A feasibility, randomised controlled trial of a complex breathlessness intervention in idiopathic pulmonary fibrosis (BREEZE-IPF): study protocol

Introduction Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease that causes breathlessness and cough that worsen over time, limiting daily activities and negatively impacting quality of life. Although treatments are now available that slow the rate of lung function decline, trials of these treatments have failed to show improvement in symptoms or quality of life. There is an immediate unmet need for evidenced-based interventions that improve patients' symptom burden and make a difference to everyday living. This study aims to assess the feasibility of conducting a definitive randomised controlled trial of a holistic, complex breathlessness intervention in people with IPF. Methods and analysis The trial is a two-centre, randomised controlled feasibility trial of a complex breathlessness intervention compared with usual care in patients with IPF. 50 participants will be recruited from secondary care IPF clinics and randomised 1:1 to either start the intervention within 1 week of randomisation (fast-track group) or to receive usual care for 8 weeks before receiving the intervention (wait-list group). Participants will remain in the study for a total of 16 weeks. Outcome measures will be feasibility outcomes, including recruitment, retention, acceptability and fidelity of the intervention. Clinical outcomes will be measured to inform outcome selection and sample size calculation for a definitive trial. Ethics and dissemination Yorkshire and The Humber – Bradford Leeds Research Ethics Committee approved the study protocol (REC 18/YH/0147). Results of the main trial and all secondary end-points will be submitted for publication in a peer-reviewed journal

A TRAIL-R1-specific ligand in combination with doxorubicin selectively targets primary breast tumour cells for apoptosis

A TRAIL-R1-specific ligand in combination with doxorubicin selectively targets primary breast tumour cells for apoptosi

high INtensity Interval Training In pATiEnts with intermittent claudication (INITIATE):a qualitative acceptability study

INTRODUCTION: A novel high-intensity interval training (HIIT) programme has demonstrated feasibility for patients with intermittent claudication (IC). The aim of this study was to explore patient perspectives of the HIIT programme to inform refinement and future research.METHODS: All patients screened and eligible for the 'high intensity interval training in patients with intermittent claudication (INITIATE)' study, were eligible to take part in a semi-structured interview. A convenience subsample of patients was selected from three distinct groups: 1) those who completed the HIIT programme, 2) those who prematurely discontinued the HIIT programme and 3) those who declined the HIIT programme. Interviews considered patients views of the programme and experiences of undertaking and/or being invited to undertake it. Interviews were audio recorded, transcribed verbatim and analysed via thematic analysis.RESULTS: Eleven out of 31 participants who completed the programme and twelve out of 38 decliners were interviewed. No participants who withdrew from the programme agreed to interview. The three key themes were; personal reflections of the programme; programme facilitators and barriers; and perceived benefits. Completers enjoyed taking part, reported symptomatic improvement and would complete it again. Practical and psychological barriers exist, such as transport and motivation. Changes to the programme were suggested.CONCLUSION: Findings support the acceptability of this novel HIIT programme, which in combination with the feasibility findings, suggest that a fully powered randomised controlled trial, comparing HIIT to usual-care supervised exercise programmes is warranted.</p

High INtensity Interval Training In pATiEnts with intermittent claudication (INITIATE): protocol for a multicentre, proof-of-concept, prospective interventional study

INTRODUCTION: The first-line recommended treatment for patients with intermittent claudication (IC) is a supervised exercise programme (SEP), which includes a minimum of 2-hours of exercise per week over a 12-week period. However, provision, uptake and adherence rates for these SEP programmes are poor, with time constraints cited as a common participant barrier. High-intensity interval training (HIIT) is more time-efficient and therefore has the potential to overcome this barrier. However, evidence is lacking for the role of HIIT in those with IC. This proof-of-concept study aims to consider the safety, feasibility, tolerability and acceptability of a HIIT programme for patients with IC. METHODS AND ANALYSIS: This multicentre, single-group, prospective, interventional feasibility study will recruit 40 patients with IC, who will complete 6 weeks of HIIT, 3 times a week. HIIT will involve a supervised programme of 10×1 min high-intensity cycling intervals at 85%-90% peak power output (PPO), interspaced with 10×1 min low intensity intervals at 20%-25% PPO. PPO will be determined from a baseline cardiopulmonary exercise test (CPET) and it is intended that patients will achieve ≥85% of maximum heart rate from CPET, by the end of the second HIIT interval. Primary outcome measures are safety (occurrence of adverse events directly related to the study), programme feasibility (including participant eligibility, recruitment and completion rates) and HIIT tolerability (ability to achieve and maintain the required intensity). Secondary outcomes include patient acceptability, walking distance, CPET cardiorespiratory fitness measures and quality of life outcomes. ETHICS AND DISSEMINATION: Ethical approval was obtained via a local National Health Service research ethics committee (Bradford Leeds - 18/YH/0112) and recruitment began in August 2019 and will be completed in October 2020. Results will be published in peer-reviewed journals and presented at international conferences and are expected to inform a future pilot randomised controlled trial of HIIT versus usual-care SEPs. TRIAL REGISTRATION NUMBER: NCT04042311; Pre-results

Families’ perceptions of and experiences related to a pediatric weight management program.

