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1.
Environ Int ; 189: 108803, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38870578

ABSTRACT

BACKGROUND: Exposure to ambient air pollution is associated with a significant number of deaths. Much of the evidence associating air pollution with adverse effects is from North American and Europe, partially due to incomplete data in other regions limiting location specific examinations. The aim of the current paper is to leverage satellite derived air quality data to examine the relationship between ambient particulate matter and all-cause and cause-specific mortality in Asia. METHODS: Six cohorts from the Asia Cohort Consortium provided residential information for participants, recruited between 1991 and 2008, across six countries (Bangladesh, India, Iran, Japan, South Korea, and Taiwan). Ambient particulate material (PM2·5) levels for the year of enrolment (or 1998 if enrolled earlier) were assigned utilizing satellite and sensor-based maps. Cox proportional models were used to examine the association between ambient air pollution and all-cause and cause-specific mortality (all cancer, lung cancer, cardiovascular and lung disease). Models were additionally adjusted for urbanicity (representing urban and built characteristics) and stratified by smoking status in secondary analyses. Country-specific findings were pooled via random-effects meta-analysis. FINDINGS: More than 300,000 participants across six cohorts were included, representing more than 4-million-person years. A positive relationship was observed between a 5 µg/m (Dockery et al., 1993) increase in PM2·5 and cardiovascular mortality (HR: 1·06, 95 % CI: 0.99, 1·13). The additional adjustment for urbanicity resulted in increased associations between PM2.5 and mortality outcomes, including all-cause mortality (1·04, 95 % CI: 0·97, 1·11). Results were generally similar regardless of whether one was a current, never, or ex-smoker. INTERPRETATION: Using satellite and remote sensing technology we showed that associations between PM2.5 and all-cause and cause-specific Hazard Ratios estimated are similar to those reported for U.S. and European cohorts. FUNDING: This project was supported by the Health Effects Institute. Grant number #4963-RFA/18-5. Specific funding support for individual cohorts is described in the Acknowledgements.


Subject(s)
Air Pollutants , Air Pollution , Environmental Exposure , Particulate Matter , Humans , Particulate Matter/analysis , Asia , Environmental Exposure/statistics & numerical data , Environmental Exposure/adverse effects , Male , Cohort Studies , Female , Air Pollution/statistics & numerical data , Air Pollution/adverse effects , Air Pollutants/analysis , Middle Aged , Adult , Cardiovascular Diseases/mortality , Aged , Neoplasms/mortality , Lung Neoplasms/mortality , Lung Diseases/mortality , Proportional Hazards Models , Cause of Death
2.
Eur Arch Paediatr Dent ; 22(6): 1033-1040, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34227054

ABSTRACT

PURPOSE: This qualitative study aimed to understand parental perception of (1) sugar-sweetened beverages (SSB) and implications of SSB on health; (2) their role in shaping their children's consumption of SSB; (3) the influences on SSB consumption of their children; and (4) potential government policies targeted at controlling SSB consumption. METHODS: English-speaking parents of pre-schoolers aged 2-6 years were recruited. Semi-structured interviews based on the knowledge, attitude, practice framework were conducted, and transcripts were subjected to thematic analysis based on inductive approaches. Recruitment continued until data saturation was reached. RESULTS: Twenty parents participated in the study and themes addressing the objectives identified. (1) There were misconceptions regarding the healthfulness of certain non-packaged SSB such as traditional remedies and juices. Some were unaware about the association between SSB and dental caries. (2) The need to reduce and restrict sugar consumption for overall and oral health reasons was well-recognised, but the extent of control varied. (3) Multiple stakeholders including pre-schools, grandparents and domestic helpers were involved in shaping children's diet. Children's sugar intake was also influenced by environmental factors, such as the ubiquitously available SSB, targeted marketing and high cost of healthy alternatives. (4) Participants were less accepting towards SSB taxation than the ban of SSB sales. CONCLUSION: Despite the awareness of the types of SSBs and the general/oral health implications of sugar consumption, misconceptions exist. Although most parents possessed the knowledge and attitude, this did not translate into the practice of reducing sugar consumption in their children. There was no SSB reduction policy that had overwhelming acceptability.


