Search

Abstract Background Globally, herpes simplex virus (HSV)-2 and -1 infections contribute to a large disease burden, but their full economic consequences remain unclear. This study aims to estimate the global economic impact of genital HSV-2 and HSV-1 infection and its consequences for people with genital ulcer disease, neonatal herpes, and human immunodeficiency virus (HIV) infection attributable to HSV-2. Methods Using a societal perspective, the economic burden was calculated at the country level and presented by World Health Organization (WHO) regions and World-Bank income levels. The disease burden was obtained from previously published global disease burden studies in 2016 and disaggregated for 194 countries. Estimates of healthcare resource utilisation were sourced from a literature review, and online interviews were conducted with 20 experts from all 6 WHO regions. Relevant costs were obtained from the literature and estimated in 2016 international dollars (I$). Results Both genital HSV-2 (I$31·2 billion) and HSV-1 (I$4·0 billion) infections and their consequences were estimated to cost I$35·3 billion globally in 2016. The major economic burden was from the Americas and Western Pacific regions combined, accounting for almost two-thirds of the global burden (I$20·8 billion). High- and upper-middle-income countries bore a large proportion of the economic burden (76·6% or I$27·0 billion). Costs were driven by the large number of HSV-2 recurrences; however, even assuming conservatively that people with symptomatic herpes have on average only one episode a year, global costs were estimated at I$16·5 billion. Conclusions The global costs of genital HSV infection and its consequences are substantial. HSV prevention interventions have the potential to avert a large economic burden in addition to disease burden; thus, efforts to accelerate HSV vaccine development are crucial.

Summary: During COVID-19 in the US, social determinants of health (SDH) have driven health disparities. However, the use of SDH in COVID-19 vaccine modeling is unclear. This review aimed to summarize the current landscape of incorporating SDH into COVID-19 vaccine transmission modeling in the US. Medline and Embase were searched up to October 2022. We included studies that used transmission modeling to assess the effects of COVID-19 vaccine strategies in the US. Studies’ characteristics, factors incorporated into models, and approaches to incorporate these factors were extracted. Ninety-two studies were included. Of these, 11 studies incorporated SDH factors (alone or combined with demographic factors). Various sets of SDH factors were integrated, with occupation being the most common (8 studies), followed by geographical location (5 studies). The results show that few studies incorporate SDHs into their models, highlighting the need for research on SDH impact and approaches to incorporating SDH into modeling. Funding: This research was funded by the Centers for Disease Control and Prevention (CDC).

IntroductionNeglected 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.MethodsWe 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.ResultsTen 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.ConclusionNTDs 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.

Background & Aims: Alcohol-associated liver diseases (ALDs) and alcohol use disorder (AUD) pose a global health risk. AUD is underrecognized in the elderly, and the burden of AUD complications, including ALD, may increase with aging populations and rising alcohol intake. However, there is a lack of epidemiological evidence on AUD and ALD in the elderly. Methods: Using the Global Burden of Disease Study 2019, we analyzed the prevalence, mortality, disability-adjusted life years (DALYs), age-standardized rates (ASRs), and temporal change from 2000 to 2019 of ALD and AUD in the overall population and the elderly (65–89 years). The findings were categorized by sex, region, nation, and sociodemographic index. Results: The prevalence rates of ALD in the elderly were higher than those in adolescents and young adults, whereas AUD levels were lower than those in adolescents and young adults. In 2019, there were 9.39 million cases (8.69% of cases in the overall population) of AUD, 3.23 million cases (21.8% of cases in the overall population) of alcohol-associated cirrhosis, and 68,468 cases (51.27% of cases in the overall population) of liver cancer from alcohol among the elderly. ASRs of the prevalence of ALD and AUD in the elderly increased in most regions; on the contrary, ASRs of death and DALYs decreased in most regions. Nevertheless, ASRs of death and DALYs from liver cancer from alcohol increased in many areas. Conclusions: Our findings highlighted the increased prevalence of ALD in the elderly, with a burden of AUD comparable with that in the overall population. Public health strategies on ALD and AUD targeting the elderly are urgently needed. Impact and implications: The burden of alcohol-associated liver disease (ALD) and alcohol use disorder (AUD) is increasing. Advances in healthcare and education have resulted in a remarkable spike in life expectancy and a consequential population aging. Nevertheless, little is known about the epidemiology of ALD and AUD in the elderly. Our study indicates the increasing burden of ALD and AUD in the elderly population, necessitating early detection, intervention, and tailored care to the unique needs and complexities faced by older individuals grappling with these conditions.

Abstract Anti-tuberculosis drug induced liver injury (Anti-TB DILI) is the most common adverse events (AEs) necessitating therapy interruption but there is no preventing regimen. This study aimed to examine the efficacy and safety of herbs/alternative medicines for preventing anti-TB DILI. Relevant articles were identified through a systematic search in 5 international databases from inception till March 2022. All randomized controlled trials (RCT) assessing the effects of herbal or alternative medicines against anti-TB DILI were included. The network meta-analysis (NMA) was used to synthesize the evidence for preventing hepatotoxicity using a random-effects model. A total of 3423 patients from 14 RCTs were included. The NMA indicated that supplementation of Turmeric plus Tinospora cordifolia (RR 0.07; 95% CI 0.02 to 0.28), and N-acetyl cysteine (NAC) (RR 0.09; 95% CI 0.01 to 0.75) significantly reduced the incidence of anti-TB DILI compared with placebo. In addition, poly herbal product significantly reduced alkaline phosphatase (ALP) (MD − 21.80; 95% CI − 33.80 to − 9.80) and total bilirubin (Tbil) compared with placebo (MD − 0.51; 95% CI − 0.76 to − 0.26). There was no statistically significant difference in the occurrence of AEs in any intervention. In conclusion, Turmeric plus Tinospora cordifolia, NAC and poly-herbal product may provide benefit for preventing anti-TB DILI in TB patients. However, these findings are based on a small number of studies. Additional studies are warranted to confirm the findings.

Background/Objective: Clostridioides difficile infection (CDI) is a common healthcare-associated ailment, presenting major health and economic challenges, especially for the elderly. Despite its prevalence, comprehensive data about CDI’s impact on the elderly are limited. Methods: This study used the Global Burden of Disease Study 2019 data to analyze CDI trends from 2000 to 2019, considering factors like sex, region, and sociodemographic index (SDI). Results: This study revealed that CDI caused approximately 18,181 deaths and 252,709 disability-adjusted life years (DALYs) among the elderly worldwide. The Americas showed the highest CDI burden, while the Eastern Mediterranean saw the steepest rate increase from 2000 to 2019. Regions with a high SDI also displayed substantial CDI impact. Conclusions: The escalating burden of CDI in the elderly, especially in high-SDI areas and the Americas, emphasizes an urgent need for targeted public health strategies.

