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1.
Res Synth Methods ; 2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32367691

RESUMO

Traditional visualization in meta-analysis uses forest plots to illustrate the combined treatment effect, along with the respective results from primary trials. While the purpose of visualization is clear in the pairwise setting, additional treatments broaden the focus and extend the results to be illustrated in network meta-analysis. The complexity increases further in situations where all potential contrasts in the network are compared to a predefined fixed value of interest, such as the 95% coverage evaluated against the nominal value of 95% in simulation studies. We propose utilizing radar graphs to illustrate results from network meta-analysis in cases where the interest lies in the comparison of estimated results (after fitting a network meta-analysis in a specific data set) or a performance measure (simulation study) to a pre-defined fixed reference value. Accounting for the complex high-dimensional data structure, the general picture of the full network is captured at once without increasing the space needed for visualization. Especially in large simulation studies, where multiple scenarios need to be visually combined to gain an overview on different scenarios, this type of illustration facilitates the discussion of results. Further properties, such as the expected variation due to the Monte-Carlo error or the differentiation between directly and indirectly estimated treatment contrasts in simulation studies, as well as the indication of well-connected and sparsely connected treatments in an applied network meta-analysis, can additionally be included in the visualization. While we used the radar-graph mainly for a simulation study, other applications are suitable whenever relative contributions of treatment (contrasts) are of interest.

2.
ESC Heart Fail ; 2020 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-32285648

RESUMO

AIMS: Patients with non-ischaemic dilated cardiomyopathy (DCM) are at increased risk of sudden cardiac death. Identification of patients that may benefit from implantable cardioverter-defibrillator implantation remains challenging. In this study, we aimed to determine predictors of sustained ventricular arrhythmias in patients with DCM. METHODS AND RESULTS: We searched MEDLINE/Embase for studies describing predictors of sustained ventricular arrhythmias in patients with DCM. Quality and bias were assessed using the Quality in Prognostic Studies tool, articles with high risk of bias in ≥2 areas were excluded. Unadjusted hazard ratios (HRs) of uniformly defined predictors were pooled, while all other predictors were evaluated in a systematic review. We included 55 studies (11 451 patients and 3.7 ± 2.3 years follow-up). Crude annual event rate was 4.5%. Younger age [HR 0.82; 95% CI (0.74-1.00)], hypertension [HR 1.95; 95% CI (1.26-3.00)], prior sustained ventricular arrhythmia [HR 4.15; 95% CI (1.32-13.02)], left ventricular ejection fraction on ultrasound [HR 1.45; 95% CI (1.19-1.78)], left ventricular dilatation (HR 1.10), and presence of late gadolinium enhancement [HR 5.55; 95% CI (4.02-7.67)] were associated with arrhythmic outcome in pooled analyses. Prior non-sustained ventricular arrhythmia and several genotypes [mutations in Phospholamban (PLN), Lamin A/C (LMNA), and Filamin-C (FLNC)] were associated with arrhythmic outcome in non-pooled analyses. Quality of evidence was moderate, and heterogeneity among studies was moderate to high. CONCLUSIONS: In patients with DCM, the annual event rate of sustained ventricular arrhythmias is approximately 4.5%. This risk is considerably higher in younger patients with hypertension, prior (non-)sustained ventricular arrhythmia, decreased left ventricular ejection fraction, left ventricular dilatation, late gadolinium enhancement, and genetic mutations (PLN, LMNA, and FLNC). These results may help determine appropriate candidates for implantable cardioverter-defibrillator implantation.

3.
Artigo em Alemão | MEDLINE | ID: mdl-32175805

RESUMO

Empirically based developmental and behavioral intervention programs targeting the core symptoms and language development in toddlers and preschool children with autism spectrum disorder Abstract. This systematic review summarizes findings of articles included in the German AWMF-S3 clinical guideline on early intervention in autism spectrum disorders (ASD). We present the current state-of the art of evidence-based interventions for toddlers and preschool-aged children with ASD, specifically targeting the core symptoms and language development. We included studies on manualized developmental and behavioral interventions for children with ASD aged <7 years according to DSM-III(R), DSM-IV(TR), DSM-5, and ICD-10. The publication dates ranged from 1 January 2011 to 31 August 2018 or as included in the NICE-children guidelines. Studies were included by an iterative hierarchy: systematic review > randomized-controlled trial > clinically controlled trial. Outcome measures were core ASD symptoms and precursor abilities, or language abilities. The interventions were collated by (1) frequency and (2) approach. The studies focused on low-intensive interventions targeting parental synchrony, the child's initiations, reciprocity, joint attention, play and imitation skills as well as comprehensive interventions. Improvement of core ASD symptoms regarding social communication was observed for low-intensive training of parental synchrony and child's reciprocity as well as for low-intensive comprehensive developmental interventions implementing natural-learning paradigms. High-frequency discrete trial interventions did not improve social communication. Language abilities improved by comprehensive interventions. In conclusion, intervention recommendations are summarized.


