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2.
AIDS Behav ; 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31435887

RESUMO

We contrast three types of abstinence: quit after alcohol associated problems (Q-AP), quit for other reasons (Q-OR), and lifetime abstainer (LTA). We summarized the characteristics of people living with HIV (PLWH), and matched uninfected individuals, by levels of alcohol use and types of abstinence. We then identified factors that differentiate abstinence and determined whether the association with an alcohol biomarker or a genetic polymorphism is improved by differentiating abstinence. Among abstainers, 34% of PLWH and 38% of uninfected were Q-AP; 53% and 53% were Q-OR; and 12% and 10% were LTA. Logistic regression models found smoking, alcohol, cocaine, and hepatitis C increased odds of Q-AP, whereas smoking and marijuana decreased odds of LTA. Differentiating types of abstinence improved association. Q-APs and LTAs can be readily differentiated by an alcohol biomarker and genetic polymorphism. Differentiating type of abstinence may enhance understanding of alcohol health effects.

3.
AIDS Behav ; 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31317364

RESUMO

A better understanding of predisposition to transition to high-dose, long-term opioid therapy after initial opioid receipt could facilitate efforts to prevent opioid use disorder (OUD). We extracted data on 69,268 patients in the Veterans Aging Cohort Study who received any opioid prescription between 1998 and 2015. Using latent growth mixture modelling, we identified four distinguishable dose trajectories: low (53%), moderate (29%), escalating (13%), and rapidly escalating (5%). Compared to low dose trajectory, those in the rapidly escalating dose trajectory were proportionately more European-American (59% rapidly escalating vs. 38% low); had a higher prevalence of HIV (31% vs. 29%) and hepatitis C (18% vs. 12%); and during follow-up, had a higher incidence of OUD diagnoses (13% vs. 3%); were hospitalised more often [18.1/100 person-years (PYs) vs. 12.5/100 PY]; and had higher all-cause mortality (4.7/100 PY vs. 1.8/100 PY, all p < 0.0001). These measures can potentially be used in future prevention research, including genetic discovery.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31339866

RESUMO

BACKGROUND: Medication classes, polypharmacy, hazardous alcohol and illicit substance abuse may exhibit stronger associations with serious falls among persons living with HIV (PLWH) than with uninfected comparators. We investigated whether these associations differed by HIV status. SETTING: Veterans Aging Cohort Study METHODS.: We employed a nested case-control design. Cases (N=13,530) were those who fell. Falls were identified by external cause of injury codes and a machine learning algorithm applied to radiology reports. These were matched to controls (N=67,060) by age, race, sex, HIV status, duration of observation, and baseline date. Risk factors included medication classes, count of unique non-antiretroviral (non-ART) medications, and hazardous alcohol and illicit substance use. We used unconditional logistic regression to evaluate associations. RESULTS: Among PLWH, benzodiazepines (odds ratio (OR) 1.24; 95% confidence interval (CI) 1.08, 1.40) and muscle relaxants (OR 1.29; 95% CI 1.08, 1.46) were associated with serious falls but not among uninfected (p>0.05). In both groups, key risk factors included non-ART medications (per five medications) (OR 1.20, 95% CI 1.17, 1.23), illicit substance use/abuse (OR 1.44; 95% CI 1.34, 1.55), hazardous alcohol use (OR 1.30; 95% CI 1.23, 1.37), and an opioid prescription (OR 1.35; 95% CI 1.29, 1.41). CONCLUSION: Benzodiazepines and muscle relaxants were associated with serious falls among PLWH. Non-ART medication count, hazardous alcohol and illicit substance use, and opioid prescriptions were associated with serious falls in both groups. Prevention of serious falls should focus on reducing specific classes and absolute number of medications and both alcohol and illicit substance use.

