Extended-release tolterodine with or without tamsulosin in men with lower urinary tract symptoms and overactive bladder: effects on urinary symptoms assessed by the International Prostate Symptom Score

OBJECTIVE

To evaluate the efficacy of tolterodine extended‐release (ER) plus tamsulosin on lower urinary tract symptoms (LUTS) as assessed by changes in the International Prostate Symptom Score (IPSS) in men who met symptom entry criteria for both overactive bladder (OAB) and benign prostatic hyperplasia (BPH) trials.

PATIENTS AND METHODS

Men aged ≥40 years with an IPSS of ≥12 and diary‐documented OAB symptoms (≥8 voids/24 h and ≥3 urgency episodes/24 h, with or without urgency urinary incontinence) who reported at least moderate problems related to their bladder condition were randomized to receive placebo, tolterodine ER (4 mg), tamsulosin (0.4 mg), or tolterodine ER (4 mg) + tamsulosin (0.4 mg) once daily for 12 weeks. Patients completed the IPSS at baseline and at 1, 6 and 12 weeks.

RESULTS

Patients receiving tolterodine ER + tamsulosin had significantly greater improvements than those taking placebo on IPSS storage subscale scores and scores for all three individual storage items included on the IPSS (urinary frequency, urgency, and nocturnal micturitions) by 12 weeks. Storage subscale and urgency scores were significantly improved vs placebo at 1 and 6 weeks, whereas frequency scores were significantly improved at 6 weeks. Changes in IPSS storage subscale and individual storage item scores in the tolterodine ER and tamsulosin monotherapy groups were not significantly different from placebo at most time points. IPSS voiding subscale scores and scores for three of four individual voiding items (sensation of incomplete emptying, intermittency, and weak stream) were significantly improved by 12 weeks for patients receiving tamsulosin monotherapy vs placebo. Voiding subscale and intermittency scores were significantly improved vs placebo at 1 week; weak stream scores were significantly improved at 1 and 6 weeks. The IPSS voiding subscale and individual voiding item scores in the tolterodine ER + tamsulosin and tolterodine ER groups were not significantly different from placebo at most time points.

CONCLUSIONS

In this distinct clinical research population of men who met traditional symptom entry criteria for both OAB and BPH trials, tolterodine ER + tamsulosin was significantly more effective than placebo in treating storage LUTS, including OAB symptoms. Tamsulosin monotherapy produced significant improvements in voiding LUTS.     

爱普列特治疗良性前列腺增生的有效性及安全性

目的 评价爱普列特治疗BPH的有效性和安全性.方法 采用随机、双盲、双模拟及安慰剂对照的多中心临床试验方法.分3组:爱普列特组10例,平均年龄(72±10)岁;非那雄胺(商品名:保列治)组13例.平均年龄(70±10)岁;安慰剂组16例,平均年龄(70±7)岁.3组患者接受治疗时间均为6个月.每月随访1次,随访评估内容包括IPSS、困扰评分、前列腺体积、尿流率、残余尿量、PSA及国际勃起功能评分问卷(IIEF-5)等,治疗前所有评估指标3组间比较差异均无统计学意义(P值均＞0.05).采用SAS 9.0统计学软件,双侧检验,计量数据组间比较采用t检验,计数数据组间比较采用χ~2检验,a=0.05.结果 爱普列特组IPSS评分F降50.0%±10.3%,与保列治组(37.0%±11.2%)比较差异无统计学意义(P=0.94),但均高于安慰剂组(22.0%±7.6%,P＜0.05);爱普列特组前列腺体积缩小40.0%±12.1%,明显高于保列治组(19.1%±7.3%,P=0.041)及安慰剂组(4.3%±3.2%,P=0.004),保列治组前列腺体积缩小百分比与安慰剂组比较差异无统计学意义(P=0.348).爱普列特组患者Q_(max)改善70.2%±13.9%,与保列治组(50.0%±9.7%)比较差异无统计学意义(P=0.630),但均显著高于安慰剂组(0.5%±0.8%,P＜0.05).其他几项评估指标3组间比较差异无统计学意义.结论 爱普列特能安全有效地治疗BPH,与保列治比较,缩小前列腺体积的疗效更快且更显著.     

