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.

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.

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.

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-effectiveness of cholecystectomy compared to conservative management in people presenting with uncomplicated symptomatic gallstones or cholecystitis in India.

OBJECTIVES: Gallstone diseases impose a significant economic burden on the health care system; thus, determining cost-effective management for gallstones is essential. We aim to estimate the cost-effectiveness of cholecystectomy compared with conservative management in individuals with uncomplicated symptomatic gallstones or cholecystitis in India. METHODS: A decision-analytic Markov model was used to compare the costs and QALY of early laparoscopic cholecystectomy (ELC), delayed laparoscopic cholecystectomy (DLC), and conservative management (CM) in patients with symptomatic uncomplicated gallstone/cholecystitis from an Indian health system perspective. Incremental cost-effectiveness ratio (ICER) was calculated. One-way and probabilistic sensitivity analyses were performed to test parameter uncertainties. RESULTS: ELC and DLC, compared to CM, incurred an incremental cost of -₹10,948 ($146) and ₹1,054 ($14) for the 0.032 QALYs gained. The ICER was -₹3,42,758 ($4577) for ELC vs. CM, and ₹33,183 ($443) for DLC vs. CM, suggesting ELC and DLC are cost-effective. ELC saved ₹12,001 ($160) for 0.0002 QALYs gained compared to DLC, resulting in an ICER of -₹6,43,89,441 ($8,59,733). The results were robust to changes in the input parameters in sensitivity analyses. CONCLUSION: ELC is dominant compared to both DLC and CM, and DLC is more cost-effective than CM. Thus, ELC may be preferable to other gallstone disease managements.

Cost-effectiveness of janus kinase inhibitors for rheumatoid arthritis: A systematic review and meta-analysis of cost-utility studies.

Introduction: Janus kinase inhibitors (JAK-i), a class of targeted synthetic disease-modifying antirheumatic drugs (tDMARDs), are suggested as second or third-line therapies in rheumatoid arthritis (RA). Synthesized cost-effective evidence would aid in informed decision-making given the similar clinical effectiveness of JAKi, but incongruent cost-effectiveness reports. Methods: Literature search was conducted in PubMed, Embase, Scopus, and Tufts Medical Centers' cost-effective analysis registry. We pooled the incremental net benefit (INB) with 95% confidence interval (CI) using random-effects model and the heterogeneity was assessed using Cochrane-Q test and I2 statistic. Modified economic evaluation bias checklist was used to assess the quality of selected studies. Publication bias was assessed using a funnel plot and Egger's test. The Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) assessment was performed to assess the certainty of outcomes presented. Results: We included seventeen relevant studies for systematic review, of which fifteen were eligible for meta-analysis. The meta-analysis results showed that JAK-i is cost-effective compared to csDMARDS/bDMARDs with a pooled INB (INBp) of $19,886 (95% CI, 1,635 to 38,137) but with considerable heterogeneity (I2 = 99.14). As a second-line treatment for csDMARD failed RA, JAK-i is cost-effective than csDMARD/bDMARD with a pooled INB of $23,144 (74.1-46,214) and high heterogeneity (I2 = 99.67). But on a separate analysis JAK-i as second-line treatment is not cost-effective than TNF-a-i (INBp = $25,813, -5,714 to 57,340). However, leave-one-out analysis found that omitting a single outlier makes JAK-i cost-effective. Further, JAK-i is not cost-effective as a third-line treatment for csDMARD-TNF-a-I failed RA, compared to csDMARDs/bDMARDs with INBp $26,157 (-7,284 to 59,598). Conclusion: Meta-analysis suggests that JAK-i is cost-effective when used after csDMARD failure but not cost-effective when used after csDMARD-TNF-a-i failure with low certainty of evidence. Clinical Trial Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021222541, identifier CRD42021222541.

Health-related quality of life among patients with gallstone disease: a systematic review and meta-analysis of EQ-5D utility scores.

