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 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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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.
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ItemEndophenotyping social cognition in the broader autism phenotype(WILEY, 2023-11-30)Relatives of individuals with autism spectrum disorder (ASD) may display milder social traits of the broader autism phenotype (BAP) providing potential endophenotypic markers of genetic risk for ASD. We performed a case-control comparison to quantify social cognition and pragmatic language difficulties in the BAP (n = 25 cases; n = 33 controls) using the Faux Pas test (FPT) and the Goldman-Eisler Cartoon task. Using deep phenotyping we then examined patterns of inheritance of social cognition in two large multiplex families and the spectrum of performance in 32 additional families (159 members; n = 51 ASD, n = 87 BAP, n = 21 unaffected). BAP individuals showed significantly poorer FPT performance and reduced verbal fluency with the absence of a compression effect in social discourse compared to controls. In multiplex families, we observed reduced FPT performance in 89% of autistic family members, 63% of BAP relatives and 50% of unaffected relatives. Across all affected families, there was a graded spectrum of difficulties, with ASD individuals showing the most severe FPT difficulties, followed by the BAP and unaffected relatives compared to community controls. We conclude that relatives of probands show an inherited pattern of graded difficulties in social cognition with atypical faux pas detection in social discourse providing a novel candidate endophenotype for ASD.
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ItemConfounding-adjustment methods for the causal difference in medians(BMC, 2023-12-07)BACKGROUND: With continuous outcomes, the average causal effect is typically defined using a contrast of expected potential outcomes. However, in the presence of skewed outcome data, the expectation (population mean) may no longer be meaningful. In practice the typical approach is to continue defining the estimand this way or transform the outcome to obtain a more symmetric distribution, although neither approach may be entirely satisfactory. Alternatively the causal effect can be redefined as a contrast of median potential outcomes, yet discussion of confounding-adjustment methods to estimate the causal difference in medians is limited. In this study we described and compared confounding-adjustment methods to address this gap. METHODS: The methods considered were multivariable quantile regression, an inverse probability weighted (IPW) estimator, weighted quantile regression (another form of IPW) and two little-known implementations of g-computation for this problem. Methods were evaluated within a simulation study under varying degrees of skewness in the outcome and applied to an empirical study using data from the Longitudinal Study of Australian Children. RESULTS: Simulation results indicated the IPW estimator, weighted quantile regression and g-computation implementations minimised bias across all settings when the relevant models were correctly specified, with g-computation additionally minimising the variance. Multivariable quantile regression, which relies on a constant-effect assumption, consistently yielded biased results. Application to the empirical study illustrated the practical value of these methods. CONCLUSION: The presented methods provide appealing avenues for estimating the causal difference in medians.
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ItemOn the use of multiple imputation to address data missing by design as well as unintended missing data in case-cohort studies with a binary endpoint(BMC, 2023-12-07)BACKGROUND: Case-cohort studies are conducted within cohort studies, with the defining feature that collection of exposure data is limited to a subset of the cohort, leading to a large proportion of missing data by design. Standard analysis uses inverse probability weighting (IPW) to address this intended missing data, but little research has been conducted into how best to perform analysis when there is also unintended missingness. Multiple imputation (MI) has become a default standard for handling unintended missingness and is typically used in combination with IPW to handle the intended missingness due to the case-control sampling. Alternatively, MI could be used to handle both the intended and unintended missingness. While the performance of an MI-only approach has been investigated in the context of a case-cohort study with a time-to-event outcome, it is unclear how this approach performs with a binary outcome. METHODS: We conducted a simulation study to assess and compare the performance of approaches using only MI, only IPW, and a combination of MI and IPW, for handling intended and unintended missingness in the case-cohort setting. We also applied the approaches to a case study. RESULTS: Our results show that the combined approach is approximately unbiased for estimation of the exposure effect when the sample size is large, and was the least biased with small sample sizes, while MI-only and IPW-only exhibited larger biases in both sample size settings. CONCLUSIONS: These findings suggest that a combined MI/IPW approach should be preferred to handle intended and unintended missing data in case-cohort studies with binary outcomes.
