Covariate-adjusted Analyses Research Articles

Good Friends and Good Neighbors: Social Capital and Food Insecurity in Families with Newborns

To examine the association between social capital and household food insecurity among US families with newborns. This cross-sectional analysis used enrollment data from 881 newborn-caregiver dyads at six geographically-diverse US academic sites enrolled in the Greenlight Plus Trial, a comparative effectiveness trial to prevent childhood obesity. Ordinal proportional-odds models were used to characterize the associations of two self-reported measures of social capital: 1) caregiver social support and 2) neighborhood social cohesion, with household food insecurity after controlling for sociodemographic characteristics. Among 881 newborn-caregiver dyads (49% Hispanic, 23% non-Hispanic white, 17% non-Hispanic Black; 49% with annual household income <$50,000), food security was high for 75%, marginal for 9%, low for 11% and very low for 4%. In covariate-adjusted analyses, caregivers with a low social support score of 18 had five times the odds (aOR=5.03 95%CI=3.28-7.74) of greater food insecurity compared with caregivers with a high social support score of 30. Caregivers with a low neighborhood social cohesion score of 10 had nearly three times the odds (aOR=2.87 95%CI 1.61-5.11) of greater food insecurity compared with caregivers with a high neighborhood social cohesion score of 20. These associations remained robust when both social capital measures were included in one model. Caregiver social support and neighborhood social cohesion each appear to be inversely associated with food insecurity among US families with newborns. Longitudinal research is needed to determine the directionality of these relationships and whether improving social capital for families with young children reduces household food insecurity.

Association of self-reported bruxism and academic performance in Jazan University dental students: A cross-sectional study

Aims: The purpose of this cross-sectional descriptive study was to investigate the association between self-reported bruxism and academic performance among dental students at Jazan University. Material and Methods: One hundred sixty-eight students (73 males and 95 females) were evaluated in this study, between the age groups of 18 years and above. Self-reported bruxism was measured by utilizing a customized questionnaire. Academic performance was analyzed using participants’ grade point average (GPA) for the year. Independent t-tests and one-way analysis of variance (ANOVA) were utilized to find the association between the self-reported bruxism and the covariate-adjusted analysis (CI 95%). The Spearmen correlation coefficient was utilized to find the correlation between the variables. Results: The reported prevalence of self-reported bruxism was 66.25% between both genders. Males (mean = 36.86) have lower bruxism scores compared to females (mean = 42.14), suggesting a potential gender-based difference in bruxism severity. A moderate positive correlation is observed between self-reported stress levels and bruxism scores (r = 0.268**, P &lt; 0.01), indicating that as stress levels increase, there is a tendency for bruxism scores to also increase. A weak negative correlation is observed between academic performance and bruxism scores (r = -0.034, P &gt; 0.05), suggesting a minimal association between academic performance and bruxism severity. However, bruxism score was higher among females with higher GPA. Conclusions: This study demonstrated a weak negative association between self-reported bruxism and academic performance. It was noteworthy that females with higher GPA and low socioeconomic status had higher bruxism scores compared to males.

Multicomponent family support intervention in intensive care units: statistical analysis plan for the cluster-randomized controlled FICUS trial

The FICUS trial is a cluster-randomized superiority trial to determine the effectiveness of a nurse-led, interprofessional family support intervention (FSI) on the quality of care, family management and individual mental health of family members of critically ill patients, compared to usual care. This paper describes the statistical analysis plan of the FICUS trial. The primary outcome is quality of family care, assessed by the Family Satisfaction in ICU Questionnaire (FS-ICU-24R) at patient discharge from the ICU. Several secondary outcomes are additionally assessed 3, 6, and 12 months thereafter. Sixteen clusters (ICUs) were randomly assigned 1:1 to FSI or usual care using minimization (8 per treatment). The target sample size is 56 patients per cluster (896 in total). Recruitment has been completed in January 2024. The follow-up of the last participant will be completed in early 2025. The primary and secondary outcomes will be analyzed by linear mixed-effects models (LMM). The main model for the primary outcome will include a random intercept per cluster with treatment (FSI vs. usual care) as the only explanatory variable due to the relatively small number of clusters. In addition, covariate-adjusted analyses will be conducted, including two cluster-level characteristics used in the minimization as well as participant-level characteristics. Moreover, a number of subgroup analyses by cluster- and participant-level characteristics are pre-specified.Trial registration ClinicalTrials.gov NCT05280691. Registered on February 20, 2022.

