Estimating the impact of improved management of haemophilia a on clinical outcomes and healthcare utilisation and costs.

OBJECTIVE: Haemophilia A (HA) is associated with high clinical and healthcare burden. We developed an Excel-based model comparing current practice to improved management in severe HA patients currently managed on demand (OD). Outcomes included short- and long-term bleed events. Expected annual bleeds were estimated based on locally-derived OD annualised bleed rate (ABR), adjusted by relative prophylaxis-related ABRs (published literature). The objective of our study was to explore the impact of improving HA prophylaxis in target countries with limited published data (Algeria, Argentina, Chile, India, Malaysia, Mexico, Taiwan and Thailand). Bleed-related healthcare resource use (HCRU) and costs were estimated as a function of bleed type, with inputs obtained from local expert estimates. Clotting factor concentrates (CFC) consumption related to treatment and prophylaxis was estimated based on locally relevant dosing. CFC costs were not included. RESULTS: When 20% of OD patients were switched to prophylaxis, projected reduction in bleeds was estimated between 3% (Taiwan) through 14% (Algeria and India); projected reductions in hospitalisations ranged from 3% (Taiwan) through 15% (India). Projected HCRU-related annual cost savings were estimated at USD 0.45 m (Algeria), 0.77 m (Argentina), 0.28 m (Chile), 0.13 m (India), 0.29 m (Malaysia), 2.79 m (Mexico), 0.15 m (Taiwan) and 0.78 m (Thailand). Net change in annual CFC consumption ranged from a 0.05% reduction (Thailand) to an overall 5.4% increase (Algeria). Our model provides a flexible framework to estimate the clinical and cost offsets of improved prophylaxis. Modest increase in CFC consumption may be an acceptable offset for improvements in health and healthcare capacity in resource constrained economies.

Impact of ixazomib-lenalidomide-dexamethasone therapy on overall survival in multiple myeloma patients: Analysis of the emerging-markets subgroup of the TOURMALINE-MM1 trial.

Ixazomib-lenalidomide-dexamethasone (ixazomib-Rd) showed clinical efficacy over placebo-Rd in patients with relapsed/refractory multiple myeloma (MM) in the TOURMALINE-MM1 trial. Over a median follow-up of ∼85 months, as patients showed disease progression, they received subsequent novel therapies that confounded the overall survival (OS) benefit. Here, we conducted a post hoc analysis in 148 patients from seven countries defined as emerging markets, with limited access to novel therapies for MM during the trial period, to describe the impact of these therapies on OS. Patients were randomised to ixazomib-Rd (n = 71) or placebo-Rd (n = 77). The median progression-free survival (PFS) was 18.7 versus 10.2 months, with ixazomib-Rd versus placebo-Rd (hazard ratio [HR], 0.504; p = 0.008) demonstrating a statistically significant improvement as observed in the primary trial. The median OS improved by 32.6 months with ixazomib-Rd over placebo-Rd (63.5 vs. 30.9 months; HR, 0.794; p = 0.261); however, the statistically significant benefit seen in PFS was not observed for OS. Improvement with ixazomib-Rd over placebo-Rd was observed in overall response (81.7% vs. 64.9%; odds ratio [OR], 2.38; p = 0.019) and complete response (22.5% vs. 3.9%; OR, 7.57; p < 0.001). Patient-reported quality of life and use of subsequent therapies were similar across treatment groups. No new safety concerns were identified. Compared with the main cohort, median OS was 10 months longer with ixazomib-Rd and 21 months shorter with placebo-Rd in this subgroup, indicating a clinically meaningful survival benefit of ixazomib-Rd treatment in this patient population with limited access to subsequent novel therapies.

Predictors of persistent disease activity following anti-VEGF loading dose for nAMD patients in Singapore: the DIALS study.

