Evidence suggests a 38% risk reduction in breast and bowel cancer-specific mortality with higher levels of exercise, however, most of this evidence is observational. More clinical trials are needed to build strong evidence for exercise’s impact on recurrence and survival. This study aims to assess the feasibility, acceptability and potential efficacy of a remote, tailored exercise programme on disease-free survival in patients recently completing curative treatment for early-stage, high-risk lung, breast or bowel cancer.
This UK-based, multicentre randomised controlled basket feasibility trial compares a personalised, remote-delivered exercise programme supported by exercise professionals against usual care. Potential participants are approached if they are: aged 18 or over, diagnosed with high-risk, early-stage breast, bowel or lung cancer, and within 24 weeks of completing primary curative treatments. Participants complete objective measures of physical function (submaximal cardiovascular fitness, endurance, muscle strength and balance), body composition (bioelectrical impedance) and self-reported outcomes (total physical activity, sleep quality, general quality of life (QoL), cancer-related QoL and exercise confidence/motivation). Clinical case note review provides disease-free survival outcomes at 6, 12 and 24 months. The 12-week programme is delivered remotely (via phone, email and/or video conference) with trainer contact tapering off over the subsequent 12 weeks (24 weeks total). Recruitment is ongoing with a 660-participant goal. Descriptive measures (quantitative and qualitative) will be reported for feasibility outcomes: recruitment, adherence, retention rates, data collection quality, adverse events, intervention acceptability and fidelity. A process evaluation is being conducted concurrently and is reported separately. Kaplan-Meier curves will be plotted and median disease-free survival calculated for each arm. To determine intervention impact, a log-rank test (unadjusted) will compare 2-year disease-free survival between groups within and among cancer types. Secondary outcomes (physical function status, general/cancer-specific QoL and determinants of meeting activity guidelines) will be reported at each time point.
Ethical approvals were obtained through Hull York Medical School (ID: 23/SS/0060) and UK NHS Health Research Authority (ID: 327663). Findings will be submitted for publication in high-impact journals, presentation at national and international conferences, press releases where appropriate, and dissemination activities to be decided on with the Patient Advisory Group.
The UK’s medical workforce is under increasing strain, and this is compounded by increasing numbers of resident doctors diverging from specialist training pathways, instead entering non-training roles, reducing clinical hours or leaving the profession or UK workforce entirely. These decisions are shaped by both individual motivations and wider structural conditions, including unsatisfactory working conditions, limited flexibility and a perceived lack of support or autonomy. While pursuing alternative career routes offers personal and professional benefits, they can also delay progression to senior clinical roles, contributing to workforce instability. There remains limited understanding of how best to support retention, particularly given the varied contexts, settings and career trajectories of resident doctors. This realist synthesis will examine how, why and in what contexts resident doctors leave the National Health Service, and what interventions might support their retention.
This realist synthesis will follow Realist And Meta-narrative Evidence Synthesis: Evolving Standards guidance and will be conducted in five iterative steps: (1) identifying existing theories to develop an initial programme theory; (2) undertaking formal and purposive searches to identify relevant UK-based literature; (3) selecting documents based on relevance and rigour; (4) extracting and coding data to support the development of explanatory insights; and (5) synthesising findings using a realist logic of analysis to develop and refine context-mechanism-outcome configurations. An advisory group will guide the review throughout. The final programme theory will inform the development of evidence-based recommendations and design principles to support resident doctor retention.
Ethical approval is not required for this synthesis of existing literature. Findings will be disseminated through academic publications, conference presentations and accessible formats, including infographics, plain English summaries and blog posts. Target audiences include resident doctors, medical educators, workforce planners and policymakers.
PROSPERO, CRD420251004453.
Scoping reviews, mapping reviews and evidence and gap maps (collectively known as ‘big picture reviews’) in health continue to gain popularity within the evidence ecosystem. These big-picture reviews are beneficial for policy-makers, guideline developers and researchers within the field of health for understanding the available evidence, characteristics, concepts and research gaps, which are often needed to support the development of policies, guidelines and practice. However, these reviews often face criticism related to poor and inconsistent methodological conduct and reporting. There is a need to understand which areas of these reviews require further methodological clarification and exploration. The aim of this project is to develop a research agenda for scoping reviews, mapping reviews and evidence and gap maps in health by identifying and prioritising specific research questions related to methodological uncertainties.
