Search

Background: In randomized clinical trials, treatment effects may vary, and this possibility is referred to as heterogeneity of treatment effect (HTE). One way to quantify HTE is to partition participants into subgroups based on individual's risk of experiencing an outcome, then measuring treatment effect by subgroup. Given the limited availability of externally validated outcome risk prediction models, internal models (created using the same dataset in which heterogeneity of treatment analyses also will be performed) are commonly developed for subgroup identification. We aim to compare different methods for generating internally developed outcome risk prediction models for subject partitioning in HTE analysis. Methods: Three approaches were selected for generating subgroups for the 2,441 participants from the United States enrolled in the ASPirin in Reducing Events in the Elderly (ASPREE) randomized controlled trial. An extant proportional hazards-based outcomes predictive risk model developed on the overall ASPREE cohort of 19,114 participants was identified and was used to partition United States' participants by risk of experiencing a composite outcome of death, dementia, or persistent physical disability. Next, two supervised non-parametric machine learning outcome classifiers, decision trees and random forests, were used to develop multivariable risk prediction models and partition participants into subgroups with varied risks of experiencing the composite outcome. Then, we assessed how the partitioning from the proportional hazard model compared to those generated by the machine learning models in an HTE analysis of the 5-year absolute risk reduction (ARR) and hazard ratio for aspirin vs. placebo in each subgroup. Cochran's Q test was used to detect if ARR varied significantly by subgroup. Results: The proportional hazard model was used to generate 5 subgroups using the quintiles of the estimated risk scores; the decision tree model was used to generate 6 subgroups (6 automatically determined tree leaves); and the random forest model was used to generate 5 subgroups using the quintiles of the prediction probability as risk scores. Using the semi-parametric proportional hazards model, the ARR at 5 years was 15.1% (95% CI 4.0–26.3%) for participants with the highest 20% of predicted risk. Using the random forest model, the ARR at 5 years was 13.7% (95% CI 3.1–24.4%) for participants with the highest 20% of predicted risk. The highest outcome risk group in the decision tree model also exhibited a risk reduction, but the confidence interval was wider (5-year ARR = 17.0%, 95% CI= -5.4–39.4%). Cochran's Q test indicated ARR varied significantly only by subgroups created using the proportional hazards model. The hazard ratio for aspirin vs. placebo therapy did not significantly vary by subgroup in any of the models. The highest risk groups for the proportional hazards model and random forest model contained 230 participants each, while the highest risk group in the decision tree model contained 41 participants. Conclusions: The choice of technique for internally developed models for outcome risk subgroups influences HTE analyses. The rationale for the use of a particular subgroup determination model in HTE analyses needs to be explicitly defined based on desired levels of explainability (with features importance), uncertainty of prediction, chances of overfitting, and assumptions regarding the underlying data structure. Replication of these analyses using data from other mid-size clinical trials may help to establish guidance for selecting an outcomes risk prediction modelling technique for HTE analyses. [ABSTRACT FROM AUTHOR]

Background: This study examined the associations of body mass index (BMI) and waist circumference (WC), as well as their short‐ and long‐term changes over time, with incident dementia in older individuals. Methods: Data came from 18,837 community‐dwelling individuals aged 65+ years from Australia and the United States, who were relatively healthy without major cognitive impairment at enrolment. Anthropometric measures were prospectively assessed at baseline, as well as change and variability from baseline to year two (three time‐points). In a subgroup (n = 11,176), self‐reported weight at age 18 and 70+ years was investigated. Dementia cases satisfied DSM‐IV criteria. Cox regression was used to examine the associations between anthropometric measures and incident risk of dementia. Results: Compared to normal weight, an overweight (HR: 0.67, 95%CI: 0.57–0.79, p < 0.001) or obese BMI (HR: 0.73, 95%CI: 0.60–0.89, p = 0.002), or a larger WC (elevated, HR: 0.71, 95%CI: 0.58–0.86, p < 0.001; highly elevated, HR: 0.65, 95%CI: 0.55–0.78, p < 0.001; relative to low) at baseline was associated with lower dementia risk. In contrast, substantial increases in BMI (>5%) over 2 years after baseline were associated with higher dementia risk (HR: 1.49, 95% CI: 1.17–1.91, p = 0.001). Increased dementia risk was also seen with an underweight BMI at baseline and a 2‐year BMI decrease (>5%), but these associations appeared only in the first 4 years of follow‐up. Compared to normal weight at both age 18 and 70+ years, being obese at both times was associated with increased dementia risk (HR: 2.27, 95%CI: 1.22–4.24, p = 0.01), while obesity only at age 70+ years was associated with decreased risk (HR: 0.70, 95%CI: 0.51–0.95, p = 0.02). Conclusions: Our findings suggest that long‐term obesity and weight gain in later life may be risk factors for dementia. Being underweight or having substantial weight loss in old age may be early markers of pre‐clinical dementia. [ABSTRACT FROM AUTHOR]

Background: Surrogates and physicians may differ in their priorities and perspectives when making decisions for incapacitated, critically ill patients. Objectives: To determine the extent to which surrogate and physician decisions to sustain life support are associated with their expectations for patient outcomes. Setting/Subjects: Surrogates and physicians of 100 mechanically ventilated patients at an academic, tertiary care medical center in the United States were surveyed. Measurements: Linear regression was used to determine if participant expectations for patient survival, good quality of life, and confidence in these expectations were associated with their agreement that mechanical ventilation should be continued if required for patient survival. Results: Surrogates were more likely than physicians to expect that patients would be alive in three months (91% interquartile range [IQR 70–95%] vs. 65% [IQR 43–77%], p < 0.001) and have good quality of life in three months (71% [IQR 50–90%] vs. 40% [IQR 19–50%], p < 0.001). Surrogates who were most confident in their prognostic abilities were also the most optimistic for good patient outcomes. As such, expectations for patient survival and good quality of life were not associated with level agreement that mechanical ventilation should be continued among confident surrogates, (R2 = 0.03, p = 0.13) and (R2 = 0.01, p = 0.53), respectively. In contrast, among physicians, confidence was not synonymous with optimism. Instead, the significant associations between expectations for patient survival and good quality of life with the agreement that mechanical ventilation should be continued were strengthened when physicians were confident, (R2 = 0.34, p < 0.01) and (R2 = 0.47, p < 0.001), respectively. Conclusion: Surrogates and physicians have different approaches to incorporating their expectations for patient prognosis and their confidence in these expectations when they are making decisions for incapacitated critically ill patients. [ABSTRACT FROM AUTHOR]

Frailty is a state of heightened vulnerability and susceptibility to physiologic stressors that increases with age. It has shown increasing utility in predicting a range of adverse health outcomes. Here, we characterize a 67-item deficit-accumulation frailty index (FI) in 19 110 community-dwelling individuals in the ASPirin in Reducing Events in the Elderly clinical trial. Participants aged 65-98 years were recruited from the United States and Australia and were without diagnosed dementia and cardiovascular disease, and major physical disability. The median FI score was .10 (interquartile range: .07-.14) at baseline, and the prevalence of frailty (FI > .21) increased from 8.1% to 17.4% after 6 years. FI was positively associated with age, and women had significantly higher scores than men at all ages. The FI was negatively correlated with gait speed (r = -.31) and grip strength (r = -.46), and strongly associated with a modified Fried's frailty phenotype (p < .0001, for all comparisons). Frailty was associated with the primary composite outcome capturing independent life lived free of major disability and dementia, and increased the rate of persistent physical disability (hazard ratio: 21.3, 95% confidence interval: 15.6-28.9). It added significantly to the predictive capacity of these outcomes above age, sex, and ethnicity alone. The FI is thus a useful biomarker of aging even among relatively healthy older individuals and provides important information about an individual's vulnerability to and risk of disease. [ABSTRACT FROM AUTHOR]

