Adult ; Antibodies, Viral ; blood ; Follow-Up Studies ; Hantaan virus ; isolation & purification ; Hemorrhagic Fever with Renal Syndrome ; diagnosis ; Humans ; Immunoglobulin G ; blood ; Immunoglobulin M ; blood ; Male ; Singapore ; Travel

Decision Making ; Humans ; Models, Theoretical ; Public Health ; Risk Assessment

INTRODUCTION: We investigated the epidemiological features of the 2007 dengue outbreak to determine the factors that could have triggered it two years after the previous large outbreak in 2005.

METHODS: All laboratory-confirmed cases of dengue reported during the year, as well as entomological and virological data, were analysed.

RESULTS: A total of 8826 cases including 24 deaths were reported in 2007, giving an incidence of 192.3 cases per 100 000 residents and a case-fatality rate of 0.27%. The median age of the cases was 37 years (interquartile range 25 to 50), with an age range from two days to 101 years, which was higher than the median age of 31 years (interquartile range 20 to 42), with a range from four days to 98 years, in 2005. The overall Aedes premises index in 2007 was 0.68%, lower than the 1.15% observed in 2005. The predominant dengue serotype in 2007 was dengue virus DENV-2 which re-emerged with a clade replacement in early 2007, and overtook the predominant serotype (DENV-1) of 2005. Seroprevalence studies conducted in the three largest outbreak clusters revealed that 73.2% of residents with recent infection were asymptomatic.

DISCUSSION: With the exception of an increase in the median age of the cases, and a change in the predominant dengue serotype, the epidemiological features of the 2007 epidemic were largely similar to those of 2005. Singapore remains vulnerable to major outbreaks of dengue, despite sustained vector control measures to maintain a consistently low Aedes premises index.

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

INTRODUCTIONTo determine the seroepidemiology of dengue virus infection in a representative sample of the adult resident population aged 18 years old to 74 years old in Singapore and to estimate the proportion of asymptomatic dengue infection during the 2004 epidemic.

MATERIALS AND METHODSThe study was based on 4152 stored blood samples collected between September and December 2004 from participants aged 18 years old to 74 years old during the 2004 National Health Survey. Sera were tested for IgG and IgM antibodies using a commercial test kit (PanBio Capture/Indirect ELISA).

RESULTSOf the study population, 59.0% and 2.6% tested positive for dengue IgG (past infection) and IgM/high-titre IgG (recent infection), respectively. Only 17.2% of young adults aged 18 years old to 24 years old were dengue IgG positive. Multivariate analyses showed that older age, Indian ethnicity and male gender were significantly associated with past infection, whereas only age was significantly associated with recent dengue infection. Based on the dengue cases notified during the period of survey, it was estimated that for every 23 individuals recently infected with dengue, only 1 was reported to the health authority as a clinical case.

CONCLUSIONThe Singapore population is highly susceptible to dengue epidemics despite its aggressive Aedes prevention and control programme. The finding of a high proportion of unreported cases due to asymptomatic and subclinical infection poses a challenge for dengue control.

Adolescent ; Adult ; Aedes ; Aged ; Animals ; Confidence Intervals ; Cross-Sectional Studies ; Dengue ; epidemiology ; transmission ; Dengue Virus ; Disease Outbreaks ; Female ; Health Surveys ; Humans ; Immunoglobulin G ; Immunoglobulin M ; Logistic Models ; Male ; Middle Aged ; Mosquito Control ; Multivariate Analysis ; Odds Ratio ; Population Surveillance ; Risk Factors ; Seroepidemiologic Studies ; Singapore ; epidemiology ; Young Adult

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

INTRODUCTIONDengue is a major public health problem in Singapore. Age-specific dengue morbidity rates are highest in the young adult population, unlike in many other Southeast Asian countries where dengue is mainly a paediatric disease. Hence, the World Health Organization (WHO) guidelines on dengue diagnosis and management which were developed using the paediatric experiences, may not be suitable for the management of adult dengue infections.

MATERIALS AND METHODSThe Early DENgue (EDEN) infection and outcome study is a collaborative longitudinal study to investigate epidemiological, clinical, viral and host-specific features of early dengue-infected adults, in an effort to identify new early markers for prognostication. Patients presenting with early undifferentiated fever were included in the study. We carried out an interim analysis to look for early indicators of severe disease.

