ORCID Profile
0000-0002-6333-0109
Current Organisations
Infectious Diseases Data Observatory
,
University of Sydney
,
University of Oxford
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Publisher: Public Library of Science (PLoS)
Date: 29-03-2021
DOI: 10.1371/JOURNAL.PNTD.0009302
Abstract: Despite a historical association with poor tolerability, a comprehensive review on safety of antileishmanial chemotherapies is lacking. We carried out an update of a previous systematic review of all published clinical trials in visceral leishmaniasis (VL) from 1980 to 2019 to document any reported serious adverse events (SAEs). For this updated systematic review, we searched the following databases from 1 st Jan 2016 through 2 nd of May 2019: PUBMED, Embase, Scopus, Web of Science, Cochrane, clinicaltrials.gov, WHO ICTRP, and the Global Index Medicus. We included randomised and non-randomised interventional studies aimed at assessing therapeutic efficacy and extracted the number of SAEs reported within the first 30 days of treatment initiation. The incidence rate of death (IRD) from in idual treatment arms were combined in a meta-analysis using random effects Poisson regression. We identified 157 published studies enrolling 35,376 patients in 347 treatment arms. Pentavalent antimony was administered in 74 (21.3%), multiple-dose liposomal hotericin B (L-AmB) in 52 (15.0%), hotericin b deoxycholate in 51 (14.7%), miltefosine in 33 (9.5%), hotericin b fat/lipid/colloid/cholesterol in 31 (8.9%), and single-dose L-AmB in 17 (4.9%) arms. There was a total of 804 SAEs reported of which 793 (including 428 deaths) were extracted at study arm level (11 SAEs were reported at study level only). During the first 30 days, there were 285 (66.6%) deaths with the overall IRD estimated at 0.068 [95% confidence interval (CI): 0.041–0.114 I 2 = 81.4% 95% prediction interval (PI): 0.001–2.779] per 1,000 person-days at risk the rate was 0.628 [95% CI: 0.368–1.021 I 2 = 82.5%] in Eastern Africa, and 0.041 [95% CI: 0.021–0.081 I 2 = 68.1%] in the Indian Subcontinent. In 21 study arms which clearly indicated allowing the inclusion of patients with HIV co-infections the IRD was 0.575 [95% CI: 0.244–1.355 I 2 = 91.9%] compared to 0.043 [95% CI: 0.020–0.090 I 2 = 62.5%] in 160 arms which excluded HIV co-infections. Mortality within the first 30 days of VL treatment initiation was a rarely reported event in clinical trials with an overall estimated rate of 0.068 deaths per 1,000 person-days at risk, though it varied across regions and patient populations. These estimates may serve as a benchmark for future trials against which mortality data from prospective and pharmacovigilance studies can be compared. The methodological limitations exposed by our review support the need to assemble in idual patient data (IPD) to conduct robust IPD meta-analyses and generate stronger evidence from existing trials to support treatment guidelines and guide future research.
Publisher: Cold Spring Harbor Laboratory
Date: 19-03-2022
DOI: 10.1101/2022.03.17.484798
Abstract: Realizing the full utility of brain organoids as experimental systems to study human cortical development requires understanding whether organoids replicate the cellular and molecular events of this complex process precisely, reproducibly, and with fidelity to the embryo. Here we present a comprehensive single-cell transcriptomic, epigenetic, and spatial atlas of human cortical organoid development, comprising over 610,000 cells, spanning initial generation of neural progenitors through production of differentiated neuronal and glial subtypes. We define the lineage relationships and longitudinal molecular trajectories of cortical cell types during development in organoids, and show that developmental processes of cellular ersification in organoids correlate closely to endogenous ones, irrespective of metabolic state. Using this data, we identify genes with predicted human-specific roles in lineage establishment, and discover a developmental origin for the transcriptional ersity of human callosal projection neurons, a population that has undergone dramatic expansion and ersification during human evolution. Our work provides a comprehensive, single-cell molecular map of human corticogenesis in vitro , identifying developmental trajectories and molecular mechanisms associated with human cellular ersification.
