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.

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.

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.

Mycobacteria-Specific Cytokine Responses Detect Tuberculosis Infection and Distinguish Latent from Active Tuberculosis.

RATIONALE: Current immunodiagnostic tests for tuberculosis (TB), including the tuberculin skin test and IFN-γ release assay (IGRA), have significant limitations, which include their inability to distinguish between latent TB infection (LTBI) and active TB, a distinction critical for clinical management. OBJECTIVES: To identify mycobacteria-specific cytokine biomarkers that characterize TB infection, determine their diagnostic performance characteristics, and establish whether these biomarkers can distinguish between LTBI and active TB. METHODS: A total of 149 children investigated for TB infection were recruited; all participants underwent a tuberculin skin test and QuantiFERON-TB Gold assay. In parallel, whole-blood assays using early secretory antigenic target-6, culture filtrate protein-10, and PPD as stimulatory antigens were undertaken, and cytokine responses were determined by xMAP multiplex assays. MEASUREMENTS AND MAIN RESULTS: IFN-γ, interferon-inducible protein-10 (IP-10), tumor necrosis factor (TNF)-α, IL-1ra, IL-2, IL-13, and MIP-1ß (macrophage inflammatory protein-1ß) responses were significantly higher in LTBI and active TB cases than in TB-uninfected individuals, irrespective of the stimulant. Receiver operating characteristic analyses showed that IP-10, TNF-α, and IL-2 responses achieved high sensitivity and specificity for the distinction between TB-uninfected and TB-infected individuals. TNF-α, IL-1ra, and IL-10 responses had the greatest ability to distinguish between LTBI and active TB cases; the combinations of TNF-α/IL-1ra and TNF-α/IL-10 achieved correct classification of 95.5% and 100% of cases, respectively. CONCLUSIONS: We identified several mycobacteria-specific cytokine biomarkers with the potential to be exploited for immunodiagnosis. Incorporation of these biomarkers into future immunodiagnostic assays for TB could result in substantial gains in sensitivity and allow the distinction between LTBI and active TB based on a blood test alone.

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.

Successful treatment of refractory immune thrombocytopenia with rituximab in a 10-week-old infant.

Immune thrombocytopenic purpura (ITP) that is unresponsive to conventional treatment is uncommon. In this situation, additional therapeutic options are limited and management is challenging. We describe the case of a 10-week-old infant that developed life-threatening ITP that was unresponsive to immunoglobulin and corticosteroids that was successfully managed with the monoclonal antibody rituximab. The literature on the use of rituximab in nonresponsive ITP is reviewed.

The influence of bacille Calmette-Guerin vaccine strain on the immune response against tuberculosis: a randomized trial.

RATIONALE: Approximately 100 million doses of bacille Calmette-Guérin (BCG) vaccine are given each year to protect against tuberculosis (TB). More than 20 genetically distinct BCG vaccine strains are in use worldwide. Previous studies suggest that BCG vaccine strain influences the immune response and protection against TB. Current data on which BCG vaccine strain induces the optimal immune response in humans are insufficient. OBJECTIVES: To compare the immune response to three different BCG vaccine strains given to infants at birth. METHODS: Newborn infants in a tertiary women's hospital were immunized at birth with one of three BCG vaccine strains. A stratified randomization according to the mother's region of birth was used. MEASUREMENTS AND MAIN RESULTS: The presence of mycobacterial-specific polyfunctional CD4 T cells measured by flow cytometry 10 weeks after immunization. Of the 209 infants immunized, data from 164 infants were included in the final analysis (BCG-Denmark, n = 54; BCG-Japan, n = 54; BCG-Russia, n = 57). The proportion of polyfunctional CD4 T cells was significantly higher in infants immunized with BCG-Denmark (0.013%) or BCG-Japan (0.016%) than with BCG-Russia (0.007%) (P = 0.018 and P = 0.003, respectively). Infants immunized with BCG-Japan had higher concentrations of secreted Th1 cytokines; infants immunized with BCG-Denmark had higher proportions of CD107-expressing cytotoxic CD4 T cells. CONCLUSIONS: There are significant differences in the immune response induced by different BCG vaccine strains in newborn infants. Immunization with BCG-Denmark or BCG-Japan induced higher frequencies of mycobacterial-specific polyfunctional and cytotoxic T cells and higher concentrations of Th1 cytokines. These findings have potentially important implications for global antituberculosis immunization policies and future tuberculosis vaccine trials.

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.

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.

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.

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.

Advances in the diagnosis of pulmonary tuberculosis in HIV-infected and HIV-uninfected children.

The identification of improved diagnostic tests for tuberculosis has been identified as a global research priority. Over the past decade, there has been renewed interest in the development and validation of novel diagnostic tools for pulmonary tuberculosis that are applicable to resource-poor settings. These techniques are aimed primarily at improving detection of the organism or a specific host immune response. Although most studies have focused on determining the accuracy of novel tests in adults, it is likely they will also have the capacity to significantly improve the diagnosis of childhood tuberculosis. Improving the quality of clinical samples obtained from children with suspected tuberculosis remains an important research priority while awaiting validation of novel diagnostic tests. This review will focus on a number of recent developments for the diagnosis of tuberculosis, with a specific emphasis on the application of these new tests to children in settings where tuberculosis is endemic.

