Prioritizing Quality over Quantity: Defining Optimal Pharmacist-to-Patient Ratios to Ensure Comprehensive Direct Patient Care in a Medical or Surgical Unit.

Background: The expanding scope of practice of hospital pharmacists has contributed to improvements in patient care; however, workload remains a barrier to the provision of optimal pharmaceutical care. Established ratios to guide clinical pharmacy staffing on medical and surgical units are lacking in Canada. Objectives: To determine the pharmacist-to-patient ratio that allows for provision of comprehensive pharmaceutical care to each patient on a medical or surgical unit and to determine which comprehensive care tasks can be delivered in settings where staffing is limited. Methods: A multiphase study was conducted in 6 hospitals. First, a modified Delphi study was conducted to define and prioritize the elements of comprehensive pharmaceutical care. Next, a work sampling study was conducted to establish the frequency of each task and the time required for completion. Finally, a workforce calculator was used to determine pharmacy staffing ratios. Results: Ten pharmacists participated in the modified Delphi study, and 31 participated in the work sampling study. A total of 15 comprehensive care tasks were identified, 7 of which were categorized as tasks to prioritize in settings where staffing is limited. The optimal staffing ratios were 1 pharmacist to 13 patients in internal medicine teaching units, 1 pharmacist to 26 patients in hospitalist or internal medicine nonteaching units, and 1 pharmacist to 14 patients in surgical units. Conclusions: The optimal staffing ratios determined in this study should enable pharmacists to provide comprehensive care to each patient. Implementing these staffing ratios could increase the consistency of clinical pharmacy services, improve patient outcomes, and improve pharmacists' work satisfaction. Further research is required to validate these ratios in a variety of settings.

Contexte: L'élargissement du champ d'exercice des pharmaciens d'hôpitaux a contribué à l'amélioration des soins aux patients; cependant, la charge de travail reste un obstacle à la prestation de soins pharmaceutiques optimaux. Il n'existe pas de ratios établis pour guider la dotation en pharmacie clinique dans les unités médicales et chirurgicales au Canada. Objectifs: Déterminer le ratio pharmacien-patient permettant de fournir des soins pharmaceutiques complets à chaque patient dans une unité médicale ou chirurgicale donnée et déterminer quelles tâches de soins complets peuvent être dispensées dans des contextes où le personnel est limité. Méthodes: Une étude multiphase a été menée dans 6 hôpitaux. Tout d'abord, une étude Delphi modifiée a été menée pour définir et hiérarchiser les éléments d'une prise en charge pharmaceutique générale. Ensuite, une étude par échantillonnage de travaux a été menée afin d'établir la fréquence de chaque tâche et le temps nécessaire pour l'accomplir. Enfin, un calculateur d'effectifs a été utilisé pour déterminer les ratios de dotation en pharmacie. Résultats: Dix pharmaciens ont participé à l'étude Delphi modifiée et 31 ont participé à l'étude par échantillonnage de travail. Au total, 15 tâches de soins complets ont été identifiées, dont 7 ont été classées comme des tâches à prioriser dans des contextes où le personnel est limité. Les ratios d'effectifs optimaux étaient de 1 pharmacien pour 13 patients dans les unités d'enseignement de médecine interne, de 1 pharmacien pour 26 patients dans les unités non pédagogiques hospitalières ou de médecine interne et de 1 pharmacien pour 14 patients dans les unités chirurgicales. Conclusions: Les ratios d'effectifs optimaux déterminés dans cette étude devraient permettre aux pharmaciens de prodiguer des soins complets à chaque patient. Les mettre en œuvre pourrait accroître la cohérence des services de pharmacie clinique, améliorer les résultats pour les patients ainsi que la satisfaction au travail des pharmaciens. Des recherches supplémentaires sont nécessaires pour valider ces ratios dans divers contextes.

48-hour Induction of Transdermal Buprenorphine to Extended-release Buprenorphine.

ABSTRACT: Buprenorphine extended-release (BUP-XR) provides sustained delivery of buprenorphine to control withdrawal and craving symptoms in the form of a monthly injectable and has been shown to improve health outcomes in patients with opioid use disorder. It is recommended that patients are stabilized with a transmucosal buprenorphine product, for at least 7 days per the product monograph; however, clinically, this timeline may be expedited. We report a case of a hospitalized patient with unregulated fentanyl use who underwent a successful transdermal buprenorphine induction for 48 hours to initiate BUP-XR with minimal levels of withdrawal and without precipitating opioid withdrawal. The approach described could provide a practical, patient-centered, accelerated induction strategy that, once independently validated, could considerably facilitate the use of BUP-XR.

Pathways to Developing Clinical Pharmacist Practitioners: Is There a Better Way Forward? (Path-CPP).

