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Purpose: To describe the perceptions of residency candidates, residency practitioners (current residents and preceptors), and residency program directors (RPDs) regarding a virtual interview process for pharmacy residency programs across multiple institutions., Methods: In May 2021, an anonymous web-based questionnaire characterizing perceptions of the virtual interview process used during the coronavirus disease 2019 (COVID-19) pandemic was distributed to residency candidates, residency practitioners, and RPDs across 13 institutions. Quantitative responses measured on a 5-point Likert scale were summarized with descriptive statistics, and open-ended questions were analyzed using thematic qualitative methods., Results: 236 residency candidates and 253 residency practitioners/RPDs completed the questionnaire, yielding response rates of 27.8% (236 of 848), and 38.1% (253 of 663), respectively. Overall, both groups perceived the virtual interview format positively. When asked whether virtual interviews should replace in-person interviews moving forward, 60.0% (18 of 30) of RPDs indicated they agreed or strongly agreed, whereas only 30.5% (61 of 200) of current preceptors/residents and 28.7% (66 of 230) of residency candidates agreed or strongly agreed. Thematic analysis of qualitative responses revealed that while virtual interviews were easier logistically, the lack of in-person interactions was a common concern for many stakeholders. Lastly, the majority (65.0%) of residency candidates reported greater than $1,000 in savings with virtual interviews., Conclusion: Virtual interviews offered logistical and financial benefits. The majority of RPDs were in favor of offering virtual interviews to replace in-person interviews, whereas the majority of residency candidates and practitioners preferred on-site interviews. As restrictions persist with the ongoing pandemic, our results provide insight into best practices for virtual pharmacy residency interviews., (© American Society of Health-System Pharmacists 2022. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Research is foundational for evidence-based management of patients. Clinical research, however, takes time to plan, conduct, and disseminate-a luxury that is rarely available during a public health emergency. The University of Nebraska Medical Center (UNMC) developed a single institutional review board (IRB), with a vision to establish a rapid review resource for a network focused on clinical research of emerging pathogens in the United States. A core aspect of successful initiation of research during a pandemic or epidemic is the ability to operationalize an approach for rapid ethical review of human subject research and conduct those reviews at multiple sites-without losing any of the substantive aspects of ethics review. This process must be cultivated in anticipation of a public health emergency. US guidance for operationalizing IRB review for multisite research in a public health emergency is not well studied and processes are not well established. UNMC sought to address operational gaps and identify the unique procedural needs of rapid response single IRB (RR-sIRB) review of multisite research by conducting a series of preparedness exercises to develop and test the RR-sIRB model. For decades, emergency responder, healthcare, and public health organizations have conducted emergency preparedness exercises to test requirements for emergency response. In this article, we describe 2 types of simulation exercises conducted by UNMC: workshops and tabletops. This effort represents a unique use of emergency preparedness exercises to develop, refine, and test rapid review functions for an sIRB and to validate readiness of regulatory research processes. Such processes are crucial for conducting rapid, ethical, and sound clinical research in public health emergencies.

Plastics have long been an environmental contaminant of concern as both large-scale plastic debris and as micro- and nano-plastics with demonstrated wide-scale ubiquity. Research in the past decade has focused on the potential toxicological risks posed by microplastics, as well as their unique fate and transport brought on by their colloidal nature. These efforts have been slowed by the lack of analytical techniques with sufficient sensitivity and selectivity to adequately detect and characterize these contaminants in environmental and biological matrices. To improve analytical analyses, microplastic tracers are developed with recognizable isotopic, metallic, or fluorescent signatures capable of being identified amidst a complex background. Here we describe the synthesis, characterization, and application of a novel synthetic copolymer nanoplastic based on polystyrene (PS) and poly(2-vinylpyridine) (P2VP) intercalated with gold, platinum or palladium nanoparticles that can be capped with different polymeric shells meant to mimic the intended microplastic. In this work, particles with PS and polymethylmethacrylate (PMMA) shells are used to examine the behavior of microplastic particles in estuarine sediment and coastal waters. The micro- and nanoplastic tracers, with sizes between 300 and 500 nm in diameter, were characterized using multiple physical, chemical, and colloidal analysis techniques. The metallic signatures of the tracers allow for quantification by both bulk and single-particle inductively-coupled plasma mass spectrometry (ICP-MS and spICP-MS, respectively). As a demonstration of environmental applicability, the tracers were equilibrated with sediment collected from Bellingham Bay, WA, United States to determine the degree to which microplastics bind and sink in an estuary based of grain size and organic carbon parameters. In these experiments, between 80 and 95% of particles were found to associate with the sediment, demonstrative of estuaries being a major anticipated sink for these contaminants. These materials show considerable promise in their versatility, potential for multiplexing, and utility in studying micro- and nano-plastic transport in real-world environments., Competing Interests: ST was employed by Postnova Analytics Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Rauschendorfer, Whitham, Summer, Patrick, Pierce, Sefi-Cyr, Tadjiki, Kraft, Emory, Rider and Montaño.)

