Explore the vast range of titles available.

In patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation, the addition of daratumumab to bortezomib, melphalan, and prednisone increased progression-free survival and the response rate at the cost of an increase in infections.

In patients with melanomas containing activating BRAF mutations, the combination of a BRAF inhibitor and a MEK inhibitor improved overall survival, as compared with a BRAF inhibitor alone, and was associated with many fewer second skin tumors. The treatment of metastatic melanoma is rapidly evolving. The potent and specific BRAF inhibitors vemurafenib and dabrafenib, as compared with chemotherapy, have significantly improved response rates, along with progression-free and overall survival, in patients with metastatic melanoma with BRAF V600E or V600K mutations. 1 , 2 However, acquired resistance to BRAF inhibitors frequently develops through reactivation of the mitogen-activated protein kinase (MAPK) pathway, resulting in a median progression-free survival of 6 to 8 months. 2 – 5 In addition, the use of BRAF inhibitors may result in the development of secondary skin tumors, originating from a paradoxical activation of the MAPK pathway in cells . . .

Purpose To characterize the pharmacokinetics of oral trametinib, a first in class MEK inhibitor, identify covariates, and describe the relationship between exposure and clinical effects in patients with BRAF V600 metastatic melanoma. Experimental design Trametinib concentrations obtained in three clinical studies were included in the population pharmacokinetic analysis. Trametinib 2 mg once daily was administered in the Phase 2 and 3 studies. The impact of exposure [trough ( C min ) or average concentration] on response rates and progression-free survival (PFS) was examined. Results Plasma concentrations ( n  = 3120) obtained in 493 patients were described using a two-compartment model. Trametinib oral clearance was lower in women relative to men (1.26-fold) and increased with body weight. There was no significant effect of age, mild or moderate renal impairment, or mild hepatic impairment on oral clearance. Between-subject variability was low (24 %). The number of responders was consistent across median exposure range, although tended to be lower at trough concentration <10 ng/mL. Disease stage was found to be a significant predictor of response with a lower response rate in patients with disease stage of M1c. Lactate dehydrogenase was significant in the analysis of PFS. Patients with observed C min above the median had longer PFS than those below median based on Phase 2 study (median 10.6 ng/mL), while the effect of exposure was not statistically significant in the Phase 3 study (median 13.6 ng/mL). Conclusions No dosage adjustments are required with any of the covariates tested. Clinical efficacy was associated with trametinib trough concentrations greater than 10 ng/mL.

In the ALCYONE trial, daratumumab plus bortezomib, melphalan, and prednisone (D-VMP) reduced the risk of disease progression or death by 50% versus bortezomib, melphalan, and prednisone (VMP) in patients with transplant-ineligible newly diagnosed multiple myeloma. Here, we report a subanalysis of East Asian patients from ALCYONE. After a median follow-up of 17.1 and 15.9 months for Japanese (n = 50) and Korean (n = 41) patients, respectively, median progression-free survival for D-VMP versus VMP was not reached (NR) versus 20.7 months in Japanese patients and NR versus 14.0 months in Korean patients. The overall response rate for D-VMP versus VMP was 96% versus 92% in Japanese patients and 91% versus 61% in Korean patients. Using next-generation sequencing, minimal residual disease negativity at 10−5 sensitivity for D-VMP versus VMP was 33% versus 8% among Japanese patients and 17% versus 0% among Korean patients. Rates of any grade and grade 3/4 pneumonia were consistent with the rates observed for the global safety population. Similar efficacy and safety findings were observed in the combined Japanese and Korean subgroup and ≥ 75 years of age subgroup. In conclusion, D-VMP was safe and efficacious in East Asian patients, consistent with the global ALCYONE population.

Considerable progress has been made but, according to statistics, Canada still has a long way to go. One of the most effective and immediate ways to assist women and their families alike is to make the rearing and well-being of children easier. The first step might be to introduce universal childcare, another is to pay women the same wages and salaries for the same job as any other person. A third way is to raise minimum wages and remove income taxes from low- income families, and a fourth is to provide free education and enhanced training for women.

