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Predicting Bleeding Risk to Guide Aspirin Use for the Primary Prevention of Cardiovascular Disease: A Cohort Study: Annals of Internal Medicine: Vol 170, No 6

Background: Many prognostic models for cardiovascular risk can be used to estimate aspirin's absolute benefits, but few bleeding risk models are available to estimate its likely harms. Objective: To develop prognostic bleeding risk models among persons in whom aspirin might be considered for the primary prevention of cardiovascular disease (CVD). Design: Prospective cohort study. Setting: New Zealand primary care. Participants: The study cohort comprised 385 191 persons aged 30 to 79 years whose CVD risk was assessed between 2007 and 2016. Those with indications for or contraindications to aspirin and those who were already receiving antiplatelet or anticoagulant therapy were excluded. Measurements: For each sex, Cox proportional hazards models were developed to predict major bleeding risk; participants were censored at the earliest of the date on which they first met an exclusion criterion, date of death, or study end date (30 June 2017). The main models included the following predictors: demographic characteristics (age, ethnicity, and socioeconomic deprivation), clinical measurements (systolic blood pressure and ratio of total–high-density lipoprotein cholesterol), family history of premature CVD, medical history (smoking, diabetes, bleeding, peptic ulcer disease, cancer, chronic liver disease, chronic pancreatitis, or alcohol-related conditions), and medication use (nonsteroidal anti-inflammatory agents, corticosteroids, and selective serotonin reuptake inhibitors). Results: During 1 619 846 person-years of follow-up, 4442 persons had major bleeding events (of which 313 [7%] were fatal). The main models predicted a median 5-year bleeding risk of 1.0% (interquartile range, 0.8% to 1.5%) in women and 1.1% (interquartile range, 0.7% to 1.6%) in men. Plots of predicted-against-observed event rates showed good calibration throughout the risk range. Limitation: Hemoglobin level, platelet count, and body mass index were excluded from the main models because of high numbers of missing values, and the models were not externally validated in non–New Zealand populations. Conclusion: Prognostic bleeding risk models were developed that can be used to estimate the absolute bleeding harms of aspirin among persons in whom aspirin is being considered for the primary prevention of CVD. Primary Funding Source: The Health Research Council of New Zealand.

Local Area Variation in Morbidity Among Low-Income, Older Adults in the United States: A Cross-sectional Study: Annals of Internal Medicine: Vol 171, No 7

Background: Recent studies have reported that low-income adults living in more affluent areas of the United States have longer life expectancies. Less is known about the relationship between the affluence of a geographic area and morbidity of the low-income population. Objective: To evaluate the association between the prevalence of chronic conditions among low-income, older adults and the economic affluence of a local area. Design: Cross-sectional association study. Setting: Medicare in 2015. Participants: 6 363 097 Medicare beneficiaries aged 66 to 100 years with a history of low-income support under Medicare Part D. Measurements: Adjusted prevalence of 48 chronic conditions was computed for 736 commuting zones (CZs). Factor analysis was used to assess spatial covariation of condition prevalence and to construct a composite condition prevalence index for each CZ. The association between morbidity and area affluence was measured by comparing the average of condition prevalence index across deciles of median CZ house values. Results: The mean age of study participants was 77.7 years (SD, 8.2); 67% were women, and 61% were white. The crude prevalence of 48 chronic conditions ranged from 72.5 per 100 for hypertension to 0.6 per 100 for posttraumatic stress disorder. The prevalence of these 48 chronic conditions was highly spatially correlated. Composite condition prevalence was on average substantially lower in more affluent CZs. Limitation: Low-income status measured on the basis of receipt of Medicare Part D low-income subsidies and not capturing persons not enrolled in Medicare Part D. Conclusion: Low-income, older adults living in more affluent areas of the country are healthier, and areas with poor health in the low-income, older adult population tend to have a high prevalence of most chronic conditions. Primary Funding Source: National Institute on Aging.

