Tolterodine extended release is well tolerated in older subjects.

OBJECTIVES: To investigate the tolerability of tolterodine extended release (ER) in older subjects with overactive bladder (OAB). METHODS: This was a retrospective analysis of pooled data from five large, randomised, double-blind, placebo-controlled trials. Subjects with OAB symptoms, including urinary frequency and urgency (and nocturia in two studies) with or without urgency urinary incontinence, received qd treatment with tolterodine ER (4 mg) or placebo for 8-12 weeks. Data were stratified post hoc by age group: < 65 (n = 2531), 65-74 (n = 1059) and > or = 75 years (n = 573). Tolerability was assessed by evaluating the occurrence of adverse events (AEs). AE occurrences from each study were mapped to the MedDRA coding dictionary of preferred terms. RESULTS: Discontinuation rates were slightly higher among subjects > or = 75 years of age vs. those < 65 years of age; however, this was observed in subjects treated with placebo as well as tolterodine ER. Overall, there were no significant differences in the occurrence of dry mouth, headache, constipation, nausea, urinary tract infection, blurred vision, dry eye, dizziness and micturition disorder in older (65-74 or > or = 75 years) vs. younger (< 65 years) subjects treated with tolterodine ER relative to placebo (treatment x age; all p > 0.1). Dry mouth was the only AE consistently associated with tolterodine ER treatment (< 65 years, 17%; 65-74 years, 16%; > or = 75 years, 15%). The occurrence of all other AEs was < or = 5% in most age and treatment cohorts. Most AEs were mild or moderate in all age and treatment cohorts. CONCLUSION: The nature and frequency of AEs associated with tolterodine ER treatment were similar across age groups in subjects with OAB, suggesting that tolterodine ER was not associated with an increased risk of AEs in older vs. younger subjects and, thus, is a suitable first-line pharmacotherapy treatment for OAB in this population.

A population-based survey of sexual activity, sexual problems and associated help-seeking behavior patterns in mature adults in the United States of America.

To study sexual activity, the prevalence of sexual dysfunction and related help-seeking behaviors among mature adults in the United States of America, a telephone survey was conducted in 2001-2002. A total of 1491 individuals (742 men/749 women) aged 40-80 years completed the survey. Overall, 79.4% of men and 69.3% of women had engaged in sexual intercourse during the 12 months preceding the interview. Early ejaculation (26.2%) and erectile difficulties (22.5%) were the most common male sexual problems. A lack of sexual interest (33.2%) and lubrication difficulties (21.5%) were the most common female sexual problems. Less than 25% of men and women with a sexual problem had sought help for their sexual problem(s) from a health professional. Many men and women in the United States report continued sexual interest and activity into middle age and beyond. Although a number of sexual problems are highly prevalent, few people seek medical help.

Relationships between improvements in symptoms and patient assessments of bladder condition, symptom bother and health-related quality of life in patients with overactive bladder treated with tolterodine.

AIMS: Relationships were evaluated between treatment-related improvements in overactive bladder (OAB) symptoms as recorded in bladder diaries and patient-reported symptom bother, bladder-related problems and health-related quality of life (HRQL). METHODS: A post hoc analysis was performed on data from patients with OAB (n = 863) enrolled in a 12-week open-label trial of tolterodine extended release (ER) in a primary care setting. At baseline and week 12, patients recorded every micturition, urgency episode and urgency urinary incontinence episode in 3-day bladder diaries. Patients also completed the Overactive Bladder Questionnaire (OAB-q) and Patient Perception of Bladder Condition (PPBC). Relationships between week 12 changes in bladder diary variables and OAB-q and PPBC scores were evaluated using Spearman correlations. RESULTS: By week 12, tolterodine ER-related improvements in all bladder diary variables were significantly correlated with improvements on the PPBC (r = 0.26-0.36; p < 0.001), OAB-q Symptom Bother scale (r = 0.30-0.51; p < 0.001), and all OAB-q HRQL domains (r = -0.24 to -0.42; p < 0.001), although the correlations were generally small to moderate in size. Improvements on the PPBC were also significantly correlated with improvements on the OAB-q Symptom Bother scale (r = 0.63; p < 0.001) and all HRQL domains (r = -0.40 to -0.59; p < 0.001). CONCLUSIONS: Tolterodine ER-related improvements in OAB symptoms (assessed by diary variables) and patients' perceptions of the changes in symptom bother, bladder-related problems and HRQL (assessed by PPBC and OAB-q) were significantly correlated. The OAB-q and the PPBC provide a relevant and important patient perspective for OAB treatment evaluation.

