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Neville H.L.,Street Capital | Chevalier B.,Street Capital | Daley C.,Multi Organ Transplant Program | Nodwell L.,Street Capital | And 6 more authors.
International Journal of Pharmacy Practice | Year: 2014

Objective Clinical pharmacists improve the quality of patient care by reducing adverse drug events (ADEs), length of stay and mortality. This impact is currently not well described in surgery. The objective was to evaluate clinical and economic outcomes after clinical pharmacist services were added to two general surgical wards in an adult hospital. Methods This was a prospective, observational study. All clinical interventions to resolve drug therapy problems were documented and assessed for severity, value and the probability of preventing an ADE. Cost avoidance was calculated using two methods: by avoiding additional days in hospital (CA$3593/ADE) or additional hospital costs ($7215/ADE). Two clinical pharmacy specialists and the surgical care pharmacist independently categorized the interventions; disagreements were resolved by consensus. Key findings The pharmacists made 1097 interventions in 6 months with a 98% acceptance rate by surgical staff. Half of the interventions were rated significant for severity (561, 51.1%) and value (559, 51.0%). One-quarter of the interventions had a 40% or greater probability of preventing an ADE (270, 24.6%). Cost avoidance was estimated to be $0.68-1.36 million or $617-1239 per intervention. Pharmacists avoided an additional 867 days in the hospital for surgical patients. Conclusion The pharmacist's role in the management of the drug therapy needs of the post-surgical patient has the potential to improve clinical and patient outcomes and avoid healthcare costs. The inclusion of clinical pharmacists in surgical wards may result in $7 in savings for every $1 invested. © 2013 Royal Pharmaceutical Society.

Kiberd B.A.,Dalhousie University | Lawen J.,Multi Organ Transplant Program | Lawen J.,Dalhousie University | Daley C.,Multi Organ Transplant Program
Therapeutic Drug Monitoring | Year: 2012

BACKGROUND: Studies have shown that achieving adequate exposure of mycophenolic acid (MPA) early post transplant is associated with less acute rejection in kidney recipients. Intensified dosing with the equivalent of mycophenolate mofetil (MMF) 3 g daily in tacrolimus-treated patients has been shown to increase exposure however about 15% remain below the lower therapeutic threshold of MPA area under the curve (AUC) of 30 mg•hr•L early post transplant. A post hoc analysis of this study showed that a target MPA AUC >40 mg•hr•L was most effective. The primary objective of this study was to determine whether 4 g daily of MMF would result in a greater proportion achieving adequate MPA exposure. MATERIALS AND METHODS: MMF 4 g daily was used in tacrolimus treated de novo kidney transplant recipients. A 3-point limited sample strategy was used to measure MPA AUC on days 5 and 14. Doses were adjusted at day 5 if exposure was high. RESULTS: In 30 patients, the mean AUC was 63 ± 28 mg•hr•L on day 5, with 13% (4/30) ≤30 mg•hr•L and 57% (17/30) >60 mg•hr•L. The target MPA AUC was <40 mg•hr•L in 23% (7/30). Three patients developed gastrointestinal toxicity and required dose changes. Acute rejection occurred in only 2 patients (grade 1A and 2B) within 3 months (day 5 MPA AUCs were 29.9 and 33 mg•hr•L). On day 14 the mean AUC was 46 ± 17 mg•hr•L. Many were on MMF doses >2 g daily (8 on 3 g and 9 on 4 g daily). CONCLUSION: Compared to MMF 3 g daily, 4 g daily dose not result in a greater proportion adequately exposed. Rejections were few and occurred in the lower MPA exposed recipients. More than 50% of patients needed doses of MMF >2 g daily for 2 weeks to avoid underexposure. If intensified MPA dosing is considered, exceeding 3 g daily in tacrolimus-treated patients provides no added benefit. Copyright © 2012 by Lippincott Williams & Wilkins.

