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1.  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
2.  Alcohol Consumption and Depressive Symptoms Over Time: A Longitudinal Study of Patients With and Without HIV Infection 
Drug and alcohol dependence  2011;117(2-3):158-163.
Background
The impact of alcohol consumption on depressive symptoms over time among patients who do not meet criteria for alcohol abuse or dependence is not known.
Objective
To evaluate the impact of varying levels of alcohol consumption on depressive symptoms over time in patients with and without HIV infection.
Design
We used data from the Veterans Aging Cohort Study (VACS). We used generalized estimating equations models to assess the association of alcohol-related categories, as a fixed effect, on the time-varying outcome of depressive symptoms.
Participants
VACS is a prospectively enrolled cohort study of HIV-infected patients and age-, race- and site-matched HIV uninfected patients.
Main Measures
Hazardous, binge drinking, alcohol abuse and alcohol dependence were defined using standard criteria. Depressive symptoms were measured by the Patient Health Questionnaire (PHQ-9).
Key Results
Among the 2446 patients, 19% reported past but not current alcohol use, 50% non-hazardous drinking, 8% hazardous drinking, 14% binge drinking, and 10% met criteria for alcohol or dependence. At baseline, depressive symptoms were higher in hazardous and binge drinkers than in past and non-hazardous drinkers (OR=2.65; CI=1.50/4.69; p<.001) and similar to those with abuse or dependence. There was no difference in the association between alcohol-related category and depressive symptoms by HIV status (OR=0.99; CI=.83/1.18; p=.88). Hazardous drinkers were 2.53 (95% CI = 1.34/4.81) times and binge drinkers were 2.14 (95% CI = 1.49/3.07) times more likely to meet criteria for depression when compared to non-hazardous drinkers. The associations between alcohol consumption and depressive symptoms persisted over three years and were responsive to changes in alcohol-related categories.
Conclusions
HIV-infected and HIV-uninfected hazardous and binge drinkers have depressive symptoms that are more severe than non-hazardous and non-drinkers and similar to those with alcohol abuse or dependence. Patients who switch to a higher or lower level of drinking experience a similar alteration in their depressive symptoms. Interventions to decrease unhealthy alcohol consumption may improve depressive symptoms.
doi:10.1016/j.drugalcdep.2011.01.014
PMCID: PMC3113463  PMID: 21345624
Alcohol drinking; Alcoholism; Depression; Depressive disorder; HIV; Acquired Immunodeficiency Syndrome
3.  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
4.  Predictive Accuracy of the Veterans Aging Cohort Study (VACS) Index for Mortality with HIV Infection: A North American Cross Cohort Analysis 
Background
By supplementing an index composed of HIV biomarkers and age (Restricted Index) with measures of organ injury, the Veterans Aging Cohort Study (VACS) Index more completely reflects risk of mortality. We compare the accuracy of the VACS and Restricted Indices 1) among subjects outside the Veterans Healthcare System (VA), 2) over 1–5 years of prior exposure to antiretroviral therapy (ART), and 3) within important patient subgroups.
Methods
We used data from 13 cohorts in the North American AIDS Cohort Collaboration (NA-ACCORD, n=10, 835) limiting analyses to HIV-infected subjects with at least 12 months exposure to ART. Variables included demographic, laboratory (CD4 count, HIV-1 RNA, hemoglobin, platelets, aspartate and alanine transaminase, creatinine and hepatitis C status), and survival. We used C statistic and net reclassification improvement (NRI) to test discrimination varying prior ART exposure from 1–5 years. We then combined VA (n=5,066) and NA-ACCORD data, fit a parametric survival model, and compared predicted to observed mortality by cohort, gender, age, race, and HIV-1 RNA level.
Results
Mean follow-up was 3.3 years (655 deaths). Compared with the Restricted Index, the VACS Index showed greater discrimination (C statistic: 0.77 vs. 0.74; NRI 12%; p<0.0001). NRI was highest among those with HIV-1 RNA<500 copies/ml (25%) and age ≥50 years (20%). Predictions were similar to observed mortality among all subgroups.
Conclusion
VACS Index scores discriminate risk and translate into accurate mortality estimates over 1–5 years of exposures to ART and for diverse patient subgroups from North American
doi:10.1097/QAI.0b013e31827df36c
PMCID: PMC3619393  PMID: 23187941
HIV; Aging; Prognosis
5.  Risk of Heart Failure With Human Immunodeficiency Virus in the Absence of Prior Diagnosis of Coronary Heart Disease 
Archives of internal medicine  2011;171(8):737-743.
Background
Whether human immunodeficiency virus (HIV) infection is a risk factor for heart failure (HF) is not clear. The presence of coronary heart disease and alcohol consumption in this population may confound this association.
