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Study Objective: Enoxaparin is standard of care for venous thromboembolism (VTE) prophylaxis in adult trauma patients, but fixed-dose protocols are suboptimal. Dosing based on body mass index (BMI) or total body weight (TBW) improves target prophylactic anti-Xa level attainment and reduces VTE rates. A novel strategy using estimated blood volume (EBV) may be more effective based on results of a single-center study. This study compared BMI-, TBW-, EBV-based, and hybrid enoxaparin dosing strategies at achieving target prophylactic anti-Factor Xa (anti-Xa) levels in trauma patients., Design: Multicenter, retrospective review., Data Source: Electronic health records from participating institutions., Patients: Adult trauma patients who received enoxaparin twice daily for VTE prophylaxis and had at least one appropriately timed anti-Xa level (collected 3 to 6 hours after the previous dose after three consecutive doses) from January 2017 through December 2020. Patients were excluded if the hospital-specific dosing protocol was not followed or if they had thermal burns with > 20% body surface area involvement., Intervention: Dosing strategy used to determine initial prophylactic dose of enoxaparin., Measurements: The primary end point was percentage of patients with peak anti-Xa levels within the target prophylactic range (0.2-0.4 units/mL)., Main Results: Nine hospitals enrolled 742 unique patients. The most common dosing strategy was based on BMI (43.0%), followed by EBV (29.0%). Patients dosed using EBV had the highest percentage of target anti-Xa levels (72.1%). Multiple logistic regression demonstrated EBV-based dosing was significantly more likely to yield anti-Xa levels at or above target compared to BMI-based dosing (adjusted odds ratio (aOR) 3.59, 95% confidence interval (CI) 2.29-5.62, p < 0.001). EBV-based dosing was also more likely than hybrid dosing to yield an anti-Xa level at or above target (aOR 2.30, 95% CI 1.33-3.98, p = 0.003). Other pairwise comparisons between dosing strategy groups were nonsignificant., Conclusions: An EBV-based dosing strategy was associated with higher odds of achieving anti-Xa level within target range for enoxaparin VTE prophylaxis compared to BMI-based dosing and may be a preferred method for VTE prophylaxis in adult trauma patients., (© 2023 Pharmacotherapy Publications, Inc.)