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.

Reversion and conversion of Mycobacterium tuberculosis IFN-gamma ELISpot results during anti-tuberculous treatment in HIV-infected children.

BACKGROUND: Recent interest has focused on the potential use of serial interferon gamma (IFN-gamma) release assay (IGRA) measurements to assess the response to anti-tuberculous (TB) treatment. The kinetics of IFN-gamma responses to Mycobacterium tuberculosis (MTB) antigens in HIV-infected children during treatment have not however been previously investigated. METHODS: IFN-gamma responses to the MTB antigens, ESAT-6, CFP-10 and PPD were measured by an enzyme-linked immunospot assay (IFN-gamma ELISpot) at presentation and at one, two and six months after starting anti-tuberculous treatment in HIV-infected children with definite or probable TB. Responses at different time points were compared using a Mann-Whitney U test with paired data analysed using the Wilcoxon signed rank test. A Fisher's exact or Chi-squared test was used to compare proportions when test results were analysed as dichotomous outcomes. RESULTS: Of 102 children with suspected TB, 22 (21%) had definite TB and 24 (23%) probable TB. At least one follow up IFN-gamma ELISpot assay result was available for 31 (67%) of the 46 children. In children with definite or probable TB in whom the IFN-gamma ELISpot assay result was positive at presentation, anti-tuberculous treatment was accompanied by a significant decrease in both the magnitude of the IFN-gamma response to individual or combined MTB-specific antigens (ESAT-6 median 110 SFCs/106 PBMC (IQR 65-305) at presentation vs. 15 (10-115) at six months, p = 0.04; CFP-10 177 (48-508) vs. 20 (5-165), p = 0.004, ESAT-6 or CFP-10 median 250 SFCs/106 PBMC (IQR 94-508) vs. 25 (10-165), p = 0.004) and in the proportion of children with a positive IFN-gamma ELISpot assay (Fisher's exact test: ESAT-6 15/0 vs 5/11, p = 0.0002, CFP-10 22/0 vs 8/17, p = 0.0001, ESAT-6 or CFP-10 22/0 vs. 9/17, p= 0.002). However almost half of the children had a positive IFN-gamma ELISpot assay after six months of anti-tuberculous treatment. In addition, there was conversion of the IFN-gamma ELISpot assay result during anti-tuberculous therapy in six of 12 children in whom the initial IFN-gamma ELISpot assay was negative. CONCLUSIONS: In HIV-infected children with definite or probable TB, anti-tuberculosis treatment is accompanied by a reduction in the magnitude of the IFN-gamma ELISpot response to MTB-antigens. However, serial IFN-gamma ELISpot measurements appear to have limited clinical utility in assessing a successful response to anti-tuberculous treatment in HIV infected children.

Perception, attitudes and knowledge regarding the 2009 swine-origin influenza A (H1N1) virus pandemic among health-care workers in Australia.

AIM: To determine the perceptions, attitudes and knowledge of Australian health-care workers (HCWs) regarding the novel, swine-origin influenza A (H1N1) virus (S-OIV) outbreak that reached the country in early May 2009. METHODS: Self-administered, anonymous Web-based survey conducted during the early stages of the S-OIV pandemic. Participants comprised hospital- and community-based medical and nursing staff, medical students, allied health professionals, laboratory staff and administrative personnel. RESULTS: Of the 947 participants surveyed, 59.4% were not convinced that Australia was sufficiently prepared for an influenza pandemic. Only 17.6% of the participants stated they were prepared to work unconditionally during a pandemic; 36.5% stated they would work if they had access to antiviral treatment; 27.9% would if provided with antiviral prophylaxis; and 7.5% would refuse to work. In addition, 37.5% of the participants responded they would refuse or avoid being involved in screening suspected cases. A total of 47.7% admitted to possessing a personal supply of antivirals or having considered this option. Only 48.0% provided a realistic estimate of the mortality associated with an influenza pandemic at a population level. HCWs overestimating the mortality risk and HCWs believing the efficacy of antiviral prophylaxis to be low were significantly less likely to be prepared to work (P= 0.04 and P= 0.0004, respectively). CONCLUSIONS: To ensure adequate staffing during an influenza pandemic, preparedness plans should anticipate significant levels of absenteeism by choice. Interventions aimed at increasing staff retention during a pandemic require further evaluation.

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.

Susceptibility of Mycobacterium bovis BCG vaccine strains to antituberculous antibiotics.

Mycobacterium bovis BCG is one of the most commonly administered vaccines. Complications, including disseminated BCG disease, are rare but increasingly reported in immunodeficient children. There is growing recognition of the importance of differences between BCG vaccine strains. We determined the susceptibilities of five genetically distinct BCG vaccine strains to 12 antituberculous drugs.