Efficacy on climacteric symptoms and safety of low dose estradiol transdermal matrix patches. A randomized, double-blind placebo-controlled study

Two estradiol (E2) transdermal patches releasing 25 micrograms/day E2 (D-25) or 37.5 micrograms/day E2 (D-37.5) were compared to a placebo patch on 156 patients in natural or surgical menopause suffering from at least 5 hot flushes per day, randomly and blindly assigned to three parallel groups of 52 patients each, to be treated continuously for 12 weeks, without progestin opposition. "Responders" (patients with less than 3 hot flushes per day at the end of treatment), were 82% and 90% under D-25 or D-37.5, respectively, both significantly (p < 0.001) more than under placebo (44%). Comparable efficacy was observed on severity of hot flushes, Kupperman Index and on the self-rated efficacy. Systemic adverse events occurred in 10%, 10% and 8% of patients, respectively, under D-25, D-37.5 or placebo. Occasional mild and transient itching and/or erythema on the site of application was reported by few patients and did never require discontinuation of application. In conclusion D-25 and D-37.5 were significantly more effective than placebo in relieving climacteric symptoms and were systemically and locally as well tolerated as placebo. D-25 (Demestril 25) releasing 25 micrograms/day E2 can therefore be recommended for low-dosed estrogen replacement therapy.     

Efficacy and safety of amisulpride 50 mg versus paroxetine 20 mg in major depression: a randomized, double-blind, parallel group study.

The efficacy of amisulpride in depressive disorders has been demonstrated in dysthymia and in double depression. Limited data are available in major depression. A randomized, double-blind, parallel group, multicentre study was set up to compare the efficacy and tolerability of amisulpride (50 mg o.d.) and paroxetine (20 mg o.d.) for 8 weeks in 272 patients with major depression (DSM-IV and baseline Hamilton Depression Rating Scale (HAMD) score > or = 18). The study was designed as a non-inferiority trial based on the proportion of responders (> or = 50% decrease in HAMD total score) at end-point, with a maximal allowable difference of 15%; secondary end-points included HAMD total and cluster scores, Montgomery and Asberg Depression Rating Scale score and responders rates and Clinical Global Impression improvement. The tolerability evaluation was based on incidence of adverse events and routine laboratory tests. The results did not disclose statistically significant differences between treatments, although the hypothesis of an efficacy difference between the two treatments within the set limit at day 56 could not be accepted. The issue of non-inferiority trials is discussed.     

Combined medical treatment using dutasteride and tamsulosin for lower urinary tract symptoms suggestive of benign prostatic hyperplasia

Importance of the field: Benign prostatic hyperplasia (BPH) is the fourth most commonly diagnosed medical condition in the elderly. Selective α-blockers (tamsulosin) and dual 5α-reductase inhibitors (dutasteride) have an important role in the medical treatment of symptomatic BPH. Safety and efficacy of combination therapy with dutasteride and tamsulosin as well as long-term benefit on prevention of disease progression have been widely studied in recent trials.

Areas covered in this review: The present article summarizes the pharmacologic properties of both dutasteride and tamsulosin. Clinical efficacy of combination therapy in different trials has also been reported. Major randomized trials on this concept published between 2000 and 2010 have been covered in this article.

What the reader will gain: Long-term efficacy and safety of combination therapy and its beneficial effect on quality of life and risk reduction of need for BPH-related surgeries have been discussed.

Take home message: Combination therapy with dutasteride and tamsulosin is a highly efficacious medical treatment in patients with moderate-to-severe lower urinary tract symptoms due to benign prostatic enlargement, which could be safely tolerated and administrated for ≥ 4 years.     

Efficacy and safety of escitalopram versus citalopram in major depressive disorder: a 6-week, multicenter, randomized, double-blind, flexible-dose study

Rationale

S-citalopram (escitalopram) is the very active moiety of citalopram. It has been shown in many studies to be an effective and safe antidepressant for treating major depressive disorder (MDD).

Objective

The aim of our study was to compare the efficacy and safety of escitalopram vs citalopram in Chinese MDD patients.

Methods

In the double-blind study, 240 MDD patients were randomly assigned to treatment for 6 weeks either with escitalopram (10?C20?mg/d) or citalopram (20?C40?mg/d). The primary efficacy measurement was the change of 17-item Hamilton Depression Rating Scale (HAMD-17) total score from baseline to the end of study. The secondary efficacy measurements were response and remission rates. The adverse events (AEs) were recorded by the investigator.