Methods
To determine whether HIV infection is a risk factor for incident HF, we conducted a population-based, retrospective cohort study of HIV-infected and HIV-uninfected veterans enrolled in the Veterans Aging Cohort Study Virtual Cohort (VACS-VC) and the 1999 Large Health Study of Veteran Enrollees (LHS) from January 1, 2000, to July 31, 2007.
Results
There were 8486 participants (28.2% HIV-infected) enrolled in the VACS-VC who also participated in the 1999 LHS. During the median 7.3 years of follow-up, 286 incident HF events occurred. Age- and race/ethnicity–adjusted HF rates among HIV-infected and HIV-uninfected veterans were 7.12 (95% confidence interval [CI],6.90-7.34) and 4.82 (95% CI, 4.72-4.91) per 1000 person-years, respectively. Compared with HIV-uninfected veterans, those who were HIV infected had an increased risk ofHF (adjusted hazard ratio [HR], 1.81; 95% CI, 1.39-2.36). This association persisted among veterans who did not have a coronary heart disease event or a diagnosis related to alcohol abuse or dependence before the incident HF event (adjusted HR, 1.96; 95% CI, 1.29-2.98). Compared with HIV-uninfected veterans, those who were HIV infected with a baseline Human immunodeficiency virus 1 (HIV-1) RNA level of 500 or more copies/mL had a higher risk of HF (adjusted HR, 2.28; 95% CI, 1.57-3.32), while those with baseline and a recent HIV-1 RNA level less than 500 copies/mL did not (adjusted HR, 1.10; 95% CI, 0.64-1.89; P< .001 for comparison between high and low HIV-1 RNA groups).
Conclusions
Our data suggest that HIV infection is a risk factor for HF. Ongoing viral replication is associated with a higher risk of developing HF.
doi:10.1001/archinternmed.2011.151
PMCID: PMC3687533  PMID: 21518940
6.  Sex Disparities in Overall Burden of Disease Among HIV-Infected Individuals in the Veterans Affairs Healthcare System 
Journal of General Internal Medicine  2013;28(Suppl 2):577-582.
ABSTRACT
BACKGROUND
Whether sex disparities exist in overall burden of disease among human immunodeficiency virus (HIV)-infected individuals in the Veterans Affairs healthcare system (VA) is unknown.
OBJECTIVE
To determine whether sex differences exist in overall burden of disease after 1 year of combined antiretroviral therapy (ART) among HIV-infected individuals in VA.
DESIGN
Retrospective cohort study.
PARTICIPANTS
Among patients in the Veterans Aging Cohort Study Virtual Cohort (VACS-VC), all ART-naïve HIV-infected Veterans who received VA-based HIV care between 1996 and 2009.
MAIN MEASURES
Overall burden of disease was measured using the VACS Index, an index that incorporates HIV (e.g. CD4 cell count) and non-HIV biomarkers (e.g. hemoglobin) and is highly predictive of all-cause mortality. Possible scores range from 0 to 164, although scores typically range from 0 to 50 for 80 % of patients in VACS-VC. A higher score indicates greater burden of disease (each additional five points indicates approximately 20 % increased 5-year mortality risk). ART adherence was measured using pharmacy data.
KEY RESULTS
Complete data were available for 227 women and 8,073 men. At ART initiation, compared with men, women were younger and more likely to be Black, less likely to have liver dysfunction, but more likely to have lower hemoglobin levels. Median VACS Index scores changed from ART initiation to 1 year after ART initiation: women’s scores went from 41 to 28 for women (13 point improvement) and men’s from 42 to 27 for men (15 point improvement). In multivariable regression, women had 3.6 point worse scores than men after 1 year on ART (p = 0.002); this difference decreased to 3.2 points after adjusting for adherence (p = 0.004).
CONCLUSIONS
In VA, compared to men, women experienced less improvement in overall burden of disease after 1 year of HIV treatment. Further study is needed to elucidate the modifiable factors that may explain this disparity.
doi:10.1007/s11606-013-2346-z
PMCID: PMC3695278  PMID: 23807068
women; Veterans; HIV; health care disparities; burden of illness
7.  Decreased Serum Antibody Responses to Recombinant Pneumocystis Antigens in HIV-Infected and Uninfected Current Smokers▿  
Serologic studies can provide important insights into the epidemiology and transmission of Pneumocystis jirovecii. Exposure to P. jirovecii can be assessed by serum antibody responses to recombinant antigens from the major surface glycoprotein (MsgC), although factors that influence the magnitude of the antibody response are incompletely understood. We determined the magnitudes of antibody responses to P. jirovecii in comparison to adenovirus and respiratory syncytial virus (RSV) in HIV-infected and uninfected patients and identified predictors associated with the magnitude of the response. We performed a cross-sectional analysis using serum samples and data from 153 HIV-positive and 92 HIV-negative subjects enrolled in a feasibility study of the Veterans Aging Cohort 5 Site Study (VACS 5). Antibodies were measured using an enzyme-linked immunosorbent assay (ELISA). Independent predictors of antibody responses were determined using multivariate Tobit regression models. The results showed that serum antibody responses to P. jirovecii MsgC fragments were significantly and independently decreased in current smokers. Antibodies to P. jirovecii also tended to be lower with chronic obstructive pulmonary disease (COPD), hazardous alcohol use, injection drug use, and HIV infection, although these results were not statistically significant. These results were specific to P. jirovecii and did not correlate with adenovirus. Antibody responses to RSV were in the inverse direction. Thus, current smoking was independently associated with decreased P. jirovecii antibody responses. Whether smoking exerts an immunosuppressive effect that affects the P. jirovecii antibody response, colonization, or subsequent risk for disease is unclear; prospective, longitudinal studies are needed to evaluate these findings further.
