Intravenous Acetaminophen Versus Ketorolac for Prehospital Analgesia: A Retrospective Data Review.

BACKGROUND: Parenteral ketorolac and intravenous (IV) acetaminophen have been used for prehospital analgesia, yet limited data exist on their comparative effectiveness. STUDY OBJECTIVES: To evaluate the comparative effectiveness of IV acetaminophen and parenteral ketorolac for analgesia in the prehospital setting. METHODS: We conducted a retrospective cross-sectional evaluation of patients receiving IV acetaminophen or parenteral ketorolac for pain management in a large suburban EMS system between 1/1/2019 and 11/30/2021. The primary outcome was change in first to last pain score. Subgroup analysis was performed on patients with traumatic pain. We used inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) to estimate the treatment effect of acetaminophen versus ketorolac among all patients and the subgroup of those with traumatic pain. RESULTS: Of 2178 patients included, 856 (39.3%) received IV acetaminophen and 1322 (60.7%) received parenteral ketorolac. The unadjusted mean change in pain score was -1.9 (SD 2.4) for acetaminophen group and -2.4 (SD 2.4) for ketorolac. In the propensity score analyses, there was no statistically significant difference in pain score change for the acetaminophen group versus ketorolac among all patients (mean difference, IPTW: 0.11, 95% confidence interval [CI] -0.16, 0.37; PSM: 0.15, 95% CI -0.13, 0.43) and among those with traumatic pain (unadjusted: 0.18, 95% CI -0.35, 0.72; IPTW: 0.23, 95% CI -0.25, 0.71; PSM: -0.03, 95% CI -0.61, 0.54). CONCLUSIONS: We found no statistically significant difference in mean pain reduction of IV acetaminophen and parenteral ketorolac for management of acute pain.

Remote dielectric sensing for detecting pulmonary edema in the emergency department.

BACKGROUND: Dyspnea is a common Emergency Department (ED) complaint of which acute pulmonary edema (APE) is a potentially life-threatening etiology. Remote Dielectric Sensing (ReDS™) is a novel, non-invasive, radar based, rapid, point of care vest testing system used to objectively quantify lung fluid content and may be useful in the early diagnosis of APE. OBJECTIVE: To determine the accuracy of ReDS to detect pathologic lung fluid in ED undifferentiated dyspneic patients. METHODS: We performed a prospective convenience sample observation pilot study enrolling adult ED patients with a chief complaint of "shortness of breath." After informed consent, patients were fitted with the ReDS vest and a reading, blinded to the care team, was recorded. A gold standard diagnosis of pulmonary edema, determined by 2 physicians performing a chart review and blinded to ReDs data, was compared to the ReDS reading. RESULTS: Overall, 123 patients were included; 59% (n = 73) were male, mean (SD) age 57.2 (±12) years, 46.3% (n = 57) Hispanic, 34.1%(n = 42) African American, 13.0% (n = 16) Caucasian and 5.7% (n = 7) Asian. The gold standard diagnosis showed pulmonary edema in 38 (30.9%) patients, of which 30 were detected by ReDS. At an optimal cutoff (≥ 37%), ReDS had a Sn of 79.5% (CI 63.5% - 90.5%), Sp of 72.6% (CI 61.8% - 81.8%), a PPV of 57.4% and a NPV of 88.4%. CONCLUSIONS: ReDS is moderately sensitive and specific with an accuracy of 74.8% for pulmonary edema.

Validation of the bacterial meningitis score in adults presenting to the ED with meningitis.

OBJECTIVES: The Bacterial Meningitis Score classifies children with meningitis and none of the following high-risk predictors at very low risk for bacterial meningitis: positive cerebrospinal fluid (CSF) Gram stain, CSF protein ≥80mg/dL, CSF absolute neutrophil count (ANC) ≥1000 cells/mm(3), peripheral ANC ≥10,000 cells/mm(3), and seizure at or prior to presentation. Although extensively validated in children, the Bacterial Meningitis Score has not been rigorously evaluated in adults. METHODS: We performed a single-center cross-sectional retrospective study of adults presenting to the emergency department between 2003 and 2013 with meningitis (defined by CSF white blood cell count ≥10 cells/mm(3)). We defined a case of bacterial meningitis with either a positive CSF or blood culture. We report the performance of the Bacterial Meningitis Score in the study population. RESULTS: We identified 441 eligible patients of which, 4 (1%) had bacterial meningitis. The Bacterial Meningitis Score had a sensitivity of 100% [95% confidence interval (CI) 40%-100%], specificity 51% (95% CI, 46%-56%) and negative predictive value of 100% (95% CI, 98%-100%). None of the low risk adults had bacterial meningitis. If Bacterial Meningitis Score had been applied prospectively, the hospital admission rate would have dropped from 84% to 49% without missing any patients with bacterial meningitis. CONCLUSIONS: The Bacterial Meningitis Score accurately identified patients at low risk for bacterial meningitis and could assist clinical decision-making for adults with meningitis.

