Focused molecular analysis of small cell lung cancer: feasibility in routine clinical practice.

Background: There is an urgent need to identify molecular signatures in small cell lung cancer (SCLC) that may select patients who are likely to respond to molecularly targeted therapies. In this study, we investigate the feasibility of undertaking focused molecular analyses on routine diagnostic biopsies in patients with SCLC.

Methods: A series of histopathologically confirmed formalin-fixed, paraffin-embedded SCLC specimens were analysed for epidermal growth factor receptors (EGFR), KRAS, NRAS and BRAF mutations, ALK gene rearrangements and MET amplification. EGFR and KRAS mutation testing was evaluated using real time polymerase chain reaction (RT-PCR cobas®), BRAF and NRAS mutations using multiplex PCR and capillary electrophoresis-single strand conformation analysis, and ALK and MET aberrations with fluorescent in situ hybridization. All genetic aberrations detected were validated independently.

Results: A total of 105 patients diagnosed with SCLC between July 1990 and September 2006 were included. 60 (57 %) patients had suitable tumour tissue for molecular testing. 25 patients were successfully evaluated for all six pre-defined molecular aberrations. Eleven patients failed all molecular analysis. No mutations in EGFR, KRAS and NRAS were detected, and no ALK gene rearrangements or MET gene amplifications were identified. A V600E substitution in BRAF was detected in a Caucasian male smoker diagnosed with SCLC with squamoid and glandular features.

Conclusion: The paucity of patients with sufficient tumour tissue, quality of DNA extracted and low frequency of aberrations detected indicate that alternative molecular characterisation approaches are necessary, such as the use of circulating plasma DNA in patients with SCLC.

IMPLEMENTING BACK PAIN TREATMENT PATHWAYS IN CLINICAL PRACTICE: QUALITATATIVE ANALYSIS OF STAKEHOLDER PERCEPTIONS

Background
Evidence-based practice advocates utilising best current research evidence, while reflecting patient preference and clinical expertise in decision making. Successfully incorporating this evidence into practice is a complex process. Based on recommendations of existing guidelines and systematic evidence reviews conducted using the GRADE approach, treatment pathways for common spinal pain disorders were developed.

Aims
The aim of this study was to identify important potential facilitators to the integration of these pathways into routine clinical practice.

Methods
A 22 person stakeholder group consisting of patient representatives, clinicians, researchers and members of relevant clinical interest groups took part in a series of moderated focus groups, followed up with individual, semi-structured interviews. Data were analysed using content analysis.

Results
Participants identified a number of issues which were categorized into broad themes. Common facilitators to implementation included continual education and synthesis of research evidence which is reflective of everyday practice; as well as the use of clear, unambiguous messages in recommendations. Meeting additional training needs in new or extended areas of practice was also recognized as an important factor. Different stakeholders identified specific areas which could be associated with successful uptake. Patients frequently defined early involvement in a shared decision making process as important. Clinicians identified case based examples and information on important prognostic indicators as useful tools to aiding decisions.

Conclusion
A number of potential implementation strategies were identified. Further work will examine the impact of these and other important factors on the integration of evidence-based treatment recommendations into clinical practice.

Naming the pain in requirements engineering: Contemporary problems, causes, and effects in practice

Requirements Engineering (RE) has received much attention in research and practice due to its importance to software project success. Its inter-disciplinary nature, the dependency to the customer, and its inherent uncertainty still render the discipline diffcult to investigate. This results in a lack of empirical data. These are necessary, however, to demonstrate which practically relevant RE problems exist and to what extent they matter. Motivated by this situation, we initiated the Naming the Pain in Requirements Engineering (NaPiRE) initiative which constitutes a globally distributed, bi-yearly replicated family of surveys on the status quo and problems in practical RE.

In this article, we report on the analysis of data obtained from 228 companies in 10 countries. We apply Grounded Theory to the data obtained from NaPiRE and reveal which contemporary problems practitioners encounter. To this end, we analyse 21 problems derived from the literature with respect to their relevance and criticality in dependency to their context, and we complement this picture with a cause-effect analysis showing the causes and effects surrounding the most critical problems.

