Cost-Utility Analysis of TNF-α Inhibitors, B Cell Inhibitors, and JAK Inhibitors Versus csDMARDs for Rheumatoid Arthritis Treatment.

INTRODUCTION: Rheumatoid arthritis (RA) is a progressive and debilitating disease, causing persistent joint pain that limits daily activities requiring long-term treatment. Newer targeted therapies expand RA treatment options, but their high cost necessitates a focus on cost effectiveness. To address this, we aim to conduct a cost-utility analysis of these newer RA pharmacotherapies to support evidence-based policy decision-making. METHODS: We analyzed the cost-utility of sequential treatment with TNF-α, B cell and JAK-inhibitors compared with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) for RA treatment in methotrexate (MTX) nonresponders. We used a Markov model with lifetime horizon and 6-month cycles from an Indian health system perspective. Costs (INR 2022) and quality-adjusted life years (QALYs) were used to determine the incremental cost-effectiveness ratios (ICERs) at a cost-effectiveness threshold of India's gross domestic product (GDP) per capita (2022). We assessed uncertainty using univariate, probabilistic sensitivity, and scenario analyses. RESULTS: Despite additional QALYs, TNF-α, B cell, and JAK inhibitors were not cost-effective for treating moderate-to-severe patients with RA unresponsive to csDMARDs (including MTX) in India, as increased costs outweighed their clinical benefits. ICERs ranged from 10,46,206 to 31,09,207 Indian Rupees in the base case analysis, exceeding three times India's GDP per-capita [approximately USD $13,287 to $39,487 and GBP £10,776 to £32,025]. Sensitivity analyses confirmed the results' robustness. Scenario analysis suggested that a cost reduction of over 75% in drug prices could make most of the interventions cost effective compared with csDMARDs. CONCLUSIONS: TNF-α, B cell, and JAK-inhibitors are not cost-effective compared with csDMARDs for patients with RA who have not responded to MTX in India at the current prices. Cost-effectiveness estimates were highly influenced by drug pricing variations. Therefore, reducing the prices of these interventions could enhance affordability, potentially leading to their inclusion in publicly funded health programs.

Cost-effective analysis of hepatitis A vaccination in Kerala state, India.

Several hepatitis A outbreaks have recently been reported in Kerala state, India. To inform coverage decision of hepatitis A vaccine in Kerala, this study aimed to examine the cost-effectiveness of 1) hepatitis A vaccination among children aged 1 year and individuals aged 15 years, and 2) serological screening of individuals aged 15 years and vaccination of susceptible as compared to no vaccination or vaccination without serological screening. Both live attenuated hepatitis A vaccine and inactivated hepatitis A vaccine were considered in the analysis. A combination of decision tree and Markov models with a cycle length of one year was employed to estimate costs and benefits of different vaccination strategies. Analysis were based on both societal and payer perspectives. The lifetime costs and outcomes were discounted by 3%. Our findings indicated that all strategies were cost-saving for both societal and payer perspectives. Moreover, budget impact analysis revealed that vaccination without screening among individuals aged 15 years could save the government's budget by reducing treatment cost of hepatitis A. Our cost-effectiveness evidence supports the inclusion of hepatitis A vaccination into the vaccination program for children aged 1 year and individuals aged 15 years in Kerala state, India.

Process evaluation of a complex, multilevel, multicomponent scheme for the prevention and control of non-communicable diseases in Tamil Nadu, India: A mixed-methods protocol.

Background: Non-communicable diseases (NCDs) are the leading cause of morbidity and mortality in India, necessitating development of multilevel and multicomponent interventions. Makkalai Thedi Maruthuvam (MTM) is a complex multilevel, multicomponent intervention developed and implemented by the south Indian State of Tamil Nadu. The scheme aims to deliver services for preventing and controlling diabetes, and hypertension at doorstep. This paper describes the protocol for planning and conducting the process evaluation of the MTM scheme. Methods and analysis: The process evaluation uses mixed methods (secondary data analysis, key informant interviews, in-depth interviews, conceptual content analysis of documents, facility-based survey and non-participant observation) to evaluate the implementation of the MTM scheme. The broad evaluation questions addressed the fidelity, contexts, mechanisms of impact and challenges encountered by the scheme using the Consolidated Framework for Implementation Research (CFIR) framework. The specific evaluation questions addressed selected inputs and processes identified as critical to implementation by the stakeholders. The CFIR framework will guide the thematic analysis of the qualitative interviews to explore the adaptations and deviations introduced during implementation in various contexts. The quantitative data on the indicators developed for the specific evaluation questions will be cleaned and descriptively analysed.