IntroductionServices to treat problematic alcohol use (PAU) should be highly accessible to optimize treatment engagement. We conducted a scoping review to map characteristics of services for the treatment of PAU that have been reported in the literature to be barriers to or facilitators of access to treatment from the perspective of individuals with PAU.MethodsA protocol was developed a priori, registered, and published. We searched MEDLINE®, Embase, the Cochrane Library, and additional grey literature sources from 2010 to April 2022 to identify primary qualitative research and surveys of adults with current or past PAU requiring treatment that were designed to identify modifiable characteristics of PAU treatment services (including psychosocial and pharmacologic interventions) that were perceived to be barriers to or facilitators of access to treatment. Studies of concurrent PAU and other substance use disorders were excluded. Study selection was performed by multiple review team members. Emergent barriers were coded and mapped to the accessibility dimensions of the Levesque framework of healthcare access, then descriptively summarized.ResultsOne-hundred-and-nine included studies reported an extensive array of unique service-level barriers that could act alone or together to prevent treatment accessibility. These included but were not limited to lack of an obvious entry point, complexity of the care pathway, high financial cost, unacceptably long wait times, lack of geographically accessible treatment, inconvenient appointment hours, poor cultural/demographic sensitivity, lack of anonymity/privacy, lack of services to treat concurrent PAU and mental health problems.DiscussionBarriers generally aligned with recent reviews of the substance use disorder literature. Ranking of barriers may be explored in a future discrete choice experiment of PAU service users. The rich qualitative findings of this review may support the design of new or modification of existing services for people with PAU to improve accessibility.Systematic Review RegistrationOpen Science Framework doi: 10.17605/OSF.IO/S849R.

Abstract 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

Abstract 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.

Introduction The SMART Quit Clinic Program (FAHSAI Clinic) has been implemented in Thailand since 2010; however, it remains unclear whether the benefits gained from this program justify its costs. We assessed its cost-effectiveness compared to usual care in a population of Thai smokers with cardiovascular disease (CVD) from a societal perspective. Methods We conducted a cost-utility analysis using a Markov model to simulate lifetime costs and quality-adjusted life years (QALYs) of Thai smokers aged ≥35 years receiving smoking cessation services offered from FAHSAI Clinic or usual care over a horizon of 50 years. The model used a 6-month continuous abstinence rate from a multicenter prospective study of 24 FAHSAI Clinics. A series of sensitivity analyses including probabilistic sensitivity analysis were conducted to assess robustness of study findings. Cost data are presented in US$ for 2020. Results The FAHSAI Clinic was dominant as it was less costly ($9537.92 vs $10964.19) and more effective (6.06 vs 5.96 QALYs) compared with usual care over the 50-year time horizon. Changes in risks of stroke and coronary heart disease among males had the largest impact on the cost-effectiveness findings. The probability that FAHSAI Clinic was cost-effective was 99.8% at a willingness-to- pay threshold of $5120. Conclusions The FAHSAI Clinic smoking cessation program was clinically superior and cost-saving compared to usual care for Thai patients with CVD in all scenarios. A budget impact analysis is needed to estimate the financial impact of adopting this program within the Thai healthcare system.

Background Studies assessing the indirect impact of COVID-19 using mathematical models have increased in recent years. This scoping review aims to identify modelling studies assessing the potential impact of disruptions to essential health services caused by COVID-19 and to summarise the characteristics of disruption and the models used to assess the disruptions.Methods Eligible studies were included if they used any models to assess the impact of COVID-19 disruptions on any health services. Articles published from January 2020 to December 2022 were identified from PubMed, Embase and CINAHL, using detailed searches with key concepts including COVID-19, modelling and healthcare disruptions. Two reviewers independently extracted the data in four domains. A descriptive analysis of the included studies was performed under the format of a narrative report.Results This scoping review has identified a total of 52 modelling studies that employed several models (n=116) to assess the potential impact of disruptions to essential health services. The majority of the models were simulation models (n=86; 74.1%). Studies covered a wide range of health conditions from infectious diseases to non-communicable diseases. COVID-19 has been reported to disrupt supply of health services, demand for health services and social change affecting factors that influence health. The most common outcomes reported in the studies were clinical outcomes such as mortality and morbidity. Twenty-five studies modelled various mitigation strategies; maintaining critical services by ensuring resources and access to services are found to be a priority for reducing the overall impact.Conclusion A number of models were used to assess the potential impact of disruptions to essential health services on various outcomes. There is a need for collaboration among stakeholders to enhance the usefulness of any modelling. Future studies should consider disparity issues for more comprehensive findings that could ultimately facilitate policy decision-making to maximise benefits to all.

BackgroundMeta-analyses have investigated associations between race and ethnicity and COVID-19 outcomes. However, there is uncertainty about these associations’ existence, magnitude, and level of evidence. We, therefore, aimed to synthesize, quantify, and grade the strength of evidence of race and ethnicity and COVID-19 outcomes in the US.MethodsIn this umbrella review, we searched four databases (Pubmed, Embase, the Cochrane Database of Systematic Reviews, and Epistemonikos) from database inception to April 2022. The methodological quality of each meta-analysis was assessed using the Assessment of Multiple Systematic Reviews, version 2 (AMSTAR-2). The strength of evidence of the associations between race and ethnicity with outcomes was ranked according to established criteria as convincing, highly suggestive, suggestive, weak, or non-significant. The study protocol was registered with PROSPERO, CRD42022336805.ResultsOf 880 records screened, we selected seven meta-analyses for evidence synthesis, with 42 associations examined. Overall, 10 of 42 associations were statistically significant (p ≤ 0.05). Two associations were highly suggestive, two were suggestive, and two were weak, whereas the remaining 32 associations were non-significant. The risk of COVID-19 infection was higher in Black individuals compared to White individuals (risk ratio, 2.08, 95% Confidence Interval (CI), 1.60–2.71), which was supported by highly suggestive evidence; with the conservative estimates from the sensitivity analyses, this association remained suggestive. Among those infected with COVID-19, Hispanic individuals had a higher risk of COVID-19 hospitalization than non-Hispanic White individuals (odds ratio, 2.08, 95% CI, 1.60–2.70) with highly suggestive evidence which remained after sensitivity analyses.ConclusionIndividuals of Black and Hispanic groups had a higher risk of COVID-19 infection and hospitalization compared to their White counterparts. These associations of race and ethnicity and COVID-19 outcomes existed more obviously in the pre-hospitalization stage. More consideration should be given in this stage for addressing health inequity.

