α-Blocker and Risk of Dementia in Patients with Benign Prostatic Hyperplasia: A Nationwide Population Based Study Using the National Health Insurance Service Database.

PURPOSE: A recent study demonstrated that tamsulosin increased the risk of dementia in patients with benign prostatic hyperplasia. However, this study had a number of limitations. We evaluated the association between α-blockers and dementia in patients with benign prostatic hyperplasia. MATERIALS AND METHODS: From the National Health Insurance Service database we collected and analyzed data on α-blockers and dementia in the entire Korean adult population with benign prostatic hyperplasia between January 2011 and December 2011. These patients were followed until September 2017. We tested the effect of α-blockers on the risk of dementia using propensity score matched Cox proportional hazard regression models and Kaplan-Meier survival analysis. RESULTS: During a mean ± SD followup of 1,580 ± 674.3 days all study inclusion and exclusion criteria were met by 59,263 patients with benign prostatic hyperplasia. In the unadjusted cohort the incidence of dementia in the tamsulosin, doxazosin, terazosin, alfuzosin and no medication cohorts were 17.97%, 18.55%, 20.64%, 17.62% and 22.60%, respectively. After propensity score matching the risk of dementia did not significantly differ in the tamsulosin cohort vs the doxazosin and alfuzosin cohorts (HR 1.038, 95% CI 0.960-1.121 and HR 1.008, 95% CI 0.925-1.098), respectively. Compared to the tamsulosin cohort the terazosin cohort had a higher risk of dementia (HR 1.112, 95% CI 1.052-1.196). However, the risk of dementia was significantly lower in the terazosin cohort than in the no medication cohort. CONCLUSIONS: The study findings indicate that benign prostatic hyperplasia medication is not associated with a risk of dementia by duration of use or by type.

Naftopidil for the treatment of lower urinary tract symptoms compatible with benign prostatic hyperplasia.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a common condition in ageing men that may cause lower urinary tract symptoms (LUTS). Treatment aims are to relieve symptoms and prevent disease-related complications. Naftopidil is an alpha-blocker (AB) that has a high affinity for the A1d receptor that may have advantages in treating LUTS in this setting. This is an update of a Cochrane Review first published in 2009. Since that time, several large randomised controlled trials (RCTs) have been reported, making this update relevant. OBJECTIVES: To evaluate the effects of naftopidil for the treatment of LUTS associated with BPH. SEARCH METHODS: We performed a comprehensive search using multiple databases (the Cochrane Library, MEDLINE, Embase, Scopus, LILAC, and Web of Science), trials registries, other sources of grey literature, and conference proceedings with no restrictions on the language of publication or publication status up to 31 May 2018 SELECTION CRITERIA: We included all parallel RCTs. We also included cross-over design trials. DATA COLLECTION AND ANALYSIS: Two review authors independently classified and abstracted data from the included studies. We performed statistical analyses using a random-effects model and interpreted them according to the Cochrane Handbook for Systematic Reviews of Interventions. Primary outcomes were urological symptom scores, quality of life (QoL) and treatment withdrawals for any reason; secondary outcomes were treatment withdrawals due to adverse events, acute urinary retention, surgical intervention for BPH, and cardiovascular and sexual adverse events. We considered outcomes measured up to 12 months after randomisation as short term, and later than 12 months as long term. We rated the certainty of the evidence according to the GRADE approach. MAIN RESULTS: We included 22 RCTs with 2223 randomised participants across four comparisons for short-term follow-up. This abstract focuses on only two of four comparisons for which we found data since two comparators (i.e. propiverine and Eviprostat (phytotherapy)) are rarely used. One study comparing naftopidil to placebo did not report any relevant outcomes and was therefore excluded. There were no trials that compared to combination therapy with naftopidil or any 5-alpha reductase inhibitors (5-ARIs) to combination therapy with other ABs and any 5-ARIs.All included studies were conducted in Asian countries. Study duration ranged from four to 12 weeks. Mean age was 67.8 years, prostate volume was 35.4 mL, and International Prostate Symptom Score was 18.3. We were unable to perform any of the preplanned subgroup analyses based on age and baseline symptom score.Naftopidil versus tamsulosinBased on 12 studies with 965 randomised participants, naftopidil may have resulted in little or no difference in urological symptom score (mean difference (MD) 0.47, 95% confidence interval (CI) -0.09 to 1.04 measured on a scale from 0 to 35 with higher score representing increased symptoms), QoL (MD 0.11, 95% CI -0.09 to 0.30; measured on a scale from 0 to 6 with higher scores representing worse QoL), and treatment withdrawals for any reason (risk ratio (RR) 0.92, 95% CI 0.64 to 1.34; corresponding to 7 fewer per 1000 participants, 95% CI 32 fewer to 31 more). Naftopidil may have resulted in little to no difference in sexual adverse events (RR 0.54, 95% CI 0.24 to 1.22); this would result in 26 fewer sexual adverse events per 1000 participants (95% CI 43 fewer to 13 more). We rated the certainty of evidence as moderate for urological symptom score and low for the other outcomes.Naftopidil versus silodosinBased on five studies with 652 randomised participants, naftopidil may have resulted in little or no difference in the urological symptom scores (MD 1.04, 95% CI -0.78 to 2.85), QoL (MD 0.21, 95% CI -0.23 to 0.66), and treatment withdrawals for any reason (RR 0.80, 95% CI 0.52 to 1.23; corresponding to 26 fewer per 1000 participants, 95% CI 62 fewer to 32 more). We rated the certainty of evidence as low for all these outcomes. Naftopidil likely reduced sexual adverse events (RR 0.15, 95% CI 0.06 to 0.42; corresponding to 126 fewer sexual adverse events per 1000 participants, 95% CI 139 fewer to 86 fewer). We rated the certainty of evidence as moderate for sexual adverse events. AUTHORS' CONCLUSIONS: Naftopidil appears to have similar effects in the urological symptom scores and QoL compared to tamsulosin and silodosin. Naftopidil has similar sexual adverse events compared to tamsulosin but has fewer compared to silodosin.

