Covariate-adjusted Models Research Articles

Abstract 4123872: Unsupervised clustering analysis of large-scale proteomics data identifies molecular phenogroups of heart failure in a population-based cohort

Background: Heart failure (HF) is a heterogeneous syndrome with high mortality. Previous work characterizing HF subgroups primarily relied on clinical data to cluster patients, an approach constrained by the boundaries of documented clinical features. Clustering based on biomarker data, such as proteomics, may provide insights into underlying molecular processes. However, few studies have used this approach, and all used targeted cardiovascular proteomics panels and a restricted HF ejection fraction group. Hypothesis: We used unsupervised clustering analysis to characterize molecular phenogroups in a population-based HF cohort using a large-scale array of circulating plasma proteins. We hypothesized that distinct proteomic-defined phenogroups would exhibit differences in clinical characteristics, mortality, and protein expression. Methods: We measured 7151 SOMAmers (Slow off-rate modified aptamers) targeting human proteins via the SomaLogic 7K SomaScan assay in 1351 HF patients. After feature selection, 831 SOMAmers were used in k-means clustering of patients via R package “ConsensusClusterPlus.” Phenogroups were compared for clinical characteristics, all-cause mortality, and protein expression. Results: Three phenogroups were identified, exhibiting different clinical characteristics ( Table 1 ) and survival probabilities (5-year survival probability in phenogroup 1: 65% [61%, 68%], phenogroup 2: 45% [40%, 51%], and phenogroup 3: 26% [22%, 30%]). In covariate-adjusted Cox models, membership in phenogroups 2 and 3 was significantly associated with increased rate of mortality compared to phenogroup 1. Phenogroups did not differ by ejection fraction or New York Heart Association class. Pathway overrepresentation analysis of differentially expressed SOMAmers identified pathways associated with inflammatory response and immune cell trafficking. Conclusions: Unsupervised clustering analysis using large-scale proteomics data identified three HF phenogroups with different proteomic signatures, clinical characteristics, and outcomes. Future work is necessary to elucidate how molecular differences contribute to heterogeneity in HF to improve risk stratification beyond current recommended clinical guidelines.

Abstract 4125939: Bayesian re-analysis of the STeroids to REduce Systemic inflammation after infant heart Surgery (STRESS) trial

Background: Prophylactic steroids are often used to reduce the systemic inflammatory response to cardiopulmonary bypass in infants undergoing heart surgery. The STRESS trial found that the likelihood of a worse outcome did not differ between infants randomized to methylprednisolone vs placebo in a risk-adjusted primary analysis (adjusted odds ratio [OR], 0.86; 95% CI, 0.71 to 1.05; P=0.14). However, secondary unadjusted analyses showed possible benefits with methylprednisolone. We re-analyzed the STRESS trial using Bayesian analytics to assess probability of benefit with methylprednisolone. Methods: We used a covariate-adjusted proportional odds model using the original STRESS trial model covariates and primary outcome (a ranked composite of death, transplant, major complications and post-op length of stay). We assessed effect thresholds from OR 0.6 to 1.25 (OR <1 conveys benefit, OR >1 conveys harm). We assumed a neutral probability of benefit vs harm with weak prior belief (SD of the normal prior distribution = 0.425). In sensitivity analyses, we evaluated pessimistic (5%-30% prior likelihood of benefit), neutral and optimistic (70%-95% prior likelihood of benefit) prior beliefs, and controlled strength of prior belief as weak (SD = 0.425), moderate (SD = 0.215) and strong (SD = 0.135). We compared posterior distribution of the OR under these priors with the reference results under the vague prior distribution. Analyses consisted of 10 Markov Chain Monte Carlo simulations each consisting of 2000 iterations with a 1000 iteration burn-in to ensure proper posterior convergence. Results: In primary analysis, the posterior probability of benefit from methylprednisolone was 92% and the probability of harm was 8%. The mean absolute benefit was 12%. In sensitivity analyses, the probability of benefit was ≥ 79% for all informative priors except the most pessimistic (Table/Figure). Conclusion: In Bayesian re-analysis of the STRESS trial, probability of benefit with prophylactic methylprednisolone is high and harm is unlikely. Assessing probability of benefit or harm may be more informative than frequentist analytics relying on a p-value threshold. Another advantage is the ability to consider a range of prior evidence.

Association between secondhand smoke and liver injury among US non-smoking adults: Mediation analysis of body mass index in the NHANES.