Global seroprevalence of scrub typhus: a systematic review and meta-analysis.

Scrub typhus, a neglected disease, is a significant health concern in the Tsutsugamushi triangle of the Asia-Pacific and has raised global concerns due to recent cases occurring outside this region. To estimate the global prevalence of scrub typhus, we conducted a systematic review and meta-analysis. We conducted a systematic search of PubMed, Scopus, and Embase databases for observational studies on scrub typhus. Using a random-effects model, we combined the prevalence estimates with inverse-variance weights while also evaluating heterogeneity and publication bias. Among 3551 reports screened, we identified 181 studies with 1,48,251 samples for inclusion in our synthesis. The overall pooled seroprevalence (95% confidence intervals) of scrub typhus infections was 24.93% (23.27-26.60). Gender-wise pooled prevalence was estimated to be 50.23% (47.05-53.40) for males and 48.84% (45.87-51.80) for females. Eschar prevalence was observed to be 30.34% (22.54-38.15) among the positive cases. One-fourth of all the samples tested positive for scrub typhus and eschar was present in one-third of these total positive cases, encompassing regions beyond the Tsutsugamushi triangle. This estimation underlines the importance of this neglected disease as a public health problem. Strengthening surveillance and implementing disease control measures are needed in the affected regions.

Health-related quality of life in Parkinson's disease: systematic review and meta-analysis of EuroQol (EQ-5D) utility scores.

INTRODUCTION: Evaluating the Health-related quality of life (HRQoL) of individuals with Parkinson's disease (PD) holds significant importance in clinical and research settings. The EQ-5D is a widely recognized tool for comprehensive measurement of HRQoL using utility values. This study aims to systematically review and synthesize EQ-5D utility values from existing literature on patients with PD and their caregivers. METHODS: We conducted a systematic search for studies that provided EQ-5D utility scores for patients with PD, using PubMed-Medline, Scopus, and Embase and selected the studies. The selected studies underwent systematic review, including an assessment of their quality. We performed a meta-analysis using a random-effect model and conducted a meta-regression analysis to investigate sources of heterogeneity among the studies. RESULTS: The search result of 13,417 articles that were reviewed, 130 studies with 33,914 participants were selected for systematic review, and 79 studies were included for meta-analysis. The pooled EQ-5D utility values and visual analog score (VAS) among PD were 62.72% (60.53-64.93, I2 = 99.56%) and 0.60 (0.55-0.65, I2 = 99.81%), respectively. The pooled scores for caregivers' EQ-VAS and EQ-5D utility were 70.10% (63.99-76.20, I2 = 98.25%) and 0.71 (0.61-0.81, I2 = 94.88%), respectively. Disease duration (P < 0.05) showed a negative correlation with EQ-5D utility values on meta-regression. CONCLUSION: The pooled utility values of PD and their caregivers help to understand their HRQoL and aid in conducting health economics research. The negative association between disease duration and utility values highlights the evolving nature of HRQoL challenges, suggesting the need for appropriate long-term disease management.

Pharmacogenomics-assisted schizophrenia management: A hybrid type 2 effectiveness-implementation study protocol to compare the clinical utility, cost-effectiveness, and barriers.

