Empirical antimicrobial prescribing for pyelonephritis in patients discharged from 15 US Emergency Departments: an opportunity for improvement.

BACKGROUND: Urinary tract infections (UTIs) are commonly treated in the emergency department (ED), and unfortunately, resistance to first-line agents is increasing. OBJECTIVES: To characterize treatment of pyelonephritis in a nationally representative sample of ED patients and to identify patient- and treatment-specific factors associated with receiving initial inactive antibiotics. METHODS: We conducted a multicentre, observational cohort study utilizing the Emergency Medicine PHARMacotherapy Research NETwork (EMPHARM-NET), comprising 15 geographically diverse US EDs. All patients ≥18 years of age with a diagnosis of pyelonephritis between 2018 and 2020 were included. The primary endpoint was the proportion of patients who received initial inactive empirical antibiotic therapy and to identify predictive factors of inactive antibiotic therapy. RESULTS: Of the 3714 patients evaluated, 223 had culture-positive pyelonephritis. Median patient age was 50.1 years and patients were mostly female (78.3%). Overall, 40.4% of patients received an IV antibiotic, most commonly ceftriaxone (86.7%). The most frequently prescribed antibiotics were cefalexin (31.8%), ciprofloxacin (14.3%), cefdinir (13.5%) and trimethoprim/sulfamethoxazole (12.6%). Overall, 10.3% of patients received initial inactive therapy. After adjustment in a multivariable analysis, long-acting IV antibiotic was predictive of inactive therapy (OR 0.23, 95% CI 0.07-0.83). CONCLUSIONS: In our prospective, multicentre observational study, we found that only 40.4% of patients with pyelonephritis received empirical IV antibiotics in the ED, contributing to inactive therapy. Receipt of long-acting IV antibiotics was independently associated with a decreased rate of initial inactive therapy. This reinforces guideline recommendations to administer long-acting IV antibiotics empirically in the ED upon suspicion of pyelonephritis.

EDucated: The emergency medicine pharmacotherapy literature of 2023.

The purpose of this article is to summarize pharmacotherapy related emergency medicine (EM) literature indexed in 2023. Articles were selected utilizing a modified Delphi approach. The table of contents from pre-determined journals were reviewed and independently evaluated via the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system by paired authors. Pharmacotherapy-related publications deemed to be GRADE 1A and 1B were reviewed by the collective group for inclusion in the review. In all, this article summarizes and provides commentary on the potential clinical impact of 13 articles, 6 guidelines, and 5 meta-analyses covering topics including guideline releases and updates on rapid sequence intubation in the critically ill, managing cardiac arrest or life-threatening toxicity due to poisoning, and management of major bleeding following trauma. Also discussed are ongoing controversies surrounding fluid resuscitation, time and treatment modalities for ischemic stroke, steroid use in community-acquired pneumonia, targeted blood product administration, and much more.

UpdatED: The emergency medicine pharmacotherapy literature of 2022.

The purpose of this article is to summarize pharmacotherapy related emergency medicine (EM) literature indexed in 2022. Articles were selected utilizing a modified Delphi approach. The table of contents from pre-determined journals were reviewed and independently evaluated via the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system by paired authors, with disagreements adjudicated by a third author. Pharmacotherapy-related publications deemed to be GRADE 1A and 1B were reviewed by the group for inclusion in the review. In all, this article summarizes and provides commentary on the potential clinical impact of 13 articles, 4 guidelines, and 3 meta-analyses covering topics including anticoagulant reversal, tenecteplase in acute ischemic stroke, guideline updates for heart failure and aortic aneurysm, magnesium in atrial fibrillation, sedation in mechanically ventilated patients and pain management strategies in the Emergency Department (ED), and tranexamic acid use in epistaxis and GI bleed.

Emergency Department Management of Uncomplicated Hyperglycemia in Patients without History of Diabetes.

