Lower respiratory infections in Australian Indigenous children

Despite Australia being one of the wealthiest countries of the world, Australian Indigenous children have a health status and social circumstance comparable to developing countries. Indigenous infants have 10 times the mortality rate for respiratory conditions. The lower respiratory infection (LRI) rate in Australian Indigenous children is at least as high as that of children in developing countries; the frequency of hospitalisations of Indigenous infants is triple that of non-Indigenous Australian infants (201.7 vs. 62.6/1000, respectively). While Indigenous Australian children have many risk factors for LRIs described in developing countries, there is little specific data, and hence, evidence-based intervention points are yet to be identified. Efficacy of conjugate vaccines for common bacterial causes of pneumonia has been less marked in Indigenous children than that documented overseas. Gaps in the management and prevention of disease are glaring. Given the burden of LRI in Indigenous children and the association with long-term respiratory dysfunction, LRIs should be addressed as a matter of priority.

Increased risk of hospitalization for acute lower respiratory tract infection among Australian Indigenous infants 5-23 months of age following pneumococcal vaccination : a cohort study

Background Australian Indigenous children are the only population worldwide to receive the 7-valent pneumococcal conjugate vaccine (7vPCV) at 2, 4, and 6 months of age and the 23-valent pneumococcal polysaccharide vaccine (23vPPV) at 18 months of age. We evaluated this program's effectiveness in reducing the risk of hospitalization for acute lower respiratory tract infection (ALRI) in Northern Territory (NT) Indigenous children aged 5-23 months. Methods We conducted a retrospective cohort study involving all NT Indigenous children born from 1 April 2000 through 31 October 2004. Person-time at-risk after 0, 1, 2, and 3 doses of 7vPCV and after 0 and 1 dose of 23vPPV and the number of ALRI following each dose were used to calculate dose-specific rates of ALRI for children 5-23 months of age. Rates were compared using Cox proportional hazards models, with the number of doses of each vaccine serving as time-dependent covariates. Results There were 5482 children and 8315 child-years at risk, with 2174 episodes of ALRI requiring hospitalization (overall incidence, 261 episodes per 1000 child-years at risk). Elevated risk of ALRI requiring hospitalization was observed after each dose of the 7vPCV vaccine, compared with that for children who received no doses, and an even greater elevation in risk was observed after each dose of the 23vPPV ( adjusted hazard ratio [HR] vs no dose, 1.39; 95% confidence interval [CI], 1.12-1.71;). Risk was highest among children Pp. 002 vaccinated with the 23vPPV who had received < 3 doses of the 7vPCV (adjusted HR, 1.81; 95% CI, 1.32-2.48). Conclusions Our results suggest an increased risk of ALRI requiring hospitalization after pneumococcal vaccination, particularly after receipt of the 23vPPV booster. The use of the 23vPPV booster should be reevaluated.

Lung health care for Aboriginal and Torres Strait Islander Queenslanders : breathing easy is not so easy

Objectives In Aboriginal and Torres Strait Islander peoples in Queensland, to (a) determine the disease burden of common chronic lung diseases and (b) identify areas of need with respect to lung health services. Methods Literature reviews and analyses of hospitalisation and mortality data were used to describe disease epidemiology and available programs and services. Key stakeholder interviews and an online survey of health professionals were used to evaluate lung health services across the state and to identify services, needs and gaps. Results Morbidity and mortality from respiratory diseases in the Indigenous population is substantially higher than the non-Indigenous population across all age groups and regions. There are inadequate clinical services and resources to address disease prevention, detection, intervention and management in an evidence-based and culturally acceptable fashion. There is a lack of culturally appropriate educational resources and management programs, insufficient access to appropriately engaged Indigenous health professionals, a lack of multi-disciplinary specialist outreach teams, fragmented information systems and inadequate coordination of care. Conclusions Major initiatives are required at all levels of the healthcare system to adequately address service provision for Indigenous Queenslanders with lung diseases, including high quality research to investigate the causes for poor lung health, which are likely to be multifactorial.

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.

Successful application of a simple specimen transport method for the conduct of respiratory virus surveillance in remote Indigenous communities in Australia

Objective Surveillance programs and research for acute respiratory infections in remote Aboriginal communities are complicated by difficulties in the storage and transport of frozen samples to urban laboratories for testing. This study assessed the sensitivity of a simple method for transporting respiratory samples from a remote setting for viral PCR compared with frozen specimens. Methods We sampled every individual who presented to a remote Aboriginal community clinic in a non-epidemic respiratory season. Two anterior nasal swabs were collected from each participant. The left nare specimen was mailed to the laboratory via routine postal services. The right nare specimen was transported frozen. Testing for 16 viruses was undertaken using real-time multiplex PCR. Results A total of 140 participants were enrolled who contributed 150 study visits. Respiratory illnesses accounted for 10% of the reasons for presentation. Sixty-one viruses were identified in 50 (33.3%) presentations for 40 (28.6%) individuals; bocavirus and rhinovirus were the most common viruses identified (14.0% and 12.6% of episodes respectively). The sensitivity for any virus detected in mailed specimens was 67.2% (95%CI 55.4, 78.9) compared to 65.6% (95%CI 53.7, 77.5) for frozen specimens. Conclusion The mailing of unfrozen nasal specimens from remote communities does not compromise the viability of the specimen for viral studies.