OBJECTIVES: The response to antipsychotic therapy is highly variable. Pharmacogenomic (PGx) factors play a major role in deciding the effectiveness and safety of antipsychotic drugs. A hybrid type 2 effectiveness-implementation research will be conducted to evaluate the clinical utility (safety and efficacy), cost-effectiveness, and facilitators and barriers in implementing PGx-assisted management compared to standard of care in patients with schizophrenia attending a tertiary care hospital in eastern India. METHODS: In part 1, a randomized controlled trial will be conducted. Adult patients with schizophrenia will be randomized (2: 1) to receive PGx-assisted treatment (drug and regimen selection depending on the results of single-nucleotide polymorphisms in genes DRD2, HTR1A, HTR2C, ABCB1, CYP2D6, CYP3A5, and CYP1A2) or the standard of care. Serum drug levels will be measured. The patients will be followed up for 12 weeks. The primary endpoint is the difference in the Udvalg for Kliniske Undersøgelser Side-Effect Rating Scale score between the two arms. In part 2, the cost-effectiveness of PGx-assisted treatment will be evaluated. In part 3, the facilitators and barriers to implementing PGx-assisted treatment for schizophrenia will be explored using a qualitative design. EXPECTED OUTCOME: The study findings will help in understanding whether PGx-assisted management has a clinical utility, whether it is cost-effective, and what are the facilitators and barriers to implementing it in the management of schizophrenia. TRIAL REGISTRATION: The study has been registered with the Clinical Trials Registry-India (CTRI/2023/08/056210).

Evaluating Health Expenditure Trends and Disease Burden in India: A Cost per DALY Approach.

Background: Efficient allocation of healthcare resources requires a comprehensive evaluation of healthcare spending and its impact on disease burden. This study aims to estimate the costs-per disability-adjusted life years (DALY) in India. Data from 2010 to 2019 on DALYs and health expenditure per capita (HEp) for individual states in India were utilised. Design and Methods: We followed the CHEERS statement 2022 to present our study's methodology and outcomes. Pearson's product-moment correlations were used to analyse associations between DALYs and HEp. A panel regression analysis was conducted using a log regression model to estimate changes in DALYs due to health expenditure changes. All costs are reported in Indian rupee (₹) along with its 95% CI, with a conversion factor of 1 US$ = ₹82.4 applied. Results: The costs-per-DALY were estimated for each state and India. DALY was negatively correlated with HEp. The estimated mean cost-per-DALY for India was ₹82,112 (₹55,810 to ₹1,08,413) [$997 ($667 to $1316)]. The mean cost per-DALY varied across states, with value of ₹27,058 (₹22,250 to ₹31,866) [$328 ($270 to $387)] for states in the first quartile based on Human Development Index (HDI) and ₹2,69,175 (₹1,05,946 to ₹4,32,404) [$3267 ($1286 to $5248)] for those in fourth HDI quartile. States such as Gujarat (0.16), Karnataka (0.17) and Maharashtra (0.22) have lower, and Arunachal Pradesh has the highest cost-per-DALY to Gross state domestic product per-capita ratio (2.41), followed by Nagaland (1.45). Conclusion: Higher healthcare investment has a lower disease burden; however, reduction in DALY varies across states. Study findings provide evidence to aid the setting up of differential willingness-to-pay thresholds across Indian states for efficient and equitable healthcare resource allocation.

Clinical effectiveness of ferric carboxymaltose (iv) versus iron sucrose (iv) in treatment of iron deficiency anaemia in pregnancy: A systematic review and meta-analysis.

BACKGROUND OBJECTIVES: Iron deficiency anaemia (IDA) during pregnancy is treated with oral and parenteral iron. The objective of this review was to compare the clinical effectiveness, safety, pregnancy and neonatal outcomes of intravenous (iv) ferric carboxymaltose (FCM) and iv iron sucrose (IS) in treating IDA in pregnancy. METHODS: The Department of Health Research funded this study. PubMed, Cochrane Library, EMBASE and Scopus were searched to include studies published till November 2022. The protocol was registered in PROSPERO (CRD42022306092). Pregnant women (15-49 yr) in second and third trimesters, diagnosed with moderate-to-severe iron deficiency anaemia, treated with either of the drugs were included. The included studies were critically assessed using appropriate tools. We conducted a qualitative synthesis of the studies and meta-analysis for improvement in haematological parameters and incidence of adverse events. RESULTS: A total of 18 studies were included. The risk of bias was low to moderate. A rise in haemoglobin up to four weeks was higher with FCM than IS by 0.57 (0.24, 0.9) g/dl. Intravenous FCM is associated with fewer adverse events than IS [pooled odds ratio: 0.5 (0.32, 0.79)]. The included studies had limited evidence on pregnancy and neonatal outcomes after iv iron treatment. INTERPRETATION CONCLUSIONS: Intravenous FCM is effective and safer than intravenous IS in terms of haematological parameters, in treating IDA in pregnancy. Further research is required on the effects of iv FCM and iv IS on the pregnancy and neonatal outcomes when used for treating IDA in pregnancy.

