拉莫三嗪单药治疗各型癫癎的开放性自身对照临床研究

目的:评价拉莫三嗪(LTG)单药治疗不同类型癫癎发作的临床疗效和安全性.方法:收集单独应用LTG或原用其他抗癫癎药(AED)转换成LTG单药治疗58例各型癫癎发作病例,并进行开放性自身对照研究. 结果:41例中总有效率为80.49%,其中失神性癫癎有效率为100%.另17例服用其它AED已控制发作,转换为LTG单药治疗后也无复发.追踪1～3年,仍单用LTG且有效者占74.36%,平均剂量为4.12±1.50 mg/(kg·d-1),平均血药浓度为3.05±1.13 μg/ml,剂量与浓度呈直线相关(P<0.01).不良反应率为13.79%,主要表现为皮疹和偏头痛. 结论:LTG单药治疗各型癫癎发作均有效,尤以失神性发作型为著,不良反应发生率低且轻微.     

Reno protective role of amlodipine in patients with hypertensive chronic kidney disease

Chronic kidney disease (CKD) and hypertension (HTN) are closely associated with an overlapping and intermingled cause and effect relationship. Decline in renal functions are usually associated with a rise in blood pressure (BP), and prolonged elevations in BP hasten the progression of kidney function decline. Regulation of HTN by normalizing the BP in an individual, thereby slowing the progression of kidney disease and reducing the risk of cardiovascular disease, can be effectively achieved by the anti-hypertensive use of calcium channel blockers (CCBs). Use of dihydropyridine CCBs such as amlodipine (ALM) in patients with CKD is an attractive option not only for controlling BP but also for safely improving patient outcomes. Vast clinical experiences with its use as monotherapy and/or in combination with other anti-hypertensives in varied conditions have demonstrated its superior qualities in effectively managing HTN in patients with CKD with minimal adverse effects. In comparison to other counterparts, ALM displays robust reduction in risk of cardiovascular endpoints, particularly stroke, and in patients with renal impairment. ALM with its longer half-life displays effective BP control over 24-h, thereby reducing the progression of end-stage-renal disease. In conclusion, compared to other classes of CCBs, ALM is an attractive choice for effectively managing HTN in CKD patients and improving the overall quality of life.     

A Phase II Open-Label Study of Ganetespib,a Novel Heat Shock Protein 90 Inhibitor for Patients With Metastatic Breast Cancer

BackgroundGanetespib is a small molecule, nongeldanamycin HSP90 inhibitor with potent inhibitory effects on HSP90-dependent oncoproteins of relevance to breast cancer pathogenesis. We therefore tested ganetespib in an unselected cohort of patients with MBC.Patients and MethodsPatients were treated with single agent ganetespib at 200 mg/m² once weekly for 3 weeks, on a 28-day cycle. Therapy was continued until disease progression. The primary end point was ORR using Reponse Evaluation Criteria in Solid Tumors version 1.1.ResultsTwenty-two patients were enrolled with a median age of 51(range, 38-70) years and a median Eastern Cooperative Oncology Group performance status of 0 (range, 0-1). Most patients had at least 2 previous lines of chemotherapy in the metastatic setting. Most common toxicities, largely grade 1/2, were diarrhea, fatigue, nausea, and hypersensitivity reaction. The ORR in this unselected population was 9%, with all responses coming from the subset of patients with HER2-positive MBC (2/13; 15%). One patient with TNBC had objective tumor regression in the lung metastases. The clinical benefit rate (complete response + partial response + stable disease > 6 months) was 9%, median progression-free survival was 7 weeks (95% confidence interval [CI], 7-19), and median overall survival was 46 weeks (95% CI, 27-not applicable).ConclusionThe study did not meet the prespecified criteria for ORR in the first stage of the Simon 2-stage model in this heavily pretreated unselected population of MBC. However, activity was observed in trastuzumab-refractory HER2-positive and TNBC. Ganetespib was well tolerated and responses in more targeted populations harboring specific HSP90-dependent oncoproteins justifies its further study, particularly as part of rational combinations.     

Success of electromagnetic shock wave lithotripter as monotherapy in large renal calculi—Our experience

ObjectivesTo evaluate the success of shock wave lithotripsy (SWL) as monotherapy for solitary renal stones larger than 2 cm without ureteral stenting. Hence, if our study result demonstrates acceptable success and safety, we can recommend ESWL as a treatment option for patients with large renal calculi.Subjects and methodsThis is a prospective study conducted in the Department of Urology, Regional Institute of Medical Sciences, Imphal, India, from January 2011 to December 2012. A total of 104 patients aged between 20 and 70 years with solitary large (>2 cm) renal stones underwent ESWL using the Dornier Compact Sigma Lithotripter. Stone size was calculated by measuring the largest dimension of the stone in KUB plain films. In each session, 3000–3500 shocks at frequency 60–90 min^?1 and intensity between 1 and 4 were given. A maximum number of six sessions were given. Successful treatment was defined as complete clearance or residual stones smaller than 4 mm on KUB performed 3 months after the first session.ResultsTotal number of patients was 104. The M:F ratio was 1:1.4. The stone size ranged from 21 to 55 mm. The overall success rate was 73%. For stones >30 mm, the success rate was only 62.2% (n = 28). The number of sessions required increased as the stone size increased. The most common complication encountered was haematuria.ConclusionESWL remains the cornerstone of therapy for renal calculi less than 2 cm. Our study reveals that multiple sessions were required for solitary renal calculi, with higher rate of ancillary procedures. The success rate of ESWL for both non-staghorn and staghorn calculi with size above 2 cm is low, so other treatment modalities like PCNL should be considered as the first treatment option. However, with appropriate patient selection, significant improvements in stone-free rates may be achieved.     