Subject(s)
Dental Caries , Sugar-Sweetened Beverages , Beverages , Child , Child, Preschool , Dental Caries/etiology , Dental Caries/prevention & control , Humans , Parents , Police
3.
J Econ Ageing ; 142019.
Article in English | MEDLINE | ID: mdl-31857943

ABSTRACT

Singapore is one of the fastest-aging populations due to increased life expectancy and lowered fertility. Lifestyle changes increase the burden of chronic diseases and disability. These have important implications for social protection systems. The goal of this paper is to model future functional disability and healthcare expenditures based on current trends. To project the health, disability and hospitalization spending of future elders, we adapted the Future Elderly Model (FEM) to Singapore. The FEM is a dynamic Markov microsimulation model developed in the US. Our main source of population data was the Singapore Chinese Health Study (SCHS) consisting of 63,000 respondents followed up over three waves from 1993 to 2010. The FEM model enables us to investigate the effects of disability compounded over the lifecycle and hospitalization spending, while adjusting for competing risk of multi-comorbidities. Results indicate that by 2050, 1 in 6 elders in Singapore will have at least one ADL disability and 1 in 3 elders will have at least one IADL disability, an increase from 1 in 12 elders and 1 in 5 elders respectively in 2014. The highest prevalence of functional disability will be in those aged 85 years and above. Lifetime hospitalization spending of elders aged 55 and above is US$24,400 (30.2%) higher among people with functional disability compared to those without disability. Policies that successfully tackle diabetes and promote healthy living may reduce or delay the onset of disability, leading to potential saving. In addition, further technological improvements may reduce the financial burden of disability.

4.
Diabet Med ; 33(3): 332-9, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26514089

ABSTRACT

AIM: To study prospectively the ethnic-specific risks of cardiovascular disease, end-stage renal disease and all-cause mortality in patients with Type 2 diabetes mellitus among native Asian subpopulations. METHODS: A total of 2337 subjects with Type 2 diabetes (70% Chinese, 17% Malay and 13% Asian Indian) were followed for a median of 4.0 years. Time-to-event analysis was used to study the association of ethnicity with adverse outcomes. RESULTS: Age- and gender-adjusted hazard ratios for cardiovascular disease in ethnic Malay and Asian Indian subjects were 2.01 (1.40-2.88; P<0.0001) and 1.60 (1.07-2.41; P=0.022) as compared with Chinese subjects. Adjustment for conventional cardiovascular disease risk factors, including HbA1c , blood pressure and lipid profile, slightly attenuated the hazards in Malay (1.82, 1.23-2.71; P=0.003) and Asian Indian subjects (1.47, 0.95-2.30; P=0.086); However, further adjustment for baseline renal function (estimated GFR) and albuminuria weakened the cardiovascular disease risks in Malay (1.48, 0.98-2.26; P=0.065) but strengthened that in Asian Indian subjects (1.81, 1.14-2.87; P=0.012). Competing-risk regression showed that the age- and gender-adjusted sub-distribution hazard ratio for end-stage renal disease was 1.87 (1.27-2.73; P=0.001) in Malay and 0.39 (0.18-0.83; P=0.015) in Asian Indian subjects. Notably, the difference in end-stage renal disease risk among the three ethnic groups was abolished after further adjustment for baseline estimated GFR and albuminuria. There was no significant difference in risk of all-cause mortality among the three ethnic groups. CONCLUSIONS: Risks of cardiovascular and end-stage renal diseases in native Asian subjects with Type 2 diabetes vary substantially among different ethnic groups. Differences in prevalence of diabetic kidney disease may partially explain the ethnic disparities.


