NAION and treatment of erectile dysfunction: reply from Pfizer.
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Carbolines↗
Biomedical subjects
J C Cappelleri
Publications and source records attributed to J C Cappelleri.
Development and validation of the Self-Esteem And Relationship (SEAR) questionnaire in erectile dysfunction.
Development and validation of a patient-reported measure of psychosocial variables in men with erectile dysfunction (ED) is described. Literature review, focus groups, and medical specialists identified 86 potential items. Redundant, ambiguous, or low item-to-total correlation items were removed. Data from 98 men reporting diagnosed ED and 94 controls assisted in final item selection and psychometric evaluation. Treatment responsiveness was evaluated in 93 men with ED in a 10-week open-label trial of sildenafil citrate (Viagra). The 14 chosen items resolved into two domains: Sexual Relationship (eight items) and Confidence (six items), the latter comprising Self-Esteem (four items) and Overall Relationship (two items) subscales. The resulting Self-Esteem And Relationship (SEAR) questionnaire demonstrated validity and reliability. The intervention study demonstrated responsiveness to beneficial treatment with significant improvement in scores (P=0.0001). The SEAR questionnaire possesses strong psychometric properties that support its validity and reliability for measuring sexual relationship, confidence, and particularly self-esteem.
Adult↗
A comparison of the International Index of Erectile Function and erectile dysfunction studies.
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Erectile Dysfunction↗
The International Index of Erectile Function (IIEF): a state-of-the-science review.
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.
Clinical Trials as Topic↗
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.
Adult↗
Treatment satisfaction with inhaled insulin in patients with type 1 diabetes: a randomized controlled trial.
OBJECTIVE: In patients with type 1 diabetes, glycemic control can be achieved as effectively with an inhaled insulin regimen, comprising preprandial inhaled intrapulmonary insulin plus a bedtime ultralente injection, as with a conventional subcutaneous insulin regimen involving two to three injections per day. Our objective was to compare patient satisfaction between inhaled insulin and subcutaneous insulin. RESEARCH DESIGN AND METHODS: Subjects with type 1 diabetes participated in a 12-week open-label trial and were randomized to either an inhaled insulin regimen or a subcutaneous insulin regimen. Subjects (n = 69) were asked to complete a 15-item self-administered satisfaction questionnaire, the Patient Satisfaction with Insulin Therapy (PSIT) Questionnaire, at baseline and week 12. Outcomes included mean percentage changes in global (overall) satisfaction and two subscales: convenience/ease of use and social comfort. RESULTS: The mean percentage improvement in overall satisfaction with inhaled insulin (35.1%, 95% CI 18.0-52.2) was greater than with subcutaneous insulin (10.6%, 4.7-16.5) (P < 0.01), as was the improvement in convenience/ease of use: inhaled insulin 41.3% (22.9-59.6) versus subcutaneous insulin 11.2% (4.1-18.3; P < 0.01). Improvement in social comfort was greater with inhaled insulin but was not statistically significant. The 12-week change in HbA(1c) was associated with improved overall satisfaction (r = -0.27, P = 0.04). CONCLUSIONS: Inhaled insulin may offer the first practical, noninvasive alternative to insulin injections. For patients with type 1 diabetes, inhaled insulin maintains glycemic control and provides greater overall satisfaction and convenience/ease of use than subcutaneous insulin.
Administration, Inhalation↗
Improved detection of differential information-processing speed deficits between two disease-course types of multiple sclerosis.
Patients with multiple sclerosis (MS) frequently demonstrate impairments of information-processing speed (IPS) on measures such as the Paced Auditory Serial Addition Test (PASAT; D. M. A. Gronwall, 1977). The authors have previously shown that their new PASAT scoring method (mean dyad score) is better correlated in comparison with more traditional PASAT scoring method(s), with magnetic resonance imaging measurement of the total area (mm2) of white-matter sclerotic lesions (P. J. Snyder & J. C. Cappelleri, 2001). The present study reports that the mean dyad score discriminated 20 relapsing-remitting MS (RRMS) patients from 15 secondary-progressive MS (SPMS) patients noticeably better than did the standard scoring method(s). Mean dyad scores < 4.13 classified patients as having SPMS with 73% accuracy (sensitivity), whereas scores > or = 4.13 classified patients as having RRMS with 80% accuracy (specificity).
