A systematic review of the efficacy and safety of turmeric in the treatment of digestive disorders.

Turmeric has been gaining popularity as a treatment option for digestive disorders, although a rigorous synthesis of efficacy has not been conducted. This study aimed to summarize the evidence for the efficacy and safety of turmeric in the treatment of digestive disorders, including inflammatory bowel diseases (IBD), irritable bowel syndrome (IBS), dyspepsia, gastroesophageal reflux disease, and peptic ulcers. Literature searches were conducted in Medline, EMBASE, AMED, the Cochrane Central Register of Control Trials, and Dissertation Abstracts from inception to November 15, 2021. Dual independent screening of citations and full texts was conducted and studies meeting inclusion criteria were retained: randomized controlled trials (RCT) and comparative observational studies evaluating turmeric use in people of any age with one of the digestive disorders of interest. Extraction of relevant data and risk of bias assessments were performed by two reviewers independently. Meta-analysis was not conducted due to high heterogeneity. From 1136 citations screened, 26 eligible studies were retained. Most studies were assessed to have a high risk of bias, and many had methodological limitations. Descriptive summaries suggest that turmeric is safe, with possible efficacy in patients with IBD or IBS, but its effects were inconsistent for other conditions. The efficacy of turmeric in digestive disorders remains unclear due to the high risk of bias and methodological limitations of the included studies. Future studies should be designed to include larger sample sizes, use rigorous statistical methods, employ core outcome sets, and adhere to reporting guidance for RCTs of herbal interventions to facilitate more meaningful comparisons and robust conclusions.

Real-World Costs and Cost-Effectiveness Analysis of Rabbit-Antithymocyte Globulin Versus Oxymetholone in Acquired Aplastic Anemia in Thailand.

OBJECTIVES: This study aimed to compare rabbit-antithymocyte globulin and cyclosporine (rATG/CsA) with oxymetholone in terms of direct medical expenditures and economic evaluation in severe acquired aplastic anemia (SAA) and very severe acquired aplastic anemia (vSAA) patients. METHODS: Patients with SAA/vSAA who initiated treatment with rATG/CsA or oxymetholone between 2004 and 2018 were included. Trial-based cost-effectiveness evaluation in healthcare provider perspective was performed. Direct medical costs were retrieved from hospital database, inflated, and converted to 2020 US dollar (30.01 Baht per US dollar). One-way sensitivity analysis and probabilistic sensitivity analysis by nonparametric bootstrap was performed. RESULTS: After 2-year follow-up, the total mean (SD) direct medical expenditures per patient for oxymetholone and rATG/CsA group were $8 514.48 ($12 595.67) and $41 070.88 ($22 084.04), respectively. Nevertheless, oxymetholone had significant lower survival rate than rATG/CsA (P=.001) but higher in second-year blood transfusion need (71.4% vs 18.2%) and hospitalization (14.3% vs 0%). The incremental cost-effectiveness ratio was $45 854.08 per life-year gained when rATG/CsA was used instead of oxymetholone (95% CI $24 244.03-$143 496.67 per life-year gained). The probabilistic sensitivity analysis indicated that rATG/CsA had no chance of being cost-effective for SAA/vSAA when willingness to pay threshold of one to 3 times of national gross domestic product per capita was applied. CONCLUSIONS: Oxymetholone remains a viable alternative in resource-limited country. Despite its high cost, the rATG/CsA is a preferred treatment option because of the significant advantages on reducing mortality, treatment complications, and hospitalization.

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.

Quality of life, out-of-pocket expenditures, and indirect costs among patients with the central nervous system tumors in Thailand.

