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1.  Unhealthy Alcohol and Illicit Drug Use are Associated with Decreased Quality of HIV Care 
Background
HIV-infected patients with substance use experience suboptimal health outcomes, possibly to due to variations in care.
Objectives
To assess the association between substance use and the quality of HIV care (QOC) received.
Research Design
Retrospective cohort study.
Subjects
HIV-infected patients enrolled in the Veterans Aging Cohort Study.
Measures
We collected self-report substance use data and abstracted 9 HIV quality indicators (QIs) from medical records. Independent variables were unhealthy alcohol use (AUDIT-C score ≥4) and illicit drug use (self-report of stimulants, opioids, or injection drug use in past year). Main outcome was the percentage of QIs received, if eligible. We estimated associations between substance use and QOC using multivariable linear regression.
Results
The majority of the 3,410 patients were male (97.4%) and Black (67.0%) with a mean age of 49.1 years (SD 8.8). Overall, 25.8% reported unhealthy alcohol use, 22% illicit drug use, and participants received 81.5% (SD=18.9) of QIs. The mean percentage of QIs received was lower for those with unhealthy alcohol use vs. not (59.3% vs. 70.0%, p<.001) and those using illicit drugs vs. not (57.8% vs. 70.7%, p<.001). In multivariable models, unhealthy alcohol use (adjusted β −2.74; 95% CI −4.23, −1.25) and illicit drug use (adjusted β −3.51 95% CI −4.99, −2.02) remained inversely associated with the percentage of QIs received.
Conclusions
Though the overall QOC for these HIV-infected Veteran patients was high, gaps persist for those with unhealthy alcohol and illicit drug use. Interventions that address substance use in HIV-infected patients may improve the QOC received.
doi:10.1097/QAI.0b013e31826741aa
PMCID: PMC3460799  PMID: 22820808
Alcohol; Quality of Health Care; HIV; Quality Indicators; Health Care; Opioid-Related Disorders
2.  HIV Status, Burden of Comorbid Disease, and Biomarkers of Inflammation, Altered Coagulation, and Monocyte Activation 
We investigated the association between human immunodeficiency virus (HIV) and prevalence of elevated biomarkers of inflammation, altered coagulation, and monocyte activation in a cohort of HIV-infected and uninfected veterans who had a comparable burden of comorbid conditions.
Background. Biomarkers of inflammation, altered coagulation, and monocyte activation are associated with mortality and cardiovascular disease (CVD) in the general population and among human immunodeficiency virus (HIV)–infected people. We compared biomarkers for inflammation, altered coagulation, and monocyte activation between HIV-infected and uninfected people in the Veterans Aging Cohort Study (VACS).
Methods. Biomarkers of inflammation (interleukin-6 [IL-6]), altered coagulation (d-dimer), and monocyte activation (soluble CD14 [sCD14]) were measured in blood samples from 1525 HIV-infected and 843 uninfected VACS participants. Logistic regression was used to determine the association between HIV infection and prevalence of elevated (>75th percentile) biomarkers, adjusting for confounding comorbidities.
Results. HIV-infected veterans had less prevalent CVD, hypertension, diabetes, obesity, hazardous drinking, and renal disease, but more dyslipidemia, hepatitis C, and current smoking than uninfected veterans. Compared to uninfected veterans, HIV-infected veterans with HIV-1 RNA ≥500 copies/mL or CD4 count <200 cells/µL had a significantly higher prevalence of elevated IL-6 (odds ratio [OR], 1.54; 95% confidence interval [CI],1.14–2.09; OR, 2.25; 95% CI, 1.60–3.16, respectively) and d-dimer (OR, 1.97; 95% CI, 1.44–2.71, OR, 1.68; 95% CI, 1.22–2.32, respectively) after adjusting for comorbidities. HIV-infected veterans with a CD4 cell count <200 cells/µL had significantly higher prevalence of elevated sCD14 compared to uninfected veterans (OR, 2.60; 95% CI, 1.64–4.14). These associations still persisted after restricting the analysis to veterans without known confounding comorbid conditions.
Conclusions. These data suggest that ongoing HIV replication and immune depletion significantly contribute to increased prevalence of elevated biomarkers of inflammation, altered coagulation, and monocyte activation. This contribution is independent of and in addition to the substantial contribution from comorbid conditions.
doi:10.1093/cid/cis406
PMCID: PMC3493182  PMID: 22534147
3.  Hepatic safety and antiretroviral effectiveness in HIV-infected patients receiving naltrexone 
Background
We sought to determine the impact of naltrexone on hepatic enzymes and HIV biomarkers in HIV-infected patients.
