Racial Differences in the Distribution of Posterior Circulation Occlusive Disease

We Compared Clinical and Arteriographic Features in 27 White and 24 Black Patients with Symptomatic Posterior Circulation Occlusive Disease. the Degree of Arterial Stenosis Was Measured Independently by Two Examiners at 12 Sites within the Vertebrobasilar Territory. Racial Comparisons Were Made based Upon the Distribution of Extra- and Intracranial Occlusive Lesions and Symptomatic Sites of the Lesions. White Patients Had Significantly More Angina Pectoris, More Lesions of the Origin of the Left Vertebral Artery and More High-Grade Lesions of the Extracranial Vertebral Arteries. Black Patients Had Significantly Higher Mean Diastolic Blood Pressure, More Diabetes Mellitus, More Lesions of the Distal Basilar Artery, More High-Grade Lesions of Intracranial Branch Vessels and More Symptomatic Intracranial Branch Disease. Race Was Found to Be the Only Factor Increasing the Risk of Intracranial Posterior Circulation Occlusive Disease. Knowledge of the Contribution of Race to the Distribution of Posterior Circulation Lesions Will Help Guide Evaluation and Treatment Strategies for Patients with Vertebrobasilar Occlusive Disease. © 1985 American Heart Association, Inc

Inappropriate Drug Use and Risk of Transition to Nursing Homes Among Community-Dwelling Older Adults

Adverse events from inappropriate medications are preventable risk factors for nursing home admissions

Amount of Social Contact and Hip Fracture Mortality: SOCIAL CONTACT AND MORTALITY AFTER HIP FRACTURE

To study the association between amount of social contact and mortality after hip fracture in elderly participants

Workgroup Report: Biomonitoring Study Design, Interpretation, and Communication—Lessons Learned and Path Forward

Human biomonitoring investigations have provided data on a wide array of chemicals in blood and urine and in other tissues and fluids such as hair and human milk. These data have prompted questions such as a) What is the relationship between levels of environmental chemicals in humans and external exposures? b) What is the baseline or “background” level against which individual levels should be compared? and c) How can internal levels be used to draw conclusions about individual and/or population health? An interdisciplinary panel was convened for a 1-day workshop in November 2004 with the charge of focusing on three specific aspects of biomonitoring: characteristics of scientifically robust biomonitoring studies, interpretation of human biomonitoring data for potential risks to human health, and communication of results, uncertainties, and limitations of biomonitoring studies. In this report we describe the recommendations of the panel

Staphylococcus aureus Infections in US Veterans, Maryland, USA, 1999–20081

Trends in Staphylococcus aureus infections are not well described. To calculate incidence in overall S. aureus infection and invasive and noninvasive infections according to methicillin susceptibility and location, we conducted a 10-year population-based retrospective cohort study (1999–2008) using patient-level data in the Veterans Affairs Maryland Health Care System. We found 3,674 S. aureus infections: 2,816 (77%) were noninvasive; 2,256 (61%) were methicillin-resistant S. aureus (MRSA); 2,517 (69%) were community onset, and 1,157 (31%) were hospital onset. Sixty-one percent of noninvasive infections were skin and soft tissue infections; 1,112 (65%) of these were MRSA. Ten-year averaged incidence per 100,000 veterans was 749 (± 132 SD, range 549–954) overall, 178 (± 41 SD, range 114–259) invasive, and 571 (± 152 SD, range 364–801) noninvasive S. aureus infections. Incidence of all S. aureus infections significantly increased (p<0.001), driven by noninvasive, MRSA, and community-onset infections (p<0.001); incidence of invasive S. aureus infection significantly decreased (p<0.001)

Lowering of Circulating Sclerostin May Increase Risk of Atherosclerosis and Its Risk Factors: Evidence From a Genome-Wide Association Meta-Analysis Followed by Mendelian Randomization

