Paediatrics (RCH) - Research Publications
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ItemThe global burden of adolescent and young adult cancer in 2019: a systematic analysis for the Global Burden of Disease Study 2019(ELSEVIER SCIENCE INC, 2022-01)BACKGROUND: In estimating the global burden of cancer, adolescents and young adults with cancer are often overlooked, despite being a distinct subgroup with unique epidemiology, clinical care needs, and societal impact. Comprehensive estimates of the global cancer burden in adolescents and young adults (aged 15-39 years) are lacking. To address this gap, we analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, with a focus on the outcome of disability-adjusted life-years (DALYs), to inform global cancer control measures in adolescents and young adults. METHODS: Using the GBD 2019 methodology, international mortality data were collected from vital registration systems, verbal autopsies, and population-based cancer registry inputs modelled with mortality-to-incidence ratios (MIRs). Incidence was computed with mortality estimates and corresponding MIRs. Prevalence estimates were calculated using modelled survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated as age-specific cancer deaths multiplied by the standard life expectancy at the age of death. The main outcome was DALYs (the sum of YLLs and YLDs). Estimates were presented globally and by Socio-demographic Index (SDI) quintiles (countries ranked and divided into five equal SDI groups), and all estimates were presented with corresponding 95% uncertainty intervals (UIs). For this analysis, we used the age range of 15-39 years to define adolescents and young adults. FINDINGS: There were 1·19 million (95% UI 1·11-1·28) incident cancer cases and 396 000 (370 000-425 000) deaths due to cancer among people aged 15-39 years worldwide in 2019. The highest age-standardised incidence rates occurred in high SDI (59·6 [54·5-65·7] per 100 000 person-years) and high-middle SDI countries (53·2 [48·8-57·9] per 100 000 person-years), while the highest age-standardised mortality rates were in low-middle SDI (14·2 [12·9-15·6] per 100 000 person-years) and middle SDI (13·6 [12·6-14·8] per 100 000 person-years) countries. In 2019, adolescent and young adult cancers contributed 23·5 million (21·9-25·2) DALYs to the global burden of disease, of which 2·7% (1·9-3·6) came from YLDs and 97·3% (96·4-98·1) from YLLs. Cancer was the fourth leading cause of death and tenth leading cause of DALYs in adolescents and young adults globally. INTERPRETATION: Adolescent and young adult cancers contributed substantially to the overall adolescent and young adult disease burden globally in 2019. These results provide new insights into the distribution and magnitude of the adolescent and young adult cancer burden around the world. With notable differences observed across SDI settings, these estimates can inform global and country-level cancer control efforts. FUNDING: Bill & Melinda Gates Foundation, American Lebanese Syrian Associated Charities, St Baldrick's Foundation, and the National Cancer Institute.
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ItemNo Preview AvailableCardiometabolic health markers among Aboriginal adolescents from the Next Generation Youth Wellbeing Cohort Study.(Elsevier BV, 2024-04)OBJECTIVE: The objective of this study was to investigate cardiometabolic health markers among Aboriginal adolescents aged 10-24 years and relationships with age, gender, and body composition. METHODS: Baseline data (2018-2020) from the Next Generation Youth Wellbeing Cohort Study (Western Australia, New South Wales, and Central Australia) on clinically assessed body mass index, waist/height ratio, blood pressure, glycated haemoglobin (HbA1c), total and high-density lipoprotein cholesterol, total/high-density lipoprotein cholesterol ratio, and triglycerides were analysed. RESULTS: Among 1100 participants, the proportion with individual health markers within the ideal range ranged from 59% for total cholesterol to 91% for HbA1c. Four percent had high blood pressure, which was more common with increasing age and among males; 1% had HbA1c indicative of diabetes. Healthier body composition (body mass index and waist/height ratio) was associated with having individual health markers in the ideal range and with an ideal cardiometabolic profile. CONCLUSIONS: Most Aboriginal adolescents in this study had cardiometabolic markers within the ideal range, though markers of high risk were present from early adolescence. Ideal health markers were more prevalent among those with healthy body composition. IMPLICATIONS FOR PUBLIC HEALTH: Specific screening and management guidelines for Aboriginal adolescents and population health initiatives that support maintenance of healthy body composition could help improve cardiometabolic health in this population.
