A systematic review of symptoms experienced by children and young people with kidney failure.

BACKGROUND: Kidney failure at any age has a significant impact on quality of life (QoL) but the overall symptom burden for children and young people (CYP) is poorly described. Kidney failure has no cure and whilst transplantation is the preferred management option, it is not always possible, with patients requiring supportive care at the end of their lives. AIM: To use the literature to understand the symptom burden for CYP with kidney failure who are approaching end-of-life. METHODS: Using three databases, a systematic literature review was performed to identify eligible studies to extract data on symptoms experienced in CYP aged < 21 years with kidney failure. Data extraction was completed by two authors using a pre-designed proforma. Study quality assessment was undertaken using the BMJ AXIS tool. RESULTS: A total of 20,003 titles were screened to yielding 35 eligible studies including 2,862 CYP with chronic kidney disease (CKD), of whom 1,624 (57%) had CKD stage 5. The studies included a median of 30 (range 7-241) patients. Symptoms were subcategorised into eight groups: sleep, mental health, gastrointestinal, dermatology, ear, nose and throat (ENT), neurology, multiple symptoms, and ophthalmology. The prevalences of the most commonly reported symptoms were: restless leg syndrome 16.7-45%, sleep disordered breathing 20-46%, hypersomnia 14.3-60%, depression 12.5-67%, anxiety 5.3-34%, overall gastrointestinal symptoms 43-82.6%, nausea and vomiting 15.8-68.4%, abdominal pain 10.5-67.4%, altered appetite or anorexia 19-90%, xerosis 53.5-100%, pruritis 18.6-69%, headache 24-76.2% and ophthalmological symptoms 26%. Within each subgroup, the symptom definitions used were heterogeneous, the methods of assessment were varied and some symptoms, such as pain and constipation, were poorly represented. CONCLUSIONS: There is a marked lack of evidence relating to the symptom burden for CYP with CKD. This study highlights the high symptom prevalence, particularly in relation to sleep, mental health, headache, dermatological and gastrointestinal symptoms. There is a need for consensus recommendations on the evaluation and management of symptoms for CYP with CKD approaching end-of-life. PROSPERO ID: CRD42022346120.

The spectrum of co-existing disease in children with established kidney failure using registry and linked electronic health record data.

BACKGROUND: Children with established kidney failure may have additional medical conditions influencing kidney care and outcomes. This cross-sectional study aimed to examine the prevalence of co-existing diseases captured in the electronic hospital record compared to UK Renal Registry (UKRR) data and differences in coding. METHODS: The study population comprised children aged < 18 years receiving kidney replacement therapy (KRT) in England and Wales on 31/12/2016. Comorbidity data at KRT start was examined in the hospital record and compared to UKRR data. Agreement was assessed by the kappa statistic. Associations between patient and clinical factors and likelihood of coding were examined using multivariable logistic regression. RESULTS: A total of 869 children (62.5% male) had data linkage for inclusion. UKRR records generally reported a higher prevalence of co-existing disease than electronic health records; congenital, non-kidney disease was most commonly reported across both datasets. The highest sensitivity in the hospital record was seen for congenital heart disease (odds ratio (OR) 0.65, 95% confidence interval (CI) 0.51, 0.78) and malignancy (OR 0.63, 95% CI 0.41, 0.85). At best, moderate agreement (kappa ≥ 0.41) was seen between the datasets. Factors associated with higher odds of coding in hospital records included age, while kidney disease and a higher number of comorbidities were associated with lower odds of coding. CONCLUSIONS: Health records generally under-reported co-existing disease compared to registry data with fair-moderate agreement between datasets. Electronic health records offer a non-selective overview of co-existing disease facilitating audit and research, but registry processes are still required to capture paediatric-specific variables pertinent to kidney disease.

Mixed-methods research in nephrology.