doi:10.1128/CVI.00421-10
PMCID: PMC3067379  PMID: 21191078
8.  Towards a combined prognostic index for survival in HIV infection: the role of ‘non-HIV’ biomarkers 
HIV medicine  2009;11(2):143-151.
Background
As those with HIV infection live longer, ‘non-AIDS’ condition associated with immunodeficiency and chronic inflammation are more common. We ask whether ‘non-HIV’ biomarkers improve differentiation of mortality risk among individuals initiating combination antiretroviral therapy (cART).
Methods
Using Poisson models, we analysed data from the Veterans Aging Cohort Study (VACS) on HIV-infected veterans initiating cART between 1 January 1997 and 1 August 2002. Measurements included: HIV biomarkers (CD4 cell count, HIV RNA and AIDS-defining conditions); ‘non-HIV’ biomarkers (haemoglobin, transaminases, platelets, creatinine, and hepatitis B and C serology); substance abuse or dependence (alcohol or drug); and age. Outcome was all cause mortality. We tested the discrimination (C statistics) of each biomarker group alone and in combination in development and validation data sets, over a range of survival intervals, and adjusting for missing data.
Results
Of veterans initiating cART, 9784 (72%) had complete data. Of these, 2566 died. Subjects were middle-aged (median age 45 years), mainly male (98%) and predominantly black (51%). HIV and ‘non-HIV’ markers were associated with each other (P<0.0001) and discriminated mortality (C statistics 0.68–0.73); when combined, discrimination improved (P<0.0001). Discrimination for the VACS Index was greater for shorter survival intervals [30-day C statistic 0.86, 95% confidence interval (CI) 0.80–0.91], but good for intervals of up to 8 years (C statistic 0.73, 95% CI 0.72–0.74). Results were robust to adjustment for missing data.
Conclusions
When added to HIV biomarkers, ‘non-HIV’ biomarkers improve differentiation of mortality. When evaluated over similar intervals, the VACS Index discriminates as well as other established indices. After further validation, the VACS Index may provide a useful, integrated risk assessment for management and research.
doi:10.1111/j.1468-1293.2009.00757.x
PMCID: PMC3077949  PMID: 19751364
anaemia; CD4 cell count; hepatitis C coinfection; hepatology; injecting drug use; outcomes; renal/kidney; risk groups; viral load
9.  Patterns of drug use and abuse among aging adults with and without HIV: A latent class analysis of a US Veteran cohort* 
Drug and alcohol dependence  2010;110(3):208-220.
This study characterized the extent and patterns self-reported drug use among aging adults with and without HIV, assessed differences in patterns by HIV status, and examined pattern correlates. Data derived from 6351 HIV infected and uninfected adults enrolled in an eight-site matched cohort, the Veterans Aging Cohort Study (VACS). Using clinical variables from electronic medical records and sociodemographics, drug use consequences, and frequency of drug use from baseline surveys, we performed latent class analyses (LCA) stratified by HIV status and adjusted for clinical and socio-demographic covariates. Participants were, on average, age 50 (range 22–86), primarily male (95%) and African-American (64%). Five distinct patterns emerged: non-users, past primarily marijuana users, past multidrug users, current high consequence multidrug users, and current low consequence primarily marijuana users. HIV status strongly influenced class membership. Non -users were most p revalent among HIV uninfected (36.4%) and current high consequence multidrug users (25.5%) were most prevalent among HIV infected. While problems of obesity marked those not currently u sing drugs, current users experienced higher prevalences of medical or mental health disorders. Multimorbidity was highest among past and current multidrug users. HIV-infected participants were more likely than HIV-uninfected participants to be current low consequence primarily marijuana users. In this sample, active drug use and abuse were common. HIV infected and uninfected Veterans differed on extent and patterns of drug use and on important characteristics within identified classes. Findings have the potential to inform screening and intervention efforts in aging drug users with and without HIV.
doi:10.1016/j.drugalcdep.2010.02.020
PMCID: PMC3087206  PMID: 20395074
aging; Veterans; HIV; substance-related disorders; latent class analysis; illicit drugs; cohort studies
10.  Does an Index Composed of Clinical Data Reflect Effects of Inflammation, Coagulation, and Monocyte Activation on Mortality Among Those Aging With HIV? 
