Morning versus evening dosing of desloratadine in seasonal allergic rhinitis: a randomized controlled study [ISRCTN23032971].

BACKGROUND: A circadian rhythm of symptoms has been reported in allergic rhinitis and some studies have shown the dosing time of antihistamines to be of importance for optimizing symptom relief in this disease. The objective of this study was to examine the efficacy of morning vs. evening dosing of the antihistamine desloratadine at different time points during the day. METHODS: Patients >/= 18 years, with seasonal allergic rhinitis received desloratadine 5 mg orally once daily in the morning (AM-group) or evening (PM-group) for two weeks. Rhinorrhea, nasal congestion, sneezing and eye symptoms were scored morning and evening. Wilcoxon rank sum and 2-way ANOVA test were used. RESULTS: Six-hundred and sixty-three patients were randomized; 336 in the AM-group; 327 in the PM-group. No statistically significant differences were seen between the AM and PM group at any time points. In the sub-groups with higher morning or evening total symptom score no difference in treatment efficacy was seen whether the dose was taken 12 or 24 hours before the higher score time. There was a circadian variation in baseline total symptom score; highest during daytime and lowest at night. The circadian variation in symptoms was reduced during treatment. This reduction was highest for daytime symptoms. CONCLUSIONS: A circadian rhythm was seen for most symptoms being more pronounced during daytime. This was less apparent after treatment with desloratadine. No statistically significant difference in efficacy was seen whether desloratadine was given in the morning or in the evening. This gives the patients more flexibility in choosing dosing time.

Conjugated linoleic acid supplementation for 1 y reduces body fat mass in healthy overweight humans.

BACKGROUND: Short-term trials showed that conjugated linoleic acid (CLA) may reduce body fat mass (BFM) and increase lean body mass (LBM), but the long-term effect of CLA was not examined. OBJECTIVE: The objective of the study was to ascertain the 1-y effect of CLA on body composition and safety in healthy overweight adults consuming an ad libitum diet. DESIGN: Male and female volunteers (n = 180) with body mass indexes (in kg/m(2)) of 25-30 were included in a double-blind, placebo-controlled study. Subjects were randomly assigned to 3 groups: CLA-free fatty acid (FFA), CLA-triacylglycerol, or placebo (olive oil). Change in BFM, as measured by dual-energy X-ray absorptiometry, was the primary outcome. Secondary outcomes included the effects of CLA on LBM, adverse events, and safety variables. RESULTS: Mean (+/- SD) BFM in the CLA-triacylglycerol and CLA-FFA groups was 8.7 +/- 9.1% and 6.9 +/- 9.1%, respectively, lower than that in the placebo group (P < 0.001). Subjects receiving CLA-FFA had 1.8 +/- 4.3% greater LBM than did subjects receiving placebo (P = 0.002). These changes were not associated with diet or exercise. LDL increased in the CLA-FFA group (P = 0.008), HDL decreased in the CLA-triacylglycerol group (P = 0.003), and lipoprotein(a) increased in both CLA groups (P < 0.001) compared with month 0. Fasting blood glucose concentrations remained unchanged in all 3 groups. Glycated hemoglobin rose in all groups from month 0 concentrations, but there was no significant difference between groups. Adverse events did not differ significantly between groups. CONCLUSION: Long-term supplementation with CLA-FFA or CLA-triacylglycerol reduces BFM in healthy overweight adults.

Efficacy and tolerability of mirabegron, a ß(3)-adrenoceptor agonist, in patients with overactive bladder: results from a randomised European-Australian phase 3 trial.

BACKGROUND: Mirabegron, a ß(3)-adrenoceptor agonist, has been developed for the treatment of overactive bladder (OAB). OBJECTIVE: To assess the efficacy and tolerability of mirabegron versus placebo. DESIGN, SETTING, AND PARTICIPANTS: Multicenter randomised double-blind, parallel-group placebo- and tolterodine-controlled phase 3 trial conducted in 27 countries in Europe and Australia in patients ≥ 18 yr of age with symptoms of OAB for ≥ 3 mo. INTERVENTION: After a 2-wk single-blind placebo run-in period, patients were randomised to receive placebo, mirabegron 50mg, mirabegron 100mg, or tolterodine extended release 4 mg orally once daily for 12 wk. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patients completed a micturition diary and quality-of-life (QoL) assessments. Co-primary efficacy end points were change from baseline to final visit in the mean number of incontinence episodes and micturitions per 24h. The primary comparison was between mirabegron and placebo with a secondary comparison between tolterodine and placebo. Safety parameters included adverse events (AEs), laboratory assessments, vital signs, electrocardiograms, and postvoid residual volume. RESULTS AND LIMITATIONS: A total of 1978 patients were randomised and received the study drug. Mirabegron 50-mg and 100-mg groups demonstrated statistically significant improvements (adjusted mean change from baseline [95% confidence intervals]) at the final visit in the number of incontinence episodes per 24h (-1.57 [-1.79 to -1.35] and -1.46 [-1.68 to -1.23], respectively, vs placebo -1.17 [-1.39 to -0.95]) and number of micturitions per 24h (-1.93 [-2.15 to -1.72] and -1.77 [-1.99 to -1.56], respectively, vs placebo -1.34 [-1.55 to -1.12]; p<0.05 for all comparisons). Statistically significant improvements were also observed in other key efficacy end points and QoL outcomes. The incidence of treatment-emergent AEs was similar across treatment groups. The main limitation of this study was the short (12-wk) duration of treatment. CONCLUSIONS: Mirabegron represents a new class of treatment for OAB with proven efficacy and good tolerability. TRIAL IDENTIFICATION: This study is registered at ClinicalTrials.gov, identifier NCT00689104.