BACKGROUND: To determine the frequency of persistent disease activity following 3 loading doses of anti- vascular endothelial growth factor (VEGF) agents, and the anatomic and demographic predictors of early persistent disease activity among patients with neovascular age-related macular degeneration (nAMD). METHODS: In a retrospective real-world cohort study, 281 consecutive patients with nAMD were reviewed at baseline and after 3 anti-VEGF injections for pre-defined indicators of disease activity. Optical coherence tomography (OCT) features such as subretinal fluid, intraretinal cysts and intraretinal fluid were assessed by reading-center certified graders. Multiple logistic regression was performed on demographic and anatomic factors. RESULTS: At month 3, 66.1% of patients had persistent disease activity. The best-corrected visual acuity (BCVA) improvement was 0.16 LogMAR for those with no disease activity compared to 0 for patients with persistent activity (p < 0.001). The significant risk factors for persistent activity at 3 months were male gender (odds ratio [OR] 0.54, 95% confidence interval [CI] 0.32-0.93, p = 0.025), intraretinal cysts at baseline (OR 2.95, 95% CI 1.67-5.20, p < 0.001) and subretinal fluid at baseline (OR 3.17, 95% CI 1.62-6.18, p = 0.002). At 3 months, 58% of patients had features of activity on OCT. Patients with intraretinal cysts and intraretinal fluid at baseline had worse BCVA at month 3 compared to patients without these OCT features (0.69 vs. 0.43, p < 0.001, and 0.62 vs. 0.43, p < 0.001, respectively). CONCLUSIONS: In a real-world study, 66.1% of nAMD patients have persistent disease activity after the initial loading dose, with poorer BCVA compared to those without. Baseline OCT features (intraretinal cysts and subretinal fluid) are useful predictors of persistent disease activity at month 3.

Detrimental Effect of Delayed Re-treatment of Active Disease on Outcomes in Neovascular Age-Related Macular Degeneration: The RAMPS Study.

PURPOSE: To assess the impact of delaying anti-vascular endothelial growth factor (VEGF) treatment of active disease at any point during a patient's treatment journey on clinical outcomes in a real-world cohort of patients with neovascular age-related macular degeneration (nAMD). DESIGN: Longitudinal cohort study. PARTICIPANTS: Consecutive treatment-naive nAMD eyes commencing anti-VEGF monotherapy (bevacizumab, ranibizumab, or aflibercept) from January 2014 from a tertiary eye center in Singapore. METHODS: We conducted a real-world study using registry data comparing delayed re-treatment (defined as not receiving treatment at 2 or more monitoring visits when disease was graded as active) versus timely re-treatment (defined as receiving treatment when disease was active). MAIN OUTCOME MEASURES: The primary outcome was the change in visual acuity (VA) in the timely and delayed re-treatment groups at 12 months. RESULTS: Data from 286 eyes were included and categorized into the timely (188 [66%]) or the delayed (98 ([34%]) group. The mean numbers of anti-VEGF injections over 12 months were similar: 5.6 (standard deviation [SD], 2.9) versus 4.9 (SD, 3.2; P = 0.11) for the timely and delayed groups, respectively. Timely treated patients showed larger gains in VA (6.4 letters [SD, 8.1 letters] vs. 1.2 letters [SD, 5.3 letters; P = 0.04), a higher proportion with VA of 6/12 or better (30% vs. 8%; P = 0.01), and greater reduction in OCT-measured central subfield thickness (135 µm [SD, 154 µm] vs. 87.8 µm [SD, 129 µm]; P = 0.04) at 12 months. A longer delay between detection of active disease and re-treatment was associated with poorer vision outcomes (0.02-letter decrease/day; P = 0.03; R2 = 0.29). CONCLUSIONS: Although it has been established that adequate numbers of injections are required for favorable outcomes, timely re-treatment of active disease also is important. This should be emphasized to patients to ensure optimal outcomes in real-world clinical settings.

Cost-effectiveness of Intravitreal Ranibizumab With Verteporfin Photodynamic Therapy Compared With Ranibizumab Monotherapy for Patients With Polypoidal Choroidal Vasculopathy.

Importance: The EVEREST II trial showed that for patients with polypoidal choroidal vasculopathy (PCV), intravitreal ranibizumab in combination with verteporfin photodynamic therapy improves visual acuity relative to ranibizumab monotherapy. However, whether combination therapy is incrementally cost-effective relative to monotherapy during a lifetime is unclear. Objective: To assess the incremental cost-effectiveness of combination therapy compared with ranibizumab monotherapy in patients with PCV. Design, Setting, and Participants: This model-based, economic evaluation used 2018 unit cost data from a tertiary eye hospital in Singapore, first- and second-year outcomes and resource use data from a multicenter trial across various Asian countries (EVEREST II) to model a hypothetical cohort of patients with symptomatic PCV. Scenario analyses and deterministic and probabilistic sensitivity analyses were performed to examine uncertainty. Data were collected from October 2018 through April 2019 and analyzed from March through October 2019. Interventions: This model used data from the EVEREST II trial, in which all participants were given 0.5 mg of intravitreal ranibizumab once every 4 weeks for the first 3 months. Subsequent administration occurred as needed. For participants receiving combination therapy, standard fluence (50 J/cm3) photodynamic therapy with 6-mg/m2 verteporfin was administered once during the first 3 months and thereafter as needed. Main Outcomes and Measures: Incremental cost per quality-adjusted life-year (QALY) gained for combination therapy relative to monotherapy for patients with PCV. Results: In this model based on a cohort of 1000 patients aged 68 years, a patient with PCV incurred a total cost in Singapore dollars (SGD) of 92 327 (US $67 399) with combination therapy and SGD 92 371 (US $67 431) with monotherapy during a lifetime horizon, generating a modest cost savings of SGD 44 (US $32) per patient undergoing combination therapy. Lifetime QALYs were estimated to be 7.87 for combination therapy and 7.85 for monotherapy, for an incremental gain of 0.02 QALYs. Combination therapy remained cost-saving or cost-effective in all lifetime scenarios modeled, but during shorter time horizons and at lower monotherapy costs, it may not be cost-effective. Conclusions and Relevance: This study found combination therapy to be a dominant (more effective and less costly) strategy, being similar in costs and slightly more effective than ranibizumab monotherapy during a lifetime horizon. However, decreasing the time horizon to less than 10 years and/or reductions in the cost of monotherapy may result in combination therapy no longer being cost-effective.