Background: Nutrition therapy is essential in critically ill adults. Little is known about appropriate nutrition therapy in patients with severe coronavirus disease 2019 (COVID-19) infection., Methods: This was a retrospective, observational study in adult patients with confirmed COVID-19 infection receiving mechanical ventilation. Data regarding patient demographics and nutrition therapy were collected. Patients that received enteral nutrition within 24 hours of starting mechanical ventilation were compared with patients starting enteral nutrition later. The primary outcome was inpatient length of stay. Propensity score matching was conducted to control for baseline differences in patient groups., Results: One hundred fifty-five patients were included in final analysis. Patients who received enteral nutrition within 24 hours received a significantly greater daily amount of calories (17.5 vs 15.2 kcal/kg, P = .015) and protein (1.04 vs 0.85 g/kg, P = .003). There was no difference in length of stay (18.5 vs 23.5 days, P = .37). The propensity score analysis included 100 patients. Following propensity scoring, significant differences in daily calorie (17.7 [4.6] vs 15.1 [5.1] kcal/kg/d, P = .009) and protein (1.03 [0.35] vs 0.86 [0.38] g/kg/d, P = .014) provision remained. No differences in length of stay or other outcomes were noted in the propensity score analysis., Conclusion: Initiation of enteral nutrition within 24 hours was not associated with improved outcomes in mechanically ventilated adults with COVID-19. No harm was detected either. Future research should seek to clarify optimal timing of enteral nutrition initiation in patients with COVID-19 who require mechanical ventilation., (© 2021 American Society for Parenteral and Enteral Nutrition.)

Parenteral nutrition (PN) is a complex therapy with numerous opportunities for error during the prescribing, preparation, and administration processes. Advances in technology, such as computerized provider order entry (CPOE), electronic health records (EHRs), and clinical decision support (CDS) have helped decrease the risks associated with PN therapy. These technologies can be utilized to guide prescribing, provide automated safety checks, and increase overall safety and accuracy in PN ordering, compounding, and administration. In recent years, increased awareness of the risks associated with PN therapy, in particular issues with ordering and transcription, have magnified the need for improved support of PN ordering within currently available systems. Additionally, drug shortages continue to impact key components of PN admixtures, further increasing the risks associated with this complex therapy. These concerns and risks present an opportunity for the development of new functionality, as well as improvements in and innovative utilization of available technology within systems supporting the PN use process. This discussion will highlight the risks associated with PN, examine the role of drug shortages on the safety of this therapy, describe the application of available technology to manage shortages, and report the experience of using commercially available CDS tools at one academic medical center. It will also include a discussion of the transition from paper orders to CPOE/EHR-based orders for PN and the transition from one commercially available electronic system to another at this particular institution., (© 2020 American Society for Parenteral and Enteral Nutrition.)

Introduction: Errors have been reported in the literature to occur at each step of the parenteral nutrition (PN) use process, necessitating standardized processes, clinician competence, and open communication for those involved. This study was performed at Central Admixture Pharmacy Services (CAPS®) in collaboration with the American Society for Parenteral and Enteral Nutrition (ASPEN) with the purpose to study the need for and success of PN pharmacist interventions., Methods: A survey was developed and sent to all CAPS customers for study enrollment and to identify their demographic and practice characteristics. For those enrolled, CAPS pharmacists reviewed every PN order in a 1-month period using an error/intervention tool to capture data on prescription elements requiring intervention, along with acceptance of that intervention., Results: Two hundred thirty-two unique CAPS customers (23% response rate) participated in the study, representing 37,634 unique PN prescriptions. Two hundred forty-eight PN prescriptions (0.66%) from 59 customers required ≥1 intervention. The top 3 intervention types were electrolyte dose clarification, calcium/phosphorus incompatibility, and amino acid dose clarification. A greater number and percentage of interventions were required for neonatal prescriptions, as compared with adult and pediatric prescriptions. No significant difference was found in many of the other customer characteristics., Conclusion: This study supports the need for institutions to develop systems to comply with published PN safety recommendations, including knowledgeable and skilled pharmacists to complete the order review and verification steps for this high-alert medication., (© 2020 American Society for Parenteral and Enteral Nutrition.)

