The Incidence and Cumulative Risk of Major Surgery in Older Persons in the United States.

OBJECTIVE: The objective of this study was to estimate the incidence and cumulative risk of major surgery in older persons over a 5-year period and evaluate how these estimates differ according to key demographic and geriatric characteristics. BACKGROUND: As the population of the United States ages, there is considerable interest in ensuring safe, high-quality surgical care for older persons. Yet, valid, generalizable data on the occurrence of major surgery in the geriatric population are sparse. METHODS: We evaluated data from a prospective longitudinal study of 5571 community-living fee-for-service Medicare beneficiaries, aged 65 or older, from the National Health and Aging Trends Study from 2011 to 2016. Major surgeries were identified through linkages with Centers for Medicare and Medicaid Services data. Population-based incidence and cumulative risk estimates incorporated National Health and Aging Trends Study analytic sampling weights and cluster and strata variables. RESULTS: The nationally representative incidence of major surgery per 100 person-years was 8.8, with estimates of 5.2 and 3.7 for elective and nonelec-tive surgeries. The adjusted incidence of major surgery peaked at 10.8 in persons 75 to 79 years, increased from 6.6 in the non-frail group to 10.3 in the frail group, and was similar by sex and dementia. The 5-year cumulative risk of major surgery was 13.8%, representing nearly 5 million unique older persons, including 12.1% in persons 85 to 89 years, 9.1% in those ≥90 years, 12.1% in those with frailty, and 12.4% in those with probable dementia. CONCLUSIONS: Major surgery is a common event in the lives of community-living older persons, including high-risk vulnerable subgroups.

The Contribution of Chronic Conditions to Hospitalization, Skilled Nursing Facility Admission, and Death: Variation by Race.

Multimorbidity (≥2 chronic conditions) is a common and important marker of aging. To better understand racial differences in multimorbidity burden and associations with important health-related outcomes, we assessed differences in the contribution of chronic conditions to hospitalization, skilled nursing facility admission, and mortality among non-Hispanic Black and non-Hispanic White older adults in the United States. We used data from a nationally representative study, the National Health and Aging Trends Study, linked to Medicare claims from 2011-2015 (n = 4,871 respondents). This analysis improved upon prior research by identifying the absolute contributions of chronic conditions using a longitudinal extension of the average attributable fraction for Black and White Medicare beneficiaries. We found that cardiovascular conditions were the greatest contributors to outcomes among White respondents, while the greatest contributor to outcomes for Black respondents was renal morbidity. This study provides important insights into racial differences in the contributions of chronic conditions to costly health-care utilization and mortality, and it prompts policy-makers to champion delivery reforms that will expand access to preventive and ongoing care for diverse Medicare beneficiaries.

Risk Factors of Skilled Nursing Facility Admissions and the Interrelation With Hospitalization and Amount of Informal Caregiving Received.

BACKGROUND: The correlations between skilled nursing facility (SNF) admissions, number of hospitalizations, and informal caregiving hours received after adjusting for physical and cognitive function and sociodemographic covariates are not well understood. OBJECTIVE: The objective of this study was to better understand risk factors for SNF admissions and the interrelation with hospitalizations and amount of informal caregiving received, this study applied a novel joint modeling analysis to simultaneously explore the correlation and shared information between the 3 outcomes. RESEARCH DESIGN: This was an observational follow-up study. SUBJECTS: Data from 4836 older Americans included in the 2011-2015 rounds of the National Health and Aging Trends Study were linked with Centers for Medicare & Medicaid Services. MEASURES: We jointly modeled SNF admission, hospital admissions, and informal caregiving hours received while accounting for possible risk factors. We addressed missing values by multiple imputation with chained equations. RESULTS: SNF admission evidenced a strong positive correlation with hospital admission, and SNF admission evidenced a weak positive correlation with the informal caregiving hours received after adjustment for important risk factors. Non-Hispanic White race/ethnicity, living alone, not being Medicaid eligible, Alzheimer disease and related dementias diagnosis, activities of daily living disabilities, and frailty were associated with increased risk of SNF admissions and any/number of hospital admission. Lower educational level was also associated with the latter. Medicaid eligibility was the only factor not associated with any nor numbers of informal caregiving hours received. CONCLUSIONS: Sociodemographic and health factors were important for predicting SNF admissions. After adjustment for important risk factors, SNF evidenced a strong positive correlation with the number of hospitalizations and a weak positive correlation with the hours of informal caregiving received.