Liver injury is a primary factor in the pathogenesis of most liver diseases, which can lead to liver failure. Secondhand smoke (SHS) is a serious public problem. This research explored the correlation between SHS and the indicators of liver injury. This cross-sectional study was based on the National Health and Nutrition Examination Survey (NHANES) 2011-2016. The relationship between SHS and indicators of liver injury was explored by the weighted linear regression model and smooth curve fitting. The weighted threshold saturation effect model tested the relationship and inflection point between them. Mediation analyses were used to explore whether body mass index (BMI) mediates the correlation between SHS and liver injury indicators. Our cross-sectional study included 3811 non-smoking participants (aged 20-80 years). The full covariate adjustment model (β= -0.05; 95% CI: -0.08 - -0.02) showed a significant and negative correlation between log cotinine and albumin (ALB). Compared to the unexposed group, the ALB, and total protein (TP) were decreased by 0.16 g/dL, 0.26 g/dL in the heavy exposure group [ALB: -0.16 (-0.26 - -0.05), TP: -0.26 (-0.38 - -0.13)], respectively. Smoothed curve fitting revealed a nonlinear relationship between log cotinine and fibrosis-4 index (FIB-4 score), with the inflection point of log cotinine at -1.72. When log cotinine was < -1.72, the log cotinine significantly and positively correlated with the FIB-4 score (β=0.27; 95% CI: 0.06-0.49). BMI partially mediated the effect of SHS exposure on ALB or TP. SHS has harmful effects on the liver in never-smoking adults. BMI partially mediated the effect of SHS exposure on ALB or TP. More prospective and basic research in the future is necessary to focus on validating our results.

Correlations between nutritional indicators and cognitive function in patients with stable schizophrenia in a hospital setting.

Cognitive impairment is a core feature of schizophrenia, and it is now clear that there is a link between nutritional indicators and cognitive functioning. This study aimed to investigate correlations between three nutritional indicators (prognostic nutritional index [PNI], geriatric nutritional risk index [GNRI], and controlling nutritional status score [CONUT]) and cognitive function in hospitalized patients with stable schizophrenia. A total of 235 patients who were hospitalized with stable schizophrenia were included. Patient demographic information was collected through self-reports or electronic medical records, and cognitive function was assessed using the Montreal Cognitive Assessment in China (MoCA-C). Information on serum albumin and total cholesterol levels, lymphocyte counts, and body mass index during the stable stage of schizophrenia was collected to calculate the PNI, GNRI, and CONUT scores, according to their respective calculation criteria. Covariate-adjusted linear regression model and ordered logistic regression model were constructed to determine the relationship between nutritional indicators and cognitive function. Overall, 90.2% of the patients were under the age of 60 years, and males comprised 60% of all patients. The median scores for MoCA-C, PNI, GNRI, and CONUT in hospitalized patients with stable schizophrenia were 18 (12,23), 52.85 (50.25,55.90), 110.85 (105.80,116.21), and 3 (3,3), respectively. The results of the correlation analysis showed that only PNI was associated with MoCA-C scores (r = 0.15, P = 0.021). This relationship was further confirmed by covariate-adjusted linear regression modeling (β = 0.147, 95%CI:0.049-0.351, p = 0.01) and ordered logistic regression modeling (OR = 0.054, 95%CI:0.001-0.106, p = 0.046). The findings revealed a significant correlation between PNI scores and MoCA-C scores in hospitalized patients with stable schizophrenia.

Real-world effectiveness of nirmatrelvir-ritonavir and molnupiravir in non-hospitalised adults with Covid-19: a population-based, retrospective cohort study cohort study

ObjectivesThe real-world effectiveness of the oral antivirals nirmatrelvir-ritonavir and molnupiravir against the SARS-CoV-2 Omicron variant remains uncertain. We aimed to estimate their effectiveness in non-hospitalised adults with Covid-19. MethodsThis retrospective cohort study used data from the Municipal Department for Public Health Services of Vienna, Austria, to identify non-hospitalised adults with confirmed SARS-CoV-2 infection between Jan-2022–May-2023. Nirmatrelvir-ritonavir users were compared with untreated controls and molnupiravir users with untreated controls by calculating adjusted risk differences (aRDs) using a covariate-adjusted logistic regression model with inverse probability weighting. Outcomes were hospitalisation and all-cause death within 28 days. ResultsWe identified 113,399 eligible cases (90,481 untreated controls, 12,166 nirmatrelvir-ritonavir users, and 10,752 molnupiravir users). Over 96% of the patients were immunised by previous infection or vaccination. In the nirmatrelvir-ritonavir analysis, the estimated risk of hospitalisation was 0.57% (95%CI, 0.35–0.78) in nirmatrelvir-ritonavir users and 1.09% (95%CI, 0.86–1.32) in untreated controls (aRD -0.53%; 95%CI, -0.77–-0.28). The estimated risk of death was 0.0% (95%CI, 0.0–0.0) in nirmatrelvir-ritonavir users and 0.13% (95%CI, 0.08–0.18) in untreated controls (aRD -0.13%, 95%CI, -0.18–-0.08). The number needed to treat to prevent hospitalisation and death was 190 (95%CI, 130–356) and 792 (95%CI, 571–1289), respectively. These statistically significant aRDs were restricted to the subgroup of patients ≥60 years. In the molnupiravir analysis, the estimated risk of hospitalisation was 1.36% (95%CI, 0.95–1.77) in molnupiravir users and 1.16% (95%CI, 0.93–1.39) in untreated controls (aRD 0.2%; 95%CI, -0.08–0.49). The estimated risk of death was 0.12% (95%CI, 0.01–0.23) in molnupiravir users and 0.14% (95%CI, 0.06–0.21) in untreated controls (aRD, -0.01%; 95%CI, -0.08–-0.06). ConclusionsAmong outpatients aged ≥60 years with Covid-19 in an Omicron-dominated era, treatment with nirmatrelvir-ritonavir was associated with a lower risk of hospitalisation and all-cause death within 28 days, albeit with wide confidence intervals and high numbers needed to treat. This finding was not observed in molnupiravir users and younger nirmatrelvir-ritonavir users.

