Patient characteristics and treatment patterns for patients with benign prostatic hyperplasia, erectile dysfunction or co-occurring benign prostatic hyperplasia and erectile dysfunction in general practices in the UK: a retrospective observational study.

AIMS: The aim of this study was to assess patient characteristics, medication treatment patterns and healthcare resource utilization among men with existing erectile dysfunction (ED) or benign prostatic hyperplasia (BPH), who are newly diagnosed with the second condition (BPH or ED) compared with those with only one condition. METHODS: This retrospective cohort study utilized the Clinical Practice Research Datalink. Males, aged 40 years or older, newly diagnosed with ED or symptomatic BPH between 1 June 2010 and 31 May 2011, were selected. Patient demographics, existing comorbidities and baseline medication use were analysed. Treatments initiated for the incident condition and treatment patterns were reported at 6, 12, 18 and 24-months postdiagnosis. Referrals to urologists and visits to general practitioners were reported around diagnosis and during follow-up. RESULTS: This study included 11,501 incident patients with BPH, of which 23% had a prior ED diagnosis and 9,734 incident patients with ED, of which 17% had a prior BPH diagnosis. The average age at diagnosis of BPH was similar across both cohorts. Among incident patients with ED, those with prior diagnosis of BPH were diagnosed at an older average age (65 ± 9.2 years) compared to those without BPH (57 ± 9.1 years). The majority of patients in both incident BPH cohorts (62.9-65.5%) were prescribed alpha-blockers as initial treatment. The majority of patients in both incident ED cohorts (49.6-51.6%) were prescribed sildenafil as initial treatment followed by tadalafil (24.3-26.0%). At 12 months, 50% of incident patients with BPH and 80% of patients with ED had discontinued the therapy initiated. CONCLUSION: This study found that in the UK, patients with co-occurring BPH and ED when newly diagnosed with the second condition initiated the same treatments as those without prior ED or BPH. During the first year, treatment patterns including discontinuation were comparable in the groups with one of the conditions and co-occurring BPH and ED.

Development of UK recommendations on treatment for post-surgical erectile dysfunction.

AIM: To develop a management strategy (rehabilitation programme) for postsurgical erectile dysfunction (ED) among men experiencing ED associated with treatment of prostate, bladder or rectal cancer that is suitable for use in a UK NHS healthcare context. METHODS: PubMed literature searches of ED management together with a survey of 13 experts in the management of ED from across the UK were conducted. RESULTS: Data from 37 articles and completed questionnaires were collated. The results discussed in this study demonstrate improved objective and subjective clinical outcomes for physical parameters, sexual satisfaction, and rates of both spontaneous erections and those associated with ED treatment strategies. CONCLUSION: Based on the literature and survey analysis, recommendations are proposed for the standardisation of management strategies employed for postsurgical ED.

Prevalence and detection rate of underlying disease in men with erectile dysfunction receiving phosphodiesterase type 5 inhibitors in the United Kingdom: a retrospective database study.

AIM: To determine the rate of newly detected underlying disease in men receiving their first (index) phosphodiesterase type 5 inhibitor (PDE5i) prescription. METHODS: This non-interventional, retrospective study used anonymised patient records from UK general practices identified from the THIN database. Records of men aged ≥ 18 years, who received an index PDE5i prescription between January 1999 and June 2008 and with a continuous medical history (≥ 60 months) before the index prescription were included. Primary end-points were the prevalence of underlying disease prior to the index prescription and to establish the detection rate, defined as cumulative incidence of such a diagnosis in the 3 months following the index prescription. Assessments included comparison with age-matched controls, comparison with identical time periods immediately before and 1 year after, index prescription, and changes over time during the study period. Descriptive statistics, analysis of proportions and multivariate logistic regression analysis were used. RESULTS: Among the 24,708 patients receiving a PDE5i, the prevalence of any underlying diagnosis before the index prescription was 70.23%; prevalence of vasculogenic disease was highest (48.20%). The detection rate of any underlying disease was 11.53%, and again highest for vasculogenic disease (4.07%). Compared with an age-matched control population, the additional detection rate of an unknown underlying disease at PDE5i prescription was 45 for hypertension, 61 for hypercholesterolaemia, 38 for diabetes and 5 for hypogonadism per 10,000 men. CONCLUSION: Only a minority of men with erectile dysfunction have a previously undiagnosed important underlying disease that is uncovered at the time of an initial PDE5i prescription by a GP.

