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Tham T Le,1 David B Price,2– 4 Clement Erhard,5 Bill Cook,6 Anna Quinton,7 Rohit Katial,8 George C Christoff,9 Luis Perez-de-Llano,10 Alan Altraja,11,12 Celine Bergeron,13 Arnaud Bourdin,14 Mariko Siyue Koh,15,16 Lauri Lehtimäki,17,18 Bassam Mahboub,19 Nikolaos G Papadopoulos,20,21 Paul Pfeffer,22,23 Chin Kook Rhee,24 Victoria Carter,2,3 Neil Martin,25,26 Trung N Tran1 On behalf of the EVEREST Study Working Group1BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, MD, USA; 2Observational and Pragmatic Research Institute, Singapore; 3Optimum Patient Care Global, Cambridge, UK; 4Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK; 5BioPharmaceuticals Medical, AstraZeneca, Cambridge, UK; 6Respiratory and Immunology, BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, MD, USA; 7BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK; 8Global Medical Respiratory, BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, MD, USA; 9Faculty of Public Health, Medical University Sofia, Sofia, Bulgaria; 10Department of Respiratory Medicine, University Hospital Lucus Augusti, Lugo, Spain; 11Department of Pulmonology, University of Tartu, Tartu, Estonia; 12Lung Clinic, Tartu University Hospital, Tartu, Estonia; 13Centre for Lung Health, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada; 14PhyMedExp, University of Montpellier, CNRS, INSERM, University Hospital of Montpellier, Montpellier, France; 15Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore; 16Duke-NUS Medical School, Singapore; 17Allergy Centre, Tampere University Hospital, Tampere, Finland; 18Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; 19Rashid Hospital, Dubai Health Authority, Dubai, United Arab Emirates; 20Division of Infection, Immunity and Respiratory Medicine, University of Manchester, Manchester, UK; 21Allergy Department, 2nd Pediatric Clinic, University of Athens, Athens, Greece; 22Department of Respiratory Medicine, Barts Health NHS Trust, London, UK; 23Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK; 24Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Seoul St. Mary’s Hospital, College of Medicine, the Catholic University of Korea, Seoul, South Korea; 25Respiratory and Immunology, BioPharmaceuticals Medical, AstraZeneca, Cambridge, UK; 26University of Leicester, Leicester, UKCorrespondence: Trung N Tran, BioPharmaceuticals Medical, Respiratory and Immunology, AstraZeneca, Gaithersburg, MD, USA, Email trung.tran1@astrazeneca.comIntroduction: Patients with severe asthma may be prescribed biologic therapies to improve disease control. The EVEREST study aimed to characterize the global disease burden of patients with severe asthma without access to biologics and those who have access but do not receive biologics, as well as the remaining unmet need despite use of these therapies.Methods: This was a historical cohort study of patients with severe asthma (aged ≥ 18 years) in the International Severe Asthma Registry receiving Global Initiative for Asthma (GINA) 2018 step 5 treatment, or with uncontrolled disease at GINA step 4. Prospective data on patient clinical characteristics, healthcare resource utilization, and medication use over a 12-month period between December 2017 and May 2022 were assessed for the following five groups: biologics accessible (omalizumab, mepolizumab, reslizumab, benralizumab, or dupilumab); biologics inaccessible; biologics accessible but not received; biologics accessible and received; and biologic recipients whose asthma remained suboptimally controlled.Results: Overall, 9587 patients from 21 countries were included. Among patients in the biologics accessible (n=5073), biologics inaccessible (n=3041), and biologics accessible but not received (n=382) groups, 41.4%, 18.7%, and 49.6% experienced at least two exacerbations, 11.5%, 10.5%, and 6.2% required at least one hospitalization, 47.9%, 54.6%, and 71.2% had uncontrolled asthma, and 23.9%, 8.6%, and 11.0% received long-term oral corticosteroids (LTOCS), respectively. Following biologic therapy, among patients who received biologics overall (n=2666) and among those whose asthma remained suboptimally controlled (n=1780), 19.1% and 23.0% experienced at least two exacerbations, 2.7% and 2.9% required at least one hospitalization, and 16.7% and 22.0% received LTOCS, respectively.Conclusion: There is a substantial disease burden in both patients without access to biologics and those with access who do not receive these therapies, although specific outcomes may vary between these groups. There also remains a high unmet need among biologic recipients, many of whom have a suboptimal response to treatment.Keywords: biologic, disease burden, healthcare resource utilization, severe asthma

Trung N Tran,1 Heath Heatley,2 Arnaud Bourdin,3 Andrew Menzies-Gow,4,5 David J Jackson,6 Ekaterina Maslova,5 Jatin Chapaneri,5 William Henley,2,7 Victoria Carter,2 Jeffrey Shi Kai Chan,2 Cono Ariti,2 John Haughney,8,9 David Price2,9 1BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, MD, USA; 2Observational and Pragmatic Research Institute, Singapore; 3Department of Respiratory Diseases, PhyMedExp, University of Montpellier, Montpellier, France; 4Royal Brompton & Harefield Hospitals and School of Immunology & Microbial Sciences, King’s College London, London, UK; 5BioPharmaceuticals Medical, AstraZeneca, Cambridge, UK; 6Guy’s Severe Asthma Centre, Guy’s and St Thomas’ Hospitals, School of Immunology & Microbial Sciences, King’s College London, London, UK; 7Department of Health and Community Sciences University of Exeter Medical School, Exeter, UK; 8NHS Clinical Research Facilities, Glasgow, UK; 9Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UKCorrespondence: David Price, Observational and Pragmatic Research Institute, 22 Sin Ming Lane, &num;06-76, Midview City, 573969, Singapore, Tel +65 3105 1489, Email dprice@opri.sgPurpose: Oral corticosteroid (OCS) use for asthma is associated with considerable healthcare resource utilization (HCRU) and costs. However, no study has investigated this in relation to patterns of intermittent OCS prescription.Methods: This historical UK cohort study used primary care medical records, linked to Hospital Episode Statistics, from 2008 to 2019, of patients (≥ 4 years old) with asthma prescribed intermittent OCS. Patients were categorized by OCS prescribing pattern (one-off [single], less frequent [≥ 90-day gap] and frequent [< 90-day gap]) and matched 1:1 (by sex, age and index date) with people never prescribed OCS with/without asthma. HCRU (reported as episodes, except for length of hospital stay [days] and any prescription [records]) and