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Vs Placebo (v + placebo)
Selected AbstractsBudesonide delivered by dosimetric jet nebulization to preterm very low birthweight infants at high risk for development of chronic lung diseaseACTA PAEDIATRICA, Issue 12 2000B Jónsson We investigated the effect of an aerosolized corticosteroid (budesonide) on the oxygen requirement of infants at high risk for developing chronic lung disease (CLD) in a randomized, double-blind study. The study objective was to attain a 30% decrease in FiO2 levels in the budesonide treatment group after 14 d of therapy. Thirty very low birthweight (VLBW) infants (median (range)) gestational age 26 wk (23,29) and birthweight 805 g (525,1227) were randomized. Inclusion criteria were mechanical ventilation on day 6 of life, or if extubated on nasal continuous positive airway pressure with FiO2± 0.3. The budesonide (PulmicortÔ dose was 500 ,g bid, or placebo. The aerosol was delivered with a dosimetric jet nebulizer, with variable inspiratory time and breath sensitivity. Inhalations were started on day 7 of life. Twenty-seven patients completed the study. A significant lowering of the FiO2 levels at 21 d of life was not detected. Infants who received budesonide were more often extubated during the study period (7/8 vs 2/9) and had a greater relative change from baseline in their oxygenation index (budesonide decreased 26% vs placebo increased 60%). Subsequent use of intravenous dexamethasone or inhaled budesonide in the treatment group was significantly less. All patients required O2 supplementation on day 28 of life. At 36 wk postconceptual age, 61% of infants in the budesonide group needed supplemental O2 as opposed to 79% in the placebo group. No side effects on growth or adrenal function were observed Conclusion: We conclude that inhaled budesonide aerosol via dosimetric jet nebulizer started on day 7 of life for infants at high risk for developing CLD decreases the need for mechanical ventilation similar to intravenous dexamethasone, but without significant side effects. [source] Efficacy and safety of on-demand tadalafil for the treatment of erectile dysfunction in South-East Asian menINTERNATIONAL JOURNAL OF UROLOGY, Issue 6 2006YING LU GUO Aim:, Tadalafil is an inhibitor of phosphodiesterase type 5 used for the treatment of erectile dysfunction (ED). The efficacy and safety of tadalafil have been evaluated extensively in Western populations. Our aim was to assess the efficacy and safety of on-demand tadalafil for the treatment of ED in South-East Asian men. Methods:, This was a randomized, double-blind, placebo-controlled study of men with mild to severe ED of various etiologies randomized to receive placebo (n = 122), tadalafil 10 mg (n = 120), or tadalafil 20 mg (n = 125), taken as needed (maximum once daily) for 12 weeks. Efficacy assessments included the International Index of Erectile Function (IIEF), the Sexual Encounter Profile (SEP) diary, and a Global Assessment Question (GAQ). Results:, Men from China, Singapore, and the Philippines participated in this trial (n = 367). Compared with placebo, tadalafil significantly improved erectile dysfunction on all efficacy outcomes (P < 0.001). Patients receiving tadalafil 10 mg and 20 mg experienced a significant mean improvement of 8.1 and 8.7, respectively, in the IIEF Erectile Function (IIEF-EF) domain score from baseline (vs placebo 2.4, P < 0.001). In patients receiving tadalafil 10 mg and 20 mg, the mean per-patient success rate for intercourse attempts (SEP3) was 62% and 70%, respectively, compared with 32% for the placebo group (P < 0.001). Of patients who received tadalafil 10 mg and 20 mg, 81% and 86% reported improved erections at endpoint (GAQ) compared with 44% in the placebo group (P < 0.001). The most common adverse events reported by patients were headache, back pain, dyspepsia, and dizziness. Conclusions:, Tadalafil was an effective and well-tolerated treatment for South-East Asian men with ED. [source] Maintenance Treatment for Old-Age Depression Preserves Health-Related Quality of Life: A Randomized, Controlled Trial of Paroxetine and Interpersonal PsychotherapyJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 9 2007Alexandre Y. Dombrovski MD OBJECTIVES: To determine whether maintenance antidepressant pharmacotherapy and interpersonal psychotherapy sustain gains in health-related quality of life (HR-QOL) achieved during short-term treatment in older patients with depression. DESIGN: After open combined treatment with paroxetine and interpersonal psychotherapy, responders were randomly assigned to a two (paroxetine vs placebo) by two (monthly interpersonal psychotherapy vs clinical management) double-blind, placebo-controlled maintenance trial. HR-QOL outcomes were assessed over 1 year. SETTING: University-based clinic. PATIENTS: Of the referred sample of 363 persons aged 70 and older with major depression, 210 gave consent, and 195 started acute treatment; 116 met criteria for recovery, entered maintenance treatment, and were included in this analysis. INTERVENTIONS: Paroxetine; monthly manual-based interpersonal psychotherapy. MEASUREMENTS: Overall HR-QOL as measured using the Quality of