Approach to headache disorders and the management of migraine: consensus guidelines from the Headache Society of Singapore, first edition (2023).

Headache disorders, particularly migraine, are one of the most common and disabling neurological disorders. There is a need for high-quality, accessible care for patients with headache disorders across all levels of the healthcare system in Singapore. The role of the Headache Society of Singapore is to increase awareness and advance the understanding of these disorders and to advocate for the needs of affected patients. In this first edition of local consensus guidelines, we focus on treatment approaches for headaches and provide consensus recommendations for the management of migraine in adults. The recommendations in these guidelines can be used as a practical tool in routine clinical practice by primary care physicians, neurologists and other healthcare professionals who have a common interest in headache disorders.

Genotype-guided versus traditional clinical dosing of warfarin in patients of Asian ancestry: a randomized controlled trial.

BACKGROUND: Genotype-guided warfarin dosing has been shown in some randomized trials to improve anticoagulation outcomes in individuals of European ancestry, yet its utility in Asian patients remains unresolved. METHODS: An open-label, non-inferiority, 1:1 randomized trial was conducted at three academic hospitals in South East Asia, involving 322 ethnically diverse patients newly indicated for warfarin (NCT00700895). Clinical follow-up was 90 days. The primary efficacy measure was the number of dose titrations within the first 2 weeks of therapy, with a mean non-inferiority margin of 0.5 over the first 14 days of therapy. RESULTS: Among 322 randomized patients, 269 were evaluable for the primary endpoint. Compared with traditional dosing, the genotype-guided group required fewer dose titrations during the first 2 weeks (1.77 vs. 2.93, difference -1.16, 90% CI -1.48 to -0.84, P < 0.001 for both non-inferiority and superiority). The percentage of time within the therapeutic range over 3 months and median time to stable international normalized ratio (INR) did not differ between the genotype-guided and traditional dosing groups. The frequency of dose titrations (incidence rate ratio 0.76, 95% CI 0.67 to 0.86, P = 0.001), but not frequency of INR measurements, was lower at 1, 2, and 3 months in the genotype-guided group. The proportions of patients who experienced minor or major bleeding, recurrent venous thromboembolism, or out-of-range INR did not differ between both arms. For predicting maintenance doses, the pharmacogenetic algorithm achieved an R2 = 42.4% (P < 0.001) and mean percentage error of -7.4%. CONCLUSIONS: Among Asian adults commencing warfarin therapy, a pharmacogenetic algorithm meets criteria for both non-inferiority and superiority in reducing dose titrations compared with a traditional dosing approach, and performs well in prediction of actual maintenance doses. These findings imply that clinicians may consider applying a pharmacogenetic algorithm to personalize initial warfarin dosages in Asian patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT00700895 . Registered on June 19, 2008.

Cost-Effectiveness Analysis of Ticagrelor and Prasugrel for the Treatment of Acute Coronary Syndrome.

BACKGROUND: In the management of Asian patients with acute coronary syndrome (ACS), the comparative cost-effectiveness of ticagrelor and prasugrel, referenced to generic clopidogrel, is unknown. OBJECTIVE: To assess the cost-effectiveness of ticagrelor and prasugrel as compared with generic clopidogrel in patients with ACS in Singapore. METHODS: A Markov model simulating a typical cohort of 62-year-old patients with ACS was constructed from a patient's perspective over a lifetime horizon. Treatment effects and adverse events, including nonfatal myocardial infarction, major bleeding related to non-coronary artery bypass grafting, dyspnea, or death, were estimated from pivotal trials comparing clopidogrel with ticagrelor and prasugrel, respectively. Costs were estimated from a tertiary hospital with more than 1500 admissions for ACS per year. RESULTS: The incremental cost-effectiveness ratio (ICER) per life-year gained for ticagrelor was about three times more favorable than for prasugrel (Singapore dollar [SGD] 13,276 vs. SGD 38,809). The ICER per quality-adjusted life-year (QALY) for prasugrel and ticagrelor, however, was comparable at SGD 18,921 and SGD 18,647, respectively. Deterministic sensitivity analysis revealed that the ICER per QALY gained for prasugrel and ticagrelor was most sensitive to the hazard ratio of all-cause mortality and utility for dyspnea, respectively. Probabilistic sensitivity analysis demonstrated that compared with clopidogrel, the probabilities of prasugrel and ticagrelor being cost-effective are 87.1% and 88.3% based on the willingness-to-pay value of SGD 65,000 (one time the gross domestic product per capita in Singapore). CONCLUSIONS: Ticagrelor is more cost-effective than prasugrel in reducing all-cause mortality in patients with ACS. The cost-effectiveness of ticagrelor and prasugrel become similar, however, when accounting for the impact of dyspnea on QALY.

Comparative efficacy and tolerability of topical prostaglandin analogues for primary open-angle glaucoma and ocular hypertension.