Urologists' attitudes to sexual complications of LUTS/BPH treatments.

INTRODUCTION: Many LUTS/BPH treatments currently available may affect sexual function (SD). We wished to assess urologists' attitude and practice in this area. METHODS: Attendees of an international meeting were randomly selected, interviewed and stratified by professional status and LUTS/BPH cases seen per month. There were four questions: treatment options offered, frequency of discussing erectile dysfunction (ED) with each treatment, frequency of discussing ejaculatory dysfunction (EjD) with each treatment, and offering alternative treatment based on the risks of sexual dysfunction. RESULTS: 199 of the 245 interviewed (81%) were urologists. The most common treatments offered were α-blockers (99.5%), 5-ARI (95.0%) and TURP (92.5%). About 70% of the specialists discuss ED before α-blockers (not known to cause ED). Regarding EjD, 70% discuss this prior to prescribing α-blockers, 60% before 5-ARI therapy, while 80% before TURP. A significant minority fails to discuss this complication in all areas. Many respondents do not routinely discuss alternative therapies on the risk of SD. The higher the caseload, the less likely was a urologist to offer alternative therapies, with 37% of urologists seeing over 30 LUTS/BPH patients per month stating they would "Not at all often" offer alternative therapies for this reason. CONCLUSIONS: There is a significant discrepancy in attitudes to counselling patients on SD related to LUTS/BPH treatments. This may, in some cases, affect the validity of consent to the treatment. Most urologists do not discuss alternative treatments with patients based on the risks of different outcomes and complications, and this seems more marked in those with the busier practices. This may sit ill with the concept of personalised healthcare.

Network Meta-Analysis of the Efficacy of Acupuncture, Alpha-blockers and Antibiotics on Chronic Prostatitis/Chronic Pelvic Pain Syndrome.

Alpha-blockers and antibiotics are most commonly used to treat chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) in clinical practice. Currently, increasing evidence also suggests acupuncture as an effective strategy. This network meta-analysis intended to assess the comparative efficacy and safety of acupuncture, alpha-blockers and antibiotics for CP/CPPS. Twelve trials involving 1203 participants were included. Based on decreases in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score, a network meta-analysis indicated that electro-acupuncture (standard mean difference [SMD]: 4.29; 95% credible interval [CrI], 1.96-6.65), acupuncture (SMD: 3.69; 95% CrI, 0.27-7.17), alpha-blockers (SMD: 1.85; 95% CrI, 1.07-2.64), antibiotics (SMD: 2.66; 95% CrI, 1.57-3.76), and dual therapy (SMD: 3.20; 95% CrI, 1.95-4.42) are superior to placebo in decreasing this score. Additionally, electro-acupuncture (SMD: 2.44; 95% CrI, 0.08-4.83) and dual therapy (SMD: 1.35; 95% CrI, 0.07-2.62) were more effective than alpha-blockers in decreasing the total NIH-CPSI total score. Other network meta-analyses did not show significant differences between interventions other placebo. The incidence of adverse events of acupuncture was relatively rare (5.4%) compared with placebo (17.1%), alpha-blockers (24.9%), antibiotics (31%) and dual therapy (48.6%). Overall, rank tests and safety analyses indicate that electro-acupuncture/acupuncture may be recommended for the treatment of CP/CPPS.

