Search

A Hepatitis C (HCV) e-Consult Direct-To-Treatment (DTT) program managed by midlevel providers was developed at the Veteran Affairs Greater Los Angeles Healthcare System (VAGLAHS) which provided remote referral and, in some, remote management of HCV. DTT patients were more likely to be initiated on HCV treatment compared to standard of care (SOC), lending support for similar programs of remote engagement in HCV care.

BackgroundAlthough unhealthy alcohol use is associated with increased morbidity and mortality among people with HIV (PWH), many are ambivalent about engaging in treatment and experience variable responses to treatment. We describe the rationale, aims, and study design for the Financial Incentives, Randomization, with Stepped Treatment (FIRST) Trial, a multi-site randomized controlled efficacy trial.MethodsPWH in care recruited from clinics across the United States who reported unhealthy alcohol use, had a phosphatidylethanol (PEth) >20 ng/mL, and were not engaged in formal alcohol treatment were randomized to integrated contingency management with stepped care versus treatment as usual. The intervention involved two steps; Step 1: Contingency management (n = 5 sessions) with potential rewards based on 1) short-term abstinence; 2) longer-term abstinence; and 3) completion of healthy activities to promote progress in addressing alcohol consumption or conditions potentially impacted by alcohol; Step 2: Addiction physician management (n = 6 sessions) plus motivational enhancement therapy (n = 4 sessions). Participants' treatment was stepped up at week 12 if they lacked evidence of longer-term abstinence. Primary outcome was abstinence at week 24. Secondary outcomes included alcohol consumption (assessed by TLFB and PEth) and the Veterans Aging Cohort Study (VACS) Index 2.0 scores; exploratory outcomes included progress in addressing medical conditions potentially impacted by alcohol. Protocol adaptations due to the COVID-19 pandemic are described.ConclusionsThe FIRST Trial is anticipated to yield insights on the feasibility and preliminary efficacy of integrated contingency management with stepped care to address unhealthy alcohol use among PWH.Clinicaltrialsgov identifier: NCT03089320.

ObjectiveAs part of a project to implement antimicrobial dashboards at select facilities, we assessed physician attitudes and knowledge regarding antibiotic prescribing.DesignAn online survey explored attitudes toward antimicrobial use and assessed respondents' management of four clinical scenarios: cellulitis, community-acquired pneumonia, non-catheter-associated asymptomatic bacteriuria, and catheter-associated asymptomatic bacteriuria.SettingThis study was conducted across 16 Veterans' Affairs (VA) medical centers in 2017.ParticipantsPhysicians working in inpatient settings specializing in infectious diseases (ID), hospital medicine, and non-ID/hospitalist internal medicine.MethodsScenario responses were scored by assigning +1 for answers most consistent with guidelines, 0 for less guideline-concordant but acceptable answers and -1 for guideline-discordant answers. Scores were normalized to 100% guideline concordant to 100% guideline discordant across all questions within a scenario, and mean scores were calculated across respondents by specialty. Differences in mean score per scenario were tested using analysis of variance (ANOVA).ResultsOverall, 139 physicians completed the survey (19 ID physicians, 62 hospitalists, and 58 other internists). Attitudes were similar across the 3 groups. We detected a significant difference in cellulitis scenario scores (concordance: ID physicians, 76%; hospitalists, 58%; other internists, 52%; P = .0087). Scores were numerically but not significantly different across groups for community-acquired pneumonia (concordance: ID physicians, 75%; hospitalists, 60%; other internists, 56%; P = .0914), for non-catheter-associated asymptomatic bacteriuria (concordance: ID physicians, 65%; hospitalists, 55%; other internists, 40%; P = .322), and for catheter-associated asymptomatic bacteriuria (concordance: ID physicians, 27% concordant; hospitalists, 8% discordant; other internists 13% discordant; P = .12).ConclusionsSignificant differences in performance regarding management of cellulitis and low overall performance regarding asymptomatic bacteriuria point to these conditions as being potentially high-yield targets for stewardship interventions.

We explored experiences and perceptions surrounding the Self-Stewardship Time-Out Program (SSTOP) intervention across implementation sites to improve antimicrobial use. Semistructured qualitative interviews were conducted with Antibiotic Stewardship physicians and pharmacists, from which 5 key themes emerged. SSTOP may serve to achieve sustainable promotion of antibiotic use improvements.

BackgroundImproving the identification of people who inject drugs (PWID) in electronic medical records can improve clinical decision making, risk assessment and mitigation, and health service research. Identification of PWID currently consists of heterogeneous, nonspecific International Classification of Diseases (ICD) codes as proxies. Natural language processing (NLP) and machine learning (ML) methods may have better diagnostic metrics than nonspecific ICD codes for identifying PWID.MethodsWe manually reviewed 1000 records of patients diagnosed with Staphylococcus aureus bacteremia admitted to Veterans Health Administration hospitals from 2003 through 2014. The manual review was the reference standard. We developed and trained NLP/ML algorithms with and without regular expression filters for negation (NegEx) and compared these with 11 proxy combinations of ICD codes to identify PWID. Data were split 70% for training and 30% for testing. We calculated diagnostic metrics and estimated 95% confidence intervals (CIs) by bootstrapping the hold-out test set. Best models were determined by best F-score, a summary of sensitivity and positive predictive value.ResultsRandom forest with and without NegEx were the best-performing NLP/ML algorithms in the training set. Random forest with NegEx outperformed all ICD-based algorithms. F-score for the best NLP/ML algorithm was 0.905 (95% CI, .786-.967) and 0.592 (95% CI, .550-.632) for the best ICD-based algorithm. The NLP/ML algorithm had a sensitivity of 92.6% and specificity of 95.4%.ConclusionsNLP/ML outperformed ICD-based coding algorithms at identifying PWID in electronic health records. NLP/ML models should be considered in identifying cohorts of PWID to improve clinical decision making, health services research, and administrative surveillance.

BackgroundHospitals are required to have antibiotic stewardship programs (ASPs), but there are few models for implementing ASPs without the support of an infectious disease (ID) specialist, defined as an ID physician and/or ID pharmacist.ObjectiveIn this study, we sought to understand ASP implementation at hospitals that lack on-site ID support within the Veterans' Health Administration (VHA).MethodsUsing a mandatory VHA survey, we identified acute-care hospitals that lacked an on-site ID specialist. We conducted semistructured interviews with personnel involved in ASP activities.SettingThe study was conducted across 7 VHA hospitals.ParticipantsIn total, 42 hospital personnel were enrolled in the study.ResultsThe primary responsibility for ASPs fell on the pharmacist champions, who were typically assigned multiple other non-ASP responsibilities. The pharmacist champions were more successful at gaining buy-in when they had established rapport with clinicians, but at some sites, the use of contract physicians and frequent staff turnover were potential barriers. Some sites felt that having access to an off-site ID specialist was important for overcoming institutional barriers and improving the acceptance of their stewardship recommendations. In general, stewardship champions struggled to mobilize institutional resources, which made it difficult to advance their programmatic goals.ConclusionIn this study of 7 hospitals without on-site ID support, we found that ASPs are largely a pharmacy-driven process. Remote ID support, if available, was seen as helpful for implementing stewardship interventions. These findings may inform the future implementation of ASPs in settings lacking local ID expertise.

BackgroundAlthough many large, randomized controlled trials (RCT) have been conducted on antibiotic therapy for patients with primary C. difficile infections (CDI), few RCTs have been performed for patients with recurrent CDI (rCDI). In addition, fecal microbial transplant (FMT) is neither FDA-approved or guideline-recommended for patients with pauci-rCDI (first or second recurrences). Therefore, a rigorous RCT of sufficient size was designed to determine the optimal treatment among three antibiotic regimens in current practice for treatment of pauci-rCDI.MethodsVA Cooperative Studies Program (CSP) #596 is a prospective, double-blind, multi-center clinical trial of veteran patients with pauci-rCDI comparing fidaxomicin (FDX) 200 mg twice daily for 10 days and vancomycin (VAN) 125 mg four times daily for 10 days followed by a 3-week vancomycin taper and pulse (VAN-T/P) regimen to a standard course of VAN 125 mg four times daily for 10 days. The primary endpoint is sustained clinical response at day 59, with sustained response measured as a diarrhea composite outcome (D-COM) that includes symptom resolution during treatment (before day 10) without recurrence of diarrhea or other clinically important outcomes through day 59.DiscussionCSP study 596 is designed to compare three current antibiotic treatments for recurrent CDI that are in clinical practice, but which lack high-quality evidence to support strong guideline recommendations. The design of the study which included a pilot phase initiated at six sites with expansion to 24 sites is described along with protocol modifications based on early trial experience and clinical realities including the COVID-19 pandemic.Trial registrationThis study is registered with clinicaltrials.gov (Identifier: NCT02667418).

