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Sample records for therapy fixed combinations

  1. Considerations in glaucoma therapy: fixed combinations versus their component medications

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    Eve J Higginbotham

    2009-12-01

    Full Text Available Eve J HigginbothamMorehouse School of Medicine, Atlanta, GA, USAAbstract: Fixed combinations of medications that lower intraocular pressure (IOP are increasingly used in the treatment of glaucoma and ocular hypertension and offer several potential advantages over combined use of the separate component medications including enhanced convenience, improved adherence, reduced exposure to preservatives, and possible cost savings. This review aims to examine the current role of IOP-lowering fixed combinations in disease management. The results of studies that compared the efficacy and safety of IOP-lowering fixed combinations with their component medications are summarized, including those fixed combinations that consist of a prostaglandin analog and timolol. The fixed combinations currently available for use in the United States are fixed-combination dorzolamide/timolol (FCDT and fixed-combination brimonidine/timolol (FCBT. Both of these fixed combinations reduce IOP more effectively than their component medications used separately as monotherapy. FCBT therapy also demonstrates a more favorable safety profile and reduced ocular allergy compared to monotherapy with brimonidine, a component medication. Few studies have directly compared the efficacy and safety of FCDT and FCBT, but available evidence suggests that FCBT is at least as effective as FCDT in lowering IOP and is more comfortable and better tolerated. Additional studies are needed to further evaluate the comparative efficacy and tolerability of FCDT and FCBT in the management of glaucoma and ocular hypertension.Keywords: glaucoma, intraocular pressure, fixed combination, adherence, brimonidine

  2. 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

  3. 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

  4. 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

  5. Comparison of therapy persistence for fixed versus free combination antihypertensives: a retrospective cohort study

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    Grimmsmann, Thomas; Himmel, Wolfgang

    2016-01-01

    Objectives The aim of the study was to compare therapy persistence among patients who started with one of three drug regimens: a monotherapy, or combination therapy either as a fixed combination (ie, ‘single pill’) or as a free combination (ie, two separate antihypertensive agents). Design In a secondary data analysis, we used descriptive statistics and multivariate logistic regression to measure the effect of the three therapy regimens on therapy persistence over 4 years. Setting Prescription data from a large German statutory health insurance provider. Participants All patients who started with a new antihypertensive therapy in 2007 or 2008 (n=8032) were included and followed for 4 years. Primary outcome measure Therapy persistence, defined as receiving a refill prescription no later than within 180 days. Results The persistence rates after 4 years were nearly identical among patients who started with a monotherapy (40.3%) or a fixed combination of two drugs (39.8%). However, significantly more patients who started with free-drug combinations remained therapy persistent (56.4%), resulting in an OR of 2.00 (95% CI 1.6 to 2.5; p<0.0001) for free combinations versus fixed combinations. This trend was observed in all age groups and for men and women. At the end of the study period, the number of different antihypertensive agents was still similar between patients who started with a fixed combination (2.41) and patients who started with a free combination (2.28). Conclusions While single-pill combinations make it easier to take different drugs at once, the risk is high that these several substances are stopped at once. Therapy persistence was significantly better for patients who started with a free-drug combination without taking much fewer different antihypertensive drugs as those with a fixed combination. PMID:27881519

  6. [One year adherence of ramipril versus ramipril/amlodipine fixed dose combination therapy in hypertension].

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    Simonyi, Gábor; Ferenci, Tamás

    2017-10-01

    In the treatment of hypertension avoiding adverse cardiovascular complications to achieve target blood pressure is essential. The appropriate drug selection, and if necessary to change to combination therapy, patients adherence is important which may help fixed dose combination. The aim of the authors was to investigate the one year adherence of the ramipril and ramipril/amlodipine fixed dose combination in hypertensive patients. Prescriptions database of the National Health Insurance Fund in Hungary on pharmacy-claims was analysed between October 1, 2012 and September 30, 2013. The authors identified patients who filled prescriptions for ramipril monotherapy and fixed dose combinations of ramipril/amlodipine prescribed for the first time in hypertensive patients who have not received similar drugs in the previous year. To model the adherence, the apparatus of survival analysis was used, where "survival" was the time to abandon the medication. As it was available to month precision, discrete time survival analysis was applied: a generalized linear model was estimated with complementary log-log link function with the kind of drug being the only explanatory variable. 92,546 patients met the inclusion criteria. During the trial period, ramipril therapy or ramipril/amlodipine fixed dose combination was started in 82,251 and 10,295 patients, respectively. One year persistence rate in patients with ramipril was 30% and 54% in patients with ramipril/amlodipine fixed dose combination therapy. Considering only the 360-day study period, the mean duration of persistence was 189.9 days in patients on ramipril and 270.6 days on ramipril/amlodipine fixed dose combination therapy. The hazard of discontinuation was more than twofold higher during treatment with ramipril compared with the use of the ramipril/amlodipine fixed dose combination therapy (HR = 2.11 [95% CI: 2.05-2.17], p<0,001). There is a significant difference between the one year persistence of ramipril and ramipril

  7. The impact of timolol maleate on the ocular tolerability of fixed-combination glaucoma therapies

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    Radcliffe NM

    2014-12-01

    Full Text Available Nathan M Radcliffe Ophthalmology, New York University, New York, NY, USA Abstract: Glaucomatous optic atrophy is the second most common cause of blindness worldwide, and lowering intraocular pressure (IOP is the only proven method to slow or stop the progression of the disease. Approximately 40% of patients with elevated IOP will require more than one medication to obtain a modest 20% reduction in IOP, and as a result, some patients may require two medications, provided in either two separate bottles or in one bottle with the use of fixed-combination therapies. Each therapy has its own unique safety and efficacy profile. Topical beta-blockers have a particularly favorable ocular-tolerability profile, and several studies of fixed-combination medications containing the beta-blocker timolol maleate have shown a lower prevalence of some ocular adverse events for the fixed-combination therapy compared to the non-beta-blocker individual component. In this review, we examined clinical data pertaining to the ocular surface tolerability of fixed-combination medications containing timolol maleate in comparison to the individual components. In particular, preference was given to prospective, randomized, multicenter trials of 3 months in duration or longer that compared a fixed-combination therapy to monotherapy with the individual components. A review of the literature revealed that some fixed-combination therapies can provide a reduced risk of common side effects compared to their individual components, with conjunctival hyperemia and ocular allergy being less frequent in some timolol-containing fixed-combination therapies. This effect appears to be most significant for latanoprost 0.005%, bimatoprost 0.03%, and brimonidine 0.2%. Keywords: bimatoprost, brimonidine, hyperemia, latanoprost, ocular allergy

  8. Fixed-dose combination therapy for the prevention of atherosclerotic cardiovascular diseases.

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    Bahiru, Ehete; de Cates, Angharad N; Farr, Matthew Rb; Jarvis, Morag C; Palla, Mohan; Rees, Karen; Ebrahim, Shah; Huffman, Mark D

    2017-03-06

    Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death and disability worldwide, yet ASCVD risk factor control and secondary prevention rates remain low. A fixed-dose combination of blood pressure- and cholesterol-lowering and antiplatelet treatments into a single pill, or polypill, has been proposed as one strategy to reduce the global burden of ASCVD. To determine the effect of fixed-dose combination therapy on all-cause mortality, fatal and non-fatal ASCVD events, and adverse events. We also sought to determine the effect of fixed-dose combination therapy on blood pressure, lipids, adherence, discontinuation rates, health-related quality of life, and costs. We updated our previous searches in September 2016 of CENTRAL, MEDLINE, Embase, ISI Web of Science, and DARE, HTA, and HEED. We also searched two clinical trials registers in September 2016. We used no language restrictions. We included randomised controlled trials of a fixed-dose combination therapy including at least one blood pressure-lowering and one lipid-lowering component versus usual care, placebo, or an active drug comparator for any treatment duration in adults 18 years old or older, with no restrictions on presence or absence of pre-existing ASCVD. Three review authors independently selected studies for inclusion and extracted the data for this update. We evaluated risk of bias using the Cochrane 'Risk of bias' assessment tool. We calculated risk ratios (RR) for dichotomous data and mean differences (MD) for continuous data with 95% confidence intervals (CI) using fixed-effect models when heterogeneity was low (I2 50%) and random-effects models when heterogeneity was high (I2 ≥ 50%). We used the GRADE approach to evaluate the quality of evidence. In the initial review, we identified nine randomised controlled trials with a total of 7047 participants and four additional trials (n = 2012 participants; mean age range 62 to 63 years; 30% to 37% women) were included in this

  9. Antioxidant activity of dorzolamide/timolol fixed combination in neuroprotective therapy in glaucoma

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    N. I. Kurysheva

    2012-01-01

    Full Text Available Purpose: to study the antioxidant activity of carbonic anhydrase inhibitors and timolol fixed combinations and to compare it with other fixed combinations.Methods: Antioxidant activity (AOA of dorzolamide/timolol (Cosopt, dorzolamide/timolol (Dorzopt Plus, latanoprost/timolol, brimonidine/timolol, travoprost/timolol and bimatoprost/timolol fixed combinations was measured in vitro using the model of oxida- tive hemolysis.Results: Dorzolamide/timolol (Cosopt AOA was higher than that of other fixed combinations and increased with the quantity of the drugs added to the model system: 40%, 52% and 75% in 30 μl, 60 μl and 90 μl respectively.Conclusion: these findings suggest that dorzolamide/timolol fixed combination has potential advantages over the other fixed combinations due to its high antioxidant activity and might be used as the neuroptotective agent for glaucoma treatment.

  10. Antioxidant activity of dorzolamide/timolol fixed combination in neuroprotective therapy in glaucoma

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    N. I. Kurysheva

    2014-07-01

    Full Text Available Purpose: to study the antioxidant activity of carbonic anhydrase inhibitors and timolol fixed combinations and to compare it with other fixed combinations.Methods: Antioxidant activity (AOA of dorzolamide/timolol (Cosopt, dorzolamide/timolol (Dorzopt Plus, latanoprost/timolol, brimonidine/timolol, travoprost/timolol and bimatoprost/timolol fixed combinations was measured in vitro using the model of oxida- tive hemolysis.Results: Dorzolamide/timolol (Cosopt AOA was higher than that of other fixed combinations and increased with the quantity of the drugs added to the model system: 40%, 52% and 75% in 30 μl, 60 μl and 90 μl respectively.Conclusion: these findings suggest that dorzolamide/timolol fixed combination has potential advantages over the other fixed combinations due to its high antioxidant activity and might be used as the neuroptotective agent for glaucoma treatment.

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

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

    2017-08-04

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

  12. Triple therapy in COPD: new evidence with the extrafine fixed combination of beclomethasone dipropionate, formoterol fumarate, and glycopyrronium bromide

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    Singh D

    2017-10-01

    Full Text Available Dave Singh,1 Massimo Corradi,2 Monica Spinola,3 Alberto Papi,4 Omar S Usmani,5 Mario Scuri,3 Stefano Petruzzelli,3 Jørgen Vestbo1 1Division of Infection, Immunity and Respiratory Medicine, University of Manchester, Manchester, UK; 2Department of Medicine and Surgery, University of Parma, Parma, Italy; 3Chiesi Farmaceutici SpA, Parma, Italy; 4Department of Medical Sciences, Research Centre on Asthma and COPD, University of Ferrara, Ferrara, Italy; 5National Heart and Lung Institute, Imperial College London, London, UK Abstract: The goals of COPD therapy are to prevent and control symptoms, reduce the frequency and severity of exacerbations, and improve exercise tolerance. The triple combination therapy of inhaled corticosteroids (ICSs, long-acting beta2 agonists (LABAs, and long-acting muscarinic antagonists (LAMAs has become an option for maintenance treatment of COPD and as a “step-up” therapy from single or double combination treatments. There is evidence that triple combination ICS/LABA/LAMA with different inhalers improves lung function, symptoms, and health status and reduces exacerbations. A new triple fixed-dose combination of extrafine beclomethasone dipropionate (100 µg/puff/formoterol fumarate (6 µg/puff/glycopyrronium bromide (12.5 µg/puff has been developed as a hydrofluoroalkane pressurized metered dose inhaler. Two large pivotal studies showed that this extrafine fixed ICS/LABA/LAMA triple combination is superior to fixed ICS/LABA combined therapy and also superior to the LAMA tiotropium in terms of lung function and exacerbation prevention in COPD patients at risk of exacerbation. This review considers the new information provided by these clinical trials of extrafine triple therapy and the implications for the clinical management of COPD patients. Keywords: COPD, inhaled triple therapy, beclomethasone dipropionate, formoterol fumarate and glycopyrronium bromide

  13. Adherence to oral antidiabetic agents with pioglitazone and metformin: comparison of fixed-dose combination therapy with monotherapy and loose-dose combination therapy.

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    Barner, Jamie C

    2011-09-01

    Several studies have examined adherence when switching from loose-dose combination therapy (LDCT) to fixed-dose combination therapy (FDCT) among oral antidiabetic agents. However, little is known regarding combination therapies, including pioglitazone and metformin. The objectives of this study were (1) to describe adherence to monotherapy (MT), LDCT, and FDCT of oral diabetic agents containing pioglitazone and metformin; (2) to determine whether there are differences in the medication adherence of patients switching from MT or LDCT to the corresponding FDCT, while controlling for covariates; and (3) to determine whether there are differences in medication costs between LDCT and the analogous FDCT. This retrospective database study included continuously enrolled Texas Medicaid recipients (18-65 years) who were prescribed FDCT with pioglitazone and metformin in the postindex period and prescribed the analogous LDCT or MT in the preindex period. Prescription claims were extracted from August 1, 2004, to August 31, 2007. Medication possession ratio (MPR) was used to measure medication adherence, and medication costs were assessed using reimbursement amount to dispensing pharmacies. Descriptive statistics, paired t tests, χ(2) tests, and logistic regression analyses were employed to address the study objectives. Patients (n = 270) were on average (mean [SD]) 50.7 (9.7) years of age, and the majority were female (73.3%). Overall adherence to FDCT was 80.5 (19.7). Regarding patients who switched from LDCT (n = 60) to FDCT, adherence increased significantly (P = 0.0081) by 8.9% (76.0 [16.8] to 82.8 [18.2]), whereas those who switched from MT (n = 210) to FDCT had a 9% significant (P pioglitazone and metformin resulted in a 9% decrease in medication cost and a 9% increase in adherence. Caution should be used when generalizing the study results to different FDCT combinations and other payers. Copyright © 2011 Elsevier HS Journals, Inc. All rights reserved.

  14. A cost-effectiveness analysis of fixed-combination therapies in patients with open-angle glaucoma: a European perspective

    DEFF Research Database (Denmark)

    Hommer, A.; Wickstrom, J.; Friis, M.M.

    2008-01-01

    inclusive of value-added tax, and visit costs were priced using official physician fees. Cost-effectiveness analyses were carried out in five European countries: Spain, Italy, United Kingdom, Norway and Sweden. The time horizon for the analyses was 3 months. RESULTS: The analysis showed that fixed......OBJECTIVE: To compare the efficacy and cost implications of the use of the intraocular pressure-lowering prostaglandin analogues bimatoprost, travoprost, and latanoprost as fixed-combination therapies with timolol, a beta-adrenergic receptor antagonist. METHODS: A decision analytic cost......, time horizon, patient population and type of end point presented. The measure of effectiveness was the percentage reduction of the intraocular pressure level from baseline. The cost evaluated was the cost of medication and clinical visits to the ophthalmologist. All drug costs were market prices...

  15. Patient adherence and reimbursement amount for antidiabetic fixed-dose combination products compared with dual therapy among Texas Medicaid recipients.

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    Cheong, Chelim; Barner, Jamie C; Lawson, Kenneth A; Johnsrud, Michael T

    2008-10-01

    Little is known about the potential for improved adherence with and cost savings of fixed-dose combination therapy (FDCT) products compared with analogous dual therapy for type 2 diabetes mellitus. The objectives of this study were as follows: (1) to describe patient adherence to various oral antidiabetic regimens (ie, dual therapy and FDCT); (2) to determine whether there is a difference in medication adherence between FDCT users and analogous dual-therapy users; and (3) to assess whether there is a difference in reimbursement amounts between an FDCT product and its individual components. This study was a retrospective cohort analysis using the Texas Medicaid prescription claims database. The study subjects included those who used antidiabetic FDCT or dual therapy from August 1, 2000, to July 31, 2004. The identification period of study subjects was between August 1, 2000, and July 31, 2004, including 12 months before and after the index date, so that the overall time frame was from August 1, 1999, through July 31, 2005. Prescription claims were analyzed over a 12-month preindex and 12-month postindex period. Adherence was measured using medication possession ratio (MPR), and regimen costs per tablet were assessed utilizing the index prescription. Overall, 7570 FDCT users and 14,762 dual-therapy users were identified. Regarding the postindex period, FDCT users had 1.8% higher MPR compared with dual-therapy users (78.6% vs 77.2%). Patients who switched from monotherapy to FDCT had a 1.5% decrease in adherence (from 79.7% to 78.5%), whereas those who switched from monotherapy to dual therapy had a 10.0% decrease in adherence (from 83.0% to 74.7%). Those who switched from dual therapy to FDCT had a 12.4% increase in adherence (from 72.7% to 81.7%). Multivariate logistic regression analyses revealed that among preindex monotherapy users, FDCT users were significantly more likely to have higher adherence than dual-therapy users (odds ratio [OR] = 1.867; 95% CI, 1

  16. Efficacy and safety of a fixed combination of tramadol and paracetamol (acetaminophen) as pain therapy within palliative medicine.

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    Husic, Samir; Izic, Senad; Matic, Srecko; Sukalo, Aziz

    2015-02-01

    The goal of the research was to determine the efficacy of a fixed combination of tramadol and paracetamol (acetaminophen) in the treatment of pain of patients with the advanced stage of cancer. A prospective study was conducted at the Center for Palliative Care, University Clinical Center Tuzla, Bosnia and Herzegovina, from January 1(st) to December 31(st) 2013. A total of 353 patients who were treated with a fixed combination of tramadol and acetaminophen (37.5 mg and 325 mg) at the initial dosage 3x1 tablet (112.5 mg tramadol and 975 mg acetaminophen) for pain intensity 4, up to 4x2 tablets (300 mg of tramadol and 2600 mg paracetamol) for pain intensity 7 and 8. If the patient during previous day has two or more pain episodes that required a "rescue dose" of tramadol, increased was the dose of fixed combination tramadol and acetaminophen to a maximum of 8 tablets daily (300 mg of tramadol and 2600 mg paracetamol). Statistical analysis was performed by biomedical software MedCalc for Windows version 9.4.2.0. The difference was considered significant for Pparacetamol). Side effects, in the treatment of pain with a fixed combination tramadol and acetaminophen, were found in 29.18% of patients, with a predominance of nausea and vomiting. Fixed combination of tramadol and acetaminophen can be used as an effective combination in the treatment of chronic cancer pain, with frequent dose evaluation and mild side effects.

  17. EFFICACY OF FIXED COMBINATION OF VALSARTAN, AMLODIPINE AND HYDROCHLOROTHIAZIDE IN COMPLEX THERAPY OF THE PATIENT OF VERY HIGH CARDIOVASCULAR RISK

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    I. M. Sokolov

    2012-01-01

    Full Text Available The high prevalence of arterial hypertension in association with high and very high cardiovascular risk requires widespread use of combined therapy. Current approaches to selection of combination components of antihypertensive drugs are based the efficacy of these drugs proven in multicenter randomized clinical trials. The triple combination of calcium antagonist, angiotensin II receptor blocker and thiazide diuretic is regarded as the best option for combined therapy in patients with arterial hypertension and ischemic heart disease to reduce cardiovascular risk.

  18. COMBINED ANTIHYPERTENSIVE THERAPY IN REAL CLINICAL PRACTICE. FOCUS ON FIXED COMBINATIONS OF ANTIHYPERTENSIVE DRUGS (According to the Data of Outpatient Registries RECVASA and PROFILE

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    S. Yu. Martsevich

    2017-01-01

    Full Text Available On Behalf of the Working Groups of the Registries PROFILE and REСVASA. Working Group of the PROFILE Registry: Akimova A.V., Voronina V.P., Dmitrieva N.A., Zakharova A.V., Zakharova N.A., Zagrebelnyy A.V., Kutishenko N.P., Lerman O.V., Lukina Yu.V., Tolpygina S.N., Martsevich S.Y.Working Group of the RECVASA Registry: Vorobyev A.N., Zagrebelnyy A.V., Kozminsky A.N., Lukina Yu.V., Loukianov M.M., Moseichuk K.A., Nikulina N.N., Pereverzeva K.G., Pravkina E.A., Boytsov S.A., Martsevich S.Yu., Yakushin S.S.Aim. To assess the frequency of prescription of different combinations of the main groups of antihypertensive drugs (AHD and their fixed combinations to patients with arterial hypertension by physicians according to two outpatient registries.Material and methods. Hypertension was diagnosed in 3648 (98.9% patients of the RECVASA registry and in 1230 patients of the PROFILE registry (80.3%. Data on doctor’s prescriptions reflected in the outpatient charts of patients of the both registries were analyzed. The following information of the prescribed antihypertensive therapy was studied in details: AHD, including fixed and free combinations, original and generic AHD. Data on the achievement/non-achievement of target blood pressure (BP level in patients with hypertension were also analyzed.Results. Women were predominated among hypertensive patients of the RECVASA registry, (71.9%. The ratio of men and women was close to 1:1 in the PROFILE registry. Patients of the registry RECVASA were older: the average age was 66.2±12.8 years compared to 63.7±11.4 years in patients of the PROFILE registry, respectively. The majority of patients in the RECVASA registry (61.4% had hypertension of the 3rd degree, patients of the PROFILE registry revealed mostly hypertension of the 2 degree (53.3%. Fixed combinations were prescribed to 14% of patients in the registry of RECVASA and to 16% of patients in the PROFILE registry. Doctors of the PROFILE registry often

  19. Long-term stability of combined rapid palatal expansion-lip bumper therapy followed by full fixed appliances.

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    Ferris, Tyler; Alexander, R G; Boley, Jimmy; Buschang, Peter H

    2005-09-01

    The purpose of this study was to evaluate the long-term postretention stability of rapid palatal expansion-lip bumper therapy followed by full fixed appliances. The sample included 20 treated patients (11 women and 9 men) who were recalled to obtain postretention records. The subjects were out of retention for a minimum of 4 years and an average of 7.9 years. They had begun treatment in the late mixed dentition at a mean age of 11.1 with considerable incisor crowding but, on average, no tooth size-arch length discrepancies. Pretreatment, posttreatment (mean age, 13.6 years), and postretention (mean age, 24.3 years) models were digitized, and the computed measurements were compared with untreated reference data. The majority of treatment increases in maxillary and mandibular arch dimensions were statistically significant (P lip bumper expansion therapy in the late mixed dentition followed by full fixed appliances is an effective form of treatment for patients with up to moderate tooth size-arch length discrepancies.

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

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    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

  1. Fixed-ratio combination therapy with GLP-1 receptor agonist liraglutide and insulin degludec in people with type 2 diabetes

    DEFF Research Database (Denmark)

    Østergaard, Lauge; Frandsen, Christian Seerup; Dejgaard, Thomas Fremming

    2017-01-01

    INTRODUCTION: A fixed combination of basal insulin degludec and glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide (IDegLira; 50 units degludec/1.8 mg liraglutide) has been developed as a once daily injection for the treatment of type 2 diabetes (T2D). In the phase 3a trial programme ......Lira combines the clinical advantages of basal insulin and GLP-1RA treatment, and is a treatment strategy that could improve the management of patients with T2D....... "Dual action of liraglutide and insulin degludec in type 2 diabetes" (DUAL™), five trials of 26 weeks duration and one trial of 32 weeks duration have evaluated the efficacy and safety of IDegLira compared with administration of insulin degludec, insulin glargine, liraglutide alone or placebo. Areas...... groups; however, gastrointestinal side effects were fewer with IDegLira compared with liraglutide treatment alone. A limitation of the DUAL™ development programme is that patients receiving basal insulin doses in excess of 50 units were excluded from the studies. Expert Commentary: In conclusion, IDeg...

  2. [Therapy of Arterial Hypertension in Patients With Chronic Heart Failure and Signs of Chronic Kidney Disease With Fixed Perindopril/Amlodipine Combination].

    Science.gov (United States)

    Borovkova, N Ju; Kuznecova, T E; Borovkov, N N; Kovaleva, G V

    2015-01-01

    to assess efficacy of a fixed combination of perindopril arginine and amlodipine besylate in the treatment of hypertensive patients with chronic heart failure (CHF) and signs of chronic kidney disease (CKD). Persons with CKD (n = 53, age 64.5 ± 8.2 years) were selected from 118 patients with grade 2-3 essential hypertension with CHF. Presence of CKD was confirmed by elevated blood levels of cystatin C and lowered glomerular filtration rate (GFR). Used doses of fixed perindopril/amlodipine combination were 5/5, 5/10, 10/10 mg. Efficacy was assessed after 2 months of therapy on the basis of results of the examination which included clinical blood pressure (BP), BP monitoring, 6-min walk test. Blood levels of creatinine, urea, cystatin C and GFR were also measured. Target BP was achieved in 92.6% of patients. Clinical BP was significantly decreased. Daily average systolic BP decreased by 14.7%, diastolic BP--by 14.4%. Systolic and diastolic BP load also decreased. Clinical condition improved. Tolerance to physical work increased. Level of cystatin C significantly decreased while GFR increased. Fixed perindopril/amlodipine combination produced good therapeutic effect in hypertensive patients with CHF and CKD.

  3. Regulatory requirements for marketing fixed dose combinations.

    Science.gov (United States)

    Jayasheel, B G

    2010-10-01

    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.

  4. Regulatory requirements for marketing fixed dose combinations

    Directory of Open Access Journals (Sweden)

    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.

  5. Twelve-week, randomized, multicenter study comparing a fixed combination of brimonidine-timolol with timolol as therapy adjunctive to latanoprost

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    Fechtner RD

    2011-07-01

    Full Text Available Robert D Fechtner1, Paul Harasymowycz2, Donald R Nixon3, Steven D Vold4, Fiaz Zaman5, Julia M Williams6, David A Hollander61Glaucoma Division, University of Medicine and Dentistry New Jersey, Newark, NJ, USA; 2University of Montreal, Montreal, QC, Canada; 3Royal Victoria Hospital, Barrie, ON, Canada; 4Boozman-Hof Regional Eye Clinic, Rogers, AR, USA; 5Houston Eye Associates, Houston, TX, USA; 6Allergan Inc, Irvine, CA, USAObjective: To evaluate the additive intraocular pressure (IOP-lowering efficacy and safety of fixed-combination brimonidine 0.2%/timolol 0.5% compared with timolol 0.5% at peak and trough effect when used as therapy adjunctive to latanoprost 0.005% in patients with glaucoma or ocular hypertension who require additional IOP lowering.Methods: In this prospective, randomized, multicenter, investigator-masked, parallel-group study, patients were treated with latanoprost monotherapy for at least four weeks prior to baseline. At baseline on latanoprost, patients with IOP ≥21 mmHg in at least one eye were randomized to twice-daily fixed brimonidine-timolol (n = 102 or timolol (n = 102, each adjunctive to latanoprost for 12 weeks. IOP was measured at 8 am and 10 am at baseline, week 6, and week 12 and evaluated in the per protocol population. The primary efficacy endpoint was peak IOP lowering at 10 am, week 12. Safety measures included adverse events.Results: Baseline mean IOP was similar at 10 am in the treatment groups (brimonidine-timolol 23.4 mmHg; timolol 23.0 mmHg. The mean additional reduction from latanoprost-treated baseline IOP was 8.3 mmHg (35.5% with fixed brimonidine-timolol and 6.2 mmHg (27.0% with timolol at 10 am, week 12 (P < 0.001. Patients treated with fixed brimonidine-timolol adjunctive to latanoprost were significantly more likely than patients treated with adjunctive timolol to achieve an IOP <18 mmHg (P = 0.028 and a ≥20% reduction in IOP from baseline (P = 0.047 at both 8 am and 10 am in week 12. Adverse

  6. Efficacy and safety of travoprost 0.004%/timolol 0.5% fixed combination as transition therapy in patients previously on prostaglandin analog monotherapy

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    Costa VP

    2012-05-01

    Full Text Available Vital Paulino Costa1, Hamilton Moreira2, Mauricio Della Paolera3, Maria Rosa Bet de Moraes Silva41Universidade Estadual de Campinas – UNICAMP, São Paulo, 2Universidade Federal do Paraná, Curitiba, 3Santa Casa de Misericórdia de São Paulo, São Paulo, 4Faculdade de Medicina de Botucatu, UNESP, BrazilPurpose: To assess the safety and efficacy of transitioning patients whose intraocular pressure (IOP had been insufficiently controlled on prostaglandin analog (PGA monotherapy to treatment with travoprost 0.004%/timolol 0.5% fixed combination with benzalkonium chloride (TTFC.Methods: This prospective, multicenter, open-label, historical controlled, single-arm study transitioned patients who had primary open-angle glaucoma, pigment dispersion glaucoma, or ocular hypertension and who required further IOP reduction from PGA monotherapy to once-daily treatment with TTFC for 12 weeks. IOP and safety (adverse events, corrected distance visual acuity, and slit-lamp biomicroscopy were assessed at baseline, week 4, and week 12. A solicited ocular symptom survey was administered at baseline and at week 12. Patients and investigators reported their medication preference at week 12.Results: Of 65 patients enrolled, 43 had received prior travoprost therapy and 22 had received prior nontravoprost therapy (n = 18, bimatoprost; n = 4, latanoprost. In the total population, mean IOP was significantly reduced from baseline (P = 0.000009, showing a 16.8% reduction after 12 weeks of TTFC therapy. In the study subgroups, mean IOP was significantly reduced from baseline to week 12 (P = 0.0001 in the prior travoprost cohort (19.0% reduction and in the prior nontravoprost cohort (13.1% reduction. Seven mild, ocular, treatment-related adverse events were reported. Of the ten ocular symptom questions, eight had numerically lower percentages with TTFC compared with prior PGA monotherapy and two had numerically higher percentages with TTFC (dry eye symptoms and ocular

  7. Adherence to a fixed-dose combination of rosiglitazone/glimepiride in subjects switching from monotherapy or dual therapy with a thiazolidinedione and/or a sulfonylurea.

    Science.gov (United States)

    Thayer, Sarah; Arondekar, Bhakti; Harley, Carolyn; Darkow, Theodore E

    2010-05-01

    In 2005, a fixed-dose combination therapy (FDCT) of rosiglitazone maleate and glimepiride became available for treatment of type 2 diabetes mellitus. It is hypothesized that FDCTs increase adherence by decreasing the number of required tablets. To assess changes in medication adherence and hemoglobin A(1c) (A1C) values in subjects switching from monotherapy with either a sulfonylurea or rosiglitazone or dual therapy with both to rosiglitazone/glimepiride FDCT. This retrospective database analysis included subjects with 1 or more prescription fills for rosiglitazone, a sulfonylurea, or rosiglitazone/glimepiride FDCT during the identification period of January 1, 2006, to September 30, 2006. Subjects were grouped according to baseline and follow-up period treatment regimens: sulfonylurea or rosiglitazone monotherapy switched to sulfonylurea and rosiglitazone dual therapy (Mono/Dual), monotherapy to rosiglitazone/glimepiride FDCT (Mono/FDCT), sulfonylurea and rosiglitazone dual therapy in both periods (Dual/Dual), and dual therapy to rosiglitazone/glimepiride FDCT (Dual/FDCT). The medication possession ratio (MPR) was calculated as a measure of adherence. The change in A1C from the baseline period to the follow-up period was assessed for each cohort. The study included 16,490 subjects. From baseline to follow-up, MPR decreased for both the Mono/FDCT cohort and the Mono/Dual cohort, but the magnitude of this decrease was less for the Mono/FDCT cohort (-0.02 vs -0.10; p FDCT cohort compared with the Dual/Dual cohort (+0.10 vs +0.05; p FDCT cohort (-1.08%) and the Mono/Dual cohort (-0.77%). Compared with the Dual/Dual cohort, the Dual/FDCT cohort experienced a greater absolute reduction in A1C (-0.06% vs -0.51%; p = 0.004). The results remained statistically significant in the multivariate model. Switching to rosiglitazone/glimepiride FDCT, in comparison with switching to dual therapy, was associated with improvements in medication adherence and glycemic control.

  8. Rilpivirine/tenofovir/emtricitabine fixed-dose combination is an efficacious and well-tolerated “switch” regimen for patients on therapy

    Directory of Open Access Journals (Sweden)

    D Ward

    2012-11-01

    Full Text Available The rilpivirine/tenofovir/emtricitabine fixed-dose combination (RTE FDC (Complera, Eviplera is a potent convenient, well-tolerated antiretroviral regimen. While it is officially indicated only for treatment-naïve patients, it is attractive for use as a regimen to switch to for patients experiencing toxicities or side effects, or who simply want a regimen with fewer pills. This is a retrospective review of patients who switched to RTE FDC from other antiretroviral regimens in a large HIV specialty private practice. 111 patients were identified who switched to RFE FDC from other regimens who had at least six months follow-up (median 8 months. 44 were previously taking the efavirenz/tenofovir/emtricitabine fixed-dose combination (ETE FDC (Atripla, 24 nevirapine with NRTIs, 16 protease-based regimens, 10 on raltegravir with NRTIs, and 17 on various other regimens. Patients had been on therapy for a median of 6.25 years. 86 patients had an HIV PCR<20 at the time of switch, 21 had low grade positive PCRs (<400 and 4 patients switched after an interruption in therapy with viral loads of 5880–88,000. Median CD4 cell count at the time of switch was 663 (range 142–2244. 14 patients had previously failed treatment and had resistance mutations; 4 with M184V, 5 with K103N, but none with rilpivirine nor tenofovir-specific resistance mutations. One patient discontinued RFE FDC after a single PCR of 520; all others have remained undetectable at most recent visit (91<20, 19<400. Median CD4 cell count on the most recent visit is 656. Creatinine (first visit after switch increased by a mean of 0.04 mg/dl (0.05 in those switching from a non-tenofovir containing regimen, 0.04 in those switching from a tenofovir containing regimen. There was no significant change in LFTs. Mean cholesterol decreased by 18 mg/dl (23 in those switching from ETE FDC, 12 from protease inhibitors, 27 from nevirapine and 2 from raltegravir. Six patients co-infected with hepatitis B

  9. A 4-year retrospective study of add-on therapy to the fixed combination of dorzolamide/timolol for the treatment of POAG

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    Curt Hartleben-Matkin

    2014-04-01

    Full Text Available AIM: To evaluate the long-term response to the fixed combination of dorzolamide/timolol in patients with primary open angle glaucoma (POAG and the addition of other intraocular pressure (IOP lowering medications such as prostaglandin analogs and brimonidine.METHODS: A retrospective, non-randomized, and descriptive clinical study was performed with 182 eyes diagnosed with POAG. Patients were divided into three groups:a group with fixed combination of dorzolamide/timolol only, a second group with prostaglandin analogs plus fixed combination of dorzolamide/timolol, and a third group with the addition of brimonidine to the same fixed combination. IOP data were gathered retrospectively and the differences between groups were calculated.RESULTS: IOP was reduced satisfactorily in all three groups; however, a progressive IOP reduction was noted in the group with the fixed combination plus prostaglandin analogs. In this group, a progressive, significant and more homogeneous response of the reduction was noted in comparison with the other groups.CONCLUSION: IOP reduction was efficacious in all three groups. The addition of prostaglandin analogs showed progressive IOP reduction, progressive response and absence of long-term drift. Brimonidine did not show a significant additive effect.

  10. Efficacy and safety of pioglitazone/metformin fixed-dose combination therapy compared with pioglitazone and metformin monotherapy in treating patients with T2DM.

    Science.gov (United States)

    Perez, Alfonso; Zhao, Zhen; Jacks, Randal; Spanheimer, Robert

    2009-12-01

    Studies have shown that many patients with type 2 diabetes do not achieve optimal glycemic control, and progression of diabetes over time requires more than one pharmacotherapy to achieve glycemic goal. To examine the efficacy and safety of the fixed-dose combination (FDC) of pioglitazone 15 mg and metformin 850 mg versus its individual components in a twice-daily regimen over 24 weeks of treatment in type 2 diabetes patients who were currently not receiving antidiabetes therapy. This was a double-blind, randomized, parallel-group, controlled study. The primary endpoint was change from baseline in hemoglobin A1c (HbA1c) of pioglitazone/metformin FDC therapy compared with pioglitazone and metformin monotherapy. Secondary endpoints included change from baseline in fasting plasma glucose (FPG), fasting insulin, and homeostasis model assessment of insulin resistance (HOMA-IR). Safety and tolerability of pioglitazone/metformin FDC therapy and its individual components were also evaluated. Study limitations to be noted include the early stage of diabetes in these patients, which may be more responsive to treatment, and the 6 month treatment period, which does not provide durability data. ClinicalTrials.gov, NCT00727857. From a baseline HbA1c >8.6%, mean HbA1c decreased the most with pioglitazone/metformin FDC (-1.83%) (P pioglitazone (-0.96%) and metformin (-0.99%) monotherapy, with 63.8% of FDC patients achieving HbA1c pioglitazone- and 38.9% of metformin-treated patients. The decrease from baseline to final visit in FPG was significantly larger in the pioglitazone/metformin FDC group (-39.9 mg/dL) (P pioglitazone/metformin FDC. The pioglitazone/metformin FDC was well tolerated with no unexpected findings in adverse events of special interest, including hypoglycemia, bone fractures, peripheral edema, and cardiac failure. Overall, treatment with pioglitazone/metformin FDC demonstrated greater efficacy than its individual components. The FDC therapy was well tolerated

  11. Efficacy and safety of fixed-dose combination therapy, alogliptin plus metformin, in Asian patients with type 2 diabetes: A phase 3 trial.

    Science.gov (United States)

    Ji, Linong; Li, Ling; Kuang, Jian; Yang, Tao; Kim, Dong-Jun; Kadir, Azidah A; Huang, Chien-Ning; Lee, Douglas

    2017-05-01

    This study evaluated the efficacy and safety of 26 weeks of twice-daily (BID) alogliptin + metformin fixed-dose combination (FDC) therapy in Asian patients with type 2 diabetes. Patients aged 18 to 75 years with hemoglobin A1c (HbA1c) of 7.5% to 10.0% after ≥2 months of diet and exercise and a 4-week placebo run-in were enrolled. Eligible patients were randomized (1:1:1:1) to placebo, alogliptin 12.5 mg BID, metformin 500 mg BID or alogliptin 12.5 mg plus metformin 500 mg FDC BID. The primary endpoint was change in HbA1c from baseline to end of treatment (Week 26). In total, 647 patients were randomized. The least-squares mean change in HbA1c from baseline to Week 26 was -0.19% with placebo, -0.86% with alogliptin, -1.04% with metformin and -1.53% with alogliptin + metformin FDC. Alogliptin + metformin FDC was significantly more effective ( P  metformin alone. The safety profile of alogliptin + metformin FDC was similar to that of the individual components alogliptin and metformin. The study demonstrated that treatment with alogliptin + metformin FDC BID resulted in better glycaemic control than either monotherapy and was well tolerated in Asian patients with type 2 diabetes. © 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

  12. 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

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

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    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.

  14. Evaluation of the Quality of Fixed Dose Combination Anti ...

    African Journals Online (AJOL)

    Evaluation of the Quality of Fixed Dose Combination Anti Tuberculosis Drugs in Public and Private Health Institutions in Lusaka District. ... Almost all areas of the world are affected by the availability of substandard and counterfeit medicines, but mounting evidence shows that the problem is disproportionately severe in ...

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

    African Journals Online (AJOL)

    Esem

    (1/7) of the 2FDC samples were none compliant to the BP 2008 specification for percentage content. One sample of 4FDC had a percentage content of. Evaluation of the Quality of Fixed Dose Combination. Anti Tuberculosis Drugs in Public and Private Health. Institutions in Lusaka District. W Mweemba. University of Zambia ...

  16. 1.Evaluation of the quality of fixed dose combination anti ...

    African Journals Online (AJOL)

    46987.2

    countries, essential and life-saving drugs used to treat infectious diseases such as tuberculosis and malaria are often the drugs under threat. Methodology: This was a cross sectional study whose objective was to determine the quality of 3 types of fixed dose combination (FDC) anti TB drugs namely 4FDC, 3FDC and 2FDC ...

  17. Initial therapy with the fixed-dose combination of sitagliptin and metformin results in greater improvement in glycaemic control compared with pioglitazone monotherapy in patients with type 2 diabetes.

    Science.gov (United States)

    Wainstein, J; Katz, L; Engel, S S; Xu, L; Golm, G T; Hussain, S; O'Neill, E A; Kaufman, K D; Goldstein, B J

    2012-05-01

    To evaluate the efficacy and safety of initial therapy with a fixed-dose combination (FDC) of sitagliptin and metformin compared with pioglitazone in drug-naÏve patients with type 2 diabetes. After a 2-week single-blind placebo run-in period, patients with type 2 diabetes, HbA1c of 7.5-12% and not on antihyperglycaemic agent therapy were randomized in a double-blind manner to initial treatment with a FDC of sitagliptin/metformin 50/500 mg twice daily (N = 261) or pioglitazone 30 mg per day (N = 256). Sitagliptin/metformin and pioglitazone were up-titrated over 4 weeks to doses of 50/1000 mg twice daily and 45 mg per day, respectively. Both treatments were then continued for an additional 28 weeks. From a mean baseline HbA1c of 8.9% in both groups, least squares (LS) mean changes in HbA1c at week 32 were -1.9 and -1.4% for sitagliptin/metformin and pioglitazone, respectively (between-group difference = -0.5%; p metformin vs. pioglitazone (57% vs. 43%, p pioglitazone, sitagliptin/metformin treatment resulted in greater LS mean reductions in fasting plasma glucose (FPG) [-56.0 mg/dl (-3.11 mmol/l) vs. -44.0 mg/dl (-2.45 mmol/l), p metformin vs. pioglitazone. A greater reduction in the fasting proinsulin/insulin ratio and a greater increase in homeostasis model assessment of β-cell function (HOMA-β) were observed with sitagliptin/metformin than with pioglitazone, while greater decreases in fasting insulin and HOMA of insulin resistance (HOMA-IR), and a greater increase in quantitative insulin sensitivity check index (QUICKI) were observed with pioglitazone than with sitagliptin/metformin. Both sitagliptin/metformin and pioglitazone were generally well tolerated. Sitagliptin/metformin led to weight loss (-1.4 kg), while pioglitazone led to weight gain (3.0 kg) (p metformin vs. pioglitazone. The between-group difference in the incidence of hypoglycaemia did not reach statistical significance (8.4 and 4.3% with sitagliptin/metformin and pioglitazone, respectively; p

  18. Combining Clozapine and Talk Therapies.

    Science.gov (United States)

    Mulroy, Kevin

    Clozapine is an antipsychotic medication used in the treatment of schizophrenia. This paper reviews articles concerning clozapine therapy. It considers its benefits and dangers in various situations, and how it can be successfully combined with talk therapies. Studies are reviewed concerning patients in outpatient clinics, partial hospitalization…

  19. How sulfadoxine-pyrimethamine (SP was perceived in some rural communities after phasing out chloroquine (CQ as a first-line drug for uncomplicated malaria in Tanzania: lessons to learn towards moving from monotherapy to fixed combination therapy

    Directory of Open Access Journals (Sweden)

    Nsimba Stephen ED

    2006-01-01

    health workers considered the drug to be good and effective against malaria. Such negative perception towards SP highlights the need to start earlier sensitization and educational campaigns to the rural communities for a new drug program to ensure its success. Messages should clearly state what should be expected from the new drug (Coartem, before its introduction. This is important especially as Tanzania is expected to move towards the expensive but efficacious and effective fixed-combination (Coartem anti-malarial therapy early next year (2006.

  20. The long-term effectiveness of generic adult fixed-dose combination ...

    African Journals Online (AJOL)

    The long-term effectiveness of generic adult fixed-dose combination antiretroviral therapy for HIV-infected Ugandan children. ... Results: From March 2004 to June 2006, 104 children were followed with a median age of 5.4 years, median CD4 cell percent and HIV-1 RNA were 11.0% (IQR 6.7-13.9) and 348,846copies/mL ...

  1. Combination therapy in hypertension: An update

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    Kalra Sanjay

    2010-06-01

    Full Text Available Abstract Meticulous control of blood pressure is required in patients with hypertension to produce the maximum reduction in clinical cardiovascular end points, especially in patients with comorbidities like diabetes mellitus where more aggressive blood pressure lowering might be beneficial. Recent clinical trials suggest that the approach of using monotherapy for the control of hypertension is not likely to be successful in most patients. Combination therapy may be theoretically favored by the fact that multiple factors contribute to hypertension, and achieving control of blood pressure with single agent acting through one particular mechanism may not be possible. Regimens can either be fixed dose combinations or drugs added sequentially one after other. Combining the drugs makes them available in a convenient dosing format, lower the dose of individual component, thus, reducing the side effects and improving compliance. Classes of antihypertensive agents which have been commonly used are angiotensin receptor blockers, thiazide diuretics, beta and alpha blockers, calcium antagonists and angiotensin-converting enzyme inhibitors. Thiazide diuretics and calcium channel blockers are effective, as well as combinations that include renin-angiotensin-aldosterone system blockers, in reducing BP. The majority of currently available fixed-dose combinations are diuretic-based. Combinations may be individualized according to the presence of comorbidities like diabetes mellitus, chronic renal failure, heart failure, thyroid disorders and for special population groups like elderly and pregnant females.

  2. Clinical Aspects of Combination of Aesthetic Fixed Prosthetic Appliances

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    Andrii Biben

    2017-10-01

    Full Text Available The objective of the research was to study the peculiarities of the combination of zirconia and ceramic occlusal surfaces when constructing aesthetic fixed prosthetic appliances. Materials and methods. The study included 70 patients with zirconia and ceramic occlusal surfaces of aesthetic fixed dental prostheses. Group I included 24 patients with a combination of zirconia and ceramic occlusal surfaces. Group II included 30 patients with a combination of ceramic occlusal surfaces. Group III included 16 patients with a combination of zirconia occlusal surfaces. All the patients were observed 12 and 24 months after prosthetic repair. Results. 12 and 24 months after prosthetic repair, the occlusal contact surface area was the largest in Group II (8.18±0.16 mm2 and 9.17±0.1 mm2, respectively. In Group I, where only one occlusive surface was made of zirconium dioxide, significantly reduced levels of abrasion were observed as compared to Group II – 8.07±0.21 mm2 and 8.65±0.23 mm2, respectively. 36 months after denture wearing, in Group III, the smallest contact surface area – 7.84±0.15 mm2as well as the lowest growth of the surface area was observed – 8.07±0.13 mm2. Conclusions. Dental prostheses with at least one ceramic occlusal surface exhibit a strong tendency to abrasion and, consequently, to an increase in the occlusal surface area resulting in an excessive load on prosthetic appliance. Moreover, functional and aesthetic values of prosthetic prosthesis sharply decrease. Therefore, we recommend to produce zirconia occlusal surface or at least to combine the same materials, as it will increase the longevity of prosthetic appliance.

  3. 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

  4. A Fixed Telescopic Prosthesis Designed to Retrieve and Convert to Fixed-Removable Combination Case: A Clinical Report.

    Science.gov (United States)

    Zoidis, Panagiotis; Panagiota, Spyropoulou; Polyzois, Gregory

    2015-06-01

    This clinical report describes a fixed maxillary telescopic dental prosthesis (FTDP) employing milled base metal copings and a metal superstructure veneered with composite resin, for the restoration in a periodontally compromised patient with uncontrolled diabetes. The telescopic prosthesis framework design incorporated occlusal rest seats in key positions along the arch in case of future posterior tooth loss, in order to be converted to fixed - removable combination prosthesis. The mandible was restored with a conventional fixed ceramo-metal dental prosthesis.

  5. Umeclidinium/vilanterol fixed-dose combination for COPD.

    Science.gov (United States)

    Gras, J

    2014-03-01

    Chronic obstructive pulmonary disease (COPD) mortality is projected to increase by more than 30% in the next 10 years without interventions to cut risks, particularly tobacco smoke exposure. Umeclidinium/vilanterol at 62.5/25 μg is the fixed-dose combination of a long-acting antimuscarinic agent and a long-acting β2-adrenoceptor agonist that administered as dry powder by inhalation was developed for the maintenance treatment of COPD. The combination demonstrated its efficacy in phase III studies where the amelioration of lung function translated into subjective symptomatic improvements. Its long-term safety and tolerability were demonstrated in a 52-week study. Last December, umeclidinium/vilanterol 62.5/25 μg combination was approved, as Anoro™ Ellipta™, by the U.S. Food and Drug Administration (FDA) for maintenance treatment of COPD, being the first FDA-approved once-daily treatment for COPD that contains two long-acting bronchodilators in a single inhaler. It has been filed for approval with the European Medicines Agency. Copyright 2014 Prous Science, S.A.U. or its licensors. All rights reserved.

  6. 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

  7. Cross-Over Study Comparing Postprandial Glycemic Increase After Addition of a Fixed-Dose Mitiglinide/Voglibose Combination or a Dipeptidyl Peptidase-4 Inhibitor to Basal Insulin Therapy in Patients with Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Ihana-Sugiyama, Noriko; Yamamoto-Honda, Ritsuko; Sugiyama, Takehiro; Tsujimoto, Tetsuro; Kakei, Masafumi; Noda, Mitsuhiko

    2017-02-28

    BACKGROUND Although the efficacy of combination therapy consisting of basal insulin and oral hypoglycemic agents (OHAs) has been shown, which OHAs are the most efficient remains unclear. MATERIAL AND METHODS Five patients with type 2 diabetes were enrolled and treated with insulin degludec and metformin as a basal therapy. The patients were randomized in a cross-over fashion to receive a combination of mitiglinide (10 mg) and voglibose (0.2 mg) (M+V) 3 times daily or linagliptin (5 mg) (L) once daily for 8 weeks. After 8 weeks, 2 kinds of meal tolerance tests were performed as breakfast on 2 consecutive days. The first breakfast contained 460 kcal (carbohydrates, 49.1%; protein, 15.7%; fat, 35.2%), while the second contained 462 kcal (carbohydrates, 37.2%; protein, 19.6%; fat, 43.2%). Self-monitoring blood glucose levels were measured at 0, 30, 60, and 120 min after the meal tests, and the increase in the postprandial area under the curve (AUC)0-120 min was determined. The HbA1c, glycated albumin, and 1,5-anhydroglucitol (AG) levels were measured, and continuous glucose monitoring was performed. RESULTS The increase in the postprandial AUC0-120 min was significantly smaller in the M+V group than in the L group after both meals. The 24-h average, 24-h standard deviations, 24-h AUC, and mean amplitude of glycemic excursion (MAGE) were similar for both groups and after both meals. The change in 1,5-AG was higher in the M+V group than in the L group. CONCLUSIONS The combination of M+V with basal therapy improved postprandial glucose excursion more effectively than L in T2DM patients.

  8. Asthma control in patients on fixed dose combination evaluated with mannitol challenge test.

    Science.gov (United States)

    Romberg, Kerstin A M; Berggren, Anna-Carin; Bjermer, Leif

    2014-02-01

    Asthma is often difficult to control and it is likely that not all patients are optimally treated. This study aimed to explore asthma control in adults receiving fixed dose combination (FDC) therapy. Control of asthma was assessed using the mannitol challenge test as a monitoring tool to see if this would give additional information compared to the asthma control test (ACT). The study was an open-label, prospective study on 98 adults prescribed with FDC therapies for at least three months. 74 patients considered that their asthma was well controlled. However, 60 patients had a positive mannitol challenge test (PD15 test were included, this increased to 64 patients (65%). Exploratory analysis determined that the spirometry parameters; FEV1/FVC and FEV1% of predicted, were statistically significant predictors of a positive mannitol challenge test. Co-morbid conditions such as concomitant upper airway involvement or eczema did not predict mannitol reactivity. Although most patients rated their asthma as well controlled, many provided a positive mannitol challenge test, suggesting the presence of underlying inflammation, despite treatment with fixed dose combination therapy. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Effects of pioglitazone and metformin fixed-dose combination therapy on cardiovascular risk markers of inflammation and lipid profile compared with pioglitazone and metformin monotherapy in patients with type 2 diabetes.

    Science.gov (United States)

    Perez, Alfonso; Jacks, Randal; Arora, Vipin; Spanheimer, Robert

    2010-12-01

    . Type 2 diabetes mellitus (T2DM) treatment should not increase cardiovascular (CV) risk and at best could provide benefit beyond lowering glucose. Pioglitazone has demonstrated a favorable CV profile relative to other oral antidiabetic drugs (OADs) in outcome and observational studies. This randomized, double-blind, parallel-group controlled study examined circulating biomarkers of CV risk in T2DM patients receiving a fixed-dose combination (FDC) of pioglitazone/metformin compared with the respective monotherapies. Patients with stable glycosylated hemoglobin (HbA(1c) ) for 3 months taking no OADs were treated with pioglitazone 15mg/metformin 850mg FDC twice daily (bid), pioglitazone 15mg bid, or metformin 850mg bid for 24 weeks. FDC and pioglitazone increased high-density lipoprotein cholesterol by 14.20% and 9.88%, respectively, vs an increase of 6.09% with metformin (Pmetformin vs FDC). Triglycerides decreased with all three treatments -5.95%, -5.54% and -1.78%, respectively; P=not significant). FDC and pioglitazone significantly decreased small low-density lipoprotein and increased large low-density lipoprotein particle concentrations. Reductions in high-sensitivity C-reactive protein were greater in the FDC and pioglitazone groups. Increases in adiponectin were significant in the FDC and pioglitazone groups (Pmetformin). Overall, adverse events were not higher with the FDC. Thus, treatment with the FDC resulted in improved levels of CV biomarkers, which were better than or equal to monotherapy. © 2010 Wiley Periodicals, Inc.

  10. A Fixed Telescopic Prosthesis Designed to Retrieve and Convert to Fixed-Removable Combination Case: A Clinical Report

    OpenAIRE

    Zoidis, Panagiotis; Panagiota, Spyropoulou; Polyzois, Gregory

    2015-01-01

    This clinical report describes a fixed maxillary telescopic dental prosthesis (FTDP) employing milled base metal copings and a metal superstructure veneered with composite resin, for the restoration in a periodontally compromised patient with uncontrolled diabetes. The telescopic prosthesis framework design incorporated occlusal rest seats in key positions along the arch in case of future posterior tooth loss, in order to be converted to fixed - removable combination prosthesis. The mandible ...

  11. Curcumin in combined cancer therapy.

    Science.gov (United States)

    Troselj, Koraljka Gall; Kujundzic, Renata Novak

    2014-01-01

    The mechanisms of beneficial preventive and therapeutic effects achieved by traditional and complementary medicine are currently being deciphered in molecular medicine. Curcumin, a yellow-colored polyphenol derived from the rhizome of turmeric (Curcuma longa), influences a wide variety of cellular processes through the reshaping of many molecular targets. One of them, nuclear factor kappa B (NF-κB), represents a strong mediator of inflammation and, in a majority of systems, supports the pro-proliferative features of cancer cells. The application of various anticancer drugs, cytostatics, triggers signals which lead to an increase in cellular NF-κB activity. As a consequence, cancer cells often reshape their survival signaling pathways and, over time, become resistant to applied therapy. Curcumin was shown to be a strong inhibitor of NF-κB activity and its inhibitory effect on NF-κB related pathways often leads to cellular apoptotic response. All these facts, tested and confirmed in many different biological systems, have paved the way for research aimed to elucidate the potential beneficial effects of combining curcumin and various anti-cancer drugs in order to establish more efficient and less toxic cancer treatment modalities. This review addresses certain aspects of NF-κB-related inflammatory response, its role in carcinogenesis and therapy benefits that may be gained through silencing NF-κB by selectively combining curcumin and various anticancer drugs.

  12. Role of triple fixed combination valsartan, amlodipine and hydrochlorothiazide in controlling blood pressure

    Directory of Open Access Journals (Sweden)

    Monica Doménech

    2010-04-01

    monotherapy. In summary, triple-therapy with amlodipine/valsartan/hydrochlorothiazide in a single pill contributes additional advantages to fixed -combinations of two drugs, achieving a greater and more rapid reduction in blood pressure levels in a safe, well-tolerated manner.Keywords: hypertension treatment, antihypertensive fixed-dose triple-therapy, blood pressure control

  13. Clinical Aspects of Combination of Aesthetic Fixed Orthopedic Appliances

    OpenAIRE

    Ozhohan, Z. R.; Biben, A. B.

    2016-01-01

    The article presents the results of examination of 80 patients with aesthetic fixed orthopedic appliances. The state of the occlusal surface of fixed orthopedic appliances as well as the occlusal contact surface area was studied. The occlusal surfaces were made of ceramics and zirconium dioxide. The surface area of occlusal contacts was studied using 3Shape Dental System since computer occlusiography provides the most accurate results. Physical examination indicated a higher level of ceramic ...

  14. 21 CFR 300.50 - Fixed-combination prescription drugs for humans.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Fixed-combination prescription drugs for humans. 300.50 Section 300.50 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE GENERAL Combination Drugs § 300.50 Fixed-combination prescription...

  15. EFFICACY AND SAFETY OF FIXED COMBINATION OF LISINOPRIL AND HYDROCHLOROTHIAZIDE FOR MANAGEMENT OF VASCULAR DISORDERS IN PATIENTS WITH ARTERIAL HYPERTENSION

    Directory of Open Access Journals (Sweden)

    L. A. Haisheva

    2009-01-01

    Full Text Available Aim. To study endothelial disorders and artery elasticity disorders in patients with arterial hypertension (HT, as well as possibility of their correction by lisinopril or by fixed low dose combination of lisinopril and hydrochlorothiazide.Material and methods. 99 patients with HT were included in the study. Patients were randomized into 2 groups. Patients of the 1st group were treated with the fixed low dose combination of lisinopril (5мг and hydrochlorothiazide (12,5 mg. Patients of the 2nd group were treated with lisinopril alone. The amlodipine was added in case of insufficient therapy. Pulse wave velocity was defined by volume sphygmography. Tests for evaluation of microalbuminuria and activity of von Willebrand factor were performed.Results. Endothelium function disorders were observed in a half of the patients with HT aged 60 y.o. and older. The fixed low dose combination of lisinopril and hydrochlorothiazide was more effective than lisinopril monotherapy in target blood pressure achievement. Positive changes of endothelium function indicators were founded in both groups of therapy. This fixed combination had also a good safety profile.Conclusion. Lisinopril alone or in low dose combination with hydrochlorothiazide improves endothelium function and decreases microalbuminuria level in patients with HT and high body mass index.

  16. EFFICACY AND SAFETY OF FIXED COMBINATION OF LISINOPRIL AND HYDROCHLOROTHIAZIDE FOR MANAGEMENT OF VASCULAR DISORDERS IN PATIENTS WITH ARTERIAL HYPERTENSION

    Directory of Open Access Journals (Sweden)

    L. A. Haisheva

    2016-01-01

    Full Text Available Aim. To study endothelial disorders and artery elasticity disorders in patients with arterial hypertension (HT, as well as possibility of their correction by lisinopril or by fixed low dose combination of lisinopril and hydrochlorothiazide.Material and methods. 99 patients with HT were included in the study. Patients were randomized into 2 groups. Patients of the 1st group were treated with the fixed low dose combination of lisinopril (5мг and hydrochlorothiazide (12,5 mg. Patients of the 2nd group were treated with lisinopril alone. The amlodipine was added in case of insufficient therapy. Pulse wave velocity was defined by volume sphygmography. Tests for evaluation of microalbuminuria and activity of von Willebrand factor were performed.Results. Endothelium function disorders were observed in a half of the patients with HT aged 60 y.o. and older. The fixed low dose combination of lisinopril and hydrochlorothiazide was more effective than lisinopril monotherapy in target blood pressure achievement. Positive changes of endothelium function indicators were founded in both groups of therapy. This fixed combination had also a good safety profile.Conclusion. Lisinopril alone or in low dose combination with hydrochlorothiazide improves endothelium function and decreases microalbuminuria level in patients with HT and high body mass index.

  17. NONCHEMICAL DEHYDRATION OF FIXED TISSUE COMBINING MICROWAVES AND VACUUM

    NARCIS (Netherlands)

    KOK, LP; BOON, ME

    A novel histoprocessing method for paraffin and plastic sections is presented in which dehydration of fixed tissue blocks is achieved within 5 minutes by microwaving under vacuum. Exploiting the decrease in boiling temperature under vacuum, we succeed in evaporating liquid molecules in the tissues

  18. The development and optimization of a fixed combination of clindamycin and benzoyl peroxide aqueous gel.

    Science.gov (United States)

    Bucks, Daniel; Sarpotdar, Pramod; Yu, Karen; Angel, Arturo; Del Rosso, James

    2009-07-01

    Fixed combination products of clindamycin 1% (as 1.2% clindamycin phosphate) and benzoyl peroxide (BPO) 5% are commonly used in the treatment of acne vulgaris. Although any given topical acne product may be therapeutically effective, signs and symptoms of cutaneous tolerability may lead to missed applications by the patient, thus limiting adherence to therapy. BPO and other formulation components such as surfactants, preservatives and high levels of organic solvents can cause cutaneous irritation and dryness. BPO irritation is dose-dependent. An approach to optimizing the BPO concentration was undertaken to develop a surfactant- and preservative-free, clindamycin and low concentration (BPO formulation. A 33% reduction in skin irritation was seen when the BPO concentration was halved from 5% to 2.5% (clindamycin-BPO 2.5% gel), maintaining a comparable amount of total BPO delivered to the skin. As a result, clindamycin-BPO 2.5% gel appears to provide efficacy comparable to that of higher concentration (5%) fixed clindamycin-BPO combination products and should optimize patient compliance as a result of the reduction in cutaneous tolerability reactions, including signs of skin irritation or dryness. Clinical studies have shown clindamycin-BPO 2.5% gel to be highly effective with the potential for a more favorable tolerability profile compared to products containing higher concentrations of BPO.

  19. 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

  20. 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

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

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    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

  2. Effect on intraocular pressure of switching from latanoprost and travoprost monotherapy to timolol fixed combinations in patients with normal-tension glaucoma.

    Science.gov (United States)

    Igarashi, Ryoko; Togano, Tetsuya; Sakaue, Yuta; Yoshino, Takaiko; Ueda, Jun; Fukuchi, Takeo

    2014-01-01

    Purpose. To evaluate the effect on intraocular pressure (IOP) of switching from latanoprost and travoprost monotherapy to timolol fixed combinations in Japanese patients with normal-tension glaucoma (NTG). Methods. 27 NTG patients (54 eyes) were compared IOP, superficial punctuate keratitis (SPK) scores, and conjunctival injection scores in eyes treated with prostaglandin (PG) or PG analog/beta-blocker (PG/b) fixed-combination 6 months after the change in therapy. Results. The mean baseline intraocular pressure was 17.4 ± 1.59 mmHg in eyes receiving PG therapy only and 17.4 ± 1.69 mmHg in eyes switched to PG/b. Switching to fixed combination therapy from PG monotherapy, the mean IOP was 13.1 ± 1.79 mmHg (P < 0.001)  (-24.71% reduction from baseline) at 6 months. The mean conjunctival injection score was 0.69 for eyes on PG monotherapy and 0.56 for eyes on fixed combination therapy (P = 0.028). The mean SPK scores were 0.46 and 0.53. This difference was not statistically significant (P = 0.463). Conclusions. Switching from PG monotherapy to PG/b fixed combination therapy for NTG resulted in a greater intraocular pressure reduction than PG alone without increasing the number of instillations.

  3. Effect on Intraocular Pressure of Switching from Latanoprost and Travoprost Monotherapy to Timolol Fixed Combinations in Patients with Normal-Tension Glaucoma

    Directory of Open Access Journals (Sweden)

    Ryoko Igarashi

    2014-01-01

    Full Text Available Purpose. To evaluate the effect on intraocular pressure (IOP of switching from latanoprost and travoprost monotherapy to timolol fixed combinations in Japanese patients with normal-tension glaucoma (NTG. Methods. 27 NTG patients (54 eyes were compared IOP, superficial punctuate keratitis (SPK scores, and conjunctival injection scores in eyes treated with prostaglandin (PG or PG analog/beta-blocker (PG/b fixed-combination 6 months after the change in therapy. Results. The mean baseline intraocular pressure was 17.4±1.59 mmHg in eyes receiving PG therapy only and 17.4±1.69 mmHg in eyes switched to PG/b. Switching to fixed combination therapy from PG monotherapy, the mean IOP was 13.1±1.79 mmHg (P<0.001  (-24.71% reduction from baseline at 6 months. The mean conjunctival injection score was 0.69 for eyes on PG monotherapy and 0.56 for eyes on fixed combination therapy (P=0.028. The mean SPK scores were 0.46 and 0.53. This difference was not statistically significant (P=0.463. Conclusions. Switching from PG monotherapy to PG/b fixed combination therapy for NTG resulted in a greater intraocular pressure reduction than PG alone without increasing the number of instillations.

  4. Combination therapy for type 2 diabetes: dapagliflozin plus metformin.

    Science.gov (United States)

    Tan, Xueying; Hu, Jingbo

    2016-01-01

    Type 2 diabetes (T2D) is a chronic and multifactorial metabolic disease, which brings great threats to public health. The morbidity of T2D keeps growing, and it is estimated that the population with T2D will rise to 552 million throughout the world by 2030. Effective glycemic control in patients is crucial for the treatment of T2D. However, with progressive deterioration of disease, most patients are usually unable to achieve glycemic targets receiving antidiabetic agent monotherapy. In such cases, combination therapy with different mechanisms of antidiabetic agents is highly desired. In addition, combination therapy can provide advantages beyond better glycemic improvement such as reduced incidence of hypoglycemia and cardiovascular events. We reviewed all the published data regarding the fixed-dose combination therapy of dapagliflozin combined with metformin, including complementary mechanism of action, pharmacodynamics, pharmacokinetics, clinical efficacy and safety. The fixed-dose combination of dapagliflozin and metformin exerts synergistic effects based on two antidiabetic agents with complementary mechanisms of action. Rational co-administration of dapagliflozin and metformin provides better glycemic control with potential weight loss and the reduced incidence of hypoglycaemia.

