Humans ; Kidney Failure, Chronic ; epidemiology ; physiopathology ; therapy ; Singapore ; epidemiology

Translational research (TR) can be defined as research where a discovery made in the laboratory (bench) can be applied in the diagnosis, treatment or prevention of a disease. Examples of medical discoveries contributing to translational medicine (TM) include the isolation of insulin by Banting (Nobel Laureate, 1923), the discovery of penicillin by Alexander Fleming (Nobel Laureate, 1945) and recently the discovery of the role of bacterium Helicobacter pylori in the causation of gastritis and peptic ulcer by Marshall and Warren (Nobel Laureates, 2005). Clinical research (CR) would be a more appropriate term for the bulk of research work undertaken by doctors. CR embraces both clinical based and laboratory-based research. The terminology "bedside to bench" applies more to CR as opposed to "bench to bedside" in the case of TR. But regardless of who does it, as long as the discovery can be translated to the bedside and results in improvement in patient care it can be considered a contribution to TM. Our work spans a 30-year period, involving laboratory-based research, clinical trials and genomics of IgA nephritis (Nx). This is a series of work to elucidate the pathogensis and therapy of IgANx. Plasma beta-thromboglobulin (BTG) an in-vivo index of platelet aggregation and anti-thrombin III increase due to a constant thrombogenecity resulting from platelet degranulation formed the basis for anti-platelet and low-dose warfarin therapy. A study of the natural history of IgANx revealed 2 courses, a slowly progressive course with end-stage renal failure (ESRF) at 7.7 years and a more rapid course at 3.3 years. Triple therapy (cyclophosphamide, persantin and low-dose warfarin) delayed progression to ESRF by about 8 years and for some patients up to 20 years. Documentation of abnormal suppressor T cell function provided the basis for immune therapy. Four patterns of proteinuria were present in IgANx and it is the quality and not so much the quantity of proteinuria which determined the prognosis. Low molecular weight proteinuria was a bad prognostic marker. A controlled therapeutic trial using ACEI/ATRA showed that therapy decreases proteinuria, improves renal function and converts non-selective to selective proteinuria. Subsequent work confirmed that it was the ATRA, not the ACEI which contributed to improved renal function. Individual anti proteinuria response to ATRA varies depending on ACE gene polymorphism. We found that the II genotype of the ACE gene was renoprotective and patients with this genotype had significantly reduced incidence of ESRF compared to those with the DD genotype. Patients responsive to ATRA therapy can retard progression to ESRF by up to 32 years. Mild renal failure can be reversed with possible regression of glomerulosclerosis because of glomerular remodelling by ATRA.
Disease Progression ; Evidence-Based Medicine ; history ; Genetic Predisposition to Disease ; Genomics ; history ; Glomerulonephritis, IGA ; genetics ; history ; History, 20th Century ; History, 21st Century ; Humans ; Polymorphism, Genetic ; Singapore

This paper explains some of the difficulties doctors face when taking up a career in research. It describes the efforts by the government and the Ministry of Health (MOH) to nurture the Clinician Scientist Programme. The nature of research and the mindset of clinicians who are passionate about research are explored and the reasons which drive some of them to pursue a research career. It discusses the need to have structured training for research and how continuing research education is necessary for the researcher. The paper discusses the goals for research and how we can achieve better research outcomes and the importance of good mentorship. It suggests ways to engage more doctors in research in the restructured hospitals by overcoming some of the problems they encounter. Finally, it relates the Biomedical Science initiative of the government through the National Research Foundation and the various programmes in Translational Clinical Research available for clinicians who are keen on a research career.
Career Choice ; Goals ; Humans ; Physicians ; Research Personnel ; supply & distribution ; Singapore ; Translational Medical Research ; education ; manpower

Caregivers are important in post-stroke rehabilitation, but little work has been done on the caregivers of stroke survivors in Asian cultures. We examined the association between patient profile (age, gender, socioeconomic status, functional level, religion, and ethnicity) and caregiver availability, number of potential caregivers and primary caregiver identity amongst Singaporean community hospitals' stroke patients. Data was obtained from all Singaporean community hospitals from 1996-2005. 3796 patients fulfilled inclusion criteria. Mixed logistic regression identified independent predictors of caregiver availability and primary caregiver identity. Mixed Poisson modelling identified independent predictors of the number of caregiver(s). Among recent stroke survivors, 95.8% (3640/3796) had potential caregivers, of which 94.2% (3429/3640) had identified primary caregivers. Of the latter, 41.2% relied on live-in hired help (foreign domestic workers-FDWs), 27.6% on spouses and 21.6% on first-degree relatives. Independent patient factors associated with caregiver availability and number were older, female, married, higher socioeconomic status, having a religion and lower functional level at admission. Independent patient factors associated with FDW caregivers were older age, female, Chinese compared to Malay, with higher socioeconomic class and lower functional level at admission. Caregiver availability for post-stroke patients in Singapore community hospitals is relatively high, with heavy dependence on FDWs.

