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ABSTRACT: The main objective was to explore the relationship between socioeconomic status and the spatial distribution of ambulance calls, as modeled in the island nation of Singapore, at the Development Guide Plan (DGP) level (equivalent to census tracts in the United States).
Ambulance call data came from a nationwide registry from January to May 2006. We used a conditional autoregressive (CAR) model to create smoothed maps of ambulance calls at the DGP level, as well as spatial regression models to evaluate the relationship between the risk of calls with regional measures of socioeconomic status, such as household type and both personal and household income.
There was geographical correlation in the ambulance calls, as well as a socioeconomic gradient in the relationship with ambulance calls of medical-related (but not trauma-related) reasons. For instance, the relative risk (RR) of medical ambulance calls decreased by a factor of 0.66 (95% credible interval [CrI] = 0.56 to 0.79) for every 10% increase in the proportion of those with monthly household income S$5000 and above. The top three DGPs with the highest risk of medical-related ambulance calls were Changi (RR = 29, 95% CrI = 24 to 35), downtown core (RR = 8, 95% CrI = 6 to 9), and Orchard (RR = 5, 95% CrI = 4 to 6).
This study demonstrates the utility of geospatial analysis to relate population socioeconomic factors with ambulance call volumes. This can serve as a model for analysis of other public health systems.
Academic Emergency Medicine 02/2012; 19(2):180-8. · 1.86 Impact Factor
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ABSTRACT: Diabetes mellitus (DM) has been declared as a global public health threat to society. However, the burden of the disease in elderly Asian patients has not been described. The aim of the study is to assess the disease burden of DM and its associated adverse outcomes in elderly patients from an Asian hospital using the hospital inpatient database.
Retrospective study of hospital discharge database from 2004 to 2008 to identify patients aged 65 years and above with DM and its associated 'adverse outcomes' using International Statistical Classification of Diseases and Related Health Problems, 9th Revision, Australian Modification (ICD-9-AM) codes.
Of 89,875 hospitalized patients aged 65 years and above over the 5 years, 31,124 (34.6%) patients had DM, and the percentage of DM cases increased steadily from 34.3% to 35.6%. Prevalence of DM-associated adverse outcomes was higher in DM patients than in non-DM patients (53.8% vs. 31.5%, p<0.001). For trends over time, the adverse outcomes decreased in both DM patients (58.1% to 53.6%) and non-DM patients (34.3% to 31.4%, all p<0.001). All disease-specific adverse outcomes except renal disease decreased over time both in DM and non-DM patients (all p<0.05). There were increased trends over time for renal disease in both DM patients (16.1% to 23.2%, p<0.001) and non-DM patients (6.7% to 10.4%, p<0.001).
The burden of DM in this group of elderly patients is high. Elderly patients with DM experienced much higher rates of the adverse outcomes.
European Journal of Internal Medicine 01/2012; 23(1):e1-4. · 2.00 Impact Factor
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ABSTRACT: Sample sizes for studies that aim to estimate differences in proportions are often calculated using a confidence interval approach. In particular, the methods advocated by Day ( 1988 ) and Bristol ( 1989 ), based on asymptotic normal approximations, are commonly used. We compare these to the Wilson score approach discussed by Newcombe ( 1998 ) and show, except for extreme values, that the Day method gives results close to those of Wilson score method, while that of Bristol is consistently higher. We argue that the asymptotic normal approximation approach of Day serves as a better guide for quick calculations of sample sizes.
Journal of Biopharmaceutical Statistics 01/2012; 22(1):133-40. · 1.34 Impact Factor
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ABSTRACT: Dengue fever (DF) is a serious public health problem in many parts of the world, and, in the absence of a vaccine, disease surveillance and mosquito vector eradication are important in controlling the spread of the disease. DF is primarily transmitted by the female Aedes aegypti mosquito. We compared two statistical models that can be used in the surveillance and forecast of notifiable infectious diseases, namely, the Autoregressive Integrated Moving Average (ARIMA) model and the Knorr-Held two-component (K-H) model. The Mean Absolute Percentage Error (MAPE) was used to compare models. We developed the models using used data on DF notifications in Singapore from January 2001 till December 2006 and then validated the models with data from January 2007 till June 2008. The K-H model resulted in a slightly lower MAPE value of 17.21 as compared to the ARIMA model. We conclude that the models' performances are similar, but we found that the K-H model was relatively more difficult to fit in terms of the specification of the prior parameters and the relatively longer time taken to run the models.
