Learning outcomes from a systematic review workshop series for junior doctors.

BACKGROUND: Systematic reviews provide the highest level of evidence about a topic. Ten-week workshops in conducting systematic reviews were held with hospital doctors in 2019 and 2020. AIM: This study analysed participants' feedback about the systematic review workshops to improve how we teach clinicians about conducting systematic reviews. METHODS: Attendees completed a post-workshop survey (with multiple-choice and free-text items) to assess knowledge and skills gained. We compared the responses of senior and junior doctors. We used descriptive statistics for the quantitative data and compared groups using Χ2 testing. Qualitative data were analysed using conceptual content analysis. RESULTS: Of 81 attendees, 52% completed the survey. Of those, 69% had no prior experience with systematic reviews, 93% reported increased knowledge and ability to conduct research and 69% reported increased ability to conduct systematic reviews. More senior than junior clinicians reported gaining knowledge about writing and publishing (37% vs 11%, P = 0.047) and making greater use of skills gained to conduct research (56% vs 23%, P = 0.029). Five themes were identified: learning through course structure; learning through course organisation; teaching style; flexible learning; and suggestions for progression and improvement. Respondents suggested running the workshops during protected teaching time, more time for some sessions, conducting the workshop series more often and making clinicians aware of the workshop series at hospital orientation. CONCLUSION: The skills learnt from the systematic review workshop series impacted not only participants' research knowledge and skills, and plans to conduct future research, but also facilitated looking up medical literature in daily clinical work, supporting evidence-based clinical practice.

Adjuvant chemotherapy following chemoradiotherapy as primary treatment for locally advanced cervical cancer versus chemoradiotherapy alone (OUTBACK): an international, open-label, randomised, phase 3 trial.

BACKGROUND: Standard treatment for locally advanced cervical cancer is chemoradiotherapy, but many patients relapse and die of metastatic disease. We aimed to determine the effects on survival of adjuvant chemotherapy after chemoradiotherapy. METHODS: The OUTBACK trial was a multicentre, open-label, randomised, phase 3 trial done in 157 hospitals in Australia, China, Canada, New Zealand, Saudi Arabia, Singapore, and the USA. Eligible participants were aged 18 year or older with histologically confirmed squamous cell carcinoma, adenosquamous cell carcinoma, or adenocarcinoma of the cervix (FIGO 2008 stage IB1 disease with nodal involvement, or stage IB2, II, IIIB, or IVA disease), Eastern Cooperative Oncology Group performance status 0-2, and adequate bone marrow and organ function. Participants were randomly assigned centrally (1:1) using a minimisation approach and stratified by pelvic or common iliac nodal involvement, requirement for extended-field radiotherapy, FIGO 2008 stage, age, and site to receive standard cisplatin-based chemoradiotherapy (40 mg/m2 cisplatin intravenously once-a-week for 5 weeks, during radiotherapy with 45·0-50·4 Gy external beam radiotherapy delivered in fractions of 1·8 Gy to the whole pelvis plus brachytherapy; chemoradiotherapy only group) or standard cisplatin-based chemoradiotherapy followed by adjuvant chemotherapy with four cycles of carboplatin (area under the receiver operator curve 5) and paclitaxel (155 mg/m2) given intravenously on day 1 of a 21 day cycle (adjuvant chemotherapy group). The primary endpoint was overall survival at 5 years, analysed in the intention-to-treat population (ie, all eligible patients who were randomly assigned). Safety was assessed in all patients in the chemoradiotherapy only group who started chemoradiotherapy and all patients in the adjuvant chemotherapy group who received at least one dose of adjuvant chemotherapy. The OUTBACK trial is registered with ClinicalTrials.gov, NCT01414608, and the Australia New Zealand Clinical Trial Registry, ACTRN12610000732088. FINDINGS: Between April 15, 2011, and June 26, 2017, 926 patients were enrolled and randomly assigned to the chemoradiotherapy only group (n=461) or the adjuvant chemotherapy group (n=465), of whom 919 were eligible (456 in the chemoradiotherapy only group and 463 in the adjuvant chemotherapy group; median age 46 years [IQR 37 to 55]; 663 [72%] were White, 121 [13%] were Black or African American, 53 [6%] were Asian, 24 [3%] were Aboriginal or Pacific islander, and 57 [6%] were other races) and included in the analysis. As of data cutoff (April 12, 2021), median follow-up was 60 months (IQR 45 to 65). 5-year overall survival was 72% (95% CI 67 to 76) in the adjuvant chemotherapy group (105 deaths) and 71% (66 to 75) in the chemoradiotherapy only group (116 deaths; difference 1% [95% CI -6 to 7]; hazard ratio 0·90 [95% CI 0·70 to 1·17]; p=0·81). In the safety population, the most common clinically significant grade 3-4 adverse events were decreased neutrophils (71 [20%] in the adjuvant chemotherapy group vs 34 [8%] in the chemoradiotherapy only group), and anaemia (66 [18%] vs 34 [8%]). Serious adverse events occurred in 107 (30%) in the adjuvant chemotherapy group versus 98 (22%) in the chemoradiotherapy only group, most commonly due to infectious complications. There were no treatment-related deaths. INTERPRETATION: Adjuvant carboplatin and paclitaxel chemotherapy given after standard cisplatin-based chemoradiotherapy for unselected locally advanced cervical cancer increased short-term toxicity and did not improve overall survival; therefore, it should not be given in this setting. FUNDING: National Health and Medical Research Council and National Cancer Institute.

