Sodium valproate in migraine without aura and medication overuse headache: A randomized controlled trial

ObjectiveTo assess the efficacy, safety and tolerability of sodium valproate (800 mg/die) compared with placebo in medication-overuse headache patients with a history of migraine without aura.MethodsThis is a multicenter, randomized, double-blind, placebo-controlled study enrolled medication-overuse headache patients for a 3-month treatment period with sodium valproate (800 mg/day) or placebo after a 6 day outpatient detoxification regimen, followed by a 3-month follow-up. Primary outcome was defined by the proportion of patients achieving ≥50% reduction in the number of days with headache per month (responders) from the baseline to the last 4 weeks of the 3-month treatment. Multivariate logistic regression models were used on the primary endpoint, adjusting for age, sex, disease duration, comorbidity and surgery. The last-observation-carried-forward method was used to adjust for missing values.ResultsNine sites enrolled 130 patients and, after a 6-day detoxification phase, randomized 88 eligible patients. The 3-month responder rate was higher in the sodium valproate (45.0%) than in the placebo arm (23.8%) with an absolute difference of about 20% (p=0.0431). Sodium valproate had safety and tolerability profiles comparable to placebo.ConclusionsThe present study supports the efficacy and safety of sodium valproate in the treatment of medication overuse headache with history of migraine after detoxification.     

Effect of antidepressant medication resistance on short-term response to electroconvulsive therapy

This prospective study assessed the influence of resistance to antidepressant pharmacotherapy on the short-term response to subsequent electroconvulsive therapy (ECT). Previous research has shown that patients with medication resistance were less likely to respond to ECT. This finding may be applicable to the population of depressed inpatients in The Netherlands, where ECT is often preceded by several medication trials. Eighty-five patients (61 female and 24 male patients) with DSM-IV criteria for depressive disorder, both with and without mood congruent psychotic features, were included for analysis. Medication resistance was rated with the Antidepressant Treatment History Form. Medication resistance was predefined in accordance with the previous research in this field. When a reduction of at least 50% on the 17-item version of the Hamilton Rating Scale for Depression (HRSD) between pre- and post-ECT is used as response criterion, medication-resistant patients were equally likely to respond to subsequent ECT (30/48 = 82.5%) than patients without medication resistance (30/37 = 81.1%). Even when post-ECT HRSD score < or = 7 was used (full remission), there was no significant difference between medication-resistant patients (21/48 = 43.8%) and patients without medication resistance (15/37 = 40.5%). When potential confounding variables were taken into account, these differences remain nonsignificant. In contrast to earlier research, medication resistance does not influence short-term response to subsequent ECT and it can still be of considerable efficacy.     

PCI术后患者用药依从情况及影响因素分析

目的:了解PCI术后患者用药依从性的影响因素。方法:对501例PCI术后患者进行问卷调查。结果:501例患者中,服药依从性佳者440例,占87.8%,依从性差者61例,占12.2%。职业、支架植入时间、民族、方便获取药物及家人关心程度是影响患者用药依从性的因素。结论:PCI术后患者用药依从性高,可根据主要影响因素制定干预措施进一步提高患者的用药依从性。     

The impact of drug therapy on quality of life in headache and migraine

Although headache is among the most common and costly disorders in primary care, our understanding of its direct impact on the quality of life of affected individuals is incomplete. While studies evaluating the role of headache on health-related quality of life and healthcare economics are starting to appear in the medical literature, the effect of pharmacotherapy in improving quality of life is only beginning to be studied. At present, studies evaluating health-related quality of life in patients with migraine who are undergoing treatment are limited to 3 agents: sumatriptan, flurbiprofen and diclofenac. Several studies have consistently indicated that these drugs benefit patients by improving key dimensions of health-related quality of life or patients' sense of well-being to a significant extent. Given the magnitude of functional and emotional impairment associated with chronic headache disorders, assessing patients' perceptions of their quality of life makes a useful contribution to the evaluation of therapeutic interventions and should supplement traditional clinical endpoints in determining the effectiveness of new drugs.     

Frequency of common MDR1 gene variants in a Polish population

P-glycoprotein (P-gp) is a transmembrane transporter playing an important role in drug efflux. There is growing evidence that P-gp activity may be related to haplotypes of MDR1 gene. In the current study, the frequencies of common functional polymorphisms in MDR1 gene (2677G > A,T and 3435C > T) were evaluated using PCR-RFLP and allele-specific amplification, in a group of 204 healthy individuals of Caucasian origin from Poland. It was found that the frequencies of the studied single nucleotide polymorphisms were similar to those reported for other Caucasian populations, and were as follows: 2677G-3435C--0.453, 2677G-3435T--0.143, 2677T-3435C--0.015, 2677T-3435T--0.370, 2677A-3435C--0.008, 2677A-3435T--0.011. The results of our study may give the basis for predicting pharmacokinetic and pharmacodynamic effects of many commonly used drugs in the Polish population.     

