| 1. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 2. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
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| 4. |
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| 5. |
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| 6. |
- Morales, J. C., et al.
(författare)
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A giant exoplanet orbiting a very-low-mass star challenges planet formation models
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 365:6460, s. 1441-1445
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Tidskriftsartikel (refereegranskat)abstract
- Surveys have shown that super-Earth and Neptune-mass exoplanets are more frequent than gas giants around low-mass stars, as predicted by the core accretion theory of planet formation. We report the discovery of a giant planet around the very-low-mass star GJ 3512, as determined by optical and near-infrared radial-velocity observations. The planet has a minimum mass of 0.46 Jupiter masses, very high for such a small host star, and an eccentric 204-day orbit. Dynamical models show that the high eccentricity is most likely due to planet-planet interactions. We use simulations to demonstrate that the GJ 3512 planetary system challenges generally accepted formation theories, and that it puts constraints on the planet accretion and migration rates. Disk instabilities may be more efficient in forming planets than previously thought.
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| 7. |
- Lane, J. C. E., et al.
(författare)
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Risk of hydroxychloroquine alone and in combination with azithromycin in the treatment of rheumatoid arthritis: a multinational, retrospective study
- 2020
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Ingår i: Lancet Rheumatology. - : Elsevier BV. - 2665-9913. ; 2:11
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Tidskriftsartikel (refereegranskat)abstract
- Background Hydroxychloroquine, a drug commonly used in the treatment of rheumatoid arthritis, has received much negative publicity for adverse events associated with its authorisation for emergency use to treat patients with COVID-19 pneumonia. We studied the safety of hydroxychloroquine, alone and in combination with azithromycin, to determine the risk associated with its use in routine care in patients with rheumatoid arthritis. Methods In this multinational, retrospective study, new user cohort studies in patients with rheumatoid arthritis aged 18 years or older and initiating hydroxychloroquine were compared with those initiating sulfasalazine and followed up over 30 days, with 16 severe adverse events studied. Self-controlled case series were done to further establish safety in wider populations, and included all users of hydroxychloroquine regardless of rheumatoid arthritis status or indication. Separately, severe adverse events associated with hydroxychloroquine plus azithromycin (compared with hydroxychloroquine plus amoxicillin) were studied. Data comprised 14 sources of claims data or electronic medical records from Germany, Japan, the Netherlands, Spain, the UK, and the USA. Propensity score stratification and calibration using negative control outcomes were used to address confounding. Cox models were fitted to estimate calibrated hazard ratios (HRs) according to drug use. Estimates were pooled where the I-2 value was less than 0.4. Findings The study included 956 374 users of hydroxychloroquine, 310 350 users of sulfasalazine, 323 122 users of hydroxychloroquine plus azithromycin, and 351 956 users of hydroxychloroquine plus amoxicillin. No excess risk of severe adverse events was identified when 30-day hydroxychloroquine and sulfasalazine use were compared. Selfcontrolled case series confirmed these findings. However, long-term use of hydroxychloroquine appeared to be associated with increased cardiovascular mortality (calibrated HR 1.65 [95% CI 1.12-2.44]). Addition of azithromycin appeared to be associated with an increased risk of 30-day cardiovascular mortality (calibrated HR 2.19 [95% CI 1.22-3.95]), chest pain or angina (1.15 [1.05-1.26]), and heart failure (1.22 [1.02-1.45]). Interpretation Hydroxychloroquine treatment appears to have no increased risk in the short term among patients with rheumatoid arthritis, but in the long term it appears to be associated with excess cardiovascular mortality. The addition of azithromycin increases the risk of heart failure and cardiovascular mortality even in the short term. We call for careful consideration of the benefit-risk trade-off when counselling those on hydroxychloroquine treatment. Copyright (c) 2020 The Author(s). Published by Elsevier Ltd.
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| 8. |
- Burn, E., et al.
(författare)
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Deep phenotyping of 34,128 adult patients hospitalised with COVID-19 in an international network study
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Comorbid conditions appear to be common among individuals hospitalised with coronavirus disease 2019 (COVID-19) but estimates of prevalence vary and little is known about the prior medication use of patients. Here, we describe the characteristics of adults hospitalised with COVID-19 and compare them with influenza patients. We include 34,128 (US: 8362, South Korea: 7341, Spain: 18,425) COVID-19 patients, summarising between 4811 and 11,643 unique aggregate characteristics. COVID-19 patients have been majority male in the US and Spain, but predominantly female in South Korea. Age profiles vary across data sources. Compared to 84,585 individuals hospitalised with influenza in 2014-19, COVID-19 patients have more typically been male, younger, and with fewer comorbidities and lower medication use. While protecting groups vulnerable to influenza is likely a useful starting point in the response to COVID-19, strategies will likely need to be broadened to reflect the particular characteristics of individuals being hospitalised with COVID-19. Detailed knowledge of the characteristics of COVID-19 patients helps with public health planning. Here, the authors use routinely-collected data from seven databases in three countries to describe the characteristics of >30,000 patients admitted with COVID-19 and compare them with those admitted for influenza in previous years.