Background: Cerebrovascular events, dementia, and cancer can contribute to physical disability with activities of daily living (ADL). It is unclear whether low-dose aspirin reduces this burden in aging populations. In a secondary analysis, we now examine aspirin's effects on incident and persistent ADL disability within a primary prevention aspirin trial in community-dwelling older adults.Methods: The ASPREE (ASPirin in Reducing Events in the Elderly) trial of daily 100 mg aspirin versus placebo recruited 19 114 healthy adults aged 70+ years (65+ years if U.S. minority) in Australia and the United States. Six basic ADLs were assessed every 6 months. Incident ADL disability was defined as inability or severe difficulty with ≥1 ADL; persistence was confirmed if the same ADL disability remained after 6 months. Proportional hazards modeling compared time to incident or persistent ADL disability for aspirin versus placebo; death without prior disability was a competing risk.Results: Over a median of 4.7 years, incident ADL disability was similar in those receiving aspirin (776/9525) and placebo (787/9589) with walking, bathing, dressing, and transferring the most commonly reported. Only 24% of incident ADL disability progressed to persistent. Persistent ADL disability was lower in the aspirin group (4.3 vs 5.3 events/1000 py; hazard ratio [HR] = 0.81, 95% confidence interval [CI]: 0.66-1.00), with bathing and dressing the most common ADL disabilities in both groups. Following persistent ADL disability, there were more deaths in the aspirin group (24 vs 12).Discussion: Low-dose aspirin in initially healthy older people did not reduce the risk of incident ADL disability, although there was evidence of reduced persistent ADL disability. [ABSTRACT FROM AUTHOR]

Background: ASPirin in Reducing Events in the Elderly, a randomized, double-blind, placebo-controlled trial of daily low-dose aspirin (100 mg) in older adults, showed an increase in all-cause mortality, primarily due to cancer. In contrast, prior randomized controlled trials, mainly involving younger individuals, demonstrated a delayed cancer benefit with aspirin. We now report a detailed analysis of cancer incidence and mortality.Methods: 19 114 Australian and US community-dwelling participants aged 70 years and older (US minorities 65 years and older) without cardiovascular disease, dementia, or physical disability were randomly assigned and followed for a median of 4.7 years. Fatal and nonfatal cancer events, a prespecified secondary endpoint, were adjudicated based on clinical records.Results: 981 cancer events occurred in the aspirin and 952 in the placebo groups. There was no statistically significant difference between groups for all incident cancers (hazard ratio [HR] = 1.04, 95% confidence interval [CI] = 0.95 to 1.14), hematological cancer (HR = 0.98, 95% CI = 0.73 to 1.30), or all solid cancers (HR = 1.05, 95% CI = 0.95 to 1.15), including by specific tumor type. However, aspirin was associated with an increased risk of incident cancer that had metastasized (HR = 1.19, 95% CI = 1.00 to 1.43) or was stage 4 at diagnosis (HR = 1.22, 95% CI = 1.02 to 1.45), and with higher risk of death for cancers that presented at stages 3 (HR = 2.11, 95% CI = 1.03 to 4.33) or 4 (HR = 1.31, 95% CI = 1.04 to 1.64).Conclusions: In older adults, aspirin treatment had an adverse effect on later stages of cancer evolution. These findings suggest that in older persons, aspirin may accelerate the progression of cancer and, thus, suggest caution with its use in this age group. [ABSTRACT FROM AUTHOR]

Importance: Depression is associated with increased inflammation, which may precede its onset, especially in older people. Some preclinical data suggest potential antidepressant effects of aspirin, supported by limited observational data suggesting lower rates of depression in individuals treated with aspirin. There currently appears to be no evidence-based pharmacotherapies for the primary prevention of depression.Objective: To determine whether low-dose aspirin (100 mg) reduces the risk of depression in healthy older adults.Design, Setting, and Participants: This double-blinded, placebo-controlled randomized clinical trial was a substudy of the Aspirin in Reducing Events in the Elderly (ASPREE) trial, which examined if aspirin increased healthy life span, defined as survival free of dementia and disability. The prespecified secondary outcome was depression. Individuals of all races/ethnicities older than 70 years in Australia, as well as white individuals older than 70 years and black and Hispanic individuals older than 65 years in the United States, were included.Interventions: Participants were randomized to aspirin (100 mg daily) or placebo, with a median (interquartile range) follow-up of 4.7 (3.5-5.6) years.Main Outcomes and Measures: The primary outcome was a proxy measure of major depressive disorder defined as a score of 8 or more on the Center for Epidemiologic Studies Depression 10-item (CES-D-10) scale.Results: Of the 19 114 participants enrolled in the trial, 9525 received aspirin and 9589 received a placebo. The mean (SD) age was 75.2 (4.0) years in the aspirin group and 75.1 (4.5) years in the placebo group; 9531 (56.4%) were women. Participants' demographics and clinical characteristics at baseline were similar between groups. A total of 79 886 annual CES-D-10 measurements were taken, with a mean of 4.2 measurements per participant. There were no significant differences at annual visits in the proportions of CES-D-10 scores of 8 or more between the aspirin and placebo groups. The incidence rate of new CES-D-10 scores of 8 or more was 70.4 events per 1000 person-years in the aspirin group and 69.1 in the placebo group (hazard ratio, 1.02 [95% CI, 0.96-1.08]; P = .54).Conclusions and Relevance: Low-dose aspirin did not prevent depression in this large-scale study of otherwise healthy older adults.Trial Registration: ClinicalTrials.gov Identifier: NCT01038583. [ABSTRACT FROM AUTHOR]

Background: A small number of older adults in the United States who agree to brain donation for clinical research belong to diverse racial, ethnic, and economic groups. Those who agree, however, are less likely to have completed brain autopsies compared with older non-Latino Whites of higher socioeconomic status. As such, our understanding of Alzheimer's disease and related dementias remains limited in these underrepresented and understudied populations. Here, we examine perceived impediments to completed brain autopsies among diverse older adults who have agreed to brain donation for clinical research.Methods: Participants (N=22) were older adults (mean age=77 years) who self-identified as African American (n=8), Latino (n=6), or White of lower income (n=8). All participants had previously agreed to brain donation via the Uniform Anatomical Gift Act. Each participant took part in a one-time, semi-structured focus group. Data were analyzed using a Grounded Theory Approach with both Open Coding and Constant Comparative Coding.Results: Perceived impediments to completed brain autopsies varied by group. Older African Americans and older Latinos expressed concern about a lack of follow-through by family members regarding their brain donation wishes. Older Whites of lower income indicated that their own uncertainty surrounding the processes of brain donation and brain autopsy might serve as an impediment.Discussion: Diverse older adults expressed different perceived impediments to having brain autopsies completed upon their death. Continuous education for diverse older adults and their family members regarding brain donation for clinical research, including clear guidelines and processes, may facilitate completed brain autopsies among diverse older adults. [ABSTRACT FROM AUTHOR]

