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Anita Lynam,1 Charlotte Curtis,1 Brooklyn Stanley,2,3 Heath Heatley,3 Chloe Worthington,2,3 Emma-Jane Roberts,2,3 Christopher Price,2,3 Victoria Carter,2,3 John Dennis,1 Andrew McGovern,1 David Price2,3 1Momentum Data, Pendragon House, St. Albans, Hertfordshire, UK; 2Optimum Patient Care, Cambridge, UK; 3Observational and Pragmatic Research Institute, SingaporeCorrespondence: Andrew McGovern, Momentum Data, Pendragon House, St. Albans, Hertfordshire, UK, Email andy.mcgovern@momentumdata.co.ukIntroduction: Electronic medical records (EMRs) maintained in primary care in the UK and collected and stored in EMR databases offer a world-leading resource for observational clinical research. We aimed to profile one such database: the Optimum Patient Care Research Database (OPCRD).Methods and Participants: The OPCRD, incepted in 2010, is a growing primary care EMR database collecting data from 992 general practices within the UK. It covers over 16.6 million patients across all four countries within the UK, and is broadly representative of the UK population in terms of age, sex, ethnicity and socio-economic status. Patients have a mean duration of 11.7 years’ follow-up (SD 17.50), with a majority having key summary data from birth to last data entry. Data for the OPCRD are collected incrementally monthly and extracted from all of the major clinical software systems used within the UK and across all four coding systems (Read version 2, Read CTV3, SNOMED DM+D and SNOMED CT codes). Via quality-improvement programmes provided to GP surgeries, the OPCRD also includes patient-reported outcomes from a range of disease-specific validated questionnaires, with over 66,000 patient responses on asthma, COPD, and COVID-19. Further, bespoke data collection is possible by working with GPs to collect new research via patient-reported questionnaires.Findings to Date: The OPCRD has contributed to over 96 peer-reviewed research publications since its inception encompassing a broad range of medical conditions, including COVID-19.Conclusion: The OPCRD represents a unique resource with great potential to support epidemiological research, from retrospective observational studies through to embedded cluster-randomised trials. Advantages of the OPCRD over other EMR databases are its large size, UK-wide geographical coverage, the availability of up-to-date patient data from all major GP software systems, and the unique collection of patient-reported information on respiratory health.Keywords: primary care, electronic health records, medical records, datasets, demography, health outcomes

Giacomo M Bruno,1,2 Maria Chiara Valentino,2 Alessandra Brunetti,3 Sergio Di Matteo,2 Ivan Begovic,2 Edoardo Croce,4 Garifallia Sakellariou,5 Serena Bugatti,6 Pietro Perotti,7 Silvia Vecchio,7 Simona Migliazza,7 Roberto Langella,8 Giorgio L Colombo1,2 1Department of Drug Sciences, Center of Pharmaceuticals Economics and Medical Technologies Evaluation, CEFAT.Unipv - University of Pavia at Centro di Ricerca SAVE Studi, Milano, Italy; 2S.A.V.E. Research Center - Studi Analisi Valutazioni Economiche, Milano, Italy; 3Research and Innovation Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; 4Scientific Direction - IRCCS istituto Ortopedico Galeazzi, Milan, Italy; 5Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy; 6Department of Internal Medicine and Therapeutics, Division of Rheumatology, University of Pavia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; 7U.O.C. Epidemiological Observatory – Health Protection Agency of Pavia (ATS Pavia), Pavia, Italy; 8SIFO Regional Secretariat - Società Italiana di Farmacia Ospedaliera e dei Servizi Farmaceutici delle Aziende Sanitarie, Milano, ItalyCorrespondence: Giacomo M Bruno, Department of Drug Sciences, Center of Pharmaceuticals Economics and Medical Technologies Evaluation, CEFAT.Unipv - University of Pavia at Centro di Ricerca SAVE Studi, Milano, 20149, Italy, Email giacomomatteo.bruno@unipv.itBackground: The current flows of the SSN represent the set of interest whose interconnection alone justifies the current study. These flows can be interconnected with other sources, institutional or otherwise, in order to answer well-defined questions.Objective: The objective of the study is to verify, through the analysis of administrative databases, any differences in the consumption of health resources between biological off-patent originator drugs and biosimilars in real clinical practice, with particular reference to the rheumatology area.Methods: Through the use of assisted databases (BDA) of ATS Pavia we evaluated the differences in terms of consumption of health resources related to the different drugs under analysis. Annual and daily costs were calculated by total patient cost, stratified for different treatments, considering the sum of total costs for the prescriptions of drugs subject to the analysis. Another objective was to evaluate the adherence of the drugs of interest, by utilizing specific indicators (MPR).Results: A total of 145 patients were analyzed. Among enrolled patients, 26.9% of users were treated with a biosimilar drug, while 73.1% with a biologic originator. Adherence is higher if it is considered the population treated with biosimilar drugs (82.1%). Total cost (including drug prescriptions, hospitalizations, outpatient services, tests for any cause) during the observation period of 1 year is 14,274.08. 87.7% of the total is attributable to drugs. Non-hospitalized patients are the least expensive, whether they were treated with biologics or biosimilars.Conclusion: In our sample, biosimilar drugs tend to be underused: the treatment of a patient with a chronic autoimmune disease is a clinical process that involves many health professionals, and a criticality could also derive from the difficult communication between the various professional figures who get involved with the whole patient treatment.Keywords: real world data, biosimilar, rheumatic diseases, PDTA, EULAR recommendations, rheumatoid arthritis

Quentin M Anstee,1,2 Kate Hallsworth,1,2 Niall Lynch,3 Adrien Hauvespre,4 Eid Mansour,5 Sam Kozma,5 Juliana Bottomley,6 Gary Milligan,7 James Piercy,8 Victoria Higgins9 1Translational & Clinical Research Institute, Faculty of Medical Sciences, University of Newcastle, Newcastle Upon Tyne, UK; 2Liver Unit, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; 3Global Value and Access, Gilead Sciences, Hayes, Uxbridge, UK; 4Market Access and Reimbursement, Gilead Sciences, Hayes, Uxbridge, UK; 5Pricing and Market Access (Middle East), Gilead Sciences, Dubai, United Arab Emirates; 6Pricing and Market Access, Gilead Sciences, Hayes, Uxbridge, UK; 7Statistics Department, Adelphi Real World, Bollington, UK; 8Scientific Franchise, Adelphi Real World, Bollington, UK; 9Scientific and NASH Franchise, Adelphi Real World, Bollington, UKCorrespondence: Victoria Higgins, Adelphi Real World, Adelphi Mill, Grimshaw Lane, Bollington, SK10 5JB, UK, Tel +44 1625 577233, Email victoria.higgins@adelphigroup.comObjective: Stratifying disease severity in patients with non-alcoholic steatohepatitis (NASH) is essential for appropriate treatment and long-term management. Liver biopsy is the reference standard for fibrosis severity in NASH, but less invasive methods are used, eg, Fibrosis-4 Index (FIB-4) and vibration-controlled transient elastography (VCTE), for which reference thresholds for no/early fibrosis and advanced fibrosis are available. We compared subjective physician assessment of NASH fibrosis versus reference thresholds to understand classification in a real-world setting.Methods: Data were drawn from Adelphi Real World NASH Disease Specific ProgrammeTM conducted in France, Germany, Italy, Spain and UK in 2018. Physicians (diabetologists, gastroenterologists, hepatologists) completed questionnaires for five consecutive NASH patients presenting for routine care. Physician-stated fibrosis score (PSFS) based on available information was compared with clinically defined reference fibrosis stage (CRFS) determined retrospectively using VCTE and FIB-4 data and eight reference thresholds.Results: One thousand two hundred and eleven patients had VCTE (n = 1115) and/or FIB-4 (n = 524). Depending on thresholds, physicians underestimated severity in 16– 33% (FIB-4) and 27– 50% of patients (VCTE). Using VCTE ≥ 12.2, diabetologists, gastroenterologists and hepatologists underestimated disease severity in 35%, 32%, and 27% of patients, respectively, and overestimated fibrosis in 3%, 4%, and 9%, respectively (p = 0.0083 across specialties). Hepatologists and gastroenterologists had higher liver biopsy rates than diabetologists (52%, 56%, 47%, respectively).Conclusion: PSFS did not consistently align with CRFS in this NASH real-world setting. Underestimation was more common than overestimation, potentially leading to undertreatment of patients with advanced fibrosis. More guidance on interpreting test results when classifying fibrosis is needed, thereby improving management of NASH.Keywords: fibrosis staging, non-alcoholic steatohepatitis, clinically derived reference fibrosis score, physician-stated fibrosis score, real-world evidence

Benjamin Rosen,1 Annemarie L Pelle,1 Nisha A Lakhi1,2 1Department of Surgery, New York Medical College, School of Medicine, Valhalla, New York, USA; 2Department of Trauma Surgery, Richmond University Medical Center, Staten Island, New York, USACorrespondence: Nisha A Lakhi, Department of Obstetrics and Gynecology/Trauma Surgery, Richmond University Medical Center, 355 Bard Avenue, Staten Island, New York, 10310, USA, Tel +1 718-818-1823, Email nlakhi@NYMC.EDUBackground: The COVID-19 pandemic globally impacted trauma facilities and overall healthcare utilization. This study was conducted to characterize the utilization of trauma services at our Level I Trauma Center in New York City during the COVID-19 pandemic compared to the preceding pre-pandemic year.Methods: A retrospective study of patient presenting to our Level 1 Trauma Center in Staten Island, New York. The pre-pandemic data was extracted from March 1st, 2019–February 29th, 2020. The pandemic year was divided into two phases: the initial wave (March 1st–Sept 1st, 2020) and the protracted phase (September 1st, 2020–March 1st, 2021). Patients were identified using ICD-10 coding and data regarding patient factors, mechanism of injury, and service utilization was extracted from the medical record. Statistical analysis was performed using IBM SPSS v.24.Results: A total of 1650 trauma activations registered during the pre-pandemic phase, 691 during the initial wave, and 826 during the protracted phase. Compared to pre-pandemic, the number of Level 1 trauma activations remained unchanged, however mechanisms of injury shifted. Gunshot wounds (2.6% vs 1.2%), motorcycle crash (4.2% vs 2.0%) and blunt force injury caused by an object (strike injuries) (2.7% vs 1.3%) significantly increased during the initial wave (p-value < 0.05). There was a significant decrease in the percentage of both female (2.93% vs 2.33% vs 5.64%, p-value < 0.01) and pediatric (3.30% vs 3.64% vs 12.9%, p-value < 0.001) assault activations during the initial wave and protracted phase when compared to pre-pandemic levels, respectively. No significant changes were observed for self-harm, falls, accidents, burns, sports injuries, stab wounds, autobody collisions, or motor vehicle accident activations.Conclusion: Trauma centers should be prepared for increases in violent trauma. We also emphasize the need to implement strategies to raise public awareness of pediatric and female assault in the domestic setting, particularly during a mandatory stay-at-home policy where underreporting may occur.Keywords: trauma center, COVID-19, mechanism of injury, service utilization

Bewunetu Zewude,1 Getahun Siraw,2 Yesuf Adem3 1Department of Sociology, College of Social Sciences and Humanities, Wolaita Sodo University, Wolaita Sodo, Ethiopia; 2Department of Sociology, College of Social Sciences and Humanities, Dilla University, Dilla, Ethiopia; 3Department of Business Management, Senabor College, Shashemene, EthiopiaCorrespondence: Bewunetu Zewude, Email bewunetuzewude@gmail.comBackground: The purpose of the study was to identify the choice of mode of delivery and the factors associated with such preferences among pregnant women attending antenatal care services in Southern Ethiopia.Methods: Using an institutional-based cross-sectional survey, quantitative data were collected from randomly selected pregnant women in Southern Ethiopia. A semi-structured questionnaire was distributed to pregnant women who had been attending antenatal healthcare services in purposively selected public and private healthcare facilities in Shashemene town. The completed cases were inserted into SPSS version 26 in which both descriptive and inferential statistical techniques were used to analyze the data.Results: It was found that 75.4% of respondents replied that they prefer vaginal delivery while 24.6% had chosen cesarean section. Personal conviction motivated by the need to experience the labor process, the belief in it being a natural method, the perception that it is better for the wellbeing of both the mother and the child, previous experience of delivery by vaginal method, fear or the need to avoid episiotomy, and economic concerns have been mentioned as reasons for the choice of vaginal delivery. Moreover, respondents’ choice of the mode of delivery is significantly associated with religion, age, number of children, pregnancy experience, previous mode of delivery, self-rated social class status, autonomy to decide about mode of delivery, and type of healthcare organization of antenatal care attendance.Conclusion: Although vaginal delivery has remained the most preferred mode of delivery among most pregnant women, about a quarter of pregnant women have reported that they prefer to deliver by cesarean section, a prevalence rate which is higher than the national average, indicating that the choice of cesarean section is still increasing among women.Keywords: cesarean section, mode of delivery, preference, pregnant women, vaginal delivery

Felicitas Wiedemann,1,2 Franz Porzsolt2 1Department of General and Visceral Surgery, Stuttgart, 70176, Germany; 2Institute of Clinical Economics (ICE) e.V., Ulm, 89081, GermanyCorrespondence: Felicitas Wiedemann, Department of General and Visceral Surgery, Diakonie-Klinikum Stuttgart, Markelstraße 44, Stuttgart, Baden-Württemberg, Germany, Tel +491781731296, Email felicitas.wiedemann@gmail.comPurpose: The assessment of health-related quality of life (hrQoL) may need to be reconsidered due to important differences between efficacy (the effect of a treatment under experimental study conditions) and effectiveness (the effect of a treatment under real-world conditions). We presume that most researchers intend to describe effects under real-world conditions when investigating hrQoL as an endpoint. Unfortunately, most studies are designed to confirm two theories: the efficacy of a new intervention under experimental study conditions and the real-world effectiveness of this intervention on hrQoL under non-experimental study conditions. Conflicting information emerges when the outcomes are supposed to describe effects under real-world conditions, but the assessment generates results obtained under experimental conditions. This paper examines the existing conflict between efficacy and effectiveness in a sample of 100 studies investigating hrQoL.Methods: We analysed a sample of freely available publications of clinical studies listed in PubMed between April 2015 and August 2016 which assessed quality of life as an outcome. We assessed the following four characteristics that should differ in studies measuring either efficacy or effectiveness: 1) specification of the study as a randomised controlled trial or not, 2) description of the study design as pragmatic or not, 3) classification of the study as an efficacy or an effectiveness study and 4) number of selected inclusion and exclusion criteria.Results: 91% of the studies assessed hrQoL under experimental conditions (in a randomised controlled trial), but not under real-world conditions. The important difference between efficacy and effectiveness was not described in 60% of the studies. Only 6% of studies classified the study as a pragmatic trial. The difference between inclusion and exclusion criteria was not addressed in any of the investigated studies.Conclusion: The results of the four criteria confirmed our hypothesis that hrQoL studies are conducted mainly as experimental, but not pragmatic, trials indicating that the meaningfulness of the important difference between efficacy and effectiveness requires further discussion.Keywords: pragmatic trial, experimental study conditions, real-world conditions, efficacy, effectiveness, pragmatic.

