METHODS: This is a retrospective analysis of the Malaysian National Cardiovascular Disease Database-Acute Coronary Syndrome registry from year 2006 to 2013 (n = 30,873). On-discharge pharmacotherapies examined were aspirin, ADP-antagonists, statins, ACE-inhibitors, angiotensin-II-receptor blockers, and beta-blockers. Multivariate logistic regression was used to calculate adjusted odds ratio of receiving individual pharmacotherapies according to patients' characteristics in NSTEMI patients (n = 11,390).
RESULTS: Prescribing rates for cardiovascular pharmacotherapies had significantly increased especially for ADP-antagonists (76%) in NSTEMI patients. More than 85% were prescribed statins and antiplatelets but rates remained significantly lower compared to STEMI. Women and those over 65 years old were less likely to be prescribed these pharmacotherapies compared to men and younger NSTEMI patients. Chinese and Indians were more likely to receive selected pharmacotherapies compared to Malays (main ethnicity). Geographical variations were observed; East Malaysian (Malaysian Borneo) patients were less likely to receive these compared to Western region of Malaysian Peninsular. Underprescribing in patients with risk factors such as diabetes were observed with other co-morbidities influencing prescribing selectively.
CONCLUSION: This study uncovers demographic and clinical variations in cardiovascular pharmacotherapies prescribing for NSTEMI. Concerted efforts by policy makers, specialty societies, and physicians are required focusing on elderly, women, Malays, East Malaysians, and high-risk patients.
OBJECTIVE: Apply machine learning for the prediction and identification of factors associated with short and long-term mortality in Asian STEMI patients and compare with a conventional risk score.
METHODS: The National Cardiovascular Disease Database for Malaysia registry, of a multi-ethnic, heterogeneous Asian population was used for in-hospital (6299 patients), 30-days (3130 patients), and 1-year (2939 patients) model development. 50 variables were considered. Mortality prediction was analysed using feature selection methods with machine learning algorithms and compared to Thrombolysis in Myocardial Infarction (TIMI) score. Invasive management of varying degrees was selected as important variables that improved mortality prediction.
RESULTS: Model performance using a complete and reduced variable produced an area under the receiver operating characteristic curve (AUC) from 0.73 to 0.90. The best machine learning model for in-hospital, 30 days, and 1-year outperformed TIMI risk score (AUC = 0.88, 95% CI: 0.846-0.910; vs AUC = 0.81, 95% CI:0.772-0.845, AUC = 0.90, 95% CI: 0.870-0.935; vs AUC = 0.80, 95% CI: 0.746-0.838, AUC = 0.84, 95% CI: 0.798-0.872; vs AUC = 0.76, 95% CI: 0.715-0.802, p < 0.0001 for all). TIMI score underestimates patients' risk of mortality. 90% of non-survival patients are classified as high risk (>50%) by machine learning algorithm compared to 10-30% non-survival patients by TIMI. Common predictors identified for short- and long-term mortality were age, heart rate, Killip class, fasting blood glucose, prior primary PCI or pharmaco-invasive therapy and diuretics. The final algorithm was converted into an online tool with a database for continuous data archiving for algorithm validation.
CONCLUSIONS: In a multi-ethnic population, patients with STEMI were better classified using the machine learning method compared to TIMI scoring. Machine learning allows for the identification of distinct factors in individual Asian populations for better mortality prediction. Ongoing continuous testing and validation will allow for better risk stratification and potentially alter management and outcomes in the future.
METHODS: We used robust statistical methods including the Cause of Death Ensemble model (CODEm) to analyse a database of data for 7065 site-years and estimate the number of maternal deaths from all causes in 188 countries between 1990 and 2013. We estimated the number of pregnancy-related deaths caused by HIV on the basis of a systematic review of the relative risk of dying during pregnancy for HIV-positive women compared with HIV-negative women. We also estimated the fraction of these deaths aggravated by pregnancy on the basis of a systematic review. To estimate the numbers of maternal deaths due to nine different causes, we identified 61 sources from a systematic review and 943 site-years of vital registration data. We also did a systematic review of reports about the timing of maternal death, identifying 142 sources to use in our analysis. We developed estimates for each country for 1990-2013 using Bayesian meta-regression. We estimated 95% uncertainty intervals (UIs) for all values.
FINDINGS: 292,982 (95% UI 261,017-327,792) maternal deaths occurred in 2013, compared with 376,034 (343,483-407,574) in 1990. The global annual rate of change in the MMR was -0·3% (-1·1 to 0·6) from 1990 to 2003, and -2·7% (-3·9 to -1·5) from 2003 to 2013, with evidence of continued acceleration. MMRs reduced consistently in south, east, and southeast Asia between 1990 and 2013, but maternal deaths increased in much of sub-Saharan Africa during the 1990s. 2070 (1290-2866) maternal deaths were related to HIV in 2013, 0·4% (0·2-0·6) of the global total. MMR was highest in the oldest age groups in both 1990 and 2013. In 2013, most deaths occurred intrapartum or postpartum. Causes varied by region and between 1990 and 2013. We recorded substantial variation in the MMR by country in 2013, from 956·8 (685·1-1262·8) in South Sudan to 2·4 (1·6-3·6) in Iceland.
INTERPRETATION: Global rates of change suggest that only 16 countries will achieve the MDG 5 target by 2015. Accelerated reductions since the Millennium Declaration in 2000 coincide with increased development assistance for maternal, newborn, and child health. Setting of targets and associated interventions for after 2015 will need careful consideration of regions that are making slow progress, such as west and central Africa.
FUNDING: Bill & Melinda Gates Foundation.
METHODS: In 14 Central England general practices, a novel case-finding tool (Familial Hypercholetserolaemia Case Ascertainment Tool, FAMCAT1) was applied to the electronic health records of 86 219 patients with cholesterol readings (44.5% of total practices' population), identifying 3375 at increased risk of FH. Of these, a cohort of 336 consenting to completing Family History Questionnaire and detailed review of their clinical data, were offered FH genetic testing in primary care.
RESULTS: Genetic testing was completed by 283 patients, newly identifying 16 with genetically confirmed FH and 10 with variants of unknown significance. All 26 (9%) were recommended for referral and 19 attended specialist assessment. In a further 153 (54%) patients, the test suggested polygenic hypercholesterolaemia who were managed in primary care. Total cholesterol and low-density lipoprotein-cholesterol levels were higher in those patients with FH-causing variants than those with other genetic test results (p=0.010 and p=0.002).
CONCLUSION: Electronic case-finding and genetic testing in primary care could improve identification of FH; and the better targeting of patients for specialist assessment. A significant proportion of patients identified at risk of FH are likely to have polygenic hypercholesterolaemia. There needs to be a clearer management plan for these individuals in primary care.
TRIAL REGISTRATION NUMBER: NCT03934320.
OBJECTIVES: To determine the prevalence and descriptive epidemiology of atopic dermatitis among school children in the general community in Singapore.
METHODS: This is a questionnaire study of 12 323 students done over a 1-year period, comprising 7 year olds (4605), 12 year olds (3940) and 16 year olds (3778) from 19 primary and 17 secondary schools randomly selected in Singapore. All children had a complete cutaneous examination. The diagnosis of atopic dermatitis was based on the U.K. Working Party diagnostic criteria. The questionnaire was translated into Chinese and both the English and Chinese versions were issued simultaneously to the students.
RESULTS: The 1-year period prevalence of atopic dermatitis was 20.8%. Atopic dermatitis was present in 22.7% of 7 year olds, 17.9% of 12 year olds and 21.5% of 16 year olds. The overall sex ratio was equal. There were slightly more boys with atopic dermatitis among the younger children (6 and 12 year olds, 1.18 : 1 and 1.19 : 1, respectively) but more girls were affected (1.57 : 1) among the 16 year olds. Atopic dermatitis was more common among the Chinese (21.6%) and Malays (19.8%) compared with the Indians (16%) and other races (14%). The onset of the disease occurred before the age of 10 years in 49.5% of the 16 year olds. "Pure" atopic dermatitis without concomitant respiratory allergies was noted in 788 respondents (30.7%); 1775 (69.3%) suffered from a "mixed" type, with 34.3% having allergic rhinitis, 9.5% having asthma and 25.5% having both asthma and allergic rhinitis. More boys had atopic dermatitis and concomitant respiratory allergies whereas more girls were affected with "pure" atopic dermatitis alone (1.4 : 1). At least one first-degree family member with atopy was noted in 1435 children (56%): atopic dermatitis (70%), asthma (62%) and allergic rhinitis (68%). Among siblings with one parent with atopic dermatitis, 37% had either a father or a mother with atopic dermatitis. Common aggravating factors reported included exercise, heat and sweating, grass intolerance, thick clothing and stress. Pityriasis alba was noted in 25% of the study population, keratosis pilaris in 13% and ichthyosis vulgaris in 8%. Most respondents had mild to moderate atopic dermatitis that could be controlled with a fairly simple regimen of moisturizers, topical steroids, antihistamines and antibiotics.
