ObjectivesWe conducted a systematic literature review to assess the adverse event (AE) profile of paracetamol.MethodsWe searched Medline and Embase from database inception to 1 May 2013. We screened for observational studies in English, which reported mortality, cardiovascular, gastrointestinal (GI) or renal AEs in the general adult population at standard analgesic doses of paracetamol. Study quality was assessed using Grading of Recommendations Assessment, Development and Evaluation. Pooled or adjusted summary statistics were presented for each outcome.ResultsOf 1888 studies retrieved, 8 met inclusion criteria, and all were cohort studies. Comparing paracetamol use versus no use, of two studies reporting mortality one showed a dose–response and reported an increased relative rate of mortality from 0.95 (0.92 to 0.98) to 1.63 (1.58 to 1.68). Of four studies reporting cardiovascular AEs, all showed a dose–response with one reporting an increased risk ratio of all cardiovascular AEs from 1.19 (0.81 to 1.75) to 1.68 (1.10 to 2.57). One study reporting GI AEs reported a dose–response with increased relative rate of GI AEs or bleeds from 1.11 (1.04 to 1.18) to 1.49 (1.34 to 1.66). Of four studies reporting renal AEs, three reported a dose–response with one reporting an increasing OR of ≥30% decrease in estimated glomerular filtration rate from 1.40 (0.79 to 2.48) to 2.19 (1.4 to 3.43).DiscussionGiven the observational nature of the data, channelling bias may have had an important impact. However, the dose–response seen for most endpoints suggests a considerable degree of paracetamol toxicity especially at the upper end of standard analgesic doses.

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Clinical practice guidelines (CPGs) are used to support clinicians and patients in diagnostic and treatment decision-making. Along with patients’ preferences and values, and clinicians’ experience and judgment, practice guidelines are a critical component to ensure patients are getting the best care based on the most updated research findings. Most CPGs are based on systematic reviews of the treatment literature. Although most reviews are now restricted to randomized controlled trials, others may consider nonrandomized effectiveness trials. Despite a reliance on similar procedures and data, methodological decisions and the interpretation of the evidence by the guideline development panel can result in different recommendations. In this article, we will describe key methodological points for 5 recently released CPGs on the treatment of posttraumatic stress disorder in adults and highlight some of the differences in both the process and the subsequent recommendations.

research fellow 1 , Vanessa Delgado Nunes senior research fellow and guideline lead 1 , M Stephen Murphy clinical director for children's guidelines 1 , Steve Cunningham consultant and honorary reader in paediatric respiratory medicine 2 , on behalf of the guideline development group and technical team

As more complex meta-analytical techniques such as network and multivariate meta-analyses become increasingly common, further pressures are placed on reviewers to extract data in a systematic and consistent manner. Failing to do this appropriately wastes time, resources and jeopardises accuracy. This guide (data extraction for complex meta-analysis (DECiMAL)) suggests a number of points to consider when collecting data, primarily aimed at systematic reviewers preparing data for meta-analysis. Network meta-analysis (NMA), multiple outcomes analysis and analysis combining different types of data are considered in a manner that can be useful across a range of data collection programmes. The guide has been shown to be both easy to learn and useful in a small pilot study.Electronic supplementary materialThe online version of this article (doi:10.1186/s13643-016-0368-4) contains supplementary material, which is available to authorized users.