Covariate-adjusted Models Research Articles

Modified-Weight Healthy Eating Index-2015 Scores Are More Strongly Associated With Mortality Risk Than Standard Scores

BackgroundVarious diet quality scores are consistently and similarly associated with mortality risk. Emerging evidence suggests that individual diet quality components are differentially associated with mortality risk, but it is unclear whether or not modified weights reflective of relative component differences would strengthen mortality associations. ObjectiveThis study examined whether Healthy Eating Index 2015 (HEI-2015) scores with modified (vs standard) component weights are differentially associated with mortality risk. DesignThis was a longitudinal analysis of the National Health and Nutrition Examination Survey III (1988-94) with 23 years of mortality follow-up. The HEI-2015 and modified-weight scores were calculated from one 24-hour recall. The a priori Key Facets HEI was a subset score equivalently weighting fruits, vegetables, whole grains, and seafood and plant proteins. In the least absolute shrinkage and selection operator regression-weighted HEI, components were assigned weights reflecting relative mortality risk associations. Participants/settingAnalyses included 10,789 US adults (aged 20 years and older) who were not pregnant and without prior diabetes, cancer, cardiovascular disease, or chronic kidney disease diagnoses. Main outcome measuresAll-cause and cardiovascular disease mortality risk were the primary outcomes examined. Statistical analyses performedThree energy-adjusted HEI scores were assigned to quintiles; covariate-adjusted sex-stratified Cox models with age as the timescale assessed associations between and trends across quintiles of HEI scores and all-cause and cardiovascular disease mortality risk. ResultsModified-weight HEI scores were associated with 23% to 38% reduced all-cause mortality risk in the highest vs lowest quintile, whereas comparisons were only significant for women (Key Facets P = 0.02 and least absolute shrinkage and selection operator regression-weighted P = 0.001; for men P = 0.06 on both scores), trends across quintiles of modified-weight scores were significant for men and women. The HEI-2015 was not significantly associated with all-cause mortality risk, and none of the scores were associated with cardiovascular disease mortality risk. ConclusionsOnly modified-weight HEI scores were associated with reduced all-cause mortality risk. Findings suggest modified diet quality weighting schemes warrant further examination to determine their replicability.

Contemporary Use and Implications of Beta-Blockers in Patients With HFmrEF or HFpEF: The DELIVER Trial

BackgroundAlthough beta-blockers are not recommended for the treatment of heart failure with preserved ejection fraction (HFpEF) according to the latest European Society of Cardiology and American Heart Association/American College of Cardiology/Heart Failure Society of America guidelines, these therapies remain commonly used for comorbidity management. There has been concern that beta-blockers may adversely influence clinical outcomes by limiting chronotropic response in HFpEF. ObjectivesThis study sought to examine the contemporary use and implications of beta-blockers in patients with heart failure with mildly reduced ejection fraction (HFmrEF) or HFpEF. MethodsIn the DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) trial, a total of 6,263 patients with symptomatic heart failure (HF) with a left ventricular ejection fraction (LVEF) >40% were randomized to dapagliflozin or placebo across 20 countries. In this prespecified analysis, efficacy and safety outcomes were examined according to beta-blocker use at randomization. The primary outcome was cardiovascular death or worsening HF. ResultsOverall, beta-blockers were used in 5,177 patients (83%), with wide variation by geographic region. Beta-blocker use was associated with a lower risk of the primary outcome in covariate-adjusted models (HR: 0.70; 95% CI: 0.60-0.83). Dapagliflozin consistently reduced the risk of the primary outcome in patients taking beta-blockers (HR: 0.82; 95% CI: 0.72-0.94) and in patients not taking beta-blockers (HR: 0.79; 95% CI: 0.61-1.03; Pinteraction = 0.85), with similar findings for key secondary endpoints. Adverse events were balanced between patients randomized to dapagliflozin and placebo, regardless of background beta-blocker use. ConclusionsIn patients with HFmrEF or HFpEF who were enrolled in DELIVER, 4 out of 5 participants were treated with a beta-blocker. Beta-blocker use was not associated with a higher risk of worsening HF or cardiovascular death. Dapagliflozin consistently and safely reduced clinical events, irrespective of background beta-blocker use. (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure [DELIVER]; NCT03619213)

Impact of prior cancer diagnosis on pancreatic cancer outcomes: A Danish Nationwide, population-based Cohort study

