A Systematic Review of the Efficacy and Toxicity of Brachytherapy Boost Combined with External Beam Radiotherapy for Nonmetastatic Prostate Cancer.

Context: The optimum use of brachytherapy (BT) combined with external beam radiotherapy (EBRT) for localised/locally advanced prostate cancer (PCa) remains uncertain.

Objective: To perform a systematic review to determine the benefits and harms of EBRT-BT.

Evidence Acquisition: Ovid MEDLINE, Embase, and EBM Reviews-Cochrane Central Register of Controlled Trials databases were systematically searched for studies published between January 1, 2000 and June 7, 2022, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement.

Developing a topic-based repository of clinical trial individual patient data: experiences and lessons learned from a pilot project.

Background: Building a dataset of individual participant data (IPD) for meta-analysis represents considerable research investment as well as collaboration across multiple institutions and researchers. Making arrangements to curate and share the dataset beyond the IPD meta-analysis project for which it was established, for reuse in future research projects, would maximise the value of this investment.

Methods: Our aim was to establish the Cochrane repository for individual patient data from clinical trials in pregnancy and childbirth (CRIB) as an example of how an IPD repository could become part of Cochrane infrastructure.

A guide on meta-analysis of time-to-event outcomes using aggregate data in vascular and endovascular surgery.

Background: Time-to-event outcomes measure not only whether but also when an event happens. They are commonly used to evaluate vascular therapies, where the events of interest include disease recurrence (eg, loss of graft patency), reintervention (eg, target lesion revascularization), or death. Meta-analyses of published time-to-event outcomes are most appropriately measured by hazard ratios (HR).

Individualised prediction of psychosis in individuals meeting at-risk mental state (ARMS) criteria: protocol for a systematic review of clinical prediction models.

Background: Psychotic disorders affect about 3% of the population worldwide and are associated with high personal, social and economic costs. They tend to have their first onset in adolescence. Increasing emphasis has been placed on early intervention to detect illness and minimise disability.

The efficacy of interventions for test-anxious university students: A meta-analysis of randomized controlled trials.

Test anxiety (TA) is highly distressing and can significantly undermine academic performance. Many randomized controlled trials (RCTs) of interventions for university students with TA have been conducted, but there has been no systematic review of their efficacy. This meta-analysis examines the efficacy of interventions for test-anxious university students in: (i) reducing TA, and (ii) improving academic performance.

A PQM-1-Mediated Response Triggers Transcellular Chaperone Signaling and Regulates Organismal Proteostasis.

In metazoans, tissues experiencing proteotoxic stress induce "transcellular chaperone signaling" (TCS) that activates molecular chaperones, such as hsp-90, in distal tissues. How this form of inter-tissue communication is mediated to upregulate systemic chaperone expression and whether it can be utilized to protect against protein misfolding diseases remain open questions. Using C.

Exploring changes over time and characteristics associated with data retrieval across individual participant data meta-analyses: systematic review.

 To investigate whether the success rate of retrieving individual participant data (IPD) for use in IPD meta-analyses has increased over time, and to explore the characteristics associated with IPD retrieval. Systematic review of published IPD meta-analyses, supplemented by a reflection of the Cochrane Epilepsy Group's 20 years' experience of requesting IPD. Medline, CENTRAL, Scopus, Web of Science, CINAHL Plus, and PsycINFO.

Reporting of harms outcomes: a comparison of journal publications with unpublished clinical study reports of orlistat trials.

Background: The quality of harms reporting in journal publications is often poor, which can impede the risk-benefit interpretation of a clinical trial. Clinical study reports can provide more reliable, complete, and informative data on harms compared to the corresponding journal publication. This case study compares the quality and quantity of harms data reported in journal publications and clinical study reports of orlistat trials.

Governing drug use through partnerships: Towards a genealogy of government/non-government relations in drug policy.

Drug policy in Australia is underpinned by the idea of partnerships wherein the non-government sector is one important partner in both delivering services and contributing to policy and decision-making processes. This article presents a genealogy of the concept of government/non-government 'partnerships', tracing its emergence and development within drug policy discourse in Australia. We find that the rise of neo-liberal policies since the 1980s has been a key factor facilitating the emergence of government/non-government 'partnerships' rhetoric in drug policy.

Women's Health in Queensland Prisons.

Internationally, best practice for prison health care recommends transferring health service provision from corrections to health authorities. Although it is expected that this change will result in improved health care, there is little evidence of evaluation. This article used qualitative interviews with health service providers to gain insight into the health needs of women's prisons in Queensland, Australia, both prior to and after the transition in health care service provision.

Individual Participant Data (IPD) Meta-analyses of Randomised Controlled Trials: Guidance on Their Use.

Jayne Tierney and colleagues offer guidance on how to spot a well-designed and well-conducted individual participant data meta-analysis.

Interventions to improve recruitment and retention in clinical trials: a survey and workshop to assess current practice and future priorities.

Background: Despite significant investment in infrastructure many trials continue to face challenges in recruitment and retention. We argue that insufficient focus has been placed on the development and testing of recruitment and retention interventions.

Methods: In this current paper, we summarize existing reviews about interventions to improve recruitment and retention.

External validation of a prognostic model for seizure recurrence following a first unprovoked seizure and implications for driving.

