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| 5. |
- Lane, C. A., et al.
(författare)
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Study protocol: Insight 46-a neuroscience sub-study of the MRC National Survey of Health and Development
- 2017
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Ingår i: Bmc Neurology. - : Springer Science and Business Media LLC. - 1471-2377. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Background: Increasing age is the biggest risk factor for dementia, of which Alzheimer's disease is the commonest cause. The pathological changes underpinning Alzheimer's disease are thought to develop at least a decade prior to the onset of symptoms. Molecular positron emission tomography and multi-modal magnetic resonance imaging allow key pathological processes underpinning cognitive impairment -including a-amyloid depostion, vascular disease, network breakdown and atrophy -to be assessed repeatedly and non-invasively. This enables potential determinants of dementia to be delineated earlier, and therefore opens a pre-symptomatic window where intervention may prevent the onset of cognitive symptoms. Methods/design: This paper outlines the clinical, cognitive and imaging protocol of "Insight 46", a neuroscience sub-study of the MRC National Survey of Health and Development. This is one of the oldest British birth cohort studies and has followed 5362 individuals since their birth in England, Scotland and Wales during one week in March 1946. These individuals have been tracked in 24 waves of data collection incorporating a wide range of health and functional measures, including repeat measures of cognitive function. Now aged 71 years, a small fraction have overt dementia, but estimates suggest that similar to 1/3 of individuals in this age group may be in the preclinical stages of Alzheimer's disease. Insight 46 is recruiting 500 study members selected at random from those who attended a clinical visit at 60-64 years and on whom relevant lifecourse data are available. We describe the sub-study design and protocol which involves a prospective two time-point (0, 24 month) data collection covering clinical, neuropsychological, beta-amyloid positron emission tomography and magnetic resonance imaging, biomarker and genetic information. Data collection started in 2015 (age 69) and aims to be completed in 2019 (age 73). Discussion: Through the integration of data on the socioeconomic environment and on physical, psychological and cognitive function from 0 to 69 years, coupled with genetics, structural and molecular imaging, and intensive cognitive and neurological phenotyping, Insight 46 aims to identify lifetime factors which influence brain health and cognitive ageing, with particular focus on Alzheimer's disease and cerebrovascular disease. This will provide an evidence base for the rational design of disease-modifying trials.
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| 6. |
- Sudre, C. H., et al.
(författare)
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Symptom clusters in COVID-19 : A potential clinical prediction tool from the COVID Symptom Study app
- 2021
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 7:12
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Tidskriftsartikel (refereegranskat)abstract
- As no one symptom can predict disease severity or the need for dedicated medical support in coronavirus disease 2019 (COVID-19), we asked whether documenting symptom time series over the first few days informs outcome. Unsupervised time series clustering over symptom presentation was performed on data collected from a training dataset of completed cases enlisted early from the COVID Symptom Study Smartphone application, yielding six distinct symptom presenta- tions. Clustering was validated on an independent replication dataset between 1 and 28 May 2020. Using the first 5 days of symptom logging, the ROC-AUC (receiver operating characteristic – area under the curve) of need for respiratory sup- port was 78.8%, substantially outperforming personal characteristics alone (ROC-AUC 69.5%). Such an approach could be used to monitor at-risk patients and predict medical resource requirements days before they are required.
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| 8. |
- Drew, David A., et al.
(författare)
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Aspirin and NSAID use and the risk of COVID-19
- 2021
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Early reports raised concern that use of non-steroidal anti-inflammatory drugs (NSAIDs) may increase risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19). Users of the COVID Symptom Study smartphone application reported use of aspirin and other NSAIDs between March 24 and May 8, 2020. Users were queried daily about symptoms, COVID-19 testing, and healthcare seeking behavior. Cox proportional hazards regression was used to determine the risk of COVID-19 among according to aspirin or non-aspirin NSAID users. Among 2,736,091 individuals in the U.S., U.K., and Sweden, we documented 8,966 incident reports of a positive COVID-19 test over 60,817,043 person-days of follow-up. Compared to non-users and after stratifying by age, sex, country, day of study entry, and race/ethnicity, non-aspirin NSAID use was associated with a modest risk for testing COVID-19 