Abstract:

The purpose of this study was to understand the perspectives of genetics and nongenetics professionals regarding the gaps in rapid whole genome sequencing (rWGS) education and current challenges to workflow. The aim was to develop a toolkit for inpatient medical professionals to guide their understanding of rWGS, hospital workflow, patient eligibility, consent, and results. Methods: The toolkit was developed based on a thematic analysis of semi-structured interviews with genetic counselors (n=3), neonatologists (n=2), a nurse educator, and bedside nurses (n=3) at Valley Children’s Hospital. The themes elucidated from this analysis helped me identify areas in which the rWGS process and understanding of the technology could be improved. I also conducted a literature review that guided my understanding of the challenges of implementing new technologies, a laboratory website review that allowed me to evaluate the information on rWGS that is readily available, and an analysis of existing educational materials for other genetic tests to inform the depth of information, language, and organization needed for basic educational materials. Results: The thematic analysis of the interviews along with the reviews revealed the following: a need for an improved understanding of rWGS testing (what it is, what it looks at, when is it appropriate, and who is eligible), timing (when should genetics be consulted and test turnover time), the consent process (what constitutes informed consent), and potential results. These needs informed the development of materials that can be integrated into existing training modules or used as stand-alone resources. Conclusion: This work identified a need for improved education on rWGS for inpatient providers and medical staff. The toolkit developed to address this need contains educational materials that target different areas in which the understanding of rWGS can be improved. Continued research and initiatives to refine these materials and tailor them to the needs of specialty departments and initiatives to refine these materials and tailor them to the needs of specialty departments within the hospital will be essential to improving the overall rWGS workflow and experience for the staff and patients alike.

Abstract:

Patients often find it challenging to comprehend genetic testing lab reports. Efforts to simplify these reports and provide additional resources to interpret test results have shown promise in improving patient understanding and decision-making. This project extends previous work by implementing a lab report guide to assist patients in interpreting genome sequencing results, particularly in the context of the 21st Century Cures Act. A qualitative approach was used to evaluate the utility of the lab report guide. Participants were recruited from an ongoing study at UCSF, where they underwent genome sequencing for their fetuses with anomalies identified by ultrasound. Participants received their results via the "MyChart" patient portal and subsequently discussed them with a genetic counselor. Semi-structured interviews were conducted to explore their experiences with the guide, emotional responses to the results, and the impact of genetic counseling. Thematic analysis was employed to identify key themes from six interviews. Four main themes emerged: (1) Emotional reaction to results, (2) Interpretation of results, (3) Utility and feedback on the lab report guide, and (4) Impact of genetic counseling. Participants appreciated the user-friendly format and detailed explanations in the guide and valued the genetic counseling session for clarification and support. This project highlights the importance of providing user-friendly resources to help patients interpret genetic test results, especially in the context of the 21st Century Cures Act. The feedback on the lab report guide suggests its potential for broader implementation. Future research should focus on integrating such resources into electronic health records and exploring their impact on both patients and providers. As genetic testing becomes more common, equipping patients with tools like the lab report guide will be crucial for helping them understand their results and make informed decisions. 

Abstract:

The landscape of genetic counseling has shifted towards telehealth, reflecting broader trends in healthcare delivery, particularly in the wake of the COVID-19 pandemic. This transition has sparked discussions on the efficacy and challenges of telehealth, especially in the context of genetic counseling specialties. Drawing on semi-structured interviews, this study examines provider perspectives on telehealth effectiveness across cancer, prenatal, and pediatric genetic counseling specialties. Themes identified mirror prior studies, with providers acknowledging telehealth's benefits in increasing access to genetic services while also noting technical and logistical limitations. Additionally, specialty-specific nuances emerged, with the cancer specialty showing great adaptation from in-person to telehealth while prenatal and pediatric specialties both exhibited limitations that require addressing before telehealth encounters can be better optimized. These findings underscore the importance of a hybrid model that combines in-person and telehealth sessions, tailored to the needs of each specialty. Recommendations are made to optimize telehealth outcomes, ensuring that genetic counseling continues to provide nuanced care across diverse patient populations.

Abstract:

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition with a significant genetic component. One intriguing subtype of ASD, Maternal Autoantibody Related (MAR-ASD), is associated with the presence of maternal autoantibodies interacting with fetal brain antigens during pregnancy. However, the genetic and population-specific factors influencing development of these autoantibodies remain understudied. This study utilized a genome-wide association study from the Early Markers for Autism (EMA) cohort, comprising pregnant women with diverse genetic ancestries (European, Hispanic, and Asian). The preliminary findings reveal associations between certain single nucleotide polymorphisms (SNPs) and antibody patterns, with notable population-specific differences in these associations. Potential explanations include: a) linkage disequilibrium (LD) differences, b) allele frequency differences, or c) nongenetic (environmental) differences. Identification of LD proxy SNPs, examining allele frequency differences, local ancestry inference, and principal components analysis were used to parse out the ancestral differences observed. LD analysis failed to identify SNPs showing cross-ancestry associations. Allele frequency analysis highlighted SNPs exhibiting differential allele frequencies across ancestries, potentially contributing to ancestry-specific associations. Furthermore, local ancestry inference provided insights into the hidden variation or combinations of variants associated with the association differences. Principal components analysis (PCA) did not reveal differences between antibody positive and negative individuals in expected directions. Overall, our study underscores the importance of considering genetic and population-specific factors in understanding MAR-ASD. These findings highlight the need for further investigation into the intricate interplay of genetics, environment, and ancestry in ASD etiology.

