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Background: Investigation of infection risk with subcutaneous versus intravenous trastuzumab and rituximab administration in an individual patient data (IPD) and published data meta-analysis of randomised controlled trials (RCTs). Methods: Databases were searched to September 2021. Primary outcomes were serious and high-grade infection. Relative-risk (RR) and 95% confidence intervals (95%CI) were calculated using random-effects models. Results: IPD meta-analysis (6 RCTs, 2971 participants, 2320 infections) demonstrated higher infection incidence with subcutaneous versus intravenous administration, without reaching statistical significance (serious: 12.2% versus 9.3%, RR 1.28, 95%CI 0.93to1.77, P = 0.13; high-grade: 12.2% versus 9.9%, RR 1.32, 95%CI 0.98to1.77, P = 0.07). With exclusion of an outlying study in post-hoc analysis, increased risks were statistically significant (serious: 13.1% versus 8.4%, RR 1.53, 95%CI 1.14to2.06, P = 0.01; high-grade: 13.2% versus 9.3%, RR 1.56, 95%CI 1.16to2.11, P < 0.01). Published data meta-analysis (8 RCTs, 3745 participants, 648 infections) demonstrated higher incidence of serious (HR 1.31, 95%CI 1.02to1.68, P = 0.04) and high-grade (HR 1.52, 95%CI 1.17to1.98, P < 0.01) infection with subcutaneous versus intravenous administration. Conclusions: Results suggest increased infection risk with subcutaneous versus intravenous administration, although IPD findings are sensitive to exclusion of one trial with inconsistent results and identified risk-of-bias. Ongoing trials may confirm findings. Clinical surveillance should be considered when switching to subcutaneous administration. PROSPERO registration CRD42020221866/CRD42020125376. [ABSTRACT FROM AUTHOR]

This study used a prospective community-based sample to describe patterns and predictors of language development from 4 to 7 years in verbal children (IQ = 70) with autism spectrum disorder (ASD; n = 26-27). Children with typical language (TD; n = 858-861) and language impairment (LI; n = 119) were used for comparison. Children with ASD and LI had similar mean language scores that were lower on average than children with TD. Similar proportions across all groups had declining, increasing and stable patterns. Language progressed at a similar rate for all groups, with progress influenced by IQ and language ability at 4 years rather than social communication skills or diagnosis of ASD. These findings inform advice for parents about language prognosis in ASD.

This study used a prospective community-based sample to describe patterns and predictors of language development from 4 to 7 years in verbal children (IQ [greater than or equal to] 70) with autism spectrum disorder (ASD; n = 26-27). Children with typical language (TD; n = 858-861) and language impairment (LI; n = 119) were used for comparison. Children with ASD and LI had similar mean language scores that were lower on average than children with TD. Similar proportions across all groups had declining, increasing and stable patterns. Language progressed at a similar rate for all groups, with progress influenced by IQ and language ability at 4 years rather than social communication skills or diagnosis of ASD. These findings inform advice for parents about language prognosis in ASD., Author(s): Amanda Brignell [sup.1] [sup.2] , Katrina Williams [sup.1] [sup.2] [sup.3] , Kim Jachno [sup.2] , Margot Prior [sup.1] , Sheena Reilly [sup.4] , Angela T. Morgan [sup.1] [sup.2] Author [...]

Aim: The prevalence of chronic kidney disease (CKD) in the elderly is controversial because age‐related decline in kidney function may not truly reflect underlying kidney disease. We estimate the baseline prevalence and predictors of CKD using the CKD Epidemiology Collaboration (CKD‐EPIeGFR) and Berlin Initiative Study 1 (BIS1eGFR) eGFR equations in the ASPirin in Reducing Events in the Elderly (ASPREE) trial cohort of healthy older participants. Methods: GFR was estimated using CKD‐EPI and BIS1 equations. CKD was defined as eGFR <60 mL/min/1.73 m2 or ≥ 60 mL/min/1.73 m2 with urine albumin creatinine ratio (UACR) ≥ 3 mg/mmol. Logistic regression was used to identify predictors of CKD prevalence defined by each eGFR equation. Results: Data for analysis were complete for 17,762 participants. Mean age was 75.1 years (SD 5); 56.4% were female, 76.4% had hypertension, 9% had diabetes mellitus. Mean CKD‐EPIeGFR was 73.0 (SD 14.2), compared with mean BIS1eGFR of 62.7 (11.4). Median UACR was 0.8 (IQR 0.5, 1.5) mg/mmol. Prevalence of CKD by CKD‐EPIeGFR was 27% (predominantly due to normoalbuminuric stage 3a CKD), substantially lower than 47.1% by BIS1eGFR; the difference was predominantly driven by reclassification of individuals from G1 and G2 CKD to stage G3a without albuminuria. Increased prevalence of CKD by either equation was related to older age, hypertension, diabetes, or higher body mass index. Conclusions: Prevalence of CKD with CKD‐EPIeGFR was 27%, and doubled using the elderly specific BIS1eGFR, with most participants reclassified from stage 2 to stage 3a. Increased prevalence of CKD was related older age, hypertension, diabetes, or increased body mass index. SUMMARY AT A GLANCE: Chronic kidney disease (CKD) is common and increases with age even in healthy elderly people. The elderly specific Berlin Initiative Study 1 (BIS1eGFR) estimated glomerular filtration rate (eGFR) equation BIS1eGFR substantially increases CKD prevalence, largely by reclassifying elderly participants from G1 and G2 CKD to stage G3a without albuminuria to stage 3a CKD. [ABSTRACT FROM AUTHOR]

Recently, we observed a 15% decrease in the incidence of type 1 diabetes (T1D) in Australian 0-4-year-old children following the introduction of RV vaccination [[2], [3]], suggesting that RV vaccination could contribute to the primary prevention of this autoimmune disease. Australian surveillance data [[11]] show that the prevalence of RV G3 strains increased slightly along with an increase in strain diversity in the post-RV vaccine era, but G3 remains a minor component of disease-causing RV strains. RV was prevalent in nurseries, and the change to rooming-in would have altered the timing of exposure to RV, delaying it until later in the first year of life when, based on NOD mouse studies [[17]-[19]], RV might promote rather than retard development of diabetes. [Extracted from the article]

Background: There are no medications known that improve the outcome of infants with bronchiolitis. Studies have shown the management of bronchiolitis to be varied. Objectives: To describe medication use at the seven study hospitals from a recent multi-centre randomised controlled trial on hydration in bronchiolitis (comparative rehydration in bronchiolitis [CRIB]). Methods: A retrospective analysis of extant data of infants between 2 months (corrected for prematurity) and 12 months of age admitted with bronchiolitis identified through the CRIB trial. CRIB study records, medical records, pathology and radiology databases were used to collect data using a standardised form and entered in a single site database. Medications investigated included salbutamol, adrenaline, steroids, ipratropium bromide, normal saline, hypertonic saline, steroids and antibiotics. Results: There were 3456 infants available for analysis, of which 42.0% received at least one medication during hospitalisation. Medication use varied by site between 27.0 and 48.7%. The most frequently used medication was salbutamol (25.5%). Medication use in general, and salbutamol use in particular, increased by 8.2 and 9.3%, respectively, per month after 4 months of age; from 22.9 and 3.6% at 4 months to 81.4 and 68.8% at 11 months. In infants admitted to the intensive care unit (ICU) compared with those not admitted to ICU 81.6 and 39.5%, respectively, received medication at one point during the hospital stay. Conclusions: Medication was used for infants with bronchiolitis frequently and variably in Australia and New Zealand. Medication use increased with age. Better strategies for translating evidence into practice are needed. [ABSTRACT FROM AUTHOR]

Aim: We aimed to examine the impact of weather on hospital admissions with bronchiolitis in Australia and New Zealand.Methods: We collected data for inpatient admissions of infants aged 2-12 months to seven hospitals in four cities in Australia and New Zealand from 2009 until 2011. Correlation of hospital admissions with minimum daily temperature, wind speed, relative humidity and rainfall was examined using linear, Poisson and negative binomial regression analyses as well as general estimated equation models. To account for possible lag between exposure to weather and admission to hospital, analyses were conducted for time lags of 0-4 weeks.Results: During the study period, 3876 patients were admitted to the study hospitals. Hospital admissions showed strong seasonality with peaks in wintertime, onset in autumn and offset in spring. The onset of peak incidence was preceded by a drop in temperature. Minimum temperature was inversely correlated with hospital admissions, whereas wind speed was directly correlated. These correlations were sustained for time lags of up to 4 weeks. Standardised correlation coefficients ranged from -0.14 to -0.54 for minimum temperature and from 0.18 to 0.39 for wind speed. Relative humidity and rainfall showed no correlation with hospital admissions in our study.Conclusion: A decrease in temperature and increasing wind speed are associated with increasing incidence of bronchiolitis hospital admissions in Australia and New Zealand. [ABSTRACT FROM AUTHOR]

