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BACKGROUND: Mutations present in emerging SARS-CoV-2 variants permit evasion of neutralization with prototype vaccines. A novel Omicron BA.1 subvariant-specific vaccine (NVX-CoV2515) was tested alone or as a bivalent preparation with the prototype vaccine (NVX-CoV2373) to assess antibody responses to SARS-CoV-2. METHODS: Participants aged 18 to 64 years immunized with 3 doses of prototype mRNA vaccines were randomized 1:1:1 to receive a single dose of NVX-CoV2515, NVX-CoV2373, or the bivalent mixture in a phase 3 study investigating heterologous boosting with SARS-CoV-2 recombinant spike protein vaccines. Immunogenicity was measured 14 and 28 days after vaccination for the SARS-CoV-2 Omicron BA.1 sublineage and ancestral strain. Safety profiles of vaccines were assessed. RESULTS: Of participants who received trial vaccine (N = 829), those administered NVX-CoV2515 (n = 286) demonstrated a superior neutralizing antibody response to BA.1 vs NVX-CoV2373 (n = 274) at day 14 (geometric mean titer ratio, 1.6; 95% CI, 1.33-2.03). Seroresponse rates were 73.4% (91/124; 95% CI, 64.7-80.9) for NVX-CoV2515 vs 50.9% (59/116; 95% CI, 41.4-60.3) for NVX-CoV2373. All formulations were similarly well tolerated. CONCLUSIONS: NVX-CoV2515 elicited a superior neutralizing antibody response against the Omicron BA.1 subvariant as compared with NVX-CoV2373 when administered as a fourth dose. Safety data were consistent with the established safety profile of NVX-CoV2373. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov (NCT05372588).
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Inmunización Secundaria , Inmunogenicidad Vacunal , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Humanos , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Vacunas contra la COVID-19/efectos adversos , Adulto , SARS-CoV-2/inmunología , SARS-CoV-2/genética , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/genética , Masculino , Femenino , COVID-19/prevención & control , COVID-19/inmunología , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Adulto Joven , Persona de Mediana Edad , Adolescente , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/efectos adversosRESUMEN
Access to high-quality food is critical for long-distance migrants to provide energy for migration and arrival at breeding grounds in good condition. We studied effects of changing abundance and availability of a marine food, common eelgrass (Zostera marina L.), on an arctic-breeding, migratory goose, black brant (Brant bernicla nigricans Lawrence 1846), at a key non-breeding site, Bahía San Quintín, Mexico. Eelgrass, the primary food of brant, is consumed when exposed by the tide or within reach from the water's surface. Using an individual-based model, we predicted effects of observed changes (1991-2013) in parameters influencing food abundance and availability: eelgrass biomass (abundance), eelgrass shoot length (availability, as longer shoots more within reach), brant population size (availability, as competition greater with more birds), and sea level (availability, as less food within reach when sea level higher). The model predicted that the ability to gain enough energy to migrate was most strongly influenced by eelgrass biomass (threshold January biomass for migration = 60 g m-2 dry mass). Conversely, annual variation in population size (except for 1998), was relatively low, and variation in eelgrass shoot length and sea level were not strongly related to ability to migrate. We used observed data on brant body mass at Bahía San Quintín and annual survival to test for effects of eelgrass biomass in the real system. The lowest observed values of body mass and survival were in years when biomass was below 60 g m-2, although in some years of low biomass body mass and/or survival was higher. This suggests that the real birds may have some capacity to compensate to meet their energy demands when eelgrass biomass is low. We discuss consequences for brant population trends and conservation.
