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Background Systematic reviews and meta-analyses of randomized clinical trials (RCTs) have reported the benefits of ketogenic diets (KD) in various participants such as patients with epilepsy and adults with overweight or obesity . Nevertheless, there has been little synthesis of the strength and quality of this evidence in aggregate. Methods To grade the evidence from published meta-analyses of RCTs that assessed the association of KD, ketogenic low-carbohydrate high-fat diet (K-LCHF), and very low-calorie KD (VLCKD) with health outcomes, PubMed, EMBASE, Epistemonikos, and Cochrane database of systematic reviews were searched up to February 15, 2023. Meta-analyses of RCTs of KD were included. Meta-analyses were re-performed using a random-effects model. The quality of evidence per association provided in meta-analyses was rated by the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) criteria as high, moderate, low, and very low. Results We included 17 meta-analyses comprising 68 RCTs (median [interquartile range, IQR] sample size of 42 [20–104] participants and follow-up period of 13 [8–36] weeks) and 115 unique associations. There were 51 statistically significant associations (44%) of which four associations were supported by high-quality evidence (reduced triglyceride ( n  = 2), seizure frequency ( n  = 1) and increased low-density lipoprotein cholesterol (LDL-C) ( n  = 1)) and four associations supported by moderate-quality evidence (decrease in body weight, respiratory exchange ratio (RER), hemoglobin A 1c , and increased total cholesterol). The remaining associations were supported by very low (26 associations) to low (17 associations) quality evidence. In overweight or obese adults, VLCKD was significantly associated with improvement in anthropometric and cardiometabolic outcomes without worsening muscle mass, LDL-C, and total cholesterol. K-LCHF was associated with reduced body weight and body fat percentage, but also reduced muscle mass in healthy participants. Conclusions This umbrella review found beneficial associations of KD supported by moderate to high-quality evidence on seizure and several cardiometabolic parameters. However, KD was associated with a clinically meaningful increase in LDL-C. Clinical trials with long-term follow-up are warranted to investigate whether the short-term effects of KD will translate to beneficial effects on clinical outcomes such as cardiovascular events and mortality.

Neglected tropical diseases (NTDs) mainly affect underprivileged populations, potentially resulting in catastrophic health spending (CHS) and impoverishment from out-of-pocket (OOP) costs. This systematic review aimed to summarize the financial hardship caused by NTDs. We searched PubMed, EMBASE, EconLit, OpenGrey, and EBSCO Open Dissertations, for articles reporting financial hardship caused by NTDs from database inception to January 1, 2023. We summarized the study findings and methodological characteristics. Meta-analyses were performed to pool the prevalence of CHS. Heterogeneity was evaluated using the I2 statistic. Ten out of 1,768 studies were included, assessing CHS (n = 10) and impoverishment (n = 1) among 2,761 patients with six NTDs (Buruli ulcer, chikungunya, dengue, visceral leishmaniasis, leprosy, and lymphatic filariasis). CHS was defined differently across studies. Prevalence of CHS due to OOP costs was relatively low among patients with leprosy (0.0-11.0%), dengue (12.5%), and lymphatic filariasis (0.0-23.0%), and relatively high among patients with Buruli ulcers (45.6%). Prevalence of CHS varied widely among patients with chikungunya (11.9-99.3%) and visceral leishmaniasis (24.6-91.8%). Meta-analysis showed that the pooled prevalence of CHS due to OOP costs of visceral leishmaniasis was 73% (95% CI; 65-80%, n = 2, I2 = 0.00%). Costs of visceral leishmaniasis impoverished 20-26% of the 61 households investigated, depending on the costs captured. The reported costs did not capture the financial burden hidden by the abandonment of seeking healthcare. NTDs lead to a substantial number of households facing financial hardship. However, financial hardship caused by NTDs was not comprehensively evaluated in the literature. To develop evidence-informed strategies to minimize the financial hardship caused by NTDs, studies should evaluate the factors contributing to financial hardship across household characteristics, disease stages, and treatment-seeking behaviors.

