The effects of combination therapy with dutasteride plus tamsulosin on clinical outcomes in men with symptomatic BPH: 4-year post hoc analysis of European men in the CombAT study.

CombAT (Combination of Avodart and Tamsulosin) was a randomised, double-blind study in men (n=4844) aged ≥ 50 years with a clinical diagnosis of BPH. Patients were randomised to daily tamsulosin 0.4 mg, dutasteride 0.5 mg or both for 4 years. The primary endpoint was time to acute urinary retention (AUR) or BPH-related surgery. Secondary endpoints included BPH clinical progression, symptoms and maximum urinary flow rate. A post hoc analysis of data from the European subgroup was conducted. A total of 2925 men were randomised to treatment in Europe as part of CombAT (tamsulosin, n=972; dutasteride, n=970; combination, n=983). Combination therapy significantly reduced the relative risk of AUR or BPH-related surgery compared with either monotherapy at 4 years, and also significantly reduced the risk of BPH clinical progression. Combination therapy also provided significantly greater symptom improvement than either monotherapy at 4 years. Safety and tolerability of dutasteride plus tamsulosin was consistent with previous experience of this combination and with the monotherapies. These data provide further evidence to support the use of long-term combination therapy (dutasteride plus tamsulosin) in men with moderate-to-severe lower urinary tract symptoms because of BPH and prostatic enlargement. The results in the European subgroup are generally consistent with those in the overall study population.

Effect of dutasteride, tamsulosin and the combination on patient-reported quality of life and treatment satisfaction in men with moderate-to-severe benign prostatic hyperplasia: 4-year data from the CombAT study.

OBJECTIVE: To investigate the effect of combination therapy with dutasteride plus tamsulosin compared with each monotherapy on patient-reported health outcomes over 4 years in men with moderate-to-severe lower urinary tract symptoms (LUTS) because of benign prostatic hyperplasia (BPH). METHODS: CombAT was a 4-year international, double-blind, randomised, parallel-group trial in men (n = 4844) with moderate-to-severe symptoms of BPH and at increased risk of disease progression [age > or = 50 years, International Prostate Symptom Score (IPSS) > or = 12, prostate volume > or = 30 cc, serum prostate-specific antigen > or = 1.5 ng/ml to < or = 10 ng/ml and maximum urinary flow rate 5-15 ml/s with minimum voided volume > or = 125 ml]. Subjects were randomised to receive 0.5 mg dutasteride, 0.4 mg tamsulosin or the combination once daily for 4 years. The primary endpoint at 4 years was the time to event and proportion of subjects with acute urinary retention or undergoing BPH-related prostate surgery. Secondary endpoints included the health-outcomes measures, BPH Impact Index (BII), IPSS question 8 (IPSS Q8) and the Patient Perception of Study Medication (PPSM) questionnaire. RESULTS: At 4 years, combination therapy resulted in significantly superior improvements from baseline in BII and IPSS Q8 than either monotherapy; these benefits were observed from 3 months onwards compared with dutasteride and from 9 months (BII) or 12 months (IPSS Q8) onwards compared with tamsulosin. Also at 4 years, the PPSM questionnaire showed that a significantly higher proportion of patients was satisfied with, and would request treatment with, combination therapy compared with either monotherapy. CONCLUSIONS: Combination therapy (dutasteride plus tamsulosin) provides significantly superior improvements in patient-reported quality of life and treatment satisfaction than either monotherapy at 4 years in men with moderate-to-severe BPH symptoms.

Efficacy and safety of dutasteride, tamsulosin and their combination in a subpopulation of the CombAT study: 2-year results in Asian men with moderate-to-severe BPH.

