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International audience; ObjectivesGiven the positive impact of appropriate medication management on graft outcome and therefore of patient survival and graft function, the pharmacist's role in the kidney transplantation team has evolved over recent decades. The primary objective of this study was to determine whether pharmacist-led intervention after kidney transplantation is associated with a lower graft rejection rate and intra-patient variation in tacrolimus trough concentrations (C-min). The study's secondary objective was to develop a questionnaire to identify patients at risk for highly variable C-min. MethodsWe retrospectively analysed kidney transplant recipients at Rennes University Hospital (France) between January 2013 and December 2020. Patients who received pharmacist-led education (intervention group, n=139) were compared with patients who did not (control group, n=131), according to graft survival at 1 year post-transplant, coefficient of variation (%CV) for the tacrolimus C-min, age, sex, length of hospital stay post-transplantation, body mass index, and Charlson Comorbidity Index. In the intervention group, a questionnaire assessing patient knowledge was introduced to compare scores with the %CV. ResultsIn the intervention group, 1 year post-transplant graft survival was higher (95.7% vs 88.5%, p=0.0289) and patients had fewer variabilities in C-min. The %CV was correlated with questionnaire scores (r=-0.9758, p

International audience

International audience; OBJECTIVES: Evaluate health literacy in transplant patients to better tailor the content of their continuing therapeutic education. METHODS: A 20-item questionnaire divided into five themes (sport/recreation, dietary measures, hygiene measures, recognition of the signs of graft rejection and medication management) was sent to transplant patient associations. Participants’ responses (a score out of 20 points), were analysed according to demographic characteristics, transplanted organ (kidney, liver or heart), type of donor (living or deceased), participation in a therapeutic patient education (TPE) programme, management of end-stage renal disease (with or without dialysis) and the date of transplant. RESULTS: 327 individuals completed the questionnaires (mean age 63.3±12.7 years, mean time post-transplant 13.1±12.1 years). From 2 years after transplantation, the patients’ score decreases significantly compared with the score obtained at hospital discharge. Patients who received TPE had significantly higher scores than patients who did not receive it, but only in the first 2 years post-transplant. The scores were different depending on the organs transplanted. Patients’ knowledge varied according to the theme; the percentage of errors being higher for questions related to hygienic and dietary rules. CONCLUSION: These findings highlight the importance of the role of the clinical pharmacist in maintaining the transplant recipient’s health literacy level over time to increase graft life. We show the topics on which pharmacists must acquire solid knowledge to best meet the needs of transplant patients.

Graphical abstract, As global vaccine production capacity is limited, every optimization strategy must be explored to rapidly increase the number of people vaccinated. The objective of this study is to determine which medical devices allow the extraction of the maximum number of doses from different vaccine vials (Pfizer-BioNTech, AstraZeneca, Moderna and Johnson & Johnson vaccines) by analyzing all the factors involved in the preparation of the injected doses. By measuring the dead-volume of 32 syringe-needle combinations, we show that fixed-needle syringe with a dead-volume of less than 5 µL can extract up to 7 doses from Pfizer vials, 13 doses from AstraZeneca vials, 12 doses from Moderna vials and 6 doses from Johnson & Johnson vials. We found that the syringe accuracy is important, and can compromise the chances of extracting additional doses when withdrawing too large a volume. For Pfizer vaccine, particular attention must be paid to the choice of dilution syringe, which may compromise the extraction of the 7th dose. The withdrawal of extra doses from vaccine vials was not operator-dependent. In this unprecedented health context, the medical device considerations presented here could help to optimize every COVID-19 vaccine vial.

