 years, diabetes mellitus (no/yes, cardiovascular risk (low/high, and concomitant medication (no/yes. Conclusion: This study demonstrates that in clinical practice, treatment with the three-drug combination as an FDC tablet

  14. Three in one: safety, efficacy, and patient acceptability of triple fixed-dose combination medicine in the management of hypertension

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    Taylor AA

    2012-08-01

    Full Text Available Addison A Taylor, Shawn RagbirDepartment of Medicine, Baylor College of Medicine, Houston, TX, USAAbstract: Hypertensive patients whose blood pressures are more than 20 mmHg above their goal will often require three or more medications. Careful selection of medications whose actions are complementary or have an improved adverse effect profile when combined can affect not only the blood pressure but also patient acceptance, thus improving persistence in taking the medications as prescribed. This review will highlight the three single-pill three-drug combinations currently available in the US and will address their efficacy, safety, and tolerability. All three include the dihydropyridine calcium-channel blocker, amlodipine, and the thiazide diuretic, hydrochlorothiazide. They each contain a different renin–angiotensin system blocker. One includes the angiotensin-receptor blocker, olmesartan, while another contains valsartan. The third combination includes the direct renin inhibitor, aliskiren. All three fixed-dose combinations (FDC at maximum doses of each component lowers the blood pressure of patients with stage II hypertension by 37 to 40 mmHg systolic and 21 to 25 mmHg diastolic, which is superior to any two of the components that comprise the three-drug FDC. These drugs are effective in males and females, the elderly, diabetics, minority populations, and patients with metabolic syndrome. Triple-drug FDCs are well tolerated with a low incidence of adverse effects, the most common being peripheral edema related to amlodipine. Extrapolation of data from two-drug FDC suggests that medication compliance (adherence and persistence should be better with these FDCs than with the individual components taken as separate medications, although additional studies are necessary to confirm this.Keywords: calcium-channel blockers, hypertension, patient tolerability, renin–angiotensin system antagonists, safety, triple-drug combinations

  15. Safety, Efficacy, and Bioavailability of Fixed-Dose Combinations in Type 2 Diabetes Mellitus: A Systematic Updated Review.

    Science.gov (United States)

    Vijayakumar, Thangavel Mahalingam; Jayram, Jayasutha; Meghana Cheekireddy, Vishnu; Himaja, Dasari; Dharma Teja, Yalamanchili; Narayanasamy, Damodharan

    2017-01-01

    Type 2 diabetes mellitus (T2DM) is a multifactorial disease characterized by insulin resistance. As time progresses, monotherapy often does not provide effective glycemic control, generating the need for an add-on therapy. Hence, multiple oral hypoglycemic agents formulated as a single-dose form called fixed-dose combinations (FDCs) play an essential role in glycemic control. The purpose of this systematic review is to appraise the recently published evidence on the safety, efficacy, and bioavailability of FDCs. A comprehensive literature search of PUBMED, Scopus, ScienceDirect.com, ProQuest, SpringerLink, clintrials.gov, Embase, and EBSCO using the key words FDCs, combination therapy, T2DM management, and add-on therapy was conducted. Studies on the safety profile/tolerability, efficacy, and bioavailability of various FDCs of oral hypoglycemic agents were preferred. The systematic review of all the publications suggests that FDCs of oral hypoglycemic agents (OHAs) significantly reduce HbA1c and fasting plasma glucose values, thereby efficiently reducing hyperglycemia in patients in whom monotherapy fails. FDCs are the bioequivalent of the concomitant drugs administered as individual components. Improved adherence to FDCs and the absence of serious adverse drug reactions compared with dual therapy play an important role in decreasing the incidence of hyperglycemia in patients with T2DM. From this updated review, it was found that metformin was the most widely used component of FDCs with other OHAs. Studies on the safety and efficacy of newly approved OHAs such as sodium glucose cotransporter inhibitors were limited. An increasing number of randomized trials on the safety and efficacy of newly emerging FDCs suggests that they would be better treatment options for T2DM patients.

  16. Pharmacokinetics of amlodipine and olmesartan after administration of amlodipine besylate and olmesartan medoxomil in separate dosage forms and as a fixed-dose combination.

    Science.gov (United States)

    Rohatagi, Shashank; Lee, James; Shenouda, Magdy; Haworth, Stephen; Bathala, Mohinder Singh; Allison, Mark; Rubets, Igor; Heyrman, Reinilde; Noveck, Robert; Salazar, Daniel E

    2008-11-01

    The pharmacokinetics of amlodipine and olmesartan in healthy volunteers after coadministration of amlodipine besylate and olmesartan medoxomil concomitantly as separate dosage forms and together in a fixed-dose combination tablet were characterized in 5 phase I, randomized, crossover studies. The mean steady-state pharmacokinetics of amlodipine and olmesartan were similar when olmesartan medoxomil 40 mg/day and amlodipine 10 mg/day were administered separately or concomitantly for 10 days. The total and maximum exposure to amlodipine and olmesartan after administration of fixed-dose combination amlodipine/olmesartan medoxomil 10 mg/40 mg was bioequivalent to amlodipine 10 mg plus olmesartan medoxomil 40 mg. The ratio of least squares mean and 90% confidence intervals for the area under the drug concentration-time curve from time zero to time t, from time zero to infinity, and the maximum observed plasma drug concentration of amlodipine and olmesartan fell within the prespecified range for bioequivalence (80.0% - 125.0%). The area under the drug concentration-time curve from time zero to time t, from time zero to infinity, and the maximum observed plasma drug concentration of both drugs also met the prespecified criterion for bioequivalence when the fixed-dose combination tablet was taken 30 minutes after a high-fat breakfast. Total exposure to amlodipine and olmesartan was dose-proportional after administration of olmesartan medoxomil 10 mg to 40 mg in the fixed-dose combination formulation with amlodipine 5 mg to 10 mg. From a pharmacokinetic perspective, the 2 drugs are well suited to coadministration in a fixed-dose combination.

  17. Evaluation of sofosbuvir, velpatasvir plus voxilaprevir as fixed-dose co-formulation for treating hepatitis C.

    Science.gov (United States)

    Soriano, Vicente; Benítez-Gutiérrez, Laura; Arias, Ana; Carrasco, Itziar; Barreiro, Pablo; Peña, Jose M; de Mendoza, Carmen

    2017-09-01

    The fixed-dose combination of three direct-acting antivirals (DAA), namely sofosbuvir, velpatasvir and voxilaprevir is the first pangenotypic, single tablet regimen developed for the treatment of HCV infection. Areas covered: The pharmacokinetics, pharmacodynamics, efficacy and safety of the co-formulation are reviewed. Information on drug absorption, distribution, metabolism and excretion of each of the three antivirals is evaluated. Finally, antiviral activity, safety and potential for drug interactions in phase II/III clinical trials in distinct patient populations are discussed. Expert opinion: The triple co-formulation of sofosbuvir-velpatasvir-voxilaprevir represents a major step towards HCV eradication. It depicts high efficacy even in patients infected with viruses harboring resistance-associated substitutions (RAS), including those selected after DAA failures. Likewise, very high success rates and good tolerance are seen in special patient populations, including decompensated cirrhotics, HIV coinfection, organ transplantation or renal insufficiency. A pill once daily for 8 weeks gives SVR rates above 95%. In prior DAA failures, extending treatment to 12 weeks maximizes SVR rates.

  18. Calendering as a direct shaping tool for the continuous production of fixed-dose combination products via co-extrusion.

    Science.gov (United States)

    Vynckier, A-K; Lin, H; Zeitler, J A; Willart, J-F; Bongaers, E; Voorspoels, J; Remon, J P; Vervaet, C

    2015-10-01

    In this study calendering is used as a downstream technique to shape monolithic co-extruded fixed-dose combination products in a continuous way. Co-extrudates with a metoprolol tartrate-loaded sustained-release core and a hydrochlorothiazide-loaded immediate-release coat were produced and immediately shaped into a monolithic drug delivery system via calendering, using chilled rolls with tablet-shaped cavities. In vitro metoprolol tartrate release from the ethylcellulose core of the calendered tablets was prolonged in comparison with the sustained release of a multiparticulate dosage form, prepared manually by cutting co-extrudates into mini-matrices. Analysis of the dosage forms using X-ray micro-computed tomography only detected small differences between the pore structure of the core of the calendered tablet and the mini-matrices. Diffusion path length was shown to be the main mechanism behind the release kinetics. Terahertz pulsed imaging visualized that adhesion between the core and coat of the calendered tablet was not complete and a gradient in coat thickness (varying from 200 to 600μm) was observed. Modulated differential scanning calorimetry and X-ray diffraction indicated that the solid-state properties of both drugs were not affected by the calendering procedure.

  19. 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

    2016-01-01

    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.

  20. Zero crossing and ratio spectra derivative spectrophotometry for the dissolution tests of amlodipine and perindopril in their fixed dose formulations

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    Maczka Paulina

    2014-06-01

    Full Text Available Dissolution tests of amlodipine and perindopril from their fixed dose formulations were performed in 900 mL of phosphate buffer of pH 5.5 at 37°C using the paddle apparatus. Then, two simple and rapid derivative spectrophotometric methods were used for the quantitative measurements of amlodipine and perindopril. The first method was zero crossing first derivative spectrophotometry in which measuring of amplitudes at 253 nm for amlodipine and 229 nm for perindopril were used. The second method was ratio derivative spectrophotometry in which spectra of amlodipine over the linearity range were divided by one selected standard spectrum of perindopril and then amplitudes at 242 nm were measured. Similarly, spectra of perindopril were divided by one selected standard spectrum of amlodipine and then amplitudes at 298 nm were measured. Both of the methods were validated to meet official requirements and were demonstrated to be selective, precise and accurate. Since there is no official monograph for these drugs in binary formulations, the dissolution tests and quantification procedure presented here can be used as a quality control test for amlodipine and perindopril in respective dosage forms.

  1. Accelerated Onset of Action and Increased Tolerability in Treating Acne With a Fixed-Dose Combination Gel.

    Science.gov (United States)

    Friedman, Adam; Waite, Kim; Brandt, Staci; Meckfessel, Matthew H

    2016-02-01

    Nonadherence to topical acne therapies is a major contributing factor to poor treatment outcomes. Multiple contributing factors have been identified, including a lack of perceived efficacy and fear of side effects. A fixed-dose combination gel of adapalene/benzoyl peroxide gel, 0.1%/2.5% (A-BPO) is an efficacious and safe treatment for a range of acne severities in patients as young as 9 years old. A meta-analysis of 14 clinical studies involving A-BPO was conducted to assess the 4 week efficacy and overall tolerability of this treatment. Over 2,300 subjects were included in the analysis. Mean total, inflammatory, and non-inflammatory lesion counts decreased at 4 weeks by 40.8%, 46.2%, and 37.5%, respectively. Worst post-baseline tolerability scores for stinging/burning, dryness, scaling, and erythema were none or mild for a majority of subjects. The result of this meta-analysis add to the body of literature supporting the use of A-BPO in a variety of acne patients and shows that A-BPO provides meaningful clinical results within 4 weeks and will be well-tolerated for a majority of patients. With a demonstrable quick onset of action and high tolerability, A-BPO may improve adherence, and ultimately treatment outcomes, by addressing factors that contribute to nonadherence.

  2. Impact of Fixed-Dose Combination of Germacrone,Curdione, and Furanodiene on Breast Cancer Cell Proliferation

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    Qi Kong

    2013-01-01

    Full Text Available Objective: Herb combination has been very popular in traditional medical prescriptions such as Traditional Chinese Medicine (TCM. Persistent efforts and attempts have been made to dissect the action mode of TCM in recent years, which has provided certain evidence for inter-herbal interactions. However, the interactions among different components in a single herb have been largely neglected.Materials and Methods: In this experimental study, the interactions among different components of a single herb were explored. The effect of three main sesquiterpenes (germacrone, curdione, furanodiene isolated from Curcuma WenyujinY.H.Chenet C Ling on MDA-MB-231 and MCF-7 breast cancer cell proliferation alone or in combination with a fixed-dose-combination was investigated.Results: Furanodiene significantly inhibited cancer cell proliferation while germacrone and curdione showed no effect. Germacrone enhanced furanodiene’s anti-proliferative effect. Curdione showed no effect on furanodiene’s anti-proliferative effect but partly reversed the anti-proliferative effect of germacrone and furanodiene combined. The morphological and mitochondrial membrane potential (Δψm changes showed similar results. However, they demonstrated complicated interactions on the expression of apoptotic-related proteins and key signal transduction proteins.Conclusion: Unpredictable and complex interactions among different components in Curcuma WenyujinY.H.Chenet C Ling may exist. The intra-herb interactions should be taken into consideration when attempts are made to interpret the art of TCM formulation or other similar recipes.

  3. Profile of once-daily darunavir/cobicistat fixed-dose combination for the treatment of HIV/AIDS

    Science.gov (United States)

    Navarro, Jordi; Curran, Adrian

    2016-01-01

    Efficacy is the main objective of antiretroviral treatment and adherence is one of the cornerstones to achieve it. For this reason, treatment simplification is of key importance with regard to antiretroviral regimens. Rezolsta® (darunavir/cobicistat) is the first fixed-dose combination containing a protease inhibitor approved for HIV treatment. This coformulation includes darunavir, a protease inhibitor that has shown its efficacy and safety in naïve and treatment-experienced patients, and cobicistat, the new pharmacokinetic enhancer that is expected to replace ritonavir. Bioequivalence between ritonavir and cobicistat as darunavir boosters has been shown in studies involving healthy volunteers. Furthermore, efficacy and safety of darunavir/cobicistat observed in phase III studies, including naïve and pretreated patients without darunavir-associated resistance mutations, are comparable to historical data of darunavir/ritonavir 800/100 mg once-daily formulation. Adverse events with darunavir/cobicistat are scarce and mild, and basically include skin reactions and gastrointestinal disturbances. Although small increases in plasma creatinine are expected in patients receiving cobicistat due to the inhibition of creatinine transporters in kidney tubules, actual glomerular filtrate rate remains unaltered. Cobicistat does not have an inducer effect on metabolic pathways and shows much more selective inhibition than ritonavir. Therefore, isoenzyms different from CYP3A4 are supposed to be less affected by cobicistat, and thus fewer drug–drug interactions are expected. PMID:27843352

  4. Safety and effectiveness of a fixed-dose combination of olmesartan, amlodipine, and hydrochlorothiazide in clinical practice.

    Science.gov (United States)

    Bramlage, Peter; Fronk, Eva-Maria; Wolf, Wolf-Peter; Smolnik, Rüdiger; Sutton, Gemma; Schmieder, Roland E

    2015-01-01

    Clinical trials indicate that the use of fixed-dose combinations (FDCs) is associated with a higher level of treatment adherence and prolonged blood pressure (BP) control. The aim of this study was to document the safety and effectiveness of the FDC olmesartan/amlodipine/hydrochlorothiazide in patients with essential hypertension in clinical practice. This multicenter, prospective, 24-week, noninterventional study enrolled 5,831 patients from primary care offices in Germany and Austria. Inclusion criteria were a diagnosis of essential hypertension and newly initiated treatment with the FDC. The mean age of patients was 63.5 years, almost 50% of patients had a time since diagnosis of essential hypertension of over 5 years, and approximately 70% of patients had at least one cardiovascular risk factor, including 29.4% of patients with diabetes mellitus. Following approximately 24 weeks of treatment, the mean reduction in systolic/diastolic BP was 29.0/14.0 mmHg, a BP response was observed by 94.2% of patients, and a target BP of risk (low/high), and concomitant medication (no/yes). This study demonstrates that in clinical practice, treatment with the three-drug combination as an FDC tablet resulted in a very high proportion of patients with a BP response and control, accompanied by a very low rate of ADRs.

  5. Estimated cardiovascular relative risk reduction from fixed-dose combination pill (polypill) treatment in a wide range of patients with a moderate risk of cardiovascular disease

    NARCIS (Netherlands)

    Lafeber, Melvin; Webster, Ruth; Visseren, Frank L J; Bots, Michiel L.; Grobbee, Diederick E.; Spiering, W.; Rodgers, Anthony

    2016-01-01

    Aims Recent data indicate that fixed-dose combination (FDC) pills, polypills, can produce sizeable risk factor reductions. There are very few published data on the consistency of the effects of a polypill in different patient populations. It is unclear for example whether the effects of the polypill

  6. 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

    (salmeterol/fluticasone twice daily), once-daily fixed-dose indacaterol/glycopyrronium has clinically important effects on symptoms, including dyspnea score, health status, level of lung function, and rate of moderate or severe exacerbations in patients with moderate-to-very severe COPD (Global initiative...

  7. Cost-effectiveness and budget impact of the fixed-dose dual bronchodilator combination tiotropium–olodaterol for patients with COPD in the Netherlands

    NARCIS (Netherlands)

    van Boven, Job Fm; Kocks, Janwillem Wh; Postma, Maarten J

    2016-01-01

    PURPOSE: The fixed-dose dual bronchodilator combination (FDC) of tiotropium and olodaterol showed increased effectiveness regarding lung function and health-related quality of life in patients with chronic obstructive pulmonary disease (COPD) compared with the use of its mono-components. Yet, while

  8. Cost-effectiveness and budget impact of the fixed-dose dual bronchodilator combination tiotropium–olodaterol for patients with COPD in the Netherlands

    NARCIS (Netherlands)

    Van Boven, Job F. M.; Kocks, Janwillem W. H.; Postma, Maarten J.

    2016-01-01

    Purpose: The fixed-dose dual bronchodilator combination (FDC) of tiotropium and olodaterol showed increased effectiveness regarding lung function and health-related quality of life in patients with chronic obstructive pulmonary disease (COPD) compared with the use of its mono-components. Yet, while

  9. Repeated treatment of recurrent uncomplicated Plasmodium falciparum malaria in Senegal with fixed-dose artesunate plus amodiaquine versus fixed-dose artemether plus lumefantrine: a randomized, open-label trial

    Directory of Open Access Journals (Sweden)

    Barry Aichatou

    2011-08-01

    Full Text Available Abstract Background The use of artemisinin-based combination therapy (ACT is currently recommended for treating uncomplicated malaria. The objective was to assess the efficacy and safety of repeated administrations of two fixed-dose presentations of ACT - artesunate plus amodiaquine (ASAQ and artemether-lumefantrine (AL - in subsequent episodes of Plasmodium falciparum malaria. Methods A randomized comparative study was conducted in a rural community of central Senegal from August 2007 to January 2009. Children and adults with uncomplicated P. falciparum malaria were randomized to receive open-label ASAQ once daily or AL twice daily for three days. Drug doses were given according to body weight. Treatments for first episodes were supervised. For subsequent episodes, only the first intake of study drug was supervised. ECGs and audiograms were performed in patients ≥12 years of age. Primary outcome was adequate clinical and parasitological response rate (ACPR after polymerase chain reaction (PCR correction on day 28 for the first episode. Results A total of 366 patients were enrolled in the two groups (ASAQ 184, AL 182 and followed up during two malaria transmission seasons. In the intent-to-treat population, PCR-corrected ACPRs at day 28 for the first episode were 98.4% and 96.2%, respectively, in the ASAQ and AL groups. For the per-protocol population (ASAQ 183, AL 182, PCR-corrected ACPRs at day 28 for the first episode were 98.9% and 96.7%, respectively. A 100% ACPR rate was obtained at day 28 in the 60 and four patients, respectively, who experienced second and third episodes. Treatment-related adverse events were reported in 11.7% of the patients, without significant differences between the two groups. A better improvement of haemoglobin at day 28 was noted in the ASAQ versus the AL group (12.2 versus 11.8 g/dL; p = 0.03. No sign of ototoxicity was demonstrated. A prolongation of the QTc interval was observed in both groups during

  10. Bioequivalence evaluation of two amlodipine salts, besylate and orotate, each in a fixed-dose combination with olmesartan in healthy subjects.

    Science.gov (United States)

    Lee, Soo-Yun; Kim, Jung-Ryul; Jung, Jin Ah; Huh, Wooseong; Bahng, Mi Young; Ko, Jae-Wook

    2015-01-01

    A fixed-dose combination of amlodipine and olmesartan is used to treat high blood pressure in patients whose hypertension is not sufficiently controlled with either drug alone. The objective of this study was to evaluate the bioequivalence of two fixed-dose combinations, ie, amlodipine orotate/olmesartan medoxomil 10/40 mg and amlodipine besylate/olmesartan medoxomil 10/40 mg, in healthy subjects. A randomized, open-label, single-dose, two-sequence, two-period, crossover study was conducted in 30 healthy adult volunteers. Blood samples were collected for up to 72 hours post-dose in each period. Safety data included the results of physical examinations, clinical laboratory tests, vital signs, an electrocardiogram, and adverse events. For both amlodipine and olmesartan, the 90% confidence intervals for the geometric mean ratios of AUClast and time to peak plasma concentration fell within the bioequivalence acceptance criteria. The two fixed-dose combinations showed similar safety profiles. Amlodipine orotate/olmesartan medoxomil 10/40 mg was bioequivalent to amlodipine besylate/olmesartan medoxomil 10/40 mg.

  11. Comparative effect of fixed dose combination of Amlodipine + Bisoprolol versus Amlodipine and Bisoprolol alone on blood pressure in stage-2 essential hypertensive patients.

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    Shirure PA,Tadvi NA, Bajait CS, Baig MS, Gade PR

    2012-09-01

    Full Text Available Background: Employment of low dose combinations of two antihypertensives, with different mode of action has gained acceptance worldwide for the treatment of mild to moderate hypertension. However, most studies in hypertensive disease have focused on monotherapy. The combination therapy in the treatment of hypertension is largely extrapolated from these monotherapy studies. Objectives: To study and compare the effect of amlodipine, bisoprolol and fixed dose combination of amlodipine + bisoprolol on blood pressure in stage-2 essential hypertensive patients. Methods: The present study was carried out in Department of Pharmacology in collaboration with Department of Medicine at Government Medical College and Hospital, Aurangabad. Results and Conclusion : Amlodipine + bisoprolol in fixed dose combination have showed significant blood pressure control in patients of stage-2 essential hypertension and the antihypertensive effect was greater than individual monotherapy study groups.

  12. Bioequivalence evaluation of two amlodipine salts, besylate and orotate, each in a fixed-dose combination with olmesartan in healthy subjects

    Directory of Open Access Journals (Sweden)

    Lee SY

    2015-06-01

    Full Text Available Soo-Yun Lee,1 Jung-Ryul Kim,2,3 Jin Ah Jung,4 Wooseong Huh,2,5 Mi Young Bahng,6 Jae-Wook Ko1,2 1Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea; 2Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, Seoul, Republic of Korea; 3Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea; 4Department of Clinical Pharmacology, Inje University, Busan Paik Hospital, Busan, Republic of Korea; 5Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; 6Dong-A ST Co., Ltd., Seoul, Republic of Korea Abstract: A fixed-dose combination of amlodipine and olmesartan is used to treat high blood pressure in patients whose hypertension is not sufficiently controlled with either drug alone. The objective of this study was to evaluate the bioequivalence of two fixed-dose combinations, ie, amlodipine orotate/olmesartan medoxomil 10/40 mg and amlodipine besylate/olmesartan medoxomil 10/40 mg, in healthy subjects. A randomized, open-label, single-dose, two-sequence, two-period, crossover study was conducted in 30 healthy adult volunteers. Blood samples were collected for up to 72 hours post-dose in each period. Safety data included the results of physical examinations, clinical laboratory tests, vital signs, an electrocardiogram, and adverse events. For both amlodipine and olmesartan, the 90% confidence intervals for the geometric mean ratios of AUClast and time to peak plasma concentration fell within the bioequivalence acceptance criteria. The two fixed-dose combinations showed similar safety profiles. Amlodipine orotate/olmesartan medoxomil 10/40 mg was bioequivalent to amlodipine besylate/olmesartan medoxomil 10/40 mg. Keywords: amlodipine orotate, amlodipine besylate, olmesartan medoxomil, fixed-dose combination, bioequivalence

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

    Directory of Open Access Journals (Sweden)

    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

  14. Fixed-Dose Combination of Canagliflozin and Metformin for the Treatment of Type 2 Diabetes: An Overview.

    Science.gov (United States)

    Davidson, Jaime A; Sloan, Lance

    2017-01-01

    Metformin is recommended as a first-line therapy for patients with type 2 diabetes mellitus (T2DM). However, many patients do not achieve glycemic goals with metformin monotherapy and require subsequent combination therapy with other antihyperglycemic agents (AHAs). For newly diagnosed patients with high blood glucose, initial combination therapy may be required to achieve glycemic control. The American Association for Clinical Endocrinologists algorithm for the treatment of T2DM recommends metformin plus a sodium glucose co-transporter 2 (SGLT2) inhibitor as the first oral combination in patients who present with HbA1c ≥7.5%. Canagliflozin, an SGLT2 inhibitor, lowers the renal threshold for glucose and increases urinary glucose excretion leading to a mild osmotic diuresis and a net caloric loss. The effect of canagliflozin is insulin-independent and complementary to other AHAs, including metformin. A fixed-dose combination (FDC) of canagliflozin and metformin is also available with variable dosing, which may be attractive to some patients owing to the potential for reduced pill burden and costs. This article reviews the efficacy and safety of canagliflozin in combination with metformin based on data from the canagliflozin phase 3 clinical program. As initial combination therapy in drug-naïve patients or as dual therapy with metformin or triple therapy in combination with metformin and other AHAs, canagliflozin 100 and 300 mg improved glycemic control and provided reductions in body weight and systolic blood pressure that were sustained for up to 104 weeks. Canagliflozin was generally well tolerated across studies in combination with metformin. An increased incidence of adverse events (AEs) related to the mechanism of SGLT2 inhibition (i.e., genital mycotic infections, urinary tract infections, osmotic diuresis-related AEs) was observed with canagliflozin. Canagliflozin was associated with a low incidence of hypoglycemia when not used in conjunction with AHAs

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

    Science.gov (United States)

    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

  16. Relative Bioavailability of Rifampicin in Four Chinese Fixed-dose Combinations Compared with Rifampicin in Free Combinations

    Institute of Scientific and Technical Information of China (English)

    Hui Zhu; Shao-Chen Guo; Lan-Hu Hao; Cheng-Cheng Liu; Bin Wang; Lei Fu; Ming-Ting Chen

    2015-01-01

    Background:Decreases in the bioavailability of rifampicin (RFP) can lead to the development of drug resistance and treatment failure.Therefore,we investigated the relative bioavailability of RFP from one four-drug fixed-dose combination (FDC; formulation A) and three two-drug FDCs (formulations B,C,and D) used in China,compared with RFP in free combinations of these drugs (reference),in healthy volunteers.Methods:Eighteen and twenty healthy Chinese male volunteers participated in two open-label,randomized two-period crossover (formulations A and C) or one three-period crossover (formulations B and D) study,respectively.The washout period between treatments was 7 days.Bioequivalence was assessed based on 90% confidence intervals,according to two one-sided t-tests.All analyses were done with DAS 3.1.5 (Mathematical Pharmacology Professional Committee of China,Shanghai,China).Results:Mean pharmacokinetic parameter values of RFP obtained for formulations A,B,C,and D products were 11.42 ± 3.41 μg/ml,7.86 ± 5.78 μg/ml,13.05 ± 6.80 μg/ml,and 16.18 ± 3.87 μg/ml,respectively,for peak plasma concentration (Cmax),91.43± 30.82 μg·h-1 ·ml-1,55.49 ± 37.58 μg·h-1·ml-1,96.50 ± 47.24 μg·h-1·ml-1,101.47 ± 33.07 μg·h-1·ml-1,respectively,for area under the concentration-time curve (AUC0-2,4 h).Conclusions:Although the concentrations of RFP for formulations A,C,and D were within the reported acceptable therapeutic range,only formulation A was bioequivalent to the reference product.The three two-drug FDCs (formulations B,C and D) displayed inferior RFP bioavailability compared with the reference (Chinese Clinical Trials registration number:ChiCTR-TTRCC-12002451).

  17. The irrational fixed dose combinations in the Indian drug market: an evaluation of prescribing pattern using WHO guidelines

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    Somesh P. Rayasam

    2013-08-01

    Full Text Available Background: Evaluation of the pattern of fixed dose combinations (FDCs prescribing amongst the practitioners in a tertiary care hospital in Central India. Methods: Nine hundred and ninety four prescriptions, containing 639 FDCs were scrutinized in the tertiary care hospital. After excluding the total and the interdepartmental repetitions, the numbers of FDCs were 278, which were considered for final analysis. Inclusion criteria were FDCs from the major out-patient department (OPD of the tertiary care hospital from January 2011 to December 2011. FDCs from the wards, casualty, infectious disease unit, intensive cardiac care unit (ICCU, tuberculosis and chest and HIV unit were excluded from the study. FDCs were analysed for the different pattern of prescribing and rationalism. Results were expressed as percentages. Results: Out of 639 FDCs, the most commonly prescribed FDCs were B complex (12.20%, pantoprazole plus domperidone (9.55% and amoxicillin plus clavulanic acid (7.35%. Seventy percent of the FDCs were prescribed to the age group of 21-60 years. The FDCs were maximum from the department of medicine (25.59%, followed by surgery (15.47% and ENT 13.69%. Out of 278 FDCs, only 5.4% were rational, and rest of the FDCs were irrational. Ninety five percent of all FDCs were brand names. The physicians were unaware of the active pharmacological ingredients (APIs of 20.86% FDCs. Ninety two percent FDCs were available as over the counter (OTCs. Forty eight percent FDCs were costing from Rs. 0-50. There were 2.87% FDCs whose price was above Rs. 500. Conclusions: Irrational FDCs are prescribed by all the departments. Physicians were ignorant about the essential drugs and FDCs. Patients didn’t have access to rational medicines. Therefore, physicians and regulators should be alerted in time. Regulatory actions or government laws should be made mandatory. Availability and access to 348 essential medicines for basic health care should be the priority of the

  18. A fixed-dose 24-hour regimen of artesunate plus sulfamethoxypyrazine-pyrimethamine for the treatment of uncomplicated Plasmodium falciparum malaria in eastern Sudan

    DEFF Research Database (Denmark)

    Adam, Ishag; Magzoub, Mamoun; Osman, Maha E

    2006-01-01

    -sulfamethoxypyrazine-pyrimethamine (AS+SMP f) administered at time intervals of 12 hours for a 24-hour therapy was compared with the efficacy of the same drug given as a loose combination (AS+SMP l) with a dose interval of 24 hours for 3 days for the treatment of uncomplicated Plasmodium falciparum malaria in eastern Sudan. RESULTS...... of the patients. CONCLUSION: both regimens of AS+SMP were effective and safe for the treatment of uncomplicated P. falciparum malaria in eastern Sudan. Due to its simplicity, the fixed dose one-day treatment regimen may improve compliance and therefore may be the preferred choice....

  19. Fixed combination of benazepril and low-dose amlodipine in the treatment of mild to moderate essential hypertension: evaluation by 24-hour noninvasive ambulatory blood pressure monitoring.

    Science.gov (United States)

    Fogari, R; Zoppi, A; Lusardi, P; Mugellini, A; Preti, P; Motolese, M

    1997-08-01

    The antihypertensive efficacy and tolerability of a fixed combination of benazepril (10 mg) and low-dose amlodipine (2.5 mg) were assessed in 24 patients (mean age, 43.9 years) with uncomplicated mild to moderate essential hypertension [supine diastolic blood pressure (DBP) > or = 95 and benazepril 10 mg/amlodipine 2.5 mg was well tolerated, and no patient withdrew from the study because of side effects.

  20. 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

    Energy Technology Data Exchange (ETDEWEB)

    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)

  1. 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

    Directory of Open Access Journals (Sweden)

    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.

  2. The efficacy and safety of a new fixed-dose combination of amodiaquine and artesunate in young African children with acute uncomplicated Plasmodium falciparum

    Directory of Open Access Journals (Sweden)

    Kiechel Jean

    2009-03-01

    Full Text Available Abstract Background Artesunate (AS plus amodiaquine (AQ is one artemisinin-based combination (ACT recommended by the WHO for treating Plasmodium falciparum malaria. Fixed-dose AS/AQ is new, but its safety and efficacy are hitherto untested. Methods A randomized, open-label trial was conducted comparing the efficacy (non-inferiority design and safety of fixed (F dose AS (25 mg/AQ (67.5 mg to loose (L AS (50 mg + AQ (153 mg in 750, P. falciparum-infected children from Burkina Faso aged 6 months to 5 years. Dosing was by age. Primary efficacy endpoint was Day (D 28, PCR-corrected, parasitological cure rate. Recipients of rescue treatment were counted as failures and new infections as cured. Documented, common toxicity criteria (CTC graded adverse events (AEs defined safety. Results Recruited and evaluable children numbered 750 (375/arm and 682 (90.9%, respectively. There were 8 (AS/AQ and 6 (AS+AQ early treatment failures and one D7 failure (AS+AQ. Sixteen (AS/AQ and 12 (AS+AQ patients had recurrent parasitaemia (PCR new infections 10 and 6, respectively. Fourteen patients per arm required rescue treatment for vomiting/spitting out study drugs. Efficacy rates were 92.1% in both arms: AS/AQ = 315/342 (95% CI: 88.7–94.7 vs. AS+AQ = 313/340 (95% CI: 88.6–94.7. Non-inferiority was demonstrated at two-sided α = 0.05: Δ (AS+AQ – AS/AQ = 0.0% (95% CI: -4.1% to 4.0%. D28, Kaplan Meier PCR-corrected cure rates (all randomized children were similar: 93.7% (AS/AQ vs. 93.2% (AS+AQ Δ = -0.5 (95% CI -4.2 to 3.0%. By D2, both arms had rapid parasite (F & L, 97.8% aparasitaemic and fever (97.2% [F], 96.0% [L] afebrile clearances. Both treatments were well tolerated. Drug-induced vomiting numbered 8/375 (2.1% and 6/375 (1.6% in the fixed and loose arms, respectively (p = 0.59. One patient developed asymptomatic, CTC grade 4 hepatitis (AST 1052, ALT 936. Technical difficulties precluded the assessment and risk of neutropaenia for all patients. Conclusion

  3. New Fixed-Dose Artesunate-Mefloquine Formulation against Multidrug-Resistant Plasmodium falciparum in Adults: a Comparative Phase IIb Safety and Pharmacokinetic Study with Standard-Dose Nonfixed Artesunate plus Mefloquine▿

    Science.gov (United States)

    Krudsood, S.; Looareesuwan, S.; Tangpukdee, N.; Wilairatana, P.; Phumratanaprapin, W.; Leowattana, W.; Chalermrut, K.; Ramanathan, S.; Navaratnam, V.; Olliaro, P.; Vaillant, M.; Kiechel, J. R.; Taylor, W. R. J.

    2010-01-01

    A new fixed-dose artesunate (AS)-mefloquine (MQ) was assessed in adults hospitalized for 28 days with uncomplicated drug-resistant falciparum malaria. The patients (n = 25/arm) were treated with (i) two fixed-dose tablets (AS-MQ arm; 100 mg AS-200 mg MQ/tablet) daily for 3 days (days 0, 1, and 2) or (ii) nonfixed AS (AS-plus-MQ arm; 4 mg/kg of body weight/day for 3 days) plus MQ (15 mg/kg on day 1 and 10 mg/kg on day 2), dosed by weight. Clinical laboratory electrocardiogram (ECG), adverse events (AEs), efficacy, and pharmacokinetic parameters were assessed over 28 days. Both regimens were well tolerated. No AEs were drug related. Two serious AEs of malaria-induced hypotension occurring in the AS-MQ arm necessitated rescue treatment. There were no significant changes in hematology, biochemistry, or PR and QRS intervals. For all patients, mean Fridericia-corrected QT intervals were significantly (P ≤ 0.0027) prolonged on day 3 (407 ms) and day 7 (399 ms) versus day 0 (389 ms), in parallel with significant (P ≤ 0.0003) falls in heart rates (67 [day 3], 73 [day 7], and 83 [day 0] beats/minute). Fixed-nonfixed formulations were bioequivalent for MQ, but not for AS and dihydroartemisinin (DHA). One AS-MQ patient developed a new infection on day 28; his day 28 plasma MQ concentration was 503.8 ng/ml. Fixed-dose AS-MQ was well tolerated, had pharmacokinetic (PK) profiles broadly similar to those of nonfixed AS plus MQ, and is a suitable replacement. PMID:20547795

  4. A phase I study of 153Sm-EDTMP with fixed high-dose melphalan as a peripheral blood stem cell conditioning regimen in patients with multiple myeloma.

    Science.gov (United States)

    Dispenzieri, A; Wiseman, G A; Lacy, M Q; Litzow, M R; Anderson, P M; Gastineau, D A; Tefferi, A; Inwards, D J; Micallef, I N M; Ansell, S M; Porrata, L; Elliott, M A; Lust, J A; Greipp, P R; Rajkumar, S V; Fonseca, R; Witzig, T E; Erlichman, C; Sloan, J A; Gertz, M A

    2005-01-01

    Despite response rates of 30% after high-dose chemotherapy with autologous hematopoietic stem cell transplant, patients with multiple myeloma are not cured. 153Samarium ethylenediaminetetramethylenephosphonate (153Sm-EDTMP; Quadramet) is a short-range, beta-emitting therapeutic radiopharmaceutical with avid skeletal uptake. In total, 12 patients were treated with escalating doses of 153Sm-EDTMP (N=3/group; 6, 12, 19.8, and 30 mCi/kg) and a fixed dose of melphalan (200 mg/m(2)). No dose limiting toxicity was seen. To better standardize the marrow compartment radiation dose, the study was modified such that an additional six patients were treated at a targeted absorbed radiation dose to the red marrow of 40 Gy based on a trace labeled infusion 1 week prior to the therapy. Despite rapid elimination of unbound radiopharmaceutical via kidneys and bladder, no episodes of nephrotoxicity, hemorrhagic cystitis, or delayed radiation nephritis were observed with a median follow-up of 31 months (range 8.5-44). Median times to ANC>0.5 and platelet >20 x 10(6)/l were 12 and 11 days, respectively, with no graft failures. Overall response rate was 94% including seven very good partial responses and five complete responses. Addition of 153Sm EDTMP to melphalan conditioning appears to be safe, well-tolerated and worthy of further study.

  5. Adjustable Maintenance Dosing with Budesonide/Formoterol Reduces Asthma Exacerbations Compared with Traditional Fixed Dosing: A Five-Month Multicentre Canadian Study

    Directory of Open Access Journals (Sweden)

    J Mark FitzGerlad

    2003-01-01

    Full Text Available BACKGROUND: Adjustable maintenance dosing with budesonide/formoterol in a single inhaler (Symbicort, AstraZeneca, Lund, Sweden may provide a convenient means of maintaining asthma control with the minimum effective medication level.

  6. Efficacy and safety of benzalkonium chloride-free fixed-dose combination of latanoprost and timolol in patients with open-angle glaucoma or ocular hypertension

    Directory of Open Access Journals (Sweden)

    Bhagat P

    2014-06-01

    Full Text Available Purvi Bhagat,1 Kalyani Sodimalla,2 Chandrima Paul,3 Surinder S Pandav,4 Ganesh V Raman,5 Rengappa Ramakrishnan,6 Abhijeet Joshi,7 Atul Raut7 1Glaucoma Clinic, M & J Western Regional Institute of Ophthalmology, Civil Hospital, Ahmedabad, Gujarat, India; 2Glaucoma Department, PBMA’s H.V. Desai Eye Hospital, Maharashtra, India; 3Glaucoma Service, B B Eye Foundation, Kolkata, India; 4Advanced Eye Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India; 5Glaucoma Clinic, Aravind Eye Hospital, Coimbatore, Tamilnadu, India; 6Glaucoma Clinic, Aravind Eye Hospital, Tirunelveli, Tamilnadu, India; 7Clinical Research Department, Sun Pharma Advanced Research Company Ltd, Mumbai, Maharashtra, India Background: Benzalkonium chloride (BAK is a common preservative in topical ocular preparations; however, prolonged use may lead to deleterious effects on the ocular surface, affecting quality of life and reducing adherence to treatment and overall outcomes. This study compared the intraocular pressure (IOP-lowering efficacy and safety of a novel once-daily, BAK-free, fixed-dose combination of latanoprost plus timolol with latanoprost or timolol administered as monotherapy or concomitantly. Methods: This was a 6-week, randomized, open-label, parallel-group, active-controlled study in patients aged ≥18 years with open-angle glaucoma or ocular hypertension. A total of 227 patients were randomized to either a once-daily, BAK-free, fixed-dose combination of latanoprost 0.005%/timolol 0.5% ophthalmic solution or concomitant administration of once-daily latanoprost 0.005% plus twice-daily timolol 0.5% or once-daily latanoprost 0.005% monotherapy, or twice-daily timolol 0.5% monotherapy. Efficacy end points were assessed at three time points on visits at weeks 1, 2, 4, and 6 versus baseline. Results: The IOP-lowering efficacy of the fixed-dose combination of latanoprost/timolol was similar to that of latanoprost plus timolol administered

  7. Predictive value of pyramidal lobe, percentage thyroid uptake and age for ablation outcome after 15 mCi fixed dose of radioiodine-131 in Graves’ disease

    Science.gov (United States)

    Zaman, Maseeh uz; Fatima, Nosheen; Zaman, Unaiza; Sajjad, Zafar; Zaman, Areeba; Tahseen, Rabia

    2015-01-01

    Purpose: The purpose was to find out the efficacy of fixed 15 mCi radioactive iodine-131 (RAI) dose and predictive values of various factors for inducing hypothyroidism in Graves’ disease (GD). Materials and Methods: Retrospective study conducted from January 2012 till August 2014. Patients with GD who had a technetium-99m thyroid scan, thyroid antibodies, received fixed 15 mCi RAI and did follow endocrine clinics for at least 6 months were selected. RAI was considered successful if within 6 months of RAI therapy patients developed hypothyroidism. Results: Of the 370 patients with GD who had RAI during study period, 210 (57%) qualified study criteria. Mean age of patients was 48 ± 15 years with female: male ratio of 69:31, positive thyroid antibodies in 61%, means thyroid uptake of 15.09 ± 11.23%, and presence of pyramidal lobe in 40% of total population. Hypothyroidism was achieved in 161 (77%) patients while 49 (23%) patients failed to achieve it (remained either hyperthyroid or euthyroid on antithyroid medication). Patients who became hypothyroid were significantly younger with higher proportion of presence of thyroid antibodies and pyramidal lobe and lower percentage thyroid uptake than those who failed. Multiple logistic regression analysis revealed that age (odds ratio; OR = 2.074), pyramidal lobe (OR = 3.317), thyroid antibodies (OR = 8.198), and percentage thyroid uptake (OR = 3.043) were found to be significant prognostic risk factors for post-RAI hypothyroidism. Gender was found to have nonsignificant association with the development of hypothyroidism. Receiver operating characteristic analysis revealed age <42 years and thyroid uptake <15% as threshold values for the development of post-RAI hypothyroidism. Conclusion: We conclude that fixed (15 mCi) RAI dose is highly effective in rendering hypothyroidism in patients with GD. Age (≤42 years), thyroid uptake (≤15%) and presence of pyramidal lobe are strong predictors of hypothyroidism and must be

  8. Randomized, multicentre assessment of the efficacy and safety of ASAQ – a fixed-dose artesunate-amodiaquine combination therapy in the treatment of uncomplicated Plasmodium falciparum malaria

    Directory of Open Access Journals (Sweden)

    Diallo Mouctar

    2009-06-01

    Full Text Available Abstract Background The use of artemisinin derivative-based combination therapy (ACT such as artesunate plus amodiaquine is currently recommended for the treatment of uncomplicated Plasmodium falciparum malaria. Fixed-dose combinations are more adapted to patients than regimens involving multiple tablets and improve treatment compliance. A fixed-dose combination of artesunate + amodiaquine (ASAQ was recently developed. To assess the efficacy and safety of this new combination and to define its optimum dosage regimen (once or twice daily in the treatment of uncomplicated P. falciparum malaria, a multicentre clinical study was conducted. Methods A multicentre, randomized, controlled, investigator-blinded, parallel-group study was conducted in five African centers in Cameroon, Madagascar, Mali and Senegal from March to December 2006. Efficacy and safety of ASAQ were assessed compared to those of artemether + lumefantrine (AL. The WHO protocol with a 28-day follow-up for assessing the drug therapeutic efficacy was used. Patients suffering from uncomplicated P. falciparum malaria were randomized to receive ASAQ orally once daily (ASAQ1, ASAQ twice daily (ASAQ2 or AL twice daily (AL for three days. The primary outcome was PCR-corrected parasitological cure rate and clinical response. Results Of 941 patients initially randomized and stratified into two age groups ( Conclusion The non-inferiority of ASAQ compared with AL was demonstrated. The fixed-dose combination artesunate + amodiaquine (ASAQ is safe and efficacious even in young children under 5 years of age. Whilst administration on a twice-a-day basis does not improve the efficacy of ASAQ significantly, a once-a-day intake of this new combination clearly appears as an effective and safe therapy in the treatment of uncomplicated P. falciparum malaria both in adults and children. Implications of such findings are of primary importance in terms of public health especially in African countries. As

  9. A Phase I-II dose escalation study of fixed-dose rate gemcitabine, oxaliplatin and capecitabine every two weeks in advanced cholangiocarcinomas

    DEFF Research Database (Denmark)

    Lassen, Ulrik; Jensen, Lars Henrik; Sorensen, Morten;

    2011-01-01

    ) and capecitabine (C), and evaluate the safety and efficacy of this regimen in patients with advanced cholangiocarcinoma (CC). METHODS: In the Phase I part of the study a dose-escalation schedule of FDR G, O and C, administered every two weeks, was performed in patients with solid tumours and no other treatments...

  10. Peak purity assessment in a triple-active fixed-dose combination drug product related substances method using a commercial two-dimensional liquid chromatography system.

    Science.gov (United States)

    Shackman, Jonathan G; Kleintop, Brent L

    2014-10-01

    Pharmaceutical formulations containing multiple active components challenge the development of analytical methods, especially as the individual active ingredients diverge in their physicochemical properties. Establishing specificity, especially peak purity, is one of the major evaluation criteria when developing a related substances method for drug substances or products. Fixed-dose combination products may not be amenable to common strategies for assessing peak purity, such as performing orthogonal separations, due to the complexity of the separation and/or diversity of the active ingredients. An alternate approach to evaluating peak purity is demonstrated for a triple-active component fixed-dose combination product under development. A commercially available automated two-dimensional liquid chromatography system was used to perform a selective comprehensive multidimensional separation of an active ingredient peak. The first dimension performed the drug product impurity/degradant profiling method; the second dimension assayed these fractions using the drug substance profiling method, which was pseudo-orthogonal to the first dimension. A total of 14 targeted fractions were sampled across the first dimension main peak, with 11 containing detectable analytes and the remaining fractions bracketing the main peak. This degree of sampling allowed profiling of a coeluting degradant present at a 0.2% w/w level throughout the main peak.

  11. Sitagliptin/metformin fixed-dose combination in type 2 diabetes mellitus: an evidence-based review of its place in therapy

    Directory of Open Access Journals (Sweden)

    Hayes J

    2016-07-01

    Full Text Available Jennifer Hayes,1 Rosie Anderson,1 Jeffrey W Stephens1,2 1Department of Diabetes and Endocrinology, Morriston Hospital, ABM University NHS Trust, 2Diabetes Research Group, Institute of Life Sciences, Swansea University, Swansea, UK Abstract: Type 2 diabetes mellitus is a progressive disease associated with significant morbidity and mortality. There is good evidence showing that intensive glycemic control reduces the development and progression of complications. In order to achieve glycemic targets, patients often require a combination of oral therapy and/or insulin in addition to lifestyle modification. Unfortunately, many of the traditional therapies for type 2 diabetes are associated with weight gain and hypoglycemia, resulting in poor compliance and subsequent worsening of glycemic control. The dipeptidyl peptidase-4 inhibitor sitagliptin is a therapy for type 2 diabetes and is available as a fixed-dose combination with metformin. Phase III clinical trials have demonstrated beneficial effects on glycemic control and minimal untoward effects with this combination. In this article, we provide an overview of the pharmacology, efficacy, and safety and examine the role of this combination within current practice. Keywords: sitagliptin, metformin, fixed-dose combination, type 2 diabetes

  12. Hematologic toxicity of gemcitabine: a comparison between fixed-dose rate infusion and thirty-minute infusion in the treatment of malignancy

    Institute of Scientific and Technical Information of China (English)

    Chunyan Li; Li Chu; Hui Han; Xi Liu; Yuping Shen; Mantang Qiu; Qing Xu

    2012-01-01

    Objective: The aim of the study was to compare the hematologic toxicity of gemcitabine between fixed-dose rate (FDR) infusion and 30-minute standard infusion in the treatment of malignancy. Methods: The 25 malignancy patients confirmed by histopathology or cytology received single-agent gemcitabine or gemcitabine in combination with other chemo-therapeutic agents. These patients were randomly divided into gemcitabine 1000 mg/m2 on d1, d8 at a rate of 10 mg/m2/min arm (FDR arm) or 30 min arm (standard arm), every 21 days one cycle. Hematologic toxicity was evaluated at the end of each cycle. Results: The 13 of 25 patients received gemcitabine FDR therapy, a total of 28 cycles was completed, and 32 cycles in the others (12 of 25 patients) with the standard arm. All patients were evaluable for hematologic toxicity. The result showed that the grades 3–4 leucopenia was significantly different between the two arms (14.3% vs 0, P 0.05, respectively) were observed between the two arms, no grade 4 of hemoglobin suppression was observed. Conclusion: Hematologic toxicity of gemcitabine therapy at a fixed-dose rate for malignancy is tolerable.

  13. Safety, tolerability, and efficacy of a fixed-dose combination of olmesartan 40 mg and hydrochlorothiazide 12.5/25 mg in daily practice

    Science.gov (United States)

    Bramlage, Peter; Zemmrich, Claudia; Ketelhut, Reinhard; Wolf, Wolf-Peter; Fronk, Eva-Maria; Schmieder, Roland E

    2013-01-01

    Background The safety and efficacy of olmesartan 40 mg and hydrochlorothiazide (HCTZ) as a fixed-dose combination has been investigated in clinical trials leading to its approval. The aims of the present study were to confirm these data in an unselected patient population in daily practice and to determine the impact of physical activity on blood pressure control. Methods In a multicenter, noninterventional study, 3,333 patients with either insufficient blood pressure control on olmesartan 40 mg alone or on a fixed/free combination of olmesartan 40 mg and HCTZ 12.5/25 mg were primarily assessed for safety and tolerability of the fixed-dose combination of olmesartan 40 mg and HCTZ 12.5/25 mg at 24 ± 2 weeks. Secondary objectives were blood pressure reduction, treatment compliance, and impact of physical activity as measured by the sum of weekly energy costs. Results The mean patient age was 63.2 ± 11.46 years, mean baseline blood pressure was 159.6 ± 15.28/93.5 ± 9.52 mmHg, and 70.9% had at least one additional cardiovascular risk factor. Adverse drug reactions were rare (n = 19), and no serious adverse drug reactions occurred. Compliance with drug therapy was at least sufficient in more than 99% of patients at the end of the study. Blood pressure at the last available visit was reduced by 26.1 ± 15.5/13.0 ± 10.1 mmHg versus baseline (P olmesartan 40 mg and HCTZ 12.5/25 mg in a large, unselected patient population, independent of physical activity level. PMID:24039432

  14. Efficacy and safety of fixed-dose artesunate-amodiaquine vs. artemether-lumefantrine for repeated treatment of uncomplicated malaria in Ugandan children.

    Directory of Open Access Journals (Sweden)

    Adoke Yeka

    Full Text Available The safety and efficacy of the two most widely used fixed-dose artemisinin-based combination therapies (ACT, artesunate-amodiaquine (ASAQ and artemether-lumefantrine (AL are well established for single episodes of uncomplicated Plasmodium falciparum malaria, but the effects of repeated, long-term use are not well documented. We conducted a 2-year randomized, open-label, longitudinal, phase IV clinical trial comparing the efficacy and safety of fixed-dose ASAQ and AL for repeated treatment of uncomplicated malaria in children under 5 years at Nagongera Health Centre, Uganda. Participants were randomized to ASAQ or AL and all subsequent malaria episodes were treated with the same regimen. 413 children were enrolled and experienced a total of 6027 malaria episodes (mean 15; range, 1-26. For the first malaria episode, the PCR-corrected-cure rate for ASAQ (97.5% was non-inferior to that for AL (97.0%; 95% CI [-0.028; 0.037]. PCR-corrected cure rates for subsequent malaria episodes that had over 100 cases (episodes 2-18, ranged from 88.1% to 98.9% per episode, with no clear difference between the treatment arms. Parasites were completely cleared by day 3 for all malaria episodes and gametocyte carriage was less than 1% by day 21. Fever clearance was faster in the ASAQ group for the first episode. Treatment compliance for subsequent episodes (only first dose administration observed was close to 100%. Adverse events though common were similar between treatment arms and mostly related to the disease. Serious adverse events were uncommon, comparable between treatment arms and resolved spontaneously. Anemia and neutropenia occurred in <0.5% of cases per episode, abnormal liver function tests occurred in 0.3% to 1.4% of cases. Both regimens were safe and effective for repeated treatment of malaria.Current Controlled Trials NCT00699920.

  15. Rationale for triple fixed-dose combination therapy with an angiotensin II receptor blocker, a calcium channel blocker, and a thiazide diuretic

    Directory of Open Access Journals (Sweden)

    Volpe M

    2012-06-01

    Full Text Available Massimo Volpe,1,2 Giuliano Tocci21Division of Cardiology, Department of Clinical and Molecular Medicine, University of Rome, Sapienza, Sant'Andrea Hospital, Rome, 2IRCCS Neuromed, Pozzilli, ItalyAbstract: Hypertension is a growing global health problem, and is predicted to affect 1.56 billion people by 2025. Treatment remains suboptimal, with control of blood pressure achieved in only 20%–35% of patients, and the majority requiring two or more antihypertensive drugs to achieve recommended blood pressure goals. To improve blood pressure control, the European hypertension guidelines recommend that angiotensin II receptor blockers (ARBs or angiotensin-converting enzyme inhibitors (ACEIs are combined with calcium channel blockers (CCBs and/or thiazide diuretics. The rationale for this strategy is based, in part, on their different effects on the renin-angiotensin system, which improves antihypertensive efficacy. Data from a large number of trials support the efficacy of ACEIs or ARBs in combination with CCBs and/or hydrochlorothiazide (HCTZ. Combining two different classes of antihypertensive drugs has an additive effect on lowering of blood pressure, and does not increase adverse events, with the ARBs showing a tolerability advantage over the ACEIs. Among the different ARBs, olmesartan medoxomil is available as a dual fixed-dose combination with either amlodipine or HCTZ, and the increased blood pressure-lowering efficacy of these two combinations is proven. Triple therapy is required in 15%–20% of treated uncontrolled hypertensive patients, with a renin-angiotensin system blocker, CCB, and thiazide diuretic considered to be a rational combination according to the European guidelines. Olmesartan, amlodipine, and HCTZ are available as a triple fixed-dose combination, and significant blood pressure reductions have been observed with this regimen compared with the possible dual combinations. The availability of these fixed-dose combinations should

  16. Effect of body weight on fixed dose of diclofenac for the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis

    DEFF Research Database (Denmark)

    Leerhøy, Bonna; Nordholm-Carstensen, Andreas; Novovic, Srdan

    2016-01-01

    OBJECTIVE: The aim of this study was to assess the influence of patient body weight on the clinical effect of 100 mg diclofenac administered as a single dose for the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP). MATERIALS AND METHODS: All patients subjected...... to endoscopic retrograde cholangiopancreatography (ERCP) from 2009 to 2014 were evaluated for inclusion. In total, 772 patients were included of whom 378 (49%) received diclofenac prophylaxis. RESULTS: In the diclofenac prophylaxis group, body weight was higher in patients with PEP (mean ± SD: 82 ± 18 kg) than...... of 100 mg diclofenac for the prophylaxis of PEP. CONCLUSIONS: High patient body weight was associated with a reduced effect of 100 mg diclofenac for prophylaxis of PEP....

  17. Prophylaxis of Postoperative Nausea and Vomiting in Adolescent Patients: A Review with Emphasis on Combination of Fixed-Dose Ondansetron and Transdermal Scopolamine

    Directory of Open Access Journals (Sweden)

    Joseph V. Pergolizzi

    2011-01-01

    Full Text Available Postoperative nausea and vomiting (PONV is a relatively common occurrence (20–30% that delays discharge and, if persistent, can lead to serious complications. The incidence of PONV is a function of patient characteristics, the type and duration of surgery, the type of anesthesia, and the choice of pre-, intra-, and postoperative pharmacotherapy. There are no completely effective antiemetic agents for this condition, but recommendations for treatment strategies are separately available for pediatric and adult patients. Left unclear is whether adolescents should be guided by the pediatric or the adult recommendations. We review the developmental physiology of the relevant physiological factors (absorption, distribution, metabolism, and elimination. We also review the clinical evidence regarding the safety and efficacy of a fixed-dose combination of ondansetron (4 mg, i.v. and transdermal scopolamine (1.5 mg.

