The hidden financial catastrophe of chronic kidney disease under universal coverage and Thai "Peritoneal Dialysis First Policy".

Objective: Universal health coverage can decrease the magnitude of the individual patient's financial burden of chronic kidney disease (CKD), but the residual financial hardship from the patients' perspective has not been well-studied in low and middle-income countries (LMICs). This study aimed to evaluate the residual financial burden in patients with CKD stage 3 to dialysis in the "PD First Policy" under Universal Coverage Scheme (UCS) in Thailand. Methods: This multicenter nationwide cross-sectional study in Thailand enrolled 1,224 patients with pre-dialysis CKD, hemodialysis (HD), and peritoneal dialysis (PD) covered by UCS and other health schemes for employees and civil servants. We interviewed patients to estimate the proportion with catastrophic health expenditure (CHE) and medical impoverishment. The risk factors associated with CHE were analyzed by multivariable logistic regression. Results: Under UCS, the total out-of-pocket expenditure in HD was over two times higher than PD and nearly six times higher than CKD stages 3-4. HD suffered significantly more CHE and medical impoverishment than PD and pre-dialysis CKD [CHE: 8.5, 9.3, 19.5, 50.0% (p < 0.001) and medical impoverishment: 8.0, 3.1, 11.5, 31.6% (p < 0.001) for CKD Stages 3-4, Stage 5, PD, and HD, respectively]. In the poorest quintile of UCS, medical impoverishment was present in all HD and two-thirds of PD patients. Travel cost was the main driver of CHE in HD. In UCS, the adjusted risk of CHE increased in PD and HD (OR: 3.5 and 16.3, respectively) compared to CKD stage 3. Conclusions: Despite universal coverage, the residual financial burden remained high in patients with kidney failure. CHE was considerably lower in PD than HD, although the rates remained alarmingly high in the poor. The "PD First' program" could serve as a model for other LMICs. However, strategies to minimize financial distress should be further developed, especially for the poor.

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.

Economic evaluation of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) for stroke prevention in patients with atrial fibrillation: a systematic review and meta-analysis.

OBJECTIVES: To assess cost-effectiveness of direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKAs) for stroke prevention in atrial fibrillation (AF) by pooling incremental net benefits (INBs). DESIGN: Systematic review and meta-analysis. SETTING: We searched PubMed, Scopus and Centre for Evaluation of Value and Risks in Health Registry from inception to December 2019. PARTICIPANTS: Patients with AF. MAIN OUTCOME MEASURES: The INB was defined as a difference of incremental effectiveness multiplied by willing to pay threshold minus the incremental cost; a positive INB indicated favour treatment. These INBs were pooled (stratified by level of country income, perspective, time-horizon, model types) with a random-effects model if heterogeneity existed, otherwise a fixed effects model was applied. Heterogeneity was assessed using Q test and I2 statistic. Risk of bias was assessed using the economic evaluations bias (ECOBIAS) checklist. RESULTS: A total of 100 eligible economic evaluation studies (224 comparisons) were included. For high-income countries (HICs) from a third-party payer (TPP) perspective, the pooled INBs for DOAC versus VKA pairs were significantly cost-effective with INBs (95% CI) of $6632 ($2961.67 to $10 303.72; I2=59.9%), $6353.24 ($4076.03 to $8630.45; I2=0%), $7664.58 ($2979.79 to $12 349.37; I2=0%) and $8573.07 ($1877.05 to $15 269.09; I2=0%) for dabigatran, apixaban, rivaroxaban and edoxaban relative to VKA, respectively but only dabigatran was significantly cost-effective from societal perspective (SP) with an INB of $11 746.96 ($2429.34 to $21 064.59; I2=52.4%). The pooled INBs of all comparisons for upper-middle income countries (UMICs) were not significantly cost-effective. The ECOBIAS checklist indicated that risk of bias was mostly low for most items with the exception of five items which should be less influenced on pooling INBs. CONCLUSIONS: Our meta-analysis provides comprehensive economic evidence that allows policy makers to generalise cost-effectiveness data to their local context. All DOACs may be cost-effective compared with VKA in HICs with TPP perspective. The pooling results produced moderate to high heterogeneity particularly in UMICs. Further studies are required to inform UMICs with SP. PROSPERO REGISTERATION NUMBER: CRD 42019146610.

Role of MT1A Polymorphism and Environmental Mercury Exposure on the Montreal Cognitive Assessment (MoCA).