5.
Oral Oncol ; 94: 32-40, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31178210

RESUMO

OBJECTIVES: To characterize the representation of women in clinical trials directing the National Comprehensive Cancer Network (NCCN) guidelines for chemotherapy use in head and neck squamous cell carcinoma (HNSCC), as well as the relationship between gender and chemotherapy administration in the definitive treatment of HNSCC in the United States. METHODS: A review of all HNSCC chemotherapy clinical trials cited by the 2018 NCCN guidelines was performed. Sex-based proportions were compared with the corresponding proportions in the general U.S. population of patients with HNSCC between 1985 and 2015, derived from the Surveillance, Epidemiology, and End Results (SEER) program. A second analysis using the National Cancer Database (NCDB), identified 63,544 adult patients diagnosed with stages III-IVB HNSCC between 2004 and 2014 and treated with definitive radiotherapy or chemoradiotherapy. Univariable and multivariable logistic regression analyses were used to identify predictors of chemotherapy administration. RESULTS: While women comprised 26.2% of U.S. patients with HNSCC between 1985 and 2015, they comprised only 17.0% of patients analyzed in U.S. NCCN-cited chemotherapy clinical trials between 1985 and 2017. On multivariable analysis, women had decreased odds of receiving chemotherapy (Odds Ratio [OR]: 0.875; 95% Confidence Interval [CI]: 0.821-0.931; p < 0.001). CONCLUSION: Women are underrepresented in HNSCC chemotherapy clinical trials cited by the national guidelines. Additionally, women are less likely than men to receive definitive chemoradiotherapy as oppose to definitive radiotherapy. Reasons for these disparities warrant further investigation as well as re-evaluation of eligibility criteria and enrollment strategies, in order to improve relevance of clinical trials to women with HNSCC.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31194229

RESUMO

Importance: Though described as an important prognostic indicator, facility case volume thresholds for patients with head and neck squamous cell carcinoma (HNSCC) have not been previously developed to date. Objective: To identify prognostic case volume thresholds of facilities that manage HNSCC. Design, Setting, and Participants: Retrospective analysis of 351 052 HNSCC cases reported from January 1, 2004, through December 31, 2014, by Commission of Cancer-accredited cancer centers from the US National Cancer Database. Data were analyzed from August 1, 2018, to April 5, 2019. Exposures: Treatment of HNSCC at facilities with varying case volumes. Main Outcomes and Measures: Using all-cause mortality outcomes among adult patients with HNSCC, 10 groups with increasing facility case volume were created and thresholds were identified where group survival differed compared with each of the 2 preceding groups (univariate log-rank analysis). Groups were collapsed at these thresholds and the prognostic value was confirmed using multivariable Cox regression. Prognostic meaning of these thresholds was assessed in subgroups by category (localized [I/II] and advanced [III/IV]), without metastasis (M0), with metastasis (M1), and anatomic subsites (nonoropharyngeal HNSCC and oropharyngeal HNSCC with known human papillomavirus status). Results: Of 250 229 eligible patients treated at 1229 facilities in the United States, there were 185 316 (74.1%) men and 64 913 (25.9%) women and the mean (SD) age was 62.8 (12.1) years. Three case volume thresholds were identified (low: ≤54 cases per year; moderate: >54 to ≤165 cases per year; and high: >165 cases per year). Compared with the moderate-volume group, multivariate analysis found that treatment at low-volume facilities (LVFs) was associated with a higher risk of mortality (hazard ratio [HR], 1.09; 99% CI, 1.07-1.11), whereas treatment at high-volume facilities (HVFs) was associated with a lower risk of mortality (HR, 0.92; 99% CI, 0.89-0.94). Subgroup analysis with Bonferroni correction revealed that only the moderate- vs low- threshold had meaningful differences in outcomes in localized stage (I/II) cancers, (LVFs vs moderate-volume facilities [MVFs]: HR, 1.09 [99% CI, 1.05-1.13]; HVF vs MVF: HR, 0.95 [99% CI, 0.90-1.00]), whereas both thresholds were meaningful in advanced stage (III/IV) cancers (LVF vs MVF: HR, 1.09 [99% CI, 1.06-1.12]; HVF vs MVF: HR, 0.91 [99% CI, 0.88-0.94]). Survival differed by prognostic thresholds for both M0 (LVF vs MVF: HR, 1.09 [99% CI, 1.07-1.12]; HVF vs MVF: HR, 0.91 [99% CI, 0.89-0.94]) and nonoropharyngeal HNSCC (LVF vs MVF: HR, 1.10 [99% CI, 1.07-1.13]; HVF vs MVF: HR, 0.93 [99% CI, 0.90-0.97]) site cases, but not for M1 (LVF vs MVF: HR, 1.00 [99% CI, 0.92-1.09]; HVF vs MVF: HR, 0.94 [99% CI, 0.83-1.07]) or oropharyngeal HNSCC cases (when controlling for human papillomavirus status) (LVF vs MVF: HR, 1.10 [99% CI, 0.99-1.23]; HVF vs MVF: HR, 1.07 [99% CI, 0.94-1.22]). Conclusions and Relevance: Higher volume facility threshold results appear to be associated with increases in survival rates for patients treated for HNSCC at MVFs or HVFs compared with LVFs, which suggests that these thresholds may be used as quality markers.

