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Introduction Obesity and related cardiometabolic comorbidities, including hypertension, dyslipidaemia, diabetes, metabolic dysfunction-associated steatotic liver disease and atherosclerotic cardiovascular disease, are increasingly prevalent among individuals with inflammatory bowel disease (IBD). These conditions influence disease activity, therapeutic response, surgical outcomes and overall quality of life, yet evidence remains fragmented. The M odulate O besity and relate D metabolic compl I cations F or Y ielding improvements in IBD outcomes (MODIFY-IBD) initiative aims to synthesise evidence and generate consensus recommendations to guide practice and future research in this area. This study describes a protocol for a structured evidence synthesis and Research ANd Development/University of California, Los Angeles (RAND/UCLA) Appropriateness Method (RUAM) consensus process. Methods and analysis We will conduct three systematic reviews and a structured evidence synthesis organised into three domains: (1) the impact of obesity on IBD outcomes, (2) the burden of cardiometabolic complications in IBD and (3) the management of overweight, obesity and cardiometabolic comorbidities in IBD. A multidisciplinary international panel of gastroenterologists, surgeons, endocrinologists, hepatologists, cardiologists and dietitians will assess each statement using the RAND/UCLA appropriateness method. Panellists will rate the appropriateness of each statement (only those that fall within their area of expertise) on a 1–9 scale (1–3=inappropriate, 4–6=uncertain and 7–9=appropriate), with medians rounded up (eg, 6.5=appropriate). Agreement will be assessed using the RAND Disagreement Index (DI<1.0=agreement). Ethics and dissemination This study will not involve direct patient participation, as it is based on evidence synthesis and expert consensus; therefore, formal research ethics committee approval will not be required. Patient representatives will contribute to the consensus process to provide contextual perspectives but no identifiable data will be collected. Findings will be disseminated through publication in peer-reviewed journals, presentation at major gastroenterology and IBD conferences and communication with professional societies. A lay summary and patient-friendly infographic will also be developed to facilitate translation of recommendations into clinical practice. PROSPERO registration numbers CRD420251178843: a systematic review of the impact of obesity on inflammatory bowel disease outcomes. CRD420251178799: a systematic review of cardiometabolic complications in inflammatory bowel disease. CRD420251174653: management of overweight, obesity and cardiometabolic comorbidities in inflammatory bowel disease: a systematic review.

Abstract We present a comprehensive global analysis of genetic variants associated with autosomal-dominant Alzheimer’s disease (ADAD). A total of 550 variants in the APP, PSEN1 and PSEN2 genes were identified, of which 279 were classified as pathogenic or likely pathogenic based on American College of Medical Genetics and Genomics and the Association for Molecular Pathology criteria, utilizing data from the Dominantly Inherited Alzheimer Network (DIAN), literature and public databases. Symptomatic age at onset (AAO) data were estimated for 227 of these variants, allowing detailed characterization of their frequency, pathogenicity and AAO. Importantly, 226 variants met eligibility criteria for inclusion in disease-modifying clinical trials. Furthermore, we demonstrated the predictive value of mean variant AAO and parental AAO in predicting symptomatic AAO, validated against converters who became symptomatic during follow-up in the DIAN Observational Study. This dataset provides critical insights into the global landscape of ADAD and reveals the genetic and AAO heterogeneity of ADAD variants while refining variant trial eligibility criteria.

Abstract Introduction Geriatric emergency department (ED) guidelines emphasize timely identification of delirium. This article updates previous diagnostic accuracy systematic reviews of history, physical examination, laboratory testing, and ED screening instruments for the diagnosis of delirium as well as test–treatment thresholds for ED delirium screening. Methods We conducted a systematic review to quantify the diagnostic accuracy of approaches to identify delirium. Studies were included if they described adults aged 60 or older evaluated in the ED setting with an index test for delirium compared with an acceptable criterion standard for delirium. Data were extracted and studies were reviewed for risk of bias. When appropriate, we conducted a meta‐analysis and estimated delirium screening thresholds. Results Full‐text review was performed on 55 studies and 27 were included in the current analysis. No studies were identified exploring the accuracy of findings on history or laboratory analysis. While two studies reported clinicians accurately rule in delirium, clinician gestalt is inadequate to rule out delirium. We report meta‐analysis on three studies that quantified the accuracy of the 4 A's Test (4AT) to rule in (pooled positive likelihood ratio [LR+] 7.5, 95% confidence interval [CI] 2.7–20.7) and rule out (pooled negative likelihood ratio [LR−] 0.18, 95% CI 0.09–0.34) delirium. We also conducted meta‐analysis of two studies that quantified the accuracy of the Abbreviated Mental Test‐4 (AMT‐4) and found that the pooled LR+ (4.3, 95% CI 2.4–7.8) was lower than that observed for the 4AT, but the pooled LR− (0.22, 95% CI 0.05–1) was similar. Based on one study the Confusion Assessment Method for the Intensive Care Unit (CAM‐ICU) is the superior instrument to rule in delirium. The calculated test threshold is 2% and the treatment threshold is 11%. Conclusions The quantitative accuracy of history and physical examination to identify ED delirium is virtually unexplored. The 4AT has the largest quantity of ED‐based research. Other screening instruments may more accurately rule in or rule out delirium. If the goal is to rule in delirium then the CAM‐ICU or brief CAM or modified CAM for the ED are superior instruments, although the accuracy of these screening tools are based on single‐center studies. To rule out delirium, the Delirium Triage Screen is superior based on one single‐center study.

AbstractObjectiveComputed tomography (CT) imaging is frequently obtained for recurrent abdominal pain after a prior emergency department (ED) evaluation. We evaluate the utility of repeat CT imaging following an indeterminate index CT in low‐risk abdominal pain adult ED patients.MethodsAn electronic search was designed for the patient‐intervention‐control‐outcome‐timing (PICOT) question: (P) adult patients with low‐risk, recurrent, and previously undifferentiated atraumatic abdominal pain presenting to the ED after an index‐negative CT within 12 months; (I) repeat CT versus (C) no repeat CT; for (O) abdominal surgery or other invasive procedure, mortality, identification of potentially life‐threatening diagnosis, and hospital and intensive care unit admission rates; and return ED visit (T), all within 30 days. Four reviewers independently selected evidence for inclusion and then synthesized the results around the most prevalent themes of repeat CT timing, diagnostic yield, ionizing radiation exposure, and predictors of repetitive imaging.ResultsAlthough 637 articles and abstracts were identified, no direct evidence was found. Thirteen documents were synthesized as indirect evidence. None of the indirect evidence defined a low‐risk subset of abdominal pain nor did investigators describe whether reimaging occurred for complaints similar to the initial ED evaluation. Included studies did not describe the index CT findings and some reported explanatory findings noted on the original CT for which repeat CTs might have been indicated. The time frame for a repeat CT ranged from hours to 1 year. The frequency of repeat CTs (2%–47%) varied across studies as did the yield of imaging to alter downstream clinical decision making (range = 5%–67%).ConclusionDue to the absence of direct evidence our scoping review is unable to provide high‐quality evidence‐based recommendations upon which to confidently base an imaging practice guideline. There is no evidence to support or refute performing a CT for low‐risk recurrent abdominal pain.