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La prise d’un traitement immunosuppresseur a vie est obligatoire apres une transplantation. L’immunosuppression permet de prevenir le rejet du greffon par l’organisme receveur en limitant la reponse immunitaire acquise. Pourvoyeurs de nombreux effets indesirables, les immunosuppresseurs ont une marge therapeutique etroite et doivent faire l’objet d’un suivi particulier.

Resume Des recommandations specifiques a la nephrologie ont ete redigees sous l’egide de l’Association internationale de nephrologie pediatrique en 2011. Ces recommandations preconisent une transition individualisee, debutant entre 12 et 14 ans, avec des informations sur la maladie et les traitements du patient adaptees a l’âge et au niveau intellectuel. Les recommandations insistent sur l’importance d’identifier un referent pediatre et un referent en service adulte, ainsi qu’une equipe paramedicale et de travailleurs sociaux ; elles insistent egalement sur l’importance d’associer les aidants (les familles et l’entourage proche, etc.), la necessite d’un dossier specifique de transition et d’une visite prealable du service adulte avant le transfert. L’International Pediatric Nephrology Association recommande que le transfert soit realise au « bon moment » de la vie du jeune et non a ses 18 ans ; ce « bon moment » etant defini par le moment ou le jeune se sent pret, en periode de stabilite aussi bien medicale que familiale, scolaire et sociale. Afin de fournir au jeune des competences d’autogestion (empowerment) appropriees de sa maladie et de sa vie, dans le cadre de la filiere maladies renales rares (ORKiD), nous avons elabore un programme avec questionnaire adapte a l’âge en nous inspirant de celui mis en place a Southampton au Royaume-Uni. Ce document presente les outils developpes par le groupe de travail de la filiere de soins ORKiD.

Medication non-adherence (NA) after allogeneic hematopoietic cell transplantation (allo-HCT) can lead to serious complications. This study assesses NA in French adult and pediatric recipients and identifies factors associated with NA. In accordance with the EMERGE and STROBE guidelines, a cross sectional multicentric survey was conducted. We used a self-reported questionnaire that was adapted to adults and pediatrics and that could provide a picture of all three phases of medication adherence: initiation, implementation, persistence. We enrolled 242 patients, 203 adults (mean age: 51 years old, 50.7% male) and 39 children (mean age: 9 years old, 56.4% female). Reported NA was estimated at about 75% in both populations, adults and pediatrics. In adults, the univariate analysis showed that patients less than 50 years old (P = 0.041), (i) treated with cyclosporine (P = 0.02), (ii) treated with valacyclovir/acyclovir (P = 0.016), and (iii) experiencing side effects (P = 0.009), were significantly more non-adherent. In multivariate analysis, only recipient age was significantly associated to NA (P = 0.05). The limited size of the pediatric population did not allow us to draw any statistical conclusion about this population. To the best of our knowledge, this is the first study in France on NA in allo-HCT recipients. Our results highlight the age factor as the only factor related to NA. Further studies are needed to confirm our observations and refine results in pediatric populations, currently most at risk of medication NA.

The characterization of drug-drug interactions (DDIs) may require the use of several different tools, such as the thesaurus issued by our national health agency (i.e., ANSM), the metabolic pathways table from the Geneva University Hospital (GUH), and DDI-Predictor (DDI-P). We sought to (i) compare the three tools’ respective abilities to detect DDIs in routine clinical practice and (ii) measure the pharmacist intervention rate (PIR) and physician acceptance rate (PAR) associated with the use of DDI-P. The three tools’ respective DDI detection rates (in %) were measured. The PIRs and PARs were compared by using the area under the curve ratio given by DDI-P (RAUC) and applying a chi-squared test. The DDI detection rates differed significantly: 40.0%, 76.5%, and 85.2% for ANSM, GUH and DDI-P, respectively (p &lt, 0.0001). The PIR differed significantly according to the DDI-P’s RAUC: 90.0%, 44.2% and 75.0% for RAUC ≤ 0.5, RAUC 0.5–2 and RAUC &gt, 2, respectively (p &lt, 0.001). The overall PAR was 85.1% and did not appear to depend on the RAUC category (p = 0.729). Our results showed that more pharmacist interventions were issued when details of the strength of the DDI were available. The three tools can be used in a complementary manner, with a view to refining medication adjustments.

Objectives: Home-Based Hospital (HBH) services concern patients of all ages suffering from conditions requiring technical care, close clinical monitoring, or hospital treatments that would normally...

