National Institute For Health Research Research Articles

“I am in favour of organ donation, but I feel you should opt-in”—qualitative analysis of the #options 2020 survey free-text responses from NHS staff toward opt-out organ donation legislation in England

BackgroundIn May 2020, England moved to an opt-out organ donation system, meaning adults are presumed to be an organ donor unless within an excluded group or have opted-out. This change aims to improve organ donation rates following brain or circulatory death. Healthcare staff in the UK are supportive of organ donation, however, both healthcare staff and the public have raised concerns and ethical issues regarding the change. The #options survey was completed by NHS organisations with the aim of understanding awareness and support of the change. This paper analyses the free-text responses from the survey.MethodsThe #options survey was registered as a National Institute of Health Research (NIHR) portfolio trial [IRAS 275992] 14 February 2020, and was completed between July and December 2020 across NHS organisations in the North-East and North Cumbria, and North Thames. The survey contained 16 questions of which three were free-text, covering reasons against, additional information required and family discussions. The responses to these questions were thematically analysed.ResultsThe #options survey received 5789 responses from NHS staff with 1404 individuals leaving 1657 free-text responses for analysis. The family discussion question elicited the largest number of responses (66%), followed by those against the legislation (19%), and those requiring more information (15%). Analysis revealed six main themes with 22 sub-themes.ConclusionsThe overall #options survey indicated NHS staff are supportive of the legislative change. Analysis of the free-text responses indicates that the views of the NHS staff who are against the change reflect the reasons, misconceptions, and misunderstandings of the public. Additional concerns included the rationale for the change, informed decision making, easy access to information and information regarding organ donation processes. Educational materials and interventions need to be developed for NHS staff to address the concepts of autonomy and consent, organ donation processes, and promote family conversations. Wider public awareness campaigns should continue to promote the positives and refute the negatives thus reducing misconceptions and misunderstandings.Trial registrationNational Institute of Health Research (NIHR) [IRAS 275992].

Changes in hospital mortality in patients with cancer during the COVID-19 pandemic (ISARIC-CCP-UK): a prospective, multicentre cohort study

Patients with cancer are at greater risk of dying from COVID-19 than many other patient groups. However, how this risk evolved during the pandemic remains unclear. We aimed to determine, on the basis of the UK national pandemic protocol, how factors influencing hospital mortality from COVID-19 could differentially affect patients undergoing cancer treatment. We also examined changes in hospital mortality and escalation of care in patients on cancer treatment during the first 2 years of the COVID-19 pandemic in the UK. We conducted a prospective cohort study of patients aged older than 19 years and admitted to 306 health-care facilities in the UK with confirmed SARS-CoV-2 infection, who were enrolled in the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol (CCP) across the UK from April 23, 2020, to Feb 28, 2022; this analysis included all patients in the complete dataset when the study closed. The primary outcome was 30-day in-hospital mortality, comparing patients on cancer treatment and those without cancer. The study was approved by the South Central-Oxford C Research Ethics Committee in England (Ref: 13/SC/0149) and the Scotland A Research Ethics Committee (Ref 20/SS/0028), and is registered on the ISRCTN Registry (ISRCTN66726260). 177 871 eligible adult patients either with no history of cancer (n=171 303) or on cancer treatment (n=6568) were enrolled; 93 205 (52·4%) were male, 84 418 (47·5%) were female, and in 248 (13·9%) sex or gender details were not specified or data were missing. Patients were followed up for a median of 13 (IQR 6-21) days. Of the 6568 patients receiving cancer treatment, 2080 (31·7%) died at 30 days, compared with 30 901 (18·0%) of 171 303 patients without cancer. Patients aged younger than 50 years on cancer treatment had the highest age-adjusted relative risk (hazard ratio [HR] 5·2 [95% CI 4·0-6·6], p<0·0001; vs 50-69 years 2·4 [2·2-2·6], p<0·0001; 70-79 years 1·8 [1·6-2·0], p<0·0001; and >80 years 1·5 [1·3-1·6], p<0·0001) but a lower absolute risk (51 [6·7%] of 763 patients <50 years died compared with 459 [30·2%] of 1522 patients aged >80 years). In-hospital mortality decreased for all patients during the pandemic but was higher for patients on cancer treatment than for those without cancer throughout the study period. People with cancer have a higher risk of mortality from COVID-19 than those without cancer. Patients younger than 50 years with cancer treatment have the highest relative risk of death. Continued action is needed to mitigate the poor outcomes in patients with cancer, such as through optimising vaccination, long-acting passive immunisation, and early access to therapeutics. These findings underscore the importance of the ISARIC-WHO pandemic preparedness initiative. National Institute for Health Research and the Medical Research Council.