  18. 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

  19. Pooled safety analysis of the fixed-dose combination of indacaterol and glycopyrronium (QVA149), its monocomponents, and tiotropium versus placebo in COPD patients

    DEFF Research Database (Denmark)

    Wedzicha, Jadwiga A; Dahl, Ronald; Buhl, Roland

    2014-01-01

    BACKGROUND: To further assess the safety profile of the fixed-dose combination of indacaterol and glycopyrronium (QVA149) and its monocomponents; we investigated the impact of individual patient-level factors and time by integrating the patient-level safety data from the QVA149 clinical programme...... with relevant information from the independent indacaterol and glycopyrronium safety databases. METHODS: Data from 11,404 patients with chronic obstructive pulmonary disease (COPD) were pooled from 14 clinical studies of QVA149, indacaterol and glycopyrronium of ≥3 month's duration with at least two...... of the treatment groups: QVA149 110/50 μg, glycopyrronium 50 μg, indacaterol 150 μg, placebo or tiotropium 18 μg. Overall hazard ratio (HR) was assessed between the active treatments and placebo and in various subgroups related to severity of airways obstruction, inhaled corticosteroid use, cardiovascular risk...

  20. Pooled safety analysis of the fixed-dose combination of indacaterol and glycopyrronium (QVA149), its monocomponents, and tiotropium versus placebo in COPD patients.

    Science.gov (United States)

    Wedzicha, Jadwiga A; Dahl, Ronald; Buhl, Roland; Schubert-Tennigkeit, Agnes; Chen, Hungta; D'Andrea, Peter; Fogel, Robert; Banerji, Donald

    2014-10-01

    To further assess the safety profile of the fixed-dose combination of indacaterol and glycopyrronium (QVA149) and its monocomponents; we investigated the impact of individual patient-level factors and time by integrating the patient-level safety data from the QVA149 clinical programme with relevant information from the independent indacaterol and glycopyrronium safety databases. Data from 11,404 patients with chronic obstructive pulmonary disease (COPD) were pooled from 14 clinical studies of QVA149, indacaterol and glycopyrronium of ≥3 month's duration with at least two of the treatment groups: QVA149 110/50 μg, glycopyrronium 50 μg, indacaterol 150 μg, placebo or tiotropium 18 μg. Overall hazard ratio (HR) was assessed between the active treatments and placebo and in various subgroups related to severity of airways obstruction, inhaled corticosteroid use, cardiovascular risk factors, sex, age and body mass index for death, serious cases of cardio- and cerebrovascular (CCV) events, major adverse cardiovascular events (MACEs), pneumonia, COPD exacerbations requiring hospitalisation or atrial flutter/fibrillation (AF/F). The HR for QVA149 versus placebo showed no significant increase in the overall risk for death (HR [95% confidence interval]: 0.93 [0.34-2.54]); CCV events (0.60 [0.29-1.24]); MACE (1.04 [0.45-2.42]); pneumonia (1.10 [0.54-2.25]); COPD exacerbations (0.60 [0.40-0.91]); and AF/F (1.03 [0.49-2.18]). Similar results were observed for indacaterol, glycopyrronium and tiotropium versus placebo for overall risk and in analysed subgroups. There was no increase in the risk for the investigated safety endpoints for the fixed-dose combination QVA149, and it had a comparable safety profile as its monocomponents and tiotropium versus placebo. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. A replicate designed bioequivalence study to compare two fixed-dose combination products of artesunate and amodiaquine in healthy chinese volunteers.

    Science.gov (United States)

    Liu, Yun; Hu, Chaoying; Liu, Gangyi; Jia, Jingying; Yu, Chen; Zhu, Jianmin; Zheng, Qingsi; Zhang, Kanyin E

    2014-10-01

    Artesun-Plus is a fixed-dose combination antimalarial agent containing artesunate and amodiaquine. The current study was conducted to compare the pharmacokinetic and safety profiles of Artesun-Plus and the WHO-designated comparator product Artesunate Amodiaquine Winthrop. To overcome the high intrasubject variability of artesunate, the study applied a two-sequence and four-period crossover (2 by 4), replicate study design to assess bioequivalence between the two products in 31 healthy male Chinese volunteers under fasting conditions. The results showed that the values of the geometric mean ratios of maximum concentration of drug in plasma (Cmax) and area under the concentration-time curve from time zero to the last blood sample collection (AUC0-last) for the artesunate component in the test and reference products were 95.9% and 93.9%, respectively, and that the corresponding 90% confidence intervals were 84.5% to 108.7% and 87.2% to 101.1%, while the geometric mean ratios for the amodiaquine component in the test and reference products were 95.0% and 100.0%, respectively, and the corresponding 90% confidence intervals were 86.7% to 104.1% and 93.5% to 107.0%. In conclusion, bioequivalence between the two artesunate and amodiaquine fixed-dose combination products was demonstrated for both components. The study also confirmed high intrasubject variability, especially for artesunate: the coefficients of variation (CV) of Cmax values for the test and reference products were 39.2% and 43.7%, respectively, while those for amodiaquine were 30.6% and 30.2%, respectively.

  2. Pharmacokinetic non-interaction analysis in a fixed-dose formulation in combination of atorvastatin and ezetimibe

    Directory of Open Access Journals (Sweden)

    Omar ePatiño-Rodríguez

    2014-11-01

    Full Text Available Recent clinical research has shown that atorvastatin in combination with cholesterol absorption inhibitor ezetimibe significantly reduces LDL-C level in patients with hypercholesterolemia, showing a superior lipid-lowering efficacy compared to statin alone. With no information currently available on the interaction between the two drugs, a pharmacokinetic study was conducted to investigate the influence of ezetimibe on atorvastatin and conversely when the two drugs were coadministered. The purpose of this study was to investigate the presence of differences in the pharmacokinetic profiles of capsules containing atorvastatin 80 mg, ezetimibe 10 mg or the combination of both 80/10 mg administered to healthy Mexican volunteers. This was a randomized, three-period, six-sequences crossover study. 36 eligible subjects aged between 20 to 50 years were included. Blood samples were collected up to 96 h after dosing, and pharmacokinetic parameters were obtained by non-compartmental analysis. Adverse events were evaluated based on subject interviews and physical examinations. Area under the concentration-time curve (AUC and maximum plasma drug concentration (Cmax were measured for each drug alone or together and tested for bioequivalence-based hypothesis. The estimation computed (90% confidence intervals for AUC and Cmax, were 96.04% (85.88%–107.42% and 97.04% (82.36%–114.35%, respectively for atorvastatin-ezetimibe combination versus atorvastatin alone, while 84.42% (77.19%–92.32% and 95.60% (82.43%–110.88%, respectively, for atorvastatin-ezetimibe combination versus ezetimibe alone were estimated. These results suggest that atorvastatin and ezetimibe have no relevant pharmacokinetic drug-drug interaction.

  3. 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

    Energy Technology Data Exchange (ETDEWEB)

    Ben-Josef, Edgar, E-mail: edgar.ben-josef@uphs.upenn.edu [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Schipper, Mathew [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Francis, Isaac R. [Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Hadley, Scott; Ten-Haken, Randall; Lawrence, Theodore; Normolle, Daniel [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Simeone, Diane M.; Sonnenday, Christopher [Department of Surgery, University of Michigan, Ann Arbor, Michigan (United States); Abrams, Ross [Department of Radiation Oncology, Rush Medical Center, Chicago, Illinois (United States); Leslie, William [Division of Hematology Oncology, Department of Internal Medicine, Rush Medical Center, Chicago, Illinois (United States); Khan, Gazala; Zalupski, Mark M. [Division of Hematology Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan (United States)

    2012-12-01

    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{sup 3}, platelets {>=}100,000/mm{sup 3}, creatinine <2 mg/dL, bilirubin <3 mg/dL, and alanine aminotransferase/aspartate aminotransferase {<=}2.5 Multiplication-Sign upper limit of normal. FDR-G (1000 mg/m{sup 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

  4. Safety, tolerability, and efficacy of a fixed-dose combination of olmesartan 40 mg and hydrochlorothiazide 12.5/25 mg in daily practice

    Directory of Open Access Journals (Sweden)

    Bramlage P

    2013-08-01

    Full Text Available Peter Bramlage,1 Claudia Zemmrich,1 Reinhard Ketelhut,2 Wolf-Peter Wolf,3 Eva-Maria Fronk,4 Roland E Schmieder5 1Institut für Pharmakologie und Präventive Medizin, Mahlow, Germany; 2Institut für Sportmedizin, Universitätsklinikum Charité, Humboldt Universität zu Berlin, Berlin, Germany; 3Daiichi Sankyo Deutschland GmbH, Munich, Germany; 4Daiichi Sankyo Europe GmbH, Munich, Germany; 5Universitätsklinikum Erlangen, Klinik für Nephrologie und Hypertensiologie, Erlangen, Germany Background: The safety and efficacy of olmesartan 40 mg and hydrochlorothiazide (HCTZ as a fixed-dose combination has been investigated in clinical trials leading to its approval. The aims of the present study were to confirm these data in an unselected patient population in daily practice and to determine the impact of physical activity on blood pressure control. Methods: In a multicenter, noninterventional study, 3,333 patients with either insufficient blood pressure control on olmesartan 40 mg alone or on a fixed/free combination of olmesartan 40 mg and HCTZ 12.5/25 mg were primarily assessed for safety and tolerability of the fixed-dose combination of olmesartan 40 mg and HCTZ 12.5/25 mg at 24 ± 2 weeks. Secondary objectives were blood pressure reduction, treatment compliance, and impact of physical activity as measured by the sum of weekly energy costs. Results: The mean patient age was 63.2 ± 11.46 years, mean baseline blood pressure was 159.6 ± 15.28/93.5 ± 9.52 mmHg, and 70.9% had at least one additional cardiovascular risk factor. Adverse drug reactions were rare (n = 19, and no serious adverse drug reactions occurred. Compliance with drug therapy was at least sufficient in more than 99% of patients at the end of the study. Blood pressure at the last available visit was reduced by 26.1 ± 15.5/13.0 ± 10.1 mmHg versus baseline (P < 0.0001, but had reduced effectiveness in patients ≥75 years with diabetes or impaired renal function. In 69% of patients

  5. S-Adenosyl-L-Methionine Augmentation in Patients with Stage II Treatment-Resistant Major Depressive Disorder: An Open Label, Fixed Dose, Single-Blind Study

    Directory of Open Access Journals (Sweden)

    Domenico De Berardis

    2013-01-01

    Full Text Available We investigated the efficacy of S-Adenosyl-L-Methionine (SAMe augmentation in patients with treatment-resistant depressive disorder (TRD. Thirty-three outpatients with major depressive episode who failed to respond to at least 8 weeks of treatment with two adequate and stable doses of antidepressants were treated openly with fixed dose of SAMe (800 mg for 8 weeks, added to existing medication. The primary outcome measure was the change from baseline in total score on Hamilton Rating Scale for Depression (HAM-D. The Clinical Global Impression of Improvement (CGI-I was rated at the endpoint. Patients with a reduction of 50% or more on HAM-D total score and a CGI-I score of 1 or 2 at endpoint were considered responders; remission was defined as a HAM-D score ≤7. Secondary outcome measures included the Snaith-Hamilton Pleasure Scale (SHAPS and the Sheehan Disability Scale (SDS. At 8 weeks, a significant decrease in HAM-D score was observed with response achieved by 60% of the patients and remission by 36%. Also a statistically significant reduction in SHAPS and SDS was observed. Our findings indicate that SAMe augmentation may be effective and well tolerated in stage II TRD. However, limitations of the present study must be considered and further placebo-controlled trials are needed.

  6. UK-specific cost-effectiveness of tiotropium + olodaterol fixed-dose combination versus other LAMA + LABA combinations in patients with COPD.

    Science.gov (United States)

    Tebboth, Abigail; Ternouth, Andrew; Gonzalez-Rojas, Nuria

    2016-01-01

    The aim of this study is to assess the cost-effectiveness of other long-acting muscarinic antagonist + long-acting β2 agonist combinations in comparison with Spiolto(®) Respimat(®) (tiotropium + olodaterol fixed-dose combination [FDC]) for maintenance treatment to relieve symptoms in adult patients with chronic obstructive pulmonary disease. A previously published individual-level Markov model was adapted for the perspective of the UK health care system, in line with recommendations from the National Institute for Health and Care Excellence. Individuals progressed through the model based on their forced expiratory volume in 1 second (FEV1) value at baseline and the post-improvement FEV1 value. Changes in FEV1 were taken from a mixed treatment comparison. Costs were obtained from a published cost-utility analysis of tiotropium in the treatment of chronic obstructive pulmonary disease in the UK. Uncertainty was assessed by deterministic and probabilistic sensitivity analysis. Duaklir(®) Genuair(®) (aclidinium bromide + formoterol fumarate FDC) and the free-dose combination of tiotropium + salmeterol were dominated by tiotropium + olodaterol FDC. The quality-adjusted life years and costs were identical for Ultibro(®) Breezhaler(®) (indacaterol + glycopyrronium FDC) and Anoro(™) Ellipta(®) (umeclidinium + vilanterol FDC) compared with tiotropium + olodaterol FDC, resulting in identical incremental cost-effectiveness ratios. This analysis shows tiotropium + olodaterol FDC to be a cost-effective option for the maintenance treatment of adults with chronic obstructive pulmonary disease in the UK.

  7. Hot-melt co-extrusion for the production of fixed-dose combination products with a controlled release ethylcellulose matrix core.

    Science.gov (United States)

    Vynckier, A-K; Dierickx, L; Saerens, L; Voorspoels, J; Gonnissen, Y; De Beer, T; Vervaet, C; Remon, J P

    2014-04-10

    In this study, hot-melt co-extrusion was evaluated as a technique for the production of fixed-dose combination products, using ethylcellulose as a core matrix former to control the release of metoprolol tartrate and a polyethylene oxide-based coat formulation to obtain immediate release of hydrochlorothiazide. By lowering the concentration of the hydrophilic additive polyethylene oxide in the plasticized ethylcellulose matrix or by lowering the drug load, the in vitro metoprolol tartrate release from the core was substantially sustained. The in vitro release of hydrochlorothiazide from the polyethylene oxide/polyethylene glycol coat was completed within 45 min for all formulations. Tensile testing of the core/coat mini-matrices revealed an adequate adhesion between the two layers. Raman mapping showed no migration of active substances. Solid state characterization indicated that the crystalline state of metoprolol tartrate was not affected by thermal processing via hot-melt extrusion, while hydrochlorothiazide was amorphous in the coat. These solid state characteristics were confirmed during the stability study. Considering the bioavailability of metoprolol tartrate after oral administration to dogs, the different co-extruded formulations offered a range of sustained release characteristics. Moreover, high metoprolol tartrate plasma concentrations were reached in dogs allowing the administered dose to be halved.

  8. Evaluation of gonadotropin-releasing hormone hydrogen chloride at 3 doses with prostaglandin F2α for fixed-time artificial insemination in dairy cows.

    Science.gov (United States)

    Chenault, J R; Meeuwse, D M; LaGrow, C; Tena, J-K S; Wood-Follis, S L; Hallberg, J W

    2014-05-01

    The objectives of the current study were to evaluate the efficacy and field safety of GnRH HCl administered at 3 doses in fixed-time artificial insemination (FTAI) programs (Ovsynch) in dairy cows. A common protocol was conducted at 6 commercial dairies. Between 188 and 195 cows were enrolled at each site (total enrolled = 1,142). Cows had body condition scores ≥ 2 and ≤ 4, were between 32 to 140 d in milk, and were clinically healthy. Within pen and enrollment day (enrollment cohort), cows were assigned randomly in blocks of 4 to each of 4 treatments: (1) 25mg of PGF2α on d 7 with FTAI 72 ± 2 h later (control); (2) 100 μg of GnRH on d 0, d 7 a dose of 25mg of PGF2α, and the second administration of 100 μg of GnRH (T100) administered either at 48 ± 2 h (d 9) after PGF2α with FTAI 24 ± 2 h later or 56 ± 2 h (d 9) after PGF2α and FTAI 17 ± 2 h later; (3) same as T100 with both injections of 150 μg of GnRH (T150); and (4) same as T100 with both injections of 200 μg of GnRH (T200). Three sites selected the first option and 3 sites selected the second option for the timing of the second injection of all doses of GnRH. Cows were observed daily for signs of estrus and adverse clinical signs. Cows not returning to estrus had pregnancy diagnosis between 42 and 65 d following FTAI. Pregnancies per FTAI (P/FTAI) were analyzed as a binary variable (1 = pregnant, 0 = not pregnant) using a generalized linear mixed model with a binomial error distribution and a logit link function. The statistical model included fixed effects for treatment, random effects of site, site by treatment, enrollment cohort within site, and residual. Parity (first vs. second or greater) was included as a covariate. For demonstration of effectiveness, α=0.05 and a 2-tailed test were used. Fifty-two cows were removed from the study because of either deviation from the protocol, injury, illness, culling, or death. Among the remaining 1,090 cows, 33.9% were primiparous and 66.1% were

  9. Dosimetric and efficiency comparison of high-dose radiotherapy for esophageal cancer: volumetric modulated arc therapy versus fixed-field intensity-modulated radiotherapy.

    Science.gov (United States)

    Lin, C-Y; Huang, W-Y; Jen, Y-M; Chen, C-M; Su, Y-F; Chao, H-L; Lin, C-S

    2014-08-01

    The aim of this study was to compare high-dose volumetric modulated arc therapy (VMAT) and fixed-field intensity-modulated radiotherapy (ff-IMRT) plans for the treatment of patients with middle-thoracic esophageal cancer. Eight patients with cT2-3N0M0 middle-thoracic esophageal cancer were enrolled. The treatment planning system was the version 9 of the Pinnacle(3) with SmartArc (Philips Healthcare, Fitchburg, WI, USA). VMAT and ff-IMRT treatment plans were generated for each case, and both techniques were used to deliver 50 Gy to the planning target volume (PTV(50)) and then provided a 16-Gy boost (PTV(66)). The VMAT plans provided superior PTV(66) coverage compared with the ff-IMRT plans (P = 0.034), whereas the ff-IMRT plans provided more appropriate dose homogeneity to the PTV(50) (P = 0.017). In the lung, the V(5) and V(10) were lower for the ff-IMRT plans than for the VMAT plans, whereas the V(20) was lower for the VMAT plans. The delivery time was significantly shorter for the VMAT plans than for the ff-IMRT plans (P = 0.012). In addition, the VMAT plans delivered fewer monitor units. The VMAT technique required a shorter planning time than the ff-IMRT technique (3.8 ± 0.8 hours vs. 5.4 ± 0.6 hours, P = 0.011). The major advantages of VMAT plans are higher efficiency and an approximately 50% reduction in delivery time compared with the ff-IMRT plans, with comparable plan quality. Further clinical investigations to evaluate the use of high-dose VMAT for the treatment of esophageal cancer are warranted. © 2013 Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

  10. Bioequivalence Study of a New Fixed-dose Combination Tablet Containing S-Amlodipine Nicotinate and Olmesartan Medoxomil in Healthy Korean Male Subjects.

    Science.gov (United States)

    Oh, Mi Jin; Hwang, Hyun Hwan; Kim, Hyun Gyu; Lee, Geun Hyeog; Cho, Yun-Seok; Lee, Sun Young; Kang, Soo Yeon; Cho, Kyung Hee; Lee, Yun Young; Lee, Yun Jeong; Jang, Choon-Gon; Lee, Seok-Yong

    2017-07-01

    A fixed-dose combination (FDC) pill of amlodipine (relatively old calcium channel blocker as dihydropyridine) and olmesartan (relatively new angiotensin II receptor blocker) is used for hypertension that is not adequately controlled with a single-formulation drug. Because the FDC is a one-pill formulation, and amlodipine and olmesartan have different mechanisms of action, it is expected to improve patients' medication compliance and have an increased blood pressure-lowering efficacy. The purpose of this study was to assess the safety profile and the bioequivalence of two different FDC formulations [amlodipine besylate/olmesartan medoxomil 10/40 mg (reference product) and S-amlodipine nicotinate/olmesartan medoxomil 5/40 mg (test product)]. A randomized, open-label, single-dose, 2-treatment, 2-way, and 2-period crossover study, including a 3-week washout period, was performed in 32 healthy Korean male volunteers. To analyze the concentration of S-amlodipine or olmesartan, plasma samples were collected up to 144 hours after the dose for S-amlodipine and 48 hours after the dose for olmesartan. Pharmacokinetic parameters, including the Cmax and the area under the curve from time 0 to the last measurable concentration (AUC0-last) for the time versus concentration plot, were calculated. Analysis of variance for bioequivalence was conducted using Cmax and AUC0-last converted to log scale, and the mean ratios and 90% CIs were determined. Safety data included analysis of adverse events (AEs), vital signs, physical examinations, clinical laboratory test, and 12-lead ECGs. Of the 32 enrolled participants, 29 healthy volunteers completed the study. For both S-amlodipine and olmesartan, the main pharmacokinetic parameters were all within the acceptable range for regulatory bioequivalence. The 90% CIs for the geometric mean ratios of Cmax and AUC0-last were 0.8766 to 0.9760 and 0.8288 to 0.9224, respectively, for S-amlodipine and 0.9097 to 1.1229 and 0.8904 to 1

  11. Evaluating the role of atazanavir/cobicistat and darunavir/cobicistat fixed-dose combinations for the treatment of HIV-1 infection

    Directory of Open Access Journals (Sweden)

    Crutchley RD

    2016-03-01

    Full Text Available Rustin D Crutchley,1 Rakesh C Guduru,2 Amy M Cheng1 1Department of Pharmacy Practice and Translational Research, College of Pharmacy, University of Houston, 2CompanionDX, Houston, TX, USA Abstract: Atazanavir/cobicistat (ATV/c and darunavir/cobicistat (DRV/c are newly approved once daily fixed-dose protease inhibitor combinations for the treatment of HIV-1 infection. Studies in healthy volunteers have established bioequivalence between cobicistat and ritonavir as pharmacoenhancers of both atazanavir (ATV and darunavir (DRV. In addition, two randomized clinical trials (one Phase II and one Phase III noninferiority trial with a 144-week follow-up period demonstrated that cobicistat had sustainable and comparable efficacy and safety to ritonavir as a pharmacoenhancer of ATV through 144 weeks of treatment in HIV-1-infected patients. Furthermore, one Phase III, open-label, single-arm, clinical trial reflected virologic and immunologic responses and safety outcomes consistent with prior published data for DRV/ritonavir 800/100 mg once daily, supporting the use of DRV/c 800/150 mg once daily for future treatment of treatment-naïve and -experienced HIV-1-infected patients with no DRV resistance-associated mutations. Low rates of virologic failure secondary to resistance to antiretroviral regimens were present in these clinical studies. Most notable adverse events in the ATV studies were hyperbilirubinemia and in the DRV study rash. Small increases in serum creatinine and minimally reduced estimated glomerular filtration rate Cockcroft–Gault calculation (eGFRCG were observed in ATV/c and DRV/c clinical studies consistent with other studies evaluating elvitegravir/cobicistat/tenofovir/emtricitabine for the treatment of HIV-1 infection. These renal parameter changes occurred acutely in the first few weeks and plateaued off for the remaining study periods and are not necessarily clinically relevant. Cobicistat has numerous advantages compared to

  12. Comparative evaluation of efficacy and safety of artesunate-lumefantrine vs. artemether-lumefantrine fixed-dose combination in the treatment of uncomplicated Plasmodium falciparum malaria.

    Science.gov (United States)

    Pareek, Anil; Chandurkar, Nitin; Srivastav, Vipul; Lakhani, Jitendra; Karmakar, Partha S; Basu, Subrata; Ray, Arnab; Pednekar, Sangeeta; Gupta, P B; Suthar, Nilay; Lakhani, Sucheta

    2013-05-01

    To establish efficacy and safety of artesunate/lumefantrine fixed-dose combination (FDC) in comparison with artemether/lumefantrine FDC in treatment of uncomplicated Plasmodium falciparum malaria. Confirmed cases of uncomplicated P. falciparum malaria were randomly assigned to receive artesunate (100 mg)/lumefantrine (480 mg) (ASLF FDC) or artemether (80 mg)/lumefantrine (480 mg) (AMLF FDC) tablets for 3 days. Patients were followed up on Day 7, 14, 21 and 28. Of the 158 enrolled patients, 144 completed the study. Seventy-three patients (94.8%) from the ASLF group and 71 patients (94.7%) from the AMLF group showed parasite clearance within 48 h. The mean parasite clearance time was 25.40 ± 14.82 h in the ASLF group and 24 ± 13.32 h in the AMLF group (P = 0.542). All patients showed gametocyte clearance by Day 7 and remained gametocyte free till Day 28. Sixty-five patients (84.4%) from the ASLF group and 56 patients (74.7%) from the AMLF group were afebrile within 24 h. The mean fever clearance time was 17.38 ± 12.33 h in the ASLF group and 17.2 ± 12.01 h in the AMLF group (P = 0.929). There was one early treatment failure in the AMLF group as per WHO criteria. Improvement in haemoglobin and haematocrit was comparable in both the treatment groups. In the ASLF group, of the 25 (32.47%) patients anaemic at baseline, only seven (9.09%) reported anaemia on Day 28, while in the AMLF group, of the 14 (18.67%) patients anaemic at baseline, only four (5.33%) reported anaemia on Day 28. Both study medications were well tolerated. Artesunate (100 mg)/lumefantrine (480 mg) fixed-dose combination could add one more option to currently available artemisinin combinations in treatment of uncomplicated P. falciparum malaria. © 2013 Blackwell Publishing Ltd.

  13. Efficacy of indacaterol 75 μg versus fixed-dose combinations of formoterol-budesonide or salmeterol-fluticasone for COPD: a network meta-analysis.

    Science.gov (United States)

    Cope, Shannon; Kraemer, Matthias; Zhang, Jie; Capkun-Niggli, Gorana; Jansen, Jeroen P

    2012-01-01

    The purpose of this study was to update our network meta-analysis in order to compare the efficacy of indacaterol 75 μg with that of a fixed-dose combination of formoterol and budesonide (FOR/BUD) and a fixed-dose combination salmeterol and fluticasone (SAL/FP) for the treatment of chronic obstructive pulmonary disease (COPD) based on evidence identified previously in addition to two new randomized clinical trials. Fifteen randomized, placebo-controlled clinical trials including COPD patients were evaluated: indacaterol 75 μg once daily (n = 2 studies), indacaterol 150 μg once daily (n = 5), indacaterol 300 μg once daily (n = 4), FOR/BUD 9/160 μg twice daily (n = 2), FOR/BUD 9/320 μg twice daily (n = 2), SAL/FP 50/500 μg twice daily (n = 4), and SAL/FP 50/250 μg twice daily (n = 1). All trials were analyzed simultaneously using a Bayesian network meta-analysis and relative treatment effects between all regimens were obtained. Treatment-by-covariate interactions were included where possible to improve the similarity of the trials. Outcomes of interest were trough forced expiratory volume in 1 second (FEV(1)) and transitional dyspnea index at 12 weeks. Based on the results without adjustment for covariates, indacaterol 75 μg resulted in a greater improvement in FEV(1) at 12 weeks compared with FOR/BUD 9/160 μg (difference in change from baseline 0.09 L [95% credible interval 0.04-0.13]) and FOR/BUD 9/320 μg (0.07 L [0.03-0.11]) and was comparable with SAL/FP 50/250 μg (0.00 L [-0.07-0.07]) and SAL/FP 50/500 μg (0.01 L [-0.04-0.05]). For transitional dyspnea index, data was available only for indacaterol 75 μg versus SAL/FP 50/500 μg (-0.49 points [-1.87-0.89]). Based on results of a network meta-analysis with and without covariates, indacaterol 75 μg is expected to be at least as efficacious as FOR/BUD (9/320 μg and 9/160 μg) and comparable with SAL/FP (50/250 μg and 50/500 μg) in terms of lung function. In terms of breathlessness (transitional

  14. An open randomized controlled trial to compare the efficacy of two fixed dose combinations of artemesinin based combinations for uncomplicated falciparum malaria in Bangladesh.

    Science.gov (United States)

    Samad, R; Rahman, M R; Yunus, E B; Hussain, M A; Arif, S M; Islam, M N; Hafiz, S A M M A; Hossain, M M; Faiz, M A

    2013-12-01

    National Malaria Control Program (NMCP) of Bangladesh has introduced Artemisinin Based Combination (ACT), Coartem(R) (Artemether-Lumefantrine (AL), fixed dose combination, in the confirmed cases of uncomplicated P. falciparum malaria since 2004. Despite the reduction of mortality due to malaria, the development and spread of anti-malarial drug resistance wordwide posing a threat to the health services and will make it difficult to control malaria in Bangladesh in future. We need to have an alternative to Coartem which could be Artesunate-amodiaquine (AA) in a fixed dose combination (FDC), a cheaper altenative not yet evidenced to be effective and safe to our population. In this study we compared the efficacy and safety of Artemether + Lumefantrene (FDC, Coartem) with Artesunate +Amodiaquine tablets (100/270 mg FDC) for the treatment of uncomplicated P. falciparum malaria in three high risk multi-drug resistant malaria prevalent areas of Bangladesh. It was an open label randomized controlled trial conducted between December 2008 and November 2009 in 4 upazillas in patients over the age 12 to 60 years diagnosed as a case of uncomplicated P. falciparum malaria. The outcome of the cases were measured as clinical response, parasitological response, defervescence time and parasite clearance time. Drug safety was assessed by comparing the adverse events. A total of 252 cases were randomized to receive Artesunate + Amodiaquine (AA group, 147 cases) and Artemether + Lumefantrene (AL group, 106 cases), one lost to follow up at day 28 in AA group. The distribution of the cases was comparable by age, sex and study sites. Treatment success' response was observed 100% in the AL group and AA group had 99%, two failures with AA were late treatment failures and the difference was not statistically significant (p > .1). The parasitological sensitive (S) response was observed in 97% of cases in AL group and 95% in the AA group, and was not a statistically significant difference

  15. A Real-World, Multicenter Assessment of Drugs Requiring Weight-Based Calculations in Overweight, Adult Critically Ill Patients

    Directory of Open Access Journals (Sweden)

    Sandra L. Kane-Gill

    2013-01-01

    Full Text Available Prescribing appropriate doses of drugs requiring weight-based dosing is challenging in overweight patients due to a lack of data. With 68% of the US population considered overweight and these patients being at an increased risk for hospitalization, clinicians need guidance on dosing weight-based drugs. The purpose of this study was to identify “real-world” dose ranges of high-risk medications administered via continuous infusion requiring weight-based dosing and determine the reasons for dosing changes (ineffectiveness or adverse drug reactions. A prospective, multicenter, observational study was conducted in four intensive care units at three institutions. A total of 857 medication orders representing 11 different high-risk medications in 173 patients were reviewed. It was noted that dosing did not increase in proportion to weight classification. Overall, 14 adverse drug reactions occurred in nine patients with more in overweight patients (9 of 14. A total of 75% of orders were discontinued due to ineffectiveness in groups with higher body mass indexes. Ineffectiveness leads to dosing adjustments resulting in the opportunity for medication errors. Also, the frequent dosing changes further demonstrate our lack of knowledge of appropriate dosing for this population. Given the medications’ increased propensity to cause harm, institutions should aggressively monitor these medications in overweight patients.

  16. Effect of food on the pharmacokinetics of canagliflozin/metformin (150/1,000 mg) immediate-release fixed-dose combination tablet in healthy participants.

    Science.gov (United States)

    Murphy, Joseph; Wang, Shean-Sheng; Stieltjes, Hans; Wajs, Ewa; Devineni, Damayanthi

    2015-03-01

    To assess the effect of food on the pharmacokinetics (PK) of canagliflozin and metformin following administration of a canagliflozin/metformin (150/1,000 mg) immediate-release (IR) fixed-dose combination (FDC) tablet. A randomized, open-label, singlecenter, single-dose, 2-period, 2-sequence crossover study was conducted in healthy participants. Participants were randomized to 2 sequences of fasted and fed (or vice versa) administration of one 150/1,000 mg canagliflozin/metformin IR FDC, with 10-14 day washout between treatments PK parameters (AUC, Cmax, tmax, t1/2) were assessed for canagliflozin and metformin. Safety was evaluated. When comparing the IR FDC tablet administered with and without food, PK parameters of canagliflozin were bioequivalent as the 90% confidence intervals (CIs) for log-transformed AUClast, AUC∞, and Cmax were within the bioequivalence limits of 80-125%. For metformin, overall exposure was similar under fed and fasted conditions as geometric mean ratios for AUC and associated 90% CI were contained within the bioequivalence limits, but geometric mean Cmax decreased by 16% in the fed compared to fasted state. Both treatments were well tolerated with similar adverse events and most common were gastrointestinal events, generally attributed to metformin. Food did not affect canagliflozin bioavailability parameters (Cmax and AUCs) or AUCs of metformin. The Cmax of metformin was decreased by 16%, which is not considered clinically meaningful. The canagliflozin/metformin FDC tablet is recommended to be taken with meals to reduce the symptoms of gastrointestinal intolerability associated with metformin.

  17. UK-specific cost-effectiveness of tiotropium + olodaterol fixed-dose combination versus other LAMA + LABA combinations in patients with COPD

    Directory of Open Access Journals (Sweden)

    Tebboth A

    2016-11-01

    Full Text Available Abigail Tebboth,1 Andrew Ternouth,1 Nuria Gonzalez-Rojas2 1Boehringer Ingelheim Ltd., Bracknell, UK; 2Boehringer Ingelheim GmBH, Ingelheim, Germany Objective: The aim of this study is to assess the cost-effectiveness of other long-acting muscarinic antagonist + long-acting β2 agonist combinations in comparison with Spiolto® Respimat® (tiotropium + olodaterol fixed-dose combination [FDC] for maintenance treatment to relieve symptoms in adult patients with chronic obstructive pulmonary disease.Methods: A previously published individual-level Markov model was adapted for the perspective of the UK health care system, in line with recommendations from the National Institute for Health and Care Excellence. Individuals progressed through the model based on their forced expiratory volume in 1 second (FEV1 value at baseline and the post-improvement FEV1 value. Changes in FEV1 were taken from a mixed treatment comparison. Costs were obtained from a published cost-utility analysis of tiotropium in the treatment of chronic obstructive pulmonary disease in the UK. Uncertainty was assessed by deterministic and probabilistic sensitivity analysis.Results: Duaklir® Genuair® (aclidinium bromide + formoterol fumarate FDC and the free-dose combination of tiotropium + salmeterol were dominated by tiotropium + olodaterol FDC. The quality-adjusted life years and costs were identical for Ultibro® Breezhaler® (indacaterol + glycopyrronium FDC and Anoro™ Ellipta® (umeclidinium + vilanterol FDC compared with tiotropium + olodaterol FDC, resulting in identical incremental cost-effectiveness ratios.Conclusion: This analysis shows tiotropium + olodaterol FDC to be a cost-effective option for the maintenance treatment of adults with chronic obstructive pulmonary disease in the UK. Keywords: COPD, economic, cost-effectiveness, tiotropium + olodaterol

  18. Pharmacokinetics and relative bioavailability of fixed-dose combination of clopidogrel and aspirin versus coadministration of individual formulations in healthy Korean men

    Science.gov (United States)

    Choi, Hyang-Ki; Ghim, Jong-Lyul; Shon, Jihong; Choi, Young-Kyung; Jung, Jin Ah

    2016-01-01

    Background Simultaneous prescription of clopidogrel and low-dose aspirin is recommended for the treatment of acute coronary syndrome because of improvements in efficacy and patient compliance. In this study, the pharmacokinetics of a fixed-dose combination (FDC) of clopidogrel and aspirin was compared with coadministration of individual formulations to clarify the equivalence of the FDC. Methods This was a randomized, open-label, two-period, two-treatment, crossover study in healthy Korean men aged 20–55 years. Subjects received two FDC capsules of clopidogrel/aspirin 75/100 mg (test) or two tablets of clopidogrel 75 mg and two capsules of aspirin 100 mg (reference) with a 14-day washout period. Plasma concentrations of clopidogrel, aspirin, and salicylic acid were measured using validated ultraperformance liquid chromatography–tandem mass spectrometry. Bioequivalence was assessed by analysis of variance and calculation of the 90% confidence intervals (CIs) of the ratios of the geometric means (GMRs) for AUClast and Cmax for clopidogrel and aspirin. Results Sixty healthy subjects were enrolled, and 53 completed the study. Clopidogrel, aspirin, and salicylic acid showed similar absorption profiles and no significant differences in Cmax, AUClast, and Tmax between FDC administration and coadministration of individual formulations. The GMRs (90% CI) for the Cmax and AUClast of clopidogrel were 1.08 (0.95, 1.23) and 0.93 (0.84, 1.03), respectively. The GMRs (90% CI) for the Cmax and AUClast of aspirin were 0.98 (0.84, 1.13) and 0.98 (0.93, 1.04), respectively. Both treatments were well tolerated in the study subjects. Conclusion The FDC of clopidogrel and aspirin was bioequivalent to coadministration of each individual formulation. The FDC capsule exhibited similar safety and tolerability profiles to the individual formulations. Therefore, clopidogrel/aspirin 75 mg/100 mg FDC capsules can be prescribed to improve patient compliance. PMID:27822013

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

    Science.gov (United States)

    Van Gurp, Eveline; Bustamante, Jesus; Franco, Antonio; Rostaing, Lionel; Becker, Thomas; Rondeau, Eric; Czajkowski, Zenon; Rydzewski, Andrzej; Alarcon, Antonio; Bachleda, Petr; Samlik, Jiri; Burmeister, Dirk; Pallardo, Luis; Moal, Marie-Christine; Rutkowski, Boleslaw; Wlodarczyk, Zbigniew

    2010-01-01

    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 (P MMF (P 30 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.

  20. Effect of fixed-dose ACE-inhibitor/calcium channel blocker combination therapy vs. ACE-inhibitor monotherapy on arterial compliance in hypertensive patients with type 2 diabetes.

    Science.gov (United States)

    Winer, Nathaniel; Folker, Amy; Murphy, Julie A; Hung, Elena; Bard, Mara; Perkelvald, Alexander; Sowers, James R; Bakris, George L

    2005-01-01

    Assessment of vascular compliance may be a useful measurement of the clinical effects of antihypertensive treatment. Both angiotensin-converting enzyme (ACE) inhibitors and calcium channel blockers are known to improve vascular elasticity. A study was performed to test the hypothesis that combined therapy with an ACE inhibitor and a calcium channel blocker would have additive benefits on vascular compliance at similar levels of blood pressure (BP), as compared with monotherapy with an ACE inhibitor. This 12-week, double-blind study was a substudy of a larger clinical hypertension study conducted in patients with hypertension and type 2 diabetes. Subjects (N = 20) were randomized to either a fixed-dose combination of amlodipine besylate/benazepril HCl or to enalapril monotherapy. BP, heart rate, large- and small-vessel compliance, systemic vascular resistance, and urinary microalbumin excretion were assessed at baseline and after treatment. Both treatments were similarly effective in lowering BP, reducing systemic vascular resistance, and decreasing urinary microalbumin excretion. Improvement in large-vessel compliance was significantly greater among subjects who received ACE-inhibitor/calcium channel blocker combination therapy (52%) as compared with those who received ACE-inhibitor monotherapy (32%; p < 0.05). No significant change in small-vessel compliance was observed with either treatment. Greater improvement in large-vessel compliance with combination therapy was independent of BP lowering.

  1. A review of the efficacy of fixed-dose combinations olmesartan medoxomil/hydrochlorothiazide and amlodipine besylate/benazepril in factorial design studies.

    Science.gov (United States)

    Quan, Allen; Chavanu, Kathleen; Merkel, Jennifer

    2006-01-01

    In order to adequately control hypertension, the majority of patients will require treatment with more than one antihypertensive agent. Fixed-dose combination therapy offers several advantages, including improved efficacy, tolerability, and treatment compliance. Certain combinations have benefits in specific patient populations, such as the elderly or those with comorbidities. In this review, we evaluate the BP-lowering efficacy of olmesartan medoxomil/hydrochlorothiazide (HCTZ) and amlodipine besylate/benazepril in similarly designed, randomized, placebo-controlled studies in similar patient populations. This indirect comparison showed that both combinations significantly improve both systolic and diastolic BP compared with monotherapy with the individual agents or placebo; it also demonstrated that the combinations were well tolerated. Both combination therapies significantly improved response rates, but olmesartan medoxomil/HCTZ achieved the highest control rates compared with the individual agents. On the basis of an indirect comparison of published factorial design studies, olmesartan medoxomil/HCTZ appears to be at least as effective as amlodipine besylate/benazepril and may provide quantitatively greater reductions in diastolic BP at commonly used dosages. A randomized clinical trial comparing the two combinations is needed to confirm these findings.

  2. Fixed-dose combination of alogliptin/pioglitazone improves glycemic control in Japanese patients with type 2 diabetes mellitus independent of body mass index

    Science.gov (United States)

    Aoki, Chie; Suzuki, Kunihiro; Kuroda, Hisamoto; Sagara, Masaaki; Shimizu, Masanori; Kasai, Kikuo; Aso, Yoshimasa

    2017-01-01

    ABSTRACT This study investigated the effects of switching from combination therapy with either alogliptin (Alo) or pioglitazone (Pio) to fixed-dose combination therapy (FDCT) with alogliptin and pioglitazone (Alo-Pio FDCT). The usefulness and efficacy of Alo-Pio FDCT were investigated. A total of 50 outpatients with type 2 diabetes mellitus (T2DM) treated with Alo and 47 outpatients with T2DM treated with Pio were switched to Alo-Pio FDCT, and its efficacy and usefulness were evaluated. Significant improvements were observed in hemoglobinA1c (HbA1c), alanine transaminase (ALT), and γ-glutamyl transpeptidase (GGT) levels after switching to Alo-Pio FDCT for 16 weeks in both groups. Only the group switching from Alo to Alo-Pio FDCT showed significant improvements in high-density lipoprotein cholesterol (HDL) levels and triglyceride levels. In a multivariate logistic regression model of the variation in the change of HbA1c at 16 weeks, ALT and GGT were independent predictors of the change of HbA1c at 16 weeks. In addition, the switch to Alo-Pio FDCT improved glycemic control to a certain degree regardless of BMI. Switching from either Alo or Pio to Alo-PIO FDCT may, unlike monotherapy with a DPP-4 inhibitor, be effective for patients with T2DM regardless of whether they are obese or lean. PMID:28303056

  3. Low and fixed dose of hydroxyurea is effective and safe in patients with HbSβ(+) thalassemia with IVS1-5(G→C) mutation.

    Science.gov (United States)

    Dehury, Snehadhini; Purohit, Prasanta; Patel, Siris; Meher, Satyabrata; Kullu, Bipin Kishore; Sahoo, Lulup Kumar; Patel, Nayan Kumar; Mohapatra, Alok Kumar; Das, Kishalaya; Patel, Dilip Kumar

    2015-06-01

    Despite compelling evidence that hydroxyurea is safe and effective in sickle cell disease, it is prescribed sparingly due to several barriers like knowledge gaps in certain genotypes, apprehension about its safety and toxicity, and limited resources. We undertook this study to find out the efficacy and safety of HU in patients with HbSβ(+) -thalassemia with IVS1-5(G→C) mutation. We registered 318 patients with HbSβ(+) -thalassemia with IVS1-5(G→C) mutation. Of these, 203 were enrolled for hydroxyurea treatment at a low and fixed dose of 10 mg/kg/day. One hundred four patients (Group-I: 37 children and Group-II: 67 adults) with ≥2 years of hydroxyurea treatment were studied. The rate of vaso-occlusive crises, requirement of blood transfusion and rate of hospitalization reduced from 3 to 0.5, 1 to 0 and 1 to 0 in Group-I and 3 to 0, 1 to 0 and 0.5 to 0 in Group-II respectively after HU therapy (P treatment of patients with HbSβ(+) -thalassemia in resource poor setting. © 2014 Wiley Periodicals, Inc.

  4. Efficacy and safety of fixed-dose losartan/hydrochlorothiazide/amlodipine combination versus losartan/hydrochlorothiazide combination in Japanese patients with essential hypertension.

    Science.gov (United States)

    Rakugi, Hiromi; Tsuchihashi, Takuya; Shimada, Kazuyuki; Numaguchi, Hirotaka; Nishida, Chisato; Yamaguchi, Hiroya; Shirakawa, Masayoshi; Azuma, Kyoichi; Fujita, Kenji P

    2015-01-01

    Japanese patients with uncontrolled essential hypertension received single-blind losartan 50 mg/hydrochlorothiazide 12.5 mg (L50/H12.5) for 8 weeks. Patients whose blood pressure (BP) remained uncontrolled were randomized double-blind to fixed-dose losartan 50 mg/hydrochlorothiazide 12.5 mg/amlodipine 5 mg (L50/H12.5/A5) or L50/H12.5 for 8 weeks followed by open-label L50/H12.5/A5 for 44 weeks. Adverse events were assessed. After 8 weeks, diastolic and systolic BP were reduced significantly more with L50/H12.5/A5 versus L50/H12.5 (both p < 0.001). Mean changes in diastolic and systolic BP were sustained for 44 weeks. L50/H12.5/A5 was well-tolerated and improved BP significantly versus L50/H12.5 in Japanese patients with uncontrolled essential hypertension.

  5. Safety, efficacy and population pharmacokinetics of fixed-dose combination of artesunate-mefloquine in the treatment of acute uncomplicated Plasmodium falciparum malaria in India.

    Science.gov (United States)

    Valecha, Neena; Srivastava, Bina; Dubhashi, N G; Rao, B H Krishnamoorthy; Kumar, Ashwani; Ghosh, S K; Singh, Jai Prakash Narayan; Kiechel, J R; Sharma, Bhawna; Jullien, V; Dash, A P; Taylor, W R J; Anvikar, Anupkumar R

    2013-12-01

    India has switched over to artemisinin-based combination therapy (ACT) for the treatment of acute uncomplicated Plasmodium falciparum malaria and the ACT used in the national programme is artesunate + sulphadoxine-pyrimethamine. Since the efficacy of ACT is dependent also on the partner drug, there is a need to evaluate and deploy multiple ACTs. This multicentre, single-arm, open-label clinical trial was carried out to assess the efficacy, safety and population pharmacokinetics of a fixed dose combination (FDC) artesunate mefloquine (ASMQ) in P. falciparum infected, Indian adults at Panjim, Goa, and Mangalore, Karnataka between December 2007 and November 2008. A total of 77 patients (males 74) were screened and enrolled: 42 at Goa and 35 at Mangalore with a median age of 25 yr (range 18-55 yr). One patient failed in treatment on D53, a PCR proven new infection, seven developed recurrent vivax parasitaemia and 11 did not have a parasitological endpoint. By per protocol analysis, the D63 cure rate was 58/59 (98.3; 95% C.I. 90.9-99.9%), and 58/58, with PCR correction. ASMQ was well-tolerated and no serious adverse events were reported. The study showed that the ASMQ FDC was efficacious and well-tolerated for the treatment of acute, uncomplicated P. falciparum malaria in highly endemic, chloroquine resistant areas of Goa and Mangalore. It is a viable option for India.

  6. The Effect on Treatment Adherence of Administering Drugs as Fixed-Dose Combinations versus as Separate Pills: Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Katy A. van Galen

    2014-01-01

    Full Text Available Administering drugs as fixed-dose combinations (FDCs versus the same active drugs administered as separate pills is assumed to enhance treatment adherence. We synthesized evidence from randomized controlled trials (RCTs about the effect of FDCs versus separate pills on adherence. We searched PubMed for RCTs comparing a FDC with the same active drugs administered as separate pills, including a quantitative estimate of treatment adherence, without restriction to medical condition. The odds ratio (OR of optimal adherence with FDCs versus separate pills was used as common effect size and aggregated into a pooled effect estimate using a random effect model with inverse variance weights. Out of 1258 articles screened, only six studies fulfilled inclusion criteria. Across medical conditions, administering drugs as FDC significantly increased the likelihood of optimal adherence (OR 1.33 (95% CI, 1.03–1.71. Within subgroups of specific medical conditions, the favourable effect of FDCs on adherence was of borderline statistical significance for HIV infection only (OR 1.46 (95% CI, 1.00–2.13. We observed a remarkable paucity of RCTs comparing the effect on adherence of administering drugs as FDC versus as separate pills. Administering drugs as FDC improved medication adherence. However, this conclusion is based on a limited number of RCTs only.

  7. The Effect on Treatment Adherence of Administering Drugs as Fixed-Dose Combinations versus as Separate Pills: Systematic Review and Meta-Analysis.

    Science.gov (United States)

    van Galen, Katy A; Nellen, Jeannine F; Nieuwkerk, Pythia T

    2014-01-01

    Administering drugs as fixed-dose combinations (FDCs) versus the same active drugs administered as separate pills is assumed to enhance treatment adherence. We synthesized evidence from randomized controlled trials (RCTs) about the effect of FDCs versus separate pills on adherence. We searched PubMed for RCTs comparing a FDC with the same active drugs administered as separate pills, including a quantitative estimate of treatment adherence, without restriction to medical condition. The odds ratio (OR) of optimal adherence with FDCs versus separate pills was used as common effect size and aggregated into a pooled effect estimate using a random effect model with inverse variance weights. Out of 1258 articles screened, only six studies fulfilled inclusion criteria. Across medical conditions, administering drugs as FDC significantly increased the likelihood of optimal adherence (OR 1.33 (95% CI, 1.03-1.71)). Within subgroups of specific medical conditions, the favourable effect of FDCs on adherence was of borderline statistical significance for HIV infection only (OR 1.46 (95% CI, 1.00-2.13)). We observed a remarkable paucity of RCTs comparing the effect on adherence of administering drugs as FDC versus as separate pills. Administering drugs as FDC improved medication adherence. However, this conclusion is based on a limited number of RCTs only.

  8. Single-session intense pulsed light combined with stable fixed-dose triple combination topical therapy for the treatment of refractory melasma.

    Science.gov (United States)

    Figueiredo Souza, Linton; Trancoso Souza, Simone

    2012-01-01

    The effectiveness of intense pulsed light (IPL) has been reported in adults with melasma, but there is little information about IPL with triple combination topical therapy (TC) and refractory melasma. Sixty-two patients with totally or partially refractory melasma were enrolled in this randomized open-label study. Thirty-one patients were treated with IPL in a single session, bleaching agents and broad-spectrum sunscreens. Thirty-one patients were in the control group, receiving only bleaching agents and broad-spectrum sunscreens. The Melasma Area and Severity Index (MASI) and the investigator's global assessment using a seven-point scale were used to determine the impact and effectiveness of the treatment. The IPL group results based on MASI showed a 49.4% reduction (from 17.6 to 8.9; p group and control group was significant (p = 0.002), with a better response in the IPL group. Single session IPL combined with stable fixed-dose triple combination treatment is a safe and effective treatment for refractory mixed and dermal melasma.

  9. Fixed-dose combination of alogliptin/pioglitazone improves glycemic control in Japanese patients with type 2 diabetes mellitus independent of body mass index.

    Science.gov (United States)

    Aoki, Chie; Suzuki, Kunihiro; Kuroda, Hisamoto; Sagara, Masaaki; Shimizu, Masanori; Kasai, Kikuo; Aso, Yoshimasa

    2017-02-01

    This study investigated the effects of switching from combination therapy with either alogliptin (Alo) or pioglitazone (Pio) to fixed-dose combination therapy (FDCT) with alogliptin and pioglitazone (Alo-Pio FDCT). The usefulness and efficacy of Alo-Pio FDCT were investigated. A total of 50 outpatients with type 2 diabetes mellitus (T2DM) treated with Alo and 47 outpatients with T2DM treated with Pio were switched to Alo-Pio FDCT, and its efficacy and usefulness were evaluated. Significant improvements were observed in hemoglobinA1c (HbA1c), alanine transaminase (ALT), and γ-glutamyl transpeptidase (GGT) levels after switching to Alo-Pio FDCT for 16 weeks in both groups. Only the group switching from Alo to Alo-Pio FDCT showed significant improvements in high-density lipoprotein cholesterol (HDL) levels and triglyceride levels. In a multivariate logistic regression model of the variation in the change of HbA1c at 16 weeks, ALT and GGT were independent predictors of the change of HbA1c at 16 weeks. In addition, the switch to Alo-Pio FDCT improved glycemic control to a certain degree regardless of BMI. Switching from either Alo or Pio to Alo-PIO FDCT may, unlike monotherapy with a DPP-4 inhibitor, be effective for patients with T2DM regardless of whether they are obese or lean.

  10. The efficacy and safety of initial use of irbesartan/hydrochlorothiazide fixed-dose combination in hypertensive patients with and without high cardiovascular risk.

    Science.gov (United States)

    Weir, Matthew R; Neutel, Joel M; Bhaumik, Amitabha; De Obaldia, Maria Elena; Lapuerta, Pablo

    2007-12-01

    A post hoc pooled analysis of 2 multicenter, randomized, double-blind, active-controlled force-titration studies assessed the antihypertensive efficacy and tolerability of 7 to 8 weeks' once-daily fixed-dose irbesartan/hydrochlorothiazide (HCTZ) 300/25 mg in 796 stage 1 or 2 hypertensive patients according to age (65 years or older or younger than 65) (n=121 or 675) and presence or absence of obesity (n=378 or 414), type 2 diabetes (n=99 or 697), and high World Health Organization-defined cardiovascular risk (n=593 or 202). Systolic/diastolic blood pressure reductions (27-31/16-22 mm Hg) were similar regardless of age, obesity, and type 2 diabetes status and were greater in high- vs low-risk patients. Dizziness (2.0%-3.7%), hypotension (0%-0.7%), and syncope (0%) were rare and not centered in any subgroup. There was no hypotension in the elderly or in type 2 diabetics. Irbesartan/HCTZ provided consistent blood pressure lowering and tolerability regardless of age, obesity, and type 2 diabetes and greater efficacy in patients with high cardiovascular risk.

