Julie A. Womack

Increased Risk of Fragility Fractures among HIV Infected Compared to Uninfected Male Veterans

Background HIV infection has been associated with an increased risk of fragility fracture. We explored whether or not this increased risk persisted in HIV infected and uninfected men when controlling for traditional fragility fracture risk factors. Methodology/Principal Findings Cox regression models were used to assess the association of HIV infection with the risk for incident hip, vertebral, or upper arm fracture in male Veterans enrolled in the Veterans Aging Cohort Study Virtual Cohort (VACS-VC). We calculated adjusted hazard ratios comparing HIV status and controlling for demographics and other established risk factors. The sample consisted of 119,318 men, 33% of whom were HIV infected (34% aged 50 years or older at baseline, and 55% black or Hispanic). Median body mass index (BMI) was lower in HIV infected compared with uninfected men (25 vs. 28 kg/m2; p<0.0001). Unadjusted risk for fracture was higher among HIV infected compared with uninfected men [HR: 1.32 (95% CI: 1.20, 1.47)]. After adjusting for demographics, comorbid disease, smoking and alcohol abuse, HIV infection remained associated with an increased fracture risk [HR: 1.24 (95% CI: 1.11, 1.39)]. However, adjusting for BMI attenuated this association [HR: 1.10 (95% CI: 0.97, 1.25)]. The only HIV-specific factor associated with fragility fracture was current protease inhibitor use [HR: 1.41 (95% CI: 1.16, 1.70)]. Conclusions/Significance HIV infection is associated with fragility fracture risk. This risk is attenuated by BMI.

A Proposal for Quality Standards for Measuring Medication Adherence in Research

A decade after widespread recognition that adherence to medication regimens is key to antiretroviral effectiveness, considerable controversy remains regarding a “gold standard” for adherence measurement. Each adherence measurement approach has strengths and weaknesses and each rests on specific assumptions. The range of assumptions regarding adherence measurement and the diversity with which each approach is implemented strongly suggest that the evaluation of a particular measure outside of the context in which it was used (e.g. the study’s operational protocol) may result in undeserved confidence or lack of confidence in study results. The purpose of this paper is to propose a set of best practices across commonly used measurement methods. Recommendations regarding what information should be included in published reports regarding how adherence was measured are provided to promote improvement in the quality of measurement of medication adherence in research.ResumenUna década después del reconocimiento generalizado que la adherencia a los regímenes de medicación es fundamental para la efectividad del tratamiento antirretroviral (ARV), se mantiene una gran controversia con respecto al “patrón oro” para la calculación de adherencia. Cada método de calculación de adherencia tiene fortalezas y debilidades y cada uno se basa en suposiciones específicas. La variedad de suposiciones sobre la calculación de adherencia y la diversidad con la cual cada método es implementado, encarecidamente sugiere que la evaluación de un método en particular fuera del contexto del cual se utiliza (por ejemplo el protocolo operativo del estudio) puede resultar en confianza inmerecida o falta de confianza en los resultados del estudio. El propósito de este manuscrito es proponer una serie de las mejores prácticas de métodos de calculación comúnmente utilizados. Las recomendaciones respecto a la información que se debe incluir en los informes publicados acerca de cómo la adherencia fue calculada, son proporcionados para promover mejoría en la calidad de la calculación de adherencia al régimen de medicación en estudios de investigación.

