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We assessed whether social isolation (SI), social support (SS), and subtypes of SS were associated with self-rated health trajectories and clinical heart failure (HF) outcomes among participants with incident HF hospitalizations. We included 2967 Atherosclerosis Risk in Communities study participants with incident HF hospitalization after Visit 2 (1990–1992). SI, SS, and subtypes of SS were measured at Visit 2. We identified incident HF hospitalization as ICD-9 code 428 and physician adjudicated events; on average HF occurred 17 (SD 8) years after Visit 2. We assessed associations with trajectories of annually measured self-rated health in the 4 years prior to and after incident HF hospitalization (excellent/good self-rated health on a 0–100 scale), using linear mixed effects models. We calculated hazard ratios (HR) and 95% confidence intervals (CIs) for associations with time to first all-cause rehospitalization and all-cause mortality using Cox proportional hazard models. Low overall SS had a 5.8 point (95% CI 7.8, 3.8) lower self-rated health value over time than high SS; associations of subtypes of SS with this outcome were similar. Low belonging SS was associated with greater days to first rehospitalization (HR 0.85; 95% CI 0.79, 0.96) compared to the highest tertile; however, belonging SS was not associated with mortality (HR 1.05; 95% CI 0.95, 1.17). Being socially isolated/high risk for SI was associated with greater hazard of all-cause mortality among females (HR 1.57; 95% CI 1.20, 2.06) but not males (HR 0.95; 95% CI 0.75, 1.19), compared to low SI. SI and SS were not associated with number of hospitalizations in the first year or percent of first year spent at home.

Most strategies for prevention of venous thromboembolism focus on preventing recurrent events. Yet, primary prevention might be possible through approaches targeting the whole population or high-risk patients. To inform possible prevention strategies, population-based information on the ability of genetic risk scores to identify risk of incident venous thromboembolism is needed. We used proportional hazards regression to relate two published genetic risk scores (273-variants versus 5-variants) with venous thromboembolism incidence in the Atherosclerosis Risk in Communities Study (ARIC) cohort (n = 11,292), aged 45-64 at baseline, drawn from 4 US communities. Over a median of 28 years, ARIC identified 788 incident venous thromboembolism events. Incidence rates rose more than two-fold across quartiles of the 273-variant genetic risk score: 1.7, 2.7, 3.4 and 4.0 per 1,000 person-years. For White participants, age, sex, and ancestry-adjusted hazard ratios (95% confidence intervals) across quartiles were strong [1 (reference), 1.30 (0.99,1.70), 1.85 (1.43,2.40), and 2.58 (2.04,3.28)] but weaker for Black participants [1, 1.05 (0.63,1.75), 1.37 (0.84,2.22), and 1.32 (0.80,2.20)]. The 5-variant genetic risk score showed a less steep gradient, with hazard ratios in Whites of 1, 1.17 (0.89,1.54), 1.48 (1.14,1.92), and 2.18 (1.71,2.79). Models including the 273-variant genetic risk score plus lifestyle and clinical factors had a c-statistic of 0.67. In the general population, middle-aged adults in the highest quartile of either genetic risk score studied have approximately two-fold higher risk of an incident venous thromboembolism compared with the lowest quartile. The genetic risk scores show a weaker association with venous thromboembolism for Black people.

Social isolation and low social support are associated with low self-rated health (SRH) cross-sectionally, but few studies have assessed longitudinal associations. Assess the associations of isolation, support, and different types of support with SRH trajectories over 28 years. Examine 10-year changes in isolation and support and their associations with 18-year SRH trajectories. The Atherosclerosis Risk in Communities (ARIC) Study and the Jackson Heart Study (JHS) are population-based prospective cohort studies with some shared participants. We included 10,855 ARIC participants (56% women, 24% Black, mean age 57 (standard deviation: 6) years) with one measure of isolation and support in ARIC (1990-1992), and a subset of 911 ARIC/JHS shared cohort participants with these measures again in JHS (2000-2004). Isolation was measured using the 10-item Lubben Social Network Scale in ARIC, and with 3 questions from the Berkman Social Network Index in JHS. Support was measured using the 16-item Interpersonal Support Evaluation List in both studies. SRH was measured annually and scored from 0-100. We used linear mixed effects models adjusted for confounders to assess these associations. In ARIC, high isolation was associated with lower SRH both at baseline and over follow-up, with SRH decreasing at a slightly greater rate for those with high isolation compared to low. High support was associated with greater SRH over 28 years compared to those with low support, but the rate of decline in SRH was similar. On average, over 10 years, support was stable and isolation increased in ARIC/JHS. Although confidence intervals were wide, 10-year maintenance of high/moderate support and increases in support were associated with greater SRH over time compared to decreases in support and stable low support. Low isolation and high support at baseline and over 10 years may be positively associated with longitudinal SRH.

