Preclinical testing of expired antivenoms and its uses in real-world experience: a systematic review.

INTRODUCTION: Limited access to antivenoms is a global challenge in treating snakebite envenoming. In emergency situations where non-expired antivenoms are not readily available, expired antivenoms may be used to save lives with the risk of deteriorating quality, efficacy and safety. Therefore, we aimed to systematically review and summarise the sparse preclinical evidence of neutralising efficacy of expired antivenoms and real-world experience of using expired antivenoms in humans. METHODS: We searched for articles published until 1 March 2023 in PubMed, Scopus, Web of Science and Embase. Studies demonstrating the preclinical studies evaluating expired antivenoms or studies describing the real-world experience of using expired antivenoms were included. Narrative synthesis was applied to summarise the evidence of expired antivenoms. RESULTS: Fifteen studies were included. Ten were preclinical studies and five were real-world experiences of using expired antivenoms in humans. The expired duration of antivenoms in the included studies ranged from 2 months to 20 years. The quality of expired antivenoms was evaluated in one study, and they met the standard quality tests. Five studies demonstrated that the expired antivenoms' immunological concentration and venom-binding activity were comparable to non-expired ones but could gradually deteriorate after expiration. Studies consistently exhibited that expired antivenoms, compared with non-expired antivenoms, were effective when stored in proper storage conditions. The safety profile of using expired antivenoms was reported in two included studies. However, it was inconclusive due to limited information. CONCLUSION: Even though the quality and efficacy of expired antivenoms are comparable to non-expired antivenoms in preclinical studies, the information is limited in terms of real-world experiences of using expired antivenoms and their safety. Therefore, the use of expired antivenoms may be generally inconclusive due to scarce data. Further investigations may be needed to support the extension of antivenoms' expiration date according to their potential efficacy after expiration.

Financial hardship among patients suffering from neglected tropical diseases: A systematic review and meta-analysis of global literature.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Incremental net monetary benefit of using varenicline for smoking cessation: A systematic review and meta-analysis of economic evaluation studies.

AIMS: To conduct a systematic review and meta-analysis and pool the incremental net benefits (INBs) of varenicline compared with behaviour support with bupropion or nicotine replacement therapy (NRT), behaviour support alone and unaided cessation in adult smokers making a first-time attempt to quit. METHODS: A search for economic evaluation studies was conducted from inception to 30 September 2022, on PubMed, Embase, Cost-Effectiveness Analysis (CEA) Registry by Tufts Medical Centre, EconLit and the NHS Economic Evaluation Database (NHS EED). Eligible studies were included if they were (1) conducted among adults ages 18 years old and older who were smokers attempting to quit for the first time; (2) compared varenicline to behaviour support with bupropion or NRT, behaviour support alone and unaided cessation; and (3) performed a CEA or cost-utility analysis. The INBs were calculated and pooled across studies stratified by country income level and study perspective using the random-effects model. Statistical heterogeneity between studies was assessed using the I2 statistic and Cochrane Q statistic. RESULTS: Of the 1433 identified studies, 18 studies were included in our review. Our findings from healthcare system/payer perspective suggested that the use of varenicline is statistically significantly cost-effective compared with bupropion (pooled INB, $830.75 [95% confidence interval, $208.23, $1453.28]), NRTs ($636.16 [$192.48, $1079.84]) and unaided cessation ($4212.35 [$1755.79, $6668.92]) in high-income countries. Similarly, varenicline is also found to be cost-effective compared to bupropion ($2706.27 [$1284.44, $4128.11]), NRTs ($3310.01 [$1781.53, $4838.50]) and behavioural support alone ($5438.22 [$4105.99, $6770.46]) in low- and middle-income countries. CONCLUSION: Varenicline is cost-effective as a smoking cessation aid when compared with behavioural support with bupropion or nicotine replacement therapies and behavioural support alone in both high-income countries and low- and middle-income countries, from the healthcare system/payer perspective in adult smokers who attempt to quit for the first time.

The association of weight loss from anti-obesity medications or bariatric surgery and apnea-hypopnea index in obstructive sleep apnea.

