Enhanced renal clearance impacts levetiracetam concentrations in patients with traumatic brain injury with and without augmented renal clearance.

BACKGROUND: The purpose of this study was to examine the impact of ARC on levetiracetam concentrations during the first week following acute TBI. The hypothesis was levetiracetam concentrations are significantly lower in TBI patients with augmented renal clearance (ARC) compared to those with normal renal clearance. METHODS: This is a prospective cohort pharmacokinetic study of adults with moderate to severe TBI treated with levetiracetam during the first week after injury. Serial blood collections were performed daily for analysis of levetiracetam, cystatin C, and 12-hr creatinine clearance (CrCl) determinations. Patients were divided into two cohorts: with (CrCl ≥130 ml/min/1.73 m2) and without ARC. RESULTS: Twenty-two patients with moderate to severe TBI were included. The population consisted primarily of young male patients with severe TBI (mean age 40 years old, 68% male, median admission GCS 4). Each received levetiracetam 1000 mg IV every 12 h for the study period. ARC was present in 77.3% of patients, with significantly lower levetiracetam concentrations in ARC patients and below the conservative therapeutic range (< 6mcg/mL) for all study days. In patients without ARC, the serum concentrations were also below the expected range on all but two study days (Days 4 and 5). Four of the 22 (18.2%) patients exhibited seizure activity during the study period (two of these patients exhibited ARC). Cystatin C concentrations were significantly lower in patients with ARC, though the mean for all patients was within the typical normal range. CONCLUSIONS: ARC has a high prevalence in patients with moderate to severe TBI. Levetiracetam concentrations after standard dosing were low in all TBI patients, but significantly lower in patients with ARC. This study highlights the need to consider personalized drug dosing in TBI patients irrespective of the presence of ARC. CLINICAL TRIAL REGISTRATION: This study was registered at cliicaltrials.gov (NCT02437838) Registered on 08/05/2015, https://clinicaltrials.gov/ct2/show/NCT02437838 .

Intravenous Brivaracetam in the Management of Acute Seizures in the Hospital Setting: A Scoping Review.

BACKGROUND: Clinical considerations for drug treatment of acute seizures involve variables such as safety, tolerability, drug-drug interactions, dosage, route of administration, and alterations in pharmacokinetics because of critical illness. Therapy options that are easily and quickly administered without dilution, well tolerated, and effective are needed for the treatment of acute seizures. The objective of this review is to focus on the clinical considerations relating to the use of intravenous brivaracetam (IV BRV) for the treatment of acute seizures in the hospital, focusing on critically ill patients. METHODS: This was a scoping literature review of PubMed from inception to April 13, 2021, and search of the American Academy of Neurology (AAN) 2021 Annual Meeting website for English language publications/conference abstracts reporting the results of IV BRV use in hospitalized patients, particularly in the critical care setting. Outcomes of interest relating to the clinical pharmacology, safety, tolerability, efficacy, and effectiveness of IV BRV were reviewed and are discussed. RESULTS: Twelve studies were included for analysis. One study showed that plasma concentrations of IV BRV 15 min after the first dose were similar between patients receiving IV BRV as bolus or infusion. IV BRV was generally well tolerated in patients with acute seizures in the hospital setting, with a low incidence of individual TEAEs classified as behavioral disorders. IV BRV demonstrated efficacy and effectiveness and had a rapid onset, with clinical and electrophysiological improvement in seizures observed within minutes. Although outside of the approved label, findings from several studies suggest that IV BRV reduces seizures and is generally well tolerated in patients with status epilepticus. CONCLUSIONS: IV BRV shows effectiveness, and is generally well tolerated in the management of acute seizures in hospitalized patients where rapid administration is needed, representing a clinically relevant antiseizure medication for potential use in the critical care setting.

A review to characterise and map the growth mindset theory in health professions education.

