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1.
Alcohol Clin Exp Res ; 2021 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-33837975

RESUMO

BACKGROUND: Objective measurement of alcohol consumption is important for clinical care and research. Adjusting for self-reported alcohol use, we conducted an individual participant data (IPD) meta-analysis to examine factors associated with the sensitivity of phosphatidylethanol (PEth), an alcohol metabolite, among persons self-reporting unhealthy alcohol consumption. METHODS: We identified 21 eligible studies and obtained 4073 observations from 3085 participants with Alcohol Use Disorders Identification Test - Consumption (AUDIT-C) positive scores (≥3 for women and ≥4 for men) and PEth measurements. We conducted one-step IPD meta-analysis using mixed-effects models with random intercepts for study site. We examined the associations between demographic (sex, race/ethnicity, and age) and biologic (body mass index -- BMI, hemoglobin, HIV status, liver fibrosis, and venous versus finger-prick blood collection) variables with PEth sensitivity (PEth≥8 ng/mL), adjusting for level of alcohol use using the AUDIT-C score. RESULTS: One-third (31%) of participants were women, 32% were African, 28% African American, 28% White, and 12% other race/ethnicity. PEth sensitivity (i.e. ≥8 ng/mL) was 81.8%. After adjusting for AUDIT-C, we found no associations of sex, age, race/ethnicity, or method of blood collection with PEth sensitivity. In models that additionally included biologic variables, those with higher hemoglobin and indeterminate and advanced liver fibrosis had significantly higher odds of PEth sensitivity; those with higher BMI and those living with HIV had significantly lower odds of PEth sensitivity. African Americans and Africans had higher odds of PEth sensitivity compared to whites in models that included biologic variables. CONCLUSIONS: Among people reporting unhealthy alcohol use, several biological factors (hemoglobin, BMI, liver fibrosis, and HIV status) were associated with PEth sensitivity. Race/ethnicity was associated with PEth sensitivity in some models; age, sex and method of blood collection were not. Clinicians should be aware of these factors, and researchers should consider adjusting analyses for these characteristics where possible.

2.
PLoS One ; 16(3): e0248128, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33730088

RESUMO

BACKGROUND: The COVID-19 pandemic remains a significant global threat. However, despite urgent need, there remains uncertainty surrounding best practices for pharmaceutical interventions to treat COVID-19. In particular, conflicting evidence has emerged surrounding the use of hydroxychloroquine and azithromycin, alone or in combination, for COVID-19. The COVID-19 Evidence Accelerator convened by the Reagan-Udall Foundation for the FDA, in collaboration with Friends of Cancer Research, assembled experts from the health systems research, regulatory science, data science, and epidemiology to participate in a large parallel analysis of different data sets to further explore the effectiveness of these treatments. METHODS: Electronic health record (EHR) and claims data were extracted from seven separate databases. Parallel analyses were undertaken on data extracted from each source. Each analysis examined time to mortality in hospitalized patients treated with hydroxychloroquine, azithromycin, and the two in combination as compared to patients not treated with either drug. Cox proportional hazards models were used, and propensity score methods were undertaken to adjust for confounding. Frequencies of adverse events in each treatment group were also examined. RESULTS: Neither hydroxychloroquine nor azithromycin, alone or in combination, were significantly associated with time to mortality among hospitalized COVID-19 patients. No treatment groups appeared to have an elevated risk of adverse events. CONCLUSION: Administration of hydroxychloroquine, azithromycin, and their combination appeared to have no effect on time to mortality in hospitalized COVID-19 patients. Continued research is needed to clarify best practices surrounding treatment of COVID-19.


Assuntos
Antivirais/uso terapêutico , Azitromicina/uso terapêutico , Hidroxicloroquina/uso terapêutico , Pandemias/prevenção & controle , Gerenciamento de Dados/métodos , Quimioterapia Combinada/métodos , Feminino , Hospitalização , Humanos , Masculino , /efeitos dos fármacos
4.
Lancet ; 397(10279): 1095-1106, 2021 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-33617774