Abstract:

Diversity is crucial in the healthcare field, including genetic counseling, due to its numerous benefits and positive impact on patient outcomes. The demographic composition of the genetic counseling profession has been a persisten area of concern as it is predominantly white. Using surveys and semi-structured interviews with DEIJ group leaders and conducting a preliminary GC program website content analysis, the study aimed to comprehensively explore organizational strategies and outcomes to capture nuanced experiences from both genetic counseling programs and grassroots organizations. Results showed that a minority of genetic counseling programs had DEIJ content on their program website (25/60, 41.7%), and even fewer claimed to have a DEIJ group on their website (4/60, 6.7%). Six major themes emerged from the semi-structured interviews: group structure, connection to other DEIJ groups, self-assessment, centralized platform, organizational models, and passion for DEIJ work. Recent events, including the U.S. Supreme Court's June 2023 decision to end affirmative action in higher education have brought DEIJ effots to the forefront once again. As colleges eliminate DEIJ programs adn statements, it becomes crucial to understand their impact on increasing diversity within the GC profession. There is a need for more research on how DEIJ principles and activities have been incorporated into genetic counseling programs and its impact on diversifying the field. 

Abstract:

Understanding patient and provider preferences for in-person appointments after the COVID-19 pandemic is critical for clinical planning and patient experience. Recent studies conducted during the pandemic highlight that telehealth appointments are effective across various specialties. However, information about visit type preferences post-pandemic is lacking. We conducted a quality improvement study to assess patient and provider preferences for in-person and remote appointments. Participants include adult and pediatric patients seen for the first time at the University of California, San Francisco, Division of Medical Genetics. From the responses of 104 patients and 11 genetics providers, results revealed that more patients prefer an in-person appointment than is currently offered (P<0.001). Preferences for many patients were guided by the necessity and perceived benefit of a physical exam, and is the only portion of a visit that is preferred by patients and providers to be conducted in person (P<0.05). These findings suggest that medical genetics clinics may benefit from creating additional in-person appointments to meet patient demand. This data will contribute to the understanding of in-person genetics appointment preferences in a post-pandemic environment.

Abstract:

Sex chromosome aneuploidies (SCAs), also called X and Y variations, are chromosome conditions with variable phenotypes. With the increasing prevalence of prenatal screening for SCAs, it is imperative to incorporate perspectives from individuals with these conditions into policy, guidelines, and educational materials. To fill this gap, we conducted exploratory qualitative research with adults with X&Y chromosome variations. We conducted thirteen semi-structured interviews with individuals with a diagnosis of 47,XXY, 47,XXX, and 47,XYY. The interviews covered participants' perspectives on prenatal screening, communication with providers, and the impact of receiving a diagnosis. The study offers significant insights into the impact of X and Y variations on individuals' lives, effective communication strategies for healthcare providers, and perspectives on prenatal screening for these conditions. Participants commonly described receiving their diagnosis as essential for making meaning of their symptoms and positively impacting their self-esteem. Participants emphasized the importance of feeling supported and understood by healthcare providers, highlighting the need for improved provider education about X&Y variations. While participants generally opposed termination for X&Y variations, they acknowledged potential benefits of prenatal screening, such as increased time for parents to educate themselves and access to early intervention. However, the disconnect between perceived benefits and available resources for early intervention highlights a critical gap in healthcare provision. Overall, the study highlights the need for changing medical practices and communication with a focus on positive framing and greater connection to resources for individuals with X&Y variations.

Abstract:

The goal of this chart review study was to explore patient recontact after an initial variant of uncertain significance (VUS) result was received in the cardiovascular genetics setting. Much
of the previous literature on this subject has been limited to the hereditary cancer setting. We
examined the rate of reclassification for VUSs in the cardiovascular genetic setting, types of
reclassifications, and how the rate of reclassification varied by type of cardiogenetic condition or
by demographic group. The mode of communication when a reclassification occurred and impact
on the patient’s medical management was also investigated. Our study found that most
reclassifications are initiated by the laboratory testing company. Significant differences were
seen in the time to VUS reclassification between male and female patients, as well as by the year
that the initial testing was ordered. Overall, the time to variant reclassification in the
cardiovascular genetics setting appears to be longer in comparison to previous studies in other
specialties. There was no consistent mode of communication used to notify patients that their
VUS had been reclassified. As changes to medical management in the cardiovascular setting can
be critical to the patient and family members’ health, we also analyzed ways in which VUS
reclassification impacted patient’s management. These included prompting advice about
reproductive implications/options, additional testing for the patient and family members, and one
instance of a medication recommendation. However, most VUSs were not reclassified, and of
those that were, the minority impacted medical management. We hope this study can help
cardiology genetic counselors set expectations with patients regarding their VUS results and help
guide a future quality improvement project to develop a workflow of communicating
reclassifications and monitoring VUSs.