Methods
We used data from the Veterans Aging Cohort Study-Virtual Cohort, an electronic database of administrative, pharmacy and laboratory data. We restricted our sample to HIV-infected patients who received an initial oral naltrexone prescription, of at least seven days duration. We examined aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and HIV biomarker (CD4 and HIV RNA) values for the 365 days prior to, during, and for the 365 days post-naltrexone prescription. We also examined cases of liver enzyme elevation (LEE; defined as greater than 5 times baseline ALT or AST or greater than 3.5 times baseline if baseline ALT or AST was greater than or equal to 40 IU/L).
Results
Of 114 HIV-infected individuals, 97% were male, 65% white, 57% Hepatitis C co-infected, median age was 49 years; 89% of the sample had a history of alcohol dependence and 32% had opioid dependence. Median duration of naltrexone prescription was 49 (interquartile range 30–83) days, representing 9,525 person-days of naltrexone use. Mean ALT and AST levels remained below the upper limit of normal. Two cases of LEE occurred. Mean CD4 count remained stable and mean HIV RNA decreased after naltrexone prescription.
Conclusions
In HIV-infected patients, oral naltrexone is rarely associated with clinically significant ALT or AST changes and does not have a negative impact on biologic parameters. Therefore, HIV-infected patients with alcohol or opioid dependence can be treated with naltrexone.
doi:10.1111/j.1530-0277.2011.01601.x
PMCID: PMC3221963  PMID: 21797892
4.  Validating Smoking Data From the Veteran’s Affairs Health Factors Dataset, an Electronic Data Source 
Nicotine & Tobacco Research  2011;13(12):1233-1239.
Introduction:
We assessed smoking data from the Veterans Health Administration (VHA) electronic medical record (EMR) Health Factors dataset.
Methods:
To assess the validity of the EMR Health Factors smoking data, we first created an algorithm to convert text entries into a 3-category smoking variable (never, former, and current). We compared this EMR smoking variable to 2 different sources of patient self-reported smoking survey data: (a) 6,816 HIV-infected and -uninfected participants in the 8-site Veterans Aging Cohort Study (VACS-8) and (b) a subset of 13,689 participants from the national VACS Virtual Cohort (VACS-VC), who also completed the 1999 Large Health Study (LHS) survey. Sensitivity, specificity, and kappa statistics were used to evaluate agreement of EMR Health Factors smoking data with self-report smoking data.
Results:
For the EMR Health Factors and VACS-8 comparison of current, former, and never smoking categories, the kappa statistic was .66. For EMR Health Factors and VACS-VC/LHS comparison of smoking, the kappa statistic was .61.
Conclusions:
Based on kappa statistics, agreement between the EMR Health Factors and survey sources is substantial. Identification of current smokers nationally within the VHA can be used in future studies to track smoking status over time, to evaluate smoking interventions, and to adjust for smoking status in research. Our methodology may provide insights for other organizations seeking to use EMR data for accurate determination of smoking status.
doi:10.1093/ntr/ntr206
PMCID: PMC3223583  PMID: 21911825
5.  A Comparison of Treatment Eligibility for Hepatitis C Virus in HCV-Monoinfected Versus HCV/HIV-Coinfected Persons in Electronically Retrieved Cohort of HCV-Infected Veterans 
Abstract
Treatment rates for hepatitis C virus (HCV) are low in actual clinical settings. However, the proportion of patients eligible for treatment, especially among those coinfected with HIV, is not well known. Our aim was to determine and compare the rates for HCV treatment eligibility among HCV and HCV-HIV-coinfected persons. We assembled a national cohort of HCV-infected veterans in care from 1998–2003, using the VA National Patient Care Database for demographic/clinical information, the Pharmacy Benefits Management database for pharmacy records, and the Decision Support Systems database for laboratory data. We compared the HCV-monoinfected and HCV-HIV-coinfected subjects for treatment indications and eligibility using current treatment guidelines. Of the 27,452 subjects with HCV and 1225 with HCV-HIV coinfection, 74.0% and 84.6% had indications for therapy and among these, 43.9% of HCV-monoinfected and 28.4% of HCV-HIV-coinfected subjects were eligible for treatment. Anemia, decompensated liver disease (DLD), chronic obstructive pulmonary disease (COPD), recent alcohol abuse, and coronary artery disease were the most common contraindications in the HCV, and anemia, DLD, renal failure, recent drug abuse, and COPD in the HCV-HIV-coinfected group. Among those eligible for treatment, only 23% of the HCV-monoinfected and 15% of the HCV-HIV-coinfected subjects received any treatment for HCV. Most veterans with HCV are not eligible for treatment according to the current guidelines. Even for those who are eligible for treatment, only a minority is prescribed treatment. Several contraindications are modifiable and aggressive management of those may improve treatment prescription rates.
doi:10.1089/aid.2011.0004
PMCID: PMC3719436  PMID: 21338329
6.  Food Insecurity is Associated with Poor Virologic Response among HIV-Infected Patients Receiving Antiretroviral Medications 
Journal of General Internal Medicine  2011;26(9):1012-1018.
