National Institute For Health Research Research Articles

4.F. Scientific session: Progress in assessing climate change risks to health and implementation in UK and Europe

Abstract Climate change poses one of the greatest threats to health security. Climate change is increasing the frequency and intensity of environmental health threats like flooding and heatwaves and is creating conditions which heighten the risks from infectious diseases. Whilst everyone will be at some risk from adverse health impacts from climate change, the impacts will vary at individual level and the most disadvantaged both here in the UK and around the world will be disproportionately affected. Many of the anticipated adverse health impacts of climate change in the UK are still avoidable through mitigation and adaptation and that there are other benefits to health to be gained, therefore rapid action is critical to avoid the most severe potential scenarios. The Health Protection Research Unit in Environmental Change and Health, funded by the National Institute of Health Research, provides multi-disciplinary research to support decision-making relating to the impacts and responses to environmental changes that affect human health and well-being in the UK and beyond. In this workshop we present the results of recent research on the progress in assessing climate change risk factors on health in the UK and review the evidence on implementation of mitigation and adaptation measures in Europe. The workshop aims to support evidence translation for climate action that prioritises health protection and equity. The workshop will include presentations on reviewing risk assessment methods for quantifying health impacts across Europe as well as analysing the effects of fuel poverty on cold-related mortality. We present results from an analysis of primary care data to identify individual level characteristics associated with increased risk of mortality during heatwaves. Furthermore, we review national food-based dietary guidelines across Europe and South America to determine how environmental sustainability is being integrated to benefit health. The workshop will comprise 4 -5 oral presentations and we will then open the floor to have a wider facilitated discussion about what are the evidence needs for UK and European policy to further address climate risks to health. Key messages • The progress in assessment and understanding of risks from climate change on health is improving. • The health risks we face from climate change will not be distributed equally across the UK and Europe.

Association between Scabies Treatment and Parkinson's Disease: A Nationwide, Population-Based Study.

Scabies is typically treated with scabicides like lindane, which poses a risk for acute neural toxicity. Lindane's prolonged use, particularly in agriculture, is linked to neurodegenerative diseases, including Parkinson's disease (PD), the second most common neurodegenerative disorder. This study aimed to evaluate whether scabies patients, particularly those treated with topical lindane, are at increased risk of developing PD. A nationwide population-based cohort study was conducted using data from Taiwan's National Health Research Institutes claims database from 2000 to 2018. The study included 27,173 patients with scabies, matched to a control group, with both groups followed for up to 18 years. The primary outcome was the incidence of newly diagnosed PD, and the hazard ratio (HR) for PD was calculated, focusing on those treated with topical lindane. Among the 54,346 patients, 1639 (3.0%) were newly diagnosed with PD, with 993 (60.6%) from the scabies group and 646 (39.4%) from the control group. Scabies patients had an adjusted hazard ratio (aHR) of 1.46 (95% CI 1.32-1.63) for developing PD compared to controls. However, patients treated with topical lindane had a significantly lower aHR for PD at 0.15 (95% CI 0.12-0.19; p < 0.001), with a lower cumulative incidence of PD also observed in this group (p < 0.001). Scabies patients are at a 1.46-fold increased risk of developing PD, but those treated with lindane exhibit a significantly lower risk, suggesting potential protective effects of lindane against PD.

Combined interventions for the testing and treatment of HIV and schistosomiasis among fishermen in Malawi: a three-arm, cluster-randomised trial

