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PURPOSE: Patients treated with therapeutic hypothermia (TH) and continuous insulin may be at increased risk of hyperglycemia or hypoglycemia, particularly during temperature transitions. This study aimed to evaluate frequency of glucose excursions during each phase of TH and to characterize glycemic control patterns in relation to survival. METHODS: Patients admitted to a tertiary care hospital for circulatory arrest and treated with both therapeutic hypothermia and protocol-based continuous insulin between January 2010 and June 2013 were included. Glucose measures, insulin, and temperatures were collected through 24 hours after rewarming. RESULTS: 24 of 26 patients experienced glycemic excursions. Hyperglycemic excursions were more frequent during initiation versus remaining phases (36.3%, 4.3%, 2.5%, and 4.0%, p = 0.002). Hypoglycemia occurred most often during rewarming (0%, 7.7%, 23.1%, and 3.8%, p = 0.02). Patients who experienced hypoglycemia had higher insulin doses prior to rewarming (16.2 versus 2.1 units/hr, p = 0.03). Glucose variation was highest during hypothermia and trended higher in nonsurvivors compared to survivors (13.38 versus 9.16, p = 0.09). Frequency of excursions was also higher in nonsurvivors (32.3% versus 19.8%, p = 0.045). CONCLUSIONS: Glycemic excursions are common and occur more often in nonsurvivors. Excursions differ by phase but risk of hypoglycemia is increased during rewarming.

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OBJECTIVES: To determine whether discontinuation of chronic antidepressant therapy is associated with a higher risk of antidepressant discontinuation syndrome (ADS) symptoms in patients admitted to the intensive care unit (ICU) when compared with those who were continued on therapy and to identify factors associated with increased risk of ADS in this population. DESIGN: Single-center retrospective observational cohort study. SETTING: ICUs in a tertiary care hospital. PATIENTS: A total of 106 adult patients, admitted to the ICU between September 2013 and August 2014, who had a length of stay of 72 hours or longer and who were receiving chronic selective serotonin inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) before admission. MEASUREMENTS AND MAIN RESULTS: Patients were classified as continued or discontinued from therapy based on initiation of home SSRI/SNRI therapy within 48 hours of admission. The primary end point was incidence of ADS symptoms. Type of symptoms, receipt of symptom-related therapies, and length of stay were also assessed. Sequential logistic regression analysis was used to determine the impact of discontinuation while controlling for other risk factors. Therapy was discontinued in 38.7% of patients. The risk of developing ADS symptoms was higher in discontinued patients (unadjusted odds ratio [OR] 2.6, 95% confidence interval [CI] 1.12-6.07, p=0.024). After adjusting for covariates, the odds of ADS increased (adjusted OR 3.8, 95% CI 1.3-11.7, p=0.018). Female sex was associated with an increase in risk of ADS (OR 3.4, 95% CI 1.2-10.0, p=0.026). Affective symptoms were the most prevalent type reported (34.1% vs 10.8%, p=0.005). Use of symptom-related therapies and length of stay did not differ between groups. CONCLUSION: Abrupt discontinuation of SSRI/SNRI therapy increases the risk of ADS symptoms in critically ill patients, particularly in females. These results underscore the importance of continuation of home antidepressant therapy even in the setting of critical illness.