7.
Nat Mater ; 18(7): 732-739, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31209391

RESUMO

Exploratory synthesis in new chemical spaces is the essence of solid-state chemistry. However, uncharted chemical spaces can be difficult to navigate, especially when materials synthesis is challenging. Nitrides represent one such space, where stringent synthesis constraints have limited the exploration of this important class of functional materials. Here, we employ a suite of computational materials discovery and informatics tools to construct a large stability map of the inorganic ternary metal nitrides. Our map clusters the ternary nitrides into chemical families with distinct stability and metastability, and highlights hundreds of promising new ternary nitride spaces for experimental investigation-from which we experimentally realized seven new Zn- and Mg-based ternary nitrides. By extracting the mixed metallicity, ionicity and covalency of solid-state bonding from the density functional theory (DFT)-computed electron density, we reveal the complex interplay between chemistry, composition and electronic structure in governing large-scale stability trends in ternary nitride materials.

8.
Lancet HIV ; 6(8): e509-e517, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31109915

RESUMO

BACKGROUND: We examined the effectiveness of integrated stepped alcohol treatment (ISAT) on alcohol use and HIV outcomes among patients living with HIV and alcohol use disorder. METHODS: In this multisite, randomised controlled trial, conducted in five Veterans Affairs-based HIV clinics in the USA (Atlanta, GA; Brooklyn-Manhattan, NY; Dallas and Houston, TX; and Washington, DC), we recruited people living with HIV and an alcohol use disorder who were not otherwise receiving formal alcohol treatment. Patients were eligible if they were aged 18 years or older, HIV positive, English speaking, and met criteria for alcohol use disorder by the Diagnostic and Statistical Manual for Mental Disorders-IV criteria for alcohol abuse or dependence. Key exclusion criteria included if the patient was acutely suicidal or had a psychiatric condition that affected their ability to participate in counselling interventions, or if they had any medical conditions that would preclude completing the study or cause harm during the course of the study. Using a web-based clinical trial management system, we randomly assigned participants (1:1) to receive ISAT or treatment as usual; patients, investigators, and clinicians were unmasked to allocation. ISAT involved three steps: step 1, addiction physician management, comprising eight sessions; step 2, addiction physician management plus motivational enhancement therapy, comprising four sessions; and step 3, specialty referral. Participants were stepped up at weeks 4 and 12 if they exceeded a priori drinking criteria. Treatment as usual involved referral to substance use treatment services. The primary outcome was number of drinks per week over the past 30 days at week 24 by use of the timeline followback method, assessed in the intention-to-treat population. Adverse events were tracked throughout the study period in all randomly assigned participants. This trial is registered at ClinicalTrials.gov, number NCT01410123. FINDINGS: Between Jan 28, 2013, and July 14, 2017, 128 of 351 patients assessed for eligibility were eligible and randomly assigned to receive ISAT (n=63) or treatment as usual (n=65). Mean age was 54 years (range 23-70), 125 (98%) of 128 participants were men, and 101 (79%) were black. 25 (20%) were lost to follow-up. In the ISAT group, of 57 participants who did not die or withdraw, 30 (52%) advanced to step 2, and 17 (57%) of 30 advanced to step 3. 32 (51%) of 63 participants assigned to ISAT versus 17 (26%) of 65 assigned to treatment as usual received at least one alcohol treatment medication (p=0·004). Participants in both groups decreased their alcohol consumption, but at week 24 we did not detect a difference in number of drinks per week between the groups (least squares mean 10·4 drinks per week [SD 16·5] in the ISAT group vs 15·6 drinks per week [SD 17·6] in the treatment as usual group; adjusted mean difference -4·2, 95% CI -9·4 to 0·9; p=0·11). One adverse event occurred that was possibly related to treatment occurred in the ISAT group (headache). INTERPRETATION: ISAT increases the receipt of alcohol treatment medications and counselling without changes in drinking at week 24. Strategies to implement and enhance ISAT are needed. Future efforts should focus on promoting ISAT with attention to enhancing patient engagement and retention in alcohol-related care. FUNDING: US National Institute on Alcohol Abuse and Alcoholism.