Undiagnosed HIV and schistosomiasis are highly prevalent among fishermen in the African Great Lakes region. We aimed to evaluate the efficacy of lakeside interventions integrating services for HIV and male genital schistosomiasis on the prevalence of schistosomiasis, uptake of antiretroviral therapy (ART) for HIV, and voluntary male medical circumcision (VMMC) among fishermen in Malawi. We conducted a three-arm, cluster-randomised trial in 45 lakeshore fishing communities (clusters) in Mangochi, Malawi. Clusters were defined geographically by their home community as the place where fishermen leave their boats (ie, a landing site). Eligible participants were male fishermen (aged ≥18 years) who resided in a cluster. Clusters were randomly allocated (1:1:1) through computer-generated random numbers to either enhanced standard of care (SOC), which offered invitation with information leaflets to a beach clinic offering HIV testing and referral, and presumptive treatment for schistosomiasis with praziquantel; peer education (PE), in which a nominated fisherman was responsible for explaining the study leaflet to promote services to his boat crew; or peer distribution education (PDE), in which the peer educator explained the leaflet and distributed HIV self-test kits to his boat crew. The beach clinic team and fishermen were not masked to intervention allocation; however, investigators were masked until the final analysis. Coprimary composite outcomes were the proportion of participants who had at least one Schistosoma haematobium egg observed on light microscopy from 10 mL of urine filtrate and the proportion who had self-reported initiating ART or scheduling VMMC by day 28. Outcomes were analysed by intention to treat; multiple imputation for missing outcomes was done; random-effect binomial models adjusting for baseline imbalance and clustering were used to compute unadjusted and adjusted risk differences, risk ratios (RRs) and 95% CIs, and intracluster correlation coefficients for each outcome. This trial is registered with ISRCTN, ISRCTN14354324. Between March 1, 2022, and Jan 29, 2023, 45 (65·2%) of 69 clusters assessed for eligibility were enrolled in the trial, with 15 clusters per arm. Of the 6036 fishermen screened at baseline, 5207 (86·3%) were eligible for participation: 1745 (87·6%) of 1991 in the enhanced SOC group, 1687 (81·9%) of 2061 in the PE group, and 1775 (89·5%) of 1984 in the PDE group. Compared with the prevalence of active schistosomiasis in the enhanced SOC group (292 [16·7%] of 1745), 241 (13·6%) of 1775 fishermen in the PDE group (adjusted RR 0·80 [95% CI 0·69-0·94]; p=0·0054) and 263 (15·6%) of 1687 fishermen in the PE group (0·92 [0·79-1·07]; p=0·28) had schistosomiasis at day 28. 230 (13·2%) in the enhanced SOC group, 281 (16·7%) in the PE group, and 215 (12·1%) in the PDE group initiated ART or were scheduled for VMMC. ART initiation or VMMC scheduling was not significantly increased with the PDE intervention (0·88 [0·74-1·05); p=0·15) and was marginally increased with the PE intervention (1·16 [0·99-1·37]; p=0·069) when compared with the enhanced SOC group. No serious adverse events were reported in this trial. We found weak evidence for the use of peer education to increase uptake of ART and VMMC, but strong evidence for the added distribution of HIV self-test kits to promote high engagement with services and reduce the prevalence of active schistosomiasis, suggesting a high potential for scale-up in hard-to-reach communities across Malawi. Wellcome Trust and the UK National Institute for Health Research.

The effectiveness of relaxation exercises on fatigue in hemodialysis patients: a meta-analysis study.

This study was conducted to determine the effect of relaxation exercise on fatigue symptoms in hemodialysis patients. This is a meta-analysis study. The literature review was carried out by searching studies published between 2011 and 2020. This meta-analysis was recorded on PROSPERO in the National Health Research Institute (Registration no: CRD42022313646). Seven studies meeting the inclusion criteria were included in the meta-analysis. The effect size of the studies included in the meta-analysis was found to be g=1.232 (p=0.028), which indicated a "huge effect size." The scale used in the subgroup analyses, the application time of the relaxation exercise, and the number of relaxation exercise applications were evaluated, and a significant difference was found at p<0.05. Relaxation exercises can be used as an effective method for reducing fatigue in hemodialysis patients.

The relationship between radiation oncology department NIH funding and institutional community inclusion/investment.

153 Background: Disparities in healthcare access and funding allocation persist among racial minorities and low-income populations. Radiation Oncology departments play a crucial role in cancer treatment, yet the extent to which these departments serve historically underrepresented communities following receipt of National Institutes of Health (NIH) funding remains unclear. This study accessed the relationship between radiation oncology departments that are awarded National Institute of Health (NIH) funding and Lown Institute Hospitals Index rankings for community benefit and inclusivity. Methods: Radiation oncology departments awarded funding from the NIH from 2019-2021 were retrospectively studied. The 2023 Lown Institute Hospital Index rankings for community benefit and inclusivity were examined. The community benefit metric measures financial assistance spending, community investment spending, and Medicaid as a portion of patient revenue. The inclusivity metric measures the similarities of income, race, and education level between the hospital patient population and the surrounding community. Kendall’s correlation coefficient (tau value) and linear regression were used to evaluate the relationship between measures of community benefit and inclusivity and NIH radiation oncology department research funding. Results: Twenty-two radiation oncology departments that received NIH funding (median = $ 419,555.00) were included. A statistically significant positive correlation was observed between the amount of radiation oncology NIH research funding received and institutional rankings for overall community benefit (tau = 0.378; P &lt; 0.034), with a trend towards significance for institutional rankings for community investment spending (tau = 0.497; P &lt; 0.053). No significant correlation was observed between the amount of radiation oncology department funding and institutional rankings for charity care spending (P = 0.430), Medicaid as a portion of patient revenue (P = 0.837), and service of patients from racial and or ethnic minorities (P = 0.505), with low income (P = 0.612), or with lower levels of education (P = 0.700). Conclusions: Our study highlights the relationship between recent NIH funding received by Radiation Oncology departments and their commitment to community health and inclusivity. Our findings indicate a significantly positive correlation between NIH funding received by radiation oncology departments and overall community benefit. This suggests that departments receiving NIH funding may be incentivized to allocate resources towards initiatives to improve community health outcomes beyond direct patient care. This study prompts further exploration into the mechanisms through which NIH-funded radiation oncology departments allocate resources and engage with their surrounding communities.

