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Fractional exhaled nitric oxide (Feno), used as a biomarker, is influenced by several factors including ethnicity. Normative data are essential for interpretation, and currently single cutoff values are used in children and adults.Accounting for factors that influence Feno, (1) what are appropriate predicted and upper limit of normal (ULN) Feno values in an underserved population (First Nations Australians), (2) how do these values compare with age-based interpretive guidelines, and (3) what factors influence Feno and what is the size of the effect?Feno data of First Nations Australians (age 16 years, n = 862; age ≥ 16 years, n = 348) were obtained. Medical history using participant questionnaires and medical records were used to define healthy participants. Flexible regression using spline functions, as used by the Global Lung Function Initiative, were used to generate predicted and ULN values.Look-up tables for predicted and ULN values using age (4-76 years) and height (100-200 cm) were generated and are supplied with a calculator for clinician use. In healthy First Nations children (age 18 years), ULN values ranged between 25 and 60 parts per billion (ppb) when considering only biologically plausible age and height combinations. For healthy adults, ULN values ranged between 39 and 88 ppb. Neither the current Feno interpretation guidelines, nor the currently recommended cutoff of 50 ppb for First Nations children 16 years of age or younger were appropriate for use in this cohort. Our modelling revealed that predicted and ULN values of healthy participants varied nonlinearly with age and height.Because single pediatric, adult, or all-age Feno cutoff values used by current interpretive guidelines to define abnormality fail to account for factors that modify Feno values, we propose predicted and ULN values for First Nations Australians 4 to 76 years of age. Creating age- and height-adjusted predicted and ULN values could be considered for other ethnicities.

Australian First Nations children are at very high risk of early, recurrent, and persistent bacterial otitis media and respiratory tract infection. With the PREVIX randomised controlled trials, we aimed to evaluate the immunogenicity of novel pneumococcal conjugate vaccine (PCV) schedules.PREVIX_BOOST was a parallel, open-label, outcome-assessor-blinded, randomised controlled trial. Aboriginal children living in remote communities of the Northern Territory of Australia were eligible if they had previously completed the three-arm PREVIX_COMBO randomised controlled trial of the following vaccine schedules: three doses of a 13-valent PCV (PCV13; PPP) or a ten-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10; SSS) given at 2, 4, and 6 months, or SSS given at 1, 2, and 4 months followed by PCV13 at 6 months (SSSP). At age 12 months, eligible children were randomly assigned by a computer-generated random sequence (1:1, stratified by primary group allocation) to receive either a PCV13 booster or a PHiD-CV10 booster. Analyses used intention-to-treat principles. Co-primary outcomes were immunogenicity against protein D and serotypes 3, 6A, and 19A. Immunogenicity measures were geometric mean concentrations (GMC) and proportion of children with IgG concentrations of 0·35 μg/mL or higher (threshold for invasive pneumococcal disease), and GMCs and proportion of children with antibody levels of 100 EU/mL or higher against protein D. Standardised assessments of otitis media, hearing impairment, nasopharyngeal carriage, and developmental outcomes are reported. These trials are registered with ClinicalTrials.gov (NCT01735084 and NCT01174849).Between April 10, 2013, and Sept 4, 2018, 261 children were randomly allocated to receive a PCV13 booster (n=131) or PHiD-CV10 booster (n=130). Adequate serum samples for pneumococcal serology were obtained from 127 (95%) children in the PCV13 booster group and 126 (97%) in the PHiD-CV10 booster group; for protein D, adequate samples were obtained from 126 (96%) children in the PCV13 booster group and 123 (95%) in the PHiD-CV10 booster group. The proportions of children with IgG concentrations above standard thresholds in PCV13 booster versus PHiD-CV10 booster groups were the following: 71 (56%) of 126 versus 81 (66%) of 123 against protein D (difference 10%, 95% CI -2 to 22), 85 (67%) of 127 versus 59 (47%) of 126 against serotype 3 (-20%, -32 to -8), 119 (94%) of 127 versus 91 (72%) of 126 against serotype 6A (-22%, -31 to -13), and 116 (91%) of 127 versus 108 (86%) of 126 against serotype 19A (-5%, -13 to 3). Infant PCV13 priming mitigated differences between PCV13 and PHiD-CV10 boosters. In both groups, we observed a high prevalence of otitis media (about 90%), hearing impairment (about 75%), nasopharyngeal carriage of pneumococcus (about 66%), and non-typeable H influenzae (about 57%). Of 66 serious adverse events, none were vaccine related.Low antibody concentrations 6 months post-booster might indicate increased risk of pneumococcal infection. The preferred booster was PCV13 if priming did not have PCV13, otherwise either PCV13 or PHiD-CV10 boosters provided similar immunogenicity. Mixed schedules offer flexibility to regional priorities. Non-PCV13 serotypes and non-typeable H influenzae continue to cause substantial disease and disability in Australian First Nation's children.National Health and Medical Research Council (NHMRC).

