Sydney Children Research Articles

Clinical characteristics and in-hospital outcomes associated with RSV-ALRI compared to other viral ALRI in hospitalised children under two years old.

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infections (ALRIs) associated hospitalisations in children. It is unclear if hospitalized RSV-ALRI differs in clinically from other viral ALRIs. We aimed to compare the disease impact of hospitalised RSV with other viral ALRI in children under 2 years. We conducted a retrospective study using electronic medical records of children under 2 hospitalized with ALRIs at Sydney Children's Hospitals Network from 2020-2022. We compared demographics and clinical features between RSV-positive and RSV-negative (positive for other viruses) cases. Poisson quasi-likelihood regression was used to estimate adjusted prevalence ratios (aPRs) for three in-hospital outcomes: length of stay, need for respiratory support and intensive care. We examined 330 children under 2 years hospitalized with RSV-positive ALRIs and 330 with RSV-negative ALRIs (positive for other viruses). RSV-positive cases were older (12 vs. 8 months, p<0.001) and more often presented with cough (99% vs. 92%), fever (80% vs. 58%), crackles (89% vs. 76%), hypoxia (50% vs. 36%), and lethargy (36% vs. 20%). They were also more likely to undergo chest x-rays (74% vs. 49%) and receive antibiotics (65% vs. 35%). Adjusted analysis showed RSV-positive children had a higher likelihood of LOS > 2 days (aPR 1.95, 95% CI 1.14-3.36).). However, there were no differences in the need for intensive care or respiratory support. Children with RSV-ALRI exhibited more severe symptoms, received more antibiotics, and had longer hospital stays compared to those with other viral ALRIs, underscoring the need for effective prevention and treatment strategies for RSV.

Travel-associated illness in children in pre-pandemic Western Sydney, 2018-2020.

Observational cohort study. In the 18 months immediately before the COVID-19 pandemic (2018-2020), we prospectively collected demographic, travel and clinical data from children with travel-acquired illness or injury identified by active surveillance of CHW Emergency Department attendees and referrals to the infectious diseases service. We identified 587 returned child travellers with an illness or injury associated with overseas travel. Most were aged younger than 5 (62.8%) and had travelled within the Asia-Pacific region (84.6%). The main reason for travel, where recorded (50.3%), was visiting friends and relatives (VFR)(65.4%). Most travellers (90.1%) had a common childhood infection, illness or injury coincidentally acquired during travel, including respiratory infection (37.5%), acute diarrhoea (15.7%) and nonspecific febrile illness (13.1%). Exotic/nonendemic infections were uncommon (9.9%, including potential rabies exposure) but were associated with much higher admission rates than 'cosmopolitan' (globally distributed) diseases (74.2% vs 21.9%). Most of these occurred in VFR travellers (86.3%); enteric fever, largely acquired in South Asia, predominated (51.7%). One in five admitted patients had a disease for which specific pretravel vaccination is available. Receipt of pretravel vaccines was infrequently recorded. Returned child travellers in Western Sydney frequently presented with respiratory infections and may be a key population for surveillance of imported respiratory viruses. The burden of exotic disease was small and borne by VFR travellers. Travel-related illness in Western Sydney could be reduced by health education of travellers and targeted pretravel vaccination, especially typhoid vaccination for VFR travellers to South Asia. Universal, systematic screening of emergency department attendees for recent overseas travel would improve surveillance of travel-related illness.