BACKGROUND: Hyperglycemia is a common finding in patients presenting to the emergency department (ED). Recommendations addressing uncomplicated hyperglycemia in the ED are limited, and the management of those without a prior diagnosis of diabetes presents a challenge. OBJECTIVE: This narrative review will discuss the ED evaluation and management of hyperglycemic adult patients without a history of diabetes who do not have evidence of a hyperglycemic crisis, such as diabetic ketoacidosis or hyperosmolar hyperglycemic state. DISCUSSION: Many adults who present to the ED have risk factors for diabetes and meet American Diabetes Association (ADA) criteria for diabetes screening. A new diagnosis of type 2 diabetes can be established in the ED by the ADA criteria in patients with a random plasma glucose ≥ 200 mg/dL (11.1 mmol/L) and symptoms of hyperglycemia. The diagnosis should be considered in patients with an elevation in random blood glucose > 140 mg/dL (7.8 mmol/L). Treatment may begin in the ED and varies depending on the presenting severity of hyperglycemia. Treatment options include metformin, long-acting insulin, or deferring for close outpatient management. CONCLUSIONS: Emergency clinician knowledge of the evaluation and management of new-onset hyperglycemia and diabetes is important to prevent long-term complications.

The Emergency Medicine Pharmacotherapy Literature of 2021.

This article highlights the most relevant emergency medicine (EM) pharmacotherapy publications indexed in 2021. A modified Delphi approach was utilized for selected journals to identify the most impactful EM pharmacotherapy studies via the GRADE system. After review of journal table of contents GRADE 1A and 1B articles were reviewed by authors. Twenty articles, 2 guidelines, 2 position papers, and 2 meta-analysis were selected for full summary. Articles included in this review highlight acute agitation management, acute appendicitis treatment, sexually transmitted infection updates, optimizing sepsis management and treatment, updates for the ideal thrombolytic agent in acute ischemic stroke and endovascular therapy candidates, indications for tranexamic acid, calicium for out of hospital cardiac arrest, optimial inotrope for cardiogenic shock, awareness during rapid sequence intubation paralysis, comparison of propofol or dexmedetomidine for sedation, treatment of cannabis hyperemsis syndrome, and prophylactic use of diphenhydramine to reduce neuroleptic side effects. Selected articles are summarized to include design, results, limitations, conclusions and impact.

Dorsomedial prefrontal neural ensembles reflect changes in task utility that culminate in task quitting.

When performing a physically demanding behavior, sometimes the optimal choice is to quit the behavior rather than persist to minimize energy expenditure for the benefits gained. The dorsomedial prefrontal cortex (dmPFC), consisting of the anterior cingulate cortex and secondary motor area, likely contributes toward such utility assessments. Here, we examined how male rat dmPFC single unit and ensemble-level activity corresponded to changes in task utility and quitting in an effortful weight lifting task. Rats carried out two task paradigms: one that became progressively more physically demanding over time and a second fixed effort version. Rats could quit the task at any time. Dorsomedial PFC neurons were highly responsive to each behavioral stage of the task, consisting of rope pulling, reward retrieval, and reward area leaving. Activity was highest early in sessions, commensurate with the highest relative task utility, then decreased until the point of quitting. Neural ensembles consistently represented the sequential behavioral phases of the task. However, these representations were modified over time and became more distinct over the course of the session. These results suggest that dmPFC neurons represent behavioral states that are dynamically modified as behaviors lose their utility, culminating in task quitting.NEW & NOTEWORTHY When carrying out a physically demanding task, animals must continually assess whether to persist or quit. In this study, we recorded neurons in the dorsomedial prefrontal cortex (dmPFC) of rats as they carried out a challenging weightlifting task, up to the point of quitting. We demonstrate that dmPFC neurons form a representation of the task that is modified, via a decrease in firing rate, by the decreasing the utility of the task that may signal quitting.

The Association of ICH Exclusion Criteria With Mortality and Disability Rates in ICH Patients Receiving 4F-PCC for Anticoagulation Reversal.