Objectives: Understand the long-term mortality, risk of readmission for sepsis and cause of death following a gram-negative bloodstream infection (GN-BSI). Methods: This was a propensity-matched study using data linkage of Queensland hospital data, Australia. GN-BSIs were collected from 2005 to 2010 and matched 1:1 to hospital admissions without BSI for age, gender, year of culture collection, frequency of admissions in the prior year and Charlson-Deyo Comorbidity score and each comorbidity within the Charlson-Deyo score. Readmissions for sepsis, mortality and causes of death were evaluated. Results: Cases of GN-BSI were propensity-matched 1:1 to culture-negative hospital admissions (n = 14016). Readmissions for sepsis were higher in the GN-BSI cohort from 91 to 365 days (P

Antecedents of the high rates of chronic kidney disease in Australian Indigenous peoples may originate early in life. Fourteen percent of Australian Indigenous infants are born preterm (under 37 weeks gestation) and, therefore, at risk. Here, our observational cohort study sought to determine the impact of preterm birth on renal function in Australian Indigenous and non-Indigenous infants. Renal function was assessed between 4-29 days postnatally in 60 Indigenous and 42 non-Indigenous infants born at 24-36 weeks gestation. Indigenous ethnicity was associated with impaired renal function, with significantly higher serum creatinine (geometric mean ratio (GMR) 1.15 [1.06, 1.25]), fractional excretion of sodium (GMR 1.21 [1.04, 1.39]), and urine albumin (GMR 1.57 [1.05, 2.34]), β-2 microglobulin (GMR 1.82 [1.11, 2.98]) and cystatin C (GMR 3.27 [1.54, 6.95]) when controlling for gestational/postnatal age, sex and birth weight Z-score. Renal injury, as indicated by high urine neutrophil gelatinase-associated lipocalin levels, was associated with maternal smoking and postnatal antibiotic exposure. Indigenous infants appeared to be most susceptible to the adverse impact of antibiotics. These findings show that preterm Australian Indigenous infants are highly vulnerable to renal dysfunction. Preterm birth may contribute to their increased risk of chronic kidney disease. Thus, we recommended that renal function should be closely monitored life-long in Indigenous children born preterm.

Summary Background Bronchiectasis guidelines recommend antibiotics for the treatment of acute respiratory exacerbations, but randomised placebo-controlled trials in children are lacking. We hypothesised that oral amoxicillin–clavulanate and azithromycin would each be superior to placebo in achieving symptom resolution of non-severe exacerbations in children by day 14 of treatment. Methods In this multicentre, three-arm, parallel, double-dummy, double-blind, randomised placebo-controlled trial at four paediatric centres in Australia and New Zealand, we enrolled children aged 1–18 years with CT-confirmed bronchiectasis unrelated to cystic fibrosis, who were under the care of a respiratory physician and who had had at least two respiratory exacerbations in the 18 months before study entry. Participants were allocated (1:1:1) at exacerbation onset to receive oral suspensions of amoxicillin–clavulanate (45 mg/kg per day) plus placebo azithromycin, azithromycin (5 mg/kg per day) plus placebo amoxicillin–clavulanate, or both placebos for 14 days. An independent statistician prepared a computer-generated, permuted-block (size 2–8) randomisation sequence, stratified by centre, age, and cause. Participants, caregivers, study coordinators, and investigators were masked to treatment assignment until data analysis was completed. The primary outcome was the proportion of children with exacerbation resolution by day 14 in the intention-to-treat population. Treatment groups were compared using generalised linear models. Statistical significance was set at p

