The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

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

School Nurses\u27 Perceptions of Concussion Management for Secondary School Student-Athletes

Background: School nurses play a vital role in concussion management at the secondary school level, often being the only on-site healthcare provider during school hours. However, little is known regarding how they perceive their role in the concussion management process. The purpose of this study was to explore school nurses’ perceptions and satisfaction with concussion management in the secondary school setting using a qualitative approach. Methods: Twenty-two school nurses employed within a United States secondary school setting completed individual, semi-structured phone interviews. Data were analyzed using a consensual qualitative research approach. Results: Four overall themes emerged. This manuscript focuses on one specific theme: school nurse perceptions and satisfaction regarding concussion management. Subthemes included: school nurses’ overall perception and satisfaction with current concussion management procedures, interactions with other involved personnel, concussion assessment tools, school nurses’ perceived role, current concussion management policies, concussion education, and school nurse continuing education specific to concussion. Conclusions: School nurses were generally positive regarding concussion management within their setting and were satisfied with their roles overall. However, participants identified a number of areas that require further attention to ensure an evidence-based, consistent team approach to concussion management to support best student outcomes and continuity of care

Medical Disqualification Following Concussion in Collegiate Student-Athletes: Findings from the CARE Consortium

The absence of evidence-based guidelines make medical disqualification (MDQ) following concussion one of the most challenging decision-making processes faced by sports medicine professionals. We aimed to compare premorbid and postmorbid factors between student-athletes that were and were not medically disqualified from sport following a concussion. Among 1832 student-athletes diagnosed with concussion within the CARE Consortium, 53 (2.9%) were medically disqualified (MDQ +) and 1779 (97.1%) were not medically disqualified (MDQ-). We used contingency tables and descriptive statistics for an initial evaluation of a broad list of premorbid and postmorbid factors. For those factors showing association with MDQ status, we calculated odds ratios and 95% confidence intervals for the odds of being MDQ + in the presence of the identified factor. History of 2 (OR: 3.2, 95% CI 1.5, 6.9) or 3 + (OR: 7.4, 95% CI 3.4, 15.9) previous concussions; 1 + headaches in past 3 months (OR: 1.8, 95% CI 1.0, 3.2); immediate removal from play (OR: 2.4, 95% CI 1.2, 4.9); alcohol (OR: 2.6, 95% CI 1.2, 5.4), tobacco (OR: 3.3, 95% CI 1.1, 9.5), or marijuana use since injury (OR: 5.4, 95% CI 1.5, 19.0); as well as prolonged recovery due to mental health alterations (OR: 5.3, 95% CI 2.0, 14.1) or motivation/malingering (OR: 7.5, 95% CI 3.3, 17.0) increased odds of being MDQ + . The MDQ + group took longer to become asymptomatic relative to the MDQ- group (MDQ + : 23.5 days, 95% CI 15.8, 31.2; MDQ-: 10.6 days, 95% CI 9.5, 11.6; p < 0.001). MDQ following concussion was relatively rare. We identified three patterns related to MDQ following concussion: (1) concussion and headache history were the only premorbid factors that differed (2) initial concussion presentation was more severe and more immediate in the MDQ + group, and (3) post-concussion recovery outcomes expressed the greatest differences between groups

Health-status outcomes with invasive or conservative care in coronary disease

BACKGROUND In the ISCHEMIA trial, an invasive strategy with angiographic assessment and revascularization did not reduce clinical events among patients with stable ischemic heart disease and moderate or severe ischemia. A secondary objective of the trial was to assess angina-related health status among these patients. METHODS We assessed angina-related symptoms, function, and quality of life with the Seattle Angina Questionnaire (SAQ) at randomization, at months 1.5, 3, and 6, and every 6 months thereafter in participants who had been randomly assigned to an invasive treatment strategy (2295 participants) or a conservative strategy (2322). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate differences between the treatment groups. The primary outcome of this health-status analysis was the SAQ summary score (scores range from 0 to 100, with higher scores indicating better health status). All analyses were performed in the overall population and according to baseline angina frequency. RESULTS At baseline, 35% of patients reported having no angina in the previous month. SAQ summary scores increased in both treatment groups, with increases at 3, 12, and 36 months that were 4.1 points (95% credible interval, 3.2 to 5.0), 4.2 points (95% credible interval, 3.3 to 5.1), and 2.9 points (95% credible interval, 2.2 to 3.7) higher with the invasive strategy than with the conservative strategy. Differences were larger among participants who had more frequent angina at baseline (8.5 vs. 0.1 points at 3 months and 5.3 vs. 1.2 points at 36 months among participants with daily or weekly angina as compared with no angina). CONCLUSIONS In the overall trial population with moderate or severe ischemia, which included 35% of participants without angina at baseline, patients randomly assigned to the invasive strategy had greater improvement in angina-related health status than those assigned to the conservative strategy. The modest mean differences favoring the invasive strategy in the overall group reflected minimal differences among asymptomatic patients and larger differences among patients who had had angina at baseline

Initial invasive or conservative strategy for stable coronary disease

BACKGROUND Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, 121.8 percentage points; 95% CI, 124.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used