INTRODUCTION: Growth mindset is a motivation theory proposed by Carol Dweck that posits our beliefs about intelligence, and the ability to change mindsets can have impacts on how we approach challenges, respond to criticism challenges and orient our goals. This study characterised articles on growth mindset theory in health professions education to: summarise the aspects of growth mindset being researched, describe the discussed benefits of growth mindset theory and outline strategies discussed that may promote a growth mindset. METHODS: A systematic review of the literature yielded 4927 articles-articles were reviewed and excluded if they were outside of health professions education and did not discuss Dweck's growth mindset theory. The final review yielded 14 research articles and 13 commentaries, which were characterised and analysed using content analysis. RESULTS: The included articles were published in 2016 and beyond; the articles represented a diverse context, participant type and approach. Most research studies measured participant mindsets and evaluated the correlation with other variables (eg grit, well-being, anxiety). Articles often highlighted benefits and strategies to promote a growth mindset at the learner, educator and organisation level. The most common learner benefits were to help them be more receptive to feedback as well as increased resiliency and perseverance, educator benefits focused on supporting collaborative relationships and safe learning environments. The most prevalent strategies discussed were teaching learners about growth mindset theory, shifting faculty feedback to emphasise effort and to prioritise feedback across the organisation. CONCLUSION: The growth mindset framework has been shown in other fields to help others manage educational challenges and enhance learning environments. Researchers are encouraged to explore how interventions such as teaching about and prioritising a growth mindset can support learners, health care professionals, educators and organisations.

The Neurocritical Care Society Gender Parity Analysis in Grants and Recognition Awards.

BACKGROUND: Several recent studies across the field of medicine have indicated gender disparity in the reception of prestigious awards and research grants, placing women in medicine at a distinct disadvantage. Gender disparity has been observed in neurology, critical care medicine and within various professional societies. In this study, we have examined the longitudinal trends of gender parity in awards and grants within the Neurocritical Care Society (NCS). METHODS: A retrospective analysis was conducted of all available data longitudinally from 2004, when NCS first granted awards through 2019. We used self-identified gender in the membership roster to record gender for each individual. For individuals without recorded gender, we used a previously validated double verification method using a systematic web-based search. We collected data on six awards distributed by the NCS and divided these awards into two main categories: (1) scientific category: (a) Christine Wijman Young Investigator Award; (b) Best Scientific Abstract Award; (c) Fellowship Grant; (d) INCLINE Grant; and (2) non-scientific category: (a) Travel Grant; and (b) Presidential Citation. Available data were analyzed to evaluate longitudinal trends in awards using descriptive statistics and simple or multiple linear regression analyses, as appropriate. RESULTS: A total of 445 awards were granted between the years 2004 and 2019. Thirty-six awards were in the scientific category, while 409 awards were in the non-scientific category. Only 8% of women received NCS awards in the scientific awards category, whereas 44% of women received an award in the non-scientific category. Most notable in the scientific category are the Best Scientific Abstract Award and the Fellowship Grant, in which no woman has ever received an award to date, compared to 18 men between both awards. In contrast, women are well represented in the non-scientific awards category with an average of 5% increase per year in the number of women awardees. CONCLUSIONS: Our data reveal gender disparity, mainly for scientific or research awards. Prompt evaluation of the cause and further actions to address gender disparity in NCS grants and recognition awards is needed to establish gender equity in this area.

A Longitudinal Study of Gender Parity Trends of General Membership and Leadership in the Neurocritical Care Society between 2002 and 2019.

BACKGROUND: Several studies in critical care and neurology demonstrate women under-representation in professional societies; representation trends within the Neurocritical Care Society (NCS) are unknown. We examined longitudinal gender parity trends in membership and leadership within NCS. METHODS: A retrospective study of NCS membership and leadership rosters was conducted. To determine gender, self-reported binary gender was extracted. For individuals without recorded gender, a systematic Web-based search to identify usage of gender-specific pronouns in publicly available biographies was performed. According to previously published methods, available photographs were utilized to record presumed gender identification in the absence of available pronoun descriptors. We analyzed available data longitudinally from 2002 to 2019 and performed descriptive statistical and linear regression analyses. RESULTS: In overall membership, the proportion of women members demonstrated an average 11% increase between 2005 and 2018 (95% confidence interval (CI) - 8.1 to 30.1, p = 0.08). The proportion of women Board of Directors (BOD) members increased significantly over time to 50% in 2019. There was an increase in women Officers from 0% in the first 3 years (2002-2004) to 40% in 2019, with two women Presidents out of 17 from 2002 to 2019. For available Executive Committee rosters, there was a statistically significant nearly 3% increase per year (95% CI 1.5-4; p = 0.0007) in the proportion of women members. Rosters for Committee members and chairpersons were also incomplete, but in an analysis of the available data, there was a statistically significant increase of 5% per year analyzed (95% CI 0.5-9.7; p = 0.04) in the proportion of women Committee members. We also found a statistically significant 4.3% increase per year analyzed (95% CI 2.4-6.1; p = 0.003) in the proportion of women Committee chairpersons. CONCLUSIONS: This is the first study of longitudinal gender parity trends within neurocritical care. We report that from 2002 to 2019, the NCS has undergone a significant increase in women representation in general membership, committee membership, and leadership positions.

