Family History Information Research Articles

Patient and provider perspectives on the development of personalized medicine: a mixed-methods approach.

While genetic testing gains adoption in specialty services such as oncology, neurology, and cardiology, use of genetic and genomic testing has yet to be adopted as widely in primary care. The purpose of this study is to identify and compare patient and primary care provider (PCP) expectations of genetics services in primary care. Patient and PCP perspectives were assessed through a mixed-method approach combining an online survey and semi-structured interviews in a primary care department of a large academic medical institution. A convenience sample of 100 adult primary care patients and 26 PCPs was gathered. The survey and interview questions focused on perceptions of genetic testing, experience with genetic testing, and expectations of genetic services in primary care. Patients felt that their PCP was knowledgeable about genetic testing and expected their PCP to be the first to recognize a need for genetic testing based on family history. Nonetheless, patients reported that PCPs rarely used family history information to discuss genetic risks or order testing. In contrast, PCPs felt uncertain about the clinical utility and scientific value of genetic testing. PCPs were concerned that genetic testing could cause anxiety, frustration, discrimination, and reduced insurability, and that there was unequal access to testing. PCPs described themselves as being "gatekeepers" to genetic testing but did not feel confident or have the desire to become experts in genetic testing. However, PCPs were open to increasing their working knowledge of genetic testing. Within this academic medical center, there is a gap between what patients expect and what primary care providers feel they are adequately prepared to provide in terms of genetic testing services.

A comparison of cancer risk assessment and testing outcomes in patients from underserved vs. tertiary care settings.

In cancer genetics, technological advances (next generation sequencing) and the expansion of genetic test options have resulted in lowered costs and increased access to genetic testing. Despite this, the majority of patients utilizing cancer genetics services lack diversity of gender, ethnicity, and socioeconomic status. Through retrospective chart review, we compared outcomes of cancer genetics consultations at a tertiary cancer center and a Federally Qualified Health Center (FQHC) (58 tertiary and 23 FQHC patients) from 2013 to 2015. The two groups differed in race, ethnicity, use of translator services, and type of insurance coverage. There were also significant differences in completeness of family history information, with more missing information about relatives in the FQHC group. In spite of these differences, genetic testing rates among those offered testing were comparable across the two groups with 74% of tertiary patients and 60% of FQHC patients completing testing. Implementation of community-based cancer genetics outreach clinics represents an opportunity to improve access to genetic counseling services, but more research is needed to develop effective counseling models for diverse patient populations.

Elevated Levels of Very Low-density Lipoprotein Cholesterol Independently Associated with In-stent Restenosis in Diabetic Patients after Drug-eluting Stent Implantation.

Background:High rate of in-stent restenosis (ISR) remained an unsolved clinical problem in clinical practice, especially among patients with diabetes mellitus (DM). Diabetic patients often had hypertriglyceridemia with elevated levels of very low-density lipoprotein cholesterol (VLDL-C). Increasing evidence suggested that VLDL-C was known as a significant risk factor for atherosclerosis and had been recommended as a treatment target by current dyslipidemia guidelines. However, the role of VLDL-C in the occurrence and development of ISR in coronary artery disease (CAD) patients with DM had not been studied. The aim of this study was to evaluate the association between the elevated levels of VLDL-C and the risk of ISR in CAD patients with DM.Methods:A total of 1390 diabetic patients, who underwent coronary drug-eluting stent (DES) implantation at Beijing Anzhen Hospital and followed up by angiography within 6–24 months, were consecutively enrolled. Patients’ demographic and clinical characteristics, including age, gender, CAD risk factors, family history, life style, medical history, and coronary angiographic information, were collected carefully at baseline percutaneous coronary intervention and follow-up angiography. Multivariate Cox's proportional hazards regression modeling using the step-wise method (entry, 0.05; removal, 0.05) was used to determine the independent risk associated with ISR in diabetic patients.Results:Finally, 1206 of patients were included in this study. ISR occurred in 132/1206 diabetic patients (10.9%) by follow-up angiography. Patients with ISR had elevated median serum VLDL-C levels compared with those without ISR (0.65 mmol/L vs. 0.52 mmol/L, P = 0.030). The multivariate regression analysis showed that VLDL-C was significantly associated with the risk of ISR in diabetic CAD patients (hazard ratio [HR] = 1.15, 95% confidence interval [CI]: 1.03–1.29, P = 0.017). The HR for the risk of ISR associated with VLDL-C level ≥0.52 mmol/L was 3.01 (95% CI: 1.24–7.34, P = 0.015).Conclusion:The elevated level of serum VLDL-C was a significant and independent risk factor for ISR in diabetic CAD patients after coronary DES implantation.

