Pediatric status epilepticus: improved management with new drug therapies?

Introduction: Status Epilepticus (SE) is the most common neurological emergency of childhood. It requires prompt administration of appropriately selected anti-seizure medications.

Areas covered: Following a distinction between estabilished and emergent drugs, we present pharmacological treatment options and their clinical utility in children, with a short mention on alternatives to drug treatment. We also propose an algorithm for the management of pediatric SE. For this review a Pubmed, Medline and Embase search was performed.

Expert opinion: In early SE in children, in the prehospital setting, rectal diazepam or buccal midazolam are efficacious drugs; whereas in the hospital setting, intravenous lorazepam or diazepam are indicated. As regard estabilished stage of SE, in addition to the ‘classic’ compounds, such as phenytoin and phenobarbital, other drugs such as valproic acid, levetiracetam and lacosamide have been demonstrated efficacious. Treatment recommendations of refractory SE depend on retrospective case series and uncontrolled studies. We reported experiences about the use of midazolam, propofol, ketamine and lidocaine. They could be a valid option, but further prospective studies are necessary. Over the last few decades, important advances in basic mechanisms underlying refractory SE have been achieved, but few data are available regarding management of these stages.     

Therapeutic choices in convulsive status epilepticus

Introduction: Convulsive status epilepticus (SE) is one of the most frequent and severe neurological emergencies in both adults and children. A timely administration of appropriate antiepileptic drugs (AEDs) can stop seizures early and markedly improve outcome.

Areas covered: The main treatment strategies for SE are reviewed with an emphasis on initial treatments. The established first-line treatment consists of benzodiazepines, most frequently intravenous lorazepam. Benzodiazepines that do not require intravenous administration like intranasal midazolam or intramuscular midazolam are becoming more popular because of easier administration in the field. Other benzodiazepines may also be effective. After treatment with benzodiazepines, treatment with fosphenytoin and phenobarbital is usually recommended. Other intravenously available AEDs, such as valproate and levetiracetam, may be as effective and safe as fosphenytoin and phenobarbital, have a faster infusion time and better pharmacokinetic profile. The rationale behind the need for an early treatment of SE is discussed. The real-time delays of AED administration in clinical practice are described.

Expert opinion: There is limited evidence to support what the best initial benzodiazepine or the best non-benzodiazepine AED is. Recent and developing multicenter trials are evaluating the best treatment options and will likely modify the recommended treatment choices in SE in the near future. Additionally, more research is needed to understand how different treatment options modify prognosis in SE. Timely implementation of care protocols to minimize treatment delays is crucial.     

Refractory generalised convulsive status epilepticus : a guide to treatment

The patient with status epilepticus has continuous or rapidly repeating seizures. Generalised convulsive status epilepticus (GCSE) is the most common form of the disorder and is a life-threatening condition that requires prompt medical management. Status epilepticus that does not respond to first-line benzodiazepines (lorazepam or diazepam) or to second-line antiepileptic drugs (phenytoin/fosphenytoin, phenobarbital or valproate) is usually considered refractory and requires more aggressive treatment.The optimal treatment of refractory GCSE has not been defined, but patients should be treated in an intensive care unit, as artificial ventilation and haemodynamic support are required. Invasive haemodynamic monitoring is often necessary and EEG monitoring is essential.The drug treatment of refractory GCSE involves general anaesthesia with continuous intravenous anaesthetics given in doses that abolish all clinical and electrographic epileptic activity, often requiring sedation to the point of burst suppression on the EEG. Barbiturate anaesthetics, pentobarbital in the US and thiopental sodium in Europe and Australia, are the most frequently used agents and are highly effective for refractory GCSE both in children and adults. Indeed, they remain the only way to stop seizure activity with certainty in severely refractory cases. Other options are midazolam for adults and children and propofol for adults only.Regardless of the drug selected, intravenous fluids and vasopressors are usually required to treat hypotension. Once seizures have been controlled for 12-24 hours, continuous intravenous therapy should be gradually tapered off if the drug being administered is midazolam or propofol. Gradual tapering is probably not necessary with pentobarbital or thiopental sodium. Continuous EEG monitoring is required during high-dose treatment and while therapy is gradually withdrawn. During withdrawal of anaesthetic therapy, intravenous phenytoin/fosphenytoin or valproate should be continued (these agents having been administered during earlier phases of GCSE) to ensure an adequate baseline of antiepileptic medication so as to prevent the recurrence of status epilepticus. If additional medication is needed, the most appropriate antiepileptic drugs are gabapentin for focal seizures and levetiracetam and topiramate for all seizure types, as these drugs can be started at high doses with a low risk of idiosyncratic reactions.Even with current best practice, mortality in patients who experience refractory GCSE is about 50% and only the minority return to their premorbid functional baseline. Therefore, new treatment options are urgently needed. The ideal new drug for refractory GCSE would be one that has the ability to stop seizures more effectively and safely than current drugs, and that has neuroprotective properties to prevent the brain damage and neurological morbidity caused by GCSE.     

