Leslie A. Hamilton

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.

Increased hypoglycemia associated with renal failure during continuous intravenous insulin infusion and specialized nutritional support

OBJECTIVE To evaluate glycemic control for critically ill, hyperglycemic trauma patients with renal failure who received concurrent intensive insulin therapy and continuous enteral nutrition (EN) or parenteral nutrition (PN). METHODS Adult trauma patients with renal failure who were given EN or PN concurrently with continuous graduated intravenous regular human insulin (RHI) infusion for at least 3 d were evaluated. Our conventional RHI algorithm was modified for those with renal failure by allowing greater changes in blood glucose (BG) concentrations before the infusion rate was escalated. BG concentration was determined every 1 to 2 h while receiving the insulin infusion. BG control was evaluated on the day before RHI infusion and for a maximum of 7 d while receiving RHI. Target BG during the RHI infusion was 70 to 149 mg/dL (3.9 to 8.3 mmol/L). Glycemic control and incidence of hypoglycemia for those with renal failure were compared with a historical cohort of critically ill, hyperglycemic trauma patients without renal failure given our conventional RHI algorithm. RESULTS Twenty-one patients with renal failure who received the modified RHI algorithm were evaluated and compared with 40 patients without renal failure given our conventional RHI algorithm. Average BG concentration was significantly greater for those with renal failure (133±14 mg/dL or 7.3±0.7 mmol/L) compared with those without renal failure (122±15 mg/dL or 6.8±0.8 mmol/L), respectively (P<0.01). Patients with renal failure showed worsened glycemic variability, with 16.1±3.3 h/d within the target BG range, 6.9±3.2 h/d above the target BG range, and 1.4±1.1 h/d below the target BG range compared with 19.6±4.7 h/d (P<0.001), 3.4±3.0 h/d (P<0.001), and 0.7±0.8 h/d (P<0.01) for those without renal failure, respectively. Moderate hypoglycemia (<60 mg/dL or<3.3 mmol/L) occurred in 76% of patients with renal failure compared with 35% without renal failure (P<0.005). Severe hypoglycemia (BG<40 mg/dL or<2.2 mmol/L) occurred in 29% of patients with renal failure compared with none of those without renal failure (P<0.001). CONCLUSION Despite receiving a modified RHI infusion, critically ill trauma patients with renal failure are at greater risk for developing hypoglycemia and have more glycemic variability than patients without renal failure.

Treatment of methicillin-resistant Staphylococcus aureus ventilator-associated pneumonia with high-dose vancomycin or linezolid.

BACKGROUND The purpose of this study was to determine the clinical cure rate of high-dose vancomycin for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) ventilator-associated pneumonia (VAP) in critically ill trauma patients. Recent trials suggest that a traditional dose of 1 g q12 hours results in unacceptable cure rates for MRSA VAP. Thus, more aggressive vancomycin dosing has the potential to improve efficacy. Based on pharmacokinetic principles, the goal initial dose at the study center has been 20 mg/kg q12 hours or q8 hours since the 1990s. METHODS All patients admitted to the trauma intensive care unit from 1997 to 2008 diagnosed with MRSA VAP were retrospectively reviewed. Diagnosis required bacterial growth ≥100,000 colony forming units/mL from a bronchoscopic bronchoalveolar lavage, new or changing infiltrate, plus at least two of the following: fever, leukocytosis or leukopenia, or purulent sputum. RESULTS Overall, 125 patients with 141 episodes of MRSA VAP were identified. Mean age was 47 years ± 21 years, median Injury Severity Score was 29 (22–43), 70% of patients were male, and the mean length of intensive care unit stay was 38 days ± 35 days. The mean initial vancomycin dose was 18.1 mg/kg/dose with a mean duration of therapy of 11 days. Clinical success was achieved in 88% (125 of 131) of episodes, with microbiological success in 89% (66 of 74) of episodes with a follow-up bronchoscopic bronchoalveolar lavage. Overall mortality was 20% (25 of 125), with death due to VAP in 12 of 25 deaths. Mean initial vancomycin trough concentrations were 10.6 mg/L in the clinical success group and 13.3 mg/L in the clinical failure group (p = not significant). CONCLUSIONS High-dose vancomycin provided an acceptable cure rate for MRSA VAP in critically ill trauma patients. LEVEL OF EVIDENCE Therapeutic study, level III.

