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.
Mātauranga Māori (Māori knowledge) is grounded in place-based, multi-generational knowledge and the connection of that knowledge with the environments from which it is derived. It takes for granted ...that all elements of the natural world are related, and it is upon those relationships that survival depends. A Māori worldview advocates for the responsibility of each generation to pass onto their descendants at least as good a supply of resources as they, themselves, had inherited. For Māori, the wellness of the environment is a direct reflection on the wellness of the people. This article provides an overview of a practical mātauranga Māori-led marine restoration project in Ōhiwa harbour. The transdisciplinary project worked with a traditional Māori master weaver and kaumātua (tribal elders) to develop biodegradable taura kuku (green-lipped mussel spat settlement lines, hereafter taura kuku) made from traditional Māori plant biowaste and other natural materials. The taura kuku proved a successful tool for the recruitment and settlement of wild mussel spat assisting shellfish restoration and increasing marine biodiversity in the culturally and ecologically important mahinga kai (traditional food basket) of Ōhiwa harbour.
Full text
Available for:
BFBNIB, GIS, IJS, KISLJ, NUK, PNG, UL, UM, UPUK
Salmonella enterica serovar Typhi (S. typhi) causes typhoid fever. We show that exposure of S. typhi to neuroendocrine stress hormones results in haemolysis, which is associated with the release of ...haemolysin E in membrane vesicles. This effect is attributed to increased expression of the small RNA micA and RNA chaperone Hfq, with concomitant downregulation of outer membrane protein A. Deletion of micA or the two‐component signal‐transduction system, CpxAR, abolishes the phenotype. The hormone response is inhibited by the β‐blocker propranolol. We provide mechanistic insights into the basis of neuroendocrine hormone‐mediated haemolysis by S. typhi, increasing our understanding of inter‐kingdom signalling.
Exposure of the human pathogen Salmonella Typhi to host neuroendocrine stress hormones causes the release of hemolysin E in membrane vesicles. Hemolysis depends on the two component system CpxAR and involves the small RNA micA, the RNA chaperone Hfq, and the outer membrane protein OmpA.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Healthy gilts and market-ready hogs were administered a single intramuscular (IM) injection of Borgal, a commercial formulation of trimethoprim-sulfadoxine (TMP-SDX), once or twice daily. The ...objectives were to determine if a newly-developed high-performance liquid chromatographic (HPLC) method would be suitable for measuring the residual concentrations of TMP in the plasma of these live animals, and to determine if the administration of this veterinary drug would leave measurable residues in their plasma and tissues at slaughter. Plasma and tissue concentrations of SDX and TMP from these animals were determined over a period of 14 d using thin-layer chromatography/densitometry (TLCD), and the newly-developed HPLC method, respectively. The lowest detectable limit (LDL) for SDX in plasma and tissue was 20 ppb by TLCD. The HPLC method had a LDL of 5 ppb for TMP in plasma and tissue. Both methods were then used to provide baseline data on the absorption and depletion of TMP and SDX from these healthy animals. It was observed that both TMP and SDX were readily absorbed into the blood and tissues, but TMP was eliminated much faster than SDX. No TMP residues were detected in the plasma of any of the gilts at and beyond 21 h after drug administration. Also, no TMP residues were detected in the plasma of any of the market-ready hogs 24 h after drug administration at either the label dose or twice the label dose. Sulfadoxine residues at concentrations above the maximum residue limit (MRL) of 100 ppb were, however, detected in the plasma, muscle, kidney, liver, and injection sites of hogs slaughtered 1 and 3 d after a single IM administration at the label dose. Although SDX residues were still detectable in the lungs, kidney, liver and plasma of some hogs 10 d after administration of the label dose and twice the label dose, these were below the MRL. Postmortem examination revealed necrosis and inflammation at the injection sites, but no visible deposits of the injected drug.
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