Multidimensional Healthcare Access Barriers to Prostate-Specific Antigen Testing: A Nation-Wide Panel Study in the United States From 2006 to 2020.

Rising metastatic prostate cancer incidence has renewed debate regarding benefits of prostate-specific antigen (PSA) screening. Identifying barriers to accessing screening for individuals at high risk of lethal prostate cancer may slow this rise. We examined associations of access barriers with receipt of PSA testing, stratified by sociodemographic factors. We pooled data from male respondents to Behavior Risk Factor Surveillance Systems (BRFSS) surveys from 2006 to 2020. Questions related to affordability (insurance, cost of visits) and accommodation (regular primary care provider (PCP), physician recommending a PSA test) were considered as individual-level barriers. For availability, we linked provider density from the 2012 Area Health Resource File and estimated driving times to closest health facility within Micropolitan and Metropolitan Statistical Area (MMSA) using Google Earth Engine. These measures were used to compute a spatial accessibility index. We fit survey-weighted, covariate-adjusted logistic regression models to estimate associations of barriers with receipt of PSA within the past 2 years and examined effect modification by sociodemographic factors. There were 185,643 participants, of whom 73% were White, 11% were Black, 4% were Asian, and 11% were Hispanic. Physician recommendation was the strongest predictor of having a PSA test (aOR: 14.5, 95% CI: 13.6, 15.6). Not having a regular PCP (aOR: 0.29, 95% CI: 0.27, 0.31), insurance (aOR: 0.64, 95% CI: 0.58, 0.71), and prohibitive cost of care (aOR: 0.82, 95% CI: 0.75, 0.90) were associated with lower PSA testing. Access barriers were stronger predictors of PSA testing for Asian and White participants compared to other groups (Phet < 0.004 for insurance and regular PCP) and for those with college education compared to those without (Phet < 0.05 for insurance, perceived unaffordability). Physician recommendation was the strongest predictor of receipt of PSA testing, regardless of sociodemographic grouping. Future studies should consider access barriers jointly and across sociodemographic strata.

Sex related cardiovascular risk is non-dichotomous: artificial intelligence enhanced electrocardiography reveals continuum of risk in females

Abstract Background Females are typically underserved in cardiovascular medicine and often considered lower risk of cardiovascular disease. The use of sex as a dichotomous variable for risk stratification fails to capture the heterogeneity of risk within each sex. Purpose We aimed to develop an artificial intelligence-enhanced ECG (AI-ECG)-derived continuous sex score that can capture the continuum of risk and sex phenotypes within each sex, with the particular goal of addressing the female disadvantage. Methods We trained a convolution neural network to identify sex using the 12-lead ECG. The derivation cohort was 1,163,401 ECGs from 189,538 subjects from a USA secondary care hospital cohort and validated inthe UK Biobank (UKB). The model outputs a continuous value from 0 to 1 for sex prediction. The AI-ECG sex discordance score is the difference between predicted sex and biological sex. Results AI-ECG accurately identified sex in both the USA cohort (AUROC 0.943 (0.942-0.943)) and UKB datasets (n = 42,386, AUROC 0.971 (0.969-0.972)). In explainability analyses we found QRS duration, T wave morphology, QT interval, heart rate and QRS voltage as the most important factors in contributing to AI-ECG sex identification. In females only but not in males, sex discordance score was associated with a covariate-adjusted increased risk of cardiovascular death in outpatients with normal ECGs from the USA cohort, (Females hazard ratio (HR) 1.64 (1.18-2.29) p = 0.003, Males HR 1.04 (0.66-1.63), p = 0.86). This pattern persisted in the UKB: Females HR 1.39 (1.08-1.78) p = 0.01, Males HR 0.97 (0.77-1.22), p = 0.80, Fig 1). In phenome-wide association studies, we found females with a higher sex score discordance were more likely to have heart failure or myocardial infarction. Covariate-adjusted cox models confirmed the association of sex score discordance with increased future heart failure (HR 1.21 (1.07-1.37) p = 0.002 and future myocardial infarction (HR 1.32 (1.11-1.56) p = 0.001). In age- and body size-adjusted analyses, females with higher sex discordance score had increased left ventricular mass, and chamber volumes as well as increased muscle mass, reduced body fat percentage (Fig 2). In a genome-wide association study of sex discordance score we identified variants adjacent to IGF1R and NDRG4 in females, which have been previously associated with LV mass and sex hormone levels (Fig 2). Conclusion We describe sex discordance score as a novel AI-ECG biomarker capable of identifying females with disproportionately elevated cardiovascular risk. Sex discordance score may help uncover potential underlying mechanisms of cardiovascular disease among females, and future clinical studies are needed to determine its potential utility in identification of females at higher risk of cardiovascular events. Rather than exacerbating biases, AI-ECG has the potential to reduce female cardiovascular health inequalities.