ABSTRACT
BACKGROUND AND OBJECTIVE
Food insecurity negatively impacts HIV disease outcomes in international settings. No large scale U.S. studies have investigated the association between food insecurity and severity of HIV disease or the mechanism of this possible association. The objective of this study was to examine the impact of food insecurity on HIV disease outcomes in a large cohort of HIV-infected patients receiving antiretroviral medications.
DESIGN
This is a cross-sectional study.
PARTICIPANTS AND SETTING
Participants were HIV-infected patients enrolled in the Veterans Aging Cohort Study between 2002–2008 who were receiving antiretroviral medications.
MAIN MEASUREMENTS
Participants reporting “concern about having enough food for you or your family in the past 30 days” were defined as food insecure. Using multivariable logistic regression, we explored the association between food insecurity and both low CD4 counts (<200 cells/μL) and unsuppressed HIV-1 RNA (>500 copies/mL). We then performed mediation analysis to examine whether antiretroviral adherence or body mass index mediates the observed associations.
KEY RESULTS
Among 2353 HIV-infected participants receiving antiretroviral medications, 24% reported food insecurity. In adjusted analyses, food insecure participants were more likely to have an unsuppressed HIV-1 RNA (AOR 1.37, 95% CI 1.09, 1.73) compared to food secure participants. Mediation analysis revealed that neither antiretroviral medication adherence nor body mass index contributes to the association between food insecurity and unsuppressed HIV-1 RNA. Food insecurity was not independently associated with low CD4 counts.
CONCLUSIONS
Among HIV-infected participants receiving antiretroviral medications, food insecurity is associated with unsuppressed viral load and may render treatment less effective. Longitudinal studies are needed to test the potential causal association between food insecurity, lack of virologic suppression, and additional HIV outcomes.
doi:10.1007/s11606-011-1723-8
PMCID: PMC3157515  PMID: 21573882
food insecurity; HIV; patients; antiretrovirals
7.  The Risk of Incident Coronary Heart Disease Among Veterans with and without HIV and Hepatitis C 
Background
Whether hepatitis C (HCV) confers additional coronary heart disease (CHD) risk among Human Immunodeficiency Virus (HIV) infected individuals is unclear. Without appropriate adjustment for antiretroviral therapy, CD4 count, and HIV-1 RNA, and substantially different mortality rates among those with and without HIV and HCV infection, the association between HIV, HCV, and CHD may be obscured.
Methods and Results
We analyzed data on 8579 participants (28% HIV+, 9% HIV+HCV+) from the Veterans Aging Cohort Study Virtual Cohort who participated in the 1999 Large Health Study of Veteran Enrollees. We analyzed data collected on HIV and HCV status, risk factors for and the incidence of CHD, and mortality from 1/2000–7/2007. We compared models to assess CHD risk when death was treated as a censoring event and as a competing risk. During the median 7.3 years of follow-up, there were 194 CHD events and 1186 deaths. Compared with HIV−HCV− Veterans, HIV+ HCV+ Veterans had a significantly higher risk of CHD regardless of whether death was adjusted for as a censoring event (adjusted hazard ratio (HR)=2.03, 95% CI=1.28–3.21) or a competing risk (adjusted HR=2.45, 95% CI=1.83–3.27 respectively). Compared with HIV+HCV− Veterans, HIV+ HCV+ Veterans also had a significantly higher adjusted risk of CHD regardless of whether death was treated as a censored event (adjusted HR=1.93, 95% CI=1.02–3.62) or a competing risk (adjusted HR =1.46, 95% CI=1.03–2.07).
Conclusions
HIV+HCV+ Veterans have an increased risk of CHD compared to HIV+HCV−, and HIV−HCV− Veterans.
doi:10.1161/CIRCOUTCOMES.110.957415
PMCID: PMC3159506  PMID: 21712519
viruses; coronary disease; mortality; multi morbidity
9.  Hepatitis C treatment completion rates in routine clinical care 
Background
Treatment completion rates for hepatitis C virus (HCV) infection in clinical practice settings are unknown.
Methods
We assembled a national cohort of HCV-infected veterans-in-care from 1998 to 2003, using the VA National Patient Care Database for demographical/clinical information, Pharmacy Benefits Management database for pharmacy records and the Decision Support Systems database for laboratory data. We used logistic regression to determine the factors predicting treatment non-completion for HCV.