Pär Stjärne,1 Duc Tung Nguyen,2 Hans Christian Kuhl2 1Department of Otorhinolaryngology, Karolinska Institute, Stockholm, Sweden; 2Global Clinical Sciences, Meda Pharma GmbH & Co. KG (A Mylan Company, Now Viatris), Bad Homburg, GermanyCorrespondence: Pär Stjärne, Karolinska University Hospital, Department of Otorhinolaryngology, Rhinology, Stockholm, 17176, Sweden, Tel +46707250749, Fax +46 8 774 7907, Email par.stjarne@sll.seBackground: Many allergic rhinitis (AR) patients have moderate/severe persistent disease. MP-AzeFlu (Dymista®) comprises intranasal azelastine hydrochloride and fluticasone propionate in a novel formulation delivered in a single device.Objective: This prospective, noninterventional study assessed the effectiveness of MP-AzeFlu (one spray/nostril twice daily; azelastine hydrochloride = 548 μg; fluticasone propionate = 200 μg) on relieving AR symptom severity.Methods: A visual analogue scale (VAS; 0 mm [not at all bothersome] to 100 mm [very bothersome]) was used during a 42-day MP-AzeFlu treatment period by 161 persistent AR (PER) patients in routine clinical practice in Sweden. Patients also assessed their sleep quality.Results: VAS scores decreased from baseline during the treatment period and patients achieved a clinically relevant VAS score cutoff before Day 7, with 89.3% reporting well or partly controlled symptoms on Day 1. VAS score decreased from 61.4 ± 22.4 mm (baseline) to 32.1 ± 24.6 mm on Day 28 and 26.1 ± 24.3 mm on Day 42 (both p < 0.0001), an overall reduction from baseline on Day 42 of 38.1 ± 28.2 mm. The percentage of patients with very good/good sleep quality increased from 3.7%/28.6% on Day 0 to 16.5%/51.5% on Day 42.Conclusion: MP-AzeFlu provides effective, rapid control of PER assessed by VAS in a real-world clinical setting in Sweden. Symptom improvement was observed at Day 1, sustained for 42 days, and associated with improved sleep quality. MP-AzeFlu significantly improved the QoL of the patients and was well tolerated.Keywords: azelastine, Dymista®, effectiveness, fluticasone propionate, MP29-02, MP-AzeFlu, perennial allergic rhinitis, persistent allergic rhinitis, seasonal allergic rhinitis

Bewunetu Zewude,1 Tewodros Habtegiorgis,1 Ashenafi Hizkeal,1 Tamirat Dela,2 Getahun Siraw3 1Department of Sociology, College of Social Sciences and Humanities, Wolaita Sodo University, Wolaita Sodo town, Ethiopia; 2Department of Civics and Ethical Studies, College of Social Sciences and Humanities, Wolaita Sodo University, Wolaita Sodo town, Ethiopia; 3Department of Sociology, College of Social Sciences and Humanities, Dilla University, Dilla town, EthiopiaCorrespondence: Bewunetu Zewude Email bewunetuzewude@gmail.comBackground: We examined the perceptions of healthcare workers about the side-effects of COVID-19 vaccine and the types of side-effects they experienced in the post-vaccination period.Methods: An institutional-based cross-sectional survey research design was used in which a semi-structured questionnaire was distributed to collect quantitative data from healthcare workers in Southern Ethiopia that were selected on the basis of a multi-stage cluster sampling technique. After inserting the completed cases into SPSS software, descriptive statistical techniques, such as frequencies, percentages, charts and inferential statistical tool, particularly binary logistic regression analysis, were used to analyze and present the data.Results: Majority (43.6%) of respondents perceive that COVID-19 vaccine will have muscle pain around the injection site, followed by fever (39.9%), problems of blood clots (37.8%), headache (35.6%), fatigue (33.5%), and aching limbs (16%). And 63.6%) of them reported that they have experienced muscle pain around the injection site after receiving the COVID-19 vaccine, followed by fatigue (42%), headache (37.2%), fever (34.2%), redness around the injection site (21.6%), and swelling around the injection site (17.8%). Moreover, 25% reported that the fear of potential side-effects of COVID-19 vaccine inhibited them from taking the vaccine. Above all, it is found that respondents’ expectation of COVID-19 vaccine to have such serious side-effects is significantly associated to their educational status (OR = 0.229; P < 0.01; 95%C.I.: 0.080– 0.651).Conclusion: While the expectations of most of the healthcare workers regarding the side-effects of the vaccine are parallel to the normal reactions of the vaccine, a significant proportion of the study participants have reported that they perceive COVID-19 vaccine will have life-threatening side-effects. Such fears have also played a role in affecting vaccine uptake. Therefore, the Ministry of Health, and other concerned government bodies should create further awareness on COVID-19 vaccine and related safety issues.Keywords: COVID-19, perception, side-effect, vaccine, healthcare worker

Fikadu Ejeta,1 Diriba Feyisa,1 Oliyad Kebede,1 Temesgen Aferu,1 Jafer Siraj,2 Desalegn Feyissa,3 Emebet Wodajo,3 Alemu Tamiru3 1Department of Pharmaceutics and Social Pharmacy, School of Pharmacy, College of Medicine and Health Sciences, Mizan-Tepi University, Mizan-Aman, Ethiopia; 2Department of Pharmacology and Pharmaceutical Chemistry, School of Pharmacy, College of Medicine and Health Sciences, Mizan-Tepi University, Mizan-Aman, Ethiopia; 3Department of Clinical Pharmacy and Pharmacy Practice, School of Pharmacy, College of Medicine and Health Sciences, Mizan-Tepi University, Mizan-Aman, EthiopiaCorrespondence: Fikadu Ejeta Tel +251910136034Email fikaduejeta@gmail.comObjective: The objectives of this research were to investigate pharmacy professionals’ counseling practices as well as to evaluate pharmacy professionals’ counseling skills and the content of counseling services provided to patients visiting medicine retail outlets.Methods: A facility-based observational cross-sectional study was used to assess medication counseling practice by pharmacy professionals. Data were gathered through an observation and a semi-structured questionnaire. Epi data version 4.0.2 was used to enter data, which was subsequently exported to SPSS version 21.0 for analysis. ANOVA and post hoc statistical analyses were used to investigate the association between independent and dependent variables; and a 0.05 p-value was considered.Results: This study has a total of 105 pharmacy professionals that were included in the analysis. The majority of those who responded were between the ages of 25 and 29. The most common drug information offered by pharmacy staff to patients was frequency of administration (90%), length of therapy (90%), and unit dose dispensed, according to the current study (86%). Pharmacy professionals’ age was significant on components of counseling practice as on mentioning the name of drugs during dispensing the medication (p=0.000), the route of administration (p=0.000), a drug dose (p=0.003), frequency of drug administration (p=0.016), proper medicine storage (p=0.024), type of dosage form (p=0.025), and duration of treatment (p=0.012). In comparison with the other age groups, an age greater than 40 years was significant on components of counseling practice (p=0.001) as a factor associated with penurious counseling practice than the other groups.Conclusion: This study shows that counseling practice is still quite low in comparison to what is expected. Some of the issues that affect counseling include a high patient load, the lack of a private counseling room, a lack of updated drug knowledge, and a lack of experience were factors that influence counseling.Keywords: counselling, counselling practice, medication, pharmacy professionals, Mizan-Aman, Southwest Ethiopia

Mohammed Alshakka1 ,†Najmaddin A H Hatem,2 Wafa Badullah,3 Rabab Alsakaf,4 Ali Rageh,1 Seena Abdulla Yousef,5 Mohamed Izham Mohamed Ibrahim6 1Section of Clinical Pharmacy, Faculty of Pharmacy, Aden University, Aden, Yemen; 2Department of Pharmacy Practice, College of Clinical Pharmacy, Hodeidah University, Alhodeidah, Yemen; 3Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Aden University, Aden, Yemen; 4Department of Post-Marketing Surveillance, National Pharmacovigilance Center, Supreme Board of Drugs and Medical Appliances, Aden, Yemen; 5Department of Community Medicine and Public Health, Faculty of Medicine and Health Sciences, Aden University, Aden, Yemen; 6Department of Clinical Pharmacy and Practice, College of Pharmacy, QU Health, Qatar University, Doha, Qatar†Dr. Mohammed Alshakka passed away on February 11, 2022Correspondence: Najmaddin A H Hatem, Department of Pharmacy Practice, College of Clinical Pharmacy, Hodeidah University, P.O. 3114, Alhodeidah, Yemen, Tel +967 775040472, Email clin.pharm.najmaddin@gmail.comPurpose: The chAdOx1 nCoV-19 vaccine is the first COVID-19 vaccine available in Yemen. Hence, this local-based study was used to identify the type and frequency of short-term side effects following 48 hours of the first shot of the vaccine.Methods: A cross-section of vaccinated participants in Aden were surveyed by telephone. Descriptive statistics were used for statistical analysis.Results: A total of 500 participants were included through convenient sampling. 27% of them were health care providers. Nearly 70% of the respondent experienced side effects. The top three side effects reported were fever (n=276, 55.2%), myalgia (n=270, 54%) and fatigue (n=247, 49.4%). Generally, most participants stated that they experienced the side effects after the first 24 hours of vaccination.Conclusion: Side effects that participants experienced were not different from the literature, indicating a safe profile for the vaccine. Further studies are needed to identify the side effects after the second and third dose of the vaccine. In addition, more studies are required to assess the efficacy of the existing vaccines against new variants.Keywords: COVID 19, vaccine hesitancy, pharmacovigilance, safety, side-effects

Kerry L Hancock,1 Sinthia Bosnic-Anticevich,2– 4 John D Blakey,5,6 Mark Hew,7,8 Li Ping Chung,9 Biljana Cvetkovski,3 Scott Claxton,10 Peter Del Fante,11 Eve Denton,7,8 Joe Doan,12 Kanchanamala Ranasinghe,13,14 Lucy Morgan,15– 17 Anita Sharma,18 Peter K Smith,19 Deb Stewart,20 Philip J Thompson,21– 23 Russell Wiseman,24 John W Upham,25 Kwok Y Yan,26 Victoria Carter,27 Kiranjeet Dhillon,28 Florian Heraud,28 Thao Le,27 Rebecca Vella,28 David Price27– 30 On behalf of the OPCA Improving Asthma outcomes in Australia Research Group1Chandlers Hill Surgery, Happy Valley, SA, 5159, Australia; 2Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, 2006, Australia; 3Woolcock Institute of Medical Research, Glebe, MSW, 2037, Australia; 4Sydney Local Health District, Camperdown, NSW, 2050, Australia; 5Respiratory Medicine, Sir Charles Gairdner Hospital, Hospital Ave, Nedlands, WA, 6009, Australia; 6Curtin University Medical School, Bentley, Western Australia, 6102, Australia; 7Allergy, Asthma & Clinical Immunology, Alfred Health, Melbourne, VIC, 3004, Australia; 8Public Health and Preventive Medicine, Monash University, Victoria, 3800, Australia; 9Fiona Stanley Hospital, 11 Robin Warren Dr, Murdoch, WA, 6150, Australia; 10Genesis Care Sleep and Respiratory, Joondalup, WA, 6027, Australia; 11Hutt Street General Practice, Adelaide, SA, 5000, Australia; 12HealthPlus Medical Centre, Kogarah, NSW, 2217, Australia; 13School of Medicine, Griffith University, Nathan, QLD, Australia; 14Cannon Hill Family Doctors, Cannon Hill, QLD, 4170, Australia; 15Sydney Medical School, University of Sydney, Sydney, NSW, Australia; 16Department of Thoracic Medicine, Concord Hospital, Sydney, NSW, Australia; 17Australian School of Advanced Medicine, Macquarie University, Sydney, NSW, Australia; 18Platinum Medical Centre, Chermside, QLD, 4032, Australia; 19Griffith University, Southport, QLD, Australia; 20Adjunct Lecturer, School of Medicine, University of Tasmania, Churchill Ave, Hobart, TAS, 7005, Australia; 21The Lung Health Clinic, Hollywood Medical Centre, Nedlands, 6009, Australia; 22The University of Western Australia, Perth, Western Australia, 6009, Australia; 23Curtin University, Bentley, Western Australia, 6102, Australia; 24Suncoast Medical Centre, Coolum Beach, QLD, 4573, Australia; 25Diamantina Institute & PA-Southside Clinical Unit, the University of Queensland, Woolloongabba, QLD, 4102, Australia; 26Department of Respiratory Medicine, W, Camperdown, NSW, 2050, Australia; 27Optimum Patient Care, Cambridgeshire, CB24 3BA, UK; 28Optimum Patient Care Australia, Brisbane, QLD, 4000, Australia; 29Observational and Pragmatic Research Institute, Midview City, 573969, Singapore; 30Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, AB25 2ZD, UKCorrespondence: David Price, Optimum Patient Care Australia, 320 Adelaide St, Brisbane, QLD, 4000, Australia, Tel +4 05 764 842, Email dprice@opri.sgIntroduction: Asthma poses a significant burden for the Australian population. Understanding severe exacerbation rates, and steroid-related burden for adults diagnosed with asthma stands to offer insights into how this could be reduced.Methods: Electronic medical records (EMR) and questionnaires from the Optimum Patient Care Research Database Australia (OPCRDA) were utilised retrospectively. OPCRDA is a real-world database with > 800,000 medical records from Australian primary care practices. Outcomes were severe asthma exacerbations in Australian adults, over a 12-month period, stratified by Global Initiative for Asthma (GINA) treatment intensity steps, and steroid associated comorbidities.Results: Of the 7868 adults treated for asthma, 19% experienced at least one severe exacerbation in the last 12-months. Severe exacerbation frequency increased with treatment intensity (≥ 1 severe exacerbation GINA 1 13%; GINA 4 23%; GINA 5a 33% and GINA 5b 28%). Questionnaire participants reported higher rates of severe exacerbations than suggested from their EMR (32% vs 23%) especially in steps 1, 4 and 5. Patients repeatedly exposed to steroids had an increased risk of osteoporosis (OR 1.95, 95% CI 1.43– 2.66) and sleep apnoea (OR 1.78, 95% CI 1.30– 2.46).Conclusion: The Australian population living with GINA 1, 4, 5a and 5b asthma have high severe exacerbation rates and steroid-related burden, especially when compared to other first world countries, with these patients needing alternative strategies or possibly specialist assessment to better manage their condition.Keywords: asthma, exacerbations, oral corticosteroids, adults, Australia