Integrity of central nervous autonomous tracts is associated with cardiac function, cardiovascular risk factors, organ damage and major adverse cardiovascular events

Abstract Background Alterations in the central autonomic nervous system have been linked to the pathogenesis of cardiovascular (CV) risk and disease. Moreover, these conditions are treatable by pharmacological or interventional modification of the activity of the autonomic nervous system. Purpose The UK Biobank enables the investigation of the relationship between changes in the CAN and CV function or disease within a large population. Microstructural integrity of the CAN was assessed for associations with cardiac function, CV risk and damage representations, and major adverse cardiovascular events (MACE). Method Microstructural diffusion metrics for 7 CAN tracts were estimated using a Bayesian approach, which determines the three components of a standard white matter-based tissue model: 1. the free water fraction (CSF); 2. the fraction within neuronal processes, i.e. axons and dendrites (INTRA); and 3. the fraction outside of axons or dendrites (EXTRA), representing the cellular compartment and the extracellular matrix. Volume fractions of the three microstructural components were analysed for associations with cardiac index, blood pressure, CV target organ damage (arterial stiffness, left ventricular mass, and wall thickness), and MACE, using covariate-adjusted regression models that corrected for multiple comparisons. Results Analysis of cardiac function in 26,302 participants revealed significant associations between cardiac index and CAN regions in the cortical and subcortical networks. Arterial stiffness was significantly associated with markers of microstructural integrity in the cortical networks only (n=22,491), while systolic (n=34,114) and diastolic blood pressure (n=34,130), left ventricular mass (n=22,491) and wall thickness (n=22,491) showed extensive associations with the cortical and subcortical CAN. MACE (n=33,444) was associated with cortical markers of microstructural integrity of the CAN in limbic pathways (significant CANs all p&amp;lt;0.002) and the CAN pathways connecting cortical areas (significant CANs left all &amp;lt;0.001, right=0.001). The observed pattern of microstructural metrics suggests that the integrity of neural connections (intra-fraction) positively correlates with adverse outcomes, while an increase in free fluid (CSF) volume was typically associated with a negative impact. Conclusion In this analysis, markers of CAN integrity and degradation showed extensive associations with indicators of CV function, risk factors, damage parameters, and outcomes. This evidence supports the crucial role of autonomic regulation in cardiovascular disease. Future research is needed to determine whether these associations indicate harmful processes, such as neuroinflammation, contributing to cardiovascular (CV) risk and disease development, or if they are consequences of pre-existing elevated risk factors or events.CANs associated with MACEAssociations of CAN with CV organ damage

Participation, barriers, facilitators and bullying experiences of trans people in sport and fitness: findings from a national community survey of trans people in Australia.

This study aimed to assess participation rates of transgender and gender diverse (trans) people in sport/fitness activities, compare mental health outcomes for trans people participating in sport/fitness with those who do not and explore internal/external barriers and bullying experiences faced by trans people in sport/fitness contexts. A cross-sectional online survey open to trans people aged ≥16 years living in Australia was conducted between February and April 2023 and it assessed rates of sport/fitness participation, barriers to participation and bullying experiences through multiple-choice questions. Mental health measures comprised the Kessler Psychological Distress Scale (K10) and self-reported history of self-harm and suicidality. Covariate-adjusted binary logistic regression models tested associations between interpersonal factors, sport/fitness variables and mental health outcomes. Of 664 respondents (median age 32 years), around one-third (32.8%) regularly participated in sport/fitness. Common internal barriers to participation included anxiety about others' reactions (63.9%), body dissatisfaction/dysphoria (56.5%) and fears about feeling accepted/affirmed by others (54.7%). Respondents commonly reported experiencing inadequate bathroom/changing facilities (44.4%), exclusionary rules and regulations surrounding gender (36.7%), and invasive or uncomfortable policies or procedures (23.3%). Over one-third (34.4%) of trans people had experienced gender-based bullying or exclusion. Regular sport/fitness participation was associated with significantly lower K10 scores (mean difference=-4.4, 95% CI-5.8, -2.9, p<0.001) and a 40% reduction in odds of recent thoughts of self-harm and suicide (aOR 0.6, 95% CI 0.5, 0.9, p=0.01; aOR 0.6, 95%CI 0.4, 0.9, p=0.02). Trans people face significant barriers to sport/fitness despite experiencing significant mental health and personal benefits from participation. Affirming and including trans people in sport and fitness should be a key priority for sport and fitness federations, organisations and policy-makers.

