Identifying unanswered questions and setting the agenda for future systematic research in Multiple Sclerosis. A worldwide, multi-stakeholder Priority Setting project.

Background: Eliciting the research priorities of people affected by a condition, carers and health care professionals can increase research value and reduce research waste. The Cochrane Multiple Sclerosis and Rare Disease of CNS Group, in collaboration with the Cochrane Neurological Sciences Field, launched a priority setting exercise with the aim of prioritizing pressing questions to ensure that future systematic reviews are as useful as possible to the people who need them, in all countries, regardless of their economic status.

Method: Sixteen high priority questions on different aspects of MS were developed by members of a multi-stakeholder priority setting Steering Group (SG).

Topical antibiotic prophylaxis to reduce respiratory tract infections and mortality in adults receiving mechanical ventilation.

Background: Patients treated with mechanical ventilation in intensive care units (ICUs) have a high risk of developing respiratory tract infections (RTIs). Ventilator-associated pneumonia (VAP) has been estimated to affect 5% to 40% of patients treated with mechanical ventilation for at least 48 hours. The attributable mortality rate of VAP has been estimated at about 9%.

GRADE EVIDENCE TO DECISION (EtD) FRAMEWORK FOR COVERAGE DECISIONS.

Objectives: Coverage decisions are decisions by third party payers about whether and how much to pay for technologies or services, and under what conditions. Given their complexity, a systematic and transparent approach is needed. The DECIDE (Developing and Evaluating Communication Strategies to Support Informed Decisions and Practice Based on Evidence) Project, a GRADE (Grading of Recommendations Assessment, Development and Evaluation) Working Group initiative funded by the European Union, has developed GRADE Evidence to Decision (EtD) framework for different types of decisions, including coverage ones.

Accuracy of serum procalcitonin for the diagnosis of sepsis in neonates and children with systemic inflammatory syndrome: a meta-analysis.

Background: A number of biomarkers have been studied for the diagnosis of sepsis in paediatrics, but no gold standard has been identified. Procalcitonin (PCT) was demonstrated to be an accurate biomarker for the diagnosis of sepsis in adults and showed to be promising in paediatrics. Our study reviewed the diagnostic accuracy of PCT as an early biomarker of sepsis in neonates and children with suspected sepsis.

Efficacy of hysteroscopy in improving reproductive outcomes of infertile couples: a systematic review and meta-analysis.

Background: The scientific community has been re-evaluating the clinical relevance of hysteroscopy in the diagnosis and treatment of uterine factors and its role in the infertility work-up, thanks to its potential capability to improve reproductive outcomes and reduce time to pregnancy.

Objective And Rationale: The objective of this systematic review and meta-analysis was to assess the efficacy of diagnostic and operative hysteroscopy in improving the live birth rate (LBR) of infertile women, with and without intrauterine abnormalities, at any stage of the infertility work-up.

Search Methods: PubMed, Embase, the Cochrane Library and the Clinical Trials Registry using Medical Subject Headings and free text terms were searched up to June 2014, without language or year restrictions.

Association of Immunotherapies With Outcomes in Relapsing-Remitting Multiple Sclerosis.

Clinical Question: What immunotherapies for multiple sclerosis are associated with the greatest benefit and highest risk of discontinuation due to adverse events in patients with relapsing-remitting multiple sclerosis?

Bottom Line: Alemtuzumab, natalizumab, and fingolimod were associated with the greatest benefit with regard to relapse prevention. Their association with prevention of disability worsening was unclear. Fingolimod was associated with a high risk of treatment discontinuation due to adverse events.

Risk of severe cardiotoxicity following treatment with trastuzumab: a meta-analysis of randomized and cohort studies of 29,000 women with breast cancer.

Trastuzumab prolongs survival in women with HER2-positive breast cancer, but may increase the risk of heart disease. The occurrence of severe cardiotoxicity, however, is not defined in real-life settings. We performed a meta-analysis of clinical trials and cohort studies to estimate the frequency of cardiotoxicities following trastuzumab treatment.

Atypical Antipsychotic Augmentation for Treatment-Resistant Depression: A Systematic Review and Network Meta-Analysis.

