Amy Justice

Background Estimating the medical complexity of people aging with HIV can inform clinical programs and policy to meet future healthcare needs. The objective of our study was to forecast the prevalence of comorbidities and multimorbidity among people with HIV (PWH) using antiretroviral therapy (ART) in the United States (US) through 2030. Methods and findings Using the PEARL model—an agent-based simulation of PWH who have initiated ART in the US—the prevalence of anxiety, depression, stage ≥3 chronic kidney disease (CKD), dyslipidemia, diabetes, hypertension, cancer, end-stage liver disease (ESLD), myocardial infarction (MI), and multimorbidity (≥2 mental or physical comorbidities, other than HIV) were forecasted through 2030. Simulations were informed by the US CDC HIV surveillance data of new HIV diagnosis and the longitudinal North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) data on risk of comorbidities from 2009 to 2017. The simulated population represented 15 subgroups of PWH including Hispanic, non-Hispanic White (White), and non-Hispanic Black/African American (Black/AA) men who have sex with men (MSM), men and women with history of injection drug use and heterosexual men and women. Simulations were replicated for 200 runs and forecasted outcomes are presented as median values (95% uncertainty ranges are presented in the Supporting information). In 2020, PEARL forecasted a median population of 670,000 individuals receiving ART in the US, of whom 9% men and 4% women with history of injection drug use, 60% MSM, 8% heterosexual men, and 19 …

Objective:Examine the association between prior SARS-CoV-2 infection, interval from infection to surgery, and adverse surgical outcomes.Summary Background Data:Earlier series have reported worse outcomes for surgery after COVID-19 illness, and these findings have led to routinely deferring surgery seven weeks after infection.Methods:We created a retrospective cohort of patients from US Veterans Health Administration facilities nationwide, April 2020-September 2022, undergoing surgical procedures. Primary outcomes were 90-day all-cause mortality and 30-day complications. Within surgical procedure groupings, SARS-CoV-2 infected and uninfected patients were matched in a 1: 4 ratio. We categorized patients by two-week intervals from SARS-CoV-2 positive test to surgery. Hierarchical multilevel multivariable logistic regression models were used to estimate the association between infection to surgery …

BackgroundSurvival in pancreatic ductal adenocarcinoma (PDAC) remains poor due to late diagnosis. Electronic Health Records (EHRs) can be used to study this rare disease, but validated algorithms to identify PDAC in the United States EHRs do not currently exist.AimsTo develop and validate an algorithm using Veterans Health Administration (VHA) EHR data for the identification of patients with PDAC.MethodsWe developed two algorithms to identify patients with PDAC in the VHA from 2002 to 2023. The algorithms required diagnosis of exocrine pancreatic cancer in either ≥ 1 or ≥ 2 of the following domains: (i) the VA national cancer registry, (ii) an inpatient encounter, or (iii) an outpatient encounter in an oncology setting. Among individuals identified with ≥ 1 of the above criteria, a random sample of 100 were reviewed by three gastroenterologists to adjudicate PDAC status. We also adjudicated fifty …

BackgroundAn electronic health record–based tool could improve accuracy and eliminate bias in provider estimation of the risk of death from other causes among men with nonmetastatic cancer.ObjectiveTo recalibrate and validate the Veterans Aging Cohort Study Charlson Comorbidity Index (VACS-CCI) to predict non–prostate cancer mortality (non-PCM) and to compare it with a tool predicting prostate cancer mortality (PCM).Design, setting, and participantsAn observational cohort of men with biopsy-confirmed nonmetastatic prostate cancer, enrolled from 2001 to 2018 in the national US Veterans Health Administration (VA), was divided by the year of diagnosis into the development (2001–2006 and 2008–2018) and validation (2007) sets.Outcome measurements and statistical analysisMortality (all cause, non-PCM, and PCM) was evaluated. Accuracy was assessed using calibration curves and C statistic in the …

Existing outpatient parenteral antibiotic therapy (OPAT) registries are resource intensive, and OPAT programs struggle to produce objective data to show the value of their work. We describe the building and validation of an automated OPAT registry within our electronic medical record and provide objective data on the value of the program. Variables and outcomes include age, sex, race, ethnicity, primary insurance payor, antibiotic names, infection syndromes treated, discharge disposition, 30-day all-cause readmission and death rates, complications, and an estimate of the hospital days saved. Records for 146 OPAT episodes were reviewed manually to validate the registry. Data were displayed in a dashboard within the electronic medical record. Over the 4-year time frame, our registry collected 3956 unique patients who completed 4710 episodes (approximately 1200 episodes per year). A total of 400 …

Chronic pain is a common problem, with more than one-fifth of adult Americans reporting pain daily or on most days. It adversely affects the quality of life and imposes substantial personal and economic costs. Efforts to treat chronic pain using opioids had a central role in precipitating the opioid crisis. Despite an estimated heritability of 25–50%, the genetic architecture of chronic pain is not well-characterized, in part because studies have largely been limited to samples of European ancestry. To help address this knowledge gap, we conducted a cross-ancestry meta-analysis of pain intensity in 598,339 participants in the Million Veteran Program, which identified 126 independent genetic loci, 69 of which are new. Pain intensity was genetically correlated with other pain phenotypes, level of substance use and substance use disorders, other psychiatric traits, education level and cognitive traits. Integration of the …

Introduction The prevalence of pulmonary impairments in older adults is increasing, especially in those living with multiple chronic conditions, and is associated with mortality. We examined whether the addition of pulmonary measures improves all-cause mortality prediction of the Veterans Aging Cohort Study (VACS) Index 2.0 and the updated VACS index with Charlson Comorbidity Index (VACS-CCI) among Veterans. Methods We included patients in care in the Veterans Affairs Health System with pulmonary function tests (PFTs) in 2013 (baseline), determined using CPT codes. We used a previously developed Structured Query Language (SQL) algorithm to extract diffusion capacity for carbon monoxide (% DLCO) and forced expiratory volume in one second (% FEV1) from clinical notes of patients with PFTs. Numeric percent predicted values immediately following the key terms were extracted if they were within …

Opioid addiction constitutes a public health crisis in the United States and opioids cause the most drug overdose deaths in Americans. Yet, opioid addiction treatments have limited efficacy. To help address this problem, we used network-based machine learning techniques to integrate results from genome-wide association studies (GWAS) of opioid use disorder and problematic prescription opioid misuse with transcriptomic, proteomic, and epigenetic data from the dorsolateral prefrontal cortex (dlPFC) in opioid overdose victims. We identified 211 highly interrelated genes identified by GWAS or dysregulation in the dlPFC of individuals with opioid overdose victims that implicated the Akt, BDNF, and ERK pathways, identifying 414 drugs targeting 48 of these opioid addiction-associated genes. This included drugs used to treat other substance use disorders and antidepressant drugs. Our synthesis of multi-omics using a systems biology approach revealed key gene targets that could contribute to drug repurposing, genetics-informed addiction treatment, and future discovery.

Introduction As people age with HIV (PWH), many comorbid diseases are more common than among age matched comparators without HIV (PWoH). While the Veterans Aging Cohort (VACS) Index 2.0 accurately predicts mortality in PWH using age and clinical biomarkers, the only included comorbidity is hepatitis C. We asked whether adding comorbid disease groupings from the Charlson Comorbidity Index (CCI) improves the accuracy of VACS Index. Methods To maximize our ability to model mortality among older age groups, we began with PWoH in Veterans Health Administration (VA) from 2007–2017, divided into development and validation samples. Baseline predictors included age, and components of CCI and VACS Index (excluding CD4 count and HIV RNA). Patients were followed until December 31, 2021. We used Cox models to develop the VACS-CCI score and estimated mortality using a parametric (gamma) survival model. We compared accuracy using C-statistics and calibration curves in validation overall and within subgroups (gender, age Results The analytic sample consisted of 6,588,688 PWoH and 30,539 PWH. Among PWoH/PWH, median age was 65/55 years; 6%/3% were women; 15%/48% were Black and 5%/7% Hispanic. VACS-CCI provided the best discrimination (C-statistic = 0.81) with excellent calibration (predicted and observed mortality largely overlapped) overall and within subgroups. When VACS-CCI was applied to PWH it demonstrated similar discrimination as VACS Index 2.0 (C-statistic = 0.77 for both) but superior calibration among those with CD4 < 200. Discrimination was improved when CD4 …

