A comprehensive Thai pharmacogenomics database (TPGxD-1): Phenotype prediction and variants identification in 942 whole-genome sequencing data.

Computational methods analyze genomic data to identify genetic variants linked to drug responses, thereby guiding personalized medicine. This study analyzed 942 whole-genome sequences from the Electricity Generating Authority of Thailand (EGAT) cohort to establish a population-specific pharmacogenomic database (TPGxD-1) in the Thai population. Sentieon (version 201808.08) implemented the GATK best workflow practice for variant calling. We then annotated variant call format (VCF) files using Golden Helix VarSeq 2.5.0 and employed Stargazer v2.0.2 for star allele analysis. The analysis of 63 very important pharmacogenes (VIPGx) reveals 85,566 variants, including 13,532 novel discoveries. Notably, we identified 464 known PGx variants and 275 clinically relevant novel variants. The phenotypic prediction of 15 VIPGx demonstrated a varied metabolic profile for the Thai population. Genes like CYP2C9 (9%), CYP3A5 (45.2%), CYP2B6 (9.4%), NUDT15 (15%), CYP2D6 (47%) and CYP2C19 (43%) showed a high number of intermediate metabolizers; CYP3A5 (41%), and CYP2C19 (9.9%) showed more poor metabolizers. CYP1A2 (52.7%) and CYP2B6 (7.6%) were found to have a higher number of ultra-metabolizers. The functional prediction of the remaining 10 VIPGx genes reveals a high frequency of decreased functional alleles in SULT1A1 (12%), NAT2 (84%), and G6PD (12%). SLCO1B1 reports 20% poor functional alleles, while PTGIS (42%), SLCO1B1 (4%), and TPMT (5.96%) showed increased functional alleles. This study discovered new variants and alleles in the 63 VIPGx genes among the Thai population, offering insights into advancing clinical pharmacogenomics (PGx). However, further validation is needed using other computational and genotyping methods.

An Increase in Vascular Stiffness Is Positively Associated With Mitochondrial Bioenergetics Impairment of Peripheral Blood Mononuclear Cells in the Older Adults.

The cardio-ankle vascular index (CAVI) is a noninvasive parameter reflecting vascular stiffness. CAVI correlates with the burden of atherosclerosis and future cardiovascular events. Mitochondria of peripheral blood mononuclear cells (PBMCs) have been identified as a noninvasive source for assessing systemic mitochondrial bioenergetics. This study aimed to investigate the relationship between CAVI values and mitochondrial bioenergetics of PBMCs in the older adults.. This cross-sectional study enrolled participants from the Electricity Generating Authority of Thailand between 2017 and 2018. A total of 1 640 participants with an ankle-brachial index greater than 0.9 were included in this study. All participants were stratified into 3 groups based on their CAVI values as high (CAVI ≥ 9), moderate (9 > CAVI ≥ 8), and low (CAVI < 8), in which each group comprised 702, 507, and 431 participants, respectively. The extracellular flux analyzer was used to measure mitochondrial respiration of isolated PBMCs. The mean age of the participants was 67.9 years, and 69.6% of them were male. After adjusted with potential confounders including age, sex, smoking status, body mass index, diabetes, dyslipidemia, hypertension, and creatinine clearance, participants with high CAVI values were independently associated with impaired mitochondrial bioenergetics, including decreased basal respiration, maximal respiration, and spare respiratory capacity, as well as increased mitochondrial reactive oxygen species. This study demonstrated that CAVI measurement reflects the underlying impairment of cellular mitochondrial bioenergetics in PBMCs. Further longitudinal studies are necessary to establish both a causal relationship between CAVI measurement and underlying cellular dysfunction.

Biological age as estimated by baseline circulating metabolites is associated with incident diabetes and mortality.

