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Objectives Adiposity may have a role in the risk of dementia. Fewer studies have focused on the relationship between change in adiposity and cognitive decline. Our study aimed to explore the association between the change in adiposity and cognitive function in Black and White older adults. Methods The participants were 12,204 older adults without cognitive impairment (62.8 ± 8.0 years) in the United States. The percent body mass index change (%BMI change) and percent waist circumference change (%WC change) were measured at 2 in-home visits (first: 2003–2007, second: 2013–2016). Cognitive status was assessed by the Six-Item Screener annually. Memory and executive function were measured by word list learning, MOCA recall and orientation, and letter and animal fluency every 2 years. Logistic regression or linear regression models were used to estimate the relationship between percent change in adiposity and cognitive function. Results After 12.7 ± 1.7 years, a greater decrease in %BMI change or %WC change was significantly associated with a higher risk of cognitive impairment. Compared to older adults with −5% ≤ change ≤ 5% from baseline, a significantly higher risk of cognitive impairment and greater loss in memory and executive function were found among those who experienced more than a 10% decline in %BMI change or %WC change. Older adults who experienced a 5%–10% decrease in %BMI change had a higher risk of cognitive impairment and greater loss of memory compared to those with −5% ≤ change ≤ 5%. Discussion A greater decrease in %BMI (>5%) and %WC (>10%) change was associated with greater cognitive loss observed over time. [ABSTRACT FROM AUTHOR]

Objective: We examined whether relative availability of fast-food restaurants and supermarkets mediates the association between worse neighborhood socioeconomic conditions and risk of developing type 2 diabetes (T2D).Research Design and Methods: As part of the Diabetes Location, Environmental Attributes, and Disparities Network, three academic institutions used harmonized environmental data sources and analytic methods in three distinct study samples: 1) the Veterans Administration Diabetes Risk (VADR) cohort, a national administrative cohort of 4.1 million diabetes-free veterans developed using electronic health records (EHRs); 2) Reasons for Geographic and Racial Differences in Stroke (REGARDS), a longitudinal, epidemiologic cohort with Stroke Belt region oversampling (N = 11,208); and 3) Geisinger/Johns Hopkins University (G/JHU), an EHR-based, nested case-control study of 15,888 patients with new-onset T2D and of matched control participants in Pennsylvania. A census tract-level measure of neighborhood socioeconomic environment (NSEE) was developed as a community type-specific z-score sum. Baseline food-environment mediators included percentages of 1) fast-food restaurants and 2) food retail establishments that are supermarkets. Natural direct and indirect mediating effects were modeled; results were stratified across four community types: higher-density urban, lower-density urban, suburban/small town, and rural.Results: Across studies, worse NSEE was associated with higher T2D risk. In VADR, relative availability of fast-food restaurants and supermarkets was positively and negatively associated with T2D, respectively, whereas associations in REGARDS and G/JHU geographies were mixed. Mediation results suggested that little to none of the NSEE-diabetes associations were mediated through food-environment pathways.Conclusions: Worse neighborhood socioeconomic conditions were associated with higher T2D risk, yet associations are likely not mediated through food-environment pathways. [ABSTRACT FROM AUTHOR]