Incidence of urinary infections and pharmacological sensitivity in elective urine samples in a prospective cohort from Luanda, Angola

This prospective cohort study evaluated 107 urine samples from patients suspected of urinary tract infection (UTI) treated at Cajueiros General Hospital in Angola from January to March 2023. Inclusion criteria involved obtaining urine samples for clinical examinations from adult patients with suspected UTI, regardless of gender, age, or previous clinical condition. The samples were transported to the reference laboratory of the National Institute of Health Research for microbiological evaluation and antibiotic sensitivity testing using the VITEK 2 system. Of the 107 patients evaluated, 39.3% (n= 42) showed bacterial growth in their urine. Escherichia coli was the predominant pathogen (23.8%), followed by Sphingomonas paucimobilis, Pseudomonas luteola, and Klebsiella pneumoniae. Antimicrobial resistance was observed, with ampicillin (90.5%) being the most resistant, while imipenem (95.2%) and ertapenem (90.5%) exhibited high sensitivity. Statistical analysis revealed common clinical characteristics, such as fever (61.7%) and dysuria (73.8%). This study provides a comprehensive understanding of microbial ecology in urinary infections, highlighting the prevalence of pathogens and antibiotic resistance patterns in a specific patient population in Angola. Importantly, this research represents the first prospective study of its kind in Angola.

Machine Learning-based Analysis of Publications Funded by the National Institutes of Health's Initial COVID-19 Pandemic Response.

The National Institutes of Health (NIH) mobilized more than $4 billion in extramural funding for the COVID-19 pandemic. Assessing the research output from this effort is crucial to understanding how the scientific community leveraged federal funding and responded to this public health crisis. NIH-funded COVID-19 grants awarded between January 2020 and December 2021 were identified from NIH Research Portfolio Online Reporting Tools Expenditures and Results using the "COVID-19 Response" filter. PubMed identifications of publications under these grants were collected and the NIH iCite tool was used to determine citation counts and focus (eg, clinical, animal). iCite and the NIH's LitCOVID database were used to identify publications directly related to COVID-19. Publication titles and Medical Subject Heading terms were used as inputs to a machine learning-based model built to identify common topics/themes within the publications. We evaluated 2401 grants that resulted in 14 654 publications. The majority of these papers were published in peer-reviewed journals, though 483 were published to preprint servers. In total, 2764 (19%) papers were directly related to COVID-19 and generated 252 029 citations. These papers were mostly clinically focused (62%), followed by cell/molecular (32%), and animal focused (6%). Roughly 60% of preprint publications were cell/molecular-focused, compared with 26% of nonpreprint publications. The machine learning-based model identified the top 3 research topics to be clinical trials and outcomes research (8.5% of papers), coronavirus-related heart and lung damage (7.3%), and COVID-19 transmission/epidemiology (7.2%). This study provides key insights regarding how researchers leveraged federal funding to study the COVID-19 pandemic during its initial phase.

Recent changes in growth trajectories: a population-based cohort study of over 5 million Brazilian children born between 2001 and 2014

There is limited evidence on recent trends in childhood growth trajectories in Low-/middle-income countries. We investigated how age-trajectories for height and Body Mass Index (BMI) have changed among Brazilian children born in two different time periods after2000. We used a population-based cohort (part of the "Cohort of 100-Million Brazilians") created by the linkage of three Brazilian administrative databases: the Cadastro Único of the Federal Government, the National System of Live Births and the National Nutritional and Food Surveillance System. We included longitudinal data on 5,750,214 children who were 3 to <10 years of age and born between 2001 and 2014 (20,209,133 observations). We applied fractional polynomial models with random-effects to estimate mean height and BMI trajectories for children. Compared to children born in 2001-2007, the cohort born in 2008-2014 were on average taller, by a z-score of 0.15 in boys and 0.12 in girls. Their height trajectories shifted upwards, by approximately 1cm in both sexes. Levels of BMI increased little, by a z-score of 0.06 (boys) and 0.04 (girls). Mean BMI trajectories also changed little. However, the prevalence of overweight/obesity increased between cohorts, e.g., from 26.8% to 30% in boys and 23.9%-26.6% in girls aged between 5 and <10 years. An increase of 1cm in mean height of Brazilian children during a short period indicates the improvement in maternal and child health, especially those from low-income families due to the new health and welfare policies in Brazil. Although mean BMI changed little, the prevalence of child overweight/obesity slightly increased and remained high. This work was supported by National Council for Scientific and Technological Development - CNPq; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES; National Institute for Health Research (NIHR) Great Ormond Street Hospital Biomedical Research Centre; Society for the Study of Human Biology; Fundação de Amparo à Pesquisa do Estado de Minas Gerais - FAPEMIG; Departamento de Ciência e Tecnologia da Secretaria de Ciência, Tecnologia, Inovação e Complexo da Saúde do Ministério da Saúde - Decit/SECTICS/MS. The study also used resources from the Centre for Data and Knowledge Integration for Health (CIDACS), which receives funding from the Bill & Melinda Gates Foundation, the Wellcome Trust, the Health Surveillance Secretariat of the Ministry of Health and the Secretariat of Science and Technology of the State of Bahia (SECTI-BA).

