Understanding the association between fatigue and neurocognitive functioning in patients with glioma: A cross-sectional multinational study.

Background: Fatigue and neurocognitive impairment are highly prevalent in patients with glioma, significantly impacting health-related quality of life. Despite the presumed association between these two factors, evidence remains sparse. Therefore, we aimed to investigate this relationship using multinational data. Methods: We analyzed data on self-reported fatigue and neurocognitive outcomes from postoperative patients with glioma from the University of California San Francisco (n = 100, UCSF) and Amsterdam University Medical Center (n = 127, Amsterdam UMC). We used multiple linear regression models to assess associations between fatigue and seven (sub)domains of neurocognitive functioning and latent profile analysis to identify distinct patterns of fatigue and neurocognitive functioning. Results: UCSF patients were older (median age 49 vs. 43 years, P = .002), had a higher proportion of grade 4 tumors (32% vs. 18%, P = .03), and had more neurocognitive deficits (P = .01). While the number of clinically fatigued patients was similar between sites (64% vs. 58%, P = .12), fatigue and the number of impaired neurocognitive domains were not correlated (P = .16-.72). At UCSF, neurocognitive domains were not related to fatigue, and at Amsterdam UMC attention and semantic fluency explained only 4-7% of variance in fatigue. Across institutions, we identified four distinct patterns of neurocognitive functioning, which were not consistently associated with fatigue. Conclusions: Although individual patients might experience both fatigue and neurocognitive impairment, the relationship between the two is weak. Consequently, both fatigue and neurocognitive functioning should be independently assessed and treated with targeted therapies.

Evaluating the Use of Phenobarbital for the Management of Alcohol Withdrawal Syndrome in Psychiatric Inpatients.

OBJECTIVES: To describe the potential role of phenobarbital as appropriate therapy in the treatment and prevention of alcohol withdrawal syndrome (AWS) among medically cleared psychiatric inpatients. METHODS: This was a single-center, retrospective, observational study of adult patients admitted to the psychiatric unit and administered phenobarbital for the treatment or prevention of AWS. Changes in vital signs and signs and symptoms of AWS were observed to assess the safety and efficacy of phenobarbital. The primary outcome was safety of phenobarbital for AWS as measured by change in the respiratory rate (RR). RESULTS: A total of 122 patients were included in the study. There were no significant changes in RR among patients who received phenobarbital for AWS. Significant reductions in blood pressure and heart rate were observed. Of patients with documented signs and symptoms of AWS upon admission, 94% had improvement in the signs and symptoms during phenobarbital therapy. Approximately 12% of patients had documented sedation or altered mental status during phenobarbital therapy. No patients required transfer to a medical or critical care unit. CONCLUSIONS: Phenobarbital was safe, not leading to severe adverse effects or requiring a higher level of care, and efficacious for the prevention and treatment of AWS in this cohort of psychiatric inpatients.

Pharmacy Student Performance in a Capstone Course Utilizing the Pharmacists' Patient Care Process.

Objective. To develop, implement, and assess student performance and confidence in a pharmacy capstone course that used case-based instruction and the Pharmacist's Patient Care Process (PPCP) to develop patient work-up skills in third-year Doctor of Pharmacy (PharmD) students. Methods. A skills-based capstone course was developed by a team of faculty members and instructional designers that focused on patient evaluation skills and applying the steps of the PPCP to complex patient cases housed in a simulated electronic health record (SEHR). The acuity of the cases increased over the course of the semester. For each patient case, students were expected to identify drug-related problems and develop an assessment and plan based on the information provided in the SEHR. Results. Students (n=134) were assessed through weekly quizzes and two practical examinations. The average score for all quizzes was 81%. A significant correlation was found between average quiz scores and performance on the end-of-course practical examination. Student scores significantly improved from the first to the second practical examination (10.4 vs 12.9, respectively), and student confidence with regard to all course objectives significantly improved from the beginning to the end of the semester. Conclusion. A capstone course that applied the PPCP framework successfully taught third-year PharmD students the patient care skills they would need in advanced pharmacy practice experiences.

