Explore the vast range of titles available.

About 1% of non–small-cell lung cancers have ROS1 rearrangements. This oncogene is inhibited by crizotinib. In a cohort of 50 patients with ROS1 -rearranged lung cancer, crizotinib induced responses in 72%; the median duration of response was nearly a year and a half. The ROS1 oncogene encodes an orphan receptor tyrosine kinase related to anaplastic lymphoma kinase (ALK), along with members of the insulin-receptor family. 1 First discovered as the oncogene product of an avian sarcoma RNA tumor virus, 2 – 4 ROS1 (ROS1 proto-oncogene receptor tyrosine kinase) is activated by chromosomal rearrangement in a variety of human cancers, including non–small-cell lung cancer (NSCLC), cholangiocarcinoma, gastric cancer, ovarian cancer, and glioblastoma multiforme. 5 – 9 Rearrangement leads to fusion of a portion of ROS1 that includes the entire tyrosine kinase domain with 1 of 12 different partner proteins. 10 The resulting ROS1 fusion kinases are constitutively activated and drive . . .

ALK fusion genes occur in a subset of non-small-cell lung cancers (NSCLCs). We assessed the tolerability and activity of crizotinib in patients with NSCLC who were prospectively identified to have an ALK fusion within the first-in-man phase 1 crizotinib study. In this phase 1 study, patients with ALK-positive stage III or IV NSCLC received oral crizotinib 250 mg twice daily in 28-day cycles. Endpoints included tumour responses, duration of response, time to tumour response, progression-free survival (PFS), overall survival at 6 and 12 months, and determination of the safety and tolerability and characterisation of the plasma pharmacokinetic profile of crizotinib after oral administration. Responses were analysed in evaluable patients and PFS and safety were analysed in all patients. This study is registered with ClinicalTrials.gov, number NCT00585195. Between Aug 27, 2008, and June 1, 2011, 149 ALK-positive patients were enrolled, 143 of whom were included in the response-evaluable population. 87 of 143 patients had an objective response (60·8%, 95% CI 52·3–68·9), including three complete responses and 84 partial responses. Median time to first documented objective response was 7·9 weeks (range 2·1–39·6) and median duration of response was 49·1 weeks (95% CI 39·3–75·4). The response rate seemed to be largely independent of age, sex, performance status, or line of treatment. Median PFS was 9·7 months (95% CI 7·7–12·8). Median overall survival data are not yet mature, but estimated overall survival at 6 and 12 months was 87·9% (95% CI 81·3–92·3) and 74·8% (66·4–81·5), respectively. 39 patients continued to receive crizotinib for more than 2 weeks after progression because of perceived ongoing clinical benefit from the drug (12 for at least 6 months from the time of their initial investigator-defined disease progression). Overall, 144 (97%) of 149 patients experienced treatment-related adverse events, which were mostly grade 1 or 2. The most common adverse events were visual effects, nausea, diarrhoea, constipation, vomiting, and peripheral oedema. The most common treatment-related grade 3 or 4 adverse events were neutropenia (n=9), raised alanine aminotransferase (n=6), hypophosphataemia (n=6), and lymphopenia (n=6). Crizotinib is well tolerated with rapid, durable responses in patients with ALK-positive NSCLC. There seems to be potential for ongoing benefit after initial disease progression in this population, but a more formal definition of ongoing benefit in this context is needed. Pfizer.

Background Fibroids are non-cancerous uterine growths that can cause symptoms impacting quality of life. The breadth of treatment options allows for patient-centered preference. While conversation aids are known to facilitate shared decision making, the implementation of these aids for uterine fibroids treatments is limited. We aimed to develop two end-user-acceptable uterine fibroids conversation aids for an implementation project. Our second aim was to outline the adaptations that were made to the conversation aids as implementation occurred. Methods We used a multi-phase user-centered participatory approach to develop a text-based and picture-enhanced conversation aid for uterine fibroids. We conducted a focus group with project stakeholders and user-testing interviews with eligible individuals with symptomatic uterine fibroids. We analyzed the results of the user-testing interviews using Morville’s Honeycomb framework. Spanish translations of the conversation aids occurred in parallel with the English iterations. We documented the continuous adaptations of the conversation aids that occurred during the project using an expanded framework for reporting adaptations and modifications to evidence-based interventions (FRAME). Results The first iteration of the conversation aids was developed in December 2018. Focus group participants ( n  = 6) appreciated the brevity of the tools and suggested changes to the bar graphs and illustrations used in the picture-enhanced version. User-testing with interview participants ( n  = 9) found that both conversation aids were satisfactory, with minor changes suggested. However, during implementation, significant changes were suggested by patients, other stakeholders, and participating clinicians when they reviewed the content. The most significant changes required the addition or deletion of information about treatment options as newer research was published or as novel interventions were introduced into clinical practice. Conclusions This multi-year project revealed the necessity of continuously adapting the uterine fibroids conversation aids so they remain acceptable in an implementation and sustainability context. Therefore, it is important to seek regular user feedback and plan for the need to undertake updates and revisions to conversation aids if they are going to be acceptable for clinical use.

Teachers' self-reported assessment practices and the influence of teaching experience, grade level, and subject area on those practices were explored in this study. Questionnaires were administered to 893 teachers in 34 schools. Teachers reported using performance and observation-based assessment methods most frequently and had the most confidence in the validity of these assessment techniques. Correlational analyses revealed that the more teachers reported using alternative methods of assessment, the more likely they were to report feeling prepared to develop those types of assessments and to report being confident in their validity. The same pattern of results was found for more traditional types of assessment. The most experienced teachers (20 years or more) indicated that they used alternative methods of assessment more often than the least experienced teachers (6 years or less) did. Elementary school teachers reported using alternative assessment strategies significantly more often than did high school teachers. Finally, mathematics teachers reported using traditional methods of assessment much less frequently than did teachers in all other subject areas.