PURPOSE: Many age-related structural and functional changes in the brain have important consequences. Long-term exposure to mercury and the impact of functional polymorphisms of metal-regulating proteins such as metallothioneins (MTs) can result in neurological-neurobehavioral effects in elderly individuals. Therefore, the aims of this study are to examine the associations between biomarkers of mercury exposure and cognitive impairment and to investigate the effect of the rs8052394 single nucleotide polymorphism (SNP) of the potential modifier gene MT1A on different domains of the Montreal Cognitive Assessment (MoCA). MATERIALS AND METHODS: We studied 436 participants aged ≥55 years from the Electricity Generating Authority of Thailand study. They underwent a physical examination, an extensive cognitive assessment with the MoCA (cutoff <26 points), and a biochemical analysis related to diabetes and dyslipidemia. The blood mercury level was determined by inductively coupled plasma mass spectrometry. Genotyping of the MT1A rs8052394 SNP was performed by the restriction fragmentation length polymorphism method. RESULTS: The mean age of the study population was 58.8±3.01 years, and most had ≥12 years of education (75.7%). The primary study finding was that the prevalence of mild cognitive impairment (MCI) in older Thai adults was 39.7%. The frequency distributions of the G allele of the rs8052394 SNP of the MT1A gene were significantly associated with the total and sub-domain MoCA scores. The prevalence of MCI was significantly associated with increased age, hypertriglyceridemia, hyperhomocysteinemia, the third tertile of blood mercury concentration, and the rs8052394 variant genotype of MT1A (P values for all odds ratios <0.05). CONCLUSION: These findings suggested that neurocognitive effects associate with mercury exposure and genetic susceptibility in toxicokinetics. Public health strategies can be used to implement as a comprehensive action plan to educate vulnerable populations on how to reduce mercury exposure. Concurrently, impact of such genetic predisposition requires replication for identifying and protecting susceptible individuals from mercury toxicity.

Long-term effects of socioeconomic status on the incidence of decreased glomerular filtration rate in a Southeast Asian cohort.

BACKGROUND: There is limited information on the role of low socioeconomic status (SES) in the development of new chronic kidney disease (CKD) in the general population, especially from developing countries. This study will test the hypothesis that low SES increases the risk of incidence of decreased glomerular filtration rate (GFR, used as an estimate for CKD) in a Thai worker cohort. METHOD: In this prospective, longitudinal observational study, we evaluated the association of income and educational attainment on incident decreased GFR (iGFR <60 mL/min/1.73 m2) over a 27-year period in employees of Electricity Generating Authority of Thailand. In 1985, subjects participated in a health survey and were re-examined in 1997, 2002, 2007 and 2012. Education was classified into three categories: low, 0-8th grade; medium, 9-12th grade; and high, >12th grade. Income was categorised as follows: low <10 000 Thai Baht (THB)/month; medium, 10 000-20 000 THB/month; and high, >20 000 THB/month. HRs of iGFR<60 mL/min/1.73 m2 were estimated using Cox interval-censored models with high income or education as the reference groups after adjustments for clinical risk factors. RESULTS: Participants (n=3334) were followed for 23 (15, 27) years. When evaluated separately, both education and income were risk factors for iGFR<60 mL/min/1.73 m2 (adjusted HR education: medium-1.26 (95% CI 1.13 to1.42) and low-1.57 (95% CI 1.36 to 1.81) and adjusted HR income: medium-1.21 (95% CI 0.97 to 1.50) and low-1.47 (95% CI 1.18 to 1.82)). When both income and education were included together, low and medium education remained independently associated with iGFR<60 mL/min/1.73 m2. CONCLUSIONS: Low education was independently associated with increased risk of decreased GFR in a Thai worker population. Strategies to identify risk factors among low SES may be useful to prevent early CKD.

Cost-effectiveness analysis of patient self-testing therapy of oral anticoagulation.

Patient Self-testing (PST) could be an option for present anticoagulation therapy monitoring, but current evidence on its cost-effectiveness is limited. This study aims to estimate the cost-effectiveness of PST to other different care approaches for anticoagulation therapy in Thailand, a low-to-middle income country (LMIC). A Markov model was used to compare lifetime costs and quality-adjusted life years (QALYs) accrued to patients receiving warfarin through PST or either anticoagulation clinic (AC) or usual care (UC). The model was populated with relevant information from literature, network meta-analysis, and database analyses. Incremental cost-effectiveness ratios (ICERs) were presented as the year 2015 values. A base-case analysis was performed for patients at age 45-year-old. Sensitivity analyses including one-way and probabilistic sensitivity analyses (PSA) were constructed to determine the robustness of the findings. From societal perspective, PST increased QALY by 0.87 and costs by 112,461 THB compared with UC. Compared with AC, PST increased QALY by 0.161 and costs by 21,019 THB. The ICER with PST was 128,697 (3625 USD) and 130,493 THB (3676 USD) per QALY gained compared with UC and AC, respectively. The probability of PST being cost-effective is 74.1% and 51.9%, compared to UC and AC, respectively, in Thai context. Results were sensitive to the efficacy of PST, age and frequency of hospital visit or self-testing. This analysis suggested that PST is highly cost-effective compared with usual care and less cost-effective against anticoagulation clinic. Patient self-testing strategy appears to be economically valuable to include into healthcare system within the LMIC context.

