Rituximab reference vs biosimilar utilization for oncology vs nononcology indications.

OBJECTIVES: Limited data exist on the adoption of rituximab biosimilars vs the reference product by indication. Available data from real-world studies comparing rituximab biosimilar and reference use have focused predominantly on oncology indications. This is the first study to assess the utilization of the 3 US rituximab biosimilars vs the reference product. STUDY DESIGN: Comparative analysis. METHODS: Deidentified real-world data of rituximab, rituximab-abbs, rituximab-pvvr, and rituximab-arrx dispensations between December 31, 2018, and February 1, 2022, were extracted using Trisus Medication Compare (The Craneware Group). The primary outcome was rituximab reference vs biosimilar utilization for oncology vs nononcology indications. Results were stratified by on-label and off-label use and treatment settings. RESULTS: A total of 28,025 encounters were captured for rituximab and its biosimilars across 193 facilities (rituximab: n = 23,395; biosimilars, n = 4631 [rituximab-abbs: n = 2550; rituximab-pvvr, n = 2081; rituximab-arrx: n = 0]). Rituximab reference had higher dispensations for oncology (78.4%) and nononcology (88.3%) indications than its biosimilars (21.6% and 11.7%, respectively; P < .01). The 3-year annual trends from 2019 to 2021 revealed decreased rituximab reference utilization (99.99% to 40.1%) and increased biosimilar use (0.01% to 59.9%). Most oncology dispensations were on label (94.5%), whereas most nononcology dispensations were off label (73.6%; P < .01). A higher proportion of biosimilar use was attributed to on-label indications (67.7%; off-label, 32.2%) compared with rituximab reference (58.0% vs42.0%, respectively; P < .01). Nonacademic settings showed higher biosimilar adoption than academic settings (22.2% vs 10.3%, respectively; P < .01). CONCLUSIONS: Real-world evidence shows an increase in rituximab biosimilar adoption over time, with higher adoption for oncology vs nononcology indications and in nonacademic settings.

Fludrocortisone Plus Hydrocortisone Versus Hydrocortisone Alone as Adjunctive Therapy in Septic Shock: A Retrospective Cohort Study.

BACKGROUND: Trials evaluating hydrocortisone (HC) for septic shock are conflicting with all finding decreased time to shock reversal but few with mortality difference. Those with improved mortality included fludrocortisone (FC), but it is unknown if FC affected the outcome or is coincidental as there are no comparative data. OBJECTIVE: The objective of this study was to determine the effectiveness and safety of FC + HC versus HC alone as adjunctive therapy in septic shock. METHODS: A single-center, retrospective cohort study was conducted of medical intensive care unit (ICU) patients with septic shock refractory to fluids and vasopressors. Patients receiving FC + HC were compared with those receiving HC. Primary outcome was time to shock reversal. Secondary outcomes included in-hospital, 28-, and 90-day mortality; ICU and hospital length of stay (LOS); and safety. RESULTS: There were 251 patients included (FC + HC, n = 114 vs HC, n = 137). There was no difference in time to shock reversal (65.2 vs 71 hours; P = 0.24). Cox proportional hazards model showed time to first corticosteroid dose, full-dose HC duration, and use of FC + HC were associated with shorter shock duration, while time to vasopressor therapy was not. However, in 2 multivariable models controlling for covariates, use of FC + HC was not an independent predictor of shock reversal at greater than 72 hours and in-hospital mortality. No differences were seen in hospital LOS or mortality. Hyperglycemia occurred more frequently with FC + HC (62.3% vs 45.6%; P = 0.01). CONCLUSION AND RELEVANCE: FC + HC was not associated with shock reversal at greater than 72 hours or decreased in-hospital mortality. These data may be useful for determining corticosteroid regimen in patients with septic shock refractory to fluids and vasopressors. Future prospective, randomized studies are needed to further evaluate the role of FC in this patient population.

Risk of Coronavirus Disease 2019-Associated Pulmonary Aspergillosis Based on Corticosteroid Duration in Intensive Care Patients.