Well-Being Scale (QWB) and six specific HR-QOL domains derived from the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) subscales. RESULTS: All domains of HR-QOL except physical functioning improved with successful acute and continuation treatment. After controlling for any effects of psychotherapy, pharmacotherapy was superior to placebo in preserving overall well-being (P=.04, effect size (r)=0.23), social functioning (P=.02, r=0.27), and role limitations due to emotional problems (P=.007, r=0.30). Interpersonal psychotherapy (controlling for the effects of pharmacotherapy) did not preserve HR-QOL better than supportive clinical management. CONCLUSION: Maintenance antidepressant pharmacotherapy is superior to placebo in preserving improvements in overall well-being achieved with treatment response in late-life depression. No such benefit was seen with interpersonal psychotherapy. [source] Efficacy and Safety of Rofecoxib 12.5 mg Versus Nabumetone 1,000 mg in Patients with Osteoarthritis of the Knee: A Randomized Controlled TrialJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 5 2004Alan J. Kivitz MD Objectives: To evaluate the use of starting doses of rofecoxib and nabumetone in patients with osteoarthritis (OA) of the knee. Design: A 6-week, randomized, parallel-group, double-blind, placebo-controlled study. Setting: One hundred thirteen outpatient sites in the United States. Participants: A total of 1,042 male and female patients aged 40 and older with OA of the knee (>6 months). Interventions: Rofecoxib 12.5 mg once a day (n=424), nabumetone 1,000 mg once a day (n=410), or placebo (n=208) for 6 weeks. Measurements: The primary efficacy endpoint was patient global assessment of response to therapy (PGART) over 6 weeks, which was also specifically evaluated over the first 6 days. The main safety measure was adverse events during the 6 weeks of treatment. Results: The percentage of patients with a good or excellent response to therapy as assessed using PGART at Week 6 was significantly higher with rofecoxib (55.4%) than nabumetone (47.5%; P=.018) or placebo (26.7%; P<.001 vs rofecoxib or nabumetone). Median time to first report of a good or excellent PGART response was significantly shorter in patients treated with rofecoxib (2 days) than with nabumetone (4 days, P=.002) and placebo (>5 days, P<.001) (nabumetone vs placebo; P=.007). The safety profiles of rofecoxib and nabumetone were generally similar, including gastrointestinal, hypertensive, and renal adverse events. Conclusion: Rofecoxib 12.5 mg daily demonstrated better efficacy over 6 weeks of treatment and quicker onset of OA efficacy over the first 6 days than nabumetone 1,000 mg daily. Both therapies were generally well tolerated. [source] Efficacy of grass pollen sublingual immunotherapy for three consecutive seasons and after cessation of treatment: the ECRIT studyALLERGY, Issue 9 2009H. Ott Background:, Data supporting a carry-over effect with sublingual immunotherapy (SLIT) are scarce. This randomized, double-blind, placebo-controlled study evaluated the efficacy, carry-over effect and safety of grass pollen SLIT using co-seasonal treatment. Methods:, Patients (7.9,64.7 years) with grass pollen allergy received ultra-rush titration with increasing doses (30, 90, 150 and 300 IR) of a 5-grass pollen mixture every 20 min at the start of the pollen seasons, followed by 300 IR daily until the end of the pollen seasons. A baseline season (no SLIT) was followed by three consecutive treatment seasons and one follow-up season. Symptoms, medication and adverse events were documented and specific immunoglobulin (Ig)E and IgG4 measured. Results:, Data were analysed for 183 of the 213 randomized patients. Mean treatment duration varied between seasons (81.8,92.7 days). Combined scores (symptoms and medication) improved progressively across treatment seasons (up to 44.7% improvement for SLIT compared with baseline) and fluctuated between ,11.3% and ,14.8% for placebo (P < 0.05). Similar changes were observed for symptom scores, with a successive decrease of 39.7% (SLIT) and fluctuations between +13.6% and ,1.51% for placebo (P < 0.05). Combined score (P = 0.0508) and symptom score improvements (P = 0.0144) with SLIT continued during follow up. Increases in specific IgG4 observed in the first season were sustained for SLIT vs placebo throughout treatment (P = 0.0001). Titration and daily SLIT were well tolerated. No serious systemic or anaphylactic reactions were reported. Conclusions:, Seasonal SLIT with ultra-rush titration is well tolerated and effective from the first treatment season onwards. These data indicate a carry-over effect of seasonal SLIT. [source] Comparison of the efficacy and safety of bilastine 20 mg vs desloratadine 5 mg in seasonal allergic rhinitis patientsALLERGY, Issue 1 2009C. Bachert Background:, Bilastine is a novel, nonsedating H1 -antihistamine developed for symptomatic treatment of Allergic Rhinitis and Chronic Idiopathic Urticaria. The objective of this study was to compare the efficacy and safety of bilastine 20 mg vs placebo and desloratadine 5 mg in subjects with seasonal allergic rhinitis (SAR). Methods:, This randomized, double