A New Registry for Genetic Diagnosis of Inborn Errors of Immunity within the Military Health System

Genotypic definition of monogenic inborn errors of immunity (IEIs) continues to accelerate with broader access to next generation sequencing, underscoring this aggregated group of disorders as a major health burden impacting both civilian and military populations. At an estimated prevalence of 1 in 1200 individuals, IEIs affect ~8,000 patients within the Military Health System (MHS). Despite access to targeted gene/exome panels at military treatment facilities, most affected patients never receive a definitive genetic diagnosis that would significantly improve clinical care. To address this gap, we established the first registry of IEI patients within the MHS with the goal of identifying known and novel pathogenic genetic defects to increase diagnosis rates and enhance clinical care. Using the registry, a research protocol was opened in July 2022. Since July we have enrolled 75 IEI patients encompassing a breadth of phenotypes including severe and recurrent infections, bone marrow failure, autoimmunity/autoinflammation, atopic disease, and malignancy. Enrolled patients provide blood and bone marrow samples for whole genome, ultra-deep targeted panel and comprehensive transcriptome sequencing, plus cryopreservation of peripheral blood mononuclear cells for future functional studies. We are also implementing and developing analytical methods for identifying and interrogating non-coding and structural variants. Suspected pathogenic variants are adjudicated by a clinical molecular geneticist using state-of-the-art analysis pipelines. These analyses subsequently inform in vitro experiments to validate causative mutations using cell reporter systems and primary patient cells. Clinical variant validation and return of genetic results are planned with genetic counseling provided. As a proof of principle, this integrated genetic evaluation pipeline revealed a novel, candidate TLR7 nonsense variant in two adolescent brothers who both endured critical COVID-19 pneumonia, requiring mechanical ventilation and extracorporeal membrane oxygenation. Our protocol is therefore poised to greatly enrich clinical genetics resources available in the MHS for IEI patients, contributing to better diagnosis rates, informed family counseling, and targeted treatments that collectively improve the health and readiness of the military community. Moreover, our efforts should yield new mechanistic insights on immune pathogenesis for a broad variety of known and novel IEIs.Copyright © 2023 Elsevier Inc.

Genotype-phenotype correlations in five patients harboring SERPINA1 mutations and previously showing a severe COVID-19 infection

Background/Objectives: During COVID-19 pandemic, it is essential to detect patients potentially at risk of life-threatening complications, due to possible specific genetic mutations. The aim of our work is to show a practical application of genetic testing, allowing a diagnosis of alpha 1 antitrypsin deficiency in cases with a severe clinical course during COVID-19 infection. Method(s): During hospitalization for COVID-19, we identified 5 patients (3 female, 2 males from two different families, age range 18-47 years) with a severe course of COVID-19 infection, requiring high pressure ventilation with high volume oxygen supply. Two months after discharge, those patients were reevaluated with respiratory function tests, biochemical tests, genetic counselling and genetic testing. A peripheral blood sampling for SERPINA1 genetic testing has been performed, using Sanger sequencing. Result(s): Two months after discharge, in all 5 patients respiratory function tests were consistent with a dysventilatory obstructive syndrome, in contrast with usual findings related to COVID-19 infection. Blood test still showed increase plasmatic transaminase concentration in 3 out of 5 patients, one having increased serum bilirubin as well. We performed SERPINA1 genetic testing showing homozygosity for SERPINA1 pathogenic mutations (c.193del and c.875C>T, respectively) in all 5 patients. Conclusion(s): These cases showed the importance of genetic testing for patients with unexplained severe COVID-19 infection. Genetic testing allowed the diagnosis of cases affected by alpha 1 antitrypsin deficiency, associated with dysventilatory obstructive syndrome, that may worsen the short and long term prognosis of COVID-19.

Patient and Provider Experiences and Views on the Use of Telehealth in Genetics Clinics in Response to the COVID-19 Pandemic.

