Recruitment Site Research Articles

A07 - EDI&S Outputs of appointing a Trainee Executive Group in delivering a multi-centre randomized controlled surgical trial: Lessons learnt from The Sunflower Study

Abstract Background Randomised controlled trials (RCTs) are widely accepted as the ‘gold standard’ for evaluating the effectiveness of health interventions. Trial recruitment is notoriously difficult, with approximately 57% of publicly funded RCTs not meeting recruitment target sample sizes. Trainee involvement can be crucial for large scale clinical studies. However, there remains limited knowledge about methods in which trainee collaboration can assist studies in achieving their aims. The Sunflower Study is the UKs largest surgical RCT and is unique in piloting the establishment of a Trainee Executive Group (TEG). Here we explore the outputs of the TEG and its impact on the study. Method The TEG consists of five trainee representatives of different training grades and research backgrounds, all appointed via national selection. The TEG held regular virtual meetings seeking to understand trainee perspectives on RCTs recruitment, champion and disseminate examples of good recruitment, indentify recruitment barriers, optimise The Sunflower Study's social media presence and update digital resources via a trainee section on its website. The TEG also established a network of regional representatives with the purpose of connecting neighbouring recruitment sites with one another, disseminating knowledge at a local level, sharing recruitment tips and encouraging local/national competition. All of these strategies aimed to ultimately boost patient recruitment. Results The regional representative network assisted with setting up a new recruitment site, who have since remained a top recruiter. The TEGs establishment saw the highest number of trainees attend the study's yearly ‘Investigators' Meeting’. The TEGs engagement with the study’s social media led to an increase in follower numbers and consistently maintained high tweet impressions. The Sunflower Study is affiliated with the NIHR API scheme and has 165 collaborators registered with the scheme - the highest of any UK study. Through this, trainees are able to develop leadership, communication and research skills; as well as gain competencies required for CCT. Conclusion The implementation of the TEG illustrates how innovative strategies can be utilised to actively involve trainees in research. Following the establishment of the TEG, new sites participated in the study, the study's social media impact increased and trainee engagement was optimised. The TEG also encouraged trainees' future involvement with research through the API scheme. In the post-COVID-19 era, collaborative studies have proven their role in providing high impact quality research. Future studies could foster the TEG model, with an appointed trainee leadership team focusing on maximising trainee output, providing benefits not only for the trainees themselves, but also recruitment sites and studies overall.

“Ask” or “Inquire”: operationalizing speech formality in psychosis and its risk states using etymology

Many individuals with psychotic symptoms have less complex language than healthy individuals. Word etymology is a lexical feature that has not yet been studied in clinical populations, but among healthy individuals, words of Old French origin are chosen over Germanic-origin words to convey formality (e.g. “inquire” vs. “ask”). Differences in language complexity among individuals with psychotic symptoms may relate to differences in etymological content in speech. Here, we determined the proportion of Germanic-origin word use and Old-French-origin word use in a large cohort of individuals with recent-onset psychosis or at clinically high risk for psychosis, hypothesizing that individuals with recent onset psychosis would have increased use of Germanic-origin words and decreased use of Old-French-origin words. This hypothesis was borne out, even after adjusting for sex, age, recruitment site, education, racial identity, and for a subset, IQ. Etymology proportions were associated with role but not social functioning in individuals with psychotic symptoms, consistent with the premise that they reflect speech formality. Understanding speech differences in the psychosis spectrum through the lens of etymology may lead to new interventions to improve role functioning.

How to make cardiology clinical trials more inclusive.

Cardiovascular clinical trials continue to under-represent children, older adults, females and people from ethnic minority groups relative to population disease distribution. Here we describe strategies to foster trial representativeness, with proposed actions at the levels of trial funding, design, conduct and dissemination. In particular, trial representativeness may be increased through broad recruitment strategies and site selection criteria that reflect the diversity of patients in the catchment area, as well as limiting unjustified exclusion criteria and using pragmatic designs that minimize research burden on patients (including embedded and decentralized trials). Trial communications ought to be culturally appropriate; engaging diverse people with lived experience in the co-design of some trial elements may foster this. The demographics of trialists themselves are associated with participant demographics; therefore, trial leadership must be actively diversified. Funding bodies and journals increasingly require the reporting of sociodemographic characteristics of trial participants, and regulatory bodies now provide guidance on increasing trial diversity; these steps may increase the momentum towards change. Although this Perspective focuses on the cardiovascular trial context, many of these strategies could be applied to other fields.

