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Biomedical subjects

B C Tai

Publications and source records attributed to B C Tai.

16 recordsLinked to original sources

Ethnicity modifies the association between diabetes mellitus and ischaemic heart disease in Chinese, Malays and Asian Indians living in Singapore.

AIMS/HYPOTHESIS: The aim of the study was to determine whether the risk of ischaemic heart disease (IHD) associated with diabetes mellitus differs between ethnic groups. METHODS: Registry linkage was used to identify IHD events in 5707 Chinese, Malay and Asian Indian participants from three cross-sectional studies conducted in Singapore between the years 1984 and 1995. The study provided a median of 10.2 years of follow-up with 240 IHD events experienced. We assessed the interaction between diabetes mellitus and ethnicity in relation to the risk of IHD events using Cox proportional hazards regression. RESULTS: Diabetes mellitus was more common in Asian Indians. Furthermore, diabetes mellitus was associated with a greater risk of IHD in Asian Indians. The hazard ratio when comparing diabetes mellitus with non-diabetes mellitus was 6.41 (95% CI 5.77-7.12) in Asian Indians and 3.07 (95% CI 1.86-5.06) in Chinese (p = 0.009 for interaction). Differences in the levels of established IHD risk factors among diabetics from the three ethnic groups did not appear to explain the differences in IHD risk. CONCLUSIONS/INTERPRETATION: Asian Indians are more susceptible to the development of diabetes mellitus than Chinese and Malays. When Asian Indians do develop diabetes mellitus, the risk of IHD is higher than for Chinese and Malays. Consequently, the prevention of diabetes mellitus amongst this ethnic group is particularly important for the prevention of IHD in Asia, especially given the size of the population at risk. Elucidation of the reasons for these ethnic differences may help us understand the pathogenesis of IHD in those with diabetes mellitus.

Adult↗

Prevalence and profile of females at risk of eating disorders in Singapore.

INTRODUCTION: The objective of this study was to assess the prevalence of young females at risk of developing eating disorders (ED) and the associated socio-demographical variables. METHODS: A set of self-administered questionnaires consisting of an Eating Attitude Test (EAT), an Eating Disorder Inventory (EDI) and a socio-demographical questionnaire was administered to 4,461 young females. Based on scores for EAT and/or EDI-drive for thinness (EDI-DT) subscale, subjects were categorised into either "normal" (NM) or "at risk" (AR) of ED. RESULTS: Mean age of the subjects was 16.7 years (range 12-26 years). The ethnic composition was 78.8 percent Chinese, 11.7 percent Malay, 6.6 percent Indian and 3 percent other ethnic groups. Prevalence of AR was 7.4 percent (95 percent confidence interval [CI] 6.7-8.2 percent). Mean EAT and EDI-DT scores for AR were significantly higher than that of NM (EAT: mean difference is 22.1, 95 percent CI 20.7-23.4, p-value is less than 0.0001; EDI-DT: mean difference is 10.9, 95 percent CI 10.5-11.4, p-value is less than 0.0001). Female Malays constituted a significantly larger proportion of AR (20.6 percent) as compared to NM (10.9 percent). AR females are more likely to use Malay as a spoken language at home (prevalence rate ratio 1.70, p-value is 0.001) and to be better educated with completion of General Certificate of Education (GCE) "O" levels. However, the parents of AR females are likely to be less well educated (below GCE "A" levels). CONCLUSION: The prevalence of females at risk of developing ED is 7.4 percent. Malay ethnic group, using Malay language at home and the educational levels of both the subjects and their parents appear to be associated with an increased risk for development of ED.

Adolescent↗

MELD may not be the better system for organ allocation in liver transplantation patients in Singapore.

