Simplified Chronic Hepatitis B Antiviral Initiation Criteria in Thailand: An Economic Evaluation.

OBJECTIVES: Criteria for antiviral treatment initiation in Thailand were complex and difficult to implement. This study determined the cost-effectiveness of 2 simplified antiviral treatment initiation criteria among patients with chronic hepatitis B in Thailand. METHODS: A hybrid model of the decision tree and Markov model was developed. Two simplified antiviral treatment initiation criteria were the expanded criteria, treating patients with hepatitis B surface antigen positive and viral load (hepatitis B virus deoxyribonucleic acid) >2000 IU/mL or cirrhosis by tenofovir alafenamide (TAF), and the test-and-treat criteria, treating patients with hepatitis B surface antigen positive and viral load >10 IU/mL or cirrhosis by TAF. PubMed was searched from its inception to July 2023 to identify input parameters. Best supportive care was chosen for patients who were ineligible for TAF. Incremental cost-effectiveness ratio per quality-adjusted life-year (QALY) was calculated. RESULTS: The expanded criteria and the test-and-treat could reduce the occurrence of patients progressing to hepatocellular carcinoma. In particular, both criteria could reduce 4846 new cases of hepatocellular carcinoma per 100 000 patients. The incremental cost-effectiveness ratios for the expanded criteria and the test-and-treat criteria were 24 838 Thai baht (THB)/QALY and 163 060 THB/QALY, respectively. CONCLUSIONS: At the current willingness to pay of 160 000 THB/QALY, the expanded criteria were cost-effective, but the test-and-treat criteria were not cost-effective to be the simplified antiviral treatment initiation criteria for patients with chronic hepatitis B in Thailand.

Clinical effects of Hibiscus sabdariffa Linn. on obesity treatment: A systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Obesity is associated with many chronic non-communicable diseases, including hypertension, diabetes, cardiovascular and cerebrovascular diseases, cancer, gallbladder disease, bone and joint disorders, skin diseases, fatty liver disease, etc. [1] The recent report revealed that overweight and obesity were prevalent in 60% of the adult population. Several studies have been published to determine the effect of Hibiscus sabdariffa Linn. on obesity treatment, but the findings are still inconclusive. The purpose of this study was to determine the efficacy and safety of H. sabdariffa Linn in the treatment of obesity. METHODS: We searched PubMed, EMBASE, and CENTRAL from inception to February 2024. Randomized controlled trials (RCTs) were included if they explored the effect of H. sabdariffa on one of the following outcomes: body weight, body mass index (BMI), waist circumference, and waist-to-hip ratio. A random-effects model was used to meta-analyze the data. I2 was used to quantify statistical heterogeneity among the included RCTs. PROSPERO registered protocol: CRD42023408880. RESULTS: A total of six RCTs with 339 participants were included. Four trials used H. sabdariffa extract in capsules as the intervention of interest compared to placebo, while the other two trials used H. sabdariffa tea compared to black or green tea. Our meta-analyses showed that the mean difference in weight reduction between H. sabdariffa and control was -0.27 kilograms (95% confidence interval (CI); -1.98 to 1.42, I2 = 0.0%). The mean differences for BMI and waist circumference reduction were -0.06 kilograms/meter2 (95% CI; -0.58 to 0.47, I2 = 0.0%) and -0.20 centimeters (95% CI; -2.06 to 1.66, I2 = 0.00%). No safety concerns were reported in the included studies. CONCLUSION: Our study did not show a clinical benefit of H. sabdariffa extract in obesity treatment. However, further high-quality RCTs with a longer treatment duration and a standard dose are still warranted.

Polymer Matrix and Manufacturing Methods in Solid Dispersion System for Enhancing Andrographolide Solubility and Absorption: A Systematic Review.