ObjectiveTobacco use/smoking for epidemiologic studies is often derived from electronic health record (EHR) data, which may be inaccurate. We previously compared smoking from the United States Veterans Health Administration (VHA) EHR clinical reminder data with survey data and found excellent agreement. However, the smoking clinical reminder items changed October 1, 2018. We sought to use the biomarker salivary cotinine (cotinine ≥30) to validate current smoking from multiple sources.Materials and methodsWe included 323 Veterans Aging Cohort Study participants with cotinine, clinical reminder, and self-administered survey smoking data from October 1, 2018 to September 30, 2019. We included International Classification of Disease (ICD)-10 codes F17.21 and Z72.0. Operating characteristics and kappa statistics were calculated.ResultsParticipants were mostly male (96%), African American (75%) and mean age was 63 years. Of those identified as currently smoking based on cotinine, 86%, 85%, and 51% were identified as currently smoking based on clinical reminder, survey, and ICD-10 codes, respectively. Of those identified as not currently smoking based on cotinine, 95%, 97%, and 97% were identified as not currently smoking based on clinical reminder, survey, and ICD-10 codes. Agreement with cotinine was substantial for clinical reminder (kappa = .81) and survey (kappa = .83), but only moderate for ICD-10 (kappa = .50).DiscussionTo determine current smoking, clinical reminder, and survey agreed well with cotinine, whereas ICD-10 codes did not. Clinical reminders could be used in other health systems to capture more accurate smoking information.ConclusionsClinical reminders are an excellent source for self-reported smoking status and are readily available in the VHA EHR.

ObjectiveTo assess the effectiveness and acceptability of antimicrobial stewardship-focused implementation strategies on inpatient fluoroquinolones.MethodsStewardship champions at 15 hospitals were surveyed regarding the use and acceptability of strategies to improve fluoroquinolone prescribing. Antibiotic days of therapy (DOT) per 1,000 days present (DP) for sites with and without prospective audit and feedback (PAF) and/or prior approval were compared.ResultsAmong all of the sites, 60% had PAF or prior approval implemented for fluoroquinolones. Compared to sites using neither strategy (64.2 ± 34.4 DOT/DP), fluoroquinolone prescribing rates were lower for sites that employed PAF and/or prior approval (35.5 ± 9.8; P = .03) and decreased from 2017 to 2018 (P < .001). This decrease occurred without an increase in advanced-generation cephalosporins. Total antibiotic rates were 13% lower for sites with PAF and/or prior approval, but this difference did not reach statistical significance (P = .20). Sites reporting that PAF and/or prior approval were "completely" accepted had lower fluoroquinolone rates than sites where it was "moderately" accepted (34.2 ± 5.7 vs 48.7 ± 4.5; P < .01). Sites reported that clinical pathways and/or local guidelines (93%), prior approval (93%), and order forms (80%) "would" or "may" be effective in improving fluoroquinolone use. Although most sites (73%) indicated that requiring infectious disease consults would or may be effective in improving fluoroquinolones, 87% perceived implementation to be difficult.ConclusionsPAF and prior approval implementation strategies focused on fluoroquinolones were associated with significantly lower fluoroquinolone prescribing rates and nonsignificant decreases in total antibiotic use, suggesting limited evidence for class substitution. The association of acceptability of strategies with lower rates highlights the importance of culture. These results may indicate increased acceptability of implementation strategies and/or sensitivity to FDA warnings.

BackgroundThe Core Elements of Outpatient Antibiotic Stewardship provide a framework to improve antibiotic use. We report the impact of core elements implementation within Veterans Health Administration sites.MethodsIn this quasiexperimental controlled study, effects of an intervention targeting antibiotic prescription for uncomplicated acute respiratory tract infections (ARIs) were assessed. Outcomes included per-visit antibiotic prescribing, treatment appropriateness, ARI revisits, hospitalization, and ARI diagnostic changes over a 3-year pre-implementation period and 1-year post-implementation period. Logistic regression adjusted for covariates (odds ratio [OR], 95% confidence interval [CI]) and a difference-in-differences analysis compared outcomes between intervention and control sites.ResultsFrom 2014-2019, there were 16 712 and 51 275 patient visits within 10 intervention and 40 control sites, respectively. Antibiotic prescribing rates pre- and post-implementation within intervention sites were 59.7% and 41.5%, compared to 73.5% and 67.2% within control sites, respectively (difference-in-differences, P < .001). Intervention site pre- and post-implementation OR to receive appropriate therapy increased (OR, 1.67; 95% CI, 1.31-2.14), which remained unchanged within control sites (OR,1.04; 95% CI, .91-1.19). ARI-related return visits post-implementation (-1.3% vs -2.0%; difference-in-differences P = .76) were not different, but all-cause hospitalization was lower within intervention sites (-0.5% vs -0.2%; difference-in-differences P = .02). The OR to diagnose non-specific ARI compared with non-ARI diagnoses increased post-implementation forintervention (OR, 1.27; 95% CI, 1.21 -1.34) but not control (OR, 0.97; 95% CI, .94-1.01) sites.ConclusionsImplementation of the core elements was associated with reduced antibiotic prescribing for RIs and a reduction in hospitalizations. Diagnostic coding changes were observed.

We characterized serology following a nursing home outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) where residents were serially tested by reverse-transcription polymerase chain reaction (RT-PCR) and positive residents were cohorted. When tested 46-76 days later, 24 of 26 RT-PCR-positive residents were seropositive; none of the 124 RT-PCR-negative residents had confirmed seropositivity, supporting serial SARS-CoV-2 RT-PCR testing and cohorting in nursing homes.

IntroductionThe optimal method for implementing hospital-level restrictions for antibiotics that carry a high risk of Clostridioides difficile infection has not been identified. We aimed to explore barriers and facilitators to implementing restrictions for fluoroquinolones and third/fourth-generation cephalosporins.MethodsThis mixed-methods study across a purposeful sample of 15 acute-care, geographically dispersed Veterans Health Administration hospitals included electronic surveys and semi-structured interviews (September 2018 to May 2019). Surveys on stewardship strategies were administered at each hospital and summarized with descriptive statistics. Interviews were performed with 30 antibiotic stewardship programme (ASP) champions across all 15 sites and 19 additional stakeholders at a subset of 5 sites; transcripts were analysed using thematic content analysis.ResultsThe most restricted agent was moxifloxacin, which was restricted at 12 (80%) sites. None of the 15 hospitals restricted ceftriaxone. Interviews identified differing opinions on the feasibility of restricting third/fourth-generation cephalosporins and fluoroquinolones. Some participants felt that restrictions could be implemented in a way that was not burdensome to clinicians and did not interfere with timely antibiotic administration. Others expressed concerns about restricting these agents, particularly through prior approval, given their frequent use, the difficulty of enforcing restrictions and potential unintended consequences of steering clinicians towards non-restricted antibiotics. A variety of stewardship strategies were perceived to be effective at reducing the use of these agents.ConclusionsAcross 15 hospitals, there were differing opinions on the feasibility of implementing antibiotic restrictions for third/fourth-generation cephalosporins and fluoroquinolones. While the perceived barrier to implementing restrictions was frequently high, many hospitals were effectively using restrictions and reported few barriers to their use.

ObjectiveTo evaluate antimicrobial stewards' experiences of using a dashboard display integrating local and national antibiotic use data implemented in the U.S. Department of Veterans Affairs (VA). This paper reports early formative evaluation.DesignQualitative interviewing.SettingEight VA hospitals participated with established antimicrobial stewardship (AS) programs participated in the pilot.ParticipantsSix infectious disease physicians and eight clinical pharmacists agreed to be interviewed (n = 14).MethodsA 3-part qualitative interview script was used involving a description of local stewardship activities, a Critical Incident description of dashboard use, and general questions regarding attitudes towards the tool. An inductive open coding approach was used for analysis.ResultsWe found 4 themes showing the complexities of using stewardship tools: (1) Data validity is socially negotiated; (2) Performance feedback motivates and persuades social goals when situated in an empirical distribution; (3) Shared problem awareness is aided by authoritative data; and (4) The AS dashboard encourages connections with local quality improvement culture.ConclusionsSocial dimensions of AS tool use emerged as distinct from, and equally important as decision support provided by the dashboard. Successful stewardship tools should be designed to support both the social and cognitive needs of users.

ObjectiveTo 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.DesignPropensity score-matched cohort of statin-exposed and unexposed patients from 2002 to 2017 in the Veterans Aging Cohort Study (VACS), a large cohort with cancer registry linkage and detailed pharmacy data.MethodsWe 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), nonmicrobial cancers, and mortality.Results:The propensity score-matched sample (N = 47 940) included 23 970 statin initiators (31% PWH). Incident cancers were diagnosed in 1160 PWH and 2116 uninfected patients. Death was reported in 1667 (7.0%) statin-exposed, and 2215 (9.2%) unexposed patients. Statin use was associated with 24% decreased risk of microbial-associated cancers (hazard ratio 0.76; 95% CI 0.69-0.85), but was not associated with nonmicrobial cancer risk (hazard ratio 1.00; 95% CI 0.92-1.09). Statin use was associated with 33% lower risk of death overall (hazard ratio 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 (hazard ratio 0.56; 95% CI 0.38-0.83) for PWH, but not for uninfected (P interaction = 0.012).ConclusionIn both PWH and uninfected, statin exposure was associated with lower risk of microbial, but not nonmicrobial cancer incidence, and with decreased mortality.