INTRODUCTION: The Model for End-Stage Liver Disease (MELD) score is a good predictor of mortality on the liver transplant waiting list and is the current system of organ allocation in the USA. However, a higher MELD may be associated with poorer outcome post-liver transplantation. The aim of this study was to determine if MELD should be implemented as the system for organ allocation for liver transplantation in Singapore. METHODS: There were 46 adult patients who underwent primary liver transplantation at the National University Hospital, Singapore from January 1996 to December 2002. We applied the MELD score to patients who were transplanted and looked for a correlation with survival post-transplant. Patients were followed-up until the most recent visit or death. Survival analysis was performed using Cox regression and Kaplan-Meier method. RESULTS: The mean age at transplant was 52.7 (SD 2.34) years. The majority of the patients transplanted had Hepatitis B (43 percent). The median MELD score at transplantation was 17 (7-42) and the median Child's score was 11 (6-15). There was a significant correlation between pre-transplant MELD and survival at six months (p-value is 0.037, 95 percent confidence interval [CI] is 1.004-1.13) but not at one year (p-value is 0.065, 95 percent CI is 0.99-1.12). There were no differences in the pre-transplant MELD (odds-ratio [OR] 1, 95 percent CI 0.9-1) as well as survival for patients with and without Hepatitis B (OR 0.72, 95 percent CI 0.22-2.35). CONCLUSION: MELD allows livers to be allocated to the patients with the greatest medical urgency but its influence on post-transplant survival should be further clarified so that post-transplant survival is not compromised.

Female↗

Angiotensin-I converting enzyme insertion/deletion polymorphism and its association with diabetic nephropathy: a meta-analysis of studies reported between 1994 and 2004 and comprising 14,727 subjects.

AIMS/HYPOTHESIS: The ACE insertion/deletion polymorphism has been examined for association with diabetic nephropathy over the past decade with conflicting results. To clarify this situation, we conducted a comprehensive meta-analysis encompassing all relevant studies that were published between 1994 and 2004 and investigated this potential genetic association. METHODS: A total of 14,727 subjects from 47 studies was included in this meta-analysis. Cases (n=8,663) were type 1 or 2 diabetic subjects with incipient (microalbuminuria) or advanced diabetic nephropathy (proteinuria, chronic renal failure, end-stage renal disease). Control subjects (n=6,064) were predominantly normoalbuminuric. RESULTS: No obvious publication bias was detected. Using a minimal-case definition based on incipient diabetic nephropathy, subjects with the II genotype had a 22% lower risk of diabetic nephropathy than carriers of the D allele (pooled odds ratio [OR]=0.78, 95% CI=0.69-0.88). While there was a reduced risk of diabetic nephropathy associated with the II genotype among Caucasians with either type 1 or type 2 diabetes, the association was most marked among type 2 diabetic Asians (Chinese, Japanese, Koreans) (OR=0.65, 95% CI=0. 51-0.83). This OR is significantly different from the OR of 0.90 (95% CI= 0.78-1.04) that was obtained for type 2 diabetic Caucasians (p=0.019). Using a stricter case definition based on advanced diabetic nephropathy, a comparable risk reduction of 24-32% was observed among the three subgroups, although statistical significance was reached only among Asians. CONCLUSIONS/INTERPRETATION: The results of our meta-analysis support a genetic association of the ACE Ins/Del polymorphism with diabetic nephropathy. These findings may have implications for the management of diabetic nephropathy using ACE inhibitors especially among type 2 diabetic Asians.

Case-Control Studies↗

The MELD score may help to determine optimum time for liver transplantation.

BACKGROUND: The model for end-stage liver disease (MELD) score is a good predictor of mortality on the waiting list and short-term survival post liver transplantation. AIM: Our aim was to determine if there is a pretransplant MELD score beyond which liver transplantation is prohibitive. PATIENTS AND METHODS: Forty-six adult patients underwent primary liver transplantation from January 1996 to December 2002. Patients followed to the most recent visit or death underwent survival analysis using Cox regression and Kaplan Meier methods. RESULTS: There was a significant correlation between the pretransplant MELD score and survival at 6 months posttransplant (P=.037 95% CI: 1.004-1.13). Patients with pretransplant MELD score greater than or equal to 32 showed significantly greater mortality compared with those less than 32 (HR 9.18, 95%CI=1.16-72.44). CONCLUSION: Pretransplant MELD may help to determine the optimum time for liver transplantation.