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| 9. |
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| 10. |
- Filipe, A., et al.
(författare)
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White Book on Physical and Rehabilitation Medicine in Europe Introductions, Executive Summary, and Methodology
- 2018
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Ingår i: European Journal of Physical and Rehabilitation Medicine. - : Edizioni Minerva Medica. - 1973-9087 .- 1973-9095. ; 54:2, s. 125-155
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Tidskriftsartikel (refereegranskat)abstract
- The White Book (WB) of Physical and Rehabilitation Medicine (PRM) in Europe is produced by the 4 European PRM Bodies (European Academy of Rehabilitation Medicine - EARM, European Society of PRM - ESPRM, European Union of Medical Specialists - PRM Section, European College of PRM-ECPRM served by the European Union of Medical Specialists-PRM Board) and constitutes the reference book for PRM physicians in Europe. It has now reached its third edition; the first was published in 1989 and the second in 2006/2007. The WB has multiple purposes, including providing a unifying framework for European countries, to inform decision-makers on European and national level, to offer educational material for PRM trainees and physicians and information about PRM to the medical community, other rehabilitation professionals and the public. The WB states the importance of PRM, a primary medical specialty that is present all over Europe, with a specific corpus disciplinae, a common background and history throughout Europe. PRM is internationally recognized and a partner of major international bodies, including the World Health Organization (WHO). PRM activities are strongly based on the documents of the United Nations (UN) and WHO, such as the Convention of the Rights of Persons with Disabilities (2006), the World Report on Disability (2011), the WHO Global Disability Action Plan 2014-2021 (2014) and the WHO initiative "Rehabilitation 2030: a call for action" (2017). The WB is organized in 4 sections, 11 chapters and some appendices. The WB starts with basic definitions and concepts of PRM and continues with why rehabilitation is needed by individuals and society. Rehabilitation focuses not only on health conditions but also on functioning. Accordingly. PRM is the medical specialty that strives to improve functioning of people with a health condition or experiencing disability. The fundamentals of PRM, the history of the PRM specialty, and the structure and activities of PRM organizations in Europe are presented, followed by a thorough presentation of the practice of PRM, i.e. knowledge and skills of PRM physicians, the clinical field of competence of PRM, the place of the PRM specialty in the healthcare system and society, education and continuous professional development of PRM physicians, specificities and challenges of science and research in PRM. The WB concludes with the way forward for the specialty: challenges and perspectives for the future of PRM.
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| 11. |
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| 12. |
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| 13. |
- Jabbari, E., et al.
(författare)
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Diagnosis across the Spectrum of Progressive Supranuclear Palsy and Corticobasal Syndrome
- 2020
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 77:3, s. 377-387
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Tidskriftsartikel (refereegranskat)abstract
- Importance Atypical parkinsonian syndromes (APS), including progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and multiple system atrophy (MSA), may be difficult to distinguish in early stages and are often misdiagnosed as Parkinson disease (PD). The diagnostic criteria for PSP have been updated to encompass a range of clinical subtypes but have not been prospectively studied. Objective To define the distinguishing features of PSP and CBS subtypes and to assess their usefulness in facilitating early diagnosis and separation from PD. Design, Setting, Participants This cohort study recruited patients with APS and PD from movement disorder clinics across the United Kingdom from September 1, 2015, through December 1, 2018. Patients with APS were stratified into the following groups: those with Richardson syndrome (PSP-RS), PSP-subcortical (including PSP-parkinsonism and progressive gait freezing subtypes), PSP-cortical (including PSP-frontal and PSP-CBS overlap subtypes), MSA-parkinsonism, MSA-cerebellar, CBS–Alzheimer disease (CBS-AD), and CBS–non-AD. Data were analyzed from February 1, through May 1, 2019. Main Outcomes and Measures Baseline group comparisons used (1) clinical trajectory; (2) cognitive screening scales; (3) serum neurofilament light chain (NF-L) levels; (4) TRIM11, ApoE, and MAPT genotypes; and (5) volumetric magnetic resonance imaging measures. Results A total of 222 patients with APS (101 with PSP, 55 with MSA, 40 with CBS, and 26 indeterminate) were recruited (129 [58.1%] male; mean [SD] age at recruitment, 68.3 [8.7] years). Age-matched control participants (n=76) and patients with PD (n=1967) were included for comparison. Concordance between the antemortem clinical and pathologic diagnoses was achieved in 12 of 13 patients with PSP and CBS (92.3%) undergoing postmortem evaluation. Applying the Movement Disorder Society PSP diagnostic criteria almost doubled the number of patients diagnosed with PSP from 58 to 101. Forty-nine of 101 patients with reclassified PSP (48.5%) did not have the classic PSP-RS subtype. Patients in the PSP-subcortical group had a longer diagnostic latency and a more benign clinical trajectory than those in PSP-RS and PSP-cortical groups. The PSP-subcortical group was distinguished from PSP-cortical and PSP-RS groups by cortical volumetric magnetic resonance imaging measures (area under the curve [AUC], 0.84-0.89), cognitive profile (AUC, 0.80-0.83), serum NF-L level (AUC, 0.75-0.83), and TRIM11 rs564309 genotype. Midbrain atrophy was a common feature of all PSP groups. Eight of 17 patients with CBS (47.1%) undergoing cerebrospinal fluid analysis were identified as having the CBS-AD subtype. Patients in the CBS-AD group had a longer diagnostic latency, relatively benign clinical trajectory, greater cognitive impairment, and higher APOE-ε4 allele frequency than those in the CBS–non-AD group (AUC, 0.80-0.87; P<.05). Serum NF-L levels distinguished PD from all PSP and CBS cases combined (AUC, 0.80; P<.05). Conclusions and Relevance These findings suggest that studies focusing on the PSP-RS subtype are likely to miss a large number of patients with underlying PSP tau pathology. Analysis of cerebrospinal fluid defined a distinct CBS-AD subtype. The PSP and CBS subtypes have distinct characteristics that may enhance their early diagnosis.