Relationship Between Radiation Oncology Department National Institutes of Health Funding and Institutional Community Inclusion/Investment

PURPOSE Disparities in health care access and funding allocation persist among racial minorities and low-income populations. Radiation oncology departments play a crucial role in cancer treatment, yet the extent to which these departments serve historically underrepresented communities following receipt of National Institutes of Health (NIH) funding remains unclear. METHODS Radiation oncology departments awarded NIH funding from 2019 to 2021 were studied using the 2023 Lown Institute Hospital Index rankings for community benefit and inclusivity to assess the relationship between measures of community benefit and inclusivity and NIH radiation oncology department research funding. RESULTS Twenty-two radiation oncology departments were analyzed in this study. A significant positive correlation was identified between the NIH research funding these departments received and their institutional rankings for overall community benefit (tau = 0.38; P &lt; .034). Additionally, there was a trend toward significance for the relationship between NIH funding and institutional rankings for community investment spending (tau = 0.497; P &lt; .053). No significant correlation was observed for other variables, including institutional rankings for charity care spending, Medicaid as a portion of patient revenue or services provided to patients from minoritized groups, low-income backgrounds, or those with lower levels of education. CONCLUSION Our findings indicate a significantly positive correlation between NIH funding received by radiation oncology departments and overall community benefit (measured by spending on financial assistance, community investment, and Medicaid). This suggests that departments receiving NIH funding may be incentivized to allocate resources toward initiatives aimed at improving community health outcomes extending beyond direct patient care.

Hyaluronic Acid in Bone Regeneration: Systematic Review and Meta-Analysis.

The aim of this systematic review and meta-analysis was to assess possible histomorphometric differences in new bone formation and in remaining graft particles when hyaluronic acid (HA) was added and mixed with graft materials in bone regeneration. This review was registered at the International Prospective Register of Systematic Reviews (PROSPERO) of the National Institute of Health Research (registration number CRD42024530030). Electronic research was performed, and involved studies published up to 29 February 2024 using a specific word combination. The primary outcome was to assess possible histomorphometric differences in new bone formation and in remaining graft particles when HA was added and mixed with graft materials in bone regeneration. The search resulted in 138 potential studies. Meta-analyses were performed using the fixed and random effects model to identify significant changes in new bone formation and in the remaining graft particles. After screening procedures, only three randomized controlled trials fulfilled the inclusion criteria and were selected for qualitative and quantitative analysis. The effect size of HA in the new bone formation was not statistically significant at 95% CI (Z = 1.734, p-value = 0.083, 95 % CI -,399; 6516). The effect size of HA in the remaining graft particles was not statistically significant at 95% CI (Z = -1.042, p-value = 0.297, CI -,835; 255). Within the limitations of the present systematic review and meta-analysis, the addition of HA to bone graft did not result in significant changes in bone regeneration procedures in terms of new bone formation and residues, even if the included studies showed encouraging and promising results.

Evaluating Research Activity and NIH-Funding Among Academic Ophthalmologists Using Relative Citation Ratio

ABSTRACT Purpose The objective of this study was to evaluate the relationship between research activity and National Institutes of Health (NIH) funding status of the United States (US) academic ophthalmologists. Methods A retrospective cross-sectional analysis of bibliometric data was conducted. The NIH Research Portfolio Online Reporting Tools Expenditures and Reports (rePORTER) website was utilized to identify ophthalmology departments in the US that received NIH funding. Affiliated faculty from these institutions were then identified using NIH rePORTER and institutional websites. H-index was calculated using the Scopus database, and the NIH iCite tool was used to determine the Relative Citation Ratio (RCR). The h-index and w-RCR quantified research productivity, while m-RCR measured research impact. Results Data on 2688 faculty members from 66 departments we re identified, of which 21% were NIH-funded. Faculty members who received NIH-funding had significantly greater research productivity and impact as measured by h-index (32.5 vs 16.6; p < .001), m-RCR (2.2 vs 1.6; p < .001), and w-RCR (147.2 vs 70.1; p < .001) than their non-funded peers. When stratified by academic rank, NIH-funded faculty still had significantly higher h-index (16.1 vs 7.9; p < .001), m-RCR (2.2 vs 1.4; p < .001), and w-RCR (63.2 vs 61.8; p < .001) than non-funded peers. A similar trend was observed among non-tenured faculty members. Conclusion NIH funding is associated with higher research productivity and impact among US academic ophthalmologists as measured by h-index and RCR, which suggests that NIH funding may be a critical factor in enhancing scholarly contributions of ophthalmologists. These findings underscore the importance of continued investment in NIH funding to foster high-impact research within the field of ophthalmology.

