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Allogeneic haematopoietic cell transplantation (HCT) replaces the stem cells responsible for blood production with those harvested from a donor, and is received by 40,000 patients worldwide each year. To quantify dynamics of long-term stem cell engraftment, we sequenced whole genomes of 2,824 single-cell-derived haematopoietic colonies from blood samples of 10 donor-recipient pairs taken 9-31 years after HLA-matched sibling HCT. With younger donors, 10,000–50,000 stem cells had engrafted and were still contributing to haematopoiesis at time of sampling, but estimates were 10-fold lower with older donors. Engrafted stem cells made multilineage contributions to myeloid, B-lymphoid and T-lymphoid populations, although individual clones often showed biases towards one or other mature cell type. Recipients had lower clonal diversity than matched donors, equivalent to ~10-15 years of additional ageing, arising from up to 25-fold greater expansion of stem cell clones. An HCT-related population bottleneck alone could not explain these differences: instead, phylogenetic trees evinced two distinct modes of HCT-specific selection. In ‘pruning selection’, cell divisions underpinning recipient-enriched clonal expansions had occurred in the donor, preceding transplant – their selective advantage derived from preferential mobilisation, harvest, survival ex vivo or initial homing. In ‘growth selection’, cell divisions underpinning clonal expansion occurred through proliferative advantage in the recipient’s marrow after homing – clones with multiple driver mutations especially demonstrated this pattern. Uprooting stem cells from their native environment and transplanting them to foreign soil exaggerates selective pressures, distorting and accelerating the loss of clonal diversity compared to the unperturbed haematopoiesis of donors.

The rates and patterns of somatic mutation in normal tissues are largely unknown outside of humans1–7. Comparative analyses can shed light on the diversity of mutagenesis across species, and on long-standing hypotheses about the evolution of somatic mutation rates and their role in cancer and ageing. Here we performed whole-genome sequencing of 208 intestinal crypts from 56 individuals to study the landscape of somatic mutation across 16 mammalian species. We found that somatic mutagenesis was dominated by seemingly endogenous mutational processes in all species, including 5-methylcytosine deamination and oxidative damage. With some differences, mutational signatures in other species resembled those described in humans8, although the relative contribution of each signature varied across species. Notably, the somatic mutation rate per year varied greatly across species and exhibited a strong inverse relationship with species lifespan, with no other life-history trait studied showing a comparable association. Despite widely different life histories among the species we examined—including variation of around 30-fold in lifespan and around 40,000-fold in body mass—the somatic mutation burden at the end of lifespan varied only by a factor of around 3. These data unveil common mutational processes across mammals, and suggest that somatic mutation rates are evolutionarily constrained and may be a contributing factor in ageing.

Organoid cell culture methodologies are enabling the generation of cell models from healthy and diseased tissue. Patient-derived cancer organoids that recapitulate the genetic and histopathological diversity of patient tumours are being systematically generated, providing an opportunity to investigate novel cancer biology and therapeutic approaches. The use of organoid cultures for many applications, including genetic and chemical perturbation screens, is limited due to the technical demands and cost associated with their handling and propagation. Here we report and benchmark a suspension culture technique for cancer organoids which allows for the expansion of models to tens of millions of cells with increased efficiency in comparison to standard organoid culturing protocols. Using whole-genome DNA and RNA sequencing analyses, as well as medium-throughput drug sensitivity testing and genome-wide CRISPR-Cas9 screening, we demonstrate that cancer organoids grown as a suspension culture are genetically and phenotypically similar to their counterparts grown in standard conditions. This culture technique simplifies organoid cell culture and extends the range of organoid applications, including for routine use in large-scale perturbation screens.

