Purpose Family history of cancer (CFH) is important for identifying individuals to receive genetic counseling/testing (GC/GT). Prior studies have demonstrated low rates of family history documentation and referral for GC/GT. Methods CFH quality and GC/GT practices for patients with breast (BC) or colon cancer (CRC) were assessed in 271 practices participating in the American Society of Clinical Oncology Quality Oncology Practice Initiative in fall 2011. Results A total of 212 practices completed measures regarding CFH and GC/GT practices for 10,466 patients; 77.4% of all medical records reviewed documented presence or absence of CFH in first-degree relatives, and 61.5% of medical records documented presence or absence of CFH in second-degree relatives, with significantly higher documentation for patients with BC compared with CRC. Age at diagnosis was documented for all relatives with cancer in 30.7% of medical records (BC, 45.2%; CRC, 35.4%; P ≤ .001). Referall for GC/GT occurred in 22.1% of all patients with BC or CRC. Of patients with increased risk for hereditary cancer, 52.2% of patients with BC and 26.4% of those with CRC were referred for GC/GT. When genetic testing was performed, consent was documented 77.7% of the time, and discussion of results was documented 78.8% of the time. Conclusion We identified low rates of complete CFH documentation and low rates of referral for those with BC or CRC meeting guidelines for referral among US oncologists. Documentation and referral were greater for patients with BC compared with CRC. Education and support regarding the importance of accurate CFH and the benefits of proactive high-risk patient management are clearly needed.
The HEALTHY study was a multi-site randomized trial designed to determine whether a 3-year school-based intervention targeting nutrition and physical activity behaviors could effectively reduce risk factors associated with type 2 diabetes in middle school children. Pilot and formative studies were conducted to inform the development of the intervention components and the process evaluation methods for the main trial. During the main trial, both qualitative and quantitative assessments monitored the fidelity of the intervention and motivated modifications to improve intervention delivery. Structured observations of physical education classes, total school food environments, classroom-based educational modules, and communications and promotional campaigns provided verification that the intervention was delivered as intended. Interviews and focus groups yielded a multidimensional assessment of how the intervention was delivered and received, as well as identifying the barriers to and facilitators of the intervention across and within participating schools. Interim summaries of process evaluation data were presented to the study group as a means of ensuring standardization and quality of the intervention across the seven participating centers. Process evaluation methods and procedures documented the fidelity with which the HEALTHY study was implemented across 21 intervention schools and identified ways in which the intervention delivery might be enhanced throughout the study.
The Hippo signaling pathway regulates organ size and plays critical roles in maintaining tissue growth, homeostasis, and regeneration. Dysregulated in a wide spectrum of cancers, in mammals, this pathway is regulated by two key effectors, YAP and TAZ, that may functionally overlap. We found that TAZ promoted liver inflammation and tumor development. The expression of TAZ, but not YAP, in human liver tumors positively correlated with the expression of proinflammatory cytokines. Hyperactivated TAZ induced substantial myeloid cell infiltration into the liver and the secretion of proinflammatory cytokines through a TEAD-dependent mechanism. Furthermore, tumors with hyperactivated YAP and TAZ had distinct transcriptional signatures, which included the increased expression of inflammatory cytokines in TAZ-driven tumors. Our study elucidated a previously uncharacterized link between TAZ activity and inflammatory responses that influence tumor development in the liver.
Background TODAY (Treatment Options for type 2 Diabetes in Adolescents and Youth) is a federally-funded multi-center randomized clinical trial comparing three treatments of youth-onset type 2 diabetes. Objective To describe the experience of youth participating in a 2–6 month run-in period in preparation for randomization into TODAY. Subjects An ethnically diverse sample of 927 youth, 65.4% female, aged 13.7±2.0 years old, with type 2 diabetes for a median of 2 months (0.7–7.8 months, 25th-75th percentiles). Methods A run-in period was conducted to achieve HbA1c <8% with metformin monotherapy and diabetes education, and to evaluate adherence to pill taking, visit attendance, and other procedures. Results At entry, mean BMI and z-BMI were 35.6±7.7 and 2.3±0.4, respectively, mean HbA1c was 7.7±2.2%, only 42.5% were on a hypoglycemic treatment, and 35.6% had HbA1c ≥8%. Co-morbid conditions were common; 18.8% had hypertension, 24.2% had elevated cholesterol, and 6.5% had abnormal liver enzymes. After a median 71 days of run-in, 90.9% had HbA1c <8%, 77.9% had HbA1c <7%, and 46.4% had HbA1c <6%. Of the 772 youth achieving the target HbA1c <8%, 704 (91.2%) were randomized; non-adherence to metformin treatment was the main cause for non-randomization. Youth proceeding to randomization decreased weight by 0.68 kg and HbA1c by 1.45% compared to a weight gain of 0.71 kg and HbA1c decrease of 0.74% in the non-randomized youth (p=0.01 in both cases). Change in z-BMI was not significantly different between the two groups, however. Conclusions Most youth with recent onset type 2 diabetes can achieve target HbA1c <8.0% with short-term metformin monotherapy and standard diabetes education.
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