  5. Does desloratadine alter the serum levels of montelukast when administered in a fixed-dose combination?

    Science.gov (United States)

    Cingi, Cemal; Toros, Sema Zer; Ince, Iskender; Ertugay, Cigdem Kalaycik; Gurbuz, M Kezban; Cakli, Hamdi; Erdogmus, Nagehan; Karasulu, Ercument; Kaya, Ercan

    2013-11-01

    The aim of this study was to investigate the serum levels of montelukast when administered alone or in combination with desloratadine. A prospective crossover study. Twenty-three healthy volunteers were investigated in two sessions. Volunteers were given 10 mg of montelukast orally with 250 mL water in the first session. The same subjects were given 10 mg of montelukast in fixed combination with 5 mg desloratadine 10 days after first session. Blood samples were collected 2, 3, and 4 hours after drug administration, and kept at -80°C after both applications. Plasma samples were analyzed for montelukast concentration. Mean concentration values of both groups were not statistically different (P > .05), but the differences were statistically significant according to time (P .05). The absorption rate of montelukast was not altered when administered with desloratadine. This study suggested that desloratadine does not influence the bioavailability of montelukast, and their combination therapy can be used safely. Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

  6. Sumatriptan-naproxen fixed combination for acute treatment of migraine: a critical appraisal

    Directory of Open Access Journals (Sweden)

    Chaouki K Khoury

    2010-01-01

    Full Text Available Chaouki K Khoury, James R CouchDepartment of Neurology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USAAbstract: Nonsteroidal anti-inflammatory drugs (NSAIDs, including naproxen and naproxen sodium, are effective yet nonspecific analgesic and anti-inflammatory drugs, which work for a variety of pain and inflammatory syndromes, including migraine. In migraine, their analgesic effect helps relieve the headache, while their anti-inflammatory effect decreases the neurogenic inflammation in the trigeminal ganglion. This is the hypothesized mechanism by which they prevent the development of central sensitization. Triptans, including sumatriptan, work early in the migraine process at the trigeminovascular unit as agonists of the serotonin receptors (5-HT receptors 1B and 1D. They block vasoconstriction and block transmission of signals to the trigeminal nucleus and thus prevent peripheral sensitization. Therefore, combining these two drugs is an attractive modality for the abortive treatment of migraine. Sumatriptan–naproxen fixed combination tablet (Treximet® [sumatriptan–naproxen] proves to be an effective and well tolerated drug that combines these two mechanisms; yet is far from being the ultimate in migraine abortive therapy, and further research remains essential.Keywords: Treximet®, sumatriptan–naproxen, migraine, treatment

  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. A systematic review of adherence, treatment satisfaction and costs, in fixed-dose combination regimens in type 2 diabetes.

    Science.gov (United States)

    Hutchins, Valerie; Zhang, Bin; Fleurence, Rachael L; Krishnarajah, Girishanthy; Graham, John

    2011-06-01

    Oral antidiabetics have comparable safety and efficacy when used as fixed-dose combination therapies (FDCT) or loose-pill combination therapies (LPCT) for patients with T2DM. To evaluate alternative outcomes to safety and efficacy with FDCT, a systematic review of literature was conducted. Searches of Medline/Embase databases from 1998 to 2009 used predefined terms: 'fixed-dose combination', 'loose-dose combination' and 'diabetes'. Abstracts were reviewed from ISPOR, ADA, and EASD meetings (1998-2009). T2DM studies reporting adherence, patient-reported outcomes, costs, resource use or cost effectiveness were included. Seventeen studies met the search criteria. Seven studies reported adherence. Adherence was 10-13% higher for FDCT than LPCT in patients starting combination therapy. Adherence decreased 1.5% and 10.0% when switching from monotherapy to combination therapy for FDCT and LPCT respectively (p FDCT increased adherence 3.5%-12.4%, while remaining on LPCT changed adherence -1.5% to 5.0% (p FDCT compared with monotherapy or LPCT. Five RCTs reported treatment satisfaction. Four publications reported patients preferred FDCT using the Diabetes Treatment Satisfaction Questionnaire (DTSQ). One publication reported improved satisfaction for one DTSQ subscale. Five abstracts reported economic outcomes. Two abstracts determined patients on FDCT used fewer healthcare resources and had decreased direct monthly healthcare costs versus LPCT. Two cost-effectiveness analyses determined clinical benefits from clinical trials translate into cost savings and increased life expectancy. One budget impact model reported minimal budget impact. (1) There was limited published literature identified in this review. (2) FDCT are oral medications; these findings may only be relevant to those individuals taking an oral antidiabetic therapy. (3) Publication and reporting biases may exist. The published literature suggested that T2DM patients treated with FDCT may have better

  9. Fixed combinations in the management of hypertension: patient perspectives and rationale for development and utility of the olmesartan – amlodipine combination

    Directory of Open Access Journals (Sweden)

    Eduardo Pimenta

    2008-06-01

    Full Text Available Eduardo Pimenta1, Suzanne Oparil21Department of Hypertension and Nephrology, Dante Pazzanese Institute of Cardiology, Sao Paulo, SP, Brazil; 2Vascular Biology and Hypertension Program, University of Alabama at Birmingham, Birmingham, AL, USAbstract: Although the awareness and control of hypertension has increased, only 37% of hypertensive patients in the US achieve the conservative goal of <140/90 mmHg. Achieving optimal blood pressure (BP control is the most important single issue in the management of hypertension, and in most hypertensive patients, it is difficult or impossible to control BP with one drug. Blocking two or more BP regulatory systems provides a more effective and more physiologic reduction in BP, and current guidelines have recommended the use of combination therapy as first-line treatment, or early in the management of hypertension. Fixed combination therapy is an efficacious, relatively safe, and may be cost-effective method of decreasing BP in most patients with essential hypertension. Similar to other combinations, fixed-dose combination tablets containing the dihydropyridine calcium channel blocker amlodipine and the angiotensin II receptor blocker olmesartan bring together two distinct and complementary mechanisms of action, resulting in improved BP control and potential for improved target organ protection relative to either class of agent alone.Keywords: olmesartan – amlodipine, hyptertension, combination therapy

  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. What future for combination therapies?

    NARCIS (Netherlands)

    Kastelein, John

    2003-01-01

    For most patients who require lipid-lowering treatment, statin monotherapy is the appropriate treatment. However, in those patients where statin monotherapy does not produce optimal lipid levels, the combination of a statin with niacin, a bile acid sequestrant, a fibric acid derivative, a

  12. 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

  13. Fixed space maintainers combined with open-face stainless steel crowns.

    Science.gov (United States)

    Yilmaz, Yucel; Kocogullari, Mutlu Elcin; Belduz, Nihal

    2006-05-01

    This study investigates the clinical performance of fixed space maintainers placed on seriously damaged abutment teeth. Crowns were placed on damaged abutment primary teeth. Fixed space maintainers were prepared by using rectangular wire between the window in the facial surface of the crowns and other abutment teeth and were subsequently bonded with a flowable resin composite. This procedure was introduced clinically, and the cases were observed over a period of twelve months. Twenty-seven fixed space maintainers (25 on lower jaw, two on upper jaw) were included in this study. No clinical failure was recorded in any of the cases in the observation time, and the rate of clinical performance was 100%. The study shows the effectiveness of fixed space maintainers combined with stainless steel crowns ("open-face fixed space maintainers") which were placed on primary molar teeth used as abutments in cases with extensive caries and loss of occlusogingival dimension.

  14. Clinical Effectiveness of Using Aesthetic Fixed Prosthetic Appliances with Combined Occlusal Surface

    Directory of Open Access Journals (Sweden)

    Andrii Biben

    2017-06-01

    Conclusions. Aesthetic fixed prosthetic appliances with combined occlusal surface demonstrated high functional and aesthetic characteristics. The use of the USHPS system showed a decisive advantage of milled frameworks and combined occlusal surface over traditional cast ceramic frameworks.The combination of high mechanical, strength and tribological properties of zirconium dioxide and high biological as well as aesthetic properties of ceramic materials helped reveal high clinical characteristics of aesthetic appliances with combined occlusal surface.

  15. 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

  16. Searching for fixed point combinators by using automated theorem proving: A preliminary report

    Energy Technology Data Exchange (ETDEWEB)

    Wos, L.; McCune, W.

    1988-09-01

    In this report, we establish that the use of an automated theorem- proving program to study deep questions from mathematics and logic is indeed an excellent move. Among such problems, we focus mainly on that concerning the construction of fixed point combinators---a problem considered by logicians to be significant and difficult to solve, and often computationally intensive and arduous. To be a fixed point combinator, THETA must satisfy the equation THETAx = x(THETAx) for all combinators x. The specific questions on which we focus most heavily ask, for each chosen set of combinators, whether a fixed point combinator can be constructed from the members of that set. For answering questions of this type, we present a new, sound, and efficient method, called the kernel method, which can be applied quite easily by hand and very easily by an automated theorem-proving program. For the application of the kernel method by a theorem-proving program, we illustrate the vital role that is played by both paramodulation and demodulation---two of the powerful features frequently offered by an automated theorem-proving program for treating equality as if it is ''understood.'' We also state a conjecture that, if proved, establishes the completeness of the kernel method. From what we can ascertain, this method---which relies on the introduced concepts of kernel and superkernel---offers the first systematic approach for searching for fixed point combinators. We successfully apply the new kernel method to various sets of combinators and, for the set consisting of the combinators B and W, construct an infinite set of fixed point combinators such that no two of the combinators are equal even in the presence of extensionality---a law that asserts that two combinators are equal if they behave the same. 18 refs.

  17. Single-day, three-dose treatment with fixed dose combination artesunate/sulfamethoxypyrazine/pyrimethamine to cure Plasmodium falciparum malaria.

    Science.gov (United States)

    Penali, Louis Koné; Jansen, Frans Herwig

    2008-07-01

    Malaria kills approximately 1.5 to 2.7 million people each year. Despite the introduction of artemisinin-based combination therapies (ACTs), the treatment of malaria is hampered by problems such as inadequate efficacy, recrudescence, early re-infection, low patient compliance, and high cost price of drugs. This study tested the hypothesis that the co-formulated fixed dose combination (FDC) artesunate/sulfamethoxypyrazine/pyrimethamine (As/SMP) administered as a 24-hour therapy with a dose interval of 12 hours is as efficacious and safe as the administration of the same drug over 3 days given with a dose interval of 24 hours, for the treatment of uncomplicated Plasmodium falciparum malaria in Ivory Coast. Two hundred and twenty-one patients presenting with uncomplicated P. falciparum malaria were randomly assigned to either one of the two dosing schemes. Treatment efficacy was assessed using the current 28-day World Health Organization protocol, success being determined by absence of recrudescence and parasitemia on day 28. Both treatment regimens were highly efficacious, with a success rate of 100% (111/111) for the 3-day therapy and 99% (109/110) for the 24-hour therapy. Only one patient in the 24-hour therapy group showed late treatment failure. No serious adverse events or significant laboratory abnormalities were seen. The 24-hour therapy is as well tolerated and efficacious as the same medicament administered over 3 days. This low cost and simplified three-pill treatment is certain to improve compliance.

  18. Gene therapy for hemophilia B mice with scAAV8-LP1-hFIX.

    Science.gov (United States)

    Lu, Wei; Zhou, Qingzhang; Yang, Hao; Wang, Hao; Gu, Yexing; Shen, Qi; Xue, Jinglun; Dong, Xiaoyan; Chen, Jinzhong

    2016-06-01

    Hemophilia B is a hemorrhagic disease caused by the deficiency of clotting factor IX (FIX). Gene therapy might be the ultimate strategy for the disease. However, two main problems that should be solved in gene therapy for hemophilia B are immunity and safety. Self-complementary adeno-associated virus serotype 8 (scAAV8), a non-human primate AAV featuring low immunogenicity and high transfection efficiency in liver cells, might be a potential vector for hemophilia B gene therapy. A strong liver-specific promoter-1 (LP1) was inserted and mutant human FIX Arg338Ala was introduced into plasmid scAAV8-LP1 to develop an optimized AAV8 vector that expresses human clotting factor FIX (hFIX). The efficiency of scAAV8-LP1-hFIX administered through normal systemic injection or hydrodynamic injection was compared. A high expression was achieved using hydrodynamic injection, and the peak hFIX expression levels in the 5 × 10(11) and 1 × 10(11) virus genome (vg) cohorts were 31.94% and 25.02% of normal level, respectively, at 60 days post-injection. From the perspective of long-term (200 days) expression, both injection methods presented promising results with the concentration value maintained above 4% of normal plasma. The results were further verified by enzyme-linked immunosorbent assay and activated partial thromboplastin time. Our study provides a potential gene therapy method for hemophilia B.

  19. Fixed combination of insulin and a glucagon-like peptide-1 analog for the treatment of type 2 diabetes, exemplified by insulin degludec and liraglutide

    DEFF Research Database (Denmark)

    Vedtofte, Louise; Knop, Filip K; Vilsbøll, Tina

    2015-01-01

    Insulin therapy in the management of Type 2 diabetes is often postponed and/or not adequately intensified to maintain glycemic control because of the risk of weight gain and hypoglycemia. A fixed combination of the long-acting insulin degludec and liraglutide has recently been accepted by the EMA...

  20. Combined GPS/GLONASS Precise Point Positioning with Fixed GPS Ambiguities

    Science.gov (United States)

    Pan, Lin; Cai, Changsheng; Santerre, Rock; Zhu, Jianjun

    2014-01-01

    Precise point positioning (PPP) technology is mostly implemented with an ambiguity-float solution. Its performance may be further improved by performing ambiguity-fixed resolution. Currently, the PPP integer ambiguity resolutions (IARs) are mainly based on GPS-only measurements. The integration of GPS and GLONASS can speed up the convergence and increase the accuracy of float ambiguity estimates, which contributes to enhancing the success rate and reliability of fixing ambiguities. This paper presents an approach of combined GPS/GLONASS PPP with fixed GPS ambiguities (GGPPP-FGA) in which GPS ambiguities are fixed into integers, while all GLONASS ambiguities are kept as float values. An improved minimum constellation method (MCM) is proposed to enhance the efficiency of GPS ambiguity fixing. Datasets from 20 globally distributed stations on two consecutive days are employed to investigate the performance of the GGPPP-FGA, including the positioning accuracy, convergence time and the time to first fix (TTFF). All datasets are processed for a time span of three hours in three scenarios, i.e., the GPS ambiguity-float solution, the GPS ambiguity-fixed resolution and the GGPPP-FGA resolution. The results indicate that the performance of the GPS ambiguity-fixed resolutions is significantly better than that of the GPS ambiguity-float solutions. In addition, the GGPPP-FGA improves the positioning accuracy by 38%, 25% and 44% and reduces the convergence time by 36%, 36% and 29% in the east, north and up coordinate components over the GPS-only ambiguity-fixed resolutions, respectively. Moreover, the TTFF is reduced by 27% after adding GLONASS observations. Wilcoxon rank sum tests and chi-square two-sample tests are made to examine the significance of the improvement on the positioning accuracy, convergence time and TTFF. PMID:25237901

  1. Ziconotide combination intrathecal therapy: rationale and evidence.

    Science.gov (United States)

    Wallace, Mark S; Rauck, Richard L; Deer, Timothy

    2010-09-01

    Ziconotide is a nonopioid intrathecal analgesic used to manage moderate to severe chronic pain. Although ziconotide is approved in the United States for intrathecal monotherapy only, it is often used in combination with other intrathecal drugs in clinical practice. The need exists for a critical assessment of the currently available published literature on ziconotide combination therapy. This review summarizes and evaluates the publications from preclinical and clinical peer-reviewed experiments that have investigated the safety and effectiveness of ziconotide in combination with a variety of other drugs. Eleven relevant publications were identified through a systematic search of multiple databases. In preclinical studies, additive or synergistic antinociceptive effects were discovered when ziconotide was used in combination with morphine, clonidine, or baclofen; however, no additional antinociceptive effects were observed when bupivacaine was added to ziconotide therapy. Safety data from animal studies revealed that ziconotide did not exacerbate morphine-induced respiratory depression, or clonidine-induced hypotension or bradycardia; however, ziconotide did potentiate morphine-induced hypotension and inhibition of gastrointestinal tract motility. Results from 2 open-label trials indicated that combination ziconotide and morphine therapy produced greater analgesia than was produced by the use of either drug alone. Preliminary support for the use of ziconotide in combination with morphine, baclofen, or hydromorphone was provided by case studies. Although clinical and preclinical studies provide some support for the use of ziconotide in combination with morphine, hydromorphone, clonidine, or baclofen, strong evidence-based data are limited. Controlled, long-term clinical trials are warranted.

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

    Directory of Open Access Journals (Sweden)

    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. Pharmacokinetic Comparison of Inhaled Fixed Combination vs. the Free Combination of Beclomethasone and Formoterol pMDIs in Asthmatic Children

    DEFF Research Database (Denmark)

    Chawes, Bl; Piccinno, A; Kreiner-Møller, Eskil

    2012-01-01

    17MP (active metabolite of BDP) and Formoterol after single inhalation of Foster® pMDI 50/6μg vs. the free combination of BDP and Formoterol pMDIs in asthmatic children. METHODS: 5-11-year-old children inhaled BDP 200μg and Formoterol 24μg as fixed vs. free combination in an open label, randomized, 2......-way crossover single dose study. Blood was collected pre-dose up to 8h post-dose for pharmacokinetic evaluation (AUC(0-t) , AUC(0-∞) , AUC(0-0.5h) , C(max) , t(max) , t(1/2) ). Pharmacodynamics included heart rate, plasma potassium, urinary glucose and cortisol excretion. Peak expiratory flow......-superior after administration of the two actives as fixed vs. the free combination in 5-11-year-old asthmatic children....

  4. Fixed combination of topical brimonidine 0.2% and timolol 0.5% for glaucoma and uncontrolled intraocular pressure

    Directory of Open Access Journals (Sweden)

    Anne J Lee

    2008-10-01

    Full Text Available Anne J Lee1, Peter McCluskey1,21Department of Ophthalmology, Liverpool Hospital, Liverpool, NSW, Australia; 2Faculty of Medicine, University of New South Wales, Randwick, NSW, AustraliaAbstract: Lowering IOP is the most readily modifiable risk factor to delay the development and progression of glaucoma (POAG. The fixed combination of brimonidine tartrate 0.2% and timolol maleate 0.5% (FCBT combines a highly selective α2-adrenergic agonist (brimonidine with a non-selective β-blocker (timolol. FCBT reduces aqueous production and enhances uveoscleral outflow. Concomitant brimonidine and timolol have additive effects on reducing intraocular pressure (IOP. Multi-center randomized control trials have documented superiority of FCBT twice daily on IOP control compared with monotherapy with the individual components, and equal efficacy compared with concomitant therapy. IOP reduction with FCBT versus fixed combination dorzolamide 2% and timolol 0.5% (FCDT was similar in a small study. Other studies (n > 293 evaluating concomitant brimonidine and timolol have shown that it is not inferior to FCDT. However, concomitant brimonidine and timolol administered twice daily was significantly less efficacious in IOP reduction than fixed combination latanoprost 0.005% and timolol 0.5% (FCLT. There are no published studies comparing FCBT with FCLT. The side effect profile for FCBT reflects that of its individual components. FCBT was generally well tolerated, with less ocular side effects than brimondine alone, but more than timolol alone. Documented systemic effects were few, although this could be confounded by selection bias. FCBT is a safe and effective IOP lowering agent for POAG and ocular hypertension.Keywords: brimonidine, timolol, combigan, glaucoma, combination, ocular hypertension

  5. Artificial intelligence in drug combination therapy.

    Science.gov (United States)

    Tsigelny, Igor F

    2018-02-09

    Currently, the development of medicines for complex diseases requires the development of combination drug therapies. It is necessary because in many cases, one drug cannot target all necessary points of intervention. For example, in cancer therapy, a physician often meets a patient having a genomic profile including more than five molecular aberrations. Drug combination therapy has been an area of interest for a while, for example the classical work of Loewe devoted to the synergism of drugs was published in 1928-and it is still used in calculations for optimal drug combinations. More recently, over the past several years, there has been an explosion in the available information related to the properties of drugs and the biomedical parameters of patients. For the drugs, hundreds of 2D and 3D molecular descriptors for medicines are now available, while for patients, large data sets related to genetic/proteomic and metabolomics profiles of the patients are now available, as well as the more traditional data relating to the histology, history of treatments, pretreatment state of the organism, etc. Moreover, during disease progression, the genetic profile can change. Thus, the ability to optimize drug combinations for each patient is rapidly moving beyond the comprehension and capabilities of an individual physician. This is the reason, that biomedical informatics methods have been developed and one of the more promising directions in this field is the application of artificial intelligence (AI). In this review, we discuss several AI methods that have been successfully implemented in several instances of combination drug therapy from HIV, hypertension, infectious diseases to cancer. The data clearly show that the combination of rule-based expert systems with machine learning algorithms may be promising direction in this field. © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  6. Safety and effectiveness of candesartan and candesartan/HCT fixed dose combination in patients with hypertension.

    Science.gov (United States)

    Setiawati, Arini; Pohan, Taufik

    2013-07-01

    to assess the safety and effectiveness of candesartan and candesartan/HCT fixed-dose combination (FDC) in patients with hypertension in daily clinical practice. an open observational study with a 12-week period of treatment. Candesartan tablets of 4 mg, 8 mg, or 16 mg, or candesartan/HCT FDC tablets (16/12.5 mg) were prescribed to adult hypertensive subjects, both treatment-naive patients and previously treated but uncontrolled patients, depending on the physicians' discretion based on his/her judgment on the clinical condition. from a total of 112 treatment-naive patients and 381 previously treated patients eligible for safety analysis, there were only 3 patients with adverse events, and 2 of which were considered possibly related to candesartan (0.41%) and there were no serious adverse events. Both patients were previously treated patients, one patient experienced nausea and the other patient experienced paresthesia. Candesartan and candesartan/HCT were effective in lowering systolic blood pressure (SBP) and diastolic blood pressure (DBP) from baseline at weeks 4, 8, and 12, in both groups, with 26-27 mm Hg decreases in SBP at week 12 and a trend toward a larger reduction in treatment-naive patients than in previously treated patients, although not statistically significant. However, in terms of patients achieving a BP of Candesartan and candesartan/HCT were also effective for patients with long-standing (>4 years) uncontrolled hypertension with previous antihypertensive therapy, which was most commonly calcium channel blockers (became controlled in >50% of all uncontrolled patients). results of this open observational study showed that candesartan and candesartan/HCT were well tolerated and effective in both treatment-naive patients and uncontrolled hypertensive patients with previous antihypertensive treatment.

  7. Fixed-Wing UAVs Flock Control through Cohesion and Repulsion Behaviours Combined with a Leadership

    Directory of Open Access Journals (Sweden)

    Cezary Kownacki

    2016-02-01

    Full Text Available The aim of this paper is to present a novel approach to swarm control of small fixed-wing UAVs, which combines only two flocking behaviours with a leadership feature. In the presented approach, two fundamental rules of Reynolds flocking are applied, i.e., cohesion and repulsion, as the base of a decentralized control of self-organization of the flock. These rules are combined with a leadership feature, which is responsible for a global behaviour of guidance, as in the case of animals. Such a bio-inspired combination allows the achievement of a coherent collective flight of a flock of fixed-wing UAVs without applying formal behaviours of migration and alignment. This highly simplifies an implementation of the algorithm. The presented results include both numerical simulations and experimental flights, which validate the hardware implementation of the approach.

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

    Directory of Open Access Journals (Sweden)

    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

  9. 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

  10. Fixed-combination treatments for intraocular hypertension in Chinese patients – focus on bimatoprost-timolol

    Directory of Open Access Journals (Sweden)

    Fang Y

    2015-05-01

    Full Text Available Yuan Fang,1,* Zhihong Ling,1,* Xinghuai Sun1–4 1Department of Ophthalmology and Visual Science, Eye, Ear, Nose and Throat Hospital, Shanghai Medical College, Fudan University, 2Shanghai Key Laboratory of Visual Impairment and Restoration, 3Key Laboratory of Myopia, Ministry of Health, 4State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Glaucoma is a common eye disease that can lead to irreversible vision loss if left untreated. The early diagnosis and treatment of primary open-angle glaucoma is challenging, and visual impairment in Chinese glaucoma patients is a serious concern. Most of these patients need more than one topical antiglaucoma agent to control their intraocular pressures (IOPs. In the People’s Republic of China, the daily cost of different glaucoma medication varies greatly, and the treatment habits differ throughout the country. Prostaglandin analogs (PGAs are recommended as first-line monotherapy, because of their efficacy and low risk of systemic side effects. Fixed-combination drops, particularly PGA-based fixed combinations, have recently been developed and used in patients with progression or who have failed to achieve their target IOPs. Here, we reviewed the current literature on the use of bimatoprost-timolol fixed combination (BTFC in the People’s Republic of China. BTFC has achieved good efficacy and tolerability in Chinese clinical trials. In addition, BTFC is more cost effective compared with other fixed combinations available in the People’s Republic of China. Fixed-combination drops may offer benefits, such as keeping the ocular surface healthy, convenience of administration, and improvement in long-term adherence and quality of life. Therefore, BTFC has great potential for the treatment of Chinese glaucoma patients. However, the long-term efficacy of BTFC, comparisons

  11. Predictors of additional intraocular pressure reduction in patients changed to latanoprost/timolol fixed combination

    Directory of Open Access Journals (Sweden)

    Nordmann Jean-Philippe

    2010-03-01

    Full Text Available Abstract Background Given the growing number of ocular hypotensive medications available, it is important to be able to predict a positive response to therapy. The purpose of the present study was to identify predictors of an additional 10% intraocular pressure (IOP reduction after 12 weeks of treatment with latanoprost/timolol fixed combination (FC in patients requiring a change in their previous ocular hypotensive medication. Methods This multicenter, open-label, prospective, phase IIIb study included subjects ≥18 years of age with open-angle glaucoma (OAG or ocular hypertension (OHT. Eligible subjects had baseline IOP ≥21 mmHg and insufficient response to current beta-blocker monotherapy. The primary efficacy analysis (logistic regression identified predictors of a positive response after 12 weeks of latanoprost/timolol FC. Results The intent-to-treat (ITT population included 383 subjects treated with ≥1 drop of FC and having ≥1 follow-up IOP assessment. Mean IOP was 22.19 ± 2.16 mmHg at baseline and was reduced by 5.42 ± 2.71 mmHg at study end. In all, 325 (84.9% subjects had a positive response to latanoprost/timolol FC; the response rate was similar across groups: OAG (n = 208; 82.7%; OHT (n = 161; 87.6%; OAG+OHT (n = 14; 85.7%. Higher baseline IOP (odds ratio: 1.284; 95% confidence interval [CI]: 1.101, 1.497; p = 0.0014 and absence of adverse events (odds ratio: 0.318; 95% CI: 0.161, 0.629; p = 0.0010 were significant predictors of positive response. Age, gender, ethnic origin, diagnosis, family history of OAG/OHT, corneal thickness, and concomitant systemic beta-blocker were not significant predictors of a positive response in the ITT analysis. The FC was well tolerated. The most common adverse events were related to the eye and were consistent with known adverse events associated with latanoprost and timolol. Conclusions These results support the use of latanoprost/timolol FC in patients whose IOP is insufficiently controlled

  12. A Masked, Randomized, Phase 3 Comparison of Triple Fixed-Combination Bimatoprost/Brimonidine/Timolol versus Fixed-Combination Brimonidine/Timolol for Lowering Intraocular Pressure

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    Curt Hartleben

    2017-01-01

    Full Text Available Objective. To evaluate the efficacy and safety of triple fixed-combination bimatoprost 0.01%/brimonidine 0.15%/timolol 0.5% (TFC versus dual fixed-combination brimonidine 0.2%/timolol 0.5% (DFC in primary open-angle glaucoma and ocular hypertension. Methods. Patients with intraocular pressure (IOP ≥23 and ≤34 mmHg were randomized to twice-daily TFC or DFC. The primary variable is the change in worse eye mean IOP from baseline at week 12 (modified intent-to-treat (mITT population. Secondary endpoints are mean IOP and mean change from baseline at weeks 1, 2, 4, 8, and 12 (mITT population. TFC superiority was demonstrated if the primary variable favored TFC (p≤0.05. Sensitivity analyses were conducted, and safety was assessed at all visits. Results. TFC (n=93 provided greater IOP reductions from baseline than DFC (n=97 at week 12 (treatment difference, 0.85 mmHg; p=0.028 and all other visits. TFC was also superior to DFC in patients with high baseline IOP (i.e., IOP ≥ 25 mmHg; p≤0.011. Conjunctival hyperemia, ocular irritation, and dry eye were reported more often with TFC (p≤0.016; however, discontinuations for ocular adverse events were similar between treatments. Conclusions. TFC demonstrated IOP-lowering benefits that outweigh the risk of predominantly mild ocular side effects, which may be particularly relevant in patients who require greater IOP lowering to prevent/delay disease progression. This trial is registered with ClinicalTrials.gov registry number: NCT01241240.

  13. 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

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

    Science.gov (United States)

    Bate, Roger; Tren, Richard; Hess, Kimberly; Attaran, Amir

    2009-02-25

    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. 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. 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. The data indicate that FDC-ALU is chemically and physically stable well beyond its stated shelf-life in uncontrolled

  15. Evaluation of brimonidine-timolol fixed combination in patients of primary open-angle glaucoma

    Science.gov (United States)

    Joshi, Sachin R; Akat, Pramod B; Ramanand, Jaiprakash B; Ramanand, Sunita J; Karande, Vitthal B; Jain, Suyog S

    2013-01-01

    The aim of present study was to compare the efficacy and safety of fixed combination of brimonidine and timolol with individual components used as monotherapy in patients of primary open angle glaucoma. Patients were randomly assigned to receive brimonidine or timolol or brimonidine-timolol fixed combination, with 30 patients in each group. The mean reduction in intraocular pressure in brimonidine, timolol, and brimonidine-timolol group were 4.29 ± 1.97 mm Hg, 4.34 ± 1.21 mm Hg, and 5.54 ± 1.87 mm Hg respectively at 2 weeks and 4.86 ± 1.16 mm Hg, 5.42 ± 1.50 mm Hg, and 7.36 ± 2.58 mm Hg respectively at 6 weeks. When values of mean reduction in intraocular pressure were compared between brimonidine-timolol fixed combination with brimonidine and timolol, it was found to be statistically significant (P < 0.05) at 2 weeks and highly significant (0.001) at 6 weeks. The overall frequency of adverse effects was similar in all three groups. PMID:24008808

  16. Evaluation of brimonidine-timolol fixed combination in patients of primary open-angle glaucoma

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    Sachin R Joshi

    2013-01-01

    Full Text Available The aim of present study was to compare the efficacy and safety of fixed combination of brimonidine and timolol with individual components used as monotherapy in patients of primary open angle glaucoma. Patients were randomly assigned to receive brimonidine or timolol or brimonidine-timolol fixed combination, with 30 patients in each group. The mean reduction in intraocular pressure in brimonidine, timolol, and brimonidine-timolol group were 4.29 ± 1.97 mm Hg, 4.34 ± 1.21 mm Hg, and 5.54 ± 1.87 mm Hg respectively at 2 weeks and 4.86 ± 1.16 mm Hg, 5.42 ± 1.50 mm Hg, and 7.36 ± 2.58 mm Hg respectively at 6 weeks. When values of mean reduction in intraocular pressure were compared between brimonidine-timolol fixed combination with brimonidine and timolol, it was found to be statistically significant ( P < 0.05 at 2 weeks and highly significant (0.001 at 6 weeks. The overall frequency of adverse effects was similar in all three groups.

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

    OpenAIRE

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

    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. Signi...

  18. Clinical utility of fixed combinations of sitagliptin–metformin in treatment of type 2 diabetes

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    Green J

    2010-10-01

    Full Text Available Karen Barnard1,2, Mary Elizabeth Cox1, Jennifer B Green1,21Department of Medicine, Division of Endocrinology, Diabetes, Metabolism and Nutrition, Duke University Medical Center, Durham, NC, USA; 2Department of Medicine, Division of Endocrinology, Durham Veterans Affairs Medical Center, Durham, NC, USAAbstract: Adequate glycemic control in type 2 diabetes remains a difficult but achievable goal. The development of new classes of glucose-lowering medications, including in particular the incretin-based therapies, provides an opportunity to utilize combinations of medications which target multiple physiologic abnormalities in type 2 diabetes. Complementary combination therapy with sitagliptin–metformin lowers glucose via enhancement of insulin secretion, suppression of glucagon secretion, and insulin sensitization. Use of this combination in diabetes management will provide a greater degree of glycosylated hemoglobin-lowering than that seen with the use of either drug as monotherapy, is unlikely to cause significant hypoglycemia, and is generally associated with weight loss. The effectiveness, tolerability, and potential cost savings associated with the use of sitagliptin–metformin combination therapy make this an attractive option in diabetes management. The possible beneficial effects of this therapy on beta cell function, as well as its cardiovascular impact, remain inadequately explored but are of significant interest.Keywords: diabetes mellitus, sitagliptin, dipeptidyl peptidase-4, combination therapy

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

    Science.gov (United States)

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

    2010-07-05

    Ibuprofen and paracetamol differ in their mode of action and related therapeutic effects, suggesting that combined administration may offer improved analgesia. Reported here are the results of two studies on the pharmacokinetic properties of a novel ibuprofen (200 mg) and paracetamol (500 mg) fixed-dose combination tablet. Both studies were open-label, randomised studies in healthy volunteers: Study 1 was a four-way crossover, single-dose study; Study 2 was a two-way cross-over, repeat-dose study. Pharmacokinetic parameters for ibuprofen and paracetamol were similar for the combination and monotherapy tablets (values falling within the 80% to 125% acceptable bioequivalence range) except for the rate of absorption of paracetamol from the combination (tmax), which was significantly faster compared with monotherapy (median difference 10 minutes; p ibuprofen from the combination, compared with 0.58 microg x mL(-1) and 9.00 microg x mL-1, respectively, for monotherapy. For paracetamol, mean plasma levels at 10 and 20 minutes were 5.43 microg x mL(-1) and 14.54 microg x mL(-, respectively, for the combination compared with 0.33 microg x mL(-1) and 9.19 microg x mL(-1), respectively, for monotherapy. The rate of absorption of both ibuprofen and paracetamol was significantly delayed when the combination tablet was administered in the fed versus fasted state; median delay was 25 minutes for ibuprofen (p > 0.05) and 55 minutes for paracetamol (p ibuprofen and paracetamol in a fixed-dose combination tablet does not significantly alter the pharmacokinetic profiles of either drug, except for enhancing the rate of paracetamol absorption, offering potential therapeutic benefits in relation to the onset of analgesia. Concentrations of both drugs reached previously reported therapeutic levels when the combination tablet was administrated in the fed or fasted state. Three times daily dosing may offer enhanced therapeutic effect for longer than twice daily dosing.

  20. Combination antiretroviral therapy and cancer risk

    DEFF Research Database (Denmark)

    Borges, Álvaro H

    2017-01-01

    PURPOSE OF REVIEW: To review the newest research about the effects of combination antiretroviral therapy (cART) on cancer risk. RECENT FINDINGS: HIV+ persons are at increased risk of cancer. As this risk is higher for malignancies driven by viral and bacterial coinfections, classifying malignancies...... initiation in reducing cancer risk, understand the relationship between long-term cART exposure and cancer incidence and assess whether adjuvant anti-inflammatory therapies can reduce cancer risk during treated HIV infection....... into infection-related and infection-unrelated has been an emerging trend. Cohorts have detected major reductions in the incidence of Kaposi sarcoma and non-Hodgkin lymphoma (NHL) following cART initiation among immunosuppressed HIV+ persons. However, recent randomized data indicate that cART reduces risk...

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

    Science.gov (United States)

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

    2016-02-01

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

  2. 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.

  3. Infliximab, azathioprine, or combination therapy for Crohn's disease

    DEFF Research Database (Denmark)

    Colombel, Jean Frédéric; Sandborn, William J; Reinisch, Walter

    2010-01-01

    The comparative efficacy and safety of infliximab and azathioprine therapy alone or in combination for Crohn's disease are unknown.......The comparative efficacy and safety of infliximab and azathioprine therapy alone or in combination for Crohn's disease are unknown....

  4. Saxagliptin and Metformin in Fixed Combination for the Treatment of Type 2 Diabetes in Adults

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    Molly G. Minze

    2013-01-01

    Full Text Available Type 2 diabetes affects millions of people worldwide and significantly contributes to morbidity and mortality of those affected by it. Current guidelines recommend individualized treatment regimens following first line metformin therapy. Saxagliptin, a dipeptidyl-peptidase 4 inhibitor, provides a secondary mechanism of action to decrease hyperglycemia when used in combination with metformin. The combination of metformin and saxagliptin has shown improvements in hemoglobin A 1c and fasting plasma glucose in greater efficacy than when either agent is used alone. Adverse effects of combination therapy are similar to when these agents are used individually, and are rated as tolerable by patient satisfaction scores. Overall, the combination use of saxagliptin in addition to metformin is an attractive option for clinicians to use in the treatment of type 2 diabetes.

  5. Ectopic pregnancy treatment by combination therapy

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    Cymbaluk-Płoska Aneta

    2016-01-01

    Full Text Available Detectability of early stages of ectopic pregnancies has increased due to improvements in ultrasonographic and biochemical techniques. Since the patients’ future procreative plans must be taken into consideration when commencing treatment, the goal of this work was to compare the effects of treatment methods and their impact on fertility. The study included 91 patients treated surgically for ectopic pregnancy. The choice of treatment depended on patients’ general condition, ultrasonographic evaluation and serum level of beta-hCG. A combination of laparoscopic and conservative systemic treatment was applied in 70% of cases. More rapid beta-hCG reduction was noted when laparoscopy and intra-oviductal injection of hyperosmolar glucose or methotrexate (MTX were combined with intramuscular administration of MTX at a dose of 50 mg/m2. Follow-up examination of 66 patients revealed that the greatest number of spontaneous pregnancies (48% resulted after this combination therapy. We conclude that this combination treatment is safe and provides satisfactory results in terms of future fertility.

  6. Ectopic pregnancy treatment by combination therapy.

    Science.gov (United States)

    Cymbaluk-Płoska, Aneta; Chudecka-Głaz, Anita; Kuźniak, Sławomir; Menkiszak, Janusz

    2016-01-01

    Detectability of early stages of ectopic pregnancies has increased due to improvements in ultrasonographic and biochemical techniques. Since the patients' future procreative plans must be taken into consideration when commencing treatment, the goal of this work was to compare the effects of treatment methods and their impact on fertility. The study included 91 patients treated surgically for ectopic pregnancy. The choice of treatment depended on patients' general condition, ultrasonographic evaluation and serum level of beta-hCG. A combination of laparoscopic and conservative systemic treatment was applied in 70% of cases. More rapid beta-hCG reduction was noted when laparoscopy and intra-oviductal injection of hyperosmolar glucose or methotrexate (MTX) were combined with intramuscular administration of MTX at a dose of 50 mg/m2. Follow-up examination of 66 patients revealed that the greatest number of spontaneous pregnancies (48%) resulted after this combination therapy. We conclude that this combination treatment is safe and provides satisfactory results in terms of future fertility.

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

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    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.

  8. Clindamycin phosphate 1.2% / tretinoin 0.025%: a novel fixed-dose combination treatment for acne vulgaris.

    Science.gov (United States)

    Ochsendorf, F

    2015-06-01

    The Global Alliance to Improve Outcomes in Acne Group recommends retinoid-based combination therapy as first-line therapy and the preferred treatment approach for almost all acne patients except those with the most severe disease. Clindamycin 1% (as clindamycin phosphate 1.2%)/tretinoin 0.025% (Clin-RA) is a new fixed-dose retinoid-based combination therapy. The aqueous-based gel formulation of Clin-RA was designed to minimize skin irritation and optimize adherence with the therapy. It contains both solubilized and crystalline tretinoin which allows the retinoid to be slowly released onto the skin surface and decreases the potential for cutaneous irritation. A pooled analysis of three pivotal studies involving 4550 acne patients showed that Clin-RA is well tolerated and effective at treating both inflammatory and non-inflammatory acne lesions. The onset of action of Clin-RA is rapid occurring within 2 weeks of treatment initiation. It is not associated with acne flaring or an increase in clindamycin-resistant Propionibacterium acnes counts. Clin-RA is considered as effective as adapalene 0.1%/benzoyl peroxide (BPO) 2.5%, whereas Clin-RA has a more favourable tolerability profile. Clin-RA may be more effective than clindamycin 1%/BPO 5% at treating non-inflammatory acne lesions since the latter does not contain a retinoid to target comedones. Clin-RA is also easy for patients to handle and apply, and has the advantage of not containing BPO which can bleach hair and fabrics. Taken together, the profile of Clin-RA suggests Clin-RA to be a first-line treatment for patients with facial acne. © 2015 European Academy of Dermatology and Venereology.

  9. 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.

  10. Intraocular pressure-lowering effects of commonly used fixed combination drugs with timolol in the management of primary open angle glaucoma

    Directory of Open Access Journals (Sweden)

    Murat Atabey Ozer

    2014-10-01

    Full Text Available AIM:To evaluate intraocular pressure (IOP-lowering effect and ocular tolerability of brimonidine/timolol, dorzolamide/timolol and latanoprost/timolol fixed combination therapies in the management of primary open angle glaucoma.METHODS:Each drug was administered for two months, after which a circadian tonometric curve was recorded using a Goldmann applanation tonometer. Ocular discomfort (conjunctival hyperemia, burning or stinging, foreign body sensation, itching, ocular pain of each eye was assessed by the subject on a standardized ocular discomfort scale.RESULTS:Among the three study groups, there were no significant differences in the mean baseline IOP measurements, mean 2nd mo IOP measurements, and mean (% change of IOPs from baseline. Among the three study groups, there were no significant differences in the mean IOP measurements obtained at circadian tonometric curves at baseline and at two months controls. In sum brimonidine/timolol, dorzolamide/timolol and latanoprost/timolol fixed combination therapies showed similar effects on IOP levels.CONCLUSION:Brimonidine/timolol, dorzolamide/timolol and latanoprost/timolol fixed combination therapies showed similar lowering efficaties on IOP levels whereas there was no any difference between each other.

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

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    N Shafiq

    2016-01-01

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

  12. [The normative combined therapy for recurrent sinusitis].

    Science.gov (United States)

    Peng, Bengang; Sun, Yiqing; Miao, Xutao; Wang, Xin; Li, Wenjun

    2014-06-01

    To assess the treatment outcome after endoscopic sinus surgery (ESS) in patients with recurrent sinusitis and to research which factors could influence the clinical outcome. Endoscopic sinus surgery was performed in 55 patients. The clinical outcome and epithelization of mucosa after ESS were evaluated by Chinese ENT Association criteria. The total cure rate was 81.82%, effective rate was 92.73%. The mean period of epithelization after operation was 13.2 weeks. No serious complication occurred. The treatment efficacy can be greatly improved by the normative combined therapy which include the standard and orderly perioperative treatment ,the overall shape and nasalization of nasal cavity, postoperative follow-up and clearing cav ity after ESS.

  13. Effect of fluorometholone/tetrahydrozoline fixed combination on conjunctival autograft morphology after primary pterygium excision.

    Science.gov (United States)

    Ozgurhan, Engin Bilge; Kara, Necip; Bozkurt, Ercument; Gencer, Baran; Agca, Alper; Alkin, Zeynep; Demirok, Ahmet

    2013-01-01

    To evaluate the effect of a fluorometholone/tetrahydrozoline fixed combination on conjunctival graft morphology after primary pterygium excision. The patients who underwent pterygium excision with conjunctival autograft transplantation were randomized into three groups based on postoperative medications as the fluorometholone/tetrahydrozoline group, fluorometholone group, and dexamethasone group. Conjunctival graft thickness was measured with anterior segment optical coherence tomography. The conjunctival graft hyperemia was evaluated using a high definition external camera. The mean graft thickness was significantly lower in the fluorometholone/tetrahydrozoline group compared with fluorometholone and dexamethasone groups at 2 weeks (P = 0.002 and P = 0.012, resp.) and at 1 month after surgery (P = 0.003 and P = 0.013, resp.). The conjunctival hyperemia score was significantly lower in the fluorometholone/tetrahydrozoline group compared with fluorometholone and dexamethasone groups at 2 weeks (P = 0.000 and P = 0.000, resp.) and at 1 month (P = 0.039 and P = 0.040, resp.). The graft thickness and conjunctival hyperemia score were similar among the groups at 1 week and 3 months (P > 0.05). The findings of the present study revealed that treatment with the fluorometholone/tetrahydrozoline fixed combination may be helpful to decrease graft edema and to achieve better cosmetic appearance at 2 weeks and 1 month after pterygium excision.

  14. Effect of Fluorometholone/Tetrahydrozoline Fixed Combination on Conjunctival Autograft Morphology after Primary Pterygium Excision

    Directory of Open Access Journals (Sweden)

    Engin Bilge Ozgurhan

    2013-01-01

    Full Text Available Purpose. To evaluate the effect of a fluorometholone/tetrahydrozoline fixed combination on conjunctival graft morphology after primary pterygium excision. Methods. The patients who underwent pterygium excision with conjunctival autograft transplantation were randomized into three groups based on postoperative medications as the fluorometholone/tetrahydrozoline group, fluorometholone group, and dexamethasone group. Conjunctival graft thickness was measured with anterior segment optical coherence tomography. The conjunctival graft hyperemia was evaluated using a high definition external camera. Results. The mean graft thickness was significantly lower in the fluorometholone/tetrahydrozoline group compared with fluorometholone and dexamethasone groups at 2 weeks (P=0.002 and P=0.012, resp. and at 1 month after surgery (P=0.003 and P=0.013, resp.. The conjunctival hyperemia score was significantly lower in the fluorometholone/tetrahydrozoline group compared with fluorometholone and dexamethasone groups at 2 weeks (P=0.000 and P=0.000, resp. and at 1 month (P=0.039 and P=0.040, resp.. The graft thickness and conjunctival hyperemia score were similar among the groups at 1 week and 3 months (P>0.05. Conclusion. The findings of the present study revealed that treatment with the fluorometholone/tetrahydrozoline fixed combination may be helpful to decrease graft edema and to achieve better cosmetic appearance at 2 weeks and 1 month after pterygium excision.

  15. 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. Copyright 2016 Prous Science, S.A.U. or its licensors. All rights reserved.

  16. Determinants of virological outcome and adverse events in African children treated with paediatric nevirapine fixed-dose-combination tablets

    NARCIS (Netherlands)

    Bienczak, A.; Denti, P.; Cook, A.; Wiesner, L.; Mulenga, V.; Kityo, C.; Kekitiinwa, A.; Gibb, D.M.; Burger, D.M.; Walker, A.S.; McIlleron, H.

    2017-01-01

    BACKGROUND: Nevirapine is the only nonnucleoside reverse transcriptase inhibitor currently available as a paediatric fixed-dose-combination tablet and is widely used in African children. Nonetheless, the number of investigations into pharmacokinetic determinants of virological suppression in African

  17. Current concepts in combination therapy for the treatment of hypertension: combined calcium channel blockers and RAAS inhibitors

    Directory of Open Access Journals (Sweden)

    Alberto F Rubio-Guerra

    2009-11-01

    Full Text Available Alberto F Rubio-Guerra1, David Castro-Serna2, Cesar I Elizalde Barrera2, Luz M Ramos-Brizuela21Metabolic and Research Clinic, 2Internal Medicine Department, Hospital General de Ticomán SS DF, MéxicoAbstract: Recent guidelines for the management of hypertension recommend target blood pressures <140/90 mmHg in hypertensive patients, or <130/80 mmHg in subjects with diabetes, chronic kidney disease, or coronary artery disease. Despite the availability and efficacy of antihypertensive drugs, most hypertensive patients do not reach the recommended treatment targets with monotherapy, making combination therapy necessary to achieve the therapeutic goal. Combination therapy with 2 or more agents is the most effective method for achieving strict blood pressure goals. Fixed-dose combination simplifies treatment, reduces costs, and improves adherence. There are many drug choices for combination therapy, but few data are available about the efficacy and safety of some specific combinations. Combination therapy of calcium antagonists and inhibitors of the renin-angiotensin-aldosterone system (RAAS are efficacious and safe, and have been considered rational by both the JNC 7 and the 2007 European Society of Hypertension – European Society of Cardiology guidelines for the management of arterial hypertension. The aim of this review is to discuss some relevant issues about the use of combinations with calcium channel blockers and RAAS inhibitors in the treatment of hypertension.Keywords: hypertension, calcium channel blockers, renin-angiotensin-aldosterone system inhibitors, fixed-dose combination, adherence

  18. Role of valsartan, amlodipine and hydrochlorothiazide fixed combination in blood pressure control: an update

    Directory of Open Access Journals (Sweden)

    Maurizio Destro

    2010-04-01

    Full Text Available Maurizio Destro1, Francesca Cagnoni1, Antonio D’Ospina1, Alessandra Rossi Ricci1, Elena Demichele1, Emmanouil Peros1, Augusto Zaninelli2, Paola Preti31Internal Medicine, Ospedale Unificato Broni-Stradella, Stradella (PV, Italy; 2General Medicine, School of Medicine, University of Florence, Florence, Italy; 3Internal Medicine, University of Pavia, Pavia, ItalyAbstract: The treatment of moderate or severe hypertension in most cases requires the contemporaneous use of multiple antihypertensive agents. The most available two-drug combinations have an agent that addresses renin secretion and another one that is statistically more effective in renin-independent hypertension. The practice of combining agents that counteract different mechanisms is the most likely explanation for the fact that most available two-drug combinations have an agent that addresses renin secretion (beta-blocker, angiotensin converting enzyme inhibitor, angiotensin II receptor blocker or direct renin inhibitor and another one that is more effective in renin-independent hypertension (diuretic, dihydropyridine or non-dihydropyridine calcium channel blocker. Based on these considerations, addition of hydrochlorothiazide to the combination of an antagonist of the renin-angiotensin system with a calcium channel blocker would constitute a logical approach. Inclusion of a diuretic in the triple combination is based on the evidence that these agents are effective and cheap, enhance the effect of other antihypertensive agents, and add a specific effect to individuals with salt-sensitivity of blood pressure. The benefit of triple combination therapy with amlodipine, valsartan and hydrochlorothiazide over its dual component therapies has been demonstrated, and the use of a single pill will simplify therapy resulting in better blood pressure control.Keywords: valsartan, amlodipine, hydrochlorothiazide, HCTZ, blood pressure, hypertension

  19. [Estimation of antihypertension efficiency and use of fixed combination perindopril+amlodipin by uncontrollable hypertension patients within the limits of routine treatment].

    Science.gov (United States)

    Ishmurzin, G P

    2011-01-01

    The results of observational investigation by prescription of the fixed combination perindopril + amlodipin produced by to the uncontrollable hypertension patients by the previous therapy are described in the given article. In Kazan population 50 patients at the age of 32 to 92 with essential hypertension having blood pressure level of 140/90 mm/hg. Were included into the investigation. Before these patients took different groups of antihypertension preparation (including perindopril). The preparation was prescribed in different fixed dosage depending on duration of hypertension, quantity of taken hypertension groups of preparations and blood pressure level. Then during 1, 2, 3 months of treatment the physician had the possibility to determine the dosage necessary to prescribe. The prescription of perindopril in combination with amlodipin during 3 months led to certain lowering of systolic and diastolic arterial pressure for 38.2 and 11.6 mm/hg accordingly and 80% of patients had the required pressure level of (antihypertension therapy till the end of observation. As a result, the investigation confirmed the high efficiency, good perception, improvement of patient compliance for treatment by prescribing the fixed combination perindopril + amlodipin.

  20. Molecular insight into atypical instability behavior of fixed-dose combination containing amlodipine besylate and losartan potassium.

    Science.gov (United States)

    Handa, Tarun; Jhajra, Shalu; Bhagat, Shweta; Bharatam, P V; Chakraborti, Asit K; Singh, Saranjit

    2017-03-20

    Combination therapy with the use of fixed-dose combinations (FDCs) is evincing increasing interest of prescribers, manufacturers and even regulators, evidently due to the primary benefit of improved patient compliance. However, owing to potential of drug-drug interaction, FDCs require closer scrutiny with respect to their physical and chemical stability. Accordingly, the purpose of the present study was to explore stability behavior of a popular antihypertensive combination of amlodipine besylate (AML) and losartan potassium (LST). Physical mixtures of the two drugs and multiple marketed formulations were stored under accelerated conditions of temperature and humidity (40°C/75% RH) in a stability chamber and samples were withdrawn after 1 and 3 months. The physical changes were observed visibly, while chemical changes were monitored by HPLC employing a method that could separate the two drugs and all other components present. The combination revealed strong physical instability and also chemical degradation of AML in the presence of LST. Interestingly, three isomeric interaction products of AML were formed in the combination, which otherwise were reported in the literature to be generated on exposure of AML free base above its melting point. The same unusual products were even formed when multiple marketed FDCs were stored under accelerated conditions outside their storage packs. However, these were absent when AML alone was stored in the same studied conditions. Therefore, reasons for physical and chemical incompatibility and the mechanism of degradation of AML in the presence of LST were duly explored at the molecular level. The outcomes of the study are expected to help in development of stable FDCs of the two drugs. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Switching from latanoprost to fixed-combination latanoprost-timolol: a 21-day, randomized, double-masked, active-control study in patients with glaucoma and ocular hypertension.

    Science.gov (United States)

    Olander, Kenneth; Zimmerman, Thom J; Downes, Nina; Schoenfelder, John

    2004-10-01

    Approximately 40% of patients with glaucoma are concomitantly prescribed >or=2 different intraocular pressure (IOP)-lowering medications. An effective and well-tolerated fixed combination of agents requiring once-daily instillation may improve patient compliance. The purpose of this study was to compare the efficacy and safety profile of the fixed combination latanoprost 0.005% + timolol maleate 0.5% QD with those of latanoprost 0.005% monotherapy QD in patients whose elevated IOP (>or=21 mm Hg) was inadequately controlled by latanoprost. This 21-day, randomized, double-masked, active-control study was conducted at 49 study sites in Argentina, Brazil, Colombia, Mexico, Peru, the United States, and Venezuela. Adults with glaucoma or ocular hypertension who had failed to reach an IOP of or=2 mm Hg from the baseline level on day 21. Proportions of patients demonstrating IOP decreases >or=3, >or=4, or >or=5 mm Hg from the baseline level and of patients reaching an 10P vs 51.4%, respectively; P or=3, >or=4, or >or=5 mm Hg (for each target level, P vs latanoprost group) or final IOP 18 mm Hg (fixed -combination, 35.1%; latanoprost, 17.8%; P < 0.001). Both treatments were well tolerated. Similar proportions of patients in the fixed-combination and latanoprost groups reported at least 1 treatment-emergent AE (10.9% and 12.1%, respectively). In this selected population of patients with an inadequate initial IOP response to latanoprost, switching to fixed-combination latanoprosttimolol resulted in a greater decrease in IOP and similar tolerability compared with continuing latanoprost therapy.

  2. Black hairy tongue with a fixed dose combination of olanzapine and fluoxetine.

    Science.gov (United States)

    Jhaj, Ratinder; Gour, Pushp Raj; Asati, Dinesh Prasad

    2016-01-01

    Black hairy tongue (BHT) is a benign disease characterized by elongated filiform lingual papillae, with a carpet-like appearance of the dorsum of the tongue. It is has been reported to occur with a prevalence ranging from 0.6% to 11.3%. Although its etiology is not fully understood, BHT may be triggered by smoking, excessive coffee or black tea drinking, poor oral hygiene, trigeminal neuralgia, general debilitation, dry mouth as well as certain drugs. We present here a case of a patient with psychosis, depression, and benign prostatic hyperplasia, who developed BHT following treatment with a fixed dose combination (FDC) of olanzapine and fluoxetine and recovered within 3 months after withdrawal of treatment with FDC.

  3. 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

  4. Hadron cancer therapy complex using nonscaling fixed field alternating gradient accelerator and gantry design

    Directory of Open Access Journals (Sweden)

    E. Keil

    2007-05-01

    Full Text Available Nonscaling fixed field alternating gradient (FFAG rings for cancer hadron therapy offer reduced physical aperture and large dynamic aperture as compared to scaling FFAGs. The variation of tune with energy implies the crossing of resonances during acceleration. Our design avoids intrinsic resonances, although imperfection resonances must be crossed. We consider a system of three nonscaling FFAG rings for cancer therapy with 250 MeV protons and 400   MeV/u carbon ions. Hadrons are accelerated in a common radio frequency quadrupole and linear accelerator, and injected into the FFAG rings at v/c=0.1294. H^{+}/C^{6+} ions are accelerated in the two smaller/larger rings to 31 and 250  MeV/68.8 and 400   MeV/u kinetic energy, respectively. The lattices consist of doublet cells with a straight section for rf cavities. The gantry with triplet cells accepts the whole required momentum range at fixed field. This unique design uses either high-temperature superconductors or superconducting magnets reducing gantry magnet size and weight. Elements with a variable field at the beginning and at the end set the extracted beam at the correct position for a range of energies.

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

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    O. Awodele

    2012-01-01

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

  6. 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

  7. Comparative effects of a fixed Polypodium leucotomos/Pomegranate combination versus Polypodium leucotomos alone on skin biophysical parameters.

    Science.gov (United States)

    Emanuele, Enzo; Bertona, Marco; Biagi, Marco

    2017-02-01

    Polypodium leucotomos extract is a commonly used systemic photoprotective agent. In an exploratory fashion, the current study aimed to compare the effects of oral supplementation with a fixed Polypodium leucotomos/pomegranate combination (PPmix®) versus Polypodium leucotomos alone (Fernblock®) on skin biophysical parameters of Caucasian adults. Forty healthy adult volunteers (20 males and 20 females; mean age: 37.2±5.5 years) were randomized in a 1:1 fashion to a fixed Polypodium leucotomos/pomegranate combination (480 mg/day; n=20) or Polypodium leucotomos alone (480 mg/day; n=20) for 3 months. Six skin biophysical parameters (skin sebum content, hydration, transepidermal water loss [TEWL], erythema index, melanin index, and elasticity) were measured at baseline and after 3 months by personnel blinded to participant allocation. At the end of the study, hydration and elasticity were significantly improved and TEWL was reduced in both groups, without significant intergroup differences. The erythema index was decreased by both treatments, although the fixed Polypodium leucotomos/pomegranate combination was significantly more effective. Finally, melanin index and skin sebum content were reduced by the fixed Polypodium leucotomos/pomegranate combination, whereas Polypodium leucotomos alone did not affect them. Our results suggest that a fixed Polypodium leucotomos/pomegranate combination provides a greater improvement of skin biophysical parameters compared to Polypodium leucotomos alone in adult Caucasians. Our findings may have implications for optimizing systemic skin photoprotection and beautification strategies.

  8. Therapeutic cancer vaccines in combination with conventional therapy

    DEFF Research Database (Denmark)

    Andersen, Mads Hald; Junker, Niels; Ellebaek, Eva

    2010-01-01

    The clinical efficacy of most therapeutic vaccines against cancer has not yet met its promise. Data are emerging that strongly support the notion that combining immunotherapy with conventional therapies, for example, radiation and chemotherapy may improve efficacy. In particular combination...

  9. Combination therapy in the management of pulmonary arterial hypertension.

    Science.gov (United States)

    Buckley, M S; Staib, R L; Wicks, L M

    2013-05-01

    Pulmonary arterial hypertension (PAH) is a progressive disease without a cure, which can lead to right heart failure and death. Over the past decades, several therapeutic advances have been developed for the management of PAH. Although these agents have demonstrated clinical safety and efficacy, some patients may require additional drug therapy due to a lack of response or disease progression. The purpose of this review was to evaluate the safety and efficacy of various combination PAH therapies. A systematic search was conducted using the MEDLINE database (1966 and June 2012) for relevant clinical studies. Searches were limited to English, human and clinical trial using the terms sildenafil, tadalafil, vardenafil, phosphodiesterase inhibitor, prostacyclin, prostaglandin, epoprostenol, treprostinil, iloprost, beraprost, endothelin receptor antagonist, bosentan, ambrisentan, sitaxsentan and pulmonary hypertension. Overall, 22 studies met inclusion criteria. Overall, the majority of trials demonstrated clinical efficacy in improving functional class, reducing pulmonary pressure, or increasing exercise capacity. Most trials were uncontrolled with small sample sizes investigating the acute effects of combination therapy and lacking long-term clinical outcomes. Adjunctive therapy was well tolerated by most patients. Overall, combination therapy is relatively safe and well tolerated. Published guidelines provide evidence-based recommendations for monotherapy. However, suggestions for combination therapy in refractory PAH patients are lacking. Several studies evaluating several combination therapies have been published. The preferred combination treatment among several PAH drug therapies remain controversial. Therefore, clinicians should consider ease of administration, cost, and tolerability when choosing specific combination therapies. Combination therapy appears promising for patients who are refractory to treatment or whose disease progression is not well controlled

  10. Patient satisfaction with fixed-combination bimatoprost/timolol ophthalmic solution: a survey study in patients with glaucoma in China

    Directory of Open Access Journals (Sweden)

    Sun XH

    2017-04-01

    Full Text Available Xinghuai Sun,1,2 Mingkai Lin,3 Xuanchu Duan,4 Chun Zhang,5 Jian Ming6 1Eye, Ear, Nose and Throat Hospital, Shanghai Medical College, Fudan University, Shanghai, 2Key Laboratory of Myopia, Ministry of Health (Fudan University, and Shanghai Key Laboratory of Visual Impairment and Restoration (Fudan University, Shanghai, 3Zhongshan Ophthalmic Center, Guangzhou, 4The Second Xiangya Hospital of Central South University, Changsha, 5Peking University Third Hospital, Beijing, 6Allergan plc, Shanghai, People’s Republic of China Background: Poor adherence to treatment is a problem in glaucoma, and patient dissatisfaction with topical glaucoma medication is a barrier to adherence. The objective of this study was to evaluate glaucoma patients’ satisfaction with fixed-combination bimatoprost/timolol ophthalmic solution (BTFC. Methods: This observational, multicenter study was conducted in China in adults with glaucoma treated with BTFC for 1–3 months. Five hundred patients answered a questionnaire concerning their demographic characteristics, history of glaucoma and topical glaucoma treatment, and use of BTFC. The primary endpoint was patient satisfaction with BTFC assessed on a 10-point scale (1= very dissatisfied, 10= very satisfied.Results: Patients received BTFC alone (65% or with other treatments (35%, most commonly a carbonic anhydrase inhibitor. Most patients (87% used BTFC as a replacement for other medication, usually a β-blocker or prostaglandin analog; 13% received BTFC as add-on treatment. Key reasons for initiating BTFC therapy were poor efficacy of previous treatment (72% of patients and side effects of previous treatment (32% of patients. Most patients agreed or very much agreed that BTFC provided better control of intraocular pressure (85% of patients, had a simpler administration (87% of patients, and was associated with better tolerance and comfort (82% of patients compared with their previous treatment. Mean satisfaction scores were

  11. Fluticasone propionate/formoterol fumarate in fixed-dose combination for the treatment of asthma.

    Science.gov (United States)

    Price, David; Hillyer, Elizabeth V

    2014-06-01

    A new combination inhaler containing fluticasone, a potent inhaled corticosteroid (ICS), and formoterol, a long-acting β-agonist (LABA) with rapid onset and sustained bronchodilator effect, has been approved for treatment of persistent asthma in patients ≥12 years of age requiring combination ICS-LABA therapy. The fluticasone/formoterol combination, delivered via pressurized metered-dose inhaler and available in three dose strengths, has demonstrated a good safety and tolerability profile in trials of up to 1 year. The efficacy of fluticasone/formoterol is greater than that of fluticasone or formoterol alone and noninferior to that of fluticasone/salmeterol and budesonide/formoterol in tightly controlled 8-12-week clinical trials. Advantages of the fluticasone/formoterol combination aerosol include rapid onset of bronchodilation, an attribute preferred by patients, and emission of a high fine-particle fraction that is consistent at different flow rates, which may aid consistency of delivery (given patient variability in inhalation maneuvers) and provide real-life benefits.

  12. What's next after metformin? focus on sulphonylurea: add-on or combination therapy

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    Lim PC

    2015-09-01

    Full Text Available Introduction: The pathophysiology of type 2 diabetes (T2DM mainly focused on insulin resistance and insulin deficiency over the past decades. Currently, the pathophysiologies expanded to ominous octet and guidelines were updated with newer generation of antidiabetic drug classes. However, many patients had yet to achieve their target glycaemic control. Although all the guidelines suggested metformin as first line, there was no definite consensus on the second line drug agents as variety of drug classes were recommended. Objectives: The aim of this review was to evaluate the drug class after metformin especially sulphonylurea and issues around add-on or fixed dose combination therapy. Methods: Extensive literature search for English language articles, clinical practice guidelines and references was performed using electronic databases. Results: Adding sulphonylurea to metformin targeted both insulin resistance and insulin deficiency. Sulphonylurea was efficacious and cheaper than thiazolidinedione, dipeptidyl peptidase-4 inhibitor, glucagon-like peptide 1 analogue and insulin. The main side effect of sulphonylurea was hypoglycaemia but there was no effect on the body weight when combining with metformin. Fixed dose sulphonylurea/metformin was more efficacious at lower dose and reported to have fewer side effects with better adherence. Furthermore, fixed dose combination was cheaper than add-on therapy. In conclusion, sulphonylurea was feasible as the second line agent after metformin as the combination targeted on two pathways, efficacious, cost-effective and had long safety history. Fixed dose combination tablet could improve patient’s adherence and offered an inexpensive and more efficacious option regardless of original or generic product as compared to add-on therapy.

