High-risk Family Members Research Articles

Социальная помощь семьям группы риска: практика реализации проекта «Обучение служением»

Interaction with high-risk families and providing social assistance to children from these families are among the priority issues considered within the framework of implementing Russian state social policy. The modern period of development of this industry is characterized by the active inclusion of volunteer practices in the process of socialization and prevention of deviant behavior among members of high-risk families, including through the formation of their subjectivity. One of the examples of volunteer practices analyzed in the study is the Ministry Training Project. By the method of content analysis, current social orders implemented within the framework of the project under study were systematized and described as one of the directions for interaction with families of the risk group and children from these families. The results of the study demonstrate differences in the degree of prevalence of Ministry Training Project practices in relation to at-risk families. The implementation of the project’s social orders is extended to only one category of this group – families raising disabled children and children with disabilities, while other categories (social orphans, antisocial families, single-parent families, etc.) are not represented within the framework of the project.

The Significance of Screening Family Members in Glaucoma: Opportunities and Challenges.

This article delves into the imperative of screening family members of patients with glaucoma due to the disease's hereditary nature. It discusses the significant risks faced by first-degree relatives, approaches for identification, and challenges in implementing effective screening strategies. Emphasizing education, targeted campaigns, community involvement, and collaborative healthcare approaches, the article highlights the potential for mitigating undiagnosed glaucoma cases through strategic interventions targeting high-risk individuals. This article underscores the importance of screening family members of glaucoma patients, emphasizing the hereditary nature of the disease and the potential for screening to allow for early intervention to help prevent unnecessary vision loss. Glaucoma, affecting over 111.8 million by 2040, is relatively asymptomatic until late in the disease. Genetics predispose to glaucoma, with up to 70% heritability. High-risk individuals, particularly first-degree relatives, exhibit substantially elevated glaucoma risks-up to 22% compared with 2.3% in controls. Family history also correlates with greater disease severity. Identifying high-risk family members through cascade screenings for causative genes or direct examinations during proband visits emerges as efficient strategies. Challenges persist, including slow progression, healthcare accessibility, and ethical dilemmas in implementing family member screening. Challenges extend to the healthcare system, socioeconomic barriers, and familial communication issues. Efforts to educate probands and the public on the hereditary nature of glaucoma are pivotal. Tailored education campaigns, leveraging clinic visits, and community screenings, complemented by optometrist collaboration, form essential strategies. Although challenges hinder family member screening, educating probands, targeted patient education, collaborative healthcare approaches, and community involvement offer promising avenues to combat undiagnosed glaucoma cases.

A cost-utility analysis of BRCA1 and BRCA2 testing in high-risk breast cancer patients and family members in Thailand: a cost-effective policy in resource-limited settings.

Screening for germline pathogenic BRCA1 or BRCA2 variants (gBRCA) in high-risk breast cancer patients is known to be cost-effective in high-income countries. Nationwide adoption of genetics testing in high-risk breast cancer population remains poor. Our study aimed to assess gBRCA health economics data in the middle-income country setting of Thailand. Decision tree and Markov model were utilized to assess cost-utility between the testing vs. no-testing groups from a societal and lifetime perspective and lifetime. We interviewed 264 patients with breast/ovarian cancer and their family members to assess relevant costs and quality of life using EQ-5D-5L. One-way sensitivity, probabilistic sensitivity (Monte Carlo simulation), and budget impact analyses were done to estimate the outcome under Thailand's Universal Health Coverage scheme. The predicted lifetime cost and Quality-adjusted Life Years (QALY) for those with breast cancer were $13,788 and 10.22 in the testing group and $13,702 and 10.07 in the no-testing group. The incremental cost-effectiveness ratio for gBRCA testing in high-risk breast cancer patients was $573/QALY. The lifetime cost for the family members of those with gBRCA was $14,035 (QALY 9.99), while the no-testing family members group was $14,077 (QALY 9.98). Performing gBRCA testing in family members was cost-saving. Cost-utility analysis demonstrated a cost-effective result of gBRCA testing in high-risk breast cancer patients and cost-saving in familial cascade testing. The result was endorsed in the national health benefits package in 2022. Other middle-income countries may observe the cost-effective/cost-saving aspects in common genetic diseases under their national health schemes.