Bojko B.,University of Waterloo | Gorynski K.,University of Waterloo | Gomez-Rios G.A.,University of Waterloo | Knaak J.M.,Multi Organ Transplant Program | And 9 more authors.
Laboratory Investigation | Year: 2014

The techniques currently used for drug, metabolite, and biomarker determination are based on sample collection, and therefore they are not suitable for repeated analysis because of the high invasiveness. Here, we present a novel method of biochemical analysis directly in organ during operation without need of a separate sample collection step: solid-phase microextraction (SPME). The approach is based on flexible microprobe coated with biocompatible extraction phase that is inserted to the tissue with no damage or disturbance of the organ. The method was evaluated during lung and liver transplantations using normothermic ex vivo liver perfusion (NEVLP) and ex vivo lung perfusion (EVLP). The study demonstrated feasibility of the method to extract wide range of endogenous compounds and drugs. Statistical analysis allowed observing metabolic changes of lung during cold ischemic time, perfusion, and reperfusion. It was also demonstrated that the level of drugs and their metabolites can be monitored over time. Based on the methylprednisolone as a selected example, the impairment of enzymatic properties of liver was detected in the injured organs but not in healthy control. This finding was supported by changes in pathways of endogenous metabolites. The SPME probe was also used for analysis of perfusion fluid using stopcock connection. The evaluation of biochemical profile of perfusates demonstrated potential of the approach for monitoring organ function during ex vivo perfusion. The simplicity of the device makes it convenient to use by medical personnel. With the microprobe, different areas of the organ or various organs can be sampled simultaneously. The technology allows assessment of organ function by biochemical profiling, determination of potential biomarkers, and drug monitoring. The use of this method for preintervention analysis could enhance the decision-making process for the best possible personalized approach, whereas post-transplantation monitoring would be used for graft assessments and fast response in case of organ failure. © 2014 USCAP, Inc.

Boehnert M.U.,Multi Organ Transplant Program | Yeung J.C.,University of Toronto | Bazerbachi F.,Multi Organ Transplant Program | Knaak J.M.,Multi Organ Transplant Program | And 10 more authors.
American Journal of Transplantation | Year: 2013

We compared cold static with acellular normothermic ex vivo liver perfusion (NEVLP) as a novel preservation technique in a pig model of DCD liver injury. DCD livers (60 min warm ischemia) were cold stored for 4 h, or treated with 4 h cold storage plus 8 h NEVLP. First, the livers were reperfused with diluted blood as a model of transplantation. Liver injury was determined by ALT, oxygen extraction, histology, bile content analysis and hepatic artery (HA) angiography. Second, AST levels and bile production were assessed after DCD liver transplantation. Cold stored versus NEVLP grafts had higher ALT levels (350 ± 125 vs. 55 ± 35 U/L; p < 0.0001), decreased oxygen extraction (250 ± 65 mmHg vs. 410 ± 58 mmHg, p < 0.01) and increased hepatocyte necrosis (45% vs. 10%, p = 0.01). Levels of bilirubin, phospholipids and bile salts were fivefold decreased, while LDH was sixfold higher in cold stored versus NEVLP grafts. HA perfusion was decreased (twofold), and bile duct necrosis was increased (100% vs. 5%, p < 0.0001) in cold stored versus NEVLP livers. Following transplantation, mean serum AST level was higher in the cold stored versus NEVLP group (1809 ± 205 U/L vs. 524 ± 187 U/L, p < 0.05), with similar bile production (2.5 ± 1.2 cc/h vs. 2.8 ± 1.4 cc/h; p = 0.2). NEVLP improved HA perfusion and decreased markers of liver duct injury in DCD grafts. Normothermic ex vivo liver perfusion decreases hepatocyte death and bile duct injury of grafts obtained after cardiac death. © 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

Sener A.,Multi Organ Transplant Program | Khakhar A.K.,University of British Columbia | Nguan C.Y.,Apollo Hospitals | House A.A.,Multi Organ Transplant Program | And 3 more authors.
Journal of the Canadian Urological Association | Year: 2011

Introduction: Allosensitization is a significant obstacle to retransplantation for patients with primary renal graft failure. Methods: We assessed the impact of allograft nephrectomy (Group I) and weaning of immunosuppression (Group II) on percent panel reactive antibody (%PRA) at various time points after graft failure in 132 patients with a median follow-up of 47 months. Of these, 68% had allograft nephrectomy while 32% were placed on the waiting list and were either taken off immunosuppression, left on prednisone or on low-dose immunosuppressive therapy. Results: When groups were stratified into early (<6 months) and late (>6 months) graft failure, patients who had transplant nephrectomy for early failure demonstrated a decline in %PRA from 46% at time of graft failure to 27% at last follow-up (p = 0.02); conversely, %PRA continued to rise in Group II experiencing early allograft failure. Both Groups I and II patients with late graft failure maintained elevated %PRA at last follow-up. Conclusion: Allograft nephrectomy may play a role in limiting allosensitization in patients with early but not late graft failures. © 2011 Canadian Urological Association.

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