positive (HR 1.23 [1.09, 1.32]), but no significant association was observed among aspirin users (HR 1.13 [0.92, 1.38]). After adjustment for lifestyle factors, comorbidities and baseline symptoms, any NSAID use was not associated with risk (HR 1.02 [0.94, 1.10]). Results were similar for those seeking healthcare for COVID-19 and were not substantially different according to lifestyle and sociodemographic factors or after accounting for propensity to receive testing. Our results do not support an association of NSAID use, including aspirin, with COVID-19 infection. Previous reports of a potential association may be due to higher rates of comorbidities or use of NSAIDs to treat symptoms associated with COVID-19.One Sentence Summary NSAID use is not associated with COVID-19 risk.Competing Interest StatementJW, RD, and JC are employees of Zoe Global Ltd. TDS is a consultant to Zoe Global Ltd. DAD and ATC previously served as investigators on a clinical trial of diet and lifestyle using a separate mobile application that was supported by Zoe Global Ltd. Other authors have no conflict of interest to declare.Clinical TrialNCT04331509Funding StatementZoe provided in kind support for all aspects of building running and supporting the app and service to all users worldwide. DAD is supported by the National Institute of Diabetes and Digestive and Kidney Diseases K01DK120742. CGG is supported by the Bau Tsu Zung Bau Kwan Yeu Hing Research and Clinical Fellowship. LHN is supported by the American Gastroenterological Association Research Scholars Award. ATC is the Stuart and Suzanne Steele MGH Research Scholar and Stand Up to Cancer scientist. The Massachusetts Consortium on Pathogen Readiness (MassCPR) and Mark and Lisa Schwartz supported MGH investigators (DAD CGG LHN ADJ WM RSM CHL SK ATC). CMA is supported by the NIDDK K23 DK120899 and the Boston Childrens Hospital Office of Faculty Development Career Development Award. Kings College of London investigators (KAL MNL TV MSG CHS SO CJS TDS) were supported by the Wellcome Trust and EPSRC (WT212904/Z/18/Z WT203148/Z/16/Z T213038/Z/18/Z) the NIHR GSTT/KCL Biomedical Research Centre MRC/BHF (MR/M016560/1) UK Research and Innovation London Medical Imaging and Artificial Intelligence Centre for Value Based Healthcare and the Alzheimers Society (AS-JF-17-011). MNL is supported by an NIHR Doctoral Fellowship (NIHR300159). Work related to the Swedish elements of the study are supported by grants from the Swedish Research Council, Swedish Heart-Lung Foundation and the Swedish Foundation for Strategic Research (LUDC-IRC 15-0067). Sponsors had no role in study design analysis and interpretation of data report writing and the decision to submit for publication.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:Participants provided informed consent to the use of app data for research purposes and agreed to privacy policies and terms of use. This research study was approved by the Partners Human Research Committee IRB 2020P000909 Kings College London Ethics Committee REMAS ID 18210 Review Reference LRS-19/20-18210 and the central ethics committee in Sweden DNR 2020-01803All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesData collected in the app is being shared with other health researchers through the NHS-funded Health Data Research U.K. (HDRUK)/SAIL consortium, housed in the U.K. Secure Research Platform (UKSeRP) in Swansea. Anonymized data is available to be shared with bonafide researchers HDRUK according to their protocols (https://healthdatagateway.org/detail/9b604483-9cdc-41b2-b82c-14ee3dd705f6). U.S. investigators are encouraged to coordinate data requests through the COPE Consortium (www.monganinstitute.org/cope-consortium). Data updates can be found on https://covid.joinzoe.com.
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| 9. |
- Lee, Karla A., et al.
(författare)
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Cancer and Risk of COVID-19 Through a General Community Survey
- 2021
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Ingår i: The Oncologist. - : Oxford University Press (OUP). - 1083-7159 .- 1549-490X. ; 26:1
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Tidskriftsartikel (refereegranskat)abstract
- Individuals with cancer may be at high risk for coronavirus disease 2019 (COVID-19) and adverse outcomes. However, evidence from large population-based studies examining whether cancer and cancer-related therapy exacerbates the risk of COVID-19 infection is still limited. Data were collected from the COVID Symptom Study smartphone application since March 29 through May 8, 2020. Among 23,266 participants with cancer and 1,784,293 without cancer, we documented 10,404 reports of a positive COVID-19 test. Compared with participants without cancer, those living with cancer had a 60% increased risk of a positive COVID-19 test. Among patients with cancer, current treatment with chemotherapy or immunotherapy was associated with a 2.2-fold increased risk of a positive test. The association between cancer and COVID-19 infection was stronger among participants >65 years and males. Future studies are needed to identify subgroups by tumor types and treatment regimens who are particularly at risk for COVID-19 infection and adverse outcomes.
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| 10. |
- Lorenzini, Luigi, et al.
