BackgroundA clinical paedodontic randomised controlled trial (FiCTION) provided the opportunity to explore recruitment and retention challenges in The National Health Service (NHS) primary dental care settings.PurposeTo investigate parental attitudes towards their child's participation in a dental randomised controlled trial (RCT).MethodsParents whose child(ren) (aged 3-7 years) were participants in a dental RCT or who had been screened for the trial but did not participate were asked to consent to be contacted regarding completing a questionnaire and a semi-structured face-to-face qualitative interview. Using a purposive, maximum variation sampling strategy a subsample of parents who had completed the questionnaire study completed an interview. Data were coded using NVivo and the Framework Method of thematic analysis applied.ResultsThe 18 parents consenting to an interview indicated positive attitudes towards research in primary dental care. There were no noticeable contrasting views of good dental health, or perceptions of facilitators and barriers thereof, between parents whose child(ren) were FiCTION participants and those whose child(ren) were not. Research involvement did not appear to be a major incentive to attend a particular practice, and while parents viewed research-active dental practices favourably, they did not always understand why their practice was research-active (especially for those not participating in FiCTION). Most FiCTION parents felt comfortable with the concept of trial withdrawal or requesting a change in treatment arm. However, parents did not always have complete knowledge or understanding of the research study in which they had been invited to participate. While FiCTION parents had overall greater understanding of research, concepts such as randomisation were hard for most parents to grasp.ConclusionsParents valued dental research in primary care but perceived it as complex and challenging. Further research should explore the best methods to achieve engagement with patients in primary dental care research.

Most research funders and journals now require researchers to make their data available for sharing. There is a growing body of literature on research participants' attitudes towards health data sharing, but less evidence regarding views of participants taking part in longitudinal studies, clinical trials or public health research.1,664 respondents from the UK (participants in longitudinal studies ALSPAC and ACONF and members of Patient and Public Involvement (PPI) groups completed a questionnaire survey exploring attitudes towards data sharing, including consent and data storage. Respondents were most concerned about privacy and data security and highlighted concerns about open access and sharing with commercial organisations.

Objectives:To pilot and assess the feasibility of a fully remote effectiveness evaluation of a novel smartphone self-management app for people living with Sjögren disease (SjD), including evaluating trial procedures and app engagement. Methods:We conducted a double-blind, randomised, fully-remote pilot feasibility of a self-management smartphone app (Sjogo) containing interactive components with an information-only control app. After completing onboarding procedures, participants were allocated to a trial arm following download from Apple App and Google Play stores. Participants completed symptoms and quality of life measures at baseline and (at two further timepoints (5-7 and 10-13 weeks) after download. Engagement with the app was measured with number and duration of logins. Results:996 participants downloaded Sjogo to their smartphone. 871 (87.45%) consented to take part in the study and 617 (61.95%) completed the onboarding procedures and baseline measures and were randomised to the full-version of the app (n = 318) or control-version (n = 299). In-app randomisation produced balanced groups. In week 1 engagement was higher in the intervention group m = 4.76 logins (S.D. 8.06) than the control group m = 3.47 (S.D. 2.75). At week 2 engagement dropped in both groups (intervention group m = 1.17, SD 4.56, control m = 0.40, SD 0.93). Outcome completion rates at subsequent timepoints were 36.63% (weeks 5-7) and 27.39% (weeks 10-13). Conclusion:It is feasible to collect data fully remotely, automate trial procedures, and recruit participants to a randomised controlled trial of a self-management smartphone app for people with SjD through app stores. However, app engagement and outcome completion rates could be improved.

The World Health Organisation’s (WHO) 2021 report on the global tobacco epidemic highlighted dangers of e-cigarettes to youth and stated that countries without e-cigarette regulations leave themselves particularly vulnerable to the activities of tobacco and related industries. Nigeria, with a large proportion of young people, is now considering regulating e-cigarettes. This qualitative study aimed to provide insight into the factors that could influence such regulation. Three participants were recruited using purposive sampling and interviewed as representatives of potential Nigerian e-cigarette regulators. Interview transcripts were analysed using thematic analysis. Five factors that could influence e-cigarette regulations in Nigeria were identified i.e., existing regulatory framework; research evidence; public health considerations; economic considerations; and e-cigarette industry. The young population of Nigeria and WHO recommendations on regulation of e-cigarettes provides stimulus for Nigerian authorities to impose some form of regulation of e-cigarettes in Nigeria. Adhering to the Nigerian regulatory framework requires compliance with existing policies, and multiple stakeholder consultation. The involvement of multiple stakeholders can be beneficial for inclusivity but may introduce three competing interests, public health, economic, and industry interest, which may conflict and unduly influence e-cigarette regulations in Nigeria. Regulators should prioritise regulatory measures that serve the most essential needs of the population. The findings of this research is beneficial to decision makers as it can help with regulatory preparedness by promoting factors with positive potential to help Nigeria meet its regulatory responsibilities while minimizing factors that do the opposite.

