Catastrophic costs incurred by tuberculosis affected households from Thailand's first national tuberculosis patient cost survey.

Tuberculosis (TB) causes an economic impact on the patients and their households. Although Thailand has expanded the national health benefit package for TB treatment, there was no data on out-of-pocket payments and income losses due to TB from patients and their household perspectives. This national TB patient cost survey was conducted to examine the TB-related economic burden, and assess the proportion of TB patients and their households facing catastrophic total costs because of TB disease. A cross-sectional TB patient cost survey was employed following WHO methods. Structured interviews with a paper-based questionnaire were conducted from October 2019 to July 2021. Both direct and indirect costs incurred from the patient and their household perspective were valued in 2021 and estimated throughout pre- and post-TB diagnosis episodes. We assessed the proportion of TB-affected households facing costs > 20% of household expenditure due to TB. We analyzed 1400 patients including 1382 TB (first-line treatment) and 18 drug-resistant TB patients (DR-TB). The mean total costs per TB episode for all study participants were 903 USD (95% confident interval; CI 771-1034 USD). Of these, total direct non-medical costs were the highest costs (mean, 402 USD, and 95%CI 334-470 USD) incurred per TB-affected household followed by total indirect costs (mean, 393 USD, and 95%CI 315-472 USD) and total direct medical costs (mean, 107 USD, and 95%CI 81-133 USD, respectively. The proportion of TB-affected households facing catastrophic costs was 29.5% (95%CI 25.1-34.0%) for TB (first-line), 61.1% (95%CI 29.6-88.1%) for DR-TB and 29.9% (95%CI 25.6-34.4%) overall. This first national survey highlighted the economic burden on TB-affected households. Travel, food/nutritional supplementation, and indirect costs contribute to a high proportion of catastrophic total costs. These suggest the need to enhance financial and social protection mechanisms to mitigate the financial burden of TB-affected households.

Lifetime costs of alcohol consumption in Thailand: protocol for an incidence-based cost-of-illness study using Markov model.

INTRODUCTION: Several prevalence-based cost-of-illness (COI) studies have been conducted to estimate the economic burden of alcohol consumption borne by a particular society in a given year. Yet there are few studies examining the economic costs incurred by an individual drinker over his/her lifetime. Thus, this study aims to estimate the costs incurred by an individual drinker's alcohol consumption over his or her lifetime in Thailand. METHODS AND ANALYSIS: An incidence-based COI approach will be employed. To project individuals' associated costs over a lifetime, a Markov modelling technique will be used. The following six alcohol-related diseases/conditions will be considered in the model: hypertension, haemorrhagic stroke, liver cirrhosis, liver cancer, alcohol use disorders and road injury. The analysis will cover both direct (ie, direct healthcare cost, costs of property damage due to road traffic accidents) and indirect costs (ie, productivity loss due to premature mortality and hospital-related absenteeism). The human capital approach will be adopted to estimate the cost of productivity loss. All costs will be presented in Thai baht, 2022. ETHICS AND DISSEMINATION: The Institutional Review Board of Mahidol University, Faculty of Dentistry/Faculty of Pharmacy has confirmed that no ethical approval is required (COE.No.MU-DT/PY-IRB 2021/010.0605). Dissemination of the study findings will be carried out through peer-reviewed publications, conferences and engagement with policy-makers and public health stakeholders.

Economic costs of obesity: a systematic review.

INTRODUCTION: Obesity is a growing public health problem leading to substantial economic impact. This study aimed to summarize the economic impact of obesity and to critically analyze the methods used in the cost-of-illness (COI) studies on obesity. METHODS: We conducted systematic search in PubMed and Scopus from September 1, 2016, to July 22, 2022. Original COI studies estimating the economic cost of obesity and/or overweight in at least one country, published in English were included. To facilitate the comparison of estimates across countries, we converted the cost estimates of different years to 2022 purchasing power parity (PPP) values using each country's consumer price index (CPI) and PPP conversion rate. RESULTS: Nineteen studies were included. All studies employed a prevalence-based approach using Population Attributable Fraction (PAF) methodology. About half of the included studies (53%) were conducted in high-income countries while the others (47%) were conducted in middle-income countries. The economic burden of obesity ranged between PPP 15 million in Brazil to PPP 126 billion in the USA, in the year 2022. Direct medical costs accounted for 0.7% to 17.8% of the health system expenditure. Furthermore, the total costs of obesity ranged from 0.05% to 2.42% of the country's gross domestic product (GDP). Of the seven studies that estimated both direct and indirect costs, indirect costs accounted for the largest portion of five studies. Nevertheless, a variety in methodology across studies was identified. The number of co-morbidities included in the analysis varied across studies. CONCLUSIONS: Although there was a variety of methodologies across studies, consistent evidence indicated that the economic burden of obesity was substantial. Obesity prevention and control should be a public health priority, especially among countries with high prevalence of obesity.

