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Authors = Marc Modat

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14 pages, 2158 KiB  
Article
Illness Characteristics of COVID-19 in Children Infected with the SARS-CoV-2 Delta Variant
by Erika Molteni, Carole H. Sudre, Liane Dos Santos Canas, Sunil S. Bhopal, Robert C. Hughes, Liyuan Chen, Jie Deng, Benjamin Murray, Eric Kerfoot, Michela Antonelli, Mark Graham, Kerstin Kläser, Anna May, Christina Hu, Joan Capdevila Pujol, Jonathan Wolf, Alexander Hammers, Timothy D. Spector, Sebastien Ourselin, Marc Modat, Claire J. Steves, Michael Absoud and Emma L. Duncanadd Show full author list remove Hide full author list
Children 2022, 9(5), 652; https://doi.org/10.3390/children9050652 - 3 May 2022
Cited by 33 | Viewed by 4642
Abstract
Background: The Delta (B.1.617.2) SARS-CoV-2 variant was the predominant UK circulating strain between May and November 2021. We investigated whether COVID-19 from Delta infection differed from infection with previous variants in children. Methods: Through the prospective COVID Symptom Study, 109,626 UK school-aged children [...] Read more.
Background: The Delta (B.1.617.2) SARS-CoV-2 variant was the predominant UK circulating strain between May and November 2021. We investigated whether COVID-19 from Delta infection differed from infection with previous variants in children. Methods: Through the prospective COVID Symptom Study, 109,626 UK school-aged children were proxy-reported between 28 December 2020 and 8 July 2021. We selected all symptomatic children who tested positive for SARS-CoV-2 and were proxy-reported at least weekly, within two timeframes: 28 December 2020 to 6 May 2021 (Alpha (B.1.1.7), the main UK circulating variant) and 26 May to 8 July 2021 (Delta, the main UK circulating variant), with all children unvaccinated (as per national policy at the time). We assessed illness profiles (symptom prevalence, duration, and burden), hospital presentation, and presence of long (≥28 day) illness, and calculated odds ratios for symptoms presenting within the first 28 days of illness. Results: 694 (276 younger (5–11 years), 418 older (12–17 years)) symptomatic children tested positive for SARS-CoV-2 with Alpha infection and 706 (227 younger and 479 older) children with Delta infection. Median illness duration was short with either variant (overall cohort: 5 days (IQR 2–9.75) with Alpha, 5 days (IQR 2–9) with Delta). The seven most prevalent symptoms were common to both variants. Symptom burden over the first 28 days was slightly greater with Delta compared with Alpha infection (in younger children, 3 (IQR 2–5) symptoms with Alpha, 4 (IQR 2–7) with Delta; in older children, 5 (IQR 3–8) symptoms with Alpha, 6 (IQR 3–9) with Delta infection ). The odds of presenting several symptoms were higher with Delta than Alpha infection, including headache and fever. Few children presented to hospital, and long illness duration was uncommon, with either variant. Conclusions: COVID-19 in UK school-aged children due to SARS-CoV-2 Delta strain B.1.617.2 resembles illness due to the Alpha variant B.1.1.7., with short duration and similar symptom burden. Full article
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17 pages, 705 KiB  
Commentary
Emerging Treatments for Disorders of Consciousness in Paediatric Age
by Hassna Irzan, Marco Pozzi, Nino Chikhladze, Serghei Cebanu, Artashes Tadevosyan, Cornelia Calcii, Alexander Tsiskaridze, Andrew Melbourne, Sandra Strazzer, Marc Modat and Erika Molteni
Brain Sci. 2022, 12(2), 198; https://doi.org/10.3390/brainsci12020198 - 31 Jan 2022
Cited by 11 | Viewed by 5467
Abstract
The number of paediatric patients living with a prolonged Disorder of Consciousness (DoC) is growing in high-income countries, thanks to substantial improvement in intensive care. Life expectancy is extending due to the clinical and nursing management achievements of chronic phase needs, including infections. [...] Read more.
