Clinical Profiles in Multiple Sclerosis: Cognitive Reserve and Motor Impairment along Disease Duration

(i) Background: Cognitive impairment in people with multiple sclerosis (MS) has been studied in relation to certain clinical variables (e.g., motor disability and disease duration) and lifestyle factors such as cognitive reserve (CR). However, only very few studies have considered the interaction of clinical variables and cognitive reserve in preserving the integrity of the neuropsychological profile. In this paper, we hypothesised that a higher level of CR might predict good cognitive efficiency by modulating the clinical outcome of the disease. (ii) Methods: A sample of 100 participants with MS (age range 30–74), was recruited and assessed remotely with a questionnaire to measure CR and a cognitive screening test. Data were analysed through generalized additive models. (iii) Results: We found that the model analysing the interaction between CR and disease duration, and between CR and motor disability, was able to explain a significant percentage of cognitive performance. In particular, higher levels of CR predicted a better cognitive performance despite a long disease duration, unless the motor disability was severe. (iv) Conclusion: This study highlights the crucial role of CR in modulating cognitive efficiency in people with MS

Tele‐Global Examination of Mental State (Tele‐GEMS): an open tool for the remote neuropsychological screening

Tele-neuropsychology, i.e., the application of remote audio-visual technologies to neuropsychological evaluation or rehabilitation, has become increasingly popular and widespread during and after the COVID-19 pandemic. New tools with updated normative data and appropriate methodological developments are necessary. We present Tele-GEMS, a telephone-based cognitive screening developed on N = 601 Italian participants. It yields a global score tapping on orientation, memory, spatial representation, language, and pragmatic abilities. Its administration lasts about 10 min. Clinical cut-offs are provided, accounting for demographic variables (age, education, and sex) and also for a comprehensive index taking into account cognitively stimulating life experiences that can build up a cognitive reserve. Tele-GEMS shows good internal consistency and a good inter-rater agreement. The test includes the thresholds for estimating a signifcant change after repeated meas- urements. Tele-GEMS has a good construct validity as assessed with MoCA and a suitable criterion validity assessed with its in-person version (GEMS). All the materials and the instructions, including scripts and an online Application for the automatic calculation of cut-offs, are accessible on OSF at https://osf.io/t3bma/ under a Creative Commons license

Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial

BackgroundTocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients.MethodsA multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival.ResultsIn the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6-24.0, P=0.52) and 22.4% (97.5% CI: 17.2-28.3, P<0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline.ConclusionsTocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline.Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092)