Amantadine for dyskinesias in Parkinson's disease: a randomized controlled trial

Background

Dyskinesias are some of the major motor complications that impair quality of life for patients with Parkinson''s disease. The purpose of the present study was to investigate the efficacy of amantadine in Parkinson''s disease patients suffering from dyskinesias.

Methods

In this multi-center, double-blind, randomized, placebo-controlled, cross-over trial, 36 patients with Parkinson''s disease and dyskinesias were randomized, and 62 interventions, which included amantadine (300 mg /day) or placebo treatment for 27 days, were analyzed. At 15 days after washout, the treatments were crossed over. The primary outcome measure was the changes in the Rush Dyskinesia Rating Scale (RDRS) during each treatment period. The secondary outcome measures were changes in the Unified Parkinson''s Disease Rating Scale part IVa (UPDRS-IVa, dyskinesias), part IVb (motor fluctuations), and part III (motor function).

Results

RDRS improved in 64% and 16% of patients treated with amantadine or placebo, respectively, with significant differences between treatments. The adjusted odds-ratio for improvement by amantadine was 6.7 (95% confidence interval, 1.4 to 31.5). UPDRS-IVa was improved to a significantly greater degree in amantadine-treated patients [mean (SD) of 1.83 (1.56)] compared with placebo-treated patients [0.03 (1.51)]. However, there were no significant effects on UPDRS-IVb or III scores.

Conclusions

Results from the present study demonstrated that amantadine exhibited efficacious effects against dyskinesias in 60–70% of patients.

Trial Registration

UMIN Clinical Trial Registry UMIN000000780     

凉血止痢汤与锡类散保留灌肠治疗溃疡性结肠炎的疗效对比

目的:观察凉血止痢汤与锡类散保留灌肠治疗溃疡性结肠炎的疗效。方法:选取80例溃疡性结肠炎患者,按随机数字表法分为两组,对照组(39例)给予锡类散治疗,观察组给予凉血止痢汤治疗,观察两组治疗后的疗效,腹痛、腹泻、脓血便消失时间,治疗前后C反应蛋白、白细胞、血红蛋白数目及治疗期间不良反应情况。结果:治疗后,两组治疗有效率比较无明显差别(P0.05),观察组患者腹痛、腹泻、脓血便消失时间均短于对照组(P0.05),两组组白细胞数目、C反应蛋白水平均较治疗前显著下降且观察组上述指标较对照组更低(P0.05)。两组血红蛋白数目均较治疗前显著上升且观察组较对照组更高(P0.05)。两组治疗期间均无肝肾功能异常、胃肠道异常等不良反应发生。结论:凉血止痢汤与锡类散联合对溃疡性结肠炎均具有较好的治疗效果,能更快消退溃疡性结肠炎症状,且安全性高。     

Objective assessment of antianginal treatment: a double-blind comparison of propranolol,nifedipine, and their combination.

In a double-blind clinical trial the antianginal effects of nifedipine (30 and 60 mg/day) and propranolol 240 and 480 mg/day) and a combination of both drugs were compared with those of placebo in 16 patients with severe exertional angina pectoris. Response to treatment was assessed by the objective criteria of 16-point precordial exercise mapping and 48-hour ambulatory electrocardiographic monitoring and subjectively by analysis of patients'' daily diaries of episodes of angina and consumption of glyceryl trintrate. The incidence of pain and consumption of glyceryl trinitrate were significantly decreased by each drug compared with placebo, and the combination produced a further significant improvement. Objectively the total area and amount of ST depression on the precordial exercise map and the total number of episodes of ST depression detected on ambulatory monitoring confirmed the efficacy of each treatment regimen; the combination was significantly better than either drug alone (p <0.005). The objective methods permitted greater separation of treatment efficacy and showed reliably that the combination of propranolol and nifedipine was significantly better than either drug alone. Thus this combination is a safe and effective form of treatment for angina.     