  11. Chemical interactions study of antiretroviral drugs efavirenz and lamivudine concerning the development of stable fixed-dose combination formulations for AIDS treatment

    Energy Technology Data Exchange (ETDEWEB)

    Gomes, Elionai C. de L.; Mussel, Wagner N.; Resende, Jarbas M.; Yoshida, Maria I., E-mail: mirene@ufmg.br [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Instituto de Ciencias Exatas. Departamento de Quimica; Fialho, Silvia L.; Barbosa, Jamile; Fialho, Silvia L. [Fundacao Ezequiel Dias, Belo Horizonte, MG (Brazil)

    2013-04-15

    Lamivudine and efavirenz are among the most worldwide used drugs for acquired immune deficiency syndrome (AIDS) treatment. Solid state nuclear magnetic resonance (ssNMR), Fourier-transformed infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and thermo-optical analysis (TOA) were used to study possible interactions between these drugs, aiming the development of a fixed-dose drug combination. DSC and TOA have evidenced significant shifts on the melting points of both drugs in the mixture, which may be due to interaction between them. Although DSC and TOA results indicated incompatibility between the drugs, FTIR spectra were mostly unmodified due to overlapping peaks. The ssNMR analyses showed significant changes in chemical shifts values of the mixture when compared with spectra of pure drugs, especially in the signals relating to the deficient electron carbon atoms of both drugs. These results confirm the interactions suggested by DSC and TOA, which is probably due to acid-base interactions between electronegative and deficient electron atoms of both lamivudine and efavirenz. (author)

  12. The content of African diets is adequate to achieve optimal efficacy with fixed-dose artemether-lumefantrine: a review of the evidence

    Directory of Open Access Journals (Sweden)

    Sagara Issaka

    2008-11-01

    Full Text Available Abstract A fixed-dose combination of artemether-lumefantrine (AL, Coartem® has shown high efficacy, good tolerability and cost-effectiveness in adults and children with uncomplicated malaria caused by Plasmodium falciparum. Lumefantrine bioavailability is enhanced by food, particularly fat. As the fat content of sub-Saharan African meals is approximately a third that of Western countries, it raises the question of whether fat consumption by African patients is sufficient for good efficacy. Data from healthy volunteers have indicated that drinking 36 mL soya milk (containing only 1.2 g of fat results in 90% of the lumefantrine absorption obtained with 500 mL milk (16 g fat. African diets are typically based on a carbohydrate staple (starchy root vegetables, fruit [plantain] or cereals supplemented by soups, relishes and sauces derived from vegetables, pulses, nuts or fish. The most important sources of dietary fat in African countries are oil crops (e.g. peanuts, soya beans and cooking oils as red palm, peanut, coconut and sesame oils. Total fat intake in the majority of subSaharan countries is estimated to be in the range 30–60 g/person/day across the whole population (average 43 g/person/day. Breast-feeding of infants up to two years of age is standard, with one study estimating a fat intake of 15–30 g fat/day from breast milk up to the age of 18 months. Weaning foods typically contain low levels of fat, and the transition from breast milk to complete weaning is associated with a marked reduction in dietary fat. Nevertheless, fat intake >10 g/day has been reported in young children post-weaning. A randomized trial in Uganda reported no difference in the efficacy of AL between patients receiving supervised meals with a fixed fat content (~23 g fat or taking AL unsupervised, suggesting that fat intake at home was sufficient for optimal efficacy. Moreover, randomized trials in African children aged 5–59 months have shown similar high cure

  13. Efficacy of indacaterol 75 µg versus fixed-dose combinations of formoterol-budesonide or salmeterol-fluticasone for COPD: a network meta-analysis

    Directory of Open Access Journals (Sweden)

    Cope S

    2012-07-01

    Full Text Available Shannon Cope,1 Matthias Kraemer,2 Jie Zhang,3 Gorana Capkun-Niggli,2 Jeroen P Jansen11MAPI Consultancy, Boston, MA, USA; 2Novartis Pharmaceuticals, Basel, Switzerland; 3Novartis Pharmaceuticals, East Hanover, NJ, USABackground: The purpose of this study was to update our network meta-analysis in order to compare the efficacy of indacaterol 75 µg with that of a fixed-dose combination of formoterol and budesonide (FOR/BUD and a fixed-dose combination salmeterol and fluticasone (SAL/FP for the treatment of chronic obstructive pulmonary disease (COPD based on evidence identified previously in addition to two new randomized clinical trials.Methods: Fifteen randomized, placebo-controlled clinical trials including COPD patients were evaluated: indacaterol 75 µg once daily (n = 2 studies, indacaterol 150 µg once daily (n = 5, indacaterol 300 µg once daily (n = 4, FOR/BUD 9/160 µg twice daily (n = 2, FOR/BUD 9/320 µg twice daily (n = 2, SAL/FP 50/500 µg twice daily (n = 4, and SAL/FP 50/250 µg twice daily (n = 1. All trials were analyzed simultaneously using a Bayesian network meta-analysis and relative treatment effects between all regimens were obtained. Treatment-by-covariate interactions were included where possible to improve the similarity of the trials. Outcomes of interest were trough forced expiratory volume in 1 second (FEV1 and transitional dyspnea index at 12 weeks.Results: Based on the results without adjustment for covariates, indacaterol 75 µg resulted in a greater improvement in FEV1 at 12 weeks compared with FOR/BUD 9/160 µg (difference in change from baseline 0.09 L [95% credible interval 0.04–0.13] and FOR/BUD 9/320 µg (0.07 L [0.03–0.11] and was comparable with SAL/FP 50/250 µg (0.00 L [-0.07–0.07] and SAL/FP 50/500 µg (0.01 L [-0.04–0.05]. For transitional dyspnea index, data was available only for indacaterol 75 µg versus SAL/FP 50/500 µg (-0.49 points [-1.87–0.89].Conclusion: Based on results of a network

  14. A Stability-Indicating High Performance Liquid Chromatographic Assay for the Simultaneous Determination of Pyridoxine, Ethionamide, and Moxifloxacin in Fixed Dose Combination Tablets

    Directory of Open Access Journals (Sweden)

    Munib-ur-Rehman

    2014-01-01

    Full Text Available Stability indicating reversed phase HPLC method was developed and validated for the simultaneous quantitation of antitubercular drugs, ethionamide (ETH, and moxifloxacin (MOX with commonly coprescribed vitamin, pyridoxine (PYR in tablet dosage form. The method was found rapid, precise and accurate. The separation was performed in Hibar 150-4.6, Purospher STAR, RP-18e (5 μm column, using mobile phase A (0.03 M sodium citrate adjusted to pH 5 with glacial acetic acid and mobile phase B (100% methanol, ran at variable proportions at flow rate of 1.0 mL/min. The detection was carried out at 320 nm. The method was observed linearly in the range of 2.5–17.5 μg/mL for PYR, 25–175 μg/mL for ETH, and 40–280 μg/mL for MOX with respective limits of detection/quantitation of 0.125 μg/mL/1.28 μg/mL, 0.25 μg/mL/2.56 μg/mL, and 0.35 μg/mL/3.65 μg/mL. The drugs were also subjected to oxidative, hydrolytic, photolytic, and thermal degradation; the degradation products showed interference with the detection of PYR, ETH, and MOX. The proposed method was observed to be effective to quantitate MOX (400 mg, ETH (250 mg, and PYR (25 mg in fixed dose combination tablet formulation.

  15. Legal, ethical, and economic implications of breaking down once-daily fixed-dose antiretroviral combinations into their single components for cost reduction.

    Science.gov (United States)

    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.

  16. Reversed phase-high performance liquid chromatographic method for simultaneous estimation of tolperisone hydrochloride and etodolac in a combined fixed dose oral formulations.

    Science.gov (United States)

    Patel, Mit J; Badmanaban, R; Patel, C N

    2011-04-01

    A reversed-phase liquid chromatographic (RP-HPLC) method was developed for the simultaneous determination of tolperisone hydrochloride (TOLP) and etodolac (ETD) in a combined fixed dose oral formulation. The analysis was carried out using a phenomenax C-18, pre-packed column. A mobile phase containing a phosphate buffer (pH 5.5) : Methanol : Acetonitrile : Tri-ethylamine (40 : 40 : 20 : 1.5), with the pH adjusted to orthophosphoric acid, was pumped at a flow rate of 1.0 ml min(1) with a UV-detector and PDA detection at 257 nm. Retention time was 3.91 minutes and 6.89 minutes for TOLP and ETD, respectively. The method was validated for linearity, accuracy, precision, sensitivity, and specificity. The method showed good linearity in the range of 3 - 21 μg ml for TOLP μg / ml and 8 - 56 μg / ml for ETD. The detection limit of the proposed method was 0.16 μg / ml and 0.58 μg / ml for TOLP and ETD, respectively. The quantification limit of the proposed method was 0.51 μg / ml and 1.7 μg / ml for TOLP and ETD, respectively. The % recovery was within the range of 99.42 - 101.15 for TOLP and 98.63 - 100.94 for ETD. The percentage RSD for precision of the method was found to be less than 2%. The method was validated as per the International Conference on Harmonization (ICH) guidelines. The developed method could be applied for routine analysis of TOLP and ETD in tablet dosage form.

  17. Comparisons of the pharmacokinetics and tolerability of fixed-dose combinations of amlodipine besylate/losartan and amlodipine camsylate/losartan in healthy subjects: a randomized, open-label, single-dose, two-period, two-sequence crossover study

    Science.gov (United States)

    Choi, YoonJung; Lee, SeungHwan; Cho, Sang-Min; Kang, Won-Ho; Nam, Kyu-Yeol; Jang, In-Jin; Yu, Kyung-Sang

    2016-01-01

    Background A fixed-dose combination (FDC) of amlodipine and losartan has been used to reduce blood pressure in patients whose hypertension is not sufficiently controlled with either drug alone. The aim of this study was to evaluate the pharmacokinetic (PK) characteristics and tolerability of an FDC of 6.94 mg amlodipine besylate (5 mg as amlodipine)/50 mg losartan potassium compared to an FDC of 5 mg amlodipine camsylate/50 mg losartan potassium in healthy subjects. Subjects and methods A randomized, open-label, single-dose, two-period, two-sequence crossover study was conducted on 46 healthy male subjects. Blood concentrations were measured by liquid chromatography–tandem mass spectrometry. Blood samples were collected up to 144 hours post dose for each period. PK parameters were calculated in each treatment group using a noncompartmental method. The 90% confidence intervals (CIs) of the geometric mean ratios of the two treatments for the maximum plasma concentration (Cmax) and the area under the concentration curve from time zero to the last quantifiable time point (AUC0–t) were estimated. Tolerability assessments were performed for all subjects who received the drug at least once. Results The PK profiles of the two treatments were similar. For amlodipine, the geometric mean ratios (90% CIs) of amlodipine besylate to amlodipine camsylate for the Cmax and AUC0–t were 0.98 (0.94−1.01) and 0.97 (0.93−1.01), respectively. The corresponding values for losartan were 0.91 (0.81−1.02) and 1.05 (0.98−1.12), respectively. The incidence of adverse events was not significantly different between the two treatments, and both were well tolerated. Conclusion An FDC of 6.94 mg amlodipine besylate (5 mg as amlodipine)/50 mg losartan potassium produced similar results to an FDC of 5 mg amlodipine camsylate/50 mg losartan potassium treatment with respect to the PK parameters of amlodipine and losartan based on Cmax and AUC0–t values. The amlodipine besylate

  18. A fixed-dose combination tablet of gemigliptin and metformin sustained release has comparable pharmacodynamic, pharmacokinetic, and tolerability profiles to separate tablets in healthy subjects

    Directory of Open Access Journals (Sweden)

    Park SI

    2015-02-01

    Full Text Available Sang-In Park,1,* Howard Lee,1,2,* Jaeseong Oh,1 Kyoung Soo Lim,3 In-Jin Jang,1 Jeong-Ae Kim,4 Jong Hyuk Jung,4 Kyung-Sang Yu1 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, 2Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Clinical Trials Center, Seoul National University Hospital, Seoul, 3Department of Clinical Pharmacology and Therapeutics, CHA University School of Medicine and CHA Bundang Medical Center, Seongnam, 4LG Life Sciences, Ltd, Seoul, Republic of Korea *These authors contributed equally to this work Background: In type 2 diabetes mellitus, fixed-dose combination (FDC can provide the complementary benefits of correction of multiple pathophysiologic defects such as dysfunctions in glycemic or metabolic control while improving compliance compared with separate tablets taken together. The objective of the study reported here was to compare the pharmacodynamic (PD, pharmacokinetic (PK, and tolerability profiles of gemigliptin and extended-release metformin (metformin XR between FDC and separate tablets.Methods: A randomized, open-label, single-dose, two-way, two-period, crossover study was conducted in 28 healthy male volunteers. Two FDC tablets of gemigliptin/metformin 25/500 mg or separate tablets of gemigliptin (50 mg ×1 and metformin XR (500 mg ×2 were orally administered in each period. Serial blood samples were collected up to 48 hours post-dose to determine dipeptidyl peptidase 4 (DPP-4 activity using spectrophotometric assay and concentrations of gemigliptin and metformin using tandem mass spectrometry. Geometric mean ratios (GMRs of FDC to separate tablet formulations and their 90% confidence intervals (CIs were calculated to compare the PD and PK parameters between the two formulations. Tolerability was assessed throughout the study.Results: The plasma DPP-4 activity

  19. Evaluation of efficacy and safety of fixed dose lovastatin and niacinER combination in Asian Indian dyslipidemic patients: a multicentric study

    Directory of Open Access Journals (Sweden)

    Manoj Sharma

    2006-03-01

    Full Text Available Manoj Sharma1, Deepika R Sharma1, Vikram Singh1, RB Panwar2, HS Hira3, Bishav Mohan4, Naveen Kumar4, SK Sharma5, Rajeev Gupta61Clinical Research Division, Panacea-Biotec Ltd, New Delhi; 2SP Medical College, Bikaner; 3Maulana Azad Medical College, New Delhi; 4Dayanand Medical College, Ludhiana; 5SMS Medical College, Jaipur; 6Monilek Hospital and Research Center, Jaipur, India.Abstract: Asian Indian dyslipidemia is characterized by: borderline high low-density lipoprotein (LDL cholesterol and apolipoprotein (apo B; high triglycerides, low high-density lipoprotein (HDL cholesterol and apoA1; and high lipoprotein(a (lp[a]. We performed a controlled multicentric trial in India to evaluate the efficacy and safety of a fixed dose combination of lovastatin and niacin extended release (niacinER formulation in patients with moderate to severe dyslipidemia. Consecutive subjects that satisfied the selection criteria, agreed to an informed consent, and with no baseline presence of liver/renal disease or heart failure were enrolled in the study. After a 4-week run-in period there were 142 patients with LDL levels ≥ 130 mg/dL. Eleven patients were excluded because of uncontrolled hyperglycemia and 131 patients were recruited. After baseline evaluation of clinical and biochemical parameters all subjects were administered lovastatin (20 mg and niacinER (500 mg combination once daily. Dose escalation was done on basis of lipid parameters at 8 weeks and in 11 patients increased to lovastatin (20 mg and niacinER (1000 mg. An intention-to-treat analysis was performed and data was analyzed using nonparametric Wilcoxon signed rank test. Thirteen patients (10% were lost to follow-up and 4 (3% withdrew because of dermatological adverse effects: flushing, pruritus, and rash. The mean values of various lipid parameters (mg/dL at baseline, and at weeks 4, 12, and 24 respectively were: total cholesterol 233.9 ± 27, 206.3 ± 27, 189.8 ± 31, and 174.9 ± 27 mg/dL; LDL

  20. Cost-effectiveness and budget impact of the fixed-dose dual bronchodilator combination tiotropium–olodaterol for patients with COPD in the Netherlands

    Directory of Open Access Journals (Sweden)

    van Boven JF

    2016-09-01

    Full Text Available Job FM van Boven,1,2 Janwillem WH Kocks,2 Maarten J Postma1,3,4 1Department of Pharmacy, Unit of PharmacoEpidemiology & PharmacoEconomics, 2Department of General Practice, Groningen Research Institute for Asthma and COPD (GRIAC, 3Institute of Science in Healthy Aging & healthcaRE (SHARE, 4Department of Epidemiology, University Medical Center Groningen (UMCG, University of Groningen, Groningen, the Netherlands Purpose: The fixed-dose dual bronchodilator combination (FDC of tiotropium and olodaterol showed increased effectiveness regarding lung function and health-related quality of life in patients with chronic obstructive pulmonary disease (COPD compared with the use of its mono-components. Yet, while effectiveness and safety have been shown, the health economic implication of this treatment is still unknown. The aim of this study was to assess the cost–utility and budget impact of tiotropium–olodaterol FDC in patients with moderate to very severe COPD in the Netherlands.Patients and methods: A cost–utility study was performed, using an individual-level Markov model. To populate the model, individual patient-level data (age, height, sex, COPD duration, baseline forced expiratory volume in 1 second were obtained from the tiotropium–olodaterol TOnado trial. In the model, forced expiratory volume in 1 second and patient-level data were extrapolated to utility and survival, and treatment with tiotropium–olodaterol FDC was compared with tiotropium. Cost–utility analysis was performed from the Dutch health care payer’s perspective using a 15-year time horizon in the base-case analysis. The standard Dutch discount rates were applied (costs: 4.0%; effects: 1.5%. Both univariate and probabilistic sensitivity analyses were performed. Budget impact was annually assessed over a 5-year time horizon, taking into account different levels of medication adherence.Results: As a result of cost increases, combined with quality-adjusted life-year (QALY

  1. Long-term efficacy and tolerability of a fixed-dose combination of antihypertensive agents: an open-label surveillance study in China.

    Science.gov (United States)

    Wu, Yiqun; Hu, Yonghua; Tang, Xun; He, Liu; Ren, Tao; Tao, Qiushan; Qin, Xueying; Sun, Ningling; Wang, Hongyi; Cao, Weihua; Wu, Tao; Zhan, Siyan; Wang, Jin; Chen, Weihua; Li, Liming

    2011-11-01

    A fixed-dose combination (FDC) of four compounds, hydrochlorothiazide 12.5 mg, triamterene 12.5 mg, dihydralazine 12.5 mg and reserpine 0.1 mg (HTDR), is widely used as an antihypertensive treatment in China. Although HTDR has been used in China for more than 30 years, there have been few comprehensive evaluations of this treatment. The aim of this study was to investigate the long-term efficacy and tolerability of HTDR in Chinese patients with essential hypertension. This was a 36-month, community-based, open-label surveillance study, conducted in the Huangpu District (Shanghai, China). The study was based in local primary healthcare settings. Subjects were recruited if they had essential hypertension, were aged ≥35 years at the time of enrolment, were expected to remain in the area for 3 years, and were able to provide informed consent. Patients who had secondary hypertension, myocardial infarction or stroke within 6 months of screening, impaired renal or hepatic function, history of cardiomyopathy or chronic heart failure, or were pregnant or lactating were excluded. HTDR was administered as one or two tablets per day in the morning. If necessary, additional hydrochlorothiazide was added. Blood pressure (BP) was measured at baseline and throughout the 36-month surveillance period every 3 months. Biochemical indicators (e.g. fasting blood glucose, plasma lipid parameters, plasma sodium and potassium, plasma uric acid and serum creatinine) were also measured, and adverse events were noted. BP reductions and the rate at which patients achieved BP targets (systolic BP [SBP] treatment period, 93.1% of patients had achieved the SBP target, 97.9% had achieved the DBP target, and 92.1% had achieved both. The mean decreases in SBP and DBP were 15.3 mmHg and 9.9 mmHg, respectively. Overall, 127 adverse events in 119 patients (7.8%) occurred during the follow-up period, most of which were mild to moderate. Plasma lipid profiles were improved after 24 months of treatment

  2. [Influence of compliance on the incidence of cardiovascular events and health costs when using single-pill fixed-dose combinations for the treatment of hypertension].

    Science.gov (United States)

    Sicras Mainar, Antoni; Galera Llorca, Jordi; Muñoz Ortí, Genís; Navarro Artieda, Ruth

    2011-02-26

    .001). Better compliance and persistence with antihypertensive fixed-dose combinations improves therapeutic control, leading to a significant reduction of cerebrovascular accidents and total health care costs. Copyright © 2009 Elsevier España, S.L. All rights reserved.

  3. What strategies to boost production of affordable fixed-dose anti-retroviral drug combinations for children in the developing world?

    Science.gov (United States)

    Dionisio, Daniele; Gass, Robert; McDermott, Peter; Racalbuto, Vincenzo; Madeo, Marina; Braghieri, Giuseppe; Crowley, Siobhan; Pinheiro, Eloan Dos Santos; Graaff, Peter; Vasan, Ashwin; Eksaengsri, Achara; Moller, Helene; Khanna, Arun Kumar; Kraisintu, Krisana; Juneja, Sandeep; Nicolaou, Stavros; Sengupta, Aloka; Esperti, Francesco; Messeri, Daniela

    2007-03-01

    No more than 8% of HIV positive children needing treatment in low- and middle-income countries have access to antiretroviral drugs (ARVs). Children presently account for about 4% of all treated patients, while for equitable access they should make up at least 13%. This study explores key issues, implications and interaction dynamics to boost production of easy-to-use and affordable fixed-dose combination (FDC) ARVs for children in the developing world. Potentials for equitable solutions are examined including priority steps and actions, appropriate treatment options and reliable forecasting methods for paediatric ARVs, as well as combination incentives to generic companies against market unattractiveness and enforced intellectual property (IP) rights. Moreover, implementation strategies to enhance the development and production of affordable ARV paediatric formulations and appropriate supply systems to ensure availability are investigated. The current market for FDC paediatric ARVs is already substantial and will only grow with improved and scaled up diagnosis and monitoring of children. This provides an argument for immediate increase of production and development of FDC ARVs for children. These formulations must be low cost and included in the list of Essential Medicines to avoid children continuing to lag behind in access to treatment. Access-oriented, long-term drug policy strategies with the ability to pass muster of governments, the UN system, as well as generic and research-based enterprises are needed to let children gain expanded and sustained access to FDC ARVs. Under the requirements listed above, IP-bound Voluntary License (VL) flexibilities do appear, if coupled with substantial combination incentives to generic firms, as a fitting tool into the needs. Policies must consider enhancing human resource capacity in the area of caregivers and social and health workers aiming to spread correct information and awareness on effectiveness and rationale of FDC

  4. 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 *

    OpenAIRE

    Ferreira, Anna Carolina Galvão; da Silva, José Laerte Rodrigues; Conde, Marcus Barreto; Rabahi, Marcelo Fouad

    2013-01-01

    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 s...

  5. To compare the efficacy and safety of fixed dose combination of thiocolchicoside and aceclofenac versus chlorzoxazone, aceclofenac and paracetamol in patients with acute lower backache associated with muscle spasm

    OpenAIRE

    Kumar, Sanjeev; Rani, Seema; Siwach, Ramchander; Verma, Prem

    2014-01-01

    Background: The fixed dose combinations (FDCs) of muscle relaxants, non-steroidal anti-inflammatory drugs and paracetamol are commonly prescribed in the treatment of acute lower backache. Aim: The present study was undertaken with the aim of comparing the efficacy and safety of FDCs of thiocolchicoside and aceclofenac versus chlorzoxazone, aceclofenac and paracetamol in patients with acute lower backache associated with muscle spasm. Materials and Methods: A total of 100 patients between ages...

  6. Comparisons of the pharmacokinetics and tolerability of fixed-dose combinations of amlodipine besylate/losartan and amlodipine camsylate/losartan in healthy subjects: a randomized, open-label, single-dose, two-period, two-sequence crossover study

    Directory of Open Access Journals (Sweden)

    Choi Y

    2016-09-01

    Full Text Available YoonJung Choi,1 SeungHwan Lee,2 Sang-Min Cho,3 Won-Ho Kang,3 Kyu-Yeol Nam,4 In-Jin Jang,1 Kyung-Sang Yu1 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine, 2Clinical Trials Center, Seoul National University Hospital, 3Research Institute, 4Global R&D, Korea United Pharm Inc., Seoul, Republic of Korea Background: A fixed-dose combination (FDC of amlodipine and losartan has been used to reduce blood pressure in patients whose hypertension is not sufficiently controlled with either drug alone. The aim of this study was to evaluate the pharmacokinetic (PK characteristics and tolerability of an FDC of 6.94 mg amlodipine besylate (5 mg as amlodipine/50 mg losartan potassium compared to an FDC of 5 mg amlodipine camsylate/50 mg losartan potassium in healthy subjects. Subjects and methods: A randomized, open-label, single-dose, two-period, two-sequence crossover study was conducted on 46 healthy male subjects. Blood concentrations were measured by liquid chromatography–tandem mass spectrometry. Blood samples were collected up to 144 hours post dose for each period. PK parameters were calculated in each treatment group using a noncompartmental method. The 90% confidence intervals (CIs of the geometric mean ratios of the two treatments for the maximum plasma concentration (Cmax and the area under the concentration curve from time zero to the last quantifiable time point (AUC0–t were estimated. Tolerability assessments were performed for all subjects who received the drug at least once. Results: The PK profiles of the two treatments were similar. For amlodipine, the geometric mean ratios (90% CIs of amlodipine besylate to amlodipine camsylate for the Cmax and AUC0–t were 0.98 (0.94-1.01 and 0.97 (0.93-1.01, respectively. The corresponding values for losartan were 0.91 (0.81-1.02 and 1.05 (0.98-1.12, respectively. The incidence of adverse events was not significantly different between the two

  7. Enhanced Weight based DSR for Mobile Ad Hoc Networks

    Science.gov (United States)

    Verma, Samant; Jain, Sweta

    2011-12-01

    Routing in ad hoc network is a great problematic, since a good routing protocol must ensure fast and efficient packet forwarding, which isn't evident in ad hoc networks. In literature there exists lot of routing protocols however they don't include all the aspects of ad hoc networks as mobility, device and medium constraints which make these protocols not efficient for some configuration and categories of ad hoc networks. Thus in this paper we propose an improvement of Weight Based DSR in order to include some of the aspects of ad hoc networks as stability, remaining battery power, load and trust factor and proposing a new approach Enhanced Weight Based DSR.

  8. 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.

    Science.gov (United States)

    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

  9. Effects of roflumilast in COPD patients receiving inhaled corticosteroid/long-acting β2-agonist fixed-dose combination: RE2SPOND rationale and study design

    Directory of Open Access Journals (Sweden)

    Rennard SI

    2016-08-01

    Full Text Available Stephen I Rennard,1,2 Fernando J Martinez,3,4 Klaus F Rabe,5–7 Sanjay Sethi,8 Emilio Pizzichini,9 Andrew McIvor,10 Shahid Siddiqui,11 Antonio Anzueto,12 Haiyuan Zhu13 1Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA; 2AstraZeneca, Cambridge, UK; 3Joan and Sanford I Weill Department of Medicine, Weill Cornell University, New York, NY, 4Department of Internal Medicine, Michigan Health System, Ann Arbor, MI, USA; 5LungenClinic Grosshansdorf, Großhansdorf, 6Department of Medicine, University Kiel, Kiel, 7Airway Research Center North, German Center for Lung Research, Großhansdorf, Germany; 8Department of Medicine, University at Buffalo, State University of New York, Buffalo, NY, USA; 9Department of Medicine, Universidade Federal de Santa Catarina, Santa Catarina, Brazil; 10Firestone Institute of Respiratory Health, St Joseph’s Healthcare, McMaster University, Hamilton, ON, Canada; 11AstraZeneca, Gaithersburg, MD, 12South Texas Veterans Health Care System at San Antonio, University of Texas Health Science Center, San Antonio, TX, 13Allergan plc, Jersey City, NJ, USA Background: Roflumilast, a once-daily, selective phosphodiesterase-4 inhibitor, reduces the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations. The RE2SPOND study is examining whether roflumilast, when added to an inhaled corticosteroid/long-acting β2-agonist (ICS/LABA fixed-dose combination (FDC, further reduces exacerbations. The methodology is described herein. Methods: In this Phase IV, multicenter, double-blind, placebo-controlled, parallel-group trial, participants were randomized 1:1 (stratified by long-acting muscarinic antagonist use to receive roflumilast or placebo, plus ICS/LABA FDC, for 52 weeks. Eligible participants had severe COPD associated with chronic bronchitis, had two or more moderate–severe exacerbations within 12 months, and were receiving ICS

  10. Determinants of use of the fixed dose combination emtricitabine/rilpivirine/tenofovir (Eviplera in HIV-infected persons receiving care in Italy

    Directory of Open Access Journals (Sweden)

    Alessandro Cozzi-Lepri

    2014-11-01

    Full Text Available Introduction: Emtricitabine/rilpivirine/tenofovir (EVP is a fixed-dose combination of antiretrovirals (ARV approved by the European Medicines Agency in November 2011 and introduced in Italy in February 2013. It is a once-a-day single tablet and is licensed in Europe for use only in ARV-naïve patients with a viral load (VL ≤100,000 copies/mL. Objective: To identify factors that may be associated with the use of EVP as first-line regimen in HIV-infected individuals starting cART from ARV-naïve in Italy. Methods: Clinical sites in ICONA Foundation Study in which ≥1 person had started EVP were selected for this analysis. From these we included all patients who started an EVP-based cART regimen as well as those starting other cART regimens after the date of introduction of EVP at the site (after February 2013 in any case and with a VL ≤100,000 copies/mL from ARV-naïve. Characteristics at the time of starting cART were compared using chi-square test and unadjusted and adjusted logistic regression analysis. Factors investigated included: gender, mode of HIV transmission, time from HIV diagnosis, CD4 count, nation of birth, AIDS, HCV-status, age, CD8 count, VL, diabetes, smoking, total and HDL cholesterol, eGFR, blood glucose, level of education and employment and site location. Factors showing unadjusted associations with a p-value of 10% or smaller, were retained in the multivariable model. Results: We identified 183 patients starting EVP and 173 starting the control regimen from 23 sites. The number of patients starting EVP included at each site ranged from 1 to 12 and the number of those starting the control regimen was similar. The most frequently used drugs in the concurrent group were: TDF (75%, FTC (74%, DRV (39%, ATV/r (26%, LPV/r (9%, EFV (13% and RAL (14%. In univariable analysis, there were differences in median CD4 count (390 cells/mm3 in EVP versus 348 in controls, p=0.002, time from HIV diagnosis to starting cART (11 versus 3

  11. Fix 40!

    Index Scriptorium Estoniae

    2008-01-01

    Ansambel Fix peab 13. detsembril Tallinnas Saku Suurhallis oma 40. sünnipäeva. Kontserdi erikülaline on ansambel Apelsin, kaastegevad Jassi Zahharov ja HaleBopp Singers. Õhtut juhib Tarmo Leinatamm

  12. Fix 40!

    Index Scriptorium Estoniae

    2008-01-01

    Ansambel Fix peab 13. detsembril Tallinnas Saku Suurhallis oma 40. sünnipäeva. Kontserdi erikülaline on ansambel Apelsin, kaastegevad Jassi Zahharov ja HaleBopp Singers. Õhtut juhib Tarmo Leinatamm

  13. Comparative efficacy of indacaterol 150 µg and 300 µg versus fixed-dose combinations of formoterol + budesonide or salmeterol + fluticasone for the treatment of chronic obstructive pulmonary disease – a network meta-analysis

    OpenAIRE

    Cope, Shannon; Capkun-Niggli,Gorana; Gale,Rupert; Jardim, Jose; Jansen, Jeroen

    2011-01-01

    Shannon Cope1, Gorana Capkun-Niggli2, Rupert Gale3, José R Jardim4, Jeroen P Jansen11Mapi Values, Boston, MA, USA; 2Health Economics and Outcomes Research, Novartis Pharma AG, Basel, Switzerland; 3Novartis Horsham Research Centre, Horsham, UK; 4Respiratory Division, Federal University of São Paulo, BrazilObjective: To compare efficacy of indacaterol to that of fixed-dose combination (FDC) formoterol and budesonide (FOR/BUD) and FDC salmeterol and fluticasone (SAL/FP) for...

  14. Comparative efficacy of indacaterol 150 μg and 300 μg versus fixed-dose combinations of formoterol + budesonide or salmeterol + fluticasone for the treatment of chronic obstructive pulmonary disease – a network meta-analysis

    OpenAIRE

    Cope, Shannon; Capkun-Niggli,Gorana; Gale,Rupert; Jardim, José R; Jansen, Jeroen P

    2011-01-01

    Objective: To compare efficacy of indacaterol to that of fixed-dose combination (FDC) formoterol and budesonide (FOR/BUD) and FDC salmeterol and fluticasone (SAL/FP) for the treatment of chronic obstructive pulmonary disease (COPD) based on the available randomized clinical trials (RCTs). Methods: Fifteen placebo-controlled RCTs were included that evaluated: indacaterol 150 μg (n = 5 studies), indacaterol 300 μg (n = 4), FOR/BUD 9/160 μg (n = 2), FOR/BUD 9/320 μg (n = 3), SAL/FP 50/500 μg (n ...

  15. Pharmacodynamic effects of a new fixed-dose clopidogrel-aspirin combination compared with separate administration of clopidogrel and aspirin in patients treated with coronary stents: The ACCEL-COMBO trial.

    Science.gov (United States)

    Koh, Jin-Sin; Park, Yongwhi; Tantry, Udaya S; Ahn, Jong-Hwa; Kang, Min Gyu; Kim, Kyehwan; Jang, Jeong Yoon; Park, Hyun Woong; Park, Jeong Rang; Hwang, Seok-Jae; Kwak, Choong Hwan; Hwang, Jin-Yong; Gurbel, Paul A; Jeong, Young-Hoon

    2017-03-01

    Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin is a widely prescribed regimen to prevent ischemic events in patients undergoing percutaneous coronary intervention (PCI). A fixed-dose combination (FDC) capsule (HCP0911) has been developed to provide dosing convenience and improve adherence. We compared the antiplatelet effects of single daily dose HCP0911 with separate treatment with daily 75 mg clopidogrel plus 100 mg aspirin. This was a randomized, open-label, two-period, crossover, non-inferiority study conducted in stented patients who had been treated for at least 6 months with clopidogrel and aspirin. Thirty patients were randomly assigned to receive either daily 75 mg clopidogrel plus 100 mg aspirin treatment or HCP0911 for 2 weeks and then were crossed over to the other treatment for 2 weeks. Pharmacodynamic effects were measured with VerifyNow, light transmittance aggregometry (LTA), and thromboelastography (TEG(®)). The primary endpoint was P2Y12 Reaction Units (PRU) measured by VerifyNow. PRUs during treatment with HCP0911 were not inferior to those during separate treatment (202 ± 52 vs. 207 ± 60 PRU; mean difference, -5 PRU; 90% confidence interval of difference, -23 to 13 PRU; P for non-inferiority = 0.015 for predetermined limit). "BASE" and Aspirin Reaction Units by VerifyNow did not differ between the two treatments. During each treatment, there were no differences in maximal and final platelet aggregations by LTA (all P values ≥0.822) and TEG(®) measurements. In conclusion, in stented patients, the antiplatelet effect of a fixed-dose clopidogrel-aspirin combination, HCP0911, was not inferior to separate administration of clopidogrel and aspirin.

  16. 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.

  17. Development and Validation of Stability-Indicating RP-UPLC Method for Simultaneous Determination of Related Substances of S(−Amlodipine and S(−Metoprolol Succinate in Fixed Dose Combination Tablet Dosage Form

    Directory of Open Access Journals (Sweden)

    Suresh Shitole

    2014-01-01

    Full Text Available A novel, rapid, accurate, sensitive, precise, and stability-indicating reverse-phase ultra-performance liquid chromatographic (RP-UPLC method was developed and validated for determination of related substances of S(−Amlodipine and S(−Metoprolol Succinate in fixed dose combination tablet dosage form. The chromatographic separation was achieved with the use of Acquity UPLC HSS T3, 1.8 μm, 2.1 × 100 mm analytical column at 45°C employing a gradient elution. Mobile phase consisting of mobile phase-A (solution containing 5.0 gm of sodium dihydrogen phosphate monohydrate per liter of water and Acetonitrile in the ratio of 95 : 5 and mobile phase-B (Acetonitrile was used at a flow rate of 0.5 mL min−1 with injection volume of 10 μL and the detection was done at 232 nm using UV detector. The retention times of S(−Metoprolol Succinate and S(−Amlodipine were found to be 2.8 minutes and 8.1 minutes, respectively. During method validation all the parameters were evaluated as per ICH guidelines, which remained well within acceptable limits. This method can be used for the estimation of related substances of S(−Amlodipine and S(−Metoprolol Succinate in fixed dose combination tablet dosage form.

  18. Bioequivalence study between a fixed-dose single-pill formulation of nebivolol plus hydrochlorothiazide and separate formulations in healthy subjects using high-performance liquid chromatography coupled to tandem mass spectrometry.

    Science.gov (United States)

    Vespasiano, Celso Francisco Pimentel; Laurito, Tiago Luders; Iwamoto, Renan Donomae; Moreno, Ronilson Agnaldo; Mendes, Gustavo D; De Nucci, Gilberto

    2016-11-03

    Systemic arterial hypertension is a major risk factor for cerebrovascular disease. Therefore, adequate control of blood pressure is of enormous importance. One of the many fixed-dose single-pill antihypertensive formulations available on the market is the combination of nebivolol and hydrochlorothiazide. The objective of this study was to develop two distinct high-performance liquid chromatography coupled to tandem mass spectrometry methods to simultaneously quantify nebivolol and hydrochlorothiazide in human plasma. The methods were employed in a bioequivalence study, the first assay involving a nebivolol fixed-dose single-pill formulation based on healthy Brazilian volunteers. Nebilet HCT™ (nebivolol 5 mg + hydrochlorothiazide 12.5 mg tablet, manufactured by Menarini) was the test formulation. The reference formulations were Nebilet™ (nebivolol 5 mg tablet, manufactured by Menarini) and Clorana™ (hydrochlorothiazide 25 mg tablet, manufactured by Sanofi). For both analytes, liquid-liquid extraction was employed for sample preparation and the chromatographic run time was 3.5 min. The limits of quantification validated were 0.02 ng/mL for nebivolol and 1 ng/mL for hydrochlorothiazide. Since the 90% CI for Cmax , AUC(0-last) and AUC(0-inf) individual test/reference ratios were within the 80-125% interval indicative of bioequivalence, it was concluded that Nebilet HCT™ is bioequivalent to Nebilet™ and Clorana™.

  19. Cancer patients requiring interruption of long-term warfarin because of surgery or chemotherapy induced thrombocytopenia: the use of fixed sub-therapeutic doses of low-molecular weight heparin.

    Science.gov (United States)

    Saccullo, Giorgia; Malato, Alessandra; Raso, Simona; Santoro, Marco; Zammit, Valentina; Casuccio, Alessandra; Siragusa, Sergio

    2012-04-01

    No data are available regarding the management of cancer patients requiring interruption of long-term vitamin-K antagonist (VKA) therapy. For this purpose, we tested the efficacy and safety of fixed doses of low-molecular weight heparin (LMWH) in substitution of VKA because of invasive procedures or chemotherapy-induced thrombocytopenia. In cancer patients on VKA, therapy was discontinued 5 ± 1 days before surgery or chemotherapy. Heparin was given at prophylactic dosage in patients at low risk and at fixed subtherapeutic doses (3,800 or 4,000 UI anti-FXa, b.i.d.) in those at high-risk for thrombosis. LMWH was reinitiated 12 hr after surgery and VKA the day after. In patients receiving chemotherapy, LMWH was reinitiated 12/24 hr after obtaining a stable platelet count ≥ 30,000 mmc(3) and VKA after a stable platelet count ≥ 50,000 mmc(3) . Thromboembolism and major bleeding events were recorded from the time of VKA suspension to 30 ± 2 days postprocedure or until the next chemotherapy. Overall, 156 patients (56.4% at low risk and 43.5% at high risk for thrombosis) were enrolled; 34.6% underwent major surgery, 40.4% nonmajor surgery, and 25% chemotherapy. Thrombotic events occurred in five patients [3.2%, 95% confidence interval (CI): 1.41-7.27], four belonging to the high-risk and one to the low-risk group. Major bleeding occurred in five patients (3.2%, 95 CI: 1.41-7.27), all belonging to the high-risk group (three during major surgery and two during chemotherapy). In conclusion, LMWH given at fixed subtherapeutic is a feasible and relatively safe approach for bridging therapy in cancer patients on long-term VKA.

  20. Weight-Based Victimization toward Overweight Adolescents: Observations and Reactions of Peers

    Science.gov (United States)

    Puhl, Rebecca M.; Luedicke, Joerg; Heuer, Cheslea

    2011-01-01

    Background: Weight-based victimization has become increasingly reported among overweight youth, but little is known about adolescents' perceptions and observations of weight-based teasing and bullying. This study examined adolescents' observations of and reactions to weight-based victimization toward overweight students at school. Methods:…

  1. Weight-Based Victimization toward Overweight Adolescents: Observations and Reactions of Peers

    Science.gov (United States)

    Puhl, Rebecca M.; Luedicke, Joerg; Heuer, Cheslea

    2011-01-01

    Background: Weight-based victimization has become increasingly reported among overweight youth, but little is known about adolescents' perceptions and observations of weight-based teasing and bullying. This study examined adolescents' observations of and reactions to weight-based victimization toward overweight students at school. Methods:…

  2. Magnetic resonance imaging left ventricular mass reduction with fixed-dose angiotensin-converting enzyme inhibitor-based regimens in patients with high-risk hypertension.

    Science.gov (United States)

    Reichek, Nathaniel; Devereux, Richard B; Rocha, Ricardo A; Hilkert, Robert; Hall, Donna; Purkayastha, Das; Pitt, Bertram

    2009-10-01

    Left ventricular hypertrophy, a major cardiovascular risk factor for morbidity and mortality, is commonly caused by arterial hypertension. The renin-angiotensin-aldosterone system may contribute to the pathogenesis of left ventricular hypertrophy. The Assessment of Lotrel in Left Ventricular Hypertrophy and Hypertension Study compared a single-pill combination of amlodipine/benazepril at doses 5.0/20.0 mg, 5.0/40.0 mg, and 10.0/40.0 mg with hydrochlorothiazide/benazepril at doses 12.5/20.0 mg, 12.5/40.0 mg, and 25.0/40.0 mg on the reduction of left ventricular mass index measured by cardiac MRI in stage 2 hypertensive patients over 52 weeks of treatment in a randomized clinical trial. A total of 125 male and female patients, > or =55 years of age, with echocardiographic left ventricular hypertrophy and high-risk hypertension defined as blood pressure > or =160/100 mm Hg or current antihypertensive treatment were enrolled. After 52 weeks of treatment, left ventricular mass index was significantly reduced from baseline with amlodipine/benazepril (mean: 10.16 g/m(2)) or hydrochlorothiazide/benazepril (mean: 6.74 g/m(2); both Pamlodipine/benazepril (P=0.02). Both treatments were well tolerated.

  3. A randomized phase II trial of concurrent chemoradiation with two doses of radiotherapy, 60Gy and 66Gy, concomitant with a fixed dose of oral vinorelbine in locally advanced NSCLC

    DEFF Research Database (Denmark)

    Hansen, Olfred; Knap, Marianne; Khalil, Azza Ahmed

    2017-01-01

    Introduction: In order to test the best performing radiation dose with a convenient chemotherapy schedule of an oral formulation of radio-sensitizing vinorelbine in inoperable locally advanced non-small cell lung cancer (NSCLC), we performed a randomized phase II trial based on a "pick the winner...

  4. A Randomized Trial of Fixed-Dose Combination Brinzolamide 1%/Brimonidine 0.2% as Adjunctive Therapy to Travoprost 0.004.

    Science.gov (United States)

    Feldman, Robert M; Katz, Gregory; McMenemy, Matthew; Hubatsch, Douglas A; Realini, Tony

    2016-05-01

    To evaluate the safety and efficacy of adding fixed-combination brinzolamide 1%/brimonidine 0.2% (BBFC) as adjunctive therapy to travoprost 0.004% (TRAV) in patients with open-angle glaucoma or ocular hypertension. Multicenter, randomized, double-masked, parallel-group phase 4 clinical trial. setting: Multicenter; 32 sites in the United States. Total of 233 patients with open-angle glaucoma or ocular hypertension and with mean intraocular pressure (IOP) ≥21 mm Hg and TRAV monotherapy. Masked BBFC or vehicle (3 times daily) adjunctive to TRAV for 6 weeks. Mean diurnal IOP averaged over 8 AM, 10 AM, 3 PM, and 5 PM time points at week 6. Superiority of BBFC+TRAV over vehicle+TRAV was based on statistical significance of a treatment difference favoring BBFC+TRAV. Mean diurnal IOP at week 6 (least squares mean ± standard error) was 17.6 ± 0.4 mm Hg and 20.7 ± 0.4 mm Hg in the BBFC+TRAV and vehicle+TRAV groups, respectively (between-group difference, -3.2 ± 0.5 mm Hg; P TRAV over vehicle+TRAV was established. Mean and percent diurnal IOP change from baseline were significantly greater with BBFC+TRAV compared with vehicle+TRAV (P TRAV, 12.8%; vehicle+TRAV, 6.0%). Adjunctive treatment with BBFC added to TRAV resulted in lower mean diurnal IOP after 6 weeks of treatment compared with vehicle added to TRAV; this difference was both statistically and clinically significant. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Hybrid Weighted-based Clustering Routing Protocol for Railway Communications

    Directory of Open Access Journals (Sweden)

    Jianli Xie

    2013-12-01

    Full Text Available In the paper, a hybrid clustering routing strategy is proposed for railway emergency ad hoc network, when GSM-R base stations are destroyed or some terminals (or nodes are far from the signal coverage. In this case, the cluster-head (CH election procedure is invoked on-demand, which takes into consideration the degree difference from the ideal degree, relative clustering stability, the sum of distance between the node and it’s one-hop neighbors, consumed power, node type and node mobility. For the clustering forming, the weights for the CH election parameters are allocated rationally by rough set theory. The hybrid weighted-based clustering routing (HWBCR strategy is designed for railway emergency communication scene, which aims to get a good trade-off between the computation costs and performances. The simulation platform is constructed to evaluate the performance of our strategy in terms of the average end-to-end delay, packet loss ratio, routing overhead and average throughput. The results, by comparing with the railway communication QoS index, reveal that our strategy is suitable for transmitting dispatching voice and data between train and ground, when the train speed is less than 220km/h

  6. Long-term use of fluticasone propionate/salmeterol fixed-dose combination and incidence of cataracts and glaucoma among chronic obstructive pulmonary disease patients in the UK General Practice Research Database

    Directory of Open Access Journals (Sweden)

    Miller DP

    2011-09-01

    Full Text Available David P Miller, Stephanie E Watkins, Tim Sampson, Kourtney J Davis WorldWide Epidemiology, GlaxoSmithKline, Durham, NC, USA Objectives: Some large population-based studies have reported a dose-related increased risk of cataracts and glaucoma associated with use of inhaled corticosteroids (ICS in patients with asthma or chronic obstructive pulmonary disease (COPD. We evaluated the association between use of ICS-containing products, specifically fluticasone propionate/salmeterol fixed-dose combination (FSC, and incidence of cataracts and glaucoma among patients with COPD in a large electronic medical record database in the United Kingdom. Methods: We identified a cohort of patients aged 45 years and over with COPD in the General Practice Research Database (GPRD between 2003 and 2006. Cases of incident cataracts or glaucoma were defined based on diagnosis and procedure codes and matched to controls from the risk set to estimate odds ratios (OR and 95% confidence intervals (CI. The association with FSC or ICS exposure was modeled using conditional logistic regression. Medication exposure was assessed with respect to recency, duration, and number of prescriptions prior to the index date. Average daily dose was defined as none, low (1–250 mcg, medium (251–500 mcg, high (501–1000 mcg, or very high (1001+ mcg using fluticasone propionate (FP equivalents. Results: We identified 2941 incident cataract cases and 327 incident glaucoma cases in the COPD cohort (n = 53,191. FSC or ICS prescriptions were not associated with risk of incident cataracts or glaucoma for any exposure category, after adjusting for confounders. We observed a lack of a dose response in all analyses, where low dose was the reference group. The odds of cataracts associated with FSC dose were medium OR: 1.1 (95% CI: 0.9–1.4; high OR: 1.2 (95% CI: 0.9–1.5; and very high OR: 1.2 (95% CI: 0.9–1.7. The odds of glaucoma associated with FSC dose: medium OR: 1.0 (95% CI: 0.5–2

  7. Stavudine- and nevirapine-related drug toxicity while on generic fixed-dose antiretroviral treatment: incidence, timing and risk factors in a three-year cohort in Kigali, Rwanda.

    Science.gov (United States)

    van Griensven, Johan; Zachariah, Rony; Rasschaert, Freya; Mugabo, Jules; Atté, Edi F; Reid, Tony

    2010-02-01

    This cohort study was conducted to report on the incidence, timing and risk factors for stavudine (d4T)- and nevirapine (NVP)-related severe drug toxicity (requiring substitution) with a generic fixed-dose combination under program conditions in Kigali, Rwanda. Probability of 'time to first toxicity-related drug substitution' was estimated using the Kaplan-Meier method and Cox-proportional hazards modeling was used to identify risk factors. Out of 2190 adults (median follow-up: 1.5 years), d4T was replaced in 175 patients (8.0%) for neuropathy, 69 (3.1%) for lactic acidosis and 157 (7.2%) for lipoatrophy, which was the most frequent toxicity by 3 years of antiretroviral treatment (ART). NVP was substituted in 4.9 and 1.3% of patients for skin rash and hepatotoxicity, respectively. Use of d4T 40 mg was associated with increased risk of lipoatrophy and early (strategies.

  8. The efficacy and safety of fixed-dose combination of amlodipine/benazepril in Chinese essential hypertensive patients not adequately controlled with benazepril monotherapy: a multicenter, randomized, double-blind, double-dummy, parallel-group clinical trial.

    Science.gov (United States)

    Yan, Pingping; Fan, Weihu

    2014-01-01

    This double-blind, double-dummy clinical trial evaluated the efficacy and safety of two strengths of fixed-dose combination of amlodipine/benazepril in Chinese hypertensive patients not adequately controlled with benazepril. Of 442 patients who received treatment with benazepril 10 mg for 4 weeks, 341 patients failed to achieve to diastolic blood pressure (DBP) amlodipine/benazepril 2.5/10 mg, or amlodipine/benazepril 5/10 mg, or benazepril 10 mg for 8 weeks. BP reductions with amodipinel/benazepril 2.5/10 mg (15.2/11.8 mmHg) or amlodipine/benazepril 5/10 mg (15.4/12.4 mmHg) were significantly greater than that with benazepril 10 mg (9.88/9.46 mmHg) at study end (p benazepril). BP control rate was 83.8% with amlodipine/benazepril 2.5/10 mg, 80.2% with amlodipine/benazepril 5/10 mg, 64.9% with benazepril 10 mg at study end (p benazepril). Three groups were generally well tolerated. Our study indicated that amlodipine/benazepril fixed-dose combination offered significant additional BP reductions and BP control rate compared with the continuation of benazepril monotherapy. No significant differences were observed in both BP reductions and BP control rate between amlodipine/benazepril 2.5/10 mg and amlodipine/benazepril 5/10 mg.

  9. Tramadol hydrochloride 75 mg/dexketoprofen 25 mg oral fixed-dose combination in moderate-to-severe acute pain: sustained analgesic effect over a 56-h period in the postoperative setting.

    Science.gov (United States)

    Montero Matamala, A; Bertolotti, M; Contini, M P; Guerrero Bayón, C; Nizzardo, A; Paredes Lario, I; Pizà Vallespir, B; Scartoni, S; Tonini, G; Capriati, A; Pellacani, A

    2017-06-01

    Multimodal analgesia constitutes a common strategy in pain management. A tramadol hydrochloride 75 mg/dexketoprofen 25 mg oral fixed combination (TRAM/DKP 75 mg/25 mg) has been recently registered and released in Europe for the treatment of moderate-to-severe acute pain. This paper provides additional analyses on the results of two phase III clinical trials (DEX-TRA-04 and DEX-TRA-05) on postoperative pain to document its sustained effect. The analysis was applied to a modified intention-to-treat population (mITT, n = 933) of patients undergoing active treatment from the first dose, to assess the sustained effect of TRAM/DKP 75 mg/25 mg on pain intensity (PI-VAS 0-100) over 56 h from first drug intake. The superior analgesic effect of TRAM/DKP 75 mg/25 mg over 56 h in terms of difference in PI-VAS (mean [SE]) was shown for DEX-TRA-04 (-11.0 [0.55] over dexketoprofen 25 mg and -9.1 [0.55] over tramadol 100 mg, P ≤ 0.0001) and for DEX-TRA-05 (-10.4 [0.51] over dexketoprofen 25 mg and -8.3 [0.51] over tramadol 100 mg, P ≤ 0.0001). The statistical analysis performed on data coming from both studies confirms the superior sustained analgesia of TRAM/DKP 75 mg/25 mg over tramadol 100 mg and dexketoprofen 25 mg. These results are consistent with the previously published data obtained on the ITT population and strongly support the role of this oral fixed-dose combination in the treatment of moderate-to-severe acute pain. Copyright 2017 Clarivate Analytics.

  10. Absence of a significant pharmacokinetic interaction between atorvastatin and fenofibrate: A randomized, crossover, study of a fixed-dose formulation in healthy Mexican subjects

    Directory of Open Access Journals (Sweden)

    Omar ePatiño-Rodríguez

    2015-01-01

    Full Text Available Several clinical trials have substantiated the efficacy of the co-administration of statins like atorvastatin and fibrates. Without information currently available about the interaction between the two drugs, a pharmacokinetic study was conducted to investigate the effect when both drugs were co-administered. The purpose of this study was to investigate the pharmacokinetic profile of tablets containing atorvastatin 20 mg, or the combination of atorvastatin 20 mg with fenofibrate 160 mg administered to healthy Mexican volunteers. This was a randomized, two-period, two-sequence, crossover study; 36 eligible subjects aged between 20 to 50 years were included. Blood samples were collected up to 96 h after dosing, and pharmacokinetic parameters were obtained by non-compartmental analysis. Adverse events were evaluated based on subject interviews and physical examinations. Area under the concentration-time curve (AUC and maximum plasma drug concentration (Cmax were measured for atorvastatin as the reference and atorvastatin and fenofibrate as the test product for bioequivalence design. The estimation computed (90% confidence intervals for atorvastatin and fenofibrate combination versus atorvastatin for Cmax, AUC0-t and AUC0-∞, were 102,09, 125,95 and 120,97% respectively. These results suggest that atorvastatin and fenofibrate have no relevant clinical-pharmacokinetic drug interaction.

  11. A weight based genetic algorithm for selecting views

    Science.gov (United States)

    Talebian, Seyed H.; Kareem, Sameem A.

    2013-03-01

    Data warehouse is a technology designed for supporting decision making. Data warehouse is made by extracting large amount of data from different operational systems; transforming it to a consistent form and loading it to the central repository. The type of queries in data warehouse environment differs from those in operational systems. In contrast to operational systems, the analytical queries that are issued in data warehouses involve summarization of large volume of data and therefore in normal circumstance take a long time to be answered. On the other hand, the result of these queries must be answered in a short time to enable managers to make decisions as short time as possible. As a result, an essential need in this environment is in improving the performances of queries. One of the most popular methods to do this task is utilizing pre-computed result of queries. In this method, whenever a new query is submitted by the user instead of calculating the query on the fly through a large underlying database, the pre-computed result or views are used to answer the queries. Although, the ideal option would be pre-computing and saving all possible views, but, in practice due to disk space constraint and overhead due to view updates it is not considered as a feasible choice. Therefore, we need to select a subset of possible views to save on disk. The problem of selecting the right subset of views is considered as an important challenge in data warehousing. In this paper we suggest a Weighted Based Genetic Algorithm (WBGA) for solving the view selection problem with two objectives.

  12. Pharmacokinetics of metformin hydrochloride and glipizide in fixed-dose combination in healthy Chinese volunteers%盐酸二甲双胍格列吡嗪胶囊的健康人体药动学研究

    Institute of Scientific and Technical Information of China (English)

    马智宇; 曲斌; 丁娅; 宋敏; 杭太俊

    2012-01-01

    Objective: To investigate the clinical plasma pharmacokinetics of metformin hydrochloride ( MET) and glipizide(GLP) in healthy Chinese volunteers post oral administration of fixed -dose combination capsules, each contains 250 mg metformin hydrochloride and 2. 5 mg glipizide. Methods;20 healthy Chinese volunteers were randomly divided into two groups. Group I was administrated with two incremental oral fixed -dose combination capsules(250 mg MET/2. 5 mg GLP, 750 mg MET/7. 5 mg GLP), respectively. Glipizide tablets(5 mg) , metformin hydrochloride capsules(500 mg), and fixed -doses combination capsules(500 mg MET/5 mg GLP) , were given to Group H with three - period, crossover study design, and multiple oral fix - doses combination capsules were also given to thisgroup. HPLC - UV was used for the determination of metformin and LC - MS/MS for glipizide. The main pharmaco-kinetic parameters and the statistic analysis results were evaluated by DAS 2.0 software. Results: After single oral dose of three incremental fixed -dose combination capsules (250 mg MET/2.5 mg GLP, 500 mg MET/5 mg GLP, 750 mg MET/7.5 mg GLP) and multiply oral doses of the fixed -dose combination capsules(500 mg MET/5 mg GLP), the main pharmacokinetic parameters of metformin hydrochloride were as follows; Cmax were (718 ± 122), (1179 ±308), (1494 ±174) and (979 ±268) ng·mL-1; Tmax were (1.7 ±0.63), (3.4 ±0.94), (2.4 ±0.70) and (3.9 ±1.4) h; AUC0_t, were (4519 ±606), (8646 ±2757), (10040 ±1501) and (8965 ±2200) ng · h · mL-1; t1/2 were (3.46 ±0. 34), (4.74 ±0. 80), (4.90 ± 1.42) and (4.99 ±0. 58) h, respectively. The main pharmacokinetic parameters of glipizide were as follows; Cmax were (294 ±63.4), (432 ±98.7), (641 ±76. 5) and (273 ±51.5) ng · mL-1; Tmax were (1.8 ±0.54), (1.9±0.78), (1.9±0.47) and (4.0±2.0) h; AUC0_t were (1642 ±340), (2788 ±994), (3508 ±758) and (2841 ± 1003) ng · h · mL-1; t1/2 were (4.04 ±0.53), (4.70 ±0.75), (3. 88 ±0. 77) and (6.46 ±5. 83

  13. The effect of type of vaginal insert and dose of pLH on embryo production, following fixed-time AI in a progestin-based superstimulatory protocol in Nelore cattle.

    Science.gov (United States)

    Nogueira, Marcelo F Gouveia; Fragnito, Paulo S; Trinca, Luzia A; Barros, Ciro M

    2007-02-01

    The objective was to analyze and report field data focusing on the effect of type of progesterone-releasing vaginal insert and dose of pLH on embryo production, following a superstimulatory protocol involving fixed-time artificial insemination (FTAI) in Nelore cattle (Bos taurus indicus). Donor heifers and cows (n = 68; 136 superstimulations over 2 years) received an intravaginal, progesterone-releasing insert (CIDR or DIB, with 1.9 or 1.0 g progesterone, respectively) and 3-4 mg of estradiol benzoate (EB) i.m. at random stages of the estrous cycle. Five days later (designated Day 0), cattle were superstimulated with a total of 120-200 mg of pFSH (Folltropin-V), given twice daily in decreasing doses from Days 0 to 3. All cattle received two luteolytic doses of PGF2alpha at 08:00 and 20:00 h on Day 2 and progesterone inserts were removed at 20:00 h on Day 3 (36 h after the first PGF2alpha injection). Ovulation was induced with pLH (Lutropin-V, 12.5 or 25 mg, i.m.) at 08:00 h on Day 4 with FTAI 12, 24 and in several cases, 36 h later. Embryos were recovered on Days 11 or 12, graded and transferred to synchronous recipients. Overall, the mean (+/-S.E.M.) number of total ova/embryos (13.3 +/- 0.8) and viable embryos (9.4 +/- 0.6) and pregnancy rate (43.5%; 528/1213) did not differ among groups, but embryo viability rate (overall, 70.8%) was higher in donors with a DIB (72.3%) than a CIDR (68.3%, P = 0.007). In conclusion, the administration of pLH 12 h after progesterone removal in a progestin-based superstimulatory protocol facilitated fixed-time AI in Nelore donors, with embryo production, embryo viability and pregnancy rates after embryo transfer, comparable to published results where estrus detection and AI was done. Results suggested a possible alternative, which would eliminate the need for estrus detection in donors.

