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Objectives: Gestational age at birth is declining, probably because more deliveries are being induced. Gestational age is an important modifiable risk factor for neonatal mortality and morbidity. We aimed to investigate the association between gestational age and mortality in hospital for term-born neonates (>= 37 wk') admitted to PICUs in Australia and New Zealand. Design: Observational multicenter cohort study. Setting: PICUs in Australia and New Zealand. Patients: Term-born neonates (>= 37 wk) admitted to PICUs. Interventions: None Measurements and Main Results: We studied 5,073 infants born with a gestational age greater than or equal to 37 weeks and were less than 28 days old when admitted to a PICU in Australia or New Zealand between 2007 and 2016. The association between gestational age and mortality was estimated using a multivariable logistic regression model, adjusting for age, sex, indigenous status, Pediatric Index of Mortality version 2, and site. The median gestational age was 39.1 weeks (interquartile range, 38.2-40 wk) and mortality in hospital was 6.6%. Risk of mortality declined log-linearly with gestational age. The adjusted analysis showed a 20% (95% CI, 11-28%) relative reduction in mortality for each extra week of gestation beyond 37 weeks. The effect of gestation was stronger among those who received extracorporeal life support: each extra week of gestation was associated with a 44% (95% CI, 25-57%) relative reduction in mortality. Longer gestation was also associated with reduced length of stay in hospital: each week increase in gestation, the average length of stay decreased by 4% (95% CI, 2-6%). Conclusions: Among neonates born at "term" who are admitted to a PICU, increasing gestational age at birth is associated with a substantial reduction in the risk of dying in hospital. The maturational influence on outcome was more strongly noted in the sickest neonates, such as those requiring extracorporeal life support. This information is important in view of the increasing proportion of planned births in both high- and low-/middle-income countries.

Objectives To investigate if the performance of Pediatric Index of Mortality 3 is improved by including imputed values for the PaO2/FIO2 ratio where measurements of PaO2 or FIO2 are missing. Design A prospective observational study. Setting A bi-national pediatric intensive care registry. Patients The records of 37,983 admissions of children less than 16 years old admitted to 19 ICUs. Interventions None. Measurements and main results Seven published equations describing an association between PaO2/FIO2 and oxygen saturation measured by pulse oximetry (SpO2)/FIO2 were used to derive an alternative variable d100 × FIO2/PaO2 for the Pediatric Index of Mortality 3 variable 100 × FIO2/PaO2. Six equations exclude SpO2/FIO2 values if SpO2 is greater than 96-98%. 100 × FIO2/PaO2 was missing in 72% of patient records primarily due to missing PaO2, d100 × FIO2/PaO2 was missing in 71% of patient records if values of SpO2greater than 97% were excluded or in 17% of patient records if all measurements of SpO2 were included. Univariable analysis supported the inclusion of SpO2 values greater than 97%. Compared to the standard Pediatric Index of Mortality 3 model, two alternative models imputing 100 × FIO2/PaO2 from d100 × FIO2/PaO2 only if 100 × FIO2/PaO2 was missing, or using d100 × FIO2/PaO2 values exclusively, resulted in a small but statistically significant improvements in discrimination of Pediatric Index of Mortality 3 (area under the receiver operator curve 0.9068 [0. 8965-0. 9171]; 0.9083 [0.8981-0.9184]; 0.9087 [0.8987-0.9188], respectively). Conclusions Imputation of the PaO2/FIO2 ratio in cases where arterial sampling was not performed resulted in a large reduction in the rate of missing data if all values of SpO2 were included. The imputation technique improved the discrimination of Pediatric Index of Mortality 3; however, the magnitude of the increment in overall model performance was small. A possible benefit of the approach is reducing the potential for bias resulting from variation in practice for invasive monitoring of oxygenation.

