The Association between Type of Insurance Plan, Out-of-Pocket Cost, and Adherence to Antihypertensive Medications in Medicare Supplement Insurance Enrollees.

BACKGROUND: Medicare supplement insurance, or Medigap, covers 21% of Medicare beneficiaries. Despite offsetting some out-of-pocket (OOP) expenses, remaining OOP costs may pose a barrier to medication adherence. This study aims to evaluate how OOP costs and insurance plan types influence medication adherence among beneficiaries covered by Medicare Supplement plans. METHODS: We conducted a retrospective analysis of the MerativeTM MarketScan® Medicare Supplement Database (2017-2019) in Medigap enrollees (≥ 65 years) with hypertension. Proportion of days covered (PDC) was a continuous measure of medication adherence and was also dichotomized (PDC ≥ 0.8) to quantify adequate adherence. Beta-binomial and logistic regression models were used to estimate associations between these outcomes and insurance plan type and log-transformed OOP costs, adjusting for patient characteristics. RESULTS: Among 27,407 patients with hypertension, the average PDC was 0.68 ± 0.31; 47.5% achieved adequate adherence. A mean $1 higher in 30-day OOP costs was associated with a 0.06 (95% Confidence intervals [CI]: -0.09 - -0.03) lower probability of adequate adherence, or a 5% (95% C.I.: 4% - 7%) decrease in PDC. Compared to comprehensive plan enrollees, the odds of adequate adherence were lower among those with point-of-service plans (O.R.: 0.69, 95%C.I.: 0.62 - 0.77), but higher among those with preferred provider organization (PPO) plans (O.R.: 1.08, 95%C.I.: 1.01 - 1.15). Moreover, the association between OOP costs and PDC was significantly greater for PPO enrollees. CONCLUSIONS: While Medicare supplement insurance alleviates some OOP costs, different insurance plans and remaining OOP costs influence medication adherence. Reducing patient cost-sharing may improve medication adherence.

Identifying a group of factors predicting cognitive impairment among older adults.

BACKGROUND: Cognitive impairment has multiple risk factors spanning several domains, but few studies have evaluated risk factor clusters. We aimed to identify naturally occurring clusters of risk factors of poor cognition among middle-aged and older adults and evaluate associations between measures of cognition and these risk factor clusters. METHODS: We used data from the National Health and Nutrition Examination Survey (NHANES) III (training dataset, n = 4074) and the NHANES 2011-2014 (validation dataset, n = 2510). Risk factors were selected based on the literature. We used both traditional logistic models and support vector machine methods to construct a composite score of risk factor clusters. We evaluated associations between the risk score and cognitive performance using the logistic model by estimating odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Using the training dataset, we developed a composite risk score that predicted undiagnosed cognitive decline based on ten selected predictive risk factors including age, waist circumference, healthy eating index, race, education, income, physical activity, diabetes, hypercholesterolemia, and annual visit to dentist. The risk score was significantly associated with poor cognitive performance both in the training dataset (OR Tertile 3 verse tertile 1 = 8.15, 95% CI: 5.36-12.4) and validation dataset (OR Tertile 3 verse tertile 1 = 4.31, 95% CI: 2.62-7.08). The area under the receiver operating characteristics curve for the predictive model was 0.74 and 0.77 for crude model and model adjusted for age, sex, and race. CONCLUSION: The model based on selected risk factors may be used to identify high risk individuals with cognitive impairment.

Serum soluble alpha-klotho klotho and cognitive functioning in older adults aged 60 and 79: an analysis of cross-sectional data of the National Health and Nutrition Examination Survey 2011 to 2014.