PURPOSE: Gallstone disease or cholelithiasis is a chronic illness that usually presents with pain in the abdomen, vomiting and indigestion leading to impaired quality of life. EQ-5D utility score is a validated measure of health-related quality of life (HRQoL). We systematically reviewed the literature and synthesised EQ-5D utility scores among patients with gallstone disease and its improvement on treatment. METHODS: We have systematically searched observational studies reporting EQ-5D utility scores of gallstone disease in PubMed, Scopus, and Embase databases, from inception until February 2021. We selected the studies adhering to the PRISMA guidelines. The selected studies were reviewed, and the EQ-5D utility values of pre and post cholecystectomy were pooled using the random-effects model. RESULT: From identified 4,817 records of database search, eleven studies predominantly from western countries with 2,189 participants were included for systematic review and meta-analysis. The pooled EQ-5D and visual analogue scores were 0.87 (0.82 to 0.91, I2 = 93.73%) and 83.30 (60.59 to 106.12, I2 = 99.30%) respectively with high heterogeneity. The pooled EQ-5D and EQ-5D visual analogue scores post cholecystectomy treatment were 0.93 (0.91 to 0.95, I2 = 90.17%) and 91.7 (85.99 to 96.35, I2 = 97.93%) respectively. The mean difference between the baseline and post intervention were 0.05 (0.01 to 0.10, I2 = 93.50%) and 10.58 (-8.63 to 29.79, I2 = 98.32%) for EQ-5D and visual analogue scores respectively with high heterogeneity between the studies. CONCLUSION: The pooled mean difference indicates improvement in HRQoL after cholecystectomy but with high heterogeneity. Further high-quality studies from Asian countries are required for globally representative quantification and precise estimates of HRQoL among gallstone diseases. PROSPERO REGISTRATION ID: CRD42021234467.

Association Between Janus Kinase Inhibitors Therapy and Mental Health Outcome in Rheumatoid Arthritis: A Systematic Review and Meta-analysis.

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic debilitating illness, usually associated with mental health ailments. Literature reports contradictory observations about the association between recent RA pharmacotherapies and mental health. We systematically reviewed RA randomized control trials to synthesize the association between Janus kinases (JAK) inhibitors therapy and mental health. METHODS: We systematically searched clinical trials of JAK inhibitor intervention reporting mental health outcomes using short form-36 (SF-36) in PubMed, Embase, and Scopus databases from inception to February 2021. We have selected the studies and extracted the data, adhering to Preferred Reporting Items of Systematic reviews and Meta-Analysis (PRISMA) guidelines. We have pooled the mean change of SF-36 mental component score (MCS) between JAK inhibitors and comparator therapy with a 95% confidence interval. RESULTS: Of the 2915 searched studies for systematic review, 19 studies involving 14,323 individuals were included for the meta-analysis. The pooled mean reduction in SF-36 MCS scores (after minus before) with JAK inhibitors was 4.95 (4.41-5.48). The pooled mean difference of incremental mean change in SF-36 MCS score between JAK monotherapy and comparator was 1.53 (0.88-2.18). The improvement in SF-36 MCS scores with JAK inhibitor therapy is greater than the minimum clinically important difference (MCID) value of 2.5. However, on separate analysis with comparator drugs like methotrexate and standard treatment, the MCS scores did not exceeded the MCID value and were also not statistically significant. CONCLUSIONS: JAK inhibitors results in clinically meaningful improvement in the mental health scores of the RA patients. PROSPERO REGISTRATION ID: 2021 CRD42021234466.

Systematic review and meta-analysis of gallstone disease treatment outcomes in early cholecystectomy versus conservative management/delayed cholecystectomy.

