Defining predictors of responsiveness to advanced therapies in Crohn's disease and ulcerative colitis: protocol for the IBD-RESPONSE and nested CD-metaRESPONSE prospective, multicentre, observational cohort study in precision medicine.

INTRODUCTION: Characterised by chronic inflammation of the gastrointestinal tract, inflammatory bowel disease (IBD) symptoms including diarrhoea, abdominal pain and fatigue can significantly impact patient's quality of life. Therapeutic developments in the last 20 years have revolutionised treatment. However, clinical trials and real-world data show primary non-response rates up to 40%. A significant challenge is an inability to predict which treatment will benefit individual patients.Current understanding of IBD pathogenesis implicates complex interactions between host genetics and the gut microbiome. Most cohorts studying the gut microbiota to date have been underpowered, examined single treatments and produced heterogeneous results. Lack of cross-treatment comparisons and well-powered independent replication cohorts hampers the ability to infer real-world utility of predictive signatures.IBD-RESPONSE will use multi-omic data to create a predictive tool for treatment response. Future patient benefit may include development of biomarker-based treatment stratification or manipulation of intestinal microbial targets. IBD-RESPONSE and downstream studies have the potential to improve quality of life, reduce patient risk and reduce expenditure on ineffective treatments. METHODS AND ANALYSIS: This prospective, multicentre, observational study will identify and validate a predictive model for response to advanced IBD therapies, incorporating gut microbiome, metabolome, single-cell transcriptome, human genome, dietary and clinical data. 1325 participants commencing advanced therapies will be recruited from ~40 UK sites. Data will be collected at baseline, week 14 and week 54. The primary outcome is week 14 clinical response. Secondary outcomes include clinical remission, loss of response in week 14 responders, corticosteroid-free response/remission, time to treatment escalation and change in patient-reported outcome measures. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Wales Research Ethics Committee 5 (ref: 21/WA/0228). Recruitment is ongoing. Following study completion, results will be submitted for publication in peer-reviewed journals and presented at scientific meetings. Publications will be summarised at www.ibd-response.co.uk. TRIAL REGISTRATION NUMBER: ISRCTN96296121.

Teamwork Is Associated with Reduced Hospital Staff Burnout at Military Treatment Facilities: Findings from the 2019 Department of Defense Patient Safety Culture Survey.

BACKGROUND: A National Academy of Medicine report emphasizes the importance of creating positive work environments to address the negative effects of burnout on health care workers. The purpose of this investigation was to determine the scope of burnout among military hospital personnel and explore the relationship between teamwork, burnout, and patient safety culture. METHODS: A logistic regression analysis investigated the relationship between teamwork and burnout using the 2019 US Department of Defense Patient Safety Culture Survey data from 15,838 military hospital workers. Additional regressions investigated teamwork/burnout relationships among individual work areas and staff positions. RESULTS: About one third of respondents (34.4%) reported experiencing burnout. Work areas most likely to report burnout included many different/other work areas (43.4%), pharmacy (41.8%), and labor and delivery/obstetrics (41.8%). Staff positions most likely to report burnout included pharmacy/pharmacists (39.7%), assistants/technicians/therapists (38.1%), and nurses/nursing (37.6%). Analysis revealed an association between lower burnout and high teamwork, both within (odds ratio [OR] 0.54, 95% confidence interval [CI] 0.48-0.60) and across (OR 0.64, 95% CI 0.57-0.72) units. Within-unit teamwork was associated with reduced odds of burnout across almost all work areas and staff positions, with the greatest odds reduction among personnel working in emergency (OR 0.25, 95% CI 0.14-0.43), radiology (OR 0.41, 95% CI 0.20-0.83), and labor and delivery/obstetrics (OR 0.42, 95% CI 0.27-0.65); and physicians/medical staff (OR = 0.44, 95% CI: 0.28-0.69), other staff positions (OR 0.48, 95% CI 0.28-0.81), and assistants/technicians/therapists (OR 0.58, 95% CI 0.46-0.73). CONCLUSION: Effective teamwork may reduce burnout in hospital workers. This association between teamwork (particularly teamwork within units) and burnout was found in all work areas, even in those with the highest levels of self-reported workplace chaos. Greater adoption of workplace interventions focused on improving teamwork, such as TeamSTEPPS, is warranted.

Conservation of a pH-sensitive structure in the C-terminal region of spider silk extends across the entire silk gene family.

Spiders produce multiple silks with different physical properties that allow them to occupy a diverse range of ecological niches, including the underwater environment. Despite this functional diversity, past molecular analyses show a high degree of amino acid sequence similarity between C-terminal regions of silk genes that appear to be independent of the physical properties of the resulting silks; instead, this domain is crucial to the formation of silk fibers. Here, we present an analysis of the C-terminal domain of all known types of spider silk and include silk sequences from the spider Argyroneta aquatica, which spins the majority of its silk underwater. Our work indicates that spiders have retained a highly conserved mechanism of silk assembly, despite the extraordinary diversification of species, silk types and applications of silk over 350 million years. Sequence analysis of the silk C-terminal domain across the entire gene family shows the conservation of two uncommon amino acids that are implicated in the formation of a salt bridge, a functional bond essential to protein assembly. This conservation extends to the novel sequences isolated from A. aquatica. This finding is relevant to research regarding the artificial synthesis of spider silk, suggesting that synthesis of all silk types will be possible using a single process.