Mixed-methods research involves the mixing of at least 1 qualitative and 1 quantitative method in the same research project or set of related projects. Combined use of qualitative and quantitative research methods in nephrology has increased over the last 10 years. In this review, we aim to advance the understanding of mixed-methods research within the kidney community. Qualitative and quantitative techniques provide different but noncompeting representations of what exists in the world; findings from qualitative research do not generalize to a large population, whereas those from quantitative research may not apply to individuals within the diverse and heterogeneous larger population. Mixed-methods research combines these complementary representations, allowing the strengths of each method to be combined and the strengths of 1 method to address the limitations of the other. Mixed-methods approaches can be used to: (i) gain a more complete understanding of a research problem, (ii) explain initial results from one method with results from another, (iii) generate instruments, for example, survey tools and interventions, (iv) evaluate services, and (v) optimize clinical trial design and delivery. There are 3 core mixed-methods designs: explanatory sequential, exploratory sequential, and convergent parallel, which can be combined. We discuss each design in turn before discussing analysis and integration of findings from the different methods. We provide case studies that illustrate the application of these study designs to kidney research questions. We briefly discuss mixed-methods systematic reviews and evidence synthesis before finally highlighting guidance on how to appraise published mixed-methods research.

Increasing trends in hemodialysis and living donor kidney transplantation for children and young people in the United Kingdom.

BACKGROUND: The UK Renal Registry is responsible for the national collection and reporting of data on all children receiving long-term kidney replacement therapy [KRT], including kidney transplantation. METHODS: All 13 UK pediatric nephrology centers contributed to providing individual patient data from the pediatric population incident to and prevalent to KRT as per the date 31 December 2018. Data for children aged 16-<18 years were presented separately as some were managed under adult care settings with different methods of data collection. Demographics and biochemical data, including kidney function and prevalence of cardiovascular risk factors [hypertension, hypercholesterolemia, BMI] were reported. RESULTS: Eight hundred and twenty-six children (65.4 per million age-related population [pmarp]) and 199 young people (139.4pmarp) in the United Kingdom were prevalent to KRT on 31 December 2018. Overall, the incidence of KRT during 2018 was 9.1 pmarp and 12.6 pmarp in children and young people, respectively. Congenital anomalies of the kidney and urinary tract (CAKUT) were the most prevalent primary diagnoses (52%). Living and deceased donor transplantation was the most common treatment modality (78%). Patients on dialysis had lower age standardized mean height and weight ranges recorded in comparison to transplant patients [median height z score -1.8 vs. -1.1]. 73.1% patients had one or more cardiovascular disease risk factors. CONCLUSIONS: This study highlights increasing prevalence of hemodialysis and living donor transplantation as modalities for KRT. Of those incident to KRT, the highest patient survival was seen among 8-12 years and lowest <2 years. Moreover, there was a demographic shift from Caucasian toward Asian/other ethnicity and from CAKUT to other primary kidney diseases.

Acute kidney injury identification for pharmacoepidemiologic studies: Use of laboratory electronic acute kidney injury alerts versus electronic health records in Hospital Episode Statistics.

PURPOSE: A laboratory-based acute kidney injury (AKI) electronic-alert (e-alert) system, with e-alerts sent to the UK Renal Registry (UKRR) and collated in a master patient index (MPI), has recently been implemented in England. The aim of this study was to determine the degree of correspondence between the UKRR-MPI and AKI International Classification Disease-10 (ICD-10) N17 coding in Hospital Episode Statistics (HES) and whether hospital N17 coding correlated with 30-day mortality and emergency re-admission after AKI. METHODS: AKI e-alerts in people aged ≥18 years, collated in the UKRR-MPI during 2017, were linked to HES data to identify a hospitalised AKI population. Multivariable logistic regression was used to analyse associations between absence/presence of N17 codes and clinicodemographic features. Correlation of the percentage coded with N17 and 30-day mortality and emergency re-admission after AKI were calculated at hospital level. RESULTS: In 2017, there were 301 540 adult episodes of hospitalised AKI in England. AKI severity was positively associated with coding in HES, with a high degree of inter-hospital variability-AKI stage 1 mean of 48.2% [SD 14.0], versus AKI stage 3 mean of 83.3% [SD 7.3]. N17 coding in HES depended on demographic features, especially age (18-29 years vs. ≥85 years OR 0.22, 95% CI 0.21-0.23), as well as sex and ethnicity. There was no evidence of association between the proportion of episodes coded for AKI with short-term AKI outcomes. CONCLUSION: Coding of AKI in HES is influenced by many factors that result in an underestimation of AKI. Using e-alerts to triangulate the true incidence of AKI could provide a better understanding of the factors that affect hospital coding, potentially leading to improved coding, patient care and pharmacoepidemiologic research.

Associations with kidney transplant survival and eGFR decline in children and young adults in the United Kingdom: a retrospective cohort study.