OBJECTIVES: Klotho, consisting of membrane klotho and soluble alpha-klotho, is found to be associated with better cognitive outcomes in small samples of the aged population. We aimed to examine the association of serum soluble alpha-klotho with cognitive functioning among older adults using a nationally representative sample of U.S. older adults. METHOD: A total of 2,173 U.S. older adults aged 60-79 years in the National Health and Nutrition Examination Survey from 2011 to 2014 were included in this cross-sectional analysis. Serum soluble alpha-klotho was measured in the laboratory and analyzed with an ELISA kit. Cognitive function was measured using the Consortium to Establish a Registry for Alzheimer's Disease Word Learning subtest (CERAD-WL) immediate and delayed memory, the Animal fluency test (AFT), and the Digit Symbol Substitution Test (DSST). Test-specific and global cognition z-scores were calculated based on sample means and standard deviations. Multivariable linear regression models were applied to examine the association of quartiles and continuous value of serum soluble alpha-klotho with test-specific and global cognition z-scores. Subgroup analysis was conducted by sex. The following covariates were included in the analysis- age, sex, race/ethnicity, education, depressive symptoms, smoking status, body mass index (BMI), physical activity, stroke, prevalent coronary heart disease, total cholesterol, and systolic blood pressure. All the information was self-reported or obtained from health exams. RESULTS: Serum soluble alpha-klotho level in the lowest quartile was associated with lower z-scores for DSST (beta [ß] =-0.13, 95% confidence interval [CI]: -0.25, -0.01). For subgroup analysis, serum soluble alpha-klotho level in the lowest quartile was associated with lower z-scores for DSST (ß=-0.16, 95% CI: -0.32, -0.003) and global cognition (ß=-0.14, 95% CI: -0.28, -0.01) among female participants. No association was found between continuous serum soluble alpha-klotho and cognitive functioning among the participants. CONCLUSIONS: Lower serum soluble alpha-klotho quartile was associated with poorer cognitive functioning among older women. Future studies are expected to examine the longitudinal association between klotho levels and cognitive outcomes.

Central arterial stiffening and intracranial atherosclerosis: the atherosclerosis risk in communities neurocognitive study (ARIC-NCS): Aortic stiffness & intracranial atherosclerosis.

OBJECTIVES: Previous studies suggest an association between central arterial stiffness (CAS) and intracranial atherosclerotic disease (ICAD) among Asian participants with stroke or hypertension; this association has not been evaluated in United States populations. We assessed the cross-sectional association of CAS with ICAD presence and burden in late-life, and differences in association by age, sex, and race. MATERIALS AND METHODS: We conducted a cross-sectional analysis of 1,285 Atherosclerosis Risk in Communities Study participants [mean age 75 (standard deviation: 5) years, 38 % male, 20  % Black] at Visit 5 (2011-2013). CAS was measured as carotid-femoral pulse wave velocity (cfPWV) using the Omron VP-1000 Plus. ICAD was assessed using high-resolution vessel wall MRI and MR angiography. We evaluated associations of a 1 standard deviation (SD) cfPWV (3.02 m/s) and high vs. non-high cfPWV (≥ 13.57 m/s vs. < 13.57 m/s) with presence of plaques (yes/no) and plaque number (0, 1-2, and >2) using multivariable logistic and ordinal logistic regression models adjusted for covariates. RESULTS: Each one SD greater cfPWV was associated with higher odds of plaque presence (odds ratio (OR)=1.32, 95 % confidence interval (CI): 1.22, 1.43), and an incrementally higher odds of number of plaques (OR 1-2 vs. 0 plaques = 1.21, 95 % CI: 1.10, 1.33; OR >2 vs. 0 plaques = 1.51, 95 % CI: 1.33,1.71). Results suggested differences by race, with greater magnitude associations among Black participants. CONCLUSIONS: CAS was positively associated with ICAD presence and burden; cfPWV may be a useful subclinical vascular measure for identification of individuals who are at high risk for cerebrovascular disease.

Hearing Loss Prevalence, Years Lived With Disability, and Hearing Aid Use in the United States From 1990 to 2019: Findings From the Global Burden of Disease Study.