Shashank Joshi,1 Agam Vora,2 K Venugopal,3 Pramod Dadhich,4 Anil Daxini,5 Sagar Bhagat,6 Saiprasad Patil,6 Hanmant Barkate6 1Department of Endocrinology, Joshi Clinic and Lilavati Hospital and Research Centre, Mumbai, India; 2Department of Pulmonology, Vora Clinic, Mumbai, India; 3Department of Pulmonology, Sooriya Hospital, Chennai, India; 4Department of Pulmonology, Dadhich Clinic, Ajmer, India; 5Department of Medicine, Fortis Hospital, Mumbai, India; 6Global Medical Affairs, Glenmark Pharmaceuticals Ltd, Mumbai, IndiaCorrespondence: Sagar Bhagat, Global Medical Affairs, Glenmark Pharmaceuticals Ltd, Mumbai, India, Tel +91 9930553638, Email sagar.bhagat@glenmarkpharma.comBackground: Favipiravir, an RNA-dependent RNA polymerase inhibitor (RdRp), is a broad-spectrum oral antiviral agent approved in India under emergency use authorization, for the treatment of mild-to-moderate coronavirus disease (COVID-19). The present study was planned to evaluate the effectiveness and safety of favipiravir in real-world clinical practice.Materials and Methods: This was a multicentric, retrospective, single-arm study conducted across four centres in India, after obtaining permission from the independent ethics committee. Medical records were analysed to evaluate effectiveness and safety of patients who were prescribed favipiravir.Results: The medical records of a total of 360 patients met the inclusion criteria, with 358 of them available for the final analysis. Males made up 58.46% of the study population. The average age of enrolled patients was 51.80 ± 16.45 years. The most common symptoms were fever, cough, and myalgia-fatigue. The median time to clinical cure and fever relief was five and four days, respectively. The average length of stay in the hospital was six days. In total, 8% of the patients experienced adverse events. Hepatic enzyme elevation, diarrhoea, decreased appetite, headache, fatigue, and giddiness were the common symptoms.Conclusion: In our real-world study, favipiravir was found to have a clinical cure rate of more than 90% in mild-to-moderate COVID-19 patients. This supports the use of favipiravir in the treatment of COVID-19. Favipiravir was well tolerated, with only minimal side effects, which were transient in nature.Keywords: favipiravir, COVID-19, India, antiviral

Konstantinos Kostikas,1 Chin Kook Rhee,2 John R Hurst,3 Piergiuseppe Agostoni,4,5 Hui Cao,6 Robert Fogel,6 Rupert Jones,7 Janwillem WH Kocks,8– 10 Karen Mezzi,1 Simon Wan Yau Ming,8 Ronan Ryan,8 David B Price8,11 1Novartis Pharma AG, Basel, Switzerland; 2Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea; 3UCL Respiratory, University College London, London, UK; 4Centro Cardiologico Monzino, IRCCS, Milan, Italy; 5Department of Clinical Science and Community Health, University of Milan, Milan, Italy; 6Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 7Plymouth University, Faculty of Medicine and Dentistry, Plymouth, UK; 8Observational and Pragmatic Research Institute, Singapore, Singapore; 9General Practitioners Research Institute, Groningen, the Netherlands; 10Groningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen, Groningen, the Netherlands; 11Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UKCorrespondence: David B PriceCentre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Polwarth Building, Foresterhill, Aberdeen AB25 2ZD, UKTel +65 6802 9724Email dprice@opri.sgPurpose: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) often occur concomitantly, presenting diagnostic and therapeutic challenges for clinicians. We examined the characteristics of patients prescribed adequate versus inadequate therapy within 3 months after newly diagnosed comorbid COPD or HF.Patients and Methods: Eligible patients in longitudinal UK electronic medical record databases had pre-existing HF and newly diagnosed COPD (2017 GOLD groups B/C/D) or pre-existing COPD and newly diagnosed HF. Adequate COPD therapy was defined as long-acting bronchodilator(s) with/without inhaled corticosteroid; adequate HF therapy was defined as beta-blocker plus angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker.Results: Of 2439 patients with HF and newly diagnosed COPD (mean 75 years, 61% men), adequate COPD therapy was prescribed for 726 (30%) and inadequate for 1031 (42%); 682 (28%) remained untreated for COPD. Adequate (vs inadequate) COPD therapy was less likely for women (35%) than men (45%), smokers (36%) than ex-/non-smokers (45%), and non-obese (41%) than obese (47%); spirometry was recorded for 57% prescribed adequate versus 35% inadequate COPD therapy. Of 12,587 patients with COPD and newly diagnosed HF (mean 75 years, 60% men), adequate HF therapy was prescribed for 2251 (18%) and inadequate for 5332 (42%); 5004 (40%) remained untreated for HF. Adequate (vs inadequate) HF therapy was less likely for smokers (27%) than ex-/non-smokers (32%) and non-obese (30%) than obese (35%); spirometry was recorded for 65% prescribed adequate versus 39% inadequate HF therapy.Conclusion: Many patients with comorbid COPD/HF receive inadequate therapy after new diagnosis. Improved equity of access to integrated care is needed for all patient subgroups.Keywords: beta-blocker, long-acting bronchodilator, integrated care, multimorbidity

Lisa M Hess,1 Michael Grabner,2 Liya Wang,2 Astra M Liepa,1 Xiaohong Ivy Li,3 Zhanglin Lin Cui,3 Lee Bowman,1 William R Schelman4 1Global Patient Outcomes, Eli Lilly and Company, Indianapolis, IN, USA; 2Life Sciences Research, HealthCore Inc., Wilmington, DE, USA; 3Global Statistics, Eli Lilly and Company, Indianapolis, IN, USA; 4Medical Affairs, Eli Lilly and Company, Indianapolis, IN, USACorrespondence: Lisa M HessEli Lilly and Company, Indianapolis, IN 46285, USAEmail Hess_lisa_m@lilly.comBackground: As real-world data resources expand and improve, there will increasingly be opportunities to study the effectiveness of interventions. There is a need to ensure that study designs explore potential sources of bias and either acknowledge or mitigate them, in order to improve the accuracy of findings. The objective of this study was to understand newly approved drug utilization patterns in real-world clinical settings over time.Methods: This retrospective study included three sources of real-world data (claims, electronic health records, and recoded data from a quality care program) collected from patients diagnosed with gastric cancer who initiated therapy with either trastuzumab or ramucirumab. Linear regression was used to investigate trends in the use of these drugs for the care of patients with gastric cancer over time from Food and Drug Administration (FDA) approval.Results: Eligible patients (n=1700) had consistent demographic and clinical characteristics over time. After regulatory approval, trastuzumab was used in later lines of therapy and then shifted to earlier lines (p=0.002), while ramucirumab utilization remained consistent over time after FDA approval (p=0.49). Ramucirumab augmentation, defined as the addition of the drug after initiation of a line of therapy, decreased over time (p=0.03), and trastuzumab augmentation remained consistent over time (p=0.58).Conclusion: Since treatment effectiveness may change across lines of treatment, bias may arise if there are changes in the use of the drug (such as line migration) during the time period of analysis using real-world data.Keywords: gastric cancer, trastuzumab, ramucirumab, bias, real-world data

Hannah R Whittaker,1 Steven J Kiddle,2 Jennifer K Quint1 1National Heart and Lung Institute, Imperial College London, London, UK; 2MRC Biostatistics Unit, University of Cambridge, Cambridge, UKCorrespondence: Hannah R Whittaker Email h.whittaker@imperial.ac.ukBackground: Electronic healthcare records (EHR) are increasingly used in epidemiological studies but are often viewed as lacking quality compared to randomised control trials and prospective cohorts. Studies of patients with chronic obstructive pulmonary disease (COPD) often use the rate of forced expiratory volume in 1 second (FEV1) decline as an outcome; however, its definition and robustness in EHR have not been investigated. We aimed to investigate how the rate of FEV1 decline differs by the criteria used in an EHR database.Methods: Clinical Practice Research Datalink and Hospital Episode Statistics were used. Patient populations were defined using 8 sets of criteria around repeated FEV1 measurements. At a minimum, patients had a diagnosis of COPD, were ≥ 35 years old, were current or ex-smokers, and had data recorded from 2004. FEV1 measurements recorded during follow-up were identified. Thereafter, eight populations were defined based on criteria around: i) the exclusion of patients or individual measurements with potential measurement error; ii) minimum number of FEV1 measurements; iii) minimum time interval between measurements; iv) specific timing of measurements; v) minimum follow-up time; and vi) the use of linked data. For each population, the rate of FEV1 decline was estimated using mixed linear regression.Results: For 7/8 patient populations, rates of FEV1 decline (age and sex adjusted) were similar and ranged from − 18.7mL/year (95% CI − 19.2 to − 18.2) to − 16.5mL/year (95% CI − 17.3 to − 15.7). Rates of FEV1 decline in populations that excluded patients with potential measurement error ranged from − 79.4mL/year (95% CI − 80.7 to − 78.2) to − 46.8mL/year (95% CI − 47.6 to − 46.0).Conclusion: FEV1 decline remained similar in a COPD population regardless of number of FEV1 measurements, time intervals between measurements, follow-up period, exclusion of specific FEV1 measurements, and linkage to HES. However, exclusion of individuals with questionable data led to selection bias and faster rates of decline.Keywords: electronic healthcare records, spirometry, COPD, lung function

Chester Fox,1,2 Wilson Pace,1,3 Elias Brandt,1 Victoria Carter,4,5 Ku-Lang Chang,6 Chelsea Edwards,7 Alexander Evans,4 Gabriela Gaona,1 MeiLan K Han,8 Alan Kaplan,5,9,10 Rachel Kent,1 Janwillem WH Kocks,5,11– 13 Maja Kruszyk,5,7 Le Lievre Chantal,5,7 Tessa LiVoti,4,5 Cathy Mahle,14 Barry Make,15 Amanda Ratigan,1 Asif Shaikh,14 Neil Skolnik,16,17 Brooklyn Stanley,4 Barbara P Yawn,17 David B Price4,5,18 1DARTNet Institute, Aurora, CO, USA; 2University at Buffalo, Buffalo, NY, USA; 3University of Colorado, Denver, CO, USA; 4Optimum Patient Care, Cambridge, UK; 5Observational and Pragmatic Research Institute, Singapore; 6University of Florida College of Medicine, Gainesville, FL, USA; 7Optimum Patient Care, Brisbane, Queensland, Australia; 8University of Michigan, Ann Arbor, MI, USA; 9Family Physician Airways Group of Canada, Stouffville, Ontario, Canada; 10University of Toronto, Toronto, Canada; 11General Practitioners Research Institute, Groningen, the Netherlands; 12Groningen Research Institute Asthma and COPD (GRIAC), University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; 13Department of Pulmonology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; 14Boehringer Ingelheim, Ridgefield, CT, USA; 15Department of Medicine, NJH, Denver, CO, USA; 16Abington Jefferson Health, Jenkintown, PA, USA; 17University of Minnesota, Minneapolis, MN, USA; 18Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UKCorrespondence: 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.sgIntroduction: Little is known about the variability in chronic obstructive pulmonary disease (COPD) management and how it may be affected by patient characteristics across different healthcare systems in the US. This study aims to describe demographic and clinical characteristics of people with COPD and compare management across five primary care medical groups in the US.Methods: This is a retrospective observational registry study utilizing electronic health records stored in the Advancing the Patient Experience (APEX) COPD registry. The APEX registry contains data from five US healthcare organizations located in Texas, Ohio, Colorado, New York, and North Carolina. Data on demographic and clinical characteristics of primary care patients with COPD between December 2019 and January 2020 were extracted and compared.Results: A total of 17,192 patients with COPD were included in analysis: Texas (n = 811), Ohio (n = 8722), Colorado (n = 472), New York (n = 1149) and North Carolina (n = 6038). The majority of patients at each location were female (> 54%) and overweight/obese (> 60%). Inter-location variabilities were noted in terms of age, race/ethnicity, exacerbation frequency, treatment pattern, and prevalence of comorbid conditions. Patients from the Colorado site experienced the lowest number of exacerbations per year while those from the New York site reported the highest number. Hypertension was the most common co-morbidity at 4 of 5 sites with the highest prevalence in New York. Depression was the most common co-morbidity in Ohio. Treatment patterns also varied by site; Colorado had the highest proportion of patients not on any treatment. ICS/LABA was the most commonly prescribed treatment except in Ohio, where ICS/LABA/LAMA was most common.Conclusions and Relevance: Our data show heterogeneity in demographic, clinical, and treatment characteristics of patients diagnosed with COPD who are managed in primary care across different healthcare organizations in the US.Keywords: quality of care, observational study, research database, patient-reported outcomes