9.
Nat Commun ; 10(1): 2275, 2019 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-31101824

RESUMO

The original version of this Article omitted the following from the Acknowledgements: 'Supported by the Mental Illness Research, Education and Clinical Center of the Veterans Integrated Service Network 4 of the Department of Veterans Affairs.' This has now been corrected in both the PDF and HTML versions of the Article.

10.
Nat Commun ; 10(1): 1499, 2019 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-30940813

RESUMO

Alcohol consumption level and alcohol use disorder (AUD) diagnosis are moderately heritable traits. We conduct genome-wide association studies of these traits using longitudinal Alcohol Use Disorder Identification Test-Consumption (AUDIT-C) scores and AUD diagnoses in a multi-ancestry Million Veteran Program sample (N = 274,424). We identify 18 genome-wide significant loci: 5 associated with both traits, 8 associated with AUDIT-C only, and 5 associated with AUD diagnosis only. Polygenic Risk Scores (PRS) for both traits are associated with alcohol-related disorders in two independent samples. Although a significant genetic correlation reflects the overlap between the traits, genetic correlations for 188 non-alcohol-related traits differ significantly for the two traits, as do the phenotypes associated with the traits' PRS. Cell type group partitioning heritability enrichment analyses also differentiate the two traits. We conclude that, although heavy drinking is a key risk factor for AUD, it is not a sufficient cause of the disorder.


Assuntos
Consumo de Bebidas Alcoólicas/genética , Alcoolismo/genética , Estudo de Associação Genômica Ampla , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Herança Multifatorial , Fenótipo , Polimorfismo de Nucleotídeo Único , Adulto Jovem
11.
J Acquir Immune Defic Syndr ; 81(4): 448-455, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30973541

RESUMO

BACKGROUND: Alcohol use influences HIV disease severity through multiple mechanisms. Whether HIV disease severity is sensitive to changes in alcohol use among people with HIV (PWH) is understudied. SETTING: National Veterans Health Administration. METHODS: Pairs of AUDIT-C screens within 9-15 months (February 1, 2008-September 30, 2014) were identified among PWH from the Veterans Aging Cohort Study (VACS). Initial and follow-up VACS Index 2.0 pairs obtained 0-270 days after initial and follow-up AUDIT-Cs, respectively, determined change in VACS Index 2.0, a composite HIV severity measure. Change in VACS Index 2.0 was regressed on AUDIT-C change scores (-12 to +12) adjusted for demographics, initial VACS Index 2.0, and days between VACS Index measures. RESULTS: Among 23,297 PWH (76,202 observations), most had no (51%) or low-level (38%) alcohol use initially. Most (54%) had no subsequent change; 21% increased and 24% decreased drinking. Initial VACS Index 2.0 scores ranged from 0 to 134, change scores ranged from -65 to +73, with average improvement of 0.76 points (SD 9.48). AUDIT-C change was associated with VACS Index 2.0 change (P < 0.001). Among those with stable alcohol use (AUDIT-C change ≤ │1│ point), VACS Index 2.0 improvements ranged 0.36-0.60 points. For those with maximum AUDIT-C increase (change from 0 to 12), VACS Index 2.0 worsened 3.74 points (95% CI: -4.71 to -2.78); for those with maximum AUDIT-C decrease (change from 12 to 0), VACS Index 2.0 changed minimally [-0.60 (95% CI: -1.43 to 0.23)]. CONCLUSIONS: In this national sample, improvement in HIV severity was generally greatest among those with stable alcohol use (primarily those with no use).