ABSTRACTIntroduction Pneumococcal infections can lead to serious invasive diseases such as meningitis, septicemia and pneumonia, as well as milder but more common illnesses such as sinusitis and otitis media. The World Health Organization (WHO) recommends the inclusion of pneumococcal conjugate vaccines (PCVs) in infant National Immunization Program (NIP) programs worldwide. Decision-makers in Asian countries planning to introduce PCVs in their respective NIP will need a comprehensive evidence of effectiveness of PCVs at the population level and economic evidence including cost-effectiveness.Areas Covered A systematic literature review (from 1/1/2016 to 10/11/2019) of PCVs in East and Southeast Asia to understand (1) the contributing factors to cost-effectiveness results of PCVs and (2) whether gaps in evidence exist suggesting why the region may have yet to implement full NIPs.Expert Opinion In East and Southeast Asia, vaccination with PCVs was found to significantly reduce the mortality and morbidity of pneumococcal diseases and was cost-effective compared to no vaccination. Study assumptions, specifically vaccine local acquisition, the inclusion or exclusion of indirect effects (serotype replacement and herd effect), cross-protection, and protection against nontypeable haemophilus influenzae and serotype 3, were the main drivers of cost-effectiveness.

Abstract Background Asymptomatic hyperuricemia was found to be associated with increased cardiovascular disease risk but the potential benefits of urate-lowering therapy (ULT) remain controversial. We conducted a systematic review and network meta-analysis (NMA) with frequentist model to estimate the efficacy and safety of ULT in asymptomatic hyperuricemia. Methods MEDLINE, Embase, and Scopus were searched without language restrictions. Randomized controlled trials (RCT) of adults with asymptomatic hyperuricemia were eligible if they compared any pair of ULTs (i.e., allopurinol, febuxostat, probenecid, benzbromarone, sulfinpyrazone, rasburicase, lesinurad, and topiroxostat) and placebo or no ULT, and had outcomes of interest, including composite renal events, major adverse cardiovascular events, serum urate levels, estimated glomerular filtration rate (eGFR), systolic blood pressure, and adverse events. Results NMA with frequentist approach was applied to estimate relative treatment effects, i.e., risk ratio (RR) and mean difference (MD). A total of 23 RCTs were eligible. NMA identified beneficial effects of ULT on composite renal events and eGFR but not for other outcomes. Allopurinol and febuxostat had significantly lower composite renal events than placebo (RR 0.39, 95% confidence interval [CI] 0.23 to 0.66, and RR 0.68, 95% CI 0.46 to 0.99, respectively). Both treatments also resulted in significantly higher eGFR than placebo (MD 3.69 ml/min/1.73 m2, 95% CI 1.31 to 6.08, and MD 2.89 ml/min/1.73 m2, 95% CI 0.69 to 5.09, respectively). No evidence of inconsistency was identified. Conclusions Evidence suggests that allopurinol and febuxostat are the ULTs of choice in reducing composite renal events and improving renal function. Trial registration. This study was registered with PROSPERO: CRD42019145908. The date of the first registration was 12th November 2019.

This study conducted a cost–utility analysis and a budget impact analysis (BIA) of outpatient oral chemotherapy versus inpatient intravenous chemotherapy for stage III colorectal cancer (CRC) in Thailand. A Markov model was constructed to estimate the lifetime cost and health outcomes based on a societal perspective. Eight chemotherapy strategies were compared. Clinical and cost data on adjuvant chemotherapy were collected from the medical records of 1747 patients at Siriraj Hospital, Thailand. The cost-effectiveness results were interpreted against a Thai willingness-to-pay threshold of USD 5003/quality-adjusted life year (QALY) gained. A 5-year BIA was performed. Of the eight strategies, CAPOX then FOLFIRI yielded the highest life-year and QALY gains. Its total lifetime cost was also the highest. An incremental cost-effectiveness ratio of CAPOX then FOLFIRI compared to 5FU/LV then FOLFOX, a commonly used regimen USD was 4258 per QALY gained.The BIA showed that when generic drug prices were applied, 5-FU/LV then FOLFOX had the smallest budgetary impact (USD 9.1 million). CAPOX then FOLFIRI required an approximately three times higher budgetary level (USD 25.1 million). CAPOX then FOLFIRI is the best option. It is cost-effective compared with 5-FU/LV then FOLFOX. However, policymakers should consider the relatively high budgetary burden of the CAPOX then FOLFIRI regimen.

Nonalcoholic fatty liver disease (NAFLD) represents a significant health threat worldwide. The aging population and a rise in metabolic syndrome in Asia might influence the epidemiology of NAFLD among the elderly. However, there is a lack of understanding of the burden and recommendations for NAFLD in this group. Our study sought to investigate the trends in the NAFLD burden among the elderly in the Asia-Pacific region. We employed data from the Global Burden of Disease 2019 study for an in-depth analysis of the prevalence and disability-adjusted life years (DALYs) along with age-standardized rate (ASR) associated with NAFLD in elderly populations (age 65–89 years) across the Asia-Pacific region, including the Southeast Asia (SEA) and Western Pacific (WP) regions, from 2010 to 2019. This study also examined the trends and disparities in NAFLD burden across different nations and sexes. In 2019, there were over 120 million cases of NAFLD in the elderly in the Asia-Pacific region. The ASR of prevalence was higher in SEA compared to WP (36,995.37 vs. 32,821.78 per 100,000). ASR of prevalence increased with annual percentage change (APC) +0.95% in the WP while it increased by +0.87% in SEA. During the study period, the ASR of DALYs decreased in SEA (APC −0.41%) but remained stable in the WP region. The burden of NAFLD in the elderly population in Asia-Pacific has increased, underscoring the timely intervention to tackle this high and rising burden.

Background: Evidence has shown the positive impact of pharmacist involvement on the adherence and health outcomes of people living with HIV/AIDS. However, whether such intervention provides value for money remains unclear. This study aims to fill this gap by assessing the cost–effectiveness of pharmacist interventions in HIV care in Pakistan. Methods: A Markov decision analytic model was constructed, considering clinical inputs, utility data, and cost data obtained from a randomized controlled trial and an HIV cohort of Pakistani origin. The analysis was conducted from a healthcare perspective, and the incremental cost–effectiveness ratio (ICER) was calculated and presented for the year 2023. Additionally, a series of sensitivity analyses were performed to assess the robustness of the results. Results: Pharmacist intervention resulted in higher quality-adjusted life years (4.05 vs. 2.93) and likewise higher annual intervention costs than usual care (1979 USD vs. 429 USD) (532,894 PKR vs. 115,518 PKR). This yielded the ICER of 1383 USD/quality-adjusted life years (QALY) (372,406 PKR/QALY), which is well below the willingness-to-pay threshold of 1658 USD (446,456 PKR/QALY) recommended by the World Health Organization Choosing Interventions that are Cost-Effective. Probabilistic sensitivity analysis reported that more than 68% of iterations were below the lower limit of threshold. Sensitivity analysis reported intervention cost is the most important parameter influencing the ICER the most. Conclusion: The study suggests that involving pharmacists in HIV care could be a cost-effective approach. These findings could help shape healthcare policies and plans, possibly making pharmacist interventions a regular part of care for people with HIV in Pakistan.

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.