Cardiovascular outcomes among sildenafil users: results of the International Men's Health Study.

AIM: To assess the incidence of serious cardiovascular disease (CVD) events [i.e. myocardial infarction (MI) and stroke] and all-cause mortality in men with erectile dysfunction (ED) who received prescriptions for sildenafil. METHODS: The International Men's Health Study (IMHS) was a prospective, observational cohort study of patients with ED and a new or existing prescription for sildenafil. Baseline and follow-up questionnaires provided information on demographics, CVD risk factors and ED. Postevent questionnaires were mailed to patients following possible nonfatal CVD events to collect information related to exposure to sildenafil/ED treatments before the event. RESULTS: Thirty-five CVD events were reported in 30 patients in the analysis set (n = 3813). The incidence of all-cause mortality, MI and stroke was 0.4, 0.6 and 0.1 per 100 patient-years of observation respectively. Among the six men who reported using sildenafil in the month before a nonfatal CVD event, two reported use in the 24 h before the event. CONCLUSION: The results of the IMHS support previous reports that ED and CVD are often comorbid and share risk factors.

Prevalence of storage and voiding symptoms among men aged 40 years and older in a US population-based study: results from the Male Attitudes Regarding Sexual Health study.

AIMS: Lower urinary tract symptoms (LUTS) are categorised as storage (urgency, frequency, nocturia and incontinence), voiding (sensation of incomplete emptying, hesitancy, weak stream and straining) or mixed symptoms. METHODS: In this US population-based study, we investigated the prevalence of male LUTS and the relative frequency of the LUTS subtypes, and we evaluated associations between LUTS and age, race/ethnicity and erectile dysfunction (ED). The Male Attitudes Regarding Sexual Health study included a nationally representative sample of non-Hispanic black, non-Hispanic white and Hispanic men aged>or=40 years. Participants completed a questionnaire including items on ED and the International Prostate Symptom Score (IPSS). The prevalence and subtypes of LUTS were investigated post hoc by age, race/ethnicity and the presence of ED. RESULTS: The overall prevalence rates of storage (13%) and mixed (9%) symptoms were higher than that of voiding symptoms (6%). The prevalence of storage symptoms was similar across age groups, whereas voiding and mixed symptoms increased with age. Among men with IPSS>or=8, the rates of storage (29%) and mixed (38%) symptoms were also higher than voiding symptoms (23%). Distributions of the LUTS subtypes were comparable among black, white and Hispanic respondents with IPSS>or=8. The overall prevalence rate of ED (40%) increased with age among those with IPSS>or=8. Isolated storage symptoms were more than twice as common as isolated voiding symptoms among US men>or=40 years of age. CONCLUSION: Careful attention to individual symptoms may help distinguish storage LUTS from voiding LUTS, a distinction that has important implications for treatment.

A retrospective study of the relationship between biomarkers of atherosclerosis and erectile dysfunction in 988 men.