Adapting, restarting, and terminating a randomised control trial for people with cystic fibrosis: Reflections on the impact of the COVID-19 pandemic upon research in a clinical population

BackgroundHabitual physical activity (PA) and exercise form a cornerstone of the management of cystic fibrosis (CF), a genetically inherited pulmonary and digestive condition – whereby telehealth platforms have been proposed as a mechanism to engage remotely people with CF in PA and exercise. MethodsTo test this, in early 2020, the ‘ActivOnline: Physical Activity in Cystic Fibrosis Trial’ (ActiOn PACT) randomised control trial was established to examine whether an online intervention was effective at increasing PA in adolescents and adults with CF. ResultsThe emergence of the COVID-19 pandemic in 2020 forced this trial to be paused and modified, with the adoption of online recruitment and remote assessment of outcome measures. Despite such adaptations in accord with frameworks developed by the National Institute for Health Research, this trial failed to recruit and was subsequently terminated. ConclusionsThis article details the authors reflections upon the proposed reasons for lack of recruitment, including improved technology and medications for people with CF, and contextualises this finding in relation to the wider issue of non-reporting of trial results in clinical research.

Factors Associated with Research Productivity and National Institutes of Health Funding in Academic Otology.

Bibliometrics, such as the Hirsch index (h-index) and the more recently developed relative citation ratio (RCR), are utilized to evaluate research productivity. Our study evaluates demographics, research productivity, and National Institutes of Health (NIH) funding in academic otology. Academic otologists were identified, and their demographics were collected using institutional faculty profiles (N = 265). Funding data were obtained using the NIH Research Portfolio Online Reporting Tools Expenditures and Reports Database. The h-index was calculated using Scopus and mean (m-RCR) and weighted RCR (w-RCR) were calculated using the NIH iCite tool. H-index (aOR 1.18, 95% CI 1.10-1.27, p < 0.001), but not m-RCR (aOR 1.50, 95% CI 0.97-2.31, p = 0.069) or w-RCR (aOR 1.00, 95% CI 0.99-1.00, p = 0.231), was associated with receiving NIH funding. Men had greater h-index (16 vs. 9, p < 0.001) and w-RCR (51.8 vs. 23.0, p < 0.001), but not m-RCR (1.3 vs. 1.3, p = 0.269) than women. Higher academic rank was associated with greater h-index and w-RCR (p < 0.001). Among assistant professors, men had greater h-index than women (9.0 vs. 8.0, p = 0.025). At career duration 11-20 years, men had greater h-index (14.0 vs. 8.0, p = 0.009) and w-RCR (52.7 vs. 25.8, p = 0.022) than women. The h-index has a strong relationship with NIH funding in academic otology. Similar h-index, m-RCR, and w-RCR between men and women across most academic ranks and career durations suggests production of similarly impactful research. The m-RCR may correct some deficiencies of time-dependent bibliometrics and its consideration in academic promotion and research funding allocation may promote representation of women in otology. N/A Laryngoscope, 134:3786-3794, 2024.

