Patient focused registries can improve health, care, and science.

Eugene Nelson and colleagues call for registries of care data to be transformed into patient centred interactive learning systemsThis work is supported by funding from the Robert Wood Johnson Foundation (Grants: #71211 and 72313), the Cystic Fibrosis Foundation (Grant #OCONNO04Q10), and the Crohn’s and Colitis Foundation of America Quality of Care Initiative (Grant #3372). TSM was funded by the Multidisciplinary Clinical Research Center for Musculoskeletal Diseases at Dartmouth (P60 AR-062799, A. Tosteson, PI), sponsored by the National Institute for Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health. EE was funded by The Swedish Research Council for Health, Work Life and Welfare (#2014-4238). MDW is supported by a Wellcome Trust Senior Investigator award (WT09789).This is the final version of the article. It first appeared from BMJ Group via https://doi.org/10.1136/bmj.i331

Ecosystem resilience despite large-scale altered hydroclimatic conditions

Climate change is predicted to increase both drought frequency and duration, and when coupled with substantial warming, will establish a new hydroclimatological model for many regions. Large-scale, warm droughts have recently occurred in North America, Africa, Europe, Amazonia and Australia, resulting in major effects on terrestrial ecosystems, carbon balance and food security. Here we compare the functional response of above-ground net primary production to contrasting hydroclimatic periods in the late twentieth century (1975-1998), and drier, warmer conditions in the early twenty-first century (2000-2009) in the Northern and Southern Hemispheres. We find a common ecosystem water-use efficiency (WUE e: Above-ground net primary production/ evapotranspiration) across biomes ranging from grassland to forest that indicates an intrinsic system sensitivity to water availability across rainfall regimes, regardless of hydroclimatic conditions. We found higher WUE e in drier years that increased significantly with drought to a maximum WUE e across all biomes; and a minimum native state in wetter years that was common across hydroclimatic periods. This indicates biome-scale resilience to the interannual variability associated with the early twenty-first century drought - that is, the capacity to tolerate low, annual precipitation and to respond to subsequent periods of favourable water balance. These findings provide a conceptual model of ecosystem properties at the decadal scale applicable to the widespread altered hydroclimatic conditions that are predicted for later this century. Understanding the hydroclimatic threshold that will break down ecosystem resilience and alter maximum WUE e may allow us to predict land-surface consequences as large regions become more arid, starting with water-limited, low-productivity grasslands. © 2013 Macmillan Publishers Limited. All rights reserved

Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney.

Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation

« Nous ne pouvons pas continuer à en ajouter » : une étude de devis mixte afin d’explorer la faisabilité de la mise en œuvre d'un contenu coproduit de directives en matière de mouvement sur 24 heures