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ItemNo Preview AvailableMethodological optimisation of thymocyte isolation and cryopreservation of human thymus samples(ELSEVIER, 2024-05)Premature lymphocytes develop into non-autoreactive, mature naïve CD4+ or CD8+ T cells in the thymus before entering the circulation. However, in-depth characterization of human thymocyte development remains challenging due to limited availability of human thymus samples and the fragile nature of thymocyte populations. Thymocytes often do not survive cryopreservation and thawing procedures, especially the fragile CD4+CD8+ double positive population. It is generally recommended to use fresh human thymus tissue on the day of excision to avoid any biases in thymocyte composition. This hampers the possibility to perform multiple experiments on the same thymus sample. To establish how the thymocyte viability and composition can be maintained, we compared two thymocyte isolation methods used for human and/or mice thymi, three cryopreservation methods in combination with our most gentle thawing technique. Based on our findings we established that fresh human thymi remain viable in cold storage for up to two days post-surgery without compromising thymocyte composition. Thymocytes can be cryopreserved if required, although the CD4+CD8+ double positive populations may be reduced. Our study provides thoroughly optimized methods to study human thymocyte development over a considerable time-frame post-surgery.
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ItemNo Preview AvailableUnderstanding cannabis use and mental health difficulties in context with women's experiences of stressful events and social health issues in pregnancy: The Aboriginal Families Study.(Elsevier BV, 2024-05)BACKGROUND: Few population-based data sources fully recognise the intersections between stressful events, social health issues, and cannabis use in pregnancy, and little is known about sequelae for women's mental health. METHODS: We draw on two waves of population-based data for 344 families participating in the Aboriginal Families Study longitudinal cohort. We examine women's mental health in the first year postpartum and when children were aged 5-9 years in context with life experiences and use of cannabis in pregnancy. OUTCOMES: One in five women (19·5%) used cannabis during pregnancy (with or without co-use of tobacco). Within this group of women, 88·3% experienced 3 or more (3+) stressful events or social health issues. Psychological distress (Kessler-5 scale, K-5) in the year postpartum was substantially higher amongst women who had used cannabis or experienced 3+ stressful events or social health issues. High proportions of women met criteria for support and referral for depression and/or anxiety (52·5% of women who had used cannabis compared to 20·9% amongst women who had neither used cannabis nor tobacco; 43·2% of women who had experienced 3+ stressful events or social health issues compared to 15·6% amongst women who had not indicated these experiences). Similar patterns of psychological distress, depressive (9-item adapted Personal Health Questionnaire, aPHQ-9) and anxiety symptoms (7-item Generalised Anxiety Disorder score, GAD-7) were evident when the study children were aged 5-9 years. INTERPRETATION: Amongst women who had used cannabis in pregnancy, a high burden of psychological distress, depression, and anxiety is evident in the postpartum period and as their children turn 5-9 years. The overlay of stressful events and social health issues and the high proportion of women meeting criteria for referral for mental health assessment and support indicate an urgent need to offer women opportunities for safe disclosure of cannabis use and opportunities to access sustained holistic services. Reducing the harms of cannabis use on Aboriginal and Torres Strait Islander families must be coupled with culturally safe ways of addressing the social, historical, and structural determinants of mental health distress and harmful use of substances.