Evaluation of Family and Community Social Network Characteristics Among High-Risk Family Members to Improve Cancer-Related Health Behaviors.

To evaluate the effects of social network characteristics of individuals with a family history of cancer on the use of cancer-related services (e.g., screening, genetic counseling/testing). 170 family members of individuals with the most common hereditary or familial cancers. Data collection occurred between March and September 2021 using an online survey. Having strong within-immediate family relationships and family members who underwent more screening procedures was associated with increased breast cancer screening, and having more family members with cancer was associated with colorectal cancer screening. Having a large family, having family members who underwent screening for more cancers, and having strong social cohesion among families were associated with an increased rate of genetic testing. Nurses working with families affected by cancer should focus on strategies to strengthen relationships among family members to improve knowledge of cancer screening and available genetic services.

Prevalence and genetic spectrum associated with hereditary colorectal cancer syndromes, the need to improve cancer risk awareness, and family cascade testing in Vietnam.

In Vietnam, colorectal cancer is one of the top diagnosed cancers, with 5-10% originating from inherited mutations. This study aims to define the mutation spectrum associated with hereditary colorectal cancer syndromes (HCCS) in Vietnam, evaluate the influence of genetic testing on carriers' awareness, and also investigate the barriers in familial testing. Genetic test reports were collected to identify HCCS cases, then cases underwent a survey investigating self-risk and familial-risk awareness, proactive cancer screening, and familial testing barriers. Participant characteristics, mutation prevalence, and results from the survey were descriptively analyzed and reported. Of all genetic test results, 3% (49/1632) were identified with mutations related to HCCS. Over 77% of them belonged to Lynch syndrome. PMS2 appeared to be the gene with the highest mutation frequency, while MLH1 was the lowest. 44% of cases further undertook cancer screening tests, and 48% of cases' families had uptake genetic testing. The biggest barrier of familial members for not taking genetic test was psychological reasons (fear, not being interested, or not feeling necessary). This study provided new evidence for HCCS mutation spectrum in Vietnamese population and the success in promoting cascade test in high-risk family members through financial and technical support. Also, study has suggested the needs of an innovative genetic testing process focusing on the quality of pre-and post-test consultancy, an increase in follow-ups, and the change in policy for permission of contacting relatives directly to improve the rate of cascade testing and proactive cancer screening.

Atypical Face Process in Autism Spectrum Disorder and Relevant Interventions

The current study overviewed previous research on abnormalities in face processing in individuals with autism spectrum disorder (ASD) and concluded implications on development of relevant social skill interventions. Overall, autistic individuals exhibited deviated neural activity patterns during face processing across different ages, suggesting that atypical development of neural structures might be accountable for deficits in social functioning. Similarly, familial studies found no significant variations in neural activity patterns for high-risk family members, providing insufficient evidence for the inheritance of autism. Although neural activity indices might not be effective as biomarkers for early life diagnosis, researchers could use these indicators to predict the extent of social impairment for patients in later life stages. Social functioning programs based on facial processing schemes had a significant training effect on young patients, but further testing trials are required to estimate their impact on patients social behaviors in real life. This review can provide some guidance for the design of intervention programs at schools for children with ASD.

Genome sequencing identifies complex structural MLH1 variant in unsolved Lynch syndrome.

