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Notre établissement a souhaité généraliser une activité de conciliation médicamenteuse (CM) d’entrée basée sur deux modes d’admission et sur une grille de priorisation des patients afin de rationaliser les ressources pharmaceutiques.

L’identification des patients, des prescriptions et situations à risque iatrogène est un enjeu majeur de l’optimisation de la prise en charge médicamenteuse et de la lutte contre l’iatrogénie. L’objectif de cette étude est de mettre en pratique l’utilisation de différents facteurs de risque récemment publiés dans l’étude de Leroy et al. afin de détecter les situations à risque.

The accuracy of global water balance estimates is limited by the lack of observations at large scale and the uncertainties of model simulations. Global retrievals of terrestrial water storage (TWS) change and soil moisture (SM) from satellites provide an opportunity to improve model estimates through data assimilation. However, combining these two data sets is challenging due to the disparity in temporal and spatial resolution at both vertical and horizontal scale. For the first time, TWS observations from the Gravity Recovery and Climate Experiment (GRACE) and near‐surface SM observations from the Soil Moisture and Ocean Salinity (SMOS) were jointly assimilated into a water balance model using the Ensemble Kalman Smoother from January 2010 to December 2013 for the Australian continent. The performance of joint assimilation was assessed against open‐loop model simulations and the assimilation of either GRACE TWS anomalies or SMOS SM alone. The SMOS‐only assimilation improved SM estimates but reduced the accuracy of groundwater and TWS estimates. The GRACE‐only assimilation improved groundwater estimates but did not always produce accurate estimates of SM. The joint assimilation typically led to more accurate water storage profile estimates with improved surface SM, root‐zone SM, and groundwater estimates against in situ observations. The assimilation successfully downscaled GRACE‐derived integrated water storage horizontally and vertically into individual water stores at the same spatial scale as the model and SMOS, and partitioned monthly averaged TWS into daily estimates. These results demonstrate that satellite TWS and SM measurements can be jointly assimilated to produce improved water balance component estimates. GRACE TWS and SMOS SM observations were jointly assimilated for the first timeJoint assimilation improved water balance component estimates, especially in SM profile and groundwaterJoint assimilation performs better than assimilation of GRACE or SMOS only

The action of a hospital pharmacist can improve drug management and should focus on high risk drugs, services or patients. The aim of this study was to identify risk factors in medical files and thus identify patients with high iatrogenic risks.

Les actions du pharmacien hospitalier pour améliorer la prise en charge médicamenteuse doivent s’orienter sur les patients, services ou médicaments à risque. L’objectif de cette étude est d’identifier des facteurs de risque dans les dossiers et ainsi repérer des patients à risque iatrogène élevé.

Global Positioning System (GPS) deformation measurements were combined with groundwater level data to examine the spatiotemporal variability of groundwater storage in the Lachlan catchment located in central New South Wales (Australia). After correcting for effects of glacial isostatic adjustment, non‐tidal oceanic and atmospheric loading as well as hydrologic loading using existing models, we show that the seasonal and interannual variability of ground deformation and hydraulic head level data, extracted using wavelet time‐frequency analysis, exhibits an in‐phase behavior, indicating that the observed surface deformation is the poroelastic response to groundwater pressure change in aquifer system. Combination of GPS displacement and groundwater level change enables the estimation of elastic skeletal specific storage coefficients, which were then used for estimating groundwater storage changes. The estimated groundwater storage changes clearly reflect the four climate events of the Lachlan catchment since 1996: (a) the Millennium drought over 1996–2009, (b) the 2011–2012 La Nina and two significant floods in 2012 and 2016, (c) the drought conditions from mid‐2017 to late‐2019, and (d) the return of La Nina conditions since early 2020. We also found annual and long‐term groundwater storage variations of respectively ∼25±2.7GL$\sim 25\,\pm \,2.7\,\mathrm{G}\mathrm{L}$and ∼−5±0.57GL/yr$\sim -5\,\pm \,0.57\,\mathrm{G}\mathrm{L}/\mathrm{y}\mathrm{r}$over the period 2012–2021. Moreover, we show that groundwater level fluctuations can be predicted from GPS displacement measurements and storage coefficients with sufficient accuracy (80% correlation and 70% RMS reduction when compared in terms of seasonal cycle). This study provides essential information that can contribute to future groundwater planning, management, and control over the Australian continent. Groundwater extraction or recharge changes the height of the Earth's surface, which can be obtained from displacement measurements derived from Global Positioning System (GPS). We combined the GPS displacement measurements over the Lachlan aquifer, located in central New South Wales (Australia), with the groundwater level change to study groundwater storage variation. The estimated groundwater storage changes reflect the major climate conditions over the area since 1996 such as the Millennium drought and the significant La Nina events in 2011 and 2020. We further analyze the aquifer response to the rainfall and found a delay ranging from 3 weeks to 2 months between the rainfall and groundwater wells levels, depending on the depth of the aquifer. We estimate groundwater storage variation by combining Global Positioning System (GPS) vertical displacement and groundwater level dataInterannual variability measured by GPS vertical deformation is mainly driven by poroelasticity effect due to groundwater storage changesThe method is able to model seasonal groundwater level fluctuation using GPS displacement measurement and storage coefficient of the aquifer We estimate groundwater storage variation by combining Global Positioning System (GPS) vertical displacement and groundwater level data Interannual variability measured by GPS vertical deformation is mainly driven by poroelasticity effect due to groundwater storage changes The method is able to model seasonal groundwater level fluctuation using GPS displacement measurement and storage coefficient of the aquifer