Lipophilic Statins and Risk for Hepatocellular Carcinoma and Death in Patients With Chronic Viral Hepatitis: Results From a Nationwide Swedish Population

Background: Whether statin type influences hepatocellular carcinoma (HCC) incidence or mortality in chronic hepatitis B or C virus infection is unknown. Objective: To assess the relationship between lipophilic or hydrophilic statin use and HCC incidence and mortality in a nationwide population with viral hepatitis. Design: Prospective propensity score (PS)–matched cohort. Setting: Swedish registers, 2005 to 2013. Participants: A PS-matched cohort of 16 668 adults (8334 who initiated statin use [6554 lipophilic and 1780 hydrophilic] and 8334 nonusers) among 63 279 eligible adults. Measurements: Time to incident HCC, ascertained from validated registers. Statin use was defined from filled prescriptions as 30 or more cumulative defined daily doses (cDDDs). Results: Compared with matched nonusers, 10-year HCC risk was significantly lower among lipophilic statin users (8.1% vs. 3.3%; absolute risk difference [RD], −4.8 percentage points [95% CI, −6.2 to −3.3 percentage points]; adjusted subdistribution hazard ratio [aHR], 0.56 [CI, 0.41 to 0.79]) but not hydrophilic statin users (8.0% vs. 6.8%; RD, −1.2 percentage points [CI, −2.6 to 0.4 percentage points]; aHR, 0.95 [CI, 0.86 to 1.08]). The inverse association between lipophilic statins and HCC risk seemed to be dose-dependent. Compared with nonusers, 10-year HCC risk was lowest with 600 or more lipophilic statin cDDDs (8.4% vs. 2.5%; RD, −5.9 percentage points [CI, −7.6 to −4.2 percentage points]; aHR, 0.41 [CI, 0.32 to 0.61]), and 10-year mortality was significantly lower among both lipophilic (15.2% vs. 7.3%; RD, −7.9 percentage points [CI, −9.6 to −6.2 percentage points]) and hydrophilic (16.0% vs. 11.5%; RD, −4.5 percentage points [CI, −6.0 to −3.0 percentage points]) statin users. Limitation: Lack of lipid, fibrosis, or HCC surveillance data. Conclusion: In a nationwide viral hepatitis cohort, lipophilic statins were associated with significantly reduced HCC incidence and mortality. An association between hydrophilic statins and reduced risk for HCC was not found. Further research is needed to determine whether lipophilic statin therapy is feasible for prevention of HCC. Primary Funding Source: None.

Scam Awareness Related to Incident Alzheimer Dementia and Mild Cognitive Impairment: A Prospective Cohort Study: Annals of Internal Medicine: Vol 170, No 10

Background: Decreased scam awareness may be an early indicator of impending Alzheimer dementia and its precursor, mild cognitive impairment, but prior studies have not systematically examined the associations between scam awareness and adverse cognitive outcomes. Objective: To test the hypothesis that low scam awareness is associated with increased risk for incident Alzheimer dementia, mild cognitive impairment, and Alzheimer disease pathology in the brain. Design: Prospective cohort study of aging. Setting: Community-based study in the greater Chicago metropolitan area. Participants: 935 older persons initially free of dementia. Measurements: Scam awareness was measured via questionnaire, incident Alzheimer dementia and mild cognitive impairment were documented in detailed annual cognitive and clinical evaluations, and Alzheimer disease neuropathology was quantified after death among a subset of persons who died (n = 264). Proportional hazards models examined associations between scam awareness and incident Alzheimer dementia and mild cognitive impairment. Regression models examined associations between scam awareness and Alzheimer disease pathology, particularly β-amyloid burden and tau tangle density. Results: During a mean of about 6 years (SD, 2.4) of observation, 151 persons (16.1%) developed Alzheimer dementia. Low scam awareness was associated with increased risk for Alzheimer dementia (hazard ratio [HR], 1.56 [95% CI, 1.21 to 2.01]; P < 0.001), such that each 1-unit increase in scam score (indicating lower awareness) was associated with about a 60% increase in dementia risk. Low scam awareness was also associated with increased risk for mild cognitive impairment (HR, 1.47 [CI, 1.20 to 1.81]; P < 0.001). These associations persisted even after adjustment for global cognitive function. Finally, low scam awareness was associated with a higher burden of Alzheimer pathology in the brain, particularly β-amyloid (estimated increase [±SE] in β-amyloid per 1-unit increase in scam score, 0.22 ± 0.10 unit; P = 0.029). Limitation: The measure of scam awareness used here is too weak for prediction at the individual level. Conclusion: Low scam awareness among older persons is a harbinger of adverse cognitive outcomes and is associated with Alzheimer disease pathology in the brain. Primary Funding Source: National Institute on Aging.