Most population-based estimates of incident hospitalized heart failure (HF) have not differentiated acute decompensated heart failure (ADHF) from chronic stable HF nor included racially diverse populations. The Atherosclerosis Risk in Communities Study conducted surveillance of hospitalized HF events (age ≥55 years) in 4 US communities. We estimated hospitalized ADHF incidence and survival by race and gender. Potential 2005 to 2009 HF hospitalizations were identified by International Classification of Diseases, Ninth Revision, Clinical Modification, codes; 6,168 records were reviewed to validate ADHF cases. Population estimates were derived from US Census data; 50% of eligible hospitalizations were classified as ADHF, of which 63.6% were incident ADHF and 36.4% were recurrent ADHF. The average incidence of hospitalized ADHF was 11.6 per 1,000 persons, aged ≥55 years, per year, and recurrent hospitalized ADHF was 6.6 per 1,000 persons/yr. Age-adjusted annual ADHF incidence was highest for black men (15.7 per 1,000), followed by black women (13.3 per 1,000), white men (12.3 per 1,000), and white women (9.9 per 1,000). Of incident ADHF events with heart function assessment (89%), 53% had reduced the ejection fraction (heart failure with reduced ejection fraction [HFrEF]) and 47% had preserved ejection fraction (heart failure with preserved ejection fraction [HFpEF]). Black men had the highest proportion of acute HFrEF events (70%); white women had the highest proportion of acute HFpEF (59%). Age-adjusted 28-day and 1-year case fatality after an incident ADHF was 10.4% and 29.5%, respectively. Survival did not differ by race or gender. In conclusion, ADHF hospitalization and HF type varied by both race and gender, but case fatality rates did not. Further studies are needed to explain why black men are at higher risk of hospitalized ADHF and HFrEF.

OBJECTIVE:-- To assess the magnitude of the association between the National Cholesterol Education Program's Third Adult Treatment Panel Report (ATP III) definition of the metabolic syndrome and cardiovascular disease (CVD). RESEARCH DESIGN AND METHODS-- Cox regression was used to estimate the relative risk of incident coronary heart disease (CHD) and stroke among 12,089 black and white middle-aged individuals in the Atherosclerosis Risk in Communities (ARIC) study. RESULTS:-- The metabolic syndrome was present in [approximately]23% of individuals without diabetes or prevalent CVD at baseline. Over an average of 11 years of follow-up, 879 incident CHD and 216 ischemic stroke events occurred. Among the components of the metabolic syndrome, elevated blood pressure and low levels of HDL cholesterol exhibited the strongest associations with CHD. Men and women with the metabolic syndrome were [approximately]1.5 and 2 times more likely to develop CHD than control subjects after adjustment for age, smoking, LDL cholesterol, and race/ARIC center (sex interaction P < 0.03). Similar associations were found between the metabolic syndrome and incident ischemic stroke. Comparison of receiver operating characteristic curves indicated that the metabolic syndrome did not materially improve CHD risk prediction beyond the level achieved by the Framingham Risk Score (FRS). CONCLUSIONS:-- Individuals without diabetes or CVD, but with the metabolic syndrome, were at increased risk for long-term cardiovascular outcomes, although statistical models suggested that most of that risk was accounted for by the FRS. Nevertheless, identification of individuals with the metabolic syndrome may provide opportunities to intervene earlier in the development of shared disease pathways that predispose individuals to both CVD and diabetes.