Objectives To describe the rate of intensive care unit (ICU) admission, type of ventilation support provided and risk factors for ICU admission in infants with bronchiolitis. Design Retrospective review of hospital records and Australia and New Zealand Paediatric Intensive Care (ANZPIC) registry data for infants 2-12 months old admitted with bronchiolitis. Setting Seven Australian and New Zealand hospitals. These infants were prospectively identified through the comparative rehydration in bronchiolitis (CRIB) study between 2009 and 2011. Results Of 3884 infants identified, 3589 charts were available for analysis. Of 204 (5.7%) infants with bronchiolitis admitted to ICU, 162 (79.4%) received ventilation support. Of those 133 (82.1%) received non-invasive ventilation (high flow nasal cannula [HFNC] or continuous positive airway pressure [CPAP]) 7 (4.3%) received invasive ventilation alone and 21 (13.6%) received a combination of ventilation modes. Infants with comorbidities such as chronic lung disease (OR 1.6 [95% CI 1.0-2.6]), congenital heart disease (OR 2.3 [1.5-3.5]), neurological disease (OR 2.2 [1.2-4.1]) or prematurity (OR 1.5 [1.0-2.1]), and infants 2-6 months of age (OR 1.5 [1.1-2.0]) were more likely to be admitted to ICU. Respiratory syncitial virus positivity did not increase the likelihood of being admitted to ICU (OR 1.1 [95% CI 0.8-1.4]). HFNC use changed from 13/53 (24.5% [95% CI 13.7-38.3]) patient episodes in 2009 to 39/91 (42.9% [95% CI 32.5-53.7]) patient episodes in 2011. Conclusion Admission to ICU is an uncommon occurrence in infants admitted with bronchiolitis, but more common in infants with comorbidities and prematurity. The majority are managed with non-invasive ventilation, with increasing use of HFNC. [ABSTRACT FROM AUTHOR]

Objective Bronchiolitis is the most common lower respiratory tract infection in infants and the leading cause of hospitalisation. We aimed to assess whether intravenous hydration ( IVH) was more cost-effective than nasogastric hydration ( NGH) as a planned secondary economic analysis of a randomised trial involving 759 infants (aged 2-12 months) admitted to hospital with a clinical diagnosis of bronchiolitis and requiring non-oral hydration. No Australian cost data exist to aid clinicians in decision-making around interventions in bronchiolitis. Methods Cost data collections included hospital and intervention-specific costs. The economic analysis was reduced to a cost-minimisation study, focusing on intervention-specific costs of IVH versus NGH, as length of stay was equal between groups. All analyses are reported as intention to treat. Results Intervention costs were greater for IVH than NGH ($113 vs $74; cost difference of $39 per child). The intervention-specific cost advantage to NGH was robust to inter-site variation in unit prices and treatment activity. Conclusion Intervention-specific costs account for <10% of total costs of bronchiolitis admissions, with NGH having a small cost saving across all sites. [ABSTRACT FROM AUTHOR]

Objective Paediatric head injury is a common presentation to the ED. North American studies demonstrate increasing use of computed tomography (CT) brain scan (CTB) to investigate head injury. No such data exists for Australian EDs. The aim of this study was to describe CTB use in head injury over time in eight Australian EDs. Methods Retrospective ED electronic database and medical imaging database audit was undertaken for the years 2001-2010 by International Classification of Diseases (ICD) 9 or 10 code for head injury in children <16 years. EDs and medical imaging departments of eight hospitals in Australia (five tertiary referral and three mixed departments). Data for ED presentations with head injury, and all CTB performed by medical imaging were merged to obtain a data set of CTB performed within 24 h for head injury-related attendances to the ED. Descriptive and comparative analysis of CTB rates was performed. Results The rate of CTB over the decade was 10.2% (95% confidence interval (CI) 9.9-10.5). The annual rate varied from 9.5% (95% CI 8.2-10.9) to 12.5% (95% CI 11.2-13.9). CTB use did not increase over time. Median year of age at time of CT scan was 4 years, with an interquartile range of 1.5-9.4 years. Overall there was a 9.2% increase in the CTB scan rate for every additional year of age at presentation (95% CI 6.6-12.1; P < 0.001). Conclusion CTB use in head injuries did not increase during the study period, and rates of CTB were less than reported for North America. [ABSTRACT FROM AUTHOR]

