Development of a core outcome set for therapeutic studies in eosinophilic esophagitis (COREOS).

BACKGROUND: End points used to determine treatment efficacy in eosinophilic esophagitis (EoE) have evolved over time. With multiple novel therapies in development for EoE, harmonization of outcomes measures will facilitate evidence synthesis and appraisal when comparing different treatments. OBJECTIVE: We sought to develop a core outcome set (COS) for controlled and observational studies of pharmacologic and diet interventions in adult and pediatric patients with EoE. METHODS: Candidate outcomes were generated from systematic literature reviews and patient engagement interviews and surveys. Consensus was established using an iterative Delphi process, with items voted on using a 9-point Likert scale and with feedback from other participants to allow score refinement. Consensus meetings were held to ratify the outcome domains of importance and the core outcome measures. Stakeholders were recruited internationally and included adult and pediatric gastroenterologists, allergists, dieticians, pathologists, psychologists, researchers, and methodologists. RESULTS: The COS consists of 4 outcome domains for controlled and observational studies: histopathology, endoscopy, patient-reported symptoms, and EoE-specific quality of life. A total of 69 stakeholders (response rate 95.8%) prioritized 42 outcomes in a 2-round Delphi process, and the final ratification meeting generated consensus on 33 outcome measures. These included measurement of the peak eosinophil count, Eosinophilic Esophagitis Histology Scoring System, Eosinophilic Esophagitis Endoscopic Reference Score, and patient-reported measures of dysphagia and quality of life. CONCLUSIONS: This interdisciplinary collaboration involving global stakeholders has produced a COS that can be applied to adult and pediatric studies of pharmacologic and diet therapies for EoE and will facilitate meaningful treatment comparisons and improve the quality of data synthesis.

Endoscopic Features and Eosinophil Density Are Associated with Food Impaction in Adults with Esophageal Eosinophilia.

BACKGROUND AND AIMS: Food impaction has been described in both eosinophilic esophagitis and proton pump inhibitor-responsive esophageal eosinophilia. The association between endoscopic/histologic features of esophageal eosinophilia and food impaction remains unclear. We aimed to identify clinical, endoscopic, and histologic findings associated with a history of food impaction in esophageal eosinophilia. METHODS: This was a retrospective cohort study of adult esophageal eosinophilia patients at a tertiary center in 6/2005-10/2014. Only patients with ≥15 eosinophils/high-power field on mucosal biopsies were included. Demographics, comorbidities, symptoms, endoscopic/histologic findings on initial endoscopy, and history of food impaction were reviewed. Statistical analyses were performed using Fisher's exact test (univariate) and forward stepwise logistic regression (multivariate). RESULTS: 400 patients (42 ± 14 years, 61 % male) were included, with 78 (20 %) having food impaction history. On univariate analyses, rings (62 vs 42 %, p = 0.003), erosions (12 vs 5 %, p = 0.03), eosinophil density on biopsy (40 [IQR = 30-50] vs 30 [IQR = 15-50], p = 0.004), and dysphagia (88 vs 62 %, p < 0.0001) were more prevalent among patients with food impaction history, while heartburn (10 vs 33 %, p < 0.0001) and abdominal pain (1 vs 12 %, p = 0.002) were less common. On multivariate analysis, rings (OR 2.6, p = 0.002), erosions (OR 3.2, p = 0.02), and eosinophil density (ß-coefficient = 0.01, p = 0.04) remained associated with food impaction. CONCLUSIONS: Findings of rings and erosions on endoscopy and increased eosinophil density on histology were independently associated with a history of food impaction in adult esophageal eosinophilia patients. Food impaction may result from both active inflammation (erosions and increased eosinophil density) and chronic fibrostenotic changes (rings).

Desensitizations for chemotherapy and monoclonal antibodies: indications and outcomes.

Acute infusion reactions to both chemotherapeutic agents and humanized monoclonal antibodies can occur, which may limit therapeutic options for treatment of malignancies and chronic inflammatory diseases. Many of these acute infusion reactions are consistent with a type I hypersensitivity reaction, including anaphylaxis. If a patient experiences a significant acute infusion reaction, often the recommendation is to discontinue the medication and find an alternative agent. However, the "second-line" agent may be more toxic or inferior. If the reaction is likely a type I or type IV hypersensitivity reaction, one option is to undergo desensitization to the offending drug. Drug desensitization is the process of readministering a needed drug in incremental doses over hours or days until a full therapeutic dose is tolerated. This article will review the current literature on indications and outcomes for drug desensitization in the management of allergy to either chemotherapeutic agents or monoclonal antibodies.

