National Institute For Health Research Research Articles

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.

The intersection of health and housing: Analysis of the research portfolios of the National Institutes of Health, Centers for Disease Control and Prevention, and U.S. Department of Housing and Urban Development.

Housing is a major social determinant of health that affects health status and outcomes across the lifespan. An interagency portfolio analysis assessed the level of funding invested in "health and housing research" from fiscal years (FY) 2016-2020 across the National Institutes of Health (NIH), the United States Department of Housing and Urban Development (HUD), and the Centers for Disease Control and Prevention (CDC) to characterize the existing health and housing portfolio and identify potential areas for additional research and collaboration. We identified NIH, HUD, and CDC research projects that were relevant to both health and housing and characterized them by housing theme, health topic, population, and study design. We organized the assessment of the individual housing themes by four overarching housing-to-health pathways. From FY 2016-2020, NIH, HUD, and CDC funded 565 health and housing projects combined. The Neighborhood pathway was most common, followed by studies of the Safety and Quality pathway. Studies of the Affordability and Stability pathways were least common. Health topics such as substance use, mental health, and cardiovascular disease were most often studied. Most studies were observational (66%); only a little over one fourth (27%) were intervention studies. This review of the research grant portfolios of three major federal funders of health and housing research in the United States describes the diversity and substantial investment in research at the intersection between housing and health. Analysis of the combined portfolio points to gaps in studies on causal pathways linking housing to health outcomes. The findings highlight the need for research to better understand the causal pathways from housing to health and prevention intervention research, including rigorous evaluation of housing interventions and policies to improve health and well-being.

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) <3.5x109/L or a neutrophil count <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 <2.5x109/L or neutrophil count <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.

Evaluating Funding for Authors Achieving High Citations vs. Online Popularity.

The Altmetric score is a validated tool that measures online attention of scientific studies. A relationship between government/industry funding for authors and their study's citations have been previously demonstrated. It is not known whether funding is related to greater online attention. We hypothesize authors publishing studies achieving greater online attention (higher Altmetric scores) receive greater monetary support from industry while authors publishing studies achieving critical acclaim (more citations) receive greater monetary support from the National Institute of Health (NIH). Top spine surgery studies between 2010 and 2021 were selected based on Altmetric scores and citation number. The Open Payments Database was accessed to evaluate industry financial relationships while the NIH Research Portfolio Online Reporting Tool was accessed to evaluate NIH funding. Payments were compared between groups and analyzed with the Student t-test, analysis of variance, and chi square analysis. Alpha <0.05. There were 60 and 51 authors with payment data in the top 50 Altmetric and top 50 citation studies, respectively, with eight authors having studies in both groups. Total industry payments between groups were not markedly different. The eight authors with studies in both groups received markedly more industry payments for consulting, travel/lodging, and faculty/speaking fees. Authors with articles in both groups (50%) were significantly more likely to receive NIH support, compared with authors of the top Altmetric articles (5%; P < 0.001) and top citation articles (12%; P < 0.001). Authors receiving NIH support received significantly less industry payments compared with authors not receiving NIH support ($148,544 versus $2,159,526; P < 0.001). These findings reject our hypothesis: no notable differences for industry payments and NIH funding between authors for top Altmetric and citation studies. Authors receiving funding from industry versus the NIH are generally two distinct groups, but there is a small group supported by both. These studies achieve both critical acclaim (citations) and online popularity (Altmetric scores). Data can be available on reasonable request.