Anti-epileptic drugs associated with fractures in the elderly: a preliminary population-based study

Objective: Although classic anti-epileptic drugs have been associated with increased fracture risk, data are lacking on the outcomes of newer anti-epileptic drugs, such as gabapentin (GBP), levetiracetam, pregabalin, oxcarbazepine (OXC), and topiramate. This study was designed to determine fracture risks in the elderly associated with newly-developed anti-epileptic drugs.

Methods: A total of 2,169 patients (median age = 71.01 years, SD = 11.25 years) who experienced fractures between 2006 and 2013 were selected. For each case, age-, sex-, and comorbidity-matched controls were selected. The assessed clinical outcome was any fracture, and the use of anti-epileptic drugs was used as an exposure variable.

Results: There were no differences in age, sex, or comorbidities between patients and controls, but patients with fractures often lived in urban areas (odds ratio [OR]?=?1.17; 95% confidence interval [CI]?=?1.05–1.29) and had low income (OR = 1.14; 95% CI = 1.01–1.29) compared to controls. A significant increase in fractures was associated with OXC (OR = 3.31; 95% CI = 1.59–6.92), carbamazepine (CBZ; OR = 2.18; 95% CI = 1.31–3.61), and GBP (OR = 1.79; 95% CI = 1.01–3.18). Phenobarbital (OR = 1.97; 95%CI = 0.53–7.34), phenytoin (OR = 0.52; 95% CI = 0.23–1.16), levetiracetam (OR = 1.84; 95% CI = 0.55–6.16), valproic acid (OR = 1.01; 95% CI = 0.53–1.92), lamotrigine (OR = 1.44; 95% CI = 0.12–16.65), and topiramate (OR = 0.47; 95% CI = 0.10–2.31) were not associated with fracture risk.

Conclusions: CBZ, GBP, and OXC users have a significantly higher risk of fracture. Most recently-developed anti-epileptic drugs are not associated with an increased risk of fracture in individuals aged ≥50 years.     

SD大鼠神经干细胞评价药物神经毒性模型研究

目的：应用SD大鼠神经干细胞评价药物的神经毒性,为新药早期筛选和临床前安全性评价提供体外替代方法。方法：体外培养SD大鼠神经干细胞,传代后得到稳定的第二代神经球。以已知具有神经毒性的长春新碱、顺铂、瑞芬太尼、丙泊酚注射液、丙戊酸钠、苯妥英钠、丙烯酰胺、乙醇、氧化铁纳米粒子作为神经毒性阳性物质,以培养基作为神经毒性空白对照品;以没有神经毒性且具有促进神经细胞生长的神经生长因子作为检测模型的敏感性;以验证SD大鼠神经干细胞模型对神经毒性药物的检出能力。结果：长春新碱、顺铂、丙泊酚注射液、苯妥英钠、丙烯酰胺、氧化铁纳米粒子可引起全部或部分神经球解离破碎,神经干细胞坏死。顺铂、丙戊酸钠和苯妥英钠可见显著性的抑制神经球聚集。长春新碱、顺铂、瑞芬太尼、氧化铁纳米粒子、丙泊酚注射液、丙戊酸钠、苯妥英钠、丙烯酰胺、乙醇均表现剂量相关性的神经干细胞增殖毒性作用。神经生长因子可见促进神经球聚集及神经干细胞增殖。结论：本文以SD大鼠神经干细胞模型,以神经干细胞体外生长发育指标,验证了已知神经毒性抗肿瘤药物、麻醉剂、抗癫痫药物等的神经毒性特征。评价结果与这些药物已知的神经毒性作用特点一致,该评价方法可作为药物神经毒性临床前安全性评价研究的体外替代试验。     