  14. Evaluación de la toxicidad aguda por el procedimiento de dosis fijas de un extracto de Boldoa purpurascens Cav. (Evaluation of the acute toxicity of the method fixed dose procedure of an extract of Boldoa prurpurascens Cav.

    Directory of Open Access Journals (Sweden)

    Pérez Machín, Maykel

    2008-03-01

    Full Text Available ResumenSe realizó un estudio experimental con el objetivo de evaluar el posible efecto tóxico de un extracto acuoso liofilizado de Boldoa purpurascen Cav. (nitro blanco. Para el desarrollo del mismo se utilizó el Procedimiento de Dosis Fijas (FDP, utilizando una dosis límite de 2000 mg/kg de peso corporal. Los animales seleccionados fueron ratas de la línea Sprague Dawley, con un peso comprendido entre 150 y 200 g. Los resultados demostraron la inocuidad de la planta al no observarse signos ni síntomas de toxicidad. El peso corporal se comportó acorde a la curva de crecimiento de la especie y no se apreciaron alteraciones macroscópicas en los órganos estudiados, todo lo que permite afirmar que la DL50 se ubica por encima de 2000 mg/kg PC, considerándose el producto como No Clasificado (no tóxico. SummaryAn experimental study to assess the toxic effects of an aqueous and later lyophilised extract of Boldoa purpurascens Cav. (nitro blanco was carried out. It was employed the alternative Fixed Dose Procedure. There were used Sprague Dawley rats weighing between 150 and 200 g, which received a limit dose of 2000 mg/kg body weight and were kept under standardized experimental conditions. Results showed neither signs nor symptoms of toxicity. Bodyweight behaved consistent with the growing curve of this species and there were no alterations in macroscopic observations on main organs. The LD50 of this extract is located above 2000 mg/kg body weight, considering it as Non Classified (non toxic.

  15. Combating Weight-Based Bullying in Schools: Is There Public Support for the Use of Litigation?

    Science.gov (United States)

    Puhl, Rebecca; Luedicke, Joerg; King, Kelly M.

    2015-01-01

    Background: Bullying litigation is an emerging area of law that has increased in response to serious cases of bullying at school. Weight-based bullying is prevalent at school, but no research has examined the use of litigation to address this problem. We assessed public support for litigation approaches to address weight-based bullying at school,…

  16. The evolution of systolic blood pressure as a strong predictor of cardiovascular risk and the effectiveness of fixed-dose ARB/CCB combinations in lowering levels of this preferential target

    Directory of Open Access Journals (Sweden)

    Jean-Jacques Mourad

    2008-12-01

    Full Text Available Jean-Jacques MouradHypertension Unit, Avicenne Hospital – AP-HP and Paris XIII University Bobigny, FranceAbstract: Elevated blood pressure is an important cardiovascular risk factor. Although targets for both diastolic blood pressure (DBP and systolic blood pressure (SBP are defined by current guidelines, DBP has historically taken precedence in hypertension management. However, there is strong evidence that SBP is superior to DBP as a predictor of cardiovascular events. Moreover, achieving control of SBP is assuming greater importance amongst an aging population. In spite of the growing recognition of the importance of SBP in reducing cardiovascular risk and the emphasis by current guidelines on SBP control, a substantial proportion of patients still fail to achieve SBP targets, and SBP control is achieved much less frequently than DBP control. Thus, new approaches to the management of hypertension are required in order to control SBP and minimize cardiovascular risk. Fixed-dose combination (FDC therapy is an approach that offers the advantages of multiple drug administration and a reduction in regimen complexity that favors compliance. We have reviewed the latest evidence demonstrating the efficacy in targeting SBP of the most recent FDC products; combinations of the calcium channel blocker (CCB, amlodipine, with angiotensin receptor blockers (ARBs, valsartan or olmesartan. In addition, results from studies with new classes of agent are outlined.Keywords: hypertension, systolic blood pressure, angiotensin receptor blocker, calcium channel blocker, combination therapy

  17. Population pharmacokinetic modeling and noncompartmental analysis demonstrated bioequivalence between metformin component of metformin/vildagliptin fixed-dose combination products and metformin immediate-release tablet sourced from various countries.

    Science.gov (United States)

    Chitnis, Shripad D; Han, Yi; Yamaguchi, Masayuki; Mita, Sachiko; Zhao, Rong; Sunkara, Gangadhar; Kulmatycki, Kenneth

    2016-01-01

    Metformin is the first-line pharmacotherapy choice for treating type-2 diabetes mellitus, alone or in combination with other antidiabetic drugs. During the development of immediate-release (IR) metformin containing novel fixed-dose combination (FDC) products, several health-authorities require sponsors to demonstrate bioequivalence between FDC products and the country-sourced metformin for market approval. Eight bioequivalence studies that compared metformin/vildagliptin FDC product (test) to metformin IR tablet sourced from various countries (reference) were conducted. A population pharmacokinetic (PPK) analysis of pooled metformin concentration-time data was performed to evaluate whether country-sourced metformin is a significant covariate. The PPK analysis demonstrated that there was no clinically relevant effect of metformin source or race/ethnicity on metformin pharmacokinetics. Also, noncompartmental analysis conducted showed that 90%CI of geometric mean ratios of test to reference metformin formulations, calculated for maximum-concentration and exposure parameters, were within the 80%-125% criteria, indicating comparable metformin exposure regardless of the country-sourced metformin IR formulation. These results are consistent with the biopharmaceutics properties of metformin and provide scientific evidence that after assessing in vitro dissolution of novel FDC formulation, additional bioequivalence studies with multiple countries' reference products may not be required once bioequivalence is established with 1 country-sourced IR metformin formulation.

  18. 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

    2012-02-01

    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.

  19. Pregnancy rates after fixed-time artificial insemination of Brahman heifers treated to synchronize ovulation with low-dose intravaginal progesterone releasing devices, with or without eCG.

    Science.gov (United States)

    Butler, S A A; Atkinson, P C; Boe-Hansen, G B; Burns, B M; Dawson, K; Bo, G A; McGowan, M R

    2011-11-01

    The objective was to determine whether eCG in an ovulation synchronization protocol with an intravaginal progesterone (P(4))-releasing device (IPRD) containing a low dose of P(4) improves pregnancy rate (PR) to fixed-time AI (FTAI) in Bos indicus heifers. Day 0, 2 y old Brahman heifers were allocated to either eCG+ (n = 159) or eCG- (n = 157) treatment groups. All heifers were weighed, body condition scored (BCS), and ultrasonographically examined to measure uterine horn diameter and presence of a CL. On Day 0, all heifers received a low-dose IPRD (0.78 g P(4)) and 1 mg of estradiol benzoate (EB) im. On Day 8, the IPRD was removed, all heifers received 500 μg cloprostenol im, and those in the eCG+ treatment group received 300 IU of eCG im. On Day 9, all heifers received 1 mg EB im. All heifers were FTAI 52 to 56 h after IPRD removal. Ten days after FTAI, heifers were exposed to bulls. Heifers were diagnosed as pregnant to FTAI, natural mating, or not detectably pregnant (NDP) 65 d after FTAI. Treatment with eCG+ as compared to eCG- did not affect PR to FTAI (28.9 vs 30.6%; P = 0.590), natural mating (51.3 vs 47.7%; P = 0.595), or overall (65.4 vs 63.7%; P = 0.872). Mean live weight gain from Days 0 to 65 d post-FTAI was higher in heifers pregnant to FTAI (72.29 ± 4.26 kg; P = 0.033) and overall (66.83 ± 3.65 kg; P = 0.021), compared to heifers that were NDP (60.03 ± 3.16 kg). Uterine diameter group, 9-11, 12-13, and 14-20 mm (26.2, 31.3, and 33.3%; P = 0.256), presence and absence of CL (29.8 vs 29.4%; P = 0.975), AI technicians 1, 2, and 3 (32.6, 28.8, and 22.4%; P = 0.293) and sires A, B, and C (23.9, 36.0 and 27.0%; P = 0.122) had no effect on PR to FTAI, natural mating, or overall. In conclusion, treatment of primarily cycling Brahman heifers with 300 IU eCG in conjunction with a low P(4)-dose (0.78 g) IPRD and EB to synchronize ovulation, did not improve PR after FTAI, natural mating, or overall. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Efficacy and tolerability of a switch to fixed-dose combination therapy with amlodipine besylate/benazepril hydrochloride after monotherapy with amlodipine besylate: Data from the African-American subpopulation of a practice-based, open-label study (the LOGIC study)☆

    OpenAIRE

    Gatlin, Marjorie; Jarrett, Wentworth G.; Nwose, Oliseyenum M.; LOGIC (LOtrel: Gauging Improved Control) Study Investigators

    2004-01-01

    Background: The LOGIC (LOtrel: Gauging Improved Control) study assessed the efficacy and tolerability of switching from amlodipine besylate monotherapy to fixed-dose combination therapy with amlodipine besylate/benazepril hydrochloride (HCI) in patients who were experiencing uncontrolled blood pressure (BP) or edema with monotherapy.

  1. Progress on the treatment of pancreatic andenocarcinoma by fixed dose-rate infusion of gemcitabine%吉西他滨固定剂量率输注治疗胰腺癌的研究进展

    Institute of Scientific and Technical Information of China (English)

    邱满堂; 许青

    2012-01-01

    OBJECTIVE: This paper is aimed to review the progress on the treatment of pancreatic adenocarcinoma by gemcitabine administrated at fixed dose-rate (FDR) infusion and discuss the application of FDR gemcitabine (FDR-GEM). METHODS: Database'of PubMed, CNKI, Wanfang and Chinese Biomedical database were searched using key words "gemcitabine, fixed dose-rate, pancreatic adenocarcinoma" from 01,2000 to 12,2011. Publishing time and languages were not limited. Pharmacological researches, clinical trials, reviews and meta-analyses of FDR-GEM were collected. A number of 253 searching records were screened, and 26 eligible articles were included. The inclusion criteria were: 1) clinical trails or meta-analyses comparing FDR infusion and standard infusion of gemcitabine; 2) studies about the pharmacology of FDR infusion of gemcitabine. RESULTS: Pharmacological researches had demonstrated that the accumulation of gemcitabine triphosphate could reach maximum velocity with FDR-GEM. Tempero 's randomized controlled trial showed that FDR-GEM improved survival of patients with pancreatic adenocarcinoma but with more hematological toxicities compared to standard infusion. FDR-GEM also had satisfying survival when in combination with other agents in recent clinical trials and hematological toxicities were less frequently with a relatively low dose. CONCLUSION: FDR-GEM can improve patients' survival for patients of pancreatic adenocarcinoma but with higher incidence of hematological toxicities.%目的:总结国内外吉西他滨固定剂量率( FDR)输注治疗胰腺癌的研究进展,探讨其临床应用前景.方法:检索数据库PubMed、CNKI、万方及中国生物医学文献数据库2000-01-2011-12文献,以“吉西他滨、固定剂量率、胰腺癌”等为关键词,不限定发表时间和语言;纳入研究FDR吉西他滨的基础研究、临床试验、综述和meta分析,共检索到文献253篇.符合纳入标准的文献26篇.纳入标准:1):比较吉西他滨FDR

  2. Efficacy and safety of a fixed-dose combination of mometasone furoate and formoterol fumarate in subjects with moderate to very severe COPD: results from a 52-week Phase III trial

    Directory of Open Access Journals (Sweden)

    Tashkin DP

    2012-02-01

    Full Text Available Donald P Tashkin1, Dennis E Doherty2, Edward Kerwin3, Carlos E Matiz-Bueno4, Barbara Knorr5, Tulin Shekar5, Sibabrata Banerjee5, Heribert Staudinger51David Geffen School of Medicine at UCLA, Los Angeles, CA, 2Division of Pulmonary, Critical Care, and Sleep Medicine, University of Kentucky, Lexington, KY, 3Clinical Research Institute of Southern Oregon, Medford, OR USA; 4Fundación Salud Bosque, Bogota, Colombia; 5Merck Sharp & Dohme Corp, Whitehouse Station, NJ USABackground: A clinical trial of mometasone furoate/formoterol fumarate (MF/F administered via a metered-dose inhaler in subjects with moderate to very severe chronic obstructive pulmonary disease (COPD investigated the efficacy and safety of a fixed-dose combination of MF/F.Methods: This multicenter, double-blind, placebo-controlled trial had a 26-week treatment period and a 26-week safety extension. Subjects (n = 1055; ≥40 years were current or ex-smokers randomized to twice-daily treatment with inhaled MF/F 400/10 µg, MF/F 200/10 µg, MF 400 µg, F 10 µg, or placebo. The coprimary endpoints of the trial were mean changes from baseline in forced expiratory volume in 1 second (FEV1 over 0–12 hours (AUC0–12 FEV1 with MF/F versus MF, and in morning predose FEV1 with MF/F versus F. Key secondary endpoints were quality of life (Saint George’s Respiratory Questionnaire [SGRQ], symptom-free nights, and partly stable COPD at 26 weeks, as well as time to first COPD exacerbation.Results: Significant improvements in FEV1 AUC0–12 occurred at endpoint with MF/F 400/10 and MF/F 200/10 versus MF 400 (P ≤ 0.007. Significant bronchodilation occurred in 5 minutes with MF/F, and serial spirometry demonstrated sustained FEV1 improvements with MF/F over the treatment period. Significant improvements in morning predose FEV1 occurred with both MF/F doses, and these effects were further investigated by excluding results for subjects whose morning FEV1 data were collected >2 days after the last

  3. Efficacy and safety of fixed dose combination of arterolane maleate and piperaquine phosphate dispersible tablets in paediatric patients with acute uncomplicated Plasmodium falciparum malaria: a phase II, multicentric, open-label study.

    Science.gov (United States)

    Toure, Offianan Andre; Rulisa, Stephen; Anvikar, Anupkumar R; Rao, Ballamudi S; Mishra, Pitabas; Jalali, Rajinder K; Arora, Sudershan; Roy, Arjun; Saha, Nilanjan; Iyer, Sunil S; Sharma, Pradeep; Valecha, Neena

    2015-11-25

    The World Health Organization (WHO) recommends artemisinin combination therapy (ACT) for the treatment of uncomplicated Plasmodium falciparum malaria. The present study investigated the efficacy and safety of fixed dose combination (FDC) of arterolane maleate 37.5 mg and piperaquine phosphate (PQP) 187.5 mg dispersible tablets in paediatric patients aged 6 months to 12 years. Male and female patients aged 6 months to 12 years who were confirmed cases of P. falciparum mono-infection with fever or documented history of fever in the previous 24 h were included. The patients were administered FDC of arterolane maleate and PQP as single daily doses for three consecutive days based on their age. The primary efficacy outcome was proportion of patients with polymerase chain reaction (PCR)-corrected adequate clinical and parasitological response (ACPR) on day 28. Safety was analysed based on adverse events (AE), laboratory abnormalities and abnormalities on electrocardiograph. A total of 141 eligible paediatric patients received FDC of arterolane maleate and PQP in a 42-day follow-up study. All the enrolled patients (141) were included in intention to treat (ITT) and safety analyses, and 126 patients were considered in per protocol (PP) population. The PCR-corrected ACPR on day 28 was achieved in all patients (100 %; 95 % CI 97.11-100) included in PP population. The median parasite clearance time (PCT) and fever clearance time (FCT) were 24 h (95 % CI 18.0-24.0) and 10 h (95 % CI 4.0-18.0), respectively. The most frequently reported clinical AE was vomiting. Majority of the AEs were mild to moderate in severity and resolved without sequelae. No patient was discontinued for any QTc (corrected QT interval) prolongation. No deaths or serious AEs were reported during the study. The findings from this study showed that FDC of arterolane maleate and PQP effectively cures P. falciparum malaria and attains acceptable level of cure by day 28 in paediatric patients. The efficacy and

  4. Adherence to Treatment, Safety, Tolerance, and Effectiveness of Perindopril/Amlodipine Fixed-Dose Combination in Greek Patients with Hypertension and Stable Coronary Artery Disease: A Pan-Hellenic Prospective Observational Study of Daily Clinical Practice.

    Science.gov (United States)

    Liakos, Charalampos I; Papadopoulos, Dimitrios P; Kotsis, Vasilios T

    2017-05-02

    Initiation of antihypertensive therapy with a two-drug fixed-dose combination (FDC) in a single tablet may be recommended in patients at high risk of cardiovascular events to improve adherence and effectiveness. Preferred combinations include an angiotensin-converting enzyme inhibitor with a dihydropyridine calcium antagonist. This study assessed adherence to and the safety, tolerance, and effectiveness of the perindopril/amlodipine FDC in Greek patients with hypertension and stable coronary artery disease (CAD) over a 4-month period. A total of 1907 patients with hypertension and CAD (59.1% males) who had recently (≤2 weeks) commenced treatment with the perindopril/amlodipine FDC (5/5, 5/10, 10/5, or 10/10 mg) were studied at baseline and at 1 and 4 months. Adherence to treatment was assessed with the Morisky Medication-taking Adherence Scale (MMAS). Seven patients (0.4%) did not attend the scheduled visits. In total, 1607 (84.6%) patients received a constant treatment dose throughout the study. High adherence (MMAS score = 0) was reported by 1592 (83.6%), 1628 (85.7%), and 1477 (77.7%) patients at the second and the third visit and at both visits, respectively. Adverse reactions were reported by only 13 (0.7%) patients, were all minor, and did not result in treatment discontinuation. Office blood pressure (BP) was significantly decreased at the third visit (130.8 ± 8.4/78.2 ± 6.4 mmHg) compared with baseline (156.5 ± 15.0/89.9 ± 9.6 mmHg; p hypertension at baseline showed a reduction in BP of 19.3/9.4, 31.5/13.5, and 47.8/22.2 mmHg, respectively (p hypertension (≥140/90 mmHg) was notably reduced from 90.3% at baseline to 18.5% at the third visit. The perindopril/amlodipine FDC is characterized by high adherence and effectiveness, regardless of previous treatment. Degree of BP reduction was related to baseline BP levels. Clinical trials registration number (Protocol Number): IC4 - 05985 - 011 - GRC.

  5. Efficacy and Tolerability of Travoprost 0.004%/Timolol 0.5% Fixed-Dose Combination for the Treatment of Primary Open-Angle Glaucoma or Ocular Hypertension Inadequately Controlled with Beta-Blocker Monotherapy

    Science.gov (United States)

    Park, Ki Ho; Hubatsch, Douglas A.; Erichev, Valeriy; Paczka, Jose A.; Roberts, Timothy V.

    2017-01-01

    Objective. To evaluate the efficacy and tolerability of travoprost 0.004%/timolol 0.5% fixed-dose combination (TTFC) in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT) inadequately controlled on beta-blocker monotherapy. Methods. In this phase IV, open-label study, 156 patients on beta-blocker monotherapy with mean intraocular pressure (IOP) between 18 and 32 mmHg were randomized (no washout period) to receive TTFC for 8 weeks (TTFC group) or to continue beta-blocker monotherapy for 4 weeks followed by TTFC for the remaining 4 weeks (beta-blocker group). Results. The mean IOP (±standard deviation) at baseline in the TTFC and beta-blocker groups was 22.5 ± 2.5 mmHg and 22.2 ± 2.3 mmHg, respectively, and at weeks 4 and 8, was 16.7 ± 3.1 mmHg and 16.1 ± 3.1 mmHg, respectively, in TTFC group and 21.1 ± 3.1 mmHg and 16.1 ± 2.8 mmHg, respectively, in the beta-blocker group. There was a significant least squares mean difference between TTFC and beta-blocker in 8 a.m. IOP at week 4 (−4.6 mmHg; one-sided 95% confidence interval [−inf, −3.9]; p < 0.0001 [primary endpoint]); the upper bound of the 95% confidence interval was within the prespecified limit (<0). Both treatments were well tolerated. Conclusion. Superior IOP control was achieved with TTFC in patients with OAG or OHT previously uncontrolled with beta-blockers. No new safety findings were identified. This trial is registered with ClinicalTrials.gov NCT02003391. PMID:28239491

  6. Fixed-Dose Artesunate–Amodiaquine Combination vs Chloroquine for Treatment of Uncomplicated Blood Stage P. vivax Infection in the Brazilian Amazon: An Open-Label Randomized, Controlled Trial

    Science.gov (United States)

    Alencar, Aline C.; Melo, Gisely C.; Magalhaes, Belisa L.; Machado, Kim; Alencar Filho, Aristóteles C.; Kuehn, Andrea; Marques, Marly M.; Manso, Monica Costa; Felger, Ingrid; Vieira, José L. F.; Lameyre, Valerie; Daniel-Ribeiro, Claudio T.; Lacerda, Marcus V. G.

    2017-01-01

    Background. Despite increasing evidence of the development of Plasmodium vivax chloroquine (CQ) resistance, there have been no trials comparing its efficacy with that of artemisinin-based combination therapies (ACTs) in Latin America. Methods. This randomized controlled trial compared the antischizontocidal efficacy and safety of a 3-day supervised treatment of the fixed-dose combination artesunate-amodiaquine Winthrop® (ASAQ) versus CQ for treatment of uncomplicated P. vivax infection in Manaus, Brazil. Patients were followed for 42 days. Primary endpoints were adequate clinical and parasitological responses (ACPR) rates at day 28. Genotype-adjustment was performed. Results. From 2012 to 2013, 380 patients were enrolled. In the per-protocol (PP) analysis, adjusted-ACPR was achieved in 100% (165/165) and 93.6% (161/172) of patients in the ASAQ and CQ arm (difference 6.4%, 95% CI 2.7%; 10.1%) at day 28 and in 97.4% (151/155) and 77.7% (129/166), respectively (difference 19.7%, 95% CI 12.9%; 26.5%), at day 42. Apart from ITT D28 assessment, superiority of ASAQ on ACPR was demonstrated. ASAQ presented faster clearance of parasitaemia and fever. Based on CQ blood level measurements, CQ resistance prevalence was estimated at 11.5% (95% CI: 7.5-17.3) up to day 42. At least one emergent adverse event (AE) was recorded for 79/190 (41x6%) in the ASAQ group and for 85/190 (44x7%) in the CQ group. Both treatments had similar safety profiles. Conclusions. ASAQ exhibited high efficacy against CQ resistant P. vivax and is an adequate alternative in the study area. Studies with an efficacious comparator, longer follow-up and genotype-adjustment can improve CQR characterization. Clinical Trials Registration. NCT01378286. PMID:27988484

  7. Efficacy of fixed-dose combination artesunate-amodiaquine versus artemether-lumefantrine for uncomplicated childhood Plasmodium falciparum malaria in Democratic Republic of Congo: a randomized non-inferiority trial

    Directory of Open Access Journals (Sweden)

    Espié Emmanuelle

    2012-05-01

    Full Text Available Abstract Background In 2005, the Democratic Republic of Congo (DRC adopted artesunate and amodiaquine (ASAQ as first-line anti-malarial treatment. In order to compare the efficacy of the fixed-dose formulation ASAQ versus artemether-lumefantrine (AL, a randomized, non-inferiority open-label trial was conducted in Katanga. Methods Children aged six and 59 months with uncomplicated Plasmodium falciparum malaria were enrolled and randomly allocated into one of the two regimens. The risk of recurrent parasitaemia by day 42, both unadjusted and adjusted by PCR genotyping to distinguish recrudescence from new infection, was analysed. Results Between April 2008 and March 2009, 301 children were included: 156 with ASAQ and 145 with AL. No early treatment failures were reported. Among the 256 patients followed-up at day 42, 32 patients developed late clinical or parasitological failure (9.9% (13/131 in the ASAQ group and 15.2% (19/125 in the AL group. After PCR correction, cure rates were 98.3% (95%CI, 94.1-99.8 in the ASAQ group and 99.1% (95%CI, 94.9-99.9 in the AL group (difference −0.7%, one sided 95% CI −3.1. Kaplan-Meier PCR-adjusted cure rates were similar. Both treatment regimens were generally well tolerated. Conclusion Both ASAQ and AL are highly effective and currently adequate as the first-line treatment of uncomplicated falciparum malaria in this area of Katanga, DRC. However, in a very large country, such as DRC, and because of possible emergence of resistance from other endemic regions, surveillance of efficacy of artemisinin-based combination treatments, including other evaluations of the resistance of ASAQ, need to be done in other provinces. Trial registration The protocol was registered with the clinicaltrials.gov, open clinical trial registry under the identifier number NCT01567423.

  8. A double-blind, randomized, controlled trial to compare the efficacy and tolerability of fixed doses of ropinirole, bupropion, and iron in treatment of restless legs syndrome (Willis-Ekbom disease).

    Science.gov (United States)

    Vishwakarma, Kirti; Kalra, Juhi; Gupta, Ravi; Sharma, Mukesh; Sharma, Taruna

    2016-01-01

    We aimed to compare the efficacy of fixed doses of bupropion and ropinirole and iron alone for the treatment of restless legs syndrome (RLS) and to look for the tolerability of these medications. Patients diagnosed with RLS were randomly divided into three groups with thirty patients in each group (Group A: Bupropion [300 mg/day], Group B: Ropinirole [0.25-0.5 mg/day], and Group C: Oral iron [150 mg elemental iron] along with folic acid [500 μg]). Each participant was then assessed for severity of RLS, as well as RLS-related quality at the baseline, and thereafter, every 14(th) day till 6 weeks based on the International Restless Legs Scale (IRLS) severity rating scale and Restless Legs Syndrome Quality of Life (RLSQoL) Questionnaire, respectively. IRLS scores differed significantly from baseline visit to last (F = 4.85; P = 0.01). The interaction between the time x treatment group was significant (F = 10.37; P < 0.001) showing an improvement with the therapy in all the groups. Pair-wise comparison depicted that ropinirole group differed from other two groups in IRLS score (F = 7.06; P = 0.001), which were comparable to each other. Regarding quality of life of these cases, within each group scores differed among all the four visits (F = 5.12; P = 0.002). Unlike IRLS, there was no significant difference among the RLSQOL scores between groups at any point of time (F = 1.2; P = 0.28). RLS severity decreased across time in all three groups; however, the ropinirole treatment was better than the bupropion and iron-folate therapy. Moreover, RLS-related quality of life although improved among all groups, it was comparable among three groups.

  9. A double-blind, randomized, controlled trial to compare the efficacy and tolerability of fixed doses of ropinirole, bupropion, and iron in treatment of restless legs syndrome (Willis-Ekbom disease

    Directory of Open Access Journals (Sweden)

    Kirti Vishwakarma

    2016-01-01

    Full Text Available Background: We aimed to compare the efficacy of fixed doses of bupropion and ropinirole and iron alone for the treatment of restless legs syndrome (RLS and to look for the tolerability of these medications. Materials and Methods: Patients diagnosed with RLS were randomly divided into three groups with thirty patients in each group (Group A: Bupropion [300 mg/day], Group B: Ropinirole [0.25-0.5 mg/day], and Group C: Oral iron [150 mg elemental iron] along with folic acid [500 μg]. Each participant was then assessed for severity of RLS, as well as RLS-related quality at the baseline, and thereafter, every 14 th day till 6 weeks based on the International Restless Legs Scale (IRLS severity rating scale and Restless Legs Syndrome Quality of Life (RLSQoL Questionnaire, respectively. Results: IRLS scores differed significantly from baseline visit to last (F = 4.85; P = 0.01. The interaction between the time x treatment group was significant (F = 10.37; P < 0.001 showing an improvement with the therapy in all the groups. Pair-wise comparison depicted that ropinirole group differed from other two groups in IRLS score (F = 7.06; P = 0.001, which were comparable to each other. Regarding quality of life of these cases, within each group scores differed among all the four visits (F = 5.12; P = 0.002. Unlike IRLS, there was no significant difference among the RLSQOL scores between groups at any point of time (F = 1.2; P = 0.28. Conclusion: RLS severity decreased across time in all three groups; however, the ropinirole treatment was better than the bupropion and iron-folate therapy. Moreover, RLS-related quality of life although improved among all groups, it was comparable among three groups.

  10. A double-blind, randomized, controlled trial to compare the efficacy and tolerability of fixed doses of ropinirole, bupropion, and iron in treatment of restless legs syndrome (Willis–Ekbom disease)

    Science.gov (United States)

    Vishwakarma, Kirti; Kalra, Juhi; Gupta, Ravi; Sharma, Mukesh; Sharma, Taruna

    2016-01-01

    Background: We aimed to compare the efficacy of fixed doses of bupropion and ropinirole and iron alone for the treatment of restless legs syndrome (RLS) and to look for the tolerability of these medications. Materials and Methods: Patients diagnosed with RLS were randomly divided into three groups with thirty patients in each group (Group A: Bupropion [300 mg/day], Group B: Ropinirole [0.25–0.5 mg/day], and Group C: Oral iron [150 mg elemental iron] along with folic acid [500 μg]). Each participant was then assessed for severity of RLS, as well as RLS-related quality at the baseline, and thereafter, every 14th day till 6 weeks based on the International Restless Legs Scale (IRLS) severity rating scale and Restless Legs Syndrome Quality of Life (RLSQoL) Questionnaire, respectively. Results: IRLS scores differed significantly from baseline visit to last (F = 4.85; P = 0.01). The interaction between the time x treatment group was significant (F = 10.37; P < 0.001) showing an improvement with the therapy in all the groups. Pair-wise comparison depicted that ropinirole group differed from other two groups in IRLS score (F = 7.06; P = 0.001), which were comparable to each other. Regarding quality of life of these cases, within each group scores differed among all the four visits (F = 5.12; P = 0.002). Unlike IRLS, there was no significant difference among the RLSQOL scores between groups at any point of time (F = 1.2; P = 0.28). Conclusion: RLS severity decreased across time in all three groups; however, the ropinirole treatment was better than the bupropion and iron-folate therapy. Moreover, RLS-related quality of life although improved among all groups, it was comparable among three groups. PMID:27994356

  11. Validation and pharmacokinetic application of a high-performance liquid chromatographic technique for determining the concentrations of amodiaquine and its metabolite in plasma of patients treated with oral fixed-dose amodiaquine-artesunate combination in areas of malaria endemicity.

    Science.gov (United States)

    Adedeji, Olumuyiwa N; Bolaji, Oluseye O; Falade, Catherine O; Osonuga, Odusoga A; Ademowo, Olusegun G

    2015-09-01

    Artemisinin-based combination therapies (ACTs) have been adopted by most African countries, including Nigeria, as first-line treatments for uncomplicated falciparum malaria. Fixed-dose combinations of these ACTs, amodiaquine-artesunate (FDC AQAS) and artemether-lumefantrine (AL), were introduced in Nigeria to improve compliance and achieve positive outcomes of malaria treatment. In order to achieve clinical success with AQAS, we developed and validated a simple and sensitive high-performance liquid chromatography (HPLC) method with UV detection for determination of amodiaquine (AQ) and desethylamodiaquine (DAQ) in plasma using liquid-liquid extraction of the drugs with diethyl ether following protein precipitation with acetonitrile. Chromatographic separation was achieved using an Agilent Zorbax C18 column and a mobile phase consisting of distilled water-methanol (80:20 [vol/vol]) with 2% (vol/vol) triethylamine, pH 2.2, at a flow rate of 1 ml/min. Calibration curves in spiked plasma were linear from 100 to 1,000 ng/ml (r > 0.99) for both AQ and DAQ. The limit of detection was 1 ng (sample size, 20 μl). The intra- and interday coefficients of variation at 150, 300, and 900 ng/ml ranged from 1.3 to 4.8%, and the biases were between 6.4 and 9.5%. The mean extraction recoveries of AQ and DAQ were 80.0% and 68.9%, respectively. The results for the pharmacokinetic parameters of DAQ following oral administration of FDC AQAS (612/200 mg) for 3 days in female and male patients with uncomplicated falciparum malaria showed that the maximum plasma concentrations (C max) (740 ± 197 versus 767 ± 185 ng/ml), areas under the plasma concentration-time curve (AUC) (185,080 ± 20,813 versus 184,940 ± 16,370 h · ng/ml), and elimination half-life values (T 1/2) (212 ± 1.14 versus 214 ± 0.84 h) were similar (P > 0.05).

  12. Comparative efficacy of indacaterol 150 μg and 300 μg versus fixed-dose combinations of formoterol + budesonide or salmeterol + fluticasone for the treatment of chronic obstructive pulmonary disease – a network meta-analysis

    Science.gov (United States)

    Cope, Shannon; Capkun-Niggli, Gorana; Gale, Rupert; Jardim, José R; Jansen, Jeroen P

    2011-01-01

    Objective: To compare efficacy of indacaterol to that of fixed-dose combination (FDC) formoterol and budesonide (FOR/BUD) and FDC salmeterol and fluticasone (SAL/FP) for the treatment of chronic obstructive pulmonary disease (COPD) based on the available randomized clinical trials (RCTs). Methods: Fifteen placebo-controlled RCTs were included that evaluated: indacaterol 150 μg (n = 5 studies), indacaterol 300 μg (n = 4), FOR/BUD 9/160 μg (n = 2), FOR/BUD 9/320 μg (n = 3), SAL/FP 50/500 μg (n = 5), and SAL/FP 50/250 μg (n = 1). Outcomes of interest were trough forced expiratory volume in 1 second (FEV1), total scores for St. George’s Respiratory Questionnaire (SGRQ), and transition dyspnea index (TDI). All trials were analyzed simultaneously using a Bayesian network meta-analysis and relative treatment effects between all regimens were obtained. Treatment-by-covariate interactions were included where possible to improve the similarity of the trials. Results: Indacaterol 150 μg resulted in a higher change from baseline (CFB) in FEV1 at 12 weeks compared to FOR/BUD 9/160 μg (difference in CFB 0.11 L [95% credible intervals: 0.08, 0.13]) and FOR/BUD 9/320 μg (0.09 L [0.06, 0.11]) and was comparable to SAL/FP 50/250 μg (0.02 L [−0.04, 0.08]) and SAL/FP 50/500 μg (0.03 L [0.00, 0.06]). Similar results were observed for indacaterol 300 μg at 12 weeks and indacaterol 150/300 μg at 6 months. Indacaterol 150 μg demonstrated comparable improvement in SGRQ total score at 6 months versus FOR/BUD (both doses), and SAL/FP 50/500 μg (−2.16 point improvement [−4.96, 0.95]). Indacaterol 150 and 300 μg demonstrated comparable TDI scores versus SAL/FP 50/250 μg (0.21 points (−0.57, 0.99); 0.39 [−0.39, 1.17], respectively) and SAL/FP 50/500 μg at 6 months. Conclusion: Indacaterol monotherapy is expected to be at least as good as FOR/BUD (9/320 and 9/160 μg) and comparable to SAL/FP (50/250 and 50/500 μg) in terms of lung function. Indacaterol is also

  13. Comparative efficacy of indacaterol 150 μg and 300 μg versus fixed-dose combinations of formoterol + budesonide or salmeterol + fluticasone for the treatment of chronic obstructive pulmonary disease--a network meta-analysis.

    Science.gov (United States)

    Cope, Shannon; Capkun-Niggli, Gorana; Gale, Rupert; Jardim, José R; Jansen, Jeroen P

    2011-01-01

    To compare efficacy of indacaterol to that of fixed-dose combination (FDC) formoterol and budesonide (FOR/BUD) and FDC salmeterol and fluticasone (SAL/FP) for the treatment of chronic obstructive pulmonary disease (COPD) based on the available randomized clinical trials (RCTs). Fifteen placebo-controlled RCTs were included that evaluated: indacaterol 150 μg (n = 5 studies), indacaterol 300 μg (n = 4), FOR/BUD 9/160 μg (n = 2), FOR/BUD 9/320 μg (n = 3), SAL/FP 50/500 μg (n = 5), and SAL/FP 50/250 μg (n = 1). Outcomes of interest were trough forced expiratory volume in 1 second (FEV(1)), total scores for St. George's Respiratory Questionnaire (SGRQ), and transition dyspnea index (TDI). All trials were analyzed simultaneously using a Bayesian network meta-analysis and relative treatment effects between all regimens were obtained. Treatment-by-covariate interactions were included where possible to improve the similarity of the trials. Indacaterol 150 μg resulted in a higher change from baseline (CFB) in FEV(1) at 12 weeks compared to FOR/BUD 9/160 μg (difference in CFB 0.11 L [95% credible intervals: 0.08, 0.13]) and FOR/BUD 9/320 μg (0.09 L [0.06, 0.11]) and was comparable to SAL/FP 50/250 μg (0.02 L [-0.04, 0.08]) and SAL/FP 50/500 μg (0.03 L [0.00, 0.06]). Similar results were observed for indacaterol 300 μg at 12 weeks and indacaterol 150/300 μg at 6 months. Indacaterol 150 μg demonstrated comparable improvement in SGRQ total score at 6 months versus FOR/BUD (both doses), and SAL/FP 50/500 μg (-2.16 point improvement [-4.96, 0.95]). Indacaterol 150 and 300 μg demonstrated comparable TDI scores versus SAL/FP 50/250 μg (0.21 points (-0.57, 0.99); 0.39 [-0.39, 1.17], respectively) and SAL/FP 50/500 μg at 6 months. Indacaterol monotherapy is expected to be at least as good as FOR/BUD (9/320 and 9/160 μg) and comparable to SAL/FP (50/250 and 50/500 μg) in terms of lung function. Indacaterol is also expected to be comparable to FOR/BUD (9/320 and 9

  14. Comparative efficacy of indacaterol 150 µg and 300 µg versus fixed-dose combinations of formoterol + budesonide or salmeterol + fluticasone for the treatment of chronic obstructive pulmonary disease – a network meta-analysis

    Directory of Open Access Journals (Sweden)

    Cope S

    2011-06-01

    Full Text Available Shannon Cope1, Gorana Capkun-Niggli2, Rupert Gale3, José R Jardim4, Jeroen P Jansen11Mapi Values, Boston, MA, USA; 2Health Economics and Outcomes Research, Novartis Pharma AG, Basel, Switzerland; 3Novartis Horsham Research Centre, Horsham, UK; 4Respiratory Division, Federal University of São Paulo, BrazilObjective: To compare efficacy of indacaterol to that of fixed-dose combination (FDC formoterol and budesonide (FOR/BUD and FDC salmeterol and fluticasone (SAL/FP for the treatment of chronic obstructive pulmonary disease (COPD based on the available randomized clinical trials (RCTs.Methods: Fifteen placebo-controlled RCTs were included that evaluated: indacaterol 150 µg (n = 5 studies, indacaterol 300 µg (n = 4, FOR/BUD 9/160 µg (n = 2, FOR/BUD 9/320 µg (n = 3, SAL/FP 50/500 µg (n = 5, and SAL/FP 50/250 µg (n = 1. Outcomes of interest were trough forced expiratory volume in 1 second (FEV1, total scores for St. George's Respiratory Questionnaire (SGRQ, and transition dyspnea index (TDI. All trials were analyzed simultaneously using a Bayesian network meta-analysis and relative treatment effects between all regimens were obtained. Treatment-by-covariate interactions were included where possible to improve the similarity of the trials.Results: Indacaterol 150 µg resulted in a higher change from baseline (CFB in FEV1 at 12 weeks compared to FOR/BUD 9/160 µg (difference in CFB 0.11 L [95% credible intervals: 0.08, 0.13] and FOR/BUD 9/320 µg (0.09 L [0.06, 0.11] and was comparable to SAL/FP 50/250 µg (0.02 L [–0.04, 0.08] and SAL/FP 50/500 µg (0.03 L [0.00, 0.06]. Similar results were observed for indacaterol 300 µg at 12 weeks and indacaterol 150/300 µg at 6 months. Indacaterol 150 µg demonstrated comparable improvement in SGRQ total score at 6 months versus FOR/BUD (both doses, and SAL/FP 50/500 µg (–2.16 point improvement [–4.96, 0.95]. Indacaterol 150 and 300 µg demonstrated comparable TDI scores versus SAL/FP 50/250 µg

  15. Estimated rates of recurrence, cure, and treatment abandonment in patients with pulmonary tuberculosis treated with a -four-drug fixed-dose combination regimen at a tertiary health care facility in the city of Rio de Janeiro, Brazil.

    Science.gov (United States)

    Silva, Vangie Dias da; Mello, Fernanda Carvalho de Queiroz; Figueiredo, Sonia Catarina de Abreu

    2017-01-01

    To estimate the rates of recurrence, cure, and treatment abandonment in patients with pulmonary tuberculosis treated with a four-drug fixed-dose combination (FDC) regimen, as well as to evaluate possible associated factors. This was a retrospective observational study involving 208 patients with a confirmed diagnosis of pulmonary tuberculosis enrolled in the Hospital Tuberculosis Control Program at the Institute for Thoracic Diseases, located in the city of Rio de Janeiro, Brazil. Between January of 2007 and October of 2010, the patients were treated with the rifampin-isoniazid-pyrazinamide (RHZ) regimen, whereas, between November of 2010 and June of 2013, the patients were treated with the rifampin-isoniazid-pyrazinamide-ethambutol FDC (RHZE/FDC) regimen. Data regarding tuberculosis recurrence and mortality in the patients studied were retrieved from the Brazilian Case Registry Database and the Brazilian Mortality Database, respectively. The follow-up period comprised two years after treatment completion. The rates of cure, treatment abandonment, and death were 90.4%, 4.8%, and 4.8%, respectively. There were 7 cases of recurrence during the follow-up period. No significant differences in the recurrence rate were found between the RHZ and RHZE/FDC regimen groups (p = 0.13). We identified no factors associated with the occurrence of recurrence; nor were there any statistically significant differences between the treatment groups regarding adverse effects or rates of cure, treatment abandonment, or death. The adoption of the RHZE/FDC regimen produced no statistically significant differences in the rates of recurrence, cure, or treatment abandonment; nor did it have any effect on the occurrence of adverse effects, in comparison with the use of the RHZ regimen. Estimar as taxas de recidiva, cura e abandono de tratamento em pacientes com tuberculose pulmonar tratados com o esquema de dose fixa combinada (DFC) de quatro drogas e avaliar possíveis fatores associados

  16. Use of Fixed Dose Combination (FDC Drugs in India: Central Regulatory Approval and Sales of FDCs Containing Non-Steroidal Anti-Inflammatory Drugs (NSAIDs, Metformin, or Psychotropic Drugs.

    Directory of Open Access Journals (Sweden)

    Patricia McGettigan

    2015-05-01

    Full Text Available In 2012, an Indian parliamentary committee reported that manufacturing licenses for large numbers of fixed dose combination (FDC drugs had been issued by state authorities without prior approval of the Central Drugs Standard Control Organization (CDSCO in violation of rules, and considered that some ambiguity until 1 May 2002 about states' powers might have contributed. To our knowledge, no systematic enquiry has been undertaken to determine if evidence existed to support these findings. We investigated CDSCO approvals for and availability of oral FDC drugs in four therapeutic areas: analgesia (non-steroidal anti-inflammatory drugs [NSAIDs], diabetes (metformin, depression/anxiety (anti-depressants/benzodiazepines, and psychosis (anti-psychotics.This was an ecologic study with a time-trend analysis of FDC sales volumes (2007-2012 and a cross-sectional examination of 2011-2012 data to establish the numbers of formulations on the market with and without a record of CDSCO approval ("approved" and "unapproved", their branded products, and sales volumes. Data from the CDSCO on approved FDC formulations were compared with sales data from PharmaTrac, a database of national drug sales. We determined the proportions of FDC sales volumes (2011-2012 arising from centrally approved and unapproved formulations and from formulations including drugs banned/restricted internationally. We also determined the proportions of centrally approved and unapproved formulations marketed before and after 1 May 2002, when amendments were made to the drug rules. FDC approvals in India, the United Kingdom (UK, and United States of America (US were compared. For NSAID FDCs, 124 formulations were marketed, of which 34 (27% were centrally approved and 90 (73% were unapproved; metformin: 25 formulations, 20 (80% approved, five (20% unapproved; anti-depressants/benzodiazepines: 16 formulations, three (19% approved, 13 (81% unapproved; anti-psychotics: ten formulations, three (30

  17. Evaluating dose response from flexible dose clinical trials

    Directory of Open Access Journals (Sweden)

    Baron David

    2008-01-01

    Full Text Available Abstract Background The true dose effect in flexible-dose clinical trials may be obscured and even reversed because dose and outcome are related. Methods To evaluate dose effect in response on primary efficacy scales from 2 randomized, double-blind, flexible-dose trials of patients with bipolar mania who received olanzapine (N = 234, 5–20 mg/day, or patients with schizophrenia who received olanzapine (N = 172, 10–20 mg/day, we used marginal structural models, inverse probability of treatment weighting (MSM, IPTW methodology. Dose profiles for mean changes from baseline were evaluated using weighted MSM with a repeated measures model. To adjust for selection bias due to non-random dose assignment and dropouts, patient-specific time-dependent weights were determined as products of (i stable weights based on inverse probability of receiving the sequence of dose assignments that was actually received by a patient up to given time multiplied by (ii stable weights based on inverse probability of patient remaining on treatment by that time. Results were compared with those by unweighted analyses. Results While the observed difference in efficacy scores for dose groups for the unweighted analysis strongly favored lower doses, the weighted analyses showed no strong dose effects and, in some cases, reversed the apparent "negative dose effect." Conclusion While naïve comparison of groups by last or modal dose in a flexible-dose trial may result in severely biased efficacy analyses, the MSM with IPTW estimators approach may be a valuable method of removing these biases and evaluating potential dose effect, which may prove useful for planning confirmatory trials.

  18. Weight-based pricing in the collection of household waste : the Oostzaan case

    NARCIS (Netherlands)

    Linderhof, V.; Kooreman, P.; Allers, M.A.; Wiersma, D.

    2001-01-01

    This paper provides an empirical analysis of the effects of weight-based pricing in the collection of household waste. Using a comprehensive panel data set on all households in a Dutch municipality we estimate short-run as well as long-run price effects for the amounts of both compostable and non-re

  19. Associations of weight-based teasing and emotional well-being among adolescents.

    Science.gov (United States)

    Eisenberg, Marla E; Neumark-Sztainer, Dianne; Story, Mary

    2003-08-01

    Verbal harassment, such as bullying and hate speech, has received considerable attention recently, but less is known about weight-based teasing and its potential harmful effects on young people's psychosocial well-being. To determine the associations of weight-based teasing and body satisfaction, self-esteem, depressive symptoms, and suicidal ideation and suicide attempts using a large sample of adolescents. Secondary analysis of survey and anthropometric data. Ethnically and socioeconomically diverse communities in the urban and suburban school districts of the Minneapolis/St Paul metropolitan area. A school-based sample of 4746 adolescents in grades 7 to 12 at 31 public middle schools and high schools. Weight-based teasing from peers or family members, body satisfaction, self-esteem, depressive symptoms, and suicidal ideation and suicide attempts. Of the eligible students, 81.5% participated; 30.0% of adolescent girls and 24.7% of adolescent boys were teased by peers, and 28.7% of adolescent girls and 16.1% of adolescent boys were teased by family members. Approximately 14.6% of adolescent girls and 9.6% of adolescent boys reported teasing from both of these sources. Teasing about body weight was consistently associated with low body satisfaction, low self-esteem, high depressive symptoms, and thinking about and attempting suicide, even after controlling for actual body weight. These associations held for adolescent boys and girls, across racial, ethnic, and weight groups. Furthermore, teasing from 2 sources was associated with a higher prevalence of emotional health problems than either teasing from a single source or no teasing. Physicians and other health care providers should recognize the importance of weight-based teasing for young patients. Policy, programs, and education should focus on increasing awareness of what constitutes weight-based teasing, its potentially harmful effects on adolescents' emotional well-being, and reduction of this behavior.

  20. QCD at Fixed Topology

    CERN Document Server

    Brower, Richard C; Negele, John W; Wiese, U J

    2003-01-01

    Since present Monte Carlo algorithms for lattice QCD may become trapped in a fixed topological charge sector, it is important to understand the effect of calculating at fixed topology. In this work, we show that although the restriction to a fixed topological sector becomes irrelevant in the infinite volume limit, it gives rise to characteristic finite size effects due to contributions from all $\\theta$-vacua. We calculate these effects and show how to extract physical results from numerical data obtained at fixed topology.

  1. Performance Evaluation of Stable Weight-Based on Demand Routing Protocol for Mobile Ad Hoc Network

    Directory of Open Access Journals (Sweden)

    Oon C. Hsi

    2009-01-01

    Full Text Available Problem statement: A MANET is an autonomous collection of mobile users that communicate over relatively bandwidth constrained wireless links. Since the nodes are mobile, the network topology may change rapidly and unpredictably over time. Approach: A Stable Weight-based On demand Routing Protocol (SWORP that uses the weight-based route strategy to select a stable route was created by Wang. But SWORP only evaluated in a limited setting of simulation, more simulation parameter have to test with SWORP to evaluate how far this protocol can go on. In this project, SWORP was implemented in simulation environment with two other routing protocols, AODV and DSR. Results: These three protocols were implemented in Network Simulator 2 (NS2 and the performance was compare with performance metrics, end-to-end delay, number of packet drop and packet delivery ratio. Conclusion: As expected, SWORP had outperformed AODV and DSR in the overall routing performance.

  2. Weight-based nutritional diagnosis of Mexican children and adolescents with neuromotor disabilities

    OpenAIRE

    2012-01-01

    Abstract Background Nutrition related problems are increasing worldwide but they have scarcely been evaluated in people with neuromotor disabilities, particularly in developing countries. In this study our aim was to describe the weight-based nutritional diagnoses of children and adolescents with neuromotor disabilities who attended a private rehabilitation center in Mexico City. Methods Data from the first visit’s clinical records of 410 patients who attended the Nutrition department at the ...

  3. A Study to Improve the Method of Ascertaining Attribute Weight Based on Rough Sets Theory

    Institute of Scientific and Technical Information of China (English)

    LIU Cheng; ZHANG Jian-bin; BAO Xin-zhong

    2009-01-01

    There are some shortages to ascertain attribute weight based on rough set in current studies. In this paper, attrib- ute importance represented by rough set is studied deeply. Aiming at the existing problems, algebra presentation of rough sets is proved to be more comprehensive than its information presentation, then a new method of ascertaining attribute weigh is put forward based on rough set conditional entropy. Finally, it is shown that the new method is more reasonable than the old one by an example.

  4. Emotional Implications of Weight Stigma Across Middle School: The Role of Weight-Based Peer Discrimination.

    Science.gov (United States)

    Juvonen, Jaana; Lessard, Leah M; Schacter, Hannah L; Suchilt, Luisana

    2017-01-01

    This study considered the emotional consequences of weight stigmatization in early adolescence by examining the effects of weight-based peer discrimination across middle school. Sampled across 26 urban middle schools, 5,128 youth (52% girls) with complete body mass index data at sixth or 7th grade were included: 30% Latino, 21% White, 14% East/Southeast Asian, 14% Multiethnic, 12% African American/Black, and 9% from other specific ethnic groups. About one third of the sample reported at least one weight-discrimination incident at 7th grade. Controlling for sixth-grade adjustment, perceptions of weight-based peer discrimination at 7th grade were stronger predictors of body dissatisfaction, social anxiety, and loneliness (and somatic symptoms for girls but not boys) at 8th-grade than 7th-grade body mass index. Moreover, heavier body stature during the 1st year in middle school was associated with increased body dissatisfaction by the end of middle school in part due to weight-related disrespectful, exclusionary, and demeaning treatment by peers. Weight-based peer discrimination helps us understand one of the stigmatizing mechanisms underlying the relation between heavy body stature and the progression of emotional problems in early adolescence.

  5. Fixed mobile convergence handbook

    CERN Document Server

    Ahson, Syed A

    2010-01-01

    From basic concepts to future directions, this handbook provides technical information on all aspects of fixed-mobile convergence (FMC). The book examines such topics as integrated management architecture, business trends and strategic implications for service providers, personal area networks, mobile controlled handover methods, SIP-based session mobility, and supervisory and notification aggregator service. Case studies are used to illustrate technical and systematic implementation of unified and rationalized internet access by fixed-mobile network convergence. The text examines the technolo

  6. Optically fixed photorefractive correlator

    Institute of Scientific and Technical Information of China (English)

    刘友文; 刘立人; 周常河; 徐良瑛

    2002-01-01

    An optically fixed photorefractive correlator is presented, where two-centre non-volatile holographic recording isemployed to write and fix the matched filter in doubly doped LiNbO3 crystals. This correlator shows good correlationcharacteristics and insensitivity to the writing beam during readout. It can be used in cases requiring stability and notrequiring modification for a long period, and it is refreshed optically when new information needs to be registered.

  7. Combating weight-based cyberbullying on Facebook with the dissenter effect.

    Science.gov (United States)

    Anderson, Jenn; Bresnahan, Mary; Musatics, Catherine

    2014-05-01

    Weight-based cyberbullying is prevalent among youth and adolescents and can have lasting negative psychological effects on the victims. One way to combat these negative effects is through modeling dissenting behavior. When a bystander challenges the bully or supports the victim, this models dissenting behavior. In this study, 181 participants were exposed to message manipulations posted on a Facebook page aimed at testing the conformity effect, the dissenter effect, and the bystander effect in response to enactment of weight-based bullying. Facebook is a common social media site where cyberbullying is reported. Results indicate that in the dissenting condition, participants' comments were significantly more positive or supporting for the victim, as compared to other conditions. This effect was more pronounced for men than for women. In addition, in the dissenting condition, men were less likely to consider the victim unhealthy than women and men in other conditions. These results support the effectiveness of efforts to model dissenting behavior in the face of bullies and extend them to online contexts. Implications are discussed.

  8. A comparative study of itraconazole in various dose schedules in the treatment of pulmonary aspergilloma in treated patients of pulmonary tuberculosis

    Directory of Open Access Journals (Sweden)

    Prahlad Rai Gupta

    2015-01-01

    Full Text Available Introduction: The optimal dose, duration, and efficacy of itraconazole in Indian patients of pulmonary aspergilloma (PA are not clearly defined. Therefore, a study was carried out, to resolve these issues in diagnosed cases of PA complicating old treated patients of pulmonary tuberculosis. Materials and Methods: The study patients randomly received itraconazole either in a fixed dose schedule of 200 mg (group I, 200 mg twice daily (group II or a variable dose schedule (group III, for 12 months. All the patients were followed up for the entire duration of the study for clinical, radiological, and immunological response. The side effects were recorded as and when reported by the patients and managed symptomatically. Results: A total of 60 patients were enrolled, 20, in each group. There were no intergroup differences with regard to age, sex, body weight, smoking status, alcohol intake, symptoms, Potassium hydroxide (KOH mount, fungal culture, pattern of radiological lesions or anti-aspergillus antibodies (anti-Asp-Ab titers. The radiological response was poor in group I patients, as compared to the other groups, at two months (P < 0.05. The dose of itraconazole was increased in five of the patients in group I due to poor response. A higher number of group II patients suffered side effects and the dose of itraconazole had to be decreased in three of these patients, but none of the patients on a variable dose schedule required a change in dose schedule. Conclusion: Thus, a weight-based variable dose schedule of itraconazole was found to be a more effective and safer modality in the management of PA than a fixed dose schedule.

  9. A method for determining customer requirement weights based on TFMF and TLR

    Science.gov (United States)

    Ai, Qingsong; Shu, Ting; Liu, Quan; Zhou, Zude; Xiao, Zheng

    2013-11-01

    'Customer requirements' (CRs) management plays an important role in enterprise systems (ESs) by processing customer-focused information. Quality function deployment (QFD) is one of the main CRs analysis methods. Because CR weights are crucial for the input of QFD, we developed a method for determining CR weights based on trapezoidal fuzzy membership function (TFMF) and 2-tuple linguistic representation (TLR). To improve the accuracy of CR weights, we propose to apply TFMF to describe CR weights so that they can be appropriately represented. Because the fuzzy logic is not capable of aggregating information without loss, TLR model is adopted as well. We first describe the basic concepts of TFMF and TLR and then introduce an approach to compute CR weights. Finally, an example is provided to explain and verify the proposed method.

  10. Fixed drug eruption due to paracetamol

    Directory of Open Access Journals (Sweden)

    Anjali Kushwah

    2013-12-01

    Full Text Available Fixed drug eruption is a common type of drug eruption seen in dermatology OPD’s. Usually it is seen with sulphonamides, salicylates, tetracyclines, oxyphenbutazones, dapsone, barbiturates, phenolphthalein, morphine, codeine, quinine, phenacetin, erythromycin, griseofulvin, mebendazole etc. We hereby report a case of fixed drug eruption due to single dose of oral paracetamol in an otherwise healthy male after one hour of consuming it. A provisional diagnosis of Paracetamol induced fixed drug eruption was made. Paracetamol was stopped and patient advised never to take Paracetamol in future. Patient was managed with prednisolone 10mg /day, cetirizine 10 mg/day, and amoxicillin 500 mg twice a day and mometasone + fusidic acid cream to be applied over the lesions. [Int J Basic Clin Pharmacol 2013; 2(6.000: 833-835

  11. Fixing Dataset Search

    Science.gov (United States)

    Lynnes, Chris

    2014-01-01

    Three current search engines are queried for ozone data at the GES DISC. The results range from sub-optimal to counter-intuitive. We propose a method to fix dataset search by implementing a robust relevancy ranking scheme. The relevancy ranking scheme is based on several heuristics culled from more than 20 years of helping users select datasets.

