ORCID Profile
0000-0003-2250-0594
Current Organisations
Aalborg University
,
Aarhus Universitet
,
National Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases
,
Sydney Children's Hospital
,
University of Sydney School of Public Health
,
University of Oxford
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Publications
Prevention of Tuberculosis in People Living with HIV
Publisher: Oxford University Press (OUP)
Date: 15-05-2010
DOI: 10.1086/651494
Abstract: Human immunodeficiency virus (HIV) infection drives tuberculosis (TB) incidence, and in some African countries, 80% of persons with TB have HIV infection. By the end of 2008, an estimated 33.2 million persons were infected with HIV, and in 2007, there were 2.7 million new HIV infections and 2 million HIV infection-related deaths. During the same year, there were 1.37 million (15%) cases of TB and HIV coinfection, resulting in 456,000 deaths. Prevention of TB requires prevention interventions for both HIV infection and TB, including HIV counseling and testing, disclosure and partner testing, behavior modification, earlier antiretroviral therapy, and the "Three I's for HIV/TB": isoniazid preventive treatment, intensified case finding, and infection control for TB. Managers of HIV programs should work with their colleagues in the TB field and the community to ensure that persons infected with HIV have access to the "Three I's for HIV/TB" as part of universal access to high-quality comprehensive prevention, care, and treatment of HIV infection and TB.
Ethical considerations regarding the effects of climate change and planetary health on children.
Publisher: Wiley
Date: 11-2021
DOI: 10.1111/JPC.15704
Abstract: Climate change represents one of the most significant health challenges and global inequities of our generation. As a 'wicked' problem, climate change imposes an involuntary exposure on vulnerable in iduals and societies that is regressive in its nature, with those least responsible for destroying planetary health at greatest risk of suffering the direct and indirect health consequences of unabated warming of the planet. The current and future generations of children are the most vulnerable population to suffer the effects of climate change. By 2030, there will be 131 000 additional child deaths each year if climate mitigation strategies are not enacted, driven by the synergy of an increasing burden of infectious diseases, food insecurity and political instability. Over half a billion of the world's children live in areas vulnerable to extreme weather events, and there is a pressing risk that our current lack of action to mitigate and adapt to climate change will result in today's children, and future generations, being the first to have poorer physical and mental health than previous generations - creating a significant intergenerational ethical dilemma. Child health-care professionals need to advocate for policies to address climate change that consider the complex health, planetary and ethical considerations necessary to solve the most significant risk to our children's health today. Without immediate action, the health of the current and future generations of children is perilous.
Predicting the causative pathogen among children with pneumonia using a causal Bayesian network
Publisher: Cold Spring Harbor Laboratory
Date: 02-07-2022
DOI: 10.1101/2022.07.01.22277170
Abstract: Pneumonia remains a leading cause of hospitalization and death among young children worldwide, and the diagnostic challenge of differentiating bacterial from non-bacterial pneumonia is the main driver of antibiotic use for treating pneumonia in children. Causal Bayesian networks (BNs) serve as powerful tools for this problem as they provide clear maps of probabilistic relationships between variables and produce results in an explainable way by incoporating both domain expert knowledge and numerical data. We used domain expert knowledge and data in combination and iteratively, to construct, parameterise and validate a causal BN to predict causative pathogens for childhood pneumonia. Expert knowledge elicitation occurred through a series of group workshops, surveys and one-on-one meetings involving 6-8 experts from erse domain areas. The model performance was evaluated based on both quantitative metrics (area under the receiver-operator curve (AUROC) and log loss) and qualitative expert validation. Sensitivity analyses were conducted to investigate how the target output is influenced by varying key assumptions of particular high degree of uncertainty around data or domain expert knowledge. Designed to apply to a cohort of children with X-ray confirmed pneumonia who presented to a tertiary paediatric hospital in Australia, the resulting BN offers explainable and quantitative predictions on a range of variables of interest, including the diagnosis of bacterial pneumonia, detection of respiratory pathogens in the nasopharynx, and the clinical phenotype of a pneumonia episode. Satisfactory numeric performance has been achieved including an AUROC of 0.8 in predicting the clinical diagnosis of bacterial pneumonia. Three commonly encountered scenarios were presented to demonstrate the potential usefulness of the BN outputs in various clinical pictures. To our knowledge, this is the first causal model developed to help determine the causative pathogen for paediatric pneumonia. It can be utilized to derive recommendations to support more directed and judicious use of antimicrobials for relevant cohorts. The BN needs further validation before it can be clinically implemented. Our model framework and the methodological approach can be adapted beyond our context to broad respiratory infections and geographical and healthcare settings.
