Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Tests of information processing speed: What do people with multiple sclerosis think about them?

Reduction in information processing speed (IPS) is a key deficit in multiple sclerosis (MS). The Paced Auditory Serial Addition Test (PASAT), Symbol Digit Modalities Test (SDMT), and Computerized Test of Information Processing (CTIP) are used to measure IPS. Both the PASAT and SDMT are sensitive to deficits in IPS. The CTIP, a newer task, also shows promise. The PASAT has several limitations, and it is often perceived negatively by patients. Yet little supporting quantitative evidence of such perceptions has been presented. Therefore, in this study, subjective ratings of likeability, difficulty, and appropriateness of the PASAT, CTIP, and SDMT were obtained. Ratings were compared between MS patients and healthy controls. It was hypothesized that ratings of the PASAT would differ significantly from those of the SDMT and CTIP. The relationship between subjective ratings and objective performance was evaluated. Sixty-nine MS patients and 68 matched controls rated the three tests in terms of likeability, difficulty, and appropriateness for capturing cognitive deficits often associated with MS using a Likert scale. Both groups rated the PASAT as most difficult and least likeable. The MS group rated the PASAT and SDMT as more appropriate for measuring MS-related deficits than the CTIP. Subjects who performed better on the PASAT were more likely to rate it as easier. Ratings of the SDMT and CTIP did not vary consistently with performance. The findings lend quantitative support to the common belief that the PASAT is perceived as unpleasant. Other tests are available that are similarly sensitive to deficits in IPS and more palatable to the patient

Tests of information processing speed: What do people with multiple sclerosis think about them?

Reduction in information processing speed (IPS) is a key deficit in multiple sclerosis (MS). The Paced Auditory Serial Addition Test (PASAT), Symbol Digit Modalities Test (SDMT), and Computerized Test of Information Processing (CTIP) are used to measure IPS. Both the PASAT and SDMT are sensitive to deficits in IPS. The CTIP, a newer task, also shows promise. The PASAT has several limitations, and it is often perceived negatively by patients. Yet little supporting quantitative evidence of such perceptions has been presented. Therefore, in this study, subjective ratings of likeability, difficulty, and appropriateness of the PASAT, CTIP, and SDMT were obtained. Ratings were compared between MS patients and healthy controls. It was hypothesized that ratings of the PASAT would differ significantly from those of the SDMT and CTIP. The relationship between subjective ratings and objective performance was evaluated. Sixty-nine MS patients and 68 matched controls rated the three tests in terms of likeability, difficulty, and appropriateness for capturing cognitive deficits often associated with MS using a Likert scale. Both groups rated the PASAT as most difficult and least likeable. The MS group rated the PASAT and SDMT as more appropriate for measuring MS-related deficits than the CTIP. Subjects who performed better on the PASAT were more likely to rate it as easier. Ratings of the SDMT and CTIP did not vary consistently with performance. The findings lend quantitative support to the common belief that the PASAT is perceived as unpleasant. Other tests are available that are similarly sensitive to deficits in IPS and more palatable to the patient

Cognition in early relapsing-remitting multiple sclerosis: Consequences may be relative to working memory

Abstract The Relative Consequence Model proposes multiple sclerosis (MS) patients have a fundamental deficit in processing speed that compromises other cognitive functions. The present study examined the mediating role of processing speed, as well as working memory, in the MS-related effects on other cognitive functions for early relapsing-remitting patients. Seventy relapsing-remitting MS patients with disease duration not greater than 10 years and 72 controls completed tasks assessing processing speed, working memory, learning, and executive functioning. The possible mediating roles of speed and working memory in the MS-related effects on other cognitive functions were evaluated using structural equation modeling. Processing speed was not significantly related to group membership and could not have a mediating role. Working memory was related to group membership and functioned as a mediating/intervening factor. The results do not support the Relative Consequence Model in this sample and they challenge the notion that working memory impairment only emerges at later disease stages. The results do support a mediating/intervening role of working memory. These results were obtained for early relapsing-remitting MS patients and should not be generalized to the broader MS population. Instead, future research should examine the relations that exist at other disease stages. (JINS, 2013, 19, 1-12) Copyrigh

Reliability of regression-based normative data for the oral symbol digit modalities test: An evaluation of demographic influences, construct validity, and impairment classification rates in multiple sclerosis samples

