Paediatrics (RCH) - Research Publications
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ItemInformation systems for vaccine safety surveillance(TAYLOR & FRANCIS INC, 2022-09-15)Immunization implementation in the community relies upon post-licensure vaccine safety surveillance to maintain safe vaccination programs and to detect rare AEFI not observed in clinical trials. The increasing availability of electronic health-care related data and correspondence from both health-related providers and internet-based media has revolutionized health-care information. Many and varied forms of health information related to adverse event following immunization (AEFI) are potentially suitable for vaccine safety surveillance. The utilization of these media ranges from more efficient use of electronic spontaneous reporting, automated solicited surveillance methods, screening various electronic health record types, and the utilization of natural language processing techniques to scan enormous amounts of internet-based data for AEFI mentions. Each of these surveillance types have advantages and disadvantages and are often complementary to each other. Most are "hypothesis generating," detecting potential safety signals, where some, such as vaccine safety datalinking, may also serve as "hypothesis testing" to help verify and investigate those potential signals.
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ItemVaccine Adverse Event Mining of Twitter Conversations: 2-Phase Classification Study(JMIR PUBLICATIONS, INC, 2022-06-01)BACKGROUND: Traditional monitoring for adverse events following immunization (AEFI) relies on various established reporting systems, where there is inevitable lag between an AEFI occurring and its potential reporting and subsequent processing of reports. AEFI safety signal detection strives to detect AEFI as early as possible, ideally close to real time. Monitoring social media data holds promise as a resource for this. OBJECTIVE: The primary aim of this study is to investigate the utility of monitoring social media for gaining early insights into vaccine safety issues, by extracting vaccine adverse event mentions (VAEMs) from Twitter, using natural language processing techniques. The secondary aims are to document the natural language processing techniques used and identify the most effective of them for identifying tweets that contain VAEM, with a view to define an approach that might be applicable to other similar social media surveillance tasks. METHODS: A VAEM-Mine method was developed that combines topic modeling with classification techniques to extract maximal VAEM posts from a vaccine-related Twitter stream, with high degree of confidence. The approach does not require a targeted search for specific vaccine reaction-indicative words, but instead, identifies VAEM posts according to their language structure. RESULTS: The VAEM-Mine method isolated 8992 VAEMs from 811,010 vaccine-related Twitter posts and achieved an F1 score of 0.91 in the classification phase. CONCLUSIONS: Social media can assist with the detection of vaccine safety signals as a valuable complementary source for monitoring mentions of vaccine adverse events. A social media-based VAEM data stream can be assessed for changes to detect possible emerging vaccine safety signals, helping to address the well-recognized limitations of passive reporting systems, including lack of timeliness and underreporting.
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ItemSnotwatch: an ecological analysis of the relationship between febrile seizures and respiratory virus activity(BMC, 2022-06-22)BACKGROUND: Febrile seizures are the commonest type of seizure in occurring in the first few years of life, mostly affecting children aged six months to five years old. While largely benign, the incidence of each febrile seizure increases the risk of recurrence, afebrile seizures and epilepsy. Viruses are the most frequent cause of febrile illnesses in which a febrile seizure occurs. Febrile seizure presentation patterns appear to follow a seasonal trend. AIMS: To identify patterns of febrile seizure incidence across different seasons with specific viral activity, and to establish a framework for analysing virus circulation data with common illnesses within a shared region and population. SETTING: Our study was a study of febrile seizure presentations in Victoria, Australia and respiratory virus detection. PARTICIPANTS: We obtained independent datasets of emergency department febrile seizure presentations at Monash Health and all respiratory multiplex PCR tests performed at Monash Health from January 2010-December 2019 to observe common trends in virus circulation and febrile seizure incidence. STUDY DESIGN: Trends were studied temporally through mixed effects Poisson regression analysis of the monthly incidence of febrile seizures and the rate of positive PCR tests. Peak viral seasons (95th centile incidence) were compared to median viral circulation (50th centile incidence) to calculate peak season risk ratios. RESULTS: We found a 1.75-2.06 annual risk ratio of febrile seizure incidence in June-September. Temporal analysis of our data showed this peak in febrile seizures was attributable to circulating viruses in this season, and virus modelling showed correlation with increased rates of positive Influenza A (1.48 peak season risk ratio), Influenza B (1.31 peak season risk ratio), Human metapneumovirus (1.19 peak season risk ratio) and Respiratory Syncytial Virus (1.53 peak season risk ratio) on PCR testing. CONCLUSION: Our ecological study statistically demonstrates the recognised winter peak in febrile seizure incidence and ascribes the seasonal relationship to several viral infections which affect the community, including a novel association with Human metapneumovirus.