Virtual Patient Simulations in Health Professions Education: Systematic Review and Meta-Analysis by the Digital Health Education Collaboration.

BACKGROUND: Virtual patients are interactive digital simulations of clinical scenarios for the purpose of health professions education. There is no current collated evidence on the effectiveness of this form of education. OBJECTIVE: The goal of this study was to evaluate the effectiveness of virtual patients compared with traditional education, blended with traditional education, compared with other types of digital education, and design variants of virtual patients in health professions education. The outcomes of interest were knowledge, skills, attitudes, and satisfaction. METHODS: We performed a systematic review on the effectiveness of virtual patient simulations in pre- and postregistration health professions education following Cochrane methodology. We searched 7 databases from the year 1990 up to September 2018. No language restrictions were applied. We included randomized controlled trials and cluster randomized trials. We independently selected studies, extracted data, and assessed risk of bias and then compared the information in pairs. We contacted study authors for additional information if necessary. All pooled analyses were based on random-effects models. RESULTS: A total of 51 trials involving 4696 participants met our inclusion criteria. Furthermore, 25 studies compared virtual patients with traditional education, 11 studies investigated virtual patients as blended learning, 5 studies compared virtual patients with different forms of digital education, and 10 studies compared different design variants. The pooled analysis of studies comparing the effect of virtual patients to traditional education showed similar results for knowledge (standardized mean difference [SMD]=0.11, 95% CI -0.17 to 0.39, I2=74%, n=927) and favored virtual patients for skills (SMD=0.90, 95% CI 0.49 to 1.32, I2=88%, n=897). Studies measuring attitudes and satisfaction predominantly used surveys with item-by-item comparison. Trials comparing virtual patients with different forms of digital education and design variants were not numerous enough to give clear recommendations. Several methodological limitations in the included studies and heterogeneity contributed to a generally low quality of evidence. CONCLUSIONS: Low to modest and mixed evidence suggests that when compared with traditional education, virtual patients can more effectively improve skills, and at least as effectively improve knowledge. The skills that improved were clinical reasoning, procedural skills, and a mix of procedural and team skills. We found evidence of effectiveness in both high-income and low- and middle-income countries, demonstrating the global applicability of virtual patients. Further research should explore the utility of different design variants of virtual patients.

Is there scope for expanding the optometrist's scope of practice in Singapore? - A survey of optometrists, opticians in Singapore.

PURPOSE: In Singapore, optometrists' roles are limited compared to their counterparts elsewhere. The purpose of the survey is to investigate optometrists' current roles, views on extended roles, self-reported primary eye care knowledge, needs for continuing professional education (CPE) and views on suitable modes for CPE. METHODS: Members of the Optometrist and Optician Board (OOB) were invited via email to take part in an anonymous online survey. The survey questions covered the following areas: current scope of practice, self-rated primary eye care knowledge, confidence in screening, co-managing minor eye conditions, CPE and referral behavior. RESULTS: A total of 230 optometrists completed the survey (response rate 30%). Their current roles were limited to diagnostic refraction (92%), colour vision assessment (65%), contact lens fitting and dispensing (62%) amongst others. The average self-rated score for primary eye care knowledge was 8.2 ± 1.4; score range 1-10 (1-Very poor, 10-Excellent). Self-rated confidence scores for screening for cataract, diabetic retinopathy, chronic glaucoma and age-related macular degeneration were 2.7 ± 1.5, 3.7 ± 1.9, 4.0 ± 1.9 and 3.8 ± 1.8, respectively. 71% of the optometrists felt that they should undertake regular CPE to improve their primary eye care knowledge. Blended learning (eLearning and traditional face-to-face lectures) (46.1%) was the most preferred mode for CPE delivery. CONCLUSION: Optometrists in Singapore represent a skilled underutilized primary eye care provider. Though their self-reported primary eye care knowledge is high, their confidence in screening and co-managing chronic eye conditions is low. Enabling them for extended primary eye care role would require further training. SIGNIFICANCE: Singapore ageing population has led to greater eye care demands. Task-shifting from ophthalmologists to optometrists has been proposed in the literature to handle this growing care demands. At this juncture, this study provides evidence based answers to issues revolving around optometrists' readiness for a role expansion in Singapore.