Parental perceptions and knowledge toward Asthma Action Plans

Introduction Personalized Asthma Action Plans (AAPs) are a cornerstone of pediatric asthma management. We aimed to assess parental knowledge and perceptions of the use of AAPs in managing their child’s asthma. Methods In 2023 we conducted a cross-sectional survey to assess knowledge and perceptions of AAPs in parents/caregivers of children aged 0–17 years with asthma who had an AAP and attended respiratory clinics at Sydney Children’s Hospital, Randwick. The questionnaire included parental perceptions on the utility of AAPs, parental asthma management self-efficacy (PAMSE), and an adapted version of the Asthma Action Plan Knowledge Interview tool (AAPKI). Descriptive statistics and regression analyses were used to assess associations between AAPKI, PAMSE and other outcomes. Results Seventy-one parents completed the survey. Mean PAMSE score was 4.2/5 (SD 0.5). Median AAPKI score was 70.2% out of 100% (IQR 20.4%). Most parents (80.0%, n = 56) were satisfied/very satisfied with using AAPs to manage their child’s asthma. Most agreed/strongly agreed that AAPs were helpful in knowing when to seek medical attention for their child’s asthma (81.7%, n = 58), helped their understanding of asthma severity (81.7%, n = 58), and increased their confidence in asthma management (76.0%, n = 54). Over half of parents (55.7%, n = 39) would prefer AAPs digitally and majority (78.6%, n = 55) would like color-coded AAPs. Conclusion High levels of AAP knowledge and self-efficacy scores were demonstrated. Most parents expressed understanding of the benefits of AAPs. Our findings suggest parents of children with asthma prefer AAPs in color and in digital version which may help guide standardization of AAPs across Australia.

Evaluation of telehealth in delivering diagnostic developmental assessments for children in South Western Sydney during the COVID-19 pandemic: Clinician and family perspectives.

Children with neuro-developmental disorders faced significant challenges in accessing services during the COVID-19 pandemic. Telehealth has been adopted by health services globally to facilitate access to clinical services. Our aims were to evaluate the utility of the telehealth modality for providing developmental assessment services and explore enablers and barriers to using telehealth, in a culturally diverse and socioeconomically disadvantaged population in Sydney. We reviewed telehealth developmental assessments in South Western Sydney conducted between 1 April and 30 June 2020. Data were collated on demographics; telehealth modality; diagnostic formulation; recommendations; and requested follow up. We conducted retrospective semi-structured telephone interviews with 79 families and 11 clinicians about their telehealth experience. Thematic analysis was carried out on the open text responses. Of 205 children assessed across six sites, median age was 48 months; 45% were assessed with video and 55% with telephone only. Diagnostic formulation and therapeutic recommendations were provided for 203 (99%) children and 138 (67%) were asked to come for face-to-face follow-up. The majority of families (76%) were satisfied or extremely satisfied with telehealth. Median clinician satisfaction was 3.5 out of 5, whilst clinician confidence with diagnostic formulation was 4 out of 5. Qualitative data revealed a range of barriers and enablers. Telehealth was a successful modality for contributing to the assessment journey for children with neuro-developmental disorders in our culturally, linguistically and socioeconomically diverse clinical population in the context of a pandemic lockdown. We discuss the potential for telehealth modalities in child developmental assessments beyond the pandemic.

Patient and carer transition outcomes and experiences at the Westmead Centre for Adolescent and Young Adult Health, Westmead, Australia: protocol for a longitudinal cohort study

IntroductionThe Westmead Centre for Adolescent and Young Adult Health is a purpose-built facility supporting integrated care for young patients with a variety of long-term health conditions transitioning from paediatric services...

EPIC-CP pilot trial study protocol: a multicentre, randomised controlled trial investigating the feasibility and acceptability of social prescribing for Australian children with cerebral palsy

IntroductionThe social determinants of health contribute to poorer health outcomes for children with cerebral palsy (CP) and are barriers to families accessing health services. At an individual level, social determinants...

Ketogenic diet modifies ribosomal protein dysregulation in KMT2D Kabuki syndrome

BackgroundKabuki syndrome (KS) is a genetic disorder caused by DNA mutations in KMT2D, a lysine methyltransferase that methylates histones and other proteins, and therefore modifies chromatin structure and subsequent gene expression. Ketones, derived from the ketogenic diet, are histone deacetylase inhibitors that can ‘open’ chromatin and encourage gene expression. Preclinical studies have shown that the ketogenic diet rescues hippocampal memory neurogenesis in mice with KS via the epigenetic effects of ketones. MethodsSingle-cell RNA sequencing and mass spectrometry-based proteomics were used to explore molecular mechanisms of disease in individuals with KS (n=4) versus controls (n=4). FindingsPathway enrichment analysis indicated that loss of function mutations in KMT2D are associated with ribosomal protein dysregulation at an RNA and protein level in individuals with KS (FDR <0.05). Cellular proteomics also identified immune dysregulation and increased abundance of other lysine modification and histone binding proteins, representing a potential compensatory mechanism. A 12-year-old boy with KS, suffering from recurrent episodes of cognitive decline, exhibited improved cognitive function and neuropsychological assessment performance after 12 months on the ketogenic diet, with concomitant improvement in transcriptomic ribosomal protein dysregulation. InterpretationOur data reveals that lysine methyltransferase deficiency is associated with ribosomal protein dysfunction, with secondary immune dysregulation. Diet and the production of bioactive molecules such as ketone bodies serve as a significant environmental factor that can induce epigenetic changes and improve clinical outcomes. Integrating transcriptomic, proteomic, and clinical data can define mechanisms of disease and treatment effects in individuals with neurodevelopmental disorders. FundingThis study was supported by the Dale NHMRC Investigator Grant (APP1193648) (R.D), Petre Foundation (R.D), and The Sydney Children’s Hospital Foundation/Kids Research Early and Mid-Career Researcher Grant (E.T).

'High hopes for treatment': Australian stakeholder perspectives of the clinical translation of advanced neurotherapeutics for rare neurological diseases.

Advanced therapies offer unprecedented opportunities for treating rare neurological disorders (RNDs) in children. However, health literacy, perceptions and understanding of novel therapies need elucidation across the RND community. This study explored healthcare professionals' and carers' perspectives of advanced therapies in childhood-onset RNDs. In this mixed-methodology cross-sectional study, 20 healthcare professionals (clinicians, genetic counsellors and scientists) and 20 carers completed qualitative semistructured interviews and custom-designed surveys. Carers undertook validated psychosocial questionnaires. Thematic and quantitative data analysis followed. Participants described high positive interest in advanced therapies, but low knowledge of, and access to, reliable information. The substantial 'therapeutic gap' and 'therapeutic odyssey' common to RNDs were recognised in five key themes: (i) unmet need and urgency for access; (ii) seeking information; (iii) access, equity and sustainability; (iv) a multidisciplinary and integrated approach to care and supportand (v) difficult decision-making. Participants were motivated to intensify RND clinical trial activity and access to advanced therapies; however, concerns around informed consent, first-in-human trials and clinical trial procedures were evident. There was high-risk tolerance despite substantial uncertainties and knowledge gaps. RNDs with high mortality, increased functional burdens and no alternative therapies were consistently prioritised for the development of advanced therapies. However, little consensus existed on prioritisation to treatment access. This study highlights the need to increase clinician and health system readiness for the clinical translation of advanced therapeutics for RNDs. Co-development and use of educational and psychosocial resources to support clinical decision-making, set therapeutic expectations and promotion of equitable, effective and safe delivery of advanced therapies are essential. Participant insights into the psychosocial burden and information needto enhance the delivery of care in this formative study are informing ongoing partnerships with families, including co-production and dissemination of psychoeducational resources featuring their voices hosted on the Sydney Children's Hospitals Network website SCHNBrain-AidResources.

Genomic multidisciplinary teams: A model for navigating genetic mainstreaming and precision medicine.

Recent rapid advances in genomics are revolutionising patient diagnosis and management of genetic conditions. However, this has led to many challenges in service provision, education and upskilling requirements for non-genetics health-care professionals and remuneration for genomic testing. In Australia, Medicare funding with a Paediatric genomic testing item for patients with intellectual disability or syndromic features has attempted to address this latter issue. The Sydney Children's Hospitals Network - Westmead (SCHN-W) Clinical Genetics Department established Paediatric and Neurology genomic multidisciplinary team (MDT) meetings to address the Medicare-specified requirement for discussion with clinical genetics, and increasing genomic testing advice requests. This SCHN-W genomic MDT was evaluated with two implementation science frameworks - the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) and GMIR - Genomic Medicine Integrative Research frameworks. Data from June 2020 to July 2022 were synthesised and evaluated, as well as process mapping of the MDT service. A total of 205 patients were discussed in 34 MDT meetings, facilitating 148 genomic tests, of which 73 were Medicare eligible. This was equivalent to 26% of SCHN-W genetics outpatient activity, and 13% of all Medicare-funded paediatric genomic testing in NSW. 39% of patients received a genetic diagnosis. The genomic MDT facilitated increased genomic testing at a tertiary paediatric centre and is an effective model for mainstreaming and facilitating precision medicine. However, significant implementation issues were identified including cost and sustainability, as well as the high level of resourcing that will be required to scale up this approach to other areas of medicine.