Adoption of routine surgical video recording: a nationwide freedom of information act request across England and Wales

Surgical video contains data with significant potential to improve surgical outcome assessment, quality assurance, education, and research. Current utilisation of surgical video recording is unknown and related policies/governance structures are unclear. A nationwide Freedom of Information (FOI) request concerning surgical video recording, technology, consent, access, and governance was sent to all acute National Health Service (NHS) trusts/boards in England/Wales between 20th February and 20th March2023. 140/144 (97.2%) trusts/boards in England/Wales responded to the FOI request. Surgical procedures were routinely recorded in 22 trusts/boards. The median estimate of consultant surgeons routinely recording their procedures was 20%. Surgical video was stored on internal systems (n=27), third-party products (n=29), and both (n=9). 32/140 (22.9%) trusts/boards ask for consent to record procedures as part of routine care. Consent for recording included non-clinical purposes in 55/140 (39.3%) trusts/boards. Policies for surgeon/patient access to surgical video were available in 48/140 (34.3%) and 32/140 (22.9%) trusts/boards, respectively. Surgical video was used for non-clinical purposes in 64/140 (45.7%) trusts/boards. Governance policies covering surgical video recording, use, and/or storage were available from 59/140 (42.1%) trusts/boards. There is significant heterogeneity in surgical video recording practices in England and Wales. A minority of trusts/boards routinely record surgical procedures, with large variation in recording/storage practices indicating scope for NHS-wide coordination. Revision of surgical video consent, accessibility, and governance policies should be prioritised by trusts/boards to protect key stakeholders. Increased availability of surgical video is essential for patients and surgeons to maximally benefit from the ongoing digital transformation of surgery. KL is supported by an NIHR Academic Clinical Fellowship and acknowledges infrastructure support for this research from the National Institute for Health Research (NIHR) Imperial Biomedical Research Centre (BRC).

Detection of endometrial cancer in cervico-vaginal fluid and blood plasma: leveraging proteomics and machine learning for biomarker discovery

The anatomical continuity between the uterine cavity and the lower genital tract allows for the exploitation of uterine-derived biomaterial in cervico-vaginal fluid for endometrial cancer detection based on non-invasive sampling methodologies. Plasma is an attractive biofluid for cancer detection due to its simplicity and ease of collection. In this biomarker discovery study, we aimed to identify proteomic signatures that accurately discriminate endometrial cancer from controls in cervico-vaginal fluid and blood plasma. Blood plasma and Delphi Screener-collected cervico-vaginal fluid samples were acquired from symptomatic post-menopausal women with (n=53) and without (n=65) endometrial cancer. Digitised proteomic maps were derived for each sample using sequential window acquisition of all theoretical mass spectra (SWATH-MS). Machine learning was employed to identify the most discriminatory proteins. The best diagnostic model was determined based on accuracy and model parsimony. A protein signature derived from cervico-vaginal fluid more accurately discriminated cancer from control samples than one derived from plasma. A 5-biomarker panel of cervico-vaginal fluid derived proteins (HPT, LG3BP, FGA, LY6D and IGHM) predicted endometrial cancer with an AUC of 0.95 (0.91-0.98), sensitivity of 91% (83%-98%), and specificity of 86% (78%-95%). By contrast, a 3-marker panel of plasma proteins (APOD, PSMA7 and HPT) predicted endometrial cancer with an AUC of 0.87 (0.81-0.93), sensitivity of 75% (64%-86%), and specificity of 84% (75%-93%). The parsimonious model AUC values for detection of stage I endometrial cancer in cervico-vaginal fluid and blood plasma were 0.92 (0.87-0.97) and 0.88 (0.82-0.95) respectively. Here, we leveraged the natural shed of endometrial tumours to potentially develop an innovative approach to endometrial cancer detection. We show proof of principle that endometrial cancers secrete unique protein signatures that can enable cancer detection via cervico-vaginal fluid assays. Confirmation in a larger independent cohort is warranted. Cancer Research UK, Blood Cancer UK, National Institute for Health Research.

Individual patient data meta-analysis of the effects of fluoxetine on functional outcomes after acute stroke.

