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Marcus Sim,1 Anthony Yii,1 Xiaomeng Xu,2 Priti Bahety,3 Chee Hong Loh,1 Aldo Amador Navarro Rojas,4 Dominique Milea,2 Augustine Tee1 1Department of Respiratory and Critical Care Medicine, Changi General Hospital, Singapore, Singapore; 2Value Evidence & Outcomes, Greater China and Intercontinental, GSK, Singapore, Singapore; 3Medical Affairs, GSK, Singapore, Singapore; 4Respiratory & Specialty Medical Lead, Greater China and Intercontinental, GSK, Singapore, SingaporeCorrespondence: Marcus Sim, Department of Respiratory and Critical Care Medicine, Changi General Hospital, 2 Simei Street 3, Singapore, 529889, Singapore, Tel +65 6788 8833, Email marcus.sim@mohh.com.sgIntroduction: There is limited real-world evidence regarding clinical practice for chronic obstructive pulmonary disease (COPD) in Singapore. We compared baseline clinical characteristics and evaluated outcomes in patients with COPD who initiated treatment with either a long-acting muscarinic antagonist (LAMA) or a LAMA and a long-acting β2-agonist (LAMA+LABA).Methods: This was a single-center observational study at Changi General Hospital, Singapore. Routine clinical data (hospital visits, case management, lung function, laboratory/imaging results, medication orders) were collected and compiled into a data warehouse. Eligible patients with COPD were ≥ 40 years old and newly prescribed LAMA or LAMA+LABA during the enrollment period. Patient characteristics in the baseline period (6 months) were compared between treatments. Clinical worsening was measured as a composite endpoint, defined as the first of a change in maintenance treatment class or a moderate-to-severe exacerbation during follow-up (12 months).Results: In total, 261 patients were included in the baseline period (LAMA: 73; LAMA+LABA: 188). In the baseline period, patients receiving LAMA+LABA versus LAMA had significantly lower body mass index, higher COPD Assessment Test score and worse lung function, and numerically higher exacerbation history. Prevalence of comorbidities was similar between treatment groups. In follow-up, high rates of clinical worsening were observed regardless of treatment regimen (LAMA: 38/73 [52%]; LAMA+LABA: 86/188 [46%]). Median time-to-clinical worsening was 340 days for the LAMA cohort and the raw median 154 days (interquartile range: 44– 225) for the LAMA+LABA cohort. Median medication dispensation rate (0.86; interquartile range: 0.56– 1.00) was similar between treatments.Conclusion: Patients initiating treatment with LAMA+LABA had more severe COPD than patients prescribed LAMA. The proportion of patients experiencing clinical worsening was similarly high in both cohorts, suggesting that early identification and treatment optimization are necessary.Keywords: COPD treatment, database analysis, dual bronchodilator, LABA, LAMA, inhaler prescription

Xian Hui Lim,1 Monisha Esther Nongpiur,1– 3 Raymond P Najjar,2,3 Quan V Hoang,1– 4 Dan Milea,1– 3 Chee Wai Wong,1– 3 Rahat Husain,1,3 Hla Myint Htoon,2,3 Tin Aung,1– 3,5 Shamira Perera,1– 3 Tina Tzee Ling Wong1– 3,5 1Singapore National Eye Centre, Singapore; 2Singapore Eye Research Institute, Singapore; 3Duke-NUS Medical School, Singapore; 4Department of Ophthalmology, Edward S. Harkness Eye Institute, Columbia College of Physicians and Surgeons, New York, NY, USA; 5Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, SingaporeCorrespondence: Tina Tzee Ling WongSingapore National Eye Centre, 11 Third Hospital Avenue, 168751, SingaporeEmail tina.wong.t.l@singhealth.com.sgPurpose: To investigate features of the steady-state pattern electroretinogram (ssPERG) in subjects with glaucoma (G), high myopia (HM; spherical equivalent ≤-6D) and glaucoma with high myopia (GHM).Patients and Methods: Our study included 48 participants divided into 3 groups (G, HM, and GHM) who each underwent monocular ssPERG testing with Diopsys NOVA PERG protocols. The ConStim protocol detects distinct topographic patterns of dysfunction 16° and 24° around the central macula. MagD is the amplitude of the average signal and MagD/Mag ratio indicates the consistency of the response. ssPERG indices were compared between groups and correlated with functional (ie, visual field mean deviation (VFMD)) and structural (ie, average retinal nerve fibre layer (RNFL) thickness; Cirrus optical coherence tomography) features.Results: