Design and methods of the REMOVAL-HD study: a tRial Evaluating Mid cut-Off Value membrane clearance of Albumin and Light chains in HaemoDialysis patients.

BACKGROUND: Removal of uraemic toxins is inadequate using current dialysis strategies. A new class of dialysis membranes have been developed that allow clearance of larger middle molecules. The REMOVAL-HD study (a tRial Evaluating Mid cut-Off Value membrane clearance of Albumin and Light chains in HaemoDialysis patients) will address safety, efficacy and the impact on patient-centred outcomes with the use of a mid cut-off (MCO) dialyser in a chronic haemodialysis (HD) population. METHODS: REMOVAL-HD is an open label, prospective, non-randomised, single-arm, multi-centre device study in 85 chronic HD participants. All visits will be conducted during regular HD sessions and participants will undergo a 1 month wash-in period using a standardised high flux dialyser, 6 months of intervention with a MCO dialyser and 1 month of wash-out using a high flux dialyser. The primary endpoint is change in pre-dialysis concentrations of serum albumin, with secondary endpoints including the efficacy of clearance of free light chains and ß-2 microglobulin, and patient-centred outcomes including quality of life, symptom burden, functional status, nutritional status, hospitalisation and death. DISCUSSION: MCO dialysers are a novel form of HD membrane. The REMOVAL-HD study is a pivotal study designed to monitor the immediate and medium-term effects following exposure to this dialyser. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry Number (ANZCTRN) 12616000804482 . Date of registration - 21/06/2016.

Uptake and Outcomes of Peritoneal Dialysis among Aboriginal and Torres Strait Islander People: Analysis of Registry Data.

Introduction: Peritoneal dialysis (PD) enables people to use kidney replacement therapy (KRT) outside of healthcare-dependent settings, a strong priority of Aboriginal and Torres Strait Islander people. Methods: We undertook an observational study analyzing registry data to describe access to PD and its outcome as the first KRT among Aboriginal and Torres Strait Islander people between January 1, 2004 and December 31 2020. Results: Out of 4604 Aboriginal and Torres Strait Islander people, reflecting 10.4% of all Australians commencing KRT, PD was the first KRT modality among 665 (14.4%). PD utilization was 17.2% in 2004 to 2009 and 12.7% in 2016 to 2020 (P = 0.002); 1105 episodes of peritonitis were observed in 413 individuals, median of 3 (interquartile range [IQR], 2-5) episodes/patient. The crude peritonitis rate was 0.53 (95% confidence interval [CI], 0.50-0.56) episodes/patient-years without any significant changes over time. The median time to first peritonitis was 1.1 years. A decrease in the peritonitis incidence rate ratio (IRR) was observed in 2016 to 2020 (IRR, 0.63 [95% CI, 0.52-0.77], P < 0.001) compared to earlier eras (2010-2015: IRR, 0.90 [95% CI, 0.76-1.07], P = 0.23; Ref: 2004-2009). The cure rates decreased from 80.0% (n = 435) in 2004 to 2009, to 70.8% (n = 131) in 2016 to 2020 (P < 0.001). Conclusion: Aboriginal and Torres Strait Islander people who utilized PD as their first KRT during 2004 to 2020 recorded a higher peritonitis rate than the current benchmark of 0.4 episodes/patient-years. The cure rates have worsened recently, which should be a big concern. There is an exigent need to address these gaps in kidney care for Aboriginal and Torres Strait Islander people.

Skin prick testing and peanut-specific IgE can predict peanut challenge outcomes in preschoolchildren with peanut sensitization.

BACKGROUND: The rise in peanut allergy is a source of considerable burden in the community. A growing number of preschoolchildren have been identified as peanut sensitized in the course of investigation of other allergic conditions. Although many have never knowingly ingested peanuts and their clinical reactivity is not known, it has been common practice to place these children on avoidance diets for many years. OBJECTIVE: To determine the utility of skin prick tests (SPT) and fluorescent-enzyme immunoassays (FEIA) for identifying either peanut allergy or tolerance in preschoolchildren with peanut sensitization. METHODS: Forty-nine preschoolchildren (<5 years of age) with peanut sensitization (SPT ≥ 2 mm or peanut-specific IgE ≥ 0.35 kU/L) but unknown clinical reactivity had graded open peanut challenges reaching a total of 11 g. A positive challenge was defined as an objective IgE-mediated reaction during challenge or the 2-h observation. RESULTS: Forty-nine percent (24/49) of children had positive challenges. An SPT of >7 mm on the day of challenge predicted a positive challenge with a sensitivity of 83% and a negative predictive value (NPV) of 84%. An FEIA of >2.0 kU/L showed a sensitivity of 79% and an NPV of 80%. Predicting challenge outcome from a combination of SPT and FEIA (SPT >7 and/or FEIA >2 is positive) increased sensitivity to 96% and NPV to 95%. CONCLUSION AND CLINICAL RELEVANCE: At least half of preschoolchildren with peanut sensitization and no antecedent history of peanut ingestion can tolerate peanuts. A SPT<7 mm and FEIA<2 kU/L identify children most likely to tolerate peanut, with only a 5% likelihood of failing an oral challenge. This study assists clinicians considering challenges in very young peanut-sensitized children.