Levetiracetam versus phenytoin for seizure prophylaxis in brain injured patients: a systematic review and meta-analysis

Background The onset of early and/or late seizures in brain injured patients is associated with worse outcome. So far, phenytoin is the most commonly used antiepileptic drug to prevent seizures in this group of patients. Objective In the current metaanalysis, we aimed to compare the efficacy and safety of phenytoin versus levetiracetam for seizure prophylaxis in brain injured patients. Methods A systematic search was conducted in PubMed and Cochrane Library Database by 2 investigators. Four randomized controlled trials (RCTs) were included (295 patients). Data were extracted and the quality of each RCT was assessed. Results Levetiracetam was found to be more effective than phenytoin in seizure prophylaxis (OR = 0.23; CI 95% [0.09–0.56]; Q test p value = 0.18 and I² = 38%). A trend toward less serious side effects was also found in patients treated with levetiracetam (OR = 0.27; CI 95% [0.07–1.07]; Q test p value = 0.72 and I² = 0%). Conclusion Levetiracetam is more effective and safer than phenytoin for seizure prophylaxis in brain injured patients.     

丙戊酸钠与苯妥英钠治疗癫痫持续状态的系统评价

目的系统评价丙戊酸钠与苯妥英钠治疗癫痫持续状态的疗效。方法计算机检索Medline、Embase、Pub Med图书馆、中文期刊全文数据库(CNKI)、万方数据库和维普等数据库(检索时限均从建库至2013年9月),收集国内外关于丙戊酸钠与苯妥英钠片治疗癫痫的随机对照实验。按照Cochrane系统评价的要求,制定纳入与排除标准,由3名研究者独立进行纳入研究的方法学质量评价和有效数据提取,采用Rev Man 5.2软件进行Meta分析。结果共纳入6个RCT,430例患者。Meta分析结果显示,丙戊酸钠组与苯妥英钠组在癫痫控制有效率方面效果类似[P=0.56>0.05,OR=1.14,95%CI=(0.73,1.76)];丙戊酸钠组与苯妥英钠组在治疗癫痫的复发率方面效果也类似[P=0.91>0.05,OR=0.97,95%CI=(0.54,1.72)]。结论当癫痫患者进行治疗时,可以考虑选用丙戊酸钠或苯妥英钠进行治疗。受纳入研究数量及质量限制,本系统评价结果尚需更多高质量、大样本、多中心随机对照实验验证。     

The problem of osteoporosis in epileptic patients taking antiepileptic drugs

Introduction: Epilepsy is a common neurological disorder associated with recurrent seizures. Therapy with antiepileptic drugs (AEDs) helps achieve seizure remission in approximately 70% of epileptic patients. Treatment with AEDs is frequently lifelong and there are reports suggesting its negative influence on bone health. This is especially important in terms of general occurrence of osteoporosis, affecting over 50 million people worldwide.

Areas covered: This study refers to two main groups of AEDs: hepatic enzyme inducers (carbamazepine, oxcarbazepine, phenobarbital, phenytoin, primidone and topiramate) and non-inducers (clobazam, clonazepam, ethosuximide, gabapentin, lacosamide, lamotrigine, levetiracetam, pregabalin, tiagabine, valproate, vigabatrin and zonisamide). Some reports indicate that enzyme inducers may exert a more negative influence on bone mineral density (BMD) compared to non-inducers. Bone problems may appear in both sexes during AED therapy, although women are additionally burdened with postmenopausal osteoporosis. Supplementation of vitamin D and calcium in patients on AEDs is recommended.

Expert opinion: Apart from enzyme inducers, valproate (an even enzyme inhibitor) may also negatively affect BMD. However, the untoward effects of AEDs may depend upon their doses and duration of treatment. Although the problem of supplementation of vitamin D and calcium in epileptic patients on AEDs is controversial, there are recommendations to do so.     

