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Research Interests: Pulmonology, Medicine, Critical Care, Humans, COPD, and 15 moreNursing Homes, Female, Male, Cohort, Medicare, Clinical Sciences, Aged, Mechanical Ventilation, Retrospective Studies, Intensive Care Medicine, Disease Progression, Hospital Mortality, Exacerbation, Patient readmission, and Respiration Artificial
BackgroundDexamethasone decreases mortality in coronavirus disease 2019 (COVID-19) patients on intensive respiratory support (IRS) but is of uncertain benefit if less severely ill. We determined whether early (within 48 h) dexamethasone... more
BackgroundDexamethasone decreases mortality in coronavirus disease 2019 (COVID-19) patients on intensive respiratory support (IRS) but is of uncertain benefit if less severely ill. We determined whether early (within 48 h) dexamethasone was associated with mortality in patients hospitalised with COVID-19 not on IRS.MethodsWe included patients admitted to US Veterans Affairs hospitals between 7 June 2020 and 31 May 2021 within 14 days after a positive test for severe acute respiratory syndrome coronavirus 2. Exclusions included recent prior corticosteroids and IRS within 48 h. We used inverse probability of treatment weighting (IPTW) to balance exposed and unexposed groups, and Cox proportional hazards models to determine 90-day all-cause mortality.ResultsOf 19 973 total patients (95% men, median age 71 years, 27% black), 15 404 (77%) were without IRS within 48 h. Of these, 3514 out of 9450 (34%) patients on no oxygen received dexamethasone and 1042 (11%) died; 4472 out of 5954 (75%)...
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Objectives: To determine whether early oral or parenteral corticosteroids compared to no corticosteroids are associated with decreased mortality in patients hospitalized with coronavirus disease 2019 (COVID-19) who are not on intensive... more
Objectives: To determine whether early oral or parenteral corticosteroids compared to no corticosteroids are associated with decreased mortality in patients hospitalized with coronavirus disease 2019 (COVID-19) who are not on intensive respiratory support (IRS) within 48 hours of admission. Design: Observational cohort study Setting: Nationwide cohort of patients receiving care in the Department of Veterans Affairs, a large integrated US national healthcare system Participants: 9,058 patients admitted to a Veterans Affairs Medical Center between June 7, 2020-December 5, 2020 within 14-days after SARS-CoV-2 positive test; exclusion criteria include less than a 48 hour stay, receipt of prior systemic corticosteroids, and no indication of acute medical care for COVID-19. Main outcome measure: 90-day all-cause mortality Results: Of 9,058 total patients (95% men, median age 71 years, 27% black), 6,825 (75%) were not on IRS within 48 hours. Among the 3,025 patients on no oxygen, 598 (20%)...
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Background We ascertained incidence of opportunistic infections (OIs) in people with human immunodeficiency virus (PWH) with cancer undergoing chemotherapy with non-human immunodeficiency virus (HIV) comparators. Methods We identified... more
Background We ascertained incidence of opportunistic infections (OIs) in people with human immunodeficiency virus (PWH) with cancer undergoing chemotherapy with non-human immunodeficiency virus (HIV) comparators. Methods We identified 2106 PWH and 2981 uninfected Veterans with cancer who received at least 1 dose of chemotherapy between 1996 and 2017 from the Veterans Aging Cohort Study. We ascertained incident OIs within 6 months of chemotherapy amongst zoster, cytomegalovirus, tuberculosis, Candida esophagitis, Pneumocystis jirovecii pneumonia (PCP), toxoplasmosis, Cryptococcosis, atypical Mycobacterium infection, Salmonella bacteremia, histoplasmosis, coccidioidomycosis, or progressive multifocal leukoencephalopathy. We used Poisson methods to calculate OI incidence rates by HIV status, stratifying for hematological and nonhematological tumors. We compared OI rates by HIV status, using inverse probability weights of HIV status, further adjusting for PCP prophylaxis. Results We con...
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Background Hospitalization with community‐acquired pneumonia (CAP) is associated with an increased risk of cardiovascular disease (CVD) events in patients uninfected with HIV. We evaluated whether people living with HIV (PLWH) have a... more
Background Hospitalization with community‐acquired pneumonia (CAP) is associated with an increased risk of cardiovascular disease (CVD) events in patients uninfected with HIV. We evaluated whether people living with HIV (PLWH) have a higher risk of CVD or mortality than individuals uninfected with HIV following hospitalization with CAP. Methods and Results We analyzed data from the Veterans Aging Cohort Study on US veterans admitted with their first episode of CAP from April 2003 through December 2014. We used Cox regression analyses to determine whether HIV status was associated with incident CVD events and mortality from date of admission through 30 days after discharge (30‐day mortality), adjusting for known CVD risk factors. We included 4384 patients (67% [n=2951] PLWH). PLWH admitted with CAP were younger, had less severe CAP, and had fewer CVD risk factors than patients with CAP who were uninfected with HIV. In multivariable‐adjusted analyses, CVD risk was similar in PLWH comp...
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ImportanceSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes coronavirus disease 2019 (Covid-19), an evolving pandemic. Limited data are available characterizing SARS-Cov-2 infection in the United... more
ImportanceSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes coronavirus disease 2019 (Covid-19), an evolving pandemic. Limited data are available characterizing SARS-Cov-2 infection in the United States.ObjectiveTo determine associations between demographic and clinical factors and testing positive for coronavirus 2019 (Covid-19+), and among Covid-19+ subsequent hospitalization and intensive care.Design, Setting, and ParticipantsRetrospective cohort study including all patients tested for Covid-19 between February 8 and March 30, 2020, inclusive. We extracted electronic health record data from the national Veterans Affairs Healthcare System, the largest integrated healthcare system in the United States, on 2,026,227 patients born between 1945 and 1965 and active in care.ExposuresDemographic data, comorbidities, medication history, substance use, vital signs, and laboratory measures. Laboratory tests were analyzed first individually and then grouped into a...
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Research Interests: Medicine and Lung Cancer
Research Interests: Medicine and Lung Cancer
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Chronic obstructive pulmonary disease (COPD) is a leading cause of death and disability globally. Both cigarette smoking and HIV have been identified as independent risk factors for COPD. We used data from the Strategic Timing of... more
Chronic obstructive pulmonary disease (COPD) is a leading cause of death and disability globally. Both cigarette smoking and HIV have been identified as independent risk factors for COPD. We used data from the Strategic Timing of Antiretroviral Treatment (START) Pulmonary Substudy to quantify the impact of smoking on rate of lung function decline in HIV. We included START Pulmonary Substudy participants who contributed at least two good quality spirometry measures during the study. Slope of forced expiratory volume in 1 second (FEV1) was estimated using a repeated measures model adjusted for treatment group (immediate vs. deferred treatment arm of START), age, sex, race, baseline COPD, and region. Of 1,026 START Pulmonary Substudy participants, 915 (89%) were included in this analysis. Median follow up time was 3.9 years. Smokers and non-smokers were similar in baseline age (median 36 y), but smokers were more likely to be white, male, and from Europe/Israel/Australia. Smokers had f...
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As life expectancy of people living with HIV (PLWH) improves in low-income and middle-income countries (LMICs), the spectrum of HIV-related pulmonary complications may reflect a greater burden of chronic lung diseases as in high-income... more
As life expectancy of people living with HIV (PLWH) improves in low-income and middle-income countries (LMICs), the spectrum of HIV-related pulmonary complications may reflect a greater burden of chronic lung diseases as in high-income countries. We determined whether the risk of abnormal spirometry was greater among adolescent compared with adult PLWH at the Coptic Hope Center for Infectious Diseases in Nairobi, Kenya, and evaluated the role of other cofactors for abnormal spirometry. We prospectively enrolled adolescent and adult PLWH for this cross-sectional study. Data collection included standardized questionnaires, clinical assessment, and prebronchodilator and postbronchodilator spirometry. Adolescents additionally underwent noncontrast chest computed tomography. Multivariable logistic regression determined associations of adolescent age with abnormal spirometry, adjusting for cofactors. Of 427 PLWH, 21 (40%) adolescents and 64 (17%) adults had abnormal spirometry. Among adol...