La ciclosporine 0,1 % collyre (Cs 0,1 %) est indiquée dans la kératite sévère résistante aux substituts lacrymaux. Ce médicament est commercialisé, en France, depuis décembre 2013, d’abord sous le statut d’autorisation temporaire d’utilisation puis en accès précoce. Suite à la publication au Journal Officielen juillet 2021 de la fin de prise en charge en accès précoce, il a été déremboursé à partir du 1ernovembre 2021 compte tenu de l’absence d’efficacité démontrée dans les études cliniques. Il reste néanmoins disponible en rétrocession à la charge du patient jusqu’en juillet 2022.

Background:Few data exist on the prevalence of female sexual dysfunction (FSD) in thyroid disorders. Aim:We evaluated FSD in women with thyroid diseases and in control age-matched healthy women to investigate the relationship between sexual function and thyroid hormones. Methods:One hundred and four women with thyroid diseases and 53 controls participated in the study. Eighteen with hyperthyroidism (Group 1), 22 hypothyroidism (Group 2), 45 Hashimoto’s thyroiditis (Group 3), 19 nodular goiter (Group 4) underwent thyroid function evaluation and sonography. The Female Sexual Function Index (FSFI) assessed sexual function. Results:The prevalence of FSD was 46.1% in thyroid diseases and 20.7% in controls. Only in Group 4, the prevalence (68.4%) was significantly higher than in controls (p<0.005). The mean total FSFI score was 20.1±7.1 in women with thyroid diseases and 25.6±4.7 in the controls (p<0.001). Compared with controls, there was a significant decrease of desire in Group 2; desire, arousal and lubrication in Group 3; desire, arousal, lubrication, orgasm and satisfaction in Group 4. In thyroid diseases the prevalence of FSD was 53% and 42%, while in the controls was 55% and 20%, in menopausal and pre-menopausal groups, respectively. We found a significant inverse correlation between TSH and FSFI (r=−0.7, p=0.01) in Group 4, which showed the lowest FSFI score (17.8±5.7) and the highest body mass index (28.4±7.1 kg/m2). Conclusions:Women with thyroid diseases present a higher prevalence of FSD than controls. Although our findings suggest a higher impairment of sexual function in Group 4 and a role for TSH in FSD, further researches are needed.