Cost-effectiveness analysis of pharmacogenetic-guided warfarin dosing in Thailand.

INTRODUCTION: Pharmacogenetic (PGx) test is a useful tool for guiding physician on an initiation of an optimal warfarin dose. To implement of such strategy, the evidence on the economic value is needed. This study aimed to determine the cost-effectiveness of PGx-guided warfarin dosing compared with usual care (UC). METHODS: A decision analytic model was used to compare projected lifetime costs and quality-adjusted life years (QALYs) accrued to warfarin users through PGx or UC for a hypothetical cohort of 1,000 patients. The model was populated with relevant information from systematic review, and electronic hospital-database. Incremental cost-effectiveness ratios (ICERs) were calculated based on healthcare system and societal perspectives. All costs were presented at year 2013. A series of sensitivity analyses were performed to determine the robustness of the findings. RESULTS: From healthcare system perspective, PGx increases QALY by 0.002 and cost by 2,959 THB (99 USD) compared with UC. Thus, the ICER is 1,477,042 THB (49,234 USD) per QALY gained. From societal perspective, PGx results in 0.002 QALY gained, and increases costs by 2,953 THB (98 USD) compared with UC (ICER 1,473,852 THB [49,128 USD] per QALY gained). Results are sensitive to the risk ratio (RR) of major bleeding in VKORC1 variant, the efficacy of PGx-guided dosing, and the cost of PGx test. CONCLUSION: Our finding suggests that PGx-guided warfarin dosing is unlikely to be a cost-effective intervention in Thailand. This evidence assists policy makers and clinicians in efficiently allocating scarce resources.

Prevalence of Dyslipidemia and Management in the Thai Population, National Health Examination Survey IV, 2009.

This study determined the prevalence and management of dyslipidemia in Thai adults using data from the Thai National Health Examination Survey IV in 2009. Dyslipidemia was defined based on the Third Adult Treatment Panel guidelines. A total of 19,021 adults aged 20 yr and over were included. Mean (SE) levels of total cholesterol, HDL-C, LDL-C, and triglycerides were 206.4 (1.03), 46.9 (0.34), 128.7 (1.09), and 131.4 (2.20) mg/dL, respectively. Prevalence of high LDL-C, low HDL-C, and high triglycerides were 29.6 %, 47.1 %, and 38.6%, respectively. Compared with individuals in the north and northeast, residents in Bangkok and Central region had significant higher levels of LDL-C but lower level of HDL-C. Triglyceride level was the highest in the northeast residents. Overall, 66.5% of Thais had some forms of dyslipidemia. Awareness and treatment of high LDL-C among those with high LDL-C were 17.8% and 11.7%, respectively. Among individuals aware of high LDL-C, those at highest CHD risk compared with those at low risk had higher percentage of treatment (73.1% versus 51.7%, resp.) but lower percentage of control at goal (32.9% versus 76.4%, resp.). Various forms of dyslipidemia are common in Thai adults, with a low level of awareness and treatment of high LDL-C.

Long-term cost effectiveness of ticagrelor in patients with acute coronary syndromes in Thailand.

OBJECTIVES: To evaluate the long-term cost-effectiveness of ticagrelor and ASA versus generic and branded clopidogrel and ASA in patients with ACS based on a Thai cost database. METHODS: A one-year decision tree and a long-term Markov model were constructed to estimate lifetime costs and quality-adjusted life years (QALYs). For the first year, data from PLATO (NCT00391872) were used to estimate the rate of cardiovascular events, resource use, and QALYs. For year 2 onwards, clinical effectiveness was estimated conditional on individual health states that occurred during the first year. RESULTS: In the base-case analysis, the incremental cost-effectiveness ratio (ICER) with ticagrelor was 292,504 ($9,476) and 60,055 ($1,946) THB($)/QALY compared with generic and branded clopidogrel, respectively. The probability of ticagrelor being cost-effective was above 99% at a threshold of 160,000 THB/QALY compared with branded clopidogrel. CONCLUSIONS: This health economic analysis provides cost effectiveness data for ticagrelor compared with both generic and branded clopidogrel in Thailand. Based on this analysis, it appears that ticagrelor is an economically valuable treatment for ACS compared with branded clopidogrel within the Thai context.

