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.

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.

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.

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.

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.

A review of drug interactions with boceprevir and telaprevir: implications for HIV and transplant patients.

PURPOSE: Chronic hepatitis C virus (HCV) is a major problem affecting up to 170 million people worldwide. Two protease inhibitors have recently been approved that will revolutionize treatment. Our objective was to summarize and evaluate the literature pertaining to the pharmacokinetics of boceprevir and telaprevir, in order to provide clinicians with insight into the management of actual and potential drug interactions. SUMMARY: A standardized search using MEDLINE (1948-November 2011), EMBASE (1980-November 2011), IPA (1970-November 2011), Google, and Google Scholar that combined the search terms boceprevir, telaprevir, pharmacokinetics, drug interaction, and drug metabolism was performed. Manual reference searches of chosen articles were completed. Monographs and articles, conference proceedings, and abstracts were evaluated. Boceprevir and telaprevir are both substrates and inhibitors of cytochrome P450 3A4 and telaprevir is a substrate of p-glycoprotein. Levels of boceprevir are decreased in patients taking efavirenz but effects with other antiretrovirals are minimal or unknown. Coadministration with efavirenz may compromise telaprevir levels and should be avoided. Telaprevir may increase levels of cyclosporine, tacrolimus, atorvastatin, and amlodipine, which may expose patients to increased adverse effects. Conclusions. Significant drug-drug interactions occur with both boceprevir and telaprevir. Until studies are reported and experience is gained with these agents, clinicians will need to be careful when administering in high-risk populations and those receiving chronic therapy with interacting agents. Studies are urgently needed in HIV patients taking antiretrovirals and patients taking chronic immunosuppression as these populations are at increased risk of experiencing clinically significant interactions.

Development and validation of limited sampling strategies for tacrolimus and mycophenolate in steroid-free renal transplant regimens.

PURPOSE: 1) To develop and validate limited sampling strategies (LSSs) for tacrolimus (TAC) and mycophenolic acid (MPA) in renal transplant recipients not receiving corticosteroids; and 2) to evaluate predictive performance of published LSSs (for steroid-based regimens) in a steroid-free population. METHODS: On administration of steady-state morning TAC and mycophenolate mofetil doses, 12-hour serial blood samples from 28 stable renal transplant recipients were collected and measured by validated high-performance liquid chromatography methods and area under the curve (AUC) by trapezoidal rule. TAC LSSs were developed and validated by multiple regression analysis by a two-group method (index n = 18; validation n = 10) and MPA LSSs by the jackknife method (n = 28). Potential LSSs were those with r ≥ .8 (TAC) or r ≥ 0.7 (MPA) and < 3 time points within 2 hours (TAC) or 4 hours (MPA) postdose. Predictive performance was calculated and other published TAC and MPA LSSs tested using preset criteria for bias and precision of within ± 15%. RESULTS: For TAC, three three-concentration, one two-concentration, and one one-concentration model met preset criteria. The best equations were: TAC AUC = 10.338 + 7.739C0 + 3.589C2 (r = 0.956, bias = -3.4%, precision = 4.7%) and TAC AUC = 29.479 + 5.016C2 (r = 0.862, bias = 3.2%, precision = 9.7%). For MPA, only one model was identified: MPA AUC = 9.328 + 1.311C1 + 1.455C2 + 2.901C4 (r = 0.838, bias = -3.8%, precision = 14.9%). One published TAC (and no MPA) LSS in renal transplant recipients on steroid-based regimens met criteria. CONCLUSIONS: To the authors' knowledge, these LSSs are the first to be developed and validated in steroid-free renal transplant recipients and can be used to accurately predict TAC and MPA AUCs for steroid-free regimens. Because the commonly used MPA LSS is based on a steroid regimen and not predictive for steroid-free patients, the newly derived MPA LSS is being applied at the authors' institution. Other renal transplant centers may also wish to validate this equation in their own patients.

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.

Pharmacokinetics of mycophenolic acid and its glucuronidated metabolites in stable islet transplant recipients.