Publisher: Wiley
Date: 27-06-2018
DOI: 10.1111/JNC.14338
Abstract: The cerebral cortex is a highly organized structure whose development depends on erse progenitor cell types, namely apical radial glia, intermediate progenitors, and basal radial glia cells, which are responsible for the production of the correct neuronal output. In recent years, these progenitor cell types have been deeply studied, particularly basal radial glia and their role in cortical expansion and gyrification. We review here a broad series of factors that regulate progenitor behavior and daughter cell fate. We first describe the different neuronal progenitor types, emphasizing the differences between lissencephalic and gyrencephalic species. We then review key factors shown to influence progenitor proliferation versus differentiation, discussing their roles in progenitor dynamics, neuronal production, and potentially brain size and complexity. Although spindle orientation has been considered a critical factor for mode of ision and daughter cell output, we discuss other features that are emerging as crucial for these processes such as organelle and cell cycle dynamics. Additionally, we highlight the importance of adhesion molecules and the polarity complex for correct cortical development. Finally, we briefly discuss studies assessing progenitor multipotency and its possible contribution to the production of specific neuronal populations. This review hence summarizes recent aspects of cortical progenitor cell biology, and pinpoints emerging features critical for their behavior.
Publisher: Public Library of Science (PLoS)
Date: 14-10-2021
DOI: 10.1371/JOURNAL.PNTD.0009858
Abstract: Scrub typhus is an acute febrile illness caused by intracellular bacteria from the genus Orientia . It is estimated that one billion people are at risk, with one million cases annually mainly affecting rural areas in Asia-Oceania. Relative to its burden, scrub typhus is understudied, and treatment recommendations vary with poor evidence base. These knowledge gaps could be addressed by establishing an in idual participant-level data (IPD) platform, which would enable pooled, more detailed and statistically powered analyses to be conducted. This study aims to assess the characteristics of scrub typhus treatment studies and explore the feasibility and potential value of developing a scrub typhus IPD platform to address unanswered research questions. We conducted a systematic literature review looking for prospective scrub typhus clinical treatment studies published from 1998 to 2020. Six electronic databases (Ovid Embase, Ovid Medline, Ovid Global Health, Cochrane Library, Scopus, Global Index Medicus), ClinicalTrials.gov, and WHO ICTRP were searched. We extracted data on study design, treatment tested, patient characteristics, diagnostic methods, geographical location, outcome measures, and statistical methodology. Among 3,100 articles screened, 127 were included in the analysis. 12,079 participants from 12 countries were enrolled in the identified studies. ELISA, PCR, and eschar presence were the most commonly used diagnostic methods. Doxycycline, azithromycin, and chlor henicol were the most commonly administered antibiotics. Mortality, complications, adverse events, and clinical response were assessed in most studies. There was substantial heterogeneity in the diagnostic methods used, treatment administered (including dosing and duration), and outcome assessed across studies. There were few interventional studies and limited data collected on specific groups such as children and pregnant women. There were a limited number of interventional trials, highlighting that scrub typhus remains a neglected disease. The heterogeneous nature of the available data reflects the absence of consensus in treatment and research methodologies and poses a significant barrier to aggregating information across available published data without access to the underlying IPD. There is likely to be a substantial amount of data available to address knowledge gaps. Therefore, there is value for an IPD platform that will facilitate pooling and harmonisation of currently scattered data and enable in-depth investigation of priority research questions that can, ultimately, inform clinical practice and improve health outcomes for scrub typhus patients.