Purpose: Fixed-dose and body mass index (BMI)-based enoxaparin regimens provide inadequate venous thromboembolism (VTE) prophylaxis for many trauma patients. The purpose of this study was to evaluate the effectiveness of a novel blood volume (BV)-based enoxaparin guideline vs a historical BMI-based guideline for VTE prophylaxis in trauma patients., Methods: This was a retrospective pre/post study completed at a large academic level 1 trauma center. All adult trauma patients admitted from October through December 2019 and August through October 2020 who received prophylactic enoxaparin per guideline were included. The BV dosing was as follows: patients with a BV of 3 to 4.9 L received enoxaparin 30 mg every 12 hours, those with a BV of 5 to 6.9 L received 40 mg every 12 hours, and those with a BV of ≥7 L received 60 mg every 12 hours. The primary outcome was the percentage of patients who attained a target anti-factor Xa (anti-Xa) postdosing level at the first steady-state assessment (0.2 to 0.5 IU/mL)., Results: A total of 241 patients (99 for the BMI group and 142 for the BV group) were included. The study groups had a median age of 38 vs 42 years, a mean BMI of 27.4 vs 27.7 kg/m2, and a mean BV of 5.1 vs 5.1 L, respectively. A total of 63 patients (62.6%) in the BMI group attained target anti-Xa levels compared to 115 patients (81%) in the BV group (P = 0.008). In multivariate regression, the BV-based guideline was the only variable associated with attainment of target anti-Xa levels (adjusted odds ratio, 2.02; P = 0.01). Clinically relevant bleeding and VTE rates were similar between the groups., Conclusion: Dosing prophylactic enoxaparin using a BV-based dosing guideline significantly increased attainment of target anti-Xa levels., (© American Society of Health-System Pharmacists 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Enoxaparin is administered for venous thromboembolic (VTE) prophylaxis in bariatric surgery patients. There is concern whether body mass index (BMI)-based enoxaparin dosing consistently achieves prophylactic targets in patients with severe obesity., Methods: This retrospective study included patients who underwent bariatric surgery at an academic medical center from Jan 2015-May 2021 and had an anti-Xa level drawn 2.5-6 h after ≥3 doses of BMI-based prophylactic enoxaparin. The primary outcome was the percentage of patients who achieved a target anti-Xa level. Secondary outcomes were prevalence of venous thromboembolic and bleeding events within 30 d post-operatively., Results: Overall, 137 patients were included. Mean BMI was 59.1 ± 10.4 kg/m 2 , mean age was 43.9 ± 13.3 y and 110 patients (80.3%) were female. Target anti-Xa levels were achieved in 116 patients (84.7%); 14 (10.2%) were above target and 7 (5.1%) were below target. Patients with above target anti-Xa levels were significantly shorter in height than those within target range (167.1 versus 159.8 cm, P = 0.003). Five patients (3.6%) had a bleeding event; no thromboembolisms occurred. Anti-Xa levels correlated more strongly with enoxaparin dose per unit estimated blood volume (EBV) than dose per unit BMI (Rho = 0.54 versus Rho = 0.33)., Conclusions: Target range anti-Xa levels were achieved in 85% of patients using BMI-based enoxaparin dosing. Patients with above target anti-Xa levels were significantly shorter by nearly 3 inches, suggesting an increased risk of overdosing enoxaparin in shorter, obese patients. An EBV-based dosing regimen may better account for patient height and is supported by a greater correlation with anti-Xa levels with dosing based on EBV than BMI., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to evaluate the effectiveness of a body mass index (BMI)-based enoxaparin prophylaxis dosing protocol at achieving target anti-factor Xa (anti-Xa) concentrations in the trauma population., Methods: This retrospective chart review evaluated anti-Xa concentrations in adult trauma patients who received prophylactic enoxaparin over a three-month period. The primary outcome was the percentage of patients that achieved target anti-Xa concentrations after ≥3 doses of enoxaparin. Secondary outcomes included correlations of anti-Xa concentrations with enoxaparin dose per BMI, total body weight (TBW), and estimated blood volume (EBV). The prevalence of clinically relevant bleeding and venous thromboembolism was also recorded. Multivariable logistic regression was used to identify associated variables for target anti-Xa concentration attainment., Results: Ninety-nine consecutive patients were included in the study. Included patients were predominately male (69.7%) and Black (50.5%) with a mean age of 44.1 years. Target anti-Xa concentrations were achieved in 62.6% of patients. Anti-Xa concentrations were moderately correlated with enoxaparin dose per EBV (ρ = 0.57), followed by dose per TBW (ρ = 0.46), and dose per BMI (ρ = 0.20). Multivariable logistic regression demonstrated that categorization of enoxaparin dose per EBV and per TBW were the only statistically significant predictors of reaching target anti-Xa concentrations (p = <0.001)., Conclusions: In adult trauma patients, the rate of achieving target anti-Xa concentrations remains suboptimal and provides room for further improvement. Enoxaparin dose per EBV was more closely correlated with anti-Xa concentrations when compared to TBW and BMI. Dosing per EBV and TBW was the only variables associated with reaching target anti-Xa concentrations within the study. Further investigation is warranted to elucidate optimal EBV- and TBW-based dosing regimens., (© 2022 Pharmacotherapy Publications, Inc.)

