Comparative effectiveness of omalizumab, mepolizumab, and dupilumab in asthma: A target trial emulation.

BACKGROUND: Multiple mAbs are currently approved for the treatment of asthma. However, there is limited evidence on their comparative effectiveness. OBJECTIVE: Our aim was to compare the effectiveness of omalizumab, mepolizumab, and dupilumab in individuals with moderate-to-severe asthma. METHODS: We emulated a hypothetical randomized trial using electronic health records from a large US-based academic health care system. Participants aged 18 years or older with baseline IgE levels between 30 and 700 IU/mL and peripheral eosinophil counts of at least 150 cells/µL were eligible for study inclusion. The study period extended from March 2016 to August 2021. Outcomes included the incidence of asthma-related exacerbations and change in baseline FEV1 value over 12 months of follow-up. RESULTS: In all, 68 individuals receiving dupilumab, 68 receiving omalizumab, and 65 receiving mepolizumab met the inclusion criteria. Over 12 months of follow-up, 31 exacerbations occurred over 68 person years (0.46 exacerbations per person year) in the dupilumab group, 63 over 68 person years (0.93 per person year) in the omalizumab group, and 86 over 65 person years (1.32 per person year) in the mepolizumab group (adjusted incidence rate ratios: dupilumab vs mepolizumab, 0.28 [95% CI = 0.09-0.84]; dupilumab vs omalizumab, 0.36 [95% CI = 0.12-1.09]; and omalizumab vs mepolizumab, 0.78 [95% CI = 0.32-1.91]). The differences in the change in FEV1 comparing patients who received the different biologics were as follows: 0.11 L (95% CI = -0.003 to 0.222 L) for dupilumab versus mepolizumab, 0.082 L (95% CI -0.040 to 0.204 L) for dupilumab versus omalizumab, and 0.026 L (95% CI -0.083 to 0.140 L) for omalizumab versus mepolizumab. CONCLUSIONS: Among patients with asthma and eosinophil counts of at least 150 cells/µL and IgE levels of 30 to 700 kU/L, dupilumab was associated with greater improvements in exacerbation and FEV1 value than omalizumab and mepolizumab.

Genome-wide association study of asthma, total IgE, and lung function in a cohort of Peruvian children.

BACKGROUND: Genetic ancestry plays a role in asthma health disparities. OBJECTIVE: Our aim was to evaluate the impact of ancestry on and identify genetic variants associated with asthma, total serum IgE level, and lung function. METHODS: A total of 436 Peruvian children (aged 9-19 years) with asthma and 291 without asthma were genotyped by using the Illumina Multi-Ethnic Global Array. Genome-wide proportions of indigenous ancestry populations from continental America (NAT) and European ancestry from the Iberian populations in Spain (IBS) were estimated by using ADMIXTURE. We assessed the relationship between ancestry and the phenotypes and performed a genome-wide association study. RESULTS: The mean ancestry proportions were 84.7% NAT (case patients, 84.2%; controls, 85.4%) and 15.3% IBS (15.8%; 14.6%). With adjustment for asthma, NAT was associated with higher total serum IgE levels (P < .001) and IBS was associated with lower total serum IgE levels (P < .001). NAT was associated with higher FEV1 percent predicted values (P < .001), whereas IBS was associated with lower FEV1 values in the controls but not in the case patients. The HLA-DR/DQ region on chromosome 6 (Chr6) was strongly associated with total serum IgE (rs3135348; P = 3.438 × 10-10) and was independent of an association with the haplotype HLA-DQA1∼HLA-DQB1:04.01∼04.02 (P = 1.55 × 10-05). For lung function, we identified a locus (rs4410198; P = 5.536 × 10-11) mapping to Chr19, near a cluster of zinc finger interacting genes that colocalizes to the long noncoding RNA CTD-2537I9.5. This novel locus was replicated in an independent sample of pediatric case patients with asthma with similar admixture from Brazil (P = .005). CONCLUSION: This study confirms the role of HLA in atopy, and identifies a novel locus mapping to a long noncoding RNA for lung function that may be specific to children with NAT.

Prevalence of anaphylaxis among adults admitted to critical care for severe asthma exacerbation.

BACKGROUND: In asthmatics, making a diagnosis of anaphylaxis could be challenging as respiratory symptoms are a common feature of both conditions. Identifying anaphylaxis is important to providing appropriate care. A prior study showed that anaphylaxis is sometimes misdiagnosed as acute asthma in children. We sought to identify the percentage of adults admitted to the intensive care unit (ICU) with asthma exacerbations who met criteria for anaphylaxis. METHODS: Retrospective chart review of adults admitted with acute asthma to the ICU at Jacobi Medical Center, a Level 1 trauma centre in Bronx, New York. Study period was January 2012 to December 2014. Using the criteria outlined in the World Allergy Organization's Anaphylaxis Guidelines, we identified patients who met criteria for anaphylaxis. RESULTS: 105 patients were identified: 17 were excluded because their main reason(s) for admission was not asthma. 7 (8%) of the 88 cases eligible for the study met diagnostic criteria for anaphylaxis while 3 (3.4%) were highly likely to have had anaphylaxis. The baseline characteristics of the seven patients were similar to that of the overall population studied. They however had shorter onset of symptoms (median (IQR): 3.5 (2-6) vs 24 hours (12-72), p<0.001), were more likely to have been intubated (71%vs31%, p=0.04), received intramuscular epinephrine by the emergency medical services or in the emergency room (86%vs42%, p=0.04) and received antihistamines (28.6%vs1.2%, p=0.02). None of these seven patients died. Only one of the seven patients was prescribed an epinephrine pen injector and referred to an allergist at discharge. CONCLUSION: In this single-centre retrospective review, 3.4% of adults admitted to the ICU for acute severe asthma also met criteria for anaphylaxis.