Background: Previous meta-analyses of atypical antipsychotics for depression were limited by few trials with direct comparisons between two treatments. We performed a network meta-analysis, which integrates direct and indirect evidence from randomized controlled trials (RCTs), to investigate the comparative efficacy and tolerability of adjunctive atypical antipsychotics for treatment-resistant depression (TRD).

Methods: Systematic searches resulted in 18 RCTs (total n = 4422) of seven different types and different dosages of atypical antipsychotics and a placebo that were included in the review.

Ethics and equity in research priority-setting: stakeholder engagement and the needs of disadvantaged groups.

A transparent and evidence-based priority-setting process promotes the optimal use of resources to improve health outcomes. Decision-makers and funders have begun to increasingly engage representatives of patients and healthcare consumers to ensure that research becomes more relevant. However, disadvantaged groups and their needs may not be integrated into the priority-setting process since they do not have a "political voice" or are unable to organise into interest groups.

Trastuzumab-containing regimens for metastatic breast cancer.

Background: Patients with breast cancer are classified as having cells that over-express the human epidermal growth factor receptor 2 (known as HER2-positive) or not (HER2-negative). Typically, patients with HER2-positive disease have a worse prognosis. Trastuzumab is a selective treatment that targets the HER2 pathway.

Are parents of children hospitalized with severe community-acquired pneumonia more satisfied with care when physicians allow them to share decisions on the antibiotic route?

Context And Objective: Despite convincing evidence that oral and injected amoxicillin have equal efficacy in children with severe community-acquired pneumonia (CAP), hospitalized children often receive injected antibiotics. To investigate whether shared decision-making (choosing the antibiotic route) influences parental satisfaction.

Design, Setting And Participants: In a one-year questionnaire-based study, we enrolled consecutive children hospitalized for CAP.

Speed of updating online evidence based point of care summaries: prospective cohort analysis.

Objective: To evaluate the ability of international point of care information summaries to update evidence relevant to medical practice.

Design: Prospective cohort bibliometric analysis.

Setting: Top five point of care information summaries (Clinical Evidence, EBMGuidelines, eMedicine, Dynamed, UpToDate) ranked for coverage of medical conditions, editorial quality, and evidence based methodology.

A review of online evidence-based practice point-of-care information summary providers.

Background: Busy clinicians need easy access to evidence-based information to inform their clinical practice. Publishers and organizations have designed specific tools to meet doctors' needs at the point of care.

Objective: The aim of this study was to describe online point-of-care summaries and evaluate their breadth, content development, and editorial policy against their claims of being "evidence-based.

Antibiotic prophylaxis to reduce respiratory tract infections and mortality in adults receiving intensive care.

Background: Pneumonia is an important cause of mortality in intensive care units (ICUs). The incidence of pneumonia in ICU patients ranges between 7% and 40%, and the crude mortality from ventilator-associated pneumonia may exceed 50%. Although not all deaths in patients with this form of pneumonia are directly attributable to pneumonia, it has been shown to contribute to mortality in ICUs independently of other factors that are also strongly associated with such deaths.

Compliance of clinical trial registries with the World Health Organization minimum data set: a survey.

Background: Since September 2005 the International Committee of Medical Journal Editors has required that trials be registered in accordance with the World Health Organization (WHO) minimum dataset, in order to be considered for publication. The objective is to evaluate registries' and individual trial records' compliance with the 2006 version of the WHO minimum data set.

Methods: A retrospective evaluation of 21 online clinical trial registries (international, national, specialty, pharmaceutical industry and local) from April 2005 to February 2007 and a cross-sectional evaluation of a stratified random sample of 610 trial records from the 21 registries.

Clinical evidence continuous medical education: a randomised educational trial of an open access e-learning program for transferring evidence-based information - ICEKUBE (Italian Clinical Evidence Knowledge Utilization Behaviour Evaluation) - study protocol.

Background: In an effort to ensure that all physicians have access to valid and reliable evidence on drug effectiveness, the Italian Drug Agency sponsored a free-access e-learning system, based on Clinical Evidence, called ECCE. Doctors have access to an electronic version and related clinical vignettes. Correct answers to the interactive vignettes provide Continuing Medical Education credits.

Using Clinical Evidence in a national continuing medical education program in Italy.

In an effort to ensure that physicians have access to reliable evidence on drug effectiveness and safety, the Italian Drug Agency launched a program to disseminate independent information.