Inactivated Four-Factor Prothrombin Complex Concentrate Dosing Practices for Reversal of Warfarin-Related Intracranial Hemorrhage.

BACKGROUND/OBJECTIVE: Inactivated four-factor prothrombin complex concentrate (I4F-PCC, Kcentra®) has become an important agent for the urgent or emergent reversal of bleeding associated with vitamin K antagonists such as warfarin. There is recognized inter-institutional variability with the use of I4F-PCC, especially as it relates to dosing practices. We sought to characterize variations in I4F-PCC dosing practices and their impact on patient outcomes and describe overall real-world clinical practice surrounding I4F-PCC utilization in the context of the management of warfarin-related intracranial hemorrhage (ICH). METHODS: This is a multicenter retrospective pragmatic registry study of adult patients admitted at a participating study site between January 1, 2014, and December 31, 2015, who received I4F-PCC for reversal of warfarin-related ICH. Practices around warfarin-related ICH reversal in context of I4F-PCC utilization are described, including repeat I4F-PCC dosing, adjunctive reversal agents, and dose rounding policies (i.e., rounding doses to nearest vial size vs preparing exact/unrounded doses). All research was approved by local human investigation committees at each institution. RESULTS: Seventeen institutions contributed data on 528 patients to this registry. These institutions were primarily urban centers (74%), located in the southeast USA (47%), with Level 1 Trauma designation (79%), and with Comprehensive Stroke Center designation (74%). Most patients included in the study had sustained a non-traumatic ICH (68%), had a median admission GCS of 14 (IQR 7-15), and were receiving warfarin for atrial fibrillation (57.4%). There was substantial time latency between baseline INR and I4F-PCC (median 2.4 h, IQR 1.4-4.5 h). Most patients received adjunctive reversal agents, including vitamin K (89.5%) and fresh frozen plasma (FFP) (31.9%). A smaller proportion (6.0%) of patients received repeat I4F-PCC dosing. The median ICU length of stay (LOS) was 3 days (IQR 2-7 days), median hospital LOS was 6 days (IQR 3-12 days), and overall mortality rate was 28.8%. For institutions rounding doses to the nearest vial size, the first post-I4F-PCC dose INR was statistically but not clinically significantly lower than for institutions without vial size dose rounding, with comparable degrees of INR reduction from baseline. No differences were observed between dose rounding cohorts in adverse effects, ICU or hospital LOS, modified Rankin score at discharge, or mortality rates. CONCLUSIONS: Most patients received single doses of I4F-PCC, with adjunctive reversal agents and rounding doses to vial size. The time difference from baseline INR to factor product administration is a potential opportunity for process improvement in the management of warfarin-related ICH.

Evaluation of the Accuracy of Standard Renal Function Equations in Critically Ill Patients with Subarachnoid Hemorrhage.

BACKGROUND: Obtaining an accurate estimation of renal function is germane to optimizing care in critically ill patients. However, there is no consensus on the most accurate renal function assessment to utilize in this patient population, particularly in aneurysmal subarachnoid hemorrhage (aSAH) patients. Thus, the objective of this observational study was to determine the comparability of renal function equations to body surface area (BSA)-adjusted 8-h creatinine clearance (CrCl) in aSAH patients. METHODS: A PubMed search investigated the applicability of various renal function equations in critically ill patient populations. A subset of these equations was compared to BSA-adjusted 8-h CrCl from a previous study with aSAH patients with no evidence of renal dysfunction (admission serum creatinine < 1.5 mg/dL) and no history of chronic kidney disease. Area-under-the-curve (AUC) calculations were completed using serial laboratory measurements to validate preliminary findings. RESULTS: A total of 14 renal function equations were identified with seven carried forward for further analysis based upon a priori criteria. Seven equations were excluded for various reasons, including lack of available clinical data, redundancy with other equations, and dissimilar patient populations to this study. When directly compared to the BSA-adjusted 8-h CrCl, only the Cockcroft-Gault and BSA-adjusted Cockcroft-Gault equations were not statistically significantly different (P = 0.0886 and P = 0.4805, respectively); all other equations were statistically significantly different (P < 0.0001). Additionally, only 52% and 44% of patients had average values within 20% of the BSA-adjusted 8-h CrCl using the Cockcroft-Gault and BSA-adjusted Cockcroft-Gault equations, respectively. Finally, the AUC calculations corroborated the preliminary findings with similar results in statistical testing for the Cockcroft-Gault and BSA-adjusted Cockcroft-Gault (P = 0.6300 and P = 0.1513, respectively). CONCLUSIONS: The Cockcroft-Gault equation may be the best renal function equation to assess in critically ill patients diagnosed with aSAH. However, accuracy and consistency in assessing renal function when compared to the BSA-adjusted 8-h CrCl were lacking. Thus, this study suggests the BSA-adjusted 8-h CrCl may be the most appropriate assessment of renal function in patients with aSAH.

Enhanced Renal Clearance in Patients With Hemorrhagic Stroke.

OBJECTIVES: To evaluate enhanced renal clearance over time in patients with aneurysmal subarachnoid hemorrhage or intracerebral hemorrhage via measured creatinine clearance and to compare measured creatinine clearance to creatinine clearance calculated by the Cockcroft-Gault equation and estimated glomerular filtration rate calculated by the Modification of Diet in Renal Diseases equation. DESIGN: Prospective, observational study. SETTING: Neurosciences ICU in a tertiary care academic medical center. PATIENTS: Study participants had an admission diagnosis of aneurysmal subarachnoid hemorrhage or intracerebral hemorrhage, an expected neurosciences ICU length of stay greater than 48 hours, no evidence of renal dysfunction (admission serum creatinine < 1.5 mg/dL), and no history of chronic kidney disease. INTERVENTIONS: Eight-hour urine collections to measure creatinine clearance were collected daily as the primary method of measuring renal function. Creatinine clearance was also calculated using the Cockcroft-Gault equation and estimated glomerular filtration rate was calculated using the Modification of Diet in Renal Disease equation. Enhanced renal clearance was defined as a measured creatinine clearance greater than the calculated creatinine clearance via Cockcroft-Gault and estimated glomerular filtration rate via Modification of Diet in Renal Disease. Augmented renal clearance was defined by a measured creatinine clearance greater than or equal to 130 mL/min/1.73 m. Relevant demographic, clinical, and outcome data were recorded. MEASUREMENTS AND MAIN RESULTS: Fifty aneurysmal subarachnoid hemorrhage patients and 30 intracerebral hemorrhage patients were enrolled, contributing 590 individual measurements. Patients with aneurysmal subarachnoid hemorrhage had a higher mean measured creatinine clearance compared with the mean calculated creatinine clearance based on the Cockcroft-Gault equation (147.9 ± 50.2 vs 109.1 ± 32.7 mL/min/1.73 m; p < 0.0001) and higher mean measured creatinine clearance compared with the mean calculated estimated glomerular filtration rate based on the Modification of Diet in Renal Disease equation (147.9 ± 50.2 vs 126.0 ± 41.9 mL/min/1.73 m; p = 0.04). Ninety-four percent of participants with aneurysmal subarachnoid hemorrhage experienced augmented renal clearance on at least 1 day. In patients with intracerebral hemorrhage, there was a higher mean measured creatinine clearance over the study period compared with the mean calculated creatinine clearance (119.5 ± 57.2 vs 77.8 ± 27.6 mL/min/1.73 m; p < 0.0001) and higher mean measured creatinine clearance compared with the mean calculated estimated glomerular filtration rate based on the Modification of Diet in Renal Disease equation (119.5 ± 57.2 vs 93.0.0 ± 32.8 mL/min/1.73 m; p = 0.02). Fifty percent of participants with intracerebral hemorrhage experienced augmented renal clearance on at least 1 day. CONCLUSIONS: A substantial group of patients with aneurysmal subarachnoid hemorrhage or intracerebral hemorrhage experienced enhanced renal clearance, which may be otherwise unknown to clinicians. Enhanced renal clearance may lead to increased renal solute elimination over what is expected, resulting in subtherapeutic renally eliminated drug concentrations. This may result in underexposure to critical medications, leading to treatment failure and other medical complications.

The Impact of Capping Creatinine Clearance on Achieving Therapeutic Vancomycin Concentrations in Neurocritically Ill Patients with Traumatic Brain Injury.