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| 14. |
- Dominguez-Valentin, M, et al.
(författare)
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No Difference in Penetrance between Truncating and Missense/Aberrant Splicing Pathogenic Variants in MLH1 and MSH2: A Prospective Lynch Syndrome Database Study
- 2021
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Ingår i: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 10:13
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Tidskriftsartikel (refereegranskat)abstract
- Background. Lynch syndrome is the most common genetic predisposition for hereditary cancer. Carriers of pathogenic changes in mismatch repair (MMR) genes have an increased risk of developing colorectal (CRC), endometrial, ovarian, urinary tract, prostate, and other cancers, depending on which gene is malfunctioning. In Lynch syndrome, differences in cancer incidence (penetrance) according to the gene involved have led to the stratification of cancer surveillance. By contrast, any differences in penetrance determined by the type of pathogenic variant remain unknown. Objective. To determine cumulative incidences of cancer in carriers of truncating and missense or aberrant splicing pathogenic variants of the MLH1 and MSH2 genes. Methods. Carriers of pathogenic variants of MLH1 (path_MLH1) and MSH2 (path_MSH2) genes filed in the Prospective Lynch Syndrome Database (PLSD) were categorized as truncating or missense/aberrant splicing according to the InSiGHT criteria for pathogenicity. Results. Among 5199 carriers, 1045 had missense or aberrant splicing variants, and 3930 had truncating variants. Prospective observation years for the two groups were 8205 and 34,141 years, respectively, after which there were no significant differences in incidences for cancer overall or for colorectal cancer or endometrial cancers separately. Conclusion. Truncating and missense or aberrant splicing pathogenic variants were associated with similar average cumulative incidences of cancer in carriers of path MLH1 and path_MSH2.
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| 15. |
- Chelban, V., et al.
(författare)
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Neurofilament light levels predict clinical progression and death in multiple system atrophy
- 2022
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Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 145:12, s. 4398-4408
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Tidskriftsartikel (refereegranskat)abstract
- In this large multiple system atrophy cohort, Chelban et al. show that plasma NfL correlates with clinical disease severity, progression and prognosis, and could help inform patient stratification and monitor treatment responses in future trials of putative disease-modifying agents. Disease-modifying treatments are currently being trialled in multiple system atrophy. Approaches based solely on clinical measures are challenged by heterogeneity of phenotype and pathogenic complexity. Neurofilament light chain protein has been explored as a reliable biomarker in several neurodegenerative disorders but data on multiple system atrophy have been limited. Therefore, neurofilament light chain is not yet routinely used as an outcome measure in multiple system atrophy. We aimed to comprehensively investigate the role and dynamics of neurofilament light chain in multiple system atrophy combined with cross-sectional and longitudinal clinical and imaging scales and for subject trial selection. In this cohort study, we recruited cross-sectional and longitudinal cases in a multicentre European set-up. Plasma and CSF neurofilament light chain concentrations were measured at baseline from 212 multiple system atrophy cases, annually for a mean period of 2 years in 44 multiple system atrophy patients in conjunction with clinical, neuropsychological and MRI brain assessments. Baseline neurofilament light chain characteristics were compared between groups. Cox regression was used to assess survival; receiver operating characteristic analysis to assess the ability of neurofilament light chain to distinguish between multiple system atrophy patients and healthy controls. Multivariate linear mixed-effects models were used to analyse longitudinal neurofilament light chain changes and correlated with clinical and imaging parameters. Polynomial models were used to determine the differential trajectories of neurofilament light chain in multiple system atrophy. We estimated sample sizes for trials aiming to decrease neurofilament light chain levels. We show that in multiple system atrophy, baseline plasma neurofilament light chain levels were better predictors of clinical progression, survival and degree of brain atrophy than the neurofilament light chain rate of change. Comparative analysis of multiple system atrophy progression over the course of disease, using plasma neurofilament light chain and clinical rating scales, indicated that neurofilament light chain levels rise as the motor symptoms progress, followed by deceleration in advanced stages. Sample size prediction suggested that significantly lower trial participant numbers would be needed to demonstrate treatment effects when incorporating plasma neurofilament light chain values into multiple system atrophy clinical trials in comparison to clinical measures alone. In conclusion, neurofilament light chain correlates with clinical disease severity, progression and prognosis in multiple system atrophy. Combined with clinical and imaging analysis, neurofilament light chain can inform patient stratification and serve as a reliable biomarker of treatment response in future multiple system atrophy trials of putative disease-modifying agents.
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| 16. |
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| 17. |
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| 18. |
- Street, D., et al.
(författare)
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Progression of atypical parkinsonian syndromes: PROSPECT-M-UK study implications for clinical trials
- 2023
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Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 146:8, s. 3232-3242
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Tidskriftsartikel (refereegranskat)abstract
- Street et al. compare candidate clinical trial end points in progressive supranuclear palsy, multiple system atrophy, corticobasal syndrome and related disorders. Neuroimaging metrics generally enable lower sample sizes than cognitive and functional measures, although optimal outcome measures vary by disease and subtype. The advent of clinical trials of disease-modifying agents for neurodegenerative disease highlights the need for evidence-based end point selection. Here we report the longitudinal PROSPECT-M-UK study of progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), multiple system atrophy (MSA) and related disorders, to compare candidate clinical trial end points. In this multicentre UK study, participants were assessed with serial questionnaires, motor examination, neuropsychiatric and MRI assessments at baseline, 6 and 12 months. Participants were classified by diagnosis at baseline and study end, into Richardson syndrome, PSP-subcortical (PSP-parkinsonism and progressive gait freezing subtypes), PSP-cortical (PSP-frontal, PSP-speech and language and PSP-CBS subtypes), MSA-parkinsonism, MSA-cerebellar, CBS with and without evidence of Alzheimer's disease pathology and indeterminate syndromes. We calculated annual rate of change, with linear mixed modelling and sample sizes for clinical trials of disease-modifying agents, according to group and assessment type. Two hundred forty-three people were recruited [117 PSP, 68 CBS, 42 MSA and 16 indeterminate; 138 (56.8%) male; age at recruitment 68.7 +/- 8.61 years]. One hundred and fifty-nine completed the 6-month assessment (82 PSP, 27 CBS, 40 MSA and 10 indeterminate) and 153 completed the 12-month assessment (80 PSP, 29 CBS, 35 MSA and nine indeterminate). Questionnaire, motor examination, neuropsychiatric and neuroimaging measures declined in all groups, with differences in longitudinal change between groups. Neuroimaging metrics would enable lower sample sizes to achieve equivalent power for clinical trials than cognitive and functional measures, often achieving N < 100 required for 1-year two-arm trials (with 80% power to detect 50% slowing). However, optimal outcome measures were disease-specific. In conclusion, phenotypic variance within PSP, CBS and MSA is a major challenge to clinical trial design. Our findings provide an evidence base for selection of clinical trial end points, from potential functional, cognitive, clinical or neuroimaging measures of disease progression.
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| 19. |
- Williams, R. D., et al.
