Cumulative anticholinergic exposure and white matter hyperintensity burden in community-dwelling older adults.

Background: Anticholinergic exposure is associated with dementia risk; however, the mechanisms for this association remain unclear. The objective of this study was to examine the association between anticholinergic exposure and white matter hyperintensity (WMH) burden.

Methods: This was a retrospective analysis of data from the Adult Changes in Thought (ACT) study, a prospective cohort study among adults aged ≥65 years on dementia risk factors.

A Community-Engaged Research Study to Inform Tailored Programming for Smoking Cessation and Lung Cancer Screening Among At-Risk LGBTQ+ Elders.

. Lung cancer is the leading cause of cancer death, with most cases attributable to cigarette smoking. Many communities within the lesbian, gay, bisexual, transgender and queer/questioning (LGBTQ+) umbrella have high rates of smoking, but focused lung cancer prevention is limited.

Managing Multiple Chronic Conditions during COVID-19 Among Patients with Social Health Risks.

Background: Optimal care for persons with multiple chronic conditions (MCC) requires primary and specialty care continuity, access to multiple providers, social risk assessment, and self-management support. The COVID-19 pandemic abruptly changed primary care delivery to increase reliance on telehealth and virtual care. We report on the experiences of individuals with MCC and their family caregivers on managing their health and receiving health care during the initial pandemic.

Integrated multimodal cell atlas of Alzheimer's disease.

Alzheimer's disease (AD) is the most common cause of dementia in older adults. Neuropathological and imaging studies have demonstrated a progressive and stereotyped accumulation of protein aggregates, but the underlying molecular and cellular mechanisms driving AD progression and vulnerable cell populations affected by disease remain coarsely understood. The current study harnesses single cell and spatial genomics tools and knowledge from the BRAIN Initiative Cell Census Network to understand the impact of disease progression on middle temporal gyrus cell types.

Associations between neighborhood built environment, residential property values, and adult BMI change: The Seattle Obesity Study III.

Objective: To examine associations between neighborhood built environment (BE) variables, residential property values, and longitudinal 1- and 2-year changes in body mass index (BMI).

Methods: The Seattle Obesity Study III was a prospective cohort study of adults with geocoded residential addresses, conducted in King, Pierce, and Yakima Counties in Washington State. Measured heights and weights were obtained at baseline (n = 879), year 1 (n = 727), and year 2 (n = 679).

Dashboard development for near real-time visualization of COVID-19 vaccine safety surveillance data in the vaccine safety datalink.

The Vaccine Safety Datalink (VSD) conducts active surveillance and vaccine safety research studies. Since the start of the U.S.

From the clinic to the community: Can health system data accurately estimate population obesity prevalence?

Objective: Health system data were assessed for how well they can estimate obesity prevalence in census tracts.

Methods: Clinical visit data were available from two large health systems (Kaiser Permanente Washington and University of Washington Medicine) in King County, Washington, as were census tract-level obesity prevalence estimates from the Behavioral Risk Factor Surveillance System (BRFSS). The health system data were geocoded to identify each patient's tract of residence, and the cross-sectional concordance between census tract-level obesity prevalence estimates computed from the two health systems in 2005 to 2006 and the concordance between University of Washington Medicine and BRFSS from 2012 to 2016 were assessed.

Characterizing patient assistance program use and patient responsiveness to specialty drug price for multiple sclerosis in a mid-size integrated health system.

There is concern that increasingly common use of patient assistance programs (PAPs), out-of-pocket assistance provided by manufacturers or foundations, distorts our understanding of patient behavior and insurance design incentives. Yet the current literature on prescription drug cost sharing largely overlooks their use. PAPs prevalence and impact on drug demand and price elasticity is a major knowledge gap.

A Mendelian randomization of γ' and total fibrinogen levels in relation to venous thromboembolism and ischemic stroke.

Fibrinogen is a key component of the coagulation cascade, and variation in its circulating levels may contribute to thrombotic diseases, such as venous thromboembolism (VTE) and ischemic stroke. Gamma prime (γ') fibrinogen is an isoform of fibrinogen that has anticoagulant properties. We applied 2-sample Mendelian randomization (MR) to estimate the causal effect of total circulating fibrinogen and its isoform, γ' fibrinogen, on risk of VTE and ischemic stroke subtypes using summary statistics from genome-wide association studies.

Mendelian Randomization Analysis of Hemostatic Factors and Their Contribution to Peripheral Artery Disease-Brief Report.

Background And Objective: Peripheral artery disease (PAD) is the third most common form of atherosclerotic vascular disease and is characterized by significant functional disability and increased cardiovascular mortality. Recent genetic data support a role for a procoagulation protein variant, the factor V Leiden mutation, in PAD. The role of other hemostatic factors in PAD remains unknown.