Results
We identified 134 934 HCV-infected veterans of whom 16 043 [11.9%; 95% confidence interval (CI) 11.7–12.1] were prescribed treatment for HCV. Among the 10 641 veterans with > 1 year of follow-up, 2396 (22.5%; 95% CI 21.7–23.3) completed a 48-week course. Non-completers were more likely to have pre-treatment anaemia, coronary artery disease, depression, substance abuse, used standard interferon, higher comorbidity count, and been treated at a low-volume treatment site (defined as sites initiating HCV treatment for < 200 individuals). In multivariable analyses, treatment completion was positively associated with pegylated interferon use [odds ratio (OR) 1.59, 95% CI 1.40–1.80] and site treatment volume (OR 1.87, 95% CI 1.56–2.24 for sites initiating treatment for > 200 individuals) and negatively associated with pre-treatment anaemia (OR 0.68, 95% CI 0.58–0.80 for haemoglobin 10–14 g/dl) and depression (OR 0.78, 95% CI 0.69–0.89). Human immunodeficiency virus coinfection and minority race were not associated with failing to complete treatment.
Conclusions
Among veterans-in-care with known HCV, 11.9% initiate therapy of whom 22.5% (one in 56 with known HCV infection) complete a 48-week course of treatment. Higher completion rates among higher volume treatment sites suggest that some factors associated with non-completion (pre-treatment depression and anaemia), may be modifiable with experience.
doi:10.1111/j.1478-3231.2009.02156.x
PMCID: PMC3132089  PMID: 19889081
anaemia; depression; hepatitis C; HIV infection; pegylated interferon; practice variation; treatment completion
10.  An Experimental Study of the Agreement of Self-Administration and Telephone Administration of the Timeline Followback Interview* 
Objective
The Timeline Followback (TLFB) interview has become state-of-the-science for the collection of retrospective self-reports of daily alcohol consumption. Such data are especially useful for addressing questions of the co-occurrence of quantity of alcohol consumption and other behaviors, such as HIV-related risky sex, on the event level. The purpose of this study was to determine if the TLFB could be used effectively by self-administration compared with the more costly telephone interview in a large, multisite observational study of HIV-positive and HIV-negative adults.
Method
An experimental design was used to compare self-administered and telephone-administered TLFB modes in a subsample (N = 70) of the Veterans Aging Cohort Study, an ongoing longitudinal study of more than 6,000 HIV-positive and HIV-negative men and women presenting for treatment at eight Department of Veterans Affairs Infectious Disease or General Medicine clinics. Participants were randomly assigned to one of four experimental groups defined by mode and sequence of a TLFB administration on two occasions occurring within 1 week: telephone-telephone, telephone-self, self-telephone, and self-self.
Results
Analyses showed no differences in median total number of drinks reported between modes of TLFB administration or sequence of mode of administration. The same findings held for classification of participants as “hazardous” drinkers. Additional analyses showed good-to-excellent test-retest reliability of self-reports for both modes of TLFB administration.
Conclusions
The data derived from this study provide strong experimental evidence for the utility of the self-administered, 30-day TLFB in collecting daily alcohol consumption in large observational studies of HIV-positive and HIV-negative individuals.
PMCID: PMC3115624  PMID: 18432391
11.  Adjusting Alcohol Quantity for Mean Consumption and Intoxication Threshold Improves Prediction of Nonadherence in HIV Patients and HIV-Negative Controls 
Background
Screening for hazardous drinking may fail to detect a substantial proportion of individuals harmed by alcohol. We investigated whether considering an individual’s usual drinking quantity or threshold for alcohol-induced cognitive impairment improves the prediction of nonadherence with prescribed medications.
Method
Cross-sectional analysis of participants in a large, multi-site cohort study. We used the timeline followback to reconstruct 30-day retrospective drinking histories and the timeline followback modified for adherence to reconstruct 30-day medication adherence histories among 3,152 individuals in the Veterans Aging Cohort Study, 1,529 HIV infected and 1,623 uninfected controls. We categorized daily alcohol consumption by using quantity alone, quantity after adjustment for the individual’s mean daily alcohol consumption, and self-reported level of impairment corresponding to each quantity. A standard drink was defined as 14 g of ethanol. Nonadherence was defined as the proportion of days with ≥1 medication doses missed or taken ≥2 hours late, and clinically significant nonadherence was defined as ≥5% absolute increase in the proportion of days with nonadherence.