Objectives: The aim of this study was to investigate out-of-pocket (OOP) expenditures, indirect costs, and health-related quality of life (HRQoL) associated with the central nervous system (CNS) tumors in Thailand. Materials and Methods: A prospective study of CNS tumor patients who underwent first tumor resection at a tertiary care institution in Thailand was conducted. Patients were interviewed during hospitalization for undergoing first surgery. Within 6 months, they were interviewed once more if the disease continued to progress. Costs collected from a patient perspective and converted to 2019 US dollars. For dealing with these skewed data, a generalized linear model was used to investigate the effects of disease severity (malignancy, progressive disease, Karnofsky performance status score, and histology) and other factors on costs (OOP, informal care, productivity loss, and total costs). P < 0.05 was considered statistical significant for all analysis. Results: Among a total of 123 intracranial CNS tumor patients, there were 83 and 40 patients classified into benign and malignant, respectively. In the first brain surgery, there was no statistical difference in HRQoL between patients with benign and malignant tumors (P = 0.072). However, patients with progressive disease had lower HRQoL mean scores at pre-operative and progressive disease periods were 0.711 (95% confidence interval [CI]: 0.662-0.760) and 0.261 (95% CI: 0.144-0.378), respectively. Indirect expenditures were the primary cost driver, accounting for 73.81% of annual total costs. The total annual costs accounted for 59.81% of the reported patient's income in malignant tumor patients. The progressive disease was the only factor that was significantly increases in all sorts of costs, including the OOP (P = 0.001), the indirect costs (P = 0.013), and the total annual costs (P = 0.001). Conclusion: Although there was no statistical difference in HRQoL and costs between patients with benign and malignant tumor, the total costs accounted for more than half of the reported income in malignant tumor patients. The primary cause of significant increases in all costs categories was disease progression.

Prognostic Impact of the Combination of MGMT Methylation and TERT Promoter Mutation in Glioblastoma.

Background The concept of combinational analysis between the methylation of O 6 -methylguanine-DNA methyltransferase ( MGMT ) and telomerase reverse transcriptase promoter ( pTERT ) mutation in glioblastoma (GBM) has been reported. The main study objective was to determine the prognosis of patients with GBM based on MGMT/pTERT classification, while the secondary objective was to estimate the temozolomide effect on the survival time of GBM with MGMT/pTERT classification. Methods A total of 50 GBM specimens were collected after tumor resection and were selected for investigating MGMT methylation and pTERT mutation. Clinical imaging and pathological characteristics were retrospectively analyzed. Patients with MGMT/pTERT classification were analyzed using survival analysis to develop the nomogram for forecasting and individual prognosis. Results All patients underwent resection (total resection: 28%, partial resection: 64%, biopsy: 8%). Thirty-two percent of all cases received adjuvant temozolomide with radiotherapy. Sixty-four percent of the case was found methylated MGMT , and 56% of the present cohort found pTERT mutation. Following combinational analysis of biomarkers, results showed that the GBMs with methylated MGMT and wild-type pTERT had a superior prognosis compared with other subtypes. Using Cox regression analysis with multivariable analysis, the extent of resection, postoperative chemoradiotherapy, MGMT/pTERT classification were associated with a favorable prognosis. Hence, a web-based nomogram was developed for deploying individual prognostication. Conclusions The interaction of MGMT methylation and pTERT mutation was confirmed for predicting prognosis. The results from the present study could help physicians create treatment strategies for GBM patients in real-world situations.

Predicting the Health-related Quality of Life in Patients Following Traumatic Brain Injury.

Background Traumatic brain injury (TBI) commonly causes death and disability that can result in productivity loss and economic burden. The health-related quality of life (HRQoL) has been measured in patients suffering from TBI, both in clinical and socioeconomic perspectives. The study aimed to assess the HRQoL in patients following TBI using the European quality of life measure-5 domain-5 level (EQ-5D-5L) questionnaire and develop models for predicting the EQ-5D-5L index score in patients with TBI. Method A cross-sectional study was performed with 193 TBI patients who had completed the EQ-5D-5L questionnaire. The clinical characteristics, Glasgow coma scale (GCS) score, treatment, and Glasgow outcome scale (GOS) were collected. The total data was divided into training data (80%) and testing data (20%); hence, the factors affecting the EQ-5D-5L index scores were used to develop the predictive model with linear and nonlinear regression. The performances of the predictive models were estimated with the adjusted coefficient of determination (R 2 ) and the root mean square error (RMSE). Results A good recovery was found at 96.4%, while 2.1% displayed an unfavorable outcome. Moreover, the mean EQ-5D-5L index scores were 0.91558 (standard deviation [SD] 1.09639). GCS score, pupillary light reflex, surgery, and GOS score significantly correlated with the HRQoL scores. The multiple linear regression model had a high adjusted R 2 of 0.6971 and a low RMSE of 0.06701, while the polynomial regression developed a nonlinear model that had the highest adjusted R 2 of 0.6843 and the lowest RMSE of 0.06748. Conclusions A strong positive correlation between the physician-based outcome as GOS and HRQoL was observed. Furthermore, both the linear and nonlinear regression models were acceptable approaches to predict the HRQoL of patients after TBI. There would be limitations for estimating the HRQoL in unconscious or intubated patients. The HRQoL obtained from the predictive models would be an alternative method to resolve this problem.