High-load strength training compared with standard care treatment in young adults with joint hypermobility and knee pain: study protocol for a randomised controlled trial (the HIPEr-Knee study)

IntroductionPatients with generalised joint hypermobility, including knee hypermobility (GJHk), often experience knee pain and are typically managed with low-intensity strength training and/or proprioceptive training as part of standard care. However,...

Using publicly available UK datasets to identify recruitment sites to maximise inclusion of under-served groups: three case studies

Background There is strong evidence that those recruited into studies are not always representative of the population for whom the research is most relevant. Development of the study design and funding decisions are points in the research process where considerations about inclusion of under-served populations may usefully be made. Current practical guidance focuses on designing and modifying participant recruitment and retention approaches but an area that has not been addressed is recruitment site selection. Methods We present case studies of three NIHR funded trials to demonstrate how publicly available UK population datasets can be used to facilitate the identification of under-served communities for inclusion in trials. The trials have different designs, address different needs and demonstrate recruitment planning across Trauma centres, NHS Trusts and special educational settings. We describe our use of national freely available datasets, such as those provided by NHS Digital and the Office for National Statistics, to identify potential recruitment sites with consideration of health status, socio-economic status and ethnicity as well as clinical and risk factors to support inclusivity. For all three studies, we produced lists of potential recruitment sites in excess of the number anticipated as necessary to meet the recruitment targets. Discussion We reflect on the challenges to our approach and some potential future developments. The datasets used are all free to use but each has their limitations. Agreeing search parameters, acceptable proxies and identifying the appropriate datasets, then cross referencing between datasets takes considerable time and particular expertise. The case studies are trials, but the methods are generalisable for various other study types. Conclusion Through these exemplars, we aim to build on the NIHR INCLUDE project, by providing trialists with a much needed practical approach to embedding EDI into trial design at the grant application stage.

Long range regulation of transcription scales with genomic distance in a gene specific manner.

While critical for tuning the timing and level of transcription, enhancer communication with distal promoters is not well understood. Here we bypass the need for sequence-specific transcription factors and recruit activators directly using CARGO-VPR, an approach for targeting dCas9-VPR using a multiplexed array of RNA guides. We show that this approach achieves effective activator recruitment to arbitrary genomic sites, even those inaccessible by single dCas9. We utilize CARGO-VPR across the Prdm8-Fgf5 locus in mESCs, where neither gene is expressed. We demonstrate that while activator recruitment to any tested region results in transcriptional induction of at least one gene, the expression level strongly depends on the genomic distance between the promoter and activator recruitment site. However, the expression-distance relationship for each gene scales distinctly in a manner not attributable to differences in 3D contact frequency, promoter DNA sequence or presence of the repressive chromatin marks at the locus.

Neonatal BCG Vaccination for Prevention of Allergy in Infants: The MIS BAIR Randomised Controlled Trial.

The beneficial off-target effects of Bacille Calmette-Guérin (BCG) vaccination potentially include protection against allergy. In the MIS BAIR trial, we aimed to determine whether neonatal BCG vaccination reduces atopic sensitisation and clinical food allergy in infants. In this randomised controlled trial, 1272 neonates were allocated to BCG-Denmark vaccine (0.05 mL intradermal dose) or no BCG at birth. Randomisation was stratified by recruitment site, mode of delivery and plurality of birth. The primary outcome was the incidence of atopic sensitisation determined by skin prick test at 1 year of age. Food allergy was determined by 3-monthly online questionnaires and oral food challenges. Data were analysed by intention-to-treat using binary regression. gov (NCT01906853). Atopic sensitisation during the first year of life was 22.9% among infants in the BCG group and 18.9% in the control group (adjusted risk difference (aRD) 3.8% (95% CI -1.5 to 9.1) after multiple imputation). Clinical food allergy was similar between infants in the BCG and control groups (9.8% vs. 9.6%; aRD 0.2, 95% CI -3.4 to 3.8). An interaction was observed between the primary outcome and maternal history of BCG vaccination. No interaction was observed for the additional prespecified potential effect modifiers tested (sex, delivery mode, family history of any allergy, season of birth, hepatitis B vaccination at randomisation, BCG scar and age at BCG administration). Neonatal BCG-Denmark vaccination does not protect against atopic sensitisation or clinical food allergy in the first year of life.

Predictors of subacute postoperative pain after total knee arthroplasty: A secondary analysis of two randomized trials.