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BACKGROUND: Scant literature exists evaluating utilization patterns for direct oral anticoagulants (DOACs). OBJECTIVES: The primary objective was to assess DOAC prescribing in patients with venous thromboembolism (VTE) and nonvalvular atrial fibrillation (NVAF) in outpatient clinics. Secondary objectives were to compare utilization between family medicine (FM) and internal medicine (IM) clinics, characterize potentially inappropriate use, and identify factors associated with adverse events (AEs). METHODS: This was a retrospective cohort study of adults with NVAF or VTE who received a DOAC at FM or IM clinics between 10/19/2010 and 10/23/2014. Descriptive statistics were utilized for the primary aim. Fisher's exact test was used to evaluate differences in prescribing using an adapted medication appropriateness index. Logistic regression evaluated factors associated with inappropriate use and AEs. RESULTS: One-hundred twenty patients were evaluated. At least 1 inappropriate criterion was met in 72 patients (60.0%). The most frequent inappropriate criteria were dosage (33.0%), duration of therapy (18.4%), and correct administration (18.0%). Apixaban was dosed inappropriately most frequently. There was no difference in dosing appropriateness between FM and IM clinics. The odds of inappropriate choice were lower with apixaban compared to other DOACs (odds ratio [OR]=0.088; 95% confidence interval [CI] 0.008-0.964; p=0.047). Twenty-seven patients (22.5%) experienced an AE while on a DOAC, and the odds of bleeding doubled with each inappropriate criterion met (OR=1.949; 95% CI 1.190-3.190; p=0.008). CONCLUSION: Potentially inappropriate prescribing of DOACs is frequent with the most common errors being dosing, administration, and duration of therapy. These results underscore the importance of prescriber education regarding the appropriate use and management of DOACs.

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Sepsis in older adults has many challenges that affect rate of septic diagnosis, treatment, and monitoring parameters. Numerous age-related changes and comorbidities contribute to increased risk of infections in older adults, but also atypical symptomatology that delays diagnosis. Due to various pharmacokinetic/pharmacodynamic changes in the older adult, medications are absorbed, metabolized, and eliminated at different rates as compared to younger adults, which increases risk of adverse drug reactions due to use of drug therapy needed for sepsis management. This review provides information to aid in diagnosis and offers recommendations for monitoring and treating sepsis in the older adult population.

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BACKGROUND: Previous studies were conducted in all hospitalized patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia to determine safety and effectiveness of guideline-recommended, weight-based dosing of vancomycin. In these studies, it was observed that severely ill patients (Pitt bacteremia score ≥4 or intensive care unit [ICU] patients) were at an increased risk of mortality and/or nephrotoxicity. Therefore, a subanalysis of the effect of guideline-recommended vancomycin dosing on in-hospital mortality and nephrotoxicity in ICU patients with MRSA bacteremia was conducted. METHODS: This multicenter, retrospective, cohort study was conducted in a subset of ICU patients from a previous MRSA bacteremia study. Patients were ≥18 years old and received ≥48 hours of empiric vancomycin from July 1, 2002, to June 30, 2008. The incidence of nephrotoxicity and in-hospital mortality was compared in patients who received guideline-recommended dosing (at least 15 mg/kg per dose) to patients who received non-guideline-recommended dosing of vancomycin. Multivariable generalized linear mixed-effects models were constructed to determine independent risk factors for in-hospital mortality and nephrotoxicity. RESULTS: Guideline-recommended dosing was received by 34% of patients (n = 137). Nephrotoxicity occurred in 35% of patients receiving guideline-recommended dosing and 39% receiving non-guideline-recommended dosing (P = 0.67). In-hospital mortality rate was 24% among patients who received guideline-recommended dosing compared with 31% for non-guideline-recommended dosing (P = 0.40). Guideline-recommended dosing was not associated with nephrotoxicity (odds ratio: 1.10; 95% confidence interval: 0.43-2.79) or in-hospital mortality (odds ratio: 0.54; 95% confidence interval: 0.22-1.36) in the multivariable analysis. CONCLUSIONS: Guideline-recommended dosing of vancomycin in ICU patients with MRSA bacteremia is not significantly associated with nephrotoxicity or in-hospital mortality. However, the 7% absolute difference for in-hospital mortality suggests that larger studies are needed.