Tuberculin skin test versus interferon-gamma release assay in refugee children: A retrospective cohort study
Publisher: Wiley
Date: 14-02-2018
DOI: 10.1111/JPC.13865
Abstract: The aim of this study was to assist clinicians evaluating refugee children for latent tuberculosis infection (LTBI) by comparing paired tuberculin skin test (TST) and Quantiferon Gold In-Tube (QGIT) test results with clinical management decisions and follow-up data in a large cohort of newly arrived refugee children. This was a retrospective analysis of all refugee children (<15 years of age) evaluated for LTBI with both TST and interferon-γ release assay between 2007 and 2010 in the Illawarra-Shoalhaven region of New South Wales, Australia. Demographics, country of origin, bacille Calmette-Guerin (BCG) vaccination status, chest X-ray results, TST and QGIT test results, clinical management and outcome on long-term follow-up were assessed. Of 272 children evaluated, complete results were available for 212 (78%). The vast majority (207 98%) were from Africa or Southeast Asia. Overall, 33 (16%) children were treated for LTBI 13 (39%) had concordant TST and QGIT results and 20 (61%) discordant results. Of 63 (30%) TST-positive (≥10 mm) children, 46 (73%) were QGIT assay-negative, 44 (70%) had a BCG scar, 3 (5%) were younger than 2 years and 6 (10%) were treated for LTBI. Of 32 QGIT assay-positive children, 15 (47%) were TST negative, 31 (97%) had a BCG scar, all were older than 2 years and 14 (44%) were treated for LTBI. Discordant TST and QGIT results were found in a high percentage of refugee children. QGIT is convenient and more specific than TST to diagnose LTBI in BCG-vaccinated children, although a careful tuberculosis exposure history and clinical assessment to rule out active disease remain important.
Antimicrobial resistance among children in sub-Saharan Africa.
Publisher: Elsevier BV
Date: 02-2017
Successful treatment of invasive carbapenemase-producing Enterobacteriaceae infections in children using carbapenem–aminoglycoside combination therapy: A case series
Publisher: Elsevier BV
Date: 11-2020
Expanding ART for Treatment and Prevention of HIV in South Africa: Estimated Cost and Cost-Effectiveness 2011-2050
Publisher: Public Library of Science (PLoS)
Date: 13-02-2012
IV and oral fosfomycin pharmacokinetics in neonates with suspected clinical sepsis
Publisher: Oxford University Press (OUP)
Date: 14-04-2021
DOI: 10.1093/JAC/DKAB083
Abstract: Fosfomycin has the potential to be re-purposed as part of a combination therapy to treat neonatal sepsis where resistance to current standard of care (SOC) is common. Limited data exist on neonatal fosfomycin pharmacokinetics and estimates of bioavailability and CSF lasma ratio in this vulnerable population are lacking. To generate data informing the appropriate dosing of IV and oral fosfomycin in neonates using a population pharmacokinetic analysis of plasma and CSF data. The NeoFosfo study (NCT03453177) was a randomized trial that examined the safety and pharmacokinetics of fosfomycin comparing SOC versus SOC plus fosfomycin. Sixty-one neonates received fosfomycin (100 mg/kg IV q12h for 48 h) and then they converted to oral therapy at the same dose. Two plasma pharmacokinetic s les were taken following the first IV and oral doses, s le times were randomized to cover the whole pharmacokinetic profile and opportunistic CSF pharmacokinetic s les were collected. A population pharmacokinetic model was developed in NONMEM and simulations were performed. In total, 238 plasma and 15 CSF concentrations were collected. A two-compartment disposition model, with an additional CSF compartment and first-order absorption, best described the data. Bioavailability was estimated as 0.48 (95% CI = 0.347–0.775) and the CSF lasma ratio as 0.32 (95% CI = 0.272–0.409). Allometric weight and postmenstrual age (PMA) scaling was applied additional covariates included postnatal age (PNA) on clearance and CSF protein on CSF lasma ratio. Through this analysis a population pharmacokinetic model has been developed that can be used alongside currently available pharmacodynamic targets to select a neonatal fosfomycin dose based on an infant’s PMA, PNA and weight.
