Publications by authors named "P T Doran"

263 Publications

Prophylaxis in healthcare workers during a pandemic: a model for a multi-centre international randomised controlled trial using Bayesian analyses.

Trials 2022 Jun 27;23(1):534. Epub 2022 Jun 27.

University College Dublin - Clinical Research Centre at St. Vincent's University Hospital, Dublin, Ireland.

Background: Coronavirus disease 2019 (COVID-19) has exposed the disproportionate effects of pandemics on frontline workers and the ethical imperative to provide effective prophylaxis. We present a model for a pragmatic randomised controlled trial (RCT) that utilises Bayesian methods to rapidly determine the efficacy or futility of a prophylactic agent.

Methods: We initially planned to undertake a multicentre, phase III, parallel-group, open-label RCT, to determine if hydroxychloroquine (HCQ) taken once a week was effective in preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in healthcare workers (HCW) aged ≥ 18 years in New Zealand (NZ) and Ireland. Participants were to be randomised 2:1 to either HCQ (800 mg stat then 400 mg weekly) or no prophylaxis. The primary endpoint was time to Nucleic Acid Amplification Test-proven SARS-CoV-2 infection. Secondary outcome variables included mortality, hospitalisation, intensive care unit admissions and length of mechanical ventilation. The trial had no fixed sample size or duration of intervention. Bayesian adaptive analyses were planned to occur fortnightly, commencing with a weakly informative prior for the no prophylaxis group hazard rate and a moderately informative prior on the intervention log hazard ratio centred on 'no effect'. Stopping for expected success would be executed if the intervention had a greater than 0.975 posterior probability of reducing the risk of SARS-CoV-2 infection by more than 10%. Final success would be declared if, after completion of 8 weeks of follow-up (reflecting the long half-life of HCQ), the prophylaxis had at least a 0.95 posterior probability of reducing the risk of SARS-CoV-2 infection by more than 10%. Futility would be declared if HCQ was shown to have less than a 0.10 posterior probability of reducing acquisition of SARS-CoV-2 infection by more than 20%.

Discussion: This study did not begin recruitment due to the marked reduction in COVID-19 cases in NZ and concerns regarding the efficacy and risks of HCQ treatment in COVID-19. Nonetheless, the model presented can be easily adapted for other potential prophylactic agents and pathogens, and pre-established collaborative models like this should be shared and incorporated into future pandemic preparedness planning.

Trial Registration: The decision not to proceed with the study was made before trial registration occurred.
View Article and Find Full Text PDF

Download full-text PDF

Source Listing
June 2022

The Bioburden and Ionic Composition of Hypersaline Lake Ices: Novel Habitats on Earth and Their Astrobiological Implications.

Astrobiology 2022 08 7;22(8):962-980. Epub 2022 Jun 7.

Department of Geology and Geophysics, Louisiung State University, Baton Rouge, LA, USA.

We present thermophysical, biological, and chemical observations of ice and brine samples from five compositionally diverse hypersaline lakes in British Columbia's interior plateau. Possessing a spectrum of magnesium, sodium, sulfate, carbonate, and chloride salts, these low-temperature high-salinity lakes are analogs for planetary ice-brine environments, including the ice shells of Europa and Enceladus and ice-brine systems on Mars. As such, understanding the thermodynamics and biogeochemistry of these systems can provide insights into the evolution, habitability, and detectability of high-priority astrobiology targets. We show that biomass is typically concentrated in a layer near the base of the ice cover, but that chemical and biological impurities are present throughout the ice. Coupling bioburden, ionic concentration, and seasonal temperature measurements, we demonstrate that impurity entrainment in the ice is directly correlated to ice formation rate and parent fluid composition. We highlight unique phenomena, including brine supercooling, salt hydrate precipitation, and internal brine layers in the ice cover, important processes to be considered for planetary ice-brine environments. These systems can be leveraged to constrain the distribution, longevity, and habitability of low-temperature solar system brines-relevant to interpreting spacecraft data and planning future missions in the lens of both planetary exploration and planetary protection.
View Article and Find Full Text PDF

Download full-text PDF

Source Listing
August 2022

Neurophotonic tools for microscopic measurements and manipulation: status report.

Neurophotonics 2022 Jan 27;9(Suppl 1):013001. Epub 2022 Apr 27.

Yale School of Medicine, Department of Radiology and Biomedical Imaging, New Haven, Connecticut, United States.

was launched in 2014 coinciding with the launch of the BRAIN Initiative focused on development of technologies for advancement of neuroscience. For the last seven years, ' agenda has been well aligned with this focus on neurotechnologies featuring new optical methods and tools applicable to brain studies. While the BRAIN Initiative 2.0 is pivoting towards applications of these novel tools in the quest to understand the brain, this status report reviews an extensive and diverse toolkit of novel methods to explore brain function that have emerged from the BRAIN Initiative and related large-scale efforts for measurement and manipulation of brain structure and function. Here, we focus on neurophotonic tools mostly applicable to animal studies. A companion report, scheduled to appear later this year, will cover diffuse optical imaging methods applicable to noninvasive human studies. For each domain, we outline the current state-of-the-art of the respective technologies, identify the areas where innovation is needed, and provide an outlook for the future directions.
View Article and Find Full Text PDF

Download full-text PDF

Source Listing
January 2022

Identification of Distinct Long COVID Clinical Phenotypes Through Cluster Analysis of Self-Reported Symptoms.

Open Forum Infect Dis 2022 Apr 7;9(4):ofac060. Epub 2022 Mar 7.

Centre for Experimental Pathogen Host Research, University College Dublin, Dublin, Ireland.

Background: We aimed to describe the clinical presentation of individuals presenting with prolonged recovery from coronavirus disease 2019 (COVID-19), known as long COVID.

Methods: This was an analysis within a multicenter, prospective cohort study of individuals with a confirmed diagnosis of COVID-19 and persistent symptoms >4 weeks from onset of acute symptoms. We performed a multiple correspondence analysis (MCA) on the most common self-reported symptoms and hierarchical clustering on the results of the MCA to identify symptom clusters.

Results: Two hundred thirty-three individuals were included in the analysis; the median age of the cohort was 43 (interquartile range [IQR], 36-54) years, 74% were women, and 77.3% reported a mild initial illness. MCA and hierarchical clustering revealed 3 clusters. Cluster 1 had predominantly pain symptoms with a higher proportion of joint pain, myalgia, and headache; cluster 2 had a preponderance of cardiovascular symptoms with prominent chest pain, shortness of breath, and palpitations; and cluster 3 had significantly fewer symptoms than the other clusters (2 [IQR, 2-3] symptoms per individual in cluster 3 vs 6 [IQR, 5-7] and 4 [IQR, 3-5] in clusters 1 and 2, respectively;  < .001). Clusters 1 and 2 had greater functional impairment, demonstrated by significantly longer work absence, higher dyspnea scores, and lower scores in SF-36 domains of general health, physical functioning, and role limitation due to physical functioning and social functioning.

Conclusions: Clusters of symptoms are evident in long COVID patients that are associated with functional impairments and may point to distinct underlying pathophysiologic mechanisms of disease.
View Article and Find Full Text PDF

Download full-text PDF

Source Listing
April 2022