Addition of alendronate to ongoing hormone replacement therapy in the treatment of osteoporosis: a randomized, controlled clinical trial.

Alendronate and estrogen are effective therapies for postmenopausal osteoporosis, but their efficacy and safety as combined therapy are unknown. The objective of this study was to evaluate the addition of alendronate to ongoing hormone replacement therapy (HRT) in the treatment of postmenopausal women with osteoporosis. A total of 428 postmenopausal women with osteoporosis, who had been receiving HRT for at least 1 yr, were randomized to receive either alendronate (10 mg/day) or placebo. HRT was continued in both groups. Changes in bone mineral density (BMD) and biochemical markers of bone turnover were assessed. Compared with HRT alone, at 12 months, alendronate plus HRT produced significantly greater increases in BMD of the lumbar spine (3.6% vs. 1.0%, P < 0.001) and hip trochanter (2.7% vs. 0.5%, P < 0.001); however, the between-group difference in BMD at the femoral neck was not significant (1.7% vs. 0.8%, P = 0.072). Biochemical markers of bone turnover (serum bone-specific alkaline phosphatase and urine N-telopeptide) decreased significantly at 6 and 12 months with alendronate plus HRT, and they remained within premenopausal levels. Addition of alendronate to ongoing HRT was generally well tolerated, with no significant between-group differences in upper gastrointestinal adverse events or fractures. This study demonstrated that, in postmenopausal women with low bone density despite ongoing treatment with estrogen, alendronate added to HRT significantly increased bone mass at both spine and hip trochanter and was generally well tolerated.

An open multicenter long-term treatment evaluation of Sinemet CR. Sinemet CR Multicenter Study Group.

The safety and efficacy of Sinemet CR were studied in an open-label, 52-week trial. The study was completed by 156 mildly to moderately ill Parkinson's patients (primarily Hoehn and Yahr stage II to III) at 10 sites. Patients had their treatment optimized on standard Sinemet prior to beginning Sinemet CR treatment. Following titration, there was a median reduction in dosing frequency of 25% (from 4.1 to 3.2 doses/day) relative to the standard Sinemet baseline. Total daily levodopa dosage increased from 623 to 808 mg/day (+33%), a factor consistent with the lower bioavailability of the controlled-release formulation. Mean efficacy scores on the New York University Parkinson's Disease Scale decreased from 7.4 at the end of baseline to 5.8 at 12 weeks, a decline of 20%. The scores remained at this level throughout 52 weeks of treatment. At the end of 1 year of treatment, 60% of patients rated themselves as improved, while physicians rated 64% of the patients as improved. Adverse experiences were similar to those reported by patients taking standard levodopa preparations. Two thirds of the reported adverse experiences occurred within the 1st 3 months of Sinemet CR therapy, indicating that increased length of exposure to Sinemet CR was not associated with an increasing incidence of adverse experiences.

Multicenter controlled study of Sinemet CR vs Sinemet (25/100) in advanced Parkinson's disease.

Controlled-release carbidopa/levodopa 50/200 (Sinemet CR) and standard carbidopa/levodopa (Sinemet 25/100) were compared in a multicenter double-blind trial involving 202 patients with advanced Parkinson's disease and motor response fluctuations. Treatment with Sinemet CR significantly reduced daily "off" time. According to both physician and patient global ratings, patients showed significant improvements with Sinemet CR compared to treatment with standard Sinemet. Patients preferred Sinemet CR treatment by a ratio of approximately 2 to 1. Daily dosing frequency was 33% less with Sinemet CR, while daily intake of levodopa required was increased by 25%. The safety profiles of the 2 formulations were similar. We conclude that Sinemet CR is superior to standard Sinemet for many patients with advanced Parkinson's disease, although it does not solve the problem of fluctuating motor performance.

Comparison of the effects on quality of life and of the efficacy and tolerability of lovastatin versus pravastatin. The Quality of Life Multicenter Group.

This multicenter study compared the effects of lovastatin (40 mg) and pravastatin (40 mg) on quality of life. Men, aged 20 to 65 years old, with primary hypercholesterolemia (types IIa and IIb) were eligible for enrollment if baseline low-density lipoprotein cholesterol met the first National Cholesterol Education Program adult treatment guidelines. Eligible patients were enrolled into a 6-week diet baseline period, followed by a 6-week diet-plus-placebo period. Patients whose low-density lipoprotein cholesterol still met National Cholesterol Education Program guidelines for drug therapy were randomized into the double-blind, active-treatment period to receive either lovastatin 40 mg or pravastatin 40 mg/day for 12 weeks. Clinic visits were scheduled every 4 weeks and included complete serum lipid profiles, monitoring of adverse experiences, and patient completion of health-related quality-of-life questionnaires. The primary end point of the study was the change in quality of life, as measured by the Nottingham Health Profile (part 1) after 12 weeks of treatment. Secondary end points included responses to a general health question from the National Health and Nutrition Examination Survey, sexual function questions from the Medical Outcomes Study, and stress/life event questions from the National Institutes of Health Post-Coronary Artery Bypass Grafting Study. No significant differences between the 2 groups were observed in tolerability, health-related quality-of-life measures, or changes in lipid profiles.