Our results give us a better understanding of which problems exist and how they manifest themselves in practical environments. Thus, we provide a rst step to ground contributions to RE on empirical observations which, by now, were dominated by conventional wisdom only.

Hate crime legislation and violence against sex workers in Ireland: Lessons in Policy and Practice

Drawing on data from UglyMugs.ie (a reporting mechanism for sex workers) this paper considers whether crimes against sex workers should be considered as hate crimes. In many ways, the debates around hate crime in the UK are more developed than in Ireland. As yet the Irish State has yet to criminalise the ‘hate’ element of crime and has been severely criticised for its relatively lacklustre approach to recording incidents of bias or hate crimes against certain social groups. The paper adopts the structural understanding of hate crime espoused by Barbara Perry (2001) who frames the dynamics of hate crime within a complex interplay of political, social and cultural factors. In our analysis we consider what is termed ‘whorephobia’ through the ambit of criminalisation and stigmatisation, gender and heteronormativity in Irish society, and the gendered nature of policing in both parts of Ireland.

Inverse Association Between Gluteofemoral Obesity and Risk of Barrett's Esophagus in a Pooled Analysis

BACKGROUND & AIMS: Gluteofemoral obesity (determined by measurement of subcutaneous fat in hip and thigh regions) could reduce risks of cardiovascular and diabetic disorders associated with abdominal obesity. We evaluated whether gluteofemoral obesity also reduces risk of Barrett's esophagus (BE), a premalignant lesion associated with abdominal obesity.

METHODS: We collected data from non-Hispanic white participants in 8 studies in the Barrett's and Esophageal Adenocarcinoma Consortium. We compared measures of hip circumference (as a proxy for gluteofemoral obesity) from cases of BE (n=1559) separately with 2 control groups: 2557 population-based controls and 2064 individuals with gastroesophageal reflux disease (GERD controls). Study-specific odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using individual participant data and multivariable logistic regression and combined using random effects meta-analysis.

RESULTS: We found an inverse relationship between hip circumference and BE (OR per 5 cm increase, 0.88; 95% CI, 0.81-0.96), compared with population-based controls in a multivariable model that included waist circumference. This association was not observed in models that did not include waist circumference. Similar results were observed in analyses stratified by frequency of GERD symptoms. The inverse association with hip circumference was only statistically significant among men (vs population-based controls: OR, 0.85; 95% CI, 0.76-0.96 for men; OR, 0.93; 95% CI, 0.74-1.16 for women). For men, within each category of waist circumference, a larger hip circumference was associated with decreased risk of BE. Increasing waist circumference was associated with increased risk of BE in the mutually adjusted population-based and GERD control models.

CONCLUSIONS: Although abdominal obesity is associated with increased risk of BE, there is an inverse association between gluteofemoral obesity and BE, particularly among men.

Applied behavior analysis: What do teachers of students with autism spectrum disorder know?

With rising numbers of school-aged children with autism educated in mainstream classroomsand applied behavior analysis (ABA) considered the basis of best practice, teachers’ knowledgein this field has become a key concern for inclusion. Self-reported knowledge of ABA of specialneeds teachers (n=165) was measured and compared to their actual knowledge of ABAdemonstrated in accurate responses to a multiple-choice test. Findings reported here show thatteachers’ self-perceived knowledge exceeded actual knowledge and that actual knowledge ofABA was not

Sports coaching and the law of negligence: implications for coaching practice

The ordinary principles of the law of negligence are applicable in the context of sport, including claims brought against volunteer and professional coaches. Adopting the perspective of the coach, this article intends to raise awareness of the emerging intersection between the law of negligence and sports coaching, by utilising an interdisciplinary analysis designed to better safeguard and reassure coaches mindful of legal liability. Detailed scrutiny of two cases concerning alleged negligent coaching, with complementary discussion of some of the ethical dilemmas facing modern coaches, reinforces the legal duty and obligation of all coaches to adopt objectively reasonable and justifiable coaching practices when interacting with athletes. Problematically, since research suggests that some coaching practice may be underpinned by “entrenched legitimacy” and “uncritical inertia”, it is argued that coach education and training should place a greater emphasis on developing a coach’s awareness and understanding of the evolving legal context in which they discharge the duty of care incumbent upon them.