Effectiveness of 7-valent pneumococcal conjugate vaccine against radiologically diagnosed pneumonia in indigenous infants in Australia

Objective To evaluate the effectiveness of the 7-valent pneumococcal conjugate vaccine (PCV7) in preventing pneumonia, diagnosed radiologically according to World Health Organization (WHO) criteria, among indigenous infants in the Northern Territory of Australia. Methods We conducted a historical cohort study of consecutive indigenous birth cohorts between 1 April 1998 and 28 February 2005. Children were followed up to 18 months of age. The PCV7 programme commenced on 1 June 2001. All chest X-rays taken within 3 days of any hospitalization were assessed. The primary endpoint was a first episode of WHO-defined pneumonia requiring hospitalization. Cox proportional hazards models were used to compare disease incidence. Findings There were 526 pneumonia events among 10 600 children - an incidence of 3.3 per 1000 child-months; 183 episodes (34.8%) occurred before 5 months of age and 247 (47.0%) by 7 months. Of the children studied, 27% had received 3 doses of vaccine by 7 months of age. Hazard ratios for endpoint pneumonia were 1.01 for 1 versus 0 doses; 1.03 for 2 versus 0 doses; and 0.84 for 3 versus 0 doses. Conclusion There was limited evidence that PCV7 reduced the incidence of radiologically confirmed pneumonia among Northern Territory indigenous infants, although there was a non-significant trend towards an effect after receipt of the third dose. These findings might be explained by lack of timely vaccination and/or occurrence of disease at an early age. Additionally, the relative contribution of vaccine-type pneumococcus to severe pneumonia in a setting where multiple other pathogens are prevalent may differ with respect to other settings where vaccine efficacy has been clearly established.

Towards growing Indigenous culturally competent legal professionals in Australia

The Review of Australian Higher Education (Bradley Review: 2008) identified the need for tertiary institutions to incorporate Indigenous knowledges into curriculum to improve educational outcomes for Indigenous Australians and to increase the cultural competency of all students. It recommended that higher education providers ensure that the institutional culture, the cultural competence of staff and the nature of the curriculum supports the participation of Indigenous students, and that Indigenous knowledge be embedded into curriculum so that all students have an understanding of Indigenous culture. While cultural competency has been recognised as an essential element of professional practice in health services internationally, and legal practice in the United States, very little work has been done to promote the cultural competency of legal professionals in the Australian context. This paper will discuss a pilot cultural competency professional development program for legal academics at Queensland University of Technology (Brisbane) developed with the assistance of a Faculty of Law Teaching and Learning Grant in 2011-2012, and tell one Murri’s journey to foster Indigenous cultural competency in an Australian law school.

Validation of the interRAI Cognitive Performance Scale against independent clinical diagnosis and the Mini-Mental State Examination in older hospitalized patients

Objective To compare the diagnostic accuracy of the interRAI Acute Care (AC) Cognitive Performance Scale (CPS2) and the Mini-Mental State Examination (MMSE), against independent clinical diagnosis for detecting dementia in older hospitalized patients. Design, Setting, and Participants The study was part of a prospective observational cohort study of patients aged ≥70 years admitted to four acute hospitals in Queensland, Australia, between 2008 and 2010. Recruitment was consecutive and patients expected to remain in hospital for ≥48 hours were eligible to participate. Data for 462 patients were available for this study. Measurements Trained research nurses completed comprehensive geriatric assessments and administered the interRAI AC and MMSE to patients. Two physicians independently reviewed patients’ medical records and assessments to establish the diagnosis of dementia. Indicators of diagnostic accuracy included sensitivity, specificity, predictive values, likelihood ratios and areas under receiver (AUC) operating characteristic curves. Results 85 patients (18.4%) were considered to have dementia according to independent clinical diagnosis. The sensitivity of the CPS2 [0.68 (95%CI: 0.58–0.77)] was not statistically different to the MMSE [0.75 (0.64–0.83)] in predicting physician diagnosed dementia. The AUCs for the 2 instruments were also not statistically different: CPS2 AUC = 0.83 (95%CI: 0.78–0.89) and MMSE AUC = 0.87 (95%CI: 0.83–0.91), while the CPS2 demonstrated higher specificity [0.92 95%CI: 0.89–0.95)] than the MMSE [0.82 (0.77–0.85)]. Agreement between the CPS2 and clinical diagnosis was substantial (87.4%; κ=0.61). Conclusion The CPS2 appears to be a reliable screening tool for assessing cognitive impairment in acutely unwell older hospitalized patients. These findings add to the growing body of evidence supporting the utility of the interRAI AC, within which the CPS2 is embedded. The interRAI AC offers the advantage of being able to accurately screen for both dementia and delirium without the need to use additional assessments, thus increasing assessment efficiency.