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BACKGROUND: Mutations present in emerging SARS-CoV-2 variants permit evasion of neutralization with prototype vaccines. A novel Omicron BA.1 subvariant-specific vaccine (NVX-CoV2515) was tested alone, or as a bivalent preparation in combination with the prototype vaccine (NVX-CoV2373), to assess antibody responses to SARS-CoV-2. METHODS: Participants aged 18 to 64 years immunized with 3 doses of prototype mRNA vaccines were randomized 1:1:1 to receive a single dose of NVX-CoV2515, NVX-CoV2373, or bivalent mixture in a phase 3 study investigating heterologous boosting with SARS-CoV-2 recombinant spike protein vaccines. Immunogenicity was measured 14 and 28 days after vaccination for the SARS-CoV-2 Omicron BA.1 sublineage and ancestral strain. Safety profiles of vaccines were assessed. RESULTS: Of participants who received trial vaccine (N = 829), those administered NVX-CoV2515 (n = 286) demonstrated superior neutralizing antibody response to BA.1 versus NVX-CoV2373 (n = 274) at Day 14 (geometric mean titer ratio [95% CI]: 1.6 [1.33, 2.03]). Seroresponse rates [n/N; 95% CI] were 73.4% [91/124; 64.7, 80.9] for NVX-CoV2515 versus 50.9% [59/116; 41.4, 60.3] for NVX-CoV2373. All formulations were similarly well-tolerated. CONCLUSIONS: NVX-CoV2515 elicited a superior neutralizing antibody response against the Omicron BA.1 subvariant compared with NVX-CoV2373 when administered as a fourth dose. Safety data were consistent with the established safety profile of NVX-CoV2373.
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BACKGROUND: The recombinant protein-based vaccine, NVX-CoV2373, demonstrated 89.7% efficacy against coronavirus disease 2019 (COVID-19) in a phase 3, randomized, observer-blinded, placebo-controlled trial in the United Kingdom. The protocol was amended to include a blinded crossover. Data to the end of the placebo-controlled phase are reported. METHODS: Adults aged 18-84 years received 2 doses of NVX-CoV2373 or placebo (1:1) and were monitored for virologically confirmed mild, moderate, or severe COVID-19 (onset from 7 days after second vaccination). Participants who developed immunoglobulin G (IgG) against nucleocapsid protein but did not show symptomatic COVID-19 were considered asymptomatic. Secondary outcomes included anti-spike (S) IgG responses, wild-type virus neutralization, and T-cell responses. RESULTS: Of 15 185 participants, 13 989 remained in the per-protocol efficacy population (6989 NVX-CoV2373, 7000 placebo). At a maximum of 7.5 months (median, 4.5) postvaccination, there were 24 cases of COVID-19 among NVX-CoV2373 recipients and 134 cases among placebo recipients, a vaccine efficacy of 82.7% (95% confidence interval [CI], 73.3%-88.8%). Vaccine efficacy was 100% (95% CI, 17.9%-100.0%) against severe disease and 76.3% (95% CI, 57.4%-86.8%) against asymptomatic disease. High anti-S and neutralization responses to vaccination were evident, together with S-protein-specific induction of interferon-γ secretion in peripheral blood T cells. Incidence of serious adverse events and adverse events of special interest were similar between groups. CONCLUSIONS: A 2-dose regimen of NVX-CoV2373 conferred a high level of ongoing protection against asymptomatic, symptomatic, and severe COVID-19 through >6 months postvaccination. A gradual decrease of protection suggests that a booster may be indicated. CLINICAL TRIALS REGISTRATION: EudraCT, 2020-004123-16.
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Vacunas contra la COVID-19 , COVID-19 , Adulto , Humanos , Vacunas contra la COVID-19/efectos adversos , COVID-19/prevención & control , SARS-CoV-2 , Vacunas Sintéticas/efectos adversos , Inmunoglobulina G , Inmunogenicidad Vacunal , Método Doble Ciego , Anticuerpos AntiviralesRESUMEN
BACKGROUND: The safety and immunogenicity profile of COVID-19 vaccines when administered concomitantly with seasonal influenza vaccines have not yet been reported. We therefore aimed to report the results of a substudy within a phase 3 UK trial, by evaluating the safety, immunogenicity, and efficacy of NVX-CoV2373 when co-administered with licensed seasonal influenza vaccines. METHODS: We did a planned exploratory substudy as part of the randomised, observer-blinded, placebo-controlled, phase 3 trial of the safety and efficacy of the COVID-19 vaccine (NVX-CoV2373) by co-administrating the influenza vaccine at four study hospitals in the UK. Approximately, the first 400 participants meeting the main study entry criteria-with no contraindications to influenza vaccination-were invited to join the substudy. Participants of the main study were randomly assigned (1:1) to receive two intramuscular injections of either NVX-CoV2373 (5 µg) or placebo (normal saline) 21 days apart; participants enrolled into the substudy were co-vaccinated with a single (0·5 mL) intramuscular, age-appropriate (quadrivalent influenza cell-based vaccine [Flucelvax Quadrivalent; Seqirus UK, Maidenhead] for those aged 18-64 years and adjuvanted trivalent influenza vaccine [Fluad; Seqirus UK, Maidenhead] for those ≥65 years), licensed, influenza vaccine on the opposite deltoid to that of the first study vaccine dose or placebo. The influenza vaccine was