Erectile dysfunction (ED) is associated with clinical atherosclerosis and several atherosclerotic risk factors including smoking, hypertension, dyslipidemia, diabetes mellitus, obesity and sedentary lifestyle. Clinical atherosclerosis is also associated with these same risk factors and with biomarkers of inflammation, thrombosis, endothelial cell activation. We evaluated the cross-sectional association between the degree of ED and levels of atherosclerotic biomarkers. A subcohort of 988 US male health professionals between the ages 46 and 81 years as part of an ongoing epidemiologic study had atherosclerotic biomarkers measured from blood collected in 1994-1995. These same men had in 2000, been retrospectively asked about erectile function in 1995 and in 2000. Biennial questionnaires since 1986 assessed medical conditions, medications, smoking, physical activity, body mass index, alcohol intake. The retrospective assessment of erectile function in 2000 for 1995 in these 988 men ranged from very good - 28.2%, good - 25.1%, fair - 19.2%, poor - 13.6%, to very poor - 13.9%. Men with poor to very poor erectile function compared to men with good and very good erectile function had 2.9 the odds of having elevated Factor VII levels (P=0.03), 1.9 times the odds of having elevated vascular cell adhesion molecule (P=0.13) and 2.0 times the odds of having elevated intracellular adhesion molecule (P=0.06) and 2.1 times the odds of having elevated total cholesterol/high-density lipoprotein ratio (P=0.02) comparing the top to bottom quintiles for each atherosclerotic biomarker after multivariate adjustment. Lipoprotein(a), homocysteine, interleukin-6 and tumor necrosis factor receptor, C-reactive protein and fibrinogen were not associated with the degree of erectile function after adjustment. We conclude that selected biomarkers for endothelial function, thrombosis and dyslipidemia but not inflammation are associated with the degree of ED in this cross-sectional analysis. Future studies evaluating the prospective association of ED, endothelial function and cardiovascular disease appear warranted.

Symptom-specific efficacy of tolterodine extended release in patients with overactive bladder: the IMPACT trial.

We evaluated the efficacy of tolterodine extended release (ER) for patients' most bothersome overactive bladder (OAB) symptom in a primary care setting. Patients with OAB symptoms for >or=3 months received tolterodine ER (4 mg q.d.) for 12 weeks. Among incontinent patients (n = 772), the most bothersome OAB symptoms were daytime frequency (28%), urgency urinary incontinence (UUI; 27%), nocturnal frequency (26%) and urgency (19%); among continent patients (n = 91), they were daytime frequency (47%), nocturnal frequency (42%) and urgency (10%). Sixty-nine per cent of patients had one or more comorbid conditions. By week 12, there were significant reductions in patients' most bothersome symptom: -80% for UUI, -78% for urgency episodes, -40% for nocturnal frequency and -30% for daytime frequency (p < 0.0001). The most common adverse events were dry mouth (10%) and constipation (4%). In primary care practice, bothersome OAB symptoms can be effectively and safely treated with tolterodine ER, even in patients with comorbid conditions.

Tolterodine extended release improves patient-reported outcomes in overactive bladder: results from the IMPACT trial.

We evaluated the effect of tolterodine extended release (ER) on patient- and clinician-reported outcomes in a primary care setting. Patients had overactive bladder (OAB) symptoms for >or=3 months and were at least moderately bothered by their most bothersome symptom, as indicated on the patient-completed OAB Bother Rating Scale. Patients completed the Overactive Bladder Questionnaire (OAB-q), American Urological Association Symptom Index (AUA-SI), and Patient Perception of Bladder Condition at each visit; investigators completed the Clinical Global Impression-Improvement at week 12. By week 12, there were statistically significant and clinically meaningful decreases on the OAB-q and AUA-SI total and subscale scores (p < 0.0001). Seventy-nine per cent of patients experienced some improvement in their overall bladder condition. Physicians reported that 68% of patients were 'much improved' or 'very much improved'. For symptom-defined conditions, patient-reported outcomes are a valuable means for determining responses to treatment.

A population survey of sexual activity, sexual dysfunction and associated help-seeking behavior in middle-aged and older adults in Germany.

The Global Study of Sexual Attitudes and Behaviors was a survey of 27,500 men and women aged 40 to 80 years in 29 countries. Here we report the sexual activity, the prevalence of sexual problems and related help-seeking behaviour among subjects in Germany. A telephone survey was conducted in 2001 and 2002, using a standardised questionnaire covering demographics, general health, relationships, and sexual behaviours, attitudes and beliefs. A total of 1,500 individuals in Germany (750 men and 750 women) completed the survey. Eighty-six percent of men and 66% of women had engaged in sexual intercourse during the year preceding the interview. The most common male sexual problems were early ejaculation (15%), a lack of sexual interest, erectile dysfunction and non-pleasurable sex (each 8%). The most common female sexual problems were a lack of sexual interest (18%), non-pleasurable sex (14%) and lubrication difficulties (13%). Most sexual problems were less common among men and women in Germany than in other European regions. Increasing age was a significant predictor of a lack of sexual interest and erectile difficulties in men. Only 18% of men and 15% of women had talked to a doctor about their sexual problem(s). In conclusion, many middle-aged and older German adults reported continued sexual interest and activity. Overall, sexual problems were less prevalent in Germany compared with other European regions. Of those who experienced sexual problems, however, few had sought medical help. This was often due to a lack of perception of a problem.

