Does a 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine prevent respiratory exacerbations in children with recurrent protracted bacterial bronchitis, chronic suppurative lung disease and bronchiectasis : protocol for a randomised controlled trial

Background Recurrent protracted bacterial bronchitis (PBB), chronic suppurative lung disease (CSLD) and bronchiectasis are characterised by a chronic wet cough and are important causes of childhood respiratory morbidity globally. Haemophilus influenzae and Streptococcus pneumoniae are the most commonly associated pathogens. As respiratory exacerbations impair quality of life and may be associated with disease progression, we will determine if the novel 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) reduces exacerbations in these children. Methods A multi-centre, parallel group, double-blind, randomised controlled trial in tertiary paediatric centres from three Australian cities is planned. Two hundred six children aged 18 months to 14 years with recurrent PBB, CSLD or bronchiectasis will be randomised to receive either two doses of PHiD-CV or control meningococcal (ACYW(135)) conjugate vaccine 2 months apart and followed for 12 months after the second vaccine dose. Randomisation will be stratified by site, age (<6 years and >= 6 years) and aetiology (recurrent PBB or CSLD/bronchiectasis). Clinical histories, respiratory status (including spirometry in children aged >= 6 years), nasopharyngeal and saliva swabs, and serum will be collected at baseline and at 2, 3, 8 and 14 months post-enrolment. Local and systemic reactions will be recorded on daily diaries for 7 and 30 days, respectively, following each vaccine dose and serious adverse events monitored throughout the trial. Fortnightly, parental contact will help record respiratory exacerbations. The primary outcome is the incidence of respiratory exacerbations in the 12 months following the second vaccine dose. Secondary outcomes include: nasopharyngeal carriage of H. influenzae and S. pneumoniae vaccine and vaccine-related serotypes; systemic and mucosal immune responses to H. influenzae proteins and S. pneumoniae vaccine and vaccine-related serotypes; impact upon lung function in children aged >= 6 years; and vaccine safety. Discussion As H. influenzae is the most common bacterial pathogen associated with these chronic respiratory diseases in children, a novel pneumococcal conjugate vaccine that also impacts upon H. influenzae and helps prevent respiratory exacerbations would assist clinical management with potential short- and long-term health benefits. Our study will be the first to assess vaccine efficacy targeting H. influenzae in children with recurrent PBB, CSLD and bronchiectasis.

Rates of radiologically confirmed pneumonia as defined by the World Health Organization in Northern Territory Indigenous children

Objective To determine the burden of hospitalised, radiologically confirmed pneumonia (World Health Organization protocol) in Northern Territory Indigenous children. Design, setting and participants Historical, observational study of all hospital admissions for any diagnosis of NT resident Indigenous children, aged between >= 29 days and < 5 years, 1 April 1997 to 31 March 2005. Intervention All chest radiographs taken during these admissions, regardless of diagnosis, were assessed for pneumonia in accordance with the WHO protocol. Main outcome measure The primary outcome was endpoint consolidation (dense fluffy consolidation [alveolar infiltrate] of a portion of a lobe or the entire lung) present on a chest radiograph within 3 days of hospitalisation. Results We analysed data on 24 115 hospitalised episodes of care for 9492 children and 13 683 chest radiographs. The average annual cumulative incidence of endpoint consolidation was 26.6 per 1000 population per year (95% Cl, 25.3-27.9); 57.5 per 1000 per year in infants aged 1-11 months, 38.3 per 1000 per year in those aged 12-23 months, and 13.3 per 1000 per year in those aged 24-59 months. In all age groups, rates of endpoint consolidation in children in the arid southern region of NT were about twice that of children in the tropical northern region. Conclusion The rates of severe pneumonia in hospitalised NT Indigenous children are among the highest reported in the world. Reducing this unacceptable burden of disease should be a national health priority.

Hospitalisation of Indigenous children in the Northern Territory for lower respiratory illness in the first year of life