In Silico Systems Biology Analysis of Variants of Uncertain Significance in Lynch Syndrome Supports the Prioritization of Functional Molecular Validation.

Lynch syndrome (LS) is a genetic condition secondary to germline alterations in the DNA mismatch repair (MMR) genes with 30% of changes being variants of uncertain significance (VUS). Our aim was to perform an in silico reclassification of VUS from a large single institutional cohort that will help prioritizing functional validation. A total of 54 VUS were detected with 33 (61%) novel variants. We integrated family history, pathology, and genetic information along with supporting evidence from eight different in silico tools at the RNA and protein level. Our assessment allowed us to reclassify 54% (29/54) of the VUS as probably damaging, 13% (7/54) as possibly damaging, and 28% (15/54) as probably neutral. There are more than 1,000 VUS reported in MMR genes and our approach facilitates the prioritization of further functional efforts to assess the pathogenicity to those classified as probably damaging. Cancer Prev Res; 10(10); 580-7. ©2017 AACR.

Abstract 434: The Majority of Outpatients With Severe Hypercholesterolemia at an Academic Tertiary Centre Have Not Been Screened for FH

Background: National and International guidelines recommend, as a minimum, that individuals with LDL-C ≥190mg/dL are asked about a family history of ASCVD and hypercholesterolemia to screen for familial hypercholesterolemia (FH), a monogenic condition that carries considerable ASCVD risk. However, FH is grossly underdiagnosed and undertreated in the US. One reason for this may be failure to screen severely hypercholesterolemic individuals for FH. Hypothesis: We evaluated the hypothesis that poor identification of FH might be due to inadequate screening for FH among individuals with severe hypercholesterolemia. Methods: An EHR query was used to identify active adult patients in the University of Pennsylvania outpatient EHR database (N=310 802) with LDL-C≥220mg/dL, excluding secondary causes of hypercholesterolemia. The EHR was then systematically reviewed for structured notation of family history information. Result: The query identified 3,475 individuals with severely elevated LDL-C. Among them, only 47.9% (1666) had family history data relating to ASCVD (968), hypercholesterolemia (336) or both (362) in the EHR. The history was positive in 94.2% (1569) of these cases. Overall, patients with LDL-C ≥220mg/dL were more likely to be screened (OR 1.57; 95% CI 1.47-1.68) than those with LDL <220mg/dL. Within the former group, the odds of being screened were higher in Caucasians (OR 1.52; 95% CI 1.33-1.75), with more severe LDL-C elevation or a history of ASCVD (OR 1.36; 95% CI 1.10 - 1.67). Conversely, the presence of diabetes (OR 0.73; 95% CI 0.61-0.86) or hypertension (OR 0.82; 95% CI 0.72-0.94), made screening less likely to occur. Interestingly, the setting of clinical care was also important; individuals seen in secondary care (OR 1.68; 95% CI 1.41-2.26), general (OR 1.69, 95% CI 1.47-1.95) or preventative cardiology (OR 1.82; 95% CI 1.47-2.25) were more likely to be screened. Finally, statin prescription was more common in those screened (OR 1.39; 95% CI 1.16-1.88), but this did not affect LDL-C goal achievement. Conclusion: At a large academic centre, the majority of outpatients with severe hypercholesterolemia had no record of being screened for FH. This report sheds light on factors that might be relevant to the underdiagnosis of FH in the US.

Positive family history of aortic dissection dramatically increases dissection risk in family members