A modified e-Delphi process will be adopted. Participants (anticipated N=100) will include patients, clinicians, the public, researchers and others invested in creating a strategic research agenda for these reviews. This Delphi will be completed in four consecutive stages, including a survey collecting the methodological uncertainties for each of the big picture reviews, the development of research questions based on that survey and two further surveys and four workshops to prioritise the research questions.
This study was approved by the University of Adelaide Human Research Ethics Committee (H-2024-188). The results will be communicated through open-access peer-reviewed publications and conferences. Videos and infographics will be developed and placed on the JBI (previously Joanna Briggs Institute) Scoping Review Network webpage.
Lung cancer is increasingly being diagnosed in non-smokers, with mounting evidence that household air pollution is a potential factor. Environmental risk factors for lung cancer in never-smokers (LCINS) in relation to combustion of biomass for heating and cooking in low-middle-income countries (LMICs) have been extensively explored. However, such evidence in high-income countries (HICs) is limited. We conducted a systematic review to explore potential relationships between exposure to cooking fumes, a type of household air pollution, and lung cancer, specifically in relation to never-smokers in HICs.
Systematic review and narrative synthesis using the Critical Analysis Skills Programme (CASP) guidelines for case–control studies.
Embase, Scopus, the Cochrane library and CINAHL were searched, from inception to March 2024. Reference lists of articles were hand searched for additional papers.
Case–control studies focusing on household air pollution and its impact on LCINS in HICs were included.
Two independent reviewers searched, screened and coded included studies using a bespoke table. Quality of evidence was assessed in the selected studies using the CASP tool for case–control studies. Retained studies used different exposure assessment and reporting methods which were sufficiently heterogeneous to preclude meta-analysis; therefore, narrative synthesis was performed.
Three papers were included, with a total of 3734 participants. All studies were conducted in Taiwan or Hong Kong, focusing on Chinese women using traditional Chinese cooking methods. All three found a dose/response correlation between exposure to cooking fumes and the risk of developing LCINS.
Chen et al assessed the risk of lung cancer risk by ‘cooking time-years’, measuring exposure to cooking fumes over a participant’s lifetime, citing OR 3.17 (95% CI 1.34 to 7.68) for the highest levels of exposure. Yu et al used ‘cooking dish-years’ as a measure of exposure to cooking fumes, with OR 8.09 (95% CI 2.57 to 25.45) for the highest exposure levels, while Ko et al found that the number of dishes cooked daily was a greater indicator of risk than the number of cooking years, citing a threefold increased risk of lung cancer among women who cooked three meals per day compared with those who cooked one (OR 3.1, 95% CI 1.6 to 6.2).
Ventilation hoods were found to have a protective effect against LCINS with adjusted ORs of 0.49 (95% CI 0.32 to 0.76).
This review of three studies found a possible association between exposure to cooking fumes and the risk of developing LCINS in high-income settings. This corroborates the substantial body of evidence that links cooking fume exposure to LCINS in LMICs, with definitive confirmation of the exposure hazards.
CRD42024524445.
Inflammatory bowel diseases (IBDs) and multiple sclerosis (MS) are inflammatory diseases resulting from an interplay of genetic and environmental factors. This study aims to describe the prevalence of patients diagnosed with both conditions among those receiving hospital care in England, as well as the characteristics and healthcare resource use (HCRU) of such patients.
This study is a retrospective observational cohort study.
The study was conducted through secondary use of the English Hospital Episode Statistics (HES) Database. HES records care delivered by hospitals in England and associated diagnoses.
Patients who had a diagnosis code for either IBD or MS recorded in HES between January 2014 and May 2020 were included. Patients were classified as having each diagnosis individually or as having both diagnoses, in which case they were further categorised based on temporal occurrence.
The primary outcome was the prevalence of patients with a recorded diagnosis of either IBD, MS or both during the study period. Secondary outcome measures included patient demographic and clinical characteristics, as well as HCRU in the 6 months before and after the diagnosis of interest.
From an overall cohort of 352 698 patients, 1016 (0.3%) had both diagnoses. Among those with both, 29.8% (303) had a record of IBD first, 40.5% (411) had MS diagnosed first and 29.7% (302) had the first record of both diagnoses in the same episode. From the overall cohort, 80.9% (285 439) of patients had a single diagnosis of IBD, and 18.8% (66 243) of patients had a single diagnosis of MS.
The population with a dual diagnosis of IBD and MS is larger than previously reported and shows evidence of frequent interactions with secondary care.