BackgroundThe overall survival of pancreatic cancer (PC) remains low, underlining the need of further research to improve PC directed therapy. Some patients with PC may have experienced a prior cancer, refraining them from inclusion in clinical trials, despite not knowing the precise effect of a prior cancer on disease course of PC. ObjectiveTo examine the influence of prior cancer on the disease course in patients with PC. MethodsWe conducted a cohort study including Danish patients diagnosed with PC between 2004 and 2020 crosslinking data from the Danish Cancer Registry, the Danish National Patient Registry among several other databases. Using the Kaplan-Meier estimator, we calculated the overall and American Joint Committee on Cancer (AJCC) disease stage stratified survival, comparing patients with and without prior cancer. Furthermore, using inverse probability of treatment weighting (IPTW), we presented a covariate-adjusted model of the average treatment effect in the treated (ATT) of prior cancer on the overall PC survival and stratified for AJCC disease stage. ResultsWe included 11,147 patients diagnosed with PC, of which 906 (8.1%) had a prior cancer. Comparing patients with and without prior cancer, the IPTW-adjusted survival, indicated a slightly better survival (ATT: 1.5 months; 95% CI: 0.7; 2.2 months). After stratifying by PC tumor stage, the difference was restricted to patients with stage IV PC disease (ATT: 1.1 months; 95% CI: 0.5; 1.7 months). Patients with prior cancer were slightly less prone to present with stage IV PC disease and were more likely to not receive active treatment compared with patients without prior cancer. ConclusionPrior cancer was associated with a slightly better survival in patients with PC, but only in patients with stage IV PC disease. This is likely explained by lead time bias.

Gestational age modifies the association between exposure to fine particles and fetal death: findings from a nationwide epidemiological study in the contiguous United States

BackgroundsThe vulnerability of fetuses differs at different developmental stages, in response to environmental stressors such as fine particulate matter (PM2.5), a ubiquitous air pollutant. Whether gestational age (GA) modifies the association between prenatal fine particulate matter (PM2.5) exposure and fetal death remains unclear.MethodsWe selected approximately 47.8 million eligible United States (US) livebirth and fetal death (defined as a termination at a GA of 20–43 weeks) records from 1989 to 2004. For each record, we took the level of prenatal exposure to PM2.5 as the average concentration in the mother’s residential county during the entire gestational period, or a specific trimester (i.e., GA-specific exposure), according to well-established estimates of monthly levels across the contiguous US. First, we evaluated the associations between PM2.5 exposure and fetal death at a specific GA (i.e., GA-specific outcome) using five different logit models (unadjusted, covariate-adjusted, propensity-score, double robust, and diagnostic-score models). Double robust model was selected as the main model due to its advantages in causal inference. Then, we conducted meta-analyses to pool the estimated GA-specific associations, and explored how the pooled estimates varied with GA.ResultsAccording to the meta-analysis, all models suggested gestational PM2.5 exposure was associated with fetal death. However, there was slight heterogeneity in the estimated effects, as different models revealed a range of 3.6–10.7% increase in the odds of fetal death per 5-µg/m3 increment of PM2.5. Each 5-µg/m3 increase in PM2.5 exposure during the entire gestation period significantly increased the odds of fetal death, by 8.1% (95% confidence interval [CI]: 5.1–11.2%). In terms of GA-specific outcomes, the odds of fetal death at a GA of 20–27, 28–36, or ≥ 37 weeks increased by 11.0% (5.9–16.4%), 5.2% (0.4–10.1%), and 8.3% (2.5–14.5%), respectively. In terms of GA-specific exposure, the odds of fetal death increased by 6.0% (3.9–8.2%), 4.1% (3.9–8.2%), and 4.3% (0.5–8.2%) with 5-µg/m3 increases in PM2.5 exposure during the first, second, and third trimester, respectively. The association had the largest effect size (odds ratio = 1.098, 95% CI: 1.061–1.137) between PM2.5 exposure during early gestation (i.e., first trimester) and early fetal death (i.e., 20–27 weeks).ConclusionsPrenatal exposure to PM2.5 was significantly associated with an increased risk of fetal death. The association was varied by gestational-age-specific exposures or outcomes, suggesting gestation age as a potential modifier on the effect of PM2.5. The fetus was most vulnerable during the early stage of development to death associated with PM2.5 exposure.

Reminiscence and Digital Storytelling to Improve the Social and Emotional Well-Being of Older Adults With Alzheimer's Disease and Related Dementias: Protocol for a Mixed Methods Study Design and a Randomized Controlled Trial.