Type IIIb polyglandular autoimmune disease comprises autoimmune thyroid disease (HT) and chronic atrophic gastritis (AIG). Hypergastrinemia, secondary to AIG, predisposes to gastric enterochromaffin-like cell (ECL) hyperplasia, a preneoplastic condition. We evaluated the prevalence of AIG, hypergastrinemia and ECL hyperplasia in HT patients. A secondary end-point was to assess the efficacy of treatment with a somatostatin analogue in HT patient with ECL hyperplasia. From 2009 to 2011, 146 HT patients were enrolled in a prospective study. All cases underwent hormonal profile, and parietal cell antibody (PCA), gastrin, and chromogranin A (CgA) serum level assays. Selected patients with elevated gastrin and CgA levels underwent gastro esophageal endoscopy (EGDS). Patients positive for ECL hyperplasia received Octreotide LAR 30 mg/28 days for 12 months. Gastrin and CgA assays were repeated every three months and EGDS after one year. The results show that gastrin and CgA were significantly higher than normal in 17/115 (14.7%) patients. Seven more HT had isolated PCA positivity and in the 17 PCA positive patients histology diagnosed AIG, corpus prevalent, with mild to moderate atrophy. Diffuse ECL hyperplasia of the gastric body was present in three subjects, one of them presenting a type-1 carcinoid. Gastrin and CgA levels were significantly reduced (p<0.01) after 3 months of therapy with a somatostatin analogue and returned to normal after 1 year. ECL hyperplasia regressed in all three patients. We suggest that selected HT patients may need a more accurate surveillance for early signs of gastric EC risk. In the case of altered values of gastrin and in the presence of PCA positivity, EGDS and histology should be performed for an early diagnosis of AIG and treatment of ECL hyperplasia.

Background:Pubertal gynecomastia is a common problem occurring in up to 65% of adolescent boys. Gynecomastia comes at a time when self-image awareness is at its greatest and psychologically could be a psychologically disabling condition. Surgery is considered the mainstay of treatment for severe or persistent cases. A medical management aimed at altering the effective androgen/estrogen ratio has been suggested with inconstant results. Some promising results have been obtained by using anti-estrogens. Surprisingly there are no data on the estrogen receptor (ER) α and β RNA expression in gynecomastia. Aim:We studied ER RNA subtypes in pubertal gynecomastia. Methods:ERα and β RNA were determined by real time RT-PCR in 50 mammary samples from pubertal boys with idiopathic gynecomastia subjected to reductive mammoplasty. To study ERα and β pattern of expression, epithelial and stromal primary cell cultures were set up from fresh tissues. Results:These analyses indicated that in all stromal cells ERβ was expressed at higher level than ERα and in epithelial cells both ERα and ERβ were barely detectable. Conclusions:Our data suggest that also stromal cells are involved in the pathophysiology of pubertal gynecomastia. The high level of expression of ERβ seen in pubertal gynecomastia adds new insight on validation of ERβ as a target for candidate diseases and exploration of ERβ as a marker for clinical decision-making and treatment in pubertal gynecomastia. This could drive to search for new and selective anti-estrogen drugs for medical treatment of pubertal gynecomastia with a particular attention to the ERβ-selective ligand.

Accurate initial conditions play a critical role in improving predictive accuracy of hydrological models for quantities such as streamflow generation. Streamflow observations from in situ gauging sites have been assimilated in a wide range of past research to improve lumped catchment streamflow. However, spatio‐temporal state updating in distributed hydrological models through streamflow data assimilation (DA) remains a challenge due to the large dimensional disparity between model state space and observation space. This study explores the use of model spatio‐temporal variance‐covariance from simulated climatology as a surrogate for model error, as a way of distributing constraint from gauge measurements spatially. In the approach developed here, grid cells within and surrounding gauged catchments were updated simultaneously. The proposed DA method leads to a substantial improvement in performance and reliability compared to open‐loop (OL) estimates of streamflow. In particular, for “ungauged” catchments updated using streamflow observations from neighboring catchments, the mean absolute error (MAE) was reduced by 20% on average after the assimilation. In addition, improvements from using the analyzed states as initial conditions were found to persist for more than 1 week, and even longer for catchments with high annual runoff. The improvement in streamflow forecasts using initial conditions from DA can be more than 40% in terms of MAE compared to OL results for 1 day lead time, and more than 10% for 5 days lead time. Streamflow is one of the most important predicted quantities in operational hydrological forecasting and water resource management. Producing credible predictions of the spatial and temporal patterns of streamflow remains challenging due to the absence of direct measurements to aid in calibrating models for parts of the modeling domain. This study explored a model‐data integration approach to spread constraint from streamflow observations to grid cells within catchments and potentially surrounding ungauged catchments in space and time. We found that the proposed approach can improve streamflow estimates in ungauged catchments and the improvement can persist for more than a week and even longer for catchments with high mean annual runoff. This approach demonstrates the potential to improve streamflow simulation and flood forecasting for both gauged and ungauged catchments. Spatio‐temporal model variance‐covariance are proposed as surrogates for model error estimates to assimilate streamflow observations into a distributed water balance modelStreamflow data assimilation improves streamflow forecast for more than 7 days due to analyzed initial conditionThe proposed method can be used to improve streamflow simulations in ungauged catchments using observations from neighboring catchments Spatio‐temporal model variance‐covariance are proposed as surrogates for model error estimates to assimilate streamflow observations into a distributed water balance model Streamflow data assimilation improves streamflow forecast for more than 7 days due to analyzed initial condition The proposed method can be used to improve streamflow simulations in ungauged catchments using observations from neighboring catchments