Background: Andrographolide (ADG) has poor aqueous solubility and low bioavailability. This study systematically reviews the use of solid dispersion (SD) techniques to enhance the solubility and absorption of ADG, with a focus on the methods and polymers utilized. Methodology: We searched electronic databases including PubMed, Web of Science, Scopus®, Embase and ScienceDirect Elsevier® up to November 2023 for studies on the solubility or absorption of ADG in SD formulations. Two reviewers independently reviewed the retrieved articles and extracted data using a standardized form and synthesized the data qualitatively. Results: SD significantly improved ADG solubility with up to a 4.7-fold increase and resulted in a decrease in 50% release time (T1/2) to less than 5 min. SD could also improve ADG absorption, as evidenced by higher Cmax and AUC and reduced Tmax. Notably, Soluplus-based SDs showed marked solubility and absorption enhancements. Among the five SD techniques (rotary evaporation, spray drying, hot-melt extrusion, freeze drying and vacuum drying) examined, spray drying emerged as the most effective, enabling a one-step process without the need for post-milling. Conclusions: SD techniques, particularly using Soluplus and spray drying, effectively enhance the solubility and absorption of ADG. This insight is vital for the future development of ADG-SD matrices.

Economic Evaluation of the Thai Diagnostic Autism Scale for Autism Spectrum Disorder Diagnosis in Children Aged 1-5 Years Old.

The Thai Diagnostic Autism Scale (TDAS) was developed for autism spectrum disorder (ASD) diagnosis in Thai children aged 1-5 years. Previous studies have indicated its good performance; however, additional health resources and healthcare providers are necessary for evaluation. Therefore, this study aimed to assess the cost-effectiveness of TDAS compared to clinical diagnosis (ClinDx) for ASD diagnosis in Thai children aged 1-5 years from a societal perspective. The analysis employed a hybrid model consisting of a decision tree model for a diagnostic phase with a state transition model for a follow-up phase. A literature review was conducted to determine TDAS performance and the relative risk of death in patients with ASD. Direct medical costs were assessed through a retrospective medical records review, and a cross-sectional survey was conducted to determine direct nonmedical costs, ASD severities, and utility values. The cost of TDAS was derived from a healthcare provider interview (n = 10). The incremental cost-effectiveness ratio (ICER) compared the total lifetime cost and quality-adjusted life years (QALY) between TDAS and ClinDx. We found that TDAS could improve QALY by 1.96 but increased total lifetime cost by 5577 USD, resulting in an ICER of 2852 USD/QALY. Sensitivity analysis indicated an 81.16% chance that TDAS is cost-effective. The probabilities of different ASD severities were key influencing factors of the findings. In conclusion, TDAS is the cost-effective option for ASD diagnosis in Thai children aged 1-5 years compared to ClinDx, despite some uncertainties around inputs. Further monitoring and evaluation are warranted if TDAS is to be implemented nationwide.

Impact of type of anticoagulant on clinical outcomes in cancer patients who had atrial fibrillation.

To date, evidence on optimal anticoagulant options in patients with AF who concurrently have active cancer remains elusive. To describe anticoagulant patterns and clinical outcomes among patients with a concomitant diagnosis of AF and cancer. Data were obtained from the University of Utah and Huntsman Cancer Institute (HCI) Hospitals. Patients were included if they had diagnosis of AF and cancer. Outcome was type and pattern of anticoagulant. Clinical outcomes were stroke, bleeding and all-cause mortality. From October 1999 to December 2020, there were 566 AF patients who concurrently had active cancer. Mean age ± standard deviation was 76.2 ± 10.7 and 57.6% were males. Comparing to warfarin, patients who received direct oral anticoagulant (DOACs) were associated with similar risk of stroke (adjusted hazard ratio, aHR 0.8, 95% confidence interval [CI] 0.2-2.7, P = 0.67). On contrary, those who received low-molecular-weight heparin (LMWH) were associated with significantly higher risk of stroke comparing to warfarin (aHR 2.4, 95% CI 1.0-5.6, P = 0.04). Comparing to warfarin, DOACs and LMWH was associated with similar risk of overall bleeding with aHR 1.1 (95% CI 0.7-1.6, P = 0.73) and aHR 1.1 (95% CI 0.6-1.7, P = 0.83), respectively. Patients who received LMWH but not DOACs were associated with increased risk of death as compared to warfarin, aHR 4.5 (95% CI 2.8-7.2, P < 0.001) and 1.2 (95% CI 0.7-2.2, P = 0.47). In patients with active cancer and AF, LMWH, compared to warfarin, was associated with an increased risk of stroke and all-cause mortality. Furthermore, DOACs was associated with similar risk of stroke, bleeding and death as compared to warfarin.

