Hadean silicate differentiation preserved by anomalous 142Nd/144Nd ratios in the Réunion hotspot source.

Active volcanic hotspots can tap into domains in Earth's deep interior that were formed more than two billion years ago. High-precision data on variability in tungsten isotopes have shown that some of these domains resulted from differentiation events that occurred within the first fifty million years of Earth history. However, it has not proved easy to resolve analogous variability in neodymium isotope compositions that would track regions of Earth's interior whose composition was established by events occurring within roughly the first five hundred million years of Earth history. Here we report 142Nd/144Nd ratios for Réunion Island igneous rocks, some of which are resolvably either higher or lower than the ratios in modern upper-mantle domains. We also find that Réunion 142Nd/144Nd ratios correlate with helium-isotope ratios (3He/4He), suggesting parallel behaviour of these isotopic systems during very early silicate differentiation, perhaps as early as 4.39 billion years ago. The range of 142Nd/144Nd ratios in Réunion basalts is inconsistent with a single-stage differentiation process, and instead requires mixing of a conjugate melt and residue formed in at least one melting event during the Hadean eon, 4.56 billion to 4 billion years ago. Efficient post-Hadean mixing nearly erased the ancient, anomalous 142Nd/144Nd signatures, and produced the relatively homogeneous 143Nd/144Nd composition that is characteristic of Réunion basalts. Our results show that Réunion magmas tap into a particularly ancient, primitive source compared with other volcanic hotspots, offering insight into the formation and preservation of ancient heterogeneities in Earth's interior.

Prevalence and Categorization of Drug-Related Problems in the Emergency Department.

BACKGROUND: Drug-related problems (DRPs) are common among patients seen in the emergency department (ED), but the true incidence is not clear. OBJECTIVES: The primary objective of this study was to determine the prevalence of DRPs among patients seen in a U.S. ED. The secondary objective was to categorize these DRPs by problem type and by medication class. METHODS: This was a prospective observational cohort study of a random sample of ED patients between December 2011 and March 2013. ED pharmacists screened randomly selected patients for the presence of a DRP contributing to the ED visit. Four independent auditors evaluated the results to achieve consensus for the presence or absence of DRPs and categorization of the DRPs. RESULTS: Among 1039 patients screened for DRPs, 308 (29.6%) were found to have at least 1 DRP contributing to the ED visit. Among a total of 443 DRPs, the most commonly identified categories were adverse drug reaction (n = 193 [43.6%]), ineffective medication (n = 69 [15.6%]), and subtherapeutic dosage (n = 68 [15.3%]). The most commonly implicated drug classes were cardiovascular medications (n = 113 [26.5%]), anti-infective medications (n = 52 [12.2%]), and analgesic medications (n = 58 [13.6%]). CONCLUSIONS: A substantial proportion of ED visits are associated in part or in total with DRPs. Adverse drug reactions and cardiovascular medications are the most common category and medication class implicated, respectively.

Ketamine for Primary Analgosedation in Critically Ill Surgery and Trauma Patients Requiring Mechanical Ventilation.

OBJECTIVES: Evaluate effectiveness and safety outcomes associated with the use of ketamine for primary analgosedation in the surgical/trauma ICU setting. DESIGN: Retrospective cohort study. SETTING: Academic medical center in Minnesota. PATIENTS: Patients admitted to the surgical ICU between 2015 and 2019 requiring mechanical ventilation and meeting one of three definitions for ketamine primary analgosedation were included: 1) no concomitant opioid infusion, 2) ketamine monotherapy for greater than or equal to 6 hours with subsequent opioid infusion, or 3) ketamine initiated concomitantly or within 4 hours of opioid and total opioid duration less than 4 hours. INTERVENTIONS: None. MEASUREMENTS: Use of ketamine, analgesics, and sedatives were evaluated. Pain, sedation, and delirium assessments immediately before and during ketamine infusion were collected and compared with reported goals. Concomitant analgesics, sedatives, and psychotropics were recorded. Reported failures due to ineffectiveness and toxicity were collected. MAIN RESULTS: Of 164 included patients, 88% never received a concomitant opioid infusion (primary analgosedation definition 1), 12% met alternative criteria for primary analgosedation (definitions 2 and 3). A majority, 68%, were surgical admissions and mean Acute Physiology and Chronic Health Evaluation III score was 90 (± 30). Median mechanical ventilation duration was 2.5 days (1.1-4.5) and ICU length of stay of 4.9 days (3-8). The median ketamine infusion dose and duration were 0.18 mg/kg/hr (0.1-0.3) and 30 hours (15.1-51.8). Concomitant infusions of propofol and dexmedetomidine were administered in 49% and 29% of patients, respectively. During ketamine infusion, the median percent of total pain scores at goal was 62% (33-96%), while 64% (37-91%) of Richmond Agitation Sedation Scale scores were at goal, and 47% of patients were Confusion Assessment Method-ICU positive during the ketamine infusion. Hallucinations were documented in 14% of patients and ketamine failure occurred in 11% of patients. CONCLUSIONS: Ketamine may be an effective primary analgosedation option in intubated surgical ICU patients, but prospective randomized studies are needed to evaluate this strategy.