The effect of clonidine on the naltrexone-induced withdrawal response in morphine-treated guinea-pigs

Rapid opioid withdrawal induced by naltrexone is now used as a treatment for heroin addiction. The alpha2-adrenoceptor agonist, clonidine, is currently used in clinical practice to reduce opioid withdrawal in humans. However, few studies have been reported on its effectiveness for this purpose. Guinea-pigs were made dependent and tolerant to morphine using a 3-day chronic morphine regimen (total 410 mg kg(-1) morphine base), and injected with either clonidine (0.1 mg kg(-1), s.c.) or saline, 1 h before induction of withdrawal with naltrexone (15 mg kg(-1), s.c.). Withdrawal behaviours were measured for 90 min and animals were then euthanased and the brains removed. The presence of the immediate early gene protein product, c-Fos, was detected using immunohistochemical techniques. Clonidine reduced the number of head/body shakes, but had no effect on the total withdrawal behaviour score. In the CNS, clonidine increased the number of Fos-LI neurons in the central amygdala. In conclusion, the modest effect of clonidine in the present experiments suggests that the efficacy of clonidine in humans undergoing naltrexone-induced opioid withdrawal requires further investigation.     

Polymorphic variants of the multidrug resistance gene Mdr1a and response to antiepileptic drug treatment in the kindling model of epilepsy

Allelic variants of the human P-glycoprotein encoding gene MDR1 (ABCB1) are discussed to be associated with different clinical conditions including pharmacoresistance of epilepsy. However, conflicting data have been reported with regard to the functional relevance of MDR1 allelic variants for the response to antiepileptic drugs. To our knowledge, it is not known whether functionally relevant genetic polymorphisms also occur in the two genes (Mdr1a/Abcb1a, Mdr1b/Abcb1b) coding for P-glycoprotein in the brain of rodents. Therefore, we have started to search for polymorphisms in the Mdr1a gene, which governs the expression of P-glycoprotein in brain capillary endothelial cells in rats. In the kindling model of temporal lobe epilepsy, subgroups of phenytoin-sensitive and phenytoin-resistant rats were selected in repeated drug trials. Sequencing of the Mdr1a gene coding sequence in the subgroups revealed no general differences between drug-resistant and drug-sensitive rats of the Wistar outbred strain. A comparison between different inbred and outbred rat strains also gave no evidence for polymorphisms in the Mdr1a coding sequence. However, in exon-flanking intron sequences, four genetic variants were identified by comparison between these rats strains.

In conclusion, the finding that Wistar rats vary in their response to phenytoin, while having the same genetic background, argues against a major impact of Mdr1a genetics on pharmacosensitivity to antiepileptic drugs in the amygdala kindling model.     

撤市药物的遗传药理学

药物安全性、药动学和药效学是决定候选化合物能否成药的重要指标,而上市后的药物遭遇撤市则多因发生严重的药物不良反应所致.药物在不同个体/人群中可能产生不同的药动学和药效学效应,甚至表现为不良反应,遗传药理学重在研究机体遗传因素对二者的影响.阐明遗传变异导致的药物药理作用异常的机制,不仅能加强药物使用的安全性,更全面地描述药物的适应范围,也可能改写药物被淘汰的命运,使之更好地服务于人类.     

中医定向透药疗法联合针刺治疗偏瘫后肩手综合征的疗效观察

目的 观察中医定向透药疗法联合针刺与单纯针刺治疗偏瘫后肩手综合征Ⅰ期的疗效观察.方法 将40例患者随机分为中医定向透药疗法联合针刺（20例）、单纯针刺治疗（20例）.采用Fugl-Meyer量表评价患肢运动功能;采用ADL量表评定日常生活活动能力;采用目测类比评分（VAS）评价疼痛及观察治疗前后肿胀程度.结果 上肢Fugl-Meyer运动功能和日常生活活动能力ADL评分,两组治疗前和治疗2个疗程后比较,差异有统计学意义（均P＜0.05）,两组间比较,中医定向透药疗法联合针刺组优于单纯针刺治疗组（P＜0.05）;两组治疗前后肿胀和疼痛评分都有下降（均P＜0.05）,组间比较,疼痛、肿胀程度改善中医定向透药疗法联合针刺组优于单纯针刺治疗组（P＜0.05）.观察中医定向透药疗法联合针刺组总有效率为95％,单纯针刺组为70％,两组疗效比较,差异具有统计学意义（P＜0.05）.结论 中医定向透药疗法联合针刺治疗偏瘫后肩手综合征在减轻肿胀、疼痛、改善运动功能及提高ADL生活能力方面优于单纯针刺治疗.     

