Lifetime prevalence and correlates of colorectal cancer screening among low-income U.S. Veterans.

PURPOSE: The Veterans Health Administration (VHA) is the largest integrated healthcare system in the U.S. While preventive healthcare services are high priority in the VHA, low-income U.S. Veterans experience adverse life circumstances that may negatively impact their access to these services. This study examined lifetime prevalence as well as demographic, socioeconomic, military-specific, and clinical correlates of colorectal cancer (CRC) screening among low-income U.S. Veterans ≥ 50 years of age. METHODS: Cross-sectional data on 862 participants were analyzed from the 2021-2022 National Veteran Homeless and Other Poverty Experiences study. RESULTS: Overall, 55.3% (95% confidence interval [CI] 51.3-59.3%) reported ever-receiving CRC-screening services. In a multivariable logistic regression model, never-receivers of CRC screening were twice as likely to reside outside of the Northeast, and more likely to be married (odds ratio [OR] = 1.86, 95% CI 1.02, 3.37), have BMI < 25 kg/m2 [vs. 25- < 30 kg/m2] (OR = 1.75, 95% CI 1.19, 2.58), or ≥ 1 chronic condition (OR = 1.46, 95% CI 1.06, 2.02). Never-receivers of CRC screening were less likely to be female (OR = 0.53, 95% CI 0.29, 0.96), aged 65-79y [vs. ≥ 80y] (OR = 0.61, 95% CI 0.40, 0.92), live in 5 + member households (OR = 0.33, 95% CI 0.13, 0.86), disabled (OR = 0.45, 0.22, 0.92), with purchased health insurance (OR = 0.56, 95% CI 0.33, 0.98), or report alcohol-use disorder (OR = 0.10, 95% CI 0.02, 0.49) and/or HIV/AIDS (OR = 0.28, 95% CI 0.12, 0.68). CONCLUSION: Nearly 55% of low-income U.S. Veterans reported ever screening for CRC. Variations in CRC-screening behaviors according to veteran characteristics highlight potential disparities as well as opportunities for targeted behavioral interventions.

Growth Differentiation Factor 15 and Diet Quality Trajectory Interact to Determine Frailty Incidence among Middle-Aged Urban Adults.

BACKGROUND: Elevated plasma growth differentiation factor 15 (GDF15) and poor diet quality may be associated with increased frailty incidence, although their interactive associations have not been assessed in urban middle-aged adults. OBJECTIVES: We aimed to examine GDF15 and its interactive association with diet quality in relation to frailty incidence among a sample of middle-aged urban adults. METHODS: The relationship between GDF15 and diet quality trajectories in relation to incident frailty was examined in a longitudinal study of participants in the Healthy Aging in Neighborhoods of Diversity across the Life Span (2004-2017). Serum GDF15 concentration and frailty incidence were primary exposure and outcome, respectively. Group-based trajectory models were used to assess diet quality trajectories (≤3 visits/participant, N = 945, N' = 2247 observations) using the Healthy Eating Index 2010 version (HEI-2010), Dietary Inflammatory Index, and mean adequacy ratio (MAR). Cox proportional hazards models were used, testing interactive associations of GDF15 and diet quality trajectories with frail/prefrail incidence (N = 400 frailty-free at first visit, N' = 604 observations, n = 168 incident frail/prefrail). RESULTS: Both elevated GDF15 and lower diet quality trajectories were associated with a lower probability of remaining nonfrail (≤13 y follow-up). Among females, the "high diet quality" HEI-2010 trajectory had a hazard ratio (HR) of 0.15 [95% confidence interval (CI): 0.04, 0.54; P = 0.004; fully adjusted model] when compared with the "low diet quality" trajectory group. Among males only, there was an antagonistic interaction between lower HEI-2010 trajectory and elevated GDF15. Specifically, the HR for GDF15-frailty in the higher diet quality trajectory group (high/medium combined), and among males, was 2.69 (95% CI: 1.06, 6.62; P = 0.032), whereas among the lower diet quality trajectory group, the HR was 0.94 (95% CI: 0.49, 1.80; P = 0.86). Elevated GDF15 was independently associated with frailty among African American adults. CONCLUSIONS: Pending replication, we found an antagonistic interaction between GDF15 and HEI-2010 trajectory in relation to frailty incidence among males.

Plasma proteomic biomarkers and the association between poor cardiovascular health and incident dementia: The UK Biobank study.