GLIM criteria-based identification of severe malnutrition and its relationship with the risk of mortality among older Chinese adults with arthritis or rheumatism

BackgroundMalnutrition is a well-known risk factor for mortality among older adults. Arthritis and rheumatism are characterized by chronic inflammation and are also related to malnutrition as diagnosed using the Global Leadership Initiative on Malnutrition (GLIM) criteria. This study was thus developed to examine the associations linking malnutrition and all-cause death among older adults in China, employing the GLIM criteria to assess malnutrition.MethodsTwo waves of the China Health and Retirement Longitudinal Study from 2013 and 2018 were used to conduct this study. Moderate malnutrition was defined as low BMI (< 18.5 and < 20 for individuals < 70 and 70 + years of age, respectively), an unintended 10–20% decrease in weight, or low muscle mass based on the sex-specific lowest 20% of the height-adjusted muscle mass as < 5.039 kg/m2 in women and < 6.866 kg/m2 in men. Severe malnutrition was defined as a > 20% unintended decrease in weight only or the combination of both low muscle mass and an unintended reduction of over 10% in weight. Associations between malnutrition and the risk of all-cause death were assessed through Cox regression analyses.ResultsOverall, this study enrolled 1766 subjects 60 + years of age, of whom 57.36% (1033/1766) were female. Malnutrition was estimated to affect 418 (23.67%) of these individuals at baseline, with 21.06% and 2.60% affected by moderate and severe malnutrition, respectively. Over the 5-year follow-up, 189 of these individuals died. Covariate-adjusted Cox regression analyses confirmed a significant association between severe malnutrition and the risk of death in this cohort (HR = 2.196, 95%CI 1.125–4.286, P = 0.021).ConclusionsSevere malnutrition, identified through screening based on the GLIM criteria, was associated with an increased risk of all-cause death among older Chinese adults with arthritis or rheumatism.

Association of Limited Health Literacy With Clinical and Patient-Reported Outcomes in Individuals With Systemic Lupus Erythematosus.

Health literacy is an important social determinant of health, with limited health literacy associated with worse health outcomes. This study examined the associations between limited health literacy with patient-reported outcomes and disease activity/damage among 267 Black women with active systemic lupus erythematosus (SLE) enrolled in the Peer Approaches to Lupus Self-Management (PALS) program. The three-item Chew Health Literacy Screening was used to dichotomize those reporting in the "limited" range on any item with outcomes compared via generalized linear models. Baseline surveys and assessments obtained at study entry as part of the PALS study were used. Primary outcomes included disease activity and lupus damage; other secondary outcomes included patient activation, self-efficacy, physician/patient communication, and quality of life. The study included 267 Black women with SLE. In covariate-adjusted analyses, participants with limited health literacy (88 [33%]) were more likely to have lower patient activation (Patient Activation Measure P < 0.0001), lower self-efficacy (Lupus Self-Efficacy P < 0.0001), higher lupus damage (self-administered Brief Index of Lupus Damage P=.016), higher disease activity (Systemic Lupus Activity Questionnaire symptom severity P=0.006), and worse physician/patient communication (patient-centered care P < 0.0001) compared to those with adequate health literacy. Those with limited health literacy also reported worse lupus quality of life (P=0.0004) and greater levels of stress (Perceived Stress Scale-4 P < 0.0001) and were 2.4 times more likely to have probable major depression (Patient Health Questionnaire Depression Scale-8 of ≥10 P=0.004) and probable anxiety disorder (General Anxiety Disorder-7 of ≥10 P=0.007) compared to those with adequate health literacy. Black women with SLE and limited health literacy have worse clinical outcomes and represent a particularly vulnerable population with significantly disparate health outcomes. These findings suggest health literacy and complexities of managing SLE may impair clinical care in multiple domains, ultimately contributing to higher disease activity and death/damage, and are important to address in clinical care and future interventions in patients with SLE.

Aripiprazole as protector against COVID-19 mortality

The relation of antipsychotics with severe Coronavirus Disease 19 (COVID-19) outcomes is a matter of debate since the beginning of the pandemic. To date, controversial results have been published on this issue. We aimed to prove whether antipsychotics might exert adverse or protective effects against fatal outcomes derived from COVID-19. A population-based retrospective cohort study (January 2020 to November 2020) comprising inpatients (15,968 patients) who were at least 18 years old and had a laboratory-confirmed COVID-19 infection. Two sub-cohorts were delineated, comprising a total of 2536 inpatients: individuals who either had no prescription medication or were prescribed an antipsychotic within the 15 days preceding hospitalization. We conducted survival and odds ratio analyses to assess the association between antipsychotic use and mortality, reporting both unadjusted and covariate-adjusted results. We computed the average treatment effects, using the untreated group as the reference, and the average treatment effect on the treated, focusing solely on the antipsychotic-treated population. Among the eight antipsychotics found to be in use, only aripiprazole showed a significant decrease in the risk of death from COVID-19 [adjusted odds ratio (OR) = 0.86; 95% CI, 0.79–0.93, multiple-testing adjusted p-value < 0.05]. Importantly, these findings were consistent for both covariate-adjusted and unadjusted analyses. Aripiprazole has been shown to have a differentiated beneficial effect in protecting against fatal clinical outcome in COVID-19 infected individuals. We speculate that the differential effect of aripiprazole on controlling immunological pathways and inducible inflammatory enzymes, that are critical in COVID19 illness, may be associated with our findings herein.