Review and evaluation of imputation methods for multivariate longitudinal data with mixed-type incomplete variables.

Estimating relationships between multiple incomplete patient measurements requires methods to cope with missing values. Multiple imputation is one approach to address missing data by filling in plausible values for those that are missing. Multiple imputation procedures can be classified into two broad types: joint modeling (JM) and fully conditional specification (FCS). JM fits a multivariate distribution for the entire set of variables, but it may be complex to define and implement. FCS imputes missing data variable-by-variable from a set of conditional distributions. In many studies, FCS is easier to define and implement than JM, but it may be based on incompatible conditional models. Imputation methods based on multilevel modeling show improved operating characteristics when imputing longitudinal data, but they can be computationally intensive, especially when imputing multiple variables simultaneously. We review current MI methods for incomplete longitudinal data and their implementation on widely accessible software. Using simulated data from the National Health and Aging Trends Study, we compare their performance for monotone and intermittent missing data patterns. Our simulations demonstrate that in a longitudinal study with a limited number of repeated observations and time-varying variables, FCS-Standard is a computationally efficient imputation method that is accurate and precise for univariate single-level and multilevel regression models. When the analyses comprise multivariate multilevel models, FCS-LMM-latent is a statistically valid procedure with overall more accurate estimates, but it requires more intensive computations. Imputation methods based on generalized linear multilevel models can lead to biased subject-level variance estimates when the statistical analyses involve hierarchical models.

Synaptic density and cognitive performance in Alzheimer's disease: A PET imaging study with [11 C]UCB-J.

INTRODUCTION: For 30 years synapse loss has been referred to as the major pathological correlate of cognitive impairment in Alzheimer's disease (AD). However, this statement is based on remarkably few patients studied by autopsy or biopsy. With the recent advent of synaptic vesicle glycoprotein 2A (SV2A) positron emission tomography (PET) imaging, we have begun to evaluate the consequences of synaptic alterations in vivo. METHODS: We examined the relationship between synaptic density measured by [11 C]UCB-J PET and neuropsychological test performance in 45 participants with early AD. RESULTS: Global synaptic density showed a significant positive association with global cognition and performance on five individual cognitive domains in participants with early AD. Synaptic density was a stronger predictor of cognitive performance than gray matter volume. CONCLUSION: These results confirm neuropathologic studies demonstrating a significant association between synaptic density and cognitive performance, and suggest that this correlation extends to the early stages of AD.

Oxytocin enhances brain function in children with autism.

Following intranasal administration of oxytocin (OT), we measured, via functional MRI, changes in brain activity during judgments of socially (Eyes) and nonsocially (Vehicles) meaningful pictures in 17 children with high-functioning autism spectrum disorder (ASD). OT increased activity in the striatum, the middle frontal gyrus, the medial prefrontal cortex, the right orbitofrontal cortex, and the left superior temporal sulcus. In the striatum, nucleus accumbens, left posterior superior temporal sulcus, and left premotor cortex, OT increased activity during social judgments and decreased activity during nonsocial judgments. Changes in salivary OT concentrations from baseline to 30 min postadministration were positively associated with increased activity in the right amygdala and orbitofrontal cortex during social vs. nonsocial judgments. OT may thus selectively have an impact on salience and hedonic evaluations of socially meaningful stimuli in children with ASD, and thereby facilitate social attunement. These findings further the development of a neurophysiological systems-level understanding of mechanisms by which OT may enhance social functioning in children with ASD.

National Estimates of Short- and Longer-Term Hospital Readmissions After Major Surgery Among Community-Living Older Adults.