Risk prediction algorithms in guiding antiviral therapy initiation among patients with chronic hepatitis B in Thailand: an economic evaluation and budget impact analysis.

OBJECTIVE: Several risk prediction algorithms have been developed to guide antiviral therapy initiation among patients with chronic hepatitis B (CHB). This study assessed the cost-effectiveness and budget impact of three risk prediction algorithms among patients with CHB in Thailand. METHODS: A decision tree with a Markov model was constructed. Three risk prediction algorithms were compared with current practices including HePAA, TREAT-B and REACH-B. PubMed was searched from its inception to December 2022 to identify inputs. Tenofovir alafenamide and best supportive care were selected for antiviral-eligible patients, and incremental cost-effectiveness ratios per quality-adjusted life year (QALY) were calculated. RESULTS: Our base case analysis showed that HePAA and REACH-B could provide better QALY (0.098 for HePAA and 0.921 for REACH-B) with decreased total healthcare costs (-10909 THB for HePAA and -8,637 THB for REACH-B). TREAT-B provided worse QALY (-0.144) with increased total healthcare costs (10,435 THB). The budget impacts for HePAA and REACH-B were 387 million THB and 3,653 million THB, respectively. CONCLUSION: HePAA and REACH-B algorithms are cost-effective in guiding antiviral therapy initiation. REACH-B is the most cost-effective option, but has a high budget impact. Policymakers should consider both cost-effectiveness and budget impact findings when deciding which algorithm should be implemented.

The Association of Pre-operative Serum Albumin Levels and Post-operative In-Hospital Death in Patients Undergoing Gastrointestinal Surgeries in Thailand: A Retrospective Cohort Study.

BACKGROUND: Pre-operative hypoalbuminemia is known to predict negative outcomes for patients undergoing major surgeries. However, various cut-off points for starting exogenous albumin have been recommended. OBJECTIVE: This study investigated the association between pre-operative severe hypoalbuminemia, in-hospital death, and length of hospital stay in patients undergoing gastrointestinal surgery. METHODS: A retrospective cohort study using a database analysis was undertaken on hospitalized patients who underwent major gastrointestinal surgery. The pre-operative serum albumin level was classified into three groups: severe hypoalbuminemia (< 2.0 mg/dL) and non-severe hypoalbuminemia (≥ 2.0-3.4 g/dL) and normal level (3.5-5.5 g/dL). To compare between different cut-offs, a sensitivity analysis using another albumin level classification as severe hypoalbuminemia (< 2.5 mg/dL) and non-severe hypoalbuminemia (≥ 2.5-3.4 g/dL) and normal level (3.5-5.5 g/dL) was applied. The primary outcome was post-operative in-hospital death. Propensity-score adjusted regression analyses were applied. RESULTS: A total of 670 patients were included. Their average age was 57.4 ± 16.3 years, and 56.1% were men. Only 59 patients (8.8%) had severe hypoalbuminemia. Overall, a total of 93 in-hospital deaths (13.9%) occurred among all included patients, but there were 24/59 (40.7%) deaths among patients with severe hypoalbuminemia, 59/302 (19.5%) deaths among patients with non-severe hypoalbuminemia, and 10/309 (3.2%) deaths among patients with normal albumin level. The adjusted odds ratio for post-operative in-hospital death comparing patients with severe hypoalbuminemia and patients with normal albumin level was 8.11 (3.31-19.87; p < 0.001), while the odds ratio for in-hospital death comparing patients with non-severe and patients with normal albumin level was 3.89 (1.87-8.10; p < 0.001). A sensitivity analysis showed similar findings, the odds ratio for in-hospital death for severe hypoalbuminemia (cut-off as < 2.5 g/dL) was 7.44 (3.38-16.36; p < 0.001), while the odds ratio for in-hospital death for severe hypoalbuminemia (cut-off as 2.5-3.4 g/dL) was 3.02 (1.40-6.52; p = 0.005). CONCLUSIONS: Severe pre-operative hypoalbuminemia in patients undergoing gastrointestinal surgery was associated with an increased risk of in-hospital mortality. The risk of death for patients with severe hypoalbuminemia was relatively similar when using different cut-offs such as < 2.0 and <2.5 g/dL.

