Cost‑Effectiveness of TrueNat as Compared to GeneXpert as a Diagnostic Tool for Diagnosis of Pediatric Tuberculosis/MDR Tuberculosis under the National Tuberculosis Elimination Program of India

Background: According to a study on global burden of tuberculosis (TB), India witnessed 60,000 pediatric deaths in the year 2015. In India, most of the children do not get diagnosed with tuberculosis for various reasons. Aims and Objectives: This study will evaluate the cost‑effectiveness of TrueNat and GeneXpert diagnostic strategies used for tuberculosis detection in children, thus aiding policymakers for taking evidence‑based decisions. Materials and Methods: For this cost‑effectiveness study, a systematic review was done to extract the evidence for estimates of effectiveness of current TB diagnostic tools. Evidence pertinent to cost per test including all direct, indirect costs and health benefits in terms of quality‑adjusted life years were researched and documented. Full economic evaluations available in the literature were also explored. Results: The results of the study showed that TrueNat is more cost‑effective when compared to GeneXpert in the diagnosis of pediatric tuberculosis cases leading to more life years gained and deaths averted. 13,260 additional cases can be detected with TrueNat with an incremental cost of $14.36 per additional case detected. The incremental cost‑effectiveness ratio per life year gained was found to be 20.01.Conclusion: TrueNat proved to be beneficial and cost‑effective as compared to GeneXpert MTB being used in case of children. We recommend the use of TrueNat diagnostic test in India as it is in congruence with Indian health‑care settings

Study of inside-out technique of trans-obturator tape for treatment of stress urinary incontinence in women with utero-vaginal prolapse

Background: Assessment of the success rates and complications of inside-out technique of Trans-Vaginal Tape (Obturator) (TVT-O) for treatment of stress urinary incontinence (SUI) in women with utero-vaginal prolapse. Materials and Methods: A total of 30 consenting subjects with SUI and utero-vaginal prolapse were subjected to TVT-O surgery. These subjects were closely monitored for complications and success rate of surgery up to 1 year of surgery. Results: Urinary tract infection (16.67%) was the most common early post-operative complication. Groin pain (23%) was the most common late post-operative complication while denovo urgency developed in 3 (11.54%) subjects. Majority (88.46%) of subjects had total improvement at 3month follow-up while 100% subjects had total improvement at 12 month follow-up with a "definitely improved quality-of-life." Conclusion: The TVT-O (inside-out) appears to have performed favorably as a safe and effective surgery for SUI associated with utero-vaginal prolapse

Cost-Effectiveness of currently available diagnostic tools for diagnosis of pediatric tuberculosis under national tuberculosis elimination program

In India, children do not get diagnosed with tuberculosis (TB) for reasons such as lack of screening modality at the health-care settings, inadequate sputum sample, and low detection rate. This study aims to assess various modalities for diagnosis of pediatric TB and their cost-effectiveness. Cost-effectiveness was found for various diagnostic modalities for TB diagnosis in children of India below 15 years of age. TrueNat MTB was the intervention being compared to GeneXpert MTB and sputum microscopy. Evidence pertinent to effectiveness and cost per test, and health benefits in terms of disability adjusted life years were researched and documented. Modeling a cohort of children through a decision tree and assimilating costs and disability-adjusted life years (DALYs) at each step gave results in the form of cost-effectiveness. Interventions were compared by calculating the cost-effectiveness ratio. The results revealed that TrueNat is more cost effective (Rs. 9450/DALY averted) compared to GeneXpert MTB/RIF (Rs. 9750/DALY averted). The incremental cost effectiveness ratio of TrueNat with respect to GeneXpert was found to be Rs. 5925 per DALY averted. Diagnosis through TrueNat point of care (POC) will avert 962 more DALYs compared to GeneXpert. As is evident from the results, TrueNat does alleviate disability caused by TB in children as more DALYs are averted. At an additional cost of Rs. 5925 to avert one DALY, which is below the gross domestic product (GDP) per capita for India (for 2021, it was $2277), TrueNat can have significant health benefits

Health technology assessment of video otoscopy for the diagnosis of otitis media in children in comparison to conventional otoscopy in primary healthcare settings in India

Objective: This Health Technology Assessment (HTA) was undertaken to assess the clinical-effectiveness, cost-effectiveness, and operational feasibility of using otoscopes in primary healthcare settings in India, for diagnosing otitis media in children. Methods: We undertook a three-step process sequentially determining (i) clinical effectiveness of video as well as conventional otoscopy (compared to otic microscope as the reference standard); (ii)cost-effectiveness analysis of the video otoscope; and (iii)operational feasibility and health equity considerations. The systematic review for clinical effectiveness involved literature search across five databases, screening and inclusion of relevant studies, and data synthesis. Cost-effectiveness analysis was performed using data from published literature, specialist interviews, and cost assumptions if neither was available. The Progress Plus tool was used to explore health equity and operational feasibility was taken into account. Results: The systematic review on clinical effectiveness include three relevant studies from a total of 1361 identified. The pooled sensitivity and specificity of video otoscope were 0.70 (95%CI 0.60, 0.84) and 0.92 (CI95% 0.89, 0.95) to be 0.88 (95% CI, 0.84 to 0.91). The cost-effectiveness analysis identified the incremental cost-effectiveness ratio (compared to conventional otoscope) as INR 1008.4 per QALY, with an overall gain of 413 QALYs per year. This was well below the willingness-to-pay threshold for India. There was potential of enhancing health equity and no insurmountable operational barriers, to the use of video otoscope in primary healthcare settings. Conclusion: This HTA concluded that video otoscope is clinically effective, cost-effective, and operationally feasible in Indian primary health settings, for diagnosing otitis media in children