BackgroundHepatitis C virus (HCV) infection is a key cause of liver disease but can be cured in more than 95% of patients. Around 70 000 people in England may have undiagnosed HCV infection and many more will not have been treated. Interventions to increase case-finding in primary care are likely to be cost-effective; however, evidence of effective interventions is lacking. The Hepatitis C Assessment Through to Treatment (HepCATT) trial assessed whether a complex intervention in primary care could increase case-finding, testing, and treatment of HCV.AimTo investigate the feasibility and acceptability of the HepCATT intervention.Design and settingA qualitative study with primary care practice staff from practices in the south west of England taking part in the HepCATT trial.MethodSemi-structured interviews were carried out with GPs, nurses, and practice staff to ascertain their views of the HepCATT intervention at least 1 month after implementing the intervention in their practice. Normalisation process theory, which outlines the social processes involved in intervention implementation, informed thematic data analysis.ResultsParticipants appreciated the HepCATT intervention for increasing knowledge and awareness of HCV. Although some initial technical difficulties were reported, participants saw the benefits of using the audit tool to systematically identify patients with HCV infection risk factors and found it straightforward to use. Participants valued the opportunity to discuss HCV testing with patients, especially those who may not have been previously aware of HCV risk. Future implementation should consider fully integrating software systems and additional resources to screen patient lists and conduct tests.ConclusionWhen supported by a complex intervention, primary care can play a crucial role in identifying and caring for patients with HCV infection, to help stem the HCV epidemic, and prevent HCV-related illness.

BackgroundImplant-based breast reconstruction (IBBR) is the most commonly performed reconstructive procedure following mastectomy. IBBR techniques are evolving rapidly, with mesh-assisted subpectoral reconstruction becoming the standard of care and more recently, prepectoral techniques being introduced. These muscle-sparing techniques may reduce postoperative pain, avoid implant animation and improve cosmetic outcomes and have been widely adopted into practice. Although small observational studies have failed to demonstrate any differences in the clinical or patient-reported outcomes of prepectoral or subpectoral reconstruction, high-quality comparative evidence of clinical or cost-effectiveness is lacking. A well-designed, adequately powered randomised controlled trial (RCT) is needed to compare the techniques, but breast reconstruction RCTs are challenging. We, therefore, aim to undertake an external pilot RCT (Best-BRA) with an embedded QuinteT Recruitment Intervention (QRI) to determine the feasibility of undertaking a trial comparing prepectoral and subpectoral techniques.Methods and analysisBest-BRA is a pragmatic, two-arm, external pilot RCT with an embedded QRI and economic scoping for resource use. Women who require a mastectomy for either breast cancer or risk reduction, elect to have an IBBR and are considered suitable for both prepectoral and subpectoral reconstruction will be recruited and randomised 1:1 between the techniques.The QRI will be implemented in two phases: phase 1, in which sources of recruitment difficulties are rapidly investigated to inform the delivery in phase 2 of tailored interventions to optimise recruitment of patients.Primary outcomes will be (1) recruitment of patients, (2) adherence to trial allocation and (3) outcome completion rates. Outcomes will be reviewed at 12 months to determine the feasibility of a definitive trial.Ethics and disseminationThe study has been approved by the National Health Service (NHS) Wales REC 6 (20/WA/0338). Findings will be presented at conferences and in peer-reviewed journals.Trial registration numberISRCTN10081873.

Background: parents commonly ask about food allergy tests, to find a cause for their child's eczema, yet the value of routine testing is uncertain. Objective: To determine whether a clinical trial comparing test-guided dietary advice versus usual care, for the management of eczema, is feasible. Methods: children (>3 months and Results: from 1059 invitation letters sent to carers of potentially eligible children, 84 were randomized (42 per group) with mean age of 32.4 months (SD 13.9) and POEM of 8.7 (4.8). Of the 42, 6 (14%) intervention participants were advised to exclude one or more foods, most commonly egg, peanut or milk. By participant, 1/6 had an oral food challenge (negative); 3/6 were told to exclude until review in allergy clinic; and 6/6 advised a home dietary trial (exclusion and reintroduction of food over 4–6 weeks) – with 1/6 partially completing it. Participant retention (four withdrawals) and data completeness (74%–100%) were acceptable and contamination low (two usual care participants had allergy tests). There were three minor SPT-related adverse events. During follow-up, 12 intervention and 8 usual care participants had minor, unrelated adverse events plus one unrelated hospital admission. Conclusions: it is possible to recruit, randomize and retain children with eczema from primary care into a trial of food allergy screening and to collect the outcomes of interest. Changes to recruitment and inclusion criteria are needed in a definitive trial, to ensure inclusion of younger children from more diverse backgrounds.

