Sativex® (nabiximols) cannabinoid oromucosal spray in patients with resistant multiple sclerosis spasticity: the Belgian experience.

BACKGROUND: This retrospective study evaluates patient-reported outcomes in patients with multiple sclerosis (MS) spasticity who were treated with a cannabinoid oromucosal spray (Sativex®, USAN name: nabiximols) after not sufficiently responding to previous anti-spasticity medications. METHODS: Of 276 patients from eight centers in Belgium who began treatment prior to 31 December 2017, effectiveness assessment data were available for 238 patients during the test period of 4 to 8/12 weeks, and for smaller patient cohorts with continued treatment for 6/12 months. RESULTS: Mean 0-10 spasticity Numerical Rating Scale (NRS) scores improved from 8.1 at baseline to 5.2 (week 4), 4.6 (week 8) and 4.1 (week 12). Mean EuroQoL Visual Analogue Scale (EQ VAS) scores increased from 39 at baseline to 52 (week 4), 57 (week 8) and 59 (week 12). Mean NRS and EQ VAS scores remained in the same 12 weeks' range in patients with longer-term data. The average dose of cannabinoid oromucosal spray was 6 sprays/day. Most of the 93 out of 276 patients, with initial prescription (33.7%), who discontinued treatment by week 12 did so within the first 8 weeks, mainly due to lack of effectiveness. By week 12, 171 (74%) of the 230 effectiveness evaluable patients reported a clinically meaningful response, corresponding to ≥30% NRS improvement. The tolerability of cannabinoid oromucosal spray was consistent with its known safety profile. CONCLUSIONS: More than 60% of the patients with MS who started add-on treatment with cannabinoid oromucosal spray reported a clinically relevant symptomatic effect and continued treatment after 12 weeks.

Effects of moderate amounts of barley in late pregnancy on growth, glucose metabolism and osteoarticular status of pre-weaning horses.

In stud management, broodmares are commonly fed concentrates in late pregnancy. This practice, however, was shown to correlate with an increased incidence of osteochondrosis in foals, which may be related to insulin sensitivity. We hypothesized that supplementation of the mare with barley in the last trimester of pregnancy alters the pre-weaning foal growth, glucose metabolism and osteoarticular status. Here, pregnant multiparous saddlebred mares were fed forage only (group F, n=13) or both forage and cracked barley (group B, n=12) from the 7th month of pregnancy until term, as calculated to cover nutritional needs of broodmares. Diets were given in two daily meals. All mares and foals returned to pasture after parturition. Post-natal growth, glucose metabolism and osteoarticular status were investigated in pre-weaning foals. B mares maintained an optimal body condition score (>3.5), whereas that of F mares decreased and remained low (<2.5) up to 3 months of lactation, with a significantly lower bodyweight (-7%) than B mares throughout the last 2 months of pregnancy. B mares had increased plasma glucose and insulin after the first meal and after the second meal to a lesser extent, which was not observed in F mares. B mares also had increased insulin secretion during an intravenous glucose tolerance test (IVGTT). Plasma NEFA and leptin were only temporarily affected by diet in mares during pregnancy or in early lactation. Neonatal B foals had increased serum osteocalcin and slightly increased glucose increments and clearance after glucose injection, but these effects had vanished at weaning. Body measurements, plasma IGF-1, T4, T3, NEFA and leptin concentrations, insulin secretion during IVGTT, as well as glucose metabolism rate during euglycemic hyperinsulinemic clamps after weaning, did not differ between groups. Radiographic examination of joints indicated increased osteochondrosis relative risk in B foals, but this was not significant. These data demonstrate that B or F maternal nutrition has very few effects on foal growth, endocrinology and glucose homeostasis until weaning, but may induce cartilage lesions.

Cognitive performance in relapsing remitting multiple sclerosis: a longitudinal study in daily practice using a brief computerized cognitive battery.

