Recommended care and care adherence following a diagnosis of Lynch syndrome: a mixed-methods study.

BACKGROUND: Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome. This study assesses trends in diagnosis of LS and adherence to recommended LS-related care in a large integrated healthcare organization (~ 575,000 members). METHODS: Electronic medical record (EMR) data (1999-2015) were examined to identify patients with a diagnosis of LS. We examined their LS-associated care recommendations and adherence to these recommendations. Qualitative patient and provider interviews were conducted with the aim of identifying opportunities for improved care delivery. RESULTS: We identified 74 patients with a diagnosis of LS; 64% were diagnosed with a LS-related malignancy prior to their diagnosis of LS. The time to LS diagnosis following development of a LS-related cancer decreased over time: before 2009 11% of individuals received a diagnosis of LS within 1 year of developing a LS-related cancer compared to 83% after 2009 (p < 0.0001). Colonoscopy recommendations were documented in the EMR for almost all patients with LS (96%). Documentation of other recommendations for cancer surveillance was less commonly found. Overall, patient adherence to colonoscopy was high (M = 81.5%; SD = 32.7%), and adherence to other recommendations varied. To improve care coordination, patients and providers suggested providing automated reminder prompts for LS-related surveillance, adding a LS-specific diagnosis code, and providing guidelines for LS-related surveillance in the EMR. CONCLUSIONS: We identified fewer than expected patients with LS in our large care system, indicating that there is still a diagnostic care gap. However, patients with LS were likely to receive and follow CRC surveillance recommendations. Recommendations for and adherence to extracolonic surveillance were variable. Improved care coordination and clearer documentation of the LS diagnosis is needed.

Patient and provider perspectives on adherence to and care coordination of lynch syndrome surveillance recommendations: findings from qualitative interviews.

BACKGROUND: Patients with a genetic variant associated with Lynch syndrome (LS) are recommended to undergo frequent and repeated cancer surveillance activities to minimize cancer-related morbidity and mortality. Little is known about how patients and primary care providers (PCPs) track and manage these recommendations. We conducted a small exploratory study of patient and PCP experiences with recommended LS surveillance activities and communication with family members in an integrated health care system. METHODS: We used in-depth interviews with patients and providers to understand how surveillance is coordinated and monitored following confirmation of LS. We recruited patients with a range of ages/gender, and providers with at least at least one patient with a molecular diagnosis of LS. All interviews were recorded, transcribed, and content analyzed by a trained qualitative methodologist. RESULTS: Twenty-two interviews were completed with 12 patients and 10 providers. Most patients (10) had detailed knowledge of surveillance recommendations, but were less sure of time intervals. While all patients reported receiving initial education about their surveillance recommendations from a genetic counselor, seven did not follow-up with a genetic counselor in subsequent years. A third of patients described taking sole responsibility for managing their LS surveillance care. Lack of routine communication from the health system (e.g., prompts for surveillance activities), and provider engagement were surveillance barriers. PCPs were generally aware of LS, but had limited familiarity with surveillance recommendations. Most PCPs (7) viewed LS as rare and relied on patient and specialist expertise and support. Providers typically had 1 patient with LS in a panel of 1800 patients overall. Providers felt strongly that management of LS should be coordinated by a dedicated team of specialists. Most patients (92%) had at least one family member that sought LS testing, and common barriers for family members included lack of insurance, affordability, and fear of result. CONCLUSION: The maximal benefits of screening for confirmation of LS will only be realized with adherence to recommended preventive care. Important factors to ensure patients receive recommended LS care include a comprehensive and coordinated monitoring program that includes reminder prompts, and increased PCP education of LS and associated surveillance recommendations.

Universal tumor screening for Lynch syndrome: Assessment of the perspectives of patients with colorectal cancer regarding benefits and barriers.