(författare)
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Seek COVER: using a disease proxy to rapidly develop and validate a personalized risk calculator for COVID-19 outcomes in an international network
- 2022
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Ingår i: BMC Medical Research Methodology. - : Springer Science and Business Media LLC. - 1471-2288. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: We investigated whether we could use influenza data to develop prediction models for COVID-19 to increase the speed at which prediction models can reliably be developed and validated early in a pandemic. We developed COVID-19 Estimated Risk (COVER) scores that quantify a patient’s risk of hospital admission with pneumonia (COVER-H), hospitalization with pneumonia requiring intensive services or death (COVER-I), or fatality (COVER-F) in the 30-days following COVID-19 diagnosis using historical data from patients with influenza or flu-like symptoms and tested this in COVID-19 patients. Methods: We analyzed a federated network of electronic medical records and administrative claims data from 14 data sources and 6 countries containing data collected on or before 4/27/2020. We used a 2-step process to develop 3 scores using historical data from patients with influenza or flu-like symptoms any time prior to 2020. The first step was to create a data-driven model using LASSO regularized logistic regression, the covariates of which were used to develop aggregate covariates for the second step where the COVER scores were developed using a smaller set of features. These 3 COVER scores were then externally validated on patients with 1) influenza or flu-like symptoms and 2) confirmed or suspected COVID-19 diagnosis across 5 databases from South Korea, Spain, and the United States. Outcomes included i) hospitalization with pneumonia, ii) hospitalization with pneumonia requiring intensive services or death, and iii) death in the 30 days after index date. Results: Overall, 44,507 COVID-19 patients were included for model validation. We identified 7 predictors (history of cancer, chronic obstructive pulmonary disease, diabetes, heart disease, hypertension, hyperlipidemia, kidney disease) which combined with age and sex discriminated which patients would experience any of our three outcomes. The models achieved good performance in influenza and COVID-19 cohorts. For COVID-19 the AUC ranges were, COVER-H: 0.69–0.81, COVER-I: 0.73–0.91, and COVER-F: 0.72–0.90. Calibration varied across the validations with some of the COVID-19 validations being less well calibrated than the influenza validations. Conclusions: This research demonstrated the utility of using a proxy disease to develop a prediction model. The 3 COVER models with 9-predictors that were developed using influenza data perform well for COVID-19 patients for predicting hospitalization, intensive services, and fatality. The scores showed good discriminatory performance which transferred well to the COVID-19 population. There was some miscalibration in the COVID-19 validations, which is potentially due to the difference in symptom severity between the two diseases. A possible solution for this is to recalibrate the models in each location before use. © 2022, The Author(s).
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| 20. |
- Prats-Uribe, A., et al.
(författare)
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Use of repurposed and adjuvant drugs in hospital patients with covid-19: Multinational network cohort study
- 2021
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Ingår i: The BMJ. - : BMJ. - 0959-8146. ; 373
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Tidskriftsartikel (refereegranskat)abstract
- Objective To investigate the use of repurposed and adjuvant drugs in patients admitted to hospital with covid-19 across three continents. Design Multinational network cohort study. Setting Hospital electronic health records from the United States, Spain, and China, and nationwide claims data from South Korea. Participants 303 264 patients admitted to hospital with covid-19 from January 2020 to December 2020. Main outcome measures Prescriptions or dispensations of any drug on or 30 days after the date of hospital admission for covid-19. Results Of the 303 264 patients included, 290 131 were from the US, 7599 from South Korea, 5230 from Spain, and 304 from China. 3455 drugs were identified. Common repurposed drugs were hydroxychloroquine (used in from <5 (<2%) patients in China to 2165 (85.1%) in Spain), azithromycin (from 15 (4.9%) in China to 1473 (57.9%) in Spain), combined lopinavir and ritonavir (from 156 (<2%) in the VA-OMOP US to 2,652 (34.9%) in South Korea and 1285 (50.5%) in Spain), and umifenovir (0% in the US, South Korea, and Spain and 238 (78.3%) in China). Use of adjunctive drugs varied greatly, with the five most used treatments being enoxaparin, fluoroquinolones, ceftriaxone, vitamin D, and corticosteroids. Hydroxychloroquine use increased rapidly from March to April 2020 but declined steeply in May to June and remained low for the rest of the year. The use of dexamethasone and corticosteroids increased steadily during 2020. Conclusions Multiple drugs were used in the first few months of the covid-19 pandemic, with substantial geographical and temporal variation. Hydroxychloroquine, azithromycin, lopinavir-ritonavir, and umifenovir (in China only) were the most prescribed repurposed drugs. Antithrombotics, antibiotics, H2 receptor antagonists, and corticosteroids were often used as adjunctive treatments. Research is needed on the comparative risk and benefit of these treatments in the management of covid-19. ©
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| 21. |
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| 25. |
- Recalde, M., et al.