丙戊酸钠、奥卡西平与左乙拉西坦分别治疗小儿癫痫的疗效及对认知功能的影响

目的 探讨丙戊酸钠、奥卡西平与左乙拉西坦分别治疗小儿癫痫的疗效及对小儿认知功能的影响。方法 收取2011年4月—2016年1月于渭南市妇幼保健院进行治疗的癫痫患儿96例作为研究对象,根据随机数字表法将其分为A、B、C组,每组各32例,分别使用丙戊酸钠、奥卡西平或左乙拉西坦进行治疗,3组患儿均治疗16周。对3组患儿临床疗效、脑电变化情况、认知功能变化情况以及用药安全性进行观察与比较。结果 A、B、C组治疗总有效率分别为71.88%、78.13%、90.63%,C组高于A、B组,但三组间比较无统计学差异。随治疗时间延长,3组患儿痫样放电好转率逐渐升高。C组好转率高于B组更高于A组,组间比较差异均有统计学意义（P＜0.05）。3组患儿治疗前语言智商（VIQ）、操作智商（PIQ）及总智商（FIQ）均无显著差异,治疗后B、C两组均较治疗前得分显著升高,且高于同期A组得分,差异有统计学意义（P＜0.05）。A组不良反应发生率为28.13%,B组为12.50%,C组为3.13%,3组间比较差异显著（P＜0.05）。结论 丙戊酸钠、奥卡西平与左乙拉西坦单药治疗小儿癫痫疗效相当,但奥卡西平与左乙拉西坦对脑电功能及小儿认知功能改善具有更加积极的意义,且以左乙拉西坦的安全性更高,具有更好的应用价值。     

Testing of prototype antiepileptics in hippocampal slices

Summary The effects of six prototype anticonvulsant drugs, phenytoin, carbamazepine, midazolam, phenobarbital, ethosuximide and sodium valproate, were evaluated in two different experimental models of epileptiform activity using the in vitro slice preparation from the rat hippocampus. The relative potencies of the agents were determined: a) in the complete absence of synaptic transmission by recording spontaneous burst firing from the CA 1 pyramidal cell layer in a low calcium high magnesium solution and b) during blocked synaptic inhibition by observing the activity of each drug upon orthodromically evoked population spikes in penicillin containing medium. The rank order of potencies was a) in low Ca²⁺: carbamazepine, phenytoin, midazolam, phenobarbital, valproate, ethosuximide; b) in penicillin containing medium: midazolam, phenobarbital, carbamazepine, phenytoin, valproate, ethosuximide. These observations illustrate that the use of multiple paradigms is warranted when examining the mechanisms of action of new anticonvulsants.     

2015—2017年解放军总医院抗癫痫药物的使用情况分析

目的 了解解放军总医院抗癫痫药物的应用情况与趋势。方法 采用世界卫生组织（WHO）推荐的以限定日剂量（DDD）为指标的分析方法,对2015-2017年解放军总医院抗癫痫药物的用药金额、用药频度（DDDs）、日均费用（DDC））和排序比（B/A）等进行统计分析。结果 左乙拉西坦、奥卡西平和丙戊酸钠的用药金额始终处于前3位,加巴喷丁的用药金额逐渐上升,托吡酯的用药金额逐渐下降;用药频度（DDDs）排序列前3位的是左乙拉西坦、奥卡西平和丙戊酸钠,左乙拉西坦的DDDs逐年上升,2017年已跃居至第1位;2015-2016年各种抗癫痫药物的DDC较为稳定,2016-2017年各种抗癫痫药物的DDC开始略有下降;除拉莫三嗪的排序比值始终小于1.00,其他抗癫痫药物的B/A均在1.00以上波动。结论 解放军总医院抗癫痫治疗以新型抗癫痫药物为主,其中左乙拉西坦和奥卡西平具有很好的市场前景。     