  13. ORGANOPROTECTIVE EFFECTS OF THE FIXED COMBINATION OF ANGIOTENSIN-CONVERTING ENZYME INHIBITOR LISINOPRIL AND DIURETIC HYDROCHLOROTHIAZIDE

    Directory of Open Access Journals (Sweden)

    E. A. Ryabikhin

    2009-01-01

    Full Text Available Aim. To compare the antihypertensive and metabolic effects of combined therapy (carvedilol reception and «School of the hypertensive patient» with these of the carvedilol monotherapy in young patients with arterial hypertension (HT of 1-2 degrees with overweight and obesity.Material and methods. 63 out-patients with HT of 1-2 degrees (aged 18-27 y.o. with overweight and obesity were included in the open parallel randomized clinical preventive trail. Patients wеre randomized into 2 groups. All hypertensive patients received the carvedilol (Vedicardol, Sintez, Russia 25 mg daily. Carvedilol dose was enlarged twice in case of insufficient antihypertensive effect. Patients of the main group (n=32 also passed through the special educational program «School for hypertensive patients». Changes in blood pressure (BP level, body mass index, biochemical markers and risk factors were evaluated initially and in 24 weeks of therapy.Results. Patients of the main group had more significant risk factor manifestations decrease than in group of comparison. More significant body mass index decrease was also observed in the main group in comparison with group of comparison: from 32,5±0,4 to 26,4±0,7 kg/m2 (p<0,01 and from 31,8±0,8 to 28,9±1,18 kg/m2 (p<0,05, respectively. In patients of the main group systolic and diastolic BP decreased by 20,1% and 25,6%, respectively, wile in patients of the group of comparison – by 18,9% and 26%, respectively.Conclusion. It is reasonable to combine carvedilol therapy with special training in the young hypertensive patients with overweight and obesity.

  14. ORGANOPROTECTIVE EFFECTS OF THE FIXED COMBINATION OF ANGIOTENSIN-CONVERTING ENZYME INHIBITOR LISINOPRIL AND DIURETIC HYDROCHLOROTHIAZIDE

    Directory of Open Access Journals (Sweden)

    E. A. Ryabikhin

    2016-01-01

    Full Text Available Aim. To compare the antihypertensive and metabolic effects of combined therapy (carvedilol reception and «School of the hypertensive patient» with these of the carvedilol monotherapy in young patients with arterial hypertension (HT of 1-2 degrees with overweight and obesity.Material and methods. 63 out-patients with HT of 1-2 degrees (aged 18-27 y.o. with overweight and obesity were included in the open parallel randomized clinical preventive trail. Patients wеre randomized into 2 groups. All hypertensive patients received the carvedilol (Vedicardol, Sintez, Russia 25 mg daily. Carvedilol dose was enlarged twice in case of insufficient antihypertensive effect. Patients of the main group (n=32 also passed through the special educational program «School for hypertensive patients». Changes in blood pressure (BP level, body mass index, biochemical markers and risk factors were evaluated initially and in 24 weeks of therapy.Results. Patients of the main group had more significant risk factor manifestations decrease than in group of comparison. More significant body mass index decrease was also observed in the main group in comparison with group of comparison: from 32,5±0,4 to 26,4±0,7 kg/m2 (p<0,01 and from 31,8±0,8 to 28,9±1,18 kg/m2 (p<0,05, respectively. In patients of the main group systolic and diastolic BP decreased by 20,1% and 25,6%, respectively, wile in patients of the group of comparison – by 18,9% and 26%, respectively.Conclusion. It is reasonable to combine carvedilol therapy with special training in the young hypertensive patients with overweight and obesity.

  15. Combining Immunotherapy with Standard Glioblastoma Therapy

    Science.gov (United States)

    This clinical trial is testing standard therapy (surgery, radiation and temozolomide) plus immunotherapy with pembrolizumab with or without a cancer treatment vaccine for patients with newly diagnosed glioblastoma, a common and deadly type of brain tumor.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. 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.

  18. The role of combination therapy in managing pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Hossein-Ardeschir Ghofrani

    2014-12-01

    Full Text Available Pulmonary arterial hypertension (PAH is a complex, progressive disease with several pathobiological mechanisms, including the endothelin, nitric oxide and prostacyclin pathways. Current treatments for PAH target one of these pathways and, in more severe cases or instances of disease worsening, may be combined with a view to target multiple pathways in parallel. Treatment combination is performed sequentially (as an intensification from initial monotherapy or upfront (use of two or more therapies in treatment-naı¨ve patients. Whilst combination therapy has been historically considered to be an option for the treatment of PAH, supporting evidence was typically limited to expert opinion, clinical experience and registry data. Data from randomised controlled trials on sequential combination therapy in particular has grown in recent years, resulting in a change in the level of recommendations in the latest update to the PAH treatment algorithm. However, short-term trials have shown inconsistent results, and have not been powered to assess morbidity/mortality outcomes. More recent data from long-term trials suggest a potential clinical benefit associated with sequential combination therapy. In this review we will introduce the concept of combination therapy, consider the latest evidence for both sequential and upfront combination therapy, and discuss additional considerations when initiating combination therapy in clinical practice.

  19. Effect of Combination Therapy on Joint Destruction in Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Graudal, N.; Hubeck-Graudal, T.; Tarp, S.

    2014-01-01

    Background: Despite significant cost differences, the comparative effect of combination treatments of disease modifying anti-rheumatic drugs (DMARDs) with and without biologic agents has rarely been examined. Thus we performed a network meta-analysis on the effect of combination therapies...... on progression of radiographic joint erosions in patients with rheumatoid arthritis (RA). Methods and Findings: The following combination drug therapies compared versus single DMARD were investigated: Double DMARD: 2 DMARDs (methotrexate, sulfasalazine, leflunomide, injectable gold, cyclosporine, chloroquine...

  20. Esomeprazole and aspirin fixed combination for the prevention of cardiovascular events.

    Science.gov (United States)

    Sylvester, Katelyn W; Cheng, Judy Wm; Mehra, Mandeep R

    2013-01-01

    Low dose aspirin therapy plays a fundamental role in both the primary and secondary prevention of cardiovascular events. Although the evidence using low dose aspirin for secondary prevention is well-established, the decision to use aspirin for primary prevention is based on an evaluation of the patient's risk of cardiovascular events compared to their risk of adverse events, such as bleeding. In addition to the risk of bleeding associated with long term aspirin administration, upper gastrointestinal side effects, such as dyspepsia often lead to discontinuation of therapy, which places patients at an increased risk for cardiovascular events. One option to mitigate adverse events and increase adherence is the addition of esomeprazole to the medication regimen. This review article provides an evaluation of the literature on the concomitant use of aspirin and esomeprazole available through February 2013. The efficacy, safety, tolerability, cost effectiveness, and patient quality of life of this regimen is discussed. A summary of the pharmacokinetic and pharmacodynamic interactions between aspirin and esomeprazole, as well as other commonly used cardiovascular medications are also reviewed. The addition of esomeprazole to low dose aspirin therapy in patients at high risk of developing gastric ulcers for the prevention of cardiovascular disease, significantly reduced their risk of ulcer development. Pharmacokinetic and pharmacodynamic studies suggested that esomeprazole did not affect the pharmacokinetic parameters or the antiplatelet effects of aspirin. Therefore, for those patients who are at a high risk of developing a gastrointestinal ulcer, the benefit of adding esomeprazole likely outweighs the risks of longer term proton pump inhibitor use, and the combination can be recommended. Administering the two agents separately may also be more economical. On the other hand, for those patients at lower risk of developing a gastrointestinal ulcer, both the additional risk

  1. Pirfenidone enhances the efficacy of combined radiation and sunitinib therapy

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Seo-Hyun; Nam, Jae-Kyung; Jang, Junho; Lee, Hae-June, E-mail: hjlee@kcch.re.kr; Lee, Yoon-Jin, E-mail: yjlee8@kcch.re.kr

    2015-06-26

    Radiotherapy is a widely used treatment for many tumors. Combination therapy using anti-angiogenic agents and radiation has shown promise; however, these combined therapies are reported to have many limitations in clinical trials. Here, we show that radiation transformed tumor endothelial cells (ECs) to fibroblasts, resulting in reduced vascular endothelial growth factor (VEGF) response and increased Snail1, Twist1, Type I collagen, and transforming growth factor (TGF)-β release. Irradiation of radioresistant Lewis lung carcinoma (LLC) tumors greater than 250 mm{sup 3} increased collagen levels, particularly in large tumor vessels. Furthermore, concomitant sunitinib therapy did not show a significant difference in tumor inhibition versus radiation alone. Thus, we evaluated multimodal therapy that combined pirfenidone, an inhibitor of TGF-induced collagen production, with radiation and sunitinib treatment. This trimodal therapy significantly reduced tumor growth, as compared to radiation alone. Immunohistochemical analysis revealed that radiation-induced collagen deposition and tumor microvessel density were significantly reduced with trimodal therapy, as compared to radiation alone. These data suggest that combined therapy using pirfenidone may modulate the radiation-altered tumor microenvironment, thereby enhancing the efficacy of radiation therapy and concurrent chemotherapy. - Highlights: • Radiation changes tumor endothelial cells to fibroblasts. • Radio-resistant tumors contain collagen deposits, especially in tumor vessels. • Pirfenidone enhances the efficacy of combined radiation and sunitinib therapy. • Pirfenidone reduces radiation-induced collagen deposits in tumors.

  2. Combining Oncolytic Virotherapy with p53 Tumor Suppressor Gene Therapy

    Directory of Open Access Journals (Sweden)

    Christian Bressy

    2017-06-01

    Full Text Available Oncolytic virus (OV therapy utilizes replication-competent viruses to kill cancer cells, leaving non-malignant cells unharmed. With the first U.S. Food and Drug Administration-approved OV, dozens of clinical trials ongoing, and an abundance of translational research in the field, OV therapy is poised to be one of the leading treatments for cancer. A number of recombinant OVs expressing a transgene for p53 (TP53 or another p53 family member (TP63 or TP73 were engineered with the goal of generating more potent OVs that function synergistically with host immunity and/or other therapies to reduce or eliminate tumor burden. Such transgenes have proven effective at improving OV therapies, and basic research has shown mechanisms of p53-mediated enhancement of OV therapy, provided optimized p53 transgenes, explored drug-OV combinational treatments, and challenged canonical roles for p53 in virus-host interactions and tumor suppression. This review summarizes studies combining p53 gene therapy with replication-competent OV therapy, reviews preclinical and clinical studies with replication-deficient gene therapy vectors expressing p53 transgene, examines how wild-type p53 and p53 modifications affect OV replication and anti-tumor effects of OV therapy, and explores future directions for rational design of OV therapy combined with p53 gene therapy.

  3. Combining Oncolytic Virotherapy with p53 Tumor Suppressor Gene Therapy.

    Science.gov (United States)

    Bressy, Christian; Hastie, Eric; Grdzelishvili, Valery Z

    2017-06-16

    Oncolytic virus (OV) therapy utilizes replication-competent viruses to kill cancer cells, leaving non-malignant cells unharmed. With the first U.S. Food and Drug Administration-approved OV, dozens of clinical trials ongoing, and an abundance of translational research in the field, OV therapy is poised to be one of the leading treatments for cancer. A number of recombinant OVs expressing a transgene for p53 (TP53) or another p53 family member (TP63 or TP73) were engineered with the goal of generating more potent OVs that function synergistically with host immunity and/or other therapies to reduce or eliminate tumor burden. Such transgenes have proven effective at improving OV therapies, and basic research has shown mechanisms of p53-mediated enhancement of OV therapy, provided optimized p53 transgenes, explored drug-OV combinational treatments, and challenged canonical roles for p53 in virus-host interactions and tumor suppression. This review summarizes studies combining p53 gene therapy with replication-competent OV therapy, reviews preclinical and clinical studies with replication-deficient gene therapy vectors expressing p53 transgene, examines how wild-type p53 and p53 modifications affect OV replication and anti-tumor effects of OV therapy, and explores future directions for rational design of OV therapy combined with p53 gene therapy.

  4. Hadron cancer therapy complex employing non-scaling FFAG accelerator and fixed field gantry design

    CERN Document Server

    Keil, Eberhard; Trbojevic, D

    2007-01-01

    Non-scaling FFAG rings for cancer hadron therapy offer reduced physical aperture and large dynamic aperture as compared with scaling FFAGs. The variation of tune with energy implies the crossing of resonances during acceleration. Our design avoids intrinsic resonances, although imperfection resonances must be, and can be, crossed. We consider a system of three non-scaling FFAG rings for cancer therapy with 250 MeV protons and 400 MeV/u carbon ions. Hadrons are accelerated in a common RFQ and linear accelerator, and injected into the FFAG rings at .. .. . H+/C6+ ions are accelerated in the two smaller/larger rings to 31 and 250 MeV/68.8 and 400 MeV/u kinetic energy, respectively. The lattices consist of doublet cells with a straight section for RF cavities. The gantry with triplet cells accepts the whole required momentum range at fixed field. This unique design uses either high temperature super-conductors or super-conducting magnets reducing gantry size and weight. Elements with variable field at beginning a...

  5. 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

    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,

  6. Effects of a fixed combination of perindopril and indapamide in patients with type 2 diabetes and chronic kidney disease

    NARCIS (Netherlands)

    Lambers Heerspink, Hiddo J.; Ninomiya, Toshiharu; Perkovic, Vlado; Woodward, Mark; Zoungas, Sophia; Cass, Alan; Cooper, Mark; Grobbee, Diederick E.; Mancia, Giuseppe; Mogensen, Carl Eric; Neal, Bruce; Chalmers, John

    2010-01-01

    Individuals with diabetes and chronic kidney disease (CKD) are at high risk for cardiovascular disease. In these analyses of the ADVANCE trial, we assessed the effects of a fixed combination of perindopril-indapamide on renal and cardiovascular outcomes in patients with type 2 diabetes according to

  7. Bioequivalence of vildagliptin/metformin fixed-dose combination tablets and a free combination of vildagliptin and metformin in healthy subjects.

    Science.gov (United States)

    He, Y-L; Paladini, S; Sabia, H; Campestrini, J; Zhang, Y; Leon, S; Ligueros-Saylan, M; Jarugula, V

    2008-05-01

    To assess the bioequivalence of vildagliptin/metformin fixed-dose combination tablets (at doses of 50/500, 50/850 and 50/1,000 mg) with free combination of the individual drugs in healthy subjects. The pharmacokinetics of vildagliptin and metformin following administration of a fixed-dose combination tablet of vildagliptin/metformin at doses of 50/500 mg (Study I), 50/850 mg (Study II) and 50/1,000 mg (Study III) compared with administration of the individual drugs as free combinations were investigated. All three studies were open-label, single-center, randomized, two-period, two-treatment crossover studies in healthy subjects. Pharmacokinetic parameters (AUC(0-infinity), C(max), t(max), t(1/2) and CL/F) for vildagliptin and metformin across the three studies were similar whether vildagliptin and metformin were administered as a single fixed-dose combination tablet (vildagliptin/metformin 50/500, 50/850 or 50/1,000 mg) or as the respective individual tablets. The point estimates and 90% CI of the geometric mean ratios for vildagliptin and metformin C(max), AUC(0-t), and AUC(0-infinity) were all within the predefined bioequivalence range of 0.80 - 1.25. Administration of the vildagliptin/metformin combination tablets was well tolerated; the incidence of adverse events was similar to that observed with the respective free combinations of vildagliptin and metformin, and the most common individual adverse events were mild gastrointestinal events, which are commonly observed with metformin treatment. The fixed-dose combination tablet of vildagliptin/metformin is bioequivalent to administration of the individual drugs as a free combination at dose levels of 50/500, 50/850 and 50/1,000 mg and is well tolerated. Consequently, the fixed-dose combination tablets are considered therapeutically equivalent and exchangeable to the free combination in clinical practice. Furthermore, the fixed-dose combination tablets are expected to enhance convenience and thereby improve

  8. Tuberculosis drug issues: prices, fixed-dose combination products and second-line drugs.

    Science.gov (United States)

    Laing, R O; McGoldrick, K M

    2000-12-01

    Access to tuberculosis drugs depends on multiple factors. Selection of a standard list of TB drugs to procure is the first step. This paper reviews the advantages and disadvantages of procuring and using fixed-dose combination (FDC) products for both the intensive and continuation phases of treatment. The major advantages are to prevent the emergence of resistance, to simplify logistic management and to reduce costs. The major disadvantage is the need for the manufacturers to assure the quality of these FDCs by bioavailability testing. The paper reports on the inclusion of second-line TB drugs in the 1999 WHO Essential Drug List (EDL). The need to ensure that these drugs are used within established DOTS-Plus programs is stressed. The price of TB drugs is determined by many factors, including producer prices, local taxes and duties as well as mark-ups and fees. TB drug prices for both the public and private sectors from industrialized and developing countries are reported. Price trends over time are also reported. The key findings of this study are that TB drug prices have generally declined in developing countries while they have increased in developed countries, both for the public and private sectors. Prices vary between countries, with the US paying as much as 95 times the price paid in a specific developing country. The prices of public sector first-line TB drugs vary little between countries, although differences do exist due to the procurement methods used. The price of tuberculin, a diagnostic agent, has increased dramatically in the US, with substantial inter-country variations in price. The paper suggests that further research is necessary to identify the reasons for the price disparities and changes over time, and suggests methods which can be used by National Tuberculosis Programme managers to ensure availability of quality assured TB drugs at low prices.

  9. Safety and efficacy of NEPA, an oral fixed combination of netupitant and palonosetron, in older patients.

    Science.gov (United States)

    Aapro, Matti; Jordan, Karin; Gralla, Richard J; Rizzi, Giada; Rossi, Giorgia; Palmas, Marco; Alyasova, Anna V; Lisyanskaya, Alla S; Bošnjak, Snežana M; Hesketh, Paul J

    2017-01-01

    Prevention of chemotherapy-induced nausea and vomiting is critical in older patients with cancer. NEPA is an oral fixed combination of netupitant 300mg, a new NK 1 receptor antagonist (RA), and palonosetron 0.5mg, a pharmacologically distinct 5-HT 3 RA. This retrospective analysis evaluated the efficacy and safety of NEPA in older patients. Patients aged ≥65 and ≥70years from one phase II and two phase III trials were considered. Chemotherapy-naive patients with malignant tumors were treated with anthracycline-cyclophosphamide (AC), non-AC-based moderately emetogenic chemotherapy (non-AC MEC), or highly emetogenic chemotherapy (HEC). Following single-dose NEPA, patients received oral dexamethasone on day 1 (AC and non-AC MEC) or days 1-4 (HEC). Efficacy was evaluated through complete response (CR) in cycle 1. Safety was evaluated by AEs and ECGs. Data were summarized by descriptive statistics. Overall, 214 patients were ≥65years and 80 were ≥70years. A higher CR was observed in older patients versus the total population; in the acute phase >90% of patients ≥65years experienced CR. Efficacy was maintained over multiple cycles of chemotherapy. No significant nausea rates were generally higher in the older patients versus total population. Similar rates of AEs in the first treatment cycle were reported for patients ≥65years, ≥70years, and total population (72.9% vs 67.5% vs 70.0%, respectively). No cardiac safety concerns were raised. NEPA is highly effective in older patients receiving MEC or HEC regimens. NEPA is also well tolerated, demonstrating suitability for use in older patients who may have comorbidities. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Efficacy of tiotropium–olodaterol fixed-dose combination in COPD

    Directory of Open Access Journals (Sweden)

    Derom E

    2016-12-01

    Full Text Available Eric Derom, Guy G Brusselle, Guy F Joos Department of Respiratory Medicine, Ghent University Hospital, Ghent, BelgiumAbstract: Tiotropium–olodaterol, formulated in the Respimat soft-mist inhaler, is an inhaled fixed-dose combination (FDC of a long-acting muscarinic antagonist (LAMA and a long-acting β2-agonist (LABA, commercialized under the name of Spiolto or Stiolto. The efficacy of tiotropium–olodaterol 5–5 µg once daily in adult patients with COPD was documented in eleven large, multicenter trials of up to 52 weeks duration. Tiotropium–olodaterol 5–5 µg not only improved spirometric values to a significantly greater extent than placebo but also resulted in statistically significant beneficial effects on dyspnea, markers of hyperinflation, use of rescue medication, health-related quality of life, and exercise endurance. Improvements exceeded the minimal clinically important difference (MCID for forced expiratory volume in 1 second (FEV1, dyspnea, and quality of life. Differences between tiotropium–olodaterol 5–5 µg and the respective monocomponents were statistically significant for FEV1, dyspnea, markers of hyperinflation, use of rescue medication, and health-related quality of life, but did not reach the MCID. However, dual bronchodilatation significantly increased the number of patients who exceeded the MCID for dyspnea and quality of life. Moreover, tiotropium–olodaterol 5–5 µg was significantly more effective than salmeterol–fluticasone (FDC twice daily at improving pulmonary function. Differences between tiotropium–olodaterol and other LAMA/LABA FDCs were not observed for FEV1 or other efficacy markers. Therefore, tiotropium–olodaterol is a valuable option in the treatment of COPD patients who remain symptomatic under monotherapy. Keywords: COPD, bronchodilatation, dyspnea, exacerbation, exercise tolerance, LABA, LAMA, spirometry

  11. Hyperbilirubinemia without Transaminitis during Combined Therapy with Daclatasvir and Asunaprevir

    Directory of Open Access Journals (Sweden)

    Hayato Baba

    2016-07-01

    Full Text Available Daclatasvir (DCV and asunaprevir (ASV are direct-acting antivirals (DAAs used in the treatment of chronic hepatitis C virus (HCV infection. Combined therapy with DCV and ASV shows high efficacy and safety even in patients with cirrhosis. We encountered a patient exhibiting severe hyperbilirubinemia during combined therapy, which is an unreported side effect of DCV and ASV. A 78-year-old woman with cirrhosis developed hyperbilirubinemia >10 mg/dl without transaminitis 3 weeks after starting combined therapy. We suspected DAAs-induced liver disorder and discontinued treatment, which resulted in the improvement of hyperbilirubinemia. Caution is required in the use of DAAs for patients with advanced cirrhosis.

  12. Pharmacokinetics and pharmacodynamics of an extrafine fixed pMDI combination of beclometasone dipropionate/formoterol fumarate in adolescent asthma

    National Research Council Canada - National Science Library

    Kuna, Piotr; Govoni, Mirco; Lucci, Germano; Scuri, Mario; Acerbi, Daniela; Stelmach, Iwona

    2015-01-01

    ... of drugs to be administered via pMDI with or without a VHC is still not fully elucidated. What this Study Adds In adolescents, the overall systemic exposure to the active ingredients of an extrafine fixed pMDI combination of BDP/FF with or without VHC was equivalent to that of a free licenced combination of pMDIs of established safety and efficacy p...

  13. Gene and Stem Cell Therapy: Alone or in Combination?

    Directory of Open Access Journals (Sweden)

    Mohammad A. Rafi

    2011-12-01

    Full Text Available Introduction: Both gene and stem cell therapies hold great promise in the treatment of many genetic diseases and are currently focus of interest for many investigators. While both approaches are offering great and valuable treatment options for devastating and life-threatening diseases, they hold much greater promise in combination. Methods: As there are multiple options in selecting gene transfer vehicles among the non-viral and viral vectors, there are also many options among the different transplantable cell types ranging from lineage-restricted progenitor cells to multipotent and pluripotent stem cells. Here, combination of the gene therapy and stem cell therapy is discussed. Results: Several successful gene and stem cell therapies have been reported both in animal and human trials. Combination of the gene therapy and stem cell therapy can be carried out sequentially where the cell transplantation and the in vivo gene therapy are accomplished one after the other; or, as it is more commonly practiced, they can be carried out as ex vivo gene therapy where the transplantable cells are genetically modified outside the body before being transplanted into the body. Conclusion: The combination of the stem-cell technology with gene therapy has the potential of providing both regenerative tissue and therapeutic material simultaneously; therefore, having the benefits of both technologies.

  14. Clinical effectiveness of brinzolamide 1%–brimonidine 0.2% fixed combination for primary open-angle glaucoma and ocular hypertension

    Directory of Open Access Journals (Sweden)

    Sharma S

    2015-11-01

    Full Text Available Sourabh Sharma,1 Sameer Trikha,1 Shamira A Perera,1 Tin Aung1,2 1Glaucoma Department, Singapore Eye Research Institute, Singapore National Eye Centre, 2Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore Abstract: The main first-line treatment strategy for glaucoma is to reduce intraocular pressure (IOP by topical ocular hypotensive medications, but many patients require multiple medications for adequate IOP control. Fixed-combination therapies provide several benefits, including simplified treatment regimens, theoretical improved treatment adherence, elimination of the potential for washout of the first drug by the second, and the reduction in ocular exposure to preservatives. β-Adrenoceptor antagonists (particularly 0.5% timolol are the most commonly used agents in combination with other classes of drugs as fixed-combination eyedrops, but they are contraindicated in many patients, owing to local allergy or systemic side effects. A fixed-combination preparation without a β-blocker is therefore warranted. This paper reviews the clinical effectiveness of brinzolamide 1% and brimonidine 0.2% fixed combination (BBFC for use in patients with primary open-angle glaucoma and ocular hypertension. We searched PubMed and the ClinicalTrials.gov registry, and identified three randomized controlled trials comparing BBFC vs its constituents (brimonidine vs brinzolamide, and one comparing BBFC with unfixed brimonidine and brinzolamide. All of the studies demonstrated mean diurnal IOP to be statistically significantly lower in the BBFC group compared with constituent groups and noninferior to that with the concomitant group using two separate bottles. The safety profile of BBFC was consistent with that of its individual components, the most common ocular adverse events being ocular hyperemia, visual disturbances, and ocular allergic reactions. Common systemic adverse effects included altered taste

  15. Routine delivery of artemisinin-based combination treatment at fixed health facilities reduces malaria prevalence in Tanzania: an observational study

    Directory of Open Access Journals (Sweden)

    Khatib Rashid A

    2012-04-01

    Full Text Available Abstract Background Artemisinin-based combination therapy (ACT has been promoted as a means to reduce malaria transmission due to their ability to kill both asexual blood stages of malaria parasites, which sustain infections over long periods and the immature derived sexual stages responsible for infecting mosquitoes and onward transmission. Early studies reported a temporal association between ACT introduction and reduced malaria transmission in a number of ecological settings. However, these reports have come from areas with low to moderate malaria transmission, been confounded by the presence of other interventions or environmental changes that may have reduced malaria transmission, and have not included a comparison group without ACT. This report presents results from the first large-scale observational study to assess the impact of case management with ACT on population-level measures of malaria endemicity in an area with intense transmission where the benefits of effective infection clearance might be compromised by frequent and repeated re-infection. Methods A pre-post observational study with a non-randomized comparison group was conducted at two sites in Tanzania. Both sites used sulphadoxine-pyrimethamine (SP monotherapy as a first-line anti-malarial from mid-2001 through 2002. In 2003, the ACT, artesunate (AS co-administered with SP (AS + SP, was introduced in all fixed health facilities in the intervention site, including both public and registered non-governmental facilities. Population-level prevalence of Plasmodium falciparum asexual parasitaemia and gametocytaemia were assessed using light microscopy from samples collected during representative household surveys in 2001, 2002, 2004, 2005 and 2006. Findings Among 37,309 observations included in the analysis, annual asexual parasitaemia prevalence in persons of all ages ranged from 11% to 28% and gametocytaemia prevalence ranged from Interpretation The introduction of ACT at

  16. Significance of initial blood pressure and comorbidity for the efficacy of a fixed combination of an angiotensin receptor blocker and hydrochlorothiazide in clinical practice

    Directory of Open Access Journals (Sweden)

    Roland E Schmieder

    2009-11-01

    Full Text Available Roland E Schmieder1, Markus Schwertfeger2, Peter Bramlage31Department of Nephrology and Hypertension, University Hospital of Erlangen; Germany; 2Sanofi-Aventis Deutschland GmbH, Berlin, Germany; 3Institute of Cardiovascular Pharmacology and Epidemiology, Mahlow, GermanyBackground: Two-thirds of all patients with arterial hypertension need drug combinations to achieve blood pressure (BP goals. Fixed combinations have high efficacy and result in high patient compliance. 300 mg irbesartan plus 25 mg hydrochlorothiazide (HCTZ has been investigated only in clinical trials but not in daily practice.Methods: A multicenter, noninterventional, noncontrolled observational study with 8123 patients seen by 1604 physicians in daily practice. BP reduction (office measurements, co-morbid disease and tolerability were documented over a 6-month observational period.Results: At mean baseline BP of 161 ± 15/94 ± 10 mmHg, administering of fixed combination resulted in a substantial BP reduction averaging 28 ± 15/14 ± 10 mmHg (P < 0.001. Decrease of systolic BP ran parallel with increasing systolic baseline BP (Spearman’s Rho –0.731; P < 0.0001; diastolic BP vs diastolic baseline BP Rho 0.740; P < 0.0001, independent from patient characteristics (age, obesity, diabetes or nephropathy but enhanced with short history of hypertension (P < 0.0001 vs long history, prior beta blockers (P = 0.001 vs prior angiotensin receptor blockers [ARBs], prior calcium channel blockers (P = 0.046 vs prior ARBs and no prior medication (P = 0.012 vs prior ARBs. High compliance (>98% and low incidence of adverse events (0.66% were documented.Conclusions: The fixed combination of 300 mg irbesartan with 25 mg HCTZ was efficacious and tolerable in an unselected patient population in primary care.Keywords: hypertension, combination therapy, obesity, irbesartan, noninterventional study, diuretics

  17. Esomeprazole and aspirin fixed combination for the prevention of cardiovascular events

    Directory of Open Access Journals (Sweden)

    Sylvester KW

    2013-05-01

    Full Text Available Katelyn W Sylvester,1 Judy WM Cheng,1,3 Mandeep R Mehra2,41Department of Pharmacy, 2Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA; 3Massachusetts College of Pharmacy and Health Sciences, Boston, MA, 4Harvard Medical School, Boston MA, USAAbstract: Low dose aspirin therapy plays a fundamental role in both the primary and secondary prevention of cardiovascular events. Although the evidence using low dose aspirin for secondary prevention is well-established, the decision to use aspirin for primary prevention is based on an evaluation of the patient’s risk of cardiovascular events compared to their risk of adverse events, such as bleeding. In addition to the risk of bleeding associated with long term aspirin administration, upper gastrointestinal side effects, such as dyspepsia often lead to discontinuation of therapy, which places patients at an increased risk for cardiovascular events. One option to mitigate adverse events and increase adherence is the addition of esomeprazole to the medication regimen. This review article provides an evaluation of the literature on the concomitant use of aspirin and esomeprazole available through February 2013. The efficacy, safety, tolerability, cost effectiveness, and patient quality of life of this regimen is discussed. A summary of the pharmacokinetic and pharmacodynamic interactions between aspirin and esomeprazole, as well as other commonly used cardiovascular medications are also reviewed. The addition of esomeprazole to low dose aspirin therapy in patients at high risk of developing gastric ulcers for the prevention of cardiovascular disease, significantly reduced their risk of ulcer development. Pharmacokinetic and pharmacodynamic studies suggested that esomeprazole did not affect the pharmacokinetic parameters or the antiplatelet effects of aspirin. Therefore, for those patients who are at a high risk of developing a gastrointestinal ulcer, the benefit of adding esomeprazole

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

    Directory of Open Access Journals (Sweden)

    Santiago Moreno Guillen

    2017-09-01

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

  19. Naphthoquine: An Emerging Candidate for Artemisinin Combination Therapy.

    Science.gov (United States)

    Moore, Brioni R; Laman, Moses; Salman, Sam; Batty, Kevin T; Page-Sharp, Madhu; Hombhanje, Francis; Manning, Laurens; Davis, Timothy M E

    2016-05-01

    Naphthoquine is a 4-aminoquinoline antimalarial drug first synthesised in China in 1986 but which was not developed for clinical use until the late 1990s. Early in vitro parasite sensitivity and in vivo efficacy data, together with a long terminal elimination half-life (up to 23 days), suggested that it could be used as monotherapy for uncomplicated falciparum and vivax malaria, but is now marketed as a single-dose, fixed co-formulation with artemisinin in a milligram per kilogram ratio of 1:2.5. This form of artemisinin combination therapy (ACT) has also shown high cure rates, especially in two randomised trials in which, consistent with World Health Organization recommendations for all ACTs, it was administered daily for 3 days rather than as single dose for Plasmodium falciparum and P. vivax infections (28-day adequate clinical and parasitological response ≥98.4 %). Although detailed safety monitoring has been performed in a minority of subjects, >4000 healthy volunteers and patients with malaria have been exposed to naphthoquine without any documented significant toxicity. As with other 4-aminoquinolines, naphthoquine is associated with prolongation of the electrocardiographic QT interval but not with cardiac or neurological events. It has been administered to children as young as 4 months of age but, due to a lack of pharmacokinetic, efficacy and toxicity data in young infants and in pregnant/lactating women, it should not be used in these vulnerable patient groups.With the emergence of parasite resistance to other ACTs, naphthoquine partnered with a potent artemisinin derivative may prove a viable alternative treatment for uncomplicated malaria.

  20. Dentoskeletal changes induced by the Jasper jumper and the activator-headgear combination appliances followed by fixed orthodontic treatment.

    Science.gov (United States)

    Lima, Karina Jerônimo Rodrigues Santiago de; Henriques, José Fernando Castanha; Janson, Guilherme; Pereira, Suelen Cristina da Costa; Neves, Leniana Santos; Cançado, Rodrigo Hermont

    2013-05-01

    The aim of this study was to compare the dentoskeletal changes of patients with Class II Division 1 malocclusion treated with either the Jasper jumper appliance or the activator-headgear combination, both associated with fixed appliances. The sample comprised 72 subjects with Class II Division 1 malocclusion divided into 3 groups: group 1 included 25 subjects treated with fixed appliances and the force modules of the Jasper jumper at an initial mean age of 12.72 years, group 2 included 25 subjects treated with the activator-headgear combination followed by fixed appliances at an initial mean age of 11.07 years, and group 3 included 22 untreated subjects at an initial mean age of 12.67 years. Initial cephalometric characteristics and dentoskeletal changes were compared with analysis of variance. Both experimental groups had similar dentoskeletal changes: restrictive effect on the maxilla, clockwise mandibular rotation and a slight increase in anterior face height, retrusion of the maxillary incisors, distalization of the maxillary molars, protrusion of the mandibular incisors, extrusion of the mandibular molars, and significant improvements of the maxillomandibular relationship, overjet, overbite, and the molar relationship. The effects of the Jasper jumper and the activator-headgear combination followed by fixed orthodontic appliances were similar in Class II malocclusion treatment. Copyright © 2013 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  1. Perception of the efficacy of artemisinin-based combination therapy ...

    African Journals Online (AJOL)

    West Nigeria and perception of artemisinin-based combination therapy (ACT). Design and methods-About 180 pre-tested questionnaires were administered to randomly selected nurses out of which 155 were sufficiently completed and ...

  2. NMR with Combined Antiangiogenic and Radiation Therapies - Breast Cancer

    National Research Council Canada - National Science Library

    Brown, Stephen

    2000-01-01

    The original goal of the present study was to determine optimal strategies for combining radiation and antiangiogenic therapies in spontaneous murine tumors and to evaluate the potential of Nuclear Magnetic Resonance (NMR...

  3. 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.

  4. Intraocular pressure-lowering effects of commonly used fixed-combination drugs with timolol: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Jin-Wei Cheng

    Full Text Available BACKGROUND: The first goal of medical therapy in glaucoma is to reduce intraocular pressure (IOP, and the fixed-combination medications are needed to achieve sufficiently low target IOP. The aim of this systematic review and meta-analysis is to evaluate IOP-lowering effect of the commonly used fixed-combination drugs containing 0.5% timolol. METHODS: Pertinent publications were identified through systematic searches. Over 85% of the patients had to be diagnosed with primary open-angle glaucoma (POAG or ocular hypertension (OHT. Forty-one randomized clinical trials were included in the meta-analysis. The main efficacy measures were the absolute and relative values of mean diurnal IOP reduction, and the highest and lowest IOP reductions on the diurnal IOP curve. The pooled 1- to 3-month IOP-lowering effects after a medicine-free washout period was calculated by performing meta-analysis using the random effects model, and relative treatment effects among different fixed combinations were assessed using a mixed-effects meta-regression model. RESULTS: The relative reductions for mean diurnal IOP were 34.9% for travoprost/timolol, 34.3% for bimatoprost/timolol, 33.9% for latanoprost/timolol, 32.7% for brinzolamide/timolol, 29.9% for dorzolamide/timolol, and 28.1% for brimonidine/timolol. For the highest IOP decrease, relative reductions ranged from 31.3% for dorzolamide/timolol to 35.5% for travoprost/timolol; for the lowest IOP decrease, those varied from 25.9% for dorzolamide/timolol to 33.1% for bimatoprost/timolol. Both latanoprost/timolol and travoprost/timolol were more effective in lowering mean diurnal IOP than brimonidine/timolol (WMD: 5.9 and 7.0 and dorzolamide/timolol (WMD: 3.8 and 3.3. CONCLUSIONS: All six commonly used fixed-combination drugs containing timolol can effectively lower IOP in patients with POAG and OHT, and both latanoprost/timolol and travoprost/timolol might achieve better IOP-lowering effects among the six fixed-combination

  5. Assessment of ocular hypotensive effect and safety 12 months after changing from an unfixed combination to a latanoprost 0.005% + timolol maleate 0.5% fixed combination

    Directory of Open Access Journals (Sweden)

    Inoue K

    2012-04-01

    Full Text Available Kenji Inoue1, Ryoko Okayama1, Risako Higa1, Masato Wakakura1, Goji Tomita21Inouye Eye Hospital, 4-3 Kanda-Surugadai, Chiyoda-ku, 2Second Department of Ophthalmology, Toho University School of Medicine, Meguro-ku, Tokyo, JapanBackground: Latanoprost 0.005% + timolol maleate 0.5% combined eyedrops were recently made available in Japan. We prospectively investigated the intraocular pressure (IOP-lowering effect, visual preservation effect, and adverse reactions of a one-year administration of this fixed combination.Methods: The subjects included 162 eyes from 162 patients diagnosed with either primary open-angle glaucoma or ocular hypertension and using an unfixed combination of latanoprost 0.005% and timolol maleate 0.5%. The unfixed combination was discontinued and replaced with the latanoprost 0.005% + timolol maleate 0.5% fixed combination with no washout period. IOP was measured before (baseline and 3, 6, 9, and 12 months after the change. The mean deviation value of Humphrey field analysis was compared. Adverse reactions were examined at every follow-up.Results: No significant differences were found between mean IOP values obtained at baseline (mean ± standard deviation, 15.2 ± 3.3 mmHg 3 months (15.1 ± 3.2 mmHg, 6 months (15.3 ± 3.1 mmHg, 9 months (15.3 ± 3.1 mmHg, and 12 months (15.1 ± 3.2 mmHg after the change from the unfixed to the fixed combination of eyedrops (P = 0.212. In addition, no significant differences were observed between mean deviation values obtained at baseline (–9.11 ± 6.94 dB and 12 months (–10.08 ± 7.24 dB after the change (P = 0.114. Thirty-one patients discontinued the fixed combination within 12 months of replacement, due to an insufficient IOP decrease (20 patients, 12.3% and adverse reactions (11 patients, 6.8%.Conclusion: Following replacement of two eyedrop medications (latanoprost 0.005% and timolol maleate 0.5% by one fixed combination (latanoprost 0.005% + timolol maleate 0.5%, IOP and visual field

  6. Pharmacokinetics and Bioavailability of a Fixed-Dose Combination of Ibuprofen and Paracetamol after Intravenous and Oral Administration.

    Science.gov (United States)

    Atkinson, Hartley C; Stanescu, Ioana; Frampton, Chris; Salem, Isam I; Beasley, Charles P H; Robson, Richard

    2015-10-01

    Previously published studies have suggested the lack of a pharmacokinetic interaction between ibuprofen and paracetamol when they are delivered as a fixed-dose oral combination. The aim of this study was to determine the pharmacokinetic profile and safety of a fixed-dose intravenous (IV) combination, containing 3 mg/mL ibuprofen and 10 mg/mL paracetamol, in comparison with its individual components. The study also assessed the relative bioavailability of the same doses of the active ingredients when they were administered as an oral formulation. A single-dose, open-label, randomized, five-period cross-over sequence pharmacokinetic study was undertaken in 30 healthy volunteers. Serial plasma samples were assayed for both paracetamol and ibuprofen concentrations, using validated liquid chromatography-tandem mass spectrometry methods. Pharmacokinetic parameters were computed using standard non-compartmental analyses. Adverse events were also assessed. The ratios of the maximum measured plasma concentration (C max), the area under the plasma concentration-time curve (AUC) from time zero to the time of the last measurable plasma concentration (AUCt ) and AUC from time zero to infinity (AUC∞) were analysed for bioequivalence as determined by 90% confidence intervals. The pharmacokinetic parameters of ibuprofen and paracetamol were very similar for the combination and monotherapy IV preparations; the ratios of the C max, AUC t and AUC∞ values fell within the 80-125% acceptable bioequivalence range. Precise dose proportionality for both compounds was also determined for the half dose of the IV formulation in comparison with the full dose. The relative bioavailability of paracetamol (93.78%) and ibuprofen (96.45%) confirmed the pharmacokinetic equivalence of the oral and IV formulations of the fixed-dose combination. Concomitant administration of 3 mg/mL ibuprofen and 10 mg/mL paracetamol in a fixed-dose IV combination does not alter the pharmacokinetic profiles of

  7. Early orthopedic correction of skeletal Class III malocclusion using combined reverse twin block and face mask therapy

    Directory of Open Access Journals (Sweden)

    Vinay Kumar Chugh

    2015-01-01

    Full Text Available A 6-year 8-month-old girl presented with a moderate Class III malocclusion characterized by mid-face deficiency and an anterior cross bite. In the first phase, the patient was treated with combination of reverse twin block and facemask therapy. In phase two, fixed appliances were placed in the permanent dentition. The post treatment results were good and a favorable growth tendency could be observed. The correction of the Class III malocclusion occurred by a combination of skeletal and dental improvements. This report shows successful correction of skeletal Class III malocclusion in the early transitional dentition using combination therapy.

  8. Early orthopedic correction of skeletal Class III malocclusion using combined reverse twin block and face mask therapy.

    Science.gov (United States)

    Chugh, Vinay Kumar; Tandon, Pradeep; Prasad, Veerendra; Chugh, Ankita

    2015-01-01

    A 6-year 8-month-old girl presented with a moderate Class III malocclusion characterized by mid-face deficiency and an anterior cross bite. In the first phase, the patient was treated with combination of reverse twin block and facemask therapy. In phase two, fixed appliances were placed in the permanent dentition. The post treatment results were good and a favorable growth tendency could be observed. The correction of the Class III malocclusion occurred by a combination of skeletal and dental improvements. This report shows successful correction of skeletal Class III malocclusion in the early transitional dentition using combination therapy.

  9. The comparison between monotherapy and combination therapy in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Khalvat A

    2007-05-01

    Full Text Available Background: Rheumatoid arthritis (RA is a chronic inflammatory condition. The condition can affected many tissues throught out the body, but the joints are usually most severely affected. The high incidence of RA, the conventional treatments and the experimental observation have shown by combination therapy, the disease symptoms of the patients reduce. To compare the efficacy and tolerability of single-agent Hydroxychloroquin (HCQ with combination therapies composed of (HCQ and Methotrexate (MTX and (HCQ, (MTX and Sulfasalazin (SSZ in active rheumatoid arthritis patients with additive arthritis. Methods: One hundred and twenty RA patients with active arthritis (male/female: 30/90 who were treated in rheumatology clinic between 2003 and 2005 were enrolled in this trial. Patients treated with (HCQ alone(200 mg/daywere include in group (I, patients treated with combination of (HCQ (200 mg/dayand (MTX (7.5mg/weekin group (II,and patents treated with combination of (HCQ (200mg/day,(MTX (7.5mg/weekand (SSZ(1 gr/dayin group (III, Forty patients (male/female:10/30 in group (I,(II and (IIIwere eligible for statistical analysis at the end of study. Changes in variable were compared by the T-test. Results: The combination of (MTX, (HCQand (SSZ and the combination of (MTX and (HCQ were more effective regarding the clinical and laboratory parameters than (HCQ alone (P<0.05. Moreover the combination of (MTX, (HCQ and (SSZ was more effective than the combination of (MTX and (HCQ (P<0.05. Combination therapies seem to be more effective and no more toxic than monotherapy in RA patients with additive arthritis. Conclusion: Combination therapy with methotrexate, hydroxychloroquin and sulfasalazin is more effective than hydroxychloroquin alone or a combination of methotrexate and hydroxychloroquin in RA. We suggest starting combination therapy for the patients with early RA, when the diagnosis has been established.

  10. Safety assessment of combination therapies in the treatment of obesity: focus on naltrexone/bupropion extended release and phentermine-topiramate extended release.

    Science.gov (United States)

    Halpern, Bruno; Mancini, Marcio C

    2017-01-01

    Few studies on combination therapies for the treatment of obesity had been conducted until recently, when two fixed-dose combinations, bupropion-naltrexone ER fixed-dose combination and phentermine-topiramate ER titrated-dose combinations were evaluated in clinical studies that ultimately led to FDA approval. Areas covered: In this review, we discuss safety concerns about both combinations, the rationale and history of combination therapies for obesity (including phentermine plus fenfluramine), and possible future new combinations. Expert opinion: Combination therapies are a promising new area in obesity treatment, similar to what occurs with diabetes and hypertension. Safety assessment is highly important due to the high number of potential users on a chronic basis.

  11. Efficacy of rifampicin combination therapy on selected non ...

    African Journals Online (AJOL)

    Combination therapy or polytherapy is the use of more than one antibacterial agent in the treatment of a single infection. In this study, rifampicin that was mainly used in the treatment of mycobacterial infections has been used in combination with other agents in non mycobacterial organisms. Clinical isolates of ...

  12. Antihypertensive combination therapy in primary care offices: results of a cross-sectional survey in Switzerland

    Directory of Open Access Journals (Sweden)

    Roas S

    2014-12-01

    Full Text Available Susanne Roas,1 Felix Bernhart,2 Michael Schwarz,3 Walter Kaiser,4 Georg Noll5 1Department of Internal Medicine, University Hospital, Zurich, 2Private Practice, Biberist, 3Ambulatorium Wiesendamm, Basel, 4Healthworld (Schweiz AG, Steinhausen, 5HerzKlinik Hirslanden, Zurich, Switzerland Background: Most hypertensive patients need more than one substance to reach their target blood pressure (BP. Several clinical studies indicate the high efficacy of antihypertensive combinations, and recent guidelines recommend them in some situations even as initial therapies. In general practice they seem widespread, but only limited data are available on their effectiveness under the conditions of everyday life. The objectives of this survey among Swiss primary care physicians treating hypertensive patients were: to know the frequency of application of different treatment modalities (monotherapies, free individual combinations, single-pill combinations; to see whether there are relationships between prescribed treatment modalities and patient characteristics, especially age, treatment duration, and comorbidities; and to determine the response rate (percentage of patients reaching target BP of different treatment modalities under the conditions of daily practice. Methods: This cross-sectional, observational survey among 228 randomly chosen Swiss primary care physicians analyzed data for 3,888 consecutive hypertensive patients collected at one single consultation. Results: In this survey, 31.9% of patients received monotherapy, 41.2% two substances, 20.9% three substances, and 4.7% more than three substances. By combination mode, 34.9% took free individual combinations and 30.0% took fixed-dose single-pill combinations. Combinations were more frequently given to older patients with a long history of hypertension and/or comorbidities. In total, 67.8% of patients achieved their BP target according to their physician's judgment. When compared, single

  13. Combination therapy: the next opportunity and challenge of medicine

    Directory of Open Access Journals (Sweden)

    Marincola Francesco M

    2011-07-01

    Full Text Available Abstract From an historical point of view, combination therapy was the basis for the care of important diseases like infection diseases or cancer. Today the "cocktail drug" of the Highly Active Anti Retroviral Therapy (HAART has reduced the death for HIV infection changing the outcome of such disease. Moreover, the combination of different strategies changed the course of transplants (both in haematology and surgical transplant. Different diseases with high social impact including cardiovascular, metabolic (obesity, hypercholesterolaemia and diabetes and autoimmune diseases, have better results with combinations of different drug classes of drugs. After recent successes in the immunotherapy field (Sepuleucel-T, ipilimumab and the new promising small molecule therapies, cancer should be the next challenge for combination strategies.

  14. About Fixed Points in CAT(0 Spaces under a Combined Structure of Two Self-Mappings

    Directory of Open Access Journals (Sweden)

    Manuel De la Sen

    2017-01-01

    Full Text Available This paper investigates some fixed point-related questions including the sequence boundedness and convergence properties of mappings QtSx,Ty=tSx⊕1-tTy defined in CAT0 spaces, which are parameterized by a scalar t∈0,1, where S,T:  X→X are nonexpansive Lipschitz-continuous mappings and X,d is a metric space which is a CAT0 space.

  15. Development and evaluation of fixed dose bi therapy sublingual tablets for treatment stress hypertension and anxiety

    Directory of Open Access Journals (Sweden)

    Mohamed A El-Nabarawi

    2013-01-01

    Full Text Available Objective: A stress induced rise in the blood pressure. Some believe that patients with hypertension are characterized by a generalized state of increased anxiety. Aim: The purpose of this study is to prepare a fixed dose bi therapy using bisoprolol hemifumarate (BH as antihypertensive drug and buspirone hydrochloride (BuHCl as anxiolytic drug, which can be used to treat both diseases concomitantly. Using sublingual tablets is hopeful to improve the BuHCl poor oral bioavailability and to facilitate administration to patients experiencing problems with swallowing. Materials and Methods: A total of 5mg BH and 10mg BuHCl were selected based on compatibility study. A 3×22 full factorial design was adopted for the optimization of the tablets prepared by direct compression method. The effects of the filler type, the binder molecular weight, and the binder type were studied. The prepared formulae were evaluated according to their physical characters as hardness, friability, disintegration time (new modified method and in vivo disintegration time and wetting properties. In vitro drugs dissolute, permeation through the buccal mucosa and the effect of storage were analyzed by a new valid high pressure liquid chromatography (HPLC method. Bioavailability study of the selected formula study was carried out and followed by the clinical. Results: The optimized tablet formulation showed accepted average weight, hardness, wetting time, friability, content uniformity, disintegration time (less than 3 min. Maximum drug release could be achieved with in 10 min. In addition enhancing drug permeation through the buccal mucosa and, the maximum concentration of the drug that reached the blood was in the first 10 min which means a rapid onset of action and improved the extent of both drug′s absorption. Conclusion: The results revealed that sublingual (F6 tablets containing both drugs would maintain rapid onset of action, and increase bioavailability. BuHCl with BH

  16. Transcriptional changes induced by bevacizumab combination therapy in responding and non-responding recurrent glioblastoma patients

    DEFF Research Database (Denmark)

    Urup, Thomas; Staunstrup, Line Maersk; Michaelsen, Signe Regner

    2017-01-01

    and resistance to bevacizumab combination therapy.Methods: Recurrent glioblastoma patients who had biomarker-accessible tumor tissue surgically removed both before bevacizumab treatment and at time of progression were included. Patients were grouped into responders (n = 7) and non-responders (n = 14). Gene...... expression profiling of formalin-fixed paraffin-embedded tumor tissue was performed using RNA-sequencing.Results: By comparing pretreatment samples of responders with those of non-responders no significant difference was observed. In a paired comparison analysis of pre- and posttreatment samples of non...

  17. Combining GPS + GLONASS observations to improve the fixing percentage and precision of long baselines with limited data

    Science.gov (United States)

    Liu, Yanyan; Ye, Shirong; Jiang, Peng; Song, Weiwei; Lou, Yidong

    2016-03-01

    Although commercial GPS + GLONASS real-time kinematic systems are available for more than 15 years, GLONASS ambiguity resolution is limited to short baselines within a few tens of kilometers. Furthermore, until now, none of the IGS analysis center has reported ambiguity resolution for GLONASS long baselines in their routine GNSS data processing. The currently published double- or single-differencing techniques are all concentrated on short baselines and are not applicable for long baselines. In this study, we propose a new Single Differencing Between-Receiver (SDBR) method, which is especially suitable for GPS + GLONASS long baseline ambiguity resolution. The SDBR wide-lane ambiguity is directly fixed by rounding with SDBR Hatch-Melbourne-Wübbena combination; the SDBR narrow-lane ambiguity is directly fixed with LAMBDA method. To eliminate the receiver Inter Frequency Bias (IFB), we selected 63 stations with identical IFBs, so that IFBs can be eliminated by SDBR. The results shows, adding GLONASS can improve the fixing rate from 87.8% to 98.8% for half-hourly static solutions, and from 99.3% to 99.9% for hourly static solutions. The position accuracy is also improved significantly for each strategy respectively. Kinematic solutions with different session length are also performed and the fixing rate is improved even more significantly than static solutions.

  18. Gastrointestinal Toxicities With Combined Antiangiogenic and Stereotactic Body Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Pollom, Erqi L.; Deng, Lei [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Pai, Reetesh K. [Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (United States); Brown, J. Martin; Giaccia, Amato; Loo, Billy W.; Shultz, David B.; Le, Quynh Thu; Koong, Albert C. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Chang, Daniel T., E-mail: dtchang@stanford.edu [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States)

    2015-07-01

    Combining the latest targeted biologic agents with the most advanced radiation technologies has been an exciting development in the treatment of cancer patients. Stereotactic body radiation therapy (SBRT) is an ablative radiation approach that has become established for the treatment of a variety of malignancies, and it has been increasingly used in combination with biologic agents, including those targeting angiogenesis-specific pathways. Multiple reports have emerged describing unanticipated toxicities arising from the combination of SBRT and angiogenesis-targeting agents, particularly of late luminal gastrointestinal toxicities. In this review, we summarize the literature describing these toxicities, explore the biological mechanism of action of toxicity with the combined use of antiangiogenic therapies, and discuss areas of future research, so that this combination of treatment modalities can continue to be used in broader clinical contexts.

  19. [EFFECTIVENESS OF FIXED COMBINATION OF PERINDOPRILARGININE AND AMLODIPINE FOR THE TREATMENT OF ARTERIAL HYPERTENSION WITH CONCOMITANT CHRONIC CARDIAC INSUFFICIENCY AND SIGNS OF CHRONIC KIDNEY DISEASE].

    Science.gov (United States)

    Kuznetsova, T E; Borovkova, N Yu

    2015-01-01

    to study effectiveness of a fixed combination of perindopril arginine and amlodipine besylate for the treatment of arterial hypertension with concomitant chronic cardiac insufficiency and signs of chronic kidney disease Materials and methods: 53 (44.9%) patients aged 64.5±8.2 yr with signs of chronic kidney disease (CKD) were selected from 118 subjects with grade II-III essential AH and chronic cardiac insufficiency They had an increased blood cystatin C level (mean 1.4±0.3 mg/l) and/or decreased glomerular filtration rate (GFR) calculated by 3 formulas: 77.6±15.9 (MDRD), 79.3±17.1 (CKD-EPI) and 57.7±15.2 ml/min/1. 73 m3 (from cystatin C level). Fixed combinations of perindopril arginine and amlodipine besylate (5/5, 5/10, 10/10 mg) were used to treat the patients. Their effectiveness was evaluated 2 months after the onset of therapy based on results of AP measurement, 24 hr AP monitoring, assessment of clinical conditions and 6 min walk test. Blood creatinine, urea and cystatin C levels and GFR were measured. Target AP was achieved in 82.6% of the patients. Systolic AP (SAP) decreased significantly from 172±11.2 to 135.7±8.2 mmHg (pinsufficiency having signs of chronic kidney disease.

  20. Treating Hypothyroidism with Thyroxine/Triiodothyronine Combination Therapy in Denmark

    DEFF Research Database (Denmark)

    Michaelsson, Luba Freja; Medici, Bjarke Borregaard; la Cour, Jeppe Lerche

    2015-01-01

    BACKGROUND: Five to ten percent of patients with hypothyroidism describe persistent symptoms despite being biochemically well regulated on levothyroxine (L-T4). Thyroxine (T4)/triiodothyronine (T3) combination therapy [L-T4/liothyronine (L-T3) or desiccated thyroid] are still regarded as experime......BACKGROUND: Five to ten percent of patients with hypothyroidism describe persistent symptoms despite being biochemically well regulated on levothyroxine (L-T4). Thyroxine (T4)/triiodothyronine (T3) combination therapy [L-T4/liothyronine (L-T3) or desiccated thyroid] are still regarded...... after a patient published a book describing her experiences with hypothyroidism and treatment. OBJECTIVE: To investigate current Danish trends in the use of T4/T3 combination therapy. METHODS: We used an Internet-based questionnaire, distributed as a link via two Danish patient fora. Further...

  1. Combining initial-state resummation with fixed-order calculations of electroweak corrections arXiv

    CERN Document Server

    Bauer, Christian W.; Webber, Bryan R.

    We present a resummation of those double-logarithmically enhanced electroweak correction that arise in pp colliders because protons are not SU(2) singlets, by solving DGLAP equations in the full Standard Model. We then show how to match these results with those of fixed-order electroweak calculations. At a 100 TeV pp collider, contributions beyond order alpha are ~ 10% at partonic center-of-mass energies of a few TeV. These are mainly due to initial states with massive vector bosons.

  2. Efficacy and safety of a switch to latanoprost 0.005% + timolol maleate 0.5% fixed combination eyedrops from latanoprost 0.005% monotherapy

    Directory of Open Access Journals (Sweden)

    Inoue K

    2012-05-01

    Full Text Available Kenji Inoue,1 Takayuki Fujimoto,1 Risako Higa,1 Ryo Moriyama,1 Hiromi Kohmoto,1 Haruka Nagumo,1 Masato Wakakura,1 Goji Tomita21Inouye Eye Hospital, Chiyoda-ku, Tokyo, 2Second Department of Ophthalmology, Toho University School of Medicine, Meguro-ku, Tokyo, JapanBackground: The purpose of this prospective study was to investigate the intraocular pressure (IOP-lowering effect and safety of latanoprost 0.005% + timolol maleate 0.5% fixed combination eyedrops, now available in Japan.Materials and methods: Thirty-one patients diagnosed with primary open-angle glaucoma who had an insufficient intraocular pressure (IOP decrease with latanoprost 0.005% eyedrop monotherapy were enrolled. The latanoprost 0.005% eyedrops were discontinued, and administration of latanoprost 0.005%/timolol maleate 0.5% fixed combination eyedrops was initiated without any washout period. IOP was compared before and at months 1, 3, and 6 after the switch. The incidence of adverse reactions was investigated at every follow-up visit.Results: Mean IOP was 17.3 ± 2.7 mmHg before the switch, 15.5 ± 2.6 mmHg one month after the switch, 14.9 ± 2.4 mmHg 3 months after the switch, and 15.1 ± 2.2 mmHg 6 months after the switch, indicating that IOP decreased significantly after the change. The IOP reduction rate was 9.9% ± 11.5% after one month, 13.1% ± 10.9% after 3 months, and 11.2% ± 11.8% after 6 months. Two patients (6.5% discontinued therapy due to adverse reactions (one case each of itchiness and bradycardia.Conclusion: When latanoprost 0.005% eyedrop monotherapy was replaced by latanoprost 0.005% + timolol maleate 0.5% fixed combination eyedrops, IOP decreased significantly without increasing the frequency of administration, and safety was satisfactory.Keywords: latanoprost 0.005%, timolol maleate 0.5%, fixed combination, eyedrops, intraocular pressure, switch

  3. Combination antitumor therapy with targeted dual-nanomedicines.

    Science.gov (United States)

    Dai, Wenbing; Wang, Xiaoyou; Song, Ge; Liu, Tongzhou; He, Bing; Zhang, Hua; Wang, Xueqing; Zhang, Qiang

    2017-06-01

    Combination therapy is one of the important treatment strategies for cancer at present. However, the outcome of current combination therapy based on the co-administration of conventional dosage forms is suboptimal, due to the short half-lives of chemodrugs, their deficient tumor selectivity and so forth. Nanotechnology-based targeted delivery systems show great promise in addressing the associated problems and providing superior therapeutic benefits. In this review, we focus on the combination of therapeutic strategies between different nanomedicines or drug-loaded nanocarriers, rather than the co-delivery of different drugs via a single nanocarrier. We introduce the general concept of various targeting strategies of nanomedicines, present the principles of combination antitumor therapy with dual-nanomedicines, analyze their advantages and limitations compared with co-delivery strategies, and overview the recent advances of combination therapy based on targeted nanomedicines. Finally, we reviewed the challenges and future perspectives regarding the selection of therapeutic agents, targeting efficiency and the gap between the preclinical and clinical outcome. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Tramadol/Paracetamol Fixed-Dose Combination for Chronic Pain Management in Family Practice: A Clinical Review

    Science.gov (United States)

    Morón Merchante, Ignacio; Pergolizzi, Joseph V.; van de Laar, Mart; Mellinghoff, Hans-Ulrich; O'Brien, Joanne; Perrot, Serge; Raffa, Robert B.

    2013-01-01

    The family practitioner plays an important role in the prevention, diagnosis, and early management of chronic pain. He/she is generally the first to be consulted, the one most familiar with the patients and their medical history, and is likely the first to be alerted in case of inadequate pain control or safety and tolerability issues. The family practitioner should therefore be at the center of the multidisciplinary team involved in a patient's pain management. The most frequent indications associated with chronic pain in family practice are of musculoskeletal origin, and the pain is often multimechanistic. Fixed-dose combination analgesics combine compounds with different mechanisms of action; their broader analgesic spectrum and potentially synergistic analgesic efficacy and improved benefit/risk ratio might thus be useful. A pain specialist meeting held in November 2010 agreed that the fixed-dose combination tramadol/paracetamol might be a useful pharmacological option for chronic pain management in family practice. The combination is effective in a variety of pain conditions with generally good tolerability. Particularly in elderly patients, it might be considered as an alternative to conventional analgesics such as NSAIDs, which should be used rarely with caution in this population. PMID:24959571

  5. Atypical and Typical Winter Depressive Symptoms and Responsiveness to Light Therapy, Cognitive-Behavioral Therapy, or Combination Treatment

    Science.gov (United States)

    2005-01-01

    Cognitive - Behavioral Therapy , or Combination Treatment” Name of Candidate: Leigh G. Johnson Master of Science Degree 2005 Thesis and Abstract...and Typical Winter Depressive Symptoms and Responsiveness to Light Therapy , Cognitive - Behavioral Therapy , or Combination Treatment 5a. CONTRACT NUMBER...entitled: “Atypical and Typical Winter Depressive Symptoms and Responsiveness to Light Therapy , Cognitive - Behavioral Therapy , or

  6. Efficacy and safety of switching to latanoprost 0.005%–timolol maleate 0.5% fixed-combination eyedrops from an unfixed combination for 36 months

    Directory of Open Access Journals (Sweden)

    Inoue K

    2014-07-01

    Full Text Available Kenji Inoue,1 Ryoko Okayama,1 Risako Higa,1 Goji Tomita2 1Inouye Eye Hospital, Tokyo, 2Second Department of Ophthalmology, Toho University School of Medicine, Tokyo, Japan Purpose: We prospectively investigated the intraocular pressure (IOP-reducing effect, the visual field-maintenance effect, and the adverse reactions caused by administration of ­latanoprost/timolol maleate fixed-combination eyedrops for 3 years.Subjects and methods: The subjects were 162 patients (162 eyes with glaucoma or ocular hypotension who were using latanoprost and timolol maleate eyedrops concomitantly. The latanoprost and timolol maleate eyedrop regimen was discontinued without any washout period and subsequently changed to a latanoprost–timolol maleate fixed-combination eyedrop regimen. IOP values before the change and at 6, 12, 18, 24, 30, and 36 months after the change were measured and compared. The Humphrey visual field test was conducted before the change and at 12, 24, and 36 months after the change, and mean-deviation values were compared. Adverse reactions were assessed at every checkup.Results: The IOPs before the change and at 6–36 months after the change were 15.2±3.3 mmHg and 14.3–15.2 mmHg, respectively, and a significant decrease was observed at 36 months after the change (P<0.01. Mean-deviation values before the change and at 12–36 months after the change were –9.11±6.94 dB and –10.08 to -9.22 dB, respectively, and these values were not significantly different (P=0.2148. Within the 36-month period, the eyedrops were discontinued because of insufficient IOP decrease in 33 cases (20.4% and adverse reactions in eleven cases (6.8%.Conclusion: IOP and the visual field were maintained for 3 years when a latanoprost and timolol maleate eyedrop regimen was changed to a latanoprost–timolol maleate fixed-combination eyedrop regimen. However, administration of the latanoprost–timolol maleate fixed-combination eyedrops was discontinued in

  7. Combined statin-fibrate therapy-induced rhabdomyolysis: Case report

    Directory of Open Access Journals (Sweden)

    Jozić Tanja L.

    2014-01-01

    Full Text Available Introduction Rhabdomyolysis is a rare, but serious and potentially fatal adverse reaction of the statin application that may be developed in any time of therapy. It is characterized by massive destruction of muscles associated with the large increase of creatine kinase (CK leading to myoglobinuria and potential acute renal failure. Combined statin-fibrate therapy increases the risk of rhabdomyolysis, especially in elderly and diabetic patients. Case report An 81-year-old male was admitted to Coronary Care Unit of the Emergency Center, Clinical Center of Serbia (CCS with the clinical picture and electrocardiogram of the acute anterior wall myocardial infarction complicated with pulmonary edema. Laboratory tests on admission showed higher elevated values of serum creatinine 179 μmol/L and BUN 9.2 mmol/L (eGFR 32 mL/min/1.73m2, CK 309 U/L (on day 2: 3476 U/L and mixed hyperlipidemia (total cholesterol 10.3 mmol/L, HDL 2.26 mmol/L, TG 4.85 mmol/L. The patient was treated with thrombolysis medication therapy (Alteplase, anticoagulant and dual antiplatelet therapy, diuretics, organic nitrates, angiotensin-converting enzyme (ACE inhibitors, antibiotics, and proton pump inhibitors. During seven days, his therapy included combined pravastatin 20 mg and fenofibrate (160 mg, which was discontinued due to pains and weakness of muscles and significantly elevated CC to 7080 U/L (upper limit 200 U/L, but no significant deterioration of renal function was observed. Discontinuation of therapy resulted in CC level normalization and improvement of clinical condition. Conclusion Combined statin and fibrate therapy requires strict clinical control and monitoring of CK i transaminases. Four-time or higher increase of CK requires discontinuation of therapy. In addition, patients are advised to report immediately any pains in muscles, sensibility, weakness or cramps.

  8. Efficacy and safety of fixed-ratio combination of insulin degludec and liraglutide (IDegLira) for the treatment of type 2 diabetes

    DEFF Research Database (Denmark)

    Vedtofte, Louise; Knop, Filip K; Vilsbøll, Tina

    2017-01-01

    INTRODUCTION: Type 2 diabetes (T2D) is a progressive disease with increasing prevalence in most countries. The majority of patients with T2D have inadequate glycaemic control, which increases the risk of diabetic complications later in life. New therapies with improved safety profiles are required...... to tackle the progressive nature of T2D. Areas covered: The efficacy and safety profile of IDegLira - a once-daily, fixed-ratio combination of insulin degludec and liraglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), for the treatment of T2D - has been extensively evaluated. IDegLira's phase 3...... clinical trial programme builds upon the clinical programmes of its mono-components, and their cardiovascular outcomes trials. The results are described here, focusing on different patient populations and compared with alternative insulin regimens. Expert opinion: IDegLira provides superior glycaemic...

