新诊断成人癫痫患者托吡酯单药治疗疗效分析

目的研究托吡酯单药治疗成人各种类型癫痫的疗效。方法选择71例新诊断成人癫痫患者首选托吡酯治疗,回顾性分析其疗效及不良反应。结果发作完全控制33例(占46.5%),发作频率减少≥75%10例(占14.1%),发作频率减少≥50%14例(占19.7%),发作频率无减少14例(占19.7%);单纯部分性发作,复杂部分性发作,全面性发作总有效率分别为85.2%,72.7%,81.8%。结论托吡酯可用于成人各种类型癫痫发作的单药治疗,且耐受性好,不良反应少。     

Choosing a first drug treatment for epilepsy after SANAD: randomized controlled trials, systematic reviews, guidelines and treating patients

The ILAE treatment guidelines for initial monotherapy emphasise the poor quality of information available to inform everyday clinical practice. Industry sponsored studies comparing antiepileptic drugs answer restricted licensing questions, rather than those relevant to the clinical community (patients, health professionals and founders of health care). The SANAD study, a pragmatic randomized clinical trial, offers a methodology to address some of these questions. It identifies lamotrigine as a cost-effective alternative to carbamazepine for the treatment of focal epilepsies, but confirms valproate as the most effective drug for the treatment of generalized or unclassified epilepsy.     

Aggravation of seizures and/or EEG features in children treated with oxcarbazepine monotherapy

PURPOSE: Exacerbation of epilepsy may occur following initiation of therapy with antiepileptic drugs (AEDs). The aim of this study is to analyze the clinical and EEG characteristics of a group of pediatric patients with worsening of seizures and/or EEG deterioration while on oxcarbazepine (OXC). METHODS: A retrospective analysis of a clinical database was performed to identify patients with epilepsy treated with OXC over the past 3 years. History, neurological examination, and EEG findings were reviewed to identify any who had developed exacerbation of seizures or new abnormalities on EEG. RESULTS: Of 290 patients on OXC, we identified 12 patients with new onset seizures, all with initial normal neurological exam and normal EEG, who developed either worsening of preexisting seizures, new seizure types, and/or EEG deterioration following introduction of OXC monotherapy. EEG changes were primarily characterized by new onset of generalized epileptiform activity not reported on the initial baseline EEG. Following substitution of OXC with a broad spectrum AED, significant improvement of seizure control and improvement in the EEG was observed. CONCLUSIONS: These findings suggest that OXC can aggravate seizures and/or worsen EEG features in children. Following initiation of therapy with OXC, monitoring of patients with follow-up EEGs may be important, especially in patients who do not show adequate response to therapy.     

唑来膦酸单药治疗肺癌合并骨转移的临床研究

目的探讨唑来膦酸单药治疗肺癌合并骨转移的临床疗效。方法将56例肺癌合并骨转移的患者随机分为两组,分别使用唑来膦酸和帕米膦酸单药静脉滴注治疗,治疗3个月后,比较两组患者的疼痛治疗效果、生活质量评分(QOL)、一般状况评分(KPS)及不良反应的发生情况。结果两组的疼痛治疗有效率、不良反应的发生率比较,差异均无统计学意义(P>0.05)。两组患者治疗后的QOL和KPS评分与治疗前比较,差异有统计学意义(P<0.05),但两组之间QOL和KPS评分比较,差异无统计学意义(P<0.05)。结论唑来膦酸可有效缓解肺癌并骨转移患者的疼痛,综合疗效与帕米膦酸相当。     

Clinical efficacy of aniracetam, either as monotherapy or combined with cholinesterase inhibitors, in patients with cognitive impairment: a comparative open study

