The uptake of family screening in hypertrophic cardiomyopathy and an online video intervention to facilitate family communication.
ABSTRACT: BACKGROUND:Individuals with hypertrophic cardiomyopathy (HCM), even when asymptomatic, are at-risk for sudden cardiac death and stroke from arrhythmias, making it imperative to identify individuals affected by this familial disorder. Consensus guidelines recommend that first-degree relatives (FDRs) of a person with HCM undergo serial cardiovascular evaluations. METHODS:We determined the uptake of family screening in patients with HCM and developed an online video intervention to facilitate family communication and screening. Family screening and genetic testing data were collected through a prospective quality improvement initiative, a standardized clinical assessment and management plan (SCAMP), utilized in an established cardiovascular genetics clinic. Patients were prescribed an online video if screening of their FDRs was incomplete and a pilot study on video utilization and family communication was conducted. RESULTS:Two-hundred and sixteen probands with HCM were enrolled in SCAMP Phase I and 190 were enrolled in SCAMP Phase II. In both phases, probands reported that 51% of FDRs had been screened (382/749 in Phase I, 258/504 in Phase II). Twenty patients participated in a pilot study on video utilization and family communication. Nine participants reported watching the video and six participants reported sharing the video with relatives; however only one participant reported sharing the video with relatives who were not yet aware of the diagnosis of HCM in the family. CONCLUSION:Despite care in a specialized cardiovascular genetics clinic, approximately one half of FDRs of patients with HCM remained unscreened. Online interventions and videos may serve as supplemental tools for patients communicating genetic risk information to relatives.
Project description:Importance:Breast cancer screening guidelines acknowledge the need for earlier screening for women at increased risk but provide limited guidance for women with a family history of breast cancer. A risk-adapted starting age of screening for relatives of patients with breast cancer may help supplement current screening guidelines. Objective:To identify the risk-adapted starting age of breast cancer screening on the basis of a woman's detailed family history. Design, Setting, and Participants:This nationwide cohort study analyzed data recorded in the Swedish family-cancer data sets. All women born from 1932 onward and with at least 1 known first-degree relative (FDR) were included (N?=?5?099?172). Data from January 1, 1958, to December 31, 2015, were collected. Data were analyzed from October 1, 2017, to March 31, 2019. Exposures:Family history of breast cancer in FDRs and second-degree relatives (SDRs). Main Outcomes and Measures:Primary invasive breast cancer diagnosis and the age at which women with different constellations of family history attained the risk level at which breast screening is usually recommended. Results:Of the 5?099?172 women included in the study, 118?953 (2.3%) received a diagnosis of primary invasive breast cancer. A total of 102?751 women (86.4%; mean [SD] age at diagnosis, 55.9 [11.1] years) did not have family history of breast cancer in FDRs and SDRs at the time of their diagnosis. Risk-adapted starting age of breast cancer screening varied by number of FDRs and SDRs with breast cancer diagnosis and the age at diagnosis of the FDRs. For example, for screening recommendation at age 50 years for the general population (2.2% 10-year cumulative risk), women with multiple affected FDRs, with the youngest affected relative receiving a diagnosis before age 50 years, reached the benchmark risk level at age 27 years. When the youngest relative received a diagnosis after age 50 years, however, this risk level was attained at age 36 years. Conclusions and Relevance:This study identifies possible risk-based starting ages for breast cancer screening based on population-based registers. These results may serve as high-quality evidence to supplement current screening guidelines for relatives of patients with breast cancer.
Project description:BACKGROUND & AIMS:Relative risk of colorectal cancer (CRC) decreases with age among individuals with a family history of CRC. However, no screening recommendations specify less frequent screening with increasing age. We aimed to determine whether such a refinement would be cost effective. METHODS:We determined the relative risk for CRC for individuals based on age and number of affected first-degree relatives (FDRs) using data from publications. For each number of affected FDRs, we used the Microsimulation Screening Analysis model to estimate costs and effects of colonoscopy screening strategies with different age ranges and intervals. Screening was then optimized sequentially, starting with the youngest age group, and allowing the interval of screening to change at certain ages. Strategies with an incremental cost effectiveness ratio below $100,000 per quality-adjusted life year were considered cost effective. RESULTS:For people with 1 affected FDR (92% of those with a family history), screening every 3 years beginning at an age of 40 years is most cost effective. If no adenomas are found, the screening interval can gradually be extended to 5 and 7 years, at ages 45 and 55 years, respectively. From a cost-effectiveness perspective, individuals with more affected FDRs should start screening earlier and at shorter intervals. However, frequency can be reduced if no abnormalities are found. CONCLUSIONS:Using a microsimulation model, we found that for individuals with a family history of CRC, it is cost effective to gradually increase the screening interval if several subsequent screening colonoscopies have negative results and no new cases of CRC are found in family members.