Adult↗
Relationship between patient self-assessment of erectile function and the erectile function domain of the international index of erectile function.
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.
Adult↗
The sexual health inventory for men (IIEF-5): reply to Vroege.
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Adult↗
Development and factor analysis of a questionnaire to measure patient satisfaction with injected and inhaled insulin for type 1 diabetes.
OBJECTIVE: To develop a self-administered questionnaire to address alternative delivery routes of insulin and to investigate aspects of patient satisfaction that may be useful for subsequent assessment and comparison of an inhaled insulin regimen and a subcutaneous insulin regimen. RESEARCH DESIGN AND METHODS: Attributes of patient treatment satisfaction with both inhaled and injected insulin therapy were derived from five qualitative research studies to arrive at a 15-item questionnaire. Each item was analyzed on a five-point Likert scale so that higher item scores indicated a more favorable attitude. There were 69 subjects with type 1 diabetes previously taking injected insulin therapy who were enrolled in a phase II clinical trial. Their baseline responses on the questionnaire were evaluated and subjected to an exploratory factor analysis. Meaningful factors were retained and interpreted based on their psychometric properties. RESULTS: Exploratory factor analysis suggested a two-factor solution accounting for 66 and 20% of the variance, respectively. The first factor contained 10 reliable items (Cronbach's alpha = 0.89) relating to convenience and ease of use, and the second contained 5 reliable items (Cronbach's alpha = 0.82) relating to social comfort. CONCLUSIONS: Among patients with type 1 diabetes, this analysis highlighted and quantified two key factors contributing to patient satisfaction: convenience/ease of use and social comfort. The questionnaire underwent rigorous development, had reliable properties, and an interpretable and rich factor structure. This report is intended to help advance, in subsequent investigations, the understanding and measurement of treatment satisfaction with novel and existing forms of insulin delivery.
Administration, Inhalation↗
[Evidence of the therapeutic effect of antihypertensive therapy: meta-analysis and meta-regression of randomized and controlled trials].
BACKGROUND: Meta-analysis is one of the most useful methodologies in evidence-based medicine. The goal of this paper is to introduce meta-analysis and meta-regression in the synthesis of scientific evidence in the efficacy of antihypertensive therapy. METHODS: Data from 13 randomized controlled trial comparing active antihypertensive therapy with a non-therapeutic control have been analyzed. Data on trials following patients at least more than one year have been poole through random-effects models and meta-regression models. RESULTS: Pooled data from meta-analysis showed that antihypertensive therapy decreased the risk of adverse outcomes attributable to the disease, mainly stroke. Regression models indicated that this risk was independent from study duration and patients mean age. CONCLUSIONS: The results of this study have showed the applicability and usefulness of data synthesis techniques in decision making in health care using hypertension as a case-study. This case-study allows us to make recommendations for research and therapy.
Aged↗
Diagnostic evaluation of the erectile function domain of the International Index of Erectile Function.
OBJECTIVES: To evaluate the erectile function (EF) domain of the International Index of Erectile Function (IIEF) as a diagnostic tool to discriminate between men with and without erectile dysfunction (ED) and to develop a clinically meaningful gradient of severity for ED. METHODS: One thousand one hundred fifty-one men (1035 with and 116 without ED) who reported attempting sexual activity were evaluated using data from four clinical trials of sildenafil citrate (Viagra) and two control samples. The statistical program Classification and Regression Trees was used to determine optimal cutoff scores on the EF domain (range 6 to 30) to distinguish between men with and without ED and to determine levels of ED severity on the EF domain using the IIEF item on sexual intercourse satisfaction. RESULTS: For a 0.5 prevalence rate of ED, the optimal cutoff score was 25, with men scoring less than or equal to 25 classified as having ED and those scoring above 25 as not having ED (sensitivity 0.97, specificity 0.88). Sensitivity analyses revealed a robust statistical solution that was well supported with different assumed prevalence rates and several cross-validations. The severity of ED was classified into five categories: no ED (EF score 26 to 30), mild (EF score 22 to 25), mild to moderate (EF score 17 to 21), moderate (EF score 11 to 16), and severe (EF score 6 to 10). Substantial agreement was shown between these predicted and "true" classes (weighted kappa 0.80). CONCLUSIONS: The EF domain possesses favorable statistical properties as a diagnostic tool, not only in distinguishing between men with and without ED, but also in classifying levels of ED severity. Clinical validation with self-rated assessments of ED severity is warranted.