Management Recommendations for Merkel Cell Carcinoma—A Danish Perspective
Publisher: MDPI AG
Date: 28-02-2020
Abstract: Merkel cell carcinoma (MCC) is a rare malignant neuroendocrine carcinoma of the skin with a poor prognosis and an apparent increase in incidence. Due to its rarity, evidence-based guidelines are limited, and there is a lack of awareness among clinicians. This review constitutes the consensus management recommendations developed by the Danish MCC expert group and is based on a systematic literature search. Patients with localized disease are recommended surgical excision and adjuvant radiotherapy to the primary site however, this may be omitted in patients with MCC with low risk features. Patients with regional lymph node involvement are recommended complete lymph node removal and adjuvant radiotherapy in case of extracapsular disease. Metastatic disease was traditionally treated with chemotherapy, however, recent clinical trials with immune therapy have been promising. Immune checkpoint inhibitors targeting the programmed cell death protein 1(PD-1) rogrammed death-ligand 1(PD-L1) axis should therefore be strongly considered as first-line treatment for fit patients. A 5-year follow-up period is recommended involving clinical exam every 3 months for 2 years and every 6 months for the following 3 years and PET-CT one to two times a year or if clinically indicated. These national recommendations are intended to offer uniform patient treatment and hopefully improve prognosis.
A single blinded, phase IV, adaptive randomised control trial to evaluate the safety of coadministration of seasonal influenza and COVID-19 vaccines (The FluVID study)
Publisher: Elsevier BV
Date: 10-2023
ENIGMA‐Sleep: Challenges, opportunities, and the road map
Publisher: Wiley
Date: 28-04-2021
DOI: 10.1111/JSR.13347
Abstract: Neuroimaging and genetics studies have advanced our understanding of the neurobiology of sleep and its disorders. However, in idual studies usually have limitations to identifying consistent and reproducible effects, including modest s le sizes, heterogeneous clinical characteristics and varied methodologies. These issues call for a large‐scale multi‐centre effort in sleep research, in order to increase the number of s les, and harmonize the methods of data collection, preprocessing and analysis using pre‐registered well‐established protocols. The Enhancing NeuroImaging Genetics through Meta‐Analysis (ENIGMA) consortium provides a powerful collaborative framework for combining datasets across in idual sites. Recently, we have launched the ENIGMA‐Sleep working group with the collaboration of several institutes from 15 countries to perform large‐scale worldwide neuroimaging and genetics studies for better understanding the neurobiology of impaired sleep quality in population‐based healthy in iduals, the neural consequences of sleep deprivation, pathophysiology of sleep disorders, as well as neural correlates of sleep disturbances across various neuropsychiatric disorders. In this introductory review, we describe the details of our currently available datasets and our ongoing projects in the ENIGMA‐Sleep group, and discuss both the potential challenges and opportunities of a collaborative initiative in sleep medicine.
What is the optimal antibiotic therapy for the treatment of non-tuberculous mycobacterial lymphadenitis in children?
Publisher: BMJ
Date: 21-10-2022
Clinical and Epidemiologic Profile of Invasive Pneumococcal Disease in Australian Children Following the Relaxation of Nonpharmaceutical Interventions Against SARS-COV-2.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 18-05-2023
DOI: 10.1097/INF.0000000000003972
Abstract: A global resurgence of invasive pneumococcal disease (IPD) has been noted in children. We provide a detailed clinical and epidemiological analysis of IPD in Australian children following relaxation of nonpharmaceutical interventions against coronavirus disease 2019, revealing significant morbidity and mortality—even in vaccinated children without known predisposing risk factors. Almost half of the IPD cases were caused by serotypes not covered by the 13-valent pneumococcal conjugate vaccine.
Impact of baseline and nadir neutrophil index in non-small cell lung cancer and ovarian cancer patients: Assessment of chemotherapy for resolution of unfavourable neutrophilia
Publisher: Springer Science and Business Media LLC
Date: 2013
COVID
‐19 in New South Wales children during 2021: severity and clinical spectrum
Publisher: Wiley
Date: 18-07-2022
DOI: 10.5694/MJA2.51661
What will it take to stop the needless deaths of millions of women and children each year?
Publisher: Wiley
Date: 05-2011
DOI: 10.1111/J.1440-1754.2010.01731.X
Abstract: Each year, almost 10 million children die before their fifth birthday the majority from easily preventable diseases such as diarrhoea, pneumonia and malaria. Furthermore, 10 million women endure pregnancy-related morbidities annually while 500,000 die in childbirth. The link between maternal and child health is inextricable and worldwide inequities continue to widen: 99% of all neonatal deaths occur in developing countries, while maternal mortality rates are 1,000 times greater for women in poor countries compared to those living in rich nations. These discrepancies [corrected] continue to persist despite the presence of a multitude of simple, cost-effective interventions which could save the lives of millions of women and children worldwide each year for a fraction of the cost associated spent on health care in the developed world.
Antibiotics needed to treat multidrug-resistant infections in neonates
Publisher: WHO Press
Date: 12-2022
SARS-CoV-2 in children: spectrum of disease, transmission and immunopathological underpinnings
Publisher: Elsevier BV
Date: 12-2020
The impact of climate change and biodiversity loss on the health of children: An ethical perspective.
