The economic impact of using alfuzosin 10 mg once daily in the management of acute urinary retention in the UK: a 6-month analysis

OBJECTIVE: To calculate the economic consequences of using alfuzosin 10 mg once daily for managing acute urinary retention (AUR) related to benign prostatic hyperplasia (BPH). METHODS: We examined whether alfuzosin use during hospitalization for AUR and for 6 months after a successful trial without catheter (TWOC) is cost effective compared to placebo and immediate prostatectomy, from the perspective of patients managed in the National Health Service (NHS) in the UK. A decision-analysis model was developed to estimate the costs of various treatment options within the first 6 months after a first episode of AUR. Clinical data were obtained from a large randomized clinical trial comparing alfuzosin 10 mg with placebo, and from published reports. Cost data were obtained from both NHS and resource-use data gathered during the clinical trial. A Monte Carlo analysis, allowing variability in all uncertain variables of the model, was used to calculate the uncertainty surrounding the results. RESULTS: Treating patients with alfuzosin during initial hospitalization for AUR and in the first 6 months after a successful TWOC generates a cost-saving of pounds 349 relative to placebo. Savings related to immediate prostatectomy were pounds 892; both savings were significant (P < 0.05). Alfuzosin treatment was associated with a lower rate of prostatectomy after discharge from hospital after a successful TWOC. CONCLUSION: Treatment with alfuzosin 10 mg once daily before and after a successful TWOC has both clinical and economic benefits. It decreases the need for emergency surgery for BPH and reduces treatment costs in the first 6 months.     

阿芙唑嗪及多沙唑嗪十二指肠给药对猫尿道压的选择性作用(英文)

目的:观察不同给药途径对阿芙唑嗪(Alf)和多沙唑嗪(Dox)降尿道压的选择性作用,方法:电刺激麻醉猫腹下神经以升高尿道压。比较十二指肠和静脉两种途径给药时,Alf和Dox降低平均动脉血压(MBP)及尿道压(UP)的作用,结果:相同电刺激条件下(10 Hz,25 V),Alf肠道给药与静脉给药时ED_(20)(BP))/ED_(50)(UP))比值为10.9:4.3;Dox两种给药途径的比值为3.1:2.1,Alf十二指肠给药降尿道压作用的选择性优于静脉给药,Dox两种给药途径的作用无显著性差异,结论:Alf胃肠道给药时,选择性降低电刺激诱发的尿道压升高,而Dox无此特点,Alf对尿道的选择性作用与药物生物利用度和生物转化的种属差异无关。     

Semen analysis in chronic bacterial prostatitis： diagnostic and therapeutic implications

The significance and diagnostic value of semen analysis in chronic bacterial prostatitis has been extensively debated and remains controversial. To investigate the diagnostic relevance of semen culture in the bacteriological workup of prostatitis patients, we retrospectively analyzed a clinical database of 696 symptomatic patients. All patients were routinely subjected to a four-glass test, followed by semen culture and analysis. This allowed to dissect from the database three different diagnostic scenarios, and to compare the ＇two-glass＇ pre-/post- massage test and the standard ＇four-glass＇ test with a ＇five-glass＇ test （four-glass plus post-VB3 semen culture）. The ＇five-glass＇ test showed 3.6- or 6.5-fold increases in relative sensitivity and lesser reductions （-13.2% or -14.7%） in relative specificity for traditional uropathogens （TUs） compared with the four-glass or two-glass test, respectively. The area under the ROC curve and Jouden＇s index were increased, whereas positive and negative likelihood ratios were lower than comparators, indicating that the ＇five-glass＇ assay may be superior in confirming the negative outcome of both standard tests. The five-, four-, and two-glass tests detected TUs （Enterobacteriaceae, Enterococci, etc.） in 120, 33, and 20 patients and unusual pathogens （Streptococci, other Gram-positive species, Mycoplasmata, and others） in 130, 56, and 45 patients, respectively. When patients were subjected to pharmacological treatment, including a combination of a fluoroquinolone and a macrolide, no differences in eradication rates were observed between groups diagnosed with different tests, irrespective of pathogen category. Eradication was associated with long-term sign/symptom remission; no significant intergroup differences in sign/symptom scores were observed throughout a 24-month off-therapy follow-up period. In conclusion, our data support the usefulness of semen analysis in the diagnostic workup ofprostatitis patients when this test is used to complement the four-glass Meares and Stamey test. Improvement of microbiological assays conveys important diagnostic and therapeutic implications.     