The clinical characteristics and prognostic factors of multiple lesions in glioblastomas.

OBJECTIVE: Multiple glioblastomas (GBM) are the uncommon presentation of the disease. We aimed to identify the variables associated with the survival of patients with multiple GBMs according to the updated WHO classification. PATIENTS AND METHODS: We retrospectively reviewed 173 patients with newly diagnosed GBM between January 2003 and December 2018 and analyzed patients with multiple lesions at the time of diagnosis. The clinical, radiographic, and biomarkers were evaluated for descriptive analysis. The median overall survival and the Kaplan-Meier curves of the multiple GBMs were estimated. Furthermore, the Cox proportional hazard regression was the estimated hazard ratio for death according to various factors. Moreover, Schoenfeld's global test was performed for estimating assumptions. RESULTS: Of these, 30 (17.3%) of all GBMs were multiple GBMs, and multifocal and multicentric GBMs were found in 27 (90%) and 3 (10%), respectively. The median survival of the multiple GBMs was significantly shorter than solitary GBM (6 vs. 12 months, p = 0.003). Using Cox proportional hazards regression, the independent prognostic factors of multiple GBMs were concomitant Temozolomide with radiotherapy, wild-type IDH1, methylated MGMT promoter methylation in univariate analysis. In multivariable analysis, concomitant Temozolomide (TMZ) with radiotherapy (RT) was the strongest predictor associated with prognosis in multiple GBMs (0.40, 95%CI 0.16-0.97). CONCLUSIONS: Multiple lesions are uncommon findings in glioblastoma with poor prognostic features. Concomitant TMZ with RT was the strongest predictor of prognosis. In the future., IDH1 mutation and MGMT promoter methylation should be further explored as prognostic factors.

Revisiting Roles of Health Technology Assessment on Drug Policy in Universal Health Coverage in Thailand: Where Are We? And What Is Next?

OBJECTIVES: To describe the process, challenges, and future direction of health technology assessment (HTA), focusing on the drug selection of the National List of Essential Medicines (NLEM) in Thailand. METHODS: Literature and government documents were reviewed and analyzed by authors with experiences in HTA and drug policy in the country. RESULTS: The structure of HTA and its process in the drug selection of the NLEM were described, followed by the outcomes of the use of HTA. Examples of lowering drug prices, as a result of price negotiation using HTA, were presented. A few examples were also provided to demonstrate how decisions were made from considering factors beyond cost-effectiveness findings. Finally, challenges on various issues including improvement of HTA structure and process were discussed for the future direction of HTA in Thailand. CONCLUSIONS: HTA has been adopted as a tool for the drug selection of the NLEM to help Thailand achieve universal health coverage. Nevertheless, various challenges exist and need to be addressed.

Healthcare Resource Uses and Out-of-Pocket Expenses Associated with Pulmonary TB Treatment in Thailand.