Pelvic organ prolapse and overactive bladder.

AIMS: In this review we try to shed light on the following questions: *How frequently are symptoms of overactive bladder (OAB) and is detrusor overactivity (DO) present in patients with pelvic organ prolapse (POP) and is there a difference from women without POP? *Does the presence of OAB symptoms depend on the prolapsed compartment and/or stage of the prolapse? *What is the possible pathophysiology of OAB in POP? *Do OAB symptoms and DO change after conservative or surgical treatment of POP? METHODS: We searched on Medline and Embase for relevant studies. We only included studies in which actual data about OAB symptoms were available. All data for prolapse surgery were without the results of concomitant stress urinary incontinence (SUI) surgery. RESULTS: Community- and hospital-based studies showed that the prevalence of OAB symptoms was greater in patients with POP than without POP. No evidence was found for a relationship between the compartment or stage of the prolapse and the presence of OAB symptoms. All treatments for POP (surgery, pessaries) resulted in an improvement in OAB symptoms. It is unclear what predicts whether OAB symptoms disappear or not. When there is concomitant DO and POP, following POP surgery DO disappear in a proportion of the patients. Bladder outlet obstruction is likely to be the most important mechanism by which POP induces OAB symptoms and DO signs. However, several other mechanisms might also play a role. CONCLUSIONS: There are strong indications that there is a causal relationship between OAB and POP.

Screening in general practice.

Screening for prostate cancer in a general practice setting seems to be technically feasible and generally acceptable. In our study, 14 cancers were diagnosed among the 568 men screened, giving an overall detection rate of 2%; five of these were either locally advanced or associated with metastatic disease. Although these results may reflect our somewhat conservative biopsy rate, there is a considerable false positive rate in the PSA range of 4-10 ng/ml, particularly among men with clinical evidence of benign prostatic hyperplasia. A large scale prospective controlled study will be necessary to establish the true benefit of screening.

Screening for carcinoma of the prostate: a GP based study.

OBJECTIVE: To examine the feasibility and acceptability of screening for cancer of the prostate by digital rectal examination (DRE), prostate specific antigen (PSA) determination and subsequent transrectal ultrasound (TRUS) in selected patients in a single general practice in Hertfordshire. SUBJECTS AND METHODS: A total of 568 of 856 men aged 55 to 70 accepted an invitation for a health check which included screening for prostate cancer. Of these, 80 individuals with either a raised PSA level or an abnormal DRE underwent TRUS. In 29 individuals biopsies were taken, 11 of which confirmed the presence of adenocarcinoma of the prostate giving an overall detected prevalence of 2%. Of the 11 tumours identified by screening, two were T1M0, four were T2M0, two were T3M0 and three were T3M1. RESULTS: To assess the acceptability of the screening exercise a postal questionnaire was sent to all 568 participants: 83% replied and 69% reported no concern. Of the 67 individuals who had undergone TRUS, 69% reported discomfort. A total of 448 (95%) of respondents declared that they would be prepared to undergo the screening exercise again. CONCLUSION: Screening for prostate cancer would seem to be technically feasible and generally acceptable. However, there is a considerable false positive rate in the PSA range 4 ng/ml to 10 ng/ml, particularly among men with clinical evidence of benign prostatic hyperplasia. To establish the true benefit of screening a large-scale prospective controlled study will be necessary.

A multicentre study of the safety and efficacy of amlodipine in mild to moderate hypertension.