Context: The peptide neurotensin is implicated in insulin resistance, diabetes mellitus (DM), and cardiovascular disease.Objective: We studied the association of neurotensin's stable precursor, pro-neurotensin/neuromedin N (pro-NT/NMN) with incident metabolic syndrome (MetS) and DM.Methods: We included 3772 participants from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study who completed the baseline exam (2003-2007), the follow-up exam (2013-2016), and had pro-NT/NMN measured by immunoassay. Weighted logistic regression models were fitted to incident DM, incident MetS, and each MetS component, separately, incorporating demographics, metabolic risk factors, homeostasis model of insulin resistance (HOMA-IR), and diet scores. Incident MetS was defined by 3 or more harmonized criteria at follow-up in those with fewer than 3 at baseline. Incident DM was defined by use of hypoglycemic drugs/insulin, fasting glucose 126 mg/dL or greater, or random glucose 200 mg/dL or greater in those without these at baseline.Results: Median (IQR) plasma pro-NT/NMN was 160 pmol/L (118-218 pmol/L). A total of 564 (of 2770 without baseline MetS) participants developed MetS, and 407 (of 3030 without baseline DM) developed DM. Per SD higher log-pro-NT/NMN, the demographic-adjusted odds ratio (OR) and 95% CI of incident MetS was 1.22 (1.11-1.35), 1.16 (1.00-1.35) for incident low high-density lipoprotein (HDL), and 1.25 (1.11-1.40) for incident dysglycemia. The association of pro-NT/NMN with MetS was attenuated in the model adding HOMA-IR (OR per SD log-pro-NT/NMN 1.14; 95% CI, 1.00-1.30). There was no association with incident DM (OR per SD log-pro-NT/NMN 1.06; 95% CI, 0.94-1.19).Conclusion: Pro-NT/NMN was associated with MetS and 2 components, dysglycemia and low HDL, likely explained by insulin resistance. [ABSTRACT FROM AUTHOR]

Under covariate adaptive randomization, the covariate is tied to both randomization and analysis. Misclassification of such covariate will impact the intended treatment assignment; further, it is unclear what the appropriate analysis strategy should be. We explore the impact of such misclassification on the trial's statistical operating characteristics. Simulation scenarios were created based on the misclassification rate and the covariate effect on the outcome. Models including unadjusted, adjusted for the misclassified, or adjusted for the corrected covariate were compared using logistic regression for a binary outcome and Poisson regression for a count outcome. For the binary outcome using logistic regression, type I error can be maintained in the adjusted model, but the test is conservative using an unadjusted model. Power decreased with both increasing covariate effect on the outcome as well as the misclassification rate. Treatment effect estimates were biased towards the null for both the misclassified and unadjusted models. For the count outcome using a Poisson model, covariate misclassification led to inflated type I error probabilities and reduced power in the misclassified and the unadjusted model. The impact of covariate misclassification under covariate-adaptive randomization differs depending on the underlying distribution of the outcome. [ABSTRACT FROM AUTHOR]

Objective: To characterize cerebral microbleeds (CMBs) in lacunar stroke patients in the Secondary Prevention of Small Subcortical Strokes (SPS3) trial and to assess their relationship with recurrent stroke and death, and response to assigned treatment.Methods: SPS3 is a randomized, clinical trial conducted between 2003 and 2011. Patients with recent magnetic resonance imaging (MRI)-documented lacunar infarcts were randomly assigned in a factorial design to target levels of systolic blood pressure (130-149mmHg vs <130mmHg; open label) and to antiplatelet treatment (aspirin/clopidogrel vs aspirin/placebo; double-blinded). The current analysis involves 1,278 trial participants who had a baseline axial T2*-weighted gradient echo MRI sequence allowing for CMB detection.Results: CMBs were present in 30% of 1,278 patients (mean age = 63 years). Male gender (odds ratio [OR] = 1.7, 95% confidence interval [CI] = 1.3-2.3), history of hypertension (OR = 1.6, 95% CI = 1.2-2.3), increased systolic blood pressure (1.2 per 20mmHg, 95% CI = 1.1-1.4), nondiabetic status (OR = 1.4, 95% CI = 1.1-1.9), multiple old lacunar infarcts (OR = 1.9, 95% CI = 1.5-2.5), and moderate (OR = 1.7, 95% CI = 1.2-2.3) or severe (OR = 4.2, 95% CI = 3.0-5.9) white matter hyperintensities on MRI were independently associated with CMBs. During a mean follow-up of 3.3 years, overall stroke recurrence was 2.5% per patient-year. Patients with CMBs had an adjusted 2-fold increased risk of recurrent stroke (hazard ratio = 2.1, 95% CI = 1.4-3.1). CMBs were not a risk factor for death. There were no statistically significant interactions between CMBs and treatment assignments.Interpretation: Patients with lacunar stroke and CMBs likely harbor a more advanced form of cerebral small vessel disease in need of efficacious therapeutic strategies. Ann Neurol 2017;82:196-207. [ABSTRACT FROM AUTHOR]