BACKGROUND: Traumatic brain injury (TBI) is associated with secondary complications, including infection, and patients with TBI often exhibit augmented renal clearance (ARC). This phenomenon has been associated with subtherapeutic levels of renally cleared drugs such as vancomycin, which is dosed based on body weight and creatinine clearance (CrCl). Many clinicians, however, cap CrCl at 120 mL/min/1.73 m2 when calculating vancomycin dosing regimens. We hypothesize that capping patient CrCl, as opposed to utilizing the non-capped CrCl, when determining vancomycin dosing schemes results in subtherapeutic serum trough concentrations in patients with TBI. METHODS: This was a retrospective study of adult patients with TBI admitted between April 2014 and December 2015 who received vancomycin. Population-based pharmacokinetic (PK) parameters using non-capped calculated CrCl and capped CrCl were compared with patient-specific PK parameters based on serum trough concentrations. RESULTS: Thirty-two patients with TBI were included in the study. ARC was suspected in 24 (75%) patients due to a median estimated CrCl at serum trough concentration of 167.3 (127.7-197.7) mL/min. The mean dosing regimen was 17.1 (13.2-19.2) mg/kg every 8 (8-8) h. There was no difference between the median measured trough concentration and predicted value using non-capped CrCl [10.4 (7.1-15.0) vs. 11.5 (7.8-13.7) mcg/mL; p = 0.7986]. The median measured trough concentration was significantly lower than the predicted trough concentration when calculated based on capping the CrCl at 120 mL/min/1.73 m2 [16.3 (15.3-22.0) vs. 11.5 (7.8-13.7) mcg/mL; p < 0.0001]. CONCLUSIONS: Patients with traumatic brain injury appeared to exhibit augmented renal clearance, leading to subtherapeutic vancomycin serum trough concentrations when doses were calculated using the traditional method of capping creatinine clearance at 120 mL/min/1.73 m2. Instead, utilizing patients' non-capped creatinine clearance when determining a vancomycin dosing regimen is more accurate and provides a better estimation of vancomycin pharmacokinetics and could be applied to other renally excreted medications.

Common Data Elements for Unruptured Intracranial Aneurysm and Subarachnoid Hemorrhage Clinical Research: Recommendations from the Working Group on Long-Term Therapies.

OBJECTIVES: The goal for the long-term therapies (LTT) working group (WG) of the Unruptured Intracranial Aneurysm (UIA) and Subarachnoid Hemorrhage (SAH) common data elements (CDEs) was to develop a comprehensive set of CDEs, data definitions, case report forms, and guidelines for use in UIA and SAH LTT clinical research, as part of a new joint effort between the National Institute of Neurological Disorders and Stroke (NINDS) and the National Library of Medicine of the US National Institutes of Health. These UIA and SAH CDEs will join other neurological disease-specific CDEs already developed and available for use by research investigators. METHODS: The eight LTT WG members comprised international UIA, and SAH experts reviewed existing NINDS CDEs and instruments, created new elements when needed, and provided recommendations for future LTT clinical research. The recommendations were compiled, internally reviewed by the all UIA and SAH WGs and steering committee members. The NINDS CDE team also reviewed the final version before posting the SAH Version 1.0 CDE recommendations on the NINDS CDE website. RESULTS: The NINDS UIA and SAH LTT CDEs and supporting documents are publicly available on the NINDS CDE ( https://www.commondataelements.ninds.nih.gov/#page=Default ) and NIH Repository ( https://cde.nlm.nih.gov/home ) websites. The subcommittee members discussed and reviewed various parameters, outcomes, and endpoints in UIA and SAH LTT studies. The following meetings with WG members, the LTT WG's recommendations are incorporated into the disease/injury-related events, assessments and examinations, and treatment/intervention data domains. CONCLUSIONS: Noting gaps in the literature regarding medication and rehabilitation parameters in UIA and SAH clinical studies, the current CDE recommendations aim to arouse interest to explore the impact of medication and rehabilitation treatments and therapies and encourage the convergence of LTT clinical study parameters to develop a harmonized standard.

Correction to: Influence of Single-Dose Antibiotic Prophylaxis for Early-Onset Pneumonia in High-Risk Intubated Patients.

Due to an error introduced during the production process, J. Dedrick Jordan's name was improperly tagged in the original publication of this article. It is tagged correctly here.

