Citations

Objectives This pilot study aimed to determine the effect of nurse/physician interdisciplinary team training on patient falls. Specifically, we evaluated team training in a simulation center as a method for targeting and minimizing breakdowns in perceptions of respect, collaboration, communication, and role misunderstanding behaviors between care disciplines. Methods Registered nurses (RNs) were randomly assigned to participate. Residents were divided into groups and assigned based on their availability and clinical responsibility. All participants completed a demographic form, the Professional Practice Environment Assessment Scale (PPEAS), and the Mayo High Performance Teamwork Scale (MHPTS) after consenting and before participation in simulation training. The PPEAS and the MHPTS were readministered at 2 and 6 months after the simulation experience. Differences in MHPTS and PPEAS scores between the baseline and 2- and 6-month assessments were analyzed; fall rates over time were evaluated using Cochran-Armitage trend tests. Results After the team training exercises, teamwork as measured by the MHPTS improved significantly at both 2 and 6 months (P = 0.01; P < 0.001) compared with baseline measurement. Practice environment subscores, with the exception of positive organizational characteristics, also increased when measured 6 months after training. The primary outcome, reduction in anticipated patient falls, improved significantly (P = 0.02) over the course of the study. Conclusions Results of this pilot study show that team training exercises result in improvement in both patient safety (anticipated patient falls) and team member perception of their work environment. If validated by other studies, improvement in this patient safety metric would represent an important benefit of simulation and team training.

Noonan syndrome (NS; MIM 163950) is an autosomal dominant disorder and a member of a family of developmental disorders termed “RASopathies,” which are caused mainly by gain-of-function mutations in genes encoding RAS/MAPK signaling pathway proteins. Whole exome sequencing (WES) and trio-based genomic triangulation of a 15-year-old female with a clinical diagnosis of NS and concomitant cardiac hypertrophy and her unaffected parents identified a de novo variant in MRAS -encoded RAS-related protein 3 as the cause of her disease. Mutation analysis using in silico mutation prediction tools and molecular dynamics simulations predicted the identified variant, p.Gly23Val-MRAS, to be damaging to normal protein function and adversely affect effector interaction regions and the GTP-binding site. Subsequent ectopic expression experiments revealed a 40-fold increase in MRAS activation for p.Gly23Val-MRAS compared with WT-MRAS. Additional biochemical assays demonstrated enhanced activation of both RAS/MAPK pathway signaling and downstream gene expression in cells expressing p.Gly23Val-MRAS. Mutational analysis of MRAS in a cohort of 109 unrelated patients with phenotype-positive/genotype-negative NS and cardiac hypertrophy yielded another patient with a sporadic de novo MRAS variant (p.Thr68Ile, c.203C>T). Herein, we describe the discovery of mutations in MRAS in patients with NS and cardiac hypertrophy, establishing MRAS as the newest NS with cardiac hypertrophy-susceptibility gene.

Objectives/HypothesisChildren with bilateral true vocal fold immobility (BTVFI) may present with significant airway distress necessitating tracheostomy. The objective of this study was to review our preliminary experience with the anterior–posterior cricoid split (APCS), an endoscopic intervention used as an alternative to tracheostomy in children with BTVFI.Study DesignMulticenter review.MethodsA review of patients undergoing endoscopic APCS for BTVFI at four institutions was performed. Patients were evaluated for the ability to ventilate without the requirement for tracheostomy or reintubation. Additional data extracted included the duration of intubation following APCS, the requirement for additional procedures, and demographics. Surgical success was defined as the ability to avoid tracheostomy and to cap or decannulate without respiratory symptoms if a tracheostomy was present prior to APCS.ResultsNineteen APCS procedures were performed between October 2010 and June 2016. There were 12 male patients, the mean age at APCS was 4.7 months. BTVFI was primarily idiopathic (58%) and associated with other comorbidities (74%). All patients were candidates for tracheostomy prior to APCS. Fourteen patients (74%) were considered surgical successes. Of the unsuccessful patients, three (66%) required tracheostomy following APCS, and one was treated with a posterior cartilage graft. There was one nonsurgical mortality greater than 2 months after APCS and thought to be unrelated to the airway.ConclusionsEndoscopic APCS appears to be a safe and effective intervention for pediatric BTVFI. Under the correct circumstances, this can be performed as a single procedure, obviating tracheostomy. Further study is warranted.Level of Evidence4. Laryngoscope, 128:257–263, 2018