Adult↗

Immunosuppressive therapy in acute myocarditis: an 18 year systematic review.

BACKGROUND: Immunosuppressive therapy is reportedly ineffective in adults with acute myocarditis. AIMS: To systematically review the impact of immunosuppressive therapy on the outcome of acute myocarditis in children. METHODS: A literature search for articles published from 1984 to 2003 was conducted with the following keywords: myocarditis, dilated cardiomyopathy, and immunosuppression. The relevant studies were systematically reviewed and comparison of treatment effect was made by calculating the odds ratio (OR) and confidence interval (CI) using the exact method based on the exact discrete reference distribution. RESULTS: Of the 1470 articles found, only nine studies were eligible. The odds for improvement with immunosuppression was between 4.33 (95% CI 0.52 to 52.23) and 2.7 (95% CI 0.59 to 14.21). Addition of a second immunosuppressive agent to prednisolone only proved effective in one randomised controlled trial (OR 0.09, 95% CI 0.01 to 0.52). Heterogeneity of these studies precluded pooled odds ratio. CONCLUSION: Current data suggest that immunosuppressive therapy does not significantly improve outcomes in children with acute myocarditis and there is insufficient evidence for its routine use. However, statistical power to detect a significant difference in the treatment effect may be limited because of the small number of subjects. This, together with problems of diagnosis, varying treatment practices, and a relative lack of evidence based guidelines would support efforts for a large multicentre, randomised controlled trial to better define the role of immunosuppression in acute myocarditis.

Acute Disease↗

Gemcitabine in metastatic nasopharyngeal carcinoma of the undifferentiated type.

BACKGROUND: We conducted two parallel phase II trials in chemonaïve and previously treated patients with metastatic nasopharyngeal carcinoma (NPC) to evaluate the tumour response, progression-free and overall survival, and toxicity of gemcitabine. PATIENTS AND METHODS: Gemcitabine 1250 mg/m2 was given on days 1 and 8 of a 21-day cycle. Patients with an Eastern Cooperative Oncology Group performance status <2, adequate renal, hepatic and bone marrow function, and radiologically measurable NPC were eligible. RESULTS: Twenty-five chemonaïve and 27 previously treated patients were enrolled. The overall response rate was 28% [95% confidence interval (CI) 14% to 48%] for the chemonaïve and 48% (95% CI 31% to 66%) for previously treated patients. Toxicities greater than or equal to grade 3 occurred in 15 (60%) chemonaïve and 13 (48%) previously treated patients. Neutropenia was uncommon in chemonaïve patients, but occurred in 37% of previously treated patients. The median time to progression was 3.6 months (range 0.9-7.9) for chemonaïve and 5.1 months (0.9-13.1) for previously treated patients. Median overall survival time was 7.2 months (1.4-15.6) and 10.5 months (2.4-15.0) for chemonaïve and previously treated patients, respectively. CONCLUSIONS: Gemcitabine has moderate activity in NPC with minimal toxicity, and is also an effective salvage agent for patients who have failed or progressed after treatment with other agents.

Adult↗

A competing risk approach to the analysis of trials of alternative intra-uterine devices (IUDs) for fertility regulation.

The methods of survival analysis have had a profound influence on the way that studies concerned with the safety and efficacy of intra-uterine devices (IUDs) for fertility control have been designed, conducted, analysed and reported. For example, the Kaplan-Meier technique has been used to summarize the results of controlled clinical trials of alternative devices and the logrank test used to make any comparisons. A particular feature of IUD studies is the large number of possible causes of failure (reasons for discontinuation of the device). These lead to considerations of competing risks, where in this framework, the discontinuations are considered as competing causes of contraceptive failure. In this context, we compare the net and crude probability estimates of discontinuation rates using continuous time and argue for the routine use of the latter. We use data from a randomized multi-centre trialon the long-term safety and efficacy of two IUDs, TCu220C and TCu380A, for illustration.