Alfuzosin 10 mg once daily for treating benign prostatic hyperplasia: a 3-year experience in real-life practice

OBJECTIVES

To assess the 3‐year efficacy and safety of the selective α₁‐blocker alfuzosin at 10 mg once daily in men with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) in ‘real‐life practice’. The influence of treatment response on the risk of acute urinary retention (AUR) and BPH‐related surgery was also analysed.

PATIENTS AND METHODS

In all, 689 European men (mean age 67.6 years) were enrolled by general practitioners in a 3‐year open‐label study with alfuzosin at 10 mg once daily. They were asked to complete the International Prostate Symptom Score (IPSS), its eighth question (bother score), and the Danish Prostatic Symptom Score for sexual function (DAN‐PSSsex). Efficacy was analysed at the endpoint in the intent‐to‐treat population. The impact of baseline variables (age, PSA level, IPSS and bother severity) and dynamic variables (IPSS worsening of ≥4 points and bother at the last available assessment under treatment) on the risk of AUR and BPH‐related surgery was evaluated.

RESULTS

With alfuzosin, IPSS improved by 6.4 points (?33.4%) from baseline (P < 0.001), reaching ≥3 points and >6 points in 71.3% and 47.2% of men, respectively. There were also significant (P < 0.001) improvements from baseline in nocturia (?0.8, ?25.5%), bother score (?1.7, ?40.7%) and DAN‐PSSsex weighted scores with treatment. Symptom relief was rapid and maintained over 3 years. Overall, 78 men (12.4%) had an IPSS worsening of ≥4 points, 16 (2.6%) had AUR, and 36 (5.7%) required BPH‐related surgery. Symptom deterioration during treatment and high baseline PSA values were the best predictors of AUR and BPH‐related surgery. Alfuzosin was well tolerated, dizziness being the most frequent adverse event (4.5%) possibly related to vasodilatation. Ejaculatory disorders were uncommon (0.4%). Changes in blood pressure remained marginal, including in men aged ≥65 years and those receiving antihypertensive agents.

CONCLUSION

Alfuzosin administered for 3 years at 10 mg once daily in real‐life practice is effective and well tolerated. High PSA values and symptom worsening under treatment appear the best predictors of AUR and BPH‐related surgery in the long term. Treatment with alfuzosin might thus help to identify patients at risk of LUTS/BPH progression in order to optimize their management.     

3种新型α1-受体阻断剂的手性流动相HPLC分离与制备

目的建立3种新型α₁-受体阻断剂的手性流动相HPLC分离与半制备方法。方法通过探讨有机相、手性添加剂、流动相的pH、扫尾剂、反相固定相对手性分离的影响,选择最佳的手性分离条件。结果基线分离了3种新型α₁-受体阻断剂对映体,并制备了毫克级样品。结论所建立的分离与制备方法可用于该类新药的手性研究与开发。     

Management of acute urinary retention: a worldwide survey of 6074 men with benign prostatic hyperplasia

Study Type – Therapy (symptom prevalence) Level of Evidence 2a What's known on the subject? and What does the study add? Largest survey ever conducted evaluating the management of AUR in real life practice in a wide range of health care systems. It shows that urethral catheterization followed by a TWOC has become a standard worldwide and that α₁‐blockade prior to TWOC doubles the chances of success. It also evidences important differences (hospitalization rate, duration of catheterization ...) between countries/regions reflecting lack of guidelines. This large survey also clearly identifies predictors of TWOC failure.

OBJECTIVES

• ? To evaluate the management of acute urinary retention (AUR) associated with benign prostatic hyperplasia (BPH) in real‐life practice.
• ? To identify predictors of successful trial without catheter (TWOC).

MATERIALS AND METHODS

• ? In all, 6074 men catheterized for painful AUR were enrolled in a prospective, cross‐sectional survey conducted in public and private urology practices in France, Asia, Latin America, Algeria and the Middle East.
• ? Patient clinical characteristics, type of AUR and its management (type of catheterization, hospitalization, TWOC, use of α₁‐blockers, immediate or elective surgery) and adverse events observed during the catheterization period were recorded.
• ? Predictors of TWOC success were also analysed by multivariate regression analysis with stepwise procedure.