Risk of cancer in patients receiving insulin glargine

PURPOSE The risk of malignancy in patients using insulin glargine was evaluated. SUMMARY Patients with diabetes mellitus have increased rates of cancers including breast, colon, and pancreatic cancers. Since nondiabetic patients with increased levels of insulin have similar rates of the same cancers, hyperinsulinemia could be key. Normally, insulin produces metabolic effects and insulin-like growth factor-I (IGF-I) produces mitogenic effects. Since the molecules are structurally similar, it is possible for insulin to act like IGF-I, promoting mitogenicity. Concern that insulin may promote the growth of some cancers is heightened with insulin analogues, since changing the structure of human insulin could produce molecules with increased mitogenic potential. In vivo, insulin glargine has been shown to have greater mitogenic potential than human insulin. It is unknown whether this occurs in vitro, because the insulin glargine molecule is transformed once injected. Studies published in 2009 suggest that patients on insulin glargine could be at greater risk for cancer than patients on other antidiabetes therapies, but the trial results are conflicting. In response, the Food and Drug Administration, American Diabetes Association, American Association of Clinical Endocrinologists, and European Association for the Study of Diabetes have formally stated that patients should continue to use insulin glargine until more information is available. CONCLUSION Studies on the relationship between insulin glargine and cancer have been inconclusive.

Risk factors for discharge on a new antipsychotic medication after admission to an intensive care unit

PURPOSE Increased awareness of delirium in the intensive care unit (ICU) has led to higher use of antipsychotic medications for treatment of delirium. These medications are often not discontinued at ICU or hospital discharge, which may increase the risk of inappropriate polypharmacy. Our study sought to identify risk factors for being discharged on a new antipsychotic medication after admission to a trauma-surgical ICU or neurocritical care unit. METHODS This was a retrospective cohort study at an academic medical center and included patients who were admitted to the trauma-surgical ICU or neurocritical care unit and received an antipsychotic medication. Those younger than 18 years, died before hospital discharge, or did not have complete documentation were excluded. RESULTS A total of 341 records were included in the final analysis. Of those, 82 (24%) were discharged on a new antipsychotic and 67% of those patients had no documented indication. Acute Physiology and Chronic Health Evaluation II (odds ratio, 1.030 [95% confidence interval, 1.030-1.110]) and days treated with benzodiazepines (odds ratio, 1.101 [95% confidence interval, 1.060-1.143]) were independently associated with being discharged on a new antipsychotic medication. CONCLUSIONS Those patients with higher Acute Physiology and Chronic Health Evaluation II scores and more benzodiazepine days are at increased odds of being discharged on a new antipsychotic.

Management of Apixaban-associated Subdural Hematoma: A Case Report on the Use of Factor Eight Inhibitor Bypassing Activity

Objective:We report a case of a patient receiving apixaban who developed a spontaneous subdural hematoma and declining mental status that improved after administration of a single dose of factor eight inhibitor bypassing activity. Design:Case report. Setting:Comprehensive Stroke Center, Neurocritical Care Unit. Patient:A 76-year-old man presented to an outside facility with a chief complaint of headache and pain behind his right eye. A CT scan of his head revealed a subdural hematoma. The patient was transferred to our facility with worsening clinical status. Interventions:After a confirmatory cranial CT scan revealed a worsening subdural hematoma with midline shift, a single dose of factor VIII inhibitor bypassing activity (25 U/kg) was administered. Measurements and Main Results:Coagulation tests following the administration of factor VIII inhibitor bypassing activity and a follow-up CT scan confirmed hemostasis. The patient was discharged home with no focal deficits. Conclusions:Factor VIII inhibitor bypassing activity may be a viable, nonspecific reversal agent for life-threatening bleeding associated with apixaban.

