Charleshanson4740

OBJECTIVES Dissemination and implementation (D&I) science analyzes interventional strategies that aid in spreading scientific knowledge, adopting evidence into practice, and identifying barriers to maximize successful integration of science into practice. This study set out to critically appraise the published D&I strategies of the American Academy of Otolaryngology-Head and Neck Surgery Foundation (AAO-HNSF) Clinical Practice Guidelines (CPGs) and to introduce the theories of D&I science. METHODS The 15 AAO-HNSF CPGs underwent appraisal by 2 independent reviewers using the Appraisal of Guidelines for Research & Evaluation II (AGREE II) instrument. CPGs were rated over 23 key items in 6 domains. Each item was rated on a 7-point scale from 1 (strongly disagree) to 7 (strongly agree). CPGs were rated and quality assessments were performed. Intrarater reliability was assessed. RESULTS The overall mean score of the CPGs was 85.2% (95% confidence interval, 83.4%-86.9%). Individual CPG mean scores ranged from 80.4% to 90.9%. Mean interrater reliability was strong. All domains of the AGREE II instrument, except the Applicability domain, scored a mean of 90.7% or better. D&I strategies within the CPGs, as calculated by the Applicability domain score, ranged from 22.9% to 77.1%. DISCUSSION There is a paucity of published D&I strategies within the AAO-HNSF CPGs. Nesting a D&I framework, such as the Quality Improvement Framework, within CPGs would allow for identification of barriers to CPG adoption and evaluation of CPG-directed interventions. IMPLICATIONS FOR PRACTICE A D&I framework within the AAO-HNSF CPGs would allow for objective measurement of the overall impact of CPGs on otolaryngology practices.PURPOSE To determine the sensitivity and specificity of genetic testing criteria for the detection of germline pathogenic variants in women with breast cancer. MATERIALS AND METHODS Women with breast cancer enrolled in a breast cancer registry at a tertiary cancer center between 2000 and 2016 were evaluated for germline pathogenic variants in 9 breast cancer predisposition genes (ATM, BRCA1, BRCA2, CDH1, CHEK2, NF1, PALB2, PTEN, and TP53). The performance of the National Comprehensive Cancer Network (NCCN) hereditary cancer testing criteria was evaluated relative to testing of all women as recommended by the American Society of Breast Surgeons. RESULTS Of 3,907 women, 1,872 (47.9%) meeting NCCN criteria were more likely to carry a pathogenic variant in 9 predisposition genes compared with women not meeting criteria (9.0% v 3.5%; P 98% sensitivity for BRCA1 and BRCA2. CONCLUSION A substantial proportion of women with breast cancer carrying germline pathogenic variants in predisposition genes do not qualify for testing by NCCN criteria. Expansion of NCCN criteria to include all women diagnosed at ≤ 65 years of age improves the sensitivity of the selection criteria without requiring testing of all women with breast cancer.PURPOSE Primary endocrine therapy for ductal carcinoma in situ (DCIS) as a potential alternative to surgery has been understudied. This trial explored the feasibility of a short-term course of letrozole and sought to determine whether treatment results in measurable radiographic and biologic changes in estrogen receptor (ER)-positive DCIS. PATIENTS AND METHODS A phase II single-arm multicenter cooperative-group trial was conducted in postmenopausal patients diagnosed with ER-positive DCIS without invasion. Patients were treated with letrozole 2.5 mg per day for 6 months before surgery. Breast magnetic resonance imaging (MRI) was obtained at baseline, 3 months, and 6 months. The primary end point was change in 6-month MRI enhancement volume compared with baseline. RESULTS Overall, 79 patients were enrolled and 70 completed 6 months of letrozole. Of these, 67 patients had MRI data available for each timepoint. Baseline MRI volumes ranged from 0.004 to 26.3 cm3. Median reductions from baseline MRI volume (1.4 cm3) were 0.6 cm3 (61.0%) at 3 months (P less then .001) and 0.8 cm3 (71.7%) at 6 months (P less then .001). Consistent reductions were seen in median baseline ER H-score (228; median reduction, 15.0; P = .005), progesterone receptor H-score (15; median reduction, 85.0; P less then .001), and Ki67 score (12%; median reduction, 6.3%; P = .007). Of the 59 patients who underwent surgery per study protocol, persistent DCIS remained in 50 patients (85%), invasive cancer was detected in six patients (10%), and no residual DCIS or invasive cancer was seen in nine patients (15%). CONCLUSIONS In a cohort of postmenopausal women with ER-positive DCIS, preoperative letrozole resulted in significant imaging and biomarker changes. These findings support future trials of extended endocrine therapy as primary nonoperative treatment of some DCIS.Aim Before population screening of 'healthy' individuals is widely adopted, it is important to consider the harms and benefits of receiving positive results and how harms and benefits may differ by age. Subjects & methods Participants in a preventive genomic screening study were screened for 17 genes associated with 11 conditions. We interviewed 11 participants who received positive results. Results Interviewees expressed little concern about their positive results in light of their older age, the risk condition for which they tested positive, or other pressing health concerns. Conclusion Researchers and clinicians should recognize that returning positive results may not have the impact they presume given the diversity of the conditions screened and those who choose to undergo screening.Effective interventions and treatments for complex diseases have been implemented globally, however, coverage in Africa has been comparatively lower due to lack of capacity, clinical applicability and knowledge on the genetic contribution to disease and treatment. Currently, there is a scarcity of genetic data on African populations, which have enormous genetic diversity. Pharmacogenomics studies have the potential to revolutionise treatment of diseases, therefore, African populations are likely to benefit from these approaches to identify likely responders, reduce adverse side effects and optimise drug dosing. GSK2643943A cell line This review discusses clinical pharmacogenetics studies conducted in African populations, focusing on studies that examined drug response in complex diseases relevant to healthcare. Several pharmacogenetics associations have emerged from African studies, as have gaps in knowledge.