Effects of Transportation of IV Bags Containing Protein Formulations Via Hospital Pneumatic Tube System: Particle Characterization by Multiple Methods.

In hospitals, often drug products in intravenous (IV) bags are transported via pneumatic tube systems (PTS). The goal of this study was to evaluate the effects of such transportation of protein products on particle formation in polyvinyl chloride (PVC) and polyolefin (PO) IV bags, containing either IV saline or dextrose. We studied intravenous immunoglobulin (IVIG) and a monoclonal antibody (mAb). Particles were quantified with flow imaging, light obscuration and nanoparticle tracking analysis. PTS transportation of IVIG caused large increases in protein particle concentrations, with much greater increases observed in saline than in dextrose. The increases were greater in IV solutions in PO than those in PVC bags. With the mAb, PTS transportation in saline caused increases in protein particle levels in PO bags, but not in PVC bags. Transportation in dextrose did not result in significant increases in mAb particle concentrations in IV bags made of either material. Overall, the results document that the PTS transportation can result in large increases in protein particles and that magnitude of these increases depends the protein itself, the bag material and the IV solution. The main conclusion is that protein products in IV solutions should not be transported in hospital PTS.

Transthyretin Amyloid Cardiomyopathy-Current and Future Therapies.

OBJECTIVE: To describe the clinical presentation of transthyretin amyloid cardiomyopathy (ATTR-CM) and discuss current treatments and investigational products and their effect on patient outcomes. DATA SOURCES: A literature search was performed in PubMed (September 2018 to December 2020) using the following keywords: transthyretin amyloidosis, cardiomyopathy, polyneuropathy and transthyretin amyloid cardiomyopathy, monoclonal light-chain, tafamidis, cardiac amyloidosis, ATTR cardiomyopathy, green tea and inhibition of cardiac amyloidosis, AG10, tolcapone, tolcapone and leptomeningeal ATTR, PRX004, NI006, patisiran, inotersen, vutrisiran, AKCEA-TTR-LRx, and NTLA-2001. STUDY SELECTION AND DATA EXTRACTION: Clinical trials were evaluated for evidence supporting pharmacology, safety, efficacy, and measured outcomes. DATA SYNTHESIS: Until 2019, there were no approved treatments for ATTR-CM. Treatment consisted of symptom management and organ transplant. Nonpharmacological and pharmacological treatments focused on the symptoms of heart failure (HF) associated with ATTR-CM. However, there are several emerging therapies recently approved or in development to address the underlying pathophysiology. Treatment classes for ATTR-CM include transthyretin stabilizers, human monoclonal antibodies, gene silencers, and CRISPR/Cas9 gene editing. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: ATTR-CM is a complex disease in which amyloidosis causes cardiomyopathy. Underdiagnosis is attributed to the clinical presentation being heterogeneous, indistinguishable from HF caused by other etiologies, and the need for invasive testing modalities, including endomyocardial biopsy. Improved diagnostic approaches along with targeted therapies can slow disease progression and enhance patient quality of life. CONCLUSION: Diagnostic modalities along with biomarker and genetic testing could detect disease earlier and target therapy more accurately. Novel therapies demonstrate potential treatment benefits and can help shape the standard of care for these patients.

Feasibility of ASsisTed WARfarin Dosing by Clinical Pharmacy Support Assistants (FAST-WARD Study).

BACKGROUND: Pharmacy-managed warfarin dosing has been established at Burnaby Hospital, in Burnaby, British Columbia, for over 10 years. With increases in the number and acuity of patients enrolled, it has become challenging to maintain a successful anticoagulation program. The clinical pharmacy support assistant (CPSA) program was initiated to support the provision of clinical pharmacy services. At the time of the study, Burnaby Hospital had 2 CPSAs. It was anticipated that the pharmacy-managed inpatient warfarin dosing service might benefit from support through the CPSA program to maintain a consistent level of delivery. OBJECTIVE: To examine the feasibility of CPSAs supporting the pharmacy-managed inpatient warfarin dosing service at Burnaby Hospital. Feasibility was based on 4 key parameters: knowledge base, accuracy of data collection, dosage recommendations, and time spent on the process. METHODS: An observational, prospective pilot study was conducted over 3 months. The CPSAs were given appropriate education and training, and their performance was assessed to determine the feasibility of CPSA-assisted warfarin dosing. The CPSAs had to achieve a priori target scores for each of the 4 parameters in order for CPSA-assisted warfarin dosing to be considered feasible. RESULTS: After the didactic sections, both CPSAs answered all review questions correctly. The accuracy of data collection (based on 60 patient encounters) was 98.3%. The warfarin regimens recommended by the CPSAs were similar to those recommended by the clinical pharmacists, with doses differing by a mean of 0.46 mg. For 39 (65%) of the 60 patient encounters, the dosing recommendations of CPSAs and clinical pharmacists were identical. The average time spent per patient encounter was 10.5 min. CONCLUSION: With appropriate training and education, it is feasible for CPSAs to support the pharmacy-managed inpatient warfarin dosing program at Burnaby Hospital.