Lynch syndrome is one of the most common cancer predisposition syndromes. It is caused by inherited changes in the mismatch repair pathway. With current diagnostic approaches, a causative genetic variant can be found in less than 50% of cases. A correct diagnosis is important for ensuring that an appropriate surveillance program is used and that additional high-risk family members are identified. We used clinical genome sequencing on DNA from blood and subsequent transcriptome sequencing for confirmation. Data were analyzed using the megSAP pipeline and classified according to basic criteria in diagnostic laboratories. Segregation analyses in family members were conducted via breakpoint PCR. We present a family with the clinical diagnosis of Lynch syndrome in which standard diagnostic tests, such as panel or exome sequencing, were unable to detect the underlying genetic variant. Genome sequencing in the index patient confirmed the previous diagnostic results and identified an additional complex rearrangement with intronic breakpoints involving MLH1 and its neighboring gene LRRFIP2. The previously undetected structural variant was classified as medically relevant. Segregation analysis in the family identified additional at-risk individuals which were offered intensified cancer screening. This case illustrates the advantages of clinical genome sequencing in detecting structural variants compared with current diagnostic approaches. Although structural variants are rare in Lynch syndrome families, they seem to be underreported, in part because of technical challenges. Clinical genome sequencing offers a comprehensive genetic characterization detecting a wide range of genetic variants.

Study of myocillin gene variants alleles in primary open angle glaucoma patients and their first degree relatives in North West Rajasthan, India

Glaucoma is defined as progressive optic neuropathy leading to irreversible blindness if not treated on time. Primary open angle glaucoma (POAG) is most common form of glaucoma. Mutations in myocilin gene (MYOC) account for 2–4% of POAG cases. To identify and evaluate MYOC variants alleles among patients with POAG and their healthy first degree relatives. 66 POAG patients and 26 healthy first degree relatives recruited for study. All patients underwent complete ophthalmic examination followed by genomic DNA (deoxyribonucleic acid) isolation from peripheral blood and quantification of DNA on spectrophotometer. All samples were amplified with each primer by PCR (Polymerase Chain Reaction) technique and amplified DNA and primer sequence checked again by electrophoresis for confirmation of specified MYOC gene mutation. We identified a known MYOC missense mutation, Pro370leu in 16 POAG cases and found consistent genotypic but not phenotypic correlation in 4 of their first degree relatives. Out of 16 cases, pathogenic MYOC gene variant was found in 12 adult onset POAG, 3 juvenile onset POAG, and 1 case of OHT. This study is first of its kind in North India. Our study showed frequency of MYOC gene mutation in POAG cases was 24.24% which is much higher than found elsewhere in India and other countries (2-5%). Frequency of transmission of pathogenic MYOC gene variant in first degree relatives was 25%. The future outcome of our study is promising since early diagnosis and management of high risk family members is possible.

Mapping T Cell Responses to Native and Neo-Islet Antigen Epitopes in at Risk and Type 1 Diabetes Subjects.

AimsRecent studies highlight the potentially important role of neoepitopes in breaking immune tolerance in type 1 diabetes. T cell reactivity to these neoepitopes has been reported, but how this response compares quantitatively and phenotypically with previous reports on native epitopes is not known. Thus, an understanding of the relationship between native and neoepitopes and their role as tolerance breakers or disease drivers in type 1 diabetes is required. We set out to compare T cell reactivity and phenotype against a panel of neo- and native islet autoantigenic epitopes to examine how this relates to stages of type 1 diabetes development.MethodsFifty-four subjects comprising patients with T1D, and autoantibody-positive unaffected family members were tested against a panel of neo- and native epitopes by ELISPOT (IFN-γ, IL-10, and IL-17). A further subset of two patients was analyzed by Single Cell Immune Profiling (RNAseq and TCR α/β) after stimulation with pools of native and neoepitope peptides.ResultsT cell responses to native and neoepitopes were present in patients with type 1 diabetes and at-risk subjects, and overall, there were no significant differences in the frequency, magnitude, or phenotype between the two sets of peptide stimuli. Single cell RNAseq on responder T cells revealed a similar profile in T1D patients stimulated with either neo- or native epitopes. A pro-inflammatory gene expression profile (TNF-α, IFN-γ) was dominant in both native and neoepitope stimulated T cells. TCRs with identical clonotypes were found in T cell responding to both native and neoepitopes.Conclusion/InterpretationThese data suggest that in peripheral blood, T cell responses to both native and neoepitopes are similar in terms of frequency and phenotype in patients with type 1 diabetes and high-risk unaffected family members. Furthermore, using a combination of transcriptomic and clonotypic analyses, albeit using a limited panel of peptides, we show that neoepitopes are comparable to native epitopes currently in use for immune-monitoring studies.