ObjectivesAlthough family members of patients with aortic dissection (AoD) are believed to be at higher risk of AoD, the prognostic value of family history (FH) of aortic dissection (FHAD) in family members of patients with AoD has not been studied rigorously. We seek examine how much a positive FHAD increases the risk of developing new aortic dissection (AoD) among first-degree relatives. MethodsPatients with AoD at our institution were analyzed for information of FHAD. Positive FHAD referred to that AoD occurred in index patient and one or more first-degree relatives. Negative FHAD was defined as the condition in which only one case of AoD (the index patient) occurred in the family. The age at AoD, exposure years in adulthood before AoD, and annual probability of AoD among first-degree relatives were compared between patients with negative and positive FHADs. ResultsFHAD was positive in 32 and negative in 68 among the 100 AoD patients with detailed family history information. Mean age at dissection was 59.9±14.7years. Compared to negative FHAD, patients with positive FHAD dissected at significantly younger age (54.7±16.8 vs 62.4±13.0years, p=0.013), had more AoD events in first-degree relatives (2.3±0.6 vs 1.0±0.0, p<0.001), and shorter exposure years per AoD event (18.3±6.7 vs 43.1±8.5, p<0.001). Annual probability of AoD per first-degree relative was 2.77 times higher in patients with positive than negative FHADs (0.0100±0.0057 vs 0.0036±0.0014, p<0.001). ConclusionsA positive FHAD confers a significantly increased risk of developing aortic dissection on family members, with a higher annual probability of aortic dissection, a shorter duration of “exposure time” before dissection occurs and a lower mean age at time of dissection.

MP33-11 GENETIC RISK SCORE CAN DISTINGUISH RISK OF PROSTATE CANCER AMONG FAMILY MEMBERS WITH SIMILAR DEGREES OF RELATIONSHIP

You have accessJournal of UrologyProstate Cancer: Detection & Screening III1 Apr 2017MP33-11 GENETIC RISK SCORE CAN DISTINGUISH RISK OF PROSTATE CANCER AMONG FAMILY MEMBERS WITH SIMILAR DEGREES OF RELATIONSHIP Brian Helfand, Haitao Chen, Rong Na, Carly Conran, William Catalona, and Jianfeng Xu Brian HelfandBrian Helfand More articles by this author , Haitao ChenHaitao Chen More articles by this author , Rong NaRong Na More articles by this author , Carly ConranCarly Conran More articles by this author , William CatalonaWilliam Catalona More articles by this author , and Jianfeng XuJianfeng Xu More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1007AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Family history is a well-established risk factor for prostate cancer (PCa). However, family history information assigns equivalent risk to all relatives based upon the degree of relationship. Recent genetic studies have identified single nucleotide polymorphisms (SNPs) that can be used to calculate a genetic risk score (GRS) to determine an individual′s PCa risk. We sought to determine whether GRS can better estimate PCa risk among individuals with a family history of PCa. METHODS Patients evaluated at a tertiary referral clinic with a family history of PCa were recruited for this study and were genotyped for 26 SNPs previously associated with PCa. The degree of familial risk (F) was calculated for each subject based on PCa among his relatives (e.g. F value of 0.5= 1 first-degree relative with PCa or 2 second-degree relatives with PCa). A GRS value was also calculated for each subject using 26 SNPs. Analyses comparing the distribution of GRS values among affected and unaffected family members with varying F values were performed. RESULTS Subjects from 811 families with at least two affected members were included. The median GRS was significantly higher among family members with PCa (median 1.31; range 0.21-11.64) compared to unaffected family members (median 1.03; range 0.18-6.32; p=9.69e-8). There was a wide distribution of GRS values among members of each F group (Table). Higher GRS values were significantly associated with increased PCa risk among all F groups (p<0.05). For example, among subjects with F values of 1-1.49, PCa patients had a high mean GRS (1.64) than non-PCa subjects (1.12), P=0.0015. Multivariate models to assess the associations between age, GRS, F value and PCa diagnosis demonstrate that higher GRS (P=1.36e-7) and higher F values (P=2.64e-9) were independently associated with increased PCa risk. CONCLUSIONS GRS is an objective measurement that allows for differentiation of PCa risk among family members with similar degrees of familial risk of PCa. While prospective validation studies are required, this information can help guide relatives in regards to the time of initiation and frequency of PCa screening. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e421 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Brian Helfand More articles by this author Haitao Chen More articles by this author Rong Na More articles by this author Carly Conran More articles by this author William Catalona More articles by this author Jianfeng Xu More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Insights from early experience of a Rare Disease Genomic Medicine Multidisciplinary Team: a qualitative study

