A comprehensive evaluation of colonic mucosal isolates of Sutterella wadsworthensis from inflammatory bowel disease

Peer reviewedPublisher PD

Drug education in victorian schools (DEVS): the study protocol for a harm reduction focused school drug education trial

<p>Abstract</p> <p>Background</p> <p>This study seeks to extend earlier Australian school drug education research by developing and measuring the effectiveness of a comprehensive, evidence-based, harm reduction focused school drug education program for junior secondary students aged 13 to 15 years. The intervention draws on the recent literature as to the common elements in effective school curriculum. It seeks to incorporate the social influence of parents through home activities. It also emphasises the use of appropriate pedagogy in the delivery of classroom lessons.</p> <p>Methods/Design</p> <p>A cluster randomised school drug education trial will be conducted with 1746 junior high school students in 21 Victorian secondary schools over a period of three years. Both the schools and students have actively consented to participate in the study. The education program comprises ten lessons in year eight (13-14 year olds) and eight in year nine (14-15 year olds) that address issues around the use of alcohol, tobacco, cannabis and other illicit drugs. Control students will receive the drug education normally provided in their schools. Students will be tested at baseline, at the end of each intervention year and also at the end of year ten. A self completion questionnaire will be used to collect information on knowledge, patterns and context of use, attitudes and harms experienced in relation to alcohol, tobacco, cannabis and other illicit drug use. Multi-level modelling will be the method of analysis because it can best accommodate hierarchically structured data. All analyses will be conducted on an Intent-to-Treat basis. In addition, focus groups will be conducted with teachers and students in five of the 14 intervention schools, subsequent to delivery of the year eight and nine programs. This will provide qualitative data about the effectiveness of the lessons and the relevance of the materials.</p> <p>Discussion</p> <p>The benefits of this drug education study derive both from the knowledge gained by trialling an optimum combination of innovative, harm reduction approaches with a large, student sample, and the resultant product. The research will provide better understanding of what benefits can be achieved by harm reduction education. It will also produce an intervention, dealing with both licit and illicit drug use that has been thoroughly evaluated in terms of its efficacy, and informed by teacher and student feedback. This makes available to schools a comprehensive drug education package with prevention characteristics and useability that are well understood.</p> <p>Trial registration</p> <p>Australia and New Zealand Clinical Trials Register (ANZCTR): <a href="http://www.anzctr.org.au/ACTRN12612000079842.aspx">ACTRN12612000079842</a></p

Health care professionals' views on discussing sexual wellbeing with patients who have had a stroke: A qualitative study

OBJECTIVES: To examine the experiences of health care professionals discussing sexual wellbeing with patients who have had a stroke. DESIGN: In-depth qualitative interview study with purposive sampling and thematic analysis. PARTICIPANTS: 30 health care professionals purposively recruited to include different roles and settings along the stroke patient pathway in secondary and primary care. SETTING: Two hospitals and three general practices in the West Midlands, UK. RESULTS: Sexual wellbeing was a topic that participants did not raise with patients and was infrequently raised by patients. Barriers to raising discussion were on four levels: structural, health care professional, patient, and professional-patient interface. Barriers within these levels included: sexual wellbeing not present within hospital stroke policy; the perception that sexual wellbeing was not within participants' role; participants' concern that raising the issue could cause harm to the patient; and the views that discussion would be inappropriate with older people or unimportant to women. Resources exist to aid discussion but many participants were unaware of them, and most of those that were, did not use them routinely. CONCLUSIONS: Participants lacked motivation, ownership, and the confidence and skills to raise sexual wellbeing routinely after stroke. Similar findings have been reported in cancer care and other taboo subjects such as incontinence potentially resulting in a sub-optimal experience for patients. Normalisation of the inclusion of sensitive topics in discussions post-stroke does not seem to need significant structural intervention and simple changes such as information provision and legitimisation through consideration of the issue in standard care policies may be all that is required. The experiences recounted by professionals in this study suggest that such changes are needed now

Recommended practices for computerized clinical decision support and knowledge management in community settings: a qualitative study

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to identify recommended practices for computerized clinical decision support (CDS) development and implementation and for knowledge management (KM) processes in ambulatory clinics and community hospitals using commercial or locally developed systems in the U.S.</p> <p>Methods</p> <p>Guided by the Multiple Perspectives Framework, the authors conducted ethnographic field studies at two community hospitals and five ambulatory clinic organizations across the U.S. Using a Rapid Assessment Process, a multidisciplinary research team: gathered preliminary assessment data; conducted on-site interviews, observations, and field surveys; analyzed data using both template and grounded methods; and developed universal themes. A panel of experts produced recommended practices.</p> <p>Results</p> <p>The team identified ten themes related to CDS and KM. These include: 1) workflow; 2) knowledge management; 3) data as a foundation for CDS; 4) user computer interaction; 5) measurement and metrics; 6) governance; 7) translation for collaboration; 8) the meaning of CDS; 9) roles of special, essential people; and 10) communication, training, and support. Experts developed recommendations about each theme. The original Multiple Perspectives framework was modified to make explicit a new theoretical construct, that of Translational Interaction.</p> <p>Conclusions</p> <p>These ten themes represent areas that need attention if a clinic or community hospital plans to implement and successfully utilize CDS. In addition, they have implications for workforce education, research, and national-level policy development. The Translational Interaction construct could guide future applied informatics research endeavors.</p

Identification of sumoylation targets, combined with inactivation of SMT3, reveals the impact of sumoylation upon growth, morphology, and stress resistance in the pathogen Candida albicans

Peer reviewedPublisher PD

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p&lt;0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (&lt;1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (&lt;1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline