Introduction of a penicillin allergy de-labelling program with direct oral challenge and its effects on utilization of beta-lactam antimicrobials: a multicenter retrospective parallel cohort study.

BACKGROUND: Self-reported penicillin allergy labels are common and often inaccurate after assessment. These labels can lead to reduced use of first-line beta-lactam antibiotics and worse outcomes. We measured the impact of a previously performed inpatient proactive systematic penicillin allergy de-labelling program on subsequent antibiotic use. This prior program included assessment, risk-stratification, and low risk direct oral amoxicillin challenge. METHODS: We performed a retrospective comparison of parallel cohorts from two separate tertiary care hospital campuses in Ottawa, Canada across two penicillin de-labelling intervention periods across April 15th to April 30th, 2021, and February 15th to March 8th, 2022. Outcomes, including penicillin allergy labelling and antibiotic use, were collected for the index admission and the subsequent 6-month period. Descriptive statistics and multivariate regression analyses were performed. RESULTS: A total of 368 patients with penicillin allergy label were included across two campuses and study periods. 24 (13.8%) patients in the intervention groups had sustained penicillin allergy label removal at 30 days from admission vs. 3 (1.5%) in the non-intervention group (p < 0.001). In the 6-months following admission, beta-lactams were prescribed more frequently in the intervention groups vs. the non-intervention groups for all patients (28 [16.1%] vs.15 [7.7%], p = 0.04) and were prescribed more frequently amongst those who received at least one antibiotic (28/46 [60.9%] vs.15/40 [37.5%], p = 0.097). In a multivariate regression analysis, the intervention groups were found to be associated with an increased odds of beta-lactam prescribing in all patients (OR 2.49, 95%CI 1.29-5.02) and in those prescribed at least one antibiotic (OR 2.44, 95%CI 1.00-6.15). No drug-related adverse events were reported. CONCLUSIONS: Proactive penicillin allergy de-labelling for inpatients was associated with a reduction in penicillin allergy labels and increased utilization of beta-lactams in the subsequent 6-months.

Resource utilization and cost assessment of a proactive penicillin allergy de-labeling program for low-risk inpatients.

BACKGROUND: Resource utilization and costs can impede proactive assessment and de-labeling of penicillin allergy among inpatients. METHODS: Our pilot intervention was a proactive penicillin allergy de-labeling program for new inpatients with penicillin allergy. Patients deemed appropriate for a challenge with a low-risk penicillin allergy history were administered 250 mg amoxicillin and monitored for 1 h. We performed an explorative economic evaluation using various healthcare professional wages. RESULTS: Over two separate 2-week periods between April 2021 and March 2022, we screened 126 new inpatients with a penicillin allergy. After exclusions, 55 were appropriate for formal assessment. 19 completed the oral challenge, and 12 were directly de-labeled, resulting in a number needed to screen of 4 and a number needed to assess of 1.8 to effectively de-label one patient. The assessor's median time in the hospital per day de-labeling was 4h08 with a range of (0h05, 6h45). A single-site annual implementation would result in 715 penicillin allergy assessments with 403 patients de-labeled assuming 20,234 annual weekday admissions and an 8.9% penicillin allergy rate. Depending on the assessor used, the annual cost of administration would be between $21,476 ($53.29 per effectively de-labeled patient) for a pharmacy technician and $61,121 ($151.67 per effectively de-labeled patient) for a Nurse Practitioner or Physician Assistant. CONCLUSION: A proactive approach, including a direct oral challenge for low-risk in-patients with penicillin allergy, appears safe and feasible. Similar programs could be implemented at other institutions across Canada to increase access to allergy assessment.

Concurrence of familial Mediterranean fever and Behçet's disease: a case report and review of the literature.

BACKGROUND: Familial Mediterranean fever and Behçet's disease are distinct disorders that are prevalent in the Mediterranean and Middle Eastern populations. They are characterized by unprovoked inflammatory episodes caused by overexpression of proinflammatory cytokines. Although reported previously, the overlapping presentation of familial Mediterranean fever and Behçet's disease remains uncommon. CASE PRESENTATION: A 46-year-old Lebanese-Canadian man who presented with recurrent oral and genital ulcers, polyarticular synovitis, ocular swelling, recurrent infections, and fevers was later found to have heterozygous mutations of pathogenic MEFV c.2080A > G (p. Met 694Val) and c.2082G > A (p.Met694IIe) genes indicating familial Mediterranean fever. He was treated with prednisone, colchicine, and azathioprine, with inadequate symptoms control. Treatment was complicated by recurrent infections. CONCLUSIONS: Our case contributes to the growing literature demonstrating the presentation of predominantly Behçet's disease-like features in the setting of diagnosis of familial Mediterranean fever. These findings emphasize that clinicians should be aware that patients with familial Mediterranean fever may present with Behçet's disease-like clinical manifestations.