(författare)
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Characteristics and outcomes of 627 044 COVID-19 patients living with and without obesity in the United States, Spain, and the United Kingdom
- 2021
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 45:11, s. 2347-2357
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Tidskriftsartikel (refereegranskat)abstract
- Background A detailed characterization of patients with COVID-19 living with obesity has not yet been undertaken. We aimed to describe and compare the demographics, medical conditions, and outcomes of COVID-19 patients living with obesity (PLWO) to those of patients living without obesity. Methods We conducted a cohort study based on outpatient/inpatient care and claims data from January to June 2020 from Spain, the UK, and the US. We used six databases standardized to the OMOP common data model. We defined two non-mutually exclusive cohorts of patients diagnosed and/or hospitalized with COVID-19; patients were followed from index date to 30 days or death. We report the frequency of demographics, prior medical conditions, and 30-days outcomes (hospitalization, events, and death) by obesity status. Results We included 627 044 (Spain: 122 058, UK: 2336, and US: 502 650) diagnosed and 160 013 (Spain: 18 197, US: 141 816) hospitalized patients with COVID-19. The prevalence of obesity was higher among patients hospitalized (39.9%, 95%CI: 39.8-40.0) than among those diagnosed with COVID-19 (33.1%; 95%CI: 33.0-33.2). In both cohorts, PLWO were more often female. Hospitalized PLWO were younger than patients without obesity. Overall, COVID-19 PLWO were more likely to have prior medical conditions, present with cardiovascular and respiratory events during hospitalization, or require intensive services compared to COVID-19 patients without obesity. Conclusion We show that PLWO differ from patients without obesity in a wide range of medical conditions and present with more severe forms of COVID-19, with higher hospitalization rates and intensive services requirements. These findings can help guiding preventive strategies of COVID-19 infection and complications and generating hypotheses for causal inference studies.
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| 26. |
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| 27. |
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| 28. |
- Bauermeister, S, et al.
(författare)
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The Dementias Platform UK (DPUK) Data Portal
- 2020
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Ingår i: European journal of epidemiology. - : Springer Science and Business Media LLC. - 1573-7284 .- 0393-2990. ; 35:6, s. 601-611
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Tidskriftsartikel (refereegranskat)abstract
- The Dementias Platform UK Data Portal is a data repository facilitating access to data for 3 370 929 individuals in 42 cohorts. The Data Portal is an end-to-end data management solution providing a secure, fully auditable, remote access environment for the analysis of cohort data. All projects utilising the data are by default collaborations with the cohort research teams generating the data. The Data Portal uses UK Secure eResearch Platform infrastructure to provide three core utilities: data discovery, access, and analysis. These are delivered using a 7 layered architecture comprising: data ingestion, data curation, platform interoperability, data discovery, access brokerage, data analysis and knowledge preservation. Automated, streamlined, and standardised procedures reduce the administrative burden for all stakeholders, particularly for requests involving multiple independent datasets, where a single request may be forwarded to multiple data controllers. Researchers are provided with their own secure ‘lab’ using VMware which is accessed using two factor authentication. Over the last 2 years, 160 project proposals involving 579 individual cohort data access requests were received. These were received from 268 applicants spanning 72 institutions (56 academic, 13 commercial, 3 government) in 16 countries with 84 requests involving multiple cohorts. Projects are varied including multi-modal, machine learning, and Mendelian randomisation analyses. Data access is usually free at point of use although a small number of cohorts require a data access fee.
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| 29. |
- Moller, P, et al.
(författare)
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Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: first report from the prospective Lynch syndrome database
- 2017
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 66:3, s. 464-472
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Tidskriftsartikel (refereegranskat)abstract
- Estimates of cancer risk and the effects of surveillance in Lynch syndrome have been subject to bias, partly through reliance on retrospective studies. We sought to establish more robust estimates in patients undergoing prospective cancer surveillance.DesignWe undertook a multicentre study of patients carrying Lynch syndrome-associated mutations affectingMLH1,MSH2,MSH6orPMS2. Standardised information on surveillance, cancers and outcomes were collated in an Oracle relational database and analysed by age, sex and mutated gene.Results1942 mutation carriers without previous cancer had follow-up including colonoscopic surveillance for 13 782 observation years. 314 patients developed cancer, mostly colorectal (n=151), endometrial (n=72) and ovarian (n=19). Cancers were detected from 25 years onwards inMLH1andMSH2mutation carriers, and from about 40 years inMSH6andPMS2carriers. Among first cancer detected in each patient the colorectal cancer cumulative incidences at 70 years by gene were 46%, 35%, 20% and 10% forMLH1, MSH2, MSH6andPMS2mutation carriers, respectively. The equivalent cumulative incidences for endometrial cancer were 34%, 51%, 49% and 24%; and for ovarian cancer 11%, 15%, 0% and 0%. Ten-year crude survival was 87% after any cancer, 91% if the first cancer was colorectal, 98% if endometrial and 89% if ovarian.ConclusionsThe four Lynch syndrome-associated genes had different penetrance and expression. Colorectal cancer occurred frequently despite colonoscopic surveillance but resulted in few deaths. Using our data, a website has been established athttp://LScarisk.orgenabling calculation of cumulative cancer risks as an aid to genetic counselling in Lynch syndrome.
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| 30. |
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| 31. |
- Morales, D. R., et al.