Use of Newer Anticonvulsants for the Treatment of Status Epilepticus

Status epilepticus (SE) has a high mortality rate and is one of the most common neurologic emergencies. Fast progression of this neurologic emergency and lack of response to traditional antiepileptic drugs (AEDs) in most cases has challenged clinicians to use new agents. This article evaluates the efficacy and safety of AEDs released to the market after 2000 for SE, refractory status epilepticus (RSE), and super-refractory status epilepticus (SRSE). The PubMed database was searched for clinical trials published between January 2000 and July 2018 using the search terms status epilepticus, refractory status epilepticus, super refractory status epilepticus, brivaracetam, clobazam, cannabidiol, eslicarbazepine, lacosamide, perampanel, rufinamide, stiripentol, and zonisamide. Trials that evaluated these agents in adults with SE, RSE, and SRSE were included. Brivaracetam use was identified in two retrospective reviews with success rates of 27% and 57%. One unsuccessful case report of cannabidiol use in SE was found. Four clobazam studies were identified in SE and RSE with success rates ranging from 25–100%. No evidence for the use of eslicarbazepine and zonisamide was found. Using the search terms for lacosamide identified 38 articles: 1 systematic review, 5 prospective studies, 15 retrospective reviews, and 17 case reports. Success rates and dosing varied, but studies that included focal or partial types of SE showed higher success rates. Five articles were identified regarding perampanel use in this setting. Three were retrospective reviews with success rates ranging from 17–60%, and two were case reports. Only one case report regarding the use of rufinamide was found; rufinamide titrated up to 4.4 mg/day allowed discontinuation of barbiturate and clobazam. One case report and two case series of stiripentol were found with reported efficacy between 60% and 100% in SRSE. Evidence is currently insufficient to support the use of these agents in this setting.     

Comparative efficacy and tolerability of anti-epileptic drugs for refractory focal epilepsy: systematic review and network meta-analysis reveals the need for long term comparator trials

Aims

To evaluate the comparative efficacy (50% reduction in seizure frequency) and tolerability (premature withdrawal due to adverse events) of anti-epileptic drugs (AEDs) for refractory epilepsy.

Methods

We searched Cochrane Central Register of Controlled Trials (Cochrane Library 2009, issue 2) including Epilepsy Group''s specialized register, MEDLINE (1950 to March 2009), EMBASE (1980 to March 2009), and Current Contents Connect (1998 to March 2009) to conduct a systematic review of published studies, developed a treatment network and undertook a network meta-analysis.

Results

Forty-three eligible trials with 6346 patients and 12 interventions, including placebo, contributed to the analysis. Only three direct drug comparator trials were identified, the remaining 40 trials being placebo-controlled. Conventional random-effects meta-analysis indicated all drugs were superior in efficacy to placebo (overall odds ratio (OR] 3.78, 95% CI 3.14, 4.55) but did not permit firm distinction between drugs on the basis of the efficacy or tolerability. A Bayesian network meta-analysis prioritized oxcarbazepine, topiramate and pregabalin on the basis of short term efficacy. However, sodium valproate, levetiracetam, gabapentin and vigabatrin were prioritized on the basis of short-term efficacy and tolerability, with the caveat that vigabatrin is recognized as being associated with serious visual disturbance with chronic use.

Conclusion

Of the wide range of AEDs licensed for the treatment of refractory epilepsy, sodium valproate, levetiracetam and gabapentin demonstrated the best balance of efficacy and tolerability. Until regulators mandate greater use of active comparator trials with longer term follow-up, network meta-analysis provides the only available means to quantify these clinically important parameters.     

A viewpoint on rational and irrational fixed-drug combinations

Introduction: Considering that there are around 30% of patients with epilepsy resistant to monotherapy, the use of synergistic combinations of antiepileptic drugs is of particular importance. This review shows most beneficial as well as irrational combined treatments both from an experimental and clinical point of view.

Areas covered: Preferably, experimental data derived from studies evaluating synergy, additivity, or antagonism by relevant methods, in terms of anticonvulsant or neurotoxic effects and pharmacokinetic data have been considered. Although there have been no randomized clinical trials on this issue, the clinical data have been analyzed from studies on considerable numbers of patients. Case-report studies have been not considered.

Expert commentary: The experimental data provide a strong support that co-administration of lamotrigine with carbamazepine is negative, considering the anticonvulsant and neurotoxic effects. Clinical reports do not entirely support this conclusion. Other experimentally documented negative combinations comprise lamotrigine+ oxcarbazepine and oxcarbazepine+ phenytoin. From the experimental and clinical point of view, a combination of lamotrigine+ valproate may deserve recommendation. Other most positive experimental and clinical combinations include carbamazepine+valproate, phenytoin+phenobarbital, carbamazepine+gabapentin, carbamazepine+topiramate, levetiracetam+valproate, levetiracetam+carbamazepine. Certainly, experimental data have some limitations (non-epileptic animals, acute administration of antiepileptic drugs) so all experimental recommendations need a careful clinical evaluation.     