AimFasting Plasma Glucose (FPG) and Hemoglobin A1c (HbA1c) are used as diagnostic tests for diagnosing diabetes mellitus, but it is unclear which test has the best diagnostic accuracy. This systematic review and network meta-analysis aimed to estimate the diagnostic accuracy of HbA1c ≥ 6.5%, FPG ≥ 126 mg/dl, and the combination of HbA1c ≥ 6.5% or FPG ≥ 126 mg/dl (HbA1c| FPG), compared with Oral Glucose Tolerance Test (OGTT) ≥ 200 mg/dl for diagnosis diabetes.Materials and methodsWe performed a comprehensive search in PubMed, Embase, Cochrane Library, and Scopus from inception to September 24th, 2021. Inclusion criteria were any study design comparing HbA1c ≥ 6.5%, FPG ≥ 126 mg/dl, and HbA1c ≥ 6.5% or FPG ≥ 126 mg/dl with OGTT ≥ 200 mg/dl as the reference test. Data were independently extracted, risk of bias was assessed using QUADAS-2 by two reviewers. Network meta-analysis was done using a bivariate regression model using the Bayesian framework. The relative ranking of all tests was also assessed.ResultsOut of 5,026 studies, 73 were included. The sensitivities of HbA1c, FPG, and HbA1c| FPG were 0.51 [95% Credible Interval (CrI): 0.43, 0.58], 0.49 (95% CrI: 0.43, 0.55), and 0.64 (95% CrI: 0.51, 0.75), while the specificities were 0.96 (95% CrI: 0.94, 0.97), 0.98 (95% CrI: 0.97, 0.98), and 0.95 (95% CrI: 0.88, 0.98), respectively. The corresponding positive likelihood ratios (LR) were 13.36 (95% CrI: 8.91, 20.72), 21.94 (95% CrI: 15.04, 31.88), and 11.78 (95% CrI: 5.48, 26.56). HbA1c| FPG is superior based on sensitivity, whereas FPG is ranked best based on specificity and positive LR.ConclusionOur findings suggest that FPG ≥ 126 mg/dl should be recommended as the best diagnostic test for diabetes.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42021282856.

Ellagitannin-rich food has been implicated to ameliorate cardiovascular risk, particularly blood pressure (BP). This systematic review and meta-analysis investigated the effect of ellagitannin-rich fruit consumption on BP. Five databases were screened and RCTs reporting the effect of ellagitannin-rich fruit consumption on BP and polyphenol content were included. Nineteen studies with 1,249 participants, showed a non-significant systolic blood pressure (SBP) and significant diastolic blood pressure (DBP) reduction, with ET-rich fruit consumption. Subgroup analysis revealed significant SBP reduction among hypertensives receiving 500–1000 mg polyphenol (-4.95 mmHg, 95 % CI: [-7.24, −2.66]) and among metabolic syndrome (MS) patients (-3.44 mmHg; 95 % CI: [-5.25, −1.63]). meta-regression revealed a positive association between polyphenol dosage and SBP changes. In conclusion, the consumption of ellagitannin-rich fruits may be considered an anti-hypertensive functional food/drink and recommended for patients who are at high risk for hypertension. Further well-designed trials are required to resolve the significant heterogeneities identified in the current literature.

Health economic evaluations are comparative analyses of alternative courses of action in terms of their costs and consequences. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement, published in 2013, was created to ensure health economic evaluations are identifiable, interpretable, and useful for decision making. It was intended as guidance to help authors report accurately which health interventions were being compared and in what context, how the evaluation was undertaken, what the findings were, and other details that may aid readers and reviewers in interpretation and use of the study. The new CHEERS 2022 statement replaces previous CHEERS reporting guidance. It reflects the need for guidance that can be more easily applied to all types of health economic evaluation, new methods and developments in the field, as well as the increased role of stakeholder involvement including patients and the public. It is also broadly applicable to any form of intervention intended to improve the health of individuals or the population, whether simple or complex, and without regard to context (such as health care, public health, education, social care, etc). This summary article presents the new CHEERS 2022 28-item checklist and recommendations for each item. The CHEERS 2022 statement is primarily intended for researchers reporting economic evaluations for peer reviewed journals as well as the peer reviewers and editors assessing them for publication. However, we anticipate familiarity with reporting requirements will be useful for analysts when planning studies. It may also be useful for health technology assessment bodies seeking guidance on reporting, as there is an increasing emphasis on transparency in decision making.

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

Abstract Introduction There is increasing evidence that COVID-19 has unmasked the true magnitude of health inequity worldwide. Policies and guidance for containing the infection and reducing the COVID-19 related deaths have proven to be effective, however the extent to which health inequity factors were considered in these policies is rather unknown. The aim of this study is to measure the extent to which COVID-19 related policies reflect equity considerations by focusing on the global policy landscape around wearing masks and personal protection equipment (PPE). Methods A systematic search for published documents on COVID-19 and masks/PPE was conducted across six databases: PubMed, EMBASE, CINAHL, ERIC, ASSIA and Psycinfo. Reviews, policy documents, briefs related to COVID-19 and masks/PPE were included in the review. To assess the extent of incorporation of equity in the policy documents, a guidance framework known as ‘PROGRESS-Plus’: Place of residence, Race/ethnicity, Occupation, Gender/sex, Religion, Education, Socioeconomic status, Social capital, Plus (age, disability etc.) was utilized. Results This review included 212 policy documents. Out of 212 policy documents, 190 policy documents (89.62%) included at least one PROGRESS-plus component. Most of the policy documents (n = 163, 85.79%) focused on “occupation” component of the PROGRESS-plus followed by personal characteristics associated with discrimination (n = 4;2.11%), place of residence (n = 2;1.05%) and education (n = 1;0.53%). Subgroup analysis revealed that most of the policy documents (n = 176, 83.01%) were focused on “workers” such as healthcare workers, mortuary workers, school workers, transportation workers, essential workers etc. Of the remaining policy documents, most were targeted towards whole population (n = 30; 14.15%). Contrary to “worker focused” policy documents, most of the ‘whole population focused’ policy documents didn’t have a PROGRESS-plus equity component rendering them equity limiting for the society. Conclusion Our review highlights even if policies considered health inequity during the design/implementation, this consideration was often one dimensional in nature. In addition, population wide policies should be carefully designed and implemented after identifying relevant equity related barriers in order to produce better outcomes for the whole society.

The COVID-19 pandemic has had a dramatic impact on society, but little is known about how the pandemic affects the vaccine policy landscape and public perception of vaccines in Thailand. This study aims to describe potential changes in Thailand’s policy landscape post-pandemic. We performed a literature review and in-depth interviews with 12 key informants to understand the policy landscape in Thailand. The findings were shared in a policy forum in December 2021. Several key findings were summarized. Funding and development have been thriving during the pandemic. However, a long-term commitment from all stakeholders is required to maintain policy continuation. A public-private partnership should be considered. The regulatory body needs to be prepared for product authorization. The vaccine introduction decision-making process, and investment in prevention and promotion, should further be discussed. In summary, it is important to reshape the environment and mentality of all stakeholders to create a sustainable and self-sufficient vaccine ecosystem.