To characterize HIV-1 genotypes in candidate populations for a prime-boost phase III vaccine trial in Thailand, specimens from prevalent and incident HIV-1 infections from a family planning clinic population in Rayong Province and a community cohort in Chon Buri Province, collected from 1998 to 2001, were genotyped. A new multiregion hybridization assay, MHAbce, capable of distinguishing HIV-1 CRF01–AE, subtype B, and subtype C and their recombinants, was developed and applied to prevalent infections. Most incident and selected prevalent infections were studied by complete genome sequencing. By MHAbce, 168 of 194 prevalent infections were genotyped. Of these, 90.5% were CRF01–AE, 2.4% were subtype B, and 7.2% showed discordant or dual probe reactivity, indicative of recombination or dual infection, respectively. Among 23 incident infections, 20 were sequenced. Eighteen CRF01–AE, one subtype B, and one CRF01/B recombinant strains were seen. Two CRF01/B and one CRF01/C recombinant were identified among selected prevalent infections. These results indicate that incident and prevalent HIV-1 infections in Rayong and Chon Buri during 1998–2001 were 90% CRF01–AE, 3% subtype B, and 7% either recombinant or dual. This study frames the genetic diversity of HIV-1 in these cohorts in their preparatory phase for the ongoing ALVACHIV (vCP1521) prime, AIDSVAX B/E boost, phase III vaccine trial and will provide a benchmark for interpretation and analysis.

Grape phylloxera (Daktulosphaira vitifoliae Fitch) is a root-feeding pest of grapevines. In Australia, phylloxera-infested vineyards are subjected to quarantine restrictions and early detection remains vital for the timely implementation of post-outbreak quarantine protocols. Current detection methods rely on time-consuming ground surveying, which involves detailed examination of grapevine (Vitis vinifera L.) root systems. Leaf pigment composition is often a sensitive indicator of plant stress. The increasing popularity of remote sensing systems, which exploit those changes in pigments observed with plant stress, offers a real possibility for the development of a phylloxera-specific remote detection system. Our objective was to investigate changes in grapevine leaf pigments associated with phylloxera infestation and to relate any changes to appropriate reflectance indices. This was achieved with a glasshouse experiment in which the responses of two vine cultivars (Cabernet Sauvignon and Shiraz) to phylloxera infestation were compared with their responses to water and nitrogen deficiencies. The responses of leaf pigments to phylloxera infestation were also investigated in Pinot Noir and Cabernet Sauvignon grapevines grown under field conditions. A reduction in the leaf chlorophyll content and an increase in photoprotective pigment concentrations were observed in leaves of phylloxera-infested grapevines compared with uninfested vines. The photochemical reflectance index (PRI) was found to be most closely associated with the ratio of total carotenoid to chlorophyll in these vines.