Clinical features associated with epilepsy occurrence, resolution, and drug resistance in children with cerebral palsy: A population-based study.

AIM: To investigate clinicoradiological features associated with epilepsy, its resolution, and drug resistance in children with cerebral palsy (CP). METHOD: Data were gathered from the New South Wales/Australian Capital Territory CP Register, encompassing children with CP born between 2003 and 2015 (n = 1916). Clinical features and the severity of impairments were compared among three groups: children with current epilepsy (n = 604), those with resolved epilepsy by age 5 years (n = 109), and those without epilepsy (n = 1203). Additionally, a subset of the registry cohort attending Children's Hospital Westmead (n = 256) was analysed to compare epilepsy and treatment characteristics between drug-responsive (n = 83) and drug-resistant groups (n = 147) using logistic regression and hierarchical cluster analysis. RESULTS: Manual Ability Classification System levels IV and V, intellectual impairment, and vision impairment were found to be associated with epilepsy in children with CP on multivariable analysis (p < 0.01). Moderate to severe intellectual impairment and bilateral spastic CP were independent positive and negative predictors of epilepsy persistence at the age of 5 years respectively (p < 0.05). Microcephaly and multiple seizure types were predictors of drug-resistant epilepsy (area under the receiver operating characteristic curve of 0.83; 95% confidence interval 0.77-0.9). Children with a known genetic cause (14%) and CP epilepsy surgery group (4.3%) formed specific clinical subgroups in CP epilepsy. INTERPRETATION: Our study highlights important clinical associations of epilepsy, its resolution, and treatment response in children with CP, providing valuable knowledge to aid in counselling families and identifying distinct prognostic groups for effective medical surveillance and optimal treatment.

A natural history study of autosomal dominant GUCY2D-associated cone-rod dystrophy.

PURPOSE: To describe the natural history of autosomal dominant (AD) GUCY2D-associated cone-rod dystrophies (CRDs), and evaluate associated structural and functional biomarkers. METHODS: Retrospective analysis was conducted on 16 patients with AD GUCY2D-CRDs across two sites. Assessments included central macular thickness (CMT) and length of disruption to the ellipsoid zone (EZ) via optical coherence tomography (OCT), electroretinography (ERG) parameters, best corrected visual acuity (BCVA), and fundus autofluorescence (FAF). RESULTS: At first visit, with a mean age of 30 years (range 5-70 years), 12 patients had a BCVA below Australian driving standard (LogMAR ≥ 0.3 bilaterally), and 1 patient was legally blind (LogMAR ≥ 1). Longitudinal analysis demonstrated a deterioration of LogMAR by - 0.019 per year (p < 0.001). This accompanied a reduction in CMT of - 1.4 µm per year (p < 0.0001), lengthened EZ disruption by 42 µm per year (p = < 0.0001) and increased area of FAF by 0.05 mm2 per year (p = 0.027). Similarly, cone function decreased with increasing age, as demonstrated by decreasing b-wave amplitude of the light-adapted 30 Hz flicker and fused flicker (p = 0.005 and p = 0.018, respectively). Reduction in CMT and increased EZ disruption on OCT were associated with functional changes including poorer BCVA and decreased cone function on ERG. CONCLUSION: We have described the natural long-term decline in vision and cone function associated with mutations in GUCY2D and identified a set of functional and structural biomarkers that may be useful as outcome parameters for future therapeutic clinical trials.

