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INTRODUCTION: Management of pain is a component of 80% of all emergency department (ED) visits, and intravenous (IV) opioids are most commonly used to treat moderate to severe pain. Since the dose of stock vials is rarely purchased based on provider ordering patterns, there is often a discrepancy between ordered doses and the dose of the stock vial, leading to waste. Here, waste is defined as the difference between the dose of the stock vials used to fill an order and the ordered dose. Drug waste is problematic as it increases the chance of administering the incorrect dose, it is a source of lost revenue, and in the context of opioids, it increases the opportunity for drug diversion. In this study, we sought to utilize real-world data to describe the magnitude of morphine and hydromorphone waste in the studied EDs. We also applied scenario analyses based on provider ordering patterns to simulate the effects of cost versus opioid waste minimization when making purchasing decisions for the dose of stock vial of each opioid. METHODS: This was an observational analysis of IV morphine and hydromorphone orders across three EDs within a health care system between December 1, 2014 and November 30, 2015. In the primary analysis we measured total waste and cost of all ordered hydromorphone and morphine, and we created logistic regression models for each opioid to estimate the odds that a given ordered dose would create waste. In the secondary scenario analysis we determined the total waste created and total cost to satisfy all written orders for both opioids with respect to prioritizing minimizing waste versus cost. RESULTS: Among a total of 34,465 IV opioid orders, 7866 (35%) of morphine orders created 21,767 mg of waste, and 10,015 (85%) of hydromorphone orders created 11,689 mg of waste. Larger dose orders were associated with a smaller likelihood of waste in both morphine and hydromorphone due to the doses of stock vials available. In the waste optimization scenario, relative to the base scenario, total waste, which included waste from both morphine and hydromorphone, was reduced by 97% and cost was reduced by 11%. In the cost optimization scenario, cost was reduced by 28% but waste increased by 22%. CONCLUSION: As hospitals continue to seek strategies to reduce costs and mitigate the harms of opioid diversion amidst the opioid epidemic, this study shows that optimizing the dose of the stock vial to minimize waste using provider ordering patterns, could mitigate risk while also reducing cost. Limitations included the use of data from EDs within a single health system, drug shortages that affected stock vial availability, and finally, the actual cost of stock vials, used for cost calculations, can differ based on a variety of factors.
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Analgésicos Opioides , Hidromorfona , Humanos , Analgésicos Opioides/uso terapêutico , Hidromorfona/uso terapêutico , Desvio de Medicamentos sob Prescrição , Morfina/uso terapêutico , Dor/tratamento farmacológico , Serviço Hospitalar de EmergênciaRESUMO
On the evening of June 23, 2016, a white powder advertised as cocaine was purchased off the streets from multiple sources and used by an unknown number of persons in New Haven, Connecticut. During a period of less than 8 hours, 12 patients were brought to the emergency department (ED) at Yale New Haven Hospital, experiencing signs and symptoms consistent with opioid overdose. The route of intoxication was not known, but presumed to be insufflation ("snorting") in most cases. Some patients required doses of the opioid antidote naloxone exceeding 4 mg (usual initial dose = 0.1-0.2 mg intravenously), and several patients who were alert after receiving naloxone subsequently developed respiratory failure. Nine patients were admitted to the hospital, including four to the intensive care unit (ICU); three required endotracheal intubation, and one required continuous naloxone infusion. Three patients died. The white powder was determined to be fentanyl, a drug 50 times more potent than heroin, and it included trace amounts of cocaine. The episode triggered rapid notification of public health and law enforcement agencies, interviews of patients and their family members to trace and limit further use or distribution of the fentanyl, immediate naloxone resupply and augmentation for emergency medical services (EMS) crews, public health alerts, and plans to accelerate naloxone distribution to opioid users and their friends and families. Effective communication and timely, coordinated, collaborative actions of community partners reduced the harm caused by this event and prevented potential subsequent episodes.
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Overdose de Drogas/diagnóstico , Fentanila/intoxicação , Adulto , Idoso , Connecticut , Overdose de Drogas/terapia , Serviço Hospitalar de Emergência , Evolução Fatal , Feminino , Fentanila/sangue , Fentanila/urina , Humanos , Masculino , Pessoa de Meia-Idade , Naloxona/uso terapêuticoRESUMO
Cyclic nucleotides are important signaling molecules that play many critical physiological roles including controlling cell fate and development, regulation of metabolic processes, and responding to changes in the environment. Cyclic nucleotides are also pivotal regulators in immune signaling, orchestrating intricate processes that maintain homeostasis and defend against pathogenic threats. This review provides a comprehensive examination of the pharmacological potential of cyclic nucleotide signaling pathways within the realm of immunity. Beginning with an overview of the fundamental roles of cAMP and cGMP as ubiquitous second messengers, this review delves into the complexities of their involvement in immune responses. Special attention is given to the challenges associated with modulating these signaling pathways for therapeutic purposes, emphasizing the necessity for achieving cell-type specificity to avert unintended consequences. A major focus of the review is on the recent paradigm-shifting discoveries regarding specialized cyclic nucleotide signals in the innate immune system, notably the cGAS-STING pathway. The significance of cyclic dinucleotides, exemplified by 2'3'-cGAMP, in controlling immune responses against pathogens and cancer, is explored. The evolutionarily conserved nature of cyclic dinucleotides as antiviral agents, spanning across diverse organisms, underscores their potential as targets for innovative immunotherapies. Findings from the last several years have revealed a striking diversity of novel bacterial cyclic nucleotide second messengers which are involved in antiviral responses. Knowledge of the existence and precise identity of these molecules coupled with accurate descriptions of their associated immune defense pathways will be essential to the future development of novel antibacterial therapeutic strategies. The insights presented herein may help researchers navigate the evolving landscape of immunopharmacology as it pertains to cyclic nucleotides and point toward new avenues or lines of thinking about development of therapeutics against the pathways they regulate.