BACKGROUND: Although young adulthood is associated with transplant loss, many studies do not examine eGFR decline. We aimed to establish clinical risk factors to identify where early intervention might prevent subsequent adverse transplant outcomes. METHODS: Retrospective cohort study using UK Renal Registry and UK Transplant Registry data, including patients aged < 30 years transplanted 1998-2014. Associations with death-censored graft failure were investigated with multivariable Cox proportional hazards. Multivariable linear regression was used to establish associations with eGFR slope gradients calculated over the last 5 years of observation per individual. RESULTS: The cohort (n = 5121, of whom n = 371 received another transplant) was 61% male, 80% White and 36% had structural disease. Live donation occurred in 48%. There were 1371 graft failures and 145 deaths with a functioning graft over a 39,541-year risk period. Median follow-up was 7 years. Fifteen-year graft survival was 60.2% (95% CI 58.1, 62.3). Risk associations observed in both graft loss and eGFR decline analyses included female sex, glomerular diseases, Black ethnicity and young adulthood (15-19-year and 20-24-year age groups, compared to 25-29 years). A higher initial eGFR was associated with less risk of graft loss but faster eGFR decline. For each additional 10 mL/min/1.73m2 initial eGFR, the hazard ratio for graft loss was 0.82 (95% CI 0.79, 0.86), p < 0.0001. However, compared to < 60 mL/min/1.73m2, higher initial eGFR was associated with faster eGFR decline (> 90 mL/min/1.73m2; - 3.55 mL/min/1.73m2/year (95% CI -4.37, - 2.72), p < 0.0001). CONCLUSIONS: In conclusion, young adulthood is a key risk factor for transplant loss and eGFR decline for UK children and young adults. This study has an extended follow-up period and confirms common risk associations for graft loss and eGFR decline, including female sex, Black ethnicity and glomerular diseases. A higher initial eGFR was associated with less risk of graft loss but faster rate of eGFR decline. Identification of children at risk of faster rate of eGFR decline may enable early intervention to prolong graft survival.

Paediatric anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis: an update on renal management.

The anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are a group of disorders characterized by necrotizing inflammation of the small to medium vessels in association with autoantibodies against the cytoplasmic region of the neutrophil. Included in this definition are granulomatosis with polyangiitis (GPA, formerly known as Wegener's granulomatosis), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (formerly known as Churg-Strauss syndrome). AAV are chronic, often relapsing diseases that can be organ or life threatening. Despite immunosuppression, the morbidity and mortality remain high. Renal involvement contributes significantly to the morbidity with high numbers of patients progressing to end-stage kidney disease. Current therapies have enabled improvements in renal function in the short term, but evidence for long-term protection is lacking. In MPA, renal involvement is common at presentation (90%) and often follows a more severe course than that seen in paediatric GPA. Renal biopsy remains the 'gold standard' in diagnosing ANCA-associated glomerulonephritis. While GPA and MPA are considered separate entities, the two are managed identically. Current treatment regimens are extrapolated from adult studies, although it is encouraging to see recruitment of paediatric patients to recent vasculitis trials. Traditionally more severe disease has been managed with the 'gold standard' treatment of glucocorticoids and cyclophosphamide, with remission rates achieved of between 70 and 100%. Other agents employed in remission induction include anti-tumor necrosis factor-alpha therapy and mycophenolate mofetil. Recently, however, increasing consideration is being given to rituximab as a therapy for children in severe or relapsing disease, particularly for those at risk for glucocorticoid or cyclophosphamide toxicity. Removal of circulating ANCA through plasma exchange is a short-term measure reserved for severe or refractory disease. Maintenance therapy usually involves azathioprine. The aim of this article is to provide a comprehensive review of paediatric AAV, with a focus on renal manifestations, and to highlight the recent advances made in therapeutic management.

Continually improving standards of care: The UK Renal Registry as a translational public health tool.

A disease registry uses observational study methods to collect defined data on patients with a particular condition for a predetermined purpose. By providing comprehensive standardised data on patients with kidney disease, renal registries aim to provide a 'real world' representation of practice patterns, treatment and patient outcomes that may not be captured accurately by other methods, including randomised controlled trials. Additionally, using registries to measure variations in outcomes and audit care against standards is crucial to understanding how to improve quality of care for patients in an efficacious and cost-effective manner. Registries also have the potential to be a powerful scientific tool that can monitor and support the translational process between research and routine clinical practice, although their limitations must be borne in mind. In this review, we describe the role of the UK Renal Registry as a tool to support translational research. We describe its involvement across each stage of the translational pathway: from hypothesis generation, study design and data collection, to reporting of long-term outcomes and quality improvement initiatives. Furthermore we explore how this role may bring about improvements in care for adults and children with kidney disease.

