Paediatrics (RCH) - Research Publications

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The characteristics of SARS-CoV-2-positive children in Australian hospitals: a PREDICT network study.

Ibrahim, L ; Wilson, C ; Tham, D ; Corden, M ; Jani, S ; Zhang, M ; Kochar, A ; Tan, KF ; George, S ; Phillips, NT ; Buntine, P ; Robins-Browne, K ; Chong, V ; Georgeson, T ; Lithgow, A ; Davidson, S ; O'Brien, S ; Tran, V ; Babl, FE (Wiley, 2023-06-05)

OBJECTIVES: To examine the clinical characteristics and short term outcomes for children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections who presented to Australian hospitals during 2020 and 2021. DESIGN, SETTING: Retrospective case review study in nineteen hospitals of the Paediatric Research in Emergency Departments International Collaborative (PREDICT) network from all Australian states and territories, including seven major paediatric tertiary centres and eight Victorian hospitals. PARTICIPANTS: SARS-CoV-2-positive people under 18 years of age who attended emergency departments or were admitted to hospital during 1 February 2020 - 31 December 2021. MAIN OUTCOME MEASURES: Epidemiological and clinical characteristics, by hospital care type (emergency department [ED] or inpatient care). RESULTS: A total of 1193 SARS-CoV-2-positive children and adolescents (527 girls, 44%) attended the participating hospitals (107 in 2020, 1086 in 2021). Their median age was 3.8 years (interquartile range [IQR], 0.8-11.4 years); 63 were Aboriginal or Torres Strait Islander people (5%). Other medical conditions were recorded for 293 children (25%), including asthma (86, 7%) and premature birth (68, 6%). Medical interventions were not required during 795 of 1181 ED presentations (67%); children were discharged directly home in 764 cases (65%) and admitted to hospital in 282 (24%; sixteen to intensive care units). The 384 admissions to hospital (including 102 direct admissions) of 341 children (25 infants under one month of age) included 23 to intensive care (6%); the median length of stay was three days (IQR, 1-9 days). Medical interventions were not required during 261 admissions (68%); 44 children received respiratory support (11%) and 21 COVID-19-specific treatments, including antiviral and biologic agents (5%). Being under three months of age (v one year to less than six years: odds ratio [OR], 2.6; 95% confidence interval [CI], 1.7-4.0) and pre-existing medical conditions (OR, 2.5; 95% CI, 1.9-3.2) were the major predictors of hospital admission. Two children died, including one without a known pre-existing medical condition. CONCLUSION: During 2020 and 2021, most SARS-CoV-2-positive children and adolescents who presented to participating hospitals could be managed as outpatients. Outcomes were generally good, including for those admitted to hospital.
Pre-Vaccination Human Papillomavirus Genotypes and HPV16 Variants among Women Aged 25 Years or Less with Cervical Cancer

Jayasinghe, YN ; Tabrizi, S ; Stevens, M ; Leong, TY-M ; Pyman, JR ; Grover, SM ; Garland, S (MDPI, 2023-03-01)

BACKGROUND: In 2007, Australia introduced a national human papillomavirus (HPV) vaccination program. In 2017, the onset of cervical screening changed from 18 to 25 years of age, utilising human papillomavirus (HPV) nucleic acid testing. The objective of the study is to describe the HPV genotypes and HPV16 variants in biopsies from women ≤ 25 years of age with cervical carcinoma (CC) (cases), compared with those aged >25 years (controls), in a pre-vaccination cohort. METHODS: HPV genotyping of archival paraffin blocks (n = 96) was performed using the INNO-LiPA HPV Genotyping assay. HPV16-positive samples were analysed for variants by type-specific PCR spanning L1, E2 and E6 regions. RESULTS: HPV16 was the commonest genotype in cases (54.5%, 12/22) and controls (66.7%, 46/69) (p = 0.30), followed by HPV18 (36.3%, 8/22 vs. 17.3% 12/69, respectively) (p = 0.08). Furthermore, 90% (20/22) of cases and 84.1% (58/69) of controls were positive for HPV16 or 18 (p = 0.42); 100% (22/22) of cases and 95.7% (66/69) of controls had at least one genotype targeted by the nonavalent vaccine (p = 0.3). The majority of HPV16 variants (87.3%, 48/55) were of European lineage. The proportion of unique nucleotide substitutions was significantly higher in cases (83.3%, 10/12) compared with controls (34.1%, 15/44), (p < 0.003, χ2, OR 9.7, 95%CI 1.7-97.7). CONCLUSIONS: Virological factors may account for the differences in CCs observed in younger compared with older women. All CCs in young women in this study had preventable 9vHPV types, which is important messaging for health provider adherence to new cervical screening guidelines.
Identifying and responding to family adversity in Australian community and primary health settings: a multi-site cross sectional study