Genome-wide Modeling of Polygenic Risk Score in Colorectal Cancer Risk.

Accurate colorectal cancer (CRC) risk prediction models are critical for identifying individuals at low and high risk of developing CRC, as they can then be offered targeted screening and interventions to address their risks of developing disease (if they are in a high-risk group) and avoid unnecessary screening and interventions (if they are in a low-risk group). As it is likely that thousands of genetic variants contribute to CRC risk, it is clinically important to investigate whether these genetic variants can be used jointly for CRC risk prediction. In this paper, we derived and compared different approaches to generating predictive polygenic risk scores (PRS) from genome-wide association studies (GWASs) including 55,105 CRC-affected case subjects and 65,079 control subjects of European ancestry.

Soluble CD14 and Risk of Heart Failure and Its Subtypes in Older Adults.

Background: CD14 is a membrane glycoprotein primarily expressed by myeloid cells that plays a key role in inflammation. Soluble CD14 (sCD14) levels carry a poor prognosis in chronic heart failure (HF), but whether elevations in sCD14 precede HF is unknown. We tested the hypothesis that sCD14 is associated with HF incidence and its subtypes independent of major inflammatory biomarkers among older adults.

Primary Care Opioid Taper Plans Are Associated with Sustained Opioid Dose Reduction.

Background: Primary care providers prescribe most long-term opioid therapy and are increasingly asked to taper the opioid doses of these patients to safer levels. A recent systematic review suggests that multiple interventions may facilitate opioid taper, but many of these are not feasible within the usual primary care practice.

Objective: To determine if opioid taper plans documented by primary care providers in the electronic health record are associated with significant and sustained opioid dose reductions among patients on long-term opioid therapy.

Initiating Low-Value Inhaled Corticosteroids in an Inception Cohort with Chronic Obstructive Pulmonary Disease.

Decreasing medication overuse represents an opportunity to avoid harm and costs in the era of value-based purchasing. Studies of inhaled corticosteroids (ICS) overuse in chronic obstructive pulmonary disease (COPD) have examined prevalent use. Understanding initiation of low-value ICS among complex patients with COPD may help shape deadoption efforts.

Defining and Managing High-Priced Cures: Healthcare Payers' Opinions.

Objectives: Recent regulatory approvals of potentially curative but high-cost treatments have made these therapies a focus of health policy discussions. Cures present new challenges to healthcare payers because they have high upfront costs but have life-long health benefits. The objectives of this study are to understand how healthcare payers define and manage cures.

A large-scale exome array analysis of venous thromboembolism.

Although recent Genome-Wide Association Studies have identified novel associations for common variants, there has been no comprehensive exome-wide search for low-frequency variants that affect the risk of venous thromboembolism (VTE). We conducted a meta-analysis of 11 studies comprising 8,332 cases and 16,087 controls of European ancestry and 382 cases and 1,476 controls of African American ancestry genotyped with the Illumina HumanExome BeadChip. We used the seqMeta package in R to conduct single variant and gene-based rare variant tests.

A genome-wide association study identifies new loci for factor VII and implicates factor VII in ischemic stroke etiology.

Factor VII (FVII) is an important component of the coagulation cascade. Few genetic loci regulating FVII activity and/or levels have been discovered to date. We conducted a meta-analysis of 9 genome-wide association studies of plasma FVII levels (7 FVII activity and 2 FVII antigen) among 27 495 participants of European and African ancestry.

Do medical conditions predispose to the development of chronic back pain? A longitudinal co-twin control study of middle-aged males with 11-year follow-up.

Background: Poor general health predicts the transition to chronic back pain (CBP), but the role of specific medical conditions in the development of CBP is unclear. The study aim was to examine the association of medical conditions with the development of CBP ("incident CBP"), while controlling for familial factors, including genetics.

Methods: This was a longitudinal co-twin control study conducted in a nationwide United States sample from the Vietnam Era Twin Registry.

How can we get Iraq- and Afghanistan-deployed US Veterans to participate in health-related research? Findings from a national focus group study.

Background: Research participant recruitment is often fraught with obstacles. Poor response rates can reduce statistical power, threaten both internal and external validity, and increase study costs and duration. Military personnel are socialized to a specific set of laws, norms, traditions, and values; their willingness to participate in research may differ from civilians.

Pilot randomized trial of a telephone-delivered physical activity and weight management intervention for individuals with lower extremity amputation.

Background: Obesity and inactivity are common and burdensome for people with lower extremity amputation (LEA). The extent to which home-based physical activity/weight management programs are effective and safe for people with LEA is unknown. Translating effective interventions for understudied disability groups is needed.