Introduction: Dementia constitutes an increasingly prevalent cognitive disorder with serious socioeconomic implications. Aims: In the present study, we aimed to evaluate the efficacy of aniracetam, either as monotherapy or combined with cholinesterase inhibitors (ChEIs), in terms of several neuropsychological parameters, in a considerable number of patients with dementia. Results: In our prospective, open‐label study, we enrolled a total of 276 patients (mean age 71 ± 8 years, 95 males) with cognitive disorders. Our study population comprised four groups: no treatment group (n = 75), aniracetam monotherapy group (n = 58), ChEIs monotherapy group (n = 68), and group of combined treatment (n = 68). Patients were examined with validated neuropsychological tests at baseline, 3, 6, and 12 months of treatment. In patients treated with aniracetam, all studied parameters were adequately maintained at 6 and 12 months, while emotional state was significantly improved at 3 months. In patients treated with ChEIs, we observed a significant cognitive deterioration at 12 months. The comparison between aniracetam and ChEIs in patients with relatively mild dementia (15 ≤ MMSE ≤ 25) revealed a significantly better cognitive performance with aniracetam at 6 months and improved functionality at 3 months. Comparing aniracetam monotherapy with combined treatment in the same population, aniracetam performed better in the cognitive scale at 6 months, and displayed a notable tendency for enhanced mood at 12 months and improved functionality at 6 months. Conclusions: Our findings indicate that aniracetam (a nootropic compound with glutamatergic activity and neuroprotective potential) is a promising option for patients with cognitive deficit of mild severity. It preserved all neuropsychological parameters for at least 12 months, and seemed to exert a favorable effect on emotional stability of demented patients.     

Conversion to High Dose Gabapentin Monotherapy in Patients with Medically Refractory Partial Epilepsy

Summary: Purpose: To evaluate the safety and efficacy of high dose gabapentin (GBP) monotherapy (3,0004,800 mg/ day) in patients with medically refractory partial epilepsy.
Methods: GBP monotherapy at daily doses up to 4,800 mg was attempted in patients participating in the open-label phase of a double-blind, dose-controlled, GBP monotherapy trial. For those who achieved monotherapy, the types and severity of adverse events were assessed and the average seizure frequency per 28 days while maintained on the highest daily GBP dose was compared to the seizure frequency during the baseline phase of the double blind trial. Correlation analysis between GBP serum level, total daily dose, and percentage of seizure change from baseline was performed.
Results: A total of 45 patients participated in the open-label phase of the trial and 23 (51%) were converted successfully to GBP monotherapy. In those patients, the average daily gabapentin dose was 3,900 mg and the mean length of follow-up was 252 days. Compared to baseline, there was a mean reduction of 54%, 43%, and 14% for simple partial, complex partial and secondarily generalized seizures respectively, while maintained on high-dose GBP monotherapy. A significant linear correlation between daily GBP dosage (2,4004,800 mg) and resultant mean serum levels was found (r = 0.51; p < 0.01). There was no significant correlation between seizure frequency and total daily GBP dose or with serum levels. High-dose GBP monotherapy was well tolerated; only one patient exited the trial because of adverse events. The most common adverse event was tiredness/sleepiness and was not dose-related.
Conclusions: GBP monotherapy is well tolerated in daily doses of up to 4,800 mg and is effective in a subgroup of patients with medically refractory partial epilepsy.     

A phase II/III trial of bitopertin monotherapy compared with placebo in patients with an acute exacerbation of schizophrenia – Results from the CandleLyte study

Bitopertin is a glycine reuptake inhibitor postulated to improve N-methyl-d-aspartate receptor hypofunction by increasing synaptic glycine concentrations. This randomised, double-blind, placebo- and active-controlled phase II/III trial evaluated the efficacy and safety of bitopertin monotherapy over 4 weeks in patients with acute exacerbation of schizophrenia. Of 301 patients randomised, 299 received placebo (n=80), bitopertin 10 mg (n=80) or 30 mg (n=77), or olanzapine 15 mg (n=62). The primary endpoint, change from baseline in mean Positive and Negative Syndrome Scale (PANSS) total score, showed non-statistically significant improvements with bitopertin 30 mg and olanzapine vs. placebo: bitopertin 10 mg (–11.7; standard error [SE], 1.89; p=0.945), bitopertin 30 mg (–15.3; SE, 1.87; p=0.211), olanzapine (–14.9; SE, 2.13; p=0.295) and placebo (–11.9; SE, 1.90). The PANSS positive subscale score, a secondary endpoint, also showed improvement with bitopertin 30 mg (p=0.030) whereas a trend was observed with olanzapine (p=0.072) vs. placebo. Although not statistically significant, bitopertin 30 mg and olanzapine reduced overall illness severity (Clinical Global Impression–Severity Scale; p=0.098 and p=0.126, respectively). More patients receiving bitopertin 30 mg (51.3%) or olanzapine (52.5%) than placebo (32.9%) were ready for hospital discharge at Week 4 (bitopertin, p=0.014; olanzapine, p=0.024). In summary, this study failed due to lack of statistical separation of either bitopertin or olanzapine (active control) from placebo on the primary endpoint. Of interest, improved positive symptoms and readiness for hospital discharge were associated with both bitopertin and olanzapine treatment. Bitopertin was safe and well tolerated in this study.     