Online Digital Education for Postregistration Training of Medical Doctors: Systematic Review by the Digital Health Education Collaboration.

BACKGROUND: Globally, online and local area network-based (LAN) digital education (ODE) has grown in popularity. Blended learning is used by ODE along with traditional learning. Studies have shown the increasing potential of these technologies in training medical doctors; however, the evidence for its effectiveness and cost-effectiveness is unclear. OBJECTIVE: This systematic review evaluated the effectiveness of online and LAN-based ODE in improving practicing medical doctors' knowledge, skills, attitude, satisfaction (primary outcomes), practice or behavior change, patient outcomes, and cost-effectiveness (secondary outcomes). METHODS: We searched seven electronic databased for randomized controlled trials, cluster-randomized trials, and quasi-randomized trials from January 1990 to March 2017. Two review authors independently extracted data and assessed the risk of bias. We have presented the findings narratively. We mainly compared ODE with self-directed/face-to-face learning and blended learning with self-directed/face-to-face learning. RESULTS: A total of 93 studies (N=16,895) were included, of which 76 compared ODE (including blended) and self-directed/face-to-face learning. Overall, the effect of ODE (including blended) on postintervention knowledge, skills, attitude, satisfaction, practice or behavior change, and patient outcomes was inconsistent and ranged mostly from no difference between the groups to higher postintervention score in the intervention group (small to large effect size, very low to low quality evidence). Twenty-one studies reported higher knowledge scores (small to large effect size and very low quality) for the intervention, while 20 studies reported no difference in knowledge between the groups. Seven studies reported higher skill score in the intervention (large effect size and low quality), while 13 studies reported no difference in the skill scores between the groups. One study reported a higher attitude score for the intervention (very low quality), while four studies reported no difference in the attitude score between the groups. Four studies reported higher postintervention physician satisfaction with the intervention (large effect size and low quality), while six studies reported no difference in satisfaction between the groups. Eight studies reported higher postintervention practice or behavior change for the ODE group (small to moderate effect size and low quality), while five studies reported no difference in practice or behavior change between the groups. One study reported higher improvement in patient outcome, while three others reported no difference in patient outcome between the groups. None of the included studies reported any unintended/adverse effects or cost-effectiveness of the interventions. CONCLUSIONS: Empiric evidence showed that ODE and blended learning may be equivalent to self-directed/face-to-face learning for training practicing physicians. Few other studies demonstrated that ODE and blended learning may significantly improve learning outcomes compared to self-directed/face-to-face learning. The quality of the evidence in these studies was found to be very low for knowledge. Further high-quality randomized controlled trials are required to confirm these findings.

Virtual Reality for Health Professions Education: Systematic Review and Meta-Analysis by the Digital Health Education Collaboration.

