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1.
Transfusion ; 63(4): 755-762, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36752098

RESUMEN

BACKGROUND: Surgical transfusion has an outsized impact on hospital-based transfusion services, leading to blood product waste and unnecessary costs. The objective of this study was to design and implement a streamlined, reliable process for perioperative blood issue ordering and delivery to reduce waste. STUDY DESIGN AND METHODS: To address the high rates of surgical blood issue requests and red blood cell (RBC) unit waste at a large academic medical center, a failure modes and effects analysis was used to systematically examine perioperative blood management practices. Based on identified failure modes (e.g., miscommunication, knowledge gaps), a multi-component action plan was devised involving process changes, education, electronic clinical decision support, audit, and feedback. Changes in RBC unit issue requests, returns, waste, labor, and cost were measured pre- and post-intervention. RESULTS: The number of perioperative RBC unit issue requests decreased from 358 per month (SD 24) pre-intervention to 282 per month (SD 16) post-intervention (p < .001), resulting in an estimated savings of 8.9 h per month in blood bank staff labor. The issue-to-transfusion ratio decreased from 2.7 to 2.1 (p < .001). Perioperative RBC unit waste decreased from 4.5% of units issued pre-intervention to 0.8% of units issued post-intervention (p < .001), saving an estimated $148,543 in RBC unit acquisition costs and $546,093 in overhead costs per year. DISCUSSION: Our intervention, designed based on a structured failure modes analysis, achieved sustained reductions in perioperative RBC unit issue orders, returns, and waste, with associated benefits for blood conservation and transfusion program costs.


Asunto(s)
Transfusión de Eritrocitos , Análisis de Modo y Efecto de Fallas en la Atención de la Salud , Humanos , Transfusión Sanguínea , Bancos de Sangre , Eritrocitos
2.
Br J Anaesth ; 127(3): 386-395, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34243940

RESUMEN

BACKGROUND: Intraoperative EEG suppression duration has been associated with postoperative delirium and mortality. In a clinical trial testing anaesthesia titration to avoid EEG suppression, the intervention did not decrease the incidence of postoperative delirium, but was associated with reduced 30-day mortality. The present study evaluated whether the EEG-guided anaesthesia intervention was also associated with reduced 1-yr mortality. METHODS: This manuscript reports 1 yr follow-up of subjects from a single-centre RCT, including a post hoc secondary outcome (1-yr mortality) in addition to pre-specified secondary outcomes. The trial included subjects aged 60 yr or older undergoing surgery with general anaesthesia between January 2015 and May 2018. Patients were randomised to receive EEG-guided anaesthesia or usual care. The previously reported primary outcome was postoperative delirium. The outcome of the current study was all-cause 1-yr mortality. RESULTS: Of the 1232 subjects enrolled, 614 subjects were randomised to EEG-guided anaesthesia and 618 subjects to usual care. One-year mortality was 57/591 (9.6%) in the guided group and 62/601 (10.3%) in the usual-care group. No significant difference in mortality was observed (adjusted absolute risk difference, -0.7%; 99.5% confidence interval, -5.8% to 4.3%; P=0.68). CONCLUSIONS: An EEG-guided anaesthesia intervention aiming to decrease duration of EEG suppression during surgery did not significantly decrease 1-yr mortality. These findings, in the context of other studies, do not provide supportive evidence for EEG-guided anaesthesia to prevent intermediate term postoperative death. CLINICAL TRIAL REGISTRATION: NCT02241655.


Asunto(s)
Anestesia/mortalidad , Electroencefalografía , Monitorización Neurofisiológica Intraoperatoria , Complicaciones Posoperatorias/mortalidad , Accidentes por Caídas , Anciano , Anestesia/efectos adversos , Monitores de Conciencia , Delirio/etiología , Delirio/mortalidad , Electroencefalografía/instrumentación , Femenino , Humanos , Monitorización Neurofisiológica Intraoperatoria/instrumentación , Masculino , Persona de Mediana Edad , Missouri , Complicaciones Cognitivas Postoperatorias/etiología , Complicaciones Cognitivas Postoperatorias/mortalidad , Complicaciones Posoperatorias/etiología , Valor Predictivo de las Pruebas , Calidad de Vida , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento
3.
Diabetes Care ; 43(5): 1070-1076, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32108022