5-Alpha Reductase Inhibitors and the Risk of Prostate Cancer Mortality in Men Treated for Benign Prostatic Hyperplasia.

OBJECTIVE: To compare the risk of prostate cancer mortality among men treated with 5- alpha reductase inhibitors (5-ARIs) with those treated with alpha-adrenergic blockers (ABs) in community practice settings. PATIENTS AND METHODS: A retrospective matched cohort (N=174,895) and nested case-control study (N=18,311) were conducted in 4 regions of an integrated health care system. Men 50 years and older who initiated pharmaceutical treatment for benign prostatic hyperplasia between January 1, 1992, and December 31, 2007, and had at least 3 consecutive prescriptions were followed through December 31, 2010. Adjusted subdistribution hazard ratios, accounting for competing risks of death, and matched odds ratios were used to estimate prostate cancer mortality associated with 5-ARI use (with or without concomitant ABs) as compared with AB use. RESULTS: In the cohort study, 1,053 men died of prostate cancer (mean follow-up, 3 years), 15% among 5-ARI users (N= 25,388) and 85% among AB users (N=149,507) (unadjusted mortality rate ratio, 0.80). After accounting for competing risks, it was found that 5-ARI use was not associated with prostate cancer mortality when compared with AB use (adjusted subdistribution hazard ratio, 0.85; 95% CI, 0.72-1.01). Similar results were observed in the case-control study (adjusted matched odds ratio, 0.95; 95% CI, 0.78-1.17). CONCLUSION: Among men being pharmaceutically treated for benign prostatic hyperplasia, 5-ARI use was not associated with an increased risk of prostate cancer-specific mortality when compared with AB use. The increased prevalence of high-grade lesions at the time of diagnosis noted in our study and the chemoprevention trials may not result in increased prostate cancer mortality.

[Pharmacological treatment of benign prostatic hyperplasia]. / Medikamentöse Therapie des benignen Prostatasyndroms.

The pharmacological treatment of benign prostatic hyperplasia (BPH) is indicated when men suffer from lower urinary tract symptoms (LUTS) but there are no absolute indications for prostate surgery or severe bladder outlet obstruction. Phytotherapy can be used in men with mild to moderate LUTS and alpha-blockers can quickly and effectively decrease the LUTS and symptomatic disease progression. Phosphodiesterase type 5 inhibitors (PDE5-I) are an alternative to alpha-blockers when men experience bothersome side effects from alpha-blockers or erectile dysfunction. If patients predominantly have bladder storage symptoms and a small prostate, muscarinic receptor antagonists are a viable treatment option. The combination of alpha-blocker plus muscarinic receptor antagonist is more efficacious in reducing LUTS than the single drugs alone. The 5 alpha-reductase inhibitors (5ARI) can significantly decrease LUTS and disease progression (e.g. acute urinary retention and need for prostate surgery) in men with larger prostates (> 30-40 ml). The combination of 5ARI plus alpha-blocker can reduce LUTS and disease progression more effectively than drug monotherapy. Combination therapy with PDE5-I (tadalafil) plus 5ARI (finasteride) reduces LUTS more substantially than 5ARI alone and, additionally, PDE5-Is reduce the sexual side effects during 5ARI treatment.

[Negative effects on sexual function of medications for the treatment of lower urinary tract symptoms related to benign prostatic hyperplasia]. / Effets négatifs sur la sexualité des traitements médicamenteux des symptômes du bas appareil urinaire liés a l'hypertrophie bénigne de la prostate.

