VA Pharmacy Research Articles

The association of azole antifungals with overall survival in patients with non-small cell lung cancer receiving immune checkpoint inhibitors.

Preclinical data suggest antifungal azole derivatives have antitumor efficacy that may modulate response to immune checkpoint inhibitors (ICIs). We aimed to evaluate the association of azole drugs with overall survival (OS) in a population of patients with non-small cell lung cancer (NSCLC) treated with ICI within the Veterans Health Administration (VHA). In this retrospective study, the VA Corporate Data Warehouse was queried for patients diagnosed with NSCLC and treated with ICI from 2010 to 2018. Concomitant oral azole use was defined as dispensation by a VA pharmacy within 90 days of the first ICI infusion. Patients who received azole after 30 days were excluded from the analysis to mitigate immortal time bias. OS was measured from the start of ICI. Cox regression and propensity score matching were used to adjust for confounders. We identified 3413 patients with NSCLC receiving ICI; 324 (9.5%) were exposed to concomitant azoles. As a group, azole use was not associated with OS (hazard ratio [HR] = 0.96; 95% CI, 0.84-1.09; P = .51). After stratification by azole type, clotrimazole had an association with better OS on univariable (HR = 0.75; 95% CI, 0.59-0.96; P = .024) and multivariable analysis (HR = 0.71; 95% CI, 0.56-0.91; P = .007). Propensity score matching of patients who received clotrimazole vs no azole yielded 101 patients per matched cohort. Clotrimazole was associated with improved OS, although this did not meet the threshold for statistical significance (HR = 0.74; 0.54-1.01; P = .058). This observational study demonstrated an association between clotrimazole and OS among patients with advanced NSCLC receiving ICI. These findings build upon preclinical evidence and support further investigation into the potential for clotrimazole as a repurposed FDA drug to improve cancer outcomes.

Demographic Characteristics and Treatment Patterns in Veterans with Multiple Myeloma: A Comprehensive Analysis from the Veterans Affairs Database (2000-2020)

BACKGROUND: Multiple Myeloma (MM) is the 2nd most common hematologic malignancy, accounting for 32,270 new cases diagnosed in the United States each year with over 12,830 deaths and a 57% overall 5 -year survival rate. Increased incidence is seen in patients aged >60, African American (AA) race and Male population. Despite significant advancements in therapies with novel agents and immunotherapy, MM remains a challenging disease to manage due to its heterogeneity, resistance to treatment, and the risk of relapse. In this study, we aim to determine the demographics, comorbidities and trends in treatment patterns of MM patients, over time in the VA database. METHODS: Patients diagnosed with MM from 2000-2020 in the VA's nationwide electronic health records were identified using the VA Corporate Data Warehouse (VA CDW) and VINCI to host and analyze the data. Patients were identified using International Classification of Diseases codes for MM. Patient demographics, including drugs and therapies used, were identified through structured data in the VA CDW. We included all veterans 1) over the age of 18, 2) diagnosed with MM with 3 coded visits on different days and received 1 agent other than steroids after diagnosis date. We excluded all patients who did not have at least two VA primary care visits, or one primary care visit and one VA pharmacy refill in the one year prior to MM diagnosis. We analyzed demographic details, comorbidity burden, treatment regimens for induction and attrition rates. RESULTS: A total of 12,196 patients were identified, with a median age at diagnosis of 68 years (range, 28-96 years), of which 97.8% were males, 59% (n=7187) were White, 23% (n=2903) were Black, Other (Asian/Pacific Islanders) made up 1.9% the cohort (n=233) and for 15% cohort (n=1867), race was either unknown or missing. Comorbidities at diagnosis were the following: 4164 patients had diabetes mellitus; 1329 patients had CHF ,2159 patients had pre-existing renal disease. 10,156 patients received at least one line of therapy, with the following distribution: 215 pts - RVD, 20 - DRD, 344 - CyBORD , 1930 - oral Melphalan, 3368- Thalidomide, 2692 -Revlimid/Dexamethasone, 1555 - Velcade/Dexamethasone and 2040 patients received an induction regimen not specified in Table 2. The breakdown of first line therapy utilization in respect to race is shown in Table 2. 4228 patients received two distinct lines of therapy (LOT), 1718 patients received 3 distinct LOT and 419 patients received 4 LOT. Transitioning from 1st st to 2nd LOT, attrition rates of approximately 50.3% for Black and 56.5% for White patients were observed, and from two to three lines, rates were around 52.4% for Black and 57.8% for White patients, indicating substantial drop-offs in treatment progression. The Cox proportional hazard model analysis reveals significant predictors for overall survival. Notably, age (70 or older) and renal disease was associated with increased mortality with hazard ratios (HR) of 1.731 and 1.275 (p < .0001 for both), respectively. Conversely, Black and White races, and receiving three or more therapy lines, was associated with increased OS, with HRs of 0.545, 0.607, and 0.825 (p < .0001 for all). CONCLUSIONS: This comprehensive overview of veterans with MM in the VA system over a 20-year period reveals heterogeneity in treatment utilization as expected with the changing landscape of MM treatment. A detailed analysis on the nature of subsequent lines of therapies, including stem cell transplant utilization, access to clinical trials is ongoing and will be submitted as a full manuscript publication. Additionally, the data on the staging and cytogenetics is also being obtained.