OBJECTIVE: In this study, we aimed to establish the causal effects of lowering sclerostin, target of the antiosteoporosis drug romosozumab, on atherosclerosis and its risk factors. METHODS: A genome-wide association study meta-analysis was performed of circulating sclerostin levels in 33,961 European individuals. Mendelian randomization (MR) was used to predict the causal effects of sclerostin lowering on 15 atherosclerosis-related diseases and risk factors. RESULTS: We found that 18 conditionally independent variants were associated with circulating sclerostin. Of these, 1 cis signal in SOST and 3 trans signals in B4GALNT3, RIN3, and SERPINA1 regions showed directionally opposite signals for sclerostin levels and estimated bone mineral density. Variants with these 4 regions were selected as genetic instruments. MR using 5 correlated cis-SNPs suggested that lower sclerostin increased the risk of type 2 diabetes mellitus (DM) (odds ratio [OR] 1.32 [95% confidence interval (95% CI) 1.03-1.69]) and myocardial infarction (MI) (OR 1.35 [95% CI 1.01-1.79]); sclerostin lowering was also suggested to increase the extent of coronary artery calcification (CAC) (β = 0.24 [95% CI 0.02-0.45]). MR using both cis and trans instruments suggested that lower sclerostin increased hypertension risk (OR 1.09 [95% CI 1.04-1.15]), but otherwise had attenuated effects. CONCLUSION: This study provides genetic evidence to suggest that lower levels of sclerostin may increase the risk of hypertension, type 2 DM, MI, and the extent of CAC. Taken together, these findings underscore the requirement for strategies to mitigate potential adverse effects of romosozumab treatment on atherosclerosis and its related risk factors

Development and validation of a computerized expert system for evaluation of automated visual fields from the Ischemic Optic Neuropathy Decompression Trial

BACKGROUND: The objective of this report is to describe the methods used to develop and validate a computerized system to analyze Humphrey visual fields obtained from patients with non-arteritic anterior ischemic optic neuropathy (NAION) and enrolled in the Ischemic Optic Neuropathy Decompression Trial (IONDT). The IONDT was a multicenter study that included randomized and non-randomized patients with newly diagnosed NAION in the study eye. At baseline, randomized eyes had visual acuity of 20/64 or worse and non-randomized eyes had visual acuity of better than 20/64 or were associated with patients refusing randomization. Visual fields were measured before treatment using the Humphrey Field Analyzer with the 24-2 program, foveal threshold, and size III stimulus. METHODS: We used visual fields from 189 non-IONDT eyes with NAION to develop the computerized classification system. Six neuro-ophthalmologists ("expert panel") described definitions for visual field patterns defects using 19 visual fields representing a range of pattern defect types. The expert panel then used 120 visual fields, classified using these definitions, to refine the rules, generating revised definitions for 13 visual field pattern defects and 3 levels of severity. These definitions were incorporated into a rule-based computerized classification system run on Excel(® )software. The computerized classification system was used to categorize visual field defects for an additional 95 NAION visual fields, and the expert panel was asked to independently classify the new fields and subsequently whether they agreed with the computer classification. To account for test variability over time, we derived an adjustment factor from the pooled short term fluctuation. We examined change in defects with and without adjustment in visual fields of study participants who demonstrated a visual acuity decrease within 30 days of NAION onset (progressive NAION). RESULTS: Despite an agreed upon set of rules, there was not good agreement among the expert panel when their independent visual classifications were compared. A majority did concur with the computer classification for 91 of 95 visual fields. Remaining classification discrepancies could not be resolved without modifying existing definitions. Without using the adjustment factor, visual fields of 63.6% (14/22) patients with progressive NAION and no central defect, and all (7/7) patients with a paracentral defect, worsened within 30 days of NAION onset. After applying the adjustment factor, the visual fields of the same patients with no initial central defect and 5/7 of the patients with a paracentral defect were seen to worsen. CONCLUSION: The IONDT developed a rule-based computerized system that consistently defines pattern and severity of visual fields of NAION patients for use in a research setting

Genome-wide analysis identifies genetic effects on reproductive success and ongoing natural selection at the FADS locus

: Identifying genetic determinants of reproductive success may highlight mechanisms underlying fertility and identify alleles under present-day selection. Using data in 785,604 individuals of European ancestry, we identified 43 genomic loci associated with either number of children ever born (NEB) or childlessness. These loci span diverse aspects of reproductive biology, including puberty timing, age at first birth, sex hormone regulation, endometriosis and age at menopause. Missense variants in ARHGAP27 were associated with higher NEB but shorter reproductive lifespan, suggesting a trade-off at this locus between reproductive ageing and intensity. Other genes implicated by coding variants include PIK3IP1, ZFP82 and LRP4, and our results suggest a new role for the melanocortin 1 receptor (MC1R) in reproductive biology. As NEB is one component of evolutionary fitness, our identified associations indicate loci under present-day natural selection. Integration with data from historical selection scans highlighted an allele in the FADS1/2 gene locus that has been under selection for thousands of years and remains so today. Collectively, our findings demonstrate that a broad range of biological mechanisms contribute to reproductive success

Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney.

Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation