Karma Healthcare

ABSTRACT BACKGROUND: Wiskott-Aldrich Syndrome (WAS) is a rare, X-linked, life-threatening inborn error of immunity and platelet disorder caused by WAS protein (WASP)-encoding gene mutations. Etuvetidigene autotemcel (etu-cel) is an autologous gene therapy (GT) consisting of hematopoietic stem progenitor cell (HSPCs) transduced ex vivo with a lentiviral vector encoding human WAS cDNA. METHODS Etu-cel was intravenously infused after rituximab and reduced-intensity conditioning. Data from WAS patients treated in two prospective open-label clinical trials (phase I/II n=8; phase III n=10) and one expanded access program (EAP) (n=9) were integrated to evaluate efficacy and safety of etu-cel. Primary efficacy endpoints were overall survival, rate of severe infections from 6 to 18 months after GT and rate of moderate/severe bleeding episodes in the first 12 months post-treatment compared with 1 year prior to GT. Secondary efficacy endpoints included engraftment of gene-corrected cells, WASP expression, T-cell function, platelet count, autoimmunity and eczema over time. Safety endpoints included adverse events (AEs), immune response to transgene, development of replication-competent lentivirus (RCL) and abnormal clonal proliferation (ACP). RESULTS Median follow-up was 5.7 years (range: 0.4-13.3). Median age at treatment was 2.6 years (range: 1.0-35.1). Overall survival was 96%; one EAP subject died early post-GT due to deterioration of a pre-existing neurological condition. The rate of severe infections per person-year of observation (PYO) decreased from 2.00 (95% CI: 1.50-2.61) pre-GT to 0.15 (95% CI: 0.04-0.39) in the 6-18 months period post-GT. The rate of moderate and severe bleeding events per PYO decreased from 2.00 (95% CI: 1.50-2.61) to 0.80 (95% CI: 0.49-1.22) in the 12 months after GT. After GT, multilineage engraftment of gene-corrected cells was sustained over time. WASP expression in platelets and lymphocytes increased. Platelet count, T-cell functionality, eczema and autoimmunity improved. The most common adverse event ≥ grade 3 was device related infection. Etu-cel was well-tolerated with no treatment-related adverse events and no evidence of insertional oncogenesis. CONCLUSIONS With up to 13 years follow-up, etu-cel demonstrates a favorable benefit-risk profile, leading to sustained long-term clinical benefit. (Funded by GlaxoSmithKline [GSK], Orchard Therapeutics, Fondazione Telethon; ClinicalTrials.gov numbers: NCT01515462 , NCT03837483 )

Introduction:Cancer is becoming a leading cause of death and disability across the globe and India too has a high burden of disease with poor outcomes. The national cancer screening program has been rolled out since 2010 but has not yielded the desired results so far. The objective of the present review is to perform an analysis of the strengths and weaknesses of the cancer screening component of the National Program - Non Communicable Disease (NP-NCD) program based on a scoping review of policies, organization, and status of implementation of the program at the primary and secondary levels and also on observations from field experience of the program managers and other health professionals from selected states in India. Methods: A A mixed methodology was used to document the status of the implementation of the ongoing cancer screening program in India. The methodology included a literature review, observation of the frontline health professionals and an in-depth discussion with those in managerial capacity at the health facilities or the screening program. Results:Cancer screening is a complex public health initiative requiring a highly organized framework for effective implementation. Although India has implemented a comprehensive Non-Communicable Disease (NCD) screening program since 2010, the results have been minimal. The latest National Family Health Survey (NHFS 2019-21) reported that among the female population aged 30 to 49 years, only 1.9% and 0.9% were ever screened for cervical cancer and breast cancer respectively. The proportion of 30-49 year-old males reported to be ever screened for oral cancer was only 1.2%. Tamil Nadu and Kerala showed significantly better screening participation compared to other states in the country. Conclusion:Cancer screening is a complex public health initiative requiring a highly organized framework for effective implementation. The Ayushman Bharat comprehensive primary healthcare service package and plan to deliver cancer screening through the Health and Wellness centers (AB-HWCs) is a good opportunity to revamp the program.

This case study discusses the ethical challenges encountered by a primary care team in managing a 17-year-old girl with Type 1 diabetes in a socio-economically deprived tribal area. The case highlights critical issues such as justice in access to essential medicines, ethical dilemmas arising from complex family dynamics, and systemic failures within the public health system. By examining these challenges, this case study underscores the importance of addressing broader social determinants of health to ensure just and effective healthcare delivery in rural and tribal settings.