Erectile Dysfunction↗
Development and evaluation of an abridged, 5-item version of the International Index of Erectile Function (IIEF-5) as a diagnostic tool for erectile dysfunction.
An abridged five-item version of the 15-item International Index of Erectile Function (IIEF) was developed (IIEF-5) to diagnose the presence and severity of erectile dysfunction (ED). The five items selected were based on ability to identify the presence or absence of ED and on adherence to the National Institute of Health's definition of ED. These items focused on erectile function and intercourse satisfaction. For 1152 men (1036 with ED, 116 controls) analyzed, a receiver operating characteristic curve indicated that the IIEF-5 is an excellent diagnostic test. Based on equal misclassification rates of ED and no ED, a cutoff score of 21 (range of scores, 5-25) discriminated best (sensitivity=0.98, specificity=0. 88). ED was classified into five severity levels, ranging from none (22-25) through severe (5-7). Substantial agreement existed between the predicted and 'true' ED classes (weighted kappa=0.82). These data suggest that the IIEF-5 possesses favorable properties for detecting the presence and severity of ED.
Coitus↗
Reply to 'The sexual health inventory for men (IIEF-5)' by JA Vroege.
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Health Status↗
Antipsychotic-induced weight gain: a comprehensive research synthesis.
OBJECTIVE: The purpose of this study was to estimate and compare the effects of antipsychotics-both the newer ones and the conventional ones-on body weight. METHOD: A comprehensive literature search identified 81 English- and non-English-language articles that included data on weight change in antipsychotic-treated patients. For each agent, a meta-analysis and random effects metaregression estimated the weight change after 10 weeks of treatment at a standard dose. A comprehensive narrative review was also conducted on all articles that did not yield quantitative information but did yield important qualitative information. RESULTS: Placebo was associated with a mean weight reduction of 0.74 kg. Among conventional agents, mean weight change ranged from a reduction of 0.39 kg with molindone to an increase of 3.19 kg with thioridazine. Among newer antipsychotic agents, mean increases were as follows: clozapine, 4.45 kg; olanzapine, 4.15 kg; sertindole, 2.92 kg; risperidone, 2.10 kg; and ziprasidone, 0.04 kg. Insufficient data were available to evaluate quetiapine at 10 weeks. CONCLUSIONS: Both conventional and newer antipsychotics are associated with weight gain. Among the newer agents, clozapine appears to have the greatest potential to induce weight gain, and ziprasidone the least. The differences among newer agents may affect compliance with medication and health risk.
Antipsychotic Agents↗
The distribution of body mass index among individuals with and without schizophrenia.
