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      Adverse Event Assessment of Antimuscarinics for Treating Overactive Bladder: A Network Meta-Analytic Approach

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          Abstract

          Background

          Overactive bladder (OAB) affects the lives of millions of people worldwide and antimuscarinics are the pharmacological treatment of choice. Meta-analyses of all currently used antimuscarinics for treating OAB found similar efficacy, making the choice dependent on their adverse event profiles. However, conventional meta-analyses often fail to quantify and compare adverse events across different drugs, dosages, formulations, and routes of administration. In addition, the assessment of the broad variety of adverse events is dissatisfying. Our aim was to compare adverse events of antimuscarinics using a network meta-analytic approach that overcomes shortcomings of conventional analyses.

          Methods

          Cochrane Incontinence Group Specialized Trials Register, previous systematic reviews, conference abstracts, book chapters, and reference lists of relevant articles were searched. Eligible studies included randomized controlled trials comparing at least one antimuscarinic for treating OAB with placebo or with another antimuscarinic, and adverse events as outcome measures. Two authors independently extracted data. A network meta-analytic approach was applied allowing for joint assessment of all adverse events of all currently used antimuscarinics while fully maintaining randomization.

          Results

          69 trials enrolling 26′229 patients were included. Similar overall adverse event profiles were found for darifenacin, fesoterodine, transdermal oxybutynin, propiverine, solifenacin, tolterodine, and trospium chloride but not for oxybutynin orally administered when currently used starting dosages were compared.

          Conclusions

          The proposed generally applicable transparent network meta-analytic approach summarizes adverse events in an easy to grasp way allowing straightforward benchmarking of antimuscarinics for treating OAB in clinical practice. Most currently used antimuscarinics seem to be equivalent first choice drugs to start the treatment of OAB except for oral oxybutynin dosages of ≥10 mg/d which may have more unfavorable adverse event profiles.

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          Most cited references79

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          Individual patient- versus group-level data meta-regressions for the investigation of treatment effect modifiers: ecological bias rears its ugly head.

          When performing a meta-analysis, interest often centres on finding explanations for heterogeneity in the data, rather than on producing a single summary estimate. Such exploratory analyses are frequently undertaken with published, study-level data, using techniques of meta-analytic regression. Our goal was to explore a real-world example for which both published, group-level and individual patient-level data were available, and to compare the substantive conclusions reached by both methods. We studied the benefits of anti-lymphocyte antibody induction therapy among renal transplant patients in five randomized trials, focusing on whether there are subgroups of patients in whom therapy might prove particularly beneficial. Allograft failure within 5 years was the endpoint studied. We used a variety of analytic approaches to the group-level data, including weighted least-squares regression (N=5 studies), logistic regression (N=628, the total number of subjects), and a hierarchical Bayesian approach. We fit logistic regression models to the patient-level data. In the patient-level analysis, we found that treatment was significantly more effective among patients with elevated (20 per cent or more) panel reactive antibodies (PRA) than among patients without elevated PRA. These patients comprise a small (about 15 per cent of patients) subgroup of patients that benefited from therapy. The group-level analyses failed to detect this interaction. We recommend using individual patient data, when feasible, to study patient characteristics, in order to avoid the potential for ecological bias introduced by group-level analyses. Copyright 2002 John Wiley & Sons, Ltd.
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            Overactive bladder significantly affects quality of life.

            Overactive bladder (OAB), with symptoms of frequency, urgency, and urge incontinence, substantially affects the lives of millions of people. The symptoms associated with OAB can significantly affect the social, psychological, occupational, domestic, physical, and sexual aspects of those who suffer from it. Unfortunately, many sufferers are reluctant to discuss their condition with their healthcare provider or family members. As a result, OAB remains underreported, despite increased awareness and improved diagnosis and treatment. Health-related quality of life can be measured objectively, and several instruments have been developed, validated, and used in research. Currently, there are 2 major types of quality-of-life questionnaires: generic and disease specific. Although these questionnaires have been helpful and are widely used, the goal is to establish a single questionnaire that is acceptable throughout the world for use by urologists, gynecologists, urogynecologists, geriatricians, and epidemiologists.
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              Tolterodine and tamsulosin for treatment of men with lower urinary tract symptoms and overactive bladder: a randomized controlled trial.