Validity of the Thai EQ-5D in an occupational population in Thailand.

PURPOSE: To assess the construct validity of the Thai EuroQoL (EQ-5D) among an occupational population in Thailand. METHODS: Data were derived from a large cohort study among employees of the Electricity Generating Authority of Thailand. In 2008 and 2009, 4,850 participants completed the Thai EQ-5D and Short-Form 36 version 2 (SF-36v2). Thai preferences weights were used to convert EQ-5D health states into EQ-5D index scores. Construct validity of the Thai EQ-5D was examined by specifying and testing hypotheses about the relationships between the EQ-5D, SF-36v2, and participants' demographic and medical characteristics. RESULTS: Construct validity of the Thai EQ-5D was supported by expected relationships with SF-36v2 scale and summary scores. For example, SF-36v2 scores on the mental health scale were much lower for participants who reported having problems on the EQ-5D anxiety/depression dimension compared to those reporting no problems (mean norm-based SF-36v2 scores: 52.9 vs. 41.8, p < 0.001). Additionally, reporting a problem in a given EQ-5D dimension was generally associated with lower SF-36v2 summary scores. The EQ-5D index score distinguished between groups of participants in the expected manner, on the basis of sex, age, education and self-reported health, thus providing evidence of known-groups validity. CONCLUSION: The study demonstrated good construct validity of the Thai EQ-5D in a large occupational population in Thailand.

The risk factors of low birth weight infants in the northern part of Thailand.

BACKGROUND: The incidence of low birth weight (LBW) in Chiang Mai University Hospital was high. OBJECTIVE: Determined the incidence and risk factors of low birth weight infants. MATERIAL AND METHOD: The present study included pregnant women between 1989 and 1990 who attended the antenatal clinics (ANC) having a gestational age less than or equal to 24 weeks. During that period, up to delivery, clinical and other potential data namely demographic and biomedical factors, maternal status, socioeconomic factors, and nutritional factors were included. The birth weight at birth less than 2,500 gm was considered LBW. RESULTS: Two thousand one hundred eighty four pregnant subjects who delivered live born and were still eligible, were used for analysis in the present study. The incidence of LBW was 9.2% (201/2,184). Women with body mass index (BMI) at first antenatal clinics (ANC) less than 18.5 Kg/m2 and weight gain during the second trimester less than 300 grams/week was the strongest independent risk factor for LBW (odds ratio 11.25, 95% confidence interval (CI) 5.77-21.94). The number of antenatal care less than 4, monilial vaginitis, the infestation of hookworm and strongyloides, and pregnancy-induced hypertension were independent risk factors (odds ratio 11.04, 3.14, 4.93 and 4.02 respectively). CONCLUSION: The present study showed that low initial BMI, low weight gain in the second trimester, and low attendance at ANC are associated to the occurrence of LBW. The development of a scoring system for detecting high-risk of LBW in pregnant women based on a combination of antenatal factors should be pursued.

Long-term effects of socioeconomic status on incident hypertension and progression of blood pressure.

OBJECTIVE: Few data have linked socioeconomic status (SES) to incident hypertension, and little information on the relationship between SES and hypertension are available from developing countries. We thus investigated the long-term effects of SES on incident hypertension and changes in blood pressure in Thailand. METHODS: In 1985, baseline data were collected from 3499 participants in the Electricity Generating Authority of Thailand study. Participants were re-examined in 1997, 2002 and 2007. Logistic regression models, Cox-proportional hazard models and time-dependent covariates were used to calculate the relationship between SES and prevalent hypertension in 1985, incident hypertension in 1997 and 2007, respectively. RESULTS: The prevalence of hypertension was 20% and the level of income, but not education, was inversely related to prevalent hypertension. Adjusting for several risk factors, compared to those who had tertiary education, participants who had primary education had 30% increased risk of incident hypertension in 1997 [hazard ratio 1.30, 95% confidence interval (CI) 1.09-1.54] and 20% in 2007 (1.20, 1.05-1.37); both P for trend was less than 0.01. Participants who had higher education also had substantially lower increments in SBP and DBP across 22 years (P < 0.0001 for SBP and P = 0.015 for DBP). Level of income was similarly negatively related to the progression of SBP, with a 3.6 mmHg difference between the highest income group and the lowest (P < 0.0001). CONCLUSION: Hypertensive counseling and surveillance should be emphasized within socioeconomically disadvantaged populations.