Systematic review of the impact of health care expenditure on health outcome measures: implications for cost-effectiveness thresholds.

OBJECTIVE: Empirical estimates of the impact of healthcare expenditure on health outcome measures may inform the cost-effectiveness threshold (CET) for guiding funding decisions. This study aims to systematically review studies that estimated this, summarize and compare the estimates by country income level. METHODS: We searched PubMed, Scopus, York Research database, and [anonymized] for Reviews and Dissemination database from inception to 1 August 2023. For inclusion, a study had to be an original article, estimating the impact of healthcare expenditure on health outcome measures at a country level, and presented estimates, in terms of cost per quality-adjusted life year (QALY) or disability-adjusted life year (DALY). RESULTS: We included 18 studies with 385 estimates. The median (range) estimates were PPP$ 11,224 (PPP$ 223 - PPP$ 288,816) per QALY gained and PPP$ 5,963 (PPP$ 71 - PPP$ 165,629) per DALY averted. As ratios of Gross Domestic Product per capita (GDPPC), these estimates were 0.376 (0.041-182.840) and 0.318 (0.004-37.315) times of GDPPC, respectively. CONCLUSIONS: The commonly used CET of GDPPC seems to be too high for all countries, but especially low-to-middle-income countries where the potential health losses from misallocation of the same money are greater. REGISTRATION: The review protocol was published and registered in PROSPERO (CRD42020147276).

Economic costs of alcohol consumption in Thailand, 2021.

BACKGROUND: Alcohol is one of the leading risk factors contributing to avoidable economic loss worldwide. Estimates from the economic cost of alcohol consumption studies play an important role in prioritizing healthcare resource use, supporting policy decisions, and justifying budgets for alcohol policy. This study aimed to estimate the economic burden associated with alcohol consumption in Thailand in 2021. METHODS: Prevalence-based cost of illness methodology was employed. The following costs were included in the analysis: healthcare costs; cost of law enforcement; cost of property damage due to road traffic accidents; cost of premature mortality; and cost of absenteeism from out-patient hospital visits and hospitalization. Human capital approach was adopted. All costs were presented in Thai baht, 2021. RESULTS: Alcohol consumption incurred a total estimated economic cost of 165,450.5 million baht, equivalent to 1.02% of Gross Domestic Product (GDP) and 2500 baht per capita. Cost of premature mortality was estimated at 157,918.7 million baht and accounted for the largest proportion of the total cost (95.45%). Healthcare cost was found to be the second highest share representing 4370.1 million baht (2.7% of the total cost). The number of premature death attributable to alcohol consumption in 2021 was estimated at 22,804. CONCLUSIONS: Alcohol continues to impose a substantial economic burden in Thailand. Enforcement of existing well-formulated alcohol control policies is urgently required to mitigate the economic impact of alcohol consumption in the country.

Economic cost of patients with trisomy 13, 18, and 21 in a tertiary hospital in Thailand.

The purpose of this study was to determine direct and indirect costs of patients with trisomy (T) 13, 18, and 21 in Thailand. Direct medical costs were obtained from Siriraj Informatics and Data Innovation Center (SiData+), Faculty of Medicine, Siriraj Hospital, and indirect costs were estimated using a human capital approach. About 241 patients with T21 had outpatient care visits and 124 patients received inpatient care. For T13 and T18, five and seven patients were analyzed for outpatient and inpatient cares, respectively. For patients with T13, T18, and T21 receiving outpatient care, total annual mean direct medical costs ranged from 183.2 USD to 655.2 USD. For inpatient care, average yearly direct medical costs varied between 2,507 USD to 14,790 USD. The mean and median increased with age. In outpatient care, costs associated with drugs and medical devices were a major factor for both T13 and T21 patients, whereas laboratory costs were substantial for T18 patients. For inpatient care, costs of drug and medical devices were the greatest for T13 patients, while service fee and operation costs were the highest for T18 and T21 patients, respectively. For outpatient care, adult patients with congenital heart disease (CHD) had significantly higher mean annual direct medical costs than those without CHD. However, all adult and pediatric patients with CHD receiving inpatient care had significantly higher costs. Patients with T13, T18, and T21 had relative lifetime costs of 22,715 USD, 11,924 USD, and 1,022,830 USD, respectively.

Rituximab for the treatment of relapsing-remitting multiple sclerosis in Thailand: an economic evaluation and budget impact analysis.