Inflammatory biomarkers as independent prognosticators of 28-day mortality for COVID-19 patients admitted to general medicine or ICU wards: a retrospective cohort study.

Inflammatory biomarkers may be associated with disease severity and increased mortality in COVID-19 patients but have not been studied in North American populations. We sought to determine whether a set of commonly ordered inflammatory biomarkers can predict 28-day mortality. We analyzed a multi-centered (four) COVID-19 registry cohort from March 4th to December 7th, 2020. This cohort included COVID-19-positive patients admitted to medical wards or intensive care units. Patients presenting to the emergency department for COVID-19 symptoms and then subsequently discharged were also included. We performed Cox-regression analysis to measure whether commonly used biomarkers were associated with an increased 28-day mortality. Of 336 COVID-19-positive patients, 267 required hospital admission, and 69 were seen in the emergency room and discharged. The median age was 63 years (IQR 80-50) and the female-to-male ratio was 49:51. Derivation of internally validated cut-offs suggested that C-reactive protein ≥ 78.4 mg/L, neutrophil-to-lymphocyte ratio ≥ 6.1, lymphocyte-to-white blood cell ratio < 0.127, and a modified Glasgow prognostic score equal to 2 vs. 1 or 0 were associated with the highest increased risk of 28-day mortality. We provide early estimates of cut-off values for inflammatory biomarkers and indices measured at the time of admission that may be useful to clinicians for predicting 28-day mortality in North American COVID-19 patients.

Is There A Causal Relationship between Childhood Obesity and Acute Lymphoblastic Leukemia? A Review.

Childhood obesity is a growing epidemic with numerous global health implications. Over the past few years, novel insights have emerged about the contribution of adult obesity to cancer risk, but the evidence base is far more limited in children. While pediatric patients with acute lymphoblastic leukemia (ALL) are at risk of obesity, it is unclear if there are potential causal mechanisms by which obesity leads to ALL development. This review explores the endocrine, metabolic and immune dysregulation triggered by obesity and its potential role in pediatric ALL's genesis. We describe possible mechanisms, including adipose tissue attraction and protection of lymphoblasts, and their impact on ALL chemotherapies' pharmacokinetics. We also explore the potential contribution of cytokines, growth factors, natural killer cells and adipose stem cells to ALL initiation and propagation. While there are no current definite causal links between obesity and ALL, critical questions persist as to whether the adipose tissue microenvironment and endocrine actions can play a causal role in childhood ALL, and there is a need for more research to address these questions.

Reducing Door-to-Needle Time for Tissue Plasminogen Activator Administration in a Community Hospital: An Operations Study.

BACKGROUND AND OBJECTIVES: The benefit of tissue plasminogen activator (tPA) in acute ischemic stroke is time dependent. A 15-minute decrease in door-to-needle (DTN) time has been associated with increased odds of ambulating independently, faster discharge, and decreased odds of death. We investigated common causes of delay in DTN times in a community hospital setting in order to identify areas for improvement. METHODS: A retrospective medical record review was conducted at a 574-bed community hospital. This included 100 patients who received tPA from 2016 to 2019. Time segments were classified a priori to reflect key work elements from the time between hospital arrival to tPA and recorded for each chart. Linear regression models were used to identify work elements associated with increased DTN time. RESULTS: Median DTN time was 54:29 minutes. Linear regression analyses determined that differences in NIHSS score (P = .030), triage to computed tomography (CT) start (P = .017), triage to stroke physician page (P = .016), and CT report to tPA administration (P < .001) were associated with increased DTN time. CT report to tPA administration was most strongly associated with a Pearson coefficient of 0.868 (P < .001) with increased DTN time. CONCLUSIONS: The DTN time at our institution was above the recommended target. Our findings suggest that reducing the CT report time interval may decrease DTN time.