Cost Effectiveness of Deep Brain Stimulation for Parkinson's Disease: A Systematic Review.

BACKGROUND AND OBJECTIVE: Deep brain stimulation (DBS) is an established treatment for Parkinson's disease (PD) in patients with advanced motor symptoms with an inadequate response to pharmacotherapies. Despite its effectiveness, the cost effectiveness of DBS remains a subject of debate. This systematic review aims to update and synthesize evidence on the cost effectiveness of DBS for PD. METHODS: To identify full economic evaluations that compared the cost effectiveness of DBS with other best medical treatments, a comprehensive search was conducted of the PubMed, Embase, Scopus, and Tufts Cost-Effective Analysis registry databases. The selected papers were systematically reviewed, and the results were summarized. For the quality appraisal, we used the modified economic evaluations bias checklist. The review protocol was a priori registered with PROSPERO, CRD42022345508. RESULTS: Sixteen identified cost-utility analyses that reported 19 comparisons on the use of DBS for PD were systematically reviewed. The studies were primarily conducted in high-income countries and employed Markov models. The costs considered were direct costs: surgical expenses, calibration, pulse generator replacement, and annual drug expenses. The majority of studies used country-specific thresholds. Fourteen comparisons from 12 studies reported on the cost effectiveness of DBS compared to best medical treatments. Eleven comparisons reported DBS as cost effective based on incremental cost-utility ratio results. CONCLUSIONS: The cost effectiveness of DBS for PD varies by time horizon, costs considered, threshold utilized, and stage of PD progression. Standardizing approaches and comparing DBS with other treatments are needed for future research on effective PD management.

Prevalence and risk factors associated with undiagnosed diabetes in India: Insights from NFHS-5 national survey.

Background: Undiagnosed diabetes is a significant public health concern in India, considering the accumulative burden of diabetes and its long-term complications. We have estimated the prevalence and factors associated with undiagnosed diabetes in India. Methods: We used data from the fifth round of the National Family Health Survey (NFHS-5, 2019-21) to estimate undiagnosed diabetes prevalence aged under 50 (15-49) years. A log-binomial model with survey-adjusted Poisson regression was used to estimate the prevalence risk ratio (PR) between undiagnosed diabetes and various factors. Multinomial logistic regression analysis was performed to examine the factors associated with diagnosed diabetes (vs. healthy) and undiagnosed diabetes (vs. healthy). All the analyses were survey-weighted and stratified by gender and reported with 95% confidence intervals. Results: The prevalence of diabetes for individuals aged 15-49 years was found to be 4.90% (4.80 to 5.00%) from the NFHS-5. Among them, the proportion of individuals with undiagnosed diabetes was 24.82% (24.07 to 25.59%), with higher among males (28.82% (26.45 to 31.30%)) than females (24.22% (23.44 to 25.01%)). The overall prevalence of undiagnosed diabetes was 1.22% (1.18 to 1.26%), with a higher prevalence among males (1.60% (1.46 to 1.76%)) than females (1.17% (1.13 to 1.21%)). Individuals who are middle-aged (45-49), have a higher body mass index (BMI), and are in a lower wealth index group, or live in the southern regions of India are at a higher risk of being undiagnosed for diabetes. Conclusion: One in every four having diabetes is undiagnosed. The study highlights the need for public health interventions to improve diabetes screening and access to health care, particularly among middle-aged individuals, and those with higher BMI, as well as addressing lifestyle and dietary factors. The findings also reveal disparities in diabetes burden among population subgroups in India, underscoring the need for targeted efforts.

Burden of mental health disorders and synthesis of community-based mental health intervention measures among adolescents during COVID-19 pandemic in low middle-income countries: A systematic review and meta-analysis.

