BACKGROUND:Children with medical complexity (CMC) represent a small, but growing, proportion of all children. Regardless of their underlying diagnosis, by definition, all CMC have similar functional limitations and high healthcare needs. It has been suggested that improving aspects of healthcare delivery for CMC improves health- and quality of life-related outcomes for children and their families and reduces healthcare-related expenditure. As a result, dedicated comprehensive care programmes have been established at many hospitals to meet the needs of CMC; however, it is unclear if such programmes are effective. OBJECTIVES:Our main objective was to assess the effectiveness of comprehensive care programmes that aim to improve care coordination and other aspects of health care for CMC and to assess whether the effectiveness of such programmes differs according to the programme setting and structure. We aimed to assess their effectiveness in relation to child and parent health, functioning, and quality of life, quality of care, number of healthcare encounters, unmet healthcare needs, and total healthcare-related costs. SEARCH METHODS:We searched CENTRAL, MEDLINE, Embase, and CINAHL in May 2023. We also searched reference lists, trial registries, and the grey literature. SELECTION CRITERIA:Randomised and non-randomised trials, controlled before-after studies, and interrupted time series studies were included. Studies that compared enrolment in a comprehensive care programme with non-enrolment in such a programme/treatment as usual were included. Participants were children that met the criteria for the definition of CMC, which is: having (i) a chronic condition, (ii) functional limitations, (iii) increased health and other service needs, and (iv) increased healthcare costs. Studies that included the following types of outcomes were included: health; quality of care; utilisation, coverage and access; resource use and costs; equity; and adverse outcomes. DATA COLLECTION AND ANALYSIS:Two review authors independently extracted data, assessed the risk of bias in each included study, and evaluated the certainty of evidence according to GRADE criteria. Where possible, data were represented in forest plots and pooled. We were unable to undertake a meta-analysis for comparisons and outcomes, so we used a structured synthesis approach. MAIN RESULTS:We included four studies with a total of 912 CMC as participants. All included studies were randomised controlled trials conducted in hospitals in the USA or Canada. Participants varied across the included studies; however, all four studies included children with complex and chronic illness and high healthcare needs. While the primary aim of the intervention was similar across all four studies, the components of the interventions differed: in the four studies, the intervention involved some element of care coordination; in two of the studies, it involved the child receiving care from a multidisciplinary team, while in one study, the intervention was primarily centred on access to an advanced practice nurse care coordinator and another study involved nurse a practitioner-paediatrician dyad partnering with families. The risk of bias in the four studies varied across domains, with issues primarily relating to the lack of blinding of participants, personnel, and outcome assessors, inadequate allocation concealment, and incomplete outcome data. Comprehensive care for CMC compared to usual care may make little to no difference to child health, functioning, and quality of life at 12 or 24 months (three studies with 404 participants) and we assessed the evidence for the outcomes in this category (child health-related quality of life and functional status) as being of low certainty. For CMC, comprehensive care probably makes little or no difference to parent health, functioning, and quality of life compared to usual care at 12 months (one study with 117 participants) and we assessed the evidence for this outcome as being of moderate certainty. Comprehensive care for CMC compared to usual care may slightly improve child and family satisfaction with, and perceptions of, care and service delivery at 12 months (three studies with 453 participants); however, we assessed the evidence for these outcomes as being of low certainty. For CMC, comprehensive care probably makes little or no difference to the number of healthcare encounters (emergency department visits) and the number of hospitalised days (hospital admissions) compared to usual care at 12 months (three studies with 668 participants), and we assessed the evidence for these outcomes as being of moderate certainty. Three of the included studies (668 participants) reported cost outcomes and had conflicting results, with one study reporting significantly lower healthcare costs at 12 months in the intervention group compared to the control group, one reporting no differences between groups, and the other study reporting a greater increase in total healthcare costs in the intervention group compared to the control group. Overall, comprehensive care may make little or no difference to overall healthcare costs in CMC; however, the methods used to measure total healthcare costs varied across studies and the certainty of the evidence relating to this outcome is low. No studies assessed the costs to the family. AUTHORS' CONCLUSIONS:The findings of this review should be treated with caution due to the limited amount and quality of the published research that was available to be included. Overall, the certainty of the evidence for the effectiveness of comprehensive care for CMC ranged from low to moderate across outcomes and there is currently insufficient evidence on which to draw strong conclusions. There is a need for more high-quality randomised trials with consistency of the target population and intervention components, methods of reporting outcomes, and follow-up periods, as well as full cost analyses, taking into account both costs to the family and costs to the healthcare system.