OBJECTIVES: It is unclear how metabolomic assessment of biological aging performs in non-White populations and whether such an approach can predict future mortality. We aimed to evaluate the application of serum metabolomics combined with machine learning methodologies to predict incident diabetes and mortality in a Thai population. DESIGN, SETTING AND PARTICIPANTS: We analyzed serum samples and mortality data over 11 years from among 454 participants with no previous history of diabetes and with a fasting plasma glucose ≥85th percentile (5.4 mmol/L) but <7 mmol/L. MEASUREMENTS: Untargeted serum metabolomics were assessed using liquid chromatography/mass spectrometry. A deep artificial neural network was used to predict biological age based on serum metabolite profiles and chronological age. RESULTS: The mean age of participants was 40.5 ± 6.4 years, and 70.8% were men. We found a significant positive correlation between metabolomic age and chronological age (r = 0.71, P < 0.001). After 5 years, 61 of 404 participants with available glycated hemoglobin status (15.1%) progressed to diabetes. Chronological age was associated with incident diabetes but was not significant (P = 0.08), after adjusting for BMI and sex. Metabolomic age was significantly related to incident diabetes after controlling for BMI and sex (P < 0.05). Over the 11-year follow-up, 10 participants died owing to non-accidental causes. When metabolomic age and chronological age were included together in the model, metabolomic age (but not chronological age) was associated with mortality, independent of age, sex, and BMI. Among all identifiable metabolites, beta-D-mannosylphosphodecaprenyl and phosphatidylserines were the five leading metabolites associated with mortality. CONCLUSION: We concluded that serum metabolomic profile was associated with incident diabetes as well as mortality over our 11-year study period, which may render it potentially useful in assessing biological aging in humans.

Periodontitis and hypertension are linked through systemic inflammation: A 5-year longitudinal study.

AIM: To investigate the associations between periodontitis and hypertension and potential mediation via systemic inflammation through a 5-year longitudinal study. MATERIALS AND METHODS: The severity and extent of periodontitis were determined using probing depth (PD). Oral hygiene was assessed using plaque scores. The associations between periodontal variables and 5-year blood pressure changes or incident hypertension were analysed using linear or Poisson regression, adjusting for potential confounders. Mediation analysis of two systemic inflammatory biomarkers, namely white blood cell count (WBC) and C-reactive protein (CRP) levels, was performed. RESULTS: The study population included 901 hypertension-free participants, aged 50-73 years. Greater mean PD, higher percentage of sites with PD ≥ 6 mm and poor oral hygiene were associated with elevated systolic blood pressure and increased hypertension risk (relative risks = 1.17 [95% confidence interval [CI]: 1.02-1.34], 1.13 [95% CI: 1.02-1.26] and 1.08 [95% CI: 1.03-1.13], respectively). Periodontitis and poor oral hygiene were associated with higher WBC and CRP levels (p < .05), which, in turn, were associated with increased hypertension risk (p < .05). WBC and CRP jointly mediated 14.1%-26.9% of the associations between periodontal variables and incident hypertension. CONCLUSIONS: Periodontitis and poor oral hygiene were associated with increased hypertension risk, and systemic inflammation was, in part, a mediator of these associations.

Development of Risk Prediction Models for Severe Periodontitis in a Thai Population: Statistical and Machine Learning Approaches.

