A real-world study of second or later-line osimertinib in patients with EGFR T790M-positive NSCLC: the final ASTRIS data.

Aim: Report the final analysis from ASTRIS, the largest real-world study of second-/later-line osimertinib in advanced/metastatic EGFR T790M non-small-cell lung cancer (NSCLC). Methods: Patients with advanced/metastatic EGFR T790M NSCLC and prior EGFR-TKI treatment, received once-daily osimertinib 80 mg. Primary end point: overall survival (OS); secondary end points: progression-free survival (PFS), time-to-treatment discontinuation (TTD) and response rate. Safety was also recorded. Results: In 3014 patients, median OS: 22.8 months (21.6-23.8), median PFS: 11.1 months (11.0-12.0), median TTD: 13.5 months (12.6-13.9), and response rate: 57.3% (55.5-59.2). All end points reported with 95% CIs. Numerically longer median OS was observed in patients with baseline WHO performance status <2 versus 2 (24.0 vs 11.1 months) and those without versus with brain/leptomeningeal metastases (25.4 vs 18.0 months). No new safety signals were identified. Conclusion: Second-/later-line osimertinib demonstrated real-world clinical benefit and safety in advanced/metastatic EGFR T790M NSCLC. Clinical Trial Registration: NCT02474355 (ClinicalTrials.gov).

Osimertinib is a drug that blocks the activity of a protein called EGFR on cancer cells, reducing their growth and spread. ASTRIS is the largest real-world study that evaluated the outcomes with osimertinib treatment for patients with advanced non-small-cell lung cancer (NSCLC), and the EGFR T790M mutation, who had received previous treatment for their cancer. There were 3014 patients included in this study. The main aim of this study was to measure the time at which half of the patients were still alive after starting osimertinib treatment, this was 22.8 months. The study also measured the time at which half of the patients had experienced worsening (progression) of their cancer (11.1 months) and the time when half of the patients had stopped receiving osimertinib treatment (13.5 months). None of the patients experienced any unexpected side effects of the treatment. These data are consistent with those observed in comparable clinical trials with osimertinib, supporting the use of osimertinib treatment for patients with advanced NSCLC and the EGFR T790M mutation after their initial cancer treatment has stopped working.

A Phase 1 study of gefitinib combined with durvalumab in EGFR TKI-naive patients with EGFR mutation-positive locally advanced/metastatic non-small-cell lung cancer.

BACKGROUND: EGFR tyrosine kinase inhibitors (TKIs) induce cytolysis and release of tumour proteins, which can stimulate antigen-specific T cells. The safety and efficacy of durvalumab and gefitinib in combination for TKI-naive patients with advanced EGFRm NSCLC was evaluated. METHODS: This Phase 1 open-label, multicentre trial (NCT02088112) was conducted in 56 patients with NSCLC. Dose expansion permitted TKI-naive patients, primarily with activating L858R or Ex19del EGFRm. Arms 1 + 1a received concurrent therapy; Arm 2 received 4 weeks of gefitinib induction followed by concurrent therapy. RESULTS: From dose escalation, the recommended dose of durvalumab was 10 mg/kg Q2W with 250 mg QD gefitinib. Pharmacokinetics were as expected, consistent with inhibition of soluble PD-L1 and no treatment-emergent immunogenicity. In dose expansion, 35% of patients had elevated liver enzymes leading to drug discontinuation. In Arms 1 + 1a, objective response rate was 63.3% (95% CI: 43.9-80.1), median progression-free survival (PFS) was 10.1 months (95% CI: 5.5-15.2) and median response duration was 9.2 months (95% CI: 3.7-14.0). CONCLUSIONS: Durvalumab and gefitinib in combination had higher toxicity than either agent alone. No significant increase in PFS was detected compared with historical controls. Therefore, concurrent PD-L1 inhibitors with gefitinib should be generally avoided in TKI-naive patients with EGFRm NSCLC.

An Exploratory Study of Bullying Exposure Among School Nurses: Prevalence and Impact.

The frequency and consequences of bullying directed at school nurses (SNs) are poorly understood. The purpose of this study was to describe the prevalence and impact of bullying directed at school nurses, determine predictors of bullying directed at school nurses, and evaluate the individual and organizational impact of exposure to bullying directed at school nurses. School nurses (n = 334) completed an online survey comprised of the Negative Act Questionnaire-Revised, Perceived Stress Scale, National Institute for Occupational Safety and Health General Social Survey 2010 Quality of Worklife Module, Michigan Organizational Assessment Questionnaire, and open response items to determine their experiences with, and impact of, bullying. Descriptive and inferential statistics were calculated for quantitative data, while content analysis was used to analyze responses to open-ended survey items. One third of participants reported occasional or frequent bullying. Content analysis revealed three themes, including unexpected parent behavior, staff incivility, and formal reporting. Findings support the development of an educational intervention to assist school nurses in the prevention and management of bullying exposure.