CONTEXTE: Un programme d'ajustement posologique de la warfarine géré par le pharmacien est en place à l'hôpital Burnaby depuis plus de 10 ans. Comme le nombre de patients inscrits au programme s'accroît et que la gravité des cas augmente, il est maintenant difficile pour le programme d'anticoagulothérapie de conserver le même niveau de performance. Le programme d'assistant au soutien de la pharmacie clinique (ASPC) a été mis en place dans le but de soutenir la prestation de services de pharmacie clinique. Au moment de l'étude, l'hôpital Burnaby avait deux ASPC. Le service d'ajustement par le pharmacien de la posologie de la warfarine des patients hospitalisés pourrait bénéficier du soutien du programme d'ASPC afin de conserver un niveau de prestation uniforme. OBJECTIF: Étudier la possibilité pour les ASPC de soutenir le service d'ajustement par le pharmacien de la posologie de la warfarine des patients hospitalisés offert par l'hôpital Burnaby. La faisabilité était fondée sur quatre paramètres clés : la base de connaissances, l'exactitude de la collecte de données, les recommandations posologiques et le temps alloué au processus. MÉTHODES: Une étude pilote prospective observationnelle a été menée sur une période de trois mois. Les ASPC ont obtenu un enseignement et une formation adéquate et, suite à cela, leur travail a été évalué dans le but de déterminer si une aide à l'ajustement posologique de la warfarine est possible. Les ASPC devaient atteindre des scores prédéfinis a priori pour chacun des quatre paramètres pour que leur aide à l'ajustement posologique de la warfarine soit considérée comme faisable. RÉSULTATS: Après avoir participé aux volets didactiques, les deux ASPC ont répondu correctement à l'ensemble des questions d'évaluation. L'exactitude de la collecte de données (fondée sur 60 rencontres avec des patients) était de 98,3 %. Les schémas posologiques de warfarine recommandés par les assistants étaient semblables à ceux recommandés par les pharmaciens cliniciens et variaient en moyenne de 0,46 mg. Pour 39 (65 %) des 60 rencontres avec des patients, les recommandations posologiques des assistants étaient identiques à celles des pharmaciens cliniciens. Chaque rencontre durait en moyenne 10,5 minutes. CONCLUSION: À l'aide d'une formation et d'un enseignement adéquats, il est donc possible pour les ASPC de soutenir le programme d'ajustement par le pharmacien de la posologie de la warfarine des patients hospitalisés offert par l'hôpital Burnaby. [Traduction par l'éditeur].

Analysis of Orders for QTc-Prolonging Medication for Intensive and Cardiac Care Unit Patients with Pre-existing QTc Prolongation (QTIPPP Study).

BACKGROUND: A prolonged QTc interval on electrocardiography is often used as a surrogate marker for ventricular arrhythmia. Medications that can prolong the QTc interval may increase the risk of cardiac complications, although the exact incidence is unknown. It is reasonable to assume that administration of QTc-prolonging medications to patients with pre-existing QTc prolongation will further increase the risk of cardiac consequences. This study was designed to examine the frequency of prescription of QTc-prolonging medications in such patients and to explore the potential for clinical pharmacists to minimize the associated risks. OBJECTIVES: The primary objective was to identify the number of patients with pre-existing prolonged QTc interval for whom QTc-prolonging medications were prescribed, from among all patients with orders for QTc-prolonging medications. The secondary objectives were to determine patterns of intervention by clinical pharmacists in these cases and to document any further QTc prolongation and occurrence of cardiac events. METHODS: A prospective, observational, quality assessment study was conducted over 4.5 months. Adult patients admitted to beds with cardiac monitoring by telemetry for whom one or more QTc-prolonging medications were ordered were eligible for inclusion. Patients were included if the QTc interval was longer than 450 ms on the most recent 12-lead electrocardiogram before the QTc-prolonging medication was ordered. These patients were followed to identify outcomes of interest after administration of QTc-prolonging medication. RESULTS: Overall, a QTc-prolonging medication was prescribed for 207 patients. Of these, 53 patients (26%) had pre-existing prolongation of the QTc interval. Clinical pharmacists made recommendations related to 28 medication orders; of these, 16 (57%) were accepted by the physician. Fifty-one (96%) of the 53 patients received at least one dose of QTc-prolonging medication and were monitored daily for complications. Nine (18%) of the 51 patients who underwent daily monitoring experienced at least one cardiac event. CONCLUSIONS: A substantial proportion (26%) of patients for whom QTc-prolonging medications were prescribed had pre-existing prolongation of the QTc interval. Clinical pharmacists may have a role in reducing the risk of subsequent complications.

Assessing lipid lowering and plasma cholesteryl ester transfer protein activity of simvastatin following administration to rabbits fed a high fat/cholesterol diet.

PURPOSE: The purpose of this study was to assess the lipid lowering and plasma cholesteryl ester transfer protein (CETP) activity following administration of simvastatin to rabbits fed a high fat/cholesterol diet. METHODS: Male New Zealand white rabbits were housed in individual cages and fed a standard diet for 7 days. After 7 days, animals were fed 10 g of a regular chow diet plus 100 g of the same diet supplemented with 0.5% (w/v) cholesterol and 14.0% (w/v) coconut oil for 28 days. Following 28 days on this diet, the animals were randomized based on plasma cholesterol and triglyceride levels, into a group of control animals and a group (n = 6) of animals fed 100 g of cholesterol/coconut diet plus 10 g regular chow diet containing simvastatin (3 mg/kg/day) for an additional 28 days. Blood samples were taken from the marginal ear vein prior to and 28 days after the initiation of drug treatment. Plasma was harvested and stored at 4 degrees C prior to lipid analysis. Plasma total cholesterol and triglyceride levels were quantified using enzymatic kits. HDL (high-density lipoproteins) cholesterol levels were determined using the dextran sulfate-Mg(2+) precipitation method. ApoB cholesterol levels were determined by subtracting total cholesterol from HDL cholesterol. Cholesteryl ester transfer protein (CETP) activity was determined by standard assay methods. RESULTS: We observed that simvastatin significantly reduced total plasma cholesterol, triglyceride, and apoB cholesterol compared to non-treated controls. Simvastatin treatment did not alter serum CETP activity compared to non-treated controls. CONCLUSIONS: These findings suggest that decreasing plasma lipid levels by treatment with simvastatin is not due to changes in serum CETP activity in rabbits fed a high fat/cholesterol diet.