BACKGROUND: The effectiveness of early cholecystectomy for gallstone diseases treatment is uncertain compared with conservative management/delayed cholecystectomy. AIMS: To synthesise treatment outcomes of early cholecystectomy versus conservative management/delayed cholecystectomy in terms of its safety and effectiveness. DESIGN: We systematically searched randomised control trials investigating the effectiveness of early cholecystectomy compared with conservative management/delayed cholecystectomy. We pooled the risk ratios with a 95% CI, also estimated adjusted number needed to treat to harm. RESULTS: Of the 40 included studies for systematic review, 39 studies with 4483 patients are included in meta-analysis. Among the risk ratios of gallstone complications, pain (0.38, 0.20 to 0.74), cholangitis (0.52, 0.28 to 0.97) and total biliary complications (0.33, 0.20 to 0.55) are significantly lower with early cholecystectomy. Adjusted number needed to treat to harm of early cholecystectomy compared with conservative management/delayed cholecystectomy are, for pain 12.5 (8.3 to 33.3), biliary pancreatitis >1000 (50-100), common bile duct stones 100 (33.3 to 100), cholangitis (100 (25-100), total biliary complications 5.9 (4.3 to 9.1) and mortality >1000 (100 to100 000). CONCLUSIONS: Early cholecystectomy may result in fewer biliary complications and a reduction in reported abdominal pain than conservative management. PROSPERO REGISTRATION NUMBER: 2020 CRD42020192612.

Cost-effectiveness of surgical mask, N-95 respirator, hand-hygiene and surgical mask with hand hygiene in the prevention of COVID-19: Cost effectiveness analysis from Indian context.

INTRODUCTION: In the absence of specific treatment, preventive strategies are of paramount importance in management of coronavirus disease 2019(COVID-19) pandemic. We estimated cost-effectiveness of non-pharmacological interventions such as hand-hygiene, surgical-mask N-95 respirators and surgical mask in general population. METHODS: We performed a decision tree and markov-model based economic evaluation. We estimated total costs and outcomes from public payer's perspective, based on information available through systematic literature search on relative intervention effect during early pandemic phase. We estimated outcomes as number COVID-19 prevented and Quality Adjusted life year (QALY) over one-year time-horizon with one-day cycle-length. Incremental cost effectiveness ratios (ICER) was calculated multiple sensitivity analyses were applied to assess parameter uncertainty. RESULTS: Use of surgical mask with hand hygiene, fit tested N-95 respirator, surgical-mask, non-fit tested N-95 and hand-hygiene interventions prevented additional 1139, 1124, 1121, 1043 and 975 COVID-19 cases per-million as compared to using none. Additional costs incurred (in billion) were ₹29.78 ($0.40), ₹148.09 ($1.99), ₹72.51 ($0.98), ₹26.84 ($0.36) and ₹2.48 ($0.03) as well as additional QALYs gained were 357.4, 353.01, 327.95, 351.52 and 307.04 for surgical mask with hand hygiene, fit-tested N-95, non-fit-tested N-95, surgical mask and hand-hygiene respectively. ICERs with surgical with hand hygiene, hand-hygiene alone, surgical-mask alone, N-95 respirator fit and non-fit test were 83.32($1.12), 8.07($0.11), 76.36($1.03), 419.51($5.65) and 221.10 ($2.98) million ₹ ($)/QALY respectively. Results were robust on uncertainty analysis. DISCUSSION: Among the non-pharmacological interventions to be considered for preventing spread of COVID-19, hand hygiene was cost-effective and avoidance of use of surgical masks and respirators by the general public could save resources.

Health-related quality of life in rheumatoid arthritis: Systematic review and meta-analysis of EuroQoL (EQ-5D) utility scores from Asia.