BACKGROUND:In settings with universal conjugate pneumococcal vaccination, invasive pneumococcal disease (IPD) can be a marker of an underlying inborn error of immunity. The aim of this study was to determine the prevalence and characterize the types of immunodeficiencies in children presenting with IPD.METHODS:Multicenter prospective audit following the introduction of routinely recommended immunological screening in children presenting with IPD. The minimum immunological evaluation comprised a full blood examination and film, serum immunoglobulins (IgG, IgA and IgM), complement levels and function. Included participants were children in whom Streptococcus pneumoniae was isolated from a normally sterile site (cerebrospinal fluid, pleura, peritoneum and synovium). If isolated from blood, features of sepsis needed to be present. Children with predisposing factors for IPD (nephrotic syndrome, anatomical defect or malignancy) were excluded.RESULTS:Overall, there were 379 episodes of IPD of which 313 (83%) were eligible for inclusion and 143/313 (46%) had an immunologic evaluation. Of these, 17/143 (12%) were diagnosed with a clinically significant abnormality: hypogammaglobulinemia (n = 4), IgA deficiency (n = 3), common variable immunodeficiency (n = 2), asplenia (n = 2), specific antibody deficiency (n = 2), incontinentia pigmenti with immunologic dysfunction (n = 1), alternative complement deficiency (n = 1), complement factor H deficiency (n = 1) and congenital disorder of glycosylation (n = 1). The number needed to investigate to identify 1 child presenting with IPD with an immunologic abnormality was 7 for children under 2 years and 9 for those 2 years old and over.CONCLUSIONS:This study supports the routine immune evaluation of children presenting with IPD of any age, with consideration of referral to a pediatric immunologist.

Background Australian immigration policy resulted in large numbers of children being held in locked detention. We examined the physical and mental health of children and families who experienced immigration detention. Methods Retrospective audit of medical records of children exposed to immigration detention attending the Royal Children’s Hospital Immigrant Health Service, Melbourne, Australia, from January 2012 –December 2021. We extracted data on demographics, detention duration and location, symptoms, physical and mental health diagnoses and care provided. Results 277 children had directly (n = 239) or indirectly via parents (n = 38) experienced locked detention, including 79 children in families detained on Nauru or Manus Island. Of 239 detained children, 31 were infants born in locked detention. Median duration of locked detention was 12 months (IQR 5–19 months). Children were detained on Nauru/Manus Island (n = 47/239) for a median of 51 (IQR 29–60) months compared to 7 (IQR 4–16) months for those held in Australia/Australian territories (n = 192/239). Overall, 60% (167/277) of children had a nutritional deficiency, and 75% (207/277) had a concern relating to development, including 10% (27/277) with autism spectrum disorder and 9% (26/277) with intellectual disability. 62% (171/277) children had mental health concerns, including anxiety, depression and behavioural disturbances and 54% (150/277) had parents with mental illness. Children and parents detained on Nauru had a significantly higher prevalence of all mental health concerns compared with those held in Australian detention centres. Conclusion This study provides clinical evidence of adverse impacts of held detention on children’s physical and mental health and wellbeing. Policymakers must recognise the consequences of detention, and avoid detaining children and families.

We present the case of a 2-year-old immunocompetent boy who presented with subacute right-sided orbital cellulitis due to Saksaenea vasiformis infection. Initial differential diagnoses included chalazion and localized soft tissue malignancy. There was no history of trauma. Immunological review and investigations were unremarkable. He was treated with a total of 3 months of antifungal therapy. Following resolution, he had two episodes of spontaneously resolving localized eyelid erythema at 2 and 8 months.

Background. Prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) is effective, but outcome information beyond the postnatal period in low-prevalence settings is scarce. A multidisciplinary model of care (MOC) was developed to ensure PMTCT. Our aims in this study were to assess how well HIV-exposed infants are followed up through this MOC and to determine infant outcomes to age 18 months. Methods. This was a multicenter, prospective study of infants exposed to HIV during pregnancy, born 1 September 2009-31 August 2016 in Victoria, Australia. Results. There were 129 live births from 127 pregnancies. There were no episodes of HIV transmission. Sixteen (13%) infants were born prematurely, 15 (12%) had low birthweight, and 6 (5%) had a congenital anomaly. There were 122 (95%) infants with an HIV polymerase chain reaction (PCR) within 2 weeks of birth. The proportion in the MOC reduced from 95% at 2 weeks postnatally to 75% by 18 months. Eighty-eight percent cared for within the MOC had 2 viral PCR tests completed after stopping antiretroviral prophylaxis compared with 22% of those outside of the MOC. By 18 months, 84/126 (67%) children attended follow-up, with higher rates within the MOC than outside (76% vs 6%; odds ratio, 46; 95% confidence interval, 6 to 365; P<.001). Conclusions. HIV-exposed, uninfected infants in this low-prevalence setting had good prospective follow-up through this MOC to 3 months. The decrease in follow-up by 18 months could be addressed in several ways, including expanding the MOC and providing better links to regional/rural services.