Publisher: Frontiers Media SA
Date: 20-01-2023
DOI: 10.3389/FPUBH.2022.1048317
Abstract: The reality of human induced climate change is no longer in doubt, but the concerted global action required to address this existential crisis remains inexcusably inert. Together with climate change, bio ersity collapse is increasingly driving the emergence and spread of infectious diseases, the consequences of which are inequitable globally. Climate change is regressive in its nature, with those least responsible for destroying planetary health at greatest risk of suffering the direct and indirect health consequences. Over half a billion of the world's children live in areas vulnerable to extreme weather events. Without immediate action, the health of today's children and future generations will be compromised. We consider the impact of bio ersity collapse on the spread of infectious diseases and outline a duty of care along a continuum of three dimensions of medical ethics. From a medical perspective, the first dimension requires doctors to serve the best interests of their in idual patients. The second dimension considers the public health dimension with a focus on disease control and cost-effectiveness. The neglected third dimension considers our mutual obligation to the future health and wellbeing of children and generations to come. Given the adverse impact of our ecological footprint on current and future human health, we have a collective moral obligation to act.
Predicting the causative pathogen among children with pneumonia using a causal Bayesian network
Publisher: Public Library of Science (PLoS)
Date: 13-03-2023
DOI: 10.1371/JOURNAL.PCBI.1010967
Abstract: Pneumonia remains a leading cause of hospitalization and death among young children worldwide, and the diagnostic challenge of differentiating bacterial from non-bacterial pneumonia is the main driver of antibiotic use for treating pneumonia in children. Causal Bayesian networks (BNs) serve as powerful tools for this problem as they provide clear maps of probabilistic relationships between variables and produce results in an explainable way by incorporating both domain expert knowledge and numerical data. We used domain expert knowledge and data in combination and iteratively, to construct, parameterise and validate a causal BN to predict causative pathogens for childhood pneumonia. Expert knowledge elicitation occurred through a series of group workshops, surveys and one-on-one meetings involving 6-8 experts from erse domain areas. The model performance was evaluated based on both quantitative metrics and qualitative expert validation. Sensitivity analyses were conducted to investigate how the target output is influenced by varying key assumptions of a particularly high degree of uncertainty around data or domain expert knowledge. Designed to apply to a cohort of children with X-ray confirmed pneumonia who presented to a tertiary paediatric hospital in Australia, the resulting BN offers explainable and quantitative predictions on a range of variables of interest, including the diagnosis of bacterial pneumonia, detection of respiratory pathogens in the nasopharynx, and the clinical phenotype of a pneumonia episode. Satisfactory numeric performance has been achieved including an area under the receiver operating characteristic curve of 0.8 in predicting clinically-confirmed bacterial pneumonia with sensitivity 88% and specificity 66% given certain input scenarios (i.e., information that is available and entered into the model) and trade-off preferences (i.e., relative weightings of the consequences of false positive versus false negative predictions). We specifically highlight that a desirable model output threshold for practical use is very dependent upon different input scenarios and trade-off preferences. Three commonly encountered scenarios were presented to demonstrate the potential usefulness of the BN outputs in various clinical pictures. To our knowledge, this is the first causal model developed to help determine the causative pathogen for paediatric pneumonia. We have shown how the method works and how it would help decision making on the use of antibiotics, providing insight into how computational model predictions may be translated to actionable decisions in practice. We discussed key next steps including external validation, adaptation and implementation. Our model framework and the methodological approach can be adapted beyond our context to broad respiratory infections and geographical and healthcare settings.
The reality of the mortality statistics of the nurses' strike in Kenya.