International audience; There are few studies in humans dealing with the relationship between physico-chemical properties of drugs and their systemic bioavailability after administration via oral inhalation route (Fpulm). Getting further insight in the determinants of Fpulm after oral pulmonary inhalation could be of value for drugs considered for a systemic delivery as a result of poor oral bioavailability, as well as for drugs considered for a local delivery to anticipate their undesirable systemic effects. To better delineate the parameters influencing the systemic delivery after oral pulmonary inhalation in humans, we studied the influence of physico-chemical and permeability properties obtained in silico on the rate and extent of Fpulm in a series of 77 compounds with or without marketing approval for pulmonary delivery, and intended either for local or for systemic delivery. Principal component analysis (PCA) showed mainly that Fpulm was positively correlated with Papp and negatively correlated with %TPSA, without a significant influence of solubility and ionization fraction, and no apparent link with lipophilicity and drug size parameters. As a result of the small sample set, the performance of the different models as predictive of Fpulm were quite average with random forest algorithm displaying the best performance. As a whole, the different models captured between 50 to 60% of the variability with a prediction error of less than 20%. Tmax data suggested a significant positive influence of lipophilicity on absorption rate while charge apparently had no influence. A significant linear relationship between Cmax and dose (R(2) = "0.79) highlighted that Cmax was primarily dependent on dose and absorption rate and could be used to estimate Cmax in humans for new inhaled drugs.

International audience; The COVID-19 pandemic constitutes an unprecedented challenge to health care systems and societies worldwide. On 21 December 2020, the highly effective Pfizer–BioNTech COVID-19 vaccine was authorized in Europe, bringing big hopes for overcoming the pandemic.1 However, there are concerns about delayed availability of sufficient vaccine doses, forcing to prioritize target populations.2 Vaccination with the Pfizer–BioNTech COVID-19 vaccine consists of two doses (0.3 ml each) administered intramuscularly, 3 weeks apart. Each vial (2.25 ml theorical and 2.27 ml actual volume after dilution) meet the requirements of the European Pharmacopoeia allowing to obtain five doses using a syringe of a capacity not exceeding three times the volume to be measured and fitted with a 21-G needle not less than 2.5 cm in length.3 On 8 January 2021, European Medicines Agency announced that six doses could be extracted from a single vial using low dead-volume syringes and/or needles; i.e. no more than 35 μl for the syringe–needle combination.4 To date, no study has been carried out to propose recommendations on the use of adapted equipment. Here, we report the dead-volume of different syringe–needle combinations in order to inform such debate by relevant medical devices data.

International audience

International audience; In the context of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, hydroxychloroquine has been proposed as a potential agent to treat patients with COVID-19 (coronavirus disease 2019) caused by SARS-CoV-2 infection. Older adults are more susceptible to COVID-19 and some patients may require admission to the intensive care unit, where oral drug administration of solid forms may be compromised in many COVID-19 patients. However, a liquid formulation of hydroxychloroquine is not commercially available. This study describes how to prepare a 50 mg/mL hydroxychloroquine oral suspension using hydroxychloroquine sulfate powder and SyrSpend(Ⓡ) SF PH4 (dry) suspending vehicle. Moreover, a fully validated stability-indicating method has been developed to demonstrate the physicochemical stability of the compounded hydroxychloroquine oral suspension over 60 days under refrigeration (5 ± 3 °C). Finally, use of the proposed oral suspension provides a reliable solution to perform safe and accurate administration of hydroxychloroquine to patients with SARS-CoV-2 infection.

International audience; OBJECTIVES: Concurrent use of non-steroidal anti-inflammatory drugs (NSAIDs) with diuretics and renin-angiotensin-aldosterone system inhibitors (RAASI) has been associated with an increased risk of developing acute kidney injury (AKI) in the ambulatory setting. There is currently no information on AKI prevalence in hospitalised patients where initiation of NSAID prescription is quite frequent. The aim of our study was to assess the prevalence of AKI in patients treated with diuretics and/or RAASI in the hospital setting when NSAIDs are initiated. METHODS: This was a retrospective single centre study on inpatients receiving triple or dual association treatment. AKI was established according to evidence-based clinical practice guidelines in kidney disease (Kidney Disease Improving Global Outcome, KDIGO) using the following criteria : increase in serum creatinine (SCr) by ≥0.3 mg/dL (or ≥26.5 µmol/L) within 48 hours, or increase in SCr to ≥1.5 times baseline occurring within the last 7 days. RESULTS: AKI was identified in 5 of 151 patients (3.3%) treated with both diuretics and RAASI in whom NSAIDs were initiated, with a 49 µM average increase in SCr within 48 hours compared with baseline. AKI was identified in 2 of 117 (1.7%) patients treated with diuretics and NSAIDs, and in 1 of 427 (0.23%) patients treated with RAASI and NSAIDs. The average increase in SCr within 2 days was 29 µM. No AKI was identified in a control group of 1886 patients treated with diuretics and RAASI but with no initiation of NSAIDs during their hospitalisation. CONCLUSION: Initiation of NSAID therapy in hospitalised patients already being treated with diuretics and RAASI is a risk factor for AKI. The risk of AKI with the triple association appeared higher than with the dual association treatment.