Objective: To examine parents' and children's perceptions of and experiences related to a Parents as Agents of Change (PAC) intervention for managing pediatric obesity. Methods: Ten families were recruited from a PAC intervention. Participants were interviewed before (10 adults and 9 children), during (9 adults and 8 children), and after (8 adults) the intervention. Results: Before the intervention, families reported goals to increase physical activity, plan and eat healthier meals, reduce screen time, and lose weight. During the intervention, families described different approaches to making behavior changes depending on who assumed responsibility (parent, child, or shared responsibility). After the intervention, group setting, goal setting, and portion size activities were viewed positively. Suggestions for improvement included engaging children and reducing intervention length. Conclusions and Implications: Practitioners delivering PAC interventions should discuss families' goals and concerns, and who is responsible for making lifestyle changes. Practical activities are valuable. The length of interventions and engagement of children should be considere

Exploring the Contextual Assumptions, Interventions, and Outcomes of Digital Advance Care Planning Systems: A Theory of Change Approach to Understand Implementation and Evaluation

Background: Digital advance care planning systems are used internationally to document and share patients’ wishes and preferences to inform care delivery. However, their use is impeded by a limited understanding of factors influencing implementation and evaluation. Aim: To develop mid-range programme theory to account for technological, infrastructure and human factor influences on digital advance care planning systems. Design: Exploratory qualitative research design incorporating Theory of Change workshops that explored contextual assumptions affecting digital advance care planning in practice. A mid-range programme theory was developed through thematic framework analysis using the Non-adoption, Abandonment, Scale-up, Spread, and Sustainability (NASSS) framework, generating a conceptual model depicting contextual assumptions, interventions and outcomes influencing implementation. Participants: 38 participants (16 from London, 14 from West Yorkshire, and eight online) including patients, carers, and health and care professionals (including those with commissioning responsibilities). Results: A conceptual model was generated depicting five distinct components relating to digital advance care planning system use: (sociocultural, technical, and structural prerequisites; recognition of the clinical need for conversation; having conversations and documenting decisions; accessing, actioning, and amending; and using data to support evaluation, use, and implementation). There were differences and uncertainty relating to what digital advance care planning systems are, who they are for, and how they should be evaluated. Conclusions: Digital advance care planning lacks shared beliefs and practices, despite these being essential for complex technology implementation. Our mid-range programme theory can guide their further development and application by considering technological, infrastructure and human factor influences to optimise their implementation

Laparoscopic versus open colorectal surgery in the acute setting (LaCeS trial): a multicentre randomized feasibility trial

AbstractBackgroundApproximately 30,000 people per annum undergo major, emergency abdominal, gastrointestinal surgery, of which 36% (~10,800) are carried out for emergency colorectal pathology. Approximately 14% of all patients requiring emergency surgery undergo laparoscopic surgery. AimsThe aims of the LaCeS feasibility trial (Laparoscopic versus Open Colorectal Surgery in the Acute Setting) were to assess the feasibility, safety and acceptability of performing a large-scale definitive phase III randomised controlled trial with a comparison of emergency laparoscopic with open surgery for acute colorectal pathology. MethodsLaCeS was designed as a prospective, multicentre, single blind, parallel group, pragmatic, randomised controlled feasibility trial with an integrated qualitative study. Randomisation was performed centrally with patients being randomised on a 1:1 basis between laparoscopic or open surgery. ResultsA total of 64 patients were recruited across 5 centres. The overall average steady state recruitment rate was 1.2 patients/month. Baseline compliance for clinical and HrQoL data was 99.8% and 93.8% respectively. The conversion rate from laparoscopic to open surgery was 39.4% (95% CI 22.9% – 57.9%). The 30 day post-operative complication rate was 27.3% (95% CI 13.3- 45.5) in the laparoscopic arm and 41.9% (95% CI 24.6 – 60.9) in the open arm. DiscussionThe LaCeS feasibility trial has demonstrated that it is possible to evaluate laparoscopic surgery in the emergency colorectal setting within the context of a randomised controlled trial. LaCeS has demonstrated that it is possible to recruit to a surgical trial in the emergency setting, with good compliance to trial procedures and processes, and overall acceptability by patients and clinicians. The safety data obtained for laparoscopic emergency colorectal surgery indicate an acceptable safety profile, particularly when considering it to that observed in the open arm.Trial Registration ISRCTN15681041 https://doi.org/10.1186/ISRCTN15681041.Funding body: National Institute of Health Research – Research for Patient Benefi