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ItemVictorian Specialist Immunisation Services (VicSIS) - bolstering adult clinics for COVID-19 vaccines(TAYLOR & FRANCIS INC, 2022-04-24)The Victorian Specialist Immunization Services (VicSIS) was established in Victoria, Australia, in February 2021, aiming to enhance vaccine safety services for Coronavirus disease (COVID-19) vaccines. VicSIS supports practitioners and patients with complex vaccine safety questions, including those who experience adverse events following immunization (AEFI) after COVID-19 vaccines. VicSIS provides individual vaccination recommendations, allergy testing, vaccine challenges, and vaccination under supervision. VicSIS initially comprised of eight adult COVID-19 specialist vaccination clinics, subsequently, expanding to better support pediatric patients as the Australian vaccine roll-out extended to adolescents and children. Since their establishment to September 2021, the inaugural VicSIS clinics received a total of 26,401 referrals and reviewed 6,079 patients. Consults were initially predominantly for pre-vaccination reviews, later predominantly becoming post-vaccination AEFI reviews as the program progressed. Regardless of the type of consult, the most common consult outcome was a recommendation for routine vaccination (73% and 55% of consult outcomes respectively). VicSIS is an integral component of the COVID-19 vaccination program and supports confidence in COVID-19 vaccine safety by providing consistent advice across the state. VicSIS aims to strengthen the health system through the pandemic, bolstering specialist immunization services beyond COVID-19 vaccines, including training the next generation of vaccinology experts.
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ItemNo Preview AvailableSurveillance for severe influenza and COVID-19 in patients admitted to sentinel Australian hospitals in 2020: the Influenza Complications Alert Network (FluCAN).(Australian Government Department of Health, 2022-03-28)INTRODUCTION: Influenza is a common cause of acute respiratory infection, and is a major cause of morbidity and mortality. Coronavirus disease 2019 (COVID-19) is an acute respiratory infection that emerged as a pandemic worldwide before the start of the 2020 Australian influenza season. This report summarises the epidemiology of hospitalisations with laboratory-confirmed influenza and COVID-19 during the 2020 influenza season in a sentinel surveillance system. METHODS: The Influenza Complications Alert Network (FluCAN) is a sentinel hospital-based surveillance program that operates at sites in all jurisdictions in Australia. Influenza and COVID-19 cases were defined as patients hospitalised at sentinel hospitals and confirmed by nucleic acid detection. RESULTS: There were 448 patients with COVID-19 admitted between 16 March and 31 December 2020, and only 20 patients with influenza admitted between 1 April and 30 November 2020, to one of 22 FluCAN hospitals. Of the COVID-19 cases, 173 (39%) were > 65 years of age, 36 (8%) were children (< 16 years), 6 (1%) were Aboriginal and Torres Strait Islander peoples, 4 (1%) were pregnant and 289 (65%) had chronic comorbidities. COVID-19 hospital admissions peaked between weeks 13 and 15 (first wave) nationally, and again between weeks 31 and 35 (Victoria), with most admissions represented by those above 40 years of age. DISCUSSION: There was an unusually low number of hospital admissions with laboratory-confirmed influenza in this season, compared to recent seasons. This is likely to be due to effective public health interventions and international border closures as a result of a rise in COVID-19 respiratory infections and associated hospitalisations.
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ItemAltered Behavior in Encephalitis: Insights From the Australian Childhood Encephalitis Study, 2013-2018(FRONTIERS MEDIA SA, 2021-12-24)Altered mental status is a major criterion for a diagnosis of encephalitis to be made with alteration in behavior, a key manifestation of altered mental status. We reviewed all evaluated cases identified by the Australian Childhood Encephalitis study between May 2013 and June 2018, to review the frequency and features of altered behavior (ALB). ALB was reported in >72% of cases of childhood encephalitis in all three major etiologic groups (infectious, immune-mediated, and unknown). The duration of ALB was >7 days in a minority, but significantly more frequent in immune-mediated compared with infectious encephalitis (27 and 10%, respectively, p < 0.01). ALB was most frequently characterized as irritability/agitation (47%), which predominated in children aged <1 year, and among the leading infectious causes in this age group (enterovirus, parechovirus, and bacterial meningoencephalitis). ALB in the form of disorientation/confusion (25%) was most prominent in those aged >1 year and most frequent in immune-mediated encephalitis. Hallucinations, paranoia, and aggression were all infrequent; suicidality/self-harm was not observed. ALB was reported in 20 of 21 cases of anti-N-methyl-d-aspartate receptor (anti-NMDAr), 19% for >7 days, and disorientation/confusion was the most frequent feature. Only one case was reported as presenting with "psychosis" and was diagnosed with anti-NMDAr encephalitis. Clinician-reported ALB is frequent but most often non-specific in childhood encephalitis. A longer duration of ALB is associated with an immune-mediated cause. More specific psychiatric symptoms (hallucinations, paranoia) are very infrequent. ALB is a hallmark of anti-NMDAr encephalitis, but psychosis is uncommon in contrast to the disorder in adults.