The endless cycle of more concrete for cars is being repeated while congestion and pollution are escalating. Recent stories in the Vancouver press about air quality in the Lower Mainland tell the tale. Asthma-related diseases, especially among children and seniors, are on the rise.

Whatever the merits of last week's international forum in Vancouver on urban issues, it provided an opportunity for a reality check for our homegrown patriots who prefer to see no evil, hear no evil and speak no evil. Vancouver's natural setting ranks undoubtedly near the top among the world's harbours.

Acute care physical therapy is a rapidly evolving practice area, but little is known about the skills, knowledge, and behaviors necessary for a clinician to be most effective in this area. The objective of this study was to perform the first nationwide survey of acute care physical therapists to validate the knowledge, skill, and behavior sets that reflect practice parameters specific for acute care physical therapy. A survey format was used. The Acute Care Physical Therapy Practice Analysis Survey was created on the basis of current literature and consensus of a 9-member Subject Matter Expert (SME) Group. The survey sections addressed knowledge areas, professional behaviors, and patient/client management approaches reflecting practice parameters specific for acute care physical therapy. Additionally, respondent demographic information was collected. Pilot testing necessitated minor changes in the survey. After revision, the survey questionnaire was sent to a sample of experienced acute care physical therapists throughout the United States. A convenience sample of 522 physical therapists who identified themselves as having extensive experience in acute care practice was used. Of these, 254 completed the survey, for a response rate of 48.7%. Through the use of predetermined decision rules, 34 items were eliminated on the basis of a descriptive analysis of survey results as well as a failure of the items to meet the threshold of specificity for acute care practice, as determined through SME Group consensus. The potential for self-selection bias, a sample weighted heavily with American Physical Therapy Association members and Acute Care Section members, and a small proportion of clinicians (<3%) with less than 1 year of acute care experience may limit generalizability of these results. The results of this practice analysis describe distinct knowledge, skills, and behaviors specific for acute care physical therapy. The outcomes of the survey might assist in the development of professional (entry-level) acute care competencies, a petition for the recognition of specialization in acute care physical therapy, or both. In addition, the findings of this practice analysis could serve as the foundation for the development of residencies or fellowships in acute care practice.

Background Loss of contact between radial head fracture fragments is strongly associated with other elbow or forearm injuries. If this finding has adequate interobserver reliability, it could help examiners identify and treat associated ligament injuries and fractures (eg, forearm interosseous ligament injury or elbow dislocation). Questions/purposes (1) What is the interobserver agreement on radiographic loss of contact between radial head fracture fragments? (2) Are there factors associated with the observer such as location of practice or subspecialization that increase interobserver reliability? Methods Fully trained practicing orthopaedic and trauma surgeons from around the world evaluated 27 anteroposterior and lateral radiographs of radial head fractures on a web-based platform for the following characteristics: (1) loss of contact between at least one radial head fracture fragment and the remaining radial head and neck; (2) a gap between fragments of 2 mm or greater; (3) anticipated fracture instability (mobility) on operative exposure; (4) anticipated associated ligament injuries; and (5) recommendation for treatment. Agreement among observers was measured using the multirater kappa measure. Kappas for various observer characteristics were compared using 95% confidence intervals. Results The overall interobserver agreement was moderate (range, 0.49–0.55) for each question except associated ligament injury, which was fair (0.33). Shoulder and elbow surgeons had substantial agreement (range, 0.51–0.61) in many areas, but kappas were generally in the moderate range (0.41–0.59) based on number of years in practice, radial head fractures treated per year, and trainee supervision. Conclusions Radiographic signs of radial head fracture instability such as loss of contact have moderate reliability. This characteristic seems clinically useful, because loss of contact between at least one radial head fracture fragment and the remaining radial head and neck is strongly associated with associated ligament injury or other fractures. Level of Evidence Level III, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence.