The COVID-19 Pandemic and Physical Activity

The SARS-CoV-2-caused COVID-19 pandemic has resulted in a devastating threat to human society in terms of health, economy, and lifestyle. Although the virus usually first invades and infects the lung and respiratory track tissue, in extreme cases, almost all major organs in the body are now known to be negatively impacted often leading to severe systemic failure in some people. Unfortunately, there is currently no effective treatment for this disease. Pre-existing pathological conditions or comorbidities such as age are a major reason for premature death and increased morbidity and mortality. The immobilization due to hospitalization and bed rest and the physical inactivity due to sustained quarantine and social distancing can downregulate the ability of organs systems to resist to viral infection and increase the risk of damage to the immune, respiratory, cardiovascular, musculoskeletal systems and the brain. The cellular mechanisms and danger of this "second wave" effect of COVID-19 to the human body, along with the effects of aging, proper nutrition, and regular physical activity, are reviewed in this editorial article

Identifying the domains of context important to implementation science: a study protocol

Background There is growing recognition that “context” can and does modify the effects of implementation interventions aimed at increasing healthcare professionals’ use of research evidence in clinical practice. However, conceptual clarity about what exactly comprises “context” is lacking. The purpose of this research program is to develop, refine, and validate a framework that identifies the key domains of context (and their features) that can facilitate or hinder (1) healthcare professionals’ use of evidence in clinical practice and (2) the effectiveness of implementation interventions. Methods/design A multi-phased investigation of context using mixed methods will be conducted. The first phase is a concept analysis of context using the Walker and Avant method to distinguish between the defining and irrelevant attributes of context. This phase will result in a preliminary framework for context that identifies its important domains and their features according to the published literature. The second phase is a secondary analysis of qualitative data from 13 studies of interviews with 312 healthcare professionals on the perceived barriers and enablers to their application of research evidence in clinical practice. These data will be analyzed inductively using constant comparative analysis. For the third phase, we will conduct semi-structured interviews with key health system stakeholders and change agents to elicit their knowledge and beliefs about the contextual features that influence the effectiveness of implementation interventions and healthcare professionals’ use of evidence in clinical practice. Results from all three phases will be synthesized using a triangulation protocol to refine the context framework drawn from the concept analysis. The framework will then be assessed for content validity using an iterative Delphi approach with international experts (researchers and health system stakeholders/change agents). Discussion This research program will result in a framework that identifies the domains of context and their features that can facilitate or hinder: (1) healthcare professionals’ use of evidence in clinical practice and (2) the effectiveness of implementation interventions. The framework will increase the conceptual clarity of the term “context” for advancing implementation science, improving healthcare professionals’ use of evidence in clinical practice, and providing greater understanding of what interventions are likely to be effective in which contexts

Health risk behaviours among adolescents in the English-speaking Caribbean: a review

<p>Abstract</p> <p>Background</p> <p>The aim of this paper was to review and summarize research on prevalence of health risk behaviours, their outcomes as well as risk and protective factors among adolescents in the English-speaking Caribbean.</p> <p>Methods</p> <p>Searching of online databases and the World Wide Web as well as hand searching of the <it>West Indian Medical Journal </it>were conducted. Papers on research done on adolescents aged 10 – 19 years old and published during the period 1980 – 2005 were included.</p> <p>Results</p> <p>Ninety-five relevant papers were located. Five papers were published in the 1980s, 47 in the 1990s, and from 2000–2005, 43 papers. Health risk behaviours and outcomes were divided into seven themes. Prevalence data obtained for these, included lifetime prevalence of <b>substance use</b>: cigarettes-24% and marijuana-17%; <b>high risk sexual behaviour</b>: initiation of sexual activity ≤ 10 years old-19% and those having more than six partners-19%; <b>teenage pregnancy</b>: teens account for 15–20% of all pregnancies and one-fifth of these teens were in their second pregnancy; <b>Sexually-Transmitted Infections (STIs)</b>: population prevalence of gonorrhoea and/or chlamydia in 18–21 year-olds was 26%; <b>mental health</b>: severe depression in the adolescent age group was 9%, and attempted suicide-12%; <b>violence and juvenile delinquency</b>: carrying a weapon to school in the last 30 days-10% and almost always wanting to kill or injure someone-5%; <b>eating disorders and obesity</b>: overweight-11%, and obesity-7%. Many of the risk behaviours in adolescents were shown to be related to the adolescent's family of origin, home environment and parent-child relationships. Also, the protective effects of family and school connectedness as well as increased religiosity noted in studies from the United States were also applicable in the Caribbean.</p> <p>Conclusion</p> <p>There is a substantial body of literature on Caribbean adolescents documenting prevalence and correlates of health risk behaviours. Future research should emphasize the designing and testing of interventions to alleviate this burden.</p

Single cell RNA-seq reveals profound transcriptional similarity between Barrett's oesophagus and oesophageal submucosal glands

Barrett’s oesophagus is a precursor of oesophageal adenocarcinoma. In this common condition, squamous epithelium in the oesophagus is replaced by columnar epithelium in response to acid reflux. Barrett’s oesophagus is highly heterogeneous and its relationships to normal tissues are unclear. Here we investigate the cellular complexity of Barrett’s oesophagus and the upper gastrointestinal tract using RNA-sequencing of single cells from multiple biopsies from six patients with Barrett’s oesophagus and two patients without oesophageal pathology. We find that cell populations in Barrett’s oesophagus, marked by LEFTY1 and OLFM4, exhibit a profound transcriptional overlap with oesophageal submucosal gland cells, but not with gastric or duodenal cells. Additionally, SPINK4 and ITLN1 mark cells that precede morphologically identifiable goblet cells in colon and Barrett’s oesophagus, potentially aiding the identification of metaplasia. Our findings reveal striking transcriptional relationships between normal tissue populations and cells in a premalignant condition, with implications for clinical practice

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Additional file 28 of Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Additional file 28: Table S18. Sex-participation association of the variants with significant sex-specific lipid results

Additional file 17 of Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Additional file 17: Table S9. PheWAS UKB-MVP meta-analysis results for each index lipid variant at Bonferroni threshold for multiple testing