Association of prediabetes with clinical outcomes in patients with chronic coronary syndrome: a post hoc analysis of the ISCHEMIA and ISCHEMIA-CKD trials

BackgroundThere is conflicting evidence whether prediabetes is associated with adverse clinical outcomes in patients with chronic coronary syndrome. We aimed to assess the effect of prediabetes in patients with chronic coronary syndrome on clinical outcomes.MethodsThis is a secondary analysis of data from the ISCHEMIA and ISCHEMIA-CKD trials, including patients with chronic coronary syndrome determined by coronary computed tomography angiography or exercise-stress testing. Participants were assigned to the normoglycemia group (HbA1c < 5.7% [< 39 mmol/mol]), prediabetes group (HbA1c 5.7–6.4% [40–47 mmol/mol]), or diabetes group (HbA1c ≥ 6.5% [≥ 48 mmol/mol]). The primary end point of this study was all-cause mortality. Secondary endpoints included major adverse cardiovascular events and composites thereof.ResultsOverall, the primary endpoint all-cause mortality occurred in 330 (8.4%) of 3910 patients over a median follow-up time of 3.1 years (IQR 2.1–4.1). The primary endpoint all-cause mortality occurred in 37 (5.2%) of 716 patients in the normoglycemia group, in 63 (6.9%) of 911 in the prediabetes group, and in 230 (10.1%) of 2283 in the diabetes group. In the covariate-adjusted Cox model analysis, the estimated adjusted HR (aHR) in the prediabetes group as compared with the normoglycemia group was 1.45 (95%CI, 0.95–2.20). The aHR in the diabetes group as compared with the normoglycemia group was 1.84 (95%CI, 1.29–2.65). Prediabetes, compared with normoglycemia, was associated with an increased risk of stroke (aHR, 3.44, 95%CI, 1.15–10.25). Subgroup analyses suggested an increased risk of all-cause death associated with prediabetes in males and patients under 65 years.ConclusionsIn patients with chronic coronary syndrome, diabetes but not prediabetes was associated with significantly increased risk of all-cause death within a median follow-up period of 3.1 years.Trial Registration NCT01471522, BioLINCC ID 13936.

Impact of Propofol Exposure on Neurocognitive Outcomes in Children With High-Risk B ALL: A Children's Oncology Group Study.

Many children treated for ALL develop long-term neurocognitive impairments. Increased risk of these impairments is associated with treatment and demographic factors. Exposure to anesthesia is an additional possible risk factor. This study evaluated the impact of cumulative exposure to anesthesia on neurocognitive outcomes among a multicenter cohort of children with ALL. This study was embedded in AALL1131, a Children's Oncology Group phase III trial for patients with high-risk B-ALL. In consenting patients age 6-12 years, prospective uniform assessments of neurocognitive function were performed during and at 1 year after completion of therapy. Exposure to all episodes of anesthetic agents was abstracted. Multivariable linear regression models determined associations of cumulative anesthetic agents with the primary neurocognitive outcome reaction time/processing speed (age-normed) at 1 year off therapy, adjusting for baseline neurocognitive score, age, sex, race/ethnicity, insurance status (as a proxy for socioeconomic status), and leukemia risk group. One hundred and forty-four children, 76 (52.8%) males, mean age of 9.1 (min-max, 6.0-12.0) years at diagnosis, underwent a median of 27 anesthetic episodes (min-max, 1-37). Almost all patients were exposed to propofol (140/144, 97.2%), with a mean cumulative dose of 112.3 mg/kg. One year after therapy, the proportion of children with impairment (Z-score ≤-1.5) was significantly higher compared with a normative sample. In covariate-adjusted multivariable analysis, cumulative exposure to propofol was associated with a 0.05 Z-score decrease in reaction time/processing speed per each 10 mg/kg propofol exposure (P = .03). In a multicenter and uniformly treated cohort of children with B-ALL, cumulative exposure to propofol was an independent risk factor for impairment in reaction time/processing speed 1 year after therapy. Anesthesia exposure is a modifiable risk, and opportunities to minimize propofol use should be considered.

Abstract 3471: Predictors of cancer related distress among patients with colorectal cancer