Participants had an average age of 59.4± 7.6 years. Mean Humphrey VFMD was − 14.22 ± 2.88dB, − 2.62 ± 1.18dB and − 12.80 ± 2.60dB for G, HM and GHM groups, respectively. Mean RNFL thickness was 63.0 ± 8.20μm, 69.5 ± 15.7μm and 60.6 ± 5.0μm for G, HM and GHM groups, respectively. For the 24° setting, no significant differences were noted for any of the parameters. For the 16° setting, MagD was lower in the GHM group compared to the HM group (0.29μV vs 0.52μV; p = 0.02). Significant differences were noted for the MagD/Mag ratio between HM and G groups (0.58 vs 0.40; p = 0.02) and between HM and GHM groups (0.58 vs 0.35; p = 0.002). There were positive correlations between both MagD 16° and MagD/Mag ratio 16° with VFMD (correlation coefficient [r]=0.37, p = 0.009; and r = 0.44, p = 0.002, respectively) and RNFL (r = 0.43, p = 0.002; and r = 0.48, p = 0.001, respectively).Conclusion: MagD/Mag ratio at 16° was significantly lower in glaucomatous eyes (with or without high myopia) compared to those with high myopia without glaucoma, suggesting that glaucoma has a distinct impact on MagD/Mag ratio at 16° irrespective of the presence of myopia.Keywords: pattern electroretinogram, visual field mean deviation, optical coherence tomography, retinal nerve fibre layer

Dominique Milea,1 See-Hwee Yeo,1 Yein Nam,2 Aldo Amador Navarro Rojas,1 Sumitra Shantakumar,1 Janine Beale,3 Brett Marett,3 Robert P Young,4 Raewyn J Scott,4 Barry Gribben5 1Value Evidence and Outcomes, GlaxoSmithKline plc., Greater China and Intercontinental, 139234, Singapore; 2Real World Evidence & Epidemiology, Adelphi Real World, Macclesfield, Cheshire, UK; 3Medical Affairs, GlaxoSmithKline plc., Auckland, New Zealand; 4Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand; 5Public Sector Surveying, CBG Health Research Limited, Auckland, New ZealandCorrespondence: Dominique MileaValue Evidence and Outcomes, GlaxoSmithKline plc., Greater China and Intercontinental, 23 Rochester Park, 139234, SingaporeTel +65 9830 7891Email dominique.x.milea@gsk.comPurpose: Long-acting bronchodilator (LABD) use is the mainstay of pharmacologic treatment for chronic obstructive pulmonary disease (COPD). Few studies describe evolving patterns of LABD use in the setting of changing inhaler availability and updated clinical guidelines.Methods: A retrospective cohort study in New Zealand using the HealthStat general practice database (01/2014 to 04/2018). Eligible patients (aged ≥ 40 years) had COPD and ≥ 1 LABD prescription (long-acting muscarinic antagonist [LAMA] and/or long-acting β2-agonist [LABA]) during the index period (05/2015 to 04/2016). Demographics and clinical characteristics of all LABD users (overall/by treatment) were described at baseline. Patients starting LABD treatment during the index period, termed “new” users, were also described, as was their treatment evolution over 24 months of follow-up. Yearly LABD initiation rates were assessed from 2015 to 2017, covering changes to Pharmaceutical Management Agency criteria and clinical guidelines.Results: Across 2140 eligible patients, the most common index treatments were inhaled corticosteroid (ICS)/LABA (59.0%) and open triple therapy (LAMA+LABA+ICS; 26.7%). ICS/LABA therapy was highest in younger patients, with open triple therapy highest in older patients. Prior yearly exacerbation rates were lowest in those receiving monotherapy (LABA: 0.9/year; LAMA: 1.1/year) versus dual therapy (all 1.4/year) and open triple therapy (2.2/year). Of 312 new LABD users, ICS/LABA was the most common index treatment (69.6%), followed by LAMA monotherapy (16.0%). Continuous use with index treatment was 31.1% at 12 months and 13.5% at 24 months; mean time to treatment change was 175.5 and 244.1 days, respectively. Among patients modifying treatment at 24 months, 23.0% augmented, 7.0% switched, 45.6% re-started, and 24.4% discontinued/stepped down. Among patients initiating LABD each year from 2015 to 2017, LAMA prescription increased (17% to 46%) while ICS prescription remained stable (approximately 20%).Conclusion: Predominant use of ICS/LABA (05/2015 to 04/2016) reflects available LABDs and previous restrictions on LAMA use in New Zealand.Keywords: bronchodilator therapy, chronic obstructive pulmonary disease, long-acting muscarinic antagonist, long-acting β2-agonist, inhaled corticosteroid, New Zealand