RESUMEN

OBJECTIVE: Suboptimal adherence to insulin treatment is a main issue in adolescents with type 1 diabetes. However, to date, there are no available data on adherence to adjunct noninsulin medications in this population. Our aim was to assess adherence to ACE inhibitors and statins and explore potential determinants in adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS: There were 443 adolescents with type 1 diabetes recruited into the Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT) and exposed to treatment with two oral drugs-an ACE inhibitor and a statin-as well as combinations of both or placebo for 2-4 years. Adherence was assessed every 3 months with the Medication Event Monitoring System (MEMS) and pill count. RESULTS: Median adherence during the trial was 80.2% (interquartile range 63.6-91.8) based on MEMS and 85.7% (72.4-92.9) for pill count. Adherence based on MEMS and pill count dropped from 92.9% and 96.3%, respectively, at the first visit to 76.3% and 79.0% at the end of the trial. The percentage of study participants with adherence ≥75% declined from 84% to 53%. A good correlation was found between adherence based on MEMS and pill count (r = 0.82, P < 0.001). Factors associated with adherence were age, glycemic control, and country. CONCLUSIONS: We report an overall good adherence to ACE inhibitors and statins during a clinical trial, although there was a clear decline in adherence over time. Older age and suboptimal glycemic control at baseline predicted lower adherence during the trial, and, predictably, reduced adherence was more prevalent in subjects who subsequently dropped out.


Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Cumplimiento de la Medicación/estadística & datos numéricos , Adolescente , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Australia/epidemiología , Canadá/epidemiología , Quimioterapia Adyuvante , Niño , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 1/metabolismo , Angiopatías Diabéticas/prevención & control , Método Doble Ciego , Quimioterapia Combinada , Femenino , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Insulina/uso terapéutico , Masculino , Reino Unido/epidemiología
4.
Anesthesiology ; 132(6): 1458-1468, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32032096

RESUMEN

BACKGROUND: Postoperative delirium is a common complication that hinders recovery after surgery. Intraoperative electroencephalogram suppression has been linked to postoperative delirium, but it is unknown if this relationship is causal or if electroencephalogram suppression is merely a marker of underlying cognitive abnormalities. The hypothesis of this study was that intraoperative electroencephalogram suppression mediates a nonzero portion of the effect between preoperative abnormal cognition and postoperative delirium. METHODS: This is a prespecified secondary analysis of the Electroencephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES) randomized trial, which enrolled patients age 60 yr or older undergoing surgery with general anesthesia at a single academic medical center between January 2015 and May 2018. Patients were randomized to electroencephalogram-guided anesthesia or usual care. Preoperative abnormal cognition was defined as a composite of previous delirium, Short Blessed Test cognitive score greater than 4 points, or Eight Item Interview to Differentiate Aging and Dementia score greater than 1 point. Duration of intraoperative electroencephalogram suppression was defined as number of minutes with suppression ratio greater than 1%. Postoperative delirium was detected via Confusion Assessment Method or chart review on postoperative days 1 to 5. RESULTS: Among 1,113 patients, 430 patients showed evidence of preoperative abnormal cognition. These patients had an increased incidence of postoperative delirium (151 of 430 [35%] vs.123 of 683 [18%], P < 0.001). Of this 17.2% total effect size (99.5% CI, 9.3 to 25.1%), an absolute 2.4% (99.5% CI, 0.6 to 4.8%) was an indirect effect mediated by electroencephalogram suppression, while an absolute 14.8% (99.5% CI, 7.2 to 22.5%) was a direct effect of preoperative abnormal cognition. Randomization to electroencephalogram-guided anesthesia did not change the mediated effect size (P = 0.078 for moderation). CONCLUSIONS: A small portion of the total effect of preoperative abnormal cognition on postoperative delirium was mediated by electroencephalogram suppression. Study precision was too low to determine if the intervention changed the mediated effect.