Background: Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) is a potential complication in critically ill COVID-19 patients. Corticosteroids are standard of care for hospitalized COVID-19 patients but carry an increased risk of secondary infections including CAPA. The objective of this study was to evaluate if duration of corticosteroid therapy ≤10 days versus >10 days affects the risk of developing CAPA. Methods: This was a retrospective cohort study of adult patients with severe COVID-19 pneumonia requiring mechanical ventilation who received at least 3 days of corticosteroid treatment. Incidence of CAPA and secondary outcomes were compared using appropriate bivariable analyses. Steroid duration was evaluated as an independent predictor in a logistic regression model. Results: A total of 278 patients were included (n = 169 for ≤10 days' steroid duration; n = 109 for >10 days). CAPA developed in 20 of 278 (7.2%) patients. Patients treated with >10 days of corticosteroid therapy had significantly higher incidence of CAPA (11.9% vs 4.1%; P = .0156), and steroid duration >10 days was independently associated with CAPA (odds ratio, 3.17 [95% confidence interval, 1.02-9.83]). Secondary outcomes including inpatient mortality (77.1% vs 43.2%; P < .0001), mechanical ventilation-free days at 28 days (0 vs 1.5; P < .0001), and secondary infections (44.9% vs 28.4% P = .0220) were worse in the >10 days cohort. Conclusions: Corticosteroid treatment >10 days in critically ill COVID-19 patients is associated with an increased risk of CAPA. Patients may require corticosteroids for reasons beyond COVID-19 and clinicians should be cognizant of risk of CAPA with prolonged courses.

Safety and efficacy of methylprednisolone versus dexamethasone in critically ill patients with COVID-19 acute respiratory distress syndrome: a retrospective study.

Background: Corticosteroids (CSs), specifically dexamethasone (DEX), are the treatment of choice for severe acute respiratory distress syndrome (ARDS) due to COVID-19 pneumonia (CARDS). However, data from both ARDS and relatively small CARDS clinical trials have suggested improved outcomes with methylprednisolone (MP) versus DEX. The objective of this retrospective cohort study was to compare the safety and effectiveness of MP and DEX in critically ill CARDS patients. Methods: The study cohort included CARDS patients admitted to a tertiary referral intensive care unit (ICU) between April and September 2020 who received at least 5 days of CSs for CARDS. Results: The cohort was notable for a high severity of illness (overall, 88.5% of patients required mechanical ventilation and 16% required vasopressors on admission). The DEX group (n = 62) was significantly older with a higher illness severity [Sequential Organ Failure Assessment (SOFA) 6 (4.75-8) versus 4.5 (3-7), p = 0.008], while the MP group (n = 51) received significantly more loading doses [19 (37.3%) versus 4 (6.5%), p < 0.0001]. MP was associated with a shorter time to intubation and more rapid progression to mortality [days to death: 18 (15-23) versus 27 (15-34), p = 0.026]. After correction for baseline imbalances in age and SOFA score, DEX was associated with improved mortality at 90 days compared with MP [hazard ratio (HR) = 0.43, 95% confidence interval (CI) = 0.23-0.80, p = 0.008]. However, there were no differences between rates of secondary infections during hospitalization or insulin requirements at 7 and 14 days. Conclusion: In this cohort of critically ill CARDS, choice of CS was associated with mortality but not adverse event profile, and thus warrants further investigation.

Hyperglycemia Post-Influenza Vaccine in Patients With Diabetes.

BACKGROUND: There are more than 350 reports of hyperglycemia post-influenza vaccine according to the Vaccine Adverse Effect Reporting System. Only one case report has been published detailing unusual post-vaccination hyperglycemia. The mechanism as to why hyperglycemia may occur post-vaccination has not been fully elucidated. OBJECTIVE: Primary: To identify hyperglycemia within the first 24 hours of influenza vaccine. Secondary: To identify transient property of hyperglycemia within 4 days after vaccine. METHODS: Multicenter prospective cohort study. Recruitment conducted throughout San Antonio, Texas, during 2018-2020 influenza seasons. Patients were included if 18 years or older, had diabetes mellitus, and currently checking their blood glucose daily. Patients excluded if they had a recent medication change that would effect their blood glucose readings. Patients had hemoglobin A1c and blood glucose measured prior to vaccination with a single dose (0.5 mL) of the tri-valent influenza vaccine intramuscularly. Glucose readings were collected within 24 hours post-vaccination and subsequent mornings for 4 days. RESULTS: A total of 34 patients were included. Average patient age was 75 years with 60% white, 30% black, and 10% Hispanic. Median fasting glucose pre-vaccination was significantly lower than the median value 0 to 24 hours post-vaccination (140 vs 203 mg/dL, P < 0.0001). CONCLUSION AND RELEVANCE: Hyperglycemia was noted 0 to 24 hours post-vaccination and was transient in nature with a return to baseline by post-vaccination day 2. This trial was conducted to close a potential gap in counseling regarding the flu vaccine and decrease any potential concern surrounding the vaccine in patients with diabetes that could lead to reduced vaccination rates.

