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$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 CRD4202122254

Dementia and Diabetes Mellitus: Association with Apolipoprotein E4 Polymorphism from a Hospital in Southern India

Objective. To evaluate the association of Apolipoprotein E4 (ApoE4) in Alzheimer's dementia (AD) with comorbid diabetes mellitus (DM). Methods. The study included subjects with Alzheimer's dementia (AD) (n = 209), individuals with non-Alzheimer's dementia (nAD) (n = 122), individuals with parental history of AD (f/hAD) (n = 70), and control individuals who had normal cognitive functions and no parental history of dementia (NC) (n = 193). Dementia was diagnosed using International Classification of Diseases-10 revision (ICD-10) criteria. DM was assessed on the basis of self-report and/or use of antidiabetic medications. ApoE genotyping was done using sequence-specific primer polymerase chain reaction. Results. ApoE4 allele frequencies were highest among AD with comorbid DM (0.35) followed by AD without DM (0.25), nAD with DM (0.13), nAD without comorbid DM (0.12), and NC (0.08). Frequency of ApoE4 in persons with f/hAD was 0.13. The association of AD with co-morbid DM in ApoE4 carriers was more in comparison to NC with DM (OR = 5.68, P = 0.04). Conclusion. There is a significant association between AD with co-morbid DM and ApoE4 genotype

The incremental net benefit of lipid-lowering therapy with PCSK9 inhibitors: A Systematic Review and Meta-analysis of cost-utility studies

Introduction: Proprotein convertase subtilisin/kexin 9 inhibitors (PCSK9i) are monoclonal antibodies that lower lipid levels by inhibiting PCSK9. Although several cardiovascular outcome trials reported beneficial clinical effectiveness of PCSK9i, the evidence on cost-effectiveness is mixed. We systematically reviewed the evidence on cost-effectiveness and synthesized incremental net benefit (INB) to quantify the pooled cost-effectiveness of PCSK9i lipid-lowering therapy. Methods: We systematically searched for full economic evaluation studies reporting outcomes of PCSK9 inhibitors compared with any other lipid-lowering pharmacotherapies. We searched PubMed, Embase, Scopus, and Tufts Registry for eligible studies up-to September 2020, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. We pooled the INB with a 95% confidence interval using a random-effects model. We assessed the Heterogeneity using the Cochrane-Q test and I2 statistic. We used the modified economic evaluations bias (ECOBIAS) checklist to evaluate the quality of the selected studies. Results: A total of 20 studies were eligible, mainly from high-income countries (HIC). The pooled INB of PCSK9i versus other lipid-lowering pharmacotherapies were estimated from n=21 comparisons; with high heterogeneity (I2=98.04). The INBp (95% CI) was US$-46,665 (-196,203; 102,874), PCSK9i was found to be not cost-effective when compared with other standard therapies; however, this finding was not statistically significant. On subgroup analysis PCSK9i was significantly not cost-effective [US$ -25,686 (-26,085;-25,287), I2=0] compared to other lipid-lowering pharmacotherapies among HICs, with payers perspective [US$-25,686 (-26,086;-25,287), I2=0] and with higher discount rates of 5$ -25,686 (-26,086;-25,287), I2=0]. The sensitivity analysis revealed the subgroup findings are not robust. Conclusion: PCSK9is’ are not cost-effective compared to other lipid-lowering pharmacotherapies in HICs. Further, current pieces of evidence are predominantly from HICs with largely lacking evidence from other economies. Prospero registration: ID CRD4202020604

DHA Manuscript

Purpose: To investigate the role of DHA supplementation in preventing Age Related Cognitive Decline (ARCD) in cognitive domains by conducting systematic review and meta-analysis. Methods: Relevant clinical trials were systematically searched at Medline-Pubmed, Scopus, Cochrane, ProQuest and Embase databases since inception to June 2018. The PRISMA guidelines were adhered for data abstraction, quality assessment and validity of included randomized control trails. Study details such as participant characteristics, DHA supplementation and cognitive function outcome measures i.e. memory, attention, working memory and executive function scores, were extracted and performed meta-analysis according to Cochrane guidelines. Additional meta-regression and subgroup analysis was performed to detect confounding variables and sensitivity of results respectively. Results: Ten studies including 2327 elderly individuals were part of the final results. Study exhibited minimal or no pooled incremental effects on memory (0.22, 95%CI=-0.17 to 0.61, I2=94.36%, p<0.001), attention (0.1, 95%CI=-0.04 to 0.25, I2=32.25%, p=0.18), working memory (0.01, 95%CI=-0.10 to 0.12, I2=0%, p=0.89) and executive function (0.03, 95%CI=-0.05 to 0.11, I2=78.48%, p<0.001) among DHA supplemented group. While results from standard mean difference between groups on memory (0.08, 95%CI=-0.12 to 0.28, I2=76.82%, p<0.001), attention (0.04, 95%CI=-0.09 to 0.23, I2=42.63%, p=0.11), working memory (-0.08, 95%CI=-0.26 to 0.10, I2=37.57%, p=0.17) and executive function (0.17, 95%CI=-0.01 to 0.36, I2=78.48%, p<0.001). Results remained unaffected in multiple sensitivity and sub-group analyses. Conclusions: Current evidences don’t support the role of DHA supplementation, in preventing / retarding ARCD of memory, executive function, attention and working memory. Protocol registered at PROSPERO (ID: PROSPERO 2018 CRD42018099401)

Glucagon-like peptide 1 agonists for treatment of patients with type 2 diabetes who fail metformin monotherapy: systematic review and meta-analysis of economic evaluation studies

Objectives To conduct a systematic review and meta-analysis and to pool the incremental net benefits (INBs) of glucagon-like peptide 1 (GLP1) compared with other therapies in type 2 diabetes mellitus (T2DM) after metformin monotherapy failure.Research design and methods The study design is a systematic review and meta-analysis. We searched MEDLINE (via PubMed), Scopus and Tufts Registry for eligible cost–utility studies up to June 2018, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. We conducted a systematic review and pooled the INBs of GLP1s compared with other therapies in T2DM after metformin monotherapy failure. Various monetary units were converted to purchasing power parity, adjusted to 2017 US$. The INBs were calculated and then pooled across studies, stratified by level of country income; a random-effects model was used if heterogeneity was present, and a fixed-effects model if it was absent. Heterogeneity was assessed using Q test and I2 statistic.Results A total of 56 studies were eligible, mainly from high-income countries (HICs). The pooled INBs of GLP1s compared with dipeptidyl peptidase-4 inhibitor (DPP4i) (n=10), sulfonylureas (n=6), thiazolidinedione (TZD) (n=3), and insulin (n=23) from HICs were US$4012.21 (95% CI US$−571.43 to US$8595.84, I2=0%), US$3857.34 (95$−7293.93 to US$15 008.61, I2=45.9$37 577.74 (95% CI US$−649.02 to US$75 804.50, I2=92.4%) and US$14 062.42 (95$8168.69 to US$19 956.15, I2=86.4$4555.09 (95% CI US$3992.60 to US$5117.59, I2=0) and US$728.46 (95$−1436.14 to US$2893.07, I2=0), respectively.Conclusion GLP1 agonists are a cost-effective choice compared with insulins, but not compared with DPP4i, sulfonylureas and TZDs.PROSPERO registration number CRD42018105193

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

Abstract 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

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