Results

Two hundred and three (85%) patients completed the trial. The average dose was 13.9?mg/d in the escitalopram group and 27.6?mg/d in the citalopram group. No significant differences were found between the two groups in the change in HAMD-17 total score, response, and remission rate. These results were similar in severe MDD patients. No significant differences were found between the two groups in AEs. No serious AEs were observed in this study.

Conclusions

The study suggests that escitalopram 10?C20?mg/d are as effective and safe as citalopram 20?C40?mg/d in the short-term treatment for Chinese MDD patients.     

Efficacy and safety of coenzyme A versus fenofibrate in patients with hyperlipidemia: a multicenter,double-blind,double-mimic,randomized clinical trial

Abstract

Background: We investigated the lipid-lowering efficacy and safety of coenzyme A (CoA) versus fenofibrate in Chinese patients with moderate dyslipidemia.

Methods: A total of 417 subjects (aged 18–75?years) diagnosed with moderate dyslipidemia (triglyceride 2.3–6.5?mmol/L) from 13 large cardiovascular centers in China were recruited and randomly divided into a fenofibrate group (n?=?207), which received 200?mg of fenofibrate orally once daily, and a CoA group (n?=?210), which received 400?mg of CoA orally once a day. Blood lipoproteins, liver and renal function, creatine kinase, and blood glucose were measured at baseline, and after 4 and 8?weeks of treatment.

Results: The baseline triglyceride (TG) level in the fenofibrate group and the CoA group was 3.39?±?0.99?mmol/L and 3.60?±?1.11?mmol/L, respectively. After treatment for 4 and 8?weeks with fenofibrate, TG was reduced by 31.62% and 33.13%. In the CoA group, TG was reduced by 17.29% and 23.80%. Compared with baseline, total cholesterol (TC) was significantly decreased in both groups after either 4 or 8?weeks of treatment (p?<?.05). CoA increased high-density lipoprotein cholesterol (HDL-C) after 4?weeks of treatment, whereas it had no significant effect on HDL-C after 8?weeks of treatment. Low-density lipoprotein cholesterol (LDL-C) was not modified in either group. The incidence of side effects was significantly lower in the CoA group compared with the fenofibrate group (p?<?.05).

Conclusions: Compared with fenofibrate, CoA has less effect on reducing plasma TG levels in subjects with moderate dyslipidemia. However, it has fewer adverse effects.     

西地那非治疗良性前列腺增生症所致下尿路症状的疗效

目的 观察西地那非治疗前列腺增生症（BPH）所致下尿路症状（LUTS）的临床疗效及安全性.方法 将经导入期后符合本试验研究的90例BPH所致LUTS并伴有勃起功能障碍（ED）的患者完全随机分成治疗组45例、对照组45例.治疗组口服西地那非100 mg/次,1次/d;对照组服用外型相同的安慰剂1片/次,1次/d,2组均用药8周.观察2组患者IPSS、最大尿流率（Qmax）、残余尿量等的改变,对LUTS进行评估;采用国际勃起功能评分（IIEF-5）对勃起功能进行评估,采用生活质量（QoL）评分评价BPH患者生活质量.结果 2组各有3例患者失访,末获任何评估结果,故实际试验患者数为84例.治疗8周后,对照组各项指标及治疗组的Qmax、残余尿量均有所改善,但差异无统计学意义（P＞0.05）;治疗组治疗后与治疗前比较IPSS、IIEF-5、QoL评分均明显改善（13.3分比17.5分,23.2分比15.2分,2.0分比4.9分,P＜0.05）.试验中,不良反应发生率治疗组为3例（7.1%）,对照组为2例（4.7%）,治疗组患者对西地那非耐受良好,不良反应轻微.结论 西地那非对治疗BPH所致LUTS有效、安全,尤其对BPH伴发ED患者具有较好的疗效.     

伐地那非治疗前列腺增生症所致下尿路症状的疗效

目的 观察伐地那非治疗良性前列腺增生症(BPH)所致下尿路症状(LUTS)的临床疗效.方法 国际前列腺症状评分(IPSS)≥12的BPH患者62例随机分为两组,每组31例.治疗组,口服伐地那非10 mg,每日两次;对照组服用安慰剂,疗程8周.比较治疗前后IPSS总分、最大尿流率(Qmax)、残余尿量(PVR),并行生活质量(QoL)和勃起功能评估.结果 与对照组比较,治疗8周后,治疗组IPSS值明显下降,国际勃起功能评分5(IIEF-5)明显增加,QoL明显改善(P<0.05).结论 伐地那非治疗BPH所致LUTS安全、有效.     

