12 research outputs found

    Cerebral small vessel disease genomics and its implications across the lifespan

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    White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.Peer reviewe

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

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    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

    Rose, Evie

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    Measuring the gaps in drinking water quality and policy across regional and remote Australia

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    Drinking water quality remains a persistent challenge across regional and remote Australia. We reviewed public reporting by 177 utilities and conducted a national assessment of reported exceedances against the health-based and aesthetic guideline values of the Australian Drinking Water Guidelines (ADWG). Four definitions of a basic level of drinking water quality were tested to quantify service gaps across regional and remote areas of each subnational jurisdiction in 2018–2019. At least 25,245 people across 99 locations with populations \u3c1000 reportedly accessed water services that did not comply with health-based guideline values. Including larger towns and water systems, the estimated service gap rises to at least 194,572 people across more than 115 locations. Considering health parameters and the ADWG definition of ‘good’ aesthetic characteristics, the reported service gap rises further to at least 627,736 people across 408 locations. Forty percent of all locations with recorded health exceedances were remote Indigenous communities. Monitoring and reporting gaps indicate that the actual incidence of non-compliance with the guideline values of the ADWG could be much higher than our estimates. Our results quantified the divergence in the assessment of water quality outcomes between Sustainable Development Goal Target 6.1 and the ADWG, demonstrated disparities between service levels in capital cities and the rest of Australia, and highlighted the need for place-based solutions. The methods and dataset provide a ‘proof-of-concept’ for an Australian national drinking water quality database to guide government investments in water services

    Measuring the gaps in drinking water quality and policy across regional and remote Australia

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    Abstract Drinking water quality remains a persistent challenge across regional and remote Australia. We reviewed public reporting by 177 utilities and conducted a national assessment of reported exceedances against the health-based and aesthetic guideline values of the Australian Drinking Water Guidelines (ADWG). Four definitions of a basic level of drinking water quality were tested to quantify service gaps across regional and remote areas of each subnational jurisdiction in 2018–2019. At least 25,245 people across 99 locations with populations <1000 reportedly accessed water services that did not comply with health-based guideline values. Including larger towns and water systems, the estimated service gap rises to at least 194,572 people across more than 115 locations. Considering health parameters and the ADWG definition of ‘good’ aesthetic characteristics, the reported service gap rises further to at least 627,736 people across 408 locations. Forty percent of all locations with recorded health exceedances were remote Indigenous communities. Monitoring and reporting gaps indicate that the actual incidence of non-compliance with the guideline values of the ADWG could be much higher than our estimates. Our results quantified the divergence in the assessment of water quality outcomes between Sustainable Development Goal Target 6.1 and the ADWG, demonstrated disparities between service levels in capital cities and the rest of Australia, and highlighted the need for place-based solutions. The methods and dataset provide a ‘proof-of-concept’ for an Australian national drinking water quality database to guide government investments in water services

    SPRIT

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    18th Annual Printing Education Week Celebrated January 14-19A PromiseActivities of RIT Sororities ReviewedAdvertise White Elephants In Spirit "Swap Column"An Open LetterBlock in School ElectsBloomfield-McCluneBook ReviewsBrand New IdeasBurlingame-FrisbyClark Union ClipsDorm DribblesDr. Ellingson Recently Elected Chamber of Commerce PresidentEagles Split; Trotters Take TwoEditor's MailEvening School Adds New CoursesFrat Sweetheart to be Selected at Valentine BallFun with FashionsLost RadianceMen's Bowling League Block A-1946Men's Bowling League-Block A 1945-1946Phi Upsilon Phi Holds Rush Party in Little BarnPrepare Chemistry TestRetailers Extend Vacation; Visit New York CityRetailers Waiting for TrainRings Displayed In Eastman BuildingS.K.D. Makes Selection from Entire SchoolSavage-HurwitzSweetheart BallotThumbnailsValue of College Training ExplainedWanted: Your Gripes, OpinionsWho?Wrestling to be on RIT Sports Panel Next Yea