Importance: Nationally representative estimates of hospital readmissions within 30 and 180 days after major surgery, including both fee-for-service and Medicare Advantage beneficiaries, are lacking. Objectives: To provide population-based estimates of hospital readmission within 30 and 180 days after major surgery in community-living older US residents and examine whether these estimates differ according to key demographic, surgical, and geriatric characteristics. Design, Setting, and Participants: A prospective longitudinal cohort study of National Health and Aging Trends Study data (calendar years 2011-2018), linked to records from the Centers for Medicare & Medicaid Services (CMS). Data analysis was conducted from April to August 2023. Participants included community-living US residents of the contiguous US aged 65 years or older who had at least 1 major surgery from 2011 to 2018. Data analysis was conducted from April 10 to August 28, 2023. Main Outcomes and Measures: Major operations and hospital readmissions within 30 and 180 days were identified through data linkages with CMS files that included both fee-for-service and Medicare Advantage beneficiaries. Data on frailty and dementia were obtained from the annual National Health and Aging Trends Study assessments. Results: A total of 1780 major operations (representing 9 556 171 survey-weighted operations nationally) were identified from 1477 community-living participants; mean (SD) age was 79.5 (7.0) years, with 56% being female. The weighted rates of hospital readmission were 11.6% (95% CI, 9.8%-13.6%) for 30 days and 27.6% (95% CI, 24.7%-30.7%) for 180 days. The highest readmission rates within 180 days were observed among participants aged 90 years or older (36.8%; 95% CI, 28.3%-46.3%), those undergoing vascular surgery (45.8%; 95% CI, 37.7%-54.1%), and persons with frailty (36.9%; 95% CI, 30.8%-43.5%) or probable dementia (39.0%; 95% CI, 30.7%-48.1%). In age- and sex-adjusted models with death as a competing risk, the hazard ratios for hospital readmission within 180 days were 2.29 (95% CI, 1.70-3.09) for frailty and 1.58 (95% CI, 1.15-2.18) for probable dementia. Conclusions and Relevance: In this nationally representative cohort study of community-living older US residents, the likelihood of hospital readmissions within 180 days after major surgery was increased among older persons who were frail or had probable dementia, highlighting the potential value of these geriatric conditions in identifying those at increased risk.

Prior Influenza Infection Mitigates SARS-CoV-2 Disease in Syrian Hamsters.

Seasonal infection rates of individual viruses are influenced by synergistic or inhibitory interactions between coincident viruses. Endemic patterns of SARS-CoV-2 and influenza infection overlap seasonally in the Northern hemisphere and may be similarly influenced. We explored the immunopathologic basis of SARS-CoV-2 and influenza A (H1N1pdm09) interactions in Syrian hamsters. H1N1 given 48 h prior to SARS-CoV-2 profoundly mitigated weight loss and lung pathology compared to SARS-CoV-2 infection alone. This was accompanied by the normalization of granulocyte dynamics and accelerated antigen-presenting populations in bronchoalveolar lavage and blood. Using nasal transcriptomics, we identified a rapid upregulation of innate and antiviral pathways induced by H1N1 by the time of SARS-CoV-2 inoculation in 48 h dual-infected animals. The animals that were infected with both viruses also showed a notable and temporary downregulation of mitochondrial and viral replication pathways. Quantitative RT-PCR confirmed a decrease in the SARS-CoV-2 viral load and lower cytokine levels in the lungs of animals infected with both viruses throughout the course of the disease. Our data confirm that H1N1 infection induces rapid and transient gene expression that is associated with the mitigation of SARS-CoV-2 pulmonary disease. These protective responses are likely to begin in the upper respiratory tract shortly after infection. On a population level, interaction between these two viruses may influence their relative seasonal infection rates.

Neural processing of intentional biological motion in unaffected siblings of children with autism spectrum disorder: an fMRI study.

Despite often showing behaviorally typical levels of social cognitive ability, unaffected siblings of children with autism spectrum disorder have been found to show similar functional and morphological deficits within brain regions associated with social processing. They have also been reported to show increased activation to biological motion in these same regions, such as the posterior superior temporal sulcus (pSTS), relative to both children with autism and control children. It has been suggested that this increased activation may represent a compensatory reorganization of these regions as a result of the highly heritable genetic influence of autism. However, the response patterns of unaffected siblings in the domain of action perception are unstudied, and the phenomenon of compensatory activation has not yet been replicated. The present study used functional magnetic resonance imaging to determine the neural responses to intentional biological actions in 22 siblings of children with autism and 22 matched controls. The presented actions were either congruent or incongruent with the actor's emotional cue. Prior studies reported that typically developing children and adults, but not children with autism, show increased activation to incongruent actions (relative to congruent), within the pSTS and dorsolateral prefrontal cortex. We report that unaffected siblings did not show a compensatory response, or a preference for incongruent over congruent trials, in any brain region. Moreover, interaction analyses revealed a sub-region of the pSTS in which control children showed an incongruency preference to a significantly greater degree than siblings, which suggests a localized deficit in siblings. A sample of children with autism also did not show differential activation in the pSTS, providing further evidence that it is an area of selective disruption in children with autism and siblings. While reduced activation to both conditions was unique to the autism sample, lack of differentiation to incongruent and congruent intentional actions was common to both children with ASD and unaffected siblings.