Publisher: Elsevier BV
Date: 08-2017
Potential of fosfomycin in treating multidrug‐resistant infections in children
Publisher: Wiley
Date: 15-04-2020
DOI: 10.1111/JPC.14883
Simultaneous pharmacokinetic/pharmacodynamic (PKPD) assessment of ampicillin and gentamicin in the treatment of neonatal sepsis
Publisher: Oxford University Press (OUP)
Date: 23-11-2021
DOI: 10.1093/JAC/DKAB413
Abstract: This study aimed to simultaneously investigate the pharmacokinetics of icillin and gentamicin, currently the WHO standard of care for treating neonatal sepsis. Pharmacokinetic data were collected in 59 neonates receiving icillin and gentamicin for suspected or proven sepsis in the NeoFosfo trial (NCT03453177). A panel of 23 clinical Escherichia coli isolates from neonates with sepsis, resistant to either icillin, gentamicin or both, were tested for susceptibility using chequerboards. Pharmacokinetic harmacodynamic (PKPD) modelling and simulations were used to compare single-agent (EUCAST MIC) and combination (chequerboard MIC) target attainment with standard dosing regimens. A model was established that simultaneously estimated parameters of a one-compartment icillin model and a two-compartment gentamicin model. A common clearance for both drugs was used (6.89 L/h/70 kg) relating to glomerular filtration (CLGFR), with an additional clearance term added for icillin (5.3 L/h/70 kg). Covariate modelling included a priori allometric weight and post-menstrual age scaling of clearance. Further covariate relationships on renal clearance were postnatal age and serum creatinine. Simulation-based PKPD assessments suggest good Gram-positive (MIC ≤ 0.25 mg/L) cover. However, less than one-quarter of neonates were predicted to receive efficacious coverage against Enterobacterales (MIC ≤ 2 mg/L). The benefit of the icillin/gentamicin combination was limited, with only 2/23 E. coli clinical strains showing FIC index & 0.5 (synergy) and most in the range 0.5–1 (suggesting additivity). Simulations showed that feasible dosing strategies would be insufficient to cover resistant strains. PKPD simulations showed icillin and gentamicin combination therapy was insufficient to cover Enterobacterales, suggesting the need for alternative empirical treatment options for neonatal sepsis.
Guidelines for the treatment of severe acute malnutrition: a systematic review of the evidence for antimicrobial therapy
Publisher: Informa UK Limited
Date: 23-05-2018
Guidelines for the management of paediatric cholera infection: a systematic review of the evidence
Publisher: Informa UK Limited
Date: 23-05-2018
The potential of fosfomycin for multi-drug resistant sepsis: an analysis of in vitro activity against invasive paediatric Gram-negative bacteria
Publisher: Microbiology Society
Date: 05-2019
DOI: 10.1099/JMM.0.000973
Outcomes in multifocal neuroblastoma as part of the neurocristopathy syndrome
Publisher: American Academy of Pediatrics (AAP)
Date: 08-2014
Abstract: The neurocristopathy syndrome occurs because of a germline mutation of the paired-like homeobox 2b (PHOX2B) gene at 4p12, a neurogenesis regulator gene. The result is abnormal neural crest cell development resulting in congenital central hypoventilation syndrome, Hirschsprung disease, and neuroblastoma (NB), which is often multifocal and disseminated in its presentation. Previously, such widespread disease was regarded as highly aggressive and treated either with palliative intent or, conversely, with very intense, high-dose chemotherapy. We now present a patient who had neurocristopathy syndrome who had multifocal NB associated with an underlying germline PHOX2B mutation. He was treated conservatively with surgery and low-dose chemotherapy. After treatment he had extensive residual disease that has continued to mature despite no further treatment. A literature review identified 26 similar patients presenting with multifocal NB as part of the neurocristopathy syndrome. In all cases the NB behaved in an indolent manner with no deaths from tumor reported when patients received appropriate treatment. These provocative findings suggest for the first time that children who have neurocristopathy-associated NB should be treated conservatively, despite the aggressive appearance of their disease.
Coverage gaps in empiric antibiotic regimens used to treat serious bacterial infections in neonates and children in Southeast Asia and the Pacific
Publisher: Elsevier BV
Date: 10-2023
The first‐night effect and the consistency of short sleep in insomnia disorder
Publisher: Wiley
Date: 05-04-2023
DOI: 10.1111/JSR.13897
Abstract: The nature and degree of objective sleep impairments in insomnia disorder remain unclear. This issue is complicated further by potential changes in sleep architecture on the first compared with subsequent nights in the laboratory. Evidence regarding differential first‐night effects in people with insomnia disorder and controls is mixed. Here, we aimed to further characterize insomnia‐ and night‐related differences in sleep architecture. A comprehensive set of 26 sleep variables was derived from two consecutive nights of polysomnography in 61 age‐matched patients with insomnia and 61 good sleeper controls. People with insomnia expressed consistently poorer sleep than controls on several variables during both nights. While poorer sleep during the first night was observed in both groups, there were qualitative differences regarding the specific sleep variables expressing a first‐night effect. Short sleep (total sleep time 6 hr) was more likely during the first night and in insomnia, although approximately 40% of patients with insomnia presenting with short sleep on night 1 no longer met this criterion on night 2, which is important given the notion of short‐sleeping insomnia as a robust subtype.