The development and evaluation of an evidence-based guideline programme to improve care in a paediatric emergency department.

INTRODUCTION: Care guidelines can improve the quality of care by making current evidence available in a concise format. Emergency departments (EDs) are an ideal site for guidelines given the wide variety of presenting conditions and treating providers, and the need for timely decision making. We designed a programme for guideline development and implementation and evaluated its impact in an ED. METHODS: The setting was an urban paediatric ED with an annual volume of 60 000. Common and/or high-risk conditions were identified for guideline development. Following implementation of the guidelines, their impact on effectiveness of care, patient outcomes, efficiency and equitability of care was assessed using a web-based provider survey and performance on identified metrics. Variation in clinical care between providers was assessed using funnel plots. RESULTS: Eleven (11) guidelines were developed and implemented. 3 years after the initiation of the programme, self-reported adherence to recommendations was high (95% for physicians and 89% for nurses). 97% of physicians and 92% of nurses stated that the programme improved the quality of care in the ED. For some guidelines, provider-to-provider care practice variation was reduced significantly. We found reduced disparity in imaging when assessing one guideline. There were also reductions in utilisation of diagnostic tests or therapies. As a balancing measure, the percentage of patients with any of the guideline conditions who returned to the ED within 72 h of discharge did not change from before to after guideline initiation. Overall, 80% of physician and 56% of nurse respondents rated the guideline programme at the highest value. CONCLUSIONS: A programme for guideline development and implementation helped to improve efficiency, and standardise and eliminate disparities in emergency care without jeopardising patient outcomes.

Lower Use of Biologics for the Treatment of Asthma in Publicly Insured Individuals.

BACKGROUND: Despite bearing a disproportionate burden of poorly controlled asthma, publicly insured individuals are less likely to receive biologics. OBJECTIVE: To assess biologic use by payer among individuals with asthma. METHODS: We used IQVIA's National Disease and Therapeutic Index, a nationally representative, all-payer audit of ambulatory care in the United States, to describe the patterns of use by payer. RESULTS: Asthma treatment visits in which a biologic product was reported increased from approximately 0.1% of asthma-related visits in 2003 to 1% in 2015 and doubled to 2% by 2019. Omalizumab use initially increased from 2003 to 2006 and plateaued till 2015 when its use declined modestly, coinciding with the release of additional biologic products. In 2019, omalizumab accounted for 37% of biologic treatment visits, mepolizumab 21%, benralizumab 27%, dupilumab 15%, and reslizumab <1%. Biologic treatment visits were higher for privately insured individuals (28.3 per 1000 visits) compared with publicly insured individuals (16.3 per 1000 visits). This difference persisted after accounting for age, sex, and race using nationally representative estimates. White patients accounted for a disproportionate amount of biologic treatment visits among the publicly insured (80%) despite accounting for only 60% of publicly insured asthma treatment visits. No biologic treatment visits were observed for individuals who were uninsured. Half of dupilumab visits were for publicly insured patients, compared with 22% of mepolizumab/benralizumab and 27% of omalizumab visits. CONCLUSION: Biologics were uncommonly used among patients with asthma, and the basis for disproportionately lower use of biologics among the publicly insured, where the burden of uncontrolled asthma is greatest, merits further investigation.

Implementing an Electronic Medical Record-Based Reminder for Cardiovascular Risk Screening in Rheumatoid Arthritis.

OBJECTIVE: Although cardiovascular disease (CVD) is the leading cause of death among individuals with rheumatoid arthritis (RA), CVD risks are not being assessed frequently and systematically in RA. We implemented an electronic medical record (EMR)-based reminder in a tertiary care center and assessed the effects of this intervention on CVD risk screening by rheumatologists and primary care providers. METHODS: The EMR reminder was implemented in December 2013 and included the most recent value and target ranges for body mass index, blood pressure (BP), and lipid profiles. It was displayed for every rheumatology and primary care visit for all patients with the International Classification of Diseases, Ninth Revision code for RA (714.0). Lipid screening rates, as well as changes in BP and obesity rates were compared pre- and postimplementation. Factors associated with lipid screening postimplementation were assessed using multivariate logistic regression. RESULTS: A total of 138 and 112 RA patients were seen in the outpatient clinics pre- and postimplementation, respectively. The demographic characteristics were similar in the pre- and postimplementation groups. Lipid screening rates were 50% preimplementation and 46% postimplementation (P = 0.58). There were no significant improvements in BP or obesity rates postimplementation. Factors associated with the higher odds of lipid screening included older age and history of diabetes mellitus. CONCLUSION: Implementing an EMR reminder did not improve CVD risk screening among RA patients. Future research is needed to identify and address barriers to CVD screening, and to educate patients and providers about RA-related risks.