Three-year survival, correlates and salvage therapies in patients receiving first-line pembrolizumab for advanced Merkel cell carcinoma

Background Merkel cell carcinoma (MCC) is an aggressive skin cancer associated with poor survival. Programmed cell death-1 (PD-1) pathway inhibitors have shown high rates of durable tumor regression compared with chemotherapy for MCC. The current study was undertaken to assess baseline and on-treatment factors associated with MCC regression and 3-year survival, and to explore the effects of salvage therapies in patients experiencing initial non-response or tumor progression after response or stable disease following first-line pembrolizumab therapy on Cancer Immunotherapy Trials Network-09/KEYNOTE-017.Methods In this multicenter phase II trial, 50 patients with advanced unresectable MCC received pembrolizumab 2 mg/kg every 3 weeks for ≤2 years. Patients were followed for a median of 31.8 months.Results Overall response rate to pembrolizumab was 58% (complete response 30%+partial response 28%; 95% CI 43.2 to 71.8). Among 29 responders, the median response duration was not reached (NR) at 3 years (range 1.0+ to 51.8+ months). Median progression-free survival (PFS) was 16.8 months (95% CI 4.6 to 43.4) and the 3-year PFS was 39.1%. Median OS was NR; the 3-year OS was 59.4% for all patients and 89.5% for responders. Baseline Eastern Cooperative Oncology Group performance status of 0, greater per cent tumor reduction, completion of 2 years of treatment and low neutrophil-to-lymphocyte ratio were associated with response and longer survival. Among patients with initial disease progression or those who developed progression after response or stable disease, some had extended survival with subsequent treatments including chemotherapies and immunotherapies.Conclusions This study represents the longest available follow-up from any first-line anti-programmed death-(ligand) 1 (anti-PD-(L)1) therapy in MCC, confirming durable PFS and OS in a proportion of patients. After initial tumor progression or relapse following response, some patients receiving salvage therapies survived. Improving the management of anti-PD-(L)1-refractory MCC remains a challenge and a high priority.Trial registration number NCT02267603

Evaluation of Ultra Clean Fuels from Natural Gas

ConocoPhillips, in conjunction with Nexant Inc., Penn State University, and Cummins Engine Co., joined with the U.S. Department of Energy (DOE) National Energy Technology Laboratory (NETL) in a cooperative agreement to perform a comprehensive study of new ultra clean fuels (UCFs) produced from remote sources of natural gas. The project study consists of three primary tasks: an environmental Life Cycle Assessment (LCA), a Market Study, and a series of Engine Tests to evaluate the potential markets for Ultra Clean Fuels. The overall objective of DOE's Ultra Clean Transportation Fuels Initiative is to develop and deploy technologies that will produce ultra-clean burning transportation fuels for the 21st century from both petroleum and non-petroleum resources. These fuels will: (1) Enable vehicles to comply with future emission requirements; (2) Be compatible with the existing liquid fuels infrastructure; (3) Enable vehicle efficiencies to be significantly increased, with concomitantly reduced CO{sub 2} emissions; (4) Be obtainable from a fossil resource, alone or in combination with other hydrocarbon materials such as refinery wastes, municipal wastes, biomass, and coal; and (5) Be competitive with current petroleum fuels. The objectives of the ConocoPhillips Ultra Clean Fuels Project are to perform a comprehensive life cycle analysis and to conduct a market study on ultra clean fuels of commercial interest produced from natural gas, and, in addition, perform engine tests for Fisher-Tropsch diesel and methanol in neat, blended or special formulations to obtain data on emissions. This resulting data will be used to optimize fuel compositions and engine operation in order to minimize the release of atmospheric pollutants resulting from the fuel combustion. Development and testing of both direct and indirect methanol fuel cells was to be conducted and the optimum properties of a suitable fuel-grade methanol was to be defined. The results of the study are also applicable to coal-derived FT liquid fuels. After different gas clean up processes steps, the coal-derived syngas will produce FT liquid fuels that have similar properties to natural gas derived FT liquids

Neoadjuvant Nivolumab for Patients With Resectable Merkel Cell Carcinoma in the CheckMate 358 Trial

PURPOSE Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer commonly driven by the Merkel cell polyomavirus (MCPyV). The programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) immunosuppressive pathway is often upregulated in MCC, and advanced metastatic MCC frequently responds to PD-1 blockade. We report what we believe to be the first trial of anti-PD-1 in the neoadjuvant setting for resectable MCC. METHODS In the phase I/II CheckMate 358 study of virus-associated cancer types, patients with resectable MCC received nivolumab 240 mg intravenously on days 1 and 15. Surgery was planned on day 29. Tumor regression was assessed radiographically and microscopically. Tumor MCPyV status, PD-L1 expression, and tumor mutational burden (TMB) were assessed in pretreatment tumor biopsies. RESULTS Thirty-nine patients with American Joint Committee on Cancer stage IIA-IV resectable MCC received $1 nivolumab dose. Three patients (7.7$ 30%. Responses were observed regardless of tumor MCPyV, PD-L1, or TMB status. At a median follow-up of 20.3 months, median recurrence-free survival (RFS) and overall survival were not reached. RFS significantly correlated with pCR and radiographic response at the time of surgery. No patient with a pCR had tumor relapse during observation. CONCLUSION Nivolumab administered approximately 4 weeks before surgery in MCC was generally tolerable and induced pCRs and radiographic tumor regressions in approximately one half of treated patients. These early markers of response significantly predicted improved RFS. Additional investigation of these promising findings is warranted