12.
Artigo em Inglês | MEDLINE | ID: mdl-30963773

RESUMO

Little is known about longitudinal change in physical functioning of older African American/Black and White HIV-infected persons. We examined up to 10 years of data on African American (N = 1,157) and White (N = 400) men with HIV infection and comparable HIV-negative men (n = 1,137 and 530, respectively), age 50-91 years from the Veterans Aging Cohort Study Survey sample. Physical functioning was assessed using the SF-12 (12-Item Short Form Health Survey) physical component summary (PCS) score. Mixed-effects models examined association of demographics, health conditions, health behaviors, and selected interactions with PCS score; HIV biomarkers were evaluated for HIV-infected persons. PCS scores were approximately one standard deviation below that of the general U.S. population of similar age. Across the four HIV/race groups, over time and through ages 65-75 years, PCS scores were maintained; differences were not clinically significant. PCS score was not associated with race or with interactions among age, race, and HIV status. CD4 and viral load counts of African American and White HIV-infected men were similar. Older age, low socioeconomic status, chronic health conditions and depression, lower body mass index, and smoking were associated with poorer PCS score in both groups. Exercising and, counterintuitively, being HIV infected were associated with better PCS score. Among these older African American and White male veterans, neither race nor HIV status was associated with PCS score, which remained relatively stable over time. Chronic disease, depression, and lack of exercise were associated with lower PCS score. To maintain independence in this population, attention should be paid to controlling chronic conditions, and emphasizing good health behaviors.

13.
Stat Med ; 38(13): 2428-2446, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30883859

RESUMO

Decisions about when to start or switch a therapy often depend on the frequency with which individuals are monitored or tested. For example, the optimal time to switch antiretroviral therapy depends on the frequency with which HIV-positive individuals have HIV RNA measured. This paper describes an approach to use observational data for the comparison of joint monitoring and treatment strategies and applies the method to a clinically relevant question in HIV research: when can monitoring frequency be decreased and when should individuals switch from a first-line treatment regimen to a new regimen? We outline the target trial that would compare the dynamic strategies of interest and then describe how to emulate it using data from HIV-positive individuals included in the HIV-CAUSAL Collaboration and the Centers for AIDS Research Network of Integrated Clinical Systems. When, as in our example, few individuals follow the dynamic strategies of interest over long periods of follow-up, we describe how to leverage an additional assumption: no direct effect of monitoring on the outcome of interest. We compare our results with and without the "no direct effect" assumption. We found little differences on survival and AIDS-free survival between strategies where monitoring frequency was decreased at a CD4 threshold of 350 cells/µl compared with 500 cells/µl and where treatment was switched at an HIV-RNA threshold of 1000 copies/ml compared with 200 copies/ml. The "no direct effect" assumption resulted in efficiency improvements for the risk difference estimates ranging from an 7- to 53-fold increase in the effective sample size.

14.
J Clin Invest ; 129(3): 1295-1313, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30776024

RESUMO

We identified 2 genes, histone deacetylase 1 (HDAC1) and HDAC2, contributing to the pathogenesis of proteinuric kidney diseases, the leading cause of end-stage kidney disease. mRNA expression profiling from proteinuric mouse glomeruli was linked to Connectivity Map databases, identifying HDAC1 and HDAC2 with the differentially expressed gene set reversible by HDAC inhibitors. In numerous progressive glomerular disease models, treatment with valproic acid (a class I HDAC inhibitor) or SAHA (a pan-HDAC inhibitor) mitigated the degree of proteinuria and glomerulosclerosis, leading to a striking increase in survival. Podocyte HDAC1 and HDAC2 activities were increased in mice podocytopathy models, and podocyte-associated Hdac1 and Hdac2 genetic ablation improved proteinuria and glomerulosclerosis. Podocyte early growth response 1 (EGR1) was increased in proteinuric patients and mice in an HDAC1- and HDAC2-dependent manner. Loss of EGR1 in mice reduced proteinuria and glomerulosclerosis. Longitudinal analysis of the multicenter Veterans Aging Cohort Study demonstrated a 30% reduction in mean annual loss of estimated glomerular filtration rate, and this effect was more pronounced in proteinuric patients receiving valproic acid. These results strongly suggest that inhibition of HDAC1 and HDAC2 activities may suppress the progression of human proteinuric kidney diseases through the regulation of EGR1.