Abstract Background: Colorectal cancer (CRC) incidence among patients under age 50 has increased drastically over the past few decades. Given that increased cancer-related distress is associated with worse oncologic outcomes, studies are needed to assess the psychosocial wellbeing of CRC survivors across the shifting demographic and socioeconomic landscape. Methods: The ColoCare Study is a prospective cohort study of newly-diagnosed CRC patients enrolled across six US and European sites. We analyzed ColoCare data from the Washington University site, which has high accrual of Non-Hispanic Black (NHB) patients. Cancer-related distress was measured using a validated Cancer and Treatment Distress (CTXD) tool with 4-point Likert scales ranging from 0-3 with higher scores indicating greater distress. Covariate-adjusted linear regression analyses were used to evaluate sociodemographic, lifestyle, and clinical factors as predictors of cancer-related distress 12 months following CRC diagnosis. Results: This analysis included 156 participants enrolled from April 2017 to September 2022 who completed a 12-month CTXD questionnaire: 51.4% male; mean age 55.3 (SD 13.1) years; 64.8% Non-Hispanic White; 33.1% NHB; mean 12-month CTXD score 0.75 (SD 0.70). In covariate-adjusted models, predictors of increased distress at 12 months (Table 1) included recurrence or new metastasis (regression coefficient (β)=0.63, 95% confidence interval (CI)=0.35-0.91), stage II ((β=0.49, 95% CI=0.15-0.84) or stage III (β=0.37, 95% CI=0.02-0.72) disease, current smoking (β=0.33, 95% CI=0.10-0.56), female gender (β=0.22, 95% CI=0.00-0.44) and age (β= -0.01, 95% CI -0.02-0.00). Race and social vulnerability index were not predictors of distress in this analysis. Conclusion: Among CRC survivors, those with younger age, female gender, active smoking, advanced stage, and disease progression may benefit from targeted cancer-related distress assessment and interventions. Multiple Linear Regression Analysis Estimating 12-Month CTXD Scores Variable Regression Coefficients 95% Lower CI 95% Upper CI P-value Age -0.01 -0.02 0.00 *0.015 Gender: Female vs. Male 0.22 0.00 0.44 *0.050 Race: Black vs. White 0.01 -0.26 0.29 0.933 Race: Other vs. White -0.17 -0.91 0.57 0.650 Social Vulnerability Index 0.15 -0.26 0.56 0.463 BMI 0.00 -0.02 0.02 0.908 Smoking Status: Current vs. Former/Never 0.33 0.10 0.56 *0.006 Stage II vs. Stage I 0.49 0.15 0.84 *0.006 Stage III vs. Stage I 0.37 0.02 0.72 *0.040 Stage IV vs. Stage I 0.41 -0.08 0.91 0.100 Neoadjuvant Treatment: Yes vs. No 0.09 -0.19 0.38 0.510 Adjuvant Treatment: Yes vs. No -0.23 -0.53 0.07 0.133 Stoma at 6 months: Yes vs. No -0.21 -0.68 0.25 0.364 Recurrence or New Metastasis: Yes vs. No 0.63 0.35 0.91 *&amp;lt;0.001 Citation Format: Catherine N. Zivanov, Rachel Kalbfell, Jorge Zarate Rodriguez, Shaleen Sathe, Joel Vetter, Myung Jeon, Dante Chao, Kerri A. Ohman, Jennifer Ose, Biljana Gigic, Erin M. Siegel, David Shibata, Christopher I. Li, Jane C. Figueiredo, Cornelia M. Ulrich, Adetunji T. Toriola. Predictors of cancer related distress among patients with colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3471.

Analysis of immune-related genes (IRGs) and their potential role in sexual dimorphism in patients (pts) with metastatic colorectal cancer (mCRC).

182 Background: Sex-based disparities have been reported for mCRC both in incidence, males having higher incidence than females, and in outcome, younger females having better outcome than males of same age or older females. Tumor immune microenvironment is hypothesized to have role in this sexual dimorphic pattern. Herein, we explored the role of gene expression (exp) and genetic variation of IRGs on progression-free (PFS) and overall survival (OS) in mCRC pts. Methods: 21 IRGs with potential roles in CRC were identified from literature review. The association of tumor gene exp with PFS and OS was evaluated in pts with mCRC (433 pts, RNA seq) from CALGB/SWOG 80405. Subgroup analyses were based on treatment (bevacizumab [bev] (N = 226) / cetuximab [cet] (N = 207)) and sex (male (N = 271) / female (N = 162)). Further, the impact on outcome of 5 selected germline single nucleotide polymorphisms (SNPs) in 3 significant IRGs, SCG2 (rs600257, rs9283537), CRIP2 rs66717274, and AXIN2 (rs7591, rs2240308), was evaluated in genotyped (OncoArray, Illumina) samples of 451 pts from 2 clinical trials: FIRE-3 (FOLFIRI-bev, N = 107; FOLFIRI-cet, N = 129) and TRIBE (FOLFIRI-bev, N = 215). Unadjusted associations were evaluated using log-rank (lr) tests; covariate-adjusted analyses were performed using Cox models for hazard ratio (HR) estimation and likelihood ratio testing. Results: Of 21 analyzed IRGs, SCG2, CRIP2 and AXIN2 significantly associated with PFS and OS in mCRC pts in CALGB/SWOG 80405 divided into tertiles of high, medium and low exp. Among pts receiving cet treatment, SCG2high (PFS: median 9.0 vs 13.0 months (mo), lrP = 0.015; OS: 20.4 vs 37.4 mo, lrP = 2.9e-05) and CRIP2high (PFS: 9.2 vs 14.2 mo, lrP = 0.00076; OS: 20.9 vs 36.3 mo, lrP = 8.3e-05) were significantly associated with shorter PFS and OS, whereas AXIN2high (PFS: 14.1 vs 7.3 mo, lrP = 2.4e-06; OS: 37.1 vs 15.6 mo, lrP = 4.9e-05) correlated with longer PFS and OS. Sex-based differences were observed, SCG2high exp associated with shorter PFS (10.0 vs 13.1 mo, lrP = 0.0054) and OS (22.3 vs 36.0 mo, lrP = 7.7e-05), and similarly CRIP2high associated with shorter PFS (9.8 vs 14.2 mo, lrP = 0.012) and OS (23.6 vs 35.8 mo, lrP = 4e-04), in males but not in females. In univariate SNP analysis, SCG2 rs9283537 any A allele showed shorter PFS (HR = 0.62, 95% Confidence interval [CI] = 0.40-0.98, P = 0.039) in females but longer PFS (HR = 2.37, 95% CI = 1.07-5.22, P = 0.028) in males compared to G/G carriers in the FIRE-3 cet cohort and interaction analysis showed significant p-values for PFS and OS (P&lt;0.005). Conclusions: Our results highlight important role for SCG2, CRIP2, and AXIN2 as prognostic and predictive biomarkers for first-line treatment in mCRC, with potential targeted agent- and pt’s sex-based differences. These biomarkers with further validation may contribute to personalized treatment strategies for mCRC pts.

