Impact of Potential Case Misclassification by Administrative Diagnostic Codes on Outcome Assessment of Observational Study for People Who Inject Drugs.

Introduction: Initiation of medications for opioid use disorder (MOUD) within the hospital setting may improve outcomes for people who inject drugs (PWID) hospitalized because of an infection. Many studies used International Classification of Diseases (ICD) codes to identify PWID, although these may be misclassified and thus, inaccurate. We hypothesized that bias from misclassification of PWID using ICD codes may impact analyses of MOUD outcomes. Methods: We analyzed a cohort of 36 868 cases of patients diagnosed with Staphylococcus aureus bacteremia at 124 US Veterans Health Administration hospitals between 2003 and 2014. To identify PWID, we implemented an ICD code-based algorithm and a natural language processing (NLP) algorithm for classification of admission notes. We analyzed outcomes of prescribing MOUD as an inpatient using both approaches. Our primary outcome was 365-day all-cause mortality. We fit mixed-effects Cox regression models with receipt or not of MOUD during the index hospitalization as the primary predictor and 365-day mortality as the outcome. Results: NLP identified 2389 cases as PWID, whereas ICD codes identified 6804 cases as PWID. In the cohort identified by NLP, receipt of inpatient MOUD was associated with a protective effect on 365-day survival (adjusted hazard ratio, 0.48; 95% confidence interval, .29-.81; P < .01) compared with those not receiving MOUD. There was no significant effect of MOUD receipt in the cohort identified by ICD codes (adjusted hazard ratio, 1.00; 95% confidence interval, .77-1.30; P = .99). Conclusions: MOUD was protective of all-cause mortality when NLP was used to identify PWID, but not significant when ICD codes were used to identify the analytic subjects.

Alcohol Use and Sustained Virologic Response to Hepatitis C Virus Direct-Acting Antiviral Therapy.

Importance: Some payers and clinicians require alcohol abstinence to receive direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection. Objective: To evaluate whether alcohol use at DAA treatment initiation is associated with decreased likelihood of sustained virologic response (SVR). Design, Setting, and Participants: This retrospective cohort study used electronic health records from the US Department of Veterans Affairs (VA), the largest integrated national health care system that provides unrestricted access to HCV treatment. Participants included all patients born between 1945 and 1965 who were dispensed DAA therapy between January 1, 2014, and June 30, 2018. Data analysis was completed in November 2020 with updated sensitivity analyses performed in 2023. Exposure: Alcohol use categories were generated using responses to the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) questionnaire and International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnoses for alcohol use disorder (AUD): abstinent without history of AUD, abstinent with history of AUD, lower-risk consumption, moderate-risk consumption, and high-risk consumption or AUD. Main Outcomes and Measures: The primary outcome was SVR, which was defined as undetectable HCV RNA for 12 weeks or longer after completion of DAA therapy. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% CIs of SVR associated with alcohol category. Results: Among 69 229 patients who initiated DAA therapy (mean [SD] age, 62.6 [4.5] years; 67 150 men [97.0%]; 34 655 non-Hispanic White individuals [50.1%]; 28 094 non-Hispanic Black individuals [40.6%]; 58 477 individuals [84.5%] with HCV genotype 1), 65 355 (94.4%) achieved SVR. A total of 32 290 individuals (46.6%) were abstinent without AUD, 9192 (13.3%) were abstinent with AUD, 13 415 (19.4%) had lower-risk consumption, 3117 (4.5%) had moderate-risk consumption, and 11 215 (16.2%) had high-risk consumption or AUD. After adjustment for potential confounding variables, there was no difference in SVR across alcohol use categories, even for patients with high-risk consumption or AUD (OR, 0.95; 95% CI, 0.85-1.07). There was no evidence of interaction by stage of hepatic fibrosis measured by fibrosis-4 score (P for interaction = .30). Conclusions and Relevance: In this cohort study, alcohol use and AUD were not associated with lower odds of SVR. Restricting access to DAA therapy according to alcohol use creates an unnecessary barrier to patients and challenges HCV elimination goals.

Effect of Androgen Suppression on Clinical Outcomes in Hospitalized Men With COVID-19: The HITCH Randomized Clinical Trial.

Importance: SARS-CoV-2 entry requires the TMPRSS2 cell surface protease. Antiandrogen therapies reduce expression of TMPRSS2. Objective: To determine if temporary androgen suppression induced by degarelix improves clinical outcomes of inpatients hospitalized with COVID-19. Design, Setting, and Participants: The Hormonal Intervention for the Treatment in Veterans With COVID-19 Requiring Hospitalization (HITCH) phase 2, placebo-controlled, double-blind, randomized clinical trial compared efficacy of degarelix plus standard care vs placebo plus standard care on clinical outcomes in men hospitalized with COVID-19 but not requiring invasive mechanical ventilation. Inpatients were enrolled at 14 Department of Veterans Affairs hospitals from July 22, 2020, to April 8, 2021. Data were analyzed from August 9 to October 15, 2021. Interventions: Patients stratified by age, history of hypertension, and disease severity were centrally randomized 2:1 to degarelix, (1-time subcutaneous dose of 240 mg) or a saline placebo. Standard care included but was not limited to supplemental oxygen, antibiotics, vasopressor support, peritoneal dialysis or hemodialysis, intravenous fluids, remdesivir, convalescent plasma, and dexamethasone. Main Outcomes and Measures: The composite primary end point was mortality, ongoing need for hospitalization, or requirement for mechanical ventilation at day 15 after randomization. Secondary end points were time to clinical improvement, inpatient mortality, length of hospitalization, duration of mechanical ventilation, time to achieve a temperature within reference range, maximum severity of COVID-19, and the composite end point at 30 days. Results: The trial was stopped for futility after the planned interim analysis, at which time there were 96 evaluable patients, including 62 patients randomized to the degarelix group and 34 patients in the placebo group, out of 198 initially planned. The median (range) age was 70.5 (48-85) years. Common comorbidities included chronic obstructive pulmonary disorder (15 patients [15.6%]), hypertension (75 patients [78.1%]), cardiovascular disease (27 patients [28.1%]), asthma (12 patients [12.5%]), diabetes (49 patients [51.0%]), and chronic respiratory failure requiring supplemental oxygen at baseline prior to COVID-19 (9 patients [9.4%]). For the primary end point, there was no significant difference between the degarelix and placebo groups (19 patients [30.6%] vs 9 patients [26.5%]; P = .67). Similarly, no differences were observed between degarelix and placebo groups in any secondary end points, including inpatient mortality (11 patients [17.7%] vs 6 patients [17.6%]) or all-cause mortality (11 patients [17.7%] vs 7 patents [20.6%]). There were no differences between degarelix and placebo groups in the overall rates of adverse events (13 patients [21.0%] vs 8 patients [23.5%) and serious adverse events (19 patients [30.6%] vs 13 patients [32.4%]), nor unexpected safety concerns. Conclusions and Relevance: In this randomized clinical trial of androgen suppression vs placebo and usual care for men hospitalized with COVID-19, degarelix did not result in amelioration of COVID-19 severity. Trial Registration: ClinicalTrials.gov Identifier: NCT04397718.

Delayed presentation of HIV among older individuals: a growing problem.

Late presentation for care is a major impediment to the prevention and effective treatment of HIV infection. Older individuals are at increased risk of late presentation, represent a growing proportion of people with late presentation, and might require interventions tailored to their age group. We provide a summary of the literature published globally between 2016-21 (reporting data from 1984-2018) and quantify the association of age with delayed presentation. Using the most common definitions of late presentation and older age from these earlier studies, we update this work with data from the International Epidemiology Databases to Evaluate AIDS (IeDEA) consortium, focusing on data from 2000-19, encompassing four continents. Finally, we consider how late presentation among older individuals might be more effectively addressed as electronic medical records become widely adopted.

Prostate Cancer Screening and Incidence among Aging Persons Living with HIV.

PURPOSE: The risk of prostate cancer among persons living with human immunodeficiency virus (PWH) is not well understood and may be obscured by different opportunities for detection. MATERIALS AND METHODS: We identified 123,472 (37,819 PWH and 85,653 comparators) men enrolled in the Veterans Aging Cohort Study, a prospective national cohort of PWH and demographically matched, uninfected comparators in 2000-2015. We calculated rates of prostate specific antigen (PSA) testing by human immunodeficiency virus (HIV) status and fit multivariable Poisson models comparing the rates of PSA testing, prostate biopsy, and cancer incidence. RESULTS: The mean age at enrollment was 52 years. Rates of PSA testing were lower in PWH versus uninfected comparators (0.58 versus 0.63 tests per person-year). Adjusted rates of PSA screening and prostate biopsy were lower among PWH (incidence rate ratio [IRR] 0.87, 95% CI 0.75-0.84 and IRR 0.79 95% CI 0.74-0.83, respectively). The crude IRR for prostate cancer was lower in PWH versus controls (IRR 0.90, 95% CI 0.83-0.97). However, in a multivariable model adjusting for PSA testing, cancer incidence was similar by HIV status (IRR=0.93, 95% CI 0.86-1.01, p=0.08). Among patients who received a prostate biopsy, incidence of prostate cancer did not differ significantly by HIV status (IRR 1.06, 95% CI 0.98-1.15, p=0.15). Among incident cancers, there were significant differences in the distributions of Gleason grade (p=0.05), but not cancer stage (p=0.14) by HIV status. CONCLUSIONS: When accounting for less PSA testing among PWH, the incidence of prostate cancer was similar by HIV status. These findings suggest that less screening contributed to lower observed incidence of prostate cancer in PWH.

Hormonal intervention for the treatment of veterans with COVID-19 requiring hospitalization (HITCH): a multicenter, phase 2 randomized controlled trial of best supportive care vs best supportive care plus degarelix: study protocol for a randomized controlled trial.

BACKGROUND: Therapeutic targeting of host-cell factors required for SARS-CoV-2 entry is an alternative strategy to ameliorate COVID-19 severity. SARS-CoV-2 entry into lung epithelium requires the TMPRSS2 cell surface protease. Pre-clinical and correlative data in humans suggest that anti-androgenic therapies can reduce the expression of TMPRSS2 on lung epithelium. Accordingly, we hypothesize that therapeutic targeting of androgen receptor signaling via degarelix, a luteinizing hormone-releasing hormone (LHRH) antagonist, will suppress COVID-19 infection and ameliorate symptom severity. METHODS: This is a randomized phase 2, placebo-controlled, double-blind clinical trial in 198 patients to compare efficacy of degarelix plus best supportive care versus placebo plus best supportive care on improving the clinical outcomes of male Veterans who have been hospitalized due to COVID-19. Enrolled patients must have documented infection with SARS-CoV-2 based on a positive reverse transcriptase polymerase chain reaction result performed on a nasopharyngeal swab and have a severity of illness of level 3-5 (hospitalized but not requiring invasive mechanical ventilation). Patients stratified by age, history of hypertension, and severity are centrally randomized 2:1 (degarelix: placebo). The composite primary endpoint is mortality, ongoing need for hospitalization, or requirement for mechanical ventilation at 15 after randomization. Important secondary endpoints include time to clinical improvement, inpatient mortality, length of hospitalization, duration of mechanical ventilation, time to achieve a normal temperature, and the maximum severity of COVID-19 illness. Exploratory analyses aim to assess the association of cytokines, viral load, and various comorbidities with outcome. In addition, TMPRSS2 expression in target tissue and development of anti-viral antibodies will also be investigated. DISCUSSION: In this trial, we repurpose the FDA approved LHRH antagonist degarelix, commonly used for prostate cancer, to suppress TMPRSS2, a host cell surface protease required for SARS-CoV-2 cell entry. The objective is to determine if temporary androgen suppression with a single dose of degarelix improves the clinical outcomes of patients hospitalized due to COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov NCT04397718. Registered on May 21, 2020.

Conditional reflex to urine culture: Evaluation of a diagnostic stewardship intervention within the Veterans' Affairs and Centers for Disease Control and Prevention Practice-Based Research Network.

