A comparison of danazol and placebo in the treatment of adult idiopathic gynaecomastia: results of a prospective study in 55 patients.

In an attempt to define the efficacy of danazol in the treatment of idiopathic gynaecomastia, 55 patients were enrolled into a randomised double-blind comparison of danazol 200 mg twice daily for 3 months against placebo. The results of 52 patients were evaluated, three patients being excluded because of protocol violations. Danazol improved breast tenderness to a significantly greater degree than did placebo (P = 0.022, danazol vs placebo) and was associated with statistically significant improvement in the degree of gynaecomastia and in its measured size (P less than 0.05). The intended management of patients who had received danazol was less likely to be surgery compared to the placebo group when assessed at the end of treatment (27% vs 50%). Minor side effects were common in both groups, but significant weight gain was noted in the danazol group alone. If there is no urgent need for rapid resolution of gynaecomastia, danazol 200 mg twice daily can provide effective control of symptoms and may obviate the need for surgery.     

A double-blind trial on the effect of bunazosin hydrochloride for the symptoms of benign prostatic hypertrophy]

A multicenter clinical trial was carried out on 372 patients in double-blind conditions in order to determine the clinical effects of Ea-0643 (bunazosin hydrochloride) on voiding disorders in benign prostatic hypertrophy, compared with paraprost and placebo. Of the 372 patients, 129 were assigned to bunazosin hydrochloride, 118 to paraprost and 125 to placebo. The improvement rating for all five subjective symptoms improved with passage of time in all the bunazosin hydrochloride, paraprost and placebo groups. A higher improvement rating was obtained in the bunazosin hydrochloride group for retarded urination, urinary stream condition and abdominal pressure at voiding, while the improvement rating was higher for prolonged urination in the placebo group and for residual urine in the paraprost group, but there was no significant difference in improvement ratings between the groups. The daily frequency of voiding decreased to a significant extent in the bunazosin hydrochloride and placebo group at week 1, and there was a significant difference between the bunazosin hydrochloride and the paraprost groups and between the placebo and the paraprost groups. The improvement rating for conditions of voiding was higher with the bunazosin hydrochloride group, when "slightly or better improved" cases were taken into account, but there was no difference between the groups. As for objective symptoms, maximum and average flow rate, useful measures for clinical evaluation of drug effects on voiding disorders, were significantly increased, with a decrease to match in residual urine ratio in the bunazosin hydrochloride group. In terms of maximum and average flow rate bunazosin hydrochloride was significantly superior to paraprost at weeks 1 and 2 and superior to placebo at weeks 2 and 4 and at the final evaluation as well. In terms of residual urine ratio bunazosin hydrochloride was superior to both paraprost and placebo. The global improvement rating, as assessed by the U- and chi 2-tests, was significantly higher in the bunazosin hydrochloride group than in the paraprost group, and there was a significant difference in global improvement ratings, as assessed by the chi 2-test, between the placebo and the paraprost groups, when "moderately or better improved" cases were taken into account. The stratified analysis of the prostate glands, subjective symptoms, maximum flow rate and residual urine ratio revealed that in patients with more advanced conditions the bunazosin hydrochloride group showed significantly superior improvement rates than the paraprost and placebo groups.(ABSTRACT TRUNCATED AT 400 WORDS)     

Serotonin precursors in chronic primary headache. A double-blind cross-over study with L-5-hydroxytryptophan vs. placebo

Serotonin (5-HT) plays a crucial role in mediating the descending pain inhibitory systems and in the pathophysiology of migraine. Previous studies regarding the use of 5-Hydroxytryptophan (5-HTP), the active precursor of 5-HT, in the treatment of Chronic Primary Headache (CPH) have been inconclusive so far. In order to assess the efficacy of the serotonin active precursor in chronic headache prophylaxis, a double-blind cross-over study has been carried out in 31 patients with CPH, comparing L-5-HTP to placebo. Clinical syndromes included: (a) migraine (16 patients); (b) mixed headache (6 patients); (c) psychogenic headache (5 patients); (d) muscle contraction headache (4 patients). L-5-HTP was administered for two months at daily doses of 400 mg p.o. The reduction in severity and frequency of headache in patients taking the active drug and placebo was noted. Mood patterns were also taken into consideration. L-5-HTP proved to be more effective than placebo in reducing both headache frequency and severity, but the difference was not statistically significant. Favourable responses (greater than 50% average reduction in headache symptoms) were obtained in 48% of the cases after the second month of treatment. No significant difference in therapeutic response was observed as related to different clinical syndromes, except for psychogenic headache patients, who responded poorly to the active drug. Side effects, experienced in 19% of the cases, were generally mild and transient. We conclude that L-5-HTP is a medication of moderate efficacy and remarkable safety, providing us with another alternative approach to CPH prophylaxis.     