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ItemNo Preview AvailableRapid and Accurate Diagnosis of Pediatric Tuberculosis Disease: A Diagnostic Accuracy Study for Pediatric Tuberculosis.(Ovid Technologies (Wolters Kluwer Health), 2023-05-01)INTRODUCTION: An estimated 1.2 million children develop tuberculosis (TB) every year with 240,000 dying because of missed diagnosis. Existing tools suffer from lack of accuracy and are often unavailable. Here, we describe the scientific and clinical methodology applied in RaPaed-TB, a diagnostic accuracy study. METHODS: This prospective diagnostic accuracy study evaluating several candidate tests for TB was set out to recruit 1000 children <15 years with presumptive TB in 5 countries (Malawi, Mozambique, South Africa, Tanzania, India). Assessments at baseline included documentation of TB signs and symptoms, TB history, radiography, tuberculin skin test, HIV testing and spirometry. Respiratory samples for reference standard testing (culture, Xpert Ultra) included sputum (induced/spontaneous) or gastric aspirate, and nasopharyngeal aspirate (if <5 years). For novel tests, blood, urine and stool were collected. All participants were followed up at months 1 and 3, and month 6 if on TB treatment or unwell. The primary endpoint followed NIH-consensus statements on categorization of TB disease status for each participant. The study was approved by the sponsor's and all relevant local ethics committees. DISCUSSION: As a diagnostic accuracy study for a disease with an imperfect reference standard, Rapid and Accurate Diagnosis of Pediatric Tuberculosis Disease (RaPaed-TB) was designed following a rigorous and complex methodology. This allows for the determination of diagnostic accuracy of novel assays and combination of testing strategies for optimal care for children, including high-risk groups (ie, very young, malnourished, children living with HIV). Being one of the largest of its kind, RaPaed-TB will inform the development of improved diagnostic approaches to increase case detection in pediatric TB.
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ItemCaries Detection in Primary Teeth Using Intraoral Scanners Featuring Fluorescence: Protocol for a Diagnostic Agreement Study(JMIR Publications, 2023)BACKGROUND: Digital methods that enable early caries identification can streamline data collection in research and optimize dental examinations for young children. Intraoral scanners are devices used for creating 3D models of teeth in dentistry and are being rapidly adopted into clinical workflows. Integrating fluorescence technology into scanner hardware can support early caries detection. However, the performance of caries detection methods using 3D models featuring color and fluorescence in primary teeth is unknown. OBJECTIVE: This study aims to assess the diagnostic agreement between visual examination (VE), on-screen assessment of 3D models in approximate natural colors with and without fluorescence, and application of an automated caries scoring system to the 3D models with fluorescence for caries detection in primary teeth. METHODS: The study sample will be drawn from eligible participants in a randomized controlled trial at the Royal Children's Hospital, Melbourne, Australia, where a dental assessment was conducted, including VE using the International Caries Detection and Assessment System (ICDAS) and intraoral scan using the TRIOS 4 (3Shape TRIOS A/S). Participant clinical records will be collected, and all records meeting eligibility criteria will be subject to an on-screen assessment of 3D models by 4 dental practitioners. First, all primary tooth surfaces will be examined for caries based on 3D geometry and color, using a merged ICDAS index. Second, the on-screen assessment of 3D models will include fluorescence, where caries will be classified using a merged ICDAS index that has been modified to incorporate fluorescence criteria. After 4 weeks, all examiners will repeat the on-screen assessment for all 3D models. Finally, an automated caries scoring system will be used to classify caries on primary occlusal surfaces. The agreement in the total number of caries detected per person between methods will be assessed using a Bland-Altman analysis and intraclass correlation coefficients. At a tooth surface level, agreement between methods will be estimated using multilevel models to account for the clustering of dental data. RESULTS: Automated caries scoring of 3D models was completed as of October 2023, with the publication of results expected by July 2024. On-screen assessment has commenced, with the expected completion of scoring and data analysis by March 2024. Results will be disseminated by the end of 2024. CONCLUSIONS: The study outcomes may inform new practices that use digital models to facilitate dental assessments. Novel approaches that enable remote dental examination without compromising the accuracy of VE have wide applications in the research environment, clinical practice, and the provision of teledentistry. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12622001237774; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=384632. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/51578.