associated costs were compared between intermittent OCS and non-OCS cohorts, and among intermittent OCS prescribing patterns.Results: Of 149,191 eligible patients, 50.3% had one-off, 27.4% less frequent, and 22.3% frequent intermittent OCS prescribing patterns. Annualized non-respiratory HCRU rates were greater in the intermittent OCS versus non-OCS cohorts for GP visits (5.93 vs 4.70 episodes, p < 0.0001), hospital admissions (0.24 vs 0.16 episodes, p < 0.0001), and length of stay (1.87 vs 1.58 days, p < 0.0001). In the intermittent OCS cohort, rates were highest in the frequent prescribing group for GP visits (7.49 episodes; p < 0.0001 vs one-off), length of stay (2.15 days; p < 0.0001) and any prescription including OCS (25.22 prescriptions; p < 0.0001). Mean per-patient non-respiratory related and all-cause HCRU-related costs were higher with intermittent OCS than no OCS (£ 3902 vs £ 2722 and £ 8623 vs £ 4929, respectively), as were mean annualized costs (£ 565 vs £ 313 and £ 1526 vs £ 634, respectively). A dose–response relationship existed; HCRU-related costs were highest in the frequent prescribing cohort (p < 0.0001).Conclusion: Intermittent OCS use and more frequent intermittent OCS prescription patterns were associated with increased HCRU and associated costs. Improved asthma management is needed to reduce reliance on intermittent OCS in primary care.Keywords: asthma, costs, healthcare resource utilization, intermittent, oral corticosteroids

Tham T Le,1 Benjamin Emmanuel,1 Rohit Katial,2 Trung N Tran,1 Justin Joseph Kwiatek,1 David S Cohen,1 Shoshana R Daniel,3 Yunhui Cao,1 Vivian H Shih,1 Maria Gil Melcón,4 Gilles Devouassoux,5 Girolamo Pelaia6 On behalf of the RANS Study Investigators1BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, MD, USA; 2Center for Clinical Immunology, National Jewish Health & University of Colorado School of Medicine, Denver, CO, USA; 3Market Access Consulting, Fortrea Inc., Durham, NC, USA; 4Otorhinolaryngology and Head and Neck Surgery Department, University Hospital of Salamanca, Salamanca, Spain; 5Department of Pulmonology, Hospices Civils de Lyon (HCL), Hôpital de la Croix-Rousse, Lyon, and F-CRIN INSERM Network CRISALIS, Toulouse, France; 6Department of Health Sciences, University “Magna Graecia” of Catanzaro, Catanzaro, ItalyCorrespondence: Girolamo Pelaia, University “Magna Graecia” of Catanzaro, Viale Europa, 88100 Catanzaro, Italy, Tel +39 961 3647171, Fax +39 961 3647193, Email pelaia@unicz.itPurpose: Real-world evidence of benralizumab effectiveness on nasal polyps (NP) and asthma outcomes in patients with severe eosinophilic asthma (SEA) and comorbid chronic rhinosinusitis with NP are limited. The objective of this study was to assess NP and asthma outcomes in benralizumab-treated patients with SEA and comorbid NP in a real-world setting.Patients and Methods: RANS was a retrospective, multi-country observational study (ClinicalTrials.gov: NCT05180357) using medical chart reviews of adults with SEA and comorbid NP. Total NP Score (NPS), SinoNasal Outcome Test-22 (SNOT-22) total score, annualized exacerbation rate (AER), and 6-item Asthma Control Questionnaire (ACQ-6) and Asthma Control Test (ACT) scores during the 12 months pre-index (baseline) and post-index (follow-up) were measured. Clinically meaningful improvement from baseline following treatment, in terms of total NPS (≥ 1-point reduction), SNOT-22 total (≥ 8.9-point reduction), ACQ-6 (≥ 0.5-point reduction) or ACT (≥ 3-point increase) scores, were reported.Results: A total of 233 patients were included. Baseline mean (standard deviation [SD]) NPS and SNOT-22 total scores were 3.8 (2.4) and 47.5 (22.6), respectively. The mean change (95% confidence interval [CI]) from baseline was – 1.2 (– 1.7, – 0.6) for NPS, and – 19.8 (– 23.6, – 15.9) for SNOT-22. The AER (95% CI) was 1.2 (0.96, 1.41) at baseline and 0.2 (0.13, 0.28) at follow-up. Mean (SD) ACQ-6 and ACT scores were 1.6 (1.3) and 15.0 (5.2) at baseline and 0.8 (1.0) and 22.0 (3.9) at follow-up, respectively. The proportion of patients who achieved clinically meaningful improvements in NPS, SNOT-22 total, ACQ-6, and ACT scores was 49.1%, 67.6%, 56.6%, and 81.1%, respectively.Conclusion: In this real-world study, improvements in NP and asthma outcomes in patients with SEA and comorbid NP were observed during the 12 months following benralizumab initiation.Keywords: exacerbations, comorbidity, biologics, patient-reported outcomes, SinoNasal Outcome Test-22, Nasal Polyps Score

Andrew N Menzies-Gow,1,2 Trung N Tran,3 Brooklyn Stanley,4 Victoria Ann Carter,4 Josef S Smolen,5 Arnaud Bourdin,6 J Mark Fitzgerald7 ,† Tim Raine,8 Jatin Chapaneri,2 Benjamin Emmanuel,3 David J Jackson,9,10 David B Price4,11 1Royal Brompton and Harefield Hospitals, Guys & St Thomas’ NHS Foundation Trust, London, UK; 2AstraZeneca, Cambridge, UK; 3AstraZeneca, Gaithersburg, MD, USA; 4Observational and Pragmatic Research Institute, Singapore; 5Medical University of Vienna, Vienna, Austria; 6Université de Montpellier, CHU Montpellier, PhyMedExp, INSERM, CNRS, Montpellier, France; 7The University of British Columbia, Vancouver, British Columbia, Canada; 8Cambridge University Hospitals NHS Foundation Trust, Addenbrooke’s Hospital, Cambridge, UK; 9Guy’s Severe Asthma Centre, Guy’s & St Thomas’ NHS Trust, London, UK; 10School of Immunology & Microbial Sciences, King’s College London, London, UK; 11Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK†J. Mark Fitzgerald passed away on January 18, 2022Correspondence: David B Price, Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Polwarth Building-Foresterhill, Aberdeen, AB25 2ZD, UK, Tel +65 3105 1489, Email dprice@opri.sgPurpose: Associations between systemic glucocorticoid (SGC) exposure and risk for adverse outcomes have spurred a move toward steroid-sparing treatment strategies. Real-world changes in SGC exposure over time, after the introduction of steroid-sparing treatment strategies, reveal areas of successful risk mitigation as well as unmet needs.Patients and Methods: A population-based ecological study was performed from the Optimum Patient Care Research Database to describe SGC prescribing trends of steroid-sparing treatment strategies in primary care practices before and after licensure of biologics in the United Kingdom from 1990 to 2019. Each analysis year included patients aged ≥ 5 years who were registered for ≥ 1 year with a participating primary care practice. The primary analysis was SGC exposure, defined as total cumulative SGC dose per patient per year, for asthma, severe asthma, chronic obstructive pulmonary disease (COPD), nasal polyps, Crohn’s disease, rheumatoid