Despite domestic production of antivenoms in the Association of Southeast Asian Nations (ASEAN) countries, not all victims with snakebite envenomings indicated for antivenom received the appropriate or adequate effective dose of antivenom due to insufficient supply and inadequate access to antivenoms. We aimed to conduct a cost-effectiveness analysis to project the potential economic and clinical impact of improving access to antivenoms when all snakebite envenomings in ASEAN countries were hypothetically treated with geographically appropriate antivenoms. Using a decision analytic model with input parameters from published literature, local data, and expert opinion, we projected the impact of \"full access\" (100%) to antivenom, compared to \"current access\" in five most impacted ASEAN countries, including Indonesia (10%), Philippines (26%), Vietnam (37%), Lao PDR (4%), and Myanmar (64%), from a societal perspective with a lifetime time horizon. Sensitivity analyses were performed. In base-case analyses, full access compared to current access to snake antivenom in the five countries resulted in a total of 9,362 deaths averted (-59%), 230,075 disability-adjusted life years (DALYs) averted (-59%), and cost savings of 1.3 billion USD (-53%). Incremental cost-effectiveness ratios (ICERs) of improving access to antivenom found higher outcomes but lower costs in all countries. Probabilistic sensitivity analyses of 1,000 iterations found that 98.1-100% of ICERs were cost-saving. Improving access to snake antivenom will result in cost-saving for ASEAN countries. Our findings emphasized the importance of further strengthening regional cooperation, investment, and funding to improve the situation of snakebite victims in ASEAN countries.

Understanding the burden of snakebite is crucial for developing evidence-informed strategies to pursue the goal set by the World Health Organization to halve morbidity and mortality of snakebite by 2030. However, there was no such information in the Association of Southeast Asian Nations (ASEAN) countries. A decision analytic model was developed to estimate annual burden of snakebite in seven countries, including Malaysia, Thailand, Indonesia, Philippines, Vietnam, Lao PDR, and Myanmar. Country-specific input parameters were sought from published literature, country's Ministry of Health, local data, and expert opinion. Economic burden was estimated from the societal perspective. Costs were expressed in 2019 US Dollars (USD). Disease burden was estimated as disability-adjusted life years (DALYs). Probabilistic sensitivity analysis was performed to estimate a 95% credible interval (CrI). We estimated that annually there were 242,648 snakebite victims (95%CrI 209,810-291,023) of which 15,909 (95%CrI 7,592-33,949) were dead and 954 (95%CrI 383-1,797) were amputated. We estimated that 161,835 snakebite victims (69% of victims who were indicated for antivenom treatment) were not treated with antivenom. Annual disease burden of snakebite was estimated at 391,979 DALYs (95%CrI 187,261-836,559 DALYs) with total costs of 2.5 billion USD (95%CrI 1.2-5.4 billion USD) that were equivalent to 0.09% (95%CrI 0.04-0.20%) of the region's gross domestic product. >95% of the estimated burdens were attributed to premature deaths. The estimated high burden of snakebite in ASEAN was demonstrated despite the availability of domestically produced antivenoms. Most burdens were attributed to premature deaths from snakebite envenoming which suggested that the remarkably high burden of snakebite could be averted. We emphasized the importance of funding research to perform a comprehensive data collection on epidemiological and economic burden of snakebite to eventually reveal the true burden of snakebite in ASEAN and inform development of strategies to tackle the problem of snakebite.

Background: Access to high-cost cancer drugs is an unsolved problem globally. The dedicated drugs fund is attractive and feasible. This study reviewed currently implemented dedicated drugs fund worldwide to inform policy implications for Thailand. Methods: A scoping review was conducted to identify countries currently implementing dedicated funds for cancer drugs. We searched electronic databases, PubMed and Embase, from 2010 to May 2021, Google and Google Scholar in August 2021, and government websites up to April 2022. The structure, management, cost containment strategies, and impact of dedicated funds were summarized and compared across the identified countries and Thailand. Results: Out of 218 nations, Hong Kong, England, and Italy have established dedicated cancer drugs fund, primarily funded by their governments. Funds in England and Italy operate within annual budget limits. Hong Kong relies on an endowment fund. In England and Italy, pharmaceutical companies contribute proportionally to cover overspending as per risk-sharing agreements, while cost-sharing is not required. Hong Kong implements cost-sharing based on a patient's family income. England and Italy employ a parallel pathway, utilizing the same drug selection committee to determine whether innovative drugs belong in the regular pharmaceutical benefits package or the dedicated drugs fund. Hong Kong follows a sequential pathway, allowing drugs to be considered for the dedicated funds after a negative decision. These countries use the fund for 5-11 years, making administrative adjustments to ensure sustainability. Conclusion: The dedicated drugs fund is an effective strategy to improve access to non-reimbursable high-cost drugs in Thailand. Robust evaluation of the fund itself and funded drugs are recommended for policymakers’ better decision-making. Learning from other countries can offer promising solutions. Health insurers need to balance providing cancer treatments with overall system preparedness.

