National Institute For Health Research Research Articles

Peter Goadsby: knowledge of politics, politics of knowledge

If you work in headache and migraine, you don't need me to tell who Peter Goadsby is, but just in case, he is professor of neurology and director of the National Institute for Health Research's clinical research facility at King's College London, consultant neurologist at King's College Hospital and Great Ormond Street Hospital (both London, UK), and professor emeritus of neurology at the University of California (Los Angeles, CA, USA). I am sure you'll know that he challenged the received vascular mechanism of migraine to unravel one based on dysfunctional neuropeptide production in the trigeminal nerve. You will also know his work lies behind the advent of drugs targeting calcitonin gene-related peptide (CGRP) and its receptor—monoclonal antibodies for keeping migraine at bay, and gepants, which have given relief to many migraineurs. You might even know about his being co-recipient of the 2021 Brain Prize, and his election as a fellow to the Royal Society in May, 2022. But you won't be aware that he initially told me he was so focused on his work that he'd be pretty dull to write about. Well, that was hardly true: especially when he told me he once thought he'd become a politician—a politician with knowledge.

Conservative management versus tonsillectomy in adults with recurrent acute tonsillitis in the UK (NATTINA): a multicentre, open-label, randomised controlled trial

Tonsillectomy is regularly performed in adults with acute tonsillitis, but with scarce evidence. A reduction in tonsillectomies has coincided with an increase in acute adult hospitalisation for tonsillitis complications. We aimed to assess the clinical effectiveness and cost-effectiveness of conservative management versus tonsillectomy in patients with recurrent acute tonsillitis. This pragmatic multicentre, open-label, randomised controlled trial was conducted in 27 hospitals in the UK. Participants were adults aged 16 years or older who were newly referred to secondary care otolaryngology clinics with recurrent acute tonsillitis. Patients were randomly assigned (1:1) to receive tonsillectomy or conservative management using random permuted blocks of variable length. Stratification by recruiting centre and baseline symptom severity was assessed using the Tonsil Outcome Inventory-14 score (categories defined as mild 0-35, moderate 36-48, or severe 49-70). Participants in the tonsillectomy group received elective surgery to dissect the palatine tonsils within 8 weeks after random assignment and those in the conservative management group received standard non-surgical care during 24 months. The primary outcome was the number of sore throat days collected during 24 months after random assignment, reported once per week with a text message. The primary analysis was done in the intention-to-treat (ITT) population. This study is registered with the ISRCTN registry, 55284102. Between May 11, 2015, and April 30, 2018, 4165 participants with recurrent acute tonsillitis were assessed for eligibility and 3712 were excluded. 453 eligible participants were randomly assigned (233 in the immediate tonsillectomy group vs 220 in the conservative management group). 429 (95%) patients were included in the primary ITT analysis (224 vs 205). The median age of participants was 23 years (IQR 19-30), with 355 (78%) females and 97 (21%) males. Most participants were White (407 [90%]). Participants in the immediate tonsillectomy group had fewer days of sore throat during 24 months than those in the conservative management group (median 23 days [IQR 11-46] vs 30 days [14-65]). After adjustment for site and baseline severity, the incident rate ratio of total sore throat days in the immediate tonsillectomy group (n=224) compared with the conservative management group (n=205) was 0·53 (95% CI 0·43 to 0·65; <0·0001). 191 adverse events in 90 (39%) of 231 participants were deemed related to tonsillectomy. The most common adverse event was bleeding (54 events in 44 [19%] participants). No deaths occurred during the study. Compared with conservative management, immediate tonsillectomy is clinically effective and cost-effective in adults with recurrent acute tonsillitis. National Institute for Health Research.

The global impact of tobacco control policies on smokeless tobacco use: a systematic review

Smokeless tobacco, used by more than 300 million people globally, results in substantial morbidity and mortality. For smokeless tobacco control, many countries have adopted policies beyond the WHO Framework Convention on Tobacco Control, which has been instrumental in reducing smoking prevalence. The impact of these policies (within and outside the Framework Convention on Tobacco Control) on smokeless tobacco use remains unclear. We aimed to systematically review policies that are relevant to smokeless tobacco and its context and investigate their impact on smokeless tobacco use. In this systematic review, we searched 11 electronic databases and grey literature between Jan 1, 2005, and Sept 20, 2021, in English and key south Asian languages, to summarise smokeless tobacco policies and their impact. Inclusion criteria were all types of studies on smokeless tobacco users that mentioned any smokeless tobacco relevant policies since 2005, except systematic reviews. Policies issued by organisations or private institutions were excluded as well as studies on e-cigarettes and Electronic Nicotine Delivery System except where harm reduction or switching were evaluated as a tobacco cessation strategy. Two reviewers independently screened articles, and data were extracted after standardisation. Quality of studies was appraised using the Effective Public Health Practice Project's Quality Assessment Tool. Outcomes for impact assessment included smokeless tobacco prevalence, uptake, cessation, and health effects. Due to substantial heterogeneity in the descriptions of policies and outcomes, data were descriptively and narratively synthesised. This systematic review was registered in PROSPERO (CRD42020191946). 14 317 records were identified, of which 252 eligible studies were included as describing smokeless tobacco policies. 57 countries had policies targeting smokeless tobacco, of which 17 had policies outside the Framework Convention on Tobacco Control for smokeless tobacco (eg, spitting bans). 18 studies evaluated the impact, which were of variable quality (six strong, seven moderate, and five weak) and reported mainly on prevalence of smokeless tobacco use. The body of work evaluating policy initiatives based on the Framework Convention on Tobacco Control found that these initiatives were associated with reductions in smokeless tobacco prevalence of between 4·4% and 30·3% for taxation and 22·2% and 70·9% for multifaceted policies. Two studies evaluating the non-Framework policy of sales bans reported significant reductions in smokeless tobacco sale (6·4%) and use (combined sex 17·6%); one study, however, reported an increased trend in smokeless tobacco use in the youth after a total sales ban, likely due to cross-border smuggling. The one study reporting on cessation found a 13·3% increase in quit attempts in individuals exposed (47·5%) to Framework Convention on Tobacco Control policy: education, communication, training, and public awareness, compared with non-exposed (34·2%). Many countries have implemented smokeless tobacco control policies, including those that extend beyond the Framework Convention on Tobacco Control. The available evidence suggests that taxation and multifaceted policy initiatives are associated with meaningful reductions in smokeless tobacco use. UK National Institute for Health Research.

