Agreement between dual x-ray absorptiometers using pencil beam and fan beam: indicators of bone health and whole-body plus appendicular tissue composition in adult athletes

OBJECTIVE: The current study was aimed to examine intra-individual variation on indicators of bone health in addition to whole-body plus appendicular tissue measurements using two concurrent assessments based on pencil beam and fan beam dual energy X-ray absorptiometry (DXA) systems in adult athletes from several sports. METHOD: Thirty-two male participants (27.6±10.1 years) were measured on anthropometry including multifrequency bioelectric impedance and air-displacement plethysmography. Bone mineral content (BMC), bone area, fat and lean soft tissue were derived using pencil beam (Lunar DPX-MD+) and fan beam (Lunar iDXA) absorptiometry. Bone mineral density (BMD) was obtained for the femoral neck, trochanter and triangle of ward. Finally, the right thigh was defined as a region of interest (ROI). Analyses comprised intra-class correlation (ICC), Effect size (d) from mean differences of repeated measurements, coefficient of variation (CV) RESULTS: ICC were >0.900 for all measurements. Intra-individual differences were large for BMC (d=1,312; CV=2,7%), bone area (d=1,761; CV=2,7%), fat tissue (d=1,612; CV=11%) and all indicators of appendicular lean soft tissue (d=1,237-1687; CV=2,0-4,1%). A very large difference (d=4,014; CV=8.4%) was diagnosed for lean soft tissue of the ROI. CONCLUSION: Although differences among concurrent instruments for BMC and bone area, the effect size of mean differences was negligible for BMD. Fat and lean soft tissue derived from DXA should be interpreted as reference values (not criterion) due to equipment-related variation, more apparently in the ROI values.info:eu-repo/semantics/publishedVersio

Disease-Modifying Therapies and Coronavirus Disease 2019 Severity in Multiple Sclerosis

Objective: This study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (PwMS). Methods: We retrospectively collected data of PwMS with suspected or confirmed COVID-19. All the patients had complete follow-up to death or recovery. Severe COVID-19 was defined by a 3-level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID-19 by multivariate and propensity score (PS)-weighted ordinal logistic models. Sensitivity analyses were run to confirm the results. Results: Of 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID-19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti-CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18-4.74, p = 0.015) with increased risk of severe COVID-19. Recent use (<1 month) of methylprednisolone was also associated with a worse outcome (OR = 5.24, 95% CI = 2.20-12.53, p = 0.001). Results were confirmed by the PS-weighted analysis and by all the sensitivity analyses. Interpretation: This study showed an acceptable level of safety of therapies with a broad array of mechanisms of action. However, some specific elements of risk emerged. These will need to be considered while the COVID-19 pandemic persists

COVID-19 Severity in Multiple Sclerosis: Putting Data Into Context

Background and objectives: It is unclear how multiple sclerosis (MS) affects the severity of COVID-19. The aim of this study is to compare COVID-19-related outcomes collected in an Italian cohort of patients with MS with the outcomes expected in the age- and sex-matched Italian population. Methods: Hospitalization, intensive care unit (ICU) admission, and death after COVID-19 diagnosis of 1,362 patients with MS were compared with the age- and sex-matched Italian population in a retrospective observational case-cohort study with population-based control. The observed vs the expected events were compared in the whole MS cohort and in different subgroups (higher risk: Expanded Disability Status Scale [EDSS] score > 3 or at least 1 comorbidity, lower risk: EDSS score ≤ 3 and no comorbidities) by the χ2 test, and the risk excess was quantified by risk ratios (RRs). Results: The risk of severe events was about twice the risk in the age- and sex-matched Italian population: RR = 2.12 for hospitalization (p < 0.001), RR = 2.19 for ICU admission (p < 0.001), and RR = 2.43 for death (p < 0.001). The excess of risk was confined to the higher-risk group (n = 553). In lower-risk patients (n = 809), the rate of events was close to that of the Italian age- and sex-matched population (RR = 1.12 for hospitalization, RR = 1.52 for ICU admission, and RR = 1.19 for death). In the lower-risk group, an increased hospitalization risk was detected in patients on anti-CD20 (RR = 3.03, p = 0.005), whereas a decrease was detected in patients on interferon (0 observed vs 4 expected events, p = 0.04). Discussion: Overall, the MS cohort had a risk of severe events that is twice the risk than the age- and sex-matched Italian population. This excess of risk is mainly explained by the EDSS score and comorbidities, whereas a residual increase of hospitalization risk was observed in patients on anti-CD20 therapies and a decrease in people on interferon

