Inappropriate antibiotic selection &/or duration has been reported in 40–65% of patients treated in the Emergency Department (ED). Antimicrobial stewardship program (ASP) interventions in the ED are challenged by time constraints and diagnostic uncertainty. Most studies of ED antibiotic use rely on ICD-10 diagnostic codes, not clinical chart review.Figure 1.Patient DemographicsFigure 2.Appropriateness of Antibiotic SelectionPrevalence of Inappropriate Antibiotic Prescriptions Among US Ambulatory Care Visits, 2010-2011 | Infectious Diseases | JAMA | JAMA Network, Measurement and Evaluation Approaches to Improve Outpatient Antibiotic Prescribing in Health Systems We conducted a Medication Use Evaluation (MUE) at 40 Veterans Affairs facilities to assess oral antibiotic prescribing in ED & urgent settings. Objectives were to: 1) assess antibiotic prescribing using CDC diagnostic tiers—Tier 1 (almost always indicated), Tier 2 (sometimes indicated), & Tier 3 (rarely indicated); 2) determine the appropriateness of antibiotic selection and duration based on national guidelines; & 3) compare chart documentation with ICD-10 codes. Each site reviewed ∼100 eligible records using a standardized MUE protocol. Patients were included if they received an oral antibiotic prescription within 24 hours of an ED or urgent care visit from June 1, 2022 to May 31, 2023. Exclusions included receipt of antibiotics or hospitalization within 7 days prior to the encounter. MUE was determined as non-research by Hines IRB.Figure 3.Duration of Antibiotic Prescribing among Persons with Appropriate Antibiotic Selection Concordance of Clinical Notes and ICD-10 Diagnoses (%) Among 4575 Veterans included in the evaluation (Figure 1), clinician documentation indicated that 22%, 59% & 19% had Tier 1, 2 & 3 diagnoses, respectively. Appropriateness of antibiotic selection (Figure 2) was >80% except for sinusitis (73%) & pharyngitis (75%). Appropriateness of antibiotic duration (Figure 3) was 76% for pneumonia & < 65% for sinusitis, SSTIs, dental infections, and cystitis. Tier 3 durations often exceeded 5 days (Figure 2). Concordance between clinical notes and ICD-10 codes was poor (46%) across all tiers (Figure 4). Improving stewardship in EDs will benefit from multidisciplinary effort with engagement of ED practitioners, pharmacists & ASPs. This MUE highlights opportunities to reduce Tier 3 prescribing, develop standardized infection treatment guidelines, & improve documentation & coding accuracy. The high level of discordance between chart review & ICD-10 coded diagnoses underscores the challenges in using administrative data to assess antibiotic prescribing appropriateness. All Authors: No reported disclosures

Rationale:Controlled trials have demonstrated successful weight loss associated with certain weight management medications (WMMs). However, there are limited real-world data on prescribing patterns and efficacy and safety profiles of WMMs in Veterans Affairs (VA) patients. Objective:To evaluate: utilization patterns of WMMs liraglutide, naltrexone/bupropion, orlistat, phentermine, phentermine/topiramate, and semaglutide; weight loss at three, six, twelve, and more than 12 months; safety; and treatment barriers. Methods:A retrospective, cross-sectional medication use evaluation (MUE) was conducted using electronic health records of outpatient Veterans newly initiated on WMMs at 37 VA Medical Centers between 1 March 2020 and 31 March 2022. Chart review was used to identify WMM utilization and capture rates of clinical response, defined as 5% and 10% or greater weight loss at the final weight, adverse drug events (ADEs), non-adherence, and discontinuations. Site-specific surveys evaluated local practices and barriers. Results:Among 1959 eligible Veterans, semaglutide, phentermine/topiramate, and orlistat were most frequently prescribed. The clinical response was highest among phentermine/topiramate, liraglutide, and semaglutide. Naltrexone/bupropion and phentermine demonstrated the highest and lowest ADE rates, respectively. Potential barriers to WMM utilization and successful treatment by site reports were drug shortages, patient perceptions of therapeutic course, personal preferences, and VA WMM use criteria. Conclusions:Smaller weight loss and higher discontinuation rates were observed relative to clinical trials. The MUE data allow for better assessment of benefits and risks for Veterans prescribed WMMs.

