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PubMed | Pfizer, European Service Center, University of Alberta, Groupe Hospitalier Diaconess Croix Saint Simon Urology and 3 more.
Type: | Journal: Age and ageing | Year: 2017

overactive bladder (OAB) is a common condition in older persons. Antimuscarinic treatment remains the mainstay of treatment of OAB but clinicians have been reluctant to prescribe this to older patients. This study examined efficacy and safety information from patients >65 in fesoterodine trials to reaffirm efficacy and to explore the relationships between treatment emergent adverse events (TEAEs), coexisting medication and co-morbidity.data from 10 double-blind, placebo-controlled studies were analysed. A logistic regression analysis, where TEAE incidence was predicted by treatment, prior antimuscarinic treatment, number of coexisting medications, number of concomitant diseases and all possible combinations of two-way interaction terms with treatment was conducted.of 4,040 patients who participated in trials; fesoterodine treatment was associated with statistically significant reductions in all disease-related and patient-reported outcomes compared to placebo. There was a significant increase in the likelihood of reporting a TEAE in association with the number of coexistent medications (odds ratio (OR) = 1.028, 95% CI: 1.0143-1.044, P < 0.003). The OR of having a TEAE with increase in the number of concomitant diseases was 1.058 (95% CI: 1.044-1.072, P < 0.0001). Central nervous system (CNS) events were few.fesoterodine treatment led to clinically meaningful improvements across all included patient reported outcomes. The number of concomitant conditions had the greatest influence on the likelihood of an adverse event being reported. CNS TEAE were not associated with fesoterodine dose and were low across all categories of concomitant disease and coexisting medication.

Sidhu P.,The Royal Veterinary College | Sidhu P.,Guru Angad Dev Veterinary and Animal Sciences University | Rassouli A.,The Royal Veterinary College | Rassouli A.,University of Tehran | And 7 more authors.
Journal of Veterinary Pharmacology and Therapeutics | Year: 2014

Florfenicol was administered subcutaneously to 10 calves at a dose of 40 mg/kg. Pharmacokinetic-pharmacodynamic (PK-PD) integration and modelling of the data were undertaken using a tissue cage model, which allowed comparison of microbial growth inhibition profiles in three fluids, serum, exudate and transudate. Terminal half-lives were relatively long, so that florfenicol concentrations were well maintained in all three fluids. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration were determined in vitro for six strains each of the calf pneumonia pathogens, Mannhemia haemolytica and Pasteurella multocida. An PK-PD integration for three serum indices provided mean values for P. multocida and M. haemolytica, respectively, of 12.6 and 10.4 for Cmax/MIC, 183 and 152 h for AUC0-24 h/MIC and 78 and 76 h for T>MIC. Average florfenicol concentrations in serum exceeded 4 × MIC and 1.5 × MIC for the periods 0-24 and 48-72 h, respectively. Ex vivo growth inhibition curves for M. haemolytica and P. multocida demonstrated a rapid (with 8 h of exposure) and marked (6 log10 reduction in bacterial count or greater) killing response, suggesting a concentration-dependent killing action. During 24-h incubation periods, inhibition of growth to a bacteriostatic level or greater was maintained in serum samples collected up to 96 h and in transudate and exudate samples harvested up to 120 h. Based on the sigmoidal Emax relationship, PK-PD modelling of the ex vivo time-kill data provided AUC0-24 h/MIC serum values for three levels of growth inhibition, bacteriostatic, bactericidal and 4 log10 decrease in bacterial count; mean values were, respectively, 8.2, 26.6 and 39.0 h for M. haemolytica and 7.6, 18.1 and 25.0 h for P. multocida. Similar values were obtained for transudate and exudate. Based on pharmacokinetic and PK-PD modelled data obtained in this study and scientific literature values for MIC distributions, Monte Carlo simulations over 100 000 trials were undertaken to predict once daily dosages of florfenicol required to provide 50% and 90% target attainment rates for three levels of growth inhibition, namely, bacteriostasis, bactericidal action and 4 log10 reduction in bacterial count. © 2013 John Wiley & Sons Ltd.

PubMed | National Institute for Public Health and the Environment, University Utrecht, Medical Center Haaglanden, Public Health Service Haaglanden and 7 more.
Type: | Journal: Emerging themes in epidemiology | Year: 2014