Clinicians face challenges in implementing evidence-based practices due to limited resources and tools that can support their efforts in translating evidence into practice. To address this, JBI developed PACES (Practical Application of Clinical Evidence System), an online tool designed to streamline and support evidence implementation and quality improvement projects.
This paper reports the development of JBI-PACES and presents an evaluation of its usability (usefulness, satisfaction, ease of use) and user recommendations for improvements.
PACES was developed based on the integration of the Donabedian perspective on quality improvement and JBI's process model for evidence implementation, which incorporates context evaluation, facilitation of change, and the evaluation of both process and outcomes. Initially launched in 2004, the system underwent multiple enhancements based on informal user feedback from 2007 to 2017. A significant update, version 0.0.23 Build 1, was re-launched in late 2018. To evaluate its usability, we conducted a cross-sectional study using the Post-Study System Usability Questionnaire (PSSUQ), which also gathered qualitative feedback.
PACES supports evidence implementation by allowing users to conduct audits across multiple sites and over time, enabling data comparisons and insights into clinical practices. Findings from the usability evaluation showed high levels of satisfaction with the system's usefulness and ease of use. However, qualitative data indicated areas where further enhancements could optimize user experience and functionality.
The current study suggests clear benefits of PACES in terms of its utility and value for supporting evidence-based practices. Although the system performs well in usability, ongoing refinements are necessary to optimize user experience and ensure the tool continues to meet the evolving needs of healthcare professionals.
by Ian C. Lock, Nathan H. Leisenring, Warren Floyd, Eric S. Xu, Lixia Luo, Yan Ma, Erin C. Mansell, Diana M. Cardona, Chang-Lung Lee, David G. Kirsch
BackgroundThe tumor suppressor p53 (Trp53), also known as p53, is the most commonly mutated gene in cancer. Canonical p53 DNA damage response pathways are well characterized and classically thought to underlie the tumor suppressive effect of p53. Challenging this dogma, mouse models have revealed that p53-driven apoptosis and cell cycle arrest are dispensable for tumor suppression. Here, we investigated the inverse context of a p53 mutation predicted to drive the expression of canonical targets but is detected in human cancer.
MethodsWe established a novel mouse model with a single base pair mutation (GAG>GAT, p53E221D) in the DNA-Binding domain that has wild-type function in screening assays, but is paradoxically found in human cancer in Li-Fraumeni syndrome. Using mouse p53E221D and the analogous human p53E224D mutants, we evaluated expression, transcriptional activation, and tumor suppression in vitro and in vivo.
ResultsExpression of human p53E224D from cDNA translated to a fully functional p53 protein. However, p53E221D/E221D RNA transcribed from the endogenous locus is mis-spliced resulting in nonsense-mediated decay. Moreover, fibroblasts derived from p53E221D/E221D mice do not express a detectable protein product. Mice homozygous for p53E221D exhibited increased tumor penetrance and decreased life expectancy compared to p53WT/WT animals.
ConclusionsMouse p53E221D and human p53E224D mutations lead to splice variation and a biologically relevant p53 loss of function in vitro and in vivo.
To provide a description of nurses' experiences related to moral injury, including Potentially Morally Injurious Events and factors related to the impact of those events.
Reflexive thematic analysis of nurse interviews.
Nurses were recruited from an ongoing study within a large academic medical centre. Nurses who enrolled in the present study participated in semi-structured individual interviews using an interview guide based on Litz's conceptualisation of moral injury. Themes were identified in the recorded and transcribed interviews.
Interviews were conducted with 12 nurses in May and June 2023 and coded for themes within three broad categories: (a) Nursing Values, (b) Experiences of Potentially Morally Injurious Events and (c) Stressors and Supports. Within these categories, we pinpointed 8 themes and 3 subthemes, which highlight the nurses experience of potentially morally injurious events related to challenging care, strained relationships with physicians, and treatment inequity, which conflict with their nursing values. We identified team and organisational factors, including senior leadership behaviours, team dynamics and access to resources that appear to intensify or lessen the impact of these events.
Potentially Morally Injurious Events contribute to the occupational stress experienced by nurses, particularly when systemic organisational factors and demands prevent them from providing the value-driven and ethically necessary healthcare. Limiting Potentially Morally Injurious Events and providing supportive environments following stressors requires organisational-level changes within healthcare environments to prevent and alleviate nurses' occupational stress.
