Uptake of Cancer Genetic Services for Chatbot vs Standard-of-Care Delivery Models: The BRIDGE Randomized Clinical Trial.

Importance: Increasing numbers of unaffected individuals could benefit from genetic evaluation for inherited cancer susceptibility. Automated conversational agents (ie, chatbots) are being developed for cancer genetics contexts; however, randomized comparisons with standard of care (SOC) are needed. Objective: To examine whether chatbot and SOC approaches are equivalent in completion of pretest cancer genetic services and genetic testing. Design, Setting, and Participants: This equivalence trial (Broadening the Reach, Impact, and Delivery of Genetic Services [BRIDGE] randomized clinical trial) was conducted between August 15, 2020, and August 31, 2023, at 2 US health care systems (University of Utah Health and NYU Langone Health). Participants were aged 25 to 60 years, had had a primary care visit in the previous 3 years, were eligible for cancer genetic evaluation, were English or Spanish speaking, had no prior cancer diagnosis other than nonmelanoma skin cancer, had no prior cancer genetic counseling or testing, and had an electronic patient portal account. Intervention: Participants were randomized 1:1 at the patient level to the study groups at each site. In the chatbot intervention group, patients were invited in a patient portal outreach message to complete a pretest genetics education chat. In the enhanced SOC control group, patients were invited to complete an SOC pretest appointment with a certified genetic counselor. Main Outcomes and Measures: Primary outcomes were completion of pretest cancer genetic services (ie, pretest genetics education chat or pretest genetic counseling appointment) and completion of genetic testing. Equivalence hypothesis testing was used to compare the study groups. Results: This study included 3073 patients (1554 in the chatbot group and 1519 in the enhanced SOC control group). Their mean (SD) age at outreach was 43.8 (9.9) years, and most (2233 of 3063 [72.9%]) were women. A total of 204 patients (7.3%) were Black, 317 (11.4%) were Latinx, and 2094 (75.0%) were White. The estimated percentage point difference for completion of pretest cancer genetic services between groups was 2.0 (95% CI, -1.1 to 5.0). The estimated percentage point difference for completion of genetic testing was -1.3 (95% CI, -3.7 to 1.1). Analyses suggested equivalence in the primary outcomes. Conclusions and Relevance: The findings of the BRIDGE equivalence trial support the use of chatbot approaches to offer cancer genetic services. Chatbot tools can be a key component of sustainable and scalable population health management strategies to enhance access to cancer genetic services. Trial Registration: ClinicalTrials.gov Identifier: NCT03985852.

Neuro-Ophthalmologic Variability in Presentation of Genetically Confirmed Wolfram Syndrome: A Case Series and Review.

Wolfram syndrome is a neurodegenerative disorder caused by pathogenic variants in the genes WFS1 or CISD2. Clinically, the classic phenotype is composed of optic atrophy, diabetes mellitus type 1, diabetes insipidus, and deafness. Wolfram syndrome, however, is phenotypically heterogenous with variable clinical manifestations and age of onset. We describe four cases of genetically confirmed Wolfram syndrome with variable presentations, including acute-on-chronic vision loss, dyschromatopsia, and tonic pupils. All patients had optic atrophy, only three had diabetes, and none exhibited the classic Wolfram phenotype. MRI revealed a varying degree of the classical features associated with the syndrome, including optic nerve, cerebellar, and brainstem atrophy. The cohort's genotype and presentation supported the reported phenotype-genotype correlations for Wolfram, where missense variants lead to milder, later-onset presentation of the Wolfram syndrome spectrum. When early onset optic atrophy and/or diabetes mellitus are present in a patient, a diagnosis of Wolfram syndrome should be considered, as early diagnosis is crucial for the appropriate referrals and management of the associated conditions. Nevertheless, the condition should also be considered in otherwise unexplained, later-onset optic atrophy, given the phenotypic spectrum.

Barriers to family history collection among Spanish-speaking primary care patients: a BRIDGE qualitative study.

Objectives: Family history is an important tool for assessing disease risk, and tailoring recommendations for screening and genetic services referral. This study explored barriers to family history collection with Spanish-speaking patients. Methods: This qualitative study was conducted in two US healthcare systems. We conducted semi-structured interviews with medical assistants, physicians, and interpreters with experience collecting family history for Spanish-speaking patients. Results: The most common patient-level barrier was the perception that some Spanish-speaking patients had limited knowledge of family history. Interpersonal communication barriers related to dialectical differences and decisions about using formal interpreters vs. Spanish-speaking staff. Organizational barriers included time pressures related to using interpreters, and ad hoc workflow adaptations for Spanish-speaking patients that might leave gaps in family history collection. Conclusions: This study identified multi-level barriers to family history collection with Spanish-speaking patients in primary care. Findings suggest that a key priority to enhance communication would be to standardize processes for working with interpreters. Innovation: To improve communication with and care provided to Spanish-speaking patients, there is a need to increase healthcare provider awareness about implicit bias, to address ad hoc workflow adjustments within practice settings, to evaluate the need for professional interpreter services, and to improve digital tools to facilitate family history collection.

