Practical and clinical utility of non-invasive vagus nerve stimulation (nVNS) for the acute treatment of migraine. A post hoc analysis of the randomized, sham-controlled, double-blind PRESTO trial

Background: The PRESTO study of non-invasive vagus nerve stimulation (nVNS; gammaCore®) featured key primary and secondary end points recommended by the International Headache Society to provide Class I evidence that for patients with an episodic migraine, nVNS significantly increases the probability of having mild pain or being pain-free 2 h post stimulation. Here, we examined additional data from PRESTO to provide further insights into the practical utility of nVNS by evaluating its ability to consistently deliver clinically meaningful improvements in pain intensity while reducing the need for rescue medication. Methods: Patients recorded pain intensity for treated migraine attacks on a 4-point scale. Data were examined to compare nVNS and sham with regard to the percentage of patients who benefited by at least 1 point in pain intensity. We also assessed the percentage of attacks that required rescue medication and pain-free rates stratified by pain intensity at treatment initiation. Results: A significantly higher percentage of patients who used acute nVNS treatment (n = 120) vs sham (n = 123) reported a ≥ 1-point decrease in pain intensity at 30 min (nVNS, 32.2%; sham, 18.5%; P = 0.020), 60 min (nVNS, 38.8%; sham, 24.0%; P = 0.017), and 120 min (nVNS, 46.8%; sham, 26.2%; P = 0.002) after the first attack. Similar significant results were seen when assessing the benefit in all attacks. The proportion of patients who did not require rescue medication was significantly higher with nVNS than with sham for the first attack (nVNS, 59.3%; sham, 41.9%; P = 0.013) and all attacks (nVNS, 52.3%; sham, 37.3%; P = 0.008). When initial pain intensity was mild, the percentage of patients with no pain after treatment was significantly higher with nVNS than with sham at 60 min (all attacks: nVNS, 37.0%; sham, 21.2%; P = 0.025) and 120 min (first attack: nVNS, 50.0%; sham, 25.0%; P = 0.018; all attacks: nVNS, 46.7%; sham, 30.1%; P = 0.037). Conclusions: This post hoc analysis demonstrated that acute nVNS treatment quickly and consistently reduced pain intensity while decreasing rescue medication use. These clinical benefits provide guidance in the optimal use of nVNS in everyday practice, which can potentially reduce use of acute pharmacologic medications and their associated adverse events. Trial registration: ClinicalTrials.gov identifier: NCT02686034

Effects of N fertilizers and rates on yield, safety and nutrients in processing spinach genotypes

Two field experiments were carried out at the Experimental Field, Department of Food Science (TE, Italy) in 2004 and 2005 to evaluate the effects of genotypes, different N forms and N rates on yield, safety and nutritional features of processing spinach. Experiment 1, as treatments, included spinach genotypes and N forms (CO(NH2)2; Agricote; NH4NO3); experiment 2 included three N forms (Ca(NO3)2; (NH4)2SO4; NH4NO3) applied at rates of 0, 75, 150, 200 kg N ha1. This research work confirmed differences among spinach genotypes in terms of efficiency in N use and oxalate and nitrate accumulation. Spinach accumulated much more nitrate in petioles and much more oxalate in blades indicating that nitrate and oxalate might play a counterrole to each other. Fertilizers containing N under forms not readily available to the crop, i.e. Agricote, CO(NH2)2 and (NH4)2SO4, increased nitrate and oxalate accumulations less than fast N-release fertilizers, but their effect on yield was limited. Highest yield with contents of nitrate and oxalate lower than the limits imposed to avoid health problems, were achieved with Ca(NO3)2, at rates of 130 and 150 kg N ha1 NH4NO3. A good accumulation in some important macronutrients for the human diet such as Ca, K and P were allowed by application of Ca(NO3)2, at rates of 130 and 150 kg N ha1 NH4NO3. The glucose, fructose, sucrose as well as Mg accumulation were not alterable in spinach with nitrogen fertilization or with genotype choice