Long-term therapy of Parkinson's disease with amantadine,alone and combined with levodopa

A dual study was conducted to assess (1) the long-term antiparkinsonian action of amantadine without levodopa and (2) the advantage of combined amantadine and levodopa over single-drug therapy, including changes in symptom severity when placebo replaces amantadine but levodopa is maintained.Good to excellent results were obtained in 25% of the total pool of 77 patients on amantadine. No decline in therapeutic effect took place during a mean follow-up of 21 months.Thirty-seven patients with considerable residual deficit after single-drug therapy derived improvement from the second drug (levodopa or amantadine). Gains in neurological signs and activities of daily living (ADL) ranged between 50 and 60% and for timed skills close to 25%. Depending on the individual indices, between 64 and 100% of patients improved with the second drug.Placebo instead of amantadine produced deterioration. There was 75% loss in ADL, 45% loss in timed skills and losses in neurological signs exceeded gains produced by two-drug therapy.     

复方苦参注射液联合盐酸羟考酮缓释片治疗卵巢癌患者癌痛的临床研究

目的:探讨盐酸羟考酮缓释片联合复方苦参注射液对卵巢癌患者癌痛的影响。方法:选择我院2015年1月至2018年6月收治的77例卵巢癌患者,随机分为观察组(39例)及对照组(38例)。对照组给予羟考酮缓释片,观察组在对照组基础上加用复方苦参注射液,对比两组治疗前和治疗1个疗程后的疼痛数字评分(Numerical rating scale,NRS)评分和生活质量评分的变化,治疗期间每人每天的羟考酮用量及不良反应的发生情况。结果:治疗后,两组NRS评分均较治疗前明显下降,且观察组NRS评分明显低于对照组(P0.05)。治疗后,观察组的疲乏、恶心呕吐、疼痛、食欲丧失、便秘评分明显低于对照组(P0.05)。观察组每人每天羟考酮的用量、便秘及不良反应总发生率明显低于对照组(P0.05)。结论:复方苦参注射液联合羟考酮可有效缓解卵巢癌的癌痛,降低羟考酮毒副作用,提高患者的生活质量。     

Intravenous Amantadine for Freezing of Gait Resistant to Dopaminergic Therapy: A Randomized,Double-Blind,Placebo-Controlled,Cross-Over Clinical Trial

Background

Freezing of gait (FOG) is one of the most disabling symptoms in Parkinsonism. Open-label studies have suggested that intravenous (IV) amantadine is effective against FOG resistant to dopaminergic therapy in Parkinson''s disease (PD). We evaluated the efficacy of IV amantadine on FOG resistant to dopaminergic therapy.

Methodology/Principal Findings

This was a randomized, double-blind, placebo-controlled, cross-over study on IV amantadine. The placebo (normal saline) and amantadine (400 mg/day) were injected for 2 days with a 52-hour washout period. The instruments for the outcome measures were the Freezing of Gait Questionnaire (FOGQ), Unified Parkinson''s disease rating Scale (UPDRS), and the duration of the 4×10 m walking test. The placebo arm was compared to the amantadine arm. Ten patients were enrolled but two patients withdrew, one from each arm. The FOGQ and UPDRS scores and the duration of the 4×10 m walking test improved in both arms compared to the baseline (P<0.05 in all). However, there were no differences in these values between the amantadine arm and placebo arm (P = 0.368, P = 0.583, P = 0.206, respectively). Follow-up measures 2weeks after discharge in an open-label study showed the beneficial effects of an amantadine tablet on FOG (FOGQ, P = 0.018; UPDRS, P = 0.012 respectively).

Conclusions/Significance

This double blind, placebo-controlled study did not show the efficacy of IV amantadine on FOG when compared with the placebo. This study provides Class II evidence due to small sample size for the lack of benefit of IV amantadine on FOG resistant to dopaminergic therapy

Trial Registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01313819","term_id":"NCT01313819"}}NCT01313819     

Use of Amantadine in Parkinson's Disease. Results of a Double-blind Trial

In a four-week double-blind trial of 62 patients with Parkinsonism 29 were treated withamantadine and 33 with a placebo. Modest but statistically significant improvement was observed in the first group, optimum benefit occurring after the first two weeks. Patients'' reactions to the drug were favourable in 79%, and side effects were insignificant. Though amantadine appears to be a useful additive drug in the treatment of Parkinsonism, its value as a single treatment is as yet undetermined.     

Randomised controlled comparative study of methyldopa and oxprenolol in treatment of hypertension in pregnancy.