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ItemA Review of Febrile Seizures: Recent Advances in Understanding of Febrile Seizure Pathophysiology and Commonly Implicated Viral Triggers(FRONTIERS MEDIA SA, 2022-01-13)Febrile seizures are one of the commonest presentations in young children, with a 2-5% incidence in Western countries. Though they are generally benign, with rare long-term sequelae, there is much to be learned about their pathophysiology and risk factors. Febrile seizures are propagated by a variety of genetic and environmental factors, including viruses and vaccines. These factors must be taken into consideration by a clinician aiming to assess, diagnose and treat a child presenting with fevers and seizures, as well as to explain the sequelae of the febrile seizures to the concerned parents of the child. Our article provides an overview of this common childhood condition, outlining both the underlying mechanisms and the appropriate clinical approach to a child presenting with febrile seizures.
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ItemA case report describing the immune response of an infant with congenital heart disease and severe COVID-19.(Springer Science and Business Media LLC, 2021)BACKGROUND: Children with SARS-CoV-2 infection generally present with milder symptoms or are asymptomatic in comparison with adults, however severe disease occurs in a subset of children. To date, the immune correlates of severe COVID-19 in young children have been poorly characterised. METHODS: We report the kinetics of immune responses in relation to clinical and virological features in an infant with acute severe COVID-19 using high-dimensional flow cytometry and multiplex cytokine analysis. RESULTS: Systemic cellular and cytokine profiling show an initial increase in neutrophils and monocytes with depletion of lymphoid cell populations (particularly CD8 + T and NK cells) and elevated inflammatory cytokines. Expansion of memory CD4 + T (but not CD8 + T) cells occurred over time, with a predominant Th2 bias. Marked activation of T cell populations observed during the acute infection gradually resolved as the child recovered. Substantial in vitro activation of T-cell populations and robust cytokine production, in response to inactivated SARS-CoV-2 stimulation, was observed 3 months after infection indicating durable, long-lived cellular immune memory. CONCLUSIONS: These findings provide important insights into the immune response of a young infant with severe COVID-19 and will help to inform future research into therapeutic targets for high-risk groups.
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ItemInfluenza hospitalizations in Australian children 2010-2019: The impact of medical comorbidities on outcomes, vaccine coverage, and effectiveness(WILEY, 2021-11-16)BACKGROUND: Children with comorbidities are at greater risk of severe influenza outcomes compared with healthy children. In Australia, influenza vaccination was funded for those with comorbidities from 2010 and all children aged <5 years from 2018. Influenza vaccine coverage remains inadequate in children with and without comorbidities. METHODS: Children ≤16 years admitted with acute respiratory illness and tested for influenza at sentinel hospitals were evaluated (2010-2019). Multivariable regression was used to identify predictors of severe outcomes. Vaccine effectiveness was estimated using the modified incidence density test-negative design. RESULTS: Overall, 6057 influenza-confirmed hospitalized cases and 3974 test-negative controls were included. Influenza A was the predominant type (68.7%). Comorbidities were present in 40.8% of cases. Children with comorbidities were at increased odds of ICU admission, respiratory support, longer hospitalizations, and mortality. Specific comorbidities including neurological and cardiac conditions increasingly predisposed children to severe outcomes. Influenza vaccine coverage in influenza negative children with and without comorbidities was low (33.5% and 17.9%, respectively). Coverage improved following introduction of universal influenza vaccine programs for children <5 years. Similar vaccine effectiveness was demonstrated in children with (55% [95% confidence interval (CI): 45; 63%]) and without comorbidities (57% [(95%CI: 44; 67%]). CONCLUSIONS: Comorbidities were present in 40.8% of influenza-confirmed admissions and were associated with more severe outcomes. Children with comorbidities were more likely experience severe influenza with ICU admission, mechanical ventilation, and in-hospital morality. Despite demonstrated vaccine effectiveness in those with and without comorbidities, vaccine coverage was suboptimal. Interventions to increase vaccination are expected to reduce severe influenza outcomes.
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ItemA Learning Health System Framework to Operationalize Health Data to Improve Quality Care: An Australian Perspective(FRONTIERS MEDIA SA, 2021-10-27)Our healthcare system faces a burgeoning aging population, rising complexity, and escalating costs. Around 10% of healthcare is harmful, and evidence is slow to implement. Innovation to deliver quality and sustainable health systems is vital, and the methods are challenging. The aim of this study is to describe the process and present a perspective on a coproduced Learning Health System framework. The development of the Framework was led by publicly funded, collaborative, Academic Health Research Translation Centres, with a mandate to integrate research into healthcare to deliver impact. The focus of the framework is "learning together for better health," with coproduction involving leadership by an expert panel, a systematic review, qualitative research, a stakeholder workshop, and iterative online feedback. The coproduced framework incorporates evidence from stakeholders, from research, from data (practice to data and data to new knowledge), and from implementation, to take new knowledge to practice. This continuous learning approach aims to deliver evidence-based healthcare improvement and is currently being implemented and evaluated.