Assessment of Outcomes in Patients with Heart Failure and End-Stage Kidney Disease after Fluid Resuscitation for Sepsis and Septic Shock.

BACKGROUND: Sepsis fluid resuscitation is controversial, especially for patients with volume overload risk. The Surviving Sepsis Campaign recommends a 30-mL/kg crystalloid fluid bolus for patients with sepsis-induced hypoperfusion. Criticism of this approach includes excessive fluid resuscitation in certain patients. OBJECTIVE: The aim of this study was to assess the efficacy and safety of guideline-concordant fluid resuscitation in patients with sepsis and heart failure (HF) or end-stage kidney disease (ESKD). METHODS: A retrospective cohort study was conducted in patients with sepsis who qualified for guideline-directed fluid resuscitation and concomitant HF or ESKD. Those receiving crystalloid fluid boluses of at least 30 mL/kg within 3 h of sepsis diagnosis were placed in the concordant group and all others in the nonconcordant group. The primary outcome was in-hospital mortality. Secondary outcomes included intensive care unit (ICU) and hospital length of stay (LOS); vasoactive medications and net volume over 24 h; new mechanical ventilation, new or increased volume removal, and acute kidney injury within 48 h; and shock-free survival at 7 days. RESULTS: One hundred twenty-five patients were included in each group. In-hospital mortality was 34.4% in the concordant group and 44.8% in the nonconcordant group (p = 0.1205). The concordant group had a shorter ICU LOS (7.6 vs. 10.5 days; p = 0.0214) and hospital LOS (12.9 vs. 18.3 days; p = 0.0163), but increased new mechanical ventilation (37.6 vs. 20.8%; p = 0.0052). No differences in other outcomes were observed. CONCLUSIONS: Receipt of a 30-mL/kg fluid bolus did not affect outcomes in a cohort of patients with mixed types of HF and sepsis-induced hypoperfusion.

Evaluation of Student Academic Performance After Curricular Content Reduction.

OBJECTIVE: To evaluate the effect of curricular content reduction in an integrated course sequence spanning 3 years of a Doctor of Pharmacy curriculum on student examination scores and course grades. METHODS: This 2-year, prepost study compared student overall average and final examination scores and overall course grades after the transition from a 5-day to a 4-day week of an integrated learning experience (ILE) course sequence. In addition, an anonymous, optional 23-item survey was distributed to first to third year pharmacy students asking about the 4-day week change, how they utilized the non-ILE day, and additional demographic and social characteristics to identify factors influencing success on examination and course performance during the 4-day week. RESULTS: There were 533 students included in the overall analysis, with no significant differences in overall course grades in the 5-day vs 4-day week. Examination scores were not significantly different after the transition, except in 2 of 12 courses where scores were higher and final examination scores were not significantly different, except for higher final examination scores in 1 course during the 5-day week. Significant positive influencers of top quartile of examination performance included prepharmacy grade point average ≥ 3.5, age 25 to 29 years, and prepharmacy coursework at the parent institution, whereas using the non-ILE day primarily to sleep negatively influenced outcomes. CONCLUSION: Curricular density is a prevalent problem and addressing it at a program level is essential. Reducing curricular content and hours at our institution did not adversely impact student examination and course performance and slight improvement was noted in some areas.

The Impact of SGLT2 Inhibitors on Cardiovascular Outcomes in Patients With Heart Failure With Preserved Ejection Fraction.