Zellmer lecturer spotlights VA pharmacy advancement initiatives.

Zellmer lecturer spotlights VA pharmacy advancement initiatives.

Patterns of psychotropic drug use in veterans with epilepsy: Do drug interactions matter?

RationalePatients with epilepsy are likely to suffer from psychiatric comorbidities, including depression and anxiety. They often require treatment with multiple psychotropic drugs (PDs). While it is clear that CYP-inducing ASMs (EIASMs) can increase the oral clearance of multiple medications (thus lowering systemic exposure), it is less clear that all PK interactions are clinically meaningful (e.g. lower efficacy). As a first step in addressing this issue, this study sought to quantify the potential impact of ASM choice, whether EIASM or non-inducer (NIASM), on surrogate markers of suggestive of clinical use, including resultant antidepressant (AD) or antipsychotic (AP) dose, frequency of combination use of AD & AP, and number of multiple drug switches of PDs. Our hypothesis is that because of PK interactions, EIAED treatment would be associated with higher psychotropic drug doses, more frequent Rx adjustments and poly psychotropic comedication, all in order to optimize therapeutic response. MethodsUsing VA pharmacy and national encounter databases, veterans with epilepsy were identified based on having a seizure diagnosis and being prescribed concomitantly an ASM and a psychotropic drug for at least 365 days between 10/1/2010 and 9/30/2014. Patients for whom psychotropic drugs were prescribed any time between beginning and end prescriptions dates of ASMs were considered. Among those, patients receiving both an EIASM + NEIASM concomitantly were categorized with the EIASM group. Patients were evaluated for AD only, AP only and both (AD & AP). To compute average drug doses per day, averages for each patient were computed and averaged again. Multiple drug switches were defined to be for patients who had been prescribed more than three psychotropic drugs during the observation period. Pearson’s Chi-Square test was used to compare relative proportions of AD, AP and AD + AP in both groups. ResultsIn all, 16,188 patients were identified (57.0% on EIASM, 43.0% on NIASM) with a mean age of 58.7 years (91.2% male). A larger proportion of patients on EIASM received mono treatment with any psychotropic drug, as compared to NIASM (42.0% vs 36.1%). Among all, 59.6% received AD only, 6.5% received AP only, and 33.8% received both concurrently. Of EIASM, 62.5% were on AD, 5.9% on AP, and 31.7% on both AP & AD. For NIASM, 55.9% received AD, 7.4% AP, and 36.7% on AD & AP.Chi-square showed that the distribution of PD was statistically different between EIASM and NIASM groups. Z tests showed that each difference (AD, AP and both) in proportions was statistically significant (p values (4 tests, one Chi-square, 3 Z tests <0.001) between EIASM vs NIASM. Interestingly, mean doses of AD or AP did not appear to differ between ASM groups. ConclusionsConcurrent psychotropic drug use is quite common in the VA population with epilepsy, and a large number of patients still receive enzyme-inducing ASMs that may complicate other medical therapies. Interestingly, in seeming contradiction to our hypothesis, mean daily doses of either AD or AP did not appear to differ between inducers vs non-inducers. Similarly, use of polytherapy, and/or multiple trials of various psychotropic drugs did not appear increased in the CYP-induced group. In fact, combination therapy of AD + AP was higher in NIASM than EIASM. These data suggest that perhaps these types of PK interactions may not in fact result in meaningful clinical differences. Since the present analyses did not include clinical psychiatric measures, future analyses examining direct clinical outcomes are clearly warranted.

The Association of Improved Overall Survival with NSAIDs in Non–Small Cell Lung Cancer Patients Receiving Immune Checkpoint Inhibitors

BackgroundImmune checkpoint inhibitors (ICI) are commonly used in the management of patients with advanced non-small cell lung cancer (NSCLC), but response is suboptimal. Preclinical data suggest ICI efficacy may be enhanced with concomitant nonsteroidal anti-inflammatory (NSAID) medications. Patients and MethodsIn this retrospective study, the Veterans Health Administration Corporate Data Warehouse was queried for patients diagnosed with NSCLC and treated with ICI from 2010 to 2018. Concomitant NSAID use was defined as NSAID dispensation by a VA pharmacy within 90 days of the any ICI infusion. To mitigate immortal time bias, patients who started NSAIDs 60 or more days after ICI initiation were excluded from analysis. Survival was measured from start of ICI. ResultsWe identified 3634 patients with NSCLC receiving ICI; 2336 (64.3%) were exposed to concomitant NSAIDs. On multivariable analysis, NSAIDs were associated with better overall survival (HR = 0.90; 95% CI, 0.83-0.98; P = .010). When stratifying by NSAID type, diclofenac was the only NSAID with significant association with overall survival (HR = 0.75; 95% CI, 0.68-0.83; P < .001). Propensity score matching of the original cohort yielded 1251 patients per cohort balanced in characteristics. NSAIDs remained associated with improved overall survival (HR = 0.85; 95% CI, 0.78-0.92; P < .001). ConclusionThis study of Veterans with NSCLC treated with ICI demonstrated that concomitant NSAIDs are associated with longer OS. This may indicate that NSAIDs can enhance ICI-induced antitumor immunity and should prospectively validated.