BACKGROUND: Multiple sclerosis is an inflammatory demyelination process in the central nervous system (CNS) causing neurological disability and poor quality of life. Currently, Thai Food and Drug Administration (FDA)-approved disease-modifying therapy is costly, and most patients with multiple sclerosis are ineligible for treatment in Thailand as previous studies have challenged its cost-effectiveness. Off-label use of rituximab is inexpensive and highly effective in treating multiple sclerosis, but evidence of its cost-effectiveness in Thailand is yet to be collected. METHODS: This study aimed to evaluate the cost-utility and budget impact of rituximab for multiple sclerosis treatment compared with best supportive care, the standard practice in Thailand to treat the disease. A Markov model with a one-month cycle length and lifetime horizon was applied to compare the costs and outcomes of rituximab and best supportive care based on a societal perspective. Accordingly, incremental cost-effectiveness ratios were estimated. Probabilistic and one-way sensitivity analyses were conducted to investigate parameter uncertainty. In addition, the Markov model was used to assess the 5-year budget impact from the government perspective. RESULTS: A rituximab biosimilar demonstrated higher effectiveness and lower associated costs, compared to best supportive care, with the highest probability of being cost-effective (96%). The probability of relapse was the most sensitive parameter according to the one-way sensitivity analysis. The calculated budget impact of treating patients with multiple sclerosis in Thailand was 26,360,000 Thai baht (THB) or 844,255 United States dollars (USD) in the first fiscal year, and approximately 20,810,000-23,080,000 THB (666,608-739,388 USD) in the next four fiscal years. CONCLUSION: In Thailand, a rituximab biosimilar would reduce the overall costs of multiple sclerosis treatment and should, therefore, be included in the National List of Essential Medicines.

Efficacy of anti-tuberculosis drugs for the treatment of latent tuberculosis infection: a systematic review and network meta-analysis.

Despite the availability of three network meta-analyses (NMA) examining the efficacy, treatment completion, and adverse events associated with all latent tuberculosis infection (LTBI) treatments, there is currently no evidence to support the notion that the benefits of these treatments outweigh the potential risks. This NMA aimed to conduct a comprehensive comparison and update of the efficacy, treatment completion rates and adverse events associated with recommended treatment options for LTBI for individuals with confirmed LTBI, as outlined in the 2020 World Health Organization (WHO) Consolidated Guidelines for TB preventive treatment. A comprehensive search of the MEDLINE and Scopus databases was conducted until April 2023. The NMA was applied to estimate the risk difference and corresponding 95% confidence interval (CI) using a combination of direct and indirect evidence. The risk-benefit assessment was employed to evaluate the feasibility of the extra benefits in relation to the extra risks. The primary outcomes of interest in this study were active TB disease, completion rates, and adverse events. The meta-analysis incorporated data from 15 studies, which collectively demonstrated that the administration of a placebo resulted in a significant increase in the risk of developing TB disease by 1.279%, compared to the daily intake of isoniazid for 6 months (6H). Furthermore, treatment completion rates were significantly higher when using isoniazid plus rifapentine weekly for 3 months (3HP) and rifampicin daily for 4 months (4R), as compared to 6H. Considering adverse events, the combination of 3HP, 4R, and isoniazid administered daily for 9 months (referred to as 9H) significantly decreased adverse events by 4.53% in comparison to 6H. The risk-benefit assessment showed that alternative treatment regimens (9H, 4R, 3HR and 3HP) had a lower incidence of adverse events, while demonstrating a higher efficacy in preventing TB, as compared to 6H. This review indicates that there were no significant differences observed among various active treatment options in terms of their efficacy in preventing active TB. Moreover, completion rates were higher in 3HP and 4R, and a reduction in adverse events was observed in 3HP, 4R, and 9H.

Effect of vitamin D supplementation on circulating level of autophagosome protein LC3A, inflammation, and physical performance in knee osteoarthritis.