The Veterans Aging Cohort Study (VACS) Index, based on age and 8 routine clinical tests, is strongly correlated with 3 biomarkers of inflammation: interleukin 6 (IL-6), D-dimer, and soluble CD14 (sCD14). After adjustment for the VACS Index, D-dimer and sCD14, but not IL-6, remain independently associated with mortality.
Background. When added to age, CD4 count and human immunodeficiency virus type 1 (HIV-1) RNA alone (Restricted Index), hemoglobin, FIB-4 Index, hepatitis C virus (HCV), and estimated glomerular filtration rate improve prediction of mortality. Weighted and combined, these 7 routine clinical variables constitute the Veterans Aging Cohort Study (VACS) Index. Because nonroutine biomarkers of inflammation (interleukin 6 [IL-6]), coagulation (D-dimer), and monocyte activation (sCD14) also predict mortality, we test the association of these indices and biomarkers with each other and with mortality.
Methods. Samples from 1302 HIV-infected veterans on antiretroviral therapy were analyzed. Indices were calculated closest to date of collection. We calculated Spearman correlations stratified by HIV-1 RNA and HCV status and measured association with mortality using C statistics and net reclassification improvement (NRI).
Results. Of 1302 subjects, 915 had HIV-1 RNA <500 copies/mL and 154 died. The VACS Index was more correlated with IL-6, D-dimer, and sCD14 than the Restricted Index (P < .001). It was also more predictive of mortality (C statistic, 0.76; 95% confidence interval [CI], .72–.80) than any biomarker (C statistic, 0.66–0.70) or the Restricted Index (C statistic, 0.71; 95% CI, .67–.75). Compared to the Restricted Index alone, NRI resulted from incremental addition of VACS Index components (10%), D-dimer (7%), and sCD14 (4%), but not from IL-6 (0%).
Conclusions. Among HIV-infected individuals, independent of CD4, HIV-1 RNA, and age, hemoglobin and markers of liver and renal injury are associated with inflammation. Addition of D-dimer and sCD14, but not IL-6, improves the predictive accuracy of the VACS Index for mortality.
doi:10.1093/cid/cir989
PMCID: PMC3297653  PMID: 22337823
11.  Association of Age and Comorbidity with Physical Function in HIV-Infected and Uninfected Patients: Results from the Veterans Aging Cohort Study 
AIDS Patient Care and STDs  2011;25(1):13-20.
Abstract
HIV clinical care now involves prevention and treatment of age-associated comorbidity. Although physical function is an established correlate to comorbidity in older adults without HIV infection, its role in aging of HIV-infected adults is not well understood. To investigate this question we conducted cross-sectional analyses including linear regression models of physical function in 3227 HIV-infected and 3240 uninfected patients enrolled 2002–2006 in the Veterans Aging Cohort Study-8-site (VACS-8). Baseline self-reported physical function correlated with the Short Form-12 physical subscale (ρ = 0.74, p < 0.001), and predicted survival. Across the age groups decline in physical function per year was greater in HIV-infected patients (βcoef −0.25, p < 0.001) compared to uninfected patients (βcoef −0.08, p = 0.03). This difference, although statistically significant (p < 0.01), was small. Function in the average 50-year old HIV-infected subject was equivalent to the average 51.5-year-old uninfected subject. History of cardiovascular disease was a significant predictor of poor function, but the effect was similar across groups. Chronic pulmonary disease had a differential effect on function by HIV status (Δβcoef −3.5, p = 0.03). A 50-year-old HIV-infected subject with chronic pulmonary disease had the equivalent level of function as a 68.1-year-old uninfected subject with chronic pulmonary disease. We conclude that age-associated comorbidity affects physical function in HIV-infected patients, and may modify the effect of aging. Longitudinal research with markers of disease severity is needed to investigate loss of physical function with aging, and to develop age-specific HIV care guidelines.
doi:10.1089/apc.2010.0242
PMCID: PMC3030913  PMID: 21214375
12.  Depression Symptoms and Treatment Among HIV Infected and Uninfected Veterans 
AIDS and behavior  2008;14(2):272-279.
