Significant Published Articles in 2021 for Pharmacy Nutrition Support Practice.

Purpose: The purpose of this article is to assist the pharmacist engaged in nutrition support therapy in staying current with pertinent literature. Methods: Several clinical pharmacists engaged in nutrition support therapy compiled a list of articles published in 2021 considered important to their clinical practice. The citation list was compiled into a single spreadsheet where the author participants were asked to assess whether the article was considered important to nutrition support pharmacy practice. A culled list of publications was then identified whereby at least 5 out of the 8 author participants considered the paper to be important. Guideline and consensus papers from professional organizations, important to practice but not ranked, were also included. Results: A total of 211 articles were identified; 8 from the primary literature were voted by the group to be of high importance. An additional 18 guidelines, position, recommendation, or consensus papers were also identified. The top-ranked articles from the primary literature were summarized and a narrative regarding its implications to pharmacy nutrition support practice were provided. Conclusion: We recommend that pharmacists engaged in nutrition support therapy be familiar with these articles as it pertains to their practice.

Significant Published Articles in 2020 for Pharmacy Nutrition Support Practice.

Purpose: The purpose of this article is to assist the pharmacist engaged in nutrition support therapy in staying current with pertinent literature. Methods: Several clinical pharmacists engaged in nutrition support therapy compiled a list of articles published in 2020 considered important to their clinical practice. The citation list was compiled into a single spreadsheet where the author participants were asked to assess whether the article was considered important to nutrition support pharmacy practice. A culled list of publications was then identified whereby at least 5 out of the 8 author participants considered the paper to be important. Guideline and consensus papers from professional organizations, important to practice but not ranked, were also included. Results: A total of 169 articles were identified; 5 from the primary literature were voted by the group to be of high importance. An additional 17 guidelines, position, recommendation, or consensus papers were also identified. The top-ranked articles from the primary literature were summarized and a narrative regarding its implications to pharmacy nutrition support practice were provided. Conclusion: We recommend that pharmacists engaged in nutrition support therapy be familiar with these articles as it pertains to their practice.

PBPK modeling of CYP3A and P-gp substrates to predict drug-drug interactions in patients undergoing Roux-en-Y gastric bypass surgery.

Roux-en-Y gastric bypass surgery (RYGBS) is an effective surgical intervention to reduce mortality in morbidly obese patients. Following RYGBS, the disposition of drugs may be affected by anatomical alterations and changes in intestinal and hepatic drug metabolizing enzyme activity. The aim of this study was to better understand the drug-drug interaction (DDI) potential of CYP3A and P-gp inhibitors. The impacts of RYGBS on the absorption and metabolism of midazolam, acetaminophen, digoxin, and their major metabolites were simulated using physiologically-based pharmacokinetic (PBPK) modeling. PBPK models for verapamil and posaconazole were built to evaluate CYP3A- and P-gp-mediated DDIs pre- and post-RYGBS. The simulations suggest that for highly soluble drugs, such as verapamil, the predicted bioavailability was comparable pre- and post-RYGBS. For verapamil inhibition, RYGBS did not affect the fold-change of the predicted inhibited-to-control plasma AUC ratio or predicted inhibited-to-control peak plasma concentration ratio for either midazolam or digoxin. In contrast, the predicted bioavailability of posaconazole, a poorly soluble drug, decreased from 12% pre-RYGBS to 5% post-RYGBS. Compared to control, the predicted posaconazole-inhibited midazolam plasma AUC increased by 2.0-fold pre-RYGBS, but only increased by 1.6-fold post-RYGBS. A similar trend was predicted for pre- and post-RYGBS inhibited-to-control midazolam peak plasma concentration ratios (2.0- and 1.6-fold, respectively) following posaconazole inhibition. Absorption of highly soluble drugs was more rapid post-RYGBS, resulting in higher predicted midazolam peak plasma concentrations, which was further increased following inhibition by verapamil or posaconazole. To reduce the risk of a drug-drug interaction in patients post-RYGBS, the dose or frequency of object drugs may need to be decreased when administered with highly soluble inhibitor drugs, especially if toxicities are associated with plasma peak concentrations.

Energy Expenditure and Shivering Severity During Targeted Temperature Management at 36°C After Cardiac Arrest: A Case Series.

Patients undergoing targeted temperature management (TTM) after cardiac arrest are at risk for shivering, which increases energy expenditure (EE) and may attenuate TTM benefits. This article reports patterns of EE for patients with and without shivering who received TTM at 36°C after cardiac arrest. Based on 96 case assessments, there were 14 occasions when more than one 15-minute interval period was required to appropriately modify the Bedside Shivering Assessment Scale (BSAS) score. Investigators noted that although higher EE was related to higher BSAS scores, there may be opportunities for earlier detection of shivering.

