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Background: Total knee arthroplasty (TKA) represents a major national health expenditure. The last decade has seen a surge in robotic-assisted TKA (roTKA); however, literature on the costs of roTKA as compared to conventional TKA (cTKA) is limited. The purpose of this study was to assess the costs associated with roTKA as compared to cTKA. Methods: This was a retrospective cohort cost-analysis study of patients undergoing primary, elective roTKA or cTKA from July 2020 to March 2021. Time-driven activity-based costing (TDABC) was used to determine granular costs. Patient demographics, medical/surgical details, and costs were compared. Results: A total of 2058 TKAs were analyzed (1795 cTKAs and 263 roTKAs). roTKA patients were more often male (50.2% vs 42.3%; P = .016), and discharged home (98.5% vs 93.7%; P = .017), and had longer operating room (OR) time (144.6 vs 130.9 minutes; P < .0001), and lower length of stay (LOS) (1.8 vs 2.1 days; P < .0001). roTKA costs were 2.17× greater for supplies excluding implant (P < .0001), 1.18× for total supplies (P < .0001), 1.12× for OR personnel (P < .0001), and 1.05× for total personnel (P = .0001). Implant costs were similar (P = .076), but 0.98× cheaper for post-anesthesia care unit personnel (P = .018) and 0.84× for inpatient personnel (P < .0001). Overall hospital costs for roTKA were 1.10× more than cTKA (P < .0001). Conclusion: roTKA had higher total hospital costs than cTKA. Despite a lower LOS, the longer OR time with higher supply and personnel costs resulted in a costlier procedure. Understanding the costs of roTKA is essential when considering the value (ie, outcomes per dollars spent) of this modern technology.