Although ethnicity-based differences in prostate size and physiology have been reported, results of benign prostatic hyperplasia (BPH) treatment trials in predominantly Caucasian patients are assumed to be applicable to non-Caucasian populations. This post hoc analysis investigated whether an Asian subpopulation of men with moderate-to-severe BPH in the CombAT study achieves treatment responses in line with those of the overall study population. In this double-blind, randomized, parallel-group trial, 325 Asian men were assigned to treatment with 0.5 mg dutasteride once daily, 0.4 mg tamsulosin once daily or the combination. Decrease in international prostate symptom score (IPSS) at month 24 from baseline (the primary endpoint) was significantly greater with combination treatment compared with tamsulosin (P<0.05), and numerically, but not statistically significantly, greater compared with dutasteride. Mean IPSS was reduced from baseline by 7.5 (+/-0.84) in the combination group, by 6.3 (+/-0.86) in the dutasteride group and by 4.5 (+/-0.78) in the tamsulosin group, resulting in respective mean IPSS at months 24 of 11.4 (+/-0.60), 12.7 (+/-0.70) and 14.3 (+/-0.74). The adverse event profile was similar to that observed in the overall CombAT population, and drug-related adverse events were more common with combination therapy (26%) than with tamsulosin (15%) or dutasteride (9%). No unexpected adverse events emerged. In conclusion, in Asian men with moderate-to-severe lower urinary tract symptoms and an enlarged prostate, combination therapy achieved significantly greater improvements from baseline BPH symptoms, flow rate, quality of life, reduced prostate volume and improved treatment satisfaction compared with tamsulosin monotherapy.

Computer-assisted training for improving wheelchair mobility in unilateral neglect patients.

OBJECTIVE: To investigate whether a computer-assisted training (CAT) program for patients with left unilateral neglect would decrease symptoms of this disorder. DESIGN: Case-control study. SETTING: Inpatient rehabilitation unit of a government medical center. PATIENTS: Twenty right-handed patients who showed left unilateral neglect on screening measures (Rey-Osterrieth Complex Figure, Random Letter Cancellation Test) were assigned to a CAT treatment group; and 20 patients who showed similar levels of unilateral neglect on the screening measures were assigned to a control group. INTERVENTIONS: All subjects were inpatients in an acute rehabilitation unit and received rehabilitation therapy, including physical and occupational therapy. The treatment group received the experimental, CAT program, 12 to 20 sessions of about 45 minutes each. Treatment consisted of 5 modules, each of increasing complexity, to improve attention to stimuli in the left hemisphere, and 2 simulated wheelchair obstacle courses to propel a wheelchair while avoiding obstacles. MAIN OUTCOME MEASURES: Computer tasks designed for this study (Video Tracking Test, Video Obstacle Course Test), a real-life wheelchair obstacle course (WCOC), and incident reports indicating falls and accidents. RESULTS: Trained subjects performed significantly better on the WCOC than control subjects (F(1,36) = 23.41, p = .00003). Also, trained subjects had fewer incident reports than control subjects during their hospitalization (chi(2)(1,)(n)(=38) = 5.15, p = .023). CONCLUSIONS: CAT can reduce unilateral neglect symptoms on experimental tasks and some measures of accident risk.

Physiological responses during hypoglycaemia induced by regular human insulin or a novel human analogue, insulin glargine.

AIM: Glargine, a product of recombinant technology, has different structural and physicochemical properties compared with native human insulin. We determined whether such differences are associated with alterations in the responses to hypoglycaemia induced by glargine. METHODS: Nineteen adults (six healthy and 13 with type 1 diabetes) underwent a 5-h hyperinsulinaemic (2 mU/kg/min(-1)) stepped hypoglycaemic clamps (hourly targets of 4.7, 4.2, 3.6, 3.1 and 2.5 mmol/l, respectively) on two occasions using intravenous infusion of regular human insulin or glargine, in random sequence. Hypoglycaemic symptoms, counter-regulatory hormones and glucose disposal rates were assessed at intervals throughout the clamps. A 1-week 'wash out' period was observed between studies. RESULTS: The peak total symptoms scores (mean +/- s.e.m.) at nadir blood glucose (2.5 mmol/1) were 18.83 +/- 2.68 (healthy) and 17.46 +/- 3.62 (diabetic) during regular insulin, and 18.50 +/- 3.20 (healthy) and 19.08 +/- 3.83 (diabetic) during glargine infusion. The peak epinephrine levels during hypoglycaemia were 767.8 +/- 140.4 pg/ml (regular insulin) and 608.8 +/- 129.9 pg/ml (glargine) among healthy subjects, and 332.5 +/- 54.8 pg/ml (regular insulin) and 321.8 +/- 67.4 pg/ml (glargine) in diabetic patients. Diabetic patients had blunted glucagon responses during hypoglycaemia with either insulin. Both insulins also elicited similar rates of glucose disposal. CONCLUSIONS: We conclude that insulin glargine and regular human insulin elicit comparable symptomatic and counter-regulatory hormonal responses during hypoglycaemia in healthy or diabetic subjects, and induce similar rates of glucose disposal. Since glargine is designed for subcutaneous (s.c.) use, it is possible (though unlikely) that our findings obtained using an intravenous protocol could differ from responses to hypoglycaemia induced by the s.c. route.

