Comprehensive care programmes for children with medical complexity.

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.

Prevalence of Nonalcoholic Steatohepatitis and Associated Fibrosis Stages Among US Adults Using Imaging-Based vs Biomarker-Based Noninvasive Tests.

Introduction: Nonalcoholic fatty liver disease (NAFLD) is believed to be the most common chronic liver disease worldwide. Therapies are under development for nonalcoholic steatohepatitis (NASH), the progressive form of NAFLD, such that the prevalence of NASH with liver fibrosis, which is likely to require treatment, may be of interest to healthcare decision makers. Noninvasive tests are used in initial screening for NASH, as well as in observational studies of NASH prevalence. However, existing evidence does not address how estimated prevalence varies with different noninvasive tests. This analysis estimated the prevalence of NASH among US adults and assessed variation with different noninvasive tests. Methods: A cross-sectional analysis was conducted using the 2017-March 2020 National Health and Nutrition Examination Survey cycle. Participants with presumed NAFLD (steatosis and without alternative causes of liver disease) were identified, among whom NASH was predicted based on FAST score, Fibrosis-4 (FIB-4), and AST-to-Platelet Ratio Index (APRI) cutoffs across 11 scenarios. Among NASH participants, fibrosis stages were explored based on distribution across the spectrum of liver-stiffness measurements. Results: Among participants with complete data for the analysis (N=6969), prevalence of presumed NAFLD was 25.6%. Within presumed NAFLD, prediction of NASH using imaging-based NIT cutoffs yielded estimated prevalence of 1.3%-4.8% (3.3 million-12.2 million) based on FAST score cutoffs from 0.35-0.67. Using biomarker-based NIT cutoffs yielded estimated prevalence of 0.4%-12.3% (1.0 million-14.5 million) based on FIB-4 cutoffs from 0.90-2.67, and 0.1%-1.9% (0.2-5.0 million) based on APRI cutoffs from 0.50-1.50. Conclusion: Prevalence of NASH among US adults was estimated to range from 1.3% to 4.8% when predicted using imaging-based noninvasive test values for participants with presumed NAFLD, generally aligning with estimates in the literature of prevalence of biopsy-confirmed NASH. Use of biomarker-based noninvasive test values for prediction of NASH yielded a wider range of estimates with FIB-4, and a considerably lower range of estimates with APRI.

Inborn Errors of Immunity in Children With Invasive Pneumococcal Disease: A Multicenter Prospective Study.

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.

Matching-Adjusted Indirect Comparison Between Risankizumab and Ustekinumab for Induction and Maintenance Treatment of Moderately to Severely Active Crohn's Disease.

INTRODUCTION: Risankizumab (RZB) and ustekinumab (UST), interleukin (IL)-23 and IL-12/23 inhibitors, respectively, are approved treatments for moderately to severely active Crohn's disease (CD); direct comparison between the two is ongoing. We indirectly compared efficacy of RZB versus UST using data from phase 3 trials (RZB: NCT03104413; NCT03105128; NCT03105102; UST: NCT01369329; NCT01369342; NCT01369355). METHODS: Matching-adjusted indirect comparison was conducted using individual patient-level data from RZB trials and published aggregated data from UST trials. During induction, patients received RZB 600 mg intravenous (IV) at weeks 0, 4, and 8 or a single dose of UST 6 mg/kg IV at week 0. During maintenance, patients received RZB 180 or 360 mg subcutaneous (SC) or UST 90 mg SC every 8 or 12 weeks to 52 weeks. Outcomes included proportion of patients achieving Crohn's Disease Activity Index (CDAI) response (decrease of ≥ 100 points or total score < 150) or remission (CDAI ≤ 150) and endoscopic improvement (measured by the Simple Endoscopic Score in CD [SES-CD]; response, ≥ 50% reduction from baseline; remission, SES-CD ≤ 2) following induction/baseline. RESULTS: Higher proportions of patients achieved clinical and endoscopic outcomes with RZB vs. UST induction treatment, resulting in significantly (p ≤ 0.05) greater percent differences (95% confidence intervals) between groups for CDAI remission (15% [5%, 25%]) and endoscopic response (26% [13%, 40%]) and remission (9% [0%, 19%]). Following maintenance, rates of CDAI remission were similar (range - 0.3% to - 5.0%) for RZB vs. UST. Differences for endoscopic response and remission ranged from 9.3% to 27.7% and 11.6% to 12.5%, respectively; differences were significant (p < 0.05) for endoscopic response for both doses of RZB compared to UST 12-week dosing. CONCLUSIONS: This indirect comparison demonstrated higher rates of clinical and endoscopic outcomes during induction for RZB compared to UST; CDAI remission following maintenance was comparable. Direct comparisons of RZB and UST are warranted to validate these findings.

