Spasticity in practice (SPACE): an international non-interventional study of botulinum neurotoxin type A in treatment-naïve subjects with spasticity.

AIM OF THE STUDY: SPACE, a prospective, non-interventional, open-label, multinational study, investigated physicians' and subjects' assessment of safety, efficacy, and health-related quality of life (HRQoL) following botulinum neurotoxin type A (BoNT-A) treatment to understand real-world clinical usage for the management of focal and multifocal spasticity. CLINICAL RATIONALE FOR THE STUDY: Treatment guidelines recommend the use of BoNT-A for the management of spasticity in adults. This study assessed how physicians use BoNT-A therapy in real-world clinical practice, and provided evidence on long-term safety and efficacy over a period of up to 2 years. MATERIALS AND METHODS: BoNT treatment-naïve adults with spasticity of any aetiology received any BoNT-A formulation at their physician's discretion, and were observed for ≤ 8 treatment cycles (≤ 2 years). Daily practice information, physician's global assessments of tolerability and efficacy, and HRQoL were documented. Incidences of adverse drug reactions or all adverse events were documented for non-Mexican subjects and for Mexican subjects, respectively, due to protocol differences based on local regulatory requirements. RESULTS: A total of 701 subjects were enrolled (safety population; nine countries). Physicians rated the tolerability of BoNT-A as 'very good' or 'good' for 88.2-97.4% of subjects throughout the study (subject numbers declined throughout this non-interventional study). Adverse drug reactions were reported for 16/600 (2.7%) of the non-Mexican subjects, with two considered to be 'definitely related' to treatment (injection-site haematoma, n = 1; botulism, n = 1). For 687 subjects, efficacy was rated 'very good' or 'good' by most physicians and subjects. Improvements in HRQoL were observed. CONCLUSIONS AND CLINICAL IMPLICATIONS: Throughout this 2-year study, BoNT-A treatment was generally well-tolerated, effective, and associated with an improved HRQoL. This study makes a valuable contribution to the broader understanding of how physicians use BoNT-A therapy to manage spasticity in real-world clinical practice.

Integration of spoken and written words in beginning readers: a topographic ERP study.

Integrating visual and auditory language information is critical for reading. Suppression and congruency effects in audiovisual paradigms with letters and speech sounds have provided information about low-level mechanisms of grapheme-phoneme integration during reading. However, the central question about how such processes relate to reading entire words remains unexplored. Using ERPs, we investigated whether audiovisual integration occurs for words already in beginning readers, and if so, whether this integration is reflected by differences in map strength or topography (aim 1); and moreover, whether such integration is associated with reading fluency (aim 2). A 128-channel EEG was recorded while 69 monolingual (Swiss)-German speaking first-graders performed a detection task with rare targets. Stimuli were presented in blocks either auditorily (A), visually (V) or audiovisually (matching: AVM; nonmatching: AVN). Corresponding ERPs were computed, and unimodal ERPs summated (A + V = sumAV). We applied TANOVAs to identify time windows with significant integration effects: suppression (sumAV-AVM) and congruency (AVN-AVM). They were further characterized using GFP and 3D-centroid analyses, and significant effects were correlated with reading fluency. The results suggest that audiovisual suppression effects occur for familiar German and unfamiliar English words, whereas audiovisual congruency effects can be found only for familiar German words, probably due to lexical-semantic processes involved. Moreover, congruency effects were characterized by topographic differences, indicating that different sources are active during processing of congruent compared to incongruent audiovisual words. Furthermore, no clear associations between audiovisual integration and reading fluency were found. The degree to which such associations develop in beginning readers remains open to further investigation.

Comparison of basal insulin added to oral agents versus twice-daily premixed insulin as initial insulin therapy for type 2 diabetes.

OBJECTIVE: To compare the efficacy and safety of adding once-daily basal insulin versus switching to twice-daily premixed insulin in type 2 diabetic patients insufficiently controlled by oral antidiabetic agents (OADs). RESEARCH DESIGN AND METHODS: In a 24-week, multinational, multicenter, open, parallel group clinical trial, 371 insulin-naive patients with poor glycemic control (fasting blood glucose [FBG] >/=120 mg/dl, HbA(1c) 7.5-10.5%) on OADs (sulfonylurea plus metformin) were randomized to once-daily morning insulin glargine plus glimepiride and metformin (glargine plus OAD) or to 30% regular/70% human NPH insulin (70/30) twice daily without OADs. Insulin dosage was titrated to target FBG