Introduction: The 2019 Coronavirus Disease (COVID-19) pandemic necessitated a mass transition in genetics clinics nationwide from in-person care to virtual care through telehealth. Before the COVID-19 pandemic, there was limited research on the use of telehealth in genetics specialties. Therefore, the COVID-19 pandemic presented a unique opportunity to study this emerging mode of care delivery in the setting of genetics clinics. This study described the scope of telehealth use in genetics clinics nationally and determined how COVID-19 influenced patients' decisions regarding their genetic care. Methods: Two anonymous surveys for patients and providers were developed. The patient survey was offered online to all genetics patients seen through telehealth at a Manhattan-based practice between March and December 2020. The provider survey was distributed through several listservs to genetics providers nationwide. Results: Patients (n = 242) and providers (n = 150) responded. Telehealth was used in all specialty genetics clinics for both initial and follow-up visits. Telehealth was both effective and satisfactory to patients for both visit types and across specialties; however, Asian and Hispanic/Latino patients had significantly lower mean satisfaction scores compared with White patients (p = 0.03 and 0.04, respectively). Patients appreciated telehealth for its convenience and to avoid COVID-19 exposure. Providers across specialties and provider types preferred telehealth for follow-up rather than initial visits. Several clinic initiatives related to telehealth were identified. Discussion: Telehealth was generally well received by both patients and providers, and is expected to become permanent option in genetics clinics. Further studies are needed to identify barriers to accessing telehealth.

Infantile spasms: guidance for pediatricians

In a cross-sectional study of 100 parents of children with infantile spasms, the median time from spasm onset to first visit with any health care provider was 5 days, but the median time from onset to first visit with an "effective provider" (one who provided both accurate diagnosis and prescription for appropriate first-line treatment) was 24 days,5 a delay attributed at least in part to poor awareness of the condition among providers.5 Given that worse outcomes may be associated with even a 1-week delay in treatment from onset, it is critical that pediatric health care providers are proficient in recognizing this condition.67 Clinical features Infantile spasms An infantile spasm is brief and abrupt, generally 1 to 3 seconds, with muscle contraction that can include the head, neck, trunk, and/or extremities. Home video recording, first advised by the Child Neurology Society to streamline IESS management at the onset of the COVID-19 pandemic, has since been endorsed as a continued recommendation toward timely intervention.4 In preparing to evaluate a patient with possible IESS, pediatricians should ask caregivers to record suspected events. The EEG pattern during the spasm itself is a high-amplitude sharp or slow wave followed by a relative electrodecrement. Because the interictal EEG is generally abnormal, it is not necessary to capture a spasm during the EEG recording to support the diagnosis. Workup for an underlying etiology if not known is important not only because some are associated with other health concerns requiring monitoring and intervention, but also because it can guide management, as some etiologies may respond better to different treatment approaches.9 Identification may also guide appropriate counseling of families, including prognostication and possible genetic counseling.

An Evolving Relationship Between Medical Oncologists and Genetic Counselors in Prostate Cancer

Important to the success of this model would likely be the degree of clinician experience (ie, how comprehensive their genetic counseling training has been), the clinician's comfort level, and the supporting staff or resources available to the clinician to operate a provider-led germline testing model.4 Members of a consensus panel discussing germline testing have pointed out that clinicians who lack genetics training may experience numerous obstacles when counseling patients, in particular obstacles related to limited knowledge of the downstream impact of genetic testing, such as health insurance coverage, implications for life insurance, and protections afforded by the Genetic Information Nondiscrimination Act.5 Discussions about the importance and management of variants of unknown significance could be confusing for the patient even in the posttesting stage without appropriate knowledge and training on the clinician's part. Mauer et al have described the value of virtual counseling and technological adaptations, including billing practices and coordination of education and outreach opportunities, that have been made during the pandemic and have helped genetic counselors.6 Such adaptations represent only a few of the evolving strategies that we as medical oncologists, in conjunction with our health care team, must seek out and implement to help our genetic counseling colleagues reach an expanding population of prostate cancer patients in need of evidence-based germline testing. Inherited DNA-repair gene mutations in men with metastatic prostate cancer.