Angiotensin II Use in Treatment of Refractory Shock Due to Benazepril and Amlodipine Toxic Ingestion.

INTRODUCTION: Calcium channel blockers (CCB) are a leading cause of ingestion-associated fatality. Angiotensin-converting enzyme inhibitor (ACEi) overdose as part of co-ingestion is common and associated with refractory shock. Treatment options to manage this profound vasoplegia are limited. We describe the first case of use of newly formulated Angiotensin II for treatment of severe ACEi and CCB poisoning. CASE REPORT: A 57-year-old man presented after suicide attempt by ingesting 20 tablets each of amlodipine 10 mg and benazepril 20 mg. His hypotension was initially managed with 35 mL/kg of crystalloid, norepinephrine, and hyperinsulinemic euglycemic therapy (HIET). His hemodynamics further deteriorated, and he developed lactic acidosis, electrolyte derangements, and renal dysfunction. Further complications of his ingestion included cardiac arrest, subsequent requirement for emergency cricothyrotomy, and renal replacement therapy. Maximal hemodynamic support with HIET therapy insulin drip 4.4 units/kg/hour, norepinephrine 2 mcg/kg/min, epinephrine 1 mcg/kg/min, vasopressin .06 units/hour, and intravenous lipid emulsion was unsuccessful. Ang II was started and titrated to maximal doses with dramatic improvement in hemodynamics. Within hours of starting Ang II, epinephrine was stopped and norepinephrine decreased by 50%. He was downgraded from the intensive care unit without any ongoing end-organ dysfunction. DISCUSSION: Isolated CCB overdoses have high complication rates and well-established treatments. Therefore, management of CCB and ACEi co-ingestion is typically driven by CCB poisoning algorithm. There are multiple reports of CCB and ACEi co-ingestions causing treatment-refractory shock. Therapeutic options are limited by toxicities and availability of salvage therapies. Ang II is a safe and highly effective option to manage these patients.

Prothrombin Complex Concentrate Use in Intracranial Hemorrhage Patients With Cirrhosis Not on Prior Anticoagulation.

BACKGROUND/OBJECTIVE: Patients with intracranial hemorrhage (ICH) have a 30-day mortality rate up to 52%, and the risk of mortality is increased in patients with disease-induced coagulopathy such as cirrhosis. The objective of this study was to evaluate whether 4F-PCC administration mitigates hematoma expansion in ICH patients with cirrhosis not currently receiving anticoagulation therapy compared to standard of care therapies. METHODS: This was a single-center, retrospective study comparing adult patients with ICH and history of cirrhosis who received 4F-PCC versus standard of care therapies. The primary outcome was rate of ICH expansion within 24 hours after admission. RESULTS: A total of 58 patients were included with 21 who received 4FPCC vs 37 who received standard of care therapies. The 4F-PCC group had a significantly higher number of patients with Child Pugh Class C cirrhosis (85.7% vs. 48.6%, P = 0.006), higher baseline INR (1.7 vs. 1.4, P = 0.001) and more patients with a spontaneous cause of hemorrhage (61.9% vs. 29.7%, P = 0.01). Stable follow-up head CT was achieved in 68.4% of patients who received 4F-PCC versus 72.7% of patients treated with standard of care therapies (P = 0.11). Patients who received 4F-PCC had a significantly greater change in INR within 24 hours (-0.2 vs. 0, P = 0.02) and higher rate of mortality (61.9% vs. 18.9%, P = 0.001). Baseline INR > 2 and surgical evacuation for ICH were associated with decreased odds of stable follow-up head CT in the multivariate logistic regression model. CONCLUSIONS: A single dose of 4F-PCC did not significantly improve the rate of stable head CT at 24 hours in patients with ICH and cirrhosis. Randomized clinical trials with larger patient populations are warranted to fully determine the role of 4F-PCC in this unique population.