arthritis, ulcerative colitis, and systemic lupus erythematosus. Secondary outcomes were percentages of patients prescribed SGCs and number of SGC prescriptions per patient per year.Results: The number of patients who met study inclusion criteria ranged from 219,862 (1990) to 1,261,550 (2019). At the population level, patients with asthma or COPD accounted for 67.7% to 73.2% of patients per year with an SGC prescription. Over three decades, decreases in SGC total yearly dose ≥ 1000 mg have been achieved in multiple conditions. Patients with COPD prescribed SGCs increased from 5.8% (1990) to 34.8% (2017). SGC prescribing trends for severe asthma, Crohn’s disease, and ulcerative colitis show decreased prescribing trends after the introduction of biologics.Conclusion: Decreases in total yearly SGC doses have been shown in multiple conditions; however, for conditions such as severe asthma and COPD, an unmet need remains for increased awareness of SGC burden and the adoption or development of SGC-sparing alternatives to reduce overuse.Keywords: glucocorticoids, practice patterns, drug prescriptions, biological products, drug utilization

Breda Cushen,1,&ast; Mariko Siyue Koh,2,&ast; Trung N Tran,3 Neil Martin,3,4 Ruth Murray,5 Thendral Uthaman,6 Celine Yun Yi Goh,5,6 Rebecca Vella,7 Neva Eleangovan,5,6 Lakmini Bulathsinhala,5,6 Jorge F Maspero,8,9 Matthew J Peters,10 Florence Schleich,11 Paulo Pitrez,12 George Christoff,13 Mohsen Sadatsafavi,14 Carlos A Torres-Duque,15,16 Celeste Porsbjerg,17 Alan Altraja,18 Lauri Lehtimäki,19 Arnaud Bourdin,20 Christian Taube,21 Nikolaos G Papadopoulos,22,23 Csoma Zsuzsanna,24 Unnur Björnsdóttir,25 Sundeep Salvi,26 Enrico Heffler,27 Takashi Iwanaga,28 Mona al-Ahmad,29 Désirée Larenas-Linnemann,30 Job FM van Boven,31 Bernt Bøgvald Aarli,32,33 Piotr Kuna,34 Cláudia Chaves Loureiro,35,36 Riyad Al-lehebi,37 Jae Ha Lee,38 Nuria Marina,39 Leif Bjermer,40 Chau-Chyun Sheu,41,42 Bassam Mahboub,43 John Busby,44 Andrew Menzies-Gow,45 Eileen Wang,46 David B Price5,6,47 On behalf of ISAR Inventory Study Group1Department of Respiratory Medicine, Beaumont Hospital, Dublin, Ireland; 2Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore, Singapore; 3AstraZeneca, Gaithersburg, MD, USA; 4Department of Respiratory Medicine, University of Leicester, Leicester, UK; 5Optimum Patient Care Global, Cambridge, UK; 6Observational Pragmatic Research Institute, Singapore, Singapore; 7Optimum Patient Care, Brisbane, Queensland, Australia; 8Clinical Research for Allergy and Respiratory Medicine, CIDEA Foundation, Buenos Aires, Argentina; 9University Career of Specialists in Allergy and Clinical Immunology at the Buenos Aires University School of Medicine, Buenos Aires, Argentina; 10Department of Thoracic Medicine, Concord Hospital, Sydney, Australia; 11CHU Sart-Tilman, GIGA I3, University of Liege, Liège, Wallonia, Belgium; 12Pulmonology Division, Hospital Santa Casa de Porto Alegre, Porto Alegre, Brazil; 13Faculty of Public Health, Medical University, Sofia, Bulgaria; 14Respiratory Evaluation Sciences Program, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, Canada; 15CINEUMO, Respiratory Research Center, Fundación Neumológica Colombiana, Bogotá, Colombia; 16Universidad de La Sabana, Chia, Colombia; 17Department of Respiratory Medicine and Infectious Diseases, Research Unit, Bispebjerg Hospital, Copenhagen, Denmark; 18Department of Pulmonology, University of Tartu and Lung Clinic, Tartu University Hospital, Tartu, Estonia; 19Allergy Centre, Tampere University Hospital, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; 20PhyMedExp, Univ Montpellier, CNRS, INSERM, CHU Montpellier, Montpellier, France; 21Department of Pulmonary Medicine, University Medical Center Essen-Ruhrlandklinik, Essen, Germany; 22Division of Infection, Immunity & Respiratory Medicine, University of Manchester, Manchester, UK; 23Allergy Department, 2nd Pediatric Clinic, University of Athens, Athens, Greece; 24Asthma Outpatient Clinic, National Koranyi Institute for Pulmonology, Budapest, Hungary; 25Department of Allergy and Respiratory Medicine, University Hospital, Reykjavik, Iceland; 26Pulmocare Research and Education Foundation, Pune, India; 27Personalized Medicine, Asthma and Allergy, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy; 28Kindai University Hospital, Osakasayama, Japan; 29Microbiology Department, College of Medicine, Kuwait University, Kuwait, Al-Rashed Allergy Center, Ministry of Health, Kuwait City, Kuwait; 30Centro de Excelencia en Asma y Alergia, Hospital Médica Sur, Ciudad de México, Mexico; 31University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Department of Clinical Pharmacy & Pharmacology, Groningen, the Netherlands; 32Department of Thoracic Medicine, Haukeland University Hospital, Bergen, Norway; 33Department of Clinical Science, University of Bergen, Bergen, Norway; 34Division of Internal Medicine Asthma and Allergy, Medical University of Lodz, Lodz, Poland; 35Pneumology Unit, Hospitais da Universidade de Coimbra, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal; 36Centre of Pneumology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal; 37Department of Pulmonology, King Fahad Medical City, Riyadh, Saudi Arabia, Alfaisal University, Riyadh, Saudi Arabia; 38Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea; 39Pneumology Service, Biocruces, Cruces University Hospital, Barakaldo, Spain; 40Respiratory Medicine and Allergology, Department of Clinical Sciences, Skåne University Hospital, Lund University, Lund, Sweden; 41Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; 42Department of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 43Rashid Hospital, Dubai Health Authority (DHA), Dubai, United Arab Emirates; 44Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Belfast, Northern Ireland, UK; 45Lung Division, Royal Brompton & Harefield Hospital, London, UK; 46Division of Allergy and Clinical Immunology, Department of Medicine, National Jewish Health and University of Colorado School of Medicine, Denver and Aurora, CO, USA; 47Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, Scotland, UK&ast;These authors contributed equally to this workCorrespondence: David B Price, Observational and Pragmatic Research Institute (OPRI) Pte Ltd, 22 Sin Ming Lane, &num;06-76, Midview City, 573969, Singapore, Tel +65 3105 1489, Email dprice@opri.sgAim: The International Severe Asthma Registry (ISAR; http://isaregistries.org/) uses standardised variables to enable multi-country and adequately powered research in severe asthma. This study aims to look at the data countries within ISAR and non-ISAR countries reported collecting that enable global research that