The Infant KIdney Dialysis and Utrafiltration (I-KID) Study: A Stepped-Wedge Cluster-Randomized Study in Infants, Comparing Peritoneal Dialysis, Continuous Venovenous Hemofiltration, and Newcastle Infant Dialysis Ultrafiltration System, a Novel Infant Hemodialysis Device.

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-Conformité Européenne-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.

In vitro measurements of ultrafiltration precision in hemofiltration and hemodialysis devices used in infants.

BACKGROUND: To determine in vitro whether infant hemofiltration and hemodialysis devices can reliably deliver precise ultrafiltration (UF) control. METHODS: We tested the Prismaflex, Aquarius and NIDUS devices which have different circuit types, by in vitro testing with a bag of saline set up as a dummy patient, and monitoring fluid shifts by precise weighing. We looked for differences between the UF rates set and achieved and between the UF result the device displays to the clinician and the true volumes removed, which may lead to clinical errors. We performed short studies at UF settings of zero and 40 ml/h, and with and without simulating poor withdrawal and return lines, and simulated a 4-h treatment session. RESULTS: The Prismaflex setting vs actual errors and display vs actual errors had wide variances, with SDs of 4.1 and 14.0 ml by 15 min, respectively, at both zero and 40 ml/h UF settings. The Aquarius values were wider at 17.3 and 30.3 ml, respectively. For the NIDUS, the mean UF errors were close to zero, and the variances were 0.17 ml. Stop-alarms induced by an obstructed line produced extra UF errors of up to 0.2 ml. A limitation was that we used crystalloid and not colloid for these tests. CONCLUSIONS: Hemotherapy devices with conventional circuits available in the UK do not regulate UF control sufficiently well to recommend for use in small infants, but the NIDUS volumetrically controlled circuit does. All hemotherapy devices intended for small infants should be tested for UF precision. We were unable to test the CARPEDIEM or Aquadex devices. A higher resolution version of the Graphical abstract is available as Supplementary information.

Structural brain abnormalities in adolescents and young adults with congenital heart defect: a systematic review.

AIM: The primary objective of this systematic review is to define and quantify brain structural abnormalities present in adolescents and young adults with complex congenital heart defect (CHD). We also aim to evaluate the extent to which these structural abnormalities are associated with functional outcomes. METHOD: A search of studies examining brain structure by magnetic resonance imaging in adolescents and young adults with complex CHD was performed in Embase, MEDLINE, and Web of Science. A meta-analysis was conducted to determine the odds of brain abnormalities in young people with CHD. Results not included in the meta-analysis were collated using descriptive statistics. RESULTS: Two hundred and fifty-four studies were identified through the literature search. Among these, 14 original studies were included in the review. The odds of brain abnormalities in young people with CHD were 7.9 times higher (p<0.001) than in typically developing comparison individuals. Focal and multifocal lesions were the most common types of abnormality (odds ratio 22.5 [p<0.001]). Preliminary evidence from volumetric, cortical, and microstructural integrity measurements suggests that brain abnormalities are associated with poorer neurocognitive outcomes. INTERPRETATION: This review provides strong evidence that adolescents and young adults with CHD are at increased risk of presenting with structural brain abnormalities and highlights the contribution of advanced quantitative magnetic resonance imaging techniques to identify the subtle but frequent brain alterations in this population. However, more studies are needed to clarify how these abnormalities relate to function. WHAT THIS PAPER ADDS: There is a high prevalence of brain abnormalities in young people with congenital heart defect (CHD). Brain volumes, cortical measurements, and white matter microstructure are altered in young people with CHD. Brain abnormalities are associated with poorer function in young people with CHD.

Urinary tract effects of HPSE2 mutations.

