scholarly journals Clinical effectiveness and cost-effectiveness of surgical options for the management of anterior and/or posterior vaginal wall prolapse: two randomised controlled trials within a comprehensive cohort study – results from the PROSPECT Study

2016 ◽  
Vol 20 (95) ◽  
pp. 1-452 ◽  
Author(s):  
Cathryn Glazener ◽  
Suzanne Breeman ◽  
Andrew Elders ◽  
Christine Hemming ◽  
Kevin Cooper ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Adverse Effects ◽  
Clinical Effectiveness ◽  
Prolapse Surgery ◽  
Controlled Trials ◽  
Complication Rates ◽  
Biological Graft ◽  
Randomised Controlled

BackgroundThe use of mesh in prolapse surgery is controversial, leading to a number of enquiries into its safety and efficacy.ObjectiveTo compare synthetic non-absorbable mesh inlay, biological graft and mesh kit with a standard repair in terms of clinical effectiveness, adverse effects, quality of life (QoL), costs and cost-effectiveness.DesignTwo randomised controlled trials within a comprehensive cohort (CC) study. Allocation was by a remote web-based randomisation system in a 1 :1 : 1 ratio (Primary trial) or 1 : 1 : 2 ratio (Secondary trial), and was minimised on age, type of prolapse repair planned, need for a concomitant continence procedure, need for a concomitant upper vaginal prolapse procedure and surgeon. Participants and outcome assessors were blinded to randomisation; participants were unblinded if they requested the information. Surgeons were not blinded to allocated procedure.SettingThirty-five UK hospitals.ParticipantsPrimary study: 2474 women in the analysis (including 1348 randomised) having primary anterior or posterior prolapse surgery.Secondary study: 398 in the analysis (including 154 randomised) having repeat anterior or posterior prolapse surgery.CC3: 215 women having either uterine or vault prolapse repair.InterventionsAnterior or posterior repair alone, or with mesh inlay, biological graft or mesh kit.Main outcome measuresProlapse symptoms [Pelvic Organ Prolapse Symptom Score (POP-SS)]; prolapse-specific QoL; cost-effectiveness [incremental cost per quality-adjusted life-year (QALY)].ResultsPrimary trials: adjusting for baseline and minimisation covariates, mean POP-SS was similar for each comparison {standard 5.4 [standard deviation (SD) 5.5] vs. mesh 5.5 (SD 5.1), mean difference (MD) 0.00, 95% confidence interval (CI) –0.70 to 0.71; standard 5.5 (SD 5.6) vs. graft 5.6 (SD 5.6), MD –0.15, 95% CI –0.93 to 0.63}. Serious non-mesh adverse effects rates were similar between the groups in year 1 [standard 7.2% vs. mesh 7.8%, risk ratio (RR) 1.08, 95% CI 0.68 to 1.72; standard 6.3% vs. graft 9.8%, RR 1.57, 95% CI 0.95 to 2.59]. There were no statistically significant differences between groups in any other outcome measure. The cumulative mesh complication rates over 2 years were 2 of 430 (0.5%) for standard repair (trial 1), 46 of 435 (10.6%) for mesh inlay and 2 of 368 (0.5%) for biological graft. The CC findings were comparable. Incremental costs were £363 (95% CI –£32 to £758) and £565 (95% CI £180 to £950) for mesh and graft vs. standard, respectively. Incremental QALYs were 0.071 (95% CI –0.004 to 0.145) and 0.039 (95% CI –0.041 to 0.120) for mesh and graft vs. standard, respectively. A Markov decision model extrapolating trial results over 5 years showed standard repair had the highest probability of cost-effectiveness, but results were surrounded by considerable uncertainty.Secondary trials: there were no statistically significant differences between the randomised groups in any outcome measure, but the sample size was too small to be conclusive. The cumulative mesh complication rates over 2 years were 7 of 52 (13.5%) for mesh inlay and 4 of 46 (8.7%) for mesh kit, with no mesh exposures for standard repair.ConclusionsIn women who were having primary repairs, there was evidence of no benefit from the use of mesh inlay or biological graft compared with standard repair in terms of efficacy, QoL or adverse effects (other than mesh complications) in the short term. The Secondary trials were too small to provide conclusive results.LimitationsWomen in the Primary trials included some with a previous repair in another compartment. Follow-up is vital to identify any long-term potential benefits and serious adverse effects.Future workLong-term follow-up to at least 6 years after surgery is ongoing to identify recurrence rates, need for further prolapse surgery, adverse effects and cost-effectiveness.TriaI registrationCurrent Controlled Trials ISRCTN60695184.FundingThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 20, No. 95. See the NIHR Journals Library website for further project information.