Promising interventions for reducing Indigenous juvenile offending

Indigenous juveniles (those aged 10 to 16 years in Queensland and 10 to 17 years in all other jurisdictions) are over-represented at all stages of the criminal justice system, and their over-representation becomes more pronounced at the most severe end of the system (ie in detention). Recent figures show that Indigenous juveniles are 24 times as likely to be detained in a juvenile correctional facility as non-Indigenous juveniles (Richards & Lyneham 2010). A variety of explanations for this over-representation have been proposed, including: • lack of access or disparate access to diversionary programs (Allard et al. 2010; Cunneen 2008; Snowball 2008); • systemic discrimination against Indigenous juveniles (eg police bias against Indigenous juveniles) (Cunneen 2008; Kenny & Lennings 2007); • inadequate resourcing of Aboriginal legal services (Cunneen & Schwartz 2008); and • genuinely higher levels of offending by Indigenous juveniles (Kenny & Lennings 2007; Weatherburn et al. 2003). A range of measures (including diversion and juvenile conferencing programs) has recently been implemented to reduce the over-representation of Indigenous juveniles in detention, and minimise the contact of juveniles with the formal criminal justice system. Diversionary measures can only have a limited impact, however, and reducing offending and reoffending have been identified as critical factors to address if the over-representation of Indigenous juveniles is to be reduced (Allard et al. 2010; Weatherburn et al. 2003). While acknowledging that other measures designed to reduce the over-representation of Indigenous juveniles are important, this paper reviews the evidence on policies and programs that reduce offending by Indigenous juveniles in Australia. Where relevant, research from comparable jurisdictions, such as New Zealand and Canada, is also discussed.

Angiogenesis is an independent prognostic factor in malignant mesothelioma

Angiogenesis is essential for tumour growth beyond 1 to 2 mm in diameter. The clinical relevance of angiogenesis, as assessed by microvessel density (MVD), is unclear in malignant mesothelioma (MM). Immunohistochemistry was performed on 104 archival, paraffin-embedded, surgically resected MM samples with an anti-CD34 monoclonal antibody, using the Streptavidin-biotin complex immunoperoxidase technique. 93 cases were suitable for microvessel quantification. MVD was obtained from 3 intratumoural hotspots, using a Chalkley eyepiece graticule at × 250 power. MVD was correlated with survival by Kaplan-Meier and log-rank analysis. A stepwise, multivariate Cox model was used to compare MVD with known prognostic factors and the EORTC and CALGB prognostic scoring systems. Overall median survival from the date of diagnosis was 5.0 months. Increasing MVD was a poor prognostic factor in univariate analysis (P = 0.02). Independent indicators of poor prognosis in multivariate analysis were non-epithelial cell type (P = 0.002), performance status > 0 (P = 0.003) and increasing MVD (P = 0.01). In multivariate Cox analysis, MVD contributed independently to the EORTC (P = 0.006), but not to the CALGB (P = 0.1), prognostic groups. Angiogenesis, as assessed by MVD, is a poor prognostic factor in MM, independent of other clinicopathological variables and the EORTC prognostic scoring system. Further work is required to assess the prognostic importance of angiogenic regulatory factors in this disease. © 2001 Cancer Research Campaign.

Vorinostat/SAHA-induced apoptosis in malignant mesothelioma is FLIP/caspase 8-dependent and HR23B-independent

Introduction: Malignant pleural mesothelioma (MPM) is a rapidly fatal malignancy that is increasing in incidence. The caspase 8 inhibitor FLIP is an anti-apoptotic protein over-expressed in several cancer types including MPM. The histone deacetylase (HDAC) inhibitor Vorinostat (SAHA) is currently being evaluated in relapsed mesothelioma. We examined the roles of FLIP and caspase 8 in regulating SAHA-induced apoptosis in MPM. Methods: The mechanism of SAHA-induced apoptosis was assessed in 7 MPM cell lines and in a multicellular spheroid model. SiRNA and overexpression approaches were used, and cell death was assessed by flow cytometry, Western blotting and clonogenic assays. Results: RNAi-mediated FLIP silencing resulted in caspase 8-dependent apoptosis in MPM cell line models. SAHA potently down-regulated FLIP protein expression in all 7 MPM cell lines and in a multicellular spheroid model of MPM. In 6/7 MPM cell lines, SAHA treatment resulted in significant levels of apoptosis induction. Moreover, this apoptosis was caspase 8-dependent in all six sensitive cell lines. SAHA-induced apoptosis was also inhibited by stable FLIP overexpression. In contrast, down-regulation of HR23B, a candidate predictive biomarker for HDAC inhibitors, significantly inhibited SAHA-induced apoptosis in only 1/6 SAHA-sensitive MPM cell lines. Analysis of MPM patient samples demonstrated significant inter-patient variations in FLIP and caspase 8 expressions. In addition, SAHA enhanced cisplatin-induced apoptosis in a FLIP-dependent manner. Conclusions: These results indicate that FLIP is a major target for SAHA in MPM and identifies FLIP, caspase 8 and associated signalling molecules as candidate biomarkers for SAHA in this disease. © 2011 Elsevier Ltd. All rights reserved.