Longitudinal changes in body mass index following renal transplantation in UK children.

BACKGROUND: Childhood obesity is a significant health problem in the UK. To date, there is little known about the pattern of change in body mass index (BMI) following renal transplantation in UK paediatric patients. Our objectives in this study were to (i) describe trends in BMI seen in UK patients undergoing renal transplantation in the short and medium term and (ii) identify risk factors predisposing children to excessive weight gain following transplantation. METHODS: A retrospective case note review was performed across 12 of 13 paediatric nephrology centres in the UK, with BMI measurements recorded pre-transplantation and for 4 years thereafter. BMI% was used to assess changes in adiposity over time. International Obesity Taskforce definitions of overweight and obesity were used to identify the prevalence of excess weight pre- and post-renal transplantation. RESULTS: A total of 159 patients (113 boys) under the age of 18 with a functioning kidney transplant were included. Fifty-six patients (35.2%) were under the age of 5 at transplantation. Pre-transplantation, 31.4% of patients were classified as overweight or obese, which increased to 52.8% by the end of follow-up. The majority of patients experienced rapid increases in BMI% over the initial four months post-transplantation, which were sustained for the remainder of the follow-up period. The major risk factor for being overweight or obese at the end of follow-up was having excessive weight pre-transplantation. Four years following transplantation, the prevalence rate of overweight and obesity was much higher in our study cohort than the normal UK childhood population. CONCLUSIONS: The prevalence of patients classified as overweight or obese in the UK paediatric renal cohort is high pre-transplantation and rises subsequently. Those at risk can be identified by an unhealthy BMI pre-transplantation and will require timely intervention with close monitoring in the subsequent post-transplantation period.

Unilateral hypoplastic kidney - a novel highly penetrant feature of familial juvenile hyperuricaemic nephropathy.

BACKGROUND: Familial juvenile hyperuricaemic nephropathy is a rare inherited nephropathy with genetic heterogeneity. Categorised by genetic defect, mutations in uromodulin (UMOD), renin (REN) and hepatocyte nuclear factor-1ß (HNF-1ß) genes as well as linkage to chromosome 2p22.1-21 have previously been identified. Knowledge of the genetics of this phenotype has provided important clues to developmental pathways in the kidney. CASE PRESENTATION: We report a novel phenotype, with the typical features of hyperuricemia and renal deterioration, but with the additional unexpected feature of unilateral renal hypoplasia. Mutation analyses of the existing known genes and genetic loci were negative indicating a new monogenic cause. Interestingly two cousins of the index case did not share the latter feature, suggesting a modifier gene effect. CONCLUSION: Unilateral renal hypo/aplasia is usually sporadic and relatively common, with no genetic cause to date identified. This reported pedigree reveals the possibility that a new, unknown renal developmental gene may be implicated in the FJHN phenotype.

Protocol for a multicentre prospective exploratory mixed-methods study investigating the modifiable psychosocial variables influencing access to and outcomes after kidney transplantation in children and young people in the UK.

INTRODUCTION: Kidney transplantation is the preferred therapy for children with stage 5 chronic kidney disease (CKD-5). However, there is a wide variation in access to kidney transplantation across the UK for children. This study aims to explore the psychosocial factors that influence access to and outcomes after kidney transplantation in children in the UK using a mixed-methods prospective longitudinal design. METHODS: Qualitative data will be collected through semistructured interviews with children affected by CKD-5, their carers and paediatric renal multidisciplinary team. Recruitment for interviews will continue till data saturation. These interviews will inform the choice of existing validated questionnaires, which will be distributed to a larger national cohort of children with pretransplant CKD-5 (n=180) and their carers. Follow-up questionnaires will be sent at protocolised time points regardless of whether they receive a kidney transplant or not. Coexisting health data from hospital, UK renal registry and National Health Service Blood and Transplant registry records will be mapped to each questionnaire time point. An integrative analysis of the mixed qualitative and quantitative data will define psychosocial aspects of care for potential intervention to improve transplant access. ANALYSIS: Qualitative data will be analysed using thematic analysis. Quantitative data will be analysed using appropriate statistical methods to understand how these factors influence access to transplantation, as well as the distribution of psychosocial factors pretransplantation and post-transplantation. ETHICS AND DISSEMINATION: This study protocol has been reviewed by the National Institute for Health Research Academy and approved by the Wales Research Ethics Committee 4 (IRAS number 270493/ref: 20/WA/0285) and the Scotland A Research Ethics Committee (ref: 21/SS/0038). Results from this study will be disseminated across media platforms accessed by affected families, presented at conferences and published in peer-reviewed journals.