INTRODUCTION: Weight loss is recommended for individuals with obstructive sleep apnea (OSA) and overweight or obesity, but there is limited evidence to guide the selection of weight management strategies for patients who do not lose sufficient weight with diet and lifestyle changes. We evaluated the relationship between weight loss caused by pharmacologic or surgical interventions and subsequent improvement in OSA by the apnea-hypopnea index (AHI). METHODS: PubMed, Cochrane CENTRAL, and EMBASE were searched for randomized trials comparing pharmacologic or surgical obesity interventions to usual care, placebo, or no treatment in adults with OSA. The association between percentage weight loss and AHI change between randomization and last follow-up was evaluated using meta-regression. PROSPERO: CRD42022378853. RESULTS: Ten eligible trials (n = 854 patients) were included. Four (n = 211) assessed bariatric surgery, and 6 (n = 643) assessed pharmacologic interventions over a median follow-up of 13 months (interquartile range 6-26 months). The linear best estimate of the change in AHI is 0.45 events per hour (95% Confidence Interval 0.18 to 0.73 events per hour) for every 1% body weight lost. CONCLUSIONS: Weight loss caused by medication or surgery caused a proportionate improvement of the AHI. Providers could consider extrapolating from this relationship when advising patients of the expected effects of other pharmacologic or surgical interventions without direct evidence in OSA.

Efficacy and safety of cannabidiol for the treatment of canine osteoarthritis: a systematic review and meta-analysis of animal intervention studies.

Introduction: Canine 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. Methods: We 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. Results: Five 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, I2 = 45.64%, p = 0.19) and pain interference scores (MD; -1.52, 95% CI; -3.84 to 0.80, I2 = 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. Conclusion: CBD 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.

A cost-effectiveness analysis of national smoking cessation services among chronic obstructive pulmonary disease patients in Thailand.

AIMS: Thailand's national smoking cessation services (FAH-SAI clinics) were founded in 2010. A cost-effectiveness analysis (CEA) is needed to inform policymakers of the allocation and prioritization of the limited budget to maximize the value for money of reimbursing these services. Chronic obstructive pulmonary disease (COPD) patients would benefit from smoking cessation services. Therefore, this study aimed to assess the cost-effectiveness of these multidisciplinary services compared to the usual care among COPD patients in Thailand from a societal perspective. METHODS: We conducted a CEA from a societal perspective using a Markov model to simulate lifetime costs and quality-adjusted life years (QALYs) gained by each smoking cessation intervention over the patient's lifetime. We derived the effectiveness of the smoking cessation services from a multicenter, longitudinal study of smoking cessation services in Thailand and estimated the natural quit rate, transition probabilities, health utility, and cost data from the published literature. Costs and outcomes were discounted at 3%. Sensitivity analyses were performed. RESULTS: Compared to the usual care, FAH-SAI clinics were associated with higher costs (4,207 THB (US$133)) and improved QALYs (0.11), with an incremental cost-effectiveness ratio of 37,675 THB/QALY (US$1,187/QALY). The effectiveness of FAH-SAI clinics was a key driver of the cost-effectiveness results. At the willingness-to-pay (WTP) threshold of 160,000 THB (US$5,042) per QALY gained, the probability of being cost-effective was 96.5%. CONCLUSIONS: FAH-SAI clinics were cost-effective under Thailand's WTP threshold. Our results could inform policymakers in allocating resources to support smoking cessation services for COPD patients in Thailand.

Antivenom preclinical efficacy testing against Asian snakes and their availability in Asia: A systematic review.

BACKGROUND: Cross-neutralizing strategy has been applied to improve access to antivenoms, a key to reducing mortality and disability of snakebite envenoming. However, preclinical studies have been conducted to identify antivenoms' cross-neutralizing ability when clinical studies may not be considered ethical. Therefore, this study aimed to identify and summarize scattered evidence regarding the preclinical efficacy of antivenoms against Asian snakes. METHODOLOGY/PRINCIPLE FINDINGS: In this systematic review, we searched for articles published until May 30, 2022, in PubMed, Scopus, Web of Science, and Embase. Preclinical studies that reported the available antivenoms' neutralizing ability against Asian snake lethality were included. Quality assessment was performed using the Systematic Review Centre for Laboratory animal Experimentation's risk of bias tool and the adapted the Animal Research Reporting In Vivo Experiments guidelines. The availability of effective antivenoms against Asian snakes was analyzed by comparing data from included studies with snakebite-information and data platforms developed by the World Health Organization. Fifty-two studies were included. Most studies assessed the antivenom efficacy against snakes from Southeast Asia (58%), followed by South Asia (35%) and East Asia (19%). Twenty-two (49%) medically important snakes had antivenom(s) with confirmed neutralizing ability. Situation analyses of the availability of effective antivenoms in Asia demonstrated that locally produced antivenoms did not cover all medically important snakes in each country. Among countries without local antivenom production, preclinical studies were conducted only in Bangladesh, Sri Lanka, and Malaysia. Risk of bias assessment was limited in some domains because of unreported data. CONCLUSIONS/SIGNIFICANCE: Cross-neutralizing of antivenoms against some medically important snakes in Asia was confirmed. This strategy may improve access to geographically effective antivenoms and bypass investment in novel antivenom development, especially in countries without local antivenom production. A database should be developed to aid the development of a snakebite-information system.