Methods for identifying high-pain responders undergoing total knee arthroplasty remain important to improve individualized pain management. This study aimed at evaluating pre- and perioperative predictors of pain on Days 2-7 after total knee arthroplasty. This is a secondary analysis of data from 227 patients participating in two randomized trials. Pain outcomes were mean pain during walking on Days 2-7 and on Days 2, 4 and 7. Multivariable linear and logistic regressions were carried out in two steps. First, only preoperative available variables including demographics, comorbidities, pain catastrophizing scale and preoperative pain were evaluated while controlling for trial intervention and recruitment site. In the second step, perioperative variables and pain during walking 24 h postoperatively were added. The model with only preoperative predictors for mean pain Days 2-7 showed preoperative pain (R-squared 0.097) as the only predictor. In the second model, adding postoperative available variables, only pain 24 h postoperatively (R-squared 0.248) was significant, with a significant main effect of recruitment site. Results for the separate day analysis similarly showed preoperative pain and pain during walking 24 h postoperatively as predictors. The overall best sensitivity (60%) and specificity (74%) for predicting a high-subacute postoperative pain response on Days 2-7 was with cut-off values of VAS 45.5 (out of 100) for pain during walking 24 h postoperatively. Postoperative pain during walking at 24 h is predictive of subacute postoperative pain on Days 2-7 after total knee arthroplasty, while preoperative pain was only a weak predictor. This study investigated factors associated with pain after total knee arthroplasty beyond the immediate postoperative period. The analysis revealed significant associations between preoperative pain levels and, particularly, pain 24 h postoperatively, with subsequent subacute pain the following week. These findings can assist in identifying patients who would benefit from enhanced, individualized analgesic interventions to facilitate postoperative recovery.

Acceptability and perceived benefits of validated pruritus assessment instruments in the dermatological office and clinic: Theperspectives of patients and physicians.

Several patient-reported outcome measures (PROMs) have been developed for research to assess the multiple dimensions of chronic pruritus (CP). The acceptability and perceived benefits of their use in clinical practice remain unknown. To assess the acceptability and perceived benefits of validated PROMs from the perspective of patients and physicians in dermatological offices and clinics. Patients with CP due to atopic dermatitis, psoriasis, chronic prurigo or chronic urticaria were recruited at 10 dermatological offices and two dermatological clinics in Germany. Patients completed a set of validated PROMs on pruritus intensity (numerical rating scale, NRS), symptom control (itch-controlled days, ItchCD), quality of life (Dermatology Life Quality Index, DLQI; 5-pruritus life quality, 5PLQ) and general health status (EuroQol, EQ-VAS). Acceptability (relevance, difficulty of completion, length) and benefits (usefulness, feasibility) of these tools were assessed on a NRS (0-10) by patients and physicians, respectively. Data were analysed descriptively. Linear regression was used to study potential associations between age, sex, occupation, office versus clinic, change of therapy and physician-reported benefits. N = 523 patients (46% male, average age: 53.5 years) participated. Acceptability of PROMs by patients was high, indicated by low difficulty (Md = 0, IQR = 0-1 for all PROMs) and high relevance (Md = 8, IQR = 4-10 for all PROMs). Also, most patients (89-95%) rated length of the questionnaires as 'exactly right'. Physicians rated the NRS as the most beneficial instrument (feasibility: Md = 8, IQR = 6-10; usefulness: Md = 9, IQR = 7-10). Hierarchical linear regression revealed that only recruitment site (dermatological office vs. clinic) was significantly associated with usefulness and feasibility (higher ratings for clinical context; βs = 0.149-0.258, ps <0.05; except feasibility for EQ5d, β = ns). PROMs are welcomed by patients, while physicians consider instruments measuring pruritus intensity and impairment of quality of life as beneficial for the clinical routine. Widespread implementation of PROMs in daily clinical work is needed to improve care.

A Biparatopic Intrabody Renders Vero Cells Impervious to Ricin Intoxication.

Expression of camelid-derived, single-domain antibodies (VHHs) within the cytoplasm of mammalian cells as "intrabodies" has opened-up novel avenues for medical countermeasures against fast-acting biothreat agents. In this report, we describe a heterodimeric intrabody that renders Vero cells virtually impervious to ricin toxin (RT), a potent Category B ribosome-inactivating protein (RIP). The intrabody consists of two structurally defined VHHs that target distinct epitopes on RT's enzymatic subunit (RTA): V9E1 targets RTA's P-stalk recruitment site, and V2A11 targets RTA's active site. Resistance to RT conferred by the biparatopic VHH construct far exceeded that of either of the VHHs alone and effectively inhibited all measurable RT-induced cytotoxicty in vitro. We propose that targeted delivery of bispecific intrabodies to lung tissues may represent a novel means to shield the airways from the effects of inhalational RT exposure.

