RESUMO
OBJECTIVE: We evaluated whether people who had not completed a faecal immunochemical test (FIT) for colorectal cancer (CRC) screening would complete a blood-based testing option if offered one during health encounters. Blood-based screening tests for CRC could add to the total number of people screened for CRC by providing another testing alternative. DESIGN: Study participants were patients aged 45-75 years at a large, integrated health system who were offered but did not complete an FIT in the prior 3-9 months and were scheduled for a clinical encounter. Individuals were randomised (1:1) to be offered a commercially available CRC blood test (Shield, Guardant Health) versus usual care. We compared 3-month CRC screening proportions in the two groups. RESULTS: We randomised 2026 patients; 2004 remained eligible following postrandomisation exclusions (1003 to usual care and 1001 to blood draw offer; mean age: 60, 62% female, 80% non-Hispanic white). Of the 1001 allocated to the blood test group, 924 were recruited following chart-review exclusions; 548 (59.3%) were reached via phone, of which 280 (51.1%) scheduled an appointment with the research team. CRC screening proportions were 17.5 percentage points higher in the blood test group versus usual care (30.5% vs 13.0%; OR 2.94, 95% CI 2.34 to 3.70; p<0.001). CONCLUSION: Among adults who had declined prior CRC screening, the offer of a blood-based screening test boosted CRC screening by 17.5 percentage points over usual care. Further research is needed on how to balance the favourable adherence with lower advanced adenoma detection compared with other available tests. TRIAL REGISTRATION NUMBER: NCT05987709.
Assuntos
Neoplasias Colorretais , Prestação Integrada de Cuidados de Saúde , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Detecção Precoce de Câncer , Colonoscopia , Sangue Oculto , Programas de Rastreamento , Neoplasias Colorretais/diagnóstico , Cooperação do PacienteRESUMO
PURPOSE: The ClinGen Actionability Working Group (AWG) developed an evidence-based framework to generate actionability reports and scores of gene-condition pairs in the context of secondary findings from genome sequencing. Here we describe the expansion of the framework to include actionability assertions. METHODS: Initial development of the actionability rubric was based on previously scored adult gene-condition pairs and individual expert evaluation. Rubric refinement was iterative and based on evaluation, feedback, and discussion. The final rubric was pragmatically evaluated via integration into actionability assessments for 27 gene-condition pairs. RESULTS: The resulting rubric has a 4-point scale (limited, moderate, strong, and definitive) and uses the highest-scoring outcome-intervention pair of each gene-condition pair to generate a preliminary assertion. During AWG discussions, predefined criteria and factors guide discussion to produce a consensus assertion for a gene-condition pair, which may differ from the preliminary assertion. The AWG has retrospectively generated assertions for all previously scored gene-condition pairs and are prospectively asserting on gene-condition pairs under assessment, having completed over 170 adult and 188 pediatric gene-condition pairs. CONCLUSION: The AWG expanded its framework to provide actionability assertions to enhance the clinical value of their resources and increase their utility as decision aids regarding return of secondary findings.
Assuntos
Medicina Baseada em Evidências , Humanos , Medicina Baseada em Evidências/métodos , Testes Genéticos/métodos , Achados Incidentais , Sequenciamento Completo do GenomaRESUMO
PURPOSE: The Risk of Pediatric and Adolescent Cancer Associated with Medical Imaging (RIC) Study is quantifying the association between cumulative radiation exposure from fetal and/or childhood medical imaging and subsequent cancer risk. This manuscript describes the study cohorts and research methods. METHODS: The RIC Study is a longitudinal study of children in two retrospective cohorts from 6 U.S. healthcare systems and from Ontario, Canada over the period 1995-2017. The fetal-exposure cohort includes children whose mothers were enrolled in the healthcare system during their entire pregnancy and followed to age 20. The childhood-exposure cohort includes children born into the system and followed while continuously enrolled. Imaging utilization was determined using administrative data. Computed tomography (CT) parameters were collected to estimate individualized patient organ dosimetry. Organ dose libraries for average exposures were constructed for radiography, fluoroscopy, and angiography, while diagnostic radiopharmaceutical biokinetic models were applied to estimate organ doses received in nuclear medicine procedures. Cancers were ascertained from local and state/provincial cancer registry linkages. RESULTS: The fetal-exposure cohort includes 3,474,000 children among whom 6,606 cancers (2394 leukemias) were diagnosed over 37,659,582 person-years; 0.5% had in utero exposure to CT, 4.0% radiography, 0.5% fluoroscopy, 0.04% angiography, 0.2% nuclear medicine. The childhood-exposure cohort includes 3,724,632 children in whom 6,358 cancers (2,372 leukemias) were diagnosed over 36,190,027 person-years; 5.9% were exposed to CT, 61.1% radiography, 6.0% fluoroscopy, 0.4% angiography, 1.5% nuclear medicine. CONCLUSION: The RIC Study is poised to be the largest study addressing risk of childhood and adolescent cancer associated with ionizing radiation from medical imaging, estimated with individualized patient organ dosimetry.
