Incidence of transaminitis in adults with cystic fibrosis taking elexacaftor/tezacaftor/ivacaftor.

BACKGROUND: Cystic fibrosis (CF) transmembrane conductance regulator modulators are a cornerstone of CF treatment. However, many patients develop CF liver disease (CFLD) over time, and previous data indicate a risk for transaminase elevation with modulator use. Elexacaftor/tezacaftor/ivacaftor is a commonly prescribed modulator with broad efficacy among CF genomic profiles. Theoretically, elexacaftor/tezacaftor/ivacaftor drug-induced liver injury could exacerbate and further worsen CFLD, but holding modulators can cause a decline in clinical status. OBJECTIVES: This study was designed to determine the real-world incidence of transaminase elevations in adult patients with CF taking elexacaftor/tezacaftor/ivacaftor. METHODS: This exploratory, retrospective descriptive study included all adults with CF-prescribed elexacaftor/tezacaftor/ivacaftor at our institution's outpatient CF clinic. We explored transaminase elevations in 2 separate outcomes: incidence of transaminase elevations of more than 3 times the upper limit of normal (ULN), and transaminase elevations of 25% or more above baseline. RESULTS: 83 patients were prescribed elexacaftor/tezacaftor/ivacaftor. Nine patients (11%) experienced an elevation of more than 3 times ULN and 62 (75%) experienced an elevation of 25% or more above baseline. The median days to transaminase elevation were 108 and 135 days, respectively. Therapy was not discontinued due to transaminase elevations in any of the patients. CONCLUSION: Transaminase elevations among adults taking elexacaftor/tezacaftor/ivacaftor were common but did not result in discontinuation of therapy. Pharmacists should be reassured of the liver safety profile of this important medication for patients with CF.

A Mixed-Methods Program Evaluation of a Self-directed Learning Panel Management Curriculum in an Internal Medicine Residency Clinic.

BACKGROUND: Panel management (PM) curricula in internal medicine (IM) residency programs often assign performance measures which may not address the varied interests or needs of resident-learners. AIM: To evaluate a self-directed learning (SDL)-based PM curriculum. SETTING: University-based primary care practice in Burlington, Vermont. PARTICIPANTS: Thirty-five internal medicine residents participated. PROGRAM DESCRIPTION: Residents completed a PM curriculum that integrated SDL, electronic health record (EHR)-driven performance feedback, mentorship, and autonomy to set learning and patient care goals. PROGRAM EVALUATION: Pre/post-curricular surveys assessed EHR tool acceptability, weekly curricular surveys and post-curricular focus groups assessed resident perceptions and goals, and an interrupted time series analysis of care gap closure rates was used to compare the pre-intervention and intervention periods. Majority of residents (28-32 or 80-91%) completed the surveys and focus groups. Residents found the EHR tools acceptable and valued protected time, mentorship, and autonomy to set goals. A total of 13,313 patient visits were analyzed. There were no significant differences between rates between the pre-intervention period and the first intervention period (p=0.44). DISCUSSION: A longitudinal PM curriculum that incorporated SDL and goal setting with EHR-driven performance feedback was well-received by residents, however did not significantly impact the rate of care gap closure.

Clinical impact of Bachmann's bundle pacing defined by electrocardiographic criteria on atrial arrhythmia outcomes.