Project description:BACKGROUND:Schizophrenia and bipolar disorder share genetic liability, and some structural brain abnormalities are common to both conditions. First-degree relatives of patients with schizophrenia (FDRs-SZ) show similar brain abnormalities to patients, albeit with smaller effect sizes. Imaging findings in first-degree relatives of patients with bipolar disorder (FDRs-BD) have been inconsistent in the past, but recent studies report regionally greater volumes compared with control subjects. METHODS:We performed a meta-analysis of global and subcortical brain measures of 6008 individuals (1228 FDRs-SZ, 852 FDRs-BD, 2246 control subjects, 1016 patients with schizophrenia, 666 patients with bipolar disorder) from 34 schizophrenia and/or bipolar disorder family cohorts with standardized methods. Analyses were repeated with a correction for intracranial volume (ICV) and for the presence of any psychopathology in the relatives and control subjects. RESULTS:FDRs-BD had significantly larger ICV (d = +0.16, q < .05 corrected), whereas FDRs-SZ showed smaller thalamic volumes than control subjects (d = -0.12, q < .05 corrected). ICV explained the enlargements in the brain measures in FDRs-BD. In FDRs-SZ, after correction for ICV, total brain, cortical gray matter, cerebral white matter, cerebellar gray and white matter, and thalamus volumes were significantly smaller; the cortex was thinner (d < -0.09, q < .05 corrected); and third ventricle was larger (d = +0.15, q < .05 corrected). The findings were not explained by psychopathology in the relatives or control subjects. CONCLUSIONS:Despite shared genetic liability, FDRs-SZ and FDRs-BD show a differential pattern of structural brain abnormalities, specifically a divergent effect in ICV. This may imply that the neurodevelopmental trajectories leading to brain anomalies in schizophrenia or bipolar disorder are distinct.
Project description:BACKGROUND:Coronary Artery Disease (CAD) is clearly a multifactorial disease that develops from childhood and ultimately leads to death. Several reports revealed having a First Degree Relatives (FDRS) with premature CAD is a significant autonomous risk factor for CAD development. C - reactive protein (CRP) is a member of the pentraxin family and is the most widely studied proinflammatory biomarker. IL-18 is a pleiotrophic and proinflammatory cytokine which is produced mainly by macrophages and plays an important role in the inflammatory cascade. METHODS AND RESULTS:Hs-CRP levels were estimated by ELISA and Genotyping of IL-18 gene variant located on promoter -137 (G/C) by Allele specific PCR in blood samples of 300 CAD patients and 300 controls and 100 FDRS. Promoter Binding sites and Protein interacting partners were identified by Alibaba 2.1 and Genemania online tools respectively. Hs-CRP levels were significantly high in CAD patients followed by FDRS when compared to controls. In IL-18 -137 (G/C) polymorphism homozygous GG is significantly associated with occurrence of CAD and Hs-CRP levels were significantly higher in GG genotype subjects when compared to GC and CC. IL-18 was found to be interacting with 100 protein interactants. CONCLUSION:Our results indicate that Hs-CRP levels and IL-18-137(G/C) polymorphism may help to identify risk of future events of CAD in asymptomatic healthy FDRS.
Project description:Structural brain abnormalities and cognitive deficits have been reported in patients with schizophrenia and to a lesser extent in their first-degree relatives (FDRs). Here we investigated whether brain abnormalities in nonpsychotic relatives differ per type of FDR and how these abnormalities are related to intelligent quotient (IQ). Nine hundred eighty individuals from 5 schizophrenia family cohorts (330 FDRs, 432 controls, 218 patients) were included. Effect sizes were calculated to compare brain measures of FDRs and patients with controls, and between each type of FDR. Analyses were repeated with a correction for IQ, having a nonpsychotic diagnosis, and intracranial volume (ICV). FDRs had significantly smaller ICV, surface area, total brain, cortical gray matter, cerebral white matter, cerebellar gray and white matter, thalamus, putamen, amygdala, and accumbens volumes as compared with controls (ds < -0.19, q < 0.05 corrected). Offspring showed the largest effect sizes relative to the other FDRs; however, none of the effects in the different relative types survived correction for multiple comparisons. After IQ correction, all effects disappeared in the FDRs after correction for multiple comparisons. The findings in FDRs were not explained by having a nonpsychotic disorder and were only partly explained by ICV. FDRs show brain abnormalities that are strongly covarying with IQ. On the basis of consistent evidence of genetic overlap between schizophrenia, IQ, and brain measures, we suggest that the brain abnormalities in FDRs are at least partly explained by genes predisposing to both schizophrenia risk and IQ.