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No prior studies have addressed the performance of electronic health record (EHR) data to diagnose chronic obstructive pulmonary disease (COPD) in people living with HIV (PLWH), in whom COPD could be more likely to be underdiagnosed or... more
No prior studies have addressed the performance of electronic health record (EHR) data to diagnose chronic obstructive pulmonary disease (COPD) in people living with HIV (PLWH), in whom COPD could be more likely to be underdiagnosed or misdiagnosed, given the higher frequency of respiratory symptoms and smoking compared with HIV-uninfected (uninfected) persons. We determined whether EHR data could improve accuracy of ICD-9 codes to define COPD when compared with spirometry in PLWH vs uninfected, and quantified level of discrimination using the area under the receiver-operating curve (AUC). The development cohort consisted of 350 participants who completed research spirometry in the Examinations of HIV Associated Lung Emphysema (EXHALE) study, a pulmonary substudy of the Veterans Aging Cohort Study. Results were externally validated in 294 PLWH who performed spirometry for clinical indications from the University of Washington (UW) site of the Centers for AIDS Research Network of Int...
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Pneumonia is a complex pulmonary disease in need of new clinical approaches. While triggered by a pathogen, pneumonia often results from dysregulations of host defense that likely precede infection. The coordinated activities of immune... more
Pneumonia is a complex pulmonary disease in need of new clinical approaches. While triggered by a pathogen, pneumonia often results from dysregulations of host defense that likely precede infection. The coordinated activities of immune resistance and tissue resilience then dictate whether and how pneumonia progresses or resolves. Inadequate or inappropriate host responses lead to more severe outcomes such as ARDS and to organ dysfunction beyond the lungs and overextended time-frames after pathogen clearance, some of which increase the risk for subsequent pneumonias. Improved understanding of such host responses will guide the development of novel approaches for preventing and curing pneumonia and for mitigating the subsequent pulmonary and extra-pulmonary complications from pneumonia. The NHLBI assembled a Working Group of extramural investigators to prioritize avenues of host-directed pneumonia research that should yield novel approaches for interrupting the cycle of unhealthy decl...
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With combination-antiretroviral therapy, HIV-infected individuals live longer with an elevated burden of cancer. Given the high prevalence of smoking among HIV-infected populations, we examined the risk of incident cancers attributable to... more
With combination-antiretroviral therapy, HIV-infected individuals live longer with an elevated burden of cancer. Given the high prevalence of smoking among HIV-infected populations, we examined the risk of incident cancers attributable to ever smoking cigarettes. Observational cohort of HIV-infected participants with 270 136 person-years of follow-up in the North American AIDS Cohort Collaboration on Research and Design consortium. Among 52 441 participants, 2306 were diagnosed with cancer during 2000-2015. Estimated hazard ratios and population-attributable fractions (PAF) associated with ever cigarette smoking for all cancers combined, smoking-related cancers, and cancers that were not attributed to smoking. People with cancer were more frequently ever smokers (79%) compared with people without cancer (73%). Adjusting for demographic and clinical factors, cigarette smoking was associated with increased risk of cancer overall [hazard ratios = 1.33 (95% confidence interval: 1.18-1.4...
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Emphysema is one of the most common lung diseases in HIV+ individuals. The pathogenesis of HIV-associated emphysema remains unclear; however, radiographic distribution and earlier age of presentation of emphysema in the lungs of HIV+... more
Emphysema is one of the most common lung diseases in HIV+ individuals. The pathogenesis of HIV-associated emphysema remains unclear; however, radiographic distribution and earlier age of presentation of emphysema in the lungs of HIV+ patients are similar to deficiency of alpha-1 antitrypsin (A1AT), a key elastase inhibitor in the lung. Reduced levels of circulating A1AT have been detected in HIV+ patients, suggesting a potential mechanism for emphysema development. In the present study, we asked if A1AT levels and activity in the bronchoalveolar lavage fluid (BALF) differ in patients with and without HIV and emphysema. A1AT levels were measured by ELISA in plasma and BALF from a cohort of 21 HIV+ and 29 HIV- patients with or without emphysematous changes on chest CT scan. To analyze A1AT function, we measured elastase activity in the BALF and assessed oxidation and polymerization of A1AT by western blotting. Total A1AT was increased in the BALF but not in the plasma of HIV+ compared...
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Patients with heart failure (HF) are at increased risk of unmet palliative care needs. The International Classification of Diseases, Ninth Revision ( ICD-9) code, V66.7, can identify palliative care services. However, code validity for... more
Patients with heart failure (HF) are at increased risk of unmet palliative care needs. The International Classification of Diseases, Ninth Revision ( ICD-9) code, V66.7, can identify palliative care services. However, code validity for specialist palliative care in the Veterans Health Administration (VHA) has not been determined. To validate the ICD-9 code for specialist palliative care and determine common reasons for specialist palliative care consultation among VHA patients hospitalized with HF. Electronic health record review of data from the Veterans Aging Cohort Study. The sample included 100 patients hospitalized with HF from 2003 to 2012. Data from 50 patients with V66.7 were matched by age, race, site of care, hospital length of stay, intensive care unit admission, and fiscal year of study discharge to 50 patients with HF without V66.7 who had died within a year of hospitalization. We calculated positive and negative predictive values (PPV, NPV), sensitivity, and specificit...
Research Interests: Nursing, Emergency Medicine, Gerontology, Palliative Care, Electronic Health Records, and 15 moreMedicine, Heart Failure, Humans, Hospice, Hospitalization, United States, Female, Male, Aged, Middle Aged, International Classification of Diseases, Adult, Veterans Health, Confidence Interval, and Severity of Illness Index
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HIV infection is associated with impaired lung gas transfer as indicated by a low diffusing capacity (DLCO), but the mechanisms are not well understood. We hypothesized that HIV-associated gas exchange impairment is indicative of... more
HIV infection is associated with impaired lung gas transfer as indicated by a low diffusing capacity (DLCO), but the mechanisms are not well understood. We hypothesized that HIV-associated gas exchange impairment is indicative of system-wide perturbations that could be reflected by alterations in peripheral blood leukocyte (PBL) gene expression. Forty HIV-infected (HIV(+)) and uninfected (HIV(-)) men with preserved versus low DLCO were enrolled. All subjects were current smokers and those with acute illness, lung diseases other than COPD or asthma were excluded. Total RNA was extracted from PBLs and hybridized to whole-genome microarrays. Gene set enrichment analysis (GSEA) was performed between HIV(+) versus HIV(-) subjects with preserved DLCO and those with low DLCO to identify differentially activated pathways. Using pathway-based analyses, we found that in subjects with preserved DLCO, HIV infection is associated with activation of processes involved in immunity, cell cycle, and...
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The prevalence of emphysema is higher among HIV-infected (HIV+) individuals compared to HIV-uninfected persons. While greater tobacco use contributes, HIV-related effects on immunity likely confer additional risk. Low peripheral blood... more
The prevalence of emphysema is higher among HIV-infected (HIV+) individuals compared to HIV-uninfected persons. While greater tobacco use contributes, HIV-related effects on immunity likely confer additional risk. Low peripheral blood CD4+ to CD8+ T-lymphocyte (CD4/CD8) ratio may reflect chronic inflammation in HIV and may be a marker of chronic lung disease in this population. Therefore, we sought to determine whether the CD4/CD8 ratio was associated with chronic obstructive pulmonary disease (COPD), particularly the emphysema subtype, in a cohort of HIV+ subjects. We performed a cross-sectional analysis of 190 HIV+ subjects enrolled in the Examinations of HIV Associated Lung Emphysema (EXHALE) study. Subjects underwent baseline laboratory assessments, pulmonary function testing and chest computed tomography (CT) analyzed for emphysema severity and distribution. We determined the association between CD4/CD8 ratio and emphysema, and the association between CD4/CD8 ratio and pulmonar...
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HIV infection is independently associated with risk of lung cancer, but few data exist for the relation between longitudinal measurements of immune function and lung-cancer risk in people living with HIV. We followed up participants with... more
HIV infection is independently associated with risk of lung cancer, but few data exist for the relation between longitudinal measurements of immune function and lung-cancer risk in people living with HIV. We followed up participants with HIV from the Veterans Aging Cohort Study for a minimum of 3 years between Jan 1, 1998, and Dec 31, 2012, and used cancer registry data to identify incident cases of lung cancer. The index date for each patient was the later of the date HIV care began or Jan 1, 1998. We excluded patients with less than 3 years' follow-up, prevalent diagnoses of lung cancer, or incomplete laboratory data. We used Cox regression models to investigate the relation between different time-updated lagged and cumulative exposures (CD4 cell count, CD8 cell count, CD4/CD8 ratio, HIV RNA, and bacterial pneumonia) and risk of lung cancer. Models were adjusted for age, race or ethnicity, smoking, hepatitis C virus infection, alcohol use disorders, drug use disorders, and his...