Objective: Demonstrate the safety and efficacy of a standardized intravenous etomidate infusion protocol in normalizing cortisol levels in patients with severe and life-threatening hypercortisolism., Methods: A retrospective case series of seven patients representing nine episodes of severe hypercortisolism at two large academic medical centers was conducted. Patients were included in this series if they received an etomidate infusion for the treatment of severe and life-threatening hypercortisolism. The etomidate infusion was administered via a newly developed protocol designed to safely reduce cortisol levels until more long-term medical or definitive surgical therapy could be instituted., Results: Seven patients representing nine episodes received etomidate treatment. In eight of nine episodes of therapy, rapid control of hypercortisolemia was achieved, generally defined as a serum cortisol level of 10 to 20 µg/dL. Patients with a median baseline cortisol of 105 µg/dL (range, 32 to 245 µg/dL) achieved a median nadir serum cortisol of 15.8 µg/dL (range, 6.9 to 27 µg/dL) after a median of 38 hours (range, 26 to 134 hours)., Conclusions: A standardized continuous intravenous etomidate infusion protocol is a safe and effective means of achieving a serum cortisol level of 10 to 20 µg/dL in patients with severe hypercortisolemia.

Objective: To describe 2 cases of clinically significant phenytoin removal during continuous venovenous hemofiltration (CVVH) and review the relevant literature regarding phenytoin removal by renal replacement modalities., Case Summary: A 64-year-old female with chronic kidney disease and cirrhosis was admitted to the intensive care unit (ICU) with a traumatic subdural hematoma and seizures. The patient received a loading dose of intravenous phenytoin 1000 mg, followed by maintenance intravenous administration of phenytoin 100 mg and levetiracetam 250 mg every 12 hours. CVVH was initiated for acidosis. A 63-year-old male was admitted to the ICU after cardiac surgery complicated by hypotension. CVVH was initiated for fluid overload, and phenytoin was initiated 3 days later for seizures. A loading dose of intravenous phenytoin 2700 mg was administered, followed by maintenance dosing of intravenous phenytoin 150 mg every 8 hours. Concentrations of unbound phenytoin in serum and CVVH effluent samples were measured during concomitant treatment in each patient. In both patients, serum and effluent concentrations of unbound phenytoin fell steadily while they were on CVVH. Clearance of phenytoin by CVVH was calculated, as was the daily removal of phenytoin, as a percentage of total daily phenytoin dosage during each sampling period. Phenytoin clearance by CVVH ranged from 11 to 13 mL/min in these patients., Discussion: The clearance of phenytoin with CVVH in these 2 patients was much higher than the renal clearance of phenytoin reported in healthy volunteers with normal renal function. Previous case reports have demonstrated that only small, clinically insignificant amounts of phenytoin are removed by hemodialysis, and the only published report of phenytoin removal by continuous renal replacement therapy used hemofiltration rates much lower than those used in the 2 cases described here., Conclusions: These cases demonstrate that a substantial amount-approximately 30%-of total daily phenytoin dose may be removed by CVVH, and patients may require higher than expected empiric doses. Phenytoin concentrations should be closely monitored in critically ill patients receiving CVVH.

Multidrug-resistant pathogens have become increasingly common in contemporary healthcare. Specific to Gram-positive pathogens, methicillin-resistant Staphylococcus aureus (MRSA) is of particular concern, as it has been associated with increased hospital length of stay, higher healthcare expenditures and poorer outcomes. To date, linezolid is the first and only oxazolidinone approved by the US FDA for the treatment of infections caused by Gram-positive pathogens, including MRSA. This article will serve as a comprehensive review of linezolid, including an overview of the current market and its in vitro activity, with an in-depth review of its pharmacokinetic and pharmacodynamic profile. Emphasis will be placed on clinical data for the drug, both on- and off-label. The article will conclude with a brief overview of linezolid's pharmacoeconomic implications and safety profile, followed by a commentary and 5-year prospective analysis remarking on the future of the antimicrobial field as it relates to MRSA.