BACKGROUND: The study examined how plasma proteome indicators may explain the link between poor cardiovascular health (CVH) and dementia risk. METHODS: The present study involved 28,974 UK Biobank participants aged 50-74y at baseline (2006-2010) who were followed-up for ≤ 15 y for incidence of dementia. CVH was calculated using Life's Essential 8 (LE8) total scores. The scores were standardized and reverse coded to reflect poor CVH (LE8z_rev). OLINK proteomics was available on this sample (k = 1,463 plasma proteins). The study primarily tested the mediating effects of the plasma proteome in LE8z_rev-dementia effect. The total effect was decomposed into "mediation only" or pure indirect effect (PIE), "interaction only" or interaction referent (INTREF), "neither mediation nor interaction" or controlled direct effect (CDE), and "both mediation and interaction" or mediated interaction (INTMED). RESULTS: The study found poorer CVH assessed by LE8z_rev increased the risk of all-cause dementia by 11 % [per 1 SD, hazard ratio, (HR) = 1.11, 95 % CI: 1.03-1.20, p = 0.005). The study identified 11 plasma proteins with strong mediating effects, with GDF15 having the strongest association with dementia risk (per 1 SD, HR = 1.24, 95 % CI: 1.16, 1.33, P < 0.001 when LE8z_rev is set at its mean value) and the largest proportion mediated combining PIE and INTMED (62.6 %; 48 % of TE is PIE), followed by adrenomedullin or ADM. A first principal component with 10 top mediators (TNFRSF1A, GDF15, FSTL3, COL6A3, PLAUR, ADM, GFRAL, ACVRL1, TNFRSF6B, TGFA) mediated 53.6 % of the LE8z_rev-dementia effect. Using all the significant PIE (k = 526) proteins, we used OLINK Insight pathway analysis to identify key pathways, which revealed the involvement of the immune system, signal transduction, metabolism, disease, protein metabolism, hemostasis, membrane trafficking, extracellular matrix organization, developmental biology, and gene expression among others. STRING analysis revealed that five top consistent proteomic mediators were represented in two larger clusters reflecting numerous interconnected biological gene ontology pathways, most notably cytokine-mediated signaling pathway for GDF15 cluster (GO:0019221) and regulation of peptidyl-tyrosine phosphorylation for the ADM cluster (GO:0050730). CONCLUSION: Dementia is linked to poor CVH mediated by GDF15 and ADM among several key proteomic markers which collectively explained âˆ¼ 54 % of the total effect.

Infection burden and its association with neurite orientation dispersion and density imaging markers in the UK Biobank.

BACKGROUND: Infection burden (IB), although linked to neurodegeneration, including Alzheimer's Disease (AD), has not been examined against neurite orientation, dispersion, and density imaging (NODDI) measures. METHODS: Among 38,803 UK Biobank adults (Age:40-70 years), we tested associations of total IB (IBtotal, 47.5 %) and hospital-treated IB (IBhosp, 9.7 %) with NODDI measures (5-15 years later), including volume fraction of Gaussian isotropic diffusion (ISOVF), intra-cellular volume fraction (ICVF) and orientation dispersion (OD) indices, using multiple linear regression models. RESULTS: Total and hospital-treated infection burdens (IBtotal and IBhosp) were associated with increased ISOVF, indicating increased free-water component. IBtotal was positively associated with OD, indicating that at higher IBtotal there was greater fanning of neurites. This was more evident in the lower cardiovascular health group. IBhosp was associated with higher OD, and lower ICVF at higher AD polygenic risk. Together, these findings indicate that both total and hospital-treated infections have effects on NODDI outcomes in the direction of poor brain health. These effects were largely homogeneous across cardiovascular health and AD polygenic risk groups, with some effects shown to be stronger at poor cardiovascular health and/or higher AD risk. CONCLUSIONS: Total and hospital-treated infections were associated with poorer white matter microstructure (higher ISOVF or OD or lower ICVF), with some heterogeneity across cardiovascular health and AD risk. Longitudinal studies with multiple repeats on neuroimaging markers in comparable samples are needed.

Serum neurofilament light chain as a prognostic marker of all-cause mortality in a national sample of US adults.

Neurofilament light chain (NfL) is a neuron-specific structural protein released into the extracellular space, including body fluids, upon neuroaxonal damage. Despite evidence of a link in neurological disorders, few studies have examined the association of serum NfL with mortality in population-based studies. Data from the National Health and Nutrition Survey were utilized including 2,071 Non-Hispanic White, Non-Hispanic Black and Hispanic adult participants and adult participants of other ethnic groups (20-85 years) with serum NfL measurements who were followed for ≤ 6 years till 2019. We tested the association of serum NfL with mortality in the overall population and stratified by sex with the addition of potential interactive and mediating effects of cardio-metabolic risk factors and nutritional biomarkers. Elevated serum NfL levels (above median group) were associated with mortality risk compared to the below median NfL group in the overall sample (P = 0.010), with trends observed within each sex group (P < 0.10). When examining Loge NfL as a continuum, one standard deviation of Loge NfL was associated with an increased mortality risk (HR = 1.88, 95% CI 1.60-2.20, P < 0.001) in the reduced model adjusted for age, sex, race, and poverty income ratio; a finding only slightly attenuated with the adjustment of lifestyle and health-related factors. Four-way decomposition indicated that there was, among others, mediated interaction between NfL and HbA1c and a pure inconsistent mediation with 25(OH)D3 in predicting all-cause mortality, in models adjusted for all other covariates. Furthermore, urinary albumin-to-creatinine ratio interacted synergistically with NfL in relation to mortality risk both on the additive and multiplicative scales. These data indicate that elevated serum NfL levels were associated with all-cause mortality in a nationally representative sample of US adults.