'Integrating Ethics and Equity with Economics and Effectiveness for newborn screening in the genomic age: A qualitative study protocol of stakeholder perspectives.

Newborn bloodspot screening is a well-established population health initiative that detects serious, childhood-onset, treatable conditions to improve health outcomes. With genomic technologies advancing rapidly, many countries are actively discussing the introduction of genomic assays into newborn screening programs. While adding genomic testing to Australia's newborn screening program could improve outcomes for infants and families, it must be considered against potential harms, ethical, legal, equity and social implications, and economic and health system impacts. We must ask not only 'can' we use genomics to screen newborns?' but 'should we'?' and 'how much should health systems invest in genomic newborn screening?'. This study will use qualitative methods to explore understanding, priorities, concerns and expectations of genomic newborn screening among parents/carers, health professionals/scientists, and health policy makers across Australia. In-depth, semi-structured interviews will be held with 30-40 parents/carers recruited via hospital and community settings, 15-20 health professionals/scientists, and 10-15 health policy makers. Data will be analysed using inductive content analysis. The Sydney Children's Hospital Network Human Research Ethics Committee approved this study protocol [2023/ETH02371]. The Standards for Reporting Qualitative Research will guide study planning, conduct and reporting. Few studies have engaged a diverse range of stakeholders to explore the implications of genomics in newborn screening in a culturally and genetically diverse population, nor in a health system underpinned by universal health care. As the first study within a multi-part research program, findings will be used to generate new knowledge on the risks and benefits and importance of ethical, legal, social and equity implications of genomic newborn screening from the perspective of key stakeholders. As such it will be the foundation on which child and family centered criteria can be developed to inform health technology assessments and drive efficient and effective policy decision-making on the implementation of genomics in newborn screening.

Abstract 3636: Myeloid cell rebound associated with GD2-CAR-T cell therapy in solid tumor patients

Abstract GD2 is a validated cancer immunotherapy target with highly restricted normal tissue expression. Promising activity of GD2-CAR-T cell therapy in diffuse midline glioma and neuroblastoma has promoted interest in this therapy. We initiated three phase 1 clinical trials of escalating doses of intravenously administered autologous GD2-CAR-T cells in patients with advanced GD2-positive solid tumors. Emerging evidence suggests that CAR-T cells may increase circulating myeloid derived suppressor cells (MDSCs) and that this event may be mediated and/or triggered by CAR-T cell-derived cytokines and chemokines. These findings may help to explain the limited persistence of CAR-T cell therapy in solid tumor patients. Hence, we sought evidence of MDSC generation and secretion of relevant cytokines and chemokines in our clinical trial patients. The CARPETS trial (www.anzctr.org.au: ACTRN12620000622909) recently closed to recruitment after enrolling 12 patients (7 melanoma, 4 colorectal cancer, and 1 sarcoma). No significant adverse events were attributable to CAR-T cell therapy. We opened two other GD2-CAR-T cell therapy trials in 2023: LEVI’S-CATCH (ACTRN12622000675729) in patients with diffuse midline glioma at Sydney Children’s Hospital and KARPOS (ACTRN12622001514796) in adult patients with recurrent glioblastoma at Royal Adelaide Hospital. To date, 3 patients have enrolled to LEVI’S-CATCH with the first patient clearing the dose limiting (DLT) evaluation period. Three patients completed enrolment to the first dose cohort of KARPOS without DLTs. In all CARPETS patients, CAR-T cell expansion, which was measured by by DNA quantitative PCR and flow cytometry, peaked during the 6-week post-CAR-T infusion DLT evaluation period. In 6 CARPETS patients for whom peripheral blood samples were available, we found by flow cytometry, newly formed or increased size of pre-existing subpopulations of non-classical monocytes and/or MDSCs of mononuclear and/or polymorphonuclear class, which peaked at or after the time of peak CAR-T cell expansion. Typically, serum levels of inflammatory cytokines and chemokines such as TNF, IL-6, IL-8, CCL2, GM-CSF, and CXCL10, were detected only after the CAR-T cell infusion with variable patterns of the timing and concentration of analyte observed among the 12 patients. At the time of writing, blood samples from the first KARPOS patient showed CAR-T cell expansion and the subsequent increases in circulating myeloid derived suppressor cells and inflammatory cytokines. We expect that full data sets for these parameters will be presented for current and future enrolled patients to both studies. To improve CAR-T cell persistence in solid tumor patients, these data indicate the need for new therapeutic strategies to mitigate effects of CAR-T cell induced myeloid cells with antitumor activity. Citation Format: Michael P. Brown, Tessa Gargett, Nga T. Truong, Orazio Vittorio, David S. Ziegler. Myeloid cell rebound associated with GD2-CAR-T cell therapy in solid tumor patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3636.