Rupert Jones,1– 3 Andrew Davis,1,2 Brooklyn Stanley,1,2 Steven Julious,4 Dermot Ryan,5 David J Jackson,6 David MG Halpin,7 Katherine Hickman,8 Hilary Pinnock,9 Jennifer K Quint,10 Kamlesh Khunti,11 Liam G Heaney,12 Phillip Oliver,4 Salman Siddiqui,13 Ian Pavord,14 David HM Jones,15 Michael Hyland,3,16 Lewis Ritchie,17 Pam Young,18 Tony Megaw,18 Steve Davis,19 Samantha Walker,20 Stephen Holgate,21 Sue Beecroft,22 Anu Kemppinen,1,2 Francis Appiagyei,1,2 Emma-Jane Roberts,1,2 Megan Preston,1,2 Antony Hardjojo,1,2 Victoria Carter,1,2 Marije van Melle,1,2 David Price1,2,17 1Optimum Patient Care, Cambridge, UK; 2Observational and Pragmatic Research Institute, Singapore, Singapore; 3Faculty of Health, University of Plymouth, Plymouth, UK; 4University of Sheffield, South Yorkshire, UK; 5Usher Institute, University of Edinburgh, Edinburgh, UK; 6Guy’s & St Thomas’ NHS Trust, School of Immunology & Microbial Sciences, King’s College London, London, UK; 7University of Exeter Medical School, College of Medicine and Health, University of Exeter, Exeter, UK; 8Bradford and Leeds Clinical Commissioning Group, Leeds, UK; 9Asthma UK Centre for Applied Research, Usher Institute, The University of Edinburgh, Edinburgh, UK; 10National Heart & Lung Institute, Imperial College London, London, UK; 11Diabetes Research Centre, University of Leicester, Leicester, UK; 12Wellcome-Wolfson Centre for Experimental Medicine, Queen’s University Belfast, Belfast, Northern Ireland; 13Institute for Lung Health, Leicester National Institute for Health Research Biomedical Research Centre, University of Leicester, Leicester, UK; 14Respiratory Medicine Unit and Oxford Respiratory NIHR BRC, Nuffield Department of Medicine, University of Oxford, Oxford, UK; 15Box Surgery, Wiltshire, UK; 16Plymouth Marjon University, Plymouth, UK; 17Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK; 18Wellbeing Software, Mansfield, UK; 19Interface Clinical Services, Leeds, UK; 20Asthma UK & British Lung Foundation, London, UK; 21Clinical and Experimental Sciences, University of Southampton, Southampton, UK; 22OPEN Health, Buckinghamshire, UKCorrespondence: David PriceAcademic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Polwarth Building, Foresterhill, Aberdeen, AB25 2ZD, UKTel +65 3105 1489Email dprice@opri.sgIntroduction: Symptoms may persist after the initial phases of COVID-19 infection, a phenomenon termed long COVID. Current knowledge on long COVID has been mostly derived from test-confirmed and hospitalized COVID-19 patients. Data are required on the burden and predictors of long COVID in a broader patient group, which includes both tested and untested COVID-19 patients in primary care.Methods: This is an observational study using data from Platform C19, a quality improvement program-derived research database linking primary care electronic health record data (EHR) with patient-reported questionnaire information. Participating general practices invited consenting patients aged 18– 85 to complete an online questionnaire since 7th August 2020. COVID-19 self-diagnosis, clinician-diagnosis, testing, and the presence and duration of symptoms were assessed via the questionnaire. Patients were considered present with long COVID if they reported symptoms lasting ≥ 4 weeks. EHR and questionnaire data up till 22nd January 2021 were extracted for analysis. Multivariable regression analyses were conducted comparing demographics, clinical characteristics, and presence of symptoms between patients with long COVID and patients with shorter symptom duration.Results: Long COVID was present in 310/3151 (9.8%) patients with self-diagnosed, clinician-diagnosed, or test-confirmed COVID-19. Only 106/310 (34.2%) long COVID patients had test-confirmed COVID-19. Risk predictors of long COVID were age ≥ 40 years (adjusted Odds Ratio [AdjOR]=1.49 [1.05– 2.17]), female sex (adjOR=1.37 [1.02– 1.85]), frailty (adjOR=2.39 [1.29– 4.27]), visit to A&E (adjOR=4.28 [2.31– 7.78]), and hospital admission for COVID-19 symptoms (adjOR=3.22 [1.77– 5.79]). Aches and pain (adjOR=1.70 [1.21– 2.39]), appetite loss (adjOR=3.15 [1.78– 5.92]), confusion and disorientation (adjOR=2.17 [1.57– 2.99]), diarrhea (adjOR=1.4 [1.03– 1.89]), and persistent dry cough (adjOR=2.77 [1.94– 3.98]) were symptom features statistically more common in long COVID.Conclusion: This study reports the factors and symptom features predicting long COVID in a broad primary care population, including both test-confirmed and the previously missed group of COVID-19 patients.Keywords: SARS-CoV-2, questionnaire, observational study, frailty, chronic diseases

Keiji Hirai, Hiroaki Nonaka, Moeka Ueda, Junki Morino, Shohei Kaneko, Saori Minato, Yuko Mutsuyoshi, Katsunori Yanai, Hiroki Ishii, Momoko Matsuyama, Taisuke Kitano, Akinori Aomatsu, Haruhisa Miyazawa, Kiyonori Ito, Yuichiro Ueda, Susumu Ookawara, Yoshiyuki Morishita Division of Nephrology, First Department of Integrated Medicine, Saitama Medical Center, Jichi Medical University, Saitama, JapanCorrespondence: Keiji HiraiDivision of Nephrology, First Department of Integrated Medicine, Saitama Medical Center, Jichi Medical University, Saitama, JapanTel +81-48-647-2111Fax +81-48-647-6831Email keijihirai@kfy.biglobe.ne.jpPurpose: We compared the efficacy of teneligliptin versus linagliptin for glycemic control and renoprotection in patients with advanced-stage diabetic kidney disease.Patients and Methods: Changes in the glycated hemoglobin (HbA1c), fasting blood glucose concentration, urine albumin-to-creatinine ratio (UACR), and estimated glomerular filtration rate (eGFR) during a 12-month period were retrospectively analyzed after switching from linagliptin to teneligliptin in 13 patients with advanced-stage diabetic kidney disease (teneligliptin group). Thirteen propensity score-matched patients who were treated with linagliptin alone served as controls (linagliptin group).Results: The HbA1c, fasting blood glucose concentration, and UACR did not change during the 12-month study period in either group. The annual change rate in the eGFR did not differ between before and after baseline in either group.Conclusion: Switching from linagliptin to teneligliptin may not improve glycemic control, reduce urinary protein excretion, or ameliorate the rate of renal function decline in patients with advanced-stage diabetic kidney disease. These results suggest that teneligliptin may not be more advantageous for glycemic control and renoprotection compared with linagliptin in patients with advanced-stage diabetic kidney disease.Keywords: chronic kidney disease, diabetic kidney disease, teneligliptin, linagliptin

Solomon Tesfaye,1 Niguse Hamba,1 Wakjira Kebede,2 Mitiku Bajiro,3 Lemessa Debela,1 Tihahun Alemayehu Nigatu,1 Asfaw Gerbi1 1Anatomy Unit, Department of Biomedical Sciences, Faculty of Medical Sciences, Institute of Health, Jimma University, Jimma, Ethiopia; 2Immunology Unit, School of Medical Laboratory Sciences, Faculty of Health Sciences, Institute of Health, Jimma University, Jimma, Ethiopia; 3Parasitology Unit, School of Medical Laboratory Sciences, Faculty of Health Sciences, Institute of Health, Jimma University, Jimma, EthiopiaCorrespondence: Solomon TesfayeAnatomy Unit, Department of Biomedical Sciences, Faculty of Medical Sciences, Institute of Health, Jimma University, Jimma, EthiopiaTel +251911939324Email sole.tesfaye2010@gmail.comBackground: Human anatomy has historically been a cornerstone in medical education and is special in that it uses human remains kept in various anatomical facilities like a morgue, gross anatomy laboratory, or museums for instruction and research. While serving knowledge advancement facilitating clinical practice and research, human cadaver handling, and usage at all levels, such as cadaver sourcing, transportation, storage, preservation, dissection, and final disposal deserves in return the utmost respect. In Ethiopia, even though there is not enough information on when, where, and by whom the first cadaver dissection was conducted, dissection is being conducted in many of its medical schools. Despite ethical necessity surrounding human body usage in every anatomical setting, there is still ethical and legal uncertainty due to several challenging barriers which is severe in developing nations including Ethiopia. The aim of this study is, therefore, to assess ethical practices of handling and usage of the human body to promote, in the near future, formulation and implementation of acceptable, respectful, and ethical guidelines for the anatomy dissection laboratories and related settings in Ethiopia.Methods: A multicentered cross-sectional study was used at selected anatomy facilities of eight Ethiopian medical schools. The collected data through structured questionnaires and checklists were cleaned, preset and entered in to SPSS version 20 for analysis. Internal consistency and reliability were measured by using Cronbach’s alpha.Results: The study result showed vivid human body ethical breaches that ranged from lack of power by anatomy unit to oversee the process during sourcing, transportation, embalming, caring, and dissection of cadavers in the anatomy laboratories to student’s mistreatment of cadavers.Conclusion: In addition to lack of compliance due to lack of standard ethical guidelines or policies regarding human body usage, the compliance-based professional development is also nonexistent. The ethical way of body sourcing is through body donation; however, in Ethiopia, anatomy teaching exclusively depends on unclaimed bodies. Using a body for dissection that is solely sourced unethically may generate a negative emotional sense of life for anatomy instructors, technical assistants, morticians, and medical students. We inspire better provision of moral and ethical exercise with the good practice concerning the human body through recognizing the humanity and uniqueness of the deceased person. The results of this study serve as a serious condemnation of practices in Ethiopian anatomy facilities and we urge the Anatomical Society of Ethiopia to play its part in changing the present practices related to ethical and legal uncertainty of the human body usage.Keywords: human body, ethical compliance, anatomical facilities, Ethiopian medical schools

Carolyn Martin,1 Eleena Koep,1 John White,1 Angela Belland,1 Heidi Waters,2 Felicia Forma3 1Optum, Eden Prairie, MN, USA; 2Policy Research Health Outcomes, Otsuka Pharmaceutical Development & Commercialization, Inc, Princeton, NJ, USA; 3Otsuka Pharmaceutical Development & Commercialization, Inc., Health Economics and Outcomes Research, Princeton, NJ, USACorrespondence: Carolyn MartinOptum, 11000 Optum Circle, Eden Prairie, MN, 55344, USATel +1 952-205-7716Fax +1 877 503 7362Email carolyn.martin@optum.comIntroduction: Successful treatment for serious mental illnesses (SMIs) requires a good therapeutic alliance with healthcare providers and compliance with prescribed therapies such as antipsychotic medications. This retrospective study, which utilized administrative claims linked with abstracted medical chart data, addressed a data gap regarding compliance-related discussions between providers and patients.Methods: Commercially insured patients in ambulatory care post-acute (emergency or inpatient) event were eligible. Criteria included age 18– 65 years; schizophrenia, bipolar disorder, or major depressive disorder diagnoses; continuous enrollment 6 months before to 12 months after the first acute event claim dated 01/01/2014 to 12/31/2015; and antipsychotic medication prescription. Demographic and clinical data, and patient–provider discussions about treatment compliance were characterized from claims and abstracted medical charts.Results: Ninety patients (62% female, mean age 41 years) were included and 680 visits were abstracted; only 58% had first-visit antipsychotic compliance discussions. Notably, 18% of patients had discussions using the specific terms “compliance,” “persistence,” or “adherence,” whereas half were identified by more general terms. Compliance discussions were observed least often among the patients with schizophrenia, as comparedwith bipolar or major depressive disorders—a counterintuitive finding.Discussion: Compliance discussions may represent intervention opportunities to optimize treatment, yet their study is a complex endeavor. The results of this study show an opportunity to improve this valuable treatment step.Keywords: schizophrenia, bipolar disorder, major depression disorder, medication compliance, antipsychotic medication

Bewunetu Zewude, Tewodros Habtegiorgis Department of Sociology, Wolaita Sodo University, Wolaita Sodo Town, EthiopiaCorrespondence: Bewunetu Zewude Tel +251917104277Email bewunetuzewude@gmail.comBackground: Acceptance of a vaccine or hesitancy towards it have great public health implications as they partly determine the extent to which people are exposed to infections that could have otherwise been prevented. The present study examined the willingness of primary and secondary school teachers, bank employees, and university instructors in southern Ethiopia to take a Covid-19 vaccine and the factors associated with their willingness.Methods: An institutional-based cross-sectional study design was used with a quantitative research approach. Primary data were gathered mainly through the use of a survey research method in which a self-administered questionnaire was distributed to randomly selected research participants in Wolaita Sodo town. Data analysis was conducted using statistical techniques, including percentages, frequency distributions, and logistic regression analysis.Results: Research participants generally had a low (46.1%) willingness to take a COVID-19 vaccine. The main reason for most (37%) respondents’ hesitancy to take the vaccine is found to be the concern over the safety and/or the side effects of the vaccine (37%), followed by doubt about the vaccine’s effectiveness (20.7%), and lack of adequate information (12.7%). Moreover, 38.9% of survey participants revealed that they would like to take a COVID-19 vaccine other than AstraZeneca whereas 61.1% of respondents replied that they do not want to take any kind of COVID-19 vaccine. Furthermore, respondents’ willingness to take a COVID-19 vaccine is significantly associated with attitude towards the vaccine (OR = 2.830; 95% CI = 1.834– 4.368), belief that Covid-19 exists in the study area (OR = 0.221; 95% CI = 0.083– 0.589), the perception that prevalence and death rate reports of the government are real (OR = 0.365; 95% CI = 0.197– 0.676), status of chronic diseases (OR = 2.883; 95%CI = 1.039– 7.999), and having a close relative/friend ever infected by COVID-19 (OR = 2.602; 95% CI = 1.117– 6.063).Conclusion: The findings of the research demonstrated that there is generally low willingness to take a COVID-19 vaccine among university instructors, bank employees, and primary and secondary school teachers in southern Ethiopia. Therefore, the federal ministry of health, Ethiopian food and drug controlling agency, the media, and all other concerned organizations should create increased awareness about the safety/side effects issues and the need to take the vaccine.Keywords: Covid-19, hesitancy, safety, willingness, vaccine