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Nucleotídeos Cíclicos , Transdução de Sinais , Humanos , Animais , Nucleotídeos Cíclicos/metabolismo , Imunidade Inata , AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Nucleotidiltransferases/metabolismo , Proteínas de Membrana/metabolismoRESUMO
Syntrophus aciditrophicus strain SB is a model syntroph that degrades benzoate and alicyclic acids. The structure of a putative 3-hydroxypimelyl-CoA dehydrogenase from S. aciditrophicus strain SB (SaHcd1) was resolved at 1.78â Å resolution. SaHcd1 contains sequence motifs and structural features that belong to the short-chain dehydrogenase/reductase (SDR) family of NADPH-dependent oxidoreductases. SaHcd1 is proposed to concomitantly reduce NAD+ or NADP+ to NADH or NADPH, respectively, while converting 3-hydroxypimelyl-CoA to 3-oxopimeyl-CoA. Further enzymatic studies are needed to confirm the function of SaHcd1.
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Deltaproteobacteria , NADP/metabolismo , Cristalografia por Raios X , Deltaproteobacteria/metabolismo , Oxirredutases/metabolismo , NAD/metabolismoAssuntos
Monóxido de Carbono/sangue , Incêndios , Cianeto de Hidrogênio/intoxicação , Hidroxocobalamina/administração & dosagem , Intoxicação/terapia , Lesão por Inalação de Fumaça/complicações , Antídotos/administração & dosagem , Análise Química do Sangue , Serviços Médicos de Emergência/métodos , Serviço Hospitalar de Emergência , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Intoxicação/etiologia , Intoxicação/fisiopatologia , Medição de Risco , Resultado do Tratamento , Sinais VitaisRESUMO
Bacterial manganese (Mn) oxidation is catalyzed by a diverse group of microbes and can affect the fate of other elements in the environment. Yet, we understand little about the enzymes that catalyze this reaction. The Mn oxidizing protein MopA, from Erythrobacter sp. strain SD-21, is a heme peroxidase capable of Mn(II) oxidation. Unlike Mn oxidizing multicopper oxidase enzymes, an understanding of MopA is very limited. Sequence analysis indicates that MopA contains an N-terminal heme peroxidase domain and a C-terminal calcium binding domain. Heterologous expression and nickel affinity chromatography purification of the N-terminal peroxidase domain (MopA-hp) from Erythrobacter sp. strain SD-21 led to partial purification. MopA-hp is a heme binding protein that requires heme, NAD+, and calcium (Ca2+) for activity. Mn oxidation is also stimulated by the presence of pyrroloquinoline quinone. MopA-hp has a K M for Mn(II) of 154 ± 46 µM and k cat = 1.6 min-1. Although oxygen requiring MopA-hp is homologous to peroxidases based on sequence, addition of hydrogen peroxide and hydrogen peroxide scavengers had little effect on Mn oxidation, suggesting this is not the oxidizing agent. These studies provide insight into the mechanism by which MopA oxidizes Mn.
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In microbial communities, bacterial populations are commonly controlled using indiscriminate, broad range antibiotics. There are few ways to target specific strains effectively without disrupting the entire microbiome and local environment. Here, we use conjugation, a natural DNA horizontal transfer process among bacterial species, to deliver an engineered CRISPR interference (CRISPRi) system for targeting specific genes in recipient Escherichia coli cells. We show that delivery of the CRISPRi system is successful and can specifically repress a reporter gene in recipient cells, thereby establishing a new tool for gene regulation across bacterial cells and potentially for bacterial population control.
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Sistemas CRISPR-Cas/genética , Conjugação Genética/genética , Engenharia Genética/métodos , Interferência de RNA , Escherichia coli/genética , Transferência Genética Horizontal , Modelos Genéticos , Biologia SintéticaRESUMO
OBJECTIVE: The objective of the present study was to describe the implementation of an organizational learning model and evaluate the effectiveness and usability of an application used to facilitate it in an ED setting. METHODS: This was an implementation case study and technology evaluation. The organizational learning model was implemented using an online Web 2.0 collaborative learning application developed by the investigating team. Online use was tracked over a 9-month period. At the end of the study period, a usability assessment was conducted as well as a semistructured interview of participants to assess perceptions of usefulness and effect on learning capacity in the ED. RESULTS: Over a period of 9 months, a total of 54 individual sites from 74 eligible staff members were created within a specific web domain. There were 251 registered users including users outside the ED, who accessed learning materials within these sites 7494 times. The majority of staff members interviewed agreed or strongly agreed that the collaborative learning application had improved learning capacity within this ED (88%, 95% CI 74-94%). CONCLUSION: We demonstrate the implementation of an organizational learning model based on independent online sites networking together within an organization. This appears to be both usable and acceptable to staff members working in a large ED as a means of knowledge management.
