331 results on '"Khan DA"'
Search Results
2. Lead-induced oxidative stress adversely affects health of the occupational workers
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Khan, DA, primary, Qayyum, S, additional, Saleem, S, additional, and Khan, FA, additional
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- 2008
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3. Effectiveness of Helicobacter pylori eradication in chronic urticaria: evidence-based analysis using the Grading of Recommendations Assessment, Development, and Evaluation system.
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Shakouri A, Compalati E, Lang DM, and Khan DA
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- 2010
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4. Therapeutic alternatives for chronic urticaria: an evidence-based review, Part 2.
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Morgan M and Khan DA
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- 2008
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5. Therapeutic alternatives for chronic urticaria: an evidence-based review, part 1.
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Morgan M and Khan DA
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- 2008
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6. Bupropion in the treatment of outpatients with asthma and major depressive disorder.
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Brown ES, Vornik LA, Khan DA, and Rush AJ
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OBJECTIVE: Depressive disorders are common in asthma. Despite the high prevalence, antidepressant therapy in asthma patients with depression remains under-investigated. The objective of this pilot study was to investigate the use of bupropion for depression and anxiety in depressed asthma patients. METHOD: We conducted a 12-week open-label study of bupropion in 18 depressed asthma patients. Participants were assessed with the Hamilton Rating Scale for Depression (HAM-D-17), Hamilton Rating Scale for Anxiety (HAM-A), Inventory of Depressive Symptomatology--Self-Report (IDS-SR), Asthma Control Questionnaire (ACQ) and spirometry at baseline and weeks 1, 2, 4, 8, and 12. RESULTS: Significant baseline to exit improvements were observed on the HAM-D-17 (mean change = 4.72, SD = 7.78, p = 0.02) and the HAM-A (mean change = 2.12, SD = 3.97, p = 0.04). Based on the HAM-D-17 scores, 27.8% of the patients were responders and 16.7% were remitters. Significant correlations were found between changes in ACQ score and HAM-D-17 r = 0.73, p = 0.001), ACQ score and IDS-SR r = 0.58, = 0.012), and FEV1% Predicted and HAM-D-17 r = -0.66, p = 0.006). CONCLUSIONS: Bupropion treatment was associated with significant improvements in depression and anxiety symptoms in asthma patients. Improvements in asthma correlated significantly with improvements in depression. [ABSTRACT FROM AUTHOR]
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- 2007
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7. More therapeutic alternatives for chronic idiopathic urticaria?
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Zauli D, Tovoli F, DeGiorgi G, Morgan M, and Khan DA
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- 2008
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8. Spontaneous perforation of jejunal gastrintestinal stromal tumour (gist). Case report and review of literature
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Roy Somsubhra Datta, Khan Dawood, De Krishna K, and De Utpal
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Jejunum ,GIST ,Perforative peritonitis ,Surgery ,RD1-811 ,Medical emergencies. Critical care. Intensive care. First aid ,RC86-88.9 - Abstract
Abstract GIST is the commonest mesenchymal tumour of the gastrointestinal tract. Jejunal GIST is rare and spontaneous perforation of asymptomatic jejunal GIST is unique. A review of the English literature reveals only fifteen cases of perforated GIST till date. Pre-operative diagnosis is difficult. Diagnosis is confirmed on histopathology and immuno-histochemistry. Complete removal with postoperative imatinib therapy entails optimal treatment. Perforated GIST is associated with high recurrence.
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- 2012
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9. Early gene expression changes with rush immunotherapy
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Barnett Sherry, Bhutani Sumit, Davis Laurie S, and Khan David A
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Rush immunotherapy ,allergy ,gene expression ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Abstract Background To examine whether whole genome expression profiling could reveal changes in mRNA expression of peripheral blood mononuclear cells (PBMC) from allergic patients undergoing rush immunotherapy (RIT) that might be manifest within the first few months of treatment. Methods For this study, PBMC from three allergic patients undergoing RIT were assessed at four timepoints: prior to RIT, at 1 week and 7 week post-RIT, during build-up and at 4 months, after establishment of a maintenance dose. PBMC mRNA gene expression changes over time were determined by oligonucleotide microarrays using the Illumina Human-6 BeadChip Platform, which simultaneously interrogates expression profiles of > 47,000 transcripts. Differentially expressed genes were identified using well-established statistical analysis for microarrays. In addition, we analyzed peripheral blood basophil high-affinity IgE receptor (Fc epsilon RI) expression and T-regulatory cell frequency as detected by expression of CD3+CD4+CD25bright cells at each timepoint using flow cytometry. Results In comparing the initial 2 timepoints with the final 2 timepoints and analyzing for genes with ≥1.5-fold expression change (p less than or equal to 0.05, BH-FDR), we identified 507 transcripts. At a 2-fold change (p less than or equal to 0.05, BH-FDR), we found 44 transcripts. Of these, 28 were up-regulated and 16 were down-regulated genes. From these datasets, we have identified changes in immunologically relevant genes from both the innate and adaptive response with upregulation of expressed genes for molecules including IL-1β, IL-8, CD40L, BTK and BCL6. At the 4 month timepoint, we noted a downward trend in Fc epsilon RI expression in each of the three patients and increased allergen-specific IgG4 levels. No change was seen in the frequency of peripheral T-regulatory cells expressed over the four timepoints. Conclusions We observed significant changes in gene expression early in peripheral blood samples from allergic patients undergoing RIT. Moreover, serum levels for allergen specific IgG4 also increased over the course of treatment. These studies suggest that RIT induces rapid and dynamic alterations in both innate and adaptive immunity which can be observed in the periphery of allergic patients. These alterations could be directly related to the therapeutic shift in the allergen-specific class of immunoglobulin.
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- 2011
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10. Staged stromal extracellular 3D matrices differentially regulate breast cancer cell responses through PI3K and beta1-integrins
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Valianou Matthildi, Simons Jeffrey, Khan David R, Castelló-Cros Remedios, and Cukierman Edna
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Interactions between cancer cells and stroma are critical for growth and invasiveness of epithelial tumors. The biochemical mechanisms behind tumor-stromal interactions leading to increased invasiveness and metastasis are mostly unknown. The goal of this study was to analyze the direct effects of staged stroma-derived extracellular matrices on breast cancer cell behavior. Methods Early and late three-dimensional matrices were produced by NIH-3T3 and tumor-associated murine fibroblasts, respectively. After removing fibroblasts, extracted matrices were re-cultured with breast epithelial cells of assorted characteristics: MCF-10A (non-tumorigenic), MCF-7 (tumorigenic, non-invasive), and MDA-MB-231 (tumorigenic, invasive). Effects prompted by staged matrices on epithelial cell's growth, morphology and invasion were determined. Also, matrix-induced velocity, directionality and relative track orientation of invasive cells were assessed in the presence or absence of inhibitors of phosphoinositide-3 kinase (PI3K) and/or beta-1 integrin. Results We observed that assorted breast epithelial cells reacted differently to two-dimensional vs. staged, control (early) and tumor-associated (late), three-dimensional matrices. MCF-10A had a proliferative advantage on two-dimensional substrates while MCF-7 and MDA-MB-231 showed no difference. MCF-10A and MCF-7 formed morphologically distinguishable aggregates within three-dimensional matrices, while MDA-MB-231 exhibited increased spindle-shape morphologies and directional movements within three-dimensional matrices. Furthermore, MDA-MB-231 acquired a pattern of parallel oriented organization within tumor-associated, but not control matrices. Moreover, tumor-associated matrices induced PI3K and beta1-integrin dependent Akt/PKB activity in MDA-MB-231 cells. Interestingly, beta1-integrin (but not PI3K) regulated tumor-associated matrix-induced mesenchymal invasion which, when inhibited, resulted in a change of invasive strategy rather than impeding invasion altogether. Conclusion We propose that both cells and matrices are important to promote effective breast cancer cell invasion through three-dimensional matrices and that beta1-integrin inhibition is not necessarily sufficient to block tumor-matrix induced breast cancer cell invasion. Additionally, we believe that characterizing stroma staging (e.g., early vs. late or tumor-associated) might be beneficial for predicting matrix-induced cancer cell responses in order to facilitate the selection of therapies.
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- 2009
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11. Adverse reactions during drug challenges: a single US institution's experience.
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Kao L, Rajan J, Roy L, Kavosh E, and Khan DA
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- 2013
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12. Early gene expression changes with rush immunotherapy.