Background: Hospitalization of patients with chronic obstructive pulmonary disease creates a huge healthcare burden. Positive airway pressure therapy is sometimes used in patients with chronic obstructive pulmonary disease, but the possible impact on hospitalization risk remains controversial. We studied the hospitalization risk of patients with chronic obstructive pulmonary disease before and after initiation of various positive airway pressure therapies in a "real-world" bioinformatics study.Methods: We performed a retrospective analysis of administrative claims data of hospitalizations in patients with chronic obstructive pulmonary disease who received or did not receive positive airway pressure therapy: continuous positive airway pressure, bilevel positive airway pressure, and noninvasive positive pressure ventilation using a home ventilator.Results: The majority of 1,881,652 patients with chronic obstructive pulmonary disease (92.5%) were not receiving any form of positive airway pressure therapy. Prescription of bilevel positive airway pressure (1.5%), continuous positive airway pressure (5.6%), and noninvasive positive pressure ventilation (<1%) in patients with chronic obstructive pulmonary disease demonstrated geographic-, sex-, and age-related variability. After adjusting for confounders and propensity score, noninvasive positive pressure ventilation (odds ratio [OR], 0.19; 95% confidence interval [CI], 0.13-0.27), bilevel positive airway pressure (OR, 0.42; 95% CI, 0.39-0.45), and continuous positive airway pressure (OR, 0.70; 95% CI, 0.67-0.72) were individually associated with lower hospitalization risk in the 6 months post-treatment when compared with the 6 months pretreatment but not when compared with the baseline period between 12 and 6 months before treatment initiation. Stratified analysis suggests that comorbid sleep-disordered breathing, chronic respiratory failure, heart failure, and age less than 65 years were associated with greater benefits from positive airway pressure therapy.Conclusion: Initiation of positive airway pressure therapy was associated with reduction in hospitalization among patients with chronic obstructive pulmonary disease, but the causality needs to be determined by randomized controlled trials. [ABSTRACT FROM AUTHOR]

Background: Geographic variations in cardiovascular mortality are substantial, but descriptions of geographic variations in major cardiovascular risk factors have relied on data aggregated to counties. Herein, we provide the first description of geographic variation in the prevalence of hypertension, diabetes mellitus, and smoking within and across US counties.Methods and Results: We conducted a cross-sectional analysis of baseline risk factor measurements and latitude/longitude of participant residence collected from 2003 to 2007 in the REGARDS study (Reasons for Geographic and Racial Differences in Stroke). Of the 30 239 participants, all risk factor measurements and location data were available for 28 887 (96%). The mean (±SD) age of these participants was 64.8(±9.4) years; 41% were black; 55% were female; 59% were hypertensive; 22% were diabetic; and 15% were current smokers. In logistic regression models stratified by race, the median(range) predicted prevalence of the risk factors were as follows: for hypertension, 49% (45%-58%) among whites and 72% (68%-78%) among blacks; for diabetes mellitus, 14% (10%-20%) among whites and 31% (28%-41%) among blacks; and for current smoking, 12% (7%-16%) among whites and 18% (11%-22%) among blacks. Hypertension was most prevalent in the central Southeast among whites, but in the west Southeast among blacks. Diabetes mellitus was most prevalent in the west and central Southeast among whites but in south Florida among blacks. Current smoking was most prevalent in the west Southeast and Midwest among whites and in the north among blacks.Conclusions: Geographic disparities in prevalent hypertension, diabetes mellitus, and smoking exist within states and within counties in the continental United States, and the patterns differ by race. [ABSTRACT FROM AUTHOR]