Background: Clinical Pharmacist Practitioners (CPPs) are independent care providers who practise to their full scope and have a positive impact on the quality of patient care. Ideally, all pharmacists in Canada would perform at this level. However, there is significant diversity in pharmacy practice across the country and among practice settings. It would be valuable to better understand how pharmacists attain CPP-level practice and what strategies might enable more pharmacists to practise at this level. Objectives: To understand the perceptions of current CPPs and stakeholders in the health care system regarding the status of the CPP role in Canada and to propose pathways that would facilitate the attainment and recognition of CPP-level practice. Methods: A qualitative study was conducted using semistructured interviews of peer-nominated CPPs and health care system stakeholders. Interviews were recorded, transcribed, and then analyzed using thematic analysis. Results: Interviews involving 13 CPPs and 6 health care system stakeholders, conducted between March and July 2020, yielded 3 theme categories related to CPP roles, each containing subthemes, and 3 distinct themes relating to pathways forward. The 3 pathway themes were the following: that a legislative solution for expanded pharmacist scope is needed, that a new degree program is not required for pharmacy in Canada, and that a unified national credential signifying high-level practice might allow for better recognition of CPPs. Conclusions: The full potential of pharmacists practising with advanced scope of practice in Canada has yet to be realized. Although significant external challenges exist, pharmacists must reframe the narrative by clearly articulating and defining their role within the Canadian health care system to increase CPP-level practice.

Contexte: Les praticiens cliniciens sont des prestataires de soins indépendants qui exercent toutes leurs compétences et ont une incidence positive sur la qualité des soins aux patients. Idéalement, tous les pharmaciens au Canada devraient exercer à ce niveau. Cependant, la pratique de la pharmacie diffère grandement au pays et selon le milieu d'exercice. Il serait utile de mieux comprendre comment les pharmaciens atteignent le niveau de pratique de praticiens clinicien et quelles stratégies pourraient permettre à davantage d'entre eux d'exercer à ce niveau. Objectifs: Comprendre les perceptions des praticiens cliniciens actuels et des parties prenantes du système de soins de santé concernant le statut du rôle des praticiens cliniciens au Canada et proposer des voies visant à faciliter la réalisation de la pratique au niveau de praticien clinicien et la reconnaissance de celle-ci. Méthodes: Une étude qualitative a été menée à l'aide d'entretiens semi-structurés avec des praticiens cliniciens désignés par leurs pairs et des parties prenantes du système de soins de santé. Les entretiens ont été enregistrés, retranscrits, puis analysés à l'aide d'une analyse thématique. Résultats: Des entretiens impliquant 13 praticiens cliniciens et 6 parties prenantes du système de soins de santé, menés entre mars et juillet 2020, ont permis de distinguer trois catégories thématiques liées aux rôles des praticiens cliniciens, chacune contenant des sous-thèmes, ainsi que trois thèmes distincts concernant les voies à suivre. Ces trois derniers thèmes étaient les suivants : la nécessité d'une solution législative pour l'élargissement du champ des compétences des pharmaciens; le fait qu'un nouveau programme diplômant ne soit pas requis pour la pharmacie au Canada; et l'idée qu'une accréditation nationale unifiée signifiant une pratique de haut niveau pourrait permettre de mieux reconnaître les praticiens cliniciens. Conclusions: Le plein potentiel des pharmaciens exerçant avec une portée de pratique avancée au Canada reste encore à réaliser. Malgré l'existence de défis externes importants, les pharmaciens doivent reformuler le récit en articulant et en définissant clairement leur rôle au sein du système de soins de santé canadien afin d'accroître la pratique au niveau de praticien clinicien.

Safety of administering cefazolin versus other antibiotics in penicillin-allergic patients for surgical prophylaxis at a major Canadian teaching hospital.

BACKGROUND: Cefazolin surgical prophylaxis is associated with better patient outcomes; however, its use in penicillin-allergic patients is controversial. We evaluated the safety of cefazolin as surgical prophylaxis in penicillin-allergic patients, including those with anaphylaxis histories. METHODS: We conducted a pre and postintervention quality improvement evaluation of an institution-wide policy change at a tertiary-care hospital, before (October 2017-January 2018), during (February 2018-September 2018), and after (October 2018-October 2019) transition to routine cefazolin prophylaxis for penicillin-allergic patients, including those with anaphylaxis histories but excluding severe delayed reactions (eg, Stevens-Johnson syndrome). Retrospective data was collected on all surgical prophylaxis patients with penicillin-anaphylactic histories between October 2017 and September 2018. From October 2018, we prospectively reviewed adverse events with cefazolin. Primary outcome was adverse events in penicillin-allergic patients receiving cefazolin perioperatively. RESULTS: From October 2017 to October 2019, 27,467 operations were performed. Of 220 patients with penicillin-anaphylactic histories reviewed prior to the full policy change, no statistically significant differences were reported in allergic reactions (P = .70), surgical site infections (P = 1.00), or adverse events (P = .32) with cefazolin compared to other antibiotics. Postpolicy implementation, cefazolin usage increased 18.2%, while vancomycin and clindamycin decreased by 11.4% and 62.0%, respectively. No anaphylaxis was documented in penicillin-allergic patients receiving cefazolin in either the review or quality assurance follow-up after the change. Of 3 patients developing reactions to cefazolin, none had histories of penicillin allergy. Surgical site infection rates were similar between pre and postpolicy time periods (P = .842). CONCLUSION: Administration of cefazolin in penicillin-anaphylactic patients for surgical prophylaxis appears to be safe.