In the US, medication assisted treatment, particularly with office-based buprenorphine, has been an important component of opioid dependence treatment among patients with iatrogenic addiction to opioid analgesics. The predictors of initiating buprenorphine for addiction among opioid analgesic patients have not been well-described. We conducted a time-to-event analysis using data from the North Carolina (NC) Prescription Drug Monitoring Program (PDMP). Our outcome of interest was time-to-initiation of sublingual buprenorphine. Our study population was a prospective cohort of all state residents receiving a full-agonist opioid analgesic between 2011 and 2015. Predictors of initiation of sublingual buprenorphine examined included: age, gender, cumulative pharmacies and prescribers utilized, cumulative opioid intensity (defined as cumulative opioid exposure divided by duration of opioid exposure), and benzodiazepine dispensing. Of 4.3 million patients receiving opioid analgesics in NC between 2011 and 2015 (accumulated 8.30 million person-years of follow-up), and a total of 28,904 patients initiated buprenorphine formulations intended for addiction treatment (overall rate 3.48 per 1,000 person-years). In adjusted multivariate models, the utilization of 3 or more pharmacies (HR: 2.93; 95% CI: 2.82, 3.05) or 6 or more controlled substance prescribers (HR: 12.09; 95% CI: 10.76, 13.57) was associated with buprenorphine initiation. A dose-response relationship was observed for cumulative opioid intensity (HR in highest decile relative to lowest decile: 5.05; 95% CI: 4.70, 5.42). Benzodiazepine dispensing was negatively associated with buprenorphine initiation (HR: 0.63; 95% CI: 0.61, 0.65). Opioid analgesic patients utilizing multiple prescribers or pharmacies are more likely to initiate sublingual buprenorphine. This finding suggests that patients with multiple healthcare interactions are more likely to be treated for high-risk opioid use, or may be more likely to be identified and treated for addiction. Future research should utilize prescription monitoring program data linked to electronic health records to include diagnosis information in analytic models.

The metabolism of high-fructose corn syrup used to sweeten soda drinks may lead to elevations in uric acid levels. Here we determined whether soda drinking is associated with hyperuricemia and, as a potential consequence, reduced kidney function. At baseline, 15,745 patients in the Atherosclerosis Risk in Communities Study completed a dietary questionnaire and had measurements of their serum creatinine and uric acid. After 3 and 9 years of follow-up, multivariate odds ratios from logistic regressions for binary outcome of hyperuricemia and chronic kidney disease (eGFR less than 60 ml/min per 1.73 m2) were evaluated. Compared to participants who drank less, consumption of over one soda per day was associated with increased odds of prevalent hyperuricemia and chronic kidney disease. The odds ratio for chronic kidney disease significantly increased to 2.59 among participants who drank more than one soda per day and had a serum uric acid level over 9.0 mg/dl. In longitudinal analyses, however, drinking more than one soda per day was not associated with hyperuricemia or chronic kidney disease. Neither preexistent hyperuricemia nor development of hyperuricemia modified the lack of association between soda drinking and incident chronic kidney disease. Thus our study shows that high consumption of sugar-sweetened soda was associated with prevalent but not incident hyperuricemia and chronic kidney disease.

Anemia is associated with poor prognosis in patients hospitalized with acute decompensated heart failure (ADHF). Whether the impact of anemia differs by heart failure with preserved ejection fraction (HFpEF) or heart failure with reduced ejection fraction (HFrEF) is uncertain. We examined hospital surveillance data captured by the Atherosclerosis Risk in Communities Study from January 1, 2005, to December 31, 2010. Diagnoses of ADHF were validated by standardized physician review of the medical record. Anemia was classified using the World Health Organization criteria (<12 g/dl for women and <13 g/dl for men), and HF type was determined by the ejection fraction (<40% for HFrEF and ≥40% for HFpEF). Hospital length of stay and 1-year mortality outcomes were analyzed by multivariable regression, weighted to account for the sampling design, and adjusted for demographics and clinical covariates. Over 6 years, 15,461 (weighted) hospitalized events for ADHF (59% HFrEF) occurred in the catchment of the Atherosclerosis Risk in Communities, based on 3,309 sampled events. Anemia was associated with a mortality hazard ratio of 2.1 (95% confidence interval [CI] 1.6 to 2.7) in patients classified with HFpEF and 1.4 (95% CI 1.1 to 1.7) in those with HFrEF; p for interaction = 0.05. The mean increase in length of hospital stay associated with anemia was 3.5 days (95% CI 3.4 to 3.6) for patients with HFpEF, compared with 1.8 days (95% CI 1.7 to 1.9) for those with HFrEF; p for interaction <0.0001. In conclusion, the incremental risks of death and lengthened hospital stay associated with anemia are more pronounced in ADHF patients classified with HFpEF than HFrEF.