Whole-exome/whole-genome sequencing (WES/WGS) has the potential to enhance genetic diagnosis of rare disease, and is increasingly becoming part of routine clinical care in mainstream medicine. Effective translation will require ongoing efforts in a number of areas including: selection of appropriate patients, provision of effective consent, pre- and post-test genetic counselling, improving variant interpretation algorithms and practices, and management of secondary findings including those found incidentally and those actively sought. Allied to this is the need for an effective education programme for all members of clinical teams involved in care of patients with rare disease, as well as to maintain public confidence in the use of these technologies. We established a Genomic Medicine Multidisciplinary Team (GM-MDT) in 2014 to build on the experiences of earlier successful research-based WES/WGS studies, to address these needs and to review results including pertinent and secondary findings. Here we report on a qualitative study of decision-making in the GM-MDT combined with analysis of semi-structured interviews with GM-MDT members. Study findings show that members appreciate the clinical and scientific diversity of the GM-MDT and value it for education and oversight. To date, discussions have focussed on case selection including the extent and interpretation of clinical and family history information required to establish likely monogenic aetiology and inheritance model. Achieving a balance between effective use of WES/WGS – prioritising cases in a diverse and highly complex patient population where WES/WGS will be tractable – and meeting the recruitment targets of a large project is considered challenging.

Abstract S2-03: Does BRCA status affect outcome in young breast cancer patients? Results from the prospective study of outcomes in sporadic and hereditary breast cancer (POSH)

Abstract Background Germline mutations in BRCA1/2 account for ∼3% of breast cancer cases but &amp;gt;10% of young patients who present with triple negative (TN) breast cancer. Young age at diagnosis is also associated with an increased risk of recurrence and inferior survival compared to older patients. Numerous publications describe an increased incidence of adverse biological features in tumours from young breast cancer patients; however it is unclear whether these fully explain the poor outcome. The effect of carrying a BRCA1/2 mutation on the prognosis of breast cancer remains controversial with retrospective studies reporting better, similar and worse outcomes for mutation carriers compared to patients with sporadic tumours. BRCA carriers could feasibly have enhanced or reduced sensitivity to certain chemotherapeutics; however retrospective studies are problematic due to missing data and biased ascertainment. POSH is multicentre prospective observational cohort study designed to investigate factors which affect prognosis in young breast cancer patients (Copson et al, JNCI, 2013). Here we report the pathology, treatment and outcome of patients with TN tumours as a preliminary analysis to determine the impact of a germline BRCA1 mutation on survival. The whole cohort analysis including BRCA1 and BRCA2 is in progress. Methods 2956 patients aged ≤40 at breast cancer diagnosis were recruited from 127 UK oncology centres between 2000 and 2008. Patient characteristics, family history, risk factors, tumour pathology and treatment information, and blood DNA were collected at recruitment. Follow-up data were collected at 6 and 12 months, then annually. Summary statistics were used to describe patients by BRCA1 status. Kaplan-Meier estimates were used to describe univariate survival data. Results BRCA1 status is currently available for 542 patients with TN tumours. Pathogenic BRCA1 mutations were identified in 122 patients (BRCA1+); 420 had no BRCA1 mutation (BRCA1-). BRCA1+ were younger than BRCA1- (median age 34 vs 36 years, p&amp;lt;0.001) and more likely to have a positive family history (p&amp;lt;0.001). There were no significant differences between BRCA1+ vs BRCA1- for: median tumour size (20.8mm vs 23.0mm); tumour grade distribution (95.8% grade 3 vs 93.6%); nodal involvement (35.2% node positive vs 39.9%); or presence of metastases at diagnosis (0.0% vs 1.0%). Median follow-up was 7.3 years. Overall survival of patients with stage 1-3 disease treated with anthracycline +/- taxane neoadjuvant chemotherapy (n=538; 151 deaths) was better for BRCA1+ vs BRCA1- (79.1% vs 73.6% at 5-yrs; HR[95%CI]=0.84[0.57,1.25],p=0.388). Distant disease-free survival (DDFS) was also higher for BRCA1+ (5-yr DDFS 76.1% vs 71.5%; HR[CI]=0.92[0.63,1.35], p=0.682). Moreover, survival after first distant relapse was better for BRCA1+ patients (41.9% vs 36.8% at 1-yr; HR[CI]=0.78[0.51,1.18], p=0.233). Conclusions Our prospective data show better survival in young BRCA1+ patients with early TN breast cancer treated with anthracycline/-taxane chemotherapy than BRCA1- patients. However, the difference between the groups was not significant in this partial sample. Results for the whole cohort will be available by the time of the meeting. Citation Format: Eccles DM, Copson ER, Maishman T, Tapper W, Cutress R, Gerty S, Stanton L, Altman DG, Durcan L, Simmonds P, Decker B, Allen J, Luccarini C, Easton D, Dunning A, POSH Steering Group and Collaborators. Does BRCA status affect outcome in young breast cancer patients? Results from the prospective study of outcomes in sporadic and hereditary breast cancer (POSH) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr S2-03.

