NIHR open research最新文献

Background: High blood pressure (BP) affects more than one in four adults in England and only one in three patients are being treated effectively. Treatment of high BP includes changes to lifestyle such as more physical activity and/or taking medication. However, low adoption and high attrition rates are common with current large targets for recommended exercise (>150 minutes moderate exercise per week plus 2 strength sessions). Evidence suggests that isometric exercise (IE), holding a fixed body position for a period of time, for example a wall squat, lowers BP a greater amount, with less time and effort, than other recommended exercise. This ISOFITTER study will provide robust effectiveness evidence of IE for hypertension.

Methods: A multi-centre, randomised, controlled trial of isometric exercise wall squat intervention for hypertension: an effectiveness-implementation hybrid type-1 design. Adults (n=542) with Stage 1 or Stage 2 hypertension, on no more than one antihypertensive, and no other medical contra-indications will be randomised to either a standard care plus IE intervention group or standard care control group. Blood pressure readings, fidelity measurements, medications, adverse events, quality of life, participant satisfaction and health service use will be collected at baseline, week 4, month 3 and month 6 with a subgroup of n=50 invited up to month 12. Qualitative participant focus groups and interviews with wider stakeholders will collect implementation data.

Results: The ISOFITTER study will establish effectiveness of a self-administered, home IE intervention in lowering blood pressure in people with uncomplicated stage 1 and 2 hypertension. Implementation evidence will support patient delivery, context for scaling up of the intervention and intervention cost.

Conclusion: Lifestyle changes for the treatment of hypertension in the absence of other risk factors should not be overlooked. For long term hypertension management, easily adopted, evidenced exercise interventions are needed. This study will help to address this evidence gap.

Introduction: In 2021 we launched the BronchStart study, which collected information on 17,899 hospital attendances in children with serious respiratory tract infections following the release of lockdown restrictions. Our study informed the Joint Committee on Vaccination and Immunisation's (JCVI) decision to recommend the introduction of maternal respiratory syncytial virus (RSV) vaccination, which was rolled out in the United Kingdom in August/September 2024 for all pregnant women at a gestation of 28 weeks or more. That winter we performed the BronchStop study, which examined vaccine effectiveness in its first season, conducted a survey of mothers to understand factors affecting vaccine uptake, and collected RSV positive samples for molecular epidemiology.

Methods and analysis: In the winter season of 2025-2026 we will conduct a UK-wide, multi-centre, prospective, test-negative case control study. The aim is to assess the effectiveness of maternal RSV vaccination against hospitalisation for RSV-associated acute lower respiratory tract infection (ALRI) amongst infants under the age of 6 months born to vaccine-eligible pregnant mothers. A survey designed in partnership with our public and patient involvement (PPI) group will be administered to mothers of recruited infants to understand factors affecting maternal vaccine uptake. RSV-positive samples will undergo whole genome sequencing, and all samples will undergo real-time, reverse transcriptase polymerase chain reaction (rRT-PCR) testing for a panel of respiratory viruses to understand residual causes of severe infant respiratory disease in the post-vaccination era.

Ethics and dissemination: Participants recruited to the study will be asked for informed consent to participate in the maternal survey, for researchers to access their vaccination records, and for routinely collected virological samples from their infants to undergo rRT-PCR testing. Regular reports to advisory groups, including JCVI and the World Health Organisation, and for peer-reviewed publications are planned to disseminate findings and inform decision-making.

Background: In addition to new antimicrobials for people with Cystic Fibrosis (pwCF), new diagnostics are needed to detect and diagnose infections, guide clinical care, and inform clinical decision making. To determine unmet diagnostic needs in pulmonary infection and exacerbation diagnostics in Cystic Fibrosis (CF), the required diagnostic test characteristics and priorities of different stakeholders involved in the care of pwCF were collected and analysed.

Methods: Three focus groups (two clinical and one pwCF) were conducted and used to inform a wider project to deliver a suite of target product profiles (TPPs) for CF lung microbiological infection and/or exacerbation diagnostics. Thematic analysis was performed on the focus group data.