PURPOSE: The aim of this review is to discuss the negative effects on sexual function of medications for lower urinary tract symptoms secondary to benign prostatic hyperplasia (LUTS-BPH). METHODS: An international non-systematic literature review was performed. It included randomized trials of seven drugs of interest and the summaries of the characteristics of these products. This work did not aim comparison between the drugs. RESULTS: Only maximal reported frequencies are presented in this abstract. With prolonged-release alfuzosin, they were 2.8% vs. 1.3% for erectile dysfunction, compared to placebo and 1% vs. 0% for ejaculatory dysfunction. With doxazosin, the incidence was 5.8% vs. 3.3% for erectile dysfunction, 3.6% vs. 1.9% for reduced libido and 0.4% vs. 1.4% for ejaculatory disorders. The incidence of ejaculatory disorders with tamsulosin, was 11% vs. <1% with the placebo and with silodosin, it was 28.1% vs. 1.1%. With finasteride, at 12 months, the highest frequency was 9% vs. 5% for erectile dysfunction, 4.4% vs. 1.5% for ejaculatory disorders and 6.4% vs. 3.4% for reduced libido. At 24 months, for dutatsteride, frequencies were 7.3% vs. 4.0% for erectile dysfunction, 2.2% vs. 0.8% for ejaculatory disorders and 4.2% vs. 2.1% for reduced libido. For tadalafil, a phosphodiesterase-5 inhibitor, and tolerodine, an anticholinergic drug, no negative effect on ejaculation or libido has been reported. For plant extracts, no sexual adverse effects (AEs) were reported among the most common AEs. CONCLUSION: The medications for LUTS-BPH may alter erection, ejaculation or libido. A greater knowledge of the adverse effects of each of these drugs could guide physicians in the clinical management of men with BPH-LUTS.

Real-world use of Permixon® in benign prostatic hyperplasia--determining appropriate monotherapy and combination treatment.

INTRODUCTION: Benign prostatic hyperplasia (BPH) is a major health concern for aging men. The resulting lower urinary tract symptoms may have a profound effect on a patient's quality of life and it is recognized that patient acceptability of treatment is key to decreasing the human and economic burden of the condition. Alphaadrenergic antagonists (alpha-blockers), 5-alphareductase inhibitors (5-ARIs), and phytotherapy as monotherapy or in combination, form the mainstay of medical treatment. METHODS: The Adelphi Permixon Study, a cross-sectional study of representative consulting patients with BPH in two European countries, was undertaken to examine the reasons for choice of medication. Physicians completed patient record forms, and data were analyzed for clinical outcomes and their relationship with the choice of appropriate therapy. RESULTS: Patients receiving combination therapies for BPH are likely to be older and are more likely to be retired than those on monotherapy. Combination therapy is adopted in the real-world setting as first-line therapy on a not-infrequent basis. The analyses demonstrated an association between choice of Permixon® (Pierre Fabre Medicament, Castres, France) as appropriate monotherapy or in combination with alpha-blockers, and the following: BPH severity; treatment of general urinary symptoms, including storage and voiding symptoms; improvement of urinary flow rate; lack of a risk of sexual problems; and reduction of inflammation. Permixon combination with an alpha-blocker is associated with benefits in terms of speed of onset of action, reduction of inflammation, and a positive benefit regarding sexual problems when compared with use of alpha-blocker monotherapy. CONCLUSION: In the real clinical world, Permixon is considered an appropriate treatment for BPH as both monotherapy and in combination with alpha-blockers. Prescribing Permixon in combination with alpha-blockers can be demonstrated to provide benefits beyond use of either therapy alone.

Activated cranial cervical cord neurons affect left ventricular infarct size and the potential for sudden cardiac death.