Using patient portals for large-scale recruitment of individuals underrepresented in biomedical research: an evaluation of engagement patterns throughout the patient portal recruitment process at a single site within the All of Us Research Program.

To evaluate the use of patient portal messaging to recruit individuals historically underrepresented in biomedical research (UBR) to the All of Us Research Program (AoURP) at a single recruitment site. Patient portal-based recruitment was implemented at Columbia University Irving Medical Center. Patient engagement was assessed using patient's electronic health record (EHR) at four recruitment stages: Consenting to be contacted, opening messages, responding to messages, and showing interest in participating. Demographic and socioeconomic data were also collected from patient's EHR and univariate logistic regression analyses were conducted to assess patient engagement. Between October 2022 and November 2023, a total of 59592 patients received patient portal messages inviting them to join the AoURP. Among them, 24445 (41.0%) opened the message, 8983 (15.1%) responded, and 3765 (6.3%) showed interest in joining the program. Though we were unable to link enrollment data with EHR data, we estimate about 2% of patients contacted ultimately enrolled in the AoURP. Patients from underrepresented race and ethnicity communities had lower odds of consenting to be contacted and opening messages, but higher odds of showing interest after responding. Patient portal messaging provided both patients and recruitment staff with a more efficient approach to outreach, but patterns of engagement varied across UBR groups. Patient portal-based recruitment enables researchers to contact a substantial number of participants from diverse communities. However, more effort is needed to improve engagement from underrepresented racial and ethnic groups at the early stages of the recruitment process.

Faecal volatile organic compounds differ according to inflammatory bowel disease sub-type, severity, and response to treatment in paediatric patients.

Faecal volatile organic compounds (VOCs) differ with disease sub-type and activity in adults with established inflammatory bowel disease (IBD) taking therapy. To describe patterns of faecal VOCs in children newly presented with IBD according to disease sub-type, severity, and response to treatment. Children presenting with suspected IBD were recruited from three UK hospitals. Children in whom IBD was diagnosed were matched with a non-IBD child for age, sex, and recruitment site. Faecal VOCs were characterised by gas chromatography-mass spectrometry at presentation and 3months later in children with IBD. In 132 case/control pairs, median (inter-quartile range) age in IBD was 13.3years (10.2-14.7) and 38.6% were female. Compared with controls, the mean abundance of 27/62 (43.6%) faecal VOCs was statistically significantly decreased in Crohn's disease (CD), ulcerative colitis (UC) or both especially amongst ketones/diketones, fatty acids, and alcohols (p<0.05). Short-chain, medium chain, and branched chain fatty acids were markedly reduced in severe colitis (p<0.05). Despite clinical improvement in many children with IBD, the number and abundance of almost all VOCs did not increase following treatment, suggesting persistent dysbiosis. Oct-1-en-3-ol was increased in CD (p=0.001) and UC (p=0.012) compared with controls and decreased following treatment in UC (p=0.01). In CD, propan-1-ol was significantly greater than controls (p<0.001) and extensive colitis (p=0.001) and fell with treatment (p=0.05). Phenol was significantly greater in CD (p<0.001) and fell with treatment in both CD (p=0.02) and UC (p=0.01). Characterisation of faecal VOCs in an inception cohort of children with IBD reveals patterns associated with diagnosis, disease activity, and extent. Further work should investigate the relationship between VOCs and the microbiome in IBD and their role in diagnosis and disease monitoring.

Prevalence and trends of Chlamydia trachomatis infection in female sex workers and men who have sex with men in China: a systematic review and meta-analysis