Universal Genetic Counseling for Breast Cancer Patients Mitigates Social Determinants of Health and Improves Genetic Testing Rates Across All Races

INTRODUCTION: While available since 1996, genetic testing for breast cancer patients has been limited by stigma, cost, and poor access. Many patients were not captured by traditional NCCN criteria, particularly those with healthcare barriers. Previously, genetic testing was used in high-risk screening and determining prophylactic utility, but with recent targeted therapies, has allowed personalized therapeutic benefit for patients. We expanded genetic testing counseling at a three-hospital Midwestern community hospital system from only NCCN high-risk patients to all patients diagnosed with breast cancer. METHOD(S): The implementation of universal genetic counseling to all newly diagnosed breast cancer patients began at our system in 2020. Under IRB approval, all new breast cancer patients were retrospectively reviewed from January 2019 through December 2019 (genetics based on NCCN guidelines group) and January 2021 through December 2021 (genetics offered to all group). Patient data regarding completion of genetic testing, pathologic mutations identified, stage, race/ethnicity, insurance type, primary language, and age was included in the analysis. Categorical variables were compared using Pearson's chi-square or Fisher's exact test;age was analyzed using ANOVA. RESULT(S): We reviewed a total of 973 patients, 439 diagnosed in 2019 and 534 in 2021. Demographic differences between 2019 and 2021 were similar including age, race/ethnicity, insurance, primary language. Despite the SARS CoV-2 pandemic, the stage of diagnosis between 2019 and 2021 was also similar (p=0.194). Completion of genetic testing increased significantly from 204 (48.6%) in 2019 to 338 (63.3%) (p=0.000) in 2021 with the universal access group. Across all demographic groups, genetic testing increased with significant findings in Medicare patients (p=0.005) and older patients (p=0.041) and near significant findings in non-white populations (0.059).[Table] Overall number of pathological mutations increased, 32 (7.29% of all patients) in 2019 to 39 (7.30%) in 2021, with the most common being BRCA2 (n=11), CFTR (n=9), CHEK2 (n=8), and BRCA1 (n=6). CONCLUSION(S): Implementation of universal access to breast cancer genetic counseling allowed for a significant expansion in genetic testing completion and overall increase in pathological mutations found. We saw an increase within sub-populations that may have not been targeted by NCCN guidelines previously including older patients, minority groups, and varying insurance types. (Table Presented).

Society for Maternal-Fetal Medicine Special Statement: Telemedicine in obstetrics-quality and safety considerations.

The frequency of telemedicine encounters has increased dramatically in recent years. This review summarizes the literature regarding the safety and quality of telemedicine for pregnancy-related services, including prenatal care, postpartum care, diabetes mellitus management, medication abortion, lactation support, hypertension management, genetic counseling, ultrasound examination, contraception, and mental health services. For many of these, telemedicine has several potential or proven benefits, including expanded patient access, improved patient satisfaction, decreased disparities in care delivery, and health outcomes at least comparable to those of traditional in-person encounters. Considering these benefits, it is suggested that payers should reimburse providers at least as much for telemedicine as for in-person services. Areas for future research are considered.

