Methylphenidate Versus Placebo for Treating Fatigue in Patients With Advanced Cancer: Randomized, Double-Blind, Multicenter, Placebo-Controlled Trial.

PURPOSE: To compare effects and side effects of 6 weeks of individually dose-titrated methylphenidate or placebo on fatigue in palliative care patients with advanced cancer. METHODS: This is a randomized, double-blind, placebo-controlled, multicenter trial. Eligible patients had advanced incurable cancer and fatigue >3/10. Principal exclusions were hypertension; psychiatric, cardiovascular, cerebrovascular, renal, liver, or blood disorders; substance dependency; and epilepsy. Patients were randomly assigned 1:1 methylphenidate or placebo starting at 5 mg twice daily. Dose of methylphenidate/placebo was titrated once per week, over 6 weeks, up to a maximum of 20 mg three times daily. Trial ended at 10 weeks. Primary outcome was the difference in Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) scores between groups at 6 ± 2 weeks. Secondary outcomes included adverse effects, quality of life, and mood. RESULTS: One hundred sixty-two patients (73 men; mean, 65.8; standard deviation [SD], 10.3 years) were randomly assigned, and three were excluded from analysis. Seventy-seven were allocated placebo (baseline FACIT-F = 22 [SD, 10]); 82 were allocated methylphenidate (FACIT-F = 20 [SD, 9]). After 6 ± 2 weeks, FACIT-F scores were 1.97 points (95% CI, -0.95 to 4.90; P = .186) higher (better) on methylphenidate than placebo. Across 10 weeks of the study, FACIT-F was nominally higher in the methylphenidate group versus placebo (Diff, 2.20 [95% CI, 0.39 to 4.01]), but this did not reach the minimally clinically important difference (5-points). At 6 weeks, there were no differences between groups in quality-of-life or symptom domains except for depression scores (nominally reduced in the methylphenidate group: Diff, -1.35 [95% CI, -2.41 to -0.30]). There were no differences in mortality or serious adverse events. CONCLUSION: After 6 ± 2 weeks of treatment, methylphenidate was not superior to placebo for treating fatigue in advanced cancer. Methylphenidate was safe and well-tolerated.

A randomised phase II trial of temozolomide with or without cannabinoids in patients with recurrent glioblastoma (ARISTOCRAT): protocol for a multi-centre, double-blind, placebo-controlled trial.

BACKGROUND: Glioblastoma (GBM) is the most common adult malignant brain tumour, with an incidence of 5 per 100,000 per year in England. Patients with tumours showing O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation represent around 40% of newly diagnosed GBM. Relapse/tumour recurrence is inevitable. There is no agreed standard treatment for patients with GBM, therefore, it is aimed at delaying further tumour progression and maintaining health-related quality of life (HRQoL). Limited clinical trial data exist using cannabinoids in combination with temozolomide (TMZ) in this setting, but early phase data demonstrate prolonged overall survival compared to TMZ alone, with few additional side effects. Jazz Pharmaceuticals (previously GW Pharma Ltd.) have developed nabiximols (trade name Sativex®), an oromucosal spray containing a blend of cannabis plant extracts, that we aim to assess for preliminary efficacy in patients with recurrent GBM. METHODS: ARISTOCRAT is a phase II, multi-centre, double-blind, placebo-controlled, randomised trial to assess cannabinoids in patients with recurrent MGMT methylated GBM who are suitable for treatment with TMZ. Patients who have relapsed ≥ 3 months after completion of initial first-line treatment will be randomised 2:1 to receive either nabiximols or placebo in combination with TMZ. The primary outcome is overall survival time defined as the time in whole days from the date of randomisation to the date of death from any cause. Secondary outcomes include overall survival at 12 months, progression-free survival time, HRQoL (using patient reported outcomes from QLQ-C30, QLQ-BN20 and EQ-5D-5L questionnaires), and adverse events. DISCUSSION: Patients with recurrent MGMT promoter methylated GBM represent a relatively good prognosis sub-group of patients with GBM. However, their median survival remains poor and, therefore, more effective treatments are needed. The phase II design of this trial was chosen, rather than phase III, due to the lack of data currently available on cannabinoid efficacy in this setting. A randomised, double-blind, placebo-controlled trial will ensure an unbiased robust evaluation of the treatment and will allow potential expansion of recruitment into a phase III trial should the emerging phase II results warrant this development. TRIAL REGISTRATION: ISRCTN: 11460478. CLINICALTRIALS: Gov: NCT05629702.