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BACKGROUND: Penicillin (PCN) accounts for most cases of antibiotic allergies. Reported PCN allergy deprives the patient from this class of antibiotics and creates hesitancy in using other beta-lactam antibiotics. The aim of this study is to report the prevalence of self-reported PCN allergy among adult patients admitted to the hospital and to examine the probable validity of these reports. METHODS: A questionnaire was conducted among 192 patients with self-reported PCN allergy who were admitted to a community hospital between July 25, 2011 and January 25, 2012. Patients admitted with an infection and treated with a beta-lactam were also followed until hospital discharge. RESULTS: The mean age of patients at the time of their self-reported allergic reaction was 20.3 years. The most common allergic symptoms reported in decreasing order of frequency were itchy rash, angioedema, and urticaria. Based on analysis of the questionnaires, 121 patients (63.0%) had probable PCN allergy, 54 (28.1%) had possible PCN allergy, and 17 (8.9%) were unlikely to have a PCN allergy. Fifty-one participants (26.6%) had self-reported subsequent exposure to PCN in their life. This subsequent exposure was well tolerated in 86.3% of the participants. Fifty participants (25.9%) had self-reported subsequent exposure to a first generation cephalosporin and it was well tolerated in 78.4% of them. CONCLUSION: Taking a detailed history from patients with self-reported PCN allergy can help to distinguish a true PCN allergy from a false positive report of allergy and hence allow clinicians to use this important class of antibiotics when truly indicated.

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BACKGROUND: Previous studies have established a correlation between vancomycin troughs and nephrotoxicity. However, data are currently lacking regarding the effect of guideline-recommended weight-based dosing on nephrotoxicity in methicillin-resistant Staphylococcus aureus bacteremia (MRSAB). METHODS: Adults who were at least 18 years of age with methicillin-resistant Staphylococcus aureus bacteremia and received of empiric vancomycin therapy for at least 48 hours (01/07/2002 and 30/06/2008) were included in this multicenter, retrospective cohort study. The association between guideline-recommended, weight-based vancomycin dosing (at least 15 mg/kg/dose) and nephrotoxicity (increase in serum creatinine (SCr) by more than 0.5 mg/dl or at least a 50% increase from baseline on at least two consecutive laboratory tests) was evaluated. Potential independent associations were evaluated using a multivariable general linear mixed-effect model. RESULTS: Overall, 23% of patients developed nephrotoxicity. Thirty-four percent of the 337 patients who met study criteria received weight-based dosing. The cohort was composed of 69% males with a median age of 55 years. The most common sources of MRSAB included skin/soft tissue (32%), catheter-related bloodstream bacteremia (20%), pulmonary (18%). Eighty-six percent of patients received twice daily dosing. Similar rates of nephrotoxicity were observed regardless of the receipt of guideline-recommended dosing (22% vs. 24%, OR 0.91 [95% CI 0.53-1.56]). This finding was confirmed in the multivariable analysis (OR 1.52 [95% CI 0.75-3.08]). Independent predictors of nephrotoxicity were (OR, 95% CI) vancomycin duration of greater than 15 days (3.36, 1.79-6.34), weight over 100 kg (2.74, 1.27-5.91), Pitt bacteremia score of 4 or greater (2.73, 1.29-5.79), vancomycin trough higher than 20 mcg/ml (2.36, 1.07-5.20), and age over 52 years (2.10, 1.08-4.08). CONCLUSIONS: Over one out of five patients in this study developed nephrotoxicity while receiving vancomycin for MRSAB. The receipt of guideline-recommended, weight-based vancomycin was not an independent risk factor for the development of nephrotoxicity.

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BACKGROUND: No studies have evaluated the effect of guideline-recommended weight-based dosing on in-hospital mortality of patients with methicillin-resistant Staphylococcus aureus bacteremia. METHODS: This was a multicenter, retrospective, cohort study of patients with methicillin-resistant Staphylococcus aureus bacteremia receiving at least 48 hours of empiric vancomycin therapy between 01/07/2002 and 30/06/2008. We compared in-hospital mortality for patients treated empirically with weight-based, guideline-recommended vancomycin doses (at least 15 mg/kg/dose) to those treated with less than 15 mg/kg/dose. We used a general linear mixed multivariable model analysis with variables identified a priori through a conceptual framework based on the literature. RESULTS: A total of 337 patients who were admitted to the three hospitals were included in the cohort. One-third of patients received vancomycin empirically at the guideline-recommended dose. Guideline-recommended dosing was not associated with in-hospital mortality in the univariable (16% vs. 13%, OR 1.26 [95%CI 0.67-2.39]) or multivariable (OR 0.71, 95%CI 0.33-1.55) analysis. Independent predictors of in-hospital mortality were ICU admission, Pitt bacteremia score of 4 or greater, age 53 years or greater, and nephrotoxicity. CONCLUSIONS: Empiric use of weight-based, guideline-recommended empiric vancomycin dosing was not associated with reduced mortality in this multicenter study.