ABSTRACT Little is known regarding the effectiveness of tixagevimab/cilgavimab in preventing SARS-CoV-2 infection in vaccinated immunocompromised patients, particularly after the emergence of the Omicron variant. In this retrospective cohort study with exact matching and propensity score adjustment within the U.S. Department of Veterans Affairs (VA) healthcare system, we selected immunocompromised veterans age ≥18 years as of 1 January 2022, receiving VA healthcare. We compared a cohort of 1,878 patients treated with at least one dose of intramuscular tixagevimab/cilgavimab to 7,014 matched controls selected from patients who met study criteria but were not treated. Patients were followed through 15 June 2022, or until death, whichever occurred earlier. The primary outcome was a composite of SARS-CoV-2 infection, COVID-19-related hospitalization, and all-cause mortality. We used Cox proportional hazards modeling to estimate the hazard ratios (HRs) and 95% CI for the association between receipt of tixagevimab/cilgavimab and outcomes. Most (73%) tixagevimab/cilgavimab recipients were ≥65 years old, and 80% had ≥3 mRNA vaccine doses or two doses of Ad26.COV2. Compared to matched controls, recipients had a lower incidence of the composite COVID-19 outcome (49/1,878 [2.6%] versus 312/7,014 [4.4%]; HR 0.35; 95% CI, 0.24–0.52), and individually SARS-CoV-2 infection (HR 0.44; 95% CI, 0.22–0.88), COVID-19 hospitalization (HR 0.24; 95% CI, 0.10–0.59), and all-cause mortality (HR 0.32; 95% CI, 0.19–0.55). In conclusion, tixagevimab/cilgavimab was associated with lower rates of SARS-CoV-2 infection and severe COVID-19 during the Omicron BA.1, BA.2, and BA.2.12.1 surge. IMPORTANCE SARS-CoV-2 remains an ongoing global health crisis that justifies continued efforts to validate and expand, when possible, knowledge on the efficacy of available vaccines and treatments. Clinical trials have been limited due to fast tracking of medications for mitigation of the COVID-19 pandemic for the general population. We present a real-world analysis, using electronic health record data, of the effectiveness of tixagevimab/cilgavimab for the prevention of COVID-19 infection in the unique population of U.S. veterans. Unlike those in the PROVENT clinical trial from which the emergency use authorization for tixagevimab/cilgavimab as a preventative treatment arose, the veterans population is highly immunocompromised and nearly 96% totally vaccinated. These demographics allowed us to analyze the effectiveness of tixagevimab/cilgavimab in preventing COVID-19 under different conditions in a more fragile population than that of the initial clinical trial.

PURPOSE:Early data suggest that mechanically ventilated COVID-infected (COVID+) patients had increased sedation requirements compared with historical controls.The impact of these sedation practices on patient-relevant clinical outcomes remains unknown.To evaluate this concern for increased sedative use, we conducted a quality improvement medication use evaluation (MUE) project to assess sedation practice patterns and observed outcomes for mechanically ventilated COVID+ Veterans in intensive care units (ICUs).Our results are from pilot chart review. METHODS:A multidisciplinary team comprised of senior VA Center for Medication Safety (VAMedSAFE) staff, critical care providers, clinical pharmacists, and statisticians collaborated on the design of this MUE to measure sedation practices and clinical outcomes during the COVID pandemic across the Veterans Health Administration.A total of 13 VA medical centers (VAMCs) completed data use agreements to conduct local chart reviews.Given potential practice variations over the course of the pandemic, three time periods were selected for review: pre-(3/2019-2/2020), COVID Year 1 (3/2020-2/2021), and COVID Year 2 (3/2021-3/ 2022).Each participating VAMC will screen at least 75 patients from each of the 3 time periods from their site (anticipated total patient charts screened n¼2925).Any ICU patient intubated for $2 calendar days will be eligible for analysis.Patients transferred from a non-VA facility, transferred out of the ICU within 48 hours of admission, or those intubated for >14 days will be excluded.Our primary outcomes include dose and duration of sedative exposure, hospital length of stay (LOS), new antipsychotic prescription, ileus, delirium, and overall mortality.Outcomes and covariates will be ascertained by structured data, when available, and validated by chart review.The MUE pilot was conducted from 1/2023-3/2023. RESULTS:The pilot identified challenges in operationalizing definitions for chart review.Among 83 patients from 11 participating sites, 49% met inclusion criteria.Most exclusions were due to ICU LOS restrictions in the initial MUE chart abstraction tool.As a result, we adapted the existing tool to restrict by intubation days >14 (vs.total ICU LOS).Our pilot also revealed wide variation in clinical pain assessment and spontaneous awakening trials.To maximize fidelity of these domains, we adapted the MUE to allow for open-ended and semi-structured responses. CONCLUSIONS:The MUE may inform opportunities to develop system-level medication use improvements at VAMCs.Understanding sedation use during high volume pandemic periods may also mitigate the strain from drug shortages in future respiratory pandemics.CLINICAL IMPLICATIONS: Formal assessment of prescribing practices and patient-relevant clinical outcomes via this MUE will help to guide creation and implementation of safer sedation guidelines within the VA healthcare system.