Assuntos
Transtorno do Espectro Autista/psicologia , Transtorno do Espectro Autista/terapia , Terapia Comportamental , Prática Clínica Baseada em Evidências , Desenvolvimento da Linguagem , Prevenção Secundária , Criança , Pré-Escolar , Humanos , Pais/psicologia , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
Eur J Prev Cardiol ; : 2047487320905719, 2020 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-32089005

RESUMO

BACKGROUND: Despite numerous studies and meta-analyses the prognostic effect of cardiac rehabilitation is still under debate. This update of the Cardiac Rehabilitation Outcome Study (CROS II) provides a contemporary and practice focused approach including only cardiac rehabilitation interventions based on published standards and core components to evaluate cardiac rehabilitation delivery and effectiveness in improving patient prognosis. DESIGN: A systematic review and meta-analysis. METHODS: Randomised controlled trials and retrospective and prospective controlled cohort studies evaluating patients after acute coronary syndrome, coronary artery bypass grafting or mixed populations with coronary artery disease published until September 2018 were included. RESULTS: Based on CROS inclusion criteria out of 7096 abstracts six additional studies including 8671 patients were identified (two randomised controlled trials, two retrospective controlled cohort studies, two prospective controlled cohort studies). In total, 31 studies including 228,337 patients were available for this meta-analysis (three randomised controlled trials, nine prospective controlled cohort studies, 19 retrospective controlled cohort studies; 50,653 patients after acute coronary syndrome 14,583, after coronary artery bypass grafting 163,101, mixed coronary artery disease populations; follow-up periods ranging from 9 months to 14 years). Heterogeneity in design, cardiac rehabilitation delivery, biometrical assessment and potential confounders was considerable. Controlled cohort studies showed a significantly reduced total mortality (primary endpoint) after cardiac rehabilitation participation in patients after acute coronary syndrome (prospective controlled cohort studies: hazard ratio (HR) 0.37, 95% confidence interval (CI) 0.20-0.69; retrospective controlled cohort studies HR 0.64, 95% CI 0.53-0.76; prospective controlled cohort studies odds ratio 0.20, 95% CI 0.08-0.48), but the single randomised controlled trial fulfilling the CROS inclusion criteria showed neutral results. Cardiac rehabilitation participation was also associated with reduced total mortality in patients after coronary artery bypass grafting (retrospective controlled cohort studies HR 0.62, 95% CI 0.54-0.70, one single randomised controlled trial without fatal events), and in mixed coronary artery disease populations (retrospective controlled cohort studies HR 0.52, 95% CI 0.36-0.77; two out of 10 controlled cohort studies with neutral results). CONCLUSION: CROS II confirms the effectiveness of cardiac rehabilitation participation after acute coronary syndrome and after coronary artery bypass grafting in actual clinical practice by reducing total mortality under the conditions of current evidence-based coronary artery disease treatment. The data of CROS II, however, underscore the urgent need to define internationally accepted minimal standards for cardiac rehabilitation delivery as well as for scientific evaluation.

5.
Trials ; 21(1): 217, 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32093772

RESUMO

BACKGROUND: Naturalistic developmental behavioural interventions (NDBI) have been shown to improve autism-specific symptoms in young children with Autism Spectrum Disorder (ASD). NDBI approaches, such as the ASD-specific Frankfurt Early Intervention Programme for ASD (A-FFIP), are based on ASD-specific developmental and learning aspects. A-FFIP is a low-intensity intervention which can easily be implemented in the local health care/social welfare system. The aim of the present study is to establish 1-year efficacy of the manualised early intervention programme A-FFIP in toddlers and preschool children with ASD. It is hypothesised that A-FFIP will result in improved ASD-specific symptoms compared to early intervention as usual (EIAU). Child- and family-specific secondary outcomes, as well as moderators and mediators of outcome, will be explored. METHODS/DESIGN: A prospective, multi-centre, parallel-group, randomised controlled, phase-III trial comparing A-FFIP versus EIAU. A total of 134 children (A-FFIP: 67, EIAU: 67) aged 24-66 months at baseline assessment meeting the criteria for ASD (DSM-5) will be included. The primary outcome is the absolute change of the total score of the Brief Observation of Social Communication Change (BOSCC-AT) between baseline (T2) and 1-year follow-up (T6). The treatment effect will be tested, adjusted for relevant covariates applying a mixed model for repeated measures. Secondary outcomes are BOSCC social communication and repetitive-behaviour scores, single ASD symptoms, language, cognition, psychopathology, parental well-being and family quality of life. Predictors, moderators and mediating mechanisms will be explored. DISCUSSION: If efficacy of the manualised A-FFIP early intervention is established, the current study has the potential to change clinical practice strongly towards the implementation of a low-intensity, evidence-based, natural early intervention in ASD. Early intervention in ASD requires specialist training, which subsequently needs to be developed or included into current training curricula. TRIAL REGISTRATION: German Registry for Clinical Trials (Deutscher Register Klinischer Studien, DRKS); ID: 00016330. Retrospectively registered on 4 January 2019. URL: https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00016330.