Depression is one of the most common comorbid conditions affecting persons with HIV. We compared depressive symptoms and depression treatment using data from the Veterans Aging Cohort Study (VACS), a prospective cohort of HIV-infected and uninfected subjects. We identified subjects with a Patient Health Questionnaire score of 10 or greater. Treatment was defined as prescription of a selective serotonin reuptake inhibitor (SSRI) or mental health counseling. Overall, 16% of 4,480 subjects had depressive symptoms, and HIV-infected patients were more likely to have had depressive symptoms (OR = 1.38, 95% CI = 1.18, 1.62). Geographic site of care and having a mental health provider at the clinic was associated with treatment. In multivariable models restricted to 732 patients with depressive symptoms, receipt of depression treatment did not differ by HIV status (Adjusted OR = 1.11, 95% CI = 0.80, 1.54). Non-Hispanic whites were more likely to receive treatment (Adjusted OR = 2.09, 95% CI 1.04, 4.24). Primary care and HIV providers were equally unlikely to treat active depressive symptoms. Treatment variation by race, site, and availability of a mental health provider, suggests targets for intervention.
doi:10.1007/s10461-008-9428-7
PMCID: PMC3125603  PMID: 18648927
HIV-infection; Depression; Psychiatric status rating scales; Anti-depressive agents
13.  Increased Risk of Fragility Fractures among HIV Infected Compared to Uninfected Male Veterans 
PLoS ONE  2011;6(2):e17217.
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.
doi:10.1371/journal.pone.0017217
PMCID: PMC3040233  PMID: 21359191
14.  Impact of Vacuum-Assisted Closure (VAC) Therapy on Clinical Outcomes of Patients with Sternal Wound Infections: A Meta-Analysis of Non-Randomized Studies 
PLoS ONE  2013;8(5):e64741.
Objective
To examine the impact of VAC therapy on mortality of patients with sternal wound infections after cardiothoracic surgery.
Summary Background Data
Controversial results regarding mortality of patients with sternal wound infections were published.
Methods
We performed a systematic search in PubMed and Scopus. Mortality was the primary outcome of the meta-analysis. Recurrences, complications and length of stay were secondary outcomes.
Results
Twenty-two retrospective studies including 2467 patients were eligible for inclusion. Patients treated with VAC had significantly lower mortality compared to those treated without VAC [2233 patients, RR = 0.40, (95% CI 0.28, 0.57)]. This finding was consistent regardless of the study design, the exclusion of studies with positive findings, the criteria for establishment of the compared groups, the time of mortality assessment or the type of infections under study, provided that adequate data was available. VAC therapy was associated with fewer recurrences (RR = 0.34, 95% CI: 0.19–0.59). The meta-analysis did not show any difference in the length of stay (RR = −2.25, 95% CI: −7.52–3.02).
Conclusions
VAC therapy was associated with lower mortality than other surgical techniques in retrospective cohorts of patients with DSWIs following cardiothoracic surgery.
doi:10.1371/journal.pone.0064741
PMCID: PMC3669405  PMID: 23741379
15.  HIV/AIDS, Comorbidity, and Alcohol 
Alcohol use is common among people infected with HIV and plays an important role in their health outcomes. Because alcohol use complicates HIV infection and contributes to comorbid diseases, it is important for researchers and practitioners to understand these interactions and to integrate alcohol treatment with medical management of long-term HIV infection and associated comorbidity. The Veterans Aging Cohort Study (VACS) is a large, multisite study of the effects of alcohol use on HIV outcomes in the broader context of aging. A multilevel strategy intervention trial is needed to address the many modifiable implications of alcohol consumption among those receiving treatment for HIV.
PMCID: PMC3711181  PMID: 23584067
Alcohol consumption; human immunodeficiency virus; acquired immune deficiency syndrome; comorbidity; disease factor; aging; Veterans Aging Cohort study; treatment method
16.  HIV/AIDS, Comorbidity, and Alcohol 
Alcohol Research & Health  2010;33(3):258-266.
Alcohol use is common among people infected with HIV and plays an important role in their health outcomes. Because alcohol use complicates HIV infection and contributes to comorbid diseases, it is important for researchers and practitioners to understand these interactions and to integrate alcohol treatment with medical management of long-term HIV infection and associated comorbidity. The Veterans Aging Cohort Study (VACS) is a large, multisite study of the effects of alcohol use on HIV outcomes in the broader context of aging. A multilevel strategy intervention trial is needed to address the many modifiable implications of alcohol consumption among those receiving treatment for HIV.
PMCID: PMC3711181  PMID: 23584067
Alcohol consumption; human immunodeficiency virus; acquired immune deficiency syndrome; comorbidity; disease factor; aging; Veterans Aging Cohort study; treatment method
17.  Use of vacuum assisted closure in instrumented spinal deformities for children with postoperative deep infections 
Indian Journal of Orthopaedics  2010;44(2):177-183.
Background:
Postoperative deep infections are relatively common in children with instrumented spinal deformities, whose healing potential is somewhat compromised. Children with underlying diagnosis of cerebral palsy, spina bifida and other chronic debilitating conditions are particularly susceptible. Vacuum-assisted closure (VAC) is a newer technique to promote healing of wounds resistant to treatment by established methods. This article aims to review the efficacy of the VAC system in the treatment of deep spinal infections following spinal instrumentation and fusion in children and adolescents.