Safety and Effectiveness of Sedation With Adjunctive Ketamine Versus Nonketamine Sedation in the Medical Intensive Care Unit.

BACKGROUND: Ketamine, an N-methyl-d-aspartate receptor antagonist with sedative and analgesic properties, is becoming more popular as an adjunctive sedative in the critically ill patients. METHODS: We conducted a single center, retrospective cohort study of patients admitted to the medical intensive care unit (MICU) between 2013 and 2018. Patients who received continuous infusion ketamine or nonketamine sedatives (NKS) including dexmedetomidine, fentanyl, midazolam, or propofol were identified. The primary outcome was percentage of Richmond Agitation-Sedation Scale (RASS) scores at goal in patients receiving ketamine as adjunct to NKS compared to those on NKS alone. RESULTS: A total of 172 patients were included (n = 86 ketamine, n = 86 NKS). Baseline characteristics were similar with the exception of antipsychotic use, which was higher in the ketamine group (P = .008). Percentage of RASS scores at goal was not different between groups (78.7% vs 81.4%, P = .29). Fewer patients in the ketamine group received continuous infusion fentanyl (76.7% vs 94.2%, P = .002). Patients on adjunctive ketamine required fewer days of intermittent benzodiazepines (0 [0-1] vs 1 [1-2], P < .0001). Patients receiving ketamine required less norepinephrine, receiving a median of 6.32 mg (2.4-20) versus 11.7 mg (5.2-45.2; P = .03). There was no difference in receipt of new antipsychotics or occurrence of arrhythmias. CONCLUSION: Addition of ketamine did not increase the percentage of RASS scores at goal versus NKS but was well tolerated. Ketamine was associated with reductions in norepinephrine requirements, days of intermittent benzodiazepine administration, and number of patients receiving continuous infusion fentanyl. Continuous infusion ketamine appears safe and effective for sedation in the MICU.

Effect of Therapeutic Interchange on Medication Changes Between Admission and Discharge.

Background: Therapeutic interchange (TI) is the dispensing of an alternative medication within the same class as the original medication. TI often occurs in hospitals; however, failure to return patients to their original medications may increase the risk of adverse effects following hospital discharge. Objective: The purpose of this study was to evaluate the relationship between TI and discharge medication changes, hospital readmission rates, and emergency department visit rates following hospital discharge. Methods: Patient demographic and medication data were collected retrospectively for patients admitted to a nonprofit, acute care hospital. The primary outcome was the relationship between TI and the rate of discharge medication changes. Secondary outcomes included types of discharge medication changes and the relationship between TI and both hospital readmissions and emergency department visits following hospital discharge. Results: A total of 497 patients accounting for 1072 medications were included; 21.2% of home medications were interchanged following admission, and 21.8% of home medications were changed at discharge. TI increased the incidence of discharge medication changes by 70% (odds ratio [OR] = 1.7, 95% confidence interval [CI] = 1.22-2.37, P = .0021). Cardiovascular agents were most likely to be changed at discharge (26%), and gastrointestinal agents were most likely to be interchanged (65%). Psychotropic agents were least likely to be changed at discharge (12%) or interchanged (7%). Neither TI nor discharge medication changes were predictive of 30-, 60-, or 90-day hospital readmission or emergency department visits following discharge. Conclusion and Relevance: This study was the first to examine the effects of TI on post-discharge outcomes. Despite being associated with an increased rate of discharge medication changes, the presence of TI did not correlate with hospital readmission or emergency department visit rates. This study supports the safety of TI.

Clonidine as a strategy for discontinuing dexmedetomidine sedation in critically ill patients: A narrative review.