6.
Res Synth Methods ; 11(3): 363-378, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31955519

RESUMO

The performance of statistical methods is often evaluated by means of simulation studies. In case of network meta-analysis of binary data, however, simulations are not currently available for many practically relevant settings. We perform a simulation study for sparse networks of trials under between-trial heterogeneity and including multi-arm trials. Results of the evaluation of two popular frequentist methods and a Bayesian approach using two different prior specifications are presented. Methods are evaluated using coverage, width of intervals, bias, and root mean squared error (RMSE). In addition, deviations from the theoretical surface under the cumulative rankings (SUCRAs) or P-scores of the treatments are evaluated. Under low heterogeneity and when a large number of trials informs the contrasts, all methods perform well with respect to the evaluated performance measures. Coverage is observed to be generally higher for the Bayesian than the frequentist methods. The width of credible intervals is larger than those of confidence intervals and is increasing when using a flatter prior for between-trial heterogeneity. Bias was generally small, but increased with heterogeneity, especially in netmeta. In some scenarios, the direction of bias differed between frequentist and Bayesian methods. The RMSE was comparable between methods but larger in indirectly than in directly estimated treatment effects. The deviation of the SUCRAs or P-scores from their theoretical values was mostly comparable over the methods but differed depending on the heterogeneity and the geometry of the investigated network. Multivariate meta-regression or Bayesian estimation using a half-normal prior scaled to 0.5 seems to be promising with respect to the evaluated performance measures in network meta-analysis of sparse networks.

7.
Cochrane Database Syst Rev ; 1: CD011935, 2020 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-31912907

RESUMO

BACKGROUND: People with urothelial carcinoma of the bladder are at risk for recurrence and progression following transurethral resection of a bladder tumour (TURBT). Mitomycin C (MMC) and Bacillus Calmette-Guérin (BCG) are commonly used, competing forms of intravesical therapy for intermediate- or high-risk non-muscle invasive (Ta and T1) urothelial bladder cancer but their relative merits are somewhat uncertain. OBJECTIVES: To assess the effects of BCG intravesical therapy compared to MMC intravesical therapy for treating intermediate- and high-risk Ta and T1 bladder cancer in adults. SEARCH METHODS: We performed a systematic literature search in multiple databases (CENTRAL, MEDLINE, Embase, Web of Science, Scopus, LILACS), as well as in two clinical trial registries. We searched reference lists of relevant publications and abstract proceedings. We applied no language restrictions. The latest search was conducted in September 2019. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared intravesical BCG with intravesical MMC therapy for non-muscle invasive urothelial bladder cancer. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the literature, extracted data, assessed risk of bias and rated the quality of evidence according to GRADE per outcome. In the meta-analyses, we used the random-effects model. MAIN RESULTS: We identified 12 RCTs comparing BCG versus MMC in participants with intermediate- and high-risk non-muscle invasive bladder tumours (published from 1995 to 2013). In total, 2932 participants were randomised. Time to death from any cause: BCG may make little or no difference on time to death from any cause compared to MMC (hazard ratio (HR) 0.97, 95% confidence interval (CI) 0.79 to 1.20; participants = 1132, studies = 5; 567 participants in the BCG arm and 565 in the MMC arm; low-certainty evidence). This corresponds to 6 fewer deaths (40 fewer to 36 more) per 1000 participants treated with BCG at five years. We downgraded the certainty of the evidence two levels due to study limitations and imprecision. Serious adverse effects: 12/577 participants treated with BCG experienced serious non-fatal adverse effects compared to 4/447 participants in the MMC group. The pooled risk ratio (RR) is 2.31 (95% CI 0.82 to 6.52; participants = 1024, studies = 5; low-certainty evidence). Therefore, BCG may increase the risk for serious adverse effects compared to MMC. This corresponds to nine more serious adverse effects (one fewer to 37 more) with BCG. We downgraded the certainty of the evidence two levels due to study limitations and imprecision. Time to recurrence: BCG may reduce the time to recurrence compared to MMC (HR 0.88, 95% CI 0.71 to 1.09; participants = 2616, studies = 11, 1273 participants in the BCG arm and 1343 in the MMC arm; low-certainty evidence). This corresponds to 41 fewer recurrences (104 fewer to 29 more) with BCG at five years. We downgraded the certainty of the evidence two levels due to study limitations, imprecision and inconsistency. Time to progression: BCG may make little or no difference on time to progression compared to MMC (HR 0.96, 95% CI 0.73 to 1.26; participants = 1622, studies = 6; 804 participants in the BCG arm and 818 in the MMC arm; low-certainty evidence). This corresponds to four fewer progressions (29 fewer to 27 more) with BCG at five years. We downgraded the certainty of the evidence two levels due to study limitations and imprecision. Quality of life: we found very limited data for this outcomes and were unable to estimate an effect size. AUTHORS' CONCLUSIONS: Based on our findings, BCG may reduce the risk of recurrence over time although the Confidence Intervals include the possibility of no difference. It may have no effect on either the risk of progression or risk of death from any cause over time. BCG may cause more serious adverse events although the Confidence Intervals once again include the possibility of no difference. We were unable to determine the impact on quality of life. The certainty of the evidence was consistently low, due to concerns that include possible selection bias, performance bias, given the lack of blinding in these studies, and imprecision.


Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Mitomicina/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Administração Intravesical , Antibióticos Antineoplásicos/administração & dosagem , Vacina BCG , Humanos , Mitomicina/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
8.
Artigo em Inglês | MEDLINE | ID: mdl-30971173

RESUMO

Abstracts: Objective: In current international research, early intervention in children with autism-spectrum disorder (ASD) focuses on naturalistic developmental behavioral interventions (NDBI). The manualized Frankfurt Early Intervention Program for preschool-aged children with ASD (A-FFIP) implements NDBI principles within a low-intensity approach of 2 h intervention/week. The present case-control study established effect sizes of change in autistic symptoms, comorbid behavioral problems as well as IQ after one year. Methodology: An intervention group (N = 20; age: 3.4-7.9 years) and a treatment-as-usual control group (N = 20; age: 3.2-7.3 years) of children with ASD were matched for developmental and chronological age. The outcome measures used were the ADOS severity score, the Child Behavior Checklist, and cognitive development. Results: After one year, the A-FFIP group showed a trend towards greater improvement in autistic symptoms (η2 = .087 [95 %-CI: .000-.159]) and significantly greater improvements in cognitive development (η2 = .206 [CI: .012-.252]) and global psychopathology (η2 = .144 [CI: .001-.205]) compared to the control group. Conclusion: The efficacy of A-FFIP should be established in a larger, sufficiently powered, randomized controlled study.


Assuntos
Transtorno do Espectro Autista/psicologia , Transtorno do Espectro Autista/terapia , Terapia Comportamental , Transtorno Autístico/psicologia , Transtorno Autístico/terapia , Estudos de Casos e Controles , Criança , Pré-Escolar , Humanos , Resultado do Tratamento
9.
Biom J ; 62(3): 777-789, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31544262

RESUMO

Individualized therapies for patients with biomarkers are moving more and more into the focus of research interest when developing new treatments. Hereby, the term individualized (or targeted) therapy denotes a treatment specifically developed for biomarker-positive patients. A network meta-analysis model for a binary endpoint combining the evidence for a targeted therapy from individual patient data with the evidence for a non-targeted therapy from aggregate data is presented and investigated. The biomarker status of the patients is either available at patient-level in individual patient data or at study-level in aggregate data. Both types of biomarker information have to be included. The evidence synthesis model follows a Bayesian approach and applies a meta-regression to the studies with aggregate data. In a simulation study, we address three treatment arms, one of them investigating a targeted therapy. The bias and the root-mean-square error of the treatment effect estimate for the subgroup of biomarker-positive patients based on studies with aggregate data are investigated. Thereby, the meta-regression approach is compared to approaches applying alternative solutions. The regression approach has a surprisingly small bias even in the presence of few studies. By contrast, the root-mean-square error is relatively greater. An illustrative example is provided demonstrating implementation of the presented network meta-analysis model in a clinical setting.

10.
Heart Fail Rev ; 25(2): 161-171, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31364027

RESUMO

This study aims to assess the comparative benefit and risk profile of treatment with mineralocorticoid receptor antagonists (MRAs) with regard to all-cause mortality (primary endpoint), cardiovascular mortality, or heart failure (HF)-related hospitalization (secondary endpoints) and the safety endpoints hyperkalemia, acute renal failure, and gynecomastia in patients with chronic HF. We conducted a systematic review and network meta-analysis following PRISMA-P and PRISMA-NMA guidelines. From 16 different sources, 14 randomized controlled trials totaling 12,213 patients testing an active treatment of either spironolactone, eplerenone, or canrenone/potassium-canreonate in adults with symptomatic HF due to systolic dysfunction reporting any of the above endpoints were retained. Efficacy in comparison to placebo/standard medical care with respect to all-cause mortality was confirmed for spironolactone and eplerenone while no conclusion could be drawn for canrenone (HR 0.69 (0.62; 0.77), 0.82 (0.75; 0.91), and 0.50 (0.17; 1.45), respectively). Indirect comparisons hint a potential (non-significant) preference of spironolactone over eplerenone (HR 0.84 (0.68; 1.03)). The overall risk of bias was low to intermediate. Results for secondary endpoints as well as sensitivity analyses essentially mirrored these findings. The beta-blocker adjusted meta-analysis for the primary endpoint showed the same tendency as the unadjusted one (HR 0.39 (0.07; 2.03)). Results need to be interpreted with caution, though, as the resultant mix of patient- and study-level covariates produced unstable statistical modeling. We found no significant and systematic superiority of either MRA regarding efficacy toward all endpoints considered in both direct and indirect comparisons.