Funding for Refugee Health Research From the National Institutes of Health Between 2000 and 2020

The US has historically resettled more refugees than any other country, with over 3.5 million refugees since 1980. The National Institutes of Health (NIH) is the largest public funder of biomedical research and development, but its role in mitigating many health disparities refugees experience through its funded research remains unknown. To examine the NIH's research funding patterns on refugee health research over the last 2 decades. Secondary analysis of NIH-funded grants between 2000 and 2020 using a cross-sectional study design. The NIH Research Portfolio Online Reporting Tools database was used to find relevant grants. Data were analyzed from November 2021 to September 2022. NIH grants awarded by year, state, grant type, research area, funding institute, grant duration, and amount funded. Of 1.7 million NIH grants funded over the 20-year study period, only 78 addressed refugee health. Funded grants were mostly training grants (23 grants [29%]), followed by hypothesis-driven research (R01 grants; 22 grants [28%]), pilot or preliminary investigation proposals (13 grants [17%]), and other types of grants (20 grants [26%]). The most studied research domain was mental health (36 grants [46%]), followed by refugee family dynamics and women's and children's health (14 grants [18%]). A total of 26 grants (33%) were funded by the National Institute of Mental Health and 15 (19%) were funded by the National Institute of Child Health and Human Development. Most grants were US-based (60 grants [76%]) and the state of Massachusetts received the greatest amount of funding ($14 825 852 [18%]). In 2020, the NIH allocated about $2.3 million to refugee health research, or less than 0.01% of its $42 billion budget that year. The number of grants funded in each time period did not always reflect changes in the number of refugees resettled in the US over the years. This cross-sectional study found that there remain significant gaps in the understanding of and interventions in the health research needs of refugees locally and along the migratory route. To close these gaps, the NIH should increase its investments in comprehensive studies assessing the physical, mental, and social well-being of this expanding population. This can be achieved by ensuring that all NIH institutes allocate budgets specifically for refugee health research and extend support for the training of refugee researchers.

Towards stratified treatment of JIA: machine learning identifies subtypes in response to methotrexate from four UK cohorts

Methotrexate (MTX) is the gold-standard first-line disease-modifying anti-rheumatic drug for juvenile idiopathic arthritis (JIA), despite only being either effective or tolerated in half of children and young people (CYP). To facilitate stratified treatment of early JIA, novel methods in machine learning were used to i) identify clusters with distinct disease patterns following MTX initiation; ii) predict cluster membership; and iii) compare clusters to existing treatment response measures. Discovery and verification cohorts included CYP who first initiated MTX before January 2018 in one of four UK multicentre prospective cohorts of JIA within the CLUSTER consortium. JADAS components (active joint count, physician (PGA) and parental (PGE) global assessments, ESR) were recorded at MTX start and over the following year. Clusters of MTX 'response' were uncovered using multivariate group-based trajectory modelling separately in discovery and verification cohorts. Clusters were compared descriptively to ACR Pedi 30/90 scores, and multivariate logistic regression models predicted cluster-group assignment. The discovery cohorts included 657 CYP and verification cohorts 1241 CYP. Six clusters were identified: Fast improvers (11%), Slow Improvers (16%), Improve-Relapse (7%), Persistent Disease (44%), Persistent PGA (8%) and Persistent PGE (13%), the latter two characterised by improvement in all features except one. Factors associated with clusters included ethnicity, ILAR category, age, PGE, and ESR scores at MTX start, with predictive model area under the curve values of 0.65-0.71. Singular ACR Pedi 30/90 scores at 6 and 12 months could not capture speeds of improvement, relapsing courses or diverging disease patterns. Six distinct patterns following initiation of MTX have been identified using methods in artificial intelligence. These clusters demonstrate the limitations in traditional yes/no treatment response assessment (e.g., ACRPedi30) and can form the basis of a stratified medicine programme in early JIA. Medical Research Council, Versus Arthritis, Great Ormond Street Hospital Children's Charity, Olivia's Vision, and the National Institute for Health Research.