blind, placebo-controlled, parallel-group multicentre study evaluated the effect of 2 weeks' treatment with bilastine 20 mg, desloratadine 5 mg or matched placebo once daily, in 12,70 years old symptomatic SAR patients. All subjects assessed the severity of nasal (obstruction, rhinorrhoea, itching, and sneezing) and nonnasal (ocular itching, tearing, ocular redness, itching of ears and/or palate) symptoms on a predetermined scale to provide a total symptom score (TSS), composed of nasal and nonnasal symptom scores (NSS and NNSS, respectively). The primary efficacy measure was the area under the curve (AUC) for the TSS over the entire treatment period. Results:, Bilastine 20 mg significantly reduced the AUC of TSS to a greater degree from baseline compared to placebo (98.4 with bilastine vs 118.4 with placebo; P < 0.001), but not compared to desloratadine 5 mg (100.5). Bilastine 20 mg was not different from desloratadine 5 mg but significantly more effective than placebo in improving the NSS, NNSS, and rhinitis-associated discomfort scores (P < 0.05), and rhinoconjunctivitis quality of life questionnaire total (P < 0.005) and four out of seven individual domain (P < 0.05) scores. The incidence of treatment emergent adverse events was similar for bilastine (20.6%), desloratadine (19.8%), and placebo (18.8%). Conclusion:, Bilastine 20 mg once daily was efficacious, safe and not different from desloratadine 5 mg once daily in the treatment of SAR symptoms. [source] Efficacy of grass pollen sublingual immunotherapy for three consecutive seasons and after cessation of treatment: the ECRIT studyALLERGY, Issue 1 2009H. Ott Background:, Data supporting a carry-over effect with sublingual immunotherapy (SLIT) are scarce. This randomized, double-blind, placebo-controlled study evaluated the efficacy, carry-over effect and safety of grass pollen SLIT using co-seasonal treatment. Methods:, Patients (7.9,64.7 years) with grass pollen allergy received ultra-rush titration with increasing doses (30, 90, 150 and 300 IR) of a 5-grass pollen mixture every 20 min at the start of the pollen seasons, followed by 300 IR daily until the end of the pollen seasons. A baseline season (no SLIT) was followed by three consecutive treatment seasons and one follow-up season. Symptoms, medication and adverse events were documented and specific immunoglobulin (Ig)E and IgG4 measured. Results:, Data were analysed for 183 of the 213 randomized patients. Mean treatment duration varied between seasons (81.8,92.7 days). Combined scores (symptoms and medication) improved progressively across treatment seasons (up to 44.7% improvement for SLIT compared with baseline) and fluctuated between ,11.3% and ,14.8% for placebo (P < 0.05). Similar changes were observed for symptom scores, with a successive decrease of 39.7% (SLIT) and fluctuations between +13.6% and ,1.51% for placebo (P < 0.05). Combined score (P = 0.0508) and symptom score improvements (P = 0.0144) with SLIT continued during follow up. Increases in specific IgG4 observed in the first season were sustained for SLIT vs placebo throughout treatment (P = 0.0001). Titration and daily SLIT were well tolerated. No serious systemic or anaphylactic reactions were reported. Conclusions:, Seasonal SLIT with ultra-rush titration is well tolerated and effective from the first treatment season onwards. These data indicate a carry-over effect of seasonal SLIT. [source] Randomized double-blind controlled study with sublingual carbamylated allergoid immunotherapy in mild rhinitis due to mitesALLERGY, Issue 7 2006G. Passalacqua Background:, The clinical efficacy of sublingual immunotherapy (SLIT) in mite allergy and in mild disease is still a matter of debate, thus we performed a long-term clinical trial. Methods:, The study was randomized, double-blind and placebo-controlled. After a 1-year assessment, 68 patients with mild rhinitis with/without asthma due to mites were randomized to drugs + placebo or drugs + SLIT for 2 years. Sublingual immunotherapy was given as soluble tablets of monomeric carbamylated allergoid. Clinical scores for asthma and rhinitis (0, absent to 3, severe) and drug consumption were assessed by diary card in the period November,February. Quality of life was assessed before and after each observation period and pharmaco-economy data were evaluated as well. Results:, Fifty-six patients completed the study. The rate of dropouts was similar in the two groups. No relevant side effect was reported. There was a significant reduction of total clinical scores (P < 0.05) in the active group vs placebo at the first year, but not at the second whereas nasal obstruction significantly improved in both years (P < 0.05). The reduction of drug intake score was significant only at the first year. No change was observed concerning most of the Short Form-36 items, because at baseline all patients displayed a normal profile. A significant change in SLIT group was seen for the item ,change in health status'. The need for extra visits was significantly lower in the active group (25%vs 43%). Conclusions:, Sublingual immunotherapy was clinically effective and safe in mite-induced mild disease. [source] Risks and side-effects of intrathecal morphine combined with