A second phase III multicenter placebo controlled study of 2 dosages of modified release tamsulosin in patients with symptoms of benign prostatic hyperplasia. United States 93-01 Study Group

PURPOSE: In a double-blind, phase III clinical trial we evaluate the safety and efficacy of 0.4 and 0.8 mg. tamsulosin daily for the treatment of patients with symptoms of moderate to severe benign prostatic hyperplasia. MATERIALS AND METHODS: Patients meeting the basic requirements of the study underwent a 4-week single-blind placebo evaluation period. A total of 735 patients were randomized to double-blind therapy with tamsulosin or placebo. Treatment duration was 13 weeks. Efficacy and safety were evaluated at 5 visits during the double-blind treatment period. RESULTS: When efficacy data between baseline and end point were compared there was a significant reduction in total American Urological Association symptom score (25%) in each tamsulosin group compared with placebo (p = 0.01) and the percentage of patients with a 30% or more reduction in peak urinary flow rate was significantly greater in the tamsulosin versus placebo group (p <0.05). Improvements in American Urological Association symptom scores and maximum flow rate occurred at 1 week of treatment. None of the patients experienced a first dose effect. There were no significant changes in blood pressure on standing at any visit during the study except for a decrease in systolic blood pressure of 20 mm. Hg or more between the 0.8 mg. dose and placebo groups at visit 4 (p = 0.036). Positive orthostatic tests were significantly more frequent in the 0.8 mg. group compared with placebo at visit 4 (p = 0.012). The treatment groups did not differ significantly in incidence of electrocardiogram abnormalities at each post-baseline visit and at end point. CONCLUSIONS: Tamsulosin was safe and effective, and clinically and statistically superior to placebo in relieving symptoms of benign prostatic hyperplasia in men with moderate to severe symptoms at baseline. There was no evidence of a first dose effect and no clinically significant orthostatic hypertension. In addition, response to treatment was rapid.     

Comparison of tamsulosin with alfuzosin in the treatment of patients with lower urinary tract symptoms suggestive of bladder outlet obstruction (symptomatic benign prostatic hyperplasia). The European Tamsulosin Study Group

OBJECTIVE: To compare the efficacy and tolerability of the alpha 1 A-subtype selective drug tamsulosin with the nonsubtype-selective agent alfuzosin in the treatment of patients with lower urinary tract symptoms (LUTS) suggestive of bladder outlet obstruction (BOO), often termed symptomatic benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: The study comprised 256 patients with benign prostatic enlargement and LUTS suggestive of BOO (symptomatic BPH) who received tamsulosin 0.4 mg once daily or alfuzosin 2.5 mg three times daily during 12 weeks of treatment. The response was assessed by measurements of maximum urinary flow rate (Qmax), a symptom score (Boyarsky) and blood pressure at regular intervals. RESULTS: Tamsulosin and alfuzosin produced comparable improvements in Qmax and total Boyarsky symptom score. Both treatments were well tolerated with respect to adverse events. Tamsulosin had no statistically significant effect on blood pressure compared with baseline but alfuzosin induced a significant reduction in both standing and supine blood pressure, compared with baseline (P < 0.05). CONCLUSION: Tamsulosin is the first adrenoceptor antagonist that is selective for the alpha 1 A-subtype; this specificity may explain its lack of effect on blood pressure compared with alfuzosin, an agent that is not receptor subtype specific. Moreover, this finding may partly explain why tamsulosin, in contrast to other currently available alpha 1-adrenoceptor antagonists, can be administered without dose titration. Another advantage compared with alfuzosin (and prazosin) is the once-daily dosing regimen of tamsulosin.     