How can we use systematic reviews to inform clinical practice?

Aims/purpose: Systematic reviews provide the highest quality evidence and inform clinical practice. For patient benefit, it is imperative that nurses keep abreast of evidence-based practice. This presentation highlights where to find systematic reviews and how the information presented can be used to inform care.
Presentation description: Clinical research is increasing at an incredible rate. In the clinical trials database alone, more than 2000 new studies are registered/month and this does not include qualitative studies that do not require registration. Keeping abreast of current evidence can not only be a time consuming process, but can be problematic when studies produce conflicting results. Systematic reviews can be useful for summarizing the increasing amount of knowledge that is gained from scientific papers. In addition, combining individual studies in a meta-analysis increases statistical power, resulting in more precise effect estimates. This presentation draws upon a few systematic reviews relevant to ICU nursing practice, highlights their findings and demonstrates how the information can be used to inform translation of evidence into practice. Additionally, although these reviews include steps to minimize bias, nurses should be aware of some of the biases that may reduce confidence in the findings.
Conclusion: Systematic reviews can be useful tools for informing evidence based practice, although careful interpretation is necessary for understanding their relevance to local practice.

ERIC recommendations on TP53 mutation analysis in chronic lymphocytic leukemia.

Recent evidence suggests that - in addition to 17p deletion - TP53 mutation is an independent prognostic factor in chronic lymphocytic leukemia (CLL). Data from retrospective analyses and prospective clinical trials show that ∼5% of untreated CLL patients with treatment indication have a TP53 mutation in the absence of 17p deletion. These patients have a poor response and reduced progression-free survival and overall survival with standard treatment approaches. These data suggest that TP53 mutation testing warrants integration into current diagnostic work up of patients with CLL. There are a number of assays to detect TP53 mutations, which have respective advantages and shortcomings. Direct Sanger sequencing of exons 4-9 can be recommended as a suitable test to identify TP53 mutations for centers with limited experience with alternative screening methods. Recommendations are provided on standard operating procedures, quality control, reporting and interpretation. Patients with treatment indications should be investigated for TP53 mutations in addition to the work-up recommended by the International workshop on CLL guidelines. Patients with TP53 mutation may be considered for allogeneic stem cell transplantation in first remission. Alemtuzumab-based regimens can yield a substantial proportion of complete responses, although of short duration. Ideally, patients should be treated within clinical trials exploring new therapeutic agents.

Ethical reasoning through simulation: a phenomenological analysis of student experience

Background
Medical students transitioning into professional practice feel underprepared to deal with the emotional complexities of real-life ethical situations. Simulation-based learning (SBL) may provide a safe environment for students to probe the boundaries of ethical encounters. Published studies of ethics simulation have not generated sufficiently deep accounts of student experience to inform pedagogy. The aim of this study was to understand students’ lived experiences as they engaged with the emotional challenges of managing clinical ethical dilemmas within a SBL environment.

Methods
This qualitative study was underpinned by an interpretivist epistemology. Eight senior medical students participated in an interprofessional ward-based SBL activity incorporating a series of ethically challenging encounters. Each student wore digital video glasses to capture point-of-view (PoV) film footage. Students were interviewed immediately after the simulation and the PoV footage played back to them. Interviews were transcribed verbatim. An interpretative phenomenological approach, using an established template analysis approach, was used to iteratively analyse the data.

Results
Four main themes emerged from the analysis: (1) ‘Authentic on all levels?’, (2)‘Letting the emotions flow’, (3) ‘Ethical alarm bells’ and (4) ‘Voices of children and ghosts’. Students recognised many explicit ethical dilemmas during the SBL activity but had difficulty navigating more subtle ethical and professional boundaries. In emotionally complex situations, instances of moral compromise were observed (such as telling an untruth). Some participants felt unable to raise concerns or challenge unethical behaviour within the scenarios due to prior negative undergraduate experiences.

Conclusions
This study provided deep insights into medical students’ immersive and embodied experiences of ethical reasoning during an authentic SBL activity. By layering on the human dimensions of ethical decision-making, students can understand their personal responses to emotion, complexity and interprofessional working. This could assist them in framing and observing appropriate ethical and professional boundaries and help smooth the transition into clinical practice.