Objective To evaluate the effectiveness and cost effectiveness of a complex intervention in primary care that aims to increase uptake of hepatitis C virus (HCV) case finding and treatment. Design Pragmatic, two armed, practice level, cluster randomised controlled trial and economic evaluation. Setting and participants 45 general practices in South West England (22 randomised to intervention and 23 to control arm). Outcome data were collected from all intervention practices and 21/23 control practices. Total number of flagged patients was 24 473 (about 5% of practice list). Intervention Electronic algorithm and flag on practice systems identifying patients with HCV risk markers (such as history of opioid dependence or HCV tests with no evidence of referral to hepatology), staff educational training in HCV, and practice posters/leaflets to increase patients’ awareness. Flagged patients were invited by letter for an HCV test (with one follow-up) and had on-screen pop-ups to encourage opportunistic testing. The intervention lasted one year, with practices recruited April to December 2016. Main outcome measures Primary outcome: uptake of HCV testing. Secondary outcomes: number of positive HCV tests and yield (proportion HCV positive); HCV treatment assessment at hepatology; cost effectiveness. Results Baseline HCV testing of flagged patients (six months before study start) was 608/13 097 (4.6%) in intervention practices and 380/11 376 (3.3%) in control practices. During the study 2071 (16%) of flagged patients in the intervention practices and 1163 (10%) in control practices were tested for HCV: overall intervention effect as an adjusted rate ratio of 1.59 (95% confidence interval 1.21 to 2.08; Pv 4.4%; adjusted risk ratio 1.40, 0.99 to 1.95). Referral and assessment increased in intervention practices compared with control practices (adjusted rate ratio 5.78, 1.6 to 21.6) with a risk difference of 1.3 per 1000 and a “number needed to help” of one extra HCV diagnosis, referral, and assessment per 792 (95% confidence interval 558 to 1883) patients flagged. The average cost of HCV case finding was £4.03 (95% confidence interval £2.27 to £5.80) per at risk patient and £3165 per additional patient assessed at hepatology. The incremental cost effectiveness ratio was £5783 per quality adjusted life year (QALY), with 93.3% probability of being below £20 000 per QALY. Conclusion HepCATT had a modest impact but is a low cost intervention that merits optimisation and implementation as part of an NHS strategy to increase HCV testing and treatment. Trial registration ISRCTN61788850.

BackgroundLarge animal models of human neurological disorders are advantageous compared to rodent models due to their neuroanatomical complexity, longevity and their ability to be maintained in naturalised environments. Some large animal models spontaneously develop behaviours that closely resemble the symptoms of neural and psychiatric disorders. The horse is an example of this; the domestic form of this species consistently develops spontaneous stereotypic behaviours akin to the compulsive and impulsive behaviours observed in human neurological disorders such as Tourette’s syndrome. The ability to non-invasively probe normal and abnormal equine brain function through cognitive testing may provide an extremely useful methodological tool to assess brain changes associated with certain human neurological and psychiatric conditions.New methodAn automated operant system with the ability to present visual and auditory stimuli as well as dispense salient food reward was developed. To validate the system, ten horses were trained and tested using a standard cognitive task (three choice serial reaction time task (3-CSRTT)).ResultsAll animals achieved total learning criterion and performed six probe sessions. Learning criterion was met within 16.30 ± 0.79 sessions over a three day period. During six probe sessions, level of performance was maintained at 80.67 ± 0.57% (mean ± SEM) accuracy.Comparison with existing method(s)This is the first mobile fully automated system developed to examine cognitive function in the horse.ConclusionsA fully-automated operant system for mobile cognitive function of a large animal model has been designed and validated. Horses pose an interesting complementary model to rodents for the examination of human neurological dysfunction.