Bone marrow relapse in high-risk pediatric patients with acute lymphoblastic leukemia: a comparison of relapse times and initial clinical features of patients on different protocols. Children''s Cancer and Leukemia Study group (CCLSG)

Alpha adrenergic blocker has become the first choice in the medical treatment of benign prostatic hyperplasia (BPH). The efficacy of alpha adrenergic blocker has been suggested to be related to the prostatic tissue components, and to be ineffective in treating the clinical symptoms caused by BPH in some cases. The efficacy and prostate reduction of an anti-androgenic agent, chlormadinone acetate, combined with alpha adrenergic blocker, tamsulosin hydrochloride, were evaluated using 40-BPH patients insufficiently treated with tamsulosin hydrochloride alone. Fifty mg of chlormadinone acetate and 0.2 mg of tamsulosin hydrochloride were administered orally once a day for 16 weeks to patients with a prostate subjective symptoms score, I-PSS, of greater than 13 or a peak flow rate of less than 12 ml/s, even after the treatment with 0.2 mg of tamsulosin hydrochloride alone for more than four weeks. Total I-PSS decreased significantly after four weeks. The total irritative symptom score did not change for 16 weeks, but the total obstructive symptom score decreased significantly, as did the total I-PSS. In objective data, the estimated volume of both total prostate and the transition zone on transrectal ultrasonogram decreased significantly at the end of the treatment, and the peak flow rate decreased significantly after 12 weeks. These findings suggest that the addition of chlormadinone acetate may be a reasonable alternative in the treatment of BPH patients responding insufficiently to tamsulosin hydrochloride alone, and that combination therapy using chlormadinone acetate and tamsulosin hydrochloride may be useful for BPH patients with serious obstructive symptoms.     

Doxazosin in the treatment of benign prostatic hyperplasia in normotensive patients: a multicenter study

A 16-week, double-blind, placebo controlled, dose titration study was done on 100 normotensive patients age 45 years or older to determine the efficacy and safety of doxazosin, a selective alpha 1-adrenoceptor antagonist, in the treatment of benign prostatic hyperplasia (BPH). Of the 41 efficacy evaluable patients 88% underwent dose titration to a maximum of 8 mg. doxazosin once daily. Maximum and average urinary flow rates increased significantly above baseline with doxazosin (2.9 ml. per second and 1.4 ml. per second, respectively) compared with placebo (0.7 ml. per second and 0.3 ml. per second, respectively). A significant effect on maximum flow rate was noted as early as week 2 of double-blind treatment at the initial efficacy evaluation. Doxazosin was superior to placebo in patient and investigator assessments of total, obstructive and irritative BPH symptoms. The onset of efficacy for total patient-assessed symptoms was significant for doxazosin compared to placebo 4 weeks after the start of the treatment regimen. Statistically significant decreases in mean blood pressure of 4 to 6 mm. Hg were noted with doxazosin compared with placebo. Adverse events, primarily mild to moderate in severity, were reported in 44% of patients given doxazosin and 30% of those given placebo. Our results strongly demonstrate that doxazosin is significantly superior to placebo in the treatment of BPH in normotensive patients, with the patient experiencing significant relief early after initiation of therapy.     

Transdermal nitroglycerin patch therapy improves left ventricular function and prevents remodeling after acute myocardial infarction: results of a multicenter prospective randomized, double-blind, placebo-controlled trial

BACKGROUND: Nitrates are widely used in the treatment of angina in patients with acute myocardial infarction (AMI). Short-term administration prevents left ventricular (LV) dilation and infarct expansion. However, little information is available regarding their long-term effects on LV remodeling in patients surviving Q-wave AMI. METHODS AND RESULTS: This was a randomized, double-blind, placebo-controlled trial designed to investigate the long-term (6-month) efficacy of intermittent transdermal nitroglycerin (NTG) patches on LV remodeling in 291 survivors of AMI. Patients meeting entry criteria had baseline gated radionuclide angiography (RNA) followed by randomization to placebo or active NTG patches delivering 0.4-, 0.8-, or 1.6-mg/h. RNA was repeated at 6 months and 6.5 days after withdrawal of double-blind medication. The primary study end point was the change in end-systolic volume index (ESVI). Both ESVI and end-diastolic volume index (EDVI) were significantly reduced with 0.4-mg/h NTG patches (-11.4 and -11.6 mL/m2, respectively, P<.03). This beneficial effect was observed primarily in patients with a baseline LV ejection fraction < or =40% (deltaESVI, -31 mL/m2; deltaEDVI, -33 mL/m2; both P<.05) and only at the 0.4-mg/h dose. After NTG patch withdrawal, ESVI significantly increased but did not reach pretreatment values. CONCLUSIONS: Transdermal NTG patches prevent LV dilation in patients surviving AMI. The beneficial effects are limited to patients with depressed LV function and only at the lowest (0.4-mg/h) dose. Continued administration is necessary to maintain efficacy. Whether these remodeling effects confer a clinical or survival advantage will need to be addressed in an adequately powered cardiac event trial.     