support individual country interests.Methods: Registries were identified by online searches and approaching severe asthma experts. Participating registries provided data collection specifications or confirmed variables collected. Core variables (results from ISAR’s Delphi study), steroid-related comorbidity variables, biologic safety variables (serious infection, anaphylaxis, and cancer), COVID-19 variables and additional variables (not belonging to the aforementioned categories) that registries reported collecting were summarised.Results: Of the 37 registries identified, 26 were ISAR affiliates and 11 non-ISAR affiliates. Twenty-five ISAR-registries and 4 non-ISAR registries reported collecting > 90% of the 65 core variables. Twenty-three registries reported collecting all optional steroid-related comorbidity variables. Twenty-nine registries reported collecting all optional safety variables. Ten registries reported collecting COVID-19 variables. Twenty-four registries reported collecting additional variables including data from asthma questionnaires (10 Asthma Control Questionnaire, 20 Asthma Control Test, 11 Asthma Quality of Life Questionnaire, and 4 EuroQol 5-dimension 5-level Questionnaire). Eight registries are linked to databases such as electronic medical records and national claims or disease databases.Conclusion: Standardised data collection has enabled individual severe asthma registries to collect unified data and increase statistical power for severe asthma research irrespective of ISAR affiliations.Keywords: Asia-Pacific, biologics, COVID-19, Europe, ISAR, International Severe Asthma Registry, oral corticosteroids, Registry, Middle East, Severe Asthma, Latin America, USA

Wenjia Chen,1 Mohsen Sadatsafavi,2 Trung N Tran,3 Ruth B Murray,4 Chong Boon Nigel Wong,1 Nasloon Ali,4,5 Cono Ariti,4,5 Esther Garcia Gil,6 Anthony Newell,5,7 Marianna Alacqua,8 Mona Al-Ahmad,9 Alan Altraja,10 Riyad Al-Lehebi,11,12 Mohit Bhutani,13 Leif Bjermer,14 Anne Sofie Bjerrum,15 Arnaud Bourdin,16 Lakmini Bulathsinhala,4,5 Anna von Bülow,17 John Busby,18 Giorgio Walter Canonica,19,20 Victoria Carter,4,5 George C Christoff,21 Borja G Cosio,22 Richard W Costello,23 J Mark FitzGerald,24 João A Fonseca,25 Kwang Ha Yoo,26 Liam G Heaney,27 Enrico Heffler,19,20 Mark Hew,28,29 Ole Hilberg,30 Flavia Hoyte,31,32 Takashi Iwanaga,33 David J Jackson,34,35 Rupert C Jones,36 Mariko Siyue Koh,37,38 Piotr Kuna,39 Désirée Larenas-Linnemann,40 Sverre Lehmann,41 Lauri A Lehtimäki,42,43 Juntao Lyu,5,7 Bassam Mahboub,44,45 Jorge Maspero,46,47 Andrew N Menzies-Gow,48 Concetta Sirena,49 Nikolaos Papadopoulos,50,51 Andriana I Papaioannou,52 Luis Pérez de Llano,53,54 Diahn-Warng Perng,55,56 Matthew Peters,57 Paul E Pfeffer,58,59 Celeste M Porsbjerg,17 Todor A Popov,60 Chin Kook Rhee,61 Sundeep Salvi,62 Camille Taillé,63 Christian Taube,64 Carlos A Torres-Duque,65 Charlotte S Ulrik,66 Seung Won Ra,67 Eileen Wang,31,32 Michael E Wechsler,68 David B Price4,5,69 1Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore; 2Respiratory Evaluation Sciences Program, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada; 3AstraZeneca, Gaithersburg, MD, USA; 4Optimum Patient Care, Cambridge, UK; 5Observational and Pragmatic Research Institute, Singapore, Singapore; 6AstraZeneca, Barcelona, Spain; 7Optimum Patient Care, Queensland, VIC, Australia; 8AstraZeneca, Cambridge, UK; 9Microbiology Department, Faculty of Medicine, Kuwait University, Al-Rashed Allergy Center, Ministry of Health, Kuwait City, Kuwait; 10Department of Pulmonology, University of Tartu and Lung Clinic, Tartu University Hospital, Tartu, Estonia; 11Department of Pulmonology, King Fahad Medical City, Riyadh, Saudi Arabia; 12College of Medicine, Alfaisal University, Riyadh, Saudi Arabia; 13Department of Medicine, Division of Pulmonary Medicine, University of Alberta, Western Canada, AB, Canada; 14Department of Clinical Sciences, Respiratory Medicine and Allergology, Skåne University Hospital, Lund University, Lund, Sweden; 15Department of Respiratory Medicine and Allergy, Aarhus University Hospital, Jutland, Aarhus, Denmark; 16PhyMedExp, Univ Montpellier, CNRS, INSERM, CHU Montpellier, Montpellier, France; 17Respiratory Research Unit, Bispebjerg University Hospital, Copenhagen, Denmark; 18Centre for Public Health, Queen’s University Belfast, Belfast, Northern Ireland; 19Personalized Medicine, Asthma and Allergy, Humanitas Clinical and Research Center IRCCS, Milan, Italy; 20Department of Biomedical Sciences, Humanitas University, Milan, Italy; 21Medical University-Sofia, Faculty of Public Health, Sofia, Bulgaria; 22Son Espases University Hospital-IdISBa-Ciberes, Mallorca, Spain; 23Department of Respiratory Medicine, Clinical Research Centre, Smurfit Building Beaumont Hospital, RCSI, Dublin, Ireland; 24Department of Medicine, the University of British Columbia, Vancouver, BC, Canada; 25Comunity Health, Information and Decision Sciences Department (MEDCIDS) & Center for Health Technology and Services Research (CINTESIS), Faculty of Medicine of University of Porto, Porto, Portugal; 26KonKuk University School of Medicine in Seoul, Seoul, Korea; 27Wellcome-Wolfson Centre for Experimental Medicine, Queen’s University Belfast, Belfast, Northern Ireland; 28Allergy, Asthma & Clinical Immunology Service, Alfred Health, Melbourne, VIC, Australia; 29Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia; 30Medical Department, Vejle University Hospital, Jutland, Vejle, Denmark; 31Department of Medicine, Division of Allergy and Clinical Immunology, National Jewish Health, Denver, CO, USA; 32Department of Internal Medicine, Division of Allergy & Clinical Immunology, University of Colorado School of Medicine, Aurora, CO, USA; 33Center for General Medical Education and Clinical Training, Kindai University Hospital, Osakasayama, Japan; 34UK Severe Asthma Network and National Registry, Guy’s and St Thomas’ NHS Trust, London, UK; 35School of Immunology & Microbial Sciences, King’s College London, London, UK; 36Research and Knowledge Exchange, Plymouth Marjon University, Plymouth, UK; 37Respiratory & Critical Care Medicine, Singapore General Hospital, Singapore, Singapore; 38SingHealth Duke-NUS Lung Centre, Singapore, Singapore; 39Division of Internal Medicine, Asthma and Allergy Medical University of &Lstrok;ód&zacute;, &Lstrok;ód&zacute;, Poland; 40Directora Centro de Excelencia en Asma y Alergia, Hospital Médica Sur, Ciudad de México, Mexico; 41Section of Thoracic Medicine, Department of Clinical Science, University of Bergen, Bergen, Norway; 42Allergy Centre, Tampere University Hospital, Tampere, Finland; 43Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; 44College of