Christer Dahlstrand

A combined analysis of double‐blind trials of the efficacy and tolerability of doxazosin‐gastrointestinal therapeutic system, doxazosin standard and placebo in patients with benign prostatic hyperplasia

Objective To report an integrated analysis of two previous studies fully characterizing the clinical utility of the controlled‐release gastrointestinal therapeutic system (GITS) formulation of doxazosin in the treatment of benign prostatic hyperplasia (BPH).

Transurethral microwave thermotherapy versus transurethral resection for benign prostatic hyperplasia: preliminary results of a randomized study.

The results of transurethral microwave thermotherapy (TUMT) were compared in a prospective randomized study with those of transurethral resection (TURP) in patients with benign prostatic obstruction. In this preliminary report, 39 and 40 patients treated with TUMT and TURP, respectively, were followed between 2 and 12 months. Statistically significant improvements in symptom score, maximum flow rate, residual urine and maximum bladder capacity at cystometry were observed in both groups. The improvements were more pronounced in the TURP group, but major complications were more frequent in this group. Results are compared to other published studies.

Relationship Between Age, Prostate Volume, Prostate-specific Antigen, Symptom Score and Uroflowmetry in Men with Lower Urinary Tract Symptoms

Objectives: To estimate the relationship between age and the values of different diagnostic tests in men with lower urinary tract symptoms (LUTS) suggestive of benign prostatic enlargement (BPE) and to compare prostate growth curves between the normal population sample, healthy men and men with LUTS. Material and Methods: A series of 354 men (mean age 70.2 years; range 45-91 years) with LUTS due to BPE were stratified into seven age groups and reviewed retrospectively. All patients underwent a standard evaluation, involving determination of the International Prostate Symptom Score (IPSS), digital rectal examination, uroflowmetry, determination of the prostate-specific antigen (PSA) level and transrectal ultrasonography. Descriptive statistics were used to describe all the variables and Spearmans correlation test was used to evaluate the relationships between them. Results: The mean prostate volume was 40.1 (±23.9) cm[Formula: See Text] and mean PSA concentration 3.9 (±4.2) ng/ml. Both values increased progressively from 27.5 ml and 1.5 ng/ml, respectively in the <54 years age group to 48.2 ml and 5.4 ng/ml, respectively in the <80 years age group. However, in the 75-79 years age group there was a decrease in both prostate volume and symptom score; PSA concentration remained unchanged and maximal flow rate increased slightly. A statistically significant but weak correlation was found between prostate volume and age (r = 0.25, p < 0.0001) and between PSA and age (r = 0.28, p < 0.0001). Prostate volume correlated positively with serum PSA (r = 0.54, p < 0.0001). The correlations between maximum flow rate and age, prostate volume, PSA and IPSS were r = −0.21, p < 0.0001; r = −0.18, p < 0.0006; r = −0.29, p < 0.0001; and r = 0.14, p < 0.0098, respectively. Conclusions: These data confirm that prostate volume and serum PSA concentration are significantly correlated and increase with advanced age. The correlations between uroflowmetry (Qmax) and age, prostate volume, serum PSA and IPSS were also significant. However, there was no relationship between symptoms and objective measures of BPE. The increase in different parameters of the severity of benign prostatic hyperplasia with advanced age is not continuous. The prostate volume alone is not useful in the estimation of disease severity.

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 α1–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.

Invasive Urodynamic Studies are Well Tolerated by the Patients and Associated with a Low Risk of Urinary Tract Infection