Objectives To describe the incidence of cardiovascular risk factors, or race-related disparities in incidence, across the age spectrum in adults. Design Longitudinal cohort. Setting National sample. Participants Community-dwelling black and white adults recruited between 2003 and 2007. Measurements Incident hypertension, diabetes mellitus, dyslipidemia and atrial fibrillation over 10 years of follow-up in 10,801 adults, stratified according to age (45-54, 55-64, 65-74, ≥75). Results There was no evidence ( P ≥ .68) of an age-related difference in the incidence of hypertension for white men (average incidence 38%), black men (48%), or black women (54%), although for white women incidence increased with age (45-54, 27%; ≥75, 40%). Incidence of diabetes mellitus was lower at older ages for white men (45-54, 15%; ≥75, 8%), black men (45-54, 29%; ≥75, 13%), and white women (45-54, 11%; ≥75, 4%), although there was no evidence ( P = .11) of age-related changes for black women (average incidence 21%). For dyslipidemia, incidence for all race-sex groups was approximately 20% for aged 45 to 54 but approximately 30% for aged 54 to 64 and 65 to 74 and approximately 22% for aged 75 and older. Incidence of atrial fibrillation was low at age 45 to 54 (<5%) but for aged 75 and older was approximately 20% for whites and 11% for blacks. The incidence of hypertension, diabetes mellitus, and dyslipidemia was higher in blacks across the age spectrum but lower for atrial fibrillation. Conclusion Incidence of risk factors remains high in older adults. Blacks have a higher incidence of hypertension, diabetes mellitus, and dyslipidemia after age 45, underscoring the ongoing importance of prevention of all three conditions in mid- to later life. [ABSTRACT FROM AUTHOR]

Background: Improved understanding of the etiology of cognitive impairment is needed to develop effective preventive interventions. Higher amino-terminal pro-B-type natriuretic peptide (NT-proBNP) is a biomarker of cardiac dysfunction associated with risk of cardiovascular diseases and stroke in apparently healthy people.Objective: To study the association of NT-proBNP with risk of incident cognitive impairment.Methods: The Reasons for Geographic and Racial Differences in Stroke is a national cohort study of 30,239 black and white Americans age 45 and older at baseline, enrolled in 2003-7. Among participants without prebaseline stroke or cognitive impairment, baseline NT-proBNP was measured in 470 cases of incident cognitive impairment and 557 controls. Cases were participants scoring below the 6th percentile of demographically-adjusted means on at least 2 of 3 serially administered tests (word list learning, word list recall and semantic fluency) over 3.5 years follow-up.Results: Adjusting for age, gender, race, region of residence, education, and income, there was an increased odds ratio of incident cognitive impairment with increasing NT-proBNP; participants in the 4th versus 1st quartile (>127 versus ≤33 pg/ml) had a 1.69-fold increased odds (95% CI 1.11-2.58). Adjustment for cardiovascular risk factors and presence of an apolipoprotein E4 allele had no substantial impact on the odds ratio. Results did not differ by age, race, gender, or presence of an apolipoprotein E4 allele.Conclusion: Higher NT-pro-BNP was associated with incident cognitive impairment in this prospective study, independent of atherogenic and Alzheimer's disease risk factors. Future work should clarify pathophysiologic connections of NT-proBNP and cognitive dysfunction. [ABSTRACT FROM AUTHOR]

Background/aims: The use of adaptive designs has been increasing in randomized clinical trials. Sample size re-estimation is a type of adaptation in which nuisance parameters are estimated at an interim point in the trial and the sample size re-computed based on these estimates. The Secondary Prevention of Small Subcortical Strokes study was a randomized clinical trial assessing the impact of single- versus dual-antiplatelet therapy and control of systolic blood pressure to a higher (130–149 mmHg) versus lower (<130 mmHg) target on recurrent stroke risk in a two-by-two factorial design. A sample size re-estimation was performed during the Secondary Prevention of Small Subcortical Strokes study resulting in an increase from the planned sample size of 2500–3020, and we sought to determine the impact of the sample size re-estimation on the study results. Methods: We assessed the results of the primary efficacy and safety analyses with the full 3020 patients and compared them to the results that would have been observed had randomization ended with 2500 patients. The primary efficacy outcome considered was recurrent stroke, and the primary safety outcomes were major bleeds and death. We computed incidence rates for the efficacy and safety outcomes and used Cox proportional hazards models to examine the hazard ratios for each of the two treatment interventions (i.e. the antiplatelet and blood pressure interventions). Results: In the antiplatelet intervention, the hazard ratio was not materially modified by increasing the sample size, nor did the conclusions regarding the efficacy of mono versus dual-therapy change: there was no difference in the effect of dual- versus monotherapy on the risk of recurrent stroke hazard ratios (n = 3020 HR (95% confidence interval): 0.92 (0.72, 1.2), p = 0.48; n = 2500 HR (95% confidence interval): 1.0 (0.78, 1.3), p = 0.85). With respect to the blood pressure intervention, increasing the sample size resulted in less certainty in the results, as the hazard ratio for higher versus lower systolic blood pressure target approached, but did not achieve, statistical significance with the larger sample (n = 3020 HR (95% confidence interval): 0.81 (0.63, 1.0), p = 0.089; n = 2500 HR (95% confidence interval): 0.89 (0.68, 1.17), p = 0.40). The results from the safety analyses were similar to 3020 and 2500 patients for both study interventions. Other trial-related factors, such as contracts, finances, and study management, were impacted as well. Conclusion: Adaptive designs can have benefits in randomized clinical trials, but do not always result in significant findings. The impact of adaptive designs should be measured in terms of both trial results, as well as practical issues related to trial management. More post hoc analyses of study adaptations will lead to better understanding of the balance between the benefits and the costs. [ABSTRACT FROM AUTHOR]