Understanding how shared decision-making approaches and patient aids influence patients with advanced cancer when deciding on palliative treatments and care: A realist review.

BACKGROUND: Patients with advanced incurable cancer face difficult decisions about palliative treatment options towards their end of life. However, they are often not provided with the appropriate information and support that is needed to make informed decisions. This review aimed to identify contexts and mechanisms associated with communication tools, patient decision-aids and shared decision-making (SDM) approaches that influence patient outcomes. METHODS: We used a realist review method to search for published studies of patients (adults > 18) with advanced cancer who were expected to make a decision about palliative treatment and/or supportive care in consultation with healthcare practitioners. We appraised and synthesised literature describing the contexts of (when and how) decision aids and SDM approaches are used, and how these contexts interact with mechanisms (resources and reasoning) which impact patient outcomes. Stakeholders including academics, palliative healthcare professionals (HCPs) and people with lived experience of supporting people with advanced incurable cancer contributed to identifying explanatory accounts. These accounts were documented, analysed and consolidated to contribute to the development of a programme theory. RESULTS: From the 33 included papers, we consolidated findings into 20 explanatory accounts to develop a programme theory that explains key contexts and mechanisms that influence patient and SDM. Contexts include underlying patients' and HCPs' attitudes and approaches. These need to be understood in relation to key mechanisms, including presenting information in multiple formats and providing adequate time and opportunities to prepare for and revisit decisions. Contexts influenced mechanisms which then influence the levels of patient decisional satisfaction, conflict and regret. CONCLUSIONS: Our programme theory highlights mechanisms that are important in supporting shared treatment decisions for advanced noncurative cancer. The findings are informative for developing and evaluating interventions to improve understanding and involvement in SDM for patients with advanced incurable cancer. PATIENT AND PUBLIC CONTRIBUTION: We included patient and public involvement (PPI) representatives in four stakeholder meetings. PPI helped to define the scope of the review, identify their unique experiences and perspectives, synthesise their perspectives with our review findings, make decisions about which theories we included in our programme theory and develop recommendations for policy and practice and future research.

Pathway map development for medical device event reporting in operating theatres: a human factors approach to improving the existing system.

Objectives: This study aimed to develop the actual pathway to reporting and information transfer in operating theatres in relation to medical technology malfunction/failure. This with the aim of understanding the differences with the pathway published by NHS Improvement and identification of points for improvement. Design: This is a qualitative study involving stakeholder interviews with doctors, nurses, manufacturers, medical device safety officer and Medicines and Healthcare products Regulatory Agency. Setting: Data were collected on reporting pathway used in operating theatres. Clinical staff who took part worked in different trusts throughout UK while manufacturers provided devices in UK and EU/USA. Participants: Semistructured interviews were completed with 15 clinicians and 13 manufacturers. Surveys were completed by 38 clinicians and 5 manufacturers. Recognised methods of pathway development were used. The Lean Six Sigma principles adapted to healthcare were used to develop suggestions for improvement. Main outcome measures: To identify the differences between the set pathway to reporting and information transfer to what is occurring on a day-to-day basis as reported by staff. Identify points in the pathway where improvements could be applied. Results: The developed pathway demonstrated great complexity of the current reporting system for medical devices. It identified numerous areas that give rise to problems and multiple biases in decision making. This highlighted the core issues leading to under-reporting and lack of knowledge on device performance and patient risk. Suggestions for improvement were deduced based on end user requirements and identified problems. Conclusions: This study has provided a detailed understanding of the key problem areas that exist within the current reporting system for medical devices and technology. The developed pathway sets to address the key problems to improve reporting outcomes. The identification of pathway differences between 'work as done' and 'work as imagined' can lead to development of quality improvements that could be systematically applied.

Communication of palliative care needs in discharge letters from hospice providers to primary care: a multisite sequential explanatory mixed methods study.