Background: Current immune-based TB tests, including the tuberculin skin test (TST) and interferon-gamma release assays (IGRA), have significant limitations, including the inability to distinguish between latent TB infection (LTBI) and active TB. Few biomarkers with the potential to discriminate between these two infection states have been identified. Objective: To determine whether functional profiling of mycobacteria-specific T cells can distinguish between TB-infected and -uninfected children, and simultaneously discriminate between LTBI and active TB. Methods: One hundred and forty-nine children with suspected active TB or risk factors for LTBI were recruited at the Royal Children's Hospital Melbourne. Whole-blood stimulation assays, using ESAT-6, CFP-10, PPD, and heat-killed M. tuberculosis as stimulants, were done, followed by intracellular cytokine staining and flow cytometric analysis. Results: Eighty-two participants in the well-defined diagnostic categories ‘uninfected individuals’ (asymptomatic, TST 0 mm / IGRA-; n = 61), LTBI (asymptomatic, TST ≥10 mm / IGRA+, normal chest radiograph; n = 15), or active TB [microbiologically-confirmed (n = 3) or fulfilling stringent criteria (n = 3)] were included in the final analysis. The proportions of mycobacteria-specific single-positive TNF-α+ and double-positive IFN-γ+/TNF-α+ CD4+ T cells were significantly higher in participants with active TB than in those with LTBI and uninfected individuals. Additionally, the frequency of IL-17-expressing CD4+ T cells, predominately with single-positive IL-17+ and double-positive IL-2+/IL-17+ phenotypes, was higher in participants with active TB than in the other two groups. Conclusions: The frequencies and functional profiles of mycobacteria-specific CD4+ T cells differ significantly both between TB-infected and TB-uninfected children, and between LTBI and active TB. Although confirmation in further studies will be required, these findings indicate that functional profiling of mycobacteria-specific CD4+ T cells could potentially be exploited for novel immune-based TB assays that enable the distinction between infection states based on a blood sample alone.

The treatment of Mycobacterium abscessus complex (MABSC) pulmonary infections is an emerging challenge in patients with cystic fibrosis (CF). Multidrug therapy for prolonged durations is required and carries the significant burden of drug‐related toxicity, cost and selective pressure for multiresistant bacteria. International guidelines acknowledge that clinical and in vitro data to support treatment regimens are limited, particularly in children. As part of a collaboration between the infectious diseases and respiratory units at our institution, we have developed a modified treatment guideline that aims to balance the aims of MABSC eradication and slowing disease progression with minimising drug toxicity and resistance. The outcomes of this treatment approach will be monitored and reported. In this manuscript, we discuss the available evidence for treatment choices and present our treatment guideline for paediatric patients with CF and MABSC infection.

BACKGROUND:Ward rounds are a fundamental part of hospital culture and teaching on rounds has a long tradition. Yet evidence points towards increasing difficulties in delivering ward round education in complex heath care settings. Drawing on the literature and gaps identified in our own hospital setting we hypothesised that a tool for structuring ward rounds could improve the educational experience on rounds without adding a time burden to already busy consultants. METHODS:We used a developmental evaluation approach to develop a framework and evaluate a tool for improving ward round education. The ward round framework STIC (Set, Target, Inspect and Close) and ward round tool was developed through an iterative process of reviewing and piloting in a clinical department and was evaluated against Moore's outcome levels drawing on quantitative and qualitative data. Surveys of consultants were used to quantify uptake, acceptability and usefulness of the ward round tool. Focus groups of trainee doctors evaluated their experience of ward round education. RESULTS:The majority of consultants used the ward round tool and found it accessible, and useful to enhance education, without extending ward round time. Trainee doctors had seen the ward round tool in use and reflected that it provided structure, focused their learning opportunities, gave clarity to the agenda and provided closure. Unintended benefits were seen for enhanced team work. CONCLUSIONS:We present a structured framework STIC and tool for ward rounds that incorporates education, which is acceptable to consultants and is perceived to enhance education for trainees and to strengthen team work. Understanding our framework STIC and our ward round tool's applicability in other settings, scalability and impact and the perspective of patients, would be valuable extensions of this work. We present a structured framework STIC and tool for ward rounds that incorporates education, which is acceptable to consultants and is perceived to enhance education for trainees and to strengthen team work.