Efficacy and tolerability of finasteride in symptomatic benign prostatic hyperplasia: a primary care study. Primary Care Investigator Study Group.

Because increasing numbers of men are seeking treatment for benign prostatic hyperplasia (BPH) from primary care physicians, we sought to assess the efficacy and tolerability of finasteride in a primary care setting. In this randomized, double-masked study, 2,112 men with symptomatic BPH received either finasteride (n = 1,589) or placebo (n = 523) for 1 year. At 3, 6, 9, and 12 months, urinary symptoms were measured using the American Urological Association Symptom Index (AUASI). Quality of life was assessed using the BPH Impact Index (BII), which assessed bother, worry, physical discomfort, and restriction in activities. Both patients and investigators assessed overall urologic status. Investigators assessed the effect of the drug on plasma lipids in a subset of patients. Patients treated with finasteride had a statistically significant mean decrease in AUASI scores compared with patients treated with placebo beginning at month 6 and continuing throughout the study. At month 12, adjusted mean decreases in AUASI scores were -4.96 for finasteride versus -3.71 for placebo. Statistically significant differences in favor of finasteride were also noted on BII at months 9 and 12. Patient and investigator overall assessments showed greater improvement in the finasteride group beginning at month 6. The incidence of drug-related sexual adverse experiences was significantly greater in finasteride-treated patients but led to withdrawal in only 2.2% of these patients. Overall lipid profile was not significantly altered in either group. Based on improvement in symptoms and quality of life, and on its favorable tolerability profile, finasteride should be considered by primary care physicians for management of symptomatic BPH.

Efficacy, tolerability, and effect on health-related quality of life of finasteride versus placebo in men with symptomatic benign prostatic hyperplasia: a community based study. CUSP Investigators. Community based study of Proscar.

This study sought to assess the efficacy, tolerability, and effect of finasteride on health-related quality of life (HRQL) in a diverse population of men with moderate-to-severe symptomatic benign prostatic hyperplasia (BPH). This double-blind study evaluated finasteride and placebo for 12 months in 2342 men with BPH (16.2% black, 14.5% Hispanic, 69.3% Caucasian/other) in a community-based setting. At 3-month intervals, urinary symptoms were measured by use of the American Urologic Association symptom index. HRQL was assessed by use of the BPH impact index (BII), which evaluated degree of bother, worry, physical discomfort, and restriction in activities as a result of urinary symptoms. Additional questions regarding activities of living were administered, and global assessments of change in urologic status were performed by both patients and investigators. Compared with placebo, patients treated with finasteride had a statistically significant decrease in symptom scores when first measured at month 3. Symptom scores continued to improve in finasteride-treated patients throughout the study; at month 12, the mean decrease in symptom scores in the finasteride-treated patients was -4.8 compared with -3.4 for placebo patients ( P = 0.0001). Statistically significant differences in favor of finasteride also were noted at month 12 on the BII (P = 0.0465), and finasteride-treated patients experienced less interference with activities of living (P = 0.0518). Patient and investigator global assessments of urologic status showed that significantly more patients in the finasteride group considered themselves improved and were considered improved by investigators at month 12 (P = 0.000). Finasteride was generally well tolerated. The incidence of drug-related sexual adverse experiences was significantly higher in the finasteride group (P = 0.000), but led to withdrawal in only 1.5% of patients. The demonstrated efficacy and tolerability of finasteride in reducing symptoms and improving quality of life confirm observations of previous trials and make finasteride a highly desirable treatment option for many men with symptomatic BPH.

Combined analysis of two multicenter studies of finasteride 5 mg in the treatment of symptomatic benign prostatic hyperplasia.

The purpose of this paper is to examine effects of finasteride 5 mg across different age groups in an ethnically diverse population of men with symptomatic benign prostatic hyperplasia (BPH) seen in community urology and primary care practices. Data were combined from two previous placebo-controlled randomised trials of finasteride that evaluated changes in urinary symptoms, blinded global assessments of urologic status, adverse experiences, and effects on dihydrotestosterone (DHT) and prostate-specific antigen (PSA) in over 4500 men. Finasteride showed a favourable efficacy and tolerability profile in this large ethnically diverse population and was similarly effective in middle-aged and older men with BPH and prostate gland enlargement.