Subject(s)
Asian People/statistics & numerical data , Cardiovascular Diseases , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/ethnology , Diabetes Mellitus, Type 2/mortality , Health Status Disparities , Kidney Failure, Chronic , Adult , Aged , Cardiovascular Diseases/ethnology , Cardiovascular Diseases/etiology , Cardiovascular Diseases/mortality , Cause of Death , Diabetic Nephropathies/complications , Diabetic Nephropathies/ethnology , Diabetic Nephropathies/mortality , Ethnicity/statistics & numerical data , Female , Humans , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/ethnology , Kidney Failure, Chronic/mortality , Male , Middle Aged , Risk Factors
5.
Qual Life Res ; 24(9): 2163-71, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25800727

ABSTRACT

BACKGROUND: This study aimed to identify factors associated with the health-related quality of life (HRQOL) of multiethnic Asian end-stage renal disease (ESRD) patients treated with dialysis. The role of dialysis modality was also explored. METHODS: Data used in this study were from two cross-sectional surveys of Singaporean ESRD patients on haemodialysis (HD) or peritoneal dialysis (PD). In both surveys, participants were assessed using the kidney disease quality of life (KDQOL) instrument and questions assessing socio-demographic characteristics. Clinical data including co-morbidity (measured by Charlson comorbidity index [CCI]), albumin level, haemoglobin level, and dialysis-related variables (e.g. dialysis vintage and dialysis adequacy) were retrieved from medical records. The 36-item KDQOL (KDQOL-36) was used to generate three summary scores (physical component summary [PCS], mental component summary [MCS] and kidney disease component summary [KDCS]) and two health utility scores (Short Form 6-dimension [SF-6D] and EuroQol 5-dimension [EQ-5D]). Linear regression analysis was performed to examine the association of factors with each of the HRQOL scale scores. RESULTS: Five hundred and two patients were included in the study (mean age 57.1 years; male 52.4 %; HD 236, PD 266). Mean [standard deviation (SD)] PCS, MCS and KDCS scores were 37.9 (9.7), 46.4 (10.8) and 57.6 (18.1), respectively. Mean (SD) health utility score was 0.66 (0.12) for SF-6D and 0.60 (0.21) for EQ-5D. In multivariate regression analysis, factors found to be significantly associated with better HRQOL included: young (<45 years) or old age (>60 years), low CCI (<5), high albumin (≥37 g/l) and high haemoglobin (≥11 g/dl) with PCS; long dialysis vintage (≥3.5 years) with MCS; old age, Malay ethnicity and PD modality with KDCS; low CCI, high albumin and high haemoglobin with EQ-5D and high albumin with SF-6D. CONCLUSIONS: Clinical characteristics are better predictors of HRQOL in ESRD patients than socio-demographics in Singapore. Dialysis modality has no impact on the health utility of those patients.


Subject(s)
Kidney Failure, Chronic/psychology , Peritoneal Dialysis/psychology , Quality of Life/psychology , Renal Dialysis/psychology , Adult , Aged , Asian People , Cross-Sectional Studies , Female , Health Status , Humans , Kidney Failure, Chronic/therapy , Male , Middle Aged , Singapore
6.
Diabetes Metab ; 41(4): 291-300, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25575429

ABSTRACT

AIM: The study investigated the relationship of general (body mass index [BMI]) and central (waist circumference [WC]; waist-hip ratio [WHipR]; waist-height ratio [WHeightR]) adiposity with all-cause and cardiovascular disease (CVD)-related mortality in an Asian population with diabetes. METHODS: A total of 13,278 participants with type 2 diabetes mellitus (T2DM) recruited from public-sector primary-care and specialist outpatients clinics in Singapore were followed-up for a median duration of 2.9 years, during which time there were 524 deaths. Cox proportional-hazards regression and competing-risk models were used to obtain hazard ratios (HRs) for anthropometric variables of all-cause and CVD-related mortality. RESULTS: After adjusting for BMI, the highest quintiles of WC, WHipR and WHeightR were all positively associated with mortality compared with the lowest quintiles, with WHeightR exhibiting the largest effect sizes [all-cause mortality HR: 2.13, 95% confidence interval (CI): 1.33-3.42; CVD-related mortality HR: 3.42, 95% CI: 1.62-7.19]. Being overweight but not obese (BMI:≥23.0 but<27.5kg/m(2)) was associated with a decreased risk of CVD-related mortality in those aged≥65 years (HR: 0.47, 95% CI: 0.29-0.75), but not in those aged<65 years (HR: 1.11, 95% CI: 0.49-2.50). CONCLUSION: Overweight, but not obesity, was associated with a reduction in risk of mortality. This was seen in T2DM patients aged≥65 years, but not in those younger than this. At the same BMI, having higher central-obesity indices such as WC, WHipR and WHeightR also increased the risk of mortality.