RESULTS

• ? Of the 6074 men, 4289 (71%) had a spontaneous AUR and 1785 (29%) had a precipitated AUR, mainly as the result of loco‐regional/general anaesthesia (28.5%) and excessive alcohol intake (18.2%).
• ? Presence of BPH was revealed by AUR in 44% of men. Hospitalization for AUR varied between countries, ranging from 1.7% in Algeria to 100% in France. A urethral catheter was inserted in most cases (89.8%) usually followed by a TWOC (78.0%) after a median of 5 days. Overall TWOC success rate was 61%.
• ? Most men (86%) received an α₁‐blocker (mainly alfuzosin) before catheter removal with consistently higher TWOC success rates, regardless of age and type of AUR. Multivariate regression analysis confirmed that α₁‐blocker before TWOC doubled the chances of success (odds ratio 1.92, 95% CI 1.52–2.42, P < 0.001).
• ? Age ≥70 years, prostate size ≥50 g, severe lower urinary tract symptoms, drained volume at catheterization ≥1000 mL and spontaneous AUR favoured TWOC failure. Catheterization >3 days did not influence TWOC success but was associated with increased morbidity and prolonged hospitalization for adverse events.
• ? In the case of TWOC failure, 49% of men were recatheterized and had BPH surgery and 43.5% tried another TWOC with a success rate of 29.5%. Elective surgery was preferred to immediate surgery.

CONCLUSIONS

• ? TWOC has become a standard practice worldwide for men with BPH and AUR.
• ? In most cases, an α₁‐blocker is prescribed before TWOC and significantly increases the chance of success.
• ? Prolonged catheterization is associated with an increased morbidity.

     

Combination of phosphodiesterase‐5 inhibitors and α‐blockers in patients with benign prostatic hyperplasia: treatments of lower urinary tract symptoms,erectile dysfunction,or both?

As the prevalence of both erectile dysfunction (ED) and lower urinary tract symptoms (LUTS) increases with age, physicians could be in the position to manage these two conditions simultaneously. Moreover, medical therapies for either one of these conditions can affect the other and this should be carefully considered when making treatment decisions. Pharmacotherapy for benign prostatic hyperplasia (BPH)/LUTS can cause side-effects affecting sexual function. Hence, 5alpha-reductase inhibitors such as finasteride and dutasteride are associated with a greater risk of ED, ejaculatory disorders (EjD) and decreased libido than is placebo. Among alpha1-adrenergic blockers, tamsulosin is associated with an increased risk of EjD. However, some alpha1-adrenergic blockers can also have a positive impact on erection. This is the case for alfuzosin, which has been shown to enhance erectile function in experimental models, probably by reducing the sympathetic tone and thus relaxing corpus cavernosum smooth muscle cells. Phosphodiesterase 5 (PDE-5) inhibitors are commonly used to treat ED. There is increasing evidence that they might also have a beneficial effect on LUTS, probably through the nitric-oxide pathway. Nitric oxide is an important mediator of the relaxation of isolated bladder and urethral smooth muscle, and could modulate prostatic smooth muscle tone. Alpha1-adrenergic blockers and PDE-5 inhibitors can therefore have a positive impact on both ED and LUTS. Although placebo-controlled studies are needed to confirm the impact of these drugs, alone or combined, on both ED and LUTS, this reinforces the need for a common approach to managing these two highly prevalent and bothersome conditions.     

Medical expulsive therapy using alfuzosin for patient presenting with ureteral stone less than 10 mm: A prospective randomized controlled trial

Objectives: To assess the spontaneous passage rate for patients being treated with alfuzosin 10 mg daily after presenting with an acute ureteral stone compared with a control group, and to assess the respective pain control status. Methods: This was a prospective randomized controlled trial. Patients presenting with an acute ureteral stone (size 5–10 mm) were enrolled and randomized into a medical expulsive therapy (MET) group or control group. The MET group received alfuzosin slow release (SR) 10 mg daily for 4 weeks and dologesic (paracetamol + dextropropoxyphene, four tablets daily on demand) for 2 weeks. The control group received the same analgesics for 2 weeks only. Diclofenac sodium SR 100 mg daily for 2 weeks was added in case of suboptimal pain control. All the patients were assessed through phone interview at week 2 and with kidney–ureter–bladder X‐ray at week 5 to check for any evidence of stone passage. Results: A total of 67 patients were included in the analysis. The overall spontaneous passage rate was increased by 31.8% with MET (P = 0.006). For an upper ureteral stone, the rate was increased by 51.3% (P = 0.01). The MET group used significantly less dicolofenac sodium (1.5 tablets vs 6.7 tablets, P = 0.031). Conclusions: MET using alfuzosin SR 10 mg daily is effective to enhance the ureteral stone spontaneous passage rate, particularly for upper ureteral stones. Fewer analgesic drugs are consumed and more patients can avoid ureteroscopic lithotripsy and/or extracorporeal shock wave lithotripsy.