(författare)
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The Open-Access European Prevention of Alzheimer?s Dementia (EPAD) MRI dataset and processing workflow
- 2022
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Ingår i: NeuroImage. - : Elsevier. - 2213-1582. ; 35
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Tidskriftsartikel (refereegranskat)abstract
- The European Prevention of Alzheimer Dementia (EPAD) is a multi-center study that aims to characterize the preclinical and prodromal stages of Alzheimer's Disease. The EPAD imaging dataset includes core (3D T1w, 3D FLAIR) and advanced (ASL, diffusion MRI, and resting-state fMRI) MRI sequences. Here, we give an overview of the semi-automatic multimodal and multisite pipeline that we developed to curate, preprocess, quality control (QC), and compute image-derived phenotypes (IDPs) from the EPAD MRI dataset. This pipeline harmonizes DICOM data structure across sites and performs standardized MRI pre-processing steps. A semi-automated MRI QC procedure was implemented to visualize and flag MRI images next to site-specific distributions of QC features - i.e. metrics that represent image quality. The value of each of these QC features was evaluated through comparison with visual assessment and step-wise parameter selection based on logistic regression. IDPs were computed from 5 different MRI modalities and their sanity and potential clinical relevance were ascertained by assessing their relationship with biological markers of aging and dementia. The EPAD v1500.0 data release encompassed core structural scans from 1356 participants 842 fMRI, 831 dMRI, and 858 ASL scans. From 1356 3D T1w images, we identified 17 images with poor quality and 61 with moderate quality. Five QC features - Signal to Noise Ratio (SNR), Contrast to Noise Ratio (CNR), Coefficient of Joint Variation (CJV), Foreground-Background energy Ratio (FBER), and Image Quality Rate (IQR) - were selected as the most informative on image quality by comparison with visual assessment. The multimodal IDPs showed greater impairment in associations with age and dementia biomarkers, demonstrating the potential of the dataset for future clinical analyses
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| 12. |
- Coenen, Mirthe, et al.
(författare)
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Spatial distributions of white matter hyperintensities on brain MRI: A pooled analysis of individual participant data from 11 memory clinic cohorts
- 2023
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Ingår i: NeuroImage. Clinical. - 2213-1582. ; 40
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The spatial distribution of white matter hyperintensities (WMH) on MRI is often considered in the diagnostic evaluation of patients with cognitive problems. In some patients, clinicians may classify WMH patterns as "unusual", but this is largely based on expert opinion, because detailed quantitative information about WMH distribution frequencies in a memory clinic setting is lacking. Here we report voxel wise 3D WMH distribution frequencies in a large multicenter dataset and also aimed to identify individuals with unusual WMH patterns. METHODS: Individual participant data (N=3525, including 777 participants with subjective cognitive decline, 1389 participants with mild cognitive impairment and 1359 patients with dementia) from eleven memory clinic cohorts, recruited through the Meta VCI Map Consortium, were used. WMH segmentations were provided by participating centers or performed in Utrecht and registered to the Montreal Neurological Institute (MNI)-152 brain template for spatial normalization. To determine WMH distribution frequencies, we calculated WMH probability maps at voxel level. To identify individuals with unusual WMH patterns, region-of-interest (ROI) based WMH probability maps, rule-based scores, and a machine learning method (Local Outlier Factor (LOF)), were implemented. RESULTS: WMH occurred in 82% of voxels from the white matter template with large variation between subjects. Only a small proportion of the white matter (1.7%), mainly in the periventricular areas, was affected by WMH in at least 20% of participants. A large portion of the total white matter was affected infrequently. Nevertheless, 93.8% of individual participants had lesions in voxels that were affected in less than 2% of the population, mainly located in subcortical areas. Only the machine learning method effectively identified individuals with unusual patterns, in particular subjects with asymmetric WMH distribution or with WMH at relatively rarely affected locations despite common locations not being affected. DISCUSSION: Aggregating data from several memory clinic cohorts, we provide a detailed 3D map of WMH lesion distribution frequencies, that informs on common as well as rare localizations. The use of data-driven analysis with LOF can be used to identify unusual patterns, which might serve as an alert that rare causes of WMH should be considered.
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| 13. |
- Cung, T. -T., et al.
(författare)
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Cyclosporine before PCI in Patients with Acute Myocardial Infarction
- 2015
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 373:11, s. 1021-1031
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Experimental and clinical evidence suggests that cyclosporine may attenuate reperfusion injury and reduce myocardial infarct size. We aimed to test whether cyclosporine would improve clinical outcomes and prevent adverse left ventricular remodeling. METHODS In a multicenter, double-blind, randomized trial, we assigned 970 patients with an acute anterior ST-segment elevation myocardial infarction (STEMI) who were undergoing percutaneous coronary intervention (PCI) within 12 hours after symptom onset and who had complete occlusion of the culprit coronary artery to receive a bolus injection of cyclosporine (administered intravenously at a dose of 2.5 mg per kilogram of body weight) or matching placebo before coronary recanalization. The primary outcome was a composite of death from any cause, worsening of heart failure during the initial hospitalization, rehospitalization for heart failure, or adverse left ventricular remodeling at 1 year. Adverse left ventricular remodeling was defined as an increase of 15% or more in the left ventricular end-diastolic volume. RESULTS A total of 395 patients in the cyclosporine group and 396 in the placebo group received the assigned study drug and had data that could be evaluated for the primary outcome at 1 year. The rate of the primary outcome was 59.0% in the cyclosporine group and 58.1% in the control group (odds ratio, 1.04; 95% confidence interval, 0.78 to 1.39; P = 0.77). Cyclosporine did not reduce the incidence of the separate clinical components of the primary outcome or other events, including recurrent infarction, unstable angina, and stroke. No significant difference in the safety profile was observed between the two treatment groups. CONCLUSIONS In patients with anterior STEMI who had been referred for primary PCI, intravenous cyclosporine did not result in better clinical outcomes than those with placebo and did not prevent adverse left ventricular remodeling at 1 year. (Funded by the French Ministry of Health and NeuroVive Pharmaceutical; CIRCUS ClinicalTrials.gov number, NCT01502774; EudraCT number, 2009-013713-99.)