OBJECTIVE: To evaluate the role of sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients with heart failure with preserved ejection fraction (HFpEF). DATA SOURCES: A literature search of PubMed, the Cochrane Library, and Google Scholar databases (January 2015 to June 20, 2023) was performed with keywords: sodium-glucose co-transporter 2 inhibitors OR SGLT2 inhibitors OR bexagliflozin OR canagliflozin OR dapagliflozin OR empagliflozin OR ertugliflozin OR sotagliflozin AND heart failure OR heart failure with preserved ejection fraction, and terms related to CV outcomes including cardiovascular death, hospitalization, hospitalization for heart failure, mortality, death, and major adverse cardiovascular event (MACE). STUDY SELECTION AND DATA EXTRACTION: The reference list from retrieved articles as well as relevant review articles was considered. Pivotal randomized controlled trials and meta-analyses with a primary or secondary end point of CV death or heart failure hospitalization were included. Studies conducted solely in a diabetic patient population were excluded. DATA SYNTHESIS: Dapagliflozin and empagliflozin, in a broad population of heart failure patients including, HFrEF, HFmrEF, HFpEF, and without diabetes, have shown consistent improvement in the combined outcome of CV death and hospitalization for heart failure (HR 0.80, 95% CI 0.73-0.87) and in the reduction of heart failure hospitalizations (HR 0.74, 95% CI 0.67-0.83). In patients with HFpEF, cardiovascular mortality was not demonstrated (HR 0.88, 95% CI 0.77-1.00). Rates of adverse events were low. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Patients with HFpEF and NYHA class II-III with frequent symptoms or hospitalizations for heart failure derive the most benefit from SGLT2 inhibitors with an overall goal of a reduction in heart failure hospitalizations. CONCLUSIONS: The treatment of HFpEF has made progress, but there is still work to be done. Now, SGLT2 inhibitor therapy can be used to further help with symptom control and reduce overall hospitalizations for heart failure.

Direct Oral Anticoagulants for the Treatment of Venous Thromboembolism in Obesity.

Background: Direct oral anticoagulants (DOACs) are known to have similar efficacy with a decreased risk of bleeding when compared to warfarin for the treatment of venous thromboembolism (VTE). In patients with obesity, there are limited data regarding the safety and efficacy of DOACs. Despite concerns for both under- and over-dosing patients with extremes of body weight, there are no dose adjustment recommendations in the package inserts for any of the DOACs. Objective: To evaluate the safety and efficacy of DOACs versus warfarin for the treatment of VTE in patients with obesity. Methods: This single-center, retrospective cohort study included obese patients initiated on DOAC or warfarin therapy for VTE from January 2015 to January 2022. Patients with cancer, hypercoagulable disorders, end-stage kidney disease, or pregnancy were excluded. The primary endpoint was VTE recurrence. Secondary endpoints included major and minor bleeding. Results: A total of 120 patients met criteria for inclusion. Ninety-two received DOAC therapy and 28 received warfarin. The primary endpoint occurred in 4 patients in the DOAC group and 3 patients in the warfarin group (P = 0.35). Major bleeding occurred in 2 patients. Minor bleeding events occurred in 10 (8.33%) patients. Of those, 6 (6.5%) events occurred in patients receiving a DOAC and 4 (14.3%) events occurred in patients receiving warfarin (P = 0.28). Limitations of this study include the retrospective single-center study design. Conclusions: There was a comparable risk of bleeding and recurrent VTE between DOACs and warfarin in patients initiated on therapy for VTE.

Dual Antiplatelet Therapy After an Acute Nonminor Stroke.

Background: In select patients with minor ischemic stroke, dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel is recommended if initiated early and continued for 21 to 90 days. Dual antiplatelet therapy use, in a broader population, has shown to increase the risk of bleeding without an increased antithrombotic benefit. An ongoing area of uncertainty is whether DAPT would benefit the nonminor stroke population when continued for 21 to 90 days.?s. Objective: To describe the effects of DAPT after a nonminor stroke. Methods: This single-center, retrospective cohort study included patients initiated on antiplatelet therapy started within 1 week of symptom onset for a nonminor ischemic stroke from January 2013 to January 2020. Patients with any bleeding disorder or National Institutes of Health Stroke Scale score <4 were excluded. The primary endpoint was major bleeding at 3 months. Secondary endpoints included recurrent stroke and minor bleeding. Results: A total of 158 patients met criteria for inclusion. Ninety (57%) received DAPT, and 68 (43%) received single antiplatelet therapy (SAPT). The primary endpoint occurred in 3 patients in the DAPT group and 1 patient in the SAPT group (P = 0.463). Minor bleeding occurred in 1 patient receiving DAPT and 2 patients receiving SAPT (P = 0.402). There were 10 patients in the DAPT group and 5 patients in the SAPT group who experienced recurrent stroke or transient ischemic attack (P = 0.429). Limitations of this study include the retrospective single-center study design. Conclusion: There was a comparable risk of bleeding and recurrent stroke between DAPT and SAPT in patients admitted with an acute nonminor stroke.