Subject(s)
Body Weights and Measures , Cardiovascular Diseases/mortality , Diabetes Mellitus, Type 2/mortality , Obesity/mortality , Adiposity/ethnology , Aged , Asian People/statistics & numerical data , Body Mass Index , Body Weights and Measures/standards , Body Weights and Measures/statistics & numerical data , Cardiovascular Diseases/complications , Cause of Death , Cohort Studies , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/ethnology , Diabetes Mellitus, Type 2/metabolism , Female , Health Status Indicators , Humans , Male , Middle Aged , Obesity/complications , Obesity/ethnology , Obesity/metabolism , Risk Factors , Singapore/epidemiology , Waist Circumference/ethnology , Waist-Hip Ratio/statistics & numerical data
7.
Pharmacogenomics J ; 14(6): 555-63, 2014 Dec.
Article in English | MEDLINE | ID: mdl-24861855

ABSTRACT

Differences in the frequency of pharmacogenomic variants may influence inter-population variability in drug efficacy and risk of adverse drug reactions (ADRs). We investigated the diversity of ∼ 4500 genetic variants in key drug-biotransformation and -response genes among three South East Asian populations compared with individuals of European ancestry. We compared rates of reported ADRs in these Asian populations to determine if the allelic differentiation corresponded to an excess of the associated ADR. We identified an excess of ADRs related to clopidogrel in Singaporean Chinese, consistent with a higher frequency of a known risk variant in CYP2C19 in that population. We also observed an excess of ADRs related to platinum compounds in Singaporean CHS, despite a very low frequency of known ADR risk variants, suggesting the presence of additional genetic and non-genetic risk factors. Our results point to substantial diversity at specific pharmacogenomic loci that may contribute to inter-population variability in drug response phenotypes.


Subject(s)
Drug-Related Side Effects and Adverse Reactions , Genetic Variation/genetics , Biotransformation , Europe , Humans , Singapore
10.
Br J Cancer ; 109(8): 2035-43, 2013 Oct 15.
Article in English | MEDLINE | ID: mdl-24084766

ABSTRACT

BACKGROUND: Natural history models of breast cancer progression provide an opportunity to evaluate and identify optimal screening scenarios. This paper describes a detailed Markov model characterising breast cancer tumour progression. METHODS: Breast cancer is modelled by a 13-state continuous-time Markov model. The model differentiates between indolent and aggressive ductal carcinomas in situ tumours, and aggressive tumours of different sizes. We compared such aggressive cancers, that is, which are non-indolent, to those which are non-growing and regressing. Model input parameters and structure were informed by the 1978-1984 Ostergotland county breast screening randomised controlled trial. Overlaid on the natural history model is the effect of screening on diagnosis. Parameters were estimated using Bayesian methods. Markov chain Monte Carlo integration was used to sample the resulting posterior distribution. RESULTS: The breast cancer incidence rate in the Ostergotland population was 21 (95% CI: 17-25) per 10 000 woman-years. Accounting for length-biased sampling, an estimated 91% (95% CI: 85-97%) of breast cancers were aggressive. Larger tumours, 21-50 mm, had an average sojourn of 6 years (95% CI: 3-16 years), whereas aggressive ductal carcinomas in situ took around half a month (95% CI: 0-1 month) to progress to the invasive ≤10 mm state. CONCLUSION: These tumour progression rate estimates may facilitate future work analysing cost-effectiveness and quality-adjusted life years for various screening strategies.