BACKGROUND: Universal tumor screening for Lynch syndrome, the most common form of hereditary colorectal cancer (CRC), has been recommended among all patients newly diagnosed with CRC. However, there is limited literature regarding patient perspectives of tumor screening for Lynch syndrome among patients with CRC who are not selected for screening based on family history criteria. METHODS: A total of 145 patients aged 39 to 87 years were administered surveys assessing perceived risk, patient perspectives, and potential benefits of and barriers to tumor screening for Lynch syndrome. Associations between patient-specific and cancer-specific factors and survey responses were analyzed. RESULTS: The majority of participants perceived their risk of developing Lynch syndrome as being low, with 9 participants (6.2%) anticipating an abnormal screening result. However, most participants endorsed the potential benefits of screening for themselves and their families, with 84.8% endorsing ≥6 benefits and 50.3% endorsing all 8 benefits. Participants also endorsed few potential barriers to screening, with 89.4% endorsing ≤4 of 9 potential barriers. A common barrier was worry about the cost of additional testing and surveillance, which was endorsed by 54.5% of participants. The level of distress associated with tumor screening for Lynch syndrome, which was very low, was not associated with age or CRC stage. CONCLUSIONS: The results of the current study indicate that patients with CRC overall have a positive attitude toward tumor screening for Lynch syndrome, endorse the benefits of screening, and experience low levels of distress. These findings provide insight into patient attitudes toward tumor screening for Lynch syndrome among unselected patients with CRC to inform educational approaches that assist in patient decision-making and guide the successful implementation of screening programs.

Impact of family history assessment on communication with family members and health care providers: A report from the Family Healthware™ Impact Trial (FHITr).

OBJECTIVE: This study examines the impact of Family Healthware™ on communication behaviors; specifically, communication with family members and health care providers about family health history. METHODS: A total of 3786 participants were enrolled in the Family Healthware™ Impact Trial (FHITr) in the United States from 2005-7. The trial employed a two-arm cluster-randomized design, with primary care practices serving as the unit of randomization. Using generalized estimating equations (GEE), analyses focused on communication behaviors at 6month follow-up, adjusting for age, site and practice clustering. RESULTS: A significant interaction was observed between study arm and baseline communication status for the family communication outcomes (p's<.01), indicating that intervention had effects of different magnitude between those already communicating at baseline and those who were not. Among participants who were not communicating at baseline, intervention participants had higher odds of communicating with family members about family history risk (OR=1.24, p=0.042) and actively collecting family history information at follow-up (OR=2.67, p=0.026). Family Healthware™ did not have a significant effect on family communication among those already communicating at baseline, or on provider communication, regardless of baseline communication status. Greater communication was observed among those at increased familial risk for a greater number of diseases. CONCLUSION: Family Healthware™ prompted more communication about family history with family members, among those who were not previously communicating. Efforts are needed to identify approaches to encourage greater sharing of family history information, particularly with health care providers.

Clinical utility of family history for cancer screening and referral in primary care: a report from the Family Healthware Impact Trial.

PURPOSE: To assess the effectiveness of computerized familial risk assessment and tailored messages for identifying individuals for targeted cancer prevention strategies and motivating behavior change. METHODS: We conducted a randomized clinical trial in primary care patients aged 35-65 years using Family Healthware, a self-administered, internet-based tool that collects family history for six common diseases including breast cancer, colon cancer, and ovarian cancer, stratifies risk into three tiers, and provides tailored prevention messages. Cancer screening adherence and consultation were measured at baseline and 6-month follow-up. RESULTS: Of 3283 participants, 34% were at strong or moderate risk of at least one of the cancers. Family Healthware identified additional participants for whom earlier screening (colon cancer, 4.4%; breast cancer, women ages: 35-39 years, 9%) or genetic assessment (colon cancer, 2.5%; breast cancer, 10%; and ovarian cancer, 4%) may be indicated. Fewer than half were already adherent with risk-based screening. Screening adherence improved for all risk categories with no difference between intervention and control groups. Consultation with specialists did not differ between groups. CONCLUSION: Family Healthware identified patients for intensified cancer prevention. Engagement of clinicians and patients, integration with clinical decision support, and inclusion of nonfamilial risk factors may be necessary to achieve the full potential of computerized risk assessment.

Components of family history associated with women's disease perceptions for cancer: a report from the Family Healthware™ Impact Trial.

PURPOSE: To determine the specific components of family history and personal characteristics related to disease perceptions about breast, colon, and ovarian cancers. METHODS: Baseline, cross-sectional data on 2,505 healthy women aged 35-65 years enrolled from 41 primary care practices in the cluster-randomized Family Healthware™ Impact Trial, assessed for detailed family history and perceived risk, perceived severity, worry, and perceived control over getting six common diseases including breast, colon, and ovarian cancers. RESULTS: Participants provided family history information on 41,841 total relatives. We found evidence of underreporting of paternal family history and lower perceived breast cancer risk with cancer in the paternal versus maternal lineage. We observed cancer-specific perceived risks and worry for individual family history elements and also found novel "spillover" effects where a family history of one cancer was associated with altered disease perceptions of another. Having a mother with early-onset breast or ovarian cancer was strongly associated with perceived risk of breast cancer. Age, parenthood, and affected lineage were associated with disease perceptions and ran counter to empiric risks. CONCLUSIONS: Understanding patients' formulation of risk for multiple diseases is important for public health initiatives that seek to inform risk appraisal, influence disease perceptions, or match preventive interventions to existing risk perceptions.