Economic Evaluation of Direct Oral Anticoagulants Compared to Warfarin for Venous Thromboembolism in Thailand: A Cost-Utility Analysis.

BACKGROUND: Direct oral anticoagulants (DOACs) have been used for venous thromboembolism (VTE) in Thailand. However, they have not been listed in the National List of Essential Medicines (NLEM). A cost-effectiveness analysis is needed to aid policymakers in deciding whether DOACs should be listed in the NLEM. This study aimed to assess the cost-effectiveness of DOACs for patients with VTE in Thailand. METHODS: A cohort-based state transition model was constructed from a societal perspective with a lifetime horizon. All available DOACs, including apixaban, rivaroxaban, edoxaban, and dabigatran, were compared with warfarin. A 6-month cycle length was used to capture all costs and health outcomes. The model consisted of nine health states, including VTE on treatment, VTE off treatment, recurrent VTE, clinically relevant non-major bleeding, gastrointestinal bleeding, intracranial bleeding, post-intracranial bleeding, chronic thromboembolic pulmonary hypertension, and death. All inputs were based on a comprehensive literature review. The model outcomes included total cost and quality-adjusted life-years (QALYs) with a 3% annual discount rate. A fully incremental cost-effectiveness analysis and the incremental cost-effectiveness ratio (ICER) per QALY gained were calculated at a willingness-to-pay (WTP) of THB 160,000/QALY ($5003). The robustness of the findings was assessed using deterministic and probabilistic sensitivity analyses. RESULTS: All DOACs were associated with a decreased risk of VTE recurrence and intracranial hemorrhage. In the base-case analysis, apixaban could increase 0.16 QALYs compared with warfarin. An ICER for apixaban was 269,809 Thai baht (THB)/QALY ($8437/QALY). Rivaroxaban had a better QALY than warfarin at 0.09 QALYs with an ICER of 757,363 THB/QALY ($23,682/QALY). Edoxaban and dabigatran could also increase by 0.10 QALYs with an ICER of 709,945 THB ($22,200) and 707,145 THB ($22,122)/QALY, respectively. Our probabilistic sensitivity analyses indicated that warfarin had a 99.8% possibility of being cost-effective, while apixaban had a 0.2% possibility of being cost-effective at the current WTP. Other DOACs had no possibility of being cost-effective. CONCLUSIONS: All DOACs were not cost-effective for VTE treatment at the current WTP in Thailand. Apixaban is likely to be the best option among DOACs.

Telepharmacy services to support patients with epilepsy in Thailand: A descriptive study.

