Evaluation of the Clinical Benefit of Permixon and Tamsulosin in Severe BPH Patients—PERMAL Study Subset Analysis

Objective: To compare the efficacy of the lipido-sterolic extract of Serenoa repens, Permixon, to that of the α–blocker, tamsulosin, in the treatment of severe low urinary tract symptoms (LUTS) of benign prostatic hyperplasia (BPH).Methods: In a 12-month, double-blind, randomized study that showed equivalent efficacy of Permixon 320 mg/day and tamsulosin 0.4 mg/day (“PERMAL study”), 685 BPH patients with IPSS ≥10 had been analyzed for efficacy. Of these, the 124 patients with severe LUTS (IPSS >19) at randomization were retained for this subset analysis. After a 4-week run-in period, 59 and 65 patients had been randomized to tamsulosin and Permixon groups, respectively. Both treatment groups were compared regarding the evolution from baseline of total IPSS and its irritative and obstructive subscores, LUTS-related QoL, prostate volume, Q_max and MSF-4 (sexual activity questionnaire) at different time points over 1 year. An analysis of variance of changes from baseline to end point was performed for all the parameters. The over-time evolutions of total, irritative and obstructive IPSS were further compared using a variance analysis for repeated measurements.Results: At 12 months, total IPSS decreased by 7.8 with Permixon and 5.8 with tamsulosin (p=0.051); the irritative symptoms improved significantly more (p=0.049) with Permixon (−2.9 versus −1.9 with tamsulosin). The superiority of Permixon in reducing irritative symptoms appeared as soon as month 3 and was maintained up to month 12 (p=0.03).Conclusion: Permixon 320 mg/day was shown to be slightly superior to tamsulosin 0.4 mg/day in reducing LUTS in severe BPH patients after 3 months and up to 12 months of treatment.     

医院编制管理存在的问题与对策

医院的编制长期存在着总数过大，计划外用工日趋增多；学科间“缺编”与“超编”现象并存；年龄结构、技术结构不合理；机构膨胀，行政人员增长过速等，这些弊端阻碍了医院的建设与发展。解决医院编制管理中这些问题的基本思路是从实际出发，着眼未来，适应发展，精简高效。一是制定新的编制标准，重新核定编制数；二是建立多种约束机制；三是建立和完善合理的人才流动机制；四是精简职能机构，优化组合     

Updated meta-analysis of clinical trials of Serenoa repens extract in the treatment of symptomatic benign prostatic hyperplasia

OBJECTIVES: To determine, by analysing all available clinical trial data, the clinical efficacy against placebo of an extract from the fruit of the American dwarf palm tree, Serenoa repens (Permixon, Pierre Fabre Médicament, Castres, France), as there is controversy about the use of phytotherapeutic agents in men with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH). METHODS: All clinical trial data published on Permixon, comprising 14 randomized clinical trials and three open-label trials, involving 4280 patients, were analysed. These trials were of different size (22-1100 patients) and duration (21-720 days). The peak urinary flow rate and nocturia were the two common endpoints. The statistical analysis was based on a random-effects meta-analysis. RESULTS: Permixon was associated with a mean (sem) reduction in the International Prostate Symptom Score (IPSS) of 4.78 (0.41). The mean placebo effect on peak urinary flow rate was an increase of 1.20 (0.49) mL/s. The estimated effect of Permixon was a further increase of 1.02 (0.50) mL/s (P = 0.042). Placebo was associated with a reduction in the mean number of nocturnal voids of 0.63 (0.14); there was a further reduction attributable to Permixon of 0.38 (0.07) (P < 0.001). There was some heterogeneity among the studies for nocturia; one over 2 years involving 396 patients and showing no difference between placebo and Permixon had a large effect on the results. CONCLUSIONS: This meta-analysis of all available published trials of Permixon for treating men with BPH showed a significant improvement in peak flow rate and reduction in nocturia above placebo, and a 5-point reduction in the IPSS.     

伯泌松治疗良性前列腺增生症(附529例报告)

目的　观察伯泌松治疗良性前列腺增生症（ＢＰＨ） 的有效性与安全性。　方法　全国４５ 家医院５２９ 例ＢＰＨ 病人口服伯泌松３ 个月,用量为１６０ｍｇ ,每天二次。　结果　口服伯泌松３ 个月后,病人前列腺症状评分（ＩＰＳＳ） 减少３７ ．５ ％ ,评分减少≥３ 分者占８９ ．６ ％ ,最大尿流率从（１１ ．１ ±７ ．８）ｍｌ／ｓ 增加到（１４ ．９±７ ．８）ｍｌ／ｓ,最大尿流率改善≥３ｍｌ／ｓ 的病人占５６ ．５％ ;生活质量评分改善≥１分的病人占７８ ．４ ％ ,前列腺体积平均减少９ ．１ ％ ;性生活也有所改善,膀胱剩余尿量减少４３ ．５ ％ 。耐受性良好,服药过程中无血压下降。　结论　伯泌松治疗ＢＰＨ 安全、有效     

Comparison of the Effects of Hexanic Extract of Serenoa repens (Permixon) and Tamsulosin on Inflammatory Biomarkers in the Treatment of Benign Prostatic Hyperplasia-Related Lower Urinary Tract Symptoms