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Davis LS, Bhutani S, Barnett SR, and Khan DA
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- 2011
13. Psychiatric symptomatology and disorders in caregivers of children with asthma.
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Brown ES, Gan V, Jeffress J, Mullen-Gingrich K, Khan DA, Wood BL, Miller BD, Gruchalla R, and Rush AJ
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- 2006
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14. Approach to the diagnosis of drug hypersensitivity reactions: similarities and differences between Europe and North America
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Patrizia Bonadonna, Kimberly G. Blumenthal, María José Torres, Eric Macy, Annick Barbaud, Pascal Demoly, David A. Khan, Miguel A. Park, Antonino Romano, Gülfem Çelik, Mariana Castells, Werner Aberer, Cristobalina Mayorga, Allergy Unit [Malaga, Spain] (National Network ARADyAL), Hospital Regional Universitario de Málaga [Spain], The Andalusian Center for Nanomedicine and Biotechnology (BIONAND), Allergy Unit [Italy], Presidio Columbus [Italy]-Allergologia - Columbus - Policlinico Gemelli [Italy], Istituto di Ricovero e Cura a Carattere Scientifico [Troina, Italy] (IRCCS), Oasi Maria Santissima Srl [Troina, Italy], Department of Chest Diseases [Ankara, Turkey], Division of Immunology and Allergy [Ankara, Turkey], Ankara University School of Medicine [Turkey]-Ankara University School of Medicine [Turkey], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Department of Internal Medicine [Dallas, TX, USA], University of Texas Southwestern Medical Center [Dallas], Kaiser Permanente, Division of Allergic Diseases [Rochester, MN, USA], Mayo Clinic [Rochester], Division of Rheumatology, Allergy and Immunology [Boston, MA, USA] (Department of Medicine), Massachusetts General Hospital [Boston], Department of Dermatology [Graz, Austria], Medical University Graz, Division of Rheumatology, Immunology and Allergy [Boston, MSA, USA], Brigham and Women's Hospital [Boston], Service de dermatologie et allergologie [CHU Tenon], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Sorbonne Paris Cité (USPC), Allergy Unit [Verona, Italy], Azienda ospedaliera universitaria integrata di Verona [Italy], [Torres,MJ, Mayorga,] Allergy Unit, National Network ARADyAL, IBIMA-Regional University Hospital of Malaga-UMA, Malaga, Spain. [Torres,MJ] BIONAND-Andalusian Centre for Nanomedicine and Biotechnology, Malaga, Spain. [Romano,A] Allergy Unit, Presidio Columbus, Rome, Italy. IRCCS Oasi Maria S.S., Troina, Italy. [Celik,G] Department of Chest Diseases, Division of Immunology and Allergy, Ankara University School of Medicine, Ankara, Turkey. [Demoly,P] Hôpital Arnaud de Villeneuve, University Hospital of Montpellier and Sorbonne Universités, UPMC Paris , IPLESP, Equipe EPAR, Paris, France. [Khan,DA] Department of Internal Medicine, Division of Allergy and Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA. [Macy,E] Kaiser Permanente Health Care Program, San Diego, CA, USA. [Park,M] Mayo Clinic College of Medicine, Division of Allergic Diseases, Mayo Clinic, Rochester, MN , USA. [Blumenthal,K] Division of Rheumatology, Allergy and Immunology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. [Aberer,W] Department of Dermatology, Medical University of Graz, Graz, Austria. [Castells,M] Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital, Boston, MSA, USA. [Barbaud,A] Sorbonne Universities, UPMC Univ Paris, Dermatology and Allergology Department, Tenon Hospital (AP-HP), Paris, France. [Allergy Unit, IBIMA-Regional University Hospital of Malaga-UMA (Pavilion C) Malaga, Spain. [Bonadonna,P] Allergy Unit, Azienda Ospedaliera Universitaria Intergrata of Verona, Verona, Italy., BMC, BMC, Hospital Regional Universitario de Málaga = Regional University Hospital of Malaga [Spain], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)
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0301 basic medicine ,Allergy ,[SDV]Life Sciences [q-bio] ,Provocation test ,Presumptive diagnosis ,Review ,Anafilaxia ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,0302 clinical medicine ,Health Care::Population Characteristics::Demography::Ethnic Groups [Medical Subject Headings] ,Clinical history ,Salud pública ,Diagnosis ,Immunology and Allergy ,media_common ,education.field_of_study ,Geographical Locations::Geographic Locations::Americas::North America::United States [Medical Subject Headings] ,Estados Unidos ,Health Care::Population Characteristics::Health::Public Health [Medical Subject Headings] ,3. Good health ,Humanos ,[SDV] Life Sciences [q-bio] ,Europe ,Diseases::Chemically-Induced Disorders::Drug-Related Side Effects and Adverse Reactions::Drug Hypersensitivity [Medical Subject Headings] ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Evaluation Studies as Topic::Drug Evaluation [Medical Subject Headings] ,Pruebas cutáneas ,IgE ,Drug ,Hipersensibilidad a las drogas ,Europa ,Evaluación de Medicamentos ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,In vitro test ,media_common.quotation_subject ,Concordance ,Immunology ,Population ,Sensitization ,03 medical and health sciences ,Skin test ,medicine ,Hypersensitivity ,Intensive care medicine ,education ,business.industry ,Public health ,T-cells ,Diseases::Immune System Diseases::Hypersensitivity::Hypersensitivity, Immediate::Anaphylaxis [Medical Subject Headings] ,medicine.disease ,United States ,Surgery ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Immunologic Tests::Skin Tests [Medical Subject Headings] ,Grupos étnicos ,030104 developmental biology ,030228 respiratory system ,Drug provocation test ,Geographical Locations::Geographic Locations::Europe [Medical Subject Headings] ,business ,Unit States - Abstract
International audience; AbstractDrug hypersensitivity reactions (DHRs) affect an unknown proportion of the general population, and are an important public health problem due to their potential to cause life-threatening anaphylaxis and rare severe cutaneous allergic reactions. DHR evaluations are frequently needed in both ambulatory and hospital settings and have a complex diagnosis that requires a detailed clinical history and other tests that may include in vitro tests and in vivo procedures such as skin tests and drug provocation tests. Although over the years both European and U.S. experts have published statements on general procedures for evaluating DHRs, a substantial discordance in their daily management exists. In this review, we highlight both the differences and the similarities between the European and U.S. perspectives. While a general consensus exists on the importance of skin tests for evaluating DHRs, concordance between Americans and Europeans exists solely regarding their use in immediate reactions and the fact that a confirmation of a presumptive diagnosis by drug provocation tests is often the only reliable way to establish a diagnosis. Finally, great heterogeneity exists in the application of in vitro tests, which require further study to be well validated.
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- 2016
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15. Depressive symptom severity in mid- to late life in individuals with and without asthma.
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Palka JM, Peacock M, Tusken M, Ibrahim M, Najjab A, Carter L, Khan DA, and Brown ES
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- 2024
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16. Corrigendum to <'A systematic review and expert Delphi Consensus recommendation on the use of vaccines in patients receiving dupilumab: A position paper of the American College of Allergy, Asthma and Immunology'> <[Annals of Allergy, Asthma & Immunology 133 (2024) 286-94]>.
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Lieberman JA, Chu DK, Ahmed T, Dribin TE, Abrams EM, Anagnostou A, Blumenthal KG, Boguniewicz M, Chase NM, Golden DBK, Hartog NL, Heimall JR, Ho T, Lawrence MG, Khan DA, Minniear TD, Mustafa SS, Oppenheimer JJ, Phillips EJ, Ramsey A, Rider NL, Schneider L, Shaker MS, Spergel JM, Stone CA Jr, Stukus DR, Wang J, and Greenhawt MJ
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- 2024
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17. Health disparities in the Middle East: Representative analysis of the region.
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Assa'ad A, Hershko AY, Irani C, Mahdavinia M, Khan DA, and Bernstein JA
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Health care disparities refer to differences in health and health care between groups that are closely associated with governmental, social, economic, and/or environmental policies. To address this gap in knowledge, a forum to address health disparities in different regions of the world was developed as an American Academy of Allergy, Asthma & Immunology (AAAAI) presidential initiative (under Dr Jonathan Bernstein) in partnership with the World Allergy Organization to better understand political and socioeconomic issues within different countries and how they affect their health care systems. The first region selected was the Middle East. Representatives from Egypt, Israel, Lebanon, and Iran were invited to speak at this forum. Although we were not able to be inclusive of all countries in this region, it is apparent that the health care systems for those that participated are heterogeneous as a result of socioeconomic, educational, and governmental infrastructures. However, all regions noted health disparities that appeared to be linked to social determinants of health. Unfortunately, conflict in this region has had an additional adverse effect on these health care systems, making solutions even more challenging. However, recognition of the problems that loom large for allergy/immunology in particular can provide an opportunity for international collaboration that focuses on providing patient and physician education and identifying strategies to improve access to specialized health care., Competing Interests: Supported by the AAAAI and WAO. Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest., (© 2024 The Author(s).)
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- 2024
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18. Disparities in hereditary angioedema in an urban medical district.
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Trickett JS, Khan DA, and Chambliss JM
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- 2024
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19. Patient-Reported Outcome Measures in Food and Drug Allergy.
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Anagnostou A, Warren C, Dantzer J, Galvin AD, Phillips EJ, Khan DA, and Banerji A
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- Humans, Surveys and Questionnaires, Patient Reported Outcome Measures, Food Hypersensitivity diagnosis, Quality of Life, Drug Hypersensitivity diagnosis
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A patient-reported outcome is directly reported by the patient without interpretation of the patient's response by anyone else. It refers to the patient's health (symptoms and feelings), quality of life, or functional status associated with health care or treatment. Patient-reported outcome measures (PROMs) are defined as the tools or instruments that are used to measure patient-reported outcomes. Health-related quality of life has been the most studied psychosocial PROM in food allergy, using validated questionnaires. In drug allergy, PROMs are useful in capturing patients' experiences of potential allergic reactions, including subjective symptoms such as headache, dizziness, or fatigue. Patient-reported outcome measures can also help differentiate true allergies from side effects or other nonallergic reactions and inform decisions about drug challenges and de-labeling strategies. Ensuring the chosen tool is validated for the specific allergy context is crucial for accurate data collection. Integrating patient-reported experiences alongside traditional methods can lead to more accurate assessments and personalized care., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
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- 2024
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20. Cephalosporin Allergy: Updates on Diagnostic Testing.