BACKGROUND: Intracranial hemorrhage (ICH) exclusion criteria in the landmark four-factor prothrombin complex concentrate (4F-PCC) trial have not been incorporated into clinical practice and incremental predictive ability is unknown. OBJECTIVES: Evaluate the association of meeting at least 1 ICH exclusion criterion with the composite end point in-hospital mortality and modified Rankin Scale [mRS] score 5 or 6. Determine the number and combination of criteria associated with poor outcomes. METHODS: Retrospective review of adult ICH patients who received 4F-PCC for anticoagulant reversal. Patient demographics, ICH exclusion criteria, in-hospital mortality, disability, and disposition were collected. χ2 Analysis and logistic regression were used to assess differences between patients with and without ICH exclusion criteria. RESULTS: Data from 167 patients were analyzed: 103 (61.7%) met at least 1 ICH exclusion criterion. The composite end point occurred more in those with at least 1 ICH exclusion criterion (74.8% vs 39%; P < 0.0001). Presence of 2 or more ICH exclusion criteria was associated with higher odds of the composite end point, higher mRS score, and long-term care facility disposition (P < 0.0001). Glasgow Coma Scale score <7 and at least 1 other ICH exclusion criterion had negative effects on composite end point and mortality: 95% to 100% and 85% to 100%, respectively. CONCLUSION AND RELEVANCE: Patients meeting at least 1 ICH exclusion criterion had greater death/disability compared with those who did not. More ICH exclusion criteria were associated with higher rates of death, disability, and worse disposition. These data may aid in developing optimal 4F-PCC use criteria.

High-dose nitroglycerin infusion for the management of sympathetic crashing acute pulmonary edema (SCAPE): A case series.

Sympathetic crashing acute pulmonary edema (SCAPE) describes the most severe presentation of acute heart failure (AHF). Immediate intervention is required to prevent hemodynamic decompensation and endotracheal intubation. Although high-dose nitroglycerin (>100 µg/min) has been described for this clinical scenario in limited case reports, the concern for adverse effects such as hypotension and syncope limit providers comfortability in initiating nitroglycerin at these doses. Described here is a case series of four patients who safely and effectively received high-dose nitroglycerin infusions for the management of SCAPE.

Staying InformED: Top emergency Medicine pharmacotherapy articles of 2020.

The year 2020 was not easy for Emergency Medicine (EM) clinicians with the burden of tackling a pandemic. A large focus, rightfully so, was placed on the evolving diagnosis and management of patients with COVID-19 and, as such, the ability of clinicians to remain up to date on key EM pharmacotherapy literature may have been compromised. This article reviews the most important EM pharmacotherapy publications indexed in 2020. A modified Delphi approach was utilized for selected journals to identify the most impactful EM pharmacotherapy studies. A total of fifteen articles, eleven trials and four meta-analyses, were identified. This review provides a summary of each study, along with a commentary on the impact to the EM literature and EM clinician.

What is the Role of Sugammadex in the Emergency Department?

BACKGROUND: Sugammadex is a medication newly available to many emergency physicians. It effectively, and within minutes, reverses neuromuscular blockade in patients who have received rocuronium or vecuronium. The role of sugammadex for the reversal of neuromuscular blockade after rapid sequence intubation in the emergency department (ED) is evolving, and limited emergency medicine-specific literature exists. OBJECTIVE: This narrative review evaluates the role of sugammadex for the reversal of neuromuscular blockade in the ED. DISCUSSION: The basic pharmacology, duration of action, adverse effects, and important medication and disease interactions specific to sugammadex are well described. Case reports suggest sugammadex can reverse neuromuscular blockade to facilitate an urgent, neurologic examination by an emergency physician or consultant. Multiple case reports of failure to improve airway patency with the use of sugammadex, even when neuromuscular blockade is completely reversed, and concern for added difficulty of definitive airway management in a patient with spontaneous movement suggest that sugammadex should largely be omitted from failed or difficult airway management strategies. Instead, it is important to focus on the ability to oxygenate and ventilate, including progression to surgical airway or jet ventilation if needed. CONCLUSION: Sugammadex is an effective, rapid reversal agent for rocuronium and has the potential use to facilitate an urgent neurologic examination shortly after administration of rocuronium. Its routine inclusion in a failed or difficult emergency airway is not supported by available literature.

Prenatal diagnosis of middle interhemispheric variant of holoprosencephaly: Report of two cases.