Computational and Mathematical Methods in Medicine 01/2012; 2012:758674. · 0.68 Impact Factor
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ABSTRACT: To investigate the relationship between body mass and health-related quality of life (HRQOL) among Singaporean adolescents. Variation in this relationship by age, gender and ethnicity, and association of HRQOL with change in body mass over time and with demographic, socioeconomic and health variables were also assessed.
HRQOL was assessed for Singaporean adolescents aged 11-18 from their own (N=1,249) and their parent’s (N=948) perspective using PedsQLTM 4.0 generic core scales. Body mass, measured as body mass index z-score based on the WHO Reference 2007, was categorized as thin, healthy weight, overweight and obese. Multiple linear regression models assessed the relationship between current body mass and HRQOL, adjusting for demographic, socioeconomic and health variables. Differences between adolescent and parent-proxy reported HRQOL were also investigated.
Obese adolescents (and their parents) reported significantly lower HRQOL, overall and in most domains, compared to healthy weight adolescents. Parents tended to report lower HRQOL for their adolescents than the adolescents did themselves; however, this difference was much larger and statistically significant for obese adolescents.
Obesity is associated with reduced HRQOL among adolescents. The effect in these Singaporean adolescents is similar to that in populations with higher rates of obesity. Awareness of this relationship can make it easier for health professionals, teachers, parents and peers to be supportive of obese adolescents.
Quality of Life Research 03/2010; 19(2):167-76. · 2.30 Impact Factor
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ABSTRACT: The number of novel and molecularly targeted agents in the last decade that need screening for preliminary efficacy in Phase II trials has increased. Many of these agents have a cytostatic mode of action that is difficult to assess using traditional Phase II designs. These new agents require detailed evaluation to optimize their dosing, to evaluate their effects on their target and to define early markers that predict for a definitive benefit. This review focuses on the options for Phase II trial designs. The different end points, single versus multiarm and randomized designs, the use of biomarkers and Bayesian approaches are also reviewed. The final design chosen will depend on the characteristics and circumstances of each individual study.
Expert Review of Anti-infective Therapy 03/2010; 10(3):427-38. · 2.65 Impact Factor
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ABSTRACT: A Royal Statistical Society Working Party recently recommended that "Greater use should be made of numerical, as opposed to verbal, descriptions of risk" in first-in-man clinical trials. This echoed the view of many clinicians and psychologists about risk communication. As the clinical trial industry expands rapidly across the globe, it is important to understand risk communication in Asian countries.
We conducted a cognitive experiment about participation in a hypothetical clinical trial of a pain relief medication and a survey in cancer and arthritis patients in Singapore. In part 1 of the experiment, the patients received information about the risk of side effects in one of three formats (frequency, percentage and verbal descriptor) and in one of two sequences (from least to most severe and from most to least severe), and were asked about their willingness to participate. In part 2, the patients received information about the risk in all three formats, in the same sequence, and were again asked about their willingness to participate. A survey of preference for risk presentation methods and usage of verbal descriptors immediately followed.
Willingness to participate and the likelihood of changing one's decision were not affected by the risk presentation methods. Most patients indicated a preference for the frequency format, but patients with primary school or no formal education were indifferent. While the patients used the verbal descriptors "very common", "common" and "very rare" in ways similar to the European Commission's Guidelines, their usage of the descriptors "uncommon" and "rare" was substantially different from the EU's.
In this sample of Asian cancer and arthritis patients, risk presentation format had no impact on willingness to participate in a clinical trial. However, there is a clear preference for the frequency format. The lay use of verbal descriptors was substantially different from the EU's.
BMC Medical Informatics and Decision Making 01/2010; 10:55. · 1.48 Impact Factor
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ABSTRACT: To describe and compare ocular component growth curves among different refractive error groups in Singaporean children.
Data collected yearly in 1775 Asian children aged 6 to 10 years with at least three visits were analyzed. Cycloplegic refractive error and biometry variables were measured by autorefractor and A-scan ultrasound machine. Growth curves were compared between five groups: persistent hyperopia of spherical equivalent (SE) > +1.00 D, emmetropizing hyperopia of SE > +1.00 D on the first visit and between -0.50 D and +1.00 D subsequently, persistent emmetropia of SE between -0.50 D and +1.00 D, incident myopia of SE <or= -0.50 D at subsequent visits, and persistent myopia of SE <or= -0.50 D.