Aims: To determine if the association between electrocardiographic left ventricular hypertrophy (ECG-LVH) and ischaemic stroke is partially explained by the concomitant presence of QT prolongation.Methods and Results: A total of 24 948 (mean age = 65 ± 9.4 years; 40% black; 55% women) participants from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study were included in this analysis. Electrocardiographic left ventricular hypertrophy was defined by the Sokolow-Lyon criteria. Heart rate-adjusted QT (QTa) was computed using a linear regression model. Adjudicated ischaemic stroke events were the outcome of interest. Cox regression was used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between ECG-LVH and prolonged QTa, in isolation and combined, with ischaemic stroke. There were 2422 (9.7%) participants with ECG-LVH, 820 (3.3%) with prolonged QTa, and 161 (0.6%) with both. Over a median follow-up of 7.6 years, 714 (2.9%) ischaemic stroke events occurred. After adjustment for stroke risk factors and potential confounders, an increased risk of ischaemic stroke was observed among participants with ECG-LVH and prolonged QTa (HR = 1.85, 95% CI = 1.04-3.30), isolated ECG-LVH (HR = 1.40, 95% CI = 1.13-1.75), and isolated prolonged QTa (HR = 1.45, 95% CI = 1.04-2.03) compared with participants without either condition. When ECG-LVH and prolonged QTa were examined as separate variables, the risk of ischaemic stroke for each condition remained statistically significant.Conclusion: The combination of ECG-LVH and prolonged QT is associated with a higher risk of ischaemic stroke compared with either condition in isolation, and the stroke risk for each condition does not depend on the presence of the other. [ABSTRACT FROM AUTHOR]