David Price,1,2 Rupert Jones,3 Pascal Pfister,4 Hui Cao,5 Victoria Carter,6 Anu Kemppinen,6 Björn Holzhauer,4 Alan Kaplan,7 Allan Clark,8 David MG Halpin,9 Hilary Pinnock,10 James D Chalmers,11 Job FM van Boven,12 Kai M Beeh,13 Konstantinos Kostikas,14 Nicolas Roche,15 Omar Usmani,16 Paul Mastoridis5 1Observational and Pragmatic Research Institute, Singapore, Singapore; 2Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK; 3Faculty of Health, University of Plymouth, Plymouth, Devon, UK; 4Novartis Pharma AG, Basel, Switzerland; 5Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 6Observational and Pragmatic Research International Ltd, Stubbs House Stubbs Green, London, Norwich, UK; 7Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada; 8Norwich Medical School, University of East Anglia, Norwich, UK; 9University of Exeter Medical School, College of Medicine and Health, University of Exeter, Exeter, UK; 10Allergy and Respiratory Research Group, Usher Institute, University of Edinburgh, Edinburgh, UK; 11College of Medicine, University of Dundee, Dundee, UK; 12Department of Clinical Pharmacy & Pharmacology, Groningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; 13Clinical Research, Insaf Respiratory Research Institute, Wiesbaden, Germany; 14Respiratory Medicine Department, University of Ioannina School of Medicine, Ioannina, Greece; 15Cochin Hospital and Institute, APHP Centre, University of Paris, Paris, France; 16National Heart & Lung Institute (NHLI), Imperial College London and Royal Brompton Hospital, London, UKCorrespondence: David PriceCentre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Polwarth Building, Foresterhill, Aberdeen, AB25 2ZD, UKTel +44 65 6962 3627Email dprice@opri.sgBackground: Poor treatment adherence in COPD patients is associated with poor clinical outcomes and increased healthcare burden. Personalized approaches for adherence management, supported with technology-based interventions, may offer benefits to patients and providers but are currently unproven in terms of clinical outcomes as opposed to adherence outcomes.Methods: Maximizing Adherence and Gaining New Information For Your COPD (MAGNIFY COPD study), a pragmatic cluster randomized trial, aims to evaluate the impact of an adherence technology package (interventional package), comprising an adherence review, ongoing provision of a dual bronchodilator but with an add-on inhaler sensor device and a connected mobile application. This will compare time to treatment failure and other clinical outcomes in patients identified at high risk of exacerbations with historic poor treatment adherence as measured by prescription collection to mono/dual therapy over one year (1312 patients) versus usual care. Treatment failure is defined as the first occurrence of one of the following: (1) moderate/severe COPD exacerbation, (2) prescription of triple therapy (inhaled corticosteroid/long-acting β2-agonist/long-acting muscarinic antagonist [ICS/LABA/LAMA]), (3) prescription of additional chronic therapy for COPD, or (4) respiratory-related death. Adherence, moderate/severe exacerbations, respiratory-related healthcare resource utilization and costs, and intervention package acceptance rate will also be assessed. Eligible primary care practices (N=176) participating in the Optimum Patient Care Quality Improvement Program will be randomized (1:1) to either adherence support cluster arm (suitable patients already receiving or initiated Ultibro® Breezhaler® [indacaterol/glycopyrronium] will be offered interventional package) or the control cluster arm (suitable patients continue to receive usual clinical care). Patients will be identified and outcomes collected from anonymized electronic medical records within the Optimum Patient Care Research Database. On study completion, electronic medical record data will be re-extracted to analyze outcomes in both study groups.Registration Number: ISRCTN10567920.Conclusion: MAGNIFY will explore patient benefits of technology-based interventions for electronic adherence monitoring.Keywords: adherence monitoring, applications, chronic obstructive pulmonary disease, medication adherence, pragmatic randomized clinical trial, technology

María Carolina Kamel Escalante,1 Abbas Abdennour,2 Antoine Farah,3 Ernesto Rivera-Richardson,4 Fernando Burgos,5 Ilenia Forero,6 Margarita Murrieta-Aguttes,7 Mohamed El Laboudy,8 Ndeye Ramatoulaye Diagne-Gueye,9 Sergio Barragan Padilla10On behalf of DIRECT Study Group1Department of Pediatrics, Hospital General del IVSS Dr Miguel Perez Carreno, Caracas, Venezuela; 2Department of Pediatrics, Santé Publique Baraki, Algiers, Algeria; 3Department of Pediatrics, Saint-Georges Hospital, Ajaltoun, Lebanon; 4Department of Pediatrics, Clinica Particular Paseo General, San Salvador, El Salvador; 5Maternal and Child Department, Hospital Universitario Austral, Buenos Aires, Argentina; 6Centro de Diagnostico Pediatrico, Panama, Panama; 7Consumer Healthcare Division, Sanofi-Aventis Group, Gentilly, France; 8Faculty of Medicine, Ain Shams University, Kalyoubya, Egypt; 9Albert Royer Children’s Hospital, Dakar, Senegal; 10ISSSTE Lopez Mateos Hospital, Department of Pediatrics, México, DF, MexicoObjective: To evaluate the daily practice of pediatricians, physician-perceived reasons for unsatisfactory effects of treatment, and unmet needs in the management of acute pain and/or fever.Methods: This was a multinational (n=13), multicenter, non interventional, cross-sectional study conducted in Latin America, Africa, and the Middle East in children under 16 years of age with fever (defined as a central body temperature ≥38°C) and/or acute pain (defined as pain lasting ≤6 weeks). Data were collected during a single visit using a structured physician-administered questionnaire and case report forms.Results: A total of 2125 patients were recruited by 178 physicians between September 2010 and September 2011. From the 2117 analyzed patients, 1856 (87.7%) had fever, 705 (33.3%) had acute pain, and 446 (21.1%) had both. Of 1843 analyzed patients with fever, 1516 (82.3%) were previously prescribed a pharmacological treatment for the management of fever concomitantly with a non pharmacological approach, while 1817/1856 patients (97.9%) were currently receiving a prescribed pharmacological treatment for fever. Paracetamol/acetaminophen was the most commonly prescribed antipyretic medication during both previous (70.8%) and current (64.1%) consultations. With regard to acute pain management, 67.2% of the patients received previous and 93.9% received current treatment for pain. The most frequently prescribed analgesic during previous consultations was paracetamol/acetaminophen (53.7%), and the current most commonly prescribed analgesics were non steroidal anti-inflammatory drugs (55.2%). Treatment patterns for patients with both fever and acute pain were similar. Overall, 53.4% of the physicians reported poor treatment compliance as a reason for the unsatisfactory effect of the pain/fever treatment, and the most common unmet need was the availability of new drugs (according to 63.5% of the physicians).Conclusions: Adequate management of fever was observed; however, due to the complex etiology of pediatric pain, better evaluation and management of pain in pediatrics is necessary.Keywords: acute pain, fever, non-steroidal anti-inflammatory drugs, paracetamol/acetaminophen, disease management, physician’s perception

Sean Mccafferty,1 Sean Ashley2 1Department of Ophthalmology, College of Medicine, University of Arizona, Tucson, AZ, USA; 2College of Optical Sciences, University of Arizona, Tucson, AZ, USACorrespondence: Sean Mccafferty 6422 E. Speedway Blvd, Tucson, AZ 85710, USATel +1 (520) 327-3487Email sjmccafferty66@hotmail.comPurpose: Evaluate the correlation between statutory social distancing interventions and Covid-19 mortality independently in both the United States and Europe. The study is presented as a potential methodology to evaluate the effectiveness of statutory social distancing policy.Patients and Methods: Twenty-seven states in the United States and, separately, 12 European countries were selected which had clearly defined and dated establishment of statewide or national mandates for social distancing measures from the Institute for Health Metrics and Evaluation (IHME) data. Mandated social distancing measures considered in this study include: School closures, Prohibition on mass gatherings, business closures, stay at home orders, severe travel restrictions, and closure of non-essential businesses. The state/country Covid-19 peak mortality rate (PMR) was defined as the initial averaged normalized maximum during which social distancing mandates were in effect. Mandate-days were defined as the total days legislative mandates were in place to the PMR.Results: The normalized peak mortality rate in the US and in Europe did not demonstrate a statistically significant correlation to the total mandate days (R-squared=0.053, p=0.246, R-squared=2.4E-06, p=0.996). A significant correlation was found between normalized mortality rate and state/country population density (R-squared=0.524, p=0.00002,R-squared=0.397, p=0.0281).Discussion: The analysis appears to suggest no mandate effective reduction in Covid-19 mortality rate to its defined initial peak when interpreting their mean-effect. A strong correlation to population density suggests human interaction frequency does affect the peak mortality rate.Keywords: epidemiology, analysis, SARS-Cov-2, mortality-rate, social-distancing, orders

Linah M Ashy Department of Oral and Maxillofacial Prosthodontics, King Abdulaziz University Faculty of Dentistry (KAUFD), Jeddah, Saudi ArabiaCorrespondence: Linah M AshyDepartment of Oral and Maxillofacial Prosthodontics, King Abdulaziz University Faculty of Dentistry, P.O.Box 80209, Jeddah, 21589, Saudi ArabiaTel +966 505679991Email lashy@kau.edu.saPurpose: To investigate the attitude of clinicians in Saudi Arabia towards dental implant treatment using different implant surgery approaches.Materials and Methods: This cross-sectional observational study was conducted using a web-based questionnaire wherein 56 clinicians ranked their attitude toward computer-guided implant surgery (CGIS) and conventional non-computer-guided surgery (non-CGIS) in terms of advantages, disadvantages and clinical indications. Statistical analysis was conducted by the Spearman correlation test, Kruskal–Wallis test, and Wilcoxon rank sum tests, at a significance level of P< 0.05.Results: The survey results indicated that the most significant advantages of CGIS from the participants’ perspective were low levels of stress during surgery (P = 0.003) and minimal requirement of surgical skills (P = 0.04). Notably, the advantages of accurate outcome and predictable flapless surgery were not considered significantly higher for CGIS than for non-CGIS (P = 0.2 and 0.7, respectively). The high treatment cost was the most significant disadvantage of CGIS when compared to non-CGIS (P = 0.002), and complete edentulism was the most recommended clinical condition for CGIS.Conclusion: Clinicians acknowledged the advantages of CGIS over non-CGIS, especially in complete edentulism. The significant advantages of CGIS were the clinician’s state of low stress and minimal skills required rather than the patient’s interest in treatment predictability. CGIS is an attractive approach for most participants, in spite of the low rate of actual use.Keywords: clinician-based outcome, dental implant, guided placement

Michel Kabamba Nzaji,1,2 Leon Kabamba Ngombe,1,3 Guillaume Ngoie Mwamba,4 Deca Blood Banza Ndala,5 Judith Mbidi Miema,2 Christophe Luhata Lungoyo,2 Bertin Lora Mwimba,2 Aimé Cikomola Mwana Bene,2 Elisabeth Mukamba Musenga2 1Department of Public Health, Faculty of Medicine, University of Kamina, Kamina, Democratic Republic of Congo; 2Ministry of Health, National Expanded Program for Immunization, Operational Research Unit, Kinshasa, Democratic Republic of Congo; 3Department of Epidemiology and Public Health, Nursing Care Section, Higher Institute of Medical Techniques of Lubumbashi, Lubumbashi, Democratic Republic of Congo; 4VillageReach, Kinshasa, Democratic Republic of Congo; 5Department of Epidemiology and Public Health, Community Health Section, Higher Institute of Medical Techniques of Mbuji-Mayi, Mbuji-Mayi, Democratic Republic of CongoCorrespondence: Michel Kabamba Nzaji Tel +243978467432Email michelnzaji@yahoo.frPurpose: This study aims to estimate the acceptability of a future vaccine against COVID-19 and associated factors if offered in Congolese health-care workers (HCWs), since they have the highest direct exposure to the disease.Patients and Methods: We conducted an analytical cross-sectional study among 23 Congolese referral hospitals, including three university hospitals, located in three towns from March through 30 April 2020. The main outcome variable was healthcare workers’ acceptance of a future vaccine against COVID-19. The associated factors of vaccination willingness were identified through a logistic regression analysis.Results: A sample of 613 HCWs participated in the study and completed the study questionnaire, including 312 (50.9%) men and 301 (49.1%) women. Only 27.7% of HCWs said that they would accept a COVID-19 vaccine if it was available. From the logistic regression analysis, male healthcare workers (ORa=1.17, 95% CI: 1.15– 2.60), primarily doctors (ORa=1.59; 95% CI:1.03– 2.44) and having a positive attitude towards a COVID-19 vaccine (ORa=11.49; 95% CI: 5.88– 22.46) were significantly associated with reporting willingness to be vaccinated.Conclusion: For acceptability of vaccination against COVID-19 among others education among HCWs is crucial because health professionals’ attitudes about vaccines are an important determinant of their own vaccine uptake and their likelihood of recommending the vaccine to their patients.Keywords: COVID-19 vaccine, health-care workers, HCWs, acceptability, DRC

Alike W van der Velden,1 Aurelio Sessa,2 Attila Altiner,3 Antonio Carlos Campos Pignatari,4 Adrian Shephard5 1Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands; 2Italian College of General Practitioners and Primary Care, Florence, Italy; 3Institute of General Practice, Rostock University Medical Center, Rostock, Germany; 4Paulista School of Medicine (EPM), Federal University of São Paulo (UNIFESP), São Paulo, Brazil; 5Reckitt Benckiser Healthcare Ltd, Slough, UKCorrespondence: Alike W van der VeldenJulius Center for Health Sciences and Primary Care, University Medical Center Utrecht, STR 6.103, P.O. Box 85500, Utrecht, GA 3508, The NetherlandsEmail A.W.vanderVelden@umcutrecht.nlBackground: Acute sore throat is one of the most common problems for which patients consult their general practitioner and is a key area for inappropriate antibiotic prescribing. The objective of this study was to investigate patients’ attitudes related to healthcare-seeking behavior and self-management of sore throat.Methods: We conducted an observational, questionnaire-based study across 13 countries (Australia, Brazil, China, France, Germany, Italy, the Philippines, Russia, Saudi Arabia, South Africa, Thailand, the UK and the USA) on respondents who reported having had a sore throat in the previous 12 months. Data were collected on their experiences, contact with healthcare professionals, treatment practices and opinions about antibiotics.Results: A total of 5196 respondents (approximately 400 per country) completed the survey. Over 80% of respondents sought advice for a sore throat, with 30% consulting a general practitioner. The desire to limit the worsening of symptoms was the main reason for seeking treatment. Other reasons concerned resolving persistent symptoms and reducing the impact on daily life/sleep. Self-management for sore throat was mainly medicated sore throat remedies. “Wanting an antibiotic” was rated much lower (55%) than most other reasons for visiting a doctor, but this differed greatly between countries. The percentage of respondents using antibiotics varied widely, for example, 10% in the UK and 45% in Saudi Arabia. There was considerable variation in the proportion of respondents who thought that antibiotics would be effective against sore throat (from 24% in France to 94% in Saudi Arabia).Conclusions: Our findings suggest that knowledge of effective treatments for sore throat varied widely. The results of this study should enable healthcare professionals to better anticipate patients’ needs. This will support healthcare professionals in their role as antibiotic stewards, helping to reduce the misuse of antibiotics, and further guiding patients towards symptomatic self-management of sore throat.Keywords: primary care, community health, disease management, health literacy, medications, pharmacy

Robert G Hooper Center for Sleep Medicine, Mayo Clinic, Phoenix, Arizona, USACorrespondence: Robert G Hooper P.O. Box 4100, Scottsdale, Arizona 85261-4100, USATel +1-480-342-1019Fax +1-480-342-1012Email RHoop@thesleepcenteraz.comIntroduction: There are many options available to patients who are placed on constant positive airway pressure (CPAP) for obstructive sleep apnea. Despite the success of CPAP in correcting apnea, a significant number of patients have difficulty with the therapy. A large number of those patients who have difficulty stop therapy and are often labeled as “CPAP Failure”. Non-sleep specialists may view CPAP therapy as a singular course of treatment, but there are many ways CPAP may be ordered for a patient. Each patient experiences a unique set of options that constitute a unique order set.Methods: In order to demonstrate the magnitude of the possible options, estimates of the number of unique order sets were calculated. The author chose individual order options and the number of selections possible within each option. The calculated sets included a “Generous, Limited and Minimal” number of selections for each option. Calculations were done separately for standard CPAP and for auto-adjusting CPAP. Additional calculations were performed using the number of commercially available masks in the United States.Results: The maximum number of unique order sets was seen using a standard CPAP combined with commercially available masks: 49,152 unique order sets. The fewest number of unique order sets were seen with the auto-adjusting CPAP and the “Minimal” selections: 288 unique order sets.Discussion: There are a large number of unique CPAP orders that a patient may experience. CPAP treatment is not a singular or simple therapy. When evaluating obstructive sleep apnea patients with histories of CPAP failure or prior difficulty with CPAP, paying close attention to the patient’s treatment experiences may help explain a significant number of those patients’ CPAP therapy problems.Keywords: obstructive apnea, apnea treatment failure, CPAP, CPAP failure, CPAP orders, CPAP compliance