administered in an open-label manner and at the same time as the first study injection. Reactogenicity was evaluated via an electronic diary for 7 days after vaccination in addition to monitoring for unsolicited adverse events, medically attended adverse events, and serious adverse events. Immunogenicity was assessed with influenza haemagglutination inhibition and SARS-CoV-2 anti-spike protein IgG assays. Vaccine efficacy against PCR-confirmed, symptomatic COVID-19 was assessed in participants who were seronegative at baseline, received both doses of study vaccine or placebo, had no major protocol deviations affecting the primary endpoint, and had no confirmed cases of symptomatic COVID-19 from the first dose until 6 days after the second dose (per-protocol efficacy population). Immunogenicity was assessed in participants who received scheduled two doses of study vaccine, had a baseline sample and at least one post-vaccination sample, and had no major protocol violations before unmasking (per-protocol immunogenicity population). Reactogenicity was analysed in all participants who received at least one dose of NVX-CoV2373 or placebo and had data collected for reactogenicity events. Safety was analysed in all participants who received at least one dose of NVX-CoV2373 or placebo. Comparisons were made between participants of the substudy and the main study (who were not co-vaccinated for influenza). This study is registered with ClinicalTrials.gov, number NCT04583995. FINDINGS: Between Sept 28, 2020, and Nov 28, 2020, a total of 15 187 participants were randomised into the main phase 3 trial, of whom 15 139 received treatment (7569 received dose one of NVX-CoV2373 and 7570 received dose one of placebo). 431 participants were co-vaccinated with a seasonal influenza vaccine in the substudy (217 received NVX-CoV2373 plus the influenza vaccine and 214 received placebo plus the influenza vaccine). In general, the substudy participants were younger, more racially diverse, and had fewer comorbid conditions than those in the main study. Reactogenicity events were more common in the co-administration group than in the NVX-CoV2373 alone group: tenderness (113 [64·9%] of 174 vs 592 [53·3%] of 1111) or pain (69 [39·7%] vs 325 [29·3%]) at injection site, fatigue (48 [27·7%] vs 215 [19·4%]), and muscle pain (49 [28·3%] vs 237 [21·4%]). Incidences of unsolicited adverse events, treatment-related medically attended adverse events, and serious adverse events were low and balanced between the co-administration group and the NVX-CoV2373 alone group. No episodes of anaphylaxis or deaths were reported within the substudy. Co-administration resulted in no change to influenza vaccine immune response although a reduction in antibody responses to the NVX-CoV2373 vaccine was noted. NVX-CoV2373 vaccine efficacy in the substudy (ie, participants aged 18 to <65 years) was 87·5% (95% CI -0·2 to 98·4) and in the main study was 89·8% (95% CI 79·7-95·5). INTERPRETATION: To our knowledge, this substudy is the first to show the safety, immunogenicity, and efficacy profile of a COVID-19 vaccine when co-administered with seasonal influenza vaccines. Our results suggest concomitant vaccination might be a viable immunisation strategy. FUNDING: Novavax.
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COVID-19 , Vacunas contra la Influenza , Adolescente , Adulto , Anciano , Vacunas contra la COVID-19 , Método Doble Ciego , Humanos , Inmunogenicidad Vacunal , Vacunas contra la Influenza/efectos adversos , Persona de Mediana Edad , SARS-CoV-2 , Estaciones del Año , Adulto JovenAsunto(s)
Dermatitis Exfoliativa/etiología , Inmunodeficiencia Combinada Grave/diagnóstico , Piel/patología , Biopsia , Dermatitis Exfoliativa/patología , Diagnóstico Diferencial , Humanos , Recién Nacido , Masculino , Inmunodeficiencia Combinada Grave/complicaciones , Inmunodeficiencia Combinada Grave/patologíaRESUMEN
BACKGROUND: Determining diagnostic thresholds for cardiac troponin assays is key to interpreting their clinical performance. We describe the calculation of 99th percentile upper reference limits (URLs) for the Elecsys® Troponin T Gen 5 (TnT Gen 5) assay. METHODS: Plasma and serum samples from healthy US participants were prospectively evaluated using TnT Gen 5 Short Turn Around Time and 18-min assays on cobas e 411 and cobas e 601 analyzers (Roche Diagnostics); with, up to 8 TnT Gen 5 results per participant. RESULTS: A total of 10,402 TnT Gen 5 results from 1301 participants were included (50.4% female). Across 9 calculation methods, overall 99th percentile URL was 19.2 ng/l (females, 13.5-13.6 ng/l; males, 21.4-22.2 ng/l). Across different sample/assay/analyzer combinations, overall 99th percentile URLs ranged from 18.4-20.2 ng/l. Median TnT Gen 5 results increased with age, were higher in males, and ranged from 3.0-3.7 ng/l across races/ethnicities and from 3.0-3.6 ng/l across body mass index (BMI) classes. Applying additional exclusion criteria (N-terminal pro-brain natriuretic peptide, BMI and estimated glomerular filtration rate) resulted in lower 99th percentile URLs (overall, 16.9 ng/l; females, 11.8 ng/l; males, 18.5 ng/l). CONCLUSION: Our findings facilitate the interpretation of TnT Gen 5 results in US clinical practice.