Intravenous in-line filters play a critical role in promoting patient safety during parenteral nutrition (PN) administration. Guidelines for using filters for PN have been issued by a number of professional organizations and manufacturers of PN components. Yet despite this guidance, filter use remains controversial. Recent changes in recommendations for filtering lipid injectable emulsions have added to confusion and created considerable variation in practice. This Position Paper aims to review past guidance regarding the filtration of PN, examine the clinical consequences of infusing particulate matter, discuss the challenges and issues related to filtration, and clarify the American Society for Parenteral and Enteral Nutrition (ASPEN) recommendations for the use of filters for PN administration. This paper was approved by the ASPEN Board of Directors., (© 2020 American Society for Parenteral and Enteral Nutrition.)

The 2013-2016 epidemic of Ebola virus disease (EVD) that originated in West Africa underscored many of the challenges to conducting clinical research during an ongoing infectious disease epidemic, both in the most affected countries of Guinea, Liberia, and Sierra Leone, as well as in the United States and Europe, where a total of 27 patients with EVD received care in biocontainment units. The Special Pathogens Research Network (SPRN) was established in the United States in November 2016 to provide an organizational structure to leverage the expertise of the 10 Regional Ebola and Other Special Pathogen Treatment Centers (RESPTCs); it was intended to develop and support infrastructure to improve readiness to conduct clinical research in the United States. The network enables the rapid activation and coordination of clinical research in the event of an epidemic and facilitates opportunities for multicenter research when the RESPTCs are actively caring for patients requiring a biocontainment unit. Here we provide an overview of opportunities identified in the clinical research infrastructure during the West Africa EVD epidemic and the SPRN activities to meet the ongoing challenges in the context of Ebola virus and other special pathogens.

The use of investigational therapeutics in the care of patients with Ebola virus disease was documented in the literature following the 2013-2016 outbreak. In order to access these types of therapeutics, facilities must have processes in place to quickly and efficiently activate study protocols, obtain the medications, and administer them in a timely manner. Testing these procedures in advance of a real-world event is crucial to ensuring successful implementation and execution. Drills and exercises are routinely used as part of the emergency preparedness planning process, as they provide a low-risk environment in which to test plans and procedures. Including research activities in full-scale emergency preparedness exercises is a novel approach that should be considered when creating a comprehensive special pathogen program. One important aspect of creating an agile response program is developing and sustaining strong relationships with key collaborators. Including departments not previously engaged in infectious disease preparedness exercises provides a forum to strengthen these relationships, clarify roles, and identify gaps. This article describes the process used to incorporate research-centric objectives focused on the use of investigational therapeutics for Ebola virus disease into a full-scale exercise, the evaluation process used to measure the identified objectives, and the results of the exercise.

The National Ebola Training and Education Center (NETEC) was established in 2015 in response to the 2014-2016 Ebola virus disease outbreak in West Africa. The US Department of Health and Human Services office of the Assistant Secretary for Preparedness and Response and the US Centers for Disease Control and Prevention sought to increase the competency of healthcare and public health workers, as well as the capability of healthcare facilities in the United States, to deliver safe, efficient, and effective care to patients infected with Ebola and other special pathogens nationwide. NYC Health + Hospitals/Bellevue, Emory University, and the University of Nebraska Medical Center/Nebraska Medicine were awarded this cooperative agreement, based in part on their experience in safely and successfully evaluating and treating patients with Ebola virus disease in the United States. In 2016, NETEC received a supplemental award to expand on 3 initial primary tasks: (1) develop metrics and conduct peer review assessments; (2) develop and provide educational materials, resources, and tools, including exercise design templates; (3) provide expert training and technical assistance; and, to add a fourth task, create a special pathogens clinical research network.