Aberrant autophagic activity is observed in osteoarthritic joints. Vitamin D was shown to alleviate not only osteoarthritis severity, but also autophagy process. However, the influence of vitamin D on autophagy in knee osteoarthritis (KOA) remains ambiguous. This study aimed to determine the effect of vitamin D2 on serum levels of autophagosome protein LC3A in patients with KOA and whether LC3A levels were correlated with serum 25-hydroxyvitamin D (25(OH)D) and clinical outcomes of patients with KOA. A total of 165 patients with KOA and 25 healthy controls were recruited. Vitamin D2 (ergocalciferol) was administered to patients with KOA at a weekly dosage of 40,000 IU. Serum LC3A, knee pain and functional scores, muscle strength, physical performance, and biochemical parameters were examined before and after 6 months of vitamin D2 supplementation. Serum LC3A levels were significantly higher in patients with KOA than healthy controls. In patients with KOA, vitamin D2 supplementation significantly decreased serum LC3A levels. Furthermore, baseline levels of serum LC3A were significantly associated with radiographic severity, pain and functional scores, total cholesterol, hs-CRP, IL-6, protein carbonyl, and serum 25(OH)D. After adjusting for established confounders, independent relationships among serum LC3A and radiographic severity, pain and functional scores, total cholesterol, hs-CRP, IL-6, protein carbonyl, and serum 25(OH)D were also observed. Vitamin D2 supplementation was shown to not only decrease serum levels of LC3A, inflammatory markers, as well as oxidative stress, but also improve muscle strength and physical performance in patients with KOA.

Economic evaluation of prenatal screening for fetal aneuploidies in Thailand.

Historically, there has been a lack of cost-effectiveness data regarding the inclusion of universal non-invasive prenatal testing (NIPT) for trisomy 21, 18, and 13 in the benefit package of the Universal Health Coverage (UHC) in Thailand. Therefore, this study aimed to perform the cost-benefit analysis of prenatal screening tests and calculate the budget impact that would result from the implementation of a universal NIPT program. A decision-tree model was employed to evaluate cost and benefit of different prenatal chromosomal abnormalities screenings: 1) first-trimester screening (FTS), 2) NIPT, and 3) definitive diagnostic (amniocentesis). The comparison was made between these screenings and no screening in three groups of pregnant women: all ages, < 35 years, and ≥ 35 years. The analysis was conducted from societal and governmental perspectives. The costs comprised direct medical, direct non-medical, and indirect costs, while the benefit was cost-avoidance associated with caring for children with trisomy and the loss of productivity for caregivers. Parameter uncertainties were evaluated through one-way and probabilistic sensitivity analyses. From a governmental perspective, all three methods were found to be cost-beneficial. Among them, FTS was identified as the most cost-beneficial, especially for pregnant women aged ≥ 35 years. From a societal perspective, the definitive diagnostic test was not cost-effective, but the other two screening tests were. The most sensitive parameters for FTS and NIPT strategies were the productivity loss of caregivers and the incidence of trisomy 21. Our study suggested that NIPT was the most cost-effective strategy in Thailand, if the cost was reduced to 47 USD. This evidence-based information can serve as a crucial resource for policymakers when making informed decisions regarding the allocation of resources for prenatal care in Thailand and similar context.

Host genetic polymorphisms involved in long-term symptoms of COVID-19.

Host genetic polymorphisms are recognized as a critical determinant of diversity in clinical symptoms of Coronavirus disease 2019 (COVID-19). Accordingly, this study aimed to determine possible associations between single nucleotide polymorphisms (SNPs) in 37 candidate genetic variants and clinical consequences of COVID-19 - especially long-term symptoms, Long COVID. A total of 260 COVID-19 patients, divided into mild (n = 239) and severe (n = 21) and further categorized based on the presence of Long COVID (no, n = 211; yes, n = 49), were recruited. Genotyping of selected polymorphisms responsible for viral entry, immune response, and inflammation was performed using MassARRAY system. Out of 37 SNPs, 9 including leucine zipper transcription factor like-1 (LZTFL1) rs10490770 C allele, LZTFL1 rs11385942 dupA allele, nicotinamide adenine dinucleotide synthetase-1 (NADSYN1) rs12785878 TT genotype, plexin A-4 (PLXNA4) rs1424597 AA genotype, LZTFL1 rs17713054 A allele, interleukin-10 (IL10) rs1800896 TC genotype and C allele, angiotensin converting enzyme-2 (ACE2) rs2285666 T allele, and plasmanylethanolamine desaturase-1 (PEDS1) rs6020298 GG genotype and G allele were significantly associated with an increased risk of developing Long COVID, whereas interleukin-10 receptor subunit beta (IL10RB) rs8178562 GG genotype was significantly associated with a reduced risk of Long COVID. Kaplan-Meier curve displayed that the above gene polymorphisms were significantly associated with cumulative rate of Long COVID occurrence. Polymorphisms in LZTFL1 rs10490770, LZTFL1 rs11385942, LZTFL1 rs17713054, NADSYN1 rs12785878, PLXNA4 rs1424597, IL10 rs1800896, ACE2 rs2285666, PEDS1 rs6020298, and IL10RB rs8178562 appear to be genetic factors involved in development of Long COVID.

Prenatal screening tests and prevalence of fetal aneuploidies in a tertiary hospital in Thailand.