BACKGROUND: In Thailand, pharmaceutical care has been recently introduced to a tertiary hospital as an approach to improve adherence to tuberculosis (TB) treatment in addition to home visit and modified directly observed therapy (DOT). However, the economic impact of pharmaceutical care is not known. OBJECTIVE: The aim of this study was to estimate healthcare resource uses and costs associated with pharmaceutical care compared with home visit and modified DOT in pulmonary TB patients in Thailand from a healthcare sector perspective inclusive of out-of-pocket expenditures. METHODS: We conducted a retrospective study using data abstracted from the hospital billing database associated with pulmonary TB patients who began treatment between 2010 and 2013 in three hospitals in Thailand. We used generalized linear models to compare the costs by accounting for baseline characteristics. All costs were converted to international dollars (Intl$) RESULTS: The mean direct healthcare costs to the public payer were $519.96 (95%confidence interval [CI] 437.31-625.58) associated with pharmaceutical care, $1020.39 (95% CI 911.13-1154.11) for home visit, and $887.79 (95% CI 824.28-955.91) for modified DOT. The mean costs to patients were $175.45 (95% CI 130.26-230.48) for those receiving pharmaceutical care, $53.77 (95% CI 33.25-79.44) for home visit, and $49.33 (95% CI 34.03-69.30) for modified DOT. After adjustment for baseline characteristics, pharmaceutical care was associated with lower total direct costs compared with home visit (-$354.95; 95% CI -285.67 to -424.23) and modified DOT (-$264.61; 95% CI -198.76 to -330.46). CONCLUSION: After adjustment for baseline characteristics, pharmaceutical care was associated with lower direct costs compared with home visit and modified DOT.

Out-of-Pocket Expenditures, Indirect Costs and Health-Related Quality of Life of Patients with Pulmonary Tuberculosis in Thailand.

BACKGROUND: Thailand's hospitals may adopt different supervision approaches to improve tuberculosis (TB) treatment adherence. OBJECTIVE: The aim of this study was to compare out-of-pocket (OOP) expenditures, indirect costs, and health-related quality of life (HRQoL) among TB patients who received pharmaceutical care (pharmacist-led patient education and telephone consultation), home visit, and self-administered therapy (SAT) in Thailand. METHODS: We conducted a prospective study to collect OOP expenditures, indirect costs, and HRQoL from a subsample of 104 adult pulmonary TB patients who started treatment between January and May 2014 in three hospitals. The three sources of data included patient interviews, patient medical records, and the hospital billing database. Patients were followed from January 2014 to March 2015. Relevant OOP expenditures collected during the interviews included (1) healthcare costs and other medications costs (e.g. vitamins, antibiotics, anti-cough) occurring in private healthcare units; and (2) costs of transportation, food, and accommodation. Productivity loss was measured using the self-reported amount of time a patient was unable to work due to TB, travel time to and from the hospital, time spent at the hospital (waiting time, consultation time, and hospitalizations), and time spent accompanying family members on outpatient visits or during hospitalizations. Cost differences among treatment strategies were adjusted for baseline characteristics by generalized linear models (GLMs). All costs were converted to international dollars (I$). RESULTS: A total of 256 eligible patients who started pulmonary TB treatment during the specified period were approached, with 104 patients being included in the analysis (29, 38, and 37 patients receiving pharmaceutical care, home visit, and SAT, respectively). Mean OOP expenditures per patient receiving pharmaceutical care, home visit, and SAT were I$907.56 [confidence interval (CI) I$603.80-I$1269.41], I$148.47 (CI I$109.49-I$194.89), and I$95.35 (CI I$69.11-I$129.63), respectively. The GLM indicated statistically significantly lower OOP expenditures for patients receiving either home visit or SAT (ratio of mean costs 0.247, CI 0.142-0.427; and 0.318, CI 0.187-0.540, respectively) than those receiving pharmaceutical care. Patient's indirect costs for receiving pharmaceutical care, home visit, and SAT were I$1925.68 (CI I$922.06-I$3284.94), I$2393.66 (CI I$1435.01-I$3501.98), and I$833.33 (CI I$453.87-I$1263.45), respectively. The GLM found no statistically significant differences in indirect costs for the home visit and SAT groups (ratio of mean costs 1.904, CI 0.754-4.802; and 0.792, CI 0.289-2.175, respectively) when pharmaceutical care was set as the reference. Mean utility scores [EuroQol five-dimensional three-level (EQ-5D-3L)] at baseline and treatment end were 0.679 and 0.830, 0.713 and 0.905, and 0.708 and 0.913 for patients receiving pharmaceutical care, home visit, and SAT, respectively. CONCLUSION: Pharmaceutical care patients experienced the highest OOP expenditures, compared with home visit and SAT patients. Home-visit patients reached the highest indirect costs and utility score improvements. A large-scale prospective study is required in order to strengthen evidence to support policy making regarding the most efficient use of limited resources for the management of TB.

