Jean Hay-Smith

Effectiveness of anticholinergic drugs compared with placebo in the treatment of overactive bladder: systematic review

Abstract Objective: To determine the effectiveness of anticholinergic drugs for the treatment of overactive bladder syndrome. Design: Systematic review of randomised controlled trials. Data sources: Published papers and abstracts. Study selection: Randomised controlled trials with anticholinergic drug treatment in one arm and placebo in another. Data extraction: Primary outcomes of interest were patient perceived cure or improvement in symptoms, differences in number of incontinent episodes and number of voids in 24 hours, and side effects. Secondary outcomes of interest were urodynamic measures of bladder function (volume at first contraction, maximum cystometric capacity, and residual volume) and adverse events. Data synthesis: 32 trials were included, totalling 6800 participants. Most trials were described as double blind but were variable in other aspects of quality. At the end of treatment, cure or improvement (relative risk 1.41, 95% confidence interval 1.29 to 1.54), differences in incontinent episodes in 24 hours (estimated mean difference 0.6, 0.4 to 0.8), number of voids in 24 hours (0.6, 0.4 to 0.8), maximum cystometric capacity (54 ml, 43 ml to 66 ml), and volume at first contraction (52 ml, 37 ml to 67 ml), were significantly in favour of anticholinergics (P<0.0001 for all). Anticholinergics were associated with significantly higher residual volumes (4 ml, 1 ml to 7 ml; P=0.02) and an increased rate of dry mouth (relative risk 2.56, 2.24 to 2.92; P<0.0001). Sensitivity analysis, although affected by small numbers of studies, showed little likelihood of an effect of age, sex, diagnosis, or choice of drug. Conclusions: Although statistically significant, the differences between anticholinergic drugs and placebo were small, apart from the increased rate of dry mouth in patients receiving active treatment. For many of the outcomes studied, the observed difference between anticholinergics and placebo may be of questionable clinical significance. None of these studies provided data on long term outcome. What is already known on this topic Anticholinergics are the first line medical treatment for overactive bladder The effectiveness of these drugs is unclear What this study adds Anticholinergics produce significant improvements in overactive bladder symptoms compared with placebo The benefits are, however, of limited clinical significance

Systematic review and economic modelling of the effectiveness and cost-effectiveness of non-surgical treatments for women with stress urinary incontinence.

OBJECTIVES To assess the clinical effectiveness and cost-effectiveness of non-surgical treatments for women with stress urinary incontinence (SUI) through systematic review and economic modelling. DATA SOURCES The Cochrane Incontinence Group Specialised Register, electronic databases and the websites of relevant professional organisations and manufacturers, and the following databases: CINAHL, EMBASE, BIOSIS, Science Citation Index and Social Science Citation Index, Current Controlled Trials, ClinicalTrials.gov and the UKCRN Portfolio Database. STUDY SELECTION The study comprised three distinct elements. (1) A survey of 188 women with SUI to identify outcomes of importance to them (activities of daily living; sex, hygiene and lifestyle issues; emotional health; and the availability of services). (2) A systematic review and meta-analysis of non-surgical treatments for SUI to find out which are most effective by comparing results of trials (direct pairwise comparisons) and by modelling results (mixed-treatment comparisons - MTCs). A total of 88 randomised controlled trials (RCTs) and quasi-RCTs reporting data from 9721 women were identified, considering five generic interventions [pelvic floor muscle training (PFMT), electrical stimulation (ES), vaginal cones (VCs), bladder training (BT) and serotonin-noradrenaline reuptake inhibitor (SNRI) medications], in many variations and combinations. Data were available for 37 interventions and 68 treatment comparisons by direct pairwise assessment. Mixed-treatment comparison models compared 14 interventions, using data from 55 trials (6608 women). (3) Economic modelling, using a Markov model, to find out which combinations of treatments (treatment pathways) are most cost-effective for SUI. DATA EXTRACTION Titles and abstracts identified were assessed by one reviewer and full-text copies of all potentially relevant reports independently assessed by two reviewers. Any disagreements were resolved by consensus or arbitration by a third person. RESULTS Direct pairwise comparison and MTC analysis showed that the treatments were more effective than no treatment. Delivering PFMT in a more intense fashion, either through extra sessions or with biofeedback (BF), appeared to be the most effective treatment [PFMT extra sessions vs no treatment (NT) odds ratio (OR) 10.7, 95% credible interval (CrI) 5.03 to 26.2; PFMT + BF vs NT OR 12.3, 95% CrI 5.35 to 32.7]. Only when success was measured in terms of improvement was there evidence that basic PFMT was better than no treatment (PFMT basic vs NT OR 4.47, 95% CrI 2.03 to 11.9). Analysis of cost-effectiveness showed that for cure rates, the strategy using lifestyle changes and PFMT with extra sessions followed by tension-free vaginal tape (TVT) (lifestyle advice-PFMT extra sessions-TVT) had a probability of greater than 70% of being considered cost-effective for all threshold values for willingness to pay for a QALY up to 50,000 pounds. For improvement rates, lifestyle advice-PFMT extra sessions-TVT had a probability of greater than 50% of being considered cost-effective when societys willingness to pay for an additional QALY was more than 10,000 pounds. The results were most sensitive to changes in the long-term performance of PFMT and also in the relative effectiveness of basic PFMT and PFMT with extra sessions. LIMITATIONS Although a large number of studies were identified, few data were available for most comparisons and long-term data were sparse. Challenges for evidence synthesis were the lack of consensus on the most appropriate method for assessing incontinence and intervention protocols that were complex and varied considerably across studies. CONCLUSIONS More intensive forms of PFMT appear worthwhile, but further research is required to define an optimal form of more intensive therapy that is feasible and efficient for the NHS to provide, along with further definitive evidence from large, well-designed studies.