Visit-to-visit changes in heart rate in heart failure: A pooled participant-level analysis of the PARADIGM-HF and PARAGON-HF trials.

Resting heart rate (HR) is a strong risk marker in patients with heart failure (HF), but the clinical implications of visit-to-visit changes in HR (ΔHR) are less well established. We aimed to explore the association between ΔHR and subsequent outcomes in a pooled dataset of two well-characterized cohorts of patients with HF across the full range of left ventricular ejection fraction (LVEF). PARADIGM-HF and PARAGON-HF were randomized trials testing sacubitril/valsartan versus enalapril or valsartan, respectively, in patients with HF and LVEF ≤40% (PARADIGM-HF) or LVEF ≥45% (PARAGON-HF). We analysed the association between ΔHR from the preceding visit with the primary endpoint of HF hospitalization (HFH) or cardiovascular death using covariate-adjusted Cox proportional hazards models. A total of 13 194 patients (mean age 67 ± 11 years, 67% men, mean LVEF 40 ± 15%) were included. Over a median follow-up of 2.5 years, 3114 patients experienced a first HFH or cardiovascular death event (10.4 events per 100 patient-years). An increase in HR from the preceding visit, compared with no change, was associated with a higher risk (hazard ratio 1.12; 95% confidence interval [CI] 1.10-1.15; p < 0.001 per 5 bpm increase). Conversely, a drop in HR was associated with a lower risk (hazard ratio 0.97; 95% CI 0.94-1.00; p = 0.044 per 5 bpm drop). The prognostic implications of ΔHR were consistent across the range of LVEF and observed regardless of β-blocker use or presence of a permanent pacemaker. Visit-to-visit increases in HR were especially prognostic in patients without atrial fibrillation (pinteraction = 0.006). Across a broad spectrum of patients with chronic HF, increases in HR from a preceding visit independently predicted clinical outcomes. The detection of notable increases in HR between outpatient visits may help identify patients at heightened risk of adverse events. Clinical Trial Registration; ClinicalTrials.gov NCT01035255 (PARADIGM-HF), NCT01920711 (PARAGON-HF).

A longitudinal path model examining the transactional nature of parenting and child externalizing behaviors in a large, sociodemographically diverse sample.

Children's externalizing behaviors are associated with impairments across the lifespan. Developmental psychopathology theories propose transactional (bidirectional) associations between child externalizing behaviors and parenting during childhood and adolescence. Yet, these foundational relations in early childhood are not well-studied. Utilizing a large, mixed-sex sample, we examined the reciprocal nature of parenting and child externalizing behaviors across early childhood using robust repeated-measures models. Repeated measures data were drawn from a socioeconomically diverse, longitudinal pregnancy cohort of 1287 (64% Black, 31% White) mother-child dyads at four time points (ages one to six). Three variables were included in cross-lagged panel models: observed parenting quality, child externalizing symptoms, and a maternal risk composite. In covariate-adjusted models, higher parenting quality at Wave 1 predicted lower child externalizing symptoms at Wave 2. Higher externalizing symptoms at Wave 1 and Wave 2 predicted lower parenting quality at Wave 2 and Wave 3, respectively. Maternal risk and parenting quality were not significantly associated. Findings showed both parent-driven and child-driven effects across early childhood that did not vary by child sex. The transactional nature of the parent-child relationship begins in infancy, underscoring the importance of early screening and provision of supports for families to minimize and prevent the development of serious psychopathology.

Finding benefits during collective stress: A study of health behaviors in a longitudinal representative U.S. sample during the COVID-19 era.

Cognitive strategies like finding benefits during adversity may facilitate coping during collective stressors (like COVID-19) by reducing distress or motivating health protective behaviors. We explored relationships between benefit finding, collective- and individual-level adversity exposure, psychological distress, and health protective behaviors using longitudinal data collected during the COVID-19 era from a representative, probability-based sample of U.S. residents: Wave 1 (N = 6,514, March 18, 2020-April 18, 2020, 58.5% completion rate); Wave 2 (N = 5,661, September 26, 2020-October 16, 2020, 87.1% completion rate); Wave 3 (N = 4,881, November 8, 2021-November 24, 2021, 75.3% completion rate); and Wave 4 (N = 4,859, May 19, 2022-June 16, 2022, 75.1% completion rate). Benefit finding was common; k-means clustering (an exploratory, data-driven approach) yielded five trajectories: always high (15.85%), always low (18.52%), always middle (28.47%), increasing (17.79%), and decreasing (19.37%). Benefit-finding trajectories were generally not strong correlates of psychological distress and functional impairment over time. Rather, benefit finding robustly correlated with health protective behaviors relevant to COVID-19 and the seasonal flu. In covariate-adjusted models, benefit finding positively correlated with more social distancing (β = .24, p < .001) and mask wearing (β = .18, p < .001) at Wave 2 and greater COVID-19 (odds ratio, OR = 1.23, p = .001) and flu (OR = 1.29, p < .001) vaccination at Wave 3. Although benefit finding was not generally associated with lower psychological distress during a collective stressor, it correlated with engagement in stressor-related health protective behaviors. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The association between hunger-coping economic tradeoffs and food insecurity among female recipients of charitable food assistance

