NEUROCOGNITION IN INDIVIDUALS AT HIGH FAMILIAL RISK FOR MAJOR DEPRESSIVE DISORDER

Neurocognitive deficits may qualify as vulnerability markers in individuals at risk for developing MDD. We examined the extent to which characteristic neurocognitive difficulties in MDD may be apparent in early to late adolescence in the offspring of a parent with MDD, as well as the extent to which other factors, such as a history of comorbid diagnoses (e.g., ADHD), a history of MDD, and a current depressive episode, might confound to these differences. Offspring of patients with MDD (n=184) and a healthy normative sample (n=88) were compared on measures assessing attention, working memory, impulse control, and visual memory. The two groups were compared using ANCOVA, including an estimate of intellectual ability as a covariate, examining the effect of offspring status on neuropsychological performance. Offspring had significantly lower working memory and visual memory performance than did the normative sample, even after adjustment for IQ differences. Offspring with current depression, a history of comorbid ADHD or comorbid PTSD had significantly lower attention and working memory performance than did other unaffected offspring. Offspring with past depressive episodes and those who had never been depressed did not differ in current neuropsychological performance. When offspring with ADHD, PTSD, or current depression were removed from the analysis, however, and scores were adjusted for IQ differences, offspring of a parent with MDD continued to differ from individuals in the normative sample in working memory, at all levels of estimated intelligence. Offspring of patients with MDD exhibited working memory weaknesses at all levels of basic estimated intellectual ability. Modest working memory deficiencies may be a risk factor for, or potential genetic marker of, susceptibility to MDD

Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

Background Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P < 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)