Influence of Single-Dose Antibiotic Prophylaxis for Early-Onset Pneumonia in High-Risk Intubated Patients.

BACKGROUND: Early-onset pneumonia (EOP) after endotracheal intubation is common among critically ill patients with a neurologic injury and is associated with worse clinical outcomes. METHODS: This retrospective cohort study observed outcomes pre- and post-implementation of an EOP prophylaxis protocol which involved the administration of a single dose of ceftriaxone 2 g around the time of intubation. The study included patients ≥ 18 years who were admitted to the University of North Carolina Medical Center (UNCMC) neuroscience intensive care unit (NSICU) between April 1, 2014, and October 26, 2016, and intubated for ≥ 72 h. RESULTS: Among the 172 patients included, use of an EOP prophylaxis protocol resulted in a significant reduction in the rate of microbiologically confirmed EOP compared to those without prophylaxis (7.4 vs 19.8%, p = 0.026). However, EOP prophylaxis did not decrease the combined incidence of microbiologically confirmed or clinically suspected EOP (32.2 vs 37.4%, p = 0.523). No difference in the rate of late-onset pneumonia (34.6 vs 26.4%, p = 0.25) or virulent organism growth (19.8 vs 14.3%, p = 0.416) was observed. No difference was observed in the duration of intubation, duration of intensive care unit (ICU) stay, duration of hospitalization, or ICU antibiotic days within 30 days of intubation. In hospital mortality was found to be higher in those who received EOP prophylaxis compared to those who did not receive prophylaxis (45.7 vs 29.7%, p = 0.04). CONCLUSIONS: The administration of a single antibiotic dose following intubation may reduce the incidence of microbiologically confirmed EOP in patients with neurologic injury who are intubated ≥ 72 h. A prophylaxis strategy does not appear to increase the rate of virulent organism growth or the rate of late-onset pneumonia. However, this practice is not associated with a decrease in days of antibiotic use in the ICU or any clinical outcomes benefit.

Optimizing Medication Outcomes in Neurocritical Care: Focus on Clinical Pharmacology.

Drug dosing in neurocritically ill patients presents enormous challenges for clinicians due to the complex pathophysiological alterations. These alterations are dynamic both between and within patients. Unpredictable exposure from standard dosing regimens, which were extrapolated to intensive care unit patients from healthy volunteer studies, may influence medication outcomes. Knowledge of potential alterations in pharmacokinetics/pharmacodynamics in these patients could be applied to maximize the clinical response and minimize adverse effects. Recognizing potential confounding clinical and treatment factors affecting drug response is an important step, but it is not enough. Overcoming absorption and distribution challenges by using specialized formulations and delivery systems is an area of active research. Improved methods for measuring drug concentrations in clinical settings across different matrices are also needed. Even with these advances, defining endogenous mediators signaling drug-target activation is necessary. Identifying biomarkers in disease and changes when a drug has reached its target will be pivotal. This information will improve our understanding of the pharmacogenomic and pharmacokinetic variables affecting pharmacodynamic endpoints across a spectrum of neurologic diseases.

Vancomycin Pharmacokinetic Parameters in Patients with Hemorrhagic Stroke.

BACKGROUND: Infections are a common medical complication in hemorrhagic stroke patients, with vancomycin commonly used as empiric therapy. The purpose of this study was to evaluate the pharmacokinetic parameters of vancomycin in hemorrhagic stroke patients. METHODS: This was a retrospective study of adult patients with aneurysmal subarachnoid hemorrhage (aSAH) or intracerebral hemorrhage (ICH) admitted between May 2010 and February 2015 who received vancomycin. Predicted pharmacokinetic parameters based on population data were compared with calculated pharmacokinetic parameters based on serum trough concentrations. RESULTS: Eighty aSAH patients and 66 ICH patients met inclusion criteria. In the aSAH group, the mean dosing regimen was 17.6 ± 4 mg/kg every 12 (8-12) h. The mean measured trough concentration was lower than the predicted trough concentration (9.9 ± 4.1 vs. 19 ± 8.7 µg/mL; p < 0.001). The mean calculated elimination rate constant was higher than the predicted value (0.135 ± 0.04 vs. 0.092 ± 0.03 h(-1); p < 0.001), and the mean calculated half-life was lower than predicted (5.7 ± 1.8 vs. 8.3 ± 2.9 h; p < 0.001). In the ICH group, the mean dosing regimen was 15.9 ± 4.3 mg/kg every 12 (8-12) h. Similarly, the mean measured trough concentration was lower than the predicted trough concentration (10.7 ± 4.6 vs. 17.5 ± 8.5 µg/mL; p < 0.001). The mean calculated elimination rate constant was higher than the predicted value (0.106 ± 0.03 vs. 0.079 ± 0.02 h(-1); p < 0.001), and the mean calculated half-life was lower than predicted (7.2 ± 2.3 vs. 9.6 ± 3.2 h; p < 0.001). CONCLUSIONS: Patients with hemorrhagic stroke exhibited pharmacokinetic alterations favoring increased elimination of vancomycin when compared to predicted pharmacokinetic parameters based on population data. This may result in underexposure to vancomycin, leading to treatment failure and other medical complications.