Analysis of single items on the Self-Esteem and Relationship questionnaire in men treated with sildenafil citrate for erectile dysfunction: results of two double-blind, placebo-controlled trials

Associate Editor Michael G. Wyllie Editorial Board Ian Eardley, UK Jean Fourcroy, USA Sidney Glina, Brazil Julia Heiman, USA Chris McMahon, Australia Bob Millar, UK Alvaro Morales, Canada Michael Perelman, USA Marcel Waldinger, Netherlands

OBJECTIVE

To evaluate the effect of sildenafil citrate on each item of the 14‐item Self‐Esteem And Relationship (SEAR) questionnaire, which is used to measure self‐esteem, confidence, satisfaction with sexual relationship, and overall relationship satisfaction in men with erectile dysfunction (ED).

PATIENTS AND METHODS

Data were combined from two 12‐week, double‐blind, placebo‐controlled, flexible‐dose sildenafil trials having identical protocols, one conducted in the USA and the other in Mexico, Brazil, Australia and Japan. All men had ED and were aged ≥18 years. Response categories of each SEAR item used a 4‐week reference period and were based on a five‐point scale (1, almost never/never; 2, a few times; 3, sometimes; 4, most times; 5, almost always/always). The difference (sildenafil vs placebo) in the change from baseline to week 12 was evaluated with a Wilcoxon rank sum test using ridit analysis, and an analysis of covariance model that included treatment group, centre, study and baseline item score.

RESULTS

Compared with the 274 patients receiving placebo, the 279 receiving sildenafil reported significantly greater mean and median improvements (P < 0.001) in each of the 14 SEAR items. The probability of increased psychosocial benefit from baseline to week 12 was higher with sildenafil for each SEAR item, and ranged from 0.60 (‘My partner was unhappy with the quality of our sexual relations’[item reverse‐scored]) to 0.72 (‘I was satisfied with my sexual performance’). Across all items, the mean (sd ) probability was 0.67 (0.04) that a randomly selected patient in the sildenafil group would have a more favourable change relative to a randomly selected patient in the placebo group.

CONCLUSIONS

Sildenafil produced substantial and meaningful improvements at the item‐specific level. This analysis complements previously published work on self‐esteem, confidence and relationship satisfaction.     

Information Loss over Time Defines the Memory Defect of Propofol: A Comparative Response with Thiopental and Dexmedetomidine

Background: Sedative-hypnotic drugs impair memory, but details regarding the nature of this effect are unknown. The influences of propofol, thiopental, and dexmedetomidine on the performance of a task that isolates specific components of episodic memory function were measured.

Methods: Working (1 intervening item, 6 s) and long-term memory (10 intervening items, 33 s) were tested using auditory words in a continuous recognition task before and during drug administration. Eighty-three volunteer participants were randomly assigned to receive a constant target concentration of drug or placebo, producing sedative effects from imperceptible to unresponsiveness. Responsive participants were categorized as high or low performers, using a median split of long-term memory performance during drug administration. Recognition of words at the end of the study day was assessed.

Results: High performers had acquisition of material into long-term memory when drug was present at the same level as placebo. Retention of this material at 225 min was significantly less for propofol (39 +/- 23% loss of material) than for other drugs (17-23% loss; P < 0.01). Greater sedation in low performers was evident in multiple measures. Memory for words presented before drug was no different from that associated with placebo for all groups.     

Botulinum Toxin Type A Treatment of Multiple Upper Facial Sites: Patient-Reported Outcomes

BACKGROUND Aesthetic treatment planning must address subjects' goals and include subject-reported outcomes.
OBJECTIVE The objective was to compare the effect of botulinum neurotoxin type A (BoNTA) with placebo on subject-reported outcomes and to assess the utility of 64 U of BoNTA to treat the entire upper face.
METHODS Forty female subjects were randomized to receive 64 U of BoNTA or identical placebo injections (double-masked) divided among 16 sites of the upper face and were followed for 12 weeks. Subjects unimproved at Week 4 were eligible for open-label BoNTA treatment and were followed through Week 16. Main outcome measures were scores on seven items of the Facial Line Outcomes Questionnaire (FLO-7) and results on the Self-Perception of Age (SPA) for assessing age of appearance relative to actual age.
RESULTS BoNTA treatment resulted in significant improvements on the FLO-7 scores that were maintained throughout the study. BoNTA treatment also reduced age of appearance in a majority of subjects. Placebo had no effects on any measure. No serious adverse events occurred.
CONCLUSION Sixty-four-unit BoNTA treatment of upper facial rhytids safely and significantly improves subject-reported outcomes, as measured by the FLO-7 and SPA, and results in a younger, more satisfying, relaxed appearance.     

