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PurposeCytokine storm, an uncontrolled overproduction of inflammatory cytokines contributing to an aberrant systemic inflammatory response, is a major pathological feature of acute respiratory distress syndromes being severe manifestations of COVID-19, thus highlighting its potential as a biomarker and therapeutic target for COVID-19. We aimed to determine associations of circulating levels of inflammatory cytokines with severity and mortality of COVID-19 by systematic review and meta-analysis.MethodsA comprehensive literature search in electronic databases consisting of PubMed, Scopus, and Cochrane Library and in a hand searching of reference lists from inception to July 31, 2020, was performed using the following search terms: COVID-19, interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha (TNF-α). Mean difference (MD) from individual studies was pooled using a random-effects model. Quality assessment, publication bias, meta-regression, subgroup, and sensitivity analyses were performed.ResultsA total of 6212 COVID-19 patients from 24 eligible studies were included. Compared with non-severe COVID-19 patients, systemic levels of IL-6 and IL-10, but not TNF-α, were significantly elevated in severe COVID-19 patients (MD = 18.63, 95% CI: 10.91, 26.35, P < 0.00001; MD = 2.61, 95% CI: 2.00, 2.32, P < 0.00001; respectively). For COVID-19 mortality, circulating levels of IL-6, IL-10, and TNF-α were found to be significantly increased in non-survivors when compared with survivors (MD = 57.82, 95% CI: 10.04, 105.59, P = 0.02; MD = 4.94, 95% CI: 3.89, 6.00, P < 0.00001; MD = 5.60, 95% CI: 4.03, 7.17, P < 0.00001; respectively).ConclusionCirculating levels of IL-6 and IL-10 might have great potential as biomarkers for the disease severity and mortality in COVID-19 patients.

Background: Although the body of evidence indicates clear benefits of dietary modifications for prevention of type-2 diabetes mellitus (T2DM), it may be difficult for healthcare providers to recommend which diet interventions or dietary factors are appropriate for patients as there are too many modalities available. Accordingly, we performed an umbrella review to synthesize evidence on diet interventions and dietary factors in prevention of T2DM. Methods: Medline and Scopus databases were searched for relevant studies. Systematic reviews with meta-analyses of randomized-controlled trial or observational studies were eligible if they measured effects of diet interventions and/or dietary factors including dietary patterns, food groups, and nutrients on risk of T2DM. The effect of each diet intervention/factor was summarized qualitatively. Results: Sixty systematic reviews and meta-analyses were eligible. Results of the review suggest that healthy dietary patterns such as Mediterranean and Dietary Approaches to Stop Hypertension (DASH) diets, and high consumption of whole grains, low-fat dairy products, yogurt, olive oil, chocolate, fiber, magnesium, and flavonoid significantly reduced the risk of T2DM. In contrast, high glycemic index and glycemic load diets, high consumption of red and processed meat, and sugar or artificial sugar-sweetened beverages significantly increased risk of T2DM. Prescribing diet interventions with or without physical activity interventions significantly decreased risk of T2DM in both high-risk and general population. Conclusion: High consumption of Mediterranean and DASH diet, and interventions that modified the quality of diet intake significantly reduced risk of T2DM especially in the high-risk population. These lifestyle modifications should be promoted in both individual and population levels to prevent and decrease burden from T2DM in the future.

Bevacizumab (BEV) combined with standard chemotherapy with carboplatin and paclitaxel (CP) as the front-line treatment for newly diagnosed advanced-stage epithelial ovarian cancer (EOC) is a promising treatment option. In Thailand, combined BEV and CP for patients with high-risk EOC is not yet covered. This study aimed to explore the cost-effectiveness of combined BEV and CP for subgroups with high-risk EOC. Cost-utility analysis was conducted to compare the effectiveness of CP alone versus combined BEV and CP according to the Gynecologic Oncology Group-218 (GOG-218) and the Gynecologic Cancer Intergroup International Collaboration on Ovarian Neoplasms 7 (ICON-7) regimens in patients with EOC. The decision tree model and Markov model were applied, and incremental cost-effectiveness ratios (ICERs) were analyzed. Data on direct medical costs were obtained from cost databases in Thailand. Details about all clinical parameters and direct non-medical costs were obtained from published studies. Utility information was collected by interviewing patient subgroups with high-risk EOC. One-way and probabilistic sensitivity analyses were performed to evaluate parameter uncertainties. Based on the provider and societal perspectives, the ICERs of CP and the GOG-218 regimen were $31,266 and $31,966 per quality adjusted life year (QALY) gained, respectively. Meanwhile, the ICERs of CP and the ICON-7 regimen were $14,331 and $15,003 per QALY gained, respectively. The probabilities of cost-effectiveness for using BEV as the GOG-218 and ICON-7 regimens were 0% and 3%, respectively, based on the willingness-to-pay threshold in Thailand ($4,571 per QALY gained). The median progression-free survival of patients who received combined BEV and CP was the most important parameter leading to more benefit from using BEV. BEV as the GOG-218 or ICON-7 regimen may not be cost-effective for patient subgroups with high-risk EOC in Thailand. However, BEV as the ICON-7 regimen is more likely to be effective.