              Men with overactive bladder and other lower urinary tract symptoms may not respond to monotherapy with antimuscarinic agents or alpha-receptor antagonists. To evaluate the efficacy and safety of tolterodine extended release (ER), tamsulosin, or both in men who met research criteria for both overactive bladder and benign prostatic hyperplasia. Randomized, double-blind, placebo-controlled trial conducted at 95 urology clinics in the United States involving men 40 years or older who had a total International Prostate Symptom Score of 12 or higher and, an International Prostate Symptom Score quality-of-life (QOL) item score of 3 or higher, a self-rated bladder condition of at least moderate bother, and a bladder diary documenting micturition frequency (>or=8 micturitions per 24 hours) and urgency (>or=3 episodes per 24 hours), with or without urgency urinary incontinence. Patients were recruited between November 2004 and February 2006, and the study was completed May 2006. Patients were randomly assigned to receive placebo (n = 222), 4 mg of tolterodine ER (n = 217), 0.4 mg of tamsulosin (n = 215), or both tolterodine ER plus tamsulosin (n = 225) for 12 weeks. Patient perception of treatment benefit, bladder diary variables, International Prostate Symptom Scores, and safety and tolerability were assessed. A total of 172 men (80%) receiving tolterodine ER plus tamsulosin reported treatment benefit by week 12 compared with 132 patients (62%) receiving placebo (P<.001), 146 (71%) receiving tamsulosin (P=.06 vs placebo), or 135 (65%) receiving tolterodine ER (P=.48 vs placebo). Patients receiving tolterodine ER plus tamsulosin compared with placebo experienced significant reductions in urgency urinary incontinence (-0.88 vs -0.31, P=.005), urgency episodes without incontinence (-3.33 vs -2.54, P=.03), micturitions per 24 hours (-2.54 vs -1.41, P<.001), and micturitions per night (-0.59 vs -0.39, P.02). Patients receiving tolterodine ER plus tamsulosin demonstrated significant improvements on the total International Prostate Symptom Score (-8.02 vs placebo, -6.19, P=.003) and QOL item (-1.61 vs -1.17, P=.003). All interventions were well tolerated. The incidence of acute urinary retention requiring catheterization was low (tolterodine ER plus tamsulosin, 0.4%; tolterodine ER, 0.5%; tamsulosin, 0%; and placebo, 0%). These results suggest that treatment with tolterodine ER plus tamsulosin for 12 weeks provides benefit for men with moderate to severe lower urinary tract symptoms including overactive bladder. Clinical Trials Registration clinicaltrials.gov Identifier: NCT00147654.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2011
                23 February 2011
                : 6
                : 2
                : e16718
                Affiliations
                [1 ]Horten Centre for Patient Oriented Research, University of Zürich, Zürich, Switzerland
                [2 ]Neuro-Urology, Spinal Cord Injury Centre, Balgrist University Hospital, Zürich, Switzerland
                [3 ]Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada
                [4 ]Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre, Maastricht, The Netherlands
                Lerner Research Institute, Cleveland Clinic, United States of America
                Author notes

                Conceived and designed the experiments: TMK LMB. Performed the experiments: TMK DL MU. Analyzed the data: TMK LMB CM AGHK. Contributed reagents/materials/analysis tools: CM AGHK. Wrote the paper: TMK LMB AGHK. Critical revision of the manuscript for important intellectual content: CM DL MU HJS.

                Article
                PONE-D-10-03397
                10.1371/journal.pone.0016718
                3044140
                21373193
                62fb74d7-9a9b-4eed-a68c-f6de237d540a
                Kessler, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 11 October 2010
                : 23 December 2010
                Page count
                Pages: 1
                Categories
                Research Article
                Medicine
                Clinical Research Design
                Meta-Analyses
                Systematic Reviews
                Drugs and Devices
                Adverse Reactions
                Urology
                Bladder and Ureteric Disorders
                Female Urology
                Urodynamics

                Uncategorized
                Uncategorized

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