BACKGROUND: Severe periodontitis affects 26% of Thai adults and 11.2% of adults globally and is characterized by the loss of alveolar bone height. Full-mouth examination by periodontal probing is the gold standard for diagnosis but is time- and resource-intensive. A screening model to identify those at high risk of severe periodontitis would offer a targeted approach and aid in reducing the workload for dentists. While statistical modelling by a logistic regression is commonly applied, optimal performance depends on feature selections and engineering. Machine learning has been recently gaining favor given its potential discriminatory power and ability to deal with multiway interactions without the requirements of linear assumptions. OBJECTIVE: We aim to compare the performance of screening models developed using statistical and machine learning approaches for the risk prediction of severe periodontitis. METHODS: This study used data from the prospective Electricity Generating Authority of Thailand cohort. Dental examinations were performed for the 2008 and 2013 surveys. Oral examinations (ie, number of teeth and oral hygiene index and plaque scores), periodontal pocket depth, and gingival recession were performed by dentists. The outcome of interest was severe periodontitis diagnosed by the Centre for Disease Control-American Academy of Periodontology, defined as 2 or more interproximal sites with a clinical attachment level ≥6 mm (on different teeth) and 1 or more interproximal sites with a periodontal pocket depth ≥5 mm. Risk prediction models were developed using mixed-effects logistic regression (MELR), recurrent neural network, mixed-effects support vector machine, and mixed-effects decision tree models. A total of 21 features were considered as predictive features, including 4 demographic characteristics, 2 physical examinations, 4 underlying diseases, 1 medication, 2 risk behaviors, 2 oral features, and 6 laboratory features. RESULTS: A total of 3883 observations from 2086 participants were split into development (n=3112, 80.1%) and validation (n=771, 19.9%) sets with prevalences of periodontitis of 34.4% (n=1070) and 34.1% (n=263), respectively. The final MELR model contained 6 features (gender, education, smoking, diabetes mellitus, number of teeth, and plaque score) with an area under the curve (AUC) of 0.983 (95% CI 0.977-0.989) and positive likelihood ratio (LR+) of 11.9 (95% CI 8.8-16.3). Machine learning yielded lower performance than the MELR model, with AUC (95% CI) and LR+ (95% CI) values of 0.712 (0.669-0.754) and 2.1 (1.8-2.6), respectively, for the recurrent neural network model; 0.698 (0.681-0.734) and 2.1 (1.7-2.6), respectively, for the mixed-effects support vector machine model; and 0.662 (0.621-0.702) and 2.4 (1.9-3.0), respectively, for the mixed-effects decision tree model. CONCLUSIONS: The MELR model might be more useful than machine learning for large-scale screening to identify those at high risk of severe periodontitis for periodontal evaluation. External validation using data from other centers is required to evaluate the generalizability of the model.

Longitudinal study of vitamin D status among Thai individuals in a sun-abundant country.

Background: Vitamin D deficiency is a major public health problem worldwide, even in countries with abundant sunshine. Understanding the risk factors for vitamin D deficiency is important to inform public health recommendations. We conducted a longitudinal analysis of vitamin D status in Thai individuals to assess changes in vitamin D status over time and identify potential determinants. Study design: This study is a long term prospective cohort study. Methods: Of the 1239 participants who were employees of the Electricity Generating Authority of Thailand, serum 25-hydroxyvitamin D (25(OH)D) levels were measured by liquid chromatography/tandem mass spectrometry from samples collected in 2009 and 2019. Results: There was a significant 14.8% increase in serum total 25(OH)D (P < 0.001) from 2009 to 2019, which resulted from significant increases in both 25(OH)D3 and 25(OH)D2. The epimeric form of 25(OH)D2 also increased significantly, while there was no increase in the epimeric form of 25(OH)D3. A univariate analysis showed significant associations between increased total 25(OH)D and increasing age, male sex, and lower body mass index. After controlling for baseline vitamin D status, multivariate regression analyses found that the direction of association and significance from univariate analyses persisted for total 25(OH)D and 25(OH)D3. However, a univariate association found between female sex and an increase in 25(OH)D2 was not significant in multivariate regression analysis. Conclusions: A long-term trend of improved vitamin D status was found among Thai adult individuals over a 10-year period; however, improvements were less noticeable in women.

Associations between residential greenness and air pollution and the incident metabolic syndrome in a Thai worker cohort.

Increasing air pollution and decreasing exposure to greenness may contribute to the metabolic syndrome (MetS). We examined associations between long-term exposure to residential greenness and air pollution and MetS incidence in the Bangkok Metropolitan Region, Thailand. Data from 1369 employees (aged 52-71 years) from the Electricity Generating Authority of Thailand cohort from 2002 to 2017 were analyzed. The greenness level within 500 m of each participant's residence was measured using the satellite-derived Normalized Difference Vegetation Index (NDVI) and Enhanced Vegetation Index (EVI). The kriging approach was used to generate the average concentration of each air pollutant (PM10, CO, SO2, NO2, and O3) at the sub-district level. The average long-term exposure to air pollution and greenness for each participant was calculated over the same period of person-time. Cox proportional hazards models were used to analyze the greenness-air pollution-MetS associations. The adjusted hazard ratio of MetS was 1.42 (95% confidence interval (CI): 1.32, 1.53), 1.22 (95% CI: 1.15, 1.30), and 2.0 (95% CI: 1.82, 2.20), per interquartile range increase in PM10 (9.5 µg/m3), SO2 (0.9 ppb), and CO (0.3 ppm), respectively. We found no clear association between NDVI or EVI and the incidence of MetS. On the contrary, the incident MetS was positively associated with NDVI and EVI for participants exposed to PM10 at concentrations more than 50 µg/m3. In summary, the incidence of MetS was positively associated with long-term exposure to air pollution. In areas with high levels of air pollution, green spaces may not benefit health outcomes.