Opioid Use Disorder among Hospitalized Adults in North Carolina: Analysis from the 2000-2020 NC State Inpatient Database.

OBJECTIVES: Opioid use disorder (OUD) is characterized as a chronic condition that was first outlined in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and now the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision. It encompasses frequent opioid usage, cravings, the development of tolerance, withdrawal symptoms upon discontinuation, unsuccessful attempts to quit or reduce use, and recurrent use even when faced with negative consequences. Both national- and state-level data show that overdose deaths associated with prescription opioids are increasing at an alarming rate. The increasing overdose deaths from illicitly manufactured fentanyl and other synthetic opioids compound this epidemic's burden. The present study sought to determine the prevalence and potential factors associated with OUD in North Carolina. METHODS: Using the State Inpatient Database, a retrospective cross-sectional study was conducted to identify OUD-related discharges between 2000 and 2020. Descriptive statistics and rates of OUD per 1000 discharges were calculated. Simple and multivariable logistic regression models were used to identify factors associated with increased odds of having an opioid use disorder diagnosis at discharge. The deviance-Pearson goodness of fit statistic was also used. Variables were identified using International Classification of Diseases, Ninth Revision, Clinical Modification, and International Classification of Diseases, Tenth Revision, Clinical Modification, codes in the discharge records. RESULTS: Of 19,370,483 hospitalizations that occurred between 2000 and 2020 in North Carolina, 483,250 were associated with OUD, a prevalence rate of 24.9 cases per 1000 discharges. The highest OUD rates were seen among adults who self-paid for their hospitalization, those with Medicaid, and those with other types of payors such as Workers' Compensation and the Indian Health Service; individuals between 25 and 54 years old; tobacco and alcohol users; Native American patients; patients located in urban areas; patients with lower household income; White patients; and female patients. OUD also was associated with increased odds of having one or more comorbid psychiatric disorders when controlling for other factors. CONCLUSIONS: Although preventive measures are crucial, including policies that discourage prescribing opioids for noncancer pain and those that target the manufacturing and distribution of synthetic opioids, providing integrated care for patients with OUD and co-occurring psychiatric and/or physical disorders is equally important. These findings suggest the need for a system-wide public health response focused on the expansion of primary prevention and treatment efforts, including crisis services, harm reduction services, and recovery programs.

GDF15 and its association with cognitive performance over time in a longitudinal study of middle-aged urban adults.

Serum GDF15 levels are correlated with multiple neurodegenerative diseases. Few studies have tested this marker's association with middle-aged cognitive performance over time, and whether race affects this association is unknown. We examined associations of initial serum GDF15 concentrations with longitudinal cognitive performance, spanning domains of global mental status, visual and verbal memory, attention, fluency, and executive function in a sub-sample of adults participating in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study (n = 776, Agev1:30-66y, 45.6 % male, 57.0 % African American, 43.0 % below poverty). This analysis consisted of mixed-effects regression models applied to the total selected sample, while also stratifying the analyses by race in the main analyses and further stratifying by sex, age group and poverty status in an exploratory analysis. Our main findings, which passed multiple testing and covariate-adjustment, indicated that GDF15 was associated with poorer baseline performance on several cognitive tests, including animal fluency [overall sample: (Model 1: γ0 ± SE: -0.664 ± 0.208, P < 0.001; Model 2, γ0 ± SE: -0.498 ± 0.217, P < 0.05)]. Among White adults, GDF15 was linked to poorer performance on a brief test of attention (Model 1: γ0 ± SE: -0.426 ± 0.126, P < 0.001; Model 2, γ0 ± SE: -0.281 ± 0.139, P < 0.05); and Trailmaking test, part B (Model 1: γ0 ± SE: +0.129 ± 0.040, P < 0.001; Model 2, γ0 ± SE: +0.089 ± 0.041, P < 0.05), the latter being also linked to higher GDF15 among individuals living below poverty. Among women, GDF15 was associated with poor global mental status (Normalized MMSE: Model 1: γ0 ± SE: -2.617 ± 0.746, P < 0.001; Model 2: γ0 ± SE: -1.729 ± 0.709, P < 0.05). GDF15 was not associated with decline on any of the 11 cognitive test scores considered in âˆ¼ 4 years of follow-up. In sum, we detected cross-sectional associations between GDF15 and cognition, although GDF15 did not predict rate of change in cognitive performance over time among a sample of middle-aged adults. More longitudinal studies are needed to address the clinical utility of this biomarker for early cognitive defects.