Purpose of Review: To share important highlights on the management of anaphylaxis from the latest 2023 practice parameter., Recent Findings: The 2023 Allergy Immunology Joint Task Force on Practice Parameters (JTFPP) anaphylaxis practice parameter provides updated anaphylaxis guidance. Criteria for the diagnosis of anaphylaxis are reviewed. The parameter highlights that while anaphylaxis is not more severe in younger children, age-specific symptoms can vary. Activation of emergency medical services may not be required in patients who experience prompt resolution of symptoms following epinephrine use and caregivers are comfortable with observation. For children weighing <15 kg, the anaphylaxis parameter suggests the clinician may prescribe either the 0.1 mg or the 0.15 mg epinephrine autoinjector, with the 0.3 mg autoinjector prescribed for those weighing 25 kg or greater. In patients with heart disease, discontinuing or changing beta blockers and/or angiotensin converting enzyme inhibitors may pose a larger risk for worsened cardiovascular disease compared with risk for severe anaphylaxis with medication continuation. Furthermore, in patients with a history of perioperative anaphylaxis, shared decision-making based on diagnostic testing and clinical history is recommended prior to repeat anesthesia use. Beyond the recent parameter update, novel contemporary therapies can decrease risk of community anaphylaxis., Summary: The 2023 JTFPP Anaphylaxis Guidelines offer up-to-date guidance for the diagnosis and management of anaphylaxis in infants, children, and adults., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: To discuss if all patients who use self-injectable epinephrine outside the hospital setting require immediate emergency care., Recent Findings: Prior to 2023, anaphylaxis management guidance universally recommended that patients who use self-injectable epinephrine outside of the hospital or clinic setting immediately activate emergency medical services and seek further care. Additional food-induced anaphylaxis management recommendations specified that all patients always carry 2 auto-injector devices and give a second dose of epinephrine if there was not immediate response within 5 min of injection. Patients presenting for emergency care after epinephrine are often observed for up to 4-6 h afterwards, even when completely asymptomatic. These management steps have lacked evidence for improving outcomes, and universal implementation of these approaches is not cost-effective as guidance for food allergic patients. Epinephrine pharmacokinetics and pharmacodynamics suggest that peak physiologic response is more likely to occur closer to 15 min than before 5 min, that few patients require a second dose of epinephrine as most stabilize within 15 min of use, that 60 min of observation after a patient stabilizes after epinephrine use may be adequate as patients infrequently have further sequelae, and that not everyone needs to carry 2 epinephrine auto-injectors on their person at all times. The most recent anaphylaxis practice parameter promotes a contextualized approach to these management questions, outlining the option for watchful waiting to gauge response to epinephrine before seeking emergency care, which has been proven as a more cost-effective management strategy. The recent updated anaphylaxis care guidelines support the evolution of anaphylaxis care, in that universal, immediate activation of emergency services is not required for using self-injectable epinephrine outside the hospital setting., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Dupilumab is a monoclonal antibody that targets the interleukin (IL)-4 receptor alpha subunit, thus blocking the effects of IL-4 and IL-13, and has shown efficacy in treating various conditions including asthma, atopic dermatitis, eosinophilic esophagitis, and others. Because of its immune modulatory effects, clinical trials that studied dupilumab did not allow patients to receive live vaccines during the clinical trials because of an abundance of caution, and thus package inserts recommend that patients who are being treated with dupilumab should avoid live vaccines. Because dupilumab is now approved for use in patients from 6 months of age for the treatment of atopic dermatitis, this reported contraindication is now posing a clinical dilemma for patients and clinicians., Objective: To perform a systematic review of literature on the safety and efficacy of vaccinations in patients who are receiving dupilumab and to provide expert guidance on the use of vaccines in patients who are receiving dupilumab., Methods: A systematic review of the literature was performed, and an expert Delphi Panel was assembled., Results: The available literature on patients who received vaccinations while using dupilumab overall suggests that live vaccines are safe and that the vaccine efficacy, in general, is not affected by dupilumab. The expert Delphi panel agreed that the use of vaccines in patients receiving dupilumab was likely safe and effective., Conclusion: Vaccines (including live vaccines) can be administered to patients receiving dupilumab in a shared decision-making capacity., Competing Interests: Disclosures J.A.L. served as consultant for ARS, Aquestive, Bryn, ALK, and Novartis and Co-Chair Joint Task Force for Practice Parameters; received research money to institution from DBV and adjudication for Abvie and Siolta. T.E.D. the project described was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH), under Award Number 2UL1TR001425 - 05A1; the content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. E.M.A. is and employee of Public Health Agency of Canada, but the views in any paper are her own and not those of Public Health Agency of Canada. Board member of the Canadian Society of Allergy and Clinical Immunology and Head of Allergy Section, Canadian Pediatric Society. A.A. received institutional funding (Novartis) and consultation/speaker fees (ALK, EPG Health, MJH, Adelphi, Genentech, FARE, and Medscape) and served as advisory board member (Ready, Set, Food; Novartis; and Genentech). K.G.B. received grants from NIH (R01AI150295), AHRQ (R01HS029319), and Thermo Fisher Scientific and royalties from UpToDate and is consulting for Denali Therapeutics. M.B. serves as investigator and advisory board member for Regeneron and Sanofi. N.M.C. serves as clinical investigator; received research support from AstraZeneca, Genentech, and Kenota Health; serves as advisor, consultant, and/or speaker for Amgen, ARS Pharma, AstraZeneca, Blueprint Medicines, Bryn Pharma LLC, Freed AI, Genentech, GSK, Hikma, Incyte, Novartis, Regeneron, and Sanofi. D.B.K.G. is a consultant for Novartis, Aquestive, CellDex, and Kokua; received clinical trials support from Genentech, Novartis, Pfizer, GSK, Merck, Regeneron, Allergy Therapeutics, Eli Lilly, and AstraZeneca and royalties from UpToDate. N.L.H. is a speaker for Adma Bio and Takeda; speaker and advisor for Pharming, Horizon/Amgen, Horizon; advisory board member and speaker for Pharmaceuticals/Amgen. M.G.L. received research money to institution from Regeneron. S.S.M. is speaker for Genentech, Regeneron/Sanofi, GSK, and AstraZeneca and received grant from Takeda. J.J.O. consultant/advisor: GSK, Aquestive, Amgen, and ARS; adjudication/DSMB: AZ, Novartis, GSK, Sanofi, and AbbVie; reviewer/editor and executive editor: Annals of Allergy, Asthma & Immunology; reviewer: UpToDate; executive editor: Medscape; research/grants: NIH. A.R. speakers bureau member for Sanofi/Regeneron, GSK, and AstraZeneca. N.L.R. received funding from the Jeffrey Modell Foundation (58293-I), the NIH (R21AI164100), and Takeda Pharmaceuticals; is consultant for Takeda, Pharming Healthcare, and CSL Behring; received royalties from Wolters Kluwer and UpToDate. L.S. is clinical investigator for Regeneron and DBV Technologies and advisor for Sanofi and Leo pharmaceuticals. M.S.S. is member and co-chair of the Joint Task Force on Practice Parameters; serves on the editorial board of The Journal of Allergy and Clinical Immunology In Practice; is an associate editor of Annals of Allergy, Asthma, and Immunology; serves on the board of directors of the American Academy of Allergy, Asthma, and Immunology (views expressed are his own); has participated in research that has received funding from DBV. J.M.S. received grant support from and is consultant for Regeneron/Sanofi. C.A.S. recipient of a AAAAI Foundation Faculty Development Award. The views expressed in this work are the responsibility of the authors and do not necessarily represent the official views of the AAAAI. D.R.S. is consultant to ARS. J.W. received research support from NIAID, Aimmune, DBV Technologies, and Siolta and consultancy fees from ALK Abello, DBV Technologies, and Novartis. M.J.G. is consultant for Aquestive; is a member of physician/medical advisory boards for DBV Technologies, Sanofi/Regeneron, Nutricia, Novartis, Acquestive, Allergy Therapeutics, AstraZeneca, ALK-Abello, Bryn, Genentech, and Prota; is an unpaid member of the scientific advisory council for the National Peanut Board and medical advisory board of the International Food Protein Induced Enterocolitis Syndrome Association; is a member of the Brighton Collaboration Criteria Vaccine Anaphylaxis 2.0 working group; is the senior associate editor for the Annals of Allergy, Asthma, and Immunology; is member of the Joint Taskforce on Allergy Practice Parameters; received honorarium for lectures from ImSci, Red Nucleus, Medscape, Paradigm Medical Communications, Kaplan, Food Allergy Research and Education, and multiple state/local allergy societies. The remaining authors have no conflicts of interest to report., (Copyright © 2024 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Atopic dermatitis (AD) is one of the main risk factors for infants in the development of food allergy. Oral immunotherapy (OIT) in early childhood has been found to be highly effective and safe in preschoolers with and without AD, especially in young infants. Delays in initiation of OIT in infants and children due to uncontrolled AD risk expansion of the number of foods children develop allergy to through unnecessary avoidance of multiple foods. Parents and caregivers may attribute eczema flares to OIT doses, which physicians usually ascribe to non-food triggers such as weather changes, psychological stress, and infection. There is a lack of published literature confirming OIT as a trigger of AD flares, and the degree to which OIT may be associated with AD flares needs to be further studied. We describe 8 case scenarios with varying degrees of AD flare before and during OIT. We propose management algorithms for children with preexisting concurrent AD and food allergy who are being considered for starting OIT and children with AD flares during OIT. Optimizing AD control strategies and providing adequate AD care education before starting OIT can reduce confusion for both parents and allergists if rashes arise during OIT, thus improving adherence to OIT., Competing Interests: Disclosures Dr Chua received honorarium from Pharmaniaga, Sanofi, and Menarini and is an advisory board member on maternal immunization against respiratory syncytial virus of Pfizer. Dr Mack has provided consultation and speaker services for DBV, ALK, and Alladapt and is an investigator for DBV, ALK-Abello, Dermavant, Arcutis, and Amgen. Dr Shaker is a member of the Joint Task Force on Practice Parameters, serves on the editorial board of the Journal of Allergy and Clinical Immunology In Practice, is an associate editor of Annals of Allergy, Asthma, and Immunology, and serves on the Board of Directors of the American Academy of Allergy, Asthma, and Immunology (views expressed are his own). Dr Chan has received research support from DBV Technologies; has been a member of advisory boards for Pfizer, Miravo, Medexus, Leo Pharma, Kaleo, DBV, AllerGenis, Sanofi Genzyme, Bausch Health, Avir Pharma, AstraZeneca, ALK, and Alladapt; and was co-lead of the CSACI oral immunotherapy guidelines., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Neuropsychiatric symptoms have long been acknowledged as a common comorbidity for individuals with allergic diseases. The proposed mechanisms for this relationship vary by disease and patient population and may include neuroinflammation and/or the consequent social implications of disease symptoms and management. We review connections between mental health and allergic rhinitis, atopic dermatitis, asthma, vocal cord dysfunction, urticaria, and food allergy. Many uncertainties remain and warrant further research, particularly with regard to how medications interact with pathophysiologic mechanisms of allergic disease in the neuroimmune axis. Proactive screening for mental health challenges, using tools such as the Patient Health Questionnaire and Generalized Anxiety Disorder screening instruments among others, can aid clinicians in identifying patients who may need further psychiatric evaluation and support. Although convenient, symptom screening tools are limited by variable sensitivity and specificity and therefore require healthcare professionals to remain vigilant for other mental health "red flags." Ultimately, understanding the connection between allergic disease and mental health empowers clinicians to both anticipate and serve the diverse physical and mental health needs of their patient populations., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Food allergy prevention has undergone a significant transformation over the past 3 decades. This review provides an overview of the evolution of food allergy prevention, highlighting changes in guidance, cost-effectiveness of prevention, the role of shared decision-making, and the emergence of oral immunotherapy for those in whom primary prevention fails. Changes to food allergy prevention over recent decades can be conceptualized into five epochs, which have followed a general trend of loosening restrictions on the allergen introduction timeline. These epochs are characterized by significant maternal and infant dietary restrictions in the "universal avoidance epoch"(-1990), loosened maternal diet restrictions in the "infant avoidance epoch" (1990-2000), a time-bound allergen introduction schedule in the "stratified avoidance epoch" (2000-2010), retraction of recommendations in the "corrective retraction epoch" (2010-2015), and endorsement of early allergen introduction in the "early introduction epoch" (2015-present), the start of which is marked by the 2015 Learning Early About Peanut study. In hindsight, it is clear that certain recommendations from previous decades were not the best course of action. A no-screening early introduction approach to food allergy prevention is both cost-effective and beneficial to patient quality of life., (Copyright © 2024, The Author(s). Published by OceanSide Publications, Inc., U.S.A.)