spinal anaesthesia: a meta-analysisANAESTHESIA, Issue 6 2009M. Gehling Summary Intrathecal morphine is often used for postoperative analgesia after surgery. We performed a meta-analysis to obtain more detailed information on the frequency of side-effects in patients receiving intrathecal morphine in combination with spinal anaesthesia compared with placebo treated patients. We clustered the analysis to patients receiving placebo, less than morphine 0.3 mg (M < 0.3), or equal to or more than morphine 0.3 mg (M , 0.3) and calculated the risk ratios of morphine vs placebo. Twenty-eight studies investigating 46 morphine groups vs placebo were included. A total of 790 patients with intrathecal morphine and 524 patients who received placebo were analysed. Compared with placebo the lower dose of morphine resulted in an increase of nausea (RR 1.4, 95% CI 1.1,1.7), vomiting (RR 3.1, 95% CI 1.5,6.4) and pruritus (RR 1.8, 95% CI 1.4,2.2). The higher dose resulted in an increased risk ratio for pruritus (RR 5.0, 95% CI 2.9,8.6), but not nausea (RR 1.2, 95% CI 0.9,1.6) or vomiting (RR 1.3, 95% CI 0.9,1.9). Overall, intrathecal morphine did not increase respiratory depression. However, the higher dose of intrathecal morphine was associated with more episodes of respiratory depression (7/80) compared with the lower dose (2/247). Intrathecal morphine is associated with a mild increase in side-effects. With a dose < 0.3 mg we found there were no more episodes of respiratory depression than in placebo patients who received systemic opioid analgesia. [source] Ondansetron has similar clinical efficacy against both nausea and vomitingANAESTHESIA, Issue 2 2009R. M. Jokela Summary Ondansetron is widely believed to prevent postoperative vomiting more effectively than nausea. We analysed data from 5161 patients undergoing general anaesthesia who were randomly stratified to receive a combination of six interventions, one of which was 4 mg ondansetron vs placebo. For the purpose of this study a 20% difference in the relative risks for the two outcomes was considered clinically relevant. Nausea was reduced from 38% (969/2585) in the control to 28% (715/2576) in the ondansetron group, corresponding to a relative risk of 0.74, or a relative risk reduction of 26%. Vomiting was reduced from 17% (441/2585) to 11% (293/2576), corresponding to a relative risk of 0.67, or a relative risk reduction of 33%. The relative risks of 0.67 and 0.74 were clinically similar and the difference between them did not reach statistical significance. We thus conclude that ondansetron prevents postoperative nausea and postoperative vomiting equally well. [source] Coenzyme Q10 improves contractility of dysfunctional myocardium in chronic heart failureBIOFACTORS, Issue 1-4 2005Romualdo Belardinelli Abstract Background: There is evidence that plasma CoQ10 levels decrease in patients with advanced chronic heart failure (CHF). Objective: To investigate whether oral CoQ10 supplementation could improve cardiocirculatory efficiency in patients with CHF. Methods: We studied 21 patients in NYHA class II and III (18M, 3W, mean age 59 ±9 years) with stable CHF secondary to ischemic heart disease (ejection fraction 37 ± 7%), using a double-blind, placebo-controlled cross-over design. Patients were assigned to oral CoQ10 (100 mg tid) and to placebo for 4 weeks, respectively. Results: CoQ10 supplementation resulted in a threefold increase in plasma CoQ10 level (P<0.0001 vs placebo). Systolic wall thickening score index (SWTI) was improved both at rest and peak dobutamine stress echo after CoQ10 supplementation (+12.1 and 15.6%, respectively, P<0.05 vs placebo). Left ventricular ejection fraction improved significantly also at peak dobutamine (15% from study entry P<0.0001) in relation to a decrease in LV end-systolic volume index (from 57 ± 7 mL/m2 to 45 mL/m2, P<0.001). Improvement in the contractile response was more evident among initially akinetic (+33%) and hypokinetic (+25%) segments than dyskinetic ones (+6%). Improvement in SWTI was correlated with changes in plasma CoQ10 levels (r=,0.52, P<0.005). Peak VO2 was also improved after CoQ10 as compared with placebo (+13%, <0.005). No side effects were reported with CoQ10. Conclusions: Oral CoQ10 improves LV contractility in CHF without any side effects. This improvement is associated with an enhanced functional capacity. [source] Comparison of fesoterodine and tolterodine extended release for the treatment of overactive bladder: a head-to-head placebo-controlled trialBJU INTERNATIONAL, Issue 1 2010Sender Herschorn Study Type , Therapy (RCT) Level of Evidence 1b OBJECTIVE To compare the efficacy and tolerability of fesoterodine 8 mg with tolterodine extended-release (ER) 4 mg and placebo in a randomized clinical trial of patients with an overactive bladder (OAB). PATIENTS AND METHODS In this 12-week double-blind, double-dummy, placebo-controlled, randomized clinical trial, eligible patients reported OAB symptoms for ,3 months and recorded ,8 voids and ,1 urgency urinary incontinence (UUI) episode per 24 h in 3-day bladder diaries at baseline. Patients were randomized in a 2:2:1 ratio to fesoterodine (4 mg for 1 week then 8 mg for 11 weeks); tolterodine ER 