Subject(s)
Breast Neoplasms/pathology , Models, Biological , Adult , Aged , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/epidemiology , Carcinoma in Situ/diagnostic imaging , Carcinoma in Situ/epidemiology , Carcinoma in Situ/pathology , Carcinoma, Ductal, Breast/diagnostic imaging , Carcinoma, Ductal, Breast/epidemiology , Carcinoma, Ductal, Breast/pathology , Disease Progression , Early Detection of Cancer/methods , Early Detection of Cancer/statistics & numerical data , Female , Humans , Mammography , Markov Chains , Middle Aged , Monte Carlo Method , Randomized Controlled Trials as Topic , Reproducibility of Results , Sweden/epidemiology
11.
Pharmacogenomics J ; 12(4): 312-8, 2012 Aug.
Article in English | MEDLINE | ID: mdl-21383771

ABSTRACT

Genetic markers displaying highly significant statistical associations with complex phenotypes may not necessarily possess sufficient clinical validity to be useful. Understanding the contribution of these markers beyond readily available clinical biomarkers is particularly important in pharmacogenetics. We demonstrate the utility of genetic testing using the example of warfarin in a multi-ethnic setting comprising of three Asian populations that are broadly representative of the genetic diversity for half of the population in the world, especially as distinct interethnic differences in warfarin dose requirements have been previously established. We confirmed the roles of three well-established loci (CYP2C9, VKORC1 and CYP4F2) in explaining warfarin dosage variation in the three Asian populations. In addition, we assessed the relationship between ethnicity and the genotypes of these loci, observing strong correlations at VKORC1 and CYP4F2. Subsequently, we established the additional utility of these genetic factors in predicting warfarin dose beyond ethnicity and clinical biomarkers through performing a series of systematic cross-validation analyses of the relative predictive accuracies of various fixed-dose regimen, clinical and genetic models. Through a pharmacogenetics model for warfarin, we show the importance of genetic testing beyond readily available clinical biomarkers in predicting dose requirements, confirming the role of genetic profiling in personalized medicine.


Subject(s)
Cytochrome P-450 Enzyme System/genetics , Mixed Function Oxygenases/genetics , Pharmacogenetics/methods , Aryl Hydrocarbon Hydroxylases/genetics , Asian People/genetics , China/ethnology , Cytochrome P450 Family 4 , Ethnicity/genetics , Humans , India/ethnology , Malaysia/ethnology , Polymorphism, Genetic , Precision Medicine/trends , Singapore , Vitamin K Epoxide Reductases , Warfarin/administration & dosage
12.
IARC Sci Publ ; (162): 183-98, 2011.
Article in English | MEDLINE | ID: mdl-21675423

ABSTRACT

The Singapore cancer registry is a national registry established in 1968. Cancer registration is done by passive methods. The registry contributed survival data on 45 cancer sites or types registered during 1993-1997. Data on 34 cancers registered during 1968-1997 were utilized for survival trend by period and cohort approaches. Follow-up was done by passive methods, with median follow-up ranging between 2-72 months for different cancers. The proportion with histologically verified diagnosis for various cancers ranged between 27-100%; death certificates only (DCOs) comprised 0-7%; 76-100% of total registered cases were included for the survival analysis. The top-ranking cancers on 5-year age-standardized relative survival rates were nonmelanoma skin (96%), thyroid (90%), testis (88%), corpus uteri (77%), breast (74%), Hodgkin lymphoma (73%) and penis (70%). Five-year relative survival by age group showed either a decreasing trend with increasing age groups or was fluctuating. Localized stage of disease ranged between 18-65% for various cancers and survival decreased with increasing extent of disease. Period survival closely predicted survival experience of cancers diagnosed in that period, and an increasing trend in period survival over different periods indicated an improved prognosis for cancers diagnosed in those calendar periods.


Subject(s)
Neoplasms/mortality , Adolescent , Adult , Aged , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Male , Middle Aged , Registries , Singapore , Time Factors
14.
Br J Cancer ; 104(5): 871-4, 2011 Mar 01.
Article in English | MEDLINE | ID: mdl-21245860

ABSTRACT

BACKGROUND: Joint effects of mammographic density and other risk factors on breast cancer risk remain unclear. METHODS: From The Singapore Breast Screening Project, we selected 491 cases and 982 controls. Mammographic density was measured quantitatively. Data analysis was by conditional logistic regression. RESULTS: Density was a significant risk factor, adjusting for other factors. Density of 76-100% had an odds ratio of 5.54 (95% CI 2.38-12.90) compared with 0-10%. Density had significant interactions with body mass index and oral contraceptive use (P=0.02). CONCLUSIONS: Percent density increases breast cancer risk in addition to effects of other risk factors, and modifies the effects of BMI and OCs.