Enactors of horizontal violence: The pathological bully, the self-justified bully and the unprofessional co-worker.

AIM: To suggest an alternative approach to improving recognition of horizontal violence using enactor types identified in a study exploring nurses' perceptions of horizontal violence. BACKGROUND: Horizontal violence is an umbrella term used to describe a range of aggressive behaviours between nurse colleagues. It is suggested that nurses do not recognize the phenomenon when they witness or experience it, contributing to its perpetuation. DESIGN: This was a qualitative, descriptive study undertaken to inform theory development and the design of future interventions to address horizontal violence. METHOD: Observation, document review and semi-structured interviews took place in two inpatient hospital units in the Northeastern United States between June - November 2012. Ongoing analysis identified three distinct types of enactors of horizontal violence. FINDINGS: Nurse participants rarely used terms from hospital policies or nursing literature to describe behaviours associated with horizontal violence but identified behaviours by describing the attributes of the enactor and the situation. Three enactor types were disaggregated from the data: the pathological bully, the self-justified bully and the unprofessional co-worker. CONCLUSION: Findings support previous research suggesting nurses do not recognize aggressive behaviours when they witness or experience them and do not have a name for those who enact these behaviours. This disaggregation of enactors of horizontal violence into recognizable types introduces an alternative approach to addressing the phenomenon. Development of instruments to identify these enactors, as well as testing of these instruments, is required to establish the utility of this disaggregation in nursing practice and in designing future interventions.

Removal of nail polish and finger rings to prevent surgical infection.

BACKGROUND: Surgical wound infections may be caused by the transfer of bacteria from the hands of surgical teams to patients during operations. Surgical scrubbing prior to surgery reduces the number of bacteria on the skin, but wearing rings and nail polish on the fingers may reduce the efficacy of scrubbing, as bacteria may remain in microscopic imperfections of nail polish and on the skin beneath rings. OBJECTIVES: To assess the effect of the presence or absence of rings and nail polish on the hands of the surgical scrub team on postoperative wound infection rates. SEARCH METHODS: For this fifth update, we searched The Cochrane Wounds Group Specialised Register (searched 23 July 2014); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE and EBSCO CINAHL. SELECTION CRITERIA: Randomised controlled trials (RCTs) evaluating the effect of wearing or removing finger rings and nail polish on the efficacy of the surgical scrub and postoperative wound infection rate. DATA COLLECTION AND ANALYSIS: All abstracts were checked against a checklist to determine whether they fulfilled the inclusion criteria. Full reports of relevant studies were obtained. Excluded trial reports were checked by all review authors to ensure appropriate exclusion. MAIN RESULTS: We identified: no new trials; no RCTs that compared wearing of rings with the removal of rings; and no trials of nail polish versus no nail polish that measured surgical infection rates. We found one small RCT (102 scrub nurses) that evaluated the effect of nail polish on the number of bacterial colony forming units left on hands after pre-operative surgical scrubbing. Nurses had either unpolished nails, freshly-applied nail polish (less than two days old), or old nail polish (more than four days old). There were no significant differences in the number of bacteria on hands between the groups before and after surgical scrubbing. AUTHORS' CONCLUSIONS: No trials have investigated whether wearing nail polish or finger rings affects the rate of surgical wound infection. There is insufficient evidence to determine whether wearing nail polish affects the number of bacteria on the skin post-scrub.

The politics of securing borders and the identities of disease.

This article compares the policies adopted by Britain, France and Germany to cope with health threats thought to be posed by entrants and migrants and explains why these governments screened at their borders for tuberculosis but not for human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). In order to understand these outcomes, we must recognise that diseases acquire durable identities, conditioned by collective imaginaries and institutional contexts when they first come to attention, which bias subsequent decisions, notably about how to balance the value of mandatory testing against the rights of the individual.

Removal of nail polish and finger rings to prevent surgical infection.