The definitions of sepsis and septic shock have recently been revised in adults, but contemporary data are needed to inform similar approaches in children.Multicenter cohort study including children16 years admitted with sepsis or septic shock to ICUs in Australia and New Zealand in the period 2012-2015. We assessed septic shock criteria at ICU admission to define sepsis severity, using 30-day mortality as outcome. Through multivariable logistic regression, a pediatric sepsis score was derived using variables available within 60 min of ICU admission.Of 42,523 pediatric admissions, 4403 children were admitted with invasive infection, including 1697 diagnosed as having sepsis/septic shock on admission. Mortality was 8.5% (144/1697) and 50.7% of deaths occurred within 48 h of admission. The presence of septic shock as defined by the 2005 consensus was sensitive but not specific in predicting mortality (AUC = 0.69; 95% CI 0.65-0.72). Combinations of hypotension, vasopressor therapy, and lactate2 mmol/l discriminated poorly (AUC0.60). Multivariate models showed that oxygenation markers, ventilatory support, hypotension, cardiac arrest, serum lactate, pupil responsiveness, and immunosuppression were the best-performing predictors (0.843; 0.811-0.875). We derived a pediatric sepsis score (0.817; 0.779-0.855), and every one-point increase was associated with a 28.5% (23.8-33.2%) increase in the odds of death. Children with a score ≥6 had 19.8% mortality and accounted for 74.3% of deaths. The sepsis score performed comparably when applied to all children admitted with invasive infection (0.810; 0.781-0.840).We observed mortality patterns specific to pediatric sepsis that support the need for specialized definitions of sepsis severity in children. We demonstrated the importance of lactate, cardiovascular, and respiratory derangements at ICU admission for the identification of children with substantially higher risk of sepsis mortality.

Objectives: To describe the incidence and mortality of invasive infections in Indigenous children admitted to paediatric and general intensive care units (ICUs) in Australia. Design: Retrospective multi-centre cohort study of Australian and New Zealand Paediatric Intensive Care Registry data. Participants: All children under 16 years of age admitted to an ICU in Australia, 1 January 2002 e 31 December 2013. Indigenous children were defined as those identified as Aboriginal and/or Torres Strait Islander in a mandatory admissions dataset. Main outcomes: Population-based ICU mortality and admission rates. Results: Invasive infections accounted for 23.0% of non-elective ICU admissions of Indigenous children (726 of 3150), resulting in an admission rate of 47.6 per 100 000 children per year. Staphylococcus aureus was the leading pathogen identified in children with sepsis/septic shock (incidence, 4.42 per 100 000 Indigenous children per year; 0.57 per 100 000 non-Indigenous children per year; incidence rate ratio 7.7; 95% CI, 5.8-10.1; P < 0.001). While crude and risk-adjusted ICU mortality related to invasive infections was not significantly different for Indigenous and non-Indigenous children (odds ratio, 0.75; 95% CI, 0.53-1.07; P = 0.12), the estimated population-based age-standardised mortality rate for invasive infections was significantly higher for Indigenous children (2.67 per 100 000 per year v 1.04 per 100 000 per year; crude incidence rate ratio, 2.65; 95% CI, 1.88e3.64; P < 0.001). Conclusions: The ICU admission rate for severe infections was several times higher for Indigenous than for non-Indigenous children, particularly for S. aureus infections. While ICU case fatality rates were similar, the population-based mortality was more than twice as high for Indigenous children. Our study highlights an important area of inequality in health care for Indigenous children in a high income country that needs urgent attention.