How Hospital Pharmacists Spend Their Time: A Work-Sampling Study.

BACKGROUND: The expanded scope of pharmacist practice allows for increased comprehensive care and improved patient outcomes at the cost of increased workload and time demands on pharmacists. There are limited descriptive metrics for the time that pharmacists spend on various activities during the workday. An evaluation of the time spent on different activities would allow for potential optimization of workflow, with a focus primarily on devoting more time to direct patient care activities. OBJECTIVE: To quantify the amount of time that hospital and clinic-based pharmacists spend on clinical activities, including direct and indirect patient care, and nonclinical activities. METHODS: An observational fixed-interval, work-sampling study was conducted at 2 hospitals, Vancouver General Hospital and Richmond Hospital, both in British Columbia. Trained observers followed individual pharmacists for a set period. The pharmacists' activities were recorded in 1-min increments and classified into various categories. RESULTS: In total, 2044 min of activity, involving 11 individual pharmacists, were observed. Clinical activities accounted for 82% of total time, 12% (251 min) on direct patient care activities and 70% (1434 min) on indirect patient care activities. The most common direct clinical activity was conducting patient medication history interviews (73 min; 4% of total time), and the most common indirect clinical activity was assessment and evaluation (585 min; 29%). The most common nonclinical activities were walking (91 min; 4% of total time), looking for something (57 min; 3%), and teaching pharmacy students on practicum (60 min; 3%). CONCLUSIONS: Although the pharmacists spent most of their time on clinical activities, face-to-face time with patients (direct clinical activities) seemed low, which highlights an area for potential improvement. The pharmacists spent much more time documenting information in pharmacy-specific monitoring forms (i.e., assessment and evaluation) than they spent writing notes or recommendations in the chart, for sharing with other health care professionals.

CONTEXTE: L'élargissement du champ d'activité du pharmacien permet d'améliorer la qualité des soins et les résultats pour le patient au prix d'une augmentation de la charge et du temps de travail des pharmaciens. Il existe peu de mesures descriptives temps que les pharmaciens consacrent à leurs diverses activités de la journée. Une évaluation de ce temps permettrait d'optimiser le flux de travail afin que l'accent puisse être mis principalement sur l'augmentation du temps réservé aux activités de soins directs des patients. OBJECTIF: Quantifier le temps que passent les pharmaciens des hôpitaux et des cliniques à effectuer des activités cliniques, y compris des activités de soins directs et indirects, ainsi que des activités non cliniques. MÉTHODES: Une étude observationnelle par échantillonnage à intervalles fixes a été menée dans deux hôpitaux : le Vancouver General Hospital et le Richmond Hospital, tous deux en Colombie-Britannique. Des observateurs formés ont suivi chaque pharmacien en particulier pendant une période déterminée. Leurs activités étaient consignées par tranches d'une minute et classées en diverses catégories. RÉSULTATS: L'observation a porté sur des activités totalisant 2044 minutes réparties entre 11 pharmaciens. Les activités cliniques représentaient 82 % du temps total, 12 % (251 min) des activités étaient consacrées aux soins directs et 70 % (1434 min), aux soins indirects. L'activité clinique directe la plus courante consistait à mener des entrevues portant sur les antécédents pharmacothérapeutiques des patients (73 min, 4 % du temps total) et l'activité clinique indirecte la plus courante était l'évaluation (585 min, 29 %). Les activités non cliniques les plus courantes étaient la marche (91 min, 4 % du temps total), la recherche de quelque chose (57 min, 3 %) et la formation des étudiants stagiaires en pharmacie (60 min, 3 %). CONCLUSIONS: Bien que les pharmaciens consacrent la plus grande partie de leur temps à des activités cliniques, le temps passé auprès des patients (activités cliniques directes) semblait faible, ce qui indique une possibilité d'amélioration. Les pharmaciens passent beaucoup plus de temps à consigner de l'information dans des formulaires de contrôle spécifiques à la pharmacie (c.-à-d. évaluation) qu'à rédiger des notes ou des recommandations dans les tableaux pour les partager avec les autres professionnels de la santé.

Regression and Genomic Analyses on the Association Between Dose-Normalized Mycophenolic Acid Exposure and Absolute Neutrophil Count in Steroid-Free, De Novo Kidney Transplant Recipients.

BACKGROUND AND OBJECTIVES: The hematological side effects associated with mycophenolic acid (MPA) are relatively common and have severe consequences. The majority of literature data have not shown clear consistency in the MPA exposure-neutropenia relationship. We hypothesized that (i) adult de novo kidney transplant recipients who develop neutropenia have relatively higher dose-normalized MPA exposure than patients without neutropenia, and (ii) the observed neutropenia may be explained by polymorphisms in metabolism and/or transporter genes responsible for MPA disposition. METHODS: Adult kidney transplant recipients on steady-state tacrolimus and MPA, not receiving a corticosteroid, and with stable renal function were recruited for investigation at three periods post-transplant (1, 3, and 12 months; n = 21, 17, and 13, respectively). Clinical variables (age, weight, MPA daily dose, albumin, serum creatinine, absolute neutrophil count), tacrolimus and MPA concentrations (for exposure calculation), and genotypes (UGT2B7 G211T, UGT2B7 C802T, UGT1A9 T-275A, UGT1A9 T98C, MRP2 C-24T, MRP2 G1249A, OATP1B1 A388G, OATP1B1 C463A) were characterized. RESULTS: A significant inverse association between dose-normalized MPA exposure (a surrogate marker for apparent MPA clearance) and absolute neutrophil count in all three study periods (r2 ~ 0.3-0.7) was observed. No associations between characterized single nucleotide polymorphisms and MPA exposure or absolute neutrophil count were established. However, significant alterations in the minor allele frequencies of UGT2B7*2 C802T, UGT1A9 T275A, and MRP2 G1249A were evident. CONCLUSION: These findings support the clinical strategy for conducting MPA therapeutic drug monitoring in adult kidney transplant patients on steroid-free immunosuppressant therapy. The novel population genomic analysis data warrant further epidemiological investigations in a larger study sample.

Posttransplant Lymphoproliferative Disorder in Adults Receiving Kidney Transplantation in British Columbia: A Retrospective Cohort Analysis.

BACKGROUND: Posttransplant lymphoproliferative disorder (PTLD) is a major complication following kidney transplantation. OBJECTIVE: We undertook this study to characterize PTLD in kidney transplant patients in British Columbia with regard to incidence, patient and graft survival, histological subtypes, treatment modalities, and management of immunosuppression. DESIGN: Retrospective cohort analysis. SETTING: British Columbia. PATIENTS: All adult patients who underwent kidney transplantation in British Columbia between January 1, 1996, and December 31, 2012, were included. Patients less than 18 years of age at the time of first transplant and multiple organ transplant recipients were excluded from analysis. MEASUREMENTS: Patients with lymphoproliferative disorders that occurred subsequent to kidney transplantation were considered to have developed PTLD. METHODS: Cases of PTLD were identified by cross-referencing data abstracted from the provincial transplant agency's clinical database with the provincial cancer agency's lymphoma registry. Patients were followed up for the development of PTLD until December 31, 2012, and for outcomes of death and graft failure until December 31, 2014. Data collection was completed via an electronic chart review. RESULTS: Of 2217 kidney transplant recipients, 37 (1.7%) developed PTLD. Nine cases were early-onset PTLD, occurring within 1 year of transplant; of these cases, 6 were known/presumed Epstein-Barr virus mismatch, compared with only 2 of 28 late-onset cases. Patient survival for early-onset PTLD was 100% at 2 years post diagnosis. Late-onset PTLD had survival rates of 71.4% and 67.9% at 1 and 2 years, respectively. PTLD was associated with significantly decreased patient survival (P = .031) and graft survival (uncensored for death, P = .017), with median graft survival of PTLD and non-PTLD patients being 9.5 and 16 years, respectively. Immunosuppressant therapy was reduced in the majority of patients; additional therapies included rituximab monotherapy, CHOP-R, radiation, and surgery. LIMITATIONS: Limitations to this study include its retrospective nature and the unknown adherence of patients to prescribed immunosuppressant regimens. In addition, cumulative doses of immunosuppression received and the degree of immunosuppression reduction for PTLD management were not effectively captured. CONCLUSIONS: The incidence of PTLD in British Columbia following kidney transplantation was low and consistent with rates reported in the literature. The incidence of late-onset PTLD and its association with reduced patient and graft survival warrant further analysis of patients' long-term immunosuppression.