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Chow TG, Brunner ES, and Khan DA
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- Humans, Cross Reactions immunology, Diagnostic Tests, Routine, Cephalosporins adverse effects, Cephalosporins immunology, Drug Hypersensitivity diagnosis, Drug Hypersensitivity immunology, Skin Tests, Anti-Bacterial Agents adverse effects, Anti-Bacterial Agents immunology
- Abstract
Purpose of Review: Cephalosporins are one of the most prescribed antibiotics worldwide and are implicated in a wide range of hypersensitivity reactions (HSR). This review summarizes recent updates in cephalosporin hypersensitivity with a focus on diagnostic testing., Recent Findings: Reported testing strategies to evaluate different immediate and delayed cephalosporin HSR have included skin testing, in vitro testing, and diagnostic drug challenges. However, the diagnostic performance of in vivo and in vitro tests remains unclear across different hypersensitivity endotypes; adequately powered studies investigating the true positive and negative predictive value of these diagnostic modalities are needed using the reference standard of drug challenges to define cephalosporin hypersensitivity. Refinement of diagnostic testing should be guided by growth in our understanding of cephalosporin antigenic determinants. This growth will be crucial in driving further clarification of cross-reactivity between cephalosporins, and potentially delineating streamlined evaluation processes resulting in reduced unnecessary antibiotic avoidance., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2024
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21. Leukotriene receptor antagonists as add-on therapy to antihistamines for urticaria: Systematic review and meta-analysis of randomized clinical trials.
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Rayner DG, Liu M, Chu AWL, Chu X, Guyatt GH, Oykhman P, Cao DJ, Moellman J, Ben-Shoshan M, Baker DR, Waserman S, Lang D, Sheikh J, Mathur SK, Beck LA, Khan DA, Oliver ET, Asiniwasis RN, Cole EF, Wheeler KE, Runyon L, Chan J, Trayes KP, Eftekhari S, Gardner DD, Winders T, Saini SS, Bernstein JA, and Chu DK
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- Humans, Drug Therapy, Combination, Histamine Antagonists therapeutic use, Histamine H1 Antagonists therapeutic use, Quality of Life, Randomized Controlled Trials as Topic, Leukotriene Antagonists therapeutic use, Urticaria drug therapy
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Background: The benefits and harms of adding antileukotrienes to H
1 antihistamines (AHs) for the management of urticaria (hives, itch, and/or angioedema) remain unclear., Objective: We sought to systematically synthesize the treatment outcomes of antileukotrienes in combination with AHs versus AHs alone for acute and chronic urticaria., Methods: As part of updating American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters urticaria guidelines, we searched Medline, Embase, Central, LILACS, WPRIM, IBECS, ICTRP, CBM, CNKI, VIP, Wanfang, US Food and Drug Administration, and European Medicines Agency databases from inception to December 18, 2023, for randomized controlled trials (RCTs) evaluating antileukotrienes and AHs versus AHs alone in patients with urticaria. Paired reviewers independently screened citations, extracted data, and assessed risk of bias. Random effects models pooled effect estimates for urticaria activity, itch, wheal, sleep, quality of life, and harms. The GRADE approach informed certainty of evidence ratings. The study was registered at the Open Science Framework (osf.io/h2bfx/)., Results: Thirty-four RCTs enrolled 3324 children and adults. Compared to AHs alone, the combination of a leukotriene receptor antagonist with AHs probably modestly reduces urticaria activity (mean difference, -5.04; 95% confidence interval, -6.36 to -3.71; 7-day urticaria activity score) with moderate certainty. We made similar findings for itch and wheal severity as well as quality of life. Adverse events were probably not different between groups (moderate certainty); however, no RCT reported on neuropsychiatric adverse events., Conclusion: Among patients with urticaria, adding leukotriene receptor antagonists to AHs probably modestly improves urticaria activity with little to no increase in overall adverse events. The added risk of neuropsychiatric adverse events in this population with leukotriene receptor antagonists is small and uncertain., Competing Interests: Disclosure statement This work was commissioned and funded by the American Academy of Allergy, Asthma & Immunology (AAAAI) and the American College of Allergy, Asthma & Immunology (ACAAI) through the Joint Task Force on Practice Parameters to inform upcoming guidance on the management of CU. The task force contributed to defining the scope of the review but otherwise had no role in study design, data collection, data analysis, or data interpretation. The funder received a copy of the report before submission. The review team had the ability, but not the obligation, to consider the funders’ feedback. Disclosure of potential conflict of interest: M. Ben-Shoshan reports consulting fees from Sanofi/Regeneron and Novartis. S. Waserman reports consulting fees from Medexus Pharmaceuticals and Miravo Healthcare. S. K. Mathur reports consulting fees from Novartis. E. T. Oliver reports consulting fees from Novartis and Sanofi/Regeneron. R. N. Asiniwasis reports payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from Medexus Pharmaceuticals. S. Eftekhari is employed by the Asthma and Allergy Foundation of America, a nonprofit patient organization, which has received grants for patient education and unbranded initiatives from AstraZeneca, Bayer, Johnson & Johnson, Merck, and Sanofi/Regeneron. T. Winders reports payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from AstraZeneca, GlaxoSmithKline, Merek, Novartis, and Sanofi/Regeneron. J. Bernstein reports consulting fees from AstraZeneca, Merck, Sanofi/Regeneron, and Pfizer; and leadership role in the AAAAI and the US Hereditary Angioedema Association. The rest of the authors declare that they have no relevant conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2024
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22. Topical corticosteroids for hives and itch (urticaria): Systematic review and Bayesian meta-analysis of randomized trials.
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Chu AWL, Rayner DG, Chu X, Chen L, Dong AYH, Waserman S, Baker DR, Sheikh J, Moellman J, Lang DM, Ben-Shoshan M, Mathur SK, Beck LA, Khan DA, Oliver ET, Asiniwasis RN, Chan J, Cole EF, Trayes KP, Frazier WT, Runyon L, Wheeler KE, Eftekhari S, Gardner DD, Winders T, Bernstein JA, Saini SS, and Chu DK
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- Adult, Humans, Administration, Topical, Bayes Theorem, Randomized Controlled Trials as Topic, Young Adult, Pruritus diagnosis, Pruritus drug therapy, Urticaria diagnosis, Urticaria drug therapy, Glucocorticoids administration & dosage, Glucocorticoids adverse effects
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Background: Topical corticosteroids are widely used as a treatment for itch and wheals (urticaria), but their benefits and harms are unclear., Objective: To systematically synthesize the benefits and harms of topical corticosteroids for the treatment of urticaria., Methods: We searched MEDLINE, EMBASE, and CENTRAL from database inception to March 23, 2024, for randomized trials comparing topical corticosteroids with placebo for patients with urticaria (either chronic spontaneous or inducible urticaria or acute urticaria elicited from skin/intradermal allergy testing). Paired reviewers independently screened records, extracted data, and assessed risk of bias. Random-effects meta-analyses addressed urticaria severity, itch severity (numeric rating scale; range 0-10; higher is worse), and adverse events. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach informed certainty of evidence ratings. PROSPERO registration: CRD42023455182., Results: A total of 19 randomized controlled trials enrolled 379 participants with a median of mean age of 30.1 (range 21.1-44.0) years. Compared with placebo, topical corticosteroids may reduce wheal size (ratio of means 0.47, 95% CI 0.38-0.59; low certainty) and itch severity (mean difference -1.30, 95% CI -5.07 to 2.46; very low certainty). Topical corticosteroids result in little to no difference in overall adverse events (94 fewer patients per 1000, 95% credible intervals 172 fewer to 12 more; high certainty)., Conclusion: Compared with placebo, topical corticosteroids may result in a reduction of wheal size and little to no difference in overall adverse events. Topical corticosteroids may reduce itch severity, but the evidence is very uncertain. Future large, randomized trials addressing the use of topical corticosteroids would further support optimal urticaria management., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2024
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23. The relationship between asthma and suggested alcohol dependence and heavy alcohol use in the Cooper Center Longitudinal Study: The role of depressive symptom severity.
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Agarwal CD, Shuval K, Li Q, DeFina LF, Barlow CE, Khan DA, and Brown ES
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- Humans, Male, Female, Longitudinal Studies, Adult, Middle Aged, Severity of Illness Index, Surveys and Questionnaires, Comorbidity, Logistic Models, Aged, Asthma epidemiology, Asthma psychology, Alcoholism epidemiology, Alcoholism psychology, Alcohol Drinking epidemiology, Alcohol Drinking psychology, Depression epidemiology, Depression psychology
- Abstract
Background: Asthma appears to be associated with a variety of psychiatric illnesses including depression and alcohol use disorder. The current study examined the relationship between asthma, heavy alcohol intake and suggested alcohol dependence controlling for depressive symptom severity., Methods: Data from 37,625 adult patients at the Cooper Clinic who enrolled in the Cooper Center Longitudinal Study, completed a medical history questionnaire including information on asthma, depressive symptoms and alcohol use were used. The association between lifetime asthma and heavy alcohol intake, while accounting for depressive symptoms (10-item Center for Epidemiological Studies-Depression (CESD)), and demographic variables was examined employing logistic regression with heavy alcohol intake (yes/no) as the outcome. Logistic regression was similarly utilized to examine the association between asthma and suggested alcohol dependence (CAGE scores ≥2: yes/no) among current drinkers (n = 29,235)., Results: Multivariable analysis revealed no significant association between asthma and heavy alcohol consumption with or without controlling for CES-D scores. Asthma was, however, associated with higher odds for suggested alcohol dependence (OR 1.18, 95 % CI 1.07, 1.31), which was attenuated but still significant when controlling for CES-D scores., Conclusion: Asthma was associated with higher risk for suggested alcohol dependence while current heaving drinking risk was not increased. The suggested drinking findings were slightly less strong when controlling for CES-D scores. The differences between current heavy drinking and CAGE findings might be due to differences in perception of problematic drinking by people with asthma or the timeframe of the assessments (current for drinking, lifetime for CAGE)., Competing Interests: Declaration of competing interest Dr. Brown has been on advisory boards for Sage/Biogen and Medscape/WebMD in the past three years on topics unrelated to the topic of the current paper. The other authors report no potential conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2025
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24. AI-CADR: Artificial Intelligence Based Risk Stratification of Coronary Artery Disease using Novel Non-invasive Biomarkers.