Background: Medical students must demonstrate competency in health promotion and illness prevention; however, movement behaviour promotion content is lacking in medical curricula. Canada’s 24-Hour Movement Guidelines (24HMG) present an opportunity to transform medical curricula to promote movement behaviours within a 24-hour paradigm. We previously co-produced a 24HMG curriculum map and 14 curriculum objectives at one Canadian medical school. The aim of this study was to gain consensus on the curriculum map and objectives among faculty and medical students and explore implementation determinants. Methods: This study followed a concurrent nested mixed methods design using a modified Delphi method to assess the level of (dis)agreement with map components followed by interviews to explore the implementability of the map. A preliminary survey was distributed to collect demographic and movement behaviour data, followed by three online modified Delphi surveys. Suggested improvements to the map were solicited through open-text boxes. Interviews were semi-structured and conducted online. Interview data were analyzed using content analysis guided by the Consolidated Framework for Implementation Research (CFIR) 2.0. Results: Consensus was reached on 156/180 items (86.7%) in Survey 1 (faculty, n = 6; students, n = 8), 49/51 items (96.1%) in Survey 2 (faculty, n = 4; students, n = 7), and 8/8 items (100%) in Survey 3 (faculty, n = 3; students, n = 7). Implementation determinants encompassed all five CFIR 2.0 domains, mostly the inner setting (e.g., culture, structural barriers). Conclusions: Reciprocity and open communication between medical schools and external change agents should be prioritized when co-producing curriculum change in the present landscape of inflation and medical professional burnout.Contexte : Les étudiants en médecine doivent démontrer leur compétence en matière de promotion de la santé et de prévention des maladies. Cependant, le contenu relatif à la promotion du mouvement fait défaut dans les programmes d'études médicales. Les directives canadiennes en matière de mouvement sur 24 heures offrent l'occasion de transformer les programmes d'études médicales afin de promouvoir le fait de bouger sur 24 heures. Nous avons précédemment coproduit une cartographie ainsi que 14 objectifs d’un curriculum favorisant le mouvement sur 24 heures  au sein d’une faculté de médecine au Canada. Le but de cette étude était d'obtenir un consensus sur cette cartographie et sur les objectifs du curriculum proposé parmi les professeurs et étudiants en médecine et d'explorer les déterminants de sa mise en œuvre. Méthodes : Cette étude a suivi un devis méthodologique mixte utilisant une méthode Delphi modifiée afin d’évaluer le niveau d’accord et de désaccord avec les composants de la cartographie, suivi d'entretiens pour explorer l’opérationnalisation de celle-ci. Un sondage préliminaire a été distribué pour recueillir des données démographiques et sur les comportements de mouvement, suivi de trois sondages Delphi modifiés en ligne. Les suggestions d'amélioration de la cartographie ont été collectées par le biais de questions à réponses courtes ouvertes. Les entrevues étaient semi-structurées et réalisées en ligne. Les données des entretiens ont été analysées à l'aide d'une analyse de contenu guidée par le Consolidated Framework for Implementation Research (CFIR) 2.0. Résultats : Un consensus a été atteint pour 156 des 180 points (86,7 %) dans l'enquête 1 (professeurs, n = 6 ; étudiants, n = 8), 49/51 points (96,1 %) dans l'enquête 2 (professeurs, n = 4 ; étudiants, n = 7), et 8/8 points (100 %) dans l'enquête 3 (professeurs, n = 3 ; étudiants, n = 7). Les déterminants de la mise en œuvre englobaient les cinq domaines du CFIR 2.0, concernant principalement l'environnement interne (par exemple, la culture, les obstacles structurels). Conclusions : La réciprocité et la communication ouverte entre les facultés de médecine et les agents de changement externes devraient être prioritaires lors de la coproduction d’un changement de curriculum dans le paysage actuel d’inflation et d‘épuisement professionnel des médecins

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Enhancing health equity considerations in guidelines : health equity extension of the GIN-McMaster Guideline Development Checklist

Background: Practice guidelines may reduce health inequities by addressing preventable and unjust differences in health. However, health equity considerations are often inadequately integrated into the guideline planning and development process. This article describes a pragmatic approach to enhancing health equity considerations within guidelines by introducing an extension to the GIN-McMaster Guideline Development Checklist (GDC). Methods: We reviewed the latest guidance on enhancing health equity considerations in guideline development to draft the checklist and deployed a global online survey from March 27th, 2024, to May 13th, 2024 to gather consensus. We conducted a methodological review of guideline development handbooks to identify best practices in health equity considerations. An advisory board comprised of diverse interest-holders informed the development of the checklist. We made revisions based on the survey feedback and review findings. Findings: We present 21 extension items spanning 16 of the 18 guideline development topics from the GIN-McMaster GDC. Key additions include planning for engagement with individuals experiencing inequities in guideline development activities, applying an equity lens, and considering health equity in recommendation formulation, dissemination and implementation strategies. This checklist gives value to lived experiences to enrich health equity assessments, complementing empirical evidence to inform guideline recommendations. Guideline developers should assess guideline sensitivity to health equity to determine resource prioritization for optimal implementation of the extension items. Interpretation: The GIN-McMaster health equity extension provides guidance for the streamlined integration of health equity considerations throughout the guideline development process. Using this tool alongside the original GIN-McMaster GDC may lead to more equitable and impactful guidelines. Funding: This project was partially funded by Public Health Agency of Canada. The funder was not involved in the conceptualization or design or the conduct of the project