11.
Eur J Cancer ; 123: 101-111, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31678767

RESUMO

INTRODUCTION: Disease-free survival (DFS) is increasingly being used as surrogate end-point for overall survival (OS) in cancer trials. So far, there has been no validation of the surrogacy of DFS for OS for neoadjuvant treatment of gastroesophageal adenocarcinoma. METHODS: The study uses individual patient data (IPD) from eight randomised controlled trials (RCTs) (n = 1126 patients) comparing neoadjuvant therapy followed by surgery with surgery alone for gastroesophageal adenocarcinoma. Correlation between OS time and DFS time was calculated to evaluate individual-level surrogacy. For each trial, survival curves using the Kaplan-Meier method were plotted and hazard ratios (HRs) on the treatment effects were calculated for OS and DFS separately. Those HRs were pooled in a random-effects meta-analysis. Observed HRs were compared with predicted HRs for OS using results from an error-in-variables linear regression model accounting for the uncertainty about the estimated effect. The strength of the association was quantified by the coefficient of determination to assess trial-level surrogacy. The surrogate threshold effect was calculated to determine the minimum treatment effect on DFS necessary to predict a non-zero treatment effect on OS. RESULTS: A strong correlation between OS time and DFS time was observed, indicating a high individual-level surrogacy. For all RCTs, estimated HRs for OS and DFS were highly similar. In the meta-analysis, the overall HR for OS was virtually identical to that for DFS. The estimated coefficient of determination r2 for the association between HRs for OS and DFS was 0.912 (95% confidence interval: 0.75-1.0), indicating a very good fit of the regression model and thus a strong trial-level surrogacy between OS and DFS. The surrogate threshold effect based on the regression analysis was 0.79. DISCUSSION: Based on strong correlations between DFS and OS, as well as a strong correlation of the treatment effects of the two end-points in the error-in-variable regression, DFS seems an appropriate surrogate marker for OS in randomised trials of neoadjuvant chemotherapy or chemoradiotherapy for gastroesophageal adenocarcinoma.

12.
BMJ Open ; 9(9): e032353, 2019 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-31575583

RESUMO

INTRODUCTION: Pancreatic surgery is a large and complex field of research. Several evidence gaps exist for specific diseases or surgical procedures. An overview on existing knowledge is needed to plan and prioritise future research. The aim of this project is to create a systematic and living evidence map of pancreatic surgery. METHODS AND ANALYSIS: A systematic literature search in MEDLINE (via PubMed), Web of Science and Cochrane Central Register of Controlled Trials will be performed searching for all randomised controlled trials (RCT) and systematic reviews (SR) on pancreatic surgery. RCT and SR will be grouped in research topics. Baseline and outcome data from RCT will be extracted, presented and effect sizes meta-analysed. Data from SR will be used to identify evidence gaps. A freely accessible web-based evidence map in the format of a mind map will be created. The evidence map and meta-analyses will be updated periodically. DISSEMINATION: After completion of the project, a permanently updated evidence map of pancreatic surgery will be available to patients, physicians, researchers and funding bodies via www.evidencemap.surgery. Its use will allow clinical decision-making based on primary data and prioritisation of future research endeavours. PROSPERO REGISTRATION NUMBER: CRD42019133444.