This research highlights the need for healthcare organisations to implement systemic interventions aimed both at reducing Potentially Morally Injurious Events and creating system and team-level supports to lessen the impact of unavoidable events. These results pinpoint specific areas for prevention, intervention and support.
No Patient or Public Contribution.
by Andrea Lear, Wesley Sheley, Jessy Shanks, Brian Whitlock, Chika Okafor
Small ruminants, including sheep and goats, play an important role in the economy of American agriculture. They are susceptible to a variety of diseases that impact animal welfare and production. This study evaluated postmortem data from two different diagnostic laboratories in the state of Tennessee to discern common causes of death of small ruminants that were brought in for necropsy between 2017 to 2021. Data were prepared for analysis by selecting the predominant conditions observed at postmortem examination and risk factors including sex, age, season, and region were included in analysis. The predominant condition seen in both small ruminant species was endoparasitism. In both sheep and goats, female juvenile animals were more likely to be diagnosed with this condition at necropsy during summer months. Abortive diseases were the next most prominent condition diagnosed in both small ruminant species. The majority of these cases were due to an unknown cause and age was a significant risk factor in both sheep and goats. Neurological disorders in goats and pneumonia in sheep were included in the most prevalent diagnoses at postmortem examination with age being a significant risk factor. These findings suggest that many small ruminant deaths are attributed to infectious diseases that have herdwide implications. Producer education could be beneficial to help identify and implement control measures in a timely manner to help minimize production loss associated with common diseases.To explore relatives' needs in terms of bereavement care during euthanasia processes, how healthcare providers respond to these needs, and the degree of commonality between relatives' and healthcare providers' reports.
A phenomenological design was employed, utilising reflexive thematic analysis to examine interviews conducted with relatives (N = 19) and healthcare providers (N = 47).
Relatives' needs throughout euthanasia processes are presented in five main themes and several subthemes, with similar findings between both sets of participants. Although relatives infrequently communicated their needs explicitly to healthcare providers, they appreciated it when staff proactively met their needs. Healthcare providers aimed to assist with the relatives' grief process by tending to their specific needs. However, aftercare was not consistently offered, but relatives did not have high expectations for professional follow-up care.
Our research offers important directions for healthcare professionals, empowering them to provide needs-based bereavement care during euthanasia processes. Moreover, it emphasises the importance of recognising the unique needs of relatives and proactively addressing them in the period before the loss to positively contribute to relatives' grief process.
Insights into relatives' needs in the context of euthanasia. Good practices on how healthcare providers can attend to relatives' needs before, during and after the loss
Current literature and guidelines on needs-based bereavement care in the context of euthanasia and, more generally, assisted dying, are limited. These findings provide concrete directions for practice in supporting (nearly) bereaved relatives in the context of euthanasia, potentially mitigating adverse health outcomes.
Standards for Reporting Qualitative Research (SRQR checklist).
Relatives of deceased cancer patients were involved in the conduct of the study.
To characterise experiences with telehealth for Medications for Opioid Use Disorder (MOUD) services among patients, prescribers, nurses and substance use counsellors to inform future best practices.
We engaged a qualitative descriptive study design.
Semi-structured interviews were conducted with prescribers (nurse practitioners and physicians, n = 20), nurses and substance use counsellors (n = 7), and patients (n = 20) between June and September 2021. Interviews were verbatim transcribed. Thematic analysis was conducted using a qualitative descriptive method.
Among both providers and patients, four themes were identified: (1) Difficulties with telehealth connection (2) Flexibility in follow-up and retention, (3) Policy changes that enabled expanded care, (4) Path forward with telehealth. Two additional findings emerged from provider interviews: (1) Expansion of nurse-managed office-based opioid treatment, and (2) Novel methods to engage patients.
Patients and providers continued to view telehealth as an acceptable means for delivery and management of MOUD, particularly when utilised in a hybrid manner between in-person visits. Nurse-managed care for this service was evident as nurses extended the breadth of services offered and utilised novel methods such as text messages and management of ‘call-in’ lines to engage patients.
Use of telehealth for MOUD should be incorporated into practice settings to reach patients in a flexible manner. Nurses in particular can use this medium to extend office-based opioid treatment by conducting assessments and expanding capacity for other wrap-around services.
We identify recommendations for best practices in the use of telehealth for opioid use disorder management and highlight the value of nurse-managed care.
The consolidated criteria for reporting qualitative research.
Patients with opioid use disorder and prescribers with experience using telehealth were interviewed for this study.