Information loss over time defines the memory defect of propofol: a comparative response with thiopental and dexmedetomidine

BACKGROUND: Sedative-hypnotic drugs impair memory, but details regarding the nature of this effect are unknown. The influences of propofol, thiopental, and dexmedetomidine on the performance of a task that isolates specific components of episodic memory function were measured. METHODS: Working (1 intervening item, 6 s) and long-term memory (10 intervening items, 33 s) were tested using auditory words in a continuous recognition task before and during drug administration. Eighty-three volunteer participants were randomly assigned to receive a constant target concentration of drug or placebo, producing sedative effects from imperceptible to unresponsiveness. Responsive participants were categorized as high or low performers, using a median split of long-term memory performance during drug administration. Recognition of words at the end of the study day was assessed. RESULTS: High performers had acquisition of material into long-term memory when drug was present at the same level as placebo. Retention of this material at 225 min was significantly less for propofol (39 +/- 23% loss of material) than for other drugs (17-23% loss; P < 0.01). Greater sedation in low performers was evident in multiple measures. Memory for words presented before drug was no different from that associated with placebo for all groups. CONCLUSIONS: Lack of retention of material acquired into long-term memory during propofol administration, associated with minimal sedation, seems to define drug-induced amnesia. Sedation seems to impair the acquisition or encoding of material into long-term memory. Therefore, the putative targets of drug-induced amnesia by propofol are processes associated with retention of material in long-term memory.     

A new measure of placebo response and patient satisfaction in office encounters.

OBJECTIVES: Placebo response is defined as a change in health status resulting from the symbolic significance attributed by the patient or proxy to the physician encounter. Our goals were to validate the PR12 survey as a measure of placebo response and to analyze the placebo response as a discrete and measurable component of everyday office encounters with the otolaryngologist. STUDY DESIGN: This was a prospective, before-and-after clinical outcomes study of 95 children aged 6 months to 12 years conducted in an academic metropolitan pediatric otolaryngology practice. Caregivers completed the PR-12 survey at entry and at least 4 weeks later. The survey included 3 domains (4 questions each) reflecting the main components of the placebo response: meaningful explanation, care and concern, and mastery and control. PR-12 was correlated with longitudinal change in health status at least 1 to 2 months after the baseline visit. Outcome measures included direct and indirect measures of change in disease-specific quality of life and satisfaction with change. RESULTS: Test-retest reliability was fair for most PR-12 survey items (R = 0.41 to 0.76) but was higher for domains (0.60 to 0.66) and the overall survey score (0.66). PR-12 had excellent internal consistency (Cronbach's alpha 0.91) and appropriate construct validity. Caregiver satisfaction change at follow-up correlated with the PR-12 (r = -.25, P = 0.036). Conversely, no correlation was seen between the PR-12 and direct and indirect measures of change in disease specific quality of life. CONCLUSION: Placebo response is an important and potentially measurable aspect of clinical encounters. PR-12 is a promising first step at creating a brief, reliable, and valid instrument to assess the placebo response. SIGNIFICANCE: Reemphasizing the therapeutic potential of the doctor-patient relationship may improve quality of care and disease outcomes.     

Safety and Efficacy of Sildenafil Citrate for the Treatment of Female Sexual Arousal Disorder: A Double-Blind,Placebo Controlled Study

PurposeWe evaluated the efficacy and safety of sildenafil citrate in spontaneously or surgically postmenopausal women with female sexual arousal disorder (FSAD).Materials and MethodsSildenafil (a 50 mg dose adjustable to 100 or 25 mg) was evaluated in a 12-week, double-blind, placebo controlled study in 202 postmenopausal women with FSAD who had protocol specified estradiol and free testosterone concentrations, and/or were receiving estrogen and/or androgen replacement therapy. Patients were excluded if emotional, relationship or historical abuse issues contributed significantly to sexual dysfunction. Primary end points were questions 2 (increased genital sensation during intercourse or stimulation) and 4 (increased satisfaction with intercourse and/or foreplay) from the Female Intervention Efficacy Index (FIEI). Secondary end points were the remaining questions from this index, the Sexual Function Questionnaire and sexual activity event log questions.ResultsSignificant improvements in FIEI questions 2 (p = 0.017) and 4 (p = 0.015) were noted with sildenafil compared with placebo. For women with FSAD without concomitant hypoactive sexual desire disorder (HSDD) sildenafil was associated with significantly greater improvement in 5 of 6 FIEI items compared with placebo (p <0.02). No significant improvements were shown for women with concomitant HSDD. Most adverse events were mild to moderate with headache, flushing, rhinitis, nausea and visual symptoms reported most frequently.ConclusionsSildenafil was effective and well tolerated in postmenopausal women with FSAD without concomitant HSDD or contributory emotional, relationship or historical abuse issues. All patients had protocol specified estradiol and free testosterone concentrations or were receiving estrogen and/or androgen replacement therapy.     