Effect of preventive messages tailored to family history on health behaviors: the Family Healthware Impact Trial.

PURPOSE: We wanted to determine the impact of automated family history assessment and tailored messages for coronary heart disease, stroke, diabetes, colorectal, breast, and ovarian cancer on preventive behaviors compared with a standard preventive message. METHODS: The study was a cluster-randomized clinical trial that included 41 primary care practices, the majority in the Midwest, using Family Healthware, a self-administered, Web-based tool that assesses familial risk for the diseases and provides personalized risk-tailored messages. Patients in the control group received an age- and sex-specific health message related to lifestyle and screening. Smoking cessation, fruit and vegetable intake, physical activity, aspirin use, blood pressure, and cholesterol and blood glucose screening were assessed at baseline and 6 months after the intervention. RESULTS: Of 4,248 participants, 3,344 (78%) completed the study. Participants were white (91%), female (70%), and insured (97%), and had a mean age of 50.6 years (range 35-65 years). Intervention participants were more likely to increase daily fruit and vegetable consumption from 5 or fewer servings a day to 5 or more servings a day (OR = 1.29; 95% confidence interval [CI], 1.05-1.58) and to increase physical activity (OR = 1.47; 95% CI, 1.08-1.98) to 5 to 6 times a week for 30 minutes or more a week. The absolute differences in proportion were 3% and 4%, respectively. Intervention participants were less likely to move from not having cholesterol screening in the last 5 years to having their cholesterol measured within 5 years (OR = 0.34; 95% CI, 0.17-0.67), with an absolute difference of 15%. CONCLUSIONS: Messages tailored to an individual's familial risk for 6 common diseases modestly increased self-reported physical activity and fruit and vegetable intake but reduced the likelihood of receiving cholesterol screening.

Family history and perceptions about risk and prevention for chronic diseases in primary care: a report from the family healthware impact trial.

PURPOSE: To determine whether family medical history as a risk factor for six common diseases is related to patients' perceptions of risk, worry, and control over getting these diseases. METHODS: We used data from the cluster-randomized, controlled Family Healthware Impact Trial (FHITr). At baseline, healthy primary care patients reported their perceptions about coronary heart disease, stroke, diabetes, and breast, ovarian, and colon cancers. Immediately afterward, intervention group participants used Family Healthware to record family medical history; this web-based tool stratified familial disease risks. Multivariate and multilevel regression analyses measured the association between familial risk and patient perceptions for each disease, controlling for personal health and demographics. RESULTS: For the 2330 participants who used Family Healthware immediately after providing baseline data, perceived risk and worry for each disease were strongly associated with family history risk, adjusting for personal risk factors. The magnitude of the effect of family history on perceived risk ranged from 0.35 standard deviation for ovarian cancer to 1.12 standard deviations for colon cancer. Family history was not related to perceived control over developing diseases. Risk perceptions seemed optimistically biased, with 48-79% of participants with increased familial risk for diseases reporting that they were at average risk or below. CONCLUSIONS: Participants' ratings of their risk for developing common diseases, before feedback on familial risk, parallels but is often lower than their calculated risk based on family history. Having a family history of a disease increases its salience and does not change one's perceived ability to prevent the disease.

Association of common genetic variants in SMAD7 and risk of colon cancer.

Two recent genome-wide association studies (GWAS) identified three common variants in SMAD7 (rs4464148, rs4939827 and rs12953717) that confer modest susceptibility to colorectal cancer. Here, we replicated the association of rs4464148 with colon cancer in a population-based case-control study (561 cases and 721 controls). Compared with the TT genotype, those with CT and CC had an adjusted odds ratio (OR) and 95% confidence interval of 1.06 (0.82-1.38) and 1.86 (1.17-2.96), respectively (P(trend) = 0.04). However, stratified analyses revealed that this association was limited to women only [OR = 1.25 (0.88-1.78) for CT and OR = 2.76 (1.53-4.98) for CC, P(trend) = 0.002, P(interaction) = 0.08], which was not noted in any GWAS. Similarly, we found evidence for association with both rs4939827 and rs12953717 in women only (P = 0.007 in dominant rs4939827 model and P = 0.015 in recessive rs12953717 model), but not in men (P > 0.05) and evidence of an interaction with gender (P = 0.015 for rs4939827 and P = 0.061 for rs12953717). Similar effect modification was found in haplotype analyses. Our data add evidence supporting these genetic variants as markers predisposing to colon cancer, specifically in women.