RESUMO

The HIV epidemic in the USA began as a bicoastal epidemic focused in large cities but, over nearly four decades, the epidemiology of HIV has changed. Public health surveillance data can inform an understanding of the evolution of the HIV epidemic in terms of the populations and geographical areas most affected. We analysed publicly available HIV surveillance data and census data to describe: current HIV prevalence and new HIV diagnoses by region, race or ethnicity, and age; trends in HIV diagnoses over time by HIV acquisition risk and age; and the distribution of HIV prevalence by geographical area. We reviewed published literature to explore the reasons for the current distribution of HIV cases and important disparities in HIV prevalence. We identified opportunities to improve public health surveillance systems and uses of data for planning and monitoring public health responses. The current US HIV epidemic is marked by geographical concentration in the US South and profound disparities between regions and by race or ethnicity. Rural areas vary in HIV prevalence; rural areas in the South are more likely to have a high HIV prevalence than rural areas in other US Census regions. Ongoing disparities in HIV in the South are probably driven by the restricted expansion of Medicaid, health-care provider shortages, low health literacy, and HIV stigma. HIV diagnoses overall declined in 2009-18, but HIV diagnoses among individuals aged 25-34 years increased during the same period. HIV diagnoses decreased for all risk groups in 2009-18; among men who have sex with men (MSM), new diagnoses decreased overall and for White MSM, remained stable for Black MSM, and increased for Hispanic or Latino MSM. Surveillance data indicate profound and ongoing disparities in HIV cases, with disproportionate impact among people in the South, racial or ethnic minorities, and MSM.

5.
BMJ ; 372: n311, 2021 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-33574135

RESUMO

OBJECTIVE: To evaluate whether early initiation of prophylactic anticoagulation compared with no anticoagulation was associated with decreased risk of death among patients admitted to hospital with coronavirus disease 2019 (covid-19) in the United States. DESIGN: Observational cohort study. SETTING: Nationwide cohort of patients receiving care in the Department of Veterans Affairs, a large integrated national healthcare system. PARTICIPANTS: All 4297 patients admitted to hospital from 1 March to 31 July 2020 with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and without a history of anticoagulation. MAIN OUTCOME MEASURES: The main outcome was 30 day mortality. Secondary outcomes were inpatient mortality, initiating therapeutic anticoagulation (a proxy for clinical deterioration, including thromboembolic events), and bleeding that required transfusion. RESULTS: Of 4297 patients admitted to hospital with covid-19, 3627 (84.4%) received prophylactic anticoagulation within 24 hours of admission. More than 99% (n=3600) of treated patients received subcutaneous heparin or enoxaparin. 622 deaths occurred within 30 days of hospital admission, 513 among those who received prophylactic anticoagulation. Most deaths (510/622, 82%) occurred during hospital stay. Using inverse probability of treatment weighted analyses, the cumulative incidence of mortality at 30 days was 14.3% (95% confidence interval 13.1% to 15.5%) among those who received prophylactic anticoagulation and 18.7% (15.1% to 22.9%) among those who did not. Compared with patients who did not receive prophylactic anticoagulation, those who did had a 27% decreased risk for 30 day mortality (hazard ratio 0.73, 95% confidence interval 0.66 to 0.81). Similar associations were found for inpatient mortality and initiation of therapeutic anticoagulation. Receipt of prophylactic anticoagulation was not associated with increased risk of bleeding that required transfusion (hazard ratio 0.87, 0.71 to 1.05). Quantitative bias analysis showed that results were robust to unmeasured confounding (e-value lower 95% confidence interval 1.77 for 30 day mortality). Results persisted in several sensitivity analyses. CONCLUSIONS: Early initiation of prophylactic anticoagulation compared with no anticoagulation among patients admitted to hospital with covid-19 was associated with a decreased risk of 30 day mortality and no increased risk of serious bleeding events. These findings provide strong real world evidence to support guidelines recommending the use of prophylactic anticoagulation as initial treatment for patients with covid-19 on hospital admission.


Assuntos
Anticoagulantes/uso terapêutico , Enoxaparina/uso terapêutico , Tromboembolia/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Enoxaparina/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Admissão do Paciente , Tromboembolia/virologia , Fatores de Tempo , Estados Unidos/epidemiologia
6.
JAMA Netw Open ; 4(2): e2037512, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33595662