Results: Participants described their experience of current practice and existing diagnostics for detection, diagnosis, and management of infection and exacerbations in CF in the UK National Health Service (NHS). Unmet needs included: monitoring modalities and testing for treatment efficacy; acquiring samples with good clinical utility; more acceptable sampling methods; and faster microbiology and culture-based testing.Greater communication between the laboratory and clinical teams, and equity of care across UK CF centres was also highlighted. TPP characteristics of importance to pwCF and clinical representatives included 'accuracy', 'time to results', and 'patient acceptability'. Both participants groups highlighted the need for suitable alternatives to sputum sampling and emphasised the need for novel biomarkers for the early detection and diagnosis of both infection and exacerbations. Amongst clinical representatives, test accuracy was generally valued over the time to results for a clinical test in a non-acute setting.

Conclusions: Focus groups offered rich and detailed insights into the opinions of clinical staff and pwCF alike which informed further stakeholder engagement and shaped the content, scope and characteristics of TPPs. Early and rapid detection would have a positive impact on clinical care and inform earlier clinical decision making.

Background: The National Institute for Health and Care Research (NIHR) is the UK's biggest funder for health and social care research, funded by the Department of Health and Social Care (DHSC). The NIHR infrastructure provides research expertise, specialist facilities, a research delivery workforce and support services, all of which help to support and deliver the research we fund, and research funded by others. The NIHR is committed to maximising the impact of the research we support and fund ¹ and therefore, it is crucial for the organisation to understand the mechanisms for the movement of research between these different pieces of research infrastructure and pathways to impact on the health and wealth of the nation. The aim of this article is to share our approach to developing an understanding of pathways to impact, enablers and barriers and lessons learnt.

Methods: We used publications reported to us by our infrastructure as receiving infrastructure support and forward and backward citation analysis to trace infrastructure support for REF 2021 impact case studies and research that has had an impact on policy. We used these data to develop impact case studies for NIHR infrastructure.

Results: Of the 6,361 REF impact case studies that are publicly available, the NIHR infrastructure has supported 327 of which 59 are supported by more than one scheme. Through our forward and backward citation analysis we have also developed impact case studies in the following NIHR priority areas:Reducing health inequalitiesDigital healthArtificial intelligenceWorkforce resilience.

Conclusions: The use of forward and backward citation analysis can also help research funders to understand how research is moving between different parts of their funding portfolios, pathways to impact and any gaps and opportunities. However, this comes with some challenges which need mitigation.

Introduction: Current sun safety advice focuses on minimizing exposure to sunlight, due to the relationship between ultraviolet radiation and skin cancer. However, sunlight also has beneficial effects, and there are calls for guidance to reflect these alongside the harmful effects. To examine the net effect of harmful and beneficial aspects, we aimed to determine the association between sunlight exposure and all-cause mortality. Additionally, we examined cause-specific mortality and whether the associations varied according to skin type/colour or ethnicity.

Methods: We conducted a systematic review, searching MEDLINE, Embase, Web of Science and the Cochrane Central Register of Controlled Trials (Nov 2023) for reports of epidemiological studies in the general population investigating the effect of long-term sun exposure on all-cause, cardiovascular-related, or cancer-related mortality. We conducted a narrative synthesis of the findings and assessed risk of bias using the ROBINS-E tool. PROSPERO: CRD42023474157.

Results: The search identified 73 eligible articles, with 55 included in the narrative synthesis. Methods of measuring sunlight exposure comprised radiation, proxy measures of radiation (e.g., latitude) and behaviour associated with sunlight exposure. The evidence was mixed. While most studies of skin cancer mortality found a higher risk associated with more exposure to sunlight, many studies of other cancers reported lower associated risk. Evidence for all-cause mortality was mixed, as were findings for cardiovascular mortality. Results were subject to high risk of bias, largely due to the likelihood of uncontrolled confounding and the use of indirect measures of sunlight exposure. There were insufficient data regarding any differential effects of sunlight on mortality for those of different skin types/colours or ethnicity.