Safety of Nonvitamin K Antagonists Compared with Warfarin in Patients with Atrial Fibrillation and End-Stage Kidney Disease.

OBJECTIVES: This study evaluated the occurrence of major bleeding following the initiation of oral anticoagulation therapy in patients with end-stage kidney disease (ESKD) in a community teaching hospital. METHODS: This was a single-center retrospective study that enrolled patients admitted to the study hospital with ESKD and who received oral anticoagulation (warfarin or nonvitamin K oral antagonists [NOACs]). The primary endpoint was the occurrence of major bleeding at any time while taking oral anticoagulation. Key secondary endpoints included occurrence of minor bleeding, thrombotic events, and hospitalizations because of bleeding or thrombosis. RESULTS: There were 36 patients who received warfarin and 32 patients who received a NOAC. A major bleeding event occurred in 15 of 36 patients (42%) in the warfarin group and in 5 of 32 patients (16%) in the NOAC group (P = 0.032). Hospitalizations as a result of either a bleeding event or a thrombosis occurred in 19 of 36 patients (53%) in the warfarin group and in 8 of 32 patients (25%) in the NOAC group (P = 0.026). The majority of patients in the NOAC group (69%) received a reduced dose for the indication. CONCLUSIONS: Warfarin increased the risk of major bleeding in patients with ESKD compared with NOACs and did not reduce the risk of thrombotic events.

A Review of Direct Oral Anticoagulants in Patients With Stage 5 or End-Stage Kidney Disease.

OBJECTIVE: To evaluate the role of oral anticoagulation in patients with stage 5 chronic kidney disease (CKD-5) or end-stage kidney disease (ESKD). DATA SOURCES: A literature search of PubMed (January 2000 to July 1, 2021), the Cochrane Library, and Google Scholar databases (through April 1, 2021) was performed with keywords DOAC (direct-acting oral anticoagulant) OR NOAC or dabigatran OR rivaroxaban OR apixaban OR edoxaban AND end-stage kidney disease combined with atrial fibrillation (AF) or venous thromboembolism (VTE) OR pulmonary embolism OR deep-vein thrombosis. STUDY SELECTION AND DATA EXTRACTION: Case-control, cohort, and randomized controlled trials comparing DOACs to an active control for AF or VTE in patients with CKD-5 or ESKD and reporting outcomes of stroke, recurrent thromboembolism, or major bleeding were included. DATA SYNTHESIS: Nine studies were included. Efficacy data supporting routine use of warfarin or DOACs in CKD-5 or ESKD are limited. Rivaroxaban and apixaban may provide enhanced safety compared to warfarin in patients with AF. Data for VTE are limited to 1 retrospective study. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Because of the paucity of rigorous, prospective studies in CKD-5 or ESKD, OACs should not be broadly used in this population. It is clear that data regarding efficacy of DOACs cannot be reliably and safely extrapolated from the non-ESKD population. Therefore, use of OACs in this population should be individualized. CONCLUSIONS: If OACs for stroke prevention with AF are deemed necessary, apixaban or rivaroxaban can be considered. DOACs cannot currently be recommended over warfarin in patients with CKD-5 or ESKD and VTE.

Effect of Obesity on Clinical Failure of Patients Treated With ß-Lactams.