Cardiovascular health, infection burden and their interactive association with brain volumetric and white matter integrity outcomes in the UK Biobank.

BACKGROUND: Cardiovascular health is associated with brain magnetic resonance imaging (MRI) markers of pathology and infections may modulate this association. METHODS: Using data from 38,803 adults (aged 40-70 years) and followed-up for 5-15 years, we tested associations of prevalent total (47.5%) and hospital-treated infection burden (9.7%) with brain structural and diffusion-weighted MRI (i.e., sMRI and dMRI, respectively) common in dementia phenome. Poor white matter tissue integrity was operationalized with lower global and tract-specific fractional anisotropy (FA) and higher mean diffusivity (MD). Volumetric sMRI outcomes included total, gray matter (GM), white matter (WM), frontal bilateral GM, white matter hyperintensity (WMH), and selected based on previous associations with dementia. Cardiovascular health was measured with Life's Essential 8 score (LE8) converted to tertiles. Multiple linear regression models were used, adjusting for intracranial volumes (ICV) for subcortical structures, and for demographic, socio-economic, and the Alzheimer's Disease polygenic risk score for all outcomes, among potential confounders. RESULTS: In fully adjusted models, hospital-treated infections were inversely related to GM (ß ± SE: -1042 ± 379, p = 0.006) and directly related to WMH as percent of ICV (Loge transformed) (ß ± SE:+0.026 ± 0.007, p < 0.001). Both total and hospital-treated infections were associated with poor WMI, while the latter was inversely related to FA within the lowest LE8 tertile (ß ± SE:-0.0011 ± 0.0003, p < 0.001, PLE8×IB < 0.05), a pattern detected for GM, Right Frontal GM, left accumbens and left hippocampus volumes. Within the uppermost LE8 tertile, total infection burden was linked to smaller right amygdala while being associated with larger left frontal GM and right putamen volumes, in the overall sample. Within that uppermost tertile of LE8, caudate volumes were also positively associated with hospital-treated infections. CONCLUSIONS: Hospital-treated infections had more consistent deleterious effects on volumetric and white matter integrity brain neuroimaging outcomes compared with total infectious burden, particularly in poorer cardiovascular health groups. Further studies are needed in comparable populations, including longitudinal studies with multiple repeats on neuroimaging markers.

Neuropsychological deficit profiles for service members with mild traumatic brain injury.

BACKGROUND: Neuropsychological deficits are generally assessed in terms of absolute level of functioning, e.g. high average, average, low average, although there is increased interest in calculating indices of relative degree of decline, e.g. mild, moderate, severe. OBJECTIVE: To examine differences in demographic, psychiatric, and military-specific characteristics for relative degree of decline in neuropsychological profiles attributed to traumatic brain injuries (TBIs) among service members (SMs). METHODS: Data were drawn from an existing clinical database of 269 SMs who received neuropsychological evaluations for TBI (Wechsler Test of Adult Reading, Wechsler Adult Intelligence Scale, California Verbal Learning Test, Delis-Kaplan Executive Function System) at a military treatment facility between 2013 and 2018. Independent sample t-tests and one-way ANOVA tests with pairwise comparisons were performed. RESULTS: Memory and problem-solving abilities were the most and least affected domains, respectively. Greater relative decline was observed among male and White SMs and those with post-traumatic stress disorder (PTSD). By contrast, there were no differences in relative decline according to military rank or work status. CONCLUSION: Relative degree of decline after TBI among SMs is differentially impacted according to neuropsychological domain, with greater impairment among male and White SMs as well as those with PTSD.

Pathways explaining racial/ethnic disparities in incident all-cause dementia among middle-aged US adults.

INTRODUCTION: Racial disparities in dementia incidence exist, but less is known about their presence and drivers among middle-aged adults. METHODS: We used time-to-event analysis among a sample of 4378 respondents (age 40-59 years at baseline) drawn from the third National Health and Nutrition Examination Surveys (NHANES III) with administrative linkage-spanning the years 1988-2014-to evaluate potential mediating pathways through socioeconomic status (SES), lifestyle, and health-related characteristics. RESULTS: Compared with Non-Hispanic White (NHW) adults, Non-White adults had a higher incidence of AD-specific (hazard ratio [HR] = 2.05, 95% confidence interval [CI]: 1.21, 3.49) and all-cause dementia (HR = 2.01, 95% CI: 1.36, 2.98). Diet, smoking, and physical activity were among characteristics on the pathway between race/ethnicity, SES, and dementia, with health-mediating effects of smoking and physical activity on dementia risk. DISCUSSION: We identified several pathways that may generate racial disparities in incident all-cause dementia among middle-aged adults. No direct effect of race was observed. More studies are needed to corroborate our findings in comparable populations.

Cardiovascular health, infection burden, and incident dementia in the UK Biobank.