BACKGROUND:Self-care is a priority outcome for children and young people with neurodisabilities, their parents and therapists, but there is little evidence about paediatric therapy interventions for children's self-care in the United Kingdom. METHODS:Children with neurodisabilities, parents, therapists and teachers participated in this mixed methods study. Data were collected by interviews and observations of routine therapy appointments. Inductive analysis was used to define aspects of self-care and describe how therapists deliver care to support self-care. The Behaviour Change Technique Taxonomy v1 was used to deductively code the data to identify self-care intervention ingredients and related mechanisms of change. RESULTS:Sixteen aspects of self-care were described; five were commonly targeted in therapy practice: being safe, dressing, eating and drinking, keeping clean and toileting. Three clusters of intervention techniques describe current practice. Cluster 1 comprises instruction on how to perform the behaviour, behavioural rehearsal and practice, graded tasks and demonstration of the behaviour. These techniques target knowledge, skills and beliefs about capabilities as mechanisms of change to improve self-care. Cluster 2 comprises restructuring the social environment, social support and adding objects to the environment. These techniques target the social and physical environment as mechanisms of change. Cluster 3 comprises reducing negative emotions, information about emotional consequences, monitoring of emotional consequences and exposure. Although not commonly used, these techniques target children's and young people's emotions. Children and young people's autonomy as a central concept in self-care is supported in relation to selecting therapy goals and outcomes of therapy. CONCLUSIONS:A clear description of current therapy practice is provided for comparison against new or alternative interventions for self-care. The most common technique involves instructing how to perform specific behaviours, with methods like behavioural rehearsal and graded tasks aiding in acquiring knowledge, skills and beliefs about capabilities. Additionally, interventions focus on modifying the environment through social influences and resources and addressing children's and young people's emotions.

Smoking is a key contributor to health inequalities, particularly impacting oral health. Periodontal (gum) health is significantly affected by smoking. With their extensive reach, regular and frequent patient contact, and potential teachable moments, dental teams are well placed to support patients to stop smoking. This is currently mainly provided through Very Brief Advice (VBA) interventions and so there is scope to enhance the cessation support offered. A large definitive trial is needed to confirm whether this would lead to improved smoking quit rates, improved oral health, and be good value for money. The ENHANCE-D trial is a multi-centre, pragmatic, definitive, 3-arm, parallel group, individually randomised controlled superiority trial, including an internal pilot, conducted in NHS dental settings. In total, 1215 patients who are current regular smokers will be randomly allocated using a 1:2:2 ratio to the following: (i) VBA; (ii) the offer of a standard course of Nicotine Replacement Therapy (NRT); (iii) or the offer of an e-cigarette starter kit. A subgroup of patients with periodontitis (gum disease) will have additional oral examinations and samples collected. The primary outcome is biochemically verified smoking abstinence at 6 months. A key secondary outcome is the percentage of periodontal sites with probing pocket depths (PPDs) ≥ 5 mm at 6 months in the periodontitis subgroup. Participants will be blinded to the purpose of the trial and not be aware of the treatment packages. Periodontal health outcomes will be recorded by trained and aligned assessors, blinded to intervention arm. Participant recruitment started in July 2022 with an internal pilot progressing to the main trial in May 2023. A qualitative process evaluation will explore participants’ experiences of receiving the study interventions, alongside the views of dental teams, NHS commissioners, service managers, and policymakers. An economic evaluation will include a cost-effectiveness analysis and a cost–benefit analysis. This will be the largest contemporary randomised trial of smoking cessation interventions in dental settings and one of the first to evaluate enhanced interventions. E-cigarettes were included as an intervention due to growing evidence of their effectiveness. They will be compared to VBA and NRT, and oral health outcomes assessed. The multi-centre, pragmatic design of this trial supports the external validity and potential for impacting clinical practice. ISRCTN 13158982. Registered on 10 May 2022. https://www.isrctn.com/ISRCTNISRCTN13158982

BACKGROUND:Current UK measures of early spoken language comprehension require manipulation of toys and/or verbal responses and are not accessible to children with severe motor impairments. The Computer-Based Instrument for Low motor Language Testing (C-BiLLT) (originally validated in Dutch) is a computerized test of spoken language comprehension that children with motor disorders control using their usual response methods. AIMS:To create a UK version of the C-BiLLT, evaluate its validity and reliability, and assess its practicability for children with motor disorders. METHODS & PROCEDURES:The C-BiLLT was translated into British English and items were adapted to ensure familiarity to UK children. A total of 424 children (233 females, 191 males) aged 1:6-7:5 (years:months) without developmental disabilities were recruited from North East England. Children completed the UK C-BiLLT and Preschool Language Scales 5 (PLS-5) for convergent validity evaluation and either the visual reception subtest of the Mullen Scales of Early Learning (MSEL) (children aged 1:8-5:5) or Ravens Coloured Progressive Matrices (CPM) (ages 5:6-7:5) to assess divergent validity. A total of 33 children completed the UK C-BiLLT within 4 weeks of initial assessment for test-retest reliability assessment (intraclass correlation coefficient-ICC). Internal consistency was assessed using Cronbach's alpha and exploratory factor analysis examined structural validity. A total of 24 children (10 female, 14 male; aged 4-12 years) with non-progressive motor disorders who use augmentative and alternative communication (AAC), rated the UK C-BiLLT's ease of use and completed British Picture Vocabulary Scales (BPVS) and CPM as for convergent and divergent validity testing. OUTCOMES & RESULTS:Internal consistency was high for children without motor disorders (α = 0.96). Exploratory factor analysis extracted two factors, together explaining 68% of the total variance. Test-retest reliability was excellent (ICC = 0.95; 0.90-0.98 95% confidence interval-CI). UK C-BiLLT scores correlated highly with PLS-5 (r = 0.91) and MSEL (r = 0.81), and moderately with CPM (r = 0.41); and increased across full-year age-bands (F(6, 407) = 341.76, p = < 0.001, η2 = 0.83). A total of 19 children with motor disorders rated the UK C-BiLLT as easy/ok to use; two judged it hard; three declined to rate the ease of use. Their UK C-BiLLT scores correlated highly with BPVS (r = 0.77) and moderately with CPM (r = 0.57). CONCLUSIONS & IMPLICATIONS:The UK C-BiLLT is a valid, reliable measure of early spoken language development and is potentially practicable for children with motor disorders. It may facilitate international research on the language development of children with motor disorders and evaluation of intervention at the national level. WHAT THIS PAPER ADDS:What is already known on the subject Young children with motor disorders have difficulties accessing standardized assessments of language comprehension that require children to handle objects or to speak a response. What this paper adds to the existing knowledge This study demonstrates the validity and reliability of a UK translation of the C-BiLLT and suggests that the measure is feasible for children with motor disorders who use AAC and have a reliable method of response via computer access. What are the potential or clinical implications of this work? The UK C-BiLLT is a useful addition to the limited tools currently available to assess early spoken language comprehension of children with motor disorders.

