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.

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.

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.

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.

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

Vesicoureteric reflux (VUR) is the commonest urological anomaly in children. Despite treatment improvements, associated renal lesions - congenital dysplasia, acquired scarring or both - are a common cause of childhood hypertension and renal failure. Primary VUR is familial, with transmission rate and sibling risk both approaching 50%, and appears highly genetically heterogeneous. It is often associated with other developmental anomalies of the urinary tract, emphasising its etiology as a disorder of urogenital tract development. We conducted a genome-wide linkage and association study in three European populations to search for loci predisposing to VUR. Family-based association analysis of 1098 parent-affected-child trios and case/control association analysis of 1147 cases and 3789 controls did not reveal any compelling associations, but parametric linkage analysis of 460 families (1062 affected individuals) under a dominant model identified a single region, on 10q26, that showed strong linkage (HLOD = 4.90; ZLRLOD = 4.39) to VUR. The ~9Mb region contains 69 genes, including some good biological candidates. Resequencing this region in selected individuals did not clearly implicate any gene but FOXI2, FANK1 and GLRX3 remain candidates for further investigation. This, the largest genetic study of VUR to date, highlights the 10q26 region as a major genetic contributor to VUR in European populations.

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.

Change Narratives That Elude Quantification: A Mixed-Methods Analysis of How People with Chronic Pain Perceive Pain Rehabilitation.

Chronic pain negatively impacts health, well-being, and social participation. Effective rehabilitation often hinges on long-term changes in pain-related perceptions and behaviors. However, there are important gaps in understanding how patients perceive these changes. The present pilot study addresses this gap by using qualitative and quantitative methodologies to explore how patients perceive and experience changes in function, participation, and pain-related factors following a chronic pain rehabilitation program. A mixed-method design was used in which the core method was qualitative. Descriptive quantitative data was used to further characterize the sample. Semistructured interviews were conducted 1-6 months following treatment completion. Questionnaires were administered before and after treatment and at follow-up. Interview data was analyzed thematically. Participants' individual descriptive data was compared to established cut-scores and criteria for change. A major theme of personal growth emerged in the qualitative analysis. Participants also discussed the factors that facilitated personal growth and the ongoing challenges to this growth. The quantitative data revealed limited improvement on measures of pain, disability, catastrophizing, and depression. These findings suggest that, despite limited improvement on treatment-related questionnaires, patients can experience an important and enduring sense of personal growth. Clinical and theoretical implications are discussed.

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.

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.

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.

Guidelines to identify abnormalities after childhood urinary tract infections: a prospective audit.

OBJECTIVE: To compare the childhood urinary tract infection (UTI) guidelines from the Royal College of Physicians (RCP) in 1991 and from National Institute of Health and Care Excellence (NICE) (CG54) in 2007 by measuring their efficiency at detecting urinary tract abnormalities. DESIGN: Children with UTIs within the Newcastle Primary Care Trust (population 70,800 children) were referred and imaged according to the RCP guidelines during 2008, and these were compared to the activity that would have been undertaken if we had implemented the CG54 guidelines, including following them through 2011 to identify those with recurrent UTIs. MAIN OUTCOME MEASURES: The numbers of children imaged, the imaging burden and efficiency, and urinary tract abnormalities detected by each guideline. RESULTS: Fewer children would have been imaged by CG54 than RCP (150 vs 427), but its sensitivity was lower, at 44% for detecting scarring, 10% for identifying vesicoureteric reflux and 40% for other abnormalities. Overall, it would have only detected one-quarter of the abnormal cases (8 vs 32) and would have missed five of nine children with scarring, including three with multiple lesions and one with renal impairment. Imposing an age restriction of <8 years to the RCP guidelines would reduce its screening rate by 20% and still detect 90% of the abnormalities. INTERPRETATION: The CG54 guidelines do not alter the imaging efficiency compared to the RCP guidelines, but they are considerably less sensitive.

Does prompt treatment of urinary tract infection in preschool children prevent renal scarring: mixed retrospective and prospective audits.

OBJECTIVE: To test whether active management of urinary tract infections (UTI) in young children by general practitioners can reduce kidney scarring rates. DESIGN: A comparison of two audits in Newcastle, of children aged <8 years, presenting with UTIs ; a retrospective audit of conventional management during 1992-1995 (1990s) versus a prospective audit of direct access management during 2004-2011 (2000s). MAIN OUTCOME MEASURES: Kidney scarring rates, and their relationship with time-to-treat. RESULTS: Children with a first UTI in the 2000s compared to those in the 1990s, were referred younger, were half as likely to have a renal scar (girls OR 0.47, 95% CI 0.29 to 0.76; boys 0.35, 0.16 to 0.81), and were about 12 times more likely to have vesicoureteric reflux without scarring (girls 11.9, 4.3 to 33.5; boys 14.4, 4.3 to 47.6). In the 2000s, general practitioners treated about half the children at first consultation. Children who were treated within 3 days of their symptoms starting were one-third as likely to scar as those whose symptoms lasted longer (0.33, 0.12 to 0.72). INTERPRETATION: Most kidney defects seen in children after UTIs, are acquired scars, and in Newcastle, active management in primary care has halved this rate.

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.

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.

Reliability of the Danish version of the McGill Ingestive Skills Assessment for observation-based measures during meals.

AIM: To establish measurement equivalence in terms of reliability of the Danish version of the Canadian McGill ingestive skills assessment (MISA) for use by occupational therapists. METHODS: A cross-sectional two-rater and test-retest design was applied. A total of 102 elderly medical patients were included consecutively, and were video-recorded during a meal. Raters were paired randomly for each video-case, which was re-scored within three to eight weeks. Reliability was evaluated with the intra-class correlation coefficients (ICC), the standard error of measurement (SEM), the smallest detectable change (SDC), and limits of agreement (LOA). RESULTS: Inter-rater reliability was good to excellent (ICC (1.1) 0.61-0.84) and intra-rater reliability was excellent (ICC (3.1) 0.84-0.93). For the total scale, SEM was 7% between raters and 4% in repeated measurement by the same rater. For the absolute total scale range on 86 points, the SDC was 15.8 between raters and 10.3 in repeated measurement by the same rater. CONCLUSIONS: The reliability of the Danish MISA equals the original version and is suitable for clinical practice. When extending the evaluation of the reproducibility, weaker precision was evident when measurements are repeated by different raters than by the same rater. Therefore further investigation of rater effects is recommended.