Development of a real-world database for asthma and COPD: The SingHealth-Duke-NUS-GSK COPD and Asthma Real-World Evidence (SDG-CARE) collaboration.

PURPOSE: The SingHealth-Duke-GlaxoSmithKline COPD and Asthma Real-world Evidence (SDG-CARE) collaboration was formed to accelerate the use of Singaporean real-world evidence in research and clinical care. A centerpiece of the collaboration was to develop a near real-time database from clinical and operational data sources to inform healthcare decision making and research studies on asthma and chronic obstructive pulmonary disease (COPD). METHODS: Our multidisciplinary team, including clinicians, epidemiologists, data scientists, medical informaticians and IT engineers, adopted the hybrid waterfall-agile project management methodology to develop the SingHealth COPD and Asthma Data Mart (SCDM). The SCDM was developed within the organizational data warehouse. It pulls and maps data from various information systems using extract, transform and load (ETL) pipelines. Robust user testing and data verification was also performed to ensure that the business requirements were met and that the ETL pipelines were valid. RESULTS: The SCDM includes 199 data elements relevant to asthma and COPD. Data verification was performed and found the SCDM to be reliable. As of December 31, 2019, the SCDM contained 36,407 unique patients with asthma and COPD across the spectrum from primary to tertiary care in our healthcare system. The database updates weekly to add new data of existing patients and to include new patients who fulfil the inclusion criteria. CONCLUSIONS: The SCDM was systematically developed and tested to support the use RWD for clinical and health services research in asthma and COPD. This can serve as a platform to provide research and operational insights to improve the care delivered to our patients.

Treatment patterns and cost of exacerbations in patients with chronic obstructive pulmonary disease using multiple inhaler triple therapy in South Korea.

BACKGROUND: Multiple inhaler triple therapy (MITT), comprising inhaled corticosteroids (ICS), long-acting beta-agonists (LABA), and long-acting muscarinic antagonists (LAMA), has been used as an escalation treatment for patients with chronic obstructive pulmonary disease (COPD). However, real-world use of MITT has not been investigated in Asia, including South Korea. This study reports baseline characteristics of patients with COPD initiated on MITT in South Korea, and their treatment patterns. Healthcare resource utilization (HRU) and costs associated with COPD exacerbations following MITT initiation were also assessed. METHODS: This was a retrospective cohort study using the South Korea National Health Insurance database (2014-2018). Included patients were ≥ 40 years, had a COPD diagnosis, were newly initiated on MITT and had ≥ 12 months' data both before (baseline) and after index date (the first day with overlapping supply of all MITT components). Treatment immediately before initiation and immediately following discontinuation of MITT were identified, and proportion of days covered (PDC) by MITT was calculated. HRU and costs (per person per year [PPPY]) associated with exacerbations were identified following MITT initiation; costs were calculated using the average 2020 exchange rate (0.0008 USD/KRW). RESULTS: Among 37,400 patients, the mean age was 69 (SD 10) years and 73% were males; 56% had ≥ 1 COPD exacerbation during the baseline period, with a mean of 2 (SD 5) events/year. ICS/LABA was the most frequent regimen prescribed immediately before initiation (37%) and immediately following discontinuation (41% of 34,264 patients) of MITT. At 3, 6, and 12 months from treatment initiation, mean PDC was 81%, 63% and 49%, respectively; median treatment duration was 102 days. The mean (95% confidence interval [CI]) number of total visits for severe COPD exacerbations was 0.77 PPPY (0.75-0.78); mean PPPY total healthcare costs were 2093 USD. CONCLUSIONS: Patients with COPD in South Korea experienced frequent exacerbations prior to MITT, and PDC by MITT was low. Patients may benefit from early optimization of COPD therapy, and greater emphasis on adherence to inhaled COPD therapy. Severe exacerbations were found to incur substantial costs; treatment alternatives that can reduce the rate of severe exacerbations are likely to minimize healthcare costs.

Long-Acting Bronchodilator Use in Chronic Obstructive Pulmonary Disease in Primary Care in New Zealand: A Retrospective Study of Treatment Patterns and Evolution Using the HealthStat Database.

PURPOSE: 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 ß2-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.

Temporal Trends and Patient Characteristics Associated With Drug Utilisation After First-Ever Stroke: Insights From Chronic Disease Registry Data in Singapore.