Significant Published Articles for Pharmacy Nutrition Support Practice in 2018.

Purpose: The purpose of this article is to assist the pharmacist engaged in nutrition support therapy in staying current with pertinent literature. Methods: Several clinical pharmacists engaged in nutrition support therapy compiled a list of articles published in 2018 considered important to their clinical practice. The citation list was compiled into a single spreadsheet where the author participants were asked to assess whether the article was considered important to nutrition support pharmacy practice. A culled list of publications was then identified whereby the majority of author participants (at least 5 of 8) considered the paper to be important. Guideline and consensus papers from professional organizations, important to practice but not scored, were also included. Results: A total of 117 articles were identified; 8 from the primary literature were voted by the group to be of high importance. An additional 13 organizational guidelines, position, recommendation, or consensus papers were also identified. The top-ranked articles from the primary literature were reviewed. Conclusion: We recommend that pharmacists engaged in nutrition support therapy be familiar with these articles as it pertains to their practice.

Significant Published Articles for Pharmacy Nutrition Support Practice in 2017.

Purpose: The purpose of the article is to assist the pharmacist engaged in nutrition support therapy in staying current with pertinent literature. Methods: Several clinical pharmacists engaged in nutrition support therapy compiled a list of articles published in 2017 considered important to their clinical practice. The citation list was compiled into a spreadsheet where the author participants were asked to assess whether the article was considered important to nutrition support pharmacy practice. A culled list of publications was then identified whereby the majority (at least 5 out of 8 authors) considered the article to be of significance. Guideline and consensus articles from professional organizations, important to practice but not scored, were also included. Results: A total of 95 articles were identified; six from the primary literature were voted by the group to be of high importance. An additional 13 organizational guidelines, position, recommendation, or consensus papers were also identified. The top-ranked articles from the primary literature were reviewed. Conclusion: It is recommended that pharmacists engaged in nutrition support therapy be familiar with these articles as it pertains to their practice.

Significant Published Articles for Pharmacy Nutrition Support Practice in 2016.

Purpose: To assist the pharmacist engaged in nutrition support therapy in staying current with pertinent literature. Methods: Several clinical pharmacists engaged in nutrition support therapy compiled a list of articles published in 2016 considered important to their clinical practice. The citation list was compiled into a single spreadsheet where the author participants were asked to assess whether the paper was considered 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. Guideline and consensus papers from professional organizations, important to practice but not scored, were also included. Results: A total of 103 articles were identified; 10 from the primary literature were voted by the group to be of high importance. An additional 11 organizational guidelines, position, recommendation, or consensus papers were also identified. The top-ranked articles from the primary literature were reviewed. Conclusion: It is recommended that pharmacists, engaged in nutrition support therapy, be familiar with the majority of these articles as it pertains to their practice.

Pharmacokinetics of the etonogestrel contraceptive implant in obese women.

OBJECTIVE: We sought to examine the pharmacokinetics and acceptability of the etonogestrel contraceptive implant in obese women. STUDY DESIGN: We developed and validated a plasma etonogestrel concentration assay and enrolled 13 obese (body mass index ≥30) women and 4 normal-weight (body mass index <25) women, who ensured comparability with historical controls. Etonogestrel concentrations were measured at 50-hour intervals through 300 hours postinsertion, then at 3 and 6 months to establish a pharmacokinetic curve. RESULTS: All obese participants were African American, while all normal-weight participants were white. Across time, the plasma etonogestrel concentrations in obese women were lower than published values for normal-weight women and 31-63% lower than in the normal-weight study cohort, although these differences were not statistically significant. The implant device was found highly acceptable among obese women. CONCLUSION: Obese women have lower plasma etonogestrel concentration than normal-weight women in the first 6 months after implant insertion. These findings should not be interpreted as decreased contraceptive effectiveness without additional considerations.

Forty-Fourth ASPEN Presidential Address: The 2020 Overture-A New Tune for the Future.