Potential impact of replacing the 13-valent pneumococcal conjugate vaccine with 15-valent or 20-valent pneumococcal conjugate vaccine in the 1 + 1 infant schedule in England: a modelling study

Paediatric pneumococcal conjugate vaccine (PCV) programmes in England using seven-valent PCV (PCV7) in 2006 and 13-valent PCV (PCV13) in 2010 have reduced vaccine-type invasive pneumococcal disease, but the overall effect has been reduced by an increase in invasive pneumococcal disease due to non-vaccine serotypes and serotype 3. We developed pneumococcal transmission models to investigate the potential effect on invasive pneumococcal disease of higher valency PCVs covering an additional two (ie, 15-valent PCV [PCV15]) or seven serotypes (ie, 20-valent PCV [PCV20]) in England. We conducted a modelling study using realistic, age-structured, and compartmental deterministic models fitted to carriage data from before the introduction of PCVs and invasive pneumococcal disease data from before and after the introduction of PCV7 and PCV13 in England from the UK Heath Security Agency invasive pneumococcal disease surveillance system. We estimated key parameters, including PCV7 and PCV13 efficacy against vaccine-type carriage and invasiveness of PCV7 serotypes; the additional serotypes in PCV13, PCV15 and PCV20; and non-vaccine serotypes. We simulated the effect of transitioning from PCV13 to PCV15 or PCV20 in infants under the current 1 + 1 vaccination schedule and investigated the effect of reduced carriage protection against PCV13 serotypes due to attenuation of immunogenicity in higher valency vaccines. Our results suggest that PCV15 might increase overall invasive pneumococcal disease as the reduction in vaccine-type invasive pneumococcal disease would be counterbalanced by an increase in non-PCV15 invasive pneumococcal disease. By contrast, PCV20 is projected to have a substantial impact on overall invasive pneumococcal disease due to higher invasiveness of the additional serotypes covered by PCV20 than the replacing non-vaccine serotypes. Reduced carriage protection against PCV13 serotypes with higher valency vaccines would amplify these effects. Replacing PCV13 with PCV20 is likely to have a substantial public health benefit, but PCV15 could potentially increase the overall burden of disease. UK Health Security Agency and National Institute of Health Research.

CHARACTERISTICS OF SCIATICA PATIENTS LISTED FOR A SPINAL EPIDURAL STEROID INJECTION AND CLINICAL OUTCOMES: RESULTS FROM THE POISE COHORT STUDY

BackgroundClinical guidelines recommend epidural steroid injection (ESI) for severe sciatica but there is uncertainty of effectiveness. The POiSE study aims to identify factors, routinely collected in clinical practice that predict outcome in patients who have ESI. This presentation describes characteristics and early clinical outcomes of POiSE participants.MethodsProspective cohort study in 19 NHS spinal services in England, inviting patients with sciatica listed for an ESI. Participant baseline characteristics and 6-week follow-up outcomes are presented. Outcomes include pain intensity (0–10 NRS), disability (Oswestry Disability Index 0–100) and global change in symptoms.ResultsOver 24 months, 693 patients were invited to participate and 353 (51%) completed baseline questionnaires. Mean (SD) age 49.0 years (14.4), 60% female, and 46% (n=101) of those in work had certified time-off for sciatica. Mean pain intensity was 7.2 (2.0) and 6.2 (2.7) for leg and back pain respectively and mean disability (ODI) was 46.5 (18). 60% (n=210) had leg pain for &gt;6 months. Average confidence at baseline (0 to 10) that the ESI would help symptoms was 5.7 (2.4).Of 217 patients reaching 6-week follow-up, mean leg and back pain intensity is 5.0 (2.8) and 4.9 (2.9) respectively and ODI 36.6 (20.4), with 57% reporting improvement (completely recovered/much better/better). Follow-up data collection at 6, 12 and 24-weeks post-ESI is ongoing.ConclusionInterim analysis shows only just over half of patients are reporting improvement at 6 weeks post ESI. The POiSE cohort study will help better identify the patients with sciatica who are most likely to benefit from this treatment.Conflicts of interestNoneSources of fundingThis study is supported by Health Education England and the National Institute for Health and Care Research (HEE/ NIHR ICA Programme Clinical Lectureship, Dr Siobhan Stynes, NIHR300441). The views expressed are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health and Social Care

WILLINGNESS TO RANDOMIZE PATIENTS TO LUMBAR SPINE FUSION SURGERY OR CONSERVATIVE CARE IN THE FORENSIC-UK AND FORENSIC-AUSTRALIA TRIALS