Pelvic floor muscle training versus no treatment, or inactive control treatments, for urinary incontinence in women: A short version Cochrane systematic review with meta‐analysis

Pelvic floor muscle training (PFMT) is a commonly used physical therapy for women with urinary incontinence (UI).

Consensus on Exercise Reporting Template (CERT): Modified Delphi Study.

Background Exercise interventions are often incompletely described in reports of clinical trials, hampering evaluation of results and replication and implementation into practice. Objective The aim of this study was to develop a standardized method for reporting exercise programs in clinical trials: the Consensus on Exercise Reporting Template (CERT). Design and Methods Using the EQUATOR Networks methodological framework, 137 exercise experts were invited to participate in a Delphi consensus study. A list of 41 items was identified from a meta-epidemiologic study of 73 systematic reviews of exercise. For each item, participants indicated agreement on an 11-point rating scale. Consensus for item inclusion was defined a priori as greater than 70% agreement of respondents rating an item 7 or above. Three sequential rounds of anonymous online questionnaires and a Delphi workshop were used. Results There were 57 (response rate=42%), 54 (response rate=95%), and 49 (response rate=91%) respondents to rounds 1 through 3, respectively, from 11 countries and a range of disciplines. In round 1, 2 items were excluded; 24 items reached consensus for inclusion (8 items accepted in original format), and 16 items were revised in response to participant suggestions. Of 14 items in round 2, 3 were excluded, 11 reached consensus for inclusion (4 items accepted in original format), and 7 were reworded. Sixteen items were included in round 3, and all items reached greater than 70% consensus for inclusion. Limitations The views of included Delphi panelists may differ from those of experts who declined participation and may not fully represent the views of all exercise experts. Conclusions The CERT, a 16-item checklist developed by an international panel of exercise experts, is designed to improve the reporting of exercise programs in all evaluative study designs and contains 7 categories: materials, provider, delivery, location, dosage, tailoring, and compliance. The CERT will encourage transparency, improve trial interpretation and replication, and facilitate implementation of effective exercise interventions into practice.

Meta-analyses of small numbers of trials often agree with longer-term results.

OBJECTIVE Many systematic reviews include only a few studies. It is unclear whether recommendations based on these will be correct in the longer term; hence, this article explores whether meta-analyses give reliable results after only a few studies. STUDY DESIGN AND SETTING Cumulative meta-analysis of data from 65 meta-analyses from 18 Cochrane systematic reviews was carried out. Various measures of closeness to the pooled estimate from all trials after three and five trials were included. Changes during the accumulation of evidence were noted. RESULTS The 95% confidence interval included the final estimate in 72% of meta-analyses after three studies and in 83% after five studies. It took a median of four (interquartile range: 1.25-6) studies to get within 10% of the final point estimate. Agreement between the results at three and five studies and the final estimate was not predicted by the number of participants, the number of events, τ(2), or I(2). Estimates could still change substantially after many trials were included. CONCLUSION Many of the conclusions drawn from systematic reviews with small numbers of included studies will be correct in the long run, but it is not possible to predict which ones.