Objective: An essential part of investigation of the lower urinary tract is pressure/flow studies (pQS). In fact, pQS is the only way of diagnosing bladder outlet obstruction. There is controversy regarding whether or not prophylactic antibiotic treatment is necessary. This prospective study was carried out in order to determine the frequency of infections and/or distress after pQS performed without the use of antibiotic prophylaxis. Material and Methods: One hundred and twenty-three patients were included in the present study, all males. They were requested to answer a questionnaire 1 week after pQS. Questions were asked concerning symptoms of voiding disorders, dysuria, hematuria, incidence of fever and the patients acceptance of the investigation after the pQS procedure. Urine was obtained for culture immediately before the investigation and 3 and 7 days after the pQS. Results: Forty-six per cent of the patients experienced some degree of transient dysuria after pQS, and 18.5% experienced voiding problems of varying nature. Five per cent of the patients had hematuria and 2.5% reported fever. Fifty per cent of the patients experienced some degree of discomfort during the pQS investigation, and 4.1% had positive culture and symptoms of UTI requiring antibiotic treatment. Conclusions: PQS is well accepted by the patients and the regular use of propylactic antibiotics is not indicated. We recommend, though, that patients at risk for serious complications from infections (e.g. those with prosthetic heart valves) should receive prophylactic antibiotics.OBJECTIVE An essential part of investigation of the lower urinary tract is pressure/flow studies (pQS). In fact, pQS is the only way of diagnosing bladder outlet obstruction. There is controversy regarding whether or not prophylactic antibiotic treatment is necessary. This prospective study was carried out in order to determine the frequency of infections and/or distress after pQS performed without the use of antibiotic prophylaxis. MATERIAL AND METHODS One hundred and twenty-three patients were included in the present study, all males. They were requested to answer a questionnaire I week after pQS. Questions were asked concerning symptoms of voiding disorders, dysuria, hematuria, incidence of fever and the patients acceptance of the investigation after the pQS procedure. Urine was obtained for culture immediately before the investigation and 3 and 7 days after the pQS. RESULTS Forty-six per cent of the patients experienced some degree of transient dysuria after pQS. and 18.5% experienced voiding problems of varying nature. Five per cent of the patients had hematuria and 2.5% reported fever. Fifty per cent of the patients experienced some degree of discomfort during the pQS investigation, and 4.1% had positive culture and symptoms of UTI requiring antibiotic treatment. CONCLUSIONS PQS is well accepted by the patients and the regular use of propylactic antibiotics is not indicated. We recommend, though, that patients at risk for serious complications from infections (e.g. those with prosthetic heart valves) should receive prophylactic antibiotics.

Continent cutaneous urinary diversion in patients with spinal cord injury

Study design:Retrospective study.Objective:To examine the functional results and effect on quality of life of continent cutaneous urinary diversion in spinal cord injured patients.Setting:Department of Urology, Sahlgrenska University Hospital, Göteborg, Sweden.Subjects:A total of 10 patients with spinal cord injury (SCI).Method:The patients were operated on with an ileal reservoir (Kock reservoir or T-pouch), Cr-EDTA clearance was determined preoperatively and at follow-up. The patients answered a questionnaire concerning reservoir function, various activities and quality of life. The patient charts were reviewed.Results:One patient died of pulmonary embolism 3 years after surgery. Two patients were reoperated on for reservoir perforation. All patients were satisfied/very satisfied with their reservoirs. Half of them reported improved ability to perform various activities. Eight out of nine patients reported improved quality of life.Conclusion:For a selected group of patients with SCI, continent cutaneous urinary diversion provides successful outcome with improved quality of life.

Home uroflowmetry: Improved accuracy in outflow assessment

To study home uroflowmetry and to compare this method to free or “traditional” uroflowmetry in the evaluation of the patient with symptomatic benign prostatic hyperplasia (BPH), and the relationship between the values of home uroflowmetry parameters and bladder outlet obstruction (BOO). Twenty‐five patients (mean age, 67 years) with symptomatic BPH were examined with home uroflowmetry, free uroflowmetry, and pressure‐flow measurement. The patients were assessed using the International Prostate Symptom score; digital rectal examination; routine blood chemistry, including serum prostate‐specific antigen level; urinanalysis; transrectal ultrasonography; and post‐void residual urine. The 24 hr were divided into “active time” (AT) and “sleep time” (ST). AT home uroflowmetry parameters were compared to ST ones. The home uroflowmetry parameters were compared to respective ones of the free uroflowmetry as well and those obtained by pressure‐flow measurement. The patients were asked about their opinion of home uroflowmetry. Home uroflowmetry was found to be a simpler and more acceptable method than free uroflowmetry. The mean Qmax of AT was significantly greater than the mean Qmax of ST, but the mean voided volume and mean voiding time of ST were significantly larger than those of AT. There was a close relationship between the mean Qmax at home and the Qmax in hospital, but the voided volume and voiding time measured in hospital were significantly larger than those at home. Home uroflowmetry provided an estimation of BOO for 46% of the patients as low if the home mean Qmax was >14 ml/sec, and as high if the home mean Qmax was <10 ml/sec. Home uroflowmetry was well accepted by the patients and gave more information than free uroflowmetry. In 46% of the cases, an estimation of BOO was obtained with home uroflowmetry. Neurourol. Urodynam. 18:25–32, 1999.