OBJECTIVES: This article describes key data sources and methods used to estimate hearing loss in the United States, in the Global Burden of Disease study. Then, trends in hearing loss are described for 2019, including temporal trends from 1990 to 2019, changing prevalence over age, severity patterns, and utilization of hearing aids. DESIGN: We utilized population-representative surveys from the United States to estimate hearing loss prevalence for the Global Burden of Disease study. A key input data source in modeled estimates are the National Health and Nutrition Examination Surveys (NHANES), years 1988 to 2010. We ran hierarchical severity-specific models to estimate hearing loss prevalence. We then scaled severity-specific models to sum to total hearing impairment prevalence, adjusted estimates for hearing aid coverage, and split estimates by etiology and tinnitus status. We computed years lived with disability (YLDs), which quantifies the amount of health loss associated with a condition depending on severity and creates a common metric to compare the burden of disparate diseases. This was done by multiplying the prevalence of severity-specific hearing loss by corresponding disability weights, with additional weighting for tinnitus comorbidity. RESULTS: An estimated 72.88 million (95% uncertainty interval (UI) 68.53 to 77.30) people in the United States had hearing loss in 2019, accounting for 22.2% (20.9 to 23.6) of the total population. Hearing loss was responsible for 2.24 million (1.56 to 3.11) YLDs (3.6% (2.8 to 4.7) of total US YLDs). Age-standardized prevalence was higher in males (17.7% [16.7 to 18.8]) compared with females (11.9%, [11.2 to 12.5]). While most cases of hearing loss were mild (64.3%, 95% UI 61.0 to 67.6), disability was concentrated in cases that were moderate or more severe. The all-age prevalence of hearing loss in the United States was 28.1% (25.7 to 30.8) higher in 2019 than in 1990, despite stable age-standardized prevalence. An estimated 9.7% (8.6 to 11.0) of individuals with mild to profound hearing loss utilized a hearing aid, while 32.5% (31.9 to 33.2) of individuals with hearing loss experienced tinnitus. Occupational noise exposure was responsible for 11.2% (10.2 to 12.4) of hearing loss YLDs. CONCLUSIONS: Results indicate large burden of hearing loss in the United States, with an estimated 1 in 5 people experiencing this condition. While many cases of hearing loss in the United States were mild, growing prevalence, low usage of hearing aids, and aging populations indicate the rising impact of this condition in future years and the increasing importance of domestic access to hearing healthcare services. Large-scale audiometric surveys such as NHANES are needed to regularly assess hearing loss burden and access to healthcare, improving our understanding of who is impacted by hearing loss and what groups are most amenable to intervention.

Longitudinal Associations of Diet, Food Insecurity, and Supplemental Nutrition Assistance Program Use with Global Cognitive Performance in Middle-Aged and Older Adults.

BACKGROUND: Diet quality, food access, and food assistance policies may be key modifiable factors related to cognitive decline. OBJECTIVE: We aimed to evaluate whether diet quality, food insecurity, and Supplemental Nutrition Assistance Program (SNAP) use are associated with longitudinal changes in cognition among older adults in the United States. METHODS: Food intake data from the Health Care and Nutrition Study were linked with longitudinal health information from 5 waves of the Health and Retirement Study (2012-2020). The analytic sample (n = 6968) included community-dwelling United States adults aged ≥51 y without cognitive impairment. Global cognition was measured using a telephone-based cognitive status interview (range: 0-27). Diet quality was measured with the Healthy Eating Index, using participants' average intake of 13 dietary components. Questions regarding food access and affordability were used to determine food insecurity and use of SNAP benefits. Linear mixed-effects regression models were used to estimate longitudinal associations between diet-related factors and cognitive score changes. RESULTS: Poorer diets [ß: -0.24; 95% confidence interval (CI): -0.33, -0.15], food insecurity (ß: -1.08; 95% CI: -1.31, -0.85), and SNAP use (ß: -0.57; 95% CI: -0.82, -0.32) were associated with lower baseline cognitive scores. Poorer diets (ß: -0.17; 95% CI: -0.29, -0.05) and food insecurity (ß: -0.23; 95% CI: -0.47, -0.01) were associated with significantly steeper declines in cognitive scores over time, after 8 and 2 y of follow-up, respectively; however, SNAP use was not significantly associated with the rate of cognitive decline over time. Estimates were qualitatively similar when restricting the sample to participants aged ≥65 y. CONCLUSIONS: Results suggest that food access and adherence to healthy diet recommendations may be important elements to maintain cognitive health in aging. SNAP benefits may be insufficient to prevent negative cognitive effects of poor diet and limited access to nutritious foods.

Initiation of Antihypertensive Medication from Midlife on Incident Dementia: The Health and Retirement Study.