The treatment of Mycobacterium abscessus complex (MABSC) pulmonary infections is an emerging challenge in patients with cystic fibrosis (CF). Multidrug therapy for prolonged durations is required and carries the significant burden of drug-related toxicity, cost and selective pressure for multiresistant bacteria. International guidelines acknowledge that clinical and in vitro data to support treatment regimens are limited, particularly in children. As part of a collaboration between the infectious diseases and respiratory units at our institution, we have developed a modified treatment guideline that aims to balance the aims of MABSC eradication and slowing disease progression with minimising drug toxicity and resistance. The outcomes of this treatment approach will be monitored and reported. In this manuscript, we discuss the available evidence for treatment choices and present our treatment guideline for paediatric patients with CF and MABSC infection.

We thank Eric McGrath and colleagues1McGrath E Abdel-Haq N Asmar B Chu R Rajpurkar M Ethanol lock for CLABSI in children with cancer: a matter of (dwell) time?.Lancet Infect Dis. 2018; 18: 1067-1068Summary Full Text Full Text PDF PubMed Scopus (2) Google Scholar for their Correspondence in relation to our randomised controlled trial of ethanol lock therapy for treatment and secondary prophylaxis of central line-associated bloodstream infection in children with cancer.2Wolf J Connell TG Allison KJ et al.Treatment and secondary prophylaxis with ethanol lock therapy for central line-associated bloodstream infection in paediatric cancer: a randomised, double-blind, controlled trial.Lancet Infect Dis. 2018; 18: 854-863Summary Full Text Full Text PDF PubMed Scopus (32) Google Scholar McGrath and colleagues1McGrath E Abdel-Haq N Asmar B Chu R Rajpurkar M Ethanol lock for CLABSI in children with cancer: a matter of (dwell) time?.Lancet Infect Dis. 2018; 18: 1067-1068Summary Full Text Full Text PDF PubMed Scopus (2) Google Scholar suggest our finding that ethanol lock therapy did not improve infection outcomes (while significantly increasing the risk of catheter occlusion) might be explained by insufficient dwell time. They propose that the use of dwell times longer than 2–4 h could be effective. Whereas our study does not preclude this possibility, the available data do not support this hypothesis. Although the in-vitro study by Peters and colleagues,3Peters BM Ward RM Rane HS Lee SA Noverr MC Efficacy of ethanol against Candida albicans and Staphylococcus aureus polymicrobial biofilms.Antimicrob Agents Chemother. 2013; 57: 74-82Crossref PubMed Scopus (88) Google Scholar which is referred to in the Correspondence, suggested that exposure to ethanol for 4 h was effective for biofilm eradication, they used a lower concentration of ethanol and did not compare this with a 2 h exposure. By contrast, several studies evaluating the effect of clinically relevant concentrations of ethanol have shown that maximal killing of susceptible biofilm bacteria occurs within 2 h.4Wolf J Shenep JL Clifford V Curtis N Flynn PM Ethanol lock therapy in pediatric hematology and oncology.Pediatr Blood Cancer. 2013; 60: 18-25Crossref PubMed Scopus (37) Google Scholar, 5Shenep LE Shenep MA Cheatham W et al.Efficacy of intravascular catheter lock solutions containing preservatives in the prevention of microbial colonization.J Hosp Infect. 2011; 79: 317-322Summary Full Text Full Text PDF PubMed Scopus (23) Google Scholar The in-vitro study by Shenep and colleagues5Shenep LE Shenep MA Cheatham W et al.Efficacy of intravascular catheter lock solutions containing preservatives in the prevention of microbial colonization.J Hosp Infect. 2011; 79: 317-322Summary Full Text Full Text PDF PubMed Scopus (23) Google Scholar did find that 2 h of ethanol exposure did not eradicate mature biofilms of Bacillus cereus. This finding is unsurprising as B cereus is known to be alcohol-resistant.6Dolan SA Dowell E Littlehorn C Glode MP Todd JK Notes from the field: contamination of alcohol prep pads with Bacillus cereus group and Bacillus species—Colorado, 2010.MMWR Morb Mortal Wkly Rep. 2011; 60: 347PubMed Google Scholar No cases of infection with B cereus were included in our study. The two clinical studies of ethanol lock therapy by McGrath and colleagues1McGrath E Abdel-Haq N Asmar B Chu R Rajpurkar M Ethanol lock for CLABSI in children with cancer: a matter of (dwell) time?.Lancet Infect Dis. 2018; 18: 1067-1068Summary Full Text Full Text PDF PubMed Scopus (2) Google Scholar report high rates of success with ethanol lock therapy dwell times of 4–24 h. However, in the absence of a non-ethanol lock therapy control arm, these findings need to be interpreted with caution. To date, there remain no published comparative studies that show ethanol lock therapy is effective as treatment or secondary prophylaxis for central line-associated blood- stream infection except in patients undergoing dialysis.2Wolf J Connell TG Allison KJ et al.Treatment and secondary prophylaxis with ethanol lock therapy for central line-associated bloodstream infection in paediatric cancer: a randomised, double-blind, controlled trial.Lancet Infect Dis. 2018; 18: 854-863Summary Full Text Full Text PDF PubMed Scopus (32) Google Scholar, 4Wolf J Shenep JL Clifford V Curtis N Flynn PM Ethanol lock therapy in pediatric hematology and oncology.Pediatr Blood Cancer. 2013; 60: 18-25Crossref PubMed Scopus (37) Google Scholar We caution against continuing as normal considering the evidence from our double-blind, randomised, placebo-controlled trial. Given the absence of comparative data that supports efficacy of ethanol lock therapy as treatment for central line-associated bloodstream infection in patients not on dialysis, and the evidence it can cause serious harm, we recommend that clinicians avoid routine use of this treatment outside of well designed prospective clinical trials. We declare no competing interests. Ethanol lock for CLABSI in children with cancer: a matter of (dwell) time?We read with interest the Article by Joshua Wolf and colleagues about treatment and secondary prophylaxis with ethanol lock for central-line associated bloodstream infection (CLABSI) in children with cancer.1 The results of their 5-year study suggest that ethanol lock therapy, used in treatment and as secondary prophylaxis in this population, is not effective. In the study, patients with cancer who had new CLABSI were treated with systemic antimicrobials and randomly assigned to receive 70% ethanol lock therapy for 2–4 h for 5 days or heparin locks (placebo). Full-Text PDF Treatment and secondary prophylaxis with ethanol lock therapy for central line-associated bloodstream infection in paediatric cancer: a randomised, double-blind, controlled trialEthanol lock therapy did not prevent CLABSI treatment failure and it increased catheter occlusion. Routine ethanol lock therapy for treatment or secondary prophylaxis is not recommended in this population. Full-Text PDF