The Use of Biodegradable PGA Stents to Judge the Risk of Post-TURP Incontinence in Patients with Combined Bladder Outlet Obstruction and Overactive Bladder

OBJECTIVE For patients with the combination of severe bladder outlet obstruction (BOO) and severe overactive bladder (OB), no straightforward and safe treatment exists due to the risk of urge incontinence after TURP. In this study we have used a biodegradable polyglycolic stent to simulate the status after TURP and register the risk for urge incontinence. METHODS A total of 37 patients with severe OB, combined with moderate to severe BOO, were asked if they wanted to participate. Under cystoscopic vision a polyglycolic biodegradable stent was inserted in the prostatic urethra. RESULTS Twenty-five of the patients noticed no or only minor leakage and 19 of these have been subjected to TURP with good results. Three patients are on the waiting-list for TURP. Twelve of 37 patients were found to have major leakage after stent insertion. During the stent period, we noted five cases of complications, due to UTI, stent crash and irritation. All of these patients recovered within three weeks. CONCLUSIONS A biodegradable PGA stent seems to be a new and unique tool to test the risk for post-TURP incontinence in patients with combined BOO and severe OB.

A Cost-Effectiveness Analysis of Transurethral Resection of the Prostate and Transurethral Microwave Thermotherapy for Treatment of Benign Prostatic Hyperplasia : Two-Year Follow-up

OBJECTIVE To compare costs of transurethral prostatic resection (TURP) and transurethral microwave thermotherapy (TUMT) for symptomatic benign prostatic hyperplasia (BPH) in a randomized, controlled trial. METHODS In 70 BPH patients all costs were calculated for management, including complications and repeat treatment, during TURP or TUMT and 24-month follow-up. Clinical outcome was judged from Madsen-Iversen symptom score, peak urinary flow and residual urine. The effect of changes in some critical variables was assessed by sensitivity analysis. A cost-effectiveness analysis was carried out to compare the two methods. RESULTS Symptom reduction after 2 years was 92% in the TURP group and 83% in the TUMT group. The total costs over 2 years were SEK 24,234 and 14,830 in the respective groups. Costs for retreatments were higher after TUMT, while complication costs were higher in the TURP group. TUMT costs depend on the investment for the equipment, including disposable probes, and the degree of its utilization. TUMT was more cost-effective than TURP in relieving BPH-related symptoms during the 2-year follow-up. CONCLUSIONS Primary treatment costs were lower for TUMT than for TURP. Complication costs were higher in the trials TURP arm, while retreatment costs were greater in the TUMT arm. TUMT costs depend on investment in and utilization of the equipment and reuse of treatment probes. TUMT was more cost-effective than TURP in the 2-year study period.

Continent cutaneous urinary diversion is still a valid alternative after cystectomy for bladder carcinoma

Objective. We compared patient opinions concerning reservoir/bladder function as well as quality of life (QOL) after cystectomy for bladder carcinoma and continent cutaneous urinary diversion or orthotopic bladder reconstruction. Material and methods. Fifteen patients with Kock reservoirs (11 females, 4 males) and 11 men with orthotopic bladders answered the European Organization for Research and Treatment of Cancer quality-of-life questionnaire-C30 as well as specially constructed questions concerning reservoir/bladder function. The glomerular filtration rate (GFR) was determined using Cr–EDTA or iohexol clearance. Results. Functioning and global health/QOL scales did not differ between the two groups of operated patients or between diverted patients and gender- and age-matched groups from the general population. The majority of the patients were satisfied/very satisfied with their diversion but more patients were troubled by leakage in the orthotopic bladder group than in the Kock reservoir group. The GFR was similar in the two groups. Conclusion. Continent cutaneous urinary diversion is associated with fewer leakage problems than orthotopic bladder reconstruction after cystectomy for bladder carcinoma.