Publisher: F1000 Research Ltd
Date: 20-03-2023
DOI: 10.12688/WELLCOMEOPENRES.19033.1
Abstract: Introduction: Noma (cancrum oris) is a devastating opportunistic infection resulting in severe tissue destruction that affects mouth and oro-facial structures. There are substantial gaps in our current knowledge and understanding of its aetiology, pathogenesis, prevention and treatment efficacy, as well as its distribution and burden. Although observed worldwide, the disease impacts the most vulnerable and marginalised populations, and is most reported in young children from sub-Saharan Africa. Noma often presents alongside conditions of extreme poverty, malnutrition and poor environmental sanitation. This protocol paper outlines the methodology for a systematic review planned to exhaustively synthesize the findings of the available noma literature. The project aims to generate an account of the present state of knowledge about the various aspects of noma to aid in framing effective strategies and interventions to curb this disease which disproportionately afflicts the poorest in society. Methods and analysis: The following databases have been searched by a medical librarian from database inception to 7 December 2022: OVID (MEDLINE/ Embase/ CAB abstracts/ Global Health), Scopus, Web of Science, African Index Medicus, African Journals Online: Health, French language search: Pascal, ClinicalTrials.gov, and WHO ICTRP. All primary research studies reporting on patients of any age diagnosed with noma will be eligible for inclusion in the review, including clinical trials, cohort studies, case-control, cross-sectional, other observational studies, case studies and case series. Data will be extracted from included studies to analyse the current evidence-based knowledge on the distribution, risk factors, microbiology, prevention and treatment modalities, and outcomes of noma. Ethics and dissemination: Results of this systematic review will be published in a peer-reviewed journal upon completion. PROSPERO Registration: CRD42019124839 (08/03/2019)
Publisher: F1000 Research Ltd
Date: 02-04-2020
DOI: 10.12688/WELLCOMEOPENRES.15821.1
Abstract: Since the coronavirus disease 2019 (COVID-19) outbreak was identified in December 2019 in Wuhan, China, a strong response from the research community has been observed with the proliferation of independent clinical trials assessing diagnostic methods, therapeutic and prophylactic strategies. While there is no intervention for the prevention or treatment of COVID-19 with proven clinical efficacy to date, tools to distil the current research landscape by intervention, level of evidence and those studies likely powered to address future research questions is essential. This living systematic review aims to provide an open, accessible and frequently updated resource summarising the characteristics of COVID-19 clinical trial registrations. Weekly search updates of the WHO International Clinical Trials Registry Platform (ICTRP) and source registries will be conducted. Data extraction by two independent reviewers of trial characteristic variables including categorisation of trial design, geographic location, intervention type and targets, level of evidence and intervention adaptability to low resource settings will be completed. Descriptive and thematic synthesis will be conducted. A searchable and interactive visualisation of the results database will be created, and made openly available online. Weekly results from the continued search updates will be published and made available on the Infectious Diseases Data Observatory (IDDO) website ( COVID-19 website ). This living systematic review will provide a useful resource of COVID-19 clinical trial registrations for researchers in a rapidly evolving context. In the future, this sustained review will allow prioritisation of research targets for in idual patient data meta-analysis.
Publisher: F1000 Research Ltd
Date: 25-01-2022
DOI: 10.12688/WELLCOMEOPENRES.17284.1
Abstract: Background: Many available medicines have been evaluated as potential repurposed treatments for coronavirus disease 2019 (COVID-19). We summarise the registered study landscape for 32 priority pharmacological treatments identified following consultation with external experts of the COVID-19 Clinical Research Coalition. Methods: All eligible trial registry records identified by systematic searches of the World Health Organisation International Clinical Trials Registry Platform as of 26 th May 2021 were reviewed and extracted. A descriptive summary of study characteristics was performed. Results: We identified 1,314 registered studies that included at least one of the 32 priority pharmacological interventions. The majority (1,043, 79%) were randomised controlled trials (RCTs). The s le size of the RCTs identified was typically small (median (25 th , 75 th percentile) s le size = 140 patients (70, 383)), i.e. in idually powered only to show very large effects. The most extensively evaluated medicine was hydroxychloroquine (418 registered studies). Other widely studied interventions were convalescent plasma (n=208), ritonavir (n=189) usually combined with lopinavir (n=181), and azithromycin (n=147). Very few RCTs planned to recruit participants in low-income countries (n=14 1.3%). A minority of studies (348, 26%) indicated a willingness to share in idual participant data. The living systematic review data are available at iddo.cognitive.city Conclusions: There are many registered studies planning to evaluate available medicines as potential repurposed treatments of COVID-19. Most of these planned studies are small, and therefore substantially underpowered for most relevant endpoints. Very few are large enough to have any chance of providing enough convincing evidence to change policies and practices. The sharing of in idual participant data (IPD) from these studies would allow pooled IPD meta-analyses which could generate definitive conclusions, but most registered studies did not indicate that they were willing to share their data.