RESUMO

Importance: People with HIV (PWH) are often coinfected with hepatitis B virus (HBV) and/or hepatitis C virus (HCV), leading to increased risk of developing hepatocellular carcinoma (HCC), but few cohort studies have had sufficient power to describe the trends of HCC incidence and risk among PWH in the combination antiretroviral therapy (cART) era. Objective: To determine the temporal trends of HCC incidence rates (IRs) and to compare rates by risk factors among PWH in the cART era. Design, Setting, and Participants: This cohort study used data from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) study, which was conducted between 1996 and 2015. NA-ACCORD pooled individual-level data from 22 HIV clinical and interval cohorts of PWH in the US and Canada. PWH aged 18 years or older with available CD4 cell counts and HIV RNA data were enrolled. Data analyses were completed in March 2020. Exposures: HBV infection was defined as detection of either HBV surface antigen, HBV e antigen, or HBV DNA in serum or plasma any time during observation. HCV infection was defined by detection of anti-HCV seropositivity, HCV RNA, or detectable genotype in serum or plasma at any time under observation. Main Outcomes and Measures: HCC diagnoses were identified on the basis of review of medical records or cancer registry linkage. Results: Of 109 283 PWH with 723 441 person-years of follow-up, the median (interquartile range) age at baseline was 43 (36-51) years, 93 017 (85.1%) were male, 44 752 (40.9%) were White, 44 322 (40.6%) were Black, 21 343 (19.5%) had HCV coinfection, 6348 (5.8%) had HBV coinfection, and 2082 (1.9%) had triple infection; 451 individuals received a diagnosis of HCC by 2015. Between the early (1996-2000) and modern (2006-2015) cART eras, the crude HCC IR increased from 0.28 to 0.75 case per 1000 person-years. HCC IRs remained constant among HIV-monoinfected persons or those coinfected with HBV, but from 1996 to 2015, IRs increased among PWH coinfected with HCV (from 0.34 cases/1000 person-years in 1996 to 2.39 cases/1000 person-years in 2015) or those with triple infection (from 0.65 cases/1000 person-years in 1996 to 4.49 cases/1000 person-years in 2015). Recent HIV RNA levels greater than or equal to 500 copies/mL (IR ratio, 1.8; 95% CI, 1.4-2.4) and CD4 cell counts less than or equal to 500 cells/µL (IR ratio, 1.3; 95% CI, 1.0-1.6) were associated with higher HCC risk in the modern cART era. People who injected drugs had higher HCC risk compared with men who had sex with men (IR ratio, 2.0; 95% CI, 1.3-2.9), adjusted for HBV-HCV coinfection. Conclusions and Relevance: HCC rates among PWH increased significantly over time from 1996 to 2015. PWH coinfected with viral hepatitis, those with higher HIV RNA levels or lower CD4 cell counts, and those who inject drugs had higher HCC risk.

7.
BMJ Open ; 11(1): e041734, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33419911

RESUMO

OBJECTIVES: As people living with HIV (PLWH) live longer, morbidity and mortality from non-AIDS comorbidities have emerged as major concerns. Our objective was to compare prevalence trends and age at diagnosis of nine chronic age-associated comorbidities between individuals living with and without HIV. DESIGN AND SETTING: This population-based cohort study used longitudinal cohort data from all diagnosed antiretroviral-treated PLWH and 1:4 age-sex-matched HIV-negative individuals in British Columbia, Canada. PARTICIPANTS: The study included 8031 antiretroviral-treated PLWH and 32 124 HIV-negative controls (median age 40 years, 82% men). Eligible participants were ≥19 years old and followed for ≥1 year during 2000 to 2012. PRIMARY AND SECONDARY OUTCOME MEASURES: The presence of non-AIDS-defining cancers, diabetes, osteoarthritis, hypertension, Alzheimer's and/or non-HIV-related dementia, cardiovascular, kidney, liver and lung diseases were identified from provincial administrative databases. Beta regression assessed annual age-sex-standardised prevalence trends and Kruskal-Wallis tests compared the age at diagnosis of comorbidities stratified by rate of healthcare encounters. RESULTS: Across study period, the prevalence of all chronic age-associated comorbidities, except hypertension, were higher among PLWH compared with their community-based HIV-negative counterparts; as much as 10 times higher for liver diseases (25.3% vs 2.1%, p value<0.0001). On stratification by healthcare encounter rates, PLWH experienced most chronic age-associated significantly earlier than HIV-negative controls, as early as 21 years earlier for Alzheimer's and/or dementia. CONCLUSIONS: PLWH experienced higher prevalence and earlier age at diagnosis of non-AIDS comorbidities than their HIV-negative controls. These results stress the need for optimised screening for comorbidities at earlier ages among PLWH, and a comprehensive HIV care model that integrates prevention and treatment of chronic age-associated conditions. Additionally, the robust methodology developed in this study, which addresses concerns on the use of administrative health data to measure prevalence and incidence, is reproducible to other settings.