Abstract Background Critically unwell babies in intensive care units may develop acute renal failure. Options for renal replacement therapy are limited by their small size and available technology. Objectives To determine the clinical efficacy, outcomes and safety profile of the NIDUS® (a novel infant haemodialysis device) for babies under 8 kg, compared with current renal replacement therapy. Design A clinical investigation using a non-blinded cluster stepped wedge design with paediatric intensive care units randomised to sequences. Setting Paediatric intensive care units in six UK hospitals. Participants Children under 8 kg who required renal replacement therapy for fluid overload or biochemical disturbance. Interventions Continuous renal replacement therapy was provided by the usual methods: peritoneal dialysis and continuous haemofiltration (during control periods) and by the NIDUS (during intervention periods), a novel device designed for babies with a smaller circuit and filter and volumetric control of ultrafiltration. Main outcome measures Primary outcome was precision of ultrafiltration compared with prescription; secondary outcomes included biochemical clearances, accuracy of reported ultrafiltration and mortality. Data sources Bedside study data collected by weighing bags of fluid entering and leaving the device were entered into the study database along with case descriptors. Some secondary outcome data was collected via the Paediatric Intensive Care Audit Network. Results Ninety-seven participants were recruited by study closure, 62 to control and 35 to intervention. The primary outcome was obtained from 62 control but only 21 intervention patients, largely because of technical difficulties using NIDUS. The analysis comparing the available primary outcomes showed that ultrafiltration with NIDUS was closer to that prescribed than with control: standard deviations controls 18.75, intervention 2.95 (ml/hour), adjusted ratio 0.13, 95% confidence interval (0.03 to 0.71); p = 0.018. The mean clearances for creatinine, urea and phosphate were lower on peritoneal dialysis than NIDUS, which were in turn lower than continuous veno-venous haemofiltration. The variability in the clearances was in the same order. Of the 62 control patients, 10 died (2/62 on peritoneal dialysis; 7/13 on continuous haemofiltration) before discharge from paediatric intensive care unit (16%), compared with 12 out of 35 (34%) in the NIDUS group: p = 0.04, 95% confidence interval for difference (0 to 36%). Harms No important adverse events occurred and the NIDUS has an acceptable safety profile compared with other renal replacement therapies in this critically ill population with multi-organ failure. Mortality was lowest for Peritoneal Dialysis, highest for continuous haemofiltration, with the NIDUS in-between. Only one serious adverse device event which was reported to the Medicines and Healthcare products Regulatory Agency. Conclusions NIDUS works effectively, delivering appropriate blood clearances and accurate, controllable fluid removal (ultrafiltration), indicating that it has an important place alongside other dialysis modalities for infant renal replacement therapy. Future work Findings from this study indicate some modifications are required to NIDUS to improve usability. Further studies on use of the NIDUS device in other populations of babies for example those with chronic renal failure, and long-term outcomes are required. Trial registration This trial is registered as ISRCTN 13787486. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation Programme (NIHR award ref: 14/23/26) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 1. See the NIHR Funding and Awards website for further award information. Plain language summary Why do this study? Some children in intensive care are so poorly that their kidneys do not work well, and they need help, called dialysis, to get rid of fluid and chemicals from their blood. For babies, we currently use peritoneal dialysis, where fluid is cycled in and out of the tummy, or adapted machines designed for bigger children (continuous veno-venous haemofiltration). A new machine, the NIDUS® (Allmed, www.allmedgroup.com), was developed specifically for babies weighing under 8 kg with much smaller tubing. NIDUS worked well when studied in Newcastle but needed testing elsewhere. What was the question? How well does NIDUS work compared to other dialysis methods? What are the problems? What did we do? The study was done in six paediatric intensive care units who used their usual dialysis methods (=control) in the first part of the study and then later swapped to using the NIDUS (=intervention). What did we find? We recruited 97 participants, 62 to control (49 peritoneal dialysis, 13 continuous veno-venous haemofiltration) and 35 intervention (NIDUS). We found NIDUS provided much better control of fluid removal. The CVVH machines were more efficient at blood cleaning than NIDUS, which was better than peritoneal dialysis. What does this mean? We learnt a lot about babies needing kidney support in paediatric intensive care units and that all methods have advantages and disadvantages. We showed that NIDUS could be very useful for some participants because it cleans blood effectively and gives accurate, controllable fluid removal. We have gathered important information to help us improve NIDUS to make it easier to use and run. Many parents responded to our questionnaire and most told us they felt it was acceptable to be approached about taking part in research despite the circumstances. This is very important for future research studies. We are very grateful to families for their generosity in becoming involved in this study. Scientific summary Background Critically unwell babies in paediatric intensive care units (PICUs) may develop acute renal failure and require management with renal replacement therapy. Although mortality and morbidity vary and are related to the underlying diagnosis, survival of babies in paediatric intensive care is worse for those with fluid overload. Babies requiring renal replacement treatment present specific therapeutic challenges because of their small size and the current technology available. Difficulties with vascular access and blood flows, fluid balance, loss of circuits, filter clotting and hypotensive episodes at initiation are all described in the literature. The need for new solutions and improved technology is well recognised. Continuous veno-venous haemofiltration (CVVH) machines in use in the UK at the time of this study are not approved for use in babies weighing <8 kg (<20 kg in the USA), but because of lack of alternatives, they are frequently used by clinicians outside of licence and recommendations. Objectives The objectives of the I-KID study were to determine the clinical efficacy, outcomes and safety profile of a novel non-CE marked infant haemodialysis (HD) device for babies under 8 kg: the NIDUS® (Allmed, www.allmedgroup.com) compared to current renal replacement treatment. Methods The study used a cluster-randomised standard stepped wedge (SW) design with 4 periods and 3 sequences, hence 12 treatment cells. The clusters were PICUs. Conventional therapy [peritoneal dialysis (PD) or CVVH] was used in the control cells, with the NIDUS used in the intervention cells. Each site was trained in setting up and using the NIDUS before switching to an intervention period. The design meant that all participating centres had the chance to use both treatments during the course of the study. PICU nurses were competency-assessed before each site could begin using the intervention; 24-hour on-call nurse/clinician telephone support was provided from Newcastle. Using a SW design permitted phased training on the NIDUS and allowed within-centre comparisons to contribute to the treatment estimate. The setting was PICUs in six hospitals in the UK, chosen because of their experience of performing renal replacement treatment in babies, and willingness to collaborate. Informed consent was sought from parents/guardians of children weighing from 800 g to 8 kg who required renal replacement treatment for fluid overload or biochemical disturbance (babies with suspected inborn errors of metabolism, for example leading to hyperammonaemia were excluded). Because of the urgency of requirement to start renal replacement treatment in some cases, where necessary, deferred consent was sought as soon as possible. Interventions During control periods, renal replacement treatment was provided by the usual methods in each PICU: PD and CVVH and, after a period of training and competency assessment, by the NIDUS during intervention periods. In addition, one infant being treated on an extracorporeal membrane oxygenation circuit during the control period had renal replacement treatment added by the integration of a HD filter inserted into that circuit. There was no blinding. Outcome measures Primary outcome The first observation of precision of fluid removal [ultrafiltration (UF)] from an episode lasting at least one hour for CVVH or the NIDUS, or at least 5 hours for PD within 48 hours of the start of renal replacement treatment. Secondary outcomes (related to the primary outcome) average of all precision values observed on the patient biochemical clearance rates for creatinine, urea and phosphate precision of observed versus reported fluid removal (CVVH and NIDUS only). Other secondary outcomes survival haemodynamic status (drop in blood pressure after connection to CVVH or dialysis device, requiring intervention of fluid bolus or administration of inotropes) number of ventilator-free days during renal replacement treatment completion of intended renal replacement treatment course need for additional vascular or dialysis access unplanned change in circuits exposure to blood transfusion bleeding events anticoagulant use. Secondary outcomes from questionnaires parent/guardian experience staff acceptability and usability of device. Data sources Data were collected on UF by timed weighing of fluid delivery and output bags used by the CVVH (Prismaflex® and Aquarius®) and NIDUS. For PD using manual circuits, volumes delivered and removed were measured by the bedside nurse. Timed UF and blood samples were performed to calculate biochemical clearances. Bedside study data were entered into a bespoke study database along with case descriptors. Some secondary outcome data were collected via the Paediatric Intensive Care Audit Network (PICANet), as