This study evaluated prenatal screening test performance and the prevalence of common aneuploidies at Siriraj Hospital, Thailand. We collected data from screening tests which are first-trimester test, quadruple test, and noninvasive prenatal tests (NIPT) between January 2016 and December 2020. Thirty percent (7,860/25,736) of pregnancies received prenatal screening tests for aneuploidies disorders, and 17.8% underwent prenatal diagnosis tests without screening. The highest percentage of screening tests was first-trimester test (64.5%). The high-risk results were 4% for first-trimester test, 6.6% for quadruple test, and 1.3% for NIPT. The serum screening tests for trisomy 13 and 18 had no true positives; therefore, we could not calculate sensitivity. For the first-trimester test, the sensitivity for trisomy 21 was 71.4% (95% confidence intervals (CI) 30.3-94.9); specificity for trisomy 13 and 18 was 99.9% (95% CI 99.8-99.9); and for trisomy 21 was 96.1% (95% CI 95.6-96.7). For the quadruple test, the specificity for trisomy 18 was 99.6% (95% CI 98.9-99.8), while the sensitivity and specificity for trisomy 21 were 50% (95% CI 26.7-97.3) and 93.9% (95% CI 92.2-95.3), respectively. NIPT had 100% sensitivity and specificity for trisomy 13, 18 and 21, and there were neither false negatives nor false positives. For pregnant women < 35 years, the prevalence of trisomy 13, 18, and 21 per 1,000 births was 0.28 (95% CI 0.12-0.67), 0.28 (95% CI 0.12-0.67), and 0.89 (95% CI 0.54-1.45), respectively. For pregnant women ≥35 years, the prevalence of trisomy 13, 18, and 21 per 1,000 births was 0.26 (95% CI 0.06-1.03), 2.59 (95% CI 1.67-4.01), and 7.25 (95% CI 5.58-9.41), respectively. For all pregnancies, the prevalence of trisomy 13, 18, and 21 per 1,000 births was 0.27 (95% CI 0.13-0.57), 0.97 (95% CI 0.66-1.44), 2.80 (95% CI 2.22-3.52), respectively.

Efficacy and safety of monoclonal antibody therapy in patients with neuromyelitis optica spectrum disorder: A systematic review and network meta-analysis.

Introduction: Neuromyelitis optica spectrum disorder (NMOSD) is a devastating inflammatory CNS demyelinating disease. Two groups of monoclonal antibodies (mAbs) are used to prevent disease relapse, i.e., Food and Drug Administration (FDA)-approved mAbs (e.g., eculizumab satralizumab, inebilizumab), and off-label mAb drugs (e.g., rituximab and tocilizumab). The FDA-approved mAbs have high efficacy but more expensive compared to the off-labels, and thus are less accessible. This systematic review and network meta-analysis (NMA) was to assess the efficacy and safety of both classes of mAbs compared to the current standard treatments. Methods: Systematically searches were conducted in MEDLINE and SCOPUS from inception until July 2021. Randomized-controlled trials (RCTs) were eligible if they compared any pair of treatments (mAbs, immunosuppressive drugs, or placebo) in adult patients with NMOSD. Studies with AQP4-IgG positive or negative were used in the analysis. Probability of relapse and time to event were extracted from the Kaplan-Meier curves using Digitizer. These data were then converted into individual patient time-to-event data. A one-stage mixed-effect survival model was applied to estimate the median time to relapse and relative treatment effects using hazard ratios (HR). Two-stage NMA was used to determine post-treatment annualized relapse rate (ARR), expanded disability status score (EDSS) change, and serious adverse events (SAE). Risk of bias was assessed using the revised cochrane risk of bias tool. Results: A total of 7 RCTs with 776 patients were eligible in the NMA. Five of the seven studies were rated low risk of bias. Both FDA-approved and off-label mAbs showed significantly lower risk of relapse than standard treatments, with HR (95% CI) of 0.13 (0.07, 0.24) and 0.16 (0.07, 0.37) respectively. In addition, the FDA-approved mAbs had 20% lower risk of relapse than the off-label mAbs, but this did not reach statistical significance. The ARRs were also lower in FDA-approved and off-label mAbs than the standard treatments with the mean-difference of-0.27 (-0.37,-0.16) and-0.31(-0.46,-0.16), respectively. Conclusion: The off-label mAbs may be used as the first-line treatment for improving clinical outcomes including disease relapse, ARR, and SAEs for NMOSD in countries where resources and accessibility of the FDA-approved mAbs are limited. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=283424, identifier: CRD42021283424.