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Sajid M, Hassan A, Khan DA, Khan SA, Bakhshi AD, Akram MU, Babar M, Hussain F, and Abdul W
- Abstract
Coronary artery disease (CAD) is one of the most common causes of sudden cardiac arrest, accounting for a large percentage of global mortality. A timely diagnosis and detection may save a person's life. The research suggests a methodological framework for non-invasive risk stratification based on information only possible after invasive coronary angiography. Novel clinical, chemical, and molecular cardiac biomarkers were used as input features from an especially collected dataset. Following a thorough evaluative search in the biomarker feature space, the optimum feature and classifier or regression technique (regressor) set were selected using K-fold cross-validation. Ten machine learning (ML) classifiers were employed in classification tasks to determine the number of affected cardiac vessels, the Gensini group, and the severity of CAD with 82.58%, 86.26%, and 90.91% accuracy, respectively. Eleven approaches were used in regression tasks to calculate stenosis percentage and Gensini score, with R-squared values of 0.58 and 0.56, respectively. Following a thorough evaluative search in the biomarkers feature space, the optimum feature and classifier or regressor set were selected using K-fold cross-validation. The biomarkers and classifier or regressor combinations serve as the foundation for the proposed risk stratification framework, incorporating clinical protocol. Finally, our proposed framework is compared to state-of-the-art studies, offering a robust, well-rounded, early detection capable, and novel 'biomarkers-ML combination' approach to risk stratification.
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- 2024
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25. A systematic review and expert Delphi Consensus recommendation on the use of vaccines in patients receiving dupilumab: A position paper of the American College of Allergy, Asthma and Immunology.
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Lieberman JA, Chu DK, Ahmed T, Dribin TE, Abrams EM, Anagnostou A, Blumenthal KG, Boguniewicz M, Chase NM, Golden DBK, Hartog NL, Heimall JR, Ho T, Lawrence MG, Khan DA, Minniear TD, Mustafa SS, Oppenheimer JJ, Phillips EJ, Ramsey A, Rider NL, Schneider L, Shaker MS, Spergel JM, Stone CA Jr, Stukus DR, Wang J, and Greenhawt MJ
- Subjects
- Humans, Asthma drug therapy, Consensus, Delphi Technique, Dermatitis, Atopic drug therapy, Vaccination adverse effects, Antibodies, Monoclonal, Humanized therapeutic use, Vaccines adverse effects, Vaccines therapeutic use
- Abstract
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.)
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- 2024
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26. A comprehensive identification of potential molecular targets and small drugs candidate for melanoma cancer using bioinformatics and network-based screening approach.
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Khan DA, Adhikary T, Sultana MT, and Toukir IA
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- Humans, Antineoplastic Agents pharmacology, Gene Expression Profiling, Molecular Dynamics Simulation, Molecular Targeted Therapy, Small Molecule Libraries pharmacology, Small Molecule Libraries chemistry, MicroRNAs genetics, Melanoma genetics, Melanoma drug therapy, Melanoma metabolism, Computational Biology methods, Gene Regulatory Networks, Molecular Docking Simulation, Protein Interaction Maps drug effects, Gene Expression Regulation, Neoplastic drug effects
- Abstract
Melanoma is the third most common malignant skin tumor and has increased in morbidity and mortality over the previous decade due to its rapid spread into the bloodstream or lymphatic system. This study used integrated bioinformatics and network-based methodologies to reliably identify molecular targets and small molecular medicines that may be more successful for Melanoma diagnosis, prognosis and treatment. The statistical LIMMA approach utilized for bioinformatics analysis in this study found 246 common differentially expressed genes (cDEGs) between case and control samples from two microarray gene-expression datasets (GSE130244 and GSE15605). Protein-protein interaction network study revealed 15 cDEGs (PTK2, STAT1, PNO1, CXCR4, WASL, FN1, RUNX2, SOCS3, ITGA4, GNG2, CDK6, BRAF, AGO2, GTF2H1 and AR) to be critical in the development of melanoma (KGs). According to regulatory network analysis, the most important transcriptional and post-transcriptional regulators of DEGs and hub-DEGs are ten transcription factors and three miRNAs. We discovered the pathogenetic mechanisms of MC by studying DEGs' biological processes, molecular function, cellular components and KEGG pathways. We used molecular docking and dynamics modeling to select the four most expressed genes responsible for melanoma malignancy to identify therapeutic candidates. Then, utilizing the Connectivity Map (CMap) database, we analyzed the top 4-hub-DEGs-guided repurposable drugs. We validated four melanoma cancer drugs (Fisetin, Epicatechin Gallate, 1237586-97-8 and PF 431396) using molecular dynamics simulation with their target proteins. As a result, the results of this study may provide resources to researchers and medical professionals for the wet-lab validation of MC diagnosis, prognosis and treatments.Communicated by Ramaswamy H. Sarma.
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- 2024
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27. Contribution of caregiver and child anxiety and depressive symptoms to child asthma-related quality of life.
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Gwak DY, Tea JC, Fatima FN, Palka JM, Lehman H, Khan DA, Zhou H, Wood BL, Miller BD, and Brown ES
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- Humans, Child, Male, Female, Adolescent, Cross-Sectional Studies, Surveys and Questionnaires, Quality of Life psychology, Asthma psychology, Asthma epidemiology, Caregivers psychology, Anxiety psychology, Anxiety epidemiology, Depression epidemiology, Depression psychology
- Abstract
Background: Depression and anxiety negatively affect asthma-related quality of life (QoL). Yet, little is known regarding mood and asthma-related factors that best uniquely explain asthma-related QoL in children., Objective: This cross-sectional study evaluated the unique variance explained by caregiver and child depressive and anxiety symptom severity in child asthma-related QoL, apart from that explained by demographics and asthma control., Methods: Children aged 7 to 17 years with asthma (n = 205) and their caregivers with major depressive disorder were included. A 3-stage hierarchical linear regression analysis was conducted with the Pediatric Asthma Quality of Life Questionnaire total scores considered as the outcome. Predictors included demographic characteristics (stage 1); asthma control assessed by the Asthma Control Test (stage 2); and caregiver depression and anxiety (Hamilton Rating Scale for Depression and the Spielberger State/Trait Anxiety Scale) and child depression and anxiety (Children's Depression Inventory and the Screen for Child Anxiety-Related Disorders) (stage 3)., Results: Demographic characteristics accounted for only 5.5% of the Pediatric Asthma Quality of Life Questionnaire scores. Asthma control significantly increased variance explained in QoL to 32.6%, whereas caregiver and child depression and anxiety symptoms significantly increased variance explained to 42.6%. Child anxiety was found to uniquely explain the largest proportion of variance in QoL (r
s 2 = 0.584)., Conclusion: After adjusting variance in QoL for demographic characteristics and asthma control, caregiver and child depression and anxiety measures significantly increased the proportion of variance explained in a child's asthma-related QoL. In addition to better asthma control, child and caregiver depression and anxiety should be addressed to increase child asthma-related QoL., Trial Registration: ClinicalTrials.gov Identifier: NCT02809677., Competing Interests: Disclosures Dr Brown reports serving on an advisory board for Medscape/WebMD. The other authors have no conflicts of interest to report., (Copyright © 2024 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)- Published
- 2024
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28. Postoperative complications among dialysis-requiring patients undergoing splenectomy.
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Waqar U, Mudabbir RMA, Angez M, Ahmed KS, Khan DA, Arshad MS, and Zafar H
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- Humans, Female, Male, Middle Aged, Retrospective Studies, Aged, Adult, Kidney Failure, Chronic therapy, Kidney Failure, Chronic complications, Length of Stay, Splenectomy adverse effects, Postoperative Complications epidemiology, Postoperative Complications etiology, Postoperative Complications mortality, Renal Dialysis
- Abstract
Background: Dialysis patients are at high risk for surgery, but their outcomes after splenectomy are unclear. We compared postoperative complications between dialysis and non-dialysis patients., Methods: Data were retrieved from the National Surgical Quality Improvement Program for this retrospective cohort. Adult patients undergoing elective splenectomy between 2005 and 2020 were included., Results: Among 10,339 included patients, 143(1.4%) were on chronic dialysis. Postoperative mortality was higher in dialysis vs. non-dialysis patients (9.1% vs. 1.8%). Dialysis patients were more likely to have 30-day major morbidity, infectious and non-infectious complications, reoperation, and prolonged hospital stay. On multivariable regression, dialysis dependence significantly increased odds of mortality, major morbidity, blood transfusion, prolonged length of stay, reoperation, and failure-to-rescue (FTR)., Conclusion: Dialysis patients were at higher risk of postoperative morbidity following splenectomy. Additionally, the risk of FTR in this patient population is also significantly more compared to non-dialysis patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2024
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29. Chronic Spontaneous Urticaria: An Update on the Evaluation and Management.