Results
The mean adjusted- and impairment-based methods showed greater discrimination of nonadherence risk compared to the measure based on quantity alone (quantity-based categorization, 3.2-fold increase; quantity adjusted for mean daily consumption, 4.6-fold increase, impairment-based categorization, 3.6-fold increase). The individualized methods also detected greater numbers of days with clinically significant nonadherence associated with alcohol. Alcohol was associated with clinically significant nonadherence at a lower threshold for HIV infected versus uninfected patients (2 standard drinks vs. 4 standard drinks) using quantity-based categorization, but this difference was no longer apparent when individualized methods were used.
Conclusions
Tailoring screening questions to an individual’s usual level of alcohol consumption or threshold for impairment improves the ability to predict alcohol-associated medication nonadherence.
doi:10.1111/j.1530-0277.2008.00732.x
PMCID: PMC3111093  PMID: 18616666
Human Immunodeficiency Virus; Alcohol; Nonadherence
12.  Factor Structure of Leigh’s (1990) Alcohol Sex Expectancies Scale in Individuals in Treatment for HIV Disease 
AIDS and behavior  2008;14(1):174-180.
The purpose of this study was to validate the use of Leigh’s (1990) alcohol sex expectancies scale among HIV-infected individuals presenting for treatment as a way to facilitate research on sexual risk reduction among individuals in that population. The participants were 944 men who presented for treatment at infectious disease or general medicine clinics across 8 different VA Medical Center sites. A total of 534 of these men were HIV-positive and 410 were HIV-negative. The total sample was randomly divided in half within each HIV group to form exploratory (Sample 1) and confirmatory (Sample 2) subsamples. A principal components factor analysis with oblique rotation of the original 13-item Leigh scale within each HIV group in Sample 1 revealed a 2-factor (7 and 4 items, respectively) solution that was consistent across both HIV groups. These factors were named “More Open to Sexual Pleasure” (Factor 1) and “Reduced Inhibitions about Sex (Factor 2).” A confirmatory factor analysis of the 11-item, 2-factor solution on the full Sample 2 showed a modest fit to the data, excellent internal consistency reliability of both factors, a high correlation between the factors, and strong evidence for construct validity. These results were interpreted as supporting the use of the 11-item, 2-factor version of Leigh’s scale in studies of clinical samples of HIV-positive adults, and directions for research on further scale refinement are discussed.
doi:10.1007/s10461-008-9457-2
PMCID: PMC3032495  PMID: 18791863
Leigh (1990) scale; Alcohol sex expectancies; HIV-positive; Validation
13.  Comparison of Two VA Laboratory Data Repositories Indicates That Missing Data Vary Despite Originating From the Same Source 
Medical care  2009;47(1):121-124.
Background
Assessing accuracy and completeness of data is an important component of conducting research. VA Healthcare System benefits from a highly developed electronic medical information system. The Immunology Case Registry was designed to monitor costs and quality of HIV care. The Decision Support System was developed to monitor utilization and costs of veterans in care. Because these systems extract data from the same source using independent methods, they provide an opportunity to compare the accuracy and completeness of each.
Objective
To compare overlapping laboratory data from the Veterans Affairs Health Information System between 2 data repositories.
Research Design
For hemoglobin, CD4+ lymphocyte counts (CD4), HIV RNA viral load, aspartate aminotransferase, alanine aminotransferase, glycosylated hemoglobin, creatinine, and white blood count, we calculated the percent of individuals with a value from each source. For results in both repositories, we calculated Pearson’s correlation coefficients.
Subjects
A total of 22,647 HIV + veterans in the Virtual Cohort with a visit in fiscal year 2002.
Results
For 6 out of 9 tests, 68% to 72% of the observations overlapped. For CD4, viral load, and glycosylated hemoglobin less than 31% of observations overlapped. Overlapping results were nearly perfectly correlated except for CD4.
Conclusions
Six of the laboratory tests demonstrated remarkably similar amounts of overlap, though Immunology Case Registry and Decision Support System both have missing data. Findings indicate that validation of laboratory data should be conducted before its use in quality and efficiency projects. When 2 databases are not available for comparison, other methods of validation should be implemented.
doi:10.1097/MLR.0b013e31817d69c2
PMCID: PMC3032537  PMID: 19106740
laboratory; DSS; ICR; VA
14.  Erectile Dysfunction Drug Receipt, Risky Sexual Behavior and Sexually Transmitted Diseases in HIV-infected and HIV-uninfected Men 
BACKGROUND
Health care providers may be concerned that prescribing erectile dysfunction drugs (EDD) will contribute to risky sexual behavior.
OBJECTIVES
To identify characteristics of men who received EDD prescriptions, determine whether EDD receipt is associated with risky sexual behavior and sexually transmitted diseases (STDs), and determine whether these relationships vary for certain sub-groups.