MiMultiCat: A Unified Cloud Platform for the Analysis of Microbiome Data with Multi-Categorical Responses.

The field of the human microbiome is rapidly growing due to the recent advances in high-throughput sequencing technologies. Meanwhile, there have also been many new analytic pipelines, methods and/or tools developed for microbiome data preprocessing and analytics. They are usually focused on microbiome data with continuous (e.g., body mass index) or binary responses (e.g., diseased vs. healthy), yet multi-categorical responses that have more than two categories are also common in reality. In this paper, we introduce a new unified cloud platform, named MiMultiCat, for the analysis of microbiome data with multi-categorical responses. The two main distinguishing features of MiMultiCat are as follows: First, MiMultiCat streamlines a long sequence of microbiome data preprocessing and analytic procedures on user-friendly web interfaces; as such, it is easy to use for many people in various disciplines (e.g., biology, medicine, public health). Second, MiMultiCat performs both association testing and prediction modeling extensively. For association testing, MiMultiCat handles both ecological (e.g., alpha and beta diversity) and taxonomical (e.g., phylum, class, order, family, genus, species) contexts through covariate-adjusted or unadjusted analysis. For prediction modeling, MiMultiCat employs the random forest and gradient boosting algorithms that are well suited to microbiome data while providing nice visual interpretations. We demonstrate its use through the reanalysis of gut microbiome data on obesity with body mass index categories. MiMultiCat is freely available on our web server.

Anticoagulation dosage strategy therapy, length of stay, and all-cause mortality in critically ill COVID-19 patients admitted to the intensive care unit.

Few studies examined several anticoagulation (AC) dosage strategy therapies for various outcomes among coronavirus disease-2019 (COVID-19) patients. However, this AC dosage strategy therapy has not been investigated to assess the length of stay (LOS) and all-cause mortality among critically ill COVID-19 patients admitted to the intensive care unit (ICU), especially in the eastern province of Saudi Arabia. Thus, this study aimed to examine the association of AC dosage strategy therapy with the LOS and all-cause mortality among critically ill COVID-19 patients admitted to the ICU. We enrolled 170 patients aged 18 years or older, had a confirmed COVID-19, and were hospitalized in a tertiary care facility in the eastern province of Saudi Arabia between March 1, 2020, and January 31, 2021. Patients (n = 56) who received Enoxaparin at a dose of less than or equal to 5000 units of unfractionated heparin thrice daily were categorized as receiving a "prophylaxis" dose. Patients (n = 114) who received a therapeutic dose but not a prophylaxis dose were categorized as receiving a "therapeutic dose." The 30-day ICU LOS was the main outcome, while all-cause mortality was the secondary outcome. The covariate-adjusted logistic regression analysis revealed that the therapeutic dose was significantly associated with a 1.74-fold longer ICU LOS and 6.60-fold greater mortality risk than the prophylaxis dose. Critically ill COVID-19 patients who received the therapeutic dose had a longer ICU LOS and higher mortality than those who received the prophylaxis dose.

Comparisons of Percutaneous Ablation, Open or Laparoscopic Liver Resection for Barcelona Clinic Liver Cancer Stage 0-A Hepatocellular Carcinoma: A Concurrent Generalized Propensity Score Analysis.