Contraception↗

Competing risks analysis of patients with osteosarcoma: a comparison of four different approaches.

In failure time studies involving a chronic disease such as cancer, several competing causes of mortality may be operating. Commonly, the conventional statistical technique of Kaplan-Meier, which is only meaningfully interpreted by assuming independence of failure types and the censoring mechanism, is employed in clinical research involving competing risks data. Some authors have advocated the use of a cause-specific cumulative incidence function which takes into account the existence of other events within a competing risks framework, without making any assumption about independence. Lunn and McNeil have proposed an approach based on an extension of the Cox proportional hazards regression, which enables direct comparisons between failure types. We have extended this approach to estimate cause-specific cumulative incidence. As it is often not easy to follow competing risks methodology in the literature, this paper sets out systematically the assumptions made and the steps taken to implement four different methods of analysing competing risks data using cumulative incidence rates or the Kaplan-Meier estimates of cause-specific failure probabilities. The data obtained from a randomized trial of patients with osteosarcoma were used to compare these four approaches. As illustrated using the osteosarcoma data, the estimates of the classical Kaplan-Meier methods have larger numerical values than the cause-specific cumulative incidence. On the other hand, estimates of the cause-specific cumulative incidence rates from the conventional method and the modified Cox method are highly comparable.

Adolescent↗

Randomized clinical trial of the effect of open versus laparoscopically assisted colectomy on systemic immunity in patients with colorectal cancer.

BACKGROUND: Laparoscopic surgery is believed to produce an attenuated metabolic stress response and to have a less dampening effect on the immune response than open surgery. To date, the effect has not been studied in a randomized clinical trial of colorectal cancer. METHODS: The study was a two-armed randomized prospective trial conducted in parallel with the UK Medical Research Council's Conventional versus Laparoscopic-Assisted Surgery in Colorectal Cancer (CLASICC) trial comparing laparoscopically assisted colorectal surgery for left-sided tumours with conventional open surgery. Systemic immunity was assessed by determining the T- and B-cell counts, the CD4 : CD8 ratio, the natural killer cell counts, the immunoglobulin (Ig) G, IgM and IgA levels, and C3 and C4 levels. The white cell phagocytic activity (nitroblue tetrazolium test) was studied before operation and on the third postoperative day. RESULTS: A total of 236 patients were randomized in the immune study between 11 March 1997 and 14 August 1999; 161 had complete preoperative and postoperative assays for the analysis of results. There was no difference in mean response between the two surgical groups for each of the immune parameters studied. The unadjusted difference for the primary endpoint, T-cell count, 3 days after operation was - 1.6 per cent (95 per cent confidence interval - 5.0 to 1.8 per cent). CONCLUSION: There is no difference in the systemic immune response in patients having laparoscopically assisted colectomy compared with those undergoing conventional open surgery for colorectal cancer.

Adult↗

Postpartum intrauterine pressure studies of the uterotonic effect of oral misoprostol and intramuscular syntometrine.