BACKGROUND: Altered pharmacokinetics in obese patients raise concerns over worse clinical outcomes. This study assessed whether obese patients receiving a ß-lactam have worse clinical outcomes compared to nonobese patients and to identify if therapeutic drug monitoring may be beneficial. METHODS: This multicenter, retrospective cohort included hospitalized adults admitted from July 2015 to July 2017 treated with a ß-lactam as definitive monotherapy against a gram-negative bacilli for ≥72 hours. Patients were excluded if there was lack of source control or if polymicrobial infections required >1 antibiotic for definitive therapy. Patients were classified based on body mass index (BMI): nonobese (BMI ≤29.9 kg/m2) and obese (BMI ≥30.0 kg/m2). The primary outcome was clinical treatment failure, and secondary outcomes were hospital length of stay, inpatient all-cause mortality, and 30-day all-cause readmission. RESULTS: There were 257 (43.6%) obese patients and 332 (56.4%) nonobese patients included. The most common infections were urinary (50.9%) and respiratory (31.4%). Definitive treatment was driven by third-generation cephalosporins (46.9%) and cefepime (44.7%). Treatment failure occurred in 131 (51%) obese patients and 109 (32.8%) nonobese patients (P < .001). Obesity and respiratory source were independently associated with increased likelihood of treatment failure. Obese patients were hospitalized longer than nonobese patients (P = .002), but no differences were found for all-cause mortality (P = .117) or infection-related readmission (0 = 0.112). CONCLUSIONS: Obese patients treated with ß-lactams have higher rates of treatment failure and longer hospitalization periods than nonobese patients. Future studies are needed to assess the impact of therapeutic drug monitoring and specific dosing recommendations for targeted infection types.

Impact of SGLT2 inhibitors on cardiovascular outcomes in patients with heart failure with reduced ejection fraction.

Heart failure (HF) impacts more than 6 million Americans with an annual mortality rate approaching 22%. Along with optimizing guideline-directed management and therapy (GDMT), the development of treatment options to improve mortality and morbidity in patients with HF with reduced ejection fraction (HFrEF) is paramount. Cardiovascular outcome trials in patients with type 2 diabetes have shown that sodium-glucose cotransporter-2 (SGLT2) inhibitors improve both cardiovascular (CV) and renal outcomes and have consistently reduced hospitalizations for HF in patients with and without a previous history of HF. A precise mechanism by which SGLT2 inhibitors provide benefits for patients with HFrEF has not been identified, and it is probable that multiple pathways may best explain the outcomes seen in recent clinical trials. The mounting evidence that SGLT2 inhibitors reduce HF-related hospitalizations in patients with type 2 diabetes led to the publication of two pivotal trials, the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial and the Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure (EMPEROR-Reduced) trial. Data from these publications demonstrate significant benefit of dapagliflozin and empagliflozin on a variety of CV and HF quality of life end points in patients with HFrEF independent of the presence of type 2 diabetes. Now, widespread application of the clinical findings from the DAPA-HF and EMPEROR-Reduced trials must follow with SGLT2 inhibitors incorporated into GDMT for HFrEF regardless of the presence or absence of diabetes. In this review, we examine key literature surrounding the CV outcome data for SGLT2 inhibitors with a specific focus on patients with HFrEF.

Timing of Anticoagulation in Atrial Fibrillation Status Post Cardioembolic Stroke.

BACKGROUND: Anticoagulation is the mainstay of secondary stroke prevention in patients with atrial fibrillation; however, few studies have assessed the optimal timing for initiation of anticoagulation post cardioembolic stroke. In the 2 weeks following an acute cardioembolic stroke, the risk of recurrent stroke is as high as 8%, but this risk must be balanced against the risk of hemorrhagic transformation with early initiation of anticoagulation. PURPOSE: This study described the time to initiation of anticoagulation and evaluated the in-hospital incidence of hemorrhagic and ischemic complications in 106 patients with atrial fibrillation post an acute cardioembolic stroke. METHODS: A single-center retrospective cohort study was conducted to describe the time to initiation of therapeutic anticoagulation in patients with atrial fibrillation admitted to the hospital for an acute cardioembolic stroke. The primary outcome was the time to initiation of anticoagulation from the time of stroke onset. Secondary outcomes included the incidence of in-hospital hemorrhagic and ischemic complications. RESULTS: The median time to initiation of anticoagulation was 59.5 hours after stroke onset for those who did not receive thrombolytic therapy and 82.6 hours for those who did received thrombolytic therapy. Out of 100 patients initiated on anticoagulation, no ischemic complications were observed. Four patients experienced a hemorrhagic conversion following initiation of anticoagulation. In 3 of these patients, anticoagulation was initiated within 48 hours of stroke onset. CONCLUSION: A small percentage of patients experienced an in-house hemorrhagic conversion when anticoagulation was initiated between 48 hours and 7 days.