Three large randomized controlled trials of fluoxetine for stroke recovery have been performed. We performed an individual patient data meta-analysis (IPDM) on the combined data. Fixed effects meta-analyses were performed on the combined data set, for the primary outcome (modified Rankin scale (mRS) at 6 months), and secondary outcomes common to the individual trials. As a sensitivity analysis, summary statistics from each trial were created and combined. The three trials recruited a combined total of 5907 people (mean age 69.5 years (SD 12.3), 2256 (38%) females, 2-15 days post-stroke) from Australia, New Zealand, United Kingdom, Sweden, and Vietnam; and randomized them to fluoxetine 20 mg daily or matching placebo for 6 months. Data on 5833 (98.75%) were available at 6 months. The adjusted ordinal comparison of mRS was similar in the two groups (common OR 0.96, 95% CI 0.87 to 1.05, p = 0.37). There were no statistically significant interactions between the minimization variables (baseline probability of being alive and independent at 6 months, time to treatment, motor deficit, or aphasia) and pre-specified subgroups (including age, pathological type, inability to assess mood, proxy or patient consent, baseline depression, country). Fluoxetine increased seizure risk (2.64% vs 1.8%, p = 0.03), falls with injury (6.26% vs 4.51%, p = 0.03), fractures (3.15% vs 1.39%, p < 0.0001) and hyponatremia (1.22% vs 0.61%, p = 0.01) but reduced new depression (10.05% vs 13.42%, p < 0.0001). At 12 months, there was no difference in adjusted mRS (n = 5760; common OR 0.98, 95% CI 0.89 to 1.07). Sensitivity analyses gave the same results. Fluoxetine 20 mg daily for 6 months did not improve functional recovery. It increased seizures, falls with injury, and bone fractures but reduced depression frequency at 6 months.

Effects of foam roller on pain intensity in individuals with chronic and acute musculoskeletal pain: a systematic review of randomized trials

ObjectiveTo analyze the effects of using foam roller on pain intensity in individuals with chronic and acute musculoskeletal pain.MethodsThis systematic review was registered in the National Institute for Health Research’s prospective online registry of systematic reviews (PROSPERO) under CRD42023456841. The databases Pubmed, Medline (via Ovid), Embase, BVS, and PEDro (Physiotherapy Evidence Database) were consulted to carry out this systematic review. Notably, the records of clinical trials characterized as eligible were manually searched. The search terms were: (foam rolling OR foam rolling vibration) AND (acute musculoskeletal pain) AND (chronic musculoskeletal pain). The search was performed until August 22, 2023. For the analysis of the methodological quality, the PEDro scale was used for each of the manuscripts included in the systematic review. Due to the heterogeneity in the studies included in this systematic review, performing a meta-analysis of the analyzed variables was impossible.ResultsOnly six manuscripts were eligible for data analysis. The type of FR used was non-vibrational, being applied by a therapist in only one of the manuscripts. With an application time ranging from at least 45 s to 15 min, the non-vibrational FR was applied within a day up to six weeks. Using the PEDro scale, scores were assigned that varied between 4 and 8 points, with an average of 6 ± 1.29 points. Only two randomized clinical trials found a significant benefit in pain intensity of adding FR associated with a therapeutic exercise protocol in individuals with patellofemoral pain syndrome and chronic neck pain.ConclusionThe results of this systematic review do not elucidate or reinforce the clinical use of FR in pain intensity in individuals with chronic and acute musculoskeletal pain.

Co-producing an online patient public community research hub: a qualitative study exploring the perspectives of national institute for health research (NIHR) research champions in England

BackgroundPatient and Public Involvement and Engagement (PPIE) should be embedded as part of researchers’ everyday practice. However, this can be challenging. Creating a digital presence for PPIE as part of Higher Education Institutes’ (HEIs) infrastructure may be one way of supporting this. This can support how information is made available to patients and members of the public, but relatively little is known about how HEIs can best do this. Our aim was to develop a university website for patients and members of the public to learn about ways to get actively involved in research and be able to access the results of health and social care research.MethodsThis project involved working as partners with five National Institute for Health and Care Research (NIHR) Research Champions. NIHR Research Champions are volunteers who raise awareness and share experiences about health and social care research. Content of a prototype Patient Public Community Research Hub website was co-produced with the Research Champions, and then 15 NIHR Research Champions from across England were asked for their views about the website.FindingsThe information collected told us that the Patient Public Community Research Hub was viewed as being beneficial for increasing visibility of PPIE opportunities and sharing the findings of studies though needs further work: to make the information more user-friendly; to improve the methods for directing people to the site and to create new ways of connecting with people. It provides a foundation for further co-development and evaluation. A set of recommendations has been developed that may be of benefit to other HEIs and organisations who are committed to working with patients and members of the public.