BACKGROUND: Hypertension has been identified as a risk factor of dementia, but most randomized trials did not show efficacy in reducing the risk of dementia. Midlife hypertension may be a target for intervention, but it is infeasible to conduct a trial initiating antihypertensive medication from midlife till dementia occurs late life. OBJECTIVE: We aimed to emulate a target trial to estimate the effectiveness of initiating antihypertensive medication from midlife on reducing incident dementia using observational data. METHODS: The Health and Retirement Study from 1996 to 2018 was used to emulate a target trial among non-institutional dementia-free subjects aged 45 to 65 years. Dementia status was determined using algorithm based on cognitive tests. Individuals were assigned to initiating antihypertensive medication or not, based on the self-reported use of antihypertensive medication at baseline in 1996. Observational analog of intention-to-treat and per-protocol effects were conducted. Pooled logistic regression models with inverse-probability of treatment and censoring weighting using logistic regression models were applied, and risk ratios (RRs) were calculated, with 200 bootstrapping conducted for the 95% confidence intervals (CIs). RESULTS: A total of 2,375 subjects were included in the analysis. After 22 years of follow-up, initiating antihypertensive medication reduced incident dementia by 22% (RR = 0.78, 95% CI: 0.63, 0.99). No significant reduction of incident dementia was observed with sustained use of antihypertensive medication. CONCLUSION: Initiating antihypertensive medication from midlife may be beneficial for reducing incident dementia in late life. Future studies are warranted to estimate the effectiveness using large samples with improved clinical measurements.

Meta-Analysis of Variations in Association between APOE ɛ4 and Alzheimer's Disease and Related Dementias Across Hispanic Regions of Origin.

BACKGROUND: Emerging research has shown racial and ethnic variations in the magnitude of association between the apolipoprotein ɛ4 (APOE ɛ4) allele and the risk of developing Alzheimer's disease and related dementias (ADRD). Studies researching this association among Hispanic groups within and outside of the United States have produced inconsistent results. OBJECTIVE: To examine the association between the APOE ɛ4 allele and the risk of developing ADRD in global Hispanic populations from different ethnic regions of origin. METHODS: PubMed, Embase, Scopus, and PsycInfo were searched for studies relating to Hispanic/Latin American origin, APOE ɛ4, and ADRD. Odds ratios (OR) of ADRD risk for individuals with APOE ɛ4 versus those without APOE ɛ4 were extracted and calculated using random effects analysis. RESULTS: 20 eligible studies represented Caribbean Hispanic, Mexican, South American, Spanish, and Cuban groups. Overall, APOE ɛ4 was significantly associated with increased risk of ADRD (Odds Ratio [OR] 3.80, 95% CI: 2.38-6.07). The association was only significant in the South American (OR: 4.61, 95% CI: 2.74-7.75) subgroup. CONCLUSION: There was an association between APOE ɛ4 and increased ADRD risk for the South American subgroup. The strength of this association varied across Hispanic subgroups. Data is limited with more studies especially needed for adjusted analysis on Spanish, Central American, Cuban Hispanic, and Caribbean Hispanic groups. Results suggest additional environmental or genetic risk factors are associated with ethnic variations.

Ten-Year Cardiovascular Disease Risk Score and Cognitive Function Among Older Adults: The National Health and Nutrition Examination Survey 2011 to 2014.

Background The Framingham 10-year cardiovascular disease risk score, which is based on age, sex, smoking, total cholesterol, high-density lipoprotein-cholesterol, blood pressure, and diabetes, has been found to be associated with cognitive health, but these findings have not been validated in a representative sample in the United States. We aimed to examine the associations of Framingham risk score with cognitive function among older adults in a nationally representative sample, as well as by race or ethnicity, education, and family income. Methods and Results A total of 2254 older adults ≥60 years (57% female, 79% non-Hispanic White) in the National Health and Nutrition Examination Survey 2011 to 2014 were included in the final sample for analysis. All components of the Framingham risk score were obtained with questionnaire or measured in the laboratory. Cognitive function was examined using the Consortium to Establish a Registry for Alzheimer's Disease Word List Memory Task (immediate and delayed memory), Digit Symbol Substitution Test, and Animal Fluency Test. Multivariable linear regression models were used to assess the associations between Framingham risk score and test-specific and global cognition Z scores. Each incremental 5% in Framingham 10-year cardiovascular disease risk was associated with lower Z scores for Digit Symbol Substitution Test (ß=-0.06 [95% CI, -0.09 to -0.03]), delayed memory (ß=-0.05 [95% CI, -0.08 to -0.01]), immediate memory (ß=-0.07 [95% CI, -0.10 to -0.03]), and global cognition (ß=-0.05 [95% CI, -0.09 to -0.02]). Socioeconomic status, particularly race or ethnicity and monthly income levels, were strong effect measure modifiers of the associations. Conclusions Lower cardiovascular risk factors are associated with better cognitive function.