Medicine, University of Sharjah, Sharjah, United Arab Emirates; 45Rashid Hospital, Dubai Health Authority, Dubai, United Arab Emirates; 46Clinical Research for Allergy and Respiratory Medicine, CIDEA Foundation, Buenos Aires, Argentina; 47University Career of Specialists in Allergy and Clinical Immunology at the Buenos Aires University School of Medicine, Buenos Aires, Argentina; 48Royal Brompton & Harefield Hospitals, London, UK; 49Severe Asthma Network in Italy (SANI), Milano, Italy; 50Division of Infection, Immunity & Respiratory Medicine, University of Manchester, Manchester, UK; 51Allergy Department, 2nd Pediatric Clinic, University of Athens, Athens, Greece; 52 2nd Respiratory Medicine Department, National and Kapodistrian University of Athens Medical School, Attikon University Hospital, Athens, Greece; 53Pneumology Service, Lucus Augusti University Hospital, EOXI Lugo, Lugo, Spain; 54Biodiscovery Research Group, Health Research Institute of Santiago de Compostela, Santiago de Compostela, Spain; 55Division of Clinical Respiratory Physiology Chest Department, Taipei Veterans General Hospital, Taipei, Taiwan; 56COPD Assembly of the Asian Pacific Society of Respirology Hongo, Bunkyo-ku, Tokyo, Japan; 57Department of Thoracic Medicine, Concord Hospital, Sydney, NSW, Australia; 58Department of Respiratory Medicine, Barts Health NHS Trust, London, UK; 59Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK; 60University Hospital ”sv. Ivan Rilski”, Sofia, Bulgaria; 61Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Seoul St. Mary’s Hospital, College of Medicine, the Catholic University of Korea, Seoul, South Korea; 62Pulmocare Research and Education Foundation, Pune, India; 63Department of Respiratory Diseases, Bichat Hospital, AP-HP Nord-Université de Paris, Paris, France; 64Department of Pulmonary Medicine, University Medical Center Essen-Ruhrlandklinik, Essen, Germany; 65CINEUMO, Respiratory Research Center, Fundación Neumológica Colombiana, Bogotá, Colombia; 66Department of Respiratory Medicine, Copenhagen University Hospital-Hvidovre, Hvidovre, Denmark; 67Department of Internal Medicine, Division of Pulmonology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea; 68Department of Medicine, NJH Cohen Family Asthma Institute, National Jewish Health, Denver, CO, USA; 69Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UKCorrespondence: David B Price, Observational and Pragmatic Research Institute, 22 Sin Ming Lane, &num;06 Midview City, Singapore, Singapore, 573969, Tel +65 3105 1489, Email dprice@opri.sgBackground: Many severe asthma patients with high oral corticosteroid exposure (HOCS) often do not initiate biologics despite being eligible. This study aimed to compare the characteristics of severe asthma patients with HOCS who did and did not initiate biologics.Methods: Baseline characteristics of patients with HOCS (long-term maintenance OCS therapy for at least 1 year, or ≥ 4 courses of steroid bursts in a year) from the International Severe Asthma Registry (ISAR; https://isaregistries.org/), who initiated or did not initiate biologics (anti-lgE, anti-IL5/5R or anti-IL4R), were described at the time of biologic initiation or registry enrolment. Statistical relationships were tested using Pearson’s chi-squared tests for categorical variables, and t-tests for continuous variables, adjusting for potential errors in multiple comparisons.Results: Between January 2015 and February 2021, we identified 1412 adult patients with severe asthma from 19 countries that met our inclusion criteria of HOCS, of whom 996 (70.5%) initiated a biologic and 416 (29.5%) did not. The frequency of biologic initiation varied across geographical regions. Those who initiated a biologic were more likely to have higher blood eosinophil count (483 vs 399 cells/μL, p=0.003), serious infections (49.0% vs 13.3%, p< 0.001), nasal polyps (35.2% vs 23.6%, p< 0.001), airflow limitation (56.8% vs 51.8%, p=0.013), and uncontrolled asthma (80.8% vs 73.2%, p=0.004) despite greater conventional treatment adherence than those who did not start a biologic. Both groups had similar annual asthma exacerbation rates in the previous 12 months (5.7 vs 5.3, p=0.147).Conclusion: Around one third of severe HOCS asthma patients did not receive biologics despite a similar high burden of asthma exacerbations as those who initiated a biologic therapy. Other disease characteristics such as eosinophilic phenotype, serious infectious events, nasal polyps, airflow limitation and lack of asthma control appear to dictate biologic use.Keywords: severe asthma, biologics, real-world, treatment pattern, patient characteristics

Thua Nguyen Tran,1 Huu Dang Tran,2 Thanh Tung Tran-Huu,2 Duc Minh Tran,1 Quang Nhat Tran1 1Department of General Internal Medicine and Geriatrics, Hue Central Hospital, Hue City, Vietnam; 2Department of Internal Medicine, Hue University of Medicine and Pharmacy, Hue City, VietnamCorrespondence: Thua Nguyen Tran, Department of General Internal Medicine and Geriatrics, Hue Central Hospital, 16 Le Loi Street, Hue City, 530000, Vietnam, Tel +84903597695, Email tranthuanguyen23@gmail.comBackground: Metabolic syndrome is one of the most common public health concerns in the 21st century. Several previous studies have shown an association between increased serum ferritin levels and other components of metabolic syndrome and the risk of metabolic syndrome. They conclude that ferritin can be viewed as a predictor of metabolic syndrome risk. This study investigates some main features of metabolic syndrome and the serum ferritin levels in a Vietnamese adult cohort with metabolic syndrome.Methods: A descriptive cross-sectional study was conducted on 207 patients who were treated at the General Internal Medicine-Geriatric Department, Hue Central Hospital, from May 2018 to August 2020. Patients were divided into two groups: the study group (104 patients with metabolic syndrome) and the control group (103 patients without metabolic syndrome and no serum ferritin-mediated disease). The metabolic syndrome was diagnosed by a joint interim statement of the International Diabetes Federation/American Heart Association/National Heart, Lung, and Blood Institute/World Heart Federation/International Atherosclerosis Society/International Association for the Study of Obesity in 2009.Results: Hypertriglyceridemia–hypertension–hyperglycemia (50.9%) is the most common combination of metabolic syndrome components. The mean serum ferritin concentration was 391.62± 181.97ng/mL and 124.55± 63.95ng/mL in the metabolic syndrome and control groups, respectively. In the metabolic syndrome group, increased ferritin concentration accounted for 86.54% for men, the mean serum ferritin concentration was 453.064 ± 161.75ng/mL (increased ferritin concentration accounted for 96.15%) for women; the mean serum ferritin concentration was 330.17 ± 181.71 ng/mL (increased ferritin concentration accounted for 86.54%).Conclusion: The serum ferritin level is significantly increased in Vietnamese patients with metabolic syndrome.Keywords: metabolic syndrome, ferritin, hypertension