Subject(s)
Breast Neoplasms/diagnostic imaging , Mammography , Aged , Asian People , Body Mass Index , Breast Neoplasms/pathology , Humans , Middle Aged , Risk Factors , Singapore
15.
Singapore Med J ; 51(7): 536-41, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20730392

ABSTRACT

Over the past decade, global health has evolved from a buzzword to a discipline, attracting interest from governments, academic institutions and funding organisations. Global health centres, institutes and initiatives in Western countries have increased in both size and number, aided primarily by institutional backing and supportive funding mechanisms. As the rise to prominence of global health on the public health agenda also coincides with shifts in global balances of power, Asia, as well as Singapore, has an expanded role to play in supporting global health teaching and research, both in the region and throughout the world. Foundations, universities, government agencies, statutory boards and the private sector all have an important role to play in moving the global health agenda forward in Singapore. Rigorous global health training and increased funding for global health research are now timely and essential in order for global health, as a discipline, to develop within Singapore and have an impact within the region.


Subject(s)
Global Health , Public Health , Developing Countries , Female , Forecasting , Humans , Male , Needs Assessment , Organizational Innovation , Singapore , Socioeconomic Factors , Tropical Medicine/organization & administration , World Health Organization/economics
16.
Br J Surg ; 97(8): 1253-9, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20602496

ABSTRACT

BACKGROUND: This study quantified long-term absolute and relative mortality risks of survivors of breast cancer with subsequent childbirth. METHODS: The Singapore Birth Register (n = 319,437), Swedish Multi-Generation Register (n = 11 million) and population-based cancer registries were linked to identify 492 women with childbirth after breast cancer. For these women, cumulative mortality risks and standardized mortality ratios (SMRs) were calculated and compared with those of 8529 women aged less than 40 years with breast cancer without subsequent childbirth, and with those predicted by Adjuvant! Online. RESULTS: Women with subsequent childbirth had a lower 15-year cumulative overall mortality rate than other women with breast cancer (16.8 (95 per cent confidence interval (c.i.) 13.3 to 20.9) versus 40.7 (39.5 to 41.9) per cent), but a higher relative mortality risk than the background population (SMR 13.6, 95 per cent c.i. 10.6 to 17.3). Mortality risks decreased significantly with increasing interval between diagnosis and subsequent childbirth. Mean 10-year cumulative mortality risks of women with subsequent childbirth were within the range of 10-year mortality predicted by Adjuvant! Online for women with T1 N0 tumours in otherwise perfect health. CONCLUSION: This study reinforced the view that pregnancy after breast cancer is not detrimental to survival. However, women who gave birth after this diagnosis had substantially higher mortality risks than young women in the general population. This information may be a valuable addition to routine mortality estimates.


Subject(s)
Breast Neoplasms/mortality , Pregnancy Complications, Neoplastic/mortality , Survivors/statistics & numerical data , Adolescent , Adult , Breast Neoplasms/therapy , Child , Female , Humans , Pregnancy , Registries , Risk Factors , Singapore/epidemiology , Survival Rate , Sweden/epidemiology , Young Adult
17.
Br J Cancer ; 102(7): 1190-5, 2010 Mar 30.
Article in English | MEDLINE | ID: mdl-20354532

