Calibrating variant curation by clinical context based on factors that influence patients' tolerance of uncertainty.

PURPOSE: Shared decision making manages genomic uncertainty by integrating molecular and clinical uncertainties with patient values to craft a person-centered management plan. Laboratories seek genomic report consistency, agnostic to clinical context. Molecular reports often mask laboratory-managed uncertainties from clinical decision making. Better integration of these uncertainty management strategies requires a nuanced understanding of patients' perceptions and reactions to test uncertainties. We explored patients' tolerance to variant uncertainty in 3 parameters: (1) relative causal significance, (2) risk accuracy, and (3) classification validity. METHOD: Deliberative forums were undertaken with 18 patients with predictive testing experience. Uncertainty deliberations were elicited for each parameter. A thematic framework was first developed, and then mapped to whether they justified tolerance to more or less parameter-specific uncertainty. RESULTS: Six identified themes mapped to clinical and personal domains. These domains generated opposing forces when calibrating uncertainty. Personal themes justified tolerance of higher uncertainty and clinical themes lower uncertainty. Decision making in uncertainty focused on reducing management regret. Open communication increased tolerance of classification validity and risk accuracy uncertainty. Using these data, we have developed a nascent clinical algorithm integrating molecular uncertainty with clinical context through a targeted communication framework. CONCLUSION: Maximizing test utility necessitates context-specific recalibration of uncertainty management and communication.

Knowledge of Required Medical Surveillance Among Adolescent and Young Adult Survivors of Childhood Cancer.

PURPOSE: Adolescent and young adult (AYA) cancer survivors experience treatment-related late effects so guidelines recommend providing a treatment summary, yearly follow-up, and risk-adapted testing. AYA survivors' knowledge of surveillance follow-up was studied. RESULTS: Survey responses for 73 AYAs were stratified: low (0 to 1 correct; n=18; 24.7%) versus high knowledge (2 to 4 correct; n=55; 75.3%) of their required testing. Patient-reported Outcomes Measurement Information System (PROMIS) scores fell within average ranges for participant age ( T -scores: 52.4 for physical function, 49.3 for anxiety, 46.3 for depression, and 44.7 for fatigue). Younger age at survivorship visit was a significant predictors of improved knowledge scores. CONCLUSION: Despite attendance at a survivorship clinic, minority of participants (9.5%) demonstrated complete knowledge of surveillance testing needs. Most survivors are aware of some of their surveillance needs. PROMIS scores were not associated with surveillance knowledge.

Hemoglobin S/Hemoglobin Quebec-Chori Presenting as Sickle Cell Disease: A Case Report.

BACKGROUND: Sickle cell disease is a homozygous hemoglobinopathy with vaso-occlusive complications secondary to abnormal sickling of red blood cells under stressful conditions such as hypoxia. Children with sickle cell trait have a heterozygous genetic state, typically without symptoms. OBSERVATION: An 8-year-old boy diagnosed with sickle cell trait was found to have multiple complications consistent with sickle cell disease, including pain crises, osteomyelitis, and priapism. Over a 6-year period, he underwent routine laboratory evaluations without a definitive diagnosis. The diagnosis of a compound heterozygous state of hemoglobin S/hemoglobin Quebec-Chori was eventually made on the basis of mass spectrometry and confirmed with hemoglobin subunit beta gene sequencing. CONCLUSION: Expanding diagnostic evaluation in patients with abnormal clinical presentations is vital to making the correct diagnosis and hence earlier institution of appropriate management of rare hemoglobinopathies.