The FraiLTI (Frailty in chronic Limb-Threatening Ischaemia) Protocol

Background: Frailty, sarcopenia and multimorbidity are conditions commonly associated with the ageing process, and they are frequently observed in patients with chronic limb-threatening ischaemia (CLTI). Nevertheless, the extent to which these conditions are prevalent within the CLTI patient population has not been adequately examined in the UK. This proposed multicentre observational study aims to investigate the prevalence of these conditions in patients with CLTI and to assess their potential impact on important clinical outcomes including mortality, amputation and quality of life. Methods: FraiLTI (Frailty in chronic Limb-Threatening Ischaemia) is a multicentre prospective observational study in the UK that that aims to investigate the prevalence of frailty, sarcopenia and multimorbidity associated with CLTI. The secondary objective is to investigate potential correlations between frailty, sarcopenia and multimorbidity, with clinical outcomes such as amputation, mortality, major adverse cardiovascular events and readmission rates within a 90-day period. FraiLTI is led by Newcastle University, supported by the Vascular and Endovascular Research Network (VERN) and funded by the National Institute for Health Research (NIHR) and the Newcastle Hospital Charities. REDCap will be used to collect anonymised patient data. All hospitals with a dedicated vascular centre are eligible to participate. Full ethical approval (21/PR/0750) was granted on 13 July 2021. The study is registered on the International Standard Randomised Controlled Trial Number (ISRCTN) registry. Anticipated impact of the study: This study has the potential to address critical questions identified by the James–Lind Alliance (JLA) Priority Setting Partnership (PSP) in peripheral arterial disease. It is expected to make a substantial contribution to the creation of a prospective CLTI database, integrating essential data on frailty, sarcopenia and multimorbidity that are not currently captured by other registries, despite their profound impact on patient outcomes. This research could provide pivotal insights into the prevalence of frailty, sarcopenia and multimorbidity among the UK’s CLTI population and their corresponding effects on clinical outcomes. Findings from the study will be shared at global scientific conferences and submitted to be published in peer-reviewed journals.

Musculoskeletal health: an ecological study assessing disease burden and research funding

Exacerbated by an aging population, musculoskeletal diseases are a chronic and growing problem in the United States that impose significant health and economic burdens. The objective of this study was to analyze the correlation between the burden of diseases and the federal funds assigned to health-related research through the National Institutes of Health (NIH). An ecological study design was used to examine the relationship between NIH research funding and disease burden for 60 disease categories. We used the Global Burden of Disease (GBD) Study 2019 to measure disease burden and the NIH Research, Condition, and Disease Categories (RCDC) data to identify 60 disease categories aligned with available GBD data. NIH funding data was obtained from the RCDC system and the NIH Office of Budget. Using linear regression models, we observed that musculoskeletal diseases were among the most underfunded (i.e., negative residuals from the model) with respect to disease burden. Musculoskeletal diseases were underfunded, with neck pain being the most underfunded at only 0.83% of expected funding. Low back pain, osteoarthritis, and rheumatoid arthritis were also underfunded at 13.88%, 35.08%, and 66.26%, respectively. Musculoskeletal diseases were the leading cause of years lived with disability and the third leading cause in terms of prevalence and disability-adjusted life years. Despite the increasing burden of these diseases, the allocation of NIH funding to the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) has remained low compared to other institutes. Despite the increasing health burden and economic cost of $980 billion annually, the allocation of NIH funding to the NIAMS has remained low compared to other institutes. These findings suggest that the NIH may need to reassess its allocation of research funding to align with the current health challenges of our country. Furthermore, these clinically relevant observations highlight the need to increase research funding for musculoskeletal diseases and improve their prevention, diagnosis, and treatment. No funding.

Chemoprevention for malaria with monthly intermittent preventive treatment with dihydroartemisinin–piperaquine in pregnant women living with HIV on daily co-trimoxazole in Kenya and Malawi: a randomised, double-blind, placebo-controlled trial