The number of paediatric patients living with a prolonged Disorder of Consciousness (DoC) is growing in high-income countries, thanks to substantial improvement in intensive care. Life expectancy is extending due to the clinical and nursing management achievements of chronic phase needs, including infections. However, long-known pharmacological therapies such as amantadine and zolpidem, as well as novel instrumental approaches using direct current stimulation and, more recently, stem cell transplantation, are applied in the absence of large paediatric clinical trials and rigorous age-balanced and dose-escalated validations. With evidence building up mainly through case reports and observational studies, there is a need for well-designed paediatric clinical trials and specific research on 0–4-year-old children. At such an early age, assessing residual and recovered abilities is most challenging due to the early developmental stage, incompletely learnt motor and cognitive skills, and unreliable communication; treatment options are also less explored in early age. In middle-income countries, the lack of rehabilitation services and professionals focusing on paediatric age hampers the overall good assistance provision. Young and fast-evolving health insurance systems prevent universal access to chronic care in some countries. In low-income countries, rescue networks are often inadequate, and there is a lack of specialised and intensive care, difficulty in providing specific pharmaceuticals, and lower compliance to intensive care hygiene standards. Despite this, paediatric cases with DoC are reported, albeit in fewer numbers than in countries with better-resourced healthcare systems. For patients with a poor prospect of recovery, withdrawal of care is inhomogeneous across countries and still heavily conditioned by treatment costs as well as ethical and cultural factors, rather than reliant on protocols for assessment and standardised treatments. In summary, there is a strong call for multicentric, international, and global health initiatives on DoC to devote resources to the paediatric age, as there is now scope for funders to invest in themes specific to DoC affecting the early years of the life course. Full article
(This article belongs to the Special Issue Emerging Treatments for Patients with Disorders of Consciousness)
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13 pages, 2283 KiB  
Article
Individualized Prognostic Prediction of the Long-Term Functional Trajectory in Pediatric Acquired Brain Injury
by Erika Molteni, Marta Bianca Maria Ranzini, Elena Beretta, Marc Modat and Sandra Strazzer
J. Pers. Med. 2021, 11(7), 675; https://doi.org/10.3390/jpm11070675 - 18 Jul 2021
Cited by 11 | Viewed by 3938
Abstract
In pediatric acquired brain injury, heterogeneity of functional response to specific rehabilitation treatments is a key confound to medical decisions and outcome prediction. We aimed to identify patient subgroups sharing comparable trajectories, and to implement a method for the early prediction of the [...] Read more.
In pediatric acquired brain injury, heterogeneity of functional response to specific rehabilitation treatments is a key confound to medical decisions and outcome prediction. We aimed to identify patient subgroups sharing comparable trajectories, and to implement a method for the early prediction of the long-term recovery course from clinical condition at first discharge. 600 consecutive patients with acquired brain injury (7.4 years ± 5.2; 367 males; median GCS = 6) entered a standardized rehabilitation program. Functional Independent Measure scores were measured yearly, until year 7. We classified the functional trajectories in clusters, through a latent class model. We performed single-subject prediction of trajectory membership in cases unseen during model fitting. Four trajectory types were identified (post.prob. > 0.95): high-start fast (N = 92), low-start fast (N = 168), slow (N = 130) and non-responders (N = 210). Fast responders were older (chigh = 1.8; clow = 1.1) than non-responders and suffered shorter coma (chigh = −14.7; clow = −4.3). High-start fast-responders had shorter length of stay (c = −1.6), and slow responders had lower incidence of epilepsy (c = −1.4), than non-responders (p < 0.001). Single-subject trajectory could be predicted with high accuracy at first discharge (accuracy = 0.80). In conclusion, we stratified patients based on the evolution of their response to a specific treatment program. Data at first discharge predicted the response over 7 years. This method enables early detection of the slow responders, who show poor post-acute functional gains, but achieve recovery comparable to fast responders by year 7. Further external validation in other rehabilitation programs is warranted. Full article
(This article belongs to the Section Epidemiology)
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12 pages, 8809 KiB  
Article
A Multi-Channel Uncertainty-Aware Multi-Resolution Network for MR to CT Synthesis
by Kerstin Klaser, Pedro Borges, Richard Shaw, Marta Ranzini, Marc Modat, David Atkinson, Kris Thielemans, Brian Hutton, Vicky Goh, Gary Cook, Jorge Cardoso and Sebastien Ourselin
Appl. Sci. 2021, 11(4), 1667; https://doi.org/10.3390/app11041667 - 12 Feb 2021
Cited by 11 | Viewed by 3435
Abstract
Synthesising computed tomography (CT) images from magnetic resonance images (MRI) plays an important role in the field of medical image analysis, both for quantification and diagnostic purposes. Convolutional neural networks (CNNs) have achieved state-of-the-art results in image-to-image translation for brain applications. However, synthesising [...] Read more.