BackgroundThe 2019 American Thoracic Society/Infectious Diseases Society of America guidelines for community-acquired pneumonia (CAP) revised recommendations for culturing and empiric broad-spectrum antibiotics. We simulated guideline adoption in Veterans Affairs (VA) inpatients.MethodsFor all VA acute hospitalizations for CAP from 2006-2016 nationwide, we compared observed with guideline-expected proportions of hospitalizations with initial blood and respiratory cultures obtained, empiric antibiotic therapy with activity against methicillin-resistant Staphylococcus aureus (anti-MRSA) or Pseudomonas aeruginosa (antipseudomonal), empiric "overcoverage" (receipt of anti-MRSA/antipseudomonal therapy without eventual detection of MRSA/P. aeruginosa on culture), and empiric "undercoverage" (lack of anti-MRSA/antipseudomonal therapy with eventual detection on culture).ResultsOf 115 036 CAP hospitalizations over 11 years, 17 877 (16%) were admitted to an intensive care unit (ICU). Guideline adoption would slightly increase respiratory culture (30% to 36%) and decrease blood culture proportions (93% to 36%) in hospital wards and increase both respiratory (40% to 100%) and blood (95% to 100%) cultures in ICUs. Adoption would decrease empiric selection of anti-MRSA (ward: 27% to 1%; ICU: 61% to 8%) and antipseudomonal (ward: 25% to 1%; ICU: 54% to 9%) therapies. This would correspond to greatly decreased MRSA overcoverage (ward: 27% to 1%; ICU: 56% to 8%), slightly increased MRSA undercoverage (ward: 0.6% to 1.3%; ICU: 0.5% to 3.3%), with similar findings for P. aeruginosa. For all comparisons, P

ObjectiveTo examine how individual steward characteristics (eg, steward role, sex, and specialized training) are associated with their views of antimicrobial stewardship program (ASP) implementation at their institution.DesignDescriptive survey from a mixed-methods study.SettingTwo large national healthcare systems; the Veterans' Health Administration (VA) (n = 134 hospitals) and Intermountain Healthcare (IHC; n = 20 hospitals).ParticipantsWe sent the survey to 329 antibiotic stewards serving in 154 hospitals; 152 were physicians and 177 were pharmacists. In total, 118 pharmacists and 64 physicians from 126 hospitals responded.MethodsThe survey was grounded in constructs of the Consolidated Framework for Implementation Research, and it assessed stewards' views on the development and implementation of antibiotic stewardship programs (ASPs) at their institutions We then examined differences in stewards' views by demographic factors.ResultsRegardless of individual factors, stewards agreed that the ASP added value to their institution and was advantageous to patient care. Stewards also reported high levels of collegiality and self-efficacy. Stewards who had specialized training or those volunteered for the role were less likely to think that the ASP was implemented due to a mandate. Similarly volunteers and those with specialized training felt that they had authority in the antibiotic decisions made in their facility.ConclusionsGiven the importance of ASPs, it may be beneficial for healthcare institutions to recruit and train individuals with a true interest in stewardship.

The objective of this study was to evaluate the association between fluoroquinolone (FQ) use and the occurrence of aortic aneurysm/dissection (AA/AD), acute myocardial infarction (AMI), ventricular arrhythmias (VenA), and all-cause mortality vs other commonly used antibiotics. We conducted a self-controlled case series analysis of patients who experienced the outcomes of AA/AD, AMI, and VenA, based on diagnosis codes from emergency department visits and hospitalizations within Veterans Health Administration, and death in FY2014-FY2018. These Veterans also received outpatient prescriptions for FQs. Conditional Poisson regression models were used to estimate the association between FQs and each of the outcomes vs antibiotics of interest (ie amoxicillin or amoxicillin/clavulanate, azithromycin, doxycycline, cefuroxime or cephalexin, or sulfamethoxazole-trimethoprim), adjusted for time-varying covariates. Using a 30-day risk period after each antibiotic prescription, adjusted incidence rate ratios (aIRRs) for FQs vs each comparator antibiotic were not statistically different for outcomes of VenA or AMI. For AA/AD, incidence was higher during FQ risk periods vs amoxicillin [aIRR 1.50 (95% CI 1.01, 2.25)] and azithromycin [aIRR 2.15 (95% CI 1.27, 3.64)] risk periods. A significantly increased risk of mortality was observed with FQs vs each antibiotic of interest. FQs were associated with an increased risk of AA/AD vs amoxicillin and azithromycin and an increased risk of all-cause mortality vs multiple antibiotics commonly used for outpatient infections. Although the differences in event rates are small, FQ use should be limited to serious infections without appropriate alternatives.

BackgroundCohort studies identifying the incidence, complications and co-morbidities associated with community acquired pneumonia (CAP) are largely based on administrative datasets and rely on International Classification of Diseases (ICD) codes; however, the reliability of ICD codes for hospital admissions for CAP in people with HIV (PWH) has not been systematically assessed.MethodsWe used data from the Veterans Aging Cohort Study survey sample (N = 6824; 3410 PWH and 3414 uninfected) to validate the use of electronic health records (EHR) data to identify CAP hospitalizations when compared to chart review and to compare the performance in PWH vs. uninfected patients. We used different EHR algorithms that included a broad set of CAP ICD-9 codes, a set restricted to bacterial and viral CAP codes, and algorithms that included pharmacy data and/or other ICD-9 diagnoses frequently associated with CAP. We also compared microbiologic workup and etiologic diagnosis by HIV status among those with CAP.ResultsFive hundred forty-nine patients were identified as having an ICD-9 code compatible with a CAP diagnosis (13% of PWH and 4% of the uninfected, p

We describe a widespread laboratory surveillance program for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) at an integrated medical campus that includes a tertiary-care center, a skilled nursing facility, a rehabilitation treatment center, and temporary shelter units. We identified 22 asymptomatic cases of SARS-CoV-2 and implemented infection control measures to prevent SARS-CoV-2 transmission in congregate settings.

BackgroundAntimicrobial stewards may benefit from comparative data to inform interventions that promote optimal inpatient antimicrobial use.MethodsAntimicrobial stewards from 8 geographically dispersed Veterans Affairs (VA) inpatient facilities participated in the development of antimicrobial use visualization tools that allowed for comparison to facilities of similar complexity. The visualization tools consisted of an interactive web-based antimicrobial dashboard and, later, a standardized antimicrobial usage report updated at user-selected intervals. Stewards participated in monthly learning collaboratives. The percent change in average monthly antimicrobial use (all antimicrobial agents, anti-methicillin-resistant Staphylococcus aureus [anti-MRSA] agents, and antipseudomonal agents) was analyzed using a pre-post (January 2014-January 2016 vs July 2016-January 2018) design with segmented regression and external comparison with uninvolved control facilities (n = 118).ResultsIntervention sites demonstrated a 2.1% decrease (95% confidence interval [CI], -5.7% to 1.6%) in total antimicrobial use pre-post intervention vs a 2.5% increase (95% CI, 0.8% to 4.1%) in nonintervention sites (absolute difference, 4.6%; P = .025). Anti-MRSA antimicrobial use decreased 11.3% (95% CI, -16.0% to -6.3%) at intervention sites vs a 6.6% decrease (95% CI, -9.1% to -3.9%) at nonintervention sites (absolute difference, 4.7%; P = .092). Antipseudomonal antimicrobial use decreased 3.4% (95% CI, -8.2% to 1.7%) at intervention sites vs a 3.6% increase (95% CI, 0.8% to 6.5%) at nonintervention sites (absolute difference, 7.0%; P = .018).ConclusionsComparative data visualization tool use by stewards at 8 VA facilities was associated with significant reductions in overall antimicrobial and antipseudomonal use relative to uninvolved facilities.