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Author(s): Rodriguez-Barradas, Maria C; Akgun, Kathleen; Brown, Sheldon; Butt, Adeel; Fine, Michael J; Goetz, Matthew Bidwell; Graber, Christopher; Huang, Laurence; Mcginnis, Kathleen; Rimland, David; Justice, Amy C; Crothers, Kristina
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Chronic lung diseases are increasingly recognized complications of vertically-acquired HIV among adolescents in sub-Saharan Africa and may manifest with hypoxia or tachypnea. We sought to determine the prevalence of and risk factors for... more
Chronic lung diseases are increasingly recognized complications of vertically-acquired HIV among adolescents in sub-Saharan Africa and may manifest with hypoxia or tachypnea. We sought to determine the prevalence of and risk factors for hypoxia and tachypnea among adolescents with vertically-acquired HIV in Nairobi, Kenya. We performed a cross-sectional analysis of 258 adolescents with vertically-acquired HIV who were initiating care at the Coptic Hope Center for Infectious Diseases. Adolescents with documented pneumonia were excluded. Hypoxia was defined as resting oxygen saturation ≤92%, and tachypnea was based on the 99 percentile of age-appropriate respiratory rates. Logistic regression models adjusted for demographics and HIV severity estimated odds ratios (ORs) for risk of hypoxia and tachypnea associated with potential risk factors. Overall, 11% of adolescents had hypoxia and 55% had tachypnea. Advanced HIV (adjusted OR [aOR] 2.41) and low CD4 (aOR 1.74) were associated with ...
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The Second Universal Definition of Myocardial Infarction (MI) divides MIs into different types. Type 1 MIs result spontaneously from instability of atherosclerotic plaque, whereas type 2 MIs occur in the setting of a mismatch between... more
The Second Universal Definition of Myocardial Infarction (MI) divides MIs into different types. Type 1 MIs result spontaneously from instability of atherosclerotic plaque, whereas type 2 MIs occur in the setting of a mismatch between oxygen demand and supply, as with severe hypotension. Type 2 MIs are uncommon in the general population, but their frequency in human immunodeficiency virus (HIV)-infected individuals is unknown. To characterize MIs, including type; identify causes of type 2 MIs; and compare demographic and clinical characteristics among HIV-infected individuals with type 1 vs type 2 MIs. This longitudinal study identified potential MIs among patients with HIV receiving clinical care at 6 US sites from January 1, 1996, to March 1, 2014, using diagnoses and cardiac biomarkers recorded in the centralized data repository. Sites assembled deidentified packets, including physician notes and electrocardiograms, procedures, and clinical laboratory tests. Two physician experts ...
Research Interests: Hematology, Cardiovascular, Electrocardiography, HIV, Clinical research, and 15 moreCholesterol, Female, Diagnosis, Cocaine, Homo Sapiens, Hiv Infection, Heart Disease, Human immunodeficiency virus, Cells, Coronary Angiography, Adult, Bacteremia, Biological markers, HIV infections, and Coronary Artery Bypass
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Research Interests: Pediatrics, Adolescent, Medicine, Linear models, Multivariate Analysis, and 15 moreProspective studies, Humans, Female, Male, Lung, Aged, Middle Aged, Adult, Quinolines, Azithromycin, Bronchiolitis Obliterans, Hematopoietic Stem Cell Transplantation, Postoperative Complications, Pulmonary function testing, and Fluticasone
Chronic obstructive pulmonary disease (COPD) prevalence is increasing among aging HIV-infected individuals. We determined the association between COPD and self-reported measures of frailty (adapted frailty-related phenotype (aFRP)) and... more
Chronic obstructive pulmonary disease (COPD) prevalence is increasing among aging HIV-infected individuals. We determined the association between COPD and self-reported measures of frailty (adapted frailty-related phenotype (aFRP)) and physical limitation (PL), and a clinical biomarker of physiologic frailty (VACS Index) in HIV-infected compared with uninfected individuals. Cross-sectional study of Veterans Aging Cohort Study (VACS) participants between 2002-2012. Pre-frail/aFRP was obtained from self-reported surveys. Pre-frail was defined as 1-2 domains of physical shrinking, exhaustion, slowness and low physical activity; aFRP was defined as ≥3 domains. PL scale was determined from 12 self-reported survey items assessing limitations performing physical activities. VACS Index includes age and laboratory measurements. We used regression models to test for associations between COPD and outcomes in models stratified by HIV status. The sample included 3538 HIV-infected and 3606 uninfe...
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Utilizing the Veterans Aging Cohort Study, the largest HIV cohort in North America, we conducted one of the few comprehensive comparisons of cancer incidence time trends in HIV-infected (HIV+) versus uninfected persons during the... more
Utilizing the Veterans Aging Cohort Study, the largest HIV cohort in North America, we conducted one of the few comprehensive comparisons of cancer incidence time trends in HIV-infected (HIV+) versus uninfected persons during the antiretroviral therapy (ART) era. Prospective cohort study. We followed 44,787 HIV+ and 96,852 demographically-matched uninfected persons during 1997-2012. We calculated age-, sex-, and race/ethnicity-standardized incidence rates (IR) and incidence rate ratios (IRR, HIV+ versus uninfected) over four calendar periods with IR and IRR period trend p-values for cancer groupings and specific cancer types. We observed 3,714 incident cancer diagnoses in HIV+ and 5,760 in uninfected persons. The HIV+ all cancer crude IR increased between 1997-2000 and 2009-2012 (p-trend = 0.0019). However, after standardization, we observed highly significant HIV+ IR declines for all cancer (25% decline; p-trend<0.0001), AIDS-defining cancers (ADC; 55% decline; p-trend<0.0001...
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Previous work found the lung microbiome in healthy HIV-infected subjects was similar to uninfected subjects. We hypothesized lung microbiome from HIV-infected subjects with more advanced disease would differ from an uninfected control... more
Previous work found the lung microbiome in healthy HIV-infected subjects was similar to uninfected subjects. We hypothesized lung microbiome from HIV-infected subjects with more advanced disease would differ from an uninfected control population. To measure the lung microbiome in an HIV-infected population with advanced disease. 16s RNA gene sequencing was performed on acellular bronchoalveolar lavage (BAL) fluid from 30 HIV-infected subjects with advanced disease (baseline mean CD4 count 262 cells/mm3) before and up to three years after starting highly active antiretroviral therapy (HAART) and compared to 22 uninfected controls. The lung microbiome HIV-infected subjects with advanced disease demonstrated decreased alpha diversity (richness and diversity) and greater beta diversity compared to uninfected BAL. Differences improved with HAART, but still persisted up to three years after starting therapy. Population dispersion in the HIV-infected group was significantly greater than in...
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Research Interests: Medicine, Biological Sciences, Humans, COPD, Internal Medicine, and 15 moreAlcoholism, Female, Male, AIDS, Incidence, Middle Aged, Longitudinal Studies, Adult, Chronic obstructive pulmonary disease, Disease Progression, Psychology and Cognitive Sciences, Exacerbation, Medical and Health Sciences, HIV infections, and Pulmonary Disease Chronic Obstructive
Research Interests: Epidemiology, Immunology, Biostatistics, Life Sciences, Medicine, and 15 moreProspective studies, Humans, Female, Male, Lung, Middle Aged, Microbiome, Adult, Mouth, Highly Active Antiretroviral Therapy, Microbiota, Medicine and Health Sciences, Cohort Studies, Medical and Health Sciences, and HIV infections
Background: Although community–acquired pneumonia (CAP) is a leading cause of death in HIV-uninfected older adults, health outcomes among HIV-infected older adults are not well defined. Methods: Associations between HIV infection and... more
Background: Although community–acquired pneumonia (CAP) is a leading cause of death in HIV-uninfected older adults, health outcomes among HIV-infected older adults are not well defined. Methods: Associations between HIV infection and three health outcomes (30-day mortality, hospital readmission within 30 days post-discharge, and hospital length of stay [LOS]) were examined using data from the Veterans Aging Cohort Study Virtual Cohort of male Veterans age ≥50 hospitalized for CAP from 10/1/2002 to 08/31/2010. The association between age and HIV status (using CD4 cell count, viral load, or use of antiretroviral therapy [ART]) and 30-day mortality was assessed with Cox regression. Hospital readmission within 30 days post-discharge was analyzed by logistic regression and LOS by linear regression. All models adjusted for race, smoking status, pulmonary co-morbidity, alcohol and substance abuse. Results: Among the cohort of 117,557 Veterans (80,635 HIV-uninfected and 36,922 HIV-infected ...