Background: Telepharmacy shows an effective option to provide pharmacy services in several settings. It could improve patients' outcomes and save costs. However, the impact of a telepharmacy services in low resource settings remains limited. Objectives: This study assessed the feasibility and effect of telepharmacy services on patient-reported clinical and economic outcomes among patients with epilepsy in Thailand. Methods: A prospective descriptive study was conducted at a university hospital. Patients with epilepsy visiting the clinic from February 2021-December 2021 were included. Telepharmacy services were provided by hospital pharmacists through an application platform. Patients met a pharmacist synchronously using a video conference feature embedded in our developed website. Patients were interviewed for improved clinical symptoms, drug-related problems (DRPs), and health and social behaviors. Travel costs, food and accommodation costs and productivity costs due to hospital visits were also evaluated. Results: A total of 80 patients were included. Of those, 39 patients (48.75%) were men, averaging 35.44 ± 15.09 years old. A total of 22 patients (27.50%) reported better clinical symptoms after the telepharmacy service. Sixty-four DRPs (69.56%) were observed, along with 28 health and social behavior problems (30.44%). The most common DRPs were adverse drug reactions (20/64; 69.56%), followed by patients' non-adherence (20/64; 31.25%). Sixty-six problems (68.04%) were corrected during the telepharmacy service. From the patient's perspective, the average direct nonmedical cost per visit was 1257 ± 857 THB/visit. Travel costs were the major cost driver, accounting for 67.7% of the total cost. Cost savings averaged 6511 ± 4996 THB/year or 54.75% of usual care. Conclusion: Telepharmacy services are likely to improve patient outcomes, detect DRPs, and effectively provide cost-savings. However, further studies hosting a larger number of participants are warranted to assess the impacts of telepharmacy services.

Cost-Utility Analysis of Biologic Disease-Modifying Antirheumatic Drugs for Patients With Psoriatic Arthritis in Thailand.

OBJECTIVES: This study aimed to assess the cost-effectiveness of biologic disease-modifying antirheumatic drugs (bDMARDs) for treating patients with psoriatic arthritis who failed conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). METHODS: A decision tree and Markov model were constructed to capture long-term costs and outcomes from a societal perspective. Patients with psoriatic arthritis who failed 2 previous csDMARDs were modeled over a 3-month cycle with a lifetime horizon. Clinical probabilities were derived from a published meta-analysis. Prices of bDMARDs were proposed by pharmaceutical companies. Other costs and utilities were based on data in Thailand. All costs and outcomes were discounted at a 3% annual rate. Incremental cost-effectiveness ratio and a series of sensitivity analyses were performed. RESULTS: All 11 bDMARDs (3 infliximab originator and biosimilars, 2 etanercept originator and biosimilar, golimumab, 2 secukinumab 150 mg and 300 mg, 3 adalimumab biosimilars) gained better quality-adjusted life-years (QALYs) with more costly than csDMARDs. Infliximab had the highest QALYs compared with other bDMARDs. Only secukinumab 150 mg showed the incremental cost-effectiveness ratio below the Thai threshold of 5152 US dollars per QALY. Cost of bDMARDs was the most influential factor. CONCLUSIONS: At the current price, secukinumab 150 mg shows the value for money in the Thai context. Price negotiation is of great importance for other bDMARDs.

Effects of Anticholinergics on Death Rattle: A Systematic Review and Network Meta-Analysis.

Background: Anticholinergics have been used to treat death rattle (DR) in dying patients with palliative care. However, the effect of anticholinergics is still controversial. No quantitative summary of their effects is reported. Objective: This study aimed to systematically review and quantitatively synthesize the effect of anticholinergics on DR treatment and prophylaxis. Design: A systematic search was performed in the electronic databases (PubMed, Embase®, and Cumulative Index to Nursing and Allied Health Literature [CINAHL]) from inception to October 2021. Studies conducted to determine the effect of anticholinergics compared with other anticholinergics or placebo on noise reduction score in dying patients were included. A network meta-analysis was performed for DR treatment. The effect of anticholinergics at four hours was assessed. A pairwise meta-analysis was performed for DR prophylaxis. Results: A total of nine studies were included with 1103 patients. Six studies were randomized controlled trials, and three studies were cohort studies. Seven studies were conducted for DR treatment, while two studies were conducted for DR prophylaxis. For DR treatment, no statistically significant difference was observed between each anticholinergic (hyoscine hydrobromide, hyoscine butyl bromide, atropine, and glycopyrrolate) and placebo and among any anticholinergics. However, the surface under cumulative ranking curve indicated that hyoscine butyl bromide had the highest surface under the cumulative ranking curve (SUCRA) with 71.3%. For DR prophylaxis, the relative risk of DR occurrence for hyoscine butyl bromide was 0.23 (0.04, 1.18; I2 = 84.5%) compared with no treatment. Conclusion: This study showed no strong evidence of the regular use of anticholinergics for DR treatment. In addition, hyoscine butyl bromide appears to have a high potential for DR prophylaxis.