Assuntos
Leucemia , Adolescente , Adulto , Criança , Feminino , Humanos , Estudos Longitudinais , Ontário/epidemiologia , Gravidez , Radiografia , Estudos Retrospectivos , Adulto JovemRESUMO
PURPOSE: This study aimed to evaluate the laboratory-related outcomes of participants who were offered genomic testing based on cancer family history risk assessment tools. METHODS: Patients from clinics that serve populations with access barriers, who are screened at risk for a hereditary cancer syndrome based on adapted family history collection tools (the Breast Cancer Genetics Referral Screening Tool and PREMM5), were offered exome-based panel testing for cancer risk and medically actionable secondary findings. We used descriptive statistics, electronic health record review, and inferential statistics to explore participant characteristics and results, consultations and actions related to pathogenic/likely pathogenic variants identified, and variables predicting category of findings, respectively. RESULTS: Of all the participants, 87% successfully returned a saliva kit. Overall, 5% had a pathogenic/likely pathogenic cancer risk variant and 1% had a secondary finding. Almost all (14/15, 93%) participants completed recommended consultations with nongenetics providers after an average of 17 months. The recommended actions (eg, breast magnetic resonance imaging) were completed by 17 of 25 participants. Participant personal history of cancer and PREMM5 score were each associated with the category of findings (history and colon cancer finding, Fisher's exact P = .02; history and breast cancer finding, Fisher's exact P = .01; PREMM5TM score; and colon cancer finding, Fisher's exact P < .001). CONCLUSION: This accessible model of hereditary cancer risk assessment and genetic testing yielded results that were often acted upon by patients and physicians.
Assuntos
Neoplasias da Mama , Neoplasias do Colo , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Neoplasias do Colo/genética , Feminino , Predisposição Genética para Doença , Testes Genéticos/métodos , Humanos , Medição de RiscoRESUMO
PURPOSE: Synthesis and curation of evidence regarding the clinical actionability of secondary findings (SFs) from genome-scale sequencing are needed to support decision-making on reporting of these findings. To assess actionability of SFs in children and adolescents, the Clinical Genome Resource established the Pediatric Actionability Working Group (AWG). METHODS: The Pediatric AWG modified the framework of the existing Adult AWG, which included production of summary reports of actionability for genes and associated conditions and consensus actionability scores for specific outcome-intervention pairs. Modification of the adult framework for the pediatric setting included accounting for special considerations for reporting presymptomatic or predictive genetic findings in the pediatric context, such as maintaining future autonomy by not disclosing conditions not actionable until adulthood. The Pediatric AWG then applied this new framework to genes and associated conditions with putative actionability. RESULTS: As of September 2021, the Pediatric AWG applied the new framework to 70 actionability topics representing 143 genes. Reports and scores are publicly available at www.clinicalgenome.org. CONCLUSION: The Pediatric AWG continues to curate gene-condition topics and build an evidence-based resource, supporting clinical communities and decision-makers with policy development on the return of SFs in pediatric populations.