Stereotypic behaviors are commonly observed in domestic equids as they are in a range of captive nondomesticated species. Estimates suggest that 19.5%-32.5% of horses perform a stereotypy. The presence of these behaviors is thought to indicate suboptimal welfare status and can result in secondary physical pathologies, such as colic, ligament strain, and incisor wear. Relatively little is understood about the etiologies of oral and locomotor stereotypies. Seemingly disparate causal factors have been proposed, including gastric pathology, neural adaptation, and genetic predisposition. In this review, we propose a model of causality that presents separate pathways to the development and continuation of oral behaviors such as crib-biting, compared with locomotor alternatives (i.e., weaving). The word stereotypy has alarmingly negative connotation among horse keepers. Stereotypic behaviors are often viewed as vices, and therefore, a number of horse owners and establishments attempt to physically prevent the behavior with harsh mechanical devices. Such interventions can result in chronic stress and be further detrimental to equine welfare. Stereotypy has been proposed to be a stress coping mechanism. However, firm evidence of coping function has proven elusive. This review will explore management options directed at both prophylaxis and remediation.

Equitation encompasses a range of activities in which horses interact closely with humans. The need to ensure both horse management and equitation practice is ethical and sustainable is becoming emphasized globally. Robust and rigorous measurement is critical to objective assessment of practice. This review describes the outcomes of technology application within generic equine science and specific equitation science studies including heart rate monitoring, electromyography, infrared thermography, pressure algometry and remote recording of behaviour and cognitive functioning. The impact of pressure and tension applied by saddles, girths, head gear and gadgets is considered along with subtle behavioural measurements such as eye blink rate, behavioural switching and laterality, some of which reveal aspects brain functioning that have direct relevance to training. Well designed, reliable technology certainly has the potential to provide researchers with a panacea to problems relating to accuracy, precision and experimenter bias, ushering in a ‘golden age of equitation’. However, to reach this stage careful consideration must be given to experimental logistics such as sample selection, device calibration and data processing. A series of potential drawbacks with the use of Technology are identified including managing noise and increasing signal strength, dealing with practical implementation issues and managing the volume of data in order to conduct appropriate analysis to reach meaningful conclusions. Technology users are warned against the temptation to engage in Abductive Science when discussing the output of equitation science methodologies. Putting good research into practice, and vice versa, is crucial to future-proofing equitation and horse welfare.

BackgroundEarly onset eczema is associated with food allergy, and allergic reactions to foods can cause acute exacerbations of eczema. Parents often pursue dietary restrictions as a way of managing eczema and seek allergy testing for their children to guide dietary management. However, it is unclear whether test-guided dietary management improves eczema symptoms, and whether the practice causes harm through reduced use of conventional eczema treatment or unnecessary dietary restrictions. The aim of the Trial of Eczema allergy Screening Tests Study is to determine the feasibility of conducting a trial comparing food allergy testing and dietary advice versus usual care, for the management of eczema in children.Methods and analysisDesign: A single centre, two-group, individually randomised, feasibility randomised controlled trial (RCT) with economic scoping and a nested qualitative study. Setting: General Practioner (GP) surgeries in the west of England. Participants: children aged over 3 months and less than 5 years with mild to severe eczema. Interventions: allergy testing (structured allergy history and skin prick tests) or usual care. Sample size and outcome measures: we aim to recruit 80 participants and follow them up using 4-weekly questionnaires for 24 weeks. Nested qualitative study: We will conduct ~20 interviews with parents of participating children, 5–8 interviews with parents who decline or withdraw from the trial and ~10 interviews with participating GPs. Economic scoping: We will gather data on key costs and outcomes to assess the feasibility of carrying out a cost-effectiveness analysis in a future definitive trial.Ethics and disseminationThe study has been reviewed by the Health Research Authority and given a favourable opinion by the NHS REC (West Midlands – South Birmingham Research Ethics Committee, Reference Number 18/WM/0124). Findings will be submitted for presentation at conferences and written up for publication in peer-reviewed journals, which may include mixed-method triangulation and integration of the quantitative and qualitative findings.Trial registrationISRCTN15397185; Pre-results.