Quang Tuan Pham,1 Thua Nguyen Tran,2 Thanh Thuy Le-Thi,1 Anh Khoa Phan,3 Anh Vu Nguyen4 1Cardiology Department, Hue Central Hospital, Hue City, Vietnam; 2Department of General Internal Medicine and Geriatrics, Hue Central Hospital, Hue City, Vietnam; 3Emergency Department of Cardiovascular Intervention, Hue Central Hospital, Hue City, Vietnam; 4Cardiovascular Center, Hospital of University of Medicine and Pharmacy, Hue City, VietnamCorrespondence: Thua Nguyen Tran, Department of General Internal Medicine and Geriatrics, Hue Central Hospital, Hue City, Vietnam, Tel +84 903597695, Email tranthuanguyen23@gmail.comObjectives: To assess left ventricular diastolic function by using echocardiography in patients with dilated cardiomyopathy, and the relationship between left ventricular diastolic function and left ventricular dilatation, New York Heart Association (NYHA) heart failure index, left ventricular ejection fraction, and left ventricular fractional shortening.Methods: A descriptive cross-sectional study was conducted on patients with primary dilated cardiomyopathy hospitalized in Hue Central Hospital from April 2018 to August 2020.Results: The mean end-diastolic left ventricular volume was 133.57± 31.58 mL and the mean end-systolic left ventricular volume was 99.9± 26.03 mL. The mean left atrial volume was 61.63± 27.13 mL. The mean end-diastolic and end-systolic left ventricular diameters were 66.11± 7.3 mm and 57.7± 8.02 mm, respectively. The mean left ventricular ejection fraction was 24.68± 5.97%. The mean left ventricular fractional shortening was 12.91± 4.55%. The highest rate was grade II diastolic dysfunction (44.6%), followed by grade III diastolic dysfunction (35.8%) and grade I diastolic dysfunction at 19.6%. There was a moderate positive correlation between the left ventricular diastolic dysfunction and the NYHA class of heart failure with r=0.445, p< 0.001. All dilated cardiomyopathy patients in the study group had mainly grade II–III severe diastolic dysfunction.Conclusions: Routine evaluation of diastolic function in patients with heart failure can help in elucidation of pathogenesis and management of patients. This dysfunction was clearly demonstrated by the change in the parameters of the evaluation of left ventricular diastolic function on echocardiography according to the 2016 ASE/EACVI recommendations, a new recommendation introduced to approach the assessment of diastolic function in a more convenient and easier way.Keywords: dilated cardiomyopathy, left ventricular diastolic dysfunction

Andrew N Menzies-Gow,1 Claire McBrien,2 Bindhu Unni,3 Celeste M Porsbjerg,4 Mona Al-Ahmad,5 Christopher S Ambrose,6 Karin Dahl Assing,7 Anna von Bülow,4 John Busby,8 Borja G Cosio,9 J Mark FitzGerald,10 Esther Garcia Gil,11 Susanne Hansen,12 Liam G aHeaney,8 Mark Hew,13,14 David J Jackson,15,16 Maria Kallieri,17 Stelios Loukides,17 Njira L Lugogo,18 Andriana I Papaioannou,17 Désirée Larenas-Linnemann,19 Wendy C Moore,20 Luis A Perez-de-Llano,21 Linda M Rasmussen,22 Johannes M Schmid,23 Salman Siddiqui,24 Marianna Alacqua,25 Trung N Tran,6 Charlotte Suppli Ulrik,26 John W Upham,27 Eileen Wang,28,29 Lakmini Bulathsinhala,3,30 Victoria A Carter,3,30 Isha Chaudhry,3,30 Neva Eleangovan,3,30 Ruth B Murray,3,30 Chris A Price,3,30 David B Price3,30,31 1UK Severe Asthma Network and National Registry, Royal Brompton & Harefield Hospitals, London, UK; 2Kingston Hospital, London, UK; 3Observational and Pragmatic Research Institute, Singapore, Singapore; 4Respiratory Research Unit, Bispebjerg University Hospital, Copenhagen, Denmark; 5Al-Rashed Allergy Center, Ministry of Health, Microbiology Department, Faculty of Medicine, Kuwait University, Kuwait, Kuwait; 6AstraZeneca, Gaithersburg, MD, USA; 7Department of Respiratory Medicine, Aalborg University Hospital, Aalborg, Denmark; 8UK Severe Asthma Network and National Registry, Queen’s University Belfast, Belfast, Northern Ireland; 9Son Espases University Hospital-IdISBa-Ciberes, Mallorca, Spain; 10The Centre for Lung Health, Vancouver Coastal Health Research Institute, UBC, Vancouver, Canada; 11AstraZeneca, Barcelona, Spain; 12Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark; 13Allergy, Asthma & Clinical Immunology Service, Alfred Health, Melbourne, Australia; 14Public Health and Preventive Medicine, Monash University, Melbourne, Australia; 15UK Severe Asthma Network andNational Registry, Guy’s and St Thomas’ NHS Trust, London, UK; 16School of Immunology & Microbial Sciences, King’s College London, London, UK; 17 2nd Respiratory Medicine Department, National and Kapodistrian University of Athens Medical School, Attikon University Hospital, Athens, Greece; 18Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, USA; 19Directora Centro de Excelencia en Asma y Alergia, Hospital Médica Sur, Ciudad de México, Mexico; 20Pulmonary, Critical Care, Allergy, and Immunologic Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA; 21Department of Respiratory Medicine, Hospital Universitario Lucus Augusti, Lugo, Spain; 22Allergy Clinic, Department of Dermato-Allergology, Gentofte Hospital, Copenhagen, Denmark; 23University Hospital of Aarhus, Aarhus, Denmark; 24University of Leicester, Department of Respiratory Sciences & NIHR Leicester Biomedical Research Centre (Respiratory Theme), Leicester, UK; 25AstraZeneca, Cambridge, UK; 26Department of Respiratory Medicine, Copenhagen University Hospital-Hvidovre, Hvidovre, Denmark; 27Diamantina Institute & PA-Southside Clinical Unit, The University of Queensland, Brisbane, Australia; 28Division of Allergy & Clinical Immunology, Department of Medicine, National Jewish Health, Denver, CO, USA; 29Division of Allergy & Clinical Immunology, Department of Internal Medicine, University of Colorado School of Medicine, Aurora, CO, USA; 30Optimum Patient Care, Cambridge, UK; 31Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UKCorrespondence: David B PriceObservational and Pragmatic Research Institute, 22 Sin Ming Lane, #06 Midview City, Singapore, 573969 Tel +65 3105 1489Email dprice@opri.sgIntroduction: International registries provide opportunities to describe use of biologics for treating severe asthma in current clinical practice. Our aims were to describe real-life global patterns