  12. Efficacy and safety of oral SK3530 for the treatment of erectile dysfunction in Korean men: a multicenter, randomized, double- blind, placebo-controlled, fixed dose, parallel group clinical trial

    Institute of Scientific and Technical Information of China (English)

    Jae-Seung Paick; Kwanjin Park; Hyonggi Jung; Nam-Cheol Park; Hyung-Ki Choi; Sae-Chul Kim; Tai-Young Ahn; Je-Jong Kim; Jong-Kwan Park; Kwang-Sung Park; Sung-Won Lee; Sae-Woong Kim

    2008-01-01

    Aim: To evaluate the efficacy and safety of SK3530, a newly developed type 5 phosphodiesterase inhibitor (PDE5I), in Korean men with erectile dysfunction (ED). Methods: A total of 119 patients were randomized at 10 centers in Korea to receive either SK3530 (50, 100, or 150 mg; n = 89) or placebo (n = 30) taken 1 h before anticipated sexual activity for an 8-week period. The patients were evaluated at baseline and 4 and 8 weeks after beginning therapy. Efficacy was assessed using the International Index of Erectile Function (IIEF), Sexual Encounter Profile (SEP), and the Global Assessment Question (GAQ). Safety was analyzed by adverse events, laboratory values and vital signs. Results: At the end of the study, all the primary and secondary efficacy end-points were statistically significantly improved by SK3530 compared with placebo (P < 0.05). Of the 89 patients in the treatment arm, 36 (42.3 %) achieved normal erectile mfunction after treatment, including six patients with severe ED. Treatment-related adverse events occurred in 32 patients.The most common adverse events were flushing, headache, dizziness and eye redness (10.9%, 7.6%, 2.5% and 2.5%, respectively), and most were mild. Only two patients discontinued treatment during the study period because of adverse events. Conclusion: The results of our phase Ⅱ study have confirmed the efficacy and safety of SK3530 in a broad population of men with ED of various etiologies and severity. The optimal doses in terms of efficacy and safety were determined to be 50 mg and 100 mg, respectively.

  13. 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

    Directory of Open Access Journals (Sweden)

    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.

  14. Efficacy and safety of duloxetine for treatment of fibromyalgia in patients with or without major depressive disorder: Results from a 6-month, randomized, double-blind, placebo-controlled, fixed-dose trial.

    Science.gov (United States)

    Russell, I Jon; Mease, Philip J; Smith, Timothy R; Kajdasz, Daniel K; Wohlreich, Madelaine M; Detke, Michael J; Walker, Daniel J; Chappell, Amy S; Arnold, Lesley M

    2008-06-01

    The primary objectives of this study were to assess the efficacy and safety of duloxetine for reducing pain severity in fibromyalgia patients with or without current major depressive disorder. This was a 6-month, multicenter, randomized, double-blind, placebo-controlled study. In total, 520 patients meeting American College of Rheumatology criteria for fibromyalgia were randomly assigned to duloxetine (20 mg/day, 60 mg/day, or 120 mg/day) or placebo, administered once daily, for 6 months (after 3 months, the duloxetine 20-mg/day group titrated to 60 mg/day). The co-primary outcome measures were the Brief Pain Inventory (BPI) average pain severity score and Patient Global Impressions of Improvement (PGI-I) score. Safety was assessed via treatment-emergent adverse events, and changes in vital sign, laboratory, and ECG measures. Compared with placebo-treated patients, those patients treated with duloxetine 120 mg/day improved significantly more on the co-primary outcome measures at 3 months (change in BPI score [-2.31 vs -1.39, Ptreatment with duloxetine 60 mg/day also significantly improved the co-primary measures at 3 months and BPI at 6 months. Duloxetine was efficacious in patients both with and without major depressive disorder. There were no clinically significant differences between treatment groups in changes in vital signs, laboratory measures, or ECG measures. Study results demonstrated that duloxetine at doses of 60 mg/day and 120 mg/day appears to be safe and efficacious in patients with fibromyalgia.

  15. 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

    Directory of Open Access Journals (Sweden)

    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

  16. Improving anti-bullying laws and policies to protect youth from weight-based victimization: parental support for action.

    Science.gov (United States)

    Puhl, R M; Suh, Y; Li, X

    2017-04-01

    Weight-based bullying is a prevalent problem among youth with overweight and obesity, but remains neglected in existing policy-level strategies to address youth bullying. Parental support is an influential catalyst motivating political will for policy decisions affecting youth, but has received limited research attention. To assess levels of, and predictors of, parental support for school-based policies and state/federal legal measures to address weight-based bullying in 2014 and 2015. Identical online questionnaires were completed by two independent national samples of parents in 2014 and 2015 (N = 1804). Parental support for all policy actions was high (at least 81%) and significantly increased from 2014 to 2015 for legal measures that would a) require state anti-bullying laws to add protections against weight-based bullying, and b) enact a federal anti-bullying law that includes weight-based bullying. These findings can inform policy discourse about remedies for youth bullying, and suggest that parental support for improved legal protections against weight-based bullying is present, consistent, and strong. © 2016 World Obesity Federation.

  17. Fixed textile shutters

    Directory of Open Access Journals (Sweden)

    K.A. Chernova

    2010-06-01

    Full Text Available One of the main socio-economic problems in Russia is the high cost and the poor condition of housing.Such goals as cost reduction, reducing installation time and increasing the service life of structures are accomplishing by creating new technologies of erecting buildings and developing ways ofquickconstruction, using different types of fixed formwork. One of themis textstone.Textstone is an artificial construction stone, containing on the outer surface the reinforcing fine-mesh shell with multifunctional properties, formed by the interwoven threads of a vigorous fixed formwork textile material (basalt, linen, silica and other glass yarns adhered by binding material. The innovative construction technology of production and installation of a new generation of textstone buildings has been registered as a brand TextStone. The fundamental difference between texstone and reinforced concrete and all known building materials is that the whole outer surface of solidified light binders is protected by strong, vigorous and fixed formwork made from inexpensive textile materials. Manufacturing textile shells allows using it as an internal finishing material, reducing or eliminating the cost of finishing work.The use of fixed textile construction shutters during the construction of buildings has obvious technical, economic, operational, sanitary and environmental benefits: short construction time (from 3 to 10 days, compact packaging and light weight of fabric shells, high fire resistance, frost resistance, ease of engineering services installation in the hollow communicating shells; minimal amount of finishing, roofing, heat and noise insulation works. Texstone is a durable solid monolithic construction that provides high viability and earthquakes, hurricanes wind, solar sultriness and frost resistance. Material complies with all sanitary and environmental requirements. Due to such physical, mechanical, operational, sanitary and ecological characteristics

  18. Fixed Sagittal Plane Imbalance

    OpenAIRE

    Savage, Jason W.; Patel, Alpesh A.

    2014-01-01

    Study Design Literature review. Objective To discuss the evaluation and management of fixed sagittal plane imbalance. Methods A comprehensive literature review was performed on the preoperative evaluation of patients with sagittal plane malalignment, as well as the surgical strategies to address sagittal plane deformity. Results Sagittal plane imbalance is often caused by de novo scoliosis or iatrogenic flat back deformity. Understanding the etiology and magnitude of sagittal malalignment is ...

  19. Weight-based contrast administration in the computerized tomography evaluation of acute pulmonary embolism

    Science.gov (United States)

    Laurent, Lisa; Zamfirova, Ina; Sulo, Suela; Baral, Pesach

    2017-01-01

    Abstract Compare individualized contrast protocol, or weight-based protocol, to standard methodology in evaluating acute pulmonary embolism. Retrospective chart review was performed on patients undergoing computed tomography angiography with standard contrast protocol (n = 50) or individualized protocol (n = 50). Computerized tomography images were assessed for vascular enhancement and image quality. Demographics were comparable, however, more patients in the individualized group were admitted to intensive care unit (48% vs 16%, P = 0.004). Vascular enhancement and image quality were also comparable, although individualized protocol had significantly fewer contrast and motion artifact limitations (28% vs 48%, P = 0.039). Fifteen percent decrease in intravenous contrast volume was identified in individualized group with no compromise in image quality. Individualized contrast protocol provided comparable vascular enhancement and image quality to the standard, yet with fewer limitations and lower intravenous contrast volume. Catheter-gauge flow rate restrictions resulting in inconsistent technologist exam execution were identified, supporting the need for further investigation of this regimen. PMID:28151887

  20. Design a Weight Based sorting distortion algorithm using Association rule Hiding for Privacy Preserving Data mining

    Directory of Open Access Journals (Sweden)

    R.Sugumar

    2011-12-01

    Full Text Available The security of the large database that contains certain crucial information, it will become a serious issue when sharing data to the network against unauthorized access. Privacy preserving data mining is a new research trend in privacy data for data mining and statistical database. Association analysis is a powerful tool for discovering relationships which are hidden in large database. Association rules hiding algorithms get strong an efficient performance for protecting confidential and crucial data. Data modification and rule hiding is one of the most important approaches for secure data. The objective of the proposed Weight Based Sorting Distortion (WBSD algorithm is to distort certain data which satisfies a particular sensitive rule. Then hide those transactions which support a sensitive rule and assigns them a priority and sorts them in ascending order according to the priority value of each rule. Then it uses these weights to compute the priority value for each transaction according to how weak the rule is that a transaction supports. Data distortion is one of the important methods to avoid this kind of scalability issues

  1. Fixed-Term Homotopy

    Directory of Open Access Journals (Sweden)

    Hector Vazquez-Leal

    2013-01-01

    Full Text Available A new tool for the solution of nonlinear differential equations is presented. The Fixed-Term Homotopy (FTH delivers a high precision representation of the nonlinear differential equation using only a few linear algebraic terms. In addition to this tool, a procedure based on Laplace-Padé to deal with the truncate power series resulting from the FTH method is also proposed. In order to assess the benefits of this proposal, two nonlinear problems are solved and compared against other semianalytic methods. The obtained results show that FTH is a power tool capable of generating highly accurate solutions compared with other methods of literature.

  2. Weight-based nutritional diagnosis of Mexican children and adolescents with neuromotor disabilities

    Directory of Open Access Journals (Sweden)

    Vega-Sanchez Rodrigo

    2012-07-01

    Full Text Available Abstract Background Nutrition related problems are increasing worldwide but they have scarcely been evaluated in people with neuromotor disabilities, particularly in developing countries. In this study our aim was to describe the weight-based nutritional diagnoses of children and adolescents with neuromotor disabilities who attended a private rehabilitation center in Mexico City. Methods Data from the first visit’s clinical records of 410 patients who attended the Nutrition department at the Teleton Center for Children Rehabilitation, between 1999 and 2008, were analyzed. Sex, age, weight and height, length or segmental length data were collected and used to obtain the nutritional diagnosis based on international growth charts, as well as disability-specific charts. Weight for height was considered the main indicator. Results Cerebral palsy was the most frequent diagnosis, followed by spina bifida, muscular dystrophy, and Down’s syndrome. Children with cerebral palsy showed a higher risk of presenting low weight/undernutrition (LW/UN than children with other disabilities, which was three times higher in females. In contrast, children with spina bifida, particularly males, were more likely to be overweight/obese (OW/OB, especially after the age of 6 and even more after 11. Patients with muscular dystrophy showed a significantly lower risk of LW/UN than patients with other disabilities. In patients with Down’s syndrome neither LW/UN nor OW/OB were different between age and sex. Conclusions This is the first study that provides evidence of the nutritional situation of children and adolescents with neuromotor disabilities in Mexico, based on their weight status. Low weight and obesity affect a large number of these patients due to their disability, age and sex. Early nutritional diagnosis must be considered an essential component in the treatment of these patients to prevent obesity and malnutrition, and improve their quality of life.

  3. Fixed and Sunk Costs Revisited.

    Science.gov (United States)

    Wang, X. Henry; Yang, Bill Z.

    2001-01-01

    Attempts to clarify the concepts of, and the link between, fixed costs and sunk costs. Argues that the root of confusion is the inconsistency in defining the term fixed costs. Consistently defines fixed and sunk costs, and describes how instructors must teach under these definitions. (RLH)

  4. Fixed sagittal plane imbalance.

    Science.gov (United States)

    Savage, Jason W; Patel, Alpesh A

    2014-12-01

    Study Design Literature review. Objective To discuss the evaluation and management of fixed sagittal plane imbalance. Methods A comprehensive literature review was performed on the preoperative evaluation of patients with sagittal plane malalignment, as well as the surgical strategies to address sagittal plane deformity. Results Sagittal plane imbalance is often caused by de novo scoliosis or iatrogenic flat back deformity. Understanding the etiology and magnitude of sagittal malalignment is crucial in realignment planning. Objective parameters have been developed to guide surgeons in determining how much correction is needed to achieve favorable outcomes. Currently, the goals of surgery are to restore a sagittal vertical axis Sagittal plane malalignment is an increasingly recognized cause of pain and disability. Treatment of sagittal plane imbalance varies according to the etiology, location, and severity of the deformity. Fixed sagittal malalignment often requires complex reconstructive procedures that include osteotomy correction. Reestablishing harmonious spinopelvic alignment is associated with significant improvement in health-related quality-of-life outcome measures and patient satisfaction.

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

    African Journals Online (AJOL)

    Esem

    Medical Journal of Zambia, Vol. 38, No. 3 (2011) ... medicines are a threat to health and the risks they. 13 ... Anti Tuberculosis Drugs in Public and Private Health ... University of Zambia, School of Medicine, Department of Community Medicine,.

  6. Fixed-dose combination therapy in hypertension: pros.

    Science.gov (United States)

    Taddei, Stefano

    2012-06-01

    Effective treatment of high blood pressure represents a key strategy for reducing the burden of hypertension-related cardiovascular diseases, mostly myocardial infarction and stroke. Despite these well established concepts, however, hypertension remains poorly controlled, worldwide. In addition, treated hypertensive patients often remain at higher risk compared with the normotensive population, even when a satisfactory blood pressure control is achieved, due to the high or very high added cardiovascular risk profile observed in these patients. An emerging strategy to improve blood pressure control and achieve this unmet target for cardiovascular disease prevention in hypertensive patients is represented by a more extensive use of rational and effective combination therapies with respect to monotherapy. Such an approach has been recently proposed even as first-line strategy in hypertensive patients at high added cardiovascular risk or in those in whom strict blood pressure control is required. Within the possible antihypertensive drug combinations currently available for the clinical management of hypertension, those based on the association of drugs inhibiting the renin-angiotensin system and thiazide diuretics or calcium channel blockers have demonstrated to be effective and safe in lowering both systolic and diastolic blood pressure levels with a good tolerability profile. In addition, these strategies have provided evidence for effective cardiovascular protection compared with conventional antihypertensive therapies. Among the antihypertensive drugs able to counteract the deleterious effects of abnormal activation of the renin-angiotensin system, angiotensin II receptor blockers have demonstrated to provide better tolerability profile and greater cardiovascular protection on hypertension-related organ damage compared with ACE inhibitors in randomized controlled clinical trials, in the presence of similar antihypertensive efficacy and safety. In particular, these drugs are characterized by lower rates of drug-related side effects, better compliance and adherence to prescribed antihypertensive regimens, and use in synergistic and rational combination therapies, all factors that may contribute to improve blood pressure control and reduce discontinuations from antihypertensive therapy in treated hypertensive patients.

  7. Efficacy and safety of fixed-dose combination therapy with olmesartan medoxomil and rosuvastatin in Korean patients with mild to moderate hypertension and dyslipidemia: an 8-week, multicenter, randomized, double-blind, factorial-design study (OLSTA-D RCT: OLmesartan rosuvaSTAtin from Daewoong).

    Science.gov (United States)

    Park, Jin-Sun; Shin, Joon-Han; Hong, Taek-Jong; Seo, Hong-Seog; Shim, Wan-Joo; Baek, Sang-Hong; Jeong, Jin-Ok; Ahn, Youngkeun; Kang, Woong-Chol; Kim, Young-Hak; Kim, Sang-Hyun; Hyon, Min-Su; Choi, Dong-Hoon; Nam, Chang-Wook; Park, Tae-Ho; Lee, Sang-Chol; Kim, Hyo-Soo

    2016-01-01

    The pill burden of patients with hypertension and dyslipidemia can result in poor medication compliance. This study aimed to evaluate the efficacy and safety of fixed-dose combination (FDC) therapy with olmesartan medoxomil (40 mg) and rosuvastatin (20 mg) in Korean patients with mild to moderate hypertension and dyslipidemia. This multicenter, randomized, double-blind, factorial-design study included patients aged ≥20 years with mild to moderate essential hypertension and dyslipidemia. Patients were randomly assigned to receive FDC therapy (40 mg olmesartan medoxomil, 20 mg rosuvastatin), 40 mg olmesartan medoxomil, 20 mg rosuvastatin, or a placebo. The percentage change from baseline in low-density lipoprotein cholesterol levels was compared between FDC therapy and olmesartan medoxomil, and the change from baseline in diastolic blood pressure was compared between FDC therapy and rosuvastatin 8 weeks after treatment. A total of 162 patients were included. The least square mean percentage change (standard error) from baseline in low-density lipoprotein cholesterol levels 8 weeks after treatment was significantly greater in the FDC than in the olmesartan medoxomil group (-52.3% [2.8%] vs -0.6% [3.5%], Polmesartan medoxomil and rosuvastatin is an effective, safe treatment for patients with hypertension and dyslipidemia. This combination may improve medication compliance in patients with a large pill burden.

  8. Fixed Access Network Sharing

    Science.gov (United States)

    Cornaglia, Bruno; Young, Gavin; Marchetta, Antonio

    2015-12-01

    Fixed broadband network deployments are moving inexorably to the use of Next Generation Access (NGA) technologies and architectures. These NGA deployments involve building fiber infrastructure increasingly closer to the customer in order to increase the proportion of fiber on the customer's access connection (Fibre-To-The-Home/Building/Door/Cabinet… i.e. FTTx). This increases the speed of services that can be sold and will be increasingly required to meet the demands of new generations of video services as we evolve from HDTV to "Ultra-HD TV" with 4k and 8k lines of video resolution. However, building fiber access networks is a costly endeavor. It requires significant capital in order to cover any significant geographic coverage. Hence many companies are forming partnerships and joint-ventures in order to share the NGA network construction costs. One form of such a partnership involves two companies agreeing to each build to cover a certain geographic area and then "cross-selling" NGA products to each other in order to access customers within their partner's footprint (NGA coverage area). This is tantamount to a bi-lateral wholesale partnership. The concept of Fixed Access Network Sharing (FANS) is to address the possibility of sharing infrastructure with a high degree of flexibility for all network operators involved. By providing greater configuration control over the NGA network infrastructure, the service provider has a greater ability to define the network and hence to define their product capabilities at the active layer. This gives the service provider partners greater product development autonomy plus the ability to differentiate from each other at the active network layer.

  9. Weight-based policy of hepatitis B vaccination in very low birth weight infants in Taiwan: a retrospective cross-sectional study.

    Directory of Open Access Journals (Sweden)

    Chien-Yi Chen

    Full Text Available BACKGROUND: The current recommendation of giving the first dose of hepatitis B vaccine to very low birth weight (VLBW infants at 30 days of chronologic age usually is not practical, because most VLBW infants are not medically stable at that age. We use an alternative body-weight-based protocol, and evaluate its efficacy in an endemic area under a universal immunization program. METHODS: The immunogenicity of the current hepatitis B vaccination strategy in 155 VLBW preterm infants was evaluated at age 2 to 13 years, with parental consent. All of the infants were born between 1995 and 2006, and received their first dose of hepatitis B vaccine when they reached 2,000-2,200 g, irrespective of chronological age. Hepatitis B immunoglobulin (HBIG was given at birth to infants born to HBsAg(+/HBeAg(+ mothers. RESULTS: All 155 of the recruited children were HBsAg and anti-HBc negative. The anti-HBs seropositivity rate (geometric mean titer was 84.1% (146.5 mIU/mL for children under 3 years, 73.5% (68.8 mIU/mL for 4- to 7-year-olds, 27.7% (55.4 mIU/mL for 8- to 11-year-olds and 20% (6.0 mIU/mL for children ≥12 years of age. More than 90% of these children received the first vaccination after 30 days of age, half (51% at 60 to 90 days, and 29 children (18.6% after 90 days of age. Of the 26 infants born to HBsAg(+ mothers, 6/6 infants of HBeAg(+ mothers received HBIG at birth, and 12/20 infants of HBeAg(- mothers received HBIG. None of the 26 infants became infected. CONCLUSIONS: Delaying hepatitis B vaccinations in VLBW preterm infants until they reach a weight of 2,000 g, with the administration of HBIG at birth for infants of HBsAg(+ mothers provided adequate immunogenicity and protection in a highly endemic area. Weight-based policy of hepatitis B vaccination is an effective and practical alternative strategy for VLBW infants.

  10. Efficacy and safety of fixed-dose combination therapy with olmesartan medoxomil and rosuvastatin in Korean patients with mild to moderate hypertension and dyslipidemia: an 8-week, multicenter, randomized, double-blind, factorial-design study (OLSTA-D RCT: OLmesartan rosuvaSTAtin from Daewoong

    Directory of Open Access Journals (Sweden)

    Park JS

    2016-08-01

    Full Text Available Jin-Sun Park,1,* Joon-Han Shin,1,* Taek-Jong Hong,2 Hong-Seog Seo,3 Wan-Joo Shim,4 Sang-Hong Baek,5 Jin-Ok Jeong,6 Youngkeun Ahn,7 Woong-Chol Kang,8 Young-Hak Kim,9 Sang-Hyun Kim,10 Min-Su Hyon,11 Dong-Hoon Choi,12 Chang-Wook Nam,13 Tae-Ho Park,14 Sang-Chol Lee,15 Hyo-Soo Kim16 1Department of Cardiology, Ajou University School of Medicine, Suwon, 2Division of Cardiology, Pusan National University Hospital, Busan, 3Division of Cardiology, Korea University Guro Hospital, Korea University College of Medicine, 4Division of Cardiology, Korea University Anam Hospital, 5Cardiovascular Division, Catholic University of Korea, Seoul St Mary’s Hospital, Seoul, 6Division of Cardiology, Chungnam National University Hospital, Daejeon, 7Division of Cardiology, Chonnam National University Hospital, Gwangju, 8Division of Cardiology, Gachon University Gil Hospital, Incheon, 9Division of Cardiology, Asan Medical Center, College of Medicine, University of Ulsan, 10Division of Cardiology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, 11Division of Cardiology, Soonchunhyang University Hospital, 12Division of Cardiology, Yonsei University Severance Hospital, Seoul, 13Department of Internal Medicine, Keimyung University Dongsan Medical Center, Daegu, 14Division of Cardiology, Dong-A University Hospital, Busan, 15Cardiovascular Imaging Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, 16Department of Internal Medicine, Cardiovascular Center, Seoul National University Hospital, Seoul, Korea *These authors contributed equally to this work Abstract: The pill burden of patients with hypertension and dyslipidemia can result in poor medication compliance. This study aimed to evaluate the efficacy and safety of fixed-dose combination (FDC therapy with olmesartan medoxomil (40 mg and rosuvastatin (20 mg in Korean patients with mild to moderate hypertension and dyslipidemia. This multicenter, randomized, double

  11. 吉西他滨固定剂量率输注联合多西他赛治疗复发难治性软组织肉瘤的疗效与安全性%Efficacy and safety of fixed dose rate gemcitabine infusion in combination with docetaxel in patients with relapsed/refractory soft tissue sarcoma

    Institute of Scientific and Technical Information of China (English)

    姚志华; 杨树军; 赵燕; 姚书娜; 郭宏强; 刘艳艳

    2014-01-01

    Objective To evaluate the efficacy and safety of fixed dose rate (FDR) gemcitabine infusion in combination with docetaxel in patients with relapsed/refractory soft tissue sarcoma.Methods Clinicopathological data of 28 patients with relapsed/refractory soft tissue sarcoma treated in our hospital from April 2008 to August 2013 were reviewed in this study.The patients received 900 mg/m2 gemcitabine with a FDR infusion (10 mg/m2/min) in a total dose of 900 mg/m2 on days 1 and 8,and 75 mg/m2 docetaxel intravenously over 60 min on day 8 of a 21-day cycle.When irradiation was conducted before drug therapy,the dose of gemcitabine was reduced to 675 mg/m2 on days 1 and 8.The clinicopathological characteristics,short-term response,long-term survival status and toxicity were analyzed retrospectively.Results The 28 patients received a total of 118 cycles of therapy (range 1-8 cycles,median 4 cycles per patient).No patient achieved complete response (CR),4 partial responses (PR) and 11 stable diseases (SD),with an overall response rate (ORR) of 14.3% and clinical benefit rate (CBR) of 53.6%.The median progression-free survival (PFS) was 3.2 months and the median overall survival (OS) was 8.5 months.PFS and OS were correlated with the response to this treatment regimen (P < 0.0001).Patients with clinical benefit had significantly better PFS and OS than the patients with progressive disease (P < 0.05 for all).The ORR,CBR,PFS and OS were better in patients with leiomyosarcoma than in patients with other histological subtypes in this study,but the differences were not significant (P > 0.05 for all).Grade 3-4 neutropenia,anemia and thrombocytopenia were 50.0%,17.9% and 14.3%,respectively.Only one patient (3.6%)had febrile neutropenia.Grade 3 non-hematologic toxicities were nausea/vomiting (3.6%) and mucositis (3.6%).No grade 4 non-hematologic toxicities were observed.Almost all non-hematologic toxicities were grade 1-2 and manageable.Conclusions The fixed dose

  12. Differences between ceryical cancer radical radiotherapy dose intensity modulated rotary positiye displacement technology and dynamic fixed field IMRT technology%宫颈癌根治性放疗旋转容积调强技术及固定野动态调强放疗技术的剂量学差异

    Institute of Scientific and Technical Information of China (English)

    徐洋; 刘东丽; 张佩娟; 齐华; 陈菁

    2016-01-01

    Objectiye To analysis the metrology differences of cervical cancer radical radiotherapy IMRT technology transfer volume (VMAT)and the fixed field IMRT dynamic technology(9 - IMRT)and compare the threaten to the organs at risk and the accelerator hops. Methods 15 cases of cervical cancer author Radiology radical radiotherapy on CT images with a 2 and 9 arc VMAAT field IMRT plan were col-lected. Target volume dose differences,target dose conformal and uniform organ dosimetry differences in degree of the two radiotherapy planning were compared. The threaten to the organs at risk and the accelerator hops between the two groups were compared. Results Compared with 9 -IMRT,VMAT dose distribution uniformity(HI)and conformal(CI)was more preferably( P 0. 05). The average number of machine hop between VMAT plan(756. 85 ± 134. 62)and 9 - IM-RT plan(1 104. 12 ± 186. 97)had significant difference( P < 0. 05). Conclusion ①VMRI and 9 - IMRT planning target volume dose can meet metrological requirements. ②VMAT planning target volume dose conformal degree and uniformity is better than the 9 - IMRT. ③VMAT can reduce the dose of organs at risk,lower the number of machine hop. Therefore,it can provide better treatment and has a better organ protection.%目的:对比分析宫颈癌根治性放疗中旋转容积调强技术( VMAT)与固定野动态调强技术(9- IMRT)计量学差异,以及危及的器官剂量学差异和加速器跳数。方法选取放射科行根治性放疗的宫颈癌患者15例,对同个 CT图像进行2弧 VMAT 以及9野 IMRT 计划,对比两种放疗计划靶区剂量差异、靶区剂量适形度及均匀度,对比两种方法危及的器官剂量学差异、加速器跳数。结果 与 9- IMRT 相比,VMAT 的剂量分布均匀度(HI)及适形度(CI)更优( P<0.05)。股骨头 VMAT 的 V20 较 9- IMRT 低;直肠 VMAT 计划的直肠接受30 Gy 剂量较9野计划低;膀胱 VMAT 计划膀胱 V30明显低于 9- IMRT

  13. Vancomycin Utilization Evaluation: Are We Dosing Appropriately?

    Directory of Open Access Journals (Sweden)

    Ladan Ayazkhoo

    2015-10-01

    Full Text Available Background: Inappropriate use of vancomycin not only increase health care costs but also contribute to the emergence of resistant organisms. Higher trough serum vancomycin concentrations (>10mg/L has been recommended for avoidance of development of resistance. We aim to compare the administered dose with recommended doses based on guideline-recommended weight-based dosing.Methods: In a cross sectional study, all patients who received vancomycin between July and October 2013, in infectious disease, internal medicine wards and emergency department of a teaching hospital in Tehran, Iran were entered to the study. Indication of vancomycin and necessary data for dose calculation including height and serum creatinine were recorded. Prescribed doses were compared with recommended doses in guidelines and calculated Glomerular filtration rate (GFR for each patient.Results: One hundred and four patients (45 females and 59 males recruited in the study. Our results indicated that, from all administered doses of vancomycin, 64.4% and 88.8% differs significantly (more than 20% based on American Pharmacist Association (AphA vancomycin monograph and guideline-recommended, weight-based vancomycin dosing (for adults, respectively.Conclusion: Underdosing of vancomycin is a major risk factor for developing resistance of gram positive organisms to this glycopeptide. Our results showed that more than half of patients receiving vancomycin are in the risk of low drug levels based on guidelines. So, having a comprehensive plan for the proper use of this drug especially designing effective internal guidelines can prevent emergence of resistance to vancomycin in future.

  14. Inadequacy of Body Weight-Based Recommendations for Individual Protein Intake—Lessons from Body Composition Analysis

    OpenAIRE

    Corinna Geisler; Prado, Carla M.; Müller, Manfred J.

    2016-01-01

    Current body weight-based protein recommendations are ignoring the large variability in body composition, particularly lean mass (LM), which drives protein requirements. We explored and highlighted the inter-individual variability of weight versus body composition-adjusted protein intakes by secondary analysis in three cohorts of (1) 574 healthy adults (mean ± SD age: 41.4 ± 15.2 years); (2) 403 cirrhotic patients (age: 44.7 ± 12.3 years) and (3) 547 patients with lung cancer (age: 61.3 ± 8.2...

  15. Application of U-fixed red wax mask in radiotherapy

    Institute of Scientific and Technical Information of China (English)

    Kejia Liu; Jing Song; Rui Song; Zhiyong Liu; Gang Ni; Wei Ge

    2014-01-01

    Objective:The aim of our study was to compared non-red wax compensator and adding red wax compensator in the treatment plans of the minimum dose, maximum dose, mean dose and target surface dose, and compare the dose volume histograms (DVH) parameters and isodose distributions of two plans. Methods:From January 2009 to December 2010, 8 patients with superficial head and neck cancer and without surgery treatment were col ected. They al confirmed by cancer center, Tianmen First People’s Hospital. Topslane WiMRT was used to design the treatment plan of non-red wax compensa-tor and adding red wax compensator, with 6 MV photons using three-dimensional conformal irradiation mode design, the prescription dose was 50 Gy/25 times. Results:Compared non-red wax compensator with adding red wax compensator, its target minimum dose (t=-3.157, P0.05) and mean dose (t=-9.914, P>0.05) were considered no significant dif erence. Conclusion:The use of U-shaped mask fixed red wax film production in conformal radiotherapy tissue compensator can significantly improve the surface dose and dose distribution superficial planning target volume.

  16. National Radiological Fixed Lab Data

    Data.gov (United States)

    U.S. Environmental Protection Agency — The National Radiological Fixed Laboratory Data Asset includes data produced in support of various clients such as other EPA offices, EPA Regional programs, DOE,...

  17. Elevated Fixed Platform Test Facility

    Data.gov (United States)

    Federal Laboratory Consortium — The Elevated Fixed Platform (EFP) is a helicopter recovery test facility located at Lakehurst, NJ. It consists of a 60 by 85 foot steel and concrete deck built atop...

  18. Fixed Exchange Rates and Trade

    OpenAIRE

    Michael W. Klein; Jay C. Shambaugh

    2004-01-01

    A classic argument for a fixed exchange rate is its promotion of trade. Empirical support for this, however, is mixed. While one branch of research consistently shows a small negative effect of exchange rate volatility on trade, another, more recent, branch presents evidence of a large positive impact of currency unions on trade. This paper helps resolve this disconnect. Our results, which use a new data-based classification of fixed exchange rate regimes, show a large, significant effect of ...

  19. The paradoxical moderating effect of body image investment on the impact of weight-based derogatory media.

    Science.gov (United States)

    Boersma, Katelyn E; Jarry, Josée L

    2013-03-01

    Weight-based derogatory media consist of derogation of celebrities for failing to meet the thin ideal. This study examined the impact of weight-based derogatory media on women's body satisfaction, appearance self-esteem, fear of negative appearance evaluation, and negative affect. Female undergraduates (N=240) were exposed to either tabloid-style pictures and articles derogating average size celebrities for gaining weight, or to the same images accompanied by neutral information. Women in the derogation condition reported greater fear of negative appearance evaluation than did women in the neutral media condition. Contrary to predictions, women low in maladaptive body image investment reported lower body satisfaction and appearance self-esteem in the derogatory media condition than they did in the neutral condition, while women high in maladaptive investment did not differ across conditions. Highly invested women's unexpected reaction may be understood as a defence against a threat to a valued domain of the self. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Inadequacy of Body Weight-Based Recommendations for Individual Protein Intake-Lessons from Body Composition Analysis.

    Science.gov (United States)

    Geisler, Corinna; Prado, Carla M; Müller, Manfred J

    2016-12-31

    Current body weight-based protein recommendations are ignoring the large variability in body composition, particularly lean mass (LM), which drives protein requirements. We explored and highlighted the inter-individual variability of weight versus body composition-adjusted protein intakes by secondary analysis in three cohorts of (1) 574 healthy adults (mean ± SD age: 41.4 ± 15.2 years); (2) 403 cirrhotic patients (age: 44.7 ± 12.3 years) and (3) 547 patients with lung cancer (age: 61.3 ± 8.2 years). LM was assessed using different devices (magnetic resonance imaging, dual-energy X-ray absorptiometry, computer tomography, total body potassium and bioelectrical impedance), body weight-based protein intake, its ratio (per kg LM) and mean protein requirement were calculated. Variability in protein intake in all cohorts ranged from 0.83 to 1.77 g protein per kg LM per day using (theoretical protein intake of 60 g protein per day). Calculated mean protein requirement was 1.63 g protein per kg LM per day; consequently, 95.3% of healthy subjects, 100% of cirrhotic and 97.4% of cancer patients would present with a low protein intake per kg LM. Weight-adjusted recommendations are inadequate to address the LM specific differences in protein needs of healthy subjects or clinical populations. Absolute protein intake seems to be more relevant compared to the relative proportion of protein, which in turn changes with different energy needs.

  1. Inadequacy of Body Weight-Based Recommendations for Individual Protein Intake—Lessons from Body Composition Analysis

    Directory of Open Access Journals (Sweden)

    Corinna Geisler

    2016-12-01

    Full Text Available Current body weight-based protein recommendations are ignoring the large variability in body composition, particularly lean mass (LM, which drives protein requirements. We explored and highlighted the inter-individual variability of weight versus body composition-adjusted protein intakes by secondary analysis in three cohorts of (1 574 healthy adults (mean ± SD age: 41.4 ± 15.2 years; (2 403 cirrhotic patients (age: 44.7 ± 12.3 years and (3 547 patients with lung cancer (age: 61.3 ± 8.2 years. LM was assessed using different devices (magnetic resonance imaging, dual-energy X-ray absorptiometry, computer tomography, total body potassium and bioelectrical impedance, body weight-based protein intake, its ratio (per kg LM and mean protein requirement were calculated. Variability in protein intake in all cohorts ranged from 0.83 to 1.77 g protein per kg LM per day using (theoretical protein intake of 60 g protein per day. Calculated mean protein requirement was 1.63 g protein per kg LM per day; consequently, 95.3% of healthy subjects, 100% of cirrhotic and 97.4% of cancer patients would present with a low protein intake per kg LM. Weight-adjusted recommendations are inadequate to address the LM specific differences in protein needs of healthy subjects or clinical populations. Absolute protein intake seems to be more relevant compared to the relative proportion of protein, which in turn changes with different energy needs.

  2. Inadequacy of Body Weight-Based Recommendations for Individual Protein Intake—Lessons from Body Composition Analysis

    Science.gov (United States)

    Geisler, Corinna; Prado, Carla M.; Müller, Manfred J.

    2016-01-01

    Current body weight-based protein recommendations are ignoring the large variability in body composition, particularly lean mass (LM), which drives protein requirements. We explored and highlighted the inter-individual variability of weight versus body composition-adjusted protein intakes by secondary analysis in three cohorts of (1) 574 healthy adults (mean ± SD age: 41.4 ± 15.2 years); (2) 403 cirrhotic patients (age: 44.7 ± 12.3 years) and (3) 547 patients with lung cancer (age: 61.3 ± 8.2 years). LM was assessed using different devices (magnetic resonance imaging, dual-energy X-ray absorptiometry, computer tomography, total body potassium and bioelectrical impedance), body weight-based protein intake, its ratio (per kg LM) and mean protein requirement were calculated. Variability in protein intake in all cohorts ranged from 0.83 to 1.77 g protein per kg LM per day using (theoretical protein intake of 60 g protein per day). Calculated mean protein requirement was 1.63 g protein per kg LM per day; consequently, 95.3% of healthy subjects, 100% of cirrhotic and 97.4% of cancer patients would present with a low protein intake per kg LM. Weight-adjusted recommendations are inadequate to address the LM specific differences in protein needs of healthy subjects or clinical populations. Absolute protein intake seems to be more relevant compared to the relative proportion of protein, which in turn changes with different energy needs. PMID:28042853

  3. Efficacy and safety of repaglinide/metformin fixed-dose combination tablet in the treatment of type 2 diabetic patients%瑞格列奈盐酸二甲双胍复方片治疗2型糖尿病的有效性及安全性研究

    Institute of Scientific and Technical Information of China (English)

    王昕; 陈秋; 吕肖锋; 叶山东; 姜兆顺; 倪海祥; 王文汇; 李凯利; 汤旭磊

    2014-01-01

    目的 以联合使用瑞格列奈片和盐酸二甲双胍片为阳性对照,评价瑞格列奈盐酸二甲双胍复方片治疗中国2型糖尿病患者的有效性和安全性.方法 采用多中心、随机、双肓三模拟、阳性药物平行对照,非劣效性试验设计方案.入选的受试者为18 ~ 75岁,病程至少3个月,在单药治疗下HbA1C>7.0%的2型糖尿病患者,筛选后按1∶1的比例随机进入试验组或对照组,分别接受瑞格列奈盐酸二甲双胍复方片(1 mg/500 mg)或联合使用瑞格列奈片(1 mg)和盐酸二甲双胍片(500 mg)治疗,治疗期为14周.结果 292例受试者进行随机化,255例完成试验.两组基线资料的差异无统计学意义.治疗14周后复方片组和联合用药组HbA1C分别下降(1.40±1.15)%和(1.23±1.00)%,两组变化值均数之差的双侧95%可信区间的上限0.08小于非劣效临床界值,因此非劣效性结论成立.复方片组和联合用药组经治疗后HbA1C<7.0%的百分比分别为55.86%和54.17%,两组间的差异无统计学意义(P>0.05).两组间的不良事件和低血糖的差异无统计学意义(P>0.05).结论 瑞格列奈盐酸二甲双胍复方片在治疗2型糖尿病患者中具有不劣于目前常用的瑞格列奈片联合盐酸二甲双胍片的临床疗效,且不良事件和不良反应发生情况相似.复方制剂服用相对方便,提高患者服药的依从性,从而改善长期血糖控制.%Objective To compare the safety and efficacy of repaglinide/metformin fixed-dose combination (FDC) tablet versus repaglinide and metformin as separate tablets in Chinese subjects with type 2 diabetes.Methods A multicenter,randomized,blind,eontrolled,parallel-group,non-inferiority trial was carried out.Eligible subjects (18-75 years oll) had type 2 diabetes for more than 3 months,HbA1C > 7.0% under single oral antidiabetes agents.Subjects were randomized (1 ∶ 1) to repaglinide/metformin fixed-dose combination tablet (1 mg/500

  4. A Comparison Simulation of Fixed-fixed Type MEMS Switches

    Science.gov (United States)

    Rezazadeh, G.; Sadeghian, H.; Malekpour, E.

    2006-04-01

    In the present work pull-in voltage of fixed-fixed end type MEMS switches with variative electrostatic area has been calculated using a distributed model and applying a full nonlinear finite difference discretizing method. The governing nonlinear differential equation has been derived using of the variational principle for multi domain electromechanical coupled system. The numerical results of the beam with variative electrostatic area with the results of Coupled-Domain Finite Element method have been compared and very good agreement has been achieved.

  5. Diclofenac Induced Fixed Drug Eruption

    Directory of Open Access Journals (Sweden)

    Dr. Umeshchandra C Honnaddi

    2016-02-01

    Full Text Available Background: Diclofenac is the most commonly used non-steroidal anti-inflammatory drug (NSAID for treating various inflammatory and painful conditions. It is generally well tolerated; gastric upset is the most common adverse effect. However very few cases of fixed drug eruptions were reported. Here we present a case of Diclofenac Induced Fixed Drug Eruption. A 62 year old male patient developed fixed drug eruptions with plaques on left thigh two days after receiving diclofenac for osteoarthritic pain. Other etiologies including insect bite, infections were ruled out. One week later after stopping the drug, the lesions were subsided. Diclofenac was strongly suspected as the casual drug. CD8+ effector T-cells have shown to play an important role. However it seems to be a reversible and drug related event. Although it is not life-threatening, fixed drug eruption can have significant effect on the quality of life of patients.Conclusion: Diclofenac is one of the most commonly prescribed NSAIDs by the Physicians. It is usually well tolerated, gastric upset is the most common adverse effect noted with this drug. This case is being reported to highlight a drug as safe as Diclofenac may also be associated with Fixed Drug Eruptions.

  6. Evidence of the Big Fix

    CERN Document Server

    Hamada, Yuta; Kawana, Kiyoharu

    2014-01-01

    We give an evidence of the Big Fix. The theory of wormholes and multiverse suggests that the parameters of the Standard Model are fixed in such a way that the total entropy at the late stage of the universe is maximized, which we call the maximum entropy principle. In this paper, we discuss how it can be confirmed by the experimental data, and we show that it is indeed true for the Higgs vacuum expectation value $v_{h}$. We assume that the baryon number is produced by the sphaleron process, and that the current quark masses, the gauge couplings and the Higgs self coupling are fixed when we vary $v_{h}$. It turns out that the existence of the atomic nuclei plays a crucial role to maximize the entropy. This is reminiscent of the anthropic principle, however it is required by the fundamental low in our case.

  7. Evidence of the big fix

    Science.gov (United States)

    Hamada, Yuta; Kawai, Hikaru; Kawana, Kiyoharu

    2014-06-01

    We give an evidence of the Big Fix. The theory of wormholes and multiverse suggests that the parameters of the Standard Model are fixed in such a way that the total entropy at the late stage of the universe is maximized, which we call the maximum entropy principle. In this paper, we discuss how it can be confirmed by the experimental data, and we show that it is indeed true for the Higgs vacuum expectation value vh. We assume that the baryon number is produced by the sphaleron process, and that the current quark masses, the gauge couplings and the Higgs self-coupling are fixed when we vary vh. It turns out that the existence of the atomic nuclei plays a crucial role to maximize the entropy. This is reminiscent of the anthropic principle, however it is required by the fundamental law in our case.

  8. Fixed-point signal processing

    CERN Document Server

    Padgett, Wayne T

    2009-01-01

    This book is intended to fill the gap between the ""ideal precision"" digital signal processing (DSP) that is widely taught, and the limited precision implementation skills that are commonly required in fixed-point processors and field programmable gate arrays (FPGAs). These skills are often neglected at the university level, particularly for undergraduates. We have attempted to create a resource both for a DSP elective course and for the practicing engineer with a need to understand fixed-point implementation. Although we assume a background in DSP, Chapter 2 contains a review of basic theory

  9. Perfect and Imperfect Gauge Fixing

    CERN Document Server

    Shirzad, A

    2006-01-01

    Gauge fixing may be done in different ways. We show that using the chain structure to describe a constrained system, enables us to use either a perfect gauge, in which all gauged degrees of freedom are determined; or an imperfect gauge, in which some first class constraints remain as subsidiary conditions to be imposed on the solutions of the equations of motion. We also show that the number of constants of motion depends on the level in a constraint chain in which the gauge fixing condition is imposed. The relativistic point particle, electromagnetism and the Polyakov string are discussed as examples and perfect or imperfect gauges are distinguished.

  10. Fixed effects analysis of variance

    CERN Document Server

    Fisher, Lloyd; Birnbaum, Z W; Lukacs, E

    1978-01-01

    Fixed Effects Analysis of Variance covers the mathematical theory of the fixed effects analysis of variance. The book discusses the theoretical ideas and some applications of the analysis of variance. The text then describes topics such as the t-test; two-sample t-test; the k-sample comparison of means (one-way analysis of variance); the balanced two-way factorial design without interaction; estimation and factorial designs; and the Latin square. Confidence sets, simultaneous confidence intervals, and multiple comparisons; orthogonal and nonorthologonal designs; and multiple regression analysi

  11. Methotrexate Dosing Regimen for Plaque-type Psoriasis: A Systematic Review of the Use of Test-dose, Start-dose, Dosing Scheme, Dose Adjustments, Maximum Dose and Folic Acid Supplementation.

    Science.gov (United States)

    Menting, Stef P; Dekker, Paul M; Limpens, Jacqueline; Hooft, Lotty; Spuls, Phyllis I

    2016-01-01

    There is a range of methotrexate dosing regimens for psoriasis. This review summarizes the evidence for test-dose, start-dose, dosing scheme, dose adjustments, maximum dose and use of folic acid. A literature search for randomized controlled trials and guidelines was performed. Twenty-three randomized controlled trials (29 treatment groups) and 10 guidelines were included. Two treatment groups used a test-dose, 5 guidelines recommend it. The methotrexate start-dose in randomized controlled trials varied from 5 to 25 mg/week, most commonly being either 7.5 mg or 15 mg. Guidelines vary from 5 to 15 mg/week. Methotrexate was administered as a single dose or in a Weinstein schedule in 15 and 11 treatment-groups, respectively; both recommended equally in guidelines. A fixed dose (n = 18), predefined dose (n = 3), or dose adjusted on clinical improvement (n = 8) was used, the last also being recommended in guidelines. Ten treatment groups used folic acid; in 2 it was allowed, in 14 not mentioned, and in 3 no folic acid was used. Most guidelines recommend the use of folic acid. Authors' suggestions for methotrexate dosing are given.

  12. Flat coalgebraic fixed point logics

    CERN Document Server

    Schröder, Lutz

    2010-01-01

    Fixed point logics have a wide range of applications in computer science, in particular in artificial intelligence and concurrency. The most expressive logics of this type are the mu-calculus and its relatives. However, popular fixed point logics tend to trade expressivity for simplicity and readability, and in fact often live within the single variable fragment of the mu-calculus. The family of such flat fixed point logics includes, e.g., CTL, the *-nesting-free fragment of PDL, and the logic of common knowledge. Here, we extend this notion to the generic semantic framework of coalgebraic logic, thus covering a wide range of logics beyond the standard mu-calculus including, e.g., flat fragments of the graded mu-calculus and the alternating-time mu-calculus (such as ATL), as well as probabilistic and monotone fixed point logics. Our main results are completeness of the Kozen-Park axiomatization and a timed-out tableaux method that matches EXPTIME upper bounds inherited from the coalgebraic mu-calculus but avo...

  13. Landau Gauge Fixing on GPUs

    CERN Document Server

    Cardoso, Nuno; Bicudo, Pedro; Oliveira, Orlando

    2012-01-01

    In this paper we present and explore the performance of Landau gauge fixing in GPUs using CUDA. We consider the steepest descent algorithm with Fourier acceleration, and compare the GPU performance with a parallel CPU implementation. Using $32^4$ lattice volumes, we find that the computational power of a single Tesla C2070 GPU is equivalent to approximately 256 CPU cores.

  14. Fixed drug eruption to tartrazine.

    Science.gov (United States)

    Orchard, D C; Varigos, G A

    1997-11-01

    An 11-year-old girl with a recurrent fixed drug eruption to tartrazine on the dorsum of the left hand is presented. Oral provocation tests to both the suspected food, an artificially coloured cheese crisp, and to tartrazine were positive. This case highlights fire need to consider artificial flavours, colours and preservatives as potential culprits in classic drug eruptions.

  15. Analysis on the effect of fixed-dose combination in the initial treatment for patients with smear-positive pulmonary tuberculosis%固定剂量复合剂治疗初治涂阳肺结核效果分析

    Institute of Scientific and Technical Information of China (English)

    聂志学; 应潜; 汪仕文; 赖建萍; 陈小菁; 王坚; 王自扬

    2012-01-01

    目的 评价国产抗结核固定剂量复合剂(FDC)的临床效果、安全性和可行性.方法 将184例初治涂阳肺结棱患者分为研究组(FDC)和对照组(组合药),并进行临床应用对比分析研究.结果 研究组与对照组:治愈率分别为96.7%、89.1%,停药率为2.2%、9.8%(均P<0.05);治疗依从性在药物接受程度、服药感受和方式方面,研究组均优于对照组(前两者P<0.01,后者P< 0.05);痰检转阴率、X线胸片改变率和不良反应发生率两组差异均P>0.05.药品总用量FDC比组合药在强化期减少42.14%,继续期却增加86.96%.治愈1例病人平均成本FDC比组合药增加99.7%.结论 FDC在治愈率、停药率和治疗依从性以及减少耐药方面比组合药更显优势,可以在国内推广应用,但也需要做一些改进.%OBJECTIVE To evaluate the clinical effect, security and feasibility of domestic fixed-dose combination (FDC) in tuberculosis treatment. METHODS 184 examples of initial smear-positive pulmonary tuberculosis patients were assigned to the case group by using FDC and the control group by using the blister pack. We used comparative analysis for the clinical application. RESULTS Compared with he case group and the control group, the cure rate respectively was 96.7% and 89.1%, respectively; The stopped treatment rate was 2.2% and 9.8% , respectively, (both were P 0.05). Using FDC was reduced by 42.14% than that of the combination drug in the intensive phase, but increased by 86.96% in the consolidation period. The average cost of FDC for curing one patient was significantly increased by 99.7%. CONCLUSION FDC has obvious advantage in cure rate, stopped treatment rate, patient's compliance and reducing tuberculosis patients of drug resistance. FDC may be promoted and applied in the domestic, but it needs to be done some improvement.

  16. Adhesives for fixed orthodontic bands.

    Science.gov (United States)

    Millett, Declan T; Glenny, Anne-Marie; Mattick, Rye Cr; Hickman, Joy; Mandall, Nicky A

    2016-10-25

    Orthodontic treatment involves using fixed or removable appliances (dental braces) to correct the positions of teeth. It has been shown that the quality of treatment result obtained with fixed appliances is much better than with removable appliances. Fixed appliances are, therefore, favoured by most orthodontists for treatment. The success of a fixed orthodontic appliance depends on the metal attachments (brackets and bands) being attached securely to the teeth so that they do not become loose during treatment. Brackets are usually attached to the front and side teeth, whereas bands (metal rings that go round the teeth) are more commonly used on the back teeth (molars). A number of adhesives are available to attach bands to teeth and it is important to understand which group of adhesives bond most reliably, as well as reducing or preventing dental decay during the treatment period. To evaluate the effectiveness of the adhesives used to attach bands to teeth during fixed appliance treatment, in terms of:(1) how often the bands come off during treatment; and(2) whether they protect the banded teeth against decay during fixed appliance treatment. The following electronic databases were searched: Cochrane Oral Health's Trials Register (searched 2 June 2016), Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 5) in the Cochrane Library (searched 2 June 2016), MEDLINE Ovid (1946 to 2 June 2016) and EMBASE Ovid (1980 to 2 June 2016). We searched ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. Randomised and controlled clinical trials (RCTs and CCTs) (including split-mouth studies) of adhesives used to attach orthodontic bands to molar teeth were selected. Patients with full arch fixed orthodontic appliance(s) who had bands attached to molars were included. All review authors

  17. Can mushrooms fix atmospheric nitrogen?

    Indian Academy of Sciences (India)

    H S Jayasinghearachchi; Gamini Seneviratne

    2004-09-01

    It is generally reported that fungi like Pleurotus spp. can fix nitrogen (N2). The way they do it is still not clear. The present study hypothesized that only associations of fungi and diazotrophs can fix N2. This was tested in vitro. Pleurotus ostreatus was inoculated with a bradyrhizobial strain nodulating soybean and P. ostreatus with no inoculation was maintained as a control. At maximum mycelial colonization by the bradyrhizobial strain and biofilm formation, the cultures were subjected to acetylene reduction assay (ARA). Another set of the cultures was evaluated for growth and nitrogen accumulation. Nitrogenase activity was present in the biofilm, but not when the fungus or the bradyrhizobial strain was alone. A significant reduction in mycelial dry weight and a significant increase in nitrogen concentration were observed in the inoculated cultures compared to the controls. The mycelial weight reduction could be attributed to C transfer from the fungus to the bradyrhizobial strain, because of high C cost of biological N2 fixation. This needs further investigations using 14C isotopic tracers. It is clear from the present study that mushrooms alone cannot fix atmospheric N2. But when they are in association with diazotrophs, nitrogenase activity is detected because of the diazotrophic N2 fixation. It is not the fungus that fixes N2 as reported earlier. Effective N2 fixing systems, such as the present one, may be used to increase protein content of mushrooms. Our study has implications for future identification of as yet unidentified N2 systems occurring in the environment.

  18. Efficacy and safety of two fixed-dose combinations of S-amlodipine and telmisartan (CKD-828 versus S-amlodipine monotherapy in patients with hypertension inadequately controlled using S-amlodipine monotherapy: an 8-week, multicenter, randomized, double-blind, Phase III clinical study

    Directory of Open Access Journals (Sweden)

    Ihm SH

    2016-11-01

    Full Text Available Sang-Hyun Ihm,1 Hui-Kyung Jeon,1 Tae-Joon Cha,2 Taek-Jong Hong,3 Sang-Hyun Kim,4 Nae-Hee Lee,5 Jung Han Yoon,6 Namsik Yoon,7 Kyung-Kuk Hwang,8 Sang-Ho Jo,9 Ho-Joong Youn1 1Division of Cardiology, Department of Internal Medicine, The Catholic University of Korea, Seoul, 2Division of Cardiology, Department of Internal Medicine, Kosin University College of Medicine, 3Division of Cardiology, Department of Internal Medicine, Pusan National University Hospital, Busan, 4Division of Cardiology, Department of Internal Medicine, Boramae Medical Center, Seoul National University College of Medicine, Seoul, 5Department of Cardiology, Soonchunhyang University Hospital, Bucheon, 6Division of Cardiology, Wonju College of Medicine, Yonsei University, Wonju, 7Department of Cardiology, Chonnam National University Hospital, Gwangju, 8Department of Internal Medicine, Chungbuk National University, College of Medicine, Cheongju, 9Division of Cardiology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, South Korea Purpose: To evaluate the blood pressure (BP lowering efficacy and safety of CKD-828, a fixed-dose combination of S-amlodipine (the more active isomer of amlodipine besylate, which is calcium channel blocker and telmisartan (long acting angiotensin receptor blocker, in patients with hypertension inadequately controlled with S-amlodipine monotherapy.Patients and methods: Eligible patients (N=187 who failed to respond after 4-week S-amlodipine 2.5 mg monotherapy (sitting diastolic blood pressure [sitDBP] ≥90 mmHg to receive CKD-828 2.5/40 mg (n=63, CKD-828 2.5/80 mg (n=63, or S-amlodipine 2.5 mg (n=61 for 8 weeks. The primary efficacy endpoint, mean sitDBP change from baseline to Week 8, was compared between the combination (CKD-828 2.5/40 mg and CKD-828 2.5/80 mg and S-amlodipine monotherapy groups. The safety was assessed based on adverse events, vital signs, and physical examination findings.Results: After the 8

  19. On Fixing number of Functigraphs

    OpenAIRE

    Fazil, Muhammad; Javaid, Imran; Murtaza, Muhammad

    2016-01-01

    The fixing number of a graph $G$ is the order of the smallest subset $S$ of its vertex set $V(G)$ such that stabilizer of $S$ in $G$, $\\Gamma_{S}(G)$ is trivial. Let $G_{1}$ and $G_{2}$ be disjoint copies of a graph $G$, and let $g:V(G_{1})\\rightarrow V(G_{2})$ be a function. A functigraph $F_{G}$ consists of the vertex set $V(G_{1})\\cup V(G_{2})$ and the edge set $E(G_{1})\\cup E(G_{2})\\cup \\{uv:v=g(u)\\}$. In this paper, we study the behavior of the fixing number in passing from $G$ to $F_{G}...

  20. Oral rehabilitation with fixed prosthesis

    OpenAIRE

    Watanabe Velásquez, Romel; Dpto. Académico Estomatología Rehabilitadora. Facultad Odontología. UNMSM. Lima, Perú.; Salcedo Moncada, Doris; Dpto. Académico Estomatología Rehabilitadora. Facultad Odontología. UNMSM. Lima, Perú.; Ochoa Tataje, Julio; Dpto. Académico Estomatología Rehabilitadora. Facultad Odontología. UNMSM. Lima, Perú; Horna Palomino, Hernán; Dpto. Académico Estomatología Rehabilitadora. Facultad Odontología. UNMSM. Lima, Perú.; Herrera Cisneros, Marco; Dpto. Académico Estomatología Rehabilitadora. Facultad Odontología. UNMSM. Lima, Perú.; Paz Fernández, Juan José; Dpto. Académico Estomatología Rehabilitadora. Facultad Odontología. UNMSM. Lima, Perú.