Remdesivir for COVID-19 and acute kidney injury: disproportionality analysis of data from the U.S. Food and Drug Administration Adverse Event Reporting System.

BACKGROUND: Evidence about remdesivir-associated acute kidney injury (AKI) among patients with novel coronavirus disease 2019 (COVID-19) was controversial. AIM: To investigate the signal of disproportionate reporting of remdesivir-related AKI in COVID-19 patients over time with data from US Food and Drug Administration Adverse Event Reporting System. METHOD: Adverse events in COVID-19 patients reported between April 2020 and September 2022 were included. Reporting odds ratios (RORs) of AKI and renal disorders (a more sensitive definition for AKI) were estimated to compare remdesivir with other medications prescribed in comparable situations of COVID-19. RESULTS: During the entire study period, significant signals were identified for remdesivir-related AKI (ROR 2.00, 95% CI: 1.83-2.18) and renal disorder (ROR 2.35, 95% CI: 2.17-2.54) when compared to all comparable drugs. However, in the third quarter of 2022 (the most recent quarter) signals disappeared as the ROR of AKI was 1.50 (95% CI 0.91-2.45) and ROR of renal disorder was 1.69 (95% CI 1.06-2.70). Number of signals in sensitivity analyses and the proportion of AKI in remdesivir-associated events decreased over time. CONCLUSION: In COVID-19 patients, we observed diminishing signals of remdesivir-associated AKI over time and no significant signal in the most recent quarter, suggesting remdesivir might not be nephrotoxic.

Social Mediators of the Association Between Depression and Falls Among Older Adults.

OBJECTIVES: To investigate the role of social factors in the association between depression and falls among older adults. METHODS: The sample included data from 3443 older adults from three waves of the Health and Retirement Study (2010-2014). A Lifestyle Questionnaire was used to measure social engagement, social network contact, and neighborhood social context. Mediating effects of social factors were estimated through causal mediation analysis. Results: Poorer social engagement and network contact were associated with greater likelihood of falls, while poorer neighborhood context was associated with greater likelihood of fall injuries. Social engagement mediated a significant portion of the effect of depression on falls (OR: 1.03, 95% CI: 1.00, 1.06), and neighborhood context mediated a portion of the effect of depression on fall injuries (OR: 1.03, 95% CI: 1.00, 1.07). Discussion: The direct and indirect impacts of social factors suggest that considering them may help improve existing fall prevention approaches.

Dietary Patterns and Obesity in Chinese Adults: A Systematic Review and Meta-Analysis.

Certain dietary patterns are associated with an increased risk of obesity and its comorbidities. However, these associations vary across populations. The prevalence of obesity has been rising amid a drastic nutrition transition in China during the country's rapid economic growth. This systematic review and meta-analysis were conducted to summarize how dietary patterns are associated with obesity in the Chinese population. We searched for articles from 1 January 2000 to 1 February 2022 in PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Scopus that assessed the relationship between dietary patterns and obesity outcomes. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using a random effects model. From the 2556 articles identified from the search, 23 articles were included in the analysis. We found that the traditional Chinese dietary pattern was associated with a lower risk of overweight/obesity (OR = 0.69, 95% CI: 0.57, 0.84, p < 0.001), whereas the Western dietary pattern was associated with a higher OR of overweight/obesity, but not reaching statistical significance (OR = 1.34, 95% CI: 0.98, 1.84, p = 0.07). There were inconsistent results for other dietary patterns, such as meat/animal protein and plant/vegetarian patterns. In conclusion, the traditional Chinese diet characterized by vegetables, rice, and meat was associated with a lower risk of obesity. The heterogeneity in characterizing dietary patterns contributes to the inconsistency of how dietary patterns are associated with obesity in the Chinese population.

Association between the triglyceride-glucose index and carotid plaque incidence: a longitudinal study.