Economic and Clinical Outcomes of Pediatric Patients Under Two With Respiratory Syncytial Virus Infection in Thailand: A Real-world Retrospective Cohort Study.

BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of acute respiratory tract infection in children, including in Thailand. We conducted this study to evaluate the economic and clinical outcomes of patients <2 years old with RSV infection at a tertiary teaching hospital in Thailand. METHODS: This was a retrospective cohort study during 2014-2021. To be eligible, patients had to report at least 1 positive RSV test and were <2 years old. Descriptive statistics were used to describe baseline characteristics, healthcare resource utilization, direct medical costs (1 US dollars [USD] = 31.98 Thai Baht) and clinical outcomes. RESULTS: Among 1370 RSV-positive patients, 49.9% of the patients (n = 683) were hospitalized at or within 3 days of RSV diagnosis with a median length of stay of 6 days (interquartile range [IQR]: 4-9 days), 38.8% were diagnosed with RSV-related respiratory complications (n = 532) and 1.5% died during the hospitalization episode (n = 20). A total of 22.5% of hospitalized patients (n = 154) received critical care during the hospitalization episode. The median cost of each RSV episode was USD539 (IQR: USD167-USD2106) and was higher among hospitalized patients (median: USD2112; IQR: USD1379-USD3182) compared with nonhospitalized patients (median: USD167; IQR: USD112-USD276). CONCLUSIONS: RSV infection represents a potentially important contributor to healthcare resource use and medical costs among children <2 years old in Thailand. Coupled with epidemiologic data, findings from our study will be useful to illustrate the overall economic burden associated with RSV infection among children in Thailand.

Community Pharmacists' Experiences and Attitudes towards the Provision of Sexual and Reproductive Health Services: An International Survey.

Access to comprehensive sexual and reproductive health (SRH) services remains a challenge worldwide. Describing community pharmacists' SRH services in countries with different scopes of practice will aid in understanding how pharmacists view their roles and how to support them in providing needed services. A cross-sectional web-based survey was administered to pharmacists working in community pharmacies in Japan, Thailand, and Canada. The survey covered 7 SRH categories: pregnancy tests, ovulation tests, contraception, emergency contraception, sexually transmitted and blood-borne infections, maternal and perinatal health, and general sexual health. Descriptive statistics were used to analyze the data. A total of 922 eligible responses were included in the analysis (Japan = 534, Thailand = 85, and Canada = 303). Most Thai and Canadian participants reported dispensing hormonal contraceptives (Thailand = 99%, Canada = 98%) and emergency contraceptive pills (Thailand = 98%, Canada = 97%). Most Japanese participants provided patient education on barrier contraceptives for men (56%) and information on the safety of medications in pregnancy (74%) and breastfeeding (76%). The majority of participants expressed interest in additional training and expanding their roles in SRH. Sharing international experiences can guide challenges faced by the evolution of pharmacists' practice in SRH. Providing pharmacists support could help their readiness for this role.

Effects of ketogenic diet on health outcomes: an umbrella review of meta-analyses of randomized clinical trials.

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 A1c, 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.

Implementation challenges and real-world impacts of switching pediatric vaccines: A global systematic literature review.

Switching a vaccine for another on a pediatric national immunization program is often done for the betterment of society. However, if poorly implemented, switching vaccines could result in suboptimal transitions with negative effects. A systematic review was conducted to evaluate the existing knowledge from identifiable documents on implementation challenges of pediatric vaccine switches and the real-world impact of those challenges. Thirty-three studies met the inclusion criteria. We synthesized three themes: vaccine availability, vaccination program deployment, and vaccine acceptability. Switching pediatric vaccines can pose unforeseen challenges to health-care systems worldwide and additional resources are often required to overcome those challenges. Yet, the magnitude of the impact, especially economic and societal, was frequently under-researched with variability in reporting. Therefore, an efficient vaccine switch requires a thorough consideration of the added benefits of replacing the existing vaccine, preparation, planning, additional resource allocation, implementation timing, public-private partnerships, outreach campaigns, and surveillance for program evaluation.

Equity-Informative Economic Evaluations of Vaccines: A Systematic Literature Review.

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.