Background: Shortages of parenteral nutrition (PN) components have been common in recent years. Effects on patient management and outcomes have not been well documented. This study aimed to determine the effect of a parenteral magnesium shortage, and an institutional decision to omit magnesium from adult PN, on magnesium and potassium doses and serum concentrations., Materials and Methods: This was a retrospective cohort study of adult surgical patients during two 6-month periods: prior to the magnesium shortage (2011) and during the shortage (2012). The relation between study period and electrolyte doses was evaluated by unadjusted and adjusted mixed models, while the relation between study period and hypokalemia and hypomagnesemia exposure was evaluated by Student's t tests and multiple linear regression., Results: During the shortage, patients received more supplemental magnesium (0.11-0.12 mEq/kg/d, P < .0001) but received less total daily magnesium (0.08-0.09 mEq/kg/d, P < .0001) and had greater exposure to hypomagnesemia (9.6-14.2 h·mcg/dL/h, P < .05 for all comparisons except multivariate analysis in a matched subpopulation). Patients received similar amounts of potassium in PN (0.06-0.08 mEq/kg/d less, P < .05 for full cohort but P > .05 for matched cohort), in supplemental doses (0.01-0.05 mEq/kg/d less, P > .05), and in total (0.07-0.14 mEq/kg/d less, P > .05), and they had similar exposure to hypokalemia., Conclusion: Daily magnesium doses were lower and hypomagnesemia exposure was greater during the shortage, but the differences were numerically small and their clinical significance was questionable. Potassium doses and hypokalemia exposure were not higher during the shortage. This supports the strategy of omitting magnesium from PN of select patients and supplementing as clinically necessary., (© 2015 American Society for Parenteral and Enteral Nutrition.)

Purpose: To assist the pharmacy clinician engaged in nutrition support in staying current with the most pertinent literature., Methods: Several experienced board-certified clinical pharmacists engaged in nutrition support therapy compiled a list of articles published in 2014 and 2015 that they considered to be important to their practice. Only those articles available in print format were considered for potential inclusion. Articles available only in preprint electronic format were not evaluated. The citation list was compiled into a single spreadsheet where the author participants were asked to ascertain whether they considered the paper important to nutrition support pharmacy practice. A culled list of publications was then identified whereby the majority of author participants (at least 5 out of 8) considered the paper to be important., Results: A total of 108 articles were identified; 36 of which were considered to be of high importance. An important guideline article published in early 2016, but not ranked, was also included. The top-ranked articles from the primary literature were reviewed., Conclusion: It is recommended that the informed pharmacist, who is engaged in nutrition support therapy, be familiar with the majority of these articles.

Objective: Comorbidities such as cardiovascular diseases (CVD), cancer, osteoporosis, and depression are often underrecognized in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or psoriasis (PsO). Recommendations may improve identification and treatment of comorbidities. The Canadian Dermatology-Rheumatology Comorbidity Initiative reviewed the literature to develop practical evidence-based recommendations for management of comorbidities in patients with RA, PsA, and PsO., Methods: Eight main topics regarding comorbidities in RA, PsA, and PsO were developed. MEDLINE, EMBASE, and the Cochrane Library (1960-12/2012), together with abstracts from major rheumatology and dermatology congresses (2010-2012), were searched for relevant publications. Selected articles were analyzed and metaanalyses performed whenever possible. A meeting including rheumatologists, dermatologists, trainees/fellows, and invited experts was held to develop consensus-based recommendations using a Delphi process with prespecified cutoff agreement. Level of agreement was measured using a 10-point Likert scale (1 = no agreement, 10 = full agreement) and the potential effect of recommendations on daily clinical practice was considered. Grade of recommendation (ranging from A to D) was determined according to the Oxford Centre for Evidence-Based Medicine evidence levels., Results: A total of 17,575 articles were identified, of which 407 were reviewed. Recommendations were synthesized into 19 final recommendations ranging mainly from grade C to D, and relating to a large spectrum of comorbidities observed in clinical practice: CVD, obesity, osteoporosis, depression, infections, and cancer. Level of agreement ranged from 80.9% to 95.8%., Conclusion: These practical evidence-based recommendations can guide management of comorbidities in patients with RA, PsA, and PsO and optimize outcomes.

Phosphorus (P) and calcium (Ca) serve vital roles in the human body and are essential components of nutrition support therapy. Regulation of P and regulation of Ca in the body are closely interrelated, and P and Ca homeostasis can be affected by several factors, including disease states, clinical condition, severity of illness, and medications. Nutrition support clinicians must understand these factors to prevent and treat P and Ca disorders in patients receiving nutrition support therapy. This review provides an overview of P and Ca for the adult nutrition support clinician, with some emphasis on the hospitalized inpatient., (© 2014 American Society for Parenteral and Enteral Nutrition.)