Extracorporal shock wave therapy in the treatment of Peyronie's disease. First results of a case-controlled approach

OBJECTIVE: To test whether extracorporal shock wave therapy (ESWT) has an effect in the treatment of Peyronie's disease. METHODS: 22 patients with Peyronie's disease and previous unsuccessful oral drug therapy were treated with ESWT in a prospective design with a follow-up of at least 3 months; 23 age-matched patients without previous therapy received oral placebo drug for 6 months daily as control. The standard follow-up included palpation, ultrasound, autophotography and evaluation of symptomatology based on a symptom score. The shock waves were applied under ultrasound guidance using the 'Storz Minilith SL1' lithotripter. RESULTS: The results show a significant decrease in penile curvature in the patients treated with ESWT. Concerning the decrease in pain, subjective improvement and improvement in the quality of sexual intercourse, there was no significant difference to the case-control group. The inhomogeneity of the 2 groups may influence these results due to the questionable varying natural history. CONCLUSIONS: A prospective, controlled multicenter study with standardized parameters (concerning technique and patients) is urgently required to test the effect of ESWT.     

雷洛昔芬对绝经后妇女同型半胱氨酸及血脂的影响

目的观察雷洛昔芬(RLX)对绝经后妇女同型半胱氨酸及血脂的影响。方法采用随机、双盲、安慰剂对照研究,对62例绝经后妇女分为试验组(n=32)和安慰剂组(n=30),分别给予RLX 60 mg/d及安慰剂,共12个月。结果RLX组用药6个月前后同型半胱氨酸无明显变化,用药12个月时明显降低,与安慰剂组比较有显著性差异(P<0.05);RLX组用药12个月总胆固醇、低密度脂蛋白胆固醇显著降低(P<0.01),高密度脂蛋白胆固醇和甘油三酯则无明显变化。结论RLX可降低绝经后妇女同型半胱氨酸水平,降低血清总胆固醇、低密度脂蛋白胆固醇水平。     

盐酸坦索罗辛治疗伴有下尿路症状的BPH有效性和安全性研究

目的 评价长期服用盐酸坦索罗辛治疗伴有下尿路症状(LUTS)的BPH的有效性和安全性.方法 2005-2007年LUTS/BPH患者113例,经4周安慰剂导入期,进入60周开放性研究,每天早餐前口服盐酸坦索罗辛0.2 mg.Ⅰ期治疗(0～12周)结束时对盐酸坦索罗辛的有效性和安全性进行评价,IPSS改善≥25%者行Ⅱ期(13～60周)治疗;IPSS改善＜25%者Ⅱ期联合使用非那雄胺治疗.Ⅱ期治疗结束时行有效性和安全性评价.受试者随访期间监测症状、体征、实验室检查和不良事件.IPSS和Qmax为主要有效性评价参数.结果 113例患者完成Ⅰ期治疗111例,IPSS由治疗前19.5降为15.4,平均改善率21.2%;平均Qmax由治疗前11.2 ml/s提高1.7 ml/s,平均改善率16.5%,治疗前后比较差异均有统计学意义(P＜0.05).完成Ⅱ期治疗95例,其中联合使用非那雄胺25例、未联合使用非那雄胺者70例(P＞0.05),IPSS由治疗前19.0±4.7降为12.6±3.2,改善率30.3%; Qmax由治疗前(11.6±2.3)ml/s提高3.0 ml/s;生活质量评分(QOL)由4.3±0.8降为2.6±0.7,治疗前后比较差异均有统计学意义(P＜0.05).治疗前后IIEF-5评分、前列腺体积和血压差异无统计学意义(P＞0.05).治疗期间共发生13例24次不良事件,其中头晕5例8次、腹泻2例2次、乏力2例5次、口干1例6次,头痛、恶心及皮肤瘙痒各1例1次.无严重不良事件.结果 盐酸坦索罗辛治疗伴有LUTS的BPH患者安全有效,疗效持久,耐受性好,可以作为有效的常规治疗药物.     

