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.

Contrasting principal stratum and hypothetical strategy estimands in multi-period crossover trials with incomplete data.

Complete case analyses of complete crossover designs provide an opportunity to make comparisons based on patients who can tolerate all treatments. It is argued that this provides a means of estimating a principal stratum strategy estimand, something which is difficult to do in parallel group trials. While some trial users will consider this a relevant aim, others may be interested in hypothetical strategy estimands, that is, the effect that would be found if all patients completed the trial. Whether these estimands differ importantly is a question of interest to the different users of the trial results. This paper derives the difference between principal stratum strategy and hypothetical strategy estimands, where the former is estimated by a complete-case analysis of the crossover design, and a model for the dropout process is assumed. Complete crossover designs, that is, those where all treatments appear in all sequences, and which compare t treatments over p periods with respect to a continuous outcome are considered. Numerical results are presented for Williams designs with four and six periods. Results from a trial of obstructive sleep apnoea-hypopnoea (TOMADO) are also used for illustration. The results demonstrate that the percentage difference between the estimands is modest, exceeding 5% only when the trial has been severely affected by dropouts or if the within-subject correlation is low.

The Effect of a Product Placement Intervention on Pupil's Food and Drink Purchases in Two Secondary Schools: An Exploratory Study.

Limited research exists on the effectiveness of product placement in secondary schools. We explored the impact of re-positioning sweet-baked goods, fruit, sugar-sweetened beverages (SSBs) and water on pupil's lunchtime purchases in two secondary schools in North-East England. We employed a stepped-wedge design with two clusters and four time periods. The intervention(s) involved re-positioning selected food and drinks to increase and decrease accessibility of 'healthier' and 'less healthy' items, respectively. Unidentifiable smartcard data measured the change in number of pupil's purchasing the above items. McNemar tests were undertaken on paired nominal data in Stata(v15). In School A, pupils purchasing fruit pots from control to intervention increased (n = 0 cf. n = 81; OR 0, 95% CI 0 to 0.04); post-intervention, this was not maintained. In School B, from control to intervention pupil's purchasing sweet-baked goods decreased (n = 183 cf. n = 147; OR 1.2, 95% CI 1 to 1.6). This continued post-intervention (n = 161 cf. n = 122; OR 1.3, 95% CI 1.0 to 1.7) and was similar for SSBs (n = 180 cf. n = 79; OR 2.3, 95% CI 1.7 to 3.0). We found no evidence of other changes. There is some evidence that product placement may positively affect pupil's food and drink purchases. However, there are additional aspects to consider, such as, product availability, engaging canteen staff and the individual school context.

Adjuvant Rituximab-Exploratory Trial in Young People With Graves Disease.

CONTEXT: Remission rates in young people with Graves hyperthyroidism are less than 25% after 2 years of thionamide antithyroid drug (ATD). OBJECTIVE: We explored whether rituximab (RTX), a B-lymphocyte-depleting agent, would increase remission rates when administered with a short course of ATD. METHODS: This was an open-label, multicenter, single-arm, phase 2 trial in young people (ages, 12-20 years) with Graves hyperthyroidism. An A'Hern design was used to distinguish an encouraging remission rate (40%) from an unacceptable rate (20%). Participants presenting with Graves hyperthyroidism received 500 mg RTX and 12 months of ATD titrated according to thyroid function. ATDs were stopped after 12 months and primary outcome assessed at 24 months. Participants had relapsed at 24 months if thyrotropin was suppressed and free 3,5,3'-triiodothyronine was raised; they had received ATD between months 12 and 24; or they had thyroid surgery/radioiodine. RESULTS: A total of 27 participants were recruited and completed the trial with no serious side effects linked to treatment. Daily carbimazole dose at 12 months was less than 5 mg in 21 of 27 participants. Thirteen of 27 participants were in remission at 24 months (48%, 90% one-sided CI, 35%-100%); this exceeded the critical value (9) for the A'Hern design and provided evidence of a promising remission rate. B-lymphocyte count at 28 weeks, expressed as a percentage of baseline, was related to likelihood of remission. CONCLUSION: Adjuvant RTX, administered with a 12-month course of ATD, may increase the likelihood of remission in young people with Graves hyperthyroidism. A randomized trial of adjuvant RTX in young people with Graves hyperthyroidism is warranted.

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.

A comparison of food portion size estimation methods among 11-12 year olds: 3D food models vs an online tool using food portion photos (Intake24).