Using debates as the primary pedagogy to teach critical care in a PharmD curriculum elective course.

BACKGROUND AND PURPOSE: Debate is a pedagogy that incorporates deeper learning and has been used in many areas of healthcare and higher education. Debates have primarily been described within a course, but not as the predominant pedagogy for a course, particularly in pharmacy education or critical care instruction. EDUCATIONAL ACTIVITY AND SETTING: Debating the Evidence was a two-credit hour course taught by debate-style pedagogy on an extended campus to third year pharmacy students in a four-year curricular program. The class met weekly for two hours over 15 weeks, and students came prepared to debate preselected topics. Focus groups for students enrolled over two years were conducted to gauge students' perceptions of this course structure. FINDINGS: The debate-dominant course structure seemed to increase accountability of learning, pre-class preparation, and in-class engagement. Students had difficulty debating with lower quality evidence, but were able to use physiologic reason and adverse effect profiles when robust literature was lacking. All students enrolled over two course offerings consented and participated in the focus groups. Themes identified across both semesters included: 1) efficiency with accessing and evaluating drug literature, 2) increased understanding of an individualized patient-centered approach, and 3) an appreciation for patient care in the acute setting. SUMMARY: An entirely debate-style critical care elective course was perceived to be beneficial to students. Scalability and impact on student learning requires further assessment.

Evaluation of the use of script concordance test in a multicampus psychiatric pharmacy elective course.

INTRODUCTION: Evaluating a student's ability to accept complexity, uncertainty, and ambiguity as part of clinical practice is difficult in a classroom setting using written tests. This study was conducted to explore the feasibility and validation of using a script concordance test (SCT) to evaluate pharmacy student knowledge and clinical competence in a psychiatry elective course. METHODS: This study involved prospective validation of psychiatry-focused SCT questions using a panel of practicing psychiatric pharmacists and retrospective review of student performance on the same SCT questions. The reliability of the SCT was also evaluated using Cronbach alpha coefficient. RESULTS: A total of 13 practicing psychiatric pharmacists participated in the validation phase of the study of 75 questions. Pharmacy student scores (n = 17) averaged 39.79 (±5.02) points, and psychiatric pharmacist scores averaged 50.11 (±4.51) points, representing mean percentages of 61.2% and 77.1%, respectively, on the adjusted exam. The Cronbach alpha was 0.94. DISCUSSION: The development of a valid and reliable SCT to test student psychiatric pharmacy knowledge and clinical competence after taking a psychiatry elective course was feasible.

Neuropsychiatric Symptoms in Dementia: Considerations for Pharmacotherapy in the USA.

Dementia affects all domains of cognition. The relentless progression of the disease after diagnosis is associated with a 98% incidence of neuropsychiatric symptoms (NPS) at some point in the disease, including depression, psychosis, agitation, aggression, apathy, sleep disturbances, and disinhibition. These symptoms can be severe and lead to excess morbidity and mortality. The purpose of this article was to describe current literature on the medication management of NPS of dementia and highlight approaches to and concerns about the pharmacological treatment of NPS in the USA. Guidelines and expert opinion favor nonpharmacologic management of NPS as first-line management. Unfortunately, lack of adequate caregiver training and a high failure rate eventually result in the use of psychotropic agents in patients with dementia. Various psychotropic medications have been studied, although how they should be used in the management of NPS remains unclear. A systematic approach to evaluation, treatment, and monitoring, along with careful documentation and evidenced-based agent and dose selection, is likely to reduce risk and improve patient outcomes. Considerations should be given to the NPS presentation, including type, frequency, and severity, when weighing the risks and benefits of initiating, continuing, or discontinuing psychotropic management. Use of antidepressants, sedative/hypnotics, antipsychotics, and antiepileptic agents should include a clear and documented analysis of risk and benefit in a given patient with dementia.