BackgroundDespite 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.MethodologyUsing 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 findingsIn 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/significanceImproving 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.

Introduction Prior to the COVID-19 pandemic, substance use health services for treatment of alcohol use disorder and problematic alcohol use (AUD/PAU) were fragmented and challenging to access. The pandemic magnified system weaknesses, often resulting in disruptions of treatment as alcohol use during the pandemic rose. When treatment services were available, utilisation was often low for various reasons. Virtual care was implemented to offset the drop in in-person care, however accessibility was not universal. Identification of the characteristics of treatment services for AUD/PAU that impact accessibility, as perceived by the individuals accessing or providing the services, will provide insights to enable improved access. We will perform a scoping review that will identify characteristics of services for treatment of AUD/PAU that have been identified as barriers to or facilitators of service access from the perspectives of these groups.Methods and analysis We will follow scoping review methodological guidance from the Joanna Briggs Institute. Using the OVID platform, we will search Ovid MEDLINE including Epub Ahead of Print and In-Process and Other Non-Indexed Citations, Embase Classic+Embase, APA PsychInfo, Cochrane Register of Controlled Trials, the Cochrane Database of Systematic Reviews and CINAHL (Ebsco Platform). Multiple reviewers will screen citations. We will seek studies reporting data collected from individuals with AUD/PAU or providers of treatment for AUD/PAU on service-level factors affecting access to care. We will map barriers to and facilitators of access to AUD/PAU treatment services identified in the relevant studies, stratified by service type and key measures of inequity across service users.Ethics and dissemination This research will enhance awareness of existing evidence regarding barriers to and facilitators of access to services for the treatment of alcohol use disorder and problematic alcohol use. Findings will be disseminated through publications, conference presentations and a stakeholder meeting. As this is a scoping review of published literature, no ethics approval was required.

ObjectiveUniversal health coverage can decrease the magnitude of the individual patient's financial burden of chronic kidney disease (CKD), but the residual financial hardship from the patients' perspective has not been well-studied in low and middle-income countries (LMICs). This study aimed to evaluate the residual financial burden in patients with CKD stage 3 to dialysis in the “PD First Policy” under Universal Coverage Scheme (UCS) in Thailand.MethodsThis multicenter nationwide cross-sectional study in Thailand enrolled 1,224 patients with pre-dialysis CKD, hemodialysis (HD), and peritoneal dialysis (PD) covered by UCS and other health schemes for employees and civil servants. We interviewed patients to estimate the proportion with catastrophic health expenditure (CHE) and medical impoverishment. The risk factors associated with CHE were analyzed by multivariable logistic regression.ResultsUnder UCS, the total out-of-pocket expenditure in HD was over two times higher than PD and nearly six times higher than CKD stages 3–4. HD suffered significantly more CHE and medical impoverishment than PD and pre-dialysis CKD [CHE: 8.5, 9.3, 19.5, 50.0% (p < 0.001) and medical impoverishment: 8.0, 3.1, 11.5, 31.6% (p < 0.001) for CKD Stages 3–4, Stage 5, PD, and HD, respectively]. In the poorest quintile of UCS, medical impoverishment was present in all HD and two-thirds of PD patients. Travel cost was the main driver of CHE in HD. In UCS, the adjusted risk of CHE increased in PD and HD (OR: 3.5 and 16.3, respectively) compared to CKD stage 3.ConclusionsDespite universal coverage, the residual financial burden remained high in patients with kidney failure. CHE was considerably lower in PD than HD, although the rates remained alarmingly high in the poor. The “PD First' program” could serve as a model for other LMICs. However, strategies to minimize financial distress should be further developed, especially for the poor.

Summary: 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.

BackgroundUnderstanding 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.MethodologyA 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 findingsWe 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/significanceThe 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.

Summary: Background: The effect of different music interventions on depression in older adults is varied. We aimed to explore the comparative effect of different music intervention features on depression in older adults. Methods: We searched PubMed, EMBASE, CENTRAL, CINAHL, and ProQuest Dissertations&Theses from inception to October 2021 for randomized controlled trials (RCTs) of music interventions in participants aged ≥60 years. Music interventions were classified based on the TIP (theme, intensity, and provider/platform) framework. The theme was divided into: 1) active music therapy (ACT); 2) receptive music therapy (Recep); and 3) music medicine (MM). The intensity was classified as high (>60 minutes/week), and low (≤60 minutes/week). The provider was classified as a music therapist (MT) or a non-music therapist (NonMT). Summary standardized mean differences (SMD) of level of depression with 95% confidence interval (CI) were estimated using a frequentist framework with a random-effects model. The certainty of evidence was evaluated using the Confidence in Network Meta-Analysis (CINeMA) approach. This study was registered with PROSPERO (CRD42021247165). Findings: Fifteen RCTs involving 1,144 older adults (mean age 67.9-86.6 years) were included. When compared with usual care, the most effective music intervention was active music therapy >60 minutes/week by music therapist (Act/High/MT) (SMD -3.00; 95%CI, -3.64,-2.35), followed by music medicine >60 minutes/week by non-music therapist (MM/High/NonMT) (SMD -2.06; 95%CI, -2.78,-1.35) with moderate and high certainty of evidence, respectively. Depression scores in older adults treated with ACT/High/MT was also significantly lower than all other interventions, except MM/High/NonMT. Low intensity music interventions other than Act/Low/MT had no impact on depression. Interpretation: Although active music therapy >60 minutes/week by music therapist is the most effective intervention to alleviate depression in older adults, music medicine by listening to music of older adult's own preference >60 minutes/week is an alternative approach in settings with limited resources. Funding: None.

IntroductionTobacco 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.MethodsWe 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.ResultsSmokers 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.ConclusionThe 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.

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.

Abstract Background Individuals with advanced colorectal adenomas (ACAs) are at high risk for colorectal cancer (CRC), and it is unclear which chemopreventive agent (CPA) is safe and cost-effective for secondary prevention. We aimed to determine, firstly, the most suitable CPA using network meta-analysis (NMA) and secondly, cost-effectiveness of CPA with or without surveillance colonoscopy (SC). Methods Systematic review and NMA of randomised controlled trials were performed, and the most suitable CPA was chosen based on efficacy and the most favourable risk–benefit profile. The economic benefits of CPA alone, 3 yearly SC alone, and a combination of CPA and SC were determined using the cost-effectiveness analysis (CEA) in the Malaysian health-care perspective. Outcomes were reported as incremental cost-effectiveness ratios (ICERs) in 2018 US Dollars ($) per quality-adjusted life-year (QALY), and life-years (LYs) gained. Results According to NMA, the risk–benefit profile favours the use of aspirin at very-low-dose (ASAVLD, ≤ 100 mg/day) for secondary prevention in individuals with previous ACAs. Celecoxib is the most effective CPA but the cardiovascular adverse events are of concern. According to CEA, the combination strategy (ASAVLD with 3-yearly SC) was cost-saving and dominates its competitors as the best buy option. The probability of being cost-effective for ASAVLD alone, 3-yearly SC alone, and combination strategy were 22%, 26%, and 53%, respectively. Extending the SC interval to five years in combination strategy was more cost-effective when compared to 3-yearly SC alone (ICER of $484/LY gain and $1875/QALY). However, extending to ten years in combination strategy was not cost-effective. Conclusion ASAVLD combined with 3-yearly SC in individuals with ACAs may be a cost-effective strategy for CRC prevention. An extension of SC intervals to five years can be considered in resource-limited countries.