An analysis of the value of some antigen-antibody interactions used as diagnostic indicators in a treponemal Western blot (TWB) test for syphilis.

Densiometric quantitation and spreadsheet normalization were used to refine the parameters defining a treponemal Western blot (TWB) test for syphilis. Initially using 84 defined reactive and 105 defined non-reactive sera, we determined that the immune response to the 17 kDa antigen was the most critical of the following three candidate test determinants: the 47 kDa, 17 kDa and 15.5 kDa bands. In a second study using 124 cases of clinically diagnosed syphilis and 354 "normal" donors, a diluted serum sample was included as a minimal reactive control for the 17-kDa immune response. Reactivity to all three test determinants was obligatory for a test result to be interpreted as positive. Of the 124 cases of syphilis, 7 were nonreactive by TWB (sensitivity = 94%); of the 354 normal donors, 7 tested reactive (specificity = 98%). Forty (11%) normal serum samples had detectable but less than minimal reactivity to the 17 kDa band. Frequencies of immune response to a larger group of 12 antigens were tallied for the 124 clinically diagnosed cases of syphilis and an equal subset (124) of the normal group. In the normal subset, 72% and 52% of the samples had detectable reactivity to the 47 and 15.5 kDa antigens, respectively, while 10%, 5% and 3% reacted with the 17, 24 and 44.5 kDa antigens, respectively. Follow-up TWB testing of the clinically diagnosed cases revealed that previously untreated patients with primary or secondary syphilis were more likely to a show decrease in TWB reactivity than patients with latent symptoms who had been treated previously. As a diagnostic indicator of syphilis, the 17-kDa antigen was found to have the best combined attributes of sensitivity and specificity. Although, the highly specific 44.5 kDal and 24 kDal bands were often redundant as diagnostic indicators they are useful for the interpretation of borderline results. In addition, absence of the highly sensitive 47 and 15.5 kDa indicators should be useful in resolving some problem diagnoses.

Intravenous dolasetron for the prevention of postoperative nausea and vomiting after outpatient laparoscopic gynecologic surgery.

The newer 5-hydroxytryptamine type 3 (5-HT3) antagonists are sometimes considered for routine prophylaxis of postoperative nausea and vomiting (PONV) in high-risk patients. This multicenter, randomized, double-blind, placebo-controlled study compared the efficacy and safety of three single intravenous (IV) doses of dolasetron mesylate salt (12.5, 25, or 50 mg) for the prevention of PONV in 635 females undergoing outpatient laparoscopic gynecologic surgery. Antiemetic efficacy was evaluated over a 24-h postoperative period by recording the number and timing of emetic episodes; effects on nausea were evaluated by a visual analog scale (VAS). The proportion of complete responders (no emetic episodes and no escape medication in 24 h) was significantly higher with each dolasetron mesylate dose (> 50% for each dose; P < or = 0.0003) than with placebo (30.6%). Fewer patients given dolasetron required or requested escape antiemetic medication compared with placebo (P < 0.0003). Dolasetron-treated patients had significantly (P < 0.0357) lower median postdose maximum nausea VAS scores compared with placebo-treated patients. Patient satisfaction with dolasetron was high and, overall, was significantly (P = 0.0131) greater than that with placebo. Dolasetron was an effective and well tolerated preventive treatment for PONV resulting from laparoscopic gynecologic surgery.

Ranitidine versus cimetidine in the healing of erosive esophagitis.