Objective To describe the epidemiology of acute lower respiratory infection (ALRI) and bronchiectasis in Northern Territory Indigenous infants hospitalised in the first year of life. Design A historical cohort study constructed from the NT Hospital Discharge Dataset and the NT Imm(u)nisation Register. Participants and setting All NT resident Indigenous infants, born 1 January 1999 to 31 December 2004, admitted to NT public hospitals and followed up to 12 months of age. Main outcome measures Incidence of ALRI and bronchiectasis (ICD-10-AM codes) and radiologically confirmed pneumonia (World Health Organization protocol). Results Data on 9295 infants, 8498 child-years of observation and 15 948 hospitalised episodes of care were analysed. ALRI incidence was 426.7 episodes per 1000 child-years (95% Cl, 416.2-437.2). Incidence rates were two times higher (relative risk, 2.12; 95% Cl, 1.98-2.27) for infants in Central Australia compared with those in the Top End. The median age at first admission for an ALRI was 4.6 months (interquartile range, 2.6-7.3). Bronchiolitis accounted for most of the disease burden, with a rate of 227 per 1000 child-years. The incidence of first diagnosis of bronchiectasis was 1.18 per 1000 child-years (95% Cl, 0.60-2.16). One or more key comorbidities were present in 1445 of the 3227 (44.8%) episodes of care for ALRI. Conclusions Rates of ALRI and bronchiectasis in NT Indigenous infants are excessive, with early onset, frequent repeat episodes, and a high prevalence of comorbidities. These high rates of disease demand urgent attention.

Identification of radiological alveolar pneumonia in children with high rates of hospitalized respiratory infections : Comparison of WHO-defined and pediatric pulmonologist diagnosis in the clinical context

Background A reliable standardized diagnosis of pneumonia in children has long been difficult to achieve. Clinical and radiological criteria have been developed by the World Health Organization (WHO), however, their generalizability to different populations is uncertain. We evaluated WHO defined chest radiograph (CXRs) confirmed alveolar pneumonia in the clinical context in Central Australian Aboriginal children, a high risk population, hospitalized with acute lower respiratory illness (ALRI). Methods CXRs in children (aged 1-60 months) hospitalized and treated with intravenous antibiotics for ALRI and enrolled in a randomized controlled trial (RCT) of Vitamin A/Zinc supplementation were matched with data collected during a population-based study of WHO-defined primary endpoint pneumonia (WHO-EPC). These CXRs were reread by a pediatric pulmonologist (PP) and classified as pneumonia-PP when alveolar changes were present. Sensitivities, specificities, positive and negative predictive values (PPV, NPV) for clinical presentations were compared between WHO-EPC and pneumonia-PP. Results Of the 147 episodes of hospitalized ALRI, WHO-EPC was significantly less commonly diagnosed in 40 (27.2%) compared to pneumonia-PP (difference 20.4%, 95% CI 9.6-31.2, P < 0.001). Clinical signs on admission were poor predictors for both pneumonia-PP and WHO-EPC; the sensitivities of clinical signs ranged from a high of 45% for tachypnea to 5% for fever + tachypnea + chest-indrawing. The PPV range was 40-20%, respectively. Higher PPVs were observed against the pediatric pulmonologist's diagnosis compared to WHO-EPC. Conclusions WHO-EPC underestimates alveolar consolidation in a clinical context. Its use in clinical practice or in research designed to inform clinical management in this population should be avoided. Pediatr Pulmonol. 2012; 47:386-392. (C) 2011 Wiley Periodicals, Inc.

Cervical auscultation in the diagnosis of oropharyngeal aspiration in children : a study protocol for a randomised controlled trial

Background Oropharyngeal aspiration (OPA) can lead to recurrent respiratory illnesses and chronic lung disease in children. Current clinical feeding evaluations performed by speech pathologists have poor reliability in detecting OPA when compared to radiological procedures such as the modified barium swallow (MBS). Improved ability to diagnose OPA accurately via clinical evaluation potentially reduces reliance on expensive, less readily available radiological procedures. Our study investigates the utility of adding cervical auscultation (CA), a technique of listening to swallowing sounds, in improving the diagnostic accuracy of a clinical evaluation for the detection of OPA. Methods We plan an open, unblinded, randomised controlled trial at a paediatric tertiary teaching hospital. Two hundred and sixteen children fulfilling the inclusion criteria will be randomised to one of the two clinical assessment techniques for the clinical detection of OPA: (1) clinical feeding evaluation only (CFE) group or (2) clinical feeding evaluation with cervical auscultation (CFE + CA) group. All children will then undergo an MBS to determine radiologically assessed OPA. The primary outcome is the presence or absence of OPA, as determined on MBS using the Penetration-Aspiration Scale. Our main objective is to determine the sensitivity, specificity, negative and positive predictive values of ‘CFE + CA’ versus ‘CFE’ only compared to MBS-identified OPA. Discussion Early detection and appropriate management of OPA is important to prevent chronic pulmonary disease and poor growth in children. As the reliability of CFE to detect OPA is low, a technique that can improve the diagnostic accuracy of the CFE will help minimise consequences to the paediatric respiratory system. Cervical auscultation is a technique that has previously been documented as a clinical adjunct to the CFE; however, no published RCTs addressing the reliability of this technique in children exist. Our study will be the first to establish the utility of CA in assessing and diagnosing OPA risk in young children.