Sensitivity profile of pathogens identified in the diagnosis of urinary infection by uroculture carried out at the National Institute for Health Research, Luanda/Angola, during the pre - pandemic, intra - pandemic and post - pandemic of COVID 19

Urinary tract infection (UTI) is an infectious disease that affects any part of the urinary system, including the kidneys, ureters, bladder, and urethra. Antimicrobial resistance (AMR) is currently a public health problem. To understand the antibiotic susceptibility profile of microorganisms isolated in urine samples at the reference microbiology laboratory in Luanda/Angola from 2016-2022 (pre-pandemic, pandemic, and post-pandemic). Methodology: A descriptive, quantitative, documentary study was carried out using a survey of secondary data, based on the results of urocultures from patients with a suspected diagnosis of UTI. A total of 2,800 (50.99%) were studied (n=5,491) and confirmed as having a UTI. From 2016 to 2019, 2,060 were confirmed; in 2020, 51 cases were investigated and 24 (0.86%) were confirmed. In 2022, corresponding to the period after the COVID-19 pandemic, a total of 246 patients (8.78%) had a confirmed urinary tract infection. In general, in all periods, the most sensitive drugs were amikacin, fosfomycin, norfloxacin, nalidixic acid, tobramycin, akanamycin and cefotaxime. Females and the E. coli strain followed by proteus vulgaris and mirabilis and the 20-29 and 30-39 age groups were the most prevalent.

Remote digital cognitive assessment reveals cognitive deficits related to hippocampal atrophy in autoimmune limbic encephalitis: a cross-sectional validation study

Autoimmune limbic encephalitis (ALE) is a neurological disease characterised by inflammation of the limbic regions of the brain, mediated by pathogenic autoantibodies. Because cognitive deficits persist following acute treatment of ALE, the accurate assessment of long-term cognitive outcomes is important for clinical assessments and trials. However, evaluating cognition is costly and an unmet need exists for validated digital methods. In this cross-sectional validation study, we investigated whether a remote digital platform could identify previously characterised cognitive impairments in patients with chronic ALE and whether digital metrics would correlate with standard neuropsychological assessment and hippocampal volume. Patients with ALE who had a chronic and stable presentation and received a clinical diagnosis of ALE were recruited for this study. The cognitive performance of 21 patients with ALE and 54 age-matched healthy controls - enrolled via the University of Oxford (UK) Cognitive Neurology Lab testing programme - was assessed with a battery of 12 cognitive tasks from the Cognitron online platform. The platform was optimised with National Institute for Health and Care Research (NIHR) support to be deliverable remotely to elderly and patient groups. The primary outcome measure was behavioural performance and corresponding neuroimaging and neuropsychological assessment metrics. Between February 15, 2021, and April 21, 2022, 21 patients with ALE (mean age 63.01 years, 14 males) and 54 healthy controls (mean age 65.56 years, 23 males) completed the digital cognitive assessment. Patients with ALE performed significantly worse in memory, visuospatial abilities, executive function, and language. No impairments in digit & spatial span, target detection (attention) and emotion discrimination were observed. The global score on the online cognitive tasks correlated significantly with the established Addenbrooke's Cognitive Examination III (ACE) pen-and-paper test. Deficits in visuospatial processing and language were identified in ALE compared to controls using remote digital testing but not using the ACE, highlighting higher sensitivity of computerised testing to residual cognitive impairment. Finally, the hippocampal volumes of patients with ALE and healthy controls correlated with online cognitive scores. These findings demonstrate that subtle cognitive deficits in patients with chronic ALE, who often show full recovery in measures of disability and dependence on daily activities, are detectable using a remote online platform, which also relates to hippocampal atrophy. Such methods may facilitate the characterisation of cognitive profiles in complex neurological diseases. Future longitudinal studies designed to assess the utility of such digital methods for further clinical characterisation are needed. The Wellcome Trust, Medical Research Council, National Institute for Health Research, Rhodes Scholarship, and the Berrow Foundation Scholarship.

Autologous Stem Cell-derived Therapies for Androgenetic Alopecia: A Systematic Review of Randomized Control Trials on Efficacy, Safety, and Outcomes.

Androgenic alopecia (AGA), a prevalent and extensively studied condition characterized by hair loss, presents a significant global issue for both men and women. Stem cell therapy has emerged as a promising therapeutic approach for AGA due to its regenerative and immunomodulatory properties. The primary objective of this systematic review was to assess the current literature on the efficacy and safety of cellular and acellular stem cell-derived therapies in the management of AGA. A computerized literature search was conducted in ClinicalTrials.gov, PubMed, and Cochrane Library in October 2023. The online screening process was performed by three independent reviewers with the Covidence tool. The protocol was reported using the Preferred Reporting Items for Systematic Review and Meta-Analyses, and it was registered at the International Prospective Register of Systematic Reviews of the National Institute for Health Research. The search yielded 53 articles from 2013 to 2023. Twelve randomized controlled trials were included. Stem cells and their derivatives were isolated from human adipose tissue, hair follicles, bone marrow, umbilical cord blood, and exfoliated deciduous teeth. These trials showed that stem cell-derived treatments can promote hair regeneration and density. Both cellular and acellular stem cell-based therapies are safe and effective in improving hair regeneration and density in AGA patients. Although the outcomes may be temporary in some cases, regenerative treatments may become useful adjuncts in combination with traditional methods of hair transplantation. Future research should focus on protocol optimization to enhance long-term patient outcomes.