  9. [Ozone therapy combined with sulfasalazine delivered via a colon therapy system for treatment of ulcerative colitis].

    Science.gov (United States)

    Geng, Yan; Wang, Wei; Ma, Qiang; Peng, Li-qiong; Liang, Zhong-hui

    2010-12-01

    To assess the therapeutic effect of ozone therapy combined with sulfasalazine sulfasalazine delivered via a colon therapy system in the treatment of distal ulcerative colitis. This prospective randomized controlled clinical trial involved 54 patients with mild to moderate active distal ulcerative colitis, who were randomize into 3 groups in accordance with the inclusion criteria (n=18). Each group was given sulfasalazine at the daily dose of 2 g, and in colon therapy group and ozone therapy plus sulfasalazine therapy group, sulfasalazine was delivered via a colon therapy system on a daily basis; the control group received sulfasalazine via retention enema only. At 0, 2, and 4 weeks of the treatment, colonoscopy was performed to evaluate the disease activity, and biopsy samples were obtained at 0 and 4 weeks for histological examination. In comparison with colon therapy group and control group, ozone therapy plus colon therapy resulted in more rapid alleviation of the clinical symptoms and better histological improvement without any adverse effects. Ozone therapy combined with sulfasalazine delivered via a colon therapy system is feasible and effective for treatment of ulcerative colitis.

  10. Combined and alternating paracetamol and ibuprofen therapy for febrile children.

    Science.gov (United States)

    Wong, Tiffany; Stang, Antonia S; Ganshorn, Heather; Hartling, Lisa; Maconochie, Ian K; Thomsen, Anna M; Johnson, David W

    2014-09-01

    Health professionals frequently recommend fever treatment regimens for children that either combine paracetamol and ibuprofen or alternate them. However, there is uncertainty about whether these regimens are better than the use of single agents, and about the adverse effect profile of combination regimens. To assess the effects and side effects of combining paracetamol and ibuprofen, or alternating them on consecutive treatments, compared with monotherapy for treating fever in children. In September 2013, we searched Cochrane Infectious Diseases Group Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; LILACS; and International Pharmaceutical Abstracts (2009-2011). We included randomized controlled trials comparing alternating or combined paracetamol and ibuprofen regimens with monotherapy in children with fever. One review author and two assistants independently screened the searches and applied inclusion criteria. Two authors assessed risk of bias and graded the evidence independently. We conducted separate analyses for different comparison groups (combined therapy versus monotherapy, alternating therapy versus monotherapy, combined therapy versus alternating therapy). Six studies, enrolling 915 participants, are included. Compared to giving a single antipyretic alone, giving combined paracetamol and ibuprofen to febrile children can result in a lower mean temperature at one hour after treatment (MD -0.27 °Celsius, 95% CI -0.45 to -0.08, two trials, 163 participants, moderate quality evidence). If no further antipyretics are given, combined treatment probably also results in a lower mean temperature at four hours (MD -0.70 °Celsius, 95% CI -1.05 to -0.35, two trials, 196 participants, moderate quality evidence), and in fewer children remaining or becoming febrile for at least four hours after treatment (RR 0.08, 95% CI 0.02 to 0.42, two trials, 196 participants, moderate quality evidence). Only one trial assessed a

  11. APPROACHES TO COMBINED THERAPY OF ACUTE INTESTINAL INFECTIONS IN CHILDREN

    Directory of Open Access Journals (Sweden)

    N.G. Soboleva

    2010-01-01

    Full Text Available The results of combined therapy of acute intestinal infections in children with lactulose and pancreatine in prebiotic dose are discussed in this article. Authors showed advantages of combined treatment: significant shortening of terms of symptoms stopping and children’s recovery.Key words: children, acute intestinal infections, lactulose, pancreatine.(Voprosy sovremennoi pediatrii — Current Pediatrics. – 2010;9(3:102-106

  12. Therapeutic Cancer Vaccines in Combination with Conventional Therapy

    OpenAIRE

    Mads Hald Andersen; Niels Junker; Eva Ellebaek; Inge Marie Svane; Per thor Straten

    2010-01-01

    The clinical efficacy of most therapeutic vaccines against cancer has not yet met its promise. Data are emerging that strongly support the notion that combining immunotherapy with conventional therapies, for example, radiation and chemotherapy may improve efficacy. In particular combination with chemotherapy may lead to improved clinical efficacy by clearing suppressor cells, reboot of the immune system, by rendering tumor cells more susceptible to immune mediated killing, or by activation o...

  13. Risks and safety of combination therapy for hypothyroidism.

    Science.gov (United States)

    Jonklaas, Jacqueline

    2016-08-01

    Hypothyroidism is currently a condition that can be treated, but not cured. Although levothyroxine reverses stigmata of hypothyroidism in most individuals, some patients feel dissatisfied with 'monotherapy', and this has stimulated interest in 'combination therapy' with both levothyroxine and liothyronine. A search of PubMed was conducted using terms including hypothyroidism, treatment, benefits, risks, and safety. Based on the articles identified, the body of evidence regarding the efficacy of traditional levothyroxine is reviewed. Concerns with levothyroxine therapy including impaired quality of life in treated patients, thyroxine-predominant hormone ratios, and inadvertent iatrogenic thyroid disease are discussed. The trials of combination therapy performed since 1999 were reviewed. The heterogeneity of these trials, both in terms of design and results, is discussed. The potential for new trials to determine whether combination therapy can reverse the dissatisfaction associated with monotherapy, while avoiding non-physiologic hormone ratios, inadvertent thyrotoxicosis, and unacceptable side effects is discussed. Expert commentary: Research regarding which therapy fully reverses hypothyroidism at a tissue and cellular level is ongoing. The field would be advanced by the development of an extended release preparation of liothyronine. In the future regeneration of functional thyroid follicles from stem cells may offer hope for curing hypothyroidism.

  14. Therapeutic Advances using Combinational Therapy in the Treatment of Glioblastoma

    DEFF Research Database (Denmark)

    Staberg, Mikkel

    2017-01-01

    Glioblastoma is the most malignant brain tumor in adults. Median survival is only about 15 months despite aggressive treatment, consisting of surgery followed by radio- and chemotherapy, stressing the need for new therapies. Development of glioblastoma is thought to be a result of both genetic...... of glioblastoma cells, an effect that is even more pronounced when combined with traditional chemotherapeutic agents. The EGFR and Notch pathways are shown to be of great importance for glioblastoma cell survival and for the formation of new blood vessels, a process known as angiogenesis. Results presented herein...... suggests that targeting redundant signaling pathways can overcome required or initial treatment resistance, thus leading to improved tumor cell elimination. We hypothesize that future therapies will likely be a result of combination therapies for glioblastoma patients based on their molecular tumor profile...

  15. Adverse Event Monitoring of Artemesinin Combination Therapy in ...

    African Journals Online (AJOL)

    Artemesinin combination therapies (ACTs) are first line antimalarial drugs in malaria endemic regions of the world as recommended by the World Health Organization. ACTs are relatively new in Nigeria and there is little experience with their use. The pharmacovigilance of ACT drugs has been advocated in African countries ...

  16. Combination therapy in patients with benign prostatic hyperplasia

    Directory of Open Access Journals (Sweden)

    Bojan Tršinar

    2006-11-01

    Full Text Available Background: The purpose of observational program of patients with lower urinary tract symptoms (LUTS because of benign prostatic hyperplasia (BPH (LUTS/BPH was to acquire additional pharmaco-epidemiological data on the safety and efficacy of combination therapy with finasteride and tamsulosin.Methods: Observational program of men with BPH was conducted in urological outpatient clinics in Slovenia from April 2004 until November 2005. In open-label, non-interventional program 1173 patients were observed, who had been treated because of LUTS/BPH with combination therapy with finasteride and tamsulosin, in the framework of common treatment. At baseline and after six months of treatment for each patient the International Prostatic Symptom Score (IPSS questionnaire and assessment of quality of life (QL were filled in. In addition, urinary flow rate and prostate volume were determined. Adverse effects of drugs were reported spontaneously. For statistical analysis the Student’s t-test was performed.Results: Combination therapy with finasteride and tamsulosin was well tolerated. 89 (7.6 % patients discontinued with medication because of lack of efficacy or because of adverse effects of drugs. Symptom score, assessment of quality of patients’ lives and volume of prostates were significantly lower (p < 0.0001, while urinary flow rate was significantly higher (p < 0.0001 after six months of treatment with finasteride and tamsulosin.Conclusions: Combination therapy of patients with LUTS/BPH with finasteride and tamsulosin is effective and safe.

  17. for assessing efficacy of artemisinin combination therapy against ...

    African Journals Online (AJOL)

    SD Bioline malaria antigen Pf (HRP-2/pLHD) for assessing efficacy of artemisinin combination therapy against Plasmodium falciparum in pediatric patients in the Democratic Republic of the Congo. ... Methods: Five hundred and one patients with malaria symptoms were screened for P. falciparum in Kinshasa, DRC.

  18. Is Chloroquine better than Artemisinin combination therapy as first ...

    African Journals Online (AJOL)

    The current case management and drug policy of malaria in Nigeria recommended by the Federal ministry of health may not be appropriate for all age categories. This suspicion was tested by running a cost effectiveness analysis of two possible and alternative strategies: Artemisinin Combination Therapy (ACT) or ...

  19. Smoking Intervention: A Combination Therapy Approach to Cessation.

    Science.gov (United States)

    Glover, Penny Neathery

    1993-01-01

    Provides an overview of the Start SMART smoking cessation program which combines nicotine withdrawal therapy with behavior modification. The Start SMART program provides seven, intensive one-hour group sessions that are shown to be a most effective intervention with a specific population--motivated, yet highly dependent smokers. (GLR)

  20. Use of Artemisinin- Combination Therapies in Port Harcourt ...

    African Journals Online (AJOL)

    The World Health Organization (WHO) recommends the use of Artemisinin- based combination therapies (ACTs) as the first line of treatment for malaria in Sub –Saharan Africa. This study was carried out to determine the pattern of use of ACTs in Port Harcourt so as to identify problems associated with ACTS use and to ...

  1. Predicting the Toxicity of Adjuvant Breast Cancer Drug Combination Therapy

    Science.gov (United States)

    2013-03-01

    Combination With Trastuzumab in Patients With HER2-Positive, Metastatic Breast Cancer Recruiting No Results Available NO Drug: Lapatinib|Drug: Herceptin ...Trastuzumab ( Herceptin ) -Refractory, Metastatic Breast Cancer Active, not recruiting No Results Available NO Drug: Capecitabine|Drug: Lapatinib Lapatinib...Lapatinib Plus Herceptin With or Without Endocrine Therapy Recruiting No Results Available NO Drug: Herceptin |Drug: Lapatinib|Drug: Letrozole

  2. Atorvastatin/trimetazidine combination therapy in patients with ...

    African Journals Online (AJOL)

    Purpose: To explore the outcomes and safety of atorvastatin/trimetazidine combination therapy in patients with chronic cardiac failure. Methods: A total of 144 patients with chronic cardiac failure were divided into test group (n = 72) and control group (n = 72). In addition to conventional anti-heart failure treatment, all patients ...

  3. Combination Drug Therapy for Benign Prostatic Hyperplasia (BPH ...

    African Journals Online (AJOL)

    BPH symptom reduction and shrinkage of prostate size by the use of a combination of alpha adrenergic uroselective blocker (Tamsulosin) and 5 alpha iso-enzyme inhibitor (Dutasteride) is a first option of therapy in the management of BPH especially in those cases that are surgical risks with the category of mild to moderate ...

  4. 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.

  5. Combined in situ zymography, immunofluorescence, and staining of iron oxide particles in paraffin-embedded, zinc-fixed tissue sections.

    Science.gov (United States)

    Haeckel, Akvile; Schoenzart, Lena; Appler, Franziska; Schnorr, Joerg; Taupitz, Matthias; Hamm, Bernd; Schellenberger, Eyk

    2012-01-01

    Superparamagnetic iron oxide particles are used as potent contrast agents in magnetic resonance imaging. In histology, these particles are frequently visualized by Prussian blue iron staining of aldehyde-fixed, paraffin-embedded tissues. Recently, zinc salt-based fixative was shown to preserve enzyme activity in paraffin-embedded tissues. In this study, we demonstrate that zinc fixation allows combining in situ zymography with fluorescence immunohistochemistry (IHC) and iron staining for advanced biologic investigation of iron oxide particle accumulation. Very small iron oxide particles, developed for magnetic resonance angiography, were applied intravenously to BALB/c nude mice. After 3 hours, spleens were explanted and subjected to zinc fixation and paraffin embedding. Cut tissue sections were further processed to in situ zymography, IHC, and Prussian blue staining procedures. The combination of in situ zymography as well as IHC with subsequent Prussian blue iron staining on zinc-fixed paraffin-embedded tissues resulted in excellent histologic images of enzyme activity, protease distribution, and iron oxide particle accumulation. The combination of all three stains on a single section allowed direct comparison with only moderate degradation of fluorescein isothiocyanate-labeled substrate. This protocol is useful for investigating the biologic environment of accumulating iron oxide particles, with excellent preservation of morphology.

  6. Combined in Situ Zymography, Immunofluorescence, and Staining of Iron Oxide Particles in Paraffin-Embedded, Zinc-Fixed Tissue Sections

    Directory of Open Access Journals (Sweden)

    Eyk Schellenberger

    2012-09-01

    Full Text Available Superparamagnetic iron oxide particles are used as potent contrast agents in magnetic resonance imaging. In histology, these particles are frequently visualized by Prussian blue iron staining of aldehyde-fixed, paraffin-embedded tissues. Recently, zinc salt-based fixative was shown to preserve enzyme activity in paraffin-embedded tissues. In this study, we demonstrate that zinc fixation allows combining in situ zymography with fluorescence immunohistochemistry (IHC and iron staining for advanced biologic investigation of iron oxide particle accumulation. Very small iron oxide particles, developed for magnetic resonance angiography, were applied intravenously to BALB/c nude mice. After 3 hours, spleens were explanted and subjected to zinc fixation and paraffin embedding. Cut tissue sections were further processed to in situ zymography, IHC, and Prussian blue staining procedures. The combination of in situ zymography as well as IHC with subsequent Prussian blue iron staining on zinc-fixed paraffin-embedded tissues resulted in excellent histologic images of enzyme activity, protease distribution, and iron oxide particle accumulation. The combination of all three stains on a single section allowed direct comparison with only moderate degradation of fluorescein isothiocyanate–labeled substrate. This protocol is useful for investigating the biologic environment of accumulating iron oxide particles, with excellent preservation of morphology.

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

    Directory of Open Access Journals (Sweden)

    O'Brien J

    2013-02-01

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

  8. Synergistic combination dry powders for inhaled antimicrobial therapy

    Science.gov (United States)

    Heng, Desmond; Lee, Sie Huey; Teo, Jeanette; Ng, Wai Kiong; Chan, Hak-Kim; Tan, Reginald B. H.

    2013-06-01

    Combination products play an important role in medicine as they offer improved clinical effectiveness, enhanced patient adherence, and reduced administrative costs. In combination antimicrobial therapy, the desired outcome is to extend the antimicrobial spectrum and to achieve a possible synergistic effect. However, adverse antagonistic species may sometimes emerge from such combinations, leading to treatment failure. Therefore, it is crucial to screen the drug candidates for compatibility and possible antagonistic interactions. This work aims to develop a novel synergistic dry powder inhaler (DPI) formulation for antimicrobial combination therapy via the pulmonary route. Binary and ternary combinations were prepared via spray drying on a BUCHI® Nano Spray Dryer B-90. All powders were within the respirable size range, and were consisted of spherical particles that were slightly corrugated. The powers yielded fine particle fractions (of the loaded dose) of over 40% when dispersed using an Aerolizer® DPI at 60 L/min. Time-kill studies carried out against common respiratory tract pathogenic bacteria Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumonia and Acinetobacter baumannii at 1x the minimum inhibitory concentration (MIC) over 24 hours revealed no antagonistic behavior for both combinations. While the interactions were generally found to be indifferent, a favorable synergistic effect was detected in the binary combination when it was tested against Pseudomonas aeruginosa bacteria.

  9. THE ROLE OF S-AMLODIPINE IN ARTERIAL HYPERTENSION THERAPY WITH COMBINATION OF CALCIUM CHANNEL BLOCKERS AND BETA-BLOCKERS

    Directory of Open Access Journals (Sweden)

    M. A. Maksimova

    2013-01-01

    Full Text Available Aim. To study efficacy and safety of calcium channel blocker, S-amlodipine, in combination with β-blocker, atenolol, in patients with arterial hypertension (HT 1-2 degree com- pared to fixed combination of racemic amlodipine and atenolol.Material and methods. Patients (n=31, 7 men and 24 women with HT 1–2 degree were included into the study. The patients were randomized into two groups by the com- binations sequence. Treatment with each combination lasted 4 weeks. Office blood pressure (BP was assessed at baseline and at the end of the treatment periods, possible side effects were registered.Results. All patients completed the study. Both combination of S-amlodipine+atenolol and fixed combination of racemic amlodipine+atenolol reduced systolic (in average, -15.9 and -12.7 mm Hg, respectively and diastolic (in average, -7.3 and -5.3 mmHg, respectively BP significantly. Heart rate also decreased during therapy (in average, -3 and -4 bt/min, respectively. The differences between combinations BP and heart rate effects were not significant. 8 and 16 adverse events were registered during S-amlodipine+atenolol and racemic amlodipine+atenolol therapies, respectively Conclusion. Combination of S-amlodipine+atenolol, as well as combination of racemic amlodipine+atenolol are effective in the treatment of patients with HT 1-2 degree, however combination with S-amlodipine has less number of adverse events.

  10. A fixed combination of hydrochlorothiazide and amiloride for the treatment of essential hypertension.

    Science.gov (United States)

    Ruilope, L; Alcazar, J M; Diaz, V P; Jarillo, M D; Millet, V G; Rodicio, J L

    1980-01-01

    The combination of hydrochlorothiazide and amiloride has been used in a group of patients diagnosed as having essential hypertension. Sixty-five percent of the patients for whom dietary restrictions did not achieve a reduction in blood pressure were initially controlled with this combination; the addition of a second or third drug was required by the remaining patients. During the six-month follow-up, the control of blood pressure was satisfactory with increased drug requirements, but the diuretic had to be discontinued in 12 patients because of side effects.

  11. A fixed-dose combination of memantine extended-release and donepezil in the treatment of moderate-to-severe Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Deardorff WJ

    2016-10-01

    Full Text Available William James Deardorff, George T Grossberg Department of Psychiatry, St Louis University School of Medicine, St Louis, MO, USA Abstract: Currently available therapies for the treatment of Alzheimer’s disease (AD consist of cholinesterase inhibitors (ChEIs, such as donepezil, and the N-methyl-D-aspartate receptor antagonist memantine. In December 2014, the US Food and Drug Administration approved Namzaric™, a once-daily, fixed-dose combination (FDC of memantine extended-release (ER and donepezil for patients with moderate-to-severe AD. The FDC capsule is bioequivalent to the coadministered individual drugs, and its bioavailability is similar when taken fasting, with food, or sprinkled onto applesauce. The combination of memantine and ChEIs in moderate-to-severe AD provides additional benefits to ChEI monotherapy across multiple domains and may delay the time to nursing home admission. A dedicated study of memantine ER compared to placebo in patients on a stable dose of a ChEI found statistically significant benefits on cognition and global status but not functioning. Treatment with memantine ER and donepezil is generally well tolerated, although higher doses of ChEIs are associated with more serious adverse events such as vomiting, syncope, and weight loss. Potential advantages of the FDC include a simpler treatment regimen, reduction in pill burden, and the ability to sprinkle the capsule onto soft foods. Patients who may benefit from the FDC include those with significant dysphagia, a history of poor compliance, or limited caregiver interaction. However, available evidence that these advantages would increase treatment adherence and persistence is conflicting, meaning that the added cost of switching patients from generic options to an FDC may not always be justified. Keywords: Alzheimer’s disease, cholinesterase inhibitor, donepezil, fixed-dose combination, memantine

  12. Role of olmesartan in combination therapy in blood pressure control and vascular function

    Directory of Open Access Journals (Sweden)

    Carlos M Ferrario

    2010-08-01

    Full Text Available Carlos M Ferrario, Ronald D SmithWake Forest University School of Medicine, Winston-Salem, North Carolina, USAAbstract: Angiotensin receptor blockers have emerged as a first-line therapy in the management of hypertension and hypertension-related comorbidities. Since national and international guidelines have stressed the need to control blood pressure to <140/90 mmHg in uncomplicated hypertension and <130/80 mmHg in those with associated comorbidities such as diabetes or chronic kidney disease, these goal blood pressures can only be achieved through combination therapy. Of several drugs that can be effectively combined to attain the recommended blood pressure goals, fixed-dose combinations of angiotensin receptor blockers and the calcium channel blocker amlodipine provide additive antihypertensive effects associated with a safe profile and increased adherence to therapy. In this article, we review the evidence regarding the beneficial effects of renin–angiotensin system blockade with olmesartan medoxomil and amlodipine in terms of blood pressure control and improvement of vascular function and target organ damage.Keywords: amlodipine, angiotensin receptor blockers, angiotensin-converting enzyme 2, hypertension, renin–angiotensin system

  13. Precision medicine and personalized breast cancer: combination pertuzumab therapy

    Directory of Open Access Journals (Sweden)

    Reynolds K

    2014-03-01

    Full Text Available Kerry Reynolds, Sasmit Sarangi, Aditya Bardia, Don S Dizon Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA Abstract: Trastuzumab (Herceptin, a monoclonal antibody directed against the human epidermal growth-factor receptor 2 (HER2, is the poster child for antibody-based targeted therapy in breast cancer. Pertuzumab, another humanized monoclonal antibody, binds to a different domain of HER2 and prevents the formation of HER2:HER3 dimers, which is the most potent heterodimer in the HER family. The combination of trastuzumab and pertuzumab has synergistic activity, and is associated with improved clinical outcomes. The US Food and Drug Administration (FDA approved pertuzumab in combination with trastuzumab-based chemotherapy originally as first-line therapy for metastatic HER2-positive breast cancer in 2012, and more recently as neoadjuvant therapy for localized disease in 2013. Pertuzumab is the first neoadjuvant drug to receive accelerated approval by the FDA based on pathological complete response as the primary end point. In this article, we review the mechanism of action, pharmacokinetics, clinical efficacy, safety, and current role of pertuzumab in the management of breast cancer, as well as ongoing clinical trials and future directions regarding the utility of pertuzumab as a personalized therapeutic option for HER2-positive breast cancer. In the coming years, we anticipate increased utilization of neoadjuvant trials for drug development, biomarker discovery, and validation, and envision conduct of personalized breast cancer clinics in which therapies will be routinely selected based on genetic alterations in the tumor. Regardless of the targeted therapy combinations employed based on tumor genomic profile, trastuzumab and pertuzumab will likely continue to form the backbone of the personalized regimen for HER2-positive breast cancer. Keywords: pertuzumab, HER2 breast cancer, personalized therapy

  14. Effectiveness of medication / auricular therapy / phyto-therapy combination in the treatment of hypertensive patients

    Directory of Open Access Journals (Sweden)

    José Ramón Martínez Pérez

    2015-10-01

    Full Text Available Background: hypertension is one of the main cardiovascular risk factors, so its control improves the life expectancy of patients.Objective: to assess the effects of a treatment combining medication with auricular therapy and phyto-therapy in hypertensive patients assisted at the health area of ”Romárico Oro” Polyclinic, in Puerto Padre, Las Tunas province.Methods: an intervention study was carried out in 68 hypertensive patients of the health area of “Romárico Oro” Polyclinic in Puerto Padre from April, 2013 to April, 2014. The patients were distributed at random into two equal groups; the first received medication combined with auricular therapy and phyto-therapy, while the second one received only medication. The statistical analysis was done by means of Statistic system, t-student and Chi-Square tests were used and p< or =0.05 was considered as level of statistical significance.Results: by the end of the intervention, 73, 53% of the patients of the group with the combination of drug treatment and auricular therapy and phyto-therapy were controlled. In this group, the diastolic filling pressure diminished to 2, 2 mm Hg and the systolic gradient to 3, 66 mm, regarding the group treated only with drugs. Only one patient, representing the 2, 94% showed adverse reaction to the natural and traditional treatment.Conclusions: the combination of medication with auricular therapy and phyto-therapy proved to be effective, corroborated by a significant decrease of quantity of crisis, diastolic and systolic filling pressure values and increase of number of patients with their disease controlled; the report of only one complication shows the innocuousness of the auricular therapy and phyto-therapy treatment.

  15. A review of the new GLP-1 receptor agonist/basal insulin fixed-ratio combination products.

    Science.gov (United States)

    Nuffer, Wesley; Guesnier, Ashley; Trujillo, Jennifer M

    2018-03-01

    There have been several new treatment approaches established for the management of hyperglycemia in type 2 diabetes (T2D), with treatment guidelines listing both glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and basal insulin therapies as considerations for patients who have failed to control their blood glucose with oral antidiabetic agents. New studies have highlighted the importance of initiating combination therapy earlier in the T2D disease process to avoid clinical inertia and prevent the long-term complications arising from uncontrolled diabetes. Until recently, both GLP-1 RAs and basal insulin therapies were only available as single agents, but there are now two combination pen devices that deliver both a GLP-1 RA and basal insulin simultaneously. This article reviews the current clinical evidence evaluating the use of these combination GLP-1 RA/basal insulin preparations to treat T2D, presents both potential benefits as well as possible downsides with the use of these agents, and discusses the current place in therapy these products represent in the management of T2D.

  16. Fixed-Dose Combinations of Pioglitazone and Metformin for Lung Cancer Prevention.

    Science.gov (United States)

    Seabloom, Donna E; Galbraith, Arthur R; Haynes, Anna M; Antonides, Jennifer D; Wuertz, Beverly R; Miller, Wendy A; Miller, Kimberly A; Steele, Vernon E; Miller, Mark Steven; Clapper, Margie L; O'Sullivan, M Gerard; Ondrey, Frank G

    2017-02-01

    Combination treatment with pioglitazone and metformin is utilized clinically in the treatment of type II diabetes. Treatment with this drug combination reduced the development of aerodigestive cancers in this patient population. Our goal is to expand this treatment into clinical lung cancer chemoprevention. We hypothesized that dietary delivery of metformin/pioglitazone would prevent lung adenoma formation in A/J mice in a benzo[a]pyrene (B[a]P)-induced carcinogenesis model while modulating chemoprevention and anti-inflammatory biomarkers in residual adenomas. We found that metformin (500 and 850 mg/kg/d) and pioglitazone (15 mg/kg/d) produced statistically significant decreases in lung adenoma formation both as single-agent treatments and in combination, compared with untreated controls, after 15 weeks. Treatment with metformin alone and in combination with pioglitazone resulted in statistically significant decreases in lung adenoma formation at both early- and late-stage interventions. Pioglitazone alone resulted in significant decreases in adenoma formation only at early treatment intervention. We conclude that oral metformin is a viable chemopreventive treatment at doses ranging from 500 to 1,000 mg/kg/d. Pioglitazone at 15 mg/kg/d is a viable chemopreventive agent at early-stage interventions. Combination metformin and pioglitazone performed equal to metformin alone and better than pioglitazone at 15 mg/kg/d. Because the drugs are already FDA-approved, rapid movement to human clinical studies is possible. Cancer Prev Res; 10(2); 116-23. ©2017 AACR. ©2017 American Association for Cancer Research.

  17. Better Together: Targeted Combination Therapies in Breast Cancer.

    Science.gov (United States)

    Zanardi, Elisa; Bregni, Giacomo; de Braud, Filippo; Di Cosimo, Serena

    2015-12-01

    Recent discoveries both in cell proliferation and survival mechanisms and new antineoplastic agents have led to deep change in the breast cancer treatment paradigm. Nonetheless, all of the progress in knowledge and strategy has not been enough to overcome mechanisms of escape and resistance put in place by the tumor cells. New targeted agents mean new possibilities for combinations, a viable option to try to stop compensatory pathways of tumor growth activated in response to therapeutics. The main challenges in designing a combined therapy come from the variety of subtypes of breast cancer (luminal A, luminal B, HER2-enriched, and basal-like) and from the multitude of pathways each subtype can exploit. Recent research has focused on dual blockade of HER2 (trastuzumab-lapatinib; trastuzumab-pertuzumab) and concomitant blockade of the endocrine driver and other pathways such as the PI3K/AKT/mTOR pathway (everolimus-exemestane), HER2 (trastuzumab/lapatinib-endocrine therapy) and the cell cycle through cyclin-dependent kinase inhibition (letrozole-palbociclib). This combined and personalized approach to treatment needs a profound knowledge of the mechanisms leading to proliferation in each tumor subtype. Deepening our understanding of tumor growth is mandatory to keep improving the efficacy of combination therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. The wider use of fixed-dose combinations emphasizes the need for a global approach to regulatory guideline development

    DEFF Research Database (Denmark)

    Gautam, Yvonne; Bjerrum, Ole Jannik; Schmiegelow, Merete

    2015-01-01

    face the regulatory world: how to improve the role of regulatory science and provide clear quantification in assessment decisions; the role of guidelines and their impact on innovation; and, most important, the question of globalization and how to move toward a more harmonized regulatory system.......A fixed-dose combination (FDC) is a drug product in which two or more separate drug components (active pharmaceutical ingredients) are combined in a single-dosage form. Interest in developing FDCs is increasing in a range of diseases. This project investigated the regulatory environment for FDCs....... It was clear from the results that the current regulatory environment for FDCs lacks consistency. This may create a barrier to innovation moving from the laboratory to the clinic, as companies cannot clearly see the development path requirements. This project also highlighted certain challenges that currently...

  19. Meibomian Gland Features and Conjunctival Goblet Cell Density in Glaucomatous Patients Controlled with Prostaglandin/Timolol Fixed Combinations: A Case Control, Cross-sectional Study.

    Science.gov (United States)

    Agnifili, Luca; Mastropasqua, Rodolfo; Fasanella, Vincenzo; Brescia, Lorenza; Scatena, Barbara; Oddone, Francesco; Mastropasqua, Leonardo

    2018-02-02

    To investigate, using in vivo confocal microscopy (IVCM), the Meibomian gland (MG) features and conjunctival goblet cell density (GCD) in glaucomatous patients controlled with prostaglandin/timolol fixed combinations (PTFCs). In this cross-sectional study, sixty Caucasian patients treated with PTFCs, fifteen with latanoprost+timolol (L+T) unfixed combination, and fifteen controls were enrolled. Patients underwent the Ocular Surface Disease Index (OSDI) questionnaire, tear film break-up time (BUT), corneal staining, Schirmer test I (STI), and IVCM of MGs and goblet cells (GCs). The main outcome measures were: mean Meibomian acinar density (MMAD) and area (MMAA), inhomogeneity of glandular interstice (InI) and acinar wall (InAW), and GCD. PTFCs were: latanoprost/timolol (LTFC; 15 eyes), travoprost/timolol (TTFC; 15), bimatoprost/timolol (BTFC; 15), and preservative free-bimatoprost/timolol (PF-BTFC; 15). Mean time on therapy did not differ among treatments. IVCM documented lower GCD, MMAD and MMAA (PMMAD, MMAA, GCD and greater InI and InAW compared to PF-BTFC (PMMAD (P<0.05). PTFCs were less toxic towards MGs and GCs compared to the L+T unfixed combination, with PF-BTFC presenting the most tolerated profile. These findings should be carefully considered given the role of these structures in the induction of the glaucoma-related ocular surface disease.

  20. Effectiveness of Manual Therapy Combined With Physical Therapy in Treatment of Patellofemoral Pain Syndrome: Systematic Review.

    Science.gov (United States)

    Espí-López, Gemma Victoria; Arnal-Gómez, Anna; Balasch-Bernat, Mercè; Inglés, Marta

    2017-06-01

    The purpose of this study was to conduct a review of randomized controlled trials (RCTs) to determine the treatment effectiveness of the combination of manual therapy (MT) with other physical therapy techniques. Systematic searches of scientific literature were undertaken on PubMed and the Cochrane Library (2004-2014). The following terms were used: "patellofemoral pain syndrome," "physical therapy," "manual therapy," and "manipulation." RCTs that studied adults diagnosed with patellofemoral pain syndrome (PFPS) treated by MT and physical therapy approaches were included. The quality of the studies was assessed by the Jadad Scale. Five RCTs with an acceptable methodological quality (Jadad ≥ 3) were selected. The studies indicated that MT combined with physical therapy has some effect on reducing pain and improving function in PFPS, especially when applied on the full kinetic chain and when strengthening hip and knee muscles. The different combinations of MT and physical therapy programs analyzed in this review suggest that giving more emphasis to proximal stabilization and full kinetic chain treatments in PFPS will help better alleviation of symptoms.

  1. Efficacy and tolerability of fixed-combination brinzolamide/timolol in Latin American patients with open-angle glaucoma or ocular hypertension previously on brimonidine/timolol fixed combination.

    Science.gov (United States)

    Alezzandrini, Arturo; Hubatsch, Douglas; Alfaro, Rene

    2014-09-01

    Fixed-combination glaucoma medications are commonly used to achieve target intraocular pressure (IOP) reduction in patients uncontrolled with monotherapy; however, ocular discomfort associated with eye drops can decrease adherence. This study assessed the efficacy and tolerability of twice-daily fixed-combination brinzolamide 1%/timolol 0.5% (BRINZ/TIM-FC) in Latin American patients transitioned from fixed-combination brimonidine 0.2%/timolol 0.5% (BRIM/TIM-FC) because of insufficient IOP control or treatment intolerance. This 8-week, open-label, prospective study was conducted at six sites in Argentina, Chile, and Mexico. Enrolled patients were aged ≥18 years with open-angle glaucoma (including primary, exfoliative, or pigment-dispersion glaucoma) or ocular hypertension with IOP of 19-35 mmHg in ≥1 eye at baseline (on BRIM/TIM-FC). Patients self-administered BRINZ/TIM-FC to both eyes at 8 a.m. and 8 p.m. daily for 8 weeks. The primary and secondary efficacy endpoints were mean IOP change from baseline at week 8 and percentage of patients achieving target IOP (≤18 mmHg) at week 8, respectively. Exploratory endpoints included patient and investigator preference for treatment at week 8. Adverse events (AEs) were assessed as the safety endpoint. Fifty patients (mean ± SD age, 66.7 ± 11.5 years) received BRINZ/TIM-FC, and 49 were included in the intent-to-treat population. Mean ± SD IOP was significantly reduced from baseline after 8 weeks of treatment with BRINZ/TIM-FC (-3.6 ± 3.0 mmHg; P < 0.0001, Wilcoxon signed-rank test; 17.1% reduction). Overall, 55.3% of patients achieved IOP ≤18 mmHg at week 8. Significantly more patients (89.4%) and investigators (95.7%) preferred BRINZ/TIM-FC to BRIM/TIM-FC (both P < 0.0001, exact binomial test). Of the 13 AEs observed, 8 were related to BRINZ/TIM-FC; the most common treatment-related AEs were eye irritation (n = 4) and abnormal sensation in the eye (n = 2). BRINZ/TIM-FC provides an

  2. ECONOMIC EVALUATION OF COMBINED THERAPY OF ARTERIAL HYPERTENSION BY MARKOV’S MODELING

    Directory of Open Access Journals (Sweden)

    N. S. Maksimchuk-Kolobova

    2015-09-01

    Full Text Available Aim. To evaluate the economic effectiveness of the combined two-drug antihypertensive therapy in patients with arterial hypertension (HT and high cardiovascular risk by Markov’s modeling.Material and methods. Patients (n= 65; 19 males and 46 females with essential HT accompanied by metabolic disorders, history of previous ineffective antihypertensive therapy were included into the study. Patients were randomized into 2 groups. Group V/A was treated with valsartan and amlodipine in fixed-dose combinations of 160/5 and 160/10 mg depending on blood pressure (BP level. Patients of group L/A were treated with losartan 100 mg and amlodipine 5 or 10 mg daily. Treatment duration was 24 weeks. Changes in BP level, and left ventricular hypertrophy (LVH regression were assessed. Economic evaluation was performed on the basis of modeling with specialized software Decision Tree 4.xla.Results. Effect of the two variants of combination therapy on LVH was used to estimate treatment effectiveness and to build the model. Patients were distributed according to the left ventricular mass (LVM at baseline and after 24 weeks of therapy. Significant decrease in LVM was observed in V/A group: from 225.1±71.7 to 186.3±44.5 g (p<0.05. There was no LVM dynamics in L/A group. The model took into account economic and frequency factors for 10 years forecast. V/A therapy is able to prevent 94 deaths, 22 strokes, and 64 myocardial infarction per 1000 patients. Absence of need in treatment of these prevented events can save about 5.5 million RUR for every 1000 patients. It would reduce the total costs per patient during 10 years. V/A therapy is able to save maximal number of quality adjusted life years (QALY due to LVM regression (5.016 years. L/A combination is the most economical variant of pharmacotherapy due to low cost of treatment (16.491.25 RUR per 1 QALY. It would take 286.698.7 RUR additionally for one additional QALY in the treatment with V/A, and it is

  3. Natural compounds and combination therapy in colorectal cancer treatment.

    Science.gov (United States)

    Rejhová, A; Opattová, A; Čumová, A; Slíva, D; Vodička, P

    2018-01-20

    Colorectal cancer (CRC) therapy using conventional chemotherapeutics represents a considerable burden for the patient's organism because of high toxicity while the response is relatively low. Our review summarizes the findings about natural compounds as chemoprotective agents for decreasing risk of CRC. It also identifies natural compounds which possess anti-tumor effects of various characteristics, mainly in vitro on colorectal cell lines or in vivo studies on experimental models, but also in a few clinical trials. Many of natural compounds suppress proliferation by inducing cell cycle arrest or induce apoptosis of CRC cells resulting in the inhibition of tumor growth. A novel employment of natural substances is a so-called combination therapy - administration of two or more substances - conventional chemotherapeutics and a natural compound or more natural compounds at a time. Some natural compounds may sensitize to conventional cytotoxic therapy, reinforce the drug effective concentration, intensify the combined effect of both administered therapeutics or exert cytotoxic effects specifically on tumor cells. Moreover, combined therapy by targeting multiple signaling pathways, uses various mechanisms to reduce the development of resistance to antitumor drugs. The desired effect could be to diminish burden on the patient's organism by replacing part of the dose of a conventional chemotherapeutic with a natural substance with a defined effect. Many natural compounds are well tolerated by the patients and do not cause toxic effects even at high doses. Interaction of conventional chemotherapeutics with natural compounds introduces a new aspect in the research and therapy of cancer. It could be a promising approach to potentially achieve improvements, while minimizing of adverse effects associated with conventional chemotherapy. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  4. Orthodontics-surgical combination therapy for Class III skeletal malocclusion

    Directory of Open Access Journals (Sweden)

    M S Ravi

    2012-01-01

    Full Text Available The correction of skeletal Class III malocclusion with severe mandibular prognathism in an adult individual requires surgical and Othodontic combination therapy. The inter disciplinary approach is the treatment of choice in most of the skeletal malocclusions. A case report of an adult individual with Class III malocclusion, having mandibular excess in sagittal and vertical plane and treated with orthodontics,, bilateral sagittal split osteotomy and Le - Forte I osteotomy for the correction of skeletal, dental and soft tissue discrepancies is herewith presented. The surgical-orthodontic combination therapy has resulted in near-normal skeletal, dental and soft tissue relationship, with marked improvement in the facial esthetics in turn, has helped the patient to improve the self-confidence level.

  5. Cancer treatment: the combination of vaccination with other therapies

    DEFF Research Database (Denmark)

    Andersen, M.H.; Sorensen, R.B.; Schrama, D.

    2008-01-01

    approach to fight cancer, the combination with additional therapy could create a number of synergistic effects. Herein we discuss the possibilities and prospects of vaccination when combined with other treatments. In this regard, cell death upon drug exposure may be immunogenic or non-immunogenic depending...... and endothelial cells. The efficacy of therapeutic vaccination against cancer will over the next few years be studied in settings taking advantage of strategies in which vaccination is combined with other treatment modalities. These combinations should be based on current knowledge not only regarding the biology...... of the cancer cell per se, but also considering how treatment may influence the malignant cell population as well as the immune system Udgivelsesdato: 2008/11...

  6. Blood pressure normalization by fixed perindopril/indapamide combination in hypertensive patients with or without associate metabolic syndrome: results of the OPTIMAX 2 study

    Directory of Open Access Journals (Sweden)

    Jean-Jacques Mourad

    2008-04-01

    Full Text Available Jean-Jacques Mourad1, Dulce Lameira1, Pierre-Jean Guillausseau21APHP, Service de Médecine interne, Hôpital Avicenne, Bobigny, France; 2APHP, Service de Médecine B, Hôpital Lariboisière, et Université Paris, Paris, FranceAbstract: The aim of the observational pharmaco-epidemiological study Optimax II was to seek whether the pre-existence of a metabolic syndrome (MS defi ned by the NCEP-ATP III criteria impacts blood pressure (BP control in hypertensive patients receiving a fixed perindopril/indapamide combination therapy. The primary objective of the study was to compare in patients with and without MS the rate of BP control defined as a systolic BP ≤140 mmHg and a diastolic BP ≤90 mmHg. Patients were prospectively included and the follow-up lasted 6 months. The study population consisted of 24,069 hypertensive patients (56% men; mean age 62 ± 11 years; 18% diabetics; mean BP at inclusion 162 ± 13/93 ± 9 mmHg. MS was found in 30.4% of the patients (n = 7322: 35.2% women and 20.1% men. Three therapeutic subgroups were constituted: Group A, previously untreated, received the combination therapy as initial treatment; Group B, previously treated but with unsatisfactory results and/or treatment intolerance, had its previous treatment switched to perindopril/indapamide; and Group C, previously treated, with good treatment tolerance but uncontrolled BP, received the study treatment in adjunction to the previous one. The normalization rate was 70.3% in group A, 68.4% in Group B, and 64.1% in Group C (p < 0.0001. The pre-existence of MS did not show any significant influence on these rates since BP lowering was –22.7 ± 13.7 (SBP and –12.0 ± 10.0 mmHg (DBP in patients without MS and –22.6 ± 13.3 (SBP and −12.1 ± 9.7 (DBP in those with MS. The results of this study show a significant effect of perindopril/indapamide treatment on systolic BP lowering, whatever the treatment status: initiation, switch, or adjunctive therapy, and

  7. Oxidative stress in malaria and artemisinin combination therapy

    DEFF Research Database (Denmark)

    Kavishe, Reginald A.; Koenderink, Jan B.; Alifrangis, Michael

    2017-01-01

    Artemisinin-based combination therapy (ACT) has been adopted as a strategy to mitigate multidrug resistance to antimalarial monotherapies. ACT combines the rapid and effective but rather short plasma half-life antimalarial action of an artemisinin derivative with a longer acting partner drug....... Although the exact mechanisms of action of artemisinins are not well understood, several studies have proposed multiple cellular targets of artemisinins with involvement of reactive oxygen species (ROS). Most of the currently used ACT partner drugs are also known to involve ROS production...

  8. Response to combination antiretroviral therapy: variation by age

    DEFF Research Database (Denmark)

    Lundgren, Jens

    2008-01-01

    OBJECTIVE: To provide information on responses to combination antiretroviral therapy in children, adolescents and older HIV-infected persons. DESIGN AND SETTING: Multicohort collaboration of 33 European cohorts. SUBJECTS:: Forty-nine thousand nine hundred and twenty-one antiretroviral-naive indiv...... CD4 cell counts, may place this group at increased clinical risk. The poorer virological responses in children may increase the likelihood of emergence of resistance....

  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. Safety of an Oral Fixed Combination of Netupitant and Palonosetron (NEPA): Pooled Data From the Phase II/III Clinical Program.

    Science.gov (United States)

    Aapro, Matti; Hesketh, Paul J; Jordan, Karin; Gralla, Richard J; Rossi, Giorgia; Rizzi, Giada; Palmas, Marco

    2016-04-01

    Standard prophylaxis for chemotherapy-induced nausea and vomiting (CINV) with highly emetogenic and anthracycline-cyclophosphamide-based chemotherapy includes a 5-hydroxytryptamine-3 receptor antagonist, a neurokinin-1 receptor antagonist (NK1RA), and corticosteroid therapy. NEPA is a fixed combination of netupitant and palonosetron. The primary objective of this analysis was to document the safety profile, including cardiac safety, of NEPA + dexamethasone in comparison with current therapies across all phase II/III trials. This pooled analysis was based on data from 3,280 patients in 4 randomized, double-blind clinical trials. Patients were categorized into 1 of 3 pooled groups on the basis of actual treatment received: NEPA + dexamethasone, palonosetron + dexamethasone, and aprepitant + ondansetron/palonosetron + dexamethasone. Safety was assessed by number and frequency of adverse events (AEs) and changes from baseline electrocardiogram measures. Most patients were female and younger than 65 years of age. Demographic characteristics varied among studies and pooled groups. Frequencies of treatment-emergent AEs (TEAEs) and treatment-related AEs (TRAEs) were similar across groups. TEAEs were mostly mild and consistent with expected chemotherapy and disease-related AEs (hematologic events, hair loss, general weakness). TRAEs in ≥2% of patients were headache and constipation. Frequencies of cardiac TEAEs were similar across groups, with QT prolongation (1.6%), tachycardia (1.1%), and dyspnea (0.9%) the most common. Serious cardiac TEAEs were rare. NEPA was well-tolerated, with an AE profile as expected for the regimen. Sample size, demographic characteristics, study design, chemotherapy, and antiemetic regimen differences across the four studies may have contributed to differences in frequencies of neutropenia and alopecia. Adding an NK1RA to a CINV prophylaxis regimen can improve outcomes without additional toxicity. Supportive care for cancer should ideally be

  11. Combination therapy design for maximizing sensitivity and minimizing toxicity.

    Science.gov (United States)

    Matlock, Kevin; Berlow, Noah; Keller, Charles; Pal, Ranadip

    2017-03-22

    Design of personalized targeted therapies involve modeling of patient sensitivity to various drugs and drug combinations. Majority of studies evaluate the sensitivity of tumor cells to targeted drugs without modeling the effect of the drugs on normal cells. In this article, we consider the individual modeling of drug responses to tumor and normal cells and utilize them to design targeted combination therapies that maximize sensitivity over tumor cells and minimize toxicity over normal cells. The problem is formulated as maximizing sensitivity over tumor cell models while maintaining sensitivity below a threshold over normal cell models. We utilize the constrained structure of tumor proliferation models to design an accelerated lexicographic search algorithm for generating the optimal solution. For comparison purposes, we also designed two suboptimal search algorithms based on evolutionary algorithms and hill-climbing based techniques. Results over synthetic models and models generated from Genomics of Drug Sensitivity in Cancer database shows the ability of the proposed algorithms to arrive at optimal or close to optimal solutions in significantly lower number of steps as compared to exhaustive search. We also present the theoretical analysis of the expected number of comparisons required for the proposed Lexicographic search that compare favorably with the observed number of computations. The proposed algorithms provide a framework for design of combination therapy that tackles tumor heterogeneity while satisfying toxicity constraints.

  12. Fixed combination of bimatoprost and timolol in patients with primary open-angle glaucoma or ocular hypertension with inadequate IOP adjustment

    Directory of Open Access Journals (Sweden)

    Gerrett Brief

    2010-09-01

    Full Text Available Gerrett Brief1, Tobias Lammich2, Edgar Nagel3, Sabine Pfennigsdorf4, Christoph W Spraul5, Selwyn Ho61Facharzt für Augenheilkunde, Dortmund, Germany; 2Neubrandenburg, Germany; 3Augenarztpraxis Rudolstadt, Germany; 4Polch, Germany; 5Geiselhart, Ulm, Germany; 6Allergan Europe, Marlow, UKObjective: To assess the efficacy and tolerability of a fixed combination of bimatoprost and timolol (BTFC in a large patient sample in a clinical setting.Methods: In this multicenter, observational, noncontrolled, open-label study, patients (n = 1862 with primary open-angle glaucoma or ocular hypertension were treated with BTFC. Assessments were made at baseline, six weeks, and three months.Results: Prior to starting BTFC, 92.3% of patients were taking other ocular hypotensive medications. In the overall group at three months, mean intraocular pressure was reduced from baseline (21.7 ± 4.5 mmHg and 21.8 ± 4.9 mmHg for the right and left eye, respectively to 16.1 ± 3.0 mmHg for each eye (P < 0.0001. The majority of patients (92% reported no adverse events. The most commonly reported adverse events (in >1% of patients were eye irritation, and ocular and conjunctival hyperemia. Adherence to treatment was generally better than (35.4% or the same as (57.5% with prior therapy. BTFC tolerability was rated as excellent or good by 92.3% of physicians and 85.8% of patients.Conclusions: In a large group of patients with primary open-angle glaucoma or ocular hypertension, treatment with BTFC was associated with consistent reductions in IOP, improved adherence to treatment, and good tolerability.Keywords: bimatoprost, timolol, intraocular pressure, fixed combination, glaucoma

  13. iGlarLixi: A Fixed-Ratio Combination of Insulin Glargine 100 U/mL and Lixisenatide for the Treatment of Type 2 Diabetes.

    Science.gov (United States)

    Goldman, Jennifer; Trujillo, Jennifer M

    2017-11-01

    To review the safety and efficacy of iGlarLixi, a titratable fixed-ratio combination of insulin glargine 100 U/mL (iGlar) and lixisenatide, a glucagon-like peptide-1 receptor agonist. A literature search of MEDLINE for all English-language primary articles through June 2016, using the terms LixiLan, iGlarLixi and insulin glargine and lixisenatide, and a search of abstracts presented at the 2016 Scientific Sessions of the American Diabetes Association were performed. All studies assessing the efficacy and/or safety of iGlarLixi were evaluated. iGlarLixi has been approved in the United States for glycemic control in people with type 2 diabetes (T2D) inadequately controlled with basal insulin (<60 U/d) or lixisenatide. In clinical trials, iGlarLixi was associated with significantly greater reductions from baseline in glycated hemoglobin A 1C (A1C) than iGlar or lixisenatide alone. Reductions in postprandial glucose were also greater with iGlarLixi than with iGlar or lixisenatide. iGlarLixi was weight neutral compared with the weight gain with iGlar and loss with lixisenatide alone, and there was no increase in hypoglycemia with iGlarLixi compared with iGlar despite the greater A1C reduction. Gastrointestinal events, frequently associated with lixisenatide, were less common with iGlarLixi. Potential drawbacks of iGlarLixi include reduced flexibility in dosing and the absence of long-term efficacy and safety data. iGlarLixi is a titratable fixed-ratio combination that shows improved efficacy and comparable or improved safety outcomes relative to its separate constituents, offering an alternative approach to intensification of therapy in T2D.

  14. Azilsartan/chlorthalidone combination therapy for blood pressure control

    Directory of Open Access Journals (Sweden)

    Cheng JW

    2013-05-01

    Full Text Available Judy WM ChengMassachusetts College of Pharmacy and Health Sciences, Brigham and Women's Hospital, Boston, MA, USABackground: Edarbyclor® is a combined angiotensin receptor blocker (ARB and thiazide-like diuretic (azilsartan and chlorthalidone, and was approved on December 20, 2011 by the US Food and Drug Administration (FDA for hypertension management.Objective: To review the pharmacology, pharmacokinetics, efficacy, safety, tolerability, and role of azilsartan plus chlorthalidone for hypertension management.Methods: Peer-reviewed clinical trials, review articles, and relevant treatment guidelines, were identified from the databases MEDLINE and Current Contents (both 1966 to February 15, 2013, inclusive using search terms “azilsartan”, “chlorthalidone”, “pharmacology”, “pharmacokinetics”, “pharmacodynamics”, “pharmacoeconomics”, and “cost-effectiveness”. The FDA website, as well as manufacturer prescribing information, was also reviewed to identify other relevant information.Results: Azilsartan is a new ARB with high affinity for the angiotensin 1 receptor, approved by the FDA for hypertension management. Unlike other ARBs, azilsartan has no clinical data supporting improvement in cardiovascular outcomes, and is not approved for indications other than hypertension, which a select few other ARBs may be used for (eg, diabetic nephropathy and heart failure. Chlorthalidone is a longer acting thiazide-like diuretic that has been demonstrated to improve cardiovascular outcomes. Combination treatment with azilsartan/chlorthalidone is effective for reducing blood pressure. Compared to olmesartan/hydrochlorothiazide and azilsartan/hydrochlorothiazide combinations, azilsartan/chlorthalidone appears to be more efficacious for reducing blood pressure.Conclusions: Azilsartan/chlorthalidone can be considered an antihypertensive therapy option in patients for whom combination therapy is required (blood pressure >20 mmHg systolic or

  15. Drastic therapy for listerial brain abscess involving combined hyperbaric oxygen therapy and antimicrobial agents.

    Science.gov (United States)

    Nakahara, Keiichi; Yamashita, Satoshi; Ideo, Katsumasa; Shindo, Seigo; Suga, Tomohiro; Ueda, Akihiko; Honda, Shoji; Hirahara, Tomoo; Watanabe, Masaki; Yamashita, Taro; Maeda, Yasushi; Yonemochi, Yasuhiro; Takita, Tomohiro; Ando, Yukio

    2014-10-01

    Listeria monocytogenes (L. monocytogenes) is a rare causative pathogen of brain abscess that is often found in immunocompromised patients. Although patients with supratentorial listerial abscesses showed a longer survival with surgical drainage, the standard therapy for patients with subtentorial lesions has not been established. We report herein a patient with supra- and subtentorial brain abscesses caused by L. monocytogenes infection. These abscesses did not respond to antibiotics, and his symptoms gradually worsened. Drainage was not indicated for subtentorial lesions, and the patient was additionally treated with hyperbaric oxygen therapy, which dramatically reduced the volume of abscesses and improved the symptoms. This is the first report of drastic therapy for a patient with listerial brain abscesses involving combined antibiotics and hyperbaric oxygen therapy. The findings suggest that hyperbaric oxygen therapy is a good option for treating patients with deep-seated listerial abscesses and for who surgical drainage is not indicated.

  16. Fixed Field Alternating Gradient Accelerators (FFAG) for Fast Hadron Cancer Therapy

    CERN Document Server

    Keil, Eberhard; Trbojevic, Dejan

    2005-01-01

    Cancer accelerator therapy continues to be ever more prevalent with new facilities being constructed at a rapid rate. Some of these facilities are synchrotrons, but many are cyclotrons and, of these, a number are FFAG cyclotrons. The therapy method of "spot scanning” requires many pulses per second (typically 200 Hz), which can be accomplished with a cyclotron (in contrast with a synchrotron). We briefly review commercial scaling FFAG machines and then discuss recent work on non-scaling FFAGs, which may offer the possibility of reduced physical aperture and a large dynamic aperture. However, a variation of tune with energy implies the crossing of resonances during the acceleration process. A design can be developed such as to avoid intrinsic resonances, although imperfection resonances must still be crossed. Parameters of two machines are presented; a 250 MeV proton therapy accelerator and a 400 MeV carbon therapy machine.

  17. Combining HDAC inhibitors with oncolytic virotherapy for cancer therapy

    Directory of Open Access Journals (Sweden)

    Nakashima H

    2015-11-01

    Full Text Available Hiroshi Nakashima, Tran Nguyen, Ennio Antonio ChioccaDepartment of Neurosurgery, Brigham and Women's Hospital, Boston, MA, USAAbstract: Histone deacetylase (HDAC enzymes play a critical role in the epigenetic regulation of cellular functions and signaling pathways in many cancers. HDAC inhibitors (HDACi have been validated for single use or in combination with other drugs in oncologic therapeutics. An even more novel combination therapy with HDACi is to use them with an oncolytic virus. HDACi may lead to an amplification of tumor-specific lytic effects by facilitating increased cycles of viral replication, but there may also be direct anticancer effects of the drug by itself. Here, we review the molecular mechanisms of anti-cancer effects of the combination of oncolytic viruses with HDACi.Keywords: epigenetics, glioma, oncolytic virus, HDAC inhibitor, HSV-1, cancer

  18. 5-Alpha-Reductase Inhibitors and Combination Therapy.

    Science.gov (United States)

    Füllhase, Claudius; Schneider, Marc P

    2016-08-01

    By inhibiting the conversion from testosterone to dihydrotestosterone 5-Alpha reductase inhibitors (5ARIs) are able to hinder prostatic growth, shrink prostate volumes, and improve BPH-related LUTS. 5ARIs are particularly beneficial for patients with larger prostates (>30-40ml). Generally the side effects of 5ARI treatment are mild, and according to the FORTA classification 5ARIs are suitable for frail elderly. 5ARI / alpha-blocker (AB) combination therapy showed the best symptomatic outcome and risk reduction for clinical progression. Combining Phosphodieseterase type 5 inhbibitors (PDE5Is) with 5ARIs counteracts the negative androgenic sexual side effects of 5ARIs, and simultaneously combines their synergistic effects on LUTS. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. A review of sorbent materials for fixed bed alkali getter systems in biomass gasifier combined cycle power generation applications

    Energy Technology Data Exchange (ETDEWEB)

    Turn, S.Q.; Kinoshita, C.M.; Ishimura, D.M.; Masutani, S.M. [Hawaii Natural Energy Inst., Honolulu, HI (United States); Zhou, J. [Hawaii Univ., Mechanical Engineering Dept., Honolulu, HI (United States)]|[Hawaii Natural Energy Inst., Honolulu, HI (United States); Hiraki, T.T. [Hawaii Univ., Biosystems Engineering Dept., Honolulu, HI (United States)

    1998-12-01

    Gas phase alkali metal compounds contribute to fouling, slagging, corrosion, and agglomeration problems in energy conversion facilities. One method of mitigation applicable at high temperature is to pass the gas stream through a fixed bed of sorbent or getter material that preferentially adsorbs alkali via physical adsorption or chemisorption. This paper reviews studies in which such materials, primarily alumina and silicate compounds, in inert and simulated combustor flue gas conditions were screened. Emathlite, diatomaceous earth, kaolinite, and activated bauxite were identified as potential sorbents and were tested thermogravimetrically or in packed beds under various process conditions. Test experience with candidate sorbent materials in an environment representative of process conditions following a hot filter in a biomass integrated gasifier combined cycle system was found to be lacking. (Author)

  20. Influence of sex hormone levels on gingival enlargement in adolescent patients undergoing fixed orthodontic therapy: A pilot study

    Directory of Open Access Journals (Sweden)

    Rajesh Hosadurga

    2016-01-01

    Full Text Available Background: Sex hormones may be a modifying factor in the periodontal disease pathogenesis. Aim: The association between gingival enlargement and sex hormone levels in adolescent patients undergoing fixed orthodontic therapy needs to be determined. Settings and Design: This study was conducted in the Department of Periodontology in association with the Department of Orthodontics, Yenepoya Dental College, Yenepoya University, Mangaluru. Materials and Methods: A pilot study was conducted on 21 adolescent patients between the age group of 13–19 years, who had undergone fixed orthodontic therapy for at least 3 months. Apicocoronally, the gingival enlargement was assessed by the index described by Miller and Damm. Miranda and Brunet index was used to assess gingival overgrowth in the buccal–lingual direction in the interdental papilla. Furthermore, the patients were assigned to two groups - Group 1-GE and Group 2-non-GE. Sex hormones assessed were estradiol and progesterone in females and testosterone in males in both groups. Results: 57.1% of the study population had enlargement of the gingiva. The mean plaque score was 0.59 and 0.56, respectively, in both groups. A statistically significant relationship was found between estradiol and testosterone levels with gingival enlargement. However, a significant relationship was not obtained for progesterone levels with the gingival enlargement. Conclusion: Direct correlation between estradiol, testosterone, and gingival enlargement was seen.

  1. Twice-daily brinzolamide/brimonidine fixed combination versus brinzolamide or brimonidine in open-angle glaucoma or ocular hypertension.

    Science.gov (United States)

    Aung, Tin; Laganovska, Guna; Hernandez Paredes, Tania Josefina; Branch, James D; Tsorbatzoglou, Alexis; Goldberg, Ivan

    2014-12-01

    To compare the intraocular pressure (IOP)-lowering efficacy and safety of brinzolamide 1% and brimonidine 0.2% fixed combination (BBFC) with that of brinzolamide 1% or brimonidine 0.2% monotherapy, all dosed 2 times per day (BID). Six-month, phase 3, randomized, multicenter, double-masked clinical trial. A total of 560 patients with primary open-angle glaucoma or ocular hypertension who had insufficient IOP reduction with their current therapeutic regimen or who were receiving ≥ 2 IOP-lowering medications. Patients received BBFC (n = 193), brinzolamide 1% (n = 192), or brimonidine 0.2% (n = 175) BID. The primary end point was mean change in diurnal IOP from baseline to month 3. Supportive end points included mean diurnal IOP change from baseline at week 2, week 6, and month 6; and mean IOP, mean IOP change from baseline, mean percentage IOP change from baseline, and percentage of patients with IOP brimonidine, 26.0 ± 0.19 mmHg). At month 3, BBFC lowered mean diurnal IOP from baseline to a significantly greater extent than brinzolamide (least squares [LS] mean difference: -1.4 mmHg; P brimonidine (LS mean difference: -1.5 mmHg; P brimonidine. The most common adverse drug reactions were ocular side effects, including hyperemia, blurred vision, allergic-type reactions, and discomfort. The incidence of hyperemia of the eye was slightly lower with brinzolamide than with BBFC and brimonidine, whereas blurred vision and ocular discomfort were slightly more common with BBFC than with brinzolamide or brimonidine. Brinzolamide 1% and brimonidine 0.2% fixed combination administered BID had a significantly greater IOP-lowering effect than either brinzolamide or brimonidine alone and displayed a safety profile consistent with its individual components. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  2. 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

  3. Efficacy and tolerability of fixed-dose combination of perindopril/indapamide in type 2 diabetes mellitus: PICASSO trial.

    Science.gov (United States)

    Farsang, Csaba

    2014-03-01

    Hypertension and type 2 diabetes mellitus (T2DM) synergistically deteriorate the vascular environment, making blood pressure reduction challenging, and substantially increasing cardiovascular risk. In the real-life, open-label, observational, PICASSO study, 9,257 hypertensive patients unsuccessfully treated with antihypertensives were switched to fixed-dose combination of perindopril 10 mg/indapamide 2.5 mg. In this subgroup analysis, we analyzed changes in blood pressure and laboratory parameters of 2,762 hypertensive patients with T2DM or pre-diabetes. After 3 months of treatment, significant decreases in office blood pressure were noted in the whole cohort (-27.0±14.8/-12.7±9.8 mmHg; p<0.001). Significant decreases were also recorded in patients with grade 1 hypertension (19.2±10.0/-9.4±7.9 mmHg), grade 2 (29.2±10.9/-13.3±8.7 mmHg) and grade 3 (-45.1±15.4/-21.5±11.2 mmHg). Significant decreases in ambulatory blood pressure were also noted (n=93). In patients previously treated with angiotensin-converting enzyme inhibitor±hydrochlorothiazide or angiotensin receptor blocker±hydrochlorothiazide, mean 24-h blood pressure decreased by 23.4±13.9/11.5±9.7 and 22.3±8.7/10.4±13.2 mmHg, respectively (p<0.001). Treatment was well tolerated and the switch to treatment with perindopril/indapamide was associated with improvements in laboratory parameters. Data from this diabetes subgroup analysis suggest that fixed combination of perindopril 10 mg/indapamide 2.5 mg should be routinely considered for the treatment of hypertension in diabetic patients who are unsuccessfully managed with other antihypertensive medications.

  4. Non-scaling fixed field alternating gradient permanent magnet cancer therapy accelerator

    Science.gov (United States)

    Trbojevic, Dejan

    2017-05-23

    A non-scaling fixed field alternating gradient accelerator includes a racetrack shape including a first straight section connected to a first arc section, the first arc section connected to a second straight section, the second straight section connected to a second arc section, and the second arc section connected to the first straight section; an matching cells configured to match particle orbits between the first straight section, the first arc section, the second straight section, and the second arc section. The accelerator includes the matching cells and an associated matching procedure enabling the particle orbits at varying energies between an arc section and a straight section in the racetrack shape.

  5. Adherence to a fixed-dose combination of rosiglitazone maleate/metformin hydrochloride in subjects with type 2 diabetes mellitus: a retrospective database analysis.