Urofacial syndrome (UFS) is an autosomal recessive congenital disease featuring grimacing and incomplete bladder emptying. Mutations of HPSE2, encoding heparanase 2, a heparanase 1 inhibitor, occur in UFS, but knowledge about the HPSE2 mutation spectrum is limited. Here, seven UFS kindreds with HPSE2 mutations are presented, including one with deleted asparagine 254, suggesting a role for this amino acid, which is conserved in vertebrate orthologs. HPSE2 mutations were absent in 23 non-neurogenic neurogenic bladder probands and, of 439 families with nonsyndromic vesicoureteric reflux, only one carried a putative pathogenic HPSE2 variant. Homozygous Hpse2 mutant mouse bladders contained urine more often than did wild-type organs, phenocopying human UFS. Pelvic ganglia neural cell bodies contained heparanase 1, heparanase 2, and leucine-rich repeats and immunoglobulin-like domains-2 (LRIG2), which is mutated in certain UFS families. In conclusion, heparanase 2 is an autonomic neural protein implicated in bladder emptying, but HPSE2 variants are uncommon in urinary diseases resembling UFS.

Domiciliary administration of intravenous albumin in congenital nephrotic syndrome.

BACKGROUND: Early management of congenital nephrotic syndrome invariably includes the frequent administration of intravenous human albumin solution. The safety and feasibility of intravenous administration of albumin in the patients' home setting has not previously been reported. CASE-DIAGNOSIS/TREATMENT: We report a series of seven paediatric patients whose parents were trained in the administration of albumin via a central venous catheter at home, with the aim of minimising hospital admission or attendances. We describe the clinical course of these patients and complication rates ascribed to this strategy. CONCLUSIONS: Our results demonstrate that home albumin infusion can be performed safely.

Haemodialysing babies weighing <8 kg with the Newcastle infant dialysis and ultrafiltration system (Nidus): comparison with peritoneal and conventional haemodialysis.

BACKGROUND: To compare the efficacy of the Newcastle infant dialysis and ultrafiltration system (Nidus) with peritoneal dialysis (PD) and conventional haemodialysis (HD) in infants weighing <8 kg. METHODS: We compared the urea, creatinine and phosphate clearances, the ultrafiltration precision, and the safety of the Nidus machine with PD in 7 piglets weighing 1-8 kg, in a planned randomised cross-over trial in babies, and in babies for whom no other therapy existed, some of whom later graduated to conventional HD. RESULTS: Two babies entered the randomised trial; 1 recovered rapidly on PD, the other remained on the Nidus as PD failed. Additionally, 9 babies were treated on the Nidus on humanitarian grounds: 3 because of failed PD, and 3 with permanent kidney failure later converted to conventional HD. We haemodialysed 10 babies weighing between 1.8 and 5.9 kg for 2,475 h during 354 Nidus sessions without any clinically important incidents, and without detectable haemolysis. Single-lumen vascular access was used with no blood priming of circuits. The urea, creatinine and phosphate clearances using the Nidus were around 1.5 to 2.0 ml/min in piglets and babies, and were consistently higher than PD clearances, which ranged from about 0.2 to 0.8 ml/min (p ≤ 0.0002 for each chemical). Ultrafiltration was achieved to microlitre precision by the Nidus, but varied widely with PD. Fluid removal using conventional HD was imprecise and resulted in some hypovolaemic episodes requiring correction. CONCLUSION: The Nidus can provide HD in the Pediatric Intensive Care Unit (PICU) and outpatient intermittent HD without blood priming for babies weighing <8 kg, It generates higher dialysis clearances than PD, and delivers more precise ultrafiltration control than either PD or conventional HD.

Maximizing the sensitivity of the indirect radionuclide cystogram: a retrospective audit.

BACKGROUND: The indirect radionuclide cystogram (IRC) has generally been reported as being less sensitive for detecting vesico-ureteric reflux (VUR) than the micturating cystourethrogram (MCUG), so we modified it in an attempt to increase its sensitivity. METHODS: We altered our routine IRC protocol by including the data obtained during failed voids, adding extra imaging sequences at intervals during bladder filling, and by using simple mathematical criteria to determine if VUR was present when visual imaging results were equivocal. We then retrospectively compared the VUR detection rates using the standard and modified techniques. RESULTS: We assessed 707 renal units in 356 children over 3 years. We identified 91 cases of VUR using standard methodology, and 134 (47% more) with the modified technique. Of the extra 43 cases detected, 11 were noted during failed voids, ten were seen within a filling sequence, and 22 were inferred because the renal pelvic activity increased during an interval between two imaging sequences, while the bladder was filling. Mathematical evaluation was helpful in the 39 cases where the increase in activity due to VUR was ≤6 standard deviations greater than the level of background variation in activity. CONCLUSIONS: Additional imaging and mathematical assessment can significantly increase the sensitivity of the IRC for detecting VUR, possibly to equal that of the MCUG.