Purpose: To assist the pharmacy clinician engaged in nutrition support in staying current with the most pertinent literature., Methods: Several experienced board-certified clinical pharmacists in nutrition support compiled a list of publications published in 2013 that they considered to be important to their practice. The citation list was compiled into a Web-based survey whereby pharmacist members of the American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.), GI-Liver-Nutrition Practice Research Network of the American College of Clinical Pharmacy, and the Pharmacy and Pharmacology Section of the Society of Critical Care Medicine were asked to rank each article according to level of importance in their practice., Results: A total of 30 articles were identified by the author group. Thirty-six participants responded to the survey. The top-ranked papers by participants from the Web-based survey were reviewed by the authors. Due to its high level of importance, the parenteral nutrition safety consensus recommendations article, to be published in 2014 by A.S.P.E.N., was also reviewed., Conclusion: It is recommended that the informed pharmacist, who is engaged in nutrition support therapy, be familiar with the majority of these publications.

Objective: Venous thromboembolism (VTE) is the leading cause of preventable death in hospitalized patients. Educational videos have been effectively used to increase patient satisfaction and knowledge. This study examined possible benefits of an educational video about VTE., Methods: Medical patients receiving VTE prophylaxis were screened within 48 h of admission. Upon enrollment, patients were randomly assigned to either watch a 5 min educational video on VTE or not, in addition to standard VTE education. Within 24-48 h after randomization, all patients completed a survey assessing VTE prophylaxis knowledge and satisfaction., Results: Patients who watched the video averaged 83% correct responses to knowledge-based questions (regarding VTE risk, symptoms, and preventative measures) versus an average score of 62% for patients in the no video group (p<0.001). Patients who watched the video were more satisfied with their VTE education (4.8 vs. 3.4 out of 5, p<0.001)., Conclusion: This educational video effectively provided baseline information to patients about VTE and improved patient satisfaction., Practice Implications: A VTE educational video can be an effective tool for improving patient knowledge of the condition., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Alkalinized Viokase pancreatic enzyme tablets restored patency to 71.9% of occluded Dobhoff tubes in a prospective study. After removal of Viokase tablets from the US market, the hospital protocol for unclogging enteral feeding tubes was adapted to use Creon pancreatic enzyme delayed-release capsules, despite the lack of published data., Objective: To evaluate the effectiveness of a Creon-based protocol to clear occluded enteral feeding tubes., Methods: This retrospective study included all adult and pediatric patients seen in the emergency department or in an inpatient setting who received Creon 12 000 units lipase delayed-release capsule dissolved in a solution of sodium bicarbonate 650 mg and sterile water for clearing occluded enteral feeding tubes between May 1 and November 30, 2010. The Creon protocol was deemed effective if tube clearance was documented in the medical record or if enteral feedings were resumed with no note regarding tube replacement., Results: Alkalinized Creon delayed-release capsules were administered to 83 patients with a total of 118 clogged tubes. Three poorly documented cases and 5 tubes with mechanical clogs were excluded from data analysis. Patency was restored to 53 of 110 (48.2%) occluded tubes. More than 1 treatment course was attempted in 5 cases, with success in 3., Conclusion: An alkalinized Creon pancreatic enzyme protocol was effective in clearing approximately half of the occluded enteral feeding tubes in this retrospective study, an efficacy rate much less than that previously reported in the literature with a Viokase-based protocol.

Parenteral nutrition (PN) serves as an important therapeutic modality that is used in adults, children, and infants for a variety of indications. The appropriate use of this complex therapy aims to maximize clinical benefit while minimizing the potential risks for adverse events. Complications can occur as a result of the therapy and as the result of the PN process. These consensus recommendations are based on practices that are generally accepted to minimize errors with PN therapy, categorized in the areas of PN prescribing, order review and verification, compounding, and administration. These recommendations should be used in conjunction with other A.S.P.E.N. publications, and researchers should consider studying the questions brought forth in this document.