Abstract Purpose: Cyclin-dependent kinase (CDK) 4/6 drives cell proliferation in estrogen receptor–positive (ER+) breast cancer. This single-arm phase II neoadjuvant trial (NeoPalAna) assessed the antiproliferative activity of the CDK4/6 inhibitor palbociclib in primary breast cancer as a prelude to adjuvant studies. Experimental Design: Eligible patients with clinical stage II/III ER+/HER2− breast cancer received anastrozole 1 mg daily for 4 weeks (cycle 0; with goserelin if premenopausal), followed by adding palbociclib (125 mg daily on days 1–21) on cycle 1 day 1 (C1D1) for four 28-day cycles unless C1D15 Ki67 &gt; 10%, in which case patients went off study due to inadequate response. Anastrozole was continued until surgery, which occurred 3 to 5 weeks after palbociclib exposure. Later patients received additional 10 to 12 days of palbociclib (Cycle 5) immediately before surgery. Serial biopsies at baseline, C1D1, C1D15, and surgery were analyzed for Ki67, gene expression, and mutation profiles. The primary endpoint was complete cell cycle arrest (CCCA: central Ki67 ≤ 2.7%). Results: Fifty patients enrolled. The CCCA rate was significantly higher after adding palbociclib to anastrozole (C1D15 87% vs. C1D1 26%, P &lt; 0.001). Palbociclib enhanced cell-cycle control over anastrozole monotherapy regardless of luminal subtype (A vs. B) and PIK3CA status with activity observed across a broad range of clinicopathologic and mutation profiles. Ki67 recovery at surgery following palbociclib washout was suppressed by cycle 5 palbociclib. Resistance was associated with nonluminal subtypes and persistent E2F-target gene expression. Conclusions: Palbociclib is an active antiproliferative agent for early-stage breast cancer resistant to anastrozole; however, prolonged administration may be necessary to maintain its effect. Clin Cancer Res; 23(15); 4055–65. ©2017 AACR.

Abstract Effective assessment and management of pain in patients with cancer is strengthened by the patient's report of how much pain interferes with daily functioning. This requires a clear delineation of different levels of pain interference. We derived optimal cutpoints for differentiating between mild, moderate, and severe pain interference assessed by the Brief Pain Inventory (BPI) and describe the prevalence and characteristics of pain-induced functional impairment in patients with cancer. Data were pooled across 3 Phase III pivotal trials. Patient-completed questionnaires included the EuroQol 5 dimensions questionnaire (EQ5D), Functional Assessment of Cancer Therapy–General Measure (FACT-G), and BPI. Optimal cutpoints for categorizing pain interference into 3 levels were derived using analysis of variance, with different cutpoint sets for BPI total interference (BPI-PITS, the average score of all 7 items), activity-related interference (BPI-WAW, the average score of work, general activity, and walking), and mood-related interference (BPI-REM, the average score of relations with others, enjoyment of life, and mood) as independent variables and EQ5D–visual analog scale and total FACT-G score as dependent variables. To validate the cutpoints, we assessed whether interference categories were in concordance with Eastern Cooperative Oncology Group performance status (ECOG-PS) levels. The optimal cutpoints were (2,5) for BPI-PITS, (2,6) for BPI-WAW, and (2,5) for BPI-REM. The mild (<2), moderate (2-5 or 2-6), and severe (>5 or >6) pain interference groups were significantly concordant with ECOG-PS levels (P < 0.0001). We empirically derived patient-reported pain interference categories in relation to clinician-rated performance status. These cutpoints may facilitate the conduct and interpretation of clinical evaluation, symptom epidemiology, and clinical trials.