OBJECTIVE: In the absence of pyuria, positive urine cultures are unlikely to represent infection. Conditional urine reflex culture policies have the potential to limit unnecessary urine culturing. We evaluated the impact of this diagnostic stewardship intervention. DESIGN: We conducted a retrospective, quasi-experimental (nonrandomized) study, with interrupted time series, from August 2013 to January 2018 to examine rates of urine cultures before versus after the policy intervention. We compared 3 intervention sites to 3 control sites in an aggregated series using segmented negative binomial regression. SETTING: The study included 6 acute-care hospitals within the Veterans' Health Administration across the United States. PARTICIPANTS: Adult patients with at least 1 urinalysis ordered during acute-care admission, excluding pregnant patients or those undergoing urological procedures, were included. METHODS: At the intervention sites, urine cultures were performed if a preceding urinalysis met prespecified criteria. No such restrictions occurred at the control sites. The primary outcome was the rate of urine cultures performed per 1,000 patient days. The safety outcome was the rate of gram-negative bloodstream infection per 1,000 patient days. RESULTS: The study included 224,573 urine cultures from 50,901 admissions in 24,759 unique patients. Among the intervention sites, the overall average number of urine cultures performed did not significantly decrease relative to the preintervention period (5.9% decrease; P = 0.8) but did decrease by 21% relative to control sites (P < .01). We detected no significant difference in the rates of gram-negative bloodstream infection among intervention or control sites (P = .49). CONCLUSIONS: Conditional urine reflex culture policies were associated with a decrease in urine culturing without a change in the incidence of gram-negative bloodstream infection.

Antibiotic Stewardship Implementation and Antibiotic Use at Hospitals With and Without On-site Infectious Disease Specialists.

BACKGROUND: Many US hospitals lack infectious disease (ID) specialists, which may hinder antibiotic stewardship efforts. We sought to compare patient-level antibiotic exposure at Veterans Health Administration (VHA) hospitals with and without an on-site ID specialist, defined as an ID physician and/or ID pharmacist. METHODS: This retrospective VHA cohort included all acute-care patient admissions during 2016. A mandatory survey was used to identify hospitals' antibiotic stewardship processes and their access to an on-site ID specialist. Antibiotic use was quantified as days of therapy per days present and categorized based on National Healthcare Safety Network definitions. A negative binomial regression model with risk adjustment was used to determine the association between presence of an on-site ID specialist and antibiotic use at the level of patient admissions. RESULTS: Eighteen of 122 (14.8%) hospitals lacked an on-site ID specialist; there were 525 451 (95.8%) admissions at ID hospitals and 23 007 (4.2%) at non-ID sites. In the adjusted analysis, presence of an ID specialist was associated with lower total inpatient antibacterial use (odds ratio, 0.92; 95% confidence interval, .85-.99). Presence of an ID specialist was also associated with lower use of broad-spectrum antibacterials (0.61; .54-.70) and higher narrow-spectrum ß-lactam use (1.43; 1.22-1.67). Total antibacterial exposure (inpatient plus postdischarge) was lower among patients at ID versus non-ID sites (0.92; .86-.99). CONCLUSIONS: Patients at hospitals with an ID specialist received antibiotics in a way more consistent with stewardship principles. The presence of an ID specialist may be important to effective antibiotic stewardship.

The Impact of Rapid Species Identification on Management of Bloodstream Infections: What's in a Name?

Bloodstream infections are a leading cause of morbidity and mortality. Molecular rapid diagnostic tests (mRDTs) are transforming care for patients with bloodstream infection by providing the opportunity to dramatically shorten times to effective therapy and speeding de-escalation of overly broad empiric therapy. However, because of the novelty of these tests which provide information regarding microbial identification and whether specific antibiotic-resistance mutations were detected, many front-line providers still delay final decisions until complete phenotypic susceptibility results are available several days later. Thus the benefits of mRDTs have been largely limited to circumstances where antimicrobial stewardship programs closely monitor these tests and intervene as soon as the results are available. We searched PubMed and Google Scholar for articles published from 1980 to 2019 using the terms antibiotic, antifungal, bacteremia, bloodstream infection, candidemia, candidiasis, children, coagulase negative staphylococcus, consultation, contamination, costs, echocardiogram, endocarditis, enterobacteriaceae, enterococcus, Gram-negative, guidelines, IDSA, immunocompromised, infectious disease or ID, lumbar puncture, meningitis, mortality, MRSA, MSSA, neonatal, outcomes, pediatric, pneumococcal, polymicrobial, Pseudomonas, rapid diagnostic testing, resistance, risk factors, sepsis, Staphylococcus aureus, stewardship, streptococcus, and treatment. With the data from this search, we aim to provide guidance to front-line providers regarding the interpretation and immediate actions to be taken in response to the identification of common bloodstream pathogens by mRDTs. In addition to antimicrobial therapy, additional diagnostic or therapeutic interventions are recommended for particular organisms and clinical settings to either determine the extent of infection or control its source. Pediatric perspectives are offered for those bloodstream pathogens for which management differs from that in adults.