4 mg; or placebo (with sham dose escalation for tolterodine ER and placebo). Endpoints were changes from baseline to week 12 in UUI episodes (primary endpoint), total and nocturnal voids, urgency episodes, severe urgency episodes, and frequency-urgency sum per 24 h; mean voided volume per void (MVV); and the OAB questionnaire (OAB-q), Patient Perception of Bladder Condition (PPBC), and Urgency Perception Scale (UPS). Safety and tolerability were assessed and summarized over the 12-week study period. RESULTS Fesoterodine (636 patients) significantly improved UUI episodes at week 12 (primary endpoint) compared with tolterodine ER (641 patients; P = 0.017) and placebo (313 patients; P < 0.001). Fesoterodine also produced significantly greater improvements than tolterodine ER in MVV (P = 0.005). Fesoterodine significantly improved all diary endpoints compared with placebo (P < 0.001), except for nocturnal voids (P = 0.327). Tolterodine ER significantly improved all diary endpoints vs placebo (P < 0.001), except for nocturnal voids (P = 0.506) and MVV (P = 0.103). Diary dry rates (the proportion of patients reporting no UUI episodes at endpoint among those with one or more UUI episodes at baseline) were significantly higher with fesoterodine (64%) than with tolterodine ER (57%; P = 0.015) and placebo (45%; P < 0.001). Improvements in PPBC, UPS and OAB-q scale and domain scores at week 12 were all significantly better with fesoterodine than placebo (all P < 0.001) and tolterodine ER (all P < 0.05) except for the OAB-q Sleep domain vs tolterodine ER (P = 0.081). Dry mouth and constipation rates were 28% and 5% in the fesoterodine group, 16% and 4% in the tolterodine ER group, and 6% and 3% with placebo, respectively. Discontinuations due to treatment-emergent adverse events were 6%, 4% and 2% in the fesoterodine, tolterodine ER, and placebo groups, respectively. CONCLUSION In patients with OAB, fesoterodine 8 mg showed superior efficacy over tolterodine ER 4 mg and placebo in reducing UUI episodes (primary endpoint) and in improving most patient-reported outcome measures. Both active treatments were well tolerated. [source] Doxazosin for treating lower urinary tract symptoms compatible with benign prostatic obstruction: a systematic review of efficacy and adverse effectsBJU INTERNATIONAL, Issue 9 2004Roderick MacDonald The first paper in this section is a systematic review of the efficacy and adverse effects of doxazosin for treating LUTS compatible with benign prostatic obstruction. The criteria for inclusion were met by 13 studies involving 6033 men. The authors found evidence that doxazosin was effective and well tolerated in patients with LUTS. Combined therapy was superior to doxazosin alone in reducing the risk of clinical progression and other long-term complications of this condition. Authors from the UK reviewed the long-term results they achieved with an endourethral stent for treating BPH; quite a large proportion of patients had either died from unrelated causes or had had the stent removed. They stressed the necessity for careful case selection, but showed that it was a safe treatment for BPH in poor-risk patients. OBJECTIVE To evaluate the efficacy and adverse effects of doxazosin for treating lower urinary tract symptoms (LUTS) compatible with benign prostatic obstruction (BPO). METHODS Randomized controlled trials were included in the meta-analysis if: the study duration was ,,1 month; the study involved men with symptomatic BPO; and doxazosin was compared with placebo or active controls. Study and patient characteristics and outcome data were extracted in duplicate onto standardized forms using a prospectively developed protocol. RESULTS Thirteen studies involving 6033 men with (mean age 64 years) met the inclusion criteria; 10 were placebo-controlled, including two with combined doxazosin/finasteride therapy and finasteride monotherapy arms. Three trials were a comparison with other ,-blockers. The study duration was 1,54 months. The mean baseline symptom scores and peak urinary flow (PUF) rates were indicative of moderate BPO. Doxazosin gave significant improvements in LUTS, assessed by symptom scores, vs placebo and finasteride in the short- to long-term. Two long-term studies (1 and 4 years) reported mean changes from baseline for the International Prostate Symptom Score of ,,8.3 and ,,6.6 points (,49% and ,,39%) for doxazosin and ,,5.7 and ,,4.9 points (,33% and ,,29%) for placebo, respectively. Doxazosin significantly increased PUF rates vs placebo. In pooled results from three studies, the weighted mean difference in the mean change from baseline vs placebo was 1.6 mL/s (95% confidence interval 1.2,2.1). Efficacy was comparable with other ,1,blockers. In the long-term (>4 years) doxazosin was no better then finasteride in improving PUF. Combined doxazosin and finasteride significantly reduced the risk of overall clinical progression of BPO vs each drug separately in men followed for >4 years. Absolute risk reductions vs placebo were 11.3%, 6.9% and 6.4% for combined therapy, doxazosin and finasteride, respectively (P < 0.001). Improvements in symptom scores and PUF were also significantly greater with combined than monotherapy, and