15.
Med Care ; 57(4): 279-285, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30807449

RESUMO

BACKGROUND: Veterans with hepatitis C virus (HCV) infection may face geographic obstacles to obtaining treatment. OBJECTIVE: We studied the influence of region and rural versus urban residence on receipt of direct-acting antiretroviral (DAA) medications for HCV. SUBJECTS: Veterans receiving care within Veterans Affairs Healthcare System born between 1945 and 1965. RESEARCH DESIGN: This is a observational study using national electronic health record data. MEASURES: Receipt of DAAs was defined as ≥1 filled prescription from January 1, 2014 to December 31, 2016. Region (South, Northeast, Midwest, and West) and residence (urban, rural-micropolitan, small rural towns, and isolated rural towns) variables were created using residential zone improvement plan codes and rural-urban commuting area (RUCA) codes. Multivariable models were adjusted for age, race, sex, severity of liver disease, comorbidities, and prior treatment experience. RESULTS: Among 166,353 eligible patients 64,854 received, DAAs. Variation by rural-urban residence depended on region. In unadjusted analyses, receipt varied by rural-urban designations within Midwest, and West regions (P<0.05) but did not vary within the South (P=0.12). Southern rural small town had the lowest incidence of DAA receipt (40.1%), whereas the incidence was 52.9% in Midwestern isolated rural towns. In adjusted logistic analyses, compared with southern urban residents (the largest single group), southern rural small town residents had the lowest odds ratio, 0.85 (95% confidence interval, 0.75-0.93), and Midwestern residents from isolated and small rural towns had the highest odds (odds ratio, both 1.27) to receive treatment. CONCLUSIONS: Substantial geographic variation exists in receipt of curative HCV treatment. Efforts are needed to provide more equitable access to DAAs.


Assuntos
Antivirais/uso terapêutico , Hepacivirus/efeitos dos fármacos , Hepatite C/tratamento farmacológico , População Rural/estatística & dados numéricos , População Urbana/estatística & dados numéricos , Veteranos/estatística & dados numéricos , Idoso , Feminino , Humanos , Masculino , Estados Unidos , United States Department of Veterans Affairs
16.
AIDS ; 33(5): 903-912, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30649058

RESUMO

OBJECTIVE: Despite viral suppression and immune response on antiretroviral therapy, people with HIV infection experience excess mortality compared with uninfected individuals. The Veterans Aging Cohort Study (VACS) Index incorporates clinical biomarkers of general health with age, CD4 cell count, and HIV-1 RNA to discriminate mortality risk in a variety of HIV-positive populations. We asked whether additional biomarkers further enhance discrimination. DESIGN AND METHODS: Using patients from VACS for development and from the Antiretroviral Therapy Cohort Collaboration (ART-CC) for validation, we obtained laboratory values from a randomly selected visit from 2000 to 2014, at least 1 year after antiretroviral therapy initiation. Patients were followed for 5-year, all-cause mortality through September 2016. We fitted Cox models with established predictors and added new predictors based on model fit and Harrell's c-statistic. We converted all variables to continuous functional forms and selected the best model (VACS Index 2.0) for validation in ART-CC patients. We compared discrimination using c-statistics and Kaplan-Meier plots. RESULTS: Among 28 390 VACS patients and 12 109 ART-CC patients, 7293 and 722 died, respectively. Nadir CD4, CD8, and CD4 : CD8 ratio did not improve discrimination. Addition of albumin, white blood count, and BMI, improved c-statistics in VACS from 0.776 to 0.805 and in ART-CC from 0.800 to 0.831. Results were robust in all nine ART-CC cohorts, all lengths of follow-up and all subgroups. CONCLUSION: VACS Index 2.0, adding albumin, white blood count, and BMI to version 1.0 and using continuous variables, provides improved discrimination and is highly transportable to external settings.