Help-seeking behaviour for sexual problems: the global study of sexual attitudes and behaviors.

The Global Study of Sexual Attitudes and Behaviors (GSSAB) investigated various aspects of sex and relationships among 27,500 men and women aged 40-80 years. Here, we report help-seeking behaviours for sexual problems in this population. A questionnaire was administered using the accepted survey method in each country. Although almost half of all sexually active respondents had experienced at least one sexual problem, less than 19% of them (18.0% of men and 18.8% of women) had attempted to seek medical help for their problem(s). The most frequent action taken by men and women was to talk to their partner (39%). Only 9% of men and women had been asked about their sexual health by a doctor in a routine visit during the past 3 years. Although sexual problems are highly prevalent, few men and women seek medical help for these problems. Overall, men and women show similar help-seeking behaviours.

Sexual problems among women and men aged 40-80 y: prevalence and correlates identified in the Global Study of Sexual Attitudes and Behaviors.

The Global Study of Sexual Attitudes and Behaviors (GSSAB) is an international survey of various aspects of sex and relationships among adults aged 40-80 y. An analysis of GSSAB data was performed to estimate the prevalence and correlates of sexual problems in 13,882 women and 13,618 men from 29 countries. The overall response rate was modest; however, the estimates of prevalence of sexual problems are comparable with published values. Several factors consistently elevated the likelihood of sexual problems. Age was an important correlate of lubrication difficulties among women and of several sexual problems, including a lack of interest in sex, the inability to reach orgasm, and erectile difficulties among men. We conclude that sexual difficulties are relatively common among mature adults throughout the world. Sexual problems tend to be more associated with physical health and aging among men than women.

Clinical trials of sildenafil citrate (Viagra) demonstrate no increase in risk of myocardial infarction and cardiovascular death compared with placebo.

We pooled data regarding myocardial infarction (MI) and cardiovascular death from more than 120 clinical trials of sildenafil citrate (Viagra) conducted from 1993 to 2001. During placebo-controlled trials, the rate of MI or cardiovascular death was 0.91 (95% CI: 0.52-1.48) per 100 person-years (PY) of follow-up among sildenafil-treated patients compared with 0.84 (95% CI: 0.39-1.60) per 100 PY of follow-up among placebo-treated patients. The relative risk of MI or cardiovascular death was 1.08 (95% CI: 0.45-2.77) for sildenafil compared with placebo (p = 0.88). During open-label studies, the rate of MI or cardiovascular death was 0.56 (95% CI: 0.44-0.72) per 100 PY of follow-up. This analysis showed that the rates of MI and cardiovascular death were low and comparable between men treated with sildenafil and those treated with placebo. The use of sildenafil was not associated with an increase in the risk of MI or cardiovascular death.

Prevalence of erectile dysfunction and associated factors among men without concomitant diseases: a population study.

We interviewed a population sample of 2412 men aged 40-70 y in Brazil, Italy, Japan and Malaysia about medical history, lifestyle habits and sexual behavior. Men were classified as having moderate or complete erectile dysfunction (ED) if they reported to be sometimes or never able to achieve and maintain an erection satisfactory for sexual intercourse, respectively. There were 1335 men with no diagnosis of cardiovascular or prostate diseases, diabetes, ulcer or depression, nor taking hormones. The prevalence of ED was 16.1%. ED was associated with age (the risk increased 8% per y), moderate (odds ratio (OR)=2.2) or severe (OR=4.9) lower urinary tract symptoms and smoking (OR=2.3 for >30 cigarettes/day). It was inversely associated with physical activity (OR=0.5) and higher educational levels. Between the ages of 40 and 70 y, almost one in six 'healthy' men is affected by ED. Further research should look at preclinical disease stages and genetic factors.

Prevalence of erectile dysfunction and its correlates among men attending primary care clinics in three countries: Pakistan, Egypt, and Nigeria.