Using individual patient-level data from risankizumab and aggregated data from ustekinumab phase 3 Crohn's disease trials, we indirectly compared efficacy of risankizumab and ustekinumab to determine whether rates of improvement in disease symptoms (clinical) and endoscopic outcomes differed between treatments. Findings showed that clinical and endoscopic outcomes were more frequently achieved for patients receiving risankizumab versus ustekinumab after induction, while most maintenance outcomes were comparable.

Health of children who experienced Australian immigration detention.

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.

Observational Analysis of the Costs Associated with Acute Treatment of Breakthrough Migraine Attacks in Medicaid Patients Using Preventive Therapies.

INTRODUCTION: Medications for preventive treatment of migraine reduce migraine frequency, usually measured by a reduction in monthly migraine days (MMD), but generally do not eliminate the need for acute treatment. To assess the economic impact of treatment-related reductions in frequency, methodological guidance recommends capturing cost differences along the spectrum of MMD. OBJECTIVE: Characterize monthly migraine medication costs along the spectrum of MMD for patients using calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) for prevention. METHODS: Medicaid State Drug Utilization Data (SDUD) were used to identify formulations and per-unit costs for oral, intranasal, and parenteral migraine-specific medications for acute and preventive treatment used by fee-for-service (FFS) Medicaid enrollees in 2020. National drug codes of relevant therapies were used to match SDUD to formulation characteristics including substance, route of administration, and branded/generic marketing status. Mean per-unit cost and the formulation's share of total prescriptions were estimated. Monthly medication costs were modeled based on formulations' per-unit costs and frequency of acute medication use during clinical trials of CGRP mAbs. RESULTS: In the SDUD, there were 563,338 prescriptions for migraine-specific acute medications; triptans accounted for 97.37%. Triptan formulations prescribed were 83.78% oral tablet, 10.89% orally disintegrating tablet, 2.60% intranasal, and 2.73% parenteral. Dihydroergotamine accounted for < 1% of total prescriptions and had the highest per-unit cost ($443.50, branded intranasal). There were 97,119 prescriptions for CGRP mAbs, the majority for erenumab (45.73%) or galcanezumab (45.24%). Modeled monthly acute and preventive medication costs ranged from approximately $550 in patients with the fewest MMD treated with oral triptans to > $1500 in patients with the most MMD treated with dihydroergotamine. CONCLUSION: In consideration of the migraine-specific acute medications used in FFS Medicaid 2020, for patients using CGRP mAbs for prevention, medication costs may vary significantly with the number of breakthrough attacks treated per month and the type of migraine-specific acute therapy used.

Not just a chalazion-focal eyelid and orbital infection with Saksaenea vasiformis in an immunocompetent child.

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.

Follow-up and Clinical Outcomes of Human Immunodeficiency Virus (HIV)-Exposed Infants in A Low-Prevalence Setting in A Multidisciplinary Model of Care in Australia: The Children's HIV Exposure Study 1.

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.

Structuring ward rounds to enhance education.

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.

Mycobacteria-Specific Mono- and Polyfunctional CD4+ T Cell Profiles in Children With Latent and Active Tuberculosis: A Prospective Proof-of-Concept Study.

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.

Pulmonary Mycobacterium abscessus complex in children with cystic fibrosis: A practical management guideline.

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.

Treatment and secondary prophylaxis with ethanol lock therapy for central line-associated bloodstream infection in paediatric cancer: a randomised, double-blind, controlled trial.

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. FUNDING: American Lebanese Syrian Associated Charities to St Jude Children's Research Hospital and an Australian Government Research Training Scholarship.

Splenic cyst and its management in a 21-month-old boy: a rare complication of invasive meningococcal disease.

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.

Evaluating an admission avoidance pathway for children in the emergency department: outpatient intravenous antibiotics for moderate/severe cellulitis.

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.

A Comparison of Hospital Versus Outpatient Parenteral Antibiotic Therapy at Home for Pyelonephritis and Meningitis.

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.

Comparable CD4 and CD8 T cell responses and cytokine release after at-birth and delayed BCG immunisation in infants born in Australia.

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.

Nontuberculous Mycobacterial Disease in Children - Epidemiology, Diagnosis & Management at a Tertiary Center.

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.

Congenital Tuberculosis Complicated by Hemophagocytic Lymphohistiocytosis.

We present the case of a male infant with congenital tuberculosis in a nonendemic setting complicated by hemophagocytic lymphohistiocytosis, who was treated successfully with antituberculous therapy and corticosteroids. We review the pediatric literature concerning the unusual association of these 2 rare conditions.