加替沙星注射液治疗急性下呼吸道感染的多中心双盲随机对照临床研究

目的　评价国产加替沙星注射液治疗急性下呼吸道感染的临床疗效与安全性。方法　采用多中心、双盲、随机对照试验设计 ,以左氧氟沙星注射液为对照药 ,两组均为 2 0 0 mg静脉滴注 ,Q12 h,疗程 7～ 10 d。结果　本研究共纳入 16 2例 ,加替沙星组和左氧氟沙星组分别为 82例和 80例 ,其中加替沙星组进行 ITT分析 80例 ,PP分析 70例 ,左氧氟沙星组进行 ITT分析 75例 ,PP分析 6 6例。疗程结束时加替沙星组与左氧氟沙星组的总痊愈率和有效率分别为 4 8.5 7%与 37.88%和 81.4 3%与 72 .73% ,两组细菌清除率分别为98.36 %和 98.2 8% ;治疗结束后 7d随访 ,两组的总痊愈率和有效率分别为 6 6 .6 4 %与 6 0 .6 0 %和 86 .92 %与89.39%。以上结果两组间比较及疗程结束时与结束后 7d比较 ,均无统计学差异。加替沙星组和左氧氟沙星组的不良反应发生率分别为 2 2 .5 0 %和 2 5 .33% ,均主要表现为轻度恶心、呕吐、头晕、失眠、局部刺激及肝功转氨酶增高等。结论　国产加替沙星注射液治疗急性下呼吸道感染疗效确切 ,安全性较好。     

Efficacy and safety of oral betaine glucuronate in non-alcoholic steatohepatitis. A double-blind, randomized, parallel-group, placebo-controlled prospective clinical study

In a prospective, randomized, double-blind therapeutic trial, 191 patients with non-alcoholic steatohepatitis were treated for 8 weeks daily b.i.d. orally either with betaine glucuronate combined with diethanolamine glucuronate and nicotinamide ascorbate (Ietepar) (96 patients) or with undistinguishable placebo capsules (95 patients). The verum treatment effectively reduced by 25% hepatic steatosis (p < 0.01) and by 6% hepatomegaly (p < 0.05), while placebo did not significantly reduce the disorders. Verum was also more effective than placebo on discomfort in abdominal upper right quadrant. The global efficacy of treatment was rated by the doctor "very good" or "good" in 48% of verum treated patients and only in 17% after placcbo (P of difference = 9 x 10(-6)). 52% of patients self-rated efficacy as "very good" or "good" after verum and only 34% after placebo (P of difference = 0.017). The verum treatment provoked a significant reduction of the increased liver transaminases (ALT, AST and gamma-GT) while placebo was ineffective. Adverse events were recorded in 10% of verum-treated patients and in 7% under placebo (no significant difference). In both groups the adverse events were mild and transient, did not require treatment discontinuation and were undistinguishable from common symptoms of liver disorders. In conclusion, the 8-week treatment with betaine glucuronate combined with diethanolamine glucuronate and nicotinamide ascorbate was found effective in non-alcoholic steatohepatitis, a disorder for which the hitherto pharmacological interventions were poorly and inconsistently effective.     

Efficacy and safety of bisacodyl in the acute treatment of constipation: a double-blind, randomized, placebo-controlled study

Summary

Background

Although laxatives are a first‐line treatment for constipation, there are few randomized placebo‐controlled trials assessing their efficacy.

Aim

To determine the effect and safety of oral bisacodyl on stool frequency and consistency in patients with idiopathic constipation.

Methods

55 patients (age 19–89 years) with idiopathic constipation were recruited from eight primary care practices and randomized to receive bisacodyl, 10 mg once daily, or placebo, on three successive days following a 3‐day run‐in period. Patients recorded stool frequency and consistency and adverse events.

Results

In each treatment group, 27 patients were evaluable for efficacy. The mean number of stools per day was significantly greater in the bisacodyl‐treated group (1.8/day) compared with placebo (0.95/day) over the treatment phase (P = 0.0061). Mean stool consistency score improved from ‘hard’ (run‐in) to between ‘soft’ and ‘well‐formed’ during bisacodyl treatment, remaining between ‘moderately hard’ and ‘hard’ for placebo treatment (P < 0.0001). The investigator's global efficacy score was superior for the bisacodyl group compared with placebo. Both treatments were well tolerated. Serum electrolyte levels and incidence of adverse events were comparable between treatment groups.