INTRODUCTION: Region-specific health-related quality of life (HRQoL) scores or utility values are representative and pivotal for economic evaluations as they are influenced by the value judgment of the local population. This study systematically reviewed and pooled EuroQoL-5 Dimension (EQ-5D) utility scores of rheumatoid arthritis (RA) across primary studies from Asia. METHODS: Studies reporting EQ-5D utility scores among adult RA patients from Asian countries were systematically searched in PubMed-Medline, Scopus and Embase since inception through February 2020. Selected studies were systematically reviewed and study quality assessment was performed. Meta-analysis was performed using a random-effect model with subgroup and meta-regression analysis to explore heterogeneity. RESULTS: Among 1391 searched articles, 37 studies with 31 983 participants were systematically reviewed and meta-analysis was conducted among 31 studies. The pooled EQ-5D scores and EQ-5D visual analog score were 0.66 (95% CI 0.63-0.69, I2  = 99.65%) and 61.21 (50.73-71.69, I2  = 99.56%) respectively with high heterogeneity. For RA patients with no, low, moderate and high disease activity based on Disease Activity Score (DAS)-28, the pooled EQ-5D scores were 0.78 (0.65-0.90), 0.73 (0.65-0.80), 0.53 (0.32- 0.74), and 0.47 (0.32-0.62), respectively. On meta-regression, age of patients (P < .05) was positively associated and use of glucocorticoids (P < .05) was inversely associated with utility values. CONCLUSION: Lower EQ-5D scores were associated with severe disease activity, increasing age and female gender among RA patients. The study provides pooled EQ-5D scores for RA patients that are useful inputs for cost-utility studies in Asia.

Blood lead levels and male reproductive hormones: A systematic review and meta-analysis.

Present study aimed to systematically review and synthesise quantitative evidence on association between occupational Lead (Pb) exposure and male reproductive hormones (MRH) and sperm quality from the existing literature. Observational studies investigating the effects of Pb exposure on MRH, sperm-count and sperm motility are systematically searched in PubMed, Scopus and EMBASE databases since inception to May 2019. The PRISMA guidelines are adhered during the entire study procedure and details such as participant characteristics, occupational Pb exposure, MRH, sperm-count and sperm motility from individual articles are extracted to the perform meta-analysis. Sub-group analysis and sensitivity analysis are additionally explored. Further, meta-regression is executed to investigate the influence of participant's age, duration of workplace Pb exposure on the individual outcome parameters. We observed that otherwise normal (fertile) male participants from all studies were within the age range of 25-45 years. Male employees occupationally exposed to Pb exhibited significantly higher blood Pb, lower sperm-count, poor sperm motility and higher serum prolactin levels as compared to the Pb unexposed males. The testosterone, follicle stimulating hormone and luteinising hormone levels of the occupationally Pb exposed participants are comparable to that of unexposed comparators. Studies included for synthesising quantitative evidence had unacceptable levels of heterogeneity. Explorative subgroup or meta-regression analysis had no additional results to the study. Lastly, included studies were driven by publication bias (positive results) and low powered (small sample size) studies. Thus, Pb exposure at workplaces is detrimental to male reproductive function, with lower sperm-count and higher prolactin levels. However, to enumerate the precise quantity of Pb exposure detrimental on male reproductive functions, high quality longitudinal studies with large cohorts are needed.

The effects of changes in glutathione levels through exogenous agents on intracellular cysteine content and protein adduct formation in chronic alcohol-treated VL17A cells.

Alcohol-mediated liver injury is associated with changes in the level of the major cellular antioxidant glutathione (GSH). It is interesting to investigate if the changes in intracellular GSH level through exogenous agents affect the intracellular cysteine content and the protein adduct formation indicative of oxidative insult in chronic alcohol treated liver cells. In VL-17A cells treated with 2 mM N-acetyl cysteine (NAC) or 0.1 mM ursodeoxycholic acid (UDCA) plus 100 mM ethanol, an increase in cysteine concentration which was accompanied by decreases in hydroxynonenal (HNE) and glutathionylated protein adducts were observed. Pretreatment of 100 mM ethanol treated VL-17A cells with 0.4 mM buthionine sulfoximine (BSO) or 1 mM diethyl maleate (DEM) had opposite effects. Thus, altered GSH level through exogenous agents may either potentiate or ameliorate chronic alcohol-mediated protein adduct formation and change the cysteine level in chronic alcohol treated VL-17A cells. The gene expression of non-treated and ethanol-treated hepatocytes in 2 microarray datasets was also compared to locate differentially expressed genes involved in cysteine metabolism. The study demonstrates that increased protein adducts formation and changes in cysteine concentration occur under chronic alcohol condition in liver cells which may increase alcohol-mediated oxidative injury.