the former reduced the need for invasive treatment for BPO and the risk of long-term urinary retention, although the absolute reductions in risk vs placebo were small (<4%). Dizziness and fatigue were significantly more common with doxazosin than placebo (11% vs 7%, and 6% vs 3%, respectively). Adverse events reported for combined therapy were similar to those with each monotherapy. CONCLUSION The evidence indicates that doxazosin is effective and generally well tolerated for improving LUTS and PUF in men with symptomatic BPO. Combined therapy was better than doxazosin alone in reducing the risk of clinical progression of BPO and other long-term complications related to BPO. [source] Duloxetine vs placebo in the treatment of stress urinary incontinence: a four-continent randomized clinical trialBJU INTERNATIONAL, Issue 3 2004R.J. Millard OBJECTIVES To further assess, in a phase 3 study, treatment with duloxetine for women with stress urinary incontinence (SUI) in other geographical regions, including Argentina, Australia, Brazil, Finland, Poland, South Africa and Spain, as previous trials in North America and Europe provided evidence for the safety and efficacy of duloxetine as a pharmacological treatment for SUI in women. PATIENTS AND METHODS The study included 458 women aged 27,79 years enrolled in a double-blind, placebo-controlled trial. The patients with predominantly SUI were identified using a validated clinical algorithm. They were randomly assigned to receive placebo (231) or duloxetine 40 mg twice daily (227) for 12 weeks. The primary outcome variables included the incontinence episode frequency (IEF) and the Incontinence Quality of Life (I-QOL) questionnaire. Van Elteren's test was used to analyse the percentage changes in IEF where the stratification variable was weekly baseline IEF (IEF <14 and ,14). Analysis of covariance was used to analyse I-QOL scores. RESULTS The mean baseline IEF was 18.4/week; 55% of patients had a baseline IEF of ,,14. There was a significantly greater median decrease in IEF with duloxetine with placebo (54% vs 40%, P = 0.05), with comparable significant improvements in quality of life (I-QOL score increases of 10.3 vs 6.4, P = 0.007). The improvements with duloxetine were associated with significantly greater increases in voiding intervals than with placebo (20.4 vs 8.5 min, P < 0.001). The placebo response was 10.7% and 12.5% higher than those reported in two European and North American phase 3 trials. This may have been related to more patients being naïve for incontinence management in the current trial. Discontinuation rates for adverse events were 1.7% for placebo and 17.2% for duloxetine (P < 0.001), with nausea being the most common reason for discontinuation (3.1%); it was the most common adverse event with duloxetine, but was mild or moderate in most (81%), did not worsen in any patient and resolved within 7 days in 60% and within 1 month in 86% of continuing patients; 88% of women who experienced nausea while taking duloxetine completed the trial. CONCLUSIONS These results show improvements in incontinence and quality of life with duloxetine 40 mg twice daily for 12 weeks that are in keeping with those reported in two other recently completed phase 3 trials in Europe and North America. [source] Assessment of the effect of dextromethorphan and ketamine on the acute nociceptive threshold and wind-up of the second pain response in healthy male volunteersBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 6 2002A. M. Hughes Aims, The aim of this study was to assess the efficacy of dextromethorphan and ketamine relative to placebo on the acute nociceptive threshold and wind-up of second pain response in healthy male volunteers. Methods, The trial was a randomized, double-blind, placebo-controlled, three period crossover, double dummy design in 12 healthy male volunteers. During each of the three periods (which were separated by a 1 week washout period) each volunteer received either a single oral dose of 0.7 mg kg,1 dextromethorphan and placebo to ketamine, or placebo to dextromethorphan followed by a single intravenous injection of 0.375 mg kg,1 ketamine, or placebo to both dextromethorphan and ketamine. The trial did not schedule administration of both ketamine and dextromethorphan together. Acute nociceptive thresholds and wind-up of second pain were measured in the skin of the thenar eminence of the ventral surfaces of the right and left hands, using a SOMEDICTM thermotest apparatus, before and at the estimated tmax for dextromethorphan (i.e. 2.15 h). Blood pressure and heart rate were also monitored before dosing and after the dosing regimen. Results, Neither dextromethorphan nor ketamine had any significant effect on acute nociceptive thresholds on either hand (P>0.05). Moreover, dextromethorphan was without any significant effect (P>0.05) on the wind-up of the second pain response on either hand. The lsmean number of stimuli tolerated vs placebo (95% confidence intervals of the difference in number of stimuli in parentheses) were 15.84 vs 16.48 (,5.52, 4.24) and 11.75 vs 15.25 (,11.89, 4.90) for left- and right-hand, respectively, following dextromethorphan administration. In contrast