AIMS: Evaluate whether Bachmann's bundle pacing (BBp) defined by electrocardiographic (ECG) criteria is associated with less atrial fibrillation/tachycardia (AF/AT) compared with anatomically defined right atrial septal pacing (RASp) and right atrial appendage pacing (RAAp). METHODS AND RESULTS: This is a retrospective study comparing BBp with non-specific RASp and RAAp on new incidence, burden, and recurrence of AF/AT. We included patients who underwent atrial lead placement between 2006 and 2019 and received > 20% atrial pacing. BBp was defined by paced P-wave morphology and fluoroscopic lead position. Compared with RASp (n = 107) and RAAp (n = 108), AF/AT burden was lower in the BBp (n = 134) group by repeated measures ANOVA (P < 0.001). Over 2-year follow-up, AF/AT burden increased in the RASp (P < 0.01) and RAAp (P < 0.01) groups but did not significantly change in the BBp group (P = 0.91). Atrial arrhythmia burden was lower in the BBp group than the RASp and RAAp groups at 12-15, 18-21, and 24-27 months (P < 0.05) after pacemaker placement. Risk of AF/AT recurrence was lower in BBp than RASp (HR 0.43; P < 0.01) and RAAp patients (HR 0.29, P < 0.01). Risk of de novo AF/AT was also lower in BBp than in RASp (OR 0.12; P < 0.01) and RAAp patients (OR 0.20, P < 0.01). CONCLUSION: Bachmann's bundle pacing defined using P-wave criteria was associated with decreased atrial arrhythmia burden, recurrence, and de novo incidence compared with right atrial septal pacing and right atrial appendage pacing.

Rapid infusion of infliximab biosimilars and the incidence and severity of infusion-related reactions in patients with inflammatory bowel disease.

WHAT IS KNOWN AND OBJECTIVE: Infliximab is an anti-tumour necrosis factor agent used in the treatment of inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis. While the use of infliximab is well established in the treatment of IBD, there are now four recently FDA-approved infliximab biosimilars that are increasingly used due to their cost-benefit for patients, institutions and payors. In addition, shortening the length of infliximab infusions from 120 min (standard infusion) to 60 min or less (rapid infusion) has been shown to safely provide further cost-benefit while also improving patient convenience. The safety of rapid infusions has been well-established for the infliximab reference product, however, there are limited data available regarding the safety of rapid infusions for infliximab biosimilars. The purpose of this study was to compare the incidence and severity of infusion reactions among patients with IBD receiving rapid infusion of infliximab reference product compared with infliximab biosimilar. METHODS: This was a retrospective analysis of electronic health record data of patients with a diagnosis of IBD receiving an infliximab reference product or infliximab biosimilar infusion between December 2020 and December 2021. Patient-level variables included demographics, immunomodulator use, IBD-related hospitalization and infliximab trough concentration and antibody levels. Infusion-related variables of interest included total number of infusions, drug, dose, dosing interval, infusion time and use of pre-medications. Infusion-related reactions were defined as safety concerns documented by the administering nurse (anaphylaxis, shortness of breath, hypotension, swelling, rash, pruritus, hives, flushing, chest pain, muscle pain, joint pain, fevers, chills, headache or hypertension) or administration of emergency medications. Fisher's exact test was used to compare reaction rates. RESULTS AND DISCUSSION: A total of 188 patients met inclusion criteria for analysis, and a total of 1124 infusions were administered during the study period. There were no statistically significant differences among any of the pre-specified outcomes. There were no differences in the incidence of infusion reactions among rapid infusion (60 min) infliximab and infliximab biosimilars (p = 0.863). Additionally, there were no differences in the incidence of infusion reactions among standard infusion (120 min) infliximab and infliximab biosimilars (p = 0.993). Finally, there were no differences among the rate of infusion reactions between rapid infusion of infliximab biosimilars and standard infusion of infliximab biosimilars (p = 0.536). Eight patients experienced safety issues, with three patients requiring emergency medications (1.6% of 188 patients). WHAT IS NEW AND CONCLUSIONS: Rapid infusions of infliximab biosimilars were not associated with an increase in the incidence of infusion reactions compared with: rapid infusion of infliximab reference product, standard infusion of infliximab biosimilars, or standard infusion of infliximab reference product. This should reassure clinicians that rapid infusions of infliximab biosimilars are safe in clinical practice.

Integrating DATA 2000 waiver training into undergraduate medical education: The time is now.

