ORCID Profile
0000-0002-9459-2566
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Publisher: European Respiratory Society (ERS)
Date: 10-2019
DOI: 10.1183/23120541.00248-2019
Abstract: Chronic wet cough, the most common symptom of a disease spectrum that encompasses protracted bacterial bronchitis (PBB) and bronchiectasis, is common among Aboriginal children. In the absence of any community prevalence data, and with the high burden of respiratory disease and the European Respiratory Society task force's recommendation to identify disease burden, we determined the prevalence of chronic wet cough and PBB in young Aboriginal children in four remote communities in north Western Australia. A whole-population, prospective study was conducted. Aboriginal children aged ≤7 years were clinically assessed for chronic wet cough by paediatric respiratory clinicians between July 2018 and May 2019. Where children had a wet cough but parents reported a short or uncertain cough duration, children were followed up 1 month later. A medical record audit 6 weeks to 3 months later was used to determine those children with chronic wet cough who had PBB (based on response to antibiotics). Of the 203 children, 191 (94% median age 3.5 years, range 0–7 years) were enrolled. At the initial visit, chronic wet cough was present in 21 (11%), absent in 143 (75%) and unknown in 27 (14%). By follow-up, the total prevalence of chronic wet cough was 13% (95% CI 8–19%) and 10% (95% CI 7–17%) for PBB. Chronic wet cough was more common in the two communities with unsealed roads (19%) compared to the two with sealed roads (7%). Given the relatively high prevalence, strategies to address reasons for and treatment of chronic wet cough and PBB in young Aboriginal children in remote north Western Australia are required.
Publisher: INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols
Date: 28-02-2023
DOI: 10.37766/INPLASY2023.2.0120
Abstract: Review question / Objective: The primary objective of the systematic review and meta-analysis is to determine whether TMPRSS2 inhibition with nafamostat or camostat mesylate is associated with a reduced risk of 30-day all-cause mortality in hospitalised and non-hospitalised adults with COVID-19. Condition being studied: Coronavirus disease 2019 (COVID-19). COVID-19 is an infectious disease caused by the SARS-CoV-2 virus. Most people infected with the virus will experience mild to moderate respiratory illness and recover without requiring special treatment. However, some will become seriously ill and require medical attention. Older people and those with underlying medical conditions like cardiovascular disease, diabetes, chronic respiratory disease, or cancer are more likely to develop serious illness. Anyone can get sick with COVID-19 and become seriously ill or die at any age.
Publisher: Springer Science and Business Media LLC
Date: 07-02-2023
DOI: 10.1186/S13063-023-07097-3
Abstract: While most Australian children are vaccinated, delays in vaccination can put them at risk from preventable infections. Widespread mobile phone ownership in Australia could allow automated short message service (SMS) reminders to be used as a low-cost strategy to effectively ‘nudge’ parents towards vaccinating their children on time. AuTOMATIC is an adaptive randomised trial which aims to both evaluate and optimise the use of SMS reminders for improving the timely vaccination of children at primary care clinics across Australia. The trial will utilise high levels of digital automation to effect, including eligibility assessment, randomisation, delivery of intervention, data extraction and analysis, thereby allowing healthcare-embedded trial delivery. Up to 10,000 parents attending participating primary care clinics will be randomised to one of 12 different active SMS vaccine reminder content and timing arms or usual practice only (no SMS reminder). The primary outcome is vaccine receipt within 28 days of the scheduled date for the index vaccine (the first scheduled vaccine after randomisation). Secondary analyses will assess receipt and timeliness for all vaccine occasions in all children. Regular scheduled analyses will be performed using Bayesian inference and pre-specified trial decision rules, enabling response adaptive randomisation, suspension of any poorly performing arms and early stopping if a single best message is identified. This study will aim to optimise SMS reminders for childhood vaccination in primary care clinics, directly comparing alternative message framing and message timing. We anticipate that the trial will be an exemplar in using Bayesian adaptive methodology to assess a readily implementable strategy in a wide population, capable of delivery due to the levels of digital automation. Methods and findings from this study will help to inform strategies for implementing reminders and embedding analytics in primary health care settings. ANZCTR: ACTRN12618000789268 .
Publisher: Informa UK Limited
Date: 29-06-2017
Publisher: Elsevier BV
Date: 2021
Publisher: Springer Science and Business Media LLC
Date: 14-12-2022
DOI: 10.1186/S13063-022-06929-Y
Abstract: SARS-CoV-2 infection is associated with a significant risk of hospitalisation, death, and prolonged impact on quality of life. Evaluation of new treatment options and optimising therapeutic management of people hospitalised with SARS-CoV-2 infection remains essential, but rapid changes in pandemic conditions and potential therapies have limited the utility of traditional approaches to randomised controlled trials. ASCOT ADAPT is an international, investigator-initiated, adaptive platform, randomised controlled trial of therapeutics for non-critically ill patients hospitalised with COVID-19. The study design is open label and pragmatic. Potential participants are hospitalised adults with PCR confirmed, symptomatic, SARS-CoV-2 infection, within 14 days of symptom onset. Domains include antiviral, antibody and anticoagulant interventions, with a composite primary outcome of 28-day mortality or progression to intensive-care level respiratory or haemodynamic support. Initial interventions include intravenous nafamostat and variable dose anticoagulation. A range of secondary endpoints, and substudies for specific domains and interventions are outlined. This paper presents the trial protocol and management structure, including international governance, remote site monitoring and biobanking activities and provides commentary on ethical and pragmatic considerations in establishing the ASCOT ADAPT trial under pandemic conditions. Australian and New Zealand Clinical Trials Registry (ACTRN12620000445976) and ClinicalTrials.gov (NCT04483960).