BackgroundPeople with human immunodeficiency virus (PWH) face increased risks for heart failure and adverse heart failure outcomes. Myocardial steatosis predisposes to diastolic dysfunction, a heart failure precursor. We aimed to characterize myocardial steatosis and associated potential risk factors among a subset of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) participants.MethodsEighty-two PWH without known heart failure successfully underwent cardiovascular magnetic resonance spectroscopy, yielding data on intramyocardial triglyceride (IMTG) content (a continuous marker for myocardial steatosis extent). Logistic regression models were applied to investigate associations between select clinical characteristics and odds of increased or markedly increased IMTG content.ResultsMedian (Q1, Q3) IMTG content was 0.59% (0.28%, 1.15%). IMTG content was increased (> 0.5%) among 52% and markedly increased (> 1.5%) among 22% of participants. Parameters associated with increased IMTG content included age (P = .013), body mass index (BMI) ≥ 25 kg/m2 (P = .055), history of intravenous drug use (IVDU) (P = .033), and nadir CD4 count

BackgroundAntibiotic stewardship programs (ASPs) are required at every hospital regardless of size. We conducted a qualitative study across different hospital settings to examine perspectives of physician and pharmacist stewards about the dynamics within their team and contextual factors that facilitate the success of their programs.MethodsSemistructured interviews were conducted in March-November 2018 with 46 ASP stewards, 30 pharmacists, and 16 physicians, from 39 hospitals within 2 large hospital systems.ResultsWe identified 5 major themes: antibiotic stewards were enthusiastic about their role, committed to the goals of stewardship for their patients and as a public-health imperative, and energized by successful interventions; responsibilities of pharmacist and physician stewards are markedly different, and pharmacy stewards performed the majority of the day-to-day stewardship work; collaborative teamwork is important to improving care, the pharmacists and physicians supported each other, and pharmacists believed that having a strong physician leader was essential; provider engagement strategies are a critical component of stewardship, and recommendations must be communicated in a collegial manner that did not judge the provider competence, preferably through face-to-face interactions; and hospital leadership support for ASP goals and for protected time for ASP activities is critical for success.ConclusionsThe physician-pharmacist team is essential for ASPs; most have pharmacists leading and performing day-to-day activities with physician support. Collaborative, persuasive approaches for ASP interventions were the norm. Stewards were careful not to criticize or judge inappropriate antibiotic prescribing. Further research should examine whether this persuasive approach undercuts provider appreciation of stewardship as a public health mandate.

BackgroundDespite increasing incidence of hepatocellular carcinoma (HCC) among HIV-infected patients, it remains unclear if HIV-related factors contribute to development of HCC. We examined if higher or prolonged HIV viremia and lower CD4+ cell percentage were associated with HCC.MethodsWe conducted a cohort study of HIV-infected individuals who had HIV RNA, CD4+, and CD8+ cell counts and percentages assessed in the Veterans Aging Cohort Study (1999-2015). HCC was ascertained using Veterans Health Administration cancer registries and electronic records. Cox regression was used to determine hazard ratios (HR, 95% confidence interval [CI]) of HCC associated with higher current HIV RNA, longer duration of detectable HIV viremia (≥500 copies/mL), and current CD4+ cell percentage less than 14%, adjusting for traditional HCC risk factors. Analyses were stratified by previously validated diagnoses of cirrhosis prior to start of follow-up.ResultsAmong 35 659 HIV-infected patients, 302 (0.8%) developed HCC over 281 441 person-years (incidence rate = 107.3 per 100 000 person-years). Among patients without baseline cirrhosis, higher HIV RNA (HR = 1.25, 95% CI = 1.12 to 1.40, per 1.0 log10 copies/mL) and 12 or more months of detectable HIV (HR = 1.47, 95% CI = 1.02 to 2.11) were independently associated with higher risk of HCC. CD4+ percentage less than 14% was not associated with HCC in any model. Hepatitis C coinfection was a statistically significant predictor of HCC regardless of baseline cirrhosis status.ConclusionAmong HIV-infected patients without baseline cirrhosis, higher HIV RNA and longer duration of HIV viremia increased risk of HCC, independent of traditional HCC risk factors. This is the strongest evidence to date that HIV viremia contributes to risk of HCC in this group.

ImportanceUse of empirical broad-spectrum antibiotics for pneumonia has increased owing to concern for resistant organisms, including methicillin-resistant Staphylococcus aureus (MRSA). The association of empirical anti-MRSA therapy with outcomes among patients with pneumonia is unknown, even for high-risk patients.ObjectiveTo compare 30-day mortality among patients hospitalized for pneumonia receiving empirical anti-MRSA therapy vs standard empirical antibiotic regimens.Design, setting, and participantsRetrospective multicenter cohort study was conducted of all hospitalizations in which patients received either anti-MRSA or standard therapy for community-onset pneumonia in the Veterans Health Administration health care system from January 1, 2008, to December 31, 2013. Subgroups of patients analyzed were those with initial intensive care unit admission, MRSA risk factors, positive results of a MRSA surveillance test, and positive results of a MRSA admission culture. Primary analysis was an inverse probability of treatment-weighted propensity score analysis using generalized estimating equation regression; secondary analyses included an instrumental variable analysis. Statistical analysis was conducted from June 14 to November 20, 2019.ExposuresEmpirical anti-MRSA therapy plus standard pneumonia therapy vs standard therapy alone within the first day of hospitalization.Main outcomes and measuresRisk of 30-day all-cause mortality after adjustment for patient comorbidities, vital signs, and laboratory results. Secondary outcomes included the development of kidney injury and secondary infections with Clostridioides difficile, vancomycin-resistant Enterococcus species, or gram-negative bacilli.ResultsAmong 88 605 hospitalized patients (86 851 men; median age, 70 years [interquartile range, 62-81 years]), empirical anti-MRSA therapy was administered to 33 632 (38%); 8929 patients (10%) died within 30 days. Compared with standard therapy alone, in weighted propensity score analysis, empirical anti-MRSA therapy plus standard therapy was significantly associated with an increased adjusted risk of death (adjusted risk ratio [aRR], 1.4 [95% CI, 1.3-1.5]), kidney injury (aRR, 1.4 [95% CI, 1.3-1.5]), and secondary C difficile infections (aRR, 1.6 [95% CI, 1.3-1.9]), vancomycin-resistant Enterococcus spp infections (aRR, 1.6 [95% CI, 1.0-2.3]), and secondary gram-negative rod infections (aRR, 1.5 [95% CI, 1.2-1.8]). Similar associations between anti-MRSA therapy use and 30-day mortality were found by instrumental variable analysis (aRR, 1.6 [95% CI, 1.4-1.9]) and among patients admitted to the intensive care unit (aRR, 1.3 [95% CI, 1.2-1.5]), those with a high risk for MRSA (aRR, 1.2 [95% CI, 1.1-1.4]), and those with MRSA detected on surveillance testing (aRR, 1.6 [95% CI, 1.3-1.9]). No significant favorable association was found between empirical anti-MRSA therapy and death among patients with MRSA detected on culture (aRR, 1.1 [95% CI, 0.8-1.4]).Conclusions and relevanceThis study suggests that empirical anti-MRSA therapy was not associated with reduced mortality for any group of patients hospitalized for pneumonia. These results contribute to a growing body of evidence that questions the value of empirical use of anti-MRSA therapy using existing risk approaches.

BackgroundLiver fibrosis, is independently associated with incident heart failure (HF). Investigating the association between liver fibrosis and type of HF, specifically HF with reduced ejection fraction (EF; HFrEF) or HF with preserved ejection fraction (HFpEF), may provide mechanistic insight into this association. We sought to determine the association between liver fibrosis score (FIB-4) and type of HF, and to assess whether HIV or hepatitis C status modified this association.MethodsWe included patients alive on or after 4/1/2003 from the Veterans Aging Cohort Study. We followed patients without prevalent cardiovascular disease until their first HF event, death, last clinic visit, or 9/30/2015. We defined liver fibrosis as: likely advanced fibrosis (FIB-4 > 3.25), indeterminate (FIB-4 range 1.45-3.25), unlikely advanced fibrosis (FIB-4

BackgroundNorovirus is an important cause of epidemic acute gastroenteritis (AGE), yet the burden of endemic disease in adults has not been well documented. We estimated the prevalence and incidence of outpatient and community-acquired inpatient norovirus AGE at 4 Veterans Affairs Medical Centers (VAMC) (Atlanta, Georgia; Bronx, New York; Houston, Texas; and Los Angeles, California) and examined trends over 4 surveillance years.MethodsFrom November 2011 to September 2015, stool specimens collected within 7 days of AGE symptom onset for clinician-requested diagnostic testing were tested for norovirus, and positive samples were genotyped. Incidence was calculated by multiplying norovirus prevalence among tested specimens by AGE-coded outpatient encounters and inpatient discharges, and dividing by the number of unique patients served.ResultsOf 1603 stool specimens, 6% tested were positive for norovirus; GII.4 viruses (GII.4 New Orleans [17%] and GII.4 Sydney [47%]) were the most common genotypes. Overall prevalence and outpatient and inpatient community-acquired incidence followed a seasonal pattern, with higher median rates during November-April (9.2%, 376/100 000, and 45/100 000, respectively) compared to May-October (3.0%, 131/100 000, and 13/100 000, respectively). An alternate-year pattern was also detected, with highest peak prevalence and outpatient and inpatient community-acquired norovirus incidence rates in the first and third years of surveillance (14%-25%, 349-613/100 000, and 43-46/100 000, respectively).ConclusionsThis multiyear analysis of laboratory-confirmed AGE surveillance from 4 VAMCs demonstrates dynamic intra- and interannual variability in prevalence and incidence of outpatient and inpatient community-acquired norovirus in US Veterans, highlighting the burden of norovirus disease in this adult population.

