Genetic and environmental aspects in the association between attention-deficit hyperactivity disorder symptoms and binge-eating behavior in adults: A twin study

Background Prior research demonstrated that attention-deficit hyperactivity disorder (ADHD) is associated with binge-eating behavior, binge-eating disorder (BED), and bulimia nervosa (BN). The aim of this study was to investigate these associations in an adult twin population, and to determine the extent to which ADHD symptoms and binge-eating behavior share genetic and environmental factors. Methods We used self-reports of current ADHD symptoms and lifetime binge-eating behavior and associated characteristics from a sample of over 18 000 adult twins aged 20-46 years, from the population-based Swedish Twin Registry. Mixed-effects logistic regression was used to examine the association between ADHD and lifetime binge-eating behavior, BED, and BN. Structural equation modeling was used in 13 773 female twins to determine the relative contribution of genetic and environmental factors to the association between ADHD symptoms and binge-eating behavior in female adult twins. Results ADHD symptoms were significantly associated with lifetime binge-eating behavior, BED, and BN. The heritability estimate for current ADHD symptoms was 0.42 [95% confidence interval (CI) 0.41-0.44], and for lifetime binge-eating behavior 0.65 (95% CI 0.54-0.74). The genetic correlation was estimated as 0.35 (95% CI 0.25-0.46) and the covariance between ADHD and binge-eating behavior was primarily explained by genetic factors (91%). Non-shared environmental factors explained the remaining part of the covariance. Conclusions The association between adult ADHD symptoms and binge-eating behavior in females is largely explained by shared genetic risk factors

Assessing Childhood Maltreatment Exposure in Patients Without and With a Diagnosis of Substance Use Disorder

Objectives: Childhood maltreatment (CM), widely held as a risk factor for substance use disorders (SUDs), is commonly assessed using the Childhood Trauma Questionnaire (CTQ). Retrospective self-reports are, however, potentially subject to bias. We used a unique patient sample with prospectively documented CM to examine the performance of the CTQ and how this is affected by the presence of SUD. Methods: Analysis was based on a total of 104 individuals. Subjects with prospectively recorded CM were identified from a specialized childhood trauma unit in Linköping, Sweden (n = 55; 31 with SUD, 61% females; 24 without SUD, 71% females). Clinical controls had SUD but no CM (n = 25, 48% females). Healthy controls had neither SUD nor CM (n = 24, 54% females). We analyzed the agreement between retrospective CTQ scores and prospectively documented CM by κ analysis and assessed the performance of the CTQ to identify CM exposure using receiver operating characteristic (ROC) analysis. Results: Agreement between prospectively and retrospectively recorded CM exposure was poor for sexual abuse (36.6%, Cohen κ = 0.32, P = 0.008) and physical abuse (67.3%, κ = 0.35, P = 0.007). Overall CTQ performance was fair (ROC: area under the ROC curve = 0.78, optimal cutoff = 36.5, sensitivity = 0.65, specificity = 0.75). However, performance was excellent in the absence of SUD (area under the ROC curve = 0.93, cutoff = 32.0, sensitivity = 0.88, specificity = 0.88), but poor in participants with lifetime SUD (area under the ROC curve = 0.62, cutoff = 42.0, sensitivity = 0.60, specificity = 0.36). Conclusions: These data support the CTQ as a tool to assess CM exposure but suggest that it may be less useful in patients with SUD

Scoping Review on Use of Drugs Targeting Interleukin 1 Pathway in DIRA and DITRA

Deficiencies in interleukin (IL)-1 receptor (IL-R) antagonist (DIRA) and IL-36R antagonist (DITRA) are rare genetic autoinflammatory diseases related to alterations in antagonists of the IL-1 pathway. IL-1 antagonists may represent therapeutic alternatives. Here, we aim to provide a scoping review of knowledge on use of IL-1-targeting drugs in DIRA and DITRA. An a priori protocol was published, and the study was conducted using the methodology described in the Joanna Briggs Institute Reviewer's Manual and the recently published PRISMA Extension for Scoping Review statement. A three-step search using MEDLINE and EMBASE databases until March 2018 with additional hand searching was performed. Data charting was performed. The search, article selection, and data extraction were carried out by two researchers independently. Twenty-four studies on use of anti-IL-1 drugs were included [15 studies including patients with diagnosis of DIRA (n = 19) and 9 studies including patients with diagnosis of DITRA (n = 9)]. Most studies followed a multicenter observational design. Among all patients who received treatment with anti-IL-1 drugs, nine and four mutations in IL1RN and IL36RN were found, respectively. Patients with DIRA were treated with anakinra (n = 17), canakinumab (n = 2), or rinolacept (n = 6). All patients with DITRA were treated with anakinra, and only one case was also treated with canakinumab. Time-to-response frequencies were evaluated as immediate, short, and medium-long term for DIRA (17/17, 15/17, and 9/10, respectively) and DITRA (7/9, 3/9, and 2/9, respectively). Most DITRA patients in whom anti-IL-1 treatment failed experienced good response to anti-tumor necrosis factor alpha or anti-IL-12/23 drugs. The safety profiles of treatments were similar in both diseases. Evidence on use of anti-IL-1 drugs in DIRA and DITRA is scarce and based on observational studies. Larger studies with better methodological quality are needed to increase confidence in use of these drugs in patients with DIRA and DITRA

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)