The efficacy of daily co-trimoxazole, an antifolate used for malaria chemoprevention in pregnant women living with HIV, is threatened by cross-resistance of Plasmodium falciparum to the antifolate sulfadoxine-pyrimethamine. We assessed whether addition of monthly dihydroartemisinin-piperaquine to daily co-trimoxazole is more effective at preventing malaria infection than monthly placebo plus daily co-trimoxazole in pregnant women living with HIV. We did an individually randomised, two-arm, placebo-controlled trial in areas with high-grade sulfadoxine-pyrimethamine resistance in Kenya and Malawi. Pregnant women living with HIV on dolutegravir-based combination antiretroviral therapy (cART) who had singleton pregnancies between 16 weeks' and 28 weeks' gestation were randomly assigned (1:1) by computer-generated block randomisation, stratified by site and HIV status (known positive vs newly diagnosed), to daily co-trimoxazole plus monthly dihydroartemisinin-piperaquine (three tablets of 40 mg dihydroartemisinin and 320 mg piperaquine given daily for 3 days) or daily co-trimoxazole plus monthly placebo. Daily co-trimoxazole consisted of one tablet of 160 mg sulfamethoxazole and 800 mg trimethoprim. The primary endpoint was the incidence of Plasmodium infection detected in the peripheral (maternal) or placental (maternal) blood or tissue by PCR, microscopy, rapid diagnostic test, or placental histology (active infection) from 2 weeks after the first dose of dihydroartemisinin-piperaquine or placebo to delivery. Log-binomial regression was used for binary outcomes, and Poisson regression for count outcomes. The primary analysis was by modified intention to treat, consisting of all randomised eligible participants with primary endpoint data. The safety analysis included all women who received at least one dose of study drug. All investigators, laboratory staff, data analysts, and participants were masked to treatment assignment. This trial is registered with ClinicalTrials.gov, NCT04158713. From Nov 11, 2019, to Aug 3, 2021, 904 women were enrolled and randomly assigned to co-trimoxazole plus dihydroartemisinin-piperaquine (n=448) or co-trimoxazole plus placebo (n=456), of whom 895 (99%) contributed to the primary analysis (co-trimoxazole plus dihydroartemisinin-piperaquine, n=443; co-trimoxazole plus placebo, n=452). The cumulative risk of any malaria infection during pregnancy or delivery was lower in the co-trimoxazole plus dihydroartemisinin-piperaquine group than in the co-trimoxazole plus placebo group (31 [7%] of 443 women vs 70 [15%] of 452 women, risk ratio 0·45, 95% CI 0·30-0·67; p=0·0001). The incidence of any malaria infection during pregnancy or delivery was 25·4 per 100 person-years in the co-trimoxazole plus dihydroartemisinin-piperaquine group versus 77·3 per 100 person-years in the co-trimoxazole plus placebo group (incidence rate ratio 0·32, 95% CI 0·22-0·47, p<0·0001). The number needed to treat to avert one malaria infection per pregnancy was 7 (95% CI 5-10). The incidence of serious adverse events was similar between groups in mothers (17·7 per 100 person-years in the co-trimoxazole plus dihydroartemisinin-piperaquine group [23 events] vs 17·8 per 100 person-years in the co-trimoxazole group [25 events]) and infants (45·4 per 100 person-years [23 events] vs 40·2 per 100 person-years [21 events]). Nausea within the first 4 days after the start of treatment was reported by 29 (7%) of 446 women in the co-trimoxazole plus dihydroartemisinin-piperaquine group versus 12 (3%) of 445 women in the co-trimoxazole plus placebo group. The risk of adverse pregnancy outcomes did not differ between groups. Addition of monthly intermittent preventive treatment with dihydroartemisinin-piperaquine to the standard of care with daily unsupervised co-trimoxazole in areas of high antifolate resistance substantially improves malaria chemoprevention in pregnant women living with HIV on dolutegravir-based cART and should be considered for policy. European and Developing Countries Clinical Trials Partnership 2; UK Joint Global Health Trials Scheme (UK Foreign, Commonwealth and Development Office; Medical Research Council; National Institute for Health Research; Wellcome); and Swedish International Development Cooperation Agency.

Role of Epstein-Barr Virus in Breast Cancer: Correlation with Clinical Outcome and Survival Analysis.