AimTo explore parent and general practitioner (GP) understanding and beliefs about food allergy testing for children with eczema.Design and settingQualitative interview study in UK primary care within the Trial of Eczema allergy Screening Tests feasibility trial.ParticipantsSemi-structured interviews with parents of children with eczema taking part in the feasibility study and GPs at practices hosting the study.Results21 parents and 11 GPs were interviewed. Parents discussed a range of potential causes for eczema, including a role for food allergy. They believed allergy testing to be beneficial as it could potentially identify a cure or help reduce symptoms and they found negative tests reassuring, suggesting to them that no dietary changes were needed. GPs reported limited experience and uncertainty regarding food allergy in children with eczema. While some GPs believed referral for allergy testing could be appropriate, most were unclear about its utility. They thought it should be reserved for children with severe eczema or complex problems but wanted more information to advise parents and help guide decision making.ConclusionsParents’ motivations for allergy testing are driven by the desire to improve their child’s condition and exclude food allergy as a possible cause of symptoms. GPs are uncertain about the role of allergy testing and want more information about its usefulness to support parents and help inform decision making.Trial registration numberISRCTN15397185.

Background: The ELCID (Early Lung Cancer Investigation and Diagnosis) trial was a feasibility randomised controlled trial examining the effect on lung cancer diagnosis of lowering the threshold for referral for urgent chest x-ray for smokers and recent ex-smokers, aged over 60 years with new chest symptoms. The qualitative component aimed to explore the feasibility of individually randomising patients to an urgent chest x-ray or not and to investigate any barriers to patient recruitment and participation. We integrated this within the feasibility trial to inform the design of any future definitive trial, particularly in view of the lack of research exploring symptomatic patients’ experiences of participating in diagnostic trials for possible/suspected lung cancer. Although previous studies contributed valuable information concerning screening for lung cancer and patient participation in trials, this paper is the first to explore issues relating to this specific patient group.\ud \ud \ud \ud Methods: Qualitative interviews were conducted with 21 patients, comprising 9 who had been randomised to receive an immediate chest x-ray, 10 who were randomised to receive the standard treatment according to the National Institute for Health and Care Excellence guidelines, and 2 who chose not to participate in the trial. Interviews were analysed using a framework approach.\ud \ud \ud \ud Results: The findings of this analysis showed that altruism, personal benefit and the reassurance of not having lung cancer were important factors in patient participation. However, patients largely believed that being in the intervention arm was more beneficial, highlighting a lack of understanding of clinical equipoise. Disincentives to participation in the trial included the stigmatisation of patients who smoked (given the inclusion criteria). Although the majority of patients reported that they were happy with the trial design, there was evidence of poor understanding. Last, for several patients, placing trust in health professionals was preferred to understanding the trial processes.\ud \ud \ud \ud Conclusions: The integration of a qualitative study focusing on participant experience as a secondary outcome of a feasibility trial enabled exploration of patient response to participation and recruitment. The study demonstrated that although it is feasible to recruit patients to the ELCID trial, more work needs to be done to ensure an understanding of study principles and also of smoking stigmatisation.\ud \ud \ud \ud Trial registration: ClinicalTrials.gov, NCT01344005. Registered on 27 April 2011.

BACKGROUND: Achieving earlier stage diagnosis is one option for improving lung cancer outcomes in the United Kingdom. Patients with lung cancer typically present with symptoms to general practitioners several times before referral or investigation. METHODS: We undertook a mixed methods feasibility individually randomised controlled trial (the ELCID trial) to assess the feasibility and inform the design of a definitive, fully powered, UK-wide, Phase III trial of lowering the threshold for urgent investigation of suspected lung cancer. Patients over 60, with a smoking history, presenting with new chest symptoms to primary care, were eligible to be randomised to intervention (urgent chest X-ray) or usual care. RESULTS: The trial design and materials were acceptable to GPs and patients. We randomised 255 patients from 22 practices, although the proportion of eligible patients who participated was lower than expected. Survey responses (89%), and the fidelity of the intervention (82% patients X-rayed within 3 weeks) were good. There was slightly higher anxiety and depression in the control arm in participants aged >75. Three patients (1.2%) were diagnosed with lung cancer. CONCLUSIONS: We have demonstrated the feasibility of individually randomising patients at higher risk of lung cancer, to a trial offering urgent investigation or usual care.British Journal of Cancer advance online publication 10 January 2017; doi:10.1038/bjc.2016.414 www.bjcancer.com.