DEVELOPMENT OF AN ADVANCED PRACTICE PROVIDER (APP) LED HIGH-RISK CANCER PREVENTION PROGRAM IN A COMMUNITY SETTING

Many individuals are at an increased risk for developing cancer due to their genetics, environmental factors, prior diagnoses, lifestyle or demographics. Disparities in healthcare access and available services further increase cancer risk in certain communities. The COVID pandemic exacerbated these disparities with decreases in cancer screening rates. Those at increased cancer risk may be eligible for earlier, more frequent, or enhanced screenings, genetic testing, preventive medications, or surgeries. The purpose was to highlight the development of a High-Risk Cancer Prevention Program led by advanced practice providers (APPs) within a community healthcare system that aims to reduce disparities in cancer care by targeting underserved areas and populations within the community. The program provides patient-centered care focused on improving outcomes by performing comprehensive genetic, medical, and lifestyle risk assessments across the continuum from preventative care through survivorship. APPs provide smoking cessation services and work in partnership with registered dieticians to provide nutrition counseling and with genetic counselors, bariatrics, primary care, and oncology to provide access to comprehensive services needed to address the patients individualized risk factors. Partnerships with local community organizations provide collaborative services in areas with disparate outcomes to promote cancer screening awareness, education about cancer risk factors, and facilitate entrance into the healthcare system. As part of a community healthcare system APPs are positioned to serve both urban and rural populations where there is greatest need. Impact of these activities are measured utilizing a database tracking the demographics of patients served, services provided, adherence to surveillance recommendations, testing performed, and outcomes including cancers detected. APPs are uniquely trained to operate this clinic due to their ability to perform the comprehensive risk assessments, prescribe the necessary testing and interventions, educate and collaborate with the patient on lifestyle risk modification. The longitudinal care management provided in partnership with other healthcare providers ensures that risk assessment remains dynamic and care is provided in accordance with the latest guidelines. An APP driven program successfully focuses on the individual patient, in addition to the disparate needs of the community abling the to have a positive impact on cancer outcomes by delivering truly personalized care. While many high-risk programs focus on one specific cancer type, our program will be one of the first in Wisconsin to offer a comprehensive high-risk program for multiple cancer types.

CLINICAL CASE OF COVID-19 IN A CHILD WITH A RARE SMITH-LEMLI-OPITZ SYNDROME.

Severe forms of COVID-19 are more likely to develop in children of the first year of life with genetic disorders and congenital malformations. Only a few lethal outcomes of the disease in children have been registered ongoing Worldwide over the entire period of the COVID-19 pandemic. This Article represents a clinical case of COVID-19 in a child with a rare Smith-Lemli-Opitz syndrome. On the 2nd day after the reported contact with a family member with COVID-19 the patient aged 3 years and 2 months old was hospitalized in the infectious diseases department with the diagnoses of <<Severe coronavirus infection (PCR-confirmed);cardiopulmonary insufficiency;and congenital heart disease>>. Since the age of 1.5 months old the patient repeatedly underwent inpatient examination and treatment with the Psycho-Neurological Department of the Belgorod Oblast Regional Children's Clinical Hospital (located in Belgorod, Russia). Furthermore, at the age of 1.5 y/o, according to the results of the medical genetic counseling, the diagnosis of Smith- Lemli-Opitz syndrome was established. Due to the COVID-19, the patient's condition deteriorated rapidly, and on the 5th day after the hospitalization the patient has died due to acute heart failure, cardiogenic pulmonary edema and pulmonary hemorrhage.Copyright © 2023 T.A. Kryuchkova.

Rapid Implementation of Telegenetic Counseling in the COVID-19 and Swedish Healthcare Context: A Feasibility Study.

This study reports the process and preliminary findings of rapid implementation of telegenetic counseling in the context of Swedish healthcare and COVID-19 pandemic, from both a patient and a provider perspective. Fourty-nine patients and 6 healthcare professionals were included in this feasibility study of telegenetic counseling in a regional Department of Clinical Genetics in Sweden. Telegenetic counseling is here defined as providing genetic counseling to patients by video (n = 30) or telephone (n = 19) appointments. Four specific feasibility aspects were considered: acceptability, demand, implementation, and preliminary efficacy. Several measures were used including the Genetic Counseling Outcome Scale 24 (collected pre- and post-counseling); the Telehealth Usability Questionnaire; a short study specific evaluation and Visiba Care evaluations, all collected post-counseling. The measures were analyzed with descriptive statistics and the preliminary results show a high level of acceptance and demand, from both patients and providers. Results also indicate successful initial implementation in the regional Department of Clinical Genetics and preliminary efficacy, as shown by significant clinically important improvement in patients' empowerment levels.

The TeleKidSeq pilot study: incorporating telehealth into clinical care of children from diverse backgrounds undergoing whole genome sequencing.