Proton pump inhibitors, antibiotics, and atopy increase the risk of eosinophilic esophagitis in children with esophageal atresia.

To determine whether proton pump inhibitor (PPI)exposure is associated with an increased risk of developing eosinophilic esophagitis (EoE) in children with esophageal atresia (EA). A retrospective chart review of children with EA from January 1, 2005 to December31, 2020 was undertaken at Sydney Children's Hospital Randwick. Children with EA and EoE (cases) were matched (1:2) to children with only EA (controls) to compare PPI exposure. Other early-life factors such as infantile antibiotic exposure and personal or family history of atopy were also analyzed using simple and multivariable logistic regression. Of 184 children with EA, 46 (25%) developed EoE during this period. Thirty-eight EoE participants were matched to 76 controls. Children with EoE and EA received PPI for significantly higher durations (p = .018) and at significantly higher cumulative doses (p = .017) than controls. Food allergy (adjusted odds ratio [aOR],7.317; 95% confidence interval [CI],2.244-23.742), family history of atopy (aOR,3.504; 95% CI, 1.268-9.682), and infantile antibiotic exposure (aOR,1.040; 95% CI, 1.006-1.075) were also significantly associated with an increased risk of developing EoE in the EA cohort. Prolonged duration and high cumulative dose of PPI exposure were significantly associated with subsequent EoE development in children with EA. Food allergy, family history of atopy, and infantile antibiotic exposure in EA were also significantly associated with an increased risk of EoE development.

Reduction of Urinary Tract Infection in Pediatric Surgical Patients Using NSQIP-P and Quality Improvement Methodology.

Hospital-acquired urinary tract infections (UTIs) have a detrimental effect on patients, families, and hospital resources. The Sydney Children's Hospital Network (SCHN) participates in the NSQIP-Pediatric (NSQIP-P) to monitor postoperative complications. NSQIP-P data revealed that the median UTI rate at SCHN was 1.75% in 2019, 3.5 times higher than the NSQIP-P target rate of 0.5%. Over three quarters of the NSQIP-P identified patients with UTI also had a urinary catheterization performed intraoperatively. A quality improvement project was conducted between mid-2018 and 2021 to minimize catheter-associated UTIs (CAUTIs) at SCHN. NSQIP-P samples include pediatric (younger than 18 years) surgical patients from an 8-day cycle operative log. NSQIP-P data are statistically analyzed by the American College of Surgeons and provide biannual internationally benchmarked reports. The project used clinical redesign methodology with a 6-phase process for quality improvement projects. The objectives of the project were to reduce urinary catheter duration of use, educate parents or carers, and improve catheter care and insertion technique by health staff. The duration of a urinary catheter in situ reduced from a median of 4.5 to 3 days from 2017 to 2021. The median NSQIP-P UTI rate at SCHN was reduced by 47.4% from 1.75% in 2019 to 0.9% in 2022. A multifactorial approach in quality improvement has been shown to be an effective strategy to reduce UTI rates at SCHN, and patient outcomes were improved within a 3-year timeframe. Although this project has reduced UTI rates at SCHN, there remain opportunities for further improvement.

Seroprevalence of Japanese encephalitis virus-specific antibodies in Australia following novel epidemic spread: protocol for a national cross-sectional study

IntroductionJapanese encephalitis virus (JEV) is a mosquito-borne flavivirus that causes encephalitis and other morbidity in Southeast Asia. Since February 2022, geographically dispersed JEV human, animal and vector detections occurred on...