Multidisciplinary teams, and parents, negotiating common ground in shared-care of children with long-term conditions: a mixed methods study.

BACKGROUND: Limited negotiation around care decisions is believed to undermine collaborative working between parents of children with long-term conditions and professionals, but there is little evidence of how they actually negotiate their respective roles. Using chronic kidney disease as an exemplar this paper reports on a multi-method study of social interaction between multidisciplinary teams and parents as they shared clinical care. METHODS: Phases 1 and 2: a telephone survey mapping multidisciplinary teams' parent-educative activities, and qualitative interviews with 112 professionals (Clinical-psychologists, Dietitians, Doctors, Nurses, Play-specialists, Pharmacists, Therapists and Social-workers) exploring their accounts of parent-teaching in the 12 British children's kidney units. Phase 3: six ethnographic case studies in two units involving observations of professional/parent interactions during shared-care, and individual interviews. We used an analytical framework based on concepts drawn from Communities of Practice and Activity Theory. RESULTS: Professionals spoke of the challenge of explaining to each other how they are aware of parents' understanding of clinical knowledge, and described three patterns of parent-educative activity that were common across MDTs: Engaging parents in shared practice; Knowledge exchange and role negotiation, and Promoting common ground. Over time, professionals had developed a shared repertoire of tools to support their negotiations with parents that helped them accomplish common ground during the practice of shared-care. We observed mutual engagement between professionals and parents where a common understanding of the joint enterprise of clinical caring was negotiated. CONCLUSIONS: For professionals, making implicit knowledge explicit is important as it can provide them with a language through which to articulate more clearly to each other what is the basis of their intuition-based hunches about parents' support needs, and may help them to negotiate with parents and accelerate parents' learning about shared caring. Our methodology and results are potentially transferrable to shared management of other conditions.

Fathers' contributions to the management of their child's long-term medical condition: a narrative review of the literature.

CONTEXT: Fathers' contributions to the management of long-term childhood medical conditions are under-represented in the literature; therefore, the full extent of their involvement is poorly understood by practitioners and researchers, so strategies for promoting their involvement have not yet been fully considered. OBJECTIVE: To review studies of fathers' actual contributions in a wide range of conditions, the potential to optimize their contribution through additional interventions by health professionals and a direction for future research. DESIGN: Narrative review of the literature. METHODS: CINAHL, Medline, PsychInfo and ERIC databases were searched electronically between the years 1995-2008. The terms adherence, adjustment, child, chronic, compliance, concordance, condition, coping, disease, father, illness, information, long-term, management/intervention, mother, role, self-care and treatment were searched for separately and in combination. English language papers reporting primary research were selected and supplemented by hand-searching reference lists. Thirty-five papers (arising from 29 studies) met criteria and were selected for narrative review. RESULTS: Five themes were identified: (i) the impact of long-term conditions on fathers' ability to promote their child's well-being, (ii) factors influencing fathers' involvement in health care, (iii) personal growth/beneficial effects for fathers, (iv) the impact of father's involvement on family functioning and (v) strategies that increase fathers' participation in their child's health care and in research investigating fathers' participation. CONCLUSIONS: The review suggests that fathers' involvement in children's health care can positively impact on fathers', mothers' and children's well-being and family functioning. A range of strategies are identified to inform the promotion of fathers' contributions and future research investigating their input.

Pan-Britain, mixed-methods study of multidisciplinary teams teaching parents to manage children's long-term kidney conditions at home: study protocol.