BACKGROUND: COVID-19 pandemic and the resultant lockdown could have negatively impacted adolescent mental health. The synthesised burden of mental health illness among adolescents during or after the pandemic is unknown in Low Middle-Income Countries (LMICs). The objective was to ascertain the pooled prevalence of mental health disorders among adolescents aged 10 - 19 years and to systematically review & conduct a descriptive synthesis of community-based mental health intervention measures in addressing adolescent mental health disorders during the COVID-19 pandemic in LMICs. METHODS: The literature was searched in Embase, PubMed, and Scopus and selected the relevant studies. The data was extracted from the selected studies, and its quality was assessed using adapted Newcastle-Ottawa Quality Assessment Scales. Meta-analysis was performed using random effects model to pool the prevalence of mental health disorders. Statistical heterogeneity was evaluated through Cochran's Q test & I2 statistic. RESULTS: Thirty-five studies were selected out of 7955 identified studies. Most of the studies (n = 7, each) were from India and Iran. The majority of research works were community-based (n = 18), conducted in 2020 (23 articles), and participant interviews were conducted through online mode (n = 21). Varied instruments were used to measure the burden of mental health in different settings. Pooled prevalence (95% confidence intervals) of anxiety, depression and stress was found to be 43.69 (18.58-68.80)%, 47.02 (31.72-62.32)% and 39.97 (30.53-49.40)%, respectively, with high heterogeneity between the studies. No studies reported community-based mental health interventions. CONCLUSION: There has been a higher prevalence of anxiety, depression, stress, and other mental health illnesses, among adolescents in LMICs during the COVID-19 pandemic. It is important to note that no existing literature directly addresses community-based interventions for these common mental health illnesses. It is imperative to prepare the health system for early identification and management of common mental health illness among the adolescent age group in the event of any future disaster.

Efficacy and safety of bempedoic acid lipid-lowering therapy: a systematic review and meta-analysis of randomized controlled trials.

AIM: This systematic review and meta-analysis was conducted to synthesize the efficacy and safety of bempedoic acid in patients requiring lipid-lowering therapy. METHODS: PubMed, Embase, and Scopus databases were searched for randomized controlled trials from inception till June 2023. The primary outcome was major adverse cardiovascular events (MACE), and secondary outcomes were all-cause mortality, serum lipid profile, and adverse events between bempedoic acid and comparators. ROB2 was used for risk of bias assessment. We pooled mean differences or relative risks (RR) along with 95% confidence intervals (random-effects model). RESULTS: Five-hundred and thirty-one studies were screened and 17 (n = 21,131) were included for review. There was a significant reduction in the risk of MACE [RR, 0.88 (95% CI: 0.77 to 0.99), p = 0.03)] and all-cause mortality [RR, 0.90 (95% CI: 0.82 to 0.98), p = 0.02] following bempedoic acid treatment. Treatment with bempedoic acid led to a significant reduction in the mean serum total cholesterol [- 34.41 mg/dl (95% CI: - 42.43 to - 26.39), p < 0.001], low-density lipoprotein cholesterol (LDL-C) [- 33.91 mg/dl (95% CI: - 39.66 to - 28.17), p < 0.001], as well as high-density lipoprotein cholesterol (HDL-C) [- 2.40 mg/dl (95% CI: - 3.09 to - 1.71), p < 0.001] levels. However, there was a significant increase in the risk of hyperuricemia [RR, 2.05 (95% CI: 1.81 to 2.33), p < 0.001] following bempedoic acid treatment. The number needed to harm was large for all safety outcomes. The GRADE of evidence was moderate for all outcomes. CONCLUSION: Bempedoic acid reduces the risk of MACE and all-cause mortality, lowers serum total cholesterol and LDL-C levels, and has a favorable safety profile. Trial registration ClinicalTrial.gov Identifier: CRD42023412837.

Household catastrophic health expenditures for rheumatoid arthritis: a single centre study from South India.