8.
Drug Alcohol Depend ; 219: 108481, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33429295

RESUMO

INTRODUCTION: Smoking tobacco and unhealthy alcohol use may negatively influence HIV care continuum outcomes but have not been examined in combination. METHODS: Participants were people with HIV (PWH) in Kaiser Permanente Northern California. Predictors included smoking status and unhealthy alcohol use (exceeding daily and/or weekly limits) reported by patients during primary care screening (index date). Outcomes were based on not achieving the following steps in the care continuum: linkage to HIV care (≥1 visit within 90 days of newly identified HIV diagnosis), retention (2+ in-person visits, 60+ days apart) and HIV RNA control (<75 copies/mL). Adjusted odds ratios (ORs) were obtained from separate logistic regression models for each outcome associated with smoking and unhealthy alcohol use independently and combined. RESULTS: The overall sample (N = 8958) had a mean age of 48.0 years; was 91.3 % male; 54.0 % white, 17.6 % Latino, 15.1 % black, and 9.6 % other race/ethnicity. Smoking was associated with higher odds of not being linked to HIV care (OR = 1.60 [95 % CI 1.03-2.48]), not retained (OR = 1.30 [95 % CI 1.13-1.50]), and HIV RNA not in control (OR = 1.91 [95 % CI 1.60-2.27]). Alcohol measures were not independently associated with outcomes. The combination of unhealthy alcohol use and smoking (versus neither) was associated with higher odds of not being linked to care (OR = 2.83 [95 % CI 1.40-5.71]), although the interaction did not reach significance (p = 0.18). CONCLUSIONS: In this large sample of PWH in an integrated health care system, smoking, both independently and in combination with unhealthy alcohol use, was associated with worse HIV care continuum outcomes.

9.
J Am Heart Assoc ; 9(23): e017645, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33222591

RESUMO

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 compared with HIV-uninfected (hazard ratio [HR], 0.89; 95% CI, 0.70-1.12), but HIV infection was associated with higher mortality risk (HR, 1.49; 95% CI, 1.16-1.90). In models stratified by HIV status, CAP severity was significantly associated with incident CVD and 30-day mortality in PLWH and patients uninfected with HIV. Conclusions In this study, the risk of CVD events during or after hospitalization for CAP was similar in PLWH and patients uninfected with HIV, after adjusting for known CVD risk factors and CAP severity. HIV infection, however, was associated with increased 30-day mortality after CAP hospitalization in multivariable-adjusted models. PLWH should be included in future studies evaluating mechanisms and prevention of CVD events after CAP.

10.
PLoS One ; 15(11): e0241825, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33175863

RESUMO

BACKGROUND: Available COVID-19 mortality indices are limited to acute inpatient data. Using nationwide medical administrative data available prior to SARS-CoV-2 infection from the US Veterans Health Administration (VA), we developed the VA COVID-19 (VACO) 30-day mortality index and validated the index in two independent, prospective samples. METHODS AND FINDINGS: We reviewed SARS-CoV-2 testing results within the VA between February 8 and August 18, 2020. The sample was split into a development cohort (test positive between March 2 and April 15, 2020), an early validation cohort (test positive between April 16 and May 18, 2020), and a late validation cohort (test positive between May 19 and July 19, 2020). Our logistic regression model in the development cohort considered demographics (age, sex, race/ethnicity), and pre-existing medical conditions and the Charlson Comorbidity Index (CCI) derived from ICD-10 diagnosis codes. Weights were fixed to create the VACO Index that was then validated by comparing area under receiver operating characteristic curves (AUC) in the early and late validation cohorts and among important validation cohort subgroups defined by sex, race/ethnicity, and geographic region. We also evaluated calibration curves and the range of predictions generated within age categories. 13,323 individuals tested positive for SARS-CoV-2 (median age: 63 years; 91% male; 42% non-Hispanic Black). We observed 480/3,681 (13%) deaths in development, 253/2,151 (12%) deaths in the early validation cohort, and 403/7,491 (5%) deaths in the late validation cohort. Age, multimorbidity described with CCI, and a history of myocardial infarction or peripheral vascular disease were independently associated with mortality-no other individual comorbid diagnosis provided additional information. The VACO Index discriminated mortality in development (AUC = 0.79, 95% CI: 0.77-0.81), and in early (AUC = 0.81 95% CI: 0.78-0.83) and late (AUC = 0.84, 95% CI: 0.78-0.86) validation. The VACO Index allows personalized estimates of 30-day mortality after COVID-19 infection. For example, among those aged 60-64 years, overall mortality was estimated at 9% (95% CI: 6-11%). The Index further discriminated risk in this age stratum from 4% (95% CI: 3-7%) to 21% (95% CI: 12-31%), depending on sex and comorbid disease. CONCLUSION: Prior to infection, demographics and comorbid conditions can discriminate COVID-19 mortality risk overall and within age strata. The VACO Index reproducibly identified individuals at substantial risk of COVID-19 mortality who might consider continuing social distancing, despite relaxed state and local guidelines.