A low mortality, high morbidity Reduced Intensity Status Epilepticus (RISE) model of epilepsy and epileptogenesis in the rat

Animal models of acquired epilepsies aim to provide researchers with tools for use in understanding the processes underlying the acquisition, development and establishment of the disorder. Typically, following a systemic or local insult, vulnerable brain regions undergo a process leading to the development, over time, of spontaneous recurrent seizures. Many such models make use of a period of intense seizure activity or status epilepticus, and this may be associated with high mortality and/or global damage to large areas of the brain. These undesirable elements have driven improvements in the design of chronic epilepsy models, for example the lithium-pilocarpine epileptogenesis model. Here, we present an optimised model of chronic epilepsy that reduces mortality to 1% whilst retaining features of high epileptogenicity and development of spontaneous seizures. Using local field potential recordings from hippocampus in vitro as a probe, we show that the model does not result in significant loss of neuronal network function in area CA3 and, instead, subtle alterations in network dynamics appear during a process of epileptogenesis, which eventually leads to a chronic seizure state. The model’s features of very low mortality and high morbidity in the absence of global neuronal damage offer the chance to explore the processes underlying epileptogenesis in detail, in a population of animals not defined by their resistance to seizures, whilst acknowledging and being driven by the 3Rs (Replacement, Refinement and Reduction of animal use in scientific procedures) principles

Prevalence of symptomatic toxicities for novel therapies in adult oncology trials: A scoping review

BACKGROUND: Patients' self-report of their symptoms can provide important data for the evaluation of treatment benefit and tolerability of oncology drugs. Contemporary treatment approaches, including immunotherapy and molecular targeted therapies, have unique toxicities based on their novel mechanisms of action. This scoping review aimed to summarize evidence from existing reviews and clinical practice guidelines to examine the type and prevalence of toxicities including symptomatic adverse events (sympAEs) for adult cancer patients to inform clinical care and therapeutic trials. METHODS: A systematic search of PubMed, Web of Science, and Embase was performed using predefined eligibility criteria. Thirty-one literature reviews and 3 clinical practice guidelines met inclusion criteria and were selected for review and data abstraction. RESULTS: Findings from this scoping review demonstrated several leading sympAEs that were reported across immunotherapy and targeted therapy drugs, including fatigue, diarrhea and rash. In addition to these more prevalent sympAEs, there were some less frequently reported class-specific sympAEs, which had potential for significant harm or disability to the patient if not properly identified and treated. Many studies reported toxicities as AEs or syndromes solely using data reported by clinicians without additional self-report from patients. CONCLUSION: We identified several core sympAEs experienced by patients participating in oncology trials using immunotherapy and targeted therapy agents, which has implications for future trial design and drug labeling. Future cancer trials should assess patient-reported sympAEs based on identified drug mechanism to inform the tolerability of these newer agents and enhance patient safety during trial participation and clinical care

Genetic predisposition to hypertension is associated with preeclampsia in European and Central Asian women

Preeclampsia is a serious complication of pregnancy, affecting both maternal and fetal health. In genome-wide association meta-analysis of European and Central Asian mothers, we identify sequence variants that associate with preeclampsia in the maternal genome at ZNF831/20q13 and FTO/16q12. These are previously established variants for blood pressure (BP) and the FTO variant has also been associated with body mass index (BMI). Further analysis of BP variants establishes that variants at MECOM/3q26, FGF5/4q21 and SH2B3/12q24 also associate with preeclampsia through the maternal genome. We further show that a polygenic risk score for hypertension associates with preeclampsia. However, comparison with gestational hypertension indicates that additional factors modify the risk of preeclampsia