Patterns of parental online health information-seeking behaviour.

AIM: This study aimed to understand parents' online health information-seeking behaviour and the potential influence of this on their relationship with their child's physician. METHODS: A survey regarding parental online health information-seeking behaviour was administered to parents of children aged under 18 years admitted to an Australian tertiary paediatric hospital, paediatric hospital ward and paediatric clinic, and in their social media networks. Responses were presented as frequencies and percentages. Associations between parents' trust in their child's doctor and survey responses were analysed using χ2 tests. RESULTS: In all, 300 surveys were completed. Most parents (89%) reported searching for online health information when their child was sick. Some (31%) followed online health information instead of going to the doctor. Parents who trusted their child's doctor were more likely to follow the doctor instead of online health information when it contained conflicting advice. Most parents (91%) wanted health-care professionals' help in searching for online health information. CONCLUSION: Almost all parents search for online health information, but most do not act on it. Parents' trust in their child's doctor influences how parents use online health information. Thus, clinicians could recommend trustworthy websites with information that complements their advice to ensure parents access reliable online health information.

Does pre-school developmental assessment agree with later intellectual assessment? A retrospective cohort study.

AIM: This study sought to assess the association between early developmental assessment of toddlers with idiopathic global developmental delay (GDD) and their later intelligence test scores. METHODS: Toddlers with idiopathic GDD attending a community clinic over a 6-year period were assessed initially using the Griffiths Mental Development Scales - Extended Revised version (GMDS-ER) and later completing formal intelligence testing using the Stanford-Binet Intelligence Scale - 5th Edition (SB5) at age 4-6 years. Spearman's correlation was used to assess the association of quotient scores across the tools. The composite quotient (GQ) and the subscale quotients of GMDS-ER were correlated with the full-scale IQ (FSIQ), verbal and non-verbal IQ scores from the SB5. RESULTS: Thirty of 153 children assessed at the clinic were eligible for the study. The correlation between GMDS-ER GQ and later SB5 FSIQ was strong (r = 0.86, P < 0.001). The subscales' associations were moderate to strong (0.48-0.71). Eighty-six percent (86%) of children with delay on GMDS-ER GQ were found later to be in the impaired category based on the FSIQ of the SB5. CONCLUSION: There was a strong association between toddlers' early developmental quotients and later IQ scores for children with idiopathic GDD, though agreement between early GDD diagnoses and later intellectual disability is not absolute. Individualised care is needed around prognostic advice and recommendations to caregivers and families in the early years, so they may effectively plan for interventions, supports and later reassessment to optimise their child's development and learning.

FGF21 outperforms GDF15 as a diagnostic biomarker of mitochondrial disease in children.

Several studies have shown serum fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) levels are elevated in patients with mitochondrial disease (MD) where myopathy is a feature. In this study we investigated the utility of FGF21 and GDF15 as biomarkers for MD in a phenotypically and genotypically diverse pediatric cohort with suspected MD against a panel of healthy controls and non-mitochondrial disease controls with some overlapping clinical features. Serum was collected from 56 children with MD, 104 children with non-mitochondrial disease (27 neuromuscular, 26 cardiac, 21 hepatic, 30 renal) and 30 pediatric controls. Serum FGF21 and GDF15 concentrations were measured using ELISA, and their ability to detect MD was determined. Median FGF21 and GDF15 serum concentrations were elevated 17-fold and 3-fold respectively in pediatric MD patients compared to the healthy control group. Non-mitochondrial disease controls had elevated serum GDF15 concentrations while FGF21 concentrations were in the normal range. Elevation of GDF15 in a range of non-mitochondrial pediatric disorders limits its use as a MD biomarker. FGF21 was elevated in MD patients with a spectrum of clinical phenotypes, including those without myopathy. Serum FGF21 had an area under the receiver operating characteristic curve of 0.87, indicating good ability to discriminate between pediatric MD and healthy and non-mitochondrial disease controls. Triaging of pediatric MD patients by clinical phenotyping and serum FGF21 testing, followed by massively parallel sequencing, may enable more rapid diagnosis of pediatric MD.