Conclusions

Bisacodyl is effective and safe in improving stool frequency and consistency in acute treatment of idiopathic constipation.

     

国产头孢呋辛治疗下呼吸道、泌尿道感染的随机对照、多中心临床试验

目的　评价国产头孢呋辛和进口头孢呋辛治疗感染性疾病的疗效和安全性。方法　随机、对照、多中心研究 ,每组 6 0例 ,其中下呼吸道、泌尿道感染各 30例 ,两药剂量均为每次 1.5 g,q8h,静滴 ,疗程 7～14 d。结果　国产和进口头孢呋辛治疗下呼吸道感染的临床痊愈率分别为 70 %和 6 0 % ,有效率均为 93.3% ;治疗泌尿是感染痊愈率分别为 93%和 83% ,有效率均为 10 0 % ,细菌清除率国产头孢呋辛组 96 .4 % ;进口头孢呋辛组 96 .3%。国产和进口头孢呋辛组不良反应发生率分别为 1.7%和 3.3%。两组疗效和不良反应无统计学差异 (P>0 .0 5 )。结论　国产头孢呋辛治疗下呼吸道感染、泌尿道感染性疾病安全、有效 ,与进口产品等效。     

Combination therapy with tamsulosin and solifenacin for male lower urinary tract symptoms with predominant filling symptoms: a new approach to an old problem

Benign prostatic enlargement is the main cause of male lower urinary tract symptoms (LUTS). The distinction and quantification of voiding, storage and postmicturition symptoms help clinicians decide on a modern pharmacological therapeutic approach for male LUTS. Muscarinic receptors antagonists are now considered safe therapy in males and a fixed-dose combination of oral controlled absorbed system solifenacin and tamsulosin is advantageous compared to tamsulosin monotherapy in males with predominant storage symptoms when validated instruments such as International Prostatic Score Symptoms (IPSS) or Total Urgency Frequency Score (TUFS) are used. This combination therapy is well tolerated and maintains symptomatic improvement in the long term. Different options of managing male LUTS with predominant storage symptoms include a combination of tamsulosin and solifenacin, antimuscarinics alone – some with flexible dosing, and the beta-3 agonist mirabegron. Tailored pharmacological therapy for the particular patient is not a reality yet, but judicious use of the different alternatives could bring varied new therapeutic solutions for male LUTS including benign prostatic enlargement and benign prostatic obstruction.     

Oral versus combination mesalazine therapy in active ulcerative colitis: a double-blind, double-dummy, randomized multicentre study

BACKGROUND: Oral and topical mesalazine formulations are effective in active ulcerative colitis, but little is known on the efficacy of combined treatment. AIM: To compare the efficacy of oral mesalazine vs. combined oral and topical mesalazine in mildly to moderately active ulcerative colitis. METHODS: Patients with mildly to moderately active ulcerative colitis (Clinical Activity Index, CAI 4-12) were identified at 15 participating centres. They were randomized to receive either mesalazine 4 g orally plus placebo enema, or mesalazine 2 g orally plus mesalazine 2 g rectally as a liquid enema for 6 weeks. The rate of clinical remission (CAI < 4) or clinical remission/improvement (reduction of CAI of 50% from baseline) at 6 weeks and time to clinical remission/improvement were primary end-points; the rate of endoscopic remission was a secondary end-point. RESULTS: 67 patients were assigned to oral treatment and 63 to combined treatment. One patient in the oral group and 2 in the combined group discontinued the treatment due to adverse events. Following an intention-to-treat analysis, the rate of clinical remission was 82% for oral treatment and 87% for combined treatment (P=0.56); the mean time to remission 22.2 and 20.2 days, respectively (P=0.29); the rate of clinical remission/improvement and the rate of endoscopic remission were 85% and 91% (P=0.503) and 58% and 71% (P=0.21), respectively. CONCLUSIONS: In patients with mild active ulcerative colitis, mesalazine 4 g orally and 2 g orally plus 2 g enema are equally effective in inducing disease remission.     