Comparison of risk perceptions and beliefs across common chronic diseases.

OBJECTIVES: Few studies have compared perceptions of risk, worry, severity and control across multiple diseases. This paper examines how these perceptions vary for heart disease, diabetes, stroke, and colon, breast, and ovarian cancers. METHODS: The data for this study came from the Family Healthware Impact Trial (FHITr), conducted in the United States from 2005 to 2007. Healthy adults (N=2362) from primary care practices recorded their perceptions at baseline for each disease. Analyses were conducted controlling for study site and personal risk factors. RESULTS: Perceived risk was significantly higher for cancers than for other diseases. Men worried most about getting heart disease; women worried most about getting breast cancer, followed by heart disease. Diabetes was perceived to be the least severe condition. Heart disease was perceived to be the most controllable compared to cancers, which were perceived to be the least controllable. Women had higher perceived risk and worry ratings compared to men for several diseases. CONCLUSIONS: These data highlight how individuals comparatively view chronic diseases. Addressing prior disease perceptions when communicating multiple disease risks may facilitate an accurate understanding of risk for diseases, and help individuals to effectively identify and engage in relevant behaviors to reduce their risk.

Implementation of a Systematic Tumor Screening Program for Lynch Syndrome in an Integrated Health Care Setting.

A subset of colorectal cancer (CRC) cases are attributable to Lynch syndrome (LS), a hereditary form of CRC. Effective evaluation for LS can be done on CRC tumors to guide diagnostic testing. Increased diagnosis of LS allows for surveillance and risk reduction, which can mitigate CRC-related burden and prevent cancer-related deaths. We evaluated participation in LS screening among newly diagnosed adult CRC patients. Some cases were referred for genetics evaluation prior to study recruitment (selective screening). Those not referred directly were randomized to the intervention or control (usual care) arms. Control cases were observed for one year, then given information about LS screening. Patients who declined participation were followed through the medical record. Of 601 cases of CRC, 194 (32%) enrolled in our study and were offered LS screening, 43 (7%) were followed as a control group, 148 (25%) declined participation and 216 (36%) were ineligible [63 (10%) of which received prior selective screening]. Six and nine cases of LS were identified through the intervention and selective screening groups, respectively. Overall, a higher proportion of PMS2 variants were identified in the intervention (3/6, 50%) versus selective screening groups (2/9, 22%) (not statistically significant). Eighty-eight percent and 23% of intervention and control patients, respectively, received LS screening. No control patients were found to have LS. Systems-based approaches are needed to ensure we fully identify LS cases. The proportion of LS cases from this program was 4% of newly diagnosed cases of CRC, similar to other programs.

A common 8q24 variant and the risk of colon cancer: a population-based case-control study.

Three recent studies identified common variants on 8q24 that confer modestly increased susceptibility to colorectal cancer. Here, we replicate the association in a population-based case-control study of colon cancer, including 561 cases and 721 unrelated controls. The rs6983267 marker was significantly associated with colon cancer risk. Compared with those homozygous for the T allele, the heterozygous and homozygous carriers for the G allele had an age-adjusted odds ratio of 1.39 (95% confidence interval, 1.03-1.88) and 1.68 (95% confidence interval, 1.21-2.33), respectively. An additive model showed strong evidence for a gene-dose response relationship (P(trend) = 0.0022). The association remained statistically significant when restricted to Caucasians only (527 cases and 679 controls; P(trend) = 0.0056). Further adjustment for other known risk factors did not alter the results. Stratified analysis revealed no evidence for effect modification by family history of colorectal cancer, age, or gender. These data replicate the association identified from recent studies, providing additional evidence supporting the rs6983267 genetic polymorphism as a marker predisposing to colon cancer.

New knowledge for and about primary care: a view through the looking glass of the Annals of Family Medicine.