RESULTSDuring the period of this interim study analysis, 455 febrile patients were recruited. Of these, 133 were confirmed as acute dengue cases based on dengue-specific polymerase chain reaction (PCR) results. There were significant clinical and epidemiological differences between dengue and febrile non-dengue cases. Nine per cent of the dengue cases experienced persistent tiredness, drowsiness and loss of appetite beyond 3 weeks of illness. Quantitation of viral loads using the crossover (Ct) value of real-time RT-PCR correlated with the duration of symptoms. More than half of both primary and secondary dengue cases were hospitalised. There was no dengue-related mortality in this study.

CONCLUSIONThe duration of illness and prolonged symptom duration in 9% of the subjects indicate that the burden of dengue illness is substantially different from other non-dengue febrile illness in our study cohort. Our study also highlights the paucity of early prognostic markers for dengue fever in adults.

Adult ; Antibodies, Viral ; analysis ; Dengue ; diagnosis ; epidemiology ; virology ; Dengue Virus ; genetics ; immunology ; isolation & purification ; Enzyme-Linked Immunosorbent Assay ; Female ; Follow-Up Studies ; Humans ; Male ; Morbidity ; trends ; Prognosis ; RNA, Viral ; analysis ; Retrospective Studies ; Reverse Transcriptase Polymerase Chain Reaction ; Singapore ; epidemiology

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

Background: The PLASMIC score is a convenient tool for predicting ADAMTS13 activity of ＜10%.Lactate dehydrogenase (LDH) is widely used as a marker of haemolysis in thrombotic thrombocytopenic purpura (TTP) monitoring, and could be used as a replacement marker for lysis. We aimed to validate the PLASMIC score in a multi-centre Asia Pacific region, and to explore whether LDH could be used as a replacement marker for lysis. Methods: Records of patients with thrombotic microangiopathy (TMA) were reviewed. Patients’ ADAMTS13 activity levels were obtained, along with clinical/laboratory findings relevant to the PLASMIC score. Both PLASMIC scores and PLASMIC-LDH scores, in which LDH replaced traditional lysis markers, were calculated. We generated a receiver operator characteristics (ROC) curve and compared the area under the curve values (AUC) to determine the predictive ability of each score. Results: 46 patients fulfilled the inclusion criteria, of which 34 had ADAMTS13 activity levels of ＜10%. When the patients were divided into intermediate-to-high risk (scores 5‒7) and low risk (scores 0‒4), the PLASMIC score showed a sensitivity of 97.1% and specificity of 58.3%, with a positive predictive value (PPV) of 86.8% and negative predictive value (NPV) of 87.5%. The PLASMIC-LDH score had a sensitivity of 97.1% and specificity of 33.3%, with a PPV of 80.5% and NPV of 80.0%. Conclusion Our study validated the utility of the PLASMIC score, and demonstrated PLASMIC-LDH as a reasonable alternative in the absence of traditional lysis markers, to help identify high-risk patients for treatment via plasma exchange.

INTRODUCTION: Institutional surgical antibiotic prophylaxis (SAP) guidelines are in place at all public hospitals in Singapore, but variations exist and adherence to guidelines is not tracked consistently. A national point prevalence survey carried out in 2020 showed that about 60% of surgical prophylactic antibiotics were administered for more than 24 hours. This guideline aims to align best practices nationally and provides a framework for audit and surveillance. METHOD: This guideline was developed by the National Antimicrobial Stewardship Expert Panel's National Surgical Antibiotic Prophylaxis Guideline Development Workgroup Panel, which comprises infectious diseases physicians, pharmacists, surgeons and anaesthesiologists. The Workgroup adopted the ADAPTE methodology framework with modifications for the development of the guideline. The recommended duration of antibiotic prophylaxis was graded according to the strength of consolidated evidence based on the scoring system of the Singapore Ministry of Health Clinical Practice Guidelines. RESULTS: This National SAP Guideline provides evidence-based recommendations for the rational use of antibiotic prophylaxis. These include recommended agents, dose, timing and duration for patients undergoing common surgeries based on surgical disciplines. The Workgroup also provides antibiotic recommendations for special patient population groups (such as patients with β-lactam allergy and patients colonised with methicillin-resistant Staphylococcus aureus), as well as for monitoring and surveillance of SAP. CONCLUSION This evidence-based National SAP Guideline for hospitals in Singapore aims to align practices and optimise the use of antibiotics for surgical prophylaxis for the prevention of surgical site infections while reducing adverse events from prolonged durations of SAP.
Humans ; Antibiotic Prophylaxis ; Anti-Bacterial Agents/therapeutic use* ; Methicillin-Resistant Staphylococcus aureus ; Singapore ; Surgeons ; Hospitals, Public