Background and PurposeThe UK's NIHR and Australia's NHMRC have funded two randomised controlled trials (RCTs) to determine if lumbar fusion surgery (LFS) is more effective than best conservative care (BCC) for adults with persistent, severe low back pain (LBP) attributable to lumbar spine degeneration. We aimed to describe clinicians’ decision-making regarding suitability of patient cases for LFS or BCC and level of equipoise to randomise participants in the RCTs.MethodsTwo online cross-sectional surveys distributed via UK and Australian professional networks to clinicians involved in LBP care, collected data on clinical discipline, practice setting and preferred care of five patient cases (ranging in age, pain duration, BMI, imaging findings, neurological signs/symptoms). Clinicians were also asked about willingness to randomise each patient case.ResultsOf 174 responses (73 UK, 101 Australia), 70 were orthopaedic surgeons, 34 neurosurgeons, 65 allied health professionals (AHPs), 5 others. Most worked in public health services only (92% UK, 45% Australia), or a mix of public/private (36% Australia). Most respondents chose BCC as their first-choice management option for all five cases (81–93% UK, 83–91% Australia). For LFS, UK surgeons preferred TLIF (36.4%), whereas Australian surgeons preferred ALIF (54%). Willingness to randomise cases ranged from 37–60% (UK mean 50.7%), and 47–55% (Australian mean 51.9%); orthopaedic and neuro-surgeons were more willing than AHPs.ConclusionWhilst BCC was preferred for all five patient cases, just over half of survey respondents in both the UK and Australia were willing to randomise cases to either LFS or BCC, indicating clinical equipoise (collective uncertainty) needed for RCT recruitment.Conflicts of interestNoneSources of fundingNo specific funding obtained for the surveys. DB, SA, AG and NEF have funding from the National Institute for Health Research (NIHR) UK (FORENSIC-UK NIHR134859); NEF, DB and SA have funding from the Australian National Health and Medical Research Council (NHMRC FORENSIC-Australia GA268233). AG has funding from Orthopaedic Research UK (combined with British Association of Spine Surgeons and British Scoliosis Society) and Innovate UK. NEF is funded through an Australian National Health and Medical Research Council (NHMRC) Investigator Grant (ID: 2018182).

Characteristics and career outcomes of dermatology-focused medical student research grant recipients

Although several dermatology-focused research grants for medical students exist, studies have yet to evaluate the outcomes of grant recipients, such as entry into dermatology residency and academic careers. We have described the characteristics of recipients of dermatology-focused medical student research grants and outcomes, including entry into dermatology residency and academic careers, and we have focused on seven dermatology-focused national and regional research grants eligible for US medical students. Data were obtained from publicly available online sources for grants from 2004 to 2023. Of the 235 medical student recipients of dermatology research grants between 2004 and 2023, 45.5% attended one of the top 20 medical schools funded by National Institutes of Health research grants. Of those who completed medical school, 68.3% advanced to a dermatology residency (n = 123/180). Among board-certified dermatologists, 44.7% held an academic position (n = 34/76); among those who attended a top 20 medical school, 50% held an academic position (n = 23/46) compared with 36.7% who did not (n = 11/30). Limitations of this study include selection bias and incomplete data availability. Medical student research grants allow students to thoughtfully engage in dermatology research early in medical education. These grants may facilitate entry into dermatology residency and academic careers and lead to continued research endeavors.

Comparison of the efficacy and safety of vertebroplasty with different pedicle approaches for osteoporotic vertebral.

To compare the efficacy and safety of vertebroplasty through different pedicle approaches in the treatment of osteoporotic vertebral compression fracture osteoporotic vertebral compression fractures (OVCF) by network meta-analysis. Pubmed, Embase, Cochrane Library, Web of Science. Database for literature retrieval, retrieval time from the establishment of the database to April 2023, the randomized controlled trials of unilateral vertebroplasty (UVP), bilateral vertebroplasty (BVP), unilateral kyphoplasty (UKP), bilateral kyphoplasty (BKP), curved vertebroplasty (CVP) and curved kyphoplasty (CKP) were screened, evaluated and the data were extracted and included in the analysis. STATA 15.0 and ReMan 5.3 were used for data analysis. This study was registered in the National Institute for Health Research (NIHR) with the registration number CRD42023405181. This study included 16 articles with a total of 1712 patients. The order of visual analogue scale (VAS) improvement from good to bad is CVP > BVP > UVP > CKP > BKP > UKP. The order of kyphotic angles improvement from good to bad is CKP > UKP > UKP > UVP > BVP > CVP. The order of bone cement injection from less to more is UVP > CVP > UKP > CKP > BVP > BKP. The order of bone cement leakage rate from less to more is CKP > CVP > UKP > BKP > UVP > BVP. The order of X-ray exposure time from less to more is CKP > CVP > UVP > BVP > UKP > BKP. The order of operation time from less to more is CVP > UVP > UKP > CKP > BVP > BKP. For patients with kyphotic angles, kyphoplasty has unique advantages in improving kyphotic angles. But generally speaking, curved approach can optimize the distribution of bone cement through unilateral approach to achieve the orthopedic effect of bilateral approach, which is a minimally invasive technique with better curative effect and higher safety in the treatment of OVCF.

The development of a set of key points to aid clinicians and researchers in designing and conducting n-of-1 trials