HIV-1 subtype B and CRF01_AE have been in circulation in Thailand and Southeast Asia for more than a decade. Initially separated by risk group, the two strains are increasingly intermixed, and two recombinant strains of essentially reciprocal structure have been recently reported. Here we identify additional CRF_01B recombinants and provide the evidence that HIV-1 strains now pass freely between the two high-risk populations. HIV isolates that showed discordance between CRF01_AE and subtype B in multi-region genotyping assays were selected for the study. They were drawn from 3 different cohorts in Thailand representing different risk behaviors and demographic characteristics: a drug user cohort in the north, a family planning clinic attendee cohort in the southeast, and a cohort study of the mucosal virology and immunology of HIV-1 infection in Thailand. The DNA from these isolates was PCR amplified to recover the full HIV-1 genome and subjected to sequencing and phylogenetic analysis. We establish that one particular CRF_01B recombinant, with the external envelope of subtype B and the rest of the genome from CRF01_AE, is circulating widely in Thailand. Termed CRF15_01B (also referred to as CRF15), the strain was primarily heterosexually transmitted, although injecting drug use (IDU) also played a role. In aggregate data from the studies, CRF15 constituted 1.7% of all HIV-1 infections (95% confidence interval 0.5-4.4%) and was dispersed widely in the country. The previously separate heterosexual and IDU epidemics have apparently been bridged by a new CRF. The entry of CRF15 into the mainstream of the epidemic signals new complexity in the long stable molecular picture in Thailand. These recombinants must be considered in ongoing or projected efficacy evaluations of HIV-1 vaccines and antiviral therapies.

Human immunodeficiency virus type 1 (HIV) RNA load was measured in paired samples of peripheral blood plasma and nasopharyngeal (NP) washes from 97 Thai subjects infected with subtype E or B. HIV RNA was quantifiable in 93% of peripheral blood plasma samples tested and was inversely correlated (ρ =-0.524; p < 0.001) with CD4 absolute count. HIV RNA was quantifiable in 29% of NP samples tested, and the median value was less than that of plasma viral load. HIV RNA load in NP samples was correlated (ρ = 0.388; p < 0.001) with viral load in peripheral blood. HIV RNA was not detected in NP washes from subjects with undetectable plasma viral load. Virus isolation attempts on two NP samples were negative. The results do not support local HIV production in the nasopharynx, but extend current knowledge of HIV shedding to include the NP compartment.

Background:A rare complication of Chronic Lymphocytic Leukemia (CLL), Richter's Syndrome (RS) represents the transformation of a pre-existing CLL into a Diffuse Large B-cell Lymphoma (DLBCL), generally associated with poor prognosis. Current therapeutic approaches are limited and do not significantly reduce disease progression. For these reasons there is intense investigation to identify potentially druggable molecular circuits, opening the way to innovative combination therapies.

Deaglio: Heidelberg Pharma: Research Funding; Astra Zeneca: Research Funding.

A cohort of Royal Thai Army (RTA) conscripts was followed in civilian life after completing 2 years of military service, to determine whether such a cohort might be suitable for HIV vaccine trials. Objectives were to identify correlates of participation and to determine the occurrence of risk behaviors for HIV infection after discharge from the military. The cohort was selected from among conscripts who had participated in HIV studies from 1991 to 1993. Risk factors were surveyed at 3, 9, and 15 months after discharge (1993–1995). Change in risk was evaluated based on deviations from expected distributions of risk categories for sentinel behaviors, assessed with chi-square analysis. HIV seroconversion rates (SR) and 95% confidence intervals (CI) were calculated. A total of 380 men returned after discharge. Seven men seroconverted after discharge; the SR (95% CI) was 2.02/100 person-years (0.81–4.17). Among changes in risk were reduced visits to commercial sex workers (CSWs), more condom use with CSWs, and less alcohol use prior to CSW visits. Behaviors associated with increased risk of HIV seroconversion declined after military service. Thus, sufficient numbers of outcome events for vaccine trials may not be attained with this type of cohort. Nonetheless, these findings provide data on the dynamics of the HIV epidemic in Thailand and the development of HIV vaccine cohorts.