Complex pain phenotypes: Suicidal ideation and attempt through latent multimorbidity.

Given the relatively high rates of suicidal ideation and attempt among people with chronic pain, there is a need to understand the underlying factors to target suicide prevention efforts. To date, no study has examined the association between pain phenotypes and suicide related behaviors among those with mild traumatic brain injuries. To determine if pain phenotypes were independently associated with suicidal ideation / attempt or if comorbidities within the pain phenotypes account for the association between pain phenotypes and suicide related behaviors. This is a longitudinal retrospective cohort study of suicide ideation/attempts among pain phenotypes previously derived using general mixture latent variable models of the joint distribution of repeated measures of pain scores and pain medications/treatment. We used national VA inpatient, outpatient, and pharmacy data files for Post-9/11 Veterans with mild traumatic injury who entered VA care between fiscal years (FY) 2007 and 2009. We considered a counterfactual causal modeling framework to assess the extent that the pain phenotypes during years 1-5 of VA care were predictive of suicide ideation/attempt during years 6-8 of VA care conditioned on covariates being balanced between pain phenotypes. Without adjustment, pain phenotypes were significant predictors of suicide related behaviors. When we used propensity scores to balance the comorbidities present in the pain phenotypes, the pain phenotypes were no longer significantly associated with suicide related behaviors. These findings suggest that suicide ideation/attempt is associated with pain trajectories primarily through latent multimorbidity. Therefore, it is critical to identify and manage comorbidities (e.g., depression, post-traumatic stress disorder) to prevent tragic outcomes associated with suicide related behaviors throughout the course of chronic pain and mild traumatic brain injury management.

Abstract 12811: Dual Antiplatelet Therapy Duration and Long-Term Risks of Adverse Outcomes After Percutaneous Coronary Intervention With Second-Generation Drug-Eluting Stents

Introduction: Randomized trials show that short dual antiplatelet (DAPT) regimens have similar adverse events to longer regimens in patients treated by percutaneous coronary intervention (PCI) using second-generation drug-eluting stents (DES2). However, these studies are underpowered for death. Hypothesis: After PCI with DES2, patients discontinuing DAPT before six months had higher risks of adverse ischemic outcomes than patients continuing DAPT for longer durations. Methods: We assessed adverse outcomes in patients having PCI between 2008-2016 in the Veterans Affairs Clinical Assessment Report and Tracking (CART) database. DAPT use was determined from the VA Pharmacy database. Outcomes after PCI were all-cause death (from the VA death index), and myocardial infarction, recurrent coronary revascularization, and major bleeding from ICD 9, ICD 10 and CPT codes in VA and Medicare/Medicaid records. Hazard ratios (HR) and 95% confidence intervals (95%CI) from Cox proportional hazards models weighted with a stabilized inverse probability of treatment weight were used to assess the risk of outcomes from stopping DAPT in 4 time intervals after PCI (1-5, 6-9, 10-12, and 13-18 months). Results: After exclusions, there were 40,871 PCIs with DES2 during the study period. Outcomes were followed for an average of 4.6 years. Compared to continuing DAPT, the risks for death were significantly higher for stopping DAPT 1-5 months after PCI (HR=2.04, 95%CI=1.82, 2.29) and stopping DAPT 6-9 months after PCI (HR=2.2, 95%CI=1.98, 2.44). There was no significant increase in death from stopping DAPT more than 10 months after PCI. Stopping DAPT 10 or more months after the index PCI associated with lower rates of myocardial infarction (HR=0.74, 95%CI=0.68, 0.81) and major bleeding (HR=0.81, 95%CI 0.73, 0.91), and lower repeat revascularization at all time periods. There was no interaction of effects with acute coronary syndrome at index PCI. Conclusion: Among Veterans having PCI with DES2, stopping DAPT less than 10 months after PCI was associated with a higher risk of death but no increased risk in myocardial infarction or major bleeding. Short DAPT regimens after PCI may increase the risk of death. Clinical trials of short DAPT duration should powered to assess this endpoint.

