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BackgroundIn the clinical setting, identification of the genetic cause in patients with early-onset dementia (EOD) is challenging due to multiple types of genetic tests required to arrive at a diagnosis. Whole-genome sequencing (WGS) has the potential to serve as a single diagnostic platform, due to its superior ability to detect common, rare and structural genetic variation.MethodsWGS analysis was performed in 50 patients with EOD. Point mutations, small insertions/deletions, as well as structural variants (SVs) and short tandem repeats (STRs), were analysed. An Alzheimer’s disease (AD)-related polygenic risk score (PRS) was calculated in patients with AD.ResultsClinical genetic diagnosis was achieved in 7 of 50 (14%) of the patients, with a further 8 patients (16%) found to have established risk factors which may have contributed to their EOD. Two pathogenic variants were identified through SV analysis. No expanded STRs were found in this study cohort, but a blinded analysis with a positive control identified aC9orf72expansion accurately. Approximately 37% (7 of 19) of patients with AD had a PRS equivalent to >90th percentile risk.DiscussionWGS acts as a single genetic test to identify different types of clinically relevant genetic variations in patients with EOD. WGS, if used as a first-line clinical diagnostic test, has the potential to increase the diagnostic yield and reduce time to diagnosis for EOD.

PurposePopulation-based carrier screening for fragile X syndrome (FXS) is still not universally endorsed by professional organizations due to concerns around genetic counseling for complex information and potential for psychosocial harms.MethodsWe determined uptake levels, decision making, and psychosocial impact in a prospective study of pregnant and nonpregnant Australian women offered FXS carrier screening in clinical settings. Women received pretest genetic counseling, and completed questionnaires when deciding and one month later.ResultsOf 1,156 women recruited, 83.1% returned the first questionnaire with 70.6% nonpregnant and 58.8% pregnant women choosing testing (χ2=16.98, P

An audit was conducted of laboratory/clinical databases of genetic tests performed between January 2003 and December 2009, and for 2014, as well as referrals to the clinical service and a specialist multidisciplinary clinic, to determine genetic testing request patterns for fragile X syndrome and associated conditions and referrals for genetic counseling/multidisciplinary management in Victoria, Australia. An expanded allele (full mutation, premutation or intermediate) was found in 3.7% of tests. Pediatricians requested ∼70% of test samples, although fewer general practitioners and more obstetricians/gynecologists ordered tests in 2014. Median age at testing for individuals with a full mutation seeking a diagnosis without a fragile X family history was 4.3 years (males) and 9.4 years (females); these ages were lower when pediatricians ordered the tests (2.1 years and 6.1 years, respectively). Individuals with a premutation were generally tested at a later age (median age: males, 33.2 years; females, 36.4 years). Logistic regression showed that a family history of ID (OR 3.28 P = 0.005, CI 1.77-5.98) was the only indication to independently increase the likelihood of a test-positive (FM or PM) result. Following testing, ∼25% of full mutation or premutation individuals may not have attended clinical services providing genetic counseling or multidisciplinary management for these families. The apparent delay in fragile X syndrome diagnosis and lack of appropriate referrals for some may result in less than optimal management for these families. These findings suggest continued need for awareness and education of health professionals around diagnosis and familial implications of fragile X syndrome and associated conditions. © 2016 Wiley Periodicals, Inc.

Guided by the Consolidated Framework for Implementation Research (CFIR), this study aimed to identify factors that influence implementation of evidence-based provider and client-oriented strategies to promote colorectal cancer (CRC) screening in safety net health systems. Site visits and key informant interviews (n=33) were conducted with project leaders and staff in five health systems funded by an American Cancer Society grants program. Within- and cross-site analyses identified CFIR constructs that influenced implementation of provider and client-oriented strategies to promote CRC screening through colonoscopies and fecal immunochemical tests. Of the five CFIR domains, constructs within four CFIR domains (inner setting, outer setting, individual characteristics and process domains) were particularly salient in discussions of implementation while constructs within one CFIR domain (characteristics of the intervention) were not. This study provides a detailed description of how facilitating and inhibiting factors influenced the implementation of evidence-based practices related to CRC screening within safety net health systems. These findings can inform future efforts to promote evidence-based strategies to increase CRC screening rates in safety net health systems.

Implementing evidence-based practices (EBPs) to increase cancer screenings in safety net primary care systems has great potential for reducing cancer disparities. Yet there is a gap in understanding the factors and mechanisms that influence EBP implementation within these high-priority systems. Guided by the Consolidated Framework for Implementation Research (CFIR), our study aims to fill this gap with a multiple case study of health care safety net systems that were funded by an American Cancer Society (ACS) grants program to increase breast and colorectal cancer screening rates. The initiative funded 68 safety net systems to increase cancer screening through implementation of evidence-based provider and client-oriented strategies.Data are from a mixed-methods evaluation with nine purposively selected safety net systems. Fifty-two interviews were conducted with project leaders, implementers, and ACS staff. Funded safety net systems were categorized into high-, medium-, and low-performing cases based on the level of EBP implementation. Within- and cross-case analyses were performed to identify CFIR constructs that influenced level of EBP implementation.Of 39 CFIR constructs examined, six distinguished levels of implementation. Two constructs were from the intervention characteristics domain: adaptability and trialability. Three were from the inner setting domain: leadership engagement, tension for change, and access to information and knowledge. Engaging formally appointed internal implementation leaders, from the process domain, also distinguished level of implementation. No constructs from the outer setting or individual characteristics domain differentiated systems by level of implementation.Our study identified a number of influential CFIR constructs and illustrated how they impacted EBP implementation across a variety of safety net systems. Findings may inform future dissemination efforts of EBPs for increasing cancer screening in similar settings. Moreover, our analytic approach is similar to previous case studies using CFIR and hence could facilitate comparisons across studies.