Perceptions of basic, advanced, and pediatric life support training in a United States medical school.

BACKGROUND: Basic Life Support (BLS), Advanced Cardiac Life Support (ACLS), and Pediatric Advanced Life Support (PALS) are integral parts of emergency resuscitative care. Although this training is usually reserved for residents, introducing the training in the medical student curriculum may enhance acquisition and retention of these skills. OBJECTIVES: We developed a survey to characterize the perceptions and needs of graduating medical students regarding BLS, ACLS, and PALS training. METHODS: This was a study of graduating 4th-year medical students at a U.S. medical school. The students were surveyed prior to participating in an ACLS course in March of their final year. RESULTS: Of 152 students, 109 (71.7%) completed the survey; 48.6% of students entered medical school without any prior training and 47.7% started clinics without training; 83.4% of students reported witnessing an average of 3.0 in-hospital cardiac arrests during training (range of 0-20). Overall, students rated their preparedness 2.0 (SD 1.0) for adult resuscitations and 1.7 (SD 0.9) for pediatric resuscitations on a 1-5 Likert scale, with 1 being unprepared. A total of 36.8% of students avoided participating in resuscitations due to lack of training; 98.2%, 91.7%, and 64.2% of students believe that BLS, ACLS, and PALS, respectively, should be included in the medical student curriculum. CONCLUSIONS: As per previous studies that have examined this topic, students feel unprepared to respond to cardiac arrests and resuscitations. They feel that training is needed in their curriculum and would possibly enhance perceived comfort levels and willingness to participate in resuscitations.

Treatment of Presumed Hyperkalemia in the Prehospital Setting.

INTRODUCTION: Hyperkalemia (HK) is common and potentially a life-threatening condition. If untreated, HK can progress to ventricular arrhythmia and cardiac arrest. Early treatment reduces mortality in HK. This study evaluates a novel protocol for identification and empiric management of presumed HK in the prehospital setting. METHODS: This was a retrospective, observational chart review of a single, large, suburban Emergency Medical Services (EMS) system. Patients treated for presumed HK, with both a clinical concern for HK and electrocardiogram (ECG) changes consistent with HK, from February 2018 through February 2021 were eligible for inclusion. Patients were excluded if found to be in cardiac arrest on EMS arrival. Empiric treatment of HK included administration of calcium, sodium bicarbonate, and albuterol. Post-treatment, patients were placed on cardiac monitoring and adverse events recorded enroute to receiving hospital. Protocol compliance was assessed by two independent reviewers. Serum potassium (K) level was obtained from hospital medical records. RESULTS: A total of 582 patients were treated for HK, of which 533 patients were excluded due to cardiac arrest prior to EMS arrival. The remaining 48 patients included in the analysis had a mean age of 56 (SD = 20) years and were 60.4% (n = 29) male with 77.1% (n = 37) Caucasian, 10.4% (n = 5) African American, and 12.5% (n = 6) Hispanic. Initial blood draw at the receiving facilities showed K >5.0mEq/L in 22 (45.8%), K of 3.5-5.0mEq/L in 23 (47.9%), and K <3.5mEq/L in three patients (6.3%). Independent review of the EMS ECG found the presence of hyperkalemic-related change in 43 (89.6%) cases, and five (10.4%) patients did not meet criteria for treatment due to lack of either appropriate ECG findings or clinical suspicion. No episodes of unstable tachyarrhythmia or cardiac arrest occurred during EMS treatment or transport. CONCLUSION: The study evaluated a novel protocol for detecting and managing HK in the prehospital setting. It is feasible for EMS crews to administer this protocol, although a larger study is needed to make the results generalizable.

Aligning physiology with psychology: Translational neuroscience in neuropsychiatric drug discovery.