浙江大学儿童医院左乙拉西坦片处方分析

目的:分析我院门诊左乙拉西坦片使用情况,为合理用药提供参考.方法:对我院门诊2010年11 ～12月左乙拉西坦片电子处方进行统计,分析用药合理性.结果:共检索到目标处方269张,涉及患儿208例.4岁以下患儿处方65张,占总处方的24.16％;诊断为癫痫的处方256张,占95.17％;18岁以下体重小于50kg的患儿处方266张,其中单次剂量小于10 mg/(kg·次)的处方65张,占24.44％;左乙拉西坦单药治疗的患儿占32.69％.结论:我院左乙拉西坦应用无年龄限制;临床诊断与用法用量基本合理;左乙拉西坦单药治疗癫痫有一定应用;电子处方系统需要优化或细分;建议配备更适合儿童应用的剂型;用于4岁以下患儿或单药治疗时建议从用药的安全性、有效性方面充分权衡利弊,以达到合理用药.     

Degree of control and delayed intensification of antihyperglycaemic treatment in type 2 diabetes mellitus patients in primary care in Spain

Objectives

Primary aim: to determine the degree of control of HbA_1c at the time of treatment intensification (TI) in T2DM patients. Secondary aims: fasting plasma glucose levels; estimation of the elapsed time between HbA_1c exceeding 7% and TI; antidiabetic combinations used, % patients with good cardiometabolic control (LDL-c < 100 mg/dL; SBP < 130 and DPB < 80 mmHg and HbA_1c < 7%).

Research design and methods

One-cohort, multicenter, retrospective, observational study conducted in Spain. Patients diagnosed with T2DM that had switched from monotherapy to combination antidiabetic therapy were evaluated at baseline and after one year of follow-up.

Results

A total of 1202 T2DM patients were analyzed. At the time of TI: mean HbA_1c 8.1%; median time of uncontrolled disease: 2.0 years. After one-year of TI: significant reduction in mean HbA_1c (8.1% vs.7.0%, p < 0.001) and a mean fasting plasma glucose levels reduction (181.1 mg/dL vs.144.1 mg/dL, p < 0.001) was also observed. The percentage of patients under glycemic control (HbA_1c < 7%) increased from 12.2% to 51.6% (p < 0.001). Most common antidiabetic combinations: metformin + sulfonylurea (44.1%) and metformin + thiazolidindione (15.9%).

Conclusions

In the population of T2DM patients analyzed, TI was carried out when HbA_1c values were above those recommended in clinical guidelines (≤7%), with a delay of two years to address the second step of therapy, despite the consensus recommendation of the ADA/EASD of 3 months. TI was shown to be effective since addition of a second antidiabetic drug led to an average reduction of HbA_1c of approximately 1%. Metformin was the drug most commonly used as monotherapy being the most frequent combination metformin + sulfonylurea.     

Antiepileptic drug use during pregnancy: Perinatal outcomes

Purpose

This study was undertaken to (1) measure the frequency of AED monotherapy or polytherapy during pregnancy and AED discontinuation prior to pregnancy in a cohort of women with treated epilepsy; and (2) describe the frequency of major congenital malformations according to maternal use of AED during pregnancy.

Methods

A cohort of epileptic pregnant women was identified within the Quebec Pregnancy Registry and was divided into three groups based on maternal AED use during pregnancy: AED monotherapy, AED polytherapy and no AED use.

Results

Of the 349 pregnancies meeting eligibility criteria, 79.6% were exposed to AED monotherapy and 5.8% to polytherapy during pregnancy; 14.6% discontinued AED prior to pregnancy. The most commonly used AEDs were carbamazepine (29.9%) and valproic acid (19.7%); the most common AED polytherapy combination was carbamazepine combined with clobazam (2.5%). Of 111 deliveries in the group of women on monotherapy during pregnancy, 9.9% (n = 11) were born with major congenital malformations; in the group of women treated with polytherapy, 19.0% (n = 8 over 42) of babies had major congenital malformations compared to 20.0% in women who discontinued AEDs prior to pregnancy.

Conclusion

This study demonstrates that the majority of women suffering from epilepsy were treated with monotherapy rather than polytherapy during pregnancy. While most used other agents, an important number of women continued to use valproate in pregnancy despite the long standing evidence of its teratogenicity and increasing evidence of its neuro-toxicity to the fetus.     

Prescribing practices in psychiatric hospitals in Eastern Europe

Background

There has been no evidence about the prescribing practices in psychiatric care in Eastern Europe.

Aims

To examine the patterns of psychotropic prescribing in five countries of Eastern Europe.

Method

We conducted a one-day census of psychiatric treatments used in eight psychiatric hospitals in Albania, Croatia, Macedonia, Serbia and Romania. We examined clinical records and medication charts of 1304 patients.

Results

The use of polypharmacy was frequent across all diagnostic groups. Only 6.8% of patients were on monotherapy. The mean number of prescribed drugs was 2.8 (SD 0.97) with 26.5% receiving two drugs, 42.1% receiving three drugs and 22.1% being prescribed four or more psychotropic drugs. Typical antipsychotics were prescribed to 63% and atypical antipsychotics to 40% of patients with psychosis. Older generations of antidepressants were prescribed to 29% of patients with depression. Anxiolitic drugs were prescribed to 20.4% and benzodiazepines to 68.5% of patients. One third of patients received an anticholinergic drug on a regular basis.

Conclusions

Older generation antipsychotics and antidepressants were used more frequently than in the countries of Western Europe. Psychotropic polypharmacy is a common practice. There is a need for adopting more evidence-based practice in psychiatric care in these countries.