BACKGROUND: Carotid plaque and triglyceride-glucose (TyG) index are associated with insulin resistance. However, a highly debated question is whether there is an association between the TyG index and carotid plaque incidence. Thus we performed an in-depth longitudinal study to investigate the relationship between carotid plaque occurrence and the TyG index among Chinese individuals. METHODS: Two thousand and three hundred seventy subjects (1381 males and 989 females) were enrolled and followed up for three years. The subjects were stratified into four groups based on the quartile of the TyG index at baseline. Univariate and multivariate Cox proportional hazard models were conducted to examine the role of TyG played in the carotid plaque. The strength of association was expressed as hazard ratio (HR) and 95% confidence interval (CI). RESULTS: After three years of follow-up, 444 subjects were detected with newly formed carotid plaque. The overall 3-year cumulative carotid plaque incidence was 18.7%, and the risk of carotid plaque increased with elevated TyG index (p < 0.001). The Cox regression analysis showed that males (HR: 1.33, 95% CI: 1.10-1.61), and people with higher systolic blood pressure (HR:1.01, 95% CI: 1.01-1.02), lower high-density lipoprotein cholesterol (HR: 0.68, 95% CI: 0.50-0.93), diabetes (HR: 2.21, 95% CI: 1.64-2.97), and hypertension (HR:1.49, 95% CI: 1.23-1.81) had a significantly increased risk for the carotid plaque formation. Similar results remained in the sensitivity analysis. CONCLUSIONS: The TyG index can be used as a dose-responsive indicator of carotid plaque in the Chinese population. Elderly males with dyslipidemia, diabetes, or hypertension should be more vigilant about their TyG index since they are susceptible to developing carotid plaque. Physicians are encouraged to monitor the TyG index to help identify and treat patients with carotid plaque at an early stage.

Patterns of depressive symptoms over 16 Years with incident dementia: The Health and Retirement Study.

The associations of patterns of depressive symptoms, including trajectories of depressive symptoms and significant depressive symptoms among older adults over a long period of time with incident dementia are not frequently studied. We aimed to examine the associations of patterns of depressive symptoms among older adults with incident dementia. Participants of the Health and Retirement Study from 1994 to 2018 with information of incident dementia and complete measurements of depressive symptoms were included. Depressive symptoms assessed on 8 waves between 1994 and 2010 using the 8-item Center for Epidemiologic Studies Depression (CES-D) Scale. Significant depressive symptoms were defined as ≥4 points in the CES-D. Trajectories of depressive symptoms and significant depressive symptoms were identified. Cox proportional hazards models were used to examine the associations of patterns of depressive symptoms with incident dementia. A total of 6317 participants were included in the analysis. Over the follow-up period of 8 years, trajectories of "increase from mild" (hazards ratio (HR): 1.84, 95% confidence interval (CI): 1.29, 2.63) and "persistently high" (HR: 1.76, 95% CI: 1.17, 2.65) depressive symptoms were associated with higher risk of incident dementia, after adjustment for covariates. Future studies are needed to examine the interaction of depression in different stages of life on incident dementia. Studies are also expected to estimate the effect of preventing dementia through reducing depressive symptoms.

Closing the Gap Between Observational Research and Randomized Controlled Trials for Prevention of Alzheimer Disease and Dementia.

Although observational studies have identified modifiable risk factors for Alzheimer disease and related dementias (ADRD), randomized controlled trials (RCTs) of risk factor modification for ADRD prevention have been inconsistent or inconclusive. This finding suggests a need to improve translation between observational studies and RCTs. However, many common features of observational studies reduce their relevance to designing related RCTs. Observational studies routinely differ from RCTs with respect to eligibility criteria, study population, length of follow-up, treatment conditions, outcomes, and effect estimates. Using the motivating example of blood pressure reduction for ADRD prevention, we illustrate the need for a tighter connection between observational studies and RCTs, discuss barriers to using typically reported observational evidence in developing RCTs, and highlight methods that may be used to make observational research more relevant to clinical trial design. We conclude that the questions asked and answered by observational research can be made more relevant to clinical trial design and that better use of observational data may increase the likelihood of successful, or at least definitive, trials. Although we focus on improving translation of observational studies on risk factors for ADRD to RCTs in ADRD prevention, the overarching themes are broadly applicable to many areas of biomedical research.

Serious Cardiovascular Adverse Events Associated with Hydroxychloroquine/Chloroquine Alone or with Azithromycin in Patients with COVID-19: A Pharmacovigilance Analysis of the FDA Adverse Event Reporting System (FAERS).