Splenic complications of invasive meningococcal disease (IMD) are well recognised, though cyst formation is rare, particularly in paediatric populations. The best approach to their management is not yet established. This case outlines the management of a splenic cyst in a 21-month-old boy following severe IMD. The case took place in the context of an acute emergence of serogroup W prompting significant media attention and subsequent change in vaccination practice at a jurisdictional level in Australia. The patient was critically unwell early in the illness, then later a collection in the left upper quadrant was detected, shown on ultrasound to be a 11.6×7.7 cm splenic cyst. In this case, the cyst was managed by ultrasound-guided drainage tube insertion. The residual collection was small and stable on subsequent imaging.

Background Central line-associated bloodstream infections (CLABSIs) affect about 25% of children with cancer, and treatment failure is common. Adjunctive ethanol lock therapy might prevent treatment failure but high-quality evidence is scarce. We evaluated ethanol lock therapy as treatment and secondary prophylaxis for CLABSI in children with cancer or haematological disorders. Methods This randomised, double-blind, placebo-controlled superiority trial, with two interim futility and efficacy analyses (done when the first 46 and 92 evaluable participants completed study requirements), was done at two paediatric hospitals in the USA and Australia. Patients aged 6 months to 24 years, inclusive, with cancer or a haematological disorder and new CLABSI were eligible. Participants were randomly assigned (1: 1) to receive either ethanol lock therapy (70% ethanol) or placebo (heparinised saline) for 2-4 h per lumen daily for 5 days (treatment phase), then for up to 3 non-consecutive days per week for 24 weeks (prophylaxis phase). The primary composite outcome was treatment failure, consisting of attributable catheter removal or death, new or persistent (> 72 h) infection, or additional lock therapy during the treatment phase, and recurrent CLABSI during the prophylaxis phase. This trial is registered with ClinicalTrials.gov, number NCT01472965. Findings 94 evaluable participants were enrolled between Dec 14, 2011, and Sept 12, 2016, of whom 48 received ethanol lock therapy and 46 received placebo. The study met futility criteria at the second interim analysis. Treatment failure was similar with ethanol lock therapy (21 [44%] of 48) and placebo (20 [43%] of 46; relative risk [RR] 1.0, 95% CI 0.6-1.6; p=0.98). Some adverse events, including infusion reactions and catheter occlusion, were more frequent in the ethanol lock therapy group than in the placebo group. Catheter occlusion requiring thrombolytic therapy was more common with ethanol lock therapy (28 [58%] of 48) than with placebo (15 [33%] of 46; RR 1.8, 95% CI 1.1-2.9; p=0.012). Discontinuation of lock therapy because of adverse effects or patient request occurred in a similar proportion of participants in the ethanol lock therapy (nine [19%] of 48) and placebo groups (ten [22%] of 46; p=0.72). Interpretation Ethanol lock therapy did not prevent CLABSI treatment failure and it increased catheter occlusion. Routine ethanol lock therapy for treatment or secondary prophylaxis is not recommended in this population. Copyright (c) 2018 Elsevier Ltd. All rights reserved.