Rationale: The 2016 guidelines for hospital-acquired pneumonia (HAP) suggest applying a universal antibiogram resistance threshold in addition to patient criteria to determine empiric coverage. The impact of these recommendations is unknown.Objectives: 1) Describe national antibiotic use and microbiology patterns for HAP among patients with noninfectious admissions, 2) measure the predictive performance of the antibiogram threshold and risk factors, and 3) estimate the change in practice with guideline implementation.Methods: We conducted a retrospective analysis of all hospitalizations without initial infection but with secondary pneumonia diagnoses at Veterans Affairs Medical Centers between October 1, 2012, and September 30, 2015. For each hospitalization we extracted: presence of methicillin-resistant Staphylococcus aureus (MRSA) and resistant gram-negative rods (R-GNR) in cultures, anti-MRSA and antipseudomonal antimicrobial administration, and facility-level prevalence of MRSA and R-GNR. We calculated the percentage of hospitalizations with resistant organisms, broad-spectrum antibiotics, and the predictive performance of patient characteristics and prevalence thresholds for MRSA.Results: Among 3,562 cases, 5.17% were positive for MRSA and 2.30% for R-GNR. The recommended MRSA prevalence threshold was 100.00% sensitive (95% confidence interval [CI], 98.02-100.00%) and 0.03% specific (95% CI, 0.00-0.16%) for MRSA-positive culture, leading to overtreatment of 94.81% (95% CI, 94.02-95.50%) of patients. Pressor order (odds ratio [OR], 3.89; 95% CI, 1.17-12.91) and intravenous antibiotics within the past 90 days (OR, 1.98; 95% CI, 1.03-3.81) were associated with MRSA. Mechanical ventilation was associated with R-GNR (OR, 4.37; 95% CI, 1.52-12.57).Conclusions: The guideline-recommended antibiogram threshold and characteristics did not improve prediction of MRSA or R-GNR and would have led to an increase in MRSA treatment.

BackgroundAntibiotics are overprescribed for acute respiratory tract infections (ARIs). Guidelines provide criteria to determine which patients should receive antibiotics. We assessed congruence between documentation of ARI diagnostic and treatment practices with guideline recommendations, treatment appropriateness, and outcomes.MethodsA multicenter quality improvement evaluation was conducted in 28 Veterans Affairs facilities. We included visits for pharyngitis, rhinosinusitis, bronchitis, and upper respiratory tract infections (URI-NOS) that occurred during the 2015-2016 winter season. A manual record review identified complicated cases, which were excluded. Data were extracted for visits meeting criteria, followed by analysis of practice patterns, guideline congruence, and outcomes.ResultsOf 5,740 visits, 4,305 met our inclusion criteria: pharyngitis (n = 558), rhinosinusitis (n = 715), bronchitis (n = 1,155), URI-NOS (n = 1,475), or mixed diagnoses (>1 ARI diagnosis) (n = 402). Antibiotics were prescribed in 68% of visits: pharyngitis (69%), rhinosinusitis (89%), bronchitis (86%), URI-NOS (37%), and mixed diagnosis (86%). Streptococcal diagnostic testing was performed in 33% of pharyngitis visits; group A Streptococcus was identified in 3% of visits. Streptococcal tests were ordered less frequently for patients who received antibiotics (28%) than those who did not receive antibiotics 44%; P < .01). Although 68% of visits for rhinosinusitis had documentation of symptoms, only 32% met diagnostic criteria for antibiotics. Overall, 39% of patients with uncomplicated ARIs received appropriate antibiotic management. The proportion of 30-day return visits for ARI care was similar for appropriate (11%) or inappropriate (10%) antibiotic management (P = .22).ConclusionsAntibiotics were prescribed in most uncomplicated ARI visits, indicating substantial overuse. Practice was frequently discordant with guideline diagnostic and treatment recommendations.

PurposePharmacoepidemiologic studies using electronic health record data could serve an important role in assessing safety and effectiveness of direct-acting antiviral therapy for chronic hepatitis C virus (HCV) infection, but the validity of these data needs to be determined. We evaluated the accuracy of pharmacy fill records in the national Veterans Health Administration (VA) Corporate Data Warehouse (CDW) as compared to facility-level electronic health record.MethodsPatients prescribed a direct-acting antiviral regimen at five VA sites between 2014 and 2016 were randomly selected and reviewed. A random sample of patients with chronic HCV infection without evidence of HCV treatment during the study period also underwent chart review. We calculated positive predictive value and negative predictive value overall and by site.ResultsOf the 501 patients who received a total of 2416 prescriptions, 494 were validated using data extracted from CDW 6 months after the study period, yielding a positive predictive value of 98.6% (95% confidence interval, 97.6%-99.6%). Of the 100 patients with chronic HCV infection without prescriptions for HCV treatment, 99 were confirmed not to have received antiviral treatment (negative predictive value, 99.0%; 95% confidence interval, 97.1%-100%).ConclusionsThese findings provide assurance to researchers who use national VA CDW data for retrospective cohort studies that the CDW contains accurate information on HCV therapies in the modern treatment era.

Objectives:Inappropriate antibiotic use poses a serious threat to patient safety. Antimicrobial stewardship programmes (ASPs) may optimize antimicrobial use and improve patient outcomes, but their implementation remains an organizational challenge. Using the Promoting Action on Research Implementation in Health Services (PARiHS) framework, this study aimed to identify organizational factors that may facilitate ASP design, development and implementation. Methods:Among 130 Veterans Affairs facilities that offered acute care, we classified organizational variables supporting antimicrobial stewardship activities into three PARiHS domains: evidence to encompass sources of knowledge; contexts to translate evidence into practice; and facilitation to enhance the implementation process. We conducted a series of exploratory factor analyses to identify conceptually linked factor scales. Cronbach's alphas were calculated. Variables with large uniqueness values were left as single factors. Results:We identified 32 factors, including six constructs derived from factor analyses under the three PARiHS domains. In the evidence domain, four factors described guidelines and clinical pathways. The context domain was broken into three main categories: (i) receptive context (15 factors describing resources, affiliations/networks, formalized policies/practices, decision-making, receptiveness to change); (ii) team functioning (1 factor); and (iii) evaluation/feedback (5 factors). Within facilitation, two factors described facilitator roles and tasks and five captured skills and training. Conclusions:We mapped survey data onto PARiHS domains to identify factors that may be adapted to facilitate ASP uptake. Our model encompasses mostly mutable factors whose relationships with performance outcomes may be explored to optimize antimicrobial use. Our framework also provides an analytical model for determining whether leveraging existing organizational processes can potentially optimize ASP performance.

ObjectiveTo test the effectiveness of a collaborative depression care model in improving depression and hepatitis C virus (HCV) care.Data sources/study settingHepatitis C virus clinic patients who screened positive for depression at four Veterans Affairs Hospitals.Study designWe compared off-site depression collaborative care (delivered by depression care manager, pharmacist, and psychiatrist) with usual care in a randomized trial. Primary depression outcomes were treatment response (≥50 percent decrease in 20-item Hopkins Symptoms Checklist [SCL-20] score), remission (mean SCL-20 score,

BACKGROUND:The effect of human immunodeficiency virus (HIV) on the development of peripheral artery disease (PAD) remains unclear. We investigated whether HIV infection is associated with an increased risk of PAD after adjustment for traditional atherosclerotic risk factors in a large cohort of HIV-infected (HIV+) and demographically similar HIV-uninfected veterans. METHODS:We studied participants in the Veterans Aging Cohort Study from April 1, 2003 through December 31, 2014. We excluded participants with known prior PAD or prevalent cardiovascular disease (myocardial infarction, stroke, coronary heart disease, and congestive heart failure) and analyzed the effect of HIV status on the risk of incident PAD events after adjusting for demographics, PAD risk factors, substance use, CD4 cell count, HIV-1 ribonucleic acid, and antiretroviral therapy. The primary outcome is incident peripheral artery disease events. Secondary outcomes include mortality and amputation in subjects with incident PAD events by HIV infection status, viral load, and CD4 count. RESULTS:Among 91 953 participants, over a median follow up of 9.0 years, there were 7708 incident PAD events. Rates of incident PAD events per 1000 person-years were higher among HIV+ (11.9; 95% confidence interval [CI], 11.5-12.4) than uninfected veterans (9.9; 95% CI, 9.6-10.1). After adjustment for demographics, PAD risk factors, and other covariates, HIV+ veterans had an increased risk of incident PAD events compared with uninfected veterans (hazard ratio [HR], 1.19; 95% CI, 1.13-1.25). This risk was highest among those with time-updated HIV viral load >500 copies/mL (HR, 1.51; 95% CI, 1.38-1.65) and CD4 cell counts