    Science.gov (United States)

    Vanderpoel, Daniel R; Hussein, Mohamed A; Watson-Heidari, Teresa; Perry, Andrew

    2004-12-01

    In 2002, fixed-dose combination therapy (FDCT) with rosiglitazone maleate plus metformin hydrochloride became available for the treatment of type 2 diabetes mellitus (DM-2) in subjects whose disease was uncontrolled on monotherapy with metformin or a thiazolidinedione. FDCT allows a reduced pill burden and a less complex medication regimen. The objective of this study was to assess changes in medication adherence rates associated with oral hypoglycemic agents in subjects switching from either monotherapy or dual therapy with metformin and/or rosiglitazone to rosiglitazone-metformin FDCT. In this retrospective database analysis, data were obtained from the pharmacy claims database of a large health benefits company. Prescription claims for subjects aged > or =18 years with DM-2 whose disease was uncontrolled on monotherapy with metformin or a thiazolidinedione were analyzed over a 12-month study period (a 6-month preindex period and a 6-month postindex period). Some subjects were receiving monotherapy with either metformin or rosiglitazone during the preindex period and remained on monotherapy throughout the postindex period (Mono/Mono cohort), switched to dual therapy with both agents (Mono/Dual cohort), or switched to FDCT (Mono/FDCT cohort). Some subjects were receiving dual therapy with metformin and rosiglitazone during the preindex period and remained on dual therapy throughout the postindex period (Dual/Dual cohort) or switched to FDCT (Dual/FDCT cohort). A medication possession ratio (MPR)-a proxy measurement of medication adherence-was calculated for each subject for each period. Changes in medication adherence were compared using a general linear model. Overall, data from the records of 16,928 subjects (8499 men, 8429 women; mean [SD] age, 58.12 [11.97] years) were included in this study. There was significantly less reduction in the MPR change for the Mono/FDCT cohort compared with the Mono/Dual cohort (-4.6% vs -12.4%; P FDCT cohort compared with the

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

    Directory of Open Access Journals (Sweden)

    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

  7. Cancer nanomedicine: from targeted delivery to combination therapy.

    Science.gov (United States)

    Xu, Xiaoyang; Ho, William; Zhang, Xueqing; Bertrand, Nicolas; Farokhzad, Omid

    2015-04-01

    The advent of nanomedicine marks an unparalleled opportunity to advance the treatment of various diseases, including cancer. The unique properties of nanoparticles (NPs), such as large surface-to-volume ratio, small size, the ability to encapsulate various drugs, and tunable surface chemistry, give them many advantages over their bulk counterparts. This includes multivalent surface modification with targeting ligands, efficient navigation of the complex in vivo environment, increased intracellular trafficking, and sustained release of drug payload. These advantages make NPs a mode of treatment potentially superior to conventional cancer therapies. This review highlights the most recent developments in cancer treatment using NPs as drug delivery vehicles, including promising opportunities in targeted and combination therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Combination of photodynamic therapy and immunotherapy - evolving role in dermatology

    Science.gov (United States)

    Wang, Xiu-Li; Wang, Hong-Wei; Huang, Zheng

    2008-02-01

    Photodynamic therapy (PDT) is a promising treatment modality. It offers alternative options in the treatment of cancer and vascular diseases. In cancer treatment, PDT has been used primarily for localized superficial or endoluminal malignant and premalignant conditions. More recently, its application has also been expanded to solid tumors. However, its antitumor efficacy remains debatable and its acceptance still variable. Pre-clinical studies demonstrate that, in addition to the primary local cytotoxicity, PDT might induce secondary host immune responses, which may further enhance PDT's therapeutic effects on primary tumor as well as metastasis. Therefore, PDT-induced local and systemic antitumor immune response might play an important role in successful control of malignant diseases. Furthermore, PDT's antitumor efficacy might also be enhanced through an effective immunoadjuvant or immunomodulator. Our recent clinical data also indicate that improved clinical outcomes can be obtained by a combination of PDT and immunomodulation therapy for the treatment of pre-malignant skin diseases. For instance, the combination of topical ALA-PDT and Imiquimod is effective for the treatment of genital bowenoid papulosis. This presentation will also report our preliminary data in developing combination approaches of PDT and immunotherapy for actinic keratosis (AK), basal cell carcinomas (BCCs) and Bowen's disease.

  9. Combined aquaretic and diuretic therapy in acute heart failure

    Directory of Open Access Journals (Sweden)

    Goyfman M

    2017-06-01

    Full Text Available Michael Goyfman,1 Paul Zamudio,2 Kristine Jang,3 Jennifer Chee,3 Catherine Miranda,2 Javed Butler,1 Nand K Wadhwa2 1Division of Cardiology, 2Division of Nephrology, 3Department of Medicine, Stony Brook School of Medicine, Stony Brook, NY, USA Introduction: Acute heart failure (AHF is a leading cause of hospitalization and readmission in the US. The present study evaluated maximum diuresis while minimizing electrolyte imbalances, hemodynamic instability, and kidney dysfunction, to achieve a euvolemic state safely in a shorter period of time.Methods and results: A protocol of combined therapy with furosemide, metolazone, and spironolactone, with or without tolvaptan and acetazolamide, was used in 17 hospitalized patients with AHF. The mean number of days on combination diuretic protocol was 3.8 days. The mean daily fluid balance was 3.0±2.1 L negative. The mean daily urine output (UOP was 4.1±2.0 L (range 1.8–10.5 L. There were minimal fluctuations in serum electrolyte levels and serum creatinine over the duration of diuretic therapy. There was no statistically significant change in patients’ creatinine from immediately prior to therapy to the last day of therapy, with a mean increase in creatinine of 0.14 mg/dL (95% CI −0.03, +0.30, p=0.10.Conclusion: Our strategy of treating AHF by achieving high UOP, while maintaining stable electrolytes and creatinine in a short period to euvolemic state, is safe. Keywords: diuretics, aquaretic, acute heart failure, volume overload

  10. Evaluation of fixed dose combination of glimepiride and metformin in patients with type 2 diabetes. Results of Russian observational study

    Directory of Open Access Journals (Sweden)

    Natalya Vladislavovna Zaytseva

    2015-04-01

    Full Text Available Aim.To investigate the efficacy and safety of combined glimepiride and metformin therapy in patients with type 2 diabetes mellitus (T2DM.Materials and methods.A multi-centre, open-label, prospective, observational study was conducted. A total of 1200 patients with T2DM inadequately controlled with metformin, glimepiride or combination of metformin + glimepiride were enrolled. Change in serum glycated haemoglobin (HbA1c, fasting plasma glucose (FPG, and postprandial blood glucose (PPG levels; weight; waist circumference and hypoglycemic episodes were evaluated.Results.Baseline HbA1c levels (8.24% ± 0.42% were significantly reduced after 12 weeks of treatment (7.48% ± 0.48% and at the end of the study(6.88% ± 0.56%. Target HbA1c levels (≤7% were achieved in 65.1% of patients at the final visit at 24 weeks. FPG and PPG levels decreased by 1.45 ± 1.14 mmol/l and 2.17 ± 1.27 mmol/l respectively (p < 0.001. No severe hypoglycemic events were reported. Body mass index reduced by 0.85 ± 1.28 kg/m2 (p < 0.001.Conclusion. Combined glimepiride and metformin therapy significantly improved long-term glycemic control in patients with T2DM during the period of 24 weeks without additional risk of hypoglycemic events or weight gain.

  11. 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 (FEV 1 ) value at baseline and the post-improvement FEV 1 value. Changes in FEV 1 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.

  12. "Liquid morphology": Immunochemical analysis of proteins extracted from formalin-fixed paraffin-embedded tissues: Combining proteomics with immunohistochemistry.

    Science.gov (United States)

    Becker, Karl-Friedrich; Taylor, Clive R

    2011-01-01

    Currently there are extensive efforts, national and international, to define the parameters affecting biomarker expression and stability to integrate this knowledge into diagnostic and therapeutic decisions, in effect to determine accurately and reliably which patients are likely to benefit from new targeted therapies, and which patients will not. Although challenging, efforts are being made to improve standardization of the preanalytical phase in hospitals. The introduction of guidelines for fixation and sample processing may improve molecular characterization of tissues to some degree. However, the authors believe that these approaches are likely to fall short because of the complexity of the problem, the diversity of personnel and institutions involved, and formidable issues of logistics and expense on a national or worldwide basis. Therefore, an alternative approach is proposed, specifically that the identification of biomarkers (quantifiable internal reference standards) that serve as indicators of tissue quality for both immunohistochemistry and protein microarrays, will improve the quality and reproducibility of in-vitro molecular diagnostic tests, and further may serve as a basis for precise quantification of analytes (proteins) in formalin-fixed paraffin-embedded tissues. Successful development and application of this approach would assure that protein biomarker profiles determined by proteomics or immunohistochemistry are related to the disease of the patient and not to vagaries of tissue processing.

  13. Safety and efficacy of once daily ledipasvir/sofosbuvir fixed-dose combination in patients with chronic hepatitis C.

    Science.gov (United States)

    Gamal, N; Andreone, P

    2016-01-01

    During the past couple of years, the regulatory authorities have approved seven new direct-acting antivirals (DAAs) for the treatment of chronic hepatitis C (CHC). In 2014, the US FDA approved the fixed dose combination of ledipasvir (LDV) plus sofosbuvir (SOF) for the treatment of genotype (GT) 1 HCV and the European Commission Granted its marketing authorization to treat patients with GT1 and 4. This regimen showed outstanding rates of virologic response along with a favorable safety profile with a very low rate of both virologic failure and treatment discontinuation. In this review, we sought to review the pharmacokinetics, clinical efficacy and safety profile pertaining to LDV/SOF combination in treatment of CHC with special emphasis on phase III clinical trials. In all phase III trials, the 12-week course of this new interferon (IFN)-sparing regimen has delivered high virologic cure rates among patient with GT1 and 4 both treatment-naïve and - experienced Data about its effectiveness in patients under 18 years of age, end-stage renal disease and patients with significant other organ involvement are eagerly awaited.

  14. Transient Serotonin Toxicity Evoked by Combination of Electroconvulsive Therapy and Fluoxetine

    Directory of Open Access Journals (Sweden)

    René Klysner

    2014-01-01

    Full Text Available The serotonin syndrome has been described only in rare instances for electroconvulsive therapy combined with an antidepressant medication. We describe a case of serotonin toxicity induced by electroconvulsive therapy in combination with fluoxetine.

  15. Relative efficacy of psychotherapy and combined therapy in the treatment of depression: A meta-analysis.

    NARCIS (Netherlands)

    Maat, S.M.; Dekker, J.J.M.; Schoevers, R.A.; Jonghe, de F.

    2007-01-01

    0.001). Conclusions In the acute treatment of adult psychiatric outpatients with major depressive disorder, patient compliance with combined therapy matches compliance with psychotherapy alone. Combined therapy is more efficacious than psychotherapy alone. However, these results depend on severity

  16. Adapalene-benzoyl peroxide, a unique fixed-dose combination topical gel for the treatment of acne vulgaris: a transatlantic, randomized, double-blind, controlled study in 1670 patients.

    Science.gov (United States)

    Gollnick, H P M; Draelos, Z; Glenn, M J; Rosoph, L A; Kaszuba, A; Cornelison, R; Gore, B; Liu, Y; Graeber, M

    2009-11-01

    Combination therapy utilizing agents with complementary mechanisms of action is recommended by acne guidelines to help simultaneously target multiple pathogenic factors. A unique, topical, fixed-dose combination gel with adapalene 0.1% and benzoyl peroxide (BPO) 2.5% has recently been developed for the once-daily treatment of acne. To evaluate the efficacy and safety of adapalene 0.1%-BPO 2.5% fixed-dose combination gel (adapalene-BPO) relative to adapalene 0.1% monotherapy (adapalene), BPO 2.5% monotherapy (BPO), and the gel vehicle (vehicle) in a large population for the treatment of acne vulgaris. In total, 1670 subjects were randomized in a double-blind controlled trial to receive adapalene-BPO, adapalene, BPO or vehicle for 12 weeks (1 : 1 : 1 : 1 randomization). Evaluations included success rate (subjects 'clear' or 'almost clear'), percentage change in lesion count from baseline, cutaneous tolerability and adverse events. Adapalene-BPO was significantly more effective than corresponding monotherapies, with significant differences in percentage lesion count change observed as early as 1 week. Cutaneous tolerability profile was similar to adapalene. Adverse events were more frequent with the combination therapy (mainly due to an increase in mild-to-moderate dry skin), occurred early in the study, and were transient. Adapalene-BPO provides significantly greater and synergistic efficacy and a faster onset of action with an acceptable safety profile in the treatment of acne vulgaris when compared with the corresponding vehicle and the adapalene and BPO monotherapies.

  17. Transient Serotonin Toxicity Evoked by Combination of Electroconvulsive Therapy and Fluoxetine

    DEFF Research Database (Denmark)

    Klysner, René; Bjerg Bendsen, Birgitte; Hansen, Maja Soon

    2014-01-01

    The serotonin syndrome has been described only in rare instances for electroconvulsive therapy combined with an antidepressant medication. We describe a case of serotonin toxicity induced by electroconvulsive therapy in combination with fluoxetine.......The serotonin syndrome has been described only in rare instances for electroconvulsive therapy combined with an antidepressant medication. We describe a case of serotonin toxicity induced by electroconvulsive therapy in combination with fluoxetine....

  18. Combined preoperative therapy for oral cancer with nedaplatin and radiation

    Energy Technology Data Exchange (ETDEWEB)

    Adachi, Masatoshi; Shibata, Akihiko; Hayashi, Munehiro [Nippon Dental Univ., Tokyo (Japan). Hospital] (and others)

    2002-03-01

    We performed preoperative combined therapy using nedaplatin (CDGP) and radiation in 12 patients with squamous cell carcinoma originating from the oral cavity and maxillary sinus, and examined for any adverse events that may have occurred during this therapeutic regimen. Regarding the irradiation, external irradiation utilizing a 6 MV linac (linear accelerator) at a dose of 2.0 Gy/day was performed 5 times a week, with the target total radiation dose set at 40 Gy. In addition, CDGP was intravenously administered 30 minutes before irradiation at a dose of 5 mg/m{sup 2}/day. Mucositis was observed in all 12 subjects, however, the severity was observed to be grade 1-2 with no major differences in comparison to the patients given standard radiation monotherapy. Two subjects developed grade 3 leucopenia and were thus given granulocyte colony stimulating factor (G-CSF). In addition, grade 2 and grade 3 thrombocytopenia were both observed in one subject each. The subject with grade 3 thrombocytopenia required a platelet transfusion during surgery. No marked changes in serum creatinine levels were noted. These findings are therefore considered to provide evidence supporting the safety of this combination therapy. (author)

  19. Pyronaridine-artesunate combination therapy for the treatment of malaria.

    Science.gov (United States)

    Kurth, Florian; Bélard, Sabine; Basra, Arti; Ramharter, Michael

    2011-12-01

    Pyronaridine-artesunate is among the most promising novel artemisinin combination therapies for the treatment of malaria. A series of clinical phase II and III trials have been conducted for the indications of uncomplicated falciparum and vivax malaria in Africa and Asia. On the basis of these novel data, this review aims to provide an appraisal of current evidence and a perspective for its future role in the antimalarial portfolio. Pyronaridine-artesunate demonstrated repeatedly high efficacy in the treatment of vivax and falciparum malaria and noninferiority was established compared to standard comparator regimens. An innovative paediatric drug formulation was developed in parallel to the tablet formulation for the treatment of young children. Pharmacokinetic analysis showed dose linearity, low interindividual variation and absence of a clinically important effect of food on the bioavailability of this drug combination. Overall tolerability and safety data are reassuring; however, further surveillance of safety in special patient populations including young children is warranted. Pyronaridine-artesunate - currently under evaluation by the European Medicines Agency - may become a preferred choice as first-line therapy in malaria endemic regions based on its low cost, long shelf-life, simplified once-daily dosing regimen, proven efficacy against falciparum and vivax malaria, and the parallel clinical development of a paediatric drug formulation.

  20. Survival Outcomes for Combined Modality Therapy for Sinonasal Undifferentiated Carcinoma.

    Science.gov (United States)

    Kuo, Phoebe; Manes, R Peter; Schwam, Zachary G; Judson, Benjamin L

    2017-01-01

    Objective Sinonasal undifferentiated carcinoma is a rare and aggressive malignancy of the nasal cavity and paranasal sinuses. Multi-institutional studies examining outcomes of combined modality treatment versus other treatment modalities have not been performed. The objective of our study was to present outcomes for multimodality therapy through use of the National Cancer Database. Study Design Retrospective cohort study. Setting National Cancer Database. Methods A total of 435 cases of SNUC diagnosed between 2004 and 2012 were identified. Kaplan-Meier analyses were performed to find 5-year cumulative survival rates. Multivariate Cox regression evaluated overall survival based on treatment when adjusting for other prognostic factors (age, primary site, sex, race, comorbidity, insurance, and TNM stage). Within the surgery + chemoradiotherapy group, survival analysis was also performed to compare outcomes for induction and adjuvant chemotherapy. Results The cumulative 5-year survival rate was 41.5%, and 36.1% of patients received surgery with chemoradiotherapy. In multivariate analysis, surgery + chemoradiotherapy was associated with significantly improved overall survival versus surgery + radiotherapy and radiotherapy but not significantly different from chemoradiotherapy. Within the surgery + chemoradiotherapy group, induction and adjuvant chemotherapy groups did not have associated differences in survival. Conclusion Combined modality therapy (chemoradiotherapy or surgery + chemoradiotherapy) is associated with improved survival outcomes versus other treatment modalities in patients with sinonasal undifferentiated carcinoma.

  1. Improved outcome in solitary bone plasmacytomata with combined therapy.

    Science.gov (United States)

    Avilés, A; Huerta-Guzmán, J; Delgado, S; Fernández, A; Díaz-Maqueo, J C

    1996-09-01

    Solitary bone plasmacytoma (SBP) is a rare presentation of plasma cell dyscrasias. Radiotherapy has been considered the treatment of choice, however, most patients will develop multiple myeloma, 3 to 10 years after initial diagnosis and treatment. No innovations have been introduced in the treatment of SBP in the last 30 years. We began a prospective clinical trial to assess the efficacy and toxicity of adjuvant chemotherapy with low doses of melphalan and prednisone administered to patients with SBP after radiation therapy in an attempt to improve the disease-free survival and overall survival. Between 1982 and 1989, 53 patients with SBP were randomly assigned to be treated with either local radiotherapy with doses ranged from 4000 to 5000 cGy to achieve local control of disease (28 patients) or the same radiotherapy schedule followed by melphalan and prednisone given every 6 weeks for 3 years (25 patients). After a median follow-up of 8.9 years, disease-free survival and overall survival were improved in patients who were treated with combined therapy, 22 patients remain alive and free of disease in the combined treatment group compared to only 13 patients in the radiotherapy group (p radiotherapy in patients with SBP improved duration of remission and survival without severe side-effects. However, as with other studies in SBP, the group was too small to draw definitive conclusions and more controlled clinical trials are necessary to define the role of this therapeutic approach in patients with SBP.

  2. Rapid Screening of Novel Agents for Combination Therapy in Sarcomas

    Directory of Open Access Journals (Sweden)

    Christopher L. Cubitt

    2013-01-01

    Full Text Available For patients with sarcoma, metastatic disease remains very difficult to cure, and outcomes remain less than optimal. Treatment options have not largely changed, although some promising gains have been made with single agents in specific subtypes with the use of targeted agents. Here, we developed a system to investigate synergy of combinations of targeted and cytotoxic agents in a panel of sarcoma cell lines. Agents were investigated alone and in combination with varying dose ratios. Dose-response curves were analyzed for synergy using methods derived from Chou and Talalay (1984. A promising combination, dasatinib and triciribine, was explored in a murine model using the A673 cell line, and tumors were evaluated by MRI and histology for therapy effect. We found that histone deacetylase inhibitors were synergistic with etoposide, dasatinib, and Akt inhibitors across cell lines. Sorafenib and topotecan demonstrated a mixed response. Our systematic drug screening method allowed us to screen a large number of combinations of sarcoma agents. This method can be easily modified to accommodate other cell line models, and confirmatory assays, such as animal experiments, can provide excellent preclinical data to inform clinical trials for these rare malignancies.

  3. Pancreatic cancer: systemic combination therapies for a heterogeneous disease.

    Science.gov (United States)

    Melisi, Davide; Calvetti, Lorenzo; Frizziero, Melissa; Tortora, Giampaolo

    2014-01-01

    Pancreatic cancer is the only human malignancy for which patients' survival has not improved substantially during the past 30 years. Despite advances in the comprehension of the molecular mechanisms underlying pancreatic carcinogenesis, current systemic treatments offer only a modest benefit in tumor-related symptoms and survival. Over the past decades, gemcitabine and its combination with other standard cytotoxic agents have been the reference treatments for advanced pancreatic cancer patients. The recent introduction of the three-drug combination regimen FOLFIRINOX or the new taxane nab-paclitaxel represent key advances for a better control of the disease. Novel agents targeting molecular mechanisms involved in cancer development and maintenance are currently under clinical investigation. This review describes the most important findings in the field of systemic combination therapies for the treatment of pancreatic cancer. We discuss the emerging evidences for the clinical activity of combination treatments with standard chemotherapy plus novel agents targeting tumor cell-autonomous and tumor microenvironment signaling pathways. We present some of the most important advances in the comprehension of the molecular mechanisms responsible for the chemoresistance of pancreatic cancer and the emerging therapeutic targets to overcome this resistance.

  4. Fixed-Combination Gels of Adapalene and Benzoyl Peroxide Provide Optimal Percutaneous Absorption Compared to Monad Formulations of These Compounds: Results from Two In Vitro Studies.

    Science.gov (United States)

    Osman-Ponchet, Hanan; Sevin, Karine; Gaborit, Alexandre; Wagner, Nathalie; Poncet, Michel

    2017-03-01

    Adapalene 0.1%/benzoyl peroxide 2.5% (0.1% A/BPO) and adapalene 0.3%/BPO 2.5% (0.3% A/BPO) gels are fixed-combination options for the topical treatment of acne. However, the active compounds of these combinations are also available as monads, to be used in association or as monotherapy. These two in vitro studies determined the effect of different treatment regimens on the percutaneous absorption of adapalene (0.1% and 0.3%) gels and BPO 2.5% gel in ex vivo human skin. In vitro percutaneous absorption studies were conducted using full-thickness human skin from six donors. Treatment regimens included the application of 0.1% A/BPO, 0.3% A/BPO, or four free-combination regimens of the monads. Skin samples were incubated for 24 h. Concentrations of adapalene and BPO equivalent (BPO-eq) (i.e. benzoic acid after chemical transformation of BPO) were measured using high-performance liquid chromatography. Comparison of regimens was performed using a bioequivalence criterion (estimated ratio bewteen 0.8 and 1.25). The fixed combination 0.3% A/BPO regimen demonstrated more than three times higher absorption of adapalene versus the fixed-combination 0.1% A/BPO. Based on the bioequivalence acceptance criterion, all four free-combination regimens were different from 0.1% A/BPO and 0.3% A/BPO, with higher adapalene release delivered by the fixed combinations versus the free combinations. For BPO-eq, the results showed that the free-combination regimens where adapalene 0.1% was applied first were different from 0.1% A/BPO, with lower BPO-eq release delivered by these regimens compared to the fixed combination. The regimen adapalene 0.3% for 10 h followed by BPO 2.5% delivered lower BPO-eq release compared to the fixed combination. The fixed-combination A/BPO gels provide optimal percutaneous absorption of the active compounds compared to free combinations of adapalene 0.1%, adapalene 0.3%, and BPO 2.5%. The higher concentration of adapalene in the 0.3% A/BPO gel and the

  5. Atypical and Typical Winter Depressive Symptoms and Responsiveness to Light Therapy, Cognitive-Behavioral Therapy, or Combination Treatment

    National Research Council Canada - National Science Library

    Johnson, Leigh G; Rohan, Kelly J

    2005-01-01

    ...), group cognitive-behavioral therapy (CBT), or combination therapy (CBT+LT). Atypical and typical symptoms were assessed using subscales of the Structured Interview Guide for the Hamilton Rating Scale for Depression - SAD Version (SIGH-SAD...

  6. Treatment timing of MARA and fixed appliance therapy of Class II malocclusion.

    Science.gov (United States)

    Ghislanzoni, Luis Tomas Huanca; Baccetti, Tiziano; Toll, Douglas; Defraia, Efisio; McNamara, James A; Franchi, Lorenzo

    2013-06-01

    The objective of this study is to evaluate the effect of timing on Mandibular Anterior Repositioning Appliance (MARA) and fixed appliance treatment of Class II malocclusion in a prospective clinical trial. The treated sample consisted of 51 consecutively treated patients at prepubertal (n = 21), pubertal (n = 15), and postpubertal (n = 15) stages of development. Control groups for the three treated groups were generated from growth data of untreated Class II subjects. Lateral cephalograms were digitized and superimposed via cephalometric software at T1 (pre-treatment) and T2 (after comprehensive treatment). The T1-T2 changes in the treated groups were compared to those in their corresponding control groups with Mann-Whitney tests with Bonferroni correction. Mandibular elongation was greater at the pubertal stage (Co-Gn +2.6 mm, with respect to controls). Headgear effect on the maxilla was greater in the pre-peak sample (Co-A -1.9 mm, with respect to controls). Dentoalveolar compensations (proclination of lower incisors, extrusion and mesialization of lower molars, and reduction in the overbite) were significant in the pre-peak and post-peak groups. Optimal timing for Class II treatment with MARA appliance is at the pubertal growth spurt, with enhanced mandibular skeletal changes and minimal dentoalveolar compensations.

  7. Long-term stability of lip bumper therapy followed by fixed appliances.

    Science.gov (United States)

    Solomon, Michael Joseph; English, Jeryl D; Magness, W Bonham; McKee, Chris John

    2006-01-01

    Lip bumper treatment has been shown to successfully increase arch width, procline the incisors, and distalize molars. However, few studies have been performed showing the long-term stability of lip bumper treatment. In this study, mandibular casts taken by a single practitioner from 51 patients treated with lip bumpers without rapid palatal expansion were analyzed at pretreatment, post-lip bumper treatment, posttreatment, and long-term out of treatment. Measurements of arch width, arch depth, arch length, and anterior crowding were made. During treatment, there was a mean decrease in irregularity of 3.73 mm, with a posttreatment increase of 0.76 mm, for a net decrease of 2.97 mm. Despite posttreatment decreases, significant gains in arch width were maintained for extended periods of time. The intercanine width had a net increase of 1.78 mm (19% relapse), first premolars 3.39 mm (26% relapse), second premolars 2.58 mm (34% relapse), and first molars 2.17 mm (20% relapse). Lip bumper treatment along with fixed appliances is an effective means to obtain long-term increases in arch width and decreases in the irregularity index.

  8. Ledipasvir/sofosbuvir fixed-dose combination tablet in Taiwanese patients with chronic genotype 1 hepatitis C virus.

    Science.gov (United States)

    Chuang, Wan-Long; Chien, Rong-Nan; Peng, Cheng-Yuan; Chang, Ting-Tsung; Lo, Gin-Ho; Sheen, I-Shyan; Wang, Horng-Yuan; Chen, Jyh-Jou; Yang, Jenny C; Knox, Steven J; Gao, Bing; Garrison, Kimberly L; Mo, Hongmei; Pang, Phillip S; Hsu, Yu-Chun; Hu, Tsung-Hui; Chu, Chi-Jen; Kao, Jia-Horng

    2016-07-01

    Pegylated-interferon-alpha plus ribavirin is the current standard-of-care regimen for treating chronic hepatitis C virus (HCV) infection in Taiwan; however, interferon-based regimens can be poorly tolerated. The interferon-free, two-drug, fixed-dose combination tablet ledipasvir/sofosbuvir is approved in Europe, the USA, and Japan for treating chronic genotype 1 HCV infection. Little is known about its efficacy/safety in Taiwanese patients. In this multicenter, open-label, phase 3b (NCT02021656) study, 85 Taiwanese patients (n = 42, treatment-naïve; n = 43, treatment-experienced) with chronic genotype 1 HCV infection (±compensated cirrhosis) received 12 weeks of ledipasvir/sofosbuvir fixed-dose combination tablet. The primary efficacy end point was the proportion of patients with sustained virologic response 12 weeks after treatment discontinuation (SVR12). Safety and pharmacokinetic data were collected. The overall SVR12 rate was 98% (83/85), with 100% (42/42) and 95% (41/43) of treatment-naïve and treatment-experienced patients, respectively, achieving SVR12. There were no on-treatment virologic failures. One patient relapsed after treatment discontinuation; one patient withdrew consent on day 2. The most common treatment-emergent adverse event (AE) was headache (14%, 12/85). There was one grade 3 AE (small cell lung cancer unrelated to ledipasvir/sofosbuvir), no grade 4 AEs, and four grade 3-4 laboratory abnormalities. Only the patient with small cell lung cancer prematurely discontinued treatment. Two patients reported three serious AEs; none was considered related to ledipasvir/sofosbuvir. Data from this phase 3b study suggest that 12 weeks of once-daily treatment with the interferon-free, ribavirin-free regimen ledipasvir/sofosbuvir is effective and well-tolerated in Taiwanese patients with chronic genotype 1 HCV infection, irrespective of treatment history. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons

  9. Relative bioavailability and bioequivalence of a newly developed fixed combination sachet of acetylsalicylic acid and pseudoephedrine compared with a preliminary combination.

    Science.gov (United States)

    Lücker, P W; Birkel, M; Hey, B; Loose, I; Schaefer, A

    2003-10-01

    Acetylsalicylic acid (ASA) and pseudoephedrine (PSE) are often administered together for the treatment of symptoms of the common cold, i.e., nasal congestion, runny nose, sore throat and headache. Based on this fact we developed a fixed combination of 500 mg ASA and 30 mg PSE, the recommended doses for both drugs for treating symptoms of the common cold, as granulate to be dissolved in water for administration. The purpose of this open, randomized, three-factorial (three-treatment, three-period, six-sequence) Latin Square clinical study was to investigate the relative bioavailability of ASA and PSE as well as the establishment of bioequivalence after single administration of the fixed combination (final formulation for approval) of 500 mg ASA/30 mg PSE*HCl and the preliminary formulation of this combination. Pharmacokinetic characteristics AUC(norm) and C(max,norm) of ASA, its metabolite SA, and PSE, were determined as measure of rate and extent of absorption of the two formulations. The treatment ratios final/preliminary formulation and their corresponding 90% confidence intervals were calculated to establish bioequivalence. Additionally, descriptive statistics were calculated for the parameters t(max), t((1/2)), and mean residence time (MRT). In total, data from 18 healthy male volunteers were included in the pharmacokinetic evaluation. The primary target parameters were analyzed using an analysis of variance (ANOVA) after logarithmic transformation of the data. Confidence intervals of 90% were calculated for the geometric means of ratios using the mean square error term of the ANOVA. Bioequivalence criteria were fulfilled for AUC(norm) and C(max,norm). Geometric means of individual ratios of AUC(norm) and of C(max,norm) showed equal bioavailability of the new formulation compared with the preliminary. Furthermore, a relative bioavailability of approximately 100% of the preliminary formulation was shown for the newly developed formulation for all parameters. The

  10. Health outcome and safety assessment of a fixed dose combination of Amantadine, Paracetamol, Chlorpheniramine maleate, and Phenylephrine introduction in India: A prescription event monitoring study.

    Science.gov (United States)

    Krishnaprasad, K; Manshani, P; Karankumar, J

    2012-04-01

    To assess the likely impact of a fixed dose combination (FDC) of Amantadine, Paracetamol, Chlorpheniramine maleate, and Phenylephrine on the health outcome and safety profile arising from the complementary action of amantadine and other ingredients, we conducted a Prescription Event Monitoring study for patients with suspected Influenza symptoms who were prescribed this FDC in 'real life clinical settings' or clinical practice. Between August 2010 and March 2011, Questionnaires were sent to doctors who provided data on the health outcome or safety profile. Sedation and allergy, including rash, were noted in few of the patients. None of the patients reported any major events. Most of the patients (60%) were initiated on FDC therapy within the first 24 hours of symptom onset. Even as a significant proportion of the patients (24.9%) had a concurrent history of allergy / rhinitis including asthma, few of them (4.1%) reported lack of improvement and had to be complemented with antibiotics. The FDC of Amantadine, Chlorpheniramine, Paracetamol, and Phenylephrine was found to be safe and well-tolerated when administered to patients within the first 24 to 48 hours of symptom onset.

  11. Health outcome and safety assessment of a fixed dose combination of Amantadine, Paracetamol, Chlorpheniramine maleate, and Phenylephrine introduction in India: A prescription event monitoring study

    Directory of Open Access Journals (Sweden)

    K Krishnaprasad

    2012-01-01

    Full Text Available To assess the likely impact of a fixed dose combination (FDC of Amantadine, Paracetamol, Chlorpheniramine maleate, and Phenylephrine on the health outcome and safety profile arising from the complementary action of amantadine and other ingredients, we conducted a Prescription Event Monitoring study for patients with suspected Influenza symptoms who were prescribed this FDC in ′real life clinical settings′ or clinical practice. Between August 2010 and March 2011, Questionnaires were sent to doctors who provided data on the health outcome or safety profile. Sedation and allergy, including rash, were noted in few of the patients. None of the patients reported any major events. Most of the patients (60% were initiated on FDC therapy within the first 24 hours of symptom onset. Even as a significant proportion of the patients (24.9% had a concurrent history of allergy / rhinitis including asthma, few of them (4.1% reported lack of improvement and had to be complemented with antibiotics. The FDC of Amantadine, Chlorpheniramine, Paracetamol, and Phenylephrine was found to be safe and well-tolerated when administered to patients within the first 24 to 48 hours of symptom onset.

  12. Efficacy and safety of the losartan-hydrochlorothiazide combination tablet in patients with hypertension uncontrolled by angiotensin II receptor antagonist therapy: the Aichi Research on Combination therapy for Hypertension (ARCH) Study.

    Science.gov (United States)

    Maeda, Kengo; Adachi, Masayoshi; Kinoshita, Atsushi; Koh, Naoki; Miura, Yoshitaka; Murohara, Toyoaki

    2012-01-01

    The guidelines recommend combination therapy for patients who are unable to achieve target BP with monotherapy; some fixed dose therapies including an angiotensin II receptor blocker (ARB) and diuretics are available in Japan. However, to date there have been few reports on this long-term treatment and the patient profiles suited for this combination remain ambiguous. The Aichi Research on Combination therapy for Hypertension Study was a multicenter, open-label, prospective observational study that investigated the efficacy and safety of 1-year treatment with the losartan-hydrochlorothiazide (HCTZ) combination tablet in patients with hypertension uncontrolled by either ARB monotherapy or combination therapy with a calcium channel blocker (CCB). An ARB was switched to a losartan-HCTZ tablet after a pre-observation period. A total of 614 of 648 patients were evaluable (mean age, 66.3 years; 52.8% men; mean baseline blood pressure, BP, 157.7/87.9 mmHg). The BP had decreased significantly to 138.0/78.2 mmHg by month 3 (p<0.001, t-test), and 36.2% of the patients had achieved their target BP. The hypotensive effect lasted for 1 year and was found equally in the losartan-HCTZ arm and the losartan-HCTZ plus CCB arm. A stratified analysis showed significant hypotensive effects in patients with higher baseline BP, women, and patients who did not drink alcohol (p<0.001, unpaired t-test). The losartan-HCTZ combination tablet was found to have an early hypotensive effect, good tolerability, and stable long-term benefits in patients with hypertension uncontrolled by ARB monotherapy or combination therapy with a CCB.

  13. Therapeutic Cancer Vaccines in Combination with Conventional Therapy

    Directory of Open Access Journals (Sweden)

    Mads Hald Andersen

    2010-01-01

    Full Text Available The clinical efficacy of most therapeutic vaccines against cancer has not yet met its promise. Data are emerging that strongly support the notion that combining immunotherapy with conventional therapies, for example, radiation and chemotherapy may improve efficacy. In particular combination with chemotherapy may lead to improved clinical efficacy by clearing suppressor cells, reboot of the immune system, by rendering tumor cells more susceptible to immune mediated killing, or by activation of cells of the immune system. In addition, a range of tumor antigens have been characterized to allow targeting of proteins coupled to intrinsic properties of cancer cells. For example, proteins associated with drug resistance can be targeted, and form ideal target structures for use in combination with chemotherapy for killing of surviving drug resistant cancer cells. Proteins associated with the malignant phenotype can be targeted to specifically target cancer cells, but proteins targeted by immunotherapy may also simultaneously target cancer cells as well as suppressive cells in the tumor stroma.

  14. Hydrotherapy combined with Snoezelen multi-sensory therapy.

    Science.gov (United States)

    Lavie, Efrat; Shapiro, Michele; Julius, Mona

    2005-01-01

    The aim of this article is to present a new and challenging model of treatment that combines two therapeutic interventions: hydrotherapy and Snoezelen or controlled multisensory stimulation. The combination of the two therapeutic approaches enhances the treatment effect by utilizing the unique characteristics of each approach. We believe that this combined model will further enhance each media to the benefit of the clients and create a new intervention approach. This article relates to a hydrotherapy swimming pool facility that has been established at the Williams Island Therapeutic Swimming and Recreation Center, Beit Issie Shapiro, Raanana in Israel, after acquiring many years of experience and gaining substantial knowledge both in the field of hydrotherapy and Snoezelen intervention. Beit Issie Shapiro is a non-profit community organization providing a range of services for children with developmental disabilities and their families. The organization provides direct services for nearly 6,000 children and adults each year. This article provides an overview of hydrotherapy and Snoezelen and presents a case study, which will demonstrate the new model of treatment and show how this new and innovative form of therapy can be used as a successful intervention. We believe it will open a path to enriching the repertoire of therapists helping people with special needs. This article is also addressed to researchers to provide ideas for further studies in this area.

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

    Directory of Open Access Journals (Sweden)

    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.

  16. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Pharmacokinetics and safety of nifedipine GITS/candesartan fixed-dose combination in subjects with hepatic impairment
.

    Science.gov (United States)

    Liu, Yuwang; Boettcher, Michael-Friedrich; Schmidt, Anja; Unger, Sigrun; Halabi, Atef; Brendel, Erich; Blode, Hartmut

    2017-03-01

    To investigate the pharmacokinetic (PK) profiles and safety of nifedipine and candesartan after a single oral dose of nifedipine gastrointestinal therapeutic system (GITS) 30 mg/candesartan cilexetil 8 mg (N30/C8 mg) fixed-dose combination (FDC) in adults with mild to moderate hepatic impairment. A phase I, single-center, non-randomized, non-controlled, non-blinded, observational study (N = 32). PK profiles for nifedipine and candesartan were assessed in patients with mild (Child-Pugh A; group 1) or moderate (Child-Pugh B; group 2) hepatic impairment and compared with age- and gender-matched healthy controls (groups 3 and 4) following a single dose of N30/C8 FDC. Safety and tolerability were assessed throughout the study. On average, area under the plasma concentration vs. time curves (AUC) for nifedipine increased 93% and 253% in mild and moderate hepatic impairment, while maximum plasma concentrations (Cmax) increased 64% and 171%, respectively. AUC values for candesartan increased 19% and 92%, while Cmax values increased 3% and 11%, respectively. In subjects with or without liver impairment, adverse event rates were similar and consistent with the known side-effect profiles of nifedipine GITS and candesartan as monotherapies. Careful monitoring, and, if necessary, dose adjustment according to response and tolerability may be required for nifedipine GITS/candesartan FDC in patients with mild and moderate hepatic impairment.
.

  18. 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

  19. Adapalene-benzoyl peroxide once-daily, fixed-dose combination gel for the treatment of acne vulgaris: a randomized, bilateral (split-face), dose-assessment study of cutaneous tolerability in healthy participants.

    Science.gov (United States)

    Andres, Philippe; Pernin, Colette; Poncet, Michel

    2008-03-01

    Combination therapy is an effective approach to simultaneously target multiple pathogenic factors of acne. International consensus guidelines recommend the use of topical retinoids and benzoyl peroxide (BPO) for acne treatment. These drugs are often prescribed as a free combination without any safety concern associated with antibiotic use. A 3-week, randomized, controlled, investigator-blinded, single-center, bilateral (split-face), dose-assessment study was conducted comparing the cutaneous tolerability of 2 adapalene-BPO fixed-dose combination products versus various concentrations of BPO monotherapy applied once daily. Sixty healthy participants were randomized to one of the following treatment groups: adapalene 0.1%-BPO 2.5% combination product versus BPO 2.5% monotherapy; adapalene 0.1%-BPO 2.5% combination product versus BPO 5% monotherapy; adapalene 0.1%-BPO 5% combination product versus BPO 5% monotherapy; and adapalene 0.1%-BPO 5% combination product versus BPO 10% monotherapy. Assessments included total sum score (TSS) of irritation signs/ symptoms (erythema, scaling/desquamation, dryness, pruritus, stinging/burning) averaged over all postbaseline visits, individual irritation signs/symptoms (worst score), and adverse events. The overall cutaneous tolerability profile of the adapalene 0.1%-BPO 2.5% combination product was better than the combination with BPO 5% and similar to BPO 2.5% or 5% monotherapy. The combination product with BPO 5% induced significantly more irritation than BPO 5% monotherapy (P BPO 10% monotherapy (P = .001). In conclusion, the new fixed-dose adapalene 0.1%-BPO 2.5% combination product provided the best overall cutaneous tolerability profile relative to BPO monotherapy.

  20. Fixed combination of travoprost and timolol maleate reduces intraocular pressure in Japanese patients with primary open-angle glaucoma or ocular hypertension: analysis by prostaglandin analogue

    Directory of Open Access Journals (Sweden)

    Nakano T

    2016-12-01

    Hg in the bimatoprost group. Along with differences in baseline IOP between groups, an IOP-lowering effect of >1 mmHg was noted in the tafluprost, latanoprost, and travoprost groups after the switch. IOP was maintained at 13.8–14.8 mmHg throughout the follow-up period. No serious adverse events or noteworthy issues were observed in any group after the switch.Conclusion: Clinically significant IOP-reducing effects of TTFC were observed in the latanoprost, travoprost, and tafluprost groups when switching from each PGA monotherapy, while there were some differences in effects between groups, with minimal safety concerns. Keywords: adverse event intraocular pressure, prostaglandin analogue, switching therapy, travoprost/timolol fixed combination

  1. Comparison of the pharmacokinetics and tolerability of HCP1004 (a fixed-dose combination of naproxen and esomeprazole strontium) and VIMOVO® (a marketed fixed-dose combination of naproxen and esomeprazole magnesium) in healthy volunteers.

    Science.gov (United States)

    Choi, YoonJung; Han, HyeKyung; Shin, Dongseong; Lim, Kyoung Soo; Yu, Kyung-Sang

    2015-01-01

    HCP1004 is a newly developed fixed-dose combination of naproxen (500 mg) and esomeprazole strontium (20 mg) that is used in the treatment of rheumatic diseases and can reduce the risk of nonsteroidal anti-inflammatory drug-associated ulcers. The aim of this study was to evaluate the pharmacokinetics (PK) and safety of HCP1004 compared to VIMOVO(®) (a marketed fixed-dose combination of naproxen and esomeprazole magnesium). An open-label, randomized, two-treatment, two-sequence crossover, single-dose clinical study was conducted in 70 healthy volunteers. In each period, a reference (VIMOVO(®)) or test (HCP1004) drug was administered orally, and serial blood samples for PK analysis were collected up to 72 hours after dosing. To evaluate the PK profiles, the maximum plasma concentration (Cmax) and the area under the concentration-time curve from 0 to the last measurable time (AUC0-t) were estimated using a noncompartmental method. Safety profiles were evaluated throughout the study. Sixty-six of the 70 subjects completed the study. The Cmax (mean ± standard deviation) and AUC0-t (mean ± standard deviation) for naproxen in HCP1004 were 61.67 ± 15.16 µg/mL and 1,206.52 ± 166.46 h · µg/mL, respectively; in VIMOVO(®); these values were 61.85 ± 14.54 µg/mL and 1,211.44 ± 170.01 h · µg/mL, respectively. The Cmax and AUC0-t for esomeprazole in HCP1004 were 658.21 ± 510.91 ng/mL and 1,109.11 ± 1,111.59 h · ng/mL, respectively; for VIMOVO(®), these values were 595.09 ± 364.23 ng/mL and 1,015.12 ± 952.98 h · ng/mL, respectively. The geometric mean ratios and 90% confidence intervals (CIs) (HCP1004 to VIMOVO(®)) of the Cmax and AUC0-t of naproxen were 0.99 (0.94-1.06) and 1.00 (0.98-1.01), respectively. For esomeprazole, the geometric mean ratios (90% CI) for the Cmax and AUC0-t were 0.99 (0.82-1.18) and 1.04 (0.91-1.18), respectively. The overall results of the safety assessment showed no clinically significant issues for either treatment. The PK of HCP

  2. Comparison of the pharmacokinetics and tolerability of HCP1004 (a fixed-dose combination of naproxen and esomeprazole strontium and VIMOVO® (a marketed fixed-dose combination of naproxen and esomeprazole magnesium in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Choi YJ

    2015-07-01

    Full Text Available YoonJung Choi,1 HyeKyung Han,1 Dongseong Shin,2 Kyoung Soo Lim,3 Kyung-Sang Yu11Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, 2Clinical Trials Center, Gachon University Gil Medical Center, Incheon, 3Department of Clinical Pharmacology and Therapeutics, CHA Bundang Medical Center, CHA University, Seongnam, Republic of KoreaBackground: HCP1004 is a newly developed fixed-dose combination of naproxen (500 mg and esomeprazole strontium (20 mg that is used in the treatment of rheumatic diseases and can reduce the risk of nonsteroidal anti-inflammatory drug-associated ulcers. The aim of this study was to evaluate the pharmacokinetics (PK and safety of HCP1004 compared to VIMOVO® (a marketed fixed-dose combination of naproxen and esomeprazole magnesium.Subjects and methods: An open-label, randomized, two-treatment, two-sequence crossover, single-dose clinical study was conducted in 70 healthy volunteers. In each period, a reference (VIMOVO® or test (HCP1004 drug was administered orally, and serial blood samples for PK analysis were collected up to 72 hours after dosing. To evaluate the PK profiles, the maximum plasma concentration (Cmax and the area under the concentration–time curve from 0 to the last measurable time (AUC0-t were estimated using a noncompartmental method. Safety profiles were evaluated throughout the study.Results: Sixty-six of the 70 subjects completed the study. The Cmax (mean ± standard deviation and AUC0-t (mean ± standard deviation for naproxen in HCP1004 were 61.67±15.16 µg/mL and 1,206.52±166.46 h·µg/mL, respectively; in VIMOVO®; these values were 61.85±14.54 µg/mL and 1,211.44±170.01 h·µg/mL, respectively. The Cmax and AUC0-t for esomeprazole in HCP1004 were 658.21±510.91 ng/mL and 1,109.11±1,111.59 h·ng/mL, respectively; for VIMOVO®, these values were 595.09±364.23 ng/mL and 1,015.12±952.98 h·ng/mL, respectively. The geometric

  3. Anti-CD20 Cell Therapies in Multiple Sclerosis-A Fixed Dosing Schedule for Ocrelizumab is Overkill.

    Science.gov (United States)

    Avasarala, Jagannadha

    2017-01-01

    Anti-CD 20 therapies have found significant uses in multiple sclerosis (MS). Based singularly on the accumulated evidence with the use of rituximab (RTX; Rituxan, Genentech, and Biogen) in neuroimmunological diseases, ocrelizumab (OCR; Ocrevus, Genentech) was developed as a treatment option for MS and selectively targets CD20 B cells, a cell surface antigen found on pre-B cells, mature, and memory B cells, but not on lymphoid stem cells and plasma cells. On the basis of indirect evidence, elimination of the antigen-presenting capabilities and antigen nonspecific immune functions of B cells appear to be central to the therapeutic efficacy of anti-CD20 B-cell therapies. An important question is this-Why does the drug need to be dosed at fixed intervals and not based on a measurable endpoint, such as tracking peripheral CD20 cell counts? There is minimal scientific validity in infusing the drug every 6 months particularly if CD20 cell counts are negligible in the peripheral blood. In this analysis, a case is made for following CD19 cell populations as a surrogate for CD20 cells on a monthly basis to guide OCR redosing parameters and does not follow a scheduled dosing parameter.

  4. Anti-CD20 Cell Therapies in Multiple Sclerosis—A Fixed Dosing Schedule for Ocrelizumab is Overkill

    Science.gov (United States)

    Avasarala, Jagannadha

    2017-01-01

    Anti-CD 20 therapies have found significant uses in multiple sclerosis (MS). Based singularly on the accumulated evidence with the use of rituximab (RTX; Rituxan, Genentech, and Biogen) in neuroimmunological diseases, ocrelizumab (OCR; Ocrevus, Genentech) was developed as a treatment option for MS and selectively targets CD20 B cells, a cell surface antigen found on pre-B cells, mature, and memory B cells, but not on lymphoid stem cells and plasma cells. On the basis of indirect evidence, elimination of the antigen-presenting capabilities and antigen nonspecific immune functions of B cells appear to be central to the therapeutic efficacy of anti-CD20 B-cell therapies. An important question is this—Why does the drug need to be dosed at fixed intervals and not based on a measurable endpoint, such as tracking peripheral CD20 cell counts? There is minimal scientific validity in infusing the drug every 6 months particularly if CD20 cell counts are negligible in the peripheral blood. In this analysis, a case is made for following CD19 cell populations as a surrogate for CD20 cells on a monthly basis to guide OCR redosing parameters and does not follow a scheduled dosing parameter. PMID:29123374

  5. Prostaglandin analogs and timolol-fixed versus unfixed combinations or monotherapy for open-angle glaucoma: a systematic review and meta-analysis.

    Science.gov (United States)

    Quaranta, Luciano; Biagioli, Elena; Riva, Ivano; Rulli, Eliana; Poli, Davide; Katsanos, Andreas; Floriani, Irene

    2013-05-01

    To estimate the intraocular pressure (IOP)-lowering effect of prostaglandin analogs (PGAs) administered in combination with β-blockers. We searched the Medline and Embase databases for randomized trials comparing topical therapies with PGAs and timolol administered as monotherapy (Mt), or in fixed (FC) or unfixed combinations (UC) to patients with glaucoma or ocular hypertension. The efficacy endpoint was the mean difference (MeD) in the reduction in IOP from baseline; the tolerability endpoint was the incidence of hyperemia. The 18 eligible trials involved 23 comparisons of FC versus Mt, and 5 of FC versus UC. The FCs were less efficacious than UCs (MeD: 0.69, 95% CI: 0.29 to 1.08). In comparison with timolol Mt, the latanoprost/timolol FC led to a greater IOP reduction (MeD: -2.74, 95% CI: -3.24 to -2.23) than the bimatoprost/timolol FC (MeD: -1.49, 95% CI: -1.86 to -1.12) or the travoprost/timolol FC (MeD: -1.93, 95%CI: -2.98 to -0.88). The FCs led to a lower hyperemia risk than UCs [relative risk (RR): 0.70, 95% CI: 0.43 to 1.14] and PGA Mt (RR: 0.61, 95% CI: 0.53 to 0.70). FCs are more efficacious than their individual components, but less efficacious than their respective UCs. FCs lead to a lower hyperemia risk than UCs and their respective PGA Mts.

  6. Development of drug delivery systems for radionuclide therapy using a combination therapy

    Energy Technology Data Exchange (ETDEWEB)

    Kim, On Hee; Choi, Sun Ju [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    2005-07-01

    For the development of new controlled drug delivery systems, the application of combination therapy using angiogenesis inhibitor and tumor static agents has drawn great attention. This approach would be very beneficial for cancer treatment especially when a new drug deliver system utilizing biodegradable polymers is developed. Therefore, the present study for the combination therapy of angiogenesis inhibitor and chemotherapeutic agents was to carry out prior to the development of the novel drug delivery. In present study, the ability of inhibition on cell growth was investigated with treatment of anti-angiogenetic agent and anticancer agent. Thalidomide was used as an antivasculatory agents and Doxorubicine was treated as a chemotherapeutic agent. To demonstrate apoptotic process in in-vitro study, TUNEL assay was carried out. Also, the alteration of p53 level was examined by using western blotting. For the cell lines, NIH:OVCAR3, MKN45, SNU719, C6, L929, T98G, Hep3B and Calu6 were applied. Results showed that Thalidomide inhibited cell growth in tumor cell lines in a dose-dependent manner and Doxorubicin as well. A significant synergistic effect on the apoptotic was noticed in the combination treatment of Thalidomide and Doxorubicin compared to a single treatment of either drug. Therefore, it can be concluded that the mechanism of cytotoxicity was due to the enhancement of apoptosis in early cell death with combination treatment in tumor cell lines.

  7. Assessment of the changes in alveolar bone quality after fixed orthodontic therapy: A trabecular structure analysis

    Directory of Open Access Journals (Sweden)

    Abdolaziz Haghnegahdar

    2016-12-01

    Full Text Available Background. Tooth displacement changes the periodontium. The aim of orthodontic treatment is desired tooth movement with minimum side effects on the alveolar bone quality. The aim of the present study was to assess changes of alveolar trabeculation in children, young adults and adults and the two genders. Methods. In this cross-sectional study, 63 patients who had been treated in Department of Orthodontics, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran, were chosen with convenient sampling method. They were divided into three groups based on their age. Their digitized panoramic radiographs (PRs were evaluated at six interdental sites from the mesial aspect of the mandibular second molars to the distal aspect of the mandibular first premolars using a visual index. The trabeculation pattern was assigned as either dense (score 3, dense-sparse (score 2 or sparse (score 1. Data were imported to SPSS. Mean of the scores before treatment (score B and mean of them after treatment (score A were compared for each group with paired t-test. Changes between score B and sore A of the groups were compared using one-way ANOVA and post hoc tests. Results. Mean score A was significantly higher than mean score B in children (P = 0.001. In contrast, mean score A was significantly lower than mean score B in young adults (P = 0.003. Conclusion. Orthodontists should be cautious when treating young adults and adults regarding the probable, yet possibly temporary, negative effects of orthodontic therapy on the alveolar bone quality.

  8. Combination therapy in the management of atrophic acne scars

    Directory of Open Access Journals (Sweden)

    Shilpa Garg

    2014-01-01

    Full Text Available Background: Atrophic acne scars are difficult to treat. The demand for less invasive but highly effective treatment for scars is growing. Objective: To assess the efficacy of combination therapy using subcision, microneedling and 15% trichloroacetic acid (TCA peel in the management of atrophic scars. Materials and Methods: Fifty patients with atrophic acne scars were graded using Goodman and Baron Qualitative grading. After subcision, dermaroller and 15% TCA peel were performed alternatively at 2-weeks interval for a total of 6 sessions of each. Grading of acne scar photographs was done pretreatment and 1 month after last procedure. Patients own evaluation of improvement was assessed. Results: Out of 16 patients with Grade 4 scars, 10 (62.5% patients improved to Grade 2 and 6 (37.5% patients improved to Grade 3 scars. Out of 22 patients with Grade 3 scars, 5 (22.7% patients were left with no scars, 2 (9.1% patients improved to Grade 1and 15 (68.2% patients improved to Grade 2. All 11 (100% patients with Grade 2 scars were left with no scars. There was high level of patient satisfaction. Conclusion: This combination has shown good results in treating not only Grade 2 but also severe Grade 4 and 3 scars.

  9. Calcium dobesilate and oxerutin: effectiveness of combination therapy.

    Science.gov (United States)

    Akbulut, B

    2010-04-01

    with objective tests. Changes of quality of life after a combination therapy might also be of interest.

  10. 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

  11. Pharmacokinetics of two generic fixed-dose combinations for HIV-infected children (Pedimune Baby & Pedimune Junior) are similar to the branded products in healthy adults.

    NARCIS (Netherlands)

    L'homme, R.F.A.; Dijkema, T.; Warris, A.; Ven, A.J.A.M. van der; Gibb, D.M.; Burger, D.M.

    2007-01-01

    OBJECTIVES: Cipla Pharmaceuticals have developed generic fixed-dose combinations of stavudine, lamivudine and nevirapine for HIV-infected children (Pedimune Baby and Junior). We determined the pharmacokinetic profiles of stavudine, lamivudine and nevirapine in Pedimune and compared these with the

  12. 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

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

    National Research Council Canada - National Science Library

    Santiago Moreno Guillen; Juan Emilio Losa García; Juan Berenguer Berenguer; José Manuel Martínez Sesmero; Santiago Cenoz Gomis; Ruth Graefenhain; David Lopez Sanchez-Cambronero; Francisco Javier Parrondo Garcia

    2017-01-01

    ...) is a highly efficacious and well-tolerated once-daily regimen for HIV-infected patients. The objective of the study was to assess the incremental cost-utility ratio of the fixed-dose combination of (DTG/ABC/3TC...

  14. Strategies for nevirapine initiation in HIV-infected children taking pediatric fixed-dose combination "baby pills" in Zambia: a randomized controlled trial.

    NARCIS (Netherlands)

    Mulenga, V.; Cook, A.; Walker, A.S.; Kabamba, D.; Chijoka, C.; Ferrier, A.; Kalengo, C.; Kityo, C.; Kankasa, C.; Burger, D.M.; Thomason, M.; Chintu, C.; Gibb, D.M.

    2010-01-01

    BACKGROUND: Fixed-dose combination scored dispersible stavudine, lamivudine, and nevirapine minitablets (Triomune Baby and Junior; Cipla Ltd) are simpler and cheaper than liquid formulations and have correct dose ratios for human immunodeficiency virus-infected children. However, they cannot be used

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

    NARCIS (Netherlands)

    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

  16. DPP-4 inhibitor plus SGLT-2 inhibitor as combination therapy for type 2 diabetes: from rationale to clinical aspects.

    Science.gov (United States)

    Scheen, André J

    2016-12-01

    Type 2 diabetes (T2D) is a complex disease with multiple defects, which generally require a combination of several pharmacological approaches to control hyperglycemia. Combining a dipeptidyl peptidase-4 inhibitor (DPP-4i) and a sodium-glucose cotransporter type 2 inhibitor (SGT2i) appears to be an attractive approach. Area covered: An extensive literature search was performed to analyze the pharmacokinetics, pharmacodynamics and clinical experience of different gliptin-gliflozin combinations. Expert opinion: There is a strong rationale for combining a DPP-4i and a SGLT2i in patients with T2D because the two drugs exert different and complementary glucose-lowering effects. Dual therapy (initial combination or stepwise approach) is more potent than either monotherapy in patients treated with diet and exercise or already treated with metformin. Combining the two pharmacological options is safe and does not induce hypoglycemia. The additional glucose-lowering effect is more marked when a gliflozin is added to a gliptin than when a gliptin is added to a gliflozin. Two fixed-dose combinations (FDCs) are already available (saxagliptin-dapagliflozin and linagliptin-empagliflozin) and others are in current development. Bioequivalence of the two compounds given as FDC tablets was demonstrated when compared with coadministration of the individual tablets. FDCs could simplify the anti-hyperglycaemic therapy and improve drug compliance.

  17. Effects of Latanoprost 0.005%/Timolol Maleate 0.5% and Dorzolamide 2%/Timolol Maleate 0.5% Fixed Combinations on 24-hour Intraocular Pressure in Patients with Primary Open-Angle Glaucoma

    Directory of Open Access Journals (Sweden)

    Berna Yüce

    2012-01-01

    Full Text Available Pur po se: To evaluate the effects of latanoprost/timolol maleate and dorzolamid/timolol maleate fixed combinations on-24 hours intraocular pressure in patients with open-angle glaucoma. Ma te ri als and Met hod: Forty-eight eyes of 24 patients with open-angle glaucoma were enrolled in the study. They were randomized to receive fixed combinations of either latanoprost/timolol maleate (Group 1 - 24 eyes of 12 patients or dorzolamid/timolol maleate (Group 2 - 24 eyes of 12 patients. Patients who achieved intraocular pressure of ≤ 21 mmHg 3 weeks after combined therapy were hospitalized and intraocular pressure was monitored at hour 06:00, 10:00, 14:00, 18:00, 22:00 and 02:00 for 24 hours. Diurnal and nocturnal fluctuations were determined by measurements done between 06:00 and 18:00 hours and between 22:00 and 02:00, respectively. Mean intraocular pressure and fluctuations of intraocular pressure between the two groups were compared. Re sults: There was no difference between the groups in terms of age, sex, visual acuity and cup/disc ratio (p>0.05. Three weeks after combined therapy, all patients achieved target intraocular pressure of ≤ 21 mmHg. There was no statistically significant difference between the two groups with regard to mean intraocular pressure over 24 hours (17.1±2.3 mmHg and 17.27±2.3 mmHg for Group 1 and Group 2, respectively; p>0.05. Diurnal fluctuations were 3.6 mmHg for Group 1 and 4.7 mmHg for Group 2; nocturnal fluctuations were 4.3 mmHg for Group 1 and 2.3 mmHg for Group 2. Diurnal fluctuations in Group 1 were lower than in Group 2, while nocturnal fluctuations were lower in Group 2 than in Group 1 (p<0.05. Dis cus si on: Both latanoprost/timolol maleate and dorzolamid/timolol maleate fixed combinations are effective for 24-hour intraocular pressure control. Latanoprost/timolol maleate fixed combination is superior to dorzolamid/timolol maleate in controlling diurnal fluctuations, while dorzolamid/timolol maleate is

  18. Transarterial chemoembolization in combination with local therapies for hepatocellular carcinoma: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Mingheng Liao

    Full Text Available BACKGROUND: In previous randomized trials, transarterial chemoembolization (TACE has shown an improvement of survival rate in hepatocellular carcinoma (HCC when combined with radiofrequency ablation (RFA, percutaneous ethanol injection (PEI or other therapies. The aim of this meta-analysis was to evaluate the effectiveness of combination therapy of TACE with RFA, PEI, radiotherapy (RT, three-dimensional conformal radiation therapy (3D-CRT or High-Intensity Focused Ultrasound (HIFU. METHODS: Randomized or nonrandomized studies comparing TACE combined with RFA, PEI, RT, 3D-CRT or HIFU with TACE alone for HCC were included. Meta-analysis was performed using a fix-effects model in RCTs and a random-effects model among the observational studies. RESULTS: 10 randomized trials and 18 observational studies matched the selection criteria, including 2497 patients (682 in RCTs, 1815 in non-RCTs. Meta-analysis of RCTs showed that the combination of TACE and PEI ((RR(1-year=1.10, 95%CI=0.99-1.22, p=0.073; (RR(3-year=2.32, 95%CI=1.52-3.53, p<0.001, TACE+RT ((RR(1-year=1.37, 95%CI=1.11-1.70, p=0.004; (RR(3-year=2.32, 95%CI=1.44-3.75, p=0.001 were associated with higher survival rates. The results of observational studies were in good consistency with that of RCTs. Furthermore, TACE plus 3D-CRT ((RR1 -year=1.22, 95%CI=1.06-1.41, p=0.005; (RR(3-year=2.05, 95%CI=1.48-2.84, p<0.001 and TACE plus HIFU ((RR(1-year=1.16, 95%CI=1.01-1.33, p=0.033; (RR(3-year=1.66, 95%CI=1.12-2.45, p=0.011 have introduced marked survival benefit when pooling results from observational studies. CONCLUSIONS: This meta-analysis demonstrated that TACE combined with local treatments, especially PEI, HIFU or 3D-CRT could improve the overall survival status than performing TACE alone. Importantly, these results need to be validated in further high-quality clinical trials.

  19. Fixed combination brimonidine-timolol versus brimonidine for treatment of intraocular pressure elevation after neodymium:YAG laser posterior capsulotomy.

    Science.gov (United States)

    Öner, Veysi; Alakuş, Mehmet Fuat; Taş, Mehmet; Türkyılmaz, Kemal; Işcan, Yalçın

    2012-12-01

    To evaluate the efficacy of fixed combination brimonidine-timolol (FCBT) in comparison with brimonidine tartrate 0.2% and control for the treatment of intraocular pressure (IOP) spikes after neodymium:YAG (Nd:YAG) laser posterior capsulotomy. One hundred five eyes of 105 patients were enrolled in the study. Patients were randomized to 3 groups (each group, including 35 patients): the FCBT group that received 1 drop of FCBT, the brimonidine group that received 1 drop of brimonidine tartrate 0.2%, and the control group that received 1 drop of artificial tear, 1 h before the laser procedure. Postoperative IOP measurements were performed at 1st, 2nd, 3rd, 24th hours, and seventh day. The mean IOP changes from baseline were statistically different between the study groups at first, second, and third hours (all P0.05), the IOP levels of the brimonidine group were less reduced from baseline than the FCBT group at second and third hours (P=0.01 and P=0.03, respectively). The differences among the study groups concerning the incidence of IOP elevations of ≥5 or ≥10 mmHg were statistically significant (P=0.007, P=0.04, respectively). However, the differences between the treatment groups were not statistically significant (both P>0.05). This study has shown that preoperative instillation of 1-drop FCBT was safe and effective for preventing IOP spikes after Nd:YAG laser posterior capsulotomy. FCBT may be a better option than brimonidine tartrate 0.2%, which is one of the current standard prophylaxes for these spikes.

  20. The 24-Hour Effects of Brinzolamide/Brimonidine Fixed Combination and Timolol on Intraocular Pressure and Ocular Perfusion Pressure.

    Science.gov (United States)

    Seibold, Leonard K; DeWitt, Peter E; Kroehl, Miranda E; Kahook, Malik Y

    2017-04-01

    To determine the 24-h effects of brinzolamide/brimonidine tartrate 1%/0.2% fixed combination (BBFC) on intraocular pressure (IOP), ocular perfusion pressure (OPP), blood pressure (BP), and heart rate (HR). Sixty subjects with open angle glaucoma (OAG) or ocular hypertension (OHTN) were admitted overnight for 24-h monitoring of IOP, BP, and HR. All subjects underwent the first, baseline 24-h study after washout of all medications, if necessary. Subjects were then randomized to receive either (1) timolol maleate 0.5% twice daily or (2) BBFC 3 times daily. After 4 weeks of treatment, all subjects completed a follow-up 24-h study visit. At each study visit, IOP, BP, and HR were measured every 2 h in the habitual position. OPP was calculated as 2/3[diastolic BP +1/3(systolic BP-diastolic BP)]-IOP. Treatment with BBFC significantly lowered IOP during the diurnal period (-2.7 ± 0.4 mmHg; P < 0.01) and nocturnal period (-0.8 ± 0.3 mmHg; P < 0.01). Timolol similarly reduced IOP during the diurnal period, but did not lower IOP overnight. Over a 24-h period, BBFC achieved a significantly greater IOP reduction than timolol (-0.7 ± 0.4 mmHg; P = 0.04). BBFC failed to achieve an increase in OPP during any time period, while timolol increased OPP during the diurnal period only. A significantly greater reduction in HR occurred in the timolol group. BBFC significantly lowers IOP during both the diurnal and nocturnal periods, but has no effect on OPP. Timolol only lowers IOP during the diurnal period.

  1. Drug-drug interaction profile of components of a fixed combination of netupitant and palonosetron: Review of clinical data.