Objective Children with moderate/severe cellulitis requiring intravenous antibiotics are usually admitted to hospital. Admission avoidance is attractive but there are few data in children. We implemented a new pathway for children to be treated with intravenous antibiotics at home and aimed to describe the characteristics of patients treated on this pathway and in hospital and to evaluate the outcomes. Methods This is a prospective, observational cohort study of children aged 6 months–18 years attending the ED with uncomplicated moderate/severe cellulitis in March 2014–January 2015. Patients received either intravenous ceftriaxone at home or intravenous flucloxacillin in hospital based on physician discretion. Primary outcome was treatment failure defined as antibiotic change within 48 hours due to inadequate clinical improvement or serious adverse events. Secondary outcomes include duration of intravenous antibiotics and complications. Results 115 children were included: 47 (41%) in the home group and 68 (59%) in the hospital group (59 hospital-only, 9 transferred home during treatment). The groups had similar clinical features. 2/47 (4%) of the children in the home group compared with 8/59 (14%) in the hospital group had treatment failure (P=0.10). Duration of intravenous antibiotics (median 1.9 vs 1.8 days, P=0.31) and complications (6% vs 10%, P=0.49) were no different between groups. Home treatment costs less, averaging $A1166 (£705) per episode compared with $A2594 (£1570) in hospital. Conclusions Children with uncomplicated cellulitis may be able to avoid hospital admission via a home intravenous pathway. This approach has the potential to provide cost and other benefits of home treatment.

Background: Despite the benefits of home treatment with outpatient parenteral antimicrobial therapy (OPAT), children with pyelonephritis and meningitis are rarely included. We aimed to compare clinical characteristics and outcomes between hospital and home treatment for these conditions and to identify factors influencing home treatment.Methods: Children admitted to the hospital with pyelonephritis or proven and presumed bacterial meningitis from January 1, 2012, to December 31, 2013 were identified retrospectively. Patients who received any OPAT (home group) received daily visits via our Hospital-in-the-Home (HITH) program; inpatients (hospital group) received standard care. Clinical and demographic features, length of stay, readmission rate and cost were compared between hospital and home groups.Results: One hundred thirty-nine children with pyelonephritis and 70 with meningitis were identified, of which 127 and 44 were potentially suitable for OPAT, respectively. Of these, 12 (9%) with pyelonephritis received OPAT, contrasting with 29 (66%) with meningitis. Clinical features did not differ between hospital-and home-treated patients for either condition. Patients with meningitis in the hospital group were younger than those transferred to HITH (1 vs. 2 months; P = 0.01). All patients were afebrile before transfer to HITH. Admissions for pyelonephritis were brief with inpatients having a shorter length of stay than home patients (median: 3 vs. 4.5 days; P = 0.002). Unplanned readmission rates were comparable across all groups. Transfer to HITH resulted in a saving of AU$178,180.Conclusions: Children with pyelonephritis and meningitis can feasibly receive OPAT. Age, treatment duration and fever influence this decision. None of these should be barriers to OPAT, and the cost savings support change in practice.