(författare)
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Characteristics and outcomes of COVID-19 patients with and without asthma from the United States, South Korea, and Europe
- 2023
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Ingår i: Journal of Asthma. - : Informa UK Limited. - 0277-0903 .- 1532-4303. ; 60:1, s. 76-86
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Large international comparisons describing the clinical characteristics of patients with COVID-19 are limited. The aim of the study was to perform a large-scale descriptive characterization of COVID-19 patients with asthma. Methods: We included nine databases contributing data from January to June 2020 from the US, South Korea (KR), Spain, UK and the Netherlands. We defined two cohorts of COVID-19 patients ('diagnosed' and 'hospitalized') based on COVID-19 disease codes. We followed patients from COVID-19 index date to 30 days or death. We performed descriptive analysis and reported the frequency of characteristics and outcomes in people with asthma defined by codes and prescriptions. Results: The diagnosed and hospitalized cohorts contained 666,933 and 159,552 COVID-19 patients respectively. Exacerbation in people with asthma was recorded in 1.6-8.6% of patients at presentation. Asthma prevalence ranged from 6.2% (95% CI 5.7-6.8) to 18.5% (95% CI 18.2-18.8) in the diagnosed cohort and 5.2% (95% CI 4.0-6.8) to 20.5% (95% CI 18.6-22.6) in the hospitalized cohort. Asthma patients with COVID-19 had high prevalence of comorbidity including hypertension, heart disease, diabetes and obesity. Mortality ranged from 2.1% (95% CI 1.8-2.4) to 16.9% (95% CI 13.8-20.5) and similar or lower compared to COVID-19 patients without asthma. Acute respiratory distress syndrome occurred in 15-30% of hospitalized COVID-19 asthma patients. Conclusion: The prevalence of asthma among COVID-19 patients varies internationally. Asthma patients with COVID-19 have high comorbidity. The prevalence of asthma exacerbation at presentation was low. Whilst mortality was similar among COVID-19 patients with and without asthma, this could be confounded by differences in clinical characteristics. Further research could help identify high-risk asthma patients. KEY MESSAGES Asthma prevalence in COVID-19 patients varied internationally (5.2-20.5%).The prevalence of asthma exacerbation at presentation with COVID-19 in diagnosed and hospitalized patients was low.Comorbidities were common in COVID-19 patients with asthma. Supplemental data for this article is available online at https://doi.org/10.1080/02770903.2021.2025392 .
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- Moller, P, et al.
(författare)
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Cancer risk and survival in path_MMR carriers by gene and gender up to 75 years of age: a report from the Prospective Lynch Syndrome Database
- 2018
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 67:7, s. 1306-1316
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Tidskriftsartikel (refereegranskat)abstract
- Most patients with path_MMR gene variants (Lynch syndrome (LS)) now survive both their first and subsequent cancers, resulting in a growing number of older patients with LS for whom limited information exists with respect to cancer risk and survival.Objective and designThis observational, international, multicentre study aimed to determine prospectively observed incidences of cancers and survival in path_MMR carriers up to 75 years of age.Results3119 patients were followed for a total of 24 475 years. Cumulative incidences at 75 years (risks) for colorectal cancer were 46%, 43% and 15% in path_MLH1, path_MSH2 and path_MSH6 carriers; for endometrial cancer 43%, 57% and 46%; for ovarian cancer 10%, 17% and 13%; for upper gastrointestinal (gastric, duodenal, bile duct or pancreatic) cancers 21%, 10% and 7%; for urinary tract cancers 8%, 25% and 11%; for prostate cancer 17%, 32% and 18%; and for brain tumours 1%, 5% and 1%, respectively. Ovarian cancer occurred mainly premenopausally. By contrast, upper gastrointestinal, urinary tract and prostate cancers occurred predominantly at older ages. Overall 5-year survival for prostate cancer was 100%, urinary bladder 93%, ureter 85%, duodenum 67%, stomach 61%, bile duct 29%, brain 22% and pancreas 0%. Path_PMS2 carriers had lower risk for cancer.ConclusionCarriers of different path_MMR variants exhibit distinct patterns of cancer risk and survival as they age. Risk estimates for counselling and planning of surveillance and treatment should be tailored to each patient’s age, gender and path_MMR variant. We have updated our open-access website www.lscarisk.org to facilitate this.
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- Sena, AG, et al.