Thai veterinarians' perceptions of cannabidiol products for dogs with osteoarthritis: a qualitative interview study.

Introduction: The global popularity of cannabidiol (CBD) led to its approval for human use in Thailand and potential use in animals. Many studies revealed CBD's efficacy in treating chronic osteoarthritis (OA) in dogs. To facilitate tailored CBD product development for canine OA and ensure market success, this study explores Thai veterinarians' perception of CBD for canine OA. Methods: In-depth interviews were conducted with experienced veterinarians who treated OA in ≥25% of their canine patients. Interview questions covered treatment, CBD perception, and adoption. Interviews were held from January to March 2023. Results: Eleven out of twenty invited veterinarians participated in the study. Though all favored non-steroidal anti-inflammatory drugs (NSAIDs) for OA in dogs, concerns about adverse reactions, including ulcers and renal failure, emerged. CBD was widely known and was perceived positively for pain, inflammation, cancer, and epilepsy. However, half distinguished CBD from marijuana and tetrahydrocannabinol (THC). Ten expressed willingness to prescribe CBD for OA upon robust clinical evidence. Worries centered on product consistency and impurities. Many suggested CBD should be under veterinarians' supervision at first, but this can be relaxing once safety and efficacy are established. CBD products should be chewable tablets, oils, or gelatin capsules with flavors like beef, liver, pork, fish, or seafood. Conclusion: Though CBD benefits were recognized, knowledge gaps among the participants persisted, warranting robust CBD safety, efficacy, and quality evidence to ensure Thai market success. Comprehensive education, including continuing education for those in practice and incorporating CBD-related topics into the Schools of Veterinary's curriculum, is recommended.

Potential economic and clinical implications of improving access to snake antivenom in five ASEAN countries: A cost-effectiveness analysis.

BACKGROUND: 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. METHODOLOGY: 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. PRINCIPAL FINDINGS: 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. CONCLUSION/SIGNIFICANCE: 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.

Estimating economic and disease burden of snakebite in ASEAN countries using a decision analytic model.

BACKGROUND: 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. METHODOLOGY: 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). PRINCIPAL FINDINGS: 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. CONCLUSION/SIGNIFICANCE: 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.

Evaluation of pharmaceutical pictogram comprehension among adults in the Philippines.

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 (R2 = 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.

Situation of snakebite, antivenom market and access to antivenoms in ASEAN countries.

INTRODUCTION: Snakebite envenoming is a neglected tropical disease posing public health challenges globally. The Association of Southeast Asian Nations (ASEAN) countries are among the tropical regions with disproportionately high incidence of snakebite. Hence, this study aimed to review the situation of snakebite, antivenom market and access to antivenoms in ASEAN. METHODS: This mixed-methods study included comprehensive literature review and in-depth interviews with key informants to assess the situation of management system of snakebite, antivenom market and access to antivenoms in seven ASEAN countries, including Malaysia, Thailand, Indonesia, Philippines, Vietnam, Lao PDR and Myanmar. Data were analysed by a framework method. RESULTS: ASEAN have developed various strategies to improve outcomes of snakebite victims. Five domestic antivenom manufacturers in the region produce up to 288 375 vials of antivenoms annually with the value of US$13 058 053 million which could treat 42 213 snakebite victims. However, there remain challenges to be addressed especially the lack of snakebite-related informatics system, inadequate antivenoms at the healthcare facilities and when the majority of snakebite victims seek traditional healers instead of conventional treatment. CONCLUSION: Improving the situation of snakebite and antivenom is not only about the availability of antivenom, but the whole landscape of surrounding management and supporting system. The assessment of the situation of snakebite and antivenom is crucial for countries or regions where snakebites are prevalent to recognise their current standpoint to inform the development of strategies to achieve the goal set by the WHO of halving the global burden of snakebite by 2030.

Financing Strategies to Facilitate Access to High-Cost Anticancer Drugs: A Systematic Review of the Literature.