To evaluate whether cervical spinal neurons can influence cardiac indices and myocyte viability in the acutely ischemic heart, the hearts of anesthetized rabbits subjected to 30 min of LAD coronary arterial occlusion (CAO) were studied 3h after reperfusion. Control animals were compared to those exposed to pre-emptive high cervical cord stimulation (SCS; the dorsal aspect of the C1-C2 spinal cord was stimulated electrically at 50 Hz; 0.2 ms; 90% of motor threshold, starting 15 min prior to and continuing throughout CAO). Four groups of animals were so tested: 1) neuroaxis intact; 2) prior cervical vagotomy; 3) prior transection of the dorsal spinal columns at C6; and 4) following pharmacological treatment [muscarinic (atropine) or adrenergic (atenolol, prazosin or yohimbine) receptor blockade]. Infarct size (IS) was measured by tetrazolium, expressed as percentage of risk zone. C1-C2 SCS reduced acute ischemia induced IS by 43%, without changing the incidence of sudden cardiac death (SCD). While SCS-induced reduction in IS was unaffected by vagotomy, it was no longer evident following transection of C6 dorsal columns or atropinization. Beta-adrenoceptor blockade eliminated ischemia induced SCD, while alpha-receptor blockade doubled its incidence. During SCS, myocardial ischemia induced SCD was eliminated following vagotomy while remaining unaffected by atropinization. These data indicate that, in contrast to thoracic spinal neurons, i) cranial cervical spinal neurons affect both adrenergic and cholinergic motor outflows to the heart such that ii) their activation modifies ventricular infarct size and lethal arrhythmogenesis.

Silodosin for the treatment of benign prostatic hyperplasia: pharmacology and cardiovascular tolerability.

Relief of benign prostatic hyperplasia (BPH)-related lower urinary tract symptoms by α-blockers (α1-adrenoceptor antagonists) is mediated primarily through the blockade of α(1A)-receptors, leading to relaxation of smooth muscle in the prostate and bladder neck. Early α-blockers that were nonselective for adrenoceptor subtypes have been associated with blood pressure-related adverse effects, such as orthostatic hypotension, that may be attributed at least in part to the blockade of α(1B)-adrenoceptors in arterial vessels. Silodosin, a novel α-blocker with exceptionally high selectivity for α(1A-) versus α(1B)-adrenoceptors, was recently approved in the United States for the treatment of urinary symptoms related to BPH. The unique receptor selectivity profile likely accounts for some of the desirable clinical features of the drug. Silodosin possesses an excellent cardiac- and blood pressure-related safety profile, and data have demonstrated that it does not promote QT-interval prolongation. Therapeutic doses of silodosin are safe for men with mild-to-moderate liver dysfunction; dosage adjustment is recommended in those with moderate renal impairment. The drug should not be taken with potent cytochrome P450 3A4 inhibitors. Silodosin may be especially beneficial in patients who need to maximize cardiovascular tolerability.

Naftopidil for the treatment of lower urinary tract symptoms compatible with benign prostatic hyperplasia.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a common condition in aging men causing lower urinary tract symptoms (LUTS). Treatment aims are to relieve symptoms and prevent disease progression. Of the different alpha-1 adrenergic receptors (ARs) in the prostate, alpha-1a receptors are known to be central to prostatic smooth-muscle contraction. Recent studies have shown that patients with BPH may also have a predominance of alpha-1d receptors. OBJECTIVES: To evaluate the efficacy and adverse effects of naftopidil, a selective alpha-1d oral alpha-blocking agent for the treatment of LUTS associated with BPH. SEARCH STRATEGY: Systematic review of trials published January 1950 to January 2009. Sources included MEDLINE and bibliographies of retrieved articles and review articles. SELECTION CRITERIA: Eligible trials included: men diagnosed with symptomatic BPH; compared Naftopidil to placebo, control, or combination therapy; evaluated clinically relevant outcomes between randomized groups; had at least 4-weeks follow up; and were published in English language. DATA COLLECTION AND ANALYSIS: Participant demographics and comorbidities, enrollment criteria, outcomes, adverse events, numbers and reasons for dropouts were extracted onto standardized extraction forms by one reviewer. The mean change and per cent improvement from baseline in AUA (American Urological Association Symptom Score) and IPSS (International Prostate Symptom Score) scores and other efficacy outcomes for treatment and control groups were calculated. If feasible, the efficacy outcomes and adverse events data were pooled. MAIN RESULTS: Eight trials were eligible (N = 744 participants). All trials were conducted in Japan. Study duration ranged from 4 to 17 weeks. The mean age of participants was 68 years; pretreatment mean IPSS = 17.8 and mean peak urine flow (Qmax) = 9.5 mL/s (milliliters/second). No trials compared naftopidil to placebo. In 5 trials (N = 419), naftopidil in doses of 25 to 75 mg/d (milligrams/day) showed a mean IPSS improvement similar to low-dose tamsulosin (0.2 mg/d) (8.4 versus 8.9 points). Compared to a phytotherapy preparation (eviprostat), naftopidil significantly improved total IPSS (-5.9 versus 0.4; P < 0.0002). In one trial, the addition of anticholinergic drugs (oxybutynin or propiverine hydrochloride) to naftopidil did not offer any significant improvement for IPSS or Qmax in comparison to treatment with naftopidil alone. Although IPSS did not significantly differ between high- (75 mg/d) and low-dose (25mg/d) naftopidil, high dose significantly improved Qmax compared to low dose (1.2 mL/s versus 0.2 mL/s). Adverse events reported were few, mild and similar to those seen with 0.2 mg/d tamsulosin. AUTHORS' CONCLUSIONS: There are no data from placebo controlled trials regarding the efficacy of naftopidil in men with symptomatic BPH. Limited information suggests that treatment with naftopidil provides short-term improvement in urinary symptom-scale scores (total IPSS/AUA), QoL (quality of life) score, and urinary symptoms from baseline comparable to low-dose tamsulosin. Adverse effects due to naftopidil were few and usually mild.