Efficacy and Safety of Cytisine in Combination with a Community Pharmacists' Counselling for Smoking Cessation in Thailand: A Randomized Double-Blinded Placebo-Controlled Trial.

BACKGROUND: Cytisine is a prospective pharmacological alternative for community pharmacy smoking cessation services. However, it has not yet been licensed because of a lack of efficacy and safety information in Thailand. OBJECTIVE: The aim of this study was to evaluate the efficacy of cytisine in combination with community pharmacists' counselling on smoking cessation in a community pharmacy in ThailandDesign. Setting, participants, and interventions: A double-blinded randomized placebo-controlled trials was carried out. Participants aged >18 years old who smoked >10 tobaccos/day were randomly assigned to receive cytisine or placebo and five sessions of counselling by a community pharmacist. The primary outcome was a continuous abstinence rate (CAR) at week 48. The CAR was also measured at weeks 2, 4, 12, and 24. Adverse events were monitored. RESULTS: A total of 132 participants were included, with 67 receiving cytisine and 65 receiving a placebo. Approximately 95% of participants were male. The CARs were determined to be 14.93% and 6.15% for cytisine and placebo, respectively, at week 48. The relative risk (RR) was 2.41 (95% confidence interval (CI); 0.80-7.35, p = 0.102). The RRs for CAR at weeks 2, 4, 12, and 24 were 2.43, 2.91, 2.50, and 1.78, respectively. Only the RRs for weeks 2, 4, and 12 were statistically significant. Common and non-serious gastrointestinal and neurological adverse events were observed. CONCLUSION: Cytisine, when combined with community pharmacists' counselling, did not statistically improve the CAR at week 48, although it did improve the CAR at weeks 2, 4, and 12. Adverse events of cytisine were common and non-serious (registration number: TCTR20180312001).

The impact of Thai multidisciplinary smoking cessation program on clinical outcomes: A multicentre prospective observational study.

Introduction: Tobacco use is the leading preventable cause of morbidity and mortality worldwide. Since 2010, Thailand has implemented a multidisciplinary smoking cessation clinic, which provides smoking cessation services, but the effectiveness of the clinics was not formally evaluated. This study was conducted to assess the real-world effectiveness of this multidisciplinary smoking cessation program. Methods: We conducted a prospective, multicentre, observational study on Thai participants aged 13 years and older in 24 smoking cessation clinics across Thailand's 13 health regions. Each clinic offered smoking cessation interventions according to the well-established 5As model for smoking cessation (Ask, Advise, Assess, Assist, and Arrange). Outcomes of interest were continuous abstinence rates (CAR) at 3 and 6 months. Biochemical confirmation and self-reporting were used to assess the outcomes. Descriptive statistics (mean, SD, median, IQR, and percentage) were used to analyze the smoking cessation outcomes in both intention-to-treat and per-protocol analysis approaches. Results: Smokers receiving services from the Thai multidisciplinary smoking cessation clinics had CAR of 17.49 and 8.33% at 3 and 6 months, respectively. For those with cardiovascular disease (CVD) or cerebrovascular disease, CAR was found to be 26.36% at 3 months and 13.81% at 6 months. While participants with chronic obstructive pulmonary disease (COPD) had CAR ranging from 32.69% at 3 months to 17.31% at 6 months. Conclusion: The multidisciplinary team smoking cessation clinic was effective in assisting smokers in quitting smoking. The effectiveness of the clinic was more pronounced for smokers with CVD, cerebrovascular disease, or COPD. Findings from this study support a decision to include multidisciplinary smoking cessation clinics in the universal health care benefits package.