Efficacy of trospium chloride in patients with detrusor instability: a placebo-controlled, randomized, double-blind, multicentre clinical trial

OBJECTIVES: To assess the efficacy and safety of trospium chloride (TCl, 20 mg twice daily) in the treatment of detrusor instability, compared with placebo. PATIENTS AND METHODS: In all, 208 patients were allocated at random to either TCl or placebo in a double-blind clinical study; the patients were treated for 3 weeks. Urodynamic values were measured at the beginning and end of the treatment period. Adverse events were recorded on patient diary cards. A confirmatory adaptive procedure with one planned interim analysis was used to evaluate efficacy. RESULTS: Trospium chloride produced significant improvements in maximum cystometric bladder capacity (median treatment effect 22.0 mL, mean 37.3 mL, one-sided P = 0. 0054) and urinary volume at first unstable contraction (median treatment effect 45.0 mL, mean 63.6 mL, one-sided P = 0.0015). The patients' assessment of efficacy showed significantly greater clinical improvement in the TCl group than in the placebo group (two-sided P = 0.0047). Furthermore, TCl was well tolerated, with similar frequencies of adverse events reported in both groups (68% in the TCl and 62% in the placebo group). CONCLUSION: Trospium chloride (20 mg twice daily) is an effective and safe option for the treatment of detrusor instability.     

Verapamil versus saline in electromotive drug administration for Peyronie's disease: a double-blind, placebo controlled trial

PURPOSE: While surgery remains the gold standard of therapy to correct the acquired curvature of Peyronie's disease, the search for a less invasive therapy continues. Transdermal drug delivery was proposed to be superior to oral or injection therapy because it bypasses hepatic metabolism and minimizes the pain of injection. After electromotive drug administration with verapamil tunica albuginea specimens were demonstrated to contain detectable levels of the drug. Due to varying success with verapamil as injectable therapy for Peyronie's disease we performed a double-blind, placebo controlled trial to determine the effectiveness of verapamil delivered through electromotive drug administration. MATERIALS AND METHODS: A total of 42 men with Peyronie's disease volunteered to participate in this study, which was approved by our institutional review board. A genitourinary examination was performed on all patients, including plaque location, stretched penile length, objective measurement of curvature after papaverine injection and duplex ultrasound. Each subject was randomized to receive 10 mg verapamil in 4 cc saline or 4 cc saline via electromotive drug administration. A Mini-Physionizer (Physion, Mirandola, Italy) device was used at a power of 2.4 mA for 20 minutes. Treatments were performed 2 times weekly for 3 months. After 3 months each patient was reevaluated with physical examination and duplex ultrasound by a technician blinded to the treatment received. A modified erectile dysfunction index of treatment satisfaction questionnaire was also completed by each patient. RESULTS: A total of 23 patients were randomized to the verapamil treatment group (group 1) and 19 were randomized to the saline group (group 2). There were no significant differences between patient groups with respect to patient age, disease duration or pretreatment curvature. In group 1, 15 patients (65%) had measured improvement (mean 9.1 degrees, range 5 to 30), 5 (22%) had no change and in 3 (13%) the condition worsened. In group 2, 11 patients (58%) had measured improvement (mean 7.6 degrees, range 5 to 30), 7 (37%) showed no change and in 1 (5%) the condition worsened. To better evaluate effectiveness the total number of patients experiencing significant improvement (20 degrees or greater) was calculated and compared. Seven patients (30%) in group 1 and 4 (21%) in group 2 achieved this criterion. Although a greater percent of patients treated with verapamil had improved curvature, the results were not statistically significant. CONCLUSIONS: Although a greater percent of patients treated with verapamil in our electromotive drug administration protocol had a measured decrease in curvature, the results were not statistically significant. Further research is necessary to determine whether electric current may have a role in the treatment of Peyronie's disease as well as if verapamil delivered via electromotive drug administration may have a role as effective treatment. Electromotive drug administration is a treatment option in the patient whose major complaint is pain or in the patient with mild curvature who does not wish to undergo intralesional therapy or surgical correction.     