Assuntos
Infecções por Coronavirus/mortalidade , Pneumonia Viral/mortalidade , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Betacoronavirus/isolamento & purificação , Comorbidade , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Bases de Dados Factuais , Grupos Étnicos , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Curva ROC , Fatores de Risco , Saúde dos Veteranos , Adulto Jovem
11.
AIDS ; 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33181533

RESUMO

OBJECTIVE: To determine whether statin exposure is associated with decreased cancer and mortality risk among persons with HIV (PWH) and uninfected persons. Statins appear to have immunomodulatory and anti-inflammatory effects and may reduce cancer risk, particularly among PWH as they experience chronic inflammation and immune activation. DESIGN: Propensity score matched cohort of statin-exposed and unexposed patients from 2002-2017 in the Veterans Aging Cohort Study (VACS), a large cohort with cancer registry linkage and detailed pharmacy data. METHODS: We calculated Cox regression hazard ratios (HRs) and 95% confidence intervals (CI) associated with statin use for all cancers, microbial cancers (associated with bacterial or oncovirus coinfection), non-microbial cancers, and mortality. RESULTS: The propensity score-matched sample (N = 47,940) included 23,970 statin initiators (31% PWH). Incident cancers were diagnosed in 1,160 PWH and 2,116 uninfected patients. Death was reported in 1,667 (7.0%) statin-exposed, and 2,215 (9.2%) unexposed patients. Statin use was associated with 24% decreased risk of microbial associated cancers (HR 0.76; 95% CI 0.69-0.85), but was not associated with non-microbial cancer risk (HR 1.00; 95% CI 0.92-1.09). Statin use was associated with 33% lower risk of death overall (HR 0.67; 95% CI 0.63-0.72). Results were similar in analyses stratified by HIV status, except for non-Hodgkin lymphoma where statin use was associated with reduced risk (HR 0.56; 95% CI 0.38-0.83) for PWH, but not for uninfected (p-interaction = 0.012). CONCLUSIONS: In both PWH and uninfected, statin exposure was associated with lower risk of microbial, but not non-microbial cancer incidence, and with decreased mortality.

12.
J Acquir Immune Defic Syndr ; 85(5): 530-534, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33185999

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) may develop in the absence of cirrhosis in HIV, and determining how often this occurs can provide insights into mechanisms of carcinogenesis. Studies evaluating the prevalence of cirrhosis in the setting of HCC among people living with HIV (PLWH) often rely on noninvasive markers, such as the Fibrosis-4 Index for Hepatic Fibrosis (FIB-4). However, the accuracy of FIB-4 for cirrhosis in the setting of HCC has not been determined among PLWH. METHODS: We conducted a cross-sectional study among PLWH in the Veterans Aging Cohort Study with VA cancer registry-confirmed HCC diagnosed between 1999 and 2015. FIB-4 was calculated using the age, alanine aminotransferase, aspartate aminotransferase, and platelet count obtained closest to, but within 1 year before, HCC diagnosis. Medical records were reviewed within 1 year before HCC diagnosis to determine the cirrhosis status. We evaluated the area under the receiver-operating characteristic curve and performance characteristics of FIB-4 for confirmed cirrhosis. RESULTS: Incident HCC was diagnosed in 302 PLWH. After medical record review, 203 (67.2%, 95% confidence interval: 61.6% to 72.5%) had evidence of cirrhosis. FIB-4 identified patients with cirrhosis with an area under the receiver-operating characteristic curve of 0.67 (95% confidence interval: 0.60 to 0.73). FIB-4 scores >5.0 had a positive predictive value >80% and specificity of >77%, negative predictive value of <41%, and sensitivity of <45%. CONCLUSION: The accuracy of FIB-4 for cirrhosis in the setting of HIV and HCC is modest and may result in misclassification of cirrhosis in this population.