OBJECTIVE: To systematically review the efficacy and tolerability of 4 prostaglandin analogues (PGAs) as first-line monotherapies for intraocular pressure (IOP) lowering in adult patients with primary open-angle glaucoma or ocular hypertension. DATA SOURCES: A literature search was performed in PubMed (1965-June 2013) and the Cochrane Library (1980-June 2013) using the search terms ocular hypertension, open-angle glaucoma, prostaglandin analogues, bimatoprost, latanoprost, tafluprost, and travoprost. Additional studies were searched from the reference lists of identified publications. STUDY SELECTION AND DATA EXTRACTION: In all, 32 randomized controlled trials comparing between PGAs (bimatoprost 0.03%, latanoprost 0.005%, tafluprost 0.0015%, and travoprost 0.004%) or PGA with timolol were selected. DATA SYNTHESIS: A network meta-analysis was conducted. Using timolol as reference, the relative risks (RRs) of achieving treatment success, defined as the proportion of patients achieving at least 30% IOP reduction, with 95% CIs, were as follows: bimatoprost, 1.59 (1.28-1.98); latanoprost, 1.32 (1.00-1.74); travoprost, 1.33 (1.03-1.72); and tafluprost, 1.10 (0.85-1.42). The mean IOP reductions after 1 month were 1.98 (1.50-2.47), 1.01 (0.55-1.46), 1.08 (0.59-1.57), and 0.46 (-0.41 to 1.33) mm Hg, respectively, and the results were sustained at 3 months. Bimatoprost was associated with the highest risk of developing hyperemia, whereas latanoprost had the lowest risk, with RRs (95% CI) of 4.66 (3.49-6.23) and 2.30 (1.76-3.00), respectively. CONCLUSIONS: Bimatoprost achieved the highest efficacy in terms of IOP reduction, whereas latanoprost had the most favorable tolerability profile. This review serves to guide selection of the optimal PGA agent for individual patient care in clinical practice.

Ten-year prescription trends of asthma medications in the management of childhood wheeze.

Asthma is the most common chronic disorder of childhood. The aim of this study was to assess prescription trends of asthma medications to provide a measure to evaluate treatment practices and compliance with established international practice guidelines. A retrospective study of data obtained from outpatient prescription databases (2001-2010) of the University Children's Medical Institute for children aged 0-18 years was performed. The following drugs were included: short-acting beta-agonists (SABAs), long-acting beta-agonists in combination with inhaled corticosteroids (LABA-ICSs), ICS, and leukotriene receptor antagonists. Statistical analysis of prescription trends was performed with linear regression to determine the trends in prescription of controller medications. From 2001 to 2010, the number of patients who were prescribed SABA increased significantly by 72% (p = 0.016). The increases in ICS patient numbers and ICS/SABA drug unit ratios were significant only in the school-going (>5 years) age group. There was a trend away from the use of nebulized SABA and ICS, although this was statistically insignificant. LABA-ICS patient numbers decreased significantly by 32.4% (p = 0.003), especially in preschoolers (1-5 years). There was a corresponding rise in montelukast patient numbers by 194.6% (p = 0.009) and montelukast/SABA ratio by 345.3% (p = 0.032) in preschoolers (aged 1-5 years). Montelukast patient numbers, but not the montelukast/SABA ratio, increased in school-going children. The move away from LABA-ICS combination especially in younger children and a tendency toward more montelukast usage is a reflection of practice preferences in accordance with current international guidelines in young children.

Impact of pharmacy automation on patient waiting time: an application of computer simulation.

INTRODUCTION: This paper aims to illustrate the use of computer simulation in evaluating the impact of a prototype automated dispensing system on waiting time in an outpatient pharmacy and its potential as a routine tool in pharmacy management. MATERIALS AND METHODS: A discrete event simulation model was developed to investigate the impact of a prototype automated dispensing system on operational efficiency and service standards in an outpatient pharmacy. RESULTS: The simulation results suggest that automating the prescription-filing function using a prototype that picks and packs at 20 seconds per item will not assist the pharmacy in achieving the waiting time target of 30 minutes for all patients. Regardless of the state of automation, to meet the waiting time target, 2 additional pharmacists are needed to overcome the process bottleneck at the point of medication dispense. However, if the automated dispensing is the preferred option, the speed of the system needs to be twice as fast as the current configuration to facilitate the reduction of the 95th percentile patient waiting time to below 30 minutes. The faster processing speed will concomitantly allow the pharmacy to reduce the number of pharmacy technicians from 11 to 8. CONCLUSION: Simulation was found to be a useful and low cost method that allows an otherwise expensive and resource intensive evaluation of new work processes and technology to be completed within a short time.

Novel CYP2C9 genetic variants in Asian subjects and their influence on maintenance warfarin dose.

BACKGROUND: Commonly occurring genetic variants in CYP2C9 are known to reduce catalytic activity and are associated with enhanced patient sensitivity to warfarin. Interethnic differences in warfarin dose requirement have been described in the Asian population, and we postulate that this could be related to genetic variants of CYP2C9 that are unique to ethnic groups. METHODS: We prospectively genotyped 125 patients who were receiving a stable daily warfarin dose to maintain international normalized ratio values between 2 and 3 through comprehensive sequencing of the promoter and coding regions of the CYP2C9 gene. RESULTS: The mean weight-adjusted warfarin maintenance dose was significantly lower for Malay and Chinese subjects than Indian subjects ( P <.001 and.014, respectively). Warfarin dose negatively correlated with age (r = -0.4, P <.001) but not with sex. Multiple variants were detected in the promoter, exonic, intronic, and 3'-untranslated regions of CYP2C9, of which 16 were novel, including 7 nonsynonymous exonic variants ( 208G>C, 374G>A, 485C>A, 895A>G, 1144C>T, 1190A>C, and 1362G>C ). CYP2C9*3, but not CYP2C9*2, was found in Chinese and Malay patients, and carriers of the CYP2C9*3 variant in Chinese ( P <.01) and Indian ( P <.01) patients, but not Malay patients ( P =.77), required less warfarin. The influence of the novel exonic variants on warfarin dose requirement was unclear, because they were rare, but the lower warfarin dose requirement for Chinese and Malay patients existed despite omission of individuals with any coding region variants from analysis. CONCLUSIONS: Interethnic differences in warfarin dosing in Asian subjects may result from other genetic, dietary, or environmental influences; however, these novel variants in the gene warrant further characterization through functional studies.