Maternal autoimmunity and inflammation are associated with childhood tics and obsessive-compulsive disorder: Transcriptomic data show common enriched innate immune pathways.

Although genetic variation is a major risk factor of neurodevelopmental disorders, environmental factors during pregnancy and early life are also important in disease expression. Animal models demonstrate that maternal inflammation causes fetal neuroinflammation and neurodevelopmental deficits, and brain transcriptomics of neurodevelopmental disorders in humans show upregulated differentially expressed genes are enriched in immune pathways. We prospectively recruited 200 sequentially referred children with tic disorders/obsessive-compulsive disorder (OCD), 100 autoimmune neurological controls, and 100 age-matched healthy controls. A structured interview captured the maternal and family history of autoimmune disease and other pro-inflammatory states. Maternal blood and published Tourette brain transcriptomes were analysed for overlapping enriched pathways. Mothers of children with tics/OCD had a higher rate of autoimmune disease compared with mothers of children with autoimmune neurological conditions (p = 0.054), and mothers of healthy controls (p = 0.0004). Autoimmunity was similarly elevated in first- and second-degree maternal relatives of children with tics/OCD (p < 0.0001 and p = 0.014 respectively). Other pro-inflammatory states were also more common in mothers of children with tics/OCD than controls (p < 0.0001). Upregulated differentially expressed genes in maternal autoimmune disease and Tourette brain transcriptomes were commonly enriched in innate immune processes. Pro-inflammatory states, including autoimmune disease, are more common in the mothers and families of children with tics/OCD. Exploratory transcriptome analysis indicates innate immune signalling may link maternal inflammation and childhood tics/OCD. Targeting inflammation may represent preventative strategies in pregnancy and treatment opportunities for children with neurodevelopmental disorders.

An exploration of factors associated with food protein-induced enterocolitis syndrome: Birth, infant feeding and food triggers.

BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergic disorder with a well-characterized phenotype, but limited understanding of factors associated with food cross-reactivity, severity and tolerance. METHODS: A retrospective cohort study spanning 20 years on children with acute FPIES from a single paediatric tertiary centre in New South Wales, Australia, focusing on identifying food trigger co-associations and factors associated with reaction severity, multiple trigger FPIES and/or tolerance was performed. RESULTS: A total of 168 individuals with 329 recorded FPIES episodes between 1997 and 2017 were included. 49% were male. The median age at first reaction was 5 months, and median age at diagnosis was 9 months. 73% experienced at least one severe FPIES reaction. Rice (45%), cow's milk (30%) and soya (13%) were the most common triggers. Rice or cow's milk FPIES was strongly associated with increased odds of having multiple trigger FPIES. The odds of having multiple food FPIES and severe reactions were slightly decreased with vaginal delivery. No factors were associated with increased risk of severe reactions. Infants with rice and grains FPIES outgrew their reactions at an earlier age, compared to those with fish FPIES. CONCLUSIONS: Rice remains the most common trigger in Australia with co-associations between rice/oats and cow's milk/soya observed. This suggests that taxonomically related foods may share similar protein structure and trigger similar mechanisms of antigen recognition. Vaginal delivery may have a mild protective effect on the development of multiple FPIES and severe reactions. No other features from birth or infant-feeding history influenced outcomes in FPIES.

Urinary incontinence during laughter in children: Is it giggle incontinence?

AIM: Giggle incontinence is a distinct entity of childhood daytime urinary incontinence (DUI), where children wet themselves only when they laugh. The prevalence of true giggle incontinence is unknown, with confusion about the diagnosis of urinary incontinence occurring during laughter and true giggle incontinence. The aim of the study is to improve our understanding of urinary incontinence during laughter by comparing those children with children who have DUI at other times, but not with laughter. METHODS: We conducted a retrospective medical record review of children with DUI who presented to a tertiary continence service from 2017 to 2018, collecting data on age, gender, associated comorbidities, lower urinary tract symptoms, investigations, provisional diagnosis at first visit and initial treatment responses. Differences between those with DUI occurring during laughter and those with DUI at other times, but not with laughter were compared using standard statistical methods. RESULTS: Of the 277 new patients seen during the study period, 140 (51%) had DUI, and of these, 72 (51%) had DUI occurring during laughter. Children with incontinence occurring during laughter were more likely to have incontinence associated with other activities. One child had giggle incontinence according to the International Children's Continence Society's definition. Four other children were referred specifically for urinary incontinence associated with laughter, with the term giggle incontinence sometimes used by the referring doctor. CONCLUSION: Children with DUI commonly experience incontinence during laughter, but true giggle incontinence is rare. Correct diagnosis is essential as it directs treatment.

