Cannabidiol: A New Hope for Patients With Dravet or Lennox-Gastaut Syndromes.

OBJECTIVE: To review the efficacy, safety, pharmacology and pharmacokinetics of pure, plant-derived cannabidiol (CBD; Epidiolex) in the treatment of Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS). DATA SOURCES: Relevant information was identified through EMBASE and Ovid MEDLINE (1946 to October 2018). Product labeling and https://www.clinicaltrials.gov were also reviewed. STUDY SELECTION/DATA EXTRACTION: English language articles evaluating efficacy and safety in humans with treatment-resistant epilepsies were reviewed; additional pharmacology and pharmacokinetic studies in humans, animals, and in vitro were also included. DATA SYNTHESIS: Pure, plant-based CBD is a pharmaceutical grade extract that exhibits clinically significant antiseizure properties, with a hypothesized multimodal mechanism of action. In the GWPCARE trial series, CBD displayed superior efficacy in reducing key seizure frequencies (convulsive seizures in DS; drop seizures in LGS) by 17% to 23% compared with placebo as adjunctive therapy to standard antiepileptic drugs in patients 2 years of age and older. Common adverse effects were somnolence, diarrhea, and elevated hepatic transaminases. Noteworthy drug-drug interactions included clobazam, valproates, and significant inducers/inhibitors of CYP2C19 and 3A4 enzymes. Relevance to Patient Care and Clinical Practice: A discussion regarding CBD dosing, administration, adverse effects, monitoring parameters, and interactions is provided to guide clinicians. CBD offers patients with DS and LGS a new treatment option for refractory seizures. CONCLUSION: This is the first cannabis-derived medication with approval from the US Food and Drug Administration. This CBD formulation significantly reduces seizures as an adjunct to standard antiepileptic therapies in patients ≥2 years old with DS and LGS and is well tolerated.

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.

Significant Published Articles for Pharmacy Nutrition Support Practice in 2014 and 2015.

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.

Parenteral nutrition insecurity: ASPEN survey to assess the extent and severity of parenteral nutrition access and reimbursement issues.

BACKGROUND: Parenteral nutrition (PN) shortages and lack of qualified professional staff to manage PN impact safe, efficacious care and costs of PN. This American Society for Parenteral and Enteral Nutrition (ASPEN)-sponsored survey assessed the frequency and extent to which PN access affects PN delivery to patients. METHODS: Healthcare professionals involved with PN were surveyed. Questions were developed to characterize the respondent population and determine the extent and severity of PN access issues to components, devices, and healthcare professionals, as well as their effects on discharge and transfer issues. Reimbursement issues included cost, adequacy of therapy, and healthcare professional reimbursement. Burdens were types and frequency of errors, adverse events, and nutrition problems resulting from PN access issues. Impact on professionals and organizations was determined. RESULTS: Respondents (N = 350) worked in hospitals (75%) and home infusion (25%). Per day, clinicians cared for <15 patients receiving PN. All age populations were represented. Respondents reported shortages of macronutrients (72%, 233 of 324) and micronutrients (91%, 297 of 324). Issues with access to healthcare workers were observed. PN access issues contribute to increased costs of PN, and knowledge regarding the current rate of PN reimbursement is limited. Respondents (75%, 197 of 261) observed an error due to PN access issues. Adverse events (57%, 149 of 259) were observed leading to temporary or permanent harm (24%, 61 of 259) as well as near death (4%, 9 of 259) and death (1%, 2 of 259). Providers reported time away from other job responsibilities and workplace stress. CONCLUSION: PN access issues result in "PN insecurity" that negatively impacts patients and healthcare providers and leads to adverse events including death in patients receiving PN.

Prevention of Parenteral Nutrition-associated Cholestasis Using Reduced Dose Soybean Lipid Emulsion: A Multicenter Randomized Trial.