One hundred pregnant women with hypertension (defined as diastolic blood pressure at or above 95 mm Hg) were allocated at random to treatment with methyldopa or oxprenolol and were compared with nonhypertensive controls matched according to parity and gestation at delivery. The patients were also stratified into those entering the study early (before 32 weeks'' gestation) and those entering late (after 32 weeks'' gestation). Although there were no differences in diastolic blood pressure between the hypertensive groups before or during treatment, in the early entry group the systolic blood pressure at entry of those allocated to oxprenolol was significantly higher than that of those receiving methyldopa; this difference remained throughout the treatment period. Also in the early entry group further increments of drug treatment were required to control blood pressure of patients receiving oxprenolol than in those receiving methyldopa. The eventual fetal outcome for all patients treated with methyldopa was the same as that for those treated with oxprenolol; birth weight, placental weight, head circumference, and Apgar score were not significantly different and there were no stillbirths in either group.     

The effect of Lactobacillus brevis KB290 against irritable bowel syndrome: a placebo-controlled double-blind crossover trial

ABSTRACT: BACKGROUND: Irritable bowel syndrome (IBS) is a functional disorder of the digestive tract that causes chronic abdominal symptoms. We evaluated the effects of Lactobacillus brevis KB290 (KB290), which has been demonstrated to be effective at improving bowel movements and the composition of intestinal microflora, on IBS symptoms. METHODS: We performed a placebo control double-blind cross matched trial. Thirty-five males and females (aged 6 years and above) who had been diagnosed with IBS according to the Rome III criteria were divided into 2 groups, and after a 4-week pre-trial observation period, they were administered test capsules containing KB290 or placebo for 4 weeks (consumption period I). Then, the capsule administration was suspended for 4 weeks in both groups (washout period), before the opposite capsules were administered for a further 4 weeks (consumption period II). Fecal samples were collected on the first day of the pre-consumption observation period, the last day of consumption period I, the last day of the washout period, and the last day of consumption period II. In addition, the subjects' IBS symptoms and quality of life (QOL) and any adverse events that they experienced were evaluated. RESULTS: No significant difference in IBS symptoms was noted among the various periods. However, the mean QOL scores were improved during the test capsule consumption. The frequencies of watery and mushy feces were significantly lower in the test capsule consumption period than during the pre-consumption observation period, and the frequency of abdominal pain was significantly reduced in the test capsule consumption period compared with the other periods. The frequency of the genus Bifidobacterium was significantly higher, and that of the genus Clostridium was significantly lower, after the test capsule consumption than after the placebo consumption. The frequencies of the genera Lactobacillus, Bacteroides, and Enterococcus were also investigated, but no differences in their frequencies were detected between the placebo and test capsule consumption periods. CONCLUSIONS: Probiotics, the safety of which has been established, are used widely in various foods and can now be purchased readily. The results of the present study suggest that KB290 is useful for early intervention in IBS.     

Randomized,Double-Blind,Crossover Trial of Amitriptyline for Analgesia in Painful HIV-Associated Sensory Neuropathy

We conducted a randomized, double-blind, placebo-controlled, crossover study at a single center in South Africa, to ascertain whether amitriptyline is an effective analgesic for painful HIV-associated sensory neuropathy of moderate to severe intensity in: i) antiretroviral drug naive individuals, and ii) antiretroviral drug users. 124 HIV-infected participants (antiretroviral drug naive = 62, antiretroviral drug users = 62) who met the study criteria for painful HIV-associated sensory neuropathy were randomized to once-daily oral amitriptyline (titrated to a median: interquartile range of 50: 25-50 mg) or placebo for six weeks, followed by a three-week washout period and subsequent treatment crossover. The primary outcome measure was change from baseline in worst pain intensity of the feet (measured by participant self-report using an 11-point numerical pain rating scale) after six weeks of treatment. 122 of 124 participants completed all study visits and were included in the analysis of the primary outcome. In the antiretroviral drug-naive group (n = 61) there was no significant difference in the mean change in pain score from baseline after six weeks of treatment with placebo or amitriptyline [amitriptyline: 2.8 (SD 3.3) vs. placebo: 2.8 (3.4)]. Similarly, there was no significant difference in the change in pain score after six weeks of treatment with placebo or amitriptyline in the antiretroviral drug-user group (n = 61) [amitriptyline: 2.7 (3.3) vs. placebo: 2.1 (2.8)]. Controlling for period effects and treatment order effects did not alter the outcome of the analyses. Nor did analyzing the intention-to-treat cohort (missing data interpolated using baseline observation carried forward) alter the outcome of the analyses. In summary, amitriptyline, at the doses used here, was no more effective than an inactive placebo at reducing pain intensity in individuals with painful HIV-associated sensory neuropathy of moderate to severe intensity, irrespective of whether they were on antiretroviral therapy or not.

