Updated analysis of CALGB (Alliance) 100104 assessing lenalidomide versus placebo maintenance after single autologous stem-cell transplantation for multiple myeloma: a randomised, double-blind, phase 3 trial.

BACKGROUND: In the CALGB (Alliance) 100104 study, lenalidomide versus placebo after autologous stem-cell transplantation (ASCT) was investigated for patients with newly diagnosed myeloma. That study showed improved time to progression and overall survival and an increase in second primary malignancies for lenalidomide at a median follow-up of 34 months. Here we report an updated intention-to-treat analysis of CALGB (Alliance) 100104 at a median follow-up of 91 months. METHODS: Patients were eligible for this randomised, double-blind, placebo-controlled, phase 3 trial if they had symptomatic disease requiring treatment; had received, at most, two induction regimens; and had achieved stable disease or better in the first 100 days after ASCT. We randomly assigned patients to either lenalidomide or placebo groups using permuted block randomisation, with a fixed block size of six. Randomisation was stratified by three factors: normal or elevated ß2 microglobulin concentration at registration (≤2·5 mg/L vs >2·5 mg/L), previous use or non-use of thalidomide during induction therapy, and previous use or non-use of lenalidomide during induction therapy. The starting dose was two capsules (10 mg) per day, escalated to three capsules (15 mg) per day after 3 months. The primary endpoint was time to progression (time of progressive disease or death from any cause), with intention-to-treat analysis. This study is registered with ClinicalTrials.gov, identifier NCT00114101. New patients are no longer being recruited, but some patients remain on treatment and in follow-up. FINDINGS: Between April 14, 2005, and July 2, 2009, 460 patients were randomly assigned to receive either lenalidomide (n=231) or placebo (n=229). After three interim analyses, the study was unblinded at a median follow-up of 18 months, at which point 86 (67%) of 128 patients without progressive disease in the placebo group chose to cross over to the lenalidomide group. The median follow-up for the updated survival analysis, as of Oct 19, 2016, was 91 months (IQR 83·6-103·1). The median time to progression was 57·3 months (95% CI 44·2-73·3) for the lenalidomide group and 28·9 months (23·0-36·3) for the placebo group (hazard ratio 0·57, 95% CI 0·46-0·71; p<0·0001). The most common grade 3-4 adverse events were neutropenia (116 [50%] patients in the lenalidomide group and 41 [18%] patients in the placebo group) and thrombocytopenia (34 [15%] patients in the lenalidomide group and 12 [5%] patients in the placebo group). 18 (8%) haematological and 14 (6%) solid tumour second primary malignancies were diagnosed after randomisation and before disease progression in the lenalidomide group, compared with three (1%) haematological and nine (4%) solid tumour second primary malignancies in the placebo group. Three haematological and five solid tumour second primary malignancies in the placebo group were in the crossover subgroup. INTERPRETATION: Despite an increase in haematological adverse events and second primary malignancies, lenalidomide maintenance therapy after ASCT significantly improved time to progression and could be considered a standard of care. FUNDING: The National Cancer Institute.

Levels and patterns of physical activity and sedentary time among superdiverse adolescents in East London: a cross-sectional study.

OBJECTIVES: Little is known about the physical activity (PA) and sedentary time (ST) habits of adolescents from superdiverse communities in the UK. The objectives of this study are to examine and report the patterns of PA/ST among adolescents in East London living in superdiverse communities, to identify opportunities/barriers to PA and inform policy/practice. DESIGN: A total of 1260 young people (aged 11-13 years) from seven secondary schools in East London completed a questionnaire on PA/ST over the past seven days as part of the Newham's Every Child a Sports Person (NECaSP) intervention. Socio-demographic and anthropometric data were obtained. Significance tests were conducted to determine differences between socio-demographic and anthropometric predictors and PA/ST. Multinomial logit regression was used to explore the effects of ethnicity, sex, and body mass index (BMI) on PA levels. RESULTS: Males were significantly more likely to engage in PA at least five times during school in the past week (U = 5.07, z = -11.76, p < .05). Obese participants were less likely to report engaging in PA five times in the past week (U = 4.11, z =-1.17, p < .05). Black Caribbean girls (U = 5.08, z = -1.92, p < .05) were significantly more likely to report engaging in no activity. Multinomial logit regression analyses revealed that girls with higher BMI were less likely to engage in PA at least four times after school in the last week than boys (b = .11, Wald X2(1) = 9.81, p < .01). Walking (36.4%), jogging/running (29.9%), and football (28%) were the most frequently reported activities. CONCLUSION: Engaging girls in PA during and after school is important and making sports clubs and activities available and attractive to this target group may help increase engagement in PA and reduce ST. Findings support the need for more sex-specific and culturally responsive pedagogy in schools with curricula that respects diversity and individuality and has meaning and value amongst superdiverse young people. Finally, we need to extend current work presented and provide substantial evidence of the ways young people from minority ethnic groups process and act on the public health policy and the ways they understand and enact PA.