Physiologic Frailty and Fragility Fracture in HIV-Infected Male Veterans

BACKGROUND The Veterans Aging Cohort Study (VACS) Index is associated with all-cause mortality in individuals infected with human immunodeficiency virus (HIV). It is also associated with markers of inflammation and may thus reflect physiologic frailty. This analysis explores the association between physiologic frailty, as assessed by the VACS Index, and fragility fracture. METHODS HIV-infected men from VACS were included. We identified hip, vertebral, and upper arm fractures using ICD-9-CM codes. We used Cox regression models to assess fragility fracture risk factors including the VACS Index, its components (age, hepatitis C status, FIB-4 score, estimated glomerular filtration rate, hemoglobin, HIV RNA, CD4 count), and previously identified risk factors for fragility fractures. RESULTS We included 40 115 HIV-infected male Veterans. They experienced 588 first fragility fractures over 6.0 ± 3.9 years. The VACS Index score (hazard ratio [HR], 1.15; 95% confidence interval [CI], 1.11-1.19), white race (HR, 1.92; 95% CI, 1.63-2.28), body mass index (HR, 0.94; 95% CI, .92-.96), alcohol-related diagnoses (HR, 1.65; 95% CI, 1.26-2.17), cerebrovascular disease (HR, 1.95; 95% CI, 1.14-3.33), proton pump inhibitor use (HR, 1.87; 95% CI, 1.54-2.27), and protease inhibitor use (HR, 1.25; 95% CI, 1.04-1.50) were associated with fracture risk. Components of the VACS Index score most strongly associated with fracture risk were age (HR, 1.40; 95% CI, 1.27-1.54), log HIV RNA (HR, 0.91; 95% CI, .88-.94), and hemoglobin level (HR, 0.82; 95% CI, .78-.86). CONCLUSIONS Frailty, as measured by the VACS Index, is an important predictor of fragility fractures among HIV-infected male Veterans.

The Yale cTAKES extensions for document classification: architecture and application.

BACKGROUND Open-source clinical natural-language-processing (NLP) systems have lowered the barrier to the development of effective clinical document classification systems. Clinical natural-language-processing systems annotate the syntax and semantics of clinical text; however, feature extraction and representation for document classification pose technical challenges. METHODS The authors developed extensions to the clinical Text Analysis and Knowledge Extraction System (cTAKES) that simplify feature extraction, experimentation with various feature representations, and the development of both rule and machine-learning based document classifiers. The authors describe and evaluate their system, the Yale cTAKES Extensions (YTEX), on the classification of radiology reports that contain findings suggestive of hepatic decompensation. RESULTS AND DISCUSSION The F(1)-Score of the system for the retrieval of abdominal radiology reports was 96%, and was 79%, 91%, and 95% for the presence of liver masses, ascites, and varices, respectively. The authors released YTEX as open source, available at http://code.google.com/p/ytex.

Pregnancy and Mental Health Among Women Veterans Returning from Iraq and Afghanistan

BACKGROUND Veterans of Operations Enduring Freedom and Iraqi Freedom (OEF/OIF) may experience significant stress during military service that can have lingering effects. Little is known about mental health problems or treatment among pregnant OEF/OIF women veterans. The aim of this study was to determine the prevalence of mental health problems among veterans who received pregnancy-related care in the Veterans Health Administration (VHA) system. METHODS Data from the Defense Manpower Data Center (DMDC) deployment roster of military discharges from October 1, 2001, through April 30, 2008, were used to assemble an administrative cohort of female OEF/OIF veterans enrolled in care at the VHA (n = 43,078). Pregnancy and mental health conditions were quantified according to ICD-9-CM codes and specifications. Mental healthcare use and prenatal care were assessed by analyzing VHA stop codes. RESULTS During the study period, 2966 (7%) women received at least one episode of pregnancy-related care, and 32% of veterans with a pregnancy and 21% without a pregnancy received one or more mental health diagnoses (p < 0.0001). Veterans with a pregnancy were twice as likely to have a diagnosis of depression, anxiety, posttraumatic stress disorder (PTSD), bipolar disorder, or schizophrenia as those without a pregnancy. CONCLUSIONS Women OEF/OIF veterans commonly experience mental health problems after military service. The burden of mental health conditions is higher among women with an identified instance of pregnancy than among those without. Because women do not receive pregnancy care at the VHA, however, little is known about ongoing concomitant prenatal and mental healthcare or about pregnancy outcomes among these women veterans.

