Conducting Multicenter Residency Research.

PURPOSE: Conducting well designed pharmacy resident research projects has inherent challenges including inadequate sample size, a lack of time, decreased generalizability, and inadequate research support. A way to overcome these barriers is through conducting multicenter research projects. However, this approach may also bring new challenges. Therefore, the purpose of this article is to provide a general approach for pharmacy preceptors and leaders on implementation of multicenter residency research. SUMMARY: This article includes a general approach to conducting multicenter research from experienced individuals based upon their successes and failures. A timeline-based format is presented to lay the groundwork for implementation of this approach. Key topics in this paper include establishing a research overview committee, research question development, Institutional Review Board considerations, site recruitment, authorship discussions, resident coordination, protocol development, data collection, manuscript development, and considerations after residency. The approach maintains a critical focus on the individual residents ability to achieve American Society of Health-System Pharmacists accreditation standards for conducting research while operating in a collaborative manner. CONCLUSION: Conducting multicenter residency research projects requires a team-based approach and advanced planning. This approach has the potential to improve pharmacy resident project quality.

Antimicrobial resistance profiles of Escherichia coli and prevalence of extended-spectrum beta-lactamase-producing Enterobacteriaceae in calves from organic and conventional dairy farms in Switzerland.

This study compared the antimicrobial resistance (AMR) among commensal Escherichia coli in the fecal microbiota of young calves raised on organic and on conventional dairy farms in Switzerland. Further, fecal carriage of extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae was assessed for calves from both farming systems. Where possible, data on antimicrobial usage (AMU) were obtained. Antimicrobial susceptibility testing was performed on a total of 71 isolates using the disk diffusion method. ESBL producers were characterized by polymerase chain reaction-based multilocus sequence typing and sequencing of the blaESBL genes. Organically raised calves were significantly more likely to harbor E. coli that showed AMR to ampicillin (odds ratio [OR]: 2.78, 95% confidence interval [CI]: 1.02-7.61, p = 0.046), streptomycin (OR: 3.22, 95% CI: 1.17-8.92, p = 0.046), kanamycin (OR: 11.3, 95% CI: 2.94-43.50, p < 0.001), and tetracycline (OR: 3.25, 95% CI: 1.13-9.31, p = 0.028). Calves with reported AMU were significantly more likely to harbor E. coli with resistance to ampicillin (OR: 3.91, 95% CI: 1.03-14.85, p = 0.045), streptomycin (OR: 4.35, 95% CI: 1.13-16.7, p = 0.045), and kanamycin (OR: 8.69, 95% CI: 2.01-37.7, p = 0.004). ESBL-producing Enterobacteriaceae (18 E. coli and 3 Citrobacter braakii) were detected exclusively among samples from conventionally farmed calves (OR: infinity [∞], 95% CI: 2.3-∞, p < 0.0013). The observations from this study suggest that AMR is highly prevalent among commensal E. coli in young dairy calves, irrespective of the farm management system, with proportions of certain resistance phenotypes higher among organic calves. By contrast, the occurrence of ESBL producers among young dairy calves may be linked to factors associated with conventional farming.

Deviant Dosing: A Post hoc Analysis of Pharmacist Characteristics Related to Renal Dosing Decisions.

BACKGROUND: A recent study demonstrated that pharmacists presented with multiple estimating equations deviated from recommended dosing guidance more often than pharmacists who were presented with a single estimate on clinical vignettes. OBJECTIVES: To identify characteristics associated with an increased tendency to deviate from approved recommendations. METHODS: Participant data were split into 2 cohorts: pharmacists who chose a dose that was inconsistent with dosing recommendations on at least 1 of the 4 vignettes and pharmacists who did not deviate on a single case. Bivariate analysis of demographic- and practice-related variables were conducted between groups using the χ2, Mann-Whitney U, or Student t-test for nominal, ordinal, and continuous variables, respectively. Statistically different covariates between groups (P < 0.05) were assessed using multivariable linear regression. RESULTS: Survey data from 154 inpatient pharmacists, 71 of whom deviated on at least 1 clinical vignette, were analyzed. On univariate analysis, deviator pharmacists were more likely to have completed postgraduate residency training (68% vs 41%; P < 0.05) and board certification (39% vs 20%; P < 0.05). Deviator pharmacists were also more likely to have been presented with multiple renal estimates as opposed to a single estimate and had differing renal dosing practices at baseline (P < 0.05). Following multivariable regression, residency training, mismatched baseline renal practices, and multiple renal estimates remained independent predictors (P < 0.05) of dosing deviation. CONCLUSION AND RELEVANCE: Higher clinical training, practice variation, and multiple renal estimates may affect renal dosing practices. Prospective, statistically powered studies are needed to verify these hypotheses.

The Impact of Multiple Renal Estimates on Pharmacist Dosing Recommendations: A Randomized Trial.