Liver resection and ablation remain the most common therapeutic options for Barcelona Clinic Liver Cancer (BCLC) stage 0-A hepatocellular carcinoma (HCC), but there is a lack of evidence to show which is the most suitable therapy. This study aimed to make concurrent multi-arm comparisons of the short-term and long-term outcomes of percutaneous ablation (PA), open (OLR) or laparoscopic liver resection (LLR) for these patients. This was a retrospective observational cohort study. A series of generalized propensity score methods for multiple treatment groups were performed to concurrently compare the clinical outcomes of these three treatment options to balance potential confounders. Regression standardization was used to account for hazard of all-cause mortality and recurrence of intergroup differences. Of the 1778 patients included, 1237, 307 and 234 underwent OLR, LLR and PA, respectively. After overlap weighting, which was the optimal adjustment strategy, patients in the minimally invasive group (LLR and PA groups) had few postoperative complications and short postoperative hospital stays (both P < 0.001). The 5-year recurrence-free survival (RFS) rate and 5-year overall survival (OS) rate were significantly higher in the LLR group when compared with the OLR and PA groups (RFS: 55.6% vs 48.0% vs 30.2%, P < 0.001; OS: 89.1% vs 79.7% vs 84.0%, P = 0.020). Multivariable Cox analysis and regression standardization showed that LLR was an independent factor for better RFS when compared with OLR and PA. In subgroup analysis, the long-term outcomes of patients with BCLC stage A HCC were consistent with the whole population. In the observational study using various covariate adjustment analysis with excellent balance, LLR is not only minimally invasive, but also provides better RFS and equivalent OS for patients with BCLC stage 0-A HCC when compared with OLR and PA.

COVARIATE-ADJUSTED ASSOCIATIONS OF COGNITION, DEPRESSIVE SYMPTOMS, AND SOCIAL SUPPORT WITH LIFE SPACE MOBILITY

Abstract Diabetes mellitus is one of the most common chronic diseases among older adults and can affect their movement, participation, and all aspects of daily living, thus restricting life space mobility. Life space mobility reflects individuals’ ability to move independently and engage in social activities. This study examines covariate-adjusted associations of cognition, depressive symptoms, amount of support received and satisfaction with support with life space mobility. The study included 247 older adults aged 65 and above from the University of Alabama at Birmingham (UAB) Diabetes and Aging Study of Health (DASH). Average age was 73, 45% of the sample were Black/African American, 53% were female, and 47% were married. Results from multiple covariate-adjusted regression analyses revealed that being Black/African American, older, female, and higher depressive symptoms significantly predicted lower life space mobility (all p’s &amp;lt; .05) while being married, educated, and reporting better health significantly predicted greater life space mobility. Similarly, higher cognitive function was a significant predictor of greater life space mobility (B = .140, p &amp;lt; .05). Results remained significant even when adjusted for covariates. Amount of support received and satisfaction with support did not predict life space mobility. Findings from this investigation identify individuals who are at risk for restricted life space mobility and suggest protective factors. Establishing these associations with life space mobility within a health disparities framework would be important as it would draw attention to functioning in later life for socially disadvantaged groups and help inform interventions.

Mediation analysis of the associations between neighbourhood walkability and greenness, accelerometer-measured physical activity, and health-related fitness in urban dwelling Canadians

ObjectiveTo estimate sex-specific associations (total, direct, and indirect effects) between objectively measured neighbourhood walkability and greenness and objectively measured physical activity and health-related fitness including cardiorespiratory and muscular fitness in Canadian adults. MethodsNeighbourhood walkability (Canadian Active Living Environment) and greenness (Normalized Difference Vegetation Index; NDVI) data were linked to cardiorespiratory (i.e., submaximal step test estimated V̇O2 max) and muscular fitness (i.e., handgrip strength) and accelerometer measured physical activity; Canadian Health Measures Survey). Covariate-adjusted sex-stratified path analyses was conducted to assess if physical activity (light: LPA; moderate: MPA, and; vigorous: VPA) mediated the associations between neighbourhood walkability, NDVI and health-related fitness. Model sample sizes ranged from 987 to 2796 for males and 989 to 2835 for females. ResultsAmong males, we found indirect effects between neighbourhood walkability and cardiorespiratory fitness via LPA (negative) and VPA (positive). We also found a total effect (negative) between neighbourhood walkability and grip strength and indirect effects between neighbourhood walkability and handgrip strength via LPA (negative) and MPA (negative). Among females, we found a total effect (positive) and direct effect (positive) between neighbourhood walkability and cardiorespiratory fitness, and an indirect effect for neighbourhood walkability and cardiorespiratory fitness via LPA. We found no significant effects related to neighbourhood greenness. ConclusionsResiding in a neighbourhood with higher walkability may positively affect cardiorespiratory fitness but negatively affect muscular strength. The negative associations between neighbourhood walkability and LPA may offset potential positive associations between neighbourhood walkability and MPA and VPA and their subsequent influence on health-related fitness.

MiTree: A Unified Web Cloud Analytic Platform for User-Friendly and Interpretable Microbiome Data Mining Using Tree-Based Methods.