HIV Infection and Cardiovascular Disease in Women

Background HIV infection is associated with increased risk of cardiovascular disease (CVD) in men. Whether HIV is an independent risk factor for CVD in women has not yet been established. Methods and Results We analyzed data from the Veterans Aging Cohort Study on 2187 women (32% HIV infected [HIV+]) who were free of CVD at baseline. Participants were followed from their first clinical encounter on or after April 01, 2003 until a CVD event, death, or the last follow‐up date (December 31, 2009). The primary outcome was CVD (acute myocardial infarction [AMI], unstable angina, ischemic stroke, and heart failure). CVD events were defined using clinical data, International Classification of Diseases, Ninth Revision, Clinical Modification codes, and/or death certificate data. We used Cox proportional hazards models to assess the association between HIV and incident CVD, adjusting for age, race/ethnicity, lipids, smoking, blood pressure, diabetes, renal disease, obesity, hepatitis C, and substance use/abuse. Median follow‐up time was 6.0 years. Mean age at baseline of HIV+ and HIV uninfected (HIV−) women was 44.0 versus 43.2 years (P<0.05). Median time to CVD event was 3.1 versus 3.7 years (P=0.11). There were 86 incident CVD events (53%, HIV+): AMI, 13%; unstable angina, 8%; ischemic stroke, 22%; and heart failure, 57%. Incident CVD/1000 person‐years was significantly higher among HIV+ (13.5; 95% confidence interval [CI]=10.1, 18.1) than HIV− women (5.3; 95% CI=3.9, 7.3; P<0.001). HIV+ women had an increased risk of CVD, compared to HIV− (hazard ratio=2.8; 95% CI=1.7, 4.6; P<0.001). Conclusions HIV is associated with an increased risk of CVD in women.

An adapted frailty-related phenotype and the VACS index as predictors of hospitalization and mortality in HIV-infected and uninfected individuals.

Background:Frailty is a geriatric syndrome of decreased physiologic reserve and a risk factor for hospitalization and mortality. We hypothesized that an adapted survey-based frailty-related phenotype (aFRP) predicts hospitalization and mortality among HIV-infected and uninfected individuals in adjusted models but is uncommon among those achieving undetectable HIV-1 RNA. Methods:Defined from self-reported domains of physical shrinking, exhaustion, slowness, and low physical activity in Veterans Aging Cohort Study (VACS) participants, aFRP was considered present with ≥3 domains and prefrailty with 1–2 domains. Cox survival analysis determined hazard ratios (HRs) for 5-year hospitalization and mortality risk adjusting for frailty states, demographics, health behaviors, comorbidities, and a validated risk index incorporating HIV-specific and general organ system biomarkers, the VACS Index. Model discrimination was assessed. Results:Participants with complete data were included [6515/7324 (89%)]. Of these, 3.9% of HIV-infected individuals with HIV-1 RNA >400 copies per milliliter; 2.0% of HIV-infected individuals with HIV-1 RNA ⩽400 copies per milliliter; and 2.8% of uninfected individuals met aFRP criteria (P = 0.01). After adjustment for other covariates, aFRP was associated with hospitalization (HR = 1.78; 95% confidence interval: 1.48 to 2.13) and mortality (HR = 1.75; 95% confidence interval: 1.28 to 2.40). C-statistics for the VACS Index for hospitalization (0.633) and for mortality (0.756) were higher than for aFRP (0.565 and 0.584, respectively). C-statistic for hospitalization improved modestly when VACS Index and aFRP were both included (0.646) and minimally for mortality (0.761). Conclusions:aFRP was independently associated with adverse health outcomes among HIV-infected and uninfected individuals. aFRP modestly improved prediction for hospitalization. However, the aFRP is rare among HIV-infected individuals with undetectable HIV-1 RNA.

