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To evaluate the influence ofantiplatelet drugs on patency in femoropopliteal vein bypasses, 48 vascular surgeons recruited 549 patients to a randomized double-blind trial of aspirin (300 rag) + dipyridamole (150 rag) or placebo twice daily starting 2 days before surgery and continuing indefinitely. Graft occlusion measured objectively by independent coordinators and cardiovascular events (myocardial infarction or stroke) were studied, expressed by life table, and analyzed statistically by log rank and confidence intervals (95% CI). Randomization achieved comparable groups with 60% of grafts inserted for rest pain or gangrene. Operative complications on aspirin plus dipyridamole included 18 reoperations for bleeding and 12 hematomas compared with 9 and 14, respectively, on placebo (NS). Most of the 172 graft failures occurred early with failure rates of 43/1000 patient-months in the first 3 months, reducing to 17/1000 at 6 to 12 months, and under 10/1000 in subsequent years. Cumulative graft patency on placebo was 72%, 62%, and 60% at 1, 2, and 3 years, respectively, compared with 78%, 70%, and 61% on aspirin plus dipyridamole. The difference in patency of 6.1% (95% CI,-3% to 15.5%) at 1 year and 8.0% (95% CI,-5% to 21%) at 2 years failed to achieve significance (p = 0.43). On mean follow-up of 34 months, 53 (132/1000 patient-years) cardiovascular events (myocardial infarction or cerebrovascular accident) occurred in patients on placebo compared with only 35 (73/1000) on aspirin plus dipyridamole, a significant difference of 59/1000 (p = 0.004). Antiplatelet therapy had little influence on femoropopliteal vein patency, but subsequent myocardial infarction and stroke was reduced in these patients with peripheral vascular disease.

Objective: To assess the benefits and harms of cannabis-based products for pediatric epilepsy. Methods: We identified in this living systematic review randomized controlled trials (RCTs) and nonrandomized studies (NRSs) involving children with epilepsy treated with cannabis-based products. We searched MEDLINE, Embase, Psy-cINFO, Cochrane Library, and gray literature (April 25, 2018). The primary outcome was seizure freedom; secondary outcomes were seizure frequency (total, ≥50% reduction), quality of life, sleep, status epilepticus, death, gastrointestinal adverse events, and visits to the emergency room. Data were pooled by randomeffects meta-analysis. Risk of bias was assessed for each study, and GRADE was used to assess the quality of evidence for each outcome. Results: Four RCTs and 19 NRSs were included, primarily involving cannabidiol.All RCTs were at low risk of bias, whereas all NRSs were at high risk. Among RCTs, there was no statistically significant difference between cannabidiol and placebo in seizure freedom (relative risk [RR] = 6.77, 95% confidence interval [CI] = 0.36-128.38; 1 RCT), quality of life (mean difference = 0.6, 95% CI = −2.6 to 3.9; 3 RCTs), sleep disruption (mean difference = −0.3, 95% CI = −0.8 to 0.2; 3 RCTs), or vomiting (RR = 1.00, 95% CI = 0.51-1.96; 4 RCTs). There was a statistically significant reduction in the median frequency of monthly seizures with cannabidiol compared with placebo (−19.8%, 95% CI = −27.0% to −12.6%; 3 RCTs) and an increase in the number of participants with at least a 50% reduction in seizures (RR = 1.76, 95% CI = 1.07-2.88; 1 RCT) and diarrhea (RR = 2.25, 95% CI = 1.38-3.68; 3 RCTs). Death and status epilepticus were infrequently reported. Significance: Evidence from high-quality RCTs suggests that cannabidiol probably reduces seizures among children with drug-resistant epilepsy (moderate certainty). At this time, the evidence base is primarily limited to cannabidiol, and these findings should not be extended to all cannabis-based products. K E Y W O R D S cannabidiol, cannabis, efficacy, pediatric drug-resistant epilepsy, safety, seizure, systematic review PROSPERO: CRD42018084755