The advent of next-generation sequencing has greatly accelerated the field of human microbiome studies. Currently, investigators are seeking, struggling and competing to find new ways to diagnose, treat and prevent human diseases through the human microbiome. Machine learning is a promising approach to help such an effort, especially due to the high complexity of microbiome data. However, many of the current machine learning algorithms are in a "black box", i.e., they are difficult to understand and interpret. In addition, clinicians, public health practitioners and biologists are not usually skilled at computer programming, and they do not always have high-end computing devices. Thus, in this study, we introduce a unified web cloud analytic platform, named MiTree, for user-friendly and interpretable microbiome data mining. MiTree employs tree-based learning methods, including decision tree, random forest and gradient boosting, that are well understood and suited to human microbiome studies. We also stress that MiTree can address both classification and regression problems through covariate-adjusted or unadjusted analysis. MiTree should serve as an easy-to-use and interpretable data mining tool for microbiome-based disease prediction modeling, and should provide new insights into microbiome-based diagnostics, treatment and prevention. MiTree is an open-source software that is available on our web server.

Social-environmental phenotypes of rapid cystic fibrosis lung disease progression in adolescents and young adults living in the United States

BackgroundCystic fibrosis (CF) is a genetic disease but is greatly impacted by non-genetic (social/environmental and stochastic) influences. Some people with CF experience rapid decline, a precipitous drop in lung function relative to patient- and/or center-level norms. Those who experience rapid decline in early adulthood, compared to adolescence, typically exhibit less severe clinical disease but greater loss of lung function. The extent to which timing and degree of rapid decline are informed by social and environmental determinants of health (geomarkers) is unknown. MethodsA longitudinal cohort study was performed (24,228 patients, aged 6–21 years) using the U.S. CF Foundation Patient Registry. Geomarkers at the ZIP Code Tabulation Area level measured air pollution/respiratory hazards, greenspace, crime, and socioeconomic deprivation. A composite score quantifying social-environmental adversity was created and used in covariate-adjusted functional principal component analysis, which was applied to cluster longitudinal lung function trajectories. ResultsSocial-environmental phenotyping yielded three primary phenotypes that corresponded to early, middle, and late timing of peak decline in lung function over age. Geographic differences were related to distinct cultural and socioeconomic regions. Extent of peak decline, estimated as forced expiratory volume in 1 s of % predicted/year, ranged from 2.8 to 4.1 % predicted/year depending on social-environmental adversity. Middle decliners with increased social-environmental adversity experienced rapid decline 14.2 months earlier than their counterparts with lower social-environmental adversity, while timing was similar within other phenotypes. Early and middle decliners experienced mortality peaks during early adolescence and adulthood, respectively. ConclusionWhile early decliners had the most severe CF lung disease, middle and late decliners lost more lung function. Higher social-environmental adversity associated with increased risk of rapid decline and mortality during young adulthood among middle decliners. This sub-phenotype may benefit from enhanced lung-function monitoring and personalized secondary environmental health interventions to mitigate chemical and non-chemical stressors.

Abstract 15693: Weekend Sleep Extension (Catch-up Sleep) is Associated With Lower Incidence of Coronary Calcium Score: The Elsa-Brasil Study

Background: Insufficient sleep is a worldwide public health problem with potential cardiovascular consequences. Therefore, strategies aiming at improving sleep patterns are highly desired. Cross-sectional studies showed that weekend sleep extension (catch-up sleep) is associated with better glucose metabolism and cognitive function profiles, but longitudinal studies are lacking. Hypothesis: Catch-up sleep may have protective effects on subclinical atherosclerosis. Methods: In this prospective cohort study, we performed a 7-days wrist actigraphy for monitoring sleep duration and a sleep study to detect sleep apnea. Catch-up-sleep was measured by calculating weekend sleep duration (Friday-Saturday nights) minus weekday sleep duration (Sunday-Thursday nights). Coronary artery calcium, CAC (64-slice multi-detector computed tomography) was measured at two different time points throughout the study (baseline, between 2010-2014, and follow-up, between 2016-2018). Incidence of subclinical atherosclerosis was defined as baseline CAC=0 followed by CAC&gt;0 at a 5-year follow-up visit. The association of incident CAC outcome was assessed using logistic regression adjusting for age, sex, race, body mass index, hypertension, diabetes mellitus, smoking, low- and high-density lipoprotein, use of statin, sleep apnea and interscan period). Analysis of incidence was Inverse probability censoring weighted. Results: We analyzed 1,832 participants with available CAC scores at baseline (age: 48.8±8.0years; 57.8% women; 32.1% with sleep apnea). The mean sleep duration was 6.6±1.0 hours. Catch-up-sleep &gt;90 minutes was observed in 28.0%. Incidence of CAC was 27/141 (19.1%) among subjects with catch-up-sleep &gt;90 minutes and 326/1029 (31.7%) among those with catch-up-sleep ≤90 minutes (P&lt;0.001). In covariate-adjusted analyses (n=1,170, follow-up=5.4±0.90 years), we found a lower incidence of CAC in those participants with weekend sleep extension &gt;90 minutes (OR=0.62; 95% CI 0.52-0.74). Conclusion: Catch-up sleep is independently associated with a lower incidence of CAC. These results underscore that catch-up sleep may mitigate the adverse cardiovascular effects of weekdays sleep restrictions frequently observed in our Society.