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| 14. |
- James, Sarah-Naomi, et al.
(författare)
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A population-based study of head injury, cognitive function and pathological markers.
- 2021
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Ingår i: Annals of clinical and translational neurology. - : Wiley. - 2328-9503. ; 8:4, s. 842-856
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Tidskriftsartikel (refereegranskat)abstract
- To assess associations between head injury (HI) with loss of consciousness (LOC), ageing and markers of later-life cerebral pathology; and to explore whether those effects may help explain subtle cognitive deficits in dementia-free individuals.Participants (n=502, age=69-71) from the 1946 British Birth Cohort underwent cognitive testing (subtests of Preclinical Alzheimer Cognitive Composite), 18 F-florbetapir Aβ-PET and MR imaging. Measures include Aβ-PET status, brain, hippocampal and white matter hyperintensity (WMH) volumes, normal appearing white matter (NAWM) microstructure, Alzheimer's disease (AD)-related cortical thickness, and serum neurofilament light chain (NFL). LOC HI metrics include HI occurring: (i) >15years prior to the scan (ii) anytime up to age 71.Compared to those with no evidence of an LOC HI, only those reporting an LOC HI>15years prior (16%, n=80) performed worse on cognitive tests at age 69-71, taking into account premorbid cognition, particularly on the digit-symbol substitution test (DSST). Smaller brain volume (BV) and adverse NAWM microstructural integrity explained 30% and 16% of the relationship between HI and DSST, respectively. We found no evidence that LOC HI was associated with Aβ load, hippocampal volume, WMH volume, AD-related cortical thickness or NFL (all p>0.01).Having a LOC HI aged 50's and younger was linked with lower later-life cognitive function at age ~70 than expected. This may reflect a damaging but small impact of HI; explained in part by smaller BV and different microstructure pathways but not via pathology related to AD (amyloid, hippocampal volume, AD cortical thickness) or ongoing neurodegeneration (serum NFL).
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| 15. |
- Kennedy, Beatrice, 1982-, et al.
(författare)
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App-based COVID-19 syndromic surveillance and prediction of hospital admissions in COVID Symptom Study Sweden
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- The app-based COVID Symptom Study was launched in Sweden in April 2020 to contribute to real-time COVID-19 surveillance. We enrolled 143,531 study participants (≥18 years) who contributed 10.6 million daily symptom reports between April 29, 2020 and February 10, 2021. Here, we include data from 19,161 self-reported PCR tests to create a symptom-based model to estimate the individual probability of symptomatic COVID-19, with an AUC of 0.78 (95% CI 0.74-0.83) in an external dataset. These individual probabilities are employed to estimate daily regional COVID-19 prevalence, which are in turn used together with current hospital data to predict next week COVID-19 hospital admissions. We show that this hospital prediction model demonstrates a lower median absolute percentage error (MdAPE: 25.9%) across the five most populated regions in Sweden during the first pandemic wave than a model based on case notifications (MdAPE: 30.3%). During the second wave, the error rates are similar. When we apply the same model to an English dataset, not including local COVID-19 test data, we observe MdAPEs of 22.3% and 19.0% during the first and second pandemic waves, respectively, highlighting the transferability of the prediction model.
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| 16. |
- Louca, Panayiotis, et al.