Summary: Background: A number of cost-effectiveness analysis of influenza vaccination have been conducted to estimate value of influenza vaccines in elderly and health workers (HWs). This study aims to summarize cost-effectiveness evidence by pooling the incremental net monetary benefit (INMB) of influenza vaccination. Methods: A systematic review was performed in electronic databases from their inceptions to February 2022. Cost-effectiveness studies reporting quality-adjusted life year (QALY), or life year (LY) of influenza vaccination were included. Stratified meta-analyses by population, perspective, country income-level, and herd-effect were performed to pool INMB across studies. The protocol was registered at PROSPERO (CRD42021246746). Findings: A total of 21 studies were included. Eighteen studies were conducted in elderly, two studies were conducted in HWs, and one study was conducted in both elderly and HWs. According to pre-specified analyses, studies for elderly in high-income economies (countries) (HIEs) and upper-middle income economies (UMIEs) without herd effect could be pooled. For HIEs under a societal perspective, the perspective which identify all relevant costs occurred in the society including direct medical cost, direct non-medical cost and indirect cost, pooled INMB was $217·38 (206·23, 228·53, I2 =28.2%), while that for healthcare provider/payer perspective was $0·20 (-11,908·67, 11,909·07, I2 = 0.0%). For societal perspective in UMIEs, pooled INMB was $28·39 (-190·65, 133·87, I2 = 92.8%). The findings were robust across a series of sensitivity analyses for HIEs. Studies in HWs indicated that influenza vaccination was cost-effective compared to no vaccination or current practice. Interpretation: Influenza vaccination might be cost-effective for HWs and elderly in HIEs under a societal perspective with relatively small variations among included studies, while there remains limited evidence for healthcare provider/payer perspective or other level of incomes. Further evidence is warranted. Funding: This study was funded by a grant of Immunization, Vaccine and Biologicals department of the World Health Organization. The authors would like to acknowledge the contributions of the US CDC which provided financial support to the development and publication of this report. Grant number US CDC, WHO IVR (U50CK000431).

BackgroundA systematic review and network meta-analysis was primarily conducted to compare the effects of synbiotics, probiotics, and prebiotics on aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Moreover, their effects on body mass index (BMI), waist circumference (WC), lipid profile, fasting blood sugar (FBS), and homeostatic model assessment-insulin resistance (HOMA-IR) of patients with non-alcoholic fatty liver disease (NAFLD) were investigated and analyzed as secondary outcomes.MethodsThe randomized controlled trials (RCTs), limited to the English language, were searched through PubMed, the Web of Science, Embase, CLINAHL Plus, and the Cochrane Library from inception to February 2, 2022. The eligible studies were reviewed and their risk-of-bias and heterogeneity were assessed. Both direct and indirect evidence were assembled using a random-effects model. The effects of the intervention were presented as weighted mean differences (WMD) with 95% confidence interval (95% CI).ResultsOf 3,864 identified records, a total of 1,389 patients with NAFLD from 26 RCTs were included in the analyses. Among these, 241 were diagnosed with non-alcoholic steatohepatitis. The quality assessment reported a moderate risk of bias from most studies. Among adult patients with NAFLD, when compared with placebo, synbiotics provided the largest effect on reductions of AST (−12.71 IU/L; 95% CI: −16.95, −8.47), WC (−2.26 cm; 95% CI: −2.98, −1.54), total cholesterol (−22.23 mg/dl; 95% CI: −29.55, −14.90), low-density lipoproteins (−17.72 mg/dl; 95% CI: −25.23, −10.22), and FBS (−6.75 mg/dl; 95% CI: −10.67, −2.84). Probiotics lowered ALT (−14.46 IU/L; 95% CI: −21.33, −7.59) and triglycerides (−20.97 mg/dl; 95% CI: −40.42, −1.53) the most. None had significant impact on BMI, high-density lipoproteins, and HOMA-IR changes.ConclusionSynbiotics and probiotics are likely to be the most potential effective treatments for AST and ALT reduction in adult patients with NAFLD, respectively. Although liver enzymes cannot exactly define the severity of NAFLD, unlike the results from biopsy or imaging tests, they are important indicators that can monitor the status of the disease and provide benefits for clinical management.Systematic Review Registration[https://www.crd.york.ac.uk/prospero/display_reco rd.php?ID], identifier [CRD42020200301].

BackgroundThe use of the internet for research is essential in the practice of evidence-based medicine. The online search habits of medical practitioners in clinical settings, particularly from direct observation, have received little attention. ObjectiveThe goal of the research is to explore online searching for information as an evidence-based practice among medical practitioners. MethodsA cross-sectional study was conducted to evaluate the clinical teams’ use of evidence-based practice when making clinical decisions for their patients' care. Data were collected through online searches from 2015 to 2018. Participants were medical practitioners and medical students in a Malaysian public teaching hospital’s neonatal intensive care unit who performed online searches to find answers to clinical questions that arose during ward rounds. ResultsIn search sessions conducted by the participants, 311 queries were observed from 2015 to 2018. Most participants (34/47, 72%) were house officers and medical students. Most of the searches were conducted by house officers (51/99, 52%) and medical students (32/99, 32%). Most searches (70/99, 71%) were directed rather than self-initiated, and 90% (89/99) were completed individually rather than collaboratively. Participants entered an average of 4 terms in each query; three-quarters of the queries yielded relevant evidence, with two-thirds yielding more than one relevant source of evidence. ConclusionsOur findings suggest that junior doctors and medical students need more training in evidence-based medicine skills such as clinical question formulation and online search techniques for performing independent online searches effectively. However, because the findings were based on intermittent opportunistic observations in a specific clinical setting, they may not be generalizable.

