Prevalence and clinical association of gene mutations through multiplex mutation testing in patients with NSCLC: results from the ETOP Lungscape Project.

Background: Reported prevalence of driver gene mutations in non-small-cell lung cancer (NSCLC) is highly variable and clinical correlations are emerging. Using NSCLC biomaterial and clinical data from the European Thoracic Oncology Platform Lungscape iBiobank, we explore the epidemiology of mutations and association to clinicopathologic features and patient outcome (relapse-free survival, time-to-relapse, overall survival). Methods: Clinically annotated, resected stage I-III NSCLC FFPE tissue was assessed for gene mutation using a microfluidics-based multiplex PCR platform. Mutant-allele detection sensitivity is >1% for most of the ∼150 (13 genes) mutations covered in the multiplex test. Results: Multiplex testing has been carried out in 2063 (76.2%) of the 2709 Lungscape cases (median follow-up 4.8 years). FFPE samples mostly date from 2005 to 2008, yet recently extracted DNA quality and quantity was generally good. Average DNA yield/case was 2.63 µg; 38 cases (1.4%) failed QC and were excluded from study; 95.1% of included cases allowed the complete panel of mutations to be tested. Most common were KRAS, MET, EGFR and PIK3CA mutations with overall prevalence of 23.0%, 6.8%, 5.4% and 4.9%, respectively. KRAS and EGFR mutations were significantly more frequent in adenocarcinomas: PIK3CA in squamous cell carcinomas. MET mutation prevalence did not differ between histology groups. EGFR mutations were found predominantly in never smokers; KRAS in current/former smokers. For all the above mutations, there was no difference in outcome between mutated and non-mutated cases. Conclusion: Archival FFPE NSCLC material is adequate for multiplex mutation analysis. In this large, predominantly European, clinically annotated stage I-III NSCLC cohort, none of the mutations characterized showed prognostic significance.

Frequent PD-L1 expression in testicular germ cell tumors.

BACKGROUND: Many testicular germ cell cancers are curable despite metastatic disease, but about 10-15% of patients fail cisplatin-based first-line treatment. Immunotherapy is considered as additional treatment approach for these patients. Inhibition of the interaction between Programmed Death Receptor 1 (PD-1) and Programmed Death Receptor Ligand 1 (PD-L1) enhances T-cell responses in vitro and mediates clinical antitumour activity. We analysed the expression of PD-L1 in testicular germ cell tumours to evaluate its potential as target for immunotherapeutic strategies. METHODS: Immunohistochemistry was performed in 479 formalin-fixed paraffin-embedded specimens using a rabbit monoclonal antibody (E1L3N). The tissue microarray consisted of 208 pure seminomas, 121 non-seminomas, 20 intratubular germ cell neoplasia unclassified (IGCNU) and 20 specimens of non-neoplastic testicular tissue. RESULTS: Programmed Death Receptor Ligand-1 expression was found in 73% of all seminomas and in 64% of all non-seminomas. None of 20 IGCNU and none of 20 normal tissue specimens exhibited PD-L1 expression. PD-L1 positive stromal cells were only detected in seminomas, but not in non-seminomas. The anti PD-L1 antibody showed a pre-dominantly membranous staining pattern in testicular tumour cells, as well as expression in stromal cells. CONCLUSIONS: This frequent expression of PD-L1 in human testicular germ cell tumours suggests that patients with testicular germ cell tumours could profit from immunotherapeutic strategies using anti-PD1 and anti-PDL1 antibodies.

Assessing communication skills in dietetic consultations: the development of the reliable and valid DIET-COMMS tool.