Cascade screening for glaucoma in high-risk family members of African-Caribbean glaucoma patients in an urban population in London

Background/aimsCascade screening has been used successfully in relatives of patients with inherited cancers and other genetic diseases to identify presymptomatic disease. This study was designed to examine if this approach...

Characterization of Rare Germline Variants in Familial Multiple Myeloma

Introduction: The risk of developing Multiple Myeloma (MM) is 2-4 fold higher in first-degree relatives of patients with MM compared to the general population, suggesting genetic predisposition to this cancer. Indeed, recent genome-wide association studies have identified common risk alleles that predispose for MM. Yet, the impact of these variants on MM risk is too low to explain familial aggregation of MM. High-impact alleles have been identified for other cancers such as ovarian and breast cancer (BRCA1,-2) and melanoma (CDKN2A) but the search for such alleles in MM is still in its infancy. In order to identify high-impact alleles in MM we have performed whole genome/exon sequencing (WGS/WES) in members of MM high risk families. Methods: We included 21 families with multiple cases of MM/MGUS. Whole genome/exome sequencing was performed on a total of 46 affected and 20 unaffected family members. Filtering and prioritization of the variants were performed in accordance with the criteria of our in-house familial cancer variant prioritization pipeline version 2 (FCVPPv2). Loss-of-function variants were further screened using MutPred-LOF, Translate tool and IntOGen/c-BioPortal in order to discriminate pathogenic and neutral variants, to translate a nucleotide sequence to a protein sequence and to visualize the domain affected by the variant and the portion of the protein lost after the newly formed stop codon. Variants were analyzed for predicted effects on splicing by using Human Splicing Finder. Results: We found a total of 148 potentially pathogenic variants, 109 non-synonymous and 39 LOF, in 18 out of 21 MM families. Among our genes, many affect protein metabolism, immune system, and other have known links to carcinogenesis. Additionally, some of them are known to interact with key signaling pathways in MM, including PI3K/Akt/mTOR, Ras/Raf/MEK/MAPK, JAK/STAT, NF-κB, Wnt/β-catenin, and RANK/RANKL/OPG, showing congruency with previously reported literature. Interestingly, we also found different missense variants in the same two genes in two unrelated families. Conclusions: We have identified potentially pathogenic gene variants in 85% of MM/MGUS families. Our results can offer a useful reference to gene finding efforts by others in order to improve screening, early diagnosis and personalized therapy of individuals at risk of developing MM. Disclosures Durie: Amgen, Celgene, Johnson & Johnson, and Takeda: Consultancy. Goldschmidt:Merck Sharp and Dohme (MSD): Research Funding; Molecular Partners: Research Funding; Incyte: Research Funding; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding; Johns Hopkins University: Other: Grants and/or provision of Investigational Medicinal Product; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Grants and/or provision of Investigational Medicinal Product:, Research Funding; Dietmar-Hopp-Foundation: Other: Grants and/or provision of Investigational Medicinal Product:; Chugai: Honoraria, Other: Grants and/or provision of Investigational Medicinal Product:, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Grants and/or provision of Investigational Medicinal Product:, Research Funding; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Grants and/or provision of Investigational Medicinal Product:, Research Funding; University Hospital Heidelberg, Internal Medicine V and National Center for Tumor Diseases (NCT), Heidelberg, Germany: Current Employment; GlaxoSmithKline (GSK): Honoraria; Adaptive Biotechnology: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Grants and/or provision of Investigational Medicinal Product, Research Funding; Novartis: Honoraria, Research Funding; Mundipharma GmbH: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding.