Clinical trial of bromhexine in severe chronic bronchitics during winter

In a double-blind, controlled cross-over trial, the effect of the mucolytic drug bromhexine (24 mg or 48 mg daily) was compared with a placebo over a period of 14 weeks in 21 severe chronic bronchitics (mean FEV_1·0 0·8 1.). Each of the three treatment regimes was continued for four weeks with intervening single weeks on placebo tablets. As the subjects were outpatients, sodium fluorescein incorporated in the tablets was used as a drug marker. Satisfactory data were obtained in 18 patients. There was no significant improvement in clinical condition or ventilatory capacity nor change in sputum properties throughout the period of study. No side effects or significant change in blood values were detected.     

Teriparatide increases bone formation in modeling and remodeling osteons and enhances IGF-II immunoreactivity in postmenopausal women with osteoporosis.

Transiliac bone biopsies were obtained from 55 women treated with teriparatide or placebo for 12-24 months. We report direct evidence that modeling bone formation at quiescent surfaces was present only in teriparatide-treated patients and bone formation at remodeling sites was higher with teriparatide than placebo. INTRODUCTION: Recombinant teriparatide [human PTH(1-34)], a bone formation agent for the treatment of osteoporosis when given once daily subcutaneously, increases biochemical markers of bone turnover and activation frequency in histomorphometry studies. MATERIALS AND METHODS: We studied the mechanisms underlying this bone-forming action of teriparatide at the basic multicellular unit by the appearance of cement lines, a method used to directly classify surfaces as modeling or remodeling osteons, and by the immunolocalization of IGF-I and IGF-II. Transiliac bone biopsies were obtained from 55 postmenopausal women treated with teriparatide 20 or 40 microg or placebo for 12-24 months (median, 19.8 months) in the Fracture Prevention Trial. RESULTS: A dose-dependent relationship was observed in modeling and mixed remodeling/modeling trabecular hemiosteons. Trabecular and endosteal hemiosteon mean wall thicknesses were significantly higher in both teriparatide groups than in placebo. There was a dose-dependent relationship in IGF-II immunoreactive staining at all bone envelopes studied. The greater local IGF-II presence after treatment with teriparatide may play a key role in stimulating bone formation. CONCLUSIONS: Direct evidence is presented that 12-24 months of teriparatide treatment induced modeling bone formation at quiescent surfaces and resulted in greater bone formation at remodeling sites, relative to placebo.     

Assessment of cognitive function of the elderly population: effects of darifenacin

PURPOSE: Overactive bladder is common in the elderly population, which is susceptible to cognitive disorders and drug induced cognitive impairment. Existing overactive bladder treatments may cause adverse events, such as cognitive impairment, due to antagonism of the M1 receptor in the central nervous system. In this study we evaluated the effect of darifenacin, an M3 selective antagonist, on cognitive function in elderly volunteers without clinical dementia. MATERIALS AND METHODS: This double-blind, 3-period crossover study randomized 129 volunteers 65 years or older with no/mild cognitive impairment to receive 3 of 5 treatments, namely darifenacin controlled release (3.75, 7.5 or 15 mg once daily), darifenacin immediate-release (5 mg 3 times daily) or matching placebo for 14 days. Each treatment period was separated by 7 days of washout. Cognitive function tests were completed at baseline and at treatment end. RESULTS: For the primary end points of memory scanning sensitivity, speed of choice reaction time and word recognition sensitivity, there were no statistically significant differences for darifenacin vs placebo. There were no statistically significant differences in secondary variables except memory scanning speed, which increased in all groups relative to baseline, but improvement was greater with placebo than with 3.75 mg darifenacin. Darifenacin treatment was not associated with changes in alertness, contentment or calmness, which are likely to be clinically relevant. Darifenacin was well tolerated. CONCLUSIONS:: In elderly volunteers 2 weeks of treatment with darifenacin had no effect on cognitive function compared with baseline and it was not significantly different from placebo. This may be related to its M3 receptor selectivity with negligible M1 receptor antagonism.     