BACKGROUND: The provision of palliative care is increasing, with many people dying in community-based settings. It is essential that communication is effective if and when patients transition from hospice to community palliative care. Past research has indicated that communication issues are prevalent during hospital discharges, but little is known about hospice discharges. METHODS: An explanatory sequential mixed methods study consisting of a retrospective review of hospice discharge letters, followed by hospice focus groups, to explore patterns in communication of palliative care needs of discharged patients and describe why these patients were being discharged. Discharge letters were extracted for key content information using a standardised form. Letters were then examined for language patterns using a linguistic methodology termed corpus linguistics. Thematic analysis was used to analyse the focus group transcripts. Findings were triangulated to develop an explanatory understanding of discharge communication from hospice care. RESULTS: We sampled 250 discharge letters from five UK hospices whereby patients had been discharged to primary care. Twenty-five staff took part in focus groups. The main reasons for discharge extracted from the letters were symptoms "managed/resolved" (75.2%), and/or the "patient wishes to die/for care at home" (37.2%). Most patients had some form of physical needs documented on the letters (98.4%) but spiritual needs were rarely documented (2.4%). Psychological/emotional needs and social needs were documented in 46.4 and 35.6% of letters respectively. There was sometimes ambiguity in "who" will be following up "what" in the discharge letters, and whether described patients' needs were resolved or ongoing for managing in the community setting. The extent to which patients received a copy of their discharge letter varied. Focus groups conveyed a lack of consensus on what constitutes "complexity" and "complex pain". CONCLUSIONS: The content and structure of discharge letters varied between hospices, although generally focused on physical needs. Our study provides insights into patterns associated with those discharged from hospice, and how policy and guidance in this area may be improved, such as greater consistency of sharing letters with patients. A patient-centred set of hospice-specific discharge letter principles could help improve future practice.

Current status of medical device malfunction reporting: using end user experience to identify current problems.

INTRODUCTION: The current under-reporting of medical device malfunctions, difficulties with the current system and absence of continuous good-quality data has removed the possibility for constant data interrogation and trend recognition to identify evolving issues. This research used end user experiences aiming to understand causes for the lack of data and knowledge on device performance and associated patient risks. This approach was used to identify existing barriers and methods for improvement. METHODS: This is a qualitative study involving semistructured interviews and surveys with clinicians (15 interviews, 39 surveys) and manufacturers (13 interview participants, 5 surveys). Multiple sources of recruiting were used. Data collected were thematically analysed. Interview results were used to design the surveys. Standards for Reporting Qualitative Research was used. RESULTS: Medical device use is based on personal experience rather than evidence which is scarce. Multiple barriers to reporting were identified alongside patient safety and system related aspects. Furthermore, the acceptable level of error was variable as were effects on working practice. Many workarounds have been developed to overcome problems and have become normalised in daily work. These factors were found to have a limiting impact on improvements and learning. Greater system transparency, feedback on submitted reports, a more efficient system of reporting and better communication with manufacturers were reported as some of the required improvements. CONCLUSIONS: This study has identified numerous complex issues affecting reporting of medical device performance and their subsequent effect on patient safety and clinical staff. The focus on incidents has created many limitations to learning and development. The rich experience of end users should be appropriately used to identify system weaknesses and seek improvement methods. Better communication methods should be developed between healthcare and MedTech (Medical Technologies) industry.

Development and validation of ester impregnated pH strips for locating nasogastric feeding tubes in the stomach-a multicentre prospective diagnostic performance study.