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

Search for electroweak production of charginos in final states with two tau leptons in pp collisions at root s=8 TeV

Results are presented from a search for the electroweak production of supersymmetric particles in pp collisions in final states with two T leptons. The data sample corresponds to an integrated luminosity between 18.1 fb(-1) and 19.6 fb(-1) depending on the final state of T lepton decays, at root s = 8 TeV, collected by the CMS experiment at the LHC. The observed event yields in the signal regions are consistent with the expected standard model backgrounds. The results are interpreted using simplified models describing the pair production and decays of charginos or T sleptons. For models describing the pair production of the lightest chargino, exclusion regions are obtained in the plane of chargino mass vs. neutralino mass under the following assumptions: the chargino decays into third-generation sleptons, which are taken to be the lightest sleptons, and the sleptons masses lie midway between those of the chargino and the neutralino. Chargino masses below 420 GeV are excluded at a 95% confidence level in the limit of a massless neutralino, and for neutralino masses up to 100 GeV, chargino masses up to 325 GeV are excluded at 95% confidence level. Constraints are also placed on the cross section for pair production of T sleptons as a function of mass, assuming a massless neutralino.Peer reviewe

Preliminary Results of the FASM Study, an On-Going Italian Active Pharmacovigilance Project

Background and aim: Disease-modifying therapies (DMTs) used in multiple sclerosis (MS) have distinct safety profiles. In this paper, we report preliminary results of an on-going pharmacovigilance project (the FASM study). Results: Neurologists working at involved multiple sclerosis centers collected 272 Individual Case Safety Reports (ICSRs). Adverse drug reactions (ADRs) mainly occurred in adult patients and in a higher percentage of women compared to men. No difference was found in ADRs distribution by seriousness. The outcome was reported as favorable in 61% of ICSRs. Out of 272 ICSRs, almost 53% reported dimethyl fumarate, fingolimod and IFN beta 1a as suspected. These medications were commonly associated to the occurrence of ADRs related hematological, gastrointestinal, general, infective or cancer disorders. The median time to event (days) was 177 for dimethyl fumarate, 1058 for fingolimod and 413 for IFN beta 1a. The median time to event for the remaining suspected drugs was 226. Conclusion: We believe that our results, together with those that will be presented at the end of the study, may bring new knowledge concerning the safety profile of DMTs and their proper use. This will provide the opportunity to draw new recommendations both for neurologists and patients

Predictors of Cladribine Effectiveness and Safety in Multiple Sclerosis: A Real-World, Multicenter, 2-Year Follow-Up Study

Introduction Cladribine administration has been approved for the treatment of relapsing-remitting multiple sclerosis (MS) in 2017; thus, data on cladribine in a real-world setting are still emerging. Methods We report on cladribine effectiveness, safety profile, and treatment response predictors in 243 patients with MS followed at eight tertiary MS centers. Study outcomes were: (1) No Evidence of Disease Activity-3 (NEDA-3) status and its components (absence of clinical relapses, MRI activity, and sustained disability worsening); (2) development of grade III/IV lymphopenia. The relationship between baseline features and the selected outcomes was tested via multivariate logistic models. Results Of the 243 subjects included in the study (66.5% female, age 34.2 +/- 10 years, disease duration 6.6 +/- 9.6 years), 64% showed NEDA-3 at median follow-up (22 months). Patients with higher number of previous treatments had lower probability to retain NEDA-3 [odds ratio (OR) 0.64, 95% confidence interval (CI) 0.41-0.98, p = 0.04] and were more prone to experience clinical relapses (OR 1.6, 95% CI 1-2.6, p = 0.04). The presence of active lesions at baseline was associated with follow-up magnetic resonance imaging (MRI) activity (OR 1.92, 95% CI 1.04-3.55, p = 0.04). Patients with higher rate of relapses in the year prior to cladribine start were at higher risk of developing sustained disability worsening (OR 2.95% CI 1-4.2, p = 0.04). Lymphopenia grade III/IV over the follow-up was associated with baseline lymphocyte count (OR 0.998, 95% CI 0.997-0.999, p = 0.01). Conclusion In this large cohort, we confirm previous data about cladribine effectiveness on disease activity and disability worsening and provide information on response predictors that might inform therapeutic choices

