Subjective health status and health-related quality of life among women with Recurrent Vulvovaginal Candidosis (RVVC) in Europe and the USA

Abstract Background Recurrent vulvovaginal candidosis (RVVC) is a chronic condition causing discomfort and pain. Health status and health-related quality of life (HRQoL) in RVVC were never previously described using validated questionnaires. The objective of this study is to describe subjective health status and HRQoL and estimate health state utilities among women with RVVC. Methods A cross-sectional online survey was conducted among women who reported having suffered four or more yeast infections over the past 12 months, in five European countries (France, Germany, Italy, Spain and the UK) and the USA. Index scores were derived from the EQ-5D, a questionnaire providing a single index value for health status. The SF-36 questionnaire was used for HRQoL assessment. Information on disease severity, treatment patterns and productivity was also collected. Results 12,834 members of online research panels were contacted. Among them, 620 women with RVVC (5%) were selected to complete the full questionnaire. The mean EQ-5D index score was 0.70 (95% confidence interval: [0.67, 0.72]) and the difference between women with a yeast infection at the time of questionnaire completion and other respondents was 0.05 (p = 0.47). The EQ-5D index score increased significantly with the time since last infection (p \u3c 0.001). 68% of women reported depression/anxiety problems during acute episode, and 54% outside episodes, compared to less than 20% in general population (p \u3c 0.001). All SF-36 domain scores were significantly below general population norms. Mental health domains were the most affected. The impact on productivity was estimated at 33 lost work hours per year on average, corresponding to estimated costs between €266/year and €1,130/year depending on the country. Conclusions Subjective health status and HRQoL during and in between acute inflammatory episodes in women with RVVC are significantly worse than in the general population, despite the use of antifungal therapy. The average index score in women with RVVC is comparable to other diseases such as asthma or COPD and worse than diseases such as headache/migraine according to US and UK catalogs of index scores. The survey also revealed a significant loss of productivity associated with RVVC

A retrospective study of treatment persistence and adherence to mirabegron versus antimuscarinics, for the treatment of overactive bladder in Spain.

Persistence on-treatment with antimuscarinics in patients with overactive bladder (OAB) is reported to be sub-optimal. This retrospective, longitudinal, observational cohort study assessed treatment persistence with β3-adrenoceptor agonists (i.e. mirabegron) and antimuscarinics, both classes of OAB pharmacotherapy, in patients with OAB in Spain.Adults who received mirabegron or an antimuscarinic in routine clinical practice (1 June-31 October 2014), were identified from anonymised prescription data within the Spanish Cegedim Electronic Medical Records database. The primary endpoint, treatment persistence (time to treatment discontinuation [TTD] and the proportion of patients remaining on-treatment after 12 months), was unadjusted for potential confounders. Multivariate Cox regression models of persistence, adjusted for baseline characteristics, were used to compare differences in treatment groups. Adjusted subgroup analyses (target OAB drug, age, treatment status and sex) and sensitivity analyses (extending the time used to define treatment discontinuation from 30 days [base-case] to 45, 60 or 90 days without prescription renewal) were also performed.Overall, 1798 patients received mirabegron (N = 1169) or an antimuscarinic (N = 629); the mean age was 66.42 years. Median TTD was longer for mirabegron versus antimuscarinics (90 vs 56 days) and a higher proportion of patients who received mirabegron were persistent after 12 months (20.2% vs 10.2%); multivariate analyses indicated significantly greater persistence with mirabegron versus antimuscarinics (hazard ratio [HR]: 1.52; 95% confidence interval [CI]: 1.37-1.70; p < 0.001). Significant differences were also observed in subgroup analyses of mirabegron versus individual antimuscarinics (median TTD: 90 vs [range] 28-60 days; HR range: 1.21-2.17; p ≤ 0.013) and in all other subgroups assessed (p < 0.001). Sensitivity analysis showed that the median TTD for mirabegron increased by up to 31 days, and was significantly longer versus antimuscarinics across all adjusted periods (HR range: 1.43-1.53; all p < 0.001).Patients with OAB in Spain who received mirabegron experienced longer persistence on-treatment than those who received antimuscarinics and the proportion of patients persistent on-treatment at 12 months with mirabegron was two-times higher versus antimuscarinics. These data may provide strategic insights for clinicians and policy makers involved in the management of OAB

Persistence and Adherence with Mirabegron versus Antimuscarinic Agents in Patients with Overactive Bladder: A Retrospective Observational Study in UK Clinical Practice

