A nurse-driven penicillin allergy risk score in the preoperative setting was associated with increased cefazolin use perioperatively.

STUDY OBJECTIVE: To characterize and assess the effects of a preoperative, nurse-driven penicillin allergy risk stratification tool on rates of perioperative cefazolin and second-line antibiotic use. DESIGN: Quasi-experimental quality improvement study of penicillin-allergic surgical patients undergoing procedures for which cefazolin is indicated. SETTING: Outpatient Perioperative Care Clinic (PCC) for preoperative surgical patients at a tertiary care center. PATIENTS: 670 and 1371 adult penicillin-allergic PCC attendants and non-attendants, respectively. INTERVENTION: A paper penicillin allergy risk stratification questionnaire was administered during the PCC visit. Nurses were educated on its use. MEASUREMENTS: Antibiotic (cefazolin, clindamycin, vancomycin) use rates in the 24 months before and 17 months after intervention implementation in November 2020 (November 2018 - April 2022) were assessed in penicillin-allergic PCC attendants with statistical process control charts. Multivariable logistic regression assessed antibiotic use rates pre- and post-intervention adjusting for age, sex, surgical specialty and penicillin allergy history severity. Similar analyses were done in penicillin-allergic PCC non-attendants. MAIN RESULTS: Of 670 penicillin-allergic PCC attendants, 451 (median [IQR] age, 66 (Sousa-Pinto et al., 2021 [14])) were analyzed pre-intervention and 219 (median [IQR] age, 66 (Mine et al., 1970 [13])) post-intervention. One month after implementation, process measures demonstrated an upward shift in cefazolin use for PCC attendants versus no shift or other special cause variation for PCC non-attendants. There were increased odds of cefazolin use (aOR 1.67, 95% CI [1.09-2.57], P = 0.019), decreased odds of clindamycin use (aOR 0.61, 95% CI [0.42-0.89], P = 0.010) and decreased odds of vancomycin use (aOR 0.56, 95% CI [0.35-0.88], P = 0.013) in PCC attendants post-intervention. This effect did not occur in PCC non-attendants. There was no increase in perioperative anaphylaxis post-intervention. CONCLUSIONS: A simple penicillin allergy risk stratification tool implemented in the preoperative setting was associated with increased use of cefazolin and decreased rates of second-line agents post implementation.

Comparing body mass index and obesity-related comorbidities as predictors in hospitalized COVID-19 patients.

The association between body mass index (BMI) and poor COVID-19 outcomes in patients has been demonstrated across numerous studies. However, obesity-related comorbidities have also been shown to be associated with poor outcomes. The purpose of this study was to determine whether BMI or obesity-associated comorbidities contribute to elevated COVID-19 severity in non-elderly, hospitalized patients with elevated BMI (≥25 kg/m2 ). This was a single-center, retrospective cohort study of 526 hospitalized, non-elderly adult (aged 18-64) COVID-19 patients with BMI ≥25 kg/m2 in suburban New York from March 6 to May 11, 2020. The Edmonton Obesity Staging System (EOSS) was used to quantify the severity of obesity-related comorbidities. EOSS was compared with BMI in multivariable regression analyses to predict COVID-19 outcomes. We found that higher EOSS scores were associated with poor outcomes after demographic adjustment, unlike BMI. Specifically, patients with increased EOSS scores had increased odds of acute kidney injury (adjusted odds ratio [aOR] = 6.40; 95% CI 3.71-11.05), intensive care unit admission (aOR = 10.71; 95% CI 3.23-35.51), mechanical ventilation (aOR = 3.10; 95% CI 2.01-4.78) and mortality (aOR = 5.05; 95% CI 1.83-13.90). Obesity-related comorbidity burden as determined by EOSS was a better predictor of poor COVID-19 outcomes relative to BMI, suggesting that comorbidity burden may be driving risk in those hospitalized with elevated BMI.

Concurrent asthma and chronic obstructive pulmonary disease in adult ED patients: A national perspective.