Abstract P5-03-08: Use of natural language processing on mammography and pathology findings to supplement BI-RADS to improve clinical decision making in breast cancer care

Abstract Breast Imaging Reporting and Data System (BI-RADS) is a standard system used by clinicians to describe mammogram findings and sort the results into categories numbered 0 through 6; this makes accurately communicating about these test results and following up after the tests much easier. For example, the BI-RADS 4 score is given to lesions that carry a risk of malignancy between 2 and 95% such that a majority (69 to 95%) of BI-RADS 4 lesions are biopsied. Our goal is to create a better risk estimate score to stratify patients by developing a more accurate threshold for biopsy. To accomplish this goal, we defined the personal risk factors, relevant descriptors in the mammography and pathology findings for every patient with BI-RADS 3, 4, or 5 risk score. Clinical data were sourced from the Methodist Environment for Translational and Outcomes Research (METEOR) data warehouse at the Houston Methodist Hospital. METEOR data warehouse contains 135,280 unique patient mammogram reports dating from January 1, 2006 to May 30, 2015. Manual abstraction from this large number of free text reports is not feasible due to the constraints on time and labor costs, and risk of human-error during manual extraction. We developed a natural language processing (NLP) tool called Methodist hOspital Text Teaser (MOTTE) to extract defined clinical parameters and derive the desired meaning from the volumes of free text reports automatically. MOTTE is a rule-based software tool programmed in Java, Structured Query Language (SQL) and an open source machine learning toolkit, OpenNLP. MOTTE combines regular expressions and algorithms to identify where in the dictionary keywords and phrases related to a concept are found. Mammography findings from January 2006 to May 2015 were extracted including breast density as well as the presence of mass, calcifications, architectural distortion, asymmetric density, and calcification characteristics. A total of 717 patients with BI-RADS 5 mammograms who underwent breast biopsy within 3 months of the abnormal mammogram report date were identified using MOTTE, which also extracted personal history, family history, and subtype information (ER, PR, and HER2 status) of those patients. Clinical data including age, race, height, weight, and body mass index (BMI) were extracted from the METEOR data warehouse for those 717 patients. The extracted data were verified and validated with 99% accuracy by assessing a random 10% of records against a gold standard of manual chart review, which was completed by the clinical coauthors. MOTTE surpasses the manual method in terms of consistency, time, cost, and data preparation. Our ongoing study is to apply the MOTTE to extract distinct characteristics of BI-RADS 4 scored patients. The finding would help to refine biopsy recommendations and create a predictive model to drive evidence-based biopsy decision-making in breast cancer care. Citation Format: Puppala M, He TC, Ogunti R, Wong STC. Use of natural language processing on mammography and pathology findings to supplement BI-RADS to improve clinical decision making in breast cancer care [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-03-08.

Genetic and epigenetic characterization of the BRCA1 gene in Brazilian women at-risk for hereditary breast cancer.

This study aimed to characterize women at-risk for hereditary BC regarding their clinical and molecular characteristics (mutation and methylation in the BRCA1 gene) and correlate the gene expression levels with histopathological, clinical and family history information. BRCA1 real time qPCR was performed to evaluate methylation status and gene expression. The study included 88 women grouped according to the BRCA1 mutational status: 23 BRCA1 mutated, 22 with a Variant of Unknown Significance (VUS) in BRCA1 and 43 BRCA1 WT. Most BRCA1 mutated tumors were triple negative (69.6%) and had histologic grade III (61.0%). Patients with VUS/WT BRCA1 were predominantly of luminal B subtype with histological grades I and II. Regarding the methylation profile, BRCA1 hypermethylation was observed in only two patients (both WT) and none had association with pathogenic BRCA1 mutation. In one patient methylation was present in both, tumor and normal tissues. Hypermethylated tumors had ductal histology, negativity for ER and occurred in < 50 years patients. Gene expression profile showed in all groups lower BRCA1 mRNA levels in tumor tissue compared to the adjacent breast tissue, thereby indicating the loss/decrease of gene function. No association was found between the levels of BRCA1 gene expression and family history of cancer. In summary, our findings suggested that methylation at the BRCA1 gene is not the “second” event in the development of BC in patients with germline mutations in BRCA1 and, although rare, BRCA1 epimutations can constitute an explanation for a fraction of HBOC families.