Apart from clinical, histological and biochemical indices, genomics are now being employed to unravel the pathogenetic mechanisms in the disease progression of IgA nephritis (IgAN). The results of angiotensin converting enzyme (ACE) gene polymorphism have been controversial. Those patients with the DD genotype seem to have a poorer prognosis. However, with high dose angiotensin receptor blocker (ARB) therapy, the ACE gene polymorphism status of a patient may no longer be a matter for concern as those with the DD genotype would also respond favourably to high dose ARB therapy. Association studies with gene sequencing and haplotypes have suggested that multiple genes are involved in the pathogenesis of IgAN. Some workers have reported a synergistic effect in the combined analysis of AGT-M235T and ACE I/D polymorphism. With the use of deoxyribo nucleic acid (DNA) microarray, tens of thousands of gene expressions genome-wide can be examined together simultaneously. A locus of familial IgAN has been described with strong evidence of linkage to IgAN1 on chromosome 6q22-23. Two other loci were reported at 4q26-31 and 17q12-22. DNA microarray techniques could also help in the identification of specific pathogenic genes that are up- or down-regulated and this may allow genome wide analyses of these genes and their role in the pathogenesis and progression of IgAN. Recently, using genome-wide association studies (GWAS) more loci for disease susceptibility for IgAN have been identified at 17p13, 8p23, 22q12, 1q32 and 6p21.
Angiotensin Receptor Antagonists ; administration & dosage ; Disease Progression ; Dose-Response Relationship, Drug ; Genomics ; methods ; Glomerulonephritis, IGA ; drug therapy ; genetics ; pathology ; Haplotypes ; Humans ; Molecular Sequence Data ; Polymorphism, Single Nucleotide

INTRODUCTIONThis paper presents the results of a community survey on urinary abnormalities which covered 1/80th of the population of Singapore in 1975. These findings were compared with the data from the Singapore National Service Registrants in 1974 as well as data from a recent survey in Singapore and that of other Asian and Western countries.

MATERIALS AND METHODSThe study covered 18,000 persons aged 15 years and above, representing a sampling fraction of 1/80th of the population. A total of 16,808 respondents attended the field examination centres, of whom 16,497 had their urine sample tested representing 92.7% of the sample population.

RESULTSIn the dipstick urine testing at the field examination centres, 769 subjects (4.6%) were found to have urinary abnormalities. Two hundred and eighty-two (36.7%) of these 769 subjects were found to have urinary abnormalities based on urine microscopy constituting a prevalence of 1.71%. The prevalence of proteinuria was 0.63% and for both haematuria and proteinuria was 0.73%. The prevalence for hypertension was 0.43% and renal insufficiency was 0.1%.

DISCUSSIONThe consensus is that routine screening for chronic kidney disease (CKD) in the general population is not cost effective as the yield is too low. Whilst, most studies showed that screening of the general population was not cost effective, it has been suggested that screening for targeted groups of subjects could help to identify certain risk groups who may benefit from early intervention to prevent or retard the progression of CKD.

CONCLUSIONThe prevalence of urinary abnormalities in Singapore has remained the same, now and three decades ago.

Adult ; Aged ; Aged, 80 and over ; Female ; Hematuria ; epidemiology ; pathology ; Humans ; Male ; Middle Aged ; Prevalence ; Proteinuria ; epidemiology ; pathology ; Renal Insufficiency, Chronic ; epidemiology ; pathology ; Risk Assessment ; Singapore ; epidemiology ; Urinalysis ; Urinary Tract Infections ; epidemiology ; Young Adult

INTRODUCTIONLittle data is available on community hospital admissions. We examined the differences between community hospitals and the annual trends in sociodemographic characteristics of all patient admissions in Singaporean community hospitals over a 10- year period from 1996 to 2005.

MATERIALS AND METHODSData were manually extracted from medical records of 4 community hospitals existent in Singapore from 1996 to 2005. Nineteen thousand and three hundred and sixty patient records were examined. Chisquare test was used for univariate analysis of categorical variables by type of community hospitals. For annual trends, test for linear by linear association was used. ANOVA was used to generate beta coefficients for continuous variables.

RESULTSMean age of all patient admissions has increased from 72.8 years in 1996 to 74.8 years in 2005. The majority was Chinese (88.4%), and female (58.1%) and admissions were mainly for rehabilitation (88.0%). Almost one third had foreign domestic workers as primary caregivers and most (73.5%) were discharged to their own home. There were significant differences in socio-demographic profile of admissions between hospitals with one hospital having more patients with poor social support. Over the 10-year period, the geometric mean length of stay decreased from 29.7 days (95% CI, 6.4 to 138.0) to 26.7 days (95% CI, 7.5 to 94.2), and both mean admission and discharge Barthel Index scores increased from 41.0 (SD = 24.9) and 51.8 (SD = 30.0), respectively in 1996 to 48.4 (SD = 24.5) and 64.2 (SD = 27.3) respectively in 2005.

CONCLUSIONThere are significant differences in socio-demographic characteristics and clinical profile of admissions between various community hospitals and across time. Understanding these differences and trends in admission profiles may help in projecting future healthcare service needs.

Aged ; Aged, 80 and over ; Analysis of Variance ; Confidence Intervals ; Diagnosis ; Female ; Hospitals, Community ; Humans ; Male ; Medical Records ; statistics & numerical data ; Middle Aged ; Odds Ratio ; Patient Admission ; statistics & numerical data ; trends ; Singapore ; Social Class