BACKGROUND: Surgical wound infections may be caused by the transfer of bacteria from the hands of surgical teams to patients during operations. Surgical scrubbing prior to surgery reduces the number of bacteria on the skin, but wearing rings and nail polish on the fingers may reduce the efficacy of scrubbing, as bacteria may remain in microscopic imperfections of nail polish and on the skin beneath rings. OBJECTIVES: To assess the effect of the presence or absence of rings and nail polish on the hands of the surgical scrub team on postoperative wound infection rates. SEARCH METHODS: For this update, we searched The Cochrane Wounds Group Specialised Register (searched 27 January 2012); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 1); Ovid MEDLINE (2010 to January Week 2 2012); Ovid MEDLINE (In-Process & Other Non-Indexed Citations, January 26, 2012); Ovid EMBASE (2010 to 2012 Week 03); and EBSCO CINAHL (2010 to January 6 2012). SELECTION CRITERIA: Randomised controlled trials (RCTs) evaluating the effect of wearing or removing finger rings and nail polish on the efficacy of the surgical scrub and postoperative wound infection rate. DATA COLLECTION AND ANALYSIS: All abstracts were checked against a checklist to determine whether they fulfilled the inclusion criteria. Full reports of relevant studies were obtained. Excluded trial reports were checked by all authors to ensure appropriate exclusion. MAIN RESULTS: We identified: no new trials; no RCTs that compared wearing of rings with the removal of rings; and no trials of nail polish versus no nail polish that measured surgical infection rates. We found one small RCT (102 scrub nurses) that evaluated the effect of nail polish on the number of bacterial colony forming units left on hands after pre-operative surgical scrubbing. Nurses had either unpolished nails, freshly-applied nail polish (less than two days old), or old nail polish (more than four days old). There were no significant differences in the number of bacteria on hands between the groups before and after surgical scrubbing. AUTHORS' CONCLUSIONS: No trials have investigated whether wearing nail polish or finger rings affects the rate of surgical wound infection. There is insufficient evidence to determine whether wearing nail polish affects the number of bacteria on the skin post-scrub.

Public health in a transnational context: explaining Europe's role.

This commentary explores explanations for the EU's increasing involvement in public health. Through an examination of two case studies - policies on HIV/AIDS and preparations for pandemic influenza - it explores the process by which new ideas are disseminated in a policy sphere and the influence of law, economic interests, and international guidelines in making public health policy. It concludes by asking, with a comparative look at the United States, whether a European convergence on measures to control communicable disease is desirable.

Registered Nurses' Experiences With Incivility During the Early Phase of COVID-19 Pandemic: Results of a Multi-State Survey.

BACKGROUND: Incivility among workers in the health sector is recognized as an occupational hazard. The COVID-19 outbreak brought sudden and profound changes to many health care settings, many of which have been identified as antecedents to workplace incivility. The purpose of this retrospective study was to explore the experiences of registered nurses with workplace incivility, cyber-incivility, and incivility outside of work during the early phase of the COVID-19 pandemic. METHODS: This mixed-methods study used convenience sampling. Data were collected from June to September 2020 via an online survey, which consisted of both closed- and open-ended questions. Participants were recruited from national nursing organizations and unions. Data were analyzed using descriptive statistics and thematic analysis for open-ended responses. FINDINGS: A total of 526 nurses' responses were included in the analysis. More than one third experienced greater incivility at work during the COVID-19 outbreak than before the pandemic (37.4%), and almost half (45.7%) said they witnessed more incivility than before the pandemic. Cyber-incivility and incivility outside of work were also issues. Qualitative results indicated that respondents felt they were on edge during this period. Other themes included leadership failure, fractured co-worker relationships, heightened incivility from patients and families, and hostility and ostracism from the general public. CONCLUSION/APPLICATION TO PRACTICE: Occupational health nurses, nursing leaders, and staff nurses need to work to restore relations that were fractured by incivility during the pandemic. In the future, improved preparedness, including establishing clear channels of communication, may lessen incivility by decreasing role stress and organizational chaos.

An Exploratory Study of Bullying Directed Toward Clinical Nursing Faculty: Prevalence and Impact.

BACKGROUND: Clinical education is an integral component of nursing education and relies heavily on clinical nursing faculty (CNF). However, there are not enough nurses seeking CNF positions to meet the current demand of the nursing workforce. PURPOSE: The purpose of this study was to examine the prevalence and impact of workplace bullying directed toward CNF. METHODS: For this exploratory cross-sectional study, a web-based survey was distributed to CNF working in New England states. RESULTS: A total of 76 participant responses were analyzed. Eighteen percent of the participants met the criteria for being either occasionally or frequently bullied. Nursing staff in the clinical agencies and colleagues and administrators in the nursing program where CNF teach were identified as the most frequent perpetrators. CONCLUSIONS: Understanding the prevalence and impact of bullying of CNF helps inform the development of strategies to support and retain these essential members of the nursing education workforce.

Contemporary issues: Resilience training alone is an incomplete intervention.

Resilience training focuses on the individual to improve self-care, self-efficacy, and work/life balance with an aim to reduce burnout. However, the concept of resilience is complex and contextual, affected by the interplay between an individual and their environment. As such, any intervention to promote resilience in healthcare workers must recognize and address structural and organizational factors, as well as individual influences. Resilience-based approaches are often grounded in a strength-based model, emphasizing factors that promote success, while often overlooking factors that contribute to failure (Cross, 2015). Without examining and addressing factors in the work environment contributing to burnout, resilience training alone is an incomplete intervention.