Identification of patients undergoing chronic kidney replacement therapy in primary and secondary care data: validation study based on OpenSAFELY and UK Renal Registry.

Objective: To validate primary and secondary care codes in electronic health records to identify people receiving chronic kidney replacement therapy based on gold standard registry data. Design: Validation study using data from OpenSAFELY and the UK Renal Registry, with the approval of NHS England. Setting: Primary and secondary care electronic health records from people registered at 45% of general practices in England on 1 January 2020, linked to data from the UK Renal Registry (UKRR) within the OpenSAFELY-TPP platform, part of the NHS England OpenSAFELY covid-19 service. Participants: 38 745 prevalent patients (recorded as receiving kidney replacement therapy on 1 January 2020 in UKRR data, or primary or secondary care data) and 10 730 incident patients (starting kidney replacement therapy during 2020), from a population of 19 million people alive and registered with a general practice in England on 1 January 2020. Main outcome measures: Sensitivity and positive predictive values of primary and secondary care code lists for identifying prevalent and incident kidney replacement therapy cohorts compared with the gold standard UKRR data on chronic kidney replacement therapy. Agreement across the data sources overall, and by treatment modality (transplantation or dialysis) and personal characteristics. Results: Primary and secondary care code lists were sensitive for identifying the UKRR prevalent cohort (91.2% (95% confidence interval (CI) 90.8% to 91.6%) and 92.0% (91.6% to 92.4%), respectively), but not the incident cohort (52.3% (50.3% to 54.3%) and 67.9% (66.1% to 69.7%)). Positive predictive values were low (77.7% (77.2% to 78.2%) for primary care data and 64.7% (64.1% to 65.3%) for secondary care data), particularly for chronic dialysis (53.7% (52.9% to 54.5%) for primary care data and 49.1% (48.0% to 50.2%) for secondary care data). Sensitivity decreased with age and index of multiple deprivation in primary care data, but the opposite was true in secondary care data. Agreement was lower in children, with 30% (295/980) featuring in all three datasets. Half (1165/2315) of the incident patients receiving dialysis in UKRR data had a kidney replacement therapy code in the primary care data within three months of the start date of the kidney replacement therapy. No codes existed whose exclusion would substantially improve the positive predictive value without a decrease in sensitivity. Conclusions: Codes used in primary and secondary care data failed to identify a small proportion of prevalent patients receiving kidney replacement therapy. Codes also identified many patients who were not recipients of chronic kidney replacement therapy in UKRR data, particularly dialysis codes. Linkage with UKRR kidney replacement therapy data facilitated more accurate identification of incident and prevalent kidney replacement therapy cohorts for research into this vulnerable population. Poor coding has implications for any patient care (including eligibility for vaccination, resourcing, and health policy responses in future pandemics) that relies on accurate reporting of kidney replacement therapy in primary and secondary care data.

Epidemiology of childhood acute kidney injury in England using e-alerts.

Background: Few studies describe the epidemiology of childhood acute kidney injury (AKI) nationally. Laboratories in England are required to issue electronic (e-)alerts for AKI based on serum creatinine changes. This study describes a national cohort of children who received an AKI alert and their clinical course. Methods: A cross-section of AKI episodes from 2017 are described. Hospital record linkage enabled description of AKI-associated hospitalizations including length of stay (LOS) and critical care requirement. Risk associations with critical care (hospitalized cohort) and 30-day mortality (total cohort) were examined using multivariable logistic regression. Results: In 2017, 7788 children (52% male, median age 4.4 years, interquartile range 0.9-11.5 years) experienced 8927 AKI episodes; 8% occurred during birth admissions. Of 5582 children with hospitalized AKI, 25% required critical care. In children experiencing an AKI episode unrelated to their birth admission, Asian ethnicity, young (<1 year) or old (16-<18 years) age (reference 1-<5 years), and high peak AKI stage had higher odds of critical care. LOS was higher with peak AKI stage, irrespective of critical care admission. Overall, 30-day mortality rate was 3% (n = 251); youngest and oldest age groups, hospital-acquired AKI, higher peak stage and critical care requirement had higher odds of death. For children experiencing AKI alerts during their birth admission, no association was seen between higher peak AKI stage and critical care admission. Conclusions: Risk associations for adverse AKI outcomes differed among children according to AKI type and whether hospitalization was related to birth. Understanding the factors driving AKI development and progression may help inform interventions to minimize morbidity.