Project description:Melanoma survivors can play a pivotal role in raising family melanoma risk awareness, but are not always aware of family risk. This study examines patterns and sources of survivors' awareness that first-degree relatives (FDRs) face heightened melanoma risk.Population-based melanoma survivors (n = 170) completed a 15-min telephone interview. Logistic regressions examining covariates were conducted using awareness (yes vs no) of heightened risk to FDRs as the dependent variable.Almost half (41%) were unaware that their FDRs faced heightened melanoma risk. Of those 59% who were aware, most learned this from dermatologists. In multivariable analyses perceived risk and body site remained significant.Many melanoma survivors remain unaware that their FDRs are at melanoma risk. The results underscore the role that dermatologists and other doctors play in fostering risk awareness. Sensitivity to providing family risk information to survivors who have lower risk perceptions, regardless of anatomic site, is warranted.
Project description:Colorectal cancer (CRC) risk estimates based on family history typically include only close relatives. We report familial relative risk (FRR) in probands with various combinations, or constellations, of affected relatives, extending to third-degree.A population-based resource that includes a computerized genealogy linked to statewide cancer records was used to identify genetic relationships among CRC cases and their first-, second-, and third-degree relatives (FDRs, SDRs, and TDRs). FRRs were estimated by comparing the observed number of affected persons with a particular family history constellation to the expected number, based on cohort-specific CRC rates.A total of 2,327,327 persons included in > or =3 generation family histories were analyzed; 10,556 had a diagnosis of CRC. The FRR for CRC in persons with > or =1 affected FDR = 2.05 (95% CI, 1.96-2.14), consistent with published estimates. In the absence of a positive first-degree family history, considering both affected SDRs and TDRs, only 1 constellation had an FRR estimate that was significantly >1.0 (0 affected FDRs, 1 affected SDR, 2 affected TDRs; FRR = 1.33; 95% CI, 1.13-1.55). The FRR for persons with 1 affected FDR, 1 affected SDR, and 0 affected TDRs was 1.88 (95% CI, 1.59-2.20), increasing to FRR = 3.28 (95% CI, 2.44-4.31) for probands with 1 affected FDR, 1 affected SDR, and > or =3 affected TDRs.Increased numbers of affected FDRs influences risk much more than affected SDRs or TDRs. However, when combined with a positive first-degree family history, a positive second- and third-degree family history can significantly increase risk.
Project description:The genetic nature of an inherited cardiac condition (ICC) places first- and second-degree relatives at risk of cardiac complications and sudden death, even in the absence of symptoms. Communication of cardiac genetic risk information allows at-risk relatives to clarify, manage, and potentially prevent ICC-associated risks through cardiac screening. Literature regarding family communication of genetic risk information are predominantly based on Western populations, with limited insight into the Asian experience. This qualitative exploratory study provides a male perspective into the communication of ICC risks within families in Singapore. Eight male participants with clinically diagnosed cardiomyopathy, who had all received genetic counseling, were recruited. A phenomenological perspective was used to identify emergent themes from semi-structured interviews. In this study, most participants recalled their healthcare professional's emphasis on family communication. Notably, participants revealed that at-risk relatives were not accessing screening, and many described family members as currently asymptomatic and "healthy." These findings coincide with documented Asian beliefs regarding perceptions of health, which have important implications for the provision of genetic counseling support within Asian communities, especially in facilitating family communication such that at-risk relatives are informed about their ICC risks and available management options.
Project description:Atherosclerotic cardiovascular disease (ASCVD) is highly heritable, particularly when it occurs at a young age. The screening of individuals with premature ASCVD, although often recommended, is not routinely performed. Strategies to address this gap in care are essential. We designed the Study to Avoid CardioVascular Events in British Columbia (SAVE BC) as a prospective, observational study of individuals with a new diagnosis of very premature ASCVD (defined as age ≤ 50 years in males and age ≤ 55 years in females) and their first-degree relatives (FDRs) and spouses. FDRs and spouses will undergo screening for cardiovascular (CV) risk factors and subclinical ASCVD using a structured screening algorithm. All subjects will be followed longitudinally for ≥10 years. The overall goal of SAVE BC is to evaluate the yield of a structured screening program for identifying individuals at risk of premature ASCVD. The primary objectives of SAVE BC are to identify and follow index cases with very premature ASCVD and their FDRs and to determine the diagnostic yield of a structured screening program for these individuals. We will collect data on CV risk factors, medication use, CV events, and healthcare costs in these individuals. SAVE BC will provide insight regarding approaches to identify individuals at risk for premature ASCVD with implications for prevention and treatment in this population.