scholarly journals Adalimumab, etanercept and ustekinumab for treating plaque psoriasis in children and young people: systematic review and economic evaluation

2017 ◽  
Vol 21 (64) ◽  
pp. 1-244 ◽  
Author(s):  
Ana Duarte ◽  
Teumzghi Mebrahtu ◽  
Pedro Saramago Goncalves ◽  
Melissa Harden ◽  
Ruth Murphy ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Young People ◽  
Clinical Effectiveness ◽  
Children And Young People ◽  
Biological Treatments ◽  
Randomised Controlled ◽  
The Cost

Background Psoriasis is a chronic inflammatory disease that predominantly affects the skin. Adalimumab (HUMIRA®, AbbVie, Maidenhead, UK), etanercept (Enbrel®, Pfizer, New York, NY, USA) and ustekinumab (STELARA®, Janssen Biotech, Inc., Titusville, NJ, USA) are the three biological treatments currently licensed for psoriasis in children. Objective To determine the clinical effectiveness and cost-effectiveness of adalimumab, etanercept and ustekinumab within their respective licensed indications for the treatment of plaque psoriasis in children and young people. Data sources Searches of the literature and regulatory sources, contact with European psoriasis registries, company submissions and clinical study reports from manufacturers, and previous National Institute for Health and Care Excellence (NICE) technology appraisal documentation. Review methods Included studies were summarised and subjected to detailed critical appraisal. A network meta-analysis incorporating adult data was developed to connect the effectiveness data in children and young people and populate a de novo decision-analytic model. The model estimated the cost-effectiveness of adalimumab, etanercept and ustekinumab compared with each other and with either methotrexate or best supportive care (BSC), depending on the position of the intervention in the management pathway. Results Of the 2386 non-duplicate records identified, nine studies (one randomised controlled trial for each drug plus six observational studies) were included in the review of clinical effectiveness and safety. Etanercept and ustekinumab resulted in significantly greater improvements in psoriasis symptoms than placebo at 12 weeks’ follow-up. The magnitude and persistence of the effects beyond 12 weeks is less certain. Adalimumab resulted in significantly greater improvements in psoriasis symptoms than methotrexate for some but not all measures at 16 weeks. Quality-of-life benefits were inconsistent across different measures. There was limited evidence of excess short-term adverse events; however, the possibility of rare events cannot be excluded. The majority of the incremental cost-effectiveness ratios for the use of biologics in children and young people exceeded NICE’s usual threshold for cost-effectiveness and were reduced significantly only when combined assumptions that align with those made in the management of psoriasis in adults were adopted. Limitations The clinical evidence base for short- and long-term outcomes was limited in terms of total participant numbers, length of follow-up and the absence of young children. Conclusions The paucity of clinical and economic evidence to inform the cost-effectiveness of biological treatments in children and young people imposed a number of strong assumptions and uncertainties. Health-related quality-of-life (HRQoL) gains associated with treatment and the number of hospitalisations in children and young people are areas of considerable uncertainty. The findings suggest that biological treatments may not be cost-effective for the management of psoriasis in children and young people at a willingness-to-pay threshold of £30,000 per quality-adjusted life-year, unless a number of strong assumptions about HRQoL and the costs of BSC are combined. Registry data on biological treatments would help determine safety, patterns of treatment switching, impact on comorbidities and long-term withdrawal rates. Further research is also needed into the resource use and costs associated with BSC. Adequately powered randomised controlled trials (including comparisons against placebo) could substantially reduce the uncertainty surrounding the effectiveness of biological treatments in biologic-experienced populations of children and young people, particularly in younger children. Such trials should establish the impact of biological therapies on HRQoL in this population, ideally by collecting direct estimates of EuroQol-5 Dimensions for Youth (EQ-5D-Y) utilities. Study registration This study is registered as PROSPERO CRD42016039494. Funding The National Institute for Health Research Health Technology Assessment programme.