Anaphylaxis is a systemic allergic reaction that may be severe and life-threatening. With more than a dozen anaphylaxis definitions proposed over the past several decades and several diagnostic criteria in circulation, there is a need for a multinational consensus definition to simplify management across specialties. Anaphylaxis diagnostic criteria are more alike than they are different, and approaches of the National Institute of Allergy and Infectious Disease, World Allergy Organization, and Brighton Collaborative help to add granularity and perspective to patient management. Anaphylaxis occurs across a spectrum of severity within populations, although, among individual patients, there is some evidence to suggest more consistency for an individual allergen. Still, severity is influenced by a number of factors that demonstrate variability: factors that relate to allergen triggers, patient characteristics, and treatments received. Severity of anaphylaxis impacts management, and recent guidelines provide approaches that consider individual factors to inform both strong and conditional recommendations. Conditional recommendations serve as navigational signals for shared decision-making when patient expertise is leveraged to inform individual preferences and values together with clinician expertise in anaphylaxis management to provide patient care bespoke to each patient. As novel approaches to both prevention and treatment of anaphylaxis emerge, an understanding of the significance of strong and conditional recommendations becomes critical to providing individualized and appropriate care for patients at risk for anaphylaxis., (Copyright © 2024, The Author(s). Published by OceanSide Publications, Inc., U.S.A.)

Allergist-immunologists face significant challenges as experts in an ever-evolving field of neuroimmunology. Among these challenges is the increasingly frequent need to counsel patients with suspected mast cell activation disorders about perceived comorbidities, which may include hypermobile Ehlers-Danlos syndrome, amplified pain syndrome, fibromyalgia, burning sensation syndromes, migraines, irritable bowel syndrome, and postural orthostatic tachycardia syndrome. Patients may experience comorbid anxiety, panic disorder, and depression associated with disturbed sleep, fatigue, and cognitive impairment that often worsen when their physical symptoms increase in severity. These conditions may mimic mast cell activation disorders and are emotionally taxing for patients and clinicians because they are often accompanied by vague diagnostic courses, perceived unmanageability, social stigma, and significant impairment in quality of life. Combined with relatively poorly researched therapies, it is no surprise that clinicians may feel overwhelmed or find it difficult to provide consistently compassionate care for this population. In this article, we review available therapies for these conditions, which run the gamut from physical therapy to antidepressants to multimodal pain control. We highlight the benefit of multidisciplinary care within the primary care home, which includes an important role by the allergist-immunologist. By outlining simple approaches to initial treatment, we hope to empower clinicians with the tools needed to curb emotional burnout and embrace this patient population with compassion., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: To review the updated 2023 Allergy Immunology Joint Task Force on Practice Parameters (JTFPP) GRADE and Institute of Medicine (IOM) Based Guidelines for the management of atopic dermatitis., Recent Findings: Topical corticosteroids and/or calcineurin inhibitors are recommended in individuals with atopic dermatitis refractory to moisturizer alone and may be used to maintain remission after acute flare control is achieved. Calcineurin inhibitors are a class of immunosuppressants used to effectively manage different autoimmune disorders. Bleach baths and allergen immunotherapy may be beneficial for individuals with moderate-to-severe disease, while elimination diets, azathioprine, methotrexate, mycophenolate, and systemic corticosteroids are not recommended. Dupilumab is strongly recommended for refractory atopic dermatitis. Oral Janus kinase (JAK) inhibitors carry significant risks; however, this class of medicines may be considered in cases of severe or refractory atopic dermatitis with intolerance to dupilumab. Patient preferences regarding cost, availability, feasibility, and tolerability should be integrated into all treatment plans using a shared decision-making approach., Summary: The 2023 JTFPP Atopic Dermatitis Guidelines offer up-to-date guidance for the management of atopic dermatitis of varying severity in infants, children, and adults., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Adverse events occur in all fields of medicine, including allergy-immunology, in which allergen immunotherapy medical errors can cause significant harm. Although difficult to experience, such errors constitute opportunities for improvement. Identifying system vulnerabilities can allow resolution of latent errors before they become active problems. We review key aspects and frameworks of the medical error response, acknowledging the fundamental responsibility of clinical teams to learn from harm. Adverse event response comprises 4 major phases: (1) event recognition and reporting, (2) investigation (for which root cause analysis can be helpful), (3) improvement (inclusive of the plan-do-study-act cycle), and (4) communication and resolution. Throughout the process, clinician wellness must be maintained. Adverse event prevention should be prioritized, and a human factors engineering approach can be useful. Quality improvement tools and approaches complement one another and together offer a meaningful avenue for error recovery and prevention., Competing Interests: Disclosures Dr Bansal serves on the board of directors of the American Academy of Allergy, Asthma and Immunology and American Board of Allergy and Immunology (views expressed are her own). She has participated in advisory boards and served as a speaker for ALK, AstraZeneca, Bryn, Sanofi Genzyme/Regeneron, Takeda, CSL, Pharming, and Glaxo Smith Kline. Dr Shaker is a member and cochair of the Joint Task Force on Practice Parameters, serves on the editorial board of The Journal of Allergy and Clinical Immunology In Practice, is an associate editor of Annals of Allergy, Asthma & Immunology, serves on the board of directors of the American Academy of Allergy, Asthma, and Immunology (views expressed are his own), and has participated in research that has received funding from DBV. Dr Bradley is the director of Graduate Medical Education Quality and Safety, Dartmouth Health. The remaining authors have no conflicts of interest to report., (Copyright © 2024 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Allergist-immunologists use serologic peanut allergy testing to maximize test sensitivity and specificity while minimizing cost and inconvenience. Recent advances toward this goal include a better understanding of specific IgE (sIgE) and component testing, epitope-sIgE assays, and basophil activation testing. Predicting reaction severity with serologic testing is challenged by a range of co-factors that influence reaction severity, such as the amount and form of any allergen consumed and comorbid disease. In 2020, the Allergy Immunology Joint Task Force on Practice Parameters recommended Ara h 2-sIgE as the most cost-effective diagnostic test for peanut allergy because of its superior performance, when compared with skin prick testing and serum IgE. Basophil activation testing, a functional test of allergic response not evaluated in the Joint Task Force on Practice Parameters guideline, is a promising option for both allergy diagnosis and prognosis. Similarly, epitope-sIgE testing may improve prediction of reaction thresholds, but further validation is needed. Despite advances in food allergy testing, many of these tools remain limited by cost, accessibility, and feasibility. In addition, there is a need for further research on how atopic dermatitis may be modifying serologic food allergy severity assessments. Given these limitations, allergy test selection requires a shared decision-making approach so that a patient's values and preferences regarding financial impact, inconvenience, and psychological effects are considered in the context of clinician expertise on the timing and use of optimized testing., Competing Interests: Disclosures Dr Golden is a consultant for Novartis, Aquestive, and Kokua and has received clinical trials support from Genentech, Novartis, Pfizer, GlaxoSmithKline, Merck, Regeneron, and AstraZeneca. Dr Brough reports receiving research grants from the NIH (NIAAD) and speaker fees from DBV Technologies. Dr Santos reports receiving grants from Medical Research Council (MR/M008517/1; MC/PC/18052; and MR/T032081/1), Food Allergy Research and Education, the Immune Tolerance Network/National Institute of Allergy and Infectious Diseases (NIAID and NIH), Asthma UK (AUK-BC-2015-01), BBSRC, Rosetrees Trust, and the NIHR through the Biomedical Research Centre award to Guy's and St Thomas' NHS Foundation Trust, during the conduct of the study; receiving personal fees from Thermo Scientific, Nutricia, Infomed, Novartis, Allergy Therapeutics, and Buhlmann; and receiving research support from Buhlmann and Thermo Fisher Scientific through a collaboration agreement with King's College London. Dr Shaker is a member and co-chair of the Joint Task Force on Practice Parameters; serves on the editorial board of The Journal of Allergy and Clinical Immunology In Practice; is an associate editor of Annals of Allergy, Asthma & Immunology; serves on the board of directors of the American Academy of Allergy, Asthma, and Immunology (views expressed are his own); and has participated in research that has received funding from DBV. Dr Conway has no conflicts of interest to report., (Copyright © 2024 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Disclosures Dr Shaker is a member and co-chair of the Joint Task Force on Practice Parameters; serves on the editorial board of The Journal of Allergy and Clinical Immunology In Practice; is an associate editor of Annals of Allergy, Asthma, and Immunology; serves on the board of directors of the American Academy of Allergy, Asthma, and Immunology (views expressed are his own); and has participated in research that has received funding from DBV. Dr Nowak-Wegrzyn receives research support from the National Institutes of Health National Institute of Allergy and Infectious Diseases, DBV Technologies, and Siolta Therapeutics; speaking fees from Nestle, Danone, Medscape, and Genentech; and royalties from UpToDate, serves as an Associate Editor for the Annals of Allergy, Asthma, and Immunology and Director of the American Academy of Allergy, Asthma, and Immunology Board, and is the Chair of the Medical Advisory Board of the International Food protein-induced enterocolitis syndrome Association.