Newham's Every Child a Sports Person (NECaSP): A Summative Process Evaluation of a School- and Community- Based Intervention in East London, United Kingdom.

BACKGROUND: The Newman's Every Child a Sports Person (NECaSP) intervention aspires to increase sport and physical activity (PA) participation among young people in the United Kingdom. The aims of this article are to report on a summative process evaluation of the NECaSP and make recommendations for future interventions. METHODS: Seventeen schools provided data from students aged 11 to 13 years (n = 1226), parents (n = 192), and teachers (n = 14) via direct observation and questionnaires. Means, SDs, and percentages were calculated for sociodemographic data. Qualitative data were analyzed via directed content analysis and main themes identified. RESULTS: Findings indicate further administrative, educational, and financial support will help facilitate the success of the program in improving PA outcomes for young people and of other similar intervention programs globally. Data highlighted the need to engage parents to increase the likelihood of intervention success. CONCLUSIONS: One main strength of this study is the mixed-methods nature of the process evaluation. It is recommended that future school-based interventions that bridge sports clubs and formal curriculum provision should consider a broader approach to the delivery of programs throughout the academic year, school week, and school day. Finally, changes in the school curriculum can be successful once all parties are involved (community, school, families).

Giving back during national nurses week.

In lieu of gifts, RNs donate their services, time, and money.

A quality improvement framework for equity in cardiovascular care: results of a national collaborative.

Disparities in the quality of cardiovascular care provided to minorities have been well documented, but less is known about the use of quality improvement methods to eliminate these disparities. Measurement is also often impeded by a lack of reliable patient demographic data. The objective of this study was to assess the ability of hospitals with large minority populations to measure and improve the care rendered to Black and Hispanic patients. The Expecting Success: Excellence in Cardiac Care project utilized the standardized collection of self-reported patient race, ethnicity, and language data to generate stratified performance measures for cardiac care coupled with evidence-based practice tools in a national competitively selected sample of 10 hospitals with high cardiac volumes and largely minority patient populations. Main outcomes included changes in nationally recognized measures of acute myocardial infarction and heart failure quality of care and 2 composite measures, stratified by patient demographic characteristics. Quality improved significantly at 7 of the 10 hospitals as gauged by composite measures (p < .05), and improvements exceeded those observed nationally for all hospitals. Three of 10 hospitals found racial or ethnic disparities which were eliminated in the course of the project. Clinicians and institutions were able to join the standardized collection of self-reported patient demographic data to evidence-based measures and quality improvement tools to improve the care of minorities and eliminate disparities in care. This framework may be replicable to ensure equity in other clinical areas.

The past, present, and future of urgent matters: lessons learned from a decade of emergency department flow improvement.

Over the past decade, emergency departments (ED) have encountered major challenges due to increased crowding and a greater public focus on quality measurement and quality improvement. Responding to these challenges, many EDs have worked to improve their processes and develop new and innovative models of care delivery. Urgent Matters has contributed to ED quality and patient flow improvement by working with hospitals throughout the United States. Recognizing that EDs across the country are struggling with many of the same issues, Urgent Matters-a program funded by the Robert Wood Johnson Foundation (RWJF)-has sought to identify, develop, and disseminate innovative approaches, interventions, and models to improve ED flow and quality. Using a variety of techniques, such as learning networks (collaboratives), national conferences, e-newsletters, webinars, best practices toolkits, and social media, Urgent Matters has served as a thought leader and innovator in ED quality improvement initiatives. The Urgent Matters Seven Success Factors were drawn from the early work done by program participants and propose practical guidelines for implementing and sustaining ED improvement activities. This article chronicles the history, activities, lessons learned, and future of the Urgent Matters program.

Predicting BRCA1 and BRCA2 gene mutation carriers: comparison of PENN II model to previous study.

A number of models have been developed to predict the probability that a person carries a detectable germline mutation in the BRCA1 or BRCA2 genes. Their relative performance in a clinical setting is variable. To compare the performance characteristics of a web-based BRCA1/BRCA2 gene mutation prediction model: the PENNII model ( www.afcri.upenn.edu/itacc/penn2 ), with studies done previously at our institution using four other models including LAMBDA, BRCAPRO, modified PENNI (Couch) tables, and Myriad II tables collated by Myriad Genetics Laboratories. Proband and family cancer history data were analyzed from 285 probands from unique families (27 Ashkenazi Jewish; 277 female) seen for genetic risk assessment in a multispecialty tertiary care group practice. All probands had clinical testing for BR.CA1 and BRCA2 mutations conducted in the same single commercial laboratory. The performance for PENNII results were assessed by the area under the receiver operating characteristic curve (AUC) of sensitivity versus 1-specificity, as a measure of ranking. The AUCs of the PENNII model were higher for predicting BRCA1 than for BRCA2 (81 versus 72%). The overall AUC was 78.7%. PENN II model for BRCA1/2 prediction performed well in this population with higher AUC compared with our experience using four other models. The ease of use of the PENNII model is compatible with busy clinical practices.

