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A quantitative method for the simultaneous determination of docetaxel (Taxotere), paclitaxel (Taxol), 6[alpha]-hydroxypaclitaxel, and p-3'-hydroxypaclitaxel in human plasma and oral fluid is developed and validated. Oral fluid (this term is now preferred to saliva) was sampled with a Salivette collection device. The procedure used a simple liquid/liquid extraction with methyl tert-butyl ether followed by LC-ESI-MS/MS. Gradient elution was applied and provided increased robustness to ion suppression by the drug formulation vehicle (polysorbate 80 and Cremophor EL). Adduct ion formation with sodium and potassium was noticed and controlled by mobile-phase optimization. The protonated analytes generated in the positive ion mode were monitored through multiple reaction monitoring. Calibration was performed by internal standardization with cephalomannine, and regression curves were constructed ranging between 2 and 1000 ng/mL in plasma and 0.125 and 62.5 ng/mL in oral fluid, using a weighing factor of 1/[x.sup.2]. The regression curves were quadratic for paclitaxel and docetaxel and linear for the paclitaxel metabolites. Accuracy varied from 91.3 to 103.6%, and imprecision did not exceed 12.7% for all analytes in plasma and oral fluid. In conclusion, a sensitive and robust method was obtained, which fulfilled all validation criteria.

Background: Direct oral anticoagulants (DOACs) account for an increasing proportion of prescriptions in patients with non-valvular atrial fibrillation (NVAF) in primary care. Inappropriate dosing of DOACs is a common problem, with under-dosing being a particular issue. However, conflicting results have been reported about the factors independently associated with inappropriate dosing.Aim: To describe inappropriate prescriptions of DOACs among patients in the CACAO French nationwide general practice cohort, and to identify the factors independently associated with inappropriate DOAC doses.Design and Setting: Cross-sectional baseline analysis of the CACAO French national multicentre prospective cohort of adult patients in primary care receiving an oral anticoagulant who were recruited between April and October 2014.Method: A total of 1111 patients from the CACAO cohort who received a DOAC for NVAF were included in this study. Inappropriate prescriptions of DOACs were described (inappropriate dosage, contraindications, non-indications, interactions, and non-compliance with the precautions for use). Multivariate logistic models were used to investigate factors associated with inappropriate DOAC dosing (under-dosing and over-dosing).Results: Overall, 438 patients (39.4%) received at least one inappropriate DOAC prescription. The most common inappropriate prescription was inappropriate dosage (n = 374, 33.7%), particularly under-dosing (n = 348, 31.3%). Multivariate analysis revealed that factors independently associated with under-dosing were older age, prescription of apixaban or dabigatran, and a CHA2DS2-VASc score ≥2 vs. a score = 1. Factors with over-dosing were kidney failure, a HAS-BLED score ≥3, and older age.Conclusion: The appropriateness of DOAC prescribing for NVAF can be improved, especially in older patients, and in patients with kidney failure, a higher risk of ischaemic stroke, and/or a higher risk of bleeding. GPs have a key role in increasing the proportion of appropriate DOAC prescriptions via informational, educational, and/or management strategies. [ABSTRACT FROM AUTHOR]

Background: Underdiagnosis and undertreatment of chronic heart failure (CHF) are common in older patients, who are usually treated by general practitioners (GPs). In 2007, the French ICAGE study explored GPs' attitudes to the management of this condition in older patients.Objectives: To explore changes over time in GPs' attitudes towards the management of CHF in patients aged ≥75 and to identify barriers to optimal management.Methods: In 2015, we performed a qualitative study of 20 French GPs via semi-structured interviews and a thematic content analysis. The results were compared with the findings of a 2007 study.Results: In 2015, the perceived barriers to diagnosis were the same as in 2007. Echocardiography was still the preferred diagnostic method but the GPs relied on the cardiologist to confirm the diagnosis. Many GPs were still unaware of the different types of CHF. In contrast, they reported greater knowledge of decompensation factors and the ultrasound criteria for CHF. They also prescribed a brain natriuretic peptide assay more frequently. Angiotensin-converting enzyme inhibitors and beta blockers were more strongly perceived to be core treatments. Few GPs initiated drug treatments and optimized dosages. Although patient education was never mentioned, the importance of multidisciplinary care was emphasized.Conclusion: Our results evidenced a small recent improvement in the management of older patients with CHF. Appropriate guidelines and training for GPs, patient education and multidisciplinary collaboration might further improve the care given to this population. [ABSTRACT FROM AUTHOR]

Background: No study has investigated factors associated with non-participation or partial participation in the different combination patterns of screening programmes for all three cancers, that is, breast, colorectal and cervical cancer.Methods: In a retrospective cohort study, we sought to describe combinations of cancer screening participation rates among women in the Val-de-Marne area of France and to identify individual and contextual factors associated with non-participation or partial participation.Results: Women aged between 50 and 65 and who were eligible for all three screening programmes (n = 102 219) were analysed in multilevel logistic models, with the individual as the Level 1 variable and the place of residence as the Level 2 variable. The women who did not participate in any of the screening programmes were 34.4%, whereas 30.1%, 24% and 11.5% participated in one, two or all three screening programmes, respectively. Age below 55, a previous false-positive mammography, prior opportunistic mammography only, no previous mammography, membership of certain health insurance schemes (all P < 0.05) and residence in a deprived area (P < 0.001) were independently associated with non-participation or partial participation. We observed a stronger effect of deprivation on non-participation in all three cancers than in combinations of screening programmes.Conclusion: Our findings suggest that the health authorities should focus on improving cancer screenings in general rather than screenings for specific types of cancer, especially among younger women and those living in the most socially deprived areas. [ABSTRACT FROM AUTHOR]