The axial length and vitreous chamber elongated faster in the children younger than 10 years, but elongation slowed with age. Growth patterns of axial length and vitreous chamber in the children with newly developed or persistent myopia (P < 0.01) showed faster elongation than in the emmetropic children. The anterior chamber deepened until approximately 9 or 10 years of age but became shallower as the myopic and emmetropic children grew older. Conversely, the lens thinned at younger ages and thickened at older ages for all except the persistently hyperopic children.
In young Asian children, the axial length and vitreous chamber depth increased, but the elongation slowed with age. There was a U-shaped growth curve for lens thickness and an inverted U-shaped curve for anterior chamber depth. The findings of early lens thinning followed by thickening suggest a two-phase growth of the lens.
Investigative ophthalmology & visual science 10/2009; 51(3):1341-7. · 3.43 Impact Factor
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Tina T Wong,
Peng T Khaw,
Tin Aung,
Paul J Foster,
Hla Myint Htoon,
Francis T S Oen,
Gus Gazzard,
Rahat Husain,
Joe G Devereux,
Darwin Minassian, Say-Beng Tan,
Paul T K Chew,
Steve K L Seah
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ABSTRACT: To report 3-year results of a randomized, controlled trial comparing the use of a single application of 5-fluorouracil (5-FU) with placebo in trabeculectomy surgery.
Prospective, randomized, double-blinded treatment trial.
Two hundred forty-three Asian patients with primary open-angle or primary angle-closure glaucoma undergoing primary trabeculectomy.
One eye of each patient was randomized to receive either intraoperative 5-FU or normal saline (placebo) during trabeculectomy.
Primary outcome measure was the level of intraocular pressure (IOP). Secondary outcomes were progression of visual field loss, rates of adverse events, and interventions after surgery.
Of the 288 eligible patients, 243 were enrolled and 228 completed 3 years follow-up; 120 patients received 5-FU and 123 received placebo. Trial failure, according to predefined IOP criteria, was lower in the 5-FU group compared with the placebo group, although the difference was only significant with a failure criterion of IOP >17 mmHg (P = 0.0154). There was no significant difference in progression of optic disc and/or visual field loss over 36 months between 5-FU and placebo (relative risk [RR], 0.67; 95% confidence interval [CI], 0.34-1.31; P = 0.239). Uveitis occurred more often in the 5-FU-treated group (14/115 [12%] vs 5/120 [4%]; P = 0.032).
This is the first masked, prospective, randomized trial reporting the effect of adjunctive 5-FU in trabeculectomy surgery in an East Asian population. The trial shows that an increased success rate can be achieved for several years after a single intraoperative treatment with 5-FU. We conclude that 5-FU is relatively safe and can be routinely used in low-risk East Asian patients.
The authors have no proprietary or commercial interest in any materials discussed in this article.
Ophthalmology 02/2009; 116(2):175-84. · 5.45 Impact Factor
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ABSTRACT: To determine the impact of visual impairment on health-related quality of life (QoL) measures in adolescents.
School-based, cross-sectional study.
Adolescents aged 11 to 18 years from the Singapore Cohort Study of the Risk Factors for Myopia were analyzed. QoL scores were determined using parallel child-self and parent proxy-report of PedsQL 4.0 Generic Core Scales. Refractive error was measured using the table-mounted autorefractor (model RK5 Canon Inc, Ltd, Tochigiken, Japan) and habitual distance logarithm of the minimal angle of resolution (logMAR) visual acuity charts were used.
Data on 1,249 adolescents and 948 parents were analyzed. The prevalence of better eye presenting visual impairment > 0.3 logMAR was 5.7%. The mean (standard deviation) total, physical, and psychosocial health scores of all adolescents were 83.6 (11.8), 89.9 (11.8), and 80.3 (13.7). Healthy adolescents with visual impairment reported statistically but not clinically lower total (-3.8; 95% confidence interval [CI], -7.1 to -0.5; P = .03), psychosocial (-4.2; 95% CI, -8.1 to -0.3; P = .03), and school functioning scores (-5.5, 95% CI, -10.2 to -0.9; P = .02) than those with normal vision. However, no significant difference was observed in the parent proxy-reported scores between the two groups. Differences in total scores between high (1.9; 95% CI, -0.6 to 4.4) and low-myopes (0.2; 95% CI, -1.3 to 1.6) compared with nonmyopes were not significant. Comparable scores were also reported by hyperopes, astigmatism, and their counterparts, as well as their parents. Concordance between child and parent proxy-report was < 0.07.