BACKGROUND: The COVID-19 pandemic forced healthcare institutions and many clinical research programs to adopt telehealth modalities in order to mitigate viral spread. With the expanded use of telehealth, there is the potential to increase access to genomic medicine to medically underserved populations, yet little is known about how best to communicate genomic results via telehealth while also ensuring equitable access. NYCKidSeq, a multi-institutional clinical genomics research program in New York City, launched the TeleKidSeq pilot study to assess alternative forms of genomic communication and telehealth service delivery models with families from medically underserved populations. METHODS: We aim to enroll 496 participants between 0 and 21 years old to receive clinical genome sequencing. These individuals have a neurologic, cardiovascular, and/or immunologic disease. Participants will be English- or Spanish-speaking and predominantly from underrepresented groups who receive care in the New York metropolitan area. Prior to enrollment, participants will be randomized to either genetic counseling via videoconferencing with screen-sharing or genetic counseling via videoconferencing without screen-sharing. Using surveys administered at baseline, results disclosure, and 6-months post-results disclosure, we will evaluate the impact of the use of screen-sharing on participant understanding, satisfaction, and uptake of medical recommendations, as well as the psychological and socioeconomic implications of obtaining genome sequencing. Clinical utility, cost, and diagnostic yield of genome sequencing will also be assessed. DISCUSSION: The TeleKidSeq pilot study will contribute to innovations in communicating genomic test results to diverse populations through telehealth technology. In conjunction with NYCKidSeq, this work will inform best practices for the implementation of genomic medicine in diverse, English- and Spanish-speaking populations.

An evidence-based practice guideline of the National Society of Genetic Counselors for telehealth genetic counseling.

There are currently no practice guidelines available for genetic counseling using telehealth modalities. This evidence-based practice guideline was developed in response to increasing use of alternative service delivery models for genetic counseling, specifically telephone and video-based genetic counseling (telehealth genetic counseling or THGC). A recent systematic evidence review (SER) compared outcomes of THGC with in-person genetic counseling and found that for the majority of studied outcomes, THGC was a non-inferior and comparable service delivery model. The SER results were used to develop this guideline. The current and anticipated future use of THGC, including the influence of the COVID-19 pandemic, provides the context for this guideline. Recommendation: The Telehealth Practice Guideline author workgroup conditionally recommends telehealth genetic counseling, either via telephone or video, as a delivery method for genetic counseling. Depending on factors unique to individual healthcare systems and provider and patient populations, THGC may be the only service delivery model available or may be utilized in addition to other service delivery models including in-person genetic counseling. The evidence shows large desirable effects, minor undesirable effects, and increased equity for patients when THGC is available. THGC may reduce or remove existing barriers to patient access to genetic counseling, such as medical conditions and/or disabilities that may affect a patient's ability to travel, inflexible work or school schedules, and lack of reliable transportation, finances, or dependent care. THGC is likely acceptable to key groups impacted by its use and is feasible to implement. Certain patient populations may require additional resources or encounter more barriers in using telemedicine services in general. For these populations, THGC can still be a valuable option if solutions are available.

A digital pathway for genetic testing in UK NHS patients with cancer: BRCA-DIRECT randomised study internal pilot.

BACKGROUND: Germline genetic testing affords multiple opportunities for women with breast cancer, however, current UK NHS models for delivery of germline genetic testing are clinician-intensive and only a minority of breast cancer cases access testing. METHODS: We designed a rapid, digital pathway, supported by a genetics specialist hotline, for delivery of germline testing of BRCA1/BRCA2/PALB2 (BRCA-testing), integrated into routine UK NHS breast cancer care. We piloted the pathway, as part of the larger BRCA-DIRECT study, in 130 unselected patients with breast cancer and gathered preliminary data from a randomised comparison of delivery of pretest information digitally (fully digital pathway) or via telephone consultation with a genetics professional (partially digital pathway). RESULTS: Uptake of genetic testing was 98.4%, with good satisfaction reported for both the fully and partially digital pathways. Similar outcomes were observed in both arms regarding patient knowledge score and anxiety, with <5% of patients contacting the genetics specialist hotline. All progression criteria established for continuation of the study were met. CONCLUSION: Pilot data indicate preliminary demonstration of feasibility and acceptability of a fully digital pathway for BRCA-testing and support proceeding to a full powered study for evaluation of non-inferiority of the fully digital pathway, detailed quantitative assessment of outcomes and operational economic analyses. TRIAL REGISTRATION NUMBER: ISRCTN87845055.