BACKGROUND: Numerous equations are used for estimation of renal function, and many electronic medical records report multiple clearance estimates to assist with drug dosing. It is unknown whether the presence of multiple clearance estimates affects clinical decision-making. OBJECTIVE: To determine whether the presence of multiple renal clearance estimates affects pharmacist drug dosing decisions. METHODS: A randomized trial in the form of an electronic survey including 4 clinical vignettes was delivered to hospital pharmacists. Vignettes consisted of a patient presenting with an acute pulmonary embolism requiring enoxaparin therapy. Pharmacists were randomized to receive a single estimate of renal function or multiple estimates for all vignettes. The primary outcome was deviation from approved recommendations on at least 1 vignette. The χ2 test was used to detect differences in deviation rates between groups. Logistic regression was performed to adjust for the effects of potentially confounding variables. RESULTS: A total of 154 studies were completed (73 in the multiple-estimate group and 81 in the single-estimate group). Pharmacists presented with multiple renal estimates were significantly more likely to deviate from recommended dosing regimens than pharmacists presented with a single estimate (54.7% vs 38.2%; P = 0.04). The results were driven primarily by the 2 vignettes that included discordance among Cockcroft-Gault equation creatinine clearance estimates. Logistic regression identified multiple estimates as the only independent predictor of deviation (P = 0.04). CONCLUSION AND RELEVANCE: Pharmacists provided with a single renal clearance estimate were more likely to adhere to approved dosing recommendations than pharmacists provided with multiple estimates.

Outcomes associated with apixaban vs warfarin in patients with renal dysfunction.

Apixaban in patients with impaired renal function is supported by limited data. Landmark clinical trials evaluating apixaban in patients with atrial fibrillation and/or acute venous thromboembolism excluded patients with creatinine clearance (CrCl) <25 mL/min. This multicenter, retrospective chart review was conducted to evaluate the safety and effectiveness of apixaban compared with warfarin in patients with CrCl <25 mL/min. Included patients were newly initiated on apixaban or warfarin for at least 45 days with a CrCl <25 mL/min. Patients were evaluated for thrombosis and bleeding outcomes 6 months following initiation of anticoagulation. The primary outcome was the time to first bleeding or thrombosis event. A total of 128 patients met inclusion criteria in the apixaban group and 733 patients in the warfarin group. Time to first bleeding or thrombosis event was significantly different between the apixaban and warfarin groups. Cox proportional hazards model was conducted to control for potential confounding factors for the primary outcome. After controlling for atrial fibrillation and coronary artery bypass grafting, risk of thrombotic and bleeding events was lower in the apixaban group (hazard ratio, 0.47; 95% confidence interval, 0.25-0.92). There was not a statistical difference between time to thrombosis (83 days vs 54 days, P = .648), rate of thrombosis (5.5% vs 10.3%, P = .08), time to bleeding (46 days vs 54 days, P = .886), or rate of bleeding (5.5% vs 10.9%, P = .06). The severity of bleeding and thrombotic events was not different between groups. Apixaban may serve as a reasonable alternative compared with warfarin in patients with severe renal dysfunction.

Therapeutic Enoxaparin in the Morbidly Obese Patient: A Case Report and Review of the Literature.

Enoxaparin is a low molecular weight heparin commonly used in the treatment of venous thromboembolisms (VTEs); however, evidence on optimal empiric dosing recommendations are lacking in patients with morbid obesity. Utilization of an absolute dose cap, anti-Xa monitoring, and reduced empiric dosing are among the techniques used in this population. We describe a case of a morbidly obese man (body-mass index, BMI: 68.2 kg/m2, total body weight: 236 kg) who required therapeutic enoxaparin for suspected pulmonary embolism (PE) and critical limb ischemia as a bridge therapy during warfarin initiation. An initial empiric dose of 200 mg Q12 hours (0.85 mg/kg) resulted in an anti-Xa level of 1.01 IU/mL following the fifth dose, and no dose modification was deemed necessary. He experienced no adverse effects from treatment. This report adds to a growing body of evidence illustrating the need for reduced empiric weight-based doses of enoxaparin in the morbidly obese population and raises the question of whether dose capping is an appropriate practice in the clinical setting of morbidly obese patients with acute VTE.

Relationship Status between Vancomycin Loading Dose and Treatment Failure in Patients with MRSA Bacteremia: It's Complicated.

INTRODUCTION: A one-time vancomycin loading dose of 25-30 mg/kg is recommended in the current iteration of the vancomycin consensus guidelines in order to more rapidly achieve target serum concentrations and hasten clinical improvement. However, there are few clinical data to support this practice, and the extents of its benefits are largely unknown. METHODS: A multicenter, retrospective, cohort study was performed to assess the impact of a vancomycin loading dose (≥ 20 mg/kg) on clinical outcomes and rates of nephrotoxicity in patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. The study matched patients in a 1:1 fashion based on age, Pitt bacteremia score, and bacteremia source. The primary outcome was composite treatment failure (30-day mortality, bacteremia duration ≥ 7 days after vancomycin initiation, persistent signs and symptoms of infection ≥ 7 days after vancomycin initiation, or switch to an alternative antimicrobial agent). Secondary outcomes included duration of bacteremia, length of stay post-bacteremia onset, and nephrotoxicity. RESULTS: A total of 316 patients with MRSA bacteremia were included. Median first doses in the loading dose and non-loading dose groups were 23.0 mg/kg and 14.3 mg/kg, respectively (P < 0.001). No difference was found in composite failure rates between the non-loading dose and loading dose groups (40.5% vs. 36.7%; P = 0.488) or in the incidence of nephrotoxicity (12.7% vs. 16.5%; P = 0.347). While multivariable regression modeling showed receipt of a vancomycin loading dose on a mg/kg basis was not significantly associated with composite failure [aOR 0.612, 95% CI (0.368-1.019)]; post hoc analyses demonstrated that initial doses ≥ 1750 mg were independently protective against failure [aOR 0.506, 95% CI (0.284-0.902)] without increasing the risk for nephrotoxicity [aOR 0.909, 95% CI (0.432-1.911)]. CONCLUSION: These findings suggest that initial vancomycin doses above a certain threshold may decrease clinical failures without increasing toxicity and that weight-based dosing might not be the optimal strategy.