Jin Rong Low,1– 3 Chee Wai Wong,1,3– 6 Jing Liang Loo,1,3,5– 8 Dan Milea,3,5,7,8 Shamira A Perera,1– 3,5 Yi Fang Lee,3,9 Si Rui Ng,1– 3 Mani Baskaran,2,3,5 Monisha Esther Nongpiur,2,3,5 Sharon Lee Choon Tow1,3,5– 8 1Department of Cataract and Comprehensive Ophthalmology, Singapore National Eye Centre, Singapore; 2Department of Glaucoma, Singapore National Eye Centre, Singapore; 3Singapore Eye Research Institute, Singapore; 4Department of Surgical Retina, Singapore National Eye Centre, Singapore; 5Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore; 6Department of Ophthalmology, National University of Singapore, Singapore; 7Department of Neuro-Ophthalmology, Singapore National Eye Centre, Singapore; 8Neuroscience and Behavioral Disorders Program, Duke-NUS Medical School, Singapore; 9Department of Training and Education, Singapore National Eye Centre, SingaporeCorrespondence: Sharon Lee Choon Tow Tel +65 6322 7443Fax +65 6333 8339Email sharon.tow.l.c@singhealth.com.sgPurpose: The aim of the study is to examine the baseline intraocular pressure (IOP) and its changes after performing a water drinking test (WDT) in patients with unilateral hemifacial spasm (HFS).Patients and Methods: In this prospective observational study, patients aged 21 years and above diagnosed with unilateral HFS were recruited from the Singapore National Eye Centre between January 2015 and August 2016. The unaffected eye of each patient served as a matched control. An interviewer-administered standardized questionnaire on HFS symptoms and ophthalmic examination was performed. Automated perimetry, optical coherence tomography (OCT) of the optic nerve head, color disc stereophotography and water drinking test (WDT) were done. The primary outcome measure was the difference in IOP between eyes affected by HFS and fellow eyes at baseline and at 15, 30 and 45 minutes of the WDT.Results: Fifty-four patients with unilateral HFS were included. Mean age was 59.8± 9.9 years (range, 37.0– 84.0). Of these, 54% were female and 94% were Chinese. Mean baseline IOP was significantly higher in eyes with HFS (13.9± 3.1mmHg) compared to fellow eyes (13.3± 2.8mmHg) (p=0.008). There was no significant difference in absolute or percentage change in IOP from baseline between the 2 groups at 15, 30 and 45 minutes of the WDT. Mean vertical cup–disc ratio (VCDR) on clinical examination was significantly higher in eyes with HFS (0.5± 0.2) compared to fellow eyes (0.4± 0.2) (p=0.02). There was no significant difference between the groups for visual field parameters and mean retinal nerve fiber layer thickness on OCT.Conclusion: Hemifacial spasm is associated with a small but significant difference in mean baseline IOP and VCDR between affected and fellow eyes. However, when eyes affected by HFS and fellow eyes were challenged with the WDT, both responded in similar ways.Keywords: glaucoma, hemifacial spasm, intraocular pressure, water drinking test

Lene Hammer-Helmich,1 Josep Maria Haro,2 Bengt Jönsson,3 Audrey Tanguy Melac,4 Sylvie Di Nicola,5 Julien Chollet,6 Dominique Milea,7 Benoît Rive,8 Delphine Saragoussi4 1Real World Evidence and Epidemiology, H Lundbeck A/S, Valby, Denmark; 2Research and Teaching Unit, Parc Sanitari Sant Joan de Deu, CIBERSAM, University of Barcelona, Barcelona, Spain; 3Department of Economics, Stockholm School of Economics, Stockholm, Sweden; 4Real-World Evidence and Epidemiology, Lundbeck SAS, Issy-les-Moulineaux, 5Biostatistics, Inferential, Paris, 6Clinical Operations, Lundbeck SAS, Issy-les-Moulineaux, France; 7Health Economics and Epidemiology, Lundbeck Singapore Pte. Ltd, Singapore, Singapore; 8Global Analytics, Lundbeck SAS, Issy-les-Moulineaux, France Background: The Prospective Epidemiological Research on Functioning Outcomes Related to Major depressive disorder (PERFORM) study describes the course of depressive symptoms, perceived cognitive symptoms, and functional impairment over 2 years in outpatients with major depressive disorder (MDD) and investigates the patient-related factors associated with functional impairment.Methods: This was a 2-year observational study in 1,159 outpatients with MDD aged 18–65 years who were either initiating antidepressant monotherapy or undergoing their first switch of antidepressant. Functional impairment was assessed by the Sheehan Disability Scale and the Work Productivity and Activity Impairment questionnaire. Patients assessed depression severity using the nine-item