Current state of knowledge concerning the mechanisms of action of BCG

OBJECTIVES: To report the safety and efficacy of the transurethral needle ablation (TUNA) procedure for the treatment of clinical benign prostatic hyperplasia (BPH). METHODS: One hundred thirty patients with BPH were enrolled in two identical protocols and treated by the TUNA procedure. Entry criteria included an American Urological Association symptom index (AUA SI) of 13 points or higher and a peak flow rate of 12 mL/s or less. Patients were followed up for 12 months. Efficacy parameters included the AUA SI, AUA problem index, BPH impact index (BPH II), quality of life (QOL) score, and peak flow rate. At each visit, side effects were elicited. Follow-up data are available for 93 patients at 12 months. All patients were given intraurethral lidocaine augmented by oral and/or parenteral sedation. No patient received spinal or general anesthesia. RESULTS: All patients tolerated the procedure well, and there were no deaths. Forty-one percent of patients (n = 53) had a catheter placed immediately after the procedure. At 12 months, the AUA SI had decreased from 23.7 to 11.9 (P < 0.0001) and the BPH II from 7.5 to 2.5 (P < 0.0001), whereas the peak flow rate had increased from 8.7 to 14.6 mL/s (P < 0.0001). Irritative voiding symptoms were noted in 20 patients (16%) at some point during follow-up. Two patients reported erectile dysfunction, and 1 reported retrograde ejaculation. CONCLUSIONS: In this prospective study of 130 patients with clinical BPH and lower urinary tract symptoms, TUNA provided substantive and lasting improvement according to AUA SI, BPH II, and QOL scores as well as peak flow rate over 1 year. The TUNA procedure was well tolerated, with few major side effects and complications noted. Longer follow-up is needed to document the maintenance of clinical benefit beyond 12 months.     

Two factors of experienced deficits in schizophrenia and their relationships with positive, negative, and depressive symptoms

Benign prostatic hyperplasia (BPH) is the most common benign tumor in men and is responsible for urinary symptoms in the majority of men older than 50 years of age. Although transurethral resection of the prostate (TURP) is the gold standard, its complications have impacted upon its utility. As a consequence, new pharmacologic and minimally invasive approaches to the management of BPH have been developed. One minimally invasive approach that employs interstitial laser coagulation by the Indigo 830e LaserOptic system heats the prostate to the point of irreversible necrosis while preserving the urethral lining, potentially resulting in fewer complications. To test the efficacy of this device we evaluated the interim results obtained in 25 patients treated for BPH. Parameters evaluated included the AUA symptom score, uroflowometry, post-void residual, and prostate size. Following treatment, patients were discharged home and the catheter was removed within 3-7 days. Patients were assessed at 1 month and at subsequent 3-month intervals following the procedure using a questionnaire, AUA symptom score, and uroflowometry. The results of the paired t-tests demonstrated a significant increase in the maximal and average flow rates from baseline. The mean baseline maximal flow rate was 8.3 ml/s and increased to 10, 12.7, 14.1, and 12.0 ml/s at 1, 3, 6, and 9 months, respectively, and the mean baseline average flow rate was 4.4 ml/s and increased to 5.3, 6.0, 6.6, and 6.2 ml/s at 1, 3, 6, and 9 months, respectively. The AUA symptom scores decreased from 20.2 to 9.8 at 9 months. There was no intraoperative complication. Six patients developed transient retention. No patient developed bladder neck contractures, urinary incontinence, impotence, or urinary tract infections. One patient developed retrograde ejaculation and one patient required retreatment by TURP. Hence, improvements in symptom scores and voiding parameters suggest that the laser interstitial coagulation prostatectomy is safe and effective for the treatment of BPH.     

