Immune checkpoint inhibitor-related adverse events: Real-world experience from a single veterans' affairs medical center.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are antineoplastic agents associated with a multitude of immune-related adverse events (irAEs). Available data from clinical trials include highly selective patient populations which may limit their applicability to real-world clinical practice. METHODS: We present a retrospective cohort study of cancer patients treated with ICI therapy at the Zablocki VA Medical Center between 2014 and 2021. Information on demographics, cancer diagnosis, type of therapy, treatment duration, comorbidities, irAE type, and overall survival were collected. RESULTS: We identified 187 patients who received at least one dose of ICI. About half the patients experienced at least one irAE, the most common categories being fatigue, pulmonary, and endocrine irAEs. Approximately half of the irAEs were diagnosed within the first three months of starting ICI therapy, and 60.38% of those who experienced irAEs discontinued ICI therapy. Patients who experienced endocrine or intestinal irAEs had a significantly longer overall survival. CONCLUSION: Immune-related complications due to ICI therapy are common and can frequently lead to treatment discontinuation in the real-world setting. Endocrine and intestinal irAEs may correlate with improved survival. The ICI-treated patients who received palliative radiation therapy to the bone had less irAEs, possibly due to immunogenic cell death.

Tapered Dose Postoperative Opioid Prescriptions Following Inpatient Total Hip and Knee Arthroplasty: Quality Improvement Study and Retrospective Review.

BACKGROUND: Overprescription of pain medications directly fuels the opioid epidemic. Veterans are profoundly impacted. Tapered dose protocols may reduce excessive prescribing. METHODS: A retrospective study of adult veterans who presented to our institution for primary total knee arthroplasty or total hip arthroplasty (THA) was performed. Postdischarge opioid use was reviewed before and after an opioid taper prescription protocol. The preprotocol and postprotocol groups had 299 and 89 veterans, respectively. Total Morphine Milligram Equivalent (MME) prescribed postdischarge, number of tablets prescribed, number of refills issued, 30-day emergency department visits, and 30-day readmissions were compared. Opioid naïve and chronic opioid users were both included. RESULTS: Preprotocol and postprotocol implementation group, in combination with surgery type (total knee arthroplasty versus THA) and opioid naïve status, predicted MME. On average, the postprotocol group received 224 MME less, THA patients received 177 MME less, and nonopioid naïve patients received 152 MME more. CONCLUSION: The opioid taper protocol led to less opioid administration after discharge. Taper protocols should be considered for postoperative pain management. LEVEL OF EVIDENCE: III, retrospective comparison study.

Predisposing and Precipitating Factors Associated With Postoperative Delirium in Patients Undergoing Cardiac Surgery at a Veterans Affairs Medical Center: A Pilot Retrospective Analysis.

OBJECTIVE: Patients treated at Veterans Affairs (VA) medical centers are in poorer health, experience more medical and psychiatric conditions, and make greater use of medical resources than do patients in the general population. In the present pilot study, the authors examined their recent experience at a VA medical center to determine the incidence and risk factors associated with the development of postoperative delirium in VA patients after cardiac surgery and hypothesized that the risk factors for postoperative delirium after cardiac surgery are different between VA and non-VA patients. DESIGN: Retrospective cohort study. SETTING: Clement J. Zablocki Veterans Affairs Medical Center. PARTICIPANTS: The study comprised 250 consecutive patients undergoing cardiac surgery from July 2014 to March 2016. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographics, coexisting diseases, and medications were obtained from the VA electronic medical record. The European System for Cardiac Operative Evaluation II mortality risk index was calculated for each patient. The type and duration of the procedure and the duration of bypass were recorded. Intraoperative crystalloid, colloid, cell saver, and blood product volumes were compiled. Progress notes and International Classification of Diseases, Tenth Revision, Clinical Modification codes were searched for documentation of postoperative delirium. Thirty-eight patients (15.2%) developed postoperative delirium. Stepwise logistic regression analysis demonstrated that the European System for Cardiac Operative Evaluation II mortality risk index (odds ratio [OR] 1.036, 95% confidence interval [CI] [1.003-1.070]; p = 0.0344), congestive heart failure (OR 2.223 [95% CI 1.046-4.722]; p = 0.0377), pre-existing cognitive impairment (OR 5.147 [95% CI 1.994-13.28]; p = 0.0007), and the presence of a neuropsychiatric disorder (OR 2.015 [95% CI 1.004-4.043]; p = 0.0487) were predisposing factors associated with higher odds of postoperative delirium. The duration of surgery; transfusion of blood products (including packed red blood cells, fresh frozen plasma, and platelets); the durations of mechanical ventilation and conscious sedation (using either propofol or dexmedetomidine); and the length of intensive care unit stay were precipitating factors associated with higher odds of postoperative delirium. CONCLUSIONS: The results demonstrate that congestive heart failure, pre-existing cognitive impairment, and the presence of a neuropsychiatric disorder are predisposing risk factors for postoperative delirium after cardiac surgery in VA patients, whereas the duration of surgery, transfusion of blood products, durations of mechanical ventilation and conscious sedation, and length of intensive care unit stay are precipitating factors for postoperative delirium. These findings in VA patients generally are similar to those observed in the civilian population despite the differences between these cohorts.