Economics of Traumatic Brain Injury (TBI) Biomarkers

<h3>Research Objectives</h3> To investigate the annual utilization, unit and per veteran Veterans Health Administration (VHA) costs of CT and MRI in U.S. veterans with Traumatic Brain Injury (TBI), by TBI severity. To also examine the marginal impact of CT and MRI use on total, inpatient, outpatient and pharmacy (VHA) cost of veterans diagnosed with TBI. <h3>Design</h3> All VHA using veterans diagnosed with TBI between 2000-2010 and followed until 2014. <h3>Setting</h3> VHA Medical Centers and Community Based Outpatient Clinics. <h3>Participants</h3> 79,276 veterans identified with a TBI diagnosis. <h3>Interventions</h3> Logit models were used to predict the utilization of any CT or MRI, Poisson models for number of CT and MRI and generalized linear as well as seemingly unrelated regression models for annual VA inpatient, outpatient and pharmacy costs in 2018 dollars. All models were adjusted for TBI severity as well as comorbidities. <h3>Main Outcome Measures</h3> VHA CT and MRI utilization and VHA inpatient, outpatient and pharmacy costs. <h3>Results</h3> 84.78% of all veterans with TBI had CT and 61.29% had MRI. The mean ($468), median ($422) cost per unit for CT was lower than MRI mean ($732), median ($639). The odds (1.43; 95% CI 1.37:1.49) of CT increased with higher TBI severity and declined for MRI (0.68; 95% CI 0.66:0.71). The marginal effect of CT use was $1,775 (95% CI $1,514:$2,035) on annual total, $1,646 (95% CI $1,529:$1,763) on outpatient, and $373 (95% CI $315:$431) on pharmacy cost per veteran. The marginal effect of any MRI use was $851 (95% CI $582:$1,120) on total, -$1,522 (95% CI -$1,742:-$1,302) on inpatient cost, $1,983 (95% CI $1,899:$2,067) on outpatient, and $389 (95% CI $348:$431) on pharmacy cost. <h3>Conclusions</h3> MRI use was associated with a significant reduction in annual inpatient costs per veteran, even though its cost per unit was higher than CT. <h3>Author(s) Disclosures</h3> This material is based upon work supported by the U.S. Army Medical Research and Materiel Command and from the U.S. Department of Veterans Affairs Long-Term Impact of Military-Relevant Brain Injury Consortium (LIMBIC) Award No. l01 HX003155.

Management of Pseudomonas aeruginosa Bloodstream Infection and Impact on Health Outcomes

Background: Gram-negative bacteria cause a variety of hospital-associated infections (HAIs). Of concern is Pseudomonas aeruginosa, which is a leading cause of HAIs. Early and adequate therapy of P. aeruginosa blood stream infection (BSI) is associated with decreased mortality. Additionally, infectious disease consultation has also shown to improve health outcomes, streamline care, and decrease costs. Therefore, the goal of this study was to describe treatment of P. aeruginosa BSI and impact of infectious disease consultations on health outcomes. Methods: In this retrospective cohort study, we analyzed national VA medical, encounter, pharmacy, microbiology, and laboratory data from January 1, 2012 to December 31, 2018. The cohort included all hospitalized adult veterans (aged ≥18 years) who had a positive blood culture for P. aeruginosa. Only the first P. aeruginosa blood culture per patient was included, and duplicate cultures within 30 days were removed. Treatment was identified within −2 to +5 days of the culture date. Multidrug-resistant (MDR) cultures were identified based on resistance to at least 1 agent in at least 3 or more antimicrobial categories tested. Multivariable logistic regression models were fit to assess infectious disease consultations and adequate treatment on in-hospital mortality and 30-day mortality. Results: In total, 3,256 patients had a BSI with P. aeruginosa, of which 386 (11.5%) were MDR. Most of these patients were male (97.5%), &gt;65 years of age (70.9%), and non-Hispanic white (63.8%). Also, 784 patients (23.3%) died during hospitalization and 870 (25.8%) died within 30 days of their culture. In multivariable regression models, infectious disease consultations were associated with decreased odds of in-hospital mortality (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.53–0.77) and 30-day mortality (OR, 0.56, 95% CI, 0.48–0.67) even after adjusting for age, race, care setting, Charlson score, and prior healthcare exposures. Furthermore, inadequate definitive treatment was associated with increased odds of in-hospital mortality (OR, 2.77; 95% CI, 1.35–5.69) and 30-day mortality (OR, 2.37; 95% CI, 1.18–4.79), even after adjusting for age, Charlson score, care setting, and prior healthcare exposures. In addition, carbapenem treatment was associated with increased odds of in-hospital mortality (OR, 1.38; 95% CI, 1.12–1.70) and 30-day mortality (OR, 1.49; 95% CI, 1.22–1.81), whereas fluoroquinolone treatment was associated with lower odds of in-hospital mortality (OR, 0.49; 95% CI, 0.41–0.59) and 30-day mortality (OR, 0.60; 95% CI, 0.50–0.71). Finally, extended-spectrum cephalosporin was also associated with lower odds of in-hospital mortality (OR, 0.82; 95% CI, 0.68–0.98). Conclusions: Use of infectious disease consultations and any adequate definitive treatment for those with P. aeruginosa BSI lowered odds of in-hospital and 30-day mortality. Early consultation with infectious disease physicians regarding adequate treatment has direct positive impact on clinical outcomes for patients with P. aeruginosa BSI.Funding: NoDisclosures: None

Association of concomitant NSAID and immunotherapy on outcomes in patients with non-small cell lung cancer: Analysis of the National Veterans Health Administration Database.

