Neurofilament Light Chain in Adult and Pediatric Multiple Sclerosis:A Promising Biomarker to Better Characterize Disease Activity and Personalize MS Treatment

Many biological markers have been explored in multiple sclerosis (MS) to better quantify disease burden and better evaluate response to treatments, beyond clinical and MRI data. Among these, neurofilament light chain (Nf-L), although non-specific for this disease and found to be increased in other neurological conditions, has been shown to be the most promising biomarker for assessing axonal damage in MS, with a definite role in predicting the development of MS in patients at the first neurological episode suggestive of MS, and also in a preclinical phase. There is strong evidence that Nf-L levels are increased more in relapsing versus stable MS patients, and that they predict future disease evolution (relapses, progression, MRI measures of activity/progression) in MS patients, providing information on response to therapy, helping to anticipate clinical decisions in patients with an apparently stable evolution, and identifying patient non-responders to disease-modifying treatments. Moreover, Nf-L can contribute to the better understanding of the mechanisms of demyelination and axonal damage in adult and pediatric MS. A fundamental requirement for its clinical use is the accurate standardization of normal values, corrected for confounding factors, in particular age, sex, body mass index, and presence of comorbidities. In this review, a guide is provided to update clinicians on the use of Nf-L in clinical activity.</p

Business Model Adaptation: Evidence of Lean Experimentation in Digital Startups

Digital startups frequently adapt their business model, but in doing so they face resource scarcity and need to “make-do” in validating and implementing their design changes at a practical level. We thus argue that digital startups employ a Lean Experimental approach when adapting their BM to contextual conditions. By means of an exploratory multiple-case study on Digital startups, this research investigates the factors driving the deployment of an experimental approach and proposing some factors that may drive differences in its application. Results suggest that most startups dealing with BM adaptation engage in experimentation practices that can be identified with the Lean Startup Approaches (LSAs), although with different extents of application. In this sense, startups move from scarce resource availability in resembling selected elements of the framework, whereas those with higher resource availability seem to be more prone to adopting LSAs in a structured and customized way at the organizational level

Pharmacokinetics and pharmacodynamics of natalizumab in pediatric patients with RRMS

This phase I study investigated pharmacokinetic (PK) and pharmacodynamic (PD) profiles of natalizumab in pediatric patients with relapsing-remitting MS (RRMS)

Correction to: Cognitive assessment in multiple sclerosis—an Italian consensus

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Transperitoneal laparoscopic retrievement of a migrated prosthetic head after total hip arthroplasty: a case report

The migration of a prosthetic head during total hip arthroplasty (THA) is a rare complication. Few cases are described in the literature, offering different solutions and surgical approaches for prosthetic head retrievement. Here, we present a case of successful laparoscopic transperitoneal retrieval of a prosthetic head migrated above the right iliac vein after THA with a posterolateral approach

A Comprehensive Review on Copemyl(\uae)

Economic sustainability is of paramount importance in the rapidly evolving therapeutic scenario of multiple sclerosis (MS). Glatiramoids are a class of drugs whose forefather, glatiramer acetate, has been used as a disease modifying drug (DMD) in patients with MS for over 20&nbsp;years. Its patent expired in 2015; new versions of such drug are nowadays available on the market, potentially contributing to lowering prices and enhancing a better allocation of economic resources. In this review, we analyze the recommendations underlying the approval of both generic drugs and biosimilars by regulatory authorities, and we provide methodological tools to contextualize the design of studies on these new classes of drugs. We examine in more detail the preclinical and clinical data of Copemyl(\uae), a new member of the glatiramoid class, focusing on its biological and immunological properties and illustrating randomized controlled trials that led to its authorization

Effect of fingolimod on health-related quality of life in paediatric patients with multiple sclerosis: results from the phase 3 PARADIG MS Study

Background In the PARADIG MS Study, fingolimod demonstrated superior efficacy versus interferon (IFN) β-1a and comparable overall incidence of adverse events but slightly higher rate of serious adverse events in patients with paediatric-onset multiple sclerosis (PoMS). Here, we report the health-related quality of life (HRQoL) outcomes from PARADIG MS . Methods Patients with PoMS (N=215; aged 10–<18 years) were randomised to once-daily oral fingolimod (N=107) or once-weekly intramuscular IFN β-1a (N=108). HRQoL outcomes were assessed using the 23-item Pediatric Quality of Life (PedsQL) scale that comprises Physical and Psychosocial Health Summary Scores (including Emotional, Social and School Functioning). A post hoc inferential analysis evaluated changes in self-reported or parent-reported PedsQL scores from baseline up to 2 years between treatment groups using an analysis of covariance model. Results Treatment with fingolimod showed improvements versus IFN β-1a on the PedsQL scale in both the self-reported and parent-reported Total Scale Scores (4.66 vs −1.16, p≤0.001 and 2.71 vs −1.02, p≤0.05, respectively). The proportion of patients achieving a clinically meaningful improvement in the PedsQL Total Scale Score was two times higher with fingolimod versus IFN β-1a per the self-reported scores (47.5% vs 24.2%, p=0.001), and fingolimod was favoured versus IFN β-1a per the parent-reported scores (37.8% vs 24.7%, p=non-significant). Group differences in self-reported Total Scale Scores in favour of fingolimod were most pronounced among patients who had ≥2 relapses in the year prior to study entry or who showed improving or stable Expanded Disability Status Scale scores during the study. Conclusion Fingolimod improved HRQoL compared with IFN β-1a in patients with PoMS as evidenced by the self-reported and parent-reported PedsQL scores

Subcutaneous interferon β-1a in pediatric patients with multiple sclerosis: Regional differences in clinical features, disease management, and treatment outcomes in an international retrospective study

AbstractBackgroundTo further understand management of pediatric patients with multiple sclerosis (MS), we examined disease features, clinical practice patterns, and response to treatment in the United States (US) and seven other countries ('rest of World'; ROW).MethodsAnonymized data, recorded as part of routine clinical practice, were obtained from medical records (1997–2009) of study participants (who received subcutaneous interferon β-1a before age 18years) from the US and ROW. Samples were stratified by age (preadolescents [<12years] and adolescents [12–17years]).ResultsUS adolescents had a higher mean body mass index versus ROW adolescents (BMI; 27.2 versus 22.5kg/m2), started disease-modifying therapy (DMT) earlier after the first relapse, were more likely to have received a DMT before initiating subcutaneous interferon β-1a, had a higher relapse rate, and were more likely to switch from subcutaneous interferon β-1a to another DMT before the end of the observation period.ConclusionsThis retrospective analysis of a multinational sample of pediatric MS patients who received subcutaneous interferon β-1a found that those from the US had higher BMI, relapsed more frequently, and were managed differently, compared with ROW patients. Future prospective studies are needed to confirm these observations and ascertain their clinical significance