Spinal muscular atrophy is a rare, autosomal recessive, neuromuscular disease caused by biallelic loss of the survival motor neuron 1 (SMN1) gene, resulting in motor neuron dysfunction. In this ...STR1VE-EU study, we aimed to evaluate the safety and efficacy of onasemnogene abeparvovec gene replacement therapy in infants with spinal muscular atrophy type 1, using broader eligibility criteria than those used in STR1VE-US.
STR1VE-EU was a multicentre, single-arm, single-dose, open-label phase 3 trial done at nine sites (hospitals and universities) in Italy (n=4), the UK (n=2), Belgium (n=2), and France (n=1). We enrolled patients younger than 6 months (180 days) with spinal muscular atrophy type 1 and the common biallelic pathogenic SMN1 exon 7–8 deletion or point mutations, and one or two copies of SMN2. Patients received a one-time intravenous infusion of onasemnogene abeparvovec (1·1 × 1014 vector genomes vg/kg). The outpatient follow-up consisted of assessments once per week starting at day 7 post-infusion for 4 weeks and then once per month until the end of the study (at age 18 months or early termination). The primary outcome was independent sitting for at least 10 s, as defined by the WHO Multicentre Growth Reference Study, at any visit up to the 18 months of age study visit, measured in the intention-to-treat population. Efficacy was compared with the Pediatric Neuromuscular Clinical Research (PNCR) natural history cohort. This trial is registered with ClinicalTrials.gov, NCT03461289 (completed).
From Aug 16, 2018, to Sept 11, 2020, 41 patients with spinal muscular atrophy were assessed for eligibility. The median age at onasemnogene abeparvovec dosing was 4·1 months (IQR 3·0–5·2). 32 (97%) of 33 patients completed the study and were included in the ITT population (one patient was excluded despite completing the study because of dosing at 181 days). 14 (44%, 97·5% CI 26–100) of 32 patients achieved the primary endpoint of functional independent sitting for at least 10 s at any visit up to the 18 months of age study visit (vs 0 of 23 untreated patients in the PNCR cohort; p<0·0001). 31 (97%, 95% CI 91–100) of 32 patients in the ITT population survived free from permanent ventilatory support at 14 months compared with six (26%, 8–44) of 23 patients in the PNCR natural history cohort (p<0·0001). 32 (97%) of 33 patients had at least one adverse event and six (18%) had adverse events that were considered serious and related to onasemnogene abeparvovec. The most common adverse events were pyrexia (22 67% of 33), upper respiratory infection (11 33%), and increased alanine aminotransferase (nine 27%). One death, unrelated to the study drug, occurred from hypoxic-ischaemic brain damage because of a respiratory tract infection during the study.
STR1VE-EU showed efficacy of onasemnogene abeparvovec in infants with symptomatic spinal muscular atrophy type 1. No new safety signals were identified, but further studies are needed to show long-term safety. The benefit–risk profile of onasemnogene abeparvovec seems favourable for this patient population, including those with severe disease at baseline.
Novartis Gene Therapies.
Abstract Introduction The Dissociative Experiences Scale (DES) is a widely used instrument for assessing dissociation. However, there is disagreement regarding the internal structure of the DES and ...scores tend to be highly skewed. Objective The present study was designed to test the psychometric properties of a French version of the DES in non-clinical participants, in addition to applying a response scale as recommended by Wright and Loftus (1999) in order to resolve the problem of skewed scores. Results Exploratory and confirmatory factor analysis (computed in two independent samples) suggested a two-factor solution, which seem to represent two forms of dissociation (“automatic pilot” related dissociation episodes and “defensive” dissociation episodes). Results also revealed high internal consistency, and satisfactory results in terms of skewness and floor effects. Finally, significant associations with other measures (anxiety, depression, traumatic experiences) indicate good concurrent validity. Conclusions This study offers evidence that the present version of the French adaptation of the DES reveals good psychometric properties. Analyses of the internal structure of the DES suggest that two types of dissociative experiences are being measured: automatic pilot-related dissociation episodes (e.g., associated with different types of cognitive failures) and defensive dissociation episodes that may act as defensive mechanisms, especially in persons who have been traumatized (e.g., the avoidance of a memory related to a traumatic event).
Qualitative characteristics of cryptomnesia, or unintentional plagiarism were investigated. In Experiment 1 we compared accurate and inaccurate source attributions in terms of their level of ...confidence using instructions that did not require a fixed number of responses. Confidence was lower for plagiarised responses than for correct responses. Nevertheless, participants provided high ratings of certainty for a large proportion of their plagiarised responses. In Experiment 2 the phenomenological differences between plagiarised recall and veridical recall were compared by using an adaptation of the memory characteristics questionnaire (Johnson, Foley, Suengas, & Raye, 1988). Correct responses were associated with more experiential detail than plagiarised responses. However, a considerable number of plagiarised responses were accompanied by a confident memory of at least one qualitative characteristic. Results are discussed in terms of the source monitoring framework developed by Johnson, Hashtroudi, and Lindsay (1993).
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BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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