Purpose of Review: In the last 5 years, several new inborn errors of immunity (IEI) have been described, especially in the areas of immune dysregulation and autoinflammation. As a result, the clinical presentation of IEIs has broadened. We review the heterogeneous presentation of IEIs and detail several of the recently described IEIs with a focus on the noninfectious manifestations commonly seen., Recent Findings: IEIs may present with early onset and/or multiple autoimmune manifestations, increased risk for malignancy, lymphoproliferation, severe atopy, autoinflammation and/or hyperinflammation. Because of this, patients can present to a wide array of providers ranging from primary care to various pediatric subspecialists. The International Union of Immunological Societies (IUIS) expert committee has created a phenotypic classification of IEIs in order to help clinicians narrow their evaluation based on the laboratory and clinical findings., Summary: Both primary care pediatricians and pediatric subspecialists need to be aware of the common clinical features associated with IEI and recognize when to refer to allergy-immunology for further evaluation. Early diagnosis can lead to earlier treatment initiation and improve clinical outcomes for our patients., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: Disclosures Dr Shaker is a member and co-chair of the Joint Task Force on Practice Parameters; serves on the editorial board of The Journal of Allergy and Clinical Immunology In Practice; is an associate editor of Annals of Allergy, Asthma & Immunology; serves on the board of directors of the American Academy of Allergy, Asthma, & Immunology (views expressed are his own); and has participated in research that has received funding from DBV. Dr Golden is a consultant for Novartis, Aquestive, and Kokua; and has received clinical trial support from Genentech, Novartis, Pfizer, GlaxoSmithKline, Merck, Regeneron, and AstraZeneca. Dr Lieberman is a member and co-chair of the Joint Task Force on Practice Parameters; is an associate editor of Annals of Allergy, Asthma & Immunology; serves on the board of the American Board of Allergy and Immunology; serves as an advisor consultant for ARS, Bryn, and Aquestive; serves on the adjudication/DSMB for AbbVie and Siolta; and is an investigator (money to institution) for Novartis and DBV. Dr Greenhawt is a consultant for Aquestive; is a member of physician/medical advisory boards for DBV Technologies, Nutricia, Novartis, Aquestive, Allergy Therapeutics, AstraZeneca, ALK-Abello, Bryn, Genentech, and Prota; is an unpaid member of the scientific advisory council for the National Peanut Board and medical advisory board of the International Food Protein Induced Enterocolitis Syndrome Association; is a member of the Brighton Collaboration Criteria Vaccine Anaphylaxis 2.0 working group; is the senior associate editor for the Annals of Allergy, Asthma & Immunology; is a member of the Joint Taskforce on Allergy Practice Parameters; and has received honorarium for lectures from ImSci, Red Nucleus, Medscape, Paradigm Medical Communications, and multiple state/local allergy societies. Dr Lee is on the editorial boards of Pharmacology Research and Perspectives, Frontiers in Oncology, Frontiers in Pharmacology, Kidney and Blood Pressure Research, and BMC Medical Education. He is the owner and creator of Pharmacology World LLC which generates royalties.