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Joshi SR, Anstey KM, and Khan DA
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- Humans, Disease Management, Omalizumab therapeutic use, Biomarkers, Histamine Antagonists therapeutic use, Anti-Allergic Agents therapeutic use, Immunoglobulin E immunology, Immunosuppressive Agents therapeutic use, Chronic Urticaria diagnosis, Chronic Urticaria therapy, Chronic Urticaria drug therapy
- Abstract
Chronic spontaneous urticaria (CSU) affects 0.5% to 1% of the general population and is often managed by allergy and immunology specialists. Guidelines have evolved over the past several decades with an emphasis on decreasing extensive screening laboratory testing as they are of low-yield and cost-ineffective. The utility of biomarkers remains under investigation but total immunoglobulin E may be helpful in determining specific endotypes and response to omalizumab. Antihistamines and omalizumab remain the primary therapeutic options for CSU, but an expanding body of evidence supports the use of immunosuppressants and anti-inflammatory medications in refractory cases., Competing Interests: Disclosure The authors declare the following competing financial interest(s): S.R. Joshi was a paid advisor for Novartis, Sanofi, Genentech, and Regeneron. K.M. Anstey and D. Khan have no financial interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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30. Factors Affecting 30-Day Outcomes in Patients Undergoing Nontraumatic Upper Extremity Amputation: A Retrospective Descriptive Longitudinal Study.
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Ahmed W, Fatimi AS, Hamza M, Waqar U, Khan DA, Rauf H, Jivani N, and Noordin S
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- Humans, Retrospective Studies, Male, Female, Middle Aged, Aged, Risk Factors, Longitudinal Studies, Postoperative Complications epidemiology, Treatment Outcome, Adult, Amputation, Surgical, Upper Extremity surgery
- Abstract
Background: Current literature concerning upper extremity amputations (UEAs) is very sparse. In this study, we conducted the first multicenter retrospective analysis aiming to identify risk factors associated with unfavorable outcomes in patients undergoing nontraumatic UEAs., Methods: A retrospective cohort study was conducted using the National Surgical Quality Improvement Program database. Adult patients who underwent nontraumatic UEAs between 2005 and 2021 were divided into two cohorts based on whether they experienced 30-day major morbidity (MM). Thereafter, multivariable binary logistic regression analysis was used to identify risk factors of MM., Results: From a total of 2984 cases, MM was observed in 8.7% of patients. Factors associated with MM included American Society of Anesthesiologists classes 3 (odds ratio [OR], 2.974 [1.862 to 4.748]) and 4 (OR, 4.736 [2.857 to 7.848]), being underweight (OR, 2.370 [1.251 to 4.491]), and suffering from insulin-dependent diabetes (OR, 1.390 [1.018 to 1.898]). In addition, an infectious surgical indication was associated with an increased risk of MM compared with having a benign (OR, 0.648 [0.488 to 0.682]) or malignant (OR, 0.205 [0.091 to 0.462]) indication. Moreover, patients undergoing shoulder amputations were at an increased risk of MM compared with those undergoing amputations of the forearm/wrist (OR, 0.243 [0.072 to 0.819]) and hands/fingers (OR, 0.286 [0.095 to 0.861])., Conclusion: The risk factors identified for MM after nontraumatic UEAs should guide surgeons toward appropriately identifying high-risk patients and adequately counseling them preoperatively., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons.)
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- 2024
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31. The Impact of Prior Authorization on Clinical Practice and Patient Care Outcomes: A Work Group Report of the AAAAI Prior Authorization Task Force.
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Bernstein JA, Gadde D, Yassin M, Abramson SL, Bansal P, Joshi SR, Kabbash LG, Soong W, West JB, and Khan DA
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- Humans, Surveys and Questionnaires, United States, Practice Patterns, Physicians' statistics & numerical data, Patient Care, Prior Authorization, Advisory Committees, Allergy and Immunology
- Abstract
The Prior Authorization Task Force of the American Academy of Allergy, Asthma & Immunology (AAAAI), a presidential initiative of David Khan, MD, FAAAI, was established to develop an AAAAI position statement outlining ways to improve health care for our patients, to support legislation that advocates for prior authorization (PA) reform and identify the impact PA has on its membership using a questionnaire survey. This article describes the results of this survey. An electronic anonymous survey questionnaire was developed to assess the impact and burden of PA on AAAAI members and their staff and patients. Surveys were sent to randomly selected members and fellows of the AAAAI in the United States. Descriptive statistics were used to analyze the results by the Information Services team of the AAAAI and the authors of this work group report. The questionnaire responses from allergy immunology specialists demographically reflected the AAAAI membership and indicate that PAs can significantly affect patient care delivery and increase administrative burden to clinical practices, leading to serious adverse events in some circumstances. Differential responses regarding PAs for various medication classes likely reflect the physician's patient population, which can shift prescribing patterns. Prior authorization is a serious health care problem that is wasting financial resources and needlessly placing patients in danger when they are unable to access medications or medical services required for clinical management. The results of this questionnaire study support the recommendations made in the recent AAAAI position statement on PA., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
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- 2024
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32. Efficacy and Safety of Systemic Corticosteroids for Urticaria: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.
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Chu X, Wang J, Ologundudu L, Brignardello-Petersen R, Guyatt GH, Oykhman P, Bernstein JA, Saini SS, Beck LA, Waserman S, Moellman J, Khan DA, Ben-Shoshan M, Baker DR, Oliver ET, Sheikh J, Lang D, Mathur SK, Winders T, Eftekhari S, Gardner DD, Runyon L, Asiniwasis RN, Cole EF, Chan J, Wheeler KE, Trayes KP, Tran P, and Chu DK
- Subjects
- Humans, Treatment Outcome, Histamine Antagonists therapeutic use, Chronic Urticaria drug therapy, Drug Therapy, Combination, Randomized Controlled Trials as Topic, Adrenal Cortex Hormones therapeutic use, Urticaria drug therapy
- Abstract
Background: Short courses of adjunctive systemic corticosteroids are commonly used to treat acute urticaria and chronic urticaria flares (both with and without mast cell-mediated angioedema), but their benefits and harms are unclear., Objective: To evaluate the efficacy and safety of treating acute urticaria or chronic urticaria flares with versus without systemic corticosteroids., Methods: We searched the MEDLINE, EMBASE, CENTRAL, CNKI, VIP, Wanfang, and CBM databases from inception to July 8, 2023, for randomized controlled trials of treating urticaria with versus without systemic corticosteroids. Paired reviewers independently screened records, extracted data, and appraised risk of bias with the Cochrane 2.0 tool. We performed random-effects meta-analyses of urticaria activity, itch severity, and adverse events. We assessed certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluations (GRADE) approach., Results: We identified 12 randomized trials enrolling 944 patients. For patients with low or moderate probability (17.5%-64%) to improve with antihistamines alone, add-on systemic corticosteroids likely improve urticaria activity by a 14% to 15% absolute difference (odds ratio [OR], 2.17, 95% confidence interval [CI]: 1.43-3.31; number needed to treat [NNT], 7; moderate certainty). Among patients with a high chance (95.8%) for urticaria to improve with antihistamines alone, add-on systemic corticosteroids likely improved urticaria activity by a 2.2% absolute difference (NNT, 45; moderate certainty). Corticosteroids may improve itch severity (OR, 2.44; 95% CI: 0.87-6.83; risk difference, 9%; NNT, 11; low certainty). Systemic corticosteroids also likely increase adverse events (OR, 2.76; 95% CI: 1.00-7.62; risk difference, 15%; number needed to harm, 9; moderate certainty)., Conclusions: Systemic corticosteroids for acute urticaria or chronic urticaria exacerbations likely improve urticaria, depending on antihistamine responsiveness, but also likely increase adverse effects in approximately 15% more., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2024
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33. Comparative efficacy of tocotrienol and tocopherol (vitamin E) on atherosclerotic cardiovascular diseases in humans.