Publisher: Wiley
Date: 04-08-2017
DOI: 10.1111/AJO.12674
Abstract: As age is not modifiable, pregnancy risk information based on age alone is unhelpful for older women. To determine severe morbidity/mortality rates for women aged ≥35 years according to maternal profile based on parity, pre-existing medical conditions and prior pregnancy complications, and to assess the independent contribution of age. Population-based record-linkage study using NSW hospitalisation and birth records 2006-2012. Maternal and perinatal mortality/morbidity were assessed for non-anomalous singleton births to women aged ≥35 years. For 117 357 pregnancies among 99 375 women aged ≥35 years, the median age at delivery was 37 years (range 35-56 years), including: 35 652 (30.4%) multiparae without pre-existing medical or obstetric complications, 33,058 (28.2%) nulliparae without pre-existing medical conditions and 30 325 (25.8%) multiparae with prior pregnancy complications. Maternal and perinatal mortality/morbidity varied by maternal profile with ranges of 0.9-3.5% and 2.4-11.9%, respectively. For nulliparae, each five-year increase in age did not contribute significantly to maternal risk after controlling for medical conditions (adjustedodds ratio 1.08, 95% CI 0.93-1.25), but did confer perinatal risk (1.14 1.05-1.25). For multiparae, each five-year increase in age beyond 35 years was independently associated with adverse maternal (1.23 1.09-1.39) and perinatal outcomes (1.23 1.09-1.39). For women aged ≥35 years, presence of medical conditions conferred a greater risk for morbidity/mortality than age itself. For multiparous women, the effects of medical and obstetric history were additive. The contribution of maternal age to adverse outcomes in pregnancies without significant medical and obstetric history is modest.
Publisher: Springer Science and Business Media LLC
Date: 26-08-2020
DOI: 10.1186/S13063-020-04602-W
Abstract: The purpose of this double-blind, randomised, placebo-controlled, adaptive design trial with frequent interim analyses is to determine if Australian Indigenous children, who receive an additional (third) dose of human rotavirus vaccine (Rotarix, GlaxoSmithKline) for children aged 6 to 12 months, would improve protection against clinically significant all-cause gastroenteritis. Up to 1000 Australian Aboriginal and Torres Strait Islander (hereafter Indigenous) infants aged 6 to 12 months will be recruited from all regions of the Northern Territory. The intervention is the addition of a third scheduled dose of human monovalent rotavirus vaccine. ORVAC has two co-primary outcomes: (1) anti-rotavirus IgA seroconversion, defined as serum anti-rotavirus IgA ≥ 20 U/ml 28 to 55 days post Rotarix lacebo, and (2) time from randomisation to medical attendance for which the primary reason for presentation is acute gastroenteritis or acute diarrhoea illness before age 36 months. Secondary outcomes include (1) change in anti-rotavirus IgA log titre, (2) time from randomisation to hospitalisation with primary admission code presumed or confirmed acute diarrhoea illness before age 36 months, (3) time from randomisation to hospitalisation for which the admission is rotavirus confirmed diarrhoea illness before age 36 months and (4) time from randomisation to rotavirus infection (not necessarily requiring hospitalisation) meeting the jurisdictional definition before age 36 months. A detailed, prospective statistical analysis plan is presented for this Bayesian adaptive design. The plan was written by the trial statistician and details the study design, pre-specified adaptative elements, decision thresholds, statistical methods and the simulations used to evaluate the operating characteristics of the trial. As at August 2020, four interim analyses have been run, but no stopping rules have been triggered. Application of this SAP will minimise bias and supports transparent and reproducible research. Clinicaltrials.gov NCT02941107. Registered on 21 October 2016 10.1136/bmjopen-2019-032549
Publisher: Springer Science and Business Media LLC
Date: 11-04-2019
Publisher: BMJ
Date: 09-2023
Publisher: Elsevier BV
Date: 05-2020
Publisher: Elsevier BV
Date: 08-2020
Publisher: Springer Science and Business Media LLC
Date: 07-02-2022
DOI: 10.1186/S13063-021-05874-6
Abstract: The purpose of this double-blind, randomised, controlled trial is to compare allergic outcomes in children following vaccination with acellular pertussis (aP) antigen (standard of care in Australia) given at 2 months of age versus whole cell pertussis (wP) in the infant vaccine schedule. Up to 3000 Australian infants 6 to weeks of age born ≥32 weeks gestation. The intervention is a wP containing vaccine as the first scheduled pertussis vaccine dose instead of an aP containing vaccine. The primary outcome is a binary indicator of history of IgE-mediated food allergy at the age of 12 months confirmed, where necessary, with an oral food challenge before 18 months of age. Secondary outcomes include (1) history of parent-reported clinician-diagnosed new onset of atopic dermatitis by 6 or 12 months of age with a positive skin prick test to any allergen before 12 months of age, (2) geometric mean concentration in pertussis toxin-specific IgG