Cytomegalovirus is one of the main contributing factors to high mortality rates in patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT). The main factors of treatment failure are both drug resistance and intolerance. In some cases, Cytotect®CP CMV-hyperimmune globulin is used as salvage therapy. This study aims to investigate the safety and efficacy of Cytotect®CP as a salvage therapy in patients with CMV infection after allo-HCT. Twenty-three consecutive patients received Cytotect®CP for CMV infection after prior CMV therapy. At the time of Cytotect®CP introduction, 17 patients (74%) had developed acute GVHD and 15 patients (64%) were receiving steroid treatment; Cytotect®CP was used as monotherapy (n = 7) and in combination (n = 16). Overall, response was observed in 18 patients (78%) with a median time of 15 days (range: 3-51). Of the 18 responders, 4 experienced CMV reactivation, while 5 responders died within 100 days of beginning treatment. Of these 5 deaths, 4 were due to causes unrelated to CMV. Estimated 100-day OS from the introduction of Cytotect®CP was 69.6%. No statistically significant difference was observed in 100-day OS between responders and non-responders (73.7% vs 50.0%, p = 0.258). Cytotect®CP as salvage therapy is effective and well-tolerated. Given its safety profile, early treatment use should be considered.

Resume Introduction Le patient greffe renal est expose a un risque accru de iatrogenie medicamenteuse (IM). Le but de l’etude est de mesurer l’impact des interventions du pharmacien clinicien sur l’IM evitable. Materiel et methode Les cas d’IM ont ete recueillis sur 3 periodes : sans intervention, avec conciliation medicamenteuse (CM) d’entree, et avec une CM d’entree et entretien pharmaceutique de sortie. Les cas d’IM ont ete classes selon leur nature, leur gravite et leur evitabilite. Resultats Les patients inclus etaient majoritairement des hommes, d’environ 55 ans, en stade 3 d’IRC, greffes depuis moins de 3 mois ou depuis plus d’un an, avec des facteurs de risque cardiovasculaire, une nephropathie polykystique et en moyenne 9 medicaments/jour. Vingt pour cent des cas d’IM etaient evitables et majoritairement graves. A la periode 1, 27,7 % des patients presentaient au moins un cas d’IM, 21,3 % a la periode 2, et 17,4 % a la periode 3 (p = 0,03). Cent dix patients ont eu une CM a l’entree avec en moyenne 0,6 divergence non intentionnelle/patient. Elle portait surtout sur des oublis de medicament (81 %) et concernait des medicaments des voies digestives et metaboliques (24,5 %), du systeme cardiovasculaire (23 %) et du systeme nerveux (23 %). Soixante-huit entretiens pharmaceutiques de sortie ont ete realises, revelant des pratiques d’automedication. Conclusion Notre etude montre qu’une CM d’entree associee a un entretien pharmaceutique de sortie pourrait etre benefique pour reduire l’IM chez le patient greffe renal. Il serait licite d’envisager une etude specifique pour conforter ces resultats.

Resume Le pharmacien d’officine est reconnu comme un acteur de la prevention et de l’education therapeutique. Un projet pedagogique mene dans les officines du Nord-Pas-de-Calais et coordonne par la faculte de pharmacie de Lille avec le reseau Nephronor nous a permis de collecter des donnees afin d’etudier l’interet d’une evaluation pharmaceutique officinale de la MRC. Nous rapportons ici le resultat de l’intervention realisee dans 109 pharmacies d’officine. Les entretiens pharmaceutiques ont concerne 2 populations de patients. Le groupe A comprenant des patients se connaissant porteurs d’une IRC (entretien pharmaceutique d’optimisation therapeutique). Le groupe B regroupe des patients a risque de MRC pour lesquels est proposee une strategie de depistage. Ainsi, 354 patients ont ete inclus dans le groupe A, majoritairement des femmes (51,2 %), en stade 3 d’IRC, d’âge moyen 73 ans, diabetiques (44 %). Environ 70 % des patients avaient deja ete vus par un nephrologue et 45 % d’entre eux presentaient une bonne adhesion therapeutique selon le questionnaire de Morisky-Green. Par ailleurs, 20 % des patients n’avaient pas de traitement nephroprotecteur en stades 3 et 4 de la MRC, et plus de la moitie ne connaissaient pas les situations a risque d’insuffisance renale aigue. Le groupe B a inclus 532 patients (âge moyen 70 ans). L’intervention pharmaceutique a permis de depister 10 % de patients avec un DFG 2 . L’entretien pharmaceutique en officine a permis d’optimiser la prise en charge therapeutique et l’information des patients IRC, ainsi que le depistage precoce chez certains patients a risque.