Olanzapine for young PEople with aNorexia nervosa (OPEN): A protocol for an open-label feasibility study.

Antipsychotics are routinely prescribed off-label for anorexia nervosa (AN) despite limited evidence. This article presents a protocol of a study aiming to assess the feasibility of a future definitive trial on olanzapine in young people with AN. In an open-label, one-armed feasibility study, 55 patients with AN or atypical AN, aged 12-24, receiving outpatient, inpatient or day-care treatment who are considered for olanzapine treatment will be recruited from NHS sites based in England. Assessments will be conducted at screening, baseline and at 8-, 16weeks, 6- and 12months. Primary feasibility parameters will be proportions of patients who agree to take olanzapine and who adhere to treatment and complete study assessments. Qualitative methods will be used to explore acceptability of the intervention and study design. Secondary feasibility parameters will be changes in body mass index, psychopathology, side effects, health-related quality of life, carer burden and proportion of participants who would enrol in a future randomised controlled trial. The study is funded by the National Institute for Health Research via Health Technology Assessment programme. Olanzapine for young PEople with aNorexia nervosa will inform a future randomised controlled trial on the efficacy and safety of prescribing olanzapine in young people with AN.

Integrating multiple lines of evidence to assess the effects of maternal BMI on pregnancy and perinatal outcomes

BackgroundHigher maternal pre-pregnancy body mass index (BMI) is associated with adverse pregnancy and perinatal outcomes. However, whether these associations are causal remains unclear.MethodsWe explored the relation of maternal pre-/early-pregnancy BMI with 20 pregnancy and perinatal outcomes by integrating evidence from three different approaches (i.e. multivariable regression, Mendelian randomisation, and paternal negative control analyses), including data from over 400,000 women.ResultsAll three analytical approaches supported associations of higher maternal BMI with lower odds of maternal anaemia, delivering a small-for-gestational-age baby and initiating breastfeeding, but higher odds of hypertensive disorders of pregnancy, gestational hypertension, preeclampsia, gestational diabetes, pre-labour membrane rupture, induction of labour, caesarean section, large-for-gestational age, high birthweight, low Apgar score at 1 min, and neonatal intensive care unit admission. For example, higher maternal BMI was associated with higher risk of gestational hypertension in multivariable regression (OR = 1.67; 95% CI = 1.63, 1.70 per standard unit in BMI) and Mendelian randomisation (OR = 1.59; 95% CI = 1.38, 1.83), which was not seen for paternal BMI (OR = 1.01; 95% CI = 0.98, 1.04). Findings did not support a relation between maternal BMI and perinatal depression. For other outcomes, evidence was inconclusive due to inconsistencies across the applied approaches or substantial imprecision in effect estimates from Mendelian randomisation.ConclusionsOur findings support a causal role for maternal pre-/early-pregnancy BMI on 14 out of 20 adverse pregnancy and perinatal outcomes. Pre-conception interventions to support women maintaining a healthy BMI may reduce the burden of obstetric and neonatal complications.FundingMedical Research Council, British Heart Foundation, European Research Council, National Institutes of Health, National Institute for Health Research, Research Council of Norway, Wellcome Trust.

OP11 Exploring the potential clinical utility of NUDT15 pharmacogenetic testing in clinical practice: a ‘focused reverse phenotyping’ study in the UK IBD Bioresource