Publisher: Public Library of Science (PLoS)
Date: 10-08-2021
DOI: 10.1371/JOURNAL.PNTD.0009650
Abstract: Reports on the occurrence and outcome of Visceral Leishmaniasis (VL) in pregnant women is rare in published literature. The occurrence of VL in pregnancy is not systematically captured and cases are rarely followed-up to detect consequences of infection and treatment on the pregnant women and foetus. A review of all published literature was undertaken to identify cases of VL infections among pregnant women by searching the following database: Ovid MEDLINE Ovid Embase Cochrane Database of Systematic Reviews Cochrane Central Register of Controlled Trials World Health Organization Global Index Medicus: LILACS (Americas) IMSEAR (South-East Asia) IMEMR (Eastern Mediterranean) WPRIM (Western Pacific) ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform. Selection criteria included any clinical reports describing the disease in pregnancy or vertical transmission of the disease in humans. Articles meeting pre-specified inclusion criteria and non-primary research articles such as textbook, chapters, letters, retrospective case description, or reports of accidental inclusion in trials were also considered. The systematic literature search identified 272 unique articles of which 54 records were included in this review a further 18 records were identified from additional search of the references of the included studies or from personal communication leading to a total of 72 records (71 case reports/case series 1 retrospective cohort study 1926–2020) describing 451 cases of VL in pregnant women. The disease was detected during pregnancy in 398 (88.2%), retrospectively confirmed after giving birth in 52 (11.5%), and the time of identification was not clear in 1 (0.2%). Of the 398 pregnant women whose infection was identified during pregnancy, 346 (86.9%) received a treatment, 3 (0.8%) were untreated, and the treatment status was not clear in the remaining 49 (12.3%). Of 346 pregnant women, Liposomal hotericin B (L-AmB) was administered in 202 (58.4%) and pentavalent antimony (PA) in 93 (26.9%). Outcomes were reported in 176 pregnant women treated with L-AmB with 4 (2.3%) reports of maternal deaths, 5 (2.8%) miscarriages, and 2 (1.1%) foetal death/stillbirth. For PA, outcomes were reported in 88 of whom 4 (4.5%) died, 24 (27.3%) had spontaneous abortion, 2 (2.3%) had miscarriages. A total of 26 cases of confirmed, probable or suspected cases of vertical transmission were identified with a median detection time of 6 months (range: 0–18 months). Outcomes of VL treatment during pregnancy is rarely reported and under-researched. The reported articles were mainly case reports and case series and the reported information was often incomplete. From the studies identified, it is difficult to derive a generalisable information on outcomes for pregnant women and babies, although reported data favours the usage of liposomal hotericin B for the treatment of VL in pregnant women.
Publisher: Public Library of Science (PLoS)
Date: 16-08-2021
DOI: 10.1371/JOURNAL.PNTD.0009697
Abstract: Chagas disease (CD), caused by the parasite Trypanosoma cruzi , affects ~6–7 million people worldwide. Significant limitations still exist in our understanding of CD. Harnessing in idual participant data (IPD) from studies could support more in-depth analyses to address the many outstanding research questions. This systematic review aims to describe the characteristics and treatment practices of clinical studies in CD and assess the breadth and availability of research data for the potential establishment of a data-sharing platform. This review includes prospective CD clinical studies published after 1997 with patients receiving a trypanocidal treatment. The following electronic databases and clinical trial registry platforms were searched: Cochrane Library, PubMed, Embase, LILACS, Scielo, Clintrials.gov, and WHO ICTRP. Of the 11,966 unique citations screened, 109 (0.9%) studies (31 observational and 78 interventional) representing 23,116 patients were included. Diagnosis for patient enrolment required 1 positive test result in 5 (4.6%) studies (2 used molecular method, 1 used molecular and serology, 2 used serology and parasitological methods), 2 in 60 (55.0%), 3 in 14 (12.8%) and 4 or more in 4 (3.7%) studies. A description of treatment regimen was available for 19,199 (83.1%) patients, of whom 14,605 (76.1%) received an active treatment and 4,594 (23.9%) were assigned to a placebo/no-treatment. Of the 14,605 patients who received an active treatment, benznidazole was administered in 12,467 (85.4%), nifurtimox in 825 (5.6%), itraconazole in 284 (1.9%), allopurinol in 251 (1.7%) and other drugs in 286 (1.9%). Assessment of efficacy varied largely and was based primarily on biological outcome parasitological efficacy relied on serology in 67/85 (78.8%) studies, molecular methods in 52/85 (61.2%), parasitological in 34/85 (40.0%), microscopy in 3/85 (3.5%) and immunohistochemistry in 1/85 (1.2%). The median time at which parasitological assessment was carried out was 79 days [interquartile range (IQR): 30–180] for the first assessment, 180 days [IQR: 60–500] for second, and 270 days [IQR: 18–545] for the third assessment. This review demonstrates the heterogeneity of clinical practice in CD treatment and in the conduct of clinical studies. The sheer volume of potential IPD identified demonstrates the potential for development of an IPD platform for CD and that such efforts would enable in-depth analyses to optimise the limited pharmacopoeia of CD and inform prospective data collection.