Trial Registration

ISRCTN 54452526     

Oral acyclovir in acute herpes zoster.

Oral acyclovir at a dose of 800 mg five times daily for seven days was compared with placebo in a randomised double blind trial conducted at three centres in the United Kingdom. The study group comprised 205 elderly immune competent patients suffering from herpes zoster who were entered within 72 hours of the onset of rash. Acyclovir significantly reduced the times to arrest of new lesion formation (p = 0.005), loss of vesicles (p less than 0.001), and full crusting (p = 0.02) in those patients entered within 48 hours of the onset of rash. In addition, there was a significant reduction in pain during treatment with acyclovir as compared with placebo (p = 0.008). Of the patients with severe pain on entry, 40% (10/25) of those treated with acyclovir had no or only mild pain at the end of treatment, whereas in the placebo group all had residual moderate or severe pain (p less than 0.001). No clinically important adverse effects of acyclovir were reported. Oral acyclovir may modify acute herpes zoster and reduce pain.     

Does the cannabinoid dronabinol reduce central pain in multiple sclerosis? Randomised double blind placebo controlled crossover trial

Objective To evaluate the effect of the oral synthetic δ-9-tetrahydrocannabinol dronabinol on central neuropathic pain in patients with multiple sclerosis.Design Randomised double blind placebo controlled crossover trial.Setting Outpatient clinic, University Hospital of Aarhus, Denmark.Participants 24 patients aged between 23 and 55 years with multiple sclerosis and central pain.Intervention Orally administered dronabinol at a maximum dose of 10 mg daily or corresponding placebo for three weeks (15-21 days), separated by a three week washout period.Main outcome measure Median spontaneous pain intensity (numerical rating scale) in the last week of treatment.Results Median spontaneous pain intensity was significantly lower during dronabinol treatment than during placebo treatment (4.0 (25th to 75th centiles 2.3 to 6.0) v 5.0 (4.0 to 6.4), P = 0.02), and median pain relief score (numerical rating scale) was higher (3.0 (0 to 6.7) v> 0 (0 to 2.3), P = 0.035). The number needed to treat for 50% pain relief was 3.5 (95% confidence interval 1.9 to 24.8). On the SF-36 quality of life scale, the two items bodily pain and mental health indicated benefits from active treatment compared with placebo. The number of patients with adverse events was higher during active treatment, especially in the first week of treatment. The functional ability of the multiple sclerosis patients did not change.Conclusions Dronabinol has a modest but clinically relevant analgesic effect on central pain in patients with multiple sclerosis. Adverse events, including dizziness, were more frequent with dronabinol than with placebo during the first week of treatment.     

参麦注射液与布地奈德联合治疗急性酒精中毒伴吸入性肺炎的临床研究

目的:探究参麦注射液与布地奈德联合治疗急性酒精中毒伴吸入性肺炎的临床疗效。方法:选择2012年6月~2015年6月期间,我院收治急性酒精中毒合并吸入性肺炎患者112例为研究对象,采用随机数字法将其随机分为观察组(57例)和对照组(55例)。对照组在基础治疗的基础上给予布地奈德治疗,观察组在对照组的基础上联合参麦注射液治疗,收集并分析治疗后两组患者症状恢复时间、症状消失时间、清醒后不良反应发生情况、治疗前后肝功能指标及血清炎性因子指标。结果:观察组患者清醒时间、血压恢复时间及头晕、头痛、电解质紊乱的发生率均显著低于对照组(P0.05);治疗后两组患者间天冬氨酸氨基转移酶(AST)、丙氨酸转氨酶(ALT)、γ-谷氨酰基转移酶(GGT)水平均出现显著降低,且观察组均显著低于对照组(P0.05);观察患者咳嗽消失、气喘缓解、哮鸣音消失及湿罗音消失时间均显著低于对照组(P0.05);治疗后两组患者血清IL-6、TNF-α及CRP水平均显著降低,且观察组均显著低于对照组(P0.05)。结论:参麦注射液与布地奈德联合治疗急性酒精中毒伴吸入性肺炎疗效可靠,能够有效缩短患者酒精中毒症状的恢复与消失时间,降低清醒后不良症状的发生率,并且能改善患者肝功能、减轻炎症反应,具有重要的临床价值。     

The case for low dose diuretics in hypertension: comparison of low and conventional doses of cyclopenthiazide.