A Telephone and Mail Outreach Program Successfully Increases Uptake of Hepatocellular Carcinoma Surveillance.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Society guidelines recommend surveillance with abdominal ultrasound with or without serum alpha-fetoprotein every 6 months for adults at increased risk of developing HCC. However, adherence is often suboptimal. We assessed the feasibility of a coordinated telephone outreach program for unscreened patients with cirrhosis within the Veteran's Affairs (VA) health care system. Using a patient care dashboard of advanced chronic liver disease in the VA Greater Los Angeles Healthcare System, we identified veterans with a diagnosis of cirrhosis, a platelet count ≤ 150,000/uL, and no documented HCC surveillance in the previous 8 months. Eligible veterans received a telephone call from a patient navigator to describe the risks and benefits of HCC surveillance. Orders for an abdominal ultrasound and alpha-fetoprotein were placed for veterans who agreed to surveillance. Veterans who were not reached by telephone received an informational letter by mail to encourage participation. Of the 129 veterans who met the eligibility criteria, most were male (96.9%). The most common etiology for cirrhosis was hepatitis C (64.3%), and most of the patients had compensated cirrhosis (68.2%). The patient navigators reached 32.5% of patients by phone. Patients in each group were similar across clinical and demographic characteristics. Patients who were called were more likely to undergo surveillance (adjusted odds ratio = 2.56, 95% confidence interval: 1.03-6.33). Most of the patients (72.1%) completed abdominal imaging when reached by phone. Conclusion: Targeted outreach increased uptake of HCC surveillance among patients with cirrhosis in a large, integrated, VA health care system.

Establishment of a COVID-19 Recovery Unit in a Veterans Affairs Post-Acute Facility.

Coronavirus disease 2019 (COVID-19) is now an epidemic of global proportion, with major adverse impacts on older adults, persons with chronic diseases, and especially residents of long-term care facilities. This health catastrophe has challenged healthcare facilities' capacity to deliver care to not only COVID-19 patients but all patients who need hospital care. We report on a novel approach of utilizing long-term care beds at a Department of Veterans Affairs healthcare facility for managing recovering COVID-19 patients. J Am Geriatr Soc 68:2163-2166, 2020.

Universal and Serial Laboratory Testing for SARS-CoV-2 at a Long-Term Care Skilled Nursing Facility for Veterans - Los Angeles, California, 2020.

On March 28, 2020, two residents of a long-term care skilled nursing facility (SNF) at the Veterans Affairs Greater Los Angeles Healthcare System (VAGLAHS) had positive test results for SARS-CoV-2, the cause of coronavirus disease 2019 (COVID-19), by reverse transcription-polymerase chain reaction (RT-PCR) testing of nasopharyngeal specimens collected on March 26 and March 27. During March 29-April 23, all SNF residents, regardless of symptoms, underwent serial (approximately weekly) nasopharyngeal SARS-CoV-2 RT-PCR testing, and positive results were communicated to the county health department. All SNF clinical and nonclinical staff members were also screened for SARS-CoV-2 by RT-PCR during March 29-April 10. Nineteen of 99 (19%) residents and eight of 136 (6%) staff members had positive test results for SARS-CoV-2 during March 28-April 10; no further resident cases were identified on subsequent testing on April 13, April 22, and April 23. Fourteen of the 19 residents with COVID-19 were asymptomatic at the time of testing. Among these residents, eight developed symptoms 1-5 days after specimen collection and were later classified as presymptomatic; one of these patients died. This report describes an outbreak of COVID-19 in an SNF, with case identification accomplished by implementing several rounds of RT-PCR testing, permitting rapid isolation of both symptomatic and asymptomatic residents with COVID-19. The outbreak was successfully contained following implementation of this strategy.