The impact of medication resistance and continuation pharmacotherapy on relapse following response to electroconvulsive therapy in major depression

After clinical response to electroconvulsive therapy (ECT), 58 patients with major depressive disorder were followed for 1 year or until relapse. The rate of relapse was substantially higher in patients who had failed adequate antidepressant medication trials prior to ECT than in patients not determined to be medication resistant. Adequacy of post-ECT pharmacotherapy was only marginally related to likelihood of relapse. The subgroup of patients who appeared to benefit from adequate post-ECT pharmacotherapy were those who did not receive an adequate medication trial prior to ECT. The findings call into question the common practice of administering as continuation pharmacotherapy following ECT the same class of medications that patients had failed with during the acute episode prior to ECT. The findings also indicate that resistance to antidepressant medication is a strong predictor of relapse following response to ECT.     

住院式服药管理模式对戒毒人员高血压治疗效果的研究

目的:通过观察住院式服药管理对戒毒人员高血压治疗,从而了解其有效性、安全性、可操作性、经济性,为监管场所慢性病服药有效管理提供参考。方法:选取江苏省某强制隔离戒毒所医院2016年6月至2017年6月新收治的106名高血压患者为研究对象,按患高血压戒毒人员所在戒治大队分为对照组和观察组,对照组为甲乙大队46例高血压患者,实行常规门诊式服药管理;观察组为丙丁大队60例高血压患者,实行住院式服药管理。比较两组高血压戒毒人员服用降压药后疗效、不良事件发生情况、民警服药管理时间和人均治疗经费情况。结果:与对照组相比,观察组经过1个月、半年、一年服用降压药,血压控制程度好于对照组(P<0.05);1年来两组不良事件发生比较,观察组小于对照组(P<0.05);基层民警服药管理时间比较,观察组小于对照组(P<0.05);1年来两组人均治疗费用支出比较,观察组小于对照组(P<0.05);以上均具有可比性。结论:住院式服药管理不仅有利于戒毒人员慢性病病情的控制、降低不良事件发生,而且可节约医疗成本,具有可操作性,值得监管场所推广。     

从医院信息系统入手改变退药模式减少病区退药

目的： 通过优化信息系统，减少某医院病区实物退药，从而降低员工工作负荷，节省退药耗时。方法： 对现有医院信息管理系统进行改进，在原系统基础上介入冲减、退药模块，将病区需退的药品先通过系统冲减，未冲减的药品再进行实物退药，并计算改进前后退药耗时。结果： 医院信息系统改进后，3-5月的药品品种数分别冲减了（1 449/1 996）72.60%、（1 531/2 115）72.39%、（1 535/2 143）71.12%，同时，药品数量分别冲减了（11 194/15 111）74.08%、（11 579/16 282）71.12%、（11 700/16 001）73.12%。1月分别与3月、4月、5月相比，耗时从48.25 h分别下降到4.90，5.88，5.38 h，分别节约43.35，42.37，42.87 h。结论： 医院信息管理系统的改进有效地减少了病区的实物退药，为工作人员节省退药耗时的同时也保障了患者用药安全。     

Combined effect of drug and drive on the consolidation process

Rats of the Maudsley strains were trained in the Hebb-William's maze under three levels of food deprivation, i.e. 22, 25, and 7 h (drives) for 10 consecutive days. Immediately after each daily trial the experimental animals of all three drives were injected with a 1.0 mg/kg dose of picrotoxin, and the animals of the control groups were administered distilled water. Picrotoxin increased the efficiency of learning at all levels of drive, and higher drive level resulted in greater performance. The Reactive strain performed better in the maze learning than the Non-Reactive.This work was carried out at the Institute of Psychiatry, London S.E. 5.     