This systematic review aimed to comprehensively synthesize cost-effectiveness evidences of bariatric surgery by pooling incremental net monetary benefits (INB). Twenty-eight full economic evaluation studies comparing bariatric surgery with usual care were identified from five databases. In high-income countries (HICs), bariatric surgery was cost-effective among mixed obesity group (i.e., obesity with/without diabetes) over a 10-year time horizon (pooled INB = $53,063.69; 95% CI $42,647.96, $63,479.43) and lifetime horizon (pooled INB = $101,897.96; 95% CI $79,390.93, $124,404.99). All studies conducted among obese with diabetes reported that bariatric surgery was cost-effective. Also, the pooled INB for obesity with diabetes group over lifetime horizon in HICs was $80,826.28 (95% CI $32,500.75, $129,151.81). Nevertheless, no evidence is available in low- and middle-income countries.

Background In the context of ever-growing health expenditure and limited resources, economic evaluations aid in making evidence-informed policy decisions. Cost-utility analysis (CUA) is often used, and CUA data synthesis is also desirable, but methodological issues are challenged. Hence, we aim to provide a step-by-step process to prepare the CUA data for meta-analysis. Methods Data harmonisation methods were constructed specifically considering CUA methodology, including inconsistent reports, economic parameters, heterogeneity (i.e., country’s income, time horizon, perspective, modelling approaches, currency, willingness to pay). An incremental net benefit (INB) and its variance were estimated and pooled across studies using a basic meta-analysis by COMER. Results Five scenarios show how to obtain INB and variance with various reported data: Study reports the mean and variance (Scenario 1) or 95% confidence interval (Scenario 2) of ΔC, ΔE, and ICER for INB/variance calculations. Scenario 3: ΔC, ΔE, and variances are available, but not for the ICER; a Monte Carlo was used to simulate ΔC and ΔE data, variance and covariance can be then estimated leading INB calculation. Scenario-4: Only the CE plane was available, ΔC and ΔE data can be extracted; means of ΔC, ΔE, and variance/covariance can be estimated accordingly, leading to INB/variance estimates. Scenario-5: Only mean cost/outcomes and ICER are available but not for variance and the CE-plane. A variance INB can be borrowed from other studies which are similar characteristics, including country income, ICERs, intervention-comparator, time period, country region, and model type and inputs (i.e., discounting, time horizon). Conclusion Out data harmonisation and meta-analytic methods should be useful for researchers for the synthesis of economic evidence to aid policymakers in decision making.

Currently, due to the absence of economic evaluation information, automated peritoneal dialysis (APD) is not included in Thailand’s Universal Health Coverage (UHC) benefit package. Therefore, we aimed to assess the cost-utility and budget impact of APD and continuous ambulatory peritoneal dialysis (CAPD) in pediatric end-stage kidney disease (ESKD) patients. A Markov model was applied to compare lifetime costs and health outcomes based on a social perspective using cost, utility, and transitional probability data from literature reviews. The results were presented as the incremental cost-effectiveness ratio (ICER). Moreover, one-way and probabilistic sensitivity analyses were performed to evaluate the uncertainty of all parameters. From a social perspective, patients receiving APD had higher total lifetime cost (14,791,473 baht) than those receiving CAPD (13,380,356 baht), but fewer life years (APD = 18.39, CAPD = 18.44) and higher quality adjusted life years (QALY) (APD = 16.31 and CAPD 15.65). At the societal willingness to pay in Thailand equal to 160,000 baht per QALY gained, APD would not be cost-effective (ICER = 3,063,598 baht per QALY gained). The inclusion of APD can result in an increase in annual budget of 54 million baht. Therefore, this study would help inform policy decisions regarding the inclusion of APD for pediatric with ESKD in the UHC benefit package.

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.