Asunto(s)
Disfunción Cognitiva/complicaciones , Disfunción Cognitiva/fisiopatología , Electroencefalografía/estadística & datos numéricos , Delirio del Despertar/complicaciones , Delirio del Despertar/fisiopatología , Monitoreo Intraoperatorio/métodos , Anciano , Electroencefalografía/métodos , Femenino , Humanos , Masculino , Periodo Preoperatorio
5.
Anesth Analg ; 130(3): 777-786, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31880629

RESUMEN

BACKGROUND: Electroencephalographic (EEG) brain monitoring during general anesthesia provides information on hypnotic depth. We hypothesized that anesthesia clinicians could be trained rapidly to recognize typical EEG waveforms occurring with volatile-based general anesthesia. METHODS: This was a substudy of a trial testing the hypothesis that EEG-guided anesthesia prevents postoperative delirium. The intervention was a 35-minute training session, summarizing typical EEG changes with volatile-based anesthesia. Participants completed a preeducational test, underwent training, and completed a posteducational test. For each question, participants indicated whether the EEG was consistent with (1) wakefulness, (2) non-slow-wave anesthesia, (3) slow-wave anesthesia, or (4) burst suppression. They also indicated whether the processed EEG (pEEG) index was discordant with the EEG waveforms. Four clinicians, experienced in intraoperative EEG interpretation, independently evaluated the EEG waveforms, resolved disagreements, and provided reference answers. Ten questions were assessed in the preeducational test and 9 in the posteducational test. RESULTS: There were 71 participants; 13 had previous anesthetic-associated EEG interpretation training. After training, the 58 participants without prior training improved at identifying dominant EEG waveforms (median 60% with interquartile range [IQR], 50%-70% vs 78% with IQR, 67%-89%; difference: 18%; 95% confidence interval [CI], 8-27; P < .001). In contrast, there was no significant improvement following the training for the 13 participants who reported previous training (median 70% with IQR, 60%-80% vs 67% with IQR, 67%-78%; difference: -3%; 95% CI, -18 to 11; P = .88). The difference in the change between the pre- and posteducational session for the previously untrained versus previously trained was statistically significant (difference in medians: 21%; 95% CI, 2-28; P = .005). Clinicians without prior training also improved in identifying discordance between the pEEG index and the EEG waveform (median 60% with IQR, 40%-60% vs median 100% with IQR, 75%-100%; difference: 40%; 95% CI, 30-50; P < .001). Clinicians with prior training showed no significant improvement (median 60% with IQR, 60%-80% vs 75% with IQR, 75%-100%; difference: 15%; 95% CI, -16 to 46; P = .16). Regarding the identification of discordance, the difference in the change between the pre- and posteducational session for the previously untrained versus previously trained was statistically significant (difference in medians: 25%; 95% CI, 5-45; P = .012). CONCLUSIONS: A brief training session was associated with improvements in clinicians without prior EEG training in (1) identifying EEG waveforms corresponding to different hypnotic depths and (2) recognizing when the hypnotic depth suggested by the EEG was discordant with the pEEG index.


Asunto(s)
Anestesia por Inhalación , Anestesiólogos/educación , Anestesiología/educación , Estado de Conciencia/efectos de los fármacos , Educación Médica Continua , Electroencefalografía , Capacitación en Servicio , Monitorización Neurofisiológica Intraoperatoria/métodos , Anestesiólogos/psicología , Competencia Clínica , Evaluación Educacional , Escolaridad , Conocimientos, Actitudes y Práctica en Salud , Humanos , Variaciones Dependientes del Observador , Ensayos Clínicos Pragmáticos como Asunto , Valor Predictivo de las Pruebas , Evaluación de Programas y Proyectos de Salud , Reconocimiento en Psicología
6.
J Cardiothorac Vasc Anesth ; 33(11): 3163-3175, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30867107

RESUMEN

With advances in modern day imaging techniques for the aorta, there has been an increasing incidence of vascular diseases involving the aortic arch. Historically, the only treatment option for arch disease has been open arch replacement under circulatory arrest conditions with or without selective cerebral perfusion. However, this open procedure has significant morbidity and mortality, especially in elderly patients with multiple comorbidities. To potentially mitigate the risks associated with open replacement, endovascular arch repair has gained momentum as an alternative treatment option. Currently, aortic arch stenting is being trialed in multiple international medical centers across Europe and the United States. The outcomes data available thus far are promising, which suggest that there likely will be an increase in patients being referred for aortic arch stenting procedures in the future. In this emerging technology review, multiple aspects of the aortic arch stenting procedure are discussed including the currently available endovascular arch devices, the unique surgical and anesthetic considerations for arch stent implantation, and the early outcomes data published to date.