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.

Trends in advanced oral drug delivery system for curcumin: A systematic review.

Although curcumin is globally recognized for its health benefits, its clinical application has been restricted by its poor aqueous solubility and stability. To overcome these limitations, nanocarrier-based drug delivery systems (NDS) are one of the most effective approaches being extensively explored over the last few decades to improve curcumin's physicochemical and pharmacological effects. Various NDS could provide productive platforms for addressing the formulation challenge of curcumin, but evidence of such systems has not been summarized. This study aimed to systematically review current evidence of lipid and polymer-based NDS for an oral delivery of curcumin focusing on in vivo models and clinical studies. Among the 48 included studies, 3 studies were randomized controlled clinical trials, while 45 studies were animal models. To date, only five curcumin NDS have been studied in healthy volunteers: γ-cyclodextrin, phytosome, liposome, microemulsion and solid dispersion, while most curcumin NDS have been studied in animal models. Most included studies found that NDS could increase oral bioavailability of curcumin as compared to free curcumin. In conclusion, this systematic review showed evidence of the positive effect of NDS for enhancement of oral bioavailability of curcumin. EXECUTIVE SUMMARY: Curcumin is globally recognized for its health benefits, but its clinical application has been limited by its poor aqueous solubility and stability, which causes poor absorption in the gastrointestinal tract (GI tract) via oral administration. Nanocarrier-based drug delivery systems (NDS) are considered as a productive platform to solve the formulation challenge of curcumin, but evidence of such systems has not been summarized. This study aimed to systematically review current evidence of lipid and polymer-based NDS for an oral delivery of curcumin focusing on in vivo models and clinical studies. Overall, most studies found that all studied NDS could increase the absorption of curcumin as compared to free curcumin. Curcumin was rapidly absorbed and exhibited a long residence time after oral administration of curcumin NDS. In summary, this systematic review showed positive impacts of NDS for enhancement of oral absorption of curcumin.

Economic Burdens for Treatment of Patients With Type 2 Diabetes in North Thailand: A Hospital-Based Observational Study.

Purpose: Diabetes and its complications pose an economic burden to healthcare systems, family, and society. Therefore, this study aimed to estimate the real-world financial burden of type 2 diabetes (T2D) treatment, complications, and cardiovascular death. Materials and Methods: An electronic database of the largest university-affiliated hospital in the North of Thailand was retrieved for a 10-year period (2009-2019). We used the International Classification of Disease 10th Revision codes of diabetes and complications to obtain relevant patient records. All included records based on the inclusion and exclusion criteria were analyzed. Expenditures for diabetes treatment, complications, and cardiovascular death for two years were reported as mean, standard deviation, median, and interquartile range. Results: Of a total of 9,161 patient records, the average age of patients was 57.8 ± 12.7 years. The average total outpatient cost was THB 22,874 ± 38,066 (US$ 759 ± 1,264) for the first year and THB 23,462 ± 34,441 (US$ 779 ± 1,143) for the second year. The average inpatient expenditure was THB 160,790 ± 411,607 (US$ 5,338 ± 13,666) for the first year and THB 181,804 ± 190,257 (US$ 6,036 ± 6,317) for the second year. Drug was the main component for outpatient expenditure while surgery was the main component for inpatient expenditure. Diabetes patients with complications incurred a greater cost of treatment than those without complications. Cardiovascular death led to about seven times higher cost of treatment than the average total cost of diabetes treatment. Heart failure complications (THB 846,345 ± 752,884 or US$ 28,099 ± 24,996) had the highest inpatient costs compared with other complications in the first year. Stroke complications (THB 71,927 ± 143,414 or US$ 2,388 ± 4,761) had the highest outpatient costs compared with other complications. In general, the first-year expenditure was higher than the second year for all complications. Conclusions: Diabetes incurs a substantial financial burden resulting from its complications. Effective management of diabetes with a multi-sectoral effort from government, providers, patients, and private is required.