The oral Symbol Digit Modalities Test (SDMT) has been recommended to assess cognition for multiple sclerosis (MS) patients. However, the lack of adequate normative data has limited its clinical utility. Recently published regression-based norms may resolve this limitation but, because these norms were derived from a relatively small sample, their stability is unclear. We aimed to evaluate the stability of regression-based SDMT norms by comparing existing norms to a cross-validation dataset. First, regression-based normative data were created from a similarly-sized, independent, control sample (n = 94). Next the original and cross-validation norms were compared for equivalency, management of demographic influences, construct validity, and impairment classification rates in a mildly affected MS sample (n = 70). Lastly, similar comparisons were made for a large, representative MS clinic sample (n = 354). We found construct validity and management of demographic influences were equivalent for the two sets of regression-based norms but lower T-scores were obtained using the original dataset, resulting in discrepancies in impairment classification. In conclusion, regression-based norms for the oral SDMT attenuate demographic influences and possess adequate construct validity. However, norms generated using small samples may yield unreliable classification of cognitive impairment. Larger, representative databases will be necessary to improve the clinical utility of regression-based norms

Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS): Canadian contribution to the international validation project

Background Given the high prevalence of cognitive dysfunction in people with multiple sclerosis (PWMS) and the lack of availability of specialized neuropsychological services in most MS Clinics, there is a need for a brief cognitive monitoring tool that can be easily administered by MS clinic staff. Objective We aimed to establish the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) as a feasible cognitive monitoring tool and provide Canadian data toward the international validation effort. Secondary considerations were to determine if BICAMS correlates with self-reported cognition and predicted vocational status. Methods 57 PWMS were matched to 51 healthy controls (age, sex, education). Participants completed the BICAMS battery which includes the Symbol Digit Modalities Test, and the learning trials from the California Verbal Learning Test-II and the Brief Visuospatial Memory Test-Revised. Depression, self-reported cognition, and fatigue were assessed. Participants were re-tested 15.6 (SD 2.0) days later. Results With impairment defined as "one or more abnormal tests," 57.9% of MS sample was cognitively impaired. Participants were more likely to be impaired on the BVMT-R (43.9%). On the SDMT and CVLT-II, 28.1% and 26.3% of MS participants were impaired. Sensitivity and specificity were highest for the SDMT. The BICAMS was reliable over time (r value range from 0.69 for BVMT-R to 0.87 for SDMT) with the SDMT being most robust. There was no relationship between BICAMS and subjective cognition. The BVMT-R reliably predicted employment. Conclusions The BICAMS detected cognitive impairment to a comparable degree to more comprehensive neuropsychological batteries and is a valid measure of cognition in MS. Reliability of components varies, suggesting care be taken when interpreting serial testing results. The BICAMS is a feasible cognitive assessment tool in Canadians and yields comparable results to other cultures

Author Correction: Global status and conservation potential of reef sharks

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.</p

Search for intermediate-mass black hole binaries in the third observing run of Advanced LIGO and Advanced Virgo

International audienceIntermediate-mass black holes (IMBHs) span the approximate mass range 100−105 M⊙, between black holes (BHs) that formed by stellar collapse and the supermassive BHs at the centers of galaxies. Mergers of IMBH binaries are the most energetic gravitational-wave sources accessible by the terrestrial detector network. Searches of the first two observing runs of Advanced LIGO and Advanced Virgo did not yield any significant IMBH binary signals. In the third observing run (O3), the increased network sensitivity enabled the detection of GW190521, a signal consistent with a binary merger of mass ∼150 M⊙ providing direct evidence of IMBH formation. Here, we report on a dedicated search of O3 data for further IMBH binary mergers, combining both modeled (matched filter) and model-independent search methods. We find some marginal candidates, but none are sufficiently significant to indicate detection of further IMBH mergers. We quantify the sensitivity of the individual search methods and of the combined search using a suite of IMBH binary signals obtained via numerical relativity, including the effects of spins misaligned with the binary orbital axis, and present the resulting upper limits on astrophysical merger rates. Our most stringent limit is for equal mass and aligned spin BH binary of total mass 200 M⊙ and effective aligned spin 0.8 at 0.056 Gpc−3 yr−1 (90% confidence), a factor of 3.5 more constraining than previous LIGO-Virgo limits. We also update the estimated rate of mergers similar to GW190521 to 0.08 Gpc−3 yr−1.Key words: gravitational waves / stars: black holes / black hole physicsCorresponding author: W. Del Pozzo, e-mail: [email protected]† Deceased, August 2020