this was already established in use at study sites. Results The planned sample size was 95 participants. By study closure 97 participants were recruited, 62 to control and 35 to intervention. Descriptive summaries were similar in both control and intervention groups; around half the participants had unplanned admissions to paediatric intensive care and approximately a third were transferred from outside hospitals. Renal replacement treatment was required post surgery in 52% of control and 40% of intervention cases. For those requiring renal replacement treatment post surgery this involved cardiac bypass surgery in 97% of controls and 84% of intervention participants. Systolic blood pressure, median [interquartile range (IQR)] control 68 (59, 78), intervention 68 (60, 86) mmHg and need for mechanical ventilation (>80%) were similar. The median (IQR) age in controls 10.5 (7, 38) days was similar to that in the intervention group 11 (7, 61) days; the range of age of participants was between 1 and 477 days (approximately 15 months). The median (IQR) weights 3.2 (2.9, 3.9) and 3.7 (3.1, 5.6) kg were similar between control and intervention. Availability of primary outcome The primary outcome was available on all 62 control patients but only 21 of the 35 intervention patients. This was due to a range of reasons including difficulties in obtaining the information needed to compute the UF rate (accurate timing and weighing data) and technical difficulties using the NIDUS: full details are in the report. Precision of UF Analysis comparing the 62 control patients with the 21 intervention patients with a primary outcome showed that UF with the NIDUS was closer to that prescribed than with control: standard deviations (SDs) controls 18.75, intervention 2.95 (ml/hour), adjusted ratio 0.13, 95% confidence interval (0.03 to 0.71); p = 0.018. For the NIDUS and CVVH devices, an important measure was to compare the difference between the actual fluid removal measured and that reported by the device. This had a mean closer to zero for the NIDUS than CVVH (means −0.44 vs. 11.6 ml/hour, respectively), with less variation in NIDUS than CVVH (SDs 3.2 vs. 28.4 ml/hour). Biochemical clearances The initial intention was to compare clearance rate on NIDUS with the control group. However, for these variables combining PD and CVVH in this way proved to be misleading because NIDUS clearances rates were intermediate between those of PD and CVVH. The clearance for creatinine on PD was smaller and less variable (mean 0.08, SD 0.03 ml/min/kg) than on the NIDUS (mean 0.46, SD 0.30 ml/min/kg), which was in turn smaller and less variable than for CVVH (mean 1.20, SD 0.72 ml/min/kg). The pattern was repeated for urea: PD (0.12, 0.06), NIDUS (0.48, 0.30) and CVVH (1.15, 0.67), all in ml/min/kg, and also for phosphate: PD (0.07, 0.04), NIDUS (0.44, 0.27) and CVVH (1.16, 0.71), all in ml/min/kg. All pairwise treatment comparisons of means and of SDs gave p < 0.001. More detail on the UF and clearances are provided in the results section of the main report. Survival Of the 62 participants receiving control treatment, 54 survived to 30 days (87%) and 52 (84%) survived until discharge. For the 35 participants in the NIDUS group, 25 survived to 30 days (71%) and 23 (66%) survived to discharge. For the participants receiving PD 47 of 48 participants (98%) survived to 30 days, and 46 (96%) survived to discharge, whereas for the 13 participants on CVVH the corresponding values were 7 (54%) and 6 (46%). The participant receiving ECMO plus haemodialysis is not included in these figures. Exposure to blood transfusion while on renal replacement treatment Median (IQR) haemoglobin concentrations prior to starting renal replacement treatment were similar. However, only 7 (15%) of the participants on PD required a blood transfusion, whereas 12 (92%) of the 13 on CVVH required blood transfusion and 27 (77%) of those on NIDUS required blood transfusion. Five of the ten babies, whose CVVH circuits were via conventional central venous access lines, required priming with blood rather than saline, but none of the NIDUS circuits needed this. Use of inotropes or fluid bolus Hundred per cent of participants on PD, seventy-seven per cent of those on CVVH and eighty-nine per cent of those on NIDUS were reported as receiving additional fluid bolus (defined as 80 ml/kg by the PICANet) or inotropes infusion in the first 48 hours of renal replacement treatment. Safety reporting There were 27 adverse events (AEs) across 23 participants (15 control, 8 intervention). Adverse device events were only reported for the NIDUS intervention. There was one adverse device event which was possibly related to the NIDUS device/tubing set. There were 17 serious adverse events across 15 participants (8 control, 7 intervention). One serious adverse device event was reported throughout the study. Conclusions The I-KID study provides important new information about renal replacement treatment in babies on PICUs. The results show that the UF obtained with the NIDUS was closer to that prescribed than with control. Moreover, the UF reported by the NIDUS was a reliable reflection of the true UF. Clinically both aspects are important. While measurement of UF with PD is easy and accurate, the uncontrollability and unpredictability of UF is clinically recognised as an issue. It is also very important to be able to rely on the information given by a dialysis/filtration device being accurate for the clinician to make appropriate adjustments to the patient’s overall fluid balance. Conversely, if the device gives inaccurate information to the clinical team it contributes to uncertainty and difficulty in overall fluid management. Manufacturers are aware of the inherent imprecision of their devices and give warnings in their technical documentation and indeed, concern regarding variability in fluid removal was the initial reason for licensing restriction of CVVH devices. There is currently only one device licensed for babies under 8 kg, the Cardio-Renal Pediatric Dialysis Emergency Machine (CARPEDIEM®) (Medtronic, www.medtronic.com), which was not in use in the UK during this study time and was not available for study in I-KID. The clearance comparison between PD and NIDUS reflects that found in a previous study, whereas this is the first comparison between CVVH (Prismaflex® and Aquarius®) and NIDUS. Given the greater blood flow and larger filter surface area of the CVVH devices, these results are as anticipated. Clinically, the NIDUS would provide adequate biochemical clearance for controlling biochemical disturbance in babies with acute renal failure. Many babies requiring renal replacement treatment in PICUs are critically unwell, as reflected by the vast majority of participants in I-KID having multi-organ failure; most were on positive pressure ventilatory support. There was a very high use of inotrope infusions, but it is unclear whether this was largely ‘routine use’ in babies postoperatively after cardiac surgery or related to hypotensive episodes. The survival data reflects the high mortality associated with the underlying clinical diagnoses. Mortality was lowest for PD and highest for CVVH, with NIDUS in between. Babies who are unwell and particularly post surgical may require blood transfusion for a number of different reasons. Few babies on PD required blood transfusion but rates were much higher in babies treated with CVVH and NIDUS. Those participants may have been more unwell or the process of haemofiltration and dialysis renal replacement treatment increases the need for blood transfusion. Half of the CVVH circuits connected to the babies’ central venous lines required blood priming, but none of the NIDUS circuits did. Recruitment was high in the first part of the study, when most participants were entering the control phase, but was less good as the study progressed and sites were mainly enrolling babies into the intervention phase. The study faced a number of challenges to delivery, including moratoria on non-COVID-19 research during the early phases of the COVID pandemic. The number of control cases on PD (vs. CVVH) was higher than we had estimated. There were AEs reported in both control subgroups and in intervention cases. NIDUS was shown to have an acceptable safety profile compared with other modalities used in this critically unwell population. Implications for health care The I-KID study had high input from public and parents at all stages from the early development phase onwards and this was crucial to ensuring acceptability to participant parents. Importantly, most parents who responded to the questionnaire indicated they felt it was acceptable to be approached about taking part in research despite the circumstances. This is important for future research studies in critical care. The study required and achieved a high degree of support from clinicians and nursing staff. An important safety profile has been created and user feedback from I-KID has provided vital information on improvements required to NIDUS to improve usability. Peritoneal dialysis is likely to remain a commonly used technique for babies with less severe renal failure who require less intensive dialysis. Many postoperative babies (especially those undergoing cardiac surgery) have a PD catheter inserted during surgery, which is sometimes just used for draining ascitic fluid and can be easily used for dialysis if required. However, insertion of a PD catheter is not without its risks, and there is room for future studies questioning the best immediate postoperative renal support modality. Where PD is not possible or fails, it is clear that NIDUS provides a good therapeutic option to be considered. Largely the results were in concordance with clinical experience of renal replacement treatment in babies and with previous NIDUS animal and compassionate use reports. The results show that the intervention device, NIDUS, works effectively delivering appropriate blood clearances and accurate, controllable fluid removal (UF), with an appropriate safety profile, indicating that it has an important place alongside other dialysis modalities in the management of babies with renal failure. Trial registration This trial is registered as ISRCTN 13787486. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation Programme (NIHR award ref: 14/23/26) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 1. See the NIHR Funding and Awards website for further award information.