Defining the scope of health technology assessment and types of health economic evaluation.

Health Technology Assessment (HTA) is a process that uses principles from across various disciplines, including medicine, sociology, economics, and ethics, to evaluate health technologies. Policy makers can use HTA as a tool to assess health technologies in a systematic, unbiased, transparent, and robust manner in order to make informed and evidence-based decisions. Generally, researchers begin an HTA by defining the overall scope of the assessment, after which they choose an appropriate type of health economic evaluation, one of the most important elements of HTA. The objective of this article is to provide recommendations about the scope of HTA as well as guidance on the kinds of health economic evaluation that are appropriate in the context of the new Thai HTA guidelines. A well-defined research question that addresses five major components-target population, technology or intervention, comparator outcome of interest, and perspective-is an essential

Cost-effectiveness of pharmaceutical management for osteoarthritis pain: a systematic review of the literature and recommendations for future economic evaluation.

BACKGROUND AND OBJECTIVE: Osteoarthritis (OA) is a highly prevalent and chronic condition characterized by pain and physical disability. Currently, many treatments are available, and they primarily target pain relief. The objectives of this study were to systematically review economic evaluations for pharmaceutical management of OA pain and to provide methodological recommendations for future economic evaluation. METHODS: Published literature was identified by searching the following bibliographic databases: MEDLINE (1948-16 November 2011) with In-Process records and EMBASE (1980-2011 Week 47) via Ovid; The Cochrane Library (Issue 4 of 4, 2011) and the Health Economic Evaluations Database (HEED) via Wiley; and PubMed (for non-MEDLINE records). The main search terms were OA and economic evaluations. Two reviewers independently screened all identified articles and extracted the data from those included in the final review. RESULTS: Twelve articles reporting the cost-effectiveness of various pharmaceuticals were included, with five being trial-based and seven being model-based economic evaluations. The mean health economics quality score of the included articles was 84 (minimum-maximum: 63-99). These evaluations varied in study design, treatments compared, and outcomes measured. CONCLUSION: The existing economic evaluations on pharmaceutical management of OA pain were of acceptable quality. Comparability of economic evaluations could be improved by selecting standard comparators, adopting a longer time horizon, and directly measuring health utilities.

Relative importance of attributes of drug benefit plans: Thai civil servants' perspective.

BACKGROUND: The drug benefit plan of Thailand's Civil Servant Medical Benefit Scheme (CSMBS) must be amended to control increasing costs; to that end, it is important to gather the views of beneficiaries before making changes to the benefit plan. OBJECTIVES: To examine the relative importance of attributes of drug benefit plans from the perspective of CSMBS beneficiaries. METHODS: Attributes and levels adopted from focus group discussions and a preliminary survey were used to develop a questionnaire concerning hypothetical drug benefit plans. A convenience sample of 650 CSMBS beneficiaries in Songkhla province was asked to rate the drug benefit plans. To determine the beneficiaries' decision models, judgment analysis was used. Policy-capturing analysis was used to examine the beneficiaries' preferences, and cluster analysis was conducted to explore the variability among judgment plans. Judgment policy insight was also examined. RESULTS: The results of the study showed that the beneficiaries weighed on cost-sharing as their most important attribute. The results remained unchanged, although only data from the beneficiaries who used the compensatory model were analyzed. The results of the cluster analysis showed that the largest cluster of beneficiaries weighed mostly on the cost-sharing attribute. The judgment policy insight results not only supported the finding that most beneficiaries focused on the cost-sharing attribute but also revealed that they might have the least understanding of how the formulary attribute affected beneficiaries' decision making. CONCLUSIONS: Cost-sharing was the most important attribute for the CSMBS beneficiaries. This study indicated that a possible preferred drug benefit plan should have no cost-sharing, permit access only to drugs listed in a closed formulary, allow beneficiaries to obtain 3 months of drugs, and allow them to obtain drugs from either a community pharmacy or a government hospital.