INTRODUCTION: Reducing soybean lipid emulsion (SLE) dose may prevent parenteral nutrition-associated cholestasis (PNAC) but effects on growth and neurodevelopment are unknown. The purpose of this study was to evaluate the effect of reduced dose SLE on growth and neurodevelopment. METHODS: Surgical neonates at 4 centers were randomized to standard SLE (3 g/kg/day) or reduced SLE (1 g/kg/day) over a 12-week period. Bilirubin levels and growth parameters were measured baseline and weekly while on study. The effects of time and group on direct bilirubin and growth were evaluated with a linear mixed effects model. Neurodevelopmental outcomes were assessed at 12- and 24-months corrected gestational age. RESULTS: Twenty-one individuals were randomized (standard dose = 9, reduced dose = 12). Subjects in the reduced dose group had slower rates of direct bilirubin increase and overall levels decreased earlier than those in the standard dose group. There was a trend toward a faster direct bilirubin decrease in the reduced dose group (p = 0.07 at day 84). There were no differences in the rates of change in weight (p = 0.352 at day 84) or height Z-scores (p = 0.11 at day 84) between groups. One subject in the reduced dose group had abnormal neurodevelopmental testing at 24 months. CONCLUSIONS: Surgical neonates randomized to a reduced dose of SLE had improved trends in direct bilirubin levels without clinically significant differences in overall growth and neurodevelopment. TYPE OF STUDY: Randomized Controlled Trial. LEVEL OF EVIDENCE: II.

Current nutrition assessment practice: A 2022 survey.

BACKGROUND: Malnutrition remains a significant problem in patients with acute or chronic illnesses. Nutrition assessment is an important component in detecting malnutrition; but not always performed using a standardized tool. This survey on nutrition assessment evaluates current clinical practices on the assessment, diagnosis, and treatment of malnutrition. METHODS: This 2022 survey of US-based nutrition clinicians collected data on assessment parameters used in hospitals, long-term care facilities, and the home care setting. RESULTS: A total of 686 surveys were available for analysis. Ninety-seven percent of adult and 91% of pediatric responding clinicians indicated that a dietitian completed the assessment. Parameters used most frequently among adult clinician respondents included nutrient intake, current weight, and weight history, those used by pediatric clinician respondents included nutrient intake, weight-for-age z score, and weight-for-length/height z score. Eighty-nine percent of adult clinicians in all care settings and 85% of pediatric clinicians use the Academy of Nutrition and Dietetics/American Society for Parenteral and Enteral Nutrition Indicators of Malnutrition (AAIM). Respondents reported malnutrition rates of 32%-40% for adults and 4%-30% for pediatric patients, depending on the setting. Appropriate interventions for those with malnutrition (as perceived by the survey respondents) were ordered 70% of the time. CONCLUSION: This survey demonstrated significant use of the AAIM by both adult and pediatric clinicians across care settings. Reported malnutrition rates are consistent with others published in the literature. The authors suggest that quality improvement efforts should focus on the 30% of patients with malnutrition but without a reported appropriate nutrition intervention.

Blenderized tube feedings: Practice recommendations from the American Society for Parenteral and Enteral Nutrition.

Prior to the 1970s, blending food and liquids and putting them through an enteral access device (EAD) was the most common form of enteral nutrition (EN). However, in the 1970s, blenderized tube feedings (BTFs) became less popular due to the emergence of modern commercial enteral formulas (CEFs). Recently, a cultural shift toward consuming a natural diet, consisting of whole foods, has led to a resurgence in the use of BTF. The increasing use of BTF in a variety of patient care settings identifies a need for practice recommendations that provide guidance for nutrition professionals and patients. Members of the American Society for Parental and Enteral Nutrition (ASPEN) Enteral Nutrition Committee identified salient clinical questions concerning BTF, conducted a comprehensive literature search, and subsequently developed practice recommendations pertaining to the use of BTF. This paper was approved by the ASPEN 2022-2023 Board of Directors.

Pharmacological Management of Pediatric Clostridioides difficile Infection: Clarifying the Controversies.

Clostridioides difficile infection (CDI) is a major public health concern for pediatric and adult patients. The management of pediatric CDI poses a challenge to healthcare providers due to lack of strong randomized controlled trials to guide pharmacological management. Additionally, recent updates to CDI guidelines recommend oral vancomycin over metronidazole for the management of CDI in adults, leaving questions regarding how to best manage pediatric patients. This continuing education pharmacotherapy review describes available evidence for the safety and efficacy of medications used in the treatment and management of pediatric CDI and aims to clarify discrepancies between pediatric and adult recommendations.