of biologic use (continuation, switches, and discontinuations) for severe asthma, elucidate reasons underlying these patterns, and examine associated patient-level factors.Methods: This was a historical cohort study including adults with severe asthma enrolled into the International Severe Asthma Registry (ISAR; http://isaregistries.org, 2015– 2020) or the CHRONICLE Study (2018– 2020) and treated with a biologic. Eleven countries were included (Bulgaria, Canada, Denmark, Greece, Italy, Japan, Kuwait, South Korea, Spain, UK, and USA). Biologic utilization patterns were defined: 1) continuing initial biologic; 2) stopping biologic treatment; or 3) switching to another biologic. Reasons for discontinuation/switching were recorded and comparisons drawn between groups.Results: A total of 3531 patients were included. Omalizumab was the most common initial biologic in 2015 (88.2%) and benralizumab in 2019 (29.6%). Most patients (79%; 2791/3531) continued their first biologic; 10.2% (356/3531) stopped; 10.8% (384/3531) switched. The most frequent first switch was from omalizumab to an anti–IL-5/5R (49.6%; 187/377). The most common subsequent switch was from one anti–IL-5/5R to another (44.4%; 20/45). Insufficient efficacy and/or adverse effects were the most frequent reasons for stopping/switching. Patients who stopped/switched were more likely to have a higher baseline blood eosinophil count and exacerbation rate, lower lung function, and greater health care resource utilization.Conclusion: The description of real-life patterns of continuing, stopping, or switching biologics enhances our understanding of global biologic use. Prospective studies involving structured switching criteria could ascertain optimal strategies to identify patients who may benefit from switching.Keywords: severe asthma, biologics, prescribing, cohort study, management, international

Trung N Tran,1 Marjan Kerkhof,2 Victoria Carter,3,4 David B Price3– 5 1Global Medicine Development, AstraZeneca, Gaithersburg, MD, USA; 2Mescio Research, Blauwestad, the Netherlands; 3Observational and Pragmatic Research Institute, Singapore; 4Optimum Patient Care, Cambridge, UK; 5Division of Applied Health Sciences, Centre of Academic Primary Care, University of Aberdeen, Aberdeen, UKCorrespondence: Trung N TranGlobal Medicine Development, AstraZeneca, One MedImmune Way, Gaithersburg, MD, 20878, USATel +1-301-398-5406Email trung.tran1@astrazeneca.comPurpose: Eosinophil count elevations are predictive of adverse outcomes in patients with asthma, yet little is known regarding longitudinal eosinophil patterns and their association with clinical outcomes. The goal of this study was to assess associations between longitudinal persistence of eosinophil elevations and both clinical outcomes and health care resource utilization (HCRU).Methods: Data were extracted from 2 databases in the United Kingdom. Patients included were aged ≥ 13 years, had active asthma, and had ≥ 3 blood eosinophil count (BEC) recordings. Patients were categorized by BEC as: never high (all BEC ≤ 300 cells/μL), intermittently high (≥ 1 BEC > 300 cells/μL but < 75% of BEC > 300 cells/μL), or persistently high (≥ 75% of BEC > 300 cells/μL). Asthma exacerbations, asthma control (risk domain, overall, and full), and HCRU were evaluated for 12 months after the last BEC.Results: The study population comprised 148,021 patients. Persistently high, intermittently high, and never high eosinophil patterns were detected in 13.6%, 40.5%, and 45.9% of patients, respectively. Patients with ≥ 1 elevated BEC were at greater risk for severe asthma exacerbations, regardless of whether the elevation was persistent (rate ratio [RR]: 1.28 [95% CI 1.24– 1.33]; P < 0.001) or intermittent (RR: 1.24 [95% CI 1.21– 1.27]; P < 0.001), compared with patients with no eosinophil elevations. Full asthma control was achieved by < 25% of patients across eosinophil pattern groups, and HCRU did not appreciably differ, although patients with persistently high BEC had the shortest hospital stay duration among the groups.Conclusion: These data suggest that elevated blood eosinophils, regardless of persistency, signify increased risk of severe asthma exacerbations.Keywords: asthma control, asthma exacerbation, biomarker, eosinophilia, phenotype, type 2 inflammation

Thanh Tung Tran Huu,1 Huu Dang Tran,2 Thua Nguyen Tran,3 Bui Bao Hoang2 1Hue University of Medicine and Pharmacy, Hue University, Hue City, Vietnam; 2Department of Internal Medicine, Hue University of Medicine and Pharmacy, Hue City, Vietnam; 3Department of General Internal Medicine and Geriatrics, Hue Central Hospital, Hue City, VietnamCorrespondence: Thua Nguyen TranDepartment of General Internal Medicine and Geriatrics, Hue Central Hospital, Hue City, VietnamTel +84903597695Email tranthuanguyen23@gmail.comIntroduction: Clarifying the prevalence of vitamin D deficiency in diabetic patients, and the relationship between vitamin D concentration and insulin resistance, fasting plasma glucose, and HbA1C in patients in Hue City, Vietnam.Methods: A cross-sectional study on 110 diabetic patients examined at Hue Central Hospital and Hue University of Medicine and Pharmacy Hospital. These patients were collected venous blood sampling, and the 25(OH)D test, fasting plasma glucose test, fasting insulin test, HOMA-IR and QUICKI calculation.Results: Vitamin D deficiency and insufficiency prevalence were 51.8%. The average concentration of 25(OH)D (ng/mL) was 30.67 ± 8.55; this concentration in fasting glucose level ≤ 8 mmol/l group and > 8 mmol/l group was 32.08 ± 9.26 and 28.55± 6.91 (p = 0.033); it was 32.95 ± 8.58 and 28.97 ± 8.17 in HOMA-IR ≤ 3.5 and HOMA-IR > 3.5 group, (p = 0.015); in QUICKI ≤ 0.32 group, it was 29.16 ± 8.12; in QUICKI > 0.32 group, it was 32.85 ± 8.76 (p = 0.025). Patients with an ideal exercise level have higher average levels of 25(OH)D (32.11± 8.62 vs 26.83± 7.16, p=0.003). The average levels of 25(OH)D in male patients are higher than in female patients (33.47± 0.08 vs 29.01± 8.43, p=0.008). Vitamin D deficiency and insufficiency prevalence in patients with HOMA-IR ≤ 3.5 and QUICKI > 0.32 were 36.2% and 37.8%, whereas in those with HOMA-IR > 3.5 and QUICKI ≤ 0.32 they were 63.5% and 61.5% (p = 0.007 and 0.02, respectively). 25(OH)D is negative correlation with fasting glucose level and HOMA-IR, with r = − 0.229 and − 0.192, respectively (p = 0.016 and 0.045); 25(OH)D was positively correlated with QUICKI, with r = 0.235, p = 0.008.Conclusion: Patients who have better glucose-related parameters, such as fasting blood sugar, HOMA-IR and QUICKI, have a better vitamin D status. Some blood sugar-related factors, such as exercise level and sex, are related to vitamin D status.Keywords: vitamin D, insulin resistance, diabetes, HbA1C