The prevalence and correlates of erectile dysfunction (ED) in developing countries are largely unknown. Our objectives were to determine the prevalence and associated factors of ED in three countries (Pakistan, Egypt, Nigeria) that represent very different cultures. Men 35-70y of age seeking primary medical care answered a structured questionnaire adapted to reflect local cultures. Degree of ED was categorized as 'none,' 'mild,' 'moderate,' or 'complete.' The age-adjusted prevalence rates of ED among men attending primary care clinics was 57.4% in Nigeria, 63.6% in Egypt, and 80.8% in Pakistan. Older age, diabetes, peptic ulcers, prostate disease, depression-related symptoms, and caffeine consumption were independently associated with increased prevalence of ED, whereas being moderately active to very active at work (hard physical labor) and during leisure time (strenuous exercise) was associated with half the prevalence of moderate-to-complete ED. Our multicultural study demonstrates that in every country studied, high proportions of men older than age 35 have some degree of ED (57-81%). Both severity and prevalence increase consistently with age. Factors associated with ED are similar, but their distribution differs across countries.

Prevalence and correlates of erectile dysfunction in Salvador, northeastern Brazil: a population-based study.

Our objectives were to determine the prevalence of erectile dysfunction (ED) in Brazil and to explore potential sociodemographic, medical, and lifestyle correlates. A cross-sectional, population-based, household survey was conducted in Salvador, Bahia, Brazil. Cluster samples of representative households were randomly selected for interviews. Of 654 eligible subjects, 602 (92%) participated. A structured questionnaire was administered by trained interviewers. ED was categorized as 'none', 'mild', 'moderate', or 'severe' according to the ability to 'attain and/or maintain an erection satisfactory for sexual intercourse'. All data were obtained by self-report. The age-adjusted prevalence of ED was 39.5% (minimal 25.1%, moderate 13.1%, severe 1.3%). Prevalence and severity increased with age. Having never been married, diabetes, depression, or prostate disease and current depressive or lower urinary tract symptoms were significantly (P<0.05) associated with increased prevalence. Medical, sociodemographic, and lifestyle variables associated with ED may alert physicians to patients at risk for ED and offer insight to its etiology.

Prevalence of erectile dysfunction in Colombia, Ecuador, and Venezuela: a population-based study (DENSA).

The purpose of this study was to estimate the prevalence of erectile dysfunction (ED) in Colombia, Ecuador, and Venezuela. A 49-item questionnaire was completed by 1946 men aged 40 years and older. The age-adjusted combined prevalence of minimal, moderate, and complete ED for all three countries was 53.4%, with 19.8% of all men reporting moderate to complete ED. Age was the variable most strongly linked to ED; the prevalence of complete ED increased markedly in men older than 79 y of age (31.9%) and 70-79 y (17.2%) compared with men aged 40-49 y (<3%). Several medical conditions, such as hypertension, benign prostatic hyperplasia, and diabetes, and the use of medications to treat these conditions were correlated with the prevalence of ED. This study corroborates earlier studies demonstrating that ED is very common, increases dramatically with age, and has multiple correlates, including some that are also risk factors for cardiovascular disease.

Relationship between patient self-assessment of erectile dysfunction and the sexual health inventory for men.

BACKGROUND: The Sexual Health Inventory for Men (SHIM) has been shown to possess favorable statistical properties in diagnosing the presence and severity of erectile dysfunction (ED). However, the SHIM has not been compared with patient self-assessment of ED. OBJECTIVE: This article describes an independent-validation study examining the correlation and agreement between the SHIM and patient self-assessment of ED with respect to the severity of ED at baseline and after treatment, and in terms of change from baseline. METHODS: The study population consisted of 247 male outpatients with ED participating in a multicenter, double-blind, placebo-controlled, flexible-dose (25-100 mg/d) Phase IIIb clinical trial in which they were randomized equally to sildenafil citrate or placebo. Patients assessed their degree of ED as severe, moderate, minimal/mild, or no problem at baseline and after 12 weeks of treatment. They also responded to the 5 questions on the SHIM, after which their degree of ED was calculated based on the SHIM total score. RESULTS: In general, the SHIM and the single-item self-assessment question produced similar descriptive profiles of the severity of ED. Kendall tau-b correlations were 0.66 (95% CI, 0.58-0.74) at baseline, 0.86 (95% CI, 0.82-0.90) after treatment, and 0.72 (95% CI, 0.67-0.77) for change from baseline. Agreement between instruments, measured by the weighted kappa statistic, mirrored the correlations at baseline and after treatment. As expected, both measures correlated moderately with improvement in erections and treatment satisfaction of both patient and partner. CONCLUSION: The moderate-to-high correlation and agreement between the SHIM and patient self-assessment of ED validate the SHIM for use in the diagnostic classification of ED severity.