OBJECTIVE: The objective of this study was to estimate and compare the distributions of body mass index (BMI: kg/m2) among individuals with and without schizophrenia, and, thereby, place the weight gain-inducing effects of antipsychotic drugs into context. METHOD: Data sources were (1) the mental health supplement of the 1989 National Health Interview Survey (NHIS; N = 80,130 nonschizophrenic and 150 self-reported schizophrenic individuals), (2) baseline BMI data from a drug trial of the anti-psychotic ziprasidone supplied by Pfizer Inc (420 noninstitutionalized individuals with chronic psychotic disorders [DSM-IV schizophrenia or schizoaffective disorder]) and (3) data from the National Health and Nutrition Examination Survey III (NHANES III; N = 17,689 nonschizophrenic individuals) to act as a control group for the ziprasidone trial data. RESULTS: After age-adjusting BMI in each data set, the NHIS data revealed that men with schizophrenia have mean BMIs similar to those of men without schizophrenia (26.14 vs. 25.63, respectively). In contrast, women with schizophrenia in the NHIS data set had a significantly (p<.001) higher mean BMI than did women without schizophrenia (27.36 vs. 24.50, respectively). Moreover, each decile was higher for women with schizophrenia than for women without schizophrenia. Analysis of the ziprasidone and NHANES III data sets revealed that, on average, men with schizophrenia have mean BMIs comparable to those of men without schizophrenia (26.79 vs. 26.52, respectively). In these 2 data sets, women with schizophrenia also had a mean BMI similar to those of women without schizophrenia (27.29 vs. 27.39, respectively). CONCLUSION: Although there may be a small subpopulation of schizophrenic individuals who are underweight, individuals with schizophrenia were, on the whole, as obese as or more obese than individuals without schizophrenia, suggesting that weight gain induced by antipsychotic agents is an important concern for many individuals.
Antipsychotic Agents↗
An empirical study of the effect of the control rate as a predictor of treatment efficacy in meta-analysis of clinical trials.
If the control rate (CR) in a clinical trial represents the incidence or the baseline severity of illness in the study population, the size of treatment effects may tend to very with the size of control rates. To investigate this hypothesis, we examined 115 meta-analyses covering a wide range of medical applications for evidence of a linear relationship between the CR and three treatment effect (TE) measures: the risk difference (RD); the log relative risk (RR), and the log odds ratio (OR). We used a hierarchical model that estimates the true regression while accounting for the random error in the measurement of and the functional dependence between the observed TE and the CR. Using a two standard error rule of significance, we found the control rate was about two times more likely to be significantly related to the RD (31 per cent) than to the RR (13 per cent) or the OR (14 per cent). Correlations between TE and CR were more likely when the meta-analysis included 10 or more trials and if patient follow-up was less than six months and homogeneous. Use of weighted linear regression (WLR) of the observed TE on the observed CR instead of the hierarchical model underestimated standard errors and overestimated the number of significant results by a factor of two. The significant correlation between the CR and the TE suggests that, rather than merely pooling the TE into a single summary estimate, investigators should search for the causes of heterogeneity related to patient characteristics and treatment protocols to determine when treatment is most beneficial and that they should plan to study this heterogeneity in clinical trials.
Humans↗
Issues in comparisons between meta-analyses and large trials.
CONTEXT: The extent of concordance between meta-analyses and large trials on the same topic has been investigated with different protocols. Inconsistent conclusions created confusion regarding the validity of these major tools of clinical evidence. OBJECTIVE: To evaluate protocols comparing meta-analyses and large trials in order to understand if and why they disagree on the concordance of these 2 clinical research methods. DESIGN: Systematic comparison of protocol designs, study selection, definitions of agreement, analysis methods, and reported discrepancies between large trials and meta-analyses. RESULTS: More discrepancies were claimed when large trials were selected from influential journals (which may prefer trials disagreeing with prior evidence) than from already performed meta-analyses (which may target homogeneous trials) and when both primary and secondary (rather than only primary) end points were considered. Depending on how agreement was defined, kappa coefficients varied from 0.22 (low agreement) to 0.72 (excellent agreement). The correlation of treatment effects between large trials and meta-analyses varied from -0.12 to 0.76, but was more similar (0.50-0.76) when only primary end points were considered. When both the magnitude and uncertainty of treatment effects were considered, large trials disagreed with meta-analyses 10% to 23% of the time. Discrepancies were attributed to different disease risks, variable protocols, quality, and publication bias. CONCLUSIONS: Comparisons of large trials with meta-analyses may reach different conclusions depending on how trials and meta-analyses are selected and how end points and agreement are defined. Scrutiny of these 2 major research methods can enhance our appreciation of both for guiding medical practice.
Bias↗