An open, non-comparative study of 10 weeks' duration was conducted in general practice to assess the safety of amlodipine in patients with mild to moderate hypertension. Of the 5352 patients entering the study, 5135 received amlodipine; 4621 patients (90%) with a mean age of 58.2 years completed the study. Normalisation of blood pressure was achieved in over 80% of patients with a mean reduction of 21/15 mmHg. The mean final dose of amlodipine was 6.8 mg/day. Adverse experiences possibly related to amlodipine were reported by 19.3% of patients, and overall adverse events led to withdrawal in 6.7% of patients. The most common reported side-effect was oedema. The frequency of headache was almost identical in older and younger patients and oedema, flushing and dizziness were seen only slightly more often in elderly patients. Ninety per cent of patients were considered by their GP to have shown excellent or good toleration of therapy. Over 85% of patients elected to continue on amlodipine therapy after completion of the study.

Effect of altering small bowel transit time on sustained release theophylline absorption.

The relationship between variations in small bowel transit time (SBTT) and the absorption of theophylline from a sustained-release product was evaluated in a three-way, randomized, crossover study in 12 healthy male nonsmokers. Subjects received sustained-release theophylline (600 mg) with loperamide (8 mg every 6 hour x 8 doses). metoclopramide (15 mg every 6 hour x 8 doses) or placebo (every 6 hour x 8 doses). Theophylline solution (400 mg) was used as a reference standard. Serum samples were collected periodically for 72 hours for theophylline concentration determinations. SBTT was measured by the lactulose hydrogen breath test. Compared with placebo (98 +/- 53 min), SBTT was increased with loperamide (211 +/- 87 min; P less than 0.001) and decreased with metoclopramide (55 +/- 18 min; P less than 0.001). Loperamide decreased the rate, but not the extent of theophylline absorption from this product. This was evident from the reduced Cmax, the prolonged Tmax, and the decreased fraction of the dose absorbed at 24 hours, while the area under the curves remained the same. In contrast, metoclopramide had no effect either on rate or extent of absorption. The data suggest that the effect of loperamide on these absorption parameters was due to an increase in the dissolution time of this sustained-release product.

Effect of metoclopramide, bethanechol, and loperamide on gastric residence time, gastric emptying, and mouth-to-cecum transit time.

The effects of metoclopramide, bethanechol, and loperamide on the gastric residence time (GRT), gastric emptying (GE), and mouth-to-cecum transit time (MCTT) of a solution were investigated in three separate studies of five healthy male volunteers each. Metoclopramide in doses of 5, 10, and 15 mg prolonged GRT by 33, 88, and 162%, respectively, almost reaching statistical significance (p 0.058). A relationship was observed between GRT prolongation, and metoclopramide area under the plasma-time curve (p 0.01) and metoclopramide observed time to maximum concentration (p 0.01). Metoclopramide had an inconsistent effect on MCTT. Bethanechol 50 mg prolonged GRT by 64% (p 0.031) and had no effect on MCTT. Loperamide at doses of 2 and 8 mg prolonged GRT by 18 and 115% (p 0.043) and MCTT by 30 and 130% (p 0.0001), respectively. None of these motility-altering agents affected GE.

Pharmacology and therapeutic use of low-dose dopamine.

The renal pharmacologic effects of intravenous dopamine in doses of 0.5-3.0 micrograms/kg/min include increases in renal blood flow, glomerular filtration rate, solute excretion, and urine flow. Clinical studies revealed that low-dose dopamine can reverse oliguria, but these studies were poorly controlled, were confounded by the use of other diuretics, had small patient populations, and often did not evaluate mortality or long-term renal function. When used in low doses, side effects are rarely seen. Because of dopamine's effect on hepatic and renal function, changes in drug clearance may occur. Low-dose dopamine may be considered in the early course of oliguric patients; however, specific advantages over other diuretic therapy have not been established.

Effect of low-dose dopamine on the pharmacokinetics of tobramycin in dogs.

Low-dose dopamine or a placebo was given to six healthy mongrel dogs, each receiving tobramycin at 2.0 mg/kg on consecutive days in a randomized crossover fashion. Dopamine increased the total and renal clearances and elimination rate constant of tobramycin by 12.5, 20, and 25.9%, respectively, suggesting that low-dose dopamine increases the clearance of tobramycin in dogs primarily through renal mechanisms.