13.
Pharmacoepidemiol Drug Saf ; 29(11): 1432-1439, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33006179

RESUMO

BACKGROUND: Electronic medical records (EMR) represent a rich source of data, but the value of EMR for health research relies on accurate ascertainment of clinical diagnoses. Identifying diabetes in EMR is complicated by the variety of accepted diagnostic criteria, some of which can be confounded by conditions such as HIV infection. We compared EMR-based criteria for estimating diabetes prevalence and incidence in the Veterans Health Administration (VHA), overall and by HIV status, against physician chart review and adjudication. RESEARCH DESIGN AND METHODS: We used laboratory values (serum glucose and hemoglobin A1c% [HbA1c]), ICD-9 codes, and medication records from the United States Veterans Aging Cohort Study Biomarker Cohort to identify veterans with any indication of diabetes in the EMR for subsequent physician adjudication. Sensitivity, specificity, PPV, NPV, and kappa statistics were used to evaluate agreement of EMR-based diabetes diagnoses with chart review adjudicated diagnoses. RESULTS: EMR entries were reviewed for 1546 persons with HIV (PWH) and 843 HIV-negative participants through 2015. Agreement was at least moderate overall (kappa ≥ 0.42) for all pre-specified measures and among PWH vs HIV-negative, and African-American vs white sub-groups. Having at least one HbA1c ≥6.5% provided substantial agreement with chart adjudication for prevalent and incident diabetes (kappa = 0.89 and 0.73). CONCLUSIONS: Identification of those with diabetes nationally within the VHA can be used in future studies to evaluate treatments, health outcomes, and adjust for diabetes in epidemiologic studies. Our methodology may provide insights for other organizations seeking to use EMR data for accurate determination of diabetes.

14.
J Gen Intern Med ; 35(10): 3140, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33021712

RESUMO

JGIM published the article matched with the editorial in this issue in the July 2020 issue. Our apologies to the authors of the paper and the editorial.

15.
Alcohol Clin Exp Res ; 44(12): 2545-2554, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33067802

RESUMO

BACKGROUND: Unhealthy alcohol use among persons living with HIV (PLWH) is linked to significant morbidity, and use of alcohol services may differ by HIV status. Our objective was to compare unhealthy alcohol use screening and treatment by HIV status in primary care. METHODS: Cohort study of adult (≥18 years) PLWH and HIV-uninfected participants frequency matched 20:1 to PLWH by age, sex, and race/ethnicity who were enrolled in a large integrated healthcare system in the United States, with information ascertained from an electronic health record. Outcomes included unhealthy alcohol screening, prevalence, provider-delivered brief interventions, and addiction specialty care visits. Other predictors included age, sex, race/ethnicity, neighborhood deprivation index, depression, smoking, substance use disorders, Charlson comorbidity index, prior outpatient visits, insurance type, and medical facility. Cox proportional hazards models were used to compute hazard ratios (HR) for the outcomes of time to unhealthy alcohol use screening and time to first addiction specialty visit. Poisson regression with robust standard errors was used to compute prevalence ratios (PR) for other outcomes. RESULTS: 11,235 PLWH and 227,320 HIV-uninfected participants were included. By 4.5 years after baseline, most participants were screened for unhealthy alcohol use (85% of PLWH and 93% of HIV-uninfected), but with a lower rate among PLWH (adjusted HR 0.84, 95% CI 0.82 to 0.85). PLWH were less likely, compared with HIV-uninfected participants, to report unhealthy drinking among those screened (adjusted PR 0.74, 95% CI 0.69 to 0.79), and among those who screened positive, less likely to receive brief interventions (adjusted PR 0.82, 95% CI 0.75 to 0.90), but more likely (adjusted HR 1.7, 95% CI 1.2 to 2.4) to have an addiction specialty visit within 1 year. CONCLUSIONS: Unhealthy alcohol use was lower in PLWH, but the treatment approach by HIV status differed. PLWH reporting unhealthy alcohol use received less brief interventions and more addiction specialty care than HIV-uninfected participants.