[Pharmacological treatment of benign prostatic hyperplasia]. / Medikamentöse Therapie der benignen Prostatahyperplasie.

The majority of men with benign prostatic hyperplasia (BPH) seek medical help because of lower urinary tract symptoms (LUTS). Pharmacological treatment of BPH is indicated if the patient has no absolute indications for prostate surgery or benign prostatic obstruction (BPO), but LUTS with a decrease of quality of life. Plant extracts can be prescribed in men with mild to moderate symptoms. alpha-Blockers can quickly and effectively decrease LUTS and symptomatic disease progression. If patients have predominantly bladder filling symptoms and a small prostate, muscarinic receptor antagonists are a viable treatment option. The combination of an alpha-blocker plus a muscarinic receptor antagonist is more effective than single drugs used alone. Especially in men with larger prostates, 5alpha-reductase inhibitors can decrease LUTS and the probability of acute urinary retention as well as need for prostate surgery. The combination of alpha-blocker plus 5alpha-reductase inhibitor can reduce LUTS and disease progression more effectively than single drugs.

Evaluación económica del tratamiento médico de la hiperplasia benigna de próstata (HBP) en España en atención especializada. Aplicación al coste-efectividad de dos fármacos habitualmente utilizados en su tratamiento / Economic evaluation of medical treatment of benign prostatic hyperplasia (BPH) in the specialised care setting in Spain. Application to the cost-effectiveness of two drugs frequently used in its treatment

Objetivos: Llevar a cabo un estudio fármaco económico para conocer el coste medio del diagnóstico y seguimiento de la HBP en España en el ámbito de la atención especializada desde la perspectiva del sistema público de salud, considerando dos fármacos frecuentemente utilizados en el entorno sanitario español, un alfabloqueante (tamsulosina) y el extracto lipido esterólico de Serenoa repens (Permixón(R)).Material y métodos: Se determinaron los costes sanitarios directos del diagnóstico y tratamiento de la HBP para cada presentación clínica según el valor del International Prostate Symptom Score (IPSS): leve, moderada y grave. Los datos sobre el consumo y los costes unitarios de los recursos sanitarios se recogieron mediante una encuesta semi-estructurada a expertos clínicos. La eficacia clínica del tratamiento médico fue obtenida del estudio clínico PERMAL, en el que se observó equivalencia terapéutica entre ambos fármacos. Resultados: El coste medio anual de pruebas diagnósticas y visitas médicas de la HBP sintomática según fuese leve, moderada o grave fueron, respectivamente, 124 €, 207€ y 286€ para pacientes tratados en atención especializada. El coste medio anual del tratamiento médico, incluyendo la atención de los efectos adversos fue de 211€ para Permixón(R) y 346 € paratamsulosina. Discusión: El coste de la atención médica de la HBP es proporcional a la intensidad de la sintomatología. El tratamiento farmacológico constituye una parte significativa del coste de la enfermedad. En base al modelo utilizado, el tratamiento con Permixón(R) es sensiblemente más coste-efectivo que el tratamiento con tamsulosina, representando un ahorro medio de 135€ por paciente y año (AU)