Increasing attention is being given to the growing concerns about social isolation, loneliness, and compromised emotional well-being experienced by young adults and older individuals affected by Alzheimer disease and related dementias (ADRD). Studies suggest that reminiscence strategies combined with an intergenerational approach may yield significant social and mental health benefits for participants. Experts also recommended the production of a digital life story book as part of reminiscence. Reminiscence is typically implemented by trained professionals (eg, social workers and nurses); however, there has been growing interest in using trained volunteers owing to staffing shortages and the costs associated with reminiscence programs. The proposed study will develop and test how reminiscence offered by trained young adult volunteers using a digital storytelling platform may help older adults with ADRD to improve their social and emotional well-being. The proposed project will conduct a randomized controlled trial to assess the effects of the intervention. The older and young adult participants will be randomly assigned to the intervention (reminiscence based) or control groups and then be randomly matched within each group. Data will be collected at baseline before the intervention, in the middle of the intervention, at end of the intervention, and at 3 months after the intervention. An explanatory sequential mixed methods design will be used to take advantage of the strengths of both quantitative and qualitative methods. The quantitative data from surveys will be entered into SPSS and analyzed using covariate-adjusted linear mixed models for repeated measures to compare the intervention and control groups over time on the major outcomes of participants. Conventional content analysis of qualitative interviews will be conducted using data analysis software. The project was modified to a telephone-based intervention owing to the COVID-19 pandemic. Data collection started in 2020 and ended in 2022. In total, 103 dyads were matched at the beginning of the intervention. Of the 103 dyads, 90 (87.4%) dyads completed the midtest survey and 64 (62.1%) dyads completed the whole intervention and the posttest survey. Although we are still cleaning and finalizing data analyses, the preliminary results from both quantitative and qualitative data showed promising results of this intergenerational reminiscence approach that benefits both the older adults who have cognitive impairments and the young adult participants. Intergenerational reminiscence provided by young adult college student offers promising benefits for both the younger and older generations. Future studies may consider scaling up this pilot into a trackable, replicable model that includes more participants with diverse background (eg, public vs private college students and older adults from other agencies) to test the effectiveness of this intervention for older adults with ADRD. ClinicalTrials.gov NCT05984732; https://classic.clinicaltrials.gov/ct2/show/NCT05984732. DERR1-10.2196/49752.

Association between arthritis and hand grip strength indices combined with anthropometry in an older Korean population.

Hand grip strength (HGS) is related to arthritis and all-cause mortality. Many studies have examined the association between HGS and arthritis, but these studies did not consider relative HGS indices. The objectives of this study were to examine the association between arthritis and HGS indices in an older Korean population and to compare an absolute HGS index and a relative HGS indices. In a large-scale cross-sectional study, a total of 16,860 subjects older than 50 years from the Korea National Health and Nutrition Survey from 2014 to 2019 were included for statistical analysis. A binary logistic regression model was used to examine the association between arthritis and HGS indices in crude and covariate-adjusted models. In the crude analysis, all anthropometric and HGS indices were associated with arthritis except for weight in men. In adjusted models 1 and 2, among the anthropometric indices, waist circumference (WC) and waist-to-height ratio (WHtR) were associated with arthritis in men but not in women. Absolute HGS and all relative HGS indices showed a negative association with arthritis among both men and women, and the magnitude of the association of arthritis with the absolute HGS index and the relative HGS indices was similar. However, the magnitude of the association between all HGS indices and arthritis was higher for men than for women except in the crude analysis. Absolute and relative HGS indices had negative associations with arthritis, and the magnitude of the association between the absolute HGS index and arthritis and between the relative HGS indices and arthritis was similar in all models. To our knowledge, this is the first report of an association between arthritis and relative HGS indices, which was not observed in previous studies.

Favorable Dietary Patterns Associated with Lower Incidence of Metabolic Syndrome in Middle-Aged Japanese Men: A Prospective Cohort Study.

Dietary patterns, such as selecting what food to regularly eat, may play role in reducing the incidence of metabolic syndrome (MetS). This study examined the causal relationships of Japanese dietary patterns and the relationship with the risk of MetS onset using a prospective cohort design. Data of annual health checks between 2008 and 2017 were analyzed, and middle-aged men and women (n=3,298 and 3,925, respectively) were followed up for 15,498 and 19,459 person-years, respectively. We investigated six dietary patterns using a questionnaire, and the participants were divided into low, middle, and high dietary score groups. During the follow-up period, cases of new-onset MetS were found in 698 men (21.2%) and 350 women (8.2%). Covariate-adjusted Cox proportional hazard models revealed that the risk of new-onset MetS was significantly lower in the male participants who responded that they "often eat vegetables" (HR: 0.77, 95% CI: 0.66-0.91). For dietary score, the male participants had significantly lower adjusted HRs of MetS onset in the middle-score group (HR: 0.80, 95% CI: 0.69-0.94) and high-score group (HR: 0.54, 95% CI: 0.41-0.72) compared to the low-score group. On the other hand, there was no association of each dietary pattern and dietary score with new-onset MetS among the female participants. This study found that favorable dietary patterns are associated with a lower risk of MetS; thus, education that aims to encourage a favorable diet may have an important role in reducing the incidence of MetS in middle-aged men.

Are there Interindividual Responses of Cardiovascular Disease Risk Markers to Acute Exercise? A Replicated Crossover Study.