Food insecurity is an indicator of well-being in the United States. A high proportion of recipients of charitable food assistance (CFA) are women and are often in charge of specific household managerial responsibilities (e.g., childcare, transportation). Consequently, they frequently face choices between paying for food and paying for other basic need(s). This study aims to examine which hunger-coping economic tradeoffs place females with at least one dependent child in the house and females without a dependent child in the house at risk for experiencing food insecurity. Data was collected at 10 Houston-area and 10-Atlanta-area food pantries in 2022 (N=883). Using USDA cutoff criteria, households were considered food insecure based on ≥3 affirmative responses to the 18-item Food Security Scale Module. Hunger-coping economic tradeoff experiences were based on affirmative responses to whether anyone in the household ever had to choose between food and six basic needs (i.e. childcare, medicine/medical care, utilities, rent/mortgage, transportation, education). Covariate-adjusted logistic regression models were conducted to understand the relationship between six hunger-coping economic tradeoffs and food insecurity for the entire analytic sample and stratified by whether the female participant had a child in house. Standard errors in all regression models were corrected to account for multiple observations within a pantry. Adults, on average, were 55 years old (58% food insecure; 47% Hispanic; 42% black). Four hunger-coping economic tradeoffs were related to experiencing food insecurity. Economic tradeoffs between food and a) medicine/medical care and b) transportation elevated the likelihood of food insecurity, regardless of child status. Tradeoffs between food and childcare increased the risk for experiencing food insecurity among females with a dependent child. Deciding to pay between food and utilities was related to food insecurity experiences among females without a dependent child. Increases in Supplemental Nutrition Assistance Program (SNAP) benefits and eligibility along with programs to enhance resources related to medical care, transportation, childcare and utilities could help reduce food insecurity, especially among CFA recipients.

Adolescents’ mental health is associated with food parenting practices among British Columbian families

BackgroundAdolescence is a developmental period marked by significant changes related to the body and food parenting practices. However, few studies have explored child-level psychological correlates of these practices during adolescence. Our study examined whether adolescents’ weight status, weight concerns, self-esteem, and anxiety were associated with food parenting practices, and whether these associations significantly differ by adolescents’ gender among 297 families in British Columbia, Canada. MethodsParents (47 years, 76% mothers) completed a food parenting practice item bank. Adolescents (14 years, 52% girls) self-reported their height and weight, weight concerns, self-esteem, and anxiety. Covariate-adjusted regression models evaluated the association of adolescents’ weight and mental health with nine practices (main effects). Interactions were used to evaluate the moderating role of gender, and further decomposed in all models to examine simple effects within each gender group. ResultsMain-effect models showed positive associations between: (1) weight concerns and child involvement, (2) weight concerns and accommodating practices, (3) self-esteem and healthy eating opportunities, and (4) self-esteem with meal routines, as well as negative associations between: (5) self-esteem and accommodating practices, (6) self-esteem and coercive control, and (7) anxiety and rules and limits. In all models (except one) interactions with gender were not significant; however, in all cases the decomposed effects showed only significant effects among girls. A significant gender interaction emerged in (8) the association between anxiety and coercive control, but the decomposed effects were not significant for either gender. Adolescents’ weight status was not associated with food parenting practices in any model. ConclusionsFood parenting practices are associated with mental health indicators among British Columbian families; however future studies should examine multidirectional relationships between these practices, adolescents’ mental health, and eating habits.