Research priorities in urinary incontinence: results from citizens’ juries

Objective  The objective of this study was to elicit research ideas, priorities and outcome measures from women who suffer from urinary incontinence.

2014 consensus statement on improving pelvic floor muscle training adherence: International Continence Society 2011 State-of-the-Science Seminar.

To summarize the findings and “expert‐panel” consensus of the State‐of‐the‐Science Seminar on pelvic floor muscle training (PFMT) adherence held prior to the 41st International Continence Society scientific meeting, Glasgow, 2011.

Pelvic‐floor‐muscle‐training adherence “modifiers”: A review of primary qualitative studies—2011 ICS State‐of‐the‐Science Seminar research paper III of IV

This review aims to locate and summarize the findings of qualitative studies exploring the experience of and adherence to pelvic floor muscle training (PFMT) to recommend future directions for practice and research.

Pelvic floor muscle training for secondary prevention of pelvic organ prolapse (PREVPROL): a multicentre randomised controlled trial

BACKGROUND Pelvic floor muscle training can reduce prolapse severity and symptoms in women seeking treatment. We aimed to assess whether this intervention could also be effective in secondary prevention of prolapse and the need for future treatment. METHODS We did this multicentre, parallel-group, randomised controlled trial at three centres in New Zealand and the UK. Women from a longitudinal study of pelvic floor function after childbirth were potentially eligible for inclusion. Women of any age who had stage 1-3 prolapse, but had not sought treatment, were randomly assigned (1:1), via remote computer allocation, to receive either one-to-one pelvic floor muscle training (five physiotherapy appointments over 16 weeks, and annual review) plus Pilates-based pelvic floor muscle training classes and a DVD for home use (intervention group), or a prolapse lifestyle advice leaflet (control group). Randomisation was minimised by centre, parity (three or less vs more than three deliveries), prolapse stage (above the hymen vs at or beyond the hymen), and delivery method (any vaginal vs all caesarean sections). Women and intervention physiotherapists could not be masked to group allocation, but allocation was masked from data entry researchers and from the trial statistician until after database lock. The primary outcome was self-reported prolapse symptoms (Pelvic Organ Prolapse Symptom Score [POP-SS]) at 2 years. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01171846. FINDINGS Between Dec 21, 2008, and Feb 24, 2010, in New Zealand, and Oct 27, 2010, and Sept 5, 2011, in the UK, we randomly assigned 414 women to the intervention group (n=207) or the control group (n=207). One participant in each group was excluded after randomisation, leaving 412 women for analysis. At baseline, 399 (97%) women had prolapse above or at the level of the hymen. The mean POP-SS score at 2 years was 3·2 (SD 3·4) in the intervention group versus 4·2 (SD 4·4) in the control group (adjusted mean difference -1·01, 95% CI -1·70 to -0·33; p=0·004). The mean symptom score stayed similar across time points in the control group, but decreased in the intervention group. Three adverse events were reported, all of which were in the intervention group (one women had a fall, one woman had a pain in her tail bone, and one woman had chest pain and shortness of breath). INTERPRETATION Our study shows that pelvic floor muscle training leads to a small, but probably important, reduction in prolapse symptoms. This finding will be important for women and caregivers considering preventive strategies. FUNDING Wellbeing of Women charity, the New Zealand Continence Association, and the Deans Bequest Fund of Dunedin School of Medicine.

Pelvic‐Floor‐Muscle Training Adherence: Tools, Measurements and Strategies—2011 ICS State‐of‐the‐Science Seminar Research Paper II of IV

This paper on pelvic‐floor‐muscle training (PFMT) adherence, the second of four from the International Continence Societys 2011 State‐of‐the‐Science Conference, aims to (1) identify and collate current adherence outcome measures, (2) report the determinants of adherence, (3) report on PFMT adherence strategies, and (4) make actionable clinical and research recommendations.