Family health history is a leading predictor of disease risk. Nonetheless, it is underutilized to guide care and, therefore, is ripe for health information technology intervention. To fill the family health history practice gap, Cleveland Clinic has developed a family health history collection and clinical decision support tool, MyFamily. This report describes the impact and process of implementing MyFamily into primary care, cancer survivorship and cancer genetics clinics. Ten providers participated in semi-structured interviews that were analyzed to identify opportunities for process improvement. Participants universally noted positive effects on patient care, including increases in quality, personalization of care and patient engagement. The impact on clinical workflow varied by practice setting, with differences observed in the ease of integration and the use of specific report elements. Tension between the length of the report and desired detail was appreciated. Barriers and facilitators to the process of implementation were noted, dominated by the theme of increased integration with the electronic medical record. These results fed real-time improvement cycles to reinforce clinician use. This model will be applied in future institutional efforts to integrate clinical genomic applications into practice and may be useful for other institutions considering the implementation of tools for personalizing medical management.

Doctoral Fellow 1 | Kaitlyn Jones BSN, RN, Doctorate of Nursing Practice Student 1 | Brenda Rocha BSN, RN, CCRN, Doctorate of Nursing Practice Student 1 | Megan Doerr MS, LGC, Principal Scientist, Governance 2 | Emily Gabitzsch MS, LGC, Genetic Counselor 2 | Thad Meese BBA, MBA, Innovation Manager 2This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. AbstractBackground: A positive family history of type 2 diabetes (T2D) has been associated with risk awareness and risk-reducing behaviours among the unaffected relatives.Yet, little is known about how people with a positive family history for diabetes develop and manage their personal sense of risk.Objective: To characterize two key concepts, salience and vulnerability, within the familial risk perception (FRP) model among unaffected individuals, at increased familial risk for T2D. Design:We conducted a mixed method study. Descriptions of salience and vulnerability were collected through semi-structured interviews. Participant's perception of self-reported risk factors (family history, age, race/ethnicity, medical history, weight and exercise) was measured using the Perceived Risk Factors for T2D Tool and was compared to a clinical evaluation of the same risk factors. Results:We identified two components of salience: (a) concern for developing T2D and (b) risk awareness triggers, and two features of vulnerability: (a) statement of risk and (b) risk assessment devices. Although few participants (26%) were concordant between their perceived and clinical overall T2D risk, concordance for individual risk factors was higher, ranging from 42% (medical history) to 90% (family history). Discussion and conclusion:Both familial and non-familial events lead people to contemplate their T2D risk, even among people who have a positive family history.Participants often downplayed their overall risk and underestimated their overall risk compared to a clinical risk assessment of the same self-reported risk factors.Clinicians could leverage key components of the FRP process as way to engage patients in risk reduction strategies earlier. K E Y W O R D Smixed methods, risk perception, risk personalization process, salience, type 2 diabetes, vulnerability

Tuberous sclerosis complex (TSC) is an autosomal-dominant tumor-suppressor disorder characterized by the development of hamartomas in many organ systems. The prevalence of TSC is estimated at 1 in 6,000 individuals, and up to 70% of cases are due to de novo mutation. 1,2 Inactivating mutations in either the TSC1 or TSC2 gene, which encode the proteins hamartin and tuberin, respectively, cause TSC. 3,4 These proteins form a heterodimer involved in negative regulation of the mammalian target of rapamycin complex 1 (mTORC1) kinase. 5-7 mTORC1 is an important element in controlling cell proliferation and growth, insulin signaling, and protein translation. 8 Dysregulation of mTORC1 is an important aspect in the pathogenesis of TSC. 9 Somatic mutation of the second TSC1 or TSC2 allele leads to a loss of heterozygosity, upregulation of mTOR, and dysregulated cellular metabolism. 9 Although virtually any organ can be affected in TSC, the brain, skin, kidneys, heart, and lungs are the principal sites of pathology. TSC shows no ethnic or sex predilection, but interestingly, sex-specific manifestations have been described. Almost 40% of women with TSC develop the pulmonary manifestation lymphangioleiomyomatosis, typically between the ages of 20 and 40 years; most men are unaffected. 10,11 Moreover, the most common renal manifestation, angiomyolipoma, impacts more than 70% of patients, 2 but females are affected an estimated three to four times more often than males. 12 Lymphangioleiomyomatosis and angiomyolipomas share histological features and express estrogen and progesterone receptors, considered important in development. 13 Other effects of sex hormones or reproductive manifestations in TSC are poorly understood.Intriguingly, the role of the TSC1 and TSC2 genes in normal organ function and TSC-associated pathogenesis came to light from the creation of a variety of organ-specific Tsc1-or Tsc2-null animals. Recently, the use of conditional knockout models revealed a role for the murine Tsc1 and Tsc2 genes in the reproductive functioning of the ovary. 14,15 Specifically, these genes are crucial for the maintenance of primordial follicles in a quiescent state and appropriate activation throughout the murine reproductive period. Deletions of either the Tsc1 or Tsc2 gene in the ovaries of mice led to a premature activation of primordial follicles and subsequent depletion of the entire follicular pool, despite initial intact reproductive maturation. The mice essentially experienced what would be defined in humans as premature ovarian insufficiency (POI). POI represents a clear disruption in the normal female reproductive life span and is defined as the cessation of menses in a woman younger than 40 years. POI affects an estimated 1% of the females in the US Purpose: Little is known about sex-specific manifestations of tuberous sclerosis complex. Inactivating mutations in the TSC1 and TSC2 genes cause tuberous sclerosis complex, and recent evidence points to a crucial role for these genes in maintaining appropriate ovarian fun...