Background: HIV infected subjects (HIV+) have a high incidence of pneumococcal disease and vaccination is recommended, but its effectiveness is not established. We evaluated the effect of PV on hospitalization rates for non-PCP pneumonia... more
Background: HIV infected subjects (HIV+) have a high incidence of pneumococcal disease and vaccination is recommended, but its effectiveness is not established. We evaluated the effect of PV on hospitalization rates for non-PCP pneumonia among HIV+ compared to uninfected patients (HIV-) enrolled in the Veterans Aging Cohort 5-site Study. Methods: 700 HIV- and 969 HIV+ participated. Index date was PV date (within 3 y pre- or 2 y post-enrollment) for vaccinated subjects (PV+) and enrollment date for unvaccinated subjects (PV-). The primary outcome was an event of hospitalization for non-PCP pneumonia (Pn). Using survival analysis we determined the hazard ratio (HR) for pneumonia, controlling for age, ethnicity, tobacco use, alcohol disorders, drug use, COPD, prior pneumonia, and among HIV+, CD4 and viral load. Results: HIV- HIV+ PV- PV+ PV- PV+ N (%) 373 (53) 327 (47) 294 (30) 675 (70) Median age 53 y 57 y 49 y 50 y Pn events [n (%)] 5 (1.3) 8 (2.4) 35 (12.0) 56 (8.0) <6 m 1 (0.3) ...
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PURPOSE/AIM Illustrate HIV-related thoracic diseases in the modern era of HAART with radiographic and CT images Elucidate disease pathophysiology with pathologic and clinical correlations CONTENT ORGANIZATION 1. Introduction – Recent... more
PURPOSE/AIM Illustrate HIV-related thoracic diseases in the modern era of HAART with radiographic and CT images Elucidate disease pathophysiology with pathologic and clinical correlations CONTENT ORGANIZATION 1. Introduction – Recent progress and statistics of HIV and HAART 2. HIV-related thoracic diseases – Imaging findings and pathologic correlations a. Immune reconstitution inflammatory syndrome (IRIS) IRIS in the setting of TB, Non-TB mycobacteria, pneumocystis, etc. IRIS in the absence of known residual antigenic load b. COPD / Emphysema in HIV c. Pulmonary hypertension d. Primary lung cancer e. Drug-induced pulmonary diseases and toxicity Diffuse interstitial lung disease, focal consolidations Hypersensitivity reaction, bacterial pneumonia f. Non-infectious pulmonary complications NSIP LIP Lymphoma 3. TB Drug sensitive TB Drug resistant TB Multi-drug resistant TB (MDR-TB) Extremely drug resistant TB (XDR-TB) 4. Conclusion SUMMARY In the modern era, IRIS, COPD, and lung cancer ...
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As antiretroviral treatments prolong life in HIV-infected patients, smoking cessation is now a top priority. However, studies of HIV-infected smokers have not been conducted with uninfected controls. We determined factors associated with... more
As antiretroviral treatments prolong life in HIV-infected patients, smoking cessation is now a top priority. However, studies of HIV-infected smokers have not been conducted with uninfected controls. We determined factors associated with contemplating smoking cessation and making a prior quit attempt among HIV-infected and uninfected smoking Veterans. Between 2005 and 2007, we identified 1027 HIV-infected and 794 uninfected smokers enrolled in the Veterans Aging Cohort Study (VACS). Stratifying by HIV status, we calculated adjusted odd ratios using logistic regression to identify factors associated with contemplating smoking cessation and making a prior quit attempt. Most participants (66% of HIV-infected vs. 68% of uninfected, p=0.46) were contemplating cessation, and 56% of both groups (p=0.99) had attempted to quit in the last year. In stratified multivariable analyses, HIV-infected smokers with recent pulmonary disease diagnoses were more likely to have made a quit attempt (AOR 4.93, 95% CI=1.41-17.17). Both HIV-infected and uninfected patients with unhealthy alcohol use were less likely to be contemplating cessation (AOR 0.66, 95% CI=0.49-0.90 and 0.71, 95% CI=0.50-1.00). HIV-infected smokers who reported unhealthy alcohol use were also less likely to have made a quit attempt in the last year (AOR 0.68, 95% CI=0.51-0.91). Patient-level interest and motivation are not major barriers to smoking cessation among HIV-infected Veterans. Targeting HIV-infected smokers with a recent pulmonary disease diagnosis may improve sustained smoking cessation. Unhealthy alcohol use appears to be a key modifiable risk factor. Smoking cessation rates may be improved by combining interventions for smoking and alcohol use for HIV-infected patients.
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Research Interests: Medicine and Tuberculosis
Pulmonary diseases are major causes of morbidity and death in persons with HIV infection. Millions of people with HIV/AIDS throughout the world are at risk of opportunistic pneumonias such as tuberculosis, bacterial pneumonia, and... more
Pulmonary diseases are major causes of morbidity and death in persons with HIV infection. Millions of people with HIV/AIDS throughout the world are at risk of opportunistic pneumonias such as tuberculosis, bacterial pneumonia, and Pneumocystis pneumonia. However, the availability of combination antiretroviral therapy has turned HIV into a chronic disease, and noninfectious lung diseases such as lung cancer, chronic obstructive pulmonary disease, and pulmonary arterial hypertension are also emerging as important causes of illness. Despite the importance of these diseases and the rapidly evolving understanding of their pathogenesis and epidemiology, few avenues exist for the discussion and dissemination of new clinical and basic insights. In May of 2008, the American Thoracic Society sponsored a 1-day workshop, "Emerging Issues and Current Controversies in HIV-Associated Pulmonary Diseases," which brought together basic and clinical researchers in HIV-associated pulmonary di...
Research Interests: Risk assessment, Medicine, Comorbidity, Tuberculosis, Humans, and 14 moreUnited States, Female, Disease, Pneumonia, Male, Incidence, Anti-Bacterial Agents, Survival Rate, Prognosis, Intensive Care Medicine, Risk Assessment, Pulmonary Tuberculosis, Severity of Illness Index, and Pneumocystis pneumonia
Smoking-related diseases, such as chronic obstructive pulmonary disease (COPD), are of particular concern in the HIV-infected population. Smoking rates are high in this population, and long-term exposure to cigarette smoke in the setting... more
Smoking-related diseases, such as chronic obstructive pulmonary disease (COPD), are of particular concern in the HIV-infected population. Smoking rates are high in this population, and long-term exposure to cigarette smoke in the setting of HIV infection may increase the number of complications seen. Before the era of combination antiretroviral therapy, HIV-infected persons were noted to have an accelerated form of COPD, with significant emphysematous disease seen in individuals less than 40 years old. Unlike many of the AIDS-defining opportunistic infections, HIV-associated COPD may be more common in the current era of HIV because it is frequently reported in patients without a history of AIDS-related pulmonary complications and because many aging HIV-infected individuals have had a longer exposure to smoking and HIV. In this review, we document the epidemiology of HIV-associated COPD before and after the institution of combination antiretroviral therapy, review data suggesting tha...
Research Interests: Health Behavior, Epidemiology, Immunology, Inflammation, Autoimmunity, and 15 moreOxidative Stress, Macrophages, Apoptosis, Medicine, Population, Humans, COPD, Endothelial Cells, Animals, Lung, Epithelial cells, Airway Obstruction, Respiratory function tests, HIV infections, and Pulmonary Disease Chronic Obstructive
In HIV-uninfected populations, obstructive sleep apnoea (OSA) is commonly associated with cardiovascular disease, metabolic syndrome, and cognitive impairment. These comorbidities are common in HIV-infected patients, but there are scarce... more
In HIV-uninfected populations, obstructive sleep apnoea (OSA) is commonly associated with cardiovascular disease, metabolic syndrome, and cognitive impairment. These comorbidities are common in HIV-infected patients, but there are scarce data regarding OSA in HIV-infected patients. Therefore, we examined the prevalence and correlates of OSA in a cohort of HIV-infected and uninfected patients. An observational cohort study was carried out. Electronic medical record and self-report data were examined in patients enrolled in the Veterans Aging Cohort Study (VACS) between 2002 and 2008 and followed until 2010. The primary outcome was OSA diagnosis, determined using International Classification of Diseases, 9th edition (ICD-9) codes, in HIV-infected compared with uninfected individuals. We used regression analyses to determine the association between OSA diagnosis, symptoms and comorbidities in adjusted models. Of 3683 HIV-infected and 3641 uninfected patients, 143 (3.9%) and 453 (12.4%)...