Using a replicated crossover design, we quantified the response heterogeneity of postprandial cardiovascular disease (CVD) risk marker responses to acute exercise. Twenty men (mean (SD) age, 26 (6) years; BMI, 23.9 (2.4) kg·m-2) completed four, 2-day conditions (two control, two exercise) in randomised orders. On days 1 and 2, participants rested and consumed two high-fat meals over 9-h. Participants ran for 60-mins (61 (7)% of peak oxygen uptake) on day 1 (6.5-7.5 h) of both exercise conditions. Time-averaged total-area-under-the-curve (TAUC) for triacylglycerol (TAG), glucose and insulin were calculated from 11 venous blood samples on day 2. Arterial stiffness and blood pressure responses were calculated from measurements at baseline on day 1 and at 2.5-h on day 2. Consistency of individual differences was explored by correlating the two replicates of control-adjusted exercise responses for each outcome. Within-participant covariate-adjusted linear mixed models quantified participant-by-condition interactions and individual-response SDs. Acute exercise reduced mean TAUC-TAG (-0.27 mmol·L-1 h; Cohen's d = 0.29, P = 0.017) and TAUC-insulin (-24.45 pmol·L-1 h; Cohen's d = 0.35, P = 0.022) vs. control, but led to negligible changes in TAUC-glucose and the vascular outcomes (Cohen's d ≤ 0.41, P ≥ 0.106). Small-to-moderate, but nonsignificant, correlations were observed between the two response replicates (r = -0.40 to 0.15, P ≥ 0.066). We did not detect any individual response heterogeneity. All participant-by-condition interactions were P ≥ 0.137, and all individual-response SDs were small with wide 95% confidence intervals overlapping zero. Large trial-to-trial within-subject variability inhibited detection of consistent inter-individual variability in postprandial metabolic and vascular responses to acute exercise.

Associations between maternal gestational diabetes metformin or insulin treatment and offspring growth trajectories from birth to 60 months of age: Findings from the Born in Bradford (BiB) study.

To investigate the associations between gestational diabetes mellitus (GDM) metformin or insulin treatment and offspring growth trajectories from 0 to 60 months. Participants were from the Born in Bradford birth cohort study. Using covariate-adjusted multilevel linear spline models (4 splines: 0-1.6, 1.6-6, 6-17 and 17-60 months), we compared weight, height and body mass index (BMI) z-score trajectories of: (1) 76 offspring exposed to metformin (OGDM-Metformin) and 420 offspring exposed to insulin (OGDM-Insulin); (2) OGDM-Metformin and 9171 offspring not exposed to GDM (No-GDM); (3) OGDM-Insulin and No-GDM. (1) OGDM-Metformin had comparable growth trajectories to OGDM-Insulin from 0 to 60 months. (2) OGDM-Metformin had a lower mean birthweight z-score than No-GDM. OGDM-Metformin had faster changes in height z-score (0.13 [95% CI 0.026, 0.24]) from 17 to 60 months and by 60 months, had comparable mean BMI z-score to No-GDM. (3) OGDM-insulin had lower mean birthweight and height z-scores than No-GDM. OGDM-Insulin had faster changes in weight (0.32 [0.021, 0.62]) and height (0.50 [0.087, 0.91]) from 1.6 to 6 months and by 60 months, had comparable mean BMI z-score to No-GDM. GDM metformin treatment was not associated with differences in offspring growth trajectories compared to insulin treatment. Both metformin and insulin-exposed offspring had comparable BMI z-score to No-GDM by 60 months.

Association of retinopathy with risk of all-cause and specific-cause mortality in the National Health and Nutrition Examination Survey, 2005 to 2008.

This study aimed to elucidate the relationship between retinopathy status or severity and the all-cause and specific-cause mortality risk based on the updated National Health and Nutrition Examination Survey (NHANES) database and 2019 Public Access Link mortality file. In this prospective cohort study, a total of 6,797 participants aged over 40 years based on NHANES 2005-2008 were analyzed. The severity of retinopathy was classified into 4 grades-no retinopathy, mild non-proliferative retinopathy (NPR), moderate to severe NPR, and proliferative retinopathy (PR). Multiple covariate-adjusted Cox proportional hazards regression models and Fine and Gray competing risk regression models were used to assess the all-cause and cause-specific mortality risks, respectively. The propensity score matching (PSM) approach was also applied additionally to adequately balance between-group covariates to validate our findings. A final total of 4,808 participants representing 18,282,772 United States (US) non-hospitalized participants were included for analysis, 50.27% were male (n = 2,417), 55.32% were non-hispanic white (n = 2,660), and mean [SE] age, 56.10 [0.40] years. After a median follow-up of 12.24 years (interquartile range, 11.16-13.49 years), 1,164 participants died of all-cause mortality, of which 941 (80.84%) died without retinopathy and 223 (19.16%) died with retinopathy at baseline. The presence of retinopathy was associated with increased all-cause mortality, cardiovascular disease (CVD), and diabetes mellitus (DM)-specific mortality, and the results remain consistent after PSM. Severity analysis showed that only mild NPR was associated with an increased all-cause mortality risk (hazard ratio (HR) = 2.01; 95% confidence interval (CI), 1.00-4.03), while increased CVD and DM-specific mortality risk were associated with all grades of retinopathy and were exponentially greater with increasing retinopathy severity, and the trend test was also significant (P for trend 0.004 and 0.04, respectively). Our findings suggest that the diagnosis of retinopathy is an independent risk factor for all-cause mortality in people over 40 years old. Retinopathy grading is significantly associated with the survival risk of patients with CVD or DM, it can be a valuable predictor in the stratified management and risk warning of CVD or DM patients, as well as in the monitoring of systemic vasculopathy status.