    2014-01-01

    This treatment was carried out in a 58 years old male patient, who has had the antecedent of a car crash accident two years before; he loosed several teeth and fractured others. Pulp necrosis and alteration of occlusal plane occurred. Because of the pathologies presented, it was installed a multidisciplinary treatment phase having periodontal, endodontic, surgical and orthodontic procedures, tehe installation of posts, crowns and fixed bridges. Treatment was carried out for five months. El...

  1. Zirconia in fixed implant prosthodontics.

    Science.gov (United States)

    Guess, Petra Christine; Att, Wael; Strub, Joerg Rudolf

    2012-10-01

    CAD/CAM technology in combination with zirconia ceramic has increasingly gained popularity in implant dentistry. This narrative review presents the current knowledge on zirconia utilized as framework material for implant-borne restorations and implant abutments, laboratory tests and developments, clinical performance, and possible future trends for implant dentistry are addressed. A review of available literature from 1990 through 2010 was conducted with search terms zirconia,"implants,"abutment,"crown," and "fixed dental prosthesis" using electronic databases (PubMed) and manual searching. Latest applications of zirconia in implant dentistry include implant abutments, multiple unit and full-arch frameworks as well as custom-made bars to support fixed and removable prostheses. High biocompatibility, low bacterial surface adhesion as well as favorable chemical properties of zirconia ceramics are reported. Zirconia stabilized with yttrium oxide exhibits high flexural strength and fracture toughness due to a transformation toughening mechanism. Preliminary clinical data confirmed the high stability of zirconia for abutments and as a framework material for implant borne crowns and fixed dental prostheses. Zirconia abutment or framework damage has rarely been encountered. However, veneering porcelain fractures are the most common technical complication in implant-supported zirconia restorations. These porcelain veneer failures have led to concerns regarding differences in coefficient of thermal expansions between core and veneering porcelain and their respective processing techniques. As presently evidence of clinical long-term data is missing, caution with regard to especially extensive implant-borne zirconia frameworks is recommended. © 2010 Wiley Periodicals, Inc.

  2. A fixed-point farrago

    CERN Document Server

    Shapiro, Joel H

    2016-01-01

    This text provides an introduction to some of the best-known fixed-point theorems, with an emphasis on their interactions with topics in analysis. The level of exposition increases gradually throughout the book, building from a basic requirement of undergraduate proficiency to graduate-level sophistication. Appendices provide an introduction to (or refresher on) some of the prerequisite material and exercises are integrated into the text, contributing to the volume’s ability to be used as a self-contained text. Readers will find the presentation especially useful for independent study or as a supplement to a graduate course in fixed-point theory. The material is split into four parts: the first introduces the Banach Contraction-Mapping Principle and the Brouwer Fixed-Point Theorem, along with a selection of interesting applications; the second focuses on Brouwer’s theorem and its application to John Nash’s work; the third applies Brouwer’s theorem to spaces of infinite dimension; and the fourth rests ...

  3. GOLD and the fixed ratio

    Directory of Open Access Journals (Sweden)

    Vestbo J

    2012-09-01

    Full Text Available Jørgen VestboUniversity of Manchester, Manchester, UKI read with interest the paper entitled "Diagnosis of airway obstruction in the elderly: contribution of the SARA study" by Sorino et al in a recent issue of this journal.1 Being involved in the Global Initiative for Obstructive Lung Diseases (GOLD, it is nice to see the interest sparked by the GOLD strategy document. However, in the paper by Sorino et al, there are a few misunderstandings around GOLD and the fixed ratio (forced expiratory volume in 1 second/forced volume vital capacity < 0.70 that need clarification.View original paper by Sorino and colleagues.

  4. Retrospective dosimetry: Estimation of the dose to quartz using the single-aliquot regenerative-dose protocol

    DEFF Research Database (Denmark)

    Banerjee, D.; Bøtter-Jensen, L.; Murray, A.S.

    2000-01-01

    meets the fundamental requirement of the single-aliquot regenerative-dose protocol, in that any change in the luminescence recombination probability can be corrected for by using the OSL response to a fixed test dose. The response of a particular aliquot is examined after three different treatments...... temperature and test-dose size. Finally, dose-depth profiles are presented for two bricks. These profiles demonstrate that the high precisions (similar to 1%) obtained using the regenerative-dose protocol are reflected in smooth dose-depth dependencies. (C) 2000 Elsevier Science Ltd. All rights reserved....

  5. Homotopies and the Universal Fixed Point Property

    DEFF Research Database (Denmark)

    Szymik, Markus

    2015-01-01

    A topological space has the fixed point property if every continuous self-map of that space has at least one fixed point. We demonstrate that there are serious restraints imposed by the requirement that there be a choice of fixed points that is continuous whenever the self-map varies continuously...

  6. Fixed Target Collisions at STAR

    Science.gov (United States)

    Meehan, Kathryn C.

    2016-12-01

    The RHIC Beam Energy Scan (BES) program was proposed to look for the turn-off of signatures of the quark gluon plasma (QGP), search for a possible QCD critical point, and study the nature of the phase transition between hadronic and partonic matter. Previous results have been used to claim that the onset of deconfinement occurs at a center-of-mass energy of 7 GeV. Data from lower energies are needed to test if this onset occurs. The goal of the STAR Fixed-Target Program is to extend the collision energy range in BES II to energies that are likely below the onset of deconfinement. Currently, STAR has inserted a gold target into the beam pipe and conducted test runs at center-of-mass energies of 3.9 and 4.5 GeV. Tests have been done with both Au and Al beams. First physics results from a Coulomb potential analysis of Au + Au fixed-target collisions are presented and are found to be consistent with results from previous experiments. Furthermore, the Coulomb potential, which is sensitive to the Z of the projectile and degree of baryonic stopping, will be compared to published results from the AGS.

  7. Utilization of nitrogen fixing trees

    Energy Technology Data Exchange (ETDEWEB)

    Brewbaker, J.L.; Beldt, R. van den; MacDicken, K.; Budowski, G.; Kass, D.C.L.; Russo, R.O.; Escalante, G.; Herrera, R.; Aranguren, J.; Arkcoll, D.B.; Doebereinger, J. (cord.)

    1983-01-01

    Six papers from the symposium are noted. Brewbaker, J.L., Beldt, R. van den, MacDicken, K. Fuelwood uses and properties of nitrogen-fixing trees, pp 193-204, (Refs. 15). Includes a list of 35 nitrogen-fixing trees of high fuelwood value. Budowski, G.; Kass, D.C.L.; Russo, R.O. Leguminous trees for shade, pp 205-222, (Refs. 68). Escalante, G., Herrera, R., Aranguren, J.; Nitrogen fixation in shade trees (Erythrina poeppigiana) in cocoa plantations in northern Venezuela, pp 223-230, (Refs. 13). Arkcoll, D.B.; Some leguminous trees providing useful fruits in the North of Brazil, pp 235-239, (Refs. 13). This paper deals with Parkia platycephala, Pentaclethra macroloba, Swartzia sp., Cassia leiandra, Hymenaea courbaril, dipteryz odorata, Inga edulis, I. macrophylla, and I. cinnamonea. Baggio, A.J.; Possibilities of the use of Gliricidia sepium in agroforestry systems in Brazil, pp 241-243; (Refs. 15). Seiffert, N.F.; Biological nitrogen and protein production of Leucaena cultivars grown to supplement the nutrition of ruminants, pp 245-249, (Refs. 14). Leucaena leucocephala cv. Peru, L. campina grande (L. leucocephala), and L. cunningham (L. leucocephalae) were promising for use as browse by beef cattle in central Brazil.

  8. Complex issues in accounting for fixed assets

    Directory of Open Access Journals (Sweden)

    Mykhaylo Luchko

    2013-11-01

    Full Text Available This paper considers the mentioned complex issues of business fixed assets accounting. The main emphasis in this case refers to the change in value of fixed assets over time. Author studied problems of the regulatory revaluation of fixed assets in accordance with the applicable accounting standards (regulations. Particular attention is paid to the revaluation and impairment of the business fixed assets objects and their recording on accounts. Author analyzed the complex issues in establishing the fair value of fixed assets. Attention is focused on the harmonization of accounting information with tax calculations and reporting provided by the Ukrainian Tax Code. In considering the matter referred to the tax differences (temporary and permanent. Established tax differences in depreciation of fixed assets, impairment amounts and revaluation of fixed assets and accounting entries to them.

  9. Simple fixed functional space maintainer.

    Science.gov (United States)

    Goenka, Puneet; Sarawgi, Aditi; Marwah, Nikhil; Gumber, Parvind; Dutta, Samir

    2014-01-01

    Premature loss of a primary tooth is one of the most common etiology for malocclusion. Space maintainers are employed to prevent this complication. In anterior region, esthetics is an important concern along with function and space management. Fiber-reinforced composite (FRC) retained space maintainer solves all these purposes ef ficiently and ef fectively. In addition, the technique is simple and the appliance is very comfortable inside the oral cavity. Here is a case of premature loss of anterior primary tooth which was replaced by FRC retained esthetic functional space maintainer. The appliance was found to be functioning satisfactorily inside the oral cavity till the last visit (1 Year). How to cite this article: Goenka P, Sarawgi A, Marwah N, Gumber P, Dutta S. Simple Fixed Functional Space Maintainer. Int J Clin Pediatr Dent 2014;7(3):225-228.

  10. Fixed Point and Aperiodic Tilings

    CERN Document Server

    Durand, Bruno; Shen, Alexander

    2008-01-01

    An aperiodic tile set was first constructed by R.Berger while proving the undecidability of the domino problem. It turned out that aperiodic tile sets appear in many topics ranging from logic (the Entscheidungsproblem) to physics (quasicrystals) We present a new construction of an aperiodic tile set that is based on Kleene's fixed-point construction instead of geometric arguments. This construction is similar to J. von Neumann self-reproducing automata; similar ideas were also used by P. Gacs in the context of error-correcting computations. The flexibility of this construction allows us to construct a ``robust'' aperiodic tile set that does not have periodic (or close to periodic) tilings even if we allow some (sparse enough) tiling errors. This property was not known for any of the existing aperiodic tile sets.

  11. Fixed Point Actions for Lattice Fermions

    CERN Document Server

    Bietenholz, W

    1994-01-01

    The fixed point actions for Wilson and staggered lattice fermions are determined by iterating renormalization group transformations. In both cases a line of fixed points is found. Some points have very local fixed point actions. They can be used to construct perfect lattice actions for asymptotically free fermionic theories like QCD or the Gross-Neveu model. The local fixed point actions for Wilson fermions break chiral symmetry, while in the staggered case the remnant $U(1)_e \\otimes U(1)_o$ symmetry is preserved. In addition, for Wilson fermions a nonlocal fixed point is found that corresponds to free chiral fermions. The vicinity of this fixed point is studied in the Gross-Neveu model using perturbation theory.

  12. Fixed telephony evolution at CERN

    CERN Document Server

    CERN. Geneva

    2015-01-01

    The heart of CERN’s telephony infrastructure consists of the Alcatel IP-PBX that links CERN’s fixed line phones, Lync softphones and CERN’s GSM subscribers to low-cost local and international telephony services. The PABX infrastructure also supports the emergency “red telephones” in the LHC tunnel and provides vital services for the Fire and Rescue Service and the CERN Control Centre. Although still reliable, the Alcatel hardware is increasingly costly to maintain and looking increasingly outmoded in a market where open source solutions are increasingly dominant. After presenting an overview of the Alcatel PABX and the services it provides, including innovative solutions such as the Closed User Group for our mobile telephony services, we present a possible architecture for a software based system designed to meet tomorrow’s communication needs and describe how the introduction of open-source call routers based on the SIP protocol and Session Border Controllers (SBC) could foster the introduction...

  13. Fixed drug eruptions with modafinil

    Directory of Open Access Journals (Sweden)

    Loknath Ghoshal

    2015-01-01

    Full Text Available Modafinil is a psychostimulant drug, which has been approved by the US Food and Drug Administration for the treatment of narcolepsy associated excessive daytime sleepiness, sleep disorder related to shift work, and obstructive sleep apnea syndrome. However, presently it is being used as a lifestyle medicine; in India, it has been misused as an "over the counter" drug. Modafinil is known to have several cutaneous side effects. Fixed drug eruption (FDE is a distinctive drug induced reaction pattern characterized by recurrence of eruption at the same site of the skin or mucous membrane with repeated systemic administration. Only two case reports exist in the literature describing modafinil induced FDE until date. Here, we report two similar cases. The increasing use of this class of drug amongst the medical personnel might be posing a threat to the proper use and encouraging subsequent abuse. There might be a considerable population using these drugs unaware of the possible adverse effects. Authorities should be more alert regarding the sale and distribution of such medicines.

  14. Fixed Export Costs and Export Behavior

    OpenAIRE

    Castro, Luis; Li, Ben; Keith E. Maskus; Xie, Yiqing

    2014-01-01

    This paper provides a direct test of how fixed export costs and productivity jointly determine firm-level export behavior. Using Chilean data, we construct indices of fixed export costs for each industry-region-year triplet and match them to domestic firms. Our empirical results show that firms facing higher fixed export costs are less likely to export, while those with higher productivity export more. These outcomes are the foundation of the widely-used sorting mechanism in the trade models ...

  15. Fixed-point-like theorems on subspaces

    Directory of Open Access Journals (Sweden)

    Bernard Cornet

    2004-08-01

    Full Text Available We prove a fixed-point-like theorem for multivalued mappings defined on the finite Cartesian product of Grassmannian manifolds and convex sets. Our result generalizes two different kinds of theorems: the fixed-point-like theorem by Hirsch et al. (1990 or Husseini et al. (1990 and the fixed-point theorem by Gale and Mas-Colell (1975 (which generalizes Kakutani's theorem (1941.

  16. Failure-probability driven dose painting

    Energy Technology Data Exchange (ETDEWEB)

    Vogelius, Ivan R.; Håkansson, Katrin; Due, Anne K.; Aznar, Marianne C.; Kristensen, Claus A.; Rasmussen, Jacob; Specht, Lena [Department of Radiation Oncology, Rigshospitalet, University of Copenhagen, Copenhagen 2100 (Denmark); Berthelsen, Anne K. [Department of Radiation Oncology, Rigshospitalet, University of Copenhagen, Copenhagen 2100, Denmark and Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, University of Copenhagen, Copenhagen 2100 (Denmark); Bentzen, Søren M. [Department of Radiation Oncology, Rigshospitalet, University of Copenhagen, Copenhagen 2100, Denmark and Departments of Human Oncology and Medical Physics, University of Wisconsin, Madison, Wisconsin 53792 (United States)

    2013-08-15

    Purpose: To demonstrate a data-driven dose-painting strategy based on the spatial distribution of recurrences in previously treated patients. The result is a quantitative way to define a dose prescription function, optimizing the predicted local control at constant treatment intensity. A dose planning study using the optimized dose prescription in 20 patients is performed.Methods: Patients treated at our center have five tumor subvolumes from the center of the tumor (PET positive volume) and out delineated. The spatial distribution of 48 failures in patients with complete clinical response after (chemo)radiation is used to derive a model for tumor control probability (TCP). The total TCP is fixed to the clinically observed 70% actuarial TCP at five years. Additionally, the authors match the distribution of failures between the five subvolumes to the observed distribution. The steepness of the dose–response is extracted from the literature and the authors assume 30% and 20% risk of subclinical involvement in the elective volumes. The result is a five-compartment dose response model matching the observed distribution of failures. The model is used to optimize the distribution of dose in individual patients, while keeping the treatment intensity constant and the maximum prescribed dose below 85 Gy.Results: The vast majority of failures occur centrally despite the small volumes of the central regions. Thus, optimizing the dose prescription yields higher doses to the central target volumes and lower doses to the elective volumes. The dose planning study shows that the modified prescription is clinically feasible. The optimized TCP is 89% (range: 82%–91%) as compared to the observed TCP of 70%.Conclusions: The observed distribution of locoregional failures was used to derive an objective, data-driven dose prescription function. The optimized dose is predicted to result in a substantial increase in local control without increasing the predicted risk of toxicity.

  17. Fixed point theorems in spaces and -trees

    Directory of Open Access Journals (Sweden)

    Kirk WA

    2004-01-01

    Full Text Available We show that if is a bounded open set in a complete space , and if is nonexpansive, then always has a fixed point if there exists such that for all . It is also shown that if is a geodesically bounded closed convex subset of a complete -tree with , and if is a continuous mapping for which for some and all , then has a fixed point. It is also noted that a geodesically bounded complete -tree has the fixed point property for continuous mappings. These latter results are used to obtain variants of the classical fixed edge theorem in graph theory.

  18. Fixed Simplex Property for Retractable Complexes

    Directory of Open Access Journals (Sweden)

    Zapart Anna

    2010-01-01

    Full Text Available Abstract Retractable complexes are defined in this paper. It is proved that they have the fixed simplex property for simplicial maps. This implies the theorem of Wallace and the theorem of Rival and Nowakowski for finite trees: every simplicial map transforming vertices of a tree into itself has a fixed vertex or a fixed edge. This also implies the Hell and Nešetřil theorem: any endomorphism of a dismantlable graph fixes some clique. Properties of recursively contractible complexes are examined.

  19. Classification system adopted for fixed cutter bits

    Energy Technology Data Exchange (ETDEWEB)

    Winters, W.J.; Doiron, H.H.

    1988-01-01

    The drilling industry has begun adopting the 1987 International Association of Drilling Contractors' (IADC) method for classifying fixed cutter drill bits. By studying the classification codes on bit records and properly applying the new IADC fixed cutter dull grading system to recently run bits, the end-user should be able to improve the selection and usage of fixed cutter bits. Several users are developing databases for fixed cutter bits in an effort to relate field performance to some of the more prominent bit design characteristics.

  20. Factors influencing bonding fixed restorations

    Directory of Open Access Journals (Sweden)

    Medić Vesna

    2008-01-01

    Full Text Available INTRODUCTION Crown displacement often occurs because the features of tooth preparations do not counteract the forces directed against restorations. OBJECTIVE The purpose of this study was to evaluate the effect of preparation designs on retention and resistance of fixed restorations. METHOD The study was performed on 64 differently sized stainless steel dies. Also, caps which were used for evaluated retention were made of stainless steel for each die. After cementing the caps on experimental dies, measuring of necessary tensile forces to separate cemented caps from dies was done. Caps, which were made of a silver-palladium alloy with a slope of 60° to the longitudinal axis formed on the occlusal surface, were used for evaluating resistance. A sudden drop in load pressure recorded by the test machine indicated failure for that cap. RESULTS A significant difference was found between the tensile force required to remove the caps from the dies with different length (p<0.05 and different taper (p<0.01. The greatest retentive strengths (2579.2 N and 2989.8 N were noticed in experimental dies with the greatest length and smallest taper. No statistically significant (p>0.05 differences were found between tensile loads for caps cemented on dies with different diameter. Although there was an apparent slight increase in resistance values for caps on dies with smaller tapers, the increase in resistance for those preparation designs was not statistically significant. There was a significant difference among the resistance values for caps on dies with different length (p<0.01 and diameter (p<0.05. CONCLUSION In the light of the results obtained, it could be reasonably concluded that retention and resistance of the restoration is in inverse proportion to convergence angle of the prepared teeth. But, at a constant convergence angle, retention and resistance increase with rising length and diameter.

  1. Ciprofloxacin induced fixed drug eruption

    Directory of Open Access Journals (Sweden)

    M. Ravishankar

    2014-12-01

    Full Text Available Fixed drug eruption (FDE is a clinical entity occurring in the same site or sites each time the drug is administered. Acute lesions appear as sharply marginated erythematous plaques, which are usually found on lips, genitalia, abdomen, and legs. The eruptions usually occur within hours of administration of the offending agent and resolves spontaneously without scarring after few weeks of onset. Most common drugs causing FDE are sulfonamides, tetracyclines, salicylates, barbiturates, doxycycline, fluconazole, clarithromycin, etc. Ciprofloxacin, a widely used fluoroquinolone antimicrobial, induces cutaneous adverse drug reactions (ADRs in about 1-2% of treated patients. Urticaria, angioedema, maculopapular exanthems, and photosensitivity are the most frequently documented cutaneous adverse reactions. In this case report, the patient soon after taking ciprofloxacin tablets, developed itching in the lips, palms and in scrotal region. On continuing the treatment, the next day he developed fluid filled lesions over palm, knuckle, and hyperpigmentation. He gives a history of severe itching and rashes in scrotal region. He gives a history of similar complaints in the previous month after taking ciprofloxacin medication. There was no history of intake of any other medication. On examination, bullous lesions and pustules in finger webs, hyperpigmentation on knuckles, and scrotal erosions were seen. In the present case report, the patient presented with FDE immediately after oral administration of ciprofloxacin and got completely cured after stopping the drug and taking adequate treatment. According to the Naranjo's ADR probability scale (score=8, this ADR is categorized as a and ldquo;probable and rdquo; reaction to the drug. [Int J Basic Clin Pharmacol 2014; 3(6.000: 1096-1097

  2. An Evaluation of Thyromental Distance-based Method or Weight-based Method in Determining the Size of the Laryngeal Mask Airway Supreme

    Science.gov (United States)

    Weng, Meilin; Ding, Ming; Xu, Yajun; Yang, Xijun; Li, Lihong; Zhong, Jing; Miao, Changhong

    2016-01-01

    Abstract The successful placement of Laryngeal Mask Airway (LMA) Supreme in adults largely depends on right selection of its size. Most anesthesiologists determine the size of LMA according to patients’ body weight, which does not always work well. An alternative method should be established to guarantee higher efficacy of ventilation through LMA Supreme placement. This controlled study was designed to compare the efficacy of LMA Supreme placement, when the size of it is determined by body weight or by thyromental distance. Eighty healthy individuals with American Society of Anesthesiologists physical status 1 to 2 scheduled for elective ambulatory surgery were randomly allocated into 2 groups: thyromental distance-based group (n = 40) and weight-based group (n = 40). Efficacy of controlled ventilation through LMA, easy of device placement, and pharyngeal sealing were evaluated between the groups. The tidal volume under 10 cm H2O pressure-controlled ventilation in thyromental distance-based group was significantly higher than that in weight-based group (523.9 ± 135.4 vs 477.1 ± 185.6; P = 0.031). The number of patients who achieved “excellent” tidal volume (>8 mL/kg) were significantly more in the thyromental distance-based group (24/40 vs 13/40; P = 0.019). Among overweight patients (body mass index >23), those who achieved “excellent” tidal volume (>8 mL/kg) under 10 cm H2O pressure-controlled ventilation were also more in thyromental distanced-based group than in weight-based group (11/24 vs 2/24; P = 0.031). The time taken for successful insertion was shorter with the thyromental distance-based group compared with the weight-based group (54.6 ± 33.6 vs 87.8 ± 98.9; P = 0.021). Oropharyngeal leak pressure was pretty close between the 2 groups (26.4 ± 5.1 vs 25.0 ± 5.7 cm H2O; P = 0.180). In terms of guaranteeing better positive pressure ventilation, facilitating device placement, and

  3. Unusual radioresistance of nitrogen-fixing cultures of Anabaena strains

    Indian Academy of Sciences (India)

    Harinder Singh; Tonina Fernandes; Shree Kumar Apte

    2010-09-01

    Nitrogen-fixing cultures of two species of the filamentous, heterocystous cyanobacterium Anabaena, namely Anabaena sp. strain L-31 and Anabaena torulosa were found to be highly tolerant to 60Co gamma radiation. No adverse effect on diazotrophic growth and metabolism were observed up to a dose of 5 kGy. At higher doses, radiation tolerance showed a correspondence with the inherent osmotolerance, with Anabaena L-31 being the more radiation tolerant as well as osmotolerant strain. In Anabaena L-31, exposure to 6 kGy of gamma rays resulted in genome disintegration, but did not reduce viability. Irradiation delayed heterocyst differentiation and nitrogen fixation, and marginally affected diazotrophic growth. All the affected parameters recovered after a short lag, without any discernible post-irradiation phenotype. The radiation tolerance of these Gram-negative photoautodiazotrophs is comparable with that of the adiazotrophic photoautotrophic cyanobacterium Chroococcidiopsis or adiazotrophic heterotroph Deinococcus radiodurans. This is the first report of extreme radioresistance in nitrogen-fixing Anabaena cultures.

  4. Fixed Point Curve for Weakly Inward Contractions and Approximate Fixed Point Property

    Institute of Scientific and Technical Information of China (English)

    P. Riyas; K. T. Ravindran

    2013-01-01

    In this paper, we discuss the concept of fixed point curve for linear interpo-lations of weakly inward contractions and establish necessary condition for a nonex-pansive mapping to have approximate fixed point property.

  5. VAT and Fixed Establishment : Mysteries Solved?

    NARCIS (Netherlands)

    M.L. Schippers (Martijn); Boender, J.M.B.

    2015-01-01

    markdownabstractThe Sixth Value Added Tax (VAT) Directive introduced the concept of the fixed establishment in VAT. For a long time, the criteria for classifying activities as a fixed establishment seemed relatively clear. However the introduction in 2011 of the VAT Implementing Regulation3

  6. Approximate Equilibrium Problems and Fixed Points

    Directory of Open Access Journals (Sweden)

    H. Mazaheri

    2013-01-01

    Full Text Available We find a common element of the set of fixed points of a map and the set of solutions of an approximate equilibrium problem in a Hilbert space. Then, we show that one of the sequences weakly converges. Also we obtain some theorems about equilibrium problems and fixed points.

  7. On computing fixed points for generalized sandpiles

    OpenAIRE

    Formenti, Enrico; Masson, Benoît

    2004-01-01

    Presented at DMCS 2004 (Turku, FINLAND). Long version with proofs published in International Journal of Unconventional Computing, 2006; International audience; We prove fixed points results for sandpiles starting with arbitrary initial conditions. We give an effective algorithm for computing such fixed points, and we refine it in the particular case of SPM.

  8. Fixed-Response Questions with a Difference.

    Science.gov (United States)

    Johnstone, Alex H.; Ambusaidi, Abdullah

    2002-01-01

    Offers three types of fixed-response questions that are designed to overcome drawbacks appearing in the conventional forms of fixed-response questions such as not allowing the examiner to investigate reasoning, background, or prevent guessing. (Contains 14 references.) (Author/YDS)

  9. Approximate fixed point of Reich operator

    Directory of Open Access Journals (Sweden)

    M. Saha

    2013-01-01

    Full Text Available In the present paper, we study the existence of approximate fixed pointfor Reich operator together with the property that the ε-fixed points are concentrated in a set with the diameter tends to zero if ε $to$ > 0.

  10. Stabilising springs for fixed lingual retainer.

    Science.gov (United States)

    Karthikeyan, M K; Ramachandraprabhakar; Saravanan, R; Rajvikram, N; Kuppuchamy

    2013-11-01

    Most treated malocclusion needs fixed lingual retention. To stabilise fixed lingual retainer in the exact location needs proper stabilisation. Proper stabilization requires a holding spring. This Stabilising Spring should be easy to fabricate and help the clinician to stabilise the retainer quickly and save the chair side time. More over it should not irritate the mucosa and should be easy to insert and remove.

  11. Magnetic Fixed Points and Emergent Supersymmetry

    DEFF Research Database (Denmark)

    Antipin, Oleg; Mojaza, Matin; Pica, Claudio;

    2013-01-01

    We establish in perturbation theory the existence of fixed points along the renormalization group flow for QCD with an adjoint Weyl fermion and scalar matter reminiscent of magnetic duals of QCD [1-3]. We classify the fixed points by analyzing their basin of attraction. We discover that among the...

  12. Fixed-Response Questions with a Difference.

    Science.gov (United States)

    Johnstone, Alex H.; Ambusaidi, Abdullah

    2002-01-01

    Offers three types of fixed-response questions that are designed to overcome drawbacks appearing in the conventional forms of fixed-response questions such as not allowing the examiner to investigate reasoning, background, or prevent guessing. (Contains 14 references.) (Author/YDS)

  13. Acoustic dose and acoustic dose-rate.

    Science.gov (United States)

    Duck, Francis

    2009-10-01

    Acoustic dose is defined as the energy deposited by absorption of an acoustic wave per unit mass of the medium supporting the wave. Expressions for acoustic dose and acoustic dose-rate are given for plane-wave conditions, including temporal and frequency dependencies of energy deposition. The relationship between the acoustic dose-rate and the resulting temperature increase is explored, as is the relationship between acoustic dose-rate and radiation force. Energy transfer from the wave to the medium by means of acoustic cavitation is considered, and an approach is proposed in principle that could allow cavitation to be included within the proposed definitions of acoustic dose and acoustic dose-rate.

  14. Fixed points of occasionally weakly biased mappings

    Directory of Open Access Journals (Sweden)

    Y. Mahendra Singh, M. R. Singh

    2012-09-01

    Full Text Available Common fixed point results due to Pant et al. [Pant et al., Weak reciprocal continuity and fixed point theorems, Ann Univ Ferrara, 57(1, 181-190 (2011] are extended to a class of non commuting operators called occasionally weakly biased pair[ N. Hussain, M. A. Khamsi A. Latif, Commonfixed points for JH-operators and occasionally weakly biased pairs under relaxed conditions, Nonlinear Analysis, 74, 2133-2140 (2011]. We also provideillustrative examples to justify the improvements. Abstract. Common fixed point results due to Pant et al. [Pant et al., Weakreciprocal continuity and fixed point theorems, Ann Univ Ferrara, 57(1, 181-190 (2011] are extended to a class of non commuting operators called occasionally weakly biased pair[ N. Hussain, M. A. Khamsi A. Latif, Common fixed points for JH-operators and occasionally weakly biased pairs under relaxed conditions, Nonlinear Analysis, 74, 2133-2140 (2011]. We also provide illustrative examples to justify the improvements.

  15. The price of fixed income market volatility

    CERN Document Server

    Mele, Antonio

    2015-01-01

    Fixed income volatility and equity volatility evolve heterogeneously over time, co-moving disproportionately during periods of global imbalances and each reacting to events of different nature. While the methodology for options-based "model-free" pricing of equity volatility has been known for some time, little is known about analogous methodologies for pricing various fixed income volatilities. This book fills this gap and provides a unified evaluation framework of fixed income volatility while dealing with disparate markets such as interest-rate swaps, government bonds, time-deposits and credit. It develops model-free, forward looking indexes of fixed-income volatility that match different quoting conventions across various markets, and uncovers subtle yet important pitfalls arising from naïve superimpositions of the standard equity volatility methodology when pricing various fixed income volatilities. The ultimate goal of the authors´ efforts is to make interest rate volatility standardization a valuable...

  16. Magnetic Fixed Points and Emergent Supersymmetry

    CERN Document Server

    Antipin, Oleg; Pica, Claudio; Sannino, Francesco

    2011-01-01

    We establish the existence of fixed points for certain gauge theories candidate to be magnetic duals of QCD with one adjoint Weyl fermion. In the perturbative regime of the magnetic theory the existence of a very large number of fixed points is unveiled. We classify them by analyzing their basin of attraction. The existence of several nonsupersymmetric fixed points for the magnetic gauge theory lends further support towards the existence of gauge-gauge duality beyond supersymmetry. We also discover that among these very many fixed points there are supersymmetric ones emerging from a generic nonsupersymmetric renormalization group flow. We therefore conclude that supersymmetry naturally emerges as a fixed point theory from a nonsupersymmetric Lagrangian without the need for fine-tuning of the bare couplings. Our results suggest that supersymmetry can be viewed as an emergent phenomenon in field theory. In particular there should be no need for fine-tuning the bare couplings when performing Lattice simulations ...

  17. Avaliação da eficácia e segurança da associação de budesonida e formoterol em dose fixa e cápsula única no tratamento de asma não controlada: ensaio clínico randomizado, duplo-cego, multicêntrico e controlado Evaluation of the efficacy and safety of a fixed-dose, single-capsule budesonide-formoterol combination in uncontrolled asthma: a randomized, double-blind, multicenter, controlled clinical trial

    Directory of Open Access Journals (Sweden)

    Roberto Stirbulov

    2012-08-01

    Full Text Available OBJETIVO: Avaliar a eficácia e a segurança da associação de budesonida e formoterol em dose fixa e cápsula única, em comparação ao uso de budesonida isolada em pacientes com asma não controlada. MÉTODOS: Ensaio clínico randomizado, duplo-cego, multicêntrico, de fase III, com grupos paralelos, comparando a eficácia de curto prazo e a segurança da formulação em pó de budesonida (400 µg e formoterol (12 µg com a formulação em pó de budesonida (400 µg em 181 participantes com asma não totalmente controlada. A idade dos participantes variou de 18-77 anos. Após um período de run-in de 4 semanas, durante o qual todos os participantes receberam budesonida duas vezes por dia, houve a randomização para um dos tratamentos do estudo. O tratamento foi administrado duas vezes ao dia por 12 semanas. Os principais desfechos foram VEF1, CVF e PFE matinal. Os dados foram analisados por intenção de tratar. RESULTADOS: O grupo tratado com a associação, quando comparado ao grupo budesonida isolado, teve uma melhora significativa no VEF1 (0,12 L vs. 0,02 L; p = 0.0129 e no PFE matinal (30,2 L/min vs. 6,3 L/min; p = 0,0004. Esses efeitos foram acompanhados por boa tolerabilidade e segurança, como demonstrado pela baixa frequência de eventos adversos menores. CONCLUSÕES: A associação em cápsula única de budesonida e formoterol mostrou ser eficaz e segura. Os resultados demonstram que essa formulação é uma opção terapêutica válida para a obtenção e manutenção do controle da asma.OBJECTIVE: To evaluate the efficacy and safety of a fixed-dose, single-capsule budesonide-formoterol combination, in comparison with budesonide alone, in patients with uncontrolled asthma. METHODS: This was a randomized, double-blind, multicenter, phase III, parallel clinical trial, comparing the short-term efficacy and safety of the combination of budesonide (400 µg and formoterol (12 µg, with those of budesonide alone (400 µg, both delivered

  18. Fixed-point adiabatic quantum search

    Science.gov (United States)

    Dalzell, Alexander M.; Yoder, Theodore J.; Chuang, Isaac L.

    2017-01-01

    Fixed-point quantum search algorithms succeed at finding one of M target items among N total items even when the run time of the algorithm is longer than necessary. While the famous Grover's algorithm can search quadratically faster than a classical computer, it lacks the fixed-point property—the fraction of target items must be known precisely to know when to terminate the algorithm. Recently, Yoder, Low, and Chuang [Phys. Rev. Lett. 113, 210501 (2014), 10.1103/PhysRevLett.113.210501] gave an optimal gate-model search algorithm with the fixed-point property. Previously, it had been discovered by Roland and Cerf [Phys. Rev. A 65, 042308 (2002), 10.1103/PhysRevA.65.042308] that an adiabatic quantum algorithm, operating by continuously varying a Hamiltonian, can reproduce the quadratic speedup of gate-model Grover search. We ask, can an adiabatic algorithm also reproduce the fixed-point property? We show that the answer depends on what interpolation schedule is used, so as in the gate model, there are both fixed-point and non-fixed-point versions of adiabatic search, only some of which attain the quadratic quantum speedup. Guided by geometric intuition on the Bloch sphere, we rigorously justify our claims with an explicit upper bound on the error in the adiabatic approximation. We also show that the fixed-point adiabatic search algorithm can be simulated in the gate model with neither loss of the quadratic Grover speedup nor of the fixed-point property. Finally, we discuss natural uses of fixed-point algorithms such as preparation of a relatively prime state and oblivious amplitude amplification.

  19. About Applications of the Fixed Point Theory

    Directory of Open Access Journals (Sweden)

    Bucur Amelia

    2017-06-01

    Full Text Available The fixed point theory is essential to various theoretical and applied fields, such as variational and linear inequalities, the approximation theory, nonlinear analysis, integral and differential equations and inclusions, the dynamic systems theory, mathematics of fractals, mathematical economics (game theory, equilibrium problems, and optimisation problems and mathematical modelling. This paper presents a few benchmarks regarding the applications of the fixed point theory. This paper also debates if the results of the fixed point theory can be applied to the mathematical modelling of quality.

  20. [FIXED COMBINATION ATORVASTATIN-EZETIMIBE (ATOZET®)].

    Science.gov (United States)

    Scheen, A J

    2016-01-01

    Cardiovascular prevention in subjects at high or very high risk requires a drastic reduction in LDL cholesterol according to the concept "the lower, the better". The combination of an inhibitor of cholesterol synthesis and a selective inhibitor of intestinal absorption results in a complementary and synergistic LDL-lowering activity. Besides a first fixed combination ezetimibe-simvastatin (Inegy®), a new fixed combination is presented, Atozet® that combines atorvastatin and ezetimibe. Because atorvastatin is more potent than simvastatin, this novel fixed combination should facilitate reaching therapeutic goals in terms of LDL cholesterol amongst patients with severe hypercholesterolaemia and/or at high or very high cardiovascular risk.

  1. Imaginary fixed points can be physical.

    Science.gov (United States)

    Zhong, Fan

    2012-08-01

    It has been proposed that a first-order phase transition driven to happen in the metastable region exhibits scaling and universality near an instability point controlled by an instability fixed point of a φ(3) theory. However, this fixed point has an imaginary value and the renormalization-group flow of the φ(3) coupling diverges at a finite scale. Here combining a momentum-space RG analysis and a nucleation theory near the spinodal point, we show that imaginary rather than real values are physical counterintuitively and thus the imaginary fixed point does control the scaling.

  2. Benchmark Dose Modeling

    Science.gov (United States)

    Finite doses are employed in experimental toxicology studies. Under the traditional methodology, the point of departure (POD) value for low dose extrapolation is identified as one of these doses. Dose spacing necessarily precludes a more accurate description of the POD value. ...

  3. Quantification of Niacin and Its Metabolite Nicotinuric Acid in Human Plasma by LC-MS/MS: Application to a Clinical Trial of a Fixed Dose Combination Tablet of Niacin Extended-Release/Simvastatin (500 mg/10 mg in Healthy Chinese Volunteers

    Directory of Open Access Journals (Sweden)

    Pingping Zhang

    2015-01-01

    Full Text Available Our paper aimed to develop rapid, sensitive, and specific LC-MS/MS method for the quantification of niacin (NA and its metabolite nicotinuric acid (NUA in human plasma. Following protein precipitation with acetonitrile, the NA, NUA, and internal standard (5-fluorouracil were separated on a Zorbax 300SB-C8 column (250 mm × 4.6 mm, 5 μm with a mobile phase consisting of methanol-2 mM ammonium acetate (3 : 97, v/v at a flow rate of 1 mL/min (split 1 : 1. A tandem mass spectrometer equipped with electrospray ionization source was used as the detector and operated in negative ion mode. The linear concentration ranges of the calibration curves were 5–800 ng/mL for NA and NUA. The intra-assay RSD for quality control (QC samples were from 5.0% to 8.7% for NA, and 5.5% to 7.6% for NUA. The interassay RSD for QC samples were from 2.8% to 9.4% for NA, and 3.7% to 5.8% for NUA. The relative errors for QC samples were from −2.2% to 2.3% for NA, and −0.6% to 3.2% for NUA. The method was successfully applied to the investigation of the pharmacokinetic profiles of NA, NUA in human after single dose administration of Niacin extended-release/Simvastatin tablet (500 mg/10 mg.

  4. Maximizing antimalarial efficacy and the importance of dosing strategies.

    Science.gov (United States)

    Beeson, James G; Boeuf, Philippe; Fowkes, Freya J I

    2015-05-09

    Artemisinin-based combination therapies (ACTs) are the cornerstone for the treatment of malaria. However, confirmed resistance to artemisinins in South-East Asia, and reports of reduced efficacy of ACTs raise major concerns for malaria treatment and control. Without new drugs to replace artemisinins, it is essential to define dosing strategies that maximize therapeutic efficacy, limit the spread of resistance, and preserve the clinical value of ACTs. It is important to determine the extent to which reduced efficacy of ACTs reflects true resistance versus sub-optimal dosing, and quantify other factors that determine treatment failure. Pooled analyses of individual patient data from multiple clinical trials, by investigators in the Worldwide Antimalarial Resistance Network, have shown high overall efficacy for three widely used ACTs, artemether-lumefantrine, artesunate-amodiaquine, and dihydroartemisinin-piperaquine. Analyses also highlight that suboptimal dosing leads to increased risk of treatment failure, especially among children. In the most recent study, an analysis of clinical trials of artesunate-amodiaquine, widely used among children in Africa, revealed a superior efficacy for fixed-dose combination tablets compared to loose non-fixed dose combinations. This highlights the benefits of fixed-dose combinations as a practical strategy for ensuring optimal antimalarial dosing and maximizing efficacy. Please see related article: http://www.biomedcentral.com/1741-7015/13/66.

  5. Topological fixed point theory of multivalued mappings

    CERN Document Server

    Górniewicz, Lech

    1999-01-01

    This volume presents a broad introduction to the topological fixed point theory of multivalued (set-valued) mappings, treating both classical concepts as well as modern techniques. A variety of up-to-date results is described within a unified framework. Topics covered include the basic theory of set-valued mappings with both convex and nonconvex values, approximation and homological methods in the fixed point theory together with a thorough discussion of various index theories for mappings with a topologically complex structure of values, applications to many fields of mathematics, mathematical economics and related subjects, and the fixed point approach to the theory of ordinary differential inclusions. The work emphasises the topological aspect of the theory, and gives special attention to the Lefschetz and Nielsen fixed point theory for acyclic valued mappings with diverse compactness assumptions via graph approximation and the homological approach. Audience: This work will be of interest to researchers an...

  6. HEALTH INSURANCE: FIXED CONTRIBUTION AND REIMBURSEMENT MAXIMA

    CERN Multimedia

    Human Resources Division

    2001-01-01

    Affected by the salary adjustments on 1 January 2001 and the evolution of the staff members and fellows population, the average reference salary, which is used as an index for fixed contributions and reimbursement maxima, has changed significantly. An adjustment of the amounts of the reimbursement maxima and the fixed contributions is therefore necessary, as from 1 January 2001. Reimbursement maxima The revised reimbursement maxima will appear on the leaflet summarizing the benefits for the year 2001, which will be sent out with the forthcoming issue of the CHIS Bull'. This leaflet will also be available from the divisional secretariats and from the UNIQA office at CERN. Fixed contributions The fixed contributions, applicable to some categories of voluntarily insured persons, are set as follows (amounts in CHF for monthly contributions) : voluntarily insured member of the personnel, with normal health insurance cover : 910.- (was 815.- in 2000) voluntarily insured member of the personnel, with reduced heal...

  7. Gauge Fixing on the Lattice without Ambiguity

    CERN Document Server

    Vink, Jeroen C; 10.1016/0370-2693(92)91372-G

    2009-01-01

    A new gauge fixing condition is discussed, which is (lattice) rotation invariant, has the `smoothness' properties of the Landau gauge but can be efficiently computed and is unambiguous for almost all lattice gauge field configurations.

  8. Anderson Acceleration for Fixed-Point Iterations

    Energy Technology Data Exchange (ETDEWEB)

    Walker, Homer F. [Worcester Polytechnic Institute, MA (United States)

    2015-08-31

    The purpose of this grant was to support research on acceleration methods for fixed-point iterations, with applications to computational frameworks and simulation problems that are of interest to DOE.

  9. Global Wilson-Fisher fixed points

    Science.gov (United States)

    Jüttner, Andreas; Litim, Daniel F.; Marchais, Edouard

    2017-08-01

    The Wilson-Fisher fixed point with O (N) universality in three dimensions is studied using the renormalisation group. It is shown how a combination of analytical and numerical techniques determine global fixed points to leading order in the derivative expansion for real or purely imaginary fields with moderate numerical effort. Universal and non-universal quantities such as scaling exponents and mass ratios are computed, for all N, together with local fixed point coordinates, radii of convergence, and parameters which control the asymptotic behaviour of the effective action. We also explain when and why finite-N results do not converge pointwise towards the exact infinite-N limit. In the regime of purely imaginary fields, a new link between singularities of fixed point effective actions and singularities of their counterparts by Polchinski are established. Implications for other theories are indicated.

  10. Fixed-Point Configurable Hardware Components

    Directory of Open Access Journals (Sweden)

    Rocher Romuald

    2006-01-01

    Full Text Available To reduce the gap between the VLSI technology capability and the designer productivity, design reuse based on IP (intellectual properties is commonly used. In terms of arithmetic accuracy, the generated architecture can generally only be configured through the input and output word lengths. In this paper, a new kind of method to optimize fixed-point arithmetic IP has been proposed. The architecture cost is minimized under accuracy constraints defined by the user. Our approach allows exploring the fixed-point search space and the algorithm-level search space to select the optimized structure and fixed-point specification. To significantly reduce the optimization and design times, analytical models are used for the fixed-point optimization process.

  11. Gravitational fixed points from perturbation theory.

    Science.gov (United States)

    Niedermaier, Max R

    2009-09-04

    The fixed point structure of the renormalization flow in higher derivative gravity is investigated in terms of the background covariant effective action using an operator cutoff that keeps track of powerlike divergences. Spectral positivity of the gauge fixed Hessian can be satisfied upon expansion in the asymptotically free higher derivative coupling. At one-loop order in this coupling strictly positive fixed points are found for the dimensionless Newton constant g(N) and the cosmological constant lambda, which are determined solely by the coefficients of the powerlike divergences. The renormalization flow is asymptotically safe with respect to this fixed point and settles on a lambda(g(N)) trajectory after O(10) units of the renormalization mass scale to accuracy 10(-7).

  12. On hyperbolic fixed points in ultrametric dynamics

    CERN Document Server

    Lindahl, Karl-Olof; 10.1134/S2070046610030052

    2011-01-01

    Let K be a complete ultrametric field. We give lower and upper bounds for the size of linearization discs for power series over K near hyperbolic fixed points. These estimates are maximal in the sense that there exist examples where these estimates give the exact size of the corresponding linearization disc. In particular, at repelling fixed points, the linearization disc is equal to the maximal disc on which the power series is injective.

  13. Fractal Structures For Fixed Mems Capacitors

    KAUST Repository

    Elshurafa, Amro M.

    2014-08-28

    An embodiment of a fractal fixed capacitor comprises a capacitor body in a microelectromechanical system (MEMS) structure. The capacitor body has a first plate with a fractal shape separated by a horizontal distance from a second plate with a fractal shape. The first plate and the second plate are within the same plane. Such a fractal fixed capacitor further comprises a substrate above which the capacitor body is positioned.

  14. Cross Service Fixed-Wing Cost Estimation

    Science.gov (United States)

    2016-05-17

    clarify the costing methods for O&S costs for fixed-wing delivery platforms with the intent of extending the research to other cross- service mission costs...proof-of-concept, this project will concentrate on equating equitable cross- service costs for fixed-wing munitions delivery platforms. The method of... delivery is an essential part of the AoA, especially when the project proposed is the replacement of current missile systems. The services have

  15. Random fixed points and random differential inclusions

    Directory of Open Access Journals (Sweden)

    Nikolaos S. Papageorgiou

    1988-01-01

    Full Text Available In this paper, first, we study random best approximations to random sets, using fixed point techniques, obtaining this way stochastic analogues of earlier deterministic results by Browder-Petryshyn, KyFan and Reich. Then we prove two fixed point theorems for random multifunctions with stochastic domain that satisfy certain tangential conditions. Finally we consider a random differential inclusion with upper semicontinuous orientor field and establish the existence of random solutions.

  16. DNA extraction from formalin-fixed material.

    Science.gov (United States)

    Campos, Paula F; Gilbert, Thomas M P

    2012-01-01

    The principal challenges facing PCR-based analyses of DNA extracted from formalin-fixed materials are fragmentation of the DNA and cross-linked protein-DNA complexes. Here, we present an efficient protocol to extract DNA from formalin-fixed or paraffin-embedded tissues (FFPE). In this protocol, protein-DNA cross-links are reversed using heat and alkali treatment, yielding significantly longer fragments and larger amounts of PCR-amplifiable DNA than standard DNA extraction protocols.

  17. Valganciclovir dosing using area under the curve calculations in pediatric solid organ transplant recipients.

    Science.gov (United States)

    Villeneuve, David; Brothers, Adam; Harvey, Eric; Kemna, Mariska; Law, Yuk; Nemeth, Thomas; Gantt, Soren

    2013-02-01

    Pediatric valganciclovir dosing recommendations have not been extensively validated for prevention or treatment for CMV infection. As such, we performed a pharmacokinetic study to compare different valganciclovir dosing regimens and the potential benefits of individualized dose adjustments in children following organ transplantation. Ganciclovir AUCs were calculated from four plasma drug levels in pediatric SOT recipients aged six months through three yr receiving valganciclovir suspension by mouth. Of the 28 ganciclovir AUC calculations performed, 11 (39%) were outside the therapeutic target range of 40-60 mcg h/L leading to a valganciclovir dose adjustment. Current manufacturer-recommended dosing based on BSA and CrCl was estimated to result in therapeutic AUCs in fewer patients than the simple weight-based formula used in our institution (4 vs. 13; p = 0.017). An AUC calculation using only the two- and five-h measurements was strongly correlated with the AUC using all four time measurements (R(2) = 0.846; p < 0.001). A simple weight-based dosing approach gives a higher probability for therapeutic AUCs compared to the manufacturer-recommended dosing in pediatric transplant patients aged six months through three yr with normal renal function. An AUC calculated using two sample times might allow for fewer blood draws in the future. © 2012 John Wiley & Sons A/S.

  18. Precise Point Positioning with Partial Ambiguity Fixing

    Science.gov (United States)

    Li, Pan; Zhang, Xiaohong

    2015-01-01

    Reliable and rapid ambiguity resolution (AR) is the key to fast precise point positioning (PPP). We propose a modified partial ambiguity resolution (PAR) method, in which an elevation and standard deviation criterion are first used to remove the low-precision ambiguity estimates for AR. Subsequently the success rate and ratio-test are simultaneously used in an iterative process to increase the possibility of finding a subset of decorrelated ambiguities which can be fixed with high confidence. One can apply the proposed PAR method to try to achieve an ambiguity-fixed solution when full ambiguity resolution (FAR) fails. We validate this method using data from 450 stations during DOY 021 to 027, 2012. Results demonstrate the proposed PAR method can significantly shorten the time to first fix (TTFF) and increase the fixing rate. Compared with FAR, the average TTFF for PAR is reduced by 14.9% for static PPP and 15.1% for kinematic PPP. Besides, using the PAR method, the average fixing rate can be increased from 83.5% to 98.2% for static PPP, from 80.1% to 95.2% for kinematic PPP respectively. Kinematic PPP accuracy with PAR can also be significantly improved, compared to that with FAR, due to a higher fixing rate. PMID:26067196

  19. A mathematical approach to optimal selection of dose values in the additive dose method of ERP dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Hayes, R.B.; Haskell, E.H.; Kenner, G.H. [Utah Univ., Salt Lake City, UT (United States)

    1996-01-01

    Additive dose methods commonly used in electron paramagnetic resonance (EPR) dosimetry are time consuming and labor intensive. We have developed a mathematical approach for determining optimal spacing of applied doses and the number of spectra which should be taken at each dose level. Expected uncertainitites in the data points are assumed to be normally distributed with a fixed standard deviation and linearity of dose response is also assumed. The optimum spacing and number of points necessary for the minimal error can be estimated, as can the likely error in the resulting estimate. When low doses are being estimated for tooth enamel samples the optimal spacing is shown to be a concentration of points near the zero dose value with fewer spectra taken at a single high dose value within the range of known linearity. Optimization of the analytical process results in increased accuracy and sample throughput.

  20. Should we routinely remove the dose delivered by the images of control?; Faut-il systematiquement retirer la dose delivree par les images de controle?

    Energy Technology Data Exchange (ETDEWEB)

    Goasduff, G. [Centre Hospitalier Universitaire Morvan, Service de Radiotherapie, 29 - Brest (France); Pene Baverez, D.; Pradier, O.; Bouchekoua, M. [Service de Radiotherapie, 29 - Brest (France)

    2009-10-15

    The constraints of doses fixed by the international commission on radiation units and measurements (ICRU) for the target volume (95-107% of the prescribed dose) are respected. for the hypo fractionated treatments, it is necessary to control the impact of the dose delivered by the control images for every patient. The dose delivered at the isocenter is estimated between 1 and 3 Gy by control image: this dose depends on the beams size and on the distance-source-skin. Protocols of the patient positioning checking must be implemented on optimizing their frequency to limit the dose received by the patient. (N.C.)

  1. Effects of three different PAHs on nitrogen-fixing bacterial diversity in mangrove sediment.

    Science.gov (United States)

    Sun, Fu-Lin; Wang, You-Shao; Sun, Cui-Ci; Peng, Ya-Lan; Deng, Chao

    2012-08-01

    Polycyclic aromatic hydrocarbons (PAHs) are of great environmental and human health concerns due to their widespread occurrence, persistence and carcinogenic properties. There is now compelling evidence that the mangrove sediment microbial structure is susceptible to PAHs contamination. The study aimed to assess the effects of PAHs on the nitrogen-fixing bacterial community of mangrove sediment. Three types of PAHs, naphthalene (NAP), a two-ring PAH; fluorene (FLU), a three-ring PAH; and pyrene (PYR), a four-ring PAH; were applied at three doses. After 7 and 24 days of incubation, the nitrogen-fixing bacterial population and diversity were evidenced in the nifH gene polymerase chain reaction denaturing gradient gel electrophoresis profile. DGGE pattern shows that the nitrogen-fixing bacterial community changed significantly with the types and doses of PAHs, and the incubation time. As far as single PAH is concerned, high concentration of PAH has larger impact on the nitrogen-fixing bacteria than low concentration of PAH. Besides, among the three types of PAHs, NAP has the greatest short term toxicity; PYR has the strongest long-term impact, whereas FLU has relatively higher long-time effect. Multidimensional scaling analysis and correspondence analysis are two reliable multivariate analysis methods for investigating the relationship between the nitrogen-fixing bacterial community and PAHs contamination. Investigating the effect of PAHs on the nitrogen-fixing bacterial diversity could yield useful information for understanding the process of biogeochemical cycling of nitrogen in mangrove sediment. The present study reveals that nitrogen-fixing bacterial community can be used as an important parameter indicating the impact of PAHs on mangrove sediment ecosystem.

  2. New patents of fixed combinations of nasal antihistamines and corticosteroids in allergic rhinitis.

    Science.gov (United States)

    Wolthers, Ole D

    2013-09-01

    During the last few years, fixed combinations of intranasal antihistamines and corticosteroids have been introduced for treatment of allergic rhinitis. The aim of this systematic review was to assess recent patents and clinical evidence for fixed combinations of intranasal antihistamines and intranasal corticosteroids in allergic rhinitis. Data base searches revealed that intranasal combinations of the antihistamine azelastine with the corticosteroids mometasone furoate, ciclesonide and fluticasone propionate, respectively, have been patented. Four randomized, double-blinded, parallel-group, placebo-controlled, multicenter trials sponsored by the manufacturer evaluated the fixed combination of intranasal azelastine 125 µg and fluticasone propionate 50 µg administered as one dose per nostril b.i.d. in patients with moderate-to-severe symptomatic allergic rhinitis ≥ 12 years of age. Three of the studies were published as a meta-analysis which found the fixed combination of azelastine and fluticasone propionate statistically significantly more efficacious in reducing baseline total nasal symptom score by 5.7 as compared to azelastine (4.4; P antihistamines and corticosteroids are needed, especially, in primary care settings and in children before fixed combination treatment can be considered first line therapy in allergic rhinitis. Fixed combination treatment of azelastine and fluticasone propionate may offer additional benefit to selected populations of adolescents and adults with moderate-to-severe symptoms.

  3. Fixed points of symplectic periodic flows

    CERN Document Server

    Pelayo, Alvaro

    2010-01-01

    The study of fixed points is a classical subject in geometry and dynamics. If the circle acts in a Hamiltonian fashion on a compact symplectic manifold M, then it is classically known that there are at least 1 + dim(M)/2 fixed points; this follows from Morse theory for the momentum map of the action. In this paper we use Atiyah-Bott-Berline-Vergne (ABBV) localization in equivariant cohomology to prove that this conclusion also holds for symplectic circle actions with non-empty fixed sets, as long as the Chern class map is somewhere injective -- the Chern class map assigns to a fixed point the sum of the action weights at the point. We complement this result with less sharp lower bounds on the number of fixed points, under no assumptions; from a dynamical systems viewpoint, our results imply that there is no symplectic periodic flow with exactly one or two equilibrium points on a compact manifold of dimension at least eight.