Rates of new antipsychotic prescriptions and continuation at discharge from a medical unit in a community teaching hospital serving rural counties.

INTRODUCTION: Antipsychotics are commonly used during hospitalization to manage a variety of acute indications and may be inadvertently continued at discharge. The purpose of this study was to identify the rate at which patients admitted to nonpsychiatric units were continued on newly prescribed antipsychotics at discharge from a rural community teaching hospital. METHODS: This study was a retrospective chart review of adult patients admitted to a large community teaching hospital and initiated on an antipsychotic from August 1, 2016, to August 31, 2017. Exclusion criteria were patients admitted to psychiatric or obstetrics/gynecology services, with a diagnosis of a psychotic disorder, or on an antipsychotic prior to hospitalization. The primary outcome measure was the number of new antipsychotic prescriptions during hospitalization that were continued at discharge. Secondary outcomes included antipsychotic characteristics and initiation indications. Descriptive statistics were used to describe antipsychotic use and demographic data. RESULTS: Of 100 patients included, 3 patients were discharged on an antipsychotic. Two patients had questionable indications, and 1 patient had a new psychotic disorder diagnosis. Of all antipsychotics newly initiated during hospitalization, haloperidol was the most commonly prescribed antipsychotic. The majority of doses were scheduled as 1-time or as-needed doses. Approximately 20% of antipsychotics were administered orally. No relevant indication was found for 35% of patients newly initiated on antipsychotics, and documented indications included agitation, psychosis, delirium, and anxiety. DISCUSSION: In an institution that largely serves a rural population, antipsychotic prescribing at discontinuation was not worse than what has been previously reported in other regions of the United States. Limitations for this study include the retrospective nature, single-center study, and small sample size. Although there was a lack of continuation after discharge, there was also a deficit of documentation with 35% of the antipsychotic initiations having no documented indication.

Pain Assessment Documentation After Opioid Administration at a Community Teaching Hospital.

PURPOSE: To compare pain assessment documentation postopioid administration in hospitalized patients before and after implementing nurse education. METHODS: Patients 18 years and older were randomly selected for inclusion if they received 1 opioid dose while admitted to the hospital. Through retrospective chart review, opioid data, including date and time, were collected for each opioid administered. Pain score data, including time and date of documentation, were recorded for analysis. The primary objective of this study was to determine whether a nursing education intervention would improve documentation of pain scores within an appropriate time frame postadministration of an opioid medication. The intervention was a training presentation uploaded to the institution's intranet with an assessment. The primary outcome was measured by comparing the frequency by which nurses documented pain scores following opioid administration before and after education. RESULTS: Three hundred twenty patients (160 patients per time period) were evaluated. The percentage of pain scores recorded within the appropriate assessment time following opioid administration increased from 32.9% to 37.8% ( P = .003). The proportion of appropriate pain score documentation increased 4.9% (95% confidence interval [CI]: 1.6%-8.2%). CONCLUSION: An increase in the documentation of efficacy assessments after opioid administration was demonstrated after nursing education. Further studies should be done to identify additional strategies to increase monitoring as well as to identify a benchmark for institutions with regard to pain management monitoring.

Cases in Psychiatry: A description of a multi-campus elective course for pharmacy students.

Cases in Psychiatry was a multi-campus elective course aimed to expand psychiatry knowledge beyond the required course curriculum. The format of the class included didactic course work, small group discussion of patient cases and article evaluation, submission of written notes, debates, and script concordance test questions delivered via a live online platform. Based on student assessment and feedback at the end of the course, the elective course was determined to meet the prespecified course objectives.

Effect of various antipsychotic regimens on incidence of delirium in critically ill adults.