BACKGROUND: NG (nasogastric) tubes are used worldwide as a means to provide enteral nutrition. Testing the pH of tube aspirates prior to feeding is commonly used to verify tube location before feeding or medication. A pH at or lower than 5.5 was taken as evidence for stomach intubation. However, the existing standard pH strips lack sensitivity, especially in patients receiving feeding and antacids medication. We developed and validated a first-generation ester-impregnated pH strip test to improve the accuracy towards gastric placements in adult population receiving routine NG-tube feeding. The sensitivity was improved by its augmentation with the action of human gastric lipase (HGL), an enzyme specific to the stomach. METHODS: We carried out a multi-centred, prospective, two-gate diagnostic accuracy study on patients who require routine NG-tube feeding in 10 NHS hospitals comparing the sensitivity of the novel pH strip to the standard pH test, using either chest X-rays or, in its absence, clinical observation of the absence of adverse events as the reference standard. We also tested the novel pH strips in lung aspirates from patients undergoing oesophageal cancer surgeries using visual inspection as the reference standard. We simulated health economics using a decision analytic model and carried out adoption studies to understand its route to commercialisation. The primary end point is the sensitivity of novel and standard pH tests at the recommended pH cut-off of 5.5. RESULTS: A total of 6400 ester-impregnated pH strips were prepared based on an ISO13485 quality management system. A total of 376 gastric samples were collected from adult patients in 10 NHS hospitals who were receiving routine NG-tube feeding. The sensitivities of the standard and novel pH tests were respectively 49.2% (95% CI 44.1­54.3%) and 70.2% (95% CI 65.6­74.8%) under pH cut-off of 5.5 and the novel test has a lung specificity of 89.5% (95% CI 79.6%, 99.4%). Our simulation showed that using the novel test can potentially save 132 unnecessary chest X-rays per check per every 1000 eligible patients, or direct savings of £4034 to the NHS. CONCLUSIONS: The novel pH test correctly identified significantly more patients with tubes located inside the stomach compared to the standard pH test used widely by the NHS. TRIAL REGISTRATION: http://www.isrctn.com/ISRCTN11170249 , Registered 21 June 2017-retrospectively registered.

Randomised controlled trial and economic evaluation of a targeted cancer awareness intervention for adults living in deprived areas of the UK.

BACKGROUND: Cancer outcomes are poor in socioeconomically deprived communities, with low symptom awareness contributing to prolonged help-seeking and advanced disease. Targeted cancer awareness interventions require evaluation. METHODS: This is a randomised controlled trial involving adults aged 40+ years recruited in community and healthcare settings in deprived areas of South Yorkshire and South-East Wales. INTERVENTION: personalised behavioural advice facilitated by a trained lay advisor. CONTROL: usual care. Follow-up at two weeks and six months post-randomisation. PRIMARY OUTCOME: total cancer symptom recognition score two weeks post-randomisation. RESULTS: Two hundred and thirty-four participants were randomised. The difference in total symptom recognition at two weeks [adjusted mean difference (AMD) 0.6, 95% CI: -0.03, 1.17, p = 0.06] was not statistically significant. Intervention participants reported increased symptom recognition (AMD 0.8, 95% CI: 0.18, 1.37, p = 0.01) and earlier intended presentation (AMD -2.0, 95% CI: -3.02, -0.91, p < 0.001) at six months. "Lesser known" symptom recognition was higher in the intervention arm (2 weeks AMD 0.5, 95% CI: 0.03, 0.97 and six months AMD 0.7, 95% CI: 0.16, 1.17). Implementation cost per participant was £91.34, with no significant between-group differences in healthcare resource use post-intervention. CONCLUSIONS: Improved symptom recognition and earlier anticipated presentation occurred at longer-term follow-up. The ABACus Health Check is a viable low-cost intervention to increase cancer awareness in socioeconomically deprived communities. CLINICAL TRIAL REGISTRATION: ISRCTN16872545.

Attitudes towards Trusting Artificial Intelligence Insights and Factors to Prevent the Passive Adherence of GPs: A Pilot Study.

Artificial Intelligence (AI) systems could improve system efficiency by supporting clinicians in making appropriate referrals. However, they are imperfect by nature and misdiagnoses, if not correctly identified, can have consequences for patient care. In this paper, findings from an online survey are presented to understand the aptitude of GPs (n = 50) in appropriately trusting or not trusting the output of a fictitious AI-based decision support tool when assessing skin lesions, and to identify which individual characteristics could make GPs less prone to adhere to erroneous diagnostics results. The findings suggest that, when the AI was correct, the GPs' ability to correctly diagnose a skin lesion significantly improved after receiving correct AI information, from 73.6% to 86.8% (X2 (1, N = 50) = 21.787, p < 0.001), with significant effects for both the benign (X2 (1, N = 50) = 21, p < 0.001) and malignant cases (X2 (1, N = 50) = 4.654, p = 0.031). However, when the AI provided erroneous information, only 10% of the GPs were able to correctly disagree with the indication of the AI in terms of diagnosis (d-AIW M: 0.12, SD: 0.37), and only 14% of participants were able to correctly decide the management plan despite the AI insights (d-AIW M:0.12, SD: 0.32). The analysis of the difference between groups in terms of individual characteristics suggested that GPs with domain knowledge in dermatology were better at rejecting the wrong insights from AI.

