Timing of commencement of maintenance dialysis and mortality in young and older adults in Singapore.

BACKGROUND: The benefit of early dialysis initiation remains controversial with a paucity of data in Asians. Therefore, we undertook this study to investigate the association between timing of initiation of dialysis and mortality in Singapore. METHODS: The study used data from the Singapore Renal Registry database on 3286 patients with incident end-stage renal disease (ESRD) who commenced maintenance dialysis between January 2008 and December 2011. The data was further linked with the National Death Registry to acquire survival information until December 2013. We classified serum creatinine-based, estimated glomerular filtration rate (eGFR) by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation at the start of dialysis into 3 categories: Early (≥10 ml/min/1.73m2), intermediate (5 to <10 ml/min/1.73m2) and late (<5 ml/min/1.73m2). RESULTS: In the unadjusted analysis, both early and intermediate dialysis initiation groups were at greater risk of death relative to late dialysis (Early: HR = 2.47; Intermediate: HR = 1.54). In the multivariate model, a significant interaction was detected between age and eGFR at dialysis initiation (p = 0.04). Adjusted mortality risk progressively increased with earlier initiation of dialysis for patients aged 18-54 years (p = 0.006) and aged 55 to 64 years (p < 0.001), and no statistically significant difference was observed for patients aged 65 years or older (p = 0.12). CONCLUSIONS: Early versus later initiation of dialysis was associated with significantly higher risk of mortality in Singapore's non-elderly population, and appeared to offer no survival advantage among the elderly.

30-year follow-up study of IgA nephritis in a Southeast Asian population: an evaluation of the Oxford histological classification
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BACKGROUND: In 1985 we reported that 11% of a cohort of 151 patients with IgA nephritis (IgAN) had developed end-stage renal disease (ESRD) after a follow-up period of 5 years. 15 years later, 35% had developed ESRD. METHODS: We retrieved 125 stored renal biopsy paraffin blocks of the original cohort. From these, 102 patients were included in the present study and scored according to the Oxford classification as 21 specimens with less than 8 glomeruli were excluded and in 2 others, tissue samples were too tiny for a re-block. ESRD was ascertained by linking the study cohort to the Singapore Renal Registry at the National Registry of Diseases Office. RESULTS: Renal survival curves for each of the Oxford MEST lesions: endocapillary proliferation (E) (p < 0.04), segmental glomerulosclerosis (S) (p < 0.05), tubular atrophy/interstitial fibrosis (p < 0.0001) were significantly associated with ESRD. Mesangial hypercellularity, less commonly associated with progressive chronic kidney disease (CKD) in the study, was independently associated with ESRD at 30 years (p < 0.03). In this cohort, E and S were associated with lower eGFR at presentation and doubling of serum creatinine in the first 5 years. This study's initial 5 years was representative of the "natural history" of IgAN since no renin-angiotensin system (RAS) blockers or immunosuppression were administered. This represents the early phase of disease progression. E and S may be considered "early disease activity predictors". CONCLUSION: Mesangial hypercellularity and tubular atrophy/interstitial fibrosis (M1 and T1/T2 lesion) of the Oxford classification independently predicted long term ESRD.
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Calcium intake is not related to breast cancer risk among Singapore Chinese women.

There is experimental evidence that calcium protects against breast cancer development. Prospective epidemiologic studies supporting a protective effect of calcium on breast cancer risk have mainly been limited to Western populations. We examined the association between calcium intake and breast cancer risk in the Singapore Chinese Health Study, a large population-based prospective cohort. Calcium intake and supplement use was assessed by in-person interviewer using a validated food frequency questionnaire. After a mean follow-up of 14.2±3.5 years, 823 cohort participants developed invasive breast cancer. Multivariate proportional hazards regression models were fitted to examine the associations between calcium intake and breast cancer risk. Vegetables were the primary food source of calcium in this study population, followed by dairy products, grains and soy foods. Calcium intake was not associated with breast cancer risk, comparing highest quartile (>345.6 mg/1,000 kcal/day) to lowest quartile (<204.5 mg/1,000 kcal/day) of intake. There was no evidence of effect modification by menopausal status, body mass index, dietary vitamin D or stage of disease at diagnosis. Our findings do not support a hypothesis for calcium in breast cancer chemoprevention, contrary to findings from previous studies among Western populations with higher calcium intake primarily from dairy products and supplements.

Anxiety and depression, chronic physical conditions, and quality of life in an urban population sample study.

