Major discrepancies between what clinical trial registries record and paediatric randomised controlled trials publish

Background: Whether information from clinical trial registries (CTRs) and published randomised controlled trial (RCTs) differs remains unknown. Knowing more about discrepancies should alert those who rely on RCTs for medical decision-making to possible dissemination or reporting bias. To provide help in critically appraising research relevant for clinical practice we sought possible discrepancies between what CTRs record and paediatric RCTs actually publish. For this purpose, after identifying six reporting domains including funding, design, and outcomes, we collected data from 20 consecutive RCTs published in a widely read peer-reviewed paediatric journal and cross-checked reported features with those in the corresponding CTRs. Methods: We collected data for 20 unselected, consecutive paediatric RCTs published in a widely read peer-reviewed journal from July to November 2013. To assess discrepancies, two reviewers identified and scored six reporting domains: funding and conflict of interests; sample size, inclusion and exclusion criteria or crossover; primary and secondary outcomes, early study completion, and main outcome reporting. After applying the Critical Appraisal Skills Programme (CASP) checklist, five reviewer pairs cross-checked CTRs and matching RCTs, then mapped and coded the reporting domains and scored combined discrepancy as low, medium and high. Results: The 20 RCTs were registered in five different CTRs. Even though the 20 RCTs fulfilled the CASP general criteria for assessing internal validity, 19 clinical trials had medium or high combined discrepancy scores for what the 20 RCTs reported and the matched five CTRs stated. All 20 RCTs selectively reported or failed to report main outcomes, 9 had discrepancies in declaring sponsorship, 8 discrepancies in the sample size, 9 failed to respect inclusion or exclusion criteria, 11 downgraded or modified primary outcome or upgraded secondary outcomes, and 13 completed early without justification. The CTRs for seven trials failed to index automatically the URL address or the RCT reference, and for 12 recorded RCT details, but the authors failed to report the results. Conclusions: Major discrepancies between what CTRs record and paediatric RCTs publish raise concern about what clinical trials conclude. Our findings should make clinicians, who rely on RCT results for medical decision-making, aware of dissemination or reporting bias. Trialists need to bring CTR data and reported protocols into line with published data

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

La Scienza e l'immaginario

L’attività di divulgazione della cultura scientifica ha un ruolo fondamentale sulla società, sia in termini di applicazioni innovative che di pianificazione dell’ambiente. I ricercatori dell’IAS-CNR di Capo Granitola operano da anni nell’ambito della diffusione della cultura scientifica, attraverso processi complessi e percorsi di divulgazione in partnership con istituti scolastici del territorio, realizzando attività seminariali, convegni direttamente nelle scuole, nonché visite didattiche guidate degli alunni nei laboratori dell’Istituto ed esperimenti interdisciplinari sull’ambiente marino. Tali processi divulgativi si sono sviluppati creando numerosi percorsi, in maniera per certi aspetti analoga a quella per cui dalla mescolanza dei tre colori fondamentali si è in grado di ottenere un numero pressoché illimitato di tinte diverse. Lo scopo di questa “mescolanza” è stato quello di ottenere un ventaglio di competenze e strumentazioni che consentissero di indagare i differenti aspetti dell’ecosistema marino da diversi punti di vista ed in maniera sinergica, tale da restituire un quadro il più ricco possibile di “tinte” e particolari. (Scienza e arte di Salvatore Mazzola) La Scienza e l'immaginario di Angela Cuttitta. Il progetto “La Scienza e l’Immaginario” nasce dalla collaborazione tra l’IAS - CNR di Capo Granitola e l’Accademia di Belle Arti di Palermo, che attraverso un approccio multidisciplinare ha voluto sperimentare l’unione tra il mondo scientifico e quello artistico, mettendo i giovani artisti, attraverso proiezioni e seminari scientifici, nelle condizioni di scoprire il mondo dell’ambiente marino e degli ecosistemi in esso presenti. Il progetto è nato dalla consapevolezza di come sia necessario operare sul piano della diffusione e divulgazione della cultura scientifica nei più vasti contesti sociali, a partire dall’ambito scolastico. Le azioni divulgative mirano, infatti, a diffondere la conoscenza dei processi geologici, chimico-fisici, climatici e biologici in modo pervasivo, non limitato a singole categorie/settori. La funzione strategica di tali azioni è quella di stimolare idee ed iniziative nonché di sviluppare una maggiore sensibilità nei confronti dei fenomeni che ci circondano, quale presupposto essenziale per una corretta programmazione politico-gestionale. Lo spirito che ha mosso tutte gli attori del progetto è stato quello di sensibilizzare gli studenti nei confronti della tutela delle risorse marine proprie del loro territorio e di sviluppare e promuovere la cultura come volano dello sviluppo sostenibile, della pace e dell’integrazione sociale, in armonia con quanto indicato dal Consiglio Europeo di Lisbona 2000. Grazie al lavoro di docenti e di ricercatori, l’arte come forma espressiva si è rivelata uno strumento valido e innovativo di divulgazione della cultura scientifica e ha portato alla creazione di suggestioni sui ragazzi che hanno percepito e realizzato forme e armonie espresse in questa mostra. L’impegno per questa manifestazione rappresenta, quindi, un appuntamento importante con le forze vive siciliane nel campo delle scienze del mare segnatamente ad esperti di biologia, chimica, fisica ed al mondo fantastico dell’arte, al fine di esprimere con le varie tecniche pittoriche un momento di riflessione culturale