Gaps in the Care of Subjects with Familial Hypercholesterolemia: Insights from the Thai Familial Hypercholesterolemia Registry.

AIMS: Familial hypercholesterolemia (FH) is currently underdiagnosed and undertreated. The establishment of a FH registry could facilitate a deeper understanding of this disease. We described the clinical characteristics of subjects with FH from the Thai FH Registry, compared our data with the regional and global data, and identified gaps in the care of these subjects. METHODS: A multicenter, nationwide prospective FH registry was established in Thailand. Our data were compared with those of the European Atherosclerosis Society-FH Studies Collaboration. Multiple logistic regression analyses were performed for variables associated with lipid-lowering medication (LLM) use and the attainment of low-density lipoprotein-cholesterol (LDL-C) goal. RESULTS: The study includes 472 subjects with FH (mean age at FH diagnosis: 46±12 years, 61.4% women). A history of premature coronary artery disease was found in 12%. The percentage of LLM use in subjects with a Dutch Lipid Clinic Network score of ≥ 6 (probable or definite FH) in our registry (64%) was slightly lower than the regional data but higher than the global data. Among those who received statins, 25.2% and 6.4% achieved LDL-C levels of ＜100 mg/dL and ＜70 mg/dL, respectively. Women with FH were less likely to achieve LDL-C ＜70 mg/dL (adjusted odds ratio: 0.22, 95% confidence interval: 0.06-0.71, p=0.012). CONCLUSIONS: FH in Thailand was diagnosed late, and treatment was inadequate for the majority of subjects. Women with FH were less likely to achieve LDL-C goals. Our insights could potentially help raise awareness and narrow the gap in patient care.

Residential greenness and kidney function: A cohort study of Thai employees.

Higher residential greenness is associated with a lower risk of chronic kidney disease, but evidence on the association between greenness exposure and kidney function has not been conducted. Using cohort data from Electricity Generating Authority of Thailand (EGAT) employees, we investigated the association between long-term exposure to greenness and kidney function using estimated glomerular filtration rate (eGFR) in Bangkok Metropolitan Region (BMR), Thailand. We analyzed data from 2022 EGAT workers (aged 25-55 years at baseline) from 2009 to 2019. The level of greenness was calculated using the satellite-derived Enhanced Vegetation Index (EVI) and Normalized Difference Vegetation Index (NDVI). From 2008 to 2019, the average concentration of each air pollutant (PM10, O3, NO2, SO2, and CO) at the sub-district level in BMR was generated using the Kriging method. Long-term exposure for each participant was defined as the 1-year average concentrations before the date of the physical examination in 2009, 2014, and 2019. We employed linear mixed effects models to evaluate associations of NDVI and EVI with eGFR. The robustness of the results was also tested by including air pollutants in the models. After relevant confounders were controlled, the interquartile range increase in NDVI was associated with higher eGFR [1.03% (95%CI: 0.33, 1.74)]. After PM10 and SO2 were included in the models, the associations between NDVI and eGFR became weaker. The additions of O3, NO2, and CO strengthened the associations between them. In contrast, we did not find any association between EVI and eGFR. In conclusion, there was a positive association between NDVI and eGFR, but not for EVI. Air pollutants had a significant impact on the relationship between NDVI and eGFR. Additional research is needed to duplicate this result in various settings and populations to confirm our findings.