Digital psychosocial assessment of youth in Australian hospitals: From aspiration to implementation

Abstract Background Some of the leading causes of morbidity and mortality for Australian youth arise from modifiable psychosocial concerns. Psychosocial assessment can help identify young people at risk and support actions that protect wellbeing. The gold standard assessment for youth is the HEEADSSS interview. Australian governments recommend the HEEADSSS interview for young people in health settings, but adoption is still in its early stages. Recently, a digital self-assessment version of the HEEADSSS (the e-HEEADSSS) was piloted at the Sydney Children's Hospital Network. A program of research has been established to evaluate outcomes and consider broader implementation. Methods Study 1 involved a retrospective analysis to compare the HEEADSSS interview and the e-HEEADSSS. Documentation from 146 matched records collected at the Sydney Children's Hospital Network were analysed to compare approaches. Study 2 utilised a qualitative design to evaluate patient and staff barriers and facilitators to implementation and scale-up of the e-HEEADSSS. Patients (n = 8) and staff (n = 8) participated in online semi-structured interviews. Results Study 1 found the e-HEEADSSS improves assessment uptake and sensitivity compared to face-to-face interviews and takes less time. Disclosure rates were higher for all psychosocial categories especially in sensitive areas of emotions, drug use, sex, and safety. Study 2 found strong support for the e-HEEADSSS from patients and staff. Key benefits included design, functionality, reduced time, convenience, improved disclosure, perceived privacy, improved fidelity, and reduced stigma. Key challenges were available resources, continuity of staff training, clinical pathways, and risks of off-site completions. Conclusions The e-HEEADSSS shows promise as a psychosocial screening tool to support intervention for young people. More work is required to appropriately scale and sustain implementation of the e-HEEADSSS within the Australian health system. Key messages • Digital psychosocial assessments show promise for supporting the mental and physical health of adolescents and young adults. • Implementation of digital psychosocial assessments within the Australian health system requires considered support.

Asthma and Susceptibility to COVID-19 in Australian Children During Alpha, Delta and Omicron Waves of the COVID-19 Pandemic.

Earlier coronavirus-19 (COVID-19) pandemic reports did not implicate increased disease burden in asthmatics while subsequent findings have been inconsistent. To date, the impact of COVID-19 on childhood asthma remains undetermined and is further complicated with ongoing emergence of new variants. This study aimed to investigate association between asthma and COVID-19 for children in New South Wales (NSW), Australia and compare its differences across four major outbreaks from alpha, delta and omicron variants/subvariants. This is a retrospective cross-sectional study of all children aged ≤17 years old who sought care for COVID-19 at Sydney Children's Hospitals Network (SCHN) between 1 January 2020 and 31 May 2022. Of the 18,932 children with polymerase chain reaction (PCR) confirmed COVID-19 who attended SCHN, 60% received their care during delta wave, and 5.41% (n = 913) had prior diagnosis of asthma. Among children with COVID-19, the odds of having asthma were lower during alpha (aOR = 0.43; 95% CI, 0.19-0.83) and delta wave (aOR = 0.84; 95% CI, 0.73-0.96), but were higher during omicron wave (aOR = 1.56; 95% CI, 1.23-1.95). Length of hospital stay (LOS) for asthmatic children were increased by 0.55 days and 1.17 days during delta and the second omicron wave, respectively. Intensive care and mechanical ventilation requirements were not significantly different between asthmatic and non-asthmatic children. Eleven deaths were reported but none had asthma. Although children with asthma were more susceptible to COVID-19 infections during omicron waves compared to that of alpha or delta waves, they were not at greater risk of COVID-19 severity at any stage of the outbreak regardless of the predominant SARS-CoV-2 variants/subvariants.

Genotyping in patients with congenital adrenal hyperplasia by sequencing of newborn bloodspot samples.