BACKGROUND: Care of children and young people (children) with long-term kidney conditions is usually managed by multidisciplinary teams. Published guidance recommends that whenever possible children with long-term conditions remain at home, meaning parents may be responsible for performing the majority of clinical care-giving. Multidisciplinary team members, therefore, spend considerable time promoting parents' learning about care-delivery and monitoring care-giving. However, this parent-educative aspect of clinicians' role is rarely articulated in the literature so little evidence exists to inform professionals' parent-teaching interventions. METHODS/DESIGN: This ongoing study addresses this issue using a combination of quantitative and qualitative methods involving the twelve children's kidney units in England, Scotland and Wales. Phase I involves a survey of multidisciplinary team members' parent-teaching interventions using:i) A telephone-administered questionnaire to determine: the numbers of professionals from different disciplines in each team, the information/skills individual professionals relay to parents and the teaching strategies/interventions they use. Data will be managed using SPSS to produce descriptive statisticsii) Digitally-recorded, qualitative group or individual interviews with multidisciplinary team members to explore their accounts of the parent-teaching component of their role. Interviews will be transcribed anonymously and analysed using Framework Technique. Sampling criteria will be derived from analysis to identify one/two unit(s) for subsequent in-depth studyPhase II involves six prospective, ethnographic case-studies of professional-parent interactions during parent-teaching encounters. Parents of six children with a long-term kidney condition will be purposively sampled according to their child's age, diagnosis, ethnicity and the clinical care-giving required; snowball sampling will identify the professionals involved in each case-study. Participants will provide signed consent; data gathering will involve a combination of: minimally-obtrusive observations in the clinical setting and families' homes; de-briefing interviews with participants to obtain views on selected interactions; focussed 'verbatim' field-notes, and case-note reviews. Data gathering will focus on communication between parents and professionals as parents learn care-giving skills and knowledge. Interviews will be digitally recorded and transcribed anonymously. DISCUSSION: This study involves an iterative-inductive approach and will provide a unique, detailed insight into the social context in which professionals teach and parents learn; it will inform professionals' parent-educative roles, educational curricula, and health care policy.

Whole-genome linkage and association scan in primary, nonsyndromic vesicoureteric reflux.

Primary vesicoureteric reflux accounts for approximately 10% of kidney failure requiring dialysis or transplantation, and sibling studies suggest a large genetic component. Here, we report a whole-genome linkage and association scan in primary, nonsyndromic vesicoureteric reflux and reflux nephropathy. We used linkage and family-based association approaches to analyze 320 white families (661 affected individuals, generally from families with two affected siblings) from two populations (United Kingdom and Slovenian). We found modest evidence of linkage but no clear overlap with previous studies. We tested for but did not detect association with six candidate genes (AGTR2, HNF1B, PAX2, RET, ROBO2, and UPK3A). Family-based analysis detected associations with one single-nucleotide polymorphism (SNP) in the UK families, with three SNPs in the Slovenian families, and with three SNPs in the combined families. A case-control analysis detected associations with three additional SNPs. The results of this study, which is the largest to date investigating the genetics of reflux, suggest that major loci may not exist for this common renal tract malformation within European populations.

I-KID study protocol: evaluation of efficacy, outcomes and safety of a new infant haemodialysis and ultrafiltration machine in clinical use: a randomised clinical investigation using a cluster stepped-wedge design.

Introduction: The I-KID study aims to determine the clinical efficacy, outcomes and safety of a novel non-CE-marked infant haemodialysis machine, the Newcastle Infant Dialysis Ultrafiltration System (NIDUS), compared with currently available therapy in the UK. NIDUS is specifically designed for renal replacement therapy in small babies between 0.8 and 8 kg. Methods and analysis: The clinical investigation is taking place in six UK centres. This is a randomised clinical investigation using a cluster stepped-wedge design. The study aims to recruit 95 babies requiring renal replacement therapy in paediatric intensive care units over 20 months. Ethics and dissemination: The study has high parent and public involvement at all stages in its design and parents will be involved in dissemination of results to parents and professionals via publications, conference proceedings and newsletters. The study has has ethics permissions from Tyne and Wear South Research Ethics Committee. Trial registration numbers: IRAS ID number: 170 481MHRA Reference: CI/2017/0066ISRCT Number: 13 787 486CPMS ID number: 36 558NHS REC reference: 16/NE/0008Eudamed number: CIV-GB-18-02-023105Link to full protocol v6.0: https://fundingawards.nihr.ac.uk/award/14/23/26.