Comparative cardiovascular benefits of individual SGLT2 inhibitors in type 2 diabetes and heart failure: a systematic review and network meta-analysis of randomized controlled trials.

Background: In patients with type 2 diabetes (T2D) and a history of heart failure (HF), sodium-glucose cotransporter-2 inhibitors (SGLT2is) have demonstrated cardiovascular (CV) benefits. However, the comparative efficacy of individual SGLT2is remains uncertain. This network meta-analysis (NMA) compared the efficacy and safety of five SGLT2is (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, and sotagliflozin) on CV outcomes in these patients. Materials and methods: PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched up to September 23, 2022, to identify all randomized controlled trials (RCTs) comparing SGLT2is to placebo in T2D patients with HF. The main outcomes included composite CV death/heart failure hospitalization (HFH), HFH, CV death, all-cause mortality, and adverse events. Pairwise and NMA approaches were applied. Results: Our analysis included 11 RCTs with a total of 20,438 patients with T2D and HF. All SGLT2is significantly reduced HFH compared to standard of care (SoC) alone. "Add-on" SGLT2is, except ertugliflozin, significantly reduced composite CV death/HFH relative to SoC alone. Moreover, canagliflozin had lower composite CV death/HFH compared to dapagliflozin. Based on the surface under the cumulative ranking curve (SUCRA), the top-ranked SGLT2is for reducing HFH were canagliflozin (95.5%), sotagliflozin (66.0%), and empagliflozin (57.2%). Head-to-head comparisons found no significant differences between individual SGLT2is in reducing CV death. "Add-on" SGLT2is reduced all-cause mortality compared with SoC alone, although only dapagliflozin was statistically significant. No SGLT2is were significantly associated with serious adverse events. A sensitivity analysis focusing on HF-specific trials found that dapagliflozin, empagliflozin, and sotagliflozin significantly reduced composite CV death/HFH, consistent with the main analysis. However, no significant differences were identified from their head-to-head comparisons in the NMA. The SUCRA indicated that sotagliflozin had the highest probability of reducing composite CV death/HFH (97.6%), followed by empagliflozin (58.4%) and dapagliflozin (44.0%). Conclusion: SGLT2is significantly reduce the composite CV death/HFH outcome. Among them, canagliflozin may be considered the preferred treatment for patients with diabetes and a history of heart failure, but it may also be associated with an increased risk of any adverse events compared to other SGLT2is. However, a sensitivity analysis focusing on HF-specific trials identified sotagliflozin as the most likely agent to reduce CV death/HFH, followed by empagliflozin and dapagliflozin. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022353754.

Economic Evaluation of Screening Strategy for Latent Tuberculosis Infection (LTBI) in Contacts of Tuberculosis Patients: Systematic Review and Quality Assessment.

A tuberculin skin test (TST) or interferon-gamma release assay (IGRA) can be used to screen for latent tuberculosis infection (LTBI). Due to its low cost, TST has been used particularly in underdeveloped countries. The limitations of TST were poor specificity in populations with a high prevalence of Bacille Calmette-Guérin (BCG) vaccination and variability of test readers. IGRA is used as an alternative to TST in settings where higher costs can be supported. The lack of studies conducted in high TB incidence countries since previous review, and using relevant assessment tools of the quality appraisal make the need for updated studies and a more comprehensive systematic review. This study aimed to conduct a systematic review of published economic evaluations of screening strategies for LTBI in contacts of TB patients, assess the quality of these studies, and compare the assessment results related to a country's income level in order to provide information to other countries. The databases were searched in January 2022 including MEDLINE and Scopus. Two independent reviewers evaluated the included studies based on eligibility criteria, data extraction, and quality assessment. Eleven economic evaluations of LTBI diagnostic tests in TB contacts were included. Most studies were conducted in high-income countries (91%) and used cost-effectiveness analysis methods (73%). The quality assessment of reporting and data sources was appropriate, ranging from 71% to 89%. Interventions varied from study to study. The outcomes were cost per life years gained (27%), cost per quality-adjusted life year gained (27%), cost per TB case prevented (36%), and cost per close contact case (10%). In high-income countries which were not countries with high TB burden, the use of IGRA alone for screening TB contacts was cost-effective, whereas TST was cost-effective in only two studies. In comparison to TST, IGRA could reduce false-positive results, resulting in fewer patients undergoing TB treatment and preventive treatment.

Mitochondrial DNA content as a diagnostic marker for antituberculosis drug-induced liver injury.