Cough formation in viral infections in children

Using a multidisciplinary approach, Human Respiratory Viral Infections is set at the level between the definitive reference work and an essential clinical manual. Exploring recent advances in human respiratory viral research, the text builds on the basic sciences of epidemiology, virology, molecular biology, and immunology to cover clinical diagnosis, mechanism of pathogenesis, manifestations of disease, impact, treatment, and management strategies.

Citizenship, community, public space and the marginalisation of children and young people

Throughout Australia (and in comparable urban contexts around the world) public spaces may be said to be under attack by developers and also attempts by civic authorities to regulate, restrict, rebrand and reframe them. A consequence of the increasingly security driven, privatised and surveilled nature of public space is the exclusion and displacement of those considered flawed and unwelcome in the ‘spectacular’ consumption spaces of many major urban centres. In the name of urban regeneration, processes of securitisation, ‘gentrification’ and creative cities discourses can refashion public space as sites of selective inclusion and exclusion. In this context of monitoring and control procedures, children and young people’s use of space in parks, neighbourhoods, shopping malls and streets is often viewed as a threat to the social order, requiring various forms of punitive and/or remedial action. This paper discusses developments in the surveillance, governance and control of public space used by children and young people in particular and the capacity for their displacement and marginality, diminishing their sense of place and belonging, and right to public space as an expression of their civil, political and social citizenship(s).

Children's exposure to domestic violence in Australia

Children's 'witnessing' or exposure to domestic violence has been increasingly recognised as a form of child abuse, both in Australia and internationally. Although it is difficult to accurately assess the scope of the problem, research has demonstrated that a substantial amount of domestic violence is witnessed by children. As this paper outlines, witnessing domestic violence can involve a range of incidents, ranging from the child 'only' hearing the violence, to the child being forced to participate in the violence or being used as part of a violent incident. In this paper, current knowledge about the extent of children's exposure to domestic violence in Australia is described, along with the documented impacts that this exposure can have on children. This includes psychological and behavioural impacts, health and socioeconomic impacts, and its link to the intergenerational transmission of violence and re-victimisation. Current legislative and policy initiatives are then described and some community-based programs that have been introduced in Australia to address the problem of children's exposure to domestic violence are highlighted. The paper concludes that initiatives focused on early intervention and holistic approaches to preventing and responding to children's exposure to domestic violence should be considered as part of strategies developed to address this problem.

Understanding theory of mind in children who are deaf

Research on theory of mind began in the context of determining whether chimpanzees are aware that individuals experience cognitive and emotional states. More recently, this research has involved various groups of children and various tasks, including the false belief task. Based almost exclusively on that paradigm, investigators have concluded that although ``normal'' hearing children develop theory of mind by age 5, children who are autistic or deaf do not do so until much later, perhaps not until their teenage years. The present study explored theory of mind by examining stories told by children who are deaf and hearing (age 9±15 years) for statements ascribing behaviour-relevant states of mind to themselves and others. Both groups produced such attributions, although there were reliable differences between them. Results are discussed in terms of the cognitive abilities assumed to underlie false belief and narrative paradigms and the implications of attributing theory of mind solely on the basis of performance on the false belief task.

Shrinkage empirical likelihood estimator in longitudinal analysis with time-dependent covariates-application to modeling the health of Filipino children

The method of generalized estimating equations (GEE) is a popular tool for analysing longitudinal (panel) data. Often, the covariates collected are time-dependent in nature, for example, age, relapse status, monthly income. When using GEE to analyse longitudinal data with time-dependent covariates, crucial assumptions about the covariates are necessary for valid inferences to be drawn. When those assumptions do not hold or cannot be verified, Pepe and Anderson (1994, Communications in Statistics, Simulations and Computation 23, 939–951) advocated using an independence working correlation assumption in the GEE model as a robust approach. However, using GEE with the independence correlation assumption may lead to significant efficiency loss (Fitzmaurice, 1995, Biometrics 51, 309–317). In this article, we propose a method that extracts additional information from the estimating equations that are excluded by the independence assumption. The method always includes the estimating equations under the independence assumption and the contribution from the remaining estimating equations is weighted according to the likelihood of each equation being a consistent estimating equation and the information it carries. We apply the method to a longitudinal study of the health of a group of Filipino children.