Patient-reported Outcomes in Chinese Subjects Treated with OnabotulinumtoxinA for Crow’s Feet Lines

BackgroundCrow’s feet lines (CFLs) can impact the emotional state, self-perception, and consciousness regarding appearance of patients.ObjectiveThis study sought to assess patient-reported outcomes after onabotulinumtoxinA treatment for CFLs among Chinese subjects.MethodsA five-month, double-blind, randomized, parallel-group, placebo-controlled Phase III clinical study was conducted including Chinese adults with moderate-to-severe CFLs at maximum smile. Subjects were randomized 3:1 to 24 U of onabotulinumtoxinA or placebo and completed the 11-item Facial Line Outcomes (FLO-11) questionnaire and Facial Line Satisfaction Questionnaire (FLSQ) at baseline; on Days 8, 15, and 30; and monthly thereafter until Day 150. Item-level and/or domain analyses for the FLO-11 and FLSQ were conducted.ResultsOf 417 treated subjects, 316 received onabotulinumtoxinA and 101 received placebo. For all 10 validated stand-alone FLO-11 items, there was a significantly greater proportion of responders in the onabotulinumtoxinA group versus placebo (P<0.001) at Day 30 that was maintained through Day 150. Significant improvements at Day 30 were reported for all FLSQ items and the FLSQ Follow-up Impact Domain (P≤0.01).ConclusionFLO-11 and FLSQ data indicated high satisfaction and significant improvements in appearance-related and emotional impacts through Day 150 in patients treated with onabotulinumtoxinA for moderate-to-severe CFLs in Chinese subjects.Trial RegistrationClinicalTrials.gov identifier no. {"type":"clinical-trial","attrs":{"text":"NCT02195687","term_id":"NCT02195687"}}NCT02195687     

Vardenafil improves urodynamic parameters in men with spinal cord injury: results from a single dose, pilot study

PURPOSE: We assessed urodynamic changes after vardenafil administration in spinal cord injured male patients on oxybutynin treatment. MATERIALS AND METHODS: We performed a single center, randomized, double-blind, placebo controlled trial in 25 patients with spinal cord injury who had erectile dysfunction and micturition disorders. A baseline urodynamic test was performed as well as a second urodynamic test 1 to 3 hours after the administration of 20 mg vardenafil and placebo in 15 and 10 cases, respectively. In all patients standard oral oxybutynin administration was not discontinued. Statistical assessment included the 3 urodynamic parameters maximum detrusor pressure during voiding, maximum cystometric capacity and detrusor overactivity volume. RESULTS: Placebo administration did not affect urodynamic parameters. After vardenafil administration maximum detrusor pressure was significantly decreased (59.3 vs 52.1 cm H(2)O, p <0.001) and maximum cystometric capacity considerably improved (233.5 vs 272 ml, p <0.001). The most dramatic variations were observed for detrusor overactivity volume (174 vs 218 ml, p <0.0001). In 7 patients with American Spinal Injury Association classification A and spinal cord injury above T6 we observed the most significant improvement in the evaluated urodynamic items, including maximum detrusor pressure 57 vs 52 cm H(2)O (p = 0.039), maximum cystometric capacity 253 vs 296 ml (p = 0.004) and detrusor overactivity volume 177 vs 229 ml (p = 0.003). CONCLUSIONS: This trial demonstrates that in spinal cord injured patients a single 20 mg vardenafil administration achieved a significant decrease in maximum detrusor pressure, an improvement in maximum cystometric capacity and a remarkable increase in detrusor overactivity volume value.     