Background: With the increased availability of safe antiretroviral therapy (ART) in recent years, achieving optimal adherence and patient retention is becoming the biggest challenge for people living with HIV (PLWH). Care retention is influenced by several socioeconomic, socio-cultural, and government policies during the COVID-19 pandemic. Therefore, we aim to explore barriers and facilitators to adherence to ART among PLWH in Pakistan in general and COVID-19 pandemic related in particular.Methods: Semi-structured interviews were conducted among 25 PLWH from December 2020 to April 2021 in the local language (Urdu) at the ART centre of Pakistan Institute of Medical Sciences, Islamabad, Pakistan. Interviews were audio-recorded in the local Urdu language, and bilingual expert (English, Urdu) transcribed verbatim, coded for themes and sub-themes, and analyzed using a phenomenological approach for thematic content analysis.Results: Stigma and discrimination, fear of HIV disclosure, economic constraints, forgetfulness, religion (Ramadan, spiritual healing), adverse drug reactions, lack of social support, alternative therapies, and COVID-19-related lock-down and fear of lesser COVID-19 care due to HIV associated stigma were identified as barriers affecting the retention in HIV care. At the same time, positive social support, family responsibilities, use of reminders, the beneficial impact of ART, and initiation of telephone consultations, courier delivery, and long-term delivery of antiretrovirals during COVID-19 were identified as facilitators of HIV retention.Conclusion: Improving adherence and retention is even more challenging due to COVID-19; therefore, it requires the integration of enhanced access to treatment with improved employment and social support. HIV care providers must understand these reported factors comprehensively and treat patients accordingly to ensure the continuum of HIV care. A coordinated approach including different stakeholders is required to facilitate patient retention in HIV care and consequently improve the clinical outcomes of PLWH.

Introduction The number of umbrella reviews (URs) that compiled systematic reviews and meta-analysis (SR-MAs) has increased dramatically over recent years. No formal guidance for assessing the certainty of evidence in URs of meta-analyses exists nowadays. URs of non-interventional studies help establish evidence linking exposure to certain health outcomes in a population. This study aims to identify and describe the methodological approaches for assessing the certainty of the evidence in published URs of non-interventions. Methods We searched from 3 databases including PubMed, Embase, and The Cochrane Library from May 2010 to September 2021. We included URs that included SR-MAs of studies with non-interventions. Two independent reviewers screened and extracted data. We compared URs characteristics stratified by publication year, journal ranking, journal impact factor using Chi-square test. Results Ninety-nine URs have been included. Most were SR-MAs of observational studies evaluating association of non-modifiable risk factors with some outcomes. Only half (56.6%) of the included URs assessed the certainty of the evidence. The most frequently used criteria is credibility assessment (80.4%), followed by GRADE approach (14.3%). URs published in journals with higher journal impact factor assessed certainty of evidence than URs published in lower impact group (77.1 versus 37.2% respectively, p < 0.05). However, criteria for credibility assessment used in four of the seven URs that were published in top ranking journals were slightly varied. Conclusions Half of URs of MAs of non-interventional studies have assessed the certainty of the evidence, in which criteria for credibility assessment was the commonly used method. Guidance and standards are required to ensure the methodological rigor and consistency of certainty of evidence assessment for URs.

[This corrects the article DOI: 10.1371/journal.pone.0230850.].

Backgound: The high incidence of thiopurine-induced myelosuppression in Asians is known to be attributable to genetic variation in thiopurine metabolism. A quantitative synthesis to summarize the genetic association with thiopurine-induced myelosuppression in Asians was therefore conducted.Methods: A Literature search was performed from January 2016 to May 2021 in the following databases: PubMed, Web of Science, and Embase and addition search included the studies from Zhang et al. Two reviewers independently extracted the following data: the author’s name, year of publication, ethnicity, drugs, diseases, genetic polymorphisms, onset, type of myelosuppression and results of Hardy-Weinberg equilibrium. The Newcastle-Ottawa Scale was used to assess the quality of the studies. The pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated to evaluate the associations of NUDT15 and the risk of thiopurine-induced myelosuppression stratified by onset and type of myelosuppressive. Subgroup analysis by NUDT15 genetic polymorphisms was performed.Results: A total of 30 studies was included in this meta-analysis. The overall OR for the relationship between NUDT15 genetic polymorphisms and thiopurine-induced early onset of leukopenia and neutropenia in Asian populations were 11.43 (95% CI 7.11–18.35) and 16.35 (95% CI 10.20–26.22). Among NUDT15 polymorphisms, NUDT15*3 showed a significantly increased risk of early leukopenia (OR 15.31; 95% CI 9.65–24.27) and early neutropenia (OR 15.85; 95% CI 8.80–28.53). A significantly higher thiopurine-induced early neutropenic risk was also found for NUDT15*2 (OR 37.51; 95% CI 1.99–708.69). Whereas, NUDT15*5 and NUDT15*6 variants showed a lower risk of leukopenia.Conclusion: This study suggests that NUDT15*3 and NUDT15*2 are important genetic markers of thiopurine-induced early onset of myelotoxicity in Asians, therefore, early detection of these variants before initiating thiopurine therapy is necessary.

Background: The effects of coffee consumption on hepatic outcomes are controversial. This study investigated the associations between coffee consumption and the incidence of non-alcoholic fatty liver disease (NAFLD) in the general population and the reduction of liver fibrosis among patients with NAFLD.Methods: The study consisted of two parts: an umbrella review and a systematic review and meta-analysis (SRMA). The searches for each part were performed separately using PubMed, EMBASE, Cochrane, Scopus, and CINAHL databases. All articles published up to September 2021 were reviewed. To be eligible, studies for the umbrella review were required to report outcomes that compared the risks of NAFLD in the general population and/or liver fibrosis in patients with NAFLD who did and did not drink coffee. Our SRMA included primary studies reporting the effects of coffee consumption on NAFLD-related outcomes. The outcomes were pooled using a random-effects model and reported in both qualitative and quantitative terms (pooled risk ratio, odds ratio, and weighted mean difference).Results: We identified four published SRMAs during the umbrella review. Most studies showed that individuals in the general population who regularly drank coffee were significantly associated with a lower NAFLD incidence than those who did not. Our SRMA included nine studies on the effects of coffee consumption on NAFLD incidence. Pooled data from 147,875 subjects showed that coffee consumption was not associated with a lower NAFLD incidence in the general population. The between-study heterogeneity was high (I2, 72–85%). Interestingly, among patients with NAFLD (5 studies; n = 3,752), coffee consumption was significantly associated with a reduction in liver fibrosis (odds ratio, 0.67; 95% CI, 0.55 to 0.80; I2, 3%). There were no differences in the coffee consumption of the general population and of those with NAFLD (4 studies; n = 19,482) or by patients with no/mild liver fibrosis and those with significant fibrosis (4 studies; n = 3,331).Conclusions: There are contrasting results on the effects of coffee on NAFLD prevention in the general population. Benefits of coffee consumption on liver fibrosis were seen among patients with NAFLD.Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021226607, identifier CRD42021226607