Experimental and observational research has suggested the potential for increased type 2 diabetes (T2D) risk among populations taking statins for the primary prevention of atherosclerotic cardiovascular disease (ASCVD). However, few studies have directly compared statin-associated benefits and harms or examined heterogeneity by population subgroups or assumed treatment effect. Thus, we compared ASCVD risk reduction and T2D incidence increases across 3 statin treatment guidelines or recommendations among adults without a history of ASCVD or T2D who were eligible for statin treatment initiation. Simulations were conducted using Markov models that integrated data from contemporary population-based studies of non-Hispanic African American and white adults aged 40-75 years with published meta-analyses. Statin treatment eligibility was determined by predicted 10-year ASCVD risk (5%, 7.5%, or 10%). We calculated the number needed to treat (NNT) to prevent one ASCVD event and the number needed to harm (NNH) to incur one incident case of T2D. The likelihood to be helped or harmed (LHH) was calculated as ratio of NNH to NNT. Heterogeneity in statin-associated benefit was examined by sex, age, and statin-associated T2D relative risk (RR) (range: 1.11-1.55). A total of 61,125,042 U.S. adults (58.5% female; 89.4% white; mean age = 54.7 years) composed our primary prevention population, among whom 13-28 million adults were eligible for statin initiation. Overall, the number of ASCVD events prevented was at least twice as large as the number of incident cases of T2D incurred (LHH range: 2.26-2.90). However, the number of T2D cases incurred surpassed the number of ASCVD events prevented when higher statin-associated T2D RRs were assumed (LHH range: 0.72-0.94). In addition, females (LHH range: 1.74-2.40) and adults aged 40-50 years (LHH range: 1.00-1.14) received lower absolute benefits of statin treatment compared with males (LHH range: 2.55-3.00) and adults aged 70-75 years (LHH range: 3.95-3.96). Projected differences in LHH by age and sex became more pronounced as statin-associated T2D RR increased, with a majority of scenarios projecting LHHs < 1 for females and adults aged 40-50 years. This study's primary limitation was uncertainty in estimates of statin-associated T2D risk, highlighting areas in which additional clinical and public health research is needed. Our projections suggest that females and younger adult populations shoulder the highest relative burden of statin-associated T2D risk.

Background Pragmatic randomized clinical trials are essential to determine the effectiveness of interventions in “real-world” clinical practice. These trials frequently use a cluster-randomized methodology, with randomization at the site level. Despite policymakers’ increased interest in supporting pragmatic randomized clinical trials, no studies to date have reported on the unique recruitment challenges faced by cluster-randomized pragmatic trials. We investigated key challenges and successful strategies for hospital recruitment in the Comprehensive Post-Acute Stroke Services (COMPASS) study. Methods The COMPASS study is designed to compare the effectiveness of the COMPASS model versus usual care in improving functional outcomes, reducing the numbers of hospital readmissions, and reducing caregiver strain for patients discharged home after stroke or transient ischemic attack. This model integrates early supported discharge planning with transitional care management, including nurse-led follow-up phone calls after 2, 30, and 60 days and an in-person clinic visit at 7–14 days involving a functional assessment and neurological examination. We present descriptive statistics of the characteristics of successfully recruited hospitals compared with all eligible hospitals, reasons for non-participation, and effective recruitment strategies. Results We successfully recruited 41 (43%) of 95 eligible North Carolina hospitals. Leading, non-exclusive reasons for non-participation included: insufficient staff or financial resources ( n  = 33, 61%), lack of health system support ( n  = 16, 30%), and lack of support of individual decision-makers ( n  = 11, 20%). Successful recruitment strategies included: building and nurturing relationships, engaging team members and community partners with a diverse skill mix, identifying gatekeepers, finding mutually beneficial solutions, having a central institutional review board, sharing published pilot data, and integrating contracts and review board administrators. Conclusions Although we incorporated strategies based on the best available evidence at the outset of the study, hospital recruitment required three times as much time and considerably more staff than anticipated. To reach our goal, we tailored strategies to individuals, hospitals, and health systems. Successful recruitment of a sufficient number and representative mix of hospitals requires considerable preparation, planning, and flexibility. Strategies presented here may assist future trial organizers in implementing cluster-randomized pragmatic trials. Trial registration Clinicaltrials.gov, NCT02588664 . Registered on 23 October 2015.