IntroductionChlamydia trachomatis infection can cause a significant disease burden in high-risk populations. This study aimed to assess the overall prevalence of C. trachomatis infection, and determine the long-term trends and geographic distribution of this infection among female sex workers (FSWs) and men who have sex with men (MSM) in China.MethodsThe PubMed, Web of Science, CNKI, Wanfang Data and VIP databases were searched from 1 January 1990 through 30 April 2023. Publications in which C. trachomatis infection was detected using nucleic acid amplification tests (NAATs) were included. The Q test and I2 statistics were used to assess the heterogeneity between studies. A random-effect model was used to estimate the pooled prevalence of C. trachomatis infection. Subgroup, meta-regression, and sensitivity analyses were performed to explore the sources of heterogeneity. Publication bias was evaluated using Egger’s test. Trend analysis of the prevalence was performed using the Jonckheere-Terpstra trend test method.ResultsSixty-one studies were eligible for inclusion (including 38 for FSWs and 23 for MSM). The pooled prevalence of C. trachomatis infection was 19.5% (95% CI: 16.4, 23.0) among FSWs and 12.7% (95% CI: 9.2, 17.7) in the rectum, 6.4% (95% CI: 5.3, 7.8) in the urethra and 1.3% (95% CI: 0.8, 2.1) in the oropharynx from MSM in China. The subgroup analyses showed that the sample size, study period, study region, specimen collection type, molecular diagnosis method, and recruitment site could explain some heterogeneity among studies of FSWs, and the publication language, study period, study region, molecular diagnosis method, and specimen collection anatomical site could explain some heterogeneity among studies of MSM. From 1998 to 2004, 2005 to 2009, 2010 to 2015, and 2016 to 2021, the pooled prevalence of C. trachomatis infection among FSWs were 30.3%, 19.9%, 21.4%, and 11.3%, respectively. For MSM, the pooled prevalence from 2003 to 2009, 2010 to 2015, and 2016 to 2022 were 7.8%, 4.7%, and 6.5%, respectively. However, no overall decline in the prevalence of C. trachomatis infection was observed among FSWs (z = -1.51, P = 0.13) or MSM (z = -0.71, P = 0.48) in China.ConclusionsThe prevalence of C. trachomatis infection was high in these two high-risk populations in China. The findings of this study provide evidence for the formulation of effective surveillance and screening strategies for the prevention and control of C. trachomatis infection among these two specific populations.

#1450 Polygenic risk score of native IgA nephropathy predicts risk of post-transplant disease recurrence

Abstract Background and Aims IgA nephropathy (IgAN) is a polygenic immune-mediated progressive glomerular disease. Recent GWAS reported that high genome-wide polygenic risk score (IgAN GPS), including 1 249 077 variants mapping to systemic immune pathways, was associated with risk of end stage kidney disease (ESKD). Post transplant (KTx) IgAN recurrence occurs in 30% of cases and it is a major cause of graft loss. Pathogenesis and predictors of IgAN recurrence are still not well defined. Herein, we studied the role of native IgAN GPS and clinical factors in predicting post-KTx IgAN recurrence and graft failure in a large cohort of KTx recipients. Method Four thousand one hundred eighty six KTx recipients from 6 sites were genome wide genotyped and imputed against multi-ancestry reference panels, retrieving &amp;gt;10 million variants. In each recipient, native IgAN GPS was computed and standard-normalized (i.e. expressed in units of standard deviations from the mean distribution in matched controls). Native kidney disease diagnosis, clinical parameters, and post-KTx outcome data were retrieved retrospectively from clinical charts. The IgAN GPS was tested as predictor of native IgAN in the entire KTx cohort in a logistic regression model adjusted for sex, age, recruitment site, and first 5 PCs. IgAN GPS was tested as predictor of age at transplantation (proxy for age at ESKD) among KTx recipients with native IgAN in a linear regression model adjusted for sex, recruitment site, and first 5 PCs. In recipients with native IgAN, recipient and donor parameters were individually tested as predictors for time to IgAN recurrence and time to graft failure in Cox proportional hazards models adjusted for recruitment site and first 5 PCs. Predictors with P-value &amp;lt; .1 were included in the multivariable models. Recipient IgAN GPS was added to the clinical models and tested for prediction of time-to IgAN recurrence, and, among KTx recipients with IgAN recurrence, of time-to subsequent graft failure. Results Three hundred sixty nine KTx recipients were affected by native IgAN, 271 were of male sex, median age at transplantation was 45 years, and 149 received a living donor KTx. Over a median follow-up time of 46 months, 96 IgAN recurrence events occurred, and, among KTx recipients with recurrent IgAN, 27 subsequent graft failure events occurred after 100 months post KTx. IgAN GPS significantly predicted native IgAN cases among all KTx recipients (OR [95% CI]: 1.95 [1.76,2.16], p = 5.60E-07, AUROC 0.73), and lower age at transplantation among recipients with native IgAN (beta [s.e.]: −1.11[0.55], p = 0.04). Clinical model for IgAN recurrence included age, sex, year of transplant, HLA mismatch, recruitment site, and first 5 PCs; clinical model for graft failure included age, sex, year of transplant, HLA mismatch, type of donation, donor age, sex, rejection events, recruitment site, and first 5 PCs. At the multivariable analysis, IgAN GPS, lower age at transplantation, lower HLA mismatch, and higher year of transplant were independently associated with time to IgAN recurrence (Fig. 1a). Among KTx recipients with recurrent IgAN, higher IgAN GPS predicted time-to graft failure independently from clinical factors (Fig. 1b), but not in non-recurrent cases. Conclusion In the KTx setting, IgAN GPS was an independent predictor of IgAN recurrence, suggesting shared genetic susceptibility between native and recurrent IgAN. In addition, associations of IgAN GPS with lower age at transplantation, and with graft failure among recurrent IgAN cases, suggest that IgAN GPS may be predictive of a more aggressive native as well as recurrent disease. Associations with lower HLA mismatch advocate donor-recipient genetic similarities as potential additional predictors of IgAN recurrence. These data, which need external validation, may provide potential new insights into the pathobiology and prediction of recurrent IgAN.