Background: Pharmacists have been involved in the care of transplant recipients for several decades, and a growing body of literature shows the beneficial effects of clinical pharmacist care on important outcomes for these patients. Objectives: The primary objective was to describe the roles and impacts of pharmacists in a solid organ transplant setting. The secondary objective was to describe and rate the pharmacists’ interventions.Data Sources: Three databases —PubMed, Embase, and Evidence-Based Medicine Reviews —were searched from January 1, 1990, to June 16, 2015. Study Selection and Data Extraction: All studies addressing the roles of pharmacists and the impacts of clinical pharmacy services on the care of solid organ transplant recipients were considered. Only studies providing a statistical analysis were included. Design, setting, sample size, patient characteristics, pharmacists’ interventions, study bias, and outcomes were extracted for analysis. Data Synthesis: Four randomized controlled trials, 4 cohort studies, 3 pre–post studies, and 1 quasi-randomized controlled trial were included in the review, representing a total of 1837 patients. Of the 12 studies included, 8 specifically focused on renal transplant, and 1 each focused on liver, lung, abdominal organ, and general solid organ transplant. The pivotal pharmacist activities leading to the main patient outcomes were medication counselling (n = 8 studies), medication reconciliation (n = 5), and reviewing and optimizing drug therapy (n = 3). Improvements to medication adherence (n = 6 studies), morbidity (n = 4), costs (n = 2), and medication errors (n = 2) were reported.Conclusion: Currently available evidence suggests that pharmacists can improve patient outcomes in the solid organ transplant setting. Adherence, morbidity, costs, and medication errors were identified as the main outcomes that were improved by pharmaceutical interventions. Transplant programs need to invest more in this resource.RÉSUMÉContexte : Les pharmaciens participent aux soins des greffés depuis plusieurs décennies et un nombre croissant de publications révèlent les effets bénéfiques des soins prodigués par les pharmaciens cliniciens quant aux résultats thérapeutiques importants pour ces patients. Objectifs : L’objectif principal était de décrire les rôles des pharmaciens et leurs influences par rapport aux greffes d’organes solides. L’objectif secondaire était de décrire et d’évaluer les interventions des pharmaciens.Sources des données : Les bases de données PubMed, Embase et Evidence-Based Medicine Reviews ont été interrogées pour la période allant du 1er janvier 1990 au 16 juin 2015. Sélection des études et extraction des données : Toutes les études abordant les rôles des pharmaciens et l’influence des services de pharmacie clinique sur les soins des receveurs d’organes solides ont été prises en considération. Seules les études présentant des analyses statistiques ont été retenues. Le plan d’étude, le contexte, la taille de l’échantillon, les caractéristiques des patients, les interventions des pharmaciens, les biais et les résultats thérapeutiques ont servi à l’analyse. Synthèse des données : Quatre études contrôlées à répartition aléatoire, 4 études de cohorte, 3 études avant-après et 1 essai comparatif à répartition quasi-aléatoire ont été retenus pour l’analyse, ce qui représentait au total 1837 patients. Parmi les 12 études retenues, 8 abordaient spécifiquement la greffe rénale et chacune des 4 autres concernait respectivement une greffe hépatique, une greffe pulmonaire, une greffe d’organe abdominal et une greffe d’organe solide. Les activités clés des pharmaciens menant aux principaux résultats thérapeutiques étaient les conseils sur les médicaments (n = 8 études), l’établissement du bilan comparatif des médicaments (n = 5) ainsi que l’examen et l’optimisation de la pharmacothérapie (n = 3). On a constaté des améliorations des taux d’observance pharmaco -thérapeutique (n = 6 études), des taux de morbidité (n = 4), des coûts (n = 2) et des taux d’erreurs de médicaments (n = 2).Conclusion : Les données probantes disponibles laissent croire que les pharmaciens peuvent améliorer les résultats thérapeutiques en ce qui concerne les greffes d’organes solides. Les taux d’observance pharmaco -thérapeutique, les taux de morbidité, les coûts et les taux d’erreurs de médicaments ont été désignés comme les résultats principaux qui ont été améliorés par les interventions pharmaceutiques. Les programmes de greffe doivent investir davantage dans cette ressource.