(författare)
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FIRST LINE TREATMENT WITH CONVENTIONAL SYNTHETIC DISEASE MODIFYING ANTIRHEUMATIC DRUGS IN RHEUMATOID ARTHRITIS: A MULTINATIONAL POPULATION-BASED COHORT FROM 14 REAL WORLD HEALTHCARE DATABASES AND 9 COUNTRIES - REALITY VERSUS GUIDELINES
- 2020
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 79, s. 327-327
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Treatment guidelines recommend early initiation of csDMARDs following diagnosis of rheumatoid arthritis (RA), with methotrexate (MTX) as first-line therapy. Scarce evidence exists on adherence to this guidanceObjectives:To characterize first-line csDMARD treatment during the first year following an RA diagnosis.Methods:14 real world databases (3 Primary care, 6 primary/secondary care records, 5 claims) from 9 countries were included, all mapped to the OMOP common data model.Patients were included on the earliest event of: 1st diagnosis of RA or 1st DMARD prescription with an RA diagnosis within 30 days. Patients were >18 years-old, required 1+ year pre-index data, and at least 1-year follow-up. Study period covered 2000-2018. Previous users of DMARDs or non-RA inflammatory arthritis history were excluded. Only MTX, Hydroxychloroquine (HCQ), Sulfasalazine (SSZ) and Leflunomide (LEF) were available in all databases.Results:We identified 323,547 eligible participants. Large variation was observed internationally (Figure 1). MTX as first-line monotherapy ranged from 33.3% to 74.5%, and in combination with HCQ from 2.1% to 6.7%. Three additional csDMARDs were used as first-line: HCQ in 10.1% to 30.2%, SSZ in 0.9% to 28.7%, and LEF in 1.8% to 15.2%.Figure 1.First line csDMARD treatment during 1yr from first observed RA diagnosisConclusion:We report wide heterogeneity of first-line csDMARDs regimens internationally. Despite recommendations for MTX to be first line therapy, data suggest that a large proportion of patients receive alternative csDMARD.Disclosure of Interests: :Anthony G Sena Shareholder of: J&J shares, Grant/research support from: Full-time employment salary from Janssen, Consultant of: Full-time employment salary from Janssen, Employee of: Janssen employee, Paid instructor for: Janssen employee, Speakers bureau: Janssen employee, Denis Granados: None declared, Nigel Hughes Shareholder of: J&J shares, Grant/research support from: Full-time employment salary from Janssen, Consultant of: Janssen employee, Employee of: Janssen employee, Paid instructor for: Janssen employee, Speakers bureau: Janssen employee, WALID FAKHOURI Shareholder of: E Lilly Shares, Employee of: Eli Lilly and Company, Antje Hottgenroth Shareholder of: Eli Lilly shares, Employee of: Lilly Deutschland GmbH, Raivo Kolde: None declared, Sulev Reisberg: None declared, Carmen Olga Torre: None declared, Talita Duarte-Salles: None declared, Yesika Díaz: None declared, Jose Felipe Golib-Dzib Grant/research support from: Full-time employment salary from Janssen, Employee of: Yes, Janssen employee, Paid instructor for: Janssen Employee, Speakers bureau: Janssen Employee, Emily S. Brouwer Shareholder of: J&J shares, Takeda shares, Grant/research support from: Full-time employment salary from Janssen, Consultant of: Janssen employee, Employee of: Janssen employee, Paid instructor for: Janssen Employee, Speakers bureau: Janssen Employee, Edward Burn: None declared, Jennifer Lane: None declared, David Vizcaya Employee of: Bayer, Sara Bruce Wirta Employee of: Janssen-Cilag Sweden AB, Marcel de Wilde: None declared, Katia Verhamme: None declared, Peter Rijnbeek: None declared, Elke Theander Employee of: Janssen-Cilag Sweden AB, Katerina Chatzidionysiou Consultant of: AbbVie, Pfizer, Lilly., Daniel Prieto-Alhambra Grant/research support from: Professor Prieto-Alhambra has received research Grants from AMGEN, UCB Biopharma and Les Laboratoires Servier, Consultant of: DPA’s department has received fees for consultancy services from UCB Biopharma, Speakers bureau: DPA’s department has received fees for speaker and advisory board membership services from Amgen, Patrick Ryan: None declared
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- Patrinos, George P., et al.
(författare)
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Human variome project country nodes: Documenting genetic information within a country
- 2012
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Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794. ; 33:11, s. 1513-1519
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Tidskriftsartikel (refereegranskat)abstract
- The Human Variome Project (http://www.humanvariomeproject.org) is an international effort aiming to systematically collect and share information on all human genetic variation. The two main pillars of this effort are gene/disease-specific databases and a network of Human Variome Project Country Nodes. The latter are nationwide efforts to document the genomic variation reported within a specific population. The development and successful operation of the Human Variome Project Country Nodes are of utmost importance to the success of Human Variome Project's aims and goals because they not only allow the genetic burden of disease to be quantified in different countries, but also provide diagnosticians and researchers access to an up-to-date resource that will assist them in their daily clinical practice and biomedical research, respectively. Here, we report the discussions and recommendations that resulted from the inaugural meeting of the International Confederation of Countries Advisory Council, held on 12th December 2011, during the 2011 Human Variome Project Beijing Meeting. We discuss the steps necessary to maximize the impact of the Country Node effort for developing regional and country-specific clinical genetics resources and summarize a few well-coordinated genetic data collection initiatives that would serve as paradigms for similar projects. Hum Mutat 33:15131519, 2012. (c) 2012 Wiley Periodicals, Inc.
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