Effectiveness of kangaroo mother care before clinical stabilisation versus standard care among neonates at five hospitals in Uganda (OMWaNA): a parallel-group, individually randomised controlled trial and economic evaluation

Preterm birth is the leading cause of death in children younger than 5 years worldwide. WHO recommends kangaroo mother care (KMC); however, its effects on mortality in sub-Saharan Africa and its relative costs remain unclear. We aimed to compare the effectiveness, safety, costs, and cost-effectiveness of KMC initiated before clinical stabilisation versus standard care in neonates weighing up to 2000 g. We conducted a parallel-group, individually randomised controlled trial in five hospitals across Uganda. Singleton or twin neonates aged younger than 48 h weighing 700-2000 g without life-threatening clinical instability were eligible for inclusion. We randomly assigned (1:1) neonates to either KMC initiated before stabilisation (intervention group) or standard care (control group) via a computer-generated random allocation sequence with permuted blocks of varying sizes, stratified by birthweight and recruitment site. Parents, caregivers, and health-care workers were unmasked to treatment allocation; however, the independent statistician who conducted the analyses was masked. After randomisation, neonates in the intervention group were placed prone and skin-to-skin on the caregiver's chest, secured with a KMC wrap. Neonates in the control group were cared for in an incubator or radiant heater, as per hospital practice; KMC was not initiated until stability criteria were met. The primary outcome was all-cause neonatal mortality at 7 days, analysed by intention to treat. The economic evaluation assessed incremental costs and cost-effectiveness from a disaggregated societal perspective. This trial is registered with ClinicalTrials.gov, NCT02811432. Between Oct 9, 2019, and July 31, 2022, 2221 neonates were randomly assigned: 1110 (50·0%) neonates to the intervention group and 1111 (50·0%) neonates to the control group. From randomisation to age 7 days, 81 (7·5%) of 1083 neonates in the intervention group and 83 (7·5%) of 1102 neonates in the control group died (adjusted relative risk [RR] 0·97 [95% CI 0·74-1·28]; p=0·85). From randomisation to 28 days, 119 (11·3%) of 1051 neonates in the intervention group and 134 (12·8%) of 1049 neonates in the control group died (RR 0·88 [0·71-1·09]; p=0·23). Even if policy makers place no value on averting neonatal deaths, the intervention would have 97% probability from the provider perspective and 84% probability from the societal perspective of being more cost-effective than standard care. KMC initiated before stabilisation did not reduce early neonatal mortality; however, it was cost-effective from the societal and provider perspectives compared with standard care. Additional investment in neonatal care is needed for increased impact, particularly in sub-Saharan Africa. Joint Global Health Trials scheme of the Department of Health and Social Care, Foreign, Commonwealth and Development Office, UKRI Medical Research Council, and Wellcome Trust; Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Coronavirus disease 2019 vaccination among young children: Associations with fathers’ and mothers’ influenza vaccination status

ObjectivesTo examine the association between parents’ influenza vaccination and their children’s coronavirus disease 2019 (COVID-19) vaccination status. MethodsParticipants included father-mother dyads from Fathers & Families, a cohort of fathers and their co-parents living in the United States. Parents’ influenza vaccination status and children’s COVID-19 vaccination status were reported from June 2022-July 2023. Logistic regression was used to examine the association between parental influenza vaccination (both parents vs. neither parent vs. mother only vs. father only vaccinated) and child COVID-19 vaccination (received at least 1 vs. 0 doses). Models were adjusted for recruitment site, income, parent education, child race/ethnicity, child age, and childcare enrollment. Inverse probability weighting was used to account for selection bias into the father-mother dyad sample. ResultsChildren were predominately non-Hispanic White (56 %) and aged 3–5 years (62 %). In most households, both parents (64 %) received the influenza vaccine and half (53 %) of children received the COVID-19 vaccine. One-in-four fathers (23 %) lacked knowledge about their child’s COVID-19 vaccination eligibility. Compared to children with two unvaccinated parents, having only their father (adjusted odds ratio [AOR] = 2.84, 95 % confidence interval [CI]: 1.52–5.36), only their mother (AOR = 4.04, 95 % CI: 2.16–7.68), and both parents (AOR = 10.33, 95 % CI: 6.29–17.53) vaccinated against influenza was associated with higher odds of children receiving the COVID-19 vaccine. ConclusionsFather and mother influenza vaccination is associated with child COVID-19 vaccination. Given many fathers were unaware their child was eligible for the COVID-19 vaccine, it is critical to tailor vaccine messaging for fathers.