Using telemedicine in a cystic fibrosis newborn screening clinic

Background: Most patients are diagnosed with cystic fibrosis (CF) based on newborn screening (NBS). The goal of CF NBS is to achieve early CF diagnosis to start medical and psychosocial therapies before the onset of clinical symptoms to improve disease outcomes. Thus, infants require diagnostic testing before 4 weeks of age. With the onset of the COVID-19 pandemic and shut-down of nonurgent medical services from March to May 2020, many health care systems transitioned from traditional, inperson clinical visits to a telemedicine platform. We outline our institutional review board-exempt, quality-improvement efforts to transition to a CF NBS clinic that occurs primarily via telemedicine at our CFFaccredited pediatric center in Delaware. Method(s): The medical records of infants with inconclusive CF NBS referred to our clinic were reviewed from May 2020 to December 2021 once telemedicine visits were offered. Demographic information including date of birth, age completing NBS, age at referral for diagnostic sweat chloride testing (ST), number of family contacts to schedule ST, age at successful ST completion, and format for subsequent discussion of results via telemedicine or alternate mode plus date was reviewed. Charts of infants referred from Delaware and surrounding states were also reviewed to assess ST success rates and need for additional testing, genetic counseling consultation, or in-person CF clinic visits. Result(s): One hundred eighty-seven infants (68 between May 2020 and December 2020, 119 in 2021) were referred. Average age at completion of CF NBS was 1.4 days (range 1-8 days) in 2020 and 1.78 days (range 1-14 days) in 2021. Average age at referral for diagnostic testing was 10.7 days (range 1-78 days) in 2020 and 10.3 days (range 0-150 days) in 2021 in Delaware. Forty-eight of 52 (92%) Delaware families were contacted to schedule diagnostic testing before 21 days of age in 2020 and 88 of 94 (94%) in 2021. The CF NBS clinic made an average of 1 contact (range 1-5) with each family to schedule testing and appointments in 2020 and 2 (range 1- 10) in 2021. The overall ST success rate from May 2020 to December 2021 was 87% (n = 189/217 ST completed). Diagnostic test results were relayed via telemedicine to 92 patients, telephone to 61 patients, in person to 21 patients, by primary care provider to five patients, and not specified in eight patients. Genetic counseling was completed for nine families based on CF NBS results. Over the period, four infantswere diagnosed with CF-all had in-person clinic visits on average at age 11 days (range 9 to 21 days). A diagnosis of CF transmembrane conductance regulator-related metabolic syndrome (CRMS)was noted in three infants who had in-person visits at an average age of 20 days (range 16-21 days);two required rescheduling from telemedicine to in-person assessment within 24 to 72 hours of initial time based on intermediate ST results. Conclusion(s): Telemedicine visits offer an alternate way to communicate diagnostic ST results to families of infants with inconclusive CF NBS. Infants identified with CF and CRMS were scheduled for a traditional clinic visit or required rapid follow-up scheduling for an in-person evaluation. A need for better communication between CF NBS clinic staff and families to schedule and complete testing was noted. Future directions include assessing optimal ways to contact families and reminders for ST and clinical appointments Copyright © 2022, European Cystic Fibrosis Society. All rights reserved

The Cancer and Research Center of Marche Region (Corm): A New Instrument to Offer Opportunities for Diagnosis and Treatment to Cancer Patients