OBJECTIVES: To investigate the effect of oral misoprostol in dosages varying from 200 microg to 800 microg on postpartum uterine contractility and to establish their side effects. DESIGN: A prospective descriptive study. PARTICIPANTS: Fifty-seven women who delivered vaginally after spontaneous labours not requiring augmentation. METHODS: Within 5 minutes of delivery of the placenta, a calibrated Gaeltec catheter with an intrauterine pressure transducer at its tip was inserted transcervically into the uterine cavity. Cumulative uterine activity was recorded for 30 minutes in each woman before administering the oral misoprostol tablets and continued for a further 90 minutes after its administration. Thus each woman acted as her own control regarding changes in uterine contractility. Uterine activity was recorded on a Sonicaid Meridian fetal monitor, which measures active contraction area automatically. The incidence of side effects was also recorded. RESULTS: There was no statistical difference (P = 0.887) in the adjusted mean difference in cumulative uterine activity following all the doses of oral misoprostol, compared with intramuscular syntometrine, the largest difference being seen in oral misoprostol 200 microg (adjusted mean difference -2282 kPas s, 95% CI -7954 to 3390 kPas s). The mean onset of action of oral misoprostol (6.1, SD 2.1 min) was significantly slower than that of intramuscular syntometrine (3.2, SD 1.5 min; P = 0.002), but their durations of action were similar (P = 0.637). In the misoprostol group the commonest side effects were shivering (36%) and a rise in body temperature above 38 degrees C (40%). In the syntometrine group, the most commonly observed side effect was moderate uterine pain (nine out of ten women) and a rise in diastolic blood pressure of 20 mmHg (two out of ten women). CONCLUSION: The results of this study show that oral misoprostol has a definite uterotonic effect on the postpartum uterus. At doses of 200 microg to 400 microg, oral misoprostol has a similar uterotonic effect to intramuscular syntometrine. Higher doses of oral misoprostol are associated with significantly more side effects.

Administration, Oral↗

A review of software for data management, design and analysis of clinical trials.

In clinical trials, subjects are usually entered one at a time, and their responses to treatment monitored sequentially. Regular monitoring of trial progress in the early stages is crucial for accurate reporting of the final results. This paper discusses in detail the principles of quality data management in clinical trials, with specific reference to three clinical data management systems namely, CLINTRIAL, ORACLE CLINICAL and MACRO. All three systems have the essential features for monitoring and processing quality clinical trials data. In terms of functionality, there appears to be no significant advantage of one system over the other. However, to reap the full benefits of sophisticated systems such as these, a good support network and comprehensive training programmes are essential since their day-to-day use demands a high level of technical competence. Basic considerations pertinent to the success of a clinical trial involve not only logistics and data management. Issues relating to the study design are also of primary concern. In this respect, we briefly describe some sample size packages, NQUERY, PEST, POWER, POWER AND PRECISION and SAMPSIZE. Finally, a brief comparison is made with regards to some distinct features of three commonly used statistical packages, namely SPSS, SAS and STATA.

Clinical Trials as Topic↗

Sample size and power calculations for comparing two independent proportions in a 'negative' trial.

Statistical methods for evaluating the adequacy of sample size and power cater mainly to the testing for treatment difference in a 'positive' trial. In biomedical research, the trial can sometimes be postulated as 'negative' to demonstrate that the different treatment groups are statistically equivalent. Herein we describe a computer program to determine the adequacy of sample size and power for comparing two independent proportions in a 'negative' trial. The program is written in MicroSoft QuickBasic Version 4.5, and its executable file is suitable for use as a stand-alone program on a microcomputer.

Clinical Trials as Topic↗

Comparing a sample proportion with a specified population proportion based on the mid-P method.

A common practice for determining whether a sample proportion is statistically different from a specified population proportion is using the exact probability procedure. However, it produces overly conservative confidence intervals and p-values. A stand-alone executable program is written for applying alternative approaches based on the mid-P and bootstrap methods.

Confidence Intervals↗

Quantitative versus qualitative urinalysis for benzoylecgonine in clinical trials for the assessment of cocaine use.

Urinalysis of benzoylecgonine (BE) concentrations is a primary outcome measure for evaluating medications for treating cocaine addiction. Using simulated BE data from a set of simple clinical models, the advantages of quantitative versus qualitative urinalysis were evaluated, as well as the advantages of once-weekly versus thrice-weekly sampling schedules. A 60 percent reduction in cocaine use, either in daily amount or in weekly frequency, was considered clinically significant. Quantitative urinalysis can detect reductions in both amount and frequency, whereas qualitative urinalysis can detect only a decrease in frequency. For quantitative urinalysis, changes are more easily detected when urine is collected three times a week than when it is collected once a week. For qualitative urinalysis, the majority rule analysis for a thrice-weekly sampling schedule yields an artificially high estimate of the percentage of positive samples, whereas a once-weekly schedule gives a highly variable estimate.

Cocaine↗