OBJECTIVES: Treatment options for rheumatoid arthritis (RA) include conventional synthetic disease-modifying antirheumatic drugs (sDMARDs) and newer biologic DMARDs (biologics). This study describes treatment patterns, adherence to guidance and outcomes at hospital/regional level in the UK. METHODS: This was a retrospective cohort study of RA patients selected from six health regions and from four hospitals in each region, including at least one major teaching hospital and two to three district/general hospitals. Treatment with sDMARDs/biologics was examined between November 2009 and June 2010 in comparison with National Institute for Health and Clinical Excellence (NICE) guidance and in relation to disease activity. RESULTS: NICE guidance focuses on initiation of therapy and recommends combination sDMARD/biologic therapy. Analysis of 588 patient records indicates that overall 23% of patients were receiving biologic monotherapy. NICE guidance recommends initiation of biologics in patients with active RA (DAS28 >5.1): average DAS28 score on initiation of biologic therapy was above six in all regions. Range of DAS28 improvement post-biologic therapy was similar across all regions. DAS28 scores were well recorded within patient records at baseline and 6 months but not at other time points. CONCLUSIONS: Our data highlight that nearly a quarter of patients receiving biologic treatments are not receiving concomitant sDMARD therapy and that DAS28 is poorly documented in patient medical records other than when initiating biologics and at the 6-month review. Limitations of this study include the limited sample size, the retrospective rather than prospective nature of the audit and the use of medical records only rather than other records such as nursing and pharmacy data. Nevertheless, the reasons for our findings merit further investigation to ensure that optimum treatment regimes and long term outcomes are being achieved for patients.

Background Public Health England (PHE) estimates that there are upwards of 160,000 individuals in England and Wales with chronic hepatitis C virus (HCV) infection, but until now only around 100,000 laboratory diagnoses have been reported to PHE and of these 28,000 have been treated. Targeted case-finding in primary care is estimated to be cost-effective; however, there has been no robust randomised controlled trial evidence available of specific interventions. Therefore, this study aims to develop and conduct a complex intervention within primary care and to evaluate this approach using a cluster randomised controlled trial. Methods/design A total of 46 general practices in South West England will be randomised in a 1:1 ratio to receive either a complex intervention comprising: educational training on HCV for the practice; poster and leaflet display in the practice waiting rooms to raise awareness and encourage opportunistic testing; a HCV risk prediction algorithm based on information on possible risk markers in the electronic patient record run using Audit + software (BMJ Informatica). The audit will then be used to recall and offer patients a HCV test. Control practices will follow usual care. The effectiveness of the intervention will be measured by comparing number and rates of HCV testing, the number and proportion of patients testing positive, onward referral, rates of specialist assessment and treatment in control and intervention practices. Intervention costs and health service utilisation will be recorded to estimate the NHS cost per new HCV diagnosis and new HCV patient initiating treatment. Longer-term cost-effectiveness of the intervention in improving quality-adjusted life years (QALYs) will be extrapolated using a pre-existing dynamic health economic model. Patients’ and health care workers’ experiences and acceptability of the intervention will be explored through semi-structured qualitative interviews. Discussion This trial has the potential to make an important impact on patient care and will provide high-quality evidence to help general practitioners make important decisions on HCV testing and onward referral. If found to be effective and cost-effective the intervention is readily scalable and can be used to support the implementation of NICE recommendations on HCV case-finding. Trial registration ISRCTN61788850. Registered on 24 April 2015; Protocol Version: 2.0, 22 May 2015. Electronic supplementary material The online version of this article (doi:10.1186/s13063-016-1501-3) contains supplementary material, which is available to authorized users.