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Aim: Advance directives are often under-informed due to a lack of disease-specific prognostic information. Without well-informed advance directives patients may receive default care that is incongruent with their preferences. We aimed to... more
Aim: Advance directives are often under-informed due to a lack of disease-specific prognostic information. Without well-informed advance directives patients may receive default care that is incongruent with their preferences. We aimed to further inform advance care planning in patients with severe chronic obstructive pulmonary disease by estimating outcomes with alternative advance directives. Methods: We designed a Markov microsimulation model estimating outcomes for patients choosing between the Full Code advance directive (permitting invasive mechanical ventilation), and the Do Not Intubate directive (only permitting noninvasive ventilation). Results: Our model estimates Full Code patients have marginally increased one-year survival after admission for severe respiratory failure, but are more likely to be residing in a nursing home and have frequent rehospitalizations for respiratory failure. Conclusion: Patients with severe chronic obstructive pulmonary disease may consider thes...
Research Interests: Decision Making, Medicine, Humans, Markov chains, Institutionalisation, and 12 moreComparative Effectiveness, Advance Directives, Mechanical Ventilation, Intensive Care Medicine, Patient Centered Care, Statistical models, Advance Care Planning, Terminal care, Directive, Choice Behavior, Pulmonary Disease Chronic Obstructive, and Respiration Artificial
Alveolar destruction is a cardinal feature of emphysema but is not traditionally believed to contribute to the pathogenesis of "classical" asthma. However, the relationship between chronic obstructive pulmonary disease (COPD)... more
Alveolar destruction is a cardinal feature of emphysema but is not traditionally believed to contribute to the pathogenesis of "classical" asthma. However, the relationship between chronic obstructive pulmonary disease (COPD) and asthma is controversial and the variety of mechanisms that can mediate the alveolar destruction in emphysema have not been adequately defined. To address these issues, we used overexpression transgenic approaches to define the effects of Th1/Tc1 and Th2/Tc2 cytokines in the mature murine lung and compared findings in these transgenic systems to the effects of similar interventions after cigarette smoke (CS) exposure. In these experiments, the Th1/Tc1 and Th2/Tc2 cytokines IFN-gamma and interleukin (IL)-13, respectively, both caused emphysema. The IFN-gamma response was associated with neutrophilia but was not associated with mucus metaplasia or a major fibrotic response. In this setting, IFN-gamma was a potent stimulator of matrix metalloproteinas...
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Patients with respiratory distress often seek emergency medical care and are transported by emergency medical services (EMS). EMS encounters with patients in respiratory distress have not been well described. The study objective was to... more
Patients with respiratory distress often seek emergency medical care and are transported by emergency medical services (EMS). EMS encounters with patients in respiratory distress have not been well described. The study objective was to characterize the epidemiology of prehospital respiratory distress and subsequent patient outcomes. This was a population-based cohort study of noninjured adults transported by EMS to any of 16 hospitals between 2002 and 2006. EMS records were linked to hospital administrative data for encounters categorized by EMS personnel as primarily "respiratory distress" in nature. The authors described prehospital patient and encounter characteristics, interventions, hospital discharge diagnoses (using ICD-9-CM codes), and patient outcomes. The association between prehospital variables, defined a priori, and hospital admission were described using multivariable logistic regression. There were 166,908 EMS encounters, of which 19,858 were for respiratory...
Research Interests: Emergency Medicine, Epidemiology, Medicine, Heart Failure, Emergency Medical Services, and 15 moreHumans, Female, Male, Dyspnea, Clinical Sciences, Washington, Aged, Middle Aged, Retrospective Studies, Intensive Care Units, Logistic Models, Respiratory distress, Respiratory insufficiency, Pulmonary Disease Chronic Obstructive, and Respiration Artificial
The spectrum of lung diseases associated with HIV is broad, and many infectious and noninfectious complications of HIV infection have been recognized. The nature and prevalence of lung complications have not been fully characterized since... more
The spectrum of lung diseases associated with HIV is broad, and many infectious and noninfectious complications of HIV infection have been recognized. The nature and prevalence of lung complications have not been fully characterized since the Pulmonary Complications of HIV Infection Study more than 15 years ago, before antiretroviral therapy (ART) increased life expectancy. Our understanding of the global epidemiology of these diseases in the current ART era is limited, and the mechanisms for the increases in the noninfectious conditions, in particular, are not well understood. The Longitudinal Studies of HIV-Associated Lung Infections and Complications (Lung HIV) Study (ClinicalTrials.gov number NCT00933595) is a collaborative multi-R01 consortium of research projects established by the National Heart, Lung, and Blood Institute to examine a diverse range of infectious and noninfectious pulmonary diseases in HIV-infected persons. This article reviews our current state of knowledge o...
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... University of Washington, Seattle, WA, University of Maryland School of Medicine, Baltimore, Emory University, Atlanta, VA Greater 1 2 3 4 Los Angeles Healthcare Center, Los Angeles, CA, Mount Sinai School of Medicine, New York, David... more
... University of Washington, Seattle, WA, University of Maryland School of Medicine, Baltimore, Emory University, Atlanta, VA Greater 1 2 3 4 Los Angeles Healthcare Center, Los Angeles, CA, Mount Sinai School of Medicine, New York, David Geffen School of Medicine, Los 5 6 ...
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The human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) pandemic has entered its 4th decade. Since the introduction of combination antiretroviral therapy (ART) in 1996, the number of AIDS-related deaths has... more
The human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) pandemic has entered its 4th decade. Since the introduction of combination antiretroviral therapy (ART) in 1996, the number of AIDS-related deaths has plateaued worldwide. Today, owing to the effectiveness of ART, the HIV-infected population is aging and HIV infection has become a chronic illness. Non-AIDS comorbidities are increasing, and the spectrum of HIV-related thoracic diseases is evolving. In developed countries, bacterial pneumonia has become more common than Pneumocystis pneumonia. Its imaging appearance depends on the responsible organism, most commonly Streptococcus pneumoniae. Mycobacterium tuberculosis continues to be a major threat. Its imaging patterns vary depending on CD4 count. Primary lung cancer and Hodgkin lymphoma are two important non-AIDS-defining malignancies that are increasingly encountered at chest imaging. Human herpesvirus 8, also known as Kaposi sarcoma-associated her...
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Research Interests: Decision Making, Survival Analysis, Medicine, Applied Economics, Humans, and 15 moreCOPD, Markov chains, Patient Preference, Life Expectancy, Health Status, Aged, Middle Aged, Quality adjusted life years, Mechanical Ventilation, Patient Participation, Advance Care Planning, Severity of Illness Index, Decision Support Techniques, Exacerbation, and Pulmonary Disease Chronic Obstructive
In the absence of a culture system for clinical isolation of human Pneumocystis, P. jirovecii, the diagnosis of Pneumocystis pneumonia (PcP) relies on the microscopic visualization of characteristic cysts and/or trophic forms in stained... more
In the absence of a culture system for clinical isolation of human Pneumocystis, P. jirovecii, the diagnosis of Pneumocystis pneumonia (PcP) relies on the microscopic visualization of characteristic cysts and/or trophic forms in stained respiratory specimens. Bronchoscopy with ...
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Molecular studies have provided important insights into Pneumocystis and Pneumocystis pneumonia (PcP) [9,12]. In the absence of an in vitro diagnostic culture system, molecular techniques have been used to examine whether human... more
Molecular studies have provided important insights into Pneumocystis and Pneumocystis pneumonia (PcP) [9,12]. In the absence of an in vitro diagnostic culture system, molecular techniques have been used to examine whether human Pneumocystis, P. jirovecii, develops clinical ...
Research Interests: Microbiology, Gerontology, Population Genetics, Biology, Medicine, and 15 moreHumans, Mutation, Parasite, Hiv Infection, The, Genotype, Retrospective Studies, Antifungal Agents, Eukaryotic microbiology, Pneumocystis, Thallophyta, Opportunist, dihydropteroate synthase, Pneumocystis pneumonia, and Pneumocystis carinii
... LAURENCE HUANG, KRISTINA CROTHERS, ALISON MORRIS, GENA GRONER, MELISSA FOX, JOAN R. TURNER, CYNTHIA MERRIFIELD, SHARY EISER, PATRIZIA ZUCCHI, and CHARLES B. BEARD. ... PubMed, CSA. Probst, M., H. Ries, T. Schmidt-Wieland, and A. Serr.... more
... LAURENCE HUANG, KRISTINA CROTHERS, ALISON MORRIS, GENA GRONER, MELISSA FOX, JOAN R. TURNER, CYNTHIA MERRIFIELD, SHARY EISER, PATRIZIA ZUCCHI, and CHARLES B. BEARD. ... PubMed, CSA. Probst, M., H. Ries, T. Schmidt-Wieland, and A. Serr. ...