Design:Retrospective cohort study.Objective:We sought to examine whether disruptions in follow-up intervals contributed to hypertension control.Background:Disruptions in health care were widespread during the coronavirus disease 2019 pandemic.Patients and Methods:We identified a cohort of individuals with hypertension in both prepandemic (March 2019–February 2020) and pandemic periods (March 2020–February 2022) in the Veterans Health Administration. First, we calculated follow-up intervals between the last prepandemic and first pandemic blood pressure measurement during a primary care clinic visit, and between measurements in the prepandemic period. Next, we estimated the association between the maintenance of (or achieving) hypertension control and the period using generalized estimating equations. We assessed associations between follow-up interval and control separately for periods …

Before combination therapy for HIV infection became available in the late 1990s, life expectancy after an AIDS diagnosis was measured in months. Combination antiretroviral therapy (ART) now allows people with HIV (PWH) to age, often living several decades after diagnosis. However, aging with HIV is different than aging without HIV. PWH are exposed to the combined effects of age-related diseases and the extended impact of HIV and its treatment. Many PWH also continue to smoke, drink alcohol, and use cannabis and other substances as they age, further complicating the aging process. Prolonged HIV infection, multimorbidity, polypharmacy, and multi-substance use, all increase susceptibility to age-related conditions and to adverse effects of medication. As a result, PWH are experiencing earlier onset of geriatric syndromes including cognitive compromise, falls and fractures, and frailty. Further, marginalized …

The rate of suicide among people with HIV (PWH) remains elevated compared to the general population. The aim of the study was to examine the association between a broad range of risk factors, HIV-specific risk factors, and suicide. We conducted a nested case-control study using data from the Veterans Aging Cohort Study (VACS) between 2006 and 2015. The risk of suicide was estimated using conditional logistic regression and models were stratified by HIV status. Most risk factors associated with suicide were similar between PWH and people without HIV; these included affective disorders, use of benzodiazepines, and mental health treatment. Among PWH, HIV-specific risk factors were not associated with suicide. A multiplicative interaction was observed between a diagnosis of HIV and a previous suicide attempt. Among PWH, a high prevalence of psychiatric, substance use disorders and multimorbidity …

We present an ensemble transfer learning method to predict suicide from Veterans Affairs (VA) electronic medical records (EMR). A diverse set of base models was trained to predict a binary outcome constructed from reported suicide, suicide attempt, and overdose diagnoses with varying choices of study design and prediction methodology. Each model used twenty cross-sectional and 190 longitudinal variables observed in eight time intervals covering 7.5 years prior to the time of prediction. Ensembles of seven base models were created and fine-tuned with ten variables expected to change with study design and outcome definition in order to predict suicide and combined outcome in a prospective cohort. The ensemble models achieved c-statistics of 0.73 on 2-year suicide risk and 0.83 on the combined outcome when predicting on a prospective cohort of  4.2 M veterans. The ensembles rely on nonlinear base …

Antiretroviral therapy has dramatically increased the lifespan of people living with HIV (PLWH), but advance care planning (ACP) and hospice services are underutilized in this population. The purpose of this study was to understand barriers and facilitators to ACP among this group. PLWH (n = 25) were recruited from an HIV Clinic at a Veterans Affairs (VA) Medical Center in Atlanta, GA to represent a range of sociodemographic characteristics and experiences. Semi-structured interviews were analyzed using thematic analysis. More than half of participants (64%) indicated not engaging in ACP. We identified four key barriers to ACP: (1) a self-image among PLWH as “survivors” (and a reluctance to think about ACP); (2) a history of mistrust and mistreatment; (3) weak social ties and a desire to avoid disclosure of HIV status; and (4) a value for self-reliance. Findings have important implications for interventions to …

The compilation and analysis of radiological images poses numerous challenges for researchers. The sheer volume of data as well as the computational needs of algorithms capable of operating on images are extensive. Additionally, the assembly of these images alone is difficult, as these exams may differ widely in terms of clinical context, structured annotation available for model training, modality, and patient identifiers. In this paper, we describe our experiences and challenges in establishing a trusted collection of radiology images linked to the United States Department of Veterans Affairs (VA) electronic health record database. We also discuss implications in making this repository research-ready for medical investigators. Key insights include uncovering the specific procedures required for transferring images from a clinical to a research-ready environment, as well as roadblocks and bottlenecks in this process that may hinder future efforts at automation.