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.

The Cost-Effectiveness of Omalizumab for Treatment of Food Allergy.

BACKGROUND: Omalizumab is an anti-IgE therapy newly approved by the Food and Drug Administration for allergen agnostic treatment of single or multiple food allergies in patients aged 1 year or older. OBJECTIVE: Evaluate the cost-effectiveness of omalizumab as a food allergy treatment. METHODS: We evaluated health and economic outcomes in Markov cohorts of simulated food allergic infants randomized to receive omalizumab using a 15-year horizon. Monte Carlo simulation was used (n = 40,000 subjects) to evaluate cost-effectiveness from a societal perspective, incorporating both a family-level and individual-level analysis. We included family-level analysis to incorporate a broad perspective for health utility change, given treatment effects likely benefit all parties at home (eg, caregivers, siblings), not just the patient, representing the sum of changes in all such persons. Supplemental analyses explored lower omalizumab cost and home initiation. We performed deterministic and probabilistic sensitivity analyses. RESULTS: In the family-level cohort analysis, omalizumab exceeded cost-effectiveness thresholds ($185,183/quality-adjusted life-years [QALY]). In a comparison of the omalizumab strategy (OMA) with the non-omalizumab strategy, the cost of OMA exceeded the non-omalizumab strategy ($315,020 vs $136,609) with greater incremental effectiveness (12.668 vs 11.699 QALY). In the individual-level analysis, the cost-effectiveness of OMA was $573,698/QALY. In base-case assessments, OMA was cost-effective (willingness to pay, $100,000/QALY) at a health state utility (HSU) improvement of 0.265. The value-based cost of OMA ranged from $14,166 to $23,791 when it was considered at the individual and family-unit levels. Requiring OMA administration in the clinic was not cost-effective (incremental cost-effectiveness ratio, $260,239). CONCLUSIONS: In the base case and at current pricing, omalizumab is not cost-effective, but it could be at a lower retail price or when use creates large health utility shifts in the family and patient.

A Media Advocacy Toolkit for the Allergist-Immunologist.

For clinicians involved in improving healthcare for patients with allergic and immunologic conditions, advocacy on a broader level through public outreach is key to advancing value-based care. In this article, we provide a toolkit of strategies and resources that can be used to raise public awareness of important issues through various mediums, including podcasts and social media, newspapers, testimonies, presentations, and interviews. A simple approach to effective media interactions is described using the acronym "RATIO," which stands for Research, Audience, Targeted topic, Interview rephrasing, and Optimism. The acronym also reminds the person who is presenting information that only a fraction of what is discussed will be recalled, and an even smaller proportion will be implemented. Key points should be made early. Examples of key talking points are provided for selected topics, including food allergy, anaphylaxis, asthma, rhinitis, and broader healthcare advocacy.

Pharmacoequity and Biologics in the Allergy Clinic: Providing the Right Care, at the Right Time, Every Time, to Everyone.

Pharmacoequity refers to equity in access to pharmacotherapy for all patients and is an especially large barrier to biologic agents in patients with allergic diseases. Value-based care models can prompt clinicians to address social determinants of health, promoting pharmacoequity. Pharmacoequity is influenced by numerous factors including socioeconomic status, which may be mediated through insurance status, educational attainment, and access to specialist care. In addition to lower socioeconomic status, race and ethnicity, age, locations isolated from care systems, and off-label indications for biologic agents all constitute barriers to pharmacoequity. Whereas pharmaco-inequity is more apparent for expensive biologics, it also affects many other allergy treatments including epinephrine autoinjectors and SMART for asthma. Current programs aimed at alleviating cost barriers are imperfect. Patient assistance programs, manufacturer-sponsored free drug programs, and rebates often increase the complexity of care, with resultant inequity, particularly for patients with lower health literacy. Ultimately, single silver-bullet solutions are elusive. Long-term improvement instead requires a combination of research, advocacy, and creative problem-solving to design more intelligent and efficient systems that provide timely access to necessary care for every patient, every time.