Neural signatures of autism.

Functional magnetic resonance imaging of brain responses to biological motion in children with autism spectrum disorder (ASD), unaffected siblings (US) of children with ASD, and typically developing (TD) children has revealed three types of neural signatures: (i) state activity, related to the state of having ASD that characterizes the nature of disruption in brain circuitry; (ii) trait activity, reflecting shared areas of dysfunction in US and children with ASD, thereby providing a promising neuroendophenotype to facilitate efforts to bridge genomic complexity and disorder heterogeneity; and (iii) compensatory activity, unique to US, suggesting a neural system-level mechanism by which US might compensate for an increased genetic risk for developing ASD. The distinct brain responses to biological motion exhibited by TD children and US are striking given the identical behavioral profile of these two groups. These findings offer far-reaching implications for our understanding of the neural systems underlying autism.

Associations between dementia staging, neuropsychiatric behavioral symptoms, and divorce or separation in late life: A case control study.

Dementia can be difficult for married couples for many reasons, including the introduction of caregiving burden, loss of intimacy, and financial strain. In this study, we investigated the impact of dementia staging and neuropsychiatric behavioral symptoms on the likelihood of divorce or separation for older adult married couples. For this case-control study, we used data from the National Alzheimer's Coordinating Center (NACC) Uniform dataset (UDS) versions 2 and 3. This dataset was from 2007 to 2021 and contains standardized clinical information submitted by NIA/NIH Alzheimer's Disease Research Centers (ADRCs) across the United States (US). This data was from 37 ADRCs. We selected participants who were married or living as married/domestic partners at their initial visit. Cases were defined by a first divorce/separation occurring during the follow-up period, resulting in 291 participants. We selected 5 controls for each married/living as married case and matched on age. Conditional logistic regression estimated the association between overall Neuro Psychiatric Inventory (NPI) score and severity of individual symptoms of the NPI with case/control status, adjusted for education, the CDR® Dementia Staging Instrument score, living situation, symptom informant, sex, and race. Separate analyses were conducted for each symptom. Multiple comparisons were accounted for with the Hochberg method. Later stage of dementia was negatively associated with divorce/separation with an adjusted odds ratio (AOR) = 0.68 (95%CI = 0.50 to 0.93). A higher overall NPI score was positively associated with divorce/separation AOR = 1.08 (95% CI = 1.03 to 1.12,). More severe ratings of agitation/aggression, depression/dysphoria, disinhibition, and elation/euphoria were associated with greater odds of divorce/separation. Among older adults in the US, a later stage of dementia is associated with a lower likelihood of divorce or separation, while having more severe neuropsychiatric behavioral symptoms of agitation/aggression, depression/dysphoria, disinhibition, and elation/euphoria are associated with a higher likelihood of divorce or separation.

A Joint Model for Disability, Self-Rated Health, and Mortality Among Medicare Beneficiaries-Differences by Chronic Disease and Race/Ethnicity.

OBJECTIVES: Quantifying interdependence in multiple patient-centered outcomes is important for understanding health declines among older adults. METHODS: Medicare-linked National Health and Aging Trends Study data (2011-2015) were used to estimate a joint longitudinal logistic regression model of disability in activities of daily living (ADL), fair/poor self-rated health (SRH), and mortality. We calculated personalized concurrent risk (PCR) and typical concurrent risk (TCR) using regression coefficients. RESULTS: For fair/poor SRH, highest odds were associated with COPD. For mortality, highest odds were associated with dementia, hip fracture, and kidney disease. Dementia and hip fracture were associated with highest odds of ADL disability. Hispanic respondents had highest odds of ADL disability. Hispanic and NH Black respondents had higher odds of fair/poor SRH, ADL disability, and mortality. PCRs/TCRs demonstrated wide variability for respondents with similar sociodemographic-multimorbidity profiles. DISCUSSION: These findings highlight the variability of personalized risk in examining interdependent outcomes among older adults.

Development and validation of a prediction model for persistent functional impairment among older ICU survivors.