Effects of Opioid-Limiting Legislation in the State of Ohio on Opioid Prescriptions After Shoulder Arthroscopy.

Recent studies have shown that legislation regulating opioid prescriptions in the United States has been successful in reducing the morphine milligram equivalent (MME) prescribed after certain orthopaedic procedures. To (1) determine the effect of Ohio's legislation limiting opioid prescriptions after shoulder arthroscopy and (2) identify risk factors associated with prolonged opioid use and increased postoperative opioid dosing. Cohort study; Level of evidence, 3. We reviewed the data of patients who underwent shoulder arthroscopy between January 1, 2016, and March 31, 2020. Patients were classified according to the date of legislation passage (August 31, 2017) as before legislation (PRE) or on/after legislation (POST). Patients were also classified based on the number of opioid prescriptions filled within 30 days of surgery as opioid-tolerant (at least 1 prescription) or opioid-naïve (zero prescriptions). We recorded patient characteristics, medical comorbidities, and surgical details, as well as the number of opioid prescriptions, MME per prescription from 30 days preoperatively to 90 days postoperatively, and the number of gamma-aminobutyric acid (GABA) analogues and benzodiazepine prescriptions from 30 days preoperatively to the date of surgery. Differences between cohorts were compared with the Fisher exact test and Wilcoxon test. A covariate-adjusted regression analysis was used to evaluate risk factors associated with increased postoperative opioid dosing. Overall, 279 patients (n = 97 PRE; n = 182 POST; n = 42 opioid-tolerant; n = 237 opioid-naïve) were included in the final analysis. There was a significant reduction in the cumulative MME prescribed in the immediate (0-7 days) postoperative period (PRE, 450 MME vs POST, 315 MME), the first 30 postoperative days (PRE, 590 MME vs POST, 375 MME), and the first 90 postoperative days (PRE, 600 MME vs POST, 420 MME) (P < .001 for all). The opioid-tolerant cohort had higher MME at every time point in the postoperative period (P < .001). Consumption of preoperative opioid (β = 1682.5; P < .001), benzodiazepine (β = 468.09; P < .001), and GABA analogue (β = 251.37; P = .04) was associated with an increase in the cumulative MME prescribed. Opioid prescription-limiting legislation in Ohio significantly reduced the cumulative MME prescribed in the first 30 days postoperatively for both opioid-naïve and opioid-tolerant patients after shoulder arthroscopy. Consumption of opioids, benzodiazepines, and GABA analogues preoperatively was associated with increased postoperative opioid dosage.

Headache among combat-exposed veterans and service members and its relation to mild traumatic brain injury history and other factors: a LIMBIC-CENC study.

Headache (HA) is a common persistent complaint following mild traumatic brain injury (mTBI), but the association with remote mTBI is not well established, and risk factors are understudied. Determine the relationship of mTBI history and other factors with HA prevalence and impact among combat-exposed current and former service members (SMs). Secondary cross-sectional data analysis from the Long-Term Impact of Military-Relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium prospective longitudinal study. We examined the association of lifetime mTBI history, demographic, military, medical and psychosocial factors with (1) HA prevalence ("lately, have you experienced headaches?") using logistic regression and (2) HA burden via the Headache Impact Test-6 (HIT-6) using linear regression. Each lifetime mTBI was categorized by mechanism (blast-related or not) and setting (combat deployed or not). Participants with non-credible symptom reporting were excluded, leaving N = 1,685 of whom 81% had positive mTBI histories. At a median 10 years since last mTBI, mTBI positive participants had higher HA prevalence (69% overall, 78% if 3 or more mTBIs) and greater HA burden (67% substantial/severe impact) than non-TBI controls (46% prevalence, 54% substantial/severe impact). In covariate-adjusted analysis, HA prevalence was higher with greater number of blast-related mTBIs (OR 1.81; 95% CI 1.48, 2.23), non-blast mTBIs while deployed (OR 1.42; 95% CI 1.14, 1.79), or non-blast mTBIs when not deployed (OR 1.23; 95% CI 1.02, 1.49). HA impact was only higher with blast-related mTBIs. Female identity, younger age, PTSD symptoms, and subjective sleep quality showed effects in both prevalence and impact models, with the largest mean HIT-6 elevation for PTSD symptoms. Additionally, combat deployment duration and depression symptoms were factors for HA prevalence, and Black race and Hispanic/Latino ethnicity were factors for HA impact. In sensitivity analyses, time since last mTBI and early HA onset were both non-significant. The prevalence of HA symptoms among formerly combat-deployed veterans and SMs is higher with more lifetime mTBIs regardless of how remote. Blast-related mTBI raises the risk the most and is uniquely associated with elevated HA burden. Other demographic and potentially modifiable risk factors were identified that may inform clinical care.