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URL: http://www.clinicaltrials.gov. Unique identifier: NCT02190500.

Pulmonary arterial hypertension (PAH) is a vascular disease characterized by persistent precapillary pulmonary hypertension (PH), leading to progressive right heart failure and premature death. The pathological mechanisms underlying this condition remain elusive. Analysis of global metabolomics from lung tissue of patients with PAH (n = 8) and control lung tissue (n = 8) leads to a better understanding of disease progression. Using a combination of high-throughput liquid-and-gas-chromatography-based mass spectrometry, we showed unbiased metabolomic profiles of disrupted arginine pathways with increased Nitric oxide (NO) and decreased arginine. Our results also showed specific metabolic pathways and genetic profiles with increased Sphingosine-1-phosphate (S1P) metabolites as well as increased Heme metabolites with altered oxidative pathways in the advanced stage of the human PAH lung. The results suggest that PAH has specific metabolic pathways contributing to the vascular remodeling in severe pulmonary hypertension. Profiling metabolomic alterations of the PAH lung has provided a new understanding of the pathogenic mechanisms of PAH, which benefits therapeutic targeting to specific metabolic pathways involved in the progression of PAH.

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Propensity score-based analysis is increasingly being used in observational studies to estimate the effects of treatments, interventions, and exposures. We introduce the concept of the propensity score and how it can be used in observational research. We describe four different ways of using the propensity score: matching on the propensity score, inverse probability of treatment weighting using the propensity score, stratification on the propensity score, and covariate adjustment on the propensity score (with a focus on the first two). We provide recommendations for the use and reporting of propensity score methods for the conduct of observational studies in neurological research.

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Background Loneliness is common in older adults, and it is associated with unhealthy behaviours, including substance use. We evaluated the association between loneliness and self-reported use of opioids and benzodiazepines in older adults. Methods We used data from the Canadian Community Health Survey’s ‘Healthy Aging’ sub-survey and included adults 65 years or older who administered their own medications. We classified individuals as lonely if they scored 6 or more on the three -item University of California, Los Angeles’s Loneliness Scale. We used multinomial logistic regression models, adjusting for demographics and self-reported comorbidities, to describe the association between loneliness and daily or occasional use of opioids, benzodiazepines and non-opioid analgesics. We also explored the association between loneliness and polypharmacy. Results Our cohort included 15,302 older adults, of whom 2,096 (13.7%) were classified as lonely. Daily use of opioids (4.1%) and benzodiazepines (1.7%) were less common than daily use of non-opioid analgesics (33.9%). Lonely older adults had higher daily use of opioids (odds ratio [OR] 1.61, 1.31-1.98) and benzodiazepines (OR 1.66, 1.21-2.28), but not non-opioid analgesics (OR 1.05, 0.92-1.19). Loneliness was not associated with occasional use of opioids, benzodiazepines or non-opioid analgesics in older adults, but was associated with polypharmacy (OR 1.27, 1.06-1.52). Conclusions Loneliness in older adults is associated with increased daily use of opioids and benzodiazepines. Further research should evaluate patient- and physician-level factors that mediate this association, and develop strategies to mitigate loneliness and its attendant adverse outcomes.

Background It is not known if initial reductions in hospitalization for stroke and myocardial infarction early during the coronavirus disease–2019 pandemic were followed by subsequent increases. We describe the rates of emergency department visits for stroke and myocardial infarction through the pandemic phases. Methods We used linked administrative data to compare the weekly age- and sex-standardized rates of visits for stroke and myocardial infarction in Ontario, Canada in the first 9 months of 2020 to the mean baseline rates (2015-2019) using rate ratios (RRs) and 95% confidence intervals (CIs). We compared care and outcomes by pandemic phases (pre-pandemic was January-March, lockdown was March-May, early reopening was May-July, and late reopening was July-September). Results We identified 15,682 visits in 2020 for ischemic stroke (59.2%; n = 9279), intracerebral hemorrhage (12.2%; n = 1912), or myocardial infarction (28.6%; n = 4491). The weekly rates for stroke visits in 2020 were lower during the lockdown and early reopening than at baseline (RR 0.76, 95% CI [0.66, 0.87] for the largest weekly decrease). The weekly rates for myocardial infarction visits were lower during the lockdown only (RR 0.61, 95% CI [0.46, 0.77] for the largest weekly decrease), and there was a compensatory increase in visits following reopening. Ischemic stroke 30-day mortality was increased during the lockdown phase (11.5% pre-coronavirus disease; 12.2% during lockdown; 9.2% during early reopening; and 10.6% during late reopening, P = 0.015). Conclusion After an initial reduction in visits for stroke and myocardial infarction, there was a compensatory increase in visits for myocardial infarction. The death rate after ischemic stroke was higher during the lockdown than in other phases.