DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

États de mal épileptique convulsifs ventilés à la phase initiale : étude rétrospective multicentrique du taux d’états de mal réfractaires et des modalités de gestion de l’anesthésie générale à la phase précoce en réanimation

Convulsive status epilepticus (CSE) frequently requires mechanical ventilation (MV), either for general anesthesia (GA) in case of refractory SE (recommended duration of 24-48h), or for airway protection. Our objective is to evaluate the proportion of refractory generalized CSE (RGCSE) among patients admitted in ICU under MV, to describe early management of GA and prognosis of these patients. This multicenter retrospective study, conducted in fourFrench ICUs between 2014 and 2016, included patients who were intubated before admission in ICU for SE management. Post anoxic SE and acute traumatic brain injuries were excluded. SE characteristics, antiepileptic drugs (AEDs), reason for intubation, GA duration, relapse of SE and complications were studied. Among the 248 files reviewed, 100 were included. Eighty-seven patients had GCSE and 16% of them had RGCSE. The main reason for intubation was coma (58%) and about one third of patients received GA immediately after failure of first line AED, without any second line. Median duration of GA before weaning was 12.25h [5-18.0], without significant difference between RGCSE and non-refractory SE (respectively 12.75h and 12h, p=0.8). Relapse of SE occurred in 7% of cases, and death in 3%. A duration of GA ≤12h before weaning was associated with less complications, without increasing relapse of SE. Morbidity associated with SE may be decreased if the safety of a GA duration ≤12h in RSE is confirmed by prospective data.L’état de mal épileptique (EME) convulsif requiert souvent une ventilation mécanique (VM) : pour anesthésie générale (AG) en cas d’EME réfractaire (durée recommandée de 24-48h) ou pour protection respiratoire. L’objectif est d’évaluer le taux d’EME convulsifs généralisés réfractaires (EME-G-R) parmi les patients admis en réanimation sous VM pour EMEconvulsif, de décrire la gestion de l’AG à la phase précoce et le pronostic de ces patients. Cette étude rétrospective multicentrique, réalisée dans quatre unités de réanimation entre 2014 et 2016, a pour critères d’inclusion : admission en réanimation pour EME convulsif et intubation avant l’entrée. Les EME post-anoxiques et les traumatismes crâniens aigus ont été exclus. Les caractéristiques de l’EME, les traitements antiépileptiques (AE), la cause d’intubation, la durée de l’AG, la récidive d’EME et les complications ont été recueillis. Sur les 248 dossiers éligibles, 100 ont été inclus. Parmi les 87 EME convulsifs généralisés, 16% sont réfractaires. La raison principale d’intubation est le coma (58%) et un tiers des patients sont mis directement sous AG sans 2ème ligne d’AE en cas de persistance des convulsions après la 1ère ligne d’AE. La durée médiane d’AG avant sevrage est de 12.25h [5-18.0], sans différence entre EME-G-R et non réfractaire (respectivement 12.75h et 12h, p=0.8). Le taux de récidive d’EME est de 7%, et de décès de 3%. Une durée d’AG =12h avant sevrage est associée à un taux de complications moindre, sans majorer les récidives.La morbi-mortalité liée aux EME pourrait être diminuée si la sécurité d’une AG =12h est confirmée par des données prospectives dans l’EME réfractaire

Unexpected REM Sleep Excess Associated with a Pontine Lesion in Multiple Sclerosis

International audienceSleep disorders are prevalent in patients with multiple sclerosis. In contrast, a frank increase of REM sleep time is a rare phenomenon, mostly described in the context of REM sleep rebound (after sleep deprivation, abrupt withdrawal of antidepressants or neuroleptics, and during the first night of ventilation for severe sleep apnea), but not in link with specific brain lesions. We incidentally found an isolated, marked increase in REM sleep time (200 min, 40% of total sleep time, normative values: 18.2-20.3%) and in rapid eye movements density during REM sleep in a patient with a secondary progressive multiple sclerosis, associated with an anterior pontine demyelinating lesion on MRI. This result suggests that a network blocking REM sleep in the pons has been damaged