加巴喷丁治疗偏头痛的有效性和安全性——随机、双盲对照研究

目的：评价加巴喷丁治疗偏头痛的有效性及安全性。方法：采用随机、双盲、安慰剂平行对照研究,为期8周,共有104例偏头痛患者（年龄18～60岁）被随机分至治疗组和对照组。治疗组：55例,接受加巴喷丁治疗4周;对照组：49例,口服安慰剂4周。在开始治疗时及治疗后4周、8周时采用数字评价量表对患者的疼痛程度进行评估,同时监测患者的肝肾功能、经颅多普勒超声（TCD）、脑电图（EEG）及药物不良反应。结果：4周后加巴喷丁治疗组患者头痛发生率（次/月）、持续时间（h）、疼痛程度（分）均明显下降,分别由6.4±2.5降至2.3±1.5、21.8±12.6下降至8.6±4.3、8.6±1.2降至2.4±1.1。与对照组比较,差异有统计学意义（P〈0.01）。而不良反应轻微,其发生率与对照组比较差异无统计学意义（P〉0.05）。结论：加巴喷丁能有效降低偏头痛的发作次数、疼痛程度及疼痛持续时间,而不良反应轻微,安生性较高。     

Interrelation of erectile dysfunction and lower urinary tract symptoms

The association between erectile dysfunction (ED) and lower urinary tract symptoms (LUTS) has garnered attention as investigators have hypothesized a common pathophysiology to explain the assertion that they are causally linked. This relationship between LUTS and ED has received increased attention because both diseases are highly prevalent, frequently co-associate in the same aging male group, and significantly influence the overall quality of life. A causal association between LUTS and ED cannot be established on the basis of the ever-increasing number of epidemiological studies. Attempting to explain a causal relationship between ED and LUTS requires the use of Hill's criterion, which is used by many epidemiologists to separate causal from non-causal explanations. A review of the epidemiological evidence reveals a strong degree of association, internal consistency and dose response effects between ED and LUTS. The temporal relationships between the two remain unknown because of the strong cross-sectional flavor of the epidemiological studies. The issue of an "alternate explanation" to describe the LUTS-ED association appears to be accounted for in that several large studies have provided convincing multiple regression analyses in which the ED-LUTS relationship remains significant. Biologic plausibility is an important issue if the link between ED and LUTS is to have credence. There are four leading theories of how these diseases interrelate. These explanations have a variable amount of supporting data. These include: 1) autonomic hyperactivity effects on LUTS, prostate growth and ED; 2) nitric oxide synthase/nitric oxide levels decreased or altered in the prostate and penile smooth muscle; 3) prostate and penile ischemia; and 4) increased Rho-kinase activation/ endothelin activity. LUTS and sexual dysfunction are highly prevalent in aging men. Both conditions are also significant contributors to overall quality of life. New data has emerged to indicate potential links in epidemiological, physiologic, pathophysiologic and treatment aspects of these two diseases. Using Hill's causality method to separate causal from non-causal explanations linking ED with LUTS, it appears that most epidemiological components are fulfilled.     

巴洛沙星片治疗泌尿系统细菌感染性疾病多中心、随机、双盲、阳性药平行对照临床试验

目的评价国产巴洛沙星片治疗轻、中度泌尿系统细菌感染性疾病的临床疗效与安全性。方法采用多中心、双盲双模拟、平行、随机阳性药对照实验设计。以左氧氟沙星为对照药。巴洛沙星为试验药。巴洛沙星100mg&#183;每日2次；左氧氟沙星200mg，每日2次．疗程均为7～10d。结果本研究人组病例数共210例。巴洛沙星组及左氧氟沙星组各105例，其中巴洛沙星组FAS分析104例．PPS分析100例；左氧氟沙星组FAS分析103例，PPS分析103例。疗程结束时，FAS分析巴洛沙星组的痊愈率和有效率分别为69．23％和95．19％。左氧氟沙星组的痊愈率和有效率分别为67．96％和97．09％；PPS分析巴洛沙星组的痊愈率和有效率分别为70．00％和97．00％，左氧氟沙星组的痊愈率和有效率分别为67．96％和97．09％；两组的痊愈率和有效率无明显统计学差异（P〉0．05）。两组细菌清除率分别为93．18％和90．70％，两组组间比较也无显著性差异（P〉0．05）。不良反应主要表现为白细胞减少、胃肠道反应、直接胆红紊升高、尿检异常。两组无显著性差异（P〉0．05）。两组均未见严重不良事件发生。结论国产巴洛沙星片治疗泌尿系统轻、中度感染疗效确切，安全性好。