Association of body mass index and dietary intake with mild cognitive impairment and dementia: a retrospective cohort study.

BACKGROUND: The prevalence of cognitive impairment in older adults is gradually increasing, and this is leading to many adverse outcomes. Common causes of cognitive impairment in advancing age are mild cognitive impairment (MCI) and dementia. However, how the nutritional status and nutrient intake are related to MCI and dementia is controversial. Therefore, we aimed to evaluate the association of body mass index (BMI) and dietary intake with the risk of MCI and dementia. METHODS: This retrospective cohort study involved 821 participants aged ≥ 50 years from a previous population-based cohort study: the Electricity Generating Authority of Thailand (EGAT) study in 2013-2014 (baseline) and 2018-2019 (follow-up). Dietary intake was recorded using a 12-month self-reported food frequency questionnaire. MCI and dementia were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria using the Montreal Cognitive Assessment with ADL and the Kessler Psychological Distress Scale (K10) at study entry and at the 5-year follow-up. RESULTS: Among the 821 participants, the mean age was 60.0 ± 4.3 years, and the incidence rate of MCI and dementia was 42.5 and 11.2 per 1,000 person-years, respectively. The rate of MCI and dementia was higher in participants aged ≥ 60 years and with an education level of < 7 years. The rate of MCI was also higher in those with a BMI of ≥ 25 kg/m2 and type 2 diabetes. Compared to BMI 18.5-22.9 kg/m2, BMI of ≥ 25 kg/m2 (odds ratio 1.91 [95% confidence interval, 1.12-3.26], p < 0.001) was associated with an increased risk of MCI after adjusted for age, education level, and type 2 diabetes. Regarding dietary intake, fresh red meat consumption was inversely associated with the risk of MCI (p = 0.037) and dementia (p = 0.011) after adjusting for age, education level, type 2 diabetes, and BMI. CONCLUSION: Obesity was associated with a greater risk of MCI. Moreover, low consumption of fresh red meat could be a risk factor for MCI and dementia. Further studies are required to confirm and explain these findings.

Increased Efficiency of Mitochondrial Coupling With a Reduction in Other Mitochondrial Respiratory Parameters in Peripheral Blood Mononuclear Cells Is Observed in Older Adults.

Mitochondrial dysfunction is a factor potentially contributing to the Aging process. However, evidence surrounding changes in mitochondrial function and aging is still limited; therefore, this study aimed to investigate further the association between them. Possible confounding factors were included in the statistical analysis to explore the possibility of any independent associations. One thousand seven hundred and sixty-nine participants (619 middle-aged adults [age < 65] and 1,150 older adults [age ≥ 65]) from the Electricity Generating Authority of Thailand were enrolled in the study. The clinical characteristics and medical history were collected. Peripheral blood mononuclear cells (PBMCs) were isolated from venous blood and used for analysis of mitochondrial function. Several parameters pertinent to mitochondrial respiration including non-mitochondrial respiration, basal respiration, maximal respiration, proton leak, and spare respiratory capacity were found to be two to three times lower in the mitochondria isolated from the cells of older adults. Interestingly, the mitochondrial ATP production was only slightly reduced, and the percentage of coupling efficiency of PBMC mitochondria was significantly higher in the older adult group. The mitochondrial mass and oxidative stress were significantly reduced in older adult participants; however, the ratio of oxidative stress to mass was significantly increased. The association of these parameters with age was still shown to be the same from the outcome of the multivariate analyses. The mitochondrial functions and mitochondrial mass in PBMCs were shown to decline in association with age. However, the upregulation of mitochondrial oxidative stress production and mitochondrial coupling efficiency might indicate a compensatory response in mitochondria during aging.

Validity of Simple Self-Reported Periodontal Status Questions.

