Navigating Uncertainty in Clinical Practice: A Workshop to Prepare Medical Students to Problem-Solve During Complex Clinical Challenges.

Introduction: Uncertainty is an inherent part of medicine. Prior work has trained medical students to better communicate diagnostic uncertainty; however, this work touches on only one aspect of the uncertainty students will face in practice. We developed a session to provide them with a taxonomy for categorizing the various types of uncertainty, as well as a framework to apply when navigating uncertainty during clinical challenges. These tools can help students make sense of uncertainty and determine actions in a complex health system. Methods: We designed a virtual workshop for third-year medical students at the end of their core clerkships. It included a didactic session followed by a small-group immersive unfolding case experience with several challenge points during which we tasked students with applying the framework, classifying the uncertainty domain, and discussing how they would problem-solve each scenario. Results: We conducted the workshop with 128 third-year medical students. We collected data through an anonymous postsession survey (86% response rate; 110 of 128 students). Most found the workshop useful (64%; 54 of 85), and a large number found the framework helpful in appraising uncertainty (47%; 42 of 89). A majority felt their perspectives on uncertainty changed after the workshop (66%; 73 of 110). Students integrated prior health systems science knowledge in their strategies to problem-solve each challenge. Discussion: This session provides a novel application of a sense-making framework and taxonomy for medical students to classify uncertainty. It offers a simple, low-cost, interactive, virtual activity that can be implemented at other institutions.

Intolerance of uncertainty and attitudes towards persons living with disabilities in medical students: Is there a correlation?

Introduction: Patients living with a disability experience an illness trajectory that may be uncertain. While navigating clinical uncertainty has been well-researched, health professionals' intolerance of uncertainty for patients living with disabilities has yet to be explored. We examined the relationship between medical students' intolerance of uncertainty with their attitudes towards people living with disabilities to better inform curricular efforts. Methods: We employed a survey-based design consisting of the Intolerance of Uncertainty Scale (IUS) and Disability Attitudes in Healthcare (DAHC) Scale to medical students upon completion of core clerkships (end of third-year of training). Data were de-identified. Mean DAHC and IUS scores were compared with published values via t-test. Linear regression was used to examine IUS/DAHC scores for anonymized students. Pearson correlation coefficient was calculated to assess correlation between IUS and DAHC scores. Results: Response rate was 97% (268/275 students). Mean IUS score did not differ from previously cited medical student scores, but mean DAHC score was significantly higher than previously cited scores. We observed a statistically-significant relationship between IUS and DAHC scores. Students with greater intolerance of uncertainty had lower scores for disability attitudes [F(1,243) = 8.05, value of p < 0.01], with an R 2-value of 0.032, suggesting that 3% of DAHC score variance can be explained by IUS score changes. Conclusion: We identified a weak negative correlation between IUS and DAHC scores in medical students. Further research is needed to clarify findings and identify best practices that equip trainees with skills to care for patients with uncertain illness trajectories and patients living with disabilities.

Phase II Single-arm Study of Durvalumab and Tremelimumab with Concurrent Radiotherapy in Patients with Mismatch Repair-proficient Metastatic Colorectal Cancer.

PURPOSE: Immune checkpoint inhibition (ICI) alone is not active in mismatch repair-proficient (MMR-P) metastatic colorectal cancer (mCRC), nor does radiotherapy alone result in objective systemic benefit. However, combined radiotherapy plus ICI can induce systemic antitumor immunity in preclinical and clinical models. PATIENTS AND METHODS: In this single-center, phase II study, patients with chemotherapy-refractory MMR-P mCRC received durvalumab 1,500 mg plus tremelimumab 75 mg every 4 weeks plus radiotherapy. The primary endpoint was objective response rate (ORR) in nonirradiated lesions. Treatment and efficacy were correlated with peripheral immune cell profiles. RESULTS: We enrolled 24 patients, and report outcomes after a median follow-up of 21.8 (range: 15.9-26.3) months. The ORR was 8.3% (2 patients) [95% confidence interval (CI), 1.0-27.0]. The median progression-free survival was 1.8 (95% CI, 1.7-1.9) months, median overall survival was 11.4 (95% CI, 10.1-17.4) months. Twenty five percent of patients (n = 6) had treatment-related grade 3-4 adverse events. We observed increased circulating CD8+ T lymphocyte activation, differentiation, and proliferation in patients with objective response. CONCLUSIONS: This combination of radiotherapy plus ICI study did not meet the prespecified endpoint criteria to be considered worthwhile for further study. However, rare instances of systemic immune augmentation and regression in nonirradiated lesions were observed (an abscopal response). Combination durvalumab and tremelimumab plus radiotherapy is feasible in MMR-P mCRC with a manageable safety profile. Further studies of novel immunotherapy combinations, and identification of biomarkers predictive of abscopal response are warranted.