Using publicly available UK datasets to identify recruitment sites to maximise inclusion of under-served groups: three case studies.

There is strong evidence that those recruited into studies are not always representative of the population for whom the research is most relevant. Development of the study design and funding decisions are points in the research process where considerations about inclusion of under-served populations may usefully be made. Current practical guidance focuses on designing and modifying participant recruitment and retention approaches but an area that has not been addressed is recruitment site selection. We present case studies of three NIHR funded trials to demonstrate how publicly available UK population datasets can be used to facilitate the identification of under-served communities for inclusion in trials. The trials have different designs, address different needs and demonstrate recruitment planning across Trauma centres, NHS Trusts and special educational settings.We describe our use of national freely available datasets, such as those provided by NHS Digital and the Office for National Statistics, to identify potential recruitment sites with consideration of health status, socio-economic status and ethnicity as well as clinical and risk factors to support inclusivity.For all three studies, we produced lists of potential recruitment sites in excess of the number anticipated as necessary to meet the recruitment targets. We reflect on the challenges to our approach and some potential future developments. The datasets used are all free to use but each has their limitations. Agreeing search parameters, acceptable proxies and identifying the appropriate datasets, then cross referencing between datasets takes considerable time and particular expertise. The case studies are trials, but the methods are generalisable for various other study types. Through these exemplars, we aim to build on the NIHR INCLUDE project, by providing trialists with a much needed practical approach to embedding EDI into trial design at the grant application stage.

Abstract 3460: Predicting cessation of immune checkpoint inhibitor therapy due to severe adverse events with an integrated autoimmune disease polygenic risk score

Abstract Background: Immune checkpoint inhibitors (ICIs), including anti-PD1/PD-L1 and anti-CTLA4 agents, have changed the landscape of cancer therapy. However, 6-30% of patients treated with ICIs can develop severe immune-related adverse events (irAEs) depending on the type of therapy used, often leading to cessation of treatment. Hundreds of genetic variants have been associated with autoimmune disorders, and recent genetic studies have developed polygenic risk scores (PRS) for composite risk of autoimmune disease (PRSAID). We used data from an ongoing observational study of patients with non-small cell lung cancer (NSCLC) treated with ICIs to evaluate the association between PRSAID and cessation of ICI therapy due to severe irAEs. Methods: Our cohort comprises 1,316 advanced NSCLC patients who received ICI therapy from four institutions between 2009 and 2022. Genotyping was performed using the Affymetrix Precision Medicine Array, and imputation was performed using 1000 Genomes Reference. To evaluate cessation of therapy due to severe irAEs, we conducted a thorough review of electronic health records. We identified permanent discontinuation of ICIs due to irAEs as cessation for at least 6 months without any disease progression. We tested the association of a previously published PRSAID (PMID: 35393596) with cessation of ICI due to any severe irAE. PRSAID was converted to a standard normal distribution. We conducted an unconditional logistic regression model to evaluate the association between a standardized PRSAID and discontinuation of ICI therapy due to severe irAEs. All models were adjusted for age at diagnosis, sex, type of ICI therapy, recruitment site, and 5 ancestry-informative principal components. Results: Of the 1,316 participants with genotype and outcome data, 171 (13.5%) of patients stopped ICI therapy due to severe irAEs. The most common irAEs leading to discontinuation were colitis, hepatitis, and pneumonitis. The PRSAID predicts the cessation of therapy due to severe irAEs with an odds ratio (OR) per standard deviation (SD) of 1.20 (95% confidence intervals [CI]=1.02-1.41, p=0.03). The association was stronger in individuals with high genetic risk (top 25th percentile compared to bottom 75th percentile of the PRSAID) (OR=1.60, 95% CI = 1.11-2.28, p=0.01). When we stratified the analysis by therapy type, we found an OR of 1.17 (95% CI-0.98-1.39, p = 0.08) for the anti-PD1/PD-L1 monotherapy groups and an OR of 1.48 (95% CI=0.94-2.40,p=0.09) for the dual anti-PD1/PD-L1 and anti-CTLA4 therapy group. Conclusions: An integrated PRS for autoimmunity can predict the cessation of ICI therapy due to severe irAEs in patients with advanced cancer. These findings suggest that PRS may help determine which patients may benefit from careful monitoring or even preventative measures for irAEs during ICI therapy. Citation Format: Pooja Middha, Rohit Thummalapalli, Zoe Quandt, Princess Margaret Lung Group, Matthew A. Gubens, Christine M. Lovly, Geoffrey Liu, Melinda C. Aldrich, Adam J. Schoenfeld, Elad Ziv. Predicting cessation of immune checkpoint inhibitor therapy due to severe adverse events with an integrated autoimmune disease polygenic risk score [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3460.