Association of Disparities in Family History and Family Cancer History in the Electronic Health Record With Sex, Race, Hispanic or Latino Ethnicity, and Language Preference in 2 Large US Health Care Systems.

Importance: Clinical decision support (CDS) algorithms are increasingly being implemented in health care systems to identify patients for specialty care. However, systematic differences in missingness of electronic health record (EHR) data may lead to disparities in identification by CDS algorithms. Objective: To examine the availability and comprehensiveness of cancer family history information (FHI) in patients' EHRs by sex, race, Hispanic or Latino ethnicity, and language preference in 2 large health care systems in 2021. Design, Setting, and Participants: This retrospective EHR quality improvement study used EHR data from 2 health care systems: University of Utah Health (UHealth) and NYU Langone Health (NYULH). Participants included patients aged 25 to 60 years who had a primary care appointment in the previous 3 years. Data were collected or abstracted from the EHR from December 10, 2020, to October 31, 2021, and analyzed from June 15 to October 31, 2021. Exposures: Prior collection of cancer FHI in primary care settings. Main Outcomes and Measures: Availability was defined as having any FHI and any cancer FHI in the EHR and was examined at the patient level. Comprehensiveness was defined as whether a cancer family history observation in the EHR specified the type of cancer diagnosed in a family member, the relationship of the family member to the patient, and the age at onset for the family member and was examined at the observation level. Results: Among 144 484 patients in the UHealth system, 53.6% were women; 74.4% were non-Hispanic or non-Latino and 67.6% were White; and 83.0% had an English language preference. Among 377 621 patients in the NYULH system, 55.3% were women; 63.2% were non-Hispanic or non-Latino, and 55.3% were White; and 89.9% had an English language preference. Patients from historically medically undeserved groups-specifically, Black vs White patients (UHealth: 17.3% [95% CI, 16.1%-18.6%] vs 42.8% [95% CI, 42.5%-43.1%]; NYULH: 24.4% [95% CI, 24.0%-24.8%] vs 33.8% [95% CI, 33.6%-34.0%]), Hispanic or Latino vs non-Hispanic or non-Latino patients (UHealth: 27.2% [95% CI, 26.5%-27.8%] vs 40.2% [95% CI, 39.9%-40.5%]; NYULH: 24.4% [95% CI, 24.1%-24.7%] vs 31.6% [95% CI, 31.4%-31.8%]), Spanish-speaking vs English-speaking patients (UHealth: 18.4% [95% CI, 17.2%-19.1%] vs 40.0% [95% CI, 39.7%-40.3%]; NYULH: 15.1% [95% CI, 14.6%-15.6%] vs 31.1% [95% CI, 30.9%-31.2%), and men vs women (UHealth: 30.8% [95% CI, 30.4%-31.2%] vs 43.0% [95% CI, 42.6%-43.3%]; NYULH: 23.1% [95% CI, 22.9%-23.3%] vs 34.9% [95% CI, 34.7%-35.1%])-had significantly lower availability and comprehensiveness of cancer FHI (P < .001). Conclusions and Relevance: These findings suggest that systematic differences in the availability and comprehensiveness of FHI in the EHR may introduce informative presence bias as inputs to CDS algorithms. The observed differences may also exacerbate disparities for medically underserved groups. System-, clinician-, and patient-level efforts are needed to improve the collection of FHI.

Lynch Syndrome-Associated Variants and Cancer Rates in an Ancestrally Diverse Biobank.

PURPOSE: Limited data are available on the prevalence and clinical impact of Lynch syndrome (LS)-associated genomic variants in non-European ancestry populations. We identified and characterized individuals harboring LS-associated variants in the ancestrally diverse BioMe Biobank in New York City. PATIENTS AND METHODS: Exome sequence data from 30,223 adult BioMe participants were evaluated for pathogenic, likely pathogenic, and predicted loss-of-function variants in MLH1, MSH2, MSH6, and PMS2. Survey and electronic health record data from variant-positive individuals were reviewed for personal and family cancer histories. RESULTS: We identified 70 individuals (0.2%) harboring LS-associated variants in MLH1 (n = 12; 17%), MSH2 (n = 13; 19%), MSH6 (n = 16; 23%), and PMS2 (n = 29; 41%). The overall prevalence was 1 in 432, with higher prevalence among individuals of self-reported African ancestry (1 in 299) than among Hispanic/Latinx (1 in 654) or European (1 in 518) ancestries. Thirteen variant-positive individuals (19%) had a personal history, and 19 (27%) had a family history of an LS-related cancer. LS-related cancer rates were highest in individuals with MSH6 variants (31%) and lowest in those with PMS2 variants (7%). LS-associated variants were associated with increased risk of colorectal (odds ratio [OR], 5.0; P = .02) and endometrial (OR, 30.1; P = 8.5 × 10-9) cancers in BioMe. Only 2 variant-positive individuals (3%) had a documented diagnosis of LS. CONCLUSION: We found a higher prevalence of LS-associated variants among individuals of African ancestry in New York City. Although cancer risk is significantly increased among variant-positive individuals, the majority do not harbor a clinical diagnosis of LS, suggesting underrecognition of this disease.