BACKGROUND Despite readily available treatments, control of blood pressure (BP) with population aging remains suboptimal. Further, there are gaps in the understanding of the management of high BP in the aged. We explored antihypertensive treatment and control among elderly hypertensive participants free from overt cardiovascular disease (CVD), and identified factors related to both "untreated" and "treated but uncontrolled" high BP. METHODS We analyzed baseline data from 19,114 individuals aged ≥65 years enrolled from Australia and United States (US) in the ASPirin in Reducing Events in the Elderly study. Hypertension was defined as an average systolic/diastolic BP ≥140/90 mm Hg and/or the use of any BP lowering medication. "Controlled hypertension" was defined if participants were receiving antihypertensive medication and BP <140 and 90 mm Hg. Descriptive analyses were used to summarize hypertension control rates; logistic regression was used to investigate relationships with treatment and BP control. RESULTS Overall, 74% (14,213/19,114) of participants were hypertensive; and of these 29% (4,151/14,213) were untreated. Among those treated participants, 53% (5,330/10,062) had BP ≥140/90 mm Hg. Participants who were untreated were more likely to be men, have higher educational status, and be in good physical health, and less likely to have significant comorbidities. The factors related to "treated but uncontrolled" BP included older age, male, Black race (vs. White), using antihypertensive monotherapy (vs. multiple) and residing in Australia (vs. US). CONCLUSIONS High levels of "untreated" and "treated but uncontrolled" BP occur in healthy elderly people without CVD, suggesting there are opportunities for better BP control in the primary prevention of CVD in this population. CLINICAL TRIALS REGISTRATION NCT01038583. [ABSTRACT FROM AUTHOR]

Objective: This study was conducted to estimate prevalence rates and factors associated with depressive symptoms indexed by the Centre for Epidemiological Studies-Depression (CES-D-10) score in a large sample of community-dwelling healthy older adults from Australia and the United States. Convergent and divergent validity of the CES-D-10 were also examined.Methods: A total of 19 114 individuals aged greater than or equal to 65 years old were enrolled from a primary prevention clinical trial. Depressive symptoms were classified using the CES-D-10 score greater than or equal to 8 and greater than or equal to 10. Gender-specific prevalence for subgroups according to sociodemographic characteristics were reported, and factors associated with depressive symptoms were estimated.Results: The overall prevalence rates of depressive symptoms were 9.8%, 95% CI, 8.5-11.2 and 5.0%, 95% CI, 4.0-6.0, according to the CES-D-10 score greater than or equal to 8 and greater than or equal to 10, respectively. Depressive symptoms were more common in women, individuals with less than 12 years of education, those living alone or in a residential care, ethnic minorities, current smokers, and former alcohol users. Convergent and divergent validities of the CES-D-10 were confirmed by observing strong negative association with the SF-12 mental health component and a modest negative association with SF-12 physical component, respectively.Conclusions: This study reports the prevalence of depressive symptoms in Australian and US community-dwelling healthy older populations. These findings emphasize the high burden of the condition and factors associated with depressive symptoms, to better inform clinicians and help with early detection and treatment of depression in this age group. [ABSTRACT FROM AUTHOR]

Objective: To present normative performance data on the Modified Mini-Mental State (3MS) examination for healthy community-dwelling older individuals according to gender, age, education level, and ethno-racial group. Method: More than 19,000 generally healthy older men and women without a diagnosis of dementia were recruited from the general population in Australia and the U.S. for the ASPirin in Reducing Events in the Elderly (ASPREE) study. The 3MS exam was administered as part of the baseline screening and individuals scoring above 77 were eligible to participate. Results: The sample comprised 16,360 Australian whites, 1080 U.S. whites, 895 African-Americans and 316 Hispanic/Latinos. The median age of participants was 74 years (range 65–98), with an average of 12 years of education and 56% were female. Increasing age and fewer years of completed education were associated with lower scores on the 3MS. Women scored higher than men in most age and education categories. Differences across ethno-racial groups were found. With factor analysis, four factors were identified which accounted for 35% of the between-person variance in 3MS scores for white Australians. Conclusions: This large cohort of older individuals provides some of the most comprehensive 3MS normative data to be generated for whites (Australian and U.S.), Hispanic/Latinos and African-Americans, by age, gender, and educational attainment. These findings will serve as important reference standards for monitoring cognitive function in generally healthy older individuals, becoming increasingly important as this fraction of the population increases. [ABSTRACT FROM AUTHOR]

Purpose: To explore the relationship between sociodemographic and lifestyle variables with health-related quality of life (HRQoL) of a large cohort of 'healthy' older individuals.Methods: The sample included individuals aged 65+ years from Australia (N = 16,703) and the USA (N = 2411) enrolled in the ASPirin in Reducing Events in the Elderly (ASPREE) multicentre placebo-controlled trial study and free of cardiovascular disease, dementia, serious physical disabilities or 'fatal' illnesses. The associations with the physical (PCS) and mental component scores (MCS) of HRQoL (SF-12 questionnaire) were explored using multiple linear regression models from data collected at baseline (2010-2014).Results: The adjusted PCS mean was slightly higher in the USA (49.5 ± 9.1) than Australia (48.2 ± 11.6; p < 0.001), but MCS was similar in both samples (55.7 ± 7.5 and 55.7 ± 9.6, respectively; p = 0.603). Males, younger participants, better educated, more active individuals, or those currently drinking 1-2 alcoholic drinks/day showed a better HRQoL (results more evident for PCS than MCS), while current heavy smokers had the lowest physical HRQoL in both countries. Neither age, walking time, nor alcohol intake was associated with MCS in either cohort.Conclusions: Baseline HRQoL of ASPREE participants was higher than that reported in population-based studies of older individuals, but the associations between sociodemographic and lifestyle variables were consistent with the published literature. As the cohort ages and develops chronic diseases, ASPREE will be able to document HRQoL changes. [ABSTRACT FROM AUTHOR]

Background: There are no primary prevention trials of aspirin with relevant geriatric outcomes in elderly people. ASPirin in Reducing Events in the Elderly (ASPREE) is a placebo-controlled trial of low-dose aspirin that will determine whether 5 years of daily 100-mg enteric-coated aspirin extends disability-free and dementia-free life in a healthy elderly population and whether these benefits outweigh the risks.Methods: Set in primary care, this randomized double-blind placebo-controlled trial has a composite primary endpoint of death, incident dementia or persistent physical disability. Participants aged 70+ years (non-minorities) or 65+ years (U.S. minorities) were free of cardiovascular disease, dementia, or physical disability and without a contraindication to, or indication for, aspirin. Baseline data include physical and lifestyle, personal and family medical history, hemoglobin, fasting glucose, creatinine, lipid panel, urinary albumin:creatinine ratio, cognition (3MS, HVLT-R, COWAT, SDMT), mood (CES-D-10), physical function (gait speed, grip strength), Katz activities of daily living and quality of life (SF-12).Results: Recruitment ended in December 2014 with 16,703 Australian and 2,411 U.S. participants, a median age of 74 (range 65-98) years and 56% women. Approximately 55% of the U.S. cohort were from minority groups; 9% of the total cohort. Proportions with hypertension, overweight, and chronic kidney disease were similar to age-matched populations from both countries although lower percentages had diabetes, dyslipidemia, and osteoarthritis.Discussion: Findings from ASPREE will be generalizable to a healthier older population in both countries and will assess whether the broad benefits of daily low-dose aspirin in prolonging independent life outweigh the risks. [ABSTRACT FROM AUTHOR]

The article highlights the challenges between technologies advancing large scale health data sharing and health data privacy and security in the U.S. Topics discussed include precision medicine and population health research in health care industry; laws defined by the U.S. Food and Drug Administration; provisions of the Health Insurance Portability and Accountability Act; and advances in addition to mobile technologies and patient partnerships.