Asunto(s)
Anestésicos/uso terapéutico , Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/cirugía , Disección Aórtica/cirugía , Implantación de Prótesis Vascular/métodos , Procedimientos Endovasculares/métodos , Stents , Humanos , Diseño de Prótesis
7.
JAMA ; 321(5): 473-483, 2019 02 05.
Artículo en Inglés | MEDLINE | ID: mdl-30721296

RESUMEN

Importance: Intraoperative electroencephalogram (EEG) waveform suppression, often suggesting excessive general anesthesia, has been associated with postoperative delirium. Objective: To assess whether EEG-guided anesthetic administration decreases the incidence of postoperative delirium. Design, Setting, and Participants: Randomized clinical trial of 1232 adults aged 60 years and older undergoing major surgery and receiving general anesthesia at Barnes-Jewish Hospital in St Louis. Recruitment was from January 2015 to May 2018, with follow-up until July 2018. Interventions: Patients were randomized 1:1 (stratified by cardiac vs noncardiac surgery and positive vs negative recent fall history) to receive EEG-guided anesthetic administration (n = 614) or usual anesthetic care (n = 618). Main Outcomes and Measures: The primary outcome was incident delirium during postoperative days 1 through 5. Intraoperative measures included anesthetic concentration, EEG suppression, and hypotension. Adverse events included undesirable intraoperative movement, intraoperative awareness with recall, postoperative nausea and vomiting, medical complications, and death. Results: Of the 1232 randomized patients (median age, 69 years [range, 60 to 95]; 563 women [45.7%]), 1213 (98.5%) were assessed for the primary outcome. Delirium during postoperative days 1 to 5 occurred in 157 of 604 patients (26.0%) in the guided group and 140 of 609 patients (23.0%) in the usual care group (difference, 3.0% [95% CI, -2.0% to 8.0%]; P = .22). Median end-tidal volatile anesthetic concentration was significantly lower in the guided group than the usual care group (0.69 vs 0.80 minimum alveolar concentration; difference, -0.11 [95% CI, -0.13 to -0.10), and median cumulative time with EEG suppression was significantly less (7 vs 13 minutes; difference, -6.0 [95% CI, -9.9 to -2.1]). There was no significant difference between groups in the median cumulative time with mean arterial pressure below 60 mm Hg (7 vs 7 minutes; difference, 0.0 [95% CI, -1.7 to 1.7]). Undesirable movement occurred in 137 patients (22.3%) in the guided and 95 (15.4%) in the usual care group. No patients reported intraoperative awareness. Postoperative nausea and vomiting was reported in 48 patients (7.8%) in the guided and 55 patients (8.9%) in the usual care group. Serious adverse events were reported in 124 patients (20.2%) in the guided and 130 (21.0%) in the usual care group. Within 30 days of surgery, 4 patients (0.65%) in the guided group and 19 (3.07%) in the usual care group died. Conclusions and Relevance: Among older adults undergoing major surgery, EEG-guided anesthetic administration, compared with usual care, did not decrease the incidence of postoperative delirium. This finding does not support the use of EEG-guided anesthetic administration for this indication. Trial Registration: ClinicalTrials.gov Identifier: NCT02241655.


Asunto(s)
Anestésicos Generales/administración & dosificación , Electroencefalografía , Delirio del Despertar/prevención & control , Monitoreo Intraoperatorio/métodos , Anciano , Anciano de 80 o más Años , Algoritmos , Anestesia General/efectos adversos , Anestésicos Generales/efectos adversos , Cardiotónicos/uso terapéutico , Delirio del Despertar/epidemiología , Femenino , Humanos , Hipotensión/inducido químicamente , Hipotensión/tratamiento farmacológico , Incidencia , Complicaciones Intraoperatorias/inducido químicamente , Masculino , Persona de Mediana Edad , Fenilefrina/uso terapéutico , Náusea y Vómito Posoperatorios , Procedimientos Quirúrgicos Operativos/efectos adversos , Procedimientos Quirúrgicos Operativos/mortalidad
10.
Curr Top Med Chem ; 9(8): 724-37, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19689377