The provision of safe nutrition care to patients is the fundamental vision of the American Society for Parenteral and Enteral Nutrition (ASPEN). Yet we are facing important challenges in our field and society, requiring us to reflect, rethink, and adjust to make new breakthroughs to meet the needs for the future. In developing new plans to address these challenges, we must focus on 2 critical elements: people and the scientific process. Government and organizations cannot carry on their missions without people. But with the challenges of healthcare finance, biotechnology disruption, the desire to facilitate knowledge transfer and now the impact of the global pandemic, we need to develop a forward-thinking and sustainable approach to connect people and foster continued learning. Burnout is a recognized occupational problem that affects providers and researchers across all disciplines. The coronavirus disease 2019 pandemic has amplified the challenges associated with burnout. Supporting the needs and promoting the well-being of people, therefore, are critical to move forward successfully. At the same time, the scientific advances in our field rely on sound scientific principles and integrity. Information overload, pressure to produce immediate outcomes (such as cost-saving initiatives), and misinformation can compromise the scientific process and research evidence. The two common missteps that affect researchers, clinicians, and administrators include premature factulation and binary thinking. We will discuss how these missteps can occur and the approaches to minimize their influence in making sound decisions and policies to meet the future's needs.

Effects of oral clotrimazole troches on the pharmacokinetics of oral and intravenous midazolam.

AIMS: The aim of the study was to determine the effects of oral clotrimazole troches on the pharmacokinetics of oral and intravenous midazolam in the plasma. METHODS: We conducted a randomized, open-label, four-way crossover study in 10 healthy volunteers. Each volunteer received oral midazolam 2 mg or intravenous midazolam 0.025 mg kg(-1) with and without oral clotrimazole troches 10 mg taken three times daily for 5 days. Each study period was separated by 14 days. Serial blood samples were collected up to 24 h after oral midazolam and 6 h after intravenous midazolam. Plasma concentrations for midazolam and its metabolite 1-hydroxymidazolam were measured and fitted to a noncompartmental model to estimate the pharmacokinetic parameters. RESULTS: Ten healthy volunteers aged 21-26 years provided written informed consent and were enrolled into the study. Clotrimazole decreased the apparent oral clearance of midazolam from 57 +/- 13 l h(-1)[95% confidence interval 48, 66] to 36 +/- 9.8 l h(-1) (95% confidence interval 29, 43) (P= 0.003). These changes were accompanied by a decrease in the area under the concentration-time curve (mean difference 22 microg h(-1) l(-1), P= 0.001) and bioavailability (mean difference 0.21, P= NS). There were no significant differences in the systemic clearance of midazolam with or without clotrimazole troches. CONCLUSIONS: Oral clotrimazole troches decreased the apparent oral clearance of midazolam; no significant differences in the systemic clearance of midazolam were found.

Methods for Estimating Energy Expenditure in Critically Ill Adults.

Energy expenditure (EE) is the sum of metabolic activity within the body at a given time and comprises basal EE, diet-induced thermogenesis, and physical activity. In the intensive care unit, EE is most often assessed to determine a patient's caloric requirements. Energy expenditure also may be useful to understand disease states and the metabolic impact of interventions. Several methods for estimating EE are relevant for clinical use, including indirect calorimetry, predictive equations, exhaled carbon dioxide volume, and the Fick method. Indirect calorimetry is the preferred method for evaluating EE and is considered the gold standard for estimating EE in hospitalized patients. However, use of indirect calorimetry is not always practical or possible. Therefore, other methods of estimating EE must be considered. In this review, methods of evaluating EE in critically ill adults are examined and the benefits and limitations of each method are discussed, with practical considerations for use.

The Impact of Proximal Roux-en-Y Gastric Bypass Surgery on Acetaminophen Absorption and Metabolism.

BACKGROUND: Roux-en-Y gastric bypass (RYGBS), a surgery that creates a smaller stomach pouch and reduces the length of small intestine, is one of the most common medical interventions for the treatment of obesity. AIM: The aim of this study was to determine how RYGBS affects the absorption and metabolism of acetaminophen. MATERIALS AND METHODS: Ten morbidly obese patients received 1.5 g of liquid acetaminophen (APAP) orally on three separate pharmacokinetic study days (i.e., pre-RYGBS baseline and 3 and 12 months post-RYGBS). Plasma was collected at pre-specified timepoints over 24 hours, and the samples were analyzed using liquid chromatography-mass spectrometry for APAP, APAPglucuronide (APAP-gluc), APAP-sulfate (APAP-sulf), APAP-cysteine (APAP-cys), and APAP-Nacetylcysteine (APAP-nac). RESULT: Following RYGBS, peak APAP concentrations at the 3-month and 12-month visits increased by 2.0-fold compared to baseline (p=0.0039 and p=0.0078, respectively) and the median time to peak concentration decreased from 35 to 10 minutes. In contrast, peak concentrations of APAP-gluc, APAP-sulf, APAP-cys, and APAP-nac were unchanged following RYGBS. The apparent oral clearance of APAP and the ratios of metabolite area under the curve (AUC)-to-APAP AUC for all four metabolites decreased at 3 and 12 months post-RYGBS compared to the presurgical baseline. In a simulation of expected steady-state plasma concentrations following multiple dosing of 650 mg APAP every 4 hours, post-RYGBS patients had higher steady-state peak APAP concentrations compared to healthy individuals and obese pre-RYGBS patients, though APAP exposure was unchanged compared to healthy individuals. CONCLUSION: Following RYGBS, the rate and extent of APAP absorption increased and decreased formation of APAP metabolites was observed, possibly due to downregulation of Phase II and cytochrome P450 2E1 enzymes.