A relationship between dopamine and temperament has previously been described in human cases of dopaminergic dysfunction. Adjustment in temperament prior to disease manifestation can enable the early identification of individuals at risk of such conditions, and scope exists to extend this application of temperament alterations to cases of dopaminergic dysfunction in horses. A multivariate and mixed-methods approach utilising a questionnaire along with two inferred measurements of dopamine activity (Spontaneous Blink Rate [SBR] and Behavioral Initiation Rate [BIR]) were recorded from direct observation of animals (n = 99) to identify the potential relationship between dopamine and temperament in horses. Principal components analysis (PCA) of 36 temperament variables revealed nine Principal Components, including ‘Anxiety’ and ‘Docility’, which accounted for 72.4% of the total variance. Component scores were calculated and correlated with SBR and BIR utilising Spearman Rank Correlation Coefficient analysis. The component ‘Anxiety’ was found to have a significant positive relationship with SBR, whereas ‘Docility’ was observed to have a significant negative relationship with SBR. These results indicate a relationship between dopamine and temperament within the horse that is certainly worthy of further study. Potential mechanisms involving neural dopaminergic and GABAergic systems are presented, in addition to how such alterations could be utilised to probe for equine dopamine dysfunction pending future research.

Background In order to improve lung cancer survival in the UK, a greater proportion of resectable cancers must be diagnosed. It is likely that resectability rates would be increased by more timely diagnosis. Aside from screening, the only way of achieving this is to reduce the time to diagnosis in symptomatic cancers. Currently, lung cancers are mainly diagnosed by general practitioners (GPs) using the National Institute for Health and Clinical Excellence (NICE) guidelines for urgent referral for chest X-ray, which recommend urgent imaging or referral for patients who have one of a number of chest symptoms for more than 3 weeks. We are proposing to expand this recommendation to include one of a number of chest symptoms of any duration in higher-risk patients. Methods/Design We intend to conduct a trial of imaging in these higher-risk patients and compare it with NICE guidelines to see if imaging improves stage at diagnosis and resection rates. This trial would have to be large (and consequently resource-intensive) because most of these patients will not have lung cancer, making optimal design crucial. We are therefore conducting a pilot trial that will ascertain the feasibility of running a full trial and provide key information that will be required in order to design the full trial. Discussion This trial will assess the feasibility and inform the design of a large, UK-wide, clinical trial of a change to the NICE guidelines for urgent referral for chest X-ray for suspected lung cancer. It utilizes a combination of workshop, health economic, quality of life, qualitative, and quantitative methods in order to fully assess feasibility. Trial registration Clinicaltrials.gov NCT01344005

This phenomenological study examined relatives' lived experiences of complementary therapies in the Department of Critical Care Medicine at Royal Hobart Hospital. Participants in the study, 20 relatives of critically ill patients, were involved in a non-structured, audiotaped interview. Subsequently, transcripts were analysed using a phenomenological transformative process to identify common themes in the text. Study findings suggested four emerging conceptual categories, which with further analysis uncovered the essence of the phenomenon as extending and enriching a caring atmosphere.

Background\ud The ELCID Trial is a feasibility randomised controlled\ud trial examining the effect on lung cancer diagnosis of\ud giving an urgent chest x-ray to smokers, and recent exsmokers,\ud aged over 60 with new chest symptoms.\ud Aims\ud The qualitative component explores the feasibility of\ud individually randomising patients to an urgent CXR or\ud not and investigates any barriers to patient participation.\ud Methods\ud To date we have conducted semi-structured interviews\ud with six primary care staff (practice managers, research\ud nurses), ten patients randomised to ‘extra-NICE’ guidelines\ud for referral for urgent chest x-ray, and six patients\ud randomised to ‘usual care’ (NICE guidelines)). We hope\ud to also interview patients who decline randomisation.\ud Interviews were analysed using a Framework approach.\ud Results\ud Initial analysis indicated that practices have struggled to\ud recruit patients, partly due to the eligibility criteria that\ud requires ex-smokers to have stopped smoking within the\ud last five years. Practices with a research nurse have\ud recruited the most patients. Patients indicated that they\ud are happy to take part in the trial and their anxiety\ud levels were not raised. Most patients hoped to be\ud randomised to urgent chest x-ray, although those who\ud were not did not go back to their GP to request one.\ud Conclusions\ud Eligibility criteria needed revision to include ex-smokers\ud of any duration. These preliminary findings suggest that\ud the trial appears to be feasible and patients are happy to\ud accept randomisation. The findings will inform the\ud design of the main trial in the future.