8 Emergency Physician COVID-19 Readiness and Practices

The purpose of this survey study was to assess the working environment of emergency physicians (EPs) early in the Corona Virus Disease 2019 (COVID-19) pandemic. Areas of interest included access to appropriate personal protective equipment (PPE), hospital policy, personal effects of the pandemic on EPs, and how the pandemic has changed their individual practices. An anonymous Survey Monkey survey for all practicing EPs was released on an EPs social medial group in mid-April 2020. The survey consisted of 15 questions covering demographics, hospital policies and work environment, individual physician concerns and changes in practice and habits. 220 emergency physicians responded to the survey with 209 complete submissions. 41 of 50 states, Puerto Rico, and Canada had at least one response. Almost one-third have been in practice for either 5-9 years and 10-19 years post-residency each. More than half work in a community hospital (58%) and approximately one-third work at a tertiary or regional medical center. There was a wide spread in the number of ICU beds at their facility on a scale of 0-50 in increments of 10. Although the vast majority report isolated COVID-19 areas and limited visitors, nearly 15% reported that their site did not have any current plans to create an isolated area. About half reported a hospital policy requiring N95 respirators in COVID-19 positive or suspected rooms although a quarter of those also included wearing N95 respirators in all patient rooms (N95s). Other common policies included universal masking and N95s for high risk or aerosolizing procedures only. N95s and surgical masks were the most commonly provided PPE. 86% were concerned about short term shortages or were already facing shortages. More than half reported access to a powered air-purifying respirator (PAPR). N95s were the most likely to run out (82%) followed by gowns (60%) and surgical masks (42%). Most purchased at least one item of PPE (86%). Three-quarters report not self-quarantining at home, although almost all (98%) have added steps to reduce risk of bringing contaminants home. Removing shoes and work clothes prior to entering the home (86%) and immediately showering upon arriving home (88%) were the most common practices followed by showering and/or changing at the hospital (45%). Other responses included cleaning or separating personal work items, temporarily living in a separate location, or limiting contact with others in the household. The majority were concerned about transmitting COVID-19 to low and/or high-risk friends or family members (74% and 72%, respectively). Almost one-quarter were high risk and were concerned about becoming ill. More than half were concerned about the personal financial impact of the pandemic. One month after COVID-19 was declared a pandemic by the World Health Organization and a national emergency by the United States we surveyed emergency physicians, COVID-related policy changes, supply chains, and personal effects. At that time most hospitals had enacted policies regarding PPE use, created isolated COVID areas, and limited visitors. Most EPs had concerns regarding immediate and short-term inadequate PPE supplies and have bought at least one PPE item to use at work. Very few emergency physicians reported no concerns regarding personal risks of contracting or transmitting COVID.

Effect of Nursing Terapeutic Communication (Spiritual Approach) Onperception, Cortisol and HSP70 Family Members with High Risk of TB Infection

Tuberculosis is an infectious disease. Preventive efforts are needed, so that, the members of a familywho live under one roof (high risk family members) of tuberculosis patients are not easily infected by thedisease. Family is involved only as a drug consumption controller. So far, there has been no effort to maintainand improve the health of high risk family members. The objective of this study was to elaborate the effect ofnursing therapeutic communication on perception, cortisol and HSP70 of pulmonary tuberculosis high riskfamily members. A pre-experimental study was conducted using one group pre-test and post-test design.Samples obtained were 20 respondents using random sampling. The independent variable in this study wastherapeutic communication (dimension of knowledge on transmission prevention and spiritual) while thedependent variable were perception (knowledge and spiritual dimensions), cortisol and HSP70. Data werecollected using questionnaire and observation sheet and were tested using paired t-test. After the therapeuticcommunication, there was an improvement in perception (p = 0.000), cortisol reduction (p = 0.0005) andincrease of HSP70 (p = 0.004). There was significant difference in perception, cortisol level and HSP70 levelbefore and after therapeutic communication. Therapeutic communication was able to improve the respondent’sperception and the immunity of tuberculosis high risk family members. Recommendations to prevent TBtransmission in Public Health Center of Wonokromo were; Undergoing therapeutic communication (knowledgeon transmission prevention and spiritual in TB high risk family members, so that, their immunity will improveand become not easily being infected and providing training to the nurses in order to improve the elements oftherapeutic communication capability.