DESIGN
Cross-sectional study.
PARTICIPANTS
Two thousand seven hundred and eighty-seven sexually-active, HIV-infected and HIV-uninfected men recruited from eight Veterans Health Affairs outpatient clinics. Data were obtained from participant surveys, electronic medical records, and administrative pharmacy data.
MEASURES
EDD receipt was defined as two or more prescriptions for an EDD, risky sex as having unprotected sex with a partner of serodiscordant or unknown HIV status, and STDs, according to self-report.
RESULTS
Overall, 28% of men received EDD in the previous year. Eleven percent of men reported unprotected sex with a serodiscordant/unknown partner in the past year (HIV-infected 15%, HIV-uninfected 6%, P < 0.001). Compared to men who did not receive EDD, men who received EDD were equally likely to report risky sexual behavior (11% vs. 10%, p = 0.9) and STDs (7% vs 7%, p = 0.7). In multivariate analyses, EDD receipt was not significantly associated with risky sexual behavior or STDs in the entire sample or in subgroups of substance users or men who had sex with men.
CONCLUSION
EDD receipt was common but not associated with risky sexual behavior or STDs in this sample of HIV-infected and uninfected men. However, risky sexual behaviors persist in a minority of HIV-infected men, indicating ongoing need for prevention interventions.
doi:10.1007/s11606-009-1164-9
PMCID: PMC2837496  PMID: 19921112
HIV infection; risky sexual behavior; STDs; men; phosphodiesterase inhibitors
15.  The association between alcohol consumption and prevalent cardiovascular diseases among HIV infected and uninfected men 
Objective
To determine whether alcohol consumption is associated with cardiovascular disease (CVD) among HIV infected veterans
Methods
Using established thresholds for alcohol consumption, we analyzed cross-sectional data from 4743 men 51% HIV infected) from the Veterans Aging Cohort Study, a prospective cohort of HIV infected and demographically similar uninfected veterans. Using logistic regression, we estimated the odds ratio (OR) for the association between alcohol consumption and prevalent CVD.
Results
Among HIV infected and uninfected men respectively, hazardous drinking (33.2% vs. 30.9%,), alcohol abuse and dependence (20.9% vs. 26.2%), and CVD (14.6% vs. 19.8%) were common. Among HIV infected men, hazardous drinking (OR=1.43, 95% confidence interval (CI)=1.05-1.94) and alcohol abuse and dependence (OR=1.55, 95% CI=1.07-2.23) were associated with a higher prevalence of CVD compared with infrequent and moderate drinking. Among HIV uninfected men, past drinkers had a higher prevalence of CVD (OR=1.30, 95% CI=1.01-1.67). For HIV infected and uninfected men, traditional risk factors and kidney disease were associated with CVD.
Conclusions
Among HIV infected men, hazardous drinking and alcohol abuse and dependence were associated with a higher prevalence of CVD compared with infrequent and moderate drinking even after adjusting for traditional CVD risk factors, antiretroviral therapy, and CD 4 count.
doi:10.1097/QAI.0b013e3181c6c4b7
PMCID: PMC2858978  PMID: 20009766
alcohol consumption; alcohol abuse; alcohol dependence; HIV infection; cardiovascular disease; Veterans
16.  Regulation of Peroxisome Proliferator-Activated Receptor- β/δ by the APC/β-CATENIN Pathway and Nonsteroidal Antiinflammatory Drugs 
Molecular carcinogenesis  2009;48(10):942-952.
Studies indicate that peroxisome proliferator-activated receptor-β/δ (PPARb/δ) can either attenuate or potentiate colon cancer. One hypothesis suggests that PPARβ/δ is upregulated by the adenomatous polyposis coli (APC)/β-CATENIN pathway and a related hypothesis suggests that PPARβ/δ is downregulated by nonsteroidal anti-inflammatory drugs (NSAIDs). The present study examined these possibilities using in vivo and in vitro models. While APC/β-CATENIN-dependent expression of CYCLIN D1 was observed in vivo and in vitro, expression of PPARβ/δ was not different in colon or intestinal polyps from wild-type or Apcmin heterozygous mice or in human colon cancer cell lines with mutations in APC and/or β-CATENIN. No difference in the level of PPARβ/δ was found in colon from wild-type or Apcmin heterozygous mice following treatment with NO-donating aspirin (NO-ASA). NSAIDs inhibited cell growth in RKO (wild-type APC) and DLD1 (mutant APC) human colon cancer cell lines but expression of PPARβ/δ was not downregulated in these cell lines in response to a broad concentration range of celecoxib, indomethacin, NS-398, or nimesulide. However, indomethacin caused an increase in PPARβ/δ mRNA and protein that was accompanied with increased expression of a known PPARβ/δ target gene. Interestingly, expression of PPARα was also increased in the human colon cancer cell lines by several NSAIDs at the highest concentration examined. Results from these studies provide additional evidence indicating that PPARβ/δ is not upregulated by the APC/β-CATENIN pathway. Further, these studies suggest that increased PPARβ/δ and/or PPARα by NSAIDs in human colon cancer cell lines could contribute to the mechanisms underlying the chemopreventive effects of NSAIDs.