万艾可治疗勃起功能障碍的疗效和安全性

目的 :评估万艾可 (Viagra○R)治疗男性勃起功能障碍 (ED)的有效性和安全性。　方法 :本试验为双盲、随机(安慰剂 :西地那非 ,1:3)、安慰剂对照、剂量可调整 (2 5、5 0和 10 0mg)、持续 12周的临床研究。共有 84名受试者参与本研究。　结果 :对主要疗效指标 (IIEF问题 3、4)的分析结果显示 ,万艾可对ED病人达到和维持勃起能力的改善作用显著优于安慰剂 (P <0 .0 0 0 1) ,万艾可的临床总有效率为 86 % ,显著高于安慰剂 (37% ) ;对心理性、器质性和混合性ED的有效率分别为 83%、79%和 81% (安慰剂组分别为 5 0 %、33%和 30 % )。同时 ,对次要疗效指标评估 (IIEF其余 13个问题、记事表和总评题 )亦显示 ,万艾可改善性生活的作用明显优于安慰剂 ;万艾可组性交成功率平均为71.8% ,显著高于安慰剂组 (17.0 % ) ;有 87.3%的万艾可组受试者认为研究药物改善了其勃起功能 ,显著高于安慰剂组 (36 .8% )。无 1名受试者因不良事件而中断研究 ,万艾可组的不良事件发生率 (33.3% )较安慰剂组高(19.0 % ) ,但绝大多数为轻度、一过性的。　结论 :口服万艾可是一种可治疗各种病因导致的勃起功能障碍安全有效的药物 ,按需服用时能很好耐受。     

A double-blind placebo-controlled study evaluating the onset of action of doxazosin gastrointestinal therapeutic system in the treatment of benign prostatic hyperplasia

OBJECTIVE: To determine the onset of improvement in benign prostatic hyperplasia symptoms in patients after treatment with doxazosin gastrointestinal therapeutic system (DOX GITS) versus placebo. METHODS: In this prospective, randomized, double-blind, placebo-controlled trial, baseline values, including International Prostate Symptom Score (IPSS) and maximum urine flow rate (Q(max)), were determined following a 2-week placebo run-in. Patients received DOX GITS 4 mg/d (n = 108) or placebo (n = 105) for 14 days. IPSS was measured on Days 3, 7, and 14; Q(max) on Days 1, 3, 7, and 14; and the patients' perception of improvement was measured on Days 1 and 2 in the evening at home and in the office on Day 14. RESULTS: Significantly more patients treated with DOX GITS than placebo perceived improvement after Day 1 (60.6% vs. 41.9%) through Day 14 (84.3% vs. 64.1%). On Day 1, improvement in Q(max) with DOX GITS was not significantly different compared with placebo. On Day 3 of the trial (1) IPSS improvement was significantly greater with DOX GITS than with placebo; (2) proportion of patients with > or =30% improvement in IPSS was significantly greater with DOX GITS (49.5%) than placebo (28.4%) and remained so through Day 14; (3) improvement in Q(max) was significantly greater with DOX GITS (3.7 mL/s) than placebo (1.9 mL/s) and remained so through Day 14; (4) proportion of patients with > or =3 mL/s increase in Q(max) was statistically greater with DOX GITS (54.4%) versus placebo (30.8%) and remained so through Day 14. CONCLUSIONS: DOX GITS significantly improved IPSS and Q(max) by Day 3 of treatment, and these changes were maintained through Day 14. More patients receiving DOX GITS than placebo perceived improvement in symptoms as early as Day 1.     

The efficacy and safety of tadalafil in United States and Puerto Rican men with erectile dysfunction

PURPOSE: We evaluate the efficacy and safety of tadalafil, taken as needed, in men with mild to severe erectile dysfunction (ED) and assess sexual intercourse attempt patterns. MATERIALS AND METHODS: In this multicenter, double-blind, placebo controlled, parallel study conducted in the United States and Puerto Rico 207 men with ED were randomized to placebo or 20 mg tadalafil for 12 weeks. The primary efficacy variables were changes from baseline in the mean International Index of Erectile Function erectile function domain score and mean per patient percentage of "yes" responses to Sexual Encounter Profile (SEP) diary questions 2 (successful penetration) and 3 (successful intercourse). The Global Assessment Question was a secondary end point and post hoc analyses on sexual intercourse attempt patterns were conducted. RESULTS: Men treated with tadalafil compared with placebo reported greater mean changes from baseline on the erectile function domain score (9.3 vs 0.3 with placebo, p <0.001) and on the mean per patient percentage of successful penetration (SEP question 2, 31.6% vs 2.3% with placebo, p <0.001) and successful intercourse attempts (SEP question 3, 43.6% vs 3.5% with placebo, p <0.001). The per treatment group percentage of successful intercourse attempts during treatment was higher for tadalafil than placebo (67.6% vs 24.1%, respectively, p <0.001) and most successful intercourse attempts occurred between 4 and 36 hours after taking tadalafil. Of the men treated with tadalafil 82.8% reported improved erections versus 19.6% taking placebo (Global Assessment Question, p <0.001). The most common treatment emergent adverse events were headache (15.7% vs 6.3% with placebo), back pain (8.8% vs 0%), and dyspepsia (7.5% vs 0%). CONCLUSIONS: Tadalafil (20 mg) significantly improved erectile function and patients did not closely temporally link sexual intercourse attempts with taking tadalafil. Tadalafil was also well tolerated in both groups of men with mild to severe ED.     