BACKGROUND: There is an increasing emphasis on the development of communication skills for dietitians but few evidence-based assessment tools available. The present study aimed to develop a dietetic-specific, short, reliable and valid assessment tool for measuring communication skills in patient consultations: DIET-COMMS. METHODS: A literature review and feedback from 15 qualified dietitians were used to establish face and content validity during the development of DIET-COMMS. In total, 113 dietetic students and qualified dietitians were video-recorded undertaking mock consultations, assessed using DIET-COMMS by the lead author, and used to establish intra-rater reliability, as well as construct and predictive validity. Twenty recorded consultations were reassessed by nine qualified dietitians to assess inter-rater reliability: eight of these assessors were interviewed to determine user evaluation. RESULTS: Significant improvements in DIET-COMMS scores were achieved as students and qualified staff progressed through their training and gained experience, demonstrating construct validity, and also by qualified staff attending a training course, indicating predictive validity (P < 0.05). An acceptable level of intra-rater reliability (rs  = 0.90) and a moderate level of inter-rater reliability (r = 0.49) were demonstrated. Interviews identified many positive features and possible uses for DIET-COMMS in both pre- and post-registration settings. The need for assessor training was emphasised and how readily qualified dietitians would accept assessment of skills in practice was questioned. DISCUSSION: DIET-COMMS is a short, user-friendly, reliable and valid tool for measuring communication skills in patient consultations with both pre- and post-registration dietitians. Additional work is required to develop a training package for assessors and to identify how DIET-COMMS assessment can acceptably be incorporated into practice.

'Everybody just thinks I'm weird': a qualitative exploration of the psychosocial experiences of adolescents with Tourette syndrome.

BACKGROUND: Research suggests Tourette syndrome (TS) can have a negative impact on quality of life. To date, little research has examined the perspectives of young people with this condition in depth. METHODS: Six 14- to 16-year-olds with TS took part in semi-structured interviews to explore the perceived impact of this condition on self and on relationships with others. The transcripts were analysed using interpretative phenomenological analysis. RESULTS: The young people felt that TS was a constant presence in their lives, but one they have learnt to cope with well. Most had developed supportive friendships but encountered problems when interacting with the wider peer network. Specific concerns around meeting new people and future employment were voiced. CONCLUSIONS: The adolescents described specific ways in which TS affects quality of life and social interactions, and the effort it can take to cope effectively with this condition.

TTF1 expression in non-small cell lung carcinoma: association with TTF1 gene amplification and improved survival.

Acquired chromosomal aberrations play an important role in tumour development and progression. Such genetic alterations occur in a significant proportion of non-small cell lung carcinomas (NSCLCs) and include amplification of 14q13.3, which contains the TTF1 gene. We asked whether TTF1 amplification is associated with increased TTF1 protein expression in NSCLCs, and whether TTF1 is associated with clinicopathological features, including patient survival. We used a FISH assay and quantitative immunohistochemical staining to interrogate a population-based cohort of 538 NSCLCs from Swiss patients for TTF1 amplification and protein expression. We found TTF1 amplification in approximately 13% of adenocarcinomas (ACs) and in approximately 9% of squamous cell carcinomas (SCCs) and TTF1 amplification was associated with increased TTF1 protein expression. High-level TTF1 expression was significantly associated with smaller tumour size, female gender and longer overall survival only among ACs (median survival 82 versus 28 months; p = 0.002). On multivariate analysis, high TTF1 expression was an independent predictor of favourable prognosis in patients with AC [hazard ratio, 0.56 (95% CI 0.38-0.83); p = 0.008]. We conclude that TTF1 amplification is a mechanism of high-level TTF1 expression in a subset of NSCLCs. When expressed at high levels, this routinely used diagnostic marker is also an independent biomarker of favourable prognosis in AC.

Qualitative research in nutrition and dietetics: getting started.

Qualitative research is well placed to answer complex questions about food-related behaviour because it investigates how and why individuals act in certain ways. The field of qualitative health research is undoubtedly gaining momentum and, increasingly, there is a recognition that it should be a vital part of the decision-making processes that direct the development of health policy and practice. Much of the guidance available, however, is difficult to navigate for those new to 'qualitative research', and there is little discussion of qualitative research issues specifically in relation to nutrition and dietetics. This review, the first in a series, outlines the field of qualitative enquiry, its potential usefulness in nutrition and dietetics, and how to embark upon this type of research. Furthermore, it describes a process to guide high-quality qualitative research in this area that proceeds from the research question(s) and considers the key philosophical assumptions about ontology, epistemology and methodology that underpin the overall design of a study. Other reviews in this series provide an overview of the principal techniques of data collection and sampling, data analysis, and quality assessment of qualitative work, and provide some practical advice relevant to nutrition and dietetics, along with glossaries of key terms.