CONTEXTE: Le syndrome lymphoprolifératif post-greffe (SLPG) est une complication grave survenant à la suite d'une transplantation rénale. OBJECTIF DE L'ÉTUDE: Nous avons mené cette étude afin de caractériser le SLPG chez les receveurs d'une greffe rénale en Colombie-Britannique en ce qui a trait à son incidence, à la survie du patient et du greffon, aux sous-types histologiques, aux modalités de traitement et à la gestion de l'immunosuppression. CADRE ET TYPE D'ÉTUDE: Il s'agit d'une étude de cohorte rétrospective effectuée en Colombie-Britannique. SUJETS: Ont été inclus dans l'étude tous les patients adultes ayant subi une transplantation rénale entre le 1er janvier 1996 et le 31 décembre 2012 en Colombie-Britannique. Les patients âgés de moins de 18 ans au moment de l'intervention et les patients receveurs de greffe de multiples organes ont été exclus. MESURES: Tout cas de SL apparu après une greffe rénale étaient considérés comme un SLPG. MÉTHODOLOGIE: Les cas de SLPG ont été répertoriés en recoupant les données extraites de la base de données cliniques de l'agence provinciale de transplantation avec les données du registre des lymphomes tenu par l'agence provinciale de lutte contre le cancer. Les participants ont été suivis jusqu'au 31 décembre 2012 pour l'apparition du SLPG et jusqu'au 31 décembre 2014 pour les issues défavorables telles que la mort du patient ou le rejet du greffon. L'examen du dossier électronique des patients a complété la collecte des données. RÉSULTATS: Des 2 217 receveurs d'une greffe rénale répertoriés, seuls 37 (1,7 %) ont développé un SLPG. L'apparition du SLPG s'est faite de façon précoce, soit dans la première année post-greffe, pour neuf de ces patients, dont six représentaient un cas connu ou présumé de non-concordance pour le virus d'Epstein Barr (EBV). En comparaison, seuls deux des 28 patients ayant expérimenté un développement tardif du SLPG étaient présumés non-concordants pour l'EBV. Deux ans après le diagnostic, 100 % des patients ayant eu une apparition précoce du SLPG avaient survécu. Dans les cas de développement tardif de la maladie, le taux de survie passait à 71,4 % après un an et à 67,9 % après deux ans pour les patients. Le développement du SLPG a été associé avec une réduction significative de la chance de survie du patient (p = 0,031) et du greffon (p = 0,017, cas de décès non censurés). La survie médiane du greffon était de 9,5 ans pour les patients ayant développé un SLPG alors qu'elle était de 16 ans pour les autres. L'intensité du traitement immunosuppresseur a pu être réduite pour la majorité des patients. Les traitements additionnels incluaient la monothérapie au rituximab, le R-CHOP, la radiation et la chirurgie. LIMITES DE L'ÉTUDE: La nature rétrospective de l'étude est un facteur limitant la portée de nos résultats, de même que l'absence de données sur l'adhérence des patients au traitement immunosuppressif. De plus, nous n'avons pu mesurer précisément les doses cumulatives d'immunosuppresseurs reçues, ni le degré de réduction de ces derniers dans la prise en charge du SLPG. CONCLUSION: En Colombie-Britannique, l'incidence du SL post-greffe rénale s'est avérée faible et cohérente avec les taux rapportés dans la littérature. L'incidence de l'apparition tardive du SLPG et son association à un taux et une durée de survie amoindris (à la fois pour le patient et pour le greffon) justifient une analyse plus poussée de l'immunosuppression à long terme dans la population en question.

Evaluation of Collaborative Medication Reviews for High-Risk Older Adults.

BACKGROUND: Despite the widespread use of medication reviews, many older adults are still exposed to the risks of polypharmacy. OBJECTIVES: To quantify and describe the drug therapy problems identified and interventions undertaken by pharmacists before and after implementation (on July 1, 2015) of collaborative medication review for high-risk older adult patients (> 80 years of age). METHODS: A retrospective single-centre pre-post cohort study was conducted between July 1, 2014, and July 31, 2016, to characterize the impact of collaborative medication reviews-consisting of a thorough medication review by a pharmacist and care conferences with the hospitalist and family physician-on prescribing patterns in an Acute Care for Elders unit. A standardized template was used to conduct medication reviews for the post-implementation group, whereas a chart review was conducted for the pre-implementation group. The primary outcomes were the number of drug therapy problems identified by the clinical pharmacists and the associated interventions by the pharmacists, which were categorized as clinical or compliance interventions. Secondary outcomes included the number of medications at discharge, the rate of hospital readmission within 30 days, and the length of hospital stay. RESULTS: A total of 137 patients were identified for inclusion in either the pre-implementation group (n = 70) or the post-implementation group (n = 67). After implementation of collaborative medication reviews, there were statistically significant increases in the mean number of drug therapy problems identified (p < 0.001), the mean number of interventions undertaken (p = 0.004), and the median length of hospital stay (p < 0.001). There was no difference between the 2 groups in the number of medications at discharge, the proportion of patients taking more than 5 medications at discharge, or readmission within 30 days. CONCLUSION: At the study institution, implementation of a quality improvement program that included pharmacist-led medication reviews and collaborative care conferences involving community and hospital care providers helped to improve documentation by clinical pharmacists of potential medication-related problems and led to more interventions to optimize patients' medication regimens.