Introductionn-of-1 trials are undertaken to optimise the evaluation of health technologies in individual patients. They involve a single patient receiving treatments, both interventional and control, consecutively over set periods of time, the order of which is decided at random. Although n-of-1 trials are undertaken in medical research it could be argued they have the utility to be undertaken more frequently. We undertook the National Institute for Health Research (NIHR) commissioned DIAMOND (Development of generalisable methodology for n-of-1 trials delivery for very low volume treatments) project to develop key points to assist clinicians and researchers in designing and conducting n-of-1 trials.MethodsThe key points were developed by undertaking a stakeholder workshop, followed by a discussion within the study team and then a stakeholder dissemination and feedback event. The stakeholder workshop sought to gain the perspectives of a variety of stakeholders (including clinicians, researchers and patient representatives) on the design and use of n-of-1 trials. A discussion between the study team was held to reflect on the workshop and draft the key points. Lastly, the stakeholders from the workshop were invited to a dissemination and feedback session where the proposed key points were presented and their feedback gained.ResultsA set of 22 key points were developed based on the insights from the workshop and subsequent discussions. They provide guidance on when an n-of-1 trial might be a viable or appropriate study design and discuss key decisions involved in the design of n-of-1 trials, including determining an appropriate number of treatment periods and cycles, the choice of comparator, recommended approaches to randomisation and blinding, the use of washout periods and approaches to analysis.ConclusionsThe key points developed in the project will support clinical researchers to understand key considerations when designing n-of-1 trials. It is hoped they will support the wider implementation of the study design.

Systematic review and narrative synthesis of the experiences of individuals with chronic pain participating in digital pain management interventions.

The use of digital pain management interventions has grown since the Covid 19 pandemic. The aim of this study was to systematically review and synthesise evidence from qualitative studies regarding the experiences of individuals with chronic pain participating in digital pain management interventions in primary care and community settings. Fourteen databases were searched, as well as citation tracking and hand-searching reference lists of included articles. The latest search was completed by 07/07/2023. Qualitative studies of patient and carer perspectives of digital pain management interventions for adults aged 18 and over with non-malignant chronic pain were included. All studies were appraised for quality using the Critical Appraisal Skills Programme Qualitative Checklist. A narrative synthesis approach was used to synthesise the findings. Normalisation Process Theory was used to understand how individuals with chronic pain make sense of digital pain management interventions and incorporate knowledge, skills and strategies learnt into their day-to-day lives. Eleven studies, encompassing both digital applications for use on smartphones/ mobile devices and user-directed online modular programmes, were included in the synthesis. Three main themes and related subthemes were identified from the included studies: 1) Making sense of the digital intervention (Subthemes: Tailoring to user's needs; Human contact and support; Accessibility of the digital intervention; Personal and environmental factors affecting engagement with digital interventions); 2) Initiating and Maintaining Behaviour Change (Subthemes: Planning activity; Being active); and 3) Personal Growth (Subthemes: Gaining understanding and skills; Gaining and acting on feedback; Negotiating a new relationship with pain). Recommendations. The key recommendations from our findings are that digital pain management interventions should provide: Specific and tailored information for individual participants.Focus on changing attitudes and behaviours and reframing perceptions of pain.Structured goal setting with prompts to review goals.Potential healthcare professional support alongside the digital intervention.Limitations of the review. To reduce bias, it would have been preferable for more than one author to independently fully analyse each paper and to identify themes and sub-themes. Instead, the identified themes and sub-themes were discussed with two other authors in the team (ES, LW) to reach a consensus view on final themes and sub-themes. One author (JS) received a Research Internship and Research Initiation Award funded by NIHR Applied Research Collaboration (ARC) Wessex (https://www.arc-wx.nihr.ac.uk/) and NHS England (https://www.england.nhs.uk/). The protocol for this review was registered with the National Institute of Health Research (NIHR) PROSPERO international database for registering systematic reviews (PROSPERO Registration Number CRD42021257768).

Prognostic significance of troponin in patients with malignancy (NIHR Health Informatics Collaborative TROP-MALIGNANCY study)

BackgroundCardiac troponin is commonly raised in patients presenting with malignancy. The prognostic significance of raised troponin in these patients is unclear.ObjectivesWe sought to investigate the relation between troponin and mortality in a large, well characterised cohort of patients with a routinely measured troponin and a primary diagnosis of malignancy.MethodsWe used the National Institute for Health Research (NIHR) Health Informatics Collaborative data of 5571 patients, who had troponin levels measured at 5 UK cardiac centres between 2010 and 2017 and had a primary diagnosis of malignancy. Patients were classified into solid tumour or haematological malignancy subgroups. Peak troponin levels were standardised as a multiple of each laboratory’s 99th -percentile upper limit of normal (xULN).Results4649 patients were diagnosed with solid tumours and 922 patients with haematological malignancies. Raised troponin was an independent predictor of mortality in all patients (Troponin > 10 vs. <1 adjusted HR 2.01, 95% CI 1.73 to 2.34), in solid tumours (HR 1.84, 95% CI 1.55 to 2.19), and in haematological malignancy (HR 2.72, 95% CI 1.99 to 3.72). There was a significant trend in increasing mortality risk across troponin categories in all three subgroups (p < 0.001).ConclusionRaised troponin level is associated with increased mortality in patients with a primary diagnosis of malignancy regardless of cancer subtype. Mortality risk is stable for patients with a troponin level below the ULN but increases as troponin level increases above the ULN in the absence of acute coronary syndrome.