OBJECTIVES: This study aimed to investigate whether mitochondrial DNA (mtDNA) content, an index of mitochondrial dysfunction, was associated with clinical parameters indicating anti-tuberculosis (TB) drug-induced liver injury (ATDILI) in TB patients and could emerge as an ATDILI biomarker. METHODS: Leukocyte mtDNA content in 102 TB patients (49 ATDILI cases and 53 non-ATDILI cases) and 100 age-matched healthy controls was measured using real-time polymerase chain reaction. RESULTS: Compared with healthy controls, both TB patients with and without ATDILI had significantly decreased mtDNA content. Compared with the patients without ATDILI, mtDNA content was significantly increased in those with ATDILI. Higher mtDNA content was observed to be independently associated with increased susceptibility to ATDILI. Increased mtDNA content measured within 1-7 days of treatment was independently associated with elevated levels of serum aminotransferases assessed within 8-60 days of treatment. After initiating treatment within 1-7 days, mtDNA content was detected to be more sensitive and selective for differentiating TB patients with ATDILI from those without ATDILI than serum aminotransferases. Kaplan-Meier analysis revealed a significant correlation between elevated mtDNA content and increased rate of ATDILI occurrence in TB patients, attested by Cox regression analysis, adjusting for confounders. CONCLUSION: Changes in leukocyte mtDNA content would reflect ATDILI progression and could be used as a potential stratification tool for identifying TB patients at risk of ATDILI.

Economic Evaluation of Multiple-Pharmacogenes Testing for the Prevention of Adverse Drug Reactions in People Living with HIV.

Purpose: Pharmacogenetics (PGx) testing is one of the methods for determining whether individuals are at risk of adverse drug reactions (ADRs). It has been reported that multiple-PGx testing, a sequencing technology, has a higher predictive value than single-PGx testing. Therefore, this study aimed to determine the most cost-effective PGx testing strategies for preventing drug-induced serious ADRs in human immunodeficiency virus (HIV)-infected patients. Patients and Methods: Potential strategies, including 1) single-PGx esting (ie, HLA-B*57:01 testing before prescribing abacavir, HLA-B*13:01 testing before prescribing co-trimoxazole and dapsone, and NAT2 testing before prescribing isoniazid) and 2) multiple-PGx testing as a combination of four single-gene PGx tests in one panel, were all compared to no PGx testing (current practice). To evaluate total cost in Thai baht (THB) and quality-adjusted life years (QALYs) for each strategy-based approach to a societal perspective, a hybrid decision tree and Markov model was constructed. Incremental cost-effectiveness ratios (ICERs) were estimated. Uncertainty, threshold, and scenario analyses were all performed. Results: Before prescribing HIV therapy, providing single or multiple-PGx testing might save roughly 68 serious ADRs per year, and the number needed to screen (NNS) to avoid one serious ADR was 40. Consequently, approximately 35% and 40% of the cost of ADR treatment could be avoided by the implementation of single- and multiple-PGx testing, respectively. Compared with no PGx testing strategy, the ICERs were 146,319 THB/QALY gained for single-PGx testing and 152,014 THB/QALY gained for multiple-PGx testing. Moreover, the probability of multiple-PGx testing being cost-effective was 45% at the Thai willingness to pay threshold of 160,000 THB per QALY. Threshold analyses showed that multiple-PGx testing remained cost-effective under the range of cost, sensitivity at 0.95-1.00 and specificity at 0.98-1.00. Conclusion: Single and multiple-PGx testing might be cost-effective options for reducing the incidence of drug-induced serious ADRs in people living with HIV.

The Association of HLA-B*35 and GSTT1 Genotypes and Hepatotoxicity in Thai People Living with HIV.

Glutathione s-transferase (GST) is a family of drug-metabolizing enzymes responsible for metabolizing and detoxifying drugs and xenobiotic substances. Therefore, deletion polymorphisms of GSTs can be implicated in developing several pathological conditions, including antiretroviral drug-induced liver injury (ARVDILI). Notably, GST polymorphisms have been shown to be associated with ARVDILI risk. However, data on GST polymorphisms in the Thai population are limited. Therefore, this study investigated possible associations between GST genetic polymorphisms and ARVDILI development. A total of 362 people living with HIV (PLHIV) and 85 healthy controls from multiple centers were enrolled. GSTM1 and GSTT1 genetic polymorphisms were determined using polymerase chain reactions. In addition, HLA genotypes were determined using a sequence-based HLA typing method. After comparing GST genotypic frequencies, there was no significant difference between PLHIV and healthy volunteers. However, while observing the PLHIV group, GSTT1 wild type was significantly associated with a 2.04-fold increased risk of ARVDILI (95%CI: 1.01, 4.14; p = 0.045). Interestingly, a combination of GSTT1 wild type and HLA-B*35:05 was associated with a 2.28-fold higher risk of ARVDILI (95%CI: 1.15, 4.50; p = 0.02). Collectively, GSTT1 wild type and a combination of GSTT1 wild type plus HLA-B*35:05 were associated with susceptibility to ARVDILI in the Thai population.