The author reflects on the various innovations and invention related with improvement of health system in the U.S. with reference to David E Barmes Global Health Lecture given by the author at the National Institutes of Health in Bethesda on February 15, 2011. He discusses the benefits of the U.S. President, Barack Obama's Global Health Initiative (GHI) program which aims at providing higher vaccine availability at low price, life-saving care for infants and HIV infection prevention.

Introduction: There is limited evidence about factors related to the timeliness of dementia diagnosis in healthcare settings., Methods: In five prospective cohorts at Rush Alzheimer's Disease Center, we identified participants with incident dementia based on annual assessments and examined the timing of healthcare diagnoses in Medicare claims. We assessed sociodemographic, health, and psychosocial correlates of timely diagnosis., Results: Of 710 participants, 385 (or 54%) received a timely claims diagnosis within 3 years prior to or 1 year following dementia onset. In logistic regressions accounting for demographics, we found Black participants (odds ratio [OR] = 2.15, 95% confidence interval [CI]: 1.21 to 3.82) and those with better cognition at dementia onset (OR = 1.48, 95% CI: 1.10 to 1.98) were at higher odds of experiencing a diagnostic delay, whereas participants with higher income (OR = 0.89, 95% CI: 0.81 to 0.97) and more comorbidities (OR = 0.94, 95% CI: 0.89 to 0.98) had lower odds., Discussion: We identified characteristics of individuals who may miss the optimal window for dementia treatment and support., Highlights: We compared the timing of healthcare diagnosis relative to the timing of incident dementia based on rigorous annual evaluation. Older Black adults with lower income, higher cognitive function, and fewer comorbidities were less likely to be diagnosed in a timely manner by the healthcare system., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Importance: Black or African American (hereinafter, Black) and Hispanic or Latino/a/x (hereinafter, Latinx) adults are disproportionally affected by Alzheimer disease, but most research studies do not enroll adequate numbers of both of these populations. The Alzheimer's Disease Neuroimaging Initiative-3 (ADNI3) launched a diversity taskforce to pilot a multipronged effort to increase the study inclusion of Black and Latinx older adults., Objective: To describe and evaluate the culturally informed and community-engaged inclusion efforts to increase the screening and enrollment of Black and Latinx older adults in ADNI3., Design, Setting, and Participants: This cross-sectional study used baseline data from a longitudinal, multisite, observational study conducted from January 15, 2021, to July 12, 2022, with no follow-up. The study was conducted at 13 ADNI3 sites in the US. Participants included individuals aged 55 to 90 years without cognitive impairment and those with mild cognitive impairment or Alzheimer disease., Exposures: Efforts included (1) launch of an external advisory board, (2) changes to the study protocol, (3) updates to the digital prescreener, (4) selection and deployment of 13 community-engaged research study sites, (5) development and deployment of local and centralized outreach efforts, and (6) development of a community-science partnership board., Main Outcomes and Measures: Screening and enrollment numbers from centralized and local outreach efforts, digital advertisement metrics, and digital prescreener completion., Results: A total of 91 participants enrolled in the trial via centralized and local outreach efforts, of which 22 (24.2%) identified as Latinx and 55 (60.4%) identified as Black (median [IQR] age, 65.6 [IQR, 61.5-72.5] years; 62 women [68.1%]). This represented a 267.6% increase in the monthly rate of enrollment (before: 1.11 per month; during: 4.08 per month) of underrepresented populations. For the centralized effort, social media advertisements were run between June 1, 2021, and July 31, 2022, which resulted in 2079 completed digital prescreeners, of which 1289 met criteria for subsequent site-level screening. Local efforts were run between June 1, 2021, to July 31, 2022. A total of 151 participants underwent site-level screening (100 from local efforts, 41 from centralized efforts, 10 from other sources)., Conclusions and Relevance: In this cross-sectional study of pilot inclusion efforts, a culturally informed, community-engaged approach increased the inclusion of Black and Latinx participants in an Alzheimer disease cohort study.

Background: The net benefit of aspirin cessation in older adults remains uncertain. This study aimed to use observational data to emulate a randomized trial of aspirin cessation versus continuation in older adults without cardiovascular disease (CVD)., Methods: Post hoc analysis using a target trial emulation framework applied to the immediate post-trial period (2017-2021) of a study of low-dose aspirin initiation in adults aged ≥ 70 years (ASPREE; NCT01038583). Participants from Australia and the USA were included if they were free of CVD at the start of the post-trial intervention period (time zero, T0) and had been taking open-label or randomized aspirin immediately before T0. The two groups in the target trial were as follows: aspirin cessation (participants who were taking randomized aspirin immediately before T0; assumed to have stopped at T0 as instructed) versus aspirin continuation (participants on open-label aspirin at T0 regardless of their randomized treatment; assumed to have continued at T0). The outcomes after T0 were incident CVD, major adverse cardiovascular events (MACE), all-cause mortality, and major bleeding during 3, 6, and 12 months (short-term) and 48 months (long-term) follow-up. Hazard ratios (HRs) comparing aspirin cessation to continuation were estimated from propensity-score (PS) adjusted Cox proportional-hazards regression models., Results: We included 6103 CVD-free participants (cessation: 5427, continuation: 676). Over both short- and long-term follow-up, aspirin cessation versus continuation was not associated with elevated risk of CVD, MACE, and all-cause mortality (HRs, at 3 and 48 months respectively, were 1.23 and 0.73 for CVD, 1.11 and 0.84 for MACE, and 0.23 and 0.79 for all-cause mortality, p > 0.05), but cessation had a reduced risk of incident major bleeding events (HRs at 3 and 48 months, 0.16 and 0.63, p < 0.05). Similar findings were seen for all outcomes at 6 and 12 months, except for a lowered risk of all-cause mortality in the cessation group at 12 months., Conclusions: Our findings suggest that deprescribing prophylactic aspirin might be safe in healthy older adults with no known CVD., (© 2024. The Author(s).)

Importance: Chronic kidney disease (CKD) is an often-asymptomatic complication of type 2 diabetes (T2D) that requires annual screening to diagnose. Patient-level factors linked to inadequate screening and treatment can inform implementation strategies to facilitate guideline-recommended CKD care., Objective: To identify risk factors for nonconcordance with guideline-recommended CKD screening and treatment in patients with T2D., Design, Setting, and Participants: This retrospective cohort study was performed at 20 health care systems contributing data to the US National Patient-Centered Clinical Research Network. To evaluate concordance with CKD screening guidelines, adults with an outpatient clinician visit linked to T2D diagnosis between January 1, 2015, and December 31, 2020, and without known CKD were included. A separate analysis reviewed prescription of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) and sodium-glucose cotransporter 2 (SGLT2) inhibitors in adults with CKD (estimated glomerular filtration rate [eGFR] of 30-90 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio [UACR] of 200-5000 mg/g) and an outpatient clinician visit for T2D between October 1, 2019, and December 31, 2020. Data were analyzed from July 8, 2022, through June 22, 2023., Exposures: Demographics, lifestyle factors, comorbidities, medications, and laboratory results., Main Outcomes and Measures: Screening required measurement of creatinine levels and UACR within 15 months of the index visit. Treatment reflected prescription of ACEIs or ARBs and SGLT2 inhibitors within 12 months before or 6 months following the index visit., Results: Concordance with CKD screening guidelines was assessed in 316 234 adults (median age, 59 [IQR, 50-67] years), of whom 51.5% were women; 21.7%, Black; 10.3%, Hispanic; and 67.6%, White. Only 24.9% received creatinine and UACR screening, 56.5% received 1 screening measurement, and 18.6% received neither. Hispanic ethnicity was associated with lack of screening (relative risk [RR], 1.16 [95% CI, 1.14-1.18]). In contrast, heart failure, peripheral arterial disease, and hypertension were associated with a lower risk of nonconcordance. In 4215 patients with CKD and albuminuria, 3288 (78.0%) received an ACEI or ARB; 194 (4.6%), an SGLT2 inhibitor; and 885 (21.0%), neither therapy. Peripheral arterial disease and lower eGFR were associated with lack of CKD treatment, while diuretic or statin prescription and hypertension were associated with treatment., Conclusions and Relevance: In this cohort study of patients with T2D, fewer than one-quarter received recommended CKD screening. In patients with CKD and albuminuria, 21.0% did not receive an SGLT2 inhibitor or an ACEI or an ARB, despite compelling indications. Patient-level factors may inform implementation strategies to improve CKD screening and treatment in people with T2D.