Interventions for congenital talipes equinovarus (clubfoot).

BACKGROUND: Congenital talipes equinovarus (CTEV), also known as clubfoot, is a common congenital orthopaedic condition characterised by an excessively turned-in foot (equinovarus) and high medial longitudinal arch (cavus). If left untreated it can result in long-term disability, deformity and pain. Interventions can be conservative (such as splinting or stretching) or surgical. Different treatments might be effective at different stages: at birth (initial presentation); when initial treatment does not work (resistant presentation); when the initial treatment works but the clubfoot returns (relapse/recurrent presentation); and when there has been no early treatment (neglected presentation). This is an update of a review first published in 2010 and last updated in 2014. OBJECTIVES: To assess the effects of any intervention for any type of CTEV in people of any age. SEARCH METHODS: On 28 May 2019, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL Plus, AMED and Physiotherapy Evidence Database. We also searched for ongoing trials in the WHO International Clinical Trials Registry Platform and ClinicalTrials.gov (to May 2019). We checked the references of included studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs evaluating interventions for CTEV, including interventions compared to other interventions, sham intervention or no intervention. Participants were people of all ages with CTEV of either one or both feet. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the risks of bias in included trials and extracted the data. We contacted authors of included trials for missing information. We collected adverse event information from trials when it was available. When required we attempted to obtain individual patient data (IPD) from trial authors for re-analysis. If unit-of-analysis issues were present and IPD unavailable we did not report summary data, MAIN RESULTS: We identified 21 trials with 905 participants; seven trials were newly included for this update. Fourteen trials assessed initial cases of CTEV (560 participants), four trials assessed resistant cases (181 participants) and three trials assessed cases of unknown timing (153 participants). The use of different outcome measures prevented pooling of data for meta-analysis, even when interventions and participants were comparable. All trials displayed high or unclear risks of bias in three or more domains. Twenty trials provided data. Two trials reported on the primary outcome of function using a validated scale, but the data were not suitable for inclusion because of unit-of-analysis issues, as raw data were not available for re-analysis. We were able to analyse data on foot alignment (Pirani score), a secondary outcome, from three trials in participants at initial presentation. The Pirani score is a scale ranging from zero to six, where a higher score indicates a more severe foot. At initial presentation, one trial reported that the Ponseti technique significantly improved foot alignment compared to the Kite technique. After 10 weeks of serial casting, the average total Pirani score of the Ponseti group was 1.15 points lower than that of the Kite group (mean difference (MD) -1.15, 95% confidence interval (CI) -1.32 to -0.98; 60 feet; low-certainty evidence). A second trial found the Ponseti technique to be superior to a traditional technique, with mean total Pirani scores of the Ponseti participants 1.50 points lower than after serial casting and Achilles tenotomy (MD -1.50, 95% CI -2.28 to -0.72; 28 participants; very low-certainty evidence). One trial found evidence that there may be no difference between casting materials in the Ponseti technique, with semi-rigid fibreglass producing average total Pirani scores 0.46 points higher than plaster of Paris at the end of serial casting (95% CI -0.07 to 0.99; 30 participants; low-certainty evidence). We found no trials in relapsed or neglected cases of CTEV. A trial in which the type of presentation was not reported showed no evidence of a difference between an accelerated Ponseti and a standard Ponseti treatment in foot alignment. At the end of serial casting, the average total Pirani score in the accelerated group was 0.31 points higher than the standard group (95% CI -0.40 to 1.02; 40 participants; low-certainty evidence). No trial assessed gait using a validated assessment. Health-related quality of life was reported in some trials but data were not available for re-analysis. There is a lack of evidence for the addition of botulinum toxin A during the Ponseti technique, different types of major foot surgery or continuous passive motion treatment following major foot surgery. Most trials did not report on adverse events. Two trials found that further serial casting was more likely to correct relapse after Ponseti treatment than after the Kite technique, which more often required major surgery (risk differences 25% and 50%). In trials evaluating serial casting techniques, adverse events included cast slippage (needing replacement), plaster sores (pressure areas), and skin irritation. Adverse events following surgical procedures included infection and the need for skin grafting. AUTHORS' CONCLUSIONS: From the evidence available, the Ponseti technique may produce significantly better short-term foot alignment compared to the Kite technique. The certainty of evidence is too low for us to draw conclusions about the Ponseti technique compared to a traditional technique. An accelerated Ponseti technique may be as effective as a standard technique, but results are based on a single small comparative trial. When using the Ponseti technique semi-rigid fibreglass casting may be as effective as plaster of Paris. Relapse following the Kite technique more often led to major surgery compared to relapse following the Ponseti technique. We could draw no conclusions from other included trials because of the limited use of validated outcome measures and the unavailability of raw data. Future RCTs should address these issues.