Highlights • Hydroxychloroquine has been proposed as a potential agent to treat COVID-19 patients • Oral drug administration of solid forms may be comprised in many patients • Liquid formulation of hydroxychloroquine is not commercially available • Compounded hydroxychloroquine oral suspension is stable over 60 days, In the context of the SARS-CoV-2 pandemic, hydroxychloroquine has been proposed as a potential agent to treat COVID-19 patients. Older adults are more susceptible to COVID-19 and some patients may require admission in intensive care units, where oral drug administration of solid forms may be compromised in many COVID-19 patients. However, liquid formulation of hydroxychloroquine is not commercially available. This study describes how to prepare a 50 mg/mL hydroxychloroquine oral suspension using hydroxychloroquine sulfate powder and Syrspend SF dry pH4® suspending vehicle. Moreover, a fully validated stability indicating method has been developed to demonstrate the physicochemical stability of the compounded hydroxychloroquine oral suspension over 60 days under refrigeration (5 ± 3°C). Finally, use of the proposed oral suspension provides a reliable solution to perform safe and accurate administration of hydroxychloroquine to patients with SARS-CoV-2 infection.

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Backgrounds: Women are under-represented in senior academic and hospital positions in many countries. We aim to assess the place and the evolution of tenured female and male health practitioners’ working in French public Hospitals. Methods: Data of this observational study were collected from the National Management Centre (Centre National de Gestion) up to January 1, 2020. First, we describe demographic characteristics and specialties of all tenured medicine, pharmacy, and dentistry doctors’ working as Hospital Practitioners, Associate Professors, and Full Professors in French General and University-affiliated Hospitals in 2020. Then, we report the annual incidence of new entrance according to gender and professional status from 1999 to 2019. Findings: In 2020, 51 401 health practitioners (49·7% of female) are in activity in French public hospitals. Women represent 52·5% of the Hospital Practitioners, 48·6% of the Associate Professors, and 22·0% of the Full Professors. There are disparities between the rates of female Full Professors in medicine (20·6%), pharmacy (36·1%), and dentistry (44·3%). Women are nominated Hospital Practitioners earlier than men (37·1 versus 38·8 years), at a similar age among Associate Professors (36·1 versus 36·5 years), and at a later age among Full Professors (43·7 versus 41·9 years). Compared to men, the annual rates of appointed women varied between 1999 and 2019 from 47·6% to 60·4% for Hospital Practitioners, from 50·0% to 44·6% for Associate Professors, and from 11·2% to 33·3% for Full Professors. Interpretation: Although hospitals are becoming more and more feminised, there is still a gender gap to access the Full Professors status in medicine and pharmacy, but not in Dentistry. Despite a trend towards, gender equality has not yet been achieved regarding access to the highest positions. Funding Statement: None. Declaration of Interests: ALB, NA, CV, BH, FL, BL, MBM, AB, and JSA declare no competing interests.

BackgroundDexamethasone is commonly used to treat a wide variety of diseases including oncological disorders. The aim of this study was to propose a liquid formulation of dexamethasone. Therefore we have developed and assessed the stability of a 5 mg/mL dexamethasone oral suspension.MethodsA stability-indicating analytical method, using HPLC-UV, was developed and fully validated according to well-recognized international guidelines. The dexamethasone suspension was prepared using dexamethasone acetate powder and Ora-SweetResultsThe mean dexamethasone concentration of the compounded oral suspensions was equal to 5.07±0.17 mg/mL. No colour modifications, precipitate or suspending troubles was observed throughout the storage period and the pH of the oral suspensions was decreased slightly, from 4.41±0.01 to 4.20±0.02. According to the dexamethasone content determined by HPLC-UV, whatever storage condition was used, no significant degradation of dexamethasone occurred over the 60 days of the study period.ConclusionDexamethasone oral suspension prepared according to our conditions is stable over 60 days under regular storage temperatures (at 4±2 °C or at 21±3 °C).