BACKGROUND: Virtual reality (VR) is a technology that allows the user to explore and manipulate computer-generated real or artificial three-dimensional multimedia sensory environments in real time to gain practical knowledge that can be used in clinical practice. OBJECTIVE: The aim of this systematic review was to evaluate the effectiveness of VR for educating health professionals and improving their knowledge, cognitive skills, attitudes, and satisfaction. METHODS: We performed a systematic review of the effectiveness of VR in pre- and postregistration health professions education following the gold standard Cochrane methodology. We searched 7 databases from the year 1990 to August 2017. No language restrictions were applied. We included randomized controlled trials and cluster-randomized trials. We independently selected studies, extracted data, and assessed risk of bias, and then, we compared the information in pairs. We contacted authors of the studies for additional information if necessary. All pooled analyses were based on random-effects models. We used the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach to rate the quality of the body of evidence. RESULTS: A total of 31 studies (2407 participants) were included. Meta-analysis of 8 studies found that VR slightly improves postintervention knowledge scores when compared with traditional learning (standardized mean difference [SMD]=0.44; 95% CI 0.18-0.69; I2=49%; 603 participants; moderate certainty evidence) or other types of digital education such as online or offline digital education (SMD=0.43; 95% CI 0.07-0.79; I2=78%; 608 participants [8 studies]; low certainty evidence). Another meta-analysis of 4 studies found that VR improves health professionals' cognitive skills when compared with traditional learning (SMD=1.12; 95% CI 0.81-1.43; I2=0%; 235 participants; large effect size; moderate certainty evidence). Two studies compared the effect of VR with other forms of digital education on skills, favoring the VR group (SMD=0.5; 95% CI 0.32-0.69; I2=0%; 467 participants; moderate effect size; low certainty evidence). The findings for attitudes and satisfaction were mixed and inconclusive. None of the studies reported any patient-related outcomes, behavior change, as well as unintended or adverse effects of VR. Overall, the certainty of evidence according to the GRADE criteria ranged from low to moderate. We downgraded our certainty of evidence primarily because of the risk of bias and/or inconsistency. CONCLUSIONS: We found evidence suggesting that VR improves postintervention knowledge and skills outcomes of health professionals when compared with traditional education or other types of digital education such as online or offline digital education. The findings on other outcomes are limited. Future research should evaluate the effectiveness of immersive and interactive forms of VR and evaluate other outcomes such as attitude, satisfaction, cost-effectiveness, and clinical practice or behavior change.

Effect of multimorbidity on survival of patients diagnosed with heart failure: a retrospective cohort study in Singapore.

OBJECTIVE: Multimorbidity in patients with heart failure (HF) results in poor prognosis and is an increasing public health concern. We aim to examine the effect of multimorbidity focusing on type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) on all-cause and cardiovascular disease (CVD)-specific mortality among patients diagnosed with HF in Singapore. DESIGN: Retrospective cohort study. SETTING: Primary and tertiary care in three (out of six) Regional Health Systems in Singapore. PARTICIPANTS: Patients diagnosed with HF between 2003 and 2016 from three restructured hospitals and nine primary care polyclinics were included in this retrospective cohort study. PRIMARY OUTCOMES: All-cause mortality and CVD-specific mortality. RESULTS: A total of 34 460 patients diagnosed with HF from 2003 to 2016 were included in this study and were followed up until 31 December 2016. The median follow-up time was 2.1 years. Comorbidities prior to HF diagnosis were considered. Patients were categorised as (1) HF only, (2) T2DM+HF, (3) CKD+HF and (4) T2DM+CKD+HF. Cox regression model was used to determine the effect of multimorbidity on (1) all-cause mortality and (2) CVD-specific mortality. Adjusting for demographics, other comorbidities, baseline treatment and duration of T2DM prior to HF diagnosis, 'T2DM+CKD+HF' patients had a 56% higher risk of all-cause mortality (HR: 1.56, 95% CI 1.48 to 1.63) and a 44% higher risk of CVD-specific mortality (HR: 1.44, 95% CI 1.32 to 1.56) compared with patients diagnosed with HF only. CONCLUSION: All-cause and CVD-specific mortality risks increased with increasing multimorbidity. This study highlights the need for a new model of care that focuses on holistic patient management rather than disease management alone to improve survival among patients with HF with multimorbidity.

Evaluation of an integrated primary care-led dementia shared care program in Singapore: An effectiveness and cost-effectiveness study.

AIM: With an aging Singapore population, there is an increasing demand for dementia care. The present study aimed to evaluate the effectiveness and cost-effectiveness of the Primary Care Dementia Clinic (PCDC) in comparison with the Memory Clinic (MC; hospital-based) and other polyclinics. METHODS: A quasi-experimental design was implemented. Effectiveness of PCDC was assessed through caregiver satisfaction, quality of life (caregiver-rated) and adverse events rates. Quality-of-Life measures using the EuroQol 5 Dimension Questionnaire (EQ-5D) at baseline, 6 months and 12 months was assessed. Costs were calculated from a societal perspective. The incremental cost-effectiveness of the PCDC was compared with MC and other polyclinics. RESULTS: The present study showed that quality of life and the rate of adverse events at 12 months were similar between the three groups. Caregiver satisfaction at 12 months was higher in the PCDC group when compared with other polyclinics. There were no observed differences in societal cost between the three groups. At 6-month follow up, direct medical costs for PCDC were significantly lower that of other polyclinics. At 12-month follow up, PCDC patients had higher Quality Adjusted Life Years (QALYs) compared with the MC group. CONCLUSION: PCDC provided effective care, similar to care at MC and better than care at other polyclinics. Caregiver satisfaction was higher for the PCDC group, and PCDC patients had lower direct medical costs at 6-month follow up. Given these findings, adopting a PCDC model in other polyclinics in Singapore can be beneficial for optimal right siting of patients. Geriatr Gerontol Int 2018; 18: 479-486.

