ATG‐Fresenius Treatment and Low‐Dose Tacrolimus: Results of a Randomized Controlled Trial in Liver Transplantation

We report the results of a prospective randomized controlled trial in liver transplantation assessing the efficacy and safety of antithymocyte globulin (ATG‐Fresenius) plus tacrolimus monotherapy at gradually decreasing doses. Patients were randomized to either: (a) standard‐dose tacrolimus plus steroids;or (b) peritransplant ATG‐Fresenius plus reduced‐dose tacrolimus monotherapy followed by weaning of tacrolimus starting 3 months after transplantation. The primary end‐point was the achievement of very low‐dose tacrolimus (every‐other‐day or once daily dose with <5 ng/mL trough levels) at 12 months after transplantation. Acute rejection occurring during the first 3 months after transplantation was more frequent in the ATG group (52.4% vs. 25%). Moreover, late acute rejection episodes occurred in all recipients in whom weaning was attempted and no recipients reached the primary end‐point. This motivated the premature termination of the trial. Tacrolimus trough levels were lower in the ATG‐Fresenius group but no benefits in terms of improved renal function, lower metabolic complications or increased prevalence of tolerance‐related biomarkers were observed. In conclusion, the use of ATG‐Fresenius and tacrolimus at gradually decreasing doses was associated with a high rate of rejection, did not allow for the administration of very low doses of tacrolimus and failed to provide detectable clinical benefits. ClinicalTrials.gov identifier:NCT00436722.     

Glucose and lipid metabolism of long-term risperidone monotherapy in patients with schizophrenia

Risperidone has a relatively low risk of causing obesity and diabetes mellitus and is a first-line treatment for schizophrenia. The aim of the present study was to investigate glucose and lipid metabolism, and feeding-control parameters in schizophrenia patients treated with long-term risperidone monotherapy. Fifteen patients with paranoid-type schizophrenia who had been treated with risperidone and had Global Assessment of Function (GAF) scores >70 were selected and compared with healthy volunteers (n = 25). Single assessments of psychotic symptoms, side-effects, Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) score, bodyweight, body fat percentage and blood sampling were performed. Fasting blood glucose, insulin, hemoglobin A1c, homeostasis model assessment insulin resistance index (HOMA-IR), total cholesterol, triglyceride, high density lipoprotein (HDL)-, low density lipoprotein-cholesterol, adiponectin, prolactin and feeding-control parameters (ghrelin and leptin) were analyzed. The body fat percentage (P = 0.0018), body mass index (BMI) (P = 0.0150), fasting blood glucose (P = 0.0358), triglyceride (P = 0.0377), leptin (P = 0.0243), total ghrelin (P = 0.0067), active ghrelin (P = 0.0241) and prolactin (P < 0.0001) levels of patients treated with risperidone were significantly higher than those of healthy volunteers, while the HDL-cholesterol level (P = 0.0222) was significantly lower. Although the patients had very mild psychiatric symptoms and maintained functionally high levels, the glucose and lipid parameters were significantly impaired compared to healthy volunteers. A high level of plasma ghrelin might increase appetite, leading to exacerbation of metabolic impairment.     

Efficacy and tolerability of coadministration of rizatriptan and acetaminophen vs rizatriptan or acetaminophen alone for acute migraine treatment

Objective.— To evaluate the efficacy and tolerability of coadministration of rizatriptan and acetaminophen in the acute treatment of migraine.
Background.— Rizatriptan is a selective 5-HT_1B/1D agonist approved for the acute treatment of migraine. Acetaminophen has been studied for acute migraine treatment. In consideration of the prominent central and peripheral mechanisms in migraine, the use of "multi-mechanism therapy" is gaining momentum in the treatment of acute migraine attacks.
Study Design.— This was a randomized, double-blind, placebo-controlled trial conducted at 10 centers. Eligible patients with migraine according to International Headache Society criteria treated a single migraine attack of moderate or severe intensity within 4 h from pain onset. Patients were randomized into 1 of 4 groups (rizatriptan 10 mg + acetaminophen 1000 mg [RA], rizatriptan alone [R], acetaminophen alone [A], and placebo [P]). There were 3 co-primary hypotheses tested sequentially for 2-h pain relief: (1) RA would be superior to P; (2) if the first was fulfilled, RA would be superior to A; and (3) if the first 2 were fulfilled, RA would be superior to R.
Results.— Of 173 patients who treated a migraine, 123 patients (71.5%) achieved pain relief within 2 h. RA (90%) was significantly better than P (46%) and A (70%), but only numerically better than R (77%) for 2-h pain relief. No significant differences were seen between the active treatment groups in adverse events.
Conclusion.— Rizatriptan coadministered with acetaminophen achieved 2 of the 3 primary hypotheses, proving superior to both acetaminophen and placebo for 2-h pain relief, but failing to achieve superiority to rizatriptan alone. RA was as well tolerated as each of the individual agents.     