  4. Inadvertent tooth movement with fixed lingual retainers.

    Science.gov (United States)

    Shaughnessy, Timothy G; Proffit, William R; Samara, Said A

    2016-02-01

    Fixed retainers are effective in maintaining the alignment of the anterior teeth more than 90% of the time, but they can produce inadvertent tooth movement that in the most severe instances requires orthodontic retreatment managed with a periodontist. This is different from relapse into crowding when a fixed retainer is lost. These problems arise when the retainer breaks but remains bonded to some or all teeth, or when an intact retainer is distorted by function or was not passive when bonded. In both instances, torque of the affected teeth is the predominant outcome. A fixed retainer made with dead soft wire is the least likely to create torque problems but is the most likely to break. Highly flexible twist wires bonded to all the teeth appear to be the most likely to produce inadvertent tooth movement, but this also can occur with stiffer wires bonded only to the canines. Orthodontists, general dentists, and patients should be aware of possible problems with fixed retainers, especially those with all teeth bonded, because the patient might not notice partial debonding. Regular observations of patients wearing fixed retainers by orthodontists in the short term and family dentists in the long term are needed.

  5. The computation of fixed points and applications

    CERN Document Server

    Todd, Michael J

    1976-01-01

    Fixed-point algorithms have diverse applications in economics, optimization, game theory and the numerical solution of boundary-value problems. Since Scarf's pioneering work [56,57] on obtaining approximate fixed points of continuous mappings, a great deal of research has been done in extending the applicability and improving the efficiency of fixed-point methods. Much of this work is available only in research papers, although Scarf's book [58] gives a remarkably clear exposition of the power of fixed-point methods. However, the algorithms described by Scarf have been super~eded by the more sophisticated restart and homotopy techniques of Merrill [~8,~9] and Eaves and Saigal [1~,16]. To understand the more efficient algorithms one must become familiar with the notions of triangulation and simplicial approxi- tion, whereas Scarf stresses the concept of primitive set. These notes are intended to introduce to a wider audience the most recent fixed-point methods and their applications. Our approach is therefore ...

  6. Au Fixed Point Development at NRC

    Science.gov (United States)

    Dedyulin, S. N.; Gotoh, M.; Todd, A. D. W.

    2017-04-01

    Two Au fixed points filled using metal of different nominal purities in carbon crucibles have been developed at the National Research Council Canada (NRC). The primary motivation behind this project was to provide the means for direct thermocouple calibrations at the Au freezing point (1064.18°C). Using a Au fixed point filled with the metal of maximum available purity [99.9997 % pure according to glow discharge mass spectroscopy (GDMS)], multiple freezing plateaus were measured in a commercial high-temperature furnace. Four Pt/Pd thermocouples constructed and calibrated in-house were used to measure the freezing plateaus. From the calibration at Sn, Zn, Al and Ag fixed points, the linear deviation function from the NIST-IMGC reference function (IEC 62460:2008 Standard) was determined and extrapolated to the freezing temperature of Au. For all the Pt/Pd thermocouples used in this study, the measured EMF values agree with the extrapolated values within expanded uncertainty, thus substantiating the use of 99.9997 % pure Au fixed point cell for thermocouple calibrations at NRC. Using the Au fixed point filled with metal of lower purity (99.99 % pure according to GDMS), the effect of impurities on the Au freezing temperature measured with Pt/Pd thermocouple was further investigated.

  7. Fixed point theory in metric type spaces

    CERN Document Server

    Agarwal, Ravi P; O’Regan, Donal; Roldán-López-de-Hierro, Antonio Francisco

    2015-01-01

    Written by a team of leading experts in the field, this volume presents a self-contained account of the theory, techniques and results in metric type spaces (in particular in G-metric spaces); that is, the text approaches this important area of fixed point analysis beginning from the basic ideas of metric space topology. The text is structured so that it leads the reader from preliminaries and historical notes on metric spaces (in particular G-metric spaces) and on mappings, to Banach type contraction theorems in metric type spaces, fixed point theory in partially ordered G-metric spaces, fixed point theory for expansive mappings in metric type spaces, generalizations, present results and techniques in a very general abstract setting and framework. Fixed point theory is one of the major research areas in nonlinear analysis. This is partly due to the fact that in many real world problems fixed point theory is the basic mathematical tool used to establish the existence of solutions to problems which arise natur...

  8. Fixed target facility at the SSC

    Energy Technology Data Exchange (ETDEWEB)

    Loken, S.C.; Morfin, J.G.

    1985-01-01

    The question of whether a facility for fixed target physics should be provided at the SSC must be answered before the final technical design of the SSC can be completed, particularly if the eventual form of extraction would influence the magnet design. To this end, an enthusiastic group of experimentalists, theoreticians and accelerator specialists have studied this point. The accelerator physics issues were addressed by a group led by E. Colton whose report is contained in these proceedings. The physics addressable by fixed target was considered by many of the Physics area working groups and in particular by the Structure Function Group. This report is the summary of the working group which considered various SSC fixed target experiments and determined which types of beams and detectors would be required. 13 references, 5 figures.

  9. Fixed point theory of parametrized equivariant maps

    CERN Document Server

    Ulrich, Hanno

    1988-01-01

    The first part of this research monograph discusses general properties of G-ENRBs - Euclidean Neighbourhood Retracts over B with action of a compact Lie group G - and their relations with fibrations, continuous submersions, and fibre bundles. It thus addresses equivariant point set topology as well as equivariant homotopy theory. Notable tools are vertical Jaworowski criterion and an equivariant transversality theorem. The second part presents equivariant cohomology theory showing that equivariant fixed point theory is isomorphic to equivariant stable cohomotopy theory. A crucial result is the sum decomposition of the equivariant fixed point index which provides an insight into the structure of the theory's coefficient group. Among the consequences of the sum formula are some Borsuk-Ulam theorems as well as some folklore results on compact Lie-groups. The final section investigates the fixed point index in equivariant K-theory. The book is intended to be a thorough and comprehensive presentation of its subjec...

  10. Fix og færdig

    Directory of Open Access Journals (Sweden)

    Jens Pedersen

    2012-12-01

    Full Text Available Fix & Finish “WHO CAN FIX IT?” is an investigation of the needles left behind by drug users in Copenhagen’s Vesterbro district. Based on the praxiological methods developed by Annemarie Mol as well as processes of objectification as described by Daniel Miller, the used needle appears to be a multiple object that is related to opportunities, fear, good intentions and trash. This article is an invitation to study material culture and material practices as a part of semiotic and discursive analyses in order to sharpen a researcher’s analytical focus while remaining grounded in reality.

  11. Duan's fixed point theorem: Proof and generalization

    Directory of Open Access Journals (Sweden)

    Arkowitz Martin

    2006-01-01

    Full Text Available Let be an H-space of the homotopy type of a connected, finite CW-complex, any map and the th power map. Duan proved that has a fixed point if . We give a new, short and elementary proof of this. We then use rational homotopy to generalize to spaces whose rational cohomology is the tensor product of an exterior algebra on odd dimensional generators with the tensor product of truncated polynomial algebras on even dimensional generators. The role of the power map is played by a -structure as defined by Hemmi-Morisugi-Ooshima. The conclusion is that and each has a fixed point.

  12. Fixed export cost heterogeneity, trade and welfare

    DEFF Research Database (Denmark)

    Jørgensen, Jan Guldager; Schröder, Philipp J.H.

    2008-01-01

    -country intra-industry trade model where firms are of two different marginal costs types and where fixed export costs are heterogeneous across firms. This model traces many of the stylized facts of international trade. However, we find that with heterogeneous fixed export costs there exists a positive bilateral......Recent literature on the workhorse model of intra-industry trade has explored heterogeneous cost structures at the firm level. These approaches have proven to add realism and predictive power. This paper presents a new and simple heterogeneous-firms specification. We develop a symmetric two...

  13. Fixed and variable cost of automobiles

    DEFF Research Database (Denmark)

    Mulalic, Ismir; Rouwendal, Jan

    Recent empirical analyses have found strong reactions of car prices to changes in fuel costs. We develop a model of car quality choice to further investigate this relationship. We show that in the empirically relevant case quality characteristics increase fixed as well as variable costs, and our...... model focuses on that situation. Quality aspects must then be an argument of the utility function and we introduce them in a general way. In equilibrium the marginal willingness to pay for these aspects must be equal to their margi nal impact on fixed as well as variable costs. We estimate the marginal...

  14. General Common Fixed Point Theorems and Applications

    Directory of Open Access Journals (Sweden)

    Shyam Lal Singh

    2012-01-01

    Full Text Available The main result is a common fixed point theorem for a pair of multivalued maps on a complete metric space extending a recent result of Đorić and Lazović (2011 for a multivalued map on a metric space satisfying Ćirić-Suzuki-type-generalized contraction. Further, as a special case, we obtain a generalization of an important common fixed point theorem of Ćirić (1974. Existence of a common solution for a class of functional equations arising in dynamic programming is also discussed.

  15. Fixed Wordsize Implementation of Lifting Schemes

    Science.gov (United States)

    Karp, Tanja

    2006-12-01

    We present a reversible nonlinear discrete wavelet transform with predefined fixed wordsize based on lifting schemes. Restricting the dynamic range of the wavelet domain coefficients due to a fixed wordsize may result in overflow. We show how this overflow has to be handled in order to maintain reversibility of the transform. We also perform an analysis on how large a wordsize of the wavelet coefficients is needed to perform optimal lossless and lossy compressions of images. The scheme is advantageous to well-known integer-to-integer transforms since the wordsize of adders and multipliers can be predefined and does not increase steadily. This also results in significant gains in hardware implementations.

  16. Carbon-Fixing Reactions of Photosynthesis.

    Science.gov (United States)

    2016-07-01

    Summaryplantcell;28/7/tpc.116.tt0716/FIG1F1fig1Photosynthesis in plants converts the energy of sunlight into chemical energy. Although photosynthesis involves many proteins and catalytic processes, it often is described as two sets of reactions, the light-dependent reactions and the carbon-fixing reactions. This lesson introduces the core biochemistry of the carbon-fixing reactions of photosynthesis, as well as its variations, C4 and CAM. Finally, it addresses how and why plants are affected by rising atmospheric CO2 levels, and research efforts to increase photosynthetic efficiency in current and future conditions. © 2016 American Society of Plant Biologists. All rights reserved.

  17. Recurrent fixed drug eruption caused by citiolone.

    Science.gov (United States)

    de Barrio, M; Tornero, P; Prieto, A; Sainza, T; Zubeldia, J M; Herrero, T

    1997-01-01

    Citiolone (N-acetylhomocysteinethiolactone) is a thiolic-derived medication frequently used in Spain and in other countries as a mucolytic agent for the treatment of certain hepatic disorders. Mucolytic drugs have rarely been implicated in the fixed drug eruption etiology. We report on a patient who presented several episodes of fixed exanthema related to citiolone intake. The patch test with citiolone (10% in dimethyl sulfoxide) was negative. The diagnosis was confirmed by a positive controlled oral challenge test. Other mucolytic thiolic-derivatives (N-acetylcysteine) were tolerated by the patient, thus crossreactivity between these drugs seems to be unlikely.

  18. Dose mapping of dried figs treated by gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Polonia, I.; Portugal, L.; Andrade, M. E

    1998-06-01

    The irradiation parameters of two varieties of dried figs were determined in a fixed position. The Dose Uniformity (U=Dmax/Dmin) obtained for Fricke Dosimeter was 1.4 and for YR Gammachrome 1.3. The isodose curves were built using a geostatistical gridding method, the Kriging method.

  19. Fixed Drug Eruption in an Epileptic Patient Previously Receiving Treatment With Phenytoin for Seven Years

    Directory of Open Access Journals (Sweden)

    Keaton S. Smetana

    2013-11-01

    Full Text Available A 52-year-old African American female presented with severe left thigh pain of unknown etiology. She had a past medical history of generalized seizure disorder treated with phenytoin for 7 years without incident. During admission a nurse witnessed a seizure, and consequently loading and maintenance doses of phenytoin were administered to obtain a therapeutic serum concentration. The patient had a history of noncompliance with multiple subtherapeutic phenytoin levels. Subsequently, unifocal blue discolored spots appeared, progressing to a bullous component that was positive for skin sloughing. Drug-induced fixed drug eruption was diagnosed and attributed to phenytoin. Clinicians should be cognizant of drug-induced fixed drug eruption in patients just initiated and those receiving long-term treatment with phenytoin. The administration rate of phenytoin may be associated with the development of fixed drug eruption.

  20. Unfractionated heparin dosing for venous thromboembolism in morbidly obese patients: case report and review of the literature.

    Science.gov (United States)

    Myzienski, April E; Lutz, Mark F; Smythe, Maureen A

    2010-03-01

    Unfractionated heparin infusion therapy is often administered using a weight-based dosing strategy for the treatment of venous thromboembolism. In the last several decades, the prevalence of obesity in the United States has increased significantly. The applicability of weight-based heparin dosing recommendations in the obese and morbidly obese population is uncertain, as limited data are available. We describe a 388-kg man who was started on an intravenous infusion of heparin according to hospital protocol for suspected pulmonary embolism. The patient was given a 5000-unit heparin bolus followed by an initial heparin infusion rate of 1500 units/hour, the maximum initial rate specified in the protocol. After additional infusion rate adjustments, a therapeutic activated partial thromboplastin time (aPTT) was reached 55 hours later with a heparin infusion rate of 3650 units/hour. Due to concerns of heparin-induced thrombocytopenia, heparin therapy was discontinued, and fondaparinux 5 mg/day was started. However, heparin therapy was restarted 4 days later for persistent, refractory hypoxemia and recurrent concerns of possible pulmonary embolism. During this second course, a therapeutic aPTT was achieved with a heparin infusion rate of 3550 units/hour. The patient developed bloody pulmonary secretions (with a therapeutic aPTT), necessitating the discontinuation of the heparin infusion. The patient later died after developing pulseless electrical activity. Standard weight-based heparin dosing protocols that specify maximum doses for initial bolus and infusion rates can result in significant delays in time to achieve therapeutic anticoagulation in the obese and morbidly obese patient. Despite limited data on heparin dosing in obesity, we recommend the use of a dosing weight to determine initial heparin dosing when treating venous thromboembolism in morbidly obese patients. It is reasonable to consider one of the following formulas: dosing weight = ideal body weight (IBW

  1. Investigating quartz optically stimulated luminescence dose-response curves at high doses

    Energy Technology Data Exchange (ETDEWEB)

    Lowick, Sally E., E-mail: lowick@geo.unibe.c [Institut fuer Geologie, Universitaet Bern, Baltzerstrasse 1-3, 3012 Bern (Switzerland); Preusser, Frank [Institut fuer Geologie, Universitaet Bern, Baltzerstrasse 1-3, 3012 Bern (Switzerland); Wintle, Ann G. [Institute of Geography and Earth Sciences, Aberystwyth University, AberystwythSY23 3DB (United Kingdom)

    2010-10-15

    Despite the general expectation that optically stimulated luminescence (OSL) growth should be described by a simple saturating exponential function, an additional high dose component is often reported in the dose response of quartz. Although often reported as linear, it appears that this response is the early expression of a second saturating exponential. While some studies using equivalent doses that fall in this high dose region have produced ages that correlate well with independent dating, others report that it results in unreliable age determinations. Two fine grain sedimentary quartz samples that display such a response were used to investigate the origin of this additional high dose component: three experiments were conducted to examine their dose-response up to >1000 Gy. The high dose rates provided by laboratory irradiation were found not to induce a sensitivity change in the response to a subsequent test dose, with the latter not being significantly different from those generated following naturally acquired doses. The relative percentage contributions of the fast and medium OSL components remained fixed throughout the dose-response curve, suggesting that the electron traps that give rise to the initial OSL do not change with dose. An attempt was made to investigate a change in luminescence centre recombination probability by monitoring the depletion of the '325 {sup o}C' thermoluminescence (TL) during the optical stimulation that would result in depletion of the OSL signal. The emissions measured through both the conventional ultraviolet (UV), and a longer wavelength violet/blue (VB) window, displayed similar relative growth with dose, although it was not possible to resolve the origin of the VB emissions. No evidence was found to indicate whether the additional component at high doses occurs naturally or is a product of laboratory treatment. However, it appears that these samples display an increased sensitivity of quartz OSL to high doses

  2. Development of Real-Time Measurement of Effective Dose for High Dose Rate Neutron Fields

    CERN Document Server

    Braby, L A; Reece, W D

    2003-01-01

    Studies of the effects of low doses of ionizing radiation require sources of radiation which are well characterized in terms of the dose and the quality of the radiation. One of the best measures of the quality of neutron irradiation is the dose mean lineal energy. At very low dose rates this can be determined by measuring individual energy deposition events, and calculating the dose mean of the event size. However, at the dose rates that are normally required for biology experiments, the individual events can not be separated by radiation detectors. However, the total energy deposited in a specified time interval can be measured. This total energy has a random variation which depends on the size of the individual events, so the dose mean lineal energy can be calculated from the variance of repeated measurements of the energy deposited in a fixed time. We have developed a specialized charge integration circuit for the measurement of the charge produced in a small ion chamber in typical neutron irradiation exp...

  3. Stress tolerant crops from nitrogen fixing trees

    Energy Technology Data Exchange (ETDEWEB)

    Becker, R.; Saunders, R.M.

    1983-01-01

    Notes are given on the nutritional quality and uses of: pods of Geoffroea decorticans, a species tolerant of saline and limed soils and saline water; seeds of Olneya tesota which nodulates readily and fixes nitrogen and photosynthesizes at low water potential; and pods of Prosopis chilensis and P. tamarugo which tolerate long periods without rain. 3 references.

  4. Untangling Fixed Effects and Constant Regressors

    NARCIS (Netherlands)

    Klaassen, F.; Teulings, R.

    2015-01-01

    Fixed effects (FE) in panel data models overlap each other and prohibit the identification of the impact of "constant" regressors. Think of regressors that are constant across countries in a country-time panel with time FE. The traditional approach is to drop some FE and constant regressors by

  5. Tunnel Diode Discriminator with Fixed Dead Time

    DEFF Research Database (Denmark)

    Diamond, J. M.

    1965-01-01

    A solid state discriminator for the range 0.4 to 10 V is described. Tunnel diodes are used for the discriminator element and in a special fixed dead time circuit. An analysis of temperature stability is presented. The regulated power supplies are described, including a special negative resistance...

  6. Fixing the Shadows While Moving the Gnomon

    Science.gov (United States)

    Gangui, Alejandro

    2015-01-01

    It is a common practice to fix a vertical gnomon and study the moving shadow cast by it. This shows our local solar time and gives us a hint regarding the season in which we perform the observation. The moving shadow can also tell us our latitude with high precision. In this paper we propose to exchange the roles and while keeping the shadows…

  7. Simplicial fixed point algorithms and applications

    NARCIS (Netherlands)

    Yang, Z.F.

    1996-01-01

    Fixed point theory is an important branch of modern mathematics and has always been a major theoretical tool in fields such as differential equations, topology, function analysis, optimal control, economics, and game theory. Its applicability has been increased enormously by the development of

  8. Empirical Studies on Sovereign Fixed Income Markets

    NARCIS (Netherlands)

    J.G. Duyvesteyn (Johan)

    2015-01-01

    markdownabstractAbstract This dissertation presents evidence of five studies showing that sovereign fixed income markets are not always price efficient. The emerging local currency debt market has grown to a large size of more than 1.5 trill ion US Dollars at the end of 2012. The factors

  9. Common Fixed Points for Weakly Compatible Maps

    Indian Academy of Sciences (India)

    Renu Chugh; Sanjay Kumar

    2001-05-01

    The purpose of this paper is to prove a common fixed point theorem, from the class of compatible continuous maps to a larger class of maps having weakly compatible maps without appeal to continuity, which generalized the results of Jungck [3], Fisher [1], Kang and Kim [8], Jachymski [2], and Rhoades [9].

  10. A New Fixed Point Theorem and Applications

    Directory of Open Access Journals (Sweden)

    Min Fang

    2013-01-01

    Full Text Available A new fixed point theorem is established under the setting of a generalized finitely continuous topological space (GFC-space without the convexity structure. As applications, a weak KKM theorem and a minimax inequalities of Ky Fan type are also obtained under suitable conditions. Our results are different from known results in the literature.

  11. A Dynamical Approach to Gauge Fixing

    CERN Document Server

    Loran, F

    2002-01-01

    We study gauge fixing in the generalized Gupta-Bleuler quantization. In this method physical states are defined to be simultaneous null eigenstates of a set of quantum invariants. We apply the method to a solvable model proposed by Friedberg, Lee, Pang and Ren and show that no Gribov-type copies appears by construction.

  12. Some Generalizations of Jungck's Fixed Point Theorem

    Directory of Open Access Journals (Sweden)

    J. R. Morales

    2012-01-01

    Full Text Available We are going to generalize the Jungck's fixed point theorem for commuting mappings by mean of the concepts of altering distance functions and compatible pair of mappings, as well as, by using contractive inequalities of integral type and contractive inequalities depending on another function.

  13. Fixed Point Theorems for Asymptotically Contractive Multimappings

    Directory of Open Access Journals (Sweden)

    M. Djedidi

    2012-01-01

    Full Text Available We present fixed point theorems for a nonexpansive set-valued mapping from a closed convex subset of a reflexive Banach space into itself under some asymptotic contraction assumptions. Some existence results of coincidence points and eigenvalues for multimappings are given.

  14. Generalized Common Fixed Point Results with Applications

    Directory of Open Access Journals (Sweden)

    Marwan Amin Kutbi

    2014-01-01

    Full Text Available We obtained some generalized common fixed point results in the context of complex valued metric spaces. Moreover, we proved an existence theorem for the common solution for two Urysohn integral equations. Examples are presented to support our results.

  15. Force dynamics in fixed-ratio schedules.

    Science.gov (United States)

    Pinkston, Jonathan W; McBee, Lindsey N

    2014-03-01

    Fixed-ratio schedules are widely used in behavioral research. Although fixed-ratio schedules often conjure up relationships to work and effort, little is known about effort-related measures in these schedules. Early research had shown that force and effort of operant behavior vary systematically during the execution of ratio schedules, and the goal of the present study was to revisit early research on force dynamics in fixed-ratio schedules. Four rats earned sucrose by pressing an isometric force transducer. Presses produced sucrose after ten or twenty responses. In general, the force of responses increased then decreased systematically across the ratio. The possibility that decreases in force during ratio execution was due to a trade-off with the differential reinforcement of short inter-response times (IRT) was investigated in an additional condition where sucrose was made available according to a tandem fixed-ratio 19 inter-response (IRT)> t schedule. The tandem IRT requirement did not eliminate decreasing trends in force across the ratio; unexpectedly, the tandem requirement did eliminate increases in force early in the ratio, which may reflect sequence-level organization operating in the control of force dynamics.

  16. Efficient Fixed-Offset GPR Scattering Analysis

    DEFF Research Database (Denmark)

    Meincke, Peter; Chen, Xianyao

    2004-01-01

    in the scattering calculation the correct radiation patterns of the ground penetrating radar antennas by using their plane-wave transmitting and receiving spectra. Finally, we derive an efficient FFT-based method to analyze a fixed-offset configuration in which the location of the transmitting antenna is different...

  17. Uniqueness of entire functions and fixed points

    OpenAIRE

    Chang, Jianming; Fang, Mingliang

    2002-01-01

    Let $f$ be a nonconstant entire function. %If $f(z)=z$ $\\Longleftrightarrow $ $f'(z)=z$, and %$f'(z)=z$ $\\Longrightarrow $ $f''(z)=z$, then $f\\equiv f'$. In particular, If $f$, $f'$ and $f''$ have the same fixed points, then $f\\equiv f'.$

  18. Untangling Fixed Effects and Constant Regressors

    NARCIS (Netherlands)

    Klaassen, F.; Teulings, R.

    2015-01-01

    Fixed effects (FE) in panel data models overlap each other and prohibit the identification of the impact of "constant" regressors. Think of regressors that are constant across countries in a country-time panel with time FE. The traditional approach is to drop some FE and constant regressors by norma

  19. 29 CFR 1910.27 - Fixed ladders.

    Science.gov (United States)

    2010-07-01

    .... (v) The rungs of an individual-rung ladder shall be so designed that the foot cannot slide off the... OCCUPATIONAL SAFETY AND HEALTH STANDARDS Walking-Working Surfaces § 1910.27 Fixed ladders. (a) Design requirements—(1) Design considerations. All ladders, appurtenances, and fastenings shall be designed to...

  20. Simplicial fixed point algorithms and applications

    NARCIS (Netherlands)

    Yang, Z.F.

    1996-01-01

    Fixed point theory is an important branch of modern mathematics and has always been a major theoretical tool in fields such as differential equations, topology, function analysis, optimal control, economics, and game theory. Its applicability has been increased enormously by the development of simpl

  1. Empirical Studies on Sovereign Fixed Income Markets

    NARCIS (Netherlands)

    J.G. Duyvesteyn (Johan)

    2015-01-01

    markdownabstractAbstract This dissertation presents evidence of five studies showing that sovereign fixed income markets are not always price efficient. The emerging local currency debt market has grown to a large size of more than 1.5 trill ion US Dollars at the end of 2012. The factors that

  2. Uniqueness of entire functions and fixed points

    OpenAIRE

    Chang, Jianming; Fang, Mingliang

    2002-01-01

    Let $f$ be a nonconstant entire function. %If $f(z)=z$ $\\Longleftrightarrow $ $f'(z)=z$, and %$f'(z)=z$ $\\Longrightarrow $ $f''(z)=z$, then $f\\equiv f'$. In particular, If $f$, $f'$ and $f''$ have the same fixed points, then $f\\equiv f'.$

  3. Fixed points and self-reference

    Directory of Open Access Journals (Sweden)

    Raymond M. Smullyan

    1984-01-01

    Full Text Available It is shown how Gödel's famous diagonal argument and a generalization of the recursion theorem are derivable from a common construation. The abstract fixed point theorem of this article is independent of both metamathematics and recursion theory and is perfectly comprehensible to the non-specialist.

  4. Interactive Inconsistency Fixing in Feature Modeling

    Institute of Scientific and Technical Information of China (English)

    王波; 熊英飞; 胡振江; 赵海燕; 张伟; 梅宏

    2014-01-01

    Feature models have been widely adopted to reuse the requirements of a set of similar products in a domain. In feature models’ construction, one basic task is to ensure the consistency of feature models, which often involves detecting and fixing of inconsistencies in feature models. While many approaches have been proposed, most of them focus on detecting inconsistencies rather than fixing inconsistencies. In this paper, we propose a novel dynamic-priority based approach to interactively fixing inconsistencies in feature models, and report an implementation of a system that not only automatically recommends a solution to fixing inconsistencies but also supports domain analysts to gradually reach the desirable solution by dynamically adjusting priorities of constraints. The key technical contribution is, as far as we are aware, the first application of the constraint hierarchy theory to feature modeling, where the degree of domain analysts’ confidence on constraints is expressed by using priority and inconsistencies are resolved by deleting one or more lower-priority constraints. Two case studies demonstrate the usability and scalability (effciency) of our new approach.

  5. Evaluation of the effective dose and image quality of low-dose multi-detector CT for orthodontic treatment planning

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Gi Chung; Han, Won Jeong; Kim, Eun Kyung [Department of Oral and Maxillofacial Radiology, School of Dentistry, Dankook University, Cheonan (Korea, Republic of)

    2010-03-15

    This study was designed to compare the effective doses from low-dose and standard-dose multi-detector CT (MDCT) scanning protocols and evaluate the image quality and the spatial resolution of the low-dose MDCT protocols for clinical use. 6-channel MDCT scanner (Siemens Medical System, Forschheim, Germany), was used for this study. Protocol of the standard-dose MDCT for the orthodontic analysis was 130 kV, 35 mAs, 1.25 mm slice width, 0.8 pitch. Those of the low-dose MDCT for orthodontic analysis and orthodontic surgery were 110 kV, 30 mAs, 1.25 mm slice width, 0.85 pitch and 110 kV, 45 mAs, 2.5 mm slice width, 0.85 pitch. Thermoluminescent dosimeters (TLDs) were placed at 31 sites throughout the levels of adult female ART head and neck phantom. Effective doses were calculated according to ICRP 1990 and 2007 recommendations. A formalin-fixed cadaver and AAPM CT performance phantom were scanned for the evaluation of subjective image quality and spatial resolution. Effective doses in {mu}Sv (E2007) were 699.1, 429.4 and 603.1 for standard-dose CT of orthodontic treatment, low-dose CT of orthodontic analysis, and low-dose CT of orthodontic surgery, respectively. The image quality from the low-dose protocol were not worse than those from the standard-dose protocol. The spatial resolutions of both standard-dose and low-dose CT images were acceptable. From the above results, it can be concluded that the low-dose MDCT protocol is preferable in obtaining CT images for orthodontic analysis and orthodontic surgery.

  6. 46 CFR 184.410 - Electronic position fixing devices.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Electronic position fixing devices. 184.410 Section 184... Electronic position fixing devices. A vessel on an oceans route must be equipped with an electronic position fixing device, capable of providing accurate fixes for the area in which the vessel operates, to...

  7. 46 CFR 28.260 - Electronic position fixing devices.

    Science.gov (United States)

    2010-10-01

    ... Trade § 28.260 Electronic position fixing devices. Each vessel 79 feet (24 meters) or more in length must be equipped with an electronic position fixing device capable of providing accurate fixes for the... 46 Shipping 1 2010-10-01 2010-10-01 false Electronic position fixing devices. 28.260 Section...

  8. 46 CFR 118.410 - Fixed gas fire extinguishing systems.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Fixed gas fire extinguishing systems. 118.410 Section... PROTECTION EQUIPMENT Fixed Fire Extinguishing and Detecting Systems § 118.410 Fixed gas fire extinguishing systems. (a) General. (1) A fixed gas fire extinguishing system aboard a vessel must be approved by...

  9. 46 CFR 181.410 - Fixed gas fire extinguishing systems.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Fixed gas fire extinguishing systems. 181.410 Section... Fixed gas fire extinguishing systems. (a) General. (1) A fixed gas fire extinguishing system aboard a... approved for the system by the Commandant. (4) A fixed gas fire extinguishing system may protect more...

  10. Effects of fixed or self-titrated dosages of Sativex on cannabis withdrawal and cravings.

    Science.gov (United States)

    Trigo, Jose M; Lagzdins, Dina; Rehm, Jürgen; Selby, Peter; Gamaleddin, Islam; Fischer, Benedikt; Barnes, Allan J; Huestis, Marilyn A; Le Foll, Bernard

    2016-04-01

    There is currently no pharmacological treatment approved for cannabis dependence. In this proof of concept study, we assessed the feasibility/effects of fixed and self-titrated dosages of Sativex (1:1, Δ(9)-tetrahydrocannabinol (THC)/cannabidiol (CBD)) on craving and withdrawal from cannabis among nine community-recruited cannabis-dependent subjects. Participants underwent an 8-week double-blind placebo-controlled trial (an ABACADAE design), with four smoke as usual conditions (SAU) (A) separated by four cannabis abstinence conditions (B-E), with administration of either self-titrated/fixed doses of placebo or Sativex (up to 108 mg THC/100 mg CBD). The order of medication administration during abstinence conditions was randomized and counterbalanced. Withdrawal symptoms and craving were assessed using the Cannabis Withdrawal Scale (CWS), Marijuana Withdrawal Checklist (MWC) and Marijuana Craving Questionnaire (MCQ). Medication use was assessed during the study by means of self-reports, vial weight control, toxicology and metabolite analysis. Cannabis use was assessed by means of self-reports. High fixed doses of Sativex were well tolerated and significantly reduced cannabis withdrawal during abstinence, but not craving, as compared to placebo. Self-titrated doses were lower and showed limited efficacy as compared to high fixed doses. Participants reported a significantly lower "high" following Sativex or placebo as compared to SAU conditions. Cannabis/medication use along the study, as per self-reports, suggests compliance with the study conditions. The results found in this proof of concept study warrant further systematic exploration of Sativex as a treatment option for cannabis withdrawal and dependence. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Fixed-phase vs fixed-node quantum Monte Carlo with local and nonlocal interactions

    Science.gov (United States)

    Mitas, Lubos; Melton, Cody

    We study several systems that can be formulated in the fixed-phase and/or fixed-node framework in quantum Monte Carlo calculations. In particular, we try to understand the differences between the biases caused by these approximations that result from using complex vs real trial wave functions. One system is a model that enables us to construct systematically the same type of nodal errors in both real and complex formalism. The errors are comparably similar whenever trial functions are correspondingly accurate. Another aspect of the fixed-phase vs fixed-node approximations is studied for systems with nonlocal operators such as with pseudopotentials and/or spin-orbit effects. We specify how to obtain variational formulation for complex wave functions and nonlocal operators in a manner analogous to the fixed-node calculations with T-moves algorithm. In particular, we show that the fixed-phase/fixed-node is the primary condition for proving that the upper bound property holds.

  12. ANALYTICAL SOLUTION FOR FIXED-FIXED ANISOTROPIC BEAM SUBJECTED TO UNIFORM LOAD

    Institute of Scientific and Technical Information of China (English)

    DING Hao-jiang; HUANG De-jin; WANG Hui-ming

    2006-01-01

    The analytical solutions of the stresses and displacements were obtained for fixed-fixed anisotropic beams subjected to uniform load. A stress function involving unknown coefficients was constructed, and the general expressions of stress and displacement were obtained by means of Airy stress function method. Two types of the description for the fixed end boundary condition were considered. The introduced unknown coefficients in stress function were determined by using the boundary conditions. The analytical solutions for stresses and displacements were finally obtained. Numerical tests show that the analytical solutions agree with the FEM results. The analytical solution supplies a classical example for the elasticity theory.

  13. Fixed-dose combinations in type 2 diabetes – role of the canagliflozin metformin combination

    OpenAIRE

    Fleming JW; Fleming LW; Davis CS

    2015-01-01

    Joshua W Fleming, Laurie W Fleming, Courtney S Davis Department of Pharmacy Practice, The University of Mississippi School of Pharmacy, Jackson, MS, USA Abstract: Canagliflozin–metformin is one of the newest combination therapies available for the treatment of type 2 diabetes mellitus (T2DM). Canagliflozin is an inhibitor of the sodium–glucose co-transporter 2 which causes an increase in the urinary excretion of glucose. In the present article, we review the safety and ef...

  14. Fixed-dose versus separate drug combinations for antihypertensive treatment: literature review

    OpenAIRE

    José Luis Calleja Rivero

    2016-01-01

    Resumen INTRODUCCIÓN La hipertensión arterial requiere de intervenciones efectivas para reducir la morbimortalidad cardiovascular. Las terapias farmacológicas han logrado alcanzar cifras óptimas de presión arterial en los afectados. En las guías clínicas recientes se sugiere la utilización de las combinaciones de medicamentos, esto ha llevado a elaborar una diversidad de combinaciones a dosis fija. OBJETIVO Buscar la mejor evidencia bibliográfica disponible sobre la efectividad d...

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

    NARCIS (Netherlands)

    Pergolizzi Jr., Joseph V.; Laar, van de 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

  16. Fixed dose combination of arterolane and piperaquine: a newer prospect in antimalarial therapy.

    Science.gov (United States)

    Patil, Cy; Katare, Ss; Baig, Ms; Doifode, Sm

    2014-07-01

    Malaria has been very prevalent vector-borne disease in India and until date bears enormous implications on health care services of the country. Over the period of time, the development of resistance to traditional antimalarials like chloroquine has been posed as major deterrent in efforts of malaria control. As the drug resistance is today universally prevalent, especially in Plasmodium falciparum species, major burden of malarial control resides with the new artemisinin drug class. However, arterolane is one of the first fully synthetic non-artemisinin antimalarial compound with rapid schizontocidal activity, hence offering an alternative to artemisinin drugs in malaria control. Piperaquine is a synthetic bisquinoline (4-amioquinoline Antimalarial) with slow and longer schizontocidal activity. Therefore their combination has been shown to provide rapid parasitemic clearance and quick relief of most malaria-related symptoms along with prevention of recrudescences. This combination was approved by Drugs Controller General of India in 2011 for treatment of uncomplicated P. falciparum malaria. The article is aimed at to review this newer prospect in antimalarial therapy for which comprehensive database search was done in Google, Google Scholar, PubMed using the terms "Malaria," "Arterolane," "OZ277," "Piperaquine," and "Artemisinin combination therapy." A total of 323 articles were screened and 28 articles were considered for this review along with the World Health Organization and National malarial program guidelines.

  17. SIMULTANEOUS ESTIMATION OF VALSARTAN AND HYDROCHLOROTHIAZIDE IN FIXED DOSE COMBINATION IN UV SPECTROPHOTOMETRY

    Directory of Open Access Journals (Sweden)

    M. M. Deshpande et al.

    2012-01-01

    Full Text Available Valsartan (VAL and Hydrochlorothiazide (HTZ are used in combination in treatment of Hypertension. Two simple, accurate, precise, economical and reproducible UV spectrophotometric methods have been developed for the estimation of Valsartan and Hydrochlorothiazide in Pharmaceutical formulation. Method I- Absorption ratio method (Q-analysis using two wavelengths, 265nm (isobestic point at which both the drugs exhibit absorbance 249nm (λmax of Valsartan and Method II- Area under Curve method. For the second method Area under the Curve in the range of 249 -259nm and 261-281nm was selected for the analysis of Valsartan and Hydrochlorothiazide respectively. Linearity for detector response was observed in the concentration range of 2-24g/ml & 2-14g/ml for Valsartan and Hydrochlorothiazide respectively. The results of analysis have been validated statistically and by recovery studies the value of standard deviation was satisfactory and recovery studies ranging from 99.54 - 99.97 % for Valsartan and 99.75 - 101.04 % for Hydrochlorothiazide were indicative of the accuracy and precision of the proposed method The proposed methods were successfully applied for the determination of Valsartan and Hydrochlorothiazide in commercial pharmaceutical preparation. All two methods were validated statistically as per ICH guidelines.

  18. A new derivative detected in accelerated ageing of artesunate-amodiaquine fixed dose combination tablets.

    Science.gov (United States)

    Charrier, Cedric; Bertho, Gildas; Petigny, Olivier; Moneton, Philippe; Azerad, Robert

    2013-01-01

    An unknown impurity detected in small amounts during the heat treatment of artesunate-amodiaquine bilayer tablets was purified by semipreparative HPLC and identified by MS and NMR as the tetrahydrofuranyl acetate-rearranged derivative of anhydrodihydroartemisinin. When anhydrodihydroartemisinin was treated with a Fe(II) salt in acetonitrile-water solution, the same product was generated, together with an isomeric 2-deoxy-4α-hydroxy-anhydrodihydroartemisinin derivative, as expected from the usual homolytic radical opening of the endoperoxide bond previously described for other artemisinin derivatives.

  19. Fixed-dose versus separate drug combinations for antihypertensive treatment: literature review

    Directory of Open Access Journals (Sweden)

    José Luis Calleja Rivero

    2016-09-01

    Full Text Available Resumen INTRODUCCIÓN La hipertensión arterial requiere de intervenciones efectivas para reducir la morbimortalidad cardiovascular. Las terapias farmacológicas han logrado alcanzar cifras óptimas de presión arterial en los afectados. En las guías clínicas recientes se sugiere la utilización de las combinaciones de medicamentos, esto ha llevado a elaborar una diversidad de combinaciones a dosis fija. OBJETIVO Buscar la mejor evidencia bibliográfica disponible sobre la efectividad de los medicamentos antihipertensivos en combinaciones a dosis fija, en comparación con combinaciones a dosis separadas para controlar la presión arterial, la adherencia al tratamiento y disminución de la morbimortalidad cardiovascular. MÉTODOS Se realizó una búsqueda sistemática de literatura de las mejores evidencias disponibles en las bases de datos: MEDLINE/PubMed, LILACS, Cochrane y publicaciones institucionales de la Organización Mundial de la Salud y Organización Panamericana de la Salud. RESULTADOS Del total de estudios encontrados, se seleccionaron dos metanálisis que compararon las dos combinaciones. En ambas se evaluó el cumplimiento de la medicación, no se evaluó el control de presión arterial o efectos en los eventos cardiovasculares. Ambos estudios son de muy baja calidad de evidencia por sus limitaciones en la búsqueda, calidad subóptima de los estudios incluidos y lo heterogéneo de las variables analizadas. En las políticas de medicamentos de la Organización Mundial de la Salud no se sugiere el uso de antihipertensivos con combinaciones a dosis fijas. En Chile no están incluidos en el formulario nacional de medicamentos. CONCLUSIÓN Se requieren estudios bien diseñados para demostrar la efectividad de los medicamentos antihipertensivos en combinación a dosis fijas en comparación con combinaciones a dosis separadas para control de la presión arterial, la adherencia al tratamiento y disminución de la morbimortalidad cardiovascular.

  20. Low-dose nitroglycerin improves microcirculation in hospitalized patients with acute heart failure

    NARCIS (Netherlands)

    C.A. den Uil; W.K. Lagrand; P.E. Spronk; M. van der Ent; L.S.D. Jewbali; J.J. Brugts; C. Ince; M.L. Simoons

    2009-01-01

    Impaired tissue perfusion is often observed in patients with acute heart failure. We tested whether low-dose nitroglycerin (NTG) improves microcirculatory perfusion in patients admitted for acute heart failure. In 20 acute heart failure patients, NTG was given as intravenous infusion at a fixed dose

  1. Duan's fixed point theorem: proof and generalization

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available Let X be an H-space of the homotopy type of a connected, finite CW-complex, f:X→X any map and p k :X→X the k th power map. Duan proved that p k f :X→X has a fixed point if k≥2 . We give a new, short and elementary proof of this. We then use rational homotopy to generalize to spaces X whose rational cohomology is the tensor product of an exterior algebra on odd dimensional generators with the tensor product of truncated polynomial algebras on even dimensional generators. The role of the power map is played by a θ -structure μ θ :X→X as defined by Hemmi-Morisugi-Ooshima. The conclusion is that μ θ f and f μ θ each has a fixed point.

  2. Fixing the shadows while moving the gnomon

    CERN Document Server

    Gangui, Alejandro

    2016-01-01

    It is a common practice to fix a vertical gnomon and study the moving shadow cast by it. This shows our local solar time and gives us a hint regarding the season in which we perform the observation. The moving shadow can also tell us our latitude with high precision. In this paper we propose to exchange the roles and while keeping the shadows fixed on the ground we will move the gnomon. This lets us understand in a simple way the relevance of the tropical lines of latitude and the behavior of shadows in different locations. We then put these ideas into practice using sticks and threads during a solstice on two sites located on opposite sides of the Tropic of Capricorn.

  3. Fixed Wordsize Implementation of Lifting Schemes

    Directory of Open Access Journals (Sweden)

    Tanja Karp

    2007-01-01

    Full Text Available We present a reversible nonlinear discrete wavelet transform with predefined fixed wordsize based on lifting schemes. Restricting the dynamic range of the wavelet domain coefficients due to a fixed wordsize may result in overflow. We show how this overflow has to be handled in order to maintain reversibility of the transform. We also perform an analysis on how large a wordsize of the wavelet coefficients is needed to perform optimal lossless and lossy compressions of images. The scheme is advantageous to well-known integer-to-integer transforms since the wordsize of adders and multipliers can be predefined and does not increase steadily. This also results in significant gains in hardware implementations.

  4. Selective fixed drug eruption to amoxycillin.

    Science.gov (United States)

    Arias, J; Férnandez-Rivas, M; Panadero, P

    1995-07-01

    A selective fixed drug eruption to amoxycillin but not other betalactam drugs is reported. Penicillins are the drugs most frequently implicated in immunological adverse reactions. The most important of these are allergic reactions where an IgE-mediated mechanism is well established. Other immunological mechanisms have been described in reactions, such as haemolytic anaemia, serum sickness, drug-induced nephritis, drug fever and contact dermatitis. Fixed drug eruption (FDE) is a type of drug-induced dermatosis, the immunopathogenesis of which remains unknown. FDE is an uncommon reaction to penicillin derivatives, and very few cases have been reported. We present a case of a selective FDE to amoxycillin (AX), with no reaction to other betalactam drugs. Although one similar case has been reported, the reactivity to other penicillin derivatives was not assessed.

  5. An Extension of Gregus Fixed Point Theorem

    Directory of Open Access Journals (Sweden)

    J. O. Olaleru

    2007-03-01

    Full Text Available Let C be a closed convex subset of a complete metrizable topological vector space (X,d and T:C→C a mapping that satisfies d(Tx,Ty≤ad(x,y+bd(x,Tx+cd(y,Ty+ed(y,Tx+fd(x,Ty for all x,y∈C, where 0fixed point. The above theorem, which is a generalization and an extension of the results of several authors, is proved in this paper. In addition, we use the Mann iteration to approximate the fixed point of T.

  6. Time Stamps for Fixed-Point Approximation

    DEFF Research Database (Denmark)

    Damian, Daniela

    2001-01-01

    Time stamps were introduced in Shivers's PhD thesis for approximating the result of a control-flow analysis. We show them to be suitable for computing program analyses where the space of results (e.g., control-flow graphs) is large. We formalize time-stamping as a top-down, fixed-point approximat......Time stamps were introduced in Shivers's PhD thesis for approximating the result of a control-flow analysis. We show them to be suitable for computing program analyses where the space of results (e.g., control-flow graphs) is large. We formalize time-stamping as a top-down, fixed......-point approximation algorithm which maintains a single copy of intermediate results. We then prove the correctness of this algorithm....

  7. Response of cellulose nitrate track detectors to electron doses

    CERN Document Server

    Segovia, N; Moreno, A; Vazquez-Polo, G; Santamaría, T; Aranda, P; Hernández, A

    1999-01-01

    In order to study alternative dose determination methods, the bulk etching velocity and the latent track annealing of LR 115 track detectors was studied during electron irradiation runs from a Pelletron accelerator. For this purpose alpha irradiated and blank detectors were exposed to increasing electron doses from 10.5 to 317.5 kGy. After the irradiation with electrons the detectors were etched under routine conditions, except for the etching time, that was varied for each electron dose in order to reach a fixed residual thickness. The variation of the bulk etching velocity as a function of each one of the electron doses supplied, was interpolated in order to obtain dosimetric response curves. The observed annealing effect on the latent tracks is discussed as a function of the total electron doses supplied and the temperature.

  8. Impulsive differential inclusions a fixed point approach

    CERN Document Server

    Ouahab, Abdelghani; Henderson, Johnny

    2013-01-01

    Impulsive differential equations have been developed in modeling impulsive problems in physics, population dynamics, ecology, biotechnology, industrial robotics, pharmacokinetics, optimal control, etc. The questions of existence and stability of solutions for different classes of initial values problems for impulsive differential equations and inclusions with fixed and variable moments are considered in detail. Attention is also given to boundary value problems and relative questions concerning differential equations. This monograph addresses a variety of side issues that arise from its simple

  9. The nonlinear fixed gravimetric boundary value problem

    Institute of Scientific and Technical Information of China (English)

    于锦海; 朱灼文

    1995-01-01

    The properly-posedness of the nonlinear fixed gravimetric boundary value problem is shown with the help of nonlinear functional analysis and a new iterative method to solve the problem is also given, where each step of the iterative program is reduced to solving one and the same kind of oblique derivative boundary value problem with the same type. Furthermore, the convergence of the iterative program is proved with Schauder estimate of elliptic differential equation.

  10. Fixed-Field Alternating-Gradient Accelerators

    CERN Document Server

    Sheehy, S L

    2016-01-01

    These notes provide an overview of Fixed-Field Alternating-Gradient (FFAG) accelerators for medical applications. We begin with a review of the basic principles of this type of accelerator, including the scaling and non-scaling types, highlighting beam dynamics issues that are of relevance to hadron ac- celerators. The potential of FFAG accelerators in the field of hadron therapy is discussed in detail, including an overview of existing medical FFAG designs. The options for FFAG treatment gantries are also considered.

  11. Morphing fixed wing MAV modeling using VAM

    OpenAIRE

    2012-01-01

    The design and implementation of a morphing Micro Air Vehicle (MAV) wing using a smart composite is attempted in this research work. Control surfaces actuated by traditional servos are difficult to instrument and fabricate on thin composite-wings of MAVs. Piezoelectric Fiber Reinforced Composites (PFRCs) are the chosen smart structural materials in the current work for incorporation onto fixed-wing MAVs to simultaneously perform the dual functions of structural load-bearing and actuatio...

  12. Optimal investment with fixed refinancing costs

    OpenAIRE

    Cummins, Jason G; Ingmar Nyman

    2001-01-01

    Case studies show that corporate managers seek financial independence to avoid interference by outside financiers. We incorporate this financial xenophobia as a fixed cost in a simple dynamic model of financing and investment. To avoid refinancing in the future, the firm alters its behavior depending on the extent of its financial xenophobia and the realization of a revenue shock. With a sufficiently adverse shock, the firm holds no liquidity. Otherwise, the firm precautionarily saves and hol...

  13. Low Actuation Voltage RF MEMS Switch Using Varying Section Composite Fixed-Fixed Beam

    Directory of Open Access Journals (Sweden)

    M. Manivannan

    2014-01-01

    Full Text Available The present authors have earlier reported the employment of varying section fixed-fixed beam for achieving lower pull-in voltage with marginal fall in restoring force. Reducing Young’s modulus also reduces the pull-in voltage but with lesser degree of reduction in restoring force. Composite beams are ideal alternatives to achieve decreased Young’s modulus. Hence new varying section composite fixed-fixed beam type RF MEMS switch has been proposed. The main advantage of this RF MEMS switch is that lower pull-in voltages can be achieved with marginal fall in stiction immunity. Spring constant of the proposed switch has been obtained using simulation studies and it has been shown that the spring constant and therefore the pull-in voltage (Vpi can be considerably reduced with the proposed switch. Simulation studies conducted on the proposed switch clearly demonstrate that the pull-in voltage can be reduced by 31.17% when compared to the varying section monolayer polysilicon fixed-fixed beam. Further this approach enables the designer to have more freedom to design lower pull-in voltage switches with improved stiction immunity.

  14. Fixed behaviours and migration in parasitic flatworms.

    Science.gov (United States)

    Sukhdeo, M V K; Sukhdeo, S C

    2002-03-01

    This paper considers how fixed behaviours may play a role in post-larval migrations of Entobdella soleae. A general argument is that a shift away from the paradigm of orientation is required to elucidate the mechanisms that parasites use to navigate on the surface of their hosts. Some migrations may rely on fixed behaviours (genetically programmed stereotyped behaviours) that often evolve under predictable environmental conditions with reliable signals. In turbulent and stochastic free-living environments, homeostatic hosts present very predictable topological substrates and physico-chemical characteristics to their parasites. Over the course of evolution on these predictable host substrates, adaptive behaviours in the parasites can become fixed. Examples of endoparasite migration behaviour, particularly that of the common liver fluke, Fasciola hepatica, will be used to develop an approach based on the perceptual worlds of migrating parasites. An important conclusion is that multi-disciplinary approaches, firmly rooted in an understanding of each parasite's natural history, are requisite to successful interpretation of migration behaviours on the host.

  15. Fixed point theory in distance spaces

    CERN Document Server

    Kirk, William

    2014-01-01

    This is a monograph on fixed point theory, covering the purely metric aspects of the theory–particularly results that do not depend on any algebraic structure of the underlying space. Traditionally, a large body of metric fixed point theory has been couched in a functional analytic framework. This aspect of the theory has been written about extensively. There are four classical fixed point theorems against which metric extensions are usually checked. These are, respectively, the Banach contraction mapping principal, Nadler’s well known set-valued extension of that theorem, the extension of Banach’s theorem to nonexpansive mappings, and Caristi’s theorem. These comparisons form a significant component of this book. This book is divided into three parts. Part I contains some aspects of the purely metric theory, especially Caristi’s theorem and a few of its many extensions. There is also a discussion of nonexpansive mappings, viewed in the context of logical foundations. Part I also contains certain re...

  16. Equipment selection heuristics for microwave fixed links

    Science.gov (United States)

    Flood, I. D.; Allen, S. M.

    2014-08-01

    Microwave fixed links use highly standardized radio equipment and, in the radio equipment standard referenced in this paper, there is a choice between exactly two radio systems when the assigner wishes to resolve a specific data rate exactly: one using a relatively lower-order modulation scheme and one a relatively higher-order scheme. Although the higher-order equipment requires less bandwidth for an isolated link, these systems radiate at higher powers and require larger protection ratios in the radio interference environment which lead to well-established trade-offs between modulation, bandwidth, equivalent isotropic radiated power, and frequency assignment criteria. Our earlier research showed that by extending the Frequency Assignment Problem to include equipment selection and using lower-order modulation equipment on selected links, we can actually reduce the overall span of frequencies required for a network frequency assignment. This work focused on the development of integer programming formulations and analyzed the exact solutions obtained. Exact solutions are impractical for real world problems; hence, here we focus on the development of heuristics for equipment selection. We can model the fixed link network as a complete graph where the vertices represent fixed link frequency assignment requests and the edges represent interference between pairs of vertices. Using a graph theoretic analysis of the interference problem, we propose heuristic techniques and discuss the relative success of our approach in this article.

  17. Breast dose reduction for chest CT by modifying the scanning parameters based on the pre-scan size-specific dose estimate (SSDE)

    Energy Technology Data Exchange (ETDEWEB)

    Kidoh, Masafumi; Utsunomiya, Daisuke; Oda, Seitaro; Nakaura, Takeshi; Yuki, Hideaki; Hirata, Kenichiro; Namimoto, Tomohiro; Sakabe, Daisuke; Hatemura, Masahiro; Yamashita, Yasuyuki [Kumamoto University, Department of Diagnostic Radiology, Faculty of Life Sciences, Honjo, Kumamoto (Japan); Funama, Yoshinori [Kumamoto University, Department of Medical Physics, Faculty of Life Sciences, Honjo, Kumamoto (Japan)

    2017-06-15

    To investigate the usefulness of modifying scanning parameters based on the size-specific dose estimate (SSDE) for a breast-dose reduction for chest CT. We scanned 26 women with a fixed volume CT dose index (CTDI{sub vol}) (15 mGy) and another 26 with a fixed SSDE (15 mGy) protocol (protocol 1 and 2, respectively). In protocol 2, tube current was calculated based on the patient habitus obtained on scout images. We compared the mean breast dose and the inter-patient breast dose variability and performed linear regression analysis of the breast dose and the body mass index (BMI) of the two protocols. The mean breast dose was about 35 % lower under protocol 2 than protocol 1 (10.9 mGy vs. 16.8 mGy, p < 0.01). The inter-patient breast dose variability was significantly lower under protocol 2 than 1 (1.2 mGy vs. 2.5 mGy, p < 0.01). We observed a moderate negative correlation between the breast dose and the BMI under protocol 1 (r = 0.43, p < 0.01); there was no significant correlation (r = 0.06, p = 0.35) under protocol 2. The SSDE-based protocol achieved a reduction in breast dose and in inter-patient breast dose variability. (orig.)

  18. Two prospective dosing methods for nortriptyline.

    Science.gov (United States)

    Perry, P J; Browne, J L; Alexander, B; Tsuang, M T; Sherman, A D; Dunner, F J

    1984-01-01

    This study compared two prospective pharmacokinetic dosing methods to predict steady-state concentrations of nortriptyline. One method required multiple determinations of the nortriptyline plasma concentration to estimate the drug's steady-state concentration. The second method required a single nortriptyline concentration drawn at a fixed time, preferably 36 hours, following a nortriptyline test dose. The 36-hour nortriptyline plasma concentrations (NTP 36h) were substituted into the straight-line equation of Cssav = 17.2 + 3.74 (NTP 36h), where Cssav is the average steady-state concentration for a 100 mg/day dose of nortriptyline. No differences were noted between the observed steady-state nortriptyline concentration of 121 +/- 19 ng/ml, the 36-hour single-point prediction mean concentration of 121 +/- 21 ng/ml, or the multiple-point prediction mean concentration of 122 +/- 19 ng/ml. Because of the similar findings between the two methods, the clinical advantages and disadvantages of each kinetic approach are discussed to put these prospective dosing protocols into their proper perspective.

  19. Fixed combinations in the pragmatic management of hypertension: focus on aliskiren and hydrochlorothiazide as a single pill

    Directory of Open Access Journals (Sweden)

    Michel Burnier

    2010-05-01

    Full Text Available Michel BurnierService of Nephrology and Hypertension, University Hospital, Lausanne, SwitzerlandAbstract: A majority of hypertensive patients need more than one antihypertensive drug to control their blood pressure. For this reason, most guidelines have introduced the possibility of prescribing fixed-dose combination therapies as first-line treatment in hypertension. Today, the concept of fixed-dose combinations has evolved and the term single pill combination might become more appropriate to reflect the large choice of drug combinations available on the market. Recently, a new single pill combination has been launched which combines the first direct renin inhibitor aliskiren and low doses of hydrochlorothiazide. This paper reviews the potential advantages of single pill combinations and presents the first results obtained with the aliskiren/HCTZ single pill combination in hypertension.Keywords: hypertension, drug adherence, combination therapies, diuretics, renin inhibition

  20. Nitrogen Fixing Legumes in the Plant Communities

    Directory of Open Access Journals (Sweden)

    M. A.A. Al-Fredan

    2011-01-01

    Full Text Available Problems statement: Numerous authors have used energetic to explain the ecological success of N-fixing plants. Legume biodiversity assessment, species dynamics, nitrogen fixation monitoring and environment impact assessment of these ecological events in Al-Hassa Oasis, Saudi Arabia are rare and need to be continuous and more frequent. Approach: Thus the objectives of this study were to analyze legume abundance within and outside Al-Hassa Oasis and relate it to the distribution of the different genera. Results: Thirty two legume plant species from 20 genera have been recorded within and outside the Oasis. The largest genera were Cassia (4 species, Indigofera (4 and Acacia (3. Annual herbs were the dominant growth form (34% of species recorded, followed by shrubs (28%, perennial herbs (19% and trees (19%. Eighteen alien plant species were recorded (maybe an underestimated number. The nitrogen fixation of the legume plant species in Al-Hassa Oasis was estimated/analyzing the fixing potentiality of these species and nonfixing reference species (Panicum turgidum using the 15N natural abundance method. Species with great nitrogen fixing capacity in Al-Hassa include: Medicago sativa, Vicia faba, Vicia sativa, Melitotus indicus, Dolicus lablab, Melitotus alba and Cliforia ternate. The mean biological fixation contribution of most of the recorded legume plants were high, varying from 3.9% (Indigofera argentea to 64.6% (Medicago sativa. Conclusion: Al-Hassa Oasis is richer than expected based on its location within the desert zone. This study confirms the importance of the Oasis for national flora conservation in the Kingdom. results showed a good potential for use of the 15N natural abundance methodology for evaluating the nitrogen fixation ability of the legume plants under field conditions as well as for the estimation of %Ndfa.