scholarly journals Long-term outcomes of two-stage, immediate and delayed breast reconstruction with polyurethane-covered versus textured implants: protocol of a prospective, multicentre randomised controlled trial (TIPI trial)

BMJ Open ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. e044219
Author(s):  
J X Harmeling ◽  
Kevin Peter Cinca ◽  
Eleni-Rosalina Andrinopoulou ◽  
Eveline M L Corten ◽  
M A Mureau
Keyword(s):  
Randomised Controlled Trial ◽  
Breast Reconstruction ◽  
Controlled Trial ◽  
Capsular Contracture ◽  
Tissue Expander ◽  
Complication Rates ◽  
Two Stage ◽  
Randomised Controlled

IntroductionTwo-stage implant-based breast reconstruction is the most commonly performed postmastectomy reconstructive technique. During the first stage, a tissue expander creates a sufficiently large pocket for the definite breast implant placed in the second stage. Capsular contracture is a common long-term complication associated with implant-based breast reconstruction, causing functional complaints and often requiring reoperation. The exact aetiology is still unknown, but a relationship between the outer surface of the implant and the probability of developing capsular contracture has been suggested. The purpose of this study is to determine whether polyurethane-covered implants result in a different capsular contracture rate than textured implants.Methods and analysisThe Textured Implants versus Polyurethane-covered Implants (TIPI) trial is a multicentre randomised controlled trial with a 1:1 allocation rate and a follow-up of 10 years. A total of 321 breasts of female adults undergoing a two-stage breast reconstruction will be enrolled. The primary outcome is capsular contracture at 10-year follow-up which is graded with the modified Baker classification. It is analysed with survival analysis using a frailty model for clustered interval-censored data, with both an intention-to-treat and per-protocol approach. Secondary outcomes are other complication rates, surgical revision rate, patient satisfaction and quality of life and user-friendliness. Outcomes are measured 2 weeks, 6 months, 1, 2, 3, 5 and 10 years postoperatively. Interim analysis is performed when 1-year, 3-year and 5-year follow-up is completed.Ethics and disseminationThe trial has been reviewed and approved by the Medical Research Ethics Committee of the Erasmus MC, University Medical Centre Rotterdam (MEC-2018-126) and locally by each participating centre. Written informed consent will be obtained from each study participant. The results will be disseminated by publication in peer-reviewed journals.Trial registrationNTR7265.

scholarly journals Cost-effectiveness of an app-based treatment for urinary incontinence in comparison to care as usual in general practice: A pragmatic randomised controlled trial over 12 months

2021 ◽  
Author(s):  
Anne Loohuis ◽  
Henk van der Worp ◽  
Nienke Wessels ◽  
Janny Dekker ◽  
Marijke Slieker-ten Hove ◽  
...  
Keyword(s):  
Primary Care ◽  
Urinary Incontinence ◽  
Cost Effectiveness ◽  
Mobile Apps ◽  
Controlled Trial ◽  
Intention To Treat ◽  
Life Years ◽  
Randomised Controlled