The relationship between urinary incontinence and obesity in childhood.

AIM: To explore associations between weight and type/frequency of urinary incontinence (UI) in children presenting to a tertiary hospital incontinence clinic. METHODS: We retrospectively reviewed medical records of children who first attended the incontinence clinic at The Children's Hospital at Westmead between January 2004 and December 2014. A random sample of 1000 children was selected from 2022 patient records, and data were collected on weight, height, age, gender, UI parameters, bowel habits and medical history. Associations between predictors (weight categories, gender, snoring, constipation, faecal incontinence) and outcomes (daytime urinary incontinence (DUI) and nocturnal enuresis (NE)) were examined using χ2 tests and logistic regression analysis. RESULTS: A total of 862 children were included in the study; 54% were male, and 28% were overweight/obese. No evidence of difference was found between the underweight/normal and overweight/obese weight children with NE (34 vs. 39%), DUI (7 vs. 9%) or combined NE and DUI (58 vs. 52.1%), P = 0.23. The frequency of NE (83 vs. 82%, P = 0.56) and DUI (52 vs. 58%, P = 0.20) was similar between the weight groups. CONCLUSION: In a large cohort of children presenting to a tertiary incontinence clinic, weight was not associated with the type or frequency of UI.

Completeness of protocols for clinical trials in children submitted to ethics committees.

AIM: Studies of published clinical trials involving children have shown frequent omissions in key aspects of design and conduct, but these problems may be artefactual and due to editorial processes and space limitations. To determine actual design and conduct, we analysed the completeness of key domains in trial protocols involving children submitted to Human Research Ethics Committees. METHODS: The ethics committees of all eight children's hospitals in Australia were invited to participate. De-identified trial protocols submitted for review in 2012 were evaluated using a checklist derived from Consolidated Standards of Reporting Trials, the Cochrane Risk of Bias Tool and Good Clinical Practice guidelines. RESULTS: Four ethics committees agreed to participate, and 69 protocols were analysed. The domains almost always reported were clustered around the background and trial plan (planned interventions for each group (99%), specific objectives (97%) and scientific background (96%)). Risk-of-bias domains such as random sequence generation and blinding of participants were often reported (75-90%). Domains least reported were clustered around the statistical analysis plan (66%), specified intention-to-treat analysis (54%), the justification for the proposed trial based upon a systematic review (48%) and age-specific outcomes (48%). CONCLUSIONS: Protocols of trials involving children assessed by ethics committees generally include details on background and basic design, but many key domains in trial design and conduct are not covered. Despite widespread recognition of how problems in the design and conduct of trials may lead to unreliable results, investigators still appear to be omitting key elements in trial protocols.

Publishing trends in Journal of Paediatric Surgery, Pediatric Surgery International and European Journal of Pediatric Surgery over the past three decades.

The aim of this study was an analysis of the changing publication trends over the last three decades in the Journal of Pediatric Surgery (JPS), Pediatric Surgery International (PSI) and European Journal of Pediatric Surgery (EJPS) by studying the bibliometric variables, authorship, collaboration, and citation trends. A previously applied methodology using intermittent years was applied to review the archives of JPS, PSI and EJPS over the last 30 years. Citation data were collected from the Web of Science database. Statistical analysis was performed using SAS 9.4 software. A total of 1917 articles originating from 63 countries met the inclusion criteria. The number of articles published every year increased significantly in the last three decades from 336 in 1987 to 626 in 2017 (P < 0.0001). Multinational papers made up 5% of the total, of which 58% involved more than one continent. A majority of papers (75%) were single institution papers, there was strong evidence of an increase in multi-institution publications over time. There was a statistically significant increase in the number of female first and corresponding author. The publishing landscape of paediatric surgery has evolved to be more inclusive with increased collaboration, female authors and mentors and more publications from developing nations.