Holoprosencephaly ranges in severity based on the degree of anatomic abnormality. Middle interhemispheric variant of holoprosencephaly is a less common and often milder variant that has the characteristic sonographic findings of an absent cavum septum pellucidum and a single fused ventricle. This subtype may be associated with genetic conditions that have not been well-described in the literature. We present two cases of middle interhemispheric variant of holoprosencephaly diagnosed on fetal ultrasound.

Delay activity in the Wulst of pigeons (Columba livia) represents correlates of both sample and reward information.

The avian Wulst is the pallial (analogous to mammalian cortex) termination point of the thalamofugal pathway, one of two main visual pathways in birds, and is considered to be equivalent to primate striate cortex. We recorded neuronal activity from the Wulst in pigeons during two versions of a delayed matching-to-sample procedure. Two birds were trained on a common outcomes (CO) procedure, in which correct responses following both the skateboarder and the flower stimuli were associated with reward. Two other birds were trained on a differential outcomes (DO) procedure in which correct responses following only the skateboarder stimulus were associated with reward, while correct responses following the flower stimulus were not rewarded. In line with previous studies, under CO conditions, and for both excitatory and inhibitory neurons, delay activity in the Wulst was significantly different from baseline activity following both sample stimuli, which may indicate that Wulst delay activity is a neural correlate of working memory for the sample stimulus. On the other hand, under DO conditions, Wulst delay activity appeared to be a neural correlate of the upcoming reward. We argue that Wulst neurons display flexibility in their encoding in that they can encode both sample and reward information, but may default to one type of coding over the other based on the demands of the task. The current study provides the first evidence that delay activity in the Wulst represents both a neural correlate for sample information as well as reward information.

Anterior cingulate cortex encoding of effortful behavior.

An animal's ability to assess the value of their behaviors to minimize energy use while maximizing goal achievement is critical to its survival. The anterior cingulate cortex (ACC) has been previously shown to play a critical role in this behavioral optimization process, especially when animals are faced with effortful behaviors. In the present study, we designed a novel task to investigate the role of the ACC in evaluating behaviors that varied in effort but all resulted in the same outcome. We recorded single unit activity from the ACC as rats ran back and forth in a shuttle box that could be tilted to different tilt angles (0, 15, and 25°) to manipulate effort. Overall, a majority of ACC neurons showed selective firing to specific effort conditions. During effort expenditure, ACC units showed a consistent firing rate bias toward the downhill route compared with the more difficult uphill route, regardless of the tilt angle of the apparatus. Once rats completed a run and received their fixed reward, ACC units also showed a clear firing rate preference for the single condition with the highest relative value (25° downhill). To assess effort preferences, we used a choice version of our task and confirmed that rats prefer downhill routes to uphill routes when given the choice. Overall, these results help to elucidate the functional role of the ACC in monitoring and evaluating effortful behaviors that may then bias decision-making toward behaviors with the highest utility. NEW & NOTEWORTHY We developed a novel effort paradigm to investigate how the anterior cingulate cortex (ACC) responds to behaviors with varied degrees of physical effort and how changes in effort influence the ACC's evaluation of behavioral outcomes. Our results provide evidence for a wider role of the ACC in its ability to motivate effortful behaviors and evaluate the outcome of multiple behaviors within an environment.

Hippocampal place cell encoding of sloping terrain.

Effective navigation relies on knowledge of one's environment. A challenge to effective navigation is accounting for the time and energy costs of routes. Irregular terrain in ecological environments poses a difficult navigational problem as organisms ought to avoid effortful slopes to minimize travel costs. Route planning and navigation have previously been shown to involve hippocampal place cells and their ability to encode and store information about an organism's environment. However, little is known about how place cells may encode the slope of space and associated energy costs as experiments are traditionally carried out in flat, horizontal environments. We set out to investigate how dorsal-CA1 place cells in rats encode systematic changes to the slope of an environment by tilting a shuttle box from flat to 15 ° and 25 ° while minimizing external cue change. Overall, place cell encoding of tilted space was as robust as their encoding of flat ground as measured by traditional place cell metrics such as firing rates, spatial information, coherence, and field size. A large majority of place cells did, however, respond to slope by undergoing partial, complex remapping when the environment was shifted from one tilt angle to another. The propensity for place cells to remap did not, however, depend on the vertical distance the field shifted. Changes in slope also altered the temporal coding of information as measured by the rate of theta phase precession of place cell spikes, which decreased with increasing tilt angles. Together these observations indicate that place cells are sensitive to relatively small changes in terrain slope and that terrain slope may be an important source of information for organizing place cell ensembles. The terrain slope information encoded by place cells could be utilized by efferent regions to determine energetically advantageous routes to goal locations.