Treatment-Refractory Dravet Syndrome: Considerations for Novel Medications.

Before 2018, there were no U.S. Food and Drug Administration-approved medications for managing seizures in Dravet syndrome (DS). Common agents used in the antiepileptic drug regimens of patients with DS included clobazam, valproic acid, topiramate, and levetiracetam, among others; however, these agents alone rarely provide adequate seizure control. Management of seizures in DS changed in recent years with the approval of cannabidiol and stiripentol in 2018 and fenfluramine in 2020. This continuing education article summarizes available efficacy and safety data involving cannabidiol, stiripentol, and fenfluramine and provides a practical review of dosing strategies, pharmacokinetics, and monitoring interventions relevant to their use.

Update on use of enteral and parenteral nutrition in hospitalized patients with a diagnosis of malnutrition in the United States.

BACKGROUND: Malnutrition continues to be associated with outcomes in hospitalized patients. METHODS: An updated review of national data in patients with a coded diagnosis of malnutrition (CDM) and the use of nutrition support (enteral nutrition [EN] and parenteral nutrition [PN]) was conducted using the Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project and Medicare Claims data. RESULTS: Results demonstrated a growing trend in CDM accompanied by continued low utilization of PN and EN. CONCLUSION: Underutilization of nutrition support may be due to product shortages, reluctance of clinicians to use these therapies, undercoding of nutrition support, strict adherence to published guidelines, and other factors.

Allowable room temperature excursions for refrigerated medications: A 20-year review.

PURPOSE: The aim of this review was to build upon previous literature describing the maximum duration for which refrigerated medications can tolerate room temperature excursions while maintaining stability and potency. METHODS: During a 12-month period ending in June 2021, the prescribing information and published monographs from multiple pharmacy compendia were reviewed for all medications and biologic products approved by the US Food and Drug Administration (FDA) for human use since January 2000. Products that were subsequently withdrawn from the US market were excluded. When temperature excursion data was unavailable in published form, product manufacturers were surveyed via telephone and/or email. Acceptable storage information for all products for which storage is recommended at temperatures below room temperature (20-25 °C [68-77 °F]) was compiled and arranged in tabular format. RESULTS: Of the 705 products or formulations approved by FDA during the predefined time period, 246 were identified as requiring storage at temperatures below room temperature. After review of available prescribing information and manufacturer communications, if applicable, acceptable periods of excursion to temperatures at room temperature or higher were identified for 214 products (87%). CONCLUSION: Information related to acceptable periods of room temperature excursion was compiled for a total of 214 products approved for US distribution since 2000. The included tables may increase patient safety and decrease medication loss or related expenditures.

Optimizing the nutrition support care model: Analysis of survey data.

BACKGROUND: Malnutrition is underrecognized and underdiagnosed, despite high prevalence rates and associated poor clinical outcomes. The involvement of clinical nutrition experts, especially physicians, in the care of high-risk patients with malnutrition remains low despite evidence demonstrating lower complication rates with nutrition support team (NST) management. To facilitate solutions, a survey was designed to elucidate the nature of NSTs and physician involvement and identify needs for novel nutrition support care models. METHODS: This survey assessed demographics of NSTs, factors contributing to the success of NSTs, elements of nutrition education, and other barriers to professional growth. RESULTS: Of 255 respondents, 235 complete surveys were analyzed. The geographic distribution of respondents correlated with population concentrations of the United States (r = 90.8%, p < .0001). Most responding physicians (46/57; 80.7%) reported being a member of NSTs, compared with 56.5% (88/156) of dietitians. Of those not practicing in NSTs (N = 81/235, 34.4%), 12.3% (10/81) reported an NST was previously present at their institution but had been disbanded. Regarding NSTs, financial concerns were common (115/235; 48.9%), followed by leadership (72/235; 30.6%), and healthcare professional (HCP) interest (55/235; 23.4%). A majority (173/235; 73.6%) of all respondents wanted additional training in nutrition but reported insufficient protected time, ability to travel, or support from administrators or other HCPs. CONCLUSION: Core actions resulting from this survey focused on formalizing physician roles, increasing interdisciplinary nutrition support expertise, utilizing cost-effective screening for malnutrition, and implementing intervention protocols. Additional actions included increasing funding for clinical practice, education, and research, all within an expanded portfolio of pragmatic nutrition support care models.