Candicidin in treatment of benign prostatic hypertrophy

In a prospective, double-blind, placebo-controlled multicenter study, candicidin (a polyene macrolide) was investigated in the treatment of benign prostatic hypertrophy. Seventy-six patients were included in the study--34 in the candicidin group and 42 in the placebo group. Patients treated with 270 mg. of candicidin daily for 6 months had a significant decrease in residual urine, voided volume and bladder volume. No significant increases were found in flow rates. Symptoms improved significantly in both the candicidin and the placebo group, but no differences in improvement were found between the groups. The results of candicidin treatment are less satisfactory than those following surgery.     

The effect of withdrawal of drugs treating intermittent claudication.

BACKGROUND: Pharmacologic treatment for intermittent claudication is a management option. This study evaluated the effect of withdrawal of drug therapies, cilostazol and pentoxifylline, on the walking ability of peripheral artery disease patients. METHODS: Single-blind placebo crossover from a randomized, double-blind trial; 45 claudication patients received either cilostazol 100 mg orally twice daily (n = 16), pentoxifylline 400 mg orally three times daily (n = 13), or placebo (n = 16) for 24 weeks. After 24 weeks of double-blind therapy, treatment for all groups was placebo only, and follow-up continued through week 30. Treatment efficacy was established with treadmill testing. RESULTS: Profile analysis demonstrated a highly significant loss of treatment benefit after crossover (P = 0.001) for cilostazol-treated patients, but no significant change after crossover was observed with pentoxifylline. CONCLUSIONS: Drug withdrawal worsened the walking of claudicants who had benefited from cilostazol therapy. This decline with crossover to placebo suggests that the initial improvement with cilostazol treatment was due to the drug's action. Withdrawal of pentoxifylline did not adversely affect walking.     

Parlodel treatment of uremic hypogonadism in men

Parlodel, 2.5 mg daily, was given during 1-3 months to 14 uremic hypogonadal patients (placebo controlled in 6). Except for a decrease in serum prolactin levels on Parlodel (p less than 0.01), no significant changes in hormonal values (gonadotropins and testosterone) were observed either on Parlodel or on placebo. Parlodel treatment improved the potency of 10 patients, eliminated gynecomastia in 2 and normalized spermatogenesis in 6; the best results were obtained in patients on low-protein diet. On placebo, potency improved only in 1 patient; no improvement in spermatogenesis was registered. Thus, Parlodel can improve sexual function and spermatogenesis in hypogonadal uremic males.     

Tamsulosin 0.4 mg once daily: effect on sexual function in patients with lower urinary tract symptoms suggestive of benign prostatic obstruction.

OBJECTIVE: To evaluate the effect of tamsulosin, 0.4 mg once daily, on sexual function in comparison with placebo and alfuzosin, 2.5 mg three times daily, in patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO). METHODS: Data from 830 patients randomized into three European multicenter studies with similar protocols were analyzed. In two studies, patients were randomized to receive either tamsulosin, 0.4 mg once daily, or placebo, and in the third, patients were randomized to receive either a fixed dose of tamsulosin, 0.4 mg once daily, or alfuzosin, titrated to 2.5 mg three times daily. The studies employed a 2-week placebo run-in period, followed by a 12-week study period. Sexual function was assessed by related adverse events and by a sexual function score determined from a life-style questionnaire. RESULTS: Abnormal ejaculation occurred significantly more frequently in patients treated with tamsulosin than in those receiving placebo (p = 0.045); however, the incidence of abnormal ejaculation was similar in patients receiving tamsulosin or alfuzosin in the comparative study. Abnormal ejaculation was not perceived as a major problem by the patients since it resulted in few treatment discontinuations (n = 3). It was also reversible on drug withdrawal. There was no difference between tamsulosin and placebo or alfuzosin with regard to the occurrence of decreased libido or impotence. In addition, there was no significant difference in the change in sexual function score between patients treated with tamsulosin and those treated with alfuzosin. Compared with patients receiving placebo, there was, however, a significant improvement in total sexual function score in patients receiving tamsulosin (p = 0.042). CONCLUSIONS: Tamsulosin, 0.4 mg once daily, is well tolerated and has no overall negative impact on sexual function compared with placebo or alfuzosin. Compared with placebo, tamsulosin may even improve sexual function.     