OBJECTIVE: The aim of this research was to evaluate the validity of the questions developed by Thai periodontists on self-reported periodontal status and symptoms in identifying severe periodontitis amongst adults in Thailand. METHODS: Registered Electricity Generating Authority of Thailand (EGAT) employees completed medical examinations and full-mouth periodontal examinations. They also were interviewed using a self-reported questionnaire that was developed by Thai periodontists. The questions pertained to their periodontal status and symptoms comprising swollen gums, bad breath, loose teeth, bleeding on brushing, painful gums, and pus or abscesses. The participants were categorised as having nonsevere and severe periodontitis according to the Centers for Disease Control and Prevention in partnership with the American Academy of Periodontology (CDC/AAP) case definitions. Self-reported periodontal status and symptom results were compared with actual periodontal status. The area under the receiver operating characteristic curve (AUROCC), sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated. RESULTS: A total of 1393 EGAT employees participated in this study. The questions on self-reported periodontal status and all symptoms poorly identified patients with severe periodontitis, with an AUROCC of 0.52 to 0.60. The sensitivity was 5.0% to 40.2%; however, the specificity was good, at 73.2% to 99.1%. The validity of the self-reported questions was comparable amongst the sex, education, and income subgroups. CONCLUSIONS: This study demonstrated that self-reported periodontal status and symptoms were inadequate in identifying patients with severe periodontal disease.

Effectiveness and Safety of Direct Oral Anticoagulants in Thai Patients with Atrial Fibrillation: A Real-World Retrospective Cohort Study.

BACKGROUND: Direct oral anticoagulants (DOACs) are commonly used to prevent stroke and systemic embolism in patients with atrial fibrillation (AF). However, studies into their effectiveness and safety in the Thai population have so far been limited. OBJECTIVES: To study the effectiveness and safety of warfarin and DOACs among Thai AF patients. METHODS: A retrospective cohort study was conducted on AF patients at Ramathibodi Hospital from 2013 to 2018. All patients were followed for at least 1 year. Relevant clinical information was collected and compared between AF patient groups receiving warfarin, dabigatran, rivaroxaban, and apixaban. The primary outcome was a composite of major bleeding, ischemic stroke, and systemic thromboembolism. The secondary outcomes were all-cause mortality and disease-specific mortality caused by major bleeding, ischemic stroke, and systemic thromboembolism. RESULTS: A total of 1680 AF patients were enrolled in the study (warfarin 1193, apixaban 140, dabigatran 193, rivaroxaban 114). The estimated incidence of composite outcome was 16% [95% CI, 14-18%] and 12.4% [95% CI, 9.4-15.3%] in the warfarin and DOAC group, respectively, given a number needed to treat of 28 [95% CI, 3-52]. Compared with warfarin, DOACs were associated with both lower rate of all-cause mortality (4.9% [22/447] vs 8% [98/1193]) and lower disease-specific mortality (0.4% [2/447] and 1% [12/1193]). CONCLUSIONS: This study suggests DOACs were associated with a lower risk of major bleeding, ischemic stroke, and systemic thromboembolism compared to warfarin in Thai patients with AF. Patients receiving DOAC also had a lower rate of all-cause mortality and disease-specific mortality.

Mendelian randomization study of the effect of coronary artery calcification on atherosclerotic cardiovascular diseases.

Calcium calcification in the wall of arteries (CAC) leads to a higher risk of atherosclerosis related outcomes, especially myocardial infarction (MI). Nevertheless, the causal role of CAC on other related outcomes is unclear. In this study, we used Mendelian randomization (MR) to systematically investigate the causal role of CAC across a broad range of atherosclerotic cardiovascular diseases including coronary heart disease, angina, MI, ischemic heart disease, stroke, and peripheral vascular disease. Publicly available data from the UK biobank and other data sources were used. Using the two-sample Mendelian randomization (MR) approach, we applied 3 MR models including the inverse variance weighted, the weighted-median, and the weighted-mode methods. Eight SNPs associated with CAC were selected as instrumental variables. We observed causal evidence of CAC on MI consistently across all MR models (PIVW = 1.0 × 10-4, PW-Median = 1.1 × 10-4, PW-Mode = 3.8 × 10-2) and this causation is shown in an acute transmural MI of inferior wall (PIVW = 1.5 × 10-4, PW-Median = 4.8 × 10-5, PW-Mode = 3.2 × 10-2) but not consistently observed in an anterior wall. As each site of acute MI was suggested to have relatively specific mechanisms, our finding suggested that the causal role of CAC on MI is in an inferior wall possibly as a consequence of large calcification from a prolonged process, whereas non-calcified artery plaque or other underlying mechanisms may predominantly play role in an anterior infarction during an advanced atherosclerotic process.