PURPOSE: To review the efficacy and safety of transitioning from dexmedetomidine to clonidine to facilitate weaning of patients from sedation with dexmedetomidine. There is a paucity of data describing dexmedetomidine withdrawal syndrome (DWS) as well as clonidine's place in therapy for DWS. This review will describe and analyze current literature to provide clinical recommendations. SUMMARY: A MEDLINE literature search was performed to identify original research articles describing DWS and/or transitioning from dexmedetomidine to clonidine for the purpose of weaning patients from sedation with dexmedetomidine. Four case reports describing DWS, 3 case reports describing the use of clonidine to treat DWS, and 3 observational studies describing the use of clonidine to facilitate dexmedetomidine weaning were identified. The incidence of and risk factors for DWS are unknown; factors including patient age and dexmedetomidine infusion rate, loading dose, and discontinuation strategy have inconsistent associations with DWS. All cases of DWS have been associated with infusion durations greater than 72 hours. While there are limited data describing clonidine use for the treatment of dexmedetomidine withdrawal, clonidine appears to be beneficial for dexmedetomidine weaning and its use for that purpose has been well described. Clonidine dosages that have been assessed for discontinuing dexmedetomidine vary from 0.1 to 0.3 mg orally or enterally every 6 to 8 hours; one study assessed use of transdermal clonidine (100 µg/24 h patch). Patients with extensive cardiac comorbidities may be more susceptible to adverse effects of clonidine, which may limit the drug's use for DWS intervention. CONCLUSION: Despite limited supportive data, clonidine provides a promising option for sedation management in adult ICU patients, with successful transitions from dexmedetomidine reported within 24 hours after clonidine initiation.

Effect of Nonselective ß-Blockers on Mortality in Patients With End-Stage Cirrhosis.

Background: Data regarding safety of nonselective ß-blockers (NSBBs) in patients with end-stage cirrhosis are conflicting, making it difficult for practitioners to justify if benefits outweigh the risks. Objective: Evaluate the effect of NSBB use on mortality in patients with end-stage cirrhosis. Methods: We performed a dual-center retrospective study of patients who received octreotide for a variceal bleed. Patients were stratified into 2 groups based on whether or not a NSBB was prescribed at hospital discharge. The primary outcome was 24-month mortality. Multivariable logistic regression, with 24-month mortality as the dependent variable, was performed to identify independent risk factors for the primary outcome. Results: 255 patients met inclusion criteria; 24-month mortality was 32.8%. The NSBB and no-NSBB groups had similar mortality rates at 24 months (32.0% vs 38.5%, P = 0.51). Mortality at 3 months (11.6% vs 23.3%, P = 0.08) and 12 months (22.2% vs 30.0%, P = 0.36) were similar, and there were no differences in rate of variceal bleeding (22.7% vs 13.3%, P = 0.34) or cirrhosis-related cause of death (20.4% vs 23.3%, P = 0.81). In the multivariable model, age, model for end-stage liver disease with sodium and hepatocellular carcinoma were independent risk factors for 24-month mortality. NSBB therapy had no effect on 24-month mortality (adjusted odds ratio = 1.05; 95% CI = 0.32 to 3.40). Conclusion and Relevance: In patients with end-stage cirrhosis, use of NSBBs did not affect 24-month mortality. More research is needed to determine when, and if, NSBBs should be discontinued in end-stage cirrhosis.

Critically Ill Recipients of Weight-Based Fluconazole Meeting Drug-Induced Liver Injury Network Criteria.