PURPOSE: Delirium is common during critical illness but it is unknown whether the choice of antipsychotic or dosing strategy impacts delirium outcomes. We evaluated the incidence of delirium in critically ill adults receiving different antipsychotic regimens. MATERIALS AND METHODS: Single center retrospective cohort study of adult patients admitted to the intensive care unit (ICU). Patients who received haloperidol or quetiapine and scored negative on the Confusion Assessment Method for the ICU (CAM-ICU) prior to initiation were included. Patients were divided into four groups based on dosing schedule of the antipsychotic. The primary outcomes were the incidence and duration of delirium. RESULTS: Eighty patients were included in the study. Patients received scheduled quetiapine (35%), PRN haloperidol (55%), and PRN quetiapine (10%). The overall incidence of delirium in patients receiving antipsychotics was 39%. The incidence of delirium was similar between the scheduled quetiapine group, PRN haloperidol and PRN quetiapine groups, at 39%, 50% and 36%, respectively (p=0.79). The scheduled quetiapine group had a longer time to first episode of delirium, but this was not statistically significant (11days vs 4.8days vs 5.6days; p=0.20). CONCLUSIONS: There was no difference in incidence or duration of delirium between quetiapine and haloperidol regimens.

Warfarin and phenytoin drug interaction with possible purple glove syndrome.

Though the impact of phenytoin on warfarin has been reported to potentiate the anticoagulant effect or interact in a biphasic manner, the effect of phenytoin on warfarin appears to be unpredictable and dependent upon multiple factors. Additionally, purple glove syndrome has rarely been reported secondary to therapeutic doses of oral phenytoin. We report on the case of a patient who experienced international normalized ratio (INR) fluctuations upon initiation of warfarin and phenytoin concurrently and who subsequently required discontinuation of therapeutic-dose phenytoin secondary to possible purple glove syndrome.

Medication adherence in patients with schizophrenia.

Medication nonadherence is common among patients with schizophrenia and due to a variety of factors including lack of insight, psychopathology, substance use disorder, issues associated with treatment, stigma, fragmentation of care, cultural influences, and socioeconomic status. Among this population, nonadherence is problematic because it can lead to decompensation or exacerbation of symptoms, relapse, rehospitalization or greater use of emergency psychiatric services, functional decline, and increased risk of death. Psychoeducational approaches alone are ineffective, but in combination with behavioral interventions, appear to be effective. Involving the patient's support system, in addition to other interventions, can improve treatment adherence. Many medication-related factors, such as effectiveness and tolerability of antipsychotics, regimen complexity, and past medication trials impact appropriate medication use. Therefore, optimizing the patient's pharmacotherapeutic regimens can improve adherence. Additional factors favorably influencing adherence include involving the patient in their treatment, fostering a therapeutic alliance, implementing/using reminder systems, and addressing substance use disorder. Medication nonadherence arises from multiple reasons that vary between patients. Thus, the most effective strategies to improve adherence are multifactorial and may involve both psychoeducational and behavioral techniques, as well as previously listed approaches. Strategies should be targeted toward the patient and their support system, whenever possible, to further improve the chances of appropriate medication use. Recognizing that all patients with schizophrenia are at risk for medication nonadherence is important. No one technique has been shown to be most effective; therefore, the risk for nonadherence should continually be assessed and multiple strategies should be targeted to the patient (and caregiver) and repeatedly implemented throughout the course of the patient's illness.

Glucose Disturbances and Atypical Antipsychotic Use in the Intensive Care Unit.