Objectives: To develop a pharmaco economic study in order to know the average cost of BPH diagnosis and follow-up in Spain in the Urology Department setting from the perspective of the public health system, considering two frequently used drugs in the Spanish Healthcare environment, an alpha-blocker (tamsulosin) and the lipido-sterolic extract of Serenoa repens (Permixon(R)).Material and methods: Direct healthcare costs of BPH diagnosis and treatment were determined for each clinical stage according to the International Prostate Symptom Score (IPSS): mild, moderate and severe. Data on the usage and unit costs of healthcare resources were obtained from a semi-structured interview with clinical experts. The clinical efficacy of the medical treatments was obtained from the PERMAL clinical study, where therapeutic equivalence between the two studied drugs was observed. Results: For patients treated in the Urology Department setting, the average annual cost of diagnostic tests and medical visits related to mild, moderate or severe BPH symptoms were, respectively, € 124, € 207, and € 286. The average annual cost of the drugs, including adverse effects treatment, was € 211 for Permixon(R) and € 346 for tamsulosin. Discussion: Costs of medical care of BPH increases with symptom intensity. Pharmacological treatment makes up a significant part of the disease’s cost. According to the model used, treatment with Permixon(R) is considerably more cost-effective than with tamsulosin, offering average yearly savings of € 135 per patient (AU)

[Botulinum toxin in the treatment of benign prostatic hyperplasia : an overview]. / Botulinumtoxin in der Therapie der benignen Prostatahyperplasie : Ein Uberblick.

The aim of this article is to provide a state-of-the-art review about the treatment of benign prostatic hyperplasia with botulinum toxin injections into the prostate. We searched PubMed for original articles until July 2007. Abstracts published at international congresses were also considered if they contributed substantial new information. Injections were performed mostly via the transperineal route under local anesthesia.From this review it appears that a majority of patients with benign prostatic hyperplasia experiences an improvement of both subjective parameters (IPSS, AUA symptom score) and objective parameters such as peak flow rate, postvoid residual volume, and prostate volume. An effect could be shown for different patient groups including different prostate sizes and different symptom characteristics. A high success rate and sustained duration of the effect of at least 12 months could be achieved. Side effects were marginal, and no systemic side effects were reported.Placebo-controlled studies with sufficient patient numbers and long-term follow-up are needed to determine the future value of this procedure in the treatment of patients with benign prostatic hyperplasia.

[Contemporary medical management of the benign prostatic syndrome]. / Aktuelle Aspekte der medikamentösen Therapie bei benignem Prostatasyndrom (BPS).

Two groups of drugs, alpha blockers and 5-alpha-reductase inhibitors (5ARI), are currently widely used for the medical treatment of benign prostatic syndrome (BPS). Alpha blockers are characterized by a rapid onset of efficacy. If given at an adequate dose, all alpha blockers have a similar efficacy, yet quantitative differences regarding side effects exist. The onset of clinical efficacy of 5ARIs is delayed and dependent on prostate volume. Symptom improvement is generally less pronounced than with alpha blockers, yet this difference declines with time. 5ARI, in contrast to alpha blockers, reduce prostate volume and the risk of long-term BPS complications such as prostate surgery or acute urinary retention. The combination therapy of alpha blockers and 5ARI is superior to either monotherapy; however, this superiority becomes evident only after prolonged (>1 year) therapy. Because of additive side effects, this combination should be reserved for BPS patients with a high risk of progression. Regarding plant extracts, no definitive recommendation can be given because of a limited number of high-quality clinical trials. The use of antimuscarinics in men with BPS with a dominance of storage symptoms and without significant obstruction is promising, although further trials, particularly with a longer study duration, are required.

Alpha-2 adrenergic antagonism enhances risk of ventricular tachycardia during acute ischemia.

OBJECTIVE: In this study we tested the hypothesis that alpha-2 adrenergic antagonism could facilitate induction of previously non-inducible ventricular tachycardia (VT) during acute ischemia. Previous reports suggest that VT during ischemia may be modulated by (alpha-2 adrenergic agonists. DESIGN: The left anterior descending artery was occluded after instrumentation of the ischemic risk zone with 21 multipolar plunge needles, each recording 6 bipolar electrograms. Three dimensional mapping characterized the mechanism of VT induced with extrastimuli. RESULTS: Of 16 non-inducible dogs included, eight which were given the alpha-2 adrenergic antagonist yohimbine all had inducible VT, while all eight in the control group remained non-inducible (p < 0.05). Six of the VTs were of focal Purkinje origin. The cycle length of the VTwas 119 +/- 4 ms. Mean arterial pressure (81+/- 8 to 82 +/- 8 mmHg, p = ns), ventricular effective refractory period (146 +/- 6 to 144 +/- 5 ms, p = ns) and ischemic zone size (55 +/-6% vs. 61 +/- 4%, p = 0.45) were not altered by yohimbine indicating minimal central or pre-junctional effects of the drug. CONCLUSIONS: Yohimbine facilitates induction of VT, especially those with focal Purkinje fiber origin, suggestive of an effect mediated through antagonism of post-junctional alpha-2 adrenoceptors on Purkinje fibers.