Background Management of hypertension, dyslipidemia, diabetes and other modifiable factors may mitigate the cardiovascular disease (CVD) risk in people with human immunodeficiency virus (HIV, PWH) compared with people without HIV (PWoH). Methods This was a retrospective cohort study of 8285 PWH and 170 517 PWoH from an integrated health system. Risk factor control was measured using a novel disease management index (DMI) accounting for amount/duration above treatment goals (0% to 100% [perfect control]), including 2 DMIs for hypertension (diastolic and systolic blood pressure), 3 for dyslipidemia (low-density lipoprotein, total cholesterol, triglycerides), and 1 for diabetes (HbA1c). CVD risk by HIV status was evaluated overall and in subgroups defined by DMIs, smoking, alcohol use, and overweight/obesity in adjusted Cox proportional hazards models …

Antiretroviral therapy has dramatically increased the lifespan of people living with HIV (PLWH), but advance care planning (ACP) and hospice services are underutilized in this population. The purpose of this study was to understand barriers and facilitators to ACP among this group. PLWH (n= 25) were recruited from an HIV Clinic at a Veterans Affairs (VA) Medical Center in Atlanta, GA to represent a range of sociodemographic characteristics and experiences. Semi-structured interviews were analyzed using thematic analysis. More than half of participants (64%) indicated not engaging in ACP. We identified four key barriers to ACP:(1) a self-image among PLWH as" survivors"(and a reluctance to think about ACP);(2) a history of mistrust and mistreatment;(3) weak social ties and a desire to avoid disclosure of HIV status; and (4) a value for self-reliance. Findings have important implications for interventions to overcome these barriers.

Background Epigenome-wide association studies (EWAS) have identified CpG sites associated with HIV infection in blood cells in bulk, which offer limited knowledge of cell-type specific methylation patterns associated with HIV infection. In this study, we aim to identify differentially methylated CpG sites for HIV infection in immune cell types: CD4+ T-cells, CD8+ T-cells, B cells, Natural Killer (NK) cells, and monocytes. Methods Applying a computational deconvolution method, we performed a cell-type based EWAS for HIV infection in three independent cohorts (Ntotal = 1,382). DNA methylation in blood or in peripheral blood mononuclear cells (PBMCs) was profiled by an array-based method and then deconvoluted by Tensor Composition Analysis (TCA). The TCA-computed CpG methylation in each cell type was first benchmarked by bisulfite DNA methylation capture sequencing in a subset of the samples. Cell-type EWAS of HIV infection was performed in each cohort separately and a meta-EWAS was conducted followed by gene set enrichment analysis. Results The meta-analysis unveiled a total of 2,021 cell-type unique significant CpG sites for five inferred cell types. Among these inferred cell-type unique CpG sites, the concordance rate in the three cohorts ranged from 96% to 100% in each cell type. Cell-type level meta-EWAS unveiled distinct patterns of HIV-associated differential CpG methylation, where 74% of CpG sites were unique to individual cell types (false discovery rate, FDR <0.05). CD4+ T-cells had the largest number of unique HIV-associated CpG sites (N = 1,624) compared to any other cell type. Genes harboring significant …

Background: Collection of accurate Hispanic ethnicity data is critical to evaluate disparities in health and health care. However, this information is often inconsistently recorded in electronic health record (EHR) data. Objective: To enhance capture of Hispanic ethnicity in the Veterans Affairs EHR and compare relative disparities in health and health care. Methods: We first developed an algorithm based on surname and country of birth. We then determined sensitivity and specificity using self-reported ethnicity from the 2012 Veterans Aging Cohort Study survey as the reference standard and compared this to the research triangle institute race variable from the Medicare administrative data. Finally, we compared demographic characteristics and age-adjusted and sex-adjusted prevalence of conditions in Hispanic patients among different identification methods in the Veterans Affairs EHR 2018-2019. Results: Our …

Recent evidence suggests that aldosterone and its main receptor, the mineralocorticoid receptor (MR), modulate alcohol seeking and consumption. Therefore, the MR antagonist spironolactone may represent a novel pharmacotherapy for alcohol use disorder (AUD). In a series of rodent experiments, we tested the effects of spironolactone in a mouse model of alcohol drinking (drinking-in-the-dark) and in a rat model of alcohol dependence (vapor exposure). We also investigated the association between spironolactone receipt for at least 60 continuous days and change in self-reported alcohol consumption, using the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), in a pharmacoepidemiologic cohort study in the largest integrated healthcare system in the US. Spironolactone dose-dependently reduced the intake of sweetened or unsweetened alcohol solutions in male and female mice. No effects …