Following the new health needs emerged during the covid pandemic, in June 2021, the Cancer and Research Center of Marches Region, CORM (www.corm-marche.it) was instituted at the Department of Oncology of the Academic Hospital Ospedali Riuniti, Ancona (IT) with the Italian Ministry of Health patronage. The CORM includes:-The digital platform for telemedicine to offer the ability to admit de novo diagnosis of solid tumors, as well as provide second opinions and to promote continutiy of care between hospital and territory-The Molecular Tumor Board, a multidisciplinary board including clinicians, pathologists and biologists to recommend personalized therapy in the "Precision Medicine" era. High throughput genomic profiling tests may be indicated by MTB team: foundation one cdx/liquid biopsy/ heme, 16 genes DNA panel and other panels that are relevant in different types of tumors, NTRK evaluation and PDL1 test. The molecular profiles are useful to indicate new treatment strategies, but also to understand the mechanism of resistance otherwise not justificable with a standard approach.-The Clinical Trial Unit which performs about 40 interventional trials/year and includes a phase 1 unit, certified by AIFA. Every year, 100 patients are enrolled in clinical trials, about 10/year in phase 1 trials.-The Regional Center of High Specialization in Oncological Genetics. In December 2004, the Regional Center of High Specialization in Oncological Genetics was instituted and we developed an increasing expertise in genetic counseling and tests for hereditary syndrome (hereditary breast and ovarian cancer syndrome and Lynch syndrome). Last year, we conducted 3166 genetic counseling, consisting of collecting genetic information and drawing pedigree, making or validating diagnosis, communicating clinical and genetic information and supporting the family to reach a decision and take appropriate actions. From January 2022, we activate the telemedicine platform also for genetic counseling to select patients who deserve genetic testing and come from distant territories. We aim to create a technological network between the oncology departments and general practitioners, patient associations and all the other specialists to guarantee the continuity of care and to overcome the disparities in oncological health services, simplifying cancer clinical management.

Hereditary Breast and Ovarian Cancer Service in Sparsely Populated Western Pomerania.

The German Consortium Hereditary Breast and Ovarian Cancer (GC-HBOC) consists of 23 academic centers striving to provide high-quality regional care for affected individuals and healthy at-risk family members. According to the standard operating procedures defined by the GC-HBOC, a Familial Breast and Ovarian Cancer Center was implemented at the University Medicine Greifswald over a four-year period from 2018 to 2021, despite the COVID-19 pandemic. Genetic analyses were performed in a total of 658 individuals, including 41 males, which paved the way to local annual risk-adapted breast cancer surveillance for 91 women and prophylactic surgery for 34 women in 2021. Our experience in the North Eastern part of Germany demonstrates that it is possible to establish a high-risk breast and ovarian cancer service even in a sparsely populated region. Major facilitators are the interdisciplinary collaboration of dedicated local experts, the support of the GC-HBOC, fruitful clinical and scientific cooperations and the use of technical improvements. As a blueprint, our project report may help to further expand the network of specialized and knowledge-generating care for HBOC families.

Telemedicine for Hd during the Covid-19 Pandemic: Results of a European Survey

Video consultations have become a viable alternative for face-to-face consultations during Covid19 pandemic and are expected to be used increasingly in the future. To date, there is little evidence to support the acceptability of these services or to document the benefits and challenges when offering online clinics to HD patients. Method We report on an EHDN WG Genetic Counselling and Testing project of 41 healthcare professionals from 15 European countries. Participants filled in a purposely-designed survey to assess the acceptability, benefits and challenges of telemedicine with HD affected and at risk individuals. The survey was active from March 2020 until March 2021. Results Respondents were geneticists (34%), neurologists (34%), genetic counsellors (15%), and others (psychologists, psychiatrists and research practitioners) (17%). Before the Covid-19 pandemic, professionals saw 4.5 HD patients per week and most (85%) never used telemedicine. During the pandemic, professionals saw 2.4 patients per week in face-toface consultations and 3.4 patients in online consultations. 85% of professionals felt that HD clinics can be done safely and effectively online. Most respondents agreed several aspects of consultations can be done safely online: follow-up counselling (78%), genetic counselling for predictive testing (54%), psychological assessment (49%), psychiatric and behavioural assessment (44%). The main benefits of telemedicine perceived were and challenges were also listed and discussed at length. Conclusions and discussion Our data are encouraging in relation to the potential for virtual and hybrid consultations in HD care. We draw on both quantitative and qualitative data to discuss professionals' views on telemedicine as well as potential implications for future practice.