[Expediency of switching from combined therapy with prostamol Uno and alpha-1-adrenoblockers to monotherapy with prostamol Uno in patients with prostatic adenoma].

A 9-month randomized open comparative trial was performed of efficacy and safety of combined treatment with prostamol Uno and tamsulosin followed by monotherapy with prostamol Uno. A total of 58 patients with prostatic adenoma (PA) treated with prostamol Uno in combination with tamsulosin were divided into two groups: 28 patients continued the above combined therapy, 30 patients were switched to monotherapy with prostamol Uno. All the patients were examined in the course of 4 visits according to standard protocol requesting information on the disease history, complaints, digital rectal examination, IPSS questionnaire, QOL, uroflowmetry with test for residual urine, transrectal ultrasonography of the prostate, blood test for PSA. The results of the trial show reduction of IPSS and QOL indices in 87% patients. QOL improved both in group 1 after 3 months of combined treatment and in group 2 who continued on monotherapy with prostamol Uno to the end of month 9 (p < 0.05). Q(max) change was statistically the same in both groups. To the end of treatment month 9 the size of the prostate diminished by 6.7 cm3, on the average, in both groups. PSA levels changed insignificantly (p > 0.05). Prostamol Uno was especially safe for hypotensive patients and those on antihypertensive therapy. After discontinuation of tamsulosin 100% patients of group 2 stopped exhibiting symptoms of retrograde ejaculation. None cases of a hypotonic reaction to the drug were registered. Mean cost of a course of therapy in group 1 to that of group 2 was 1:3.16. Thus, pharmacotherapy with prostamol Uno in moderate symptoms of PA is comparable in efficacy with combination prostamol Uno + tamsulosin, is safe and cost-effective.

Incontinence related to management of benign prostatic hypertrophy.

BACKGROUND: The prevalence of incontinence ranges from 11% to 34% among community-dwelling men aged > or =65 years. OBJECTIVE: The objective of this analysis was to determine the nature of incontinence diagnosed in men with benign prostatic hypertrophy (BPH), focusing on its incidence, prevalence, diagnostic workup, and management. METHODS: A cohort of patients with BPH was identified in the Integrated Healthcare Information Services National Managed Care Benchmark Database (1997-2003). Age and duration in the database after the first diagnosis of BPH were used as matching strata. Therapeutic subgroups consisted of watchful waiting, alpha-blockers, 5-alpha-reductase inhibitors (5ARIs), and BPH-related surgery. RESULTS: A total of 411,658 males with BPH were identified from 12,298,027 males (3.3%). Of the BPH cohort, 2.7% (n = 11,172) were identified as having incontinence; of these, 57.8% of patients were > or =65 years of age. Alter applying inclusion/exclusion criteria, the final matched case-control sample included 6346 men as case subjects and 229,154 men as control subjects. The overall incidence of incontinence in this BPH sample was 1835/100,000/year, and the prevalence was 2713/100,000 men. In 48.5% of the incontinent men, the type of incontinence was not specified. Diagnostic testing was performed in 2.9% of men with incontinence. Conditional logistic regression analyses found that BPH-related surgery and alpha-blocker use increased the adjusted odds ratio for the risk of incontinence 3.1-fold, and 1.1- to 1.7-fold, respectively. The odds ratio of the risk of incontinence was not significantly increased with long-term 5ARI use. CONCLUSIONS: Use of alpha-blockers, 5ARIs for the short term (<1 year), and BPH-related surgery were independently, significantly associated with BPH-related incontinence; 5ARI use for >1 year and watchful waiting were not. BPH-related incontinence may be related to progression of BPH or as a postsurgical complication. Patients with BPH should be asked specifically about incontinence, especially after BPH-related surgery, and undergo a full diagnostic workup for the diagnosis of urinary incontinence.