Background: Viruses employ diverse strategies to interfere with host defense mechanisms, including the production of proteins that mimic or resemble host proteins. This study aimed to analyze the similarities between SARS-CoV-2 and human proteins, investigate their impact on virus-host interactions, and elucidate underlying mechanisms., Results: Comparing the proteins of SARS-CoV-2 with human and mammalian proteins revealed sequence and structural similarities between viral helicase with human UPF1. The latter is a protein that is involved in nonsense-mediated RNA decay (NMD), an mRNA surveillance pathway which also acts as a cellular defense mechanism against viruses. Protein sequence similarities were also observed between viral nsp3 and human Poly ADP-ribose polymerase (PARP) family of proteins. Gene set enrichment analysis on transcriptomic data derived from SARS-CoV-2 positive samples illustrated the enrichment of genes belonging to the NMD pathway compared with control samples. Moreover, comparing transcriptomic data from SARS-CoV-2-infected samples with transcriptomic data derived from UPF1 knockdown cells demonstrated a significant overlap between datasets., Conclusions: These findings suggest that helicase/UPF1 sequence and structural similarity might have the ability to interfere with the NMD pathway with pathogenic and immunological implications., (© 2023. The Author(s).)

The present study aims to simulate and design a near-Zero Energy neighborhood in one of the most significant industrial cities for reducing greenhouse gas emissions. For this building, biomass wastes are used for energy production, and also energy storage is provided using a battery pack system. Additionally, the Fanger model is used to assess the passengers' thermal comfort, and information on hot water usage is given. The transient performance of the aforementioned building is tested for one year using TRNSYS software, which was employed for this simulation. Wind turbines are considered electricity generators for this building, and any extra energy generated is stored in a battery pack for usage when the wind speed is insufficient and electricity is needed. Hot water is created using a biomass waste system and is kept in a hot water tank after being burned using a burner. A humidifier is utilized to ventilate the building, and a heat pump provides both the building's heating and cooling needs. The produced hot water is used to supply the residents' hot water. In addition, The Fanger model is considered and used for the assessment of occupants' thermal comfort. Matlab software is a powerful software used for this task. According to the findings, a wind turbine with a 6 kW generation capacity may supply the building's power needs while also charging the batteries beyond their initial capacity, and the building will have zero energy. Additionally, biomass fuel is used to give the building the required water which should be hot. On average, 200 g of biomass and biofuel are used per hour to maintain this temperature., Competing Interests: Declaration of competing interest The Authors Declare That There Is NO Conflict of Interest., (Copyright © 2023. Published by Elsevier Ltd.)

Food allergy (FA) is a growing issue worldwide. The United Kingdom and United States are high-income, industrialized countries with reported increases in FA prevalence over the past few decades. This review compares delivery of FA care in the United Kingdom and United States and each country's response to the heightened demand and disparities for FA services. In the United Kingdom, allergy specialists are scarce and general practitioners (GPs) provide most allergy care. Whereas the United States has more allergists per capita than the United Kingdom, there is still a shortage of allergy services owing to the greater reliance on specialist care for FA in America and wide geographic variation in access to allergist services. Currently, generalists in these countries lack the specialty training and equipment to diagnose and manage FA optimally. Moving forward, the United Kingdom aims to enhance training for GPs so they may provide better quality frontline allergy care. In addition, the United Kingdom is implementing a new tier of semi-specialized GPs and increasing cross-center collaboration through clinical networks. The United Kingdom and United States aim to increase the number of FA specialists, which is critical at a time of rapidly expanding management options for allergic and immunologic diseases requiring clinical expertise and shared decision-making to select appropriate therapies. While these countries aim to grow their supply of quality FA services actively, further efforts to build clinical networks and perhaps recruit international medical graduates and expand telehealth services are necessary to reduce disparities in access to care. For the United Kingdom in particular, increasing quality services will require additional support from the leadership of the centralized National Health Service, which remains challenging., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Malnutrition is prevalent in chronic hemodialysis (HD) patients. It increases mortality and negatively affects quality of life. This study aimed to assess the effect of intradialytic oral nutritional supplement (ONS) on nutritional markers in chronic HD patients with protein energy wasting (PEW)., Methods: This 3-month prospective, open-label, randomized controlled trial included 60 chronic HD patients with PEW. The intervention group (30 patients) received intradialytic ONS and dietary counseling, whereas the control group (30 patients) received only dietary counseling. Nutritional markers were measured at the beginning and end of the study., Results: The mean age of the patients was 54 ± 12.7 years, and that of the HD vintage was 64 ± 49.3 months. Compared to the control group, the intervention group showed a significant increase in serum albumin (p < 0.001), prealbumin (p < 0.001), cholesterol (p = 0.016), body mass index (BMI) (p = 0.019), serum creatinine/body surface area (BSA) (p = 0.016), and composite French PEW score (p = 0.002), as well as a significant decrease in high-sensitivity C-reactive protein (hs-CRP) (p = 0.001). The total iron binding capacity, normalized protein nitrogen appearance, and hemoglobin levels increased significantly in both groups., Conclusion: Intradialytic ONS and dietary counseling for three months were more effective than dietary counseling alone in terms of improving nutritional status and inflammation in chronic HD patients, as evidenced by increases in serum albumin, prealbumin, BMI, serum creatinine/BSA, composite French PEW score, and a decrease in hs-CRP., (© 2023. The Author(s).)