Background Biotin at high dose (300 mg/d) is used in primary or secondary forms of multiple sclerosis (MS) (temporary use authorisation in France). Some biological tests are biased by this treatment, including immunoassays using biotin as a reagent. The results are likely to be overestimated for competitive assays (eg thyroid hormones) and underestimated for immunometric assays (eg thyroid-stimulating hormone). In 2007, the Agence Nationale de Securite du Medicamentdrew the attention of biologists and hospital directors. Pharmacists, despite their primary role in patient care, have been forgotten. Purpose This work presents the organisation established by the hospital pharmacy in collaboration with neurologists, biologists and the patients. Materials and methods Three types of actions have been established: Neurologists report to the pharmacist the initiation of treatment by biotin at high dose. Pharmacists update a shared file of patients with biologists. Biologists integrate this information into validation software in order to neutralise biotin in the serum before assaying. Outpatients are informed during the drug dispensation and receive a card entitled ‘patient treated with high dose biotin’ to present to all health professionals. All pharmacist who can deliver biotin have been trained. Results A series of 52 patients were monitored in our establishment on 1 October 2018. This initiative enabled us to sensitise the different stakeholders to this problem: retrospectively, disturbed thyroid hormone dosages results were found. The literature also cites false normal values of troponinaemia in the context of myocardial infarction and low-dose disturbances (15 mg/d). This collaborative work must enable the avoidance of this type of error. Conclusions The central role of hospital pharmacists at the interface between patients, prescribers and biologists has been essential in establishing a strategy to limit biological interference. The verbal exchange between the patient and medical team remains one of the best means of prevention. The regional association of MS patients has also been contacted to relay this entire device to other facilities. General practitioners and pharmacists should also be warned. This information relay reinforces the importance of reasoning on the entire ambulatory-hospital pathway, especially since an extension of the indications is envisaged. References and/or acknowledgements None

International audience; Purpose - Studies have documented potential drug-drug interactions (pDDIs) occurring in cancer patients mainly with solid malignancies, either in the ambulatory or hospital settings. While hematopoietic stem cell transplant (HSCT) patients during their bone marrow transplantation unit (BMTU) stay have rather complex medical regimens combining chemotherapy, anti-infectious agents, immunosuppressive agents, and supportive-care drugs, studies on potential DDIs are lacking. Our objective was to evaluate the prevalence and the density of pharmacokinetic and pharmacodynamic potential DDIs, and the evolution of the renal function in hematopoietic stem cell transplant (HSCT) adult recipients during their BMTU stay. Methods - Retrospective study in 31 adult patients consecutively admitted to the BMTU. Results - Prevalence of pharmacokinetic interactions was ten times lower than the pharmacodynamic interactions. The contraindications were rare, and only of pharmacokinetic origin. The main drugs involved in pharmacokinetic DDIs were ciclosporine, methotrexate, esomeprazole, tramadol, and vincristine. The median number of potential nephrotoxicity-related DDIs per patient was 7 and the median number of days during which nephrotoxicity-related DDIs potentially occurred was 77 days per patient. The decrease in glomerular filtration rate (GFR) throughout the BMTU stay (mean decrease of 13 ml/min) was correlated with the number of days of potential nephrotoxic drug interactions. Conclusions - Potential DDIs in HCST patients in BMTU were quite common. The DDIs from pharmacokinetic origin were less frequent, but of higher grade, than those of pharmacodynamic origin. The decrease in GFR suggests that the density of potential nephrotoxic drug interactions may be an issue to be considered in these patients.