Acute or chronic use of lacosamide does not alter its distribution between serum and cerebrospinal fluid.

OBJECTIVE: The site of action for antiepileptic drugs (AEDs) is within the brain; however, cerebrospinal fluid (CSF) concentration is highly variable. Lacosamide (LCM) is approved by the U.S. Food and Drug Administration (FDA) for treatment of partial-onset seizures in adults, and has linear pharmacokinetics in serum. Penetration across the blood-brain barrier (BBB) is unknown. This study aims to provide additional insights into the pharmacokinetics of LCM. METHODS: Thirty adults undergoing craniotomy for treatment of intractable epilepsy or brain tumor were recruited and were either taking LCM long term (group 1, n = 15), or were LCM naive, receiving LCM as prophylaxis for surgery (group 2, n = 15). All patients received one intravenous (IV) dose (15 min infusion) immediately prior to craniotomy. CSF and arterial blood were collected simultaneously following craniotomy. LCM concentrations were measured in serum and CSF. RESULTS: LCM concentration differences between groups 1 and 2 for both CSF and serum were statistically significant (p ≤ 0.0005), but there was no statistically significant difference in CSF/serum ratios (group 1 = 0.726 ± 0.231; group 2 = 0.556 ±0.241; p = 0.0585). LCM concentration in serum correlated positively with CSF concentration in group 1 (Pearson r = 0.8527, p < 0.0001). The time interval between the end of dose delivery and sample collection correlated positively with the CSF/serum ratio for the drug-naive group (Pearson r = 0.6525; p = 0.0084). Treatment with other AEDs did not affect LCM distribution between serum and CSF. SIGNIFICANCE: Although chronic dosing resulted in higher LCM concentrations in serum and CSF compared to drug-naive patients, the CSF/serum ratio was not affected by LCM pretreatment. These data suggest that LCM serum concentration may reliably predict CSF concentration.

Vancomycin pharmacokinetic parameters in patients with acute brain injury undergoing controlled normothermia, therapeutic hypothermia, or pentobarbital infusion.

BACKGROUND: Therapeutic strategies that cause an alteration in patient temperature, such as controlled normothermia (CN), therapeutic hypothermia (TH), and pentobarbital infusion (PI), are often used to manage complications caused by acute brain injury. The purpose of this study was to evaluate pharmacokinetic (PK) parameters of vancomycin in patients with acute brain injury undergoing temperature modulation. METHODS: This was a retrospective cohort study of adult patients with acute brain injury admitted between May 2010 and March 2014 who underwent CN, TH, or PI and received vancomycin. Predicted PK parameters based on population data were compared with calculated PK parameters based on serum concentrations. RESULTS: Seventeen CN patients and 10 TH/PI patients met inclusion criteria. Traumatic brain injury and aneurysmal subarachnoid hemorrhage accounted for the majority of admitting diagnoses. In the CN group, the median dose was 16.7 (15.5-18.4) mg/kg. The median calculated elimination rate constant [0.155 (0.108-0.17) vs. 0.103 (0.08-0.142) hr(-1); p = 0.04] was significantly higher than the predicted value. The median measured trough concentration [8.9 (7.7-11.1) vs. 17.1 (10.8-22.3) υg/mL; p = 0.004] was significantly lower than predicted. In the TH/PI group, the median dose was 15.4 (14.7-17.2) mg/kg. No significant differences were found between the median calculated and predicted elimination rate constant [0.107 (0.097-0.109) vs. 0.112 (0.102-0.127) hr(-1); p = 0.41] and median measured and predicted trough concentration [14.2 (12.7-17.1) vs. 13.1 (11-17.8) υg/mL; p = 0.71]. CONCLUSION: Patients who underwent TH/PI did not exhibit PK alterations when compared to predicted PK parameters based on population data, while patients who underwent CN experienced PK alterations favoring an increased elimination of vancomycin.