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Bioensayo , Troponina T , Femenino , Humanos , Masculino , Grupos Raciales , Valores de Referencia , Estados UnidosRESUMEN
BACKGROUND: Contemporary reconsideration of diagnostic N-terminal pro-B-type natriuretic peptide (NT-proBNP) cutoffs for diagnosis of heart failure (HF) is needed. OBJECTIVES: This study sought to evaluate the diagnostic performance of NT-proBNP for acute HF in patients with dyspnea in the emergency department (ED) setting. METHODS: Dyspneic patients presenting to 19 EDs in North America were enrolled and had blood drawn for subsequent NT-proBNP measurement. Primary endpoints were positive predictive values of age-stratified cutoffs (450, 900, and 1,800 pg/ml) for diagnosis of acute HF and negative predictive value of the rule-out cutoff to exclude acute HF. Secondary endpoints included sensitivity, specificity, and positive (+) and negative (-) likelihood ratios (LRs) for acute HF. RESULTS: Of 1,461 subjects, 277 (19%) were adjudicated as having acute HF. The area under the receiver-operating characteristic curve for diagnosis of acute HF was 0.91 (95% confidence interval [CI]: 0.90 to 0.93; p < 0.001). Sensitivity for age stratified cutoffs of 450, 900, and 1,800 pg/ml was 85.7%, 79.3%, and 75.9%, respectively; specificity was 93.9%, 84.0%, and 75.0%, respectively. Positive predictive values were 53.6%, 58.4%, and 62.0%, respectively. Overall LR+ across age-dependent cutoffs was 5.99 (95% CI: 5.05 to 6.93); individual LR+ for age-dependent cutoffs was 14.08, 4.95, and 3.03, respectively. The sensitivity and negative predictive value for the rule-out cutoff of 300 pg/ml were 93.9% and 98.0%, respectively; LR- was 0.09 (95% CI: 0.05 to 0.13). CONCLUSIONS: In acutely dyspneic patients seen in the ED setting, age-stratified NT-proBNP cutpoints may aid in the diagnosis of acute HF. An NT-proBNP <300 pg/ml strongly excludes the presence of acute HF.
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Disnea , Insuficiencia Cardíaca , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Factores de Edad , Anciano , Biomarcadores/sangre , Disnea/sangre , Disnea/etiología , Servicio de Urgencia en Hospital , Femenino , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Reproducibilidad de los Resultados , Medición de RiesgoRESUMEN
Acute pancreatitis is a well-recognised complication of hypertriglyceridaemia. High serum triglycerides may develop in the autosomal recessive disorder glycogen storage disease (GSD). Plasmapheresis has been effective in reducing triglyceride levels in pancreatitis secondary to other conditions but not previously described in GSD. We describe a 16-year-old male with type 1a GSD who presented with severe abdominal pain, tachycardia and tachypnoea. Abdominal computed tomography (CT) demonstrated acute pancreatitis. Serum triglycerides were 91.8 mM. Despite intravenous fluids and morphine sulphate, he remained seriously ill, and plasmapheresis was therefore started. After daily plasma exchange for 6 days, triglyceride levels dropped to 5 mM. This was associated with a rapid resolution of pancreatitis. Plasmapheresis is effective in rapidly reducing hypertriglyceridaemia from numerous causes, including glycogen storage disease, and may facilitate recovery from acute pancreatitis.