Health information technology to improve referral to genetic testing for high-risk patients in a gynecologic oncology clinic (102)

Objectives: Our previously presented pilot study evaluated a web-based tool to collect family cancer history (FCH). It demonstrated that this tool resulted in significantly higher quality FCH compared to standard of care face-to-face physician interviews. However, the true value of FCH requires translation into the utilization of genetic services. Here, we aimed to evaluate referral rates and completion of genetic services for patients completing the web-based tool versus standard of care. Methods: Patients scheduled for a gynecologic oncology new patient visit between September 2019 and September 2021 were eligible for enrollment in this institutional review board-approved prospective trial. The trial had three arms: 1) Standard of care (FCH collection by physicians) 2) Web-based tool administered by email prior to the visit, 3) Web-based tool administered in the office prior to the visit (this arm closed early due to COVID-19 restrictions). Individuals were identified as high-risk for familial cancer if they met National Comprehensive Cancer Network (NCCN) guidelines in the standard of care arm, or if the validated cancer risk models embedded in the web-based tool returned a lifetime cancer risk >20% or mutation risk?>2.5% in the web-based tool arms. Validated risk assessment models included breast and ovarian BRCAPRO, Claus, Tyrer-Cuzick, Gail, colorectal and endometrial MMRPRO, MELAPRO, PANCPRO, and PREMM. The primary endpoint was the percentage of high-risk patients referred for genetic counseling/testing. Secondary endpoints included the completion of genetic counseling and genetic testing. Results: Two hundred and fifty patients were enrolled (Arm 1: 110;Arm 2: 105;Arm 3: 35). Among patients randomized to the web-based tool, 88 (63%) completed the tool. In the control arm, 31 patients (28%) met the criteria for referral to genetics, among which 18 (58%) had previously completed genetic testing. In the web-based tool arm, 26 patients (30%) met the criteria, among which 12 (46%) had previously completed genetic testing, and one was deceased soon after her visit. In the control arm, 54% of high-risk patients were referred to genetic counseling, 23% completed genetic counseling, and 23% completed genetic testing. In the web-based tool arm, 100% of high-risk patients were referred to genetic counseling, 54% completed genetic counseling, and 38% completed genetic testing (Table 1). Conclusions: When successfully completed, the use of a web-based tool for FCH collection facilitated the process of referral to genetics, resulting in significantly higher referral rates to genetic counseling than the standard of care physician interviews (100% vs 54%, p = 0.01). However, 37% of patients could not complete the web-based tool. Our findings demonstrate the potential power of health information technology to identify millions of individuals unknowingly carrying familial cancer syndromes and highlight those tools must be designed in a way to maximize patient participation.[Formula presented]

Telegenetics and COVID 19: Through the Pandemic and Beyond

Introduction - The COVID 19 pandemic led to restrictions on the conventional ways of healthcare delivery. Telemedicine provided a viable solution that was in line with the social distancing policies imposed to minimize disease transmission. This demanded physicians adapt to new ways of healthcare delivery. We surveyed geneticists across the country to determine their experience and to ascertain if telegenetics will be a lasting change. Materials and Methods - A 23 item standardized survey was distributed to various US-based geneticists via email and other social media platforms focusing on their experience of providing care via telemedicine. Results - We received 69 responses from physicians across 26 states. Of these, 91% practiced in academia. 70% responded that pediatric genetics takes up more than 50% of their practice. 68% had over 50% of their practice switch to telemedicine. 77% felt they could provide adequate care via telemedicine and 94% of providers would like to continue telemedicine post-pandemic. Conclusion - The future of telemedicine looks promising as the majority of clinicians would like to routinely use telemedicine post-pandemic. Uniform guidelines for use of telemedicine in genetics may need to be proposed by professional societies and supported by federal laws.