Using real world evidence to generate cost-effectiveness analysis of fibrinolytic therapy in patients with ST-segment elevation myocardial infarction in Thailand.

Background: Due to limited access to primary percutaneous coronary intervention for the management of ST-segment elevation myocardial infarction (STEMI) in low-to-middle-income countries (LMICs), fibrinolysis serves as a vital alternative reperfusion therapy. Among fibrinolytic agents, the cost-effectiveness of tenecteplase (TNK) in LMICs as compared to streptokinase (SK) for STEMI management remains unknown. Methods: Cost-effectiveness was analyzed using a hybrid model consisting of short-term analysis (30-days decision tree model) and long-term analysis (Markov model). Both health care provider and societal perspectives over a lifetime horizon with 3% discount rate were considered. Input parameters were obtained from Thailand's national health database, a network meta-analysis and literature review. Outcome measure was an incremental cost-effectiveness ratio (ICER) determined by an incremental cost per quality-adjusted life years (QALY) gain. An ICER of less than $5,590 per QALY gain is considered cost-effective. Series of sensitivity analyses were also performed. Findings: From the societal perspective, TNK increases cost by $827 and increases QALY by 0·173. Thus, the ICER is $4,777 per QALY gained. Similarly, the ICER from health care provider perspective is $4,664 per QALY gained. In the probabilistic sensitivity analysis, using 5,590 USD per QALY as threshold, the probability of TNK being cost-effective was 83% from both perspectives. The most influential parameters were risk ratio of death for treatment with TNK compared to SK and drug cost of TNK. Interpretation: In a resource-limited country like Thailand, tenecteplase is a cost-effective fibrinolytic drug for treatment of STEMI compared to streptokinase. Funding: None.

Long-Term Effects of Cigarette Smoking on All-Cause Mortality and Cardiovascular Outcomes in Thai Population: Results From a 30-Year Cohort Study.

Despite the overwhelming evidences on the health consequences of smoking, studies in Asian population in low-to-middle income countries are very limited. Baseline data of a prospective cohort study were collected in year 1985. Endpoints regarding all-cause mortality and major adverse cardiovascular events (MACE) were followed for 30 years. Cox proportional hazard models were used for analysis. Participants had an average age of 43 years, 23% were female, and 43% were current smokers. All-cause mortality was significantly higher in ex-smokers (hazard ratio [HR] 1.32) and current smokers (HR 1.70) when compared with never smokers. Participants with any history of smoking had significantly higher risk of developing MACE. Furthermore, all-cause death, cardiovascular death, and MACE increased with increasing pack years. Statistically significant dose-response relationships were established. Therefore, cigarette smoking increased the risk of all-cause mortality, cardiovascular mortality, and MACE in Thai population. Results emphasized the importance of tobacco control in Thailand.

Bone Mineral Density and Trabecular Bone Score in Predicting Vertebral Fractures in Male Employees of the Electricity Generating Authority of Thailand.

Purpose: Osteoporotic VF is frequently asymptomatic and affects not only women but also men. Identifying patients at risk is essential for early management and prevention. BMD and the TBS are measurements of bone strength and trabecular microarchitecture, respectively. Their role in VF prediction in men is less well-studied. We determined the BMD and TBS predictive ability for osteoporotic VF in men. Methods: A total of 115 male participants of the Electricity Generating Authority of Thailand (EGAT) cohorts without a history of VF who completed the baseline BMD and TBS measurements in 2012 and a thoracolumbar spine radiograph in 2017 were recruited. The VF was assessed using the Genant semiquantitative method. Logistic regression analysis was performed to identify factors associated with the fracture. The area under the receiving operator curve (AUC) was analyzed to define VF predictive ability. Results: Forty subjects (34.78%) had VFs. The unadjusted relative risks (95% confidence interval) for VF for one standard deviation decrease in the TBS and low TBS were 1.319 (1.157-1.506) and 2.347 (1.496-3.682), respectively, and remained significant after BMD and age adjustment. For VF prediction, combined models had a greater AUC than models predicted from a single variable. The use of low TBS, femoral neck BMD, and age provided the best AUC (0.693). Conclusion: BMD and the TBS could predict osteoporotic VF in male EGAT employees. The use of both BMD and the TBS in the VF prediction process improved predictive ability.