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The aim of this study was to determine the incidence of, and any changes in, usage patterns of the less-lethal forms of Use of Force (UoF) modalities--incapacitant spray, impact rounds, and Taser(R)--between 2007 and 2011 by English and Welsh police services. Additional information regarding the deployment and discharge of firearms was also sought. Two thousand Freedom of Information Act applications were made to 50 police services in England and Wales and related jurisdictions requesting the provision of: (a) the total number of deployments of incapacitant sprays, Taser(R), impact (baton) rounds, and armed response units (ARU); (b) the numbers and types of any resulting medical complications; and (c) the details of any local policies requiring assessment by a healthcare professional following a deployment. Responses were received from 47 police services, with only 10 of these supplying complete data. The remainder supplied incomplete data or refused to supply any data under s12 of the Freedom of Information Act (time and cost restrictions). From 2007 to 2011, the use of incapacitant sprays, Taser, and firearms have increased (incapacitant sprays deployed: 3496, 3976, 6911, 6679, 6853; Taser deployed: 499, 2659, 4560, 6943, 7203; Taser discharged: 15, 85, 161, 338, 461; firearms: 0, 7, 4, 19, 32). Baton rounds and ARU use showed greater variability over the same time period (baton rounds: 1007, 1327, 1123, 1382, 1278; ARUs: 11688, 13652, 13166, 13959, 12090). Only two services could provide details of medical consequences from use of incapacitant sprays, Taser, and baton rounds. No service could provide details of any related medical complications following use of firearms. Data collection and release are variable and inconsistent throughout English and Welsh police services and thus caution is needed in determining trends of UoF techniques. Deaths or injuries inflicted using UoF techniques result in much public scrutiny and the low level of data recorded in these cases is of concern. Common systems for recording use and adverse outcomes of UoF techniques are needed to inform the public and others who have concerns about such techniques.
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Aplicación de la Ley , Policia/tendencias , Armas , Heridas y Lesiones/prevención & control , Acceso a la Información , Electrochoque/efectos adversos , Electrochoque/tendencias , Inglaterra/epidemiología , Armas de Fuego , Humanos , Incidencia , Irritantes/efectos adversos , Restricción Física/efectos adversos , Factores de Tiempo , Gales/epidemiología , Heridas y Lesiones/epidemiologíaRESUMEN
The outcomes of acute myocardial infarction, trauma, and stroke have improved by implementing processes that provide early diagnosis and aggressive interventions at the most proximal point of disease presentation. A common feature in these conditions is the implementation of early intervention strategies. One decade ago, a similar approach to sepsis began when a prospective randomized trial compared early goal-directed therapy (EGDT) to standard care using specific criteria for the early identification of high risk patients with infection. The components of EGDT were derived from expert consensus opinion to produce a protocol to reverse the hemodynamic perturbations of hypovolemia, vasodysregulation, myocardial suppression and increased metabolic demands for patients with severe sepsis in the intensive care unit (ICU). However, EGDT was provided at the most proximal phase of disease presentation in the Emergency Department (ED). With EGDT, a reduction in mortality of over 16% was shown over standard care. Since the EGDT study was published a decade ago, significant emphasis worldwide has been placed on a comprehensive approach to the first 6 hours of sepsis management which is commonly referred to as the resuscitation bundle (RB). The RB consists of early diagnosis, risk stratification using lactate levels, hemodynamic response after a fluid challenge, antibiotics, source control and hemodynamic optimization or EGDT. This review will examine one decade of evidence for the components of the RB examining its impact on systemic inflammation, the progression of organ failure, health care resource consumption and mortality in severe sepsis and septic shock.