Personalized, Genomic-Based Care Could Mean a Paradigm Shift

Personalized, Genomic-Based Care Could Mean a Paradigm Shift

Abstract 11807: Phenotyping Family History of Coronary Heart Disease to Inform Risk Assessment for Cardiovascular Events in MESA

Introduction: The relationships between various family history (FH) of coronary heart disease (CHD) phenotypes and cardiovascular disease (CVD) events have not been fully explored. Hypothesis: The association between FH and CVD will differ by, 1) FH at any age vs. premature FH in a parent, sibling, or child, and 2) familial risk score strata (weak, moderate, or strong; see Table for details). Methods: We ascertained CVD events (CHD, angina, stroke, peripheral arterial disease [PAD], and heart failure [HF]) over a median of 10.1 years. Multivariable Cox models examined the association of FH with CVD events (individual and composite). The C-statistic assessed the prognostic impact of FH for predicting CVD when added to traditional RFs. Results: Of 6192 adults [mean (±SD) age 62±10 years, 48% men, 40% white] with information on FH, 36% reported any FH. Those with strong familial risk (n=1240) were more likely to be diabetic, overweight, smoke, or take medication for hypertension and dyslipidemia. Overall, 741 CVD events occurred. Compared to no FH, any FH was associated with incident CHD, angina, and composite CVD in adjusted models [hazard ratio (95% CI)]: 1.4 (1.1-1.8), 1.6 (1.2-2.1), and 1.3 (1.1-1.5), respectively]. Nearly identical results were obtained for premature FH ( Table ). Compared to weak familial risk, strong risk was also associated with CHD, angina and CVD. However, there was no association between FH of any type and stroke, PAD, or HF. FH status (any or premature) and familial risk score improved discrimination of CVD (p =0.0005, p=0.005, and p=0.001, respectively). Familial risk score provided marginal discrimination over and above premature FH status (C statistic from 0.742 to 0.744, p=0.051). Conclusion: The association between FH and CVD risk differs depending on the number of affected family members, suggesting the value of detailed FH information to refine risk assessment. The predictive value of FH of CHD for non-coronary events is limited.

Why Is Cancer Genetic Counseling Underutilized by Women Identified as at Risk for Hereditary Breast Cancer? Patient Perceptions of Barriers Following a Referral Letter.

Family history information comprises an important tool in identifying and referring patients at risk for hereditary breast and ovarian cancer (HBOC) to cancer genetic counseling. Despite recommendations and support provided by numerous professional organizations, cancer genetic counseling services are underutilized by atrisk patients. This study aimed to: (1) determine the rate of genetic counseling utilization following a referral letter, (2) characterize factors (barriers and supports) which influenced uptake of services, and (3) identify potential strategies for increasing utilization. This study evaluated the uptake of cancer genetic counseling among 603 screening mammography patients identified as having an increased risk for HBOC based on National Comprehensive Cancer Network (NCCN) guidelines. At risk individuals and their primary care providers were mailed a referral letter recommending genetic counseling. Three focus groups (N=24) were conducted to identify responses to receiving a letter recommending genetic counseling, barriers to seeking genetic counseling, and facilitating factors to utilizing these services. Participant responses were qualitatively analyzed using thematic and cross case analysis. Within one year, 50/603 (8%) of the identified at-risk women completed a genetic counseling appointment. Participant-perceived barriers which influenced their decision not to seek genetic counseling included lack of relevance and utility, limited knowledge about genetic counseling, concerns about the genetic counseling process, and concerns about cost and insurance coverage. Participant-perceived facilitating factors which would support a decision to seek genetic counseling included greater awareness and education about genetic counseling services when receiving a referral, and improved follow up and guidance from their provider. Findings from this study support the need for patient and primary care provider education, and improved provider-patient communication to increase uptake of genetic counseling services.