Rheumatoid arthritis (RA) not only has a physical and emotional toll but also has a substantial economic impact. This study aims to estimate the burden of catastrophic health expenditure (CHE) on households due to RA in Tamil Nadu, India. We conducted cross-sectional descriptive hospital-based single-centre study at a tertiary care private multispecialty hospital in Tamil Nadu, India. The study comprised 320 RA patients who visited the outpatient clinic from April to October 2022. Demographic and baseline descriptive characteristics were reported. Multivariable logistic regression analyses were performed to identify major determinants associated with CHE. We also examined the inequality in household annual income and CHE. Most study participants were females (88.1%) with a mean age (SD) of 55.57 ± 12.29 years. About 93% of RA patients were from urban areas, and 89.4% were literate. Only 8.1% of respondents reported having health insurance. Households experiencing CHE owing to RA were 51.4% (n = 162). The mean (95% CI) annual health expenditure for treating RA is ₹44,700 (₹41,710 to 47,690) with a median (IQR) of ₹39,210 (₹25,500) [$476 ($310)]. The corresponding mean (95% CI) and median (IQR) Out of pocket expenditure among RA patients per household were ₹40,698 (₹38,249 to 43,148) [$494 ($464 to $524)] and ₹36,450 (23,070) [$442 ($280)] respectively. Nearly half of the households with RA patients had a financial catastrophe due to healthcare costs being paid out-of-pocket and limited health insurance coverage. The results underscore the need for comprehensive approaches to strengthening public health policies along with financial risk protection and quality care in India.

Association Between Blood Lead Levels and Thyroid Function: An Updated Systematic Review and Meta-Analysis.

Chronic Lead (Pb) exposure is associated with disrupting certain endocrine levels and is referred to as an endocrine disruptor. Thyroid hormones, involved in regulating numerous physiological functions, are reported with conflicting associations with chronic Pb exposure. This study broadly evaluated the association between long-term lead exposure and thyroid function parameters. In this systematic review, the observational studies documenting the changes in thyroid function parameters between the chronically Pb-exposed and controls were systematically identified from PubMed-Medline, Scopus, and Embase digital databases from the beginning to March 31, 2022. The protocol was previously registered with PROSPERO (ID: CRD42022315520) and executed following PRISMA 2020 guidelines. The random-effects model was used to analyze the mean differences in thyroid function parameters between groups. The classical I2 statistic was applied to assess heterogeneity, while the Newcastle Ottawa Scale was used to assess the risk of various biases. Where data allowed, sub-group, sensitivity, and meta-regression analyses were carried out. The current systematic review included fifteen observational studies. The Pb-exposed have a higher mean blood Pb level [i.e. 28.07 (95% CI 21.43-34.72) µg/dl], significantly higher free T3 [(i.e. 0.48 pg/dl (95% CI 0.05-0.95)] and trend of higher T3. T4, FT4, and TSH levels than controls with high heterogeneity (I2 > 85%). Considering the important role of thyroid hormone in multiple biological functions, the present findings emphasize the requisite for high-quality studies to investigate the association between levels of thyroid function parameters among individuals known for cumulative exposure to Pb. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-023-01113-8.

Cost-effectiveness of tumor necrosis factor-alpha inhibitors: a systematic review and meta-analysis of cost-utility studies.

OBJECTIVE: To systematically review the cost-utility evidence of TNF-a-i treatment for rheumatoid arthritis (RA) and to estimate the pooled incremental net benefit (INBp). METHODS: We selected economic evaluation studies reporting the cost-utility of TNF-a-i compared to other disease-modifying anti-rheumatic drugs (DMARDs) after a systematic search in PubMed, Embase, Scopus, and Tufts Medical Centers' cost-effective analysis registry. The results were reported as pooled INB in purchasing power parity-adjusted US dollars, along with 95% confidence intervals. We used GRADE quality assessment to present summaries of evidence and random-effects meta-analysis to synthesize cost-utility of TNF-a-i. RESULTS: We included 86 studies for systematic review, of which 27 for meta-analysis. TNF-a-i is not cost-effective [$ -4,129(-6,789 to -1,469)] compared to other DMARDs but with high heterogeneity. There was no evidence of publication bias (p = 0.447). On separate analysis, TNF-a-i is not cost-effective [$ -4,805(-7,882 to -1,728)] compared to conventional synthetic DMARDs for RA treatment. GRADE assessment indicated very low confidence in pooled cost-utility results and likely presence of risk of bias on the overall ECOBIAS checklist in studies. CONCLUSION: Based on the available evidence during the study period, TNF-a-i is not a cost-effective option for treating RA compared to other DMARDs. However, high heterogeneity and low confidence in GRADE quality assessment preclude the results from being generalizable.