Mediterranean-DASH Diet Intervention for Neurodegenerative Delay Diet and Psychological Problems in Maintenance Hemodialysis Patients by the Structural Equation Modeling Analysis of Malnutrition and Inflammation Markers Approach

ObjectiveAlthough it is known that diet quality affects psychological problems in hemodialysis patients, there is need to explain the role of modifiable risk factors in this relationship. Therefore, the aim of this study was a) to investigate the relationship between diet quality and modifiable risk factors to depression and anxiety in end-stage renal disease (ESRD) patients receiving maintenance hemodialysis; b) to explore the mediating roles of modifiable factors in the relationship with diet quality to depression and anxiety. MethodsThis cross-sectional study included 216 patients with ESRD receiving maintenance hemodialysis treatment. We assessed participants' dietary records for Mediterranean-DASH Diet Intervention for Neurodegenerative Delay (MIND) quality, Global Leadership Initiative on Malnutrition (GLIM) criteria for malnutrition and Hospital Anxiety and Depression (HAD)-scale for psychological problems. Furthermore, biochemical findings and anthropometric measurements were performed to evaluate nutritional markers, metabolic risk factors and inflammation. We applied hierarchical regression analysis to estimate modifiable risk factors for depression and anxiety and Structural-Equation-Modeling analysis to determine the mediating role of modifiable risk factors between diet quality and psychological problems. ResultsDepression symptoms were observed in 59.2% (n=128) of the participants, whilst the rate was 35.1% (n=76) for anxiety. Depression and anxiety were found to be negatively correlated with MIND levels after covariate adjusting model, and the rates of explanation were found to be 16.2% and 12.2%, respectively. C-reactive protein (CRP), albumin levels and the presence of malnutrition were shown to be significant predictors of depression (ΔF=14.761 and ΔR2:0.071 for covariate-adjusted model). Albumin levels, CRP, hemodialysis duration, and malnutrition were found to be independent predictors of anxiety (ΔF=16.174 and ΔR2:0.077 for covariate-adjusted model). It was found that CRP and malnutrition partially mediated the association of MIND score with depression, and CRP mediated the association with anxiety. ConclusionIt was concluded that adherence to the MIND diet is associated with a better nutritional profile and reduced inflammation, which in turn may be linked to fewer psychological problems.These further studies are needed to validate and expand upon our findings.

Competencies for health-enhancing physical activity are associated with body mass: results of an updated data pooling across 18 samples.

Although previous studies have illuminated associations between body mass and physical activity (PA), there have been scant insights regarding the physical, cognitive, and motivational determinants of PA in relationship to body mass. This study aimed to model courses of competencies for health-enhancing PA across the spectrum of BMI. We used cross-sectional data of 3670 individuals (mean [SD]: BMI, 25.54 [5.71] kg/m2; age, 46.11 [14.96] years) from a large data pooling with 18 primary samples employing the PA-related health competence (PAHCO) instrument. ANCOVA determined differences in 10PAHCO indicators by BMI categories (underweight, normal weight, overweight, and obesity). Covariate-adjusted multilevel models described the nonlinear courses of the PAHCO indicators across the BMI spectrum. The levels of all 10PAHCO indicators differed significantly among the BMI categories (F ≥ 14.8; p < 0.001). All competencies for health-enhancing PA could be best described by cubic functions having their maximum around normal weight while regressing with underweight and with increasing grades of obesity (0.02 ≤ ≤ 0.31). This study adds to associations between BMI and PA levels by specifying individuals' multidimensional requirements for health-enhancing PA. The present findings call for an integration of physical, motivational, and cognitive factors in practices of PA promotion and sustainable obesity treatment.

Effects of physically active maths lessons on children's maths performance and maths-related affective factors: Multi-arm cluster randomized controlled trial.

Physical activity (PA) may benefit academic performance, but it is unclear what kind of classroom-based PA is optimal for learning. We studied the effects of physically active maths lessons on children's maths performance and maths-related effects, and whether gender and previous mathematical or motor skills modify these effects. A total of 22 volunteered teachers and their pupils with signed consent (N = 397, mean age: 9.3 years, 51% females) participated in a 5-month, teacher-led, multi-arm, cluster-randomized controlled trial. The intervention included a PAL group (20 min of physically active learning in each 45-min lesson), a breaks group (two 5-min PA breaks in each 45-min lesson) and a control group (traditional teaching). Maths performance was assessed with a tailored curriculum-based test. Maths-related enjoyment, self-perceptions and anxiety were measured with a self-reported questionnaire. The individual-level intervention effects were tested via covariate-adjusted linear mixed-effect models with school classes serving as random effects. Changes in maths performance or self-perceptions did not differ between the intervention groups. Maths anxiety in learning situations increased in the PAL group (effect .28, 95% CI = .01-.56); there was no change in the other groups. Subgroup analyses suggested that maths anxiety increased in the PAL group among children in the two lowest tertiles of motor skills. It decreased in the highest tertile. Enjoyment decreased in the breaks group among pupils in the lowest motor skill tertile. Physically active maths lessons did not affect maths performance or self-perceptions but had divergent effects on maths anxiety and enjoyment, depending on motor skills.