9107 Background: Preclinical data suggests the efficacy of immune checkpoint inhibitors (ICI) may be enhanced with concomitant nonsteroidal anti-inflammatory (NSAID) medications. Real-world evidence to support investigating this hypothesis in prospective randomized trials are needed. Methods: A retrospective cohort study queried the VA Corporate Data Warehouse (VA-CDW) to identify patients diagnosed with NSCLC who were treated with ICI between 2010-18. Exposure to concomitant NSAID was determined whenever NSAID prescriptions were released from the VA pharmacy within 90 days of the first ICI infusion. Chi-square and ANOVA tests were used to compare baseline characteristics. The outcome of overall survival (OS) was measured from the start of ICI. Cox proportional hazard regression was used to adjust for demographic, clinical, tumor, and treatment characteristics. Results: The study cohort consisted of 3,415 patients with NSCLC treated with ICI, and 2,336 (64%) were exposed to concomitant NSAID. The median age was 69, male 97%, race: white 73%, black 21%, and 66% lived in urban areas. Most patients were initially diagnosed with stage III or IV disease (68%); tumor histology: adenocarcinoma 48% and squamous cell 38%. Comorbidity counts were 0 in 40%, 1-3 in 30%, and 4+ in 30%. Chemotherapy was delivered before ICI in 54% and concurrently with ICI in 31%. The most commonly used NSAIDs were aspirin (35%), ketorolac (11%), and ibuprofen (7%); 44% were exposed to more than one NSAID. With a median follow-up of 8 months, exposure to concomitant NSAIDs was associated with a longer OS (HR = 0.90; 0.83-0.98, p = 0.01) after adjusting for all available potential confounders on multivariable analyses. Longer OS persisted following propensity score matching (HR = 0.89; 0.82-0.97 p = 0.007). Other factors significant for OS on multivariable testing included use of chemotherapy after ICI (HR = 0.53 [0.40-0.69], p &lt; 0.001), concurrent chemotherapy during ICI (HR = 0.68 [0.62-0.74], p &lt; 0.001), younger age, black race, female gender, and adenocarcinoma histology. Among the various NSAIDs analyzed on the multivariable analyses, only diclofenac approached statistical significance (HR = 0.78 [0.59-1.03], p = 0.08). Limiting the comparison to patients exposed to diclofenac (n = 101) versus no NSAIDs (n = 1,298), the comparison demonstrated a similar trend for OS (HR = 0.79 [0.60-1.04], p = 0.094), although the association was attenuated after propensity-score matching (HR = 0.90 [0.63-1.29], p = 0.57). Conclusions: This retrospective cohort study of Veterans with NSCLC who were treated with ICI identified that concomitant receipt of NSAIDs is associated with longer OS.

Eligibility for Low-Dose Rivaroxaban Based on the COMPASS Trial: Insights from the Veterans Affairs Healthcare System.

Low-dose rivaroxaban reduced major adverse cardiac and limb events among patients with stable atherosclerotic vascular disease (ASCVD) in the COMPASS trial. The objective of our study was to evaluate the eligibility and budgetary impact of the COMPASS trial in a real-world population. The VA administrative and clinical databases were utilized to conduct a cross-sectional study to identify patients eligible for low-dose rivaroxaban receiving care at all 141 facilities between October 1, 2014 and September 30, 2015. Proportion of patients with stable ASCVD eligible for low-dose rivaroxaban and prevalence of multiple risk enrichment criteria among eligible patients. Pharmaceutical budgetary impact using VA pharmacy pricing. Chi-squared and Student's t tests were used to compare patients eligible versus ineligible patients. From an initial cohort of 1,248,214 patients with ASCVD, 488,495 patients (39.1%) met trial eligibility criteria. Eligible patients were older (74.2 vs 64.5years) with higher proportion of hypertension (84.1% vs 82.1%) and diabetes (46.2% vs 32.9) compared with ineligible patients (p < 0.001 for all comparisons). A median of 38.7% (IQR 4.6%) of total ASCVD patients per facility were rivaroxaban eligible. Estimated annual VA pharmacy budgetary impact would range from $0.47 billion to $1.88 billion for 25% to 100% treatment penetration. Annual facility level pharmaceutical budgetary impact would be a median of $12.3 million (IQR $8.0-$16.3 million) for treatment of all eligible patients. Among eligible patients, age greater than 65years was the most common risk enrichment factor (86.9%). Prevalence of eligible patients with multiple enrichment factors varied from 34.2% (one factor) to 6.2% (four or more). Over one third of patients with stable ASCVD may qualify for low-dose rivaroxaban within the VA. Additional studies are needed to understand eligibility in other populations and a formal cost-effectiveness analysis is warranted.

Managing Functional Neurological Disorders: Protocol of a Cohort Study on Psychogenic Non-Epileptic Seizures Study.