Efficacy and safety analysis of new P2Y12 inhibitors versus clopidogrel in patients with percutaneous coronary intervention: a meta-analysis

Objective:

New P2Y₁₂ inhibitors, classified as oral (prasugrel and ticagrelor) and intravenous (cangrelor and elinogrel) drugs, have shown improved antithrombotic effects compared with clopidogrel in patients with acute coronary syndrome (ACS) or patients undergoing percutaneous coronary intervention (PCI) in landmark trials. The purpose of this study was to perform a meta-analysis of randomized trials that compared new P2Y₁₂ inhibitors with clopidogrel to determine their efficacy and safety in patients undergoing PCI.

Methods:

Randomized controlled trials of at least 4 weeks, comparing new P2Y₁₂ inhibitors with clopidogrel in PCI, were identified using the electronic databases Cochrane Central Register of Controlled Trials, Medline, PubMed, Web of Science, and Google Scholar from January 1, 1980, to July 31, 2014.

Main outcome measures:

The primary efficacy endpoints were all-cause death and major adverse cardiovascular events (MACEs). The primary safety endpoint was thrombolysis in myocardial infarction (TIMI) major bleeding.

Results:

Twelve studies including 71,097 patients met the inclusion criteria. New P2Y₁₂ inhibitors significantly reduced all-cause death (odds ratio [OR]: 0.81; 95% confidence interval [CI] 0.73–0.90, p?p?p?p?=?0.03) and cardiovascular death (OR 0.82; 95% CI 0.73–0.92, p?=?0.001) compared with clopidogrel. There were no significant differences between stroke (OR 0.87; 95% CI 0.72–1.05, p?=?0.14) and major bleeding events (OR 1.22; 95% CI 0.99–1.52, p?=?0.06) between the new P2Y₁₂ inhibitor and clopidogrel groups.

Conclusion:

New P2Y₁₂ inhibitors decreased death in patients undergoing PCI compared with clopidogrel with a considerable safety and tolerability profile; however, the risk/benefit ratio of ischemic and bleeding events should be further investigated.     

奥氮平联合丙戊酸钠治疗难治性癫痫持续状态的临床效果观察

目的 观察奥氮平联合丙戊酸钠治疗难治性癫痫持续状态的临床效果。方法 采用回顾性、随机对照研究方法,将2015年2月—2017年9月在遂宁市中心医院诊治的难治性癫痫持续状态患者190例分为观察组与对照组各95例,对照组给予丙戊酸钠治疗,初剂量为5~10 mg/（kg·d）,然后每周增加剂量5~10 mg/（kg·d）,持续增加到剂量为20~30 mg/（kg·d）后进行维持治疗。观察组在对照组治疗的基础上给予奥氮平6 mg治疗,1次/d。两组都治疗观察4周。比较两组近期疗效、不良反应及认知功能情况。结果 观察组与对照组的总有效率分别为98.9%和88.4%,观察组明显高于对照组,差异有统计学意义（P<0.05）。观察组的不良反应发生率4.2%与对照组（6.3%）无统计学差异。两组治疗后的简易精神状态检查量表（MMSE）评分均明显高于治疗前,同组治疗前后比较差异有统计学意义（P<0.05）;且观察组的MMSE评分明显高于对照组,组间差异有统计学意义（P<0.05）。结论 奥氮平联合丙戊酸钠治疗难治性癫痫持续状态能提高治疗效果,不会增加不良反应的发生,能促进患者认知功能的改善,有很好的应用效果。     

Uric acid and incident chronic kidney disease in dyslipidemic individuals

Background: Elevated uric acid (UA) is a recognized risk factor for chronic kidney disease (CKD). This study aimed to investigate whether this association exists in dyslipidemic patients receiving multifactorial treatment.

Methods: An observational study conducted in Greece including 1,269 dyslipidemic individuals followed-up in a lipid clinic for ≥3 years. Estimated glomerular filtration rate (eGFR) was calculated by CKD-EPI equation and CKD was defined as ≤60?mL/min/1.73 m². The correlation was assessed between UA levels and the CKD risk after adjusting for potential confounding factors, after defining the following UA quartiles: Q1: ?6?mg/dL.