(författare)
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Modest effects of dietary supplements during the COVID-19 pandemic : Insights from 445 850 users of the COVID-19 Symptom Study app
- 2021
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Ingår i: BMJ Nutrition, Prevention and Health. - : BMJ. - 2516-5542. ; 4:1, s. 149-157
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Dietary supplements may ameliorate SARS-CoV-2 infection, although scientific evidence to support such a role is lacking. We investigated whether users of the COVID-19 Symptom Study app who regularly took dietary supplements were less likely to test positive for SARS-CoV-2 infection. Design App-based community survey. Setting 445 850 subscribers of an app that was launched to enable self-reported information related to SARS-CoV-2 infection for use in the general population in the UK (n=372 720), the USA (n=45 757) and Sweden (n=27 373). Main exposure Self-reported regular dietary supplement usage (constant use during previous 3 months) in the first waves of the pandemic up to 31 July 2020. Main outcome measures SARS-CoV-2 infection confirmed by viral RNA reverse transcriptase PCR test or serology test before 31 July 2020. Results In 372 720 UK participants (175 652 supplement users and 197 068 non-users), those taking probiotics, omega-3 fatty acids, multivitamins or vitamin D had a lower risk of SARS-CoV-2 infection by 14% (95% CI (8% to 19%)), 12% (95% CI (8% to 16%)), 13% (95% CI (10% to 16%)) and 9% (95% CI (6% to 12%)), respectively, after adjusting for potential confounders. No effect was observed for those taking vitamin C, zinc or garlic supplements. On stratification by sex, age and body mass index (BMI), the protective associations in individuals taking probiotics, omega-3 fatty acids, multivitamins and vitamin D were observed in females across all ages and BMI groups, but were not seen in men. The same overall pattern of association was observed in both the US and Swedish cohorts. Conclusion In women, we observed a modest but significant association between use of probiotics, omega-3 fatty acid, multivitamin or vitamin D supplements and lower risk of testing positive for SARS-CoV-2. We found no clear benefits for men nor any effect of vitamin C, garlic or zinc. Randomised controlled trials are required to confirm these observational findings before any therapeutic recommendations can be made.
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| 17. |
- Mazidi, Mohsen, et al.
(författare)
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Diet and lifestyle behaviour disruption related to the pandemic was varied and bidirectional among US and UK adults participating in the ZOE COVID Study
- 2021
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Ingår i: Nature Food. - : Springer Science and Business Media LLC. - 2662-1355. ; 2:12, s. 957-969
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Tidskriftsartikel (refereegranskat)abstract
- Evidence of the impact of the COVID-19 pandemic on health behaviours in the general population is limited. In this retrospective longitudinal study including UK and US participants, we collected diet and lifestyle data pre-pandemic (896,286) and peri-pandemic (291,871) using a mobile health app, and we computed a bidirectional health behaviour disruption index. Disruption of health behaviour was higher in younger, female and socio-economically deprived participants. Loss in body weight was greater in highly disrupted individuals than in those with low disruption. There were large inter-individual changes observed in 46 health and diet behaviours measured peri-pandemic compared with pre-pandemic, but no mean change in the total population. Individuals most adherent to less healthy pre-pandemic health behaviours improved their diet quality and weight compared with those reporting healthier pre-pandemic behaviours, irrespective of relative deprivation; therefore, for a proportion of the population, the pandemic may have provided an impetus to improve health behaviours. Public policies to tackle health inequalities widened by the pandemic should continue to prioritize diet and physical activity for all, as well as more targeted approaches to support younger females and those living in economically deprived areas.
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| 18. |
- Merino, Jordi, et al.
(författare)
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Diet quality and risk and severity of COVID-19 : a prospective cohort study
- 2021
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 70:11, s. 2096-2104
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Poor metabolic health and unhealthy lifestyle factors have been associated with risk and severity of COVID-19, but data for diet are lacking. We aimed to investigate the association of diet quality with risk and severity of COVID-19 and its interaction with socioeconomic deprivation. DESIGN: We used data from 592 571 participants of the smartphone-based COVID-19 Symptom Study. Diet information was collected for the prepandemic period using a short food frequency questionnaire, and diet quality was assessed using a healthful Plant-Based Diet Score, which emphasises healthy plant foods such as fruits or vegetables. Multivariable Cox models were fitted to calculate HRs and 95% CIs for COVID-19 risk and severity defined using a validated symptom-based algorithm or hospitalisation with oxygen support, respectively. RESULTS: Over 3 886 274 person-months of follow-up, 31 815 COVID-19 cases were documented. Compared with individuals in the lowest quartile of the diet score, high diet quality was associated with lower risk of COVID-19 (HR 0.91; 95% CI 0.88 to 0.94) and severe COVID-19 (HR 0.59; 95% CI 0.47 to 0.74). The joint association of low diet quality and increased deprivation on COVID-19 risk was higher than the sum of the risk associated with each factor alone (Pinteraction=0.005). The corresponding absolute excess rate per 10 000 person/months for lowest vs highest quartile of diet score was 22.5 (95% CI 18.8 to 26.3) among persons living in areas with low deprivation and 40.8 (95% CI 31.7 to 49.8) among persons living in areas with high deprivation. CONCLUSIONS: A diet characterised by healthy plant-based foods was associated with lower risk and severity of COVID-19. This association may be particularly evident among individuals living in areas with higher socioeconomic deprivation.
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| 19. |
- Molteni, Erika, et al.
