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.OBJECTIVE To 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.EXPOSURES Empirical anti-MRSA therapy plus standard pneumonia therapy vs standard therapy alone within the first day of hospitalization.MAIN OUTCOMES AND MEASURES Risk 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. RESULTS Among 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 RELEVANCE This study suggests that empirical anti-MRSA th...

Objective.Limited evidence exists comparing the persistence, effectiveness, and costs of biologic therapies for rheumatoid arthritis in clinical practice. Comparative effectiveness studies are needed to understand real-world experience with these agents. We evaluated treatment patterns, costs, and effectiveness of tumor necrosis factor inhibitor (TNFi) agents in patients enrolled in the Veterans Affairs Rheumatoid Arthritis (VARA) registry.Methods.Observational data from the VARA registry and linked administrative databases were analyzed. Longitudinal data from VARA patients initiating adalimumab (ADA), etanercept (ETN), or infliximab (IFX) from 2003 (the date all agents were available within the Veteran Affairs) to 2010 were analyzed. Outcomes included Disease Activity Score using 28 joints (DAS28), treatment persistence, dose escalation, and direct costs of drugs and drug administration.Results.For 563 eligible patients, baseline DAS28, DAS28 improvements, and persistence on initial treatment were similar across agents. Fewer patients receiving ETN (n = 5/290; 2%) underwent dose escalation than did patients taking ADA (n = 32/204; 16%) or IFX (n = 44/69; 64%). Annual costs for first course of TNFi therapy were lower for injectable ADA ($13,100 US) and ETN ($13,500 US) than for intravenously administered IFX ($16,900 US).Conclusion.Despite similar persistence and clinical disease activity for these TNFi agents, rates of dose escalation were highest with ADA and IFX. Higher overall costs were noted for IFX without increases in effectiveness.

BACKGROUND Electronic health records (EHR) provide the opportunity to assess system-wide quality measures. Veterans Affairs (VA) Pharmacy Benefits Management Center for Medication Safety employs Medication Use Evaluation (MUE) through manual review of the EHR. 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 VA 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 2,004 hospitalizations, electronic and manual abstraction methods demonstrated high individual hospitalization-level agreement for initial severity measures (agreement=86–98%, kappa=0.5–0.82), antibiotic choice (agreement=89–100%, kappa=0.70–0.94), and facility-level consistency for empiric antibiotic choice (anti-MRSA r=0.97, p<0.001; anti-pseudomonal 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 demonstrated 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.

Objective Low body mass index (BMI) is a risk factor for poor longterm outcomes in rheumatoid arthritis (RA). The purpose of this study was to identify factors associated with longterm changes in BMI. Methods Subjects with RA from the Veterans Affairs (VA) Rheumatoid Arthritis (VARA) Registry (n = 1474) were studied. Information on inflammatory markers, presence of erosions, and smoking status were extracted from the VARA database. BMI was extracted from VA electronic medical records within 14 days of each visit date. VA pharmacy records were queried to identify prescriptions for specific RA therapies within 1 month of the visit date. We used robust generalized estimating equations marginal regression models to calculate independent associations between clinical variables and BMI over time. Similar models determined predictors of change in weight and risk of weight loss over the subsequent study observation period. Results Increasing age, active smoking, and the presence of erosions at baseline were associated with lower BMI. Weight decreased over time among older adults. Factors associated with greater reductions in BMI over time and a greater risk of weight loss were higher inflammatory markers, smoking, older age, higher BMI, and less subsequent improvement in inflammation. Methotrexate use was associated with a lower risk of weight loss. The use of prednisone or anti-tumor necrosis factor therapies was not associated with change in BMI or the risk of weight loss independent of other factors. Conclusion Greater age, greater inflammatory activity, and active smoking are associated with greater weight loss in RA over time.

IntroductionThe purpose of this study was to evaluate clinical outcomes and drug/administration costs of treatment with tumor necrosis factor inhibitor (TNFi) agents in US veterans with rheumatoid arthritis (RA) initiating TNFi therapy. The analysis compared patients initiating and continuing a single TNFi with patients who subsequently switched to a different TNFi.MethodsData from patients enrolled in the Veterans Affairs Rheumatoid Arthritis (VARA) registry who initiated treatment with adalimumab, etanercept, or infliximab from 2003 to 2010 were analyzed. Outcomes included duration of therapy, Disease Activity Score based on 28 joints (DAS28), and direct drug and drug administration costs.ResultsOf 563 eligible patients, 262 initiated a single TNFi therapy, 142 restarted their initial TNFi after a ≥90-day gap in treatment (interrupted therapy), and 159 switched to a different TNFi. Patients who switched had higher mean DAS28 before starting TNFi therapy than patients with single or interrupted therapy: 5.3 vs 4.5 or 4.6, respectively. Mean duration of the first course was 34.3 months for single therapy, 18.3 months for interrupted therapy, and 17.7 months for switched therapy. Mean post-treatment DAS28 was highest for patients who switched TNFi. Mean annualized costs for first course were $13,800 for single therapy, $13,200 for interrupted therapy, and $14,200 for switched therapy; mean annualized costs for second course were $12,800 for interrupted therapy and $15,100 for switched therapy.ConclusionPatients who switched TNFi had higher pre-treatment DAS28 and higher overall costs than patients who received the same TNFi as either single or interrupted therapy.FundingThis research was funded by Immunex Corp., a fully owned subsidiary of Amgen Inc., and by VA HSR&D Grant SHP 08-172.