International audience; INTRODUCTION: Drug related problems (DRP) can lead to severe consequences in kidney recipients. The aim of the study was to assess the impact of the clinical pharmacist interventions on the incidence of DRP. METHOD: The number of DRP were evaluated according to 3periods: Without intervention, with medication reconciliation at admission, and with medication reconciliation at admission associated with an interview with the clinical pharmacist at discharge. RESULTS: Patients concerned were mainly men, 55years old (median age), stage3 of CKD, transplanted for less than 3months or more than 1year, with cardiovascular risk factors and receiving an average of 9drugs/day. Among the DRP, 20% were avoidable and severe in most cases. In period1, 27.7% patients had at least 1DRP, in period2, 21.3% patients had at least 1DRP, and in period3, 17.4% of patients had at least 1DRP (P=0.03). One hundred and ten patients had medication reconciliation at admission with a mean of 0.6unintentional discrepancies per patient (omission in 81% of cases). The main drugs involved concerned the digestive-metabolic (24.5%), cardiovascular (23%), and nervous (23%) system. Sixty-eight interviews at discharge were realized and revealed self-medication habits. CONCLUSION: Our study shows that medication reconciliation at admission associated with an interview with the clinical pharmacist at discharge can help to reduce DRP in kidney recipients. Further studies are needed to confirm our results.

The study of calcineurin inhibitor (CNI) blood level variability to evaluate adherence in transplantation has improved over the years. The aim of our study was to assess factors associated with this variability using the coefficient of variation (CV). A cross-sectional sample of kidney recipients grafted for more than 1 year was recruited. We recorded clinical data, data from a clinical pharmacist interview and from six questionnaires measuring adherence, satisfaction, behaviours, beliefs, perception of the illness and social vulnerability. A total of 408 recipients were enrolled (61.2% male, mean age 54) and divided into two groups: low variability CV

Resume Dans une demarche qui vise a uniformiser les procedures d’allogreffe de cellules souches hematopoietiques (CSH), la Societe francaise de greffe de moelle et de therapie cellulaire (SFGM-TC), a organise les quatriemes ateliers d’harmonisation des pratiques en septembre 2013 a Lille. Dans cet atelier nous abordons les immunosuppresseurs utilises dans la prevention de la reaction du greffon contre l’hote : rapport de la SFGM-TC.

Background Medication non-adherence is a major issue after transplant that can lead to misdiagnosis, rejection, poor health affecting quality of life, graft loss or death. Several estimations of adherence and related factors have previously been described but conclusions leave doubt as to the most accurate assessment method. Aim of the review To identify the factors most relevant to medication non-adherence in kidney transplant in current clinical practice. Method This systematic review is registered in the PROSPERO data base and follows the Prisma checklist. Articles in English in three databases from January 2009 to December 2014 were analysed. A synthesis was made to target adherence assessment methods, their prevalence and significance. Results Thirty-seven studies were analysed rates of non-adherence fluctuating from 1.6 to 96%. Assessment methods varied from one study to another, although self-reports were mainly used. It appears that youth (≤50 years old), male, low social support, unemployment, low education, ≥3 months post graft, living donor, ≥6 comorbidities, ≥5 drugs/d, ≥2 intakes/d, negative beliefs, negative behavior, depression and anxiety were the factors significantly related to non-adherence. Conclusion As there are no established guidelines, consideration should be given to more than one approach to identify medication non-adherence although self-reports should remain the cornerstone of adherence assessment.

To harmonize clinical practice in hematopoietic stem cell transplantation, the Francophone Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the sixth annual series of workshops which brought together practitioners from all member centers and took place in September 2015 in Lille. The main aim of this session was to describe the impact, evaluation and treatment of post-transplant iron overload.

Background Drug-related problems (DRPs) are common in chronic kidney disease (CKD) patients. We developed a 2-step consultation including a clinical pharmacist (CP) session and a nephrologist conventional care consultation to explore the feasibility of a pilot drug-oriented disease management program in controlling iatrogenic side effects. Methods Drug inventory was estimated by a CP before each nephrology consultation. CP interventions were based on the French Society of Clinical Pharmacy intervention tools. Results In this 6-month prospective study, 67 CKD patients were enrolled: 77% with stage 3 or 4 CKD (by Kidney Disease Improving Global Outcomes criteria), 66% males, 76% with diabetes, median age 70 years (range 59-75), with a mean 2.6 ± 1.2 comorbidities and 10 ± 3.5 medications. We registered 142 DRPs, in 93% of patients, which mainly concerned untreated indications (31.7%) and incorrect dosages (19%). The most frequent pharmaceutical interventions concerned addition of drug (34%) and adaptation of dose (25.5%). The main drugs involved concerned the cardiovascular (33%), digestive-metabolic (26.9%) and hematopoietic (19.9%) systems. DRPs correlated significantly with a higher number of medications (p=0.049) and with older patient age (p=0.0027). Furthermore, patients' knowledge was evaluated in 41 patients (61%) by the CP with a systematic questionnaire. Three at-risk situations were described: 80.5% of patients interviewed were unaware of the beneficial impact of their treatment, 85% were not aware of medical situations at risk and 68% declared self-medication habits. Conclusion A formatted CP evaluation coupled with a renal consultation was able to detect a higher level of DRPs, to reinforce educational messages and to propose immediate changes in the therapeutic project.