Conclusion: Findings from observational epidemiological studies of the association between sunlight exposure and mortality vary across different disease outcome and location being investigated. As such, the findings do not provide a strong rationale for changes to sun protection guidance.

Background: Urinary tract infections (UTI) are the second most common serious bacterial infection in children. When healthcare practitioners are unsure if an infant, child, or young person has a UTI they perform a urine test. A midstream sample is recommended by the National Institute for Health and Care Excellence (NICE) for obtaining urine for testing. However, collecting urine from children who are unable to provide a midstream urine sample is challenging. Samples can be collected either by non-invasive (clean catch) or invasive methods (trans-urethral bladder catheter or suprapubic aspirate). Non-invasive methods are slow and prone to contamination but are painless. Invasive methods are less prone to contamination and are quick but can cause pain and distress.

Methods: This is a mixed methods feasibility study comprising of three parts. Part 1 is a pragmatic multicentre randomised controlled feasibility trial. The trial aims to evaluate the feasibility of conducting an RCT comparing invasive and non-invasive sampling methods for infants, children and young people (N = 100). Resource use will be assessed by parent reported questionnaire and mixed methods descriptors reported by healthcare professionals (n = 24). A cost analysis will assess the urine collection methods, informing a future cost-effectiveness analysis. Part 2 is an embedded mixed methods perspectives' study including interviews with parents (n = 15-20) and children (n = 10-15), five focus groups (n = 6-8 per group) and interviews (n = 10) with healthcare professionals aiming to assess feasibility and acceptability of the trial. Part 3 is a stakeholder (n = 40) consensus meeting determining a final definitive study design.

Discussion: The results of the study will inform a recommendation and decision on progression and design of a definitive RCT for infants, children and young people who have a suspected urine infection but cannot provide a midstream urine sample.

Trial registration: International Standard Randomised Controlled Trial Number (ISRCTN) 84676764: Feasibility of conducting a randomised controlled trial (RCT) comparing invasive and non-invasive urine sampling techniques in children under 16 years old with a suspected urinary tract infection ¹.

Background: This review examines whether randomised controlled trials (RCTs) of surgery in orthopaedics are inclusive of their target populations, including under-served populations.

Methods: The BMJ, Journal of the American Medical Association, The Lancet, and The New England Journal of Medicine were electronically searched in February 2022 for eligible RCTs published from 1 January 2014. Screening, key baseline patient characteristics, the inclusion of under-served groups and whether patient recruitment was pragmatic in design were key data extracted. The findings were tabulated and reported narratively.

Results: There were 26 RCTs included that were parallel in design and conducted across a range of countries in different hospital settings. Four RCTs did not report the complete CONSORT statement. There was variation in the percentage of the screened population who were randomised into the studies ranging from 5.8% to 74.7%. Most RCTs were pragmatic in design regarding patient selection but this did not necessarily translate to an inclusive trial population. Only two RCTs reported the age and gender of all screened patients. All 26 RCTs reported the age and gender of randomised patients but only four studies reported ethnicity. Reporting about the consideration and inclusion of under-served populations was limited.

Conclusions: There is variation in the exclusion of patients of the target population. Reporting of key patient characteristics during screening and attention given to under-served populations in the design, conduct and reporting of these trials is limited. Training and education on inclusivity is required along with practical guidance about how to implement this. To improve inclusivity in the screening and recruitment of patients there should be a focus on (i) screening and eligibility criteria, (ii) collection and reporting on attributes to ensure no section of the eligible population is inadvertently excluded, and (iii) embedding mechanisms to allow all eligible patients the opportunity to participate.

Background: Patient and Public Involvement (PPI) is a fundamental part of health research. The role of PPI in implementation research, which considers the transfer of evidence into practice, is often less well defined than in studies focussing on recruitment of individual patients and clinical outcomes, and there is limited guidance available. This paper uses an implementation research project, the Study of Implementation of Midwifery Continuity of Carer (SIMCA), to illustrate the types of activities, benefits, challenges and lessons learned to contribute to the development of this growing area.