CONTEXTE: Malgré l'utilisation répandue des revues des médicaments, bon nombre de personnes âgées sont encore exposées à des risques causés par la polypharmacie. OBJECTIF: Quantifier et décrire les problèmes pharmacothérapeutiques repérés et les interventions effectuées par les pharmaciens avant et après la mise en place (le 1er juillet 2015) d'une revue collaborative des médicaments chez les patients âgés (de plus de 80 ans) à haut risque. MÉTHODES: Une étude de cohorte rétrospective avant-après menée dans un seul centre entre le 1er juillet 2014 et le 31 juillet 2016 dans le but d'offrir un portrait de l'influence des revues collaboratives des médicaments (qui se résument en une évaluation complète des médicaments par un pharmacien et des discussions sur les soins avec le médecin hospitalier et le médecin de famille) sur les habitudes de prescription dans une unité de soins de courte durée pour aînés. Un modèle standardisé a servi pour effectuer les revues des médicaments auprès du groupe d'après mise en place alors qu'une analyse des dossiers médicaux a été menée auprès du groupe d'avant mise en place. Les principaux critères d'évaluation étaient le nombre de problèmes pharmacothérapeutiques décelés par les pharmaciens cliniciens et les interventions connexes effectuées par les pharmaciens, qui ont été classées de type soit clinique soit conformité. Les critères d'évaluation secondaires comprenaient le nombre de médicaments au congé, les taux de réadmission dans les 30 jours suivant le congé et la durée du séjour à l'hôpital. RÉSULTATS: Au total, 137 patients répondaient aux critères d'admissibilité pour le groupe d'avant mise en place (n = 70) ou pour le groupe d'après mise en place (n = 67). Après la mise en place des revues collaboratives des médicaments, on a observé une augmentation statistiquement significative dans le nombre moyen de problèmes pharmacothérapeutiques décelés (p < 0,001), le nombre moyen d'interventions effectuées (p = 0,004) et la durée médiane du séjour à l'hôpital (p < 0,001). Aucune différence n'a été remarquée entre les deux groupes quant au nombre de médicaments au congé, à la proportion de patients prenant plus de cinq médicaments au congé et au taux de réadmission dans les 30 jours suivant le congé. CONCLUSION: À l'établissement où s'est déroulée l'étude, on a mis en place un programme d'amélioration de la qualité comprenant des revues des médicaments dirigées par des pharmaciens et des discussions sur les soins en collaboration avec des fournisseurs de soins communautaires et hospitaliers. Le programme a aidé à améliorer la consignation par les pharmaciens cliniciens de potentiels problèmes liés à la pharmacothérapie et a mené à un plus grand nombre d'interventions visant à optimiser la pharmacothérapie des patients.

Immunosuppression Practices in Liver Transplantation: A Survey of North American Centers.

OBJECTIVES: There is a clear lack of clinical evidence guiding immunosuppressive management in long-term stable liver transplant recipients. As a result, anecdotal experience suggests wide variability across transplant centers. We aimed to identify patterns of immunosuppression practices in liver transplant centers across Canada and the United States. MATERIALS AND METHODS: From February 9 to May 31, 2015, we invited clinicians from all liver transplant centers in Canada and the United States to answer a 6-question survey generated using SurveyMonkey. RESULTS: Seventeen respondents from 15 liver transplant centers completed the survey. Although immun-suppressive practices are relatively uniform for induction and early maintenance therapy, significant variations exist in the management of long-term immunosuppression in stable transplant recipients with a relative lack of minimization protocols. CONCLUSIONS: Our survey confirms a wide variability in immunosuppression practices across Canadian and US liver transplant centers. Research and practice priorities include design of pragmatic randomized controlled trials and development of clinical practice guidelines to standardize immunosuppressive management of long-term stable liver transplant recipients with a focus on immunosuppression minimization.

Interaction of Gender and Hepatitis C in Risk of Chronic Renal Failure After Liver Transplantation

ABSTRACT Background. Chronic renal failure (CRF) is a significant cause of morbidity and mortality in post-liver transplantation (LT) recipients. The risk factors associated with the development of renal dysfunction are not clearly elucidated. Objectives. To examine the risk factors in the development of CRF in these patients. Material and methods. Retrospective case-cohort of liver transplant patients without baseline kidney dysfunction who developed chronic renal failure during their follow-up. Results. Of 370 patients, 254 met the inclusion criteria. 30% (76) of these patients had CRF of which 57% (43) were male. Age, estimated glomerular filtration rate (eGFR) at discharge, and HCV infection were found to be risk factors for CRF post-LT. The odds ratio of developing CRF was 1.4 (0.6-3.3) in males with HCV, 1.6 (0.7-3.9) in females without HCV and 4.4 (1.5-13.2) among females with HCV when compared to men without HCV. Conclusions. In this cohort of LT receipients of a major Canadian city, age, eGFR, and HCV infection were risk factors for CRF. Female gender and HCV increased this odds by a factor of more than 4.

Interaction of Gender and Hepatitis C in Risk of Chronic Renal Failure After Liver Transplantation.

BACKGROUND: Chronic renal failure (CRF) is a significant cause of morbidity and mortality in post-liver transplantation (LT) recipients. The risk factors associated with the development of renal dysfunction are not clearly elucidated. OBJECTIVES: To examine the risk factors in the development of CRF in these patients. MATERIAL AND METHODS: Retrospective case-cohort of liver transplant patients without baseline kidney dysfunction who developed chronic renal failure during their follow-up. RESULTS: Of 370 patients, 254 met the inclusion criteria. 30% (76) of these patients had CRF of which 57% (43) were male. Age, estimated glomerular filtration rate (eGFR) at discharge, and HCV infection were found to be risk factors for CRF post-LT. The odds ratio of developing CRF was 1.4 (0.6-3.3) in males with HCV, 1.6 (0.7-3.9) in females without HCV and 4.4 (1.5-13.2) among females with HCV when compared to men without HCV. CONCLUSIONS: In this cohort of LT receipients of a major Canadian city, age, eGFR, and HCV infection were risk factors for CRF. Female gender and HCV increased this odds by a factor of more than 4.