Frequency of ß-Blocker Use Following Exacerbations of COPD in Patients with Compelling Indication for Use.

OBJECTIVE: To assess the current use of ß-blockers in patients with compelling indications for use, following the acute exacerbation of chronic obstructive pulmonary disease (COPD). METHODS: We performed a multicenter retrospective observational study using data from all of the patients admitted to five institutions for an acute exacerbation of COPD. Patients were included if they were admitted for an acute exacerbation of COPD and had a compelling indication for the use of a ß-blocker, defined as previous myocardial infarction or heart failure with left ventricular ejection fraction ≤40%. RESULTS: There were 396 patients meeting the criteria for inclusion in the study. The population was predominantly white men with myocardial infarction as the most prevalent compelling indication. On admission, 267 (67.4%) patients were receiving ß-blockers, which increased to 278 (70.2%) at discharge. There were 118 (29.8%) patients discharged without ß-blockers. Of the predictors tested, none were significantly predictive of a patient not receiving ß-blockers upon discharge; however, home and in-hospital ß-blockers reduced the likelihood of being discharged without a ß-blocker. Of the 129 patients not receiving ß-blockers prehospitalization, 23 (17.8%) were discharged with a new prescription for a ß-blocker. CONCLUSIONS: Nearly one-third of patients with compelling indications for ß-blockers were not prescribed the therapy at discharge.

Innovative utilization of pharmacist-led board review in a family medicine residency curriculum.

BACKGROUND AND PURPOSE: The Society of Teachers of Family Medicine Group on Pharmacotherapy recommends a formal curriculum during family medicine residency training and describes benefits of utilizing pharmacists. Limited literature exists on how programs have incorporated questions from family medicine board preparation sources into pharmacotherapy academic education. The primary objective was to assess the impact on family medicine residents' perceived knowledge after incorporation of board review items into pharmacotherapy sessions. EDUCATIONAL ACTIVITY AND SETTING: Pharmacists affiliated with the University of Alabama Family Medicine Residency program incorporated questions from board preparation sources into monthly interactive pharmacotherapy sessions as part of a didactic curriculum between 2014 and 2016. An anonymous survey was administered for two consecutive years in 2015 and 2016 to assess residents' perceptions of the sessions and utilization of board-type questions as an active learning component. The change in residents' perception of knowledge was quantitatively analyzed and written comments were evaluated for recurring themes. FINDINGS: The cumulative survey response was 78% (68/87). Over 80% of residents reported that pharmacotherapy sessions and the use of board-type questions was quite or very helpful. The percent of residents that rated their knowledge as good or excellent significantly increased after every session compared to baseline. Residents noted the sessions' information, applicability, interactive nature, and relevance as strengths. SUMMARY: Incorporation of board preparation questions into interactive pharmacotherapy sessions was well received and improved residents' perception of pharmacotherapy knowledge. Utilizing this model in a formal pharmacotherapy curriculum taught by pharmacists is beneficial for family medicine resident learners.

Evaluation of a Pharmacist-Specific Intervention on 30-Day Readmission Rates for High-Risk Patients with Pneumonia.