Given the lack of cost-effectiveness information, continuous ambulatory peritoneal dialysis (CAPD) with icodextrin (CAPD+ICO) has not yet been included in the Universal Health Coverage (UHC) scheme. This study aimed to evaluate the cost-utility of dialysis treatments for end-stage renal disease (ESRD) patients with fluid and sodium overload, comparing CAPD+ICO and automated peritoneal dialysis (APD) against glucose-based CAPD. A Markov model was applied to evaluate lifetime costs and health outcomes from a societal perspective. Data, including transitional probabilities, direct medical and non-medical costs, and utilities, were collected from randomized controlled trials conducted across 16 hospitals in various regions of Thailand. Compared to glucose-based CAPD, the incremental cost-effectiveness ratio (ICER) for CAPD+ICO was 908,440 THB (26,082 USD) per quality-adjusted life year (QALY) gained, while APD was dominated, incurring higher costs and yielding fewer QALYs. The results indicated that glucose-based CAPD had a 90% probability of being the most cost-effective option from a societal perspective, based on Thailand’s willingness-to-pay (WTP) threshold of 160,000 THB (4,603 USD) per QALY gained. Therefore, CAPD+ICO is not considered a good value for money, requiring an additional annual budget of approximately 58 million THB (2 million USD). These findings provide important economic evaluation evidence to support policy decision-making alongside clinical effectiveness and equity considerations in guiding future UHC benefit package decisions for dialysis modalities among ESRD patients with fluid and sodium overload in Thailand.

This meta-analysis was conducted to determine the genotypic effects of rs4149056 and rs2306283 polymorphism in SLCO1B1 gene on myopathy in patients with statin. Studies were searched using multiple databases and selected following inclusion criteria. Two reviewers independently performed data extraction and assessments for risk of bias. Fixed-or-random-effect was applied to pool allele frequency/effects. Mixed-effect logit model was used to pool genotypic effects using individual patient data. Heterogeneity and publication bias were explored. Fourteen studies were pooled for rs4149056; the minor C allele frequency were 15% in Caucasians and 14% in Asians. Six studies were pooled for rs2306283; the minor G allele frequency was 34% in Caucasian and 75% in Asians. Genotypic effects of rs4149056 polymorphism in Caucasians indicated that statin users who carried CC and TC genotypes had a significantly higher risk of myopathy than those who carried TT genotype, with a pooled odds ratio (OR) of 2.9 (95% confidence interval, 1.59, 5.34) and 1.6 (1.20, 2.16), respectively. For subgroup analysis, CC and TC genotypes also suggested a higher risk of myopathy in simvastatin users [OR = 2.8 (1.17, 6.77) and OR = 1.8 (1.15, 2.77), respectively] and in atorvastatin users [OR = 4.0 (1.23, 12.63) and OR = 2.0 (1.11, 3.52), respectively] than those who carried TT genotype. There was no significant association between rs2306283 polymorphism and myopathy in Caucasians and Asians. There was no evidence of publication bias for both polymorphisms.

This study aimed to determine whether promoter methylation of N -acetyltransferase 2 ( NAT2 ), a metabolic enzyme responsible for drug metabolism and detoxification, was correlated with clinical parameters indicating anti-tuberculosis drug-induced liver injury (ATDILI) in tuberculosis patients and might emerge as an ATDILI biomarker. NAT2 promoter methylation in blood leukocyte of 102 tuberculosis patients (49 ATDILI cases and 53 non-ATDILI cases) and 100 healthy controls were quantified using quantitative real-time methylation-specific polymerase chain reaction. Compared to healthy volunteers, tuberculosis patients had significantly reduced NAT2 demethylation index. Compared with non-ATDILI patients, NAT2 demethylation index was significantly decreased in ATDILI patients. An independent association was found between lower NAT2 demethylation index and increased susceptibility to ATDILI. NAT2 demethylation index quantified after starting treatment within 1–7 days was negatively correlated with serum aminotransferases measured within 8–60 days of treatment. ROC curve analysis uncovered that NAT2 demethylation index was found to be a more sensitive and specific biomarker for ATDILI when compared to serum aminotransferases measured following treatment initiation within 1–7 days. Kaplan–Meier analysis unveiled a notable association between lower NAT2 demethylation index and a higher incidence of ATDILI in tuberculosis patients, as confirmed by Cox regression analysis while accounting for confounding variables. A reduction in NAT2 demethylation index could reflect ATDILI progression and potentially be used as a new, specific biomarker for ATDILI.