Evaluation of Genetic Counselling in Patients With High Adenoma Burden

Introduction: Up to 10% of cancers are caused by inherited mutations in genes. Identifying these patients is important as it leads to changes in the surveillance of the index patient and their the family and plays a very important role in further management of these patients. While genetic counselling/testing allow for identification of high-risk individuals and family members enabling enrollment into appropriate screening protocols. Currently, GI guidelines and the National Comprehensive Cancer Network guidelines suggest referral of individuals with ≥10 adenomatous polyps for evaluation and consideration of genetic testing. The goal of this study is to determine the efficacy of execution of genetic counselling at a teaching hospital. Methods: This study was an IRB approved retrospective review performed at a tertiary referral VA center in Tampa, Florida. We reviewed 11540 patients who underwent screening or surveillance colonoscopy and included patients who procedures noted more than 10 polyps<./p> Results: A total of 61 veterans (mean age 71 years old, 58 males and 3 females) met inclusion criteria for the study. The cohort included 54 Caucasian, 2 Hispanic and 3 African American patients. 52 patients were found to have >10 biopsy proven adenomas, the remaining patients with hyperplastic polyps. 1 patient underwent documented genetic counselling, and 4 patients underwent genetic testing; 7 patients were lost to follow-up. In patient's that did undergo genetic testing, APC was performed in 2 patients and 1 patient underwent MSI and IHC testing each. The importance of genetic intervention is reinforced as 5%(9/61) patients included in our study had a positive family history of colon cancer increasing their predisposition to develop genetic cancer syndromes. Despite follow up, 76% (40/52) patients did not undergo further evaluation. Conclusion: Current GI guidelines recommend genetic testing to confirm a diagnosis and allow for predictive testing of at-risk relatives. This study demonstrates the low overall referral rate for genetic counselling and testing in our academic center. We suspect that this low referral rate is consistent with current community practice. The causes for low genetic testing and counselling may be multifactorial such as patient compliance, poor communication with patients, and fear of testing. Further initiatives such as an automated genetic referral with detection of multiple adenomas may improve future outcomes and increase compliance with current guidelines.

Assessment of Early Evidence of Multiple Sclerosis in a Prospective Study of Asymptomatic High-Risk Family Members

Subclinical inflammatory demyelination and neurodegeneration often precede symptom onset in multiple sclerosis (MS). To investigate the prevalence of brain magnetic resonance imaging (MRI) and subclinical abnormalities among asymptomatic individuals at risk for MS. The Genes and Environment in Multiple Sclerosis (GEMS) project is a prospective cohort study of first-degree relatives of people with MS. Each participant's risk for MS was assessed using a weighted score (Genetic and Environmental Risk Score for Multiple Sclerosis Susceptibility [GERSMS]) comprising an individual's genetic burden and environmental exposures. The study dates were August 2012 to July 2015. Participants in the top and bottom 10% of the risk distribution underwent standard and quantitative neurological examination, including disability status, visual, cognitive, motor, and sensory testing, as well as qualitative and quantitative neuroimaging with 3-T brain MRI and optical coherence tomography. This study included 100 participants at risk for MS, with 41 at higher risk (40 women [98%]) and 59 at lower risk (25 women [42%]), at a mean (SD) age of 35.1 (8.7) years. Given the unequal sex distribution between the 2 groups, the analyses were restricted to women (n = 65). When considering all measured outcomes, higher-risk women differed from lower-risk women (P = .01 by omnibus test). Detailed testing with a vibration sensitivity testing device in a subgroup of 47 women showed that higher-risk women exhibited significantly poorer vibration perception in the distal lower extremities (P = .008, adjusting for age, height, and testing date). Furthermore, 5 of 65 women (8%) (4 at higher risk and 1 at lower risk) met the primary neuroimaging outcome of having T2-weighted hyperintense brain lesions consistent with the 2010 McDonald MRI criteria for dissemination in space. A subset of participants harbor many different neuroimaging features associated with MS, including perivenous T2-weighted hyperintense lesions and focal leptomeningeal enhancement, consistent with the hypothesis that these individuals are at higher risk of developing clinical symptoms of MS than the general population. Higher-risk asymptomatic family members of patients with MS are more likely to have early subclinical manifestations of MS. These findings underscore the importance of early detection in high-risk individuals. clinicaltrials.gov Identifier: NCT01353547.