Dual Receipt of Prescription Opioids From the Department of Veterans Affairs and Medicare Part D and Prescription Opioid Overdose Death Among Veterans: A Nested Case–Control Study: Annals of Internal Medicine: Vol 170, No 7

Background: More than half of enrollees in the U.S. Department of Veterans Affairs (VA) are also covered by Medicare and can choose to receive their prescriptions from VA or from Medicare-participating providers. Such dual-system care may lead to unsafe opioid use if providers in these 2 systems do not coordinate care or if prescription use is not tracked between systems. Objective: To evaluate the association between dual-system opioid prescribing and death from prescription opioid overdose. Design: Nested case–control study. Setting: VA and Medicare Part D. Participants: Case and control patients were identified from all veterans enrolled in both VA and Part D who filled at least 1 opioid prescription from either system. The 215 case patients who died of a prescription opioid overdose in 2012 or 2013 were matched (up to 1:4) with 833 living control patients on the basis of date of death (that is, index date), using age, sex, race/ethnicity, disability, enrollment in Medicaid or low-income subsidies, managed care enrollment, region and rurality of residence, and a medication-based measure of comorbid conditions. Measurements: The exposure was the source of opioid prescriptions within 6 months of the index date, categorized as VA only, Part D only, or VA and Part D (that is, dual use). The outcome was unintentional or undetermined-intent death from prescription opioid overdose, identified from the National Death Index. The association between this outcome and source of opioid prescriptions was estimated using conditional logistic regression with adjustment for age, marital status, prescription drug monitoring programs, and use of other medications. Results: Among case patients, the mean age was 57.3 years (SD, 9.1), 194 (90%) were male, and 181 (84%) were non-Hispanic white. Overall, 60 case patients (28%) and 117 control patients (14%) received dual opioid prescriptions. Dual users had significantly higher odds of death from prescription opioid overdose than those who received opioids from VA only (odds ratio [OR], 3.53 [95% CI, 2.17 to 5.75]; P < 0.001) or Part D only (OR, 1.83 [CI, 1.20 to 2.77]; P = 0.005). Limitation: Data are from 2012 to 2013 and cannot capture prescriptions obtained outside the VA or Medicare Part D systems. Conclusion: Among veterans enrolled in VA and Part D, dual use of opioid prescriptions was independently associated with death from prescription opioid overdose. This risk factor for fatal overdose among veterans underscores the importance of care coordination across health care systems to improve opioid prescribing safety. Primary Funding Source: U.S. Department of Veterans Affairs.

How Would You Manage This Patient With Gout?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center: Annals of Internal Medicine: Vol 169, No 11

Gout is the most common form of inflammatory arthritis. In 2012, the American College of Rheumatology (ACR) issued a guideline, which was followed in 2017 by one from the American College of Physicians (ACP). The guidelines agree on treating acute gout with a corticosteroid, nonsteroidal anti-inflammatory drug, or colchicine and on not initiating long-term urate-lowering therapy (ULT) for most patients after a first gout attack and in those whose attacks are infrequent (<2 per year). However, they differ on treatment of both recurrent gout and problematic gout. The ACR advocates a “treat-to-target” approach, and the ACP did not find enough evidence to support this approach and offered an alternative strategy that bases intensity of ULT on the goal of avoiding recurrent gout attacks (“treat-to-avoid-symptoms”) with no monitoring of urate levels. They also disagree on the role of a gout-specific diet. Here, a general internist and a rheumatologist discuss these guidelines; they debate how they would manage an acute attack of gout, if and when to initiate ULT, and the goals for ULT. Lastly, they offer specific advice for a patient who is uncertain about whether to begin this therapy.