Prevalence of all epilepsies in urban informal settlements in Nairobi, Kenya: a two-stage population-based study

WHO estimates that more than 50 million people worldwide have epilepsy and 80% of cases are in low-income and middle-income countries. Most studies in Africa have focused on active convulsive epilepsy in rural areas, but there are few data in urban settings. We aimed to estimate the prevalence and spatial distribution of all epilepsies in two urban informal settlements in Nairobi, Kenya. We did a two-stage population-based cross-sectional study of residents in a demographic surveillance system covering two informal settlements in Nairobi, Kenya (Korogocho and Viwandani). Stage 1 screened all household members using a validated epilepsy screening questionnaire to detect possible cases. In stage 2, those identified with possible seizures and a proportion of those screening negative were invited to local clinics for clinical and neurological assessments by a neurologist. Seizures were classified following the International League Against Epilepsy recommendations. We adjusted for attrition between the two stages using multiple imputations and for sensitivity by dividing estimates by the sensitivity value of the screening tool. Complementary log-log regression was used to assess prevalence differences by participant socio-demographics. A total of 56 425 individuals were screened during stage 1 (between Sept 17 and Dec 23, 2021) during which 1126 were classified as potential epilepsy cases. A total of 873 were assessed by a neurologist in stage 2 (between April 12 and Aug 6, 2022) during which 528 were confirmed as epilepsy cases. 253 potential cases were not assessed by a neurologist due to attrition. 30 179 (53·5%) of the 56 425 individuals were male and 26 246 (46·5%) were female. The median age was 24 years (IQR 11-35). Attrition-adjusted and sensitivity-adjusted prevalence for all types of epilepsy was 11·9 cases per 1000 people (95% CI 11·0-12·8), convulsive epilepsy was 8·7 cases per 1000 people (8·0-9·6), and non-convulsive epilepsy was 3·2 cases per 1000 people (2·7-3·7). Overall prevalence was highest among separated or divorced individuals at 20·3 cases per 1000 people (95% CI 15·9-24·7), unemployed people at 18·8 cases per 1000 people (16·2-21·4), those with no formal education at 18·5 cases per 1000 people (16·3-20·7), and adolescents aged 13-18 years at 15·2 cases per 1000 people (12·0-18·5). The epilepsy diagnostic gap was 80%. Epilepsy is common in urban informal settlements of Nairobi, with large diagnostic gaps. Targeted interventions are needed to increase early epilepsy detection, particularly among vulnerable groups, to enable prompt treatment and prevention of adverse social consequences. National Institute for Health Research using Official Development Assistance.

Experiences of Self-Sampling and Future Screening Preferences in Non-Attenders Who Returned an HPV Vaginal Self-Sample in the YouScreen Study: Findings From a Cross-Sectional Questionnaire.

We assessed experiences of human papillomavirus (HPV) vaginal self-sampling and future screening preferences in an ethnically and socio-economically diverse group of women overdue for cervical screening. A postal questionnaire was embedded in the YouScreen self-sampling trial in England: 32.5% (2712/8338) of kit completers returned the survey. Kit non-completers were encouraged to return a questionnaire, but no responses were received. Participants were ethnically diverse (40.3% came from ethnic minority backgrounds), and 59.1% came from the two most deprived quintiles. Differences in confidence in kit completion, trust in the test results and intention to attend a follow-up test if HPV-positive were evaluated using Pearson's χ2 analyses. Binary logistic regression models explored predictors of a future screening choice and preferences for urine versus vaginal self-sampling. Most kit-completers reported high confidence in self-sampling (82.6%) and high trust in the results (79.9%), but experiences varied by ethnicity and screening status. Most free-text comments were positive but some reported difficulties using the device, pain or discomfort. Most women would opt for self-sampling in the future (71.3% vs. 10.4% for a clinician-taken test) and it was more often preferred by ethnic minority groups, overdue screeners and never attenders. Urine self-tests were preferred to vaginal tests (41.9% vs. 15.4%), especially among women from Asian, Black or Other Ethnic backgrounds. Kit-completers were confident, found the test easy to complete, and trusted the self-sample results. However, experiences varied by ethnic group and some women highlighted difficulties with the kit. Most women would prefer self-sampling in the future, but it was not a universal preference, so offering a choice will be important. We did not have direct patient and public involvement and engagement (PPIE) in the questionnaire design. However, patients and public representatives did input into the design of the YouScreen trial and reviewed the wider study materials (e.g. participant information sheet). This questionnaire study was embedded in the YouScreen trial. The protocol for the YouScreen trial is available at https://www.isrctn.com/ISRCTN12759467. The National Institute for Health Research 43 Clinical Research Network (NIHR CRN) Central Portfolio Management System (CPMS) ID is 4441934.

