Biomedical subjects
Publications and source records attributed to R C Rosen.
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PT-141, a cyclic heptapeptide melanocortin analog, was evaluated following intranasal administration in healthy male subjects and in Viagra-responsive erectile dysfunction (ED) patients. Erectile response was assessed by RigiScan trade mark in healthy subjects without visual sexual stimulation (VSS) and in Viagra-responsive ED patients with VSS. In healthy subjects, mean C(max) and AUC((0-t)) increased in a dose-dependent manner. Median T(max) was 0.50 h and mean t(1/2) ranged from 1.85 to 2.09 h. In both studies, an erectile response induced by PT-141 administration was statistically significant, compared to placebo, at doses greater than 7 mg, with the onset of the first erection occurring in approximately 30 min. PT-141 was safely administered and well tolerated in both studies. A maximum-tolerated dose was not identified. Flushing and nausea were the most common adverse events reported in both studies and no clinically significant changes in vital signs, laboratory tests, ECGs, or physical exams were observed. Based upon its erectogenic potential and tolerability profile, PT-141 is a promising candidate for further evaluation as a treatment for male ED.
Erectile dysfunction (ED) is commonly associated with depressed mood and diminished quality of life (QoL), but few studies have investigated the causal associations involved. Therefore, we evaluated the correlation between several measures of mood, QoL, and sexual function in a retrospective analysis of a sample of depressed men (n=152), with ED enrolled in a clinical trial of sildenafil citrate (VIAGRA). Strong correlations were observed at baseline among measures of erectile function (EF), mood, and overall QoL. Significant treatment effects were observed on all three domains, with significant interactions between changes in mood and QoL. Based on multiple regression and path analysis, a model was developed in which EF changes were associated with improved mood and quality of sexual life, which resulted in improved partner satisfaction, family life, and overall life satisfaction. These data suggest that QoL changes associated with ED therapy may be mediated by changes in sexual function, mood, and family relationships.
PT-141, a cyclic heptapeptide melanocortin analog, was evaluated following subcutaneous administration to healthy male subjects and to patients with erectile dysfunction (ED) who report an inadequate response to Viagra. An inadequate response was defined for this study by patient report indicating that achievement of an erection suitable for vaginal penetration occurred < or =50% of the time while taking 100 mg Viagra. Erectile responses were assessed by RigiScan in healthy subjects in the absence of visual sexual stimulation (VSS) and in ED patients in the presence of VSS. Doses ranging from 0.3 to 10 mg were administered to healthy male subjects, resulting in a statistically significant erectile response at doses greater than 1.0 mg. ED patients were treated with placebo, 4 or 6 mg PT-141 in a crossover design in the presence of VSS. The erectile response induced by PT-141 was statistically significant at both doses. PT-141 was safe and well tolerated in both studies. The erectogenic potential of PT-141, its tolerability profile and its ability to cause significant erections in patients who do not have an adequate response to a PDE5 inhibitor suggest that PT-141 may provide an alternative treatment for ED with a potentially broad patient base.
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Explore the source record for details and available documents.
The International Index of Erectile Function (IIEF) is a widely used, multi-dimensional self-report instrument for the evaluation of male sexual function. It is has been recommended as a primary endpoint for clinical trials of erectile dysfunction (ED) and for diagnostic evaluation of ED severity. The IIEF was developed in conjunction with the clinical trial program for sildenafil, and has since been adopted as the 'gold standard' measure for efficacy assessment in clinical trials of ED. It has been linguistically validated in 32 languages and used as a primary endpoint in more than 50 clinical trials. This review summarizes early stages in the psychometric validation of the instrument, its subsequent adoption in randomized clinical trials with sildenafil and other ED therapies, and its use in classifying ED severity and prevalence. The IIEF meets psychometric criteria for test reliability and validity, has a high degree of sensitivity and specificity, and correlates well with other measures of treatment outcome. It has demonstrated consistent and robust treatment responsiveness in studies in USA, Europe and Asia, as well as in a wide range of etiological subgroups. Although only one direct comparator trial has been performed to date, the IIEF is also sensitive to therapeutic effects with treatment agents other than sildenafil. A severity classification for ED has recently been developed, in addition to a brief screening version of the instrument. This review includes the strengths as well as limitations of the IIEF, along with some potential areas for future research.