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ItemChanging climates, compounding challenges: a participatory study on how disasters affect the sexual and reproductive health and rights of young people in Fiji.(BMJ, 2023-12-16)Pacific youth are at the forefront of the climate crisis, which has important implications for their health and rights. Youth in Fiji currently bear a disproportionate burden of poor experiences and outcomes related to their sexual and reproductive health and rights (SRHR). There is limited information about how the increasing climate impacts may affect their SRHR, and what the implications may be for climate action and disaster risk reduction. We aimed to explore the experiences of 21 Fijian youth in fulfilling their SRHR when living through multiple natural hazards. We conducted 2 workshops and 18 individual semistructured interviews using visual and storytelling methods. Irrespective of the type of hazard or context of disasters, participants identified limited agency as the main challenge that increased SRHR risks. Through reflexive thematic analysis, we identified four themes centred around 'youth SRHR agency'; (1) information and knowledge, (2) community and belonging, (3) needs and resources, and (4) collective risks. These themes encompassed multiple factors that limited youth agency and increased their SRHR risks. Participants highlighted how existing challenges to their SRHR, such as access to SRHR information being controlled by community gatekeepers, and discrimination of sexual and gender diverse youth, were exacerbated in disasters. In disaster contexts, immediate priorities such as water, food and financial insecurity increased risks of transactional early marriage and transactional sex to access these resources. Daily SRHR risks related to normalisation of sexual and gender-based violence and taboos limited youth agency and influenced their perceptions of disasters and SRHR risks. Findings offer important insights into factors that limited youth SRHR agency before, during and after disasters. We underscore the urgency for addressing existing social and health inequities in climate and disaster governance. We highlight four key implications for reducing youth SRHR risks through whole-of-society approaches at multiple (sociocultural, institutional, governance) levels.
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ItemNo Preview AvailableTrusting relationships and learning together: A rapid review of Indigenous reference groups in Australian Indigenous health research(ELSEVIER SCIENCE INC, 2023-06)OBJECTIVE: This rapid review aims to identify how Indigenous research governance is conceptualised, implemented and documented within Australian Indigenous health research studies. METHODS: We searched for peer-reviewed English-language articles in two databases and for web-based grey literature published from database inception to November 2021. Reference lists were searched to identify additional articles. Data relating to research governance were extracted and analysed thematically. RESULTS: A total of 1120 records were screened, and 27 articles were included. Most articles providing detailed description of Indigenous research governance activities were qualitative studies (n=15, 55.6%). Key themes included members are experts; respectful relationships; flexibility; and key logistic considerations (nuts 'n' bolts). CONCLUSIONS: Although Indigenous research governance is recognised as an essential part of ethical research, activities and contributions made by Indigenous reference group (IRG) members are underreported. This important work needs greater visibility in the published literature to share best practice in Indigenous research governance that foregrounds Indigenous expert knowledge, perspectives, and experiences. IMPLICATIONS FOR PUBLIC HEALTH: The study provides a synthesis of factors to consider when establishing and facilitating an IRG for research with Indigenous communities. This has implications for researchers who can adapt and apply the findings to their practice.
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ItemNo Preview AvailableParental Mental Health and Parenting Behaviors Following Very Preterm Birth: Associations in Mothers and Fathers and Implications for Child Cognitive Outcome.(Oxford University Press (OUP), 2023-03-20)OBJECTIVES: To investigate the longitudinal associations between parental mental health symptoms within 4 weeks of birth, parenting behaviors at 1 year, and child general cognitive ability at 4.5-5 years in a sample of children born very preterm (VP). This study also examined whether these associations differed based on level of family social risk. METHODS: Participants were 143 children born <30 weeks' gestation and their parents. Within 4 weeks of birth, mothers' and fathers' depressive and anxiety symptoms were assessed using the Center for Epidemiologic Studies Depression Scale and Hospital Anxiety Depression Scale-Anxiety Subscale. Parents' sensitive and structuring parenting behaviors were assessed at 1 year using the Emotional Availability Scales. Child general cognitive ability was assessed at 4.5-5 years using the Wechsler Preschool & Primary Scale of Intelligence-Fourth Edition. RESULTS: Higher maternal depressive symptoms were associated with lower levels of sensitive and structuring parenting behavior, while higher maternal anxiety symptoms were associated with higher levels of structuring parenting behavior. There was weak evidence for positive associations between mothers' sensitive parenting behavior and fathers' structuring parenting behavior and child general cognitive ability. There was also weak evidence for stronger associations between mothers' mental health symptoms, parenting behaviors, and child general cognitive ability, in families of higher compared with lower social risk. CONCLUSIONS: Depressive and anxiety symptoms experienced by mothers in the initial weeks following VP birth can have long-term effects on their parenting behaviors. Enquiring about parents' mental health during their child's hospitalization in the neonatal intensive care unit is crucial.