BACKGROUND: Pharmacist interventions have been shown to have an impact on reducing readmission rates, however further research is necessary to target resources to high-risk populations and determine the most effective bundle of interventions. OBJECTIVE: To evaluate the effect of a pharmacist-bundled intervention on 30-day readmission rates for high-risk patients with pneumonia. METHODS: A pilot study with a historical control conducted at a community, teaching-affiliated medical center. Up to 65 selected subjects were included if they had pneumonia and any of the following high-risk criteria: admission within 6 months, at least 5 scheduled home medications, chronic obstructive pulmonary disease (COPD), or heart failure. A retrospective chart review was conducted to compile the historical control group that received usual care between June and November 2013. Patients admitted from December 2013 through March 2014 were reviewed to receive a bundled intervention. The primary outcome was 30-day readmission rates. Risk factors and reasons for readmission, pharmacist clinical interventions, and the time interval between discharge and readmission were also evaluated. RESULTS: A trend toward a reduced 30-day readmission rate was observed in the intervention group (n = 43) compared to those who received usual care (n = 65) (27.9% vs 40.0%; relative risk [RR], 0.6977; 95% CI, 0.3965-1.2278; P = .2119). The most commonly identified high-risk inclusion criteria were having at least 5 scheduled home medications and COPD. The time interval between discharge and readmission did not considerably differ between groups (10.8 vs 10.6 days). CONCLUSIONS: The pharmacist-bundled intervention was associated with a reduced 30-day readmission rate for high-risk patients with pneumonia.

Corticosteroids in the treatment of acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic and progressive disease that affects an estimated 10% of the world's population over the age of 40 years. Worldwide, COPD ranks in the top ten for causes of disability and death. Given the significant impact of this disease, it is important to note that acute exacerbations of COPD (AECOPD) are by far the most costly and devastating aspect of disease management. Systemic steroids have long been a standard for the treatment of AECOPD; however, the optimal strategy for dosing and administration of these medications continues to be debated. OBJECTIVE: To review the use of corticosteroids in the treatment of acute exacerbations of COPD. MATERIALS AND METHODS: Literature was identified through PubMed Medline (1950-February 2014) and Embase (1950-February 2014) utilizing the search terms corticosteroids, COPD, chronic bronchitis, emphysema, and exacerbation. All reference citations from identified publications were reviewed for possible inclusion. All identified randomized, placebo-controlled trials, meta-analyses, and systematic reviews evaluating the efficacy of systemic corticosteroids in the treatment of AECOPD were reviewed and summarized. RESULTS: The administration of corticosteroids in the treatment of AECOPD was assessed. In comparison to placebo, systemic corticosteroids improve airflow, decrease the rate of treatment failure and risk of relapse, and may improve symptoms and decrease the length of hospital stay. Therefore, corticosteroids are recommended by all major guidelines in the treatment of AECOPD. Existing literature suggests that low-dose oral corticosteroids are as efficacious as high-dose, intravenous corticosteroid regimens, while minimizing adverse effects. Recent data suggest that shorter durations of corticosteroid therapy are as efficacious as the traditional treatment durations currently recommended by guidelines. CONCLUSION: Systemic corticosteroids are efficacious in the treatment of AECOPD and considered a standard of care for patients experiencing an AECOPD. Therefore, systemic corticosteroids should be administered to all patients experiencing AECOPD severe enough to seek emergent medical care. The lowest effective dose and shortest duration of therapy should be considered.

Assessment and revision of clinical pharmacy practice internet web sites.

BACKGROUND: Health care professionals, trainees, and patients use the Internet extensively. Editable Web sites may contain inaccurate, incomplete, and/or outdated information that may mislead the public's perception of the topic. OBJECTIVE: To evaluate the editable, online descriptions of clinical pharmacy and pharmacist and attempt to improve their accuracy. METHODS: The authors identified key areas within clinical pharmacy to evaluate for accuracy and appropriateness on the Internet. Current descriptions that were reviewed on public domain Web sites included: (1) clinical pharmacy and the clinical pharmacist, (2) pharmacy education, (3) clinical pharmacy and development and provision for reimbursement, (4) clinical pharmacists and advanced specialty certifications/training opportunities, (5) pharmacists and advocacy, and (6) clinical pharmacists and interdisciplinary/interprofessional content. The authors assessed each content area to determine accuracy and prioritized the need for updating, when applicable, to achieve consistency in descriptions and relevancy. The authors found that Wikipedia, a public domain that allows users to update, was consistently the most common Web site produced in search results. RESULTS: The authors' evaluation resulted in the creation or revision of 14 Wikipedia Web pages. However, rejection of 3 proposed newly created Web pages affected the authors' ability to address identified content areas with deficiencies and/or inaccuracies. CONCLUSIONS: Through assessing and updating editable Web sites, the authors strengthened the online representation of clinical pharmacy in a clear, cohesive, and accurate manner. However, ongoing assessments of the Internet are continually needed to ensure accuracy and appropriateness.