  1. Unconventional pontics in fixed partial dentures

    Directory of Open Access Journals (Sweden)

    Mansi Manish Oswal

    2016-01-01

    Full Text Available Clinical success of fixed prosthodontics is dependent in part upon the type of pontic design. The selection of pontic design plays an important role in the outcome of the treatment. At present, there are many different pontic designs and materials present in the market. For some patients, one pontic may have an advantage over another and the choice is a matter of preference with the operator. It is recognized that clinical circumstances will require infinite variations. Hence, the present study briefs about the unconventional pontic designs which can be used on regular basis for better clinical results.

  2. Lattice Chiral Fermions Through Gauge Fixing

    CERN Document Server

    Bock, W; Shamir, Y; Bock, Wolfgang; Golterman, Maarten; Shamir, Yigal

    1998-01-01

    We study a concrete lattice regularization of a U(1) chiral gauge theory. We use Wilson fermions, and include a Lorentz gauge-fixing term and a gauge-boson mass counterterm. For a reduced version of the model, in which the gauge fields are constrained to the trivial orbit, we show that there are no species doublers, and that the fermion spectrum contains only the desired states in the continuum limit, namely charged left-handed (LH) fermions and neutral right-handed (RH) fermions.

  3. Fixed-target physics at LHCb

    CERN Document Server

    Maurice, Emilie Amandine

    2017-01-01

    The LHCb experiment has the unique possibility, among the LHC experiments, to be operated in fixed target mode, using its internal gas target SMOG. The energy scale achievable at the LHC and the excellent detector capabilities for vertexing, tracking and particle identification allow a wealth of measurements of great interest for cosmic ray and heavy ions physics. We report the first measurements made in this configuration: the measurement of antiproton production in proton-helium collisions and the measurements of open and hidden charm production in proton-argon collisions at $\\sqrt{s_\\textrm{NN}} =$ 110 GeV.

  4. The universal cardinal ordering of fixed points

    Energy Technology Data Exchange (ETDEWEB)

    San Martin, Jesus [Departamento de Matematica Aplicada, E.U.I.T.I, Universidad Politecnica de Madrid, Ronda de Valencia 3, 28012 Madrid (Spain); Departamento de Fisica Matematica y Fluidos, U.N.E.D. Senda del Rey 9, 28040 Madrid (Spain); Moscoso, Ma Jose [Departamento de Matematica Aplicada, E.U.I.T.I, Universidad Politecnica de Madrid, Ronda de Valencia 3, 28012 Madrid (Spain); Gonzalez Gomez, A. [Departamento de Matematica Aplicada a los Recursos Naturales, E.T. Superior de Ingenieros de Montes, Universidad Politecnica de Madrid, 28040 Madrid (Spain)], E-mail: antonia.gonzalez@upm.es

    2009-11-30

    We present the theorem which determines, by a permutation, the cardinal ordering of fixed points for any orbit of a period doubling cascade. The inverse permutation generates the orbit and the symbolic sequence of the orbit is obtained as a corollary. Interestingly enough, it is important to point that this theorem needs no previous information about any other orbit; also the cardinal ordering is achieved automatically with no need to compare numerical values associated with every point of the orbit (as would be the case if kneading theory were used)

  5. Fixed points and controllability in delay systems

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available Schaefer's fixed point theorem is used to study the controllability in an infinite delay system x ′ ( t = G ( t , x t + ( B u ( t . A compact map or homotopy is constructed enabling us to show that if there is an a priori bound on all possible solutions of the companion control system x ′ ( t = λ [ G ( t , x t + ( B u ( t ] , 0 < λ < 1 , then there exists a solution for λ = 1 . The a priori bound is established by means of a Liapunov functional or applying an integral inequality. Applications to integral control systems are given to illustrate the approach.

  6. [Fixed appliances current state of the art].

    Science.gov (United States)

    Droschl, H; Eskici, A; Bantleon, H P; Muchitsch, A P

    1989-11-01

    Recent advances in fixed appliances are reviewed and discussed. These include cosmetically more appealing brackets (ceramic, lingual); new wires (nickel-titanium and titanium-molybdenum alloys); new biomechanical approaches (accurate computation of forces and torques according to Burstone resulting in the use of new mechanical concepts); experiences in the treatment of transplanted teeth made in the past 15 years; new approaches to the orthodontic finish (implementation of Andrews' "six keys to normal occlusion" with straight wires, accurate positioning of brackets, and gnathological positioners). Cases will be demonstrated.

  7. Chemical Separation of Fixed Tissue Using Thermolysin

    Directory of Open Access Journals (Sweden)

    Anahita Dua

    2013-01-01

    Full Text Available Thermolysin is a metallopeptidase used to cleave peptide bonds at specific junctions. It has previously been used to cleave specific amino acid sequences found at the junction of the sensory epithelium and underlying stroma of unfixed otolithic organs of the vestibular system. We have used thermolysin to separate sensory epithelium from the underlying stroma in fixed cristae ampullares of mouse, rat, gerbil, guinea pig, chinchilla, and tree squirrel, thus removing the saddle-shaped curvature of the sensory organ and creating a flattened sensory epithelium preparation. This permits visualization of the entire sensory organ in a single mount and facilitates proper morphometric analysis.

  8. Fixed kernel regression for voltammogram feature extraction

    Science.gov (United States)

    Acevedo Rodriguez, F. J.; López-Sastre, R. J.; Gil-Jiménez, P.; Ruiz-Reyes, N.; Maldonado Bascón, S.

    2009-12-01

    Cyclic voltammetry is an electroanalytical technique for obtaining information about substances under analysis without the need for complex flow systems. However, classifying the information in voltammograms obtained using this technique is difficult. In this paper, we propose the use of fixed kernel regression as a method for extracting features from these voltammograms, reducing the information to a few coefficients. The proposed approach has been applied to a wine classification problem with accuracy rates of over 98%. Although the method is described here for extracting voltammogram information, it can be used for other types of signals.

  9. Holographic non-Fermi-liquid fixed points.

    Science.gov (United States)

    Faulkner, Tom; Iqbal, Nabil; Liu, Hong; McGreevy, John; Vegh, David

    2011-04-28

    Techniques arising from string theory can be used to study assemblies of strongly interacting fermions. Via this 'holographic duality', various strongly coupled many-body systems are solved using an auxiliary theory of gravity. Simple holographic realizations of finite density exhibit single-particle spectral functions with sharp Fermi surfaces, of a form distinct from those of the Landau theory. The self-energy is given by a correlation function in an infrared (IR) fixed-point theory that is represented by a two-dimensional anti de Sitter space (AdS(2)) region in the dual gravitational description. Here, we describe in detail the gravity calculation of this IR correlation function.

  10. CERN's Fixed Target Primary Ion Programme

    CERN Document Server

    Manglunki, Django; Axensalva, Jerome; Bellodi, Giulia; Blas, Alfred; Bodendorfer, Michael; Bohl, Thomas; Cettour-Cave, Stephane; Cornelis, Karel; Damerau, Heiko; Efthymiopoulos, Ilias; Fabich, Adrian; Ferreira Somoza, Jose; Findlay, Alan; Freyermuth, Pierre; Gilardoni, Simone; Hancock, Steven; Holzer, Eva Barbara; Jensen, Steen; Kain, Verena; Küchler, Detlef; Lombardi, Alessandra; Michet, Alice; O'Neil, Michael; Pasinelli, Sergio; Scrivens, Richard; Steerenberg, Rende; Tranquille, Gerard

    2016-01-01

    The renewed availability of heavy ions at CERN for the needs of the LHC programme has triggered the interest of the fixed-target community. The project, which involves sending several species of primary ions at various energies to the North Area of the Super Proton Synchrotron, has now entered its operational phase. The first argon run, with momenta ranging from 13 AGeV/c to 150 AGeV/c, took place from February 2015 to April 2015. This paper presents the status of the project, the performance achieved thus far and an outlook on future plans.

  11. Controllable dose; Dosis controlable

    Energy Technology Data Exchange (ETDEWEB)

    Alvarez R, J.T.; Anaya M, R.A. [ININ, A.P. 18-1027, 11801 Mexico D.F. (Mexico)]. E-mail: jtar@nuclear.inin.mx

    2004-07-01

    With the purpose of eliminating the controversy about the lineal hypothesis without threshold which found the systems of dose limitation of the recommendations of ICRP 26 and 60, at the end of last decade R. Clarke president of the ICRP proposed the concept of Controllable Dose: as the dose or dose sum that an individual receives from a particular source which can be reasonably controllable by means of any means; said concept proposes a change in the philosophy of the radiological protection of its concern by social approaches to an individual focus. In this work a panorama of the foundations is presented, convenient and inconveniences that this proposal has loosened in the international community of the radiological protection, with the purpose of to familiarize to our Mexican community in radiological protection with these new concepts. (Author)

  12. MEIR-KEELER TYPE CONTRACTIONS FOR TRIPLED FIXED POINTS

    Institute of Scientific and Technical Information of China (English)

    Hassen Aydi; Erdal Karapinar; Calogero Vetro

    2012-01-01

    In 2011,Berinde and Borcut [6] introduced the notion of tripled fixed point in partially ordered metric spaces.In our paper,we give some new tripled fixed point theorems by using a generalization of Meir-Keeler contraction.

  13. A Dual of the Compression-Expansion Fixed Point Theorems

    Directory of Open Access Journals (Sweden)

    Henderson Johnny

    2007-01-01

    Full Text Available This paper presents a dual of the fixed point theorems of compression and expansion of functional type as well as the original Leggett-Williams fixed point theorem. The multi-valued situation is also discussed.

  14. The Mapping Synthesis of Ternary Functions under Fixed Polarities

    Institute of Scientific and Technical Information of China (English)

    陈偕雄; 吴浩敏

    1993-01-01

    This paper proposes a mapping method simplifying the Reed-Muller expansion(“RM expansion”)of a ternary function under fixed polarities and the transformation of the RM expansion coefficients with different fixed polarities.

  15. Fixed Points for Pseudocontractive Mappings on Unbounded Domains

    Directory of Open Access Journals (Sweden)

    García-Falset Jesús

    2010-01-01

    Full Text Available We give some fixed point results for pseudocontractive mappings on nonbounded domains which allow us to obtain generalizations of recent fixed point theorems of Penot, Isac, and Németh. An application to integral equations is given.

  16. Weight-based combination therapy with peginterferon alpha-2b and ribavirin for Naïve, relapser and non-responder patients with chronic hepatitis C

    Directory of Open Access Journals (Sweden)

    Fernando Lopes Gonçales Jr.

    2006-10-01

    Full Text Available Combination therapy with pegylated interferon and ribavirin is considered the new standard therapy for naïve patients with chronic hepatitis C. We evaluated the efficacy and safety of treatment with weight-based peginterferon alpha-2b (1.5 mg/kg per week plus ribavirin (800-1,200 mg/day for 48 weeks in naïve, relapser and non-responder (to previous treatment with interferon plus ribavirin patients with chronic hepatitis C. Sixty-seven naïve, 26 relapser and 40 non-responder patients were enrolled. The overall sustained virological response (SVR for the intention-to-treat population was 54% for naïve, 62% for relapser and 38% for non-responder patients. In the naïve subgroup, SVR was significantly higher in patients with the non-1 genotype (67% compared to those with genotype 1 (45%. In relapsers and non-responders, SVR was, respectively, 69% and 24% in patients with genotype 1 and 43% and 73% in those with genotype non-1. There were no significant differences in SVR rates among the three body weight ranges ( 85 kg in any of the subgroups. Early virological response (EVR was reached by 78%, 81% and 58% of naïve, relapser and non-responder patients, respectively, and among those with EVR, 63%, 67% and 61%, respectively, subsequently achieved SVR. All of the non-responder patients who did not have EVR reached SVR. Treatment was discontinued in 13% of the patients, due to loss to follow-up, hematological abnormalities or depression.

  17. 基于熵权的乡村旅游人口特征分析%Entropy-weight-based Analysis on Characteristics of Agritourist Population

    Institute of Scientific and Technical Information of China (English)

    游武; 许丽忠

    2012-01-01

    用一种基于熵权的旅游人口特性的分析方法,通过采集目前国内的部分乡村旅游研究案例,对乡村旅游人口的人口学特征进行分析,认为目前乡村旅游人口中,性别属性与年龄属性空间差异相对不大,但游客的经济收入水平空间差异大,同时游客的文化教育构成也有一定的变化。在进行乡村旅游客源市场调查时,应将游客的经济结构调查放在首位,同时还应对客源市场的文化教育层次进行细致的调查,针对客源市场的特点,有的放矢地设计旅游产品。%Agritourism is a "win-win" tourist pattern, while there is little literature on the traveling population. An entropy-weight-based analysis method is put forward in this thesis to discuss the traveling population character. By study- ing several native agritourism cases, we found that it was little spatial divergence in population gender attribute or age attribute while it was large in economic and education attributes. So when we design the tourism market, we should focus on the tourism's economical and educational structure in order to shoot the arrow at the target.

  18. Fixed Costs and Asset Market Participation Fixed Costs and Asset Market Participation

    Directory of Open Access Journals (Sweden)

    Harold H. Zhang

    2000-03-01

    Full Text Available This paper investigates the effects of fixed costs on investor's decision of asset market participation. The model features a continuum of agents with heterogeneous initial wealth and attitude toward risk. We show that under certain conditions there exists a unique competitive equilibrium in which investors optimally choose to stay in autarky, participate just in the riskless asset market or in both the riskless and the risky asset markets. The model is calibrated based on earnings profile from the U.S. We find that using fixed costs that are comparable to the current commission charged by brokers the model can generate participation patterns similar to observed ones. Further, we find participation rates to be very sensitive to the costs differentials associated with entering the risky asset market while relatively less sensitive to the overall levels of fixed costs. Finally, we find that costs make it even harder for dynamic models to replicate the risk free rate and in that sense deepen that puzzle. This paper investigates the effects of fixed costs on investor's decision of asset market participation. The model features a continuum of agents with heterogeneous initial wealth and attitude toward risk. We show that under certain conditions there exists a unique competitive equilibrium in which investors optimally choose to stay in autarky, participate just in the riskless asset market or in both the riskless and the risky asset markets. The model is calibrated based on earnings profile from the U.S. We find that using fixed costs that are comparable to the current commission charged by brokers the model can generate participation patterns similar to observed ones. Further, we find participation rates to be very sensitive to the costs differentials associated with entering the risky asset market while relatively less sensitive to the overall levels of fixed costs. Finally, we find that costs make it even harder for dynamic models to replicate

  19. Long-term evaluation of cantilevered versus fixed-fixed resin-bonded fixed partial dentures for missing maxillary incisors.

    Science.gov (United States)

    Botelho, Michael G; Chan, Alex W K; Leung, Nic C H; Lam, Walter Y H

    2016-02-01

    To evaluate the long-term longevity and patient-reported outcomes of two-unit cantilevered (CL2) and three-unit fixed-fixed (FF3) resin-bonded fixed partial dentures (RBFPDs) for the replacement of a maxillary permanent incisor. Twenty-eight subjects were randomly assigned to receive either a CL2 or FF3 RBFPD placed by one operator. Prosthesis longevity was determined by clinical examination and history. Success was defined as absence of complications requiring intervention and survival as retention of the original prosthesis in mouth. Subjects' satisfaction was assessed using visual analogue scale (VAS) and oral health-related quality of life (OHRQoL) using Oral Health Impact Profile (OHIP-49). Outcomes were analysed with t-test/Mann-Whitney U test, chi-square and log-rank test at significance level α=0.05. Twenty-two subjects were reviewed. Thirteen of fifteen CL2 and ten of fourteen FF3 RBFPDs were examined (79.3 percent response rate) with a mean service life of 216.5±20.8months. All CL2 RBFPDs survived with no complications while only 10 percent of FF3 experienced no complications and only 50 percent of them survived (both P=0.000). CL2 had a significantly better success and survival rate than FF3 (P=0.000 and P=0.009, respectively). There was no significant difference in subjects' satisfaction and OHRQoL apart from CL2 group subjects had a higher satisfaction in cleaning of the prosthesis (84.1±13.6) than FF3 group (72.6±11.7) (P=0.05). Two-unit cantilevered RBFPDs were observed to have a significantly better success and survival than the FF3 design for the replacement of a maxillary incisor. Good patient-reported outcomes have been found for RBFPDs in single-tooth replacement in aesthetic zone. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. 47 CFR 22.1031 - Temporary fixed stations.

    Science.gov (United States)

    2010-10-01

    ... MOBILE SERVICES Offshore Radiotelephone Service § 22.1031 Temporary fixed stations. The FCC may, upon proper application therefor, authorize the construction and operation of temporary fixed stations in the... the United States and Mexico must not be carried using a temporary fixed station without...

  1. Fixed Points of -Endomorphisms of a Free Metabelian Lie Algebra

    Indian Academy of Sciences (India)

    Naime Ekici; Demet Parlak Sönmez

    2011-11-01

    Let be a free metabelian Lie algebra of finite rank at least 2. We show the existence of non-trivial fixed points of an -endomorphism of and give an algorithm detecting them. In particular, we prove that the fixed point subalgebra Fix of an -endomorphism of is not finitely generated.

  2. GPU implementation of a Landau gauge fixing algorithm

    CERN Document Server

    Cardoso, Nuno; Oliveira, Orlando; Bicudo, Pedro

    2012-01-01

    We discuss how the steepest descent method with Fourier acceleration for Laudau gauge fixing in lattice SU(3) simulations can be implemented using CUDA. The scaling of the gauge fixing code was investigated using a Tesla C2070 Fermi architecture, and compared with a parallel CPU gauge fixing code.

  3. 33 CFR 118.65 - Lights on fixed bridges.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Lights on fixed bridges. 118.65 Section 118.65 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES BRIDGE LIGHTING AND OTHER SIGNALS § 118.65 Lights on fixed bridges. (a) Each fixed bridge span over a...

  4. Classification system for conventional crown and fixed partial denture failures.

    Science.gov (United States)

    Manappallil, John Joy

    2008-04-01

    The dental literature is replete with reports on the many aspects of failure encountered with traditional fixed prosthodontic treatment, including longitudinal survival studies of crowns and fixed partial dentures and reasons for failures. However, criteria for grading or classifying the type and severity of these failures are inadequate. A classification system for conventional fixed prosthodontic failures based on severity is presented.

  5. 46 CFR 28.320 - Fixed gas fire extinguishing systems.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Fixed gas fire extinguishing systems. 28.320 Section 28..., 1991, and That Operate With More Than 16 Individuals on Board § 28.320 Fixed gas fire extinguishing...) or more in length must be fitted with a fixed gas fire extinguishing system in the following...

  6. On Fixed Points of Linguistic Dynamic Systems

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Linguistic dynamic systems (LDS) are dynamic systems whose state variables are generalized from numbers to words. Generally speaking, LDS can model all evolving processes in word domains by using linguistic evolving laws which are naturally the linguistic extension of evolving laws in numbers. There are two kinds of LDS; namely, type-I and type-II LDS. If the word domain is modeled by fuzzy sets, then the evolving laws of a type-I LDS are constructed by applying the fuzzy extension principle to those of its conventional counterpart. On the other hand, the evolving laws of a type-II LDS are modeled by fuzzy if/then rules. Note that the state spaces of both type-I and type-II LDSs are word continuum. However, in practice, the representation of the state space of a type-II LDS consists of finite number while its computation actually involves a word continuum. In this paper, the existence of fixed points of type-II LDS is studied based on point-to-fuzzy-set mappings. The properties of the fixed point of type-II LDS are also studied. In addition, linguistic controllers are designed to control type-II LDS to goal states specified in words.

  7. Duan's fixed point theorem: Proof and generalization

    Directory of Open Access Journals (Sweden)

    Martin Arkowitz

    2006-02-01

    Full Text Available Let X be an H-space of the homotopy type of a connected, finite CW-complex, f:X→X any map and pk:X→X the kth power map. Duan proved that pkf:X→X has a fixed point if k≥2. We give a new, short and elementary proof of this. We then use rational homotopy to generalize to spaces X whose rational cohomology is the tensor product of an exterior algebra on odd dimensional generators with the tensor product of truncated polynomial algebras on even dimensional generators. The role of the power map is played by a θ-structure μθ:X→X as defined by Hemmi-Morisugi-Ooshima. The conclusion is that μθf and fμθ each has a fixed point.

  8. Random and fixed effects in plant genetics.

    Science.gov (United States)

    Cockerham, C C

    1980-05-01

    A general model for any type of genetic entry is developed which takes into account both the factorial model of gene effects and the ancestral sources, whether inbred lines or outbred varieties, of the genes.Utilizing the model, various genetic designs of fixed entries are explored for the estimation of genetic effects and the testing of genetic hypotheses. These designs consisted of generation means - parents, crosses, various types of backcrosses, and so on - stemming from one or more pairs of parents, and of hybrid combinations from factorial mating designs. Limitations, from the standpoint of genetic effects that can be estimated and genetic hypotheses that can be tested, are developed in considerable detail.When entries from the factorial mating designs are considered to be random, attention is focused on the estimation of genetic variances, rather than effects, and on the concomitant changes in the tests of genetic hypotheses. While there is considerable improvement over fixed entries in the number of types of genetic variances that can be estimated, and of genetic hypotheses that can be tested, they are still very limited in contrast to what would be most desirable.

  9. Fixed Drug Eruption due to Achiote Dye

    Directory of Open Access Journals (Sweden)

    Ian Tattersall

    2016-01-01

    Full Text Available Fixed drug eruption (FDE is a localized type IV sensitivity reaction to a systemically introduced allergen. It usually occurs as a result of new medication, making identification and avoidance of the trigger medication straightforward; however, in a rare subset of cases no pharmacological source is identified. In such cases, the causative agent is often a food or food additive. In this report we describe a case of a FDE in a 12-year-old girl recently immigrated to the United States from Ecuador who had no medication exposure over the course of her illness. Through an exhaustive patient history and literature review, we were able to hypothesize that her presentation was caused by a dietary change of the natural achiote dye used in the preparation of yellow rice to a locally available commercial dye mix containing tartrazine, or Yellow 5, which has previously been implicated in both systemic hypersensitivity reactions and specifically in FDE. This report adds to the small body of available literature on non-pharmacological fixed hypersensitivity eruptions and illustrates an effective approach to the management of such a presentation when history is not immediately revealing.

  10. Fixed Drug Eruption due to Achiote Dye

    Science.gov (United States)

    Tattersall, Ian; Reddy, Bobby Y.

    2016-01-01

    Fixed drug eruption (FDE) is a localized type IV sensitivity reaction to a systemically introduced allergen. It usually occurs as a result of new medication, making identification and avoidance of the trigger medication straightforward; however, in a rare subset of cases no pharmacological source is identified. In such cases, the causative agent is often a food or food additive. In this report we describe a case of a FDE in a 12-year-old girl recently immigrated to the United States from Ecuador who had no medication exposure over the course of her illness. Through an exhaustive patient history and literature review, we were able to hypothesize that her presentation was caused by a dietary change of the natural achiote dye used in the preparation of yellow rice to a locally available commercial dye mix containing tartrazine, or Yellow 5, which has previously been implicated in both systemic hypersensitivity reactions and specifically in FDE. This report adds to the small body of available literature on non-pharmacological fixed hypersensitivity eruptions and illustrates an effective approach to the management of such a presentation when history is not immediately revealing. PMID:26933409

  11. Fixed Drug Eruption due to Achiote Dye.

    Science.gov (United States)

    Tattersall, Ian; Reddy, Bobby Y

    2016-01-01

    Fixed drug eruption (FDE) is a localized type IV sensitivity reaction to a systemically introduced allergen. It usually occurs as a result of new medication, making identification and avoidance of the trigger medication straightforward; however, in a rare subset of cases no pharmacological source is identified. In such cases, the causative agent is often a food or food additive. In this report we describe a case of a FDE in a 12-year-old girl recently immigrated to the United States from Ecuador who had no medication exposure over the course of her illness. Through an exhaustive patient history and literature review, we were able to hypothesize that her presentation was caused by a dietary change of the natural achiote dye used in the preparation of yellow rice to a locally available commercial dye mix containing tartrazine, or Yellow 5, which has previously been implicated in both systemic hypersensitivity reactions and specifically in FDE. This report adds to the small body of available literature on non-pharmacological fixed hypersensitivity eruptions and illustrates an effective approach to the management of such a presentation when history is not immediately revealing.

  12. Therapeutic effect of Linum usitatissimum (flaxseed/linseed) fixed oil on acute and chronic arthritic models in albino rats.

    Science.gov (United States)

    Kaithwas, Gaurav; Majumdar, Dipak K

    2010-06-01

    The present study was undertaken to assess the activity/anti-inflammatory potential of Linum usitatissimum fixed oil against castor oil-induced diarrhoea, turpentine oil-induced joint oedema, formaldehyde and Complete Freund's Adjuvant (CFA)-induced arthritis in Wistar albino rats. The oil intraperitoneally, significantly inhibited the castor oil-induced diarrhoea and turpentine oil-induced exudative joint oedema in a dose-dependent manner. Significant inhibitory effect of L. usitatissimum fixed oil was observed in formaldehyde-induced proliferative global oedematous arthritis when given intraperitoneally, with significant checking of the serum glutamic oxaloacetic acid transaminase and serum glutamic pyruvic acid transaminase. Further, L. usitatissimum fixed oil showed a significant dose-dependent protective effect against CFA-induced arthritis as well. Secondary lesions produced by CFA due to a delayed hypersensitivity reaction were also reduced in a significant manner. Anti-inflammatory activity of L. usitatissimum fixed oil can be attributed to the presence of alpha linolenic acid (57.38%, an omega-3 fatty acid, 18:3, n-3) having dual inhibitory effect on arachidonate metabolism resulting in suppressed production of proinflammatory n-6 eicosanoids (PGE(2), LTB(4)) and diminished vascular permeability. These observations suggest possible therapeutic potential of L. usitatissimum fixed oil in inflammatory disorders like rheumatoid arthritis.

  13. Dosimetrically determined doses of radioiodine for the treatment of metastatic thyroid carcinoma.

    Science.gov (United States)

    Van Nostrand, Douglas; Atkins, Frank; Yeganeh, Fred; Acio, Elmo; Bursaw, Randy; Wartofsky, Leonard

    2002-02-01

    In the absence of definitive studies relating radioiodine dose to outcomes, selection of a dose of radioiodine to treat metastatic thyroid carcinoma is problematic, and several approaches have been used. These include empiric fixed doses and doses used on dosimetric approaches specific for each patient. This paper is a review of the rationale and technique for dosimetrically-determined doses of radioiodine for the treatment of metastatic thyroid carcinoma. This review (1) discusses the alternatives for selection of a dose, (2) discusses the two major approaches for determining radioiodine doses dosimetrically, (3) briefly reviews several modifications of these approaches, (4) reviews the literature regarding the results, (5) discusses the side effects of these different approaches, and (6) concludes with recommendations for patient management and future research. This review does not address use of dosimetrically-determined doses of radioiodine for the initial ablation of thyroid tissue postoperatively.

  14. Utirik Atoll Dose Assessment

    Energy Technology Data Exchange (ETDEWEB)

    Robison, W.L.; Conrado, C.L.; Bogen, K.T

    1999-10-06

    On March 1, 1954, radioactive fallout from the nuclear test at Bikini Atoll code-named BRAVO was deposited on Utirik Atoll which lies about 187 km (300 miles) east of Bikini Atoll. The residents of Utirik were evacuated three days after the fallout started and returned to their atoll in May 1954. In this report we provide a final dose assessment for current conditions at the atoll based on extensive data generated from samples collected in 1993 and 1994. The estimated population average maximum annual effective dose using a diet including imported foods is 0.037 mSv y{sup -1} (3.7 mrem y{sup -1}). The 95% confidence limits are within a factor of three of their population average value. The population average integrated effective dose over 30-, 50-, and 70-y is 0.84 mSv (84, mrem), 1.2 mSv (120 mrem), and 1.4 mSv (140 mrem), respectively. The 95% confidence limits on the population-average value post 1998, i.e., the 30-, 50-, and 70-y integral doses, are within a factor of two of the mean value and are independent of time, t, for t > 5 y. Cesium-137 ({sup 137}Cs) is the radionuclide that contributes most of this dose, mostly through the terrestrial food chain and secondarily from external gamma exposure. The dose from weapons-related radionuclides is very low and of no consequence to the health of the population. The annual background doses in the U. S. and Europe are 3.0 mSv (300 mrem), and 2.4 mSv (240 mrem), respectively. The annual background dose in the Marshall Islands is estimated to be 1.4 mSv (140 mrem). The total estimated combined Marshall Islands background dose plus the weapons-related dose is about 1.5 mSv y{sup -1} (150 mrem y{sup -1}) which can be directly compared to the annual background effective dose of 3.0 mSv y{sup -1} (300 mrem y{sup -1}) for the U. S. and 2.4 mSv y{sup -1} (240 mrem y{sup -1}) for Europe. Moreover, the doses listed in this report are based only on the radiological decay of {sup 137}Cs (30.1 y half-life) and other

  15. Competition and facilitation between unicellular nitrogen-fixing cyanobacteria and non-nitrogen-fixing phytoplankton species

    NARCIS (Netherlands)

    Agawin, N.S.; Rabouille, S.; Veldhuis, M.; Servatius, L.; Hol, S.; van Overzee, H.M.J.; Huisman, J.

    2007-01-01

    Abstract: Recent discoveries show that small unicellular nitrogen-fixing cyanobacteria are more widespread than previously thought and can make major contributions to the nitrogen budget of the oceans. We combined theory and experiments to investigate competition for nitrogen and light between these

  16. Comparison of the efficacy and safety of intensive-dose and standard-dose statin treatment for stroke prevention

    Science.gov (United States)

    Wang, Juan; Chen, Dan; Li, Da-Bing; Yu, Xin; Shi, Guo-Bing

    2016-01-01

    Abstract Background: Previous study indicated that high-dose statin treatment might increase the risk of hemorrhagic stroke and adverse reactions. We aim to compare the efficacy and safety of intensive-dose and standard-dose statin treatment for preventing stroke in high-risk patients. Methods: A thorough search was performed of multiple databases for publications from 1990 to June 2015. We selected the randomized clinical trials comparing standard-dose statin with placebo and intensive-dose statin with standard-dose statin or placebo for the prevention of stroke events in patients. Duplicate independent data extraction and bias assessments were performed. Data were pooled using a fixed-effects model or a random-effects model if significant heterogeneity was present. Results: For the all stroke incidences, intensive-dose statin treatment compared with placebo treatment and standard-dose statin treatment compared with placebo treatment showed a significant 21% reduction in relative risk (RR) (RR 0.79, 95% confidence interval (CI) [0.71, 0.87], P statin treatment compared with standard dose or placebo was effective reducing fatal stroke (RR 0.61, 95% CI [0.39, 0.96], P = 0.03) and the RR was 1.01 (95% CI [0.85, 1.20], P = 0.90) in standard-dose statin treatment compared with placebo. Conclusion: The results of this meta-analysis suggest that intensive-dose statin treatment might be more favorable for reducing the incidences of all strokes than standard-dose statin treatment, especially for patients older than 65 years in reducing the incidences of all stroke incidences. PMID:27684837

  17. Safety and tolerability of fixed antihypertensive combinations in blood pressure control: focus on olmesartan medoxomil and amlodipine combination

    Directory of Open Access Journals (Sweden)

    Ijlal Uddin

    2010-11-01

    Full Text Available Ijlal Uddin, Shakil AslamDivision of Nephrology and Hypertension, Georgetown University Hospital, Washington, District of Columbia, USAAbstract: Hypertension is a major health problem worldwide and remains underdiagnosed and undertreated. Although public awareness and control of hypertension have improved over the last decade, only one-third of hypertensive patients achieve the rather conservative blood pressure (BP goal of <140/90 mmHg. Most hypertensive patients require more than one drug for optimum BP control. Expert panels recommend use of combination therapy with two or more medications for Stage 2 and higher hypertension and in high-risk patients. However, the use of multiple drugs reduces patient compliance. Fixed-dose combination therapy helps improve patient compliance and thus achieve the target BP. Dose titration of the individual constituent drugs is recommended before switching to an equivalent fixed-dose combination. Randomized, controlled trials have shown that the fixed-dose combination of amlodipine–olmesartan medoxomil is more effective in lowering BP than monotherapy with either of these agents, with a similar side effect profile.Keywords: hypertension, target blood pressure, compliance, amlodipine, olmesartan

  18. Assessment of internal doses

    CERN Document Server

    Rahola, T; Falk, R; Isaksson, M; Skuterud, L

    2002-01-01

    There is a definite need for training in dose calculation. Our first course was successful and was followed by a second, both courses were fully booked. An example of new tools for software products for bioassay analysis and internal dose assessment is the Integrated Modules for Bioassay Analysis (IMBA) were demonstrated at the second course. This suite of quality assured code modules have been adopted in the UK as the standard for regulatory assessment purposes. The intercomparison measurements are an important part of the Quality Assurance work. In what is known as the sup O utside workers ' directive it is stated that the internal dose measurements shall be included in the European Unions supervision system for radiation protection. The emergency preparedness regarding internal contamination was much improved by the training with and calibration of handheld instruments from participants' laboratories. More improvement will be gained with the handbook giving practical instructions on what to do in case of e...

  19. Biofilm formation enables free-living nitrogen-fixing rhizobacteria to fix nitrogen under aerobic conditions.

    Science.gov (United States)

    Wang, Di; Xu, Anming; Elmerich, Claudine; Ma, Luyan Z

    2017-07-01

    The multicellular communities of microorganisms known as biofilms are of high significance in agricultural setting, yet it is largely unknown about the biofilm formed by nitrogen-fixing bacteria. Here we report the biofilm formation by Pseudomonas stutzeri A1501, a free-living rhizospheric bacterium, capable of fixing nitrogen under microaerobic and nitrogen-limiting conditions. P. stutzeri A1501 tended to form biofilm in minimal media, especially under nitrogen depletion condition. Under such growth condition, the biofilms formed at the air-liquid interface (termed as pellicles) and the colony biofilms on agar plates exhibited nitrogenase activity in air. The two kinds of biofilms both contained large ovoid shape 'cells' that were multiple living bacteria embedded in a sac of extracellular polymeric substances (EPSs). We proposed to name such large 'cells' as A1501 cyst. Our results suggest that the EPS, especially exopolysaccharides enabled the encased bacteria to fix nitrogen while grown under aerobic condition. The formation of A1501 cysts was reversible in response to the changes of carbon or nitrogen source status. A1501 cyst formation depended on nitrogen-limiting signaling and the presence of sufficient carbon sources, yet was independent of an active nitrogenase. The pellicles formed by Azospirillum brasilense, another free-living nitrogen-fixing rhizobacterium, which also exhibited nitrogenase activity and contained the large EPS-encapsuled A1501 cyst-like 'cells'. Our data imply that free-living nitrogen-fixing bacteria could convert the easy-used carbon sources to exopolysaccharides in order to enable nitrogen fixation in a natural aerobic environment.

  20. Fixed drug eruption due to levocetirizine

    Directory of Open Access Journals (Sweden)

    Ratinder Jhaj

    2016-01-01

    Full Text Available A fixed drug eruption (FDE is a cutaneous adverse drug reaction due to Type IV or delayed cell-mediated hypersensitivity. Antihistamines, which antagonize the action of histamine during an allergic reaction by blocking the H 1 histamine receptors, are used routinely for the treatment of various allergic disorders such as urticaria, eczemas, and also in itchy lesions of skin like scabies.Levocetirizine, an active (R-enantiomer of cetirizine, is a newer or second generation antihistamine, with more specific actions and fewer side effects, including cutaneous reactions. FDE due to levocetirizine as well as with cetirizine are rare. We report a case of levocetirizine induced FDE in a 49-year-old male patient with scabies. The patient had a history of cetirizine induced FDE in the past.

  1. Recursive double-size fixed precision arithmetic

    CERN Document Server

    Chabot, Christophe; Fousse, Laurent; Giorgi, Pascal

    2011-01-01

    This work is a part of the SHIVA (Secured Hardware Immune Versatile Architecture) project whose purpose is to provide a programmable and reconfigurable hardware module with high level of security. We propose a recursive double-size fixed precision arithmetic called RecInt. Our work can be split in two parts. First we developped a C++ software library with performances comparable to GMP ones. Secondly our simple representation of the integers allows an implementation on FPGA. Our idea is to consider sizes that are a power of 2 and to apply doubling techniques to implement them efficiently: we design a recursive data structure where integers of size 2^k, for k>k0 can be stored as two integers of size 2^{k-1}. Obviously for k<=k0 we use machine arithmetic instead (k0 depending on the architecture).

  2. [Update on protein analysis of fixed tissues].

    Science.gov (United States)

    Becker, K-F; Berg, D; Malinowsky, K; Wolff, C; Ergin, B; Meding, S; Walch, A; Höfler, H

    2010-10-01

    Tissue samples have been routinely used for decades to distinguish healthy from diseased tissue in histopathological characterization. While nucleic acid-based methodologies have been successfully in use for many years, protein-based techniques, in contrast, are at a very early stage (with the exception of immunohistochemistry). One reason for this delay may be that the scientific community has long thought that formalin-fixed and paraffin embedded (FFPE) tissues are unfit for protein analysis. However, recent reports demonstrate that many protein methods that are routinely used for frozen tissues can also be applied for FFPE tissues, including Western blot, protein microarray, matrix-assisted laser desorption/ionization (MALDI) imaging and 2D gel electrophoresis. The present article provides an overview of recent developments in this field, focussing particular attention on quantitative analysis and high throughput technologies that have the potential to be integrated into the routine workflow of clinical pathology laboratories.

  3. Fixed bed gasification of solid biomass fuels

    Energy Technology Data Exchange (ETDEWEB)

    Haavisto, I. [Condens Oy, Haemeenlinna (Finland)

    1996-12-31

    Fixed bed biomass gasifiers are feasible in the effect range of 100 kW -10 MW. Co-current gasification is available only up to 1 MW for technical reasons. Counter-current gasifiers have been used in Finland and Sweden for 10 years in gasification heating plants, which are a combination of a gasifier and an oil boiler. The plants have proved to have a wide control range, flexible and uncomplicated unmanned operation and an excellent reliability. Counter-current gasifiers can be applied for new heating plants or for converting existing oil and natural gas boilers into using solid fuels. There is a new process development underway, aiming at motor use of the producer gas. The development work involves a new, more flexible cocurrent gasifier and a cleaning step for the counter-current producer gas. (orig.)

  4. Equilibria, Fixed Points, and Complexity Classes

    CERN Document Server

    Yannakakis, Mihalis

    2008-01-01

    Many models from a variety of areas involve the computation of an equilibrium or fixed point of some kind. Examples include Nash equilibria in games; market equilibria; computing optimal strategies and the values of competitive games (stochastic and other games); stable configurations of neural networks; analysing basic stochastic models for evolution like branching processes and for language like stochastic context-free grammars; and models that incorporate the basic primitives of probability and recursion like recursive Markov chains. It is not known whether these problems can be solved in polynomial time. There are certain common computational principles underlying different types of equilibria, which are captured by the complexity classes PLS, PPAD, and FIXP. Representative complete problems for these classes are respectively, pure Nash equilibria in games where they are guaranteed to exist, (mixed) Nash equilibria in 2-player normal form games, and (mixed) Nash equilibria in normal form games with 3 (or ...

  5. Fixed point theorems for generalized Lipschitzian semigroups

    Directory of Open Access Journals (Sweden)

    Jong Soo Jung

    2001-01-01

    semigroup of K into itself, that is, for s∈G, ‖Tsx−Tsy‖≤as‖x−y‖+bs(‖x−Tsx‖+‖y−Tsy‖+cs(‖x−Tsy‖+‖y−Tsx‖, for x,y∈K where as,bs,cs>0 such that there exists a t1∈G such that bs+cs<1 for all s≽t1. It is proved that if there exists a closed subset C of K such that ⋂sco¯{Ttx:t≽s}⊂C for all x∈K, then with [(α+βp(αp⋅2p−1−1/(cp−2p−1βp⋅Np]1/p<1 has a common fixed point, where α=lim sups(as+bs+cs/(1-bs-cs and β=lim sups(2bs+2cs/(1-bs-cs.

  6. Lifting fixed points of completely positive semigroups

    CERN Document Server

    Prunaru, Bebe

    2011-01-01

    Let $\\{\\phi_s\\}_{s\\in S}$ be a commutative semigroup of completely positive and contractive linear maps acting on a von Neumann algebra $N$. Assume there exists a semigroup $\\{\\alpha_s\\}_{s\\in S}$ of *-endomorphisms of some larger von Neumann algebra $M\\supset N$ and a projection $p\\in M$ with $N=pMp$ such that $\\alpha_s(1-p)\\le 1-p$ for every $s\\in S$ and $\\phi_s(y)=p\\alpha_s(y)p$ for all $y\\in N$. If $\\inf_{s\\in S}\\alpha_s(1-p)=0$ then we show that the map $E:M\\to N$ defined by $E(x)=pxp$ for $x\\in M$ induces a complete isometry between the fixed point spaces of $\\{\\alpha_s\\}_{s\\in S}$ and $\\{\\phi_s\\}_{s\\in S}$.

  7. Galvanic gold plating for fixed dental prosthesis.

    Science.gov (United States)

    Ozcelik, Tuncer Burak; Yilmaz, Burak

    2013-07-01

    Metal ceramic partial fixed dental prostheses have been commonly used for the replacement of missing teeth for many years. Because of an increase in the price of gold, base metal alloys have been the choice of alloy for the fabrication of metal ceramic restorations in many dental clinics. Some major disadvantages of base metals are their corrosion and the dark coloration they may cause at the crown margins. This article describes a galvanic gold-plating technique, which is used to minimize corrosion and improve the esthetics of metal ceramic restorations fabricated with Cr-Co base metal alloys. This technique involves the deposition of a 6 μm to 8 μm 24 K gold layer directly onto the Cr-Co cast prosthesis framework. The technique improves metal surface properties, making them more biocompatible and usable, however, requires additional equipment and experienced laboratory technicians. Clinical studies should be performed to corroborate the long term success of this technique.

  8. On Krasnoselskii's Cone Fixed Point Theorem

    Directory of Open Access Journals (Sweden)

    Man Kam Kwong

    2008-04-01

    Full Text Available In recent years, the Krasnoselskii fixed point theorem for cone maps and its many generalizations have been successfully applied to establish the existence of multiple solutions in the study of boundary value problems of various types. In the first part of this paper, we revisit the Krasnoselskii theorem, in a more topological perspective, and show that it can be deduced in an elementary way from the classical Brouwer-Schauder theorem. This viewpoint also leads to a topology-theoretic generalization of the theorem. In the second part of the paper, we extend the cone theorem in a different direction using the notion of retraction and show that a stronger form of the often cited Leggett-Williams theorem is a special case of this extension.

  9. Fixed target experiments at the Fermilab Tevatron

    CERN Document Server

    Gutierrez, Gaston

    2014-01-01

    This paper presents a review of the study of Exclusive Central Production at a Center of Mass energy of $\\sqrt{s}=40$ GeV at the Fermilab Fixed Target program. In all reactions reviewed in this paper, protons with an energy of 800 GeV were extracted from the Tevatron accelerator at Fermilab and directed to a Liquid Hydrogen target. The states reviewed include $\\pi^+\\pi^-$, $K^0_s K^0_s$, $ K^0_sK^\\pm\\pi^\\mp$, $\\phi\\phi$ and $D^{*\\pm}$. Partial Wave Analysis results will be presented on the light states but only the cross section will be reviewed in the diffractive production of $D^{*\\pm}$

  10. Fixed Points for Stochastic Open Chemical Systems

    CERN Document Server

    Malyshev, V A

    2011-01-01

    In the first part of this paper we give a short review of the hierarchy of stochastic models, related to physical chemistry. In the basement of this hierarchy there are two models --- stochastic chemical kinetics and the Kac model for Boltzman equation. Classical chemical kinetics and chemical thermodynamics are obtained as some scaling limits in the models, introduced below. In the second part of this paper we specify some simple class of open chemical reaction systems, where one can still prove the existence of attracting fixed points. For example, Michaelis\\tire Menten kinetics belongs to this class. At the end we present a simplest possible model of the biological network. It is a network of networks (of closed chemical reaction systems, called compartments), so that the only source of nonreversibility is the matter exchange (transport) with the environment and between the compartments. Keywords: chemical kinetics, chemical thermodynamics, Kac model, mathematical biology

  11. Pseudoephedrine may cause "pigmenting" fixed drug eruption.

    Science.gov (United States)

    Ozkaya, Esen; Elinç-Aslan, Meryem Sevinç

    2011-05-01

    Fixed drug eruption (FDE) is a distinctive drug eruption characterized by recurrent well-defined lesions in the same location each time the responsible drug is taken. Two different clinical forms have been described: the common classic pigmenting form and the rare nonpigmenting form. Nonpigmenting FDE is mainly characterized by symmetrical large erythematous plaques and the dermal histopathologic reaction pattern. Pseudoephedrine is known as the major inducer of nonpigmenting FDE. Pigmenting FDE from pseudoephedrine has not been reported previously. Here, the first case of pseudoephedrine-induced pigmenting FDE is reported, showing the characteristic features of classic pigmenting FDE such as asymmetry, normal-sized lesions, and the epidermodermal histopathologic reaction pattern. Moreover, a positive occlusive patch-test reaction to pseudoephedrine could be demonstrated on postlesional FDE skin for the first time.

  12. Meprobamate-induced fixed drug eruption.

    Science.gov (United States)

    Zaïem, Ahmed; Kaabi, Widd; Badri, Talel; Lakhoua, Ghozlane; Sahnoun, Rym; Kastalli, Sarrah; Daghfous, Riadh; Lakhal, Mohamed; El Aidli, Sihem

    2014-01-01

    Meprobamate is usually a safe drug prescribed for anxiety disorders. Fixed drug eruption (FDE) is an exceptional cutaneous adverse effect of this drug. We report a case of FDE induced by meprobamate with positive patch test. A 22-year-old woman was prescribed for depression meprobamate, aceprometazine, valpromide and lorazepam. On the second day of treatment, the patient presented red erythematous and pruriginous plaques in the limbs and the face. After stopping the previous treatment, the patient's lesions resolved completely within 3 weeks with residual pigmentation. One month later, patch tests were performed and were positive to meprobamate. Exceptional cases of FDE were reported in literature with meprobamate. None has reported the use of patch test to confirm the diagnosis.

  13. Steiner trees for fixed orientation metrics

    DEFF Research Database (Denmark)

    Brazil, Marcus; Zachariasen, Martin

    2009-01-01

    We consider the problem of constructing Steiner minimum trees for a metric defined by a polygonal unit circle (corresponding to s = 2 weighted legal orientations in the plane). A linear-time algorithm to enumerate all angle configurations for degree three Steiner points is given. We provide...... a simple proof that the angle configuration for a Steiner point extends to all Steiner points in a full Steiner minimum tree, such that at most six orientations suffice for edges in a full Steiner minimum tree. We show that the concept of canonical forms originally introduced for the uniform orientation...... metric generalises to the fixed orientation metric. Finally, we give an O(s n) time algorithm to compute a Steiner minimum tree for a given full Steiner topology with n terminal leaves....

  14. Dose to patient in tomosynthesis; Dosis a paciente en tomosintesis

    Energy Technology Data Exchange (ETDEWEB)

    Minambres Moro, A.; Fernandez Leton, P.; Garcia Rui-Zorrilla, J.; Perez Moreno, J. M.; Zucca Aparicio, D.

    2013-07-01

    They are beginning to implement digital mammography with the possibility of acquiring in tomosynthesis, whose biggest advantage is to distinguish structures without overlapping through of pseudotridimensionals images. With these modified mammograms can acquire a planar mammography, with fixed x-ray tube, or a tomosynthesis with tube by turning. For acquire tomosynthesis is necessary a detector of high efficiency together with tungsten white tubes. The objective of this study is to know the dose received by the patient with this new imaging. (Author)

  15. Dose Reduction Techniques

    Energy Technology Data Exchange (ETDEWEB)

    WAGGONER, L.O.

    2000-05-16

    As radiation safety specialists, one of the things we are required to do is evaluate tools, equipment, materials and work practices and decide whether the use of these products or work practices will reduce radiation dose or risk to the environment. There is a tendency for many workers that work with radioactive material to accomplish radiological work the same way they have always done it rather than look for new technology or change their work practices. New technology is being developed all the time that can make radiological work easier and result in less radiation dose to the worker or reduce the possibility that contamination will be spread to the environment. As we discuss the various tools and techniques that reduce radiation dose, keep in mind that the radiological controls should be reasonable. We can not always get the dose to zero, so we must try to accomplish the work efficiently and cost-effectively. There are times we may have to accept there is only so much you can do. The goal is to do the smart things that protect the worker but do not hinder him while the task is being accomplished. In addition, we should not demand that large amounts of money be spent for equipment that has marginal value in order to save a few millirem. We have broken the handout into sections that should simplify the presentation. Time, distance, shielding, and source reduction are methods used to reduce dose and are covered in Part I on work execution. We then look at operational considerations, radiological design parameters, and discuss the characteristics of personnel who deal with ALARA. This handout should give you an overview of what it takes to have an effective dose reduction program.

  16. Do foliar endophytic bacteria fix nitrogen?

    Science.gov (United States)

    Kueppers, L. M.; Moyes, A. B.; Frank, C.; Pett-Ridge, J.; Carper, D.; Vandehey, N.; O'Neil, J.; Dekas, A.

    2015-12-01

    Endophytic microorganisms - bacteria and fungi that live inside healthy plant tissue - are a relatively unexplored source of functional diversity in natural ecosystems. Prior to modern sequencing technology, detecting uncultured endophytic bacteria and assessing their putative functions was challenging. However, recent work has revealed a remarkable diversity of as yet non-culturable endophytic taxa and is beginning to identify functional roles within plant microbiomes. We recently examined bacterial communities in the foliage of a long-lived, high-elevation conifer species, limber pine (Pinus flexilis), and discovered a community strongly dominated by acetic acid bacteria (Acetobacteraceae), with several taxa closely related to known nitrogen fixers. Given limber pine's status as a pioneer species that is able to grow in low fertility soils, we hypothesized that this bacterial community has a potential functional role in fixing atmospheric nitrogen, providing a source of this limiting nutrient to the host tree. We used the radioisotope 13N2 to confirm that N2 rapidly diffuses into pine needles, where it could potentially be fixed. With an acetylene reduction assay we confirmed nitrogenase enzyme activity inside excised twigs 4 times over a growing season, and estimate potential rates of N2 fixation at 0.1 nmol N2 g needle-1 hr-1. Scaled to the stand level, this N input could be on the order of ~20 mg N m-2 d-1 over a growing season. While these rates are low, the long lifespan of individual trees (~1000 years) makes them biologically meaningful. Still, measured rates of acetylene reduction and bulk 15N2 incorporation are quite variable in space and time. Much work remains to better characterize the plant-microbial interactions in this system, including the rates of nitrogen fixation and their variability over the growing season, across edaphic conditions, among host species, and through plant development; and to determine which community members are responsible

  17. High-dose vs low-dose proton pump inhibitors for upper gastrointestinal bleeding: a meta-analysis.

    Science.gov (United States)

    Wu, Liu-Cheng; Cao, Yun-Fei; Huang, Jia-Hao; Liao, Cun; Gao, Feng

    2010-05-28

    To evaluate the efficacy of high-dose proton pump inhibitors (PPIs) vs low-dose PPIs for patients with upper gastrointestinal bleeding. PubMed, Embase, the Cochrane Library, and Web of Science were searched to identify relevant randomized controlled trials (RCTs). Eligible trials were RCTs that compared high-dose PPI with low-dose PPI following endoscopic hemostasis. The primary endpoint was rebleeding; secondary endpoints were patient numbers that needed surgery, and mortality. The meta-analysis was performed with a fixed effects model or random effects model. Nine eligible RCTs including 1342 patients were retrieved. The results showed that high-dose intravenous PPI was not superior to low-dose intravenous PPI in reducing rebleeding [odds ratio (OR) = 1.091, 95% confidential interval (CI): 0.777-1.532], need for surgery (OR = 1.522, 95% CI: 0.643-3.605) and mortality (OR = 1.022, 95% CI: 0.476-2.196). Subgroup analysis according to different region revealed no difference in rebleeding rate between Asian patients (OR = 0.831, 95% CI, 0.467-1.480) and European patients (OR = 1.263, 95% CI: 0.827-1.929). Low-dose intravenous PPI can achieve the same efficacy as high-dose PPI following endoscopic hemostasis.

  18. Iterative reconstruction technique with reduced volume CT dose index: diagnostic accuracy in pediatric acute appendicitis

    Energy Technology Data Exchange (ETDEWEB)

    Didier, Ryne A. [Oregon Health and Science University, Department of Diagnostic Radiology, DC7R, Portland, OR (United States); Vajtai, Petra L. [Oregon Health and Science University, Department of Pediatrics, Portland, OR (United States); Oregon Health and Science University, Department of Diagnostic Radiology, DC7R, Portland, OR (United States); Hopkins, Katharine L. [Oregon Health and Science University, Department of Diagnostic Radiology, DC7R, Portland, OR (United States); Oregon Health and Science University, Department of Pediatrics, Portland, OR (United States)

    2014-07-05

    Iterative reconstruction technique has been proposed as a means of reducing patient radiation dose in pediatric CT. Yet, the effect of such reductions on diagnostic accuracy has not been thoroughly evaluated. This study compares accuracy of diagnosing pediatric acute appendicitis using contrast-enhanced abdominopelvic CT scans performed with traditional pediatric weight-based protocols and filtered back projection reconstruction vs. a filtered back projection/iterative reconstruction technique blend with reduced volume CT dose index (CTDI{sub vol}). Results of pediatric contrast-enhanced abdominopelvic CT scans done for pain and/or suspected appendicitis were reviewed in two groups: A, 192 scans performed with the hospital's established weight-based CT protocols and filtered back projection reconstruction; B, 194 scans performed with iterative reconstruction technique and reduced CTDI{sub vol}. Reduced CTDI{sub vol} was achieved primarily by reductions in effective tube current-time product (mAs{sub eff}) and tube peak kilovoltage (kVp). CT interpretation was correlated with clinical follow-up and/or surgical pathology. CTDI{sub vol}, size-specific dose estimates (SSDE) and performance characteristics of the two CT techniques were then compared. Between groups A and B, mean CTDI{sub vol} was reduced by 45%, and mean SSDE was reduced by 46%. Sensitivity, specificity and diagnostic accuracy were 96%, 97% and 96% in group A vs. 100%, 99% and 99% in group B. Accuracy in diagnosing pediatric acute appendicitis was maintained in contrast-enhanced abdominopelvic CT scans that incorporated iterative reconstruction technique, despite reductions in mean CTDI{sub vol} and SSDE by nearly half as compared to the hospital's traditional weight-based protocols. (orig.)

  19. Dose Reduction Techniques

    CERN Document Server

    Waggoner, L O

    2000-01-01

    As radiation safety specialists, one of the things we are required to do is evaluate tools, equipment, materials and work practices and decide whether the use of these products or work practices will reduce radiation dose or risk to the environment. There is a tendency for many workers that work with radioactive material to accomplish radiological work the same way they have always done it rather than look for new technology or change their work practices. New technology is being developed all the time that can make radiological work easier and result in less radiation dose to the worker or reduce the possibility that contamination will be spread to the environment. As we discuss the various tools and techniques that reduce radiation dose, keep in mind that the radiological controls should be reasonable. We can not always get the dose to zero, so we must try to accomplish the work efficiently and cost-effectively. There are times we may have to accept there is only so much you can do. The goal is to do the sm...

  20. T dose Vaccine Policy

    African Journals Online (AJOL)

    National Programme of Immunization (NPI), measles remains a disturbing cause ... or as a supplement is expected to offer a second opportunity to children who ... available in 1963, the world welcomed it with joy .... one dose of vaccine were not always protected from .... begins a long story Starting now is still early enough.