17.
Alcohol Clin Exp Res ; 43(3): 522-530, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30620410

RESUMO

BACKGROUND: Current medications for alcohol use disorder (AUD) have limited efficacy and utilization. Some clinical trials have shown efficacy for gabapentin among treatment-seeking individuals. The impact of gabapentin on alcohol consumption in a more general sample remains unknown. METHODS: We identified patients prescribed gabapentin for ≥180 consecutive days for any clinical indication other than substance use treatment between 2009 and 2015 in the Veterans Aging Cohort Study. We propensity-score matched each gabapentin-exposed patient with up to 5 unexposed patients. Multivariable difference-in-difference (DiD) linear regression models estimated the differential change in Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) scores during follow-up between exposed and unexposed patients, by baseline level of alcohol consumption and daily gabapentin dose. Analyses were stratified by AUD history. Clinically meaningful changes were a priori considered a DiD ≥1 point. RESULTS: Among patients with AUD, AUDIT-C scores decreased 0.39 points (95% confidence interval [CI] 0.05, 0.73) more among exposed than unexposed patients (p < 0.03). Potentially clinically meaningful differences were observed among those with AUD and exposed to ≥1,500 mg/d (DiD 0.77, 95% CI 0.15, 1.38, p < 0.02). No statistically significant effects were found among patients with AUD at doses lower than 1,500 mg/d or baseline AUDIT-C ≥4. Among patients without AUD, we found no overall difference in changes in AUDIT-C scores, nor in analyses stratified by baseline level of alcohol consumption. CONCLUSIONS: Patients exposed to doses of gabapentin consistent with those used in clinical trials, particularly those with AUD, experienced a greater decrease in AUDIT-C scores than matched unexposed patients.

18.
JAMA Intern Med ; 179(3): 297-304, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30615036

RESUMO

Importance: Some opioids are known immunosuppressants; however, the association of prescribed opioids with clinically relevant immune-related outcomes is understudied, especially among people living with HIV. Objective: To assess the association of prescribed opioids with community-acquired pneumonia (CAP) by opioid properties and HIV status. Design, Setting, and Participants: This nested case-control study used data from patients in the Veterans Aging Cohort Study (VACS) from January 1, 2000, through December 31, 2012. Participants in VACS included patients living with and without HIV who received care in Veterans Health Administration (VA) medical centers across the United States. Patients with CAP requiring hospitalization (n = 4246) were matched 1:5 with control individuals without CAP (n = 21 146) by age, sex, race/ethnicity, length of observation, and HIV status. Data were analyzed from March 15, 2017, through August 8, 2018. Exposures: Prescribed opioid exposure during the 12 months before the index date was characterized by a composite variable based on timing (none, past, or current); low (<20 mg), medium (20-50 mg), or high (>50 mg) median morphine equivalent daily dose; and opioid immunosuppressive properties (yes vs unknown or no). Main Outcome and Measure: CAP requiring hospitalization based on VA and Centers for Medicare & Medicaid data. Results: Among the 25 392 VACS participants (98.9% male; mean [SD] age, 55 [10] years), current medium doses of opioids with unknown or no immunosuppressive properties (adjusted odds ratio [AOR], 1.35; 95% CI, 1.13-1.62) and immunosuppressive properties (AOR, 2.07; 95% CI, 1.50-2.86) and current high doses of opioids with unknown or no immunosuppressive properties (AOR, 2.07; 95% CI, 1.50-2.86) and immunosuppressive properties (AOR, 3.18; 95% CI, 2.44-4.14) were associated with the greatest CAP risk compared with no prescribed opioids or any past prescribed opioid with no immunosuppressive (AOR, 1.24; 95% CI, 1.09-1.40) and immunosuppressive properties (AOR, 1.42; 95% CI, 1.21-1.67), especially with current receipt of immunosuppressive opioids. In stratified analyses, CAP risk was consistently greater among people living with HIV with current prescribed opioids, especially when prescribed immunosuppressive opioids (eg, AORs for current immunosuppressive opioids with medium dose, 1.76 [95% CI, 1.20-2.57] vs 2.33 [95% CI, 1.60-3.40]). Conclusions and Relevance: Prescribed opioids, especially higher-dose and immunosuppressive opioids, are associated with increased CAP risk among persons with and without HIV.