Postoperative outcomes after bariatric surgery in patients on chronic dialysis: A systematic review and meta-analysis.

BACKGROUND: Obesity is a barrier to kidney transplantation for patients with kidney failure. Consequently, bariatric surgery is often considered as a bridge to transplantation, even though its risks and benefits are poorly characterised in the dialysis population. METHODS: Systematic searches of observational studies indexed in Embase, MEDLINE and CENTRAL till April 2020 were performed to identify relevant studies. Risk of bias was assessed by the Newcastle Ottawa Scale and quality of evidence was summarised in accordance with GRADE methodology. Random effects meta-analyses were performed to obtain summary odds ratios for postoperative outcomes. RESULTS: Four cohort studies involving 4196 chronic dialysis and 732,204 non-dialysis patients undergoing bariatric surgery were included. Sleeve gastrectomy (61%), and Roux-en-Y gastric bypass (29%) were the most common procedures performed. Absolute rates of adverse events were low, but the odds of postoperative mortality (0.4-0.5% vs. 0.1%; odds ratio [OR] 4.7, 95%CI 2.2-9.9), and myocardial infarction (0.0-0.5% vs. 0.1%, OR 3.4, 95% CI 2.0-5.9) were higher in dialysis compared to non-dialysis patients. Patients on dialysis also had more than 2-fold increased odds of returning to theatre and having a readmission. Rates of kidney transplant wait-listing among dialysis patients was 59%, with 28% of all patients eventually receiving a kidney transplant. CONCLUSION: Patients receiving chronic dialysis have substantially increased odds of postoperative mortality and myocardial infarction following bariatric surgery compared with patient who do not have kidney failure. It is uncertain whether bariatric surgery improves the likelihood of kidney transplantation, with mid- to long-term outcomes being poorly described.

Clinical and laboratory features of invasive community-onset methicillin-resistant Staphylococcus aureus infection: a prospective case-control study.

Differences between the features of invasive community-onset methicillin-resistant Staphylococcus aureus (cMRSA) and methicillin-susceptible S. aureus (cMSSA) infections are incompletely understood. Fifty-seven patients with invasive cMRSA infection were prospectively identified at two teaching hospitals; for each cMRSA case, two cases of invasive cMSSA infection acted as controls. The primary outcome was 30-day all-cause mortality. Patients with invasive cMRSA infection were more likely to be Aboriginal (25% vs. 14%, age-adjusted odds ratio [OR] 2.5, p = 0.037), reside in a long-term care facility and/or have been hospitalised in the previous year (51% vs. 34%, p = 0.04) and less likely to have endocarditis (2% vs. 12%, p = 0.02) or require admission to an intensive care unit or high-dependency area (7% vs. 21%, p = 0.02). All-cause mortality at 30 days was similar in the cMRSA and cMSSA groups (9% vs. 7%, p = 0.68). Panton-Valentine leukocidin (PVL) genes were detected in a similar proportion of cMRSA and cMSSA isolates (32% vs. 27%, p = 0.49) and the presence of PVL genes was associated with younger age (35 years vs. 55 years, p < 0.001), Aboriginal ethnicity (38% vs. 10%, p < 0.001), skin and soft-tissue infection (54% vs. 19%, p < 0.001), lower illness severity at presentation (SAPS II score 9 vs. 21, p = 0.001) and shorter hospitalisation (9 days vs. 24 days, p < 0.001). Patients with "PVL-positive" and "PVL-negative" S. aureus infection had similar 30-day all-cause mortality (4% vs. 9%, p = 0.28). Few clinical features differentiated patients with invasive cMRSA infection from those with infection caused by cMSSA. Invasive "PVL-positive" S. aureus infection was associated with less morbidity but similar mortality to "PVL-negative" infection.

Is atropine needed with ketamine sedation? A prospective, randomised, double blind study.

OBJECTIVE: To compare atropine with placebo as an adjunct to ketamine sedation in children undergoing minor painful procedures. Outcome measures included hypersalivation, side effect profile, parental/patient satisfaction, and procedural success rate. METHODS: Children aged between 1 and 16 years of age requiring ketamine procedural sedation in a tertiary emergency department were randomised to receive 0.01 mg/kg of atropine or placebo. All received 4 mg/kg of intramuscular ketamine. Tolerance and sedation scores were recorded throughout the procedure. Side effects were recorded from the start of sedation until discharge. Parental and patient satisfaction scores were obtained at discharge and three to five days after the procedure, with the opportunity to report side effects encountered at home. RESULTS: A total of 83 patients aged 13 months to 14.5 years (median age 3.4 years) were enrolled over a 16 month period. Hypersalivation occurred in 11.4% of patients given atropine compared with 30.8% given placebo (odds ratio (OR) 0.29, 95% confidence interval (CI) 0.09 to 0.91). A transient rash was observed in 22.7% of the atropine group compared with 5.1% of the placebo group (OR 5.44, 95% CI 1.11 to 26.6). Vomiting during recovery occurred in 9.1% of atropine patients compared with 25.6% of placebo patients (OR 0.29, 95% CI 0.09 to 1.02). There was a trend towards better tolerance in the placebo group. No patient experienced serious side effects. CONCLUSION: Ketamine sedation was successful and well tolerated in all cases. The use of atropine as an adjunct for intramuscular ketamine sedation in children significantly reduces hypersalivation and may lower the incidence of post-procedural vomiting. Atropine is associated with a higher incidence of a transient rash. No serious adverse events were noted.