16.
Alcohol Clin Exp Res ; 44(11): 2257-2265, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33030753

RESUMO

BACKGROUND: We aimed to investigate the impact of reducing drinking in patients with unhealthy alcohol use on improvement of chronic pain interference, substance use, and psychiatric symptoms. METHODS: We analyzed longitudinal data from 2003 to 2015 in the Veterans Aging Cohort Study, a prospective, multisite observational study of US veterans, by emulating a hypothetical randomized trial (a target trial). Alcohol use was assessed using the Alcohol Use Disorders Identification Test (AUDIT) questionnaire, and outcome conditions were assessed via validated survey items. Individuals were followed from the first time their AUDIT score was ≥ 8 (baseline), a threshold consistent with unhealthy alcohol use. We compared individuals who reduced drinking (AUDIT < 8) at the next follow-up visit with individuals who did not (AUDIT ≥ 8). We fit separate logistic regression models to estimate odds ratios for improvement of each condition 2 years postbaseline among individuals who had that condition at baseline: moderate or severe pain interference symptoms, tobacco smoking, cannabis use, cocaine use, depressive symptoms, and anxiety symptoms. Inverse probability weighting was used to account for potential selection bias and confounding. RESULTS: Adjusted 2-year odds ratios (95% confidence intervals) for associations between reducing drinking and improvement or resolution of each condition were as follows: 1.49 (0.91, 2.42) for pain interference symptoms, 1.57 (0.93, 2.63) for tobacco smoking, 1.65 (0.92, 2.95) for cannabis use, 1.83 (1.03, 3.27) for cocaine use, 1.11 (0.64, 1.92) for depressive symptoms, and 1.33 (0.80, 2.22) for anxiety symptoms. CONCLUSIONS: We found some evidence for improvement of pain interference symptoms and substance use after reducing drinking among US veterans with unhealthy alcohol use, but confidence intervals were wide.

17.
Epigenetics ; : 1-13, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33092459

RESUMO

Background: With the improved life expectancy of people living with HIV (PLWH), identifying vulnerable subpopulations at high mortality risk is important. Evidences showed that DNA methylation (DNAm) is associated with mortality in non-HIV populations. Here, we established a panel of DNAm biomarkers that can predict mortality risk among PLWH. Methods: 1,081 HIV-positive participants from the Veterans Ageing Cohort Study (VACS) were divided into training (N = 460), validation (N = 114), and testing (N = 507) sets. VACS index was used as a measure of mortality risk among PLWH. Model training and fine-tuning were conducted using the ensemble method in the training and validation sets and prediction performance was assessed in the testing set. The survival analysis comparing the predicted high and low mortality risk groups and the Gene Ontology enrichment analysis of the predictive CpG sites were performed. Results: We selected a panel of 393 CpGs for the ensemble prediction model that showed excellent performance in predicting high mortality risk with an auROC of 0.809 (95%CI: 0.767,0.851) and a balanced accuracy of 0.653 (95%CI: 0.611, 0.693) in the testing set. The high mortality risk group was significantly associated with 10-year mortality (hazard ratio = 1.79, p = 4E-05) compared with low risk group. These 393 CpGs were located in 280 genes enriched in immune and inflammation response pathways. Conclusions: We identified a panel of DNAm features associated with mortality risk in PLWH. These DNAm features may serve as predictive biomarkers for mortality risk among PLWH. Abbreviations: AUC: Area Under Curve; CI: Confidence interval; DMR: differentially methylated region; DNA: Deoxyribonucleic acid; DNAm: DNA methylation; DAVID: Database for Annotation, Visualization, and Integrated Discovery; EWA: epigenome-wide association; FDR: False discovery rate; FWER: Family-wise error rate; GLMNET: elastic-net-regularized generalized linear models; GO: Gene ontology; HIV: Human immunodeficiency virus; HM450K: Human Methylation 450 K BeadChip; k-NN: k-nearest neighbours; NK: Natural killer; PC: Principal component; PLWH: people living with HIV; QC: Quality control; SVM: Support Vector Machines; VACS: Veterans Ageing Cohort Study; XGBoost: Extreme Gradient Boosting Tree.