Assuntos
Testes Genéticos , Relatório de Pesquisa , Adolescente , Adulto , Criança , Mapeamento Cromossômico , HumanosRESUMO
Large research teams and consortia present challenges for authorship. The number of disciplines involved in the research can further complicate approaches to manuscript development and leadership. The CHARM team, representing a multi-disciplinary, multi-institutional genomics implementation study, participated in facilitated discussions inspired by team science methodologies. The discussions were centered on team members' past experiences with authorship and perspectives on authorship in a large research team context. Team members identified challenges and opportunities that were used to create guidelines and administrative tools to support manuscript development. The guidelines were organized by the three values of equity, inclusion, and efficiency and included eight principles. A visual dashboard was created to allow all team members to see who was leading or involved in each paper. Additional tools to promote equity, inclusion, and efficiency included providing standardized project management for each manuscript and making "concept sheets" for each manuscript accessible to all team members. The process used in CHARM can be used by other large research teams and consortia to equitably distribute lead authorship opportunities, foster coauthor inclusion, and efficiently work with large authorship groups.
RESUMO
PURPOSE: A major challenge in ductal carcinoma in situ (DCIS) treatment is selection of the most appropriate therapeutic approach for individual patients. We conducted an external prospective-retrospective clinical validation of a DCIS biologic risk signature, DCISionRT, in a population-based observational cohort of women diagnosed with DCIS and treated with breast-conserving surgery (BCS). EXPERIMENTAL DESIGN: Participants were 455 health plan members of Kaiser Permanente Northwest diagnosed with DCIS and treated with BCS with or without radiotherapy from 1990 to 2007. The biologic signature combined seven protein tumor markers assessed in formalin-fixed, paraffin-embedded tumor tissue with four clinicopathologic factors to provide a DCISionRT test result, termed decision score (DS). Cox regression and Kaplan-Meier analysis were used to measure the association of the DS, continuous (linear) or categorical (DS ≤ 3 vs. DS > 3), and subsequent total ipsilateral breast events and invasive ipsilateral breast events at least 6 months after initial surgery. RESULTS: In Cox regression, the continuous and categorical DS variables were positively associated with total and invasive breast event risk after adjustment for radiotherapy. In a subset analysis by treatment group, categorical Kaplan-Meier analyses showed at least 2-fold differences in 10-year risk of total breast events between the elevated-risk and low-risk DS categories. CONCLUSIONS: In this first external validation study of the DCISionRT test, the DS was prognostic for the risk of later breast events for women diagnosed with DCIS, following BCS.
Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/terapia , Carcinoma Intraductal não Infiltrante/terapia , Mastectomia Segmentar , Recidiva Local de Neoplasia/epidemiologia , Idoso , Mama/patologia , Mama/efeitos da radiação , Mama/cirurgia , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Tomada de Decisão Clínica/métodos , Técnicas de Apoio para a Decisão , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Prognóstico , Estudos Prospectivos , Radioterapia Adjuvante/estatística & dados numéricos , Estudos Retrospectivos , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND: Women who carry an FMR1 premutation (PM) allele and are mothers of children with fragile X syndrome (FXS) experience elevated maternal stress. In-person mindfulness sessions have been shown to be effective in alleviating maternal stress-related outcomes among mothers of children with intellectual and developmental disabilities. Our prior studies indicate women with a PM are at risk of social anxiety, a potential barrier to in-person mindfulness sessions. AIM: The main goals of this pilot study were to assess feasibility and adherence of an app-based mindfulness training program among mothers of children with FXS and to explore stress, social outcomes, and potential barriers to social support. METHODS: Participants (n = 18) completed questionnaires to assess stress and social anxiety, an app-based mindfulness program, and a semi-structured follow-up interview. RESULTS: Thirteen out of 18 (72%) participants completed the mindfulness program; of those, 10 (77%) found it helpful. Eight out of 18 (44%) participants met criteria for social anxiety and 11 (61%) reported having difficulties reaching out for help when needed. Women with social anxiety and those experiencing barriers to social support were more likely to find the program helpful. CONCLUSIONS: This study provides guidance for future mindfulness-based interventions to alleviate maternal stress in mothers of children with FXS.