Immunobiotherapy with Uro-Vaxom in recurrent urinary tract infection. The German Urinary Tract Infection Study Group

A series of 120 patients with recurrent urinary tract infection (UTI), all in acute recurrence at the start of the trial, were treated for 3 months under double-blind conditions with 1 capsule daily of either the immunobiotherapeutic product Uro-Vaxom (UV) or a placebo. They were then observed for 3 months without treatment. During the 6 months of the trial a significant decrease was noted in the UV group compared with the placebo group with respect to the number of recurrences of UTI, total consumption of antibiotics and chemotherapeutic agents, bacteriuria and dysuria. By the sixth month the UV patients were receiving no antibiotics. The final assessment was that UV was significantly more effective than the placebo. UV was well tolerated, with possible mild side effects in only 4 patients. During a further observation period of 5 months, patients who had received UV during the first period had fewer recurrences of UTI than those who had received placebo, confirming the long-term protective action of UV.     

Increased warning time with darifenacin: a new concept in the management of urinary urgency

PURPOSE: We assessed the effect of darifenacin, an M3 selective receptor antagonist, on the warning time associated with urinary urgency. MATERIALS AND METHODS: In this multicenter, double-blind study subjects with urinary urgency for 6 months or greater and episodes of urgency 4 times or greater daily were randomized to darifenacin controlled release tablets (30 mg once daily) or placebo. Warning time was defined as the time from the first sensation of urgency to voluntary micturition or incontinence. Data were collected using electronic event recorders during 6-hour clinic visits or 3 urge-void cycles, if shorter, at baseline and at treatment end. RESULTS: A total of 72 subjects entered the study and 67 were included in the primary efficacy analysis (darifenacin in 32 and placebo in 35). Darifenacin treatment resulted in a significant increase in mean warning time with a median increase of 4.3 minutes compared with placebo (p = 0.003). Overall 47% of darifenacin treated subjects compared with 20% receiving placebo achieved a 30% increase or greater in mean warning time (OR 5.6, p = 0.009). Median and minimum warning times were also significantly increased following darifenacin treatment vs placebo (p = 0.004 and 0.017, respectively). The median difference in minimum warning time was 1.9 minutes in favor of darifenacin vs placebo. CONCLUSIONS: To our knowledge this is the first study to evaluate change in warning time, which is potentially important to individuals with symptoms associated with overactive bladder. Darifenacin increases mean, median and minimum warning time compared with placebo, allowing subjects more time to reach a toilet and potentially avoiding the embarrassing experience of incontinence.     

Psychological changes and improvement in chronic airflow limitation after corticosteroid treatment.

Corticosteroids may produce mood changes. This could account for improvement in patients with chronic airflow limitation following trials of oral corticosteroid treatment as mood elevation might improve performance in objective measurements. This proposition was tested in 21 patients with chronic airflow limitation, who underwent detailed psychological assessment during a randomised controlled double blind crossover trial of the effect of prednisolone 40 mg daily compared with that of a placebo. Self rating visual analogue scales for various qualities of mood were completed before the study and after each phase in addition to depression and psychological symptom questionnaires. After treatment with the placebo, patients showed increases in cheerfulness (p less than 0.01) and sociability (p less than 0.01) and a decrease in depression (p less than 0.01). After treatment with prednisolone there were increases in cheerfulness (p less than 0.01), optimism (p less than 0.01), activity (p less than 0.05), and sociability (p less than 0.02) and there was a decrease in depression (p less than 0.01). When placebo and prednisolone values were compared, however, there were no significant differences. Some patients showed improvements (greater than 20%) in peak expiratory flow, FEV1 or forced vital capacity (FVC) after prednisolone, but nearly all had improvements in at least one psychological test. There were no detectable associations between changes in objective measurements and changes in psychological test ratings. This study suggests that in patients with chronic obstructive lung disease significant psychological changes are no more likely to follow treatment with a corticosteroid than treatment with a placebo and that physiological improvement after corticosteroid treatment is not tied to psychological changes.     