Long term surgical outcomes for infective endocarditis in people who inject drugs: a systematic review and meta-analysis.

BACKGROUND: In recent years, the number of infective endocarditis (IE) cases associated with injection drug use has increased. Clinical guidelines suggest deferring surgery for IE in people who inject drugs (PWID) due to a concern for worse outcomes in comparison to non-injectors (non-PWID). We performed a systematic review and meta-analysis of long-term outcomes in PWID who underwent cardiac surgery and compared these outcomes to non-PWID. METHODS: We systematically searched for studies reported between 1965 and 2018. We used an algorithm to estimate individual patient data (eIPD) from Kaplan-Meier (KM) curves and combined it with published individual patient data (IPD) to analyze long-term outcomes after cardiac surgery for IE in PWID. Our primary outcome was survival. Secondary outcomes were reoperation and mortality at 30-days, one-, five-, and 10-years. Random effects Cox regression was used for estimating survival. RESULTS: We included 27 studies in the systematic review and 19 provided data (KM or IPD) for the meta-analysis. PWID were younger and more likely to have S. aureus than non-PWID. Survival at 30-days, one-, five-, and 10-years was 94.3, 81.0, 62.1, and 56.6% in PWID, respectively; and 96.4, 85.0, 70.3, and 63.4% in non-PWID. PWID had 47% greater hazard of death (HR 1.47, 95% CI, 1.05-2.05) and more than twice the hazard of reoperation (HR 2.37, 95% CI, 1.25-4.50) than non-PWID. CONCLUSION: PWID had shorter survival that non-PWID. Implementing evidence-based interventions and testing new modalities are urgently needed to improve outcomes in PWID after cardiac surgery.

Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios as Prognostic Inflammatory Biomarkers in Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV), and HIV/HCV Coinfection.

BACKGROUND: Inflammation in human immunodeficiency virus (HIV)-infected patients is associated with poorer health outcomes. Whether inflammation as measured by the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) adds information to existing prognostic indices is not known. METHODS: We analyzed data from 2000 to 2012 in the Veterans Aging Cohort Study (VACS), overall and stratified by HIV/hepatitis C virus status (n = 89 786). We randomly selected a visit date at which all laboratory values of interest were available within 180 days; participants with HIV received at least 1 year of antiretroviral therapy. We followed patients for (1) mortality and (2) hepatic decompensation (HD) and analyzed associations using Cox regression, adjusted for a validated mortality risk index (VACS Index 2.0). In VACS Biomarker Cohort, we considered correlation with biomarkers of inflammation: interleukin-6, D-dimer, and soluble CD-14. RESULTS: Neutrophil-to-lymphocyte ratio and PLR demonstrated strong unadjusted associations with mortality (P < .0001) and HD (P < .0001) and were weakly correlated with other inflammatory biomarkers. Although NLR remained statistically independent for mortality, as did PLR for HD, the addition of NLR and PLR to the VACS Index 2.0 did not result in significant improvement in discrimination compared with VACS Index 2.0 alone for mortality (C-statistic 0.767 vs 0.758) or for HD (C-statistic 0.805 vs 0.801). CONCLUSIONS: Neutrophil-to-lymphocyte ratio and PLR were strongly associated with mortality and HD and weakly correlated with inflammatory biomarkers. However, most of their association was explained by VACS Index 2.0. Addition of NLR and PLR to VACS 2.0 did not substantially improve discrimination for either outcome.

Comparison of the prevalence, severity, and risk factors for hepatic steatosis in HIV-infected and uninfected people.