Abstract:

Expanded carrier screening (ECS) provides information for individuals about their carrier status for multiple inherited genetic conditions. This information can be used by individuals to make reproductive decisions and to better understand potential risks to their offspring. This technology has allowed for the identification of reproductive pairs who are at-risk for inherited genetic conditions. Currently, there are conflicting professional guidelines around expanded carrier screening and numerous labs offer widely varying panel options that are all considered ECS. It is hypothesized that these factors make it challenging for genetic counselors to have consistent practices around ordering expanded carrier screening. This study aimed to survey genetic counselors in the United States on their personal practices related to ECS, their institutional guidance around ECS, and their thoughts and needs on the practice. This was accomplished through an online survey consisting of open and closed questions. A total of 143 responses were collected.Participants reported the following differences: number of genes ordered in their standard panel, how they handled the reproductive partner’s testing, and how they determined if a patient should be offered ECS or standard carrier screening. Additionally, institutional guidelines varied by whether a guideline existed, practices around which panels to order, and which providers at that institution order the testing. Participants described considerations including variance in insurance coverage, thoughts of equity, and the utility of the current testing strategy. These responses highlighted the varying practices of ECS around the country that are thought to translate to differing patient experiences. There is an ongoing need to reach a professional consensus regarding ECS, so it is being used effectively and equitably.

Abstract:

Sickle Cell Disease (SCD) is diagnosed in every 1 in 365 African American births. The molecular mechanism of SCD was established in 1949, but treatments have been slow to develop. Four drug therapies and bone marrow transplantation are approved by the Food Drug Administration (FDA) to treat SCD, but uptake and long-term utilization is low. As of December of 2023, there are two gene therapies that are FDA-approved to treat Sickle Cell Disease also. Previous research identified barriers to care and facilitators of decision making using quantitative methods or focus groups. There is limited data available that uses qualitative methods to understand the lived experience of SCD and how that experience may influence attitudes, perceptions, and decision-making surrounding disease-modifying therapies. The literature also lacks information that comes from pediatric patients themselves. The aim of this study was to fill that gap. Semi-structured interviews with pediatric patients and parents identified themes that can inform clinicians and researchers about this community’s concerns, hopes, and experience of SCD and its treatment options. Three themes were identified by thematic analysis of transcripts: 1) SCD is a Dynamic Lifelong Disease, 2) Facilitators of Decision Making, and 3) Barriers to Care. Each theme had related subthemes identified. Information about symptoms, treatments, disease knowledge, and lifestyle were also revealed. These findings can be used to improve SCD care and treatment with the goal of reducing disease burden and improving quality of life. 

Abstract:

This study aimed to evaluate the concordance of genetic ancestry reports from different providers, assess the accuracy of genetic ancestry compared to self-identified race and ethnicity (SIRE), and explore patient and provider perspectives on the potential utility and integration of genetic ancestry data into the electronic health record (EHR). METHODS: Genetic ancestry results from two commercial providers and two 3rd-party analyses were compared for concordance using data from 451 participants in the UCSF 3D Health Study. Genetic ancestry was also compared to SIRE. Surveys were administered to gather perspectives on genetic ancestry testing, its accuracy, and potential integration into the EHR.  
RESULTS: The overall mean concordance between the two commercial providers was 58.41%. Ancestry from one provider had the highest concordance with SIRE, ranging from 80.05% to 94.78% across different thresholds. The majority of participants and providers were neutral regarding the integration of genetic ancestry into the EHR.  CONCLUSION: Significant discordance exists between genetic ancestry reports from different providers, highlighting the need for standardization in the calculation of genetic ancestry. While participants and providers acknowledge the potential utility of genetic ancestry in personalized medicine, concerns regarding data privacy, accuracy, and the potential for discrimination must be addressed before integration into the EHR.  

Abstract:

The National Comprehensive Cancer Network (NCCN) guidelines recommend that anyone with pathogenic BRCA1/2 mutations on somatic testing be recommended follow up germline testing. This study aims to investigate whether or not patients who were identified to have BRCA1/2 pathogenic mutations on UCSF500 somatic tumor testing received recommendations for follow up germline testing. This study retrospectively reviewed medical records of patients who received pathogenic BRCA1/2 mutation results during 2022 on their UCSF500 somatic testing to identify the patients who did or did not receive follow up. Baseline characteristics such as sex, age, and ethnicity were collected and statistical analysis, including a multivariable logistic regression model, was performed to associate these characteristics with rate of germline follow up. Of the 114 patients who were identified as having pathogenic or likely pathogenic BRCA1/2 mutations in 2022 on UCSF500 assay testing, 71 received some type of follow up recommendations (62%). Of the 71 that received some form of follow up, 31 tested positive for germline BRCA1/2 mutations (44%). This study identified a discrepancy between patients who should receive follow up germlines testing and those who actually receive follow up. This highlights a continued need for further education and the creation of a standardized protocol to manage incidental germline findings that are identified through somatic tumor testing.