Mechanisms of landiolol-mediated positive inotropy in critical care settings.

PURPOSE: To present the potential mechanisms by which landiolol enhances a positive inotropic response in critically ill patients. METHODS: Analysis of preclinical, animal, and clinical data to provide novel knowledge and translate research findings into potential clinical application. RESULTS: The super-selective ß1-antagonist landiolol may increase inotropy and may be associated with positive outcomes in critically ill patients with acute decompensated heart failure or sepsis. CONCLUSION: This review sheds light on the potential mechanisms by which landiolol enhances a positive inotropic response, potentially alleviating the long-held concern over possible negative hemodynamic effects in critically ill patients.

Metoprolol vs. diltiazem in the acute management of atrial fibrillation in patients with heart failure with reduced ejection fraction.

OBJECTIVE: The objective of this study was to examine the effects of metoprolol versus diltiazem in the acute management of atrial fibrillation (AF) with rapid ventricular response (RVR) in patients with heart failure with reduced ejection fraction (HFrEF). METHODS: This retrospective cohort study of patients with HFrEF in AF with RVR receiving either intravenous push (IVP) doses of metoprolol or diltiazem was conducted between January 2012 and September 2016. The primary outcome was successful rate control within 30 min of medication administration, defined as a heart rate (HR) < 100 beats per minute or a HR reduction ≥ 20%. Secondary outcomes included rate control at 60 min, maximum median change in HR, and incidence of hypotension, bradycardia, or conversion to normal sinus rhythm within 30 min. Signs of worsening heart failure were also evaluated. RESULTS: Of the 48 patients included, 14 received metoprolol and 34 received diltiazem. The primary outcome, successful rate control within 30 min, occurred in 62% of the metoprolol group and 50% of the diltiazem group (p = 0.49). There was no difference in HR control at predefined time points or incidence of hypotension, bradycardia, or conversion. Although baseline HR varied between groups, maximum median change in HR did not differ. Signs of worsening heart failure were similar between groups. CONCLUSIONS: For the acute management of AF with RVR in patients with HFrEF, IVP diltiazem achieved similar rate control with no increase in adverse events when compared to IVP metoprolol.

The association of elevated trough serum vancomycin concentrations with obesity.

BACKGROUND: Obese patients display differences in vancomycin drug disposition, which may complicate attainment of appropriate serum vancomycin concentrations (SVCs). This study was conducted to determine if obesity leads to trough SVCs above the therapeutic range. METHODS: This retrospective cohort study sought to determine the rate and predictors of high (i.e. >20 mg/L) serum trough levels according to level of obesity. RESULTS: Increasing BMI predicted SVCs > 20 mg/L after controlling for dose, age, and serum creatinine. Obese patients had significantly higher mean trough SVCs compared to non-obese patients (16.5 mg/L vs 12.1 mg/L, p = 0.004) and a significantly higher proportion of obese patients had trough SVCs > 20 mg/L (18.9% vs 4.2%, p = 0.03). CONCLUSION: Increasing obesity predicted higher probabilities of SVCs > 20 mg/L. Development of alternative dosing and management strategies for vancomycin may be necessary to account for pharmacokinetic changes associated with obesity.

Implementation of a Student Pharmacist-Led Program to Enhance Health Access in an Arab-American Community Head: Health Program in an Arab-American Community.

Objectives: Immigration of Arabs to the United States has increased in recent years due to political instability and need for improved access to healthcare. Cardiovascular disease, diabetes, and obesity disproportionally affect Arab Americans. Student pharmacists are well positioned to increase health awareness by providing health screening services and education classes to the Arab immigrant community. This report will describe the development of a student-run Arab American Health Awareness Program (AAHAP) that provides culturally-sensitive community screening services targeting common health disparities seen among Arab-Americans. Design: Data were collected on the number of patient cardiometabolic screenings, referrals for medical care, and health classes which were performed over the course of 2 years. The practice setting included community centers, faith-based centers, and grocery stores in the Chicago area participating in the AAHAP. Results: Over the course of two years, eight cardiometabolic screenings and four community health classes were provided to the Arab-American community. Over 100 student pharmacists provided screenings to 929 patients through AAHAP. Twenty percent (n=193) of all patients screened were referred for further medical care. A total of 77% patients were within goal for blood pressure, 82.3% for blood glucose, and 39.4% for BMI. Patients with a known history of hypertension (n=83) or diabetes (n=64) were more likely to have uncontrolled blood pressure (45% vs 11%, p<0.05) or blood glucose (39% vs 14%, p<0.05) compared to patients without a history of these chronic conditions. Conclusion: Student pharmacists can be drivers for health access through community health programs for ethnically minoritized populations. Development of a health awareness program focused on known health disparities in Arab Americans has provided student pharmacists with opportunities to deliver culturally-sensitive care and medical referral services to an underserved community.

Considerations for select transitions of care for people with HIV: adolescent to adult, prison to society and the postpartum period.