Randomised controlled trial of fosfomycin in neonatal sepsis: pharmacokinetics and safety in relation to sodium overload
Publisher: BMJ
Date: 25-01-2022
DOI: 10.1136/ARCHDISCHILD-2021-322483
Abstract: To assess pharmacokinetics and changes to sodium levels in addition to adverse events (AEs) associated with fosfomycin among neonates with clinical sepsis. A single-centre open-label randomised controlled trial. Kilifi County Hospital, Kenya. 120 neonates aged ≤28 days admitted being treated with standard-of-care (SOC) antibiotics for sepsis: icillin and gentamicin between March 2018 and February 2019. We randomly assigned half the participants to receive additional intravenous then oral fosfomycin at 100 mg/kg two times per day for up to 7 days (SOC-F) and followed up for 28 days. Serum sodium, AEs and fosfomycin pharmacokinetics. 61 and 59 infants aged 0–23 days were assigned to SOC-F and SOC, respectively. There was no evidence of impact of fosfomycin on serum sodium or gastrointestinal side effects. We observed 35 AEs among 25 SOC-F participants and 50 AEs among 34 SOC participants during 1560 and 1565 infant-days observation, respectively (2.2 vs 3.2 events/100 infant-days incidence rate difference −0.95 events/100 infant-days (95% CI −2.1 to 0.20)). Four SOC-F and 3 SOC participants died. From 238 pharmacokinetic s les, modelling suggests an intravenous dose of 150 mg/kg two times per day is required for pharmacodynamic target attainment in most children, reduced to 100 mg/kg two times per day in neonates aged days or weighing g. Fosfomycin offers potential as an affordable regimen with a simple dosing schedule for neonatal sepsis. Further research on its safety is needed in larger cohorts of hospitalised neonates, including very preterm neonates or those critically ill. Resistance suppression would only be achieved for the most sensitive of organisms so fosfomycin is recommended to be used in combination with another antimicrobial. NCT03453177 .
Urinary tract infections in children
Publisher: Springer Science and Business Media LLC
Date: 08-08-2022
DOI: 10.1186/S12874-022-01695-6
Abstract: Diagnosing urinary tract infections (UTIs) in children in the emergency department (ED) is challenging due to the variable clinical presentations and difficulties in obtaining a urine s le free from contamination. Clinicians need to weigh a range of observations to make timely diagnostic and management decisions, a difficult task to achieve without support due to the complex interactions among relevant factors. Directed acyclic graphs (DAG) and causal Bayesian networks (BN) offer a way to explicitly outline the underlying disease, contamination and diagnostic processes, and to further make quantitative inference on the event of interest thus serving as a tool for decision support. We prospectively collected data on children present to ED with suspected UTIs. Through knowledge elicitation workshops and one-on-one meetings, a DAG was co-developed with clinical domain experts (the Expert DAG) to describe the causal relationships among variables relevant to paediatric UTIs. The Expert DAG was combined with prospective data and further domain knowledge to inform the development of an application-oriented BN (the Applied BN), designed to support the diagnosis of UTI. We assessed the performance of the Applied BN using quantitative and qualitative methods. We summarised patient background, clinical and laboratory characteristics of 431 episodes of suspected UTIs enrolled from May 2019 to November 2020. The Expert DAG was presented with a narrative description, elucidating how infection, specimen contamination and management pathways causally interact to form the complex picture of paediatric UTIs. Parameterised using prospective data and expert-elicited parameters, the Applied BN achieved an excellent and stable performance in predicting Escherichia coli culture results, with a mean area under the receiver operating characteristic curve of 0.86 and a mean log loss of 0.48 based on 10-fold cross-validation. The BN predictions were reviewed via a validation workshop, and we illustrate how they can be presented for decision support using three hypothetical clinical scenarios. Causal BNs created from both expert knowledge and data can integrate case-specific information to provide in idual decision support during the diagnosis of paediatric UTIs in ED. The model aids the interpretation of culture results and the diagnosis of UTIs, promising the prospect of improved patient care and judicious use of antibiotics.