Background Outcomes for pediatric cardiac surgery are commonly reported from international databases compiled from voluntary data submissions. Surgical outcomes for all children in a country or region are less commonly reported. We aimed to describe the bi‐national population‐based outcome for children undergoing cardiac surgery in Australia and New Zealand and determine whether the Risk Adjustment for Congenital Heart Surgery ( RACHS ) classification could be used to create a model that accurately predicts in‐hospital mortality in this population. Methods and Results The study was conducted in all children's hospitals performing cardiac surgery in Australia and New Zealand between January 2007 and December 2015. The performance of the original RACHS ‐1 model was assessed and compared with an alternative RACHS ‐ ANZ (Australia and New Zealand) model, developed balancing discrimination with parsimonious variable selection. A total of 14 324 hospital admissions were analyzed. The overall hospital mortality was 2.3%, ranging from 0.5% for RACHS category 1 procedures, to 17.0% for RACHS category 5 or 6 procedures. The original RACHS ‐1 model was poorly calibrated with death overpredicted (1161 deaths predicted, 289 deaths observed). The RACHS ‐ ANZ model had better performance in this population with excellent discrimination (Az‐ ROC of 0.830) and acceptable Hosmer and Lemeshow goodness‐of‐fit ( P =0.216). Conclusions The original RACHS ‐1 model overpredicts mortality in children undergoing heart surgery in the current era. The RACHS ‐ ANZ model requires only 3 risk variables in addition to the RACHS procedure category, can be applied to a wider range of patients than RACHS ‐1, and is suitable to use to monitor regional pediatric cardiac surgery outcomes.

Objective: Outcomes for children with chronic critical illness are not defined. We examined the long-term survival of these children in Australia and New Zealand.

Objectives: Despite World Health Organization endorsed immunization schedules, Bordetella pertussis continues to cause severe infections, predominantly in infants. There is a lack of data on the frequency and outcome of severe pertussis infections in infants requiring ICU admission. We aimed to describe admission rates, severity, mortality, and costs of pertussis infections in critically ill infants. Design: Binational observational multicenter study. Setting: Ten PICUs and 19 general ICUs in Australia and New Zealand contributing to the Australian and New Zealand Paediatric Intensive Care Registry. Patients: Infants below 1 year of age, requiring intensive care due to pertussis infection in Australia and New Zealand between 2002 and 2014. Measurements and Main Results: During the study period, 416 of 42,958 (1.0%) infants admitted to the ICU were diagnosed with pertussis. The estimated population-based ICU admission rate due to pertussis ranged from 2.1/100,000 infants to 18.6/100,000 infants. Admission rates were the highest among infants less than 60 days old (p < 0.0001). Two hundred six infants (49.5%) required mechanical ventilation, including 20 (4.8%) treated with high-frequency oscillatory ventilation, 16 (3.8%) with inhaled nitric oxide, and 7 (1.7%) with extracorporeal membrane oxygenation. Twenty of the 416 children (4.8%) died. The need for mechanical ventilation, high-frequency oscillatory ventilation, nitric oxide, and extracorporeal membrane oxygenation were significantly associated with mortality (p < 0.01). Direct severe pertussis-related hospitalization costs were in excess of USD$1,000,000 per year. Conclusions: Pertussis continues to cause significant morbidity and mortality in infants, in particular during the first months of life. Improved strategies are required to reduce the significant healthcare costs and disease burden of this vaccine-preventable disease.

To describe the temporal trends in rates of PICU admissions and mortality for out-of-hospital cardiac arrests and in-hospital cardiac arrests admitted to PICU over the last decade.Multicenter, retrospective analysis of prospectively collected binational data of the Australian and New Zealand Paediatric Intensive Care Registry. All nine specialist PICUs in Australia and New Zealand were included.All children admitted between 2003 and 2012 to PICU who were less than 16 years old at the time of admission.None.There were a total of 71,425 PICU admissions between 2003 and 2012. Overall, cardiac arrest accounted for 1.86% of all admissions (1,329 cases), including 677 cases of in-hospital cardiac arrest (51.0%) and 652 cases of out-of-hospital cardiac arrest (49.0%). Over the last decade, there has been a 29.6% increase in the odds of PICU survival for all pediatric admissions (odds ratio, 1.30; 95% CI, 1.09-1.54). By contrast, there was no significant improvement in the risk-adjusted odds of survival for out-of-hospital cardiac arrest admissions (odds ratio, 1.03; 95% CI, 0.50-2.10; p = 0.94) or in-hospital cardiac arrest admissions (odds ratio, 1.03; 95% CI, 0.54-1.98; p = 0.92).Despite improvements in overall outcomes in children admitted to Australian and New Zealand PICUs, survival of children admitted with out-of-hospital cardiac arrest or in-hospital cardiac arrest did not change significantly over the past decade.