Nicardipine Associated Risk of Short-Term Mortality in Critically Ill Patients with Ischemic Stroke.

BACKGROUND: Hypertensive emergency is commonly associated with acute ischemic stroke and can be a predictor of poor outcome in these patients. Nicardipine and labetalol are commonly administered for the treatment of acute hypertension following stroke. Yet, data are lacking on the safety of these agents in this setting. OBJECTIVE: This study aimed to determine all-cause in-hospital mortality, medication-related hypotensive episodes, development of hospital acquired infections and hospital length of stay between nicardipine and labetalol use for the management of hypertension after acute ischemic stroke. METHODS: This retrospective study used a prospective database of individuals admitted to the neurointensive care unit at a university-based hospital over 39 months. Patients with confirmed ischemic strokes were included in this analysis. Data were recorded for administration of nicardipine and labetalol following acute stroke. RESULTS: A total of 244 patients with acute ischemic stroke were included in this analysis (mean age, 64.3 ± 15 years; 52.2% males). Nicardipine use after acute ischemic stroke was associated with an increased risk of 30-day mortality (odds ratio [OR]: 4.6, 95% confidence interval [CI] 1.3-15.7; P = .02). A single episode of hypotension in the first 72hours of admission was also significantly associated with mortality (OR 4.35 [95% CI 1.2-14.9]; P = .02). CONCLUSIONS: Nicardipine was associated with an increased risk of short-term mortality after acute ischemic stroke. This may have been due to hypotension, tachycardia, or pulmonary edema which were not apparent in our study. Further studies are required to elucidate the cause of this association.

Apixaban for the treatment of cerebral venous thrombosis: A case series.

BACKGROUND: Venous thrombosis affecting cerebral veins and sinuses (CVT) is an uncommon neurological condition. Traditionally patients are treated with intravenous heparin followed by an oral vitamin K antagonist like warfarin. Direct oral anticoagulants (DOACs) may offer advantages over warfarin. There is evidence to demonstrate the effectiveness of both dabigatran and rivaroxaban. No data, however, has been published describing the use of apixaban in patients with CVT. METHODS: Report of three cases of CVT and review literature on available treatment options; efficacy and safety of novel oral anticoagulants in patients with systemic thrombosis. RESULTS: All patients presented with typical features of CVT. After confirming the diagnosis, they were acutely treated with heparin and later discharged on apixaban. During follow up visits, they tolerated apixaban well and did not have any bleeding complications. Follow up scans showed resolution of the thrombus and recanalization. CONCLUSION: CVT is an uncommon neurological condition and is often complicated by associated intraparenchymal hemorrhage. Although not recommended in current guidelines, apixaban may be a safe and effective option for the treatment of CVT.

Anticoagulation Bridge Therapy in Patients with Atrial Fibrillation: Recent Updates Providing a Rebalance of Risk and Benefit.

In 2011 we reviewed clinical updates and controversies surrounding anticoagulation bridge therapy in patients with atrial fibrillation (AF). Since then, options for oral anticoagulation have expanded with the addition of four direct oral anticoagulant (DOAC) agents available in the United States. Nonetheless, vitamin K antagonist (VKA) therapy continues to be the treatment of choice for patients who are poor candidates for a DOAC and for whom bridge therapy remains a therapeutic dilemma. This literature review identifies evidence and guideline and consensus statements from the last 5 years to provide updated recommendations and insight into bridge therapy for patients using a VKA for AF. Since our last review, at least four major international guidelines have been updated plus a new consensus document addressing bridge therapy was released. Prospective trials and one randomized controlled trial have provided guidance for perioperative bridge therapy. The clinical trial data showed that bridging with heparin is associated with a significant bleeding risk compared with not bridging; furthermore, data suggested that actual perioperative thromboembolic risk may be lower than previously estimated. Notably, patients at high risk for stroke have not been adequately represented. These findings highlight the importance of assessing thrombosis and bleeding risk before making bridging decisions. Thrombosis and bleeding risk tools have emerged to facilitate this assessment and have been incorporated into guideline recommendations. Results from ongoing trials are expected to provide more guidance on safe and effective perioperative management approaches for patients at high risk for stroke.