Abstract Background Central line-associated bloodstream infection (CLABSI) commonly affects children with cancer and hematological disorders, with significant attributable costs and morbidity. Treatment failure, comprising persistent infection, infection relapse or new infection, occurs in ~50% of cases. Adjunctive ethanol lock therapy (ELT) has been proposed to prevent failure, but has never been tested in a prospective controlled study. Methods A prospective, dual-center, double-blind, block-randomized, placebo-controlled trial of ELT (70% ethanol in water) for CLABSI, given as treatment (2 hours per lumen per day) for 5 days, followed by secondary prophylaxis (2 hours per lumen up to 3 days per week) for 24 weeks, in children with oncologic or hematologic disorders (NCT01472965). Risk of treatment failure was compared between intervention and control groups according to proportional and cumulative incidence models, using intention-to-treat and per-protocol analyses. The study was discontinued at a pre-specified futility analysis. Results Of 94 evaluable participants, 48 were randomized to ELT and 46 to placebo; groups were similar at baseline for all measured variables. Forty-one (43.6%) participants had treatment failure (11 early failure, 9 relapse, and 21 reinfection). There was no difference between patients receiving ELT or placebo for risk of treatment failure (43.8% vs. 43.5%; P = 0.9) or for cumulative incidence of treatment failure in intention to treat (Figure 1) and per-protocol analyses (Figure 2). Catheter occlusion was significantly more common in participants receiving ethanol (58.3% vs. 32.6%, P = 0.01) but other adverse events, including LFT elevations (14.6% vs. 26.1%) and infusion reactions (18.8% vs. 8.7%), were not significantly different between groups. Conclusion Although observational studies suggested ELT might be effective for treatment of CLABSI in pediatric oncology, we found no benefit in treatment outcome and an increase in adverse effects. These results may not apply to patients receiving dialysis or with fungal CLABSI as these were not well-represented. Routine use of ELT for CLABSI in children with oncologic or hematologic disorders is not recommended. Disclosures All authors: No reported disclosures.

BACKGROUND:More than 120 million doses of BCG vaccine are administered worldwide each year. Most infants are given BCG at birth in accordance with WHO recommendations. However, the effect of the maturing neonatal immune system on the immune response and protection conferred by BCG remains uncertain. Previous studies investigating the influence of age at immunisation on the immune response induced by BCG have reported conflicting results. This study compared BCG given at birth and at two months of age in infants in Australia. METHODS:Infants born in Melbourne were randomly allocated to immunisation with BCG-Denmark at birth or two months of age. Ten weeks after immunisation, anti-mycobacterial immune responses were measured in a whole blood assay using intracellular cytokine assays and xMAP multiplex cytokine analysis. RESULTS:Result from 98 BCG-immunised infants were included in the final analysis. BCG immunisation at birth (n=54) and at 2months of age (n=44) induced comparable proportions of mycobacteria-specific cytokine-producing CD4 and CD8 T cells, as well as comparable proportions of polyfunctional (TNF(+) IL-2(+) IFN-γ(+)) CD4 T cells. Concentrations of cytokines in supernatants were also similar in both groups. CONCLUSIONS:Cellular immunity measured 10weeks after BCG immunisation was similar in infants given BCG at birth and in those given BCG at 2months of age. Although definitive correlates of protection against TB remain uncertain, these results suggest that delaying BCG immunisation does not confer any immunological advantage in cellular immunity.

7 1 Department of Paediatrics, The University of Melbourne; and Infectious Diseases 8 Unit, Royal Children’s Hospital Melbourne, Parkville, Australia 9 2 Infectious Diseases and Microbiology Group, Murdoch Children’s Research 10 Institute, Royal Children’s Hospital, Australia 11 3 University of Basel Children’s Hospital Basel, Infectious Diseases Unit and 12 Paediatric Pharmacology, Basel, Switzerland; 13 4 Department of Paediatrics, The Mercy Hospital for Women, Heidelberg, Australia 14 5 Clinical Epidemiology and Biostatistics Unit, Murdoch Children's Research Institute; 15 Royal Children's Hospital Melbourne, Parkville, Australia 16 6 Academic Unit of Clinical & Experimental Sciences, Faculty of Medicine, and 17 Institute for Life Sciences, University of Southampton, Southampton, UK 18 7 Department of Microbiology and Immunology, The University of Melbourne at the 19 Peter Doherty Institute for Infection and Immunity; 20