Invasive aspergillosis in adult patients in Australia and New Zealand: 2017–2020
Publisher: Elsevier BV
Date: 11-2023
A single blinded, phase IV, adaptive randomised control trial to evaluate the safety of coadministration of seasonal influenza and COVID-19 vaccines (The FluVID study)
Publisher: Cold Spring Harbor Laboratory
Date: 20-06-2023
DOI: 10.1101/2023.06.14.23291380
Abstract: We evaluated the frequency of moderate and severe adverse events following coadministration of seasonal influenza vaccine (SIV) versus placebo with COVID-19 vaccines among adults to support practice guidelines. FluVID is a participant-blinded, phase IV, randomised control trial. On the same day as the participant’s scheduled COVID-19 vaccine, participants were randomised to receive SIV or saline placebo those assigned placebo at visit one then received SIV a week later, and vice versa. Self-reported adverse events were collected for daily seven days following each visit. The primary endpoint was any solicited adverse event of at least moderate severity occurring up to seven days following receipt of SIV or placebo. This was modelled using a Bayesian logistic regression model. Analyses were performed by COVID-19 vaccine type and dose number. Overall, 248 participants were enrolled of these, 195 had received BNT162b2 and 53 had received mRNA1273 COVID-19 vaccines according to national guidelines. After randomisation, 119 were assigned to receive SIV and 129 were assigned to receive placebo at visit one. Adverse events were most frequently reported as mild (grade 1) in nature. Among 142 BNT162b2 booster dose one and 43 BNT162b2 booster dose two recipients, the posterior median risk difference for moderate/severe adverse events following SIV versus placebo was 13% (95% credible interval [CrI] -0.03 to 0.27) and 13% (95%CrI -0.37 to 0.12), respectively. Among 18 mRNA1273 booster dose one and 35 mRNA1273 booster dose two recipients, the posterior median risk difference of moderate/severe adverse events following influenza vaccine versus placebo was 6% (95%CrI -0.29 to 0.41) and -4% (95%CrI -0.30 to 0.23), respectively. Adverse events following SIV and COVID-19 co-administration were generally mild and occurred with similar frequency to events following COVID-19 vaccine alone. We found no evidence to justify routine separation of SIV and COVID-19 vaccine doses. ACTRN12621001063808 The coadministration of mRNA COVID-19 and influenza vaccines typically resulted in mild events that were limited to 4 days. Frequency and nature of adverse events were similar to those in other randomised trials. This trial demonstrates a suitable design for evaluating vaccine schedules and coadministration.
Guidelines for the treatment of dysentery (shigellosis): a systematic review of the evidence
Publisher: Informa UK Limited
Date: 23-05-2018
Successful Use of Cefiderocol to Treat a Multidrug-resistant Stenotrophomonas maltophilia Ventilator-associated Pneumonia in an Extremely Preterm Neonate
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 24-07-2023
DOI: 10.1097/INF.0000000000004051
Abstract: Ventilator-associated pneumonia (VAP) caries a morbidity and mortality risk in the preterm neonate, particularly in the context of rising global antimicrobial resistance driving infections due to multidrug-resistant Gram-negative bacteria. Cefiderocol, a siderophilic cephalosporin, has broad Gram-negative antimicrobial activity and central nervous system penetration and is used for the treatment of hospital-acquired pneumonia or VAP in adults. Scarce data exists on its use in neonates. A female neonate born at 26 + 6 weeks developed VAP at 21 days of life. She was commenced on corticosteroids, vancomycin and ceftazidime but continued to deteriorate. Sputum cultures yielded Stenotrophomonas maltophilia resistant to trimethoprim/sulfamethoxazole, ciprofloxacin and ceftazidime, with potential susceptibility to cefiderocol. Cerebrospinal fluid showed an elevated white cell count. In view of worsening respiratory and hemodynamic status, antibiotic treatment was changed to cefiderocol monotherapy at 30 mg/kg/dose every 8 hours. Within 72 hours of commencing cefiderocol, the neonate was successfully extubated to variable-flow continuous positive airway pressure and showed ongoing clinical improvement. Cefiderocol was integral for the care of our neonate without any immediate adverse safety consequences. We relied on dosing data from a conference abstract, due to the paucity of evidence on the use of novel antimicrobials. This lack of evidence is particularly concerning given preterm neonates are particularly vulnerable to infections with multidrug-resistant Gram-negative organisms due to their immature immune systems, prolonged hospital stay, repeated interventions and antimicrobial exposure.
Malaria Prevention in Sub-Saharan Africa: A Field Study in Rural Uganda
Publisher: Springer Science and Business Media LLC
Date: 14-04-2009
DOI: 10.1007/S10900-009-9151-Y
Abstract: Malaria, a completely preventable and treatable disease, remains one of the biggest killers in Sub-Saharan Africa today. The objectives of this study were to describe the impact of malaria on a small rural community in Uganda (Bufuula) and to implement and evaluate a malaria prevention program (subsidised insecticide treated nets with an accompanying education session). In January 2006, a survey of 202 households (100% response rate) was conducted, and meetings held with the Village Council, which revealed that malaria was the community's major cause of morbidity and mortality, and showed there was a lack of access to preventative measures. Furthermore, 34% of each household's income was allocated to the burden of malaria. A malaria education and mosquito net distribution session was held in January 2006, which was attended by over 500 villagers who purchased 480 heavily-subsidised long lasting insecticide treated nets (LLINs). Home visits were conducted 1 week later to ensure the LLINs were hung correctly. A follow-up survey was conducted in January 2007. There was a rise in net ownership following the program (18% to 51%, P < 0.0001) and lower rates of childhood malaria prevalence (14%) than reported in Ugandan national statistics (40%). However, only half the nets owned were being used correctly by those most vulnerable to the illness. The findings suggest that mosquito nets must be provided with an effective education program and may be more successful if conducted in whole districts simultaneously rather than on a per-community basis. The evidence for super-targeting strategies for those most vulnerable is also considered. These findings provide important lessons and considerations for other wide-scale malaria prevention programs.