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STUDY OBJECTIVES: This report describes the construction and validation of a brief self-administered scale to assess sleep knowledge in medical education ("ASKME Survey"). Few measures of this type have been developed previously; none have been validated or widely adopted. The current instrument was designed as a standardized assessment measure for use in medical education in sleep. DESIGN: Instrument was developed in four phases: initial item selection, expert panel review, reliability and construct validity assessment, and final item selection. Content validity was assessed in six general domains: basic sleep principles; circadian sleep/wake regulation; normal sleep architecture; sleep disorders; effects of drugs and alcohol on sleep; and sleep in medical disorders. SETTING: N/A. PARTICIPANTS: Medical students at Robert Wood Johnson Medical School (RWJMS) and University of Kentucky College of Medicine; students in clinical psychology, nursing and other health-related professions at Rutgers University; school nurses at Texas Christian University; practicing physicians; accredited sleep specialists. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Individual item analysis of 30-item survey demonstrated a high degree of discriminant validity. Internal consistency for test items was relatively high (KR-20=0.89). Overall mean percentage correct was highest for accredited sleep specialists (85.3%+/-10.8%) and lowest for school nurses (53.1%+/-13.7%). Significant group differences were observed across all question categories (p < 0.0001). Medical students scored significantly higher than the nurses on questions related to sleep architecture (59.5% vs. 42.5%) and narcolepsy (36.4% vs. 21.3%). CONCLUSIONS: "ASKME" demonstrates a high degree of internal consistency and reliability among survey items. It discriminates between samples with varied levels of education, experience, and specialty training. The survey is currently available via the American Academy of Sleep Medicine website (http://www.aasmnet.org).
Measurement approaches for male and female sexual dysfunction have proliferated in recent years, spurred in large part by the development of new treatments for male and female dysfunction. In the past, physiologic measures of penile tumescence and rigidity in males, and vaginal blood flow in females, played an important role in clinical and research studies. More recently, a variety of brief, self-report measures have been developed for assessing male and female function across a variety of sexual domains (eg, desire, arousal, orgasm, satisfaction). These self-report measures have been shown to have a high degree of reliability and validity, and are sensitive to treatment interventions. Accordingly, they are widely employed in clinical trials. Daily diary or sexual event logs have similarly been developed for this purpose. Self-report measures have been used for clinical screening purposes and for diagnostic assessment of sexual function in a number of studies. Finally, several disease-specific quality of life and treatment satisfaction measures have been developed, which are currently in widespread use in clinical trials of sexual dysfunction.
Psychogenic factors are involved alone or in combination with organic causes in a substantial number of cases of erectile dysfunction. Epidemiologic studies have implicated the role of depressed mood, loss of self-esteem, and other psychosocial stresses in the cause of erectile dysfunction. A new definition and classification of psychogenic erectile dysfunction has been proposed based on recent clinical and research findings. According to this new classification, psychogenic erectile dysfunction is categorized as generalized or situational type, with subcategories of each type proposed. Traditional treatment approaches for psychogenic erectile dysfunction have included anxiety reduction and desensitization procedures, cognitive-behavioral interventions, guided sexual stimulation techniques, and couples' or relationship counseling. Recently, these approaches increasingly have been combined with pharmacologic therapy such as sildenafil. Special situations have been identified in which combining psychosocial interventions with medical therapy is recommended. These situations include problems of sexual initiation, low sexual desire, other sexual dysfunctions, and significant couples' or relationship problems. More research is needed on the role of psychosocial interventions in the treatment of erectile dysfunction.
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.