Nebivolol for the treatment of heart failure

PURPOSE. The pharmacology, pharmacokinetics, efficacy, safety, and place in therapy of nebivolol are reviewed. SUMMARY. Nebivolol, a third-generation, highly β(1)-specific β-blocker, is labeled for the treatment of hypertension in the United States. In addition to its β-blocking effects, nebivolol has been shown to increase endothelin-dependent nitric oxide, giving it a unique peripheral vasodilatory action. Nebivolol is extensively metabolized by cytochrome P-450 isoenzyme 2D6. In patients with heart failure, certain β-blockers antagonize excessive adrenergic stimulation and can slow the progression of the disease. Clinical trials have compared nebivolol at target dosages of 5 and 10 mg once daily with placebo and, in small trials, with carvedilol in the treatment of adults with chronic heart failure. Nebivolol appears to have beneficial effects in patients with heart failure, including improvements in left ventricular ejection fraction, left ventricular volumes, and exercise capacity. In addition, the Study of the Effects of Nebivolol Intervention on Outcomes and Rehospitalisation in Seniors with Heart Failure showed a reduction in morbidity and mortality after treatment with nebivolol when compared with placebo, though this effect appeared to be less than that of other β-blockers currently recommended for the treatment of heart failure. Nebivolol was well tolerated in all clinical trials, with the most frequently reported adverse events including bradycardia, hypotension, and dizziness. To date, no large clinical trials have compared nebivolol with currently recommended β-blockers in patients with heart failure. CONCLUSION. Nebivolol has beneficial effects in heart failure but cannot be considered equivalent to other currently accepted therapies.

Assessing the Value of Online Learning and Social Media in Pharmacy Education

Objective. To assess student preferences regarding online learning and technology and to evaluate student pharmacists’ social media use for educational purposes. Methods. An anonymous 36-question online survey was administered to third-year student pharmacists enrolled in the Drug Information and Clinical Literature Evaluation course. Results. Four hundred thirty-one students completed the survey, yielding a 96% response rate. The majority of students used technology for academic activities, with 90% using smart phones and 91% using laptop computers. Fifty-eight percent of students also used social networking websites to communicate with classmates. Conclusion. Pharmacy students frequently use social media and some online learning methods, which could be a valuable avenue for delivering or supplementing pharmacy curricula. The potential role of social media and online learning in pharmacy education needs to be further explored.

High-Risk Non-ST Elevation Acute Coronary Syndrome Outcomes in Patients Treated with Unfractionated Heparin Monitored Using Anti-Xa Concentrations Versus Activated Partial Thromboplastin Time

Background While the activated partial thromboplastin time (aPTT) is the most widely used assay to monitor unfractionated heparin (UFH), providing a general measure of the extent of anticoagulation, it does not reliably correlate with the blood concentration of heparin or its antithrombotic effect. While cost and availability have limited the widespread use of UFH in hospitals, monitoring UFH with heparin levels has been shown to reduce both the number of monitoring tests and the time to a therapeutic range. Objectives To compare outcomes in patients with non-ST elevation acute coronary syndrome (ACS) treated with weight-based UFH monitored with anti-Xa concentrations versus aPTT. Methods A retrospective chart review was completed in patients admitted with high-risk ACS and compared to the UFH arm of the SYNERGY trial. The primary outcome included the clinical endpoint of all-cause death or non-fatal myocardial infarction until time of hospital discharge. Safety endpoints evaluated included incidence of stroke and major bleeding. Results The primary endpoint occurred in 6.3% of patients in the study cohort compared to 6.5% of patients in the heparin arm of the SYNERGY trial at 48 hours (P = .006). Bleeding was reduced in the study cohort with a significant decrease in GUSTO severe bleeding (P = .007). Additionally the study cohort had significantly fewer patients with an absolute drop in hemoglobin or hematocrit. Thrombolysis in Myocardial Infarction (TIMI) major and minor bleeding, rate of transfusion, and platelet counts were similar between groups. Conclusions Outcomes for high-risk ACS patients receiving heparin monitored by anti-Xa concentrations are noninferior to heparin monitored by aPTT.

Invited Review: Acute Respiratory Distress Syndrome: Use of Specialized Nutrients in Pediatric Patients and Infants

With a high rate of mortality, acute respiratory distress syndrome (ARDS) has limited treatments options. Immune-enhanced formulas, containing eicosapentaenoic acid, borage oil, and antioxidants, have shown to be beneficial in adults patients with ARDS, decreasing mortality, length of mechanical ventilation, and new organ dysfunction. There is promising research in pediatric patients with improvement in oxygenation status found, but further trials are needed to realize these benefits in pediatric and infant populations.