ketamine produced significant reductions in wind-up to second pain in both the left and right hands (P=0.0002 and 0.0386, respectively). The lsmean numbers of stimuli tolerated vs placebo (95% confidence intervals of the difference in number of stimuli in parentheses) were 28.41 vs 16.48 (6.60, 17.25) and 25.00 vs 15.25 (0.58, 18.93) for left- and right-hand, respectively. Conclusions, Wind-up of second pain induced by noxious heat is sensitive to intervention by ketamine, which is known to block the NMDA receptor. These data infer that the wind-up phenomenon evoked by noxious heat involves the activation of NMDA receptors. This volunteer model of pain may have utility in the evaluation of agents that modulate their antinociceptive actions via NMDA mechanisms. [source] A double masked placebo controlled study on the effect of nifedipine on optic nerve blood flow and visual field function in patients with open angle glaucomaBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 2 2001Georg Rainer Aims, To investigate whether nifedipine affects ocular perfusion or visual fields in open angle glaucoma patients. Methods, In a parallel group study nifedipine or placebo was administered for 3 months (n = 30). Ocular fundus pulsation amplitude (FPA), cup blood flow (Flowcup) and visual field mean deviation (MD) were measured. Results, Five patients receiving nifedipine discontinued due to adverse events. Nifedipine did not affect FPA [difference: 0.3 µm (95% CI ,0.3,0.9); P = 0.70], Flowcup: [difference: ,9 rel.units (95% CI ,133,114); P = 0.99], or MD [difference: 0.2dB (95% CI ,2.2,2.7); P = 0.51]vs placebo. Conclusions, Systemic nifedipine is not well tolerated in glaucoma patients and exerts no effect on visual fields or ocular perfusion. [source] A pooled analysis of adjunctive topiramate in refractory partial epilepsyACTA NEUROLOGICA SCANDINAVICA, Issue 1 2003K. Peeters Objectives , To evaluate the impact of different dosages of topiramate (TPM) add-on to stable antiepileptic therapy for refractory partial epilepsy in adults. Material and methods , Pooled intention-to-treat analysis of six similarly designed double-blind, placebo-controlled trials, including 481 patients treated with doses of TPM 200, 400, 600 and 800 mg/day, and 265 patients receiving placebo. Results , Seizures were reduced by ,50% from baseline in 41% of TPM-treated patients and 15% of placebo-treated patients (P < 0.001); 5 and 0.8%, respectively, were seizure-free (P < 0.003). TPM was significantly better than placebo regardless of gender, age, baseline seizure rate as well as number and type of concomitant antiepileptic drugs. Efficacy was statistically significant in favour of TPM at all dose levels: at least 50% seizure reduction was achieved in 40% of patients with 200 mg, 41% with 400 mg, 44% with 600 mg and 41% with 800 mg TPM when compared with 15% with placebo (P , 0.001 for each dosage arm vs placebo). The median reduction in monthly seizure frequency was 38%, 42%, 45% and 38% vs 8%, respectively (P , 0.001). Moreover, response to TPM was significantly superior to placebo at each of the dose levels tested for most of the baseline variables. The total percentage of withdrawals increased with the dosage, and the withdrawals caused by adverse events increased from 3% with placebo to 7% with 200 mg TPM (not significant vs placebo), 15% with 400 mg TPM (P = 0.08), 16% with 600 mg TPM (P = 0.002) and 15% with 800 mg TPM (P = 0.003). Conclusion , The efficacy of TPM add-on in partial epilepsy is consistent across efficacy endpoints and independent of study population characteristics. The response at 200 mg TPM is similar to the response at higher doses, but as drop-outs caused by adverse events are more frequent above the 200 mg dose, this pooled analysis supports that 200 mg daily is a good target dose for add-on therapy in most patients with partial epilepsy, showing an excellent balance between efficacy and tolerability. [source] Alpha-dihydroergocryptine in the treatment of de novo parkinsonian patients: results ofa multicentre, randomized, double-blind, placebo-controlled studyACTA NEUROLOGICA SCANDINAVICA, Issue 6 2000B. Bergamasco Introduction, A multicentre, randomized, double-blind, placebo-controlled, parallel group study was carried out in 123 patients suffering from never treated (de novo) idiopathic Parkinson's disease (PD). The aim of the study was to confirm the efficiency and safety of ,-dihydroergocryptine (,-DHEC) given as monotherapy in the symptomatic treatment of PD. The total score of the Unified Parkinson's Disease Rating Scale (UPDRS) was identified as the efficacy target variable. Patients and methods, Sixty-two patients (32 males, 30 females, mean age±SD 64±10) were randomized to ,-dihydroergocryptine and 61 (30 males, 31 females, mean age 63.8±9.1) to placebo. According to the experimental design, a 18-month double-blind phase vs placebo was followed. Two interim analyses were planned both at the 3rd and 12th month of treatment, in order to avoid continuation on placebo, if clear differences between groups were found (stopping criterium: nominal significance level equal to 0.022 in the analysis of the target variable). Analysis of variance was