Background: Frailty is associated with chronic inflammation, which may be modified by aspirin. The purpose of this study was to determine whether low-dose aspirin reduces incident frailty in healthy older adult participants of the ASPirin in Reducing Events in the Elderly (ASPREE) trial., Methods: In the United States and Australia, 19 114 community-dwelling individuals aged ≥70 and older (U.S. minorities ≥65 years) and free of overt cardiovascular disease, persistent physical disability, and dementia were enrolled in ASPREE, a double-blind, placebo-controlled trial of 100-mg daily aspirin versus placebo. Frailty, a prespecified study end point, was defined according to a modified Fried frailty definition (Fried frailty) and the frailty index based on the deficit accumulation model (frailty index). Competing risk Cox proportional hazard models were used to compare time to incident frailty by aspirin versus placebo. Sensitivity analysis was conducted to include frailty data with and without imputation of missing data., Results: Over a median 4.7 years, 2 252 participants developed incident Fried frailty, and 4 451 had incident frailty according to the frailty index. Compared with placebo, aspirin treatment did not alter the risk of incident frailty (Fried frailty hazard ratio [HR]: 1.04, 95% confidence interval [CI] 0.96-1.13; frailty index HR: 1.03, 95% CI 0.97-1.09). The proportion of individuals classified as frail, and the trajectory in continuous frailty scores over time, were not different between the aspirin and placebo treatment groups. The results were consistent across a series of subgroups., Conclusions: Low-dose aspirin use in healthy older adults when initiated in older ages does not reduce risk of incident frailty or the trajectory of frailty., (Published by Oxford University Press on behalf of The Gerontological Society of America 2021.)

Celiac disease (CD) is not commonly associated with obesity; however, many patients are overweight or obese at time of diagnosis. As the number of people in the United States with obesity continues to rise, it is not known if the prevalence of obesity among patients with CD has also increased. This study utilized an electronic health record database incorporating over 360 individual hospitals in the United States (Explorys Incorporated, Cleveland, OH). Adult patients who had an esophagogastroduodenoscopy at least 1 day prior to reporting of CD from the years 2014 to 2018 formed the study population. From 2014 to 2018, 13,410 patients had a diagnosis of CD. The prevalence of obesity was 45,000/100,000 persons in this CD population. Prevalence of class I (BMI 30-34.9), II (BMI 35-39.9), and III (BMI > 40) obesity in patients with CD continued to rise over the 5-year span. Class I obesity had the highest prevalence and Class II the highest prevalence increase when obesity classes were compared. Clinicians should be aware of obesity as a comorbidity of increasing prevalence when providing longitudinal care for patients with CD., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: ASPirin in Reducing Events in the Elderly, a randomized, double-blind, placebo-controlled trial of daily low-dose aspirin (100 mg) in older adults, showed an increase in all-cause mortality, primarily due to cancer. In contrast, prior randomized controlled trials, mainly involving younger individuals, demonstrated a delayed cancer benefit with aspirin. We now report a detailed analysis of cancer incidence and mortality., Methods: 19 114 Australian and US community-dwelling participants aged 70 years and older (US minorities 65 years and older) without cardiovascular disease, dementia, or physical disability were randomly assigned and followed for a median of 4.7 years. Fatal and nonfatal cancer events, a prespecified secondary endpoint, were adjudicated based on clinical records., Results: 981 cancer events occurred in the aspirin and 952 in the placebo groups. There was no statistically significant difference between groups for all incident cancers (hazard ratio [HR] = 1.04, 95% confidence interval [CI] = 0.95 to 1.14), hematological cancer (HR = 0.98, 95% CI = 0.73 to 1.30), or all solid cancers (HR = 1.05, 95% CI = 0.95 to 1.15), including by specific tumor type. However, aspirin was associated with an increased risk of incident cancer that had metastasized (HR = 1.19, 95% CI = 1.00 to 1.43) or was stage 4 at diagnosis (HR = 1.22, 95% CI = 1.02 to 1.45), and with higher risk of death for cancers that presented at stages 3 (HR = 2.11, 95% CI = 1.03 to 4.33) or 4 (HR = 1.31, 95% CI = 1.04 to 1.64)., Conclusions: In older adults, aspirin treatment had an adverse effect on later stages of cancer evolution. These findings suggest that in older persons, aspirin may accelerate the progression of cancer and, thus, suggest caution with its use in this age group., (© The Author(s) 2020. Published by Oxford University Press.)

The role of aspirin for primary prevention in older adults with chronic kidney disease (CKD) is unclear. Therefore, post hoc analysis of the randomized controlled trial ASPirin in Reducing Events in the Elderly (ASPREE) was undertaken comparing 100 mg of enteric-coated aspirin daily against matching placebo. Participants were community dwelling adults aged 70 years and older in Australia, 65 years and older in the United States, all free of a history of dementia or cardiovascular disease and of any disease expected to lead to death within five years. CKD was defined as present at baseline if either eGFR under 60mL/min/1.73m 2 or urine albumin to creatinine ratio 3 mg/mmol or more. In 4758 participants with and 13004 without CKD, the rates of a composite endpoint (dementia, persistent physical disability or death), major adverse cardiovascular events and clinically significant bleeding in the CKD participants were almost double those without CKD. Aspirin's effects as estimated by hazard ratios were generally similar between CKD and non-CKD groups for dementia, persistent physical disability or death, major adverse cardiovascular events and clinically significant bleeding. Thus, in our analysis aspirin did not improve outcomes in older people while increasing the risk of bleeding, with mostly consistent effects in participants with and without CKD., (Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Cardiovascular drugs impact many pathways involved in depression pathophysiology and treatment. However, their distinct impact on mood is underrecognized and the literature is conflicting. Therefore, using a very large and well-characterised sample of older adults with hypertension, we aimed to investigate the prevalence of depressive symptoms in users of different antihypertensive classes. We analysed baseline data from 14,195 older individuals with hypertension enroled in a large clinical trial. Median age was 75 years. The association of antihypertensive use by class and depression prevalence, as measured by a validated depression scale, was determined using logistic regression models. Multivariable logistic models were implemented to account for important confounding factors. Our analyses showed a positive association between depressive symptoms and the use of beta blockers (BB) (OR: 1.37; 95% CI: 1.17-1.60, p < 0.01), compared with users of other antihypertensive classes. All other classes of antihypertensives (including angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, and calcium channel blockers) were not significantly associated with depressive symptoms. In secondary analysis, this relationship was stronger for lipophilic (39%) and nonselective BB (52%) compared with hydrophilic (26%) and selective medications (31%), respectively. This study adds further evidence for a probable association between BB and depression in a large sample of older adults with hypertension and no history of cardiovascular disease or heart failure. These findings should regenerate interest and increase awareness of clinicians about the possible adverse effects of these medications in an otherwise healthy older population.