Background: Fluconazole-associated liver injury is estimated to occur in <10% of patients; however, effect of weight-based fluconazole dosing on liver injury is unknown. Furthermore, no studies have systematically applied the Drug-Induced Liver Injury Network (DILIN) Criteria to identify patients who may have drug-induced liver injury in an intensive care unit (ICU) setting. Objective: This study evaluated how often patients met DILIN criteria when receiving fluconazole daily doses of <6 mg/kg versus ⩾6 mg/kg. Methods: This dual-center, retrospective cohort study was performed in hospitalized critically ill fluconazole recipients. We compared liver function tests (LFTs) upon fluconazole initiation to peak LFTs within 2 weeks after discontinuation using DILIN criteria. The primary objective was to evaluate the number of patients meeting DILIN criteria when receiving fluconazole daily doses of <6 mg/kg versus ⩾6 mg/kg. Secondary objectives were to evaluate incidence of patients meeting DILIN criteria in patients with renal dysfunction, cirrhosis, septic shock, or those receiving a loading dose. Results: Of 248 patients included, 90% had a documented fungal infection or received empiric therapy for suspected invasive candidiasis. In patients receiving <6 mg/kg of fluconazole, 55% (110/199) met DILIN criteria versus 46.9% (23/49) in the ⩾6 mg/kg cohort (P = .20). Only 14.5% of patients meeting DILIN criteria also met the definition for hepatocellular damage. Weight-based fluconazole dose and creatinine clearance <50 mL/min were not independent risk factors for meeting DILIN criteria. However, 77.3% of patients with cirrhosis met DILIN criteria (OR 4.84 [95% confidence interval, CI, 2.61-9.28]) and 76.3% with septic shock met DILIN criteria (OR 4.56 [95% CI, 2.44-8.88]). Conclusion: Weight-based fluconazole dosing did not affect the number of critically ill recipients who met DILIN criteria. However, DILIN criteria may overestimate the incidence of fluconazole-associated liver injury in critically ill patients.

Evaluation of prophylactic antibiotic regimens on recurrence and mortality in spontaneous bacterial peritonitis.

INTRODUCTION AND OBJECTIVES: Limited data describe current SBP epidemiology and specific secondary SBP prophylactic regimens, leading to variable prescribing practices. This work aims to compare 90-day and one-year SBP recurrence and mortality based on secondary SBP antibiotic prophylaxis regimens. MATERIALS AND METHODS: We performed a retrospective cohort of patients >18 years with an SBP diagnosis from 2010 to 2015 at two academic institutions. Eligible patients had ascitic PMN counts ≥250cells/mm3 or a positive ascitic culture. Patients were compared based on secondary SBP prophylaxis regimens (i.e., daily, intermittent, or no prophylaxis). RESULTS: Of 791 patients with ascitic fluid samples, 86 patients were included. Antibiotic prophylaxis included daily (n=34), intermittent (n=36), or no prophylaxis (n=16). Nearly half of SBP episodes had a positive ascitic fluid culture; 50% were gram-negative pathogens, and 50% were gram-positive pathogens. Daily and intermittent regimens had similar rates of recurrence at 90-days (19.4% vs. 14.7%, p=0.60) and one-year (33.3% vs. 26.5%, p=0.53). Similarly, mortality did not differ among daily and intermittent regimens at 90-days (32.4% vs. 30.6%, p=0.87) or one-year (67.6% vs. 63.9%, p=0.74). When comparing any prophylaxis vs. no prophylaxis, there were no differences in 90-day or one-year recurrence or mortality. CONCLUSIONS: In patients with a history of SBP, our data indicate similar outcomes with daily, intermittent, or no secondary antibiotic prophylaxis. With available data, including ours, demonstrating a changing epidemiology for SBP pathogens, further data is required to determine if traditional approaches to secondary SBP prophylaxis remain appropriate.

Prophylactic Acid-Suppressive Therapy in Hospitalized Adults: Indications, Benefits, and Infectious Complications.

Acid-suppressive therapy for prophylaxis of stress ulcer bleeding is commonly prescribed for hospitalized patients. Although its use in select, at-risk patients may reduce clinically significant gastrointestinal bleeding, the alteration in gastric pH and composition may place these patients at a higher risk of infection. Although any pharmacologic alteration of the gastric pH and composition is associated with an increased risk of infection, the risk appears to be highest with proton pump inhibitors, perhaps owing to the potency of this class of drugs in increasing the gastric pH. With the increased risk of infection, universal provision of pharmacologic acid suppression to all hospitalized patients, even all critically ill patients, is inappropriate and should be confined to patients meeting specific criteria. Nurses providing care in critical care areas may be instrumental in screening for appropriate use of acid-suppressive therapy and ensuring the drugs are discontinued upon transfer out of intensive care or when risk factors are no longer present.

Effect of Body Weight on Hemodynamic Response in Patients Receiving Fixed-Dose Vasopressin for Septic Shock.