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Rafique S, Khan DA, Farhat K, Khan MA, Noor M, and Sharif M
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- Humans, Cardiovascular Diseases prevention & control, Dyslipidemias drug therapy, Cholesterol blood, Tocotrienols therapeutic use, Tocotrienols pharmacology, Atherosclerosis drug therapy, Atherosclerosis prevention & control, Tocopherols therapeutic use, Antioxidants therapeutic use
- Abstract
Objective: To compare the efficacy of tocotrienol and tocopherol in the management of patients with atherosclerotic cardiovascular diseases., Methods: The systematic review was conducted in line with Preferred Reporting Items for Systematic Reviews and Meta- Analyses guidelines 2020, and comprised literature search from 2002 till January 5, 2023, on PubMed, Google Scholar, Cochrane Library, Google, Wiley-Inter Science Library, Medline, SpringerLink, Taylor and Francis databases. The search was conducted using key words, such as: "tocopherol", "tocotrienol", "vitamin E", "dyslipidaemia", "cardiovascular diseases" "cardioprotective", "hypercholesterolemia" and "atherosclerosis" along with Boolean operators. Human clinical studies regarding the use of tocotrienol or tocopherol or comparison of its efficacy in patients having atherosclerosis, dyslipidaemia leading to cardiovascular diseases, and studies including details of efficacy of any of the four alpha, beta, gamma, delta isomers of tocopherol or tocotrienol were included. Pertinent data from the eligible studies was retrieved and reviewed., Results: Of the 516 articles identified, 26 (5%) articles met eligibility criteria. Of them 5(19%) were subjected to detailed analysis. Tocotrienol showed significant anti-oxidant efficacy at (250 mg/d) by decreasing cholesterol and serum inflammatory biomarkers i.e C-reactive protein (40%), malondialdehyde (34%), gamma-glutamyl transferase (22%) (p<0.001). Total anti-oxidant status (TAS) levels raised 22% (p<0.001) and Inflammatory cytokines i.e resistin, interleukin (IL)-1, IL-12, Interferon-gamma were decreased 15-17% (p<0.05-0.01) respectively by tocotrienol. Several microRNA (miRNA-133a, miRNA-223, miRNA-214, miRNA-155) were modulated by δ-tocotrienol. Whereas, tocopherol showed heterogeneity of results by either decreasing or increasing the risk of mortality in atherosclerotic cardiovascular diseases., Conclusion: Compared to tocopherol, tocotrienol was found to be safe and potential candidate for improving cardiovascular health in the management of atherosclerotic cardiovascular diseases.
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- 2024
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34. Effectiveness of sirolimus in severe refractory chronic spontaneous urticaria.
- Author
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Patel G and Khan DA
- Subjects
- Humans, Female, Male, Adult, Middle Aged, Treatment Outcome, Immunosuppressive Agents therapeutic use, Sirolimus therapeutic use, Chronic Urticaria drug therapy
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- 2024
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35. Viral infection: A missed cause of chronic spontaneous urticaria?
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Chong AC, Khan DA, and Klausner JD
- Subjects
- Adult, Female, Humans, Male, Middle Aged, Urticaria diagnosis, Urticaria etiology, Virus Diseases diagnosis, Virus Diseases complications, Chronic Urticaria drug therapy
- Abstract
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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- 2024
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36. fMRI BOLD responses to film stimuli and their association with exhaled nitric oxide in asthma and health.
- Author
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Ritz T, Kroll JL, Khan DA, Yezhuvath US, Aslan S, Pinkham A, Rosenfield D, and Brown ES
- Subjects
- Humans, Nitric Oxide analysis, Oxygen, Emotions physiology, Magnetic Resonance Imaging, Asthma diagnostic imaging
- Abstract
Little is known about central nervous system (CNS) responses to emotional stimuli in asthma. Nitric oxide in exhaled breath (FE
NO ) is elevated in asthma due to allergic immune processes, but endogenous nitric oxide is also known to modulate CNS activity. We measured fMRI blood oxygen-dependent (BOLD) brain activation to negative (blood-injection-injury themes) and neutral films in 31 participants (15 with asthma). Regions-of-interest analysis was performed on key areas relevant to central adaptive control, threat processing, or salience networks, with dorsolateral prefrontal cortex (PFC), anterior insula, dorsal anterior cingulate cortex (dACC), amygdala, ventral striatum, ventral tegmentum, and periaqueductal gray, as well as top-down modulation of emotion, with ventrolateral and ventromedial PFC. Both groups showed less BOLD deactivation from fixation cross-baseline in the left anterior insula and bilateral ventromedial PFC for negative than neutral films, and for an additional number of areas, including the fusiform gyrus, for film versus recovery phases. Less deactivation during films followed by less recovery from deactivation was found in asthma compared to healthy controls. Changes in PCO2 did not explain these findings. FENO was positively related to BOLD activation in general, but more pronounced in healthy controls and more likely in neutral film processing. Thus, asthma is associated with altered processing of film stimuli across brain regions not limited to central adaptive control, threat processing, or salience networks. Higher levels of NO appear to facilitate CNS activity, but only in healthy controls, possibly due to allergy's masking effects on FENO ., (© 2024 Society for Psychophysiological Research.)- Published
- 2024
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37. Drug Allergy Mimics.
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Waldron JL, Glennon CM, Kroshinsky DA, Khan DA, and Wolfson AR
- Subjects
- Humans, Diagnosis, Differential, Diagnostic Errors, Drug Hypersensitivity Syndrome diagnosis, Lymphohistiocytosis, Hemophagocytic diagnosis, Lymphohistiocytosis, Hemophagocytic immunology, Drug Hypersensitivity diagnosis
- Abstract
When approaching a case of apparent drug allergy, the consulting clinician should consider a broad differential diagnosis. This article presents a series of cases that could be commonly referred to an allergist for assessment as "drug allergy," however, a real diagnosis exists that mandates a different diagnostic and treatment strategy, including a case of inducible laryngeal obstruction, multiple drug intolerance syndrome, viral rash, seizure due to metastatic malignancy, and hemophagocytic lymphohistiocytosis initially diagnosed as drug reaction and eosinophilia with systemic symptoms. The initial misdiagnoses of these patients delayed or interfered with their medical care, emphasizing the importance of accurate diagnoses for the benefit of our patients., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
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- 2024
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38. Severe Multiple Drug Intolerance Syndrome in Fibromyalgia and Irritable Bowel Syndrome.
- Author
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Alvarez AA, Palka JM, and Khan DA
- Subjects
- Humans, Female, Male, Middle Aged, Retrospective Studies, Adult, Drug Hypersensitivity epidemiology, Drug Hypersensitivity diagnosis, Risk Factors, Prevalence, Aged, Polypharmacy, Severity of Illness Index, Fibromyalgia epidemiology, Irritable Bowel Syndrome epidemiology
- Abstract
Background: Multiple drug intolerance syndrome (MDIS) describes patients with multiple nonimmunologically mediated adverse reactions to medications. Patients with more than 10 medication intolerance labels are considered to have severe MDIS. There is overlap in the characteristics of patients with MDIS and fibromyalgia and irritable bowel syndrome (IBS). Severe MDIS can limit treatment options in this already complex patient group., Objective: This study assessed the prevalence of severe MDIS in patients with fibromyalgia and IBS and its associated risk factors., Methods: A retrospective chart review identified patients diagnosed with fibromyalgia or IBS who had been seen at a large academic center from August 2019 to July 2020. Exact birthdate- and sex-matched controls who had been seen within the same time frame were selected at random. Listed drug intolerance data and patient characteristics were then analyzed with logistic regression and χ
2 testing., Results: Patients with fibromyalgia and IBS were 12 and 3 times more likely to have severe MDIS compared with controls, respectively. Severe MDIS was associated with polypharmacy in both groups. Opiates were the most frequently reported drug intolerance across all participants. Although patients with IBS more often reported gastrointestinal symptoms as adverse reactions, individuals with fibromyalgia did not more frequently report pain or behavioral changes as adverse reactions., Conclusions: There was an increased rate of severe MDIS in patients diagnosed with fibromyalgia and IBS. Additional studies are needed to better understand the morbidity of MDIS and how it can best be managed in patients with fibromyalgia and IBS., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)- Published
- 2024
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39. Biomedical semantic text summarizer.
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Kirmani M, Kour G, Mohd M, Sheikh N, Khan DA, Maqbool Z, Wani MA, and Wani AH
- Subjects
- Semantics, Information Storage and Retrieval, Natural Language Processing, Algorithms, Biomedical Research
- Abstract
Background: Text summarization is a challenging problem in Natural Language Processing, which involves condensing the content of textual documents without losing their overall meaning and information content, In the domain of bio-medical research, summaries are critical for efficient data analysis and information retrieval. While several bio-medical text summarizers exist in the literature, they often miss out on an essential text aspect: text semantics., Results: This paper proposes a novel extractive summarizer that preserves text semantics by utilizing bio-semantic models. We evaluate our approach using ROUGE on a standard dataset and compare it with three state-of-the-art summarizers. Our results show that our approach outperforms existing summarizers., Conclusion: The usage of semantics can improve summarizer performance and lead to better summaries. Our summarizer has the potential to aid in efficient data analysis and information retrieval in the field of biomedical research., (© 2024. The Author(s).)
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- 2024
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40. Reply.
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Khan DA and Blumenthal KG
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- 2024
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41. Driving pressure in mechanical ventilation: A review.
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Zaidi SF, Shaikh A, Khan DA, Surani S, and Ratnani I
- Abstract
Driving pressure (∆P) is a core therapeutic component of mechanical ventilation (MV). Varying levels of ∆P have been employed during MV depending on the type of underlying pathology and severity of injury. However, ∆P levels have also been shown to closely impact hard endpoints such as mortality. Considering this, conducting an in-depth review of ∆P as a unique, outcome-impacting therapeutic modality is extremely important. There is a need to understand the subtleties involved in making sure ∆P levels are optimized to enhance outcomes and minimize harm. We performed this narrative review to further explore the various uses of ∆P, the different parameters that can affect its use, and how outcomes vary in different patient populations at different pressure levels. To better utilize ∆P in MV-requiring patients, additional large-scale clinical studies are needed., Competing Interests: Conflict-of-interest statement: There is no conflict of interest associated with any of the senior author or other coauthors contributed their efforts in this manuscript., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)
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- 2024
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42. The efficacy of citalopram or escitalopram in patients with asthma and major depressive disorder.