Safety, pharmacokinetics, and antiretroviral activity of intravenous 9-[2-(R)-(Phosphonomethoxy)propyl]adenine, a novel anti-human immunodeficiency virus (HIV) therapy, in HIV-infected adults

9-[2-(R)-(Phosphonomethoxy)propyl]adenine (PMPA) is a nucleotide analogue with potent antiretroviral activity in vitro and in simian models. A randomized, double-blind, placebo-controlled, dose-escalation clinical trial of intravenous PMPA monotherapy was conducted in 20 human immunodeficiency virus (HIV)-infected adults with CD4 cell counts of >/=200 cells/mm3 and plasma HIV RNA levels of >/=10,000 copies/ml. Two dose levels were evaluated (1 and 3 mg/kg of body weight/day). Ten subjects were enrolled at each dose level (eight randomized to receive PMPA and two randomized to receive placebo). On day 1, a single dose of PMPA or placebo was administered by intravenous infusion. Beginning on study day 8, PMPA or placebo was administered once daily for an additional 7 consecutive days. All subjects tolerated dosing without significant adverse events. Mean peak serum PMPA concentrations were 2.7 +/- 0.9 and 9.1 +/- 2.1 microgram/ml in the 1- and 3-mg/kg cohorts, respectively. Serum concentrations declined in a biexponential fashion, with a terminal half-life of 4 to 8 h. At 3 mg/kg/day, a single infusion of PMPA resulted in a 0.4 log10 median decline in plasma HIV RNA by study day 8. Following 7 consecutive days of study drug administration thereafter, the median changes in plasma HIV RNA from baseline were -1.1, -0.6, and 0.1 log10 in the 3-mg/kg/day, 1-mg/kg/day, and placebo dose groups, respectively. Following the final dose in the 3-mg/kg/day cohort, the reduction in HIV RNA was sustained for 7 days before returning toward baseline. Further studies evaluating an oral prodrug of PMPA are under way.     

The American Urological Association symptom index for benign prostatic hyperplasia as a function of age, volume and ultrasonic appearance of the prostate

PURPOSE: Our study was conducted to reveal quantitatively the relative effects of age and ultrasonic appearance of benign prostatic hyperplasia (BPH) on urinary symptoms as evaluated by the American Urological Association (AUA) symptom index score. MATERIALS AND METHODS: In 929 examinees (732 with a normal prostate and 197 with BPH) on a mass screening program for prostatic diseases using transrectal ultrasonography in Japan, the AUA symptom score was compared to age, prostatic volume and presumed circle area ratio using simple and multiple regression analyses. RESULTS: Simple regression analysis demonstrated the symptom score to correlate significantly with age (R = 0.162, p < 0.0001), prostatic volume (R = 0.072, p = 0.0281) and presumed circle area ratio (R = 0.150, p < 0.0001). However, multiple regression analysis demonstrated that age and presumed circle area ratio were significant independent determinants of the total symptom score. Among 7 symptoms included in the AUA symptom index weak stream and hesitancy scores were not influenced by age, prostatic volume or presumed circle area ratio. CONCLUSIONS: As a parameter representing the degree of BPH in terms of the severity of urinary symptoms, presumed circle area ratio was preferable to prostatic volume. Regression analyses confirmed again that the AUA symptom index was influenced considerably by age and was not specific to BPH.     

Loss of Bcl-2 expression correlates with tumour recurrence in colorectal cancer

OBJECTIVE: To analyse the efficacy, correlations and adverse-event profile of placebo therapy from the initial placebo run-in period to beyond 2 years of treatment. PATIENTS AND METHODS: The effects of placebo therapy on prostate size, maximum urinary flow rate (Qmax) and symptoms were analysed, and adverse drug experiences documented, for a period of 25 months in 303 patients randomized to the placebo arm of a controlled trial evaluating finasteride in the treatment of BPH (the Canadian PROSPECT study). RESULTS: For all variables, the values during follow-up were significantly different from baseline (P < or = 0.001). Transrectal ultrasonography confirmed a progressive increase in prostate volume over 25 months (+8.4%) but Qmax improved for the first 5 months (to 1.4 mL/s over baseline) and remained 1.0 mL/s more than baseline at 25 months. The total symptom score improved by -2.9 points in the first 2 months on placebo and was ultimately 2.3 points below baseline at 25 months. The extent of the placebo response for symptoms (r=0.08, P=.180) and Qmax (r=0.04, P=0.550) was independent of age, but the response correlated with the initial severity of symptoms (r= -0.394, P < or = 0.001) and initial Qmax (r= -0.134, P=0.023). Patients with a prostate of < or = 40 mL had a clinically more important placebo response than those with larger prostates. In all, 246 patients (81.2%) reported adverse events thought to be secondary to placebo therapy. The most common complaint was urogenital (40.3%), specifically impotence (6.3%) and decreased libido (6.3%); 13.2% of patients discontinued placebo therapy because of significant adverse reactions. CONCLUSIONS: Placebo therapy rapidly produces a significant improvement in Qmax and symptoms of BPH but also causes clinically important adverse effects. The beneficial effect fades but remains after 2 years.     