Background Fractional exhaled nitric oxide (Feno) is used clinically as a biomarker of eosinophilic airway inflammation. Awareness of the factors influencing Feno values is important for valid clinical interpretation. Methods We undertook a systematic review of PubMed, Cochrane Library, Scopus, and Web of Science databases and reference lists of included articles to evaluate whether ethnicity influences Feno values, and to determine if this influence affects clinical interpretation according to current guidelines. We included all studies that performed online Feno measurements on at least 25 healthy, non-Caucasian individuals, and examined the effect of ethnicity on Feno. Results From 62 potential studies, 12 studies were included. One study recruited only children ( Conclusions Ethnicity influences Feno values, and for some ethnic groups this influence likely affects clinical interpretation according to current guidelines. There is a need to establish healthy Feno reference ranges for specific ethnic groups to improve clinical application.

Summary Background Evidence is mounting that price discounts can be effective in improving diet. This study examined the effectiveness of a 20% price discount on food and drink purchases with and without consumer education in remote Indigenous Australia. Methods A 20% discount on fruit, vegetables, water, and artificially sweetened soft drinks was applied for 24 weeks in 20 communities in remote Indigenous Australia where the community store was managed by the Arnhem Land Progress Aboriginal Corporation (ALPA) or Outback Stores (OBS) in a stepped-wedge randomised trial. Communities were randomly allocated to a fixed framework of five sets of four stratified by store association; ten stores (two in each set) were randomly assigned to receive consumer education. A store from each of the ALPA and OBS store groups (contained in separate opaque envelopes) was selected, and stores in turn continued to be consecutively allocated to the fixed store set framework, starting with the first store slot in the first store set, until all stores had been allocated. The effect of the discount on the weight of fruit and vegetables purchased (the primary endpoint) was assessed using weekly store sales data and mixed models per protocol. We did sensitivity analyses by repeating the analyses with the outliers included and repeating the analyses for the primary outcome measure removing each store one at a time. This trial was registered with Australian New Zealand Clinical Trials Registry, number ACTRN12613000694718. Findings Weekly store sales data on all food and drink products sold in 20 stores were collected from July 1, 2012, to Dec 28, 2014. Price discount alone was associated with a 12·7% (95% CI 4·1–22·1) increase in purchases in grams of fruit and vegetables combined (primary outcome), and a 19·8% (6·2–35·1) increase post discount (after vs before); an effect of 12 g and 18 g per capita per day. Sensitivity analyses did not modify the results for the primary outcome measure. Interpretation A 20% discount can only increase fruit and vegetable purchases to help protect against obesity and diet related disease to a certain extent. Large discounts might have a greater impact than small discounts. Creative merchandising approaches to consumer education could also be considered alongside fiscal interventions to achieve marked improvements in diet. Funding Australian National Health and Medical Research Council.