Given the paucity of data on pharmacokinetics of mycophenolic acid (MPA) in islet transplant, the aim of this study was to characterize pharmacokinetic parameters of MPA and its 2 glucuronidated metabolites in stable islet transplant recipients. Sixteen subjects were entered into this open-label study after written informed consent. Upon administration of a steady-state morning mycophenolate mofetil dose, 12-hour serial concentrations of MPA and its phenolic glucuronide (MPAG) and acyl-glucuronide (AcMPAG) were measured by a validated high-performance liquid chromatography method and pharmacokinetic parameters analyzed by noncompartmental modeling. Subjects included 11 women and 5 men who had received 2.7 +/- 0.8 islet transplants. Age was 50 +/- 8 years, weight 64 +/- 11 kg, serum albumin 4.2 +/- 0.3 g/dL, and serum creatinine 1.1 +/- 0.4 mg/dL. All patients were also on tacrolimus-based steroid-free immunosuppressant regimens. Mycophenolate mofetil dosage ranged from 1 to 2 g daily (25.4 +/- 6.1 mg/kg/d). Pharmacokinetic parameters for MPA were area under the curve 42.9 +/- 21.6 microg h/mL; dose-normalized AUC 52.9 +/- 25.4 microg h/mL/g; maximal concentration (Cmax) 13.0 +/- 6.2 microg/mL; time to Cmax (tmax) 1.2 +/- 0.4 hours; minimum concentration (Cmin) 1.4 +/- 1.0 microg/mL; and MPA-free fraction 1.2% +/- 1.0%. Area under the curve ratios of MPAG/MPA and AcMPAG/MPA were 17.8 +/- 12.4 and 0.1 +/- 0.1, respectively. The wide interpatient variability in all pharmacokinetic parameters of MPA and metabolites are consistent with results from the only other published pharmacokinetic study in islet transplant recipients. A population model and a search for significant covariates may help reduce this variability. Pharmacokinetic parameters calculated in the present study, coupled with findings from the only other published MPA study in islet transplant, form a preliminary base on which to build a population model for future multicenter studies of this little-studied transplant subpopulation.

Limited sampling strategies for predicting area under the concentration-time curve of mycophenolic acid in islet transplant recipients.

BACKGROUND: Mycophenolate mofetil is widely used in islet transplant recipients and its active metabolite, mycophenolic acid (MPA), exhibits wide pharmacokinetic variability. However, to our knowledge, no limited sampling strategy (LSS) exists for monitoring MPA in this subpopulation. OBJECTIVE: To define optimal LSSs for MPA monitoring and to test their predictive performance in islet transplant recipients. METHODS: After written informed consent was obtained and upon administration of a steady-state morning mycophenolate mofetil dose, blood samples were collected at 0, 0.3, 0.6, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours from 16 stable islet transplant recipients. MPA concentrations were measured by a validated high-performance liquid chromatography method with ultraviolet detection and pharmacokinetic parameters analyzed by noncompartmental modeling. All 16 patients' profiles were used to develop the LSSs via multiple regression analysis. Potential LSSs were restricted to ones having R(2) 0.90 or greater and 3 or fewer time points within the first 4 hours postdose. Resulting equations were validated for their predictive performance using the jackknife method, with acceptable criteria for bias and precision preset to within +/-15%. In addition, 14 published LSSs (in the renal transplant population) were tested in our islet transplant patients. RESULTS: Five LSSs met preset criteria and had conventional sampling times: AUC = 1.783 + 1.248C1 + 0.888C2 + 8.027C4 (R2 = 0.98, bias = -3.09%, precision = 9.53%) AUC = 2.778 + 1.413C1 + 0.963C3 + 7.511C4 (R2 = 0.97, bias = -3.22%, precision = 11.02%) AUC = 1.448 + 1.239C1 + 0.271C1.5 + 9.108 C4 (R2 = 0.96, bias = -1.90%, precision = 11.46) AUC = 1.410 - 0.259C0 + 1.443C1 + 9.622C4 (R2 = 0.96, bias = -2.68%, precision = 11.53%) AUC = 1.547 + 1.417C1 + 9.448C4 (R2 = 0.96, bias = -2.46%, precision = 11.14%) where AUC = area under the concentration-time curve. None of the other published LSSs in the renal transplant population met the preset criteria for bias and precision. CONCLUSIONS: To our knowledge, these are the first precise and accurate LSSs for predicting MPA AUC developed specifically for islet transplant recipients. The LSS that we recommend is the one utilizing 2 concentrations: AUC = 1.547 + 1.417C1 + 9.448C4. This equation is convenient and clinically feasible. Other islet transplant centers may wish to validate our equation in their population or use our template as a guide to develop accurate and precise LSSs specific to their patient population.

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.

The utility of therapeutic drug monitoring for ribavirin in patients with chronic hepatitis C--a critical review.