The American Urological Association symptom index: does mode of administration affect its psychometric properties?

PURPOSE: We determine whether self-administration and interviewer administration of the American Urological Association (AUA) symptom index are equivalent. MATERIALS AND METHODS: The AUA symptom index was administered twice to 41 visually impaired or illiterate men. Men who were able were randomized to self-administration first and then interviewer administration (43) or the reverse (40). RESULTS: The scores in each group were reliable. However, because we could not reject a differential carryover effect, the nonsignificant test of mode effect in the crossover design may have been invalid. At time 1 there was no significant difference between group mean scores for randomized patients (p = 0.13). CONCLUSIONS: Although the AUA symptom index should be self-administered when possible, interviewer administration appears to be acceptable.

Effects of finasteride on health-related quality of life in men with symptomatic benign prostatic hyperplasia. Finasteride Study Group.

The effects of urinary symptoms on health-related quality of life (HRQL) are important in therapeutic decision making. Few have evaluated the treatment effects on HRQL in men with benign prostatic hyperplasia (BPH), even though increased urinary symptoms are associated with greater worry, bother, and interference with living activities. We report on patient assessments of such disease-specific measures as well as general HRQL measures from two placebo-controlled clinical trials of finasteride in the treatment of symptomatic BPH. Patients treated with finasteride appeared to have greater improvement than placebo-treated patients in disease-specific measures and in patient global assessment. The treated group appeared to have a greater mean increase in sexual domain scores. As expected, general measures (health rating, life satisfaction, ladder of life) changed little. Thus, treatment with finasteride appears to reduce bother, worry, and activity interference due to symptoms but in a small percentage of men may lead to slightly reduced sexual function.

Enalapril and hydrochlorothiazide as antihypertensive agents in the elderly.

This randomized, double blind study compared the antihypertensive effects of enalapril to hydrochlorothiazide (HCTZ) in the elderly. One hundred seventy-four patients with diastolic blood pressures (DBP) of 90-120 mm Hg or isolated systolic hypertension (ISH) (systolic BP greater than 160 mm Hg and diastolic BP less than 90 mm Hg) were studied. After four weeks of placebo, patients received either enalapril 10 mg or HCTZ 12.5 mg once daily. If the BP was uncontrolled (DBP greater than 85 mm Hg or SBP greater than 140 mm Hg) after 4 weeks, the dose was doubled. At 8 weeks, if necessary, the other drug could be added at the lower dose, then doubled 4 weeks later. Two-thirds of the patients had essential hypertension (EH), the rest ISH; 68% were male and 80% Caucasian. The baseline BPs were 167/94 mm Hg in both groups, at 8 weeks the mean BPs were 148/85 mm Hg in both groups (p less than or equal to 0.01), and at the end of the study the BPs with enalapril were 144/83 mm Hg and with HCTZ they were 145/83 mm Hg (p less than or equal to 0.01). The Caucasians showed greater BP falls on enalapril than HCTZ after 4 weeks (p less than or equal to 0.05). The SBP falls for the ISH (-22 mm Hg) and EH (-23 mm Hg) groups were similar at the end of the study. Both drugs were generally well tolerated. Laboratory adverse experiences (AEs) were 9% more common in the HCTZ patients (n.s.). Enalapril and HCTZ both seem to be effective antihypertensive agents in the elderly.

Randomized, double-blind comparison of famotidine with ranitidine in treatment of acute, benign gastric ulcer disease. Community-based study coupled with a patient registry.

A multicenter, double-blind, randomized controlled trial comparing the efficacy and safety of famotidine with ranitidine in the treatment of acute, benign gastric ulcer disease was coupled with a community-based gastric ulcer disease registry. One hundred ninety-five patients with endoscopically documented gastric ulcer disease were enrolled in the trial and randomly allocated to treatment with either famotidine 40 mg at bedtime or ranitidine 150 mg twice a day. Healing rates were similar in both groups: at four weeks 49% vs 48%, at six weeks 71% vs 69%, and at eight weeks 83% vs 81% for famotidine and for ranitidine, respectively. Pain relief, antacid tablet use, and adverse experiences were also similar in the two groups. Only 25% of patients entered in the gastric ulcer registry were enrolled in the trial. Given that patients with more severe or complicated gastric ulcer disease should be excluded from controlled trials of new drugs, the screening criteria used in the present study be excluded from findings being representative of a quarter of the patients seen in these practices. Therefore, coupling a patient registry with a clinical trial helps determine the applicability of its results. Famotidine 40 mg at bedtime is an effective and well-tolerated treatment of acute, benign gastric ulcer disease and is comparable in efficacy and safety to ranitidine 150 mg twice a day.