doi:10.1002/mc.20546
PMCID: PMC2790141  PMID: 19415698
colon cancer; PPARβ/δ; gene expression; NSAIDs
17.  Incidence of Non-AIDS-Defining Malignancies in HIV-Infected Vs. Non-Infected Patients in the HAART Era: Impact of Immunosuppression 
Background
The incidence of non-AIDS-defining malignancies (non-ADM) is reported as unchanged or increasing in the HAART era. Whether incidence of non-ADM is significantly higher in HIV-infected than in HIV-uninfected patients remains unclear.
Methods
Incidence rates of malignancies were calculated in a cohort of veterans in care for HIV-infected and age, race, and gender-matched uninfected patients from 1997 to 2004. For HIV-infected patients CD4 counts closest to first observation date were compared between those with and without cancer.
Results
33,420 HIV-infected and 66,840 HIV-uninfected patients were followed for a median of 5.1 and 6.4 years. The Incidence rate ratio [IRR] of HIV-infected to HIV-uninfected was 1.6 (1260 vs. 841/100,000 person-years; 95% CI: 1.5–1.7). IRR for individual cancers was highest for anal cancer (14.9; CI: 10.1–22.1). Among HIV-infected patients, median CD4 counts were lower for those with non-ADM (249 vs. 270, p=0.02), anal cancer (154 vs. 270; p<0.001), and Hodgkin’s (217 vs. 270; p=0.03). Prostate cancer was associated with a higher CD4 count (310 vs. 270; p<0.001).
Conclusions
In the HAART era, the incidence of non-ADMs is higher among HIV-infected than HIV-uninfected patients, adjusting for age, race, and gender. Some non-ADMs do not appear to be associated with significantly lower CD4 counts.
doi:10.1097/QAI.0b013e3181b033ab
PMCID: PMC2814969  PMID: 19617846
AIDS-defining malignancies; Non-AIDS-defining malignancies; Incidence; HAART
18.  HIV Infection and the Risk of Diabetes Mellitus 
AIDS (London, England)  2009;23(10):1227-1234.
Background
The influence of HIV infection on the risk of diabetes is unclear. We determined the association and predictors of prevalent DM in HIV infected and uninfected veterans.
Methods
We determined baseline prevalence and risk factors for diabetes among HIV infected and uninfected veterans in the Veterans Aging Cohort Study. Logistic regression was used to determine the odds of diabetes in HIV infected and uninfected persons.
Results
We studied 3,327 HIV-infected and 3,240 HIV-uninfected subjects. HIV infected subjects were younger, more likely to be black race, male, have HCV coinfection and a lower body mass index (BMI). HIV infected subjects had a lower prevalence of diabetes at baseline (14.9% vs. 21.4%, P<0.0001). After adjustment for known risk factors, HIV infected individuals had a lower risk of diabetes (OR 0.84, 95% CI 0.72-0.97). Increasing age, male gender, minority race, and BMI were associated with an increased risk. The odds ratio for diabetes associated with increasing age, minority race and BMI were greater among HIV infected veterans. HCV coinfection and nucleoside and non-nucleoside reverse transcriptase inhibitor therapy were associated with a higher risk of diabetes in HIV infected veterans.
Conclusion
While HIV infection itself is not associated with increased risk of diabetes, increasing age, HCV coinfection and BMI have a more profound effect upon the risk of diabetes among HIV infected persons. Further, long term ARV treatment also increases risk. Future studies will need to determine whether incidence of DM differs by HIV status.