Continuous Renal Replacement Therapy and Mortality in Critically Ill Obese Adults.

IMPORTANCE: The outcomes of critically ill adults with obesity on continuous renal replacement therapy (CRRT) are poorly characterized. The impact of CRRT dose on these outcomes is uncertain. OBJECTIVES: This study aimed to determine if obesity conferred a survival advantage for critically ill adults with acute kidney injury (AKI) on CRRT. Secondarily, we evaluated whether the dose of CRRT predicted mortality in this population. DESIGN SETTING AND PARTICIPANTS: A retrospective, observational cohort study performed at an academic medical center in Minnesota. The study population included critically ill adults with AKI managed with CRRT. MAIN OUTCOMES AND MEASURES: The primary outcome of 30-day mortality was compared between obese (body mass index [BMI] ≥ 30 kg/m2) and nonobese (BMI < 30 kg/m2) patients. Multivariable regression assessed was used to assess CRRT dose as a predictor of outcomes. An analysis included dose indexed according to actual body weight (ABW), adjusted body weight (AdjBW), or ideal body weight (IBW). RESULTS: Among 1033 included patients, the median (interquartile range) BMI was 26 kg/m2 (23-28 kg/m2) in the nonobese group and 36 kg/m2 (32-41 kg/m2) in the obese group. Mortality was similar between groups at 30 days (54% vs. 48%; p = 0.06) but lower in the obese group at 90 days (62% vs. 55%; p = 0.02). CRRT dose predicted an increase in mortality when indexed according to ABW or AdjBW (hazard ratio [HR], 1.2-1.16) but not IBW (HR, 1.04). CONCLUSIONS AND RELEVANCE: In critically ill adults with AKI requiring CRRT, short-term mortality appeared lower in obese patients compared with nonobese patients. Among weight calculations, IBW appears to be preferred to promote safe CRRT dosing in obese patients.

The effect of plasma exchange on serum levels of lacosamide: A case report.

PURPOSE: We describe the case of a 22-year-old male who developed thyroid storm necessitating therapeutic plasma exchange (TPE). The patient's past medical history was complicated by epilepsy, for which he took lacosamide. Little evidence was available to guide lacosamide dosing during TPE. Because of an exacerbation of the patient's underlying epilepsy in the context of the thyroid storm, we conducted therapeutic medication monitoring of lacosamide concentrations to guide management. SUMMARY: We arranged for measurement of the lacosamide concentration immediately before TPE (5.1 µg/mL) and 2.5 hours after the initial measurement (3.4 µg/mL) to determine the amount of lacosamide removed by TPE. Utilizing population pharmacokinetic parameters, we calculated the expected concentration and compared this to the measured concentration. The difference between these values was used to determine the percentage removed via TPE compared to the expected post-TPE concentration. We found that one TPE session removed an additional 20% of serum lacosamide. CONCLUSION: TPE appeared to remove an additional 20% of lacosamide when compared to the expected post-TPE concentration.

Use of Remdesivir in Myasthenia gravis and COVID-19.

Myasthenia gravis and the associated pharmacologic management options could place patients at higher risk of contracting severe acute respiratory syndrome coronavirus 2 and exhibiting more severe manifestations of the novel coronavirus disease 2019 (COVID-19). Multiple agents have been studied for the management of the COVID-19, including remdesivir. To date, no published reports have evaluated the utilization of the antiviral remdesivir in patients with myasthenia gravis. We describe the first reported clinical course of three patients with myasthenia gravis who safely received remdesivir in combination with dexamethasone for the management of COVID-19.

Effect of plasma exchange on antifactor Xa activity of enoxaparin and serum levetiracetam levels.