BACKGROUND:There are limited data on the epidemiology, diagnosis and optimal management of nontuberculous mycobacterial (NTM) disease in children.METHODS:Retrospective cohort study of NTM cases over a 10-year-period at a tertiary referral hospital in Australia.RESULTS:A total of 140 children with NTM disease, including 107 with lymphadenitis and 25 with skin and soft tissue infections (SSTIs), were identified. The estimated incidence of NTM disease was 0.6-1.6 cases / 100,000 children / year; no increasing trend was observed over the study period. Temporal analyses revealed a seasonal incidence cycle around 12 months, with peaks in late winter/spring and troughs in autumn. Mycobacterium-avium-complex accounted for most cases (77.8%), followed by Mycobacterium ulcerans (14.4%) and Mycobacterium marinum (3.3%). Polymerase chain reaction testing had higher sensitivity than culture and microscopy for acid-fast bacilli (92.0%, 67.2% and 35.7%, respectively). The majority of lymphadenitis cases underwent surgical excision (97.2%); multiple recurrences in this group were less common in cases treated with clarithromycin and rifampicin compared with clarithromycin alone or no anti-mycobacterial drugs (0% versus 7.1%; OR:0.73). SSTI recurrences were also less common in cases treated with two anti-mycobacterial drugs compared with one or none (10.5% versus 33.3%; OR:0.23).CONCLUSIONS:There was seasonal variation in the incidence of NTM disease, analogous to recently published observations in tuberculosis, which have been linked to seasonal variation in vitamin D. Our finding that anti-mycobacterial combination therapy was associated with a reduced risk of recurrences in patients with NTM lymphadenitis or SSTI requires further confirmation in prospective trials.

Journal of Paediatrics and Child HealthVolume 52, Issue 11 p. 1035-1036 Instructive Case Interesting microorganism Tashunka Taylor-Miller, Corresponding Author Tashunka Taylor-Miller tashunka.taylor-miller@rch.org.au Department of General Medicine, Royal Children's Hospital, Melbourne, Victoria, Australia Correspondence: Dr Tashunka Taylor-Miller, Department of General Medicine, Royal Children's Hospital, 50 Flemington Rd., Parkville, Melbourne, Vic. 3052, Australia. Fax: +61 39345 4751; email: tashunka.taylor-miller@rch.org.auSearch for more papers by this authorMichelle Chapman, Michelle Chapman Department of General Medicine, Royal Children's Hospital, Melbourne, Victoria, AustraliaSearch for more papers by this authorTom Connell, Tom Connell Department of General Medicine, Royal Children's Hospital, Melbourne, Victoria, Australia Murdoch Childrens Research Institute, Melbourne, Victoria, Australia Department of Paediatrics, The University of Melbourne, Melbourne, Victoria, AustraliaSearch for more papers by this authorTheresa Cole, Theresa Cole Department of Allergy and Immunology, Royal Children's Hospital, Melbourne, Victoria, AustraliaSearch for more papers by this authorNigel W Crawford, Nigel W Crawford Department of General Medicine, Royal Children's Hospital, Melbourne, Victoria, Australia Murdoch Childrens Research Institute, Melbourne, Victoria, Australia Department of Paediatrics, The University of Melbourne, Melbourne, Victoria, AustraliaSearch for more papers by this author Tashunka Taylor-Miller, Corresponding Author Tashunka Taylor-Miller tashunka.taylor-miller@rch.org.au Department of General Medicine, Royal Children's Hospital, Melbourne, Victoria, Australia Correspondence: Dr Tashunka Taylor-Miller, Department of General Medicine, Royal Children's Hospital, 50 Flemington Rd., Parkville, Melbourne, Vic. 3052, Australia. Fax: +61 39345 4751; email: tashunka.taylor-miller@rch.org.auSearch for more papers by this authorMichelle Chapman, Michelle Chapman Department of General Medicine, Royal Children's Hospital, Melbourne, Victoria, AustraliaSearch for more papers by this authorTom Connell, Tom Connell Department of General Medicine, Royal Children's Hospital, Melbourne, Victoria, Australia Murdoch Childrens Research Institute, Melbourne, Victoria, Australia Department of Paediatrics, The University of Melbourne, Melbourne, Victoria, AustraliaSearch for more papers by this authorTheresa Cole, Theresa Cole Department of Allergy and Immunology, Royal Children's Hospital, Melbourne, Victoria, AustraliaSearch for more papers by this authorNigel W Crawford, Nigel W Crawford Department of General Medicine, Royal Children's Hospital, Melbourne, Victoria, Australia Murdoch Childrens Research Institute, Melbourne, Victoria, Australia Department of Paediatrics, The University of Melbourne, Melbourne, Victoria, AustraliaSearch for more papers by this author First published: 22 September 2016 https://doi.org/10.1111/jpc.13328 Conflict of interest: None declared. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume52, Issue11November 2016Pages 1035-1036 RelatedInformation