The modern environment is associated with an increasing burden of non-communicable diseases (NCDs). Mounting evidence implicates environmental exposures, experienced early in life (including in utero), in the aetiology of many NCDs, though the cellular/molecular mechanism(s) underlying this elevated risk across the life course remain unclear. Epigenetic variation has emerged as a candidate mediator of such effects. The Barwon Infant Study (BIS) is a population-derived birth cohort study (n = 1074 infants) with antenatal recruitment, conducted in the south-east of Australia (Victoria). BIS has been designed to facilitate a detailed mechanistic investigation of development within an epidemiological framework. The broad objectives are to investigate the role of specific environmental factors, gut microbiota and epigenetic variation in early-life development, and subsequent immune, allergic, cardiovascular, respiratory and neurodevelopmental outcomes. Participants have been reviewed at birth and at 1, 6, 9 and 12 months, with 2- and 4-year reviews under way. Biological samples and measures include: maternal blood, faeces and urine during pregnancy; infant urine, faeces and blood at regular intervals during the first 4 years; lung function at 1 month and 4 years; cardiovascular assessment at 1 month and 4 years; skin-prick allergy testing and food challenge at 1 year; and neurodevelopmental assessment at 9 months, 2 and 4 years. Data access enquiries can be made at [www.barwoninfantstudy.org.au] or via [peter.vuillermin@deakin.edu.au]. [ABSTRACT FROM AUTHOR]

Background Head injuries in children are responsible for a large number of emergency department visits. Failure to identify a clinically significant intracranial injury in a timely fashion may result in long term neurodisability and death. Whilst cranial computed tomography (CT) provides rapid and definitive identification of intracranial injuries, it is resource intensive and associated with radiation induced cancer. Evidence based head injury clinical decision rules have been derived to aid physicians in identifying patients at risk of having a clinically significant intracranial injury. Three rules have been identified as being of high quality and accuracy: the Canadian Assessment of Tomography for Childhood Head Injury (CATCH) from Canada, the Children's Head Injury Algorithm for the Prediction of Important Clinical Events (CHALICE) from the UK, and the prediction rule for the identification of children at very low risk of clinically important traumatic brain injury developed by the Pediatric Emergency Care Applied Research Network (PECARN) from the USA. This study aims to prospectively validate and compare the performance accuracy of these three clinical decision rules when applied outside the derivation setting. Methods/design This study is a prospective observational study of children aged 0 to less than 18 years presenting to 10 emergency departments within the Paediatric Research in Emergency Departments International Collaborative (PREDICT) research network in Australia and New Zealand after head injuries of any severity. Predictor variables identified in CATCH, CHALICE and PECARN clinical decision rules will be collected. Patients will be managed as per the treating clinicians at the participating hospitals. All patients not undergoing cranial CT will receive a follow up call 14 to 90 days after the injury. Outcome data collected will include results of cranial CTs (if performed) and details of admission, intubation, neurosurgery and death. The performance accuracy of each of the rules will be assessed using rule specific outcomes and inclusion and exclusion criteria. Discussion This study will allow the simultaneous comparative application and validation of three major paediatric head injury clinical decision rules outside their derivation setting. [ABSTRACT FROM AUTHOR]

Background Aortic intima-media thickness measured by transabdominal ultrasound (aIMT) is an intermediate phenotype of cardiovascular risk. We aimed to (1) investigate the reproducibility of aIMT in a population-derived cohort of infants; (2) establish the distribution of aIMT in early infancy; (3) compare measurement by edge-detection software to that by manual sonographic calipers; and (4) assess the effect of individual and environmental variables on image quality. Methods Participants were term infants recruited to a population-derived birth cohort study. Transabdominal ultrasound was performed at six weeks of age by one of two trained operators. Thirty participants had ultrasounds performed by both operators on the same day. Data were collected on environmental (infant sleeping, presence of a sibling, use of sucrose, timing during study visit) and individual (post-conception age, weight, gender) variables. Two readers assessed image quality and measured aIMT by edge-detection software and a subset by manual sonographic calipers. Measurements were repeated by the same reader and between readers to obtain intra-observer and inter-observer reliability. Results Aortic IMT was measured successfully using edge-detection in 814 infants, and 290 of these infants also had aIMT measured using manual sonographic calipers. The intra-reader intraclass correlation (ICC) (n = 20) was 0.90 (95%CI 0.76, 0.96), mean difference 1.5 μm (95%LOA -39, 59). The between reader ICC using edge-detection (n = 20) was 0.92 (95%CI 0.82, 0.97) mean difference 2 μm (95%LOA -45.0, 49.0) and with manual caliper measurement (n = 290) the ICC was 0.84 (95%CI 0.80, 0.87) mean difference 5 μm (95%LOA -51.8, 61.8). Edge-detection measurements were greater than those from manual sonographic calipers (mean aIMT 618 μm (50) versus mean aIMT 563 μm (49) respectively; p < 0.001, mean difference 44 μm, 95%LOA -54, 142). With the exception of infant crying (p = 0.001), no associations were observed between individual and environmental variables and image quality. Conclusion In a population-derived cohort of term infants, aIMT measurement has a high level of intra and inter-reader reproducibility. Measurement of aIMT using edge-detection software gives higher inter-reader ICC than manual sonographic calipers. Image quality is not substantially affected by individual and environmental factors. [ABSTRACT FROM AUTHOR]