Background: The effect of intensive blood pressure (BP) lowering on kidney function among individuals with established cerebrovascular disease and preserved estimated glomerular filtration rate (eGFR) is not established. Methods and Results: Among 2610 participants randomized to a lower (<130 mm Hg) versus higher (130-149 mm Hg) systolic BP target with repeated measures of serum creatinine, we evaluated differences by study arm in annualized eGFR decline and rapid decline (eGFR decline >30%) using linear mixed models and logistic regression, respectively. We assessed associations of both treatment and kidney function decline with stroke, major vascular events, and the composite of stroke, death, major vascular events, or myocardial infarction using multivariable Cox regression, separately and jointly including a test for interaction. Analyses were conducted by treatment arm. Mean age was 63±11 years; 949 participants (36%) were diabetic; and mean eGFR was 80±19 mL·min(-1)·1.73 m(-2). At 9 months, achieved systolic BP was 137±15 versus 127±14 mm Hg in the higher versus lower BP group, and differences were maintained throughout follow-up (mean, 3.2 years). Compared with the higher target, the lower BP target had a -0.50-mL·min(-1)·1.73 m(-2) per year (95% confidence interval [CI], -0.79 to -0.21) faster eGFR decline. Differences were most pronounced during the first year (-2.1 mL·min(-1)·1.73 m(-2); 95% CI, -0.97 to -3.2), whereas rates of eGFR decline did not differ after year 1 (-0.095; 95% CI, -0.47 to 0.23). A total of 313 patients (24%) in the lower BP group had rapid kidney function decline compared with 247 (19%) in the higher BP group (odds ratio, 1.4; 95% CI, 1.1-1.6). Differences in rapid decline by treatment arm were apparent in the first year (odds ratio, 1.4; 95% CI, 1.1-1.8) but were not significant after year 1 (odds ratio, 1.0; 95% CI, 0.73-1.4). Rapid decline was associated with higher risk for stroke, major vascular events, and composite after full adjustment among individuals randomized to the higher BP target (stroke hazard ratio, 1.93; 95% CI, 1.15-3.21) but not the lower BP arm (stroke hazard ratio, 0.93; 95% CI, 0.50-1.75; all P for interaction <0.06). Conclusions: In patients with prior lacunar stroke and relatively preserved kidney function, intensive BP lowering was associated with a greater likelihood of rapid kidney function decline. Differences were observed primarily during the first year of antihypertensive treatment. Rapid kidney function decline was not associated with increased risk for clinical events among those undergoing intensive BP lowering. Clinical Trial Registration: URL: http://www.clinicalTrials.gov. Unique identifier: NCT00059306. [ABSTRACT FROM AUTHOR]

Background: Noncompliance to treatment assignment is an inevitable occurrence in randomized clinical trials (RCTs). Intention to treat (ITT) is generally considered the best method for addressing noncompliance in RCTs. Alternatives to ITT exist, including per protocol (PP), as treated (AT), and instrumental variables (IV). These three methods define participant compliance dichotomously, but partial compliance is a common occurrence in RCTs. By defining a threshold, above which a participant is called a complier, PP, AT and IV can be used, but the resulting loss of information may affect their performance. Trials with factorial designs may experience higher rates of noncompliance due to the heavier burden that participants experience by being assigned to multiple experimental treatments.Methods: Using simulations, we assessed the performance of ITT, PP, AT, and IV in both the partial compliance setting and in a 2-by-2 factorial design with increased participant burden for those randomized to both active treatments.Results: The bias, mean squared error, and type I error rates of the IV method after dichotomizing partial compliance were heavily inflated. The performance of all four methods depended on the level of noncompliance present, with higher average noncompliance leading to poorer performance. PP and AT showed improved bias and power relative to ITT without inflating the type I error beyond acceptable limits. However, the PP and AT heavily inflated the type I error rates when participant compliance was affected by the participants' general health.Conclusions: There are consequences for dichotomizing compliance information to make it fit into well-known methods. The results suggest the need for a method of estimating treatment effects that can utilize partial compliance information. [ABSTRACT FROM AUTHOR]

Objectives. We e va luated th e e ffe c t o f n e ig h b o rh o o d d isa d van ta g e (ND) on o ld e r a d u lts ' prevalence, awareness, tre a tm e n t, and c o n tro l o f h yp e rte n s io n . Methods. Data w e re from th e U n iv e rs ity o f A la b am a at B irm in g h am S tu d y o f A g in g , an o b s e rv a tio n a l s tu d y o f 1000 c om m u n ity -dw e llin g Black and W h ite A la b am ia n s aged 65 years and o ld e r, in 1999 to 2001. We assessed h yp e rte n s io n prevalence, awareness, tre a tm e n t, and c o n tro l w ith b lo o d pressure measurem e n ts and se lf-re p o rt data. We assessed ND w ith US Census data c o rre s p o n d in g w ith participants' census tracts, created tertiles o f ND, and fit models w ith generalized estimating equations via a lo g it link function w ith a binomial distribution. Adjusted models included variables assessing personal advantage and disadvantage, placebased factors, sociodemographics, comorbidities, and health behaviors. Results. L iv in g in m id -N D (adjusted o dds ra tio [AOR] = 1.6; 95% co n fid e n ce in te rva l [Cl] = 1.2, 2.1) and h ig h -N D te rtile s (AOR = 1.8; 95% Cl = 1.3, 2.3) was associated w ith h ig h e r hype rte n s io n prevalence, and liv in g in high-ND te rtile s w as associated w ith low e r o dds o f co n tro lle d h yp ertens ion (AOR = 0.6; 95% Cl = 0.4, 0.6). In adjusted models, ND was n o t associated w ith h yp ertens ion awareness o r tre a tm e n t. Conclusions. These fin d in g s s h ow th a t n e ig h b o rh o o d e n v iro nm e n ta l fa c to rs matter for hypertension outcomes and suggest the importance of ND for hypertension management in older adults. [ABSTRACT FROM AUTHOR]

