Defining certainty of net benefit: a GRADE concept paper.

Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology is used to assess and report certainty of evidence and strength of recommendations. This GRADE concept article is not GRADE guidance but introduces certainty of net benefit, defined as the certainty that the balance between desirable and undesirable health effects is favourable. Determining certainty of net benefit requires considering certainty of effect estimates, the expected importance of outcomes and variability in importance, and the interaction of these concepts. Certainty of net harm is the certainty that the net effect is unfavourable. Guideline panels using or testing this approach might limit strong recommendations to actions with a high certainty of net benefit or against actions with a moderate or high certainty of net harm. Recommendations may differ in direction or strength from that suggested by the certainty of net benefit or harm when influenced by cost, equity, acceptability or feasibility.

Should empiric antibiotic therapy be withheld when aetiology of preterm birth is non-infectious? A protocol for a systematic review.

INTRODUCTION: Preterm birth (PTB) at <37 weeks of gestation is the leading cause of perinatal morbidity and mortality in developed countries. The traditional approach has been based on the assumption that PTB is primarily a result of intrauterine infection, which triggers preterm labour and puts the newborn at risk of early onset sepsis (EOS). We are currently experiencing a rise in prematurity that results from maternal and fetal diseases unrelated to infection. We have designed a systematic review to assess whether chemoprophylaxis should be withheld when the aetiology of preterm birth is non-infectious. METHODS AND ANALYSIS: Our study will focus on studies evaluating EOS in preterm infants. We will conduct a comprehensive search of literature available up to 28 February 2018. An information specialist will search for eligible studies in Medline (Ovid interface, 1948 and onwards), Embase (Ovid interface, 1980 onwards) and the Cochrane Central Register of Controlled Trials (Wiley interface, current issue). We will search databases and registries including records of ongoing research, conference proceedings and thesis (clinical trials, WHO International Clinical Trials Registry Platform). Two authors will independently extract data from eligible studies and assess risk of bias. For continuous outcomes, which follow discrete distribution, mean difference will be calculated. Dichotomous data will be presented using risk ratios, while count data will be expressed using rate ratios. Time-to-event outcomes will be reported as HRs. All estimates will be presented together with 95% CI. Studies comparable with respect to methodology and reporting the same outcomes will be combined in a meta-analysis. ETHICS AND DISSEMINATION: Our systematic review does not require approval from the research and ethics board. We will use the findings to prepare a future multicentre randomised control trial in order to establish safe and adequate antibiotics policies for preterm infants, based on the aetiology of PTB. PROSPERO REGISTRATION NUMBER: CRD42016029707.

Comparative Effectiveness and Harms of Intraoperative Transesophageal Echocardiography in Noncardiac Surgery: A Systematic Review.

Intraoperative use of transesophageal echocardiography (TEE) has become commonplace in high-risk noncardiac surgeries but the balance of benefits and harms remains unclear. This systematic review investigated the comparative effectiveness and harms of intraoperative TEE in noncardiac surgery. We searched Ovid MEDLINE, PubMed, EMBASE, and the Cochrane Library from 1946 to March 2017. Two reviewers independently screened the literature for eligibility. Studies were assessed for the risk of selection bias, confounding, measurement bias, and reporting bias. Three comparative and 13 noncomparative studies were included. Intraoperative TEE was employed in a total of 1912 of 3837 patients. Studies had important design limitations. Data were not amenable to quantitative synthesis due to clinical and methodological diversity. Reported incidence of TEE complications ranged from 0% to 1.7% in patients undergoing various procedures (5 studies, 540 patients). No serious adverse events were observed for mixed surgeries (2 studies, 197 patients). Changes in surgical or medical management attributable to the use of TEE were noted in 17% to 81% of patients (7 studies, 558 patients). The only randomized trial of intraoperative TEE was grossly underpowered to detect meaningful differences in 30-day postoperative outcomes. There is lack of high-quality evidence of effectiveness and harms of intraoperative TEE in the management of non-cardiac surgeries. Evidence, however, indicates timely evaluation of cardiac function and structure, and hemodynamics. Future studies should be comparative evaluating confounder-adjusted impact on both intraoperative and 30-day postoperative clinical outcomes.

Perioperative use of pregabalin for acute pain-a systematic review and meta-analysis.

Evidence supporting postoperative pain management using pregabalin as an adjunct intervention across various surgical pain models is lacking. The objective of this systematic review was to evaluate "model-specific" comparative effectiveness and harms of pregabalin following a previously published systematic review protocol. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from inception through August 2013. Data were screened and single extraction with independent verification and dual risk of bias assessment was performed. Quality of evidence (QoE) was rated using the GRADE approach. Primary outcomes were pain relief at rest and on movement and reduction in postoperative analgesic consumption. A total of 1423 records were screened, and 43 studies were included. Perioperative pregabalin resulted in: 16% (95% confidence interval [CI], 9%-21%) reduction in analgesic consumption (moderate QoE, 24 trials) and a small reduction in the magnitude of pain in surgeries associated with pronociceptive pain. Per 1000 patients, 10 more will experience blurred vision (95% CI, 5-20 more; moderate QoE, 17 trials) and 41 more sedation (95% CI, 13-77 more, 17 trials). To prevent 1 case of perioperative nausea and vomiting, the number needed to treat is 11 (95% CI: 7-28, 25 trials). Inadequate evidence addressed outcomes of enhanced recovery and serious harms. Pregabalin analgesic effectiveness is largely restricted to surgical procedures associated with pronociceptive mechanisms. The clinical significance of observed pregabalin benefits must be weighed against the uncertainties about serious harms and enhanced recovery to inform the careful selection of surgical patients. Recommendations for future research are proposed.