There is increased focus on the role of maternal interventions in the prevention of food allergy in infancy. There is no role for maternal dietary modifications during pregnancy or lactation, such as allergen avoidance, as a means of infant allergy prevention. Although exclusive breastfeeding is the recommended infant nutrition source globally, the effect of breastfeeding on infant allergy prevention remains unclear. There is emerging evidence that irregular cow's milk exposure (ie, infrequent formula supplementation) might increase the risk of cow's milk allergy. Although further studies are required, there is also emerging evidence that maternal peanut ingestion during breastfeeding along with early peanut introduction in infancy might have a preventive role. The effect of maternal dietary supplementation with vitamin D, omega-3, and prebiotics or probiotics remains unclear., Competing Interests: Declaration of interests EMA is an employee of Public Health Agency of Canada and the views expressed here are her own and not those of the institution. MSS serves on the editorial board of The Journal of Allergy and Clinical Immunology: In Practice; is an associate editor of Annals of Allergy, Asthma, and Immunology; is a member of the Joint Task Force on Practice Parameters, and has participated in research that has received funding from DBV Technologies. HAB receives research grant funding from the National Institutes of Health; is sub-investigator for DBV Technologies and Aimmune research studies, and has received speaker honoraria from DBV Technologies, GlaxoSmithKline, and Sanofi. ESC has received research support from DBV Technologies; has been a member of advisory boards for Pfizer, Miravo, Medexus, Leo Pharma, Kaleo, DBV Technologies, AllerGenis, Sanofi Genzyme, Bausch Health, Avir Pharma, AstraZeneca, and ALK; is on the executive board of the CSACI; is on the executive board of the Canadian Paediatric Society Allergy Section, and is a member of the health-care advisory board for Food Allergy Canada. MG is a consultant for Aquestive; is a member of physician and medical advisory boards for DBV Technologies, Sanofi/Regeneron, Nutricia, Novartis, Acquestive, Allergy Therapeutics, AstraZeneca, ALK-Abello, and Prota; is an unpaid member of the scientific advisory council for the National Peanut Board and medical advisory board of the International Food Protein Induced Enterocolitis Syndrome Association; is a member of the Brighton Collaboration Criteria Vaccine Anaphylaxis 2.0 working group; is the senior associate editor for the Annals of Allergy, Asthma, and Immunology, and is member of the Joint Taskforce on Allergy Practice Parameters. MG has received honorarium for lectures from ImSci, MedLearningGroup, RMEI Medical Education, and multiple state and local allergy societies. MG received past research support ending in 2020, from the Agency for Healthcare Quality and Research (K08-HS024599)., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: In the 5 years that have passed since the publication of the 2018 International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (ICAR-Allergic Rhinitis 2018), the literature has expanded substantially. The ICAR-Allergic Rhinitis 2023 update presents 144 individual topics on allergic rhinitis (AR), expanded by over 40 topics from the 2018 document. Originally presented topics from 2018 have also been reviewed and updated. The executive summary highlights key evidence-based findings and recommendation from the full document., Methods: ICAR-Allergic Rhinitis 2023 employed established evidence-based review with recommendation (EBRR) methodology to individually evaluate each topic. Stepwise iterative peer review and consensus was performed for each topic. The final document was then collated and includes the results of this work., Results: ICAR-Allergic Rhinitis 2023 includes 10 major content areas and 144 individual topics related to AR. For a substantial proportion of topics included, an aggregate grade of evidence is presented, which is determined by collating the levels of evidence for each available study identified in the literature. For topics in which a diagnostic or therapeutic intervention is considered, a recommendation summary is presented, which considers the aggregate grade of evidence, benefit, harm, and cost., Conclusion: The ICAR-Allergic Rhinitis 2023 update provides a comprehensive evaluation of AR and the currently available evidence. It is this evidence that contributes to our current knowledge base and recommendations for patient evaluation and treatment., (© 2023 The Authors. International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)

Potato ( Solanum tuberosum L.) and tomato ( S. lycopersicum L.) are the most economically important vegetable crops in Egypt and worldwide. The winter crop in Egypt is particularly prone to late blight caused by Phytophthora infestans . A total of 152 P. infestans isolates were isolated from the 2013, 2014, 2016 and 2018 winter crops with 82 isolates from potato, 69 from tomato and one isolate from eggplant ( S. melongena L.). All isolates belonged to the A1 mating type with no evidence of A2 or self-fertile strains. The majority of isolates (53%) were sensitive to metalaxyl, 32% were intermediate and 15% were resistant. Variation in aggressiveness between three P. infestans isolates EG-005 (13&#95;A2) and EG-276 (23&#95;A1) from potato, and EG-237 (23&#95;A1) from eggplant was determined on tuber slices and leaflets of 10 potato cultivars. The eggplant isolate EG-237 showed higher sporulation capacity compared with the other tested isolates and was able to infect potato (Lady Rosetta cv) and tomato (Super Strain B cv). The simple sequence repeat (SSR) genotyping data showed that in contrast to our previous work (3-year period 2010-12) in which the proportion of 13&#95;A2 lineage was 35%, all isolates belonged to the 23&#95;A1 lineage. There was no evidence for the existence of the A2 mating type or 13&#95;A2 lineage even in the destroyed field crops of some cultivars (Cara, Bellini and Valor) that had been reported as resistant to 23&#95;A1. The data have been submitted into the Euroblight database to allow temporal and spatial genetic diversity to be examined in comparison with other regional P. infestans populations. The AVR2 and AVR2-like RXLR effector genes were amplified and sequenced. In the avirulent AVR2 gene, only one heterozygous SNP was detected at position 31 in the N terminus in six isolates out of eleven, whereas two heterozygous SNPs were detected at position 29 in the N-terminus and ninety-two in the C- terminus of the AVR2-like gene. This suggests that changes in the previously reported virulence profile of 23&#95;A1 are not related to commercial cultivars carrying the R2 gene. In addition, this is the first report of P. infestans on eggplant in Egypt.

Nicotine dependence (ND) and visceral adiposity are emerging as independent risk factors for cardiovascular diseases, including carotid artery stenosis (CAS). This study aimed to determine the relationship between ND and the contribution of abdominal fat to the onset of CAS, which is indicated by a luminal narrowing of at least 60% as determined by duplex and/or Doppler ultrasound. We prospectively collected data from 60 patients with CAS and 60 age- and gender-matched healthy subjects. The Fagerström Test for Nicotine Dependence (FTND), a common research tool, was used in the study. The original questionnaire was designed to gather social and demographic data. Anthropometric measurements, visceral adiposity index (VAI), and lipid accumulation products (LAP) were used to assess obesity. Most patients showed a high or mild-moderate degree of ND: 46.67% and 35%, respectively. The median visceral adiposity index (VAI) and lipid accumulation product (LAP) in patients was 3.92 and 32.83, respectively. Prolonged smoking duration, increased intensity, and high ND are hallmarks of CAS patients., Competing Interests: The authors declare no conflict of interest., (©2023 JOURNAL of MEDICINE and LIFE.)