Disparities in treatment and outcome of kidney replacement therapy in children with comorbidities: an ESPN/ERA Registry study.

Background: Data on comorbidities in children on kidney replacement therapy (KRT) are scarce. Considering their high relevance for prognosis and treatment, this study aims to analyse the prevalence and implications of comorbidities in European children on KRT. Methods: We included data from patients <20 years of age when commencing KRT from 2007 to 2017 from 22 European countries within the European Society of Paediatric Nephrology/European Renal Association Registry. Differences between patients with and without comorbidities in access to kidney transplantation (KT) and patient and graft survival were estimated using Cox regression. Results: Comorbidities were present in 33% of the 4127 children commencing KRT and the prevalence has steadily increased by 5% annually since 2007. Comorbidities were most frequent in high-income countries (43% versus 24% in low-income countries and 33% in middle-income countries). Patients with comorbidities had a lower access to transplantation {adjusted hazard ratio [aHR] 0.67 [95% confidence interval (CI) 0.61-0.74]} and a higher risk of death [aHR 1.79 (95% CI 1.38-2.32)]. The increased mortality was only seen in dialysis patients [aHR 1.60 (95% CI 1.21-2.13)], and not after KT. For both outcomes, the impact of comorbidities was stronger in low-income countries. Graft survival was not affected by the presence of comorbidities [aHR for 5-year graft failure 1.18 (95% CI 0.84-1.65)]. Conclusions: Comorbidities have become more frequent in children on KRT and reduce their access to transplantation and survival, especially when remaining on dialysis. KT should be considered as an option in all paediatric KRT patients and efforts should be made to identify modifiable barriers to KT for children with comorbidities.

Understanding the perspectives of recruiters is key to improving randomised controlled trial enrolment: a qualitative evidence synthesis.

BACKGROUND: Recruiting patients to randomised controlled trials (RCTs) is often reported to be challenging, and the evidence base for effective interventions that could be used by staff (recruiters) undertaking recruitment is lacking. Although the experiences and perspectives of recruiters have been widely reported, an evidence synthesis is required in order to inform the development of future interventions. This paper aims to address this by systematically searching and synthesising the evidence on recruiters' perspectives and experiences of recruiting patients into RCTs.  METHODS: A qualitative evidence synthesis (QES) following Thomas and Harden's approach to thematic synthesis was conducted. The Ovid MEDLINE, CINAHL, EMBASE, PsycInfo, Cochrane Central Register of Controlled Trials, ORRCA and Web of Science electronic databases were searched. Studies were sampled to ensure that the focus of the research was aligned with the phenomena of interest of the QES, their methodological relevance to the QES question, and to include variation across the clinical areas of the studies. The GRADE CERQual framework was used to assess confidence in the review findings. RESULTS: In total, 9316 studies were identified for screening, which resulted in 128 eligible papers. The application of the QES sampling strategy resulted in 30 papers being included in the final analysis. Five overlapping themes were identified which highlighted the complex manner in which recruiters experience RCT recruitment: (1) recruiting to RCTs in a clinical environment, (2) enthusiasm for the RCT, (3) making judgements about whether to approach a patient, (4) communication challenges, (5) interplay between recruiter and professional roles. CONCLUSIONS: This QES identified factors which contribute to the complexities that recruiters can face in day-to-day clinical settings, and the influence recruiters and non-recruiting healthcare professionals have on opportunities afforded to patients for RCT participation. It has reinforced the importance of considering the clinical setting in its entirety when planning future RCTs and indicated the need to better normalise and support research if it is to become part of day-to-day practice. TRIAL REGISTRATION: PROSPERO CRD42020141297 (registered 11/02/2020).