OBJECTIVES: Emergency department (ED) visits for Asthma and Chronic Obstructive Pulmonary Disease (COPD) are common. The designation of Asthma-COPD overlap (ACO) has been used to describe patients with features of both diseases. Studies show that ACO patients may be at increased risk of poor outcomes relative to patients with either disease alone. We sought to characterize ED visits and ED-related outcomes of patients with ACO compared to patients with Asthma or COPD alone. METHODS: We conducted a secondary analysis of the National Hospital Ambulatory Medical Care Survey (NHAMCS, 2005-2018) characterizing ED visits in patients ≥35 years of age with Asthma Only, COPD Only or ACO. We performed univariable and multivariable analyses adjusting for demographics to assess relevant ED outcome variables. RESULTS: From 2005 to 2018, there were an estimated 8.15, 17.78 and 0.56 million ED visits for Asthma Only, COPD Only and ACO, respectively. ACO patients were younger than COPD Only patients (mean age 50.18 versus 61.79; p < 0.001). ACO patients differed in terms of sex, race and ethnicity from patients with either disease alone. When triaged, Asthma Only (adjusted odds ratio (aOR) = 11.45; 95% confidence interval (CI), 1.20-109.38) patients were more likely to require immediate care than ACO patients. Although admission rates were comparable between groups, ACO patients had a decreased mean length of ED visit compared to both Asthma Only (p < 0.001) and COPD Only (p < 0.05) patients. COPD Only patients were less likely than ACO patients to be seen in the ED in the last 72 h (aOR = 0.22; 95% CI, 0.056-0.89), receive nebulizer therapy (aOR = 0.55; 95% CI, 0.31-0.97), bronchodilators (aOR = 0.24; 95% CI, 0.12-0.48) and systemic corticosteroids (aOR = 0.18; 95% CI, 0.091-0.35). Asthma Only patients were less likely than ACO patients to undergo any imaging (aOR = 0.55; 95% CI, 0.31-0.96) and receive antibiotics (aOR = 0.46; 95% CI, 0.23-0.93). CONCLUSIONS: ACO patients appear to differ demographically from patients with either disease alone in the ED. After adjustment for these demographic differences, ACO patients appear to differ with respect to several ED variables, notably respiratory therapies; however, clinical outcomes including admission and mortality rates appear to be comparable between groups.

Targeting the IL-5 pathway in eosinophilic asthma: a comparison of mepolizumab to benralizumab in the reduction of peripheral eosinophil counts.

BACKGROUND: Mepolizumab and benralizumab are biologics approved for severe eosinophilic asthma. Mepolizumab is an anti-interlukin-5 (IL-5) antibody while benralizumab is an anti-interleukin-5 receptor alpha (IL-5Rα) antibody targeting the IL-5 receptor on eosinophils. Both therapies reduce oral corticosteroid requirements and asthma exacerbations. However, no head-to-head studies have been published. The aim of the present study was to compare the efficacy of peripheral eosinophil reduction of mepolizumab and benralizumab. METHODS: A retrospective chart review was conducted on patients with severe eosinophilic asthma who were approved for either IL-5 agent. Patients with noted non-adherence or those who were on fluctuating doses of corticosteroids for non-asthma related illnesses were excluded. The last detectable eosinophil count for each patient prior to start of therapy was compared to the highest eosinophil count noted after therapy start with at least 30 days of adherence. RESULTS: Thirty-six patients taking mepolizumab and 19 patients taking benralizumab met the inclusion criteria and had both pre-treatment and post-treatment eosinophil counts. Baseline characteristics were not statistically different between those on mepolizumab and benralizumab therapy. The mean pre-therapy serum eosinophil count did not statistically differ between patients on mepolizumab (597.2 cells/µL) compared to benralizumab (521.6 cells/µL), p = 0.3769. While both therapies resulted in a significant decrease in eosinophil count (p < 0.0001); the mean decrease did not statistically differ between patients taking mepolizumab compared to those on benralizumab, p = 0.9079. Nonetheless, 100% of patients receiving benralizumab had undetectable eosinophil counts post-therapy compared to 31% of patients receiving mepolizumab (p < 0.0001). CONCLUSION: Both mepolizumab and benralizumab are potent targets of the IL-5 pathway with the ability to significantly reduce peripheral eosinophil counts. While there is there is no statistical difference in the magnitude of eosinophil reduction offered by each agent, benralizumab is able to decrease peripheral eosinophil counts to 0 cells/µL in more patients than mepolizumab.

Eligibility of monoclonal antibody-based therapy for patients with severe asthma: a Canadian cross-sectional perspective.