Association of Electrocardiogram Findings With Clinical Outcomes in Patients With Chronic Coronary Syndrome: An Analysis of the ISCHEMIA Trials

ObjectiveWe aimed to investigate the association of electrocardiogram (ECG) findings with outcomes in patients with chronic coronary syndrome. MethodsThis secondary analysis of the ISCHEMIA and ISCHEMIA-CKD trials divided patients with chronic coronary syndrome into two groups, those with a normal ECG tracing and abnormal ECG tracing. Repolarization abnormalities included ST-segment depression ≥ 0.5 mm and T-wave inversion ≥ 1 mm; conduction abnormalities included left and right bundle branch block (LBBB and RBBB). The primary endpoint was cardiovascular death. Outcomes were assessed using a covariate-adjusted Cox-regression model. ResultsOf 5876 patients, 2901 (49.4%) had a normal and 2975 (50.6%) an abnormal ECG tracing. An abnormal ECG tracing at baseline, compared with a normal ECG tracing, was associated with an increased risk of cardiovascular death (257 of 2975 [8.6%] vs. 97 of 2901 [3.3%], adjusted hazard ratio [aHR] 2.01, 95% CI 1.58-2.55) over a median follow-up period of 3.1 years (IQR 2.1-4.2). This finding was consistent across subgroups except for patients with black skin color and current smokers, in whom an abnormal ECG was not significantly associated with increased risk of cardiovascular death. Individual ECG abnormalities (ST-segment depression [aHR 2.0, 95% CI 1.52-2.63], T-wave inversion [aHR 1.89, 95% CI 1.40-2.54], LBBB [aHR 1.74, 95% CI 1.05-2.90], and RBBB [aHR 1.52, 95% CI 1.04-2.22]) were independently associated with an increased risk of cardiovascular death. ConclusionIn patients with chronic coronary syndrome, an abnormal ECG tracing was associated with an increased risk of cardiovascular death. Our findings underscore the importance of the ECG in cardiovascular risk stratification and prognostication. Trial RegistrationNCT01471522, BioLINCC ID 14539.

Correlates of cannabis use and cannabis use disorder among adolescents with major depressive disorder and bipolar disorder in the National Comorbidity Survey-Adolescent Supplement (NCS-A)

BackgroundDespite evidence regarding prevalence and correlates of cannabis use (CU) and cannabis use disorder (CUD) in major depressive disorder (MDD) and bipolar disorder (BD) in adults, little is known about this topic among adolescents. MethodsData is from the 2001–2004 National Comorbidity Survey–Adolescent Supplement, an in-person, cross-sectional epidemiologic survey of mental disorders. Participants included adolescents, ages 13–18 years, with MDD (n = 354 with CU, n = 70 with CUD, n = 688 with no CU), BD (n = 79 with CU, n = 32 with CUD, n = 184 with no CU), or adolescents without mood disorders (n = 1413 with CU, n = 333 with CUD, n = 6970 with no CU). Analyses examined prevalence and correlates of CU and CUD within MDD and BD groups. ResultsCU was most prevalent in adolescents with MDD followed by adolescents with BD then controls. CUD was most prevalent in adolescents with BD followed by adolescents with MDD then controls. In covariate-adjusted ordinal logistic regression models, within MDD and BD, CU and CUD groups had significantly higher odds of lifetime suicidal ideation/attempts, as well as other significant indicators of clinical severity. LimitationsBased on changes in cannabis acceptance, potency, and availability in the two decades since this study was conducted, present findings may underestimate adverse cannabis associations. ConclusionCU and CUD are both associated with adverse clinical characteristics in a community-based sample of adolescents with MDD and BD. Evidence that risks of cannabis use extend across the spectrum of use is important for adolescents with MDD and BD, in whom cannabis-related consequences tend to be more severe.

Hospital readmission for acute kidney injury is independently associated with de novo end-stage renal disease after liver transplantation.

End-stage renal disease (ESRD) after liver transplantation (LT) is associated with high morbidity and mortality. The consequences of hospitalizations for post-LT acute kidney injury (AKI) are poorly understood. Using linked Medicare claims and transplant registry data, we analyzed adult liver alone recipients not receiving pre-transplant dialysis between 1/1/2007-12/31/2016. Covariate-adjusted Cox proportional hazards models stratified by center evaluated factors associated with AKI readmission during the first post-LT year, and whether AKI readmission was associated with de novo early (<1y) or late (≥1y) ESRD post-LT. The cohort included 10,559 patients and was 64.5% male, 72.5% White, 8.1% Black and 14.0% Hispanic with median age 62 years. Overall, 2,875 (27.2%) patients had ≥1 AKI hospitalization during the first year. eGFR at LT was associated with AKI readmission (aHR 1.16 per 10mL/min/1.73m2 decrease; p<0.001). The aHR for early ESRD in patients with ≥1 AKI readmission <90 days post-LT was 1.90 (p<0.001). The aHRs for late ESRD with 1 and ≥2 prior AKI readmissions were 1.57 and 2.80 respectively (p<0.001). AKI readmissions in the first post-LT year impact over one-quarter of recipients. These increase the risk of subsequent ESRD, but may represent an opportunity to intervene and mitigate further renal dysfunction.