American Urological Association symptom index in the assessment of urethroplasty outcomes

PURPOSE: In men undergoing urethroplasty we used the American Urological Association (AUA) symptom index to assess the magnitude of symptoms and determine the validity of this index as an outcome assessment tool. MATERIALS AND METHODS: The AUA symptom index was completed by individual interview of 50 men a mean of 41 years old who underwent urethral reconstruction. Symptom scores were then correlated with radiographic retrograde urethrograms and urinary flow rates to determine whether changes in the score were consistent with these other clinical indicators of success or failure. RESULTS: Mean preoperative AUA symptom index score in all evaluable patients was 26.9 (maximum 35), indicating severely bothersome voiding symptoms. In patients with radiographic evidence of successful urethral reconstruction the average postoperative score was 5.1 (p <0.0001). In those with recurrent stricture after urethroplasty scores were essentially unchanged but after successful repeat urethroplasty the mean symptom index score decreased to 3.4 (p <0.0001). A statistically significant inverse correlation (r = -0.712, p <0.0001) was found between AUA symptom index scores and maximum urinary flow rates. CONCLUSIONS: Patients with urethral strictures who are selected for formal urethroplasty have severe obstructive and irritative voiding symptoms. Results of the AUA symptom index correlate closely with conventional measures of urethroplasty outcome, such as radiographic retrograde urethrography and urinary flow studies. The AUA symptom index appears to have clinical validity as an adjunctive outcome assessment tool after urethroplasty.     

Oxybutynin in the treatment of early detrusor instability after transurethral resection of the prostate

OBJECTIVE: To evaluate the symptomatic and urodynamic effects of oxybutynin in the control of irritative micturitional symptoms during the first week after transurethral resection of benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: Fifty-three patients (median age 67 years, interquartile range 62-72) were included prospectively in a double-blind placebo-controlled study. Pre-operatively, uroflowmetry and cystometrography (CMG) were performed, and the post-void residual volume (PVR) measured; symptoms were rated according to the Boyarski score. CMG was repeated on the first post-operative day and medication was started on the third day. Before withdrawing the catheter on the fifth day. CMG was repeated. Three days later, symptoms were evaluated according to the Boyarski score and uroflowmetry and the estimate of PVR reassessed. RESULTS: In comparison with placebo, oxybutynin significantly decreased frequency, urgency and detrusor pressure at first sensation of filling. However, oxybutynin did not lower the rate of pre-operative detrusor instability and exerted no effect on the maximal capacity of the bladder and corresponding detrusor pressure. Dryness of mouth was reported in 13% and 65% of patients receiving placebo and oxybutynin, respectively. CONCLUSION: Oxybutynin alleviates early irritative symptoms after transurethral resection of BPH, without consistently modifying bladder urodynamics.     

Neoadjuvant and adjuvant alpha-blockade improves early results of high-energy transurethral microwave thermotherapy for lower urinary tract symptoms of benign prostatic hyperplasia: a randomized, prospective clinical trial