Objective: Long-term cost-effectiveness of app-based treatment for female stress, urgency, or mixed urinary incontinence (UI) compared to care-as-usual in primary care. Design: A pragmatic, randomised controlled, superiority trial. Setting: Primary care in the Netherlands from 2015 to 2018, follow-up at 12 months. Population: Women with ≥2 UI-episodes per week, access to mobile apps, wanting treatment. 262 women randomised equally to app or care-as-usual; 89 (68%) and 83 (63%) attended follow-up. Methods: The standalone app included conservative management for UI with motivation aids (e.g., reminders). Care-as-usual delivered according to the Dutch GP guideline for UI. Main outcome measures: Effectiveness assessed by the change in symptom severity score (ICIQ-UI-SF) and the change in quality of life (ICIQ-LUTS-QoL, EQ-5D-5L) on superiority with linear regression on an intention-to-treat basis. Cost-effectiveness and -utility from a societal perspective, based on Incontinence Impact Adjusted Life Years (IIALYs) and Quality Adjusted Life years (QALYs). Results: Clinically relevant improvement of UI severity for both app (-2.17 ± 2.81) and care-as-usual (-3.43 ± 3.6), with a non-significant mean difference of 0.903 (-0.66 to 1.871). Costs were lower for app-based treatment with \euro-161 (95%CI: -180 to -151) per year. Cost-effectiveness showed small mean differences in effect for IIALY (0.04) and QALY (-0.03) and thus larger ICER (-3,696) and ICUR (\euro6,379). Conclusion: App-based treatment is a viable alternative to care-as-usual for UI in primary care in terms of long-term cost-effectiveness. Funding: Dutch Organisation for Health Research and Development (ZonMw: 837001508), sub-funding P.W. Boer Foundation Dutch Trial Register identifier: Trial NL4948 (www.trialregister.nl/trial/4948).

scholarly journals Long-term antipsychotic treatment in schizophrenia: systematic review and network meta-analysis of randomised controlled trials

BJPsych Open ◽  
2016 ◽  
Vol 2 (1) ◽  
pp. 59-66 ◽  
Author(s):  
Ying Jiao Zhao ◽  
Liang Lin ◽  
Monica Teng ◽  
Ai Leng Khoo ◽  
Lay Beng Soh ◽  
...  
Keyword(s):  
Weight Gain ◽  
Adverse Effects ◽  
Randomised Controlled Trials ◽  
Antipsychotic Drugs ◽  
Meta Analysis ◽  
Antipsychotic Treatment ◽  
Controlled Trials ◽  
Fluphenazine Decanoate ◽  
Randomised Controlled

BackgroundFor treatment of patients diagnosed with schizophrenia, comparative long-term effectiveness of antipsychotic drugs to reduce relapses when minimising adverse effects is of clinical interest, hence prompting this review.AimsTo evaluate the comparative long-term effectiveness of antipsychotic drugs.MethodWe systematically searched electronic databases for reports of randomised controlled trials (RCTs) of antipsychotic monotherapy aimed at reducing relapse risks in schizophrenia. We conducted network meta-analysis of 18 antipsychotics and placebo.ResultsStudies of 10 177 patients in 56 reports were included; treatment duration averaged 48 weeks (range 4–156). Olanzapine was significantly more effective than chlorpromazine (odds ratio (OR) 0.35, 95% CI 0.14–0.88) or haloperidol (OR=0.50, 95% CI 0.30–0.82); and fluphenazine decanoate was more effective than chlorpromazine (OR=0.31, 95% CI 0.11–0.88) in relapse reduction. Fluphenazine decanoate, haloperidol, haloperidol decanoate and trifluoperazine produced more extrapyramidal adverse effects than olanzapine or quetiapine; and olanzapine was associated with more weight gain than other agents.ConclusionsExcept for apparent superiority of olanzapine and fluphenazine decanoate over chlorpromazine, most agents showed intermediate efficacy for relapse prevention and differences among them were minor. Typical antipsychotics yielded adverse neurological effects, and olanzapine was associated with weight gain. The findings may contribute to evidence-based treatment selection for patients with chronic psychotic disorders.

Effectiveness of exercise-based interventions in reducing depressive symptoms in people without clinical depression: systematic review and meta-analysis of randomised controlled trials

2021 ◽  
pp. 1-10
Author(s):  
Juan Ángel Bellón ◽  
Sonia Conejo-Cerón ◽  
Almudena Sánchez-Calderón ◽  
Beatriz Rodríguez-Martín ◽  
Darío Bellón ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Sample Size ◽  
Randomised Controlled Trials ◽  
Clinical Depression ◽  
Sensitivity Analyses ◽  
Controlled Trials ◽  
Long Term Follow Up ◽  
Randomised Controlled