13.
Cochrane Database Syst Rev ; 6: CD003506, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-31194882

RESUMO

BACKGROUND: Standard androgen suppression therapy (AST) using surgical or medical castration is considered a mainstay of advanced hormone-sensitive prostate cancer treatment. AST can be initiated early when disease is asymptomatic or deferred when patients suffer symptoms of disseminated prostate cancer. OBJECTIVES: To assess the effects of early versus deferred standard AST for advanced hormone-sensitive prostate cancer. SEARCH METHODS: For this Cochrane Review update, we performed a comprehensive search of multiple databases (CENTRAL, MEDLINE, Embase, Web of Science; last searched November 2018) and two clinical trial registers, with no restrictions on the language of publication or publication status. We also searched bibliographies of included studies and conference proceedings (last searched January 2019). SELECTION CRITERIA: We included all randomised controlled trials (RCTs) with a direct comparison of early versus deferred standard AST. We excluded all other study designs. Participants included had advanced hormone-sensitive prostate cancer receiving surgical or medical castration. DATA COLLECTION AND ANALYSIS: Two review authors independently classified studies and abstracted data. The primary outcomes were time to death of any cause and serious adverse events. Secondary outcomes were time to disease progression, time to death from prostate cancer, adverse events and quality of life. We performed statistical analyses using a random-effects model and assessed the certainty of evidence according to GRADE. We performed subgroup analyses for advanced but non-metastatic disease (T2-4/N+ M0), metastatic disease (M1), and prostate-specific antigen (PSA) relapse. MAIN RESULTS: We identified seven new RCTs since publication of the original review in 2002. In total, we included 10 RCTs.Primary outcomesEarly AST probably reduces the risk of death from any cause over time (hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.75 to 0.90; moderate-certainty evidence; 4767 participants). This corresponds to 57 fewer deaths (95% CI 80 fewer to 31 fewer) per 1000 participants at 5 years for the moderate risk group and 23 fewer deaths (95% CI 32 fewer to 13 fewer) per 1000 participants at 5 years in the low risk group. We downgraded for study limitations. Early versus deferred AST may have little or no effect on serious adverse events (risk ratio (RR) 1.05, 95% CI 0.95 to 1.16; low-certainty evidence; 10,575 participants) which corresponds to 6 more serious adverse events (6 fewer to 18 more) per 1000 participants. We downgraded the certainty of evidence for study limitations and selective reporting.Secondary outcomesEarly AST probably reduces the risk of death from prostate cancer over time (HR 0.69, 95% CI 0.57 to 0.84; moderate-certainty evidence). This corresponds to 62 fewer prostate cancer deaths per 1000 (95% CI 87 fewer to 31 fewer) at 5 years for the moderate risk group and 24 fewer death from prostate cancer (95% CI 34 fewer to 12 fewer) per 1000 men at 5 years in the low risk group. We downgraded the certainty of evidence for study limitations.Early AST may decrease the rate of skeletal events (RR 0.37, 95% CI 0.17 to 0.80; low-certainty evidence) corresponding to 23 fewer skeletal events per 1000 (95% CI 31 fewer to 7 fewer). We downgraded for study limitations and imprecision. It may also increase fatigue (RR 1.41, 95% CI 1.23 to 1.62; low-certainty evidence), corresponding to 31 more men with this complaint per 1000 (95% CI 18 more to 48 more). We downgraded for study limitations and imprecision. It may increase the risk of heart failure (RR 1.90, 95% CI 1.09 to 3.33; low-certainty evidence) corresponding to 27 more events per 1000 (95% CI 3 more to 69 more). We downgraded the certainty of evidence for study limitations and imprecision.Global quality of life is probably similar after two years as assessed with the EORTC QLQ-C30 (version 3.0) questionnaire (mean difference -1.56, 95% CI -4.50 to 1.38; moderate-certainty evidence) with higher scores reflecting better quality of life. We downgraded the certainty of evidence for study limitations. AUTHORS' CONCLUSIONS: Early AST probably extends time to death of any cause and time to death from prostate cancer. It may slightly decrease the rate of skeletal events. Rates of serious adverse events and quality of life may be similar. It may increase fatigue and may increase the risk of heart failure. Better quality trials would be particularly important to better understand the outcomes related to possible treatment-related harm, for which we only found low-certainty evidence.


Assuntos
Antígeno Prostático Específico , Neoplasias da Próstata , Progressão da Doença , Humanos , Masculino , Antígeno Prostático Específico/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
Stat Med ; 38(17): 3288-3303, 2019 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-31074072

RESUMO

The performance of statistical methods is frequently evaluated by means of simulation studies. In case of network meta-analysis of binary data, however, available data-generating models (DGMs) are restricted to either inclusion of two-armed trials or the fixed-effect model. Based on data-generation in the pairwise case, we propose a framework for the simulation of random-effect network meta-analyses including multiarm trials with binary outcome. The only one of the common DGMs used in the pairwise case, which is directly applicable to a random-effects network setting uses strongly restrictive assumptions. To overcome these limitations, we modify this approach and derive a related simulation procedure using odds ratios as effect measure. The performance of this procedure is evaluated with synthetic data and in an empirical example.