Public Health Value of a Hypothetical Pneumococcal Conjugate Vaccine (PCV) Introduction: A Case Study.

Background: Understanding the public health value of a vaccine at an early stage of development helps in valuing and prioritizing the investment needed. Here we present the potential cost-effectiveness of an upcoming 12 valent pneumococcal conjugate vaccine (PCV 12) in the case study country, Thailand. Methods: The cost-effectiveness analysis included a hypothetical scenario of three doses (2 + 1 regimen) PCV12 introduction in the national immunization program of Thailand compared to no PCV, PCV10, and PCV13 among <6 months old from a societal perspective with a lifetime horizon and one-year cycle length. Data from Thailand, as well as assumptions supported by the literature, were used in the analysis. The price of PCV12 was assumed similar to that of PCV10 or PCV13 for GAVI's eligible countries based on inputs from stakeholder meeting. A one-way sensitivity analysis was conducted using 0.5−1.5 times the base price of PCV12. Results were presented in incremental cost-effectiveness ratio (ICER) in terms of monetary value per quality-adjusted life-year (QALY) gained. Results: Vaccination with PCV12 among a hypothetical cohort of 100,000 Thai children is expected to avert a total of 5358 cases which includes 5 pneumococcal meningitis, 43 pneumococcal bacteremia, 5144 all-cause pneumonia, and 166 all-cause acute otitis media compared to no vaccination. The national PCV12 vaccination program is a cost-saving strategy compared to the other three strategies. The one-way sensitivity analysis showed PCV12 is a cost-saving strategy when 1.5 times the base price of PCV12 was assumed. Conclusions: Within the limitations of hypothetical assumptions and price points incorporated, the study indicates the potential public health value of PCV12 in Thailand.

Effectiveness of interventions for middle-aged and ageing population with neck pain: a systematic review and network meta-analysis protocol.

INTRODUCTION: Neck pain (NP) is a common musculoskeletal complaint and is increasing in prevalence. Current clinical practice guidelines and systematic reviews recommended conservative, pharmacological and invasive interventions for individuals with NP. However, optimal management specifically for those who are middle-aged or older adults (≥45 years) is not available; and important considering our ageing population. METHODS AND ANALYSIS: A systematic review with network meta-analysis (NMA) will be conducted following the Cochrane guidelines. Eligibility criteria include randomised controlled/clinical trials evaluating any of acute (<3 months) or chronic (≥3 months) non-specific NP, whiplash associated disorders, cervical radiculopathy and cervicogenic headache. Any interventions and outcome measures detailed within The International Classification of Functioning, Disability and Health domains will be included. Two independent reviewers will search key databases (AMED, CENTRAL, CINAHL, Embase, MEDLINE, PEDro and PsycINFO), grey literature, key journals and reference lists in May 2022. Two reviewers will decide eligibility and assess risk of bias (ROB) of included studies. The kappa statistic will be used to evaluate agreement between the reviewers at each stage. Data will be extracted by one reviewer and checked for accuracy by a second reviewer. Descriptive data and ROB will be summarised and tabulated. Traditional pairwise meta-analysis using random-effect model will be performed for all direct comparisons, and NMA using a frequentist random-effect model then performed based on NP classification where possible. A network of traditional pairwise meta-analysis allows comparisons of multiple interventions from both direct and indirect evidence to provide a hierarchal establishment for enhancing decision making of clinical practitioners. ETHICS AND DISSEMINATION: Ethic approval is not required as the study is a literature review. The findings will be shared with the national and international researchers, healthcare professionals and the general public through publishing in a peer-reviewed journal and presentations at conferences. PROSPERO REGISTRATION NUMBER: CRD42021284618.