(författare)
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SARS-CoV-2 (COVID-19) infection in pregnant women : characterization of symptoms and syndromes predictive of disease and severity through real-time, remote participatory epidemiology
- 2020
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- BACKGROUND: From the beginning of COVID-19 pandemic, pregnant women have been considered at greater risk of severe morbidity and mortality. However, data on hospitalized pregnant women show that the symptom profile and risk factors for severe disease are similar to those among women who are not pregnant, although preterm birth, Cesarean delivery, and stillbirth may be more frequent and vertical transmission is possible. Limited data are available for the cohort of pregnant women that gave rise to these hospitalized cases, hindering our ability to quantify risk of COVID-19 sequelae for pregnant women in the community.OBJECTIVE: To test the hypothesis that pregnant women in community differ in their COVID-19 symptoms profile and disease severity compared to non-pregnant women. This was assessed in two community-based cohorts of women aged 18-44 years in the United Kingdom, Sweden and the United States of America.STUDY DESIGN: This observational study used prospectively collected longitudinal (smartphone application interface) and cross-sectional (web-based survey) data. Participants in the discovery cohort were drawn from 400,750 UK, Sweden and US women (79 pregnant who tested positive) who self-reported symptoms and events longitudinally via their smartphone, and a replication cohort drawn from 1,344,966 USA women (162 pregnant who tested positive) cross-sectional self-reports samples from the social media active user base. The study compared frequencies of symptoms and events, including self-reported SARS-CoV-2 testing and differences between pregnant and non-pregnant women who were hospitalized and those who recovered in the community. Multivariable regression was used to investigate disease severity and comorbidity effects.RESULTS: Pregnant and non-pregnant women positive for SARS-CoV-2 infection drawn from these community cohorts were not different with respect to COVID-19-related severity. Pregnant women were more likely to have received SARS-CoV-2 testing than non-pregnant, despite reporting fewer clinical symptoms. Pre-existing lung disease was most closely associated with the severity of symptoms in pregnant hospitalized women. Heart and kidney diseases and diabetes were additional factors of increased risk. The most frequent symptoms among all non-hospitalized women were anosmia [63% in pregnant, 92% in non-pregnant] and headache [72%, 62%]. Cardiopulmonary symptoms, including persistent cough [80%] and chest pain [73%], were more frequent among pregnant women who were hospitalized. Gastrointestinal symptoms, including nausea and vomiting, were different among pregnant and non-pregnant women who developed severe outcomes.CONCLUSIONS: Although pregnancy is widely considered a risk factor for SARS-CoV-2 infection and outcomes, and was associated with higher propensity for testing, the profile of symptom characteristics and severity in our community-based cohorts were comparable to those observed among non-pregnant women, except for the gastrointestinal symptoms. Consistent with observations in non-pregnant populations, comorbidities such as lung disease and diabetes were associated with an increased risk of more severe SARS-CoV-2 infection during pregnancy. Pregnant women with pre-existing conditions require careful monitoring for the evolution of their symptoms during SARS-CoV-2 infection.
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| 20. |
- Molteni, Erika, et al.
(författare)
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Symptoms and syndromes associated with SARS-CoV-2 infection and severity in pregnant women from two community cohorts
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- We tested whether pregnant and non-pregnant women differ in COVID-19 symptom profile and severity, and we extended previous investigations on hospitalized pregnant women to those who did not require hospitalization. Two female community-based cohorts (18–44 years) provided longitudinal (smartphone application, N = 1,170,315, n = 79 pregnant tested positive) and cross-sectional (web-based survey, N = 1,344,966, n = 134 pregnant tested positive) data, prospectively collected through self-participatory citizen surveillance in UK, Sweden and USA. Pregnant and non-pregnant were compared for frequencies of events, including SARS-CoV-2 testing, symptoms and hospitalization rates. Multivariable regression was used to investigate symptoms severity and comorbidity effects. Pregnant and non-pregnant women positive for SARS-CoV-2 infection were not different in syndromic severity, except for gastrointestinal symptoms. Pregnant were more likely to have received testing, despite reporting fewer symptoms. Pre-existing lung disease was most closely associated with syndromic severity in pregnant hospitalized. Heart and kidney diseases and diabetes increased risk. The most frequent symptoms among non-hospitalized women were anosmia [63% pregnant, 92% non-pregnant] and headache [72%, 62%]. Cardiopulmonary symptoms, including persistent cough [80%] and chest pain [73%], were more frequent among pregnant who were hospitalized. Consistent with observations in non-pregnant populations, lung disease and diabetes were associated with increased risk of more severe SARS-CoV-2 infection during pregnancy.
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| 21. |
- Nguyen, Long H., et al.