Monkeypox: A clinical update for paediatricians.
Publisher: Wiley
Date: 18-08-2022
DOI: 10.1111/JPC.16171
Abstract: The global spread of human monkeypox disease, a zoonotic infection related to smallpox and endemic to West and Central Africa, presents serious challenges for health systems. As of July 2022, 14 533 cases have been reported world-wide, leading to designation as a Public Health Emergency of International Concern. Monkeypox disease is spread from animals to humans through infected lesions or fluids human-human transmission occurs through fomites, droplets or direct contact. Illness is usually self-limiting, but severe disease can occur in specific groups - particularly children, and people who are immunocompromised or pregnant. Clinical presentation may include fever, lymphadenopathy and skin rash, but the rash may occur without other symptoms. Complications can include secondary bacterial infection of skin lesions, vision loss from corneal involvement, pneumonia, sepsis and encephalitis. Diagnosis of monkeypox requires consideration of epidemiological, clinical and laboratory findings, with sensitive history-taking, to elicit close contacts, critical. Supportive management is usually sufficient, but treatment options (where required) include antivirals and vaccinia immune globulin. A paucity of safety data for relevant antivirals may limit their use. There are two types of monkeypox vaccines: a replication-competent vaccinia vaccine, the use of which is logistically and clinically complex, and a replication-deficient modified vaccinia Ankara virus vaccine. Preparedness of health systems for addressing the current outbreak is constrained by historic underfunding for research, and compounded by stigma and discrimination against cases and affected communities. Key challenges in halting transmission include improving vaccine equity and countering discrimination against men who have sex with men to aid diagnosis and treatment.
A not so innocuous playground fall: lymphocutaneous nocardiosis in an immunocompetent boy
Publisher: BMJ
Date: 02-08-2022
Keeping It Real: Antibiotic Use Problems and Stewardship Solutions in Low- and Middle-income Countries
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-02-2022
State of the Mind: Growing up with HIV
Publisher: Springer Science and Business Media LLC
Date: 16-09-2020
Grading antimicrobial susceptibility data quality: room for improvement - Authors' reply.
Publisher: Elsevier BV
Date: 06-2018
Impact of climate change and biodiversity collapse on the global emergence and spread of infectious diseases.
Publisher: Wiley
Date: 11-2021
DOI: 10.1111/JPC.15681
Abstract: The reality of climate change and bio ersity collapse is irrefutable in the 21st century, with urgent action required not only to conserve threatened species but also to protect human life and wellbeing. This existential threat forces us to recognise that our existence is completely dependent upon well-functioning ecosystems that sustain the ersity of life on our planet, including that required for human health. By synthesising data on the ecology, epidemiology and evolutionary biology of various pathogens, we are gaining a better understanding of factors that underlie disease emergence and spread. However, our knowledge remains rudimentary with limited insight into the complex feedback loops that underlie ecological stability, which are at risk of rapidly unravelling once certain tipping points are breached. In this paper, we consider the impact of climate change and bio ersity collapse on the ever-present risk of infectious disease emergence and spread. We review historical and contemporaneous infectious diseases that have been influenced by human environmental manipulation, including zoonoses and vector- and water-borne diseases, alongside an evaluation of the impact of migration, urbanisation and human density on transmissible diseases. The current lack of urgency in political commitment to address climate change warrants enhanced understanding and action from paediatricians - to ensure that we safeguard the health and wellbeing of children in our care today, as well as those of future generations.
Harmonising regulatory approval for antibiotics in children
Publisher: Elsevier BV
Date: 02-2021
Costing Human Rights and Community Support Interventions as a Part of Universal Access to HIV Treatment and Care in a Southern African Setting
Publisher: Bentham Science Publishers Ltd.
Date: 09-2011
Related Organisations
National Centre For Immunisation Research And Surveillance Of Vaccine Preventable Diseases
Location: Australia
University Of Oxford
Location: United Kingdom of Great Britain and Northern Ireland
Related Funding Activities
No related grants have been discovered for Phoebe CM Williams.