Summary: Background: Bronchiolitis is the most common lower respiratory tract infection in infants and the leading cause of hospital admission. Hydration is a mainstay of treatment, but insufficient evidence exists to guide clinical practice. We aimed to assess whether intravenous hydration or nasogastric hydration is better for treatment of infants. Methods: In this multicentre, open, randomised trial, we enrolled infants aged 2–12 months admitted to hospitals in Australia and New Zealand with a clinical diagnosis of bronchiolitis during three bronchiolitis seasons (April 1–Oct 31, in 2009, 2010, and 2011). We randomly allocated infants to nasogastric hydration or intravenous hydration by use of a computer-generated sequence and opaque sealed envelopes, with three randomly assigned block sizes and stratified by hospital site and age group (2–<6 months vs 6–12 months). The primary outcome was length of hospital stay, assessed in all randomly assigned infants. Secondary outcomes included rates of intensive-care unit admission, adverse events, and success of insertion. This trial is registered with the Australian and New Zealand clinical trials registry, ACTRN12605000033640. Findings: Mean length of stay for 381 infants assigned nasogastric hydration was 86·6 h (SD 58·9) compared with 82·2 h (58·8) for 378 infants assigned intravenous hydration (absolute difference 4·5 h [95% CI −3·9 to 12·9]; p=0·30). Rates of admission to intensive-care units, need for ventilatory support, and adverse events did not differ between groups. At randomisation, seven infants assigned nasogastric hydration were switched to intravenous hydration and 56 infants assigned intravenous hydration were switched to nasogastric hydration because the study-assigned method was unable to be inserted. For those infants who had data available for successful insertion, 275 (85%) of 323 infants in the nasogastric hydration group and 165 (56%) of 294 infants in the intravenous hydration group required only one attempt for successful insertion. Interpretation: Intravenous hydration and nasogastric hydration are appropriate means to hydrate infants with bronchiolitis. Nasogastric insertion might require fewer attempts and have a higher success rate of insertion than intravenous hydration. Funding: Australian National Health and Medical Research Council, Samuel Nissen Charitable Foundation (Perpetual), Murdoch Children's Research Institute, Victorian Government. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to describe antibiotic exposure in Australian infants during the first year of life, focusing on antibiotic class, indication, risk factors associated with exposure and comparison with international counterparts.Methods: The Barwon Infant Study is a birth cohort study (n = 1074) with an unselected antenatal sampling frame from a large regional centre in Victoria, Australia. Longitudinal data on infection and medication were collected at 1, 3, 6, 9 and 12 months by parental questionnaire and from general practitioner and hospital records. Predictors of questionnaire non-completion were identified. A total of 660 infants with complete serial data were comprehensively examined. Antibiotic exposure was calculated as (i) antibiotic prescriptions and (ii) antibiotic days-exposed per person-year.Results: Mean antibiotic prescription rate was 0.92 prescriptions (95% confidence interval (CI), 0.83-1.02) per person-year, with the highest rates in those aged <1 month (1.50 (95% CI, 1.09-1.91) per person-year). A total of 50.0% of infants were exposed to at least one antibiotic in their first year of life. Increasing number of siblings was associated with increased antibiotic exposure. Penicillin with extended spectrum (365 of 661 antibiotic prescriptions, 52.6%) and cephalosporins (12.0%) were the most frequently prescribed antibiotics. One fifth of antibiotics were prescribed for respiratory tract infections and bronchiolitis.Conclusion: Australian infants in this large population-based study are exposed to considerably more antibiotics than the majority of their international counterparts. Interventions aimed at addressing avoidable prescribing by medical practitioners and modifiable risk factors associated with antibiotic exposure may reduce antibiotic use. [ABSTRACT FROM AUTHOR]