Effectiveness of Diabetes Foot Screening in Primary Care in Preventing Lower Extremity Amputations.

INTRODUCTION: The risk of lower extremity amputations (LEAs) in diabetics is 20 times higher than in non-diabetics. Clinical practice guidelines recommend that all diabetics should receive an annual foot examination to identify high-risk foot conditions. Despite this recommendation, there is little evidence in the literature to show its effectiveness in preventing LEA. This study aims to evaluate the effectiveness of diabetes foot screening in primary care in preventing LEA and to identify LEA risk factors. MATERIALS AND METHODS: This is a retrospective cohort study of diabetic patients who visited the National Healthcare Group Polyclinics for the first time from 1 January 2008 to 31 December 2012. The intervention of interest was foot screening performed at least once during 2 years of follow-up, and the outcome of interest was LEA (major and/or minor) performed during 2 years of follow-up. Patients who did foot screening (n=8150) were compared to a propensity score matched control group (n=8150) who did not do foot screening. Logistics regression was done to identify factors associated with LEA. RESULTS: Among those who underwent foot screening, there were 2 (0.02%) major amputations and 15 (0.18%) minor amputations compared with 42 (0.52%) and 52 (0.64%) among those who did not (P<0.001). CONCLUSION: Lack of diabetes foot screening, lower socioeconomic status, hip fracture, Malay ethnicity, chronic kidney disease, poorer glycaemic control, longer diabetes duration and male gender have been found to be associated with a higher risk of LEA.

Singapore's regional health systems-a data-driven perspective on frequent admitters and cross utilization of healthcare services in three systems.

INTRODUCTION: With population health management being a priority in the Singapore, this paper aims to provide a data-driven perspective of the population health management initiatives to aid program planning and serves as a baseline for evaluation of future implemented programs. METHODS: A database with information on patient demographics, health services utilization, cost, diagnoses and chronic disease information from 2008 to 2013 for three regional health systems in Singapore was used for analysis. Patients with three or more inpatient admissions were considered as "Frequent Admitters." Health service utilization was quantified, and cross utilization of services was studied. One-year readmission rate for inpatients was studied, and a predictive model for readmission or death was developed. RESULTS: There were a total of 2.8 M patients in the database. Frequent admitters accounted for 0.9% of all patients with an average cost per patient of S$29 547. Of these, 89% had chronic diseases. Cross utilization of health services showed that 8.2% of the patients utilized services from more than one hospital with 19.6% utilizing hospital and polyclinic services in 2013. The highest risk of readmission or death was for those patients who had five or more inpatient episodes in each of the preceding 2 years. CONCLUSION: By understanding the profile of the patients and their utilization patterns in the three regional health systems, our study will help clinicians and decision makers design appropriate integrated care programs for patients with the aim of covering the healthcare needs for the enitre population across the healthcare spectrum in Singapore. Copyright © 2015 John Wiley & Sons, Ltd.

Burden of Wet Age-Related Macular Degeneration and Its Economic Implications in Singapore in the Year 2030.

PURPOSE: To estimate the prevalence of wet age-related macular degeneration (AMD) in Singapore in the year 2030. This projection will help in planning appropriate care provision and build health services capacity to cater to the increasing healthcare demand in 2030. METHODS: The number of AMD patients aged 40-79 years from all Singaporeans was estimated using prevalence rates from a local study and using the United Nations population projections for Singapore to 2030. Age-specific mortality was accounted for. Additionally, two main scenarios were presented: (1) Projected number of wet AMD cases if patients were not taking preventive antioxidant vitamins; (2) projected number of wet AMD cases if patients were taking preventive antioxidant vitamins. Based on these scenarios, the economic burden was calculated. The number of quality-adjusted life years (QALYs) gained as a result of improvement in visual acuity (VA) due to anti-vascular endothelial growth factor (VEGF) treatment was also calculated. RESULTS: An estimated growth of 42% in the number of wet AMD cases is expected by 2030. The estimated economic burden of wet AMD in 2030 for scenarios 1 and 2 is Singapore $203.1 million and $162.9 million, respectively. The QALYs gained as a result of improved VA from wet AMD treatment ranged from 10,114.4 to 14,058.8 over a 5-year period for the 2030 cohort. CONCLUSION: The burden of wet AMD is set to increase over the next 15 years. Appropriate measures to build healthcare capacity and plan for this expected surge in patients should be a priority in Singapore.