How an Audit-and-Feedback-Based Educational Program Contributed to a Reduction in Environmentally Harmful Waste Anesthetic Gases Among Anesthesiology Residents.

Background Waste anesthetic gases (WAGs) contribute to greenhouse gas emissions. US anesthesiology resident education on how to reduce WAG-associated emissions is lacking, so we developed an electronic audit-and-feedback-based program to teach residents to reduce fresh gas flow (FGF) and WAG-associated emissions. Objective To assess the program's effectiveness, we measured individual and combined mean FGF of residents during their first, second, and last weeks of the 4-week rotation; then, we calculated the extrapolated annual emissions based on the combined resident mean FGFs. Resident attitudes toward the program were surveyed. Methods During 4-week rotations at a teaching hospital, anesthesia records were scanned to extract resident-assigned cases, FGF, and volatile anesthetic choice during the 2020-2021 academic year. Forty residents across 3 training years received weekly FGF data and extrapolated WAG-associated emissions data via email. Their own FGF data was compared to the low-flow standard FGF of ≤1 liter per minute (LPM) and to the FGF data of their peer residents on rotation with them. An online survey was sent to residents at the end of the project period. Results Between their first and last weeks on rotation, residents decreased their mean FGF by 22% (1.83 vs 1.42 LPM; STD 0.58 vs 0.44; 95% CI 1.67-2.02 vs 1.29-1.56; P<.0001). Ten of 18 (56%) residents who responded to the survey reported their individual case-based results were most motivating toward practice change. Conclusions An audit-and-feedback-based model for anesthesiology resident education, designed to promote climate-conscious practices with administration of volatile anesthetics, was effective.

Cardiovascular Disease Risk in Calcium Pyrophosphate Deposition Disease: A Nationwide Study of Veterans.

OBJECTIVE: Calcium pyrophosphate deposition (CPPD) disease represents a common crystalline arthritis with a range of manifestations. Our goal was to investigate risks for cardiovascular events in patients with CPPD. METHODS: We performed a retrospective matched cohort analysis in the Veterans Health Administration Corporate Data Warehouse, 2010-2014. CPPD was defined by ≥1 International Classification of Diseases, Ninth Revision codes for chondrocalcinosis or calcium metabolism disorder. CPPD patients were age- and sex-matched to approximately 4 patients without codes for CPPD; we excluded patients with a cardiovascular event during the 365 days prior to the index date. Demographic information, traditional cardiovascular risk factors, medications, and health care utilization were assessed at baseline. The primary outcome was a major adverse cardiovascular event (MACE: myocardial infarction, acute coronary syndrome, coronary revascularization, stroke, or death). Secondary outcomes included individual components of MACE. Cox proportional hazards models estimated fully adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs). RESULTS: We identified 23,124 CPPD patients matched to 86,629 non-CPPD patients with >250,000 person-years of follow-up. The study population was 96% male, mean age was 78 years, and 75% were White. The frequency of traditional cardiovascular risk factors was similar between the 2 cohorts. CPPD was not significantly associated with risk for MACE (HR 0.98 [95% CI 0.94-1.02]) in fully adjusted models, though risks of myocardial infarction, acute coronary syndrome, and stroke were significantly higher in the CPPD cohort compared to the non-CPPD cohort. CONCLUSION: CPPD did not confer an increased risk for MACE, a composite end point including all-cause mortality. Our results propose CPPD as a novel risk factor for MACE components, including myocardial infarction, acute coronary syndrome, and stroke.

Understanding the relationship between patient characteristics and complication in veterans discharged on parenteral antibiotic therapy.

BACKGROUND: Many facilities utilize outpatient parenteral intravenous (IV) antimicrobial therapy (OPAT) to reduce cost, length of stay, and risk of nosocomial infections. OBJECTIVE: The objective of this study was to analyze patient demographics, substance use, mental and physical health diagnoses, and social determinants of health to seek relationships with complications for veterans discharged from the Zablocki Veterans Affairs Medical Center (ZVAMC) on OPAT. METHODS: This study was a retrospective chart review of veterans who completed OPAT between the years of 2013 and 2017 at the ZVAMC in Milwaukee, Wisconsin. Prior to discharge, patients were screened by the OPAT team for eligibility; patients were followed after discharge by pharmacy, home care, and providers. OPAT complication was defined as antibiotic change/dose adjustment, IV catheter complication, or an additional hospital visit secondary to current infection or therapy. RESULTS: 294 veterans' charts were reviewed. Of these patients, 106 (36.05%) had a complication. Tobacco use was the only factor significantly associated with OPAT complication. CONCLUSIONS: Cohabitation, employment status, mental health diagnosis and alcohol use were not associated with OPAT failure; however, tobacco use merits further review for use in OPAT screening protocols.

Implementation of Veterans Affairs Primary Care Antimicrobial Stewardship Interventions For Asymptomatic Bacteriuria And Acute Respiratory Infections.