Assumed equity: early observations from the first hospital disparities collaborative.

Disparities in healthcare represent a failure in the equity domain of quality. Although disparities have been well documented, little has been written about how hospitals might use improved data collection and quality improvement techniques to eliminate disparities. This article describes early findings from the planning phase of the first hospital-based disparities collaborative. The authors also discuss the changes in policy and practice that may speed hospitals in placing disparities and equity on their quality agendas.

Predicting BRCA1 and BRCA2 gene mutation carriers: comparison of LAMBDA, BRCAPRO, Myriad II, and modified Couch models.

CONTEXT: Models have been developed to predict the probability that a person carries a detectable germline mutation in the BRCA1 or BRCA2 genes. Their relative performance in a clinical setting is unclear. OBJECTIVE: To compare the performance characteristics of four BRCA1/BRCA2 gene mutation prediction models: LAMBDA, based on a checklist and scores developed from data on Ashkenazi Jewish (AJ) women; BRCAPRO, a Bayesian computer program; modified Couch tables based on regression analyses; and Myriad II tables collated by Myriad Genetics Laboratories. DESIGN AND SETTING: Family cancer history data were analyzed from 200 probands from the Mayo Clinic Familial Cancer Program, in a multispecialty tertiary care group practice. All probands had clinical testing for BRCA1 and BRCA2 mutations conducted in a single laboratory. MAIN OUTCOMES MEASURES: For each model, performance was assessed by the area under the receiver operator characteristic curve (ROC) and by tests of accuracy and dispersion. Cases "missed" by one or more models (model predicted less than 10% probability of mutation when a mutation was actually found) were compared across models. RESULTS: All models gave similar areas under the ROC curve of 0.71 to 0.76. All models except LAMBDA substantially under-predicted the numbers of carriers. All models were too dispersed. CONCLUSIONS: In terms of ranking, all prediction models performed reasonably well with similar performance characteristics. Model predictions were widely discrepant for some families. Review of cancer family histories by an experienced clinician continues to be vital to ensure that critical elements are not missed and that the most appropriate risk prediction figures are provided.

Enhancing work flow to reduce crowding.

INTRODUCTION: Approximately one third of hospitals in the United States report increases in ambulance diversion in a given year, whereas up to half report crowded conditions in the emergency department (ED). In a recent national survey, 40% of hospital leaders viewed ED crowding as a symptom of workforce shortages. Many health systems are implementing a variety of strategies to improve flow and reduce crowding. DOMAINS OF IMPROVEMENT: Virtually all work-flow initiatives use operations management techniques that include some or all of four domains: performance measurement, demand forecasting, flow redesign, and capacity management. These are often implemented using rapid improvement techniques. Most initiatives tend to focus on functional increases in inpatient capacity. IMPLICATIONS FOR PRACTICE AND POLICY: Successful strategies to improve patient flow are distinguished by an organizationwide commitment to measurement, transparency in data reporting, and sustained management attention. Focusing on transitions between ED and inpatient units and maximizing overall hospital capacity appears necessary for improvement. Hence, reductions in ED crowding require strategies that go far beyond the ED. CONCLUSION: Health systems can take tangible, immediate steps to improve flow and reduce crowding. Efforts would be enhanced by more controlled trials of existing strategies in the context of uniform performance measures.

Desmoid tumors -- a characterization of patients seen at Mayo Clinic 1976-1999.

Desmoid tumors occur with high frequency in individuals with Familial Adenomatous Polyposis (FAP). Because of this, individuals developing desmoid tumors may be referred for genetic risk assessment. Determining whether a person has a FAP-related desmoid tumor or a sporadic desmoid can be challenging. We sought to characterize the patients who were seen at our institution to determine if there were clinical differences in presentation between FAP-associated and sporadic desmoid tumors. We searched the Mayo Clinic-modified H-ICDA (Hospital adaptation of the International Classification of Diseases) diagnostic codes for all diagnoses of desmoid tumors in patients seen between 1976 and 1999. Charts were reviewed to determine accuracy of diagnosis, age when seen, gender, site of tumor, and presence of polyposis. A total of 454 patients (174 males and 280 females) met the search criterion. Of the 447 patients on whom all data was obtained, 70 had FAP and 377 had no evidence of FAP. The female/male ratio for FAP cases was 1.12 compared to female/male ratio of 1.71 for non-FAP cases. (P=0.17). Location of development of desmoid tumors was correlated with but not specific for distinguishing FAP from non-FAP desmoids. Abdominal desmoids comprised the majority of FAP desmoids and extra-abdominal desmoids comprised the majority of non-FAP desmoids (P<0.001) but age was not a discriminating factor. Using Bayesian analysis, we demonstrate how these findings can assist genetic professionals in their evaluation of patients with desmoid tumors by providing prior probabilities of FAP based upon clinical presentation.