METHODS: Warfarin relies on regular monitoring of International Normalized Ratio which is a standardized test to measure prothrombin time and appropriate dose adjustment. Pharmacometabonomics is a novel scientific field which deals with identification and quantification of the metabolites present in the metabolome using spectroscopic techniques such as Nuclear Magnetic Resonance (NMR). Pharmacometabonomics helps to indicate perturbation in the levels of metabolites in the cells and tissues due to drug or ingestion of any substance. NMR is one of the most widely-used spectroscopic techniques in metabolomics because of its reproducibility and speed.
RESULTS: There are many factors that influence the metabolism of warfarin, making changes in drug dosage common, and clinical factors like drug-drug interactions, dietary interactions and age explain for the most part the variability in warfarin dosing. Some studies have showed that pharmacogenetic testing for warfarin dosing does not improve health outcomes, and around 26% of the variation in warfarin dose requirements remains unexplained yet.
CONCLUSION: Many recent pharmacometabonomics studies have been conducted to identify novel biomarkers of drug therapies such as paracetamol, aspirin and simvastatin. Thus, a technique such as NMR based pharmacometabonomics to find novel biomarkers in plasma and urine might be useful to predict warfarin outcome.
PURPOSE: The aim was to determine the metabolic fingerprint that predicts warfarin response based on the international normalized ratio (INR) in patients who are already receiving warfarin (phase I: identification) and to ascertain the metabolic fingerprint that discriminates stable from unstable INR in patients starting treatment with warfarin (phase II: validation).
EXPERIMENTAL APPROACH: A total of 94 blood samples were collected for phase I: 44 patients with stable INR and 50 with unstable INR. Meanwhile, 23 samples were collected for phase II: nine patients with stable INR and 14 with unstable INR. Data analysis was performed using multivariate analysis including principal component analysis and partial least square-discriminate analysis (PLS-DA), followed by univariate and multivariate logistic regression (MVLR) to develop a model to identify unstable INR biomarkers.
KEY RESULTS: For phase I, the PLS-DA model showed the following results: sensitivity 93.18%, specificity 91.49% and accuracy 92.31%. In the MVLR analysis of phase I, ten regions were associated with unstable INR. For phase II, the PLS-DA model showed the following results: sensitivity 66.67%, specificity 61.54% and accuracy 63.64%.
CONCLUSIONS AND IMPLICATIONS: We have shown that the pharmacometabonomics technique was able to differentiate between unstable and stable INR with good accuracy. NMR-based pharmacometabonomics has the potential to identify novel biomarkers in plasma, which can be useful in individualizing treatment and controlling warfarin side effects, thus, minimizing undesirable effects in the future.
DESIGN: Cross-sectional study.
SETTING: Primary and secondary schools in Malaysia.
PARTICIPANTS: 11 246 non-smoking school-going adolescents.
OUTCOME MEASURES: The prevalence and factors associated with smoking susceptibility among non-smoking school-going adolescents in Malaysia.
RESULTS: Approximately 14% of non-smokers were susceptible to smoking, and the prevalence of susceptibility was significantly higher among males, ever-smokers and e-cigarette users. The odds of susceptibility to smoking were higher among males, e-cigarette users, those aged 12 years and under and those who had ever smoked or tried cigarettes. Students from schools with educational programmes on the health effects of second-hand smoke (SHS) and who perceived smoking to be harmful were less likely to be susceptible to smoking.
CONCLUSION: Smoking susceptibility is prevalent among school-going adolescents. A comprehensive approach that enhances or reinforces health education programmes on the adverse health effects of smoking and SHS among school children, that considers multiple factors and that involves all stakeholders is urgently needed to reduce the prevalence of smoking susceptibility among vulnerable subgroups, as identified from the present findings.
METHODS: The data were derived from the Malaysian Global Adult Tobacco Survey (GATS-M), collected in 2011-2012, involving 4250 respondents. Data analyses involved 1343 respondents reported to be in the working population.