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Vancomycin is a commonly used antimicrobial in patients with methicillin-resistant Staphylococcus aureus (MRSA) infections. Increasing vancomycin MIC values in MRSA clinical isolates makes the optimization of vancomycin dosing pivotal to its continued use. Unfortunately, limited data exist regarding the optimal pharmacokinetic-pharmacodynamic (PK-PD) goal to improve bacterial killing and clinical outcomes with vancomycin. The hallmark study in this area suggests that achieving an AUC to MIC ratio of over 400 improves the likelihood of achieving these outcomes. Challenges in the implementation of PK-PD-based dosing for vancomycin include current methodologies utilized in microbiology laboratories, as well as intra- and interpatient pharmacokinetic variability. Individualized dosing based on MIC and specific patient factors is important to achieve optimal outcomes from vancomycin therapy.

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The 2007 Accreditation Council for Pharmacy Education (ACPE) Accreditation Standards and Guidelines for the Professional Program in Pharmacy delineate new expectations for experiential education within curricula and include guidance on the development and conduct of Pharmacy Practice Experiences. The American College of Clinical Pharmacy (ACCP) Educational Affairs Subcommittee C developed a position statement to further delineate the views of ACCP on factors necessary to meet contemporary standards for doctoral education in pharmacy and to provide guidance to our membership on how to implement the new standards. This White Paper provides explanation and supporting documentation for positions on quantitative and qualitative aspects of experiential education, as well as requirements for practice sites, preceptor roles, qualification, credentialing, and development and assessment of student performance.

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Heart failure is a major problem in the Unites States. Despite the availability of and increasing adherence to evidence-based guidelines, the morbidity and mortality from this disease remain significant. Strides have been made in the last several years to develop objective tools to aid in the diagnosis of heart failure and in the prognosis of the affected patients. Brain natriuretic peptide (BNP) and the N-terminal prohormone of BNP are neurohormones released in response to ventricular wall stress and/or tension. As objective laboratory measures, both peptides have similar utility in the treatment of patients with heart failure. Currently, these laboratory tests are approved only to aid in diagnosis. However, data are beginning to emerge that suggest the utility of serial BNP monitoring for the management of chronic heart failure in patients with left ventricular dysfunction. Preliminary studies have shown that when added to traditional management combined with adherence to evidenced-based national guidelines, serial monitoring of BNP levels with adjustment of therapy based on the results may improve outcomes in patients with chronic heart failure compared with traditional clinical management alone. Factors that may limit the use or confound interpretation of the laboratory test results include the effects of demographics (e.g., sex, age, body mass index), concurrent diseases, and drug therapies. Several large, outcomes-based studies are under way to examine the use of serial BNP monitoring to decrease morbidity, mortality, and overall health care costs in patients with heart failure.

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Despite the advent of new antibiotics, resistance in gram-positive pathogens, including staphylococci and enterococci, continues to increase. This is evident with the recent emergence of vancomycin-resistant Staphylococcus aureus . Newer treatment agents are available, including quinupristin-dalfopristin, linezolid, and daptomycin. In addition, investigational agents are being explored. Clinical trials have been conducted for various infections, such as skin and skin structure infections, pneumonia, and bloodstream infections. Antibacterial activity, site of infection, and potential for adverse effects must be taken into account when making decisions regarding therapy.

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