Results: After excluding patients with baseline eGFR <60?mL/min/1.73 m², gout and those taking UA-lowering drugs, 1,095 individuals were eligible; of those, 91% and 69% were treated with statins and anti-hypertensive drugs, respectively. During their follow-up (6 years; IQR?=?4–10), 11.9% of the subjects developed CKD, whereas the median annual eGFR decline was 0.69?mL/min/1.73 m² (IQR?=?0.45–2.33). Multivariate analysis showed that baseline UA levels (HR?=?1.26; 95% CI?=?1.09–1.45, p?=?.001), female gender (HR?=?1.74; 95% CI?=?1.14–2.65, p?=?.01), age (HR?=?1.10; 95% CI?=?1.07–1.12, p?p?=?.03), cardiovascular disease (HR?=?1.62; 95% CI?=?1.02–2.58, p?=?.04), decreased baseline renal function (eGFR <90?mL/min/1.73 m²) (HR?=?2.38; 95% CI?=?1.14–4.81, p?=?.02), and low-density lipoprotein cholesterol reduction (HR?=?0.995; 95% CI?=?0.991–0.998, p?=?.01) were associated with incident CKD. Additionally, patients with UA ≥6?mg/dL exhibited a higher risk of incident CKD compared with those in the lowest UA quartile (HR?=?2.01; 95% CI?=?1.11–3.65, p?=?.02).

Conclusion: Higher UA levels are correlated with a higher risk of incident CKD in dyslipidemic individuals taking multifactorial treatment.     

Treating myoclonic epilepsy in children: state-of-the-art

Introduction: Myoclonic seizures can be observed in various clinical settings and different epileptic conditions, including some forms of both diopathic and symptomatic epilepsies. Relatively little has been written on treatment of myoclonic seizures. Some old antiepileptic drugs, such as valproate and some benzodiazepines, are widely used but more treatment options exist today for some newer antiepileptic drugs. Nevertheless, patients can be refractory to drug treatment and some drugs may exacerbate or even induce myoclonus.

Areas covered: Key safety, tolerability, and efficacy data are presented for different antiepileptic drugs with antimyoclonic effect, alone and/or in combination.

Expert opinion: Treatment of myoclonic seizures in children is mainly based on prospective and retrospective studies, with little evidence from randomized clinical trials. Valproate is commonly the first choice alone or in combination with some benzodiazepines or levetiracetam. There is still insufficient evidence for the use of topiramate and zonisamide as monotherapy. Of major importance remains avoidance of medication that may aggravate the seizures. Better understanding of pathophysiologic mechanisms of myoclonic seizures and myoclonic epilepsies could yield great improvement in the treatment and quality of life of patients.     

2012-2014年南京地区34家医院抗癫痫药物利用分析

目的: 评价南京地区医院抗癫痫药的应用现状及趋势。方法: 对南京地区34家医院2012-2014年抗癫痫药的品种、用量、销售金额、用药频度等进行回顾性统计、分析。结果: 南京地区抗癫痫药销售金额逐年增加。各年度新型抗癫痫药销售金额均占抗癫痫药总销售金额的六成左右,DDDs所占比例从2012年的35.43%增长至2014年的45.53%。金额排序中丙戊酸钠各年度一直占据36%左右,稳居第一;新型抗癫痫药加巴喷丁、左乙拉西坦、奥卡西平销售金额逐年大幅增加,苯妥英钠、托吡酯年销售金额略有起伏。DDDs排序中丙戊酸钠以绝对优势稳居第一;新型抗癫痫药除托吡酯外用药频度均呈逐年增加趋势,而传统AEDs除丙戊酸钠外均逐年降低。结论: 南京地区抗癫痫药丙戊酸钠、奥卡西平选用倾向大,传统抗癫痫药丙戊酸钠在抗癫痫药中仍占据重要地位,新型抗癫痫药如奥卡西平、左乙拉西坦、拉莫三嗪、加巴喷丁等不良反应、耐受性、对肝药酶的影响性等优于传统抗癫痫药,市场前景良好。