Adaptative Strategy of Immunosuppressive Drugs Dosage Adjustments When Combined With Nirmatrelvir/Ritonavir in Solid Organ Transplant Recipients With COVID-19.

Nirmatrelvir/ritonavir is a promising option for preventing severe COVID-19 in solid organ transplant recipients with SARS-CoV-2 infection. However, concerns have arisen regarding potential drug interactions with calcineurin inhibitors (CNI). This two-phase multicentre retrospective study, involving 113 patients on tacrolimus and 13 on cyclosporine A, aimed to assess the feasibility and outcomes of recommendations issued by The French societies of transplantation (SFT) and pharmacology (SFPT) for CNI management in this context. The study first evaluated adherence to recommendations, CNI exposure, and clinical outcomes. Notably, 96.5% of patients on tacrolimus adhered to the recommendations, maintaining stable tacrolimus trough concentrations (C0) during nirmatrelvir/ritonavir treatment. After reintroduction, most patients experienced increased C0, with 42.9% surpassing 15 ng/mL, including three patients exceeding 40 ng/mL. Similar trends were observed in cyclosporine A patients, with no COVID-19-related hospitalizations. Moreover, data from 22 patients were used to refine the reintroduction strategy. Modelling analyses suggested reintroducing tacrolimus at 50% of the initial dose on day 8, and then at 100% from day 9 as the optimal approach. In conclusion, the current strategy effectively maintains consistent tacrolimus exposure during nirmatrelvir/ritonavir treatment, and a stepwise reintroduction of tacrolimus may be better suited to the low CYP3A recovery.

Does DDI-Predictor Help Pharmacists to Detect Drug-Drug Interactions and Resolve Medication Issues More Effectively?

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 (The National Agency for the Safety of Medicines and Health Products), GUH and DDI-P, respectively (p < 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 > 2, respectively (p < 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.

Medication non-adherence after allogeneic hematopoietic cell transplantation in adult and pediatric recipients: a cross sectional study conducted by the Francophone Society of Bone Marrow Transplantation and Cellular Therapy.

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.

Clinical pharmacist and pharmaceutical interventions in HBH unit: a French observational study.

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 be provided during hospitalisation. Drug-related problems are common in chronically-ill patients and many such events are preventable. Nevertheless, little data is available for outpatients, especially for HBH unit patients. The aim of the study was to assess the rates and types of drug-related problems prevented and resolved by the clinical pharmacist in a Home-Based Hospital unit.Methods: The drug-related problems were registered prospectively by the clinical pharmacist from May 2011 to April 2015. These pharmaceutical interventions were analysed according to the intervention tool recommended by the French Society of Clinical Pharmacy (Act IP).Results: 20,195 medication prescriptions relating to 2,878 patients were analysed. We registered 388 drug-related problems involving 267 patients (71.2% female; mean age 32.1 ± 29.7 years), mainly concerning untreated conditions (24.2%), drugs used without indications (14.7%), non-conformity to guidelines or contra-indication (12.6%) and drug monitoring (12.4%). Pharmaceutical interventions involved 186 drugs, mainly for hematopoiesis, infections and the digestive system (34%, 16.5%, and 14.6%, respectively). 87.6% of the pharmacist's recommendations were accepted.Conclusions: A formatted clinical pharmacist evaluation was able to detect a high level of drug-related problems, and prevent complications in patients cared for by a Home-Based Hospital unit.

Roles and Impacts of the Transplant Pharmacist: A Systematic Review.

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.

CONTEXTE: 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 1cr 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 pharmacothérapeutique (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 pharmacothérapeutique, 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.

Cytotect®CP as salvage therapy in patients with CMV infection following allogeneic hematopoietic cell transplantation: a multicenter retrospective study.

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.

[Clinical pharmacist and medication reconciliation in kidney transplantation]. / Impact du pharmacien clinicien sur la iatrogénie médicamenteuse chez le patient greffé rénal.

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.

Factors associated with the variability of calcineurin inhibitor blood levels in kidney recipients grafted for more than 1 year.

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 < 30% (n = 302), high variability CV ≥ 30% (n = 106). In univariate analysis, hospital-home distance, cyclosporine, time since transplantation and presence of discrepancies in drug regimen were associated with a greater risk of CV ≥ 30%. In contrast, tacrolimus QD conferred a lower risk of CV ≥ 30%. In multivariate analysis, only the presence of discrepancies remained significant: (OR 3.2 [1.21-9.01]; P = 0.022). Discrepancies in drug regimen appear as the main risk factor associated with CNI blood variability. The clinical pharmacist's input is an accurate and simple way of detecting non-adherence which is not revealed in self-report questionnaires.

Factors relevant to medication non-adherence in kidney transplant: a systematic review.

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.

[Community pharmacists' interventions to prevent and screen chronic kidney disease patients]. / Implication du pharmacien d'officine dans le parcours de soins de la maladie rénale chronique.

Chronic kidney disease (CKD) is a major concern of public health. The pharmacist is known as a health practitioner involved in prevention and therapeutic education. Our study aimed at defining the impact of community pharmacists' interventions for preventing and screening CKD. In our observational prospective study of 5 months conducted in 109 community pharmacy, we included 2 groups of patients: A (therapeutic optimization): CKD patients and B (CKD screening): population at risk. In group A, we included 354 patients, mainly women (51.2%), in stage 3 of CKD, mean age 73 years old, with hypertension alone (40.6%) or associated with diabetes (44%). About 70% of the patients had a follow up by a nephrologist and 45% of them were good adherent according to the Morisky-Green self-report. However, approximately 20% of patients did not have nephroprotective treatments in their regimen although they were on stage 3 or 4 CKD patients, and about half of them were not aware of medical situations at risk. Concerning group B, 532 patients were included. The pharmaceutical interventions screened 10% of patients with a GFR<60mL/min/1.73m2. The community pharmacists' interventions helped to optimize the therapeutic management of CKD patients and in the early screening of patients at risk. More studies are needed to extrapolate our observations to a larger population.

[Assessment and management of post-transplant iron overload: Guidelines of the Francophone Society of Marrow Transplantation and Cellular Therapy (SFGM-TC)]. / Évaluation et prise en charge de la surcharge en fer post-greffe : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC).

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.

Identification of drug-related problems in ambulatory chronic kidney disease patients: a 6-month prospective study.

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.

Pharmaceutical care in chronic kidney disease: experience at Grenoble University Hospital from 2006 to 2010.

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.