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Agarwal CD, Palka JM, Gajewski AJ, Khan DA, and Brown ES
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- Humans, Adrenal Cortex Hormones therapeutic use, Antidepressive Agents therapeutic use, Treatment Outcome, Randomized Controlled Trials as Topic, Asthma drug therapy, Citalopram therapeutic use, Depressive Disorder, Major drug therapy, Escitalopram therapeutic use
- Abstract
Background: Major depressive disorder is common in people with asthma. Yet, few studies have evaluated depression treatment in those with asthma., Objective: To explore the relationship between antidepressant use, depressive symptoms, and asthma control, pooled data from 3 randomized trials of either citalopram or escitalopram were assessed., Methods: Linear fixed effects and binary logistic regression analyses were conducted with between-subject covariates including treatment group, (original) study, and demographics. The within-subject effect of visit, and a treatment group-visit (between-within) interaction effect, were also evaluated. Analyses were repeated in a high asthma exacerbation subgroup having at least 3 oral corticosteroid bursts in the previous 12 months. Outcomes included the Hamilton rating scale for depression (HAM-D
17 ), the 7-item asthma control questionnaire (ACQ), and oral corticosteroid use (yes or no)., Results: In the pooled sample (n = 255), the antidepressant treatment group exhibited lower HAM-D17 overall (P ≤ .001) and a lower likelihood for oral corticosteroid use (P ≤ .001) relative to the placebo group. In the high-exacerbation subgroup (n = 96), treatment group participants had lower overall asthma control questionnaire (P = .004) and HAM-D17 scores (P ≤ .001), and a lower likelihood of oral corticosteroid use (P = .003), relative to placebo participants. All treatment group interaction effects were not significant., Conclusion: Citalopram or escitalopram exhibited efficacy in reducing depressive symptoms and the need for rescue oral corticosteroids in patients with asthma and major depressive disorder. Future work should determine whether selective serotonin reuptake inhibitors are effective at improving asthma outcomes in those with asthma who are not depressed., Trial Registration: Clinicaltrials.gov Identifier: NCT00621946 and NCT01324700 (one study was conducted before ClinicalTrials.gov requirements)., Competing Interests: Disclosures The authors declare no conflicts of interest., (Copyright © 2023 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)- Published
- 2024
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43. United States Drug Allergy Registry (USDAR) grading scale for immediate drug reactions.
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Khan DA, Phillips EJ, Accarino JJ, Gonzalez-Estrada A, Otani IM, Ramsey A, Arroyo AC, Banerji A, Chow T, Liu AY, Stone CA Jr, and Blumenthal KG
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- Humans, United States epidemiology, Skin Tests, Anti-Bacterial Agents, Drug Hypersensitivity diagnosis, Anaphylaxis, Hypersensitivity, Immediate diagnosis
- Abstract
Background: There is no accepted grading system classifying the severity of immediate reactions to drugs., Objective: The purpose of this article is to present a proposed grading system developed through the consensus of drug allergy experts from the United States Drug Allergy Registry (USDAR) Consortium., Methods: The USDAR investigators sought to develop a consensus severity grading system for immediate drug reactions that is applicable to clinical care and research., Results: The USDAR grading scale scores severity levels on a scale of 0 to 4. A grade of no reaction (NR) is used for patients who undergo challenge without any symptoms or signs, and it would confirm a negative challenge result. A grade 0 reaction is indicative of primarily subjective complaints that are commonly seen with both historical drug reactions and during drug challenges, and it would suggest a low likelihood of a true drug allergic reaction. Grades 1 to 4 meet the criteria for a positive challenge result and may be considered indicative of a drug allergy. Grade 1 reactions are suggestive of a potential immediate drug reaction with mild symptoms. Grade 2 reactions are more likely to be immediate drug reactions of moderate severity. Grade 3 reactions have features suggestive of a severe allergic reaction, whereas grade 4 reactions are life-threatening reactions such as anaphylactic shock and fatal anaphylaxis., Conclusion: This proposed grading schema for immediate drug reactions improves on prior schemata by being developed specifically for immediate drug reactions and being easy to implement in clinical and research practice., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
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- 2023
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44. Drug allergy in older adults: A study from the United States Drug Allergy Registry.
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Accarino JJO, Ramsey A, Samarakoon U, Phillips E, Gonzalez-Estrada A, Otani IM, Fu X, Banerji A, Stone CA Jr, Khan DA, and Blumenthal KG
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- Male, Humans, Female, United States epidemiology, Aged, Prospective Studies, Penicillins adverse effects, Anti-Bacterial Agents adverse effects, Drug Hypersensitivity diagnosis, Drug Hypersensitivity epidemiology, Drug Hypersensitivity drug therapy, Hypersensitivity drug therapy
- Abstract
Background: Older adults have an increased risk of adverse drug reactions and negative effects associated with alternative antibiotic use. Although the number of antibiotic allergies reported increases with age, the characteristics and outcomes of older adults receiving drug allergy assessment are unknown., Objective: To assess the characteristics and outcomes of drug allergy evaluations in older adults., Methods: We considered patients aged above or equal to 65 years enrolled in the United States Drug Allergy Registry (USDAR), a US multisite prospective cohort (January 16, 2019 to February 28, 2022). Data were summarized using descriptive statistics., Results: Of 1678 USDAR participants from 5 sites, 406 older adults aged above or equal to 65 years (37% 65-69 years, 37% 70-74 years, 16% 75-79 years, and 10% ≥80 years) received 501 drug allergy assessments. USDAR older adults were primarily of female sex (69%), White (94%), and non-Hispanic (98%). Most USDAR older adults reported less than or equal to 1 infections per year (64%) and rated their general health as good, very good, or excellent (80%). Of 296 (59%) penicillin allergy assessments in USDAR older adults, 286 (97%) were disproved. Other drug allergy assessments included sulfonamide (n = 41, 88% disproved) and cephalosporin (n = 20, 95% disproved) antibiotics. All 41 drug allergy labels in USDAR participants aged above or equal to 80 years and all 80 penicillin allergy labels in USDAR men aged above or equal to 65 years were disproved., Conclusion: Older adults represented a quarter of USDAR participants but were neither racially nor ethnically diverse and were generally healthy without considerable antibiotic need. Most older adults presented for antibiotic allergy assessments, the vast majority of which were disproved. Drug allergy assessments may be underutilized in the older adults who are most vulnerable to the harms of unconfirmed antibiotic allergy labels., (Copyright © 2023 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
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- 2023
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45. Unpacking the importance of histopathology in ectopic pregnancy: Vital for follow up.
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Jain A, Khan DA, Khanday A, and Nigam A
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- Pregnancy, Female, Humans, Adult, Follow-Up Studies, Salpingectomy, Pregnancy, Ectopic diagnosis, Pregnancy, Ectopic surgery, Hydatidiform Mole diagnosis
- Abstract
The incidence of ectopic molar pregnancy is very rare with an incidence estimated to be 1.5 per 1,000,000 pregnancies. The pre-operative diagnosis is rare and needs careful histopathological examination of salpingectomy specimen. A case of a 34-year-old female is discussed who presented in shock with clinical and radiological diagnosis of ruptured ectopic pregnancy and histopathology report revealed partial mole in ectopic specimen.
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- 2023
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46. The Value of Current Laboratory Tests in Diagnosing Food, Venom, and Drug Allergies.
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Wang J, Golden DBK, and Khan DA
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- Humans, Immunoglobulin E, Allergens, Wasp Venoms, Anaphylaxis diagnosis, Drug Hypersensitivity diagnosis
- Abstract
An accurate diagnosis of IgE-mediated allergies is necessary to inform risk management for severe allergic reactions including anaphylaxis for food, venom, and drug allergies. The most widely available laboratory test for allergy is serum-specific IgE testing, which is routinely used for food allergy and insect sting allergy. Testing for specific IgE is limited by high sensitivity and low specificity, resulting in concern regarding overdiagnosis. Testing of allergen components has led to improved diagnosis for some food and venom allergens. Additional options for laboratory tests, such as epitope analysis, basophil activation, and mast cell activation, are being investigated for their potential to optimize diagnosis and provide predictors for reaction severity and treatment response. In contrast, laboratory testing for drug allergy is more limited because to date, there are no well-validated commercial assays in the United States. Furthermore, it is important to diagnose delayed reactions to medications, because these also significantly affect decision-making regarding therapeutic options for infectious disorders. Reliable tests for both immediate and delayed drug hypersensitivity are much needed, because drug allergy labels can significantly limit treatment options for patients. Research in this area is emerging., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
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- 2023
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47. Revolutionizing anti-cancer drug discovery against breast cancer and lung cancer by modification of natural genistein: an advanced computational and drug design approach.