INTRODUCTION: Among older adults, total and hospitalized infection may be associated with incidence of all-cause and Alzheimer's disease (AD) dementias, with variation by cardiovascular health (CVH). METHODS: We used Cox proportional hazards (PH) models to examine the relationships between International Classification of Diseases-10th revision (ICD-10)-specific viral and bacterial infectious agents and incident all-cause and AD dementia among 355,046 UK Biobank participants ≥50 years at baseline. Life's Essential 8 (LE8) index reflected CVH. RESULTS: In both sexes, total infection burden (yes vs. no) was associated with all-cause dementia, with significant interactions by LE8 tertiles, whereby this relationship was significant only in the lowest LE8 tertile. Hospital-treated infection burden (yes vs no) was significantly related to all-cause and AD dementia, with no significant interaction with LE8 tertile. Age group patterns were detected. DISCUSSION: AD and all-cause dementia were related to hospital-treated infections, while CVH modified the relationship of total infection burden with all-cause dementia. Highlights Secondary analysis on >355,000 UK Biobank participants ≥50 years at baseline. Alzheimer's disease and all-cause dementia are both related to hospital-treated infection. Cardiovascular health modifies association of infection burden with all-cause dementia.

Plasma neurofilament light and its association with all-cause mortality risk among urban middle-aged men and women.

BACKGROUND: Neurofilament light chain (NfL) is released into the blood during neuronal damage. NfL is linked to mortality in neurological disorders, remaining unexplored in population studies. We investigated whether initial (v1) and annualized change (δ) in plasma NfL can predict all-cause mortality in middle-aged dementia-free urban adults. METHODS: Longitudinal data were from 694 participants in the Healthy Aging in Neighborhoods of Diversity Across the Life Span study (HANDLS, mean agev1: 47.8 years, 42% male, 55.8% African American). Plasma NfL was measured prospectively at three visits. Analyses included Cox proportional hazards models for all-cause mortality risk and 4-way decomposition testing for interaction and mediation. RESULTS: Unlike men, women exhibited a direct association between δNfL (above vs. below median) and all-cause mortality risk in both the minimally (HR = 3.91, 95% CI 1.10-13.9, p = 0.036) and fully adjusted models (HR = 4.92, 95% CI 1.26-19.2, p = 0.022), and for δNfL (per unit increase) in the full model (HR = 1.65, 95% CI 1.04-2.61, p = 0.034). In both models, and among women, 1 standard deviation of NfLv1 was associated with an increased all-cause mortality risk (reduced model: HR = 2.01, 95% CI 1.24-3.25, p = 0.005; full model: HR = 1.75, 95% CI 1.02-2.98, p = 0.041). Only few interactions were detected for cardio-metabolic risk factors. Notably, NfLv1 was shown to be a better prognostic indicator at normal hsCRP values among women, while HbA1c and δNfL interacted synergistically to determine mortality risk, overall. CONCLUSIONS: These findings indicate that plasma NfL levels at baseline and over time can predict all-cause mortality in women and interacts with hsCRP and HbA1c to predict that risk.

BMI and Allostatic Load Are Directly Associated with Longitudinal Increase in Plasma Neurofilament Light among Urban Middle-Aged Adults.

BACKGROUND: Plasma neurofilament light chain (NfL) is a novel biomarker for age-related neurodegenerative disease. We tested whether NfL may be linked to cardiometabolic risk factors, including BMI, the allostatic load (AL) total score (ALtotal), and related AL continuous components (ALcomp). We also tested whether these relations may differ by sex or by race. METHODS: We used data from the HANDLS (Healthy Aging in Neighborhoods of Diversity across the Life Span) study [n = 608, age at visit 1 (v1: 2004-2009): 30-66 y, 42% male, 58% African American] to investigate associations of initial cardiometabolic risk factors and time-dependent plasma NfL concentrations over 3 visits (2004-2017; mean ± SD follow-up time: 7.72 ± 1.28 y), with outcomes being NfLv1 and annualized change in NfL (δNfL). We used mixed-effects linear regression and structural equations modeling (SM). RESULTS: BMI was associated with lower initial (γ01 = -0.014 ± 0.002, P < 0.001) but faster increase in plasma NfL over time (γ11 = +0.0012 ± 0.0003, P < 0.001), a pattern replicated for ALtotal. High-sensitivity C-reactive protein (hsCRP), serum total cholesterol, and resting heart rate at v1 were linked with faster plasma NfL increase over time, overall, while being uncorrelated with NfLv1 (e.g., hsCRP × Time, full model: γ11 = +0.004 ± 0.002, P = 0.015). In SM analyses, BMI's association with δNfL was significantly mediated through ALtotal among women [total effect (TE) = +0.0014 ± 0.00038, P < 0.001; indirect effect = +0.00042 ± 0.00019, P = 0.025; mediation proportion = 30%], with only a direct effect (DE) detected among African American adults (TE = +0.0011 ± 0.0004, P = 0.015; DE = +0.0010 ± 0.00048, P = 0.034). The positive associations between ALtotal/BMI and δNfL were mediated through increased glycated hemoglobin (HbA1c) concentrations, overall. CONCLUSIONS: Cardiometabolic risk factors, particularly elevated HbA1c, should be screened and targeted for neurodegenerative disease, pending comparable longitudinal studies. Other studies examining the clinical utility of plasma NfL as a neurodegeneration marker should account for confounding effects of BMI and AL.