Maternal-Fetal Medicine Physician and Fellow Perceptions of Business in Medicine.

OBJECTIVE: Principles of practice management provide a foundation for clinical success and performance improvement. Scant data exist regarding maternal-fetal medicine (MFM) physicians' knowledge of these topics. We hypothesize that physicians enter practice with inadequate education in practice management. STUDY DESIGN: Surveys were emailed to members of the Society for Maternal-Fetal Medicine rating their knowledge and capabilities in practice management topics, and respondents assessed their current institution's business in the medical curriculum. RESULTS: A total of 325 (14.4%) physicians responded: 63 fellows in training and 262 MFM physician subspecialists. Practicing physicians reported learning most of their knowledge "in practice after fellowship" (85%) or "never at all" (10%). Only 3% of respondents had adequate business education during fellowship, and only 5% felt prepared to teach business principles. However, 85% of those surveyed agreed that this material should be taught during the fellowship. Among MFM subspecialists and fellows in training at institutions with fellowships, 60% reported no current curriculum for practice management, and those with current curricula reported it had "limited" or "no value" (76%). CONCLUSION: There is a significant desire for practice management curricula during MFM fellowship, and current training is insufficient. With many MFM physicians ill-prepared to teach these principles, professional education from other financial fields, and standardized education in practice management from current expert sources is needed.

Orbitofrontal cortex encodes memories within value-based schemas and represents contexts that guide memory retrieval.

There are a substantial number of studies showing that the orbitofrontal cortex links events to reward values, whereas the hippocampus links events to the context in which they occur. Here we asked how the orbitofrontal cortex contributes to memory where context determines the reward values associated with events. After rats learned object-reward associations that differed depending on the spatial context in which the objects were presented, neuronal ensembles in orbitofrontal cortex represented distinct value-based schemas, each composed of a systematic organization of the representations of objects in the contexts and positions where they were associated with reward or nonreward. Orbitofrontal ensembles also represent the different spatial contexts that define the mappings of stimuli to actions that lead to reward or nonreward. These findings, combined with observations on complementary memory representation within the hippocampus, suggest mechanisms through which prefrontal cortex and the hippocampus interact in support of context-guided memory.

The Role of Nicotinamide Phosphoribosyltransferase in Pregnancy: A Review.

Nicotinamide phosphoribosyltransferase (NAMPT) was first reported in 1994 and has been explored in various human disease processes. However, until recently, very little has been done to define the role of NAMPT in pregnancy. NAMPT is a 52 kDa protein that has diverse functions in the human body, acting as a growth factor, cytokine, an enzyme, and an insulinomimetic agent. Initial studies examined NAMPT expression in fetal membranes and its effects on the amnion. Later research in nonpregnant studies showed an insulinomimetic effect, and attention focused on its role in gestational diabetes. In addition, as studies revealed NAMPT's function as an inflammatory cytokine, studies examined NAMPT in preeclampsia and fetal growth restriction. Several studies have confirmed that NAMPT is a marker of systemic infectious processes such as pyelonephritis and intrauterine infection. In this review, we present the current understanding of NAMPT's role in various pregnancy-related conditions as well as possible directions for future research.

A clinical decision rule identifies risk factors associated with antimicrobial-resistant urinary pathogens in the emergency department: a retrospective validation study.