Communication skills for behaviour change in dietetic consultations.

BACKGROUND: Both the UK's National Health Service (NHS) and the National Institute of health and Clinical Excellence (NICE) have recommended increased training for health professionals in communication skills. There is evidence to suggest that communication skills are important in helping people to change health-related behaviour, which is a key role for dietitians. This study investigated the views of UK dietitians about their training needs and experience in relation to communication skills in dietetic practice. METHODS: In October 2007, a cross-sectional survey was mailed to all British Dietetic Association members (n = 6013). The survey gathered quantitative data and free-text comments to ascertain the level, type and effect of communication skills training received by dietitians at both the pre- and post-registration level. RESULTS: There were 1158 respondents; a response rate of 19.3%. Ninety-eight percent (n = 1117) rated communication skills as either very or extremely important in client consultations. Post-registration training had been undertaken by 73% (n = 904). Of these, over 90% of respondents perceived that post-registration training had led to improvements in their relationships with patients, their confidence in client interviews and their ability to cope with challenging clients. However, 248 (21.4%) felt time keeping in interviews had worsened. Lack of time for client interviews was also the most commonly identified barrier (19%, n = 216) to implementing the skills. CONCLUSIONS: This study has explored an important and under-researched area. Respondents strongly endorsed the importance of good communication skills and the benefits of post-registration training in this area. Some felt that good communication was time consuming but others felt that time management had improved. Further research and training is required to support the implementation of these skills into dietetic practice.

Evaluating veterinary practitioner perceptions of communication skills and training.

A survey was conducted among veterinary practitioners in the UK and the USA in 2012/2013. Thematic analysis was used to identify underlying reasons behind answers to questions about the importance of communication skills and the desire to participate in postgraduate communication skills training. Lack of training among more experienced veterinary surgeons, incomplete preparation of younger practitioners and differences in ability to communicate all contribute to gaps in communication competency. Barriers to participating in further communication training include time, cost and doubts in the ability of training to provide value. To help enhance communication ability, communication skills should be assessed in veterinary school applicants, and communication skills training should be more thoroughly integrated into veterinary curricula. Continuing education/professional development in communication should be part of all postgraduate education and should be targeted to learning style preferences and communication needs and challenges through an entire career in practice.

Mental health problems and social supports among homeless mothers and children victims of domestic and community violence.

BACKGROUND: Children and mothers who have suffered domestic or neighbourhood violence constitute a high risk group, although it has not been clear whether their mental health needs are specifically related to the type of violence. This paper reports on the prevalence of mental health problems in homeless parents and children who have experienced domestic and neighbourhood violence and their access to social support networks. METHODS: Three groups of families who had become homeless were compared: those experiencing domestic violence (48 with 75 children), victims of neighbourhood violence (14 with 29 children), and those who became homeless for other reasons (31 with 54 children). Mothers completed a service use semi-structured interview, the Strengths and Difficulties Questionnaire, the General Health Questionnaire, the Family Support Scales, and the SF-36 Health Status Questionnaire. RESULTS: Levels of psychiatric morbidity were high in the group experiencing domestic violence (35.7% in children and 21.9% in mothers) and higher still in those who were victims of neighbourhood violence (52.2% in children and 50% in mothers). Levels of social support were found to be an important factor, particularly in relation to professional support and support from other family members, as they predicted both child and maternal psychopathology. CONCLUSIONS: Mental health interventions for victims of domestic and neighbourhood violence should be integrated with community programmes of social reintegration. Mental health professionals should work in close collaboration with Housing Departments, Social Services, Education and the Police.