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Akash S, Bibi S, Biswas P, Mukerjee N, Khan DA, Hasan MN, Sultana NA, Hosen ME, Jardan YAB, Nafidi HA, and Bourhia M
- Abstract
Breast and lung cancer are two of the most lethal forms of cancer, responsible for a disproportionately high number of deaths worldwide. Both doctors and cancer patients express alarm about the rising incidence of the disease globally. Although targeted treatment has achieved enormous advancements, it is not without its drawbacks. Numerous medicines and chemotherapeutic drugs have been authorized by the FDA; nevertheless, they can be quite costly and often fall short of completely curing the condition. Therefore, this investigation has been conducted to identify a potential medication against breast and lung cancer through structural modification of genistein. Genistein is the active compound in Glycyrrhiza glabra (licorice), and it exhibits solid anticancer efficiency against various cancers, including breast cancer, lung cancer, and brain cancer. Hence, the design of its analogs with the interchange of five functional groups-COOH, NH
2 and OCH3 , Benzene, and NH-CH2 -CH2 -OH-have been employed to enhance affinities compared to primary genistein. Additionally, advanced computational studies such as PASS prediction, molecular docking, ADMET, and molecular dynamics simulation were conducted. Firstly, the PASS prediction spectrum was analyzed, revealing that the designed genistein analogs exhibit improved antineoplastic activity. In the prediction data, breast and lung cancer were selected as primary targets. Subsequently, other computational investigations were gradually conducted. The mentioned compounds have shown acceptable results for in silico ADME, AMES toxicity, and hepatotoxicity estimations, which are fundamental for their oral medication. It is noteworthy that the initial binding affinity was only -8.7 kcal/mol against the breast cancer targeted protein (PDB ID: 3HB5). However, after the modification of the functional group, when calculating the binding affinities, it becomes apparent that the binding affinities increase gradually, reaching a maximum of -11.0 and -10.0 kcal/mol. Similarly, the initial binding affinity was only -8.0 kcal/mol against lung cancer (PDB ID: 2P85), but after the addition of binding affinity, it reached -9.5 kcal/mol. Finally, a molecular dynamics simulation was conducted to study the molecular models over 100 ns and examine the stability of the docked complexes. The results indicate that the selected complexes remain highly stable throughout the 100-ns molecular dynamics simulation runs, displaying strong correlations with the binding of targeted ligands within the active site of the selected protein. It is important to further investigate and proceed to clinical or wet lab experiments to determine the practical value of the proposed compounds., Competing Interests: The 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 © 2023 Akash, Bibi, Biswas, Mukerjee, Khan, Hasan, Sultana, Hosen, Jardan, Nafidi and Bourhia.)- Published
- 2023
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48. Association of serotonin reuptake inhibitors with asthma control.
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Gajewski AJ, Palka JM, Raitt JM, Agarwal CD, Khan DA, Kao CH, and Brown ES
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- Adult, Humans, Selective Serotonin Reuptake Inhibitors adverse effects, Prospective Studies, Retrospective Studies, Norepinephrine, Depressive Disorder, Major drug therapy, Depressive Disorder, Major epidemiology, Serotonin and Noradrenaline Reuptake Inhibitors, Asthma diagnosis, Asthma drug therapy, Asthma epidemiology
- Abstract
Background: Clinical trials demonstrated that selective serotonin reuptake inhibitors (SSRI) can improve asthma control in patients with comorbid major depressive disorder (MDD) and that this effect may be greater than the effect of SSRIs on depression. These findings suggest that SSRIs may improve asthma control in patients without MDD. Objective: The current retrospective study examined the effect of SSRIs and serotonin and norepinephrine reuptake inhibitors (SNRI) on asthma control in adult patients. We hypothesized that patients would have fewer asthma exacerbations after treatment with an SSRI or SNRI. Methods: Electronic health record data of adult patients (N = 592) who were seen at a University of Texas Southwestern (UTSW) hospital or clinic and had (1) an SSRI or SNRI prescription, (2) a previous asthma diagnosis, and (3) no mood disorder diagnosis were extracted by using the UTSW Clinical Data Exchange Network. Wilcoxon signed rank tests were used to compare oral corticosteroid prescriptions and asthma-related emergency department (ED) visits and hospitalizations in the 12 months before and after the start of an SSRI/SNRI. Results: Therapy with SSRIs/SNRIs was associated with a significant decrease in oral corticosteroid use (p = 0.003), ED visits (p = 0.002), and hospitalizations (p < 0.001). Conclusion: Results from the current study add to the existing literature by demonstrating a reduced rate of severe exacerbations in patients with asthma by using an SSRI/SNRI without limiting the analytic sample to a high-illness-severity subgroup defined by symptoms of asthma or depression. Future work should include a prospective, placebo controlled study with individuals who have asthma and no comorbid mental health condition, verified by a mental health professional.
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- 2023
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49. Updated guidance regarding the risk of allergic reactions to COVID-19 vaccines and recommended evaluation and management: A GRADE assessment and international consensus approach.
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Greenhawt M, Dribin TE, Abrams EM, Shaker M, Chu DK, Golden DBK, Akin C, Anagnostou A, ALMuhizi F, Alqurashi W, Arkwright P, Baldwin JL, Banerji A, Bégin P, Ben-Shoshan M, Bernstein J, Bingemann TA, Bindslev-Jensen C, Blumenthal K, Byrne A, Cahill J, Cameron S, Campbell D, Campbell R, Cavender M, Chan ES, Chinthrajah S, Comberiati P, Eastman JJ, Ellis AK, Fleischer DM, Fox A, Frischmeyer-Guerrerio PA, Gagnon R, Garvey LH, Grayson MH, Isabwe GAC, Hartog N, Hendron D, Horner CC, Hourihane JO, Iglesia E, Kan M, Kaplan B, Katelaris CH, Kim H, Kelso JM, Khan DA, Lang D, Ledford D, Levin M, Lieberman JA, Loh R, Mack DP, Mazer B, Mody K, Mosnaim G, Munblit D, Mustafa SS, Nanda A, Nathan R, Oppenheimer J, Otani IM, Park M, Pawankar R, Perrett KP, Peter J, Phillips EJ, Picard M, Pitlick M, Ramsey A, Rasmussen TH, Rathkopf MM, Reddy H, Robertson K, Rodriguez Del Rio P, Sample S, Sheshadri A, Sheik J, Sindher SB, Spergel JM, Stone CA, Stukus D, Tang MLK, Tracy JM, Turner PJ, Vander Leek TK, Wallace DV, Wang J, Wasserman S, Weldon D, Wolfson AR, Worm M, and Yacoub MR
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- Humans, COVID-19 Vaccines adverse effects, GRADE Approach, Consensus, Vaccine Excipients, Excipients, COVID-19 prevention & control, Hypersensitivity, Immediate, Anaphylaxis
- Abstract
This guidance updates 2021 GRADE (Grading of Recommendations Assessment, Development and Evaluation) recommendations regarding immediate allergic reactions following coronavirus disease 2019 (COVID-19) vaccines and addresses revaccinating individuals with first-dose allergic reactions and allergy testing to determine revaccination outcomes. Recent meta-analyses assessed the incidence of severe allergic reactions to initial COVID-19 vaccination, risk of mRNA-COVID-19 revaccination after an initial reaction, and diagnostic accuracy of COVID-19 vaccine and vaccine excipient testing in predicting reactions. GRADE methods informed rating the certainty of evidence and strength of recommendations. A modified Delphi panel consisting of experts in allergy, anaphylaxis, vaccinology, infectious diseases, emergency medicine, and primary care from Australia, Canada, Europe, Japan, South Africa, the United Kingdom, and the United States formed the recommendations. We recommend vaccination for persons without COVID-19 vaccine excipient allergy and revaccination after a prior immediate allergic reaction. We suggest against >15-minute postvaccination observation. We recommend against mRNA vaccine or excipient skin testing to predict outcomes. We suggest revaccination of persons with an immediate allergic reaction to the mRNA vaccine or excipients be performed by a person with vaccine allergy expertise in a properly equipped setting. We suggest against premedication, split-dosing, or special precautions because of a comorbid allergic history., (Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.)
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- 2023
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50. The One Health approach for allergic diseases and asthma.
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Jutel M, Mosnaim GS, Bernstein JA, Del Giacco S, Khan DA, Nadeau KC, Pali-Schöll I, Torres MJ, Zemelka-Wiacek M, and Agache I
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- Animals, Humans, Irritants, Allergens, One Health, Hypersensitivity epidemiology, Hypersensitivity etiology, Hypersensitivity therapy, Asthma epidemiology, Asthma etiology, Asthma therapy
- Abstract
The One Health approach is a collaborative and interdisciplinary strategy with focal point on human, animal, and environmental health interconnections. One Health can support the advanced management of allergic diseases and asthma, as complex, multifactorial diseases driven by interactions between the resilience response to the exposome. According to the One Health concept allergic diseases and asthma arising from exposures to a wide range of allergens, infectious agents and irritants (such as pollutants) occurring indoors and outdoors can be heavily influenced by environmental health (air, water, and soil quality) intermingled with animal health. These are currently heavily impacted by climate change, land use, urbanization, migration, overpopulation, and many more. Thus, a coordinated response to address the underlying factors that contribute to the development of allergic diseases and asthma needs to focus on the environment, human, and animal health altogether. Collaborative efforts across multiple sectors, including public health, veterinary medicine, environmental science, and community engagement are thus needed. A wide range of activities, including monitoring and surveillance of environmental and health data, targeted interventions to reduce exposures to allergens and irritants, and research on the underlying mechanisms that drive the development of allergic diseases and asthma are needed to move the field forward. In this consensus document elaborated by the European Academy of Allergy and Clinical Immunology (EAACI) and American Academy of Allergy, Asthma, and Immunology (AAAAI) under the practical allergy (PRACTALL) series, we provide insights into the One Heath approach aiming to provide a framework for addressing the complex and multifactorial nature of allergic diseases and asthma., (© 2023 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)
- Published
- 2023
- Full Text
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