Background: Vasopressors used for the management of septic shock are often dosed according to body weight. Use of vasopressin for physiologic replacement in patients with septic shock is usually administered as a standard non-weight-based dose. We hypothesized that the efficacy of vasopressin may be influenced by body weight., Purpose: The primary objective was to determine if the effects of vasopressin on other vasopressor dosing requirements is related to body weight. Secondary objectives included evaluation of blood pressure and heart rate after the start of vasopressin infusion., Methods: A retrospective, cohort study in a large academic health center was conducted. Sixty-four adult inpatients with septic shock (26 medical intensive care unit and 38 surgical intensive care unit) who required vasopressor administration including vasopressin therapy were included. Dosing requirements of vasopressors were captured 1 hour before and during the hour of vasopressin initiation and 2 and 4 hours later. Other information collected during the study period included blood pressure, mean arterial pressure, and heart rate., Results: Most of the patients (n = 61) received vasopressin at a dose of 0.04 U/min. Changes in vasopressor dosing were significantly correlated with weight-adjusted vasopressin at 2 hours (correlation coefficient = -0.36, P = .03) and 4 hours (correlation coefficient = -0.46, P < .001). Use of vasopressin was associated with significant increases in systolic blood pressure, diastolic blood pressure, and mean arterial pressure at each time point compared with baseline., Conclusions: Effects of vasopressin on catecholamine dosing requirements in the setting of septic shock may be influenced by body weight. Prospective studies are needed to examine weight-based dosing of vasopressin in this setting., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Critically ill patients who are subjected to high stress or with severe injury can rapidly break down their body protein and energy stores. Unless adequate nutrition is provided, malnutrition and protein wasting may occur, which can negatively affect patient outcome. Enteral nutrition (EN) is the mainstay of nutrition support therapy in patients with a functional gastrointestinal (GI) tract who cannot take adequate oral nutrition. EN in critically ill patients provides the benefits of maintaining gut functionality, integrity, and immunity as well as decreasing infectious complications. However, the ability to provide timely and adequate EN to critically ill patients is often hindered by GI motility disorders and complications associated with EN. This paper reviews the GI complications and intolerances associated with EN in critically ill patients and provides recommendations for their prevention and treatment. It also addresses the role of commonly used medications in the intensive care unit and their impact on GI motility and EN delivery.

Purpose: The economic effect of the use of alvimopan in four randomized, double-blind, placebo-controlled, Phase III, North American efficacy trials was analyzed., Methods: Patients were eligible for the study if they were 18 years or older, were undergoing laparotomy for partial small or large bowel resection with primary anastomosis, and were scheduled for postoperative pain management with opioid-based i.v. patient-controlled analgesia. Patients analyzed in the North American Phase III trials received placebo or alvimopan 12 mg orally before surgery. Doses were administered twice daily beginning the day after surgery until hospital discharge or for a maximum of 15 doses., Results: Compared with placebo, alvimopan was associated with a significantly shorter mean time to gastrointestinal (GI) recovery and a significantly shorter mean time to a written discharge order. Alvimopan was also associated with a mean hospital length of stay (LOS) of one full day less than placebo. The mean cost of alvimopan based on a mean of 8.9 12-mg doses was $558.00; the alvimopan cost at the upper limit of allowed dosing was $937.50. Combining the alvimopan and hospital costs for each patient, total costs for the alvimopan group were estimated to be lower than for the placebo group., Conclusion: In a post hoc analysis, alvimopan was associated with significantly faster upper and lower GI recovery after bowel resection and a mean LOS reduction of one day compared with placebo. The mean estimated hospital cost was $879-$977 less for patients who received alvimopan compared with placebo. The base-case and sensitivity analyses suggest that, on average, the use of alvimopan compared with placebo may have a cost-saving effect in the hospital setting.

Postoperative ileus (POI), a transient impairment of bowel function, is considered an inevitable response after open abdominal surgery. It leads to significant patient morbidity and increased hospital costs and length of stay. The pathophysiology is multifactorial, involving neurogenic, hormonal, inflammatory and pharmacologic mediators. Several treatments have been shown to reduce the duration of POI, and a multimodal approach combining several of these interventions seems to be the most effective treatment option. Various drug therapies have been evaluated for the treatment of POI, although most have not shown any benefit. Peripherally active mu-opioid receptor antagonists are a new class of compounds that selectively block the peripheral (i.e., gastrointestinal [GI]) effects of opioids while preserving centrally mediated analgesia. Recently, alvimopan was approved in the US for the treatment of POI after abdominal surgery with bowel resection. Methylnaltrexone is a peripherally active mu-opioid receptor antagonist that has been shown to antagonize the inhibitory effects of opioids on GI transit without impairing analgesia. Phase II data indicated that methylnaltrexone was effective for improving GI recovery, reducing POI and shortening the time to discharge readiness in patients who underwent segmental colectomy. Two Phase III trials have been completed, and one is underway at present. Preliminary results from the two completed trials indicate that methylnaltrexone was not better than placebo for the primary or secondary outcomes. Further analyses of these data, clinical trial designs and the various dosage forms are necessary to determine the potential role of methylnaltrexone in the treatment of POI.