Protein and energy metabolism with biosynthetic human growth hormone after gastrointestinal surgery.

The effect of biosynthetic human growth hormone (BSHGH) on postoperative protein and energy metabolism has been studied in patients who had major gastrointestinal surgery. Seven patients received placebo and seven patients received BSHGH, 0.1 mg/kg/24 h, for the first six postoperative days. Mean total nitrogen excretion was significantly lower with BSHGH (31.5 +/- 2.4 g N) (2287 +/- 160 mmol) than with placebo (42.7 +/- 3.1 g N) (3049 +/- 219 mmol) over the 6-day study period. The mean daily measured energy expenditure over days 3-6 was higher with BSHGH (31.3 +/- 1.8 kcal/kg LBM/24 h) (131 +/- 7 kJ/kg LBM/24 h) than with placebo (27.6 +/- 0.8 kcal/kg LBM/24 h) (114 +/- 2 kJ/kg LBM/24 h). Fat oxidation with BSHGH (2.05 +/- 0.26 mg/kg LBM/24 h) was greater than with placebo (1.5 +/- 0.17 mg/kg LBM/24 h) and protein oxidation was less with BSHGH (0.68 +/- 0.07 g/kg LBM/24 h) than with placebo (0.9 +/- 0.09 g/kg LBM/24 h) on days 1-6. Postoperative nitrogen turnover (BSHGH 943 +/- 174 mg N/kg LBM/24 h, placebo 557 +/- 50 mg N/kg LBM/24 h) (BSHGH 67 +/- 13 mmol/kg LBM/24 h, placebo 40 +/- 4 mmol/kg LBM/24 h), protein synthesis (BSHGH 5.31 +/- 1.09 g prot/kg LBM/24 h, placebo 2.54 +/- 0.33 g prot/kg LBM/24 h) and protein breakdown (BSHGH 5.90 +/- 1.09 g prot/kg LBM/24 h, placebo 3.48 +/- 0.31 g prot/kg LBM/24 h) were greater with BSHGH. On the first postoperative day serum insulin and blood glucose levels were higher with BSHGH than with placebo, and on days 4 and 7 serum somatomedin-C levels were significantly elevated. This study shows that BSHGH alters postoperative protein and energy metabolism by reducing protein oxidation and increasing fat oxidation with raised rates of whole body nitrogen turnover.     

Transdermal nitroglycerin in angina pectoris

Stress is sometimes involved in cardiac patients when a number of different drugs are necessary for treatment that are taken in a variety of dose regimes. Any new method for drug delivery that can relieve some of this stress is therefore of interest. Such a preparation is glyceryl trinitrate (GTN) in the form of a skin patch (Transiderm-Nitro) and this was compared to placebo in a double-blind cross-over trial. Following a one-week control period, patients were randomly allocated to three weeks treatment with placebo followed by three weeks with Transiderm-Nitro (1–15 mg in 24 h) or vice versa. Analysis was performed on 77 cases, 37 in the placebo first group (group A) and 40 in the Transiderm-Nitro first group (group B). Irrespective of treatment order, mean weekly anginal attack rates and GTN requirements were significantly less on the active patch than on placebo. Thus, there was a 21 per cent reduction in anginal attacks on placebo but 53 per cent reduction on Transiderm-Nitro (p<O.OOl); while the mean GTN requirement was reduced by 29 per cent on placebo but 56 per cent on Transiderm-Nitro (p<O.OOl). There were no significant changes in pulse rate or recumbent or upright blood pressure. Patients' preferences (blind) were in favour of Transiderm-Nitro (p<O.OOl). The most frequent side-effect was headache, which occurred in 22 per cent of patient; on Transiderm-Nitro but in only 3 per cent on placebo (p<O.Ol). Skin rashes occurred in 5 per cent on Transiderm-Nitro and 4 per cent on placebo (NS). This short-term trial demonstrated highly significant effects from the transdermal GTN preparation in comparison to placebo.     