左乙拉西坦单药治疗各类癫痈的疗效

左乙拉西坦是一种新型作用机制的抗癫痫药物,其抗痢机制可能是通过影响突触囊泡蛋白SV2A来实现。本文就该药物单一治疗各类癫痫（新诊断癫痫、部分性发作、全面性发作及手术后癫痫等）的疗效和耐受性研究做介绍。     

The efficacy and tolerability of lamotrigine adjunctive/ monotherapy in patients with partial seizures refractory to poly-AEDs

Objective: This study was designed as an open-label trial to assess the effects of changing the antiepileptic drugs (AEDs) regi-men to lamotrigine (LTG) as adjunctive/monotherapy in patients with partial seizures who were dissatisfied with their drug regimen because of intractable seizures. Methods: The patients were recruited from multicenters using the following criteria: age≥18 years; at least 3 seizures per month during the last 16 weeks; previous use of at least 3 AEDs. The study involved a baseline phase and 2 experimental phases: LTG was first added to the regimen, and then patients could gradually change to LTG monotherapy if their seizures were reduced by at least 50 percent/month. Tolerability, the primary end point, was assessed using the Liverpool Adverse Experience Profile (LAEP). Secondary end points included quality of life, as measured with the Quality of Life in Epilepsy-31 inven-tory. Reductions in seizures from baseline throughout each phase were also analyzed. Results: One hundred and fourteen patients aged between 18 and 52 years (age 27.8±13.2 years; 71 men and 43 women) were enrolled. After adding LTG, 105 patients (92.11%) completed adjunctive therapy. Upon completion of the adjunctive phase, mean improvement from baseline was 2.6 points on the LAEP (p=0.037). The overall score on the QOLIE-31 improved by 8.49 points from baseline (p=0.023). At the end of the trial, 26 (22.81%) of patients completed LTG monotherapy, and 65 patients (57.02%) experienced at least 50% reduction in seizure frequency compared to baseline, The mean improvement from baseline was 5.1 points on the LAEP (p=0.0059), and the overall score on the QOLIE-31 score improved by 12.72 points from baseline(p=0.0071). Twenty-two (19.30%) patients reported adverse effects and 9 patients discontinued participation in the trial because of adverse effects. Conclusion: For patients with partial seizures who were dissatisfied with their AED regimen because of intractable seizures, adding LTG to the drug regimen was well tolerated and effective in improving the quality of life and controlling seizures. Furthermore, switching to LTG monotherapy was associated with further improvement.     

Which patients become seizure free with antiepileptic drugs? An observational study in 821 patients with epilepsy

Objectives –  Analysis of factors influencing seizure outcome in antiepileptic drug treatment of epilepsy.
Patients and methods –  Retrospective analysis of 500 patients with complete seizure control and 321 patients with refractory epilepsy (mean ages 33.3 and 32.1 years respectively).
Results –  The seizure-free group consisted of 377 patients with symptomatic/cryptogenic epilepsy (SCE; mean seizure control 45 months) and 123 patients with idiopathic generalized epilepsy (IGE; mean seizure control 61 months) ( P  = 0.02). Of the patients with SCE, 35.7% had achieved seizure control with monotherapy (MT), 29.6% with ≥2 AEDs. No single AED was superior in MT. Of the patients with IGE, 35.9% had become seizure free with MT, 15.6% on combination therapy (CT). Valproate MT was more commonly associated with seizure freedom than lamotrigine ( P  < 0.05).
Conclusions –  The results indicate that, in SCE, seizures can be controlled with carefully selected CT more commonly than suggested by previous studies. The seizure prognosis of patients with IGE presenting to a specialist in epilepsy may be worse than previously thought.