This review presents an overview of some of the pre-clinical and clinical issues that have contributed to the failures of potential novel neuropsychiatric drugs, which have prompted a re-examination of the role of animal models of neuropsychiatric disorders. Advances both in basic neuroscience and technology have driven the development of animal models of aspects of neuropsychiatric disorders. Genetics and environmental factors have been the primary contributors to the development of new animal models. Neuroimaging has contributed to the search for biomarkers by which neuropsychiatric disorders may be identified and differentiated, its progression monitored and that the effects of therapy assessed. Parallel to these theoretical and practical advancements have been the changes in the diagnosis and classification of neuropsychiatric disorders from DSM-4 to DSM-5, and emergence of the NIH initiatives such as MATRICS; CNTRICS and RDoC. These latter changes are shifting our concepts of neuropsychiatric disorders away from phenomenology to their biology and thus aligning physiology with psychology.

Animal models of depression in drug discovery: a historical perspective.

Over the course of the last 50 years many models of major depressive disorder have been developed on the basis of theoretical aspects of this disorder. These models and procedures have been crucial in the discovery and development of clinically-effective drugs. Notwithstanding, there is presently great concern about the discrepancy between positive outcomes of new candidate drugs in animal models and apparent lack of efficacy in humans i.e., the predictive validity of animal models. Some reasons for this concern lie in the over-reliance in the face value of behavioural models, design of clinical trials, placebo responses, genetic variations in response to drugs, species differences in bioavailability and toxicology, and not least, disinterest of pharmaceutical sponsors to continue developing certain drugs. Present model development is focusing on endophenotypic aspects of behaviours rather than trying to model whole syndromes. This essay traces the origins and theoretical bases of our animal models of depression or depressed-like behaviours in humans and indicates how they have evolved from behavioural assays used to measure the potency and efficacy of potential candidate drugs to tools by which endophenotypes of depression may be identified and verified pharmacologically. A cautionary note is included though to indicate that the true predictive validity of our models will not be fully assessed until we can determine the attrition rate of molecules discovered from new drug targets translating into clinically-effective drugs.

Current Status of Hemostatic Agents and Sealants in Urologic Surgical Practice.

There has been a recent and near exponential increase in the use of hemostatic agents and sealants to supplement the rapidly evolving methods in the surgical management of urologic patients. This article reviews the use of hemostatic agents and sealants in current urologic practice.

Effects of acute administration of DA agonists on locomotor activity: MPTP versus neonatal intracerebroventricular 6-OHDA treatment.

The effects of several dopamine (DA) receptor agonists upon locomotor activity on adult MPTP-treated mice and postnatal 6-hydroxydopamine- (6-OHDA-) treated rats were assessed in ten experiments. C57 BL/6 mice were administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 2 x 40 mg/kg, s.c., 24-hr interval between injections) at 5-months-age, while 1-day-old male Wistar rat pups were given intracisternal 6-OHDA (50 mg, once following desipramine, 25 mg/kg). MPTP-treated mice were tested 4-5 weeks following MPTP injections whereas neonatal 6-OHDA rats were tested at 3-months-age. Locomotor activity was measured in respective activity test chambers following acute administration of DA receptor agonists. In MPTP-treated mice, apomorphine failed to elevate locomotor activity but instead further exacerbated (1.0 and 3.0 mg/kg, s.c.) the hypokinesia of these animals while inducing marked increases in control mice. Cabergoline (0.3 mg/kg, s.c.) and bromocriptine (3.0 mg/kg, s.c.) caused dose-specific elevations of locomotion in MPTP and control mice but suppressed activity at the highest doses. Quinpirole (0.2 mg/kg) and 7-hydroxydipropylaminotetralin (7-OH-DPAT; 300 nmole/kg) increased locomotion in hypokinesic MPTP-treated mice; in control mice, activity was elevated by quinpirole (0.2 and 0.7 mg/kg) and 7-OH-DPAT (100 and 300 nmole/kg), while higher doses suppressed activity. Neither SKF 38393 (1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol) nor FCE 23884 [4-(9,10-didehydro-6-methylergolin-8 beta-yl) methyl-piperazine-2,6-dione] affected locomotor activity. Apomorphine (0.3, 1.0 and 2.0 mg/kg), bromocriptine (3.0 mg/kg) and cabergoline (1.0 mg/kg) stimulated locomotion in sham-operated rats, and to a greater extent in the 6-OHDA-treated rats. Higher dose cabergoline (3.0 mg/kg) induced increased activity of similar extent in sham controls and 6-OHDA treated rats. Activity-enhancing effects of quinpirole (0.2, 0.7 and 2.1 mg/kg) in sham rats were attenuated in 6-OHDA treated rats. Both SKF 38393 (10 mg/kg) and FCE 23884 (0.3 and 1.0 mg/kg) induced locomotor activity increases in 6-OHDA, but not sham, rats. Finally, 7-OH-DPAT (1200 mg/kg) enhanced activity in 6-OHDA rats vs. shams. The effects of the DA agonists are discussed with regard to the putative antihypokinesic effects in MPTP mice and DA-receptor supersensitivity effects in neonatal 6-OHDA rats, pertaining to their more-or-less selective subreceptor profiles.