Helicobacter pylori, periodontal pathogens, and their interactive association with incident all-cause and Alzheimer's disease dementia in a large national survey.

Co-infection between Helicobacter pylori (Hp) and groups of periodontal pathogens may alter the onset of Alzheimer's disease (AD) and all-cause dementia. We examined the interactive associations among Hp sero-positivity, periodontal disease (Pd), and infections with incident AD and all-cause dementia, among older adults (≥65 years at baseline). Up to 1431 participants from phase 1 of the National Health and Nutrition Survey III (1988-1991) had complete data till January 1st, 2014 on Hp sero-positivity with a mean follow-up of 10-11 years for AD and all-cause dementia incidence. Exposures consisted of 19 periodontal pathogens, constructed factors and clusters, and two Pd markers- probing depth and clinical attachment loss (CAL). Cox proportional hazards models were performed. Around 55% of the selected sample was Hp+. We found that Prevotella intermedia, Campylobacter Rectus, Factor 2 (Pi/Prevotella nigrescens/Prevotella melaninogenica), and the Orange-Red cluster interacted synergistically with Hp sero-positivity, particularly with respect to AD incidence. The presence of higher levels of Actinomyces Naeslundii (An) enhanced the effect of being Hp+ on both AD and all-cause dementia incidence. In contrast, Fusobacterim nucleatum (Fn), and Factor 1 (which included Fn), exhibited an antagonistic interaction with Hp in relation to all-cause dementia. Both probing depth and CAL had direct associations with all-cause dementia among Hp+ individuals, despite nonsignificant interaction. Selected periodontal pathogen titers, factors, and clusters interacted mostly synergistically, with Hp sero-positivity, to alter the risk of AD and all-cause dementia. Ultimately, a randomized controlled trial is needed, examining effects of co-eradication of Hp and select periodontal pathogens on neurodegenerative disease.

Substance Use Disorder among Hospitalized Adolescents in North Carolina.

OBJECTIVES: Individuals who began using alcohol or other drugs before the age of 15 are 7 times more likely to develop a substance use disorder (SUD) in adulthood. This study sought to determine the common characteristics of SUD-related hospitalizations and patterns of discharge diagnoses among adolescents in North Carolina. METHODS: Using the 2014 State Inpatient Database (SID), discharge records associated with the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnostic codes for SUD were identified. Adolescents between the ages of 13 and 19 years were included. SUD and non-SUD groups were compared using the Student t test for continuous variables and the χ2 test for categorical variables. A total of 1.1 million hospital discharges were analyzed. A uniform and standardized coding system called Clinical Classifications Software was used to identify cases. The Clinical Classifications Software collapses the ICD-9-CM codes into 679 clinically meaningful categories. A cluster of 3900 ICD-9-CM procedure codes also was used to identify clinically relevant groups of procedures performed during hospitalization. RESULTS: An estimated 3276 adolescents associated with SUD were discharged from North Carolina hospitals during the study year. Discharged patients with a SUD spent a total of 21,242 inpatient days, at a cost of $62 million. Among the adolescents with a SUD, 53% were boys, 62% were White, 24% were Black, 8% were Hispanic (8%), and 6% were of other races. Compared with patients without a SUD, those with a SUD had longer mean hospital stays (6.5 days vs 4.7 days; P < 0.0001) and lower mean hospital charge per hospitalization ($18,932 vs 24,532; P < 0.0001). Adolescents with a SUD also were diagnosed primarily as having mood disorders (44.78%), followed by schizophrenia and other psychological disorders, upon discharge. Approximately 37% of the SUD-related discharges occurred in areas, denoted in this study using ZIP code designations, with mean household annual incomes <$38,999. A large proportion of the SUD-related hospitalizations (44%) were billed to Medicaid. Frequently observed diagnoses associated with adolescents with a SUD were mood disorders (45%), schizophrenia (7%), and poisoning by other medications and drugs (4%). In 16% of hospitalized adolescents with a SUD, there were at least 2 procedures performed. There was a statistically significant mean hospital charge difference of $5600 between SUD and non-SUD teens. CONCLUSIONS: The literature reflects the connection between adolescent use and the propensity for diagnosis with a SUD in adulthood; it is evident that this is a growing public health crisis. This study identified patterns of adolescent substance use that, based on the current literature, are indicative of problematic futures for these individuals. The concerning data and literature identify a significant need to address prevention, treatment, and recovery services for adolescents, not only in North Carolina but throughout the United States. The need for focused interventions, access to care, and funding of substance-specific adolescent education and services is greatly needed to change the trajectory of these adolescents' lives.

