Motivational Interviewing as a Strategy to Impact Outcomes in Heart Failure Patients: A Systematic Review.

BACKGROUND: Heart failure (HF) hospitalization is an expensive healthcare utilization event. Motivational interviewing (MI) has been studied for effects on HF self-management behaviors. OBJECTIVE: The objective of this systematic review was to conduct an exploration and report of evidence and gaps in the literature regarding the impact of MI on HF outcomes. DATA SOURCES: A modified Cochrane systematic review was conducted via a literature search in the MEDLINE, CINAHL, Cochrane Collaborative Systematic Reviews, PsycINFO, Health Source: Nursing/Academic Edition, and Google Scholar databases. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS: Randomized controlled trials (RCTs) or controlled experimental studies published in English from January 1990 to February 2019 that included adults (18 years and older) diagnosed with HF New York Heart Association (NYHA) class I, II, II, or IV were eligible for inclusion. Interventions evaluated were an MI-based face-to-face communication or telephone-based conversation provided by any healthcare provider type. STUDY APPRAISAL AND SYNTHESIS METHODS: The Cochrane method for assessing risk of bias was used to analyze the methodological quality of retained studies. RESULTS: Of 167 initial articles, nine were retained, describing eight unique studies (758 total patients, range 30-241; age range 58-79 years; attrition range 13-36%). The impact of MI was examined for general self-care behaviors (SCBs) (physical activity specifically), quality of life (QoL), and/or hospital readmission prevention. Eight of nine articles reported a positive impact of MI over advice-giving, seven being statistically significant. MI interventions used an initial face-to-face encounter with three to five follow-up telephone encounters. LIMITATIONS: This systematic review had the following limitations: most retained studies included intervention activities conducted in hospital/clinic settings, which limits generalizability of the intervention in other care settings; intervention fidelity, blinding, selection, interventionist training, and random assignment were not clear in all studies; retained studies did not include potential covariates such as health literacy, patient age, and perception of disease/health risks; and some retained studies relied on patient self-report of outcomes, which may introduce recall or social desirability bias. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: MI demonstrated a positive effect on the SCB hospital readmission prevention factor and on QoL. MI delivered with greater frequency and over a longer duration may improve the immediate risk of hospital readmission as well as long-term outcomes through better medication adherence and SCBs. However, heterogeneity in the methods, design, intervention type, and structure challenged comparisons across studies and further research is warranted.

Nebulized Heparin With N-Acetylcysteine and Albuterol Reduces Duration of Mechanical Ventilation in Patients With Inhalation Injury.

OBJECTIVE: Nebulized heparin has been proposed to improve pulmonary function in patients with inhalation injuries. The purpose of this study was to evaluate the impact of nebulized heparin with N-acetylcysteine (NAC) and albuterol on the duration of mechanical ventilation in burn patients. METHODS: This is a retrospective study evaluating mechanically ventilated adult patients admitted to a regional burn center with inhalation injury. Outcomes were compared between patients who were prescribed a combination of nebulized heparin with NAC and albuterol versus similar patients who did not. RESULTS: A total of 48 patients met inclusion criteria (heparin n = 22; nonheparin n = 26). Patients in the nonheparin group had higher percentage of total body surface area (TBSA) burned (29.00 [5.75-51.88] vs 5.25 [0.50-13.25] %TBSA; P = .009), longer duration of mechanical ventilation (6.50 [2.75-17.00] vs 3.00 [1.00-8.25] days; P = .022), and longer intensive care unit length of stay (LOS) (3.00 [3.00-28.75] vs 5.50 days [2.00-11.25]; P = .033). Upon regression, use of heparin was the only variable associated with reducing the duration of mechanical ventilation ( P = .039). CONCLUSION: Nebulized heparin in combination with NAC and albuterol was associated with a significant reduction in the duration of mechanical ventilation.

Assessment of Apixaban Prescribing Patterns for Nonvalvular Atrial Fibrillation in Hospitalized Patients.

BACKGROUND: Apixaban is a direct oral anticoagulant (DOAC) for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (NVAF). Other DOACs require renal dose adjustments based solely on creatinine clearance. Apixaban differs in that its dose adjustments are more complex, potentially leading to prescribing errors. OBJECTIVE: To determine if adherence to Food and Drug Administration (FDA)-approved dosing for apixaban is maintained in hospitalized patients with NVAF. METHODS: Patients ≥18 years old with NVAF who received apixaban during admission to 1 of 3 hospitals were evaluated. The primary outcome was to determine if providers order apixaban in accordance with FDA-approved dosages. Secondary outcomes included determining if pharmacist review increased the number of orders in accordance with FDA-approved dosing, which of the 3 criteria (age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL) were met in patients receiving off-label dosing, and the rationale for off-label prescribing. RESULTS: A total of 556 patients met inclusion criteria. Apixaban was dosed according to FDA labeling by providers in 83.4% (n = 464) of orders. After pharmacist review, 87.0% (n = 484) of orders were at the approved dose, 12.2% (n = 68) were underdosed, and 0.7% (n = 4) were overdosed. Most patients who were underdosed met only 1 dose reduction criterion-most commonly age ≥80 years (56.0%). Reasons for off-label dosing included home dose continuation (39.0%), history of or perceived bleeding risk (30.5%), or unspecified/other (30.5%). CONCLUSIONS: The majority of apixaban orders for NVAF were based on FDA-approved dosages after provider entry and pharmacist review.

