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.

pH-responsive micelles based on caprylic acid.

Free fatty acids play a vital role as fuel for cells and in lipid metabolism. During lipid digestion in the gastrointestinal tract, triglycerides are hydrolyzed, resulting in free fatty acid and monoglyceride amphiphilic products. These components, together with bile salts, are responsible for the transport of lipids and poorly water-soluble nutrients and xenobiotics from the intestine into the circulatory system of the body. In this study, we show that the self-assembly of digestion products from medium-chain triglycerides (tricaprylin) in combination with bile salt and phospholipid is highly pH-responsive. Individual building blocks of caprylic acid within the mixed colloidal structures are mapped using a combination of small-angle X-ray and neutron scattering combined with both solvent contrast variation and selective deuteration. Modeling of the scattering data shows transitions in the size and shape of the micelles in combination with a transfer of the caprylic acid from the core of the micelles to the shell or into the bulk water upon increasing pH. The results help to understand the process of lipid digestion with a focus on colloidal structure formation and transformation for the delivery of triglyceride lipids and other hydrophobic functional molecules.

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.

Structural aspects of digestion of medium chain triglycerides studied in real time using sSAXS and Cryo-TEM.

PURPOSE: The purpose of this study was to investigate the colloidal structures formed on digestion of medium chain triglyceride (MCT) with a specific objective of identifying and characterizing a previously reported vesicular phase, which has been linked to supersaturation and anomalous digestion kinetics, and to evaluate the influence of lipid mass and enzyme inhibition on self assembled structure. METHODS: MCT was digested in vitro and nanostructure was monitored in real time using synchrotron small angle X-ray scattering (sSAXS), and morphology was studied using cryogenic transmission electron microscopy (cryo-TEM). RESULTS: Formation of the putative vesicular phase formed on digestion of MCT was confirmed and its structural attributes were determined. Vesicle formation was dependent on lipid mass and bile salt concentration. The use of enzyme inhibitor for offline analysis of lipolysis samples did influence structural aspects of the digestion medium when compared to real time evaluation. CONCLUSIONS: The formation of a vesicular phase was directly linked to the kinetics of lipid digestion. Vesicle formation is linked to lipid mass, or more specifically the ratio of lipid to bile salts present in the digestion mixture. Inhibition of lipase to halt digestion during sampling for offline analysis must be done with caution as structural aspects were shown to differ for the MCT digests with and without inhibitor present.

Functional language networks in sedentary and physically active older adults.

Functional magnetic resonance imaging (fMRI) studies have identified consistent age-related changes during various cognitive tasks, such that older individuals display more positive and less negative task-related activity than young adults. Recently, evidence shows that chronic physical exercise may alter aging-related changes in brain activity; however, the effect of exercise has not been studied for the neural substrates of language function. Additionally, the potential mechanisms by which aging alters neural recruitment remain understudied. To address these points, the present study enrolled elderly adults who were either sedentary or physically active to characterize the neural correlates of language function during semantic fluency between these groups in comparison to a young adult sample. Participants underwent fMRI during semantic fluency and transcranial magnetic stimulation to collect the ipsilateral silent period, a measure of interhemispheric inhibition. Results indicated that sedentary older adults displayed reductions in negative task-related activity compared to the active old group in areas of the attention network. Longer interhemispheric inhibition was associated with more negative task-related activity in the right and left posterior perisylvian cortex, suggesting that sedentary aging may result in losses in task facilitatory cortical inhibition. However, these losses may be mitigated by regular engagement in physical exercise.

Prolonged sinus pauses with hydromorphone in the absence of cardiac conduction disease.

A 49-year-old male had open sigmoid colectomy with colorectal anastomosis for sigmoid diverticulitis. The patient was given patient-controlled analgesia (PCA) hydromorphone and subsequently developed bradycardia with prolonged sinus pauses up to 7.1 seconds. The pauses resolved shortly after the hydromorphone was discontinued. This is the first case report to our knowledge of reversible prolonged sinus pauses associated with the use of hydromorphone. Animal studies support a role for opioid signaling at the sinoatrial (SA) node. Hydromorphone is a potential cause of prolonged sinus pauses and should be taken into consideration when monitoring a patient on hydromorphone for pain control.

Symptomatic bradycardia with oral aripiprazole and oral ziprasidone.

OBJECTIVE: To describe the case of a patient who developed symptomatic bradycardia upon initiation of oral ziprasidone and later with oral aripiprazole, both of which resolved shortly after discontinuation of therapy. CASE SUMMARY: An 18-year-old female with bipolar disorder was started on oral ziprasidone 80 mg at night and the dose was subsequently increased to 120 mg for management of acute mania and delusions. The patient developed symptomatic bradycardia (heart rate 31-35 beats/min), which resolved after ziprasidone was decreased to 80 mg. Three months later, the patient was readmitted for treatment of bipolar mania with psychotic features in the context of medication nonadherence. She was started on oral aripiprazole 15 mg daily (subsequently increased to 20 mg) in conjunction with 600 mg lithium carbonate twice daily. The patient again developed symptomatic bradycardia that resolved after discontinuation of aripiprazole. DISCUSSION: This is the first case report of symptomatic bradycardia associated with the use of ziprasidone or aripiprazole. The Naranjo probability scale suggests that the likelihood of the atypical antipsychotic as the cause of bradycardia is probable for both ziprasidone and aripiprazole. Symptomatic bradycardia with the use of other atypical antipsychotics has been reported in the literature. Little is known about the mechanisms that contribute to the antipsychotic-associated bradycardic response. CONCLUSIONS: Further studies are needed to better determine the relationship between antipsychotics and reflex bradycardia. Although bradycardia remains a relatively uncommon phenomenon seen with the use of these medications, the severity of this potential adverse effect warrants consideration when initiating antipsychotic therapy.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.