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Difusão de Inovações , Serviço Hospitalar de Emergência , Gestão do Conhecimento , Corpo Clínico Hospitalar/psicologia , Sistemas On-Line/organização & administração , Adulto , Austrália , Comportamento Cooperativo , Educação a Distância/métodos , Educação a Distância/organização & administração , Feminino , Humanos , Equipes de Administração Institucional , Entrevistas como Assunto , Masculino , Corpo Clínico Hospitalar/estatística & dados numéricos , Modelos Organizacionais , New South Wales , Sistemas On-Line/estatística & dados numéricos , Avaliação de Programas e Projetos de Saúde , Apoio Social , Inquéritos e Questionários , Revisão da Utilização de Recursos de Saúde/estatística & dados numéricosRESUMO
OBJECTIVE: The authors previously developed a dynamic and integrated electronic decision support system called ACAFE (Asthma Clinical Assessment Form and Electronic decision support). The objective of this present study was to evaluate the effectiveness of this system on asthma management and documentation in an ED. METHOD: Observational study using a pre- and post-intervention design, comparing patients managed using ACAFE after its implementation with historical controls. A systematic data abstraction process was used to compare patient records. RESULTS: A total of 50 patients were enrolled in the study group. These were compared with 50 historical controls. Use of ACAFE was associated with significantly higher rates of documentation of asthma severity (98% vs 18%, P < 0.01), as well as other clinically important variables, such as asthma precipitants, intensive care admission history and smoking history. ACAFE was also associated with significantly higher rate of asthma discharge plan documentation (76% vs 16%, P < 0.01), and this remained significant after adjustment for triage category and seniority of treating doctor in a regression model. CONCLUSION: The use of this decision support system in patients presenting to emergency with asthma was associated with improvements in clinical documentation and discharge management plans. Electronic decision support systems developed collaboratively with clinicians should play an important part of system-wide efforts to improve guideline adherence and compliance in ED.
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Asma/terapia , Protocolos Clínicos , Sistemas de Apoio a Decisões Clínicas/instrumentação , Documentação/normas , Serviço Hospitalar de Emergência/normas , Fidelidade a Diretrizes , Alta do Paciente/normas , Adolescente , Adulto , Feminino , Fidelidade a Diretrizes/estatística & dados numéricos , Guias como Assunto , Humanos , Modelos Logísticos , Masculino , New South Wales , Razão de Chances , Avaliação de Processos e Resultados em Cuidados de Saúde , Adulto JovemRESUMO
OBJECTIVES: To evaluate the effectiveness of an integrated and dynamic electronic decision support system for management of acute asthma in the ED. METHODS: A randomized trial was conducted comparing clinician performance using this electronic interface compared with paper documentation in a simulation scenario. The outcomes were documentation of asthma-related information and consultation times. RESULTS: Use of this electronic interface was associated with significantly higher rates of documentation in 7 out of 10 variables, including provision of written short-term asthma management plans. After adjustment for participant seniority, there was no significant difference in consultation times. CONCLUSION: In a simulation trial, use of this electronic interface was associated with improvements in clinical and discharge documentation. Further studies are required to test this prototype in clinical practice.
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Asma/terapia , Sistemas de Apoio a Decisões Clínicas , Medicina de Emergência/métodos , Serviço Hospitalar de Emergência , Adulto , Documentação/métodos , Feminino , Humanos , Masculino , Análise e Desempenho de Tarefas , Resultado do TratamentoRESUMO
A simple high performance liquid chromatography (HPLC) method was developed and validated for the determination of six phenolic compounds, five anthraquinones (rhein, aloe-emodin, emodin, chrysophanol and physcion) and a flavonoid (kaempferol), in root extracts from Cassia alata L. Solid-phase extraction, using C(18) cartridges, was used to remove interfering substances from the root extracts. The extracts were analyzed on a C(18) column using an isocratic mobile phase which consisted of acetonitrile, methanol, and 10mM aqueous ammonium acetate (25:55:20, v/v). Identification of the analytes was performed by use of standards and on-line mass spectrometric detection using atmospheric pressure chemical ionization. The concentration of the phenolic compounds in the root extracts was determined using HPLC with ultraviolet detection at 260nm. The limits of detection obtained for the anlytes were in the range of 0.23-4.61ppm. The overall R.S.D. precision values (intra- and inter-day) for the retention times and peak-areas were lower than 0.16 and 2.10%, respectively. In addition, the recovery of the developed method for the analysis of these phenolic compounds was determined, and ranged from 81.2+/-4.3 to 106+/-2%.