Efficacy and safety of linagliptin monotherapy in Asian patients with inadequately controlled type 2 diabetes mellitus: A multinational, 24‐week,randomized, clinical trial

Aims/Introduction

Asian patients represent a large portion of the global population with type 2 diabetes mellitus, but are underrepresented in trials of glucose-lowering therapies. The present randomized, phase III, placebo-controlled, double-blind, 24-week study evaluated the dipeptidyl peptidase-4 inhibitor, linagliptin, as monotherapy in Asian patients with inadequately controlled type 2 diabetes mellitus.

Materials and Methods

Patients who were treatment naïve or had been treated with one oral antidiabetes drug were randomized to either linagliptin 5 mg daily or a placebo after washout. The primary end-point was a change from baseline in glycated hemoglobin after 24 weeks.

Results

A total of 300 Asian (87% Chinese) patients with type 2 diabetes mellitus were randomized to linagliptin or placebo at a 2:1 ratio. After 24 weeks of treatment, adjusted mean (standard error) glycated hemoglobin decreased by a placebo-corrected −0.50 ± 0.11 (P < 0.0001). In patients with baseline glycated hemoglobin ≥8.5%, the placebo-corrected decrease in glycated hemoglobin was −0.91 ± 0.20% (P < 0.0001). Adverse events occurred in 28.0 and 28.3% of linagliptin and placebo patients, respectively, but few were drug-related (3.0 and 2.0%, respectively). Hypoglycemia was reported by one linagliptin patient and no placebo patients. Treatment with linagliptin was weight neutral.

Conclusions

In Asian patients with inadequately controlled type 2 diabetes mellitus, linagliptin 5 mg as monotherapy was efficacious and well tolerated over 24 weeks.     

Efficacy of ziprasidone monotherapy in patients with anxious depression: A 12-week,randomized, double-blind,placebo-controlled,sequential-parallel comparison trial

Anxious depression, defined as major depressive disorder (MDD) accompanied by high levels of anxiety, seems to be difficult to treat with traditional antidepressant monotherapy. The purpose of this study was to assess the efficacy of ziprasidone monotherapy in patients with anxious depression versus non-anxious depression. One hundred and twenty outpatients were enrolled in a 12-week study that was divided into two 6-week periods according to the sequential parallel comparison design. Patients were randomized in a 2:3:3 multi-ratio to receive ziprasidone for 12 weeks, placebo for 6 weeks, followed by ziprasidone for 6 weeks, or placebo for 12 weeks. Efficacy was measured according to the 17-item Hamilton Depression Rating Scale (HRDS-17), Quick Inventory of Depressive Symptomatology Self-Rated (QIDS-SR). Anxious depression was defined as a score of ≥7 on the HDRS-17 anxiety/somatization subscale. In phase I and II, ziprasidone monotherapy led to no significant changes compared with placebo on the HDRS-17 and QIDS-SR scores in patients with both anxious and non-anxious depression. In the pooled analysis, ziprasidone monotherapy also produced no significance on the HDRS-17 (Z = 0.25, P = 0.80) and QIDS-SR (Z = 0.43, P = 0.67) in patients with anxious depression. In conclusion, treatment with ziprasidone monotherapy may produce no significant improvement compared with placebo in patients with in anxious depression.Trial registrationClinicalTrials.gov identifier: NCT00555997.