Hall, T ; Constable, L ; Loveday, S ; Honisett, S ; Schreurs, N ; Goldfeld, S ; Loftus, H ; Jones, R ; Reupert, A ; Yap, MBH ; Woolfenden, S ; Montgomery, A ; Dalziel, K ; Bailey, C ; Pringle, G ; Fisher, J ; Forell, S ; Eapen, V ; Haslam, R ; Sanci, L ; Eastwood, J ; Hiscock, H (FRONTIERS MEDIA SA, 2023-09-13)

BACKGROUND: Unaddressed family adversity has potentially modifiable, negative biopsychosocial impacts across the life course. Little is known about how Australian health and social practitioners identify and respond to family adversity in community and primary health settings. OBJECTIVE: To describe, in two Australian community health services: (1) the number of adversities experienced by caregivers, (2) practitioner identification of caregivers experiencing adversity, (3) practitioner response to caregivers experiencing adversity, and (4) caregiver uptake of referrals. METHODS: Survey of caregivers of children aged 0-8 years attending community health services in Victoria and New South Wales (NSW). Analysis described frequencies of caregiver self-reported: (1) experiences of adversity, (2) practitioner identification of adversity, (3) practitioner response to adversity, and (4) referral uptake. Analyses were sub-grouped by three adversity domains and site. RESULTS: 349 caregivers (Victoria: n = 234; NSW: n = 115) completed the survey of whom 88% reported experiencing one or more family adversities. The median number of adversities was 4 (2-6). Only 43% of participants were directly asked about or discussed an adversity with a practitioner in the previous 6 months (Victoria: 30%; NSW: 68%). Among caregivers experiencing adversity, 30% received direct support (Victoria: 23%; NSW: 43%), and 14% received a referral (Victoria: 10%; NSW: 22%) for at least one adversity. Overall, 74% of caregivers accepted referrals when extended. CONCLUSION: The needs of Australian families experiencing high rates of adversity are not systematically identified nor responded to in community health services. This leaves significant scope for reform and enhancement of service responses to families experiencing adversity.
The Journey to Sustainable Participation in Physical Activity for Adolescents Living with Cerebral Palsy

Kilgour, G ; Stott, NS ; Steele, M ; Adair, B ; Hogan, A ; Imms, C (MDPI, 2023-09)

PURPOSE: To understand adolescents' and their parents' perspectives on 'being active', this study explored the experience of participation in physical activity (PA), the role of long-term participation in PA, and the importance of remaining active for life. METHODS: Eight ambulant adolescents with CP (aged 11-16 years, seven male) participated in a high-level mobility programme twice per week for 12 weeks. Guided using interpretive description, adolescents and 12 of their parents were interviewed before, after and nine months following the programme. Thirty-eight interviews were coded, analysed, and interpreted, informed by audit information, reflective journaling, and team discussions. RESULTS: Adolescents and their parents highly value being active now and into adulthood. Sustainable participation in PA requires adolescents and families to navigate complex environments (interpersonal, organisational, community, and policy). Core themes were: 'Just Doing it', 'Getting the Mix Right' (right people, right place, right time), 'Balancing the Continua' and 'Navigating the Systems'. The continua involved balancing intra-personal attributes: 'I will try anything' through to 'I will do it if I want to' and 'It's OK to be different' through to 'It sucks being disabled'. CONCLUSIONS: The journey to sustainable participation was complex and dynamic. Experiences of successful journeys are needed to help adolescents with CP "stay on track" to sustainable participation.
What happens when a whole-school health promotion research trial ends? a case study of the SEHER program in India

Shinde, S ; Raniti, M ; Sharma, A ; Sawyer, SM (FRONTIERS MEDIA SA, 2023-06-23)