Context: Chronic kidney disease (CKD) leads to alterations in fibroblast growth factor 23 (FGF23) and the renal-bone axis. This may be partly driven by altered inflammation and iron status. Vitamin D supplementation may reduce inflammation. Objective and methods: Older adults with early CKD (estimated glomerular filtration rate (eGFR) 30-60 ml/min/1.73 m(2); CKDG3a/b; n = 35) or normal renal function (eGFR >90 ml/min/1.73 m(2); CKDG1; n = 35) received 12,000, 24,000 or 48,000 IU D-3/month for 1 year. Markers of the renal-bone axis, inflammation and iron status were investigated pre- and post-supplementation. Predictors of c-terminal and intact FGF23 (cFGF23; iFGF23) were identified by univariate and multivariate regression. Results: Pre-supplementation, comparing CKDG3a/b to CKDG1, plasma cFGF23, iFGF23, PTH, sclerostin and TNF alpha were significantly higher and Klotho, 1,25-dihydroxyvitamin D and iron were lower. Post-supplementation, only cFGF23, 25(OH)D and IL6 differed between groups. The response to supplementation differed between eGFR groups. Only in the CKDG1 group, phosphate decreased, cFGF23, iFGF23 and procollagen type I N-propeptide increased. In the CKDG3a/b group, TNF alpha significantly decreased, and iron increased. Plasma 25(OH)D and IL10 increased, and carboxy-terminal collagen crosslinks decreased in both groups. In univariate models cFGF23 and iFGF23 were predicted by eGFR and regulators of calcium and phosphate metabolism at both time points; IL6 predicted cFGF23 (post-supplementation) and iFGF23 (pre-supplementation) in univariate models. Hepcidin predicted post-supplementation cFGF23 in multivariate models with eGFR. Conclusion: Alterations in regulators of the renal-bone axis, inflammation and iron status were found in early CKD. The response to vitamin D-3 supplementation differed between eGFR groups. Plasma IL6 predicted both cFGF23 and iFGF23 and hepcidin predicted cFGF23.