Publisher: F1000 Research Ltd
Date: 18-05-2022
DOI: 10.12688/WELLCOMEOPENRES.17739.1
Abstract: Introduction: Visceral leishmaniasis (VL) is a vector-borne disease caused by protozoan parasites of the genus Leishmania. The disease is endemic in parts of South Asia, East Africa, South America and the Mediterranean region, with an estimated 50,000 to 90,000 cases occurring annually. A living systematic review of existing scientific literature is proposed to identify clinical drug efficacy studies against VL, conducted following the Preferred Reporting Items for Systematic-Reviews and Meta-Analyses (PRISMA) guidelines. Methods and analysis: The proposed living systematic review builds on a previous systematic review first carried out in 2016, and the current protocol is designed to capture any published or registered VL clinical study from Nov-2021 onwards. The following databases will be searched by a medical librarian: PubMed, Ovid Embase, Scopus, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, clinicaltrials.gov, WHO ICTRP, as well as IMEMR, IMSEAR, and LILACS from the WHO Global Index Medicus. The systematic review will consider both randomised and non-randomised interventional studies, including single-armed studies. Ethics and dissemination: A database of eligible studies, including study characteristics, is openly available ( ool/vl-surveyor ) and will be continually updated every six months. All findings will be published in a peer-reviewed journal. PROSPERO registration: CRD42021284622 (29/11/2021)
Publisher: F1000 Research Ltd
Date: 02-06-2020
DOI: 10.12688/WELLCOMEOPENRES.15933.1
Abstract: Background: Since the coronavirus disease 2019 (COVID-19) outbreak was first reported in December 2019, many independent trials have been planned that aim to answer similar questions. Tools allowing researchers to review studies already underway can facilitate collaboration, cooperation and harmonisation. The Infectious Diseases Data Observatory (IDDO) has undertaken a living systematic review (LSR) to provide an open, accessible and frequently updated resource summarising characteristics of COVID-19 study registrations. Methods: Review of all eligible trial records identified by systematic searches as of 3 April 2020 and initial synthesis of clinical study characteristics were conducted. In partnership with Exaptive , an open access, cloud-based knowledge graph has been created using the results. Results: There were 728 study registrations which met eligibility criteria and were still active. Median (25 th , 75 th percentile) s le size was 130 (60, 400) for all studies and 134 (70, 300) for RCTs. Eight lower middle and low income countries were represented among the planned recruitment sites. Overall 109 pharmacological interventions or advanced therapy medicinal products covering 23 drug categories were studied. Majority (57%, 62/109) of them were planned only in one study arm, either alone or in combination with other interventions. There were 49 distinct combinations studied with 90% (44/49) of them administered in only one or two study arms. The data and interactive platform are available at iddo.cognitive.city/ . Conclusions: Baseline review highlighted that the majority of investigations in the first three months of the outbreak were small studies with unique treatment arms, likely to be unpowered to provide solid evidence. The continued work of this LSR will allow a more dependable overview of interventions tested, predict the likely strength of evidence generated, allow fast and informative filtering of relevant trials for specific user groups and provide the rapid guidance needed by investigators and funders to avoid duplication of efforts.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Brittany Jane Maguire.