BACKGROUND: Fixed-dose vasopressin is an adjunctive therapy to norepinephrine (NE) to raise mean arterial pressure (MAP) and decrease NE requirements in patients with septic shock. It is unknown if weight affects hemodynamic response to vasopressin or if a weight-based vasopressin strategy is superior to fixed dosing. OBJECTIVE: The primary objective was to evaluate effect of body weight on response to vasopressin as measured by change in MAP 1 hour post-vasopressin initiation. METHODS: A single-center, retrospective study was performed in patients with septic shock. Baseline characteristics, catecholamine and vasopressin requirement, response to therapy, and adverse events were collected. RESULTS: Forty patients were included who received a fixed-dose vasopressin in addition to catecholamine infusions. No correlation was found in the primary outcome of change in MAP at 1 hour after vasopressin initiation compared with vasopressin dose relative to patient weight or body mass index (BMI). Change in MAP at 6 and 12 hours was not significant. In the obese population (n = 9), there was a significant negative correlation between BMI and change in MAP at 6 hours (correlation coefficient r = -0.951; P = 0.0009). Linear regression analysis confirmed that vasopressin dose relative toweight was independently associated with change in MAP at 1, 6, and 12 hours, whereas changes in NE dosing were not. CONCLUSION: Increasing weight-based dosing of vasopressin did not correlate with change in MAP when used with catecholamine vasopressors in septic shock. However, fixed-dose vasopressin may not be sufficient in obese septic shock patients with a BMI ≥30 kg/m(2).

Building Cultural Sensitivity and Interprofessional Collaboration Through a Study Abroad Experience.

BACKGROUND: Study abroad (SA) experiences for health professions students may be used to heighten cultural sensitivity to future patients and incorporate interprofessional education (IPE). METHOD: Two groups of nursing and pharmacy students participated in an SA elective over a 2-year period, traveling to China and India. RESULTS: Both groups improved significantly in knowledge, awareness, and skills following the travel experiences. Student reflections indicate that the SA experience was transformative, changing their views of travel, other cultures, personal environment, collaboration with other health professionals, and themselves. CONCLUSION: Use of SA programs is a novel method to encourage IPE, with a focus on enhancing the acquisition of cultural competency skills.

Evaluation of Clinical and Communication Skills of Pharmacy Students and Pharmacists with an Objective Structured Clinical Examination.

Objective. To evaluate how effectively pharmacy students and practicing pharmacists communicate and apply knowledge to simulations of commonly encountered patient scenarios using an objective structured clinical examination (OSCE). Design. Second-, third-, and fourth-year pharmacy students completed an OSCE as part of their required courses in 2012 and 2013. All students in both years completed identical OSCE cases. Licensed pharmacists were recruited to complete the OSCE and serve as controls in 2012. A survey assessed student perception and acceptance of the OSCE as well as student confidence in performance. Assessment. Licensed pharmacists had significantly higher clinical and communication skills scores than did pharmacy students. Student progression in communication and clinical skills improved significantly over time. Survey results indicated that students felt the OSCE was well-structured and assessed clinical skills taught in pharmacy school; 86% of students felt confident they could provide these skills. Conclusion. Objective structured clinical examinations can evaluate clinical competence and communication skills among professional students. Implementation of OSCEs may be an effective tool for assessment of the Center for the Advancement of Pharmacy Education domains.

Vasopressin Associated With an Increase in Return of Spontaneous Circulation in Acidotic Cardiopulmonary Arrest Patients.

BACKGROUND: During respiratory and metabolic acidosis, the vasoconstrictive effects of epinephrine may be blunted, whereas the response to vasopressin remains unchanged. The impact of this effect during advanced cardiac life support (ACLS) remains unclear. OBJECTIVE: Determine if vasopressin therapy in combination with epinephrine was associated with improved outcomes in patients with cardiac arrest compared to epinephrine alone. The primary outcome was difference in rate of return of spontaneous circulation (ROSC). Secondary outcomes included evaluation of rates of ROSC for patients with an initial pH <7.2 and by initial pulseless rhythm. METHODS: Single-center, retrospective review conducted from July 2010 to July 2012. Patients ≥18 years of age with documented cardiac arrest requiring ACLS and vasopressor therapy were included. RESULTS: A total of 101 patients met inclusion criteria. There was no difference in rate of ROSC (56% vs 60%, P = 0.68) or survival to hospital discharge (9% vs 5%, P = 0.46) between patients who received vasopressin in combination with epinephrine (n = 43) compared to epinephrine alone (n = 58). Subgroup analysis of ROSC in patients with an arterial pH of <7.2 (n = 35) showed an increased rate of ROSC (63% vs 37%, P = 0.01) in the vasopressin plus epinephrine group versus the epinephrine alone group, respectively. Subgroup analysis by initial cardiac rhythm showed no difference in rate of ROSC. CONCLUSIONS: Vasopressin in combination with epinephrine demonstrated improved ROSC in cardiac arrest patients with initial arterial pH <7.2 compared with epinephrine alone, without improving survival to hospital discharge.