INTRODUCTION: Data on drug utilisation among stroke patients of Asian ethnicities are lacking. The objectives of the study were to examine the temporal trends and patient characteristics associated with prescription of thrombolytic, antithrombotic and statin medications among patients with first-ever stroke. MATERIALS AND METHODS: First-ever ischaemic and haemorrhagic stroke patients admitted to 2 Singapore tertiary hospitals between 2010‒2014 were included. Data were extracted from the National Healthcare Group Chronic Disease Management System. Association between drug utilisation and admission year, as well as characteristics associated with drug use, were explored using multivariable logistic regression. RESULTS: There was an increasing trend in the combined use of all 3 guideline medications in ischaemic stroke patients (P <0.001)-specifically thrombolytic agents (P <0.001), oral antithrombotics (P = 0.002) and statins (P = 0.003) at discharge. Among antithrombotics, the use of clopidogrel (P <0.001) and aspirin-clopidogrel (P <0.001) had increased, whereas prescription of dipyridamole (P <0.001) and aspirin-dipyridamole (P <0.001) had declined. For statins, the increase in atorvastatin prescription (P <0.001) was accompanied by decreasing use of simvastatin (P <0.001). Age, ethnicity and certain comorbidities (hyperlipidaemia, atrial fibrillation and chronic kidney disease) were associated with the combined use of all 3 guideline medications (P <0.05). In haemorrhagic stroke, prescription of statins at discharge were comparatively lower. CONCLUSION: This study reveals changes in prescription behaviour over time in a multiethnic Asian population with first-ever stroke. Patient characteristics including younger age, Malay ethnicity and certain comorbidities (i.e. hyperlipidaemia, atrial fibrillation) were associated with the combined use of all 3 guideline medications among ischaemic stroke patients.

Impact of medication nonadherence on stroke recurrence and mortality in patients after first-ever ischemic stroke: Insights from registry data in Singapore.

PURPOSE: This retrospective cohort study aims to examine adherence to secondary stroke preventive medications and their association with risk of stroke recurrence and mortality in patients after first-ever ischemic stroke. METHODS: Using data from the National Healthcare Group and Singapore Stroke Registry, patients with first-ever ischemic stroke between 2010 and 2014 were included, and categorized based on antithrombotic or statin adherence using the proportion of days covered: high (≥75%), intermediate (50%-74%), low (25%-49%), and very low (<25%). The primary outcome was first recurrent ischemic stroke within a year after hospital discharge, while the secondary composite outcomes were (a) stroke recurrence and all-cause mortality and (b) stroke recurrence and cardiovascular mortality. The Cox proportional hazard model was used to examine the association between medication adherence and outcomes. Adjusted hazard ratios (aHRs) and the corresponding 95% confidence intervals (CIs) were reported. RESULTS: Among ischemic stroke patients prescribed with antithrombotics (n = 1139) or statins (n = 1160) at hospital discharge, about one-third were highly adherent to their medications. Patients with lower medication adherence tended to be younger, were admitted to private ward classes, and were without hypertension. Compared with the patients with high medication adherence, the risk of stroke recurrence was higher in patients with very low antithrombotic (aHR = 4.65; 95% CI: 1.45-14.89) or statin (aHR = 3.44; 95% CI: 0.93-12.74) adherence. Similar findings were observed for the secondary outcomes. CONCLUSIONS: Poor adherence to antithrombotic and statin treatment increases the risk of recurrent stroke and mortality in patients after first-ever ischemic stroke. Further measures are needed to improve medication adherence among stroke survivors.

Use of Selective Serotonin Reuptake Inhibitors and Outcomes in Stroke Rehabilitation: A Prospective Observational Pilot Cohort Study.

PURPOSE: The aim of this study was to examine the association between selective serotonin reuptake inhibitor (SSRI) therapy and rehabilitation outcomes, specifically disability and quality of life (QOL), in a real-world setting of multi-ethnic Asian patients with first-ever stroke. METHODS: In this prospective observational pilot cohort study, we included patients with first-ever stroke admitted to two inpatient rehabilitation centres in Singapore between January and July 2018. Outcomes were measured using Functional Independence Measure (FIM)-motor scale, modified Barthel Index (MBI) and the Stroke and Aphasia Quality of Life Scale-39 generic (SAQOL-39g) questionnaire. Linear regression was used to assess the association between SSRI therapy and outcomes. Regression coefficients and 95% confidence intervals (CIs) were reported. RESULTS: Among 57 patients included for analyses, 38.6% received SSRIs. Although SSRI therapy was significantly associated with gains in MBI (coefficient 11.35; 95% CI 0.21-22.50) and SAQOL-39g overall score (coefficient 0.45; 95% CI 0.05-0.85) based on simple linear regression, no significant association between SSRI therapy and any of the investigated outcomes was found after adjustment for confounders. However, an increase in the mean number of physiotherapy and occupational therapy (PT/OT) sessions per day significantly improved FIM-motor (coefficient 16.86; 95% CI 2.64-31.07) and MBI (coefficient 22.79; 95% CI 2.35-43.23) scores. CONCLUSION: SSRI therapy did not improve disability and QOL in multi-ethnic Asian patients with first-ever stroke undergoing rehabilitation.

Temporal Trends and Predictors of Drug Utilization and Outcomes in First-Ever Stroke Patients: A Population-Based Study Using the Singapore Stroke Registry.