Water penetration across brick masonry exterior walls is a prob lem that building owners and construction professionals must deal with fre quently. Water repellents are often used in an attempt to resolve water penetration problems in certain remedial applications. Unfortunately, the information avail able to building owners and construction professionals regarding the use and evaluation of water repellents is limited. Little practical information exists to assist in the selection of such products and in the evaluation of their performance and durability. As part of a CMHC research project, Patenaude-Chiovitti Inc. carried out an evaluation of such products, exposing problems of performance evaluation of water repellents for above grade masonry. Six series oftests were conducted us ing a modified ASTM E-514 procedure and water uptake tube methods to evalu ate the performance of five commercially available masonry water repellents. The results of the study have indicated substantial improvements in the resistance to water penetration upon application of these products to clay brick wall assemblies. The data accumulated during this study may have also revealed a trend indicating an increase in the rate of water penetration from the time of product application (i.e., reduced repellency), necessitating product reapplication after a given time interval. Readers are cautioned in the interpretation of the test data without addi tional information pertaining to the vapour diffusion characteristics of the ap plied products and durability concerns.

AbstractDuring the 1984–1985 influenza season, outbreaks of influenza A (H3N2) occurred in three Connecticut nursing homes. Influenza vaccination rates were 67% (96 out of 144), 35% (30 out of 85) and 69% (332 out of 483), respectively. The relative risk of illness for vaccinated compared to unvaccinated residents was 1.8 (95% confidence interval, 0.6, 5.9), 1.6 (95% confidence interval, 0.8, 3.0) and 1.1 (95% confidence interval, 0.8, 1.7) for each of the three nursing homes, respectively. In the third outbreak, 22 vaccinated residents without clinical illness had a geometric mean titer of hemagglutination-inhibition (HI) antibody of 20. Although low, this titer was significantly higher than that of nine unvaccinated residents without clinical illness (12, p<.05); only three (14%) vaccinated residents had HI titers of 340. These results suggest that levels of HI antibody in vaccinated residents were not protective at the time of the third outbreak, four to five months after vaccination. In general, the study of vaccine effectiveness in nursing homes is limited by sample size and statistical power. Despite these limits, the retrospective investigation of influenza outbreaks in nursing homes is often the only practical way to evaluate influenza vaccine effectiveness in the elderly on a yearly basis.

Summary: The aim of the present work has been the determination of the effectiveness of a primary prevention in the allergopathy induced by house dust mites weighing its benefits as regards asthmatic symptomatology.A sample of 56 subjects, aged 6 to 30 years, monosensitive to house dust mites (DTP and DTF) and with a diagnosis of bronchial asthma has been examined. The patients have entered a study plan whose purpose has been the evaluation of the effects of an environmental improvement on symptomatology. The diagnosis of asthma induced by house dust mites has been confirmed both by in vivo (Prick-test) and in vitro (PRIST and RAST) investigations.A follow-up after 3 months has shown that the hygienic measures have produced beneficial effects on symptomatology in as many as 22 patients (52.4%) out of a total of 42 who have put into practice the environmental improvement. These results encourage to proceed on this path in the choice of the therapy for those subjects affected by respiratory allergopathy to house dust mites.

•Stomoxys calcitrans(stable fly) is a potential mechanical vector for the lumpy skin disease virus.•Lumpy skin disease virus could be isolated from regurgitated blood and faeces of stable flies exposed to virus-spiked blood.•Lumpy skin disease virus could survive in the stable flies’ abdomens up to two days without losing its infectivity.•Stomoxys calcitranswas present in cattle farms also at higher altitudes (2128 m asl) in Switzerland.

ABSTRACTWe report a prospective comparison of human immunodeficiency virus type 1 testing by enzyme immunoassay and Western blot with four rapid tests of 486 subjects performed in rural Kenya. Rapid test sensitivity was 100%. Specificity ranged from 99.1 to 100%. Combined use of two Food and Drug Administration-approved rapid tests yielded a single false-positive result.