Objective: In the United Kingdom and other European Union countries guidelines for driving following a first unprovoked seizure require the risk of another seizure in the next year to be less than 20%. Using data from one clinical trial, we previously developed a prognostic model to inform driving guidelines. The objective of this work is to externally validate our published model and demonstrate its generalisability.

Patient-level compared with study-level meta-analyses demonstrate consistency of D-dimer as predictor of venous thromboembolic recurrences.

Objective: We compared the performance of aggregate data (AD)--based and individual patient data (IPD)-based meta-analyses to synthesize evidence on the ability of D-dimer to distinguish recurrence risk in patients with unprovoked venous thromboembolism (VTE) who stopped anticoagulation.

Study Design And Setting: We compared the results of the published AD-based rate ratio of VTE recurrence for positive vs. negative D-dimer, estimated by a mixed-effect Poisson model, with those of the IPD-based hazard ratio obtained by a Cox regression stratified by trial.

Combining individual patient data and aggregate data in mixed treatment comparison meta-analysis: Individual patient data may be beneficial if only for a subset of trials.

Background: Individual patient data (IPD) meta-analysis is the gold standard. Aggregate data (AD) and IPD can be combined using conventional pairwise meta-analysis when IPD cannot be obtained for all relevant studies. We extend the methodology to combine IPD and AD in a mixed treatment comparison (MTC) meta-analysis.

Prognostic factors for time to treatment failure and time to 12 months of remission for patients with focal epilepsy: post-hoc, subgroup analyses of data from the SANAD trial.

Background: Epilepsy is a heterogeneous disorder, with outcomes ranging from immediate remission after taking a first antiepileptic drug to frequent unremitting seizures with multiple treatment failures. Few prognostic models enable prediction of outcome; we therefore aimed to use data from the SANAD study to predict outcome overall and for patients receiving specific treatments.

Methods: The SANAD study was a randomised controlled trial in which standard antiepileptic drugs were compared with new treatments.

Randomised Phase I/II trial assessing the safety and efficacy of radiolabelled anti-carcinoembryonic antigen I(131) KAb201 antibodies given intra-arterially or intravenously in patients with unresectable pancreatic adenocarcinoma.

Background: Advanced pancreatic cancer has a poor prognosis, and the current standard of care (gemcitabine based chemotherapy) provides a small survival advantage. However the drawback is the accompanying systemic toxicity, which targeted treatments may overcome. This study aimed to evaluate the safety and tolerability of KAb201, an anti-carcinoembryonic antigen monoclonal antibody, labelled with I(131) in pancreatic cancer (ISRCTN 16857581).

Gemcitabine based combination chemotherapy in advanced pancreatic cancer-indirect comparison.

Background: Recent meta-analyses have found a survival advantage with gemcitabine based combinations over single agent gemcitabine in patients with advanced pancreatic cancer. There is paucity of evidence in the form of direct head-to-head randomised controlled trials to determine which combinations are to be preferred.

Method: Using the adjusted indirect comparison method proposed by Bucher et al, we have assessed randomised controlled trials of four gemcitabine based combinations namely gemcitabine plus a platinum compound or 5-fluorouracil or irinotecan or capecitabine.

Meta-analyses of chemotherapy for locally advanced and metastatic pancreatic cancer.

Purpose: There are a large number of randomized controlled trials involving chemotherapy in the management of advanced pancreatic cancer. Several chemotherapeutic agents, either alone or in combination with other chemotherapy or novel agents, have been used. The aim of these meta-analyses was to examine the different therapeutic approaches, and the comparisons examined were as follows: chemotherapy versus best supportive care; fluorouracil (FU) versus FU combination chemotherapy; gemcitabine versus FU; and gemcitabine versus gemcitabine combination chemotherapy.

Importance of competing risks in the analysis of anti-epileptic drug failure.

Background: Retention time (time to treatment failure) is a commonly used outcome in antiepileptic drug (AED) studies.

Methods: Two datasets are used to demonstrate the issues in a competing risks analysis of AEDs. First, data collection and follow-up considerations are discussed with reference to information from 15 monotherapy trials.

The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy: an unblinded randomised controlled trial.

Background: Valproate is widely accepted as a drug of first choice for patients with generalised onset seizures, and its broad spectrum of efficacy means it is recommended for patients with seizures that are difficult to classify. Lamotrigine and topiramate are also thought to possess broad spectrum activity. The SANAD study aimed to compare the longer-term effects of these drugs in patients with generalised onset seizures or seizures that are difficult to classify.

The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled trial.

Background: Carbamazepine is widely accepted as a drug of first choice for patients with partial onset seizures. Several newer drugs possess efficacy against these seizure types but previous randomised controlled trials have failed to inform a choice between these drugs. We aimed to assess efficacy with regards to longer-term outcomes, quality of life, and health economic outcomes.

An overview of methods and empirical comparison of aggregate data and individual patient data results for investigating heterogeneity in meta-analysis of time-to-event outcomes.

Combining the results of individual studies using meta-analysis may be undertaken using either aggregate data (AD) or individual patient data (IPD). In any meta-analysis it is important to consider statistical heterogeneity between studies. Potential sources of heterogeneity can be explored using regression models with either AD or IPD.