Evidence-based guidelines for the management of large hemispheric infarction : a statement for health care professionals from the Neurocritical Care Society and the German Society for Neuro-intensive Care and Emergency Medicine.

Large hemispheric infarction (LHI), also known as malignant middle cerebral infarction, is a devastating disease associated with significant disability and mortality. Clinicians and family members are often faced with a paucity of high quality clinical data as they attempt to determine the most appropriate course of treatment for patients with LHI, and current stroke guidelines do not provide a detailed approach regarding the day-to-day management of these complicated patients. To address this need, the Neurocritical Care Society organized an international multidisciplinary consensus conference on the critical care management of LHI. Experts from neurocritical care, neurosurgery, neurology, interventional neuroradiology, and neuroanesthesiology from Europe and North America were recruited based on their publications and expertise. The panel devised a series of clinical questions related to LHI, and assessed the quality of data related to these questions using the Grading of Recommendation Assessment, Development and Evaluation guideline system. They then developed recommendations (denoted as strong or weak) based on the quality of the evidence, as well as the balance of benefits and harms of the studied interventions, the values and preferences of patients, and resource considerations.

AACP's Strategic Commitment to Improving Pharmacy Education: Past, Present, and Future.

Since its founding in 1900, the American Association of Colleges of Pharmacy (AACP) has been focused on quality pharmacy education. As the Association and its institutional and individual members now consider contemporary issues in education, such as competency-based education, it is important to continue their collective work in the context of AACP's enduring mission: to advance pharmacy education, research, scholarship, practice, and service, in partnership with members and stakeholders, to improve health for all. While language, labels, and strategies evolve over time and across significant changes in social, economic, political, and health care environments, AACP's commitment to quality in education has been and must continue to be unwavering. Constraints and challenges perceived in the short term should not deter deliberate and strategic quality improvement efforts over time and in the longer term. AACP's 2021-2024 Strategic Plan, entitled Preparing Pharmacists and the Academy to Thrive in Challenging Times, acknowledges the need to prepare pharmacists for seemingly constant change in the health care environment.

Competency-Based Education: The Need to Debunk Misconceptions and Develop a Common Language.

Competency-based education (CBE) dates back to the early 1900s. A renewed interest in CBE in health professions education has been sparked by the recommendations that emerged from the 2017 Josiah Macy Jr Foundation conference on CBE. These recommendations urge changes in structure and pedagogy to address gaps between societal needs, health care practice, and health professions education. Despite widespread interest, there is significant variability in what constitutes CBE. This variability has challenged the development of an evidence base in the literature and has led to widespread misconceptions regarding CBE. Implementation science principles outline the need to develop a common language to inform effective and sustained implementation of an innovation. By misusing or overusing similar words and using different concepts interchangeably without first developing a common, widely understood language around CBE, we cannot expect that CBE will be among the tools successful in closing gaps between health care practice and education.

Use of a clinical reasoning scaffolding document improves student performance.

OBJECTIVE: Clinical reasoning is an essential skill set for practicing pharmacists to possess. Given its complex nature, optimal pedagogies for teaching clinical reasoning are largely unknown. The use of scaffolding to expand a student's zone of proximal development and improve clinical reasoning performance was assessed in this study. METHODS: This prospective, observational cohort study of second professional year (P2) students compared performance of those who were exposed to a clinical reasoning scaffolding tool (CRST) to historic control P2 students (No CRST) on FARMR notes in alignment with the Pharmacists' Patient Care Process. Student performance was assessed using an entrustment-like scale for each of 5 sections (Findings, Assessment and goals, Recommendations, Monitoring, and Rationale) of the FARMR to link classroom and experiential education settings. RESULTS: In total, 141 CRST students from 28 groups were compared to 77 No CRST students from 13 groups. CRST students performed significantly higher in Assessment and goals of therapy, Recommendations, Monitoring, Rationale sections but no difference in Findings. CONCLUSIONS: Scaffolding has been utilized successfully in other health professions education. This study provides evidence of it successfully improving student pharmacist clinical reasoning skills, an essential ability for successful pharmacy practitioners.