performed both on the per protocol (PP) and intent-to-treat (ITT) sample. Results, The results on the first interim analysis showed significant differences between treatment groups of the UPDRS total score both in the ITT (115 patients, ,-DHEC: No. 56; placebo: No. 59; P=0.019) and PP (96 patients, ,-DHEC: No. 46; placebo: No. 50; P=0.001) sample, why the trial was stopped. At the time of stopping the trial, 73 patients (,-DHEC: No. 37; placebo: No. 36) had reached the 6-month observation visit; the analysis carried out on this subset of patients confirmed the efficacy of ,-dihydroergocryptine in early PD and the correctness of the decision to stop. The incidence of adverse drug reactions (ADR) did not differ between ,-dihydroergocryptine and placebo recipients, gastrointestinal complaints being the most frequent. Conclusion, The results indicate that ,-dihydroergocryptine is safe and effective in improving symptoms of de novo parkinsonian patients. [source] Montelukast does not prevent reactive airway disease in young children hospitalized for RSV bronchiolitisACTA PAEDIATRICA, Issue 11 2009M Proesmans Abstract Aim:, To evaluate the long-term effect of montelukast on symptoms of cough and wheeze following RSV bronchiolitis. Methods:, Fifty eight patients (aged , 24 months) hospitalized with a first episode of RSV bronchiolitis were enrolled in this double blind prospective randomized trial comparing montelukast (n = 31) vs placebo (n = 27). Results:, During the 3-month treatment period, there were no statistical significant differences between the two groups for symptom-free days and nights (48.5 [interquartile range 33.0.0,66.0] for montelukast vs 57.0 [29.0,71.0] for placebo p = 0.415) nor disease-free days and nights (44.5 days [26.0,54.0] vs 53.0 [22.3,71.0]; p = 0.266). During the 1 year follow-up, there were 41 exacerbations in the montelukast group vs 54 exacerbations in the placebo group (p = 0.57). Time to first exacerbation was not different. Number of unscheduled visits and need to start inhaled steroids were comparable in the two groups. Conclusion:, Treatment with montelukast after hospital admission for RSV bronchiolitis in children younger than 2 years of age did not reduce symptoms of cough and wheeze. We cannot exclude that a subgroup of children may, however, benefit from this treatment. [source] Renin Inhibitors in Chronic Heart Failure: The Aliskiren Observation of Heart Failure Treatment Study in ContextCLINICAL CARDIOLOGY, Issue 9 2010FESC, FRACP, Henry Krum PhD Renin-angiotensin aldosterone system (RAAS) activation is a key neurohormonal contributor to the progression of chronic heart failure. Strategies that block this activation have consistently demonstrated major beneficial impacts on morbidity and mortality in this setting. Direct renin inhibitors (DRIs) present a novel opportunity to block at an additional or alternative step in this pathway, that being conversion of angiotensinogen to angiotensin I. Theoretical benefits of blocking at the level of renin include: inhibition of the reflex activation of plasma renin activity induced by conventional downstream RAAS blockers. Minimization of angiotensin II and/or aldosterone escape and blocking upstream at the rate-limiting step of angiotensin I production. Preclinical and early-phase clinical studies have largely supported this hypothesis. In the Aliskiren Observation of Heart Failure Treatment study, patients with systolic chronic heart failure receiving background angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers and ,-blockers benefited from aliskiren in reduction vs placebo of plasma levels of brain natriuretic peptide, the primary efficacy endpoint of that study. Large-scale outcome trials are, however, required to definitively determine the benefits of a DRI strategy additional to, or as an alternative to, conventional approaches such as ACE inhibitors in the systolic chronic heart failure setting. Copyright © 2010 Wiley Periodicals, Inc. The authors have no funding, financial relationships, or conflicts of interest to disclose. [source] Effects of magnesium sulphate on amplitude-integrated continuous EEG in asphyxiated term neonatesACTA PAEDIATRICA, Issue 10 2002F Groenendaal In this study it is hypothesized that magnesium sulphate in asphyxiated full-term neonates could lead to a gradual improvement in background pattern of the amplitude integrated EEG (aEEG), an early marker of hypoxic-ischaemic brain injury. In a double-blind, randomized, controlled pilot study of 22 asphyxiated full-term neonates 8 received magnesium sulphate, reaching serum Mg2+ levels of 2.5 mmol/L. Magnesium sulphate had no immediate effect on aEEG-patterns. At 12 h of age, aEEG was more depressed compared with aEEG at 3 h in 6 of the 8 magnesium-treated neonates, and in 3 of the 14 placebo-treated neonates (Mg2+ vs placebo: p < 0.05, Mann-Whitney). No further significant changes in aEEG were seen between 12 and 24 h. Outcome was unfavourable in 4 of the 8 magnesium-treated neonates, and in 8 of the 14 placebo-treated neonates. Conclusion: Magnesium sulphate did not have a positive effect on aEEG patterns in this small group of asphyxiated term neonates. [source] | ||||||||||