Introduction Smoking is a major contributor to health inequalities in the UK. The ENHANCE-D trial is evaluating three smoking cessation interventions (nicotine replacement therapy [NRT], electronic cigarettes [ECs] or ‘very brief advice') delivered in NHS primary dental care. This qualitative study aimed to provide insight into the factors that could influence the adoption of the interventions in these settings. Methods Interviews were conducted at two timepoints. Purposive maximum variation sampling was used to recruit and interview a total of 24 dental patients, 12 dental professionals and three NHS dental commissioners. Thematic analysis was carried out using normalisation process theory as an analytical framework. Results Dental settings were perceived as an appropriate location to deliver smoking cessation interventions. Patients had several motivating and demotivating factors regarding use of NRTs or ECs; they often had negative preconceptions. Financial considerations were major influencers for both patients and dental teams. The time pressures for dental practices were identified as a major barrier. Some practical issues, such as procurement and stock supply, would need to be considered if the ENHANCE-D interventions were to be implemented in routine practice. Conclusion Primary dental care teams are well-placed to deliver smoking cessation interventions. However, a number of facilitators and deterrents have been identified and strategic changes are needed for successful implementation.

Background Pregnancy weight management interventions can improve maternal diet, physical activity, gestational weight gain, and postnatal weight retention. UK guidelines were published in 2010 but health professionals report multiple complex barriers to practice. GLOWING used social cognitive theory to address evidence-based barriers to midwives’ implementation of weight management guidelines into routine practice. This paper reports the pilot trial outcomes relating to feasibility and acceptability of intervention delivery and trial procedures. Methods GLOWING was a multi-centre parallel-group pilot cluster RCT comparing the delivery of a behaviour change intervention for midwives (delivered as training workshops) with usual practice. The clusters were four NHS Trusts in Northeast England, randomised to intervention or control arms. Blinding of allocation was not possible due to the nature of the intervention. We aimed to deliver the intervention to all eligible midwives in the intervention arm, in groups of 6 midwives per workshop, and to pilot questionnaire data collection for a future definitive trial. Intervention arm midwives’ acceptability of GLOWING content and delivery was assessed using a mixed methods questionnaire, and pregnant women’s acceptability of trial procedures by interviews. Quantitative data were analysed descriptively and qualitative data thematically. Results In intervention arm Trusts, 100% of eligible midwives ( n = 67) were recruited to, and received, the intervention; however, not all workshops had the planned number of attendees (range 3–8). The consent rate amongst midwives randomised ( n = 100) to complete questionnaires was 74% ( n = 74) (95% CI 65%, 83%), and overall completion rate 89% ( n = 66) (95% CI 82%, 96%). Follow-up response rate was 66% ( n = 49) (95% CI 55%, 77%), with a marked difference between intervention (39%, n = 15) and control (94%, n = 34) groups potentially due to the volume of research activities. Overall, 64% ( n = 47) (95% CI 53%, 75%) completed both baseline and follow-up questionnaires. Midwives viewed the intervention as acceptable and directly relevant to routine practice. The least popular components related to scripted role-plays. Pregnant women viewed the recruitment and trial processes to be acceptable. Conclusions This rigorously conducted pilot study demonstrated feasibility intervention delivery and a high level of acceptability amongst participants. It has provided information required to refine the intervention and trial protocol, enhancing confidence that a definitive trial could be carried out. Trial registration ISRCTN46869894; retrospectively registered 25th May 2016, www.isrctn.com/ISRCTN46869894 .