RESULTS: More than half of the respondents (58.5%) were reportedly working in smoke-free workplaces. Almost a quarter (24.8%) of those who worked in smoke-free workplaces stayed in smoke-free homes, which was more than two times higher than their counterparts who worked at non-smoke-free workplaces (24.8% vs 12.0%, p<0.001). Multivariable analyses further substantiated this finding (AOR=2.01, 95% CI: 1.11-3.61, reference group = worked at non-smoke-free workplaces).
CONCLUSIONS: This study found an association between living in smoke-free homes and working at smoke-free workplaces, which could suggest a positive impact of implementing smoke-free workplaces.
METHODS: A self-administered validated questionnaire was used to obtain data from the nationally representative samples of school-going adolescents aged 11-19 years in Malaysia. Prevalence rates were computed and chi-squared tests and multiple logistic regression were conducted.
RESULTS: Of the participants, 23.3% reported exposure to SHS at least once in the car of their parents/guardians during the last 7 days before the survey. The prevalence and likelihood of SHS exposure were significantly higher in Malays, descendants of natives of Sabah and Sarawak, schools in rural areas, females, and current smokers. However, age group and knowledge on the harmful effects of SHS were not significant after adjusting for confounding effects.
CONCLUSIONS: A substantial proportion of school-going adolescents were exposed to secondhand smoke in the car of their parents/guardians. This highlights the need for effective tobacco control measures to include health promotion and smoke-free car regulations to be introduced to prevent severe health hazards and to reduce smoking initiation among non-smoking adolescents.
METHODS: Pre-dosed urine samples were collected from male Sprague-Dawley rats. The rats were treated with either LDA (10 mg/kg) or 1% methylcellulose (10 mL/kg) per oral for 28 days. The rats' stomachs were examined for gastric toxicity using a stereomicroscope. The urine samples were analyzed using a proton nuclear magnetic resonance spectroscopy. Metabolites were systematically identified by exploring established databases and multivariate analyses to determine the spectral pattern of metabolites related to LDA-induced gastric toxicity.
RESULTS: Treatment with LDA resulted in gastric toxicity in 20/32 rats (62.5%). The orthogonal projections to latent structures discriminant analysis (OPLS-DA) model displayed a goodness-of-fit (R2Y) value of 0.947, suggesting near-perfect reproducibility and a goodness-of-prediction (Q2Y) of -0.185 with perfect sensitivity, specificity and accuracy (100%). Furthermore, the area under the receiver operating characteristic (AUROC) displayed was 1. The final OPLS-DA model had an R2Y value of 0.726 and Q2Y of 0.142 with sensitivity (100%), specificity (95.0%) and accuracy (96.9%). Citrate, hippurate, methylamine, trimethylamine N-oxide and alpha-keto-glutarate were identified as the possible metabolites implicated in the LDA-induced gastric toxicity.
CONCLUSION: The study identified metabolic signatures that correlated with the development of a low-dose Aspirin-induced gastric toxicity in rats. This pharmacometabolomic approach could further be validated to predict LDA-induced gastric toxicity in patients with coronary artery disease.
METHODS AND STUDY DESIGN: This cross-sectional study was conducted from 1 May to 30 June, 2013, in three rural divisions of Sabah (the Interior, the West Coast, and Kudat). Data regarding domestic iodised salt use and iodine-containing supplement consumption were obtained from respondents through face-to-face interviews; goitre enlargement was examined through palpation and graded according to the World Health Organization classification. Spot urine samples were also obtained to assess urinary iodine levels by using an in-house modified micromethod.
RESULTS: In total, 534 pregnant women participated. The prevalence of goitre was 1.0% (n=5), noted only in the West Coast and Kudat divisions. Although all pregnant women consumed iodised salt, overall median urinary iodine concentration was only 106 μg/L, indicating insufficient iodine intake, with nearly two-thirds of the women (60%) having a median urinary iodine concentrations of <150 μg/L.
CONCLUSIONS: Pregnant women from the rural divisions in Sabah still exhibit iodine deficiency disorder despite the mandatory universal salt iodisation programme. Iodine supplementation programmes targeting pregnant women are warranted.