BACKGROUND: Outpatient antimicrobial prescribing is an important target for antimicrobial stewardship (AMS) interventions to decrease antimicrobial resistance. The objective of this study was to design, implement, and evaluate the impact of AMS interventions focused on asymptomatic bacteriuria (ASB) and acute respiratory infections (ARIs) in the primary care setting. METHODS: This stepped-wedge trial evaluated the impact of multifaceted educational interventions to providers on adult patients presenting to primary care clinics for ARIs and ASB. The primary outcome was percentage of overall antibiotic prescriptions as a composite of prescriptions for ASB, acute bronchitis, upper respiratory infection not otherwise specified, uncomplicated sinusitis, and uncomplicated pharyngitis. Secondary outcomes were the individual components of the primary outcome; a composite safety endpoint of related hospital, emergency department, or primary care visits within 4 weeks; antibiotic selection appropriateness; and patient satisfaction surveys. RESULTS: A total of 887 patients were included (405 preintervention and 482 postintervention). After controlling for type I error using Bonferroni correction, the primary outcome was not significantly different between groups (56% vs 49%). There was a statistically significant decrease in prescriptions for acute bronchitis (20.99% vs 12.66%; P = .0003). Appropriateness of antibiotic prescriptions for uncomplicated sinusitis (odds ratio [OR], 4.96 [95% confidence interval {CI}, 1.79-13.75]; P = .0021) and pharyngitis (OR, 5.36 [95% CI, 1.93-14.90]; P = .0013) was improved in the postintervention vs the preintervention group. The composite safety outcome and patient satisfaction surveys did not differ between groups. CONCLUSIONS: Multifaceted educational interventions targeting providers can improve antibiotic prescribing for indications rarely requiring antimicrobials without increasing re-visits or patient satisfaction surveys.

Wheelchair Athlete Concussion Baseline Data: A Pilot Retrospective Analysis.

OBJECTIVE: The aim of the study was to investigate whether a disabled athlete's underlying disability and concussion history impact the score on baseline testing from a disability modified Graded Symptoms Checklist, Standardized Assessment of Concussion, and Wheelchair Error Scoring System. STUDY DESIGN: This is a retrospective chart review of the 81 veteran wheelchair sports athletes who had baseline concussion evaluations. Demographic data including qualifying disability for the National Veterans Wheelchair Games, scores from the modified Graded Symptoms Checklist, Standardized Assessment of Concussion, and Wheelchair Error Scoring System were analyzed. RESULTS: Forty-three percent of wheelchair athletes reported a history of a concussion. Individuals with a history of a concussion displayed more symptoms on the modified Graded Symptoms Checklist (38.8 vs. 24.71, P = 0.0378) as did those who had a qualifying disability in the brain disorder category (54.87 vs. amputees 24.07 and spinal cord disorders 24.9, P = 0.0015). There was no difference in Standardized Assessment of Concussion examination or Wheelchair Error Scoring System scores based on concussion history or qualifying disability. CONCLUSIONS: Baseline symptom scores from a modified Graded Symptoms Checklist were higher in participants with a history of concussion, independent of their underlying disability, and higher if the athlete's disability was a brain disorder including multiple sclerosis and cerebral vascular accident. Scores on the Standardized Assessment of Concussion examination and Wheelchair Error Scoring System were not affected by the athlete's disability or concussion history. Baseline testing is integral for disabled athletes, especially those with underlying brain disorders and history of concussion.

Does the clock make the poison? Circadian variation in response to pesticides.

BACKGROUND: Circadian clocks govern daily physiological and molecular rhythms, and putative rhythms in expression of xenobiotic metabolizing (XM) genes have been described in both insects and mammals. Such rhythms could have important consequences for outcomes of chemical exposures at different times of day. To determine whether reported XM gene expression rhythms result in functional rhythms, we examined daily profiles of enzyme activity and dose responses to the pesticides propoxur, deltamethrin, fipronil, and malathion. METHODOLOGY/PRINCIPAL FINDINGS: Published microarray expression data were examined for temporal patterns. Male Drosophila were collected for ethoxycoumarin-O-deethylase (ECOD), esterase, glutathione-S-transferase (GST), and, and uridine 5'-diphosphoglucosyltransferase (UGT) enzyme activity assays, or subjected to dose-response tests at four hour intervals throughout the day in both light/dark and constant light conditions. Peak expression of several XM genes cluster in late afternoon. Significant diurnal variation was observed in ECOD and UGT enzyme activity, however, no significant daily variation was observed in esterase or GST activity. Daily profiles of susceptibility to lethality after acute exposure to propoxur and fipronil showed significantly increased resistance in midday, while susceptibility to deltamethrin and malathion varied little. In constant light, which interferes with clock function, the daily variation in susceptibility to propoxur and in ECOD and UGT enzyme activity was depressed. CONCLUSIONS/SIGNIFICANCE: Expression and activities of specific XM enzymes fluctuate during the day, and for specific insecticides, the concentration resulting in 50% mortality varies significantly during the day. Time of day of chemical exposure should be an important consideration in experimental design, use of pesticides, and human risk assessment.