Hiroyoshi Yamazaki,1 Naoto Tsujimoto,1 Momoha Koyanagi,1 Megumi C Katoh,1 Koyuki Tajima,2 Mika Komori1 1Medicines Development Unit Japan and Medical Affairs, Eli Lilly Japan K.K., Kobe, Japan; 2Post Marketing Surveillance Clinical Research Department, Nippon Shinyaku Co., Ltd., Kyoto, JapanCorrespondence: Hiroyoshi YamazakiMedicines Development Unit Japan and Medical Affairs, Eli Lilly Japan K.K., Lilly Plaza One Bldg., 5-1-28, Isogamidori, Chuo-ku, Kobe 651-0086, JapanTel +81 78 242 4391Fax +81 78 242 9299Email yamazaki_hiroyoshi@lilly.comObjective: To evaluate the long-term safety and effectiveness of tadalafil in Japanese men with lower urinary tract symptoms secondary to benign prostatic hyperplasia in real-world clinical practice; and to investigate the safety profile in patients aged ≥ 75 years.PatientsandMethods: This was a prospective, non-interventional, multicenter, post-marketing surveillance study in which Japanese patients with lower urinary tract symptoms secondary to benign prostatic hyperplasia were observed for up to 18 months after initiating tadalafil treatment. The real-world safety and effectiveness outcomes were assessed at baseline and at 1, 3, 6, 12, and 18 months post-treatment or the last day of treatment.Results: Most patients received tadalafil 5 mg per day throughout the observation period. Among 1393 patients analyzed for safety, the overall incidence of adverse drug reactions was 8.3%. These adverse drug reactions were generally consistent with the known safety profile of tadalafil and no new safety risks were identified in long-term use. There was no statistical difference in the frequency of adverse drug reactions between patients aged < 75 and ≥ 75 years. The mean change in total International Prostate Symptom Score (IPSS) and IPSS-quality of life subscore was significantly improved at each timepoint. At 18 months, IPSS had improved by 5.0 points (P < 0.001) and IPSS-quality of life subscore had improved by 1.5 points (P < 0.001). The mean change in post-voiding residual urine volume from baseline was significant at each time point and was − 9.8 mL at 18 months (P < 0.001); there were no significant differences from baseline in maximum urinary flow rate.Conclusion: This surveillance demonstrated that tadalafil has favorable safety and effectiveness profiles for long-term use in Japanese men with lower urinary tract symptoms secondary to benign prostatic hyperplasia. In addition, safety profiles in patients aged ≥ 75 years were similar to patients aged < 75 years.Keywords: elderly patient, long-term, observational study, phosphodiesterase type 5 inhibitor

Kael Wherry,1 Kurt Stromberg,1 Jennifer A Hinnenthal,1 Lisa A Wallenfelsz,1 Mikhael F El-Chami,2 Lindsay Bockstedt1,3 1Medtronic, Plc, Mounds View, MN, USA; 2Division of Cardiology, Section of Electrophysiology, Emory University, Atlanta, GA, USA; 3Medtronic, Plc, Minneapolis, MN, USACorrespondence: Kael WherryMedtronic, Plc, 8200 Coral Sea Street NE, Mounds View, MN 55112, USATel +1 763.526.2288Email kael.wherry@medtronic.comBackground: There is heightened interest in how real-world data (RWD) can be used to supplement or replace traditional mechanisms for collecting clinical information. A critical component in evaluating utility of RWD is assessing the validity and reliability of event measurement. Only two studies have validated Medicare claims with physician-adjudicated data collected in a clinical study and none in the pacemaker patient population. This study compares events identified in physician-adjudicated clinical registry data collected in the Micra Post-Approval Registry (PAR) with events identified via Medicare administrative claims in the Micra Coverage with Evidence (CED) Study.Methods: Patients who were dually enrolled in the Micra CED and the Micra PAR between March 9, 2017 and December 1, 2017 were included in the validation analysis. All patients intended to be implanted with a Micra device were eligible for participation in the Micra PAR. All Medicare fee-for-service beneficiaries implanted with a Micra device who met the 12-month continuous enrollment criteria were included in the Micra CED. We compared the count of acute (30-day) complications identified in the Medicare claims and the physician-adjudicated PAR data to assess agreement between data sources.Results: There were 230 patients dually enrolled in the Micra CED and Micra PAR studies during the study period. Overall, there were 17 acute events reported in either the Micra CED or the Micra PAR, with 95% agreement in the identification of events and absence of events between studies. Study disagreement between events reported in either study varied: arteriovenous fistula (50%), pulmonary embolism (67%), hemorrhage/hematoma (75%), and deep vein thrombosis (100%). Among physician-adjudicated events, there was no disagreement between the Micra CED and Micra PAR studies in any event type.Conclusion: Findings from this study demonstrate high agreement in event identification between Medicare claims data and registries for patients implanted with Micra leadless pacemakers.Keywords: administrative claims, validation, Medicare, registry, leadless pacemaker

Christopher S Ambrose,1 Bradley E Chipps,2 Wendy C Moore,3 Weily Soong,4 Jennifer Trevor,5 Dennis K Ledford,6 Warner W Carr,7 Njira Lugogo,8 Frank Trudo,9 Trung N Tran,10 Reynold A Panettieri Jr11 1US Medical Affairs, AstraZeneca, Gaithersburg, MD, USA; 2Capital Allergy & Respiratory Disease Center, Sacramento, CA, USA; 3Pulmonary, Critical Care, Allergy, and Immunologic Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA; 4Alabama Allergy & Asthma Center, Birmingham, AL, USA; 5Pulmonary, Allergy, & Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; 6Division of Allergy and Immunology, University of South Florida, Tampa, FL, USA; 7Allergy & Asthma Associates of Southern California, Mission Viejo, CA, USA; 8Pulmonary & Critical Care Medicine, University of Michigan, Ann Arbor, MI, USA; 9US Medical Affairs, AstraZeneca, Wilmington, DE, USA; 10Biopharmaceuticals Medical, Respiratory and Immunology, AstraZeneca, Gaithersburg, MD, USA; 11Institute for Translational Medicine and Science, Rutgers, The State University of New Jersey, New Brunswick, NJ, USACorrespondence: Christopher S Ambrose Tel +1 (301) 398-4454Fax +1 301-398-9454Email chris.ambrose@astrazeneca.comBackground: Approximately 5– 10% of patients with asthma have severe disease. High-quality real-world studies are needed to identify areas for improved management.Objective: Aligned with the International Severe Asthma Registry, the CHRONICLE study (ClinicalTrials.gov: NCT03373045) was developed to address this need in the US.Study Design: Learnings from prior studies were applied to develop a real-world, prospective, noninterventional study of US patients with confirmed severe asthma who are treated by subspecialist physicians and require biologic or maintenance systemic immunosuppressant therapy or who are uncontrolled by high-dosage inhaled corticosteroids and additional controllers. Target enrollment is 4000 patients, with patient observation for ≥ 3 years. A geographically diverse sample of allergist/immunologist and pulmonologist sites approach all eligible patients under their care and report patient characteristics, treatment, and health outcomes every 6 months. Patients complete online surveys every 1– 6 months.Initial Results: From February 2018 to February 2019, 102 sites screened 1428 eligible patients; 936 patients enrolled. Study sites (40% allergist/immunologist, 42% pulmonologist, 18% both) were similar to other US asthma subspecialist samples. Enrolled patients were 67% female with median ages at enrollment and diagnosis of 55 (range: 18– 89) and 26 (0– 80) years, respectively. Median body mass index was 31 kg/m2; 3% and 29% were current or former smokers, respectively, and > 60% reported ≥ 1 exacerbation in the prior year and suboptimal symptom control.Conclusion: CHRONICLE will provide high-quality provider- and patient-reported data from a large, real-world cohort of US adults with subspecialist-treated severe asthma.Keywords: asthma exacerbations, longitudinal studies, allergists, pulmonologists, biologic therapy

Pattarawadee Sattanakho,1 Pilaiwan Kleebkaow,1 Ussanee Sangkomkumhang,2 Sukjai Booranabunyat,3 Pranom Buppasiri1 1Department of Obstetrics and Gynaecology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; 2Department of Obstetrics and Gynecology, Khon Kaen Regional Hospital, Khon Kaen, Khon Kaen Province, Thailand; 3Department of Obstetrics and Gynecology, Mahasarakham Hospital, Mahasarakham Province, ThailandCorrespondence: Pranom BuppasiriDepartment of Obstetrics and Gynaecology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, ThailandTel +66-43-202489Fax +66-43-348395Email bprano@kku.ac.thBackground and Objectives: To determine the rate of significant endometrial abnormalities in premenopausal women at low risk for endometrial hyperplasia and cancer presenting with abnormal uterine bleeding (AUB).Patients and Methods: This descriptive study was conducted from January 1, 2016 to March 31, 2019. The inclusion criteria were premenopausal women, 35– 50 years, presenting with AUB, low risk for endometrial hyperplasia or endometrial cancer, and having undergone endometrial sampling or uterine curettage. Nulliparous, obesity, diabetes mellitus, polycystic ovary syndrome, chronic anovulation, infertility, tamoxifen therapy and/or a family history of uterine, ovarian, breast and colon cancer were excluded. Data regarding baseline characteristics were collected, and histopathology reports were reviewed.Results: During the study period, 644 subjects were recruited, 557 of whom had adequate endometrial tissue for histopathology study. The pathology demonstrated benign in most cases (96%). The rate of significant abnormal endometrial pathology was 4% (23 cases) including 19 cases of endometrial hyperplasia without atypia (3.3%), and 4 cases of endometrial cancer (0.7%).Conclusion: The rate of significant abnormal endometrial pathology in premenopausal women at low risk for endometrial hyperplasia or endometrial cancer presenting with AUB was very low. This information should be incorporated into the counseling process regarding the risks and benefits of endometrial sampling.Keywords: abnormal uterine bleeding, endometrial sampling, endometrial pathology

Jennifer Blythe,1 Eva Herrmann,2 Dominik Faust,3 Stephan Falk,4 Tina Edwards-Lehr,5 Florian Stockhausen,6 Ernst Hanisch,5 Alexander Buia5 1Department of Internal Medicine, Bürgerhospital Frankfurt, Frankfurt, Germany; 2Institute for Biostatistics and Mathematical Modelling, University Hospital Goethe University, Frankfurt, Germany; 3Department of Gastroenterology, Hepatology and Infectious Disease, Asklepios Klinik Langen, Langen, Germany; 4OptiPath Pathology Associates Frankfurt, Frankfurt, Germany; 5Department of Visceral and Thoracic Surgery, Asklepios Klinik Langen, Langen, Germany; 6Department of Surgery, Hospital zum Heiligen Geist, Frankfurt, Germany Background: For decades, the optimal timing of surgery for acute cholecystitis has been controversial. Recent meta-analyses and population-based studies favor early surgery. One recent large randomized trial has demonstrated that a delayed approach increases morbidity and cost compared to early surgery within 24hours of hospital admission. Since cases of severe cholecystitis were excluded from this trial, we argue that these results do not reflect real-world clinical situations. From our point of view, these results were in contrast to the clinical experience with our patients; so, we decided to analyze critically all our patients with the null hypothesis that the patients treated with a delayed cholecystectomy after an acute cholecystitis have a similar or even better outcome than those treated with an early operative approach.Patients and methods: We retrospectively analyzed clinical data from all patients with cholecystectomies in the period between January 2006 and September 2015. A total of 1,723 patients were categorized into four groups: early (n=138): urgent surgery of patients with acute cholecystitis within the first 72 hours of the onset of symptoms; intermediate (n=297): surgery of patients with acute cholecystitis within an average of 10 days after the onset of symptoms; delayed (n=427): initial non-surgical treatment of acute cholecystitis with surgery performed within 6–12 weeks of the onset of symptoms; and elective (n=868): cholecystectomy within a symptom-free interval of choice in patients with symptomatic cholecystolithiasis without signs of acute cholecystitis.Results: In a real-world scenario, early/intermediate cholecystectomy in acute cholecystitis was associated with a significant increase in morbidity and mortality (Clavien–Dindo score) compared to a delayed approach with surgery performed 6–12 weeks after the onset of symptoms. The adjusted linear rank statistics showed a decrease in the complication score with values of 2.29 in the early group, 0.48 in the intermediate group, –0.26 in the delayed group and –2.12 in the elective group. The results translate into a continuous decrease of the complication score from early over intermediate and delayed to the elective group.Conclusion: These results demonstrate that delayed cholecystectomy can be performed safely. In cases with severe cholecystitis, early and/or intermediate approaches still have a relatively high risk of morbidity and mortality. Keywords: acute cholecystitis, early cholecystectomy, delayed cholecystectomy, gallstone disease

Stavros Theologou,1 Konstantinos Giakoumidakis,1 Christos Charitos2 1Cardiac Surgery Intensive Care Unit, “Evangelismos” General Hospital of Athens, Athens, Greece; 2Department of Cardiothoracic Surgery, “Evangelismos” General Hospital of Athens, Athens, Greece Background: Delirium is a quite common complication in adult patients post-cardiac surgery. The purpose of our study was to identify perioperative characteristics and also focus on incidence factors that could predict delirium in the cardiac surgery intensive care unit (CICU) postoperatively. Methods: We conducted a prospective study of 179 consecutive patients, who underwent open-heart surgical operation and were admitted to the CICU of a general tertiary hospital in Athens, Greece. The patients were screened for delirium by using the diagnostic tools of Richmond Agitation Sedation Scale (RASS score) and the Confusion Assessment Method – ICU (CAM-ICU). The delirium assessment was carried out on the 1st and the 2nd postoperative day, and was conducted twice every nursing shift. A short questionnaire on sociodemographics and clinical patient characteristics was used for data collection purposes. Results: A total of 179 patients who underwent open-heart surgical operation with cardiopulmonary bypass (CPB) were enrolled in our study. The 2-day incidence of postoperative delirium in ICU was 11.2% (n=20/179). The main independent predictors of delirium on the 2nd postoperative day were neutrophil-to-lymphocyte ratio (p=0.001) and urea levels (p=0.016). Additionally, increased perioperative creatinine (p=0.006) and sodium (p=0.039) levels were significantly associated with delirium occurrence. Furthermore, elevated EuroSCORE (p=0.001), extended length of stay (LOS) in ICU (p