15.
J Natl Cancer Inst ; 111(9): 887-902, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31077329

RESUMO

BACKGROUND: Current guidelines recommend neoadjuvant therapy for patients with stage II or III rectal cancer. The addition of platinum derivatives to fluoropyrimidine-based chemoradiotherapy has been frequently investigated, but their role in this setting remains controversial. METHODS: PubMed, Cochrane Library, and Web of Science were systematically searched for randomized trials comparing chemoradiotherapy with or without platinum agents in stage II or III rectal cancer. Main outcome parameters were overall and disease-free survival, additional outcomes included pathological complete response, isolated local recurrence, distant recurrence, toxicity, and perioperative morbidity. Time-to-event data were pooled as hazard ratios (HRs) by the inverse variance method and binary outcomes as odds ratios (ORs) by the Peto method with their respective 95% confidence interval (CI). All statistical tests were two-sided. RESULTS: Ten randomized controlled trials with data on 5599 patients were included in the meta-analysis. Platinum derivatives did not statistically significantly improve overall survival (HR = 0.93, 95% CI = 0.82 to 1.05, P = .23), disease-free survival (HR = 0.91, 95% CI = 0.83 to 1.01, P = .07), or local recurrence (OR = 0.83, 95% CI = 0.66 to 1.05, P = .12). However, it led to a statistically significant increase of pathological complete response (OR = 1.31, 95% CI = 1.10 to 1.55, P = .002) and a statistically significant reduction of distant recurrence (OR = 0.78, 95% CI = 0.66 to 0.92, P = .004). Benefits were accompanied by higher rates of grade 3 or 4 toxicities. CONCLUSIONS: Intensified neoadjuvant chemoradiotherapy with the addition of platinum derivatives cannot be recommended routinely because it did not improve overall or disease-free survival and was associated with increased toxicity. It needs to be elucidated whether the benefits in distant recurrence and pathological complete response may be advantageous for selected high-risk patients.

16.
Eur J Prev Cardiol ; 26(10): 1035-1049, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30857429

RESUMO

BACKGROUND: Exercise-based cardiac rehabilitation (ebCR) often includes various psychological interventions for lifestyle change or distress management. However, the additional benefit of specific psychological interventions on depression, anxiety, quality of life, cardiac morbidity and cardiovascular or total mortality is not well investigated. DESIGN: Systematic review and meta-analysis. METHODS: Randomized controlled trials and controlled cohort trials published between January 1995 and October 2017 comparing ebCR with or without pre-specified psychosocial interventions were selected and evaluated on the basis of predefined inclusion and outcome criteria. RESULTS: Out of 15,373 records, 20 studies were identified, including 4450 patients with coronary artery disease (88.5%) or congestive heart failure (11.5%), respectively. Studies were of low to moderate quality and methodological heterogeneity was high. As compared with ebCR alone, additional psychological interventions for lifestyle change or distress management showed a trend to reduce depressive symptoms (standardized mean difference -0.13, 95% confidence interval (CI) -0.30; 0.05). Furthermore, during a follow-up of five years, distress management was associated with a trend to reduce cardiac morbidity (risk ratio 0.74, 95% CI 0.51; 1.07). There was no evidence for an additional impact of either psychological lifestyle change interventions or distress management on anxiety, quality of life, cardiovascular or total mortality. CONCLUSIONS: Specific psychological interventions offered during ebCR may contribute to a reduction of depressive symptoms and cardiac morbidity, but there remains considerable uncertainty under which conditions these interventions exert their optimal effects. (CRD42015025920).

17.
Z Kinder Jugendpsychiatr Psychother ; 47(4): 359-370, 2019 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-30326807

RESUMO

The diagnostics of autism spectrum disorder in children, adolescents and adults: Overview of the key questions and main results of the first part of the German AWMF-S3 - clinical guideline Abstract. Background: Autism spectrum disorders (ASD) include ICD-10 diagnoses of childhood autism, Asperger syndrome, and atypical autism; there is a lifetime prevalence of ~1 %. The aim of the evidence-based clinical guideline (AWMF-S3-Guideline) is to summarize the current evidence concerning diagnostic and therapeutic processes for professionals working in healthcare and social welfare and to provide consensus on clinical recommendations. The present study summarizes the most important results of the diagnostic part of this guideline. Method: The guideline group comprised 14 clinical and scientific expert associations from the German healthcare system, in addition to representatives of relatives and patients. Recommendations were based on results of a systematic literature search, data extraction, the evaluation of study quality, and, if possible, meta-analytic aggregation of included data in combination with the clinical expertise of the respective representatives. Consensus-based recommendations were determined via nominal group technique. Results: The AWMF-S3-Clinical Guideline, Diagnostic Part, summarizes current research on this topic. The main focus is put on the question of obligatory versus redundant diagnostic procedures. After a general introduction to the clinical picture of ASD, essential aspects like obtaining the medical history, the effective use of screening and diagnostic instruments, medical examination, the full diagnostic work-up as well as communicating the diagnostic results to relatives and patients are described in detail. We also conducted a meta-analysis on the stability of early diagnosis. Conclusion: This first part of the ASD guideline offers users the opportunity to inform themselves about the background of ASD as well as evidence-based and broadly consented information on the correct diagnostic process of ASD from infancy to adulthood.