Profiling post-COVID-19 condition across different variants of SARS-CoV-2: a prospective longitudinal study in unvaccinated wild-type, unvaccinated alpha-variant, and vaccinated delta-variant populations

Self-reported symptom studies rapidly increased understanding of SARS-CoV-2 during the COVID-19 pandemic and enabled monitoring of long-term effects of COVID-19 outside hospital settings. Post-COVID-19 condition presents as heterogeneous profiles, which need characterisation to enable personalised patient care. We aimed to describe post-COVID-19 condition profiles by viral variant and vaccination status. In this prospective longitudinal cohort study, we analysed data from UK-based adults (aged 18-100 years) who regularly provided health reports via the Covid Symptom Study smartphone app between March 24, 2020, and Dec 8, 2021. We included participants who reported feeling physically normal for at least 30 days before testing positive for SARS-CoV-2 who subsequently developed long COVID (ie, symptoms lasting longer than 28 days from the date of the initial positive test). We separately defined post-COVID-19 condition as symptoms that persisted for at least 84 days after the initial positive test. We did unsupervised clustering analysis of time-series data to identify distinct symptom profiles for vaccinated and unvaccinated people with post-COVID-19 condition after infection with the wild-type, alpha (B.1.1.7), or delta (B.1.617.2 and AY.x) variants of SARS-CoV-2. Clusters were then characterised on the basis of symptom prevalence, duration, demography, and previous comorbidities. We also used an additional testing sample with additional data from the Covid Symptom Study Biobank (collected between October, 2020, and April, 2021) to investigate the effects of the identified symptom clusters of post-COVID-19 condition on the lives of affected people. We included 9804 people from the COVID Symptom Study with long COVID, 1513 (15%) of whom developed post-COVID-19 condition. Sample sizes were sufficient only for analyses of the unvaccinated wild-type, unvaccinated alpha variant, and vaccinated delta variant groups. We identified distinct profiles of symptoms for post-COVID-19 condition within and across variants: four endotypes were identified for infections due to the wild-type variant (in unvaccinated people), seven for the alpha variant (in unvaccinated people), and five for the delta variant (in vaccinated people). Across all variants, we identified a cardiorespiratory cluster of symptoms, a central neurological cluster, and a multi-organ systemic inflammatory cluster. These three main clusers were confirmed in a testing sample. Gastrointestinal symptoms clustered in no more than two specific phenotypes per viral variant. Our unsupervised analysis identified different profiles of post-COVID-19 condition, characterised by differing symptom combinations, durations, and functional outcomes. Our classification could be useful for understanding the distinct mechanisms of post-COVID-19 condition, as well as for identification of subgroups of individuals who might be at risk of prolonged debilitation. UK Government Department of Health and Social Care, Chronic Disease Research Foundation, The Wellcome Trust, UK Engineering and Physical Sciences Research Council, UK Research and Innovation London Medical Imaging & Artificial Intelligence Centre for Value-Based Healthcare, UK National Institute for Health Research, UK Medical Research Council, British Heart Foundation, UK Alzheimer's Society, and ZOE.

Utilizing Neurodiverse Workplace Strategies to Support the Growing Population of Long COVID Cases in a Neuro inclusive Workplace: A Paradigm Shift for Neuro acquired Employees

The COVID-19 pandemic has led to the emergence of long COVID, a condition in which patients report persistent symptoms after recovering from acute SARS-CoV-2 infection. A review conducted by the National Institute for Health Research (NIHR) suggests that long COVID may actually consist of four different syndromes: post-intensive care syndrome, post-viral fatigue syndrome, and long-term COVID syndrome. The absence of a clear definition for this condition may lead to under-recognition and under-treatment of the symptoms experienced by those affected. Moreover, existing programs designed for neurodiverse individuals may be adapted to support the growing neuroacquired population. Communication strategies, such as providing processing time and visual aids, can be useful in workplace settings. Additionally, offering group communication assistance and using plain language and visual signposts can help minimize stress and increase understanding. Providing clear agendas, specific instructions, and feedback that is both direct and positive can also help individuals with long COVID to adjust and perform better in the workplace. Finally, taking into account communication preferences and the availability of virtual communication platforms can help alleviate anxiety for neurodiverse individuals. Understanding the nuances of long COVID and its impact on individuals and the workplace can help healthcare providers and employers provide the support and accommodations necessary for this growing population.

Patient and public co-creation of healthcare safety and healthcare system resilience: The case of COVID-19.