Materials and Methods:
We reviewed 33 patients with deep postoperative surgical site infection treated with wound VAC technique. We reviewed clinical and laboratory data, including the ability to retain the spinal hardware, loss of correction and recurrent infections.
Results:
All patients successfully completed their wound VAC treatment regime. None had significant loss of correction and one had persistent infection requiring partial hardware removal. The laboratory indices normalized in all but three patients.
Conclusions:
Wound VAC technique is a useful tool in the armamentarium of the spinal surgeon dealing with patients susceptible to wound infections, especially those with neuromuscular diseases. It allows for retention of the instrumentation and maintenance of the spinal correction. It is reliable and easy to use.
doi:10.4103/0019-5413.62067
PMCID: PMC2856393  PMID: 20419005
VAC therapy; deep wound infection; spinal deformity
18.  Management of upper intestinal leaks using an endoscopic vacuum-assisted closure system (E-VAC) 
Surgical Endoscopy  2013;28:896-901.
Background
Esophageal perforations and postoperative leakage of esophagogastrostomy are considered to be life-threatening conditions due to the development of mediastinitis and consecutive sepsis. Vacuum-assisted closure (VAC), a well-established treatment method for superficial infected wounds, is based on a negative pressure applied to the wound via a vacuum-sealed sponge. Endoluminal VAC (E-VAC) therapy is a novel method, and experience with its esophageal application is limited.
Methods
This retrospective study summarizes the experience of a center with a high volume of upper gastrointestinal surgery using E-VAC therapy for patients with leakages of the esophagus. The study investigated 14 patients who had esophageal defects treated with E-VAC. Three patients had a spontaneous defect; two patients had an iatrogenic defect; and nine patients had a postoperative esophageal defect.
Results
The average duration of application was 12.1 days, and an average of 3.9 E-VAC systems were used. For 6 of the 14 patients, E-VAC therapy was combined with the placement of self-expanding metal stents. Complete restoration of the esophageal defect was achieved in 12 (86 %) of the 14 patients. Two patients died due to prolonged sepsis.
Conclusion
This report demonstrates that E-VAC therapy adds an additional treatment option for partial esophageal wall defects. The combination of E-VAC treatment and endoscopic stenting is a successful novel procedure for achieving a high closure rate.
doi:10.1007/s00464-013-3244-5
PMCID: PMC3931933  PMID: 24149851
Esophageal perforation; Anastomotic leakage; Endoscopic vacuum-assisted closure system
19.  HIV Infection and Risk for Incident Pulmonary Diseases in the Combination Antiretroviral Therapy Era 
Rationale: In aging HIV-infected populations comorbid diseases are important determinants of morbidity and mortality. Pulmonary diseases have not been systematically assessed in the combination antiretroviral therapy (ART) era.
Objectives: To determine the incidence of pulmonary diseases in HIV-infected persons compared with HIV-uninfected persons.
Methods: We analyzed data from the Veterans Aging Cohort Study Virtual Cohort, consisting of 33,420 HIV-infected veterans and 66,840 age, sex, race and ethnicity, and site-matched HIV-uninfected veterans. Using Poisson regression, incidence rates and adjusted incidence rate ratios were calculated to determine the association of HIV with pulmonary disease. The Virtual Cohort was merged with the 1999 Veterans Large Health Survey to adjust for self-reported smoking in a nested sample (14%).
Measurements and Main Results: Incident chronic obstructive pulmonary disease, lung cancer, pulmonary hypertension, and pulmonary fibrosis, as well as pulmonary infections, were significantly more likely among HIV-infected patients compared with uninfected patients in adjusted analyses, although rates of asthma did not differ by HIV status. Bacterial pneumonia and chronic obstructive pulmonary disease were the two most common incident pulmonary diseases, whereas opportunistic pneumonias were less common. Absolute rates of most pulmonary diseases increased with age, although the relative differences between those with and without HIV infection were greatest in younger persons. Chronic obstructive pulmonary disease and asthma, as well as pulmonary infections, were less likely in those with lower HIV RNA levels and use of ART at baseline.
Conclusions: Pulmonary diseases among HIV-infected patients receiving care within the Veterans Affairs Healthcare System in the combination ART era reflect a substantial burden of non–AIDS-defining and chronic conditions, many of which are associated with aging.
doi:10.1164/rccm.201006-0836OC
PMCID: PMC3266024  PMID: 20851926
HIV; respiratory tract diseases; lung diseases, obstructive; pneumonia; pneumonia, bacterial
20.  Evaluation of knowledge levels amongst village AIDS committees after undergoing HIV educational sessions: results from a pilot study in rural Tanzania 
Background
Village AIDS committees (VAC) were formed by the Tanzanian government in 2003 to provide HIV education to their communities. However, their potential has not been realised due to their limited knowledge and misconceptions surrounding HIV, which could be addressed through training of VAC members. In an attempt to increase HIV knowledge levels and address common misconceptions amongst the VACs, an HIV curriculum was delivered to members in rural north western Tanzania.