Background: Bronchiectasis guidelines recommend antibiotics for treating acute respiratory exacerbations, but placebo-controlled, randomised-controlled trials (RCTs) are lacking in children. Since many exacerbations are virus-triggered, antibiotics may be unnecessary for non-severe (non-hospitalised) episodes. We hypothesised that oral amoxicillin-clavulanate and azithromycin are both superior to placebo for achieving symptom resolution by day-14 when treating non-severe exacerbations in children. Methods: In this multicentre (n=4), parallel, double-dummy, double-blind, placebo-controlled three-arm RCT, children aged 1-19 years were randomised at exacerbation onset to receive: (a) amoxicillin-clavulanate (45mg/kg/day)/azithromycin-placebo, (b) azithromycin (5mg/kg/day)/amoxicillin-clavulanate-placebo, or (c) placebo/placebo for 14-days (Australian-New Zealand Registry, ACTRN12612000011886). The primary outcome was exacerbation resolution by day-14. Secondary outcomes included exacerbation duration, time-to-next exacerbation, parent cough-specific quality-of-life, laboratory and spirometry assessments and nasopharyngeal microbiology. Treatment arms were compared using generalised-linear-models. Statistical significance was set at p

We aimed to examine the prognostic values of established risk factors and to validate the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in an independent series of patients with malignant pleural mesothelioma (MPM).A total of 148 patients who applied for compensation at the Dust Diseases Board from 2007 to 2009 were included in this study. Overall survival was determined by the Kaplan-Meier method, and NLR was defined as the absolute neutrophil divided by the lymphocyte count. The prognostic value of the variables was examined by using Cox regression analysis, and all factors were entered into a multivariate model to determine their independent effect.The patient characteristics were median age of 73 years; 93% men; 59% epithelial subtype; median NLR of 3.5 at diagnosis (n = 79); median overall survival of 10.6 months. The following variables were predictive of longer overall survival in univariate analysis: younger age, epithelial subtype, lower tumor stage, low white cell count, low platelet count, low hemoglobin level, and low NLR. Multivariate analysis confirmed that nonepithelial vs. epithelial subtype (hazard ratio [HR], 3.0; P.001), tumor stage (HR, 1.6; P.001), hemoglobin level difference ≥10 vs.10 (HR, 2.0; P = .03), no chemotherapy vs. use of chemotherapy (HR, 2.4; P.001), and NLR ≥3 vs.3 (HR, 2.2; P.01) were independently associated with prognosis.Apart from previously recognized factors, such as histosubtype, tumor stage, and hemoglobin level difference, NLR, an index of systemic inflammation bears prognostic significance that shows that a snapshot of immune status is able to convey important prognostic information.

Background: Insulin sensitivity (Si) is improved by weight loss and exercise, but the effects of the replacement of saturated fatty acids (SFAs) with monounsaturated fatty acids (MUFAs) or carbohydrates of high glycemic index (HGI) or low glycemic index (LGI) are uncertain.Objective: We conducted a dietary intervention trial to study these effects in participants at risk of developing metabolic syndrome.Design: We conducted a 5-center, parallel design, randomized controlled trial [RISCK (Reading, Imperial, Surrey, Cambridge, and Kings)]. The primary and secondary outcomes were changes in Si (measured by using an intravenous glucose tolerance test) and cardiovascular risk factors. Measurements were made after 4 wk of a high-SFA and HGI (HS/HGI) diet and after a 24-wk intervention with HS/HGI (reference), high-MUFA and HGI (HM/HGI), HM and LGI (HM/LGI), low-fat and HGI (LF/HGI), and LF and LGI (LF/LGI) diets.Results: We analyzed data for 548 of 720 participants who were randomly assigned to treatment. The median Si was 2.7 x 10(-4) mL . mu U-1 . min(-1) (interquartile range: 2.0, 4.2 x 10(-4) mL . mu U-1 . min(-1)), and unadjusted mean percentage changes (95% CIs) after 24 wk treatment (P = 0.13) were as follows: for the HS/HGI group, -4% (-12.7%, 5.3%); for the HM/HGI group, 2.1% (-5.8%, 10.7%); for the HM/LGI group, -3.5% (-10.6%, 4.3%); for the LF/HGI group, -8.6% (-15.4%, -1.1%); and for the LF/LGI group, 9.9% (2.4%, 18.0%). Total cholesterol (TC), LDL cholesterol, and apolipoprotein B concentrations decreased with SFA reduction. Decreases in TC and LDL-cholesterol concentrations were greater with LGI. Fat reduction lowered HDL cholesterol and apolipoprotein A1 and B concentrations.Conclusions: This study did not support the hypothesis that iso-energetic replacement of SFAs with MUFAs or carbohydrates has a favorable effect on Si. Lowering GI enhanced reductions in TC and LDL-cholesterol concentrations in subjects, with tentative evidence of improvements in Si in the LF-treatment group. This trial was registered at clinicaltrials.gov as ISRCTN29111298. Am J Clin Nutr 2010;92:748-58.