We argue that analyzing everyday memory failures in terms of the "unity of consciousness" can elucidate the bases of such failures. A perfect unity amongst one's mental states is rare. In extreme cases the unity of consciousness can breakdown in dramatic fashion (e.g., in Dissociative Identity Disorder), but such breakdowns also occur in less dramatic ways that affect us in everyday life. For example, disruptions in the unity of consciousness can result in everyday memory failures, such as forgetting to put on a tie for an important formal meeting. After providing some philosophical background into the notions of "unity of consciousness" and "functionalism," we offer preliminary analyses of three examples of everyday memory failure. We then introduce and develop what we call the "unity model" of memory failure and show how it explains the examples. We also describe different ways that unity can break down which, in turn, can lead to memory failure and inappropriate behavior. We then show how slips of action and other kinds of cognitive failures (e.g., memory blocks) differ from everyday memory failures. Finally, we examine alternative models (e.g., Absentmindedness and Multimodal) arguing that the unity model is preferable, and then show how our model is consistent with some experimental results.

In 4 experiments, the authors examined how several variables influence the quality and quantity of information that people use to make judgments about other people. The results showed that when possible, participants consistently responded appropriately to variables that influenced information that they used to make inferences about other minds. The results also suggested that under circumstances with no opportunity to contrast behavior in different situations, people might not be sensitive to the quality and quantity of information present. The authors interpreted results to mean that under most circumstances, people make inferences in a way that efficiently uses information about the causes of behavior.

Pneumococcal surface protein A (PspA) is a highly variable protein found on all strains of pneumococci. To be successful, a PspA-based vaccine for S. pneumoniae must induce antibodies that are broadly cross-reactive. To address whether cross-reactive antibodies could be induced in man, we evaluated serum from adults immunized with recombinant clade 2 PspA from strain Rx1. Immunization with 5-125 microg rPspA lead to a significant increase in circulating anti-PspA antibodies, as well as antibodies reactive to heterologous rPspA molecules. Increased binding of post-immune sera to 37 pneumococcal strains expressing a variety of PspA and capsule types was observed, versus pre-immune sera. The extent of cross-clade reactivity of human anti-rPspA followed roughly the amount of sequence homology to the non-clade 2 antigens. It is hypothesized that priming of humans by natural exposure to S. pneumoniae contributes to the breadth of the cross-reactivity of antibody to PspA.

Pharmacologic therapy plays a key role in the emergency resuscitation of patients with cardiac arrest. The Advanced Cardiac Life Support guidelines sanctioned by the American Heart Association provide flexible treatment protocols (algorithms) that serve as a valuable tool for clinicians. Vasoactive (vasopressive) therapy with epinephrine is of primary importance in all patients with nonperfusing rhythms (for example, ventricular fibrillation [VF], pulseless ventricular tachycardia [VT], electromechanical dissociation [EMD], and asystole) because it raises myocardial and cerebral perfusion pressures, thereby increasing the likelihood of successful resuscitation. Antiarrhythmic drugs play a secondary role to electrocardioversion in the treatment of VF and pulseless VT. Despite continued investigation and recent advances in our understanding of the role of drugs and other therapeutic interventions, the short-term and long-term prognoses of patients with cardiac arrest, especially out-of-hospital arrest, remain dismal. Clearly, much study into the prevention and treatment of sudden cardiac death is desperately needed.

Memory research, like other scientific research, disregards many variables in order to bring the full force of the scientific method to bear on clearly important variables. The reasons why memory research attends to certain variables and disregards others emanate largely from theoretical assumptions that distinguish memory systems from other psychological systems, and that distinguish variables intrinsic to memory from those extrinsic to memory. Nevertheless, a number of these 'forgotten' variables affect memory performance. Regardless of past practice, it is a mistake for memory research to continue to ignore relevant variables. Doing so introduces measurement error that contaminates memory performance measures, and classification error that precludes the discovery of legitimate memory variables. It is proposed here that if forgotten memory variables are controlled, manipulated, and measured more extensively, then future memory research will have greater power and memory theories will have greater validity.

This experiment tests the hypothesis that semantic relations are graded concepts. It also tests the predictions of relation element theory and of Klix's (1986) theory of semantic relations regarding possible predictors of graded structure for semantic relations. Results support the hypothesis that semantic relations have graded structures, and indicate that differences among relations in gradedness reflect the families of semantic relations described by Chaffin & Herrmann (1984). In addition, Klix's distinction between property relations and event relations appears to be useful in explaining differences among relations in graded structure.