Lung allograft airway colonization by Aspergillus species is common among lung transplant recipients. We report the case of a 46-year-old female lung transplant outpatient diagnosed with persistent pulmonary Aspergillus colonization (>50 colonies of Aspergillus terreus) 3 months after lung transplantation. Oral voriconazole 200 mg twice a day (b.i.d) was initiated shortly after diagnosis. Two days after voriconazole initiation, alkaline phosphatase (ALP), alanine transaminase (ALT), and aspartate transaminase (AST) were normal or slightly elevated (79, 37, and 21 UI/L, respectively). Ten days after the first voriconazole administration, these values started to increase. Maximum levels were reached after 20 days for ALP (369 UI/L) and at around 30 days for ALT and AST (223 and 188 UI/L, respectively). Instead of discontinuing antifungal therapy, it was decided to reduce the voriconazole dose to 100 mg b.i.d. This asymptomatic progressive cholestatic hepatitis resolved, and 10 days after dose reduction ALP, ALT, AST were at 136, 53, and 28 UI/L, respectively. Finally, therapeutic drug monitoring revealed adequate voriconazole plasma trough concentrations (0.98 mg/L) 30 days after dose reduction and no more colonies of Aspergillus were observed. Voriconazole-induced hepatotoxicity is a well known dose-dependent adverse drug reaction. This experience confirms the appropriateness of voriconazole dose reduction instead of therapy interruption in dose-dependent moderate liver toxicity. Voriconazole therapeutic drug monitoring before and after dose reduction may help to avoid drug accumulation and inappropriately low drug exposure, respectively.

We report the case of a 49-year-old renal and pancreatic female transplant recipient, who presented a drug interaction between tacrolimus, warfarin and pristinamycin. Three days after oral pristinamycin 1000 mg bid administrations, the patient presented nausea, vomiting, abdominal pain and violent headaches that required hospitalization. Tacrolimus trough level was 5 times higher (34.9 μg/l) than the target required (5-8 μg/l) and the INR was at 5.8 (therapeutic index between 2 and 3) despite a stable kidney function (serum creatinine 130 μmol/L) and no other organic disorders. Five days following discontinuation, drug monitoring revealed adequate tacrolimus plasma trough concentrations (8.9 μg/l) and the INR subsequently decreased. Pristinamycin is an antibiotic effective against the majority of Gram positive bacteria. This drug is an inhibitor of the multidrug transporter P-glycoprotein (P-gp) that could lead to the accumulation of tacrolimus. Moreover, pristinamycin IIA is the active metabolite of quinupristin/dalfopristin which, is known to be an inhibitor of cytochrome P450 3A4 (CYP 3A4). Our case supposes that pristinamycin is also an inhibitor of CYP 3A4 that can lead to an increase of tacrolimus levels. This case report brings to light potential drug interactions of pristinamycin with narrow therapeutic index drugs such as tacrolimus and warfarin.

Background Clinical pharmacists (CPs) specifically manage lab-test follow-up, adapt drug dosage according to guidelines and evaluate cardiovascular risk factors and decline in renal function. The aim of this study was to assess the impact of clinical pharmacy services in outpatient nephrology clinics. Method For each patient, medical history and current treatment were obtained. Each intervention was classified according to the Act-IP document of the French Society of Clinical Pharmacy. This tool contains identifications and guidelines for prevention and resolution of drug-related problems (DRPs). Results From January 2008 until April 2009, 42 patients seen by the CP on at least 2 visits were included in the study. We observed 350 pharmaceutical consultations and 263 interventions. The pharmaceutical interventions concerned: untreated indication (30%), underdosage (25.9%) and overdosage (18.3%). The CP interventions consisted of: adapting doses (42.2%) and adding treatments (31.9%). The main drugs involved concerned the cardiovascular (33.1%), digestive-metabolic (28.6%) and hematopoietic (21.6%) systems. Conclusion The inclusion of a CP in the management of chronic kidney disease (CKD) patients is necessary for identification and prevention of DRPs. Besides the medical improvement of CKD patients, the CP participates in the development of prescription recommendations and therapeutic education programs for patients. Moreover, redefining roles and practices of members of a clinical team proved its efficiency in optimizing the medical care of CKD patients. Furthermore, patient entry into dialysis is postponed, which leads to a reduction in costs for health care insurance.