Neutralizing antibodies to Omicron after the fourth SARS-CoV-2 mRNA vaccine dose in immunocompromised patients highlight the need of additional boosters

IntroductionImmunocompromised patients have been shown to have an impaired immune response to COVID-19 vaccines.MethodsHere we compared the B-cell, T-cell and neutralizing antibody response to WT and Omicron BA.2 SARS-CoV-2 virus after the fourth dose of mRNA COVID-19 vaccines in patients with hematological malignancies (HM, n=71), solid tumors (ST, n=39) and immune-rheumatological (IR, n=25) diseases. The humoral and T-cell responses to SARS-CoV-2 vaccination were analyzed by quantifying the anti-RBD antibodies, their neutralization activity and the IFN-γ released after spike specific stimulation.ResultsWe show that the T-cell response is similarly boosted by the fourth dose across the different subgroups, while the antibody response is improved only in patients not receiving B-cell targeted therapies, independent on the pathology. However, 9% of patients with anti-RBD antibodies did not have neutralizing antibodies to either virus variants, while an additional 5.7% did not have neutralizing antibodies to Omicron BA.2, making these patients particularly vulnerable to SARS-CoV-2 infection. The increment of neutralizing antibodies was very similar towards Omicron BA.2 and WT virus after the third or fourth dose of vaccine, suggesting that there is no preferential skewing towards either virus variant with the booster dose. The only limited step is the amount of antibodies that are elicited after vaccination, thus increasing the probability of developing neutralizing antibodies to both variants of virus.DiscussionThese data support the recommendation of additional booster doses in frail patients to enhance the development of a B-cell response directed against Omicron and/or to enhance the T-cell response in patients treated with anti-CD20

valutazione dello stress termico in ambienti di lavoro severo freddi: riprogettazione del calcolatore dell’indice ireq in funzione di età e genere.

Il microclima, che definisce il complesso di parametri ambientali e personali che influenzano lo scambio termico tra uomo e ambiente, rappresenta un elemento cruciale all’interno degli ambienti di lavoro. Nonostante il D.lgs. 81/2008 riconosca il microclima come agente fisico, la normativa vigente risulta oggi estremamente generica e poco accurata nel descrivere le strategie di gestione di tale rischio. Nel contesto di questo studio è stata condotta un’analisi del microclima negli ambienti severo freddi, normati dalla UNI EN ISO 11079. Gli obiettivi di questo studio si sono focalizzati sul miglioramento del processo di valutazione del rischio mediante l’innovazione nella metodologia di calcolo del descrittore IREQ. La ricerca ha avuto origine da una fase approfondita di revisione letteraria che ha evidenziato come la versione attuale del calcolatore non tenga in considerazione i parametri soggettivi, tra cui l’età ed il genere degli operatori. Per affrontare questi limiti, è stata proposta una riprogettazione completa, focalizzando le modifiche sull'implementazione dei parametri soggettivi nei codici di calcolo e sul miglioramento dell'esperienza utente. Tali modifiche hanno richiesto l’utilizzo di un’editor di codice sorgente, nello specifico è stato utilizzato Visual Studio Code. Sono state create ulteriori sezioni di codice per l’implementazione della nuova metodologia di calcolo che richiede in ingresso dati come la frequenza cardiaca. Infine è stato condotto uno studio sul campo per valutare le differenze soggettive tra i lavoratori, evidenziando l'impatto significativo di parametri come l'età e il genere nella determinazione degli output. Questa ricerca nata con l’obiettivo di fornire un contributo aggiuntivo nella comprensione del microclima negli ambienti severo freddi, offre un approccio più accurato e adattabile per valutare il rischio di esposizione al freddo in contesti lavorativi specifici

Mannose-Binding Lectin: Biologic Characteristics and Role in the Susceptibility to Infections and Ischemia-Reperfusion Related Injury in Critically Ill Neonates

The mannose-binding lectin (MBL) is a member of the collectin family, belonging to the innate immunity system. Genetic, biologic, and clinical properties of MBL have been widely investigated throughout the last decades, although some interesting aspects of its potential clinical relevance are still poorly understood. Low circulating concentrations of MBL have been associated with increased risk of infection and poor neurologic outcome in neonates. On the other hand, an excessive and uncontrolled inflammatory response by the neonatal intestine after the exposure to luminal bacteria, leading to an increased production of MBL, may be involved in the onset of necrotizing enterocolitis. The purpose of the present review is to summarize the current knowledge about genetic and biologic characteristics of MBL and its role in the susceptibility to infections and to ischemia-reperfusion related tissue injuries to better explore its clinical relevance during the perinatal period and the possible future therapeutic applications