In a double blind placebo controlled randomised parallel study the antihypertensive activity and adverse biochemical effects of three doses of cyclopenthiazide were evaluated in patients with mild essential hypertension that had been recently diagnosed or was being treated with a single drug. After a four week placebo washout period 53 patients with diastolic blood pressures between 90-110 mm Hg were randomly assigned to 50, 125, or 500 micrograms cyclopenthiazide or matching placebo for an eight week period of treatment. Blood pressure was measured in the patients'' homes by the same observer every two weeks. Serum urea, electrolytes, urate, and creatinine concentrations and 24 hour urinary sodium excretion were monitored every four weeks and serum magnesium concentration and plasma renin activity at the end of the washout and treatment periods. After eight weeks of treatment systolic and diastolic blood pressures were significantly reduced in patients taking 125 and 500 micrograms cyclopenthiazide when compared with those taking placebo. The decrement in serum potassium concentration (0.6 mmol/l) and increase in serum urate concentration 0.06 mmol/l) were greatest with the 500 micrograms dose, the increase in serum urate concentration alone being significant. No change in serum magnesium concentration or 24 hour urinary sodium excretion was noted with any dose of cyclopenthiazide. Only the 500 micrograms dose of cyclopenthiazide significantly increased the mean plasma renin activity (1.8 (95% confidence interval 0.2 to 3.4)-5.4 (3.9 to 6.8) nmol angiotensin I/l/h); the other doses like the placebo had no effect. Cyclopenthiazide 125 micrograms, a dose lower than is currently marketed, produced a similar hypotensive response to 500 micrograms of the drug without upsetting the biochemical profile.     

口腔雾化药物吸入联合小儿双金清热口服液治疗疱疹性口炎的临床疗效

目的:研究口腔雾化药物吸入联合小儿双金清热口服液治疗疱疹性口炎的临床疗效。方法:选择2012年5月至2014年5月在我院接受治疗的疱疹性口炎患者122例实施研究。根据数字法随机分成观察组及对照组各61例,观察组给予口腔雾化药物吸入以及小儿双金清热口服液进行治疗,对照组单纯给予小儿双金清热口服液进行治疗,对比两组治疗后的疗效、相关康复指标以及治疗后的不良反应。结果:观察组的总有效率是98.36%,显著高于对照组的88.52%,差异有统计学意义(P0.05)。观察组的热退时间和疱疹消退时间以及康复时间均分别显著少于对照组,差异均有统计学意义(均P0.05)。观察组治疗后的总不良反应发生率与对照组相比,差异无统计学意义(P0.05)。结论:利用口腔雾化药物吸入联合小儿双金清热口服液对疱疹性口炎患儿进行治疗,效果较好,安全性更高,值得在临床上推广应用。     

利多卡因咽喉表面麻醉对腹腔镜胆囊切除术患者应激反应、血流动力学及恢复质量的影响

摘要 目的：探讨利多卡因咽喉表面麻醉对腹腔镜胆囊切除术（LC）患者应激反应、血流动力学及恢复质量的影响。方法：采用随机数字表法将长沙市第一医院2019年4月-2021年6月期间收治的80例行LC患者分为对照组（40例,接受全身麻醉）和观察组（40例,对照组的基础上接受利多卡因咽喉表面麻醉）。对比两组血流动力学指标、应激反应指标、呛咳和躁动的发生情况、疼痛情况及生活质量。结果：观察组气管插管即刻（T1）~手术结束时（T4）收缩压（SBP）、舒张压（DBP）和心率（HR）低于对照组同期（P<0.05）。观察组术后即刻皮质醇（Cor）、促肾上腺皮质激素（ACTH）低于对照组（P<0.05）。观察组的呛咳发生率、躁动发生率以及总发生率明显低于对照组（P<0.05）。观察组术后6 h、术后12 h、术后24 h疼痛视觉模拟评分法（VAS）评分低于对照组同期（P<0.05）。观察组术后1个月活力、躯体疼痛、社会功能、生理功能、总体健康、精神健康、生理职能、情感职能评分高于对照组（P<0.05）。结论：利多卡因咽喉表面麻醉用于LC患者,可发挥气道保护作用,减轻患者的应激反应,维持患者血流的动力平衡,提高恢复质量。     