BackgroundFunctional neurological disorders (FNDs) are neurological symptoms that cannot be explained by an underlying neurological lesion or other medical illness and that do not have clear neuropathological correlates. Psychogenic non-epileptic seizures (PNES) are a common and highly disabling form of FND, characterized by paroxysmal episodes of involuntary movements and altered consciousness that can appear clinically similar to epileptic seizures. PNES are unique among FNDs in that they are diagnosed by video electroencephalographic (VEEG), a well-established biomarker for the disorder. The course of illness and response to treatment of PNES remain controversial. This study aims to describe the epidemiology of PNES in the Department of Veterans Affairs Healthcare System (VA), evaluate outcomes of veterans offered different treatments, and compare models of care for PNES.MethodsThis electronic health record (EHR) cohort study utilizes an informatics search tool and a natural language processing algorithm to identify cases of PNES nationally. We will use VA inpatient, outpatient, pharmacy, and chart abstraction data across all 170 medical centers to identify cases in fiscal years 2002–2018. Outcome measurements such as seizure frequency, emergency room visits, hospital admissions, suicide-related behavior, and the utilization of psychotherapy prior to and after PNES diagnosis will be used to assess the effectiveness of models of care.DiscussionThis study will describe the risk factors and course of treatment of a large cohort of people with PNES. Since PNES are cared for by a variety of different modalities, treatment orientations, and models of care, effectiveness outcomes such as seizure outcomes and utilization of emergency visits for seizures will be assessed. Outcome measurements such as seizure frequency, emergency room visits, hospital admissions, suicide-related behavior, and psychotherapy prior to and after PNES diagnosis will be used to assess the effectiveness of models of care.

Intervention capture helps guide VA pharmacy expansion.

Intervention capture helps guide VA pharmacy expansion.

2402. Daptomycin Pulmonary Eosinophilia: Review of Cases and New Hyperacute Syndromic Presentation

BackgroundDaptomycin pulmonary eosinophilia (DPE) has been described as a rare event. Since the Food and Drug Administration (FDA) first described the syndrome which occurs about 3 weeks after starting the drug, it continues to be a miss diagnosed. Most outpatient antibiotic treatment (OPAT) programs focus on screening for CPK elevations. We describe an unusual increase in DPE at our center including acute reactions on re-exposure to daptomycin.MethodsRetrospective review from local VA pharmacy and OPAT database of adverse drug events (ADE) with daptomycin from 2010 to April 2018. Data evaluated include, age, gender, weight, body mass index (BMI), daptomycin dosing, indication for use, duration of therapy, time to symptom onset, Creatinine clearance, white cell count (WCC), %eosinophilia (%eos), admission to intensive care unit (ICU), and clinical outcomes or interventions.ResultsThere were 363 unique initiations of Daptomycin in the time period. There were 17 DPE (5%) and 3 CPK (0.6%) events in that time period. The medians for all DPE was; Age 68 years (range 55–95), BMI 29 m/kg2 (range 21–49.5), daptomycin dose 500 mg (>7 mg/kg), baseline CrCl 35.5 mL/minute, eosinophilia at onset of DPE 9% (8–44%), and duration of therapy to onset was 21 days (1–33). All recovered on removal of daptomycin, but 5 patients required adjunctive corticosteroid therapy. Four patients had a severe and novel hyperacute DPE within 48 hours of a new initiation of daptomycin therapy. All 4 patients had prior exposure to daptomycin in the last 12 months. They presented with hypoxic respiratory failure, abnormal chest x-rays and/or CT chest scans, with preceding systemic fevers and fatigue after the first dose. All had low grade %eos (3–5%) on prior use, and all recovered rapidly with discontinuation of daptomycin.ConclusionDPE may be underreported and is associated with doses of 500 mg or >7 mg/kg, with CrCl <35 mL/minute and older age. Of concern are the new cases of hyperacute DPE within 48 hours of re-exposure to daptomycin that we have seen, who had prior low-grade eosinophilia. Close monitoring of these factors may be warranted in at risk individuals.Disclosures All authors: No reported disclosures.

Prevalence of Chronic Kidney Disease, Thrombotic Cardiovascular Events, and Use of Oral P2Y12 Inhibitors among Veterans

Background: Contemporary prevalence of chronic kidney disease (CKD) and thrombotic cardiovascular (CV) events remains unclear in Veterans enrolled in the Veterans Affairs Health Care System (VA) care. Although oral P2Y₁₂ inhibitors (P2Y12i) are increasingly being prescribed to this patient population, the overall prescription trend for P2Y12i remains unclear. Methods: Using national VA corporate warehouse data, we used International Classification of Diseases-9 codes to identify Veterans with CKD, dialysis-dependent CKD, and CV events. VA pharmacy data were used to count P2Y12i prescriptions for the federal fiscal years (FY) 2011 through 2015. Results: The period prevalence of Veterans with CKD was 378,233 (6.1%). The point prevalence of CKD increased by 49% from 132,979 (2.30%) in FY11 to 213,444 (3.42%) in FY15. The period prevalence of Veterans with dialysis-dependent CKD was 150,298 (2.4%). In all, 128,703 (56.7%) CV events occurred in Veterans with CKD. Veterans with CKD were given 50.1% of prescriptions for clopidogrel, 49.3% for prasugrel, and 60.4% for ticagrelor. In this patient population, year-to-year increases in P2Y12i prescriptions were observed with a dramatic increase in ticagrelor prescriptions. Conclusion: CKD is common among Veterans and its true prevalence is likely being underestimated. The prevalence of dialysis-dependent CKD is higher among Veterans than the non-Veteran US population. CV events are widely co-prevalent and these patients are commonly prescribed P2Y12i. The recent increase in ticagrelor prescriptions in this patient population and large cost differences between the 3 P2Y12i underline the need for future studies to identify the preferred P2Y12i for these patients.