IntroductionAntibiotics and opioids are targeted by public health and stewardship communities for reductions in prescribing across the country. This study evaluates trends and factors associated with outpatient prescribing by dental and medical providers in a large integrated health system.MethodsThis was a cross-sectional study of national dental and medical outpatient visits from Department of Veterans Affairs facilities in 2015–2017; analyzed in 2019–2020. Antibiotic and opioid prescribing rates were assessed by provider and facility characteristics. Multivariable Poisson regression adjusted for repeated measures by the provider was used to assess the independent association between facility and provider characteristics and rate of prescribing.ResultsOver the study period, 4,625,840 antibiotic and 10,380,809 opioid prescriptions were identified for 115,625,890 visits. Physicians prescribed most antibiotics (67%). Dentists prescribed 6% of the antibiotics but had the highest per-visit antibiotic prescribing rate compared to medical providers (6.75 vs 3.90 prescriptions per 100 visits, p<0.0001), which was largely driven by dental specialists. By contrast, dentists had lower opioid prescribing than medical providers (3.02 vs 9.20 prescriptions per 100 visits, p<0.0001). Overall, antibiotic and opioid prescribing decreased over time, with opioids having the greatest decreases (−28.0%). In multivariable analyses, U.S. geographic region, rurality, and complexity were associated with prescribing for both drug classes. Opioid and antibiotic prescribing were positively correlated.ConclusionsAlthough antibiotic and opioid prescribing has decreased, there are still important target areas for improvement. Interventions need to be tailored to community characteristics such as rurality and provider type.

Background: Inappropriate use of MRSA-spectrum antibiotics is an important antimicrobial stewardship target. Contributors to inappropriate use include empiric treatment of patients who are determined to not be infected or who are infected but lack MRSA risk factors, and by excessive treatment duration when suspected MRSA infection is disproven. To characterize opportunities for improvement, we conducted a medical use evaluation (MUE) in 27 VA medical centers. The primary objectives were to assess the following proportions: (1) courses of unjustified empiric vancomycin therapy (patients in whom all antibacterials were halted within 2 days or without a principal or secondary discharge infection diagnosis); (2) courses of unjustified continuation of anti-MRSA therapy beyond day 4 (no MRSA risk factors or proven MRSA infection); and (3) excess anti-MRSA days of therapy (DOT), that is, DOT in unjustified empiric courses plus DOT after day 4 in unjustified continued courses. Methods: Clinical pharmacists performed retrospective, structured, manual record reviews of patients started on intravenous vancomycin on day 1 or 2 of hospitalization from June 2017 to May 2018. Exclusion criteria included surgical prophylaxis, recent MRSA infection, β-lactam allergy, renal insufficiency, severe immunosuppression, or infection that warranted anti-MRSA therapy other than vancomycin. Results: Of 2,493 evaluated patients, 1,320 met the inclusion criteria. Among them, 44% of courses were initiated in the emergency department, 37% of patients had ≥1 risk factor for healthcare-associated infections, and 50% of patients had ≥2 SIRS criteria or required vasopressor support. The most common admission diagnoses were skin and soft-tissue infection (SSTI, 40%; 68% nonpurulent) and pneumonia (27%; 46% without healthcare risk factors). Clinical cultures recovered MRSA from 8% of patients. Empiric therapy was not justified in 342 patients (26%; 57% were clinically stable). Continued therapy was unjustified in 46% of the 320 patients who received >4 days of anti-MRSA therapy. Of all days of anti-MRSA therapy, 23% were unjustified; 65% of these were due to unjustified empiric therapy. Site-specific variations in unjustified empiric therapy better correlated with the proportion of unjustified DOT than did unjustified continuation of therapy (Pearson correlation coefficients [PCC], 0.75 and 0.54, respectively) (Fig. 1). Facility-specific proportions of unjustified DOT modestly correlated with anti-MRSA DOT (PCC, 0.45; n = 27) (Fig. 2) but not the anti-MRSA standardized antimicrobial administration ratio (PCC, 0.15; n = 21). Conclusions: In this multicenter MUE, 26% of all days of anti-MRSA therapy lacked justification; this rate correlated with total facility-specific anti-MRSA DOT. Unnecessary empiric therapy, largely in the ED and for nonpurulent SSTIs and pneumonia without risk factors, was the principal contributor to unjustified DOT.Funding: NoneDisclosures: None