BackgroundViral suppression is a primary marker of HIV treatment success. Persons with HIV are at increased risk for AIDS-defining cancer (ADC) and several types of non-AIDS-defining cancer (NADC), some of which are caused by oncogenic viruses.ObjectiveTo determine whether viral suppression is associated with decreased cancer risk.DesignProspective cohort.SettingDepartment of Veterans Affairs.ParticipantsHIV-positive veterans (n = 42 441) and demographically matched uninfected veterans (n = 104 712) from 1999 to 2015.MeasurementsStandardized cancer incidence rates and Poisson regression rate ratios (RRs; HIV-positive vs. uninfected persons) by viral suppression status (unsuppressed: person-time with HIV RNA levels ≥500 copies/mL; early suppression: initial 2 years with HIV RNA levels

Bilirubin may protect against cardiovascular disease (CVD) by reducing oxidative stress. Whether elevated bilirubin reduces the risk of CVD events among HIV+ individuals and if this differs from uninfected individuals remain unclear. We assessed whether bilirubin independently predicted the risk of CVD events among HIV+ and uninfected participants in VACS (Veterans Aging Cohort Study). We conducted a prospective cohort study using VACS participants free of baseline CVD. Total bilirubin was categorized by quartiles. CVD as well as acute myocardial infarction, heart failure, and ischemic stroke events were assessed. Cox regression was used to evaluate hazard ratios of outcomes associated with quartiles of total bilirubin in HIV+ and uninfected people after adjusting for multiple risk factors. There were 96 381 participants (30 427 HIV+); mean age was 48 years, 48% were black, and 97% were men. There were 6603 total incident CVD events over a mean of 5.7 years. In adjusted models, increasing quartiles of baseline total bilirubin were associated with decreased hazards of all outcomes (hazard ratio, 0.86; 95% confidence interval, 0.80-0.91). Among HIV+ participants, results persisted for heart failure, ischemic stroke, and total CVD, but nonsignificant associations were observed for acute myocardial infarction. VACS participants (regardless of HIV status) with elevated bilirubin levels had a lower risk of incident total CVD, acute myocardial infarction, heart failure, and ischemic stroke events after adjusting for known risk factors. Future studies should investigate how this apparently protective effect of elevated bilirubin could be harnessed to reduce CVD risk or improve risk estimation among HIV+ individuals.

OBJECTIVE:Aging people living with HIV (PLWH) face an increased burden of comorbidities, including chronic obstructive pulmonary disease (COPD). The impact of COPD on mortality in HIV remains unclear. We examined associations between markers of COPD and mortality among PLWH and uninfected study participants. DESIGN:Longitudinal analysis of the Examinations of HIV-Associated Lung Emphysema (EXHALE) cohort study. METHODS:EXHALE includes 196 PLWH and 165 uninfected smoking-matched study participants who underwent pulmonary function testing and computed tomography (CT) to define COPD and were followed. We determined associations between markers of COPD with mortality using multivariable Cox regression models, adjusted for smoking and the Veterans Aging Cohort Study (VACS) Index, a validated predictor of mortality in HIV. RESULTS:Median follow-up time was 6.9 years; the mortality rate was 2.7/100 person-years among PLWH and 1.7/100 person-years among uninfected study participants (P = 0.11). The VACS Index was associated with mortality in both PLWH and uninfected study participants. In multivariable models, pulmonary function and CT characteristics defining COPD were associated with mortality in PLWH: those with airflow obstruction (forced expiratory volume in 1 s/ forced vital capacity 10% burden) had 2.4 times the risk of death [hazard ratio 2.4 (95% confidence interval 1.1-5.5)] compared with those with ≤ 10% emphysema. In uninfected subjects, pulmonary variables were not significantly associated with mortality, which may reflect fewer deaths limiting power. CONCLUSION:Markers of COPD were associated with greater mortality in PWLH, independent of the VACS Index. COPD is likely an important contributor to mortality in contemporary PLWH.

BackgroundPatients with human immunodeficiency virus (HIV) and/or chronic hepatitis C virus (HCV) infection may be prescribed statins as treatment for metabolic/cardiovascular disease, but it remains unclear if the risk of acute liver injury (ALI) is increased for statin initiators compared to nonusers in groups classified by HIV/HCV status.MethodsWe conducted a cohort study to compare rates of ALI in statin initiators vs nonusers among 7686 HIV/HCV-coinfected, 8155 HCV-monoinfected, 17739 HIV-monoinfected, and 36604 uninfected persons in the Veterans Aging Cohort Study (2000-2012). We determined development of (1) liver aminotransferases >200 U/L, (2) severe ALI (coagulopathy with hyperbilirubinemia), and (3) death, all within 18 months. Cox regression was used to determine propensity score-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of outcomes in statin initiators compared to nonusers across the groups.ResultsAmong HIV/HCV-coinfected patients, statin initiators had lower risks of aminotransferase levels >200 U/L (HR, 0.66 [95% CI, .53-.83]), severe ALI (HR, 0.23 [95% CI, .12-.46]), and death (HR, 0.36 [95% CI, .28-.46]) compared with statin nonusers. In the setting of chronic HCV alone, statin initiators had reduced risks of aminotransferase elevations (HR, 0.57 [95% CI, .45-.72]), severe ALI (HR, 0.15 [95% CI, .06-.37]), and death (HR, 0.42 [95% CI, .32-.54]) than nonusers. Among HIV-monoinfected patients, statin initiators had lower risks of aminotransferase increases (HR, 0.52 [95% CI, .40-.66]), severe ALI (HR, 0.26 [95% CI, .13-.55]), and death (HR, 0.19 [95% CI, .16-.23]) compared with nonusers. Results were similar among uninfected persons.ConclusionsRegardless of HIV and/or chronic HCV status, statin initiators had a lower risk of ALI and death within 18 months compared with statin nonusers.

BackgroundDrivers of differences in Clostridium difficile incidence across acute and long-term care facilities are poorly understood. We sought to obtain a comprehensive picture of C. difficile incidence and risk factors in acute and long-term care.MethodsWe conducted a case-cohort study of persons spending at least 3 days in one of 131 acute care or 120 long-term care facilities managed by the United States Veterans Health Administration between 2006 and 2012. Patient (n = 8) and facility factors (n = 5) were included in analyses. The outcome was the incidence of facility-onset laboratory-identified C. difficile infection (CDI), defined as a person with a positive C. difficile test without a positive test in the prior 8 weeks.ResultsCDI incidence in acute care was 5 times that observed in long-term care (median, 15.6 vs 3.2 per 10000 person-days). History of antibiotic use was greater in acute care compared to long-term care (median, 739 vs 513 per 1000 person-days) and explained 72% of the variation in C. difficile rates. Importation of C. difficile cases (acute care: patients with recent long-term care attributable infection; long-term care: residents with recent acute care attributable infection) was 3 times higher in long-term care as compared to acute care (median, 52.3 vs 16.2 per 10000 person-days).ConclusionsFacility-level antibiotic use was the main factor driving differences in CDI incidence between acute and long-term care. Importation of acute care C. difficile cases was a greater concern for long-term care as compared to importation of long-term care cases for acute care.

PurposeAmong patients dually infected with human immunodeficiency virus (HIV) and chronic hepatitis C virus (HCV), use of antiretroviral therapy (ART) containing mitochondrial toxic nucleoside reverse transcriptase inhibitors (mtNRTIs) might induce chronic hepatic injury, which could accelerate HCV-associated liver fibrosis and increase the risk of hepatic decompensation and death.MethodsWe conducted a cohort study among 1747 HIV/HCV patients initiating NRTI-containing ART within the Veterans Aging Cohort Study (2002-2009) to determine if cumulative mtNRTI use increased the risk of hepatic decompensation and death among HIV-/HCV-coinfected patients. Separate marginal structural models were used to estimate hazard ratios (HRs) of each outcome associated with cumulative exposure to ART regimens that contain mtNRTIs versus regimens that contain other NRTIs.ResultsOver 7033 person-years, we observed 97 (5.6%) decompensation events (incidence rate, 13.8/1000 person-years) and 125 (7.2%) deaths (incidence rate, 17.8 events/1000 person-years). The risk of hepatic decompensation increased with cumulative mtNRTI use (1-11 mo: HR, 1.79 [95% confidence interval (CI), 0.74-4.31]; 12-35 mo: HR, 1.39 [95% CI, 0.68-2.87]; 36-71 mo: HR, 2.27 [95% CI, 0.92-5.60]; >71 mo: HR, 4.66 [95% CI, 1.04-20.83]; P = .045) versus nonuse. Cumulative mtNRTI use also increased risk of death (1-11 mo: HR, 2.24 [95% CI, 1.04-4.81]; 12-35 mo: HR, 2.05 [95% CI, 0.68-6.20]; 36-71 mo: HR, 3.04 [95% CI, 1.12-8.26]; >71 mo: HR, 3.93 [95% CI, 0.75-20.50]; P = .030).ConclusionsThese findings suggest that cumulative mtNRTI use may increase the risk of hepatic decompensation and death in HIV/HCV coinfection. These drugs should be avoided when alternatives exist for HIV/HCV patients.