The impact of obesity in patients hospitalized with opioid/opiate overdose.

Background: Although a direct link between opioid use in obese patients and risk of overdose has not been established, obesity is highly associated with higher risk for opioid/opiate overdose. Evidence for clinical impact of obesity on patients with opioid/opiate overdose is scarce. The aim of this study was to determine effects of obesity on health-care outcomes and mortality trends in hospitalized patients who presented with opioid/opiate overdose in the United States between 2010 and 2014. Design: Multivariate logistic and linear regression analysis compared clinical outcomes and hospital resource utilization between obese and nonobese patients. Trend analysis of in-hospital mortality was also analyzed. Setting: United States. Participants: 302,863 adults ≥ 18 years and hospitalized with a principle diagnosis of opioid/opiate overdoses between 2010 and 2014. Measurements: Primary measurement was in-hospital mortality. Secondary measurements included respiratory failure, cardiogenic shock, mechanical ventilations/intubations, hospital charges, and length of stay. Findings: Prevalence for in-hospital mortality was lower in patients with obesity (2.2% vs 2.9%). Obese patients had higher adjusted odds for respiratory failure (aOR = 1.7, [(CI) 1.6-1.8]) and mechanical ventilation/intubation (aOR = 1.17, [(CI) 1.10-1.2]). They also had longer length of stays (aMD = 0.4 days, [(CI) 0.25-0.58 days] and higher total hospital charges (aMD = $5,561, [(CI) $3,638-$7,483]. Trends of in-hospital mortality for patients with obesity did not significantly increase (2.1% in 2010 to 2.4% in 2014, p trend = 0.37), but significantly increased for obese patients (2.4% in 2010 to 3.4% in 2014; p trend <0.01). Conclusions: Prevalence and trends of mortality were lower in patients with obesity hospitalized for opiate/opioid overdose compared to those without obesity between 2010 and 2014 in the United States.

Sex Differences in Patterns of Sleep Disorders Among Hospitalizations With Parkinson's Disease: 2004-2014 Nationwide Inpatient Sample.

OBJECTIVE: This study aimed to examine patterns of sleep disorders among hospitalized adults 65 years and older as related to Parkinson's disease (PD) status and to evaluate sex differences in the associations between PD with sleep disorders. METHODS: A cross-sectional study was conducted using 19,075,169 hospital discharge records (8,169,503 men and 10,905,666 women) from the 2004-2014 Nationwide Inpatient Sample databases. PD and sleep disorder diagnoses were identified based on International Classification of Diseases, Ninth Revision, Clinical Modification coding. Logistic regression models were constructed for each sleep disorder as a correlate of PD status; adjusted odds ratios (aOR) with their 95% confidence intervals (CIs) were calculated taking into account patient and hospital characteristics. RESULTS: Period prevalences of PD and sleep disorder were estimated to be 2.1% and 8.1%, respectively. Most sleep disorder types, with the exception of sleep-related breathing disorders, were positively associated with PD diagnosis. Statistically significant interactions by sex were noted for associations of insomnia (men: aOR = 1.29, 95% CI = 1.24-1.36; women: aOR = 1.17, 95% CI = 1.12-1.22), parasomnia (men: aOR = 3.74, 95% CI = 3.44-4.07; women: aOR = 2.69, 95% CI = 2.44-2.96), sleep-related movement disorder (men: aOR = 1.09, 95% CI = 1.07-1.11; women: aOR = 1.22, 95% CI = 1.20-1.25), and any sleep disorder (men: aOR = 1.06, 95% CI = 1.05-1.08; women: aOR = 1.15, 95% CI = 1.13-1.17) with PD status. CONCLUSIONS: Overall, hospitalized men are more likely to experience PD with insomnia or parasomnia, whereas hospitalized women are more likely to experience PD with sleep-related movement disorder or any sleep disorder. Prospective cohort studies are needed to replicate these cross-sectional findings.

Systemic inflammation is associated with depressive symptoms differentially by sex and race: a longitudinal study of urban adults.