An International Delphi Consensus on the Management of Pollen-Food-Allergy Syndrome: A Work Group Report of the AAAAI Adverse Reactions to Foods Committee.

BACKGROUND: Pollen-food-allergy syndrome (PFAS) is common among patients with allergic rhinitis. Treatment recommendations for patients with PFAS remain variable. OBJECTIVE: To develop consensus recommendation statements for managing patients with PFAS. METHODS: An international panel of allergists, researchers, and nutritionists with an interest in PFAS from 25 different institutions across 11 countries convened and a list of statements was written by 3 authors. The RAND/University of California Los Angeles methodology was adopted to establish consensus on the statements. RESULTS: After 2 Delphi rounds, a consensus was reached on 14 statements. The panel agreed that patients with PFAS would benefit from counseling on the nature and basis of PFAS and the rare chance of more severe systemic reactions and their recognition. The panel agreed on avoiding the raw food responsible for the index reaction, but not potentially cross-reactive fruits/vegetables based on the responsible food of the index reaction. Epinephrine autoinjectors should be recommended for patients with PFAS who experienced severe symptoms (beyond the oropharynx) or for patients considered at risk for severe reactions. The panel agreed that the benefit of allergen immunotherapy remains unclear and that PFAS should not be considered the primary indication for such intervention. CONCLUSIONS: We developed consensus statements regarding counselling patients about the nature and severity of PFAS, potential risk factors, dietary avoidance, epinephrine autoinjector prescription, and allergen immunotherapy consideration for patients with PFAS.

Overlapping Transcriptional Profile in Proton Pump Inhibitor Responsive and Nonresponsive Eosinophilic Esophagitis.

INTRODUCTION: We compared esophageal mucosal gene transcript expression in proton pump inhibitor (PPI) responsive (PPI-R) eosinophilic esophagitis (EoE), PPI nonresponsive (PPI-NR) EoE, and healthy controls. METHODS: Transcript expression in midesophagus biopsies was determined using NanoString and a custom panel of EoE-specific genes. The top upregulated and downregulated genes with ≥2-fold difference in expression and statistically significant ( P < 0.05) were identified. RESULTS: Nearly all the top upregulated (17 of 20) and downregulated (5 of 5) genes in EoE, compared with healthy controls, were shared between the PPI-R and PPI-NR groups. DISCUSSION: Esophageal mucosal transcript expressions are remarkably similar in PPI-R EoE and PPI-NR EoE compared with healthy controls.

Anaphylaxis in the Radiology Suite.

Contrast media are crucial for modern medical imaging. Contrast agents are generally well tolerated. However, patients may present with adverse reactions, which can be divided into pharmacological effects or hypersensitivity reactions. We present a vignette of a patient with a past history of urticaria after radiocontrast media exposure for coronary angiography. He returns for evaluation for radiocontrast media because he needs another coronary angiography. There are no validated methods for predicting such reactions yet. Mechanisms behind adverse contrast media reactions are still not well understood. Because of unknown contrast agent, the patient was successfully pretreated with corticosteroids and an H1 antihistamine.

Current Knowledge and Management of Hypersensitivity to Perioperative Drugs and Radiocontrast Media.

Perioperative anaphylaxis is an iatrogenic clinical condition, most often after anesthetic induction. Several mechanisms are implicated, including IgE- and non-IgE-mediated mechanisms. Perioperative anaphylaxis tends to be severe and has a higher mortality rate than anaphylaxis in other settings. This is partly due to factors that impair early recognition of anaphylaxis. Neuromuscular blocking agents, latex containing products, and antibiotics are the most common etiology. Chlorhexidine and dyes are increasingly culprits. The newest emerging cause is sugammadex, which is used for reversal of the effects of steroidal neuromusclar agents, such as rocuronium. Latex-induced allergy is becoming less common than in the 1980s due to primary and secondary prevention measures. Serum tryptase levels during the time of anaphylaxis and skin testing to suspected agents as an outpatient are necessary to confirm the diagnosis. Management includes epinephrine and aggressive fluid therapy. With radiocontrast media allergy, patients with a history of immediate hypersensitivity reactions to radiocontrast media should receive steroid and antihistamine premedication before re-exposure. Because IgE-mediated anaphylaxis to radiocontrast media is rare, there is a universal consensus that routinely skin testing all patients with a past reaction is not effective.