The musculoskeletal diagnosis cohort: Examining pain and pain care among veterans

Abstract Musculoskeletal disorders (MSDs) are highly prevalent, painful, and costly disorders. The MSD Cohort was created to characterize variation in pain, comorbidities, treatment, and outcomes among patients with MSD receiving Veterans Health Administration care across demographic groups, geographic regions, and facilities. We searched electronic health records to identify patients treated in Veterans Health Administration who had ICD-9-CM codes for diagnoses including, but not limited to, joint, back, and neck disorders, and osteoarthritis. Cohort inclusion criteria were 2 or more outpatient visits occurring within 18 months of one another or one inpatient visit with an MSD diagnosis between 2000 and 2011. The first diagnosis is the index date. Pain intensity numeric rating scale (NRS) scores, comorbid medical and mental health diagnoses, pain-related treatments, and other characteristics were collected retrospectively and prospectively. The cohort included 5,237,763 patients; their mean age was 59, 6% were women, 15% identified as black, and 18% reported severe pain (NRS ≥ 7) on the index date. Nontraumatic joint disorder (27%), back disorder (25%), and osteoarthritis (21%) were the most common MSD diagnoses. Patients entering the cohort in recent years had more concurrent MSD diagnoses and higher NRS scores. The MSD Cohort is a rich resource for collaborative pain-relevant health service research.

Comparison of outpatient health care utilization among returning women and men veterans from Afghanistan and Iraq

BackgroundThe number of women serving in the United States military increased during Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF), leading to a subsequent surge in new women Veterans seeking health care services from the Veterans Administration (VA). The objective of this study was to examine gender differences among OEF/OIF Veterans in utilization of VA outpatient health care services.MethodsOur retrospective cohort consisted of 1,620 OEF/OIF Veterans (240 women and 1380 men) who enrolled for outpatient healthcare at a single VA facility. We collected demographic data and information on military service and VA utilization from VA electronic medical records. To assess gender differences we used two models: use versus nonuse of services (logistic regression) and intensity of use among users (negative binomial regression).ResultsIn our sample, women were more likely to be younger, single, and non-white than men. Women were more likely to utilize outpatient care services (odds ratio [OR] = 1.47, 95% confidence interval [CI]:1.09, 1.98), but once care was initiated, frequency of visits over time (intensity) did not differ by gender (incident rate ratio [IRR] = 1.07; 95% CI: 0.90, 1.27).ConclusionRecently discharged OEF/OIF women Veterans were more likely to seek VA health care than men Veterans. But the intensity of use was similar between women and men VA care users. As more women use VA health care, prospective studies exploring gender differences in types of services utilized, health outcomes, and factors associated with satisfaction will be required.

Perceptions of Barriers and Facilitators During Implementation of a Complex Model of Group Prenatal Care in Six Urban Sites

Group prenatal care improves perinatal outcomes, but implementing this complex model places substantial demands on settings designed for individual care. To describe perceived barriers and facilitators to implementing and sustaining CenteringPregnancy Plus (CP+) group prenatal care, 24 in-depth interviews were conducted with 22 clinicians, staff, administrators, and study personnel in six of the 14 sites of a randomized trial of the model. All sites served low-income, minority women. Sites for the present evaluation were selected for variation in location, study arm, and initial implementation response. Implementing CP+ was challenging in all sites, requiring substantial adaptations of clinical systems. All sites had barriers to meeting the models demands, but how sites responded to these barriers affected whether implementation thrived or struggled. Thriving sites had organizational cultures that supported innovation, champions who advocated for CP+, and staff who viewed logistical demands as manageable hurdles. Struggling sites had bureaucratic organizational structures and lacked buy-in and financial resources, and staff were overwhelmed by the models challenges. Findings suggested that implementing and sustaining health care innovation requires new practices and different ways of thinking, and health systems may not fully recognize the magnitude of change required. Consequently, evidence-based practices are modified or discontinued, and outcomes may differ from those in the original controlled studies. Before implementing new models of care, clinical settings should anticipate model demands and assess capacity for adapting to the disruptions of innovation.