(författare)
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Self-reported COVID-19 vaccine hesitancy and uptake among participants from different racial and ethnic groups in the United States and United Kingdom
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Worldwide, racial and ethnic minorities have been disproportionately impacted by COVID-19 with increased risk of infection, its related complications, and death. In the initial phase of population-based vaccination in the United States (U.S.) and United Kingdom (U.K.), vaccine hesitancy may result in differences in uptake. We performed a cohort study among U.S. and U.K. participants who volunteered to take part in the smartphone-based COVID Symptom Study (March 2020-February 2021) and used logistic regression to estimate odds ratios of vaccine hesitancy and uptake. In the U.S. (n = 87,388), compared to white participants, vaccine hesitancy was greater for Black and Hispanic participants and those reporting more than one or other race. In the U.K. (n = 1,254,294), racial and ethnic minority participants showed similar levels of vaccine hesitancy to the U.S. However, associations between participant race and ethnicity and levels of vaccine uptake were observed to be different in the U.S. and the U.K. studies. Among U.S. participants, vaccine uptake was significantly lower among Black participants, which persisted among participants that self-reported being vaccine-willing. In contrast, statistically significant racial and ethnic disparities in vaccine uptake were not observed in the U.K sample. In this study of self-reported vaccine hesitancy and uptake, lower levels of vaccine uptake in Black participants in the U.S. during the initial vaccine rollout may be attributable to both hesitancy and disparities in access.
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| 22. |
- Singleton, Ellen H., et al.
(författare)
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Investigating the clinico-anatomical dissociation in the behavioral variant of Alzheimer disease
- 2020
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Ingår i: Alzheimer's Research and Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: We previously found temporoparietal-predominant atrophy patterns in the behavioral variant of Alzheimer’s disease (bvAD), with relative sparing of frontal regions. Here, we aimed to understand the clinico-anatomical dissociation in bvAD based on alternative neuroimaging markers. Methods: We retrospectively included 150 participants, including 29 bvAD, 28 “typical” amnestic-predominant AD (tAD), 28 behavioral variant of frontotemporal dementia (bvFTD), and 65 cognitively normal participants. Patients with bvAD were compared with other diagnostic groups on glucose metabolism and metabolic connectivity measured by [18F]FDG-PET, and on subcortical gray matter and white matter hyperintensity (WMH) volumes measured by MRI. A receiver-operating-characteristic-analysis was performed to determine the neuroimaging measures with highest diagnostic accuracy. Results: bvAD and tAD showed predominant temporoparietal hypometabolism compared to controls, and did not differ in direct contrasts. However, overlaying statistical maps from contrasts between patients and controls revealed broader frontoinsular hypometabolism in bvAD than tAD, partially overlapping with bvFTD. bvAD showed greater anterior default mode network (DMN) involvement than tAD, mimicking bvFTD, and reduced connectivity of the posterior cingulate cortex with prefrontal regions. Analyses of WMH and subcortical volume showed closer resemblance of bvAD to tAD than to bvFTD, and larger amygdalar volumes in bvAD than tAD respectively. The top-3 discriminators for bvAD vs. bvFTD were FDG posterior-DMN-ratios (bvADbvFTD, area under the curve [AUC] range 0.85–0.91, all p < 0.001). The top-3 for bvAD vs. tAD were amygdalar volume (bvAD>tAD), MRI anterior-DMN-ratios (bvAD
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| 23. |
- Sudre, Carole H., et al.
(författare)
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Attributes and predictors of long COVID
- 2021
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Ingår i: Nature Medicine. - : Springer Nature. - 1078-8956 .- 1546-170X. ; 27:4, s. 626-631
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Tidskriftsartikel (refereegranskat)abstract
- Reports of long-lasting coronavirus disease 2019 (COVID-19) symptoms, the so-called ‘long COVID’, are rising but little is known about prevalence, risk factors or whether it is possible to predict a protracted course early in the disease. We ana- lyzed data from 4,182 incident cases of COVID-19 in which individuals self-reported their symptoms prospectively in the COVID Symptom Study app1. A total of 558 (13.3%) partici- pants reported symptoms lasting ≥28 days, 189 (4.5%) for ≥8 weeks and 95 (2.3%) for ≥12 weeks. Long COVID was characterized by symptoms of fatigue, headache, dyspnea and anosmia and was more likely with increasing age and body mass index and female sex. Experiencing more than five symptoms during the first week of illness was associated with long COVID (odds ratio = 3.53 (2.76–4.50)). A simple model to distinguish between short COVID and long COVID at 7 days (total sample size, n = 2,149) showed an area under the curve of the receiver operating characteristic curve of 76%, with replication in an independent sample of 2,472 individuals who were positive for severe acute respiratory syndrome coronavi- rus 2. This model could be used to identify individuals at risk of long COVID for trials of prevention or treatment and to plan education and rehabilitation services.
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| 24. |
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| 25. |
- Varsavsky, Thomas, et al.