BACKGROUND: Hepatic steatosis is prevalent in Western countries, but few studies have evaluated whether the frequency and severity of steatosis are greater in the setting of HIV infection. We compared the prevalence and severity of hepatic steatosis between HIV-infected (HIV+) and uninfected persons and identified factors associated with greater steatosis severity within both groups. METHODS: We performed a cross-sectional study among participants without cardiovascular disease who participated in a substudy of the Veterans Aging Cohort Study. Hepatic steatosis was defined by noncontrast computed tomography (CT) liver-to-spleen (L/S) attenuation ratio < 1.0. Multivariable linear regression was used to: 1) evaluate the association between HIV infection and severity of hepatic steatosis, as measured by absolute liver attenuation, and 2) identify factors associated with greater severity of steatosis, by HIV status. RESULTS: Among 268 participants (median age, 55 years; 99% male; 79% black; 23% obese; 64% HIV+ [91% on antiretroviral therapy]), the overall prevalence of steatosis was 7.8% and was similar between HIV+ and uninfected individuals (13 [7.6%] versus 8 [8.2%], respectively; p = 0.85). Participants with HIV, the majority of whom received antiretroviral therapy, had a higher mean absolute liver attenuation (mean difference, 5.68 Hounsfield units; p < 0.001), correlating with lesser hepatic steatosis severity, compared to uninfected participants. After adjusting for covariates, only advanced hepatic fibrosis was associated with greater severity of steatosis in HIV+ persons (p = 0.03) and uninfected individuals (p < 0.001). CONCLUSIONS: In this sample of participants without cardiovascular disease, the prevalence of hepatic steatosis by noncontrast abdominal CT was not different by HIV status. Increasing severity of steatosis was independently associated with advanced hepatic fibrosis in both groups.

Corticosteroids in the Management of Severe Coccidioidomycosis.

BACKGROUND: There is limited data suggesting that recovery from severe pulmonary infection with Coccidioides may be hastened by the addition of systemic corticosteroids. METHODS: We present a case report of 2 patients with persistent and progressive coccidioidomycosis who demonstrated a dramatic response to adjunctive corticosteroid therapy. RESULTS: Both patients had Coccidioides immitis cultured from respiratory samples. One was a 69-year-old man who had been treated with combination fluconazole and liposomal amphotericin for over 6 weeks, with persistent fever and pneumonia. The other was a 61-year-old man treated with fluconazole and then amphotericin for 3 weeks, with progression to acute respiratory distress syndrome and shock. Both received short courses of intravenous methylprednisolone and recovered to be discharged home. CONCLUSIONS: As opposed to associated hypersensitivity, corticosteroid treatment in these cases was directed at modulating the ongoing destructive effects of unchecked inflammation. Rapid improvement was noted in both cases and raises the possibility that the addition of systemic corticosteroids may hasten recovery in patients with severe coccidioidomycosis.

In Data We Trust? Comparison of Electronic Versus Manual Abstraction of Antimicrobial Prescribing Quality Metrics for Hospitalized Veterans With Pneumonia.

BACKGROUND: Electronic health records provide the opportunity to assess system-wide quality measures. Veterans Affairs Pharmacy Benefits Management Center for Medication Safety uses medication use evaluation (MUE) through manual review of the electronic health records. OBJECTIVE: To compare an electronic MUE approach versus human/manual review for extraction of antibiotic use (choice and duration) and severity metrics. RESEARCH DESIGN: Retrospective. SUBJECTS: Hospitalizations for uncomplicated pneumonia occurring during 2013 at 30 Veterans Affairs facilities. MEASURES: We compared summary statistics, individual hospitalization-level agreement, facility-level consistency, and patterns of variation between electronic and manual MUE for initial severity, antibiotic choice, daily clinical stability, and antibiotic duration. RESULTS: Among 2004 hospitalizations, electronic and manual abstraction methods showed high individual hospitalization-level agreement for initial severity measures (agreement=86%-98%, κ=0.5-0.82), antibiotic choice (agreement=89%-100%, κ=0.70-0.94), and facility-level consistency for empiric antibiotic choice (anti-MRSA r=0.97, P<0.001; antipseudomonal r=0.95, P<0.001) and therapy duration (r=0.77, P<0.001) but lower facility-level consistency for days to clinical stability (r=0.52, P=0.006) or excessive duration of therapy (r=0.55, P=0.005). Both methods identified widespread facility-level variation in antibiotic choice, but we found additional variation in manual estimation of excessive antibiotic duration and initial illness severity. CONCLUSIONS: Electronic and manual MUE agreed well for illness severity, antibiotic choice, and duration of therapy in pneumonia at both the individual and facility levels. Manual MUE showed additional reviewer-level variation in estimation of initial illness severity and excessive antibiotic use. Electronic MUE allows for reliable, scalable tracking of national patterns of antimicrobial use, enabling the examination of system-wide interventions to improve quality.