BACKGROUND: Technology has advanced bringing new cost-effective methods to measure food intake. The aim of the study was to compare food and drink portion estimates from a traditional portion estimation method using 3D food models with portion estimates using an online dietary recall tool, Intake24. METHODS: 11-12 year old children were recruited from secondary schools in Newcastle upon Tyne. Each pupil completed a two-day food diary followed by an interview during which pupils estimated food portion sizes using a range of 3D food models. They also completed Intake24 for the same 2 days. Bland Altman analyses were used to compare mean intake for each method. RESULTS: Seventy pupils completed both portion estimation methods. There was good agreement in food weight estimations between the two methods (geometric mean ratio 1.00), with limits of agreement ranging from minus 35% to plus 53%. Intake24 provided estimates of energy intake that were 1% lower on average than estimates of energy intake using the food models. Mean intakes of all macro and micronutrients using Intake24 were within 6% of the food model estimates. CONCLUSIONS: The findings suggest that there was little difference in portion estimations from the two methods, allowing comparisons to be made between Intake24 data and food diary data collected from same age pupils using 3D food models in previous years.

Reproducibility of 19 F-MR ventilation imaging in healthy volunteers.

PURPOSE: To assess the reproducibility of percentage ventilated lung volume (%VV) measurements in healthy volunteers acquired by fluorine (19 F)-MRI of inhaled perfluoropropane, implemented at two research sites. METHODS: In this prospective, ethically approved study, 40 healthy participants were recruited (May 2018-June 2019) to one of two research sites. Participants underwent a single MRI scan session on a 3T scanner, involving periodic inhalation of a 79% perfluoropropane/21% oxygen gas mixture. Each gas inhalation session lasted about 30 seconds, consisting of three deep breaths of gas followed by a breath-hold. Four 19 F-MR ventilation images were acquired per participant, each separated by approximately 6 minutes. The value of %VV was determined by registering separately acquired 1 H images to ventilation images before semi-automated image segmentation, performed independently by two observers. Reproducibility of %VV measurements was assessed by components of variance, intraclass correlation coefficients, coefficients of variation (CoV), and the Dice similarity coefficient. RESULTS: The MRI scans were well tolerated throughout, with no adverse events. There was a high degree of consistency in %VV measurements for each participant (CoVobserver1 = 0.43%; CoVobserver2 = 0.63%), with overall precision of %VV measurements determined to be within ± 1.7% (95% confidence interval). Interobserver agreement in %VV measurements revealed a high mean Dice similarity coefficient (SD) of 0.97 (0.02), with only minor discrepancies between observers. CONCLUSION: We demonstrate good reproducibility of %VV measurements in a group of healthy participants using 19 F-MRI of inhaled perfluoropropane. Our methods have been successfully implemented across two different study sites, supporting the feasibility of performing larger multicenter clinical studies.

Randomised trial of block and replace vs dose titration thionamide in young people with thyrotoxicosis.

OBJECTIVE: First-line treatment of thyrotoxicosis in young people is thionamide anti-thyroid drug (ATD) in a blocking dose with levothyroxine replacement (block and replace, BR) or in a smaller dose tailored to render the patient euthyroid (dose titration, DT). Our objective was to determine which regimen provides more stable biochemical control. DESIGN: A multi-centre phase III, open-label randomised trial comparing BR with DT in patients aged 2-17 years with newly diagnosed thyrotoxicosis at 15 UK centres. METHODS: Patients were randomised shortly after diagnosis and treated for 3 years. The primary outcome was the percentage of serum thyroid-stimulating hormone (TSH) levels in the reference range between 6 months and 3 years. Secondary outcomes included the proportion of Free thyroxine (FT4) levels in the reference range, adverse event frequency and 4 years outcome (remission/relapse). RESULTS: Eighty-two patients were randomised, with details on clinical course in 81 (62 Female); 40 were allocated to BR (41 DT). Three withdrew with one ineligible. The mean percentage of serum TSH within reference range was 60.2% in BR and 63.8% in DT patients; adjusted difference 4.3%, 95% CI (-7.8 to 16.4); P = 0.48. Proportions for FT4 were 79.2% in BR and 85.7% in DT patients; adjusted difference 6.8%, (-0.2 to 15.6); P = 0.13. Three patients developed neutropenia - all on BR. 6 BR and 10 DT patients were in remission at 4y. CONCLUSION: This randomised trial has shown no evidence to suggest that BR, when managing the young patient with thyrotoxicosis, is associated with improved biochemical stability when compared to DT.

Highly efficient stepped wedge designs for clusters of unequal size.