Reframing and addressing horizontal violence as a workplace quality improvement concern.

AIM: To reframe horizontal violence as a quality improvement concern. BACKGROUND: Although the number of studies exploring horizontal violence has increased, evidence supporting the effectiveness of current interventions is weak and the problem persists. Often framed as an individual or interpersonal issue, horizontal violence has been recognized as a complex phenomenon that can only be understood through an examination of social, individual and organizational factors. As such, interventions to address horizontal violence must be applied systemically and address contributions from all sources. DESIGN: This is a discussion paper. DATA SOURCES: This discussion is based on results of a study of nurses' perceptions of horizontal violence and review of the literature. IMPLICATIONS FOR NURSING: Context is recognized as a contributing factor in human behavior, yet often overlooked in interventions to address horizontal violence. Moving the focus away from the individual and investigating systems contributions to horizontal violence using existing quality improvement frameworks is suggested. CONCLUSION: To date, efforts to address horizontal violence have not been proven effective. There is a call for a wider application and investigation of interventions. This reframing provides the system level application suggested and would address a broader range of factors contributing to the perpetuation of the phenomenon.

Stop the Eye Rolling: Supporting Nursing Students in Learning.

Too often, they face an unwelcoming introduction to the profession.

Making power visible: Doing theatre-based status work with nursing students.

As part of a senior leadership class in an undergraduate baccalaureate nursing program in the northeastern United States, we conducted an experiential, theater-based workshop designed to increase student awareness of the micro-dynamics of power and the enactment of status in their day-to-day lives. These exercises allowed student participants to embody status and power and understand it in ways that they did not after simply completing assigned readings. At the conclusion of the workshop the participants were asked to reflect on their status habits and the consequences of these habits in a single hand-written page. The participants' reflections showed two interesting trends. The first is that a relatively short workshop dramatically increased participants' awareness of power and status as ever present, including a substantial normative move from seeing using power as being a generally bad thing that can be justified in the interests of the organization's mission to a more neutral stance that power and status are at work in all of our interactions. The second trend that emerged was the tendency for participants to focus on agency-based explanations of power dynamics.

Nurses' Perceptions of Horizontal Violence.

In this article, I describe a study exploring horizontal violence and nurses' perceptions of the phenomenon within the context of two 28-bed inpatient hospital units. The purpose of the study was to develop a clearer understanding of horizontal violence, incorporating observation and inquiry to identify the language nurses use to describe their experiences and factors in the nursing work environment that may perpetuate the phenomenon. Observation, review and analysis of policies, and interviews with staff were completed between June and November 2012. Thematic analysis resulted in five themes: (a) behaviors are minimized and not recognized, (b) fear inhibits all reporting, (c) avoidance and isolation are coping strategies, (d) lack of respect and support, and (e) organizational chaos. The findings suggest future interventions must address a range of factors that perpetuate horizontal violence within the nursing work environment with consideration for the embeddedness and complexity of the phenomenon.

Feasibility of Computed Tomography in a Multicenter COPD Trial: A Study of the Effect of AZD9668 on Structural Airway Changes.

INTRODUCTION: The aim of this study was to establish the feasibility of using computed tomography (CT) in a multicenter setting to assess structural airway changes. METHODS: This was a 12-week, randomized, double-blind, placebo-controlled, Phase IIb trial using CT to investigate the effect of a novel, oral, reversible neutrophil elastase inhibitor, AZD9668 60 mg twice daily (BID), on structural airway changes in patients aged 50-80 years with chronic obstructive pulmonary disease (COPD) (ex-smokers). PRIMARY OUTCOME VARIABLE: airway wall thickness at an extrapolated interior perimeter of 10 mm (AWT-Pi10). Secondary outcome variables: fifth-generation wall area %; air trapping index; pre- and post-bronchodilator forced expiratory volume in 1 s (FEV1); morning and evening peak expiratory flow and FEV1; body plethysmography; EXAcerbations of Chronic pulmonary disease Tool (EXACT); Breathlessness, Cough, and Sputum Scale (BCSS); St George's Respiratory Questionnaire for COPD; and proportion of reliever-medication-free trial days. Safety variables were also assessed. RESULTS: There was no difference between placebo (n = 19) and AZD9668 (n = 17) for AWT-Pi10 at treatment end. This was consistent with results for most secondary variables. However, patients randomized to AZD9668 experienced an improvement versus placebo for morning and evening FEV1, and EXACT and BCSS cough and sputum scores. AZD9668 60 mg BID was well tolerated and no new safety concerns were identified. CONCLUSIONS: This study confirmed the feasibility of using CT to assess structural airway changes in COPD. However, there was no evidence of improvements in CT structural measures following 12 weeks' treatment with AZD9668 60 mg BID. FUNDING: AstraZeneca.