David B Price,1,2 Frank Trudo,3 Jaco Voorham,1 Xiao Xu,4 Marjan Kerkhof,1 Joanna Ling Zhi Jie,1 Trung N Tran5 1Observational and Pragmatic Research Institute, Singapore, Singapore; 2Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK; 3Medical Affairs, AstraZeneca, Wilmington, DE, USA; 4Global Payer Evidence and Pricing, AstraZeneca, Gaithersburg, MD, USA; 5Medical Evidence and Observational Research, AstraZeneca, Gaithersburg, MD, USA Purpose: Prior work suggests a threshold of four courses/year of systemic corticosteroid (SCS) therapy is associated with adverse consequences. The objective of this study was to investigate the onset of adverse outcomes beginning at SCS initiation in a broad asthma population. Patients and methods: This historical matched cohort study utilized anonymized, longitudinal medical record data (1984–2017) of patients (≥18 years) with active asthma. Matched patients with first SCS prescription (SCS arm) and no SCS exposure (non-SCS arm) were followed until first outcome event. Associations between time-varying exposure measures and onset of 17 SCS-associated adverse outcomes were estimated using Cox proportional hazard regression, adjusting for confounders, in separate models. Results: We matched 24,117 pairs of patients with median record availability before SCS initiation of 9.9 and 8.7 years and median follow-up 7.4 and 6.4 years in SCS and non-SCS arms, respectively. Compared with patients in the non-SCS arm, patients prescribed SCS had significantly increased risk of osteoporosis/osteoporotic fracture (adjusted hazard ratio 3.11; 95% CI 1.87–5.19), pneumonia (2.68; 2.30–3.11), cardio-/cerebrovascular diseases (1.53; 1.36–1.72), cataract (1.50; 1.31–1.73), sleep apnea (1.40; 1.04–1.86), renal impairment (1.36; 1.26–1.47), depression/anxiety (1.31; 1.21–1.41), type 2 diabetes (1.26; 1.15–1.37), and weight gain (1.14; 1.10–1.18). A dose-response relationship for cumulative SCS exposure with most adverse outcomes began at cumulative exposures of 1.0–0–

Trung N Tran,1 Herve Caspard,1 Fabio Magrini21Clinical Development, MedImmune, Gaithersburg, MD, USA; 2Eli Lilly, San Diego, CA, USAAbstract: Summary data on the incidence density (ie, incidence per person-year [PY]) of serious infection, opportunistic infection, and tuberculosis associated with each of the nine biologic therapies currently indicated in rheumatoid arthritis patients are not available. To summarize these data, a systematic review was conducted with searches on PubMed and Embase of literature ranging from January 1998 to November 2011. Incidence density was extracted and reported using the definitions from the respective publications. If the incidence density was not reported, estimation was made using available information. A total of 72 published studies met the inclusion criteria and were reviewed, including 44 clinical trials, open-label extension studies, or meta-analyses, and 28 observational studies. Additional calculation of the incidence density was performed in 12 studies for serious infection and in 13 studies for opportunistic infection or tuberculosis. The incidence of serious infection was consistent across studies and biologic therapies, ranging from 0 to 11/100 PY but mainly clustered from 2 to 6/100 PY. Fewer incidence data were available for opportunistic infection and tuberculosis. The incidence of opportunistic infection and tuberculosis ranged widely, from 0.01 to 3.0/100 PY and 0.01 to 2.6/100 PY, respectively. The data on serious infection may be used to evaluate the public health risk and benefit of biologic treatment. They may also serve as a point of reference for future studies. The limited data on opportunistic infection and the lack of a consistent definition of opportunistic infection invite caution for a benchmark rate for opportunistic infection as a composite category.Keywords: DMARD, biologic, review, safety, infection, adverse event

Thi Nhi Ha Tran,1,&ast; Quoc Thanh Pham,2,&ast; Lien Huong Tran,3 Tuan Anh Vu,4 Minh Tu Nguyen,5 Hung Tien Pham,6 Thanh Tong Le,7 Thi Thu Ha Bui8 1Management Board, Department of Health, Hanoi, Vietnam; 2Center of Digital Health, Hanoi University of Public Health, Hanoi, Vietnam; 3Management Board, Saint Paul Hospital, Hanoi, Vietnam; 4Medicine Department, Agriculture General Hospital, Hanoi, Vietnam; 5Management Board, Phuc Tho hospital, Hanoi, Vietnam; 6Faculty of Clinical Medicine, Hanoi University of Public Health, Hanoi, Vietnam; 7Student, Hanoi University of Public Health, Hanoi, Vietnam; 8Faculty of Social and Behavioral Sciences, Hanoi University of Public Health, Hanoi, Vietnam&ast;These authors contributed equally to this workCorrespondence: Quoc Thanh Pham, Center of Digital health, Hanoi University of Public Health, Hanoi, 100000, Vietnam, Tel +840 978502383, Fax +84 024 62662385, Email pqt@huph.edu.vnIntroduction: Patient safety culture (PSC) is a vital component in ensuring high-quality and safe patient care. Assessment of physicians’ and nurses’ perceptions of existing hospital PSC is the first step to promoting PSC. This paper is aimed to assess physicians’ and nurses’ perceptions of PSC in 5 public general hospitals in Hanoi, Vietnam.Methods: This cross-sectional study surveyed 410 physicians and 824 nurses utilizing the validated Hospital Survey on Patient Safety Culture in an online format.Results: The composite positive physician’s perception of PSC varied from 47.8 to 89.6% with the lowest composite score of patient safety for “staffing” (47.8%) and the highest composite score for “teamwork within units” (89.6%). The composite positive responses for perception among nurses varied from 51.3 to 94.2% with the lowest composite score of patient safety for “staffing” (51.3%) and the highest composite score for “teamwork within units” (94.2%).Conclusion: The mean scores for “supervisor/manager expectations”; “staffing”, “management support for patient safety”, “teamwork across units”, “handoffs and transitions” among nurses were significantly higher than that among physicians (p< 0.05). About two-thirds of physicians and nurses reported no event in the past 12 months (62.8 and 71.7%, respectively). The nurses reported significantly higher patient grades (every good and excellent) than physicians (75% vs 67.1%, p < 0.001). Hospitals could develop and implement intervention programs to improve patient safety, including providing interventions on teamwork and communication, encouraging staff to notify incidents, and avoiding punitive responses.Keywords: patient safety culture, hospital, physicians, nurses