BackgroundStarting in the late 1990s, the pharmaceutical industry sought to increase prescribing of opioids for chronic non-cancer pain. Influencing the content of clinical practice guidelines may have been one strategy industry employed. In this study we assessed potential risk of bias from financial conflicts of interest with the pharmaceutical industry in guidelines for opioid prescribing for chronic non-cancer pain published between 2007 and 2013, the peak of opioid prescribing. MethodsWe used the Guideline Panel Review (GPR) to appraise the guidelines included in the 2014 systematic review and critical appraisal by Nuckols et al. These were English language opioid prescribing guidelines for adults with chronic non-cancer pain published between July 2007 and July 2013, the peak of opioid prescribing. The GPR assigns red flags to items known to introduce potential bias from financial conflicts of interest. We operationalized the GPR by creating specific definitions for each red flag. Two reviewers independently evaluated each guideline. Disagreements were resolved with discussion. We also compared our score to the critical appraisal scores for overall quality from the study by Nuckols et al. ResultsWe appraised 13 guidelines, which received 43 red flags in total. Guidelines had 3.3 red flags on average (out of a possible seven) with range from one to six. Four guidelines had missing information, so red flags may be higher than reported. The guidelines with the

Objective: Genome sequencing (GS >30x) is beginning to be adopted as a comprehensive genome-wide test for the diagnosis of rare disease in the post-natal setting. Recent studies demonstrated the utility of exome sequencing (ES) in prenatal diagnosis, we investigate the potential benefits for GS to act as a comprehensive prenatal test for diagnosis of fetal abnormalities. Methods:We performed GS on a prospective cohort of 37 singleton fetuses with ultrasound-identified structural abnormalities undergoing invasive prenatal testing.GS was performed in parallel with standard diagnostic testing, and the prioritized variants were classified according to ACMG guidelines and reviewed by a panel of board-certified laboratory and clinical geneticists.Results: Diagnostic sequence variants were identified in 5 fetuses (14%), with pathogenic variants found in NIPBL, FOXF1, RERE, AMMECR1, and FLT4. A further 7 fetuses (19%) had variants of uncertain significance (VUS) that may explain the phenotypes. Importantly, GS also identified all pathogenic variants reported by clinical microarray (2 CNVs, 5%). Conclusion:Prenatal GS offered diagnoses (sequence variants and CNVs) in 19% of fetuses with structural anomalies. GS has the potential of replacing multiple consecutive tests, including microarray, gene panels, and WES, to provide the most comprehensive analysis in a timely manner necessary for prenatal diagnosis. Key pointsWhat's already known about this topic? � Current prenatal diagnostic protocol in Canada includes rapid aneuploidy detection (RAD) followed by microarray analysis.� The diagnostic yield of Exome sequencing in fetuses with ultrasound abnormalities and negative results by RAD and CMA is 8.5%-10%. However, the clinical utility of genome sequencing in prenatal settings is not established.

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Background: Postoperative atrial fibrillation (POAF) is the most common complication after cardiac surgery; it is associated with morbidity and mortality. We undertook this review to compare the effects of rhythm vs. rate control in this population. Methods: We searched MEDLINE, Embase and CENTRAL to March 2023. We included randomized trials and observational studies comparing rhythm to rate control in cardiac surgery patients with POAF. We used a random-effects model to meta-analyze data and rated the quality of evidence using GRADE. Results: From 8,110 citations, we identified 8 randomized trials (990 patients). Drug regimens used for rhythm control included amiodarone in four trials, other class III anti-arrhythmics in one trial, class I anti-arrhythmics in four trials and either a class I or III anti-arrhythmic in one trial. Rhythm control compared to rate control did not result in a significant difference in length of stay (mean difference −0.8 days; 95% CI −3.0 to +1.4, I2 = 97%), AF recurrence within 1 week (130 events; risk ratio [RR] 1.1; 95%CI 0.6–1.9, I2 = 54%), AF recurrence up to 1 month (37 events; RR 0.9; 95%CI 0.5–1.8, I2 = 0%), AF recurrence up to 3 months (10 events; RR 1.0; 95%CI 0.3–3.4, I2 = 0%) or mortality (25 events; RR 1.6; 95%CI 0.7–3.5, I2 = 0%). Effect measures from seven observational studies (1428 patients) did not differ appreciably from those in randomized trials. Conclusions: Although atrial fibrillation is common after cardiac surgery, limited low-quality data guide its management. Limited available evidence suggests no clear advantage to either rhythm or rate control. A large-scale randomized trial is needed to inform this important clinical question.

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