A review of direct-acting antivirals for the treatment of hepatitis C in patients with advanced chronic kidney disease.

Historically, standard treatment of hepatitis C virus (HCV) infection in patients with renal impairment has been limited by low cure rates and poor tolerability. The introduction of direct-acting antivirals (DAAs) has revolutionized the treatment of HCV with impressive cure rates >90% and low rates of adverse events. Despite these major advancements, treatment of patients with HCV and advanced chronic kidney disease (CKD) is a major challenge due to the lack of efficacy and safety data in this patient population. The purpose of this review is to summarize the available data for efficacy and safety of the following DAAs in treating HCV patients with advanced Stage 4 and 5 CKD: simeprevir, sofosbuvir, ledipasvir, ombitasvir, paritaprevir, dasabuvir, grazoprevir, elbasvir and daclatasvir.

Response to Sildenafil in a Patient With Coexisting Post-Liver Transplant Portopulmonary Hypertension and Hepatopulmonary Syndrome.

Hepatopulmonary syndrome and portopulmonary hypertension are complications of portal hypertension with opposing mechanisms that can coexist. Moderate portopulmonary hypertension, which is a contraindication to a liver transplant, must be managed with pulmonary vasodilators to normalize pulmonary arterial pressures before a transplant listing. Concomitant hepatopulmonary syndrome complicates the management of portopulmonary hypertension, as pulmonary vasodilators can theoretically exacerbate the intrapulmonary dilatation believed to cause hepatopulmonary syndrome. We describe a case of a post-liver transplant patient with concomitant hepatopulmonary syndrome and portopulmonary hypertension safely treated with sildenafil.

Ursodeoxycholic Acid in Treatment of Non-cholestatic Liver Diseases: A Systematic Review.

Aims: To systematically evaluate the literature for evidence to support the use of bile acids in non-cholestatic liver conditions. Methods: Searches were conducted on the databases of Medline (1948-March 31, 2015), Embase (1980-March 31, 2015) and the Cochrane Central Register of Controlled Trials, and on Google and Google Scholar to identify articles describing ursodeoxycholic acid (UDCA) and its derivatives for non-cholestatic hepatic indications. Combinations of the following search terms were used: ursodeoxycholic acid, ursodiol, bile acids and/or salts, non alcoholic fatty liver, non alcoholic steatohepatitis, fatty liver, alcoholic hepatitis, alcohol, liver disease, autoimmune, autoimmune hepatitis, liver transplant, liver graft, transplant rejection, graft rejection, ischemic reperfusion injury, reperfusion injury, hepatitis B, hepatitis C, viral hepatitis, chronic hepatitis, acute hepatitis, transaminases, alanine transaminase, liver enzymes, aspartate aminotransferase, gamma-glutamyl transferase, gamma-glutamyl transpeptidase, bilirubin, alkaline phosphatase. No search limits were applied. Additionally, references of the included studies were reviewed to identify additional articles. Results: The literature search yielded articles meeting inclusion criteria for the following indications: non-alcoholic fatty liver disease (n = 5); alcoholic liver disease (n = 2); autoimmune hepatitis (n = 6), liver transplant (n = 2) and viral hepatitis (n = 9). Bile acid use was associated with improved normalization of liver biochemistry in non-alcoholic fatty liver disease, autoimmune hepatitis and hepatitis B and C infections. In contrast, liver biochemistry normalization was inconsistent in alcoholic liver disease and liver transplantation. The majority of studies reviewed showed that normalization of liver biochemistry did not correlate to improvement in histologic disease. In the prospective trials reviewed, adverse effects associated with the bile acids were limited to minor gastrointestinal complaints (most often, diarrhea) and did not occur at increased frequency as compared to controls. As administration of bile acids was often limited to durations of 12 months or less, long-term side effects for non-cholestatic indications cannot be excluded. Conclusions: Based on the available literature, bile acids cannot be widely recommended for non-cholestatic liver diseases at present.

Successful Treatment of Hepatitis C with Simeprevir, Sofosbuvir, and Ribavirin in an HIV Coinfected Liver Transplant Patient with Advanced Chronic Kidney Disease.

Although major advances have occurred in treating patients with hepatitis C virus (HCV) with the development of new direct-acting antivirals (DAAs), treatment of liver transplant recipients with HCV, human immunodeficiency virus (HIV) coinfection, and renal disease is challenging due to the lack of efficacy and safety data in this population. We report a case of successful HCV therapy in a postliver transplant HIV coinfected patient, with stage 4 chronic kidney disease, using an all-oral regimen of simeprevir, sofosbuvir, and ribavirin. The 51-year-old male achieved SVR24, and no specific HIV-related or transplant-related adverse events were documented during the treatment period. The new DAAs show promise for HIV coinfected patients and those with severe to end-stage renal disease (ESRD); however, robust clinical trials or large cohort studies will need to be conducted to confirm the efficacy and safety of these newer agents in this setting.

Drug Interactions With Direct-Acting Antivirals for Hepatitis C: Implications for HIV and Transplant Patients.