Healthcare system resilience is a conceptual approach that seeks to explore how health services adapt and respond to variability in demand and resources. As has been witnessed since the beginning of the COVID-19 pandemic, healthcare services have undergone many reconfigurations. One understudied aspect of how the 'system' is able to adapt and respond is the contribution of key stakeholders-patients and families, and in the context of the pandemic, the general public as a whole. This study aimed to understand what people were doing during the first wave of the pandemic to protect the safety of their health, and the health of others from COVID-19, and the resilience of the healthcare system. Social media (Twitter) was used as a method of recruitment due to its ability for social reach. Twenty-one participants took part in 57 semistructured interviews over three time points from June to September 2020. The included an initial interview and invitation to two follow-up interviews after 3 and 6 weeks. Interviews were conducted virtually using Zoom-an encrypted secure video conferencing software. A reflexive thematic analysis approach to analysis was used. Three themes, each with its own subthemes were identified in the analysis: (1) A 'new safety normal'; (2) Existing vulnerabilities and heightened safetyand (3) Are we all in this together? This study found that the public had a role in supporting the resilience of healthcare services and systems during the first wave of the pandemic by adapting their behaviour to protect themselves and others, and to avoid overwhelming the National Health Service. People who had existing vulnerabilities were more likely to experience safety gaps in their care, and be required to step in to support their safety, despite it being more difficult for them to do so. It may be that the most vulnerable were previously required to do this extra work to support the safety of their care and that the pandemic has just illuminated this issue. Future research should explore existing vulnerabilities and inequalities, and the heightened safety consequences created by the pandemic. The National Institute for Health Research (NIHR) Yorkshire and Humber Patient Safety Translational Research Centre (NIHR Yorkshire and Humber PSTRC), Patient and Public Involvement and EngagementResearch Fellowand NIHR Yorkshire and Humber PSTRC Patient Involvement in Patient Safety theme lay leader are involved in the preparation of a lay version of the findings within this manuscript.

CycLing and EducATion (CLEAT): protocol for a single centre randomised controlled trial of a cycling and education intervention versus standard physiotherapy care for the treatment of hip osteoarthritis

BackgroundOsteoarthritis (OA) is a chronic degenerative joint disorder for which there is no known cure. Non-surgical management for people with mild-to-moderate hip OA focuses mainly on alleviating pain and maximising function via the National Institute for Health and Care Excellence (NICE) recommended combination of education and advice, exercise, and, where appropriate, weight loss. The CHAIN (Cycling against Hip pAIN) intervention is a group cycling and education intervention conceived as a way of implementing the NICE guidance.MethodsCycLing and EducATion (CLEAT) is a pragmatic, two parallel arm, randomised controlled trial comparing CHAIN with standard physiotherapy care for the treatment of mild-to-moderate hip OA. We will recruit 256 participants referred to the local NHS physiotherapy department over a 24-month recruitment period. Participants diagnosed with hip OA according to NICE guidance and meeting the criteria for GP exercise referral will be eligible to participate. Primary outcome is the difference in Hip Disability and Osteoarthritis Outcome Score (HOOS) function, daily living subscale between those receiving CHAIN and standard physiotherapy care. Secondary outcomes include performance-based functional measures (40 m walking, 30s chair stand and stair climb tests), ability for patient to self-care (patient activation measure) and self-reported health-related resource use including primary and secondary care contacts. The primary economic endpoint is the number of quality adjusted life years (QALYs) at 24 weeks follow-up. The study is funded by the National Institute for Health Research, Research for Patient Benefit PB-PG-0816-20033.DiscussionThe literature identifies a lack of high-quality trials which inform on the content and design of education and exercise in the treatment of patients with hip OA and explore cost-effectiveness. CLEAT is a pragmatic trial which seeks to build further evidence of the clinical benefits of the CHAIN intervention compared to standard physiotherapy care within a randomised, controlled trial setting, and examine its cost-effectiveness.Trial registration numberISRCTN19778222. Protocol v4.1, 24th October 2022.

Stressful life events and relapse of psychosis: analysis of causal association in a 2-year prospective observational cohort of individuals with first-episode psychosis in the UK

Despite accumulating evidence of an association between stressful life events and psychosis relapse, the extent to which this is a causal relationship remains unclear. We aimed to examine the association between exposure to, and number of, stressful life events after initial psychosis onset and psychosis relapse. In this 2-year prospective observational study, we recruited individuals with first-episode psychosis, aged 18-65 years, who presented to psychiatric services in south London, UK. Participants were assessed via interview, with additional data obtained from electronic clinical records. Stressful life events were recorded at psychosis onset and during the 2-year follow-up using a brief questionnaire that assesses 12 major life events. Psychosis relapse was defined as inpatient admission because of symptom exacerbation within 2 years from psychosis onset. We examined the time to first psychosis relapse and the number and length of relapses using survival and binomial regression analyses. We used fixed-effects regression and cross-lagged path analysis to examine the directionality of effects and control for unmeasured confounders. Between April 12, 2002, and July 26, 2013, 256 individuals with first-episode psychosis (100 [39%] female and 156 [61%] male; 16 [6%] Asian, 140 [55%] Black African or Caribbean, 86 [34%] White, and 14 [6%] mixed ethnicity) were recruited, with a mean age of onset of psychosis of 28·06 years (SD 8·03; range 17·21-56·03). 93 (36%) participants experienced at least one relapse during the 2-year follow-up. 253 individuals had all relevant data and were included in analyses. For people exposed to stressful life events after the onset of psychosis, the adjusted hazard (hazard ratio [HR] 2·60, 95% CI 1·63-4·16, p<0·0001), incidence (incidence rate ratio [IRR] 1·87, 1·24-2·80, p=0·0026), and length (IRR 2·53, 1·40-4·67, p=0·0011) of relapse were greater than for those who were unexposed. These relationships were dose dependent (HR 1·36; 1·09-1·69, p=0·0054; incidence IRR 1·26, 1·02-1·53, p=0·023; length IRR 1·52, 1·12-2·12, p=0·0028). Adjusted fixed-effects models showed a higher (odds ratio [OR] 3·82, 1·82-8·00, p=0·0004) and dose-dependent (OR 1·62, 1·18-2·21, p=0·0028) risk of relapse when stressful life events preceded relapse compared with the period when they did not. Cross-lagged path analysis confirmed an effect of stressful life events on the number of subsequent relapses (β=0·66, p=0·0055) that was dose dependent (β=0·29, p=0·029), but it did not show an effect of relapses on subsequent risk or number of stressful life events. These results provide converging evidence of a causal effect of stressful life events on the risk of relapse in psychosis. They suggest that there is a need to develop interventions at the individual and health-service level that could mitigate the harmful effects of stressful life events. National Institute for Health Research, UK.