Background: Pregnancy loss is the most common obstetric complication occurring in almost 30% of conceptions overall and in 12–14% of clinically recognized pregnancies. Pregnancy loss has strong genetic underpinnings, and despite this consensus, our understanding of its genetic causes remains limited. We conducted a systematic review of genetic factors in pregnancy loss to identify strategies to guide future research.Methods: To synthesize data from population-based association studies on genetics of pregnancy loss, we searched PubMed for relevant articles published between 01/01/2000-01/01/2020. We excluded review articles, case studies, studies with limited sample sizes to detect associations (N < 4), descriptive studies, commentaries, and studies with non-genetic etiologies. Studies were classified based on developmental periods in gestation to synthesize data across various developmental epochs.Results: Our search yielded 580 potential titles with 107 (18%) eligible after title/abstract review. Of these, 54 (50%) were selected for systematic review after full-text review. These studies examined either early pregnancy loss (n = 9 [17%]), pregnancy loss >20 weeks' gestation (n = 10 [18%]), recurrent pregnancy loss (n = 32 [59%]), unclassified pregnancy loss (n = 3 [4%]) as their primary outcomes. Multiple genetic pathways that are essential for embryonic/fetal survival as well as human development were identified.Conclusion: Several genetic pathways may play a role in pregnancy loss across developmental periods in gestation. Systematic evaluation of pregnancy loss across developmental epochs, utilizing whole genome sequencing in families may further elucidate causal genetic mechanisms and identify other pathways critical for embryonic/fetal survival.

Over the past few years, many innovative vaccines became available that offer protection for diseases which have never been prevented before. While there are several factors that could have an impact on access, the use of health technology assessment (HTA) undoubtedly is also one of the contributing factors. Objectives: To explore the landscape of vaccine access and the role of HTA in new vaccine adoption in Association of Southeast Asian Nations (ASEAN) countries. Results: A great deal of progress has been made in terms of access to new and innovation vaccine in the region. Variation in access to these vaccines comparing between countries, however, is still observed. The use of HTA in supporting new vaccine adoption is still in an early stage especially in Gavi, the Vaccine Alliance-eligible countries. Conclusions: Improving the use of HTA evidences to support decision making could accelerate the efficient adoption of new vaccine in ASEAN region.

Many interventions have been investigated for the treatment of nonalcoholic steatohepatitis (NASH). This study aims to summarize all investigated options to date and review the use of specific endpoints at different stages of ongoing trials of noncirrhotic NASH treatments. Using a horizon scanning approach, evidence were identified including meta-analyses of randomized controlled trials (RCTs) in PubMed, EMBASE, Cochrane, and AMED (up to February 2020), recently published RCTs in PubMed (2015-April 2020), RCTs presented at conferences (AASL and EASL, 2015–2020), and ongoing RCTs in ClincalTrials.gov (2015-November 2020). We included 6 meta-analyses of RCTs, 30 published RCTs, 11 conference abstracts, and 62 ongoing RCTs. An evidence map was created to demonstrate the treatment effects of 49 therapeutic modalities for NASH. Only six interventions (6/49, 12.24%) met the histological surrogate endpoints for potential conditional FDA approval. Obeticholic acid is the only therapy demonstrating positive benefits in ≥1-point improvement in fibrosis with no worsening of NASH in a phase 3 trial. The other therapies were all phase 2 studies. ≥1-point improvement in fibrosis with no worsening of NASH was shown in patients treated with cenicriviroc. NASH resolution with no worsening of fibrosis was shown in patients treated with liraglutide, semaglutide and resmetirom. Lanifibranor achieved both surrogate histological endpoints. Five ongoing RCTs (5/62, 8.06%) will investigate histological progression to cirrhosis, death, or liver-related clinical outcomes. In conclusion, some therapeutic modalities showed promising benefits, but further studies are warranted to find a definite treatment of NASH which prevents progression to cirrhosis and adverse liver outcomes.

Background and objective: There is an increase in the global prevalence of the human immunodeficiency virus (HIV). While it has been proven that pharmacist interventions improve the health outcomes of people living with HIV/AIDS (PLWHA), the economic impact of these initiatives is uncertain. Consequently, we aim to systematically review and synthesize the evidence surrounding the economic impact of pharmacist care in PLWHA. Methods: PubMed, EMBASE, Scopus, IPA via ProQuest, the Cochrane Library, and the CINAHL Plus databases were systematically searched. Original studies evaluating the economic effect of pharmacist-managed services for PLWHA were included in the review. The quality of the economic studies was assessed using the Consolidated Health Economic Evaluation Reporting Standard (CHEERS) checklist. Results: A search of databases yielded 4206 citations, four of which met the eligibility criteria. Three studies were conducted in a hospital-based outpatient facility, while one study was conducted in a community pharmacy setting. The types of “pharmacist-managed services” included targeted motivational education, pharmaceutical care, health screening for opportunistic infections, and referral to specialists. Two of the four economic evaluation studies had complete economic analyses and were rated as moderate in quality. In comparison with usual care, pharmacist services led to cost savings of (51.29 to 165.74 in 2021 USD$) per person per year, saving 18.5 h per patient per year, and a lower cost of generating 12 years of quality-adjusted life years. In addition, the benefit-to-cost ratio of the pharmacist service was 2.51:1. Conclusions: The pharmacist-managed services demonstrated the benefits of improving overall PLWHA health outcomes in economic viability. However, future real world controlled, high-quality economic studies are required to determine the long-term cost-effectiveness of these services, given the pharmacist's growing role in the health care team managing PLWHA.

Background: Little is known of the efficacy of telemedicine on the clinical outcomes of the high-risk group of non-alcoholic fatty liver disease (NAFLD) patients, such as those with obesity. This study aimed to determine the effects of telemedicine vs. usual care for the management of obese patients with NAFLD.Methods: Literature searches were performed from inception to 1st June 2021 in the following databases: Cochrane CENTRAL, ScienceDirect, PubMed, and Scopus. Prospective trials assessed the effects of telemedicine on obese patients with NAFLD were included. The outcomes of interest were alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride, high-density lipoprotein cholesterol levels, and body mass index, which were reported as weighted mean difference (WMD) with 95% confidence interval (CI).Results: Four studies were examined in the systematic review, one was excluded from the meta-analysis due to an inappropriate group-comparison. In all, 285 obese patients with NAFLD were included in the meta-analysis (70% of those received telemedicine intervention). The mean ages of the patients in the telemedicine and usual-care groups were 51.78 ± 5.91 and 47.30 ± 8.14 years, respectively. Telemedicine significantly decreased ALT levels compared with usual care (WMD = −18.93 U/L [95%CI: −25.97, −11.90]; I2 = 53.8%), and it significantly decreased AST levels (WMD = −10.24 U/L [95%CI: −13.43, −7.05]; I2 = 0.0%). However, telemedicine did not show significant benefits for the remaining outcomes.Conclusion: Compared with usual care, telemedicine significantly reduced the AST and ALT levels of obese patients with NAFLD. Further long-term studies with clinical endpoints are needed to determine the best characteristics of telemedicine and to confirm the benefits.Systematic Review Registration: PROSPERO [CRD42020207451].