BackgroundMedication reconciliation (MR) makes it possible to identify medication errors. Because it is labour-intensive, it is often limited to certain specific hospital units (HU).PurposeThe goal of this study was to evaluate a MR activity targeting patients at the highest risk admitted to the emergency unit.Material and methodsA single-centre prospective study was performed for 6 months in patients hospitalised through the emergency unit. Emergency unit physicians or nurses would fill in a prioritisation grid of MR including 10 clinical and therapeutic factors. This grid, which was based on a bibliographic study and a prior internal study, included a box « don’t know » (DK) for every factor. A pharmacist collected the grids daily and calculated the risk score of each patient: in the case of a score ≥10, a pharmacist performed a MR of the patient in the unit where s/he was hospitalised.ResultsA prioritisation grid was filled out for 583 patients. Ten and 36% of the grids included at least one DK box checked by the physicians and the nurses, respectively. Twenty-four per cent of the patients were eligible for MR according to the physicians, 11% according to the nurses, for a total of 130 patients. Fifty-six MR were performed in 15 different HU, which represented 43% of the identified patients, with an average of 1 hour per MR of the pharmacist’s time. The number of unintended medication discrepancies (UMD) was 1.2/patient.ConclusionThis grid seems to be adapted to the prioritisation of MR, because 24% and 11% of the patients had a score ≥10. It identified the need for MR in a large number of HU, which is the originality of our MR activity. All the priority MR could not be performed because of early release/death of patients or lack of time. The low rate of patients at risk and the high rate of DK checked by nurses suggests that nurses under-evaluate this risk. Physicians seem to have a better understanding of the patients and treatment. The MR of patients at risk made it possible to identify a number of UMD similar to that found in other French studies.No conflict of interest

Face aux difficultés d’approvisionnement en produits de santé, l’ANSM recense sur son site Internet les difficultés d’approvisionnement à partir des signalements des firmes pharmaceutiques. Les difficultés d’approvisionnement en médicaments ont un impact sur l’activité de la PUI, la prise en charge optimale des patients et un risque d’interruption d’un traitement ou un retard à l’initiation de traitement. Évaluer l’impact des difficultés d’approvisionnement sur les activités de notre PUI. Un suivi prospectif des difficultés d’approvisionnement en médicaments a été effectué entre février 2015 et février 2016. La consultation des courriers des fournisseurs et le site Internet de l’ANSM ont permis une analyse des causes de ruptures. Enfin, l’impact sur l’activité de la PUI a été évalué sur la gestion des commandes et l’activité de rétrocession. Au total, 80 médicaments ont connu une difficulté d’approvisionnement dont 55 médicaments en rupture totale et 25 médicaments contingentés. Dix pour cent (8) des médicaments ont fait l’objet d’une importation temporaire pour pallier la rupture. Pour 7,5 % (6) des produits, il y a eu au moins 2 périodes de rupture. Quarante-neuf pour cent (39) des médicaments ont fait l’objet d’un signalement sur l’ANSM. Les difficultés ont concerné 15 classes pharmacothérapeutiques. La durée moyenne de rupture était de 153jours (10 ;365). Les causes de rupture étaient des difficultés de production dans 57,5 % des cas et inconnues dans 30 %. Trois médicaments ont eu un arrêt de commercialisation et une proposition de substitution par des médicaments importés. Au total, 680 actes de rétrocession de 4 médicaments ont été effectués suite à leur rupture en ville pour 188 patients externes sur les 762 patients de notre file active (24,7 %). Cela a conduit à effectuer 48 commandes de médicaments soit une augmentation de 15 % des commandes de médicaments rétrocédés. Quize procédures d’achat pour compte ont été effectuées suite à des ruptures dans le cadre des marchés. Les procédures de contingentements mis en place par les fournisseurs compliquent l’approvisionnement en allongeant les délais de livraison. Les ruptures d’approvisionnement posent des difficultés au pharmacien pour assurer la continuité des traitements des patients et entraînent une surcharge de travail. Pour le patient, cela peut nécessiter un déplacement à l’hôpital le plus proche autorisé à effectuer de la rétrocession. Ces difficultés ont été prises en compte par les autorités de santé. Un projet de loi (no 2016-41 du 26 janvier 2016) prévoit de pallier, en partie, ces pénuries en instaurant une liste de médicaments d’intérêt thérapeutique majeur, qui devront faire l’objet d’un plan de gestion des pénuries de la part des industriels.