RESUMEN

Interleukin-1 receptor-associated kinases (IRAKs) are key components in the signal transduction pathways utilized by interleukin-1 receptor (IL-1R), interleukin-18 receptor (IL-18R), and Toll-like receptors (TLRs). Out of four members in the mammalian IRAK family, IRAK-4 is considered to be the "master IRAK", the only family member indispensable for IL-1R/TLR signaling. In humans, mutations resulting in IRAK-4 deficiency have been linked to susceptibility to bacterial infections, especially recurrent pyogenic bacterial infections. Furthermore, knock-in experiments by several groups have clearly demonstrated that IRAK-4 requires its kinase activity for its function. Given the critical role of IRAK-4 in inflammatory processes, modulation of IRAK-4 kinase activity presents an attractive therapeutic approach for the treatment of immune and inflammatory diseases. The recent success in the determination of the 3-dimensional structure of the IRAK-4 kinase domain in complex with inhibitors has facilitated the understanding of the mechanistic role of IRAK-4 in immunity and inflammation as well as the development of specific IRAK-4 kinase inhibitors. In this article, we review the biological function of IRAK-4, the structural characteristics of the kinase domain, and the development of small molecule inhibitors targeting the kinase activity. We also review the key pharmacophores required for several classes of inhibitors as well as important features for optimal protein/inhibitor interactions. Lastly, we summarize how these insights can be translated into strategies to develop potent IRAK-4 inhibitors with desired properties as new anti-inflammatory therapeutic agents.


Asunto(s)
Antiinflamatorios/farmacología , Inflamación/tratamiento farmacológico , Quinasas Asociadas a Receptores de Interleucina-1/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/farmacología , Animales , Antiinflamatorios/uso terapéutico , Diseño de Fármacos , Humanos , Quinasas Asociadas a Receptores de Interleucina-1/química , Quinasas Asociadas a Receptores de Interleucina-1/metabolismo , Conformación Proteica , Inhibidores de Proteínas Quinasas/uso terapéutico
11.
Bioconjug Chem ; 19(9): 1775-84, 2008 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-18763820

RESUMEN

Salicylanilides were found as selective inhibitors of interleukin-12p40 production in stimulated dendritic cells. The conversion of one of these bioactive salicylanilides into a comparably bioactive, chemically labeled derivative was achieved using a facile and systematic functional group derivatization strategy. This resulted in a tool reagent that was then employed in an affinity chromatography approach that resulted in the identification of the protein 14-3-3zeta as having selective affinity for the chromatography matrix that was derivatized with a salicylanilide that inhibited IL-12p40 production.


Asunto(s)
Proteínas 14-3-3/química , Marcadores de Afinidad/química , Subunidad p40 de la Interleucina-12/antagonistas & inhibidores , Salicilanilidas/química , Animales , Línea Celular , Cromatografía de Afinidad , Células Dendríticas , Subunidad p40 de la Interleucina-12/biosíntesis , Ratones , Ratas
12.
Bioorg Med Chem ; 16(18): 8760-4, 2008 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-18715785

RESUMEN

Interleukin (IL)-12p40, a subunit component of both IL-12 and IL-23, is being widely studied for its role in inflammatory disease. As part of an effort to profile cellular signaling pathways across different cell types, we report salicylanilide inhibitors of IL-12p40 production in stimulated dendritic cells. Based on a hypothesis that a desirable therapeutic profile is one that could block IL-12p40 but not IL-6 production, we engaged in directed analoging. This resulted in salicylanilides with similar IL-12p40 related potency but enhanced selectivity relative to IL-6 production.


Asunto(s)
Antiinflamatorios/farmacología , Membrana Celular/efectos de los fármacos , Subunidad p40 de la Interleucina-12/antagonistas & inhibidores , Salicilanilidas/farmacología , Transducción de Señal/efectos de los fármacos , Animales , Antiinflamatorios/química , Bioensayo , Membrana Celular/metabolismo , Células Cultivadas , Células Dendríticas , Subunidad p40 de la Interleucina-12/metabolismo , Interleucina-23/antagonistas & inhibidores , Interleucina-23/metabolismo , Interleucina-6/antagonistas & inhibidores , Interleucina-6/metabolismo , Ratones , Salicilanilidas/química , Transducción de Señal/fisiología
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