BACKGROUND: Health promotion interventions that are developed and evaluated by researchers and other external providers are at risk of not being sustained beyond the initial implementation period. When delivered by a lay school health worker, the SEHER study of a whole-school health promotion intervention in Bihar, India was found to be feasible, acceptable and effective in improving school climate and student health behaviors. The objective of this case study is to describe the decision-making processes, barriers, and enablers to continuing the SEHER intervention following its official closure. METHODS: For this exploratory qualitative case study, data were collected from four government-run secondary schools, two of which continued SEHER and two of which discontinued it after official closure. Thirteen school staff were interviewed, and 100 girls and boys (aged 15-18 years old) participated in eight focus groups discussing their experiences of the process of continuing the intervention (or discontinuing) following its official closure. Thematic analysis was conducted in NVivo 12 using grounded theory. RESULTS: No school sustained the intervention as originally delivered in the research trial. In two schools, the intervention was adapted by selecting sustainable components, whereas in two others it was discontinued altogether. We identified four interrelated themes that explained the complex decision-making process, barriers, and enablers related to program continuation: (1) understanding of the intervention philosophy among school staff; (2) school capabilities to continue with intervention activities; (3) school attitudes and motivation about implementing the intervention, and; (4) the education policy environment and governance structures. Suggestions for overcoming barriers included adequate resource allocation; training, supervision, and support from external providers and the Ministry of Education; and formal government approval to continue the intervention. CONCLUSION: Sustaining this whole-school health promotion intervention in low-resource school settings in India depended on individual, school and government factors as well as external support. These findings suggest that health interventions will not necessarily become embedded in a school's operations merely because they are designed as a whole-school approach or because they are effective. Research should identify the resources and processes required to balance planning for future sustainability while awaiting trial results about an intervention's effectiveness.
Aicardi Syndrome Is a Genetically Heterogeneous Disorder

Ha, TT ; Burgess, R ; Newman, M ; Moey, C ; Mandelstam, SA ; Gardner, AE ; Ivancevic, AM ; Pham, D ; Kumar, R ; Smith, N ; Patel, C ; Malone, S ; Ryan, MM ; Calvert, S ; van Eyk, CL ; Lardelli, M ; Berkovic, SF ; Leventer, RJ ; Richards, LJ ; Scheffer, IE ; Gecz, J ; Corbett, MA (MDPI, 2023-08)

Aicardi Syndrome (AIC) is a rare neurodevelopmental disorder recognized by the classical triad of agenesis of the corpus callosum, chorioretinal lacunae and infantile epileptic spasms syndrome. The diagnostic criteria of AIC were revised in 2005 to include additional phenotypes that are frequently observed in this patient group. AIC has been traditionally considered as X-linked and male lethal because it almost exclusively affects females. Despite numerous genetic and genomic investigations on AIC, a unifying X-linked cause has not been identified. Here, we performed exome and genome sequencing of 10 females with AIC or suspected AIC based on current criteria. We identified a unique de novo variant, each in different genes: KMT2B, SLF1, SMARCB1, SZT2 and WNT8B, in five of these females. Notably, genomic analyses of coding and non-coding single nucleotide variants, short tandem repeats and structural variation highlighted a distinct lack of X-linked candidate genes. We assessed the likely pathogenicity of our candidate autosomal variants using the TOPflash assay for WNT8B and morpholino knockdown in zebrafish (Danio rerio) embryos for other candidates. We show expression of Wnt8b and Slf1 are restricted to clinically relevant cortical tissues during mouse development. Our findings suggest that AIC is genetically heterogeneous with implicated genes converging on molecular pathways central to cortical development.
Patients' Views on AI for Risk Prediction in Shared Decision-Making for Knee Replacement Surgery: Qualitative Interview Study

Gould, DJ ; Dowsey, MM ; Glanville-Hearst, M ; Spelman, T ; Bailey, JA ; Choong, PFM ; Bunzli, S (JMIR PUBLICATIONS, INC, 2023-09-18)

BACKGROUND: The use of artificial intelligence (AI) in decision-making around knee replacement surgery is increasing, and this technology holds promise to improve the prediction of patient outcomes. Ambiguity surrounds the definition of AI, and there are mixed views on its application in clinical settings. OBJECTIVE: In this study, we aimed to explore the understanding and attitudes of patients who underwent knee replacement surgery regarding AI in the context of risk prediction for shared clinical decision-making. METHODS: This qualitative study involved patients who underwent knee replacement surgery at a tertiary referral center for joint replacement surgery. The participants were selected based on their age and sex. Semistructured interviews explored the participants' understanding of AI and their opinions on its use in shared clinical decision-making. Data collection and reflexive thematic analyses were conducted concurrently. Recruitment continued until thematic saturation was achieved. RESULTS: Thematic saturation was achieved with 19 interviews and confirmed with 1 additional interview, resulting in 20 participants being interviewed (female participants: n=11, 55%; male participants: n=9, 45%; median age: 66 years). A total of 11 (55%) participants had a substantial postoperative complication. Three themes captured the participants' understanding of AI and their perceptions of its use in shared clinical decision-making. The theme Expectations captured the participants' views of themselves as individuals with the right to self-determination as they sought therapeutic solutions tailored to their circumstances, needs, and desires, including whether to use AI at all. The theme Empowerment highlighted the potential of AI to enable patients to develop realistic expectations and equip them with personalized risk information to discuss in shared decision-making conversations with the surgeon. The theme Partnership captured the importance of symbiosis between AI and clinicians because AI has varied levels of interpretability and understanding of human emotions and empathy. CONCLUSIONS: Patients who underwent knee replacement surgery in this study had varied levels of familiarity with AI and diverse conceptualizations of its definitions and capabilities. Educating patients about AI through nontechnical explanations and illustrative scenarios could help inform their decision to use it for risk prediction in the shared decision-making process with their surgeon. These findings could be used in the process of developing a questionnaire to ascertain the views of patients undergoing knee replacement surgery on the acceptability of AI in shared clinical decision-making. Future work could investigate the accuracy of this patient group's understanding of AI, beyond their familiarity with it, and how this influences their acceptance of its use. Surgeons may play a key role in finding a place for AI in the clinical setting as the uptake of this technology in health care continues to grow.
Exploring perinatal biopsychosocial factors and epigenetic age in 1-year-old offspring