An updated edition of the International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (ICAR:AR) has recently been published. This consensus document, which included the participation of 87 primary authors and 40 additional consultant authors, who critically appraised evidence on 144 individual topics concerning allergic rhinitis, provides guidance for health care providers using the evidence-based review with recommendations (EBRR) methodology. This synopsis highlights topical areas including pathophysiology, epidemiology, disease burden, risk and protective factors, evaluation and diagnosis, aeroallergen avoidance and environmental controls, single and combination pharmacotherapy options, allergen immunotherapy (subcutaneous, sublingual, rush, cluster), pediatric considerations, alternative and emerging therapies, and unmet needs. Based on the EBRR methodology, ICAR:AR includes strong recommendations for the treatment of allergic rhinitis: (1) for the use of newer generation antihistamines compared with first-generation alternatives, intranasal corticosteroid, intranasal saline, combination therapy with intranasal corticosteroid plus intranasal antihistamine for patients not responding to monotherapy, and subcutaneous immunotherapy and sublingual tablet immunotherapy in properly selected patients; (2) against the use of oral decongestant monotherapy and routine use of oral corticosteroids., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

These evidence-based guidelines support patients, clinicians, and other stakeholders in decisions about the use of intranasal corticosteroids (INCS), biologics, and aspirin therapy after desensitization (ATAD) for the management of chronic rhinosinusitis with nasal polyposis (CRSwNP). It is important to note that the current evidence on surgery for CRSwNP was not assessed for this guideline nor were management options other than INCS, biologics, and ATAD. The Allergy-Immunology Joint Task Force on Practice Parameters formed a multidisciplinary guideline panel balanced to include the views of multiple stakeholders and to minimize potential biases. Systematic reviews for each management option informed the guideline. The guideline panel used the Grading of Recommendations Assessment, Development and Evaluation approach to inform and develop recommendations. The guideline panel reached consensus on the following statements: (1) In people with CRSwNP, the guideline panel suggests INCS rather than no INCS (conditional recommendation, low certainty of evidence). (2) In people with CRSwNP, the guideline panel suggests biologics rather than no biologics (conditional recommendation, moderate certainty of evidence). (3) In people with aspirin (nonsteroidal anti-inflammatory drug)-exacerbated respiratory disease, the guideline panel suggests ATAD rather than no ATAD (conditional recommendation, moderate certainty of evidence). The conditions for each recommendation are discussed in the guideline., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Purpose: Clubfoot is among the most common musculoskeletal congenital anomalies. Poor understanding of clubfoot can cause lack of awareness that leads to complications in treating this condition because of late medical intervention. This is considered as a significant public health problem, especially in communities where the burden of clubfoot deformity remains unrecognized. We assessed the level of awareness and knowledge on clubfoot among residents of rural areas and determined the knowledge and attitudes of the public toward the risk factors and general consequences of clubfoot., Methods: This cross-sectional study, conducted from January to July 2021, included the general population of small city and rural area residents. The participants completed a self-administered survey on the web. The questionnaire was pre-tested in a pilot study to ensure comprehension and ease of administration., Results: Altogether, 41.6% of the participants recognized the scientific name of clubfoot in their native language, whereas 38.9% identified the disorder after they were shown a photograph of it. The most recognized risk factors of clubfoot according to the participants were family history (52.2%), complicated pregnancy (46.5%), and medications (43.4%). Only 8.8% of the participants considered casting the initial treatment of clubfoot., Conclusion: An individual's residential area plays a role in their level of awareness concerning clubfoot. Our results suggest that many educational interventions for clubfoot must be provided in rural areas, particularly regarding therapeutic options and plans of care., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Family Medicine and Primary Care.)

In this research, rabbit femurs were implanted with CP Ti screws coated with a combination of CaCO 3 and nanohydroxyapatite, and the effect on osseointegration was assessed using histological and histomorphometric examination at 2 and 6 weeks. CaCO 3 and nanohydroxyapatite were combined with the EPD to coat the surfaces of the CP Ti screws. The femurs of five male rabbits were implanted with coated and uncoated implant screws. Healing time was divided into two groups (2 and 6 weeks). After 2 and 6 weeks of implantation, the histological examination revealed an increase in the growth of bone cells for coated screws, and the histomorphometric analysis revealed an increase in the percentage of new bone formation (after 6 weeks, 5.08% for coated implants and 3.66% for uncoated implants). In addition, the uncoated implant, the CP Ti implant coated with a combination of CaCO 3 and nanohydroxyapatite, stimulated early bone development after two weeks and mineralization and maturation after six weeks., Competing Interests: The authors declare no conflict of interest., (©2022 JOURNAL of MEDICINE and LIFE.)