Patterns of zolpidem use among Iraq and Afghanistan veterans: A retrospective cohort analysis.

BackgroundAlthough concern exists regarding the adverse effects and rate of zolpidem use, especially long-term use, limited information is available concerning patterns of zolpidem use.ObjectiveTo examine the prevalence and correlates of zolpidem exposure in Iraq and Afghanistan Veterans (IAVs).MethodsA retrospective cohort study of zolpidem prescriptions was performed with National Veterans Health Administration (VHA) data. We gathered national VA inpatient, outpatient, and pharmacy data files for IAV’s who received VA care between fiscal years (FY) 2013 and 2014. The VA pharmacy database was used to identify the prevalence of long term (>30 days), high-dose zolpidem exposure (>10mg immediate-release; >12.5mg extended-release) and other medications received in FY14. Baseline characteristics (demographics, diagnoses) were identified in FY13. Bivariate and multivariable analyses were used to examine the demographic, clinical, and medication correlates of zolpidem use.ResultsOf 493,683 IAVs who received VHA care in FY 2013 and 2014, 7.6% (n = 37,422) were prescribed zolpidem in FY 2014. Women had lower odds of high-dose zolpidem exposure than men. The majority (77.3%) of IAVs who received zolpidem prescriptions had long-term use with an average days’ supply of 189.3 days and a minority (0.9%) had high-dose exposure. In multivariable analyses, factors associated with long-term zolpidem exposure included age greater than 29 years old, PTSD, insomnia, Selim Index, physical 2–3 conditions, opioids, antidepressants, benzodiazepines, atypical antipsychotics, and stimulants. High dose exposure was associated with PTSD, depression, substance use disorder, insomnia, benzodiazepines, atypical antipsychotics, and stimulant prescriptions.ConclusionThe current practices of insomnia pharmacotherapy in IAVs fall short of the clinical guidelines and may reflect high-risk zolpidem prescribing practices that put Iraq and Afghanistan Veterans at risk for adverse effects of zolpidem and poor health outcomes.

Blindsided Abroad

Blindsided Abroad Chuck Dean It has been said that an out-of-body experience has little lasting effects, but a near-death experience is capable of changing a person's life in the most dramatic ways. I had such an experience while visiting China in 2006, and can vouch for the truth in that saying. There were no warnings that I was up for a heart attack. Heart disease doesn't generally run in the family and my high blood pressure seemed to be under control by using the medicine issued by the VA pharmacy. However, it did happen and there was nothing I could do but go through the experience. It began on a hot, steamy summer night just three days before I was due to fly back to the U.S.A. My gracious hosts wanted to make sure I had a good send-off with a nice spicy meal, so they took me to one of their favorite street barbecues. Not long after returning to my apartment, however, I was suddenly stricken with what I thought to be acid reflux. It felt different though—much worse—so I downed the pills I usually take to counter the acid. It did not let up though, and by 9:00 pm it had turned into the excruciating chest pains. I agonized for the next several hours but kept taking pills until morning, when it finally subsided. Never having had a heart attack before I had no idea what one felt like, and was not even thinking in that direction. The next day I was pretty wasted from lack of sleep and the trauma my body had endured all night long. We went through the day, and like clockwork as 9:00 pm rolled around, I had the same attack again. Immediately I began downing the acid reflux pills hoping that I could catch it before it got worse. In a moment of calm I sat down and e-mailed my doctor at the VA in Seattle letting her know that I needed to see her as soon as possible upon my return. I told her that something needed to be done about the horrendous acid reflux I was now having. As the evening went on, I experienced the same terrible chest pains for another four to five hours. Sunday was no different, and as if the pain was on a clock, the attack returned at 9:00 pm. [End Page 82] Exhausted, I made it to the airport early Monday morning for my flight home. I few from Nanning to Guangzhou where I was supposed to make a connection on a Delta flight to Los Angeles and then connect from there to Seattle. It was going to be a 20-hour ordeal, but I was happy to be going because I would then go directly to the VA hospital to deal with the intense pain. That didn't happen. After lugging my baggage to the Delta counter, I was informed that the flight to LA had been cancelled and that I needed to stay over to leave the following day. At first I became frustrated but then decided that perhaps it was for the best. A restful day and night in a hotel before the long fight would be good a thing. I checked into a hotel adjacent to the airport, and around 9:00 pm (once again on the clock) I was assaulted again with chest pains. I happened to be on instant messenger with my host in Nanning at the time and all I could do was type "in pain" and then collapsed on the bed. She called the hotel front desk and told them I was in trouble and soon two young hotel employees came to my room, and one, speaking good English, said "sir, we must take you to the hospital." I was checked into Guangzhou People's Municipal Hospital and rushed to the intensive care ward. I was afraid that the language barrier would be an issue, and so far no one in the hospital spoke English—not even the head cardiologist. He came to visit and only looked me over but could not...

