Cost-Effectiveness of Annual Prostate MRI and Potential MRI-Guided Biopsy After Prostate-Specific Antigen Test Results.

Importance: Magnetic resonance imaging (MRI) and potential MRI-guided biopsy enable enhanced identification of clinically significant prostate cancer. Despite proven efficacy, MRI and potential MRI-guided biopsy remain costly, and there is limited evidence regarding the cost-effectiveness of this approach in general and for different prostate-specific antigen (PSA) strata. Objective: To examine the cost-effectiveness of integrating annual MRI and potential MRI-guided biopsy as part of clinical decision-making for men after being screened for prostate cancer compared with standard biopsy. Design, Setting, and Participants: Using a decision analytic Markov cohort model, an economic evaluation was conducted projecting outcomes over 10 years for a hypothetical cohort of 65-year-old men in the US with 4 different PSA strata (<2.5 ng/mL, 2.5-4.0 ng/mL, 4.1-10.0 ng/mL, >10 ng/mL) identified by screening through Monte Carlo microsimulation with 10 000 trials. Model inputs for probabilities, costs in 2020 US dollars, and quality-adjusted life-years (QALYs) were from the literature and expert consultation. The model was specifically designed to reflect the US health care system, adopting a federal payer perspective (ie, Medicare). Exposures: Magnetic resonance imaging with potential MRI-guided biopsy and standard biopsy. Main Outcomes and Measures: Incremental cost-effectiveness ratios (ICERs) using a willingness-to-pay threshold of $100 000 per QALY was estimated. One-way and probabilistic sensitivity analyses were performed. Results: For the 3 PSA strata of 2.5 ng/mL or greater, the MRI and potential MRI-guided biopsy strategy was cost-effective compared with standard biopsy (PSA 2.5-4.0 ng/mL: base-case ICER, $21 131/QALY; PSA 4.1-10.0 ng/mL: base-case ICER, $12 336/QALY; PSA >10.0 ng/mL: base-case ICER, $6000/QALY). Results varied depending on the diagnostic accuracy of MRI and potential MRI-guided biopsy. Results of probabilistic sensitivity analyses showed that the MRI and potential MRI-guided biopsy strategy was cost-effective at the willingness-to-pay threshold of $100 000 per QALY in a range between 76% and 81% of simulations for each of the 3 PSA strata of 2.5 ng/mL or more. Conclusions and Relevance: This economic evaluation of a hypothetical cohort suggests that an annual MRI and potential MRI-guided biopsy was a cost-effective option from a US federal payer perspective compared with standard biopsy for newly eligible male Medicare beneficiaries with a serum PSA level of 2.5 ng/mL or more.

Design of novel JAK3 Inhibitors towards Rheumatoid Arthritis using molecular docking analysis.

Multiple cytokines play a pivotal role in the pathogenesis of Rheumatoid Arthritis by inducing intracellular signaling and it is known that the members of the Janus kinase (JAK) family are essential for such signal transduction. Janus kinase 3 is a tyrosine kinase that belongs to the Janus family of kinases. Drugs targeting JAK3 in the treatment of Rheumatoid arthritis is relevant. Therefore, it is of interest to design suitable inhibitors for JAK3 dimer using molecular docking with Molegro Virtual Docker. The compound possessing the highest affinity score is subjected to virtual screening to retrieve inhibitors. The compound SCHEMBL19100243 (PubChem CID- 76749591) displays a high affinity with the target protein. The affinity scores of this compound are more than known drugs. ADMET analysis and BOILED Egg plot provide insights into this compound as a potent inhibitor of JAK3.

Structure-based Virtual Screening for the Identification of High-affinity Small Molecule Towards STAT3 for the Clinical Treatment of Osteosarcoma.

BACKGROUND: According to DCEG investigation, the compared results of the osteosarcoma incidences in different continents, reported it to be the most diagnosed in adolescents and adults above 60 yrs. old. Less than 15% of patients get cured with surgery alone but the addition of chemotherapy to the treatment increases the survival rate of patient by 58%-76%. Surgical resection and aggressive chemotherapy protocols are effective to an extent but have failed to improve the 5-year overall survival rate. Indubitably, new drugs and new therapeutic targets are required to improve the outcome as well as to diminish the long-term toxicities associated with the current benchmark of treatment. STAT3 appears to be an important mediator of chemoresistance in osteosarcoma. RESULTS: Experimental evidence clearly demonstrate the disruption of STAT3 signaling which inhibits the survival and proliferation of osteosarcoma and decreases the growth of disease. This prevailing study approach is by molecular docking, virtual screening to elucidate inhibitor with superior affinity against STAT3 to have a cautious pharma profile. To rectify the best-established drug with high affinity, Mol dock algorithm is executed. The compound Sorafenib (Pub CID 216239) having high-affinity scores is subjected to another similarity search to retrieve the drugs with similar properties. The virtual screened compound with PubChem CID-44815014 as per BOILED-Egg plot reveals its high affinity. CONCLUSION: Comparative study and ADMET study both showed the compounds to have equivalent properties, whereas interestingly the virtual screened compound having PubChem CID-44815014 is seen to have the lowest rerank score. These drugs are identified to have high potential to act as STAT3 inhibitors and probably can be considered for further studies in wet lab analysis.