BACKGROUND: Critical illness often leads to persistent functional impairment among older Intensive Care Unit (ICU) survivors. Identification of high-risk survivors prior to discharge from their ICU hospitalization can facilitate targeting for restorative interventions after discharge, potentially improving the likelihood of functional recovery. Our objective was to develop and validate a prediction model for persistent functional impairment among older adults in the year after an ICU hospitalization. METHODS: The analytic sample included community-living participants enrolled in the National Health and Aging Trends Study 2011 cohort who survived an ICU hospitalization through December 2017 and had a follow-up interview within 1 year. Persistent functional impairment was defined as failure to recover to the pre-ICU level of function within 12 months of discharge from an ICU hospitalization. We used Bayesian model averaging to identify the final predictors from a comprehensive set of 17 factors. Discrimination and calibration were assessed using area-under-the-curve (AUC) and calibration plots. RESULTS: The development cohort included 456 ICU admissions (2,654,685 survey-weighted admissions) and the validation cohort included 227 ICU admissions (1,350,082 survey-weighted admissions). In the development cohort, the median age was 81.0 years (interquartile range [IQR] 76.0, 86.0) and 231 (50.7%) participants were women; demographic characteristics were comparable in the validation cohort. The rates of persistent functional impairment were 49.3% (development) and 50.2% (validation). The final model included age, pre-ICU disability, probable dementia, frailty, prior hospitalizations, vision impairment, depressive symptoms, and hospital length of stay. The model demonstrated good discrimination (AUC 71%, 95% confidence interval [CI] 0.66-0.76) and good calibration. When applied to the validation cohort, the model demonstrated comparable discrimination (AUC 72%, 95% CI 0.66-0.78) and good calibration. CONCLUSIONS: Application of the model prior to discharge from an ICU hospitalization may identify older adults at the highest risk of persistent functional impairment in the subsequent year, thereby facilitating targeted interventions and follow-up.

Platelet response to influenza vaccination reflects effects of aging.

Platelets are uniquely positioned as mediators of not only hemostasis but also innate immunity. However, how age and geriatric conditions such as frailty influence platelet function during an immune response remains unclear. We assessed the platelet transcriptome at baseline and following influenza vaccination in Younger (age 21-35) and Older (age ≥65) adults (including community-dwelling individuals who were largely non-frail and skilled nursing facility (SNF)-resident adults who nearly all met criteria for frailty). Prior to vaccination, we observed an age-associated increase in the expression of platelet activation and mitochondrial RNAs and decrease in RNAs encoding proteins mediating translation. Age-associated differences were also identified in post-vaccination response trajectories over 28 days. Using tensor decomposition analysis, we found increasing RNA expression of genes in platelet activation pathways in young participants, but decreasing levels in (SNF)-resident adults. Translation RNA trajectories were inversely correlated with these activation pathways. Enhanced platelet activation was found in community-dwelling older adults at the protein level, compared to young individuals both prior to and post-vaccination; whereas SNF residents showed decreased platelet activation compared to community-dwelling older adults that could reflect the influence of decreased translation RNA expression. Our results reveal alterations in the platelet transcriptome and activation responses that may contribute to age-associated chronic inflammation and the increased incidence of thrombotic and pro-inflammatory diseases in older adults.

High-throughput functional analysis of autism genes in zebrafish identifies convergence in dopaminergic and neuroimmune pathways.

Advancing from gene discovery in autism spectrum disorders (ASDs) to the identification of biologically relevant mechanisms remains a central challenge. Here, we perform parallel in vivo functional analysis of 10 ASD genes at the behavioral, structural, and circuit levels in zebrafish mutants, revealing both unique and overlapping effects of gene loss of function. Whole-brain mapping identifies the forebrain and cerebellum as the most significant contributors to brain size differences, while regions involved in sensory-motor control, particularly dopaminergic regions, are associated with altered baseline brain activity. Finally, we show a global increase in microglia resulting from ASD gene loss of function in select mutants, implicating neuroimmune dysfunction as a key pathway relevant to ASD biology.

Factors associated with retention on medications for opioid use disorder among a cohort of adults seeking treatment in the community.