doi:10.1097/QAD.0b013e32832bd7af
PMCID: PMC2752953  PMID: 19444074
HIV; diabetes; HCV; risk; antiretroviral therapy
19.  Dementia Patient Suffering and Caregiver Depression 
Cross-sectional and longitudinal analyses were carried out to assess the relationship between dementia patient suffering, caregiver depression, and antidepressant medication use in 1222 dementia patients and their caregivers. We assessed the prevalence of 2 types of patient suffering, emotional and existential distress, and examined their independent associations with caregiver depression and antidepressant medication use when controlling for sociodemographic characteristics of caregivers and patients, cognitive and physical disability of the patient, the frequency of patient memory problems and disruptive behaviors, and the amount of time spent caring for the patient. Multiple linear regression models showed that both aspects of perceived patient suffering independently contribute to caregiver depression (emotional distress: β = 1.24; P < 0.001; existential distress: β = 0.66; P < 0.01) whereas only existential suffering contributes to antidepressant medication use: odds ratio = 1.25 95% confidence interval, 1.10–1.42; P < 0.01. In longitudinal analyses, increases in both types of suffering were associated with increases in caregiver depression (emotional distress: β = 1.02; P < 0.01; existential distress: β = 0.64; P < 0.01). This is the first study to show in a large sample that perceived patient suffering independently contributes to family caregiver depression and medication use. Medical treatment of patients that maintain or improve memory but do not address suffering may have little impact on the caregiver. Alzheimer disease patient suffering should be systematically assessed and treated by clinicians.
doi:10.1097/WAD.0b013e31816653cc
PMCID: PMC2782456  PMID: 18525290
suffering; dementia; caregiving; depression; anti-depressant use
20.  The Impact of Cigarette Smoking on Mortality, Quality of Life, and Comorbid Illness Among HIV-Positive Veterans 
Journal of General Internal Medicine  2005;20(12):1142-1145.
Background
The impact of smoking on outcomes among those with HIV infection has not been determined in the era of highly active antiretroviral therapy (HAART).
Study Objective
Determine the impact of smoking on morbidity and mortality in HIV-positive patients post-HAART.
Design
Prospective observational study.
Participants
Eight hundred and sixty-seven HIV-positive veterans enrolled in the Veterans Aging Cohort 3 Site Study.
Measurements
Clinical data were collected through patient questionnaire, International Classification of Diseases—9th edition codes, and standardized chart extraction, and laboratory and mortality data through the national VA database. Quality of life was assessed with the physical component summary (PCS) of the Short-Form 12.
Results
Current smokers had increased respiratory symptoms, chronic obstructive pulmonary disease (COPD), and bacterial pneumonia. In analyses adjusted for age, race/ethnicity, CD4 cell count, HIV RNA level, hemoglobin, illegal drug and alcohol use, quality of life was substantially decreased (β=−3.3, 95% confidence interval [CI] −5.3 to −1.4) and mortality was significantly increased (hazard ratio 1.99, 95% CI 1.03 to 3.86) in current smokers compared with never smokers.
Conclusions
HIV-positive patients who currently smoke have increased mortality and decreased quality of life, as well as increased respiratory symptoms, COPD, and bacterial pneumonia. These findings suggest that smoking cessation should be emphasized for HIV-infected patients.
doi:10.1111/j.1525-1497.2005.0255.x
PMCID: PMC1490270  PMID: 16423106
HIV; AIDS; smoking; mortality; health-related quality of life
21.  Clinical Importance of HIV and Depressive Symptoms Among Veterans with HIV Infection 
OBJECTIVE
To compare the clinical importance (association with illness severity and survival) of depressive and HIV symptoms among veterans with HIV infection.
DESIGN
Cross-sectional study; survival analysis.
SETTING
Infectious Disease Clinics at 3 VA Medical Centers.
PARTICIPANTS
HIV-infected patients (N = 881) and their health care providers from June 1999 through July 2000.
MEASUREMENTS AND MAIN RESULTS
Depressive symptoms were assessed using the 10-item Centers for Epidemiologic Studies Depression Scale (CES-D). Patient baseline survey included an HIV Symptom Index measuring the frequency and bother of 20 common symptoms. Providers were surveyed on patients' illness severity, and survival data were obtained from VA death records. Of 881 patients, 46% had significant depressive symptoms (CES-D ≥10). Increasing depression symptom severity was associated with increasing HIV symptom frequency (P < .001) and bother (P < .001). Multiple regression results revealed that having moderate or severe depressive symptoms was not associated with provider-reported illness severity or survival. However, HIV symptoms were significantly associated with provider-reported illness severity (P < .01) and survival (P = .05), after adjusting for moderate and severe depressive symptoms, CD4 cell count/mm3, viral load, age, race, and antiretroviral use.
CONCLUSIONS
Depression, while common in this sample, was not associated with illness severity or mortality after adjusting for HIV symptoms. HIV symptoms are associated with severity of illness and survival regardless of patients' severity of depressive symptoms. This suggests that equal medical consideration should be given to HIV symptoms presented by HIV-infected patients regardless of their depression status, rather than automatically attributing medical complaints to depression.
doi:10.1046/j.1525-1497.2002.10803.x
PMCID: PMC1495073  PMID: 12133141
HIV/AIDS; symptoms; depression

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