Evaluation of vancomycin and gentamicin dialysis clearance using in vivo and in vitro systems.

Advances in hemodialysis (HD) techniques have increased the potential for drug removal. Quantifying drug clearance in clinical studies for all possible dialysis conditions is impractical, given the variability in dialysis conditions. The purpose of this study was to determine the dialysis clearance (CL(D)) of vancomycin and gentamicin using in vitro and in vivo methods and evaluate the applicability of in vitro data. In vitro dialysis was used to determine the CL(D) of vancomycin and gentamicin under conditions of intermittent HD (IHD) and sustained low-efficiency dialysis (SLED). Two Fresenius polysulfone dialyzers were studied: F180NR for IHD and F50 for SLED. Data were compared with in vivo CL(D) determined in patients with end-stage renal disease receiving IHD and from the literature for SLED. Under IHD conditions, in vitro CL(D) of vancomycin and gentamicin was 131 ± 3 and 154 ± 3 mL/min, respectively, and under SLED condition it was 72 ± 9 and 84 ± 11 mL/min, respectively. These values were 11-27% higher than in vivo CL(D) for IHD (103 ± 15 mL/min for vancomycin and 132 ± 25 mL/min for gentamicin) and SLED (63 mL/min for vancomycin and 76 ± 38 mL/min for gentamicin). There was a statistically significant difference in vancomycin clearance by IHD for the in vitro study compared with in vivo data (p = 0.012), but not for gentamicin (p = 0.18). In vitro methods overestimated in vivo CL(D), but are reasonable to assist with drug regimen design if one considers the limitations.

Roflumilast: a phosphodiesterase-4 inhibitor for the treatment of severe chronic obstructive pulmonary disease.

BACKGROUND: Roflumilast is a newly approved phosphodiesterase-4 inhibitor for the treatment of severe chronic obstructive pulmonary disease (COPD) associated with chronic bronchitis and a history of exacerbations. OBJECTIVE: The objective of this article is to review the pharmacology, clinical efficacy, and tolerability of roflumilast in the treatment of COPD. METHODS: Articles were identified using MEDLINE (1966-August 1, 2011) and EMBASE (1947-August 1, 2011). Searches were conducted using the terms roflumilast and COPD. Included in the search were all English-language clinical trials that were randomized, had durations of >6 weeks, and studied the effects of roflumilast on the forced expiratory volume in 1 second (FEV(1)) or rates of exacerbations in patients with COPD. Abstracts from the annual meetings of the American Thoracic Society, American College of Chest Physicians, and European Respiratory Society were also searched to identify relevant publications. In addition, all pertinent studies evaluating the pharmacokinetics and pharmacodynamics of roflumilast were included. RESULTS: A total of 6 clinical trials (4 publications) evaluating the efficacy of roflumilast were identified and included. For the treatment of COPD, roflumilast was associated with a significant improvement in lung function (increase in FEV(1) of 36-88 mL) when compared with placebo. Roflumilast also reduced the rate of exacerbations in subsets of patients with chronic cough and a history of exacerbations. Overall, health-related quality of life was not significantly affected. Adverse effects were common in clinical trials, with 9% to 16% of patients discontinuing therapy as a result. The most frequently reported adverse effects were gastrointestinal issues, headache, and weight loss. Suicide-related adverse effects have occurred in 5 patients receiving roflumilast and 1 patient receiving placebo. CONCLUSION: Roflumilast significantly improved FEV(1) in clinical trials but had inconsistent reductions in the rates of exacerbations. Comparative studies with recommended therapies for COPD, particularly inhaled corticosteroids, are needed to better assess the role of roflumilast in the management of COPD.

Use of conivaptan for the treatment of symptomatic hyponatremia in a patient with acute decompensated heart failure.