Background: Persistence with antimuscarinic therapy in overactive bladder (OAB) is poor, but may be different for mirabegron, a β3-adrenoceptor agonist with a different adverse event profile. Objective: To compare persistence and adherence with mirabegron versus tolterodine extended release (ER) and other antimuscarinics in routine clinical practice over a 12-mo period. Design, setting, and participants: Retrospective, longitudinal, observational study of anonymised data from the UK Clinical Practice Research Datalink GOLD database. Eligibility: age ≥18 yr, ≥1 prescription for target OAB drug (between May 1, 2013 and June 29, 2014), and 12-mo continuous enrolment before and after the index prescription date. Interventions: Mirabegron, darifenacin, fesoterodine, flavoxate, oxybutynin ER or immediate-release (IR), propiverine, solifenacin, tolterodine ER or IR, and trospium chloride. Outcome measurements and statistical analysis: The primary endpoint was persistence (time to discontinuation). Secondary endpoints included 12-mo persistence rates and adherence (assessed using medication possession ratio, MPR). Cox proportional-hazards regression models and logistic regression models adjusted for potential confounding factors were used to compare cohorts. Analyses were repeated after 1:1 matching. Results and limitations: The study population included 21. 996 eligible patients. In the unmatched analysis, the median time-to-discontinuation was significantly longer for mirabegron (169 d, interquartile range [IQR] 41-not reached) compared to tolterodine ER (56 d, IQR 28-254; adjusted hazard ratio [HR] 1.55, 95% confidence interval 1.41-1.71; p <. 0.0001) and other antimuscarinics (range 30-78 d; adjusted HR range 1.24-2.26, p <. 0.0001 for all comparisons). The 12-mo persistence rates and MPR were also significantly greater with mirabegron than with all the antimuscarinics. Limitations include the retrospective design, use of prescription records to estimate outcomes, and inability to capture reasons for discontinuation. Conclusions: Persistence and adherence were statistically significantly greater with mirabegron than with tolterodine ER and other antimuscarinics prescribed for OAB in the UK. Patient summary: This study assessed persistence and adherence (or compliance) with medications prescribed for OAB in a large UK population. We found that patients prescribed mirabegron remained on treatment for longer and showed greater adherence than those prescribed traditional antimuscarinics. For chronic conditions such as overactive bladder, long-term adherence is important to maintain treatment benefit. Persistence with antimuscarinics is a recognised challenge. This analysis of a UK primary care database demonstrates that persistence and adherence are significantly greater with mirabegron versus antimuscarinics

Vérification formelle d'un réseau sur puce : Application de DEv-Promela.

National audienc

Limiting State Space Explosion of Model Checking Using Discrete Event Simulation : Combining DEVS and PROMELA

International audienc

IMPROVING BUSINESS PROCESS IN SEMICONDUCTOR MANUFACTURING BY DISCOVERING BUSINESS RULES

International audienc

Limiting State Space Explosion of Model Checking Using Discrete Event Simulation : Combining DEVS and PROMELA

International audienc

Escherichia coli response to uranyl exposure at low pH and associated protein regulations.

Better understanding of uranyl toxicity in bacteria is necessary to optimize strains for bioremediation purposes or for using bacteria as biodetectors for bioavailable uranyl. In this study, after different steps of optimization, Escherichia coli cells were exposed to uranyl at low pH to minimize uranyl precipitation and to increase its bioavailability. Bacteria were adapted to mid acidic pH before exposure to 50 or 80 µM uranyl acetate for two hours at pH≈3. To evaluate the impact of uranium, growth in these conditions were compared and the same rates of cells survival were observed in control and uranyl exposed cultures. Additionally, this impact was analyzed by two-dimensional differential gel electrophoresis proteomics to discover protein actors specifically present or accumulated in contact with uranium.Exposure to uranium resulted in differential accumulation of proteins associated with oxidative stress and in the accumulation of the NADH/quinone oxidoreductase WrbA. This FMN dependent protein performs obligate two-electron reduction of quinones, and may be involved in cells response to oxidative stress. Interestingly, this WrbA protein presents similarities with the chromate reductase from E. coli, which was shown to reduce uranyl in vitro

Cell survival after exposure to uranyl at acidic pH.

<p>Numbering of Colony Forming Units from the <i>E. coli</i> culture in LB-Mes pH 5.5, and in the exposure LB 1/10 Glucose medium at pH 2.7 before (T0) and after exposure for 2 hours to 50 µM sodium acetate, 50 µM of uranyl acetate, and 80 µM of uranyl acetate.</p