Background: A deeper understanding of how heat wave definition affects the relationship between heat exposure and health, especially as a function of rurality, will be useful in developing effective heat wave warning systems. Objective: We compared the relationships between different heat wave index (HI) definitions and preterm birth (PTB) and nonaccidental death (NAD) across urban and rural areas. Methods: We used a time-stratified case-crossover design to estimate associations of PTB and NAD with heat wave days (defined using 15 HIs) relative to non-heat wave control days in Alabama, USA (1990-2010). ZIP code-level HIs were derived using data from the North American Land Data Assimilation System. Associations with heat wave days defined using different HIs were compared by bootstrapping. We also examined interactions with rurality. Results: Associations varied depending on the HI used to define heat wave days. Heat waves defined as having at least 2 consecutive days with mean daily temperatures above the 98th percentile were associated with 32.4% (95% CI: 3.7, 69.1%) higher PTB, and heat waves defined as at least 2 consecutive days with mean daily temperatures above the 90th percentile were associated with 3.7% (95% CI: 1.1, 6.3%) higher NAD. Results suggest that significant positive associations were more common when relative-compared with absolute-HIs were used to define exposure. Both positive and negative associations were found in each rurality stratum. However, all stratum-specific significant associations were positive, and NAD associations with heat waves were consistently positive in urban strata but not in middle or rural strata. Conclusions: Based on our findings, we conclude that a relative mean-temperature-only heat wave definition may be the most effective metric for heat wave warning systems in Alabama. [ABSTRACT FROM AUTHOR]

Longitudinal cohort studies normally identify and adjudicate incident events detected during follow-up by retrieving medical records. There are several reasons why the adjudication process may not be successfully completed for a suspected event including the inability to retrieve medical records from hospitals and an insufficient time between the suspected event and data analysis. These “incomplete adjudications” are normally assumed not to be events, an approach which may be associated with loss of precision and introduction of bias. In this article, the authors evaluate the use of multiple imputation methods designed to include incomplete adjudications in analysis. Using data from the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study, 2008−2009, they demonstrate that this approach may increase precision and reduce bias in estimates of the relations between risk factors and incident events. [ABSTRACT FROM PUBLISHER]

Background: Undertreatment of osteoporosis has been recognized as a common problem in selected patient subgroups. However, primary prevention has been hampered by limited risk assessment tools that can be applied to large populations.Objectives: Using clinical risk factors with a new tool from the World Health Organization (FRAX) and recommendations from the National Osteoporosis Foundation (NOF), we evaluated fracture risk and osteoporosis treatment in a US cohort.Participants: African Americans and Caucasians recruited from 2003-7 across the US as part of a longitudinal study.Design: Cross-sectional.Measures: The number of persons receiving prescription osteoporosis medications was assessed by race, sex, and fracture risk. Multivariable logistic regression evaluated the association between receipt of osteoporosis medications and fracture risk after controlling for potential confounders.Results: Among 24,783 participants, estimated fracture risk was highest for Caucasian women. After multivariable adjustment for fracture-related risk factors, the likelihood of receipt of osteoporosis medications among African Americans was lower than among Caucasians [odds ratio (OR) = 0.44, 95% confidence interval (CI) 0.37, 0.53] and for men compared to women (OR = 0.08, 95% CI 0.06-0.10). Even for the highest risk group, Caucasian women with 10-year hip fracture risk > or = 3% (n = 3,025, 39.7%), only 26% were receiving treatment.Conclusions: A substantial gap exists between 2008 NOF treatment guidelines based on fracture risk and the receipt of prescription osteoporosis medications. This gap was particularly notable for African Americans and men. FRAX is likely to be useful to assess risk at a population level and identify high-risk persons in need of additional evaluation. [ABSTRACT FROM AUTHOR]