The impact of ergotamine-induced headache and ergotamine withdrawal on information processing

Ergotamine abuse and subsequent ergotamine-induced headache is a common problem in the pharmacological treatment of migraine and other headache types; often, withdrawal therapy is necessary. This study investigated whether ergotamine abuse affects information processing and whether withdrawal therapy can lead to an improvement of information processing. We designed a standardized neurophysiological retrospective (ergotamine abuse) and prospective (ergotamine withdrawal) study in a supraregional headache outpatient clinic. Seventy-one patients abusing ergotamine derivatives with subsequent daily headache were enrolled and compared to 36 migraine patients without ergotamine intake and 36 healthy subjects. Information processing was evaluated by latencies and amplitudes of visually evoked event-related potentials (ERP) before and after ergotamine withdrawal therapy. P3 latency of the ERP was significantly increased in ergotamine abuse (442 ± 45 ms) versus migraine (415 ± 40 ms) and healthy subjects (410 ± 33 ms), there was no difference between ergotamine tartrate and dihydroergotamine abuse. The migraine specific loss of habituation in information processing as measured by P3 latency could not be observed in migraine patients with ergotamine abuse. After successful withdrawal therapy in 36 patients, the abnormally prolonged P3 latency was significantly shortened (452 ± 47 ms versus 433 ± 30 ms; P < 0.004). Our findings imply that information processing is impaired by ergotamine abuse and can be improved but not normalized after withdrawal therapy. Furthermore, our data provide strong evidence that ergotamine, besides its peripheral effects, has a central mode of action. Received: 16 March 1998/Final version: 27 July 1998     

肥胖儿童哮喘临床特征及其对药物治疗反应性的研究

目的探讨肥胖儿童哮喘临床特征及其对药物治疗的反应性。方法选取2019年2月～2020年12月收治的儿童哮喘病例200例,进行回顾性分析。根据患儿体重指数(BMI)将其分为观察组与对照组。BMI≥28 kg/m²的100例患儿纳入观察组,BMI <28 kg/m²的100例患儿纳入对照组。两组患者均根据权威指南接受规范化吸入法治疗。对比两组患儿的临床特征以及治疗后的临床效果。结果对照组综合疗效总有效率为96.00%,观察组综合疗效总有效率为78.00%,两组相比,对照组综合疗效总有效率更高(P <0.05)。此外,两组患儿均未发生明显不良反应。治疗后,对照组患儿的IL-6和TNF-α水平均低于观察组患儿(P <0.05)。结论肥胖哮喘患儿的肺功能损害程度要大于正常体重的哮喘儿童。且在标准化治疗方案实施后,肥胖哮喘患儿的血清细胞因子指标不及正常体重哮喘患儿,这导致肥胖哮喘患儿的预后相对更差。临床上对于体重过大的哮喘患儿应足够重视,可考虑早期给予加强治疗,以改善患儿预后。     

Using the costs of drug therapy to screen patients for a community pharmacy-based medication review program

OBJECTIVES: To measure the positive predictive value (PPV) of the cost of drug therapy (threshold = 2000 Swiss francs [CHF], US$1440, 1360) as a screening criterion for identifying patients who may benefit from medication review (MR). To describe identified drug-related problems (DRPs) and expense problems (EPs), and to estimate potential savings if all recommendations were accepted. SETTING: Five voluntary Swiss community pharmacies. METHODS: Of 12,680 patients, 592 (4.7%) had drug therapy costs exceeding 2000 CHF over a six-month period from July 1 to December 31, 2002. This threshold limit was set to identify high-risk patients for DRPs and EPs. Three pharmacists consecutively conducted a medication review based on the pharmaceutical charts of 125 sampled patients who met the inclusion criterion. MAIN OUTCOME MEASURE: The PPV of a threshold of 2000 CHF for identifying patients who might benefit from a MR: true positives were patients with at least one DRP, while false positives were patients with no DRP. RESULTS: The selection based on this criterion had a PPV of 86% for detecting patients with at least one DRP and 95% if EPs were also considered. There was a mean of 2.64 (SD = 2.20) DRPs per patient and a mean of 2.14 (SD = 1.39) EPs per patient. Of these patients, 90% were over 65 years old or were treated with at least five chronic medications, two common criteria for identifying patients at risk of DRPs. The main types of DRPs were drug-drug interactions, compliance problems and duplicate drugs. Mean daily drug cost per patient was CHF 14.87 (US$10.70, 10.10). A potential savings of CHF 1.67 (US$1.20, 1.14) per day (11%) was estimated if all recommendations to solve DRPs and EPs suggested herein were implemented. CONCLUSION: Further studies should investigate whether the potential benefit of medication reviews in preventing DRPs and containing costs in this patient group can be confirmed in a real practice environment.