The stepped wedge design (SWD) is a form of cluster randomized trial, usually comparing two treatments, which is divided into time periods and sequences, with clusters allocated to sequences. Typically all sequences start with the standard treatment and end with the new treatment, with the change happening at different times in the different sequences. The clusters will usually differ in size but this is overlooked in much of the existing literature. This paper considers the case when clusters have different sizes and determines how efficient designs can be found. The approach uses an approximation to the variance of the treatment effect, which is expressed in terms of the proportions of clusters and of individuals allocated to each sequence of the design. The roles of these sets of proportions in determining an efficient design are discussed and illustrated using two SWDs, one in the treatment of sexually transmitted diseases and one in renal replacement therapy. Cluster-balanced designs, which allocate equal numbers of clusters to each sequence, are shown to have excellent statistical and practical properties; suggestions are made about the practical application of the results for these designs. The paper concentrates on the cross-sectional case, where subjects are measured once, but it is briefly indicated how the methods can be extended to the closed-cohort design.

Associations of vitamin D status with dietary intakes and physical activity levels among adults from seven European countries: the Food4Me study.

PURPOSE: To report the vitamin D status in adults from seven European countries and to identify behavioural correlates. METHODS: In total, 1075 eligible adult men and women from Ireland, Netherlands, Spain, Greece, UK, Poland and Germany, were included in the study. RESULTS: Vitamin D deficiency and insufficiency, defined as 25-hydroxy vitamin D3 (25-OHD3) concentration of <30 and 30-49.9 nmol/L, respectively, were observed in 3.3 and 30.6% of the participants. The highest prevalence of vitamin D deficiency was found in the UK and the lowest in the Netherlands (8.2 vs. 1.1%, P < 0.05). In addition, the prevalence of vitamin D insufficiency was higher in females compared with males (36.6 vs. 22.6%, P < 0.001), in winter compared with summer months (39.3 vs. 25.0%, P < 0.05) and in younger compared with older participants (36.0 vs. 24.4%, P < 0.05). Positive dose-response associations were also observed between 25-OHD3 concentrations and dietary vitamin D intake from foods and supplements, as well as with physical activity (PA) levels. Vitamin D intakes of ≥5 µg/day from foods and ≥5 µg/day from supplements, as well as engagement in ≥30 min/day of moderate- and vigorous-intensity PA were associated with higher odds (P < 0.05) for maintaining sufficient (≥50 nmol/L) 25-OHD3 concentrations. CONCLUSIONS: The prevalence of vitamin D deficiency varied considerably among European adults. Dietary intakes of ≥10 µg/day of vitamin D from foods and/or supplements and at least 30 min/day of moderate- and vigorous-intensity PA were the minimum thresholds associated with vitamin D sufficiency.

Development of food photographs for use with children aged 18 months to 16 years: Comparison against weighed food diaries - The Young Person's Food Atlas (UK).

Traditional dietary assessment methods, used in the UK, such as weighed food diaries impose a large participant burden, often resulting in difficulty recruiting representative samples and underreporting of energy intakes. One approach to reducing the burden placed on the participant is to use portion size assessment tools to obtain an estimate of the amount of food consumed, removing the need to weigh all foods. An age range specific food atlas was developed for use in assessing children's dietary intakes. The foods selected and portion sizes depicted were derived from intakes recorded during the UK National Diet and Nutrition Surveys of children aged 1.5 to 16 years. Estimates of food portion sizes using the food atlas were compared against 4-day weighed intakes along with in-school / nursery observations, by the research team. Interviews were conducted with parents the day after completion of the diary, and for children aged 4 to 16 years, also with the child. Mean estimates of portion size consumed were within 7% of the weight of food recorded in the weighed food diary. The limits of agreement were wide indicating high variability of estimates at the individual level but the precision increased with increasing age. For children 11 years and over, agreement with weighed food diaries, was as good as that of their parents in terms of total weight of food consumed and of intake of energy and key nutrients. The age appropriate food photographs offer an alternative to weighed intakes for dietary assessment with children.

Comparison of INTAKE24 (an Online 24-h Dietary Recall Tool) with Interviewer-Led 24-h Recall in 11-24 Year-Old.

