Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Pelvic floor muscle training for overactive bladder symptoms – A prospective study

Introduction: Pelvic floor muscle training (PFMT) involves the contraction of the puborectal, anal sphincter and external urethral muscles, inhibiting the detrusor contraction, what justify its use in the treatment of overactive bladder (OAB) symptoms. Objective: To verify the effects of isolated PFMT on the symptoms of OAB. Method: Prospective clinical trial with 27 women with mixed urinary incontinence (MUI), with predominance of OAB symptoms and loss >= 2 g in the pad test. It was evaluated: pelvic floor muscles (PFMs) function (digital palpation and manometry)urinary symptoms (nocturia, frequency and urinary loss)degree of discomfort of OAB symptomsand quality of life (Incontinence Quality-of-Life Questionnaire [I-QoL]). The PFMT program consisted of 24 outpatient sessions (2x/week + home PFMT). The Mann-Whitney and Wilcoxon tests (with a significance level of 5%) were used to analyse the data. Results: There was a significant improvement of the urinary symptoms to the pad test (5.8 +/- 9.7, p<0.001), urinary loss (0.7 +/- 1.1, p=0.005) and nocturia (0.8 +/- 0.9, p=0.011). Reduction in the degree of discomfort of urinary symptoms was observed according to OAB-V8 questionnaire (10.0 +/- 7.7, p=0.001). There were also significant results in PFMs function: Oxford (3.6 +/- 0.9, p=0.001), endurance (5.2 +/- 1.8, p<0.001), fast (8.9 +/- 1.5, p<0.001) and manometry (26.6 +/- 15.8, p=0.003). In addition, quality of life had a significant improvement in the three domains evaluated by I-QoL. Conclusion: The PFMT without any additional guidelines improves the symptomatology, the function of PFMs and the quality of life of women with OAB symptoms.Univ Fed Sao Paulo UNIFESP, Dept Gynecol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Gynecol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo UNIFESP, EPM, Setor Uroginecol & Cirurgia Vaginal, Dept Gynecol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo UNIFESP, Dept Gynecol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Gynecol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo UNIFESP, EPM, Setor Uroginecol & Cirurgia Vaginal, Dept Gynecol, Sao Paulo, SP, BrazilWeb of Scienc

Correlation between maximum voluntary contraction and endurance measured by digital palpation and manometry: An observational study

Introduction: Digital palpation and manometry are methods that can provide information regarding maximum voluntary contraction (MVC) and endurance of the pelvic floor muscles (PFM), and a strong correlation between these variables can be expected. Objective: To investigate the correlation between MVC and endurance, measured by digital palpation and manometry. Method: Forty-two women, with mean age of 58.1 years (+/- 10.2), and predominant symptoms of stress urinary incontinence (SUI), were included. Examination was firstly conducted by digital palpation and subsequently using a Peritron manometer. MVC was measured using a 0-5 score, based on the Oxford Grading Scale. Endurance was assessed based on the PERFECT scheme. Results: We found a significant positive correlation between the MVC measured by digital palpation and the peak manometric pressure (r= 0.579, p< 0.001), and between the measurements of the endurance by Peritron manometer and the PERFECT assessment scheme (r= 0.559, p< 0.001). Conclusion: Our results revealed a positive and significant correlation between the capacity and maintenance of PFM contraction using digital and manometer evaluations in women with predominant symptoms of SUI.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ Fed Sao Paulo Unifesp, Dept Gynecol, Sao Paulo, SP, BrazilDepartment of Gynecology, Universidade Federal de São Paulo (Unifesp), São Paulo, SP, BrazilCNPq: 140190/2013-9Web of Scienc