BACKGROUND: Identifying patients at high risk for multidrug-resistant urinary tract infections (UTIs) is important for guiding empirical antimicrobial therapy. Clinical risk factors associated with antimicrobial-resistant urinary pathogens and the derivation of a simple clinical decision rule could help define health care-associated UTI. OBJECTIVE: To derive a simple clinical decision rule to identify clinical risk factors associated with antimicrobial-resistant urinary pathogens. METHODS: This was a retrospective case-control study of all emergency department (ED) patients from July 1, 2011, to July 1, 2012, who presented to the ED with UTI and a positive urine culture. Candidate risk factors were collected retrospectively from medical record review. We compared differences in patient characteristics stratified by the presence of an antimicrobial-resistant urinary pathogen. RESULTS: A total of 360 patients with UTI had a positive, noncontaminated urine culture during the study period. About 6.7% of patients (n = 24) had a multidrug-resistant (MDR) urinary infection. Logistic regression modeling identified 3 clinical factors associated with the identification of a MDR pathogen: male sex, chronic hemodialysis, and nursing home residence. A scoring system was created to identify patients with MDR pathogens. Test characteristics were calculated using bootstrapping for internal validation, with a sensitivity of 74.7% (95% CI = 55.1%-91.3%) and specificity of 85.1% (95% CI = 77.8%-86.2%), positive likelihood ratio of 4.3, and a negative likelihood ratio of 0.3. CONCLUSIONS: Clinical factors can be used to identify UTI patients at high risk of MDR urinary pathogens.

Ultrasonographic Fetal Weight Estimation: Should Macrosomia-Specific Formulas Be Utilized?

OBJECTIVE: This study aims to derive an estimated fetal weight (EFW) formula in macrosomic fetuses, compare its accuracy to the 1986 Hadlock IV formula, and assess whether including maternal diabetes (MDM) improves estimation. STUDY DESIGN: Retrospective review of nonanomalous live-born singletons with birth weight (BWT) ≥ 4 kg and biometry within 14 days of birth. Formula accuracy included: (1) mean error (ME = EFW - BWT), (2) absolute mean error (AME = absolute value of [1]), and (3) mean percent error (MPE, [1]/BWT × 100%). Using loge BWT as the dependent variable, multivariable linear regression produced a macrosomic-specific formula in a "training" dataset which was verified by "validation" data. Formulas specific for MDM were also developed. RESULTS: Out of the 403 pregnancies, birth gestational age was 39.5 ± 1.4 weeks, and median BWT was 4,240 g. The macrosomic formula from the training data (n = 201) had associated ME = 54 ± 284 g, AME = 234 ± 167 g, and MPE = 1.6 ± 6.2%; evaluation in the validation dataset (n = 202) showed similar errors. The Hadlock formula had associated ME = -369 ± 422 g, AME = 451 ± 332 g, MPE = -8.3 ± 9.3% (all p < 0.0001). Diabetes-specific formula errors were similar to the macrosomic formula errors (all p = NS). CONCLUSIONS: With BWT ≥ 4 kg, the macrosomic formula was significantly more accurate than Hadlock IV, which systematically underestimates fetal/BWT. Diabetes-specific formulas did not improve accuracy. A specific formula should be considered when macrosomia is suspected.

Impact of sickle hemoglobinopathies on pregnancy-related venous thromboembolism.

OBJECTIVE: The aim of the study is to examine the relationship between sickle cell trait (Hb AS) and other sickle hemoglobinopathies and the risk of thromboembolism during pregnancy or the puerperium. STUDY DESIGN: Retrospective cohort study of African American women receiving prenatal care from 1991 to 2006. Sickle cell status was ascertained by routine hemoglobin electrophoresis. Venous thromboembolism (VTE) was defined as one or more episodes of deep venous and/or pulmonary thromboembolism during pregnancy or the puerperium according to discharge diagnoses based on International Classification of Diseases, Ninth Revision codes. RESULTS: Among 22,140 women with hemoglobin (Hb) AA status, 20 women (0.09%) experienced pregnancy-related VTE compared with 3 women (0.15%) of 2,037 women with Hb AS; relative risk (RR) for the association with AS status = 1.6; 95% confidence interval (CI) 0.5 to 5.5. Of 103 women, 3 women (2.9%) with sickle cell disease conditions (Hb SS, Hb SC, or Hb S,beta-thalassemia) experienced thromboembolism. Compared with women with Hb AA status, the RR = 32.2, 95% CI 9.7 to 107. CONCLUSION: Sickle cell trait may be associated with a modest increase in VTE in the setting of pregnancy; sickle cell disease conditions are strongly associated with this rare but potentially fatal outcome.