Incremental net monetary benefit of direct oral anticoagulants for the prevention of venous thromboembolism after total knee or hip replacement: A systematic review and meta-analysis.

INTRODUCTION: This meta-analysis was conducted to quantitatively pool the incremental net benefit (INB) of using direct oral anticoagulants (DOACs) for the prevention of venous thromboembolism (VTE) in patients undergoing total knee or hip replacements (TKR or THR). MATERIALS AND METHODS: We performed a comprehensive search in several databases published before June 2021. Studies were included if they were cost-effectiveness analyses reporting cost per quality-adjusted life-year or life-year of DOACs compared to low molecular-weight heparins (LMWHs) or other anticoagulant agents for the prevention of VTE after TKR or THR. Risk of bias was also assessed using the biases in economic studies (ECOBIAS) checklist. Various monetary units were converted to purchasing power parity, adjusted to 2020 US dollars. The INBs were pooled across studies using a random-effects model, stratified by high-income countries (HICs) and low- and middle-income countries (LMICs). Heterogeneity was assessed using the I2 statistic. RESULTS: A total of 49 comparisons (TKR = 25 and THR = 24) from 16 studies was included. In HICs, DOACs were cost-effective compared to LMWHs from the health care system/payer perspective for the prevention of VTE after both TKR and THR with corresponding INBs (95 % CI; I2) of $231.91 ($178.71, $285.11; 0 %) and $254.99 ($159.20, $350.77; 27.79 %), respectively. In LMICs, DOACs were not cost-effective compared to LMWHs for both TKR and THR with the INBs of $94.13 (-$40.21, $228.47; 97.04 %) and $80.55 (-$157.37, $318.47; 99.78 %), respectively. No evidence of small-study effects was identified in any analyses. The cost-effectiveness of using DOACs for TKR and THR in HICs was robust across a series of sensitivity analyses. CONCLUSIONS: DOACs were cost-effective as compared to LMWHs for VTE prophylaxis following TKR and THR surgeries in HICs. Further studies from LMICs are warranted.

Comparative efficacy and safety of pharmacologic interventions to prevent mother-to-child transmission of hepatitis B virus: a systematic review and network meta-analysis.

OBJECTIVE: This study investigated the efficacy and safety of pharmacologic interventions to prevent vertical transmission of the hepatitis B virus. DATA SOURCES: Medline, Cochrane, and Scopus databases were searched up to October 28, 2020. STUDY ELIGIBILITY CRITERIA: All randomized controlled trials reporting vertical hepatitis B virus transmission with pharmacologic intervention were included. METHODS: Risk of bias was assessed using the Cochrane Risk-of-Bias tool, version 2. Treatment efficacy was estimated using stratified network meta-analysis on the basis of maternal hepatitis B envelope antigen status. RESULTS: Nineteen studies were included for mothers positive for hepatitis B surface and envelope antigens. Pooling indicated that a combination of hepatitis B vaccination and hepatitis B immunoglobulin in infants significantly reduced transmission risk compared with vaccination alone, with a risk ratio of 0.52 (95% confidence interval; 0.30-0.91). Only the addition of maternal tenofovir disoproxil fumarate, but not telbivudine, lamivudine, or maternal hepatitis B immunoglobulin further reduced transmission risk compared with a combination of hepatitis B vaccination and hepatitis B immunoglobulin in infants, with a pooled risk ratio of 0.10 (0.03-0.35). Twelve studies conducted in mothers with hepatitis B surface antigen positivity and mixed, unknown, or negative hepatitis B envelope antigen status provided limited evidence to suggest that maternal hepatitis B immunoglobulin combined with hepatitis B vaccination and immunoglobulin in infants was the likely best treatment, but this failed to reach statistical significance compared with a combination of hepatitis B vaccination and immunoglobulin in infants. Similarly, infant hepatitis B immunoglobulin, added to vaccination, likely provides additional benefit but failed to reach statistical significance. CONCLUSION: A combination of hepatitis B vaccination and immunoglobulin in infants is the cornerstone for prevention of vertical transmission for mothers positive for both hepatitis B surface and envelope antigens. The addition of maternal tenofovir to this infant combination regimen was considered the likely most effective treatment. For infants of mothers with hepatitis B surface antigen positivity and mixed, unknown, or negative hepatitis B envelop antigen status, no additional agents provided further benefit beyond hepatitis B vaccination alone.