Maternal scaffolding and preterm toddlers' visual-spatial processing and emerging working memory.

OBJECTIVE: We examined longitudinal associations among neonatal and socioeconomic risks, maternal scaffolding behaviors, and 24-month visual-spatial processing and working memory in a sample of 73 toddlers born preterm or low birthweight (PT LBW). METHODS: Risk data were collected at hospital discharge and dyadic play interactions were observed at 16-months postterm. Abbreviated IQ scores, verbal/nonverbal working memory, and verbal/nonverbal visual-spatial processing data were collected at 24-months postterm. RESULTS: Higher attention scaffolding and lower emotion scaffolding during 16-month play were associated with 24-month verbal working memory scores. A joint significance test revealed that maternal attention and emotion scaffolding during 16-month play mediated the relationship between socioeconomic risk and 24-month verbal working memory. CONCLUSIONS: These findings suggest areas for future research and intervention with children born PT LBW who also experience high socioeconomic risk.

Childhood chronic-kidney-disease: a longitudinal-qualitative study of families learning to share management early in the trajectory.

OBJECTIVE: To explore the ways families learn to share management during the early stages of childhood chronic-kidney-disease. METHODS: This longitudinal, descriptive study based on the tenets of grounded theory, aimed to derive meaning about family-professional interactions during shared management. Data were obtained from six newly referred families, four renal nurses, four paediatric nephrologists and one dietician through: 36 semi-structured interviews, 21 case-note reviews and four child/parent learning diaries. RESULTS: Three learning stages were identified: dependent (families' understanding was superficial, they lacked underlying knowledge and were totally reliant on professional guidance); co-dependent (families engaged competently in management but still required extensive guidance); independent (families communicated effectively with staff and competently adjusted management within professionally defined parameters). Five families actively shared management from early in the trajectory and progressed to independent learning when, by mutual agreement, professional input to management gradually decreased. The remaining family adopted a passive approach to management, did not progress to independent learning and remained reliant on professional input. CONCLUSIONS: Families in this study demonstrated three learning stages in becoming competent at management. Future research is needed to investigate the ways professionals promote family competence early in the trajectory and the factors that can facilitate or hinder families' progression to independent learning.

Publisher Correction: Genome-wide linkage and association study implicates the 10q26 region as a major genetic contributor to primary nonsyndromic vesicoureteric reflux.

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.

Being visible: PhotoVoice as assessment for children in a school-based psychiatric setting.

BACKGROUND: Recovery-oriented mental health services empower all clients, including youth and their families, to be actively involved in directing their own care. In order to develop person-driven interventions, clinicians must understand what matters from their perspective. Thus, recovery-oriented assessments need self-report measures that adequately capture the domains and content that matter to a range of particular persons. AIM: This study examined if and how PhotoVoice, a participatory research method used to empower and highlight the unique experiences of vulnerable groups, could be used as a recovery-oriented self-report measure for children with a mental health disorder. METHODS: We used PhotoVoice to engage four children with mental health related disorders at a day hospital program for severe behavioural disorders. The children, as co-researchers in this participatory approach, created life books from photographs and images of what mattered to them across nine sessions. To examine the PhotoVoice process, we used ethnographic methods, including child interviews and participant observations in their classes and at recess before, during and after the weekly sessions. Our overarching narrative-phenomenological theoretical framework focused data collection and analysis on what mattered most to the children. RESULTS: The PhotoVoice method engaged and empowered the children in articulating what mattered in their everyday lives from their perspective that resulted in a novel, child-generated domain of 'mattering to others' for future self-report measures, and facilitated changes that generalized outside of the group. We illustrate these results by drawing a particularly illustrative case example from the study. CONCLUSION: The PhotoVoice method foregrounded children's perspectives on what matters more explicitly than clinical or parent perspective on function. SIGNIFICANCE: The participatory philosophy and methods of PhotoVoice provides a viable approach to recovery-oriented self-report measures as well as an occupation-based assessment and intervention.