Le conseil aux patients au moment de la dispensation est une étape importante de la rétrocession hospitalière car il favorise le bon usage des médicaments en ambulatoire. Il est primordial de former les acteurs de la rétrocession pour délivrer aux patients une information de qualité. L’objectif de cette étude est d’évaluer l’efficacité d’une formation présentielle à destination des préparateurs portant sur un médicament régulièrement rétrocédé.

Despite frequent anemia and multiple transfusions during AML chemotherapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT), recommendations and marketing authorization for erythropoietin (EPO) use are still missing. In the current prospective study, as primary objective, we evaluated the effect of EPO on patient's quality of life (QOL). Secondary objective was hemoglobin (Hb) recovery. In addition, a paired matched analysis using similar population was conducted to compare platelets (Pt) and red blood cells (RBC) transfusion number.We included adult patients with Hb level ≤11g/dl induced by 1, 2 or 3 consolidation chemotherapy for AML in complete remission (CR) (group 1); or by allo-HSCT for any hematological disease (group 2). EPO was administered Sc. once per week during a maximum period of 6 months: for group 1, ARANESP® 150μg; for group 2, NEORECORMON® 30000IU; Hb level was monitored every week. Injections were stopped once the Hb level reached 12g/dl without any transfusion. If after 4 injections, no improvement was observed, doses were doubled, and if after 8 injections, no improvement was observed, patient was taken off-study for EPO inefficiency. The QOL was measured at baseline, at 1, 2, 3 and 6 months by the Functional Assessment of Cancer Therapy–Anemia (FACT–An). EPO responders patients were defined as having Hb level ≥12g/dl (EPO CR) or a ≥ 2g/dl increase [EPO partial response (EPO PR)] compared with baseline value without any transfusion requirement. The matching analysis took into account: sex, age, disease status, for the two groups, associated to cytogenetics, type of chemotherapy, sequential chemotherapy number for group 1, and diagnosis, conditioning, HSC source, number of previous transplants and GVHD for group 2.Between April 2006 and December 2009, among 261 screened patients, 55 were included in group1 and 61 in group 2, patient characteristics for each group are summarized in Table1. Main exclusion criteria were EPO contra-indication and patient refusal. The median number of EPO injections/patient was 13 (3 – 24) in group1 and 8 (2 - 28) in group 2. For the global population (111 evaluable patients [52 group1 and 59 in group 2]), we have noticed a significant improvement of QOL during the 6 months follow-up according to FACT-An anemia (p=0.01). Despite a non-significant improvement for FACT-G, we observed a significant improvement in physical well-being (p<0.0001). There were 85 EPO CR (83% in group1 and 71% in group 2) and 3 (6%) EPO PR (only in group1). Among patients who reached the 6 months follow-up, 81% had a normal Hb level. Fourteen patients (13%) were withdrawn (6 in group1 and 8 in group 2) due to EPO inefficacy and 9 in group 2 for relapse or EPO related/unrelated serious adverse events (AEs). In group1: the median time to achieve an EPO CR was 34 days (17-67) after first consolidation and 41 days (12-67) after second consolidation (p=0.35). In group 2: the median time to achieve EPO CR was 39 days (14 - 180). After the pair-matched analysis, 44 patients in each group were matched with at least one case-control patient. When comparing RBC and Pt transfusions, there were 712 units and 751 units in the matched population versus 504 and 669 in the EPO population respectively [208 spared RBC (80 in group1, p=0.008 and 128 in group 2, p=0.004) and 100 spared Pt units (all in group1, p=0.001)]. The multivariate analysis studying different confounding factors on the cumulative incidence of EPO CR showed a significant positive impact of younger age (p=0.001) and intensive chemotherapy (p=0.03) in group1; and for group 2, the positive impact of Pt levels at baseline, the negative impact of female recipient and major ABO incompatibility. We did not find any significant difference in terms of overall (OS) and event free survival (EFS) between EPO and control groups.This prospective study showed a real benefit of EPO administration on QOL, an achievement of a normal Hb level and a significant spare of RBC and Pt transfusions. Young AML patients, male allo-HSCT recipient, ABO compatible pairs seem to be the best candidates to benefit from EPO administration, with low AEs and no impact on OS or EFS. A cost-effectiveness study is ongoing and results will be communicated.No relevant conflicts of interest to declare.

Abstract 3810