Use of propofol-containing versus benzodiazepine regimens for alcohol withdrawal requiring mechanical ventilation.

BACKGROUND: When chronic, excessive alcohol intake is abruptly halted, patients are at risk for developing life-threatening alcohol withdrawal syndrome (AWS). Benzodiazepines have established efficacy, yet some patients' symptoms persist despite treatment with high doses. OBJECTIVES: The study objective was to compare time to resolution of AWS symptoms in mechanically ventilated patients receiving propofol-containing versus benzodiazepine infusions. METHODS: This study was a retrospective cohort analysis of adult patients with ICD-9 codes for AWS who required mechanical ventilation for AWS symptoms. RESULTS: A total of 1637 records were reviewed, and 64 were included. Propofol-containing regimens were used in 46 cases (72%), whereas benzodiazepine infusion monotherapy accounted for 18 cases (28%). Patients were predominantly male (97%), with a mean age of 45 years. Lorazepam-equivalent benzodiazepine doses given prior to intubation were greater in patients receiving propofol infusion (56 vs 15 mg, P = .03). Time to resolution of AWS symptoms for propofol- and benzodiazepine-treated patients was 8 and 7 days, respectively (P = .34). Median hospital and intensive care unit lengths of stay were similar (9 vs 10 days and 4 vs 4 days, respectively; P > .05 for both comparisons), as were days of mechanical ventilation (4 vs 3 days, P = .98). Patients in the benzodiazepine infusion monotherapy group required numerically increased amounts of benzodiazepine bolus doses while on continuous sedation, compared with patients receiving propofol infusion (36 vs 10 mg, P = .06). CONCLUSIONS: Propofol and Benzodiazepine-treated patients with AWS requiring mechanical ventilation experienced similar days of AWS symptoms, length of stay, and mechanical ventilation.

Fenofibrate-associated nephrotoxicity: a review of current evidence.

PURPOSE: The literature describing fenofibrate-associated nephrotoxicity was reviewed. SUMMARY: Fenofibrate-associated nephrotoxicity is an underrecognized adverse effect that is being reported with increasing frequency in the medical literature. A MEDLINE search identified articles describing fenofibrate-associated nephrotoxicity. Two retrospective chart reviews reported this adverse reaction in transplant recipients and patients with renal insufficiency. A case series of six patients noted that the adverse reaction also occurred in patients without a predisposition to renal injury. Two small prospective studies have examined fenofibrate-associated nephrotoxicity, with conflicting findings regarding the mechanism. Finally, a large retrospective review and a population-based cohort study found that patients with preexisting renal disease or taking high-dosage fenofibrate have a higher risk of developing fenofibrate-associated nephrotoxicity. Fenofibrate-associated nephrotoxicity was shown to be reversible with both discontinuation and continued use of fenofibrate, though one study found that the elevations in serum creatinine (SCr) levels were permanent in study participants. Some argue that SCr elevations described in these articles were not due to renal toxicity but may be attributed to reversible mechanisms. While several mechanisms may be biologically plausible, none of the theories have been tested in clinical trials. A possible mechanism for the increase in SCr levels may include changes in renal hemodynamics causing volume depletion and the impairment of generation of vasodilatory prostaglandins, leading to renal vasoconstriction. CONCLUSION: Fenofibrate-associated nephrotoxicity is an underrecognized adverse drug reaction. Several published reports have detailed possible etiologies; however, data detailing the true incidence of fenofibrate-associated nephrotoxicity and its associated risk factors are limited.