The “Neurospeed” game: a fun tool to learn the neurological semiology

International audienceBackground: Neurological semiology is often considered by medical students as particularly difficult to learn. Finding alternative teaching methods may improve students' motivation and understanding of this field. Methods: We developed the "Neurospeed", a game to learn neurological syndromes. We assessed its efficiency on short-term learning of neurological syndromes in third-year medical students, through Multiple Choice Questions (MCQs) before and after the game session. Students' satisfaction was evaluated by a satisfaction survey. Results: Out of the 199 third-year medical students of the Faculty of Medicine Sorbonne Paris Nord, 180 attended the Neurospeed in December 2020, and 148 answered 20 Multiple Choice Questions before and after the game, with significant improvement of their score (p < 0.001). Most of the participants agreed that the game was playful, stimulating, and helpful to learn neurological semiology. Conclusions: Overall, our results show that the Neurospeed game is an interesting tool as a complement to traditional lectures. Further studies are necessary to compare the efficacy of different types of serious games on short-term and long-term learning of neurological semiology

Not all patients with convulsive status epilepticus intubated in pre-hospital settings meet the criteria for refractory status epilepticus

International audienceIntroduction: Mechanically ventilated patients admitted to the intensive care unit (ICU) for generalized convulsive status epilepticus (GCSE) are a heterogeneous population. Our objective was to evaluate the number of patients who fulfilled the diagnostic criteria for refractory GCSE and describe their initial management and prognosis.Methods: This multicenter retrospective study was conducted in four French ICUs in Pitié-Salpêtrière University Hospital in Paris and in the Hospital of Jossigny. Mechanically ventilated patients admitted to the ICU for GCSE between, January 1, 2014, and, December 31, 2016, were included. Patients with anoxia and traumatic brain injury were excluded. Their pre-hospital and ICU medical records were reviewed. The collected data included pre-hospital clinical status, pre-hospital antiepileptic treatment, reason for mechanical ventilation, duration of general anesthesia, and prognosis in the ICU. A retrospective initial diagnosis based on the findings of the analysis of the clinical records was attributed to each patient.Results: Among the 98 patients included, 88.8% (n = 87/98) fulfilled the diagnostic criteria for GCSE; of these cases, 16.1% (n = 14/87) were refractory. Eleven percent of the patients did not fulfill the criteria for GCSE at the time of initial management (retrospective diagnosis of single convulsive seizure, repetitive convulsive seizures, or psychogenic non-epileptic seizures). Most patients were intubated for coma (58.9%, n = 56/95, missing data: n = 3). In the ICU, the median [Q1-Q3] duration of general anesthesia before weaning was 12.3 h (5.0-18.0 h); 7% of the patients had a relapse of status epilepticus, and 2% died in the ICU.Conclusion: Among the cases of confirmed GCSE in the mechanically ventilated patients admitted to the ICU, 16.1% were refractory, with an overall good prognosis. A significant proportion of patients did not fulfill the diagnostic criteria for refractory GCSE

Outcomes of coronavirus disease 2019 in patients with neuromyelitis optica and associated disorders

International audienceBackground: Outcomes of coronavirus disease 2019 (COVID-19) in patients with neuromyelitis optica spectrum disorders (NMOSD) or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), often treated with immunosuppressive therapies, are still unknown.Methods: We conducted a multicenter, retrospective, observational cohort study among all French expert centers for neuromyelitis optica and related disorders. Patients with NMOSD or MOGAD included in the study received a confirmed or highly suspected diagnosis of COVID-19 between 1 March 2020 and 30 June 2020. Main outcome was COVID-19 severity score assessed on a seven-point ordinal scale ranging from 1 (not hospitalized with no limitations on activities) to 7 (death).Results: Fifteen cases (mean [SD] age: 39.3 [14.3] years, 11 female) were included. Five patients (33.3%) were hospitalized, all receiving rituximab. A 24-year-old patient with positive aquaporine-4 antibody, with obesity as comorbidity, needed mechanical ventilation. Outpatients were receiving anti-CD20 (5), mycophenolate mofetil (3) or azathioprine (3). They were younger (mean [SD] age: 37.0 [13.4] years), with a longer disease duration (mean [SD]: 8.3 [6.3] years) and had a lower expanded disability severity score (EDSS) score (median [range] EDSS: 2.5 [0-4]) relative to patients requiring hospitalization (mean [SD] age: 44.0 [16.4] years, mean [SD] disease duration: 5.8 [5.5] years, median [range] EDSS: 4 [0-6.5]).Conclusions: COVID-19 outcome was overall favorable in this cohort. Larger international studies are needed to identify risk factors of severe COVID-19; however, we recommend personal protective measures to reduce risk of SARS-CoV-2 infection in this immunocompromised population

