RESUMEN
The prescribing information for sildenafil citrate (VIAGRA, Pfizer, New York, NY, USA) recommends flexible dosing (50 mg initially, adjusted to 100 or 25 mg based on effectiveness and tolerability) in most men with erectile dysfunction (ED). In many men, however, 100 mg may be the most appropriate initial dose because it would reduce the need for titration and could prevent discouragement and treatment abandonment should 50 mg be insufficient. Results of two previously published double-blind, placebo-controlled sildenafil trials of similar design except for a fixed-dose vs flexible-dose regimen were analyzed. Relative to the flexible-dose, approximately one-third more men were satisfied with an initial and fixed dose of 100 mg. In addition, tolerability was similar, and improvements from baseline in outcomes on validated, ED-specific, patient-reported questionnaires were either similar (erectile function and the percentage of completely hard and fully rigid erections) or greater (emotional well-being and the overall sexual experience). The similarity in outcomes is not surprising given that almost 90% of the men in the flexible-dose trial titrated to 100 mg after 2 weeks. These data suggest prescription of an initial dose of 100 mg for men with ED, except in those for whom it is inappropriate.
Asunto(s)
Emociones , Disfunción Eréctil/tratamiento farmacológico , Satisfacción del Paciente , Erección Peniana/fisiología , Erección Peniana/psicología , Piperazinas/administración & dosificación , Sulfonas/administración & dosificación , Adulto , Coito/psicología , Método Doble Ciego , Disfunción Eréctil/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Orgasmo/fisiología , Piperazinas/efectos adversos , Placebos , Purinas/administración & dosificación , Purinas/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Citrato de Sildenafil , Sulfonas/efectos adversos , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To determine the risk-benefit ratio of a forced dose-escalation regimen (2 to 3 to 4 mg) in a European clinical study evaluating apomorphine sublingual (SL) in treating erectile dysfunction (ED), by evaluating the overall tolerability and efficacy of the regimen compared with placebo in patients with ED, and evaluating efficacy by assessing the proportion of successful attempts resulting in sexual intercourse. PATIENTS AND METHODS: This randomized, double-blind, two-arm, parallel-group study was conducted in 507 patients enrolled at 34 European sites. After a 1-2 week screening period, patients were treated for 8 weeks with either placebo or apomorphine SL administered as a forced dose-escalation regimen. Heterosexual men (aged 18-70 years) were eligible for participation in the study if they were in stable health, a stable relationship of > or = 6 months duration, had a history of erectile inability, and were diagnosed with ED (successful in fewer than half of attempts to attain and maintain an erection firm enough for intercourse during the 30 days before screening). Patients provided information (recorded on diary cards and reviewed at each study visit) about the frequency and success in achieving erections and of sexual intercourse attempts during both the screening and treatment periods. The dosing regimen required patients to take one tablet of apomorphine SL (2 mg for 2 weeks, then 3 mg for 2 weeks and finally 4 mg for the remaining 4 weeks) or placebo 15-25 min before intercourse, and intercourse was to be attempted at least twice a week. Safety data were collected throughout the 8-week study period, and included recording adverse events, vital signs and changes in laboratory test values for standard haematology and biochemistry variables. The primary efficacy variable was the proportion of successful attempts, defined as an erection rigid enough for sexual intercourse, occurring after dosing (successful intercourse rate). The proportion of erections achieved was a secondary efficacy variable. RESULTS: Of the 507 patients, 254 received apomorphine SL and 253 received placebo; 87% of patients in both groups completed the 8-week treatment period. Of the patients receiving apomorphine SL, 24% had hypertension, 11% had coronary artery disease, 10% had diabetes, and 5.5% had benign prostatic hypertrophy; 62.6% of treated patients received concomitant medications for these maladies. The treatment groups were balanced for demographic and baseline variables, including comorbidity factors. Treatment-emergent adverse events, reported by > 5% of patients in the treated group, were nausea (9.8%), dizziness (7.1%) and headache (6.7%), compared with 0.4%, 2.4% and 4.0%, respectively, in the placebo group. Sixty-six patients withdrew from the study, 16 because of study drug-related adverse events (12 from the apomorphine and four from the placebo group). Six patients (three in each group) reported a total of nine serious treatment-emergent adverse events, all of which resolved by the end of the study. In the intention-to-treat population, the proportion of successful attempts at sexual intercourse and of erections were statistically greater in the apomorphine than in the placebo group (P = 0.001 and 0.021, respectively); analysis of the per-protocol population results confirmed this significant difference. CONCLUSION: This European study supports the safety and tolerability of apomorphine SL despite the forced escalation to a 4-mg dose (exceeding the approved 2-3 mg dose). Adverse effects were not treatment-limiting. These results further support the clinically significant efficacy of apomorphine SL for treating ED at all doses used. The risk/benefit ratio supports apomorphine SL as a safe and effective alternative in managing ED.
Asunto(s)
Apomorfina/administración & dosificación , Agonistas de Dopamina/administración & dosificación , Disfunción Eréctil/tratamiento farmacológico , Administración Sublingual , Adolescente , Adulto , Anciano , Apomorfina/efectos adversos , Agonistas de Dopamina/efectos adversos , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Europa (Continente) , Humanos , Masculino , Persona de Mediana Edad , Comprimidos , Resultado del TratamientoRESUMEN
BACKGROUND: The aim of this study was to study the value of diagnostic laparoscopy prospectively in fertile women scheduled for acute appendectomy. METHODS: For this study, 110 women, with acute abdominal pain ages 15 to 47 years, in whom the surgeon had decided to perform an appendectomy, were randomized to either open appendectomy or diagnostic laparoscopy, then open appendectomy if necessary. RESULTS: Appendicitis was diagnosed in 66% of the women after open surgery, and in 73% after laparoscopy. During laparoscopy, was appendicitis misdiagnosed in only 7% of the women, from whom the appendix unnecessarily removed, whereas 34% in the open surgery group had a healthy appendix removed. No appendicitis was missed in the laparoscopic group. The relative risk of removing a healthy appendix in open surgery was 6.6 relative risk (range, 2-21 C.I.) as compared with laparoscopy. Among the women with a healthy appendix, a gynecologic diagnosis was found in 73% after laparoscopy, as compared with 17% after open surgery. CONCLUSIONS: Laparoscopy reduces unnecessary appendectomies and improves diagnosis in fertile women.