Global prevalence of asymptomatic dengue infections - a systematic review and meta-analysis.

OBJECTIVES: The burden of asymptomatic dengue infections is understudied. Therefore, we systematically reviewed the literature to estimate the global prevalence of asymptomatic dengue infections. METHODS: We searched cross-sectional studies reporting the prevalence of asymptomatic dengue infections from PubMed, Scopus, and Embase. Prevalence of asymptomatic dengue infections was pooled and reported as proportions with a 95% confidence interval (CI). This systematic review protocol was a priori registered in The International Prospective Register of Systematic Reviews (Reg: No. CRD42020218446). RESULTS: We included 41 studies with 131,953 cases in our analysis. The overall pooled prevalence of asymptomatic dengue infections was 59.26% (95% CI: 43.76-74.75, I2 = 99.93%), with 65.52% (95% CI: 38.73-92.32, I2 = 99.95%) during outbreaks and 30.78% (95% CI: 21.39-40.16, I2 = 98.78%) during non-outbreak periods. The pooled prevalence among the acutely infected individuals was 54.52% (95% CI: 17.73-46.76, I2 = 99.91%), whereas, among primary and secondary asymptomatic dengue infections, it was 65.36% (95% CI: 45.76-84.96, I2 = 98.82) and 48.99% (95% CI: 27.85-70.13, I2 = 99.08%) respectively. CONCLUSION: The majority of dengue cases are asymptomatic and may play a significant role in disease transmission. Public health strategies aimed at dengue outbreak response and mitigation of disease burden should include early detection of asymptomatic cases.

Is COVID-19 severity associated with telomere length? A systematic review and meta-analysis.

Telomere shortening, a marker of cellular aging, has been linked to hospitalization and the severity of COVID-19. In this systematic review and meta-analysis, the mean difference in telomere length between non-severe and severe COVID-19 individuals was pooled to determine the association between short telomeres and COVID-19 severity. Relevant studies were retrieved through searches conducted in PubMed-Medline, Scopus, EMBASE, Medrxiv, Biorxiv, EuroPMC, and SSRN databases up to November 2022. Selected studies were systematically reviewed and assessed for risk of bias using AXIS tool. The standardized mean difference in telomere length between non-severe and severe COVID-19 was pooled using random-effects model. A total of thirteen studies were included in the review, out of which seven (1332 patients with the severe COVID-19 disease and 6321 patients with non-severe COVID-19) were eligible for meta-analysis. The estimated pooled mean difference in Leukocyte telomere length between severe COVID-19 and non-severe COVID-19 was 0.39 (95% CI - 0.02 to 0.81, I2 = 93.5%) with substantial heterogeneity. Our findings do not provide clear evidence for association of shorter telomere length and severe COVID-19 disease. More extensive studies measuring absolute telomere length with age and gender adjustments are needed to draw definitive conclusions on the potential causal association between telomere shortening and COVID-19 severity.

Cost-utility of Ranolazine for Chronic Stable Angina Pectoris: Systematic Review and Meta-analysis.

PURPOSE: Ranolazine is used to treat stable angina pectoris, the most common symptom of ischemic heart disease. Appropriate management of chronic stable angina pectoris is essential from both a clinical and an economic view point. METHODS: This systematic review and meta-analysis adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We included cost-utility analyses, which compared ranolazine with other standard treatments for treating stable angina pectoris. The search was conducted in PubMed, EMBASE, and Scopus databases. A random-effects model based on the DerSimonian and Laird method was used to pool the incremental net benefit reported in purchasing power parity adjusted US dollars. The modified economic evaluation checklist was used to assess the risk of bias. FINDINGS: The pooled results from 7 selected studies with a time horizon of 1 year show that add-on ranolazine was significantly cost-effective compared with standard treatment, with a pooled incremental net benefit of US$1335 (95% CI, 500 to 2169) but with substantial heterogeneity (I2 = 79.46%). On subgroup analysis, ranolazine was cost-effective from the payers' perspective (US$1975; 95% CI, 1042 to 2908; I2 = 69.23) but not from a societal perspective (US$297; 95% CI, -241 to 715; I2 = 0%)]. There was limited evidence from lower economies. IMPLICATIONS: Pooled evidence suggests that add-on ranolazine therapy is cost-effective for chronic stable angina pectoris up to a 1-year time horizon. There is a lacuna of evidence from low- and middle-income countries and on long-term cost-effectiveness. The current evidence synthesis may provide a macroeconomic point of view for policy makers regarding the direction of ranolazine's cost-effectiveness for evidence-informed policy-making. PROSPERO identifier: CRD42022332454.