PURPOSE: Chronic use of atypical antipsychotics may lead to metabolic abnormalities including hyperglycemia. Although evidence supports acute hyperglycemic episodes associated with atypical antipsychotic use, the acute use of atypical antipsychotics in the intensive care unit (ICU) setting has not been studied. The purpose of this study is to evaluate the occurrence of hyperglycemia in ICU patients receiving newly prescribed atypical antipsychotic. SUMMARY: Of the 273 patient charts reviewed, 50 patients were included in this study. Approximately 45% of patients experienced at least 1 hyperglycemic episode (blood glucose >180 mg/dL) after the initiation of an atypical antipsychotic in the ICU. Of the patients experiencing at least 1 hyperglycemic episode, 60% experienced multiple distinct hyperglycemic episodes. In this study, quetiapine was the most commonly used atypical antipsychotic, 19 (38%) patients were discharged from the ICU on the atypical antipsychotic, 6 (12%) patients died in the ICU, and 31 (62%) patients were treated with an antihyperglycemic agent. Logistic regression analysis showed that women and ICU patients with a higher Acute Physiology and Chronic Health Evaluation II (APACHE II) score were significantly more likely to have multiple hyperglycemic episodes. CONCLUSION: Patients admitted to the ICU and initiated on an atypical antipsychotic may develop hyperglycemia independent of other glucose-elevating factors. The direct correlation of these agents to resulting acute hyperglycemia is unknown. Further studies are needed to investigate the link between atypical antipsychotics and acute hyperglycemia and the clinical significance of the impact on patient outcomes.

How relevant are assembled equilibrium samples in understanding structure formation during lipid digestion?

Lipid-based formulations are gaining interest for use as drug delivery systems for poorly water-soluble drug compounds. During digestion, the lipolysis products self-assemble with endogenous surfactants in the gastrointestinal tract to form colloidal structures, enabling enhanced drug solubilisation. Although earlier studies in the literature focus on assembled equilibrium systems, little is known about structure formation under dynamic lipolysis conditions. The purpose of this study was to investigate the likely colloidal structure formation in the small intestine after the ingestion of lipids, under equilibrium and dynamic conditions. The structural aspects were studied using small angle X-ray scattering and dynamic light scattering, and were found to depend on lipid composition, lipid chain length, prandial state and emulsification. Incorporation of phospholipids and lipolysis products into bile salt micelles resulted in swelling of the structure. At insufficient bile salt concentrations, a co-existing lamellar phase was observed, due to a reduction in the solubilisation capacity for lipolysis products. Emulsification accelerated the rate of lipolysis and structure formation.

A literature review of quetiapine for generalized anxiety disorder.

To evaluate the efficacy and tolerability of quetiapine for the treatment of generalized anxiety disorder (GAD), a literature search of the Medline database was conducted from inception to May 2014. The search was not restricted by language. Keywords used in the search were quetiapine and generalized anxiety disorder or anxiety. All studies assessing the use of quetiapine as monotherapy or adjunct therapy for the primary management of GAD in adults 18-65 years of age were included in this review. The nine studies included in this review were three studies evaluating the use of quetiapine extended release (XR) as monotherapy for acute GAD treatment, one study evaluating quetiapine XR monotherapy for maintenance treatment of GAD, and five studies evaluating quetiapine (2 XR, 3 immediate release) as adjunct therapy for acute GAD treatment. Quetiapine displayed both efficacy and tolerability in all monotherapy trials evaluating its use for acute and long-term treatment of GAD. Despite some limitations to and heterogeneity among the five adjunct therapy studies, three studies showed that quetiapine resulted in statistically significant changes in the Hamilton Anxiety Rating Scale or Clinical Global Impressions-Severity of Illness Scale scores. Although future studies of longer duration with broader inclusion criteria are needed to further evaluate the benefits and risks of quetiapine for GAD, in patients failing to respond to conventional antidepressant therapy, quetiapine may be a potential treatment option. With appropriate monitoring and management of adverse effects, the potential benefits of quetiapine in patients with treatment-refractory GAD may outweigh the risks associated with its use.

Immobilised lipase for in vitro lipolysis experiments.