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Immune reconstitution inflammatory syndrome (IRIS) describes a paradoxical worsening of clinical status related to recovery of the immune system, as can occur after the initiation of highly active antiretroviral therapy (HAART) in... more
Immune reconstitution inflammatory syndrome (IRIS) describes a paradoxical worsening of clinical status related to recovery of the immune system, as can occur after the initiation of highly active antiretroviral therapy (HAART) in HIV-infected patients. Most commonly, IRIS results from opportunistic infections that can unmask or develop paradoxical worsening following HAART. Cancers, autoimmune conditions and sarcoidosis have also been associated with IRIS. Pulmonary complications may be frequently encountered. This article reviews the types and clinical presentation of IRIS, with a focus on the pulmonary manifestations. Management and outcome of IRIS are considered.
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With the introduction of highly active antiretroviral therapy (HAART), HIV has become a chronic disease. As HIV-infected patients are aging, they are at increased risk for comorbid diseases. These non-AIDS related diseases account for a... more
With the introduction of highly active antiretroviral therapy (HAART), HIV has become a chronic disease. As HIV-infected patients are aging, they are at increased risk for comorbid diseases. These non-AIDS related diseases account for a growing proportion of intensive care unit (ICU) admissions in HIV-infected patients in recent studies. HIV-infected patients still present to the ICU with HIV-related conditions such as Pneumocystis jirovecii pneumonia (PCP), but these conditions are becoming less common. Respiratory failure remains the most common indication for ICU admission. Immune reconstitution inflammatory response syndrome and toxicities related to HAART may also result in ICU admission. While ICU survival has improved since the earliest era of the HIV epidemic, hospital mortality for HIV-infected patients admitted to the ICU remains around 30%. Risk factors for ICU mortality include poor functional status, weight loss, more than one year between HIV diagnosis and ICU admissio...
Research Interests: Epidemiology, Aging, Medicine, Humans, INTENSIVE CARE, and 15 moreChronic Disease, Hiv Infection, Incidence, Clinical Sciences, Intensive Care Unit, Human immunodeficiency virus, Mechanical Ventilation, Highly Active Antiretroviral Therapy, Intensive Care Medicine, Intensive Care Units, Hospital Mortality, Functional Status, Critical Illness, Inflammatory response, and HIV infections
Research Interests: Biology, Infectious Diseases, Medicine, Biological Sciences, Prospective studies, and 14 moreHumans, Pneumonia, Polymerase Chain Reaction, Hiv Infection, Infectious, Human immunodeficiency virus, Mouth, Reproducibility of Results, Sensitivity and Specificity, Pneumocystis, Therapeutic Irrigation, Pneumocystis pneumonia, Medical and Health Sciences, and HIV infections
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Research Interests: Epidemiology, Asthma, Medicine, Humans, Female, and 15 morePneumonia, Male, Lung Diseases, Etiology, Incidence, Clinical Sciences, Aged, Prevalence, Chronic obstructive pulmonary disease, Intensive Care Medicine, Idiopathic Pulmonary Fibrosis, Antineoplastic Agents, Adenocarcinoma, lung neoplasms, and Pulmonary Disease Chronic Obstructive
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Research Interests: Medicine, Humans, COPD, Internal Medicine, Male, and 15 moreDyspnea, Dlco, Clinical Sciences, Prevalence, Middle Aged, Longitudinal Studies, Hiv Aids, Age Factors, Cross Sectional Studies, Cough, Pulmonary disease, Pulmonary diffusing capacity, Gas Exchange, HIV infections, and Pulmonary Disease Chronic Obstructive
Although several studies have reported that it is safe to discontinue secondary Pneumocystis carinii pneumonia (PCP) prophylaxis in patients infected with HIV who experience a sustained immune response as a result of antiretroviral... more
Although several studies have reported that it is safe to discontinue secondary Pneumocystis carinii pneumonia (PCP) prophylaxis in patients infected with HIV who experience a sustained immune response as a result of antiretroviral therapy, we describe a patient who developed recurrent PCP &lt;3 months after discontinuing trimethoprim-sulfamethoxazole prophylaxis. He developed disease despite a sustained CD4 T-cell count above 200 cells/microL for more than 3 years while on antiretroviral therapy, as well as an apparent immune reconstitution against disseminated Mycobacterium avium complex (MAC) and Histoplasma capsulatum, for which he also discontinued therapy but without adverse effects. Thus, although increasing evidence continues to indicate that HIV-infected patients receiving combinations of antiretroviral therapies may regain specific immunity against opportunistic infections, our patient&#39;s experience suggests that this immune recovery may be selective and incomplete.
Research Interests: Immunology, HIV medicine, Treatment Outcome, Medicine, Antiretroviral Therapy, and 15 moreHumans, Pneumonia, Male, Hiv Infection, Clinical Sciences, Immune system, Adult, Immune Reconstitution, SECONDARY PREVENTION, opportunistic infection, Adverse effect, Pneumocystis carinii pneumonia, immune reconstitution inflammatory syndrome, Pneumocystis pneumonia, and Pneumocystis carinii
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Research Interests: Microbiology, Medical Microbiology, Biology, Medicine, Gene expression, and 15 moreEmerging Infectious Diseases, Humans, Perspective, Mutation, Drug Resistance, Clinical Sciences, Immunocompromised host, Fungal, Pneumocystis, Bronchoalveolar lavage, Pneumocystis jirovecii, Dapsone, dihydropteroate synthase, Pneumocystis pneumonia, and Pneumocystis carinii
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Research Interests: Microbiology, Immunology, Medical Microbiology, Biology, Medicine, and 15 moreEmerging Infectious Diseases, Antibodies, Humans, Female, Male, Hiv Infection, Clinical Sciences, Middle Aged, Antibody, Adult, Enzyme Linked Immunosorbent Assay, Fungal, Antibody Response, Geometric mean, and HIV infections
Pneumocystis pneumonia (PCP), caused by infection with Pneumocystis jirovecii, remains an important opportunistic infection in humans. A reverse transcriptase polymerase chain reaction assay has been shown to specifically detect viable P.... more
Pneumocystis pneumonia (PCP), caused by infection with Pneumocystis jirovecii, remains an important opportunistic infection in humans. A reverse transcriptase polymerase chain reaction assay has been shown to specifically detect viable P. jirovecii organisms. In the current study, we evaluated this assay on different types of respiratory samples. The assay had a diagnostic sensitivity of 100% and a specificity of 86% when applied to bronchoalveolar lavage samples. The assay&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s performance declined when applied to less invasive induced sputum and oropharyngeal wash (OPW) samples. The sensitivity, when applied to OPWs, was improved by examining multiple sequential OPW samples and was affected by clinical sampling parameters that could increase or decrease the number of potential organisms in the oropharynx. When used in conjunction with an optimized clinical sampling protocol, this assay may become a useful tool for detecting and monitoring P. jirovecii in minimally invasive clinical samples.
Research Interests: Microbiology, Medical Microbiology, Biology, Medicine, HIV, and 15 moreHumans, Infectious Disease, Female, Male, Hiv Infection, Clinical Sciences, Middle Aged, Adult, Minimally Invasive, Bronchoalveolar lavage, Pneumocystis jirovecii, opportunistic infection, HIV infections, Pneumocystis carinii, and Oropharynx
Chronic lung diseases, including chronic obstructive pulmonary disease (COPD) and pulmonary hypertension (PH), are unusually prevalent among persons infected with human immunodeficiency virus (HIV). Often these disease states are... more
Chronic lung diseases, including chronic obstructive pulmonary disease (COPD) and pulmonary hypertension (PH), are unusually prevalent among persons infected with human immunodeficiency virus (HIV). Often these disease states are identified at younger ages than would be expected in the general population. Recent epidemiologic, basic scientific, and cross-sectional clinical data have implicated immune dysfunction and cellular senescence as potential drivers of advanced presentations of age-related diseases in HIV-infected persons. This article describes how HIV-associated COPD and PH may fit into a paradigm of immunosenescence, and outlines the hypothesized associations among chronic HIV infection, immune dysfunction and senescence, and cardiopulmonary outcomes.
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Research Interests: Algorithms, Medicine, Comorbidity, Heart Failure, Humans, and 15 moreCOPD, Internal Medicine, Hypertension, Female, Male, Clinical Sciences, Aged, Middle Aged, Chest, Angiotensin Converting Enzyme Inhibitors, Calcium Channel Blocker, Cohort Studies, Calcium Channel Blockers, Antihypertensive agents, and Pulmonary Disease Chronic Obstructive
... Of note, this decrease in SMA Em is not seen following off-pump cardiac surgery. ... Measurement of SMA Em velocity is not recommended for routine assessment of diastolic function after CPB. This parameter may, however, retain its... more
... Of note, this decrease in SMA Em is not seen following off-pump cardiac surgery. ... Measurement of SMA Em velocity is not recommended for routine assessment of diastolic function after CPB. This parameter may, however, retain its clinical utility after off-pump cardiac surgery. ...