Anti-science conspiracies pose new threats to US biomedicine in 2023.

Anti-science conspiracies pose new threats to US biomedicine in 2023.

COVID-19 vaccination decisions among Gypsy, Roma, and Traveller communities: A qualitative study moving beyond “vaccine hesitancy”

BackgroundMany people refuse vaccination and it is important to understand why. Here we explore the experiences of individuals from Gypsy, Roma, and Traveller groups in England to understand how and why they decided to take up or to avoid COVID-19 vaccinations. MethodsWe used a participatory, qualitative design, including wide consultations, in-depth interviews with 45 individuals from Gypsy, Roma, and Traveller, communities (32 female, 13 male), dialogue sessions, and observations, in five locations across England between October 2021 and February 2022. FindingsVaccination decisions overall were affected by distrust of health services and government, which stemmed from prior discrimination and barriers to healthcare which persisted or worsened during the pandemic. We found the situation was not adequately characterised by the standard concept of “vaccine hesitancy”. Most participants had received at least one COVID-19 vaccine dose, usually motivated by concerns for their own and others’ health. However, many participants felt coerced into vaccination by medical professionals, employers, and government messaging. Some worried about vaccine safety, for example possible impacts on fertility. Their concerns were inadequately addressed or even dismissed by healthcare staff. InterpretationA standard "vaccine hesitancy" model is of limited use in understanding vaccine uptake in these populations, where authorities and health services have been experienced as untrustworthy in the past (with little improvement during the pandemic). Providing more information may improve vaccine uptake somewhat; however, improved trustworthiness of health services for GRT communities is essential to increase vaccine coverage. FundingThis paper reports on independent research commissioned and funded by the National Institute for Health Research (NIHR) Policy Research Programme. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR, the Department of Health and Social Care or its arm's length bodies, and other Government Departments.

Computerised cognitive assessment in patients with traumatic brain injury: an observational study of feasibility and sensitivity relative to established clinical scales.

Online technology could potentially revolutionise how patients are cognitively assessed and monitored. However, it remains unclear whether assessments conducted remotely can match established pen-and-paper neuropsychological tests in terms of sensitivity and specificity. This observational study aimed to optimise an online cognitive assessment for use in traumatic brain injury (TBI) clinics. The tertiary referral clinic in which this tool has been clinically implemented typically sees patients a minimum of 6 months post-injury in the chronic phase. Between March and August 2019, we conducted a cross-group, cross-device and factor analyses at the St. Mary's Hospital TBI clinic and major trauma wards at Imperial College NHS trust and St. George's Hospital in London (UK), to identify a battery of tasks that assess aspects of cognition affected by TBI. Between September 2019 and February 2020, we evaluated the online battery against standard face-to-face neuropsychological tests at the Imperial College London research centre. Canonical Correlation Analysis (CCA) determined the shared variance between the online battery and standard neuropsychological tests. Finally, between October 2020 and December 2021, the tests were integrated into a framework that automatically generates a results report where patients' performance is compared to a large normative dataset. We piloted this as a practical tool to be used under supervised and unsupervised conditions at the St. Mary's Hospital TBI clinic in London (UK). The online assessment discriminated processing-speed, visual-attention, working-memory, and executive-function deficits in TBI. CCA identified two significant modes indicating shared variance with standard neuropsychological tests (r=0.86, p<0.001 and r=0.81, p=0.02). Sensitivity to cognitive deficits after TBI was evident in the TBI clinic setting under supervised and unsupervised conditions (F (15,555)=3.99; p<0.001). Online cognitive assessment of TBI patients is feasible, sensitive, and efficient. When combined with normative sociodemographic models and autogenerated reports, it has the potential to transform cognitive assessment in the healthcare setting. This work was funded by a National Institute for Health Research (NIHR) Invention for Innovation (i4i) grant awarded to DJS and AH (II-LB-0715-20006).

ASPIRE guidelines and their enlightenment on application of sham acupuncture in clinical researches

Reasonable and standard application of sham acupuncture control is the key to determine the quality of acupuncture clinical trials, and is also a difficult problem faced by acupuncture clinical research. The UK National Institute for Health Research and the Medical Research Council jointly published the Applying Surgical Placebo in Randomised Evaluation (ASPIRE) guidelines on the application of placebo surgical operation in randomized evaluation, which includes 4 parts: rationale and ethics, design, conduct, and interpretation and translation, providing comprehensive guidance for the application of placebo controls in surgical trials. As an operational intervention, acupuncture is similar to surgery, so, ASPIRE guidelines can also provide certain guidance for the application of sham acupuncture. In the present paper, we introduce the ASPIRE guidelines, and put forward its enlightenment and reference to the application of sham acupuncture control in combination with retrospecting the current situations of sham acupuncture research. We hold that future studies should strengthen the consideration of the rationality and ethics of sham acupuncture, standardize the design of sham acupuncture control, and convey the information related to sham acupuncture to patients with appropriate descriptions.