Perceived Versus Demonstrated Understanding of the Complex Medications of Medically Complex Children.

OBJECTIVES: Parents and caregivers of children with medical complexity (CMC) manage complex medication regimens (CMRs) at home. Parental understanding of CMRs is critical to safe medication administration. Regarding CMR administration, we 1) described the population of CMC receiving CMRs; 2) assessed parental perceived confidence and understanding; and 3) evaluated parental demonstrated understanding. METHODS: Cross-sectional clinic-based assessment of knowledge and understanding of CMC using CMRs who received primary care in a large pediatric complex care clinic. CMRs were identified by the receipt of ≥1 of the following: 1) ≥10 concurrent medications; 2) ≥1 high-risk medication; or 3) ≥1 extemporaneously compounded medication. Parents reported their perceived confidence and understanding of CMRs, and then demonstrated understanding through 3 medication-related tasks. RESULTS: Of 156 CMCs, most were <10 years of age (63.5%), white (75%), had neurologic impairment (76.9%), and used a median of 8 medications (IQR, 5-10). Parents were female (76.9%) with a mean age of 38.8 ± 11.5 years, white (69.9%), spoke English (94.2%), and had some college education (82.1%). On 11 confidence and understanding statements, most parents reported a high perceived level of understanding and confidence, with combined agreement or strong agreement ranging between 81.2% and 98.7%. Only 73.1% correctly identified medications taken for specified conditions, 40.4% reported complete dosing parameters, and 54.8% correctly measured 2 different medication doses. Significant differences existed between parental perceived understanding versus the 3 demonstrated tasks (all p < 0.05). CONCLUSIONS: Substantial opportunities exist to improve medication safety and efficacy in the outpatient, in-home setting including improved medication-specific education and medication-related supports.

Complexity of Medication Regimens for Children With Neurological Impairment.

Importance: Parents of children with severe neurological impairment (SNI) manage complex medication regimens (CMRs) at home, and clinicians can help support parents and simplify CMRs. Objective: To measure the complexity and potentially modifiable aspects of CMRs using the Medication Regimen Complexity Index (MRCI) and to examine the association between MRCI scores and subsequent acute visits. Design, Setting, and Participants: This cross-sectional study was conducted between April 1, 2019, and December 31, 2020, at a single-center, large, hospital-based, complex care clinic. Participants were children with SNI aged 1 to 18 years and 5 or more prescribed medications. Exposure: Home medication regimen complexity was assessed using MRCI scores. The total MRCI score is composed of 3 subscores (dosage form, dose frequency, and specialized instructions). Main Outcomes and Measures: Patient-level counts of subscore characteristics and additional safety variables (total doses per day, high-alert medications, and potential drug-drug interactions) were analyzed by MRCI score groups (low, medium, and high score tertiles). Associations between MRCI score groups and acute visits were tested using Poisson regression, adjusted for age, complex chronic conditions, and recent health care use. Results: Of 123 patients, 73 (59.3%) were male with a median (interquartile range [IQR]) age of 9 (5-13) years. The median (IQR) MRCI scores were 46 (35-61 [range, 8-139]) overall, 29 (24-35) for the low MRCI group, 46 (42-50) for the medium MRCI group, and 69 (61-78) for the high MRCI group. The median (IQR) counts for the subscores were 6 (4-7) dosage forms per patient, 7 (5-9) dose frequencies per patient, and 5 (4-8) instructions per patient, with counts increasing significantly across higher MRCI groups. Similar trends occurred for total daily doses (median [IQR], 31 [20-45] doses), high-alert medications (median [IQR], 3 [1-5] medications), and potential drug-drug interactions (median [IQR], 3 [0-6] interactions). Incidence rate ratios of 30-day acute visits were 1.26 times greater (95% CI, 0.57-2.78) in the medium MRCI group vs the low MRCI group and 2.42 times greater (95% CI, 1.10-5.35) in the high MRCI group vs the low MRCI group. Conclusions and Relevance: Higher MRCI scores were associated with multiple dose frequencies, complicated by different dosage forms and instructions, and associated with subsequent acute visits. These findings suggest that clinical interventions to manage CMRs could target various aspects of these regimens, such as the simplification of dosing schedules.