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Research Interests: Information Systems, Computer Science, Medicine, Decision Trees, Humans, and 15 moreCOPD, Clinical Decision Support, Patient Preference, Geomatic Engineering, Decision Tree, Life Expectancy, Clinical Sciences, Advance directive, Advance Directives, Mechanical Ventilation, Chronic obstructive pulmonary disease, Decision Models, Life Quality, Directive, and Decision Support Techniques
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Research Interests: Research Design, English language, Tobacco, Medicine, Lung Cancer, and 15 moreHumans, Generalizability Theory, Selection Criteria, Hyperplasia, Risk factors, Lung, Risk Factors, English Language, Tobacco Smoke, Observational Study, Health Outcome, Alveolar Macrophage, Medical and Health Sciences, lung neoplasms, and Small Sample Size
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The lung is an important reservoir of human immunodeficiency virus (HIV). Individuals infected with HIV are more prone to pulmonary infections and chronic lung disorders. We hypothesized that comprehensively profiling the proteomic... more
The lung is an important reservoir of human immunodeficiency virus (HIV). Individuals infected with HIV are more prone to pulmonary infections and chronic lung disorders. We hypothesized that comprehensively profiling the proteomic landscape of bronchoalveolar lavage fluid (BALF) in patients with HIV would provide insights into how this virus alters the lung milieu and contributes to pathogenesis of HIV-related lung diseases. BALF was obtained from five HIV-negative (HIV−) and six asymptomatic HIV-positive (HIV+) subjects not on antiretroviral therapy. Each sample underwent shotgun proteomic analysis based on HPLC-tandem mass spectrometry. Differentially expressed proteins between the groups were identified using statistical methods based on spectral counting. Mechanisms of disease were explored using functional annotation to identify overlapping and distinct pathways enriched between the BALF proteome of HIV+ and HIV− subjects. We identified a total of 318 unique proteins in BALF o...
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Research Interests: Medicine, HIV, Biological Sciences, Humans, Internal Medicine, and 15 moreMutation, Female, Male, AIDS, Middle Aged, Genotype, Adult, Odds ratio, Logistic Models, Pneumocystis jirovecii, dihydropteroate synthase, Pneumocystis pneumonia, Medical and Health Sciences, HIV infections, and Pneumocystis carinii
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A validated, scalable approach to characterizing (phenotyping) smoking status is needed to facilitate genetic discovery. Using established DNA methylation sites from blood samples as a criterion standard for smoking behavior, we compare... more
A validated, scalable approach to characterizing (phenotyping) smoking status is needed to facilitate genetic discovery. Using established DNA methylation sites from blood samples as a criterion standard for smoking behavior, we compare three candidate electronic medical record (EMR) smoking metrics based on longitudinal EMR text notes. With data from the Veterans Aging Cohort Study (VACS), we employed a validated algorithm to translate each smoking-related text note into current, past or never categories. We compared three alternative summary characterizations of smoking: most recent, modal and trajectories using descriptive statistics and Spearman's correlation coefficients. Logistic regression and area under the curve analyses were used to compare the associations of these phenotypes with the DNA methylation sites, cg05575921 and cg03636183, which are known to have strong associations with current smoking. DNA methylation data were available from the VACS Biomarker Cohort (VA...
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Viral suppression is a primary marker of HIV treatment success. Persons with HIV are at increased risk for AIDS-defining cancer (ADC) and several types of non-AIDS-defining cancer (NADC), some of which are caused by oncogenic viruses. To... more
Viral suppression is a primary marker of HIV treatment success. Persons with HIV are at increased risk for AIDS-defining cancer (ADC) and several types of non-AIDS-defining cancer (NADC), some of which are caused by oncogenic viruses. To determine whether viral suppression is associated with decreased cancer risk. Prospective cohort. Department of Veterans Affairs. HIV-positive veterans (n = 42 441) and demographically matched uninfected veterans (n = 104 712) from 1999 to 2015. Standardized cancer incidence rates and Poisson regression rate ratios (RRs; HIV-positive vs. uninfected persons) by viral suppression status (unsuppressed: person-time with HIV RNA levels ≥500 copies/mL; early suppression: initial 2 years with HIV RNA levels <500 copies/mL; long-term suppression: person-time after early suppression with HIV RNA levels <500 copies/mL). Cancer incidence for HIV-positive versus uninfected persons was highest for unsuppressed persons (RR, 2.35 [95% CI, 2.19 to 2.51]), low...
Research Interests: Incidence Geometry, Cancer, General Internal Medicine, Infectious Diseases, Medicine, and 15 moreHumans, Internal Medicine, Clinical research, Female, Infection, Male, Incidence, Aged, Middle Aged, Hiv Aids, Adult, Medicine and Health Sciences, Case Control Studies, Medical and Health Sciences, and HIV infections
Lung cancer is the leading cause of non-AIDS-defining cancer deaths among HIV-infected individuals. Although lung cancer screening with low-dose computed tomography (LDCT) is endorsed by multiple national organizations, whether... more
Lung cancer is the leading cause of non-AIDS-defining cancer deaths among HIV-infected individuals. Although lung cancer screening with low-dose computed tomography (LDCT) is endorsed by multiple national organizations, whether HIV-infected individuals would have similar benefit as uninfected individuals from lung cancer screening is unknown. Our objective was to determine the benefits and harms of lung cancer screening among HIV-infected individuals. We modified an existing simulation model, the Lung Cancer Policy Model, for HIV-infected patients. Veterans Aging Cohort Study, Kaiser Permanente Northern California HIV Cohort, and medical literature. HIV-infected current and former smokers. Lifetime. Population. Annual LDCT screening from ages 45, 50, or 55 until ages 72 or 77 years. Benefits assessed included lung cancer mortality reduction and life-years gained; harms assessed included numbers of LDCT examinations, false-positive results, and overdiagnosed cases. For HIV-infected p...
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Aging people living with HIV (PLWH) face an increased burden of comorbidities, including chronic obstructive pulmonary disease (COPD). The impact of COPD on mortality in HIV remains unclear. We examined associations between markers of... more
Aging people living with HIV (PLWH) face an increased burden of comorbidities, including chronic obstructive pulmonary disease (COPD). The impact of COPD on mortality in HIV remains unclear. We examined associations between markers of COPD and mortality among PLWH and uninfected subjects. Longitudinal analysis of the Examinations of HIV-Associated Lung Emphysema (EXHALE) cohort study. EXHALE includes 196 PLWH and 165 uninfected smoking-matched subjects who underwent pulmonary function testing and CT scans to define COPD and were followed. We determined associations between markers of COPD with mortality using multivariable Cox regression models, adjusted for smoking and the VACS Index, a validated predictor of mortality in HIV. Median follow-up time was 6.9 years; the mortality rate was 2.7 per 100-person-years among PLWH and 1.7 per 100-person-years among uninfected subjects (p = 0.11). The VACS Index was associated with mortality in both PLWH and uninfected subjects. In multivaria...
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The epidemiology and prognostic impact of increased pulmonary pressure among HIV-infected individuals in the antiretroviral therapy era is not well described. This study evaluated 8,296 veterans referred for echocardiography with reported... more
The epidemiology and prognostic impact of increased pulmonary pressure among HIV-infected individuals in the antiretroviral therapy era is not well described. This study evaluated 8,296 veterans referred for echocardiography with reported pulmonary artery systolic pressure (PASP) estimates from the Veterans Aging Cohort study, an observational cohort of HIV-infected and uninfected veterans matched by age, sex, race/ethnicity, and clinical site. The primary outcome was adjusted mortality by HIV status. PASP was reported in 2,831 HIV-infected and 5,465 HIV-uninfected veterans (follow up 3.8±2.6 years). As compared to uninfected veterans, HIV infected veterans with HIV viral load >500 copies/ml (odds ratio (OR)=1.27, 95% CI=1.05-1.54) and those with CD4 cell count<200 cells/mm3 (OR=1.28, 95% CI=1.02-1.60) had a higher prevalence of PASP≥40 mmHg. As compared to uninfected veterans with a PASP<40mmHg, HIV-infected veterans with a PASP≥40 mmHg had an increased risk of death (adju...