PURPOSE: The successful use of conivaptan for the treatment of symptomatic hypervolemic hyponatremia in a patient with acute decompensated heart failure is reported. SUMMARY: A 67-year-old woman with severe ischemic dilated cardiomyopathy was admitted to the hospital due to a heart failure exacerbation. She was initially managed with furosemide and milrinone, but her condition continued to worsen. By hospital day 10, her serum sodium concentration had decreased to 114 meq/L. A 96-hour trial of conivaptan was initiated, and the patient's serum sodium concentration increased to 125 meq/L, blood urea nitrogen level decreased from 34 to 15 g/dL, serum creatinine concentration decreased from 1.1 to 0.9 g/dL, and fluid balance was -9800 mL. After completion of the 96-hour trial of conivaptan, the patient quickly decompensated. Conivaptan was restarted three days later; again, the patient's sodium level quickly increased, and aquaresis occurred. By hospital day 24, the patient was stable enough to undergo a cardiac catheterization, and a stent was placed. On day 26, the patient died while being prepared for an upgrade to a biventricular implantable cardioverter defibrillator. Multiple trials have evaluated conivaptan for the treatment of heart failure. Conivaptan improves hyponatremia and hemodynamic parameters acutely and increases urine output but has failed to show improvement in heart failure symptoms in the published literature. No adverse cardiac effects resulted from the use of conivaptan in this patient. CONCLUSION: Treatment with i.v. conivaptan in a patient with symptomatic hyponatremia and acute decompensated heart failure resulted in marked diuresis and improvement of hyponatremia.

Tolvaptan: a vasopressin antagonist for the management of euvolemic and hypervolemic hyponatremia.

Tolvaptan is a new vasopressin antagonist developed for the treatment of hypervolemic or euvolemic hyponatremia. It has greater affinity for the V(2) receptor than native vasopressin or any other vasopressin antagonist. Blockade of the V(2) receptor induces solute-free water excretion without affecting normal electrolyte excretion. The pharmacokinetics and pharmacodynamics of tolvaptan are suitable for once-daily dosing. Throughout all phases of clinical studies, it was shown to be safe for short- and long-term use. Tolvaptan effectively increases serum sodium levels in patients with heart failure, cirrhosis and syndrome of inappropriate secretion of antidiuretic hormone. In patients hospitalized owing to heart failure, tolvaptan decreased bodyweight, increased urine output and improved dyspnea compared with placebo. However, tolvaptan has not proven to be beneficial for the long-term management of heart failure. Currently, tolvaptan is the only oral agent in its class available in the USA and Europe.

Treatment of warfarin-related intracranial hemorrhage: a comparison of prothrombin complex concentrate and recombinant activated factor VII.

OBJECTIVE: Warfarin-related intracranial hemorrhage (ICH) is a devastating complication of warfarin therapy. Several studies have demonstrated successful correction of the international normalized ratio (INR) using prothrombin complex concentrate (PCC) or recombinant activated factor VII (rFVIIa). To our knowledge, no study has directly compared these agents for treatment of warfarin-related ICH. METHODS: We retrospectively reviewed the charts of 15 patients who received rFVIIa and 9 who received PCC for treatment of warfarin-related ICH over a 2-year period. The primary objective was to compare the efficacy of rFVIIa and PCC in correcting the INR to 1.3 or less. Baseline INR was compared to INR obtained within 1, 3, 6, 12, and 24 hours after rFVIIa or PCC administration. RESULTS: Six patients in the rFVIIa group and five in the PCC group had a follow-up INR within 1 hour of agent administration. In the rFVIIa group, the mean INR decreased from 6.1 to 1.1 and from 2.3 to 1.48 in the PCC group. At 6 hours, all rFVIIa patients and six (67%) PCC patients had at least one subsequent INR, with 93% and 50% correcting to an INR of 1.3 or less. Mean dose for all patients included was 53.4 ± 17.5 µg/kg and 27.8 ± 15.4 units/kg for rFVIIa and PCC, respectively. CONCLUSION: Correction of the INR is more reliably obtained with rFVIIa when compared to PCC. Larger, prospective studies comparing these therapies for warfarin-related ICH are needed.