International audience; Background - The hepatotoxicity of acetaminophen is recognised worldwide. Unfavourable prognoses relating to overdose include liver transplantation and/or death. Several hepatotoxicity risk factors (HRFs) should motivate the adjustment of acetaminophen daily intake (to 75 and low weight were associated with the prescriber's choice of dose. Neither chronic alcoholism nor hepatocellular insufficiency influenced the acetaminophen doses prescribed. Conclusion - Considering the widespread use of acetaminophen and its favourable safety profile compared with other analgesic drugs, it appears urgent to remind prescribers of the maximum daily dose recommendations for acetaminophen for patients with HRFs, especially those with chronic alcoholism and hepatocellular insufficiency.

Terbinafine is an antifungaldrug(inhibitor of ergosterol synthesis) known to induce skin reactions. A 58-year-old female was treated with terbinafine for onychomycosis. On the fifth day of treatment a skin rash emerged on her sun-exposed areas. Biological testing did not find any allergic signs. Other skin reactions are well known with terbinafine, but we depict here, a case of photosensitisation induced by treatment, generally unknown for this antifungal. This side effect can be prevented by medication reconciliation and pharmaceutical advice from the clinical pharmacist.

International audience; Cyclosporine is a widely used immunosuppressive agent to prevent rejection of solid organ transplant. Here, we describe the case of a 71-year-old man who received the prescribed dose of cyclosporine 10 times 6 days after a kidney transplantation because of a concentration miscalculation involving two galenic forms. The patient presented gastrointestinal and neurological disorders. Therapeutic drug monitoring revealed high cyclosporine blood concentrations (693 ng/mL, therapeutic range 100-300 ng/mL). Symptomatic management of digestive disorders was performed, and haemodialysis was started the day after the cyclosporine overdose in the face of acute renal failure. The patient’s disorders were quickly resolved. The dosing regimen was adapted in order to administer the most appropriate galenic form and to avoid another administration error. Long-term follow-up showed no failure of renal transplantation. The purpose of this case report is to warn physicians and clinical pharmacists about the vigilance required on cyclosporine prescription, especially when two galenic forms are administered to obtain the prescribed dose.

International audience; Diesel exhaust particles (DEPs) are common environmental air pollutants known to impair expression and activity of drug detoxifying proteins, including hepatic ATP-binding cassette (ABC) drug transporters. The present study was designed to determine whether organic DEP extract (DEPe) may also target ABC drug transporters in bronchial cells. DEPe (10 μg/mL) was demonstrated to induce mRNA and protein expression of the multidrug resistance-associated protein (MRP) 3 in cultured bronchial epithelial BEAS-2B cells, whereas mRNA levels of other MRPs, multidrug resistance gene 1 or breast cancer resistance protein were unchanged, reduced or not detected. DEPe also increased MRP3 mRNA expression in normal human bronchial epithelial cells. Inhibition of the aryl hydrocarbon receptor (AhR) pathway by AhR antagonist or AhR silencing, as well as the silencing of nuclear-factor-E2-related factor 2 (Nrf2) repressed DEPe-mediated MRP3 induction. This underlines the implication of the AhR and Nrf2 signaling cascades in DEPe-mediated MRP3 regulation. DEPe was additionally demonstrated to directly inhibit MRP activity in BEAS-2B cells, in a concentration-dependent manner. Taken together, these data indicate that DEPs may impair expression and activity of MRPs, notably MRP3, in human bronchial cells, which may have consequences in terms of lung barrier and toxicity for humans exposed to diesel pollution.

International audience; Introduction Drug transporters are now recognized as major actors of pharmacokinetics. They are also likely implicated in toxicokinetics and toxicology of environmental pollutants, notably pesticides, to which humans are widely exposed and which are known to exert various deleterious effects toward health. Interactions of pesticides with drug transporters are therefore important to consider.Areas covered This review provides an overview of the interactions of pesticides with membrane drug transporters, i.e. inhibition of their activity, regulation of their expression, and handling of pesticides. Consequences for toxicokinetics and toxicity of pesticides are additionally summarized and discussed.Expert opinion Some pesticides belonging to several chemical classes, such as organochlorine, pyrethroid, and organophosphorus pesticides, have been demonstrated to interact with various uptake and efflux drug transporters, including the efflux pump P-glycoprotein (P-gp) and the uptake organic cation transporters (OCTs). This provides proof of the concept that pesticide-transporter relationships merit attention. More extensive and systematic characterization of pesticide-transporter relationships, possibly through the use of in silico methods, is however likely required. In addition, consideration of transporter polymorphisms, pesticide mixture effects, and realistic pesticide concentrations reached in humans may help better define the in vivo relevance of pesticide-transporter interactions in terms of toxicokinetics and toxicity.