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    Natale, James J; Spinelli, Tulla; Calcagnile, Selma; Lanzarotti, Corinna; Rossi, Giorgia; Cox, David; Kashef, Kimia

    2016-06-01

    Neurokinin-1 (NK1) receptor antagonists (RAs) are commonly coadministered with serotonin (5-HT3) RAs (e.g. palonosetron (PALO)) to prevent chemotherapy-induced nausea/vomiting. Netupitant/palonosetron (NEPA), an oral fixed combination of netupitant (NETU)-a new NK1 RA-and PALO, is currently under development. In vitro data suggest that NETU inhibits CYP3A4 and is a substrate for and weak inhibitor of P-glycoprotein (P-gp). This review evaluates potential drug-drug interactions between NETU or NEPA and CYP3A4 substrates/inducers/inhibitors or P-gp substrates in healthy subjects. Pharmacokinetic (PK) parameters were evaluated for each drug when NETU was coadministered with PALO (single doses) and when single doses of NETU or NEPA were coadministered with CYP3A4 substrates (erythromycin (ERY), midazolam (MID), dexamethasone (DEX), or oral contraceptives), inhibitors (ketoconazole (KETO)), or inducers (rifampicin (RIF)), or a P-gp substrate (digoxin (DIG)). Results showed no relevant PK interactions between NETU and PALO. Coadministration of NETU increased MID and ERY exposure and significantly increased DEX exposure in a dose-dependent manner; NETU exposure was unaffected. NEPA coadministration had no clinically significant effect on oral contraception, although levonorgestrel exposure increased. NETU exposure increased after coadministration of NEPA with KETO and decreased after coadministration with RIF; PALO exposure was unaffected. NETU coadministration did not influence DIG exposure. In conclusion, there were no clinically relevant interactions between NETU and PALO, or NEPA and oral contraceptives (based on levonorgestrel and ethinylestradiol exposure). Coadministration of NETU or NEPA with CYP3A4 inducers/inhibitors/substrates should be done with caution. Dose reduction is recommended for DEX. Dose adjustments are not needed for NETU coadministration with P-gp substrates. © The Author(s) 2015.

  2. Drug–drug interaction profile of components of a fixed combination of netupitant and palonosetron: Review of clinical data

    Science.gov (United States)

    Spinelli, Tulla; Calcagnile, Selma; Lanzarotti, Corinna; Rossi, Giorgia; Cox, David; Kashef, Kimia

    2015-01-01

    Neurokinin-1 (NK1) receptor antagonists (RAs) are commonly coadministered with serotonin (5-HT3) RAs (e.g. palonosetron (PALO)) to prevent chemotherapy-induced nausea/vomiting. Netupitant/palonosetron (NEPA), an oral fixed combination of netupitant (NETU)—a new NK1 RA—and PALO, is currently under development. In vitro data suggest that NETU inhibits CYP3A4 and is a substrate for and weak inhibitor of P-glycoprotein (P-gp). This review evaluates potential drug–drug interactions between NETU or NEPA and CYP3A4 substrates/inducers/inhibitors or P-gp substrates in healthy subjects. Pharmacokinetic (PK) parameters were evaluated for each drug when NETU was coadministered with PALO (single doses) and when single doses of NETU or NEPA were coadministered with CYP3A4 substrates (erythromycin (ERY), midazolam (MID), dexamethasone (DEX), or oral contraceptives), inhibitors (ketoconazole (KETO)), or inducers (rifampicin (RIF)), or a P-gp substrate (digoxin (DIG)). Results showed no relevant PK interactions between NETU and PALO. Coadministration of NETU increased MID and ERY exposure and significantly increased DEX exposure in a dose-dependent manner; NETU exposure was unaffected. NEPA coadministration had no clinically significant effect on oral contraception, although levonorgestrel exposure increased. NETU exposure increased after coadministration of NEPA with KETO and decreased after coadministration with RIF; PALO exposure was unaffected. NETU coadministration did not influence DIG exposure. In conclusion, there were no clinically relevant interactions between NETU and PALO, or NEPA and oral contraceptives (based on levonorgestrel and ethinylestradiol exposure). Coadministration of NETU or NEPA with CYP3A4 inducers/inhibitors/substrates should be done with caution. Dose reduction is recommended for DEX. Dose adjustments are not needed for NETU coadministration with P-gp substrates. PMID:25998320

  3. Pharmacokinetics and bioequivalence study of a fixed dose combination of rabeprazole and itopride in healthy Indian volunteers.

    Science.gov (United States)

    Sahoo, Bijay Kumar; Das, Ayan; Agarwal, Sangita; Bhaumik, Uttam; Bose, Anirbandeep; Ghosh, Debotri; Roy, Bikash; Pal, Tapan Kumar

    2009-01-01

    The aim of the present study was to compare the pharmacokinetics of rabeprazole (CAS 117976-89-3) and itopride (CAS 122898-67-3) after oral administration of a rabeprazole (20 mg)-itopride (150 mg) fixed dose combination (FDC) in healthy human volunteers. The bioequivalence of two formulations (test and reference) was determined in 12 healthy Indian male volunteers (age: 25.25 +/- 4.69 years; weight: 60.50 +/- 5.04 kg) in a randomized, single-dose, two-period, two-treatment crossover study. Both formulations were administered orally as a single dose, with the treatments separated by a washout period of 1 week. Rabeprazole and itopride plasma levels were determined by a validated HPLC method using UV detection. The formulations were compared using the pharmacokinetic parameters area under the plasma concentration-time curve (AUC(0-t)), area under the plasma concentration-time curve from zero to infinity (AUC(0-infinity)) and peak plasma concentration (Cmax). General linear model (GLM) procedures were used in which sources of variation were subject, treatment and period. The results indicated that there were no statistically significant differences (P > 0.05) between the logarithmically transformed AUC(0-infinity) and Cmax values between test and reference formulation. The 90% confidence interval for the ratio of the logarithmically transformed AUC(0-t), AUC(0-infinity) and Cmax were within the bioequivalence limits of 0.8-1.25 and the relative bioavailability of rabeprazole and itopride test and reference formulations was 98.24 and 93.65%, respectively.

  4. Study of the efficacy, tolerability, and safety of 2 fixed-dose combination gels in the management of acne vulgaris.

    Science.gov (United States)

    Zouboulis, Christos C; Fischer, Tanja C; Wohlrab, Johannes; Barnard, Jo; Alió, Alessandra B

    2009-10-01

    This study investigated the efficacy, tolerability, and safety of 2 fixed-dose combination gels for the treatment of facial acne: clindamycin 1%-benzoyl peroxide 5% gel with hydrating excipients (C/BPO HE) and adapalene 0.1%-benzoyl peroxide 25% gel (A/BPO). After 12 weeks of once daily treatment, the mean reduction in inflammatory lesion count was 76.8% and 72.2% in the C/BPO HE group and A/BPO group, respectively (P = .076). Significantly more participants achieved treatment success, which was defined as an improvement of 2 grades or more from baseline to week 12 on the investigator's static global assessment (ISGA) scale, with C/BPO HE (30.5% [58/190]) compared with A/BPO (21.8% [42/192]) (P = .046), and treatment success was achieved more quickly with C/BPO HE (P = .035). Both products also reduced noninflammatory (62.2% C/BPO HE vs 6 1.5% A/BPO) and total lesion counts (69.1% C/BPO HE vs 67.1% A/BPO). Despite the overall similar efficacy profile, C/BPO HE was better tolerated and safer than A/BPO. In the tolerability assessments, erythema, dryness, peeling, pruritus, and burning/ stinging were more frequent in the A/BPO group at all time points from week 1 onward (P < .05). Treatment-related adverse events (AEs) occurred in 48.4% (92/190) of participants in the C/BPO HE group compared with 78.6% (151/192) of the A/BPO group. We conclude that C/BPO HE and A/BPO have similar efficacy in treating inflammatory and noninflammatory acne lesions, but C/BPO HE achieves better overall treatment success in less time coupled with a significantly better tolerability profile and notably better safety profile.

  5. Clinical Pharmacokinetics and Pharmacodynamics of Ledipasvir/Sofosbuvir, a Fixed-Dose Combination Tablet for the Treatment of Hepatitis C.

    Science.gov (United States)

    German, Polina; Mathias, Anita; Brainard, Diana; Kearney, Brian P

    2016-11-01

    Ledipasvir/sofosbuvir (Harvoni ® ), a fixed-dose combination tablet of an NS5A inhibitor ledipasvir and an NS5B polymerase inhibitor sofosbuvir, is approved in the US, European Union, Canada, and other regions for the treatment of chronic hepatitis C virus infection in adults. Following absorption, ledipasvir reaches maximum plasma concentrations (T max ) 4-4.5 h post-dose and is eliminated with a terminal half-life (t 1/2 ) of 47 h. Sofosbuvir undergoes intracellular activation to an active triphosphate GS-461203 (not detected in plasma) and ultimately to GS-331007, a predominant circulating metabolite, which is the primary analyte of interest in clinical pharmacology studies. Sofosbuvir is rapidly absorbed and eliminated from plasma (T max : 0.8-1 h; t 1/2 : 0.5 h). The peak plasma concentrations for GS-331007 are achieved between 3.5 and 4 h post-dose; the elimination t 1/2 for GS-331007 is 27 h. Ledipasvir/sofosbuvir exhibits a favorable clinical pharmacology profile; it can be administered once daily without regard to food and does not require dose modification in hepatitis C virus-infected patients with any degree of hepatic impairment or mild to moderate renal impairment. The pharmacokinetic profiles of ledipasvir, sofosbuvir, and GS-331007 (predominant circulating metabolite of sofosbuvir) are not significantly affected by demographic variables; pharmacokinetic/pharmacodynamic analyses reveal no exposure-response relationships for efficacy or safety. The review summarizes the clinical pharmacokinetics, pharmacodynamics, and pharmacokinetic/pharmacodynamic analyses for ledipasvir/sofosbuvir.

  6. Pharmacokinetic study of metformin to compare a voglibose/metformin fixed-dose combination with coadministered voglibose and metformin

    Science.gov (United States)

    Choi, Hyang-Ki; Oh, Minkyung; Kim, Eun Ji; Song, Geun Seog; Ghim, Jong-lyul; Shon, Ji-Hong; Kim, Ho-Sook; Shin, Jae-Gook

    2015-01-01

    The aim of this study was to compare the pharmacokinetic characteristics of metformin between a fixed-dose combination (FDC) of voglibose/metformin and co-administered individual voglibose and metformin tablets in healthy Korean volunteers under fasting conditions. A randomized, open-label, single-dose, two-treatment, two-way crossover study with a 7-day wash-out period was conducted. Plasma samples were collected for up to 24 hours and were analyzed for metformin using a validated liquid chromatography tandem mass-spectrometry (LC/MS). A non-compartmental method was used to calculate the pharmacokinetic parameters. Vital signs and adverse events were monitored, and physical examinations and laboratory tests were conducted to evaluate safety. In total, 28 subjects completed the study. The geometric mean ratio (GMR) and the 90% confidence interval (CIs) of Cmax and AUC0–t of metformin were 102.4 (94.5 – 111.0) and 107.1 (100.1 – 114.7), respectively. In total, 7 adverse drug reactions occurred in 4 subjects during the study; of these, 3 cases were from 3 subjects in the test treatment group, and 4 cases were from 3 subjects in the reference treatment group. All adverse drug reactions had been reported previously, and all subjects recovered fully without any sequelae. In conclusion, the pharmacokinetic profiles of metformin in two different study treatments, a voglibose/metformin FDC vs. the coadministration of the individual formulations, met the regulatory criteria for bioequivalence in healthy Korean subjects under fasting conditions. There was no significant difference in safety profiles between the two treatments. PMID:25546164

  7. Therapy of Severe Heatshock in Combination With Multiple Organ Dysfunction With Continuous Renal Replacement Therapy

    Science.gov (United States)

    Chen, Guang-Ming; Chen, Yang-Hong; Zhang, Wei; Yu, Yi; Chen, Jin-Hua; Chen, Jian

    2015-01-01

    Abstract This study aimed to compare the clinical effects of continuous renal replacement therapy (CRRT) and routine therapy in heatshock (HS) patients. We retrospectively reviewed the clinical information of 33 severe exertional HS patients who were treated from February 1998 to October 2013. On the basis of whether or not CRRT therapy was used in addition to conventional therapy, patients were divided into a CRRT group (n = 15) and a control group (n = 18). Body temperature, blood gas analysis, routine blood tests, blood eletrolytes, enzymes and kidney function data, and APACHE II scores were obtained and compared between the 2 groups on admission and 3, 5, and 7 days after admission. Mortality was also compared between the 2 groups. CRRT treatment combined with conventional treatment resulted in a higher hospital-discharge rate, a faster return to normal of body temperature, greater increase in platelets, a greater decrease in WBC, neutrophils, and serum markers for liver and kidney dysfunction, greater improvement of organ dysfunction, and lower APACHE II scores than conventional treatment used alone. The addition of CRRT to conventional treatment for HS improves survival and causes a faster return to normal of serum markers and organ function. PMID:26252279

  8. Efficacy of Olanzapine Combined Therapy for Patients Receiving Highly Emetogenic Chemotherapy Resistant to Standard Antiemetic Therapy.

    Science.gov (United States)

    Abe, Masakazu; Kasamatsu, Yuka; Kado, Nobuhiro; Kuji, Shiho; Tanaka, Aki; Takahashi, Nobutaka; Takekuma, Munetaka; Hirashima, Yasuyuki

    2015-01-01

    Olanzapine is proved to be effective for chemotherapy induced nausea and vomiting (CINV). But its efficacy in combination with standard antiemetic therapy is unknown. The purpose of this study is to prove the preventive effect of olanzapine for the prevention of CINV caused by highly emetogenic chemotherapy when used with standard antiemetic therapy. Gynecologic cancer patients receiving cisplatin-based chemotherapy who had grade 2 or 3 nausea in overall phase (0-120 h after chemotherapy) despite standard therapy were assigned to this study. From the next cycles to cycles in which patients developed grade 2 or 3 nausea, they received olanzapine with standard therapy. 5 mg oral olanzapine was administered for 7 days from the day before chemotherapy. The effectiveness of preventive administration of olanzapine was evaluated retrospectively. The primary endpoint was nausea control rate (grade 0 or 1) with olanzapine. Fifty patients were evaluable. The nausea control rate with olanzapine was improved from 58% to 98% in acute phase (0-24 h after chemotherapy) and 2% to 94% in delayed phase (24-120 h after chemotherapy). In overall phase, the nausea control rate improved from 0% to 92%, and it was statistically significant (P improvement in control of refractory nausea.

  9. Evaluation of vildagliptin and fixed dose combination of vildagliptin and metformin on glycemic control and insulin dose over 3 months in patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Paresh Ved

    2012-01-01

    Full Text Available Objective: Addition of vildagliptin to ongoing insulin therapy may help in terms of overall glycemic control as well as reduction in dose of insulin and weight. This study sought to evaluate the effect of vildagliptin and fixed dose combination (FDC of vildagliptin and metformin in patients in ongoing insulin therapy for Type 2 diabetes mellitus. Materials and Methods: This was an open label, prospective, non-randomised, multicentric observational study. In this study 400 patients with T2DM on insulin were enrolled and allocated with the treatment of vildagliptin 50 mg in monotherapy and FDC of vildagliptin 50 mg and metformin strengths as 500/ 850 / 1000 mg. Baseline investigations included fasting blood glucose (FBG and post prandial plasma glucose (PPPG Estimation and glycosylated haemoglobin (HbA1c. Results: The combined analysis was carried out on 300 completed patients in this study, who were treated with vildagliptin or FDC of vildagliptin and metformin. The difference in mean value of insulin dose (MID showed a highly significant decrease (P <0.0001 from baseline to end of the treatment i.e. from 36.26 ± 18.21 to 26.87 ± 16.49 IU. A highly significant decrease (P <0.0001 in FBG from 194.94 ± 56.19 to 124.93 ± 30.11 mg/dl was observed. Similarly PPPG showed a highly significant (P <0.0001 decrease from baseline to end of the treatment i.e. from 287.60 mg/dl to 172.05 mg/dl and there was highly significant (P <0.0001 decrease in HbA1c i.e. from 9.01% to 7.65% respectively. At the same time, highly significant decrease (P <0.0001 in mean weight also observed from baseline to end of the treatment i.e. from 71.23 ± 11.06 kg to 70.06 ± 10.62 Kg. Conclusion: Addition of vildagliptin and FDC of vildagliptin and metformin is an effective strategy in glycemic control, reduction in dose of insulin and weight of patients suffering with T2DM.

  10. Combining angiogenic gene and stem cell therapies for myocardial infarction.

    Science.gov (United States)

    Pons, Jennifer; Huang, Yu; Takagawa, Junya; Arakawa-Hoyt, Janice; Ye, Jianqin; Grossman, William; Kan, Yuet Wai; Su, Hua

    2009-09-01

    Transplantation of stem cells from various sources into infarcted hearts has the potential to promote myocardial regeneration. However, the regenerative capacity is limited partly as a result of the low survival rate of the transplanted cells in the ischemic myocardium. In the present study, we tested the hypothesis that combining cell and angiogenic gene therapies would provide additive therapeutic effects via co-injection of bone marrow-derived mesenchymal stem cells (MSCs) with an adeno-associated viral vector (AAV), MLCVEGF, which expresses vascular endothelial growth factor (VEGF) in a cardiac-specific and hypoxia-inducible manner. MSCs isolated from transgenic mice expressing green fluorescent protein and MLCVEGF packaged in AAV serotype 1 capsid were injected into mouse hearts at the border of ischemic area, immediately after occlusion of the left anterior descending coronary, individually or together. Engrafted cells were detected and quantified by real-time polymerase chain reaction and immunostaining. Angiogenesis and infarct size were analyzed on histological and immunohistochemical stained sections. Cardiac function was analyzed by echocardiography. We found that co-injection of AAV1-MLCVEGF with MSCs reduced cell loss. Although injection of MSCs and AAV1-MLCVEGF individually improved cardiac function and reduced infarct size, co-injection of MSC and AAV1-MLCVEGF resulted in the best improvement in cardiac function as well as the smallest infarct among all groups. Moreover, injection of AAV1-MLCVEGF induced neovasculatures. Nonetheless, injection of MSCs attracted endogenous stem cell homing and increased scar thickness. Co-injection of MLCVEGF and MSCs in ischemic hearts can result in better cardiac function and MSC survival, compared to their individual injections, as a result of the additive effects of each therapy.

  11. Cognitive behavioral therapy in combination with systemic family therapy improves mild to moderate postpartum depression

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    Yongmei Hou

    2014-03-01

    Full Text Available Objective: To explore the effect of cognitive behavioral therapy (CBT in combination with systemic family therapy (SFT on mild to moderate postpartum depression and sleep quality. Methods: 249 primiparous women with mild to moderate postpartum depression were recruited and randomly assigned to a control group (n=128, which received conventional postpartum care, or to a psychological intervention group (n=121, which received conventional postpartum care combined with psychological intervention. The Edinburgh Postnatal Depression Scale (EPDS and Pittsburgh Sleep Quality Index (PSQI were employed to evaluate depression and sleep quality, respectively. Results: 104 patients in the intervention group and 109 in the control group completed the study. After intervention, the EPDS score, PSQI score, sleep quality score, sleep latency score, sleep duration score, habitual sleep efficiency score, sleep disturbance score, and daytime dysfunction score were significantly lower in the intervention group than in the control group. The EPDS and PSQI scores of each group at different time points after intervention were markedly decreased compared with those before intervention, and the reduction in the intervention group was more evident than that in the control group. Conclusion: CBT in combination with SFT can improve depression and sleep quality in patients with mild to moderate postpartum depression.

  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

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    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. Effects of candesartan and propranolol combination therapy versus propranolol monotherapy in reducing portal hypertension.

    Science.gov (United States)

    Kim, Jae Hyun; Kim, Jung Min; Cho, Youn Zoo; Na, Ji Hoon; Kim, Hyun Sik; Kim, Hyoun A; Kang, Hye Won; Baik, Soon Koo; Kwon, Sang Ok; Cha, Seung Hwan; Kim, Young Ju; Kim, Moon Young

    2014-12-01

    Angiotensin receptor blockers (ARBs) inhibit activated hepatic stellate cell contraction and are thought to reduce the dynamic portion of intrahepatic resistance. This study compared the effects of combined treatment using the ARB candesartan and propranolol versus propranolol monotherapy on portal pressure in patients with cirrhosis in a prospective, randomized controlled trial. Between January 2008 and July 2009, 53 cirrhotic patients with clinically significant portal hypertension were randomized to receive either candesartan and propranolol combination therapy (26 patients) or propranolol monotherapy (27 patients). Before and 3 months after the administration of the planned medication, the hepatic venous pressure gradient (HVPG) was assessed in both groups. The dose of propranolol was subsequently increased from 20 mg bid until the target heart rate was reached, and the candesartan dose was fixed at 8 mg qd. The primary endpoint was the HVPG response rate; patients with an HVPG reduction of >20% of the baseline value or to candesartan (an ARB) to propranolol confers no benefit relative to classical propranolol monotherapy for the treatment of portal hypertension, and is thus not recommended.

  14. Multimodal therapy for painful bladder syndrome / interstitial cystitis: pilot study combining behavioral, pharmacologic, and endoscopic therapies

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    Robert S. Hanley

    2009-08-01

    Full Text Available Purpose: We evaluated the effectiveness of combining behavioral therapy, pharmacologic therapy and endoscopic hydrodistension for treating painful bladder syndrome / interstitial cystitis (PBS/IC. Materials and Methods: Twenty-five patients with PBS/IC were prospectively enrolled in a pilot multimodal behavioral, pharmacologic and endoscopic treatment protocol. Behavioral modification included diet recommendations, fluid restriction to 64 oz. /day, progressive timed voiding and Kegel exercises. Oral pharmacologic therapy consisted of daily doses of macrodantin 100 mg, hydroxyzine 10-20 mg and urised 4 tablets. Patients underwent endoscopic bladder hydrodistention under anesthesia at least 2 weeks after protocol enrollment. Behavioral and pharmacological treatments were continued after the hydrodistention. O'Leary-Sant questionnaire scores were recorded before starting the protocol, after pharmacologic/behavioral therapy, 2 months post-hydrodistension, and at scheduled follow-up. Results: Eighteen patients (72% completed the pilot multimodal treatment protocol and were followed for a mean of 10.2 months. All patients were female with a median age of 36.3 years and had mean bladder capacity under anesthesia of 836 milliliters. Mean O'Leary-Sant symptom index scores for baseline symptoms, after behavioral/pharmacologic treatment, post-hydrodistension and during follow up were 12.5, 8.6, 7.0, and 6.7 (p < 0.05. Mean O'Leary-Sant problem index scores for baseline, after behavioral/pharmacologic treatment, post-hydrodistention and during follow up were 12.7, 8.9, 6.7, and 7.7 (p < 0.05. Conclusion: Our pilot multimodal protocol of behavioral modification, pharmacologic therapy and endoscopic hydrodistention demonstrated a significant progressive improvement in PBS/IC quality of life scores, compared to a pre-treatment baseline. These results should be validated in a larger, placebo controlled trial.

  15. Multimodal therapy for painful bladder syndrome / interstitial cystitis: pilot study combining behavioral, pharmacologic, and endoscopic therapies.

    Science.gov (United States)

    Hanley, Robert S; Stoffel, John T; Zagha, Ralph M; Mourtzinos, Arthur; Bresette, John F

    2009-01-01

    We evaluated the effectiveness of combining behavioral therapy, pharmacologic therapy and endoscopic hydrodistension for treating painful bladder syndrome / interstitial cystitis (PBS/IC). Twenty-five patients with PBS/IC were prospectively enrolled in a pilot multimodal behavioral, pharmacologic and endoscopic treatment protocol. Behavioral modification included diet recommendations, fluid restriction to 64 oz. /day, progressive timed voiding and Kegel exercises. Oral pharmacologic therapy consisted of daily doses of macrodantin 100 mg, hydroxyzine 10-20 mg and urised 4 tablets. Patients underwent endoscopic bladder hydrodistention under anesthesia at least 2 weeks after protocol enrollment. Behavioral and pharmacological treatments were continued after the hydrodistention. O'Leary-Sant questionnaire scores were recorded before starting the protocol, after pharmacologic/behavioral therapy, 2 months post-hydrodistension, and at scheduled follow-up. Eighteen patients (72%) completed the pilot multimodal treatment protocol and were followed for a mean of 10.2 months. All patients were female with a median age of 36.3 years and had mean bladder capacity under anesthesia of 836 milliliters. Mean O'Leary-Sant symptom index scores for baseline symptoms, after behavioral/pharmacologic treatment, post-hydrodistension and during follow up were 12.5, 8.6, 7.0, and 6.7 (p < 0.05). Mean O'Leary-Sant problem index scores for baseline, after behavioral/pharmacologic treatment, post-hydrodistention and during follow up were 12.7, 8.9, 6.7, and 7.7 (p < 0.05). Our pilot multimodal protocol of behavioral modification, pharmacologic therapy and endoscopic hydrodistention demonstrated a significant progressive improvement in PBS/IC quality of life scores, compared to a pre-treatment baseline. These results should be validated in a larger, placebo controlled trial.

  16. Long-term follow-up of severely symptomatic women with adenomyoma treated with combination therapy

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    Wei-Min Liu

    2013-03-01

    Conclusion: Combination therapy for adenomyoma provides an effective treatment option for long-term symptom control and uterine preservation in severely symptomatic women for whom previous long-term drug therapy has failed or proven to be intolerable.

  17. Nanomedicine-based combination anticancer therapy between nucleic acids and small-molecular drugs.

    Science.gov (United States)

    Huang, Wei; Chen, Liqing; Kang, Lin; Jin, Mingji; Sun, Ping; Xin, Xin; Gao, Zhonggao; Bae, You Han

    2017-06-01

    Anticancer therapy has always been a vital challenge for the development of nanomedicine. Repeated single therapeutic agent may lead to undesirable and severe side effects, unbearable toxicity and multidrug resistance due to complex nature of tumor. Nanomedicine-based combination anticancer therapy can synergistically improve antitumor outcomes through multiple-target therapy, decreasing the dose of each therapeutic agent and reducing side effects. There are versatile combinational anticancer strategies such as chemotherapeutic combination, nucleic acid-based co-delivery, intrinsic sensitive and extrinsic stimulus combinational patterns. Based on these combination strategies, various nanocarriers and drug delivery systems were engineered to carry out the efficient co-delivery of combined therapeutic agents for combination anticancer therapy. This review focused on illustrating nanomedicine-based combination anticancer therapy between nucleic acids and small-molecular drugs for synergistically improving anticancer efficacy. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Comparison of the intraocular pressure-lowering effect and safety of brimonidine/timolol fixed combination and 0.5% timolol in normal-tension glaucoma patients.

    Science.gov (United States)

    Kim, Joon Mo; Kim, Tae-Woo; Kim, Chan Yun; Kim, Hwang Ki; Park, Ki Ho

    2016-01-01

    To compare the therapeutic efficacy and safety of brimonidine/timolol fixed-combination (BTFC) and 0.5% timolol ophthalmic solution in normal-tension glaucoma (NTG) patients. This was a multi-institution, randomized, active-controlled, open-label, parallel-group study. After a full ophthalmic and glaucoma examination, a total of 110 NTG patients--55 undergoing therapy with BTFC and 55 0.5%, with timolol--participated in this study. Among them, 1 failed to meet the inclusion/exclusion criteria, 10 revoked their consent to participate in the study, 3 had adverse reactions, and 1 had a drug adherence rate of less than 70%. Ultimately, a total of 95 patients--48 in the BTFC group and 47 in the 0.5% timolol group--completed the study. The study visits took place at baseline and at 4 and 12 weeks. Diurnal IOP was measured at 9 a.m., 11 a.m., and 5 p.m. during the baseline visit and the visit at 12 weeks after eye-drop instillation. At each follow-up visit, compliance was assessed. Throughout the study, all adverse events were recorded and monitored by the investigators. The average difference in IOP change measured at 11 a.m. 12 weeks after administration between the two groups was 2.10 ± 2.59 mmHg. The BTFC group had a better IOP-lowering effect at all time points than did the 0.5% timolol group. The ratio of patients whose average IOP had decreased by >20% after 4 and 12 weeks was 50 and 56% in the BTFC group, respectively, whereas it was 29.41 and 23.53% in the 0.5% timolol group, respectively (p = 0.034, <0.001). BTFC has a superior IOP-lowering effect than 0.5% timolol in NTG patients.

  19. The fixed combination of pioglitazone and metformin improves biomarkers of platelet function and chronic inflammation in type 2 diabetes patients: results from the PIOfix study.

    Science.gov (United States)

    Schöndorf, Thomas; Musholt, Petra B; Hohberg, Cloth; Forst, Thomas; Lehmann, Ute; Fuchs, Winfried; Löbig, Mirjam; Müller, Jürgen; Pfützner, Andreas

    2011-03-01

    Type 2 diabetes mellitus (T2DM) is characterized by a proinflammatory and procoagulant condition. This study investigates the impact of a pioglitazone plus metformin therapy on biomarkers of inflammation and platelet activation in comparison to a treatment with glimepiride plus metformin. The study was designed as a multicenter, randomized, double-blinded two-arm trial. Patients with T2DM and dyslipidemia under metformin monotherapy with hemoglobin A1c value between 6.5% and 9.0% were eligible for trial participation. Blood was drawn at baseline and after 24 weeks of treatment from patients of five centers. Markers of inflammation and thrombocyte function (soluble CD40 ligand, thromboxane, vWillebrand factor, adhesion molecules, clotting reaction) were evaluated subsequently in a central laboratory. A total of 46 patients were included in the final analyses. Mean (± standard deviation) age was 58.5 ± 9.0 years (13 women, 33 men; disease duration 6.3 ± 5.0 years; body mass index 32.0 ± 4.8 kg/m(2)). A total of 25 patients were treated with pioglitazone plus metformin, and 21 patients were in the glimepiride arm. There was a significant decline of E-selectin (-3.7 ± 4.8 ng/ml, p metformin + pioglitazone arm only (metformin + glimepiride, -0.5 ± 3.4 ng/ml, +1.4 ± 33.2%, + 0.08 ± 0.72 mg/liter, respectively, all not significant). Also, all other surrogate markers for platelet function and inflammation showed slight improvements in the metformin + pioglitazone arm but not in the metformin + glimepiride arm. The fixed metformin + pioglitazone combination treatment showed an overall improvement of laboratory surrogate markers, indicating improvement of platelet function and of chronic systemic inflammation, which was not seen with metformin + glimepiride. © 2011 Diabetes Technology Society.

  20. Antiplatelet Efficacy of Fixed-Dose Aspirin-Clopidogrel Combination in Patients with Stable Coronary Artery Disease Treated with Drug-Eluting Stent Implantation.

    Science.gov (United States)

    Lim, Sungmin; Kim, Pum Joon; Baek, Chunyeong; Kim, Tae-Hoon; Koh, Yoon Seok; Park, Hun-Jun; Kim, Hee-Yeol; Chang, Kiyuk; Chung, Wook Sung; Seung, Ki-Bae

    2015-12-01

    A fixed-dose combination (FDC) of aspirin and clopidogrel bisulfate may improve medication adherence. However, the absence of data on the relative antiplatelet efficacy of FDC and separate dual pills (SDP) of aspirin and clopidogrel in real-world patients with stable coronary artery disease is a major factor retarding clinical introduction of such an FDC. This was a single-centre, randomized, open-label, parallel-group, non-inferiority trial. Patients who maintained a regimen of separate aspirin and clopidogrel pills for at least 1 year after drug-eluting stent implantation without adverse events were enrolled. Patients were randomly assigned to either the FDC group or the SDP group. Antiplatelet efficacy and tolerability were assessed at baseline and at 4 weeks. Of the 93 enrolled patients, 83 (FDC group: n = 42; SDP group: n = 41) completed the study. The difference in the changes in P2Y12 percentage inhibition did not exceed the predetermined value for inferiority [mean difference -1.7; 95 % confidence interval (CI) -6.9 to 4.5, p aspirin reaction units (ARU) (mean difference -2.3 ARU, p = 0.88) did not differ significantly between the treatment groups. The tolerability of the FDC formulation was similar to that of SDP therapy (p = 0.68). In patients with prior percutaneous coronary intervention, the antiplatelet efficacy of the aspirin/clopidogrel FDC was non-inferior to that of SDP and the tolerability of the two regimens was similar after 4 weeks of treatment.

  1. The Cellient System for Paraffin Histology Can Be Combined with HPV Testing and Morphotyping the Vaginal Microbiome Thanks to BoonFixing

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    Mathilde E. Boon

    2013-01-01

    Full Text Available The Cellient Automated Cell Block System (Hologic can be used to process cervical scrapes to paraffin sections. For the first study on this subject, cervical scrapes were fixed in the formalin-free fixative BoonFix. This pilot study was limited to cases classified as atypical squamous lesion of unknown significance (ASCUS and high-grade squamous lesion (HSIL as diagnosed in the ThinPrep slide. The Cellient paraffin sections were classified into negative, atypical, CIN 1, CIN 2, and CIN 3. Multiple HPV genotypes were encountered in 79% of the scrapes. This study showed that the Cellient system for paraffin sections can be combined with HPV testing thanks to the formalin-free BoonFix. In two additional studies it was shown that such samples can also be used for morphotyping the vaginal microbiome and preparing cytologic ThinPrep slides.

  2. [Acupuncture combined with traction therapy for lumbar disc herniation: a systematic review].

    Science.gov (United States)

    Li, Xiu-zhen; Chen, Hai-yong; Zheng, Xiao; Liu, Nong-yu

    2014-09-01

    To evaluate the efficacy and safety of acupuncture combined with traction therapy for lumbar disc herniation, providing the basis for future research strategies. Randomized control trials. (RCT) of acupuncture combined with traction therapy for lumber disc herniation at home and abroad from 2000 to 2013 were searched, analysis and evaluation of literature and strength of evidence were based on the principles and methods of Evidence-based Medicine. The total effective rate and curative rate were considered as primary outcome measures; pain improvement, quality of life, relapse rate and adverse effects were considered as secondary outcome measures. Seventeen RCTs were identified, Meta-analysis showed that (1) total effective rate and curative rate: acupuncture combined with traction therapy was better than single therapy (acupuncture or traction); (2) pain improvement: acupuncture combined with traction therapy was better than traction therapy; (3) relapse rate: current evidence could not support the conclusion that acupuncture combined with traction therapy was better than traction therapy. Acupuncture combined with traction therapy for lumbar disc herniation was effective. However, the included studies were with high risk of bias, important outcome measures such as quality of life, relapse rate and adverse effects were not found in most of the studies. Current evidence has not yet been able to fully reflect acupuncture combined with traction therapy for lumbar disc herniation is better than single therapy, so more RCTs of higher quality are needed to further confirm its efficacy and safety.

  3. Reliability of using a fixed matrix in coregistration of combined PET–MRI in a split magnet design

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    Sawiak, S.J., E-mail: sjs80@cam.ac.uk [Behavioural and Clinical Neuroscience Institute, University of Cambridge, Downing Street, Cambridge CB2 3EB (United Kingdom); Wolfson Brain Imaging Centre, University of Cambridge, Cambridge CB2 0QQ (United Kingdom); Hawkes, R.C. [Wolfson Brain Imaging Centre, University of Cambridge, Cambridge CB2 0QQ (United Kingdom); Ansorge, R.E. [Department of Physics, University of Cambridge, Cambridge CB2 0QQ (United Kingdom); Carpenter, T.A. [Wolfson Brain Imaging Centre, University of Cambridge, Cambridge CB2 0QQ (United Kingdom)

    2013-02-21

    We consider the effects of using a fixed linear transformation to match positron emission tomography (PET) and magnetic resonance imaging (MRI) data acquired simultaneously using a split-magnet system. Estimates of the frequency offset in MRI scans were used to calculate geometric variability in MRI reconstruction as a consequence of mis-setting this parameter in addition to repeated estimation of the transformation matrix by manual measurements. None of the measured variability approached the resolution of the PET images, so we concluded that a fixed matrix can be reliably used in such a system.

  4. Asthma control in patients receiving inhaled corticosteroid and long-acting beta2-agonist fixed combinations. A real-life study comparing dry powder inhalers and a pressurized metered dose inhaler extrafine formulation

    Directory of Open Access Journals (Sweden)

    Nicolini Gabriele

    2011-07-01

    Full Text Available Abstract Background Although patients have more problems using metered dose inhalers, clinical comparisons suggest they provide similar control to dry powder inhalers. Using real-life situations this study was designed to evaluate asthma control in outpatients with moderate to severe persistent asthma and to compare efficacy of fixed combinations of inhaled corticosteroids (ICS and long acting beta-agonists (LABA. Methods This real-life study had a cross-sectional design. Patients using fixed combinations of ICS and LABA had their asthma control and spirometry assessed during regular visits. Results 111 patients were analyzed: 53 (47.7% received maintenance therapy of extrafine beclomethasone-formoterol (BDP/F pressurized metered dose inhaler (pMDI, 25 (22.5% fluticasone-salmeterol (FP/S dry powder inhaler (DPI, and 33 (29.7% budesonide-formoterol (BUD/F DPI. Severity of asthma at time of diagnosis, assessed by the treating physician, was comparable among groups. Asthma control was achieved by 45.9% of patients; 38.7% were partially controlled and 15.3% were uncontrolled. In the extrafine BDF/F group, asthma control total score, daytime symptom score and rescue medication use score were significantly better than those using fixed DPI combinations (5.8 ± 6.2 vs. 8.5 ± 6.8; 1.4 ± 1.8 vs. 2.3 ± 2.1; 1.8 ± 2.2 vs. 2.6 ± 2.2; p = 0.0160; p = 0.012 and p = 0.025, respectively and the mean daily ICS dose were significantly lower. Conclusions pMDI extrafine BDP/F combination demonstrated better asthma control compared to DPIs formulated with larger particles. This could be due to the improved lung deposition of the dose or less reliance on the optimal inhalation technique or both.

  5. Creative solutions to extraordinary challenges in clinical trials: methodology of a phase III trial of azithromycin and chloroquine fixed-dose combination in pregnant women in Africa.

    Science.gov (United States)

    Chandra, Richa S; Orazem, John; Ubben, David; Duparc, Stephan; Robbins, Jeffery; Vandenbroucke, Pol

    2013-04-11

    Malaria in pregnancy is one of the most common preventable causes of maternal and neonatal morbidity and mortality in sub-Saharan Africa. To prevent its adverse effects, such as maternal anaemia, placental parasitaemia and low birth weight (LBW) neonates, the World Health Organization recommends effective malaria case management, use of insecticide-treated bed nets and intermittent preventive therapy in pregnancy (IPTp). Sulphadoxine-pyrimethamine (SP) has been the standard for IPTp in several countries, but parasite resistance to SP is growing. Therefore, new IPTp therapies are urgently needed. One candidate being evaluated for IPTp is a fixed-dose combination of azithromycin and chloroquine (AZCQ). This paper describes the challenges and the innovative solutions implemented in designing and conducting a pivotal AZCQ-IPTp trial, sponsored by Pfizer Inc and co-funded by Pfizer Inc and the Medicines for Malaria Venture. The AZCQ-IPTp pivotal trial is a multicentre, multicountry, phase III, open-label, randomized superiority study of AZCQ-IPTp versus SP-IPTp in pregnant women of sub-Saharan Africa. The trial was designed to meet stringent regulatory agency scientific advice and IPTp policy makers' recommendations, and incorporates an innovative adaptive design to manage programme risk, maintain the operating characteristics of the study and optimize resources. The trial's novel composite primary endpoint is the proportion of participants with a suboptimal pregnancy outcome (abortion [≤28 weeks], stillbirths [>28 weeks], premature [data or loss to follow-up). The study employs a prospective group sequential design with three unblinded analyses when 50%, 70% and 100% of participants achieve the primary endpoint; the study team will remain blinded to the analyses until after the completion of the study. The number of participants randomized will be adaptive, based on the blinded review of the observed pooled primary endpoint data across the two treatment arms, when

  6. A case study of single-pill combination therapy: the ezetimibe/simvastatin combination for treatment of hyperlipidemia.

    Science.gov (United States)

    Huang, Xianhai; Chen, David Y-K

    2012-11-01

    In recent years, combination therapy has received growing popularity as a powerful therapeutic tactic for the treatment of diseases. The justifications and benefits of combination therapy are far-reaching, including but not limited to addressing unmet medical needs such as cancer, malaria, and HIV/AIDS, improved clinical efficacy and safety with reduced dosage of a single medication, understanding the underlying science of the disease, alleviating pharmaco-economic impacts, and better drug life-cycle management. Using the ezetimibe/simvastatin combination therapy as a case study, a comprehensive overview of the successful discovery and development of the single-pill combination, Vytorin, is presented in this review. A cursory introduction to combination therapy and the rationale for the ezetimibe/simvastatin combination for the treatment of hyperlipidemia provides an instructive entry point. The discovery and mode of action of simvastatin and ezetimibe monotherapies set the scene for a detailed discussion on the discovery and development of Vytorin, with emphasis on bioequivalency studies, clinical efficacy and safety profile studies, and the economic consequences of the single-pill combination therapy. Large-scale outcome clinical trials are also discussed to demonstrate the long-term effects of Vytorin. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Efficacy and safety of tigecycline monotherapy versus combination therapy for the treatment of hospital-acquired pneumonia (HAP): a meta-analysis of cohort studies.

    Science.gov (United States)

    Bai, Xiang-Rong; Liu, Jia-Ming; Jiang, De-Chun; Yan, Su-Ying

    2018-02-06

    The broad spectrum antibiotic tigecycline shows promising efficacy against many multiple drug resistant (MDR) pathogens. However, its clinical efficacy in the treatment of hospital-acquired pneumonia (HAP) is unclear. Several studies have reported on the treatment failures of tigecycline monotherapy, suggesting that it may not be sufficient to control severe infections. Combination therapy has become an option to treat MDR bacterial infections. We conducted a literature search using PubMed, Cochrane Library, Embase, Elsevier and the Web of Knowledge databases up to 29 February 2017 to identify relevant published studies. Studies were considered eligible if they were a cohort study that assessed mortality and the safety of tigecycline monotherapy versus combination therapy with other antimicrobial agents for HAP. The primary outcome was treatment mortality rate, while the secondary outcomes were adverse events. Meta-analysis was done using fixed-effects models. Five trials were included. The monotherapy tigecycline had a higher mortality compared to the combination therapy group. There was a significant difference for the treatment of HAP. However, two prospective cohort studies showed that there was no significant difference in mortality rate between the tigecycline monotherapy and the tigecycline combination therapy. Three retrospective cohort studies showed that tigecycline monotherapy had a high mortality rate. Tigecycline combination therapy efficiently treats HAP. There is a great need for well-designed studies to evaluate the effectiveness and safety of combination therapies as they compare to tigecycline monotherapy.

  8. PATHOGENETIC RATIONALE FOR COMBINATION THERAPY OF PATIENTS WITH CHRONIC PANCREATITIS

    Directory of Open Access Journals (Sweden)

    V. B. Grinevich

    2015-01-01

    Full Text Available Background: Chronic pancreatitis is characterized by an imbalance of pro-inflammatory and anti-inflammatory cytokines, reflecting the presence of chronic systemic inflammation. The functional state of microbial-tissue complex of the intestine determines the severity of chronic systemic inflammation. Restoration of normal microbial-tissue complex functioning of the intestine reduces the severity of inflammatory changes in the pancreas.Aim: To study clinical efficacy of combination of chronic pancreatitis through correction of the functional state of intestinal microbial-tissue complex.Materials and methods: The analyzed patient sample included 117 patients with uncomplicated chronic pancreatitis and moderate pain syndrome, moderate exocrine and endocrine, with their mean age of 43.9 ± 11.6 years (men, 40.9 ± 13.5 years and women, 48.6 ± 11.7 years. Patients with chronic pancreatitis were divided into 2 groups, with the Results: After combination therapy of chronic pancreatitis with the agent for correction of the functional state of intestinal microbial-tissue complex, there was a significant (p < 0.05 reduction in the representation of pathogenic and conditionally pathogenic microflora, with a significant increase in the primary intestinal flora, as well as a decrease in cytokines TNF-α (74.32 ± 11.22 ng/ml before treatment, 31.34 ± 8.92 ng/ml after treatment and IL-1β (25.32 ± 4.36 ng/ml before treatment, 10.52 ± 3.52 ng/ml after treatment, a significant decrease in cortisol (456.53 ± 68.99 nmol/ml before treatment, 382.61 ± 60.24 nmol/ml after treatment. The significant improvement of metabolic abnormalities was associated with positive clinical dynamics and improvement of quality of life.Conclusion: Treatment strategies in chronic pancreatitis should include agents restoring the functioning of intestinal microbial-tissue complex and positively affecting metabolic and hormonal milieu.

  9. Combination Therapy for Treatment of Infections with Gram-Negative Bacteria

    Science.gov (United States)

    Cosgrove, Sara E.; Maragakis, Lisa L.

    2012-01-01

    Summary: Combination antibiotic therapy for invasive infections with Gram-negative bacteria is employed in many health care facilities, especially for certain subgroups of patients, including those with neutropenia, those with infections caused by Pseudomonas aeruginosa, those with ventilator-associated pneumonia, and the severely ill. An argument can be made for empiric combination therapy, as we are witnessing a rise in infections caused by multidrug-resistant Gram-negative organisms. The wisdom of continued combination therapy after an organism is isolated and antimicrobial susceptibility data are known, however, is more controversial. The available evidence suggests that the greatest benefit of combination antibiotic therapy stems from the increased likelihood of choosing an effective agent during empiric therapy, rather than exploitation of in vitro synergy or the prevention of resistance during definitive treatment. In this review, we summarize the available data comparing monotherapy versus combination antimicrobial therapy for the treatment of infections with Gram-negative bacteria. PMID:22763634

  10. ENDOTHELIAL-TROPIC AND NEPHROPROTECTIVE EFFECTS OF COMBINED ANTIHYPERTENSIVE THERAPY IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

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    M. E. Statsenko

    2014-01-01

    Full Text Available Aim. To assess the effect of the 24-week antihypertensive therapy with fixed-dose drug combination (lisinopril plus amlodipine on endothelial dysfunction and renal function in patients with arterial hypertension (HT and diabetes mellitus (DM type 2.Material and methods. 30 hypertensive patients with DM type 2 (aged 40-65 years were included into the study. Endothelial function (plasma and vascular components and renal function were studied.Results. Combined antihypertensive therapy significantly improved parameters of endothelial function in patients with HT and DM type 2: production of nitric oxide (NO in blood serum and urine increased by 122.8% and 65.8%, respectively. Along with these secretion of endothelin (ET-1 in serum and urine decreased by 26.1% and by 76.1%, respectively, p<0.05. A statistically significant redistribution of patients by type of microcirculation was established: the share of patients with normal type of microcirculation increased by 73.4%. There was a statistically significant reduction of proteinuria and albuminuria by 58% and 43.6%, respectively. The share of patients with chronic kidney disease with an estimated GFR 30-60 ml/min/1.73 m2 decreased by 16.7%.Conclusions. It has been shown that the prescription of a long-term antihypertensive therapy with dose-fixed combination (lisinopril plus amlodipine is safe and effective for endothelial function improvement, including renal endothelium, with no negative effect on glucose and lipid metabolism in patients with HT and DM type 2.

  11. Minimally invasive local ablative therapies in combination with radioiodine therapy in benign thyroid disease: preparation, feasibility and efficiency - preliminary results.

    Science.gov (United States)

    Mader, Alexander; Mader, Oscar Maximilian; Gröner, Daniel; Korkusuz, Yücel; Ahmad, Shadi; Grünwald, Frank; Kranert, W Tilman; Happel, Christian

    2017-12-01

    Initial studies of combinations of radioiodine therapy (RIT) and local ablative procedures for the treatment of thyroid nodules have shown promising results. The goal of this study was to evaluate the effectiveness of RIT combined with radiofrequency ablation (RFA) in patients with goitres and to determine which ablative procedure is the most suitable for a combined therapy. Thirty patients with goitres were divided into two subgroups. A test group of 15 patients received combined therapy (RIT + RFA) and a control group of 15 patients received RIT mono therapy. All patients underwent assessments including ultrasound, laboratory evaluation (T3, T4, TSH, TG, TPOAb, TgAbTRAb) and scintigraphic imaging with Tc-99m-Pertechnetate. The 3-month volume reduction was used to evaluate therapy effectiveness. Combined therapy (subgroup 1) resulted in a significant (p  0.05) than the control group (20.2 ± 32.2 ml/29.6 ± 42.1%). All patients became euthyroid after treatment. No major discomfort or complications occurred. A review of the literature investigating combinations of other local ablative procedures with RIT was performed to determine the most promising combination. The present study confirms the positive experiences with the combined therapy of RIT and local ablative procedures shown in the current literature and approves this approach for the treatment of goitres with RFA + RIT. These findings, when confirmed by further studies, should expand the indication of combined therapy as a minimally invasive alternative to surgery.

  12. Hybrid drug combination: Combination of ferulic acid and metformin as anti-diabetic therapy.

    Science.gov (United States)

    Nankar, Rakesh; Prabhakar, P K; Doble, Mukesh

    2017-12-15

    Ferulic acid, an anti-oxidant phytochemical present in several dietary components, is known to produce wide range of pharmacological effects. It is approved for use in food industry as a preservative and in sports food. Previous reports from our lab have shown synergistic interaction of ferulic acid with metformin in cell lines and diabetic rats. The purpose of this review is to compile information about anti-diabetic activity of ferulic acid in in vitro and in vivo models with special emphasis on activity of ferulic acid when combined with metformin. The mechanism of synergistic interaction between ferulic acid and metformin is also proposed after carefully studying effects of these compounds on molecules involved in glucose metabolism. Scientific literature for the purpose of this review was collected using online search engines and databases such as ScienceDirect, Scopus, PubMed and Google scholar. Ferulic acid forms resonance stabilized phenoxyl radical which scavenges free radicals and reduce oxidative stress. It improves glucose and lipid profile in diabetic rats by enhancing activities of antioxidant enzymes, superoxide dismutase and catalase in the pancreatic tissue. Combining ferulic acid with metformin improves both, in vitro glucose uptake activity and in vivo hypoglycemic activity of the latter. It is possible to reduce the dose of metformin by four folds (from 50 to 12.5 mg/kg body weight) by combining it with 10 mg of ferulic acid/kg body weight in diabetic rats. Ferulic acid improves glucose uptake through PI3-K pathway whereas metformin activates AMPK pathway to improve glucose uptake. The synergistic interaction of ferulic acid and metformin is due their action on parallel pathways which are involved in glucose uptake. Due to synergistic nature of their interaction, it is possible to reduce the dose of metformin (by combining with ferulic acid) required to achieve normoglycemia. Since the dose of metformin is reduced, the dose associated side

  13. In vivo determination of tooth mobility after fixed orthodontic appliance therapy with a novel intraoral measurement device.

    Science.gov (United States)

    Konermann, Anna; Al-Malat, R; Skupin, J; Keilig, L; Dirk, C; Karanis, R; Bourauel, C; Jäger, A

    2017-05-01

    Valid measurement systems recording tooth mobility upon displacement within the subtle range of physiological strains are missing. Here, we introduce a novel in vivo measurement device and demonstrate a first clinical application by monitoring tooth mobility changes during retention after fixed multibracket appliance therapy. Tooth mobility was measured in vivo on 21 patients (11 female, 10 male; mean age 16.1 ± 3.1 years) by displacing the upper first incisor 0.2 mm lingually for 0.2, 0.5, 1, 2, 5, and 10 s with the novel intraoral device. Measurements were recorded directly after, as much as 2, 7, and 14 days and up to 6 months after appliance debonding. Device performance was precise and valid in clinical use. Data revealed significant interindividual varying tooth mobility, which was very high during the first 2 days after appliance removal. After 1 week, mobility values decreased, but were generally higher upon short loadings compared to long ones. After 3 months, tooth mobility was significantly lower than directly after debonding. Interestingly, males exhibited significantly less mobility than females. Our work is the first using an in vivo measurement device capable of performing and recording tooth displacements within this delicate range and in such precision. Furthermore, our findings elucidate tooth mobility changes after multibracket treatment, giving important information for retention periods. Establishment of this novel measurement device in clinical use is an important improvement when approaching the complexity of tooth mobility in vivo regarding different issues like orthodontics, periodontal disease, or bruxism.

  14. Preliminary results following the use of a fixed combination of timolol–brimonidine in patients with ocular hypertension and primary open-angle glaucoma

    Directory of Open Access Journals (Sweden)

    Dimitris Papaconstantinou

    2009-03-01

    Full Text Available Dimitris Papaconstantinou1, Ilias Georgalas2, Nikolaos Kourtis1, Christos Pitsas1, Efthimios Karmiris1, Chrysanthi Koutsandrea1, Ioannis Ladas1, Gerasimos Georgopoulos11Department of Ophthalmology, “G Gennimatas” Hospital of Athens, University of Athens, Athens, Greece; 2Department of Ophthalmology, “G Gennimatas” Hospital of Athens, NHS, Athens, Greece Purpose: The purpose of this prospective study was to evaluate the efficacy in intraocular pressure (IOP control and the tolerance of a topically administered fixed combination of timolol–brimonidine in 50 patients with ocular hypertension and primary open-angle glaucoma.Methods: After determining a baseline IOP, the fixed combination timolol–brimonidine was used twice daily for two months, while IOP, ophthalmic signs, and/or symptoms were monitored.Results: The mean IOP value was decreased from 23.09 mm Hg (±1.98 SD to 17.46 mm Hg (±1.47 SD during the 1st month (paired Student’s t test = 9.88 και p < 0.001, and to 17.51 mm Hg (±1.43 SD in the 2nd month. Between the 1st and 2nd month, no statistical difference was observed (paired Student’s t test = 0.02 και p < 0.1. In 8% of the patients during the 1st month and 10% of patients in the 2nd month, some ophthalmic signs were observed, while only mild ophthalmic symptoms were reported in 6% and 8% of the patients, respectively.Conclusions: In conclusion, the fixed combination of timolol–brimonidine has a satisfactory IOP-lowering effect without any serious side effects due to the topical use. Keywords: fixed combination 0.2% brimonidine–0.5% timolol, ocular hypertension, primary open-angle glaucoma

  15. Health outcome and safety assessment of a fixed dose combination of Amantadine, Paracetamol, Chlorpheniramine maleate, and Phenylephrine introduction in India: A prescription event monitoring study

    OpenAIRE

    Krishnaprasad, K.; Manshani, P.; Karankumar, J.

    2012-01-01

    To assess the likely impact of a fixed dose combination (FDC) of Amantadine, Paracetamol, Chlorpheniramine maleate, and Phenylephrine on the health outcome and safety profile arising from the complementary action of amantadine and other ingredients, we conducted a Prescription Event Monitoring study for patients with suspected Influenza symptoms who were prescribed this FDC in ′real life clinical settings′ or clinical practice. Between August 2010 and March 2011, Questionnaires were sent to d...

  16. Effectiveness of RHZE-FDC (fixed-dose combination) compared to RH-FDC?+?Z for tuberculosis treatment in Brazil: a cohort study

    OpenAIRE

    Braga, Jos? Ueleres; Trajman, Anete

    2015-01-01

    Background In 2009, Brazil was the sole high-burden country to use three drugs [rifampin (R), isoniazid (H) and pyrazinamide (Z)] as the standard treatment for sensitive tuberculosis, with RH in fixed-dose combination (FDC). In December 2009, the country has adopted the FDC four-drug regimen including ethambutol (E). The rationale was the expectation to reduce default and resistance rates, by increasing adherence to treatment and avoiding monotherapy. However, there is no consensus on the sup...

  17. Cost analysis of HIV treatment and drug-related adverse events when fixed-dose combinations of antiretrovirals (FDCs) were stopped, versus continuation with FDCs

    OpenAIRE

    Homar, Francesc; Lozano, Virginia; Martínez-Gómez, Juan; Oyagüez, Itziar; Pareja, Antonio; Payeras, Antoni; Serrano, Joaquín; Carratalá, Carmen; Casado, Miguel Ángel

    2012-01-01

    Background: The lower sales price of generic lamivudine has caused healthcare administrators to consider abolishing fixed-dose antiretroviral combinations (FDCs) that contain lamivudine and emtricitabine. The alternative is to administer the individual components of the FDCs separately, thus incorporating the new generic lamivudine medication. Methods: The Balearic Islands Health Service ordered the discontinuation of the treatment with FDCs in July 2010, but FDCs were reintroduced in August ...

  18. Efficacy and safety of brinzolamide/timolol fixed combination compared with timolol in Japanese patients with open-angle glaucoma or ocular hypertension [Erratum

    Directory of Open Access Journals (Sweden)

    Yoshikawa K

    2014-05-01

    Full Text Available  Yoshikawa K, Kozaki J, Maeda H. Efficacy and safety of brinzolamide/timolol fixed combination compared with timolol in Japanese patients with open-angle glaucoma or ocular hypertension. Clin Ophthalmol. 2014;8:389–399.The Acknowledgments on page 397 contains an error: "Hidehito Kawabata (Kusakari Eye Clinic, Chiba, Japan" should be "Hidehito Kawabata (Kawabata Eye Clinic, Chiba, Japan".Read the original article

  19. Reconstruction of the Shallow Acetabulum With a Combination of Autologous Bulk and Impaction Bone Grafting Fixed by Cement.

    Science.gov (United States)

    Maruyama, Masaaki; Wakabayashi, Shinji; Ota, Hiroshi; Tensho, Keiji

    2017-02-01

    Acetabular bone deficiency, especially proximal and lateral deficiency, is a difficult technical problem during primary total hip arthroplasty (THA) in developmental dysplasia of the hip (DDH). We report a new reconstruction method using a medial-reduced cemented socket and additional bulk bone in conjunction with impaction morselized bone grafting (additional bulk bone grafting method). In a population of patients with acetabular dysplasia undergoing THA using a medial-reduced cemented socket and additional bulk bone with impacted morselized bone grafting, we evaluated (1) the radiographic appearance of bone graft; (2) the proportion of cups that developed loosening and subsequent revision; and (3) clinical results (outcome scores and complications). Forty percent of 330 THAs for DDH performed at one center between 1999 and 2009 were defined as shallow dysplastic hips. The additional bulk bone grafting method was performed on 102 THAs with shallow acetabulum (31% for DDH) at one center between 1999 and 2009. We used this approach and technique for shallow acetabuli when a cup protruded from the lateral acetabular edge in preoperative templating. The other 132 dysplastic hips without bone grafting had THA performed at the same periods and served as a control. Acetabuli were defined as shallow when the depth was less than or equal to one-fifth of the pelvic height (cranial-caudal length on radiograph). The additional bulk bone grafting technique was as follows: the resected femoral head was sectioned at 1 to 2 cm thickness, and a suitable size of the bulk bone graft was placed on the lateral iliac cortex and fixed by poly-L-lactate absorbable screws. Autologous impaction morselized bone grafting, with or without hydroxyapatite granules, was performed along with the implantation of a medial-reduced cemented socket. We defined an "incorporated" graft as remodeling and trabeculation including rounding off of the protruding edge of a graft beyond the socket

  20. Discordant perspectives of rheumatologists and patients on COBRA combination therapy in rheumatoid arthritis.

    NARCIS (Netherlands)

    Tuyl, L.H.D. van; Plass, A.M.C.; Lems, W.F.; Voskuyl, A.E.; Kerstens, P.J.S.M.; Dijkmans, B.A.C.; Boers, M.

    2008-01-01

    Objective. The COBRA therapy (combination therapy in early rheumatoid arthritis) has proven to be an effective treatment for early RA, but is rarely prescribed. A survey showed reluctance of Dutch reumatologists to apply COBRA therapy in early RA. The present qualitative study was carried out to

  1. Discordant perspectives of rheumatologists and patients on COBRA combination therapy in rheumatoid arthritis

    NARCIS (Netherlands)

    van Tuyl, L.H.D.; Plass, A.M.C.; Lems, W.F.; Voskuyl, A.E.; Kerstens, P.J.S.M.; Dijkmans, B.A.C.; Boers, M.

    2008-01-01

    Objective. The COBRA therapy (combination therapy in early rheumatoid arthritis) has proven to be an effective treatment for early RA, but is rarely prescribed. A survey showed reluctance of Dutch reumatologists to apply COBRA therapy in early RA. The present qualitative study was carried out to

  2. PROTON THERAPY IN COMBINATION WITH PET AS MONITOR - A FEASIBILITY STUDY

    NARCIS (Netherlands)

    PAANS, AMJ; SCHIPPERS, JM

    To evaluate the possibility of combining proton therapy with Positron Emission Tomography (PET) as a therapy monitor and as a tool for in situ dosimetry during therapy, proton activiation experiments have been performed using a 55 MeV proton beam on two different materials. The 3-D measurements of

  3. Combination therapy for pain management in inflammatory arthritis (rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, other spondyloarthritis)

    NARCIS (Netherlands)

    Ramiro, Sofia; Radner, Helga; van der Heijde, Désirée; van Tubergen, Astrid; Buchbinder, Rachelle; Aletaha, Daniel; Landewé, Robert B. M.

    2011-01-01

    Despite optimal therapy with disease-modifying antirheumatic drugs, many people with inflammatory arthritis (IA) continue to have persistent pain that may require additional therapy. To assess the benefits and safety of combination pain therapy for people with IA (rheumatoid arthritis (RA),

  4. A Randomized Controlled Trial of Cognitive-Behavioral Therapy, Light Therapy, and Their Combination for Seasonal Affective Disorder

    Science.gov (United States)

    Rohan, Kelly J.; Roecklein, Kathryn A.; Tierney Lindsey, Kathryn; Johnson, Leigh G.; Lippy, Robert D.; Lacy, Timothy J.; Barton, Franca B.

    2007-01-01

    This first controlled psychotherapy trial for seasonal affective disorder (SAD) compared SAD-tailored cognitive-behavioral therapy (CBT), light therapy (LT), and their combination to a concurrent wait-list control. Adults (N = 61) with major depression, recurrent with seasonal pattern, were randomized to one of four 6-week conditions: CBT (1.5-hr…

  5. Combination therapy of intravitreal triamcinolone and photodynamic therapy with verteporfin for subfoveal choroidal neovascularization

    Directory of Open Access Journals (Sweden)

    Hussain Nazimul

    2006-01-01

    Full Text Available Aim: To evaluate the six months follow-up outcome of combined intravitreal triamcinolone acetonide (IVTA and photodynamic therapy (PDT for subfoveal choroidal neovascularization compared to PDT alone. Study design: Prospective interventional pilot study. Materials and Methods: Patients with six months follow-up of IVTA following PDT (Group I, eight eyes and PDT alone (Group II, eight eyes were included. Four mg/ 0.1 ml of IVTA was injected 7-10 days following PDT. The patients were reevaluated every month for the first two months and every three months thereafter in both the groups. Results: Group I: The mean age was 65.8±11.8 years (range: 47-79 years. Five patients were male. The total treatment sessions in six months were 11 (mean: 1.36. At six months, one eye had ³ 10 letters gain and three eyes had > 10 letters loss. Four eyes had stable vision. Two eyes (25% developed increased intraocular pressure (>40 mmHg during follow-up. Group II: The mean age was 58.7±11.7 years (range: 46-76 years. Five patients were male. The total treatment sessions in six months were 17 (mean: 2.13. At six months, six eyes had ³ 10 letters gain and none had > 10 letters loss. Two eyes had stable vision. Conclusion: The mean number of treatment sessions following combination therapy of IVTA (4 mg and PDT appears relatively less (1.36 at six months compared to PDT alone (mean: 2.13. ( P =0.02

  6. Aldosterone breakthrough during aliskiren, valsartan, and combination (aliskiren + valsartan) therapy.

    Science.gov (United States)

    Bomback, Andrew S; Rekhtman, Yelena; Klemmer, Philip J; Canetta, Pietro A; Radhakrishnan, Jai; Appel, Gerald B

    2012-01-01

    Aldosterone levels increase in 30%-40% of patients on angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers over the long term. This "aldosterone breakthrough" may carry important clinical consequences given aldosterone's nonepithelial, pro-fibrotic actions. The renin inhibitor, aliskiren, by suppressing the renin-angiotensin-aldosterone system (RAAS) proximally, may limit breakthrough compared to conventional RAAS blockade. This open-label study (NCT01129557) randomized subjects to aliskiren 300 mg daily (A), valsartan 320 mg daily (V), or aliskiren 150 mg + valsartan 160 mg daily (A+V) for 9 months. Eligible subjects had proteinuria >300 mg/day, estimated glomerular filtration rate (eGFR) >45 mL/min/1.73 m(2), and systolic blood pressure (BP) >130 or diastolic BP >80 mm Hg. Serum and 24-hour urine aldosterone (indexed to 24-hour urine Na) were checked before initiation of therapy and at 3, 6, and 9 months. Aldosterone breakthrough was defined as a sustained increase from baseline aldosterone by study end. The study was intended to enroll 120 subjects but was terminated early by the sponsor. We present here the results of 33 subjects who completed the protocol, of which 12 were randomized to A, 11 were randomized to V, and 10 were randomized to A+V. Mean baseline eGFR was 75.5 (±23.3) mL/min/1.73 m(2); baseline proteinuria was 3104 (±2943) mg/day; and baseline BP was 134.7 (±10.5)/84.8 (±8.4) mm Hg. Three (27%) subjects on V, three (25%) subjects on A, and three (30%) subjects on A+V had aldosterone breakthrough. Mean proteinuria reduction was 31% from baseline in all subjects: 30% in subjects with breakthrough vs. 32% in subjects without breakthrough. Mean BP reduction was 11.0/8.8 mm Hg in all subjects: 8.4/6.1 mm Hg in subjects with breakthrough vs. 12.0/9.8 mm Hg in subjects without breakthrough. Aliskiren, alone or in combination with valsartan, did not reduce the incidence of aldosterone breakthrough in subjects with hypertension

  7. Changes in Cognitive-Behavioral Constructs Across Treatment Modalities for Seasonal Affective Disorder: Cognitive-Behavioral Therapy, Light Therapy, and their Combination"

    Science.gov (United States)

    2003-01-01

    Cognitive - Behavioral Therapy , Light Therapy , and their Combination” Name of Candidate: Kathryn Tierney Lindsey Master of Science Degree...Changes in Cognitive - Behavioral Constructs Across Treatment Modalities for Seasonal Affective Disorder: Cognitive - Behavioral Therapy , Light Therapy ...assigned to light therapy (LT), group cognitive - behavioral therapy (CBT), or a combination treatment (CBT+LT). Participants completed

  8. Fixed-Combination Gels of Adapalene and Benzoyl Peroxide Provide Optimal Percutaneous Absorption Compared to Monad Formulations of These Compounds: Results from Two In Vitro Studies

    OpenAIRE

    Osman-Ponchet, Hanan; Sevin, Karine; Gaborit, Alexandre; Wagner, Nathalie; Poncet, Michel

    2016-01-01

    Introduction Adapalene 0.1%/benzoyl peroxide 2.5% (0.1% A/BPO) and adapalene 0.3%/BPO 2.5% (0.3% A/BPO) gels are fixed-combination options for the topical treatment of acne. However, the active compounds of these combinations are also available as monads, to be used in association or as monotherapy. These two in vitro studies determined the effect of different treatment regimens on the percutaneous absorption of adapalene (0.1% and 0.3%) gels and BPO 2.5% gel in ex vivo human skin. Methods In...