E060 Testing a new prototype osteoporosis shared decision-making intervention in UK Fracture Liaison Services: patient and clinician perspectives of ‘iFraP’

Abstract Background/Aims Shared decision-making (SDM) is a joint process in which a person and healthcare professional work together to reach decisions about care. The Improving uptake of Fracture Prevention drug treatments (iFraP) study developed a prototype theoretically-informed intervention consisting of a computerised decision aid (DA) and Fracture Liaison Service (FLS) clinician training package to improve SDM about osteoporosis medicines. This abstract focuses on the early prototype iFraP in-practice testing phase that explored perceived acceptability of iFraP by those using it, barriers to, and facilitators of, implementation of the prototype iFraP in practice, and necessary changes required ahead of a full-scale randomised controlled trial (RCT). Methods In-practice testing was conducted at one FLS site. Participating FLS clinicians completed the prototype iFraP clinician training package, covering enhanced communication skills (e.g SDM, risk communication and health literacy techniques). Consenting patients with a recent fragility fracture referred for an FLS consultation were eligible to participate. Three cycles of iFraP in-practice testing were completed. Each cycle included observed iFraP consultations and post-consultation patient think-aloud interviews. After each complete cycle, the FLS clinician(s) was interviewed. Data were analysed using a framework approach. The Theoretical Framework of Acceptability and Theoretical Domains Framework facilitated understanding of iFraP acceptability and barriers to, and facilitators of, implementation. Results Four FLS clinicians (3 nurses, 1 allied health professional) completed the iFraP clinician training and delivered 10 iFraP consultations (8 face-to-face, 2 telephone) using the iFraP DA with participating patients (n = 3 cycle 1; n = 3 cycle 2; n = 4 cycle 3). In total, the four FLS clinicians completed 7 interviews, with all 10 patients completing a post-consultation interview. Findings demonstrate that patients and clinicians perceived the prototype iFraP DA as acceptable. Clinicians suggested that the iFraP DA supported them to elicit and address patient perceptions, increase patient involvement, and provide patients with sufficient and accessible information. Patients and clinicians expressed wanting to use iFraP in future FLS appointments, with some clinicians continuing to use the DA outside of iFraP in-practice testing. Identified barriers included: some clinicians questioned both the use of iFraP DA with patients not recommended first-line drug treatment; and, expressed concern that iFraP DA could extend the consultation length. Our findings demonstrated necessary updates to meet user needs and overcome identified barriers to iFraP intervention use, including presentation and structural changes to support integration of the iFraP DA into the consultation flow. Clinicians also provided feedback to improve the training package, including the need to demonstrate the DA in use, and increased allocated time to practice using the DA. Conclusion The iFraP intervention was perceived as acceptable, with the potential to support SDM about osteoporosis medicines. The iFraP RCT will now test our improved iFraP intervention across 3 FLS sites in England. Disclosure L. Bullock: None. N. Tyler: None. M. Thompson: None. S. Ryan: Grants/research support; the General Nursing Council for England and Wales Trust. J. Lefroy: None. S. Leyland: None. J. Fleming: None. E.M. Clark: None. S. Thomas: Other; owns Prescribing Decision Support Ltd that developed the iFraP decision aid. C. Gidlow: None. C.P. Iglesias-Urrutia: None. T.W. O'Neill: Grants/research support; supported by the NIHR Manchester Biomedical Research Centre. C.D. Mallen: Grants/research support; funded by the NIHR Applied Research Collaboration West Midlands, funded by the NIHR School for Primary Care Research. C. Jinks: Grants/research support; part funded by NIHR Applied Research Collaboration (ARC) West Midlands. Z. Paskins: Grants/research support; funded by the National Institute for Health Research (NIHR) [Clinician Scientist Award (CS-2018-18-ST2-010)/NIHR Academy].

P080 Print and online news representations of osteoporosis and its treatment in the UK: a framing analysis

Abstract Background/Aims Osteoporosis is a common condition which weakens bones, meaning bones can break easily. Breaking a bone may be a painful experience with significant physical, psychological, and social impact. Experts have recently proposed the “osteoporosis crisis” meaning those at risk are not being identified and for those who are, treatment uptake remains low. It is unclear what is driving the crisis. One influence may be news media, as news can impact on health beliefs and behaviours. This study aimed to investigate how osteoporosis and its treatment are represented in UK print and online news. Methods First, to explore the amount of newspaper coverage of osteoporosis compared to other long-term conditions (LTCs), a ProQuest search of twelve highly circulated newspapers between the 1st of October 2019 and the 30th of September 2020 was conducted, using the keyword “osteoporosis” and keywords relating to eight other LTCs. Next, the search on articles relating to osteoporosis was extended by using the search function on each newspaper’s website. The articles containing the keyword “osteoporosis” were subject to an inductive framing analysis. Analysis involved identifying dominant frames and components within them including problem definition, causal attribution, moral evaluation, and treatment recommendation. Results From the ProQuest comparison search, fewer articles were published containing the keyword “osteoporosis” (n = 148) compared to any of the other LTCs (“rheumatoid arthritis” (n = 194) to “cancer” (n = 9,644)). A total of 218 articles from ProQuest and online news platforms were identified for the framing analysis. Three dominant frames were present: Biomedical (n = 53 articles), Lifestyle (n = 47 articles) and Human-Interest (n = 118 articles). Osteoporosis was presented as a problem of menopause and ageing across all frames. The cause was attributed to either an imbalance in bone turnover (biomedical), poor diet and inactivity (lifestyle) and often disordered eating and menopause (human-interest). Moral evaluations of osteoporosis included descriptions of osteoporosis as a serious condition (biomedical), women were often described as vulnerable (lifestyle), and people with the condition were described as disabled, elderly and suffering (human-interest). Treatment recommendations highlighted pharmacological treatment (biomedical), or prevention through lifestyle choices (lifestyle). Human-interest stories included celebrity perspectives which were characterised by wealthy, glamorous and royal individuals and events, and lay stories which presented shocking or unusual cases and described those with the condition as victims and sufferers. Conclusion This study found that osteoporosis receives little media attention compared to other LTCs. There was little overlap between biomedical, and lifestyle components which reinforce osteoporosis as either a serious condition requiring medical intervention or as a self-inflicted condition controllable through individual actions. Human-interest stories highlighted pain and suffering of those afflicted. Results will inform focus groups exploring audience perceptions of media about osteoporosis and contribute to recommendations for reporting osteoporosis in the media. Disclosure R. Turner: None. C. Jinks: Grants/research support; CJ is part funded by the NIHR Applied Research Collaboration (ARC) West Midlands. S. Holohan: None. Z. Paskins: Grants/research support; ZP is funded by the National Institute for Health Research (NIHR) (Clinician Scientist Award (CS-2018-18-ST2- 010)/NIHR Academy).