OBJECTIVE:Identifying drug discontinuation (DDC) events and understanding their reasons are important for medication management and drug safety surveillance. Structured data resources are often incomplete and lack reason information. In this article, we assessed the ability of natural language processing (NLP) systems to unlock DDC information from clinical narratives automatically.MATERIALS AND METHODS:We collected 1867 de-identified providers' notes from the University of Massachusetts Medical School hospital electronic health record system. Then 2 human experts chart reviewed those clinical notes to annotate DDC events and their reasons. Using the annotated data, we developed and evaluated NLP systems to automatically identify drug discontinuations and reasons at the sentence level using a novel semantic enrichment-based vector representation (SEVR) method for enhanced feature representation.RESULTS:Our SEVR-based NLP system achieved the best performance of 0.785 (AUC-ROC) for detecting discontinuation events and 0.745 (AUC-ROC) for identifying reasons when testing this highly imbalanced data, outperforming 2 state-of-the-art non-SEVR-based models. Compared with a rule-based baseline system for discontinuation detection, our system improved the sensitivity significantly (57.75% vs 18.31%, absolute value) while retaining a high specificity of 99.25%, leading to a significant improvement in AUC-ROC by 32.83% (absolute value).CONCLUSION:Experiments have shown that a high-performance NLP system can be developed to automatically identify DDCs and their reasons from providers' notes. The SEVR model effectively improved the system performance showing better generalization and robustness on unseen test data. Our work is an important step toward identifying reasons for drug discontinuation that will inform drug safety surveillance and pharmacovigilance.

IMPORTANCEUnlike warfarin, which requires routine laboratory testing and dose adjustment, target-specific oral anticoagulants like dabigatran do not. However, optimal follow-up infrastructure and modifiable site-level factors associated with improved adherence to dabigatran are unknown.OBJECTIVESTo assess site-level variation in dabigatran adherence and to identify site-level practices associated with higher dabigatran adherence.DESIGN, SETTING, AND PARTICIPANTSMixed-methods study involving retrospective quantitative and cross-sectional qualitative data. A total of 67 Veterans Health Administration sites with 20 or more patients filling dabigatran prescriptions between 2010 and 2012 for nonvalvular atrial fibrillation were sampled (4863 total patients; median, 51 patients per site). Forty-seven pharmacists from 41 eligible sites participated in the qualitative inquiry.EXPOSURESite-level practices identified included appropriate patient selection, pharmacist-driven patient education, and pharmacist-led adverse event and adherence monitoring.MAIN OUTCOMES AND MEASURESDabigatran adherence (intensity of drug use during therapy) defined by proportion of days covered (ratio of days supplied by prescription to follow-up duration) of 80% or more.RESULTSThe median proportion of patients adherent to dabigatran was 74% (interquartile range [IQR], 66%-80%). After multivariable adjustment, dabigatran adherence across sites varied by a median odds ratio of 1.57. Review of practices across participating sites showed that appropriate patient selection was performed at 31 sites, pharmacist-led education was provided at 30 sites, and pharmacist-led monitoring at 28 sites. The proportion of adherent patients was higher at sites performing appropriate selection (75% vs 69%), education (76% vs 66%), and monitoring (77% vs 65%). Following multivariable adjustment, association between pharmacist-led education and dabigatran adherence was not statistically significant (relative risk [RR], 0.94; 95% CI, 0.83-1.06). Appropriate patient selection (RR, 1.14; 95% CI, 1.05-1.25), and provision of pharmacist-led monitoring (RR, 1.25; 95% CI, 1.11-1.41) were associated with better patient adherence. Additionally, longer duration of monitoring and providing more intensive care to nonadherent patients in collaboration with the clinician improved adherence.CONCLUSIONS AND RELEVANCEAmong nonvalvular atrial fibrillation patients treated with dabigatran, there was variability in patient medication adherence across Veterans Health Administration sites. Specific pharmacist-based activities were associated with greater patient adherence to dabigatran.