PURPOSE: At this second anniversary of the Annals of Family Medicine, we sought to characterize primary care research and to identify opportunities for new directions by analyzing the content of the first and second volumes of the Annals. METHODS: Using an a priori classification scheme, 2 editors independently categorized each research article and essay published in 2003 and 2004, excluding supplements. We categorized the domain of knowledge, methods, topical content, whether articles represented core values of primary care, and looked for articles that studied health/illness/symptoms from a uniquely primary care experience. We reconciled differences by discussion. RESULTS: Among 110 articles, knowledge domains reflected the 4 quadrants of the clinician (n = 6), patient, family, or community (10), health care system (32), disease (22), or the interface (39) between these quadrants. The most frequent methods were cross-sectional studies (23), cohorts (15), randomized clinical trials (13), qualitative interviews (11), analyses of secondary data (11), systematic reviews (11), methods/theory development (10), self-reflections (8), and mixed methods (5). The most common topical areas were chronic disease and prevention. Core primary care values were represented in 75% of articles. Only 2 articles represented an integrative illness/healing perspective. CONCLUSIONS: Despite contemporary forces driving a reductionistic approach, primary care research, as reflected by articles published in the Annals of Family Medicine, addresses the domains of knowledge that contribute to comprehensive, relationship-centered health care. More work is needed to understand the nature of health and illness in whole people and ways to integrate diverse knowledge, methods and fragmented health care.

Current and future applications of genetics in primary care medicine.

Individualized medical treatment and prevention based on one's genetic makeup are promises likely to be fulfilled over decades. Already family history is taking a more prominent role in preventive care. Primary care clinicians and geneticists will increasingly collaborate to diagnose and manage genetic conditions: both single-gene disorders and multifactorial diseases such as infections,cancers, cardiovascular disease and mental illness. This will require society, with primary care clinicians in the forefront, to implement means for efficient family history-taking; maintaining private, personally accessible genetic health records; safeguarding people from genetic discrimination; distributing access to scarce genetic specialists and expensive technologies; rectifying lay misconceptions about inheritance; managing emotional responses and family dynamics related to genetic diagnosis; and motivating people at increased familial risk to take preventive action.

Cancer genetics in primary care.

The cloning of two major breast cancer susceptibility genes, BRCA1 and BRCA2, in 1994 and 1995 and the subsequent development of commercial genetic testing has brought hereditary cancer genetics into the public eye. In addition to DNA-based genetic testing, new strategies and treatments have been developed to provide accurate assessment of cancer risk and to reduce the chances of cancer developing in the future. This increasing scientific and public attention has prompted some cancer patients and their families to find out whether they "have the cancer gene" and has placed more responsibility on primary care clinicians to identify people who should be referred for specialized services of hereditary cancer genetics.

Clinical consult: developmental delay/fragile X syndrome.

Fragile X syndrome is an X-linked disorder characterized primarily by speech delay and moderate mental retardation. The incidence of fragile X syndrome is estimated at 1/4000-1/6000 males and half that for females. This article presents a case study of fragile X syndrome, describing the genetics and inheritance, disease characteristics,natural history, diagnosis, differential diagnosis, and management.

Clinical consult: Marfan syndrome.

Marfan syndrome is a heritable disorder of connective tissue. This relatively common genetic condition affects approximately 2 to 3 per 10,000 individuals, without a particular gender, racial, geographic,or ethnic predilection. If unrecognized, patients with Marfan syndrome can have life-threatening cardiovascular complications. Identification and proper management of the disorder can improve the prognosis greatly, however, and extend the patient's life span. This article presents a case study of Marfan syndrome, describing disease characteristics and natural history, inheritance and genetics, diagnosis,differential diagnosis, and management.

Clinical consult: iron overload--hereditary hemochromatosis.

One of the most common genetic causes of iron overload is hereditary hemochromatosis (HHC), a condition characterized by overabsorption of dietary iron from the gastrointestinal tract. This condition can lead to excessive iron accumulation with resulting dysfunction in multiple organs, including the liver, skin, heart,joints, pancreas, and testes. The clinical consequences of HHC if undetected and untreated can be severe and include liver cirrhosis,hepatocellular carcinoma, diabetes mellitus, cardiac arrhythmias and failure, arthritis, and hypogonadism. HHC is one of the most common heritable conditions in white populations of Northern European origin. This article presents a case study of HHC, describing inheritance and genetics, disease characteristics and natural history, diagnosis, differential diagnosis, and management.