P083 How are beliefs about osteoporosis medicines elicited and addressed in clinical consultations: a video observational study

Abstract Background/Aims In shared decision-making conversations, patients with or at risk of osteoporosis and their clinicians collaborate to decide which drug treatments fit best for each person. The Perceptions and Practicalities Approach (PAPA) specifies three core considerations of drug uptake and commitment: 1) patient’s perceived personal need for treatment (necessity beliefs). 2) patient concerns about the potential adverse consequences of drugs (e.g. side effects). 3) practical difficulties (e.g. limitations in capacity and resources). This study aims to explore how discussions about perceptions and practicalities of osteoporosis drug treatment arise and evolve in the context of clinical consultations about osteoporosis. Methods Secondary analysis of 38 video-recorded primary care consultations from a Mayo Clinic trial evaluating the Osteoporosis Choice Decision Aid. Video-recorded consultations included ‘usual care’ (n = 24) and decision aid (n = 14). Patient participants were aged 50 and over with osteopenia or osteoporosis not already receiving drug treatment. A quantitative coding scheme, informed by the PAPA, was developed to extract: i) how clinicians framed the ‘problem’ of osteoporosis, including: bone density results, fracture risk, physical impact, social impact, or psychological impact of fracture. ii) whether clinicians asked about the patients’ views of osteoporosis, patients own bone health, and the necessity, concerns, or practical issues associated with osteoporosis drugs. iii) whether clinicians personalised discussions about osteoporosis drugs to patients perceived: importance or need, side effects or harms, or practical issues. Two independent study team members dual extracted data, with a third member resolving discrepancies. Extracted data was summarised using descriptive statistics. Results Commonly, clinicians framed osteoporosis using the patient’s bone density results (n = 38,100%) and fracture risk (n = 30,79%). In contrast, few clinicians acknowledged the potential physical impacts of fracture (n = 5,13%), with no clinicians discussing the possible psychological or social impacts. Clinicians asked 24 questions to elicit patient views in 16 of the 38 encounters (42%, range 0-4 questions per consult). The 24 questions concerned patient views about osteoporosis (n = 1,4%), their bone health (n = 5,21%), or the necessity (n = 1,4%), concerns (n = 2,8%), or practical issues associated with osteoporosis drugs (n = 2,8%). Importantly, 14 consultations (37%) contained no questions to elicit patient views. Across the 38 consultations, clinicians personalised information about the patient’s need for osteoporosis drugs in 15 consultations (39%), with less personalisation about the side effects/harms (n = 10,26%), or practical issues (n = 6,16%) associated with osteoporosis drugs. Conclusion Clinical consultations rarely considered key personal determinants of osteoporosis drug uptake and commitment. Even when clinicians used an osteoporosis decision aid, few discussions specifically elicited or addressed patients’ personal treatment necessity beliefs, concerns and practical difficulties. Additionally, clinicians seldom acknowledged the potential physical and psychosocial impacts of osteoporosis. The findings demonstrate the need for multicomponent interventions, incorporating the PAPA-based approach, to facilitate shared decision-making that takes account of patient perceptions and practicalities. Disclosure A.W. Hawarden: Grants/research support; AH is funded by a Versus Arthritis Clinical Doctoral Fellowship (grant reference 227260). L. Bullock: None. M. León-García: Grants/research support; ML-G had financial support from the Spanish Health Institute Carlos III (ISCIII) co-funded by the European Regional Development Fund (Grant number: F18/00014).. S.A. Hartasanchez: None. I. Hargraves: None. R. Horne: None. A. Maraboto: None. M. Kunneman: Grants/research support; MK had financial support from the Dutch Research Council (NWO) and The Netherlands Organisation for Health Research and Development (ZonMw) (#016.196.138). C. Jinks: Grants/research support; CJ is part funded by NIHR Applied Research Collaboration (ARC) West Midlands. Z. Paskins: Grants/research support; ZP is funded by the National Institute for Health Research (NIHR) [Clinician Scientist Award (CS-2018-18-ST2-010)/NIHR Academy].

Lived experience-centred word clouds may improve research uncertainty gathering in priority setting partnerships

IntroductionAO Spine RECODE-DCM was a multi-stakeholder priority setting partnership (PSP) to define the top ten research priorities for degenerative cervical myelopathy (DCM). Priorities were generated and iteratively refined using a series of surveys administered to surgeons, other healthcare professionals (oHCP) and people with DCM (PwDCM). The aim of this work was to utilise word clouds to enable the perspectives of people with the condition to be heard earlier in the PSP process than is traditionally the case. The objective was to evaluate the added value of word clouds in the process of defining research uncertainties in National Institute for Health Research (NIHR) James Lind Alliance (JLA) Priority Setting Partnerships.MethodsPatient-generated word clouds were created for the four survey subsections of the AO Spine RECODE-DCM PSP: diagnosis, treatment, long-term management and other issues. These were then evaluated as a nested methodological study. Word-clouds were created and iteratively refined by an online support group of people with DCM, before being curated by the RECODE-DCM management committee and expert healthcare professional representatives. The final word clouds were embedded within the surveys administered at random to 50% of participants. DCM research uncertainties suggested by participants were compared pre- and post-word cloud presentation.ResultsA total of 215 (50.9%) participants were randomised to the word cloud stream, including 118 (55%) spinal surgeons, 52 (24%) PwDCM and 45 (21%) oHCP. Participants submitted 434 additional uncertainties after word cloud review: word count was lower and more uniform across each survey subsections compared to pre-word cloud uncertainties. Twenty-three (32%) of the final 74 PSP summary questions did not have a post-word cloud contribution and no summary question was formed exclusively on post-word cloud uncertainties. There were differences in mapping of pre- and post-word cloud uncertainties to summary questions, with greater mapping of post-word cloud uncertainties to the number 1 research question priority: raising awareness. Five of the final summary questions were more likely to map to the research uncertainties suggested by participants after having reviewed the word clouds.ConclusionsWord clouds may increase the perspective of underrepresented stakeholders in the research question gathering stage of priority setting partnerships. This may help steer the process towards research questions that are of highest priority for people with the condition.