Proper transitions of care for people with HIV (PWH) are necessary to ensure continuity of care, medication adherence and maintenance of successful clinical outcomes. Three transitions of care may lead to suboptimal outcomes if PWH are not correctly engaged: adolescent to adult, prison to society and the postpartum period. The management of these care transitions is a vital part of engagement in treatment. Evidence highlighting the gaps in care transitions provides a potential framework to optimize outcomes for PWH.

Low incidence of renal impairment observed in tenofovir-treated patients.

OBJECTIVES: To compare the incidence of renal impairment in HIV-infected patients exposed versus unexposed to tenofovir and to characterize risk factors associated with renal impairment. METHODS: We undertook a retrospective cohort and nested case-control study of 514 Northwestern University HIV Outpatient Study participants who received antiretroviral therapy (ART) between 1 August 2001 and 31 July 2007. Renal impairment was defined as meeting at least one of two validated criteria based on serum creatinine, calculated glomerular filtration rate and creatinine clearance. Multivariable analysis was performed to identify risk factors for renal impairment. RESULTS: Renal impairment occurred in 14% (n = 72) of the cohort and was not correlated with exposure to tenofovir in univariate analyses. In multivariable analysis, more advanced age [odds ratio (OR) = 1.04, P = 0.02], diabetes (OR = 3.6, P < 0.01), decreased weight (OR = 0.97, P = 0.02) and endpoint CD4 ≤200 cells/mm(3) (OR = 2.5, P = 0.03) were positive predictors of renal impairment; tenofovir exposure (OR = 0.41, P = 0.01) was negatively correlated with renal impairment. CONCLUSIONS: Tenofovir-containing ART was associated with less renal impairment than ART without tenofovir in a patient cohort with a high incidence of renal impairment. Chronic co-morbid conditions known to be associated with renal impairment should be excluded prior to attributing renal impairment to tenofovir.

Quantitative analysis of early chemically-induced pulmonary lesions in mice of varying susceptibilities to lung tumorigenesis.

Inbred mice vary in their susceptibility to develop macroscopic, chemically-induced, pulmonary neoplasias. It is not known, however, whether microscopic lesions appear in resistant strains but do not grow or if no early lesions arise at all. We show herein that resistant C57BL/6J (B6) and intermediately resistant BALB/cByJ (BALB) mice form very few urethane-induced early microadenomas (i.e. adenomas larger than hyperplasic foci, but detectable only by light microscopy). Additionally, while all urethane-induced microadenomas in sensitive A/J mice gave rise to adenomas, most microscopic tumors induced in BALB mice by 2-stage, 3-methylcholanthrene/butylated hydroxytoluene carcinogenesis spontaneously regressed. The formation of microscopic lesions is thus genetically dependent, but whether they continue to grow or regress depends on how they were induced.

Pharmacokinetics of centhaquin citrate in a dog model.

OBJECTIVES: Centhaquin citrate is a novel agent that is being developed for use in the resuscitation of patients with haemorrhagic shock. While pharmacokinetics have been described in small animal models, the pharmacokinetic parameters of centhaquin citrate in large mammals have yet to be described. METHODS: Four healthy Beagle dogs (two males and two females) were given an intravenous bolus of 1.0 mg/kg centhaquin citrate. Plasma concentrations were measured at baseline and at ten time points within 24 h after administration. Multiple compartmental models were built and compared. The nonparametric adaptive grid function within the Pmetrics package for R was used for parameter estimation. Predicted concentrations were calculated using population mean and individual Bayesian posterior parameters. KEY FINDINGS: Centhaquin citrate pharmacokinetic parameters were best described using a two-compartment model. Median (IQR) values for Ke , Vc , Vp , Kcp and Kpc were 4.9 (4.4-5.2) h(-1) , 328.4 (304.0-331.9) l, 1000.6 (912.3-1042.4) l, 10.6 (10.3-11.1) h(-1) and 3.2 (2.9-3.7) h(-1) , respectively. CONCLUSIONS: Pharmacokinetic parameters of centhaquin citrate in a large mammal have been described. A large volume of distribution and rapid elimination were observed, consistent with previous work in rats.

Empiric antibiotic selection for infectious emergencies: bacterial pneumonia, meningitis and sepsis.

Appropriate early management of infectious emergencies is essential to preventing adverse outcomes. Clinicians in acute-care settings must be prepared to provide appropriate empiric antibiotics, as failure to do so has been associated with an increased risk of mortality. Empiric treatment of these infections requires knowledge of the disease state, most common pathogens, and patient-specific risk factors. Additionally, regional and institutional patterns of antibiotic resistance must be taken into consideration. At the same time, inappropriate use of broad-spectrum antibiotics should be avoided to prevent emergence of antimicrobial resistance. It is also essential that initial antibiotic therapy be de-escalated and redirected once the causative pathogen has been identified and antibiotic susceptibilities determined. Bacterial infection with pneumonia, meningitis and sepsis severe enough to warrant hospitalization are included in this review. The most common bacterial pathogens and empiric antibiotic recommendations for immunocompetent adults will be discussed. In addition, circumstances that may influence the selection of certain antibiotics are reviewed.