Value of Nutrition Support Therapy: Impact on Clinical and Economic Outcomes in the United States.

OBJECTIVE: Healthcare leaders seek guidance on prudent investment in programs that improve patient outcomes and reduce costs, which includes the value of nutrition therapy. The purpose of this project was to conduct an evidence review and evaluate claims analyses to understand the financial and quality impact of nutrition support therapy on high-priority therapeutic conditions. METHODS: Task 1 included a review of existing literature from 2013 to 2018 to identify evidence that demonstrated the clinical and economic impact of nutrition intervention on patient outcomes across 13 therapeutic areas (TAs). In Task 2, analytic claims modeling was performed using the Medicare Parts A and B claims 5% sample dataset. Beneficiaries diagnosed in 5 selected TAs (sepsis, gastrointestinal [GI] cancer, hospital-acquired infections, surgical complications, and pancreatitis) were identified in the studies from Task 1, and their care costs were modeled based on nutrition intervention. RESULTS: Beginning with 1099 identified articles, 43 articles met the criteria, with a final 8 articles used for the Medicare claims modeling. As examples of the modeling demonstrated, the use of advanced enteral nutrition formula could save at least $52 million annually in a sepsis population. The total projected annual cost savings from the 5 TAs was $580 million. CONCLUSION: Overall, optimization of nutrition support therapy for specific patient populations is estimated to reduce Medicare spending by millions of dollars per year across key TAs. These findings demonstrate the evidence-based value proposition of timely nutrition support to improve clinical outcomes and yield substantial cost savings.

Copper Deficiency in Liver Diseases: A Case Series and Pathophysiological Considerations.

Copper is an indispensable trace element. It serves as a cofactor for enzymes involved in cellular energy metabolism, antioxidant defense, iron transport, and fibrogenesis. Although these processes are central in the pathogenesis of liver disorders, few studies have attributed them to copper deficiency. We herein describe in detail a case series of liver disease patients (n = 12) who presented with signs of copper deficiency based on serum and liver copper measurements. Median age of the group at the time of presentation was 39 (range 18-64 years). Six patients were female. The median serum copper was 46 µg/dL (normal range: 80-155 µg/dL for women and 70-140 µg/dL for men). Seven of the 12 patients had hepatic copper concentration less than 10 µg/g dry weight (normal range: 10-35 µg/g). Most cases presented with acute-on-chronic liver failure (n = 4) and decompensated cirrhosis (n = 5). Only 3 patients had a condition known to be associated with copper deficiency (ileocolonic Crohn's disease following resection n = 1, Roux-en-Y gastric bypass n = 2) before presenting with hepatic dysfunction. Notable clinical features included steatohepatitis, iron overload, malnutrition, and recurrent infections. In 2 of the 3 patients who received copper supplementation, there was an improvement in serum copper, ceruloplasmin, and liver function parameters. Conclusion: Copper deficiency in the serum or liver occurs in a wide range of liver diseases. Given the biological essentiality of copper, the mechanism and clinical significance of this association require systematic study.

Parenteral Provision of Micronutrients to Adult Patients: An Expert Consensus Paper.

BACKGROUND: Micronutrients, an umbrella term used to collectively describe vitamins and trace elements, are essential components of nutrition. Those requiring alternative forms of nutrition support are dependent on the prescribed nutrition regimen for their micronutrient provision. The purpose of this paper is to assist clinicians to bridge the gap between the available guidelines' recommendations and their practical application in the provision of micronutrients via the parenteral route to adult patients. METHODS: Based on the available evidenced-based literature and existing guidelines, a panel of multidisciplinary healthcare professionals with significant experience in the provision of parenteral nutrition (PN) and intravenous micronutrients developed this international consensus paper. RESULTS: The paper addresses 14 clinically relevant questions regarding the importance and use of micronutrients in various clinical conditions. Practical orientation on how micronutrients should be prescribed, administered, and monitored is provided. CONCLUSION: Micronutrients are a critical component to nutrition provision and PN provided without them pose a considerable risk to nutrition status. Obstacles to their daily provision-including voluntary omission, partial provision, and supply issues-must be overcome to allow safe and responsible nutrition practice.