Online dietary assessment tools offer a convenient, low cost alternative to traditional dietary assessment methods such as weighed records and face-to-face interviewer-led 24-h recalls. INTAKE24 is an online multiple pass 24-h recall tool developed for use with 11-24 year-old. The aim of the study was to undertake a comparison of INTAKE24 (the test method) with interviewer-led multiple pass 24-h recalls (the comparison method) in 180 people aged 11-24 years. Each participant completed both an INTAKE24 24-h recall and an interviewer-led 24-h recall on the same day on four occasions over a one-month period. The daily energy and nutrient intakes reported in INTAKE24 were compared to those reported in the interviewer-led recall. Mean intakes reported using INTAKE24 were similar to the intakes reported in the interviewer-led recall for energy and macronutrients. INTAKE24 was found to underestimate energy intake by 1% on average compared to the interviewer-led recall with the limits of agreement ranging from minus 49% to plus 93%. Mean intakes of all macronutrients and micronutrients (except non-milk extrinsic sugars) were within 4% of the interviewer-led recall. Dietary assessment that utilises technology may offer a viable alternative and be more engaging than paper based methods, particularly for children and young adults.

Penalised logistic regression and dynamic prediction for discrete-time recurrent event data.

We consider methods for the analysis of discrete-time recurrent event data, when interest is mainly in prediction. The Aalen additive model provides an extremely simple and effective method for the determination of covariate effects for this type of data, especially in the presence of time-varying effects and time varying covariates, including dynamic summaries of prior event history. The method is weakened for predictive purposes by the presence of negative estimates. The obvious alternative of a standard logistic regression analysis at each time point can have problems of stability when event frequency is low and maximum likelihood estimation is used. The Firth penalised likelihood approach is stable but in removing bias in regression coefficients it introduces bias into predicted event probabilities. We propose an alterative modified penalised likelihood, intermediate between Firth and no penalty, as a pragmatic compromise between stability and bias. Illustration on two data sets is provided.

Does the use of passive or active consent affect consent or completion rates, or dietary data quality? Repeat cross-sectional survey among school children aged 11-12†years.

OBJECTIVES: An expectation of research is that participants should give fully informed consent. However, there is also a need to maximise recruitment to ensure representativeness. We explored the impact of passive or active parental consent on consent, completion rates and on dietary data quality in a survey among children aged 11-12 years. SETTING: Six middle schools in North-East England. PARTICIPANTS: All children aged 11-12 years attending the six middle schools were eligible to participate (n=1141). PRIMARY OUTCOMES: whether or not each eligible child's parent gave consent and provided a complete dietary diary; whether or not a child completed their dietary diary but only among children who agreed to participate, and whether or not children providing diaries were classified as an under-reporter or not. RESULTS: Parents were more likely to consent passively than actively. This difference was greater among the more deprived: OR 16.9 (95% CI 5.7 to 50.2) in the least and 129.6 (95% CI 39.9 to 420.6) in the most deprived quintile (test for interaction: method of consent by level of deprivation, p=0.02). For all children eligible, completion was more likely if passive consent was used (OR 2.8, 95% CI 2.2 to 3.7). When only children who gave consent are considered, completion was less likely when passive rather than active consent was used (OR 0.6, 95% CI 0.4 to 0.9). Completion rate decreased as level of deprivation increased; we found no evidence that the OR for the method of consent varied by level of deprivation. There was no evidence that the quality of dietary data, as measured by an assessment of under-reporting, differed by method of consent (OR 0.8, 95% CI 0.5 to 1.2). CONCLUSIONS: Passive consent led to a higher participation rate and a more representative sample without compromising data quality.

Design and baseline characteristics of the Food4Me study: a web-based randomised controlled trial of personalised nutrition in seven European countries.

Improving lifestyle behaviours has considerable potential for reducing the global burden of non-communicable diseases, promoting better health across the life-course and increasing well-being. However, realising this potential will require the development, testing and implementation of much more effective behaviour change interventions than are used conventionally. Therefore, the aim of this study was to conduct a multi-centre, web-based, proof-of-principle study of personalised nutrition (PN) to determine whether providing more personalised dietary advice leads to greater improvements in eating patterns and health outcomes compared to conventional population-based advice. A total of 5,562 volunteers were screened across seven European countries; the first 1,607 participants who fulfilled the inclusion criteria were recruited into the trial. Participants were randomly assigned to one of the following intervention groups for a 6-month period: Level 0-control group-receiving conventional, non-PN advice; Level 1-receiving PN advice based on dietary intake data alone; Level 2-receiving PN advice based on dietary intake and phenotypic data; and Level 3-receiving PN advice based on dietary intake, phenotypic and genotypic data. A total of 1,607 participants had a mean age of 39.8 years (ranging from 18 to 79 years). Of these participants, 60.9 % were women and 96.7 % were from white-European background. The mean BMI for all randomised participants was 25.5 kg m(-2), and 44.8 % of the participants had a BMI ≥ 25.0 kg m(-2). Food4Me is the first large multi-centre RCT of web-based PN. The main outcomes from the Food4Me study will be submitted for publication during 2015.