Objectives:Renal replacement therapy (RRT) options are limited for small babies because of lack of available technology. We investigated the precision of ultrafiltration, biochemical clearances, clinical efficacy, outcomes, and safety profile for a novel non-Conformite Europeenne-marked hemodialysis device for babies under 8 kg, the Newcastle Infant Dialysis Ultrafiltration System (NIDUS), compared with the current options of peritoneal dialysis (PD) or continuous venovenous hemofiltration (CVVH). Design:Nonblinded cluster-randomized cross-sectional stepped-wedge design with four periods, three sequences, and two clusters per sequence. Setting:Clusters were six U.K. PICUs. Patients:Babies less than 8 kg requiring RRT for fluid overload or biochemical disturbance. Interventions:In controls, RRT was delivered by PD or CVVH, and in interventions, NIDUS was used. The primary outcome was precision of ultrafiltration compared with prescription; secondary outcomes included biochemical clearances. Measurements and Main Results:At closure, 97 participants were recruited from the six PICUs (62 control and 35 intervention). The primary outcome, obtained from 62 control and 21 intervention patients, showed that ultrafiltration with NIDUS was closer to that prescribed than with control: sd controls, 18.75, intervention, 2.95 (mL/hr); adjusted ratio, 0.13; 95% CI, 0.03-0.71; p = 0.018. Creatinine clearance was smallest and least variable for PD (mean, sd) = (0.08, 0.03) mL/min/kg, larger for NIDUS (0.46, 0.30), and largest for CVVH (1.20, 0.72). Adverse events were reported in all groups. In this critically ill population with multiple organ failure, mortality was lowest for PD and highest for CVVH, with NIDUS in between. Conclusions:NIDUS delivers accurate, controllable fluid removal and adequate clearances, indicating that it has important potential alongside other modalities for infant RRT.

IntroductionSurvival following out of hospital cardiac arrest (OHCA) is less than 10% in England. Although early defibrillation with an automated external defibrillator (AED) can more than double survival rates, they are used in just 2.4% of witnessed OHCAs in the UK. Increased usage has the potential to save lives. This study investigated the awareness amongst university campus users of the location and purpose of AEDs and explored their reported willingness and confidence to use one in OHCA.MethodsA cross-sectional intercept interview study was conducted using a questionnaire administered to members of the public, staff and students at eight locations across the Newcastle University campus during May to July 2022 using convenience sampling. Informed consent from participants and University ethical approval were obtained, and demographic data were collected. An image was used to establish whether participants could identify an AED (Figure 1), and binary responses on willingness to obtain and use an AED were reported as proportions and compared with Chi-square. Self-reported confidence of use was reported on a scale of 1-10, and summarised using median (IQR) comparing those who had and had not received first aid training; comparisons were made using Mann-Whitney. Barriers to using an AED were reported as free-text responses, and analysed thematically.Results170 interviews were completed (31 university staff [18.2%], 54 students [31.8%] and 85 members of the public [50.0%]). 58 (34.1%) had never received first aid training. Overall, 149 (87.6%) were able to identify an AED, and 142 (83.5%) correctly described their function (Table 1). 150 participants (88.2%) reported they would be willing to retrieve an AED in an emergency, and 136 (80.0%) were willing to use one. However, just 65 (31.2%) reported that they knew how to use an AED. The median confidence rating for using an AED, across all respondents, was 6/10 (interquartile range 4/10 to 7/10) and tended to be higher amongst those that had received first aid training than those that had not (medians: 7/10 vs 3.5/10, P=0.003). The most common barriers to using AEDs were lack of knowledge and training, and fear of causing harm (Figure 2).ConclusionParticipants were generally aware of the purpose of an AED and tended to be willing to retrieve and use one. However, they reported limited knowledge of how to access and use an AED, and lack of confidence in doing so. The reported barriers suggest that these issues are likely to be amenable to educational strategies, which is reinforced by our finding that first aid training was associated with increased reported confidence to retrieve and use an AED. OHCA is a time-critical emergency; and increases in population willingness and confidence to use an AED has the potential to save lives.Conflict of InterestNone

National Institute for Health Research Postdoctoral Fellowship (reference PDF-2011-04-034).

Preconception obesity is associated with adverse pregnancy outcomes and deprivation. The postnatal period provides an opportunity for preconception intervention. There is a lack of published postnatal behaviour and weight data to inform intervention needs. Secondary analysis of the GLOWING study explored postnatal diet, physical activity (PA) and weight among women living with obesity in deprivation. Thirty-nine women completed food frequency and PA questionnaires and provided weight measurement(s) between 3–12 months postnatal. Women’s diet and PA fell short of national guidelines, especially for fruit/vegetables (median 1.6–2.0 portions/day) and oily fish (0–4 g/day). PA was predominantly light intensity. Patterns in weight change across time points indicated postnatal weight loss compared with 1st (median −0.8 to −2.3 kg) and 3rd-trimester weights (−9.0 to −11.6 kg). Weight loss was higher among women without excessive gestational weight gain (GWG) (−2.7 to −9.7 kg) than those with excessive GWG (2.3 to −1.8 kg), resulting in postnatal weight measurements lower than their 1st trimester. These pilot data suggest preconception interventions should commence in pregnancy with a focus on GWG, and postnatal women need early support to achieve guideline-recommendations for diet and PA. Further research in a larger population could inform preconception intervention strategies to tackle inequalities in maternal obesity and subsequent pregnancy outcomes.

