Usefulness of ß-D-glucan for diagnosis and follow-up of invasive candidiasis in onco-haematological patients.

OBJECTIVES: Definitive diagnosis of invasive candidiasis (IC) may be difficult to achieve in patients with haematological malignancy (PHM). We aimed to evaluate the performance of BDG for the diagnosis and the follow-up of IC in PHM. PATIENTS AND METHODS: We retrospectively reviewed the serological data of BDG assay in adult and paediatric PHM, who developed candidemia or chronic disseminated candidiasis (CDC) through a 4-year period. Sensitivity and kinetics of BDG were determined for both clinical forms. RESULTS: In a panel of 3027 PHM, incidence rates of candidemia and CDC ranged between 0.74 and 0.77 and 0.30 and 0.44 according to the group of patients. At the time of diagnosis, 43.5% and 73% of cases of candidemia and CDC had a positive BDG assay, respectively. We found a significant correlation between the level of BDG at diagnosis and the outcome of candidemia (p = 0.022). In all cases of CDC, BDG negative results were obtained 2 to 6 months before recovery of the CT-scan lesions. CONCLUSIONS: BDG exhibits a low sensitivity to detect IC in PHM, but its kinetics correlates the clinical outcome. Additional studies are warranted in patients with CDC to evaluate the interest of monitoring BDG levels to anticipate the discontinuation of antifungal maintenance therapy.

[Assessment of physicians' and nurses' knowledge and practices of aerosol therapy]. / Évaluation des connaissances et des pratiques de la nébulisation par les soignants.

INTRODUCTION: Aerosol therapy is an efficient, but complex procedure. National and international practice guidelines are regularly updated. However, only a few studies have assessed the application of guidelines by users. The aim of this study is to assess the knowledge and practices of physicians and nurses regarding these guidelines. METHODS: Two self-administered questionnaires were designed by a working team and presented to physicians and nurses of four university hospitals in Paris. A pharmacy resident collected and analyzed the data with the aid of an online survey website. RESULTS: A total of 481 physicians and nurses completed the questionnaires (33 % of physicians and 67 % of nurses). Only 241/480 physicians and nurses (50 %) knew that several intravenous drugs cannot be nebulized. Ninety-four of 422 (22 %) of them always choose oxygen as the driving gas and 239/311 nurses (77 %) think that single use nebulizers can be re-used for the same patient. CONCLUSIONS: This survey shows that many physicians and nurses lack knowledge and use inappropriate practices. Based on these results, a booklet has been designed by the working team. This booklet should help health professionals to harmonize practices across hospitals and to follow the guidelines correctly.

[Assessment of patient needs to design a patient education program in systemic lupus erythematosus]. / Évaluation des attentes des patients pour un programme d'éducation thérapeutique au cours du lupus systémique.

PURPOSE: The aim of this study was to collect information to design a patient education program (PEP) for patients with systemic lupus erythematosus (SLE), based as much as possible on their expectations. PATIENTS AND METHODS: Three different approaches were used for addressing patients' needs: 1) A questionnaire on their expectations in terms of a PEP was sent to the members of SLE associations and offered to patients at the French reference center for SLE, 2) A patients' focus group was conducted, and 3) After the teaching sessions, satisfaction questionnaires were also evaluated. RESULTS: The patients who answered the expectation questionnaire (n=422, women/men sex-ratio: 12.6) indicated a major interest in the PEP (70.4%). Their expectations were broad, and covered the topics of pregnancy (90% of the women under the age of 40), the outcome of the disease (80.8%), the respective roles of the different treatments (70.4%), and also the management of everyday symptoms: fatigue and pain (66.4%). The focus group (eight people) highlighted the need for improving how the diagnosis of the disease was delivered, and also revealed the loneliness and the guilty feeling experienced by some patients toward their relatives. Satisfaction questionnaires confirmed these expectations for the PEP, and even extended them to new topics: the mechanisms behind SLE, travel and leisure, and possible accommodations in the workplace. CONCLUSIONS: The direct consultation of patients with SLE targeted by a specific PEP program allowed us to confirm and adapt the topics and the content of a program designed by medical staff.