Lipid treatment assessment project II in Thailand (LTAP-II Thailand).

OBJECTIVE: Evaluate treatment practices and their outcomes in Thai patients with hyperlipidemia. The factors contributing to success of treatment were also determined. MATERIAL AND METHOD: A multi-center cross-sectional survey with the support of 98 physicians from 48 hospitals was done. Each physician enrolled up to 20 dyslipidemic patients by simple randomization. RESULTS: One thousand nine hundred twenty one cases, 45.1% males with a mean age of 58.6 years (SD = 9.6) were recruited. The patients were divided into three groups: 1,178 patients with coronary heart disease (CHD) and CHD equivalents, 424 patients with high risk, and 319 patients with low risk. The main targets for treatment were LDL-C levels of< 100, < 130 and < 160 mg/dL for each respective group. As a whole, the risk factors listed in order of frequency were age at risk (78%), hypertension (69. 8%), diabetes mellitus (43.6%), smoking (24.6%), and family history of CHD (6.9%). Obesity (body mass index > or = 25 kg/m2) was found in 53.8% of the patients. Twenty eight percent of the patients experienced CHD or other atherosclerotic diseases. Statin was the commonest prescribed drug (64%) followed by fibrate (25%). The overall success rate was 46.5%. Percentage of cases achieving LDL-C targets in the CHD and CHD equivalents, high and low risk group was 34.6%, 56.4%, and 76.8%, respectively. The patients in the low risk group, being under specialist care and receiving statin therapy reached target of treatment at a significantly higher rate. CONCLUSION: The present study showed that statin was the most common drug used in the management of hyperlipidemia. Patients with CHD and CHD equivalents were the group with least achievement of LDL-C target. The factors contributing to achievement of LDL-C target were lower risk patient, specialist care, and statin therapy.

Costs of payment in Thai acute coronary syndrome patients.

BACKGROUND: Acute coronary syndrome (ACS) is a major health care syndrome that can financially burden patients throughout the world, including Thailand. Few studies purposed estimating the costs of treatment. The data from the ACS registry database represented the costs of hospital charges paid by ACS patients. Although these were not the actual treatment costs, the authors can approximately estimate the total expenditure for the first admission. OBJECTIVES: First, calculate the cost of ACS to the patients, including diagnostic, demographic data, treatment modalities, type of payers, hospital profile, and outcomes. Second, find the appropriate model to identify the independent factors for predicting the treatment costs. MATERIAL AND METHOD: The present study collected data from the second and third phase of a national multicenter prospective registry of ACS in Thailand, Thai ACS registry (TACSR). 3,552 patients with new onset of ACS were analyzed. RESULTS: Median age was 67 years (range 26.5-105.5) with predominately male and median length of stay (LOS) was 7 days (range, 1-184). 42% referred from other hospitals. The median cost of the total population was 47,908 baht (range, 633-1,279,679). When classified into those of STEMI, NSTEMI, and UA, the costs were 82,848.5, 40,531 and 26,116 baht respectively, p < 0.0001. Patients in the government hospital had to pay the total cost with PCI and CABG, 152,081-161,374 baht and 203,139-223,747 baht respectively, while the private hospital charged almost twice as much. For the types of payers, private insurance including private employee security fund paid significantly more than others. Costs in patients paid by "30 baht na tional health scheme and social security fund" were significantly less than those of others. For modality of treatment in STEMI, primary PCI was significantly more costly than thrombolytics and no reperfusion therapy, 161,096.5 vs. 60,043.0 and 33,335.0 baht respectively p < 0.0001. Early invasive groups in NSTEMI/UA had much higher median costs 145,794.0 baht when compared to those of the conservative group, 47,908 baht, p < 0.0001. Two multiple linear regression models according to the diagnostic group identified the independent factors for predicting cost. PCI, LOS, CABG, admission in a private hospital, Death, GPIIb/IlIa inhibitors use, major bleeding, coronary angiogram, thrombolytics use, age and diabetes were independent predictors for the cost in STEMI patients, R2 = 0.58. For those of NSTEMI/UA, the independent predictors for the cost were PCI, LOS, CABG, admission in a private hospital, death, GP IIb/IIIa inhibitors use, major bleeding, coronary angiogram, age, ventricular arrhythmia, CHF and referred patients, R2 =0.62. CONCLUSION: Costs in ACS patients were markedly different among diagnostic groups. The clinical risk factors were hospital type, type of payers, referred system, treatment procedures, drugs used and complications including outcome. Some of these factors could independently predict the costs.