Did school food and nutrient-based standards in England impact on 11-12Y olds nutrient intake at lunchtime and in total diet? Repeat cross-sectional study.

INTRODUCTION: In September 2009, middle and secondary schools in England were required to comply with food and nutrient-based standards for school food. We examined the impact of this policy change on children's lunchtime and total dietary intake. METHODS: We undertook repeat cross-sectional surveys in six Northumberland middle schools in 1999-2000 and 2009-10. Dietary data were collected from 11-12 y olds (n = 298 in 1999-2000; n = 215 in 2009-10). Children completed two consecutive 3-day food diaries, each followed by an interview. Linear mixed effect models examined the effect of year, lunch type and level of socio-economic deprivation on children's mean total dietary intake. RESULTS: We found both before and after the introduction of the food and nutrient-based standards children consuming a school lunch, had a lower per cent energy from saturated fat (-0.5%; p = 0.02), and a lower intake of sodium (-143 mg; p = 0.02), and calcium (-81 mg; p = 0.001) in their total diet, compared with children consuming a home-packed lunch. We found no evidence that lunch type was associated with mean energy, or absolute amounts of NSP, vitamin C and iron intake. There was marginal evidence of an association between lunch type and per cent energy NMES (p = 0.06). In 1999-2000, children consuming a school lunch had a higher per cent energy from fat in their total diet compared with children consuming a home-packed lunch (2.8%), whereas by 2009-10, they had slightly less (-0.2%) (year by lunch type interaction p<0.001; change in mean differences -3%). CONCLUSIONS: We found limited evidence of an impact of the school food and nutrient-based standards on total diet among 11-12 year olds. Such policies may need to be supported by additional measures, including guidance on individual food choice, and the development of wider supportive environments in school and beyond the school gates.

A repeat cross-sectional study examining the equitable impact of nutritional standards for school lunches in England in 2008 on the diets of 4-7y olds across the socio-economic spectrum.

BACKGROUND: The 2008 nutritional standards for primary school lunch in England improved nutritional content. The impact on socio-economic inequalities is unknown. We examine the impact of the nutritional standards on children's nutrient intake at lunchtime and in total diet by level of deprivation. METHODS: We conducted cross-sectional studies in 12 English primary schools before and after legislation. Dietary intake was recorded for 4-7y olds using a validated, prospective four-day food diary. Socio-economic status was estimated using the Index of Multiple Deprivation; three groups of approximately equal sizes were created. Linear, mixed-effect models explored the effect of year, lunch type (school or home-packed lunch), level of deprivation and the interaction(s) between these factors on children's diets. RESULTS: 368 and 624 children participated in 2003-4 and 2008-9 respectively. At lunchtime, between 2003-4 and 2008-9, the increase in non-starch polysaccharide (NSP) intake was larger in the least compared to the most deprived group (difference in mean change 0.8 mg; 95% CI 0.4, 1.3). There were similar differences in mean changes for iron (0.3 mg; 0.2, 0.4) and zinc (0.3 mg; 0.1, 0.5). In total diet, differential effects were observed for NSP, iron and zinc; we found no evidence these changes were associated with lunch type. Lunch type was associated with changes in per cent energy from non-milk-extrinsic sugars (NMES) and vitamin C. Per cent energy from NMES was lower and vitamin C intake higher in school lunches in 2008-9 compared with 2003-4. The corresponding differences in home-packed lunches were not as marked and there were subtle but statistically significant effects of the level of deprivation. CONCLUSIONS: By 2008-9, NMES at lunchtime and in total diet was lower for children consuming a school lunch; this change was equitable across the deprivation groups. Vitamin C intake increased more for children in the most deprived group, narrowing the socio-economic inequality. A range of significant differential effects of the nutritional standards were observed and important socio-economic inequalities in dietary intake remain. Additional interventions to promote equitable nutrition in children are needed to support legislative measures and maximise their impact.

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.

Dropout in crossover and longitudinal studies: is complete case so bad?

We discuss inference for longitudinal clinical trials subject to possibly informative dropout. A selection of available methods is reviewed for the simple case of trials with two timepoints. Using data from two such clinical trials, each with two treatments, we demonstrate that different analysis methods can at times lead to quite different conclusions from the same data. We investigate properties of complete-case estimators for the type of trials considered, with emphasis on interpretation and meaning of parameters. We contrast longitudinal and crossover designs and argue that for crossover studies there are often good reasons to prefer a complete case analysis. More generally, we suggest that there is merit in an approach in which no untestable assumptions are made. Such an approach would combine a dropout analysis, an analysis of complete-case data only, and a careful statement of justified conclusions.