In vitro lipolysis experiments are used to assess digestion of lipid-based formulations, and probe solubilisation by colloidal phases during digestion. However, proteins and other biological components in the pancreatin often used as the lipase result in high-background scattering when interrogating structures using scattering approaches, complicating the resolution of colloidal structures. In this study, to circumvent this problem, a modified in vitro digestion model employing lipase immobilised on polymer beads, which allows for separation of the lipid digestion components during lipolysis, was investigated. Titration of the fatty acids released during digestion of medium chain triglycerides using pancreatin compared with immobilised lipase, combined with HPLC was used to follow the digestion, and small-angle X-ray scattering was used to determine colloidal structure formation. Digestion of medium chain triglycerides at the same nominal activity revealed that for the immobilised lipase, a longer digestion time was required to achieve the same extent of digestion. However, the same structural endpoint was observed, indicating that structure formation was not affected by the choice of lipase used. Lipolysis with immobilised lipase led to the reduction of parasitic scattering, resulting in clearer and more defined scattering from the structures generated by the lipolysis products.

Ziconotide-induced psychosis: a case report.

Ziconotide is used intrathecally in the management of severe chronic pain that contains a warning against neuropsychiatric adverse events. The definition of psychiatric events is broad and management strategies are vague. This case report describes a 49-year-old female who was admitted to the acute psychiatric unit to address auditory hallucinations and paranoid ideation persisting for 3 weeks. Approximately 3 months ago, an intrathecal pump with ziconotide was implanted to treat pain. Upon hospital admission, the pump was infusing at a rate of 4.9 mcg/24 hours. Because the drug could not be immediately discontinued, risperidone 0.5 mg nightly was initiated and subsequently, the pump was drained of ziconotide, rinsed, and refilled with normal saline. The patient reported no hallucinations or apparent delusions several hours later and was eventually discharged with resolution of psychotic symptoms and continuation of risperidone for 10 days. Despite the identification of neuropsychiatric effects, limited information is available to characterize the presentation and guide specific management aside from recommendations to discontinue the infusion and possible use of psychotropic medications or necessity for hospitalization. This case report characterizes one presentation of hallucinations and paranoia associated with ziconotide intrathecal infusion. Clinicians should be aware of the management strategies to mediate these adverse effects, including expected time to adverse effect resolution, removal of ziconotide from the pump, and role for short-term use of antipsychotics.

Self-assembly structure formation during the digestion of human breast milk.

An infant's complete diet, human breast milk, is the basis for its survival and development. It contains water-soluble and poorly water-soluble bioactive components, metabolic messages, and energy, all of which are made bioavailable during the digestion process in the infant's gastrointestinal tract. Reported is the first discovery of highly geometrically organized structures formed during the digestion of human breast milk under simulated in vivo conditions using small-angle X-ray scattering and cryogenic transmission electron microscopy. Time of digestion, pH, and bile salt concentration were found to have symbiotic effects gradually tuning the oil-based environment inside the breast milk globules to more water-like structures with high internal surface area. The structure formation is necessarily linked to its function as carriers for poorly water-soluble molecules in the digestive tract of the infant.

Disposition and crystallization of saturated fatty acid in mixed micelles of relevance to lipid digestion.

During lipolysis of triglyceride by lipase, monoglyceride and fatty acids are produced which combine with gastrointestinal fluids to form self-assembled structures. These solubilize hydrophobic food components to promote their absorption. The aim of this study was a detailed understanding of structure formation from triglyceride digestion products with saturated short-, medium- and long chain fatty acids. Complementary characterization methods have been applied comprising small angle X-ray and neutron scattering ­ the latter involving the contrast matching technique using fully deuterated fatty acids ­ polarized and depolarized dynamic light scattering and cryogenic-transmission electron microscopy. Shape, size and solubilization capacity of the self-assembled structures was dependent on composition and lipid chain length. Crystallization of fatty acid was observed when the solubility limit in the mixed bile salt micelles was exceeded; however, increasing pH and temperature increased the fatty acid solubility. The results provide insight into structure formation and crystallization of incorporated lipolysis products; this is important for a detailed understanding of food structure and nutrition, as well as the rational design of lipid based drug delivery systems.