BACKGROUND: Based on immunologic phenotypes underlying asthma, use of monoclonal antibody based therapies is becoming the new standard of care for severe, corticosteroid refractory clinical symptoms. Patients may qualify for one or more of these targeted treatments, based on clinical characteristics and approved indications. However, the statistics are not well characterized, particularly in the Canadian population. METHODS: The objective of this observational study was to identify and describe the proportion of patients with severe asthma who were eligible for targeting IgE, IL-5, or both pathways of immunomodulation. We reviewed a cross-sectional cohort of patients in a Canadian Allergy and Immunology referral practice. We also compared demographic and clinical characteristics of each group. RESULTS: Of the 128 patients with severe asthma, 84 (66%) were eligible for omalizumab, 100 (78%) for mepolizumab, 52 (41%) for reslizumab, and 68 (53%) for benralizumab. Overlap in treatment eligibility varied; 68 (53%) patients were eligible for both omalizumab and mepolizumab, 47 (37%) were eligible for omalizumab and benralizumab, and 37 (29%) were eligible for all four medications. Patient demographics and clinical characteristics were similar, and levels of serum biomarkers varied based on locally approved prescribing criteria. CONCLUSION: In this severe asthma population from a Canadian Allergist's practice, one-third of individuals qualified for all currently available biologics. 41-78% were eligible for at least one mAb. Patients were most likely to be eligible for mepolizumab. Objective assessments to determine asthma phenotype, along with further characterization of safety profiles will lead to further advances in asthma management.

High rate of house dust mite sensitization in a shrimp allergic southern Ontario population.

BACKGROUND: Shrimp and house dust mite (HDM) allergies are common in Canadians. Often, both of these allergies occur in the same patient. This may be due to homology of tropomyosin or other potentially shared proteins. The aim of our study was to assess the frequency of house dust mite sensitization in a shrimp allergic Canadian population. METHODS: We undertook a retrospective chart review of shrimp allergic patients at an outpatient allergy clinic in Kitchener, Ontario, Canada. Our primary endpoint was to assess for presence of HDM sensitization in this population. Patients were categorized into approximate quartiles. We assessed the severity of the shrimp reactions, correlated shrimp skin test size to HDM skin test size, and measured the proportion of patients with atopic symptoms. RESULTS: We identified 95 shrimp allergic patients who were tested for house dust mite. 86 (90.5%) of these patients had a positive skin test to HDM. Patients with a shrimp skin test ≥5 mm were 5.31 times (95% CI, 1.55-18.14; p = 0.008) more likely to exhibit a dust mite skin test ≥5 mm than patients with a shrimp skin test <5 mm. The odds of a patient with a shrimp skin test between 10 and 18 mm having a larger HDM skin test were 3.93 times (95% CI 1.03-14.98, p = 0.045) the odds for a patient with a shrimp skin test size between 3 and 4 mm. We did not find a correlation between shrimp skin test size and shrimp reaction symptom grade (p = 0.301). CONCLUSION: In our Canadian patients, we found a large majority of shrimp allergic patients to be sensitized to HDM. We found that patients with a large skin test to shrimp were more likely to have a large skin test to HDM compared to those patients with a small skin test to shrimp. We did not find a correlation between shrimp skin test size and shrimp reaction symptom severity. Most of these patients had symptoms of rhinitis and/or asthma that may have been caused by house dust mite allergy.

Maternal High-Fat Diet-Induced Loss of Fetal Oocytes Is Associated with Compromised Follicle Growth in Adult Rat Offspring.

Maternal obesity predisposes offspring to metabolic and reproductive dysfunction. We have shown previously that female rat offspring born to mothers fed a high-fat (HF) diet throughout pregnancy and lactation enter puberty early and display aberrant reproductive cyclicity. The mechanisms driving this reproductive phenotype are currently unknown thus we investigated whether changes in ovarian function were involved. Wistar rats were mated and randomized to: dams fed a control diet (CON) or dams fed a HF diet from conception until the end of lactation (HF). Ovaries were collected from fetuses at Embryonic Day (E) 20, and neonatal ovaries at Day 4 (P4), prepubertal ovaries at P27 and adult ovaries at P120. In a subset of offspring, the effects of a HF diet fed postweaning were evaluated. The present study shows that fetuses of mothers fed a HF diet had significantly fewer oocytes at E20, and in neonates, have reduced AMH signaling that may facilitate an increased number of assembled primordial follicles. Both prepubertally and in adulthood, ovaries show increased follicular atresia. As adults, offspring have reduced FSH responsiveness, low expression levels of estrogen receptor alpha (Eralpha), the oocyte-secreted factor, Gdf9, oocyte-specific RNA binding protein, Dazl, and high expression levels of the granulosa-cell derived factor, AMH, in antral follicles. Together, these data suggest that ovarian compromise in offspring born to HF-fed mothers may arise from changes already observable in the fetus and neonate and in the long term, associated with increased follicular atresia through adulthood.