Intranasal fentanyl is an equivalent analgesic to oral morphine in paediatric burns patients for dressing changes: a randomised double blind crossover study.

INTRODUCTION: The ideal analgesic agent for burns wound dressings in paediatric patients would be one that is easy to administer, well tolerated, and produces rapid onset of analgesia with a short duration of action and minimal side-effects to allow rapid resumption of activities and oral intake. We compared our current treatment of oral morphine to intranasal fentanyl in an attempt to find an agent closer to the ideal. METHODS: A randomised double blind two-treatment crossover study comparing intranasal administration of fentanyl (INF) to orally administered morphine (OM). Children with burn injury aged up to 15 years and weighing 10-75 kg were included. Primary end-point was pain scores. Secondary end-points were time to resumption of age-appropriate activities, time to resumption of fluid intake, sedation and cooperation. Routine observations and vital signs were also recorded. RESULTS: Twenty-four patients were studied with a median age of 4.5 years (interquartile range 1.8-9.0 years) and a median weight of 18.4 kg (interquartile range 12.9-33.2kg). Mean pain difference scores (OM-INF) ranged from -0.500 (95% CI=-1.653 to 0.653) at baseline to -0.625 (05% CI=-1.863 to 0.613) for a retrospective rating of worst pain experienced during the dressing procedure. All measurements were within a pre-defined range of equivalent efficacy. The median time to resumption of fluid intake was 108 min (range 44-175 min) with OM and 140 min (range 60-210 min) with INF. These differences were not statistically significant. Fewer patients experienced mild side-effects with INF compared to OM (n=5 versus n=10). No patients experienced depressed respirations or oxygen saturations. SUMMARY: Intranasal fentanyl was shown to be equivalent to oral morphine in the provision of analgesia for burn wound dressing changes in this cohort of paediatric patients. It was concluded that intranasal fentanyl is a suitable analgesic agent for use in paediatric burns dressing changes either by itself or in combination with oral morphine as a top up titratable agent.

Home oxygen for children with acute bronchiolitis.

A prospective randomised controlled pilot study was performed comparing home oxygen therapy with traditional inpatient hospitalisation for children with acute bronchiolitis. Children aged 3-24 months with acute bronchiolitis, still requiring oxygen supplementation 24 h after admission to hospital, were randomly assigned to receive oxygen supplementation at home with support from "hospital in the home" (HiTH) or to continue oxygen supplementation in hospital. 44 children (26 male, mean age 9.2 months) were recruited (HiTH n = 22) between 1 August and 30 November 2007. Only one child from each group was readmitted to hospital and there were no serious complications. Children in the HiTH group spent almost 2 days less in a hospital bed than those managed as traditional inpatients: HiTH 55.2 h (interquartile range (IQR) 40.3-88.9) versus in hospital 96.9 h (IQR 71.2-147.2) p = 0.001. Home oxygen therapy appears to be a feasible alternative to traditional hospital oxygen therapy in selected children with acute bronchiolitis.

Predictors of response to bronchial allergen challenge in 5- to 6-year-old atopic children.

BACKGROUND: The relationship between atopy and bronchial allergy in young children is not completely understood. OBJECTIVE: To examine the association between response to bronchial allergen challenge, immune markers of atopy and other clinical characteristics in 5- to 6-year-old children. METHODS: Children with positive skin test (SPT) to aeroallergen, together with a proportion of SPT negative children (as controls), were recruited from a birth cohort of 198 children at high risk of developing atopic disease and underwent allergen challenge. RESULTS: Thirty-seven children (26 atopic and 11 SPT negative), median age 74.5 months, were challenged: 31 with house dust mite and six with grass allergen. Only atopic children responded to challenge: n = 12/26 (46%). Wheal size [odds ratio (OR) 2.5 (1.2-5.3), P = 0.01], allergen-specific immunoglobulin E (IgE) [OR 3.4 (1.23-9.61), P = 0.02], total IgE [OR 8.6 (1.1-68.7), P = 0.04], current wheeze [OR 12 (1.7-81.7), P = 0.006] and persistent eczema [OR 11.0 (1.7-68.3), P = 0.006] emerged as the strongest independent predictors of response to allergen challenge. Prediction of response to allergen challenge was significantly improved when immune markers of atopy, and in particular wheal size, were combined with clinical characteristics. CONCLUSION: The relationship between atopy and bronchial allergy is quantitative at this age. There may be potential to create more powerful indicators of the presence of respiratory allergy in young children when immunological markers of atopy are considered quantitatively and when combined with clinical history of coexistent allergic disease.