Reducing Unnecessary Chronic Use of PPIs in a VA Primary Care Clinic: A QI Project

Introduction: Proton pump inhibitors (PPIs) are a widely used class of medications in the US, with total annual sales exceeding over $10 billion dollars. There has been a recent flurry of studies that associate long term PPI use with increased rate of clostridium difficile colitis, hypomagnesemia, and CKD among others. It is also estimated that up to 60% of patients taking PPIs do not have an appropriate indication for continued use of the medication. Methods: DEFINING THE PROBLEM: In January 2017, we undertook a chart review of 50-patients in the primary care clinic who were on long term PPI therapy (more than one year). This revealed that 80% of these patients did not need to be on a PPI based on societal recommendations. Moreover, VA pharmacy data from November 2016 showed that of the 1003 patients on long term PPI therapy, only 17.6% had a possible indication to be on this medication. AIM OF THE PROJECT: To reduce unnecessary long term PPI therapy by at least 5% in 3 months. PLAN: Educate and encourage Internal Medicine residents to apply an evidence based de-prescribing algorithm to stop unnecessary use of PPIs. INTERVENTIONS: 1) A 15 minute didactic was provided to all residents who had their continuity clinic at the Omaha VA. 2) Residents were provided with an evidence based de-prescribing algorithm to help taper or discontinue PPI use. 3) Residents were given a list of their patients who are on PPIs for more than one year. 4) A new Pharmacy medical therapy management consult was made available to assist with tapering of PPIs. Results: Of the 1003 patients on long term PPI therapy, 168 (16.7%) patients were not on a PPI within 2.5 months of starting the above mentioned interventions. Conclusion: 1) Resident education on: a) Potential side effects of PPIs, b) Appropriate indications of long term PPI use, and c) Application of evidence based de-prescribing algorithm is a very effective tool in reducing unnecessary use of proton pump inhibitors. 2) Educational material including brief lectures, email reminders and/or or handouts should be carried out at least annually for sustained reduction in unnecessary PPI use.

Pharmacy Benefits Management in the Veterans Health Administration Revisited: A Decade of Advancements, 2004-2014.

No outside funding supported this research. This work was supported by VA Pharmacy Benefits Management Services (VA PBM), Hines, Illinois, and VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania. Glassman is co-director of the VA Center for Medication Safety, which is part of the VA PBM. He is also part of the Medical Advisory Panel for the VA PMB. All other authors are employed by the VA PBM. The views expressed in this article are those of the authors, and no official endorsement by the U.S. Department of Veteran Affairs or the U.S. government is intended or should be inferred. Study concept and design were contributed by Valentino, Cunningham, Good, Aspinall, and Sales. Calabrese and Ourth took the lead in data collection, along with Good, Cunningham, Aspinall, Sales, Burk, Moore, Neuhauser, and Golterman. Data interpretation was performed by Burk, Newhauser, and Golterman, along with Glassman, Calabrese, Moore, and Ourth. The manuscript was written by Aspinall and Sales, along with Burk, Newhauser, Golterman, Ourth, and Cunningham. Good, Glassman, and Moore revised the manuscript, along with Calabrese, Valentino, and Aspinall.

Trends in antithrombotic therapy for atrial fibrillation: Data from the Veterans Health Administration Health System

Although controversial, several prior studies have suggested that oral anticoagulants (OACs) are underused in the US atrial fibrillation (AF) population. Appropriate use of OACs is essential because they significantly reduce the risk of stroke in those with AF. In the >2 million Americans with AF, OACs are recommended when the risk of stroke is moderate or high but not when the risk of stroke is low. To quantify trends and guideline adherence, we evaluated OAC use (either warfarin or dabigatran) in a 10-year period in patients with new AF in the Veterans Health Administration. New AF was defined as at least 2 clinical encounters documenting AF within 120 days of each other and no previous AF diagnosis (N = 297,611). Congestive Heart Failure, Hypertension, Age > 75, Diabetes, and Stroke (CHADS2) scores were determined using age and diagnoses of hypertension, diabetes, heart failure, and stroke or transient ischemic attack during the 12 months before AF diagnosis. Receipt of an OAC within 90 days of a new diagnosis of AF was evaluated using VA pharmacy data. Overall, initiation of an OAC fell from 51.3% in 2002 to 43.1% in 2011. For patients with CHADS2 score of 0, 1, 2, 3, 4, and 5-6, the proportions of patients prescribed an OAC showed a relative decrease of 26%, 23%, 14%, 12%, 9%, and 13%, respectively (P < .001). Clopidogrel use was stable at 10% of the AF population. Among US veterans with new AF and additional risk factors for stroke, only about half receive OAC, and the proportion is declining.