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Intervención Médica Temprana , Sepsis/terapia , Choque Séptico/terapia , Algoritmos , Humanos , Ácido Láctico , Resucitación , Factores de TiempoRESUMEN
BACKGROUND: Limited research exists on rehabilitative techniques focused on reducing disabilities after cerebral hemispherectomy despite persistent hemiparesis. OBJECTIVES: The efficacy of Intensive Mobility Training (IMT) for improving gait, balance and mobility was evaluated in patients after cerebral hemispherectomy and compared with clinical variables for signs of developmental neuroplasticity. METHODS: Participants (N.=19; 13.8±5.7 years) postcerebral hemispherectomy received IMT, three hours/day for 10 days. Outcomes measures were assessed pre- and post-intervention using the GAITRite electronic walkway® (velocity, toe in/out, step length of affected an unaffected leg), Dynamic Gait Index, Fugl-Meyer Scale, Berg Balance Scale, Timed Up and Go and Six-Minute Walk Test. Six of the nine measures that showed moderate effect sizes were incorporated into a Combined Functional Index (CFI) to assess global impact of therapy. RESULTS: After IMT, improvements were identified for toe in/out, step length of unaffected leg, Dynamic Gait Index, Berg Balance Scale and Six-Minute Walk (P<0.05; Effect Size 0.36-0.50). Using CFI for these six measures, patients improved from 77.3% to 82.7% (+5.3±3.7%) of normal following IMT. Improvements in CFI were greater in patients five years or younger at time of surgery (+7.7±3.6%) compared with older patients (+3.2±2.5%), and this accounted for 22% of variability in the change in score. CONCLUSION: The younger the participant at time of surgery correlated with the greatest improvements following IMT. These findings support the concept that the remaining hemisphere retains greater neuroplasticity if the contralateral surgery occurs earlier in cerebral development.
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Terapia por Ejercicio/métodos , Marcha/fisiología , Hemisferectomía/rehabilitación , Equilibrio Postural/fisiología , Caminata/fisiología , Adolescente , Adulto , Factores de Edad , Niño , Preescolar , Femenino , Humanos , Lactante , Los Angeles , Masculino , Plasticidad Neuronal/fisiología , Recuperación de la Función , Adulto JovenRESUMEN
Numerous reports have questioned the ability of United States emergency departments to handle the increasing demand for emergency services. Emergency department (ED) overcrowding is widespread in US cities and has reportedly reached crisis proportions. The purpose of this review is to describe how ED overcrowding threatens patient safety and public health, and to explore the complex causes and potential solutions for the overcrowding crisis. A review of the literature from 1990 to 2002 identified by a search of the Medline database was performed. Additional sources were selected from the references of the articles identified. There were four key findings. (1) The ED is a vital component of America's health care "safety net". (2) Overcrowding in ED treatment areas threatens public health by compromising patient safety and jeopardising the reliability of the entire US emergency care system. (3) Although the causes of ED overcrowding are complex, the main cause is inadequate inpatient capacity for a patient population with an increasing severity of illness. (4) Potential solutions for ED overcrowding will require multidisciplinary system-wide support.
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Ocupación de Camas/estadística & datos numéricos , Servicio de Urgencia en Hospital/estadística & datos numéricos , Aglomeración , Servicio de Urgencia en Hospital/organización & administración , Servicio de Urgencia en Hospital/normas , Accesibilidad a los Servicios de Salud , Capacidad de Camas en Hospitales , Planificación Hospitalaria , Humanos , Relaciones Interprofesionales , Errores Médicos , Admisión del Paciente , Factores de Riesgo , Seguridad , Estados UnidosRESUMEN
In the initial treatment of a critically ill patient, blood pressure, heart rate, urine output, and central venous pressure guide resuscitative efforts. Despite normalization of these variables, global tissue hypoxia may still persist and has been implicated in the development of multiorgan failure and increased mortality. Definitive management includes intensive care unit admission, pulmonary artery catheterization using mixed venous oxygen saturation (SvO2), and hemodynamic optimization. In the absence of or before definitive management, hemodynamic optimization can be performed using central venous oxygen saturation (ScvO2) as a surrogate. The physiology, technology, clinical uses, and rationale for ScvO2 monitoring are reviewed, including issues regarding physiologic equivalence to SvO2. The clinical use of ScvO2 monitoring, evidence-based outcome implications, and limitations of ScvO2 monitoring will also be examined.