Cognitive and psychiatric symptom trajectories 2–3 years after hospital admission for COVID-19: a longitudinal, prospective cohort study in the UK

Background: COVID-19 is known to be associated with increased risks of cognitive and psychiatric outcomes after the acute phase of disease. We aimed to assess whether these symptoms can emerge or persist more than 1 year after hospitalisation for COVID-19, to identify which early aspects of COVID-19 illness predict longer-term symptoms, and to establish how these symptoms relate to occupational functioning. Methods: The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a prospective, longitudinal cohort study of adults (aged ≥18 years) who were hospitalised with a clinical diagnosis of COVID-19 at participating National Health Service hospitals across the UK. In the C-Fog study, a subset of PHOSP-COVID participants who consented to be recontacted for other research were invited to complete a computerised cognitive assessment and clinical scales between 2 years and 3 years after hospital admission. Participants completed eight cognitive tasks, covering eight cognitive domains, from the Cognitron battery, in addition to the 9-item Patient Health Questionnaire for depression, the Generalised Anxiety Disorder 7-item scale, the Functional Assessment of Chronic Illness Therapy Fatigue Scale, and the 20-item Cognitive Change Index (CCI-20) questionnaire to assess subjective cognitive decline. We evaluated how the absolute risks of symptoms evolved between follow-ups at 6 months, 12 months, and 2–3 years, and whether symptoms at 2–3 years were predicted by earlier aspects of COVID-19 illness. Participants completed an occupation change questionnaire to establish whether their occupation or working status had changed and, if so, why. We assessed which symptoms at 2–3 years were associated with occupation change. People with lived experience were involved in the study. Findings: 2469 PHOSP-COVID participants were invited to participate in the C-Fog study, and 475 participants (191 [40·2%] females and 284 [59·8%] males; mean age 58·26 [SD 11·13] years) who were discharged from one of 83 hospitals provided data at the 2–3-year follow-up. Participants had worse cognitive scores than would be expected on the basis of their sociodemographic characteristics across all cognitive domains tested (average score 0·71 SD below the mean [IQR 0·16–1·04]; p<0·0001). Most participants reported at least mild depression (263 [74·5%] of 353), anxiety (189 [53·5%] of 353), fatigue (220 [62·3%] of 353), or subjective cognitive decline (184 [52·1%] of 353), and more than a fifth reported severe depression (79 [22·4%] of 353), fatigue (87 [24·6%] of 353), or subjective cognitive decline (88 [24·9%] of 353). Depression, anxiety, and fatigue were worse at 2–3 years than at 6 months or 12 months, with evidence of both worsening of existing symptoms and emergence of new symptoms. Symptoms at 2–3 years were not predicted by the severity of acute COVID-19 illness, but were strongly predicted by the degree of recovery at 6 months (explaining 35·0–48·8% of the variance in anxiety, depression, fatigue, and subjective cognitive decline); by a biocognitive profile linking acutely raised D-dimer relative to C-reactive protein with subjective cognitive deficits at 6 months (explaining 7·0–17·2% of the variance in anxiety, depression, fatigue, and subjective cognitive decline); and by anxiety, depression, fatigue, and subjective cognitive deficit at 6 months. Objective cognitive deficits at 2–3 years were not predicted by any of the factors tested, except for cognitive deficits at 6 months, explaining 10·6% of their variance. 95 of 353 participants (26·9% [95% CI 22·6–31·8]) reported occupational change, with poor health being the most common reason for this change. Occupation change was strongly and specifically associated with objective cognitive deficits (odds ratio [OR] 1·51 [95% CI 1·04–2·22] for every SD decrease in overall cognitive score) and subjective cognitive decline (OR 1·54 [1·21–1·98] for every point increase in CCI-20). Interpretation: Psychiatric and cognitive symptoms appear to increase over the first 2–3 years post-hospitalisation due to both worsening of symptoms already present at 6 months and emergence of new symptoms. New symptoms occur mostly in people with other symptoms already present at 6 months. Early identification and management of symptoms might therefore be an effective strategy to prevent later onset of a complex syndrome. Occupation change is common and associated mainly with objective and subjective cognitive deficits. Interventions to promote cognitive recovery or to prevent cognitive decline are therefore needed to limit the functional and economic impacts of COVID-19. Funding: National Institute for Health and Care Research Oxford Health Biomedical Research Centre, Wolfson Foundation, MQ Mental Health Research, MRC-UK Research and Innovation, and National Institute for Health and Care Research.</p