Fransquet, PD ; Macdonald, JA ; Ryan, J ; Greenwood, CJ ; Olsson, CA (FUTURE MEDICINE LTD, 2023-09)

Background: Little is known about the determinants of epigenetic aging in pediatric populations. Methods: Epigenetic age was estimated from 258 1-year-olds, using pediatric buccal epigenetic and Horvath clocks. We explored associations between epigenetic age and maternal indicators of mental and relational health, substance use and general physical health assessed during trimester three. Results: Higher anxiety and stress, BMI and higher parent-parent relationship quality were associated with pediatric buccal epigenetic clock differences. High blood pressure during pregnancy was associated with Horvath age acceleration. Third-trimester smoking and pre-pregnancy weight were associated with acceleration and deceleration respectively, and concordant across clocks. Conclusion: A broad range of maternal factors may shape epigenetic age in infancy; further research is needed to explore the possible effects on health and development.
Addressing Child Mental Health Inequities Through Parental Mental Health and Preschool Attendance

Goldfeld, S ; Moreno-Betancur, M ; Gray, S ; Guo, S ; Downes, M ; O'Connor, E ; Azpitarte, F ; Badland, H ; Redmond, G ; Williams, K ; Woolfenden, S ; Mensah, F ; O'Connor, M (AMER ACAD PEDIATRICS, 2023-05)

BACKGROUND: Prevention is key to reducing socioeconomic inequities in children's mental health problems, especially given limited availability and accessibility of services. We investigated the potential to reduce inequities for disadvantaged children by improving parental mental health and preschool attendance in early childhood. METHODS: Data from the nationally representative birth cohort, Longitudinal Study of Australian Children (N = 5107, commenced in 2004), were used to examine the impact of socioeconomic disadvantage (0-1 year) on children's mental health problems (10-11 years). Using an interventional effects approach, we estimated the extent to which inequities could be reduced by improving disadvantaged children's parental mental health (4-5 years) and their preschool attendance (4-5 years). RESULTS: Disadvantaged children had a higher prevalence of elevated mental health symptoms (32.8%) compared with their nondisadvantaged peers (18.7%): confounder-adjusted difference in prevalence is 11.6% (95% confidence interval: 7.7% to 15.4%). Improving disadvantaged children's parental mental health and their preschool attendance to the level of their nondisadvantaged peers could reduce 6.5% and 0.3% of socioeconomic differences in children's mental health problems, respectively (equivalent to 0.8% and 0.04% absolute reductions). If these interventions were delivered in combination, a 10.8% (95% confidence interval: 6.9% to 14.7%) higher prevalence of elevated symptoms would remain for disadvantaged children. CONCLUSIONS: Targeted policy interventions that improve parental mental health and preschool attendance for disadvantaged children are potential opportunities to reduce socioeconomic inequities in children's mental health problems. Such interventions should be considered within a broader, sustained, and multipronged approach that includes addressing socioeconomic disadvantage itself.
A human model of Buruli ulcer: The case for controlled human infection and considerations for selecting a Mycobacterium ulcerans challenge strain

Muhi, S ; Osowicki, J ; O'Brien, D ; Johnson, PDR ; Pidot, S ; Doerflinger, M ; Marshall, JLL ; Pellegrini, M ; McCarthy, J ; Stinear, TPP ; Converse, PJ (PUBLIC LIBRARY SCIENCE, 2023-06)

Critical knowledge gaps regarding infection with Mycobacterium ulcerans, the cause of Buruli ulcer (BU), have impeded development of new therapeutic approaches and vaccines for prevention of this neglected tropical disease. Here, we review the current understanding of host-pathogen interactions and correlates of immune protection to explore the case for establishing a controlled human infection model of M. ulcerans infection. We also summarise the overarching safety considerations and present a rationale for selecting a suitable challenge strain.

Paediatrics (RCH) - Research Publications

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