Cognitive effects of muscarinic M1 functional agonists in non-human primates and clinical trials.

The limited effect of AChE inhibitors and NMDA receptor antagonists for the treatment of the cognitive symptoms of Alzheimer's disease has prompted the search for new drugs that are capable not only of treating behavioral symptoms, but also of modifying the disease process. Considerable research efforts have been focused on orthosteric muscarinic M1 functional agonists during the past decade to address both these strategies. Part of this research has included the use of non-human primates as models of cognitive impairment to demonstrate preclinical efficacy. No M1 functional agonist has been successfully registered for the treatment of Alzheimer's disease, mostly because of mechanism-related adverse side effects and marginal cognitive effects. However, the M1 agonist xanomeline exhibited preclinical and clinical efficacy for the treatment of the negative and cognitive symptoms of schizophrenia. These results prompted renewed interest in repositioning compounds such as sabcomeline (Proximagen Group plc) for this indication, as well as developing allosteric muscarinic M1 ligands to improve efficacy while reducing side-effect-related attrition. This review discusses preclinical and clinical data from orthosteric M1 functional agonists, focusing on target validation in primate cognition studies, and provides recommendations for testing a new generation of M1 ligands and compounds with novel mechanisms of action.

Characterization of energy expenditure in rodents by indirect calorimetry.

The need for treatment of obesity and obesity-related diseases, such as type 2 diabetes, has been intensified by the epidemic rise of obesity. Recent advances make possible continuous monitoring of metabolically relevant functions in animals to identify novel thermogenic and anorectic compounds. This unit describes non-invasive in vivo calorimetric assessment of energy expenditure using measurements of oxygen consumption and carbon dioxide production, complemented by telemetric monitoring of body core temperature and locomotor activity in mice and rats. Reference compounds are used to illustrate the determination of substance-specific parameters, such as the dose that produces the half-maximal effect (ED(50)), the maximal effect, as well as the time of onset and duration of compound action. Indirect calorimetry performed at different temperatures provides information on several other well-defined parameters, including resting metabolic rate, basal metabolic rate, lower critical temperature, temperature sensitivity, defended body temperature, and respiratory quotient.

Measurement and characterization of energy expenditure as a tool in the development of drugs for metabolic diseases, such as obesity and diabetes.

The need for treatment of obesity and obesity-related diseases, such as type 2 diabetes, has been intensified by the epidemic rise of obesity. Recent advances make possible continuous monitoring of metabolically relevant functions in animals to identify novel thermogenic and anorectic compounds. This unit describes non-invasive in vivo calorimetric assessment of energy expenditure using measurements of oxygen consumption and carbon dioxide production, complemented by telemetric monitoring of body core temperature and locomotor activity in mice and rats. Reference compounds are used to illustrate the determination of substance-specific parameters, such as the dose that produces the half-maximal effect (ED(50)), the maximal effect, as well as the time of onset and duration of compound action. Indirect calorimetry performed at different temperatures provides information on several other well-defined parameters, including resting metabolic rate, basal metabolic rate, lower critical temperature, temperature sensitivity, defended body temperature, and respiratory quotient.

Measurement and characterization of energy intake in the mouse.

Because of the dramatic increase in obesity and related conditions, such as type 2 diabetes, efforts have intensified to develop medications to assist in losing weight or in minimizing weight gain. To this end, methods that allow for the continuous monitoring of metabolically relevant functions in laboratory animals have been developed to help identify novel anorectic and thermogenic agents. Described in this unit is an in vivo procedure for simultaneous recording of feeding, drinking, and motor activity in mice. Data obtained using reference compounds are presented to illustrate how results are calculated, including the minimum effective dose and the dose producing a half-maximal effect (ED(50)), as well as the time of onset and duration of action. Information derived from this procedure reveals the specificity of an anorectic effect, which, when combined with parameters of meal patterns, allows for inferences to be made about the effects of test compounds on satiety and hunger.