In May 2014, Middle East respiratory syndrome coronavirus (MERS-CoV) infection, with closely related viral genomes, was diagnosed in two Dutch residents, returning from a pilgrimage to Medina and Mecca, Kingdom of Saudi Arabia (KSA). These patients travelled with a group of 29 other Dutch travellers. We conducted an epidemiological assessment of the travel group to identify likely source(s) of infection and presence of potential risk factors.All travellers, including the two cases, completed a questionnaire focussing on potential human, animal and food exposures to MERS-CoV. The questionnaire was modified from the WHO MERS-CoV questionnaire, taking into account the specific route and activities of the travel group.Twelve non-cases drank unpasteurized camel milk and had contact with camels. Most travellers, including one of the two patients (Case 1), visited local markets, where six of them consumed fruits. Two travellers, including Case 1, were exposed to coughing patients when visiting a hospital in Medina. Four travellers, including Case 1, visited two hospitals in Mecca. All travellers had been in contact with Case 1 while he was sick, with initially non-respiratory complaints. The cases were found to be older than the other travellers and both had co-morbidities.This epidemiological study revealed the complexity of MERS-CoV outbreak investigations with multiple potential exposures to MERS-CoV reported such as healthcare visits, camel exposure, and exposure to untreated food products. Exposure to MERS-CoV during a hospital visit is considered a likely source of infection for Case 1 but not for Case 2. For Case 2, the most likely source could not be determined. Exposure to MERS-CoV via direct contact with animals or dairy products seems unlikely for the two Dutch cases. Furthermore, exposure to a common but still unidentified source cannot be ruled out. More comprehensive research into sources of infection in the Arabian Peninsula is needed to strengthen and specify the prevention of MERS-CoV infections.

Marignier R.,European Service Center | Giraudon P.,University of Lyon | Vukusic S.,European Service Center | Confavreux C.,European Service Center | Honnorat J.,University of Lyon
Therapeutic Advances in Neurological Disorders | Year: 2010

Devic's neuromyelitis optica (DNMO) is a demyelinating and inflammatory disease of the central nervous system (CNS) essentially restricted to the spinal cord and the optic nerves. It is a rare disorder with a prevalence estimated at less than 1/100,000 in Western countries. Since the first description by Eugène Devic in 1894, the relationship between DNMO and multiple sclerosis (MS) has been controversial. Recent clinical, epidemiological, pathological and immunological data demonstrate that MS and DNMO are distinct entities. This distinction between DNMO and MS is crucial, as prognosis and treatment are indeed different. DNMO is now considered to be an autoimmune, antibody-mediated disease especially since the identification of a specific serum autoantibody, named NMO-IgG and directed against the main water channel of the CNS, aquaporin-4 (AQP4). The assessment of AQP4 antibodies (Abs) has initially been proposed to differentiate DNMO and MS. It has also enlarged the clinical spectrum of DNMO and proved to be helpful in predicting relapses and conversion to DNMO after a first episode of longitudinally extensive transverse myelitis or isolated optic neuritis. Lastly, the discovery of the pathogenic role of AQP4 Abs in DNMO leads to a better understanding of detailed DNMO immunopathology and the elaboration of relevant novel treatment strategies specific to DNMO. In this review, we summarize the present and future therapeutic implications generated by the discovery of the various pathogenic mechanisms of AQP4 Abs in DNMO pathophysiology. © The Author(s), 2010.

Potter T.,Royal Veterinary College | Potter T.,Westpoint Veterinary Group | Illambas J.,Royal Veterinary College | Illambas J.,European Service Center | And 3 more authors.
Veterinary Journal | Year: 2013

The pharmacokinetics (PK) and pharmacodynamics (PD) of marbofloxacin were established in calves for six strains of each of the pneumonia pathogens Mannheimia haemolytica and Pasteurella multocida. The distribution of marbofloxacin into inflamed (exudate) and non-inflamed (transudate) tissue cage fluids allowed comparison with the serum concentration-time profile. To establish the PD profile, minimum inhibitory concentration (MIC) was determined in Mueller-Hinton broth (MHB) and calf serum.Moderately higher MICs were obtained for serum compared to MHB. An initial integration of PK-PD data established Cmax/MIC ratios of 45.0 and AUC24h/MIC values of 174.7h, based on serum MICs, for both bacterial species. Using bacterial time-kill curves, generated ex vivo for serum marbofloxacin concentrations, PK-PD modelling established three levels of growth inhibition: AUC24h/MIC ratios for no reduction, 3 log10 and 4 log10 reductions in bacterial count from the initial inoculum count were 41.9, 59.5 and 68.0h for M. haemolytica and 48.6, 64.9 and 74.8h for P. multocida, on average respectively. Inter-strain variability for 3 log10 and 4 log10 reductions in bacterial count was smaller for P. multocida than for M. haemolytica. In conjunction with literature data on MIC90 values, the present results allowed prediction of dosages for efficacy for each organism for the three levels of growth inhibition. © 2012 Elsevier Ltd.

Knezevic S.,Institute of Meteorology | Tosic I.,Institute of Meteorology | Unkasevic M.,Institute of Meteorology | Pejanovic G.,European Service Center
Theoretical and Applied Climatology | Year: 2014

In this study, the influence of the East Atlantic Oscillation (EAO) on the climate indices based on the daily minimum temperature at eight stations in Serbia was examined. The following climate indices were analyzed: frost days (FD), cold nights (TN10p), warm nights (TN90p), minimum value of daily minimum temperature (TNn), tropical nights (TR), and cold spell duration indice (CSDI). Analysis of correlation between the East Atlantic Index (EAI) and the geopotential at 500 hPa, as well as between the EAI and climate indices was realized for all seasons and months during the period 1950-2009. Two characteristic situations for the extreme positive and negative values of the EAI were analyzed. Seasonal and monthly trend analyses of climate indices were performed. Decreases of FD and TN10p and increases of TN90p and TR were observed. It was found that the negative correlation prevailed between the EAI and TN10p/FD, and positive one between the EAI and TN90p/TR for all seasons and months. The highest correlation was observed between the EAI and TN90p in February. © 2013 Springer-Verlag Wien.