Recent research has demonstrated that people hold beliefs about how well others perform everyday memory tasks according to another's sex. For example, meta-memory ratings indicate that other men and other women are believed to differ in their success at performing certain memory tasks (Crawford, Herrmann, Holdsworth, Randall & Robbins, 1989). In the present study, two experiments investigated whether gender stereotypes concerning everyday memory have any validity. Experiment 1 presented female and male subjects with two tasks that the aforementioned meta-memory ratings had shown are implicitly gender marked: learning a shopping list (a sterotypically feminine task) and learning directions to go to a particular place (a stereotypically masculine task). The results were consistent with the gender stereotypes, i.e. women recalled more of the shopping list than men whereas men recalled more of the directions than women. The second experiment investigated whether memory performance would be influenced by mere changes in the label of materials in memory tasks to be biased toward male or female gender background: labelling a shopping list as pertaining to 'groceries' or to 'hardware store'; and a set of directions to 'make a shirt' or to 'make a workbench'. The results also indicated that memory performance varied in ways consistent with gender stereotypes.

An international collaborative study was conducted at ten sites to examine the performance of enzyme immunoassays (EIAs) for the quantitation of IgG1, IgG2, IgG3, IgG4 and total IgG anti-Haemophilus influenzae type b (Hib) capsular polysaccharide in human serum. All groups used the same reagents: microtiter plates coated with polyribosylribitol phosphate (PRP) conjugated to poly-L-lysine (PLL), reference, control and test human sera, biotin-conjugated International Union of Immunological Societies (IUIS)-documented monoclonal anti-human IgG1-4 and IgG Pan detection antibodies, avidin-peroxidase and TMB substrate. Initial mixing of soluble PRP antigen or an equal volume of buffer with the 20 test sera prior to analysis confirmed PRP antigen specificity in all five EIAs with greater than 80% competitive inhibition at most sites. Positive correlation between the total IgG anti-Hib and sum of IgG1-4 anti-Hib was demonstrated (r2 = 0.99, Y = 1.13X -0.15). Good agreement was shown between the total IgG anti-Hib as measured by EIA and the total Hib-specific antibodies measured by the current radiolabeled antigen binding assay (r2 = 0.97, Y = 4.6X -5.8). Assay parallelism was demonstrated with an average interdilutional %CV of 22% and parallel dose-response curve slopes. The interdilutional %CVs were calculated as an average per sample of the variation of microgram/ml (corrected for dilution) at different dilutions per laboratory for all participating sites. The interlaboratory variation was the only performance parameter studied that exceeded the target level of 35% CV in all IgG1-4 and total IgG anti-Hib assays. IgG subclass distributions in the test sera demonstrated a predominance of IgG1 anti-Hib in the pediatric serum pools and IgG2 anti-Hib in the adult sera, with low but detectable levels of IgG3 and IgG4 anti-Hib in each group.

The notion that some memory processes are acquired has been around for at least two thousand years. However, acquired memory processes have been made the object of scientific investigation in only the past two decades. Traditionally, psychologists have assumed that acquired memory processes are equally effective across the entire range of memory tasks. This article reviews research that has investigated whether these processes are equally effective across tasks or are more effective for just certain tasks. The review indicates that most, if not all, acquired memory processes are biased to deal effectively just certain kinds of mental representation. The article proposes that these processes are representationally biased because (1) they activate basic memory processes (e.g. imagery, rehearsal) which themselves are biased to process certain representational attributes and because (2) their use of basic processes follows a sequence required by particular memory tasks. Increased understanding of the representational bias of acquired processes may be seen to enable better control of memory performance and to foster more powerful investigations of memory phenomena.