Resume Objectif Evaluer la performance des anti-TNFα dans le rhumatisme psoriasique (RP) dans des conditions de pratique courante. Methodes Nous avons inclus les patients atteints d’un RP chez qui un traitement par anti-TNFα avait ete initie entre avril 2001 et avril 2013 avec un suivi d’au moins 6 mois. Pour les formes peripheriques, le traitement a ete considere comme efficace chez les patients avec un avis d’experts favorable ou avec une amelioration clinique > 30 % du nombre d’articulations gonflees et douloureuses. Pour les formes axiales, les criteres d’efficacite etaient : l’amelioration du BASDAI d’au moins 2 points sur une echelle de 0 a 10 ou d’au moins 50 % (BASDAI50) ou sur une opinion d’expert. Le maintien therapeutique du premier anti-TNFα a ete calcule. Resultats L’etude avait inclus 193 patients (107/86 H/F, âge moyen 46,8 ans, duree moyenne d’evolution 6,7 ans, 171/22 de formes peripheriques/axiales). Seuls 48 (25 %) patients avaient recu un DMARD associe (65 % etaient sous methotrexate). La majorite des patients avaient recu comme premier anti-TNF l’etanercept (n = 102), suivi par l’adalimumab (n = 46), l’infliximab (n = 44) et le golimumab (n = 1). A 3 mois, 90 % des patients avaient obtenu une reponse adequate, 7 % avaient arrete le traitement du fait d’un manque d’efficacite et 3 % du fait d’effets secondaires. La duree mediane de maintien therapeutique etait de 2 ans. Le taux de maintien therapeutique a 1 et 2 ans etait respectivement de 77 % et de 67 %. Soixante-neuf (41 %) patients avaient change vers un deuxieme anti-TNFα et 29 vers un troisieme anti-TNF ; 82 % des switchers avaient repondu au traitement de seconde intention et 83 % avaient repondu au traitement de troisieme intention. Conclusion Un maintien therapeutique eleve et un taux de reponse tres eleve ont ete observes chez nos patients atteints de RP recevant un traitement par anti-TNFα en pratique courante.

Objective To evaluate the performance of anti-TNFα therapy in psoriatic arthritis (PsA) in a routine care setting. Methods Inclusion criteria were patients with PsA who initiated anti-TNFα therapy between April 2001 and April 2013 with a follow-up of at least 6 months. For peripheral forms, treatment was considered to be effective for patients with a favourable expert opinion or > 30% clinical improvement of swollen and tender joint counts. For axial forms, efficacy criteria were: improvement of BASDAI by at least 2 points on a scale from 0 to 10 or 50% improvement (BASDAI 50) or expert opinion. Drug survival of first anti-TNFα therapy was also investigated. Results The study included 193 patients (107/86 M/F, mean age: 46.8 years, mean disease duration: 6.7 years, 171/22 peripheral/axial forms). Only 48 (25%) patients received concomitant DMARD therapy (65% were treated with methotrexate). The majority of patients started with first-line etanercept ( n = 102), followed by adalimumab ( n = 46), infliximab ( n = 44) and golimumab ( n = 1). At 3 months, 90% of patients had obtained an adequate response, 7% had discontinued due to lack of efficacy and 3% due to adverse events. Median drug survival was 2 years. One-year and 2-year drug survival rates were 77% and 67%, respectively. Seventy-nine (41%) patients switched to a second anti-TNFα and 29 to a third anti-TNFα; 82% of switchers responded to second-line therapy and 83% responded to third-line therapy. Conclusion High drug survival and high response rates were observed in these patients with PsA receiving their first anti-TNFα therapy in routine clinical practice.