OBJECTIVES: Improved long-term results with respect to symptoms, voiding function, and quality of life (QOL) in patients with lower urinary tract symptoms (LUTS) of benign prostatic hyperplasia (BPH) are achieved with targeted high-energy transurethral microwave thermotherapy (TUMT) compared with alpha-blocker treatment alone. However, maximal improvement after TUMT is not attained until 3 to 6 months after treatment. Measures to provide earlier symptom relief and improved voiding function and QOL would add to the clinical utility of TUMT. The objective of the present study was to determine whether neoadjuvant and adjuvant alpha-blockade is capable of accelerating a post-TUMT decrease in LUTS of patients with BPH. METHODS: In this randomized, prospective study of 81 patients with LUTS of BPH, 41 underwent TUMT with neoadjuvant and adjuvant tamsulosin (0.4 mg daily) treatment, and 40 had TUMT alone. International Prostate Symptom Score (IPSS), peak urinary flow rate (Qmax), and QOL score were determined before treatment and at periodic intervals thereafter up to 12 weeks after TUMT. RESULTS: Mean IPSS values in the TUMT plus tamsulosin group at 2 weeks (14.0, 95% confidence interval [CI] 13.1 to 14.9) and 6 weeks (8.6; 95% CI 7.7 to 9.5) were 15% and 24% lower, respectively, than those at 2 weeks (16.5, 95% CI 15.6 to 17.4) and 6 weeks (11.3, 95% CI 10.4 to 12.2) in the TUMT-alone group (P<0.0005). However, by the final evaluation at 12 weeks, no significant difference between the groups in mean IPSS was evident. A similar temporal pattern of difference between the two study groups was also observed in QOL score. No significant between-group difference in mean Qmax was evident after TUMT. Urinary retention 1 week or more in duration occurred in 5 (12%) of 40 TUMT-alone group patients compared with 1 (2%) of 41 TUMT plus tamsulosin group patients. CONCLUSIONS: Neoadjuvant and adjuvant alpha-blocker treatment results in significantly greater early symptom reduction and QOL score improvement after TUMT, adding to the clinical utility of this minimally invasive treatment modality. In addition, post-TUMT complications such as urinary retention may be reduced.     

Effect of two aspirin pretreatment regimens on niacin-induced cutaneous reactions

OBJECTIVE: To compare the effects of pretreatment with two aspirin regimens and placebo on niacin-induced cutaneous reactions. DESIGN: Randomized, double-blind, placebo-controlled, crossover study. SETTING: Internal medicine clinic in an academic health center. PARTICIPANTS: Forty-two healthy subjects (22 males and 20 females) between the ages of 35 and 65 (mean age 44.2 years) were recruited and completed the study. Subjects received aspirin 325 mg, aspirin 650 mg, and placebo for 4 consecutive days, and on the fourth day also ingested 500 mg of immediate-release niacin 30 minutes after taking aspirin or placebo. They reported the intensity of flushing, headache, pruritus, tingling, and warmth on a 10-cm visual analogue scale. Reactions were evaluated at time 0 (before the niacin dose), and at 15, 30, 60, and 120 minutes following the niacin dose. Cutaneous reactions were compared at each evaluation time and scored by two other methods. The peak intensity was the highest score recorded at any of the four evaluation times after niacin administration. An intensity-time factor was calculated by totaling the scores of each of the four evaluation times. MEASUREMENT AND MAIN RESULTS: The symptom scores for flushing, itching, tingling, and warmth were all significantly reduced by both aspirin regimens (p < .05 in all cases), although there were no significant differences between the 325-mg and 650-mg doses. The results were similar for each scoring method. CONCLUSIONS: An aspirin regimen of 325 mg is effective in suppressing niacin-induced cutaneous reactions. Increasing the dose to 650 mg does not provide additional benefit.     

Tamsulosin 0.4 mg once daily: tolerability in older and younger patients with lower urinary tract symptoms suggestive of benign prostatic obstruction (symptomatic BPH). The European Tamsulosin Study Group

OBJECTIVES: To compare the safety and tolerability of tamsulosin 0.4 mg once daily in younger (< 65 years) and older (> or = 65 years) patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO). METHODS: In a retrospective analysis of two European double-blind, randomized, placebo-controlled trials, safety was assessed in 574 younger or older patients treated with tamsulosin or placebo for 12 weeks. RESULTS: The incidence of adverse events, drug-related adverse events, serious adverse events and discontinuations due to adverse events was similar in older and younger tamsulosin-treated patients and was not significantly different from placebo. Although abnormal ejaculation was slightly more common in younger than older men receiving tamsulosin, the difference was not statistically significant from the placebo groups in both age groups. The incidence of adverse events possibly associated with vasodilation in tamsulosin-treated younger and older patients was 8.4 and 4.2%, respectively; these were comparable with the values for placebo-treated patients: 7.5 and 6%, respectively. Baseline systolic blood pressure was higher in older than younger patients, but there were minimal changes in blood pressure or pulse rate in tamsulosin- or placebo-treated patients in either age group. CONCLUSIONS: Tamsulosin is well tolerated and suitable for use in older and younger patients with LUTS suggestive of BPO (symptomatic BPH).     