OBJECTIVE: To evaluate the utility of therapeutic drug monitoring (TDM) for ribavirin in chronic hepatitis C. DATA SOURCES: Literature searches were conducted through PubMed (1949-June 2009), EMBASE (1980-June 2009), BIOSIS Previews (1969-June 2009), International Pharmaceutical Abstracts (1970-June 2009), Google, and www.clinicaltrials.gov using the terms ribavirin, therapeutic monitoring, hepatitis C, and drug levels. In addition, pertinent reference citations from identified publications were reviewed. Studies were limited to English language, adult age, and human subjects. STUDY SELECTION AND DATA EXTRACTION: All articles identified from the data sources were evaluated. Studies that measured ribavirin concentrations or dose and treatment response were included in the review. DATA SYNTHESIS: While monitoring of ribavirin plasma concentrations to improve treatment response in patients with chronic hepatitis C has been described in the literature, the utility of TDM for ribavirin in this group of patients has not been systematically studied. Thus, a previously published 9-step decision-making algorithm was employed to help determine whether TDM is warranted, based on currently available evidence. Thirty articles involving patients with chronic hepatitis C mono-infection, 12 for hepatitis C-HIV coinfection, 5 for renal dysfunction, and 5 for post-liver transplant patients were reviewed. In all subpopulations, studies exist that either support or refute the usefulness of ribavirin TDM. Additionally, the majority of the included studies had methodologic limitations, such as small sample size, retrospective analyses, and lack of p value adjustment for multiple analyses. Large randomized controlled trials would help to definitively answer this question. CONCLUSIONS: There is conflicting evidence about the existence of a correlation between ribavirin concentrations and virologic response or development of toxicity. This inconsistent evidence, coupled with the currently employed effective strategies that maximize sustained virologic response and minimize development of anemia, precludes the utility of TDM for ribavirin.

Iron overload disorders: treatment options for patients refractory to or intolerant of phlebotomy.

Iron overload disorders involve excess accumulation of iron in body tissues as a result of hereditary and nonhereditary diseases. If left untreated, tissue iron deposition can result in organ damage. Treatment options such as phlebotomy, chelating agents, and erythrocytapheresis can prevent complications and target organ damage. Although phlebotomy is the gold standard for iron overload treatment in the setting of hereditary hemochromatosis, this procedure is usually not feasible for other iron overload conditions, especially those associated with anemia. With the introduction of newer, oral chelating agents, more options are available for patients refractory to or intolerant of parenteral chelating agents.

Corticosteroid interactions with cyclosporine, tacrolimus, mycophenolate, and sirolimus: fact or fiction?

OBJECTIVE: To review the current clinical evidence on the effects of corticosteroid interactions with the immunosuppressive drugs cyclosporine, tacrolimus, mycophenolate, and sirolimus. DATA SOURCES: Articles were retrieved through MEDLINE (1966-February 2008) using the terms corticosteroids, glucocorticoids, immunosuppressants, cyclosporine, tacrolimus, mycophenolate, sirolimus, drug interactions, CYP3A4, P-glycoprotein, and UDP-glucuronosyltransferases. Bibliographies were manually searched for additional relevant articles. STUDY SELECTION AND DATA EXTRACTION: All English-language studies dealing with drug interactions between corticosteroids and cyclosporine, tacrolimus, mycophenolate, and sirolimus were reviewed. DATA SYNTHESIS: Corticosteroids share common metabolic and transporter pathways, the cytochrome P450 and P-glycoprotein (P-gp/ABCB1) systems, respectively, with cyclosporine, tacrolimus, and sirolimus. As a group, corticosteroids induce the CYP3A4 and P-gp pathways; however, a few exceptions exist and the impact on a patient's immunosuppressant regimen may be critical. Corticosteroids also have demonstrated an induction effect on the uridine diphosphate-glucuronosyltransferase enzymes and multidrug resistance-associated protein 2 involved in mycophenolate's disposition. Successful corticosteroid withdrawal regimens have been reported; however, only few studies have examined the effects of steroid withdrawal on the remaining immunosuppressive regimens. To date, the clinical impact of steroid withdrawal on disposition of other immunosuppressive agents is not well characterized, and reports of such drug-drug interactions are conflicting. CONCLUSIONS: While our understanding of the clinical impact of steroid-immunosuppressant interactions is limited, it remains a fact that corticosteroids have complex induction and inhibition interactions with common metabolic and transport pathways. Given the complex interaction of corticosteroids on crucial metabolic enzymes and transporter proteins, monitoring of immunosuppressive agents during steroid withdrawal is warranted to ensure optimal treatment outcomes.

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.

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.