Assuntos
Transtorno do Espectro Autista/diagnóstico , Guias de Prática Clínica como Assunto , Adolescente , Adulto , Síndrome de Asperger/diagnóstico , Síndrome de Asperger/epidemiologia , Transtorno do Espectro Autista/epidemiologia , Pesquisa Biomédica , Criança , Alemanha/epidemiologia , Humanos , Prevalência
18.
BMC Med Res Methodol ; 18(1): 128, 2018 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-30419827

RESUMO

BACKGROUND: Network meta-analysis is an extension of the classical pairwise meta-analysis and allows to compare multiple interventions based on both head-to-head comparisons within trials and indirect comparisons across trials. Bayesian or frequentist models are applied to obtain effect estimates with credible or confidence intervals. Furthermore, p-values or similar measures may be helpful for the comparison of the included arms but related methods are not yet addressed in the literature. In this article, we discuss how hypothesis testing can be done in a Bayesian network meta-analysis. METHODS: An index is presented and discussed in a Bayesian modeling framework. Simulation studies were performed to evaluate the characteristics of this index. The approach is illustrated by a real data example. RESULTS: The simulation studies revealed that the type I error rate is controlled. The approach can be applied in a superiority as well as in a non-inferiority setting. CONCLUSIONS: Test decisions can be based on the proposed index. The index may be a valuable complement to the commonly reported results of network meta-analyses. The method is easy to apply and of no (noticeable) additional computational cost.


Assuntos
Algoritmos , Teorema de Bayes , Modelos Teóricos , Metanálise em Rede , Simulação por Computador , Humanos , Reprodutibilidade dos Testes
19.
Syst Rev ; 7(1): 11, 2018 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-29357929

RESUMO

BACKGROUND: Neoadjuvant (chemo-)radiation has proven to improve local control compared to surgery alone, but this improvement did not translate into better overall or disease-specific survival. The addition of oxaliplatin to fluoropyrimidine-based neoadjuvant chemoradiotherapy holds the potential of positively affecting survival in this context since it has been proven effective in the palliative and adjuvant setting of colorectal cancer. Thus, the objective of this systematic review is to assess the efficacy, safety, and quality of life resulting from adding a platinum derivative to neoadjuvant single-agent fluoropyrimidine-based chemoradiotherapy in patients with Union for International Cancer Control stage II and III rectal cancer. METHODS: MEDLINE, Web of Science, and Cochrane Central Register of Controlled Trials will be systematically searched to identify all randomized controlled trials comparing single-agent fluoropyrimidine-based chemoradiotherapy to combined neoadjuvant therapy including a platinum derivative. Predefined data on trial design, quality, patient characteristics, and endpoints will be extracted. Quality of included trials will be assessed according to the Cochrane Risk of Bias Tool, and the GRADE recommendations will be applied to judge the quality of the resulting evidence. The main outcome parameter will be survival, but also treatment toxicity, perioperative morbidity, and quality of life will be assessed. DISCUSSION: The findings of this systematic review and meta-analysis will provide novel insights into the efficacy and safety of combined neoadjuvant chemoradiotherapy including a platinum derivative and may form a basis for future clinical decision-making, guideline evaluation, and research prioritization. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017073064.


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Neoadjuvante/métodos , Oxaliplatina/uso terapêutico , Neoplasias Retais/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Humanos , Qualidade de Vida , Neoplasias Retais/radioterapia , Sobrevida
20.
Urol Oncol ; 36(10): 448-458, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-28712790

RESUMO

OBJECTIVE: To systematically evaluate evidence on prognostic factors for tumor recurrence in patients with clinical stage I seminoma undergoing surveillance. METHODS: Systematic literature search conducted of Medline, Web of Science, Cochrane Library, and the conference proceedings of the ASCO, AUA, and EAU meetings (last search: October 2016), according to our prospectively registered protocol (PROSPERO registration number CRD42014009434). Identified records were reviewed according to the Cochrane Method Group of Prognosis Reviews recommendations and the PRISMA reporting guideline. Study quality was appraised with the Quality in Prognosis Studies (QUIPS) tool. RESULTS: Nineteen studies reporting on 26 potential prognostic factors were included in our analysis. Among the most frequently reported factors, tumor size (continuous or dichotomized) was significantly associated with relapse in 10/14 studies with a hazard ratio (HR) ranging from 1.33 (95% confidence interval [CI]: 1.14-1.56) to 3.17 (95% CI: 1.08-9.26). Rete testis invasion was significantly associated with relapse in only 4/13 studies with a HR ranging from 1.18 (95% CI: 0.92-1.51) to 1.36 (95% CI: 0.81-2.28). Lymphovascular invasion, young age, and preoperative HCG level had no association with relapse. Our findings are limited by heterogeneity of study designs, potential reporting bias, and moderate-to-poor study quality. CONCLUSION: In stage I seminoma, tumor size is the most valuable prognostic factor on which to base relapse risk and to counsel patients about adjuvant treatment. Large tumor size was defined quite inhomogenously among the included studies, so no distinct cutoff value for tumor size can be recommended. Other potential prognostic factors including rete testis invasion play a minor role in stage I seminoma.


Assuntos
Recidiva Local de Neoplasia/epidemiologia , Seminoma/patologia , Neoplasias Testiculares/patologia , Conduta Expectante , Humanos , Masculino , Prognóstico
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