Synthesising computed tomography (CT) images from magnetic resonance images (MRI) plays an important role in the field of medical image analysis, both for quantification and diagnostic purposes. Convolutional neural networks (CNNs) have achieved state-of-the-art results in image-to-image translation for brain applications. However, synthesising whole-body images remains largely uncharted territory, involving many challenges, including large image size and limited field of view, complex spatial context, and anatomical differences between images acquired at different times. We propose the use of an uncertainty-aware multi-channel multi-resolution 3D cascade network specifically aiming for whole-body MR to CT synthesis. The Mean Absolute Error on the synthetic CT generated with the MultiResunc network (73.90 HU) is compared to multiple baseline CNNs like 3D U-Net (92.89 HU), HighRes3DNet (89.05 HU) and deep boosted regression (77.58 HU) and shows superior synthesis performance. We ultimately exploit the extrapolation properties of the MultiRes networks on sub-regions of the body. Full article
(This article belongs to the Special Issue PET Imaging with Deep Learning)
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20 pages, 3615 KiB  
Article
Feasibility Randomized Trial for an Intensive Memory-Focused Training Program for School-Aged Children with Acquired Brain Injury
by Monica Recla, Erika Molteni, Valentina Manfredi, Filippo Arrigoni, Andrea Nordio, Susanna Galbiati, Valentina Pastore, Marc Modat and Sandra Strazzer
Brain Sci. 2020, 10(7), 430; https://doi.org/10.3390/brainsci10070430 - 7 Jul 2020
Cited by 2 | Viewed by 3446
Abstract
(1) Background: Memory deficits are common sequelae of pediatric Acquired Brain Injury (ABI). Only methods for non-focused cognitive remediation are available to the pediatric field. The aims of this feasibility trial are the description, implementation, and test of an intensive program specific to [...] Read more.
(1) Background: Memory deficits are common sequelae of pediatric Acquired Brain Injury (ABI). Only methods for non-focused cognitive remediation are available to the pediatric field. The aims of this feasibility trial are the description, implementation, and test of an intensive program specific to the training and re-adaptation of memory function in children, called Intensive Memory-Focused Training Program (IM-FTP); (2) Methods: Eleven children and adolescents with ABI (mean age at injury = 12.2 years, brain tumor survivors excluded) were clinically assessed and rehabilitated over 1-month through IM-FTP, including physio-kinesis/occupational, speech, and neuropsychology treatments. Each patient received a psychometric evaluation and a brain functional MRI at enrollment and at discharge. Ten pediatric controls with ABI (mean age at injury = 13.8 years) were clinically assessed, and rehabilitated through a standard program; (3) Results: After treatment, both groups had marked improvement in both immediate and delayed recall. IM-FTP was associated with better learning of semantically related and unrelated words, and larger improvement in immediate recall in prose memory. Imaging showed functional modification in the left frontal inferior cortex; (4) Conclusions: We described an age-independent reproducible multidisciplinary memory-focused rehabilitation protocol, which can be adapted to single patients while preserving inter-subject comparability, and is applicable up to a few months after injury. IM-FTP will now be employed in a powered clinical trial. Full article
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