Methods: The main aim of the PPI work in SIMCA was to embed the service user and community perspective in the study across all phases of the research, from preparation through execution and dissemination. Members of two organisations, one international and one community based, were core members of the study management team and PPI-driven activities were conducted throughout the study, incorporating both process and content focussed input.

Results: The key contributions of PPI to the study were identified as i) bringing experience and representation ii) providing connectivity between the team and the wider community iii) providing service user perspectives on study-related tasks iv) a developmental impact on the study team, improving awareness and challenging the dominant academic perspective. Several challenges are described, for example the ambiguity of the role.

Discussion: The SIMCA study has been used to illustrate the significant contributions that PPI can make to an implementation study and to the study team culture, in particular the value of having different perspectives within the team to ensure the study does not become too far removed from lived experience. Dilemmas related to the blurring between PPI and data collection and the need for more theoretical understanding of PPI in implementation research to make the findings more generalisable.

Context: In social care research economic evaluation has had limited impact, in contrast to other health related areas. However, increasing research funding and policy interest is occurring, including regarding the role of cost-effectiveness decision modelling.

Objectives: We explore why cost-effectiveness decision modelling is informative in a social care setting, how it can and has previously been implemented, and what next steps are needed to ensure consistent, robust, and informative models are produced to inform social care decisions.

Method: This paper consists of an overview of the theoretical added value of cost-effectiveness decision modelling in a social care setting, alongside a literature search summarising the key features of decision models in the current published and grey literature.

Findings: Cost-effectiveness decision modelling in social care is relatively undeveloped with only a few examples identified and minimal methodological research in the area. These studies varied greatly in the approaches taken but demonstrate the practicality and value of decision modelling.

Limitations: The pragmatic approach to the literature review may have missed some existing decision models but we consider the findings to be appropriate.

Implications: Cost-effectiveness decision modelling has the potential to play an important role in informing effective, consistent, and transparent decision-making processes in social care. However, methodological developments are needed to standardise the approaches taken.

Background: Good quality shared decision-making (SDM) conversations involve people with, or at risk of osteoporosis and clinicians collaborating to decide, where appropriate, which evidence-based medicines best fit the person's life, beliefs, and values. We developed the improving uptake of Fracture Prevention drug treatments (iFraP) intervention comprising a computerised Decision Support Tool (DST), clinician training package and information resources, for use in UK Fracture Liaison Service consultations. Two primary objectives to determine (1) the effect of the iFraP intervention on patient-reported ease in decision-making about osteoporosis medicines, and (2) cost-effectiveness of iFraP intervention compared to usual NHS care. Secondary objectives are to determine the iFraP intervention effect on patient reported outcome and experience measures, clinical effectiveness (osteoporosis medicine adherence), and to explore intervention acceptability, mechanisms, and processes underlying observed effects, and intervention implementation.

Methods: The iFraP trial is a pragmatic, parallel-group, individual randomised controlled trial in patients referred to a Fracture Liaison Service, with nested mixed methods process evaluation and health economic analysis. Participants aged ≥50 years (n=380) are randomised (1:1 ratio) to one of two arms: (1) iFraP intervention (iFraP-i) or (2) comparator usual NHS care (iFraP-u) and are followed up at 2-weeks and 3-months. The primary outcome is ease of decision-making assessed 2 weeks after the consultation using the Decisional Conflict Scale (DCS). The primary objectives will be addressed by comparing the mean DCS score in each trial arm (using analysis of covariance) for patients given an osteoporosis medicine recommendation, alongside a within-trial cost-effectiveness and value of information (VoI) analysis. Process evaluation data collection includes consultation recordings, semi-structured interviews, and DST analytics.

Discussion: The iFraP trial will answer important questions about the effectiveness of the new 'iFraP' osteoporosis DST, coupled with clinician training, on SDM and informed initiation of osteoporosis medicines.

Trial registration: ISRCTN 10606407, 21/11/2022 https://doi.org/10.1186/ISRCTN10606407.