Bone and renal metabolism are regulated by common factors and there is extensive cross-talk between these organs (the 'renal-bone-axis'). Ageing is associated with physiological changes including reduced bone mass, renal function and tissue sensitivity to regulatory hormones, impacting the renal-bone axis. We aimed to investigate the influence of estimated Glomerular Filtration Rate (eGFR) on plasma concentrations of vitamin D metabolites, Wnt signalling and bone metabolism in a dose ranging vitamin D3 RCT (12,000 IU, 24,000 IU, 48,000 IU/month for 1 year; n = 379, >70 y) with a baseline eGFR > 30 mL/min/1.73 m2. Participants were categorised on basis of eGFR (≥60 or mL/min/1.73 m2) based on 5 commonly used algorithms for eGFR. Differences between eGFR categories were tested with ANCOVA. Before supplementation commenced, a lower eGFR was associated with significantly higher concentrations of c-terminal and intact Fibroblast Growth Factor-23 (cFGF23; iFGF23), intact Parathyroid Hormone (iPTH) and Sclerostin (SOST) and lower Klotho, 1,25-dihydroxy Vitamin D (1,25(OH)2D) and Dickkopf-related Protein 1 (DKK1) concentrations. Differences between eGFR groups in 25-hydroxy Vitamin D (25(OH)D), 24,25-dihydroxy Vitamin D (24,25(OH)2D) and iPTH were only detected with eGFR based on Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Modification in Diet for Renal Disease (MDRD-4) algorithms. Differences in Bone Mineral Density and Content (BMD; BMC) and bone turnover markers were detected only with Cockcroft-Gault (CG). Pre- and post- supplementation comparisons showed differences in the response to supplementation by eGFR group. Plasma 25(OH)D, 24,25(OH)2D, 1,25(OH)2D and DKK1 increased and iPTH and C-terminal telopeptide (CTX) decreased in both groups. Plasma iFGF23, bone specific alkaline phosphatase (BAP) and Procollagen 1 intact N-terminal Propeptide (PINP) increased and phosphate decreased only in the group with eGFR ≥ 60 mL/min/1.73 m2. Findings were largely consistent across all eGFR algorithms. Post-supplementation, cFGF23, iFGF23, iPTH and SOST remained significantly higher in the lower eGFR group. Plasma 1,25(OH)2D and Klotho did no longer differ between eGFR groups. This was found for all eGFR algorithms, with the exception of iPTH and iFGF23, which were not significantly different with eGFR based on CG. Differences in BMD and BMC were detected with CKD-EPI-creatinine and MDRD-4 but not GC. This study showed that even a moderate decline in eGFR is associated with alterations in vitamin D metabolism, Wnt signalling and bone turnover markers. Renal function influenced the response to vitamin D supplementation. Supplementation increased Vitamin D metabolites in the group with moderate renal impairment to concentrations comparable to those found in the group with normal renal function. However, although CTX decreased, an increase in bone formation markers was not found in the group with eGFR 60 mL/min/1.73 m2. In conclusion, vitamin D supplementation had beneficial effects on markers of the renal-bone axis in older people with both normal and impaired renal function.

© The Author(s) 2022. Medical Council on Alcohol and Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. Alcohol and Alcoholism, 2022, 57(2) 261–269 https://doi.org/10.1093/alcalc/agab087 Advance Access Publication Date: 3 February 2022 Article

As part of the internal pilot of the EMPOWER trial investigating the second-line antiemetic therapies in severe emesis in pregnancy ( https://www.isrctn.com/ISRCTN16924692 ), a qualitative study of women’s views was carried out, to improve our understanding of why women did, or did not, consent to participation in the trial. Interviews were also conducted with site research staff, to broaden our analysis and explore other factors affecting recruitment. The sample comprised women who accepted or declined trial participation (n=21) and site research staff (n=22). A structured topic guide was used, in four email interviews and 17 telephone interviews with women, and semi-structured telephone interviews were carried out with staff. Of the women interviewed, seven had declined trial participation, and of the staff interviewed, 16 were research midwives/research nurses and six were principal investigators. All transcripts were checked for accuracy, anonymised and entered into NVIVO12 for indexing and retrieval. Data was analysed using a reflexive thematic analytic approach. In total, 72 codes were generated from the thematic analysis, and 36 from each sample group. Three key themes based on all the interviews were (a) the diversity of recruitment pathways and boundaries of care, (b) the impact of trial complexity on recruitment and staff morale and (c) the ethics of caring for a patient with emesis. Ethical issues discussed included the use of double dummy and time to treat, particularly those suffering severely from the effects of nausea and vomiting. To illustrate these themes, staff perspectives are given more prominence. The main reason the trial was stopped related to the high proportion of women ineligible for recruitment due to prior treatment with study drug(s) because of unanticipated changes in clinical practice. The qualitative results also demonstrate the impact of the trial on women and staff and highlight how the diversity of referral pathways, boundaries of care and the complexity of the trial and protocol resulted in additional barriers to successful trial recruitment. Qualitative work in pilot and feasibility studies of a clinical trial is recommended, to evaluate whether recruitment strategies remain viable in unanticipated contexts. Trial registration number ISRCTN16924692 . Date: 08/01/2018