Outcomes after second surgery for recurrent glioblastoma: a retrospective case-control study.

Studies looking at the benefit of surgery at first relapse (second surgery) for recurrent glioblastoma were confounded by including patients with varying grades of glioma, performance status and extent of resection. This case-controlled study aims to remove these confounders to assess the survival impact of second surgery in recurrent glioblastoma. Retrospective data on patients with glioblastoma recurrence at two tertiary Australian hospitals from July 2009 to April 2015 was reviewed. Patients who had surgery at recurrence were matched with those who did not undergo surgery at recurrence, based on the extent of their initial resection and age. Overall survival (OS1 assessed from initial diagnosis and OS2 from the date of recurrence) as well as functional outcomes after resection were analysed. There were 120 patients (60 in each institution); median age at diagnosis was 56 years. Median OS1 was 14 months (95% CI 11.5-15.7) versus 22 months (95% CI 18-25) in patients who did not undergo second surgery and those with surgery at recurrence. OS2 was improved by second surgery (4.7 vs 9.6, HR 0.52, 95% CI 0.38-0.72, P < 0.001), and by chemotherapy, given at recurrence, (HR 0.47, 95% CI 0.24-0.92, P = 0.03). After second surgery, 80% did not require rehabilitation and 61% were independently mobile. Second surgery for recurrent glioblastoma was associated with a survival advantage. Chemotherapy independent of surgery, also improved survival. Functional outcomes were encouraging. More research is required in the era of improved surgical techniques and new antineoplastic therapies.

Determining parents' patterns of behaviour when searching for online information on their child's health.

AIM: The internet has enabled parents to become informed medical consumers and take an active role in their child's treatment. We aimed to determine parents' online medical information-seeking behaviour about their child's health. This included sources of information, reasons for searching, use and assessment of information and whether parents wanted assistance with searching and assessing information. METHODS: A questionnaire was distributed to 331 parents and carers of inpatients and outpatients at Children's Hospital at Westmead in 2015. Most questions involved tick-box responses and a few free-text responses. Responses were tabulated and described by frequencies and percentages. Associations between participant demographics and responses were examined using chi-square tests. RESULTS: In all, 308 (93%) questionnaires were returned. Most participants (90%) reported searching for medical information about their child's health. Of these, 96% searched the internet, and of these, 63% used a smartphone. The most common reason for searching before seeing the doctor was to prepare questions. The most common reasons for searching after seeing the doctor were to know more and because participants had more questions. Only half (57%) ascertained whether an information source was reliable. Most wanted guidance on searching (69%) and assessing reliability (77%). CONCLUSIONS: Almost all parents search for online information about their child's health, but most are unsure whether the information they find is trustworthy and are hesitant to act on or present it to their child's doctor. Health professionals could discuss this with parents during consultations to dispel potential misunderstandings and provide guidance on searching and assessing.

Allergic gastroenteritis hospital admission time trends in Australia and New Zealand.

AIM: Recent epidemiological studies indicate increases in hospital food allergy-related anaphylaxis admission rates in Australian and New Zealand. The aim of the study was to examine whether non-IgE-mediated food allergy might have increased in parallel. METHODS: We analysed childhood hospital admissions rates by ICD 10 codes for allergic gastroenteritis (AG) and infective gastroenteritis in Australia and New Zealand between June 1998 and July 2014. RESULTS: In Australia, most AG-related admissions (73%) occurred in those aged <1 year and increased by 7.3%/year (95% confidence interval (CI) 5.5-9.3, P < 0.0001) from 6.8 to 26.5/105 population. Similar trends were observed for New Zealand; 81% of admissions occurred in those aged <1 year and increased by 9.4%/year (95% CI 5.5-9.3, P < 0.0001) from 7.2 to 30.7/105 population. By contrast there were no significant changes in AG-related admission rates in the older patients and infective gastroenteritis admissions fell in both countries in those aged <1 year; Australia by 4.4%/year (95% CI 4.3-4.6, P < 0.0001) and in New Zealand by 5.8%/year (95% CI 5.4-6.2, P < 0.0001). CONCLUSION: We observed a fourfold increase in AG-related admission rates in two countries with known high rates of IgE-mediated food allergy/anaphylaxis. If confirmed by other studies, it will be of interest to determine if factors thought to contribute to the increase in IgE-mediated food allergy might also play a role in non-IgE-mediated gastroenterological food allergy syndromes.