HIV and Age Do Not Synergistically Affect Age-Related T-Cell Markers.

INTRODUCTION: Despite major progress in controlling HIV disease through antiretroviral therapy, changes in immune phenotype and function persist in individuals with chronic HIV, raising questions about accelerated aging of the immune system. METHODS: We conducted a cross-sectional study (2005-2007) of HIV-infected (n = 111) and uninfected (n = 114) men from the Veterans Aging Cohort Study. All HIV-infected subjects were on antiretroviral therapy with VL <400 copies/mL for at least 3 years. T-cell markers were examined using flow cytometry. We evaluated the impact of HIV serostatus and age on T-cell phenotypes (expressed as percentages of the total CD4 and CD8 T-cell population) using multivariate linear regression, adjusted for smoking, alcohol, and race/ethnicity. We tested for interactions between HIV and age by including interaction terms. RESULTS: Among both HIV-infected and uninfected subjects, increasing age was associated with a decreased proportion of naive CD4 T cells (P = 0.014) and CD8 T cells (P < 0.0001). Both HIV infection and increasing age were associated with higher proportions of effector memory CD4 T cells (P < 0.0001 for HIV; P = 0.04 for age) and CD8 T cells (P = 0.0001 for HIV; P = 0.0004 for age). HIV infection, but not age, was associated with a higher proportion of activated CD8 T cells (P < 0.0001). For all T-cell subsets tested, there were no significant interactions between HIV infection and age. CONCLUSIONS: Age and HIV status independently altered the immune system, but we found no conclusive evidence that HIV infection and advancing age synergistically result in accelerated changes in age-associated T-cell markers among virally suppressed individuals.

HIV and Obesity Comorbidity Increase Interleukin 6 but Not Soluble CD14 or D-Dimer.

OBJECTIVES: Obesity prevalence among people living with HIV (HIV+) is rising. HIV and obesity are proinflammatory states, but their combined effect on inflammation (measured by interleukin 6, IL-6), altered coagulation (D-dimer), and monocyte activation (soluble CD14, sCD14) is unknown. We hypothesized inflammation increases when obesity and HIV infection co-occur. METHODS: The Veterans Aging Cohort Study survey cohort is a prospective, observational study of predominantly male HIV+ veterans and veterans uninfected with HIV; a subset provided blood samples. Inclusion criteria for this analysis were body mass index ≥ 18.5 kg/m and biomarker measurement. Dependent variables were IL-6, sCD14, and D-dimer quartiles. Obesity/HIV status was the primary predictor. Unadjusted and adjusted logistic regression models were constructed. RESULTS: Data were analyzed for 1477 HIV+ and 823 uninfected participants. Unadjusted median IL-6 levels were significantly higher and sCD14 levels significantly lower in obese/HIV+ compared with nonobese/uninfected (P <0.01 for both). In adjusted analyses, the odds ratio for increased IL-6 in obese/HIV+ patients was 1.76 (95% confidence interval: 1.18 to 2.47) compared with nonobese/uninfected, and obesity/HIV+ remained associated with lower odds of elevated sCD14. We did not detect a synergistic association of co-occurring HIV and obesity on IL-6 or sCD14 elevation. D-dimer levels did not differ significantly between body mass index/HIV status groups. CONCLUSIONS: HIV-obesity comorbidity is associated with elevated IL-6, decreases in sCD14, and no significant difference in D-dimer. These findings are clinically significant, as previous studies associated these biomarkers with mortality. Future studies should assess whether other biomarkers show similar trends and potential mechanisms for unanticipated sCD14 and D-dimer findings.