Genotype-phenotype correlation in congenital adrenal hyperplasia (CAH) caused by 21-hydroxylase deficiency ranges from 45 to 97 %. We performed massively parallel sequencing of CYP21A2 on stored newborn bloodspot samples to catalogue the genotypes present in our patients with CAH and enable genotype-phenotype comparison. Participants≤15 years old with clinically diagnosed CAH were recruited from The Sydney Children's Hospitals Network. Phenotype was classified from clinical and biochemical details in the medical record as salt wasting (SW), simple virilising (SV), non-classic (NC) or an intermediate phenotype (SW/SV; SV/NC). Amplicon-based sequencing for CYP21A2 was performed on stored newborn bloodspot samples by the New South Wales Newborn Bloodspot Screening Laboratory on MiSeq™Dx (Illumina, California). Available genetic test results were also obtained from the medical records. Samples from 67 participants (43 % female, age 0.3-15 years) were sequenced, including 9 sibships. SW phenotype was present in 33/67 participants (49 %), SV in 9 (13 %) and NC in 16 (24 %). Intermediate phenotypes included SW/SV in seven participants (10 %) and SV/NC in two (3 %). Variants were identified in 90/116 alleles (78 %). A complete genotype was available in 47/67 participants (70 %). The most common genotype was homozygous c.293-13A/C>G (I2G) in 7/47 participants (15 %). Genotype correlated with the mostcommonly reported phenotype in 36/44 cases (82 %). Correlation was higher in SW and NC phenotypes. This study uses genetic testing of newborn bloodspots to identify and characterise the genotypes present in an ethnically diverse Australian population with CAH. It further strengthens our knowledge of genotype-phenotype correlations in CAH.

The Carrier Frequency of Two SMN1 Genes in Parents of Symptomatic Children with SMA and the Significance of SMN1 Exon 8 in Carriers.

Current carrier screening methods do not identify a proportion of carriers that may have children affected by spinal muscular atrophy (SMA). Additional genetic data is essential to inform accurate risk assessment and genetic counselling of SMA carriers. This study aims to quantify the various genotypes among parents of children with SMA. A retrospective cohort study was undertaken at Sydney Children's Hospital Network, the major SMA referral centre for New South Wales, Australia. Participants included children with genetically confirmed SMA born between 2005 and 2021. Data was collected on parent genotype inclusive of copy number of SMN1 exons 7 and 8. The number of SMN2 exon 7 copies were recorded for the affected children. Descriptive statistics were used to determine the proportion of carriers of 2+0 genotype classified as silent carriers. Chi-square test was used to correlate the association between parents with a heterozygous SMN1 exon 7 deletion and two copies of exon 8 and ≥3 SMN2 copy number in the proband. SMA carrier testing was performed in 118/154 (76.6%) parents, incorporating 59 probands with homozygous SMN1 deletions and one proband with compound heterozygote pathogenic variants. Among parents with a child with SMA, 7.6% had two copies of SMN1 exon 7. When only probands with a homozygous SMN1 exon 7 deletion were included, 6.9% of parents had two copies of SMN1 exon 7. An association was observed between heterozygous deletion of SMN1 exon 7 with two copies of exon 8 in a parent and ≥3 SMN2 copy number in the affected proband (p = 0.07). This study confirmed a small but substantial proportion of silent carriers not identified by conventional screening within an Australian context. Accordingly, the effectiveness of carrier screening for SMA is linked with genetic counselling to enable health literacy regarding high and low risk results and is complemented by new-born screening and maintaining clinical awareness for SMA. Gene conversion events may underpin the associations between parent carrier status and proband SMN2 copy number.

Psychosocial assessment of adolescents and young adults in paediatric hospital settings: patient and staff perspectives on implementation of the e-HEEADSSS