Health-related quality of life and associated factors among COVID-19 individuals managed with indian traditional medicine: A cross-sectional study from south India.

Introduction: Coronavirus disease-2019 (COVID-19) had a multidimensional impact on human life. It affects the health-related quality of life (HRQoL) which is a perceived measure of physical and mental health. We estimated the EuroQol utility value for COVID-19 and the associated factors for those managed at Siddha COVID care centres in Tamil Nadu. Methods: A cross-sectional study was conducted by a telephonic interview of 2000 randomly selected COVID-19 adults tested positive during June 2020 to Jan 2021. We collected sociodemographic, clinical and EQ-5D-5L profile. Mean EQ-5D-5L summary utility values and EQ-VAS scores were estimated. Multivariate regression was used to examine the factors associated with EQ-5D-5L. Study protocol was approved by the Institutional ethics committee of Government Siddha Medical College, Chennai (GSMC-CH-3401/ME-2/050/2021). The committee waived the written informed consent considering the pandemic situation of emerging infectious diseases. Results: We interviewed 1047 participants. Of the total 68% were males with the median age (IQR) of 38 (29-51) years. The mean EQ-5D-5L utility score and EQ-VAS scores are 0.98 ± 0.05 and 92.14 ± 0.39 respectively. COVID-19 asymptomatic group reported a mean utility score of 0.99 ± 0.03 which is relatively more than the symptomatic group (0.97 ± 0.06),. EQ-VAS score was also reported high among the asymptomatic (95.45 ± 5.95) than the symptomatic (91.40 ± 8.69COVID-19. Conclusion: The severity of illness and the comorbidity are significantly associated with a low HRQoL of COVID-19 patients.

Cost Effectiveness of Rituximab Therapy for Rheumatoid Arthritis: A Systematic Review and Meta-Analysis of Cost-Utility Studies.

BACKGROUND AND OBJECTIVES: Depletion of B cells is shown to be clinically effective for rheumatoid arthritis (RA) treatment. Although B-cell depletion therapy with rituximab is indicated for RA patients who have failed to other disease-modifying anti-rheumatic drugs (DMARDs), primary cost-effectiveness evidence is inconsistent. We aimed to provide synthesised cost-effectiveness evidence of rituximab in the treatment of RA compared to other DMARDs, since the published cost-effectiveness evidence is mixed. METHODS: We identified economic evaluation studies reporting cost-utility of rituximab compared to other DMARDs by searching PubMed, Embase, Scopus, and Tufts Cost-Effective Analysis registry. Using random-effects meta-analysis, we pooled incremental net benefit (INB) in (purchasing power parity) adjusted US$ with 95% confidence intervals. We used the modified economic evaluations bias checklist and Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) instrument for quality appraisal. The study protocol was pre-registered with PROSPERO, CRD 42021222541. RESULTS: Of the selected 18 studies, the majority were from high-income countries (n = 14) followed by upper middle-income countries (n = 3) and lower middle-income countries (n = 1), with minimal risk of bias. Rituximab is significantly cost effective with a pooled INB (95% CI) of $8767 (720 to 16,814). On subgroup analysis, rituximab is significantly cost effective from a health system perspective [$12,832 (3392 to 22,272)], for studies using 3.5% discount rate [$15,468 (5973 to 24,963)] and a for a time horizon of less than 5 years [$8496 (1547 to 15,445)]. In a separate analysis, rituximab as third-line therapy (for conventional synthetic DMARDs followed by any other biologic DMARD failed patients) was not cost effective compared to DMARDs [$5314 (-2278 to 12,905)]. Further, the GRADE assessment indicated very-low confidence in the pooled results. CONCLUSION: Rituximab is cost effective compared to other DMARDs but not if used as third-line therapy after failure of biologics. There is a need to generate context-specific evidence for the lower income settings.