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ItemEffectiveness of preventive treatment among different age groups and Mycobacterium tuberculosis infection status: a systematic review and individual-participant data meta-analysis of contact tracing studies(Elsevier BV, 2024-05-08)Background: Tuberculosis is a preventable disease. However, there is debate regarding which individuals would benefit most from tuberculosis preventive treatment and whether these benefits vary in settings with a high burden and low burden of tuberculosis. We aimed to compare the effectiveness of tuberculosis preventive treatment in exposed individuals of differing ages and Mycobacterium tuberculosis infection status while considering tuberculosis burden of the settings. Methods: In this systematic review and individual-participant meta-analysis, we investigated the development of incident tuberculosis in people closely exposed to individuals with tuberculosis. We searched for studies published between Jan 1, 1998, and April 6, 2018, in MEDLINE, Web of Science, BIOSIS, and Embase. We restricted our search to cohort studies; case-control studies and outbreak reports were excluded. Two reviewers evaluated titles, abstracts, and full text articles for eligibility. At each stage, two reviewers discussed discrepancies and re-evaluated articles until a consensus was reached. Individual-participant data and a pre-specified list of variables, including characteristics of the exposed contact, the index patient, and environmental characteristics, were requested from authors of all eligible studies; contacts exposed to a drug-resistant tuberculosis index patient were excluded. The primary study outcome was incident tuberculosis. We estimated adjusted hazard ratios (aHRs) for incident tuberculosis with mixed-effects Cox regression models with a study-level random effect. We estimated the number-needed-to-treat (NNT) to prevent one person developing tuberculosis. Propensity score matching procedures were used in all analyses. This study is registered with PROSPERO (CRD42018087022). Findings: After screening 25 358 records for eligibility, 439 644 participants from 32 cohort studies were included in the individual-participant data meta-analysis. Participants were followed for 1 396 413 person-years (median of 2·7 years [IQR 1·3–4.4]), during which 2496 people were diagnosed with incident tuberculosis. Overall, effectiveness of preventive treatment was 49% (aHR 0·51 [95% CI 0·44–0·60]). Participants with a positive tuberculin-skin-test (TST) or IFNγ release assay (IGRA) result at baseline benefitted from greater protection, regardless of age (0·09 [0·05–0·17] in children younger than 5 years, 0·20 [0·15–0·28] in individuals aged 5–17 years, and 0·17 [0·13–0·22] in adults aged 18 years and older). The effectiveness of preventive treatment was greater in high-burden (0·31 [0·23–0·40]) versus low-burden (0·58 [0·47–0·72]) settings. The NNT ranged from 9 to 34 depending on age among participants with a positive TST or IGRA in both high-burden and low-burden settings; among all contacts (regardless of TST or IGRA test result), the NNT ranged from 29 to 43 in high-burden settings and 213 to 455 in low-burden settings. Interpretation: Our findings suggest that a risk-targeted strategy prioritising contacts with evidence of M tuberculosis infection might be indicated in low-burden settings, and a broad approach including all contacts should be considered in high-burden settings. Preventive treatment was similarly effective among contacts of all ages.
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ItemChampioning Health at Hope Street(Council to Homeless Persons, 2024-04-17)Prevention and early intervention are vital to reducing homelessness among children and young people. For people under 25 experiencing homelessness and their children, access to timely healthcare is vital to wellbeing. These young people need to be supported through wrap-around service-delivery models that are child and youth specific and tailored to address their health needs. The largest cohort of homeless people in Australia are children and young people (0 to 24 years), making up 37.4 per cent of the homeless.