Annual all-cause mortality rate for patients with diabetic kidney disease in Singapore.

BACKGROUND: The prognosis of diabetic kidney disease is poor because epidemiological data have shown that all-cause mortality increases with declining renal function. This study aims to estimate the annual mortality rate of diabetic kidney disease stratified by chronic kidney disease (CKD) stages and to identify the predictors of mortality. METHODS: Patients with Stage 3-5 CKD (estimated glomerular filtration rate [eGFR] less than 60 mL/min per 1.73 m2) with diabetic kidney disease from the National Healthcare Group CKD Registry from 1 January 2007 to 31 December 2007 were included in this study. The patients were followed up till 30 November 2013. Cox's proportional hazards regression modelling was used to assess the factors associated with all-cause mortality. RESULTS: Over a median follow up period of 6.0 years, 985 out of 3008 patients (32.8%) died. Of those who died, 363 (36.9%) died from cardiovascular causes. The annual mortality rate was 64.1 per 1000 individuals (95% confidence interval [CI] 60.2-68.3) and the mortality rate increased with severity of CKD [Stage 3A (37.0), Stage 3B (57.5), Stage 4 (98.3) and Stage 5 (198.5)]. Predictors of mortality were age, male gender, CKD stages, albuminuria, comorbid conditions such as peripheral vascular disease, neuropathy, retinopathy and the use of antiplatelet agents. CONCLUSION: Our study estimated the annual all-cause mortality rate for Singaporean patients with diabetic kidney disease by CKD stages and identified predictors of all-cause mortality. This study has affirmed the poor prognosis of these patients and an urgency to intervene early so as to retard the progression to later stages of CKD.

Cost-effectiveness of anti-oxidant vitamins plus zinc treatment to prevent the progression of intermediate age-related macular degeneration. A Singapore perspective.

PURPOSE: To determine if providing high dose anti-oxidant vitamins and zinc treatment age-related eye disease study (AREDS formulation) to patients with intermediate age-related macular degeneration (AMD) aged 40-79 years from Singapore is cost-effective in preventing progression to wet AMD. METHODS: A hypothetical cohort of category 3 and 4 AMD patients from Singapore was followed for 5 calendar years to determine the number of patients who would progress to wet AMD given the following treatment scenarios: (a) AREDS formulation or placebo followed by ranibizumab (as needed) for wet AMD. (b) AREDS formulation or placebo followed by bevacizumab (monthly) for wet AMD. (c) AREDS formulation or placebo followed by aflibercept (VIEW I and II trial treatment regimen). Costs were estimated for the above scenarios from the providers' perspective, and cost-effectiveness was measured by cost per disability-adjusted life year (DALY) averted with a disability weight of 0.22 for wet AMD. The costs were discounted at an annual rate of 3%. RESULTS: Over 5400 patients could be prevented from progressing to wet AMD cumulatively if AREDS formulation were prescribed. AREDS formulation followed by ranibizumab was cost-effective compared to placebo-ranibizumab or placebo-aflibercept combinations (cost per DALY averted: SGD$23,662.3 and SGD$21,138.8, respectively). However, bevacizumab (monthly injections) alone was more cost-effective compared to AREDS formulation followed by bevacizumab. CONCLUSION: Prophylactic treatment with AREDS formulation for intermediate AMD patients followed by ranibizumab or for patients who progressed to wet AMD was found to be cost-effective. These findings have implications for intermediate AMD screening, treatment and healthcare planning in Singapore.

Longer examination time improves detection of gastric cancer during diagnostic upper gastrointestinal endoscopy.