Background: Medications for opioid use disorder (MOUD) significantly reduce morbidity and mortality from opioid use disorder (OUD). To prescribe MOUD, physicians must obtain a DEA waiver through requirements outlined in the Drug Addiction Treatment Act of 2000 (DATA 2000). We developed an Addiction Medicine curriculum that features DATA 2000 waiver training at the Robert Larner, MD College of Medicine (LCOM). Methods: All third-year medical students completed a virtual DATA 2000 waiver training at the commencement of clinical clerkships. We conducted a curriculum needs assessment followed by pre- and post-training surveys to evaluate MOUD pharmacology knowledge and best prescribing practices. Results: Of LCOM students surveyed, 77.6% reported interest in being waivered to prescribed MOUD for OUD treatment. Third-year medical students demonstrated increases in both MOUD Pharmacology Knowledge from 64.2% to 84.8% (chi-squared = 40.8; p < .001) and MOUD Best Prescribing Practices from 55.9% to 75.2% (chi-squared = 29.9; p < .001). Discussion: Surveys showed the majority of students felt waiver training was relevant to their future practice. An online DATA 2000 waiver training format effectively improved student knowledge of MOUD. Conclusion: This curriculum exposed medical students to DATA 2000 waiver training, MOUD pharmacology and best practices, and increased the number of future physicians eligible to treat OUD using MOUD.

Causes and outcomes of non-chemotherapy induced neutropenic fever in hospitalized adults: An observational study.

Neutropenic fever in adults undergoing chemotherapy for cancer treatment is a medical emergency and has been the focus of numerous studies. However, there is a paucity of data about non-chemotherapy induced neutropenic fever (non-CINF). We retrospectively reviewed 383 adults with neutropenic fever hospitalized at one academic medical center between October 2015 and September 2020 to characterize the frequency, causes, and outcomes of non-CINF. Twenty-six percent of cases of neutropenic fever were non-chemotherapy induced. Among these, the major causes of neutropenia were hematologic malignancy, infection, and rheumatologic disease, and the major causes of fever were infections. Patients with non-CINF had a higher 30-day mortality than those with chemotherapy induced neutropenic fever (25% vs 13%, P = .01). Non-CINF constituted > 25% of neutropenic fever events in hospitalized adults and was associated with a high mortality rate.

Evaluation of a New Hospital Building's Impact on Clinical Outcomes and Consumer Experience in Medical Inpatients.

Hospitals often seek to improve the effectiveness and experience of care through new building construction. However, the association between the built hospital environment, patient outcomes, and patient experience remains unclear. This retrospective matched cohort study leveraged natural experimental conditions to characterize major clinical outcomes and patient experience in medicine patients admitted to a new hospital building incorporating evidence-based design features compared with controls admitted to legacy buildings. Among patients discharged between June 1, 2019, and March 1, 2020, there were no significant differences in intensive care unit transfer, inpatient mortality, 30-day readmission, 30-day mortality, or length of stay. However, discharge from the new hospital building was associated with a higher percentage of top box scores on the Hospital Consumer Assessment of Healthcare Providers and Systems overall hospital rating item (60% vs 76%, P = 0.02). Further studies are needed to identify specific hospital design features that influence patient experience and clinical outcomes.

Promoting scholarship in improvement science: A model for academic clinical departments.