    International consensus on a standard set of outcome measures for child and youth anxiety, depression, obsessive-compulsive disorder, and post-traumatic stress disorder

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    International audienceA major barrier to improving care effectiveness for mental health is a lack of consensus on outcomes measurement. The International Consortium for Health Outcomes Measurement (ICHOM) has already developed a consensus-based standard set of outcomes for anxiety and depression in adults (including the Patient Health Questionnaire-9, the Generalised Anxiety Disorder 7-item Scale, and the WHO Disability Schedule). This Position Paper reports on recommendations specifically for anxiety, depression, obsessive-compulsive disorder, and post-traumatic stress disorder in children and young people aged between 6 and 24 years. An international ICHOM working group of 27 clinical, research, and lived experience experts formed a consensus through teleconferences, an exercise using an adapted Delphi technique (a method for reaching group consensus), and iterative anonymous voting, supported by sequential research inputs. A systematic scoping review identified 70 possible outcomes and 107 relevant measurement instruments. Measures were appraised for their feasibility in routine practice (ie, brevity, free availability, validation in children and young people, and language translation) and psychometric performance (ie, validity, reliability, and sensitivity to change). The final standard set recommends tracking symptoms, suicidal thoughts and behaviour, and functioning as a minimum through seven primarily patient-reported outcome measures: the Revised Children's Anxiety and Depression Scale, the Obsessive Compulsive Inventory for Children, the Children's Revised Impact of Events Scale, the Columbia Suicide Severity Rating Scale, the KIDSCREEN-10, the Children's Global Assessment Scale, and the Child Anxiety Life Interference Scale. The set's recommendations were validated through a feedback survey involving 487 participants across 45 countries. The set should be used alongside the anxiety and depression standard set for adults with clinicians selecting age-appropriate measures

    Genetic Risk Score for Intracranial Aneurysms: Prediction of Subarachnoid Hemorrhage and Role in Clinical Heterogeneity

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    Background: Recently, common genetic risk factors for intracranial aneurysm (IA) and aneurysmal subarachnoid hemorrhage (ASAH) were found to explain a large amount of disease heritability and therefore have potential to be used for genetic risk prediction. We constructed a genetic risk score to (1) predict ASAH incidence and IA presence (combined set of unruptured IA and ASAH) and (2) assess its association with patient characteristics. Methods: A genetic risk score incorporating genetic association data for IA and 17 traits related to IA (so-called metaGRS) was created using 1161 IA cases and 407 392 controls from the UK Biobank population study. The metaGRS was validated in combination with risk factors blood pressure, sex, and smoking in 828 IA cases and 68 568 controls from the Nordic HUNT population study. Furthermore, we assessed association between the metaGRS and patient characteristics in a cohort of 5560 IA patients. Results: Per SD increase of metaGRS, the hazard ratio for ASAH incidence was 1.34 (95% CI, 1.20-1.51) and the odds ratio for IA presence 1.09 (95% CI, 1.01-1.18). Upon including the metaGRS on top of clinical risk factors, the concordance index to predict ASAH hazard increased from 0.63 (95% CI, 0.59-0.67) to 0.65 (95% CI, 0.62-0.69), while prediction of IA presence did not improve. The metaGRS was statistically significantly associated with age at ASAH (ÎČ=-4.82×10-3per year [95% CI, -6.49×10-3to -3.14×10-3]; P=1.82×10-8), and location of IA at the internal carotid artery (odds ratio=0.92 [95% CI, 0.86-0.98]; P=0.0041). Conclusions: The metaGRS was predictive of ASAH incidence, although with limited added value over clinical risk factors. The metaGRS was not predictive of IA presence. Therefore, we do not recommend using this metaGRS in daily clinical care. Genetic risk does partly explain the clinical heterogeneity of IA warranting prioritization of clinical heterogeneity in future genetic prediction studies of IA and ASAH
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