Methods
An evaluation of HIV knowledge was conducted prior to and post-delivery of HIV training sessions, within members of three VACs in Kisesa ward. Quantitative surveys were used with several open-ended questions to identify local misconceptions and evaluate HIV knowledge levels. Short educational training sessions covering HIV transmission, prevention and treatment were conducted, with each VAC using quizzes, role-plays and participatory learning and action tools. Post-training surveys occurred up to seven days after the final training session.
Results
Before the training, "good" HIV knowledge was higher amongst men than women (p = 0.041), and among those with previous HIV education (p = 0.002). The trade-centre had a faster turn-over of VAC members, and proximity to the trade-centre was associated with a shorter time on the committee.
Training improved HIV knowledge levels with more members achieving a "good" score in the post-training survey compared with the baseline survey (p = < 0.001). The training programme was popular, with 100% of participants requesting further HIV training in the future and 51.7% requesting training at three-monthly intervals.
Conclusions
In this setting, a series of HIV training sessions for VACs demonstrated encouraging results, with increased HIV knowledge levels following short educational sessions. Further work is required to assess the success of VAC members in disseminating this HIV education to their communities, as well as up-scaling this pilot study to other regions in Tanzania with different misconceptions.
doi:10.1186/1472-698X-11-14
PMCID: PMC3262745  PMID: 22165999
21.  The VACS Index Accurately Predicts Mortality and Treatment Response among Multi-Drug Resistant HIV Infected Patients Participating in the Options in Management with Antiretrovirals (OPTIMA) Study 
PLoS ONE  2014;9(3):e92606.
Objectives
The VACS Index is highly predictive of all-cause mortality among HIV infected individuals within the first few years of combination antiretroviral therapy (cART). However, its accuracy among highly treatment experienced individuals and its responsiveness to treatment interventions have yet to be evaluated. We compared the accuracy and responsiveness of the VACS Index with a Restricted Index of age and traditional HIV biomarkers among patients enrolled in the OPTIMA study.
Methods
Using data from 324/339 (96%) patients in OPTIMA, we evaluated associations between indices and mortality using Kaplan-Meier estimates, proportional hazards models, Harrel’s C-statistic and net reclassification improvement (NRI). We also determined the association between study interventions and risk scores over time, and change in score and mortality.
Results
Both the Restricted Index (c = 0.70) and VACS Index (c = 0.74) predicted mortality from baseline, but discrimination was improved with the VACS Index (NRI = 23%). Change in score from baseline to 48 weeks was more strongly associated with survival for the VACS Index than the Restricted Index with respective hazard ratios of 0.26 (95% CI 0.14–0.49) and 0.39(95% CI 0.22–0.70) among the 25% most improved scores, and 2.08 (95% CI 1.27–3.38) and 1.51 (95%CI 0.90–2.53) for the 25% least improved scores.
Conclusions
The VACS Index predicts all-cause mortality more accurately among multi-drug resistant, treatment experienced individuals and is more responsive to changes in risk associated with treatment intervention than an index restricted to age and HIV biomarkers. The VACS Index holds promise as an intermediate outcome for intervention research.
doi:10.1371/journal.pone.0092606
PMCID: PMC3965438  PMID: 24667813
22.  Comparision of Vacuum-Asisted Closure and Moist Wound Dressing in the Treatment of Diabetic Foot Ulcers 
Background:
Vacuum-assisted closure (VAC) is a new method in wound care which speeds wound healing by causing vacuum, improving tissue perfusion and suctioning the exudates. This study aims to evaluate its efficacy in the treatment of diabetic foot ulcers.
Materials and Methods:
Thirteen patients with diabetic foot ulcers were enrolled in the moist dressing group, and 10 patients in the VAC group. The site, size and depth of the wound were inspected and recorded before and every three days during the study period. Patient satisfaction and formation of granulation tissue were also assessed.
Results:
Improvement of the wound in the form of reducing the diameter and depth and increasing proliferation of granulation tissue was significant in most of the patients of the VAC group after two weeks. Satisfaction of patients in the VAC group was evaluated as excellent as no amputation was done in this group. Wagner score was reduced in both the study groups, although this decrement was not significant in the moist dressing group.
Conclusion:
VAC appears to be as safe as and more efficacious than moist dressing for the treatment of diabetic foot ulcers.
doi:10.4103/0974-2077.110091
PMCID: PMC3663170  PMID: 23723599
Diabetic foot ulcers; moist wound dressing; vacuum-assisted closure; wound therapy
23.  Resistance to respiratory syncytial virus (RSV) challenge induced by infection with a vaccinia virus recombinant expressing the RSV M2 protein (Vac-M2) is mediated by CD8+ T cells, while that induced by Vac-F or Vac-G recombinants is mediated by antibodies. 