BACKGROUND & AIMS: It is not clear how the duration of upper endoscopy affects the detection of cancer or premalignant lesions that increase the risk for gastric cancer. We investigated whether the length of time spent performing esophagogastroduodenoscopy (EGD) affects the detection of important pathologic features of the stomach. METHODS: We collected data from 837 symptomatic patients, during a 3-month period in 2010, who underwent a first diagnostic EGD at a tertiary university hospital in Singapore. Endoscopists were classified as fast or slow based on the mean amount of time it took them to perform a normal EGD examination. We used logistic regression to compare between groups the numbers of intestinal metaplasias, gastric atrophies, dysplasias, and cancers detected, using histologic analysis of biopsy samples collected during endoscopy as the standard. RESULTS: Of 224 normal endoscopies, the mean duration was 6.6 minutes (range, 2-32 min). When we used 7 minutes as the cut-off time, 8 endoscopists were considered to have short mean examination times (mean duration, 5.5 ± 2.1 min; referred to as fast endoscopists), and 8 endoscopists were considered to have long mean examination times (mean duration, 8.6 ± 4.2 min; referred to as slow endoscopists). Eleven cancers and 81 lesions considered to pose risks for cancer were detected in 86 patients; 1.3% were determined to be cancer, 1.0% were determined to be dysplasia, and 8.7% were determined to be intestinal metaplasia and/or gastric atrophy. Slow endoscopists were twice as likely to detect high-risk lesions as fast endoscopists (odds ratio, 2.50; 95% confidence interval, 1.52-4.12), regardless of whether they were endoscopy staff or trainees. The slow endoscopists also detected 3-fold more neoplastic lesions (cancer or dysplasia; odds ratio, 3.42; 95% confidence interval, 1.25-10.38). CONCLUSIONS: Endoscopists with mean EGD examination times longer than 7 minutes identified a greater number of high-risk gastric lesions than faster endoscopists. Examination time may be a useful indicator of quality assessment for upper endoscopy. Studies are required to test these findings in different populations.

Does the axillary lymph node ratio have any added prognostic value over pN staging for South East Asian breast cancer patients?

INTRODUCTION: Lymph node ratio (LNR, i.e. the ratio of the number of positive nodes to the total number of nodes excised) is reported to be superior to the absolute number of nodes involved (pN stage) in classifying patients at high versus low risk of death following breast cancer. The added prognostic value of LNR over pN in addition to other prognostic factors has never been assessed. METHODS: All patients diagnosed with lymph node positive, non-metastatic invasive breast cancer at the National University Hospital (Singapore) and University of Malaya Medical Center (Kuala Lumpur) between 1990-2007 were included (n = 1589). Overall survival of the patients was estimated by the Kaplan Meier method for LNR [categorized as low (>0 and <0.2), intermediate (0.2-0.65) and high (>0.65-1)] and pN staging [pN1, pN2 and pN3]. Adjusted overall relative mortality risks associated with LNR and pN were calculated by Cox regression. The added prognostic value of LNR over pN was evaluated by comparing the discriminating capacity (as indicated by the c statistic) of two multivariate models, one including pN and one including LNR. RESULTS: LNR was superior to pN in categorizing mortality risks for women ≥60 years, those with ER negative or grade 3 tumors. In combination with other factors (i.e. age, treatment, grade, tumor size and receptor status), substituting pN by LNR did not result in better discrimination of women at high versus low risk of death, neither for the entire cohort (c statistic 0.72 [0.70-0.75] and 0.73 [0.71-0.76] respectively for pN versus LNR), nor for the subgroups mentioned above. CONCLUSION: In combination with other prognosticators, substitution of pN by LNR did not provide any added prognostic value for South East Asian breast cancer patients.

Breast cancer in South East Asia: comparison of presentation and outcome between a middle income and a high income country.

BACKGROUND: There are large differences in socio-economic growth within the region of South East Asia, leading to sharp contrasts in health-systems development between countries. This study compares breast cancer presentation and outcome between patients from a high income country (Singapore) and a middle income country (Malaysia) in South East Asia. METHODS: Within the Singapore Malaysia Breast Cancer Registry we identified all consecutive patients diagnosed with breast cancer between 1993 and 2007 at the National University Hospital in Singapore (high income country, n=2,141) and the University of Malaya Medical Center in Kuala Lumpur, Malaysia (middle income country, n=3,320). We compared demographics, tumor characteristics, treatment patterns, and survival between patients from both countries. RESULTS: In Malaysia, patients were less often diagnosed with in situ breast cancer (adjusted odds ratio [ORadj] 0.2; 95% confidence interval [95% CI] 0.1-0.3), more likely to be diagnosed with late stage (III and IV) disease (ORadj for stage III 1.6; 95% CI 1.3-2.0; ORadj for stage IV 1.2; 95% CI 1.1-1.4) as compared to patients from Singapore. Univariate analysis showed that Malaysian patients were at a 72% increased risk of death as compared to Singaporeans. After adjusting for other prognostic factors, the risk decreased by only 5% (ORadj 1.67, 95% CI 1.44-1.92). CONCLUSIONS: Differences in way of presentation (except stage and tumor size) and treatment of breast cancer patients from the two countries are small. The overall survival of breast cancer patients from Malaysia is much lower than that of Singaporean patients.