Marijuana Use and the Risk of Early Ischemic Stroke: The Stroke Prevention in Young Adults Study.

BACKGROUND AND PURPOSE: Few studies have examined the dose-response and temporal relationships between marijuana use and ischemic stroke while controlling for important confounders, including the amount of tobacco smoking. The purpose of our study was to address these knowledge gaps. METHODS: A population-based case-control study with 1090 cases and 1152 controls was used to investigate the relationship of marijuana use and early-onset ischemic stroke. Cases were first-ever ischemic stroke between the ages of 15 and 49 identified from 59 hospitals in the Baltimore-Washington region. Controls obtained by random digit dialing from the same geographic region were frequency-matched to cases by age, sex, region of residence and, except for the initial study phase, race. After excluding subjects with cocaine and other vasoactive substance use, the final study sample consisted of 751 cases and 813 controls. All participants underwent standardized interviews to characterize stroke risk factors and marijuana use. Unconditional logistic regression analysis was used to assess the relationships between marijuana use and risk of ischemic stroke, adjusting for age, sex, race, study phase, the amount of current tobacco smoking, current alcohol use, hypertension, and diabetes. RESULTS: After adjusting for other risk factors, including the amount of current tobacco smoking, marijuana use was not associated with ischemic stroke, regardless of the timing of use in relationship to the stroke, including ever use, use within 30 days, and use within 24 hours. There was a nonsignificant trend towards increased stroke risk among those who smoked marijuana at least once a week (odds ratio, 1.9 [95% CI, 0.8-4.9]). CONCLUSIONS: These analyses do not demonstrate an association between marijuana use and an increased risk of early-onset ischemic stroke, although statistical power was limited for assessing the association among very heavy users.

Using Typhoid Conjugate Vaccines to Prevent Disease, Promote Health Equity, and Counter Drug-Resistant Typhoid Fever.

Typhoid fever is a serious disease that disproportionately impacts children in low-resource settings in sub-Saharan Africa, South and Southeast Asia, and the Western Pacific. The prevalence of antimicrobial-resistant strains of S. Typhi continue to increase worldwide. Two safe, effective, and cost-effective typhoid conjugate vaccines (TCVs) are World Health Organization-prequalified for the prevention of typhoid fever in children as young as 6 months. Typhoid conjugate vaccines have proven effectiveness in preventing drug-resistant S. Typhi and have been deployed successfully in outbreak response and routine immunization scenarios. Broad and equitable distribution of TCVs is essential to combat the spread and potentially devastating consequences of typhoid fever. It is vital to empower decision-makers in typhoid-endemic countries to introduce TCVs and for leaders to embrace this critical tool to prevent typhoid fever, slow the spread of drug-resistant S. Typhi strains, promote health equity, and save lives.

Contribution of Common Genetic Variants to Risk of Early Onset Ischemic Stroke.

BACKGROUND AND OBJECTIVES: Current genome-wide association studies of ischemic stroke have focused primarily on late onset disease. As a complement to these studies, we sought to identifythe contribution of common genetic variants to risk of early onset ischemic stroke. METHODS: We performed a meta-analysis of genome-wide association studies of early onset stroke (EOS), ages 18-59, using individual level data or summary statistics in 16,730 cases and 599,237 non-stroke controls obtained across 48 different studies. We further compared effect sizes at associated loci between EOS and late onset stroke (LOS) and compared polygenic risk scores for venous thromboembolism between EOS and LOS. RESULTS: We observed genome-wide significant associations of EOS with two variants in ABO, a known stroke locus. These variants tag blood subgroups O1 and A1, and the effect sizes of both variants were significantly larger in EOS compared to LOS. The odds ratio (OR) for rs529565, tagging O1, 0.88 (95% CI: 0.85-0.91) in EOS vs 0.96 (95% CI: 0.92-1.00) in LOS, and the OR for rs635634, tagging A1, was 1.16 (1.11-1.21) for EOS vs 1.05 (0.99-1.11) in LOS; p-values for interaction = 0.001 and 0.005, respectively. Using polygenic risk scores, we observed that greater genetic risk for venous thromboembolism, another prothrombotic condition, was more strongly associated with EOS compared to LOS (p=0.008). DISCUSSION: The ABO locus, genetically predicted blood group A, and higher genetic propensity for venous thrombosis are more strongly associated with EOS than with LOS, supporting a stronger role of prothrombotic factors in EOS.

The copy number variation and stroke (CaNVAS) risk and outcome study.

BACKGROUND AND PURPOSE: The role of copy number variation (CNV) variation in stroke susceptibility and outcome has yet to be explored. The Copy Number Variation and Stroke (CaNVAS) Risk and Outcome study addresses this knowledge gap. METHODS: Over 24,500 well-phenotyped IS cases, including IS subtypes, and over 43,500 controls have been identified, all with readily available genotyping on GWAS and exome arrays, with case measures of stroke outcome. To evaluate CNV-associated stroke risk and stroke outcome it is planned to: 1) perform Risk Discovery using several analytic approaches to identify CNVs that are associated with the risk of IS and its subtypes, across the age-, sex- and ethnicity-spectrums; 2) perform Risk Replication and Extension to determine whether the identified stroke-associated CNVs replicate in other ethnically diverse datasets and use biomarker data (e.g. methylation, proteomic, RNA, miRNA, etc.) to evaluate how the identified CNVs exert their effects on stroke risk, and lastly; 3) perform outcome-based Replication and Extension analyses of recent findings demonstrating an inverse relationship between CNV burden and stroke outcome at 3 months (mRS), and then determine the key CNV drivers responsible for these associations using existing biomarker data. RESULTS: The results of an initial CNV evaluation of 50 samples from each participating dataset are presented demonstrating that the existing GWAS and exome chip data are excellent for the planned CNV analyses. Further, some samples will require additional considerations for analysis, however such samples can readily be identified, as demonstrated by a sample demonstrating clonal mosaicism. CONCLUSION: The CaNVAS study will cost-effectively leverage the numerous advantages of using existing case-control data sets, exploring the relationships between CNV and IS and its subtypes, and outcome at 3 months, in both men and women, in those of African and European-Caucasian descent, this, across the entire adult-age spectrum.