BACKGROUND: The use of hydroxychloroquine or chloroquine (HCQ/CQ) as monotherapy or combined with azithromycin for the treatment of coronavirus disease 2019 (COVID-19) may increase the risk of serious cardiovascular adverse events (SCAEs). OBJECTIVE: Our objective was to describe and evaluate the risk of SCAEs with HCQ/CQ as monotherapy or combined with azithromycin compared with that for therapeutic alternatives. METHODS: We performed a disproportionality analysis and descriptive case series using the US FDA Adverse Event Reporting System. RESULTS: Compared with remdesivir, HCQ/CQ was associated with increased reporting of SCAEs (reporting odds ratio [ROR] 2.1; 95% confidence interval [CI] 1.8-2.5), torsade de pointes (TdP)/QTc prolongation (ROR 35.4; 95% CI 19.4-64.5), and ventricular arrhythmia (ROR 2.5; 95% CI 1.6-3.9); similar results were found in comparison with other therapeutic alternatives. Compared with lopinavir/ritonavir, HCQ/CQ was associated with increased reporting of ventricular arrhythmia (ROR 10.5; 95% CI 3.3-33.4); RORs were larger when HCQ/CQ was used in combination with azithromycin. In 2020, 312 of the 575 reports of SCAEs listed concomitant use of HCQ/CQ and azithromycin, including QTc prolongation (61.4%), ventricular arrhythmia (12.0%), atrial fibrillation (8.2%), TdP (4.9%), and cardiac arrest (4.4%); 88 (15.3%) cases resulted in hospitalization and 79 (13.7%) resulted in death. In total, 122 fatal QTc prolongation-related cardiovascular reports were associated with 1.4 times higher odds of reported death than those induced by SCAEs; 87 patients received more than one QTc-prolonging agent. CONCLUSIONS: Patients treated with HCQ/CQ monotherapy or HCQ/CQ + azithromycin may be at increased risk of SCAEs, TdP/QTc prolongation, and ventricular arrhythmia. Cardiovascular risks need to be considered when evaluating the benefit/harm balance of treatment with HCQ/CQ, especially with the concurrent use of QTc-prolonging agents and cytochrome P450 3A4 inhibitors when treating COVID-19.

Characteristics of movers and predictors of residential mobility in the Atherosclerosis Risk in Communities (ARIC) cohort.

Current efforts to characterize movers and identify predictors of moving have been limited. We used the ARIC cohort to characterize non-movers, short-distance movers, and long-distance movers, and employed best subset algorithms to identify important predictors of moving, including interactions between characteristics. Short- and long-distance movers were notably different from non-movers, and important predictors of moving differed based on the distance of the residential move. Importantly, systematic inclusion of interaction terms enhanced model fit and was substantively meaningful. This work has important implications for epidemiologic studies of contextual exposures and those treating residential mobility as an exposure.

Adherence to Life's Simple 7 and Cognitive Function Among Older Adults: The National Health and Nutrition Examination Survey 2011 to 2014.

Background The American Heart Association proposed the Life's Simple 7 (LS7; including diet, physical activity, smoking, body mass index, blood pressure, plasma fasting glucose, total cholesterol) to promote cardiovascular health. Adherence to LS7 has been found to be associated with better cognitive health as well, but the generalizability of previous studies is limited. We aimed to examine the associations of adherence to LS7 and cognitive function among older adults in a nationally representative sample of population. Methods and Results A total of 2585 older adults (≥60 years, 54% female, 80% non-Hispanic White) in the National Health and Nutrition Examination Survey 2011 to 2014 were included for analysis. Components of LS7 were measured, and adherence to LS7 was calculated on the basis of established cutoff points of individual components. Cognitive function was examined using the Consortium to Establish a Registry for Alzheimer's Disease Word List Memory Task (immediate and delayed memory), Digit Symbol Substitution Test (DSST), and Animal Fluency Test. Test-specific and global cognition Z scores were created. Multivariable linear regression models were conducted on the associations of adherence to LS7 with domain-specific and global cognition Z scores. Each incremental point in adherence to LS7 was associated with higher Z scores for global cognition (ß=0.05; 95% CI, 0.02-0.07), Digit Symbol Substitution Test (ß=0.05; 95% CI, 0.03-0.07), Consortium to Establish a Registry for Alzheimer's Disease Word Learning subtest immediate memory (ß=0.03; 95% CI, 0.004-0.05), and animal fluency test (ß=0.05; 95% CI, 0.02-0.07). Conclusions Greater adherence to LS7 metrics is associated with better cognitive function among older US adults in a nationally representative sample of population.