'Walking together': How relationships shape physicians' clinical reasoning.

INTRODUCTION: The clinical reasoning literature has increasingly considered context as an important influence on physicians' thinking. Physicians' relationships with patients, and their ongoing efforts to maintain these relationships, are important influences on how clinical reasoning is contextualised. The authors sought to understand how physicians' relationships with patients shaped their clinical reasoning. METHODS: Drawing from constructivist grounded theory, the authors conducted semi-structured interviews with primary care physicians. Participants were asked to reflect on recent challenging clinical experiences, and probing questions were used to explore how participants attended to or leveraged relationships in conjunction with their clinical reasoning. Using constant comparison, three investigators coded transcripts, organising the data into codes and conceptual categories. The research team drew from these codes and categories to develop theory about the phenomenon of interest. RESULTS: The authors interviewed 15 primary care physicians with a range of experience in practice and identified patient agency as a central influence on participants' clinical reasoning. Participants drew from and managed relationships with patients while attending to patients' agency in three ways. First, participants described how contextualised illness constructions enabled them to individualise their approaches to diagnosis and management. Second, participants managed tensions between enacting their typical approaches to clinical problems and adapting their approaches to foster ongoing relationships with patients. Finally, participants attended to relationships with patients' caregivers, seeing these individuals' contributions as important influences on how their clinical reasoning could be enacted within patients' unique social contexts. CONCLUSION: Clinical reasoning is influenced in important ways by physicians' efforts to both draw from, and maintain, their relationships with patients and patients' caregivers. Such efforts create tensions between their professional standards of care and their orientations toward patient-centredness. These influences of relationships on physicians' clinical reasoning have important implications for training and clinical practice.

How to Keep Training-After Residency Training.

Lifelong learning in medicine is an important skill and ethical obligation, but many residents do not feel prepared to be effective self-directed learners when training ends. The learning sciences offer evidence to guide self-directed learning, but these insights have not been integrated into a practical and actionable plan for residents to improve their clinical knowledge and reasoning. We encourage residents to establish a self-directed learning plan, just as an athlete employs a training plan in the pursuit of excellence. We highlight four evidence-based learning principles (spaced practice, mixed practice, retrieval practice, and feedback) and four training strategies comprising a weekly training plan: case tracking, simulated cases, quizzing, and new evidence integration. We provide tips for residents to implement and refine their approach and discuss how residency programs can foster these routines and habits. By optimizing their scarce self-directed learning time with a training plan, residents may enhance patient care and their career satisfaction through their pursuit of clinical mastery.

Characterization of TP53 mutations in Pap test DNA of women with and without serous ovarian carcinoma.

OBJECTIVE: Pap tests hold promise as a molecular diagnostic for serous ovarian cancer, but previous studies reported limited sensitivity. Furthermore, the presence of somatic mutations in normal tissue is increasingly recognized as a challenge to the specificity of mutation-based cancer diagnostics. We applied an ultra-deep sequencing method with the goal of improving sensitivity and characterizing the landscape of low-frequency somatic TP53 mutations in Pap tests. METHODS: We used CRISPR-DS to deeply sequence (mean Duplex depth ~3000×) the TP53 gene in 30 Pap tests from 21 women without cancer and 9 women with serous ovarian carcinoma with known TP53 driver mutations. Mutations were annotated and compared to those in the TP53 cancer database. RESULTS: The tumor-derived mutation was identified in 3 of 8 Pap tests from women with ovarian cancer and intact tubes. In addition, 221 low-frequency (≲0.001) exonic TP53 mutations were identified in Pap tests from women with ovarian cancer (94 mutations) and without ovarian cancer (127 mutations). Many of these mutations resembled TP53 mutations found in cancer: they impaired protein activity, were predicted to be pathogenic, and clustered in exons 5 to 8 and hotspot codons. Cancer-like mutations were identified in all women but at higher frequency in women with ovarian cancer. CONCLUSIONS: Pap tests have low sensitivity for ovarian cancer detection and carry abundant low-frequency TP53 mutations. These mutations are more frequently pathogenic in women with ovarian cancer. Determining whether low-frequency TP53 mutations in normal gynecologic tissues are associated with an increased cancer risk warrants further study.

TP53 somatic evolution in cervical liquid-based cytology and blood from individuals with and without ovarian cancer and BRCA1 or BRCA2 germline mutations.

Somatic TP53 mutations are prevalent in normal tissue but little is known about their association with cancer risk. Cervical liquid-based cytology (LBC), commonly known as Pap test, provides an accessible gynecological sample to test the value of TP53 somatic mutations as a biomarker for high-grade serous ovarian cancer (HGSC), a cancer type mostly driven by TP53 mutations. We used ultra-deep duplex sequencing to analyze TP53 mutations in LBC and blood samples from 70 individuals (30 with and 40 without HGSC) undergoing gynecologic surgery, 30 carrying BRCA1 or BRCA2 germline pathogenic variants (BRCApv). Only 30% of the tumor mutations were found in LBC samples. However, TP53 pathogenic mutations were identified in nearly all LBC and blood samples, with only 5.4% of mutations in LBC (20/368) also found in the corresponding blood sample. TP53 mutations were more abundant in LBC than in blood and increased with age in both sample types. BRCApv carriers with HGSC had more TP53 clonal expansions in LBC than BRCApv carriers without cancer. Our results show that, while not useful for direct cancer detection, LBC samples capture TP53 mutation burden in the gynecological tract, presenting potential value for cancer risk assessment in individuals at higher hereditary risk for ovarian cancer.