PURPOSE: The effect of therapeutic plasma exchange (TPE) on antifactor Xa activity in a patient treated with enoxaparin and levetiracetam is reported. SUMMARY: A 52-year-old woman was treated with levetiracetam and prophylactic enoxaparin while receiving TPE to manage respiratory failure due to anti-MDA5 antibody-associated interstitial lung disease (ILD) with dermatomyositis. Due to a scant amount of evidence regarding the management of these medications in TPE, therapeutic monitoring principles were used to assess the effect TPE had on these medications. A pre-TPE antifactor Xa activity level and levetiracetam serum assay, a post-TPE antifactor Xa activity level and levetiracetam serum assay, levetiracetam serum assays at 1 and 6 hours after the patient received her next dose, and a levetiracetam assay of the waste plasma from the TPE were collected for therapeutic drug monitoring and pharmacokinetic calculations. Utilizing standard population pharmacokinetic data, the expected antifactor Xa activity without TPE was 0.14 IU/mL. This concentration was significantly higher than the undetectable concentration (<0.1 IU/mL) that was drawn immediately after TPE, suggesting significant removal of antifactor Xa activity. The measured levetiracetam level did not significantly differ from the expected post-TPE levetiracetam level that was calculated using patient-specific pharmacokinetic data. CONCLUSION: In a patient receiving TPE to manage anti-MDA5 antibody ILD associated with dermatomyositis and a prior seizure, TPE significantly altered enoxaparin antifactor Xa activity as evidenced by the undetectable antifactor Xa activity level drawn after TPE. Alternatively, TPE had a minimal effect on the clearance of levetiracetam as evidenced by the post-TPE level and fraction elimination of only 5% of total body stores.

Impact of Serum Cystatin C-Based Glomerular Filtration Rate Estimates on Drug Dose Selection in Hospitalized Patients.

STUDY OBJECTIVE: Serum creatinine (Scr ) concentration is used to calculate estimated glomerular filtration rate (eGFR) for medication dosing. Serum cystatin C (CysC) concentration has been proposed as an adjunct or alternative to Scr . This study sought to evaluate the possible impact of using CysC in eGFR equations on drug dose recommendations in hospitalized patients with infections. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Large academic tertiary care medical center. PATIENTS: A total of 308 adults with suspected or documented infections and stable kidney function who were hospitalized between 2012 and 2015. MEASUREMENTS AND MAIN RESULTS: Standardized Scr and CysC measured at the time of antibiotic dosing were used to estimate GFR from the three Chronic Kidney Disease Epidemiology Collaborative (CKD-EPI) equations using Scr (eGFRCr ), CysC(eGFRCysC ), or a combination of Scr and CysC (eGFRCr-CysC ), and these values were compared with estimated creatinine clearance (eClcr ) from the Cockcroft-Gault equation (standard of care for drug dosage adjustments). The eGFRs were categorized into five common dosage adjustment strata (lower than 20, 20-49, 50-79, 80-130, and higher than 130 ml/min), and agreement between equations was tested with the weighted κ statistic. Recommended drug doses varied considerably between the eClcr and the CKD-EPI equations (weighted κ [95% confidence interval]: eGFRCr 0.73 [0.68-0.79], eGFRCysC 0.42 [0.35-0.5], eGFRCr-CysC 0.65 [0.6-0.71]). If eGFRCr, eGFRCysC , or eGFRCr-CysC were used instead of eClcr to dose drugs, 11%, 12%, and 8% of doses, respectively, would be higher, and 12%, 38%, and 24% of doses, respectively, would be lower. CONCLUSION: Significant discordance in drug doses was observed when the CKD-EPI equations were used in place of eClcr . When CysC was included in eGFR equations, recommended doses were often lower. Further study is needed to develop and test drug-specific dosing guidelines that incorporate alternate renal biomarkers and/or more contemporary eGFR equations.

Does Obesity Predispose Medical Intensive Care Unit Patients to Venous Thromboembolism despite Prophylaxis? A Retrospective Chart Review.

Background. Obesity is a significant issue in the critically ill population. There is little evidence directing the dosing of venous thromboembolism (VTE) prophylaxis within this population. We aimed to determine whether obesity predisposes medical intensive care unit patients to venous thromboembolism despite standard chemoprophylaxis with 5000 international units of subcutaneous heparin three times daily. Results. We found a 60% increased risk of venous thromboembolism in the body mass index (BMI) ≥ 30 kg/m2 group compared to the BMI < 30 kg/m2 group; however, this difference did not reach statistical significance. After further utilizing our risk model, neither obesity nor mechanical ventilation reached statistical significance; however, vasopressor administration was associated with a threefold risk. Conclusions. We can conclude that obesity did increase the rate of VTE, but not to a statistically significant level in this single center medical intensive care unit population.