CONCLUSIONS: The high prevalence of atopic dermatitis in Singapore is similar to that observed in developed countries, suggesting that environmental factors may be important in determining the expression of the disease.
Objectives: To identify novel genome-wide significant loci for PD in Asian individuals and to compare genetic risk between Asian and European cohorts.
Design Setting, and Participants: Genome-wide association data generated from PD cases and controls in an Asian population (ie, Singapore/Malaysia, Hong Kong, Taiwan, mainland China, and South Korea) were collected from January 1, 2016, to December 31, 2018, as part of an ongoing study. Results were combined with inverse variance meta-analysis, and replication of top loci in European and Japanese samples was performed. Discovery samples of 31 575 individuals passing quality control of 35 994 recruited were used, with a greater than 90% participation rate. A replication cohort of 1 926 361 European-ancestry and 3509 Japanese samples was analyzed. Parkinson disease was diagnosed using UK Parkinson's Disease Society Brain Bank Criteria.
Main Outcomes and Measures: Genotypes of common variants, association with disease status, and polygenic risk scores.
Results: Of 31 575 samples identified, 6724 PD cases (mean [SD] age, 64.3 [10] years; age at onset, 58.8 [10.6] years; 3472 [53.2%] men) and 24 851 controls (age, 59.4 [11.4] years; 11 030 [45.0%] men) were analyzed in the discovery study. Eleven genome-wide significant loci were identified; 2 of these loci were novel (SV2C and WBSCR17) and 9 were previously found in Europeans. Replication in European-ancestry and Japanese samples showed robust association for SV2C (rs246814; odds ratio, 1.16; 95% CI, 1.11-1.21; P = 1.17 × 10-10 in meta-analysis of discovery and replication samples) but showed potential genetic heterogeneity at WBSCR17 (rs9638616; I2=67.1%; P = 3.40 × 10-3 for hetereogeneity). Polygenic risk score models including variants at these 11 loci were associated with a significant improvement in area under the curve over the model based on 78 European loci alone (63.1% vs 60.2%; P = 6.81 × 10-12).
Conclusions and Relevance: This study identified 2 apparently novel gene loci and found 9 previously identified European loci to be associated with PD in this large, meta-genome-wide association study in a worldwide population of Asian individuals and reports similarities and differences in genetic risk factors between Asian and European individuals in the risk for PD. These findings may lead to improved stratification of Asian patients and controls based on polygenic risk scores. Our findings have potential academic and clinical importance for risk stratification and precision medicine in Asia.
Objective: To identify any associations between depressive symptoms and incident CVD and all-cause mortality in countries at different levels of economic development and in urban and rural areas.
Design, Setting, and Participants: This multicenter, population-based cohort study was conducted between January 2005 and June 2019 (median follow-up, 9.3 years) and included 370 urban and 314 rural communities from 21 economically diverse countries on 5 continents. Eligible participants aged 35 to 70 years were enrolled. Analysis began February 2018 and ended September 2019.
Exposures: Four or more self-reported depressive symptoms from the Short-Form Composite International Diagnostic Interview.
Main Outcomes and Measures: Incident CVD, all-cause mortality, and a combined measure of either incident CVD or all-cause mortality.
Results: Of 145 862 participants, 61 235 (58%) were male and the mean (SD) age was 50.05 (9.7) years. Of those, 15 983 (11%) reported 4 or more depressive symptoms at baseline. Depression was associated with incident CVD (hazard ratio [HR], 1.14; 95% CI, 1.05-1.24), all-cause mortality (HR, 1.17; 95% CI, 1.11-1.25), the combined CVD/mortality outcome (HR, 1.18; 95% CI, 1.11-1.24), myocardial infarction (HR, 1.23; 95% CI, 1.10-1.37), and noncardiovascular death (HR, 1.21; 95% CI, 1.13-1.31) in multivariable models. The risk of the combined outcome increased progressively with number of symptoms, being highest in those with 7 symptoms (HR, 1.24; 95% CI, 1.12-1.37) and lowest with 1 symptom (HR, 1.05; 95% CI, 0.92 -1.19; P for trend risk of incident CVD and mortality in economically diverse settings, especially in urban areas. Improving understanding and awareness of these physical health risks should be prioritized as part of a comprehensive strategy to reduce the burden of noncommunicable diseases worldwide.