BACKGROUND: There is need for a cognitive test battery that can be easily used in clinical practice to detect or monitor cognitive performance in patients with multiple sclerosis (MS). In order to conduct, in this patient group, a preliminary investigation of the validity and utility of a brief computerized battery, the Cognitive Drug Research (CDR) battery, we longitudinally assessed cognition in patients with relapsing remitting (RR) MS. METHODS: Forty-three mildly disabled, clinically active RRMS patients were repeatedly assessed with the Digit Symbol Substitution Test (DSST), Paced Auditory Serial Addition Test (PASAT) and five composite scores derived from the CDR computerized cognitive test system (CDR System): Power of Attention, Continuity of Attention, Quality of Working Memory, Quality of Episodic Memory and Speed of Memory. The Multiple Sclerosis Functional Composite (MSFC) and Expanded Disability Status Scale (EDSS) measured disability. RESULTS: The composite scores from the CDR battery generally showed excellent test-retest reliability over the repeated assessments, though was low on occasions for the Quality of Working Memory and Quality of Episodic Memory measures. The CDR measures tended to be highly correlated with other measures of cognition (DSST and PASAT) and were also strongly related to disability (EDSS and MSFC). Baseline scores indicated large impairments to visual information processing speed and attention (DSST, Cohen's d 1.1; Power of Attention d 1.4 [reaction time on tasks of focussed and sustained attention]), and a moderate impairment both to sustained attention (Continuity of Attention d 0.6) and complex information processing speed (Speed of memory d 0.7 [reaction time on tasks of working and episodic Memory]), when compared to normative data derived from healthy volunteers enrolled in a series of separate, prior clinical trials. Working memory (Quality of Working Memory) and episodic memory (Quality of Episodic Memory) were unimpaired. CONCLUSIONS: Preliminary validation of the CDR System indicated that for most, but not all measures psychometric properties were adequate and the measures were related to disability (EDSS and MSFC) and other measures of cognition.

Effect of PUFA on embryo cryoresistance, gene expression and AMPKalpha phosphorylation in IVF-derived bovine embryos.

The objectives of the present study were to evaluate the effect of conjugated linoleic acid (CLA t10, c12, C18:2), linolenic acid (C18:3) and docosahexaenoic acid (DHA, C22:6) supplementation on in vitro bovine embryo development, embryo survival after cryopreservation, gene expression and AMPKalpha phosphorylation. Control groups with modified synthetic oviduct fluid (mSOF)+/-100microM beta-mercaptoethanol (beta-ME) were performed. The effects of co-culture with bovine oviduct epithelial cell (Boec) monolayers, serum supplementation and embryo development in the ewe oviduct, on gene expression were also examined. Experiments 1 and 2: a lower d 7 embryo survival was found with 100microM C22:6 and 100microM C18:2 supplementation compared to 1microM C22:6 and 100microM beta-ME supplementation (P<0.05). C18:3 supplementation had no effect on d 7 embryo survival, but 100microM C18:3 increased d 8 embryo survival compared to 100microM beta-ME supplementation (P<0.05). Experiments 3 and 4: stearoyl-CoA desaturase 1 (SCD1) and sterol regulatory element-binding transcription factor 1 (SREBP1) mRNA decreased after 10microM C22:6 supplementation compared to all other supplementations (P<0.05). A lower fatty acid desaturase 2 (FADS2) transcript level was found with 100microM C18:2, 10microM C22:6 and 10microM C18:3 supplementations compared to groups without fatty acid supplementation (P<0.05). Acetyl-CoA-carboxylase (ACC), fatty acid synthase (FAS), adipose differentiation-related protein (ADRP), acyl-CoA synthetase long-chain family member 1 (ACSL1), diacylglycerol O-acyltransferase 1 (DGAT1), carnitin palmitoyltransferase-II (CPT-II) mRNAs expression and AMPKalpha phosphorylation were not modified with PUFA supplementation. Experiment 5: SCD1 and FAS mRNA decrease in Boec group compared to serum supplementation, as SCD1 mRNA in ewe oviduct group (P<0.05). In conclusion, this study showed that a PUFA supplementation with C18:2, C18:3 or C22:6 in bovine culture development for 6 days and co-culture with Boec down-regulate mRNA expression of proteins involved in lipid metabolism in d 7-8 embryo (SCD1 and FADS2 desaturases), probably through SREBP1 mRNA regulation after 10microM C22:6 supplementation, indicating a modification of saturated/unsaturated fatty acid balance in bovine blastocyst.