Food protein-induced enterocolitis syndrome in Australia: A population-based study, 2012-2014.

BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated gastrointestinal allergic disorder. Large population-based FPIES studies are lacking. OBJECTIVE: We sought to determine the incidence and clinical characteristics of FPIES in Australian infants. METHODS: An Australia-wide survey (2012-2014) was undertaken through the Australian Paediatric Surveillance Unit, with monthly notification of new cases of acute FPIES in infants aged less than 24 months by 1400 participating pediatricians. RESULTS: Two hundred thirty infants with FPIES were identified. The incidence of FPIES in Australian infants (<24 months) was 15.4/100,000/y. Median age of first episode, diagnosis, and notification were 5, 7, and 10 months, respectively. There was no sex predilection. Seven percent of infants had siblings with a history of FPIES, and 5% reacted during exclusive breast-feeding. Sixty-eight had a single food trigger (20% had 2 and 12% had ≥3 food triggers). The most common FPIES triggers were rice (45%), cow's milk (33%), and egg (12%). Fifty-one percent of infants reacted on their first known exposure. Infants with FPIES to multiple versus single food groups were younger at the initial episode (4.6 vs 5.8 months [mean], P = .001) and more frequently had FPIES to fruits, vegetables, or both (66% vs 21%, P < .0001). Infants exclusively breast-fed for more than 4 months had a trend toward lower rates of FPIES to multiple food groups (23% vs 36%, P = .06). Sixty-four percent of infants with FPIES to multiple foods, which included cow's milk, had coassociated FPIES to solid foods. Forty-two percent of infants with FPIES to fish reacted to other food groups. CONCLUSIONS: FPIES is not rare, with an estimated incidence of 15.4/100,000/y. Rice is the most common food trigger in Australia. Factors associated with FPIES to multiple foods included early-onset disease and FPIES to fruits, vegetables, or both.

A randomized trial of egg introduction from 4 months of age in infants at risk for egg allergy.

BACKGROUND: Epidemiologic evidence suggests delayed introduction of egg might not protect against egg allergy in infants at risk of allergic disease. OBJECTIVE: We sought to assess whether dietary introduction of egg between 4 and 6 months in infants at risk of allergy would reduce sensitization to egg. METHODS: We conducted a randomized controlled trial in infants with at least 1 first-degree relative with allergic disease. Infants with a skin prick test (SPT) response to egg white (EW) of less than 2 mm were randomized at age 4 months to receive whole-egg powder or placebo (rice powder) until 8 months of age, with all other dietary egg excluded. Diets were liberalized at 8 months in both groups. The primary outcome was an EW SPT response of 3 mm or greater at age 12 months. RESULTS: Three hundred nineteen infants were randomized: 165 to egg and 154 to placebo. Fourteen infants reacted to egg within 1 week of introduction (despite an EW SPT response <2 mm at entry) and were unsuitable for intervention. Two hundred fifty-four (83%) infants were assessed at 12 months of age. Loss to follow-up was similar between groups. Sensitization to EW at 12 months was 20% and 11% in infants randomized to placebo and egg, respectively (odds ratio, 0.46; 95% CI, 0.22-0.95; P = .03, χ2 test). The absolute risk reduction was 9.8% (95% CI, 8.2% to 18.9%), with a number needed to treat of 11 (95% CI, 6-122). Levels of IgG4 to egg proteins and IgG4/IgE ratios were higher in those randomized to egg (P < .0001 for each) at 12 months. There was no effect on the proportion of children with probable egg allergy (placebo, 13; egg, 8). CONCLUSIONS: Introduction of whole-egg powder into the diets of high-risk infants reduced sensitization to EW and induced egg-specific IgG4 levels. However, 8.5% of infants randomized to egg were not amenable to this primary prevention.