IC351 (Cialis) is a selective inhibitor of PDE5. The efficacy and safety of on-demand dosing of IC351 in men with erectile dysfunction was assessed in a multicenter, double-blind, placebo-controlled study. One hundred seventy-nine men (mean age: 56 y) were randomized to receive placebo or IC351 at doses of 2, 5, 10 or 25 mg, taken on demand over a 3-week period. The primary endpoints were change from baseline in responses to Questions 3 (Q3) and 4 (Q4) of the International Index of Erectile Function (IIEF). IC351 significantly improved IIEF Q3 scores at all doses vs placebo (P < or =0.003). IC351 also significantly improved IIEF Q4 scores in all but the 2 mg group (P < or =0.0003). No significant changes in laboratory values, ECGs, or blood pressure were observed. The most common adverse events were headache and dyspepsia. The conclusion of this study was that on-demand IC351 at doses up to 25 mg was well tolerated and significantly improved erectile function.
OBJECTIVE: Depressed men commonly have erectile dysfunction, and men with erectile dysfunction are frequently depressed. Since the etiologic and modulatory relationships between depression and erectile dysfunction have been poorly characterized, a 12-week, randomized, double-blind, placebo-controlled trial was conducted at 20 urologic clinics to evaluate the effects of sildenafil treatment in men with erectile dysfunction and mild-to-moderate comorbid depressive illness. METHOD: Men (N=152, mean age=56 years) with erectile dysfunction for > or =6 months (mean=5.7 years), a DSM-IV diagnosis of depressive disorder not otherwise specified, and a Hamilton Depression Rating Scale score > or =12 (mean at baseline=16.9) were randomly assigned to flexible-dose treatment with sildenafil citrate or matching placebo. Interviewer-rated and self-report instruments were used to assess changes in sexual function, depressive symptoms, and quality of life. Conservative criteria were used to classify erectile dysfunction treatment response and nonresponse. RESULTS: Sildenafil was strongly associated with erectile dysfunction treatment response. Fifty-eight men met the conservative criteria for response (48 given sildenafil, 10 given placebo), and 78 men did not respond (18 given sildenafil, 60 given placebo). Mean decreases of 10.6 and 2.3 in Hamilton depression scale scores were seen in treatment responders and nonresponders, respectively; 76% of treatment responders showed a > or =50% decline in Hamilton depression scale score versus 14% of nonresponders. Quality of life was similarly improved in treatment responders. CONCLUSIONS: Sildenafil is efficacious for erectile dysfunction in men with mild-to-moderate depressive illness. Improvement of erectile dysfunction is associated with marked improvement in depressive symptoms and quality of life.
BACKGROUND: The ovaries provide approximately half the circulating testosterone in premenopausal women. After bilateral oophorectomy, many women report impaired sexual functioning despite estrogen replacement. We evaluated the effects of transdermal testosterone in women who had impaired sexual function after surgically induced menopause. METHODS: Seventy-five women, 31 to 56 years old, who had undergone oophorectomy and hysterectomy received conjugated equine estrogens (at least 0.625 mg per day orally) and, in random order, placebo, 150 microg of testosterone, and 300 microg of testosterone per day transdermally for 12 weeks each. Outcome measures included scores on the Brief Index of Sexual Functioning for Women, the Psychological General Well-Being Index, and a sexual-function diary completed over the telephone. RESULTS: The mean (+/-SD) serum free testosterone concentration increased from 1.2+/-0.8 pg per milliliter (4.2+/-2.8 pmol per liter) during placebo treatment to 3.9+/-2.4 pg per milliliter (13.5+/-8.3 pmol per liter) and 5.9+/-4.8 pg per milliliter (20.5+/-16.6 pmol per liter) during treatment with 150 and 300 microg of testosterone per day, respectively (normal range, 1.3 to 6.8 pg per milliliter [4.5 to 23.6 pmol per liter]). Despite an appreciable placebo response, the higher testosterone dose resulted in further increases in scores for frequency of sexual activity and pleasure-orgasm in the Brief index of Sexual Functioning for Women (P=0.03 for both comparisons with placebo). At the higher dose the percentages of women who had sexual fantasies, masturbated, or engaged in sexual intercourse at least once a week increased two to three times from base line. The positive-well-being, depressed-mood, and composite scores of the Psychological General Well-Being Index also improved at the higher dose (P=0.04, P=0.03, and P=0.04, respectively, for the comparison with placebo), but the scores on the telephone-based diary did not increase significantly. CONCLUSIONS: In women who have undergone oophorectomy and hysterectomy, transdermal testosterone improves sexual function and psychological well-being.