Ranitidine 150 mg twice daily (BID) is an approved therapeutic approach for relieving the symptoms of gastroesophageal reflux disease. Ranitidine 150 mg four times daily (QID) and cimetidine 800 mg BID are indicated for endoscopically diagnosed erosive esophagitis. This 12-week, randomized, multicenter trial involving 696 patients compared ranitidine 150 mg BID and ranitidine 150 mg QID with cimetidine 800 mg BID in healing erosive esophagitis. Healing rates, as determined by endoscopy, at 4, 8, and 12 weeks were comparable with ranitidine 150 mg BID (38%, 56%, and 71%, respectively) and cimetidine 800 mg BID (37%, 52%, and 68%, respectively), as were reductions in heartburn frequency and antacid consumption. However, ranitidine 150 mg QID produced significantly higher healing rates (49%, 67%, and 77%, respectively) and greater reductions in heartburn frequency and antacid consumption than cimetidine 800 mg BID. All treatment regimens were well tolerated. Thus ranitidine 150 mg BID is as effective as cimetidine 800 mg BID, and ranitidine 150 mg QID is more effective than cimetidine 800 mg BID in healing erosive esophagitis and reducing heartburn frequency and antacid consumption.

Single-blind study of the effects of intravenous dolasetron mesylate versus ondansetron on electrocardiographic parameters in normal volunteers.

A single-blind, randomized, five-way cross-over, safety and tolerability trial was conducted to determine whether intravenous (i.v.) dolasetron mesylate at varying single doses induces changes in ECG intervals in healthy volunteers and to compare these changes with a single intravenous dose of ondansetron or placebo. Thirty healthy male volunteers received 1.2, 1.8, and 2.4 mg/kg i.v. dolasetron mesylate, 32 mg i.v. ondansetron, and placebo on 5 separate days. ECGs were recorded at intervals during the 24 h after study drug administration. The changes in ECG intervals observed after dolasetron mesylate or ondansetron were acute, transient, and asymptomatic. Dolasetron mesylate resulted in slight but statistically significant dose-related increases in heart rate (HR) and PR and QRS intervals (between h 0 and 4). A statistically significant increase in QTc interval was detected with both dolasetron mesylate (2.4 mg/kg) and ondansetron. Ondansetron also produced a slight but statistically significant increase in JT interval and a decrease in HR. These changes in ECG intervals were usually observed between h 0 and 4; all parameters returned to baseline within 8 h of treatment. The results demonstrate that both dolasetron mesylate and ondansetron prolong the QTc interval. However, dolasetron mesylate predominantly altered ECG parameters indicative of ventricular depolarization (QRS duration), whereas ondansetron predominantly affected ventricular repolarization as measured by a prolongation in the JT interval. Both dolasetron and ondansetron were well tolerated. The adverse event (AE) rate was 13.3% (4 of 30); all AE were of mild or moderate severity and were distributed across all dose arms.

Ranitidine 300 mg twice daily and 150 mg four-times daily are effective in healing erosive oesophagitis.

BACKGROUND: Ranitidine 150 mg q.d.s. is the currently recommended dosage in the United States for the treatment of erosive oesophagitis. To determine whether a higher dose of ranitidine administered less frequently would also be effective in healing erosive oesophagitis, we compared ranitidine 300 mg b.d. with ranitidine 150 mg q.d.s. in the treatment of erosive oesophagitis. METHODS: This multicentre, double-blind, randomized, placebo-controlled study conducted in the United States compared two dosages of ranitidine in 772 patients with endoscopically diagnosed erosive oesophagitis. Patients were treated with ranitidine 300 mg b.d., ranitidine 150 mg q.d.s. or placebo for up to 12 weeks. Endoscopies were repeated after 4, 8 and 12 weeks of treatment. RESULTS: Ranitidine 300 mg b.d. was significantly more effective than placebo in healing erosive oesophagitis at weeks 8 and 12 (51 vs. 36% and 66 vs. 52%, respectively; P < or = 0.004). Significantly higher healing rates were also achieved with ranitidine 150 mg q.d.s. compared with placebo at 4, 8 and 12 weeks (37 vs. 21%, 62 vs. 36% and 77 vs. 52%, respectively; P < 0.001). Healing rates were significantly higher with ranitidine 150 mg q.d.s. than with ranitidine 300 mg b.d. at all scheduled endoscopies (P < or = 0.041). CONCLUSIONS: Ranitidine 300 mg b.d. is effective in healing erosive oesophagitis and may be appropriate as an alternative dosage regimen to ranitidine 150 mg q.d.s. in some patients with erosive oesophagitis.