Background: Patients on target specific anticoagulants (TSOACs) such as dabigatran do not require routine laboratory testing and dose adjustment. In the Veterans Health Administration (VHA), anticoagulation clinics (ACCs) may elect to follow and manage patients on TSOACs, but whether it is needed or the optimal duration of follow-up is unknown. Our objective was to assess the perspective of anticoagulation clinic providers on follow-up care for dabigatran patients and to identify site-level practices associated with improved adherence to dabigatran. Methods: We ascertained ACC providers’ perspectives through semi-structured interviews by a single, trained internist. Purposive sampling was utilized to recruit senior ACC providers or supervisors at VHA sites with over 20 patients on dabigatran. We stratified sites into high and low performing sites based on whether sites had ≥ 75% of their patients adherent, based on a proportion-of-days-covered calculation. Data from the interviews was analyzed by 2 reviewers in an iterative process to identify recurrent and unifying themes. Constant comparative method of qualitative data analysis was used to identify best practices across various sites. Results: We interviewed ACC providers from 39 sites - including 18 providers at 16 high-performing sites and 25 providers at 23 low-performing sites. Follow-up practices for dabigatran varied across sites, with 6 sites not providing any follow-up, 14 sites following-up patients for less than 3 months, 9 sites following-up patients for 6 months, and 10 sites following-up patients indefinitely. During these follow-up visits, patients were contacted at regular intervals, mostly via telephone, by ACC providers to provide education, assess side-effects and adherence. Key strategies implemented at high-performing sites compared to low-performing sites included (1) examining adherence to other twice daily medications prior to approving dabigatran (2) education of patients by ACC providers prior to dabigatran initiation (3) continued telephone follow up by ACC staff despite no need for INR checks. Over a third of ACC providers expressed concerns regarding patient adherence to dabigatran. Most common reasons for this concern included its special storage requirements and high incidence of gastrointestinal side effects leading to high discontinuation rates. Conclusion: Dedicated follow-up of patients on dabigatran is associated with improved adherence. A multi-disciplinary approach involving anti-coagulation clinic providers to provide education and follow-up may be beneficial in management of TSOACs. Future work should compare the apparent benefit of this strategy with its non-trivial cost.

Background Dabigatran is a novel oral anti-coagulant (NOAC) that reduces risk of stroke in patients with non-valvular atrial fibrillation (NVAF). It does not require routine monitoring with laboratory testing which may have an adverse impact on adherence. We aimed to describe adherence to dabigatran in the first year after initiation and assess the association between non-adherence to dabigatran and clinical outcomes in a large integrated healthcare system.Methods We studied a national cohort of 5,376 patients with NVAF, initiated on dabigatran between October-2010 and September-2012 at all Veterans Affairs hospitals. Adherence to dabigatran was calculated as proportion of days covered (PDC) and association between PDC and outcomes was assessed using standard regression techniques.Results Mean age of the study cohort was 71.3 +/- 9.7 years; 98.3% were men and mean CHADS(2) score was 2.4 +/- 1.2 (mean CHA(2)DS(2)VASc score 3.2 +/- 1.4). Median PDC was 94% (IQR 76%-100%; mean PDC 84% +/- 22%) over a median follow-up of 244 days (IQR 140-351). A total of 1,494 (27.8%) patients had a PDC <80% and were classified as non-adherent. After multivariable adjustment, lower adherence was associated with increased risk for combined all-cause mortality and stroke (HR 1.13, 95% CI 1.07-1.19 per 10% decrease in PDC). Adherence to dabigatran was not associated with non-fatal bleeding or myocardial infarction.Conclusions In the year after initiation, adherence to dabigatran for a majority of patients is very good. However, 28% of patients in our cohort had poor adherence. Furthermore, lower adherence to dabigatran was associated with increased adverse outcomes. Concerted efforts are needed to optimize adherence to NOACs.

Objectives To develop a list of prescription medications labelled with warnings for adverse effects of suicidal ideation or behaviour and to describe utilization in the USA and in the Department of Veterans Affairs (VA) in 2009.Methods A systematic search of US Food and Drug Administration and other references using 'suicide', 'suicidal' and 'suicidality' was used to identify prescription drugs labelled for risk of suicidal ideation or behaviour. Prescription medications sold in the USA by sales volume are reported alongside VA utilization as determined from national electronic pharmacy records.Key findings One hundred and twenty-five prescription drugs were labelled for potential adverse effects of suicidal ideation or behaviour. Forty-five of these drugs were among the top 200 prescription medications sold in the USA in 2009 with a total sales volume of 540.8 million prescriptions. Rank-ordered utilization was similar in the VA. VA total fill volume was 5.99 million prescriptions.Conclusions The majority of prescriptions with adverse effect warnings of suicidal ideation or behaviour were generic. Relatively high volumes of drugs with warnings for suicidal ideation or behaviour are filled in the USA and in the VA.