Abstract P470: The Virtual Home Clinic: Feasibility and Challenges for Longitudinal Cohorts

Longitudinal studies provide rich sources of data to explore early risk factors for future CV diseases. However, cohort participants often move away from their initial recruitment site. Our study assesses feasibility of mailing of devices to the home for collection of biometric data and user acceptability of this approach. Participants (N=308) from the Bogalusa Heart Study, National Growth &amp; Health Study and the Princeton Lipid Research Study who were initially enrolled as children in the 1970s and 1980s were recruited to conduct on-line surveys. A subset (N=74) had biometric measurement devices sent to the home ( Table ) for anthropometrics, BP, HR, heart rhythm, resting metabolic rate, O 2 saturation, glucose, total cholesterol, physical activity, diet, sleep duration/quality, and arterial stiffness. Stool and saliva were also collected for microbiome, and DNA. Of the 74 agreeing to participate in the home study, 62 (84%) successfully completed at least some testing. Among those 62, 72% of participants on average (range: 23% for AimStrip total cholesterol to 97% for Oragene) completed all requested readings for a given device. The total cholesterol test had the highest proportion of missing requested readings (45%). Of the 46 of 62 (74%) participants who completed the user acceptability survey, 28% preferred an in-clinic visit, 46% preferred home, and 26% did not have a preference. More males (63% vs 42% females) preferred home assessment. There was little difference between Black and White participants. On a scale of 1 (hard to use, poor directions, took too long) to 5 (easy to use, easy to follow directions, took little time), most devices scored near 4.5. The cholesterol test elicited the most negative responses, and several devices scored lower on the impression of the time it took to complete the at-home test. This feasibility study demonstrates that home biometric assessment is feasible and acceptable as we continue to follow our participants who have provided invaluable contributions to science for the last 40 years.

Assessment of Barriers to Referral and Appointment Wait Times for the Evaluation of Spinal Muscular Atrophy (SMA): Findings from a Web-Based Physician Survey.

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease characterized by progressive muscle weakness and atrophy. Clinical trial data suggest early diagnosis and treatment are critical. The purpose of this study was to evaluate neurology appointment wait times for newborn screening identified infants, pediatric cases mirroring SMA symptomatology, and cases in which SMA is suspected by the referring physician. Approaches for triaging and expediting referrals in the US were also explored. Cure SMA surveyed healthcare professionals from two cohorts: (1) providers affiliated with SMA care centers and (2) other neurologists, pediatric neurologists, and neuromuscular specialists. Surveys were distributed directly and via Medscape Education, respectively, between July 9, 2020, and August 31, 2020. Three hundred five total responses were obtained (9% from SMA care centers and 91% from the general recruitment sample). Diagnostic journeys were shorter for infants eventually diagnosed with SMA Type 1 if they were referred to SMA care centers versus general sample practices. Appointment wait times for infants exhibiting "hypotonia and motor delays" were significantly shorter at SMA care centers compared to general recruitment practices (p = 0.004). Furthermore, infants with SMA identified through newborn screening were also more likely to be seen sooner if referred to a SMA care center versus a general recruitment site. Lastly, the majority of both cohorts triaged incoming referrals. The average wait time for infants presenting at SMA care centers with "hypotonia and motor delay" was significantly shorter when initial referrals were triaged using a set of "key emergency words" (p = 0.036). Infants directly referred to a SMA care center versus a general sample practice were more likely to experience shorter SMA diagnostic journeys and appointment wait times. Triage guidelines for referrals specific to "hypotonia and motor delay" including use of "key emergency words" may shorten wait times and support early diagnosis and treatment of SMA.