Six months supplementation with conjugated linoleic acid induces regional-specific fat mass decreases in overweight and obese.

Long-term supplementation with conjugated linoleic acid (CLA) reduces body fat mass (BFM) and increases or maintains lean body mass (LBM). However, the regional effect of CLA was not studied. The study aimed to evaluate the effect of CLA per region and safety in healthy, overweight and obese adults. A total of 118 subjects (BMI: 28-32 kg/m2) were included in a double blind, placebo-controlled trial. Subjects were randomised into two groups supplemented with either 3 x 4 g/d CLA or placebo for 6 months. CLA significantly decreased BFM at month 3 (Delta=- 0 x 9 %, P=0 x 016) and at month 6 (Delta=- 3 x 4 %, P=0 x 043) compared with placebo. The reduction in fat mass was located mostly in the legs (Delta=- 0 x 8 kg, P<0 x 001), and in women (Delta=-1 x 3 kg, P=0 x 046) with BMI >30 kg/m2 (Delta=-1 x 9 kg, P=0 x 011), compared with placebo. The waist-hip ratio decreased significantly (P=0 x 043) compared with placebo. LBM increased (Delta=+0 x 5 kg, P=0 x 049) within the CLA group. Bone mineral content was not affected (P=0 x 70). All changes were independent of diet and physical exercise. Safety parameters including blood lipids, inflammatory and diabetogenic markers remained within the normal range. Adverse events did not differ between the groups. It is concluded that supplementation with CLA in healthy, overweight and obese adults decreases BFM in specific regions and is well tolerated.

Supplementation with conjugated linoleic acid for 24 months is well tolerated by and reduces body fat mass in healthy, overweight humans.

After 12 mo in a randomized, double-blind, placebo-controlled trial of conjugated linoleic acid (CLA) supplementation (2 groups received CLA as part of a triglyceride or as the free fatty acid, and 1 group received olive oil as placebo), 134 of the 157 participants who concluded the study were included in an open study for another 12 mo. The goals of the extension study were to evaluate the safety [with clinical chemistry analyses and reported adverse events (AEs)] and assess the effects of CLA on body composition [body fat mass (BFM), lean body mass (LBM), bone mineral mass (BMM)], body weight, and BMI. All subjects were supplemented with 3.4g CLA/d in the triglyceride form. Circulating lipoprotein(a) and thrombocytes increased in all groups. There was no change in fasting blood glucose. Aspartate amino transferase, but not alanine amino transferase, increased significantly. Plasma total cholesterol and LDL cholesterol were reduced, whereas HDL cholesterol and triglycerides were unchanged. The AE rate decreased compared with the first 12 mo of the study. Body weight and BFM were reduced in the subjects administered the placebo during the initial 12 mo study (-1.6 +/- 3.2 and -1.7 +/- 2.8 kg, respectively). No fat or body weight changes occurred in the 2 groups given CLA during the initial 12 mo. LBM and BMM were not affected in any of the groups. Changes in body composition were not related to diet and/or training. In conclusion, this study shows that CLA supplementation for 24 mo in healthy, overweight adults was well tolerated. It confirms also that CLA decreases BFM in overweight humans, and may help maintain initial reductions in BFM and weight in the long term.

Validation of a simple patient questionnaire to assist self-detection of overactive bladder. A study in general practice.

OBJECTIVE: To develop and validate a simple patient questionnaire for the detection of overactive bladder (OAB). DESIGN: An open, non-randomized multicentre study. SETTING: A pilot study (n = 133) was conducted to bring forward five questions from initially 14 questions, for detection of OAB. These five questions were subject to further validation in the main study (n =520). SUBJECTS: 531 adults responding to a newspaper advertisement regarding symptoms of OAB and patients seeing a physician for other reasons were attending 28 general practitioners. MAIN OUTCOME MEASURES: Agreement rate, sensitivity, and specificity. RESULTS: The agreement rate between the patients' own diagnosis based on the patient questionnaire, and the physicians' diagnosis based on medical history, urine analysis, and micturition chart, was 0.78 (kappa =0.89). Sensitivity and specificity were 0.98 and 0.90, respectively. CONCLUSION: The validated questionnaire may become a useful tool to decide whether a patient has overactive bladder. The questionnaire corresponds well with the physicians' diagnosis.