Chronic recurrent aphthous stomatitis: oral treatment with low-dose interferon alpha

Recombinant human interferon alfa-2a (HuIFN alpha) was administered orally once daily in a low concentration (1,200 IU/day) to nine patients with chronic recurrent aphthous stomatitis (RAS), and a placebo solution was given to 10 control chronic RAS patients in a double-blind study. All HuIFN alpha-treated patients had total remission of their aphthae within a 2-week period, while placebo control patients had no change in their condition. The 10 placebo control patients were then treated with HuIFN alpha in a manner identical to that used for the initial principal group. Within a 2-week period, all original placebo patients had complete remission of their aphthae. Eleven of the patients did not have a recurrence of RAS during a subsequent 6-month observation period. Eight patients had recurring aphthae; however, the lesions were resolved by retreating with oral HuIFN alpha for less than 1 week.     

抗病毒护肝治疗乙肝合并肺结核患者的疗效研究

目的:研究抗病毒及护肝治疗在肺结核(Tuberculosis,TB)合并乙肝病毒感染(Hepatitis B virus infection,HBVI)患者中的疗效。方法:选择2012年6月至2013年6月本院收治TB合并HBVI患者96例,以数字表法随机分成观察组(50例)及对照组(46例)。对照组患者予以抗病毒、抗结核治疗,观察组基于此方案另予以药物甘利欣。对比两组患者的临床疗效、肝功能指标及炎症反应。结果:观察组患者丙氨酸转氨酶(alanine aminotransferase,ALT)、天门冬氨酸转氨酶(Aspartate aminotransferase,AST)及总胆红素(Total bilirubin,T-Bil)水平在治疗第15天和第30天均显著低于对照组,差异有统计学意义(P<0.05)。观察组患者治疗后血清透明质酸(Hyaluronic acid,HA),IV型胶原(IV Collagen,IV-C)及III型前胶原(Procollagen III,PCIII)较治疗前显著降低,且显著低于对照组(P<0.05)。对照组治疗后血清HA显著降低,其余指标无统计学差异(P>0.05)。观察组疗效显著优于对照组,差异具有统计学意义(P<0.05)。结论:抗病毒及护肝方案对TB合并HBVI患者具有显著的临床疗效,能够缓解肝损害,值得临床推荐。     

Amantadine-HCl (Symmetrel) in the Management of Parkinson's Disease: A Double-Blind Cross-Over Study

A double-blind cross-over study was carried out in 54 patients with Parkinson''s disease to evaluate the efficacy of amantadine hydrochloride as compared to a lactose placebo in the management of this illness. Amantadine proved to be a useful and safe addition to the armamentarium when given in daily doses of 200 mg. Forty-eight per cent of patients experienced moderate to good results while 31% showed no measurable improvement. The quality of the improvement was inferior to that obtained with levodopa, but the side effects were fewer. The study could not demonstrate a useful synergistic action between the two drugs, nor could the response to amantadine be used to predict that with levodopa. On the other hand, the addition of amantadine was useful in a few instances where optimal therapeutic doses of levodopa could not be given because of side effects. The mechanism of action of amantadine is still conjectural, but there is strong evidence to indicate some interaction with central dopamine metabolism.     

四黄散外敷对竹叶青蛇咬伤肿胀的疗效观察

目的 探讨四黄散外敷治疗竹叶青蛇咬伤肿胀的临床疗效.方法 选择2017年10月～2020年4月我院收治的112例竹叶青蛇咬伤肿胀患者为研究对象,采用随机数字表法将患者分为观察组和对照组,每组56例.对照组采用常规蛇咬伤处理方案,包括清创、引流、注射抗蛇毒血清及对症治疗等.观察组在对照组治疗基础上采用四黄散外敷治疗.观察...