Comparisons of communities across cities are rare in social epidemiology. Our prior work exploring racial/ethnic segregation and the prevalence of low birth weight (LBW) in communities from two large urban cities showed a strong relationship in Chicago and a very weak relationship in Toronto. This study extends that work by examining the association between racial/ethnic minority segregation and LBW in total of 307 communities in five North American cities: Baltimore, Boston, Chicago, Philadelphia, and Toronto. We used Pearson correlation coefficients and OLS regression models to examine potential variability in the association between racial/ethnic minority segregation and LBW, controlling for community-level unemployment. In a combined model with community-level data from all cities, a 10% increase in minority composition is associated with a 0.7% increase in LBW. While racial/ethnic minority segregation and unemployment are not associated with LBW in Toronto, these social determinants have strong and significant associations with LBW across communities in the four US cities in the analysis. Subsequent models revealed opposite effects for percentage non-Hispanic Black and percentage Hispanic. Across communities in the US cities in this analysis, there is considerable similarity in the strength of the effect of racial/ethnic segregation on LBW. Future work should incorporate communities from additional cities, looking to identify community assets and public policies that allow some minority communities to thrive, while other minority communities suffer from a high prevalence of LBW. More work is also needed on the generalizability of these patterns to other health outcomes.

Objectives: To investigate the association between depressive symptoms and several medical morbidities, and their combination, in a large older population., Design: Cross-sectional study of baseline data from the ASPirin in Reducing Events in the Elderly (ASPREE) trial., Setting: Multicentric study conducted in Australia and the United States., Participants: A total of 19,110 older adults (mean age = 75 years [standard deviation = ±4.5])., Measurements: Depressive symptoms were measured using the Center for Epidemiological Studies Depression (CES-D 10) scale. Medical morbidities were defined according to condition-specific methods. Logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) to test associations before and after accounting for possible confounders., Results: Depressive symptoms were significantly associated with obesity (OR = 1.19; 95% CI = 1.07-1.32), diabetes (OR = 1.22; 95% CI = 1.05-1.42), gastroesophageal reflux disease (GERD) (OR = 1.41; 95% CI = 1.28-1.57), metabolic syndrome (OR = 1.16; 95% CI = 1.03-1.29), osteoarthritis (OR = 1.41; 95% CI = 1.27-1.57), respiratory conditions (OR = 1.25; 95% CI = 1.10-1.42), history of cancer (OR = 1.19; 95% CI = 1.05-1.34), Parkinson's disease (OR = 2.56; 95% CI = 1.83-3.56), polypharmacy (OR = 1.60; 95% CI = 1.44-1.79), and multimorbidity (OR = 1.29; 95% CI = 1.12-1.49). No significant association was observed between depressive symptoms and hypertension, chronic kidney disease, dyslipidemia, and gout (P > .05). A significant dose-response relationship was evident between the number of medical comorbidities and the prevalence of depression (OR = 1.18; 95% CI = 1.13-1.22)., Conclusion: Late-life depressive symptoms are significantly associated with several medical morbidities, and there appears to be a cumulative effect of the number of somatic diseases on the prevalence of depression. These findings augment the evidence for a complex relationship between mental and physical health in an otherwise healthy older population and might guide clinicians toward early recognition of high-risk individuals. J Am Geriatr Soc 68:1834-1841, 2020., (© 2020 The American Geriatrics Society.)

Up to 40% of patients with primary biliary cholangitis have an incomplete response to first-line treatment with ursodeoxycholic acid. Obeticholic acid was approved by the US Food and Drug Administration in 2016 as a second-line treatment for patients with primary biliary cholangitis who are unresponsive to ursodeoxycholic acid; however, approximately 50% of patients might need additional treatments to reach therapeutic goals. A considerable need exists for effective treatment options to prevent progression to liver transplantation or death in these patients. Drugs that might modulate immunological abnormalities in primary biliary cholangitis have been studied but their effectiveness varies. Budesonide, ciclosporin, and rituximab have shown potential in modifying the disease process. Bezafibrate, a pan-peroxisome proliferator-activated receptor agonist, has been shown to ameliorate deranged bile acid homoeostasis and attenuate raised concentrations of liver enzymes associated with primary biliary cholangitis. As the mechanisms underlying the pathogenesis and progression of primary biliary cholangitis are further clarified, specific targeted therapies are under development with promising early results. Various therapeutic target bile acid homeostasis, immune dysfunction, and fibrogenetic pathways are being studied. A better understanding of the biochemical and clinical effects of the therapies in development bear discussion, both to guide the discovery of new therapies and to inform clinicians so that rational treatment regimens can be tailored to patients once they become available., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The Rush Alzheimer's Disease Center (RADC) conducts 5 harmonized prospective clinical-pathologic cohort studies of aging - with 1 study, the Latino Core, focused exclusively on Latinxs, 2 studies consisting of mostly non-Latinx whites, and 2 studies of mostly non-Latinx blacks. This paper contextualizes the Latino Core within the other 4 harmonized RADC cohort studies. The overall aim of the paper is to provide information from the RADC, so that researchers can learn from our participants and procedures to better advance the science of Alzheimer's disease and related dementias in Latinxs. We describe an annual clinical evaluation that assesses risk factors for Alzheimer's dementia among older adults without known dementia at enrollment. As all RADC cohort studies offer brain donation as a part of research participation, we discuss our approach to brain donation and subsequent participant decision-making among older Latinxs. We also summarize baseline characteristics of older Latinxs across the 5 RADC cohort studies in relation to the baseline characteristics of non-Latinx blacks and non-Latinx whites. Finally, we outline challenges and considerations as well as potential next steps in cognitive aging research with older Latinxs., (© 2020 S. Karger AG, Basel.)

Objective: To test the hypothesis that Alzheimer's disease and related neuropathologies contribute to the association between hospitalization and cognitive decline in old age., Methods: As part of a longitudinal clinical-pathologic cohort study, 526 older persons (mean age at death = 90.9 years, 71% female) without dementia at baseline completed annual cognitive testing and were autopsied at death. Hospitalization information was obtained from linked Medicare claims records. Neuropathologic examination assessed β-amyloid burden, tau tangle density, neocortical Lewy bodies, hippocampal sclerosis, chronic gross and microscopic cerebral infarcts, and transactive response DNA binding protein 43 kDa., Results: Over a mean of 5.1 years, a total of 1,383 hospitalizations occurred, and the mean annual rate of hospitalization was 0.5 (standard deviation = 0.6, median = 0.4). Higher rate of hospitalization was not directly related to higher burden for any of the neuropathologic markers. Higher rate of hospitalization was associated with more rapid cognitive decline (estimate = -0.042, standard error [SE] = 0.012, p < 0.001), and after controlling for all 7 neuropathologic markers, the association was essentially the same (estimate = -0.040, SE = 0.013, p = 0.002). In a multivariable model with 3-way interactions of neuropathologic markers with hospitalization rate and time, the association between hospitalization rate and faster cognitive decline was greater in persons with more tangle pathology (estimate for interaction = -0.007, SE = 0.002, p = 0.002) and in persons with neocortical Lewy bodies (estimate for interaction = -0.117, SE = 0.042, p = 0.005)., Interpretation: Older persons with more hospitalizations experienced faster rates of cognitive decline, and this association was more pronounced in persons with more tau tangle density and with neocortical Lewy body pathologies. ANN NEUROL 2019;86:844-852., (© 2019 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.)