18.
Open Forum Infect Dis ; 7(10): ofaa441, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33123611

RESUMO

Background: Case reports describe incident sarcoidosis in persons with HIV (PWH). The association between HIV and risk of sarcoidosis, and differences in presentation in PWH, have not been systematically assessed. Methods: Subjects were selected from the Veterans Aging Cohort Study (VACS), a longitudinal cohort study including veterans with HIV and matched uninfected veterans. This was a prospective observational analysis in which we evaluated both the incidence (via incidence rate ratio) and presentation and treatment (by comparison of rates of organ involvement and use of medications) of sarcoidosis in PWH compared with HIV-negative controls. We also assessed risk factors (via Cox regression) associated with the development of sarcoidosis including CD4 count and viral load trajectory. Results: Of 1614 patients evaluated via chart review, 875 (54%) had prevalent sarcoidosis and 325 (20%) had confirmed incident sarcoidosis. Incident sarcoidosis occurred in 59 PWH and 266 uninfected. The incidence of sarcoidosis was lower in PWH than uninfected (incidence rate ratio [IRR], 0.61; 95% CI, 0.46-0.81) and especially low in patients with unsuppressed viremia (IRR, 0.04; 95% CI, 0.02-0.08) compared with uninfected). At diagnosis of sarcoidosis, the median CD4 count among PWH was 409 cells/mm3; 77% had HIV-1 RNA <500 copies/mL. No significant differences were observed between PWH and uninfected in terms of organ involvement, disease severity, or use of oral glucocorticoids. Conclusions: HIV, particularly with persistent viremia, was associated with decreased risk of incident sarcoidosis; severity and treatment were similar between PWH and uninfected.

19.
Nat Commun ; 11(1): 5302, 2020 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-33082346

RESUMO

Here we report a large genome-wide association study (GWAS) for longitudinal smoking phenotypes in 286,118 individuals from the Million Veteran Program (MVP) where we identified 18 loci for smoking trajectory of current versus never in European Americans, one locus in African Americans, and one in Hispanic Americans. Functional annotations prioritized several dozen genes where significant loci co-localized with either expression quantitative trait loci or chromatin interactions. The smoking trajectories were genetically correlated with 209 complex traits, for 33 of which smoking was either a causal or a consequential factor. We also performed European-ancestry meta-analyses for smoking status in the MVP and GWAS & Sequencing Consortium of Alcohol and Nicotine use (GSCAN) (Ntotal = 842,717) and identified 99 loci for smoking initiation and 13 loci for smoking cessation. Overall, this large GWAS of longitudinal smoking phenotype in multiple populations, combined with a meta-GWAS for smoking status, adds new insights into the genetic vulnerability for smoking behavior.


Assuntos
Estudo de Associação Genômica Ampla , Fumar/genética , Afro-Americanos/genética , Estudos de Coortes , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Hispano-Americanos/genética , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Fumar/psicologia
20.
Drug Alcohol Depend ; 217: 108272, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32971391

RESUMO

BACKGROUND: For people with HIV (PWH) and alcohol use disorder (AUD) who initiated behavioral treatment (BAUD) we: 1) describe BAUD intensity and medication (MAUD); and 2) examine whether BAUD and MAUD were associated with changes in HIV-related outcomes (CD4 cell count, HIV-1 viral load [VL], VACS Index score 2.0, and antiretroviral [ARV] adherence) from before to one year after treatment initiation. METHODS: We used Veterans Aging Cohort Study (VACS) data to describe BAUD intensity and MAUD (acamprosate, disulfiram, and naltrexone, gabapentin or topiramate). Linear regression models estimated changes in outcomes and included BAUD, MAUD, age and race/ethnicity. RESULTS: We identified 7830 PWH who initiated BAUD from 01/2008-09/2017. Median age was 53, 60% were African-American and 28% white. BAUD intensity groups were: 1) Single Visit - 35%; 2) Minimal - 44% recieved ∼2 visits during first month; 3) Sustained Moderate - 17% recieved ∼8 visits/month initially; and 4) Intensive - 4% started out receiving ∼14-16 visits/month. Only 9% recieved MAUD, the majority of which was gabapentin. Among those with detectable VL: all HIV-related outcomes improved more among those with more intensive BAUD. Among those with undetectable VL: adherence improved more among those with greater BAUD intensity. MAUD was associated with increased CD4 among those with detectable VL and with improved adherence among both groups. CONCLUSION: Of those with >1 BAUD visit, only 21% received at least moderate BAUD and 9% received at least 6 months of MAUD. Increasing AUD treatment intensity may improve HIV-related outcomes, especially among those with detectable VL.

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