Prognostic models of survival in patients with advanced incurable cancer: the PiPS2 observational study.

BACKGROUND: The Prognosis in Palliative care Study (PiPS) prognostic survival models predict survival in patients with incurable cancer. PiPS-A (Prognosis in Palliative care Study - All), which involved clinical observations only, and PiPS-B (Prognosis in Palliative care Study - Blood), which additionally required blood test results, consist of 14- and 56-day models that combine to create survival risk categories: 'days', 'weeks' and 'months+'. OBJECTIVES: The primary objectives were to compare PIPS-B risk categories against agreed multiprofessional estimates of survival and to validate PiPS-A and PiPS-B. The secondary objectives were to validate other prognostic models, to assess the acceptability of the models to patients, carers and health-care professionals and to identify barriers to and facilitators of clinical use. DESIGN: This was a national, multicentre, prospective, observational, cohort study with a nested qualitative substudy using interviews with patients, carers and health-care professionals. SETTING: Community, hospital and hospice palliative care services across England and Wales. PARTICIPANTS: For the validation study, the participants were adults with incurable cancer, with or without capacity to consent, who had been recently referred to palliative care services and had sufficient English language. For the qualitative substudy, a subset of participants in the validation study took part, along with informal carers, patients who declined to participate in the main study and health-care professionals. MAIN OUTCOME MEASURES: For the validation study, the primary outcomes were survival, clinical prediction of survival and PiPS-B risk category predictions. The secondary outcomes were predictions of PiPS-A and other prognostic models. For the qualitative substudy, the main outcomes were participants' views about prognostication and the use of prognostic models. RESULTS: For the validation study, 1833 participants were recruited. PiPS-B risk categories were as accurate as agreed multiprofessional estimates of survival (61%; p = 0.851). Discrimination of the PiPS-B 14-day model (c-statistic 0.837, 95% confidence interval 0.810 to 0.863) and the PiPS-B 56-day model (c-statistic 0.810, 95% confidence interval 0.788 to 0.832) was excellent. The PiPS-B 14-day model showed some overfitting (calibration in the large -0.202, 95% confidence interval -0.364 to -0.039; calibration slope 0.840, 95% confidence interval 0.730 to 0.950). The PiPS-B 56-day model was well-calibrated (calibration in the large 0.152, 95% confidence interval 0.030 to 0.273; calibration slope 0.914, 95% confidence interval 0.808 to 1.02). PiPS-A risk categories were less accurate than agreed multiprofessional estimates of survival (p < 0.001). The PiPS-A 14-day model (c-statistic 0.825, 95% confidence interval 0.803 to 0.848; calibration in the large -0.037, 95% confidence interval -0.168 to 0.095; calibration slope 0.981, 95% confidence interval 0.872 to 1.09) and the PiPS-A 56-day model (c-statistic 0.776, 95% confidence interval 0.755 to 0.797; calibration in the large 0.109, 95% confidence interval 0.002 to 0.215; calibration slope 0.946, 95% confidence interval 0.842 to 1.05) had excellent or reasonably good discrimination and calibration. Other prognostic models were also validated. Where comparisons were possible, the other prognostic models performed less well than PiPS-B. For the qualitative substudy, 32 health-care professionals, 29 patients and 20 carers were interviewed. The majority of patients and carers expressed a desire for prognostic information and said that PiPS could be helpful. Health-care professionals said that PiPS was user friendly and may be helpful for decision-making and care-planning. The need for a blood test for PiPS-B was considered a limitation. LIMITATIONS: The results may not be generalisable to other populations. CONCLUSIONS: PiPS-B risk categories are as accurate as agreed multiprofessional estimates of survival. PiPS-A categories are less accurate. Patients, carers and health-care professionals regard PiPS as potentially helpful in clinical practice. FUTURE WORK: A study to evaluate the impact of introducing PiPS into routine clinical practice is needed. TRIAL REGISTRATION: Current Controlled Trials ISRCTN13688211. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 28. See the NIHR Journals Library website for further project information.