Background: Statin use has been frequently associated with depressive symptoms in an older population. However, the nature of this association is uncertain in the literature. In this study, we aimed to investigate the association of statin intake and the prevalence of depressive symptoms in healthy community-dwelling older adults living in Australia and the USA., Methods: We analysed baseline data from 19,114 participants, over 70 years of age (over 65 years of age, if from an ethnic minority). The association of self-reported statin use and prevalence of depressive symptoms, as measured by a validated depression scale [Center for Epidemiological Studies Depression Scale (CES-D 10)], was determined using logistic regression models. Multivariable logistic models were implemented to account for important demographics and other lifestyle and socioeconomic factors, such as sex, age, living status, education and smoking history., Results: A total of 5987 individuals were statin users. Of those, 633 (10.6%) had depressive symptoms (CES-D 10 cut-off ≥ 8), compared with 1246 (9.5%) of the non-statin users. In the unadjusted model, statin use was associated with an increase in prevalence of depressive symptoms (odds ratio 1.13, confidence interval 1.02-1.25, p = 0.02). However, after adjusting for important demographic and socioeconomic factors, the use of statins was not significantly associated with depressive symptoms (odds ratio 1.09, confidence interval 0.98-1.20, p = 0.11). In secondary analyses, only simvastatin was marginally associated with an increased prevalence of depressive symptoms. Statins were associated with a decreased prevalence of depressive symptoms in individuals with severe obesity (body mass index > 35 kg/m 2 ) and an increased prevalence in participants between 75 and 84 years of age., Conclusion: This study in a large community-dwelling older population did not show any association of statins with late-life depressive symptoms, after accounting for important socioeconomic and demographic factors. Confounding by indication is an important issue to be addressed in future pharmacoepidemiologic studies of statins.

Objective: To determine whether emergent and urgent (nonelective) hospitalizations are associated with faster acceleration of cognitive decline compared to elective hospitalizations, accounting for prehospital decline., Methods: Data came from the Rush Memory and Aging Project, a prospective cohort study of community-dwelling older persons without baseline dementia. Annual measures of cognition via a battery of 19 tests were linked to 1999 to 2010 Medicare claims records., Results: Of 777 participants, 460 (59.2%) were hospitalized over a mean of 5.0 (SD = 2.6) years; 222 (28.6%) had at least one elective and 418 (53.8%) at least one nonelective hospitalization. Mixed-effects regression models estimated change in global cognition before and after each type of hospitalization compared to no hospitalization, adjusted for age, sex, education, medical conditions, length of stay, surgery, intensive care unit, and comorbidities. Persons who were not hospitalized had a mean loss of 0.051 unit global cognition per year. In comparison, there was no significant difference in rate of decline before (0.044 unit per year) or after (0.048 unit per year) elective hospitalizations. In contrast, decline before nonelective hospitalization was faster (0.076 unit per year; estimate = -0.024, SE = 0.011, p = 0.032), and accelerated by 0.036 unit (SE = 0.005, p < 0.001) to mean loss of 0.112 unit per year after nonelective hospitalizations, more than doubling the rate in those not hospitalized., Conclusions: Nonelective hospitalizations are related to more dramatic acceleration in cognitive decline compared to elective hospitalizations, even after accounting for prehospital decline. These findings may inform which hospital admissions pose the greatest risk to the cognitive health of older adults., (© 2019 American Academy of Neurology.)

Background & Aims: It is not clear whether digital single-operator cholangioscopy (D-SOC) with electrohydraulic and laser lithotripsy is effective in removal of difficult biliary stones. We investigated the safety and efficacy of D-SOC with electrohydraulic and laser lithotripsy in an international, multicenter study of patients with difficult biliary stones., Methods: We performed a retrospective analysis of 407 patients (60.4% female; mean age, 64.2 years) who underwent D-SOC for difficult biliary stones at 22 tertiary centers in the United States, United Kingdom, or Korea from February 2015 through December 2016; 306 patients underwent electrohydraulic lithotripsy and 101 (24.8%) underwent laser lithotripsy. Univariate and multivariable analyses were performed to identify factors associated with technical failure and the need for more than 1 D-SOC electrohydraulic or laser lithotripsy session to clear the bile duct., Results: The mean procedure time was longer in the electrohydraulic lithotripsy group (73.9 minutes) than in the laser lithotripsy group (49.9 minutes; P < .001). Ducts were completely cleared (technical success) in 97.3% of patients (96.7% of patients with electrohydraulic lithotripsy vs 99% patients with laser lithotripsy; P = .31). Ducts were cleared in a single session in 77.4% of patients (74.5% by electrohydraulic lithotripsy and 86.1% by laser lithotripsy; P = .20). Electrohydraulic or laser lithotripsy failed in 11 patients (2.7%); 8 patients were treated by surgery. Adverse events occurred in 3.7% patients and the stone was incompletely removed from 6.6% of patients. On multivariable analysis, difficult anatomy or cannulation (duodenal diverticula or altered anatomy) correlated with technical failure (odds ratio, 5.18; 95% confidence interval, 1.26-21.2; P = .02). Procedure time increased odds of more than 1 session of D-SOC electrohydraulic or laser lithotripsy (odds ratio, 1.02; 95% confidence interval, 1.01-1.03; P < .001)., Conclusions: In a multicenter, international, retrospective analysis, we found D-SOC with electrohydraulic or laser lithotripsy to be effective and safe in more than 95% of patients with difficult biliary stones. Fewer than 5% of patients require additional treatment with surgery and/or extracorporeal shockwave lithotripsy to clear the duct., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Rationale Aspirin has positive and negative effects on a number of age-related chronic conditions and there is uncertainty regarding its role in primary prevention in people aged 70 years and over. Aims To assess whether daily active treatment of 100 mg enteric-coated aspirin will extend the duration of disability-free life in healthy older participants. Design A double-blind, randomized, placebo-controlled primary prevention trial undertaken in Australia and the United States with careful adjudication of endpoints including stroke. Study outcome In Australia 16,703 individuals were recruited through general practices across five states and territories, and in the United States, 2411 participants were recruited through 34 clinical sites across the country. Follow-up of participants will finish at the end of 2017 with average follow-up exceeding 4.25 years per person. Discussion The statistical analysis plan for ASPREE, finalized after closure of recruitment but before the end of patient follow-up, outlines the primary analyses and a range of subgroup and sensitivity analyses. (International Standard Randomized Controlled Trial Number Register ISRCTN83772183 and clinicaltrials.gov Number NCT01038583).