Dominant Transmission Observed in Adolescents and Families With Orthostatic Intolerance

BackgroundOrthostatic intolerance is typically thought to be sporadic and attributed to cerebral autonomic dysfunction. We sought to identify families with inherited autonomic dysfunction manifest as symptomatic orthostatic intolerance to characterize mode of inheritance and clinical features. MethodsSixteen families with two or more first- or second-degree relatives with autonomic dysfunction and orthostatic intolerance were enrolled. A clinical diagnosis of autonomic dysfunction defined by symptomatic orthostatic intolerance diagnosed by head-up tilt table testing was confirmed for each proband. Clinical features and evaluation were obtained from each proband using a standardized intake questionnaire, and family history information was obtained from probands and available relatives. ResultsComprehensive pedigree analysis of 16 families (39 individuals with orthostatic intolerance and 40 individuals suspected of having orthostatic intolerance) demonstrated dominant transmission of autonomic dysfunction with incomplete penetrance. Affected individuals were predominantly female (71.8%, 28/39; F:M, 2.5:1). Male-to-male transmission, although less common, was observed and demonstrated to transmit through unaffected males with an affected parent. Similar to sporadic orthostatic intolerance, probands report a range of symptoms across multiple organ systems, with headaches and neuromuscular features being most common. ConclusionsFamilial occurrence and vertical transmission of autonomic dysfunction in 16 families suggest a novel genetic syndrome with dominant transmission, incomplete penetrance, and skewing of the sex ratio. Elucidation of potential genetic contributions to orthostatic intolerance may inform therapeutic management and identification of individuals at risk. Adolescent evaluation should include identification and treatment of potential at-risk relatives.

Urologists' Current Practices in Screening and Treating Men With a Family History of Prostate Cancer

To assess urologists' knowledge and utilization of family history to determine prostate cancer (PC) screening and treatment recommendations. Questionnaires that explored urologists' knowledge, frequency, and utilization of family history information for screening and treatment recommendations for PC were prospectively collected. Data were summarized and compared using descriptive statistics. A total of 87 responses were collected, for a response rate of 60% (87 of 145). The majority of urologists reported that they always collect family history when discussing risk (95%) or screening (87%), and recommended earlier screening for men with family history of PC in comparison with men with no family history. Although only 57% reported always collecting family history when discussing treatment, the majority of respondents reported that a positive family history influenced their treatment recommendations. Eight percent of urologists would recommend prostatectomy for men diagnosed with low-grade, low-risk PC and no family history of PC vs 52% who would recommend the same course of treatment when the patient had at least 1 first-degree relative who died of the disease. Conversely, 91% of urologists would recommend active surveillance for men with low-grade, low-risk PC and no family history vs 47% for those with at least 1 first-degree relative who died of the disease. The majority of urologists collect information on family history of PC. Despite the lack of literature to support that patients with familial PC require more aggressive treatment, urologists were more likely to recommend definitive therapies.

Further Evidence of a Cohort Effect in Bipolar Disorder: More Early Onsets and Family History of Psychiatric Illness in More Recent Epochs.

Given that a cohort effect is rarely mentioned as one of the possible contributors to the increased incidence of childhood-onset bipolar disorder in the United States, we reexamined evidence for the phenomenon within our outpatient Bipolar Collaborative Network. 968 outpatients (mean age, 41 years) with DSM bipolar disorder from 1995 to 2002 from 4 sites in the United States and 3 in the Netherlands and Germany (abbreviated as Europe) gave informed consent and provided detailed demographic, illness, and family history information on a patient questionnaire. Family history of bipolar disorder, depression, suicide attempt, alcohol abuse, substance abuse, and "other" illness was collected for each parent and the 4 grandparents. Age at onset and family history of illness burden were then assessed as a function of the age of the patient at network entry. Data for patients aged 35 years or older (n = 613) were included in the first analysis. Compared to older patients, those who were younger when they entered the network had an earlier age at onset of their bipolar disorder (r = 0.33, P < .001). Similarly, the youngest patients at entry (representing the most recent cohorts) had parents and grandparents with more psychiatric illness than patients born in earlier cohorts (n = 968). These preliminary data, taken with the substantial literature, suggest a cohort effect for earlier age at onset of bipolar disorder and greater burden of psychiatric disorders in 2 generations of direct progenitors of our patients. The resulting likely increase in severity of bipolar illness in future generations based on this earlier age at onset and increased familial loading, particularly in the United States, deserves focused clinical and public health attention and attempts at amelioration.

A model for patient-direct screening and referral for familial cancer risk.