Overall cardiovascular profile of sildenafil citrate.

Sildenafil, a selective inhibitor of phosphodiesterase type 5 (PDE5), is the first in a new class of orally effective treatments for erectile dysfunction. During sexual stimulation, the cavernous nerves release nitric oxide (NO), which induces cyclic guanosine monophosphate (cGMP) formation and smooth muscle relaxation in the corpus cavernosum. Sildenafil facilitates the erectile process during sexual stimulation by inhibiting PDE5 and thus blocking the breakdown of cGMP. Sildenafil alone can cause mean peak reductions in systolic/diastolic blood pressure of 10/7 mm Hg that are not dose related, whereas the heart rate is unchanged. Sildenafil and nitrates both increase cGMP levels in the systemic circulation but at different points along the NO-cGMP pathway. The combination is contraindicated because they synergistically potentiate vasodilation and may cause excessive reductions in blood pressure. Erectile dysfunction is a significant medical condition that shares numerous risk factors with ischemic heart disease, and hence a substantial overlap exists between these patient groups. From extensive clinical trials, the most commonly reported cardiovascular adverse events in patients treated with sildenafil were headache (16%), flushing (10%), and dizziness (2%). The incidences of hypotension, orthostatic hypotension, and syncope and the rate of discontinuation of treatment due to adverse events were <2% and were the same in patients taking sildenafil and those taking placebo. Retrospective analysis of the concomitant use of antihypertensive medications (beta blockers, alpha blockers, diuretics, angiotensin-converting enzyme inhibitors, and calcium antagonists) in patients taking sildenafil did not indicate an increase in the reports of adverse events or significant episodes of hypotension compared with patients treated with sildenafil alone. In clinical trials, the incidence of serious cardiovascular adverse events, including stroke and myocardial infarction, was the same for patients treated with sildenafil or placebo. Concurrent disease states, such as renal or hepatic impairment, or concomitant use of inhibitors of the cytochrome P450 isozyme CYP3A4 could increase systemic exposure to sildenafil. Since the US market launch in April 1998, monitoring of spontaneous adverse event reports in association with sildenafil has demonstrated a pattern that is generally consistent with the experience observed during clinical development, with the exception of infrequent reports of priapism. In conclusion, extensive clinical testing has shown that overall treatment with sildenafil for up to 1 year is well tolerated and is associated with a low incidence of adverse events that result in discontinuation of treatment in <3% of patients.

Serologic testing of cornea donors.

PURPOSE: To review the current requirements and rationale for serologic testing of cornea donors and to provide guidelines for dealing with results of nonrequired tests. METHODS: Eye Bank Association of America (EBAA) and Food and Drug Administration (FDA) regulations are examined with respect to current knowledge of the risk of donor-to-host transmission of systemic infectious diseases via corneal transplantation. RESULTS: Negative screening tests are required for human immunodeficiency virus (HIV) 1 and 2, hepatitis B surface antigen (HBsAg), and hepatitis C virus (HCV) before release of tissue for transplantation. Other tests reported by organ-procurement organizations commonly include hepatitis B core antibody (anti-HBc), syphilis, cytomegalovirus (CMV), and human T-lymphotropic virus (HTLV) I and II. No systemic infectious-disease transmission from donor corneas supplied by EBAA-member eye banks has occurred in the last 12 years, a period during which >400,000 corneas were provided for transplantation. CONCLUSION: EBAA donor-screening requirements, including serologic testing, have resulted in an excellent safety record. Requirements for serologic testing should continue to be regularly reviewed as new information becomes available.