OBJECTIVES: To assess the validity of severity classes on the erectile function (EF) domain of the International Index of Erectile Function by determining their relationship with the self-assessment of EF, before and after treatment, in an independent cohort of patients. METHODS: Two hundred forty-seven men with clinically diagnosed erectile dysfunction (ED) and in a stable heterosexual relationship were enrolled in a randomized, double-blind, multicenter, placebo-controlled, parallel-group, 12-week, flexible-dose study. Patients assessed their degree of ED as severe, moderate, minimal/mild, or no problem at baseline and after treatment. They also responded to the six questions of the EF domain, with the total score indicating the following degrees of ED: severe, EF score 1 to 10; moderate, EF score 11 to 16; mild to moderate, EF score 17 to 21; mild, EF score 22 to 25; and no ED, EF score 26 to 30. Descriptive profiles of the two diagnostic instruments were compared. The correlations between the instruments were evaluated with Kendall's tau-b at baseline, after treatment at 12 weeks, and at change from baseline. RESULTS: The two measures gave generally similar descriptive profiles of ED severity. The correlations were 0. 65 (95% confidence interval 0.57 to 0.73) at baseline, 0.86 (95% confidence interval 0.83 to 0.89) after 12 weeks of treatment, and 0. 73 (95% confidence interval 0.67 to 0.79) at change from baseline. CONCLUSIONS: The moderate-to-high correlation between the patients' self-assessment of EF and the EF domain of the International Index of Erectile Function provides a validation of this domain for the reliable diagnostic classification of ED severity.
Sexual dysfunction is highly prevalent in both sexes and adversely affects patients' quality of life and well being. Given the frequent association between sexual dysfunction and cardiovascular disease, in addition to the potential cardiac risk of sexual activity itself, a consensus panel was convened to develop recommendations for clinical management of sexual dysfunction in patients with cardiovascular disease. Based upon a review of the research and presentations by invited experts, a classification system was developed for stratification of patients into high, low, and intermediate categories of cardiac risk. The large majority of patients are in the low-risk category, which includes patients with (1) controlled hypertension; (2) mild, stable angina; (3) successful coronary revascularization; (4) a history of uncomplicated myocardial infarction (MI); (5) mild valvular disease; and (6) no symptoms and <3 cardiovascular risk factors. These patients can be safely encouraged to initiate or resume sexual activity or to receive treatment for sexual dysfunction. An important exception is the use of sildenafil in patients taking nitrates in any form. Patients in the intermediate-risk category include those with (1) moderate angina; (2) a recent MI (<6 weeks); (3) left ventricular dysfunction and/or class II congestive heart failure; (4) nonsustained low-risk arrhythmias; and (5) >/=3 risk factors for coronary artery disease. These patients should receive further cardiologic evaluation before restratification into the low- or high-risk category. Finally, patients in the high-risk category include those with (1) unstable or refractory angina; (2) uncontrolled hypertension; (3) congestive heart failure (class III or IV); (4) very recent MI (<2 weeks); (5) high-risk arrhythmias; (6) obstructive cardiomyopathies; and (7) moderate-to-severe valvular disease. These patients should be stabilized by specific treatment for their cardiac condition before resuming sexual activity or being treated for sexual dysfunction. A simple algorithm is provided for guiding physicians in the management of sexual dysfunction in patients with varying degrees of cardiac risk.