Searching for Programme theories for a realist evaluation: a case study comparing an academic database search and a simple Google search

Background: Realist methodologies are increasingly being used to evaluate complex interventions in health and social care. Programme theory (ideas and assumptions of how a particular intervention works) development is the first step in a realist evaluation or a realist synthesis, with literature reviews providing important evidence to support this. Deciding how to search for programme theories is challenging and there is limited guidance available. Using an example of identifying programme theories for a realist evaluation of Pressure Ulcer Risk Assessment Instruments in clinical practice, the authors explore and compare several different approaches to literature searching and highlight important methodological considerations for those embarking on a programme theory review. Methods: We compared the performance of an academic database search with a simple Google search and developed an optimised search strategy for the identification primary references (i.e. documents providing the clearest examples of programme theories) associated with the use of Pressure Ulcer Risk Assessment Instruments (PU-RAIs). We identified the number of primary references and the total number of references retrieved per source. We then calculated the number needed to read (NNR) expressed as the total number of titles and abstracts screened to identify one relevant reference from each source. Results: The academic database search (comprising CINAHL, The Cochrane Library, EMBASE, HMIC, Medline) identified 2 /10 primary references with a NNR of 1395.The Google search identified 7/10 primary references with a NNR of 10.1. The combined NNR was 286.3. The optimised search combining Google and CINAHL identified 10/10 primary references with a NNR of 40.2. Conclusion: The striking difference between the efficiency of the review’s academic database and Google searches in finding relevant references prompted an in-depth comparison of the two types of search. The findings indicate the importance of including grey literature sources such as Google in this particular programme theory search, while acknowledging the need for transparency of methods. Further research is needed to facilitate improved guidance for programme theory searches to enhance practice in the realist field and to save researcher time and therefore resource

Participant engagement with a UK community-based preschool childhood obesity prevention programme: : a focused ethnography study

Background Children’s centres in the UK provide a setting for public health programmes; offering support to families living in the most disadvantaged areas where obesity prevalence is at its highest. Health, Exercise and Nutrition in the Really Young (HENRY) is an eight-week obesity prevention programme currently delivered in children’s centres across the UK. However, low participant engagement in some local authorities threatens its potential reach and impact. This study aimed to explore the factors influencing participant engagement with HENRY to describe where local intervention may support engagement efforts. Method A focused ethnography study was undertaken in five children’s centres delivering HENRY across the UK. One hundred and ninety hours of field observations, 22 interviews with staff (commissioners, HENRY co-ordinators, managers and facilitators) and six focus groups (36 parents), took place over five consecutive days in each centre. The Consolidated Framework for Implementation Research (CFIR) was used to guide the observations and analysis of the data. Results Three overarching themes described the factors influencing participant engagement with HENRY: local authority decision making around children’s centre programmes; children’s centre implementation of HENRY; and the participant experience of HENRY. The results indicate that factors influencing participant engagement with public health programmes begin at the commissioning body level, influencing children’s centre implementation and subsequently the experience of participants. Local authority funding priorities and constraints influence availability of places and who these places are offered to, with funding often targeted towards those deemed most at need. This was perceived to have a detrimental effect on participant experience of the programme. Conclusion In summary, participant engagement is affected by multiple factors, working at different levels of the children’s centre and local authority hierarchy, most of which are at play even before participants decide whether or not they choose to enrol and maintain attendance. For programmes to achieve their optimal reach and impact, factors at the commissioning and local implementation level need to be addressed prior to addressing participant facing issues

Enhanced Hsp70 Expression Protects against Acute Lung Injury by Modulating Apoptotic Pathways

The Acute respiratory distress syndrome (ARDS) is a highly lethal inflammatory lung disorder. Apoptosis plays a key role in its pathogenesis. We showed that an adenovirus expressing the 70 kDa heat shock protein Hsp70 (AdHSP) protected against sepsis-induced lung injury. In this study we tested the hypothesis that AdHSP attenuates apoptosis in sepsis-induced lung injury