Purpose: Osteoarthritis (OA) patients demonstrated higher Osteopontin (OPN) plasma, serum, and synovial fluid concentrations than healthy individuals. In the present study, we aimed to investigate whether OPN could be used as a diagnostic or prognostic marker for OA symptom/disease severity., Methods: Using Web of Science, PubMed, Scopus, and Embase, we conducted a systematic review and meta-analysis of studies that measured OPN levels in OA patients' plasma, serum, or synovial fluid. After setting the eligibility criteria, data extraction, and quality assessment of the identified studies, we performed statistical analysis using Revman 5.4 and Open Meta analyst., Results: OPN has been found to be associated with advanced knee joint damage in OA patients. In addition, higher expression of OPN is thought to be associated with disease progression. Nevertheless, further studies should examine the role of other markers of chronic bone damage, such as leptin and sclerostin. This systematic review and meta-analysis included 14 studies with a total of 776 cases and 530 controls. OPN was significantly elevated in osteoarthritis patients' plasma, serum, and synovial fluid samples, with significant heterogeneity between studies., Conclusion: We recommend that OPN plasma and synovial fluid levels be measured as a diagnostic and prognostic marker to determine the severity of OA symptoms., Competing Interests: Declaration of Competing Interest None of the authors has any potential financial conflict of interest related to this manuscript., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The influence of allergist management on peanut allergy (PA)-related health care utilization is unknown., Objective: To determine whether allergist care lowers PA costs., Methods: IBM MarketScan Commercial Claims and Encounters Database was analyzed for PA diagnosis/reaction-related codes (January 2010-June 2019) in patients 64 years or younger, with demographically matched non-PA food allergy controls (NPAFACs). Outcomes were measured and compared 12 months before/after first claim date., Results: Among 72,854 persons with PA (39,068 with ≥1 allergist visit, 53.6%), and 166,825 NPAFACs, the number of National Drug Codes and International Classification of Diseases, 10th Revision codes was higher for persons with PA with versus without an allergist visit during both baseline and follow-up (all P < .001). Persons with PA with versus without an allergist visit were prescribed epinephrine at significantly higher rates (RR, 1.67; P < .001). Rates of epinephrine claims, mean epinephrine costs, and proportion with peanut anaphylaxis were higher among the PA group with versus without an allergist visit (69.9% vs 63.3%; $676 vs $493, 48.9% vs 20.7%; all P < .001). The proportion with anaphylaxis episodes was higher in the PA group versus the NPAFAC group (53.1% vs 31.6%; P < .001). Total health care costs were higher in the NPAFAC group versus the PA group ($7863 vs $7261; P < .001) and lower for persons with PA with versus without an allergist visit ($6347 vs $8270; P < .001), with no significant differences in PA reaction-related costs between PA groups., Conclusions: Higher rates of anaphylaxis were seen among the PA group with versus without an allergist visit during the follow-up period (53.6% of overall PA group). Allergist care was associated with a reduction in total health care costs and higher rates of epinephrine prescription., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Sudden cardiac arrest (SCA) occurs in 0.4% of the general population and up to 6% or more of at-risk groups each year. Early CPR and defibrillation improves SCA outcomes but access to automatic external defibrillators (AEDs) remains limited., Methods: Markov models were used to evaluate the cost-effectiveness of a portable SMART (SMall AED for Rapid Treatment of SCA) approach to early SCA management over a life-time horizon in at-risk and not at-risk populations. Simulated patients ( n = 600,000) who had not received an implantable cardioverter defibrillator (ICD) were randomized to a SMART device with CPR prompts or non-SMART approaches. Annual SCA risk was varied from 0.2 to 3.5%. Analysis was performed in a US economy from both societal (SP) and healthcare (HP) perspectives to evaluate the number of SCA fatalities prevented by SMART, and SMART cost-effectiveness at a threshold of $100,000/Quality Adjusted Life Year (QALY)., Results: A SMART approach was cost-effective when annual SCA risk exceeded 1.51% (SP) and 1.62% (HP). The incremental cost-effectiveness ratios (ICER) were $95,251/QALY (SP) and $100,797/QALY (HP) at a 1.60% SCA annual risk. At a 3.5% annual SCA risk, SMART was highly cost-effective from both SP and HP [ICER: $53,925/QALY (SP), $59,672/QALY (HP)]. In microsimulation, SMART prevented 1,762 fatalities across risk strata (1.59% fatality relative risk reduction across groups). From a population perspective, SMART could prevent at least 109,839 SCA deaths in persons 45 years and older in the United States., Conclusions and Relevance: A SMART approach to SCA prophylaxis prevents fatalities and is cost-effective in patients at elevated SCA risk. The availability of a smart-phone enabled pocket-sized AED with CPR prompts has the potential to greatly improve population health and economic outcomes., Competing Interests: MSS has a family member who is employed by Altrix Medical, is a member of the Joint Taskforce on Allergy Practice Parameters, and serves as a member of the editorial boards of the Journal of Allergy and Clinical Immunology in Practice, the Annals of Allergy, Asthma, and Immunology, and the Journal of Food Allergy. EA is an employee of Public Health Agency of Canada (PHAC); the views expressed in this article are hers and not that of PHAC. JO declares the following: Research/Adjudication: AZ, GSK, Sanofi, Novartis; Consultant: GSK, AZ, Sanofi; Associate Editor: Annals of Allergy Asthma Immunology, AllergyWatch; Section Editor: Current Opinion of Allergy; Royalties: Up to Date; Board Liaison ABIM for ABAI. MS holds a patent related to a smart-phone enabled small AED and is employed by Altrix Medical. DF is employed by Altrix Medical. Altrix Medical's Smart AED is supported by the National Science Foundation under Grant No. 1842149 and under Cooperative Agreement No. 2026090. MG was supported by grant #5K08HS024599-02 from the Agency for Healthcare Quality and Research during the preparation of this manuscript; is an expert panel and coordinating committee member of the NIAID-sponsored Guidelines for Peanut Allergy Prevention; has served as a consultant for the Canadian Transportation Agency, Thermo Fisher, Intrommune, and Aimmune Therapeutics; is a member of physician/medical advisory boards for Aimmune Therapeutics, DBV Technologies, Sanofi/Genzyme, Genentech, Nutricia, Novatris, Kaleo Pharmaceutical, Nestle, Acquestive, Allergy Therapeutics, Pfizer, US World Meds, Allergenis, Aravax, and Monsanto; is a member of the scientific advisory council for the National Peanut Board; has received honorarium for lectures from Thermo Fisher, Before Brands, multiple state allergy societies, the ACAAI, the EAACI; is an associate editor for the Annals of Allergy, Asthma, and Immunology; and is a member of the Joint Taskforce on Allergy Practice Parameters. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shaker, Abrams, Oppenheimer, Singer, Shaker, Fleck, Greenhawt and Grove.)

Importance: Lifelong immunoglobulin replacement therapy (IRT) is standard-of-care treatment for congenital agammaglobulinemia but accrues high annual costs ($30 000-$90 000 per year) and decrements to quality of life over patients' life spans. Hematopoietic stem cell transplant (HSCT) offers an alternative 1-time therapy, but has high morbidity and mortality., Objective: To evaluate the cost utility of IRT vs matched sibling donor (MSD) and matched unrelated donor (MUD) HSCT to treat patients with agammaglobulinemia in the US., Design, Setting, and Participants: This economic evaluation used Markov analysis to model the base-case scenario of a patient aged 12 months with congenital agammaglobulinemia receiving lifelong IRT vs MSD or MUD HSCT. Costs, probabilities, and quality-of-life measures were derived from the literature. Microsimulations estimated premature deaths for each strategy in a virtual cohort. One-way sensitivity and probabilistic sensitivity analyses evaluated uncertainty around parameter estimates performed from a societal perspective over a 100-year time horizon. The threshold for cost-effective care was set at $100 000 per quality-adjusted life-year (QALY). This study was conducted from 2020 across a 100-year time horizon., Exposures: Immunoglobulin replacement therapy vs MSD or MUD HSCT for treatment of congenital agammaglobulinemia., Main Outcomes and Measures: The primary outcomes were incremental cost-effectiveness ratio (ICER) expressed in 2020 US dollars per QALY gained and premature deaths associated with each strategy., Results: In this economic evaluation of patients with congenital agammaglobulinemia, lifelong IRT cost more than HSCT ($1 512 946 compared with $563 776 [MSD] and $637 036 [MUD]) and generated similar QALYs (20.61 vs 17.25 [MSD] and 17.18 [MUD]). Choosing IRT over MSD or MUD HSCT yielded ICERs of $282 166 per QALY gained over MSD and $255 633 per QALY gained over MUD HSCT, exceeding the US willingness-to-pay threshold of $100 000/QALY. However, IRT prevented at least 2488 premature deaths per 10 000 microsimulations compared with HSCT. When annual IRT price was reduced from $60 145 to below $29 469, IRT became the cost-effective strategy. Findings remained robust in sensitivity and probabilistic sensitivity analyses., Conclusions and Relevance: In the US, IRT is more expensive than HSCT for agammaglobulinemia treatment. The findings of this study suggest that IRT prevents more premature deaths but does not substantially increase quality of life relative to HSCT. Reducing US IRT cost by 51% to a value similar to IRT prices in countries implementing value-based pricing may render it the more cost-effective strategy.