Accuracy and safety of an autonomous artificial intelligence clinical assistant conducting telemedicine follow-up assessment for cataract surgery

Artificial intelligence deployed to triage patients post-cataract surgery could help to identify and prioritise individuals who need clinical input and to expand clinical capacity. This study investigated the accuracy and safety of an autonomous telemedicine call (Dora, version R1) in detecting cataract surgery patients who need further management and compared its performance against ophthalmic specialists. 225 participants were recruited from two UK public teaching hospitals after routine cataract surgery between 17 September 2021 and 31 January 2022. Eligible patients received a call from Dora R1 to conduct a follow-up assessment approximately 3 weeks post cataract surgery, which was supervised in real-time by an ophthalmologist. The primary analysis compared decisions made independently by Dora R1 and the supervising ophthalmologist about the clinical significance of five symptoms and whether the patient required further review. Secondary analyses used mixed methods to examine Dora R1's usability and acceptability and to assess cost impact compared to standard care. This study is registered with ClinicalTrials.gov (NCT05213390) and ISRCTN (16038063). 202 patients were included in the analysis, with data collection completed on 23 March 2022. Dora R1 demonstrated an overall outcome sensitivity of 94% and specificity of 86% and showed moderate to strong agreement (kappa: 0.758-0.970) with clinicians in all parameters. Safety was validated by assessing subsequent outcomes: 11 of the 117 patients (9%) recommended for discharge by Dora R1 had unexpected management changes, but all were also recommended for discharge by the supervising clinician. Four patients were recommended for discharge by Dora R1 but not the clinician; none required further review on callback. Acceptability, from interviews with 20participants, was generally good in routine circumstances but patients were concerned about the lack of a 'human element' in cases with complications. Feasibility was demonstrated by the high proportion of calls completed autonomously (195/202, 96.5%). Staff cost benefits for Dora R1 compared to standard care were £35.18 per patient. The composite of mixed methods analysis provides preliminary evidence for the safety, acceptability, feasibility, and cost benefits for clinical adoption of an artificial intelligence conversational agent, Dora R1, to conduct follow-up assessment post-cataract surgery. Further evaluation in real-world implementation should be conducted to provide additional evidence around safety and effectiveness in a larger sample from a more diverse set of Trusts. This manuscript is independent research funded by the National Institute for Health Research and NHSX (Artificial Intelligence in Health and Care Award, AI_AWARD01852).

A prognostic model for use before elective surgery to estimate the risk of postoperative pulmonary complications (GSU-Pulmonary Score): a development and validation study in three international cohorts

Pulmonary complications are the most common cause of death after surgery. This study aimed to derive and externally validate a novel prognostic model that can be used before elective surgery to estimate the risk of postoperative pulmonary complications and to support resource allocation and prioritisation during pandemic recovery. Data from an international, prospective cohort study were used to develop a novel prognostic risk model for pulmonary complications after elective surgery in adult patients (aged ≥18 years) across all operation and disease types. The primary outcome measure was postoperative pulmonary complications at 30 days after surgery, which was a composite of pneumonia, acute respiratory distress syndrome, and unexpected mechanical ventilation. Model development with candidate predictor variables was done in the GlobalSurg-CovidSurg Week dataset (global; October, 2020). Two structured machine learning techniques were explored (XGBoost and the least absolute shrinkage and selection operator [LASSO]), and the model with the best performance (GSU-Pulmonary Score) underwent internal validation using bootstrap resampling. The discrimination and calibration of the score were externally validated in two further prospective cohorts: CovidSurg-Cancer (worldwide; February to August, 2020, during the COVID-19 pandemic) and RECON (UK and Australasia; January to October, 2019, before the COVID-19 pandemic). The model was deployed as an online web application. The GlobalSurg-CovidSurg Week and CovidSurg-Cancer studies were registered with ClinicalTrials.gov, NCT04509986 and NCT04384926. Prognostic models were developed from 13 candidate predictor variables in data from 86 231 patients (1158 hospitals in 114 countries). External validation included 30 492 patients from CovidSurg-Cancer (726 hospitals in 75 countries) and 6789 from RECON (150 hospitals in three countries). The overall rates of pulmonary complications were 2·0% in derivation data, and 3·9% (CovidSurg-Cancer) and 4·7% (RECON) in the validation datasets. Penalised regression using LASSO had similar discrimination to XGBoost (area under the receiver operating curve [AUROC] 0·786, 95% CI 0·774-0·798 vs 0·785, 0·772-0·797), was more explainable, and required fewer covariables. The final GSU-Pulmonary Score included ten predictor variables and showed good discrimination and calibration upon internal validation (AUROC 0·773, 95% CI 0·751-0·795; Brier score 0·020, calibration in the large [CITL] 0·034, slope 0·954). The model performance was acceptable on external validation in CovidSurg-Cancer (AUROC 0·746, 95% CI 0·733-0·760; Brier score 0·036, CITL 0·109, slope 1·056), but with some miscalibration in RECON data (AUROC 0·716, 95% CI 0·689-0·744; Brier score 0·045, CITL 1·040, slope 1·009). This novel prognostic risk score uses simple predictor variables available at the time of a decision for elective surgery that can accurately stratify patients' risk of postoperative pulmonary complications, including during SARS-CoV-2 outbreaks. It could inform surgical consent, resource allocation, and hospital-level prioritisation as elective surgery is upscaled to address global backlogs. National Institute for Health Research.