Factors associated with vaccination status among Korean submariners who are eligible for free non-mandatory influenza vaccination

IntroductionSubmarine crews live in a confined setting and are vulnerable to influenza. Thus, it would be useful to identify factors that are associated with influenza vaccination. In this study, we investigated the influenza vaccination rate and the influence of health beliefs on the vaccination rate among submariners who were eligible for a free but non-mandatory vaccination program. MethodsA total of 487 Korean submariners participated in this study after the closing of a free influenza vaccination program in 2015. Data regarding the participants’ general characteristics and health beliefs (based on the health belief model [HBM]) were collected using a self-administered questionnaire, and their vaccination status was determined using their medical records. Multiple logistic regression analysis were performed to evaluate the associations of the HBM components with influenza vaccination. ResultsThe overall vaccination rate was 78% (921/1183). The unvaccinated and vaccinated respondents exhibited similar characteristics, although the vaccinated group was significantly more likely to have high-risk family members (chronic disease, age of <2years, or age of ⩾65years; p=0.025). Among the HBM components, perceived severity (odds ratio: 1.38, p=0.019) and cue to action (odds ratio: 1.74, p=0.002) were significantly associated with a higher likelihood of influenza vaccination. ConclusionVaccination policies that emphasize the severity of influenza and prompt individuals to undergo vaccination are needed to increase the vaccination rate among people who live in confined environments or institutions with non-mandatory vaccination programs.

The Role of Epstein-Barr Virus DNA Load and Serology as Screening Tools for Nasopharyngeal Carcinoma.

Screening for nasopharyngeal carcinoma (NPC) among family members has been advocated in endemic populations in view of significantly increased risks. We aimed to compare the role of Epstein-Barr virus (EBV) DNA load and EBV IgA serology as tools for screening patients with a first-degree family history of NPC. Case-control study. Tertiary referral center. Serum samples were compared from 293 newly diagnosed NPC patients and 475 individuals with a first-degree family history of NPC. EBV DNA load was measured by real-time quantitative polymerase chain reaction, while EBV viral capsid antigen (VCA) IgA and EBV early antigen (EA) IgA titers were measured by immunofluorescence assays. NPC patients had a significantly higher median EBV DNA load as compared with unaffected family members (835.4 vs 18.8 copies/mL; P < .001). At 100 copies/mL, EBV DNA load demonstrated a sensitivity of 76.8% and a specificity of 85.6%. A positive EBV-EA IgA titer (≥1:10) gave a sensitivity of 85.0% and a specificity of 96.4%. There was good correlation between EBV DNA load and EBV serology titers (Spearman's ρ = .536 and .594 for EBV-VCA IgA and EBV-EA IgA, respectively; P < .001). Receiver operating characteristic analysis demonstrated that EBV-VCA IgA and EBV-EA IgA were better classifiers than EBV DNA load (areas under the curve: 0.942, 0.926, and 0.880, respectively) in distinguishing NPC patients and unaffected family members. EBV DNA load and EBV IgA serology demonstrate good sensitivity and specificity as screening tools. EBV-EA IgA gave the best sensitivity and specificity profile as a screening tool for NPC among high-risk family members.

Risks of high-risk sudden cardiac arrest family members to rescue strangers after CPR training

Objective To investigate the risks of high-risk sudden cardiac death (SCD) family members to rescue strangers after cardiopulmonary resuscitation (CPR) training. Methods A total of 11 SCD family members had been semi-structured interviewed. Data was analyzed using constant-comparative method. Results The risks of high-risk SCD family members to rescue strangers included insufficient self-ability, unfavorable social environment and uncertain effects. Conclusions High-risk SCD family members′ participation of CPR depends on their knowledge and evaluation of the risks. Key words: Sudden cardiac death; Cardiopulmonary resuscitation; Risk; Qualitative study

Exome Sequencing and Gene Prioritization Correct Misdiagnosis in a Chinese Kindred with Familial Amyloid Polyneuropathy.