Malnutrition diagnoses and associated outcomes in hospitalized patients: United States, 2018.

In the US, malnutrition is prevalent among hospitalized patients and is associated with higher morbidity, mortality, and healthcare costs when compared with those without malnutrition. Over time, national data have indicated the rate of coded malnutrition diagnoses among hospital discharges rising over time, and more current data on demographic and clinical characteristics of these patients are needed. Data on malnutrition discharges from the 2018 Healthcare Cost and Utilization Project (HCUP)-the most recent nationally representative data-were examined and compared with earlier HCUP findings. Based on International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes, 8.9% of all US non-maternal, non-neonatal hospital discharges in 2018 had a coded diagnosis of malnutrition (CDM). From this 2018 data, those with a CDM were older, had longer lengths of stay, and incurred higher costs, as compared with those without a CDM. Higher readmission rates and higher inpatient mortality were also observed in this group. These findings provide more recent demographic and clinical evidence for standardized malnutrition diagnostic and interventional programs to treat and/or prevent this condition.

Providers' perspectives on the clinical utility of pharmacogenomic testing in pediatric patients.

Aim: To assess providers' knowledge, attitudes, perceptions, and experiences related to pharmacogenomic (PGx) testing in pediatric patients. Materials & methods: An electronic survey was sent to multidisciplinary healthcare providers at a pediatric hospital. Results: Of 261 respondents, 71.3% were slightly or not at all familiar with PGx, despite 50.2% reporting prior PGx education or training. Most providers, apart from psychiatry, perceived PGx to be at least moderately useful to inform clinical decisions. However, only 26.4% of providers had recent PGx testing experience. Unfamiliarity with PGx and uncertainty about the clinical value of testing were common perceived challenges. Conclusion: Low PGx familiarity among pediatric providers suggests additional education and electronic resources are needed for PGx examples in which data support testing in children.

Importance of public-private partnerships for nutrition support research: An ASPEN Position Paper.

Parenteral and enteral nutrition support are key components of care for various medical and physiological conditions in infants, children, and adults. Nutrition support practices have advanced over time, driven by the goals of safe and sufficient delivery of needed nutrients and improved patient outcomes. These advances have been, and continue to be, dependent on research and development studies. Such studies address aspects of enteral and parenteral nutrition support: formulations, delivery devices, health outcomes, cost-effectiveness, and related metabolism. The studies are supported by public funding from the government and by private funding from foundations and from the nutrition support industry. To build public trust in nutrition support research findings, it is important to underscore ethical research conduct and reporting of results for all studies, including those with industry sponsors. In 2019, American Society for Parenteral and Enteral Nutrition's (ASPEN's) Board of Directors established a task force to ensure integrity in nutrition support research that is done as collaborative partnerships between the public (government and individuals) and private groups (foundations, academia, and industry). In this ASPEN Position Paper, the Task Force presents principles of ethical research to guide administrators, researchers, and funders. The Task Force identifies ways to curtail bias and to minimize actual or perceived conflict of interests, as related to funding sources and research conduct. Notably, this paper includes a Position Statement to describe the Task Force's guidance on Public-Private Partnerships for research and funding. This paper has been approved by the ASPEN Board of Directors.

Pharmacological Management of Spasticity in Children With Cerebral Palsy.

Cerebral palsy (CP), a nonprogressive disease of the central nervous system, is the most common motor disability in childhood. Patients with CP often have a multitude of associated comorbidities, including impact on muscle tone. There are four main types of CP, with spastic as the most commonly diagnosed. Reduction in spasticity is important because it can affect not only the patient's quality of life, functional abilities, and well-being but also the lives of caregivers. The American Academy of Neurology and Child Neurology Society released a practice parameter regarding the pharmacological management of CP-related spasticity in 2010. Since then, data have been published evaluating the safety and efficacy of oral and parenteral medications to manage spasticity. This continuing education review evaluates the available safety and efficacy evidence for oral and parenteral pharmacological agents used to reduce spasticity in children with CP and provides a reference for practitioners managing these patients.