Objective: Older persons with HIV are at risk for impaired cognition, yet there is limited information on modifiable factors associated with neurocognitive function in this group., Design: This is a cross-sectional observational study of cognitive activities and neurocognitive function., Methods: We examined the relation between frequency of cognitive activity and current neurocognitive performance in 176 older persons with HIV [70% African American, 76% men; mean age = 58.7 (SD = 5.5); mean education = 13.2 (SD = 2.8)]., Results: In linear regression models adjusted for demographic variables, we found that higher frequency of cognitive activity was associated with better cognition in global cognition, semantic memory, and perceptual speed. Subsequent models that examined the role of race demonstrated that the association was significant only among Blacks for global cognition, episodic memory, working memory, and perceptual speed (interaction of cognitive activity by race: Estimate range = 0.38-0.55; all P < 0.05)., Conclusion: Greater frequency of cognitive activity is associated with better neurocognitive function in older persons with HIV, particularly older Blacks. Longitudinal studies are needed to assess the relation of cognitive activity to change in neurocognitive function in older persons with HIV., Competing Interests: Alan L. Landay is on the Scientific Advisory Board for Merck. Lisa L. Barnes is the recipient of grants mentioned above and has no other conflicts of interest. For the remaining authors no conflict of interests or funding sources have been declared.

Background & Aims: Plastic stents, placed via endoscopy to drain pancreatic fluid collections (PFCs), require repeat access. Covered metal stents are larger in diameter and can be inserted in a single step, but can migrate. We evaluated the safety and efficacy of a lumen-apposing, covered, self-expanding metal stent (LACSEMS) for PFC drainage., Methods: We performed a prospective study of the outcomes of stent placement in 33 patients (18 men; age, 53 ± 14 y; 28 with chronic pancreatitis) with symptomatic pancreatic pseudocysts and walled-off necrosis (≥ 6 cm with ≥ 70% fluid content). Subjects were enrolled at 7 tertiary care centers (6 in the United States and 1 in Europe) from October 2011 through August 2013. Cystenterostomies were created based on endoscopist preference. Safety outcomes included infection, bleeding, perforation, tissue injury, and stent migration. Efficacy end points included LACSEMS placement, patency, and removal, as well as 50% or more reduction in PFCs., Results: The mean size of the patients' PFCs was 9 ± 3.3 cm. LACSEMSs were placed successfully via endoscopic ultrasound guidance in 30 patients (91%); the remaining 3 patients received 2 double-pigtail stents. One subject could not be evaluated because of a pseudoaneurysm. In the patients receiving LACSEMS, PFCs resolved in 27 of 29 (93%). Overall, PFCs resolved in 30 of 33 patients (91%). Endoscopic debridement through the LACSEMS was conducted in 11 subjects. Complications (15%) included abdominal pain (n = 3), spontaneous stent migration, back pain (n = 1), access-site infection, and stent dislodgement (n = 1)., Conclusions: LACSEMS were placed successfully in 91% of subjects with PFCs. Overall, 93% had PFC resolution. Advantages of LACSEMSs over other stents include single-step deployment and the ability to perform endoscopic debridement with minimal stent migration. Clinicaltrials.gov: NCT01419769., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Data on overtube-assisted enteroscopy to facilitate ERCP in patients with surgically altered pancreaticobiliary anatomy, or long-limb surgical bypass, is limited., Objective: To evaluate and compare ERCP success by using single-balloon (SBE), double-balloon (DBE), or rotational overtube enteroscopy., Design: Consecutive patients identified retrospectively., Setting: Eight U.S. referral centers., Patients: Long-limb surgical bypass patients with suspected pancreaticobiliary diseases., Intervention: Overtube-assisted enteroscopy ERCP., Main Outcome Measurements: Enteroscopy success: visualizing the pancreaticobiliary-enteric anastomosis or papilla. ERCP success: completing the intended pancreaticobiliary intervention. Clinical success: greater than 50% reduction in abdominal pain or level of hepatic enzyme elevations or resolution of jaundice., Results: From January 2008 through October 2009, 129 patients had 180 enteroscopy-ERCPs. Anatomy was Roux-en-Y: gastric bypass (n = 63), hepaticojejunostomy (n = 45), postgastrectomy (n = 6), Whipple procedure (n = 10), and other (n = 5). ERCP success was 81 of 129 (63%). Enteroscopy success: 92 of 129 (71%), of whom 81 of 92 (88%) achieved ERCP success. Reasons for ERCP failure (n = 48): afferent limb entered but pancreaticobiliary anastomosis and/or papilla not reached (n = 23), cannulation failure (n = 11), afferent limb angulation (n = 8), and jejunojejunostomy not identified (n = 6). Select interventions: anastomotic stricturoplasty (cautery ± dilation, n = 16), stone removal (n = 21), stent (n = 25), and direct cholangioscopy (n = 11). ERCP success rates were similar between Roux-en-Y gastric bypass and other long-limb surgical bypass and among SBE, DBE, and rotational overtube enteroscopy. Complications were 16 of 129, 12.4%., Limitations: Retrospective study., Conclusion: (1) ERCP is successful in nearly two-thirds of long-limb surgical bypass patients and in 88% when the papilla or pancreaticobiliary-enteric anastomosis is reached. (2) Enteroscopy success in long-limb surgical bypass is similar among SBE, DBE, and rotational overtube enteroscopy methods. (3) Referral of long-limb surgical bypass patients who require ERCP to high-volume institutions may be considered before more invasive percutaneous or surgical alternatives., (Copyright © 2013 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

Background: Factors contributing to gait difficulties in elderly persons are considered to be multifactorial and are not well understood. The purpose of this study was to examine the association of blood pressure (BP) with change in lower limb function in older persons., Methods: Eight hundred eighty-eight older Catholic clergy members without baseline dementia or Parkinson's disease were recruited from about 40 groups across the United States. At baseline, BP was measured, the presence of vascular diseases and diabetes was recorded, cognitive function was assessed, and medications were inspected. At baseline and subsequent annual visits, gait and balance were assessed using performance-based tasks from which a previously established composite measure of lower limb function was derived., Results: In a general estimating equation analysis controlling for age, education, and gender, a 10 mmHg increment in systolic blood pressure (SBP) was associated with greater decline in lower limb function (estimate of interaction = -6.35 x 10(-3), standard error = 2.49 x 10(-3), p =.011). Thus, on average, lower limb function declined 28.7% faster in persons with an SBP of 160 mmHg than in persons with an SBP of 120 mmHg. This effect was unchanged after controlling for baseline vascular diseases, diabetes, or cognition. However, censoring individuals who developed stroke during the study made the relationship between SBP and change in lower limb function nonsignificant., Conclusions: SBP may be associated with decline in lower limb function in older persons.

Purpose: To examine the relation of systolic and diastolic blood pressure to incident Alzheimer's disease (AD) and rate of cognitive change., Methods: Longitudinal cohort study with annual clinical evaluations. At baseline, blood pressure was measured, apolipoprotein E (APOE) genotyping was performed, and medications were reviewed., Results: 824 older Catholic clergy members without baseline dementia were recruited from across the United States. During a mean of about 6 years of observation, 151 persons developed AD. In a proportional hazards model adjusted for age, sex and education, neither systolic (relative risk = 0.995; 95% CI: 0.986, 1.004, p = 0.249) nor diastolic (relative risk = 1.000; 95% CI: 0.985, 1.015, p = 0.975) blood pressure was related to AD incidence. In mixed effects models, neither systolic nor diastolic blood pressure was related to level or to annual rate of change on a global measure of cognition. These results did not change in subsequent models that accounted for the use of medications with antihypertensive properties or for the possession of an APOE epsilon4 allele., Conclusions: In a cohort of older persons with a majority taking medications with antihypertensive properties, we did not find a relationship between blood pressure and risk of AD or cognitive decline.