Prognostic Markers of Ocrelizumab Effectiveness in Multiple Sclerosis: A Real World Observational Multicenter Study

Pivotal trials showed the effectiveness of the monoclonal antibody ocrelizumab in relapsing and progressive multiple sclerosis (MS). However, data on everyday practice in MS patients and markers of treatment effectiveness are scarce. We aimed to collect real-world data from ocrelizumab-treated MS patients, relapsing-remitting (RR) and progressive MS patients (PMS), including active secondary progressive MS (aSPMS) and primary progressive MS (PPMS) patients, and to explore potential prognostic factors of clinical outcome. Patients were enrolled at MS centres in the Campania region, Italy. We collected clinic-demographic features retrospectively one year before ocrelizumab start (T-1), at ocrelizumab start (T0), and after one year from ocrelizumab start (T1). We explored possible clinical markers of treatment effectiveness in those patients receiving ocrelizumab treatment for at least one year using multilevel-mixed models. We included a total of 383 MS patients (89 RRMS and 294 PMS; 205 females, mean age: 45.8 ± 11.2, disease duration: 12.7 ± 11.6 years). Patients had a mean follow-up of 12.4 ± 8.2 months, and 217 patients completed one-year ocrelizumab treatment. Overall, EDSS increased from T-1 to T0 (coeff. = 0.30, 95% coefficient interval [CI] = 0.19-0.41, p < 0.001) without a further change between T0 and T1 (p = 0.61). RRMS patients did not show an EDSS change between T-1 and T0 nor between T0 and T1. Conversely, PMS patients showed EDSS increase from T-1 to T0 (coeff. = 0.34, 95% CI = 0.22-0.45, p < 0.001) without a further change between T0 and T1 (p = 0.21). PMS patients with a time from conversion shorter than 2 years showed increased EDSS from T-1 to T0 (coeff. = 0.63, 95% CI = 0.18-1.08, p = 0.006) without a further change between T0 and T1 (p = 0.94), whereas PMS patients with a time from conversion longer than 2 years showed increased EDSS from T0 to T1 (coeff. = 0.30, 95% CI = 0.11-0.49, p = 0.002). Naïve patients showed an EDSS decrease between T0 and T1 (coeff. = -0.30, 95% CI = -0.50--0.09, p = 0.004). In conclusion, our study highlighted that early ocrelizumab treatment is effective in modifying the disability accrual in MS patients

Risk of multiple sclerosis relapses when switching from fingolimod to cell-depleting agents: the role of washout duration

Background: Fingolimod (FTY) induces sequestration of lymphocytes in secondary lymphoid organs and the average lymphocyte recovery following discontinuation takes 1\u20132 months. It has been hypothesized that the therapeutic effects of subsequent cell-depleting agents may be compromised if initiated before lymphocyte recovery has occurred. Objective: To assess the risk of relapses following FTY discontinuation and the initiation of a B/T cell-depleting agent in relation to washout duration using data from the Italian MS Register. Methods: The risk of relapses was assessed in relation to different washout durations (< 6, 6\u201311, 12\u201317 and > / = 18 weeks) in patients starting alemtuzumab, rituximab, ocrelizumab or cladribine following FTY discontinuation. Results: We included 329 patients in the analysis (226F, 103 M; mean age 41 \ub1 10 years). During the cell-depleting treatment, the incidence rate ratio for a relapse was significantly greater in patients with a washout period of 12\u201317 and > / = 18 weeks compared to the reference period (< 6 weeks). The risk of a relapse was significantly influenced by the occurrence of relapses during FTY treatment and by washout length, with hazard ratios markedly increasing with the washout duration. Conclusion: The risk of relapses increases with the washout duration when switching from FTY to lymphocyte-depleting agents