Patients at increased familial risk of cancer are sub-optimally identified and referred for genetic counseling. We describe a systematic model for information collection, screening and referral for hereditary cancer risk. Individuals from three different clinical and research populations were screened for hereditary cancer risk using a two-tier process: a 7-item screener followed by review of family history by a genetic counselor and application of published criteria. A total of 869 subjects participated in the study; 769 in this high risk population had increased familial cancer risk based on the screening questionnaire. Of these eligible participants, 500 (65.0%) provided family histories and 332 (66.4%) of these were found to be at high risk of a hereditary cancer syndrome, 102 (20.4%) at moderate familial cancer risk, and 66 (13.2%) at average risk. Three months following receipt of the risk result letter, nearly all respondents found the process at least somewhat helpful (98.4%). All participants identified as high-risk were mailed a letter recommending genetic counseling and were provided appointment tools. After 1year, only 13 (7.3%) of 179 high risk respondents reported pursuit of recommended genetic counseling. Participants were willing to provide family history information for the purposes of risk assessment; however, few patients pursued recommended genetic services. This suggests that cancer family history registries are feasible and viable but that further research is needed to increase the uptake of genetic counseling.

Family History-Taking in Paediatrics: It’s Much More Than Just A Checklist

Abstract BACKGROUND: Family history (FH) is a risk factor for many conditions in pediatric practice; interest has increased in supporting systematic FH taking in this area by identifying core conditions for enquiry and developing point of care tools. There is little published about current practice to inform implementing such changes. OBJECTIVES: To inform future FH taking interventions by identifying pediatricians' perceptions, attitudes, beliefs, and current practices. DESIGN/METHODS: The Theoretical Domains Framework (TDF) was used to develop a comprehensive interview scheme. Semi-structured interviews were conducted with community and hospital-based pediatricians Analysis was by the constant comparison method, using a thematic approach. This study was funded by the Canadian Institutes of Health Research. RESULTS: The data revealed FH taking to be a firmly embedded, but complex aspect of pediatric practice. Participants described FH as part of regular, holistic care, extending to social and interpersonal, as well as clinical purposes; in addition to disease risk assessment, FH information helped clarify diagnosis, and select medication; tailor the overall patient management based on family circumstances; and provide psychosocial support for parents. It was also used as a method to build a relationship with parents/carers. FH and social history information were inextricably linked and often appeared to be the same concept in participants’ minds. Participating pediatricians generally expressed confidence in their FH skills and reported tailoring their approach according to experience, after initial training early in their career. While acknowledging some challenges in ensuring accuracy, they were attuned to nuances in their interactions with parents and children which would affect whether, and what, they were told about illness in the family. Most were not concerned about formal evidence, and would not change their practice except for “good reason”. CONCLUSION: The use of the TDF helped ensure a comprehensive approach to FH taking in pediatric practice. The findings suggest that FH taking in this setting is a complex activity, embedded in routine care. Recommendations for systematic enquiry about specific conditions cannot be seen as a simple additional activity to current practice. Efforts to make FH taking more systematic may founder if they fail to take into account pediatricians’ attitudes, perspectives, and practices. Further studies should explore and seek to confirm and expand our observations.

Effectiveness of Home Blood Pressure Monitoring Among Low-Income Adults in Rural Appalachia.

High blood pressure (BP) is a common chronic condition in the United States. For many people, BP control through pharmacologic intervention alone is not effective at maintaining a healthy BP. Team-based, patient-focused care and home-based BP monitoring in addition to pharmacologic interventions have been shown to be effective for controlling BP. To determine the effectiveness of the hypertension management program at the Heritage Community Clinic in Athens, Ohio. Medical records of 43 patients who took part in the hypertension management program were retrospectively reviewed and included clinical data such as age, sex, BP, body mass index, comorbidities, family history, and demographic information. In addition to standard pharmacologic interventions, the program provided equipment for at-home BP monitoring, education on behavior and lifestyle modification, and 5 follow-up visits. Data from the 5 follow-up visits were analyzed. Linear mixed-effects regression models of BP suggested that the visit factor was significantly associated with BP (P<.001). On average at each visit, patients showed a 6.8-mm Hg reduction in systolic BP and a 3.8-mm Hg reduction in diastolic BP after controlling for demographic variables. General stress level, marital status, and depression were all significantly associated with BP (P<.05). In addition, 67.5% of the patients who took part in this program achieved the target treatment guidelines of the Eighth Joint National Committee for hypertension management. A clinic-based hypertension management program comprising patient education, support, medication, and home BP monitoring was effective at reducing BP.