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ItemClinical outcomes in children living with HIV treated for non-severe tuberculosis in the SHINE Trial(Oxford University Press, 2024-04-09)BACKGROUND: Children living with HIV(CLWH) are at high risk of tuberculosis(TB) and face poor outcomes, despite antiretroviral treatment(ART). We evaluated outcomes in CLWH and HIV-uninfected children treated for non-severe TB in the SHINE trial. METHODS: SHINE was a randomized trial that enrolled children aged <16 years with smear-negative, non-severe TB who were randomized to receive 4 vs 6 months of TB treatment and followed for 72 weeks. We assessed TB relapse/recurrence, mortality, hospitalizations, grade ≥3 adverse events by HIV status, and HIV virological suppression in CLWH. RESULTS: Of 1204 enrolled, 127(11%) were CLWH, of similar age (median(IQR) 3.6(1.2, 10.3) vs. 3.5(1.5, 6.9)years, p= 0.07), but more underweight (WAZ; -2.3(-3.3, -0.8) vs -1.0(-1.8, -0.2), p<0.01) and anemic (hemoglobin 9.5(8.7, 10.9) vs 11.5(10.4, 12.3)g/dl, p<0.01) compared to HIV-uninfected children. 68(54%) CLWH were ART-naïve; baseline median CD4 count 719(241-1134) cells/mm3, CD4% 16(10-26)%). CLWH were more likely to be hospitalized (aOR=2.4(1.3-4.6)) and die (aHR(95%CI) 2.6(1.2,5.8)). HIV status, age <3 years (aHR 6.3(1.5,27.3)), malnutrition (aHR 6.2(2.4,15.9)) and hemoglobin <7g/dl(aHR 3.8(1.3,11.5) independently predicted mortality. Among children with available VL, 45% and 61% CLWH had VL<1000copies/ml at weeks 24 and 48, respectively. There was no difference in the effect of randomized treatment duration (4 vs 6 months) on TB treatment outcomes by HIV status (p for interaction=0.42). CONCLUSIONS: We found no evidence of a difference in TB outcomes between 4 and 6 months of treatment for CLWH treated for non-severe TB. Irrespective of TB treatment duration, CLWH had higher rates of mortality and hospitalization than HIV-uninfected counterparts.
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ItemNo Preview AvailableAdverse experiences in early intimate relationships and next-generation infant-mother attachment: findings from the ATP Generation 3 Study(WILEY, 2023-12)Abstract Chronic insecurities that emerge from adverse experiences in early intimate partner relationships in adolescence and emerging adulthood can have profound impacts on mental health and well‐being. Less clear is the extent to which these experiences for parents impact subsequent relationships within and across generations. We examine the extent to which secure, dismissing, pre‐occupied, and fearful intimate partner relationships in adolescence and emerging adulthood, well before becoming a parent, are associated with next‐generation patterns of attachment between mothers and infant offspring. Data were drawn from a nested study of infant–mother attachment (n = 220) within the Australian Temperament Project Generation 3 Study (N = 1167, est. 1983). Intimate partner relationships in adolescence and young adulthood were assessed by self‐report at 23–24 years of age. Over a decade later, infant–mother attachment security was assessed at 12 months post‐partum. Young adult intimate partner relationships defined by high levels of fearful, pre‐occupied, and dismissing attachment styles were reported in 11%, 17%, and 38% of young mothers, respectively. Increases in fear of intimacy in relationships were associated with an increase in the odds, by around 50%, of infant–mother insecure attachments (vs secure; OR = 1.56, 95% CI = 1.07, 2.28) and disorganised attachments (vs organised; OR = 1.49, 95% CI = 1.00, 2.22). A mother's self‐reported history of fear of intimacy within young adult relationships predicts later insecure and disorganised mother–infant attachments. Guidance and greater support for young people navigating their earliest intimate relationships may not only prevent adverse relational experiences at the time but also on becoming a parent. Findings have relevance for family and infant mental health therapies. Translating these findings into supported conversations may help prevent infant–mother attachment difficulties, or later repair them, through validation of the lingering effects of early fear of intimacy and empowerment of parents to prevent next‐generation infant experiences of distrust.