A prognosis is a prediction about how long someone will live after a diagnosis of illness. The Prognosis in Palliative care Study (PiPS) tools [PiPS-A (Prognosis in Palliative care Study ­ All) and PiPS-B (Prognosis in Palliative care Study ­ Blood), respectively] were designed to predict survival in patients with incurable cancer. Previously, they were found to be as accurate as health-care professionals. The purpose of this study was to find out whether PiPS was more accurate at prognosticating than health-care professionals, to evaluate other prognostic tools and to ask patients, their carers and health-care professionals what they thought about using them. We studied 1833 patients with advanced cancer and calculated their PiPS score and other prognostic scores. We asked health-care professionals to estimate how long the patients would live. We then followed up the patients to find out how long they actually lived and if the predictions made by health-care professionals were as accurate as the predictions made by the prognostic tools. We interviewed patients, their carers and health-care professionals to ask them what they thought about using these prognostic tools. We found that PiPS-B was as accurate as the combined wisdom of a doctor and a nurse at predicting whether patients would live for 'days', 'weeks' or 'months+'. We found that PiPS-A predictions were not as accurate as predictions made by health-care professionals. We found that (where direct comparisons could be made) PiPS-B was better than other prognostic tools. Finally, we found that patients, carers and health-care professionals thought that PiPS tools could be helpful in clinical practice because they would be less subjective than clinicians' intuition. This means that PiPS-B could be considered as a tool to support clinician predictions of survival and may lead to patients and families being able to take more control at the end of their lives. Further research will be required to investigate whether or not this approach actually leads to improvements in care.

Recruitment and retention of participants from socioeconomically deprived communities: lessons from the Awareness and Beliefs About Cancer (ABACus3) Randomised Controlled Trial.

BACKGROUND: Recruitment of research participants poses challenges in socioeconomically deprived areas. The Awareness and Beliefs About Cancer (ABACus) phase 3 Randomised Control Trial recruited adult participants from socioeconomically deprived areas using a combined healthcare/community engagement model. We report the strategies used to successfully recruit and retain our trial participant sample. METHODS: Community and healthcare settings in areas of high socioeconomic deprivation were identified by lay advisors who recruited participants opportunistically or by appointment. Follow-up was done by telephone or post at 2-weeks and 6-months after recruitment, and all participants were offered financial incentives. Qualitative interviews were conducted with lay advisors regarding their experience and reflections. RESULTS: The lay advisors identified and contacted 107 potential recruitment venues across South and West Yorkshire and South East Wales of which 41.1% (n = 42) were opened for recruitment. A total of 234 participants were recruited, with 91% (n = 212) retention at 2-weeks and 85% (n = 199) at 6-months. Community settings yielded 75% (n = 176) of participants. Participants had a mean age of 61.3 years and 63.3% (n = 148) were female, with 66% (n = 154) resident in the most deprived geographical areas. Lay advisors described recruitment as intensive, although engaging participants was easier in community settings. CONCLUSIONS: The ABACus3 trial achieved recruitment and high retention with a population that is often "hard to reach" or entirely missed in health research. Strategies were specifically tailored to engage the venues and adult residents of highly deprived areas. Future studies recruiting adults living in the most deprived areas might benefit from community recruitment and from collaborating with local gatekeepers who are key to engagement. This study adheres to CONSORT guidelines. TRIAL REGISTRATION: Retrospectively registered with ISRCTN ( http://www.isrctn.com/ISRCTN16872545 ) on 12.01.2018.

Improving cancer symptom awareness and help-seeking among adults living in socioeconomically deprived communities in the UK using a facilitated health check: A protocol for the Awareness and Beliefs About Cancer (ABACus) Randomised Control Trial.