Our objective in this study was to develop and implement an effective intervention strategy to manipulate the amount and composition of dietary fat and carbohydrate (CHO) in free-living individuals in the RISCK study. The study was a randomized, controlled dietary intervention study that was conducted in 720 participants identified as higher risk for or with metabolic syndrome. All followed a 4-wk run-in reference diet [high saturated fatty acids (SF)/high glycemic index (GI)]. Volunteers were randomized to continue this diet for a further 24 wk or to 1 of 4 isoenergetic prescriptions [high monounsaturated fatty acids (MUFA)/high GI; high MUFA/low GI; low fat (LF)/high GI; and LF/low GI]. We developed a food exchange model to implement each diet. Dietary records and plasma phospholipid fatty acids were used to assess the effectiveness of the intervention strategy. Reported fat intake from the LF diets was significantly reduced to 28% of energy (%E) compared with 38%E from the HM and LF diets. SF intake was successfully decreased in the HM and LF diets to < or =10%E compared with 17%E in the reference diet (P = 0.001). Dietary MUFA in the HM diets was approximately 17%E, significantly higher than in the reference (12%E) and LF diets (10%E) (P = 0.001). Changes in plasma phospholipid fatty acids provided further evidence for the successful manipulation of fat intake. The GI of the HGI and LGI arms differed by approximately 9 points (P = 0.001). The food exchange model provided an effective dietary strategy for the design and implementation across multiple sites of 5 experimental diets with specific targets for the proportion of fat and CHO.

Objectives Longitudinal studies of the elderly are complicated by the loss of individuals between waves due to death or other dropout mechanisms. Factors that affect dropout may well be similar from one study to another. This article systematically reviews all large population-based studies of the elderly (published 1966–2002) that report on differences in individual characteristics between people who remain and people who dropout at follow-up. Study design and setting A systematic review of articles that investigate attrition after baseline interview. Results Twelve studies were found that investigated dropout other than death using unadjusted, multivariable methods or both. The unadjusted analyses showed many significant factors related to attrition. Multivariable analyses showed two main independent factors were related to increased attrition: increasing age and cognitive impairment. People who were very ill or frail had higher dropout rates, and people in worse health were less likely to be recontactable. Conclusions Multivariable methods of analyzing attrition in longitudinal studies show consistent patterns of dropout between differing studies, with a small number of key relationships. These findings will assist researchers when planning studies of older people, and provide insight into the possible biases in longitudinal studies introduced by differential dropout.

F04-9-33 A single dose of azithromcyin has no clinical efficacy in children aged ≤18 months hospitalised with acute bronchiolitis: a double-blinded, randomized, placebo-controlled trial G.B. McCallum, P.S. Morris, M. Chatfield, C. MacLennan, A. White, L. Versteegh, C. Wilson, S. Pizzutto, N. Jacobsen, A. Chang. Menzies School of Health Research Respiratory group – Child Health Division, Darwin, Australia; University of Sydney NHMRC Clinical Trial Centre, Sydney, Australia; Royal Darwin Hospital Department of Paediatrics, Darwin, Australia; The Townsville Hospital Department of Paediatrics, Townsville, Australia; Royal Children’s Hospital Deparment of Respiartory Medicine, Brisbane, Australia