Abstract Background In a previous study we recruited patients with inflammatory bowel disease (IBD) and a history of thiopurine induced myelosuppression (TIM) and identified associated variants in NUDT15. This widely used phenotype-first approach, is limited by ascertainment and recall bias, which impacts understanding of penetrance, expressivity, and variant pathogenicity that are key to clinical implementation. The United Kingdom (UK) National Institute for Health Research (NIHR) IBD Bioresource allows investigators to select large numbers of subjects based on genomic variants of interest, rather than phenotypes, to overcome these biases. Using this ‘focused reverse phenotyping’ approach we sought to investigate the cumulative 6-month risk of myelosuppression in patients with NUDT15 variants. Methods Cases and controls were identified from whole exome sequencing data. Cases included all participants with a loss of function NUDT15 variant (*2, *3, *4, *5, *6 and *9). Control subjects were selected based on wild-type carriage of NUDT15 and TPMT, matched for ethnicity. Our primary outcome measure was time to TIM. Myelosuppression was defined as a white cell count (WCC) &amp;lt;3.5x109/L or a neutrophil count &amp;lt;2.0x109/L that occurred within six months of achieving the maximum thiopurine dose, or in the absence of blood test results, a decision to reduce the dose of or withdraw the thiopurine due to myelosuppression. Severe myelosuppression was defined as a WCC &amp;lt;2.5x109/L or neutrophil count &amp;lt;1.0x109/L and a decision to either reduce the dose of or stop the thiopurine. Results We screened 23,082 patients recruited to the UK NIHR IBD bioresource with whole exome sequence data and identified 451 patients with a loss of function NUDT15 variant. We matched, based on ethnicity, these patients to 916 controls. Overall, 271/21,136 (1.3%) Caucasians and 127/1,089 (11.7%) South Asian carried an NUDT15 variant allele. 239/451 (60%) cases had a history of thiopurine exposure. The median weight-adjusted maximum thiopurine dose amongst cases and controls was 1.78 and 1.79 mg/kg/day, respectively. The time to myelosuppression was shorter in patients with NUDT15 variants as shown in Figure 1. The risk of myelosuppression, severe myelosuppression, and hospitalisation was also higher in patients with NUDT15 variants as shown in table 1. Conclusion In this reverse phenotyping study, the time to myelosuppression was significantly shorter in patients who carried a loss of function NUDT15 variant. The overall risk of myelosuppression was lower than previously observed in phenotype-first studies. Prior to implementation further analysis of the cost-effectiveness of NUDT15 testing is required.

Brain infection by SARS-CoV-2: Lifelong consequences

Brain infection by SARS-CoV-2: Lifelong consequences The WATCH team, founded to elucidate the role played by specialized brain cells called tanycytes in various physiological processes, has been investigating how and where the SARS-CoV-2 virus infects the brain, and some long-term consequences of this neuro-invasion. The European Research Council (ERC) Synergy project WATCH (Well-Aging and the Tanycytic Control of Health) brings together the teams of three principal investigators: Vincent Prevot, a neuroendocrinologist working for the French National Health Research Institute (INSERM) in Lille, France; Markus Schwaninger, a neurologist at the University of Lübeck, Germany; and Ruben Nogueiras, an expert in molecular metabolism at the University of Santiago de Compostela in Spain. Together, they are researching how tanycytes – highly specialized cells residing in a tiny part of the brain called the hypothalamus – regulate various physiological processes.

‘A commitment to Equality, Diversity and Inclusion’: a conceptual framework for equality of opportunity in Patient and Public Involvement in research

Many research institutions and funders have recently stated their commitment to actively support and promote ‘Equality, Diversity and Inclusion’ (EDI) in various aspects of health research including Patient and Public Involvement (PPI). However, translating this commitment into specific research projects presents significant challenges that existing approaches, practical guidelines and initiatives have not adequately addressed. In this paper, we explore how the lack of clear justifications for the EDI commitment in existing guidelines inadvertently complicates the work of those involved with PPI and we stress the need for conceptual clarity for any EDI effort to yield meaningful results. Our focus centres on the first principle of the EDI discourse, ‘equality’, particularly in the form of ‘equality of opportunity’ as outlined in current guidance provided by the National Institute of Health Research in the United Kingdom. We examine challenges related to justifying and implementing a general, unspecified commitment to equality of opportunity and explain that this reflects a lack of consensus regarding the moral value of PPI in research – a profound problem that remains unaddressed. We then discuss how the presence of several opposing moral perspectives on PPI, makes determining the most appropriate way of addressing barriers to involvement complex and controversial, raising ethical implications for the work of health researchers, PPI specialists and coordinators. Finally we make suggestions on how future research can enrich the concept of ‘equality of opportunity’ in PPI and improve practice. While our primary focus is on the NIHR, a strong advocate of PPI in research, this analysis will point to normative and ethical considerations that may be relevant to other research institutions and funding organisations aiming to promote equality of opportunity in their public and patient involvement strategies.