Urban Form Metrics for Promoting Walking: Street Layouts and Destinations.

There is evidence that higher street connectivity and availability of destinations can support walking behavior. However, the availability of data and comparability between previous studies remain a challenge. Based on a large Canadian adult sample, this study examined the associations between street layout and walking behaviors and explored whether objectively measured destinations may mediate these relationships. This study used data from 12,378 adults from Alberta's Tomorrow Project (ATP), a prospective cohort study conducted in Alberta, Canada. Walking behaviors were obtained by questionnaires. Street layout and destination measures were calculated objectively. Covariate-adjusted multivariate linear models estimated the associations between the space syntax street integration and duration of transport and leisure walking. The mediation effects of the availability of destinations in these associations were tested by the structural equation modelling. Street integration was significantly positively associated with transportation walking (b=0.01, 95% CI 0.00, 0.01, p = 0.01) (indirect effect). The availability of destinations partially mediated this association. Using the natural movement theory in space syntax, our study provides insights into using street layouts as a primary measure to (re)design the built environment to support walking.

Low handgrip strength with or without asymmetry is associated with elevated all-cause mortality risk in older Chinese males.

This study aimed to examine the link between handgrip strength (HGS) asymmetry and mortality risk among older Chinese adults. These analyses were conducted using data from adults aged 60 years and older from the 2011-2013 waves of the China Health and Retirement Longitudinal Study, using baseline participant data collected in 2011. Proxy-reported information was used to assess the mortality outcomes of the participants over a 2-year follow-up. The highest recorded HGS values for each hand were used to compute the HGS asymmetry ratio (non-dominant HGS/dominant HGS) and HGS weakness (Male<26 kg, Female<16 kg). Covariate-adjusted Cox models were employed to gauge the relationship between abnormal HGS and mortality risk. Overall, 5083 adults were enrolled in this study, of whom 50.15% (2549/5083) were male. The proportions of low HGS alone, HGS asymmetry alone, and asymmetric and low HGS were 6.43%, 30.95%, and 9.22%, respectively, in males, and 4.81%, 35.87%, and 9.55%, respectively, in females. A total of 96 and 78 deaths were recorded for male (3.77%) and female (3.08%) participants, respectively, over the 2-year follow-up period. Significant differences in mortality were observed between the different HGS groups for both sexes. An adjusted Cox regression analysis model confirmed that only low HGS (P = 0.047, hazard ratio [HR] = 1.949, 95% confidence interval [95% CI]: 1.008-3.768) and low HGS with asymmetry (P = 0.007, HR = 2.152, 95% CI: 1.231-3.764) were significantly associated with mortality risk in older males. The results revealed that low HGS with or without asymmetry was associated with a higher risk of death over a 2-year follow-up interval in older Chinese males. Geriatr Gerontol Int 2023; 23: 692-699.

Aging-Related Comorbidity Burden Among Women and Men With or At-Risk for HIV in the US, 2008-2019