BACKGROUND: Each country manages access to anticancer drugs differently due to variations in the structure and financing of the health system, but a summary of the various strategies used is absent. This study aimed to review and summarize financing strategies implemented across countries to facilitate access to high-cost anticancer drugs. METHODS: We conducted a systematic review of articles referenced in PubMed, Embase, and Web of Science through May 12, 2021. Articles published in the English language from 2000 that describe strategies implemented in different countries to facilitate access to high-cost anticancer drugs were included. Letters, news articles, and proposed strategies were excluded. Quality assessment was not performed as we aimed to summarize the strategies. Data were analyzed by thematic analysis. A review protocol was registered at PROSPERO (CRD42018068616). RESULTS: The review included 204 studies from 176 countries. Three themes of financing strategies were identified: (1) Basic pharmaceutical reimbursement and pricing policies, (2) Alternative funding strategies specific to high-cost drugs, and (3) Financial assistance for individual patients. Access in most countries depends mainly on basic pharmaceutical reimbursement policies (165 of 176 countries). Apart from that, high-income countries (HICs) tended to use funding strategies targeting high-cost drugs (72% of HICs vs 0%-24% of the rest), such as managed entry agreements (MEAs) or dedicated funds for high-cost drugs. In contrast, lower-income countries tended to implement financial assistance programs for cancer patients as a tool to increase access (32% of HICs vs 62%-79% of the rest). CONCLUSION: Many countries have implemented a combination of strategies to increase access to high-cost anticancer drugs. Most low- and middle-income countries utilized placement of anticancer drugs on a national list of essential medicines and patient assistance programs (PAPs) to facilitate access, while many HICs implemented a broader range of strategies.

Intermittent Fasting and Obesity-Related Health Outcomes: An Umbrella Review of Meta-analyses of Randomized Clinical Trials.

Importance: Several meta-analyses of randomized clinical trials (RCTs) have demonstrated the many health benefits of intermittent fasting (IF). However, there has been little synthesis of the strength and quality of this evidence in aggregate to date. Objective: To grade the evidence from published meta-analyses of RCTs that assessed the associations of IF (zero-calorie alternate-day fasting, modified alternate-day fasting, the 5:2 diet, and time-restricted eating) with obesity-related health outcomes. Evidence Review: PubMed, Embase, and Cochrane database of systematic reviews were searched from database inception to January 12, 2021. Data analysis was conducted from April 2021 through July 2021. Meta-analyses of RCTs investigating effects of IF in adults were included. The effect sizes of IF were recalculated using a random-effects model. We assessed the quality of evidence per association by applying the GRADE criteria (Grading of Recommendations, Assessment, Development, and Evaluations) as high, moderate, low, and very low. Findings: A total of 11 meta-analyses comprising 130 RCTs (median [IQR] sample size, 38 [24-69] participants; median [IQR] follow-up period, 3 [2-5] months) were included describing 104 unique associations of different types of IF with obesity-related health outcomes (median [IQR] studies per association, 4 [3-5]). There were 28 statistically significant associations (27%) that demonstrated the beneficial outcomes for body mass index, body weight, fat mass, low-density lipoprotein cholesterol, total cholesterol, triglycerides, fasting plasma glucose, fasting insulin, homeostatic model assessment of insulin resistance, and blood pressure. IF was found to be associated with reduced fat-free mass. One significant association (1%) supported by high-quality evidence was modified alternate-day fasting for 1 to 2 months, which was associated with moderate reduction in body mass index in healthy adults and adults with overweight, obesity, or nonalcoholic fatty liver disease compared with regular diet. Six associations (6%) were supported by moderate quality evidence. The remaining associations found to be significant were supported by very low (75 associations [72%]) to low (22 associations [21%]) quality evidence. Conclusions and Relevance: In this umbrella review, we found beneficial associations of IF with anthropometric and cardiometabolic outcomes supported by moderate to high quality of evidence, which supports the role of IF, especially modified alternate-day fasting, as a weight loss approach for adults with overweight or obesity. More clinical trials with long-term follow-up are needed to investigate the effects of IF on clinical outcomes such as cardiovascular events and mortality.

Reproductive Health Services: Attitudes and Practice of Japanese Community Pharmacists.

The provision of sexual and reproductive health (SRH) services is an important part of a community pharmacist's role in many countries. However, such services are not traditionally provided by pharmacists in Japan. We surveyed the practice and attitudes regarding the provision of SRH services among Japanese community pharmacists with a focus on reproductive health (RH) topics. The participants were asked about the provision of RH services, attitudes toward their role as SRH providers, and self-reported confidence in providing education to patients on RH topics. We obtained 534 effective responses. About half of the participants reported providing RH services, and only 21% were involved in dispensing emergency contraception pills. Although the proportion of pharmacists providing education on these topics was considerably lower, about 80% recognized the importance of their role as SRH advisors. Confidence in providing patient education about RH topics depended on their experience in providing such services. Most participants were interested in additional SRH training (80%). Our results suggest that training programs could help to expand Japanese community pharmacists' roles as SRH providers and increase their confidence in the education of patients. This study provides useful insights to expand pharmacists' roles in Japan as providers of comprehensive SRH services.