Sabrina Mueller,1 Antje Groth,1 Stefan G Spitzer,2,3 Anja Schramm,4 Andreas Pfaff,5 Ulf Maywald6 1Institute for Pharmacoeconomics and Medication Logistics, University of Wismar, Wismar, Germany; 2Praxisklinik Herz und Gefäße Dresden, Academic Educational Practice Clinic, TU Dresden, Dresden, Germany; 3Institute of Medical Technology, Brandenburg University of Technology Cottbus–Senftenberg, Senftenberg, Germany; 4AOK Bayern, Regensburg, Germany; 5AOK Baden-Württemberg, Stuttgart, Germany; 6AOK PLUS, Dresden, Germany Objective: To compare the real-world effectiveness and safety of non-vitamin-K-antagonist oral anticoagulant (NOAC) treatment in atrial fibrillation (AF) patients with a vitamin-K-antagonist (VKA)-based treatment. Methods: This was a retrospective analysis of an anonymized claims dataset from 3 German health insurance funds covering the period from January 01, 2010 to June 30, 2014, with a minimum observation time of 12 months. All continuously insured patients with at least 2 outpatient AF diagnoses and/or 1 inpatient respective diagnosis who received at least 1 outpatient prescription of a NOAC or VKA were included. Outcomes and measures: Death, ischemic strokes (IS), non-specified strokes, transient ischemic attacks (TIAs), myocardial infarctions (MIs), arterial embolism (AE), hemorrhagic strokes, severe bleedings, and composite outcomes. Main comparisons were done based on propensity score-matched (PSM) cohorts. Results were reported as incidence rate ratios and hazard ratios (HRs). Results: We assigned 37,439 AF patients to each PSM cohort (NOAC cohort: mean age 78.2 years, mean CHA2DS2VASc score 2.96, mean follow-up 348.5 days; VKA cohort: mean age 78.2 years, mean CHA2DS2VASc 2.95, mean follow-up 365.5 days). NOAC exposure was associated with significantly higher incidence rate ratios; 95% CI/HRs; 95% CI for the following outcomes: death (1.22; 1.17–1.28/1.22; 1.17–1.28), IS (1.90; 1.69–2.15/1.92; 1.69–2.19), non-specified strokes (2.04; 1.16–3.70/1.93; 1.13–3.32), TIAs (1.52; 1.29–1.79/1.44; 1.21–1.70), MIs (1.26; 1.10–1.15/1.31; 1.13–1.52), AE (1.75; 1.32–2.32/1.81; 1.36–2.34) and severe bleeding (1.92; 1.71–2.15/1.95; 1.74–2.20). Multivariable Cox regression analyses and additional sensitivity analysis, including analysis of PSM-matched NOAC/VKA treatment-naive patients, only confirmed the above results. The study was documented under clinicaltrials.gov (NCT02657616). Conclusion and relevance: A VKA therapy seems to be more effective and safer than a NOAC therapy in a real-world cohort of German AF patients. Keywords: atrial fibrillation, AF, anticoagulation, NOAC, VKA, cohort study

Kahasse Gebrekidan,1 Alemayehu Worku21Department of Public Health, Saint Paul Hospital Millennium Medical College, Addis Ababa, Ethiopia; 2Department of Preventive Medicine, School of Public Health, College of Health Science, Addis Ababa University, Addis Ababa, Ethiopia Background: Although Ethiopia has shown remarkable achievements in reducing maternal mortality in the last 10 years, the prevalence of late antenatal care (ANC) initiation is still high in the country.Objective: The primary purpose of this study was to identify the factors related to late ANC initiation among pregnant women in selected public health centers in Addis Ababa, Ethiopia.Subjects and methods: A total of 402 pregnant women (cases=134, controls=268) were recruited using multistage sampling. The design selected for the study was unmatched case–­control. EpiData version 3.02 and SPSS version 20.0 were used for data entry and statistical analysis, respectively. Binary logistic regression model was used to model the odds of late ANC initiation.Results:The odds of attending ANC late were significantly higher for mothers with a monthly household income of $8.50 to start the ANC service (AOR=3.04; 95% CI: 1.98, 4.67).Conclusion: Low educational level, low income of the household, unplanned pregnancy, stay for

Objectives To describe the epidemiology of abortion in Ecuador from 2004 to 2014 and compare the prevalence between the public and the private health care systems. Methods This is a cross-sectional analysis of the overall mortality and morbidity rate due to abortion in Ecuador, based on public health records and other government databases. Results From 2004 to 2014, a total of 431,614 spontaneous abortions, miscarriage and other types of abortions were registered in Ecuador. The average annual rate of abortion was 115 per 1,000 live births. The maternal mortality rate was found to be 43 per 100,000 live births. Conclusions Abortion is a significant and wide-ranging problem in Ecuador. The study supports the perception that in spite of legal restrictions to abortion in Ecuador, women are still terminating pregnancies when they feel they need to do so. The public health system reported >84% of the national overall prevalence., Video abstract

Franco Maggiolo,1 Elisa Di Filippo,1 Laura Comi,1 Annapaola Callegaro,2 Giorgio L Colombo,3,4 Sergio Di Matteo,4 Daniela Valsecchi,5 Marco Rizzi1 1USC of Infectious Diseases, 2USC Microbiology and Virology, 3Department of Drug Sciences, University of Pavia, 4S.A.V.E. Studi– Health Economics & Outcomes Research, Milan, 5USC of Pharmacy, ASST Papa Giovanni XXIII, Bergamo,Italy Abstract: The source and significance of residual low-level viremia (LLV) during combinational antiretroviral therapy (cART) remain a matter of controversy. It is unclear whether residual viremia depends on ongoing release of HIV from the latent reservoir or if viral replication contributes to LLV. We examined the relationship between adherence and LLV. Adherence was estimated by pharmacy refill and dichotomized as ≥95% or 3: constantly between 3 and 50 ­copies/mL; and V>50: a measure of >50 copies/mL minimum. Overall, 2789 patients were included. At each time point approximately 92% of the patients presented an HIV-RNA 50copies/mL minimum. The mean adherence rate was 92.1% (95% confidence interval [CI] from 91.1% to 93.1%) in K3 patients and to 88.4% in V>50 patients (P3 and to 48% in V>50. Moreover, 34% of patients with a steady adherence 3, whereas 21.7% of those with a drug holiday (21.7%) were observed in the V>50 group (P=0.002). A steady viral suppression can occur despite moderate cART non-adherence, but reduced adherence is associated with low-level residual viremia, which could reflect new rounds of HIV replication. However, a detectable HIV-RNA could also be detected in patients with optimal cART adherence, indicating additional mechanisms favoring HIV persistence. Keywords: adherence, drug-refill, LLV, low-level viremia, viral replication, residual viremia cART

Julian WE Jarman,1 Tina D Hunter,2 Wajid Hussain,1 Jamie L March,3 Tom Wong,1 Vias Markides1 1Cardiology & Electrophysiology, Heart Rhythm Center, NIHR Cardiovascular Research Unit, The Royal Brompton Hospital, and National Heart and Lung Institute, Imperial College London, London, UK; 2Health Outcomes Research, CTI Clinical Trial & Consulting Services Inc., Cincinnati, OH, 3Health Economics and Market Access, Biosense Webster Inc., Diamond Bar, CA, USA Background: We sought to determine whether catheter ablation of atrial fibrillation (AF) is associated with reduced occurrence of ischemic cerebrovascular events.Methods and results: Using routinely collected hospital data, ablation patients were matched to two control cohorts via direct and propensity score matching. A total of 4,991 ablation patients were matched 1:1 to general AF controls with no ablation, and 5,407 ablation patients were similarly matched to controls who underwent cardioversion. Yearly rates of ischemic stroke or transient ischemic attack (stroke/TIA) before and after an index date were compared between cohorts. Index date was defined as the first ablation, the first cardioversion, or the second AF event in the general AF cohort. Matched populations had very similar demographic and comorbidity profiles, including nearly identical CHA2DS2-VASc risk distribution (p-values 0.6948 and 0.8152 vs general AF and cardioversion cohorts). Statistical models of stroke/TIA risk in the preindex period showed no difference in annual event rates between cohorts (mean±standard error 0.30% ± 0.08% ablation vs 0.28% ± 0.07% general AF, p=0.8292; 0.37% ± 0.09% ablation vs 0.42% ± 0.08% cardioversion, p=0.5198). Postindex models showed significantly lower annual rates of stroke/TIA in ablation patients compared with each control group over 5 years (0.64% ± 0.11% ablation vs 1.84% ± 0.23% general AF, p

Benton R Hunter,1 Sean P Collins,2 Gregory J Fermann,3 Phillip D Levy,4 Changyu Shen,5 Syed Imran Ayaz,4 Mette L Cole,1 Karen F Miller,2 Adam A Soliman,3 Peter S Pang1,6 1Department of Emergency Medicine, Indiana University School of Medicine, Indianapolis, IN, 2Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, TN, 3Department of Emergency Medicine, University of Cincinnati, Cincinnati, OH, 4Department of Emergency Medicine, Wayne State University School of Medicine, Detroit, MI, 5Department of Biostatistics, Indiana University School of Medicine, 6Department of Indianapolis EMS, The Regenstrief Institute, IN, USA Background: Acute heart failure (AHF) is a common presentation in the Emergency Department (ED), and most patients are admitted to the hospital. Identification of patients with AHF who have a low risk of adverse events and are suitable for discharge from the ED is difficult, and an objective tool would be useful. Methods: The highly sensitive Troponin T Rules Out Acute Cardiac Insufficiency Trial (TACIT) will enroll ED patients being treated for AHF. Patients will undergo standard ED evaluation and treatment. High-sensitivity troponin T (hsTnT) will be drawn at the time of enrollment and 3 hours after the initial draw. The initial hsTnT draw will be no more than 3 hours after initiation of therapy for AHF (vasodilator, loop diuretic, noninvasive ventilation). Treating clinicians will be blinded to hsTnT results. We will assess whether hsTnT, as a single measurement or in series, can accurately predict patients at low risk of short-term adverse events. Conclusion: TACIT will explore the value of hsTnT measurements in isolation, or in combination with other markers of disease severity, for the identification of ED patients with AHF who are at low risk of short-term adverse events. Keywords: heart failure, high-sensitivity troponin, hospitalization

David B Price,1,2 Eran Gefen,3 Gokul Gopalan,4 Cristiana Miglio,2 Rosie McDonald,2 Vicky Thomas,2 Simon Wan Yau Ming2 1Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK; 2Observational and Pragmatic Research Institute, Singapore, Singapore; 3Teva Pharmaceuticals, Petach Tikva, Israel; 4Teva Pharmaceuticals, Frazer, PA, USA Objective: The objective of this study was to determine whether the effectiveness of budesonide comparator is non-inferior to budesonide reference in the prevention of asthma exacerbations. Asthma-related hospitalizations and safety were also examined.Methods: This study used a matched, historic cohort design. Data were drawn from the Clinformatics™ Data Mart US claims database and included a 1-year baseline, starting 1year before the index prescription date, and a 1-year outcome period. Patients received budesonide comparator or reference treatment. The primary outcome was the rate of asthma exacerbations. Non-inferiority for budesonide comparator vs budesonide reference was established if the 95% confidence interval (CI) upper limit of mean difference in proportions between treatments was

Konstantinos Giakoumidakis,1 Nikolaos V Fotos,2 Athina Patelarou,3 Stavros Theologou,1 Mihalis Argiriou,4 Anastasia A Chatziefstratiou,2 Christina Katzilieri,5 Hero Brokalaki2 1Cardiac Surgery Intensive Care Unit, “Evangelismos” General Hospital of Athens, 2Faculty of Nursing, School of Healthcare Sciences, National & Kapodistrian University of Athens, Athens, 3Department of Anaesthesiology, University Hospital of Heraklion, Heraklion, 4Department of Cardiothoracic Surgery, “Evangelismos” General Hospital of Athens, 5Intensive Care Unit, “Korgalenio – Benakio Hellenic Red Cross” General Hospital of Athens, Athens, Greece Purpose: The purpose of the present study was to investigate the association between the perioperative neutrophil to lymphocyte ratio (NLR) and cardiac surgery patient outcomes.Patients and methods: A retrospective cohort study of 145 patients who underwent cardiac surgery in a tertiary hospital of Athens, Greece, from January to March 2015, was conducted. By using a structured short questionnaire, this study reviewed the electronic hospital database and the medical and nursing patient records for data collection purposes. The statistical significance was two-tailed, and p-values

Anne Burden,1 Nicolas Roche,2 Cristiana Miglio,1 Elizabeth V Hillyer,1 Dirkje S Postma,3 Ron MC Herings,4 Jetty A Overbeek,4 Javaria Mona Khalid,5 Daniela van Eickels,6 David B Price1,7 1Observational and Pragmatic Research Institute Pte Ltd, Singapore; 2University Paris Descartes (EA2511), Cochin Hospital Group (AP-HP), Paris, France; 3Department of Pulmonology, University Medical Center Groningen, University of Groningen, Groningen, 4PHARMO Institute for Drug Outcomes Research, Utrech, the Netherlands; 5Takeda Development Centre Europe Ltd, London, UK; 6Takeda Pharmaceuticals International GmbH, Zurich, Switzerland; 7Academic Primary Care, University of Aberdeen, Aberdeen, UK Background: Cohort matching and regression modeling are used in observational studies to control for confounding factors when estimating treatment effects. Our objective was to evaluate exact matching and propensity score methods by applying them in a 1-year pre–post historical database study to investigate asthma-related outcomes by treatment. Methods: We drew on longitudinal medical record data in the PHARMO database for asthma patients prescribed the treatments to be compared (ciclesonide and fine-particle inhaled corticosteroid [ICS]). Propensity score methods that we evaluated were propensity score matching (PSM) using two different algorithms, the inverse probability of treatment weighting (IPTW), covariate adjustment using the propensity score, and propensity score stratification. We defined balance, using standardized differences, as differences of 10% for four variables in the exact-matched dataset and