Despite aging-related comorbidities representing a growing threat to quality-of-life and mortality among persons with HIV (PWH), clinical guidance for comorbidity screening and prevention is lacking. Understanding comorbidity distribution and severity by sex and gender is essential to informing guidelines for promoting healthy aging in adults with HIV. To assess the association of human immunodeficiency virus on the burden of aging-related comorbidities among US adults in the modern treatment era. This cross-sectional analysis included data from US multisite observational cohort studies of women (Women's Interagency HIV Study) and men (Multicenter AIDS Cohort Study) with HIV and sociodemographically comparable HIV-seronegative individuals. Participants were prospectively followed from 2008 for men and 2009 for women (when more than 80% of participants with HIV reported antiretroviral therapy use) through last observation up until March 2019, at which point outcomes were assessed. Data were analyzed from July 2020 to April 2021. HIV, age, sex. Comorbidity burden (the number of total comorbidities out of 10 assessed) per participant; secondary outcomes included individual comorbidity prevalence. Linear regression assessed the association of HIV status, age, and sex with comorbidity burden. A total of 5929 individuals were included (median [IQR] age, 54 [46-61] years; 3238 women [55%]; 2787 Black [47%], 1153 Hispanic or other [19%], 1989 White [34%]). Overall, unadjusted mean comorbidity burden was higher among women vs men (3.4 [2.1] vs 3.2 [1.8]; P = .02). Comorbidity prevalence differed by sex for hypertension (2188 of 3238 women [68%] vs 2026 of 2691 men [75%]), psychiatric illness (1771 women [55%] vs 1565 men [58%]), dyslipidemia (1312 women [41%] vs 1728 men [64%]), liver (1093 women [34%] vs 1032 men [38%]), bone disease (1364 women [42%] vs 512 men [19%]), lung disease (1245 women [38%] vs 259 men [10%]), diabetes (763 women [24%] vs 470 men [17%]), cardiovascular (493 women [15%] vs 407 men [15%]), kidney (444 women [14%] vs 404 men [15%]) disease, and cancer (219 women [7%] vs 321 men [12%]). In an unadjusted model, the estimated mean difference in comorbidity burden among women vs men was significantly greater in every age strata among PWH: age under 40 years, 0.33 (95% CI, 0.03-0.63); ages 40 to 49 years, 0.37 (95% CI, 0.12-0.61); ages 50 to 59 years, 0.38 (95% CI, 0.20-0.56); ages 60 to 69 years, 0.66 (95% CI, 0.42-0.90); ages 70 years and older, 0.62 (95% CI, 0.07-1.17). However, the difference between sexes varied by age strata among persons without HIV: age under 40 years, 0.52 (95% CI, 0.13 to 0.92); ages 40 to 49 years, -0.07 (95% CI, -0.45 to 0.31); ages 50 to 59 years, 0.88 (95% CI, 0.62 to 1.14); ages 60 to 69 years, 1.39 (95% CI, 1.06 to 1.72); ages 70 years and older, 0.33 (95% CI, -0.53 to 1.19) (P for interaction = .001). In the covariate-adjusted model, findings were slightly attenuated but retained statistical significance. In this cross-sectional study, the overall burden of aging-related comorbidities was higher in women vs men, particularly among PWH, and the distribution of comorbidity prevalence differed by sex. Comorbidity screening and prevention strategies tailored by HIV serostatus and sex or gender may be needed.

Longitudinal Assessment of Association Between Tobacco Use and Tobacco Dependence Among Adults: Latent Class Analysis of the Population Assessment of Tobacco and Health Study Waves 1-4.

With increasing tobacco product varieties, understanding tobacco use (TU) profiles and their associations with tobacco dependence (TD) has also become increasingly challenging. We aimed to identify TU profiles and their associations with TD over time, and to identify subgroups with high risk of TD. We included 3463 adult recent tobacco users who had complete TU and TD data across waves 1-4 of the Population Assessment of Tobacco and Health (PATH) study. We used a composite index of TD and a summed TD score from an established 16-item TD measure. We applied a latent class analysis to identify TU profiles based on participants' usage of eight common tobacco product groups at each survey wave and to check the stability of the TU profiles over time. We then used generalized estimating equations regressions to evaluate the longitudinal TU-TD association, adjusting for potential confounders. We identified three distinct TU profiles that remained consistent across four survey waves: Dominant cigarette users (62%-68%), poly users with high propensity of using traditional cigarettes, e-cigarettes, and cigars (24%-31%), and dominant smokeless product users (7%-9%). Covariate-adjusted models showed that TD was significantly lower among the poly users and the dominant smokeless users, compared to that among the dominant cigarette users. Both TU profiles and their associations with TD were stable over time at the population level. Poly users and smokeless product users were consistently associated with lower TD than cigarette-dominant users, suggesting the need for tailored tobacco cessation interventions for users with different TU profiles. The finding of consistent TU profiles across four survey waves extends the current literature in capturing TU patterns in an evolving tobacco product landscape. The finding of the overall higher level of TD among the cigarette-dominant users compared to the other TU latent profiles (the Cig+eCig+Cigar dominant poly users and the dominant smokeless product users) can help identify high-risk groups for potential interventions. Our application of innovative statistical methods to high-quality longitudinal data from the PATH study helps improve the understanding of the dynamic TU-TD relationship over time.

Accurate protamine:heparin matching (not just smaller protamine doses) decreases postoperative bleeding in cardiac surgery; results from a high-volume academic medical center.