Causal relationship of excess body weight on cardiovascular events through risk factors.

Excess body weight is associated with cardiovascular events (CVEs) and premature death. This study aimed to find the causal pathways between excess body weight and CVEs through risk factors in a general adult population. A total of 7921 employees of the Electricity Generating Authority of Thailand were enrolled during 1997-2009. Baseline characteristics and blood test results were collected. A body mass index (BMI) ≥ 23 kg/m2, using WHO criteria for Asians was defined as excess body weight. A mediation analysis was applied to assess potential causal pathways. BMI ≥ 23 kg/m2 was considered as an independent variable, whereas diabetes mellitus (DM), hypertension (HT), and chronic kidney disease (CKD) were considered as mediators, and CVEs (i.e., fatal and non-fatal coronary artery disease or stroke) were considered as the outcomes. The prevalence of BMI ≥ 23 kg/m2, DM, HT, and CKD were 62.7%, 7.8%, 28.1% and 11.8% respectively. During an average of 17.2 ± 5.5 years follow-up, subjects with BMI ≥ 23 kg/m2 compared with those with lower BMIs more frequently developed CVEs (9.4 vs 6.2%, P < 0.001). The effects of BMI ≥ 23 kg/m2 on CVEs were mediated indirectly through DM and HT with significant ORs of 1.61 (1.34, 2.09) and 1.57 (1.39, 1.80), respectively. The indirect effect of CKD on CVEs was significantly increased if mediated through DM → HT or HT [ORs of 1.17 (1.09, 1.32) and 1.20 (1.10, 1.32), respectively]. Subjects with excess body weight were prone to develop CVEs which were mediated indirectly through DM and HT. The effect of CKD on CVEs was small but enhanced if it occurred as a complication of DM or HT.

Long-term air pollution exposure and decreased kidney function: A longitudinal cohort study in Bangkok Metropolitan Region, Thailand from 2002 to 2012.

BACKGROUND: Kidney dysfunction is considered a cardiovascular risk factor. However, few longitudinal studies have examined the effects of air pollution on kidney function. We evaluated associations between long-term air pollution exposure and estimated glomerular filtration rate (eGFR) using data from a cohort of the Electricity Generating Authority of Thailand (EGAT) study in Bangkok Metropolitan Region, Thailand. METHODS: This longitudinal study included 1839 subjects (aged 52-71 years in 2002) from the EGAT1 cohort study during 2002-2012. eGFR, based on creatinine, was measured in 2002, 2007, and 2012. Annual mean concentrations of air pollutants (i.e., particulate matter with an aerodynamic diameter ≤10 µm (PM10), ozone (O3), nitrogen dioxide (NO2), sulfur dioxide (SO2), and carbon monoxide (CO)) prior to a measurement of creatinine were assessed with the ordinary kriging method. Mixed-effect linear regression models were used to assess associations between air pollutants and eGFR, while controlling for potential covariates. eGFR values are expressed as percent change per interquartile range (IQR) increments of each pollutant. RESULTS: Lower eGFR was associated with higher concentrations of PM10 (-1.99%, 95% confidence interval (CI): -3.33, -0.63), SO2 (-4.89%, 95%CI: -6.69, -3.07), and CO (-0.97%, 95%CI: -1.96, 0.03). However, after adjusting for temperature, relative humidity, PM10, and SO2, no significant association was observed between CO and eGFR. CONCLUSIONS: Our findings support the hypothesis that long-term exposure to high concentrations of PM10 and SO2 is associated with the progression of kidney dysfunction in subjects of the EGAT cohort study.