  9. Investigation of bioequivalence of a new fixed-dose combination of acarbose and metformin with the corresponding loose combination as well as the drug-drug interaction potential between both drugs in healthy adult male subjects.

    Science.gov (United States)

    Kim, S; Jang, I-J; Shin, D; Shin, D S; Yoon, S; Lim, K S; Yu, K-S; Li, J; Zhang, H; Liu, Y; Brendel, E; Blode, H; Wang, Y

    2014-08-01

    Both metformin and acarbose are recommended monotherapy and add-on therapy in type 2 diabetes mellitus (T2DM). A fixed-dose combination (FDC) of acarbose and metformin has been developed to reduce pill burden and potentially improve compliance. The current study investigated the bioequivalence of the acarbose/metformin FDC compared with the individual agents administered simultaneously (loose combination). Secondary endpoints were the safety and tolerability of the FDC and the potential for drug-drug interactions between acarbose and metformin. A single-centre, randomized, open-label, four-period crossover study was conducted in healthy male Korean subjects aged 18-45 years. Following one-period balanced Williams design, participants were randomized to receive four single oral treatments on different study days separated by ≥7 days' washout. Treatments were as follows: (i) acarbose/metformin 50/500 mg FDC (test); (ii) acarbose 50 mg and metformin 500 mg as loose combination (reference); (iii) acarbose 50 mg; and (iv) metformin 500 mg. Serial blood samples were taken for glucose and insulin levels for 4 h after a sucrose load on the day before and day of study drug administration. Additionally, serial blood samples were taken for analysis of metformin levels for 24 h after each drug containing metformin. The area under the curve for 4 h post-test (AUC0-4 h ) and the maximal serum concentration (Cmax ) of plasma glucose and serum insulin were primary pharmacodynamic (PD) parameters, and Cmax , AUC0-last and AUC for metformin levels were primary pharmacokinetic (PK) parameters. The bioequivalence of the FDC to the loose combination was considered established if the 90% confidence intervals (CIs) of the baseline-adjusted PD parameter ratios (test vs. reference) for plasma glucose and the PK parameter ratios for metformin fell completely within current acceptance limits (0·8-1·25). Thirty-three of 40 randomized subjects completed the study; five withdrew

  10. Effectiveness of cognitive behavioral therapy integrated with systematic desensitization, cognitive behavioral therapy combined with eye movement desensitization and reprocessing therapy, and cognitive behavioral therapy combined with virtual reality exposure therapy methods in the treatment of flight anxiety: a randomized trial.

    Science.gov (United States)

    Triscari, Maria Teresa; Faraci, Palmira; Catalisano, Dario; D'Angelo, Valerio; Urso, Viviana

    2015-01-01

    The purpose of the research was to compare the effectiveness of the following treatment methods for fear of flying: cognitive behavioral therapy (CBT) integrated with systematic desensitization, CBT combined with eye movement desensitization and reprocessing therapy, and CBT combined with virtual reality exposure therapy. Overall, our findings have proven the efficacy of all interventions in reducing fear of flying in a pre- to post-treatment comparison. All groups showed a decrease in flight anxiety, suggesting the efficiency of all three treatments in reducing self-report measures of fear of flying. In particular, our results indicated significant improvements for the treated patients using all the treatment programs, as shown not only by test scores but also by participation in the post-treatment flight. Nevertheless, outcome measures maintained a significant effect at a 1-year follow-up. In conclusion, combining CBT with both the application of eye movement desensitization and reprocessing treatment and the virtual stimuli used to expose patients with aerophobia seemed as efficient as traditional cognitive behavioral treatments integrated with systematic desensitization.

  11. 5-Aminolevulinic Acid Photodynamic Therapy combined with CO2 laser therapy in treatment of laryngeal papilloma: Case report.

    Science.gov (United States)

    Zhang, Yunjie; Yang, Yuguang; Zou, Xianbiao; Huang, Zheng

    2016-06-01

    This article describes the case of 5-Aminolevulinic Acid Photodynamic Therapy (ALA-PDT) via self-retaining laryngoscope under general anesthesia combined with CO2 Laser Therapy in the treatment of three patients with juvenile laryngeal papilloma. Laryngeal papilloma Clinically, it features rapid growth, multi-focus, frequent recurrence and possibility of spreading to the lower respiratory tract. ALA-PDT via self-retaining laryngoscope under general anesthesia combined with CO2 Laser Therapy is safe and effective for clearing laryngeal papilloma, laryngeal papilloma was fully removed from the three patients, with no recurrence during the 6-24 months of follow-up medical examination. 5-Aminolevulinic Acid Photodynamic Therapy (ALA-PDT) via self-retaining laryngoscope under general anesthesia combined with CO2 Laser can be used for treating laryngeal papilloma. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Impact of combined clenbuterol and metoprolol therapy on reverse remodelling during mechanical unloading.

    Directory of Open Access Journals (Sweden)

    Manoraj Navaratnarajah

    Full Text Available Clenbuterol (Cl, a β2 agonist, is associated with enhanced myocardial recovery during left ventricular assist device (LVAD support, and exerts beneficial remodelling effects during mechanical unloading (MU in rodent heart failure (HF. However, the specific effects of combined Cl+β1 blockade during MU are unknown.We studied the chronic effects (4 weeks of β2-adrenoceptor (AR stimulation via Cl (2 mg/kg/day alone, and in combination with β1-AR blockade using metoprolol ((Met, 250 mg/kg/day, on whole heart/cell structure, function and excitation-contraction (EC coupling in failing (induced by left coronary artery (LCA ligation, and unloaded (induced by heterotopic abdominal heart transplantation (HATx failing rat hearts. Combined Cl+Met therapy displayed favourable effects in HF: Met enhanced Cl's improvement in ejection fraction (EF whilst preventing Cl-induced hypertrophy and tachycardia. During MU combined therapy was less beneficial than either mono-therapy. Met, not Cl, prevented MU-induced myocardial atrophy, with increased atrophy occurring during combined therapy. MU-induced recovery of Ca2+ transient amplitude, speed of Ca2+ release and sarcoplasmic reticulum Ca2+ content was enhanced equally by Cl or Met mono-therapy, but these benefits, together with Cl's enhancement of sarcomeric contraction speed, and MU-induced recovery of Ca2+ spark frequency, disappeared during combined therapy.Combined Cl+Met therapy shows superior functional effects to mono-therapy in rodent HF, but appears inferior to either mono-therapy in enhancing MU-induced recovery of EC coupling. These results suggest that combined β2-AR simulation +β1-AR blockade therapy is likely to be a safe and beneficial therapeutic HF strategy, but is not as effective as mono-therapy in enhancing myocardial recovery during LVAD support.

  13. Combined estrogen replacement therapy on metabolic control in postmenopausal women with diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Youhua Xu

    2014-07-01

    Full Text Available Previous studies have shown that the incidence of diabetes is higher when women come to menopause. This study was carried out to examine the effects of combined estrogen replacement therapy (ERT on diabetes in postmenopausal women. PubMed/MEDLINE was searched for English-language articles published between January 1997 and June 2011. Studies that examined ERT on the incidence of diabetes and randomized clinical trials that evaluated combined ERT (estrogen plus progesterone on diabetic indices in postmenopausal women were included. Pooled relative risks were calculated using a random- or a fixed-effects model. Sixteen studies comprising 17,971 cases were included. Based on the pooled data, ERT significantly reduced the incidence of diabetes [odds ratio (OR, 0.61; 95% confidence interval (CI, 0.55–0.68, ERT past/current/continuous use vs. never use; OR, 0.57; 95% CI, 0.51–0.65, ERT current/continuous use vs. past/never use]. Women with combined ERT have significantly lower levels of fasting plasma glucose (mean difference, –1.41 mM/L; 95% CI, –2.49 to −0.33 mM/L and HbA1c (mean difference, –0.73%; 95% CI, from −1.28 to −0.18% compared with placebo. Furthermore, combined ERT dramatically reduced plasma total cholesterol (mean difference, –0.34 mM/L; 95% CI, from −0.53 to −0.15 mM/L and low-density lipoprotein (mean difference, –0.43 mM/L; 95% CI, from −0.71 to −0.14 mM/L but slightly increased high-density lipoprotein (mean difference, 0.02 mM/L; 95% CI, from −0.07 to 0.12 mM/L levels as compared with placebo control. This systemic review and meta-analysis provides evidence that postmenopausal women taking low-dose combined ERT have a decreased risk of developing diabetes and have better diabetic control.

  14. Whole abdomen radiation therapy in ovarian cancers: a comparison between fixed beam and volumetric arc based intensity modulation

    Directory of Open Access Journals (Sweden)

    Clivio Alessandro

    2010-11-01

    Full Text Available Abstract Purpose A study was performed to assess dosimetric characteristics of volumetric modulated arcs (RapidArc, RA and fixed field intensity modulated therapy (IMRT for Whole Abdomen Radiotherapy (WAR after ovarian cancer. Methods and Materials Plans for IMRT and RA were optimised for 5 patients prescribing 25 Gy to the whole abdomen (PTV_WAR and 45 Gy to the pelvis and pelvic nodes (PTV_Pelvis with Simultaneous Integrated Boost (SIB technique. Plans were investigated for 6 MV (RA6, IMRT6 and 15 MV (RA15, IMRT15 photons. Objectives were: for both PTVs V90% > 95%, for PTV_Pelvis: Dmax Results IMRT and RapidArc resulted comparable for target coverage. For PTV_WAR, V90% was 99.8 ± 0.2% and 93.4 ± 7.3% for IMRT6 and IMRT15, and 98.4 ± 1.7 and 98.6 ± 0.9% for RA6 and RA15. Target coverage resulted improved for PTV_Pelvis. Dose homogeneity resulted slightly improved by RA (Uniformity was defined as U5-95% = D5%-D95%/Dmean. U5-95% for PTV_WAR was 0.34 ± 0.05 and 0.32 ± 0.06 (IMRT6 and IMRT15, 0.30 ± 0.03 and 0.26 ± 0.04 (RA6 and RA15; for PTV_Pelvis, it resulted equal to 0.1 for all techniques. For organs at risk, small differences were observed between the techniques. MU resulted 3130 ± 221 (IMRT6, 2841 ± 318 (IMRT15, 538 ± 29 (RA6, 635 ± 139 (RA15; the average measured treatment time was 18.0 ± 0.8 and 17.4 ± 2.2 minutes (IMRT6 and IMRT15 and 4.8 ± 0.2 (RA6 and RA15. GAIIMRT6 = 97.3 ± 2.6%, GAIIMRT15 = 94.4 ± 2.1%, GAIRA6 = 98.7 ± 1.0% and GAIRA15 = 95.7 ± 3.7%. Conclusion RapidArc showed to be a solution to WAR treatments offering good dosimetric features with significant logistic improvements compared to IMRT.

  15. Combining oncolytic virotherapy with p53 tumor suppressor gene therapy

    OpenAIRE

    Bressy, Christian; Hastie, Eric; Grdzelishvili, Valery Z.

    2017-01-01

    Oncolytic virus (OV) therapy utilizes replication-competent viruses to kill cancer cells, leaving non-malignant cells unharmed. With the first U.S. Food and Drug Administration-approved OV, dozens of clinical trials ongoing, and an abundance of translational research in the field, OV therapy is poised to be one of the leading treatments for cancer. A number of recombinant OVs expressing a transgene for p53 (TP53) or another p53 family member (TP63 or TP73) were engineered with the goal of gen...

  16. Animal models testing monotherapy versus combination antifungal therapy: lessons learned and future directions.

    Science.gov (United States)

    Clemons, Karl V; Stevens, David A

    2006-08-01

    The continued rise in serious fungal infections and rises in therapy failure dictate that more efficacious therapies be developed. Combination therapy using available drugs is an attractive choice, yet primarily only anecdotal clinical data are available. We review here data from animal models as an indicator of future potential. The primary data are from murine studies and we will briefly review chemotherapeutic combination studies, some showing benefit over monotherapy and some showing no benefit over monotherapy. In addition, we will address the potential of immunotherapy in combination with conventional therapy. The data derived from animal model studies of antifungal drug efficacy have proven to be predictive of clinical utility. Studies on combination therapy will prove useful to the clinician in evaluating courses of treatment, especially where clinical-trial data are not available or probable in the future.

  17. Combination Therapy in Asthma: A Review | Saleh | Nigerian ...

    African Journals Online (AJOL)

    Background: Asthma can be defined as a chronic inflammatory disease of the airways that is reversible either spontaneously or by treatment. Despite the exponential increase in asthma research, the prevalence of asthma is on the increase, especially in children and young adults in the western societies. Inhaled therapies

  18. Development of Combination Therapy with Anti-Cancer Drugs

    NARCIS (Netherlands)

    Leijen, S.

    2013-01-01

    This thesis describes early clinical trials with anti-cancer drugs in combination with commonly applied and registered chemotherapy and single agent studies with compounds that are intended for use in combination with registered or other targeted anti-cancer drugs. Gemcitabine is a prodrug that

  19. Impact of adequate empirical combination therapy on mortality from bacteremic Pseudomonas aeruginosa pneumonia

    Directory of Open Access Journals (Sweden)

    Park So-Youn

    2012-11-01

    Full Text Available Abstract Background Pseudomonas aeruginosa has gained an increasing amount of attention in the treatment of patients with pneumonia. However, the benefit of empirical combination therapy for pneumonia remains unclear. We evaluated the effects of adequate empirical combination therapy and multidrug-resistance in bacteremic Pseudomonas pneumonia on the mortality. Methods A retrospective cohort study was performed at the 2,700-bed tertiary care university hospital. We reviewed the medical records of patients with bacteremic pneumonia between January 1997 and February 2011. Patients who received either inappropriate or appropriate empirical therapy were compared by using marginal structural model. Furthermore, we investigated the direct impact of combination therapy on clinical outcomes in patients with monomicrobial bacteremic pneumonia. Results Among 100 consecutive patients with bacteremic Pseudomonas pneumonia, 65 patients were classified in the adequate empirical therapy group, 32 of whom received monotherapy and 33 combination therapy. In the marginal structural model, only inadequate therapy was significantly associated with 28-day mortality (p = 0.02, and multidrug-resistance was not a significant risk factor. To examine further the direct impact of combination therapy, we performed a subgroup analysis of the 65 patients who received adequate therapy. Multivariate logistic regression analysis identified absence of septic shock at the time of bacteremia (OR, 0.07; 95% CI, 0.01-0.49; p = 0.008, and adequate combination therapy (OR, 0.05; 95% CI, 0.01-0.34; p = 0.002 as variables independently associated with decreased all-cause 28-day mortality. Conclusions Our study suggests that adequate empirical combination therapy can decrease mortality in patients with bacteremic Pseudomonas pneumonia.

  20. Cancer prevention and treatment using combination therapy with plant- and animal-derived compounds.

    Science.gov (United States)

    Uzoigwe, Jacinta; Sauter, Edward R

    2012-11-01

    Compounds naturally occurring in plants and animals play an essential role in the prevention and treatment of various cancers. There are more than 100 plant- and animal-based natural compounds currently in clinical use. Similar to synthetic compounds, these natural compounds are associated with dose-related toxicity that limits efficacy. Scientists have investigated combination therapy with compounds that have different toxicities in order to optimize efficacy. These combination therapies may work additively or synergistically, there may be no effect or they may promote tumor formation. Combination therapy with agents that have similar mechanisms of action may increase toxicity. In this article, combination therapies that have been investigated, their rationale, mechanism of action and findings are reviewed. When the data warrant it, combined (pharmacologic and natural; two or more natural) interventions that appear to increase efficacy (compared with monotherapy) while minimizing toxicity have been highlighted.

  1. Hyperbaric oxygen therapy combined with Schwann cell transplantation promotes spinal cord injury recovery

    Directory of Open Access Journals (Sweden)

    Chuan-gang Peng

    2015-01-01

    Full Text Available Schwann cell transplantation and hyperbaric oxygen therapy each promote recovery from spinal cord injury, but it remains unclear whether their combination improves therapeutic results more than monotherapy. To investigate this, we used Schwann cell transplantation via the tail vein, hyperbaric oxygen therapy, or their combination, in rat models of spinal cord contusion injury. The combined treatment was more effective in improving hindlimb motor function than either treatment alone; injured spinal tissue showed a greater number of neurite-like structures in the injured spinal tissue, somatosensory and motor evoked potential latencies were notably shorter, and their amplitudes greater, after combination therapy than after monotherapy. These findings indicate that Schwann cell transplantation combined with hyperbaric oxygen therapy is more effective than either treatment alone in promoting the recovery of spinal cord in rats after injury.

  2. Efficacy and safety of a ceramide containing moisturizer followed by fixed-dose clindamycin phosphate 1.2%/benzoyl peroxide 2.5% gel in the morning in combination with a ceramide containing moisturizer followed by tretinoin 0.05% gel in the evening for the treatment of facial acne vulgaris.

    Science.gov (United States)

    Zeichner, Joshua A; Patel, Rita V; Haddican, Madelaine; Wong, Vicky

    2012-06-01

    Combination therapy addressing multiple pathogenic factors should be used to achieve optimal outcomes in treating acne. The following study demonstrated both safety and efficacy of fixed-dose clindamycin phosphate 1.2%/benzoyl peroxide 2.5% in the morning with micronized tretinoin 0.05% gel in the evening. Both products were applied to the skin following the use of a ceramide containing moisturizing lotion.

  3. [Effect of combined application of ozone therapy and gravitational therapy on the remote results of complex treatment of geriatric patients].

    Science.gov (United States)

    Makarov, I V; Shchukin, Yu V; Lukashova, A V

    2017-01-01

    The article presents the remote results of treatment of an obliterating atherosclerosis of arteries of the lower extremities of the II stage at patients of advanced and senile age after the combined use of ozone therapy and gravitational therapy. We performed a prospective randomized study in three parallel groups (139 patients). The 1st group (n=57) received standard medical therapy in combination with ozone therapy; the group was divided into two subgroups: for patients of subgroup 1a (n=28) - intravenous ozonized physiological solution was performed, for patients of subgroup 1b (n=29) - major ozonized autohemotherapy. For patients of the 2nd group (n=62) - a comprehensive treatment, including gravitational therapy in addition to medical ozone, was carried out. In this group were also identified two subgroups: subgroup 2a (n=31) - patients received standard medical therapy in combination with ozonized physiological solution and gravitational therapy, subgroup 2b (n=31) - standard medical therapy in conjunction with major ozonized autohemotherapy and gravitational therapy. The 3rd control group (n=20) included patients, who received only standard medical therapy. Dynamics of changes of a stage of a disease and the number of surgeries in the remote period was estimated (up to 7 years). After 6 months of follow-on stages of the distribution of the disease patients significantly (p>0,05) did not differ from the initial amount. Analysis of survival and probable risk at 7 years of follow-Cox regression method revealed a maximum efficiency in the subgroup 2a where the risk of probability of surgeries and also increases in a stage of a disease effectively decreased.

  4. Optimization of biological phosphorus and ammonia removal in a combined fixed and suspended growth wastewater treatment system: Final report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1994-12-31

    This project was conducted to optimize design and operational criteria for enhanced biological phosphorus removal and nitrification of ammonia in the fixed growth reactor-suspended growth reactor (FGR-SGR) process. The research completed the investigation of optimum hydraulic retention times for biological phosphorus removal in both the unaerated and aerated phases of the suspended growth components of the FGR-SGR system, including an assessment of the possibility of reducing suspended growth aeration requirements by using oxidized forms of nitrogen rather than dissolved oxygen for biological phosphorus uptake; investigated the effects on biological phosphorus removal and nitrification of varying the internal recycle flow rates; and investigated the optimum solids retention time, or the optimum operating mixed liquor suspended solids concentration, in the suspended growth component of the system for biological phosphorus removal and nitrification-denitrification.

  5. The use of combination therapy in pulmonary arterial hypertension: new developments

    Directory of Open Access Journals (Sweden)

    N. Galiè

    2009-09-01

    Full Text Available There is a strong clinical rationale for combination therapy in pulmonary arterial hypertension (PAH, as several pathological pathways have been implicated in its pathogenesis and no single agent has yet been shown to deliver completely satisfactory results. Registry data indicate that use of combination therapy is in fact common in existing clinical practice, even though support has been largely empirical or derived from small-scale observational studies. Data from large, adequately powered, randomised controlled trials of combination therapy in PAH are now emerging and suggest that combination therapy may be clinically beneficial. Studies of bosentan in combination with prostanoids and phosphodiesterase (PDE-5 inhibitors show consistent evidence of improvements in exercise capacity compared with placebo. Similar improvements have been observed with PDE-5 inhibitors in combination with prostanoids. The appropriate timing of combination therapy requires further evaluation but goal-oriented therapy using combinations of oral and inhaled drugs has been shown to provide acceptable long-term results in patients with advanced PAH. Monitoring should be performed regularly and be based on repeatable, noninvasive, measurable parameters that have prognostic value.

  6. Possible artemisinin-based combination therapy-resistant malaria in Nigeria: a report of three cases

    Directory of Open Access Journals (Sweden)

    Nnennaya Anthony Ajayi

    2013-07-01

    Full Text Available Artemisinin-based combination therapy-resistant malaria is rare in Sub-Saharan Africa. The World Health Organization identifies monitoring and surveillance using day-3 parasitaemia post-treatment as the standard test for identifying suspected artemisinin resistance. We report three cases of early treatment failure due to possible artemisinin-based combination therapy-resistant Plasmodium falciparum malaria. All cases showed adequate clinical and parasitological responses to quinine. This study reveals a need to re-evaluate the quality and efficacy of artemisinin-based combination therapy agents in Nigeria and Sub-Saharan Africa.

  7. How to evaluate combination therapy using interferon and nucleos(tide analogues

    Directory of Open Access Journals (Sweden)

    CHEN Lu

    2016-11-01

    Full Text Available Chronic hepatitis B is still one of the most important chronic diseases in China because of its high relevance to liver cirrhosis and hepatic cell cancer (HCC. Currently, interferon and nucleos(tide analogues are two main treatments for chronic hepatitis B, but they have advantages and disadvantages. More investigations are needed to explore better ways for treating this disease, and combination therapy might be one of the options. This article analyzes the advances in various combination therapies and points out views about the selection of combination therapies and patients.

  8. Overcoming tumor resistance by heterologous adeno-poxvirus combination therapy

    Directory of Open Access Journals (Sweden)

    Markus Vähä-Koskela

    2014-01-01

    Full Text Available Successful cancer control relies on overcoming resistance to cell death and on activation of host antitumor immunity. Oncolytic viruses are particularly attractive in this regard, as they lyse infected tumor cells and trigger robust immune responses during the infection. However, repeated injections of the same virus promote antiviral rather than antitumor immunity and tumors may mount innate antiviral defenses to restrict oncolytic virus replication. In this article, we have explored if alternating the therapy virus could circumvent these problems. We demonstrate in two virus-resistant animal models a substantial delay in antiviral immune- and innate cellular response induction by alternating injections of two immunologically distinct oncolytic viruses, adenovirus, and vaccinia virus. Our results are in support of clinical development of heterologous adeno-/vaccinia virus therapy of cancer.

  9. Combination antiretroviral therapy and the risk of myocardial infarction

    NARCIS (Netherlands)

    Friis-Moller, N; Sabin, CA; Weber, R; Monforte, AD; El-Sadr, WM; Reiss, P; Thiebaut, R; Morfeldt, L; De Wit, S; Pradier, C; Calvo, G; Law, MG; Kirk, O; Phillips, AN; Lundgren, JD; Lundgren, JD; Weber, R; Monteforte, AD; Bartsch, G; Reiss, P; Dabis, F; Morfeldt, L; De Wit, S; Pradier, C; Calvo, G; Law, MG; Kirk, O; Phillips, AN; Houyez, F; Loeliger, E; Tressler, R; Weller, I.; Friis-Moller, N; Sabin, CA; Sjol, A; Lundgren, JD; Sawitz, A; Rickenbach, M; Pezzotti, P; Krum, E; Meester, R; Lavignolle, V.; Sundstrom, A; Poll, B; Fontas, E; Torres, F; Petoumenos, K; Kjaer, J; Hammer, S; Neaton, J; Sjol, A; de Wolf, F; van der Ven, E; Zaheri, S; Van Valkengoed, L; Meester, R; Bronsveld, W; Weigel, H; Brinkman, K; Frissen, P; ten Veen, J; Hillbrand, M; Schieveld, S; Mulder, J; van Gorp, E; Meenhorst, P; Danner, S; Claessen, F; Perenboom, R; Schattenkerk, JKE; Godfried, M; Lange, J; Lowe, S; van der Meer, J; Nellen, F; Pogany, K; van der Poll, T; Reiss, R; Ruys, T; Wit, F; Richter, C; van Leusen, R; Vriesendorp, R; Jeurissen, F; Kauffmann, R; Koger, E; Brevenboer, B; Sprenger, HG; Law, G; ten Kate, RW; Leemhuis, M; Schippers, E; Schrey, G; van der Geest, S; Verbon, A; Koopmans, P; Keuter, M; Telgt, D; van der Ven, A; van der Ende, Marchina E.; Gyssens, I.; de Marie, S; Juttmann, J; van der Heul, C; Schneider, M; Borleffs, J; Hoepelman, I.; Jaspers, C; Matute, A; Schurink, C; Blok, W; Salamon, R; Beylot, J; Dupon, M; Le Bras, M; Pellegrin, JL; Ragnaud, JM; Dabis, F; Chene, G; Jacqmin-Gadda, H; Rhiebaut, R; Lawson-Ayayi, S; Lavignolle, V.; Balestre, E; Blaizeau, MJ; Decoin, M; Formaggio, AM; Delveaux, S; Labarerre, S; Uwamaliya, B; Vimard, E; Merchadou, L; Palmer, G; Touchard, D; Dutoit, D; Pereira, F; Boulant, B; Beylot, J; Morlat, P; Bonarek, M; Bonnet, F; Coadou, B; Gelie, P; Jaubert, D; Nouts, C; Lacoste, D; Dupon, M; Dutronc, H; Cipriano, G; Lafarie, S; Chossat, I.; Lacut, JY; Leng, B; Pellegrin, JL; Mercie, P; Viallard, JF; Faure, I.; Rispal, P; Cipriano, C; Tchamgoue, S; Le Bras, M; Djossou, F; Malvy, D; Pivetaud, JP; Ragnaud, JM; Chambon, D; De La Taille, C; Galperine, T; Lafarie, S; Neau, D; Ochoa, A; Beylot, C; Doutre, MS; Bezian, JH; Moreau, JF; Taupin, JL; Conri, C; Constans, J; Couzigou, P; Castera, L; Fleury, H; Lafon, ME; Masquelier, B; Pellegrin, I.; Trimoulet, P; Moreau, F; Mestre, C; Series, C; Taytard, A; Law, M; Petoumenos, K; Bal, J; Mijch, A; Watson, K; Roth, N; Wood, H; Austin, D; Gowers, A; Baker, B; McFarlane, R; Carr, A; Cooper, D; Chuah, J; Fankhauser, W; Mallal, S; Skett, J; Calvo, G; Torres, F; Mateau, S; Domingo, P; Sambeat, MA; Gatell, J; Del Cacho, E; Cadafalch, J; Fuster, M; Codina, C; Sirera, G; Vaque, A; Clumeck, N; De Wit, S; Gerard, M; Hildebrand, M; Kabeya, K; Konopnicki, D; Payen, MC; Poll, B; Van Laethem, Y; Neaton, J; Bartsch, G; El-Sadr, WM; Krum, E; Thompson, G; Wentworth, D; Luskin-Hawk, R; Telzak, E; El-Sadr, WM; Abrams, DI; Cohn, D; Markowitz, N; Arduino, R; Mushatt, D; Friedland, G; Perez, G; Tedaldi, E; Fisher, E; Gordin, F; Crane, LR; Sampson, J; Baxter, J; Kirk, O; Mocroft, A; Phillips, AN; Lundgren, JD; Vetter, N; Clumeck, N; Hermans, P; Colebunders, R; Machala, L; Nielsen, J; Benfield, T; Gerstoft, J; Katzenstein, T; Roge, B; Skinhoj, P; Pedersen, C; Katlama, C; Viard, JP; Saint-Marc, T; Vanhems, P; Pradier, C; Dietrich, M; Manegold, C; van Lunzen, J; Miller, V.; Staszewski, S; Bieckel, M; Goebel, FD; Salzberger, B; Rockstroh, J; Kosmidis, J; Gargalianos, P; Sambatakou, H; Perdios, J; Panos, G; Karydis, I.; Filandras, A; Banhegyi, D; Mulcahy, F; Yust, I.; Turner, D; Pollack, S; Ben-Ishai, Z; Bentwich, Z; Maayan, S; Vella, S; Chiesi, A; Arici, C; Pristera, R; Mazzotta, F; Gabbuti, A; Esposito, R; Bedini, A; Chirianni, A; Montesarchio, E; Vullo, V.; Santopadre, P; Narciso, P; Antinori, A; Franci, P; Zaccarelli, M; Lazzarin, A; Finazzi, R; Monforte, VO; Hemmer, R; Staub, T; Reiss, P; Bruun, J; Maeland, A; Ormaasen, V.; Knysz, B; Gasiorowski, J; Horban, A; Prokopowicz, D; Boron-Kaczmarska, A; Pnyka, M; Beniowski, M; Trocha, H; Antunes, F; Mansinho, K; Proenca, R; Gonzalez-Lahoz, J; Diaz, B; Garcia-Benayas, T; Martin-Carbonero, L; Soriano, V.; Clotet, B; Jou, A; Conejero, J; Tural, C; Gatell, JM; Miro, JM; Blaxhult, A; Heidemann, B; Pehrson, P; Ledergerber, B; Weber, R; Francioli, P; Telenti, A; Hirschel, B; Soravia-Dunand, V.; Furrer, H; Fisher, M; Brettle, R; Barton, S; Johnson, AM; Mercey, D; Loveday, C; Johnson, MA; Pinching, A; Parkin, J; Weber, J; Scullard, G; Morfeldt, L; Thulin, G; Sunstrom, A; Akerlund, B; Koppel, K; Karlsson, A; Flamholc, L; Hakangard, C; Monforte, AD; Pezzotti, P; Moroni, M; Monforte, AD; Cargnel, A; Merli, S; Vigevani, GM; Pastecchia, C; Lazzarin, A; Novati, R; Caggese, L; Moioli, C; Mura, MS; Mannazzu, M; Suter, F; Arici, C; Manconi, PE; Piano, P; Mazzotta, F; Lo Caputo, S; Poggio, A; Bottari, G; Pagano, G; Alessandrini, A; Scasso, A; Vincenti, A; Abbadesse, V.; Mancuso, S; Alberici, F; Ruggieri, A; Arlotti, M; Ortolani, P; De Lalla, F; Tositti, G; Piersantelli, N; Piscopo, R; Raise, E; Pasquinucci, S; Soscia, F; Tacconi, L; Tirelli, U; Nasti, G; Santoro, D; Pusterla, L; Carosi, G; Castelli, F; Cadeo, G; Vangi, D; Carnevale, G; Galloni, D; Filice, G; Bruno, R; Sinicco, A; Sciandra, M; Caramello, P; Gennero, L; Soranzo, ML; Bonasso, M; Rizzardini, G; Migliorino, G; Chiodo, F; Colangeli, V.; Magnani, G; Ursitti, M; Menichetti, F; Martinelli, C; Esposito, R; Mussini, C; Ghinelli, F; Sighinolfi, L; Coronado, O; Zauli, T; Ballardini, G; Montroni, M; Zoli, A; Petrelli, E; Cioppi, A; Ortona, L; De Luca, A; Petrosillo, N; Noto, P; Narciso, P; Salcuni, P; Antinori, A; De Longis, P; Vullo, V.; Lichtner, M; Pastore, G; Minafra, G; Chiriann, A; Loiacono, L; Piazza, M; Nappa, S; Abrescia, N; De Marco, M; Colomba, A; Prestileo, T; De Stefano, C; La Gala, A; Ferraro, T; Scerbo, A; Grima, P; Tundo, P; Pizzigallo, E; D'Alessandro, M; Grisorio, B; Ferrara, S; Pradier, C; Fontas, E; Caissotti, C; Dellamonica, P; Bentz, L; Bernard, E; Chaillou, S; De Salvador-Guillouet, F; Durant, J; Guttman, R; Heripret, L; Mondain-Miton, V.; Perbost, I.; Prouvost-Keller, B; Pugliese, P; Rahelinirina, V.; Roger, PM; Vandenbos, F; Bernasconi, E; Bucher, H; Burgisser, P; Cattacin, S; Egger, M; Erb, P; Fierz, W; Fischer, M; Flepp, M; Fontana, A; Francioli, P; Furrer, HJ; Gorgievski, M; Hirschel, B; Kaiser, L; Kind, C; Klimkait, T; Ledergerber, B; Lauper, U; Opravil, M; Paccaud, F; Pantaleo, G; Perrin, L; Piffaretti, JC; Rickenbach, M; Rudin, C; Schupbach, J; Speck, R; Telenti, A; Trkola, A; Vernazza, P; Weber, R; Yerly, S; Ten Napel, C.

    2003-01-01

    Background: It remains controversial whether exposure to combination antiretroviral treatment increases the risk of myocardial infarction. Methods: In this prospective observational study, we enrolled 23,468 patients from 11 previously established cohorts from December 1999 to April 2001 and

  10. Combinations of Radiation Therapy and Immunotherapy for Melanoma: A Review of Clinical Outcomes

    Energy Technology Data Exchange (ETDEWEB)

    Barker, Christopher A., E-mail: barkerc@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Postow, Michael A. [Department of Medicine, Melanoma and Sarcoma Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2014-04-01

    Radiation therapy has long played a role in the management of melanoma. Recent advances have also demonstrated the efficacy of immunotherapy in the treatment of melanoma. Preclinical data suggest a biologic interaction between radiation therapy and immunotherapy. Several clinical studies corroborate these findings. This review will summarize the outcomes of studies reporting on patients with melanoma treated with a combination of radiation therapy and immunotherapy. Vaccine therapies often use irradiated melanoma cells, and may be enhanced by radiation therapy. The cytokines interferon-α and interleukin-2 have been combined with radiation therapy in several small studies, with some evidence suggesting increased toxicity and/or efficacy. Ipilimumab, a monoclonal antibody which blocks cytotoxic T-lymphocyte antigen-4, has been combined with radiation therapy in several notable case studies and series. Finally, pilot studies of adoptive cell transfer have suggested that radiation therapy may improve the efficacy of treatment. The review will demonstrate that the combination of radiation therapy and immunotherapy has been reported in several notable case studies, series and clinical trials. These clinical results suggest interaction and the need for further study.

  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.

    Directory of Open Access Journals (Sweden)

    Daniel G Wootton

    2008-03-01

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

  12. 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

    Science.gov (United States)

    Wootton, Daniel G.; Opara, Hyginus; Biagini, Giancarlo A.; Kanjala, Maxwell K.; Duparc, Stephan; Kirby, Paula L.; Woessner, Mary; Neate, Colin; Nyirenda, Maggie; Blencowe, Hannah; Dube-Mbeye, Queen; Kanyok, Thomas; Ward, Stephen; Molyneux, Malcolm; Dunyo, Sam; Winstanley, Peter A.

    2008-01-01

    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

  13. Pharmacokinetic Characteristics and Clinical Efficacy of an SGLT2 Inhibitor Plus DPP-4 Inhibitor Combination Therapy in Type 2 Diabetes.

    Science.gov (United States)

    Scheen, André J

    2017-07-01

    Type 2 diabetes (T2D) generally requires a combination of several pharmacological approaches to control hyperglycaemia. Combining a sodium-glucose cotransporter type 2 inhibitor (SGLT2I, also known as gliflozin) and a dipeptidyl peptidase-4 inhibitor (DPP-4I, also known as gliptin) appears to be an attractive strategy because of complementary modes of action. This narrative review analyzes the pharmacokinetics and clinical efficacy of different combined therapies with an SGLT2I (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, ipragliflozin, luseogliflozin, tofogliflozin) and DPP-4I (linagliptin, saxagliptin, sitagliptin, teneligliptin). Drug-drug pharmacokinetic interaction studies do not show any significant changes in peak concentrations (C max) and total exposure (area under the curve of plasma concentrations [AUC]) of either drug when they were administered together orally compared with corresponding values when each of them was absorbed alone. Two fixed-dose combinations (FDCs) are already available (dapagliflozin-saxagliptin, empagliflozin-linagliptin) and others are in development (ertugliflozin-sitagliptin). Preliminary results show bioequivalence of the two medications administered as FDC tablets when compared with coadministration of the individual tablets. Dual therapy is more potent than either monotherapy in patients treated with diet and exercise or already treated with metformin. SGLT2I and DPP-4I could be used as initial combination or in a stepwise approach. The additional glucose-lowering effect appears to be more marked when a gliflozin is added to a gliptin than when a gliptin is added to a gliflozin. Combining the two pharmacological options is safe and does not induce hypoglycaemia.

  14. Fixed herbal drug combination with and without butterbur (Ze 185) for the treatment of patients with somatoform disorders: randomized, placebo-controlled pharmaco-clinical trial.

    Science.gov (United States)

    Melzer, Jörg; Schrader, Ewald; Brattström, Axel; Schellenberg, Rüdiger; Saller, Reinhard

    2009-09-01

    Herbal drugs are often used in patients with somatoform disorders yet, the available evidence is limited. The aim of the present short-term study was to evaluate in a pharmaco-clinical trial the additional benefit of butterbur in a fixed herbal drug combination (Ze 185 = 4-combination versus 3-combination without butterbur and placebo) in patients with somatoform disorders.For a 2-week treatment in patients with somatization disorder (F45.0) and undifferentiated somatoform disorder (F45.1), 182 patients were randomized for a 3-arm trial (butterbur root, valerian root, passionflower herb, lemon balm leaf versus valerian root, passionflower herb, lemon balm leaf versus placebo). Anxiety (visual analogue scale - VAS) and depression (Beck's Depression Inventory - BDI) served as primary parameters, Clinical Global Impression (CGI) was a secondary parameter.The 4-combination was significantly superior to the 3-combination and placebo (4-combination > 3-combination > placebo) in all the primary and secondary parameters (PP-population). Analysis of the ITT population confirmed these results. As to safety, no serious adverse events occurred. In total 9 non-serious adverse events were documented but the distribution did not differ significantly between the treatment groups.This herbal preparation (Ze185) showed to be an efficacious and safe short-term treatment in patients with somatoform disorders.

  15. Influence of Fixed Combination of Metformin SR and Glimepiride on Carbohydrate, Lipid Metabolism and Arterial Wall Stiffness in Patients with Diabetes Mellitus Type 2

    Directory of Open Access Journals (Sweden)

    O.S. Larin

    2015-06-01

    Conclusions. Combined hypoglycemic therapy with glimepiride and metformin SR for 12 weeks resulted in a statistically significant improvement of carbohydrate and lipid metabolism, had no effect on anthropometric parameters and the total amount of adipose tissue, prevented the progression of arteriosclerosis of large vessels according to the indicators of arterial wall stiffness.

  16. Success of rechallenging dabrafenib and trametinib combination therapy after trametinib-induced rhabdomyolysis: a case report.

    Science.gov (United States)

    Muto, Yusuke; Ng, William; Namikawa, Kenjiro; Takahashi, Akira; Tsutsumida, Arata; Nishida, Makiko; Yamazaki, Naoya

    2018-01-29

    The mitogen-activated protein kinase pathway regulates cell growth and differentiation and is activated by BRAF mutations. BRAF mutations are present in about 40-50% of cutaneous melanomas. More than 90% of BRAF mutations are the V600E type. BRAF inhibitor (dabrafenib or vemurafenib) and MEK inhibitor (trametinib or cobimetinib) combination therapies are effective for BRAF-mutant advanced melanomas. A variety of side effects have been observed with combination therapy including pyrexia, fatigue, nausea, and vomiting. Rhabdomyolysis is one of the most severe adverse events, but it is very rare. Only two cases of rhabdomyolysis have been reported in clinical trials. A 41-year-old Japanese woman with cutaneous melanoma was started on a combination of dabrafenib and trametinib therapy after failure of immune checkpoint therapy. One month later, she complained of myalgia and fatigue and was shifted to our hospital. She was diagnosed with trametinib-induced rhabdomyolysis and showed improvement only with a high volume of fluid infusion. We stopped combination therapy, but there were no useful treatment options for her. After resuming dabrafenib, followed by trametinib, she did not have any problems. This is the first case of a patient with metastatic cutaneous melanoma who could recommence combination therapy after trametinib-associated rhabdomyolysis. We assume that not all patients experience recurrence of rhabdomyolysis in trametinib-induced rhabdomyolysis. As few cases have been reported, more information is needed. We have to evaluate safety carefully if rechallenging combination therapy.

  17. Impact of combined secondary prevention therapy after myocardial infarction: data from a nationwide French registry.

    Science.gov (United States)

    Danchin, Nicolas; Cambou, Jean-Pierre; Hanania, Guy; Kadri, Zena; Genès, Nathalie; Lablanche, Jean-Marc; Blanchard, Didier; Vaur, Laurent; Clerson, Pierre; Guéret, Pascal

    2005-12-01

    Several classes of medications improve survival in patients with coronary artery disease. Whether these medications, as used in the real world, have additive efficacy remains speculative. To assess whether patients discharged on combined secondary prevention medications after acute myocardial infarction (AMI) have improved 1-year survival, compared with the action of any single class of medications. Nationwide registry of consecutive patients admitted to intensive care units for AMI in November 2000 in France. Multivariate Cox regression analysis, including a propensity score for the prescription of combined therapy, was used. Of the 2119 patients discharged alive, 1095 (52%) were prescribed a combination of antiplatelet agents, beta-blockers, and statins (triple therapy), of whom 567 (27%) also received angiotensin-converting enzyme inhibitors (quadruple therapy) and 528 (25%) did not. One-year survival was 97% in patients receiving triple combination therapy versus 88% in those who received either none, 1, or 2 of these medications (P After multivariate adjustment including the propensity score, the hazard ratio for 1-year mortality in patients with triple combination therapy was 0.52 (95% CI 0.33-0.81). In patients with ejection fraction therapy had no additional prognostic value. Compared with the prescription of any single class of secondary prevention medications, combination therapy offers additional protection in patients with AMI.

  18. Explorations of combinational therapy in cancer : targeting the tumor and its microenvironment by combining chemotherapy with chemopreventive approaches

    NARCIS (Netherlands)

    Wijngaarden, Johannes Willem van

    2011-01-01

    One of the most effective anticancer therapy still remains chemotherapy, however, both used as single agent as in combinational regimens, chemotherapy still encounters the problem of therapeutic resistance. Limitations of chemotherapy have led to the exploration of alternative anti-cancer approaches

  19. Successful therapy of progressive rhino-orbital mucormycosis caused by Rhizopus arrhizus with combined and sequential antifungal therapy, surgery and hyperbaric therapy.

    Science.gov (United States)

    Imbernón, Adrián; Agud, José Luis; Cuétara, María Soledad; Casqueiro, José Carlos; Nuñez, Pilar; Domínguez, Alegría R; Bullido, Eusebio; Stchigel, Alberto M

    2014-10-01

    We present a case of rhino-orbitary mucormycosis which progressed despite liposomal amphotericin and early surgical debridement. Combined echinocandin and high dose liposomal amphotericin, repeated debridement, prolonged therapy with hyperbaric oxygen and continued therapy with posaconazole, along with strict diabetic control, allowed cure without disfigurement.

  20. Successful therapy of progressive rhino-orbital mucormycosis caused by Rhizopus arrhizus with combined and sequential antifungal therapy, surgery and hyperbaric therapy

    OpenAIRE

    Imbernón, Adrián; Agud, José Luis; Cuétara, María Soledad; Casqueiro, José Carlos; Nuñez, Pilar; Domínguez, Alegría R.; Bullido, Eusebio; Stchigel, Alberto M.

    2014-01-01

    10.1016/j.mmcr.2014.09.004 We present a case of rhino-orbitary mucormycosis which progressed despite liposomal amphotericin and early surgical debridement. Combined echinocandin and high dose liposomal amphotericin, repeated debridement, prolonged therapy with hyperbaric oxygen and continued therapy with posaconazole, along with strict diabetic control, allowed cure without disfigurement.

  1. Successful therapy of progressive rhino-orbital mucormycosis caused by Rhizopus arrhizus with combined and sequential antifungal therapy, surgery and hyperbaric therapy

    Directory of Open Access Journals (Sweden)

    Adrián Imbernón

    2014-10-01

    Full Text Available We present a case of rhino-orbitary mucormycosis which progressed despite liposomal amphotericin and early surgical debridement. Combined echinocandin and high dose liposomal amphotericin, repeated debridement, prolonged therapy with hyperbaric oxygen and continued therapy with posaconazole, along with strict diabetic control, allowed cure without disfigurement.

  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. Use of combination therapy with immunomodulators and immunosuppressants in treating multiple sclerosis.

    Science.gov (United States)

    Jeffery, Douglas R

    2004-12-28

    Immunomodulating agents have beneficial effects in the treatment of multiple sclerosis (MS), decreasing the frequency of relapses, the progression of disability, and MRI measures of disease activity. Despite the efficacy of these agents, many patients continue to show progression of disability, breakthrough relapses, and active disease on MRI. Therefore, clinicians have employed a variety of combinations of agents in an attempt to decrease disease activity in those with active disease despite standard immunomodulatory therapy. Although a variety of combination therapies have been used in clinical practice, there is a paucity of data available to guide clinical decision-making. A major pitfall in using combination therapy in the absence of data demonstrating safety is the possibility that the agent added to the primary therapy may have no effect or, worse, may antagonize the effect of the primary agent. The combination of mitoxantrone and interferon beta (IFNbeta) appears safe in short-term studies from a toxicity standpoint and is associated with a reduction in relapse rates, a decrease in the frequency of enhancing lesions, and a decrease in T2 lesion burden. Other combinations that appear safe in preliminary studies include IFNbeta-1a and methotrexate, IFNbeta-1a and azathioprine, and mitoxantrone plus methylprednisolone. The decision to use combination therapy in patients with a suboptimal response to monotherapy should be considered early and not be delayed until disability becomes advanced. This review discusses the available data regarding the combination of standard immunomodulatory therapy with immunosuppressive agents.

  4. Combination therapy with leflunomide and genetic engineering biological agents

    Directory of Open Access Journals (Sweden)

    Nataliya Vladimirovna Chichasova

    2011-01-01

    Full Text Available The paper gives data on the use of a combination of genetic engineering biological agents (GEBAs and leflunomide in patients with rheumatoid arthritis (RA. In accordance with the international guidelines, the majority of GEBAs should be given in a combination with methotrexate (MTX, which increases the efficacy of a number of GEBAs (tumor necrosis factor-α inhibitors, rituximab and affects tolerability (remikeid, humira. However, MTX cannot be always used in real practice. The data given in the paper on the efficiency and safety of the coadministration of leflunomide and a GEBA in patients with active RA, which are based on the results of randomized studies and national registers, including the Russian one, point to the compatibility of the results of treatment with this and GEBA-MTX combinations.

  5. Combination therapy with leflunomide and genetic engineering biological agents

    Directory of Open Access Journals (Sweden)

    Nataliya Vladimirovna Chichasova

    2011-06-01

    Full Text Available The paper gives data on the use of a combination of genetic engineering biological agents (GEBAs and leflunomide in patients with rheumatoid arthritis (RA. In accordance with the international guidelines, the majority of GEBAs should be given in a combination with methotrexate (MTX, which increases the efficacy of a number of GEBAs (tumor necrosis factor-α inhibitors, rituximab and affects tolerability (remikeid, humira. However, MTX cannot be always used in real practice. The data given in the paper on the efficiency and safety of the coadministration of leflunomide and a GEBA in patients with active RA, which are based on the results of randomized studies and national registers, including the Russian one, point to the compatibility of the results of treatment with this and GEBA-MTX combinations.

  6. Combination of negative pressure wound therapy and acoustic pressure wound therapy for treatment of infected surgical wounds: a case series.

    Science.gov (United States)

    Liguori, Paul A; Peters, Kim L; Bowers, Jolene M

    2008-05-01

    The optimal wound therapy for healing infected wounds post surgery or surgical debridement has not been established. Negative pressure wound therapy and acoustic pressure wound therapy are advanced wound-healing modalities that apply forms of mechanical pressure to wound tissue in an effort to promote healing by stimulating cellular proliferation. Using a combination of negative pressure wound therapy and acoustic pressure wound therapy was evaluated in a series of six patients with large, infected surgical wounds presenting with moderate to large amounts of serosanguineous drainage. After concurrent treatment with both modalities (range: 4 to 12 weeks), wound volume was reduced by 99% to 100% in all wounds except one wound for which depth at end of treatment was not measurable due to hypergranulation. Similarly, wound surface area was reduced by 82% to 100%, with the exception of the hypergranular wound, which decreased in size by 60%. Serosanguineous wound drainage was reduced in four wounds and remained unchanged in two wounds.

  7. Efficacy of Pharmacotherapy and Cognitive Therapy, Alone and in Combination in Major Depressive Disorder

    OpenAIRE

    Rahimi, A; F. Shamsaie; M.K. Zarabian; Sedehi, M.

    2008-01-01

    Introduction & Objective: Patients with Major depressive are difficult to treat, and the relative efficacy of medications and cognitive therapy in the treatment of depression is still a matter of deabath. The purpose of this study was to compare the efficacies of antidepressant medication, cognitive therapy and combination of cognitive therapy and antidepressant medication. Materials & Methods: In an experimental study, 120 depressive patients were randomly selected and divided in three grou...

  8. Effect of Decompression Therapy Combined with Joint Mobilization on Patients with Lumbar Herniated Nucleus Pulposus

    National Research Council Canada - National Science Library

    Lee, Younghwa; Lee, Chang-Ryeol; Cho, Misuk

    2012-01-01

    [Purpose] The purpose of this study was to examine the effects of decompression therapy combined with joint mobilization on the pain and range of motion of patients with lumbar herniated nucleus pulposus. [Subjects...

  9. Effectiveness of a positive psychology intervention combined with cognitive behavioral therapy in university students

    National Research Council Canada - National Science Library

    Rosario Josefa Marrero; Mónica Carballeira; Sabrina Martín; Miriam Mejías

    2016-01-01

      The aim of this study was to design and implement a positive intervention combined with cognitive-behavioral therapy to enhance subjective and psychological well-being and other positive functioning...

  10. Gametocyte carriage in uncomplicated Plasmodium falciparum malaria following treatment with artemisinin combination therapy

    DEFF Research Database (Denmark)

    Abdulla, Salim; Achan, Jane; Adam, Ishag

    2016-01-01

    Background: Gametocytes are responsible for transmission of malaria from human to mosquito. Artemisinin combination therapy (ACT) reduces post-treatment gametocyte carriage, dependent upon host, parasite and pharmacodynamic factors. The gametocytocidal properties of antimalarial drugs are importa...

  11. Adjuvant combined ozone therapy for extensive wound over tibia

    Directory of Open Access Journals (Sweden)

    Prasham Shah

    2011-01-01

    Full Text Available Disinfectant and antibacterial properties of ozone are utilized in the treatment of nonhealing or ischemic wounds. We present here a case of 59 years old woman with compartment syndrome following surgical treatment of stress fracture of proximal tibia with extensively infected wound and exposed tibia to about 4/5 of its extent. The knee joint was also infected with active pus draining from a medial wound. At presentation the patient had already taken treatment for 15 days in the form of repeated wound debridements and parenteral antibiotics, which failed to heal the wound and she was advised amputation. Topical ozone therapy twice daily and ozone autohemotherapy once daily were given to the patient along with daily dressings and parenteral antibiotics. Within 5 days, the wound was healthy enough for spilt thickness skin graft to provide biological dressing to the exposed tibia bone. Topical ozone therapy was continued for further 5 days till the knee wound healed. On the 15th day, implant removal, intramedullary nailing, and latissimus dorsi pedicle flap were performed. Both the bone and the soft tissue healed without further complications and at 20 months follow-up, the patient was walking independently with minimal disability.

  12. Adjuvant combined ozone therapy for extensive wound over tibia.

    Science.gov (United States)

    Shah, Prasham; Shyam, Ashok K; Shah, Sambhav

    2011-07-01

    Disinfectant and antibacterial properties of ozone are utilized in the treatment of nonhealing or ischemic wounds. We present here a case of 59 years old woman with compartment syndrome following surgical treatment of stress fracture of proximal tibia with extensively infected wound and exposed tibia to about 4/5 of its extent. The knee joint was also infected with active pus draining from a medial wound. At presentation the patient had already taken treatment for 15 days in the form of repeated wound debridements and parenteral antibiotics, which failed to heal the wound and she was advised amputation. Topical ozone therapy twice daily and ozone autohemotherapy once daily were given to the patient along with daily dressings and parenteral antibiotics. Within 5 days, the wound was healthy enough for spilt thickness skin graft to provide biological dressing to the exposed tibia bone. Topical ozone therapy was continued for further 5 days till the knee wound healed. On the 15(th) day, implant removal, intramedullary nailing, and latissimus dorsi pedicle flap were performed. Both the bone and the soft tissue healed without further complications and at 20 months follow-up, the patient was walking independently with minimal disability.

  13. Gene Therapy for RAG-deficient Severe Combined Immunodeficiency

    NARCIS (Netherlands)

    K. Pike (Karin)

    2007-01-01

    textabstractSevere combined immunodeficiency (SCID) is a rare class of primary, inherited, immunodeficiency causing infants to suffer from persistent diarrhea, opportunistic infections and a failure to thrive. RAG proteins play a crucial role in the initiation of V(D)J recombination of

  14. Immunological therapy in urological malignancy: novel combination strategies.

    Science.gov (United States)

    Finley, David S; Pouliot, Frederic; Chin, Arnold I; Shuch, Brian; Pantuck, Alan J; Belldegrun, Arie S; Dekernion, Jean B

    2011-02-01

    At present, immunotherapy in urological malignancy is experiencing a renaissance, particularly with the emergence of a host of innovative cancer vaccines. Herein, we will review promising immunotherapeutic approaches and evaluate the data supporting their inclusion in novel combination strategies. © 2010 The Japanese Urological Association.

  15. An eight-week, multicentric, randomized, interventional, open-label, phase 4, parallel comparison of the efficacy and tolerability of the fixed combination of timolol maleate 0.5%/brimonidine tartrate 0.2% versus fixed combination of timolol maleate 0.5%/dorzolamide 2% in patients with elevated intraocular pressure.

    Science.gov (United States)

    Hatanaka, Marcelo; Grigera, Daniel E; Barbosa, Wilma L; Jordao, Marcelo; Susanna, Remo

    2008-12-01

    To compare the efficacy and tolerability of the fixed combination of timolol maleate 0.5%/brimonidine tartrate 0.2% versus fixed combination of timolol maleate 0.5%/dorzolamide 2% in patients with elevated intraocular pressure (IOP) over 8 weeks. This 8-week, multicentric, interventional, randomized, open-label, parallel group study was conducted at 4 centers in Brazil and 1 center in Argentina. Patients with open-angle glaucoma or ocular hypertension were randomized to receive bilaterally fixed combination of brimonidine/timolol maleate 0.5% or fixed combination of dorzolamide 2%/timolol 0.5% twice daily at 8:00 AM and 8:00 PM. A modified diurnal tension curve (8:00 AM, 10:30 AM, 02:00 PM, and 4:00 PM) followed by the water drinking test (WDT), which estimates IOP peak of diurnal tension curve, were performed in the baseline and week-8 visits. Adverse events data were recorded at each visit. A total of 210 patients were randomized (brimonidine/timolol, n=111; dorzolamide/timolol, n=99). Mean baseline IOP was 23.43+/-3.22 mm Hg and 23.43+/-4.06 mm Hg in the patients treated with brimonidine/timolol and dorzolamide/timolol, respectively (P=0.993). Mean diurnal IOP reduction after 8 weeks were 7.02+/-3.06 mm Hg and 6.91+/-3.67 mm Hg, respectively (P=0.811). The adjusted difference between groups (analysis of covariance) at week 8 was not statistically significant (P=0.847). Mean baseline WDT peak was 27.79+/-4.29 mm Hg in the brimonidine/timolol group and 27.68+/-5.46 mm Hg in the dorzolamide/timolol group. After 8 weeks of treatment, mean WDT peaks were 20.94+/-3.76 mm Hg (P<0.001) and 20.98+/-4.19 (P<0.001), respectively. The adjusted difference between groups (analysis of covariance) was not statistically significant (P=0.469). No statistical difference in terms of adverse events was found between groups. Both fixed combinations were capable of significantly reducing the mean diurnal IOP, mean diurnal peak, and mean WDT peak after 8 weeks of treatment. Also, both

  16. Ocular tolerance in rabbits after intracameral administration of a fixed combination of tropicamide, phenylephrine, and lidocaine with and without rinsing.

    Science.gov (United States)

    Nuijts, Rudy M M A; Mencucci, Rita; Viaud-Quentric, Karen; Elena, Pierre-Paul; Olmière, Céline; Behndig, Anders

    2017-05-01

    To evaluate the safety and tolerability of a single intracameral administration of a combined mydriatic (tropicamide and phenylephrine) and anesthetic (lidocaine) formulation (Mydrane) with or without rinsing. Iris Pharma, La Gaude, France. Experimental study. Sixty pigmented rabbits received 100 μL or 200 μL of the combination product or a placebo (sodium chloride 0.9%) by intracameral injection. For the combination product, separate groups were included with and without rinsing after administration. From day 1 day to day 7, assessments included general clinical and ocular observations, pupil diameter measurements, corneal assessments, confocal microscopy, and electroretinography (ERG). Necropsy examinations were performed at study completion at day 8. Rapid mydriasis, stable 24 minutes after injection and returning to baseline levels by day 1, was induced in all groups that received the combination mydriatic and anesthetic drug. Rinsing had no effect. The combination product induced no adverse effects on the anterior or posterior segment of the eye (ie, no increased corneal thickness and endothelial cell loss, no abnormalities in ERG). Slitlamp examination showed slightly increased anterior chamber inflammation with rinsing in both the study group and placebo group. This observation was not confirmed by aqueous flare examination. No toxic effects of the products were found on histological evaluation. The combination mydriatic and anesthetic drug administered to pigmented rabbits as a single intracameral injection at volumes of 100 μL and 200 μL was well tolerated with no ocular adverse effects and no effect on the corneal endothelium. Copyright © 2017 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

  17. Facilitating the use of COBRA combination therapy in early rheumatoid arthritis: a pilot implementation study.

    NARCIS (Netherlands)

    Tuyl, L.H.D. van; Plass, A.M.C.; Lems, W.F.; Voskuyl, A.E.; Kerstens, P.J.S.M.; Dijkmans, B.A.C.; Boers, M.

    2009-01-01

    OBJECTIVE: COBRA combination therapy is well known and has uncontested efficacy in the treatment of rheumatoid arthritis (RA). However, it is infrequently applied in Dutch clinical practice. Based on qualitative research on opinions of physicians and patients towards COBRA therapy, our study

  18. Combined spa-exercise therapy is effective in patients with ankylosing spondylitis: a randomized controlled trial

    NARCIS (Netherlands)

    van Tubergen, A.; Landewé, R.; van der Heijde, D.; Hidding, A.; Wolter, N.; Asscher, M.; Falkenbach, A.; Genth, E.; Thè, H. G.; van der Linden, S.

    2001-01-01

    To determine the efficacy of combined spa-exercise therapy in addition to standard treatment with drugs and weekly group physical therapy in patients with ankylosing spondylitis (AS). A total of 120 Dutch outpatients with AS were randomly allocated into 3 groups of 40 patients each. Group 1 (mean

  19. A Novel Combination of Thermal Ablation and Heat-Inducible Gene therapy for Breast Cancer Treatment

    Science.gov (United States)

    2009-04-01

    intensity focused ultrasound ( HIFU ) has been developed as an emerging non-invasive strategy for cancer treatment by thermal ablation of tumor tissue. The...feasibility of synergistic combination of HIFU thermal ablation and HIFU -induced gene therapy is interpreted both in vitro and in vivo using cancer...distribution. This work opens up a new paradigm for synergistic combination of HIFU thermal ablation with heat-induced gene therapy to improve the overall

  20. Therapeutic Cancer Vaccines in Combination with Conventional Therapy

    DEFF Research Database (Denmark)

    Andersen, Mads Hald; Junker, N.; Ellebaek, E.

    2010-01-01

    of proteins coupled to intrinsic properties of cancer cells. For example, proteins associated with drug resistance can be targeted, and form ideal target structures for use in combination with chemotherapy for killing of surviving drug resistant cancer cells. Proteins associated with the malignant phenotype...... can be targeted to specifically target cancer cells, but proteins targeted by immunotherapy may also simultaneously target cancer cells as well as suppressive cells in the tumor stroma....

  1. How should we sequence and combine novel therapies in CLL?

    Science.gov (United States)

    Davids, Matthew S

    2017-12-08

    With the recent approval of several effective and well-tolerated novel agents (NAs), including ibrutinib, idelalisib, venetoclax, and obinutuzumab, patients with chronic lymphocytic leukemia (CLL) have more therapeutic options than ever before. The availability of these agents is both an important advance for patients but also a challenge for practicing hematologist/oncologists to learn how best to sequence NAs, both with respect to chemoimmunotherapy (CIT) and to other NAs. The sequencing of NAs in clinical practice should be guided both by an individual patient's prognostic markers, such as FISH and immunoglobulin heavy chain variable region (IGHV)-mutation status, as well as the patient's medical comorbidities and goals of care. For older, frailer patients with lower-risk CLL prognostic markers, NA monotherapy may remain a mainstay of CLL treatment for years to come. For younger, fitter patients and those with higher-risk CLL, such as del(17p) or unmutated IGHV, combination approaches may prove to be more valuable than NA monotherapy. Trials are currently evaluating the efficacy of several such combination approaches, including NA plus anti-CD20 monoclonal antibody, NA plus NA (with or without anti-CD20 monoclonal antibody), and NA plus CIT. Given the tremendous efficacy of the already approved NAs, as well as the promising data for next generation NAs, the development of well-tolerated, highly effective combination strategies with curative potential for patients with CLL has become a realistic goal. © 2016 by The American Society of Hematology. All rights reserved.

  2. Combination therapy patterns and predictors of ADHD in commercially insured and Medicaid populations.

    Science.gov (United States)

    Molife, Cliff; Bernauer, Mark J; Farr, Amanda M; Haynes, Virginia S; Kelsey, Doug

    2012-09-01

    Several stimulant and nonstimulant medications are used alone or in combination to treat attention-deficit/hyperactivity disorder (ADHD). Little is known about the current prevalence and predictors of combination therapy. This analysis describes ADHD medication use focusing on combination versus monotherapy. Health insurance claims from the Truven Health MarketScan® Commercial Database and Multi-State Medicaid Database were analyzed for patients with an ADHD diagnosis (International Classification of Diseases, Ninth Revision codes 314.0x). Patients included were aged ≥ 6 years as of January 2010, continuously enrolled from July 2009 through December 2010, and had a claim for an ADHD medication in 2010. Medication use was measured in treatment months during 2010. Baseline demographic and clinical predictors of combination therapy (> 1 ADHD medication class in the same month) involving atomoxetine, long-acting stimulants, and α2-adrenergic agonists were explored using logistic regression, with generalized estimating equations to account for within-patient correlation between months. Commercially insured patients with ADHD (N = 211 226) were primarily aged 6 to 17 years (58.4%) and male (61.5%). Attention-deficit/hyperactivity disorder with hyperactivity was present in 15.8% of these patients. Combination therapy was used in 10.3% of 1 125 119 treatment months. Short-acting stimulants and α2-adrenergic agonists had the highest combination use (45.3% and 54.0%, respectively). Patients with ADHD insured through Medicaid (N = 125 104) were primarily aged 6 to 17 years (94.4%) and male (69.5%). Hyperactivity was present in 39.7% of these patients. Combination therapy was used in 24.0% of 721 986 treatment months. Short-acting stimulants, α2-adrenergic agonists, and intermediate-acting stimulants had the highest combination use (70.0%, 63.8%, and 51.8%, respectively). In multivariate models for both data sources, female patients were less likely to use combination

  3. Review of oral fixed-dose combination netupitant and palonosetron (NEPA) for the treatment of chemotherapy-induced nausea and vomiting.

    Science.gov (United States)

    Lorusso, Vito; Karthaus, Meinolf; Aapro, Matti

    2015-01-01

    Current guidelines recommend the combination of a neurokinin-1 (NK1) receptor antagonist (RA) and a 5-hydroxytryptamine-3 (5-HT3) RA, together with corticosteroids, in order to prevent chemotherapy-induced nausea and vomiting with anthracycline-cyclophosphamide and highly emetogenic chemotherapy, and it is to be considered with moderately emetogenic chemotherapy. Netupitant and palonosetron (NEPA) is a fixed-dose combination of netupitant, a novel, highly selective NK1 RA, and palonosetron, a new-generation 5-HT3 RA, targeting two major emetic pathways in a single oral capsule. In clinical trials, NEPA administered on day 1 together with dexamethasone was highly effective and well tolerated in the prevention of chemotherapy-induced nausea and vomiting in patients with solid tumors undergoing moderately emetogenic chemotherapy or highly emetogenic chemotherapy. NEPA offers maximal convenience, and as a simple guideline-based regimen, has the potential to improve adherence to guidelines.

  4. Pharmacokinetic interaction study of a fixed combination of 500 mg acetylsalicylic acid/30 mg pseudoephedrine versus each of the single active ingredients in healthy male volunteers.

    Science.gov (United States)

    Lücker, Peter Wolfgang; Birkel, Manfred; Hey, Bernhard; Loose, Irene; Schaefer, Andrea

    2003-01-01

    Acetylsalicylic acid (CAS 50-78-2, ASA) and pseudoephedrine (CAS 90-82-4, PSE) both are remedies given together for the treatment of the symptoms of a common cold, i.e. mainly nasal congestion, running nose, sore throat and headache. The aim of this open, randomized, three-factorial (three-treatment, three-period, six-sequence) Latin Square clinical study was to investigate if there were any pharmacokinetic interactions between ASA and PSE when given as fixed combination of 500 mg ASA/30 mg PSE.HCl. Lack of interaction was assessed by determination of pharmacokinetic characteristics and relative bioavailability of both substances and salicylic acid (CAS 69-72-7, SA), administered in combination and as equally single dosed drugs. In total, the data of 12 healthy male volunteers were included into the pharmacokinetic evaluation. Primary target parameters were ratios combination/equally dosed single drugs of AUCnorm and Cmax, norm of ASA, its metabolite SA and PSE. The primary target parameters were analyzed using an analysis of variance (ANOVA) after logarithmic transformation of the data. 90% confidence intervals were calculated for the geometric means of ratios using the mean square error term of the ANOVA. Bioequivalence was given for AUCnorm and Cmax, norm for all ratios calculated. No interaction was found for AUCnorm and Cmax, norm between the fixed combination ASA/PSE and the equally single dosed drugs as reference. The supplementary evaluation for the non-normalized original parameters AUC and Cmax also revealed bioequivalence. All treatments were safe and well tolerated.