Tamsulosin and chlormadinone for the treatment of benign prostatic hyperplasia. The Kobe University YM617 Study Group

The recent introduction of selective alpha-adrenoceptor blockers adds a further therapeutic option for the treatment of benign prostatic hyperplasia (BPH). Tamsulosin, a selective alpha 1-blocker, has proved effective in relieving irritative and obstructive symptoms caused by BPH. To investigate whether the combination of tamsulosin with the anti-androgenic drug chlormadinone is of further therapeutic benefit, 80 patients randomly received tamsulosin 0.2 mg daily, chlormadinone 50 mg daily or a combination of tamsulosin 0.2 mg and chlormadinone 50 mg daily for 16 weeks. Greater improvement in subjective symptoms of BPH was obtained with either tamsulosin alone or in combination with chlormadinone than with chlormadinone alone. However, the greatest improvement in objective uroflowmetric data was obtained with chlormadinone in combination with tamsulosin. Thus, the combination of tamsulosin with chlormadinone appears to be more beneficial than either of these agents used as monotherapy. Further investigation is required to fully evaluate the therapeutic effects of this combination. After the trial period one-third of the chlormadinone and tamsulosin/chlormadinone-treated patients needed no further treatment due to the satisfactory relief of symptoms. At 12 months follow-up, however, one-fourth of the patients had undergone transurethral resection of the prostate (TUR-P) regardless of medication. This suggests a limitation of the medical treatment of BPH.     

A prospective, randomized 1-year clinical trial comparing transurethral needle ablation to transurethral resection of the prostate for the treatment of symptomatic benign prostatic hyperplasia

PURPOSE: We assess the 1-year efficacy and safety of transurethral needle ablation of the prostate compared to transurethral resection of the prostate for the treatment of symptomatic benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: A prospective, randomized clinical trial of 121 men 50 years old or older with symptomatic BPH was performed at 7 medical centers across the United States. Of the men 65 (54%) were treated with transurethral needle ablation of the prostate and 56 (46%) underwent transurethral resection of the prostate. Mean and percentage changes from baseline and between cohorts for American Urological Association (AUA) symptom score, AUA bother score, quality of life score, peak urinary flow rate and post-void residual urine volume were measured at 1, 3, 6 and 12 months following treatment. Length of procedure, hospitalization, type of anesthesia, post-procedure catheterization, side effects and sexual function were compared. RESULTS: Transurethral needle ablation and resection resulted in a statistically significant improvement in AUA symptom, bother and quality of life scores, peak urinary flow rate and post-void residual. At 1-year followup, needle ablation and resection were equally effective in enhancing quality of life. Needle ablation had less effect on sexual function, with resection being associated with a greater incidence of retrograde ejaculation. Needle ablation could be performed as an outpatient procedure with local anesthesia while resection required anesthesia and hospitalization. Needle ablation was associated with markedly fewer side effects than resection. CONCLUSIONS: Compared to transurethral resection of the prostate, transurethral needle ablation of the prostate is an efficacious, minimally invasive treatment for symptomatic BPH that is associated with few side effects.     