The mental health and wellbeing impact of a Community Wealth Building programme in England: a difference-in-differences study

Wide differences in health exist between places in the UK, underscored by economic inequalities. Preston, an economically disadvantaged city in England, implemented a new approach to economic development, known as the Community Wealth Building programme. Public and non-profit organisations modified their procurement policies to support the development of local supply chains, improve employment conditions, and increase socially productive use of wealth and assets. We aimed to investigate the effect of this programme on population mental health and wellbeing. Difference-in-differences techniques compared trends in mental health outcomes in Preston, relative to matched control areas before (2011-15) and after (2016-19) the introduction of the programme. Outcomes were antidepressant prescribing, prevalence of depression, and mental health related hospital attendance rates using data provided by National Health Service Digital, the Quality and Outcomes Framework, and the Office for National Statistics. Additional analysis compared local authority measures of life satisfaction, median wages, and employment with synthetic counterfactuals created using Bayesian Structural Time Series. The introduction of the Community Wealth Building programme was associated with reductions in the prescribing of antidepressants (1·3 average daily quantities per person [95% CI 0·72-1·78) and prevalence of depression (2·4 per 1000 population [0·42-4·46]), relative to the control areas. The local population also experienced a 9% improvement in life satisfaction (95% credible interval 0-19·6%) and 11% increase in median wages (1·8-18·9%), relative to expected trends. Associations with employment and mental health related hospital attendance outcomes did not reach statistical significance. During the period in which the Community Wealth Building programme was introduced, there were fewer mental health problems than would have been expected compared with other similar areas, as life satisfaction and economic measures improved. This approach potentially provides an effective model for economic regeneration potentially leading to substantial health benefits. National Institute for Health Research.

The association between genetically elevated polyunsaturated fatty acids and risk of cancer

The causal relevance of polyunsaturated fatty acids (PUFAs) for risk of site-specific cancers remains uncertain. Using a Mendelian randomization (MR) framework, we assessed the causal relevance of PUFAs for risk of cancer in European and East Asian ancestry individuals. We defined the primary exposure as PUFA desaturase activity, proxied by rs174546 at the FADS locus. Secondary exposures were defined as omega 3 and omega 6 PUFAs that could be proxied by genetic polymorphisms outside the FADS region. Our study used summary genetic data on 10 PUFAs and 67 cancers, corresponding to 562,871 cases and 1,619,465 controls, collected by the Fatty Acids in Cancer Mendelian Randomization Collaboration. We estimated odds ratios (ORs) for cancer per standard deviation increase in genetically proxied PUFA exposures. Genetically elevated PUFA desaturase activity was associated (P<0.0007) with higher risk (OR [95% confidence interval]) of colorectal cancer (1.09 [1.07-1.11]), esophageal squamous cell carcinoma (1.16 [1.06-1.26]), lung cancer (1.06 [1.03-1.08]) and basal cell carcinoma (1.05 [1.02-1.07]). There was little evidence for associations with reproductive cancers (OR=1.00 [95% CI: 0.99-1.01]; Pheterogeneity=0.25), urinary system cancers (1.03 [0.99-1.06], Pheterogeneity=0.51), nervous system cancers (0.99 [0.95-1.03], Pheterogeneity=0.92) or blood cancers (1.01 [0.98-1.04], Pheterogeneity=0.09). Findings for colorectal cancer and esophageal squamous cell carcinoma remained compatible with causality in sensitivity analyses for violations of assumptions. Secondary MR analyses highlighted higher omega 6 PUFAs (arachidonic acid, gamma-linolenic acid and dihomo-gamma-linolenic acid) as potential mediators. PUFA biosynthesis is known to interact with aspirin, which increases risk of bleeding and inflammatory bowel disease. In a phenome-wide MR study of non-neoplastic diseases, we found that genetic lowering of PUFA desaturase activity, mimicking a hypothetical intervention to reduce cancer risk, was associated (P<0.0006) with increased risk of inflammatory bowel disease but not bleeding. The PUFA biosynthesis pathway may be an intervention target for prevention of colorectal cancer and esophageal squamous cell carcinoma but with potential for increased risk of inflammatory bowel disease. Cancer Resesrch UK (C52724/A20138, C18281/A19169). UK Medical Research Council (MR/P014054/1). National Institute for Health Research (NIHR202411). UK Medical Research Council (MC_UU_00011/1, MC_UU_00011/3, MC_UU_00011/6, and MC_UU_00011/4). National Cancer Institute (R00 CA215360). National Institutes of Health (U01 CA164973, R01 CA60987, R01 CA72520, U01 CA74806, R01 CA55874, U01 CA164973 and U01 CA164973).

National Institutes of Health Funding to Departments of Orthopaedic Surgery at U.S. Medical Schools from 2015 to 2021.