Up for Debate: Re-Envisioning the Journal Club with an Article-Centric Student Debate.

Effective utilization of evidence-based medicine requires skillful development of a critical literature evaluation process. Although traditional journal club activities are a common modality to teach and refine these skills, they may limit a learner's motivation to perform a well-rounded critique of primary literature. INNOVATION: In response to the challenges with these traditional formats, we describe a novel approach to refining critical literature evaluation skills in an Advanced Pharmacy Practice Experience (APPE) setting utilizing a focused, article-centric journal club debate. Students, in pairs, are assigned a single article and are tasked with building critical arguments for both pro and con sides of the article, which culminates in a one-on-one debate. KEY FINDINGS: The debate has been well received by students and faculty for increasing engagement in the critical literature evaluation process. The article-centric nature of the debate pushes students to a deeper understanding of an article's merits and pitfalls. Ongoing limitations include significant faculty assessment burden and lack of a standardized, debate-specific evaluation rubric. NEXT STEPS: Future efforts should focus on evaluating student performance and perceptions of the debate compared to traditional journal club formats utilizing pre- and post- surveys. The creation of a debate-specific grading rubric may streamline the evaluation process and reduce faculty assessment burden.

Management of Oral Anticoagulation Therapy After Gastrointestinal Bleeding: Whether to, When to, and How to Restart an Anticoagulation Therapy.

OBJECTIVE: To evaluate current clinical evidence for management of oral anticoagulation therapy after gastrointestinal bleeding (GIB) with an emphasis on whether to, when to, and how to resume an anticoagulation therapy. DATA SOURCES: Relevant articles from MEDLINE, Cochrane Library, and EMBASE databases were identified from 1946 through May 20, 2017, using the keywords: gastrointestinal hemorrhage or gastrointestinal bleeding and antithrombotic therapy or anticoagulation therapy or warfarin or dabigatran or rivaroxaban or apixaban or edoxaban. STUDY SELECTION AND DATA EXTRACTION: All English-language studies assessing management of oral anticoagulation therapy after GIB were evaluated. DATA SYNTHESIS: A total of 9 studies were identified. Four retrospective cohort studies showed that resuming anticoagulation therapy was associated with significantly lower rate of thromboembolism (TE) in the general population. Meta-analyses and prospective cohort studies also supported this finding. Two retrospective cohort studies indicated an increase in GIB when anticoagulation reinitiation occurred in less than 7 days without a decrease in TE. Resuming therapy between 7 and 15 days did not demonstrate a significant increase in GIB or TE. A large retrospective study showed that apixaban was associated with the significantly lowest risk of GIB compared with both rivaroxaban and dabigatran. CONCLUSION: Anticoagulation therapy resumption is recommended, with resumption being considered between 7 and 14 days following GIB regardless of the therapy chosen. Data for warfarin management after GIB should be applied with caution to direct oral anticoagulants (DOACs) because of the quicker onset and experimental nature of reversal agents. Apixaban may be a preferred option when restarting a DOAC therapy.

Dipeptidyl Peptidase-4 Inhibitor-Associated Risk of Bleeding: An Evaluation of Reported Adverse Events.

BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors improve glycemic control, and sitagliptin has been associated with a reduction in cardiovascular events. In vivo data suggest reduced platelet activation, and aggregation may play a role, and therefore, increased bleeding risk is possible. OBJECTIVE: Comparatively assess bleeding risks associated with DPP-4 inhibitors against standard treatment. METHODS: Exploratory analyses of adverse event reports (AERs) from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database (2004-2012 periods) were conducted. DPP-4 inhibitor-related bleeding was assessed with metformin as negative control, and aspirin, clopidogrel, and prasugrel illustrated positive comparators. Reporting odds ratios (RORs) and 95% CIs were calculated as a measure of disproportionality of reporting, and RORs were compared across drugs with the Breslow-Day statistics. RESULTS: From 2004 to 2012, 36 298, 4288, and 1202 AERs were found for sitagliptin, saxagliptin, and linagliptin, respectively, with 863, 102, and 14 bleeding complications. The relative reporting rate was not elevated with any DPP-4 inhibitor (sitagliptin: ROR = 0.71, 95% CI = 0.67-0.76; saxagliptin: ROR = 0.72, 95% CI = 0.59-0.87; linagliptin: ROR = 0.35, 95% CI = 0.20-0.59) or with metformin (ROR = 0.77; 95% CI = 0.75-0.78). Sitagliptin showed relatively higher reporting as compared with linagliptin ( P = 0.006) but not with saxagliptin ( P = 0.98). As positive references, antiplatelet drugs demonstrated relatively higher reporting compared with metformin (aspirin: ROR = 1.50, 95% CI = 1.48-1.51; clopidogrel: ROR = 2.28, 95% CI = 2.23-2.33; prasugrel: ROR = 5.09, 95% CI = 4.57-5.67). CONCLUSION: DPP-4 inhibitors were not associated with an undue increase in bleeding AERs in the FAERS database.