Undergraduate students were presented with word pairs (e.g., egg-yolk) and were timed as they decided whether one word named part of the thing named by the other word. In Experiment 1, "no" responses to nonpart pairs (e.g., fish-flaps) were slowed by the similarity of the stimulus part (flaps) to a part that the stimulus object did possess (fins). This suggested that decisions were made by retrieving parts of the stimulus object from memory and comparing them to the stimulus part. Whereas the parts used as stimuli in Experiment 1 were nonspecific, belonging to several different types of object (e.g., wheel), those selected for Experiment 2 were specific to a single type of object (e.g., thumb). In Experiment 2, "no" responses to nonpart pairs (e.g., foot-thumb) were slowed by similarity of the stimulus object (foot) to an object that the stimulus part (thumb) belonged to (hand). This suggested that decisions were made by retrieving the object to which the stimulus part belonged and comparing it to the stimulus object. The results support a hybrid model of part-whole decisions that includes directed retrieval of relational knowledge from memory and a comparison process.

Asplenic persons are at risk for the development of overwhelming sepsis from certain encapsulated bacteria, including meningococci. Since it is not known if asplenic persons can have antibody responses, this study compared such responses following bivalent groups A and C meningococcal polysaccharide vaccine in 22 asplenic subjects and healthy control subjects. There were no adverse reactions to the vaccine. Antibody responses were measured using a solid-phase radioimmune assay; results were compiled for both seroconversions and changes in mean antibody titers of IgG, IgA, and IgM classes. Subjects who underwent splenectomy for trauma and control subjects with spleens showed a polyclonal antibody response to both vaccine antigens. Those persons who underwent splenectomy for nonlymphoid tumors had nearly as good a response as normal subjects. By contrast, asplenic subjects with lymphoid tumors who had received prior chemotherapy and radiotherapy had poor responses to both antigens. It is concluded that meningococcal vaccine is immunogenic in asplenic persons, with the aforementioned exceptions, and that this vaccine should be routinely administered to such persons.

Subjects were presented with word pairs (e.g., bed-mattress) and timed as they decided whether one word named part of the item named by the other word. Yes responses were facilitated, and no responses were impeded, by relation similarity (i.e., the similarity of the relation between the two stimulus items to the part-whole relation). Item similarity, the similarity of the two stimulus items to each other, had no effect. The results support the view that similarity effects in semantic decision tasks are due to the comparison of elements of the relation between the two stimulus words against relation elements that serve as criteria for the target relation that the subject has been asked to identify.

In Experiment I, subjects made similarity judgments about all 56 category terms listed in the Battig and Montague (1969) norms. These judgments were then subjected to a hierarchical clustering analysis. Experiment II demonstrated that the relations among the category labels are very similar to the relations among the high dominance exemplars of these categories. Experiment III showed that the distances between the category terms in the hierarchical clustering analysis could predict RTs in a same-different paradigm.

In order to determine production frequencies for various category terms, 219 college students were asked to generate category terms (e.g. Automobiles, Vegetables, Relatives) during a 4-rain period. The production frequency (i.e., the number of subjects who listed a particular term) for a given category term may be considered as reflecting the familiarity or amount of usage of that category term, and, as such, should be of value to memory researchers in designing experiments. Additionally, examination of the order in which terms were produced showed that subjects "clustered" related category terms, (e.g., "Countries" and "States" were often produced successively). This clustering of category terrms is supportive of the hypothesis that categories are organized in semantic memory in some kind of higher order structure.

The present experiment investigated the effect of hemispheric dominance, as indicated by handedness, and perceptual processing. Displays containing two visual patterns were presented to right- and left-handed subjects who classified the two patterns as being the same or different. Also the two patterns in a display were in either an identical orientation or nonidentical orientations. Overall, left handers were faster than right handers at the "same-different" judgement. Additionally, latency increased with the angular discrepancy in orientation between patterns for both handedness groups but this increase was smaller for left handers than for right handers. Apparently, left handers evaluate overall perceptual similarity faster than right handers and they also mentally rotate perceived patterns of discrepant orientations faster than right handers. These findings contradict previous generalizations that left handers are deficient perceptually. Moreover, the present results support the position that left handers should be faster at global perceptual tasks because left handers have less neural distance than right handers mediating the transmission of information between the locus of perception and the locus of dominance.