Background: Medically underserved, uninsured patients experience individual and structural barriers to screening for breast and colon cancer, contributing to ongoing cancer health disparities. Community-based safety net clinics serving this patient population use a variety of policy and system-level strategies that can reduce patient barriers. A qualitative study conducted by The American Cancer Society (Society) and the Emory Prevention Research Center (EPRC) on safety net clinics highlights key patient barriers and strategies employed to overcome these barriers to increase cancer screening in this population. Methods: Society evaluators conducted site visits to nine safety net clinics receiving grant funds from the Society to increase breast and colon cancer screening among underserved populations in 2013. The evaluation assessed the implementation process of client and provider-directed intervention strategies. Evaluation staff conducted 52 in-depth interviews with 3-10 staff at each clinic. Interviews were digitally recorded and transcribed verbatim. Transcriptions were coded and analyzed by a team of researchers from both organizations using the Consolidated Framework for Implementation Research (CFIR) constructs to assess factors associated with effective implementation. Results: A majority of interviewees (67%-100%, mean 87%) in all 9 sites talked about patient needs and barriers and ways to address them. Patient barriers identified included low English proficiency, presenting challenges in communicating with providers; low health literacy; additional challenges to preparing for colonoscopies; limited transportation to services; lack of insurance/underinsurance; fear of cancer and co-morbidities that add to the complexity of the screening process. At the system level, structural barriers included perceived complexity of the healthcare system; requirement of multiple clinic visits to different locations to receive education and screening; and inconsistent messages received from providers at different facilities. While sites employed a variety of strategies to address patient barriers, almost all sites stressed that they are patient-centered and that the clinic staff prioritized improving patients' experience and meeting their needs. Some mentioned the importance of patient activation, ensuring the patients had all necessary information and were fully engaged in decisions about the screening process. One such respondent commented, “If we empower the patients with knowledge and give them the information up front and establish that accountability, then we'll see a reduction in lost patients.” Besides providing interpretation, transportation assistance, and assistance in getting insurance or other access to screening services, many sites utilized patient navigators to conduct education and patient reminders to promote cancer screening. Some sites implemented system-level changes to streamline the workflow of clinical processes to reduce the steps required of patients when accessing screening services. Respondents felt that system-level changes increased the likelihood of sustainable improvement in patient experiences, completion of screening, and the quality of preparation for screening. Conclusion: This presentation will describe in detail the strategies employed by safety net clinics and discuss potential approaches to strengthen safety nets' capacity in addressing patient barriers, which has great potential to further reduce cancer health disparities experienced by underserved and uninsured populations. Citation Format: Rentonia Morton, Megan Cotter, Kara Riehman, Lily Shuting Liang, Michelle Kegler, Emily Phillips, Derrick Beasley, April Hermstad, Jeremy Martinez. Addressing patient barriers to cancer screening in safety net clinics. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr B79.

Background Implementing evidence-based practices (EBPs) to increase cancer screenings in safety net primary care systems has great potential for reducing cancer disparities. Yet there is a gap in understanding the factors and mechanisms that influence EBP implementation within these high-priority systems. Guided by the Consolidated Framework for Implementation Research (CFIR), our study aims to fill this gap with a multiple case study of health care safety net systems that were funded by an American Cancer Society (ACS) grants program to increase breast and colorectal cancer screening rates. The initiative funded 68 safety net systems to increase cancer screening through implementation of evidence-based provider and client-oriented strategies. Methods Data are from a mixed-methods evaluation with nine purposively selected safety net systems. Fifty-two interviews were conducted with project leaders, implementers, and ACS staff. Funded safety net systems were categorized into high-, medium-, and low-performing cases based on the level of EBP implementation. Within- and cross-case analyses were performed to identify CFIR constructs that influenced level of EBP implementation. Results Of 39 CFIR constructs examined, six distinguished levels of implementation. Two constructs were from the intervention characteristics domain: adaptability and trialability. Three were from the inner setting domain: leadership engagement, tension for change, and access to information and knowledge. Engaging formally appointed internal implementation leaders, from the process domain, also distinguished level of implementation. No constructs from the outer setting or individual characteristics domain differentiated systems by level of implementation. Conclusions Our study identified a number of influential CFIR constructs and illustrated how they impacted EBP implementation across a variety of safety net systems. Findings may inform future dissemination efforts of EBPs for increasing cancer screening in similar settings. Moreover, our analytic approach is similar to previous case studies using CFIR and hence could facilitate comparisons across studies. Electronic supplementary material The online version of this article (doi:10.1186/s13012-016-0477-4) contains supplementary material, which is available to authorized users.