Double-blind trial of the efficacy and tolerability of doxazosin in the gastrointestinal therapeutic system, doxazosin standard, and placebo in patients with benign prostatic hyperplasia

BACKGROUND: The alpha(1)-blocker doxazosin mesylate is an established efficacious and welltolerated treatment for benign prostatic hyperplasia (PBH). However, its clinical utility can be limited by the need for multiple titration steps, starting at an initial dose of 1 mg, increased up to 8 mg once daily, to achieve optimal therapeutic response. A new controlled-release gastrointestinal therapeutic system (GITS) formulation of doxazosin mesylate enhances the pharmacokinetic profile and drug delivery rate, reducing the plasma doxazosin mesylate peak-to-trough ratio and minimizing the need for titration. OBJECTIVE: A study was conducted to assess the effects of doxazosin GITS 4 or 8 mg once daily, doxazosin standard 1 mg to 8 mg once daily, and placebo, in 795 men with BPH. This randomized, double-blind, multicenter Scandinavian study included a 2-week washout period, 2-week single-blind placebo run-in phase, and 13-week double-blind treatment phase. Doxazosin GITS was initiated at 4 mg once daily and titrated to 8 mg once daily after 7 weeks, if indicated, and doxazosin standard was initiated at 1 mg once daily, titrated to 2 mg after 1 week, to 4 mg at 3 weeks, and to 8 mg at 7 weeks if indicated, to achieve symptom control. The primary outcome measures were mean changes from baseline to the final visit for International Prostate Symptom Score (I-PSS) and maximum urinary flow rate adjusted for baseline values. RESULTS: Both doxazosin GITS and doxazosin standard significantly improved the symptoms of BPH, as evidenced by least-squares mean reductions in total I-PSS of -8.0+/-0.3 and -8.4+/-0.3 from baseline, respectively, compared with a reduction of -6.0+/-0.4 in patients on placebo. Doxazosin GITS and doxazosin standard produced clinically comparable improvements in maximum urinary flow rates, with a greater improvement observed earlier following treatment with doxazosin GITS than with doxazosin standard. Both active treatments produced significantly greater increases in maximum urinary flow rate compared with placebo. Nearly half of the patients on doxazosin GITS achieved symptom relief at the 4-mg starting dose. A similar number of patients in both doxazosin groups were titrated to the maximum dose of 8 mg for both formulations. The overall incidence of adverse events was similar among patients treated with doxazosin GITS and placebo, and slightly higher in those on doxazosin standard. There was no apparent difference in the type of adverse events reported for the two formulations of doxazosin, although most adverse events were reported at a lower frequency with doxazosin GITS. CONCLUSIONS: Doxazosin GITS is significantly more effective than placebo in reducing the clinical symptoms of BPH and improving maximum urinary flow rate, and as effective as doxazosin standard. A therapeutic effect equivalent to that of doxazosin standard was achieved with doxazosin GITS with fewer titration steps, in a manner that appeared to be better tolerated. Because treatment with doxazosin GITS starts with an effective dose for many patients, it is likely that this clinical profile will result in the need for fewer patient visits than with doxazosin standard therapy.     

Treating thermally injured children suffering symptoms of acute stress with imipramine and fluoxetine: a randomized, double-blind study

Introduction. For pediatric burn patients with the symptoms of acute stress disorder (ASD) a first line medication is not widely agreed upon. A prospective, randomized, placebo controlled, double-blind design was used to test the efficacy of imipramine and fluoxetine. Method. Patients 4-18 years of age with symptoms of ASD were randomized to 1 of 3 groups: imipramine, fluoxetine, or placebo for 1 week. Daily imipramine dose was 1mg/kg, with the maximum dose being 100mg. Daily fluoxetine dose was 5mg for children weighing >/=40kg; 10mg for those weighing between 40 and 60kg; 20mg for those weighing >60kg. Results. Sixty participants, 16 females and 44 males, had an average body surface area burn of 53% (S.D.=18) and average age of 11 years (S.D.=4). Imipramine subjects received an average daily dose of 1.00+/-0.29mg/kg. Fluoxetine subjects received an average daily dose of 0.29+/-0.16mg/kg. Between group differences were not detected. Fifty-five percent responded positively to placebo; 60% responded positively to imipramine; and 72% responded positively to fluoxetine. Conclusion. Within the parameters of this study design and sample, placebo was statistically as effective as either drug in treating symptoms of ASD.