Background: Breast cancer is the most prevalent cancer among women worldwide. The potential involvement of Epstein-Barr virus (EBV) in breast cancer pathogenesis has been a subject of debate, but its correlation with clinical outcomes remains uncertain. Methods: In this study, we collected 276 pathologically confirmed breast cancer tissue samples from the tissue bank of MacKay Memorial Hospital and the National Health Research Institutes in Taiwan. DNA was extracted from frozen tissue using The QIAamp DNA Mini Kit. The Taqman quantitative PCR method was employed to assess the EBV copy number per cell in these samples, using NAMALWA cells as a reference. We performed statistical analyses, including 2 × 2 contingency tables, Cox regression analysis, and Kaplan-Meier survival curves, to explore the association between clinicopathologic factors and survival outcomes in breast cancer patients. We analyzed both relapse survival, which reflects the period patients remain free from cancer recurrence post-treatment, and overall survival, which encompasses all-cause mortality. Results: Our results revealed a significant association between EBV status and relapse survival (hazard ratio: 2.75, 95% CI: 1.30, 5.86; p = 0.008) in breast cancer patients. However, no significant association was found in overall survival outcomes. Additionally, we observed significant associations between ER status and tumor histologic grade with both overall and relapse survival. Patients with EBV-positive tumors exhibited higher recurrence rates compared to those with EBV-negative tumors. Furthermore, we noted significant correlations between EBV status and HER-2 (p = 0.0005) and histological grade (p = 0.02) in our cohort of breast cancer patients. Conclusions: The presence of EBV in breast cancer tumors appears to exert an impact on patient outcomes, particularly concerning recurrence rates. Our findings highlight the significance of considering EBV status as a potential prognostic marker in breast cancer patients. Nonetheless, further research is essential to elucidate the underlying molecular mechanisms and develop novel therapeutic approaches.

Assessing the Relationship between Radiology Department Research Funding and Institutional Community Inclusion and Investment.

Background Health care access disparities and lack of inclusion in clinical research have been well documented for marginalized populations. However, few studies exist examining the research funding of institutions that serve historically underserved groups. Purpose To assess the relationship between research funding awarded to radiology departments by the National Institutes of Health (NIH) and Lown Institute Hospitals Index rankings for inclusivity and community benefit. Materials and Methods This retrospective study included radiology departments awarded funding from the NIH between 2017 and 2021. The 2021 Lown Institute Hospitals Index rankings for inclusivity and community benefit were examined. The inclusivity metric measures how similar a hospital's patient population is to the surrounding community in terms of income, race and ethnicity, and education level. The community benefit metric measures charity care spending, Medicaid as a proportion of patient revenue, and other community benefit spending. Linear regression and Pearson correlation coefficients (r values) were used to evaluate the relationship between aggregate NIH radiology department research funding and measures of inclusivity and community benefit. Results Seventy-five radiology departments that received NIH funding ranging from $195 000 to $216 879 079 were included. A negative correlation was observed between the amount of radiology department research funding received and institutional rankings for serving patients from racial and/or ethnic minorities (r = -0.34; P < .001), patients with low income (r = -0.44; P < .001), and patients with lower levels of education (r = -0.46; P < .001). No correlation was observed between the amount of radiology department research funding and institutional rankings for charity care spending (r = -0.19; P = .06), community investment (r = -0.04; P = .68), and Medicaid as a proportion of patient revenue (r = -0.10; P = .22). Conclusion Radiology departments that received more NIH research funding were less likely to serve patients from racial and/or ethnic minorities and patients who had low income or lower levels of education. © RSNA, 2024 See also the editorial by Mehta and Rosen in this issue.

Reimagined day care for older people - supporting older people and caregivers to age in place.