(författare)
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Detecting COVID-19 infection hotspots in England using large-scale self-reported data from a mobile application : a prospective, observational study
- 2021
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Ingår i: The Lancet Public Health. - : Elsevier. - 2468-2667. ; 6:1, s. 21-29
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Tidskriftsartikel (refereegranskat)abstract
- Background: As many countries seek to slow the spread of COVID-19 without reimposing national restrictions, it has become important to track the disease at a local level to identify areas in need of targeted intervention. Methods: In this prospective, observational study, we did modelling using longitudinal, self-reported data from users of the COVID Symptom Study app in England between March 24, and Sept 29, 2020. Beginning on April 28, in England, the Department of Health and Social Care allocated RT-PCR tests for COVID-19 to app users who logged themselves as healthy at least once in 9 days and then reported any symptom. We calculated incidence of COVID-19 using the invited swab (RT-PCR) tests reported in the app, and we estimated prevalence using a symptom-based method (using logistic regression) and a method based on both symptoms and swab test results. We used incidence rates to estimate the effective reproduction number, R(t), modelling the system as a Poisson process and using Markov Chain Monte-Carlo. We used three datasets to validate our models: the Office for National Statistics (ONS) Community Infection Survey, the Real-time Assessment of Community Transmission (REACT-1) study, and UK Government testing data. We used geographically granular estimates to highlight regions with rapidly increasing case numbers, or hotspots. Findings: From March 24 to Sept 29, 2020, a total of 2 873 726 users living in England signed up to use the app, of whom 2 842 732 (98·9%) provided valid age information and daily assessments. These users provided a total of 120 192 306 daily reports of their symptoms, and recorded the results of 169 682 invited swab tests. On a national level, our estimates of incidence and prevalence showed a similar sensitivity to changes to those reported in the ONS and REACT-1 studies. On Sept 28, 2020, we estimated an incidence of 15 841 (95% CI 14 023–17 885) daily cases, a prevalence of 0·53% (0·45–0·60), and R(t) of 1·17 (1·15–1·19) in England. On a geographically granular level, on Sept 28, 2020, we detected 15 (75%) of the 20 regions with highest incidence according to government test data. Interpretation: Our method could help to detect rapid case increases in regions where government testing provision is lower. Self-reported data from mobile applications can provide an agile resource to inform policy makers during a quickly moving pandemic, serving as a complementary resource to more traditional instruments for disease surveillance. Funding: Zoe Global, UK Government Department of Health and Social Care, Wellcome Trust, UK Engineering and Physical Sciences Research Council, UK National Institute for Health Research, UK Medical Research Council and British Heart Foundation, Alzheimer's Society, Chronic Disease Research Foundation.
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| 26. |
- Wagen, Aaron Z, et al.
(författare)
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Life course, genetic, and neuropathological associations with brain age in the 1946 British Birth Cohort: a population-based study.
- 2022
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Ingår i: The Lancet. Healthy longevity. - 2666-7568. ; 3:9
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Tidskriftsartikel (refereegranskat)abstract
- A neuroimaging-based biomarker termed the brain age is thought to reflect variability in the brain's ageing process and predict longevity. Using Insight 46, a unique narrow-age birth cohort, we aimed to examine potential drivers and correlates of brain age.Participants, born in a single week in 1946 in mainland Britain, have had 24 prospective waves of data collection to date, including MRI and amyloid PET imaging at approximately 70 years old. Using MRI data from a previously defined selection of this cohort, we derived brain-predicted age from an established machine-learning model (trained on 2001 healthy adults aged 18-90 years); subtracting this from chronological age (at time of assessment) gave the brain-predicted age difference (brain-PAD). We tested associations with data from early life, midlife, and late life, as well as rates of MRI-derived brain atrophy.Between May 28, 2015, and Jan 10, 2018, 502 individuals were assessed as part of Insight 46. We included 456 participants (225 female), with a mean chronological age of 70·7 years (SD 0·7; range 69·2 to 71·9). The mean brain-predicted age was 67·9 years (8·2, 46·3 to 94·3). Female sex was associated with a 5·4-year (95% CI 4·1 to 6·8) younger brain-PAD than male sex. An increase in brain-PAD was associated with increased cardiovascular risk at age 36 years (β=2·3 [95% CI 1·5 to 3·0]) and 69 years (β=2·6 [1·9 to 3·3]); increased cerebrovascular disease burden (1·9 [1·3 to 2·6]); lower cognitive performance (-1·3 [-2·4 to -0·2]); and increased serum neurofilament light concentration (1·2 [0·6 to 1·9]). Higher brain-PAD was associated with future hippocampal atrophy over the subsequent 2 years (0·003 mL/year [0·000 to 0·006] per 5-year increment in brain-PAD). Early-life factors did not relate to brain-PAD. Combining 12 metrics in a hierarchical partitioning model explained 33% of the variance in brain-PAD.Brain-PAD was associated with cardiovascular risk, and imaging and biochemical markers of neurodegeneration. These findings support brain-PAD as an integrative summary metric of brain health, reflecting multiple contributions to pathological brain ageing, and which might have prognostic utility.Alzheimer's Research UK, Medical Research Council Dementia Platforms UK, Selfridges Group Foundation, Wolfson Foundation, Wellcome Trust, Brain Research UK, Alzheimer's Association.
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