We conducted a meta-analysis to assess the performance of PCR for the diagnosis of smear-negative pulmonary tuberculosis (SPT) and to identify factors that account for differences in the diagnostic accuracy of different studies. Studies published before February 2002 were included if sensitivity and specificity of PCR in smear-negative respiratory or gastric-aspirate specimens could be calculated. Analysis was conducted by using summary receiver operating characteristics models. Sensitivity and specificity ranged from 9 to 100% and from 25 to 100%, respectively. Fewer than 40% of the 50 studies reported results by number of patients, reported clinical characteristics of patients, or used as a reference standard combined culture and clinical criteria. Studies that included bronchial specimens showed higher accuracy than studies that evaluated only sputum specimens or included gastric aspirates. Studies that did not report that tests were applied blindly showed higher accuracy than those reporting blind testing. Increased sensitivity due to the use of DNA purification methods was associated with decreased specificity. Studies published after 1995, using Amplicor or dUTP-UNG, were associated with an increase in specificity at the expense of lower sensitivity. We concluded that PCR is not consistently accurate enough to be routinely recommended for the diagnosis of SPT. However, PCR of bronchial specimens could be useful in highly suspicious SPT cases. Studies not reporting blind testing are likely to overestimate accuracy of PCR. Future evaluation of PCR accuracy should be conducted by patient and type of respiratory specimen, blindly, by using a reference standard that combines culture and clinical criteria and addresses the issue of how patient characteristics affect PCR accuracy.

Bronchiolitis represents the most common cause of non-elective admission to paediatric intensive care units (ICUs).We assessed changes in admission rate, respiratory support, and outcomes of infants During the study period, bronchiolitis was responsible for 9628 (27.6%) of 34 829 non-elective ICU admissions. The estimated population-based ICU admission rate due to bronchiolitis increased by 11.76 per 100 000 each year (95% CI 8.11–15.41). The proportion of bronchiolitis patients requiring intubation decreased from 36.8% in 2002, to 10.8% in 2014 (adjusted OR 0.35, 95% CI 0.27–0.46), whilst a dramatic increase in high-flow nasal cannula therapy use to 72.6% was observed (pWe observed an increasing healthcare burden due to severe bronchiolitis, with a major change in practice in the management from invasive to non-invasive support that suggests thresholds to admittance of bronchiolitis patients to ICU have changed. Future studies should assess strategies for management of bronchiolitis outside ICUs.

Summary Background Severe infections kill more than 4·5 million children every year. Population-based data for severe infections in children requiring admission to intensive care units (ICUs) are scarce. We assessed changes in incidence and mortality of severe infections in critically ill children in Australia and New Zealand. Methods We did a retrospective multicentre cohort study of children requiring intensive care in Australia and New Zealand between 2002 and 2013, with data from the Australian and New Zealand Paediatric Intensive Care Registry. We included children younger than 16 years with invasive infection, sepsis, or septic shock. We assessed incidence and mortality in the ICU for 2002–07 versus 2008–13. Findings During the study period, 97 127 children were admitted to ICUs, 11 574 (11·9%) had severe infections, including 6688 (6·9%) with invasive infections, 2847 (2·9%) with sepsis, and 2039 (2·1%) with septic shock. Age-standardised incidence increased each year by an average of 0·56 cases per 100 000 children (95% CI 0·41–0·71) for invasive infections, 0·09 cases per 100 000 children (0·00–0·17) for sepsis, and 0·08 cases per 100 000 children (0·04–0·12) for septic shock. 260 (3·9%) of 6688 patients with invasive infection died, 159 (5·6%) of 2847 with sepsis died, and 346 (17·0%) of 2039 with septic shock died, compared with 2893 (3·0%) of all paediatric ICU admissions. Children admitted with invasive infections, sepsis, and septic shock accounted for 765 (26·4%) of 2893 paediatric deaths in ICUs. Comparing 2008–13 with 2002–07, risk-adjusted mortality decreased significantly for invasive infections (odds ratio 0·72, 95% CI 0·56–0·94; p=0·016), and for sepsis (0·66, 0·47–0·93; p=0·016), but not significantly for septic shock (0·79, 0·61–1·01; p=0·065). Interpretation Severe infections remain a major cause of mortality in paediatric ICUs, representing a major public health problem. Future studies should focus on patients with the highest risk of poor outcome, and assess the effectiveness of present sepsis interventions in children. Funding National Medical Health and Research Council, Australian Resuscitation Outcomes Consortium, Centre of Research Excellence (1029983).