IntroductionCanine osteoarthritis (OA) is a degenerative disease with chronic inflammation of internal and external joint structures in dogs. Cannabis spp. contains cannabidiol (CBD), a substance known for various potential indications, such as pain relief and anti-inflammatory in various types of animals, including dogs with OA. As CBD is increasingly in the spotlight for medical use, we aimed to perform a systematic review and meta-analysis to evaluate the efficacy and safety of CBD in treating canine OA.MethodsWe searched PubMed, Embase, Scopus, and CAB Direct for animal intervention studies investigating the effects of CBD for canine OA from database inception until February 28, 2023. Study characteristics and findings were summarized. A risk of bias in the included studies was assessed. Meta-analyses were performed using a random-effects model to estimate the effects of CBD on pain scores (0–10), expressed as mean difference (MD) and 95% confidence interval (95% CI). Certainty of evidence was assessed using GRADE.ResultsFive articles were included, which investigated the effects of CBD in 117 dogs with OA. All studies were rated as having a high risk of bias. CBD products varied substantially, i.e., oral full-spectrum CBD oil in four studies, and isolated CBD oil and liposomal CBD oil in another study. Treatment duration varied from 4–12 weeks. Meta-analyses of three studies found that, in dogs with OA, treatment with oral full-spectrum CBD oil may reduce pain severity scores (MD; −0.60, 95% CI; −1.51 to 0.31, I 2 = 45.64%, p  = 0.19) and pain interference scores (MD; −1.52, 95% CI; −3.84 to 0.80, I 2 = 89.59%, p  = 0.20) but the certainty of evidence was very low. CBD is generally considered safe and well-tolerated in the short-run, with few mild adverse events observed, such as vomiting and asymptomatic increase in alkaline phosphatase level.ConclusionCBD is considered safe for treating canine OA. CBD may reduce pain scores, but the evidence is very uncertain to conclude its clinical efficacy. High-quality clinical trials are needed to further evaluate the roles of CBD in canine OA.

PurposeThis study explored health insurance coverage of genetic testing and potential factors associated with precision medicine (PM) reimbursement in Thailand.Design/methodology/approachThe study employed a targeted review method. Thirteen PMs were selected to represent four PM categories: targeted cancer therapy candidate, prediction of adverse drug reactions (ADRs), dose adjustment and cancer risk prediction. Content analysis was performed to compare access to PMs among three health insurance schemes in Thailand. The primary outcome of the study was evaluating PM test reimbursement status. Secondary outcomes included clinical practice guidelines, PMs statement in FDA-approved leaflet and economic evaluation.FindingsCivil Servant Medical Benefits Scheme (CSMBS) provided more generous access to PM than Universal Coverage Scheme (UCS) and Social Security Scheme (SSS). Evidence of economic evaluations likely impacted the reimbursement decisions of SSS and UCS, while the information provided in FDA-approved leaflets seemed to impact the reimbursement decisions of CSMBS. Three health insurance schemes provided adequate access to PM tests for some cancer-targeted therapies, while gaps existed for access to PM tests for serious ADRs prevention, dose adjustment and cancer risk prediction.Originality/valueThis was the first study to explore the situation of access to PMs in Thailand. The evidence alerts public health insurance schemes to reconsider access to PMs. Development of health technology assessment guidelines for PM test reimbursement decisions should be prioritized.