ABSTRACT

BACKGROUND: Patterns of second primary cancers (SPCs) following first primary lung cancers (FPLCs) may provide aetiological insights into FPLC. METHODS: Cases of FPLCs in 13 cancer registries in Europe, Australia, Canada, and Singapore were followed up from the date of FPLC diagnosis to the date of SPC diagnosis, date of death, or end of follow-up. Standardised incidence ratios (SIRs) were calculated to estimate the magnitude of SPC development following squamous cell carcinoma (SCC), small cell lung carcinoma (SCLC), and adenocarcinoma (ADC). RESULTS: Among SCC patients, male SIR=1.58 (95% confidence interval (CI)=1.50-1.66) and female SIR=2.31 (1.94-2.72) for smoking-related SPC. Among SCLC patients, the respective ratios were 1.39 (1.20-1.60) and 2.28 (1.73-2.95), and among ADC patients, they were 1.73 (1.57-1.90) and 2.24 (1.91-2.61). We also observed associations between first primary lung ADC and second primary breast cancer in women (SIR=1.25, 95% CI=1.05-1.48) and prostate cancer (1.56, 1.39-1.79) in men. CONCLUSION: The FPLC patients carried excess risks of smoking-related SPCs. An association between first primary lung ADC and second primary breast and ovarian cancer in women at younger age and prostate cancers in men may reflect an aetiological role of hormones in lung ADC.


Subject(s)
Lung Neoplasms/epidemiology , Neoplasms, Second Primary/etiology , Adenocarcinoma/epidemiology , Aged , Carcinoma, Squamous Cell/epidemiology , Female , Humans , Incidence , Male , Middle Aged , Neoplasms, Second Primary/epidemiology , Risk Factors , Small Cell Lung Carcinoma/epidemiology
18.
Neurology ; 73(22): 1866-72, 2009 Dec 01.
Article in English | MEDLINE | ID: mdl-19949033

ABSTRACT

BACKGROUND: The utility of poststroke cognitive status, namely dementia, cognitive impairment no dementia (CIND), mild cognitive impairment (MCI), and no cognitive impairment (NCI), in predicting dementia has been previously examined. However, no studies to date have compared the ability of subtypes of MCI and CIND to predict dementia in a poststroke population. METHODS: A cohort of ischemic stroke patients underwent neuropsychological assessment annually for up to 5 years. Dementia was defined using the DSM-IV criteria. Univariate and multivariable Cox proportional regression was performed to determine the ability of MCI subtypes, CIND severity, and individual domains of impairment to predict dementia. RESULTS: A total of 362 patients without dementia were followed up for a mean of 3.4 years (17% drop out), with 24 developing incident dementia. Older age, previous and recurrent stroke, and CIND and MCI subtypes were significant predictors of dementia. In multivariable analysis controlling for treatment allocation, patients who were older, had previous or recurrent stroke, and had either CIND moderate or multiple domain MCI with amnestic component were at elevated risk for dementia. In multivariable domain analysis, recurrent strokes, age, and previous strokes, verbal memory, and visual memory were significant predictors of dementia. Receiver operating characteristic curve analysis showed that CIND moderate (area under the curve: 0.893) and multiple domain MCI with amnestic component (area under the curve: 0.832) were significant predictors of conversion to dementia. All other classifications of cognitive impairment had areas under the curve less than 0.7. CONCLUSION: Stroke patients with cognitive impairment no dementia (CIND) moderate are at higher risk of developing dementia, while CIND mild patients are not at increased risk of developing dementia.


Subject(s)
Cognition Disorders/epidemiology , Dementia/epidemiology , Stroke/epidemiology , Aged , Analysis of Variance , Cognition Disorders/etiology , Cohort Studies , Dementia/etiology , Diagnostic and Statistical Manual of Mental Disorders , Disease Progression , Female , Humans , Incidence , Male , Middle Aged , Neuropsychological Tests , Predictive Value of Tests , Proportional Hazards Models , ROC Curve , Retrospective Studies , Risk Factors , Severity of Illness Index , Stroke/complications
19.
Diabetologia ; 52(7): 1343-51, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19415232