To provide an updated version of the Paediatric Index of Mortality 2 for assessing the risk of mortality among children admitted to an ICU.International, multicenter, prospective cohort study.Sixty ICUs that accept pediatric admissions in Australia, New Zealand, Ireland, and the United Kingdom.All children admitted in 2010 and 2011 younger than 18 years old at the time of admission and either died in ICU or were discharged. Patients who were transferred to another ICU were not included. Fifty-three thousand one hundred twelve patient admissions were included in the analysis.None.A revised prediction model was built using logistic regression. Variable selection was based on significance at the 95% level and overall improvement of the model's discriminatory performance and goodness of fit. The final model discriminated well (area under the curve, 0.88, 0.88-0.89); however, the model performed better in Australia and New Zealand than in the United Kingdom and Ireland (area under the curve was 0.91, 0.90-0.93 and 0.85, 0.84-0.86, respectively).Paediatric Index of Mortality 3 provides an international standard based on a large contemporary dataset for the comparison of risk-adjusted mortality among children admitted to intensive care.

Objective: To test the effect of substituting a modified-fat cheese product into the diets of hypercholesterolemic adults. Design: A 4-month, randomized, double-blind, crossover substitution trial....

We investigated the relationship between cutaneous malignant melanoma and multiple sunburns in the Queensland population. Interview data were gathered from 236 case-control pairs concerning their lifetime experience of severe sunburns, their occupational and recreational sun exposure, and their skin type. Excluding the lentigo maligna melanoma subtype, an association between multiple sunburns and melanoma was evident. After controlling for other major risk factors there was a significant dose-response relationship (P less than 0.05): the estimated relative risk associated with 2-5 sunburns in life was 1.5, and with 6 or more was 2.4. This observation extends the hitherto circumstantial evidence of a causal relationship between exposure to solar ultraviolet radiation and melanoma, and suggests that precautionary measures could prevent the development of this disease in a proportion of cases in fair-skinned populations.

Background Australia uses acute flaccid paralysis (AFP) surveillance to monitor its polio-free status. The World Health Organization criterion for a sensitive AFP surveillance system is the annual detection of at least one non-polio AFP case per 100,000 children aged less than 15 years, a target Australia has not consistently achieved. Children exhibiting AFP are likely to be hospitalised and may be admitted to an intensive care unit. This provides a potential opportunity for active AFP surveillance. Methods A data-linkage study for the period from 1 January 2005 to 31 December 2008 compared 165 non-polio AFP cases classified by the Polio Expert Panel with 880 acute neurological presentations potentially compatible with AFP documented in the Australian and New Zealand Paediatric Intensive Care (ANZPIC) Registry. Results Forty-two (25%) AFP cases classified by the Polio Expert Panel were matched to case records in the ANZPIC Registry. Of these, nineteen (45%) cases were classified as Guillain-Barré syndrome on both registries. Ten additional Guillain-Barré syndrome cases recorded in the ANZPIC Registry were not notified to the national AFP surveillance system. Conclusions The identification of a further ten AFP cases supports inclusion of intensive care units in national AFP surveillance, particularly specialist paediatric intensive care units, to identify AFP cases that may not otherwise be reported to the national surveillance system.