The Immunization Agenda 2030 prioritizes the populations without access to vaccines. Health equity has been increasingly incorporated into economic evaluations of vaccines to foster equitable access. Robust and standardized methods are needed to evaluate the health equity impact of vaccination programs to ensure monitoring and effective addressing of inequities. However, methods currently in place vary and potentially affect the application of findings to inform policy decision-making. We performed a systematic review by searching PubMed, Embase, Econlit, and the CEA Registry up to 15 December 2022 to identify equity-informative economic evaluations of vaccines. Twenty-one studies were included that performed health equity impact analysis to estimate the distributional impact of vaccines, such as deaths averted and financial risk protection, across equity-relevant subgroups. These studies showed that the introduction of vaccines or improved vaccination coverage resulted in fewer deaths and higher financial risk benefits in subpopulations with higher disease burdens and lower vaccination coverage—particularly poorer income groups and those living in rural areas. In conclusion, methods to incorporate equity have been evolving progressively. Vaccination programs can enhance equity if their design and implementation address existing inequities in order to provide equitable vaccination coverage and achieve health equity.

Snakebite envenoming, a high priority Neglected Tropical Disease categorized by the World Health Organization (WHO), has been considered as a poverty-related disease that requires greater global awareness and collaboration to establish strategies that effectively decrease economic burdens. This prompts the need for a comprehensive review of the global literature that summarizes the global economic burden and a description of methodology details and their variation. This study aimed to systematically identify studies on cost of illness and economic evaluation associated with snakebites, summarize study findings, and evaluate their methods to provide recommendations for future studies. We searched PubMed, EMBASE, Cochrane library, and Econlit for articles published from inception to 31 July 2019. Original articles reporting costs or full economic evaluation related with snakebites were included. The methods and reporting quality were assessed. Costs were presented in US dollars (US$) in 2018. Twenty-three cost of illness studies and three economic evaluation studies related to snakebites were included. Majority of studies (18/23, 78.26%) were conducted in Low- and Middle-income countries. Most cost of illness studies (82.61%) were done using hospital-based data of snakebite patients. While, four studies (17.39%) estimated costs of snakebites in communities. Five studies (21.74%) used societal perspective estimating both direct and indirect costs. Only one study (4.35%) undertook incidence-based approach to estimate lifetime costs. Only three studies (13.04%) estimated annual national economic burdens of snakebite which varied drastically from US$126 319 in Burkina Faso to US$13 802 550 in Sri Lanka. Quality of the cost of illness studies were varied and substantially under-reported. All three economic evaluation studies were cost-effectiveness analysis using decision tree model. Two of them assessed cost-effectiveness of having full access to antivenom and reported cost-effective findings. Economic burdens of snakebite were underestimated and not extensively studied. To accurately capture the economic burdens of snakebites at both the global and local level, hospital data should be collected along with community survey and economic burdens of snakebites should be estimated both in short-term and long-term period to incorporate the lifetime costs and productivity loss due to premature death, disability, and consequences of snakebites.

Background The use of pharmaceutical pictograms to enhance patients’ understanding of drug regimens has been proven effective in many countries. There are two reference systems for pictograms generally used in pharmacy: the United States Pharmacopeia (USP) and International Pharmacy Federation (FIP). This study aimed to evaluate the effectiveness of USP and FIP pictograms among adults in the Philippines by identifying how many pictograms would pass the American National Standards Institute (ANSI) criterion of 85% comprehension, and to describe the factors affecting pictograms’ comprehension. Methods A descriptive cross-sectional research using a face-to-face interview was performed to evaluate 108 pictograms in 52 Filipino adults enrolled through quota sampling. Descriptive statistics, Mann–Whitney U test (Wilcoxon rank-sum test), univariate linear regression, and multiple linear regression were used to statistically analyze the data collected. Results Only 17 (16 USP and 1 FIP) out of the 108 pictograms (15.74%) passed the ANSI criterion. The median score of Filipinos was 71 out of 108 pictograms (Interquartile range: 10–96). The multivariate model ( R 2  = 0.5645, F (4,47) = 15.23) suggested that the score was lower by 5.85 points if the user was female, 21.58 points lower if the participant was below Grade 12 education level, and 1.20 points lower if the patient was greater than 46 years old. Education level was identified as the significant predictor ( p -value < 0.0000*, power = 99.98%). The participant with greater than Grade 12 has a higher comprehension score of rank-sum 952.5 (Expected = 689) compared to only 425.5 (Expected = 689). Conclusions Since only 17 pictograms passed as stand-alone tool for patient information material, the researchers recommend the use of verbal and written instructions to complement pictograms to enhance comprehension. Furthermore, the government should consider the inclusion of health pictograms in basic health education.