Background In most trials and systematic reviews that evaluate exercise-based interventions in reducing depressive symptoms, it is difficult to separate treatment from prevention. Aims To evaluate the effectiveness of exercise-based interventions in reducing depressive symptoms in people without clinical depression. Method We searched PubMed, PsycINFO, Embase, WOS, SPORTDiscus, CENTRAL, OpenGrey and other sources up to 25 May 2020. We selected randomised controlled trials (RCTs) that compared exclusively exercise-based interventions with control groups, enrolling participants without clinical depression, as measured using validated instruments, and whose outcome was reduction of depressive symptoms and/or incidence of new cases of people with depression. Pooled standardised mean differences (SMDs) were calculated using random-effect models (registration at PROSPERO: CRD42017055726). Results A total of 14 RCTs (18 comparisons) evaluated 1737 adults without clinical depression from eight countries and four continents. The pooled SMD was −0.34 (95% CI −0.51 to −0.17; P < 0.001) and sensitivity analyses confirmed the robustness of this result. We found no statistical evidence of publication bias and heterogeneity was moderate (I2 = 54%; 95% CI 22–73%). Only two RCTs had an overall low risk of bias and three had long-term follow-up. Multivariate meta-regression found that a larger sample size, country (Asia) and selective prevention (i.e. people exposed to risk factors for depression) were associated with lower effectiveness, although only sample size remained significant when adjustment for multiple tests was considered. According to the Grading of Recommendations Assessment, Development and Evaluation tool, the quality of evidence was low. Conclusions Exercise-based interventions have a small effect on the reduction of depressive symptoms in people without clinical depression. It could be an alternative to or complement psychological programmes, although further higher-quality trials with larger samples and long-term follow-up are needed.

scholarly journals Child outcomes after induction of labour or expectant management in women with preterm prelabour rupture of membranes between 34 and 37 weeks of gestation: study protocol of the PPROMEXIL Follow-up trial. A long-term follow-up study of the randomised controlled trials PPROMEXIL and PPROMEXIL-2

BMJ Open ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. e046046
Author(s):  
Annemijn A de Ruigh ◽  
Noor E Simons ◽  
Janneke Van ‘t Hooft ◽  
Aleid G van Wassenaer-Leemhuis ◽  
Cornelieke S H Aarnoudse-Moens ◽  
...  
Keyword(s):  
Randomised Controlled Trials ◽  
Expectant Management ◽  
Induction Of Labour ◽  
Late Preterm ◽  
Controlled Trials ◽  
Link Type ◽  
Long Term Follow Up ◽  
Randomised Controlled

IntroductionLate preterm prelabour rupture of membranes (PROM between 34+0 and 36+6 weeks gestational age) is an important clinical dilemma. Previously, two large Dutch randomised controlled trials (RCTs) compared induction of labour (IoL) to expectant management (EM). Both trials showed that early delivery does not reduce the risk of neonatal sepsis as compared with EM, although prematurity-related risks might increase. An extensive, structured long-term follow-up of these children has never been performed.Methods and analysisThe PPROMEXIL Follow-up trial (NL6623 (NTR6953)) aims to assess long-term childhood outcomes of the PPROMEXIL (ISRCTN29313500) and PPROMEXIL-2 trial (ISRCTN05689407), two multicentre RCTs using the same protocol, conducted between 2007 and 2010 evaluating IoL versus EM in women with late preterm PROM. The PPROMEXIL Follow-up will analyse children of mothers with a singleton pregnancy (PPROMEXIL trial n=520, PPROMEXIL-2 trial n=191, total IoL n=359; total EM n=352). At 10–12 years of age all surviving children will be invited for a neurodevelopmental assessment using the Wechsler Intelligence Scale for Children-V, Color-Word Interference Test and the Movement Assessment Battery for Children-2. Parents will be asked to fill out questionnaires assessing behaviour, motor function, sensory processing, respiratory problems, general health and need for healthcare services. Teachers will fill out the Teacher Report Form and answer questions regarding school attainment. For all tests means with SDs will be compared, as well as predefined cut-off scores for abnormal outcome. Sensitivity analyses consisting of different imputation techniques will be used to deal with lost to follow-up.Ethics and disseminationThe study has been granted approval by the Medical Centre Amsterdam (MEC) of the AmsterdamUMC (MEC2016_217). Results will be disseminated through peer-reviewed journals and summaries shared with stakeholders. This protocol is published before analysis of the results.Trial registration numberNL6623 (NTR6953).

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