Introduction: Clinical departments at academic medical centers strive to deliver clinical care, provide education and training, support faculty development, and promote scholarship. These departments have experienced increasing demands to improve the quality, safety, and value of care delivery. However, many academic departments lack a sufficient number of clinical faculty members with expertise in improvement science to lead initiatives, teach, and generate scholarship. In this article, we describe the structure, activities, and early outcomes of a program within an academic department of medicine to promote scholarly improvement work. Methods: The Department of Medicine at the University of Vermont Medical Center launched a Quality Program with three primary goals: (a) improve care delivery, (b) provide education and training, and (c) promote scholarship in improvement science. The program serves as a resource center for students, trainees and faculty, offering education and training, analytic support, consultation in design and methodology, and project management. It strives to integrate education, research, and care delivery to learn, apply evidence and improve health care. Results: Over the first 3 years of full implementation, the Quality Program supported an average of 123 projects annually, including prospective clinical quality improvement initiatives, retrospective assessment of clinical programs and practices, and curriculum development and evaluation. The projects have yielded a total of 127 scholarly products, defined as peer-reviewed publications and abstracts, posters, and oral presentations at local, regional, and national conferences. Conclusions: The Quality Program may serve as a practical model for promoting care delivery improvement, training, and scholarship in improvement science while advancing the goals of a learning health system at the level of an academic clinical department. Dedicated resources within such departments offer the potential to enhance care delivery while promoting academic success for faculty and trainees in improvement science.

Positive and negative psychosocial impact of being diagnosed with cancer as an adolescent or young adult.

BACKGROUND: The objective of this study was to explore the psychosocial impact of cancer on newly diagnosed adolescent and young adult (AYA) cancer patients. METHODS: This was a population-based, multicenter study of 523 newly diagnosed AYA survivors (ages 15-39 years) of germ cell cancer (n = 204), non-Hodgkin lymphoma (n = 131), Hodgkin lymphoma (n = 142), acute lymphocytic leukemia (n = 21), or sarcoma (n = 25) from 7 National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) registries. Age at diagnosis was categorized into 3 groups (ages 15-20 years, 21-29 years, and 30-39 years). RESULTS: Respondents (43% response rate), on average (±standard deviation), were aged 29 = 6.7 years, and most patients (80.1%) were not receiving treatment at the time the completed the survey. With modest differences between the age groups, the most prevalent areas of life impacted in a negative way were financial, body image, control over life, work plans, relationship with spouse/significant other, and plans for having children. Endorsement of positive life impact items also was evident across the 3 age groups, particularly with regard to relationships, future plans/goals, and health competence. CONCLUSIONS: The current results indicated that there will be future need for interventions targeting financial assistance, body image issues, relationships, and helping AYAs to attain their education objectives.

Navigating the Debate on Managing Large (≥4 cm) Thyroid Nodules.

Purpose: Discordant practice guidelines for managing large thyroid nodules may result in unnecessary surgeries and costs. Recent data suggest similar false-negative rates in fine needle aspiration (FNA) biopsies between small (<4 cm) and large (≥4 cm) nodules, indicating that monitoring rather than surgery may be appropriate for large biopsy-negative nodules. We investigated the management of thyroid nodules ≥4 cm to determine the proportion of surgeries not necessary for diagnostic purposes and examined for potential predictors. Methods: This was a retrospective cohort study of patients who received a FNA of nodule(s) ≥4 cm between 11/1/2014 and 10/31/2019 at the University of Vermont Medical Center. A surgery was considered unnecessary if the FNA result was benign in the absence of any of the following: compressive symptoms, family history of thyroid cancer in a first degree relative, history of neck irradiation, toxic nodule or toxic multinodular goiter, or substernal extension. Data were analyzed with Wilcoxon rank sum tests, chi square, or Fisher's exact tests. Results: 177 patients had a ≥4 cm nodule during the timeframe and half (54.2%) had surgery. Patients who underwent surgery were significantly younger (51.5 years vs. 62 years; P < 0.001), more likely to report obstructive symptoms (34.4% vs. 12.1%; P < 0.001) and had a larger nodule size (5.0 cm vs. 4.7 cm; P=0.26). Forty-one patients with benign (Bethesda II) FNA results had surgery, all with negative surgical pathology. Thirteen percentage (23/177) of surgeries were potentially not necessary for diagnostic purposes. Conclusion: Approximately half of our patients with ≥4 cm nodules had surgery, with 13% having surgery not necessary for diagnostic purposes revealing opportunities for improving care and costs.