Role of Digoxin in Atrial Fibrillation.

Since its isolation in the 1930s, digoxin has played a pivotal role in the treatment of cardiac conditions including heart failure and supraventricular tachyarrhythmias. The parasympathomimetic activity makes digoxin a reasonable option for controlling ventricular rate in atrial fibrillation (AF). However, the unique pharmacokinetic properties, electrolyte-dependent effects, and P-glycoprotein drug interactions influence the clinical use of digoxin. In addition, the delayed onset and narrow therapeutic index can make digoxin utilization cumbersome and often necessitates serum drug monitoring. Despite digoxin's extensive history, recent literature has cast doubt on the efficacy and safety of this medication in the population with AF. Large amounts of data suggest digoxin offers no benefit on mortality and may increase the risk of mortality though this was not consistent in all evaluations. While robust, the majority of the available studies are not randomized which limits the ability to draw firm conclusions. The potential risk of mortality must be weighed against the expected benefits of digoxin use to make individualized patient care decisions. Clinicians should refrain from utilizing digoxin monotherapy for rate control in AF when other options are viable.

Propofol-associated QTc prolongation.

OBJECTIVES: Propofol is a preferred agent for sedation in patients in the intensive care unit (ICU) due, in part, to its established safety profile. Despite this, recent case reports have suggested a potential for prolongation of the corrected QT interval (QTc) in ICU patients receiving propofol, though limited empirical work has been conducted to evaluate this association. As such, the purpose of this study was to assess the relationship between propofol infusion and QTc prolongation in a historical cohort of ICU patients. METHODS: A single-center, historical, observational, pre-post cohort analysis of medical records from admitted patients ⩾18 years old with cardiovascular disease was conducted, involving cases who received propofol infusion for ⩾3 hours with sequential electrocardiogram monitoring from 2006 to 2012. A multivariable, generalized linear model regression was employed to assess the primary outcome of on-propofol QTc interval (QTc2), controlling for various demographic and clinical factors. RESULTS: A total of 96 patients met inclusion criteria, averaging 56.1 ± 14.1 years of age and 86.1 ± 25.0 kg, with 37.5% being female. A mean prolongation in QTc interval of 30.4 ± 55.5 ms (p < 0.001) was observed during the propofol infusion, with 43.8% of cases exhibiting an on-infusion QTc2 of ⩾ 500 ms. Regression analyses suggested that prolongation in on-propofol QTc was independently associated with baseline QTc interval and amiodarone use, while weight as inversely associated with QTc2 (p < 0.05). CONCLUSION: This historical cohort analysis of adult ICU patients receiving propofol suggests that on-infusion QTc prolongation was associated with increasing baseline QTc interval and with amiodarone use. Further research is needed to evaluate the clinical significance and cause-and-effect relationship between potential QTc changes and propofol use in the ICU.

Pharmacologic management of angioedema induced by angiotensin-converting enzyme inhibitors.

PURPOSE: The published evidence on pharmacologic approaches to the management of angiotensin-converting enzyme inhibitor (ACEI)-induced angioedema is reviewed. SUMMARY: Angioedema is a serious, potentially life-threatening adverse effect of ACEI use. Although the underlying mechanism is not fully understood, excess bradykinin produced through a complex interplay between the kallikrein-kinin and renin-angiotensin-aldosterone systems is thought to play a major role. The nonallergic nature of the reaction renders traditional therapies (corticosteroids and antihistamines) ineffective because those agents do not modify the proposed pathophysiology. Fresh frozen plasma (FFP) provides kinase II, a protein that breaks down bradykinin. Case reports support FFP as a treatment for ACEI-induced angioedema, but no formal evaluations have been completed to date. Both ecallantide and complement 1 esterase (C1) inhibitor concentrate reduce bradykinin production through upstream inhibition of kallikrein. C1 inhibitor concentrate has been used successfully to manage ACEI-induced angioedema in a few reported cases, but robust supportive studies are lacking. Conversely, ecallantide has been evaluated in multiple randomized trials but has not been shown to offer advantages over traditional therapies. The use of icatibant, a direct antagonist of bradykinin B2 receptors, was reported to be beneficial in several case reports and in a small Phase II study, safely and rapidly reducing symptoms of ACEI-induced angioedema. An ongoing Phase III trial (NCT01919801) will better define the role of icatibant in the management of ACEI-induced angioedema. CONCLUSION: FFP, C1 inhibitor, and icatibant appear to be safe and effective therapeutic options for the management of ACEI-induced angioedema, whereas it appears ecallantide should be avoided.