[Inhalation devices: characteristics, modeling, regulation and use in routine practice. GAT Aerosolstorming, Paris 2011]. / Les dispositifs d'inhalation : propriétés, modélisation, réglementation et utilisation en pratique courante. Aérosolstorming du GAT, Paris 2011.

Aerosoltherapy is a first-line treatment for chronic obstructive respiratory diseases such as asthma and COPD. Treatment modalities and devices are varied and the choice of the device must be adapted to and optimized for every patient. Spacers can be used for some categories of patients for whom the use of other devices turns out to be complicated. The improvement of these treatments requires the optimization of the lung deposition of inhaled particles; lung modeling plays an essential role in the understanding of the mechanisms of flow in the airways. Regulations must frame prescription of inhaled treatments to optimize its quality and, thus, the care for these chronic diseases. Many generally-accepted ideas concerning these treatments turn out to be false. Inhaled treatments are constantly evolving, both pharmacologically and technologically.

Diclofenac and its derivatives as tools for studying human cytochromes P450 active sites: particular efficiency and regioselectivity of P450 2Cs.

A comparison of the oxidations of diclofenac with microsomes of yeasts expressing various human liver cytochromes P450 showed that P450 2C9 regioselectively led to 4'-hydroxy diclofenac (4'-OHD) whereas P450 3A4 only led to 5-hydroxy diclofenac (5-OHD). P450 2C19, 2C18, and 2C8 led to the simultaneous formation of 4'-OHD and 5-OHD (respective molar ratios of 1.3, 0.37, and 0.17), and P450 1A1, 1A2, 2D6, and 2E1 failed to give any detectable hydroxylated metabolite under identical conditions. P450 2C9 was found to be much more efficient for diclofenac hydroxylation than all the other P450s tested (k(cat)/K(M) of 1.6 min(-1) microM(-1) instead of 0.025 for the second more active P450), mainly because of markedly lower K(M) values (15 +/- 8 instead of values between 170 and 630 microM). Oxidation of diclofenac with chemical model systems of cytochrome P450 based on iron porphyrin catalysts exclusively led to the quinone imine derived from two-electron oxidation of 5-OHD, in an almost quantitative yield. Two derivatives of diclofenac lacking its COO(-) function were then synthesized; their oxidation by recombinant human P450 2Cs always led to a major product coming from their 5-hydroxylation. Substrate 2, which derives from reduction of the COO(-) function of diclofenac to the CH(2)OH function, was studied in more detail. All the P450s tested (1A1, 1A2, 2C8, 2C9, 2C18, 2C19, 2D6, and 3A4) almost exclusively led to its 5-hydroxylation. P450s of the 2C subfamily were found to be the most efficient catalysts for this reaction, with k(cat)/K(M) values between 0.2 and 1.6 min(-1) microM(-1). Oxidation of 2 with an iron porphyrin-based chemical model of cytochrome P450 also led to a product derived from the oxidation of 2 at position 5. These results show that oxidation of diclofenac and its derivative 2, either with chemical model systems of cytochrome P450 or with recombinant human P450s, generally occurs at position 5. This position, para to the NH group on the more electron-rich aromatic ring of diclofenac derivatives, is thus, as expected, the privileged site of reaction of electrophilic, oxidant species. The most spectacular exception to this chemoselective 5-oxidation of diclofenac derivatives was found for oxidation of diclofenac itself with P450 2C9 (and P450 2C19 and 2C18 to a lesser extent), which only led to 4'-OHD. A likely explanation for this result is a strict positioning of diclofenac in the P450 2C9 active site, via its COO(-) function, to completely orientate its hydroxylation toward position 4', which is not chemically preferred. P450 2C19, 2C18, and 2C8 would not lead to such a strict positioning as they give mixtures of 4'-OHD and 5-OHD. The above results show that diclofenac derivatives are interesting tools to compare the active site topologies of human P450 2Cs.