Impact of a bronchiolitis guideline on ED resource use and cost: a segmented time-series analysis.

OBJECTIVE: Bronchiolitis is a major cause of infant morbidity and contributes to millions of dollars in health care costs. Care guidelines may cut costs by reducing unnecessary resource utilization. Through the implementation of a guideline, we sought to reduce unnecessary resource utilization and improve the value of care provided to infants with bronchiolitis in a pediatric emergency department (ED). METHODS: We conducted an interrupted time series that examined ED visits of 2929 patients with bronchiolitis, aged 1 to 12 months old, seen between November 2007 and April 2013. Outcomes were proportion having a chest radiograph (CXR), respiratory syncytial virus (RSV) testing, albuterol or antibiotic administration, and the total cost of care. Balancing measures included admission rate, returns to the ED resulting in admission within 72 hours of discharge, and ED length of stay (LOS). RESULTS: There were no significant preexisting trends in the outcomes. After guideline implementation, there was an absolute reduction of 23% in CXR (95% confidence interval [CI]: 11% to 34%), 11% in RSV testing (95% CI: 6% to 17%), 7% in albuterol use (95% CI: 0.2% to 13%), and 41 minutes in ED LOS (95% CI: 16 to 65 minutes). Mean cost per patient was reduced by $197 (95% CI: $136 to $259). Total cost savings was $196,409 (95% CI: $135,592 to $258,223) over the 2 bronchiolitis seasons after guideline implementation. There were no significant differences in antibiotic use, admission rates, or returns resulting in admission within 72 hours of discharge. CONCLUSIONS: A bronchiolitis guideline was associated with reductions in CXR, RSV testing, albuterol use, ED LOS, and total costs in a pediatric ED.

Prevalence and predictors of return visits to pediatric emergency departments.

OBJECTIVE: To determine the rate of return visits to pediatric emergency departments (EDs) and identify patient- and visit-level factors associated with return visits and hospitalization upon return. DESIGN AND SETTING: Retrospective cohort study of visits to 23 pediatric EDs in 2012 using data from the Pediatric Health Information System. PARTICIPANTS: Patients <18 years old discharged following an ED visit. MEASURES: The primary outcomes were the rate of return visits within 72 hours of discharge from the ED and of return visits within 72 hours resulting in hospitalization. RESULTS: 1,415,721 of the 1,610,201 ED visits to study hospitals resulted in discharge. Of the discharges, 47,294 patients (3.3%) had a return visit. Of these revisits, 9295 (19.7%) resulted in hospitalization. In multivariate analyses, the odds of having a revisit were higher for patients with a chronic condition (odds ratio [OR]: 1.91, 95% confidence interval [CI]: 1.86-1.96), higher severity scores (OR: 1.42, 95% CI: 1.40-1.45), and age <1 year (OR: 1.32, 95% CI: 1.22-1.42). The odds of hospitalization on return were higher for patients with higher severity (OR: 3.42, 95% CI: 3.23-3.62), chronic conditions (OR: 2.92, 95% CI: 2.75-3.10), age <1 year (1.7-2.5 times the odds of other age groups), overnight arrival (OR: 1.84, 95% CI: 1.71-1.97), and private insurance (OR: 1.47, 95% CI: 1.39-1.56). Sickle cell disease and cancer patients had the highest rates of return at 10.7% and 7.3%, respectively. CONCLUSIONS: Multiple patient- and visit-level factors are associated with revisits. These factors may provide insight in how to optimize care and decrease avoidable ED utilization.

Surgical Care in the Developing World-Strategies and Framework for Improvement.

The purpose of this study was to identify the various problems with surgical care in the developing world and enumerate identified strategies or propose solutions. We also sought to rank these strategies in order of potential impact. The MEDLINE database was sought. Studies published in English, reporting currently employed solutions to identified barriers or problems to surgical care in developing countries or potential solution(s) and published between 2000 and 2012 were eligible for inclusion. 2156 articles were identified for possible inclusion. MeSH terms include surgery, general surgery, developing countries, health services accessibility and quality improvement. Forty-nine full articles with a primary focus on the solutions to the challenges to surgical care in the developing world were included in the final review. Many articles identified problems with infrastructure, workforce shortage, inadequate or inappropriate policies, and poor financing as major problems with healthcare in the developing world. Solutions addressing these problems are multifactorial and would require active participation of local authorities and collaboration with providers from the developed world. The burden of surgical care is increasing. There is poor access to surgical services in the developing world. If and when surgical care is received, the quality could be less than the standard in developed nations. Solutions exist to tackle these problems but require a multidimensional approach to be successful.