Inherited neuropathies show considerable heterogeneity in clinical manifestations and genetic etiologies, and are therefore often difficult to diagnose. Whole-exome sequencing (WES) has been widely adopted to make definite diagnosis of unclear conditions, with proven efficacy in optimizing patients’ management. In this study, a large Chinese kindred segregating autosomal dominant polyneuropathy with incomplete penetrance was ascertained through a patient who was initially diagnosed as Charcot-Marie-Tooth disease. To investigate the genetic cause, forty-six living family members were genotyped by SNP microarrays, and one confirmed patient was subject to WES. Through systematic computational prioritization, we identified a missense mutation c.G148T in TTR gene which results in a p.V50L substitution known to cause transthyretin-related familial amyloid polyneuropathy. Co-segregation analysis and clinical follow-up confirmed the new diagnosis, which suggested new therapeutic options to the patients and informed high risk family members. This study confirms WES as a powerful tool in translational medicine, and further demostrates the practical utility of gene prioritization in narrowing the scope of causative mutation.

Abstract P2-09-10: Double heterozygosity for BRCA1 and BRCA2 pathogenic variants in a French metastatic breast cancer patient

Abstract Double heterozygosity is an extremely rare occurrence in hereditary breast and ovarian cancer syndrome (HBOC [MIM 604370; MIM 612555]) where two pathogenic variants, one in BRCA1 and one in BRCA2, are found in an individual. To date, only a few case reports and case series have been reported in the literature (1-3). Furthermore, little is known about the clinical characteristics, family history, and tumor histology in these patients. In this study, we utilized targeted gene testing with next-generation sequencing (NGS) technology in an early-onset metastatic breast cancer patient from France. We evaluated germline variants using Pathway Genomics' BRCATrueTM NGS test, which analyzes variants covering all exons and exon flanking regions in both the BRCA1 and BRCA2 genes. All variant calls were determined after alignment and mapping to the GRCh37/hg19 reference genome. Variant calls were confirmed by Sanger sequencing. In this patient, a c.1016dupA (p.V340GfsX6) frameshift variant was found in BRCA1 along with a c.6814delA (p.R2272EfsX8) frameshift variant in BRCA2. Both frameshift variants are predicted to truncate the BRCA proteins. The BRCA1 c.1016dupA variant is considered a Norwegian founder mutation but has also been observed in individuals who are of French-Canadian, French, Italian or Dutch ancestry (4-7). The BRCA2 c.6814delA (p.R2272Efs*8) pathogenic variant, also known as 7042delA, is predicted to truncate the BRCA2 protein and has been identified in individuals with a personal or family history of breast and/or ovarian cancer (8,9). To the best of our knowledge, the combination of these two pathogenic variants in an individual has not been previously reported. In a clinical diagnostic setting, the possibility of double heterozygosity of pathogenic variants in more than one susceptibility gene should be considered, especially in patients with early-onset metastatic cancers. Furthermore, genetic testing and genetic counseling should also be indicated for high-risk family members. 1. Heidemann, S. et al. (2012) Breast cancer research and treatment 134, 1229-1239 2. Lavie, O., et al. (2011) Annals of oncology : official journal of the European Society for Medical Oncology / ESMO 22, 964-966 3. Nomizu, T., et al. (2012). Breast cancer 4. Andersen, T. I., Borresen, A. L., and Moller, P. (1996) American journal of human genetics 59, 486-487 5. Caputo, S., et al. (2012) Nucleic acids research 40, D992-1002 6. Dorum, A., et al. (1999). American journal of human genetics 65, 671-679 7. Simard, J., et al. (1994). Nature genetics 8, 392-398 8. Novakovic, S., et al. (2012) International journal of oncology 41, 1619-1627 9. Tea, M. K., et al. (2014) Maturitas 77, 68-72. Citation Format: Curtit E, Meynard G, Villanueva C, Mansi L, Chaix M, Vilalta A, Kuo JZ, Villa M, Neidich J, Tomar A, Arianpour A, Lebahar P, Pivot X. Double heterozygosity for BRCA1 and BRCA2 pathogenic variants in a French metastatic breast cancer patient. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-09-10.