BACKGROUND: Medication treatment for opioid use disorder (OUD) (MOUD; buprenorphine and methadone) reduces opioid use and overdose. Discontinuation of MOUD can quickly lead to relapse, overdose and death. Few persons who initiate MOUD are retained on treatment, thus it is critical to identify factors associated with retention. METHODS: Evaluated data was from an ongoing prospective cohort study of adults aged 18 or older with DSM-5 moderate to severe OUD seeking MOUD in the community and followed for 6 months. Participants were considered retained on MOUD through 6 months if they reported taking MOUD at every study interview without discontinuation. A high dose of MOUD was defined as a methadone dose > 85 mg or buprenorphine dose ≥ 16 mg. Multivariable logistic regression was conducted to assess factors associated with 6-month MOUD retention. RESULTS: A total of 118 participants (73% male, 58% white, 36% with HIV) were included. Buprenorphine was initiated by 58% and 42% started methadone. MOUD retention was 49% and 58% among buprenorphine and methadone, respectively, at 6-months. In adjusted models, a high MOUD dose (OR = 4.71, 95% CI 2.05-10.84) and higher pain interference (OR = 1.59, 95% CI 1.15-2.19) was associated with MOUD retention. CONCLUSIONS: Adequate dosing of MOUD leads to improved retention on MOUD. Further, persons with high pain interference at baseline had higher odds of retention on MOUD. Both methadone and buprenorphine have analgesic effects, thus those with high pain interference could have dual benefits of MOUD for treating OUD and pain. Interventions should be tailored to improve adequate MOUD dosing to improve retention on MOUD.

Population-Based Estimates of 1-Year Mortality After Major Surgery Among Community-Living Older US Adults.

Importance: Despite their importance to guiding public health decision-making and policies and to establishing programs aimed at improving surgical care, contemporary nationally representative mortality data for geriatric surgery are lacking. Objective: To calculate population-based estimates of mortality after major surgery in community-living older US adults and to determine how these estimates differ according to key demographic, surgical, and geriatric characteristics. Design, Setting, and Participants: Prospective longitudinal cohort study with 1 year of follow-up in the continental US from 2011 to 2018. Participants included 5590 community-living fee-for-service Medicare beneficiaries, aged 65 years or older, from the National Health and Aging Trends Study (NHATS). Data analysis was conducted from February 22, 2021, to March 16, 2022. Main Outcomes and Measures: Major surgeries and mortality over 1 year were identified through linkages with data from the Centers for Medicare & Medicaid Services. Data on frailty and dementia were obtained from the annual NHATS assessments. Results: From 2011 to 2017, of the 1193 major surgeries (from 992 community-living participants), the mean (SD) age was 79.2 (7.1) years; 665 were women (55.7%), and 30 were Hispanic (2.5%), 198 non-Hispanic Black (16.6%), and 915 non-Hispanic White (76.7%). Over the 1-year follow-up period, there were 206 deaths representing 872 096 survey-weighted deaths and 13.4% (95% CI, 10.9%-15.9%) mortality. Mortality rates were 7.4% (95% CI, 4.9%-9.9%) for elective surgeries and 22.3% (95% CI, 17.4%-27.1%) for nonelective surgeries. For geriatric subgroups, 1-year mortality was 6.0% (95% CI, 2.6%-9.4%) for persons who were nonfrail, 27.8% (95% CI, 21.2%-34.3%) for those who were frail, 11.6% (95% CI, 8.8%-14.4%) for persons without dementia, and 32.7% (95% CI, 24.3%-41.0%) for those with probable dementia. The age- and sex-adjusted hazard ratios for 1-year mortality were 4.41 (95% CI, 2.53-7.69) for frailty with a reduction in restricted mean survival time of 48.8 days and 2.18 (95% CI, 1.40-3.40) for probable dementia with a reduction in restricted mean survival time of 44.9 days. Conclusions and Relevance: In this study, the population-based estimate of 1-year mortality after major surgery among community-living older adults in the US was 13.4% but was 3-fold higher for nonelective than elective procedures. Mortality was considerably elevated among older persons who were frail or who had probable dementia, highlighting the potential prognostic value of geriatric conditions after major surgery.

Maintenance on extended-release naltrexone is associated with reduced injection opioid use among justice-involved persons with opioid use disorder.