Testa C.,European Service Center
PPCJ Polymers Paint Colour Journal | Year: 2012

An experiment was conducted to demonstrate that Texanol ester alcohol significantly improves the wet scrub resistance of matte interior wall paints applied at temperatures above the polymer's glass transition temperature (T g). The formulated paints were based on Acronal S 790, a styrene acrylic binder from BASF, with a Tg of 22°C and W673 a Va/VeoVa binder from Synthomer, with a Tg of 14°C. The two paints were divided into three parts. Two parts had Texanol added at 0.57% and 1.16% on total weight of paint; and the third sample had no coalescent added. The wet scrub resistance of the paints was determined via the ASTM D2486 method to assess the integrity of the films formed at the varying application temperatures after two and six weeks. Wet scrub resistance was improved when paint was applied at temperatures that were higher than the Tg of the polymers.

PubMed | European Service Center
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016

e14018 Background: Malnutrition (MN) could reduce survival, tolerance and response to treatment, as well as quality of life of patients (pts) in numerous cancers. Data involving mCRC are scarce and often outdated. The purpose of this study was to evaluate, in mCRC pts, the effect of MN on survival and tolerance to modern chemotherapeutic regimens, and to identify a suitable measurement method to assess their nutritional status.In this prospective, multicentric study, demographic, oncologic and nutritional data, including various nutritional indexes already used in cancerology (Nutritional Risk Index [NRI], Prognostic Inflammatory and Nutritional Index [PINI], nutritional evaluation according to the French National Accreditation and Evaluation in Health Agency [ANAES] and weight loss during the past six months [ weight]) were prospectively collected in all mCRC consecutive pts for 15 days in 8 hospitals in France. Chemotherapy related toxicities were graded according to the NCI-CTC, V3.0. Survivals were calculated (Kaplan Meier) and compared (log Rank). Cox univariate models were used to study and compare the prognostic significance of the indexes.114 mCRC pts (median age: 65 [22; 92] years) participated to the study. Malnutrition occurred in 32 to 65% of pts, and severe malnutrition in 15 to 19%, depending on the score used to assess it. Severe malnutrition, as defined by a weight >15% during the last 6 months, was, above all other indexes, strongly correlated to survival. It was associated with a decreased median overall survival (16.8 months [IC95% : 7.2-37.2] vs 37.2 months [30-42] in non-malnourished patients, HR= 2.03, [IC95%: 1.04-3.99], p=0.04) and to an increased rate of grade 2 toxicities (88% vs 56%, p=0.03) in the two months following this nutritional assessment.In mCRC pts, malnutrition seems to be relatively frequent and associated with reduced overall survival and increased chemotherapy-induced toxicities. weight appears as a simple and reliable nutritional tool to detect and evaluate malnutrition in daily practice in this population.

PubMed | European Service Center
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016

4033 Background: The standard treatment for advanced HCC is sorafenib. However this treatment does not induce tumor shrinkage and allows a modest improvement in overall survival (OS) and progression-free survival (PFS). For 10 years, we have developed a regimen of combined systemic chemotherapy with gemcitabine and oxaliplatin (GemOx regimen) which provides adequate control of the disease with manageable toxicity. We report our experience on > 200 patients (pts) consecutively treated with this regimen.This retrospective multicenter study included all consecutive pts treated for advanced HCC with GemOx. Survival curves were drawn with the Kaplan-Meier method and compared by the log-rank test. Models of univariate and multivariate analyses were used to search for prognostic and predictive factors of therapeutic efficacy and OS.210 pts were enrolled from 2001 to 2010. 190 pts are currently with complete data collection. Average age: 60 years (20-83), M / F: 164/26, metastatic stage: 36%, underlying cirrhosis: 86%, Child Pugh score A: 75 % B: 21%, C: 4%, median CLIP score: 3 (0-5), WHO Performance status 0/1/2/3: 34/49/15/2 %. The objective response rate (OR: complete response + partial response) was 21% (WHO criteria) and disease control rate (DCR: OR + stable disease) was 62 %. The median PFS and OS were 6 (95% CI: 4.5 to 10) and 10.5 (95% CI: 9-13) months, respectively. Ten pts were eligible for curative surgery and 5 for secondary closure treatment which were not possible before GemOx treatment. In univariate and multivariate analyses, only the absence of underlying cirrhosis was significantly associated with better OR and OS. OR was significantly associated with a longer median OS (14 vs 6 months, p = 0 .019). OR prognostic value on survival was confirmed in multivariate analysis (HR = 0.46, 95% CI [0.32 to 0.73], p = 0.002).The results reported in this series involving more than 200 consecutive pts suggest the efficacy of the GemOx regimen in advanced HCC patients and the opportunity it offers in about 10% of pts for secondary curative-intent therapies. The final results of this work will be presented at the meeting.

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