Background: Despite concerns about adverse neurocognitive events raised by prior trials, pharmacological PCSK9 (proprotein convertase subtilisin/kexin type-9) inhibition was not associated with neurocognitive effects in a recent phase 3 randomized trial. PCSK9 loss-of-function (LOF) variants that result in lifelong exposure to lower levels of low-density lipoprotein cholesterol can provide information on the potential long-term effects of lower low-density lipoprotein cholesterol on neurocognitive impairment and decline.Methods: We investigated the association between PCSK9 LOF variants and neurocognitive impairment and decline among black REGARDS study (Reasons for Geographic and Racial Differences in Stroke) participants with (n=241) and without (n=10 454) C697X or Y142X LOF variants. Neurocognitive tests included the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) battery (Word List Learning, World List Delayed Recall, Semantic Animal Fluency) and Six-Item Screener (SIS) assessments, administered longitudinally during follow-up. Neurocognitive impairment was defined as a score ≥1.5 SD below age, sex, and education-based stratum-specific means on 2 or 3 CERAD assessments or, separately, a score <5 on any SIS assessment at baseline or during follow-up. Neurocognitive decline was assessed using standardized continuous scores on individual neurocognitive tests.Results: The mean sample age was 64 years (SD, 9), 62% were women, and the prevalence of neurocognitive impairment at any assessment was 6.3% by CERAD and 15.4% by SIS definitions. Adjusted odds ratios for neurocognitive impairment for participants with versus without PCSK9 LOF variants were 1.11 (95% confidence interval [CI], 0.58-2.13) using the CERAD battery and 0.89 (95% CI, 0.61-1.30) using the SIS assessment. Standardized average differences in individual neurocognitive assessment scores over the 5.6-year (range, 0.1-9.1) study period ranged between 0.07 (95% CI, -0.06 to 0.20) and -0.07 (95% CI, -0.18 to 0.05) among participants with versus without PCSK9 LOF variants. Patterns of neurocognitive decline were similar between participants with and without PCSK9 LOF variants (all P>0.10). Odds ratios for neurocognitive impairment per 20 mg/dL low-density lipoprotein cholesterol decrements were 1.02 (95% CI, 0.96-1.08) and 0.99 (95% CI, 0.95-1.02) for the CERAD and SIS definitions of impairment, respectively.Conclusions: These results suggest that lifelong exposure to low PCSK9 levels and cumulative exposure to lower levels of low-density lipoprotein cholesterol are not associated with neurocognitive effects in blacks. [ABSTRACT FROM AUTHOR]

Introduction: Stroke is a major public health concern worldwide given the associated morbidity and mortality. Smoking is a risk factor for stroke, but the relationship between secondhand smoke (SHS) exposure and stroke has been inconsistent to date. The aim of the current study was to examine the association of SHS exposure and risk of stroke and its subtypes (ischemic and hemorrhagic stroke) among nonsmokers.Methods: Demographic and clinical characteristics were compared by SHS exposure status for African American and white nonsmokers aged ≥45 years in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study in 2014. Hazard ratios (HRs) and corresponding 95% CIs were calculated by Cox proportional hazards models to assess the relationship between SHS exposure and stroke risk.Results: Of the 21,743 participants (38% African American, 45% male), SHS exposure in the past year was reported by 23%. Compared with those without SHS exposure, exposed participants were more likely to be female, white, younger, and reside with a smoker (all p<0.001). A total of 428 incident strokes were observed from April 2003 to March 2012 during a mean follow-up of 5.6 years. The risk of overall stroke was increased 30% among those with SHS exposure after adjustment for other stroke risk factors (95% CI=2%, 67%). This relationship appeared to be driven by ischemic strokes.Conclusions: SHS exposure is independently associated with an increased risk of stroke. Future studies are needed to confirm these findings and examine the role of long-term effects of SHS exposure on stroke outcomes. [ABSTRACT FROM AUTHOR]