A multidisciplinary Quality Assurance/Performance Improvement study to identify the incidence of "heparin rebound" in our adult cardiac surgical population instead detected a thromboelastometry pattern suggestive of initial protamine overdose in 34% despite Hepcon-guided anticoagulation management. Analysis of our practice led to an intervention that made an additional lower-range Hepcon cartridge available to the perfusionists. One year later, an IRB-approved retrospective study was conducted in >500 patients to analyze the effects of the intervention, specifically focusing on the impact of the initial protamine dose accuracy and 18-h mediastinal chest tube drainage (MCTd). No differences were observed between group demographics, surgical procedures, duration of CPB or perioperative blood product transfusion. Both groups were managed using the same perfusion and anesthesia equipment, strategies, and protocols. The median initial protamine dose decreased by 19% (p < .001) in the intervention group (170 [IQR 140-220] mg; n = 295) versus the control group (210 [180-250] mg; n = 257). Mean 18-h MCTd decreased by 13% (p < .001) in the intervention group (405.15 ± 231.54mL; n = 295) versus the control group (466.13 ± 286.73mL; n = 257). Covariate-adjusted mixed effects model showed a significant reduction of MCTd in the intervention group, starting from hour 11 after surgery (group by time interaction p = .002). Though previous investigators have associated lower protamine doses with less MCTd, this study demonstrates that more accurately matching the initial protamine dose to the remaining circulating heparin concentration reduces postoperative bleeding.

Impact of Racist Microaggressions and LGBTQ-Related Minority Stressors: Effects on Psychological Distress Among LGBTQ+ Young People of Color.

College students situated at the nexus of racial and sexual and gender minority (SGM) identities may experience multiple identity-related oppressions. We assessed whether racist microaggressions and lesbian, gay, bisexual, transgender, queer, or questioning (LGBTQ)-related minority stressors (ie, family rejection, identity concealment, racialized heterosexism and/or cisgenderism, internalized LGBTQ-phobia, and victimization) are associated with greater psychological distress among SGM college students of color (SOC) (students who identified as Hispanic/Latinx and/or any nonwhite race). Participants were a subset of SOC (n = 200) from a larger nonprobability cross-sectional study of SGM college students. Participants were recruited by using online social media platforms and university email listserves from May through August 2020. Participants completed an online Qualtrics survey using previously validated measures of minority stress, racist microaggressions, and psychological distress. Simple and covariate-adjusted multiple linear regression models were used to examine the associations between racist microaggressions and LGBTQ-related minority stressors with psychological distress. In simple linear regression models, racist microaggressions and all LGBTQ-related stressors (ie, family rejection, identity concealment, racialized heterosexism and/or cisgenderism, internalized LGBTQ-phobia, and victimization) were significantly and positively associated with greater psychological distress. In covariate-adjusted multiple linear regression, racist microaggressions, internalized LGBTQ-phobia, and LGBTQ-related family rejection (but not identity concealment, racialized heterosexism and/or cisgenderism, and victimization) were independently and significantly associated with greater psychological distress. Study findings reveal that racist microaggressions, along with LGBTQ-related family rejection and internalized LGBTQ-phobia, have a significant impact on psychological distress among SGM SOC. Public health leaders have an important opportunity for policy and program development and reform to address the identity-related mental health needs of SGM SOC.

Predictive value of the Framingham steatosis index for cardiovascular risk: a nationwide population-based cohort study.

Non-alcoholic fatty liver disease (NAFLD) is common and is associated with cardiovascular (CV) disease and mortality. The Framingham steatosis index (FSI) was recently proposed as a diagnostic marker of NAFLD and was calculated from age, body mass index, triglyceride, aspartate aminotransferase, alanine aminotransferase, diabetes history, and hypertension status. We aimed to evaluate the predictive ability of FSI for CV risk using a large-scale population dataset from the Korean National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS). Among 514,866 individuals in the NHIS-HEALS, we excluded those who died, had a history of admission due to a CV event, and were heavy drinkers. The final study cohort comprised 283,427 participants. We employed both unadjusted and covariate-adjusted models in Cox proportional hazards regression analyses to determine the association between FSI and major adverse cardiovascular events (MACEs), CV events, and CV mortality. During a median follow-up of 5.9 years, we documented 9,674, 8,798, and 1,602 cases of MACEs, CV events, and CV mortality, respectively. The incidence of MACEs was 1.28%, 2.99%, 3.94%, and 4.82% in the first to fourth quartiles of FSI, respectively. The adjusted hazard ratios (95% confidence interval) for MACEs gradually and significantly increased with the FSI quartiles [1.302 (1.215-1.395) in Q2, 1.487 (1.390-1.590) in Q3, and 1.792 (1.680-1.911) in Q4], following an adjustment for conventional CV risk factors, including age, sex, smoking, drinking, physical activities, low-density lipoprotein cholesterol, estimated glomerular filtration rate, and waist circumference. Participants in the higher quartiles of FSI exhibited a noteworthy increase in the occurrence of CV event. However, upon adjusting for relevant risk factors, the association between FSI and CV mortality did not reach statistical significance. Our study suggests that the FSI, which is a surrogate marker of NAFLD, has a prognostic value for detecting individuals at higher risk of CV events.