ContextChronic prostatic inflammation appears to have a key role in the pathogenesis and progression of benign prostatic hyperplasia (BPH). The PERMIN study compared the effects of hexanic extract of Serenoa repens (Permixon; Pierre Fabre, Castres, France) and tamsulosin on inflammation-related biomarkers secreted in urine of patients with BPH-related lower urinary tract symptoms (LUTS).ObjectiveTo review key features of the PERMIN study as they relate to treatment effects on the messenger RNA expression of selected inflammation-related genes and proteins.Evidence acquisitionThis article is based primarily on material presented at a satellite symposium entitled, “Inflammation and Prostatic Diseases: From Bench to Bedside,” held during the 2015 annual meeting of the European Association of Urology in Madrid, Spain. Current data regarding the link between inflammation and BPH were reviewed.Evidence synthesisPermixon showed a more pronounced effect than tamsulosin on selected inflammation-related genes and proteins. Among the 15 most frequently expressed genes in patients at baseline, 73% were favourably affected by Permixon versus 27% with tamsulosin, as indicated by the combination of downregulation and fewer upregulation effects. Expression of inflammatory proteins (CCL2/MCP-1, CXCL10/IP-10, macrophage migration inhibitory factor [MIF]) was downregulated in a higher percentage of patients and upregulated in a lower percentage of patients treated with Permixon compared with tamsulosin. In Permixon-treated patients, greater improvement in the International Prostate Symptom Score was observed at 3 months in those who overexpressed MIF protein at baseline compared with those who did not (−6.4 vs −4.5).ConclusionsDownregulation of inflammation-related genes and proteins by Permixon brought meaningful symptomatic improvement in patients with moderate to severe LUTS. Patients with high chronic prostatic inflammation may benefit from early treatment with Permixon.Patient summaryDownregulation of inflammation-related genes and proteins by Serenoa repens (Permixon) was associated with meaningful symptomatic improvement in patients with moderate to severe lower urinary tract symptoms. Patients with high chronic prostatic inflammation may benefit from early treatment with Permixon.     

Serenoa repens extract targets mitochondria and activates the intrinsic apoptotic pathway in human prostate cancer cells

OBJECTIVE

To investigate the effects of Serenoa repens extract (Sr) in human PC3 and LNCaP prostate cancer and MCF7 breast cancer cells, with specific emphasis on the role of the mitochondrial apoptotic pathway, as the molecular pathway through which Sr, a natural product of plant origin, induces death of prostate cancer cells in culture is still unknown.

MATERIAL AND METHODS

Cellular and mitochondrial structure and function, and the cell cycle, were analysed using light, electron and fluorescence microscopy, spectrophotometry and flow cytometry. Apoptosis was evaluated using biochemical and cytohistochemical methods.

RESULTS

Cells treated with Sr underwent massive vacuolization and cytosolic condensation, followed by cell death only in the prostate lines. Within minutes of adding Sr to prostate cells, it caused opening of the permeability transition pore (PTP), which led to complete mitochondrial depolarization within 2 h, and to the appearance of small, pycnotic mitochondria. Release of cytochrome c and SMAC/Diablo to the cytosol was detectable after 4 h of treatment, while caspase 9 activation and poly(ADP‐ribose) polymerase 1 cleavage occurred at 16 h, followed by appearance of a sub‐G1 peak and apoptosis at 24 h.

CONCLUSION

Sr selectively induces apoptotic cell death of prostate cancer cells through the intrinsic pathway, and activation of the mitochondrial PTP might play a central role in this process.     

Reproducibility and Clinical and Concurrent Validity of the MSF-4: A Four-Item Male Sexual Function Questionnaire for Patients with Benign Prostatic Hyperplasia

Introduction: The MSF-4 (Male Sexual Function 4-item) questionnaire is a condition-specific four-item scale of men's sexuality. We describe two studies that were conducted to assess the reproducibility and validity of the MSF-4 questionnaire.
Methods: Study 1 was a Phase III, multicenter study with a double-blind, parallel group design which was conducted in five countries. The objectives were to check the construct validity and factorial structure of the MSF-4, along with internal consistency reliability and clinical validity. Study 2 was a longitudinal, noncomparative, observational multicenter study to assess the reproducibility and the clinical and concurrent validity of the MSF-4.
Results: When exploratory factor analysis was performed with a free number of factors, the variability of the global MSF-4 score was based on a single factor across all countries in Study 1 except Spain. There was a high level of internal consistency reliability (Cronbach's alphas 0.68–0.90) and the MSF-4 was able to significantly discriminate different health states as assessed by the International Prostate Symptom Score (I-PSS) or Quality of Life (QoL) questionnaire. In study 2, there was a significant correlation between the MSF-4 and the International Index of Erectile Function (IIEF) scores ( p = .0001 for all items) especially erectile function (correlation coefficient −0.77). The MSF-4 was able to distinguish among patients with differing degrees of benign prostatic hyperplasia (BPH) symptoms as measured by the I -PSS ( p = .0001) and between those with and without sexual disorders ( p = .0001).
Conclusion: The MSF-4 is a psychometrically validated questionnaire with good reproducibility and clinical validity, which allows easy and appropriate assessment of male sexual function in the clinical setting.