Exploring factors contributing to patient decision-making in the care journey to elective hernia care in Kenya

by Helen W. Li, Jesse Kiprono Too, Sarah Nyanchama Nyariki, Charles Nathan Nessle, Sara Malone, Rachel Matsumoto, Teddy Ashibende Aurah, Jeffrey A. Blatnik, JoAnna Hunter-Squires, Ivan Seno Saruni

Background

Capacity for elective general surgical care is an important reflection of a health system’s ability to meet a population’s surgical needs and is currently known to be inadequate in many low- and middle-income countries. Patient agency is a key, understudied factor which shapes how and when patients ultimately decide to engage with formal care. Understanding factors which influence patient care seeking activity can have important implications for how current and future health systems may be utilized. This study aims to explore how patients approach the navigation and triage of their elective hernia condition within the Kenyan surgical care system.

Methods

We conducted a qualitative study of 38 convenience-sampled patients diagnosed with an elective hernia condition at a tertiary referral hospital in Kenya between November 2023 and March 2024. We utilized Braun and Clarke’s six-step model of thematic analysis to generate key themes across the phases of care seeking, reaching and receiving as modeled in the Three Delays Framework.

Results

We identified three main cross-cutting themes including (1) the flow of power from patients to providers, and vice versa, take the form of consent or knowledge, respectively; (2) trust is a limited currency required for patients to engage with formal care; and (3) internal and external contextual factors remain the foundation for patient-provider care activities. We incorporated these themes together in a framework which illustrates the cyclical nature by which each factor feeds back on the others, ultimately affecting patient care.

Conclusions

Fluctuating flows of patient power and trust interacts with existing infrastructural context to influence the ability of a health system to generate care. Recognizing the interaction of these key factors may have important bearing on the successful implementation of any larger systemic efforts or policies to improve access to elective surgical care.

Analytical validation of a homologous recombination deficiency signature (HRDsig) in pan-tumor tissue samples

by Wenshu Li, Jeffrey A. Leibowitz, Shuoguo Wang, Louisa Walker, Chang Xu, Kuei-Ting Chen, Alexa B. Schrock, Jason Hughes, Nimesh Patel, Julia A. Elvin, Lauren L. Ritterhouse, Ethan Sokol, Garrett Frampton, Lucas Dennis, Bahar Yilmazel, Brennan Decker

Homologous recombination repair (HRR) is a cellular pathway for high-fidelity double strand DNA break repair that uses the sister chromatid as a guide to ensure chromosomal integrity and cell viability. Deficiency in the HRR pathway (HRD) can sensitize tumors to poly (ADP-ribose) polymerase inhibitors (PARPi) and platinum-based chemotherapy, offering an avenue to identify patients who may benefit from targeted therapies. HRD signature (HRDsig) is a pan-solid-tumor biomarker on the FoundationOne®CDx (F1CDx®) assay that employs a DNA scar-based approach to calculate a score based on copy number features (e.g., segment size, oscillation patterns, and breakpoints per chromosome arm) and does not rely on HRR gene alterations, enabling detection of genomic and epigenetic mechanisms of HRD. After finalizing the HRDsig algorithm, analytical validation was conducted in a CAP-accredited, CLIA-certified laboratory on 278 solid tumor and normal tissue specimens. HRDsig results were compared with an independent HRD biomarker, defined by the presence of a reversion mutation restoring HRR gene function. In this evaluation, 100 HRD-positive and 126 HRD-negative samples showed a positive percent agreement of 90.00% and a negative percent agreement of 94.44%. The limit of detection (LoD) was estimated at 23.04% tumor purity, with the limit of blank (LoB) confirmed as zero in 60 normal tissue replicates. Reproducibility testing on 11 positive and 11 negative samples across multiple labs, reagent lots, and sequencers yielded agreement in 99.49% of positive and 99.73% of negative replicates. HRDsig status remained consistent in the presence of interfering substances, demonstrating 100% concordance in spiked samples. These validation results underscore the high analytical concordance, low false-positive rate, and overall robustness of HRDsig for reliable assessment of homologous recombination deficiency.