INTRODUCTION: Opioid use disorder (OUD) and injection drug use (IDU) place justice-involved individuals at increased risk for acquiring or transmitting HIV or hepatitis C virus (HCV). Methadone and buprenorphine have been associated with reduced opioid IDU; however, the effect of extended-release naltrexone (XR-NTX) on this behavior is incompletely studied. METHODS: This study examined injection opioid use and shared injection equipment behavior from a completed double-blind placebo-controlled trial of XR-NTX among 88 justice-involved participants with HIV and OUD. Changes in participants' self-reported daily injection opioid use and shared injection equipment was evaluated pre-incarceration, during incarceration, and monthly post-release for 6 months. The study also assessed differences in time to first opioid injection post-release. The research team performed intention to treat and "as treated" (high treatment versus low treatment) analyses. RESULTS: Fifty-eight of 88 participants (69.5 %) endorsed IDU and 26 (29.5 %) reported sharing injection equipment in the 30 days pre-incarceration; 2 participants (2.2 %) reported IDU during incarceration; 19 (21.6 %) reported IDU one month post-release from prison or jail. Fifty-four (61.4 %) participants had an HIV RNA below 200 copies/mL and 62 (70.5 %) were baseline HCV antibody positive. The 6-month follow-up rate was 49.5 % and 50.5 % for those who received XR-NTX and placebo, respectively, which was not significantly different (p = 0.822). Participants in the XR-NTX and placebo groups had similar low mean opioid injection use post-release and time to first injection opioid use in the Intention-to-treat analysis. In the as-treated analysis, participants in the high treatment group had significantly lower mean proportion of days injecting opioids (13.8 % high treatment versus 22.8 % low treatment, p = 0.02) by month 1, which persisted up to 5 months post-release (0 % high treatment vs 24.3 % low treatment, p < 0.001) and experienced a longer time to first opioid injection post-release (143.8 days high treatment vs 67.4 days low treatment, p < 0.001). CONCLUSIONS: Injection opioid use was low during incarceration and remained low post-release in this justice-involved population. Retention on XR-NTX was associated with reduced intravenous opioid use, which has important implications for reducing transmission of HIV and HCV.

Evaluation of the Impact of HIV Serostatus on the Hepatitis C Virus Care Cascade and Injection Drug Use Among Persons Initiating Medication Treatment for Opioid Use Disorder.

Background: Persons who inject drugs are at increased risk for acquiring hepatitis C virus (HCV). Medications for opioid use disorder (MOUD) are associated with reduced injection drug use (IDU) frequency among persons with opioid use disorder (OUD). However, whether HCV treatment uptake or changes in IDU frequency differ by HIV serostatus among persons receiving MOUD is incompletely understood. Methods: A secondary analysis was performed of data collected from 2 prospective cohort studies of participants with (PWH) or without HIV with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition-diagnosed OUD who were initiated on methadone, buprenorphine, or naltrexone. Results: Of 129 participants, 78 (60.5%) were HCV antibody positive. PWH underwent increased HCV viral load testing (76.7% vs 43.3%; P = .028), but HCV treatment rates did not differ (17.6% vs 10.0%; P = .45) by HIV status. Participants without HIV reported a greater reduction in mean opioid IDU at 90 days (10.7 vs 2.0 fewer days out of 30; P < .001), but there were no group differences at 90 days. Stimulant use did not differ between groups. Urine opioid positivity declined from baseline to 90 days among the entire cohort (61.4% to 38.0%; P < .001) but did not differ by HIV serostatus. Conclusions: PWH who received MOUD underwent higher rates of follow-up HCV testing, but HCV treatment rates did not significantly differ by HIV serostatus. Participants without HIV on MOUD reported a greater reduction in opioid IDU. Improved integration of concomitant OUD with HCV and HIV screening, linkage to care, and treatment are needed for persons without HIV.

Association of entorhinal cortical tau deposition and hippocampal synaptic density in older individuals with normal cognition and early Alzheimer's disease.

Sites of early neuropathologic change provide important clues regarding the initial clinical features of Alzheimer's disease (AD). We have shown significant reductions in hippocampal synaptic density in participants with AD, consistent with the early degeneration of entorhinal cortical (ERC) cells that project to hippocampus via the perforant path. In this study, [11C]UCB-J binding to synaptic vesicle glycoprotein 2A (SV2A) and [18F]flortaucipir binding to tau were measured via PET in 10 participants with AD (5 mild cognitive impairment, 5 mild dementia) and 10 cognitively normal participants. In the overall sample, ERC tau was inversely associated with hippocampal synaptic density (r = -0.59, p = 0.009). After correction for partial volume effects, the association of ERC tau with hippocampal synaptic density was stronger in the overall sample (r = -0.61, p = 0.007) and in the AD group where the effect size was large, but not statistically significant (r = -0.58, p = 0.06). This inverse association of ERC tau and hippocampal synaptic density may reflect synaptic failure due to tau pathology in ERC neurons projecting to the hippocampus.