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Lynch syndrome (LS) is an inherited cancer predisposition disorder associated with an elevated risk of developing various solid cancers, but mostly colorectal cancer (CRC). Despite having the same germline pathogenic variant (PV) in one of the mis-match repair genes or the EPCAM gene, Lynch syndrome variant heterozygotes (LSVH) exhibit a remarkable phenotypic variability in the risk of developing cancer. The role of human leukocyte antigen (HLA) in modifying cancer development risk prompted our hypothesis into whether HLA variations act as potential genetic modifiers influencing the age at cancer diagnosis in LSVH. To investigate this, we studied a unique cohort of 426 LSVH carrying the same germline PV in the hMLH1 gene (MLH1:c.1528C > T) in South Africa. We intuitively selected 100 LSVH with the greatest diversity in age at cancer diagnosis (N = 80) and the oldest cancer unaffected LSVH (N = 20) for a high-throughput HLA genotyping of 11 HLA class I and class II loci using the shotgun next-generation sequencing (NGS) technique on the Illumina MiSeq platform. Statistical analyses employed Kaplan–Meier survival analyses with log-rank tests, and Cox proportional hazards using binned HLA data to minimize type I error. Significant associations were observed between young age at cancer diagnosis and HLA-DPB1*04:02 (mean age: 37 y (25–50); hazard ratio (HR) = 3.37; corrected p-value (q) = 0.043) as well as HLA-DPB1 binned alleles (including HLA-DPB1*09:01, HLA-DPB1*10:01, HLA-DPB1*106:01, HLA-DPB1*18:01, HLA-DPB1*20:01, HLA-DPB1*26:01, HLA-DPB1*28:01, HLA-DPB1*296:01, and HLA-DPB1*55:01) (mean age: 37 y (17–63); HR = 2.30, q = 0.045). The involvement of HLA-DPB1 alleles in the age at cancer diagnosis may highlight the potential role of HLA class II in the immune response against cancer development in LSVH. When validated in a larger cohort, these high-risk HLA-DPB1 alleles could be factored into cancer risk prediction models for personalized cancer screening in LSVH. [ABSTRACT FROM AUTHOR]

Objective: The irrational use of antibiotics is a leading contributor to antibiotic resistance. Antibiotic stewardship (AS) interventions predominantly focus on prescribers. This study investigated the influence and participation of inpatients in infection‐related care, including antibiotic decision‐making, within and across two tertiary hospitals in South Africa (Cape Town) and India (Kerala). Methods: Through ethnographic enquiry of clinical practice in surgical pathways, including direct nonparticipant observation of clinical practices, healthcare worker (HCW), patient and carer interactions in surgical ward rounds and face‐to‐face interviews with participants (HCWs and patients), we sought to capture the implicit and explicit influence that patients and carers have in infection‐related care. Field notes and interview transcripts were thematically coded, aided by NVivo 12® Pro software. Results: Whilst observational data revealed the nuanced roles that patients/carers play in antibiotic decision‐making, HCWs did not recognize these roles. Patients and carers, though invested in patient care, are not routinely involved, nor are they aware of the opportunities for engagement in infection‐related decision‐making. Patients associated clinical improvement with antibiotic use and did not consider hospitalization to be associated with infection acquisition or transmission, highlighting a lack of understanding of the threat of infection and antibiotic resistance. Patients' economic and cultural positionalities may influence their infection‐related behaviours. In the study site in India, cultural norms mean that carers play widespread but unrecognized roles in inpatient care, participating in infection prevention activities. Conclusion: For patients to have a valuable role in AS and make informed decisions regarding their infection‐related care, a mutual understanding of their role in this process among HCWs and patients is crucial. The observed differences between the two study sites indicate the critical need for understanding and addressing the contextual drivers that impact effective patient‐centred healthcare delivery. Patient or Public Contribution: Ethnographic observations and interviews conducted in this study involved patients as participants. Patients were recruited for interviews after obtaining signed informed consent forms. Patients' identities were completely anonymized when presenting the study findings. [ABSTRACT FROM AUTHOR]

To investigate the drivers for infection management and antimicrobial stewardship (AMS) across high-infection-risk surgical pathways. A qualitative study—ethnographic observation of clinical practices, patient case studies, and face-to-face interviews with healthcare professionals (HCPs) and patients—was conducted across cardiovascular and thoracic and gastrointestinal surgical pathways in South Africa (SA) and India. Aided by Nvivo 11 software, data were coded and analysed until saturation was reached. The multiple modes of enquiry enabled cross-validation and triangulation of findings. Between July 2018 and August 2019, data were gathered from 190 hours of non-participant observations (138 India, 72 SA), interviews with HCPs (44 India, 61 SA), patients (six India, eight SA), and case studies (four India, two SA). Across the surgical pathway, multiple barriers impede effective infection management and AMS. The existing implicit roles of HCPs (including nurses and senior surgeons) are overlooked as interventions target junior doctors, bypassing the opportunity for integrating infection-related care across the surgical team. Critically, the ownership of decisions remains with the operating surgeons, and entrenched hierarchies restrict the inclusion of other HCPs in decision-making. The structural foundations to enable staff to change their behaviours and participate in infection-related surgical care are lacking. Identifying the implicit existing HCP roles in infection management is critical and will facilitate the development of effective and transparent processes across the surgical team for optimized care. Applying a framework approach that includes nurse leadership, empowering pharmacists and engaging surgical leads, is essential for integrated AMS and infection-related care. [ABSTRACT FROM AUTHOR]