Prospective observational cohort study on grading the severity of postoperative complications in global surgery research

Background The Clavien–Dindo classification is perhaps the most widely used approach for reporting postoperative complications in clinical trials. This system classifies complication severity by the treatment provided. However, it is unclear whether the Clavien–Dindo system can be used internationally in studies across differing healthcare systems in high- (HICs) and low- and middle-income countries (LMICs). Methods This was a secondary analysis of the International Surgical Outcomes Study (ISOS), a prospective observational cohort study of elective surgery in adults. Data collection occurred over a 7-day period. Severity of complications was graded using Clavien–Dindo and the simpler ISOS grading (mild, moderate or severe, based on guided investigator judgement). Severity grading was compared using the intraclass correlation coefficient (ICC). Data are presented as frequencies and ICC values (with 95 per cent c.i.). The analysis was stratified by income status of the country, comparing HICs with LMICs. Results A total of 44 814 patients were recruited from 474 hospitals in 27 countries (19 HICs and 8 LMICs). Some 7508 patients (16·8 per cent) experienced at least one postoperative complication, equivalent to 11 664 complications in total. Using the ISOS classification, 5504 of 11 664 complications (47·2 per cent) were graded as mild, 4244 (36·4 per cent) as moderate and 1916 (16·4 per cent) as severe. Using Clavien–Dindo, 6781 of 11 664 complications (58·1 per cent) were graded as I or II, 1740 (14·9 per cent) as III, 2408 (20·6 per cent) as IV and 735 (6·3 per cent) as V. Agreement between classification systems was poor overall (ICC 0·41, 95 per cent c.i. 0·20 to 0·55), and in LMICs (ICC 0·23, 0·05 to 0·38) and HICs (ICC 0·46, 0·25 to 0·59). Conclusion Caution is recommended when using a treatment approach to grade complications in global surgery studies, as this may introduce bias unintentionally

The surgical safety checklist and patient outcomes after surgery: a prospective observational cohort study, systematic review and meta-analysis

© 2017 British Journal of Anaesthesia Background: The surgical safety checklist is widely used to improve the quality of perioperative care. However, clinicians continue to debate the clinical effectiveness of this tool. Methods: Prospective analysis of data from the International Surgical Outcomes Study (ISOS), an international observational study of elective in-patient surgery, accompanied by a systematic review and meta-analysis of published literature. The exposure was surgical safety checklist use. The primary outcome was in-hospital mortality and the secondary outcome was postoperative complications. In the ISOS cohort, a multivariable multi-level generalized linear model was used to test associations. To further contextualise these findings, we included the results from the ISOS cohort in a meta-analysis. Results are reported as odds ratios (OR) with 95% confidence intervals. Results: We included 44 814 patients from 497 hospitals in 27 countries in the ISOS analysis. There were 40 245 (89.8%) patients exposed to the checklist, whilst 7508 (16.8%) sustained ≥1 postoperative complications and 207 (0.5%) died before hospital discharge. Checklist exposure was associated with reduced mortality [odds ratio (OR) 0.49 (0.32–0.77); P\u3c0.01], but no difference in complication rates [OR 1.02 (0.88–1.19); P=0.75]. In a systematic review, we screened 3732 records and identified 11 eligible studies of 453 292 patients including the ISOS cohort. Checklist exposure was associated with both reduced postoperative mortality [OR 0.75 (0.62–0.92); P\u3c0.01; I2=87%] and reduced complication rates [OR 0.73 (0.61–0.88); P\u3c0.01; I2=89%). Conclusions: Patients exposed to a surgical safety checklist experience better postoperative outcomes, but this could simply reflect wider quality of care in hospitals where checklist use is routine