INTRODUCTION: Drug utilization and outcomes research in multi-ethnic Asian stroke populations is lacking. OBJECTIVES: Our objective was to examine temporal trends and predictors of drug utilization and outcomes in a multi-ethnic Asian stroke population. METHODS: This registry-based study included ischemic and hemorrhagic first-ever stroke patients hospitalized between 2009 and 2016. Utilization of medications included in-hospital thrombolytic agents, early antithrombotics (antiplatelets, anticoagulants) within 48 h of admission, and antithrombotics and statins at discharge. Outcomes analyzed were in-hospital all-cause mortality; 28-day, 90-day, and 1-year case fatality (CF); and discharge destination. RESULTS: Of the 36,615 included patients, 81.6% had ischemic stroke and 18.4% had hemorrhagic stroke (15.5% intracerebral hemorrhage [ICH] and 2.8% subarachnoid hemorrhage [SAH]). For ischemic stroke, the combined use of all three guideline medications (in-hospital thrombolytic therapy, as well as antithrombotics and statins at discharge) increased (P = 0.006). Being on the stroke pathway was associated with prescription of all three guideline medications in ischemic stroke. Decreasing trends for in-hospital mortality, 28-day, 90-day, and 1-year CF and proportion of patients discharged home without rehabilitation appointment were observed in ischemic stroke (P < 0.05) but not in ICH or SAH (apart from 28-day CF). Ischemic stroke patients who received guideline medications were less likely to die or be discharged to nursing homes and chronic sick hospitals. Hemorrhagic stroke patients prescribed statins at discharge were less likely to have 28-day and 1-year CF. CONCLUSIONS: Prescription of secondary stroke preventive medications (particularly in ischemic stroke) was associated with more favorable outcomes, highlighting the importance of physician adherence to evidence-based pharmacotherapy.

Efficacy and safety of inhaled corticosteroids relative to fluticasone propionate: a systematic review of randomized controlled trials in asthma.

INTRODUCTION: Many trials have been published comparing inhaled corticosteroid (ICS) treatments in asthma. However, mixed results necessitate the summarization of available evidence to aid in decision-making. Areas covered: This systematic review evaluated randomized controlled trials (RCTs) that compared the efficacy and safety of inhaled fluticasone propionate (FP) with other ICS including beclomethasone dipropionate (BDP), budesonide (BUD) and ciclesonide (CIC). PubMed was searched and 54 RCTs that fit pre-determined criteria were included. Endpoints evaluated included lung function, asthma symptom control, exacerbation frequency, reliever use, quality of life and steroid-related side effects. Expert commentary: Across all studies, FP was associated with either more favorable or at least similar efficacy and safety, in comparison with BDP or BUD. This observation may be related to FP's higher relative potency and almost negligible oral bioavailability. FP was comparable to CIC for efficacy. However, CIC appeared to have a smaller impact on cortisol levels than FP, which is likely due to CIC's incomplete conversion to active metabolite (des-CIC) and the lower potency of des-CIC compared with FP. Although there were no significant differences in evaluated outcomes after treatment with different ICS in the majority of studies, some observed differences could be explained by their respective pharmacodynamic and pharmacokinetic properties.

Effects of Central Nervous System Drugs on Recovery After Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND AND OBJECTIVE: Pilot trials have suggested that pharmacotherapy may aid stroke recovery. The aim of this study was to systematically review the effects of antidepressants, anti-Alzheimer drugs, anti-Parkinson drugs, central nervous system (CNS) stimulants and piracetam on gross motor function, cognition, disability, dependency and quality of life (QOL) after stroke. METHODS: PubMed, EMBASE and the Cochrane Central Register of Controlled Trials databases were searched, and 44 randomized controlled trials that compared outcomes of interest between drug treatment and placebo or no treatment were included. For each study, standardized mean difference (SMD) or mean difference (MD) with 95% confidence interval (CI) were calculated. Meta-analyses were conducted to pool results using either the fixed-effects or random-effects model. RESULTS: Selective serotonin reuptake inhibitors (SSRIs) improved gross motor function (SMD 0.54, 95% CI 0.22-0.85; three studies), disability (SMD 0.49, 95% CI 0.32-0.66; 14 studies) and QOL (MD 6.46, 95% CI 4.71-8.22; two studies), but there was insufficient evidence for their use in enhancing global cognition (SMD 0.23, 95% CI -0.01 to 0.46; five studies) and dependency (risk ratio 0.81, 95% CI 0.68-0.97; one fluoxetine study). In particular, gross motor function was improved by fluoxetine (SMD 0.64, 95% CI 0.31-0.98; two studies), while disability was improved by paroxetine (SMD 1.05, 95% CI 0.63-1.46; two studies), citalopram (SMD 0.51, 95% CI 0.08-0.93; two studies) and fluoxetine (SMD 0.41, 95% CI 0.22-0.60; nine studies). There is insufficient evidence for the use of anti-Alzheimer drugs, anti-Parkinson drugs, CNS stimulants and piracetam to promote stroke recovery. CONCLUSIONS: Administration of SSRIs may improve gross motor function, reduce disability and enhance QOL for patients recovering from stroke.