ABSTRACT

AIMS/HYPOTHESIS: Evolving research suggests that common and rare alleles jointly constitute the genetic landscape of complex disease. We studied the association between 43 pathway-related candidate genes with 'intermediate phenotype' (i.e. corresponding plasma protein) and diabetic nephropathy in a customised microarray of 1,536 SNPs. METHODS: In this case-control study of type 2 diabetic Chinese individuals with and without diabetic nephropathy, cases (n = 545) were defined on the basis of a spot urinary albumin/creatinine ratio (ACR) > 113 mg/mmol; the value for controls (n = 503) was ACR < 3.3 mg/mmol. Genotyping was performed using Illumina GoldenGate assay. RESULTS: No single nucleotide polymorphism (SNP) remained significant in single locus analysis after correction for multiple testing. Therefore, we explored the best approximately 1% SNPs. Of these 13 SNPs, four clustered to a 5' end NADPH oxidase homologue 4 (NOX4) haplotype (GGCC frequency = 0.776) with estimated OR for diabetic nephropathy of 2.05 (95% CI 1.04-4.06) (heterozygous) and 2.48 (1.27-4.83) (homozygous) (p = 0.0055). The haplotype was correlated with plasma Cu/Zn superoxide dismutase (SOD) concentration, suggesting increased oxidative burden. Endothelin-1 SNP (rs1476046G>A, frequency = 0.252) was correlated with plasma C-terminal pro-endothelin-1 concentrations with an estimated OR for diabetic nephropathy of (heterozygous) 1.26 (0.96-1.66) and (homozygous) 1.87 (1.13-3.12) (p = 0.0072). Nitric oxide synthase 1 (NOS1) 5' haplotype (TGTC frequency = 0.38) also revealed a suggestive association with diabetic nephropathy: heterozygous 1.26 (0.95-1.67), homozygous 1.57 (1.04-2.35) (p = 0.0073). A rare NADPH oxidase homologue 1 (NOX1)-coding non-synonymous SNP (Arg315His, frequency = 0.006) was found exclusively among cases. CONCLUSIONS/INTERPRETATION: Our preliminary observations suggest that common haplotypes from NOX4 and endothelin-1 SNP correlated with plasma Cu/Zn SOD and C-terminal pro-endothelin-1 concentrations, respectively, and might have conferred diabetic nephropathy susceptibility. Common NOS1 and rare NOX1 variants also revealed a suggestive association with diabetic nephropathy. Future studies to validate our observation are needed.


Subject(s)
Asian People/genetics , Diabetes Mellitus, Type 2/genetics , Diabetic Nephropathies/genetics , Endothelin-1/genetics , NADPH Oxidases/genetics , Nitric Oxide Synthase Type I/genetics , Aged , Blood Proteins/genetics , Case-Control Studies , Diabetes Mellitus, Type 2/ethnology , Diabetic Nephropathies/ethnology , Female , Genetic Predisposition to Disease/ethnology , Haplotypes , Humans , Male , Middle Aged , NADPH Oxidase 4 , Oligonucleotide Array Sequence Analysis , Polymorphism, Single Nucleotide , Singapore/epidemiology
20.
Eur J Cancer ; 44(6): 830-9, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18329873

ABSTRACT

PURPOSE: The aim of this study was to assess the risk of second malignant neoplasms (SMNs) other than central nervous system (CNS) neoplasms after childhood CNS cancer in an international multicentre study. METHODS: Individual data on cases of CNS cancer in children (0-14 years) and on subsequent SMNs were obtained from 13 population-based cancer registries contributing data for different time periods in 1943-2000. Standardised incidence ratios (SIRs) with 95% confidence intervals (CI), absolute excess risk and cumulative incidence of SMNs were computed. RESULTS: We observed 43 SMNs in 8431 CNS cancer survivors. The SIR was 10.6 (4.85-20.1) for thyroid cancer (nine cases), 2.75 (1.01-5.99) for leukaemia (six cases) and 2.47 (0.90-5.37) for lymphoma (six cases). The SIRs were highest in the first 10 years after CNS cancer diagnosis. The cumulative incidence of non-CNS SMNs was 3.30% (0.95-5.65%) within 45 years after a CNS cancer diagnosis. Within 15 years, the cumulative incidence was highest for cases diagnosed after 1980 (0.56%, 95% CI: 0.29-0.82%). CONCLUSION: This population-based study indicates that about one every 180 survivors of a childhood CNS cancer will develop a non-CNS SMN within the following 15 years. The excess is higher after glioma and embryonal malignant tumour than after another CNS tumour.


Subject(s)
Central Nervous System Neoplasms/epidemiology , Neoplasms, Second Primary/epidemiology , Adolescent , Adult , Aged , Child , Child, Preschool , Epidemiologic Methods , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Risk
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