OBJECTIVE: No previous studies have empirically demonstrated a multiplicative interactive effect of anxiety disorders and/or depression (ADD) and chronic medical conditions on quality of life (QOL). We hypothesized that QOL impairment was worsened by the presence of ADD and medical co-morbidity, more than when it was with either medical co-morbidity alone or ADD alone. METHODS: Complete data of 2,801 participants from the National Mental Health Survey of Adults in Singapore were analyzed, using SCAN diagnoses of anxiety disorders and depression, self-reports of chronic medical conditions, and SF-12 measures of QOL (Mental Component Summary, MCS, and Physical Component Summary, PCS). RESULTS: Persons diagnosed with ADD (compared to those without) had considerably more medical co-morbidities (59 vs. 33%, p < 0.001). In multiple regression analyses, ADD (vs. no ADD) was associated with lower PCS (b = -1.013, p = 0.045) and MCS scores (b = -9.912, p < 0.001), as was number of medical co-morbidities (0, 1-2, 3 +), PCS scores (b = -2.058, p < 0.001) and MCS scores (b = -1.138, p < 0.001). There were significant interactive effects of medical co-morbidities and ADD on PCS (p < 0.001), and MCS (p = 0.086), suggesting that the negative effects of medical conditions on quality of life was aggravated non-additively by the co-morbid presence of ADD, and vice versa. CONCLUSION: The individual effects of medical and psychiatric morbidity on functional status and quality of life were considerably worse when both were present in the same individual. Future studies should examine the impact of identifying and treating anxiety and depressive disorders in patients with medical problems for better outcomes.

Health beliefs and help seeking for depressive and anxiety disorders among urban Singaporean adults.

OBJECTIVE: This study examined whether help seeking for mental problems was predicted by beliefs about mental illness and services and by family and social support. METHODS: Singaporean adults (N= 2,801) were interviewed with the Schedule for Clinical Assessment in Neuropsychiatry and with questions on mental health status, beliefs about the curability of mental illness, embarrassment and stigma, ease of discussing mental problems, effectiveness and safety of treatment, and trust in professionals. RESULTS: Although 10% of respondents had a depressive or anxiety disorder or combination, only 3% acknowledged having mental problems, 5% rated their mental health as fair or poor, and 6% sought help for their mental health problems. Help seeking was predicted by poor self-rated mental health and acknowledged mental illness but not by health beliefs and social support. CONCLUSIONS: Self-rated mental health status was predictive of help seeking, but other health beliefs and social support were neither strong nor robust predictors.

Longitudinal Community-Based Study of QT Interval and Mortality in Southeast Asians.

INTRODUCTION: The prognostic impact of QT interval prolongation has not been well studied in healthy Asians. We investigated the association between the QT interval with mortality and cardiovascular events in a healthy Southeast Asian population. METHODS: The QT interval corrected for heart rate using the Bazett's formula (QTc) was measured in 2536 (825 men, mean age 65.7±7.5 years) Singaporean adults free of cardiovascular disease in the population-based Singapore Longitudinal Ageing Study. Outcomes were all-cause mortality and incident cardiovascular events (cardiovascular mortality, myocardial infarction (MI) and/or stroke). RESULTS: Over a mean 7.78 years (19695 person-years) of follow-up, there were 202 deaths (45 from cardiovascular causes), 62 cases of myocardial infarction and 64 cases of stroke. Adjusting for age, sex, and cardiovascular risk factors, QTcB prolongation remained independently associated with increased all-cause mortality (HR(per standard deviation) 1.27 (1.10-1.48), p = 0.0015), as well as increased risk of cardiovascular events (HR 1.20 (1.01-1.43), p = 0.0415) and MI/stroke (HR 1.22 (1.01-1.47), p = 0.0455), but not cardiovascular mortality alone (HR 1.05 (0.77-1.44), p = 0.7562). CONCLUSIONS: We provide the first community-based estimates of the independent association of QT prolongation with all-cause mortality and cardiovascular events in Southeast Asians.

Body mass index and risk of pancreatic cancer in a Chinese population.

Few studies have examined the association between body mass index (BMI: kg/m(2)) and pancreatic cancer risk in Asian populations. We examined this relationship in 51,251 Chinese men and women aged 45-74 who enrolled between 1993 and 1998 in the population based, prospective Singapore Chinese Health Study. Data were collected through in-person interviews. By December 31, 2011, 194 cohort participants had developed pancreatic cancer. A Cox proportional hazards model was used to estimate hazard ratios (HR) and their 95% confidence intervals (95% CI). We hypothesized the association between BMI and pancreatic cancer risk may vary by smoking status (ever v. never) and there was evidence for this as the interaction between BMI and smoking status was significant (p = 0.018). Among ever smokers, being classified as underweight (BMI <18.5 kg/m(2)), was associated with a significantly elevated risk of pancreatic cancer relative to smokers with a BMI of 21.5-24.4 kg/m(2) (HR = 1.99, 95% CI  =  1.03-3.84). This association was strengthened after exclusion of the first three years of follow-up time. Among never smokers, there was no association between BMI and pancreatic cancer risk. However, after excluding pancreatic cancer cases and person-years in the first three years of follow-up, never smokers with a BMI ≥ 27.5 kg/m(2) showed a suggestive increased risk of pancreatic cancer relative to never smokers with a BMI of 21.5-24.4 kg/m(2) (HR  =  1.75, 95% CI  =  0.93-3.3). In conclusion, Singaporean Chinese who were underweight with a history of smoking had an increased risk of developing pancreatic cancer, whereas there was no significant association between BMI and pancreatic cancer in never smokers.