OBJECTIVE To examine variation in antibiotic coverage and detection of resistant pathogens in community-onset pneumonia. DESIGN Cross-sectional study. SETTING A total of 128 hospitals in the Veterans Affairs health system. PARTICIPANTS Hospitalizations with a principal diagnosis of pneumonia from 2009 through 2010. METHODS We examined proportions of hospitalizations with empiric antibiotic coverage for methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PAER) and with initial detection in blood or respiratory cultures. We compared lowest- versus highest-decile hospitals, and we estimated adjusted probabilities (AP) for patient- and hospital-level factors predicting coverage and detection using hierarchical regression modeling. RESULTS Among 38,473 hospitalizations, empiric coverage varied widely across hospitals (MRSA lowest vs highest, 8.2% vs 42.0%; PAER lowest vs highest, 13.9% vs 44.4%). Detection rates also varied (MRSA lowest vs highest, 0.5% vs 3.6%; PAER lowest vs highest, 0.6% vs 3.7%). Whereas coverage was greatest among patients with recent hospitalizations (AP for anti-MRSA, 54%; AP for anti-PAER, 59%) and long-term care (AP for anti-MRSA, 60%; AP for anti-PAER, 66%), detection was greatest in patients with a previous history of a positive culture (AP for MRSA, 7.9%; AP for PAER, 11.9%) and in hospitals with a high prevalence of the organism in pneumonia (AP for MRSA, 3.9%; AP for PAER, 3.2%). Low hospital complexity and rural setting were strong negative predictors of coverage but not of detection. CONCLUSIONS Hospitals demonstrated widespread variation in both coverage and detection of MRSA and PAER, but probability of coverage correlated poorly with probability of detection. Factors associated with empiric coverage (eg, healthcare exposure) were different from those associated with detection (eg, microbiology history). Providing microbiology data during empiric antibiotic decision making could better align coverage to risk for resistant pathogens and could promote more judicious use of broad-spectrum antibiotics. Infect Control Hosp Epidemiol 2017;38:937-944.

ImportanceWith improved survival, heart failure (HF) has become a major complication for individuals with human immunodeficiency virus (HIV) infection. It is unclear if this risk extends to different types of HF in the antiretroviral therapy (ART) era. Determining whether HIV infection is associated with HF with reduced ejection fraction (HFrEF), HF with preserved ejection fraction (HFpEF), or both is critical because HF types differ with respect to underlying mechanism, treatment, and prognosis.ObjectivesTo investigate whether HIV infection increases the risk of future HFrEF and HFpEF and to assess if this risk varies by sociodemographic and HIV-specific factors.Design, setting, and participantsThis study evaluated 98 015 participants without baseline cardiovascular disease from the Veterans Aging Cohort Study, an observational cohort of HIV-infected veterans and uninfected veterans matched by age, sex, race/ethnicity, and clinical site, enrolled on or after April 1, 2003, and followed up through September 30, 2012. The dates of the analysis were October 2015 to November 2016.ExposureHuman immunodeficiency virus infection.Main outcomes and measuresOutcomes included HFpEF (EF≥50%), borderline HFpEF (EF 40%-49%), HFrEF (EF

BackgroundAntimicrobial stewardship programs (ASPs) have been advocated to improve antimicrobial utilization, but program implementation is variable. Antimicrobial stewardship programs (ASPs) have been advocated to improve antimicrobial utilization, but program implementation is variable.ObjectiveTo determine associations between ASPs and facility characteristics, and inpatient antimicrobial utilization measures in the Veterans Affairs (VA) system in 2012.DesignIn 2012, VA administered a survey on antimicrobial stewardship practices to designated ASP contacts at VA acute care hospitals. From the survey, we identified 34 variables across 3 domains (evidence, organizational context, and facilitation) that were assessed using multivariable least absolute shrinkage and selection operator regression against 4 antimicrobial utilization measures from 2012: aggregate acute care antimicrobial use, antimicrobial use in patients with non-infectious primary discharge diagnoses, missed opportunities to convert from parenteral to oral antimicrobial therapy, and double anaerobic coverage.SettingAll 130 VA facilities with acute care services.ResultsVariables associated with at least 3 favorable changes in antimicrobial utilization included presence of postgraduate physician/pharmacy training programs, number of antimicrobial-specific order sets, frequency of systematic de-escalation review, presence of pharmacists and/or infectious diseases (ID) attendings on acute care ward teams, and formal ID training of the lead ASP pharmacist. Variables associated with 2 unfavorable measures included bed size, the level of engagement with VA Antimicrobial Stewardship Task Force online resources, and utilization of antimicrobial stop orders.ConclusionsFormalization of ASP processes and presence of pharmacy and ID expertise are associated with favorable utilization. Systematic de-escalation review and order set establishment may be high-yield interventions. Journal of Hospital Medicine 2017;12:301-309.

BackgroundThe risk of hepatotoxicity with antiretroviral therapy (ART) remains unknown. We determined the comparative risk of acute liver injury (ALI) for antiretroviral drugs, classes, and regimens, by viral hepatitis status.MethodsWe followed a cohort of 10 083 human immunodeficiency virus (HIV)-infected persons in Kaiser Permanente Northern California (n = 2099) from 2004 to 2010 and the Veterans Aging Cohort Study (n = 7984) from 2004 to 2012. Within the first year of ART, we determined occurrence of (1) liver aminotransferases >200 U/L and (2) severe ALI (coagulopathy with hyperbilirubinemia). We used Cox regression to determine hazard ratios (HRs) with 95% confidence intervals (CIs) of endpoints among initiators of nucleos(t)ide analogue combinations, antiretroviral classes, and ART regimens, all stratified by viral hepatitis status.ResultsLiver aminotransferases >200 U/L developed in 206 (2%) persons and occurred more frequently among HIV/viral hepatitis-coinfected than HIV-monoinfected persons (116.1 vs 20.7 events/1000 person-years; P < .001). No evidence of differential risk was found between initiators of abacavir/lamivudine versus tenofovir/emtricitabine among coinfected (HR, 0.68; 95% CI, .29-1.57) or HIV-monoinfected (HR, 1.19; 95% CI, .47-2.97) groups. Coinfected patients had a higher risk of aminotransferases >200 U/L after initiation with a protease inhibitor than nonnucleoside reverse-transcriptase inhibitor (HR, 2.01; 95% CI, 1.36-2.96). Severe ALI (30 events; 0.3%) occurred more frequently in coinfected persons (15.9 vs 3.1 events/1000 person-years; P < .001) but was too uncommon to evaluate in adjusted analyses.ConclusionsWithin the year after ART initiation, aminotransferase elevations were infrequently observed and rarely led to severe ALI. Protease inhibitor use was associated with a higher risk of aminotransferase elevations among viral hepatitis-coinfected patients.

BackgroundHIV infection is independently associated with risk of lung cancer, but few data exist for the relation between longitudinal measurements of immune function and lung-cancer risk in people living with HIV.MethodsWe followed up participants with HIV from the Veterans Aging Cohort Study for a minimum of 3 years between Jan 1, 1998, and Dec 31, 2012, and used cancer registry data to identify incident cases of lung cancer. The index date for each patient was the later of the date HIV care began or Jan 1, 1998. We excluded patients with less than 3 years' follow-up, prevalent diagnoses of lung cancer, or incomplete laboratory data. We used Cox regression models to investigate the relation between different time-updated lagged and cumulative exposures (CD4 cell count, CD8 cell count, CD4/CD8 ratio, HIV RNA, and bacterial pneumonia) and risk of lung cancer. Models were adjusted for age, race or ethnicity, smoking, hepatitis C virus infection, alcohol use disorders, drug use disorders, and history of chronic obstructive pulmonary disease and occupational lung disease.FindingsWe identified 277 cases of incident lung cancer in 21 666 participants with HIV. In separate models for each time-updated 12 month lagged, 24 month simple moving average cumulative exposure, increased risk of lung cancer was associated with low CD4 cell count (p trend=0·001), low CD4/CD8 ratio (p trend=0·0001), high HIV RNA concentration (p=0·004), and more cumulative bacterial pneumonia episodes (12 month lag only; p trend=0·0004). In a mutually adjusted model including these factors, CD4/CD8 ratio and cumulative bacterial pneumonia episodes remained significant (p trends 0·003 and 0·004, respectively).InterpretationIn our large HIV cohort in the antiretroviral therapy era, we found evidence that dysfunctional immune activation and chronic inflammation contribute to the development of lung cancer in the setting of HIV infection. These findings could be used to target lung-cancer prevention measures to high-risk groups.FundingUS National Institutes of Health.