Effect of intravenous iron supplementation on hepatic cytochrome P450 3A4 activity in hemodialysis patients: a prospective, open-label study.

BACKGROUND: Cytochrome P450 (CYP) 3A4 is an enzyme with activity dependent on the reduction of heme iron that is responsible for the metabolism of many drugs. CYP3A4 activity is reduced in hemodialysis (HD) patients and thus may be related to functional iron deficiency. OBJECTIVE: The purpose of this study was to investigate the effect of IV iron supplementation on hepatic is CYP3A4 activity in HD patients. METHODS: This prospective, open-label study was conducted in 12 iron-deficient (transferrin saturation <20% or ferritin <100 ng/L) HD patients on stable medication regimens. To probe for hepatic CYP3A4 activity, an erythromycin breath test (ERMBT) was administered before and after 1 g IV iron sucrose (administered as a 100-mg dose [20 mg/mL]), at each of 10 consecutive HD sessions). CYP3A4 activity was estimated by the percentage of administered (14)C exhaled in a single-breath collection after the test dose of erythromycin underwent demethylation by CYP3A4. The ERMBT was also administered to 7 age-, sex-, and race-matched healthy controls. RESULTS: Twelve HD patients (6 Hispanic, 3 white, 3 Native American; 8 men, 4 women; mean [SEM] age, 56.2 [5.0] years; mean [SEM] weight, 77.0 [5.6] kg; and 7 controls (4 men, 3 women; mean [SEM] age, 51.3 [5.0] years; mean [SEM] weight, 77.5 [7.4] kg) were enrolled in the study. In the total HD population studied, mean (SEM) CYP3A4 activity did not change significantly after IV iron replacement (1.46 [0.27] vs 1.57 [0.24] (14)C exhaled/h). A subgroup of 7 HD patients had significantly lower CYP3A4 activity before IV iron replacement compared with the other 5 HD patients and controls (mean [SEM] 0.86 [0.24] vs 2.30 [0.26] and 2.10 [0.26] (14)C exhaled/h; P < 0.01). After IV iron replacement, mean (SEM) CYP3A4 activity increased in these 7 HD patients (120.1% [67.1%]); P = 0.04) and it was not statistically different from that of controls (1.50 [0.36] vs 2.10 [0.26]). CONCLUSIONS: Overall, IV iron administration had no significant effect on hepatic CYP3A4 activity. However, in a subset of HD patients with low baseline CYP3A4 activity indicated by low ERMBT values, IV iron supplementation was associated with a potentially clinically relevant increase in hepatic CYP3A4 activity. Further studies are needed to clarify mechanisms and clinical implications of this interaction.

Proposal for a new tool to evaluate drug interaction cases.

The assessment of causation for a potential drug interaction requires thoughtful consideration of the properties of both the object and precipitant drugs, patient-specific factors, and the possible contribution of other drugs that the patient may be taking. The Naranjo nomogram was designed to evaluate single-drug adverse events, not drug-drug interactions. Several of the questions on the Naranjo nomogram do not apply to potential drug-drug interactions, while others do not specify object or precipitant drug. Nevertheless, it has been inappropriately used to evaluate drug-drug interactions. The Drug Interaction Probability Scale (DIPS) was developed to provide a guide to evaluating drug interaction causation in a specific patient. It is intended to be used to assist practitioners in the assessment of drug interaction-induced adverse outcomes. The DIPS uses a series of questions relating to the potential drug interaction to estimate a probability score. An accurate assessment using the DIPS requires knowledge of the pharmacologic properties of both the object and precipitant drugs. Inadequate knowledge of either the drugs involved or the basic mechanisms of interaction will be a limitation for some users. The DIPS can also serve as a guide in the preparation of articles describing case reports of drug interactions, as well as in the evaluation of published case reports.

Indirect calorimetry: a practical guide for clinicians.

This review provides clinicians with a comprehensive overview of indirect calorimetry including the principles, methodology, technologic advancements, benefits, and challenges. Clinical applications for indirect calorimetry and the potential limitations are specifically addressed for both the inpatient and outpatient setting. Measurement of energy expenditure is the most accurate method to assess energy needs. Indirect calorimetry remains a gold standard in measuring energy expenditure in the clinical settings. The benefits of providing optimal nutrition for recovery from illness and chronic health management are well documented. Indirect calorimetry offers a scientifically-based approach to customize a patient's energy needs and nutrient delivery to maximize the benefits of nutrition therapy. With recent advances in technology, indirect calorimeters are easier to operate, more portable, and affordable. Increased utilization of indirect calorimetry would facilitate individualized patient care and should lead to improved treatment outcomes.