Clinical efficacy and tolerability of extended-release tolterodine and immediate-release oxybutynin in Japanese and Korean patients with an overactive bladder: a randomized, placebo-controlled trial

OBJECTIVE: To compare extended-release (ER) tolterodine and immediate-release (IR) oxybutynin with placebo in Japanese and Korean patients with an overactive bladder (OAB). PATIENTS AND METHODS: Men and women aged >or= 20 years with symptoms of urinary urgency, urinary frequency (>or= 8 micturitions/24 h), urge incontinence (>or= 5 episodes/week) and symptoms of OAB for >or= 6 months were randomized to double-blind treatment with tolterodine ER 4 mg once daily, oxybutynin IR 3 mg three times daily or placebo for 12 weeks. Efficacy assessments included changes from baseline in numbers of incontinence episodes per week, voids/24 h and mean volume voided/void. Patient perceptions of bladder condition, urgency and treatment benefit were also assessed. RESULTS: In all, 608 patients were randomized to treatment with tolterodine (240), oxybutynin (246) or placebo (122). More patients prematurely withdrew on oxybutynin (23%) than with tolterodine (10.4%) or placebo (16.4%). After 12 weeks of treatment, the median number of incontinence episodes/week was reduced significantly more in the tolterodine (79%; P= 0.0027) and oxybutynin groups (76.5%; P= 0.0168) than on placebo (46.4%). There were also significantly greater improvements in the number of voids/24 h and volume voided/void with tolterodine and oxybutynin than with placebo. More patients in the tolterodine and oxybutynin than in the placebo groups reported improvements in perceived bladder condition, ability to hold urine and treatment benefit. Patients treated with oxybutynin reported more adverse events than those treated with tolterodine or placebo. Dry mouth was significantly more common with oxybutynin than with tolterodine (53.7% vs. 33.5%; P < 0.001), and occurred in 9.8% of placebo patients. CONCLUSION: Tolterodine ER has similar efficacy but is better tolerated than oxybutynin IR in Japanese and Korean patients with OAB.     

Etoricoxib provides analgesic efficacy to patients after knee or hip replacement surgery: a randomized, double-blind, placebo-controlled study

In this randomized, double-blind, placebo-controlled, multicenter study we assessed the analgesic effect of etoricoxib (a new cyclooxygenase-2 inhibitor) in patients having had knee or hip replacement surgery. A total of 228 patients with moderate or severe pain were randomly allocated within 72 h after surgery to receive etoricoxib 120 mg, controlled-release naproxen sodium 1100 mg, or placebo (1:1:1) on day 1 followed by etoricoxib and placebo (1:2) on days 2 to 7. Patients reported pain scores, rescue (opioid-combination) medication use, and the response to study drug. On day 1, etoricoxib provided an analgesic effect superior to placebo and similar to controlled-release naproxen sodium as demonstrated by the total pain relief score over 8 h, the primary end-point; least-squares mean scores were 11.0, 11.5, and 5.6, respectively (P < 0.001 versus placebo). Similarly, a larger percentage of patients receiving etoricoxib and naproxen sodium than those receiving placebo reported good to excellent responses to study drug: 53%, 60%, and 26% respectively. On days 2-7, etoricoxib demonstrated a significant reduction of rescue medication use, 35% (P < 0.001 versus placebo). The clinical relevance of the decrease was confirmed by Patient's Global Evaluation (P < 0.05 versus placebo). Patients receiving etoricoxib also experienced significantly less "worst" and "average" pain than did those on placebo. Etoricoxib was generally well tolerated in this study; the incidence of adverse experiences was infrequent and similar across treatment groups. In summary, etoricoxib provided analgesia that was similar to controlled-release naproxen sodium on day 1 and superior to placebo with reduced supplemental opioid use over 7 days. IMPLICATIONS: In a postsurgery setting (knee and hip replacements), etoricoxib 120 mg provided analgesia superior to placebo and similar to controlled-release naproxen sodium 1100 mg. Patients receiving etoricoxib suffered less pain and took less opioid rescue medication compared with patients on placebo.     