Naomi Launders,1 Dermot Ryan,2 Christopher C Winchester,3 Derek Skinner,4 Priyanka Raju Konduru,4 David B Price4 1Respiratory Effectiveness Group, Cambridge, UK; 2Allergy and Respiratory Research Group, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Medical School, Edinburgh EH8 9AG, Scotland; 3Oxford PharmaGenesis, Oxford, UK; 4Observational and Pragmatic Research Institute Pte Ltd, Singapore, SingaporeCorrespondence: David B PriceObservational and Pragmatic Research Institute Pte Ltd (OPRI), 60 Paya Lebar Road, Paya Lebar Square, Level 5, Unit 33 and 34, Singapore 409051, SingaporeTel +65 68029724Email dprice@opri.sgPurpose: In primary care, initial diagnosis of community-acquired pneumonia (CAP) is made on clinical judgment without radiological confirmation or knowledge of the causative organism. Use of CRB65 score has been recommended for assessing the severity of CAP and thereby determining clinical management, but it is not known how frequently these scores are used in primary care.Patients and methods: Primary care consultations in adults with a diagnostic code for CAP between 1 January 2009 and 31 December 2016 were extracted from the Optimum Patient Care Research Database, which at the time of data extraction had over 3.4 million patients in the UK. Episodes without antibiotic prescription on day of diagnosis were excluded, as were records describing past events. Patients admitted to hospital on day of diagnosis were excluded, but were included in exploratory analysis of CRB65 recording.Results: In total, 4734 episodes of CAP in adults managed in primary care between 1 January 2009 and 31 December 2016 were included. A range of investigations/observations were recorded, including pulse rate (10.7%), chest examinations (9.1%) and blood tests (5.4%). CRB65 scores were recorded in 19 (0.4%) episodes of CAP, 17 of which were after the publication of the NICE guidelines in December 2014. CRB65 recording was no more frequent in 3819 episodes referred to hospital (12, 0.3%; p=0.63), but where recorded, CRB65 scores were higher (Median: 1.0 [interquartile range: 0.5–1.0] vs 2.0 [interquartile range: 1.0–2.0], p=0.04). The most commonly prescribed antibiotic was amoxicillin (40.3%), and 85.9% of episodes had a prescription length of seven days.Conclusion: CRB65 scores are seldom recorded in UK primary care. Given that these scores are embedded in UK guidelines, further work is required to assess feasibility and barriers to use of CRB65 scores in primary care.Keywords: lower-respiratory tract infection, antibiotics, antimicrobials, guidelines adherence, CRB65

Vibeke Backer,1 Leif Bjermer,2 Olav Kåre Refvem,3 Andreas Søderman,4 Spencer Jones51Department of Respiratory Medicine, Bispebjerg Hospital, Copenhagen University, 48 2400 Copenhagen, Denmark; 2Department of Respiratory Medicine and Allergology, Skåne University Hospital, 221 85 Lund, Sweden; 3Lungepraksis AS, Oslo 0873, Norway; 4Medical Affairs Nordics, Sandoz AS, Copenhagen, DK-2300, Denmark; 5Global Medical Affairs, Sandoz International GmbH, Holzkirchen, D-83607, GermanyBackground: The design of inhaler devices may potentially influence adherence/persistence and outcomes in asthma.Objective: The primary objective was to assess asthma control and any change in the quality of life in patients using an intuitive dry powder inhaler containing fluticasone propionate/salmeterol (AirFluSal®, Forspiro®,) for the treatment of asthma in everyday practice.Methods: ASSURE was a multicenter, noninterventional, open-label, prospective study in patients with asthma, aged ≥12 years and treated with the Forspiro device in Denmark, Sweden and Norway. Patients’ opinions of their asthma control were assessed by the Asthma Control Test (ACT) questionnaire and asthma-related quality of life by the Mini Asthma Quality of Life Questionnaire (miniAQLQ) at baseline and at two follow-up visits (approximately 4–8-week intervals).Results: Of 321 patients enrolled in the study, 299 received at least one dose of fluticasone propionate/salmeterol via the Forspiro device and 204 had evaluable data at the baseline visit and at least one later visit. Patients showed improvements in asthma control and quality of life during the study. The mean sum score of ACT increased from 18.0 (SD 4.5) at visit 1 to 19.9 (4.2) at visit 2 and 20.5 (4.3) at visit 3. Overall, 38.2% of patients improved by the minimal clinically important difference (MCID) of ≥3 points (45.6% among those with a baseline score below 23 [ie, not already well controlled]). The mean score on the miniAQLQ increased from 5.16 (SD 1.24) at visit 1 to 5.58 (SD 1.20) at visit 2 and 5.82 (SD 1.04) at visit 3. Overall, 42.6% of patients improved by the MCID of ≥0.5.Conclusion: This real-life study suggests that treatment with fluticasone propionate/salmeterol via the Forspiro device can improve asthma symptom control and quality of life.Keywords: asthma, fluticasone propionate, salmeterol, symptom control, quality of life

Joe Alexander Jr,1,* Roger A Edwards,2,* Luigi Manca,3 Roberto Grugni,3 Gianluca Bonfanti,3 Birol Emir,4 Ed Whalen,4 Steve Watt,1 Marina Brodsky,5 Bruce Parsons6 1Global Medical Affairs, Pfizer Inc, New York, NY 10017, USA; 2Health Services Consulting Corporation, Boxborough, MA 01719, USA; 3Fair Dynamics Consulting, SRL, Milan, Italy; 4Global Statistics, Pfizer Inc, New York, NY 10017, USA; 5Global Medical Affairs, Pfizer Inc, Groton, CT 06340, USA; 6Global Medical Product Evaluation, Pfizer Inc, New York, NY 10017, USA*These authors contributed equally to this workCorrespondence: Roger A EdwardsHealth Services Consulting Corporation, 169 Summer Road, Boxborough, MA 01719, USATel +1 508472-0406 Fax +1 978264-0713Email redwards.hscc@gmail.comPurpose: Variability in patient treatment responses can be a barrier to effective care. Utilization of available patient databases may improve the prediction of treatment responses. We evaluated machine learning methods to predict novel, individual patient responses to pregabalin for painful diabetic peripheral neuropathy, utilizing an agent-based modeling and simulation platform that integrates real-world observational study (OS) data and randomized clinical trial (RCT) data.Patients and methods: The best supervised machine learning methods were selected (through literature review) and combined in a novel way for aligning patients with relevant subgroups that best enable prediction of pregabalin responses. Data were derived from a German OS of pregabalin (N=2642) and nine international RCTs (N=1320). Coarsened exact matching of OS and RCT patients was used and a hierarchical cluster analysis was implemented. We tested which machine learning methods would best align candidate patients with specific clusters that predict their pain scores over time. Cluster alignments would trigger assignments of cluster-specific time-series regressions with lagged variables as inputs in order to simulate “virtual” patients and generate 1000 trajectory variations for given novel patients.Results: Instance-based machine learning methods (k-nearest neighbor, supervised fuzzy c-means) were selected for quantitative analyses. Each method alone correctly classified 56.7% and 39.1% of patients, respectively. An “ensemble method” (combining both methods) correctly classified 98.4% and 95.9% of patients in the training and testing datasets, respectively.Conclusion: An ensemble combination of two instance-based machine learning techniques best accommodated different data types (dichotomous, categorical, continuous) and performed better than either technique alone in assigning novel patients to subgroups for predicting treatment outcomes using microsimulation. Assignment of novel patients to a cluster of similar patients has the potential to improve prediction of patient outcomes for chronic conditions in which initial treatment response can be incorporated using microsimulation.Clinical trial registries: www.clinicaltrials.gov: NCT00156078, NCT00159679, NCT00143156, NCT00553475.Keywords: coarsened exact matching, hierarchical cluster analysis, time series regressions, agent-based modeling and simulation, machine learning &nbsp

Saeed Akhlaghi,1 Maryam Sahebari,2 Mahmoud Mahmoodi,1 Mehdi Yaseri,1 Mohammad Ali Mansournia,1 Hojjat Zeraati11Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran; 2Rheumatic Diseases Research Center (RDRC), Mashhad University of Medical Sciences, Mashhad, IranBackground and objectives: Following the discovery of new drugs, physicians and pharmaceutical companies have become interested in examining patients’ mortality and morbidity rates. In this respect, the effects of methotrexate (MTX)+etanercept/infliximab (ETA/INF) therapy on the survival of rheumatoid arthritis patients (RA) were evaluated in this study using marginal structural piecewise constant baseline hazard model.Patients and methods: According to the standard protocol, MTX is considered as the first-line treatment for RA patients. If there is no adequate response to MTX, biologic drugs will be added. To compare the survival rates of RA patients in MTX- and MTX+ETA/INF-treated groups, the piecewise constant baseline hazard model was fitted. Then, due to the existence of the time-dependent confounder (VAS) which was affected by previous treatment, the weight for each person-time was calculated via the inverse probability treatment weighting method. These weights were then used by marginal structural piecewise constant baseline hazard model. Finally, these models were compared.Results: The median (IQR) of the follow-up period in patients receiving MTX+ETN/INF and MTX was 11 (15.25) and 11 (31), respectively, and the 8-year survival rate was reported by 70% versus 68%, respectively. First, the piece-wise constant baseline hazard model was fitted. Fitting the given model showed that MTX+ETA/INF had a significant effect on patients’ survival (HR=0.789, 95% CI [0.634, 0.983]). Second, marginal structural piecewise constant baseline hazard model was fitted. But, the results of this model revealed that MTX+ETA/INF did not have a significant impact on patients’ survival (HR=0.968, 95% CI [0.860, 1.090]).Conclusion: Adjusting the pain score over time as a time-dependent confounder via marginal structural piecewise constant baseline hazard model, it has been demonstrated that MTX+ETA/INF does not have a significant effect on patients’ survival rates. Therefore, a significant difference can be found between survival rates of these groups using longitudinal studies.Keywords: survival, biologics, IPTW, propensity score, time-dependent confounder, marginal structural models, piece-wise constant baseline hazard model

Ezra Fishman,1 John Barron,2 Ying Liu,1 Santosh Gautam,1 Justin E Bekelman,3 Amol S Navathe,4 Michael J Fisch,5 Ann Nguyen,6 Gosia Sylwestrzak1 1Translational Research, HealthCore, Inc., Wilmington, DE, USA; 2Clinical & Scientific Leadership, HealthCore, Inc., Wilmington, DE, USA; 3Radiation Oncology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA; 4Health Policy and Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA; 5Medical Oncology, AIM Specialty Health, Chicago, IL, USA; 6Oncology & Palliative Care Solutions, Anthem Inc., Woodland Hills, CA, USA Background: Alternative payment models frequently require attribution of patients to individual physicians to assign cost and quality outcomes. Our objective was to examine the performance of three methods for attributing a patient with cancer to the likeliest physician prescriber of anticancer drugs for that patient using administrative claims data.Methods: We used the HealthCore Integrated Research Environment to identify patients who had claims for anticancer medication along with diagnosis codes for breast, lung, or colorectal lung cancer between July 2013 and September 2017. The index date was the first date with a record for anticancer medication and cancer diagnosis code. Included patients had continuous medical coverage from 6 months before index to at least 7 days after index. Patients who received anticancer drugs during the 6 months prior to index were excluded. The three methods attributed each patient to the physician with whom the patient had the most evaluation and management (E&M) visits within a 90-day window around the index date (Method 1); the most E&M visits with no time window (Method 2); or the E&M visit nearest in time to the index date (Method 3). We assessed the performance of the methods using the percentage of the study cohort successfully attributed to a physician, and the positive predictive value (PPV) relative to available physician-reported data on patient(s) they treat.Results: In total, 70,641 patients were available for attribution to physicians. Percentages of the study cohort attributed to a physician were: Method 1, 92.6%; Method 2, 96.9%; and Method 3, 96.9%. PPVs for each method were 84.4%, 80.6%, and 75.8%, respectively.Conclusion: We found that a claims-based algorithm – specifically, a plurality method with a 90-day time window – correctly attributed nearly 85% of patients to a prescribing physician. Claims data can reliably identify prescribing physicians in oncology. Keywords: alternative payment model, specialty care, plurality rule, pay for performance

Brian Rayner Kidney and Hypertension Research Unit, University of Cape Town, Groote Schuur Hospital, Observatory, Cape Town 7925, South Africa Purpose: To describe the efficacy of a stratified approach on automatic office blood pressure (BP), 24-hour ambulatory BP, and BP variability (BPV) in treatment-naïve patients with systolic hypertension using lercanidipine for stage 1 and lercanidipine/enalapril for stage 2. Patients and methods: This was an open-label, prospective interventional study conducted in 22 general practices in South Africa. Treatment-naïve patients with stage 1 hypertension received lercanidipine 10 mg and patients with stage 2 received lercanidipine 10 mg/enalapril 10 mg. After 6 weeks, patients not reaching target (

Olga K Lutzko,1 Helen Schifferle,2 Marita Ariola,3 Antonia Rich,4 Khen Meng Kon5 1Kardinia Health, GP Super Clinic, Belmont, VIC, 2Medicross Rothwell, Rothwell, QLD, 3Innerwest Specialist Centre, Burwood, NSW, Australia; 4Atlantis Healthcare Pty Ltd, Sydney, Australia; 5Sanofi Australia Pty Ltd, Macquarie Park, NSW, Australia Purpose: The purpose of this study was to evaluate the optimization of fasting blood glucose (FBG) levels in patients with type 2 diabetes mellitus newly initiated on insulin glargine who were enrolled in the Australian Diabetes CoStars Patient Support Program (PSP). Patients and methods: A retrospective analysis of data from 514 patients with type 2 diabetes mellitus who completed the 12-week Diabetes CoStars PSP was performed. All patients were initiated on insulin glargine in primary care and enrolled by their general practitioner, who selected a predefined titration plan and support from a local Credentialled Diabetes Educator. The data collected included initial and final insulin dose, self-reported FBG, and glycated hemoglobin (A1c) levels. Results: The insulin dose increased in 81% of patients. Mean FBG was reduced from 208.8 mg/dL (11.6 mmol/L) to 136.8 mg/dL (7.6 mmol/L) after 12 weeks. Initial and final A1c values were available for 99 patients; mean A1c was reduced from 9.5% (80 mmol/mol) to 8.1% (65 mmol/mol). The reductions in mean FBG and A1c were similar irrespective of titration plan. Overall, 27.2% of patients achieved FBG levels within the titration plan target range of 72–108 mg/dL (4–6 mmol/L) and an additional 43.4% of patients achieved FBG within the range recommended by current Australian guidelines (110–144 mg/dL [6.1–8.0 mmol/L]). Overall, 23.3% of patients achieved the A1c target of ≤7%. Conclusion: These data demonstrate that the majority of patients enrolled in the Diabetes CoStars PSP achieved acceptable FBG levels 12 weeks after starting insulin therapy irrespective of titration plan. Keywords: insulin glargine, titration, type 2 diabetes mellitus, fasting blood glucose