This paper describes the relative simplicity of 35 black and white patterns. Although each pattern is made of three black squares and four white squares, the patterns are different, and not all equally easy to perceive, conceive, remember, distinguish or describe.We present four experiments. The first experiment determines which of the patterns can be found most quickly from a collection of patterns. The second experiment determines which of the patterns seem simplest to someone looking at them. The third experiment determines which of the patterns people find easiest to remember, and also which of the patterns are most likely to be confused with others. The fourth experiment determines which of the patterns are easiest to describe in words. Each of these experiments, then, defines an empirical measure of simplicity; and the third experiment defines two such measures. Each measure generates a rank order of simplicity on the 35 patterns. The experiments therefore generate five such rank orders.There are two reasons for describing these rank orders. First, it turns out that the five rank orders are almost identical. One may, therefore, talk about the simplicity order of the patterns, and treat this rank order as a basic empirical fact about the cognition of these patterns. Second, this underlying simplicity order raises the question: "What stimulus properties are responsible for differences in cognitive simplicity?" The central result of this paper is this: The cognitive simplicity of the 35 patterns is almost perfectly accounted for by the relative numbers of subsymmetries in the different patterns. EXPERIMENTAL PROCEDURE MaterialsThe stimulus materials used in these experiments are the same as those described in Alexander and Huggins (1964). There are 35 patterns, each printed on a strip of paper 2-5/8 in. long and 3/8 in. high. Each pattern is, in effect, a horizontal linear arrangement of three black and four white squares, but adjacacent squares of the same color are not separated. Along the bottom edge of the pattern there is a thin grey line, which orients the pattern, and keeps mirror-image patterns distinct. There are just 35 different possible arrangements of this kind (7!/3!.4!), and each of these possible arrangements appears just once among the 35 stimuli. To keep figure-group relationships constant during the experiments, the patterns were always seen against the same achromatic grey, chosen so that neither the black nor the white seemed to stand out more strongly than the other. The patterns are illustrated in Fig. I. They are shown in the order of simplicity determined by the five experiments.Two random-like arrays of all 35 patterns, called R2 and R3, were used. Each of these random-like arrays is a rectangular block of patterns, five by seven, the patterns arranged in such a way that there is no discernible rule or regularity governing their positions, with adjacent patterns far enough apart to prevent visual interference. Since the position of a pattern in an array can make it easier to find, or...

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AIMTo investigate the efficacy of a chitosan/polyethylene glycol blended paste as a local antibiotic delivery device, particularly in musculoskeletal wounds.METHODSAcidic (A) chitosan sponges and neutralized (N) chitosan/polyethylene glycol (PEG) blended sponges were combined in ratios of 3A:2N, 1A:1N, and 2A:3N; then hydrated with phosphate buffered saline to form a chitosan/PEG paste (CPP). Both in vitro and in vivo studies were conducted to determine the potential CPP has as a local antibiotic delivery device. In vitro biocompatibility was assessed by the cytotoxic response of fibroblast cells exposed to the experimental groups. Degradation rate was measured as the change in dry mass due to lysozyme based degradation over a 10-d period. The antibiotic elution profiles and eluate activity of CPP were evaluated over a 72-h period. To assess the in vivo antimicrobial efficacy of the CPP, antibiotic-loaded paste samples were exposed to subcutaneously implanted murine catheters inoculated with Staphylococcus aureus. Material properties of the experimental paste groups were evaluated by testing the ejection force from a syringe, as well as the adhesion to representative musculoskeletal tissue samples.RESULTSThe highly acidic CPP group, 3A:2N, displayed significantly lower cell viability than the control sponge group. The equally distributed group, 1A:1N, and the highly neutral group, 2A:3N, displayed similar cell viability to the control sponge group and are deemed biocompatible. The degradation studies revealed CPP is more readily degradable than the chitosan sponge control group. The antibiotic activity studies indicated the CPP groups released antibiotics at a constant rate and remained above the minimum inhibitory concentrations of the respective test bacteria for a longer time period than the control chitosan sponges, as well as displaying a minimized burst release. The in vivo functional model resulted in complete bacterial infection prevention in all catheters treated with the antibiotic loaded CPP samples. All experimental paste groups exhibited injectability and adhesive qualities that could be advantageous material properties for drug delivery to musculoskeletal injuries.CONCLUSIONCPP is an injectable, bioadhesive, biodegradable, and biocompatible material with potential to allow variable antibiotic loading and active, local antibiotic release to prevent bacterial contamination.