Patient Health Questionnaire and severity of perceived cognitive symptoms using the five-item Perceived Deficit Questionnaire. To investigate which patient-related factors were associated with functional impairment, univariate analyses of variance were performed to identify relevant factors that were then included in multivariate analyses of covariance at baseline, month 2, months 6 and 12 combined, and months 18 and 24 combined.Results: The greatest improvement in depressive symptoms, perceived cognitive symptoms, and functional impairment was seen immediately (within 2 months) following initiation or switch of antidepressant therapy, followed by more gradual improvement and long-term stabilization. Improvement in perceived cognitive symptoms was less marked than improvement in depressive symptoms during the acute treatment phase. Functional impairment in patients with MDD was not only associated with severity of depressive symptoms but also independently associated with severity of perceived cognitive symptoms when adjusted for depression severity throughout the 2 years of follow-up.Conclusion: These findings highlight the burden of functional impairment in MDD and the importance of recognizing and managing cognitive symptoms in daily practice. Keywords: major depressive disorder, functioning, functional impairment, depression, cognition

Purpose: Real-world data on maintenance treatment and prescription patterns provide insights into healthcare management among patients with chronic obstructive pulmonary disease (COPD), which benefits our understanding of current COPD treatment patterns in New Zealand., Methods: We retrospectively analyzed real-world data from the HealthStat general practice database to evaluate treatment patterns among patients with COPD in New Zealand who initiated multiple-inhaler triple therapy (MITT): inhaled corticosteroid (ICS) + long-acting muscarinic antagonist + long-acting β 2 -agonist (LABA). Our main objective described treatment patterns (class, duration, modification, persistence, and adherence) and characteristics of patients with COPD initiating MITT between 1 May 2016 and 30 April 2017, with 12-months' follow-up. We also assessed the number of patients receiving MITT between 2015 and 2017, among a larger patient population receiving long-acting bronchodilator and ICS-containing therapies., Results: Of 6249 eligible patients, 421 (mean age 67.3 years; mean number exacerbations at baseline 1.8) initiated MITT: 59.1% received combination ICS/LABA therapy prior to MITT initiation, and median treatment duration prior to MITT initiation was 350 days. Overall, 33.5% of patients remained on index treatment for 12 months. Of the remaining patients who modified treatment (on average at 144.4 days), those who had a direct switch (24.9%) or retreatment (13.5%) remained on MITT, 19.7% of patients stepped down to mono/dual therapy, and 8.3% discontinued treatment. Mean (standard deviation) persistence to any MITT over 12 months was 47.3 (50.0), and 53.4% of patients were considered adherent to MITT. Total proportions of patients receiving long-acting bronchodilator therapy and MITT increased between 2015 and 2017., Conclusion: Most patients with COPD in New Zealand who initiated MITT had characteristics appropriate for triple therapy prescription, suggesting prescription behavior among general practitioners was largely consistent with treatment guidelines. Our findings may help optimize treatment decisions, with a focus on improving long-term triple therapy persistence and adherence., Competing Interests: XX received funding from GlaxoSmithKline plc. (through GMP Technologies PTE Ltd.) to conduct this study. DM, AANR, AB, and BM are employees of, and shareholders in, GlaxoSmithKline plc. TH is an employee of Adelphi Real World, who received funding from GlaxoSmithKline plc. to conduct this study. RY and RJS have received honorarium from GlaxoSmithKline plc. for educational talks and participation in advisory groups. BG is an employee of, shareholder in, and receives funding for project management and analysis from CBG Health Research Ltd, and is also a shareholder in HealthStat who received funding for data collection from GlaxoSmithKline plc. to conduct this study. Trademarks are owned by or licensed to their respective owners. The authors report no other conflicts of interest in this work., (© 2021 Xu et al.)