Purpose: The stability of metoprolol tartrate injection 1 mg/mL undiluted and 0.5 mg/mL in 0.9% sodium chloride injection and 5% dextrose injection was studied., Methods: Sample set A contained 50 mL of Metoprolol Tartrate Injection, USP, 1 mg/mL transferred directly from the vials. Sample set B contained 50 mL of metoprolol 0.5 mg/mL diluted with 0.9% sodium chloride injection, and sample set C contained 50 mL of metoprolol 0.5 mg/mL diluted with 5% dextrose. All samples were prepared in triplicate and stored at room temperature. The stability of the samples was analyzed in duplicate using stability-indicating high-performance liquid chromatography immediately after preparation and at 6, 12, 18, 24, and 30 hours. The samples were assessed for pH and inspected for color and visible precipitation changes. The stability of metoprolol was determined by evaluating the percentage of the initial concentration remaining at each time interval. Stability of the product was defined as retention of 90% of the initial concentration., Results: The mean +/- S.D. initial concentration in sample sets A, B, and C was 1.006 +/- 0.009 mg/mL, 0.498 +/- 0.002 mg/mL, and 0.499 +/- 0.002 mg/mL, respectively. Throughout the 30-hour study period, at least 99% of the initial concentration of metoprolol tartrate remained in all three preparations at all time points. No appreciable changes in pH occurred. No changes in color and no visible precipitate or microbial growth were detected., Conclusion: Metoprolol tartrate injection 1 mg/mL undiluted and 0.5 mg/mL in 0.9% sodium chloride injection and 5% dextrose injection were stable at room temperature for at least 30 hours.

Purpose: Characteristics of the ideal drug therapy for postoperative ileus (POI); the pharmacology, efficacy, and safety of currently available nonselective opioid antagonists and the new peripherally selective opioid antagonists methylnaltrexone and alvimopan for the treatment of POI; and formulary considerations associated with the introduction of these new POI drug therapies are discussed., Summary: The ideal drug therapy for treating POI would selectively antagonize the inhibitory effects on the gastrointestinal (GI) tract of all of the potential factors implicated in the pathophysiology of POI (neurogenic, inflammatory, hormonal, and pharmacologic mediators). The most promising target to date is inhibition of the adverse GI effects of endogenous and exogenous opioids. Selective inhibition of the mu-opioid receptors in the GI tract, without reversing centrally mediated opioid-induced analgesia, may be beneficial in reducing POI. The nonselective opioid antagonists naloxone and nalmefene have not been studied for POI, and they cross the blood-brain barrier. Therefore, they are not appropriate for preventing or treating POI. The peripherally selective opioid antagonist methylnaltrexone shortens the duration of POI and the hospital length of stay (LOS). Alvimopan, a more extensively studied peripherally selective opioid antagonist, has been shown to reduce the duration of POI, frequency of postoperative nausea and vomiting, and hospital LOS. Both methylnaltrexone and alvimopan also appear effective for treating opioid-induced constipation. Preliminary results of a long-term study of alvimopan safety have revealed some potential concerns, and the significance of the adverse effects must be understood before the most appropriate role of alvimopan in patient care can be determined. Restricting the prescribing of new POI drug therapies to certain types of patients, surgeries, and prescribers; incorporating these therapies into preoperative and postoperative policies, procedures, and protocols; and the potential cost savings from reducing hospital LOS are among the considerations in adding these agents to health-system formularies., Conclusion: Peripherally selective opioid receptor antagonists are promising new drug therapies that can reduce the clinical and economic burden of POI.

Refeeding syndrome describes a constellation of metabolic disturbances that occur as a result of reinstitution of nutrition to patients who are starved or severely malnourished. Patients can develop fluid and electrolyte disorders, especially hypophosphatemia, along with neurologic, pulmonary, cardiac, neuromuscular, and hematologic complications. We reviewed literature on refeeding syndrome and the associated electrolyte abnormalities, fluid disturbances, and associated complications. In addition to assessing scientific literature, we also considered clinical experience and judgment in developing recommendations for prevention and treatment of refeeding syndrome. The most important steps are to identify patients at risk for developing refeeding syndrome, institute nutrition support cautiously, and correct and supplement electrolyte and vitamin deficiencies to avoid refeeding syndrome. We provide suggestions for the prevention of refeeding syndrome and suggestions for treatment of electrolyte disturbances and complications in patients who develop refeeding syndrome, according to evidence in the literature, the pathophysiology of refeeding syndrome, and clinical experience and judgment.