There is a widespread view amongst policy makers, as well as some senior managers and commissioners in local authorities, that collective forms of day care for older people are outdated and not aligned with wider policy ambitions. However, there is also growing recognition, amongst advocacy organisations such as Carers UK and Age UK, that many older people and their caregivers would welcome the opportunity to attend collective day care services, as well as growing interest amongst providers of services and older people themselves about the need to transform provision. &#x0D; As health and social care commissioners in England develop Integrated Care Systems, there is potential for reimagined day care for older people to play an important role in delivering person-centred, preventative and place-based care for older people and their caregivers, including enabling older people to live at home for longer as well as addressing wellbeing, loneliness and social isolation. &#x0D; The presentation will outline findings from case studies visited as part of a National Institute for Health Research, School for Social Care Research study exploring the experiences of and aspirations for collective day care in England, from the perspectives of older people, their carers, those who work in or manage services, as well as local stakeholders from the health and care system. For this research, day care is defined as community building-based services that provide care and/or health related services and/or clubs and activities specifically for older people (65+) with care and support needs. &#x0D; Case studies visited included a range of models of day care for older people including day centres for people living with dementia, small-scale day care based in a hosts home, to large-scale preventative provision for older people. The study explored: peoples experiences of attending; impact on wellbeing and health of older people and their caregivers; what an ideal model of day care would look like; experiences of day care through the COVID-19 pandemic; and relationships with local health and community partners. &#x0D; Our findings highlight the role day care can play in providing opportunities for connection and friendship for older people who attend, supporting caregivers to sustain their caring role, and supporting physical and mental wellbeing and health of older people and their caregivers. Highlighting the importance of personal connections, joy and purposeful activity, design of the physical space and connections with local place, the presentation will discuss innovations in practice that may support a ‘reimagining of day care’, ensuring it meets the aspirations of older people and their caregivers, as well as supporting wider policy ambitions including how social care services can contribute to the wider preventative health agenda. &#x0D;

How important is integration to the successful ‘roll out’ of specialist hospital discharge schemes for people who are homeless?

In 2021, we published research funded by the UK National Institute for Health Research that demonstrated the effectiveness and cost effectiveness of specialist hospital discharge schemes for people who are homeless. A key finding of the research was that areas that had a specialist homeless hospital discharge scheme had fewer delayed discharges and could reduce their emergency readmissions among homeless patients by 14%. This positive outcome attracted the attention of national health policy makers who allocated £16 million funding to 17 local authority areas to “roll out” new schemes. This paper reports the preliminary findings of an implementation evaluation. We assess how important integration was in those areas that successfully translated the evidence about “what works’ into practice. This presentation is targeted at academics and commissioners of integrated care.&#x0D; The evaluation employed a positive deviance (appreciative enquiry) methodology. This approach seeks out exceptionally performing sites, investigates the underlying factors contributing to the successful behaviours and strategies, and plans an appropriate means to replicate these with the aim to effect a change. The rationale behind appreciative inquiry is that solutions to common problems mostly exist within clinical/practice communities rather than externally with policy makers or managers.&#x0D; The first step of the evaluation was to collect audit (performance) data from the 17 local authorities taking part in the programme. Audit data was then used to select three case studies sites that demonstrated high performance against key metrics such as having a shorter length of stay in ‘step-down’ services (longer stays being indicative of housing shortages and difficulties maintaining flow through the system). In the case study sites, reflective interviews and focus groups then sought to establish what factors underpinned this successful implementation. This included interviews with a range of key stakeholders including people with lived experience of homelessness and transitions out-of-hospital (over sixty stakeholders in total).&#x0D; Integration was found to be a key factor in understanding successful implementation at many different levels - from building the initial strategic vision to delivering quality in frontline service delivery. Often this was ‘relational’ integration where building social networks in strategic places was the main factor in determining routinization and sustainability. Often boundary spanning was key where ‘homeless commissioners’ needed to cross the divide into the unfamiliar world of health service commissioning. Relational working required a dedicated project manager with highly developed skills in business planning, evaluation and policy literacy to negotiate the many hurdles that stood in the way of the routinization of specialist care. Successful sites also involved people with lived experience of homeless in meaningful rather than tokenistic activities, integrating their knowledge of services and practice to ensure compassion was at the forefront of practice. Taking an in-depth qualitative perspective on successful implementation is important as very few of the 17 test sites managed to sustain their new services once the initial programme funding had run out.&#x0D;