Initial results of the reliability and validity of a German-language scale for the quantitative measurement of postoperative pain in young children

In a previous study it was proved impossible to evaluate the validity of a system modified according to McGrath et al. for measuring postoperative pain in children. Three reasons were postulated for this result. The analgesics used did not modulate the pain in such a manner that the statistical analysis was effective; or the postoperative pain had an acute onset or fluctuated and the regular observations did not allow detection of the pain peaks; or the system used did not measure pain. Therefore, a new and different approach was adopted to evaluate the reliability and validity of a scoring system for the measurement of postoperative pain in small children. MATERIAL. Sixty children classed as ASA I and II and aged between 1 and 5 years were randomly allocated to 2 groups: one group received Tramadol (0.5 mg/kg) after the induction of anesthesia and the other group received placebo. Premedication and anesthesia were standardized. All indications were accepted except for urgent operations and painful diseases. For 1 h after the operation the children were continuously observed by an experienced pediatric anesthetist who did not know what drugs had been given. Every 15 min and when the observer was convinced that the children were in pain and needed analgesics the following items were scaled: wakefulness, wake-up reaction, crying, facial expression, position of the trunk, position of the legs, muscle tone, making contact, verbal communication on being asked about pain, special defense against stimuli and consolability. The items were included in a factor analysis (principal components). The number of the factors was detected using the Scree test. The only items accepted as reliable were those that had a substantial load of at least 0.4 at each measurement. The reliability coefficient was computed with the split-half technique (odd-even). The validity was estimated with a multifactorial analysis of variance with repeated measurements. When the observer was convinced that any child was in pain, Metamizol (15 mg/kg) was administered. Significance was assumed at P less than 0.05. The study was accepted by the ethical committee of the Ruhr University, Bochum. RESULTS. A replication verified the results of the previous study: the factor analysis resulted in a one-factorial solution. Of the 8 items (wakefulness, wake-up reactions, crying, position of the trunk, position of the legs, verbal communications on being asked about pain, special defense against stimuli) only 4 had a sufficiently substantial load on all measurements (crying, facial expression, position of the trunk and position of the legs). (ABSTRACT TRUNCATED AT 400 WORDS)     

Peripheral Analgesic Effects of Ketamine in Acute Inflammatory Pain

Background: This study examined the analgesic effect of local ketamine infiltration, compared with placebo and systemic ketamine, in a human model of inflammatory pain.

Methods: Inflammatory pain was induced by a burn (at 47 [degree sign]C for 7 min; wound size, 2.5 x 5 cm) on the calf in 15 volunteers on 3 separate days with 7-day intervals. They received either (1) subcutaneous infiltration with ketamine in the burn area (local treatment) and contralateral placebo injections, or (2) subcutaneous ketamine contralateral to the burn (systemic treatment) and placebo in the burn area, or (3) placebo on both sides. The study was double-blinded and the order of the treatments was randomized. Hyperalgesia to mechanical and heat stimuli was examined by von Frey hairs and contact thermodes (3.75 and 12.5 cm2), and pain was rated using a visual analog scale (0-100).

Results: The burns produced significant hyperalgesia. Local ketamine infiltration reduced pain during the burn injury compared with systemic treatment and placebo (P 相似文献   

Intravenous acetaminophen (paracetamol): comparable analgesic efficacy, but better local safety than its prodrug, propacetamol, for postoperative pain after third molar surgery

We compared an acetaminophen (paracetamol) 1 g (n = 51) formulation for infusion with propacetamol 2 g (n = 51) and placebo (n = 50) in a randomized, controlled, double-blind, parallel group trial in patients with moderate-to-severe pain after third molar surgery. Treatment efficacy was assessed in house for 6 h after starting the 15-min infusion. Significant effects versus placebo (P < 0.01) were obtained with both active treatments on pain relief, pain intensity difference on a 100-mm visual analog scale, and on a categorical scale (except for propacetamol at 6 h). No significant differences were noted between active groups except at 1 h. Six-hour weighted sums of primary assessments showed significantly better efficacy than placebo (P < 0.0001) and no difference between active treatments. Median stopwatch time to onset of pain relief for active treatment was 6-8 min after infusion start. Active treatments showed comparable efficacy with a significantly longer duration of analgesia and better patients' global evaluation compared with placebo. The incidence of patients reporting local pain at the infusion site was significantly less frequent after IV acetaminophen or placebo (0%) in comparison with propacetamol (49%). In conclusion, acetaminophen 1 g and propacetamol 2 g were superior to placebo regarding analgesic efficacy, with a more frequent incidence of local pain at the infusion site for propacetamol.