Purpose: The treatment of electrolyte disorders in adult patients in the intensive care unit (ICU), including guidelines for correcting specific electrolyte disorders, is reviewed., Summary: Electrolytes are involved in many metabolic and homeostatic functions. Electrolyte disorders are common in adult patients in the ICU and have been associated with increased morbidity and mortality, as has the improper treatment of electrolyte disorders. A limited number of prospective, randomized, controlled studies have been conducted evaluating the optimal treatment of electrolyte disorders. Recommendations for treatment of electrolyte disorders in adult patients in the ICU are provided based on these studies, as well as case reports, expert opinion, and clinical experience. The etiologies of and treatments for hyponatremia hypotonic and hypernatremia (hypovolemic, isovolemic, and hypervolemic), hypokalemia and hyperkalemia, hypophosphatemia and hyperphosphatemia, hypocalcemia and hypercalcemia, and hypomagnesemia and hypermagnesemia are discussed, and equations for determining the proper dosages for adult patients in the ICU are provided. Treatment is often empirical, based on published literature, expert recommendations, and the patient's response to the initial treatment. Actual electrolyte correction requires individual adjustment based on the patient's clinical condition and response to therapy. Clinicians should be knowledgeable about electrolyte homeostasis and the underlying pathophysiology of electrolyte disorders in order to provide the optimal therapy to patients., Conclusion: Treatment of electrolyte disorders is often empirical, based on published literature, expert opinion and recommendations, and patient's response to the initial treatment. Clinicians should be knowledgeable about electrolyte homeostasis and the underlying pathophysiology of electrolyte disorders to provide optimal therapy for patients.

Objective: To determine the linezolid clearance and serum concentrations in a critically ill man receiving continuous venovenous hemodiafiltration (CVVHDF)., Methods: Intravenous linezolid 600 mg every 12 hours was administered to a critically ill, 85-year-old man with anuria who was receiving CVVHDF at a dialysate flow rate of 2000 ml/hour and a mean ultrafiltrate production rate of 775 ml/hour. Samples of blood and spent dialysate and ultrafiltrate were obtained at the time of linezolid peaks and troughs, and linezolid concentrations were determined., Results: The CVVHDF yielded a mean linezolid clearance of 36.5 ml/minute and an elimination half-life of 7.5 hours. The linezolid saturation coefficient ranged from 0.77-0.81. Administration of intravenous linezolid 600 mg every 12 hours yielded suitable serum trough concentrations., Conclusion: Administration of intravenous linezolid 600 mg every 12 hours maintained therapeutic serum trough concentrations in this critically ill patient receiving CVVHDF.

N-Nitrosodimethylamine is a liver toxin and mutagen following activation by cytochrome P450. The role of the cytosol in N-nitrosodimethylamine metabolism is not well understood. The effect of cytosol on N-nitrosodimethylamine metabolism was investigated using microsomes and cytosol from rat liver in in vitro reactions with N-nitrosodimethylamine and an NADPH generating system. Studies in which [(14)C]-N-nitrosodimethylamine and calf thymus DNA were used indicated that the addition of cytosol to the microsomal reaction mixture resulted in >200% enhancement of the radioactivity associated with DNA after the DNA was isolated from the reaction mixture by phenol extraction followed by ethanol precipitation. This stimulatory effect was associated with a cytosolic protein and was found to be dependent on both the microsomes and the carbohydrate used in the glucose-6-phosphate dehydrogenase system for the generation of NADPH. The carbohydrate requirement was found to be specific for intermediates of the pentose phosphate pathway, and maximum stimulation occurred with ribulose 5-phosphate. Most of the counts from [(14)C]-N-nitrosodimethylamine which were isolated with DNA after the addition of cytosol to reaction mixtures were not covalently bound to the DNA. HPLC analysis identified four radiolabeled metabolites derived from [(14)C]-N-nitrosodimethylamine following the in vitro incubations. One of the four products was formed only when both cytosol and ribulose 5-phosphate were added to the enzymatic incubations. This product also formed from [(14)C]-alpha-acetoxy nitrosodimethylamine in the absence of microsomes, only when cytosol and ribulose 5-phosphate were added to the reaction mixtures. Thus, these data demonstrate that an enzyme in the cytosol catalyzes a reaction involving a metabolite of N-nitrosodimethylamine (which is formed following cytochrome P450-mediated activation) and a carbohydrate related to the pentose phosphate pathway. A similar reaction also occurs with N-diethylnitrosamine but not with N-dipropylnitrosamine or N-dibutylnitrosamine.