Healthy adolescents with visual impairment experienced statistically though not clinically impaired health related QoL, but refractive errors did not appear to have an impact on QoL.
American journal of ophthalmology 01/2009; 147(3):505-511.e1. · 3.83 Impact Factor
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ABSTRACT: In the design of randomised trials in rare cancers, a Bayesian approach has been advocated, which allows for external and subjective information to be formally incorporated. We explore whether this can be extended more generally to allow for smaller trials to be conducted using a case study involving a trial of nasopharyngeal carcinoma. The external information available at various points during the trial is first summarised in the form of 'prior distributions'. Each of these is then combined with the accumulated data from the trial at that point in time to form 'posterior distributions', from which conclusions are drawn. We have argued that such a framework for the design, analysis and interpretation of a randomised trial in the light of external evidence is particularly useful in situations such as trials in rare cancers. But more generally, it may potentially also allow for smaller trials to be conducted. Although, at this point in time, we are hesitant to recommend the full implementation of the Bayesian methodology to modify the (conventionally) planned trial size we submit that a formal synthesis of the external evidence bearing on the question of concern is a valuable exercise in itself.
Contemporary Clinical Trials 04/2008; 29(2):211-9. · 1.81 Impact Factor
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ABSTRACT: Patients with poor performance status and/or are elderly are frequently considered a compromised group at high risk of chemotherapy-related morbidities and less likely to benefit from treatment. We aimed to evaluate tolerability and efficacy of three single-agent regimens in these patients.
Patients with advanced non-small cell lung cancer who had performance status 2/3 and/or were aged 70 and older were randomly assigned to receive gemcitabine, vinorelbine, or docetaxel. Objective response, toxicities, and quality of life were evaluated.
One hundred thirty-five patients were registered, of whom one was ineligible. Of the 134 patients, 43 received gemcitabine, 45 vinorelbine, and 46 docetaxel. The response rate was 16%, 20%, 22% for gemcitabine, vinorelbine, and docetaxel, respectively. The main grade 3/4 toxicities were fatigue (18%) and neutropenia (16%). There was improvement in global health scores, cough, and dyspnea for all treatment groups. The improvement in dyspnea was most marked in patients with performance status 3.
There was no significant advantage of any of the treatment arms over the rest. There was benefit seen with improvement of quality of life in patients who were able to receive more cycles of chemotherapy.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 04/2007; 2(3):230-6. · 4.55 Impact Factor
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ABSTRACT: Double-peaked time distributions of the mortality hazard function have been reported for breast cancer patients from Western populations treated with mastectomy alone. These are thought to reflect accelerated tumour growth at micrometastatic sites mediated by angiogenesis after primary tumour removal as well as tumor dormancy. Similar data are not available for Asian populations. We sought to investigate whether differences exist in the pattern of mortality hazard function between Western breast cancer patients and their Asian counterparts in Singapore, which may suggest underlying differences in tumor biology between the two populations.
We performed a retrospective cohort study of female unilateral breast cancer patients diagnosed in Singapore between October 1994 and June 1999. Data regarding patient demographics, tumour characteristics and death were available. Overall survival curves were calculated using the Kaplan-Meier method. The hazard rate was calculated as the conditional probability of dying in a time interval, given that the patient was alive at the beginning of the interval. The life table method was used to calculate the yearly hazard rates.
In the 2,105 women identified, 956 patients (45.4%) had mastectomy alone. Demographic characteristics were as follows: 86.5% were Chinese, 45.2% were postmenopausal, 38.9% were hormone receptor positive, 54.6% were node negative and 44.1% had high histological grade. We observed a double-peaked mortality hazard pattern, with a first peak in mortality achieving its maximum between years 2 and 4 after mastectomy, and a second large peak in mortality during year 9. Analyses by subgroups revealed a similar pattern regardless of T stage, or node or menopausal status. This pattern was also noted in high-grade tumors but not in those that were well to moderately differentiated. The double-peaked pattern observed in Singaporean women was quantitatively and qualitatively similar to those reported in Western series.
Our study confirms the existence of a double-peaked process in Asian patients, and it gives further support to the tumour dormancy hypothesis after mastectomy.