Evaluation of the National Cervical Cancer Screening Programme in Singapore.

INTRODUCTION: A retrospective observational study was performed to evaluate the effectiveness of CervicalScreen Singapore (CSS), a National Cervical Cancer Screening Programme. METHODS: National trends on incidence, mortality of cervical cancer and carcinoma in situ of the cervix before and after the launch of CSS were examined. Linear regression was used to calculate the average annual percentage change in age-standardised incidence and mortality rates. We also examined the operational measures of CSS, such as the women who joined the CSS programme and the diagnostic accuracy of Pap smears. The study was confined to women who consented to join CSS at government-funded polyclinics. RESULTS: Nationally, there was a greater decline in the age-standardised incidence and mortality rates in the period 2004-2008 as compared to the period 1987-2003. Under CSS, a total of 99,759 Pap smears were performed on 81,087 women in the period 2004-2008. However, the number of first screens decreased from 18,434 in 2004 to 11,624 in 2008. Among women aged 25-69 years who had their first Pap smear screening and who were recommended for routine rescreen in three years, 10% had a subsequent rescreen within three years. Overall, the CSS programme was able to detect 0.37 invasive cancers per 1,000 screens in women aged 25-69 years. CONCLUSION: The CSS programme has contributed to a decline in the mortality and incidence of cervical cancer in Singapore. However, the challenges of increasing the screening uptake among eligible women need to be addressed.

Isotretinoin is safe and efficacious in Asians with acne vulgaris.

BACKGROUND: Oral isotretinoin is effective for acne vulgaris but concerns remain regarding its adverse effects. OBJECTIVES: This study aims to evaluate the safety and efficacy of isotretinoin for acne vulgaris in Asian patients. METHODS: We conducted a 4-year retrospective study on all patients with acne vulgaris treated with isotretinoin, between January 2005 and December 2008 at the National Skin Centre in Singapore. Medical records were reviewed for information on patient demographics, acne severity, isotretinoin dose, duration, adverse effects and outcome. RESULTS: There were 2,255 patients, with a mean age of 22.5 years, male:female ratio of 2.5:1 and 82.3% being Chinese. The mean starting dose of isotretinoin was 0.4 mg/kg and on average, patients received 7.8 months of treatment at a mean dose of 0.5 mg/kg. Mean total cumulative dose was 95.6 mg/kg. Vast majority (93.9%) achieved complete remission or substantial improvement. Thirty-eight (2.2%) and 24 patients (2.7%) developed elevated serum levels of alanine and aspartate aminotransferases subsequent to treatment. There were 194 (12.1%) and 80 (4.8%) patients who developed hyperlipidaemia and hypertriglyceridaemia respectively. Isotretinoin was generally well-tolerated, with 6.4% (n = 145) discontinuing due to side-effects. CONCLUSIONS: This study reaffirms the overall safety and efficacy of oral isotretinoin in Asian patients with acne vulgaris.

Place of death and its determinants for patients with cancer in Singapore: an analysis of data from the Singapore Cancer Registry, 2000-2009.

AIMS: To describe the place of death for patients with cancer in Singapore from 2000 to 2009, and determinants of death at home and in in-patient hospice compared to death in hospital. METHOD: Cross-sectional analysis of all patients registered with the Singapore Cancer Registry who had died in the study period (N=52120). Places of death were grouped as homes, in-patient hospices, hospitals and others. For determinants of death at home and in in-patient hospice, covariates adjusted for in logistic regression analyses were age group, gender, ethnic group, primary tumour site, stage at diagnosis, duration and cause of death. RESULTS: In the 10-year period, 52.9% of patients with cancer had died in the hospital, 30.3% died at home and 10.7% in in-patient hospice. Determinants of death at home were older age, female (odds ratio OR 1.23, 95% confidence interval, CI 1.17-1.29), Malay (OR 2.28, 95% CI 2.13-2.44), cancers of the colo-rectum, liver, stomach, pancreas and nasopharynx (compared to lung cancer), duration of illness of 1-5 years (OR 1.40, 95% CI 1.34-1.48), primary cause of death being 'neoplasms' (OR 2.97, 95% CI 2.79-3.17). Determinants of death in in-patient hospice were older age, distant metastasis (OR 1.35, 95% CI 1.21-1.50) and primary cause of death being 'neoplasms' (OR 20.07, 95% CI 16.05-25.09). CONCLUSION: Knowledge about place of death and its determinants will facilitate the planning of healthcare services to enable patients with terminal cancer to die at home and in in-patient hospices, thereby avoiding inappropriate hospitalization at the end of life.