19.
Alcohol Clin Exp Res ; 43(3): 465-472, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30592535

RESUMO

BACKGROUND: A variety of measures have been developed to screen for hazardous or harmful drinking. The Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) is one of the screening measures recommended by the U.S. Preventive Services Task Force. Annual administration of the AUDIT-C to all primary care patients is required by the U.S. Veterans Affairs Health System. The availability of data from the repeated administration of this instrument over time in a large patient population provides an opportunity to evaluate the utility of the AUDIT-C for identifying distinct drinking groups. METHODS: Using data from the Million Veteran Program cohort, we modeled group-based drinking trajectories using 2,833,189 AUDIT-C scores from 495,178 Veterans across an average 6-year time period. We also calculated patients' age-adjusted mean AUDIT-C scores to compare to the drinking trajectories. Finally, we extracted data on selected clinical diagnoses from the electronic health record and assessed their associations with the drinking trajectories. RESULTS: Of the trajectory models, the 4-group model demonstrated the best fit to the data. AUDIT-C trajectories were highly correlated with the age-adjusted mean AUDIT-C scores (rs = 0.94). Those with an alcohol use disorder diagnosis had 10 times the odds of being in the highest trajectory group (consistently hazardous/harmful) compared to the lowest drinking trajectory group (infrequent). Those with hepatitis C, posttraumatic stress disorder, liver cirrhosis, and delirium had 10, 7, 21, and 34%, respectively, higher odds of being classified in the highest drinking trajectory group versus the lowest drinking trajectory group. CONCLUSIONS: Trajectories and age-adjusted mean scores are potentially useful approaches to optimize the information provided by the AUDIT-C. In contrast to trajectories, age-adjusted mean AUDIT-C scores also have clinical relevance for real-time identification of individuals for whom an intervention may be warranted.

20.
J Acquir Immune Defic Syndr ; 80(3): 292-300, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30531492

RESUMO

BACKGROUND: An increasing number of HIV-positive individuals now start antiretroviral therapy (ART) with high CD4 cell counts. We investigated whether this makes restoration of CD4 and CD8 cell counts and the CD4:CD8 ratio during virologically suppressive ART to median levels seen in HIV-uninfected individuals more likely and whether restoration depends on gender, age, and other individual characteristics. METHODS: We determined median and quartile reference values for CD4 and CD8 cell counts and their ratio using cross-sectional data from 2309 HIV-negative individuals. We used longitudinal measurements of 60,997 HIV-positive individuals from the Antiretroviral Therapy Cohort Collaboration in linear mixed-effects models. RESULTS: When baseline CD4 cell counts were higher, higher long-term CD4 cell counts and CD4:CD8 ratios were reached. Highest long-term CD4 cell counts were observed in middle-aged individuals. During the first 2 years, median CD8 cell counts converged toward median reference values. However, changes were small thereafter and long-term CD8 cell count levels were higher than median reference values. Median 8-year CD8 cell counts were higher when ART was started with <250 CD4 cells/mm. Median CD4:CD8 trajectories did not reach median reference values, even when ART was started at 500 cells/mm. DISCUSSION: Starting ART with a CD4 cell count of ≥500 cells/mm makes reaching median reference CD4 cell counts more likely. However, median CD4:CD8 ratio trajectories remained below the median levels of HIV-negative individuals because of persisting high CD8 cell counts. To what extent these subnormal immunological responses affect specific clinical endpoints requires further investigation.

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