BackgroundThe main causes of morbidity and mortality for adolescents and young adults are preventable and stem from psychosocial and behavioural concerns. Psychosocial assessments can help clinicians to identify and respond holistically to risks and strengths that may impact upon a young person’s physical and mental health. Despite broad support at a policy level, the implementation of routine psychosocial screening for young people remains varied in Australian health settings. The current study focused on the pilot implementation of a digital patient-completed psychosocial assessment (the e-HEEADSSS) at the Sydney Children’s Hospital Network. The aim of this research was to evaluate patient and staff barriers and facilitators to local implementation.MethodsThe research used a qualitative descriptive research design. Semi-structured interviews were conducted online with 8 young patients and 8 staff members who had completed or actioned an e-HEEADSSS assessment within the prior 5 weeks. Qualitative coding of interview transcripts was carried out in NVivo 12. The Consolidated Framework for Implementation Research guided the interview framework and qualitative analyses.ResultsResults demonstrated strong support for the e-HEEADSSS from patients and staff. Key reported facilitators included strong design and functionality, reduced time requirements, greater convenience, improved disclosure, adaptability across settings, greater perceived privacy, improved fidelity, and reduced stigma for young people. The key barriers were related to concerns over available resources, the sustainability and continuity of staff training, perceived availability of clinical pathways for follow-up and referrals, and risks related to off-site completions. Clinicians need to adequately explain the e-HEEADSSS assessment to patients, educate them about it, and make sure that they receive timely feedback on the results. Greater reassurance and education regarding the rigour of confidentiality and data handling procedures is required for patients and staff.ConclusionsOur findings indicate that continued work is required to support the integration and sustainability of digital psychosocial assessments for young people at the Sydney Children’s Hospital Network. The e-HEEADSSS shows promise as an implementable intervention to achieve this goal. Further research is required to determine the scalability of this intervention across the broader health system.

National surveillance of severe microcephaly in Australia.

Acta PaediatricaAccepted Articles BRIEF REPORT National surveillance of severe microcephaly in Australia Carlos Nunez, Corresponding Author Carlos Nunez [email protected] orcid.org/0000-0002-5417-9582 The University of Sydney. Faculty of Medicine and Health, Discipline of Child and Adolescent Health, Sydney, NSW, Australia The Australian Paediatric Surveillance Unit (APSU). Sydney, NSW, Australia Correspondence Dr Carlos Nunez, the Australian Paediatric Surveillance (APSU), Level 2, Kids Research, The Children's Hospital at Westmead, Locked Bag 4001, Westmead NSW 2145, Australia. Email: [email protected]Search for more papers by this authorAnne Morris, Anne Morris The University of Sydney. Faculty of Medicine and Health, Discipline of Child and Adolescent Health, Sydney, NSW, Australia The Australian Paediatric Surveillance Unit (APSU). Sydney, NSW, Australia Kids Research, The Sydney Children's Hospitals Network (Westmead), Sydney, NSW, AustraliaSearch for more papers by this authorElizabeth J. Elliott, Elizabeth J. Elliott The University of Sydney. Faculty of Medicine and Health, Discipline of Child and Adolescent Health, Sydney, NSW, Australia The Australian Paediatric Surveillance Unit (APSU). Sydney, NSW, Australia Kids Research, The Sydney Children's Hospitals Network (Westmead), Sydney, NSW, AustraliaSearch for more papers by this author Carlos Nunez, Corresponding Author Carlos Nunez [email protected] orcid.org/0000-0002-5417-9582 The University of Sydney. Faculty of Medicine and Health, Discipline of Child and Adolescent Health, Sydney, NSW, Australia The Australian Paediatric Surveillance Unit (APSU). Sydney, NSW, Australia Correspondence Dr Carlos Nunez, the Australian Paediatric Surveillance (APSU), Level 2, Kids Research, The Children's Hospital at Westmead, Locked Bag 4001, Westmead NSW 2145, Australia. Email: [email protected]Search for more papers by this authorAnne Morris, Anne Morris The University of Sydney. Faculty of Medicine and Health, Discipline of Child and Adolescent Health, Sydney, NSW, Australia The Australian Paediatric Surveillance Unit (APSU). Sydney, NSW, Australia Kids Research, The Sydney Children's Hospitals Network (Westmead), Sydney, NSW, AustraliaSearch for more papers by this authorElizabeth J. Elliott, Elizabeth J. Elliott The University of Sydney. Faculty of Medicine and Health, Discipline of Child and Adolescent Health, Sydney, NSW, Australia The Australian Paediatric Surveillance Unit (APSU). Sydney, NSW, Australia Kids Research, The Sydney Children's Hospitals Network (Westmead), Sydney, NSW, AustraliaSearch for more papers by this author First published: 14 May 2023 https://doi.org/10.1111/apa.16846 This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi:10.1111/apa.16846. AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Accepted ArticlesAccepted, unedited articles published online and citable. The final edited and typeset version of record will appear in the future. RelatedInformation