Systemic inflammation may influence trajectories of depressive symptoms over time, perhaps differentially by sex and race. Inflammatory markers and the Center for Epidemiologic Studies-Depression scale [total score: CES-Dtotal and four distinctive domains: somatic complaints, depressed affect, positive affect and interpersonal problems] were examined among African-American (AA) and White urban adults participating in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study [2004-2013, Agebase:30-64 y, mean ± SD follow-up time: 4.64 ± 0.93 y, N = 150 (with cytokine data) to N = 1,767 (with other inflammatory markers)]. Findings suggest that serum concentrations of high-sensitivity C-reactive protein (hsCRP), z-inflammation composite score [ICS, combining elevated hsCRP and ESR with low serum albumin and iron], and serum interleukin (IL) 1ß were positively associated with ΔCES-Dtotal (Δ: annual rate of increase) among Whites only. IL-12 was directly related to ΔCES-Dtotal among men and AA. The race-specific associations of hsCRP, ICS, IL-1ß and the sex-specific association of IL-12 with ΔCES-Dtotal were replicated for the "depressed affect" domain. Similarly, among men, lower serum albumin and higher ICS were linked with higher baseline "somatic complaints". IL-10 among AA and IL-12 among men were inversely related to Δ"positive affect", while "interpersonal problems" were cross-sectionally associated with IL-6 among AA and IL-10 among Whites. Finally, baseline ICS was positively associated with incident "elevated depressive symptoms" (EDS: CES-Dtotal ≥ 16) among AA (HR = 1.28, 95% CI: 1.04-1.56, P = 0.017). Overall, systemic inflammation was directly linked to increased depressive symptoms over time and at baseline, differentially across sex and race groups. More longitudinal research is needed to replicate our findings.

Regional variation in outcomes and healthcare resources utilization in, emergency department visits for syncope.

BACKGROUND: Management of patients with syncope lacks standardization. We sought to assess regional variation in hospitalization rates and resource utilization of patients with syncope. METHODS: We identified adults with syncope using the Nationwide Emergency Department Sample from years 2006 to 2014. Demographics and comorbidity characteristics were compared across geographic regions in the US. Multiple regression was conducted to compare outcomes. RESULTS: 9,132,176 adults presented with syncope. Syncope in the Northeast (n = 1,831,889) accounted for 20.1% of visits; 22.6% in the Midwest (n = 2,060,940), 38.5% in the South (n = 3,527,814) and 18.7% in the West (n = 1,711,533). Mean age was 56 years with 57.7% being female. The Northeast had the highest risk-adjusted hospitalization rate (24.5%) followed by the South (18.6%, ORadj 0.58; 95% CI 0.52-0.65, p < 0.001), the Midwest (17.2%, ORadj 0.51; 95% CI 0.46-0.58, p < 0.001) and West (15.8%, ORadj 0.45; 95% CI 0.39-0.51, p < 0.001). Risk-adjusted rates of syncope hospitalizations significantly declined from 25.8% (95% CI 24.8%-26.7%) in 2006 to 11.7% (95% CI 11.0%-12.5%) in 2014 (Ptrend < 0.001). The Northeast had the lowest risk-adjusted ED (Emergency Department) service charges per visit ($3320) followed by the Midwest ($4675, IRRadj 1.41; 95% CI 1.30-1.52, p < 0.001), the West ($4814, IRRadj 1.45; 95% CI 1.31-1.60, p < 0.001) and South ($4969, IRRadj 1.50; 95% CI 1.38-1.62, p < 0.001). Service charges increased from $3047/visit (95% CI $2912-$3182) in 2006 to $6267/visit (95% CI $5947-$6586) in 2014 (Ptrend < 0.001). CONCLUSIONS: Significant regional variability in hospitalization rates and ED service charges exist among patients with syncope. Standardizing practices may be needed to reduce variability.

Radiographic clues to the unstable knee: are findings of trochlear dysplasia on lateral knee radiographs reliable and predictive of patellar dislocation?

BACKGROUND: Trochlear dysplasia (TD) is a key predisposing risk factor for patellar instability (PI) and lateral patellar dislocation (LPD) injuries. It is useful to understand the reliability of radiographic findings of TD and the accuracy of knee radiographs in diagnosing patients with recent LPD. PURPOSE: The purposes of our study are to evaluate the inter-rater reliability of specific radiographic signs of PI and staging of TD between radiologists and orthopedic surgeons, and to identify which findings are associated with recent LPD. METHODS: This retrospective study comprised 336 patients aged 8 to 18 who obtained knee radiographs over a 3-year period. Two radiologists and two orthopedic surgeons, blinded to patient history, examined radiographs for indicators of PI. Using data from 19 confirmed LPD cases and 317 controls, inter-observer agreement (kappa, Pearson's correlation coefficient) was assessed, as was the odds ratio for likelihood of LPD. RESULTS: There was nearly perfect agreement between radiologists for patella-tendon ratios (Pearson's correlation coefficient 0.8377, P < 0.0001) and discrimination between normal knees and high-grade TD (kappa 0.9213, P < 0.0001). There is fair agreement between radiologists and surgeons distinguishing between normal knees and high-grade TD (kappa 0.5843, P < 0.0001). Lateral knee radiographs interpreted as high-grade TD were highly predictive of LPD (odds ratio 7.58-54.8) among all readers. CONCLUSIONS: There is high agreement between radiologists when evaluating lateral knee radiographs for signs of TD, validating the results of prior literature. Radiographic findings TD, patella alta, and effusion are variable predictors of recent LPD, greatest among patients with TD.