before and 21 to 35 days after a booster dose of aP at 18 months of age, and (3) sensitisation to at least one allergen by 12 months of age. Operating characteristics of trial decision rules were evaluated by trial simulation. The selected rules for success and futility approximately maintain type I error of 0.05 and achieved power 0.85 for a reduction in the primary outcome from 10% in the control group to 7% in the intervention group. A detailed, prospective statistical analysis plan (SAP) is presented for this Bayesian adaptive design. The plan was written by the trial statistician and details the study design, pre-specified adaptive elements, decision thresholds, statistical methods, and the simulations used to evaluate the operating characteristics of the trial. Application of this SAP will minimise bias and supports transparent and reproducible research. Australia & New Zealand Clinical Trials Registry, ACTRN12617000065392 . Registered on 12 January 2017 10.1136/bmjopen-2020-042838
Publisher: Massachusetts Medical Society
Date: 24-01-2023
Publisher: Springer Science and Business Media LLC
Date: 14-12-2021
Publisher: BMJ
Date: 05-2020
DOI: 10.1136/BMJOPEN-2019-035992
Abstract: The purpose of this observational study is to assess the safety and impact of the introduction of a clinical practice guideline (CPG) recommending early discharge of infants with fever without source who are at low risk of serious bacterial infection (SBI). We hypothesise that implementation of this guideline will be associated with a rate of unplanned readmission to hospital (within 7 days of discharge) which is similar (ie, non-inferior) to that observed under previous standard practice. This observational study is a prospective pragmatic, multisite safety assessment and impact project. It will evaluate the safety of a CPG which allows febrile infants fulfilling low-risk criteria to be discharged early from hospital if their blood cultures demonstrate no growth at 24 hours (compared with previous minimum 48 hours admission). This guideline has been implemented at two Western Australian metropolitan hospitals. Infants aged months (chronological or corrected for premature birth before 37 weeks gestation) presenting with fever without source will be included. The primary outcome is readmission to hospital due to clinical deterioration/caregiver concern within 7 days of discharge, identified through review of electronic admission details and study-specific caregiver surveys. Secondary outcomes include rates of SBI, hospital lengths of stay compared with previous practice, clinician guideline adherence and caregiver satisfaction with the discharge process. Analysis will be within a sequential Bayesian safety monitoring framework, which incorporates new information and updates the evidence for guideline safety relative to previous practice (historical control) at prespecified interim analyses. Demographic and clinical information will be summarised. Ethics approval and waiver of consent for data collection has been granted by the Child and Adolescent Health Service Human Research Ethics Committee (RGS0000001415). Caregivers will have the option to opt out of survey follow-up. Results will be disseminated via peer-reviewed publication. Australian New Zealand Clinical Trials Registry (ACTRN12619001010189).
Publisher: American Academy of Pediatrics (AAP)
Date: 23-08-2023
DOI: 10.1542/HPEDS.2023-007160
Abstract: Despite evidence supporting earlier discharge of well-appearing febrile infants at low risk of serious bacterial infection (SBI), admissions for ≥48 hours remain common. Prospective safety monitoring may support broader guideline implementation. A sequential Bayesian safety monitoring framework was used to evaluate a new hospital guideline recommending early discharge of low-risk infants. Hospital readmissions within 7 days of discharge were regularly assessed against safety thresholds, derived from historic rates and expert opinion, and specified a priori (8 per 100 infants). Infants aged under 3 months admitted to 2 Western Australian metropolitan hospitals for management of fever without source were enrolled (August 2019–December 2021), to a prespecified maximum 500 enrolments. Readmission rates remained below the prespecified threshold at all scheduled analyses. Median corrected age was 34 days, and 14% met low-risk criteria (n = 71). SBI was diagnosed in 159 infants (32%), including urinary tract infection (n = 140) and bacteraemia (n = 18). Discharge occurred before 48 hours for 192 infants (38%), including 52% deemed low-risk. At study completion, 1 of 37 low-risk infants discharged before 48 hours had been readmitted (3%), for issues unrelated to SBI diagnosis. In total, 20 readmissions were identified (4 per 100 infants 95% credible interval 3, 6), with & .99 posterior probability of being below the prespecified noninferiority threshold, indicating acceptable safety. A Bayesian monitoring approach supported safe early discharge for many infants, without increased risk of readmission. This framework may be used to embed safety evaluations within future guideline implementation programs to further reduce low-value care.
No related grants have been discovered for James Totterdell.