Bisphenol A (BPA) is an endocrine disruptor found in food containers and plastic beverages and also in medical devices such as dialyzers. The aim of this study is while taking into account the BPA originating in medical devices and the water used in dialysate production, to provide the first published investigation of overall potential exposure to BPA during hemodialysis treatment in patients suffering from end-stage renal disease. BPA concentration in water (at each step of purification treatment) and in dialysate and BPA leaching from dialyzers were determined using solid-phase extraction coupled to ultra-high-performance-liquid chromatography tandem mass spectrometry. We have corroborated the hypothesis that a significant amount of BPA may migrate from dialyzers and also demonstrated that BPA is provided by the water used in dialysate production (8.0±5.2ngL(-1) on average) and by dialysis machine and dialysate cartridges, leading to dialysate contamination of 22.7±15.6ngL(-1) on average. Taking into account all the sources of BPA contamination that may come into play during a hemodialysis session, the highest exposure could reach an estimated 140ng/kg b.w./day for hemodialyzed patients, directly available for systemic exposure. Finally, BPA contamination should be taken into account as concerns both the medical devices commonly used in hemodialysis and purified water production systems.

International audience; Bisphenol A (BPA) is a well-known endocrine disruptor. Chlorinated derivatives of BPA (ClxBPA) may be formed by reaction of chlorine with BPA present in drinking water. ClxBPA exhibit a higher level of estrogenic activity than BPA. While many studies have reported detectable BPA concentrations in urine, only very few studies were conducted in regards to ClxBPA. Since ClxBPA are potentially more toxic, it is important to assess large-scale exposure of the general population. Indeed, in the field of environment health, large studies are required to assess exposure to pollutants at ultratrace concentrations; therefore, analytical methods have to be rapid and sensitive. This work intends to validate a highly sensitive and rapid analytical method suitable to evaluate BPA and ClxBPA exposures during large-scale biomonitoring studies. For that purpose, a method based on online solid-phase extraction coupled with isotope dilution ultrahigh - performance liquid chromatography-tandem mass spectrometry was developed and validated according to accepted guidelines. The matrix-matched calibration curve ranged from 0.25 to 16.0 ng mL¹ and from 0.025 to 1.60 ng mL¹ for BPA and ClxBPA, respectively. This method was precise (the intra- and inter-day coefficients of variation of quality control were

Objective.While remission is possible in patients with ankylosing spondylitis (AS), it is often unclear what attitude should be adopted once remission has occurred. We investigated whether dosage adjustment is an effective means of maintaining remission.Methods.This was a retrospective study drawn from clinical situations. Remission was defined using clinical measures [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≤ 20/100 and no peripheral joint disease] and biological measures [C-reactive protein (CRP) levels ≤ normal value]. The tumor necrosis factor-α (TNF-α) inhibitors used were infliximab, adalimumab, and etanercept. Response predictors of remission were evaluated by logistic regression (age, CRP, HLA-B27 positivity, sex, duration of disease, and anti-TNF-α naivety). CRP and BASDAI were evaluated before and after dosage adjustment at about 6, 12, 24, and 36 months.Results.One hundred eighty-nine patients with AS were included in the study, with a mean followup of 43.5 (± 17.9) months after the introduction of the first anti-TNF-α inhibitor. Mean age was 45.6 (± 12.5) years. Remission had occurred in 65 patients (35%). Significant response predictors of remission were male sex (p = 0.003) and anti-TNF-α naivety (p < 0.001). Dosage adjustment was observed 49 times, and progressively reducing treatment frequency was effective to maintain remission in a large number of patients for 36 months. The cumulative probability of continuing anti-TNF-α after dosage adjustment was 79.0% at 12 months, 70.5% at 24 months, and 58.8% at 36 months.Conclusion.Remission had occurred in 35% of the patients with AS under anti-TNF-α inhibitor therapy. Dosage adjustment and progressively reducing treatment frequency was effective in maintaining remission.