Research Interests: Aging, Electronic Health Records, Medicine, Comorbidity, Echocardiography, and 15 moreHumans, Internal Medicine, Hypertension, Female, Male, Cohort Study, Cohort, Aged, Middle Aged, Human immunodeficiency virus, Adult, Confidence Interval, Cohort Studies, Medical and Health Sciences, and HIV infections
With improved survival, heart failure (HF) has become a major complication for individuals with human immunodeficiency virus (HIV) infection. It is unclear if this risk extends to different types of HF in the antiretroviral therapy (ART)... more
With improved survival, heart failure (HF) has become a major complication for individuals with human immunodeficiency virus (HIV) infection. It is unclear if this risk extends to different types of HF in the antiretroviral therapy (ART) era. Determining whether HIV infection is associated with HF with reduced ejection fraction (HFrEF), HF with preserved ejection fraction (HFpEF), or both is critical because HF types differ with respect to underlying mechanism, treatment, and prognosis. To investigate whether HIV infection increases the risk of future HFrEF and HFpEF and to assess if this risk varies by sociodemographic and HIV-specific factors. This study evaluated 98 015 participants without baseline cardiovascular disease from the Veterans Aging Cohort Study, an observational cohort of HIV-infected veterans and uninfected veterans matched by age, sex, race/ethnicity, and clinical site, enrolled on or after April 1, 2003, and followed up through September 30, 2012. The dates of th...
Research Interests: Cardiology, Risk assessment, Medicine, Heart Failure, Humans, and 15 moreInternal Medicine, Female, Male, Cohort, Risk factors, Middle Aged, Adult, Risk Factors, Risk Assessment, Ejection Fraction, Proportional Hazards Models, Case Control Studies, Cohort Studies, Heart Failure WIth Preserved Ejection Fraction, and HIV infections
As HIV-infected persons on combination antiretroviral therapy (ART) are living longer and rates of opportunistic infections have declined, serious non-AIDS-related diseases account for an increasing proportion of deaths. Consistent with... more
As HIV-infected persons on combination antiretroviral therapy (ART) are living longer and rates of opportunistic infections have declined, serious non-AIDS-related diseases account for an increasing proportion of deaths. Consistent with these changes, non-AIDS-related illnesses account for the majority of ICU admissions in more recent studies, in contrast to earlier eras of the AIDS epidemic. Although mortality after ICU admission has improved significantly since the earliest HIV era, it remains substantial. In this article, we discuss the current state of knowledge regarding the impact of ART on incidence, etiology, and outcomes of critical illness among HIV-infected patients. In addition, we consider issues related to administration of ART in the ICU and identify important areas of future research.
Research Interests: Incidence Geometry, Quality of life, Survival Analysis, Medicine, Antiretroviral Therapy, and 14 moreHumans, Etiology, Incidence, Risk factors, Patient Admission, Apache, Intensive Care Medicine, Risk Factors, Intensive Care Units, Hospital Mortality, Critical Illness, Health Services Accessibility, Anti-retroviral agents, and HIV infections
Weight gain after antiretroviral therapy (ART) initiation is common but its implication for mortality is unknown. We evaluated weight change in the first year after ART initiation and its association with subsequent mortality. HIV... more
Weight gain after antiretroviral therapy (ART) initiation is common but its implication for mortality is unknown. We evaluated weight change in the first year after ART initiation and its association with subsequent mortality. HIV infected patients from the Veterans Aging Cohort Study (VACS) who initiated ART between 2000 and 2008 with weight recorded at baseline and 1 year later, were followed another 5 years for mortality. Baseline body mass index (BMI in kg/m(2)) was classified as underweight (<18.5), normal (18.5-24.9), overweight (25-29.9), and obese (≥30). We used multivariable Cox models to assess mortality risk with adjustment for disease severity using the VACS Index. The sample consisted of 4184 men and 127 women with mean age of 47.9±10.0 years. After 1 year of ART, median weight change was 5.9 (IQR -2.9, 17.0) pounds. Weight gain after ART initiation was associated with lower mortality among underweight and normal weight patients. A minimum threshold of 10 to <2...
Research Interests: Medicine, HIV, Biological Sciences, Prospective studies, Overweight, and 15 moreHumans, Weight Loss, Female, Male, Veterans, Body Mass Index, Underweight, Middle Aged, Adult, Body Weight, Weight Gain, Clinical Infectious Diseases, Anti-retroviral agents, Medical and Health Sciences, and HIV infections
Research Interests: Cancer, Medicine, HIV, Lung Cancer, Clinical Practice, and 15 morePopulation, Humans, Female, Male, Cancer Screening, Hepatocellular Carcinoma, Psychological Intervention, Conceptual Model, Hiv Infection, Life Expectancy, Human immunodeficiency virus, Neoplasms, General Population, Early detection of cancer, and HIV infections
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Research Interests: Mortality, Medicine, Humans, Internal Medicine, Hospitalization, and 15 moreFemale, Male, Risk factors, Phenotype, Clinical Sciences, Aged, Middle Aged, Adult, Proportional hazards model, Geriatric Assessment, Risk Factors, Proportional Hazards Models, Confidence Interval, Frail elderly, and HIV infections
Research Interests: Marketing, Algorithms, Electronic Health Records, Medicine, Humans, and 15 moreSmoking Cessation, Smoking, Female, Male, Psychological Intervention, Data Collection, Cohort, Clinical Sciences, Middle Aged, Adult, Public health systems and services research, Reproducibility of Results, Health surveys, Self report, and Cohort Studies
Research Interests: Medicine, Applied Economics, Multivariate Analysis, Humans, United States, and 13 moreFemale, Alcohol Drinking, Male, Veterans, Medical Care, Middle Aged, International Classification of Diseases, Public health systems and services research, Hiv seropositivity, Alcohol Use, Medical Audit, Department of Veterans Affairs, and Cohort Studies
Research Interests: General Internal Medicine, Comorbidity, Humans, COPD, Internal Medicine, and 15 moreGeneral, Health related Quality of Life, Female, Male, Lung Diseases, Hiv Infection, Clinical Sciences, International Classification of Diseases, Clinical Data, Highly Active Antiretroviral Therapy, Chronic obstructive pulmonary disease, Alcohol Use, Confidence Interval, HIV infections, and Cigarette Smoke
Research Interests: General Internal Medicine, Medicine, Logistic Regression, HIV, Antiretroviral Therapy, and 15 moreHumans, General, Infectious Disease, Female, Male, Awareness, Clinical Sciences, Middle Aged, Professional Practice, Health Care Provider, Observational Study, Electronic Medical Record, Health Personnel, HIV infections, and Cigarette Smoke
Research Interests: Emergency Medicine, Aging, Medicine, Comorbidity, Logistic Regression, and 15 moreCritical Care, HIV, Humans, INTENSIVE CARE, Hospitalization, Female, Male, Clinical Sciences, Intensive Care Unit, Middle Aged, Adult, Medicine and Health Sciences, Cohort Studies, HIV infections, and Medical Intensive Care Unit
Research Interests: Immunology, Cancer, Medicine, Humans, Disease, and 4 moreImmune system, Neoplasms, Age Factors, and HIV infections
Research Interests: Aging, Comorbidity, Logistic Regression, Hospitals, Critical Care Medicine, and 15 moreHumans, Internal Medicine, Female, Diagnosis, Male, Cohort, Medicare, Clinical Sciences, Aged, Human immunodeficiency virus, Age Factors, Differential, Intensive Care Units, health status indicators, and HIV infections
Research Interests: Immunology, Inflammation, Medicine, Comorbidity, Biological Sciences, and 15 moreHumans, Internal Medicine, Female, Male, Aged, Adult, Biological markers, Medicine and Health Sciences, Logistic Models, Clinical Infectious Diseases, Cohort Studies, Interleukin, Blood coagulation disorders, Medical and Health Sciences, and HIV infections
Research Interests:
Research Interests: Epidemiology, Immunology, Incidence Geometry, Medicine, Biological Sciences, and 15 moreHumans, Male, Bacteria, Cohort Study, Hiv Infection, Incidence, Clinical Sciences, Middle Aged, Pneumococcal Vaccine, Hemoglobins, Clinical Infectious Diseases, Cohort Studies, Medical and Health Sciences, Paediatrics and reproductive medicine, and HIV infections
ABSTRACTSerologic studies can provide important insights into the epidemiology and transmission ofPneumocystis jirovecii. Exposure toP. jiroveciican be assessed by serum antibody responses to recombinant antigens from the major surface... more
ABSTRACTSerologic studies can provide important insights into the epidemiology and transmission ofPneumocystis jirovecii. Exposure toP. jiroveciican 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 toP. jiroveciiin 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 result...