Journal of Virology  1992;66(2):1277-1281.
It was previously demonstrated that the vaccinia virus recombinants expressing the respiratory syncytial virus (RSV) F, G, or M2 (also designated as 22K) protein (Vac-F, Vac-G, or Vac-M2, respectively) induced almost complete resistance to RSV challenge in BALB/c mice. In the present study, we sought to identify the humoral and/or cellular mediators of this resistance. Mice were immunized by infection with a single recombinant vaccinia virus and were subsequently given a monoclonal antibody directed against CD4+ or CD8+ T cells or gamma interferon (IFN-gamma) to cause depletion of effector T cells or IFN-gamma, respectively, at the time of RSV challenge (10 days after immunization). Mice immunized with Vac-F or Vac-G were completely or almost completely resistant to RSV challenge after depletion of both CD4+ and CD8+ T cells prior to challenge, indicating that these cells were not required at the time of virus challenge for expression of resistance to RSV infection induced by the recombinants. In contrast, the high level of protection of mice immunized with Vac-M2 was completely abrogated by depletion of CD8+ T cells, whereas depletion of CD4+ T cells or IFN-gamma resulted in intermediate levels of resistance. These results demonstrate that antibodies are sufficient to mediate the resistance to RSV induced by the F and G proteins, whereas the resistance induced by the M2 protein is mediated primarily by CD8+ T cells, with CD4+ T cells and IFN-gamma also contributing to resistance.
PMCID: PMC240842  PMID: 1731105
24.  Vincristine, Actinomycin, and Cyclophosphamide Compared With Vincristine, Actinomycin, and Cyclophosphamide Alternating With Vincristine, Topotecan, and Cyclophosphamide for Intermediate-Risk Rhabdomyosarcoma: Children's Oncology Group Study D9803 
Journal of Clinical Oncology  2009;27(31):5182-5188.
Purpose
The purpose of this study was to compare the outcome of patients with intermediate-risk rhabdomyosarcoma (RMS) treated with standard VAC (vincristine, dactinomycin, and cyclophosphamide) chemotherapy to that of patients treated with VAC alternating with vincristine, topotecan, and cyclophosphamide (VAC/VTC).
Patients and Methods
Patients were randomly assigned to 39 weeks of VAC versus VAC/VTC; local therapy began after week 12. Patients with parameningeal RMS with intracranial extension (PME) were treated with VAC and immediate x-ray therapy. The primary study end point was failure-free survival (FFS). The study was designed with 80% power (5% two-sided α level) to detect an increase in 5-year FFS from 64% to 75% with VAC/VTC.
Results
A total of 617 eligible patients were entered onto the study: 264 were randomly assigned to VAC and 252 to VAC/VTC; 101 PME patients were nonrandomly treated with VAC. Treatment strata were embryonal RMS, stage 2/3, group III (33%); embryonal RMS, group IV, less than age 10 years (7%); alveolar RMS or undifferentiated sarcoma (UDS), stage 1 or group I (17%); alveolar RMS/UDS (27%); and PME (16%). At a median follow-up of 4.3 years, 4-year FFS was 73% with VAC and 68% with VAC/VTC (P = .3). There was no difference in effect of VAC versus VAC/VTC across risk groups. The frequency of second malignancies was similar between the two treatment groups.
Conclusion
For intermediate-risk RMS, VAC/VTC does not significantly improve FFS compared with VAC.
doi:10.1200/JCO.2009.22.3768
PMCID: PMC2773476  PMID: 19770373
25.  VacA, the vacuolating cytotoxin of Helicobacter pylori, binds to multimerin 1 on human platelets 
Thrombosis Journal  2013;11:23.
Platelets were activated under the infection with H. pylori in human and mice. We investigated the role of VacA, an exotoxin released by H. pylori in this context. Acid-activated VacA, but not heated VacA, induced platelet CD62P expression. However, VacA reacted with none of the alleged VacA receptors present on platelet membranes. We therefore analyzed VacA associated proteins obtained through VacA affinity chromatography, using MALDI-TOF-MS. Multimerin1 was detected in two consecutive experiments, as the binding protein for VacA. Plasmon resonance confirmed their binding, and dot blot analysis revealed that the peptide sequence AA 321-340 of multimerin 1 is the binding site for VacA. In conclusion, we propose a new interaction between multimerin1 and VacA , which may give another insight into H. pylori-induced platelet activations under H. pylori infection.
doi:10.1186/1477-9560-11-23
PMCID: PMC3842841  PMID: 24219705
Platelet; VacA; Multimerin1; CD62P; ITP

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