Breast cancer research: BCR 02/2007; 9(2):R21. · 5.24 Impact Factor
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ABSTRACT: The journal impact factor is often used to judge the scientific quality of individual research articles and individual journals. Despite numerous reviews in the literature criticising such use, in some countries the impact factor has become an outcome measure for grant applications, job applications, promotions and bonuses. The aim of this review is to highlight the major issues involved with using the journal impact factor as a measure of research quality.
A literature review of articles on journal impact factors, science citation index, and bibliometric methods was undertaken to identify relevant articles.
The journal impact factor is a quantitative measure based on the ratio between yearly citations in a particular journal to total citations in that journal in the previous 2 years. Its use as a criterion for measuring the quality of research is biased. The major sources of bias include database problems from the Institute for Scientific Information and research field effects. The journal impact factor, originally designed for purposes other than the individual evaluation of research quality, is a useful tool provided its interpretation is not extrapolated beyond its limits of validity.
Research quality cannot be measured solely using the journal impact factor. The journal impact factor should be used with caution, and should not be the dominant or only factor determining research quality.
Annals of the Academy of Medicine, Singapore 01/2007; 35(12):911-6. · 1.25 Impact Factor
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Statistics in Medicine 11/2006; 25(19):3407-8. · 1.88 Impact Factor
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Statistics in Medicine 10/2006; 25(18):3220-2; author reply 3222-3. · 1.88 Impact Factor
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Statistics in Medicine 07/2006; 25(19):3407 - 3408. · 1.88 Impact Factor
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ABSTRACT: To determine the risk factors of incident myopia in a school-based cohort study in Singaporean children.
A 3-year prospective cohort study was conducted in Singaporean school children aged 7 to 9 years in three schools at entry. Chinese children without myopia at baseline (n = 994) were included in the analysis. The main outcome was incident myopia, defined as spherical equivalent (SE) at least -0.75 D based on cycloplegic autorefraction. Other definitions of incident myopia, at least -0.5 D and at least -1.0 D, were also assessed.
After controlling for school, age, gender, income, reading in books per week and intelligence quotient (IQ) test scores, we found the relative risk (RR) of incident myopia defined as -0.75 D to be 1.55 (95% confidence interval [CI] 1.18-2.04) for two versus no myopic parents. The multivariate RR of myopia for IQ in the third versus first tertile was 1.50 (95% CI, 1.19-1.89). However, the RR of incident myopia was 1.01 (95% CI, 0.97-1.05) for every unit increase in books read per week. Similar results were obtained with definitions of -0.5 and -1.0 D for incident myopia.
These data provide new prospective evidence of essential links between parental myopia, IQ scores and subsequent myopia development. However, reading in books per week was not associated with incident myopia.
Investigative Ophthalmology & Visual Science 06/2006; 47(5):1839-44. · 3.60 Impact Factor
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ABSTRACT: We propose a dose-finding weighted design for an early clinical trial which aims to determine the optimal dose, selected on the basis of both efficacy and toxicity, to be used in patients entering subsequent studies in a drug development process. The goal is to identify the optimal dose, while using a minimal number of subjects. For each dose under test, a decision table is defined with a utility value attached to each possible decision. The relationship between the utility and the target probability for each outcome is shown. A Dirichlet prior is used and we illustrate the process of maximizing the expected utility under the resulting posterior distribution to find the optimal decision at each stage of the trial. We show how this affects the eventual choice of optimal dose in various scenarios. Properties of our design are discussed and compared with a current standard design.
Statistics in Medicine 02/2006; 25(1):3-22. · 1.88 Impact Factor
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ABSTRACT: So far, most Phase II trials have been designed and analysed under a frequentist framework. Under this framework, a trial is designed so that the overall Type I and Type II errors of the trial are controlled at some desired levels. Recently, a number of articles have advocated the use of Bayesian designs in practice. Under a Bayesian framework, a trial is designed so that the trial stops when the posterior probability of treatment is within certain prespecified thresholds. In this article, we argue that trials under a Bayesian framework can also be designed to control frequentist error rates. We introduce a Bayesian version of Simon's well-known two-stage design to achieve this goal. We also consider two other errors, which are called Bayesian errors in this article because of their similarities to posterior probabilities. We show that our method can also control these Bayesian-type errors. We compare our method with other recent Bayesian designs in a numerical study and discuss implications of different designs on error rates. An example of a clinical trial for patients with nasopharyngeal carcinoma is used to illustrate differences of the different designs.
Statistical Methods in Medical Research 11/2005; 14(5):445-56. · 2.44 Impact Factor