BACKGROUND: Cancer survival is lower in socioeconomically deprived communities, partly due to low awareness of symptoms, negative beliefs and delayed help-seeking. We developed an interactive health check questionnaire facilitated by trained lay advisors. It entails 29 questions about background, lifestyle and health with tailored behaviour change advice. Personalised results are printed using a traffic light (red/amber/green) system, highlighting areas where action should be taken. This is an individually randomised control trial to test effectiveness of the health check on symptom recognition. METHODS: A total 246 participants aged 40+ years will be recruited from community and healthcare settings in socioeconomically deprived areas of Yorkshire and South Wales. Participants will be randomised to receive the health check or standard care (1:1 ratio). Outcome measures include: adapted Awareness and Beliefs about Cancer (primary outcome), brief State Trait Anxiety Inventory, intentions and motivation to adopt recommended health behaviours (early symptom presentation, cancer screening and lifestyle behaviours), adapted Client Service Receipt Inventory, brief medical history/screening and demographic questionnaire at: baseline; 2-weeks; and 6-months post-randomisation. A purposive sample of intervention sessions will be audio-recorded (n = 24) and half will additionally be observed (n = 12). Semi-structured interviews will take place at 2-weeks (n = 30) and 6-months (n = 15-20) post-randomisation. The primary analysis will compare cancer symptom recognition scores between arms at 2-weeks. Secondary analysis will assess cancer beliefs, barriers/time to presentation, screening and lifestyle behaviours, anxiety and costs. A process evaluation will assess intervention fidelity, dose and contamination. The London-Surrey NHS Research Ethics Committee (Ref: 17/LO/1507) approved this trial. DISCUSSION: This is a trial of a theoretically underpinned complex intervention which has undergone phase 1 and 2 development work. The findings will evaluate evidence about the effect of the health check on symptom awareness. Although there are few exclusion criteria there are limitations regarding the population we are able to reach, who may have even higher risks of late diagnosis and poor cancer prognosis. However, the health check has the potential to improve cancer symptom awareness and encourage early help-seeking behaviour in deprived populations, thereby reducing inequalities in longer term cancer outcomes. TRIAL REGISTRATION: Retrospectively registered with ISRCTN (Ref: ISRCTN16872545 ) on 12.01.2018.

State of science: human factors and ergonomics in healthcare.

The past decade has seen an increase in the application of human factors and ergonomics (HFE) techniques to healthcare delivery in a broad range of contexts (domains, locations and environments). This paper provides a state of science commentary using four examples of HFE in healthcare to review and discuss analytical and implementation challenges and to identify future issues for HFE. The examples include two domain areas (occupational ergonomics and surgical safety) to illustrate a traditional application of HFE and the area that has probably received the most research attention. The other two examples show how systems and design have been addressed in healthcare with theoretical approaches for organisational and socio-technical systems and design for patient safety. Future opportunities are identified to develop and embed HFE systems thinking in healthcare including new theoretical models and long-term collaborative partnerships. HFE can contribute to systems and design initiatives for both patients and clinicians to improve everyday performance and safety, and help to reduce and control spiralling healthcare costs. PRACTITIONER SUMMARY: There has been an increase in the application of HFE techniques to healthcare delivery in the past 10 years. This paper provides a state of science commentary using four illustrative examples (occupational ergonomics, design for patient safety, surgical safety and organisational and socio-technical systems) to review and discuss analytical and implementation challenges and identify future issues for HFE.

Ergonomic risk assessment of nasogastric tube placement and implications for design and training.

The placement of nasogastric (NG) tubes is known to be prone to error and may lead to serious issues for patient safety and wellbeing. In some instances these have been catastrophic and resulted in the death of the patient. This study sought to explore the potential risks associated with this procedure through the use of systematic prospective risk assessment. The research team used the Prospective Hazard Analysis (PHA) toolkit developed by Ward et al (2010) . The study has shown a wide number of risks that cover equipment design, work organisation, and training issues. The link between equipment design and training provides an important example of the need for a systematic approach to reducing errors and improving resilience in this aspect of healthcare.

Designing packaging to support the safe use of medicines at home.

In the light of a number of serious incidents in the UK resulting from accidental overdoses of methotrexate, this study investigated how the design of methotrexate packaging can influence patient safety, and aimed to collect evidence to provide a basis for the development of new concepts for revised designs by the pharmaceutical industry. The research found that patients using methotrexate experience a number of difficulties in using their medicines packaging, and as a result, resourcefully adopt a variety of "coping strategies" which may increase the risk of dosing errors. By investigating both the practice of methotrexate users, and the design of the system that supports methotrexate use, additional problems were observed across the healthcare system, meaning that the function of medicines packaging in ensuring safety may be even more critical than first suspected. As a result of this research the National Patient Safety Agency responded with a UK-wide programme of work to improve safety for patients, and continues to work with the pharmaceutical industry to develop more user-friendly packaging and labelling.