OBJECTIVE: Review pharmacokinetics of new direct-acting antivirals (DAAs) for hepatitis C (HCV) infection and interactions with concomitant immunosuppressant and antiretroviral therapies (ART). DATA SOURCES: MEDLINE (1948-January 2015), EMBASE (1964-January 2015), International Pharmaceutical Abstracts (1970-January 2015), Google, and Google Scholar were searched combining the terms simeprevir, sofosbuvir, ledipasvir, daclatasvir, paritaprevir, ABT-450, ombitasvir, dasabuvir, pharmacokinetics, drug interaction, drug metabolism, HIV, antiretroviral, immunosuppressant, transplant. Articles, conference proceedings, abstracts, and product monographs were reviewed. STUDY SELECTION AND DATA EXTRACTION: Literature on pharmacokinetic or pharmacodynamic interactions with DAAs and immunosuppressants or ART was considered for inclusion. Pertinent information was extracted and summarized in the review. In the absence of data, pharmacokinetic and pharmacodynamic principles were used to predict the likelihood of interactions. DATA SYNTHESIS: DAA pharmacokinetics are reviewed and drug interaction data are presented with provision of management strategies. Fixed-dose combination paritaprevir/ritonavir/ombitasvir plus dasabuvir is most susceptible to drug interactions with immunosuppressants and ART mainly due to the influence of ritonavir on multiple enzymes. Simeprevir is also prone to drug interactions because of cytochrome P450(CYP) 3A4, CYP1A2, P-glycoprotein, and OATP1 involvement and is not recommended for use in combination with several HIV antiretrovirals (ARVs). Close therapeutic drug monitoring of calcineurin inhibitors is required with concomitant simeprevir. Few clinically significant interactions are expected with sofosbuvir or ledipasvir. Limited data suggest that daclatasvir may be coadministered with immunosuppressants but requires dose adjustments with certain ARVs. CONCLUSIONS: None of the DAAs are completely free of drug interactions. Awareness and management of drug interactions is critical to optimize outcomes and minimize adverse effects in these patient populations.

Assessing medication adherence in solid-organ transplant recipients.

OBJECTIVES: We sought to determine and compare the prevalence of nonadherence in lung, kidney, and liver transplant recipients, and identify potential risk factors for nonadherence. MATERIALS AND METHODS: This cross-sectional, single-center, retrospective cohort study, evaluated 225 outpatient lung, kidney, and liver transplant recipients' adherence to immunosuppressant medication. Based on immunosuppressant dosages and dispensing records, medication possession ratio (days of medication supplied/actual days) and gaps in prescription refills (> 30-day lapse between expected depletion of supply and next refill) were used as surrogate markers in assessing adherence for 2 years. Patients were adherent to their immunosuppressant medication regimens if their medication possession ratio was ≥ 80%. RESULTS: The mean age of the subjects was slightly greater than 50 years of age, and they were a median of 2.0, 1.3, and 1.1 years posttransplant at the start of data collection for lung, kidney, and liver recipients. Overall medication possession ratios were 95.4% ± 7.5%, 95.9% ± 7.6%, and 92.7% ± 12.3% in our lung, kidney, and liver recipients. Only 7.1% of patients had a medication possession ratio lower than 80%, which was the cutoff for nonadherence. No statistical analyses were performed to identify potential factors for nonadherence because of the small number of nonadherent patients. CONCLUSIONS: Immunosuppressant medication adherence at our center was high for all 3 organ cohorts, as measured by a medication possession ratio of 80% or better. Further study is needed to evaluate immunosuppressant adherence over time after transplant, and confirm the clinical factors that optimize adherence in high-risk patients.

Review of boceprevir and telaprevir for the treatment of chronic hepatitis C.

OBJECTIVE: To summarize and evaluate the published literature pertaining to boceprevir and telaprevir, and to provide clinicians with suggestions for use in patients with chronic hepatitis C infection. METHODS: A standardized search strategy was performed using the MEDLINE, EMBASE, Google Scholar and International Pharmaceuticals Abstracts databases using the search terms "boceprevir", "telaprevir", "boceprevir and hepatitis C", and "telaprevir and hepatitis C". A manual search of references was performed to identify articles missed by the electronic search. Studies were included in the review if they assessed either boceprevir or telaprevir in comparison with standard of care in chronic hepatitis C patients. RESULTS: The studies identified assessed boceprevir and telaprevir in genotype-1 hepatitis C patients. In both treatment-naive and treatment-experienced patients, sustained virological response rates were achieved more often with boceprevir or telaprevir in combination with pegylated interferon and ribavirin compared with pegylated interferon and ribavirin alone. Both medications were well tolerated, with anemia presenting as the most treatment-limiting adverse effect. CONCLUSIONS: Boceprevir and telaprevir will revolutionize the management of hepatitis C genotype 1 patients and will most likely decrease the burden of end-stage disease worldwide. However, current clinical limitations include establishing appropriate and cost-effective treatment durations, and use in special populations such as transplant patients and patients coinfected with HIV. Future research will need to clarify these clinical obstacles to clearly define the role of these agents in hepatitis C management.