National Institutes of Health (NIH) funding of orthopaedic surgery departments has historically lagged behind that of other surgical disciplines. In this study, we present an updated analysis of NIH grants awarded to orthopaedic surgery departments at U.S. medical schools and an evaluation of the characteristics of NIH-funded principal investigators (PIs). The NIH Research Portfolio Online Reporting Tools Expenditures and Results (RePORTER) database was queried for grants awarded to orthopaedic surgery departments in the 2015 to 2021 fiscal years. Funding totals were calculated for 4 categories: award mechanism, awarding institute, recipient institute, and PI. Trends in funding from 2015 to 2021 were determined and compared with the annual NIH budget. Funding awarded to orthopaedic surgery departments was compared with awards received by other surgical specialties in 2021. The characteristics of NIH-funded PIs and co-PIs were evaluated. Funding awarded to orthopaedic surgery departments in 2021 was compared with funding in 2014 as reported in a previous study. In 2021, 287 grants were awarded to 187 PIs at 47 orthopaedic surgery departments for a total of $104,710,841, representing 0.4% of the overall NIH budget. The top 5 departments earned $41,750,321 (39.9%) of the total NIH funding for orthopaedic surgery. From 2015 to 2021, total funding increased by 79.7% (p < 0.001), but the rate of increase was not significantly different from that of the overall annual NIH budget (p = 0.469). In 2021, grants were most commonly awarded via the R01 mechanism (70.0% of total funding), with a median annual award of $397,144 (interquartile range [IQR], $335,017 to $491,248). The majority of grants (70.0%) supported basic science research, followed by translational (12.2%), clinical (9.4%), and educational (8.4%) research. NIH funding did not vary by the gender of the PI (p = 0.505), and the proportion of female PIs was significantly greater in 2021 than in 2014 (33.9% versus 20.5%, p = 0.009). Compared with other surgical departments, orthopaedic surgery departments ranked second-lowest in terms of the total NIH funding received in 2021. NIH funding to orthopaedic surgery departments continues to be limited and lags behind that of other surgical subspecialties, which may create challenges in addressing the rising burden of musculoskeletal disease in the U.S. These findings highlight the importance of efforts to identify barriers to grant procurement in orthopaedic surgery.

Effects of sleep disturbance on dyspnoea and impaired lung function following hospital admission due to COVID-19 in the UK: a prospective multicentre cohort study

Sleep disturbance is common following hospital admission both for COVID-19 and other causes. The clinical associations of this for recovery after hospital admission are poorly understood despite sleep disturbance contributing to morbidity in other scenarios. We aimed to investigate the prevalence and nature of sleep disturbance after discharge following hospital admission for COVID-19 and to assess whether this was associated with dyspnoea. CircCOVID was a prospective multicentre cohort substudy designed to investigate the effects of circadian disruption and sleep disturbance on recovery after COVID-19 in a cohort of participants aged 18 years or older, admitted to hospital for COVID-19 in the UK, and discharged between March, 2020, and October, 2021. Participants were recruited from the Post-hospitalisation COVID-19 study (PHOSP-COVID). Follow-up data were collected at two timepoints: an early time point 2-7 months after hospital discharge and a later time point 10-14 months after hospital discharge. Sleep quality was assessed subjectively using the Pittsburgh Sleep Quality Index questionnaire and a numerical rating scale. Sleep quality was also assessed with an accelerometer worn on the wrist (actigraphy) for 14 days. Participants were also clinically phenotyped, including assessment of symptoms (ie, anxiety [Generalised Anxiety Disorder 7-item scale questionnaire], muscle function [SARC-F questionnaire], dyspnoea [Dyspnoea-12 questionnaire] and measurement of lung function), at the early timepoint after discharge. Actigraphy results were also compared to a matched UK Biobank cohort (non-hospitalised individuals and recently hospitalised individuals). Multivariable linear regression was used to define associations of sleep disturbance with the primary outcome of breathlessness and the other clinical symptoms. PHOSP-COVID is registered on the ISRCTN Registry (ISRCTN10980107). 2320 of 2468 participants in the PHOSP-COVID study attended an early timepoint research visit a median of 5 months (IQR 4-6) following discharge from 83 hospitals in the UK. Data for sleep quality were assessed by subjective measures (the Pittsburgh Sleep Quality Index questionnaire and the numerical rating scale) for 638 participants at the early time point. Sleep quality was also assessed using device-based measures (actigraphy) a median of 7 months (IQR 5-8 months) after discharge from hospital for 729 participants. After discharge from hospital, the majority (396 [62%] of 638) of participants who had been admitted to hospital for COVID-19 reported poor sleep quality in response to the Pittsburgh Sleep Quality Index questionnaire. A comparable proportion (338 [53%] of 638) of participants felt their sleep quality had deteriorated following discharge after COVID-19 admission, as assessed by the numerical rating scale. Device-based measurements were compared to an age-matched, sex-matched, BMI-matched, and time from discharge-matched UK Biobank cohort who had recently been admitted to hospital. Compared to the recently hospitalised matched UK Biobank cohort, participants in our study slept on average 65 min (95% CI 59 to 71) longer, had a lower sleep regularity index (-19%; 95% CI -20 to -16), and a lower sleep efficiency (3·83 percentage points; 95% CI 3·40 to 4·26). Similar results were obtained when comparisons were made with the non-hospitalised UK Biobank cohort. Overall sleep quality (unadjusted effect estimate 3·94; 95% CI 2·78 to 5·10), deterioration in sleep quality following hospital admission (3·00; 1·82 to 4·28), and sleep regularity (4·38; 2·10 to 6·65) were associated with higher dyspnoea scores. Poor sleep quality, deterioration in sleep quality, and sleep regularity were also associated with impaired lung function, as assessed by forced vital capacity. Depending on the sleep metric, anxiety mediated 18-39% of the effect of sleep disturbance on dyspnoea, while muscle weakness mediated 27-41% of this effect. Sleep disturbance following hospital admission for COVID-19 is associated with dyspnoea, anxiety, and muscle weakness. Due to the association with multiple symptoms, targeting sleep disturbance might be beneficial in treating the post-COVID-19 condition. UK Research and Innovation, National Institute for Health Research, and Engineering and Physical Sciences Research Council.