A randomized, placebo-controlled dose-comparison trial of haloperidol for psychosis and disruptive behaviors in Alzheimer's disease

OBJECTIVE: The goal of this study was to compare the efficacy and side effects of two doses of haloperidol and placebo in the treatment of psychosis and disruptive behaviors in patients with Alzheimer's disease. METHOD: In a 6-week random-assignment, double-blind, placebo-controlled trial (phase A), haloperidol, 2-3 mg/day (standard dose), and haloperidol, 0.50-0.75 mg/day (low dose), were compared in 71 outpatients with Alzheimer's disease. For the subsequent 6-week double-blind crossover phase (phase B), patients taking standard- or low-dose haloperidol were switched to placebo, and patients taking placebo were randomly assigned to standard- or low-dose haloperidol. RESULTS: For the 60 patients who completed phase A, standard-dose haloperidol was efficacious and superior to both low-dose haloperidol and placebo for scores on the Brief Psychiatric Rating Scale psychosis factor and on psychomotor agitation. Response rates according to three sets of criteria were greater with the standard dose (55%-60%) than the low dose (25%-35%) and placebo (25%-30%). The advantage of standard dose over low dose was replicated in phase B. In phase A, extrapyramidal signs tended to be greater with the standard dose than in the other two conditions, primarily because of a subgroup (20%) who developed moderate to severe signs. Low-dose haloperidol did not differ from placebo on any measure of efficacy or side effects. CONCLUSIONS: The results indicated a favorable therapeutic profile for haloperidol in doses of 2-3 mg/day, although a subgroup developed moderate to severe extrapyramidal signs. A starting dose of 1 mg/day with gradual, upward dose titration is recommended. The narrow therapeutic window observed with haloperidol may also apply to other neuroleptics used in Alzheimer's disease patients with psychosis and disruptive behaviors.     

Initial and repeat screening for Chlamydia trachomatis during pregnancy

BACKGROUND: We examined the efficacy and safety of three different dosages of venlafaxine hydrochloride (75, 225, and 375 mg/day) in a multicenter, randomized, double-blind, placebo-controlled, four-group study. METHOD: Outpatients, 18 to 65 years old, who met DSM-III criteria for major depression were included (N = 358 randomized; 194 completed). Of the total patients completing the trial, 59%, 56%, 51%, and 51% were in the placebo, 75-mg, 225-mg, and 375-mg groups, respectively. The primary outcome measures were the Hamilton Rating Scale for Depression (HAM-D21) total, HAM-D21 depression item, Montgomery-Asberg Depression Rating Scale total, and Clinical Global Impressions scale. RESULTS: Each dosage of venlafaxine was associated with statistically significant improvement as compared with placebo, based on the intent-to-treat sample. The two higher dosages were associated with a modestly greater antidepressant response than was the 75-mg dosage. Nausea, dizziness, somnolence, and anorexia were the most common adverse events attributable to venlafaxine. Since headache occurred at a similar frequency in both the drug and placebo groups, we did not consider it to be attributable to venlafaxine use. Withdrawal from the study due to adverse events occurred in 5%, 17%, 24%, and 30% of the patients in the placebo, 75-mg, 225-mg, and 375-mg groups, respectively. CONCLUSION: Venlafaxine, at dosages of 75-375 mg/day, is an effective and well-tolerated antidepressant. With increasing dosage, greater efficacy and possibly more adverse effects will occur.     

Dependency scoring in a critical care area: a direct nursing assessment method

The urinary symptoms characteristic of benign prostatic hyperplasia (BPH) can have a considerable impact on patients' quality of life. Symptom score assessment is now used in BPH, although a number of different instruments are available. Controlled clinical trials with selective alpha 1 adrenoceptor antagonists such as doxazosin, prazosin and terazosin have shown these agents to be effective in the treatment of BPH. The effects of doxazosin on the severity and bothersomeness of BPH symptoms were determined in three multicentre, double-blind, placebo-controlled clinical studies, involving a total of 609 normotensive and hypertensive patients. Doxazosin was initiated at a dosage of 0.5 or 1 mg once daily, with a final dose range of up to 12 mg once daily. The duration of active treatment was 12 to 14 weeks. Significant improvements were seen in symptom severity and bothersomeness with doxazosin compared with placebo, in both patient populations. The onset of symptomatic improvement was rapid, occurring within two weeks of treatment initiation, and efficacy was sustained throughout the treatment period. A long-term, open label extension of these studies has demonstrated sustained efficacy during 48 months of follow-up. Since symptom relief is the primary goal of therapy in BPH, and since doxazosin's effects are rapid in onset and sustained in duration, it appears that doxazosin is an effective agent for the treatment of symptomatic BPH in both normotensive and hypertensive men.