  5. 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.

  6. Newcastle disease virus, rituximab, and doxorubicin combination as anti-hematological malignancy therapy

    Directory of Open Access Journals (Sweden)

    Al-Shammari AM

    2016-04-01

    Full Text Available Ahmed Majeed Al-Shammari,1 Huda Rameez,2 Maha F Al-Taee2 1Department of Experimental Therapy, Iraqi Center for Cancer and Medical Genetic Research, Mustansiriyah University, 2Department of Biotechnology, College of Science, Baghdad University, Baghdad, IraqAbstract: Hematological malignancies are important diseases that need more powerful therapeutics. Even with current targeting therapies, such as rituximab and other chemotherapeutic agents, there is a need to develop new treatment strategies. Combination therapy seems the best option to target the tumor cells by different mechanisms. Virotherapy is a very promising treatment modality, as it is selective, safe, and causes cancer destruction. The Iraqi strain of Newcastle disease virus (NDV has proved to be effective both in vitro and in vivo. In the current work, we tested its ability on anti-hematological tumors and enhanced current treatments with combination therapy, and studied this combination using Chou–Talalay analysis. p53 concentration was measured to evaluate the mechanism of this proposed synergism. The results showed that NDV was synergistic with doxorubicin in low doses on plasmacytoma cells, with no involvement of p53 pathways, but involved p53 when the combination was used on non-Hodgkin lymphoma cells. NDV in combination with rituximab showed enhanced cytotoxicity that was p53-independent. In conclusion, this work proposes a novel combination modality for treatment of some hematological malignancies.Keywords: oncolytic viruses, virotherapy, combination therapy

  7. A Review of NEPA, a Novel Fixed Antiemetic Combination with the Potential for Enhancing Guideline Adherence and Improving Control of Chemotherapy-Induced Nausea and Vomiting.

    Science.gov (United States)

    Hesketh, Paul J; Aapro, Matti; Jordan, Karin; Schwartzberg, Lee; Bosnjak, Snezana; Rugo, Hope

    2015-01-01

    Combination antiemetic regimens targeting multiple molecular pathways associated with emesis have become the standard of care for prevention of chemotherapy-induced nausea and vomiting (CINV) related to highly and moderately emetogenic chemotherapies. Antiemetic consensus guidelines from several professional societies are widely available and updated regularly as new data emerges. Unfortunately, despite substantial research supporting the notion that guideline conformity improves CINV control, adherence to antiemetic guidelines is unsatisfactory. While studies are needed to identify specific barriers to guideline use and explore measures to enhance adherence, a novel approach has been taken to improve clinician adherence and patient compliance, with the development of a new combination antiemetic. NEPA is an oral fixed combination of a new highly selective NK1 receptor antagonist (RA), netupitant, and the pharmacologically and clinically distinct 5-HT3 RA, palonosetron. This convenient antiemetic combination offers guideline-consistent prophylaxis by targeting two critical pathways associated with CINV in a single oral dose administered only once per cycle. This paper will review and discuss the NEPA data in the context of how this first combination antiemetic may overcome some of the barriers interfering with adherence to antiemetic guidelines, enhance patient compliance, and offer a possible advance in the prevention of CINV for patients.

  8. A Review of NEPA, a Novel Fixed Antiemetic Combination with the Potential for Enhancing Guideline Adherence and Improving Control of Chemotherapy-Induced Nausea and Vomiting

    Directory of Open Access Journals (Sweden)

    Paul J. Hesketh

    2015-01-01

    Full Text Available Combination antiemetic regimens targeting multiple molecular pathways associated with emesis have become the standard of care for prevention of chemotherapy-induced nausea and vomiting (CINV related to highly and moderately emetogenic chemotherapies. Antiemetic consensus guidelines from several professional societies are widely available and updated regularly as new data emerges. Unfortunately, despite substantial research supporting the notion that guideline conformity improves CINV control, adherence to antiemetic guidelines is unsatisfactory. While studies are needed to identify specific barriers to guideline use and explore measures to enhance adherence, a novel approach has been taken to improve clinician adherence and patient compliance, with the development of a new combination antiemetic. NEPA is an oral fixed combination of a new highly selective NK1 receptor antagonist (RA, netupitant, and the pharmacologically and clinically distinct 5-HT3 RA, palonosetron. This convenient antiemetic combination offers guideline-consistent prophylaxis by targeting two critical pathways associated with CINV in a single oral dose administered only once per cycle. This paper will review and discuss the NEPA data in the context of how this first combination antiemetic may overcome some of the barriers interfering with adherence to antiemetic guidelines, enhance patient compliance, and offer a possible advance in the prevention of CINV for patients.

  9. Combination approaches with immune checkpoint blockade in cancer therapy

    Directory of Open Access Journals (Sweden)

    Maarten Swart

    2016-11-01

    Full Text Available In healthy individuals, immune checkpoint molecules prevent autoimmune responses and limit immune cell-mediated tissue damage. Tumors frequently exploit these molecules to evade eradication by the immune system. Over the past years, immune checkpoint blockade of cytotoxic T lymphocyte antigen-4 (CTLA-4 and programmed death-1 (PD-1 emerged as promising strategies to activate anti-tumor cytotoxic T cell responses. Although complete regression and long-term survival is achieved in some patients, not all patients respond. This review describes promising, novel combination approaches involving immune checkpoint blockade, aimed at increasing response-rates to the single treatments.

  10. Successful Therapy of Severe Pseudomembranous Clostridium difficile Colitis Using a Combination of Fecal Microbiota Therapy and Fidaxomicin

    Science.gov (United States)

    Konturek, Peter C.; Haziri, Drilon; Helfritzsch, Harry; Hess, Thomas; Harsch, Igor A.

    2017-01-01

    Objective The aim of this work was to describe the use of a combination of fidaxomicin and fecal microbiota therapy (FMT) in Clostridium difficile infection (CDI). Clinical Presentation and Intervention A 78-year-old female, who was admitted for surgery due to acute diverticulitis caused by postoperative complications and broad antibiotic therapy, developed CDI-induced colitis. Despite the introduction of metronidazole and vancomycin therapy, her clinical condition continued to deteriorate. She was transferred to the intensive care unit where FMT followed by fidaxomicin were performed because her C-reactive protein and leucocyte levels remained elevated. Further clinical improvement and the resolution of colitis was observed. Conclusion In this case, severe CDI colitis was successfully treated with the combination of FMT and fidaxomicin. PMID:27978522

  11. Successful Therapy of Severe Pseudomembranous Clostridium difficile Colitis Using a Combination of Fecal Microbiota Therapy and Fidaxomicin.

    Science.gov (United States)

    Konturek, Peter C; Haziri, Drilon; Helfritzsch, Harry; Hess, Thomas; Harsch, Igor A

    2017-01-01

    The aim of this work was to describe the use of a combination of fidaxomicin and fecal microbiota therapy (FMT) in Clostridium difficile infection (CDI). A 78-year-old female, who was admitted for surgery due to acute diverticulitis caused by postoperative complications and broad antibiotic therapy, developed CDI-induced colitis. Despite the introduction of metronidazole and vancomycin therapy, her clinical condition continued to deteriorate. She was transferred to the intensive care unit where FMT followed by fidaxomicin were performed because her C-reactive protein and leucocyte levels remained elevated. Further clinical improvement and the resolution of colitis was observed. In this case, severe CDI colitis was successfully treated with the combination of FMT and fidaxomicin. © 2016 S. Karger AG, Basel.

  12. Visually augmented targeted combination light therapy for acne vulgaris: a case report.

    Science.gov (United States)

    Yazdi, Alireza; Lyons, Colin-William; Roberts, Niamh

    2017-10-31

    Acne vulgaris is a common skin disease. Pharmacological modalities for treatment are proven to be efficacious but have limitations. Light therapy for acne vulgaris has shown promise in previous studies. This case report and its accompanying images show how a novel approach of visually augmented high fluence light therapy has been used to good effect. A 26-year-old Caucasian woman with acne vulgaris resistant to treatment with topical therapy underwent three sessions of combination potassium titanyl phosphate laser (532 nm)/neodymium-doped: yttrium aluminum garnet laser (1064 nm) light therapy with visually augmented narrow spot size and high fluence. A 73% reduction in total inflammatory lesions was evident 6 months after the initial treatment. This case report illustrates that there may be utility in this novel approach of narrow spot size, magnification-assisted, high fluence targeted combination laser therapy for inflammatory acne.

  13. Cost and appropriateness of treating asthma with fixed-combination drugs in local health care units in Italy

    Science.gov (United States)

    Ruggeri, Isabella; Bragato, Donatello; Colombo, Giorgio L; Valla, Emanuela; Di Matteo, Sergio

    2012-01-01

    Background Bronchial asthma is a chronic airways disease and is considered to be one of the major health problems in the Western world. During the last decade, a significant increase in the use of β2-agonists in combination with inhaled corticosteroids has been observed. The aim of this study was to assess the appropriateness of expenditure on these agents in an asthmatic population treated in a real practice setting. Methods This study used data for a resident population of 635,906 citizens in the integrated patient database (Banca Dati Assistito) of a local health care unit (Milano 2 Azienda Sanitaria Locale) in the Lombardy region over 3 years (2007–2009). The sample included 3787–4808 patients selected from all citizens aged ≥ 18 years entitled to social security benefits, having a prescription for a corticosteroid + β2-agonist combination, and an ATC code corresponding to R03AK, divided into three groups, ie, pressurized (spray) drugs, inhaled powders, and extrafine formulations. Patients with chronic obstructive lung disease were excluded. Indicators of appropriateness were 1–3 packs per year (underdosed, inappropriate), 4–12 packs per year (presumably appropriate), and ≥13 packs per year (overtreatment, inappropriate). Results The corticosteroid + β2-agonist combination per treated asthmatic patient increased from 37% in 2007 to 45% in 2009 for the total of prescribed antiasthma drugs, and 28%–32% of patients used the drugs in an appropriate manner (4–12 packs per years). The cost of inappropriately used packs increased combination drug expenditure by about 40%, leading to inefficient use of health care resources. This trend improved during the 3-year observation period. The mean annual cost per patient was higher for powders (€223.95) and sprays (€224.83) than for extrafine formulation (€142.71). Conclusion Based on this analysis, we suggest implementation of better health care planning and more appropriate prescription practices

  14. Oxidative stress in malaria and artemisinin combination therapy: Pros and Cons

    NARCIS (Netherlands)

    Kavishe, R.A.; Koenderink, J.B.; Alifrangis, M.

    2017-01-01

    Artemisinin-based combination therapy (ACT) has been adopted as a strategy to mitigate multidrug resistance to antimalarial monotherapies. ACT combines the rapid and effective but rather short plasma half-life antimalarial action of an artemisinin derivative with a longer acting partner drug.

  15. [Current optimization of combined therapy for chronic obstructive pulmonary disease].

    Science.gov (United States)

    Popova, E N

    2015-01-01

    Testing the new combined bronchodilator Anoro Ellipta in different clinical trials gives to its high clinical efficacy and safety in chronic obstructive pulmonary disease. The drug contains the molecules of sustained-release selective β2-adrenergic receptor agonist (vilanterol) and a muscarinic cholinergic receptor antagonist (umeclidinium bromide). The bronchodilating mechanisms of umeclidinium bromide are in the competitive inhibition of the binding of acetylcholine with muscarinic acetylcholine receptors of airway smooth muscles whereas in those of vilanterol are in that with the stimulation of intracellular adenylate cyclase. On days 1 and 24 after inhalation of the first dose of vilanterol and umeclidinium bromide, there was a significant increase in the forced expiratory volume in one second as compared to placebo. No clinical effects on QT interval on an electrocardiogram and cardiac rhythm were found. The benefits of an inhalation device (Ellipta) are its innovation design ensuring the effective delivery of an aerosol dose into the airway, convenience, and simplicity.

  16. Combined Immune Therapy for the Treatment of Visceral Leishmaniasis.

    Directory of Open Access Journals (Sweden)

    Rebecca J Faleiro

    2016-02-01

    Full Text Available Chronic disease caused by infections, cancer or autoimmunity can result in profound immune suppression. Immunoregulatory networks are established to prevent tissue damage caused by inflammation. Although these immune checkpoints preserve tissue function, they allow pathogens and tumors to persist, and even expand. Immune checkpoint blockade has recently been successfully employed to treat cancer. This strategy modulates immunoregulatory mechanisms to allow host immune cells to kill or control tumors. However, the utility of this approach for controlling established infections has not been extensively investigated. Here, we examined the potential of modulating glucocorticoid-induced TNF receptor-related protein (GITR on T cells to improve anti-parasitic immunity in blood and spleen tissue from visceral leishmaniasis (VL patients infected with Leishmania donovani. We found little effect on parasite growth or parasite-specific IFNγ production. However, this treatment reversed the improved anti-parasitic immunity achieved by IL-10 signaling blockade. Further investigations using an experimental VL model caused by infection of C57BL/6 mice with L. donovani revealed that this negative effect was prominent in the liver, dependent on parasite burden and associated with an accumulation of Th1 cells expressing high levels of KLRG-1. Nevertheless, combined anti-IL-10 and anti-GITR mAb treatment could improve anti-parasitic immunity when used with sub-optimal doses of anti-parasitic drug. However, additional studies with VL patient samples indicated that targeting GITR had no overall benefit over IL-10 signaling blockade alone at improving anti-parasitic immune responses, even with drug treatment cover. These findings identify several important factors that influence the effectiveness of immune modulation, including parasite burden, target tissue and the use of anti-parasitic drug. Critically, these results also highlight potential negative effects of

  17. Combination Therapy With and Without Tumor Necrosis Factor Inhibitors in Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Graudal, Niels; Hubeck-Graudal, Thorbjørn; Faurschou, Mikkel

    2015-01-01

    the effects of combination DMARD therapies with and without biologic agents as therapy for patients with RA. METHODS: Eight randomized controlled trials published in 10 articles were selected from a systematic literature search of 1,674 identified studies and integrated in a meta-analysis. These trials...... compared combinations of DMARDs versus a tumor necrosis factor (TNF) inhibitor plus methotrexate. Two reviewers independently entered data into standardized extraction forms. The combined effect measures were compared by means of the inverse variance method (continuous data) and the Mantel-Haenszel method...

  18. 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.

  19. FIRST EXPERIENCE OF CYMEVEN IN THE COMBINED THERAPY OF RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    R M Balabanova

    2001-01-01

    Full Text Available Ummary Objective. To reveal J'reguency of accompaning virus infection and possibility to use antivirus therapy together in therapy RA. Material. 40 patients with RA at the age of 17-45 were studied. The duration of disease was not more than 6 months; patients had 2-3 degrees of activity. Every one had a positive rheumatoid factor. Results. 78,2% of the examined patients connected the beginning of the illness with virus infection they have had. The most difficalt variant of RA course and uneffectiveness of basic therapy were registerd among the patients with combination HSV and CMV infection. Inclusion of Cymevene in complex therapy RA has exerted positive influence on clinical-laboratory, signs stregthened effect of basic therapy. Conclusion. The most difficult variant of RA course was registered among the patients with virus infection. Inclusion of antivirus drugs had a positive influence on effectiveness of basic therapy.

  20. Dosage dependent hormonal counter regulation to combination therapy in patients with left ventricular dysfunction

    DEFF Research Database (Denmark)

    Galløe, A.M.; Skagen, K.; Christensen, Niels Juel

    2006-01-01

    The present study attempts to assess the efficacy combination therapy for heart failure. Genuine dose-response studies on combination therapy are not available and published studies involved adding one drug on top of 'usual treatment'. Sixteen different dosage combinations of trandolapril...... with the maximal effect at 0.5 mg daily. Both drugs significantly increased renin concentration with a significant potentiating interaction. It was not possible to detect beneficial effects of combination therapies. The optimal dosage of Bumetanide appeared to be 0.5 mg twice daily based on its effect on quality...... of life and weight loss. Estimated by the reduction in systolic blood pressure the optimal dosage of Trandolapril appeared to be 0.5 mg once daily. CONCLUSIONS: It appears that patients should be given less than the usually recommended dosages. Patients may be treated with a low dose loop diuretic...

  1. Combination therapy with the type II anti-CD20 antibody obinutuzumab.

    Science.gov (United States)

    Klein, Christian; Bacac, Marina; Umana, Pablo; Fingerle-Rowson, Günter

    2017-10-01

    Obinutuzumab is a novel humanized type II glycoengineered anti-CD20 antibody approved for first-line treatment of chronic lymphocytic leukemia (CLL) in combination with chlorambucil and for treatment of rituximab-refractory follicular lymphoma (FL). Areas covered: We describe current preclinical and clinical evidence supporting the combination of obinutuzumab with not only chemotherapy but also novel targeted therapies for B-cell hematologic malignancies, and its application in chemoimmunotherapy. We also provide an overview of the current clinical trial landscape investigating novel combination therapies based on obinutuzumab. Expert opinion: Within the next 10 years the treatment of B-cell malignancies with obinutuzumab is expected to increasingly move towards chemotherapy-free regimens. Novel combinations of obinutuzumab will be explored with targeted therapies, antibody-drug conjugates, and/or other immunotherapeutic agents, with the aim to achieve clinically meaningful improvements in efficacy and patient safety.

  2. Improvement of cancer immunotherapy by combining molecular targeted therapy

    Directory of Open Access Journals (Sweden)

    Yutaka eKawakami

    2013-05-01

    Full Text Available In human cancer cells, a constitutive activation of MAPK, STAT3, β-catenin, and various other signaling pathways triggers multiple immunosuppressive cascades. These cascades result in the production of immunosuppressive molecules (e.g. TGF-β, IL-10, IL-6, VEGF, and CCL2 and induction of immunosuppressive immune cells (e.g. regulatory T cells, tolerogenic dendritic cells, and myeloid derived suppressor cells. Consequently, immunosuppressive conditions are formed in tumor-associated microenvironments, including the tumor and sentinel lymph nodes. Some of these cancer-derived cytokines and chemokines impair immune cells and render them immunosuppressive via the activation of signaling molecules, such as STAT3, in the immune cells. Thus, administration of signal inhibitors may inhibit the multiple immunosuppressive cascades by acting simultaneously on both cancer and immune cells at the key regulatory points in the cancer-immune network. Since common signaling pathways are involved in manifestation of several hallmarks of cancer, including cancer cell proliferation/survival, invasion/metastasis, and immunosuppression, targeting these shared signaling pathways in combination with immunotherapy may be a promising strategy for cancer treatment.

  3. Phase II study of bevacizumab and temsirolimus combination therapy for recurrent glioblastoma multiforme

    DEFF Research Database (Denmark)

    Lassen, Ulrik; Sorensen, Morten; Gaziel, Tine Bernhardtsen

    2013-01-01

    BACKGROUND: Bevacizumab combined with chemotherapy has recently shown promising efficacy in recurrent high-grade glioma. Phosphatase and tensin homolog (PTEN) mutation in glioblastoma multiforme (GBM) patients causes abnormally high activity of the pathways of Phosphatidylinositide 3-kinases (PI3K....../10), infection (1/10), hypertension (1/10), and hyperglycemia (1/10). CONCLUSION: Temsirolimus can be safely administered in combination with bevacizumab. This study failed to detect activity of such a combination in patients with progressive GBM beyond bevacizumab therapy....

  4. Effect of Clark's twin-block appliance (CTB and non-extraction fixed mechano-therapy on the pharyngeal dimensions of growing children

    Directory of Open Access Journals (Sweden)

    Batool Ali

    2015-12-01

    Full Text Available Abstract Introduction: Narrow airway dimensions due to mandibular deficiency can predispose an individual to severe respiratory distress. Hence, treatment with mandibular advancement devices at an early age might help improving the pharyngeal passage and reduce the risk of respiratory difficulties. Therefore, the aim of the current study was to evaluate the mean changes in the pharyngeal dimensions of children with mandibular deficiency treated with Clark's twin-block appliance (CTB followed by fixed orthodontic treatment. Methods: Orthodontic records of 42 children with mandibular deficiency were selected. Records comprised three lateral cephalograms taken at the start of CTB treatment, after CTB removal and at the end of fixed appliance treatment, and were compared with 32 controls from the Bolton-Brush study. Friedman test was used to compare pre-treatment, mid-treatment and post-treatment pharyngeal dimensions. Wilcoxon signed rank test was used to compare the airway between pre-treatment and post follow-up controls. Mann-Whitney U test was applied to compare the mean changes in pharyngeal dimensions between treatment group and controls from T2 to T0. Post-hoc Dunnet T3 test was used for multiple comparisons of treatment outcomes after CTB and fixed appliances, taking a p-value of ≤ 0.05 as statistically significant. Results: Superior pharyngeal space (p < 0.001 and upper airway thickness (p = 0.035 were significantly increased after CTB, and the change in superior pharyngeal space remained stable after fixed mechano-therapy. Conclusion: CTB can have a positive effect in improving pharyngeal space and the resultant increase in airway remains stable on an average of two and a half years.

  5. Combining fixed effects and instrumental variable approaches for estimating the effect of psychosocial job quality on mental health: evidence from 13 waves of a nationally representative cohort study.

    Science.gov (United States)

    Milner, Allison; Aitken, Zoe; Kavanagh, Anne; LaMontagne, Anthony D; Pega, Frank; Petrie, Dennis

    2017-06-23

    Previous studies suggest that poor psychosocial job quality is a risk factor for mental health problems, but they use conventional regression analytic methods that cannot rule out reverse causation, unmeasured time-invariant confounding and reporting bias. This study combines two quasi-experimental approaches to improve causal inference by better accounting for these biases: (i) linear fixed effects regression analysis and (ii) linear instrumental variable analysis. We extract 13 annual waves of national cohort data including 13 260 working-age (18-64 years) employees. The exposure variable is self-reported level of psychosocial job quality. The instruments used are two common workplace entitlements. The outcome variable is the Mental Health Inventory (MHI-5). We adjust for measured time-varying confounders. In the fixed effects regression analysis adjusted for time-varying confounders, a 1-point increase in psychosocial job quality is associated with a 1.28-point improvement in mental health on the MHI-5 scale (95% CI: 1.17, 1.40; P instrumental variable analysis, a 1-point increase psychosocial job quality is related to 1.62-point improvement on the MHI-5 scale (95% CI: -0.24, 3.48; P = 0.088). Our quasi-experimental results provide evidence to confirm job stressors as risk factors for mental ill health using methods that improve causal inference.

  6. Nanostructured lipid carriers of artemether-lumefantrine combination for intravenous therapy of cerebral malaria.

    Science.gov (United States)

    Prabhu, Priyanka; Suryavanshi, Shital; Pathak, Sulabha; Patra, Aditya; Sharma, Shobhona; Patravale, Vandana

    2016-11-20

    Patients with cerebral malaria (CM) are unable to take oral medication due to impaired consciousness and vomiting thus necessitating parenteral therapy. Quinine, artemether, and artesunate which are currently used for parenteral malaria therapy have their own drawbacks. The World Health Organization (WHO) has now banned monotherapy and recommends artemisinin-based combination therapy for malaria treatment. However, presently there is no intravenous formulation available for combination therapy of malaria. Artemether-Lumefantrine (ARM-LFN) is a WHO approved combination for oral malaria therapy. However, the low aqueous solubility of ARM and LFN hinders their intravenous delivery. The objective of this study was to formulate ARM-LFN nanostructured lipid carriers (NLC) for intravenous therapy of CM. ARM-LFN NLC were prepared by microemulsion template technique and characterized for size, drug content, entrapment efficiency, drug release, crystallinity, morphology, amenability to autoclaving, compatibility with infusion fluids, stability, antimalarial efficacy in mice, and toxicity in rats. The ARM-LFN NLC showed sustained drug release, amenability to autoclaving, compatibility with infusion fluids, good stability, complete parasite clearance and reversal of CM symptoms with 100% survival in Plasmodium berghei-infected mice, and safety in rats. The biocompatible ARM-LFN NLC fabricated by an industrially feasible technique offer a promising solution for intravenous therapy of CM. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Recent Advances in Upconversion Nanoparticles-Based Multifunctional Nanocomposites for Combined Cancer Therapy.

    Science.gov (United States)

    Tian, Gan; Zhang, Xiao; Gu, Zhanjun; Zhao, Yuliang

    2015-12-16

    Lanthanide-doped upconversion nanoparticles (UCNPs) have the ability to generate ultraviolet or visible emissions under continuous-wave near-infrared (NIR) excitation. Utilizing this special luminescence property, UCNPs are approved as a new generation of contrast agents in optical imaging with deep tissue-penetration ability and high signal-to-noise ratio. The integration of UCNPs with other functional moieties can endow them with highly enriched functionalities for imaging-guided cancer therapy, which makes composites based on UCNPs emerge as a new class of theranostic agents in biomedicine. Here, recent progress in combined cancer therapy using functional nanocomposites based on UCNPs is reviewed. Combined therapy referring to the co-delivery of two or more therapeutic agents or a combination of different treatments is becoming more popular in clinical treatment of cancer because it generates synergistic anti-cancer effects, reduces individual drug-related toxicity and suppresses multi-drug resistance through different mechanisms of action. Here, the recent advances of combined therapy contributed by UCNPs-based nanocomposites on two main branches are reviewed: i) photodynamic therapy and ii) chemotherapy, which are the two most widely adopted therapies of UCNPs-based composites. The future prospects and challenges in this emerging field will be also discussed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Effectiveness of standardized combination therapy for migraine treatment in the pediatric emergency department.

    Science.gov (United States)

    Leung, Stephanie; Bulloch, Blake; Young, Christine; Yonker, Marcy; Hostetler, Mark

    2013-03-01

    To compare outcomes of pediatric migraine patients treated in an emergency department (ED) before and after implementation of a standardized combination intravenous therapy regimen aimed toward improving and standardizing abortive migraine therapy. In a pediatric ED, migraines represent 8-18% of all headache visits. Despite this large number, no standard treatment for acute migraine therapy currently exists. The study utilized a retrospective chart review of patients seeking acute migraine treatment at a tertiary care, pediatric ED from August 2006 to March 2010. Inclusion criteria were pediatric migraine patients as defined by International Headache Society guidelines. The comparison population received various migraine therapies based on attending practice preference. After October 2008, patients received standardized intravenous combination therapy involving a normal saline fluid bolus, ketorolac, prochlorperazine, and diphenhydramine. Occasionally, metoclopramide was substituted during prochlorperazine shortages. Reduction in headache pain score was the primary outcome. Secondary outcome measures included length of ED stay, hospital admission rate, and ED readmission rate within 48 hours. The study yielded 87 patients who received standardized combination therapy and 165 comparison patients. No significant difference in patient characteristics existed when evaluating patient demographics, outpatient medication use, and initial headache pain score. When compared with the non-standardized therapy population, the combination therapy patients revealed significant reductions in pain score (decrease of 5.3 vs. 6.9, difference -1.6, 95% confidence interval -2.2 to -0.8, P pediatric migraine therapy in the ED by significantly reducing headache pain scores, length of ED stay, and hospital admission rates. © 2013 American Headache Society.

  9. Design of a Dissolving Microneedle Platform for Transdermal Delivery of a Fixed-Dose Combination of Cardiovascular Drugs.

    Science.gov (United States)

    Quinn, Helen L; Bonham, Louise; Hughes, Carmel M; Donnelly, Ryan F

    2015-10-01

    Microneedles (MNs) are a minimally invasive drug delivery platform, designed to enhance transdermal drug delivery by breaching the stratum corneum. For the first time, this study describes the simultaneous delivery of a combination of three drugs using a dissolving polymeric MN system. In the present study, aspirin, lisinopril dihydrate, and atorvastatin calcium trihydrate were used as exemplar cardiovascular drugs and formulated into MN arrays using two biocompatible polymers, poly(vinylpyrrollidone) and poly(methylvinylether/maleic acid). Following fabrication, dissolution, mechanical testing, and determination of drug recovery from the MN arrays, in vitro drug delivery studies were undertaken, followed by HPLC analysis. All three drugs were successfully delivered in vitro across neonatal porcine skin, with similar permeation profiles achieved from both polymer formulations. An average of 126.3 ± 18.1 μg of atorvastatin calcium trihydrate was delivered, notably lower than the 687.9 ± 101.3 μg of lisinopril and 3924 ± 1011 μg of aspirin, because of the hydrophobic nature of the atorvastatin molecule and hence poor dissolution from the array. Polymer deposition into the skin may be an issue with repeat application of such a MN array, hence future work will consider more appropriate MN systems for continuous use, alongside tailoring delivery to less hydrophilic compounds. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  10. Fixed Points

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 5; Issue 5. Fixed Points - From Russia with Love - A Primer of Fixed Point Theory. A K Vijaykumar. Book Review Volume 5 Issue 5 May 2000 pp 101-102. Fulltext. Click here to view fulltext PDF. Permanent link:

  11. Combined Antirelapse Therapy in Patients with Schizoaffective Disorder: A Prospective Cohort Study

    Directory of Open Access Journals (Sweden)

    Zhanna R. Gardanova

    2016-06-01

    Full Text Available Background: In most studies, patients with schizoaffective disorder (SAD are often combined into one group along with schizophrenia patients or less commonly with those suffering from affective disorders, which makes it difficult to obtain data about the peculiarities of SAD treatment. Articles dedicated to SAD treatment in the interictal period are rare. Methods and Results: The prospective cohort study was conducted from 2011 to 2015. The study involved 86 patients diagnosed with SAD according to ICD-10. Patients received neuroleptics (NLs as antirelapse therapy for 2 years (NL therapy; then mood stabilizers (MSs were added to the antirelapse treatment (NL+MS therapy. The results of this combined therapy with MSs were evaluated after 2 years of treatment. Our results suggest that the use of combination therapy that includes antipsychotics and MSs leads to maintenance of a higher quality remission. Remission becomes more prolonged and affective swings less pronounced, resulting in improved quality of life in SAD patients. Improving the quality of remission can be attributed to the following characteristics of the combined therapy: a the use of lower doses of neuroleptics; b a reduction in the frequency and severity of mood swings; and c an increase in patient compliance. Conclusion: The use of combined pharmacotherapy including antipsychotics and MSs produces a longer, high-quality remission. The inclusion of MSs in the scheme of treatment increases the patient adherence to a medication regimen. The use of MSs in combination therapy reduces affective fluctuations, thereby increasing the probability of maintaining remission with complete symptom relief.

  12. Combined anti-tumor necrosis factor-α therapy and DMARD therapy in rheumatoid arthritis patients reduces inflammatory gene expression in whole blood compared to DMARD therapy alone

    Directory of Open Access Journals (Sweden)

    Carl K Edwards

    2012-12-01

    Full Text Available Periodic assessment of gene expression for diagnosis and monitoring in rheumatoid arthritis (RA may provide a readily available and useful method to detect subclinical disease progression and follow responses to therapy with disease modifying anti-rheumatic agents (DMARDs or anti-TNF-α therapy. We used quantitative real-time PCR to compare peripheral blood gene expression profiles in active ("unstable" RA patients on DMARDs, stable RA patients on DMARDs, and stable RA patients treated with a combination of a DMARD and an anti-TNF-α agent (infliximab or etanercept to healthy human controls. The expression of 48 inflammatory genes were compared between healthy controls (N=122, unstable DMARD patients (N=18, stable DMARD patients (N=26, and stable patients on combination therapy (N=20. Expression of 13 genes was very low or undetectable in all study groups. Compared to healthy controls, patients with unstable RA on DMARDs exhibited increased expression of 25 genes, stable DMARD patients exhibited increased expression of 14 genes and decreased expression of five genes, and combined therapy patients exhibited increased expression of six genes and decreased expression of 10 genes. These findings demonstrate that active RA is associated with increased expression of circulating inflammatory markers whereas increases in inflammatory gene expression are diminished in patients with stable disease on either DMARD or anti-TNF-α therapy. Furthermore, combination DMARD and anti-TNF-α therapy is associated with greater reductions in circulating inflammatory gene expression compared to DMARD therapy alone. These results suggest that assessment of peripheral blood gene expression may prove useful to monitor disease progression and response to therapy.

  13. Review of extended-release niacin/laropiprant fixed combination in the treatment of mixed dyslipidemia and primary hypercholesterolemia

    Directory of Open Access Journals (Sweden)

    Klaus G Parhofer

    2009-11-01

    Full Text Available Klaus G ParhoferMedical Department II Grosshadern, University of Munich, GermanyAbstract: Although statins reduce cardiovascular morbidity and mortality further risk reduction is needed. In this respect low HDL-cholesterol concentrations and/or elevated triglyceride concentrations may be potential treatment targets. Niacin (nicotinic acid is an effective drug which increases the plasma concentration of high-density lipoprotein (HDL-cholesterol and decreases the concentration of low-density lipoprotein (LDL-cholesterol, triglycerides and lipoprotein(a. Clinical studies indicate that niacin can significantly reduce the risk for cardiovascular events. However, niacin is not very commonly used because of significant side effects (especially flushing. Laropiprant is a potent selective antagonist of PGD2-receptor subtype-1 and can thus reduce niacin-induced flushing. Although the addition of laropiprant will reduce the frequency of flushing, it will not completely eliminate this side effect. Laropiprant does not change the effect of niacin on lipids or other side effects of niacin (ie, gastro-intestinal problems, glucose elevation. The combination of niacin with laropiprant may therefore enable use of niacin at higher doses and therefore exploit the full potential of the drug. Endpoint studies that will be published over the next few years will show whether this treatment modality also translates into clinical effect in patients treated with statins. Until publication of these studies niacin/laropiprant should be used only in high-risk patients not achieving lipid goals on statins.Keywords: nicotinic acid, flushing, hyperlipidemia, dyslipoproteinemia 

  14. Clinical study on the influence of a fixed-dose combination of famotidine with calcium carbonate and magnesium hydroxide on the bioavailability of famotidine.

    Science.gov (United States)

    Zhai, Qing; Fu, Jun; Huang, Xia; Xu, Bin; Yuan, Yao-Zong; Jiang, Tao; Rong, Zheng-Xing; Chen, Hong-Zhuan

    2008-01-01

    The potential interaction of the H2-receptor antagonist famotidine (CAS 76824-35-6) with calcium carbonate (CAS 471-34-1) and magnesium hydroxide (CAS 1309-42-8) during administration of the famotidine fixed dose combination (FDC) formulation was investigated. A randomized, open-label, two-period, crossover study was carried out on 12 healthy Chinese volunteers. Plasma concentration-time profiles of famotidine were similar with the FDC formulation and common formulation. Confidence interval (90% CI) for maximal concentration (C(max)) and area under the curve (AUC(o-t)) of famoti-dine were 94.8-112.2% and 94.2-112.3%, respectively. These findings suggest that calcium carbonate/magnesium hydroxide antacids have no significant effects on famotidine pharmacokinetics when they are administered together with famotidine as an FDC formulation.

  15. A Fixed Ratio Combination of Insulin Degludec and Liraglutide (IDegLira) Reduces Glycemic Fluctuation and Brings More Patients with Type 2 Diabetes Within Blood Glucose Target Ranges

    DEFF Research Database (Denmark)

    King, Allen B; Philis-Tsimikas, Athena; Kilpatrick, Eric S

    2017-01-01

    BACKGROUND: Reducing glycemic fluctuation is important for optimal diabetes management. This post hoc analysis examined glycemic fluctuations and the proportion of subjects achieving recommended blood glucose targets with the fixed ratio combination of insulin degludec and liraglutide (IDeg......Lira) compared to insulin degludec (IDeg) and liraglutide alone. METHODS: We analyzed nine-point self-monitored blood glucose (SMBG) profiles from two randomized trials involving IDegLira in patients with type 2 diabetes (T2D), and continuous glucose monitoring (CGM) data from a subset of patients in one......). IDegLira also resulted in a greater reduction in the range of SMBG values over 24 h than IDeg (P ≤ 0.0001). CGM data showed that IDegLira provided greater reductions in interstitial glucose (IG) fluctuation (P = 0.0018) and postprandial IG increment (P = 0.0288) compared with IDeg. Compared...

  16. 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

  17. Use and effectiveness of a fixed-ratio combination of insulin degludec/liraglutide (IDegLira) in a real-world population with type 2 diabetes: Results from a European, multicentre, retrospective chart review study.

    Science.gov (United States)

    Price, Hermione; Blüher, Matthias; Prager, Rudolf; Phan, Tra-Mi; Thorsted, Brian L; Schultes, Bernd

    2017-12-05

    To describe the real-world use and effectiveness of IDegLira, a fixed-ratio combination of the basal insulin degludec, and the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide. This European, multicentre, retrospective chart review comprised adults (n = 611) with type 2 diabetes, who started IDegLira ≥6 months before data collection. Clinical characteristics were assessed at baseline (defined as the most recent recording during the 6 months before the first IDegLira prescription) and 3, 6, 9 and 12 months (± 45 days for each time point) after commencing IDegLira, where data were available. Baseline regimens included non-injectable medications (19%), basal insulin (19%), GLP-1RA (10%), free combination therapy (insulin/GLP-1RA, 24%) and multiple daily-dose insulin injections (MDI, 28%), all ± oral antidiabetic drugs. After 6 months, significant glycated haemoglobin (HbA1c) reductions were observed in patients overall and in all subgroups (-10 mmol/mol [-0.9%] overall; P world practice, after 6 months and at a moderate dose, IDegLira resulted in substantial reductions in HbA1c and body weight, with a reduced risk of hypoglycaemia. © 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

  18. Symptomatic treatment of the common cold with a fixed-dose combination of paracetamol, chlorphenamine and phenylephrine: a randomized, placebo-controlled trial.

    Science.gov (United States)

    Picon, Paulo Dornelles; Costa, Marisa Boff; da Veiga Picon, Rafael; Fendt, Lucia Costa Cabral; Suksteris, Maurício Leichter; Saccilotto, Indara Carmanim; Dornelles, Alicia Dorneles; Schmidt, Luis Felipe Carissimi

    2013-11-22

    The common cold and other viral airway infections are highly prevalent in the population, and their treatment often requires the use of medications for symptomatic relief. Paracetamol is as an analgesic and antipyretic; chlorphenamine is an antihistamine; and phenylephrine, a vasoconstrictor and decongestant. This randomized, double-blind, placebo-controlled trial sought to evaluate the efficacy and safety of a fixed-dose combination of paracetamol, chlorphenamine and phenylephrine in the symptomatic treatment of the common cold and flu-like syndrome in adults. This study enrolled 146 individuals aged 18 to 60 years who had moderate to severe flu-like syndrome or common cold. After clinical examination and laboratory tests, individuals were randomly assigned to receive the fixed-dose combination (73) or placebo (73), five capsules per day for 48 to 72 hours. The primary efficacy endpoint was the sum of the scores of 10 symptoms on a four-point Likert-type scale. To evaluate treatment safety, the occurrence of adverse events was also measured. Mean age was 33.5 (±9.5) years in the placebo group and 33.8 (±11.5) in the treatment group. There were 55 women and 18 men in the placebo group, and 46 women and 27 men in the treatment group. Comparison of overall symptom scores in the two groups revealed a significantly greater reduction in the treatment group than in the placebo group (p = 0.015). Analysis at the first 13 dose intervals (± 66 h of treatment) showed a greater reduction of symptom scores in the treatment group than in the placebo group (p paracetamol, chlorphenamine and phenylephrine was safe and more effective than placebo in the symptomatic treatment of the common cold or flu-like syndrome in adults. NCT01389518.

  19. Combined Effects of CO2 and Light on the N2-Fixing Cyanobacterium Trichodesmium IMS101: Physiological Responses1[OA

    Science.gov (United States)

    Kranz, Sven A.; Levitan, Orly; Richter, Klaus-Uwe; Prášil, Ondřej; Berman-Frank, Ilana; Rost, Björn

    2010-01-01

    Recent studies on the diazotrophic cyanobacterium Trichodesmium erythraeum (IMS101) showed that increasing CO2 partial pressure (pCO2) enhances N2 fixation and growth. Significant uncertainties remain as to the degree of the sensitivity to pCO2, its modification by other environmental factors, and underlying processes causing these responses. To address these questions, we examined the responses of Trichodesmium IMS101 grown under a matrix of low and high levels of pCO2 (150 and 900 μatm) and irradiance (50 and 200 μmol photons m−2 s−1). Growth rates as well as cellular carbon and nitrogen contents increased with increasing pCO2 and light levels in the cultures. The pCO2-dependent stimulation in organic carbon and nitrogen production was highest under low light. High pCO2 stimulated rates of N2 fixation and prolonged the duration, while high light affected maximum rates only. Gross photosynthesis increased with light but did not change with pCO2. HCO3− was identified as the predominant carbon source taken up in all treatments. Inorganic carbon uptake increased with light, but only gross CO2 uptake was enhanced under high pCO2. A comparison between carbon fluxes in vivo and those derived from 13C fractionation indicates high internal carbon cycling, especially in the low-pCO2 treatment under high light. Light-dependent oxygen uptake was only detected under low pCO2 combined with high light or when low-light-acclimated cells were exposed to high light, indicating that the Mehler reaction functions also as a photoprotective mechanism in Trichodesmium. Our data confirm the pronounced pCO2 effect on N2 fixation and growth in Trichodesmium and further show a strong modulation of these effects by light intensity. We attribute these responses to changes in the allocation of photosynthetic energy between carbon acquisition and the assimilation of carbon and nitrogen under elevated pCO2. These findings are supported by a complementary study looking at photosynthetic

  20. Blood Pressure and Cholesterol-lowering Efficacy of a Fixed-dose Combination With Irbesartan and Atorvastatin in Patients With Hypertension and Hypercholesterolemia: A Randomized, Double-blind, Factorial, Multicenter Phase III Study.

    Science.gov (United States)

    Kim, Sang-Hyun; Jo, Sang-Ho; Lee, Sang-Cheol; Lee, Sung-Yoon; Yoon, Myung-Ho; Lee, Hyang-Lim; Lee, Nae-Hee; Ha, Jong-Won; Lee, Nam-Ho; Kim, Dong-Woon; Han, Gyu-Rok; Hyon, Min-Su; Cho, Deok-Gyu; Park, Chang-Gyu; Kim, Young-Dae; Ryu, Gyu-Hyung; Kim, Cheol-Ho; Kim, Kee-Sik; Chung, Myung-Ho; Chae, Sung-Chul; Seung, Ki-Bae; Oh, Byung-Hee

    2016-10-01

    A fixed-dose combination of a stain and an antihypertensive drug may be useful for the treatment of patients with hypertension and hyperlipidemia. It may also improve patient drug compliance to help control risk factors of cardiovascular disease. This study was designed to evaluate the blood pressure-lowering and cholesterol-lowering effect of a fixed-dose combination of irbesartan-atorvastatin compared with monotherapy by either agent over an 8-week treatment period. Patients with comorbid hypertension and hypercholesterolemia were screened for this randomized, double-blind, Phase III study. Eligible study patients were randomly assigned to test groups receiving a combination of irbesartan 300 mg and atorvastatin 40 mg or 80 mg (IRB300 + ATO40 and IRB300 + ATO80). Comparator groups comprised monotherapy groups with irbesartan 300 mg (IRB300) or atorvastatin 40 mg (ATO40) or atorvastatin 80 mg (ATO80), or placebo. Patients who were eligible at screening were subjected to a 4- to 6-week washout period before commencing 8 weeks of therapy per their assigned group. The primary efficacy end points were percent change in LDL-C and sitting diastolic blood pressure (DBP) levels from baseline to end of therapy. Tolerability profiles of combination therapy were compared with other groups. A total of 733 patients with comorbid hypertension and hypercholesterolemia were screened for this study; 230 eligible patients were randomized to treatment. The mean age of patients was 58.9 (8.5) years, and their mean body mass index was 25.8 (3.2) kg/m2. More than two thirds (70.9%) of the study patients were male. Mean LDL-C and sitting DBP levels at baseline were 149.54 (29.19) mg/dL and 92.32 (6.03) mm Hg, respectively. Percent reductions in LDL-C after 8 weeks were 46.74% (2.06%) in the IRB300 + ATO40 group and 48.98% (2.12%) in the IRB300 + ATO80 group; these values were 47.13% (3.21%) and 48.30% (2.98%) in the ATO40 and ATO80 comparator groups. Similarly, a reduction in sitting

  1. [Clinical trial of a combination of three drugs in fixed proportions in the treatment of tuberculosis. Groupe de Travail sur la Chimiothérapie de la Tuberculose].

    Science.gov (United States)

    Chaulet, P; Boulahbal, F

    1995-10-01

    The Matiben Chest Clinic at the West Algiers University Teaching Hospital, and 3 outpatient clinics specializing in tuberculosis and lung disease in Algiers. To determine the tolerance and efficacy of a fixed proportion combination of 3 antituberculosis drugs (per tablet: 50 mg isoniazid + 120 mg rifampicin + 300 mg pyrazinamide) given during the first 2 months of a daily 6-month chemotherapy regimen. Random prospective treatment trial comparing a group of 124 patients receiving the triple combination with another group of 126 patients receiving the 3 drugs separately during the initial treatment phase. The continuation phase was identical for the 2 groups. Comparison of tolerance in the first 2 months, and of the failure and relapse rates (respectively at the end of treatment and 24 months after the end of treatment). During the first 2 months side-effects were significantly more common in the group receiving the drugs separately. At the end of treatment and during the following 24 months there were no significant differences in the cumulative rates of observed failures and relapses (2% and 1%). The triple combination studied could replace the separate drugs in the initial treatment phase in countries where the bioavailability of the drugs used has been proven.

  2. COMBINATION THERAPY OF HYPERTENSION — A RELIABLE WAY TO TARGET ACHIEVE

    Directory of Open Access Journals (Sweden)

    Yu. V. Lukina

    2010-01-01

    Full Text Available Data of evidence-based cardiology and clinical guidelines that define the position of combined therapy to achieve the targets of hypertension (HT treatment (achievement and maintenance of the target blood pressure (BP level, protection of the target organs, improvement of the quality of life in hypertensive patients are presented in the article. The advantages of rational combined therapies (potentiation of antihypertensive effect, reduction of a number of adverse events are considered. Studies of therapeutic efficacy and safety of combined antihypertensive therapy based on generics are important. The advantages of combined therapy in achievement of target BP levels are presented on example of comparative study of new generic and original amlodipine in patients with HT of 1-2 degrees. Target BP level was reached respectively in 90% and 97% of patients with HT in groups of generic and original amlodipine combined with generic lisinopril and hydrochlorothiazide. Safety profile was acceptable. This confirms the high efficacy of amlodipine + lisinopril + hydrochlorothiazide combination, including one on the basis of generics.

  3. Pharmacokinetics of the evogliptin/metformin extended-release (5/1,000 mg fixed-dose combination formulation compared to the corresponding loose combination, and food effect in healthy subjects

    Directory of Open Access Journals (Sweden)

    Rhee SJ

    2016-04-01

    Full Text Available Su-jin Rhee,1,* SeungHwan Lee,1,2,* Seo Hyun Yoon,1 Joo-Youn Cho,1 In-Jin Jang,1 Kyung-Sang Yu1 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, 2Clinical Trials Center, Seoul National University Hospital, Seoul, Republic of Korea *These authors contributed equally to this work Abstract: A new fixed-dose combination formulation of evogliptin 5 mg and metformin extended-release (XR 1,000 mg (FDC_EVO5/MET1000 was developed to improve medication adherence for type 2 diabetes mellitus. The pharmacokinetics of FDC_EVO5/MET1000 was compared to the corresponding loose combination in a randomized, open-label, crossover study in 36 healthy male subjects (Part 1, and the food effect on FDC_EVO5/MET1000 was assessed (under fasted or fed conditions in a randomized, open-label, crossover study in 28 healthy male subjects (Part 2. Serial blood samples for pharmacokinetic analysis were collected up to 72 hours, and pharmacokinetic parameters of evogliptin and metformin were calculated using non-compartmental methods. The geometric mean ratios (fixed-dose combination to loose combination and 90% confidence intervals of pharmacokinetic parameters for evogliptin and metformin were all within 0.800–1.250, suggesting bioequivalent pharmacokinetic. After a single oral dose of FDC_EVO5/MET1000, food did not significantly affect evogliptin pharmacokinetic while systemic exposure of metformin was increased about 47.5% under the fed condition, which is consistent with the already established food effect on metformin XR. FDC_EVO5/MET1000 was generally well tolerated without any drug-related serious adverse events. In conclusion, FDC_EVO5/MET1000 can be substituted for the loose combination of FDC_EVO5/MET1000, providing better compliance with convenient administration. Keywords: pharmacokinetics, bioequivalence, food effect, fixed-dose combination, evogliptin, metformin XR

  4. Review of dutasteride/tamsulosin fixed-dose combination for the treatment of benign prostatic hyperplasia: efficacy, safety, and patient acceptability

    Directory of Open Access Journals (Sweden)

    Barkin J

    2011-10-01

    Full Text Available Jack BarkinHumber River Regional Hospital, Toronto, Canada and Department of Surgery, University of Toronto, Toronto, Ontario, CanadaAbstract: Lower urinary tract symptoms (LUTS caused by benign prostatic hyperplasia (BPH will usually affect older men, of whom 50% over the age 60 years and almost 90% in their nineties will be bothered enough by their symptoms that they request some type of treatment. However, symptomatic bother may also affect men in their forties with a prevalence rate of almost 18%. The International Prostate Symptom Score (IPSS has become the most widely used and best validated questionnaire to allow the patient to quantify the severity of his LUTS/BPH symptoms. This score has become the cornerstone in demonstrating the “rate of symptom response” for the patient who has been exposed to any type BPH management. Question 8 on the IPSS score is what is defined as the “Quality of Life” question or what is also termed the “Bothersome Index.” The score out of 6 as declared by the patient will reflect the degree of concern that the patient is feeling about his symptoms and the reduction of the score after treatment is a statement of their improved quality of life. There are 2 families of accepted medical therapy to treat the symptoms of BPH and potentially prevent the most worrisome long-term sequelae of progression of BPH: urinary retention or the need for surgery. When defining the impact of the main types of medical therapy, the alpha blockers have been termed the “openers” and the 5 alpha-reductase inhibitors are described as the “shrinkers.” Since they each offer a different mechanism of effect, the concept of combination therapy was raised and trialed many times over recent years. The final aspect of any medical therapy is the patient's satisfaction with the treatment and the side effects. In the CombAT (Combination of Avodart and Tamsulosin trial a new assessment was developed and tested called the Patient

  5. Fixing the Mirrors: A Feasibility Study of the Effects of Dance Movement Therapy on Young Adults with Autism Spectrum Disorder

    Science.gov (United States)

    Koch, Sabine C.; Mehl, Laura; Sobanski, Esther; Sieber, Maik; Fuchs, Thomas

    2015-01-01

    From the 1970s on, case studies reported the effectiveness of therapeutic mirroring in movement with children with autism spectrum disorder. In this feasibility study, we tested a dance movement therapy intervention based on mirroring in movement in a population of 31 young adults with autism spectrum disorder (mainly high-functioning and…

  6. [Effect of cyclosporine and simulect mono and combination therapy on cardiac allo-transplantation in rats].

    Science.gov (United States)

    Xiong, Hai-Bo; Xia, Sui-Sheng; Huang, Zu-Fal; Ye, Qi-Fa; Wen, Hao

    2005-10-01

    To observe the effect of cyclosporine and simulect mono or combination therapy on cardiac allo-transplantation in rats. Recipients with allografts were treated with different doses of cyclosporine and/or simulect after cardiac allo-transplantation. Graft survival time was observed; the histopathological examination of graft tissues was performed; and levels of serum IL-2 and IL-4 were determined. Mono or combination therapy with cyclosporine and/or simulect increased the survival of cardiac allografts. With the prolongation of survival time of the grafts, the rejection of grafts was moderated. The serum IL-2 level increased in acute rejected grafts; the serum IL-4 level increased evidently in long survival grafts. Cyclosporine and simulect have an effect in the prolongation of cardiac allograft survival in rats, and the combination therapy shows an evident synergistic effect.

  7. Effect of a fixed combination of nimodipine and betahistine versus betahistine as monotherapy in the long-term treatment of Ménière's disease: a 10-year experience.

    Science.gov (United States)

    Monzani, D; Barillari, M R; Alicandri Ciufelli, M; Aggazzotti Cavazza, E; Neri, V; Presutti, L; Genovese, E

    2012-12-01

    Despite an abundance of long-term pharmacological treatments for recurrent vertigo attacks due to Ménière's disease, there is no general agreement on the their efficacy. We present the results of a retrospective study based on a 10-year experience with two long-term medical protocols prescribed to patients affected by Ménière's disease (diagnosed according to the American Academy of Otolaryngology-Head and Neck Surgery Committee on Hearing and Equilibrium guidelines) who completed treatments in the period 1999-2009. A total of 113 medical records were analysed; 53 patients received betahistine-dihydrochloride at on-label dosage (32 mg die) for six months, and 60 patients were treated with the same regimen and nimodipine (40 mg die) as an add-therapy during the same period. Nimodipine, a 1,4-dihydropyridine that selectively blocks L-type voltage-sensitive calcium channels, has previously been tested as a monotherapy for recurrent vertigo of labyrinthine origin in a multinational, double-blind study with positive results. A moderate reduction of the impact of vertigo on quality of life (as assessed by the Dizziness Handicap Inventory) was obtained in patients after therapy with betahistine (p 0.05), whereas the fixed combination of betahistine and nimodipine was associated with a significant reduction of tinnitus annoyance and improvement of hearing loss (p nimodipine represents not only a valid add-therapy for Ménière's disease, and that it may also exert a specific effect on inner ear disorders. Further studies to investigate this possibility are needed.

  8. HIV-1 CCR5 gene therapy will fail unless it is combined with a suicide gene.

    Science.gov (United States)

    Pandit, Aridaman; de Boer, Rob J

    2015-12-17

    Highly active antiretroviral therapy (ART) has successfully turned Human immunodeficiency virus type 1 (HIV-1) from a deadly pathogen into a manageable chronic infection. ART is a lifelong therapy which is both expensive and toxic, and HIV can become resistant to it. An alternative to lifelong ART is gene therapy that targets the CCR5 co-receptor and creates a population of genetically modified host cells that are less susceptible to viral infection. With generic mathematical models we show that gene therapy that only targets the CCR5 co-receptor fails to suppress HIV-1 (which is in agreement with current data). We predict that the same gene therapy can be markedly improved if it is combined with a suicide gene that is only expressed upon HIV-1 infection.

  9. The Potential for Cellular Therapy Combined with Growth Factors in Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Jack Rosner

    2012-01-01

    Full Text Available Any traumatic spinal cord injury (SCI may cause symptoms ranging from pain to complete loss of motor and sensory functions below the level of the injury. Currently, there are over 2 million SCI patients worldwide. The cost of their necessary continuing care creates a burden for the patient, their families, and society. Presently, few SCI treatments are available and none have facilitated neural regeneration and/or significant functional improvement. Research is being conducted in the following areas: pathophysiology, cellular therapies (Schwann cells, embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells, olfactory ensheathing cells, growth factors (BDNF, inhibitory molecules (NG2, myelin protein, and combination therapies (cell grafts and neurotrophins, cotransplantation. Results are often limited because of the inhibitory environment created following the injury and the limited regenerative potential of the central nervous system. Therapies that show promise in small animal models may not transfer to nonhuman primates and humans. None of the research has resulted in remarkable improvement, but many areas show promise. Studies have suggested that a combination of therapies may enhance results and may be more effective than a single therapy. This paper reviews and discusses the most promising new SCI research including combination therapies.

  10. Combination therapy of fexofenadine and montelukast is effective in prurigo nodularis and pemphigoid nodularis.

    Science.gov (United States)

    Shintani, Takako; Ohata, Chika; Koga, Hiroshi; Ohyama, Bungo; Hamada, Takahiro; Nakama, Takekuni; Furumura, Minao; Tsuruta, Daisuke; Ishii, Norito; Hashimoto, Takashi

    2014-01-01

    In this study, we report on the efficacy of combination therapy of second-generation antihistamine antagonist, fexofenadine hydrochloride, and leukotriene receptor inhibitor, montelukast sodium, for the treatment of 15 prurigo nodularis or pemphigoid nodularis patients, in whom conventional therapy was ineffective. All patients received 10 mg montelukast once a day and 240 mg fexofenadine twice a day for 4 weeks in addition to other medications they had been taking. We assessed the manifestations of the lesions and itching intensity before and after the therapy, and we evaluated each patient as (i) markedly improved, (ii) improved, (iii) slightly improved, (iv) no change, (v) worse. Two patients (13.3%) were evaluated as markedly improved, and the lesions of one patient completely disappeared. Three patients (20.0%) were evaluated as improved, and six patients (40.0%) as slightly improved. Thus, 11 of 15 cases (73.3%) improved by combination therapy of fexofenadine and montelukast, in which nine cases (75.0%) of prurigo nodularis and two cases (66.7%) of pemphigoid nodularis were involved. No patients revealed any side effects. This study revealed that combination therapy of fexofenadine and montelukast was effective for some patients with conventional therapy-resistant prurigo nodularis and pemphigoid nodularis. © 2013 Wiley Periodicals, Inc.

  11. Targeting the NF-κB Pathway as a Combination Therapy for Advanced Thyroid Cancer.

    Directory of Open Access Journals (Sweden)

    Nikita Pozdeyev

    Full Text Available NF-κB signaling plays an important role in tumor cell proliferation, cell survival, angiogenesis, invasion, metastasis and drug/radiation resistance. Combination therapy involving NF-κB pathway inhibition is an attractive strategy for the treatment of advanced forms of thyroid cancer. This study was designed to test the efficacy of NF-κB pathway inhibition in combination with cytotoxic chemotherapy, using docetaxel and ionizing radiation in in vitro models of thyroid cancer. We found that while both docetaxel and ionizing radiation activated NF-κB signaling in thyroid cancer cells, there was no synergistic effect on cell proliferation and/or programmed cell death with either genetic (transduction of a dominant negative mutant form of IκBα or pharmacologic (proteasome inhibitor bortezomib and IKKβ inhibitor GO-Y030 inhibition of the NF-κB pathway in thyroid cancer cell lines BCPAP, 8505C, THJ16T and SW1736. Docetaxel plus bortezomib synergistically decreased in vitro invasion of 8505C cells, but not in the other cell lines. Screening of a panel of clinically relevant targeted therapies for synergy with genetic NF-κB inhibition in a proliferation/cytotoxicity assay identified the histone deacetylase (HDAC inhibitor suberoylanilide hydroxamic acid (SAHA as a potential candidate. However, the synergistic effect was confirmed only in the BCPAP cells. These results indicate that NF-κB inhibitors are unlikely to be beneficial as combination therapy with taxane cytotoxic chemotherapy, external radiation therapy or radioiodine therapy. There may be unique circumstances where NF-κB inhibitors may be considered in combination with docetaxel to reduce tumor invasion or in combination with HDAC inhibitors to reduce tumor growth, but this does not appear to be a combination therapy that could be broadly applied to patients with advanced thyroid cancer. Further research may identify which subsets of patients/tumors may respond to this therapeutic

  12. Effects of combination therapy with captopril and nifedipine in severe or resistant hypertension.

    Science.gov (United States)

    White, W B; Viadero, J J; Lane, T J; Podesla, S

    1986-01-01

    To assess the effect of potent vasodilator therapy in patients with severe or resistant hypertension, 10 patients underwent therapy with captopril and nifedipine alone and in combination. Blood pressure (BP), heart rate, and blood chemistry values were monitored for 4 weeks during captopril monotherapy and after 8 weeks during combination therapy with captopril and nifedipine. Compared with baseline, the BP decreased during captopril monotherapy (180 +/- 11/98 +/- 7 vs. 209 +/- 16/118 +/- 12 mm Hg; P less than 0.005). After the addition of nifedipine, the BP was further reduced (148 +/- 23/85 +/- 16 mm Hg), but there was no change in heart rate. In three patients not achieving the diastolic BP goal during combination therapy with dosing every 8 hours, automatic 24-hour ambulatory BP monitoring demonstrated lack of antihypertensive control for only the last 2 to 3 hours of the dosing interval. These data demonstrate that combination therapy with captopril and nifedipine is effective in patients with severe hypertension, but frequent dosing intervals are necessary for adequate antihypertensive control.

  13. Combining kangaroo care and live harp music therapy in the neonatal intensive care unit setting.

    Science.gov (United States)

    Schlez, Ayelet; Litmanovitz, Ita; Bauer, Sofia; Dolfin, Tzipora; Regev, Rivka; Arnon, Shmuel

    2011-06-01

    Music therapy has been recommended as an adjuvant therapy for both preterm infants and mothers during their stay in the neonatal intensive care unit (NICU), and has been shown to have beneficial effects. To study the usefulness of combining live harp music therapy and kangaroo care (KC) on short-term physiological and behavioral parameters of preterm infants and their mothers in the NICU setting. Included in this study were stable infants born between 32 and 37 weeks of gestation, with normal hearing. Mother-infant dyads were randomly assigned to KC and live harp music therapy or to KC alone. Using repeated measures, neonatal and maternal heart rate, oxygen saturation and respiratory rate were recorded along with neonatal behavioral state and maternal anxiety state. Maternal age, ethnicity, education, and love of music were documented. Fifty-two mother-infant dyads were tested. Compared with KC alone, KC and live harp music therapy had a significantly beneficial effect on maternal anxiety score (46.8 +/- 10 vs. 27.7 +/- 7.1, respectively, P therapy is more beneficial in reducing maternal anxiety than KC alone. This combined therapy had no apparent effect on the tested infants' physiological responses or behavioral state.

  14. Feasibility Study Combining Art Therapy or Cognitive Remediation Therapy with Family-based Treatment for Adolescent Anorexia Nervosa.

    Science.gov (United States)

    Lock, James; Fitzpatrick, Kathleen Kara; Agras, William S; Weinbach, Noam; Jo, Booil

    2018-01-01

    Adolescents with anorexia nervosa who have obsessive-compulsive (OC) features respond poorly to family-based treatment (FBT). This study evaluated the feasibility of combining FBT with either cognitive remediation therapy (CRT) or art therapy (AT) to improve treatment response in this at-risk group. Thirty adolescents with anorexia nervosa and OC features were randomized to 15 sessions of FBT + CRT or AT. Recruitment rate was 1 per month, and treatment attrition was 16.6% with no differences between groups. Suitability, expectancy and therapeutic relationships were acceptable for both combinations. Correlations between changes in OC traits and changes in cognitive inefficiencies were found for both combinations. Moderate changes in cognitive inefficiencies were found in both groups but were larger in the FBT + AT combination. This study suggests that an RCT for poor responders to FBT because of OC traits combining FBT with either CRT or AT is feasible to conduct. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

  15. Effectiveness of β-Lactam Monotherapy vs Macrolide Combination Therapy for Children Hospitalized With Pneumonia.

    Science.gov (United States)

    Williams, Derek J; Edwards, Kathryn M; Self, Wesley H; Zhu, Yuwei; Arnold, Sandra R; McCullers, Jonathan A; Ampofo, Krow; Pavia, Andrew T; Anderson, Evan J; Hicks, Lauri A; Bramley, Anna M; Jain, Seema; Grijalva, Carlos G

    2017-12-01

    β-Lactam monotherapy and β-lactam plus macrolide combination therapy are both common empirical treatment strategies for children hospitalized with pneumonia, but few studies have evaluated the effectiveness of these 2 treatment approaches. To compare the effectiveness of β-lactam monotherapy vs β-lactam plus macrolide combination therapy among a cohort of children hospitalized with pneumonia. We analyzed data from the Etiology of Pneumonia in the Community Study, a multicenter, prospective, population-based study of community-acquired pneumonia hospitalizations conducted from January 1, 2010, to June 30, 2012, in 3 children's hospitals in Nashville, Tennessee; Memphis, Tennessee; and Salt Lake City, Utah. The study included all children (up to 18 years of age) who were hospitalized with radiographically confirmed pneumonia and who received β-lactam monotherapy or β-lactam plus macrolide combination therapy. Data analysis was completed in April 2017. We defined the referent as β-lactam monotherapy, including exclusive use of an oral or parenteral second- or third-generation cephalosporin, penicillin, ampicillin, ampicillin-sulbactam, amoxicillin, or amoxicillin-clavulanate. Use of a β-lactam plus an oral or parenteral macrolide (azithromycin or clarithromycin) served as the comparison group. We modeled the association between these groups and patients' length of stay using multivariable Cox proportional hazards regression. Covariates included demographic, clinical, and radiographic variables. We further evaluated length of stay in a cohort matched by propensity to receive combination therapy. Logistic regression was used to evaluate secondary outcomes in the unmatched cohort, including intensive care admission, rehospitalizations, and self-reported recovery at follow-up. Our study included 1418 children (693 girls and 725 boys) with a median age of 27 months (interquartile range, 12-69 months). This cohort was 60.1% of the 2358 children enrolled in the

  16. Photothermal therapy combined with dinitrophenyl hapten for the treatment of late stage malignant melanoma

    Science.gov (United States)

    Li, Xiaosong; Du, Nan; Li, Haijun; Long, Shan; Chen, Dianjun; Zhou, Feifan; Xu, Yuanyuan; Wang, Fuli; Chen, Wei R.

    2017-02-01

    To evaluate the efficacy and safety of photothermal with dinitrophenyl hapten (DNP) for patients with malignant melanoma (MM), Patients with pathology confirmed stage III or IV MM were enrolled. Seventy-two patients were randomized into two groups, DNP alone group (n=36) and DNP plus photothermal therapy group (n=36). The results showed that the patients in the combination treatment group had longer median progression-free survival time (19.0m vs. 12.0m, p=0.007). No severe adverse events were observed in both groups. Thus, the combination of photothermal therapy and DNP maybe a new therapeutic strategy for patients with advanced MM.

  17. Investigation of bioequivalence of a new fixed-dose combination of nifedipine and candesartan with the corresponding loose combination as well as the drug-drug interaction potential between both drugs under fasting conditions.

    Science.gov (United States)