Reaction time in psychomotor vigilance task is related to hypoxic load in males with sleep apnea.

Oxygen saturation (SpO2 )-based parameters are more strongly linked to impaired daytime vigilance than the conventional diagnostic metrics in patients with obstructive sleep apnea (OSA). However, whether the association between SpO2 -based parameters and impaired daytime vigilance is modulated by sex, remains unknown. Hence, we investigated the interplay between sex and detailed SpO2 -based metrics and their association with impaired vigilance in patients with OSA. The study population consisted of 855 (473 males, 382 females) patients with suspected OSA who underwent overnight polysomnography and psychomotor vigilance task (PVT). The population was grouped by sex and divided into quartiles (Q1-Q4) based on median reaction times (RTs) in the PVT. In addition to conventional diagnostic metrics, desaturation severity (DesSev), fall severity (FallSev), and recovery severity (RecovSev) were compared between the sexes and between the best (Q1) and worst (Q4) performing quartiles by using cumulative distribution functions (CDFs). Additionally, sex-specific covariate-adjusted linear regression models were used to investigate the connection between the parameters and RTs. The CDFs showed significantly higher hypoxic load in Q4 in males compared to females. In addition, the DesSev (β = 8.05, p < 0.01), FallSev (β = 6.48, p = 0.02), RecovSev (β = 9.13, p < 0.01), and Oxygen Desaturation Index (β = 12.29, p < 0.01) were associated with increased RTs only in males. Conversely, the Arousal Index (β = 10.75-11.04, p < 0.01) was associated with impaired vigilance in females. The severity of intermittent hypoxaemia was strongly associated with longer RTs in males whereas the Arousal Index had the strongest association in females. Thus, the impact of hypoxic load on impaired vigilance seems to be stronger in males than females.

The role of prenatal violence exposure in the development of disparities in children's adiposity from birth to middle childhood.

This study examined whether women's exposure to multiple types of violence during childhood and pregnancy was associated with children's BMI trajectories and whether parenting quality moderated those associations. A cohort of 1288 women who gave birth between 2006 and 2011 self-reported their exposure to childhood traumatic events, intimate partner violence (IPV), and residential address (linked to geocoded index of violent crime) during pregnancy. Children's length/height and weight at birth and at age 1, 2, 3, 4 to 6, and 8 years were converted to BMI z scores. Observed mother-child interactions were behaviorally coded during a dyadic teaching task. Covariate-adjusted growth mixture models identified three trajectories of children's BMI from birth to 8 years old: Low-Stable (17%), Moderate-Stable (59%), and High-Rising (22%). Children whose mothers experienced more types of IPV during pregnancy were more likely to be in the High-Rising than the Low-Stable (odds ratio [OR] = 2.62; 95% CI: 1.27-5.41) trajectory. Children whose mothers lived in higher crime neighborhoods were more likely to be in the High-Rising than the Low-Stable (OR = 1.11; 95% CI:1.03-1.17) or Moderate-Stable trajectories (OR = 1.08; CI: 1.03-1.13). Main effects of childhood traumatic events and moderation by parenting were not detected. Maternal experiences of violence during pregnancy increase children's risk for developing overweight, highlighting intergenerational transmission of social adversity in children's health.

Covariate-specific ROC curve analysis can accommodate differences between covariate subgroups in the evaluation of diagnostic accuracy

ObjectivesWe present an illustrative application of methods that account for covariates in receiver operating characteristic (ROC) curve analysis, using individual patient data on D-dimer testing for excluding pulmonary embolism. Study Design and SettingBayesian nonparametric covariate-specific ROC curves were constructed to examine the performance/positivity thresholds in covariate subgroups. Standard ROC curves were constructed. Three scenarios were outlined based on comparison between subgroups and standard ROC curve conclusion: (1) identical distribution/identical performance, (2) different distribution/identical performance, and (3) different distribution/different performance. Scenarios were illustrated using clinical covariates. Covariate-adjusted ROC curves were also constructed. ResultsAge groups had prominent differences in D-dimer concentration, paired with differences in performance (Scenario 3). Different positivity thresholds were required to achieve the same level of sensitivity. D-dimer had identical performance, but different distributions for YEARS algorithm items (Scenario 2), and similar distributions for sex (Scenario 1). For the later covariates, comparable positivity thresholds achieved the same sensitivity. All covariate-adjusted models had AUCs comparable to the standard approach. ConclusionSubgroup differences in performance and distribution of results can indicate that the conventional ROC curve is not a fair representation of test performance. Estimating conditional ROC curves can improve the ability to select thresholds with greater applicability.