Genetic correlates of phenotypic heterogeneity in autism

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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

Breast cancer diagnosis, patterns of care and burden of disease in Queensland, Australia (1998-2004): does being Indigenous make a difference?

ObjectivesWe compared patterns of care, comorbidity, disability-adjusted life-years (DALYs) and survival in Indigenous and non-Indigenous women with breast cancer in Queensland, Australia (1998–2004).MethodsA cohort study of Indigenous (n = 110) and non-Indigenous women (n = 105), frequency matched on age and remoteness. We used Pearson’s Chi-squared analysis to compare proportions, hazard models to assess survival differences and calculated disability-adjusted life years (DALYs).ResultsIndigenous women were more likely to be socially disadvantaged (43 vs. 20 %, p < 0.01) have comorbidity (42 vs. 18 % p < 0.01), and have regional spread or distant metastasis (metastasis, 51 vs. 36 %, p = 0.02) than non-Indigenous women; there was no difference in treatment patterns. More Indigenous women died in the follow-up period (p = 0.01). DALY’s were 469 and 665 per 100,000 for Indigenous and non-Indigenous women, respectively, with a larger proportion of the burden attributed to premature death among the former (63 vs. 59 %).ConclusionsIndigenous women with breast cancer received comparable treatment to their non-Indigenous counterparts. The higher proportion of DALYs related to early death in Indigenous women suggests higher fatality with breast cancer in this group. Later stage at diagnosis and higher comorbidity presence among Indigenous women reinforce the need for early detection and improved management of co-existing disease

Fluorinated lamellar phases: structural characterisation and use as templates for highly ordered silica materials

Highly ordered silica was synthesised by using a lamellar phase comprising the anionic fluorinated surfactant sodium perfluorooctanoate and the partially-fluorinated co-surfactant/oil 1H,1H,2H,2H-perfluorooctan-1-ol in water.</p

Collection and Reporting of Indigenous Status Information in Cancer Registries Around the World

PURPOSE Worldwide, Indigenous people often have disproportionally worse health and lower life expectancy than their non-Indigenous counterparts. Despite the impact of cancer on life expectancy, little is known about the burden of cancer for Indigenous people primarily because of the paucity of data. We investigated the collection and reporting of Indigenous status information among a global sample of population-based cancer registries (PBCRs). PARTICIPANTS AND METHODS An online survey was e-mailed to eligible registries using set inclusion criteria. Respondents were asked questions on the collection, reporting, and quality assessment of Indigenous status in their registers. RESULTS Eighty-three PBCRs from 25 countries were included. Of these, 66% reported that their registry collected Indigenous status data, although the quality of this variable had been assessed in less than half in terms of completeness (38%) and accuracy (47%). Two thirds of PBCRs who collected Indigenous status data (67%), from nine of 25 countries responded that cancer statistics for Indigenous people were reported using registry data. Key barriers to the collection of Indigenous status information included the lack of data collection at the point of care (79%), lack of transfer of Indigenous status to the cancer registry (46%), inadequate information systems (43%), and legislative limitations (32%). Important variations existed among world regions, although the lack of Indigenous status data collection at the point of care was commonly reported across all regions. CONCLUSION High-quality data collection is lacking for Indigenous peoples in many countries. To ensure the design and implementation of cancer control activities required to reduce disparities for Indigenous populations, health information systems, including cancer registries, need to be strengthened, and this must be done in dialogue with Indigenous leaders. </jats:sec