Background After adjustment for cardiovascular risk factors and despite higher mortality, those with human immunodeficiency virus (HIV+) have a greater risk of acute myocardial infarction (AMI) than uninfected individuals.Methods We included HIV+ individuals who started combination antiretroviral therapy (cART) in the Veterans Aging Cohort Study (VACS) from 1996 to 2012. We fit multivariable proportional hazards models for baseline, time-updated and cumulative measures of HIV-1 RNA, CD4 counts, and the VACS Index. We used the trapezoidal rule to build the following cumulative measures: viremia copy-years, CD4-years, and VACS Index score-years, captured 180 days after cART initiation until AMI, death, last clinic visit, or 30 September 2012. The primary outcomes were incident AMI (Medicaid, Medicare, and Veterans Affairs International Classification of Diseases-9 codes) and death.Results A total of 8168 HIV+ individuals (53 861 person-years) were analyzed with 196 incident AMIs and 1710 deaths. Controlling for known cardiovascular risk factors, 6 of the 9 metrics predicted AMI and all metrics predicted mortality. Time-updated VACS Index had the lowest Akaike information criterion among all models for both outcomes. A time-updated VACS Index score of 55+ was associated with a hazard ratio (HR) of 3.31 (95% confidence interval [CI], 2.11-5.20) for AMI and a HR of 31.77 (95% CI, 26.17-38.57) for mortality.Conclusions Time-updated VACS Index provided better AMI and mortality prediction than CD4 count and HIV-1 RNA, suggesting that current health determines risk more accurately than prior history and that risk assessment can be improved by biomarkers of organ injury.

ObjectivePractice guidelines recommend the shortest duration of antimicrobial therapy appropriate to treat uncomplicated pneumonia be prescribed to reduce the emergence of resistant pathogens. A national evaluation was conducted to assess the duration of therapy for pneumonia.DesignRetrospective medication utilization evaluation.SettingThirty Veterans Affairs medical centers.PatientsInpatients discharged with a diagnosis of pneumonia.MeasurementsA manual review of electronic medical records of inpatients discharged with uncomplicated community-acquired pneumonia (CAP) or healthcare-associated pneumonia (HCAP) was conducted. Appropriate CAP therapy duration was defined as at least 5 days, and up to 3 additional days beginning the first day the patient achieved clinical stability criteria; the appropriate HCAP therapy duration was defined as 8 days. The duration of antimicrobial therapy for intravenous (IV) and oral (PO) inpatient administration, PO therapy dispensed upon discharge, Clostridium difficile infection (CDI), hospital readmission, and death rates were measured.ResultsOf 3881 pneumonia admissions, 1739 met inclusion criteria (CAP [n = 1195]; HCAP [n = 544]). Overall, 13.9% of patients (CAP [6.9%], HCAP [29.0%]) received therapy duration consistent with guideline recommendations. The median (interquartile range) days of therapy were 4 days (3-6 days), 1 day (0-3 days), and 6 days (4-8 days) for inpatient IV, inpatient PO, and outpatient PO antimicrobials, respectively. CDI was rare but more common in patients who received therapy duration consistent with guidelines. Therapy duration was not associated with the readmission or mortality rate.ConclusionsAntimicrobials were commonly prescribed for a longer duration than guidelines recommend. The majority of excessive therapy was completed upon discharge, identifying the need for strategies to curtail unnecessary use postdischarge. Journal of Hospital Medicine 2015;11:832-839. © 2015 Society of Hospital Medicine.

Improved survival with combination antiretroviral therapy has led to a dramatic increase in the number of human immunodeficiency virus (HIV)-infected individuals 50 years of age or older such that by 2020 more than 50% of HIV-infected persons in the United States will be above this age. Recent studies confirm that antiretroviral therapy should be offered to all HIV-infected patients regardless of age, symptoms, CD4+ cell count, or HIV viral load. However, when compared with HIV-uninfected populations, even with suppression of measurable HIV replication, older individuals are at greater risk for cardiovascular disease, malignancies, liver disease, and other comorbidities.

ObjectiveUtilizing the Veterans Aging Cohort Study, the largest HIV cohort in North America, we conducted one of the few comprehensive comparisons of cancer incidence time trends in HIV-infected (HIV+) versus uninfected persons during the antiretroviral therapy (ART) era.DesignProspective cohort study.MethodsWe followed 44 787 HIV+ and 96 852 demographically matched uninfected persons during 1997-2012. We calculated age-, sex-, and race/ethnicity-standardized incidence rates and incidence rate ratios (IRR, HIV+ versus uninfected) over four calendar periods with incidence rate and IRR period trend P values for cancer groupings and specific cancer types.ResultsWe observed 3714 incident cancer diagnoses in HIV+ and 5760 in uninfected persons. The HIV+ all-cancer crude incidence rate increased between 1997-2000 and 2009-2012 (P trend = 0.0019). However, after standardization, we observed highly significant HIV+ incidence rate declines for all cancer (25% decline; P trend

BackgroundGuidelines now recommend limited use of routine CD4 cell count testing in human immunodeficiency virus (HIV)-infected patients with successful viral control who are not immunocompromised.MethodsCD4 and viral load tests for patients receiving HIV care from the US Department of Veterans Affairs during 2009-2013 were evaluated to determine trends in CD4 testing frequency and the number, cost, and results of CD4 tests considered optional under the guidelines.ResultsThere were 28 530 individuals with sufficient testing to be included. At the time of the last CD4 test, 19.8% of the cohort was eligible for optional monitoring and 15.6% for minimal monitoring. CD4 testing frequency declined by 10.8% over 4 years, reducing the direct cost of testing by US$196 000 per year. Full implementation of new treatment guidelines could reduce CD4 testing a further 28.9%, an additional annual savings of US$600 000. CD4 tests conducted during periods of potentially reduced monitoring were rarely

BACKGROUND Antimicrobial stewardship programs (ASPs) are variably implemented. OBJECTIVE To characterize variations of antimicrobial stewardship structure and practices across all inpatient Veterans Affairs facilities in 2012 and correlate key characteristics with antimicrobial usage. DESIGN A web-based survey regarding stewardship activities was administered to each facility's designated contact. Bivariate associations between facility characteristics and inpatient antimicrobial use during 2012 were determined. SETTING Total of 130 Veterans Affairs facilities with inpatient services. RESULTS Of 130 responding facilities, 29 (22%) had a formal policy establishing an ASP, and 12 (9%) had an approved ASP business plan. Antimicrobial stewardship teams were present in 49 facilities (38%); 34 teams included a clinical pharmacist with formal infectious diseases (ID) training. Stewardship activities varied across facilities, including development of yearly antibiograms (122 [94%]), formulary restrictions (120 [92%]), stop orders for antimicrobial duration (98 [75%]), and written clinical pathways for specific conditions (96 [74%]). Decreased antimicrobial usage was associated with having at least 1 full-time ID physician (P=.03), an ID fellowship program (P=.003), and a clinical pharmacist with formal ID training (P=.006) as well as frequency of systematic patient-level reviews of antimicrobial use (P=.01) and having a policy to address antimicrobial use in the context of Clostridium difficile infection (P=.01). Stop orders for antimicrobial duration were associated with increased use (P=.03). CONCLUSIONS ASP-related activities varied considerably. Decreased antibiotic use appeared related to ID presence and certain select practices. Further statistical assessments may help optimize antimicrobial practices. Infect Control Hosp Epidemiol 2016;37:647-654.

BACKGROUND:The Patient Protection and Affordable Care Act encourages healthcare systems to track quality-of-care measures; little is known about their impact on mortality rates. The objective of this study was to assess associations between HIV quality of care and mortality rates. METHODS:A longitudinal survival analysis of the Veterans Aging Cohort Study included 3038 human immunodeficiency virus (HIV)-infected patients enrolled between June 2002 and July 2008. The independent variable was receipt of ≥80% of 9 HIV quality indicators (QIs) abstracted from medical records in the 12 months after enrollment. Overall mortality rates through 2014 were assessed from the Veterans Health Administration, Medicare, and Social Security National Death Index records. We assessed associations between receiving ≥80% of HIV QIs and mortality rates using Kaplan-Meier survival analysis and adjusted Cox proportional hazards models. Results were stratified by unhealthy alcohol and illicit drug use. RESULTS:The majority of participants were male (97.5%) and black (66.8%), with a mean (standard deviation) age of 49.0 (8.8) years. Overall, 25.9% reported past-year unhealthy alcohol use and 28.4% reported past-year illicit drug use. During 24 805 person-years of follow-up (mean [standard deviation], 8.2 [3.3] years), those who received ≥80% of QIs experienced lower age-adjusted mortality rates (adjusted hazard ratio, 0.75; 95% confidence interval, .65-.86). Adjustment for disease severity attenuated the association. CONCLUSIONS:Receipt of ≥80% of select HIV QIs is associated with improved survival in a sample of predominantly male, black, HIV-infected patients but was insufficient to overcome adjustment for disease severity. Interventions to ensure high-quality care and address underlying chronic illness may improve survival in HIV-infected patients.