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Monitoreo de Gas Sanguíneo Transcutáneo/métodos , Cuidados Críticos/métodos , Oxígeno/sangre , Paro Cardíaco/sangre , Humanos , Choque/sangre , Choque/etiologíaRESUMEN
STUDY OBJECTIVES: To examine the incidence and response to treatment of adrenal insufficiency (AI) in high-risk postoperative patients. DESIGN: Prospective observational case series. SETTING: Large urban tertiary-care surgical ICU (SICU). PARTICIPANTS: Adults > 55 years of age who required vasopressor therapy after adequate volume resuscitation in the immediate postoperative period. INTERVENTIONS: Each patient underwent a cosyntropin (ACTH) stimulation test; at the discretion of the clinical team, some patients were empirically given hydrocortisone (100 mg IV q8h for three doses) before serum cortisol values became available. MEASUREMENTS: Adrenal dysfunction (AD), defined as serum cortisol < 20 microg/dL at all time points, with Delta cortisol (60 min post-ACTH minus baseline) of < or = 9 microg/dL; functional hypoadrenalism (FH), defined as serum cortisol < 30 microg/dL at all time points or Delta cortisol (60 min post-ACTH minus baseline) < or = 9 microg/dL; and AI, as the presence of either AD or FH. RESULTS: One hundred four patients were enrolled with a mean age (SD) of 65.2 +/- 16.9 years. AI (AD plus FH) was found in 34 of 104 patients (32.7%): AD was found in 9 patients (8.7%), FH in 25 patients (24%), and normal adrenal function in 70 patients (67.3%). The absolute eosinophil count was significantly higher in the combined AD and FH groups compared with the group with normal adrenal function (p < 0.05). Forty-six of 104 patients (44.2%) received hydrocortisone; 29 (63%) could be weaned from treatment with vasopressors within 24 h. This beneficial effect of hydrocortisone reached statistical significance in the FH group when compared with untreated patients (p < 0.031); a similar trend was seen in the AD group (p = 0.083). Mortality was also lower in the hydrocortisone-treated AI patients (5 of 23 [21%] vs 5 of 11 [45%] in those not receiving hydrocortisone; p < 0.01). CONCLUSION: There is a high incidence of AI among SICU patients > 55 years of age with postoperative hypotension requiring vasopressors. There is also a significant association between hydrocortisone replacement therapy, resolution of vasopressor requirements, and improved survival.
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Insuficiencia Suprarrenal/epidemiología , Enfermedad Crítica , Unidades de Cuidados Intensivos , Complicaciones Posoperatorias/epidemiología , Insuficiencia Suprarrenal/terapia , Anciano , Cosintropina , Femenino , Humanos , Hidrocortisona/sangre , Hidrocortisona/uso terapéutico , Hipotensión/tratamiento farmacológico , Incidencia , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/tratamiento farmacológico , Estudios Prospectivos , Factores de Riesgo , Vasoconstrictores/uso terapéuticoRESUMEN
BACKGROUND: Goal-directed therapy has been used for severe sepsis and septic shock in the intensive care unit. This approach involves adjustments of cardiac preload, afterload, and contractility to balance oxygen delivery with oxygen demand. The purpose of this study was to evaluate the efficacy of early goal-directed therapy before admission to the intensive care unit. METHODS: We randomly assigned patients who arrived at an urban emergency department with severe sepsis or septic shock to receive either six hours of early goal-directed therapy or standard therapy (as a control) before admission to the intensive care unit. Clinicians who subsequently assumed the care of the patients were blinded to the treatment assignment. In-hospital mortality (the primary efficacy outcome), end points with respect to resuscitation, and Acute Physiology and Chronic Health Evaluation (APACHE II) scores were obtained serially for 72 hours and compared between the study groups. RESULTS: Of the 263 enrolled patients, 130 were randomly assigned to early goal-directed therapy and 133 to standard therapy; there were no significant differences between the groups with respect to base-line characteristics. In-hospital mortality was 30.5 percent in the group assigned to early goal-directed therapy, as compared with 46.5 percent in the group assigned to standard therapy (P = 0.009). During the interval from 7 to 72 hours, the patients assigned to early goal-directed therapy had a significantly higher mean (+/-SD) central venous oxygen saturation (70.4+/-10.7 percent vs. 65.3+/-11.4 percent), a lower lactate concentration (3.0+/-4.4 vs. 3.9+/-4.4 mmol per liter), a lower base deficit (2.0+/-6.6 vs. 5.1+/-6.7 mmol per liter), and a higher pH (7.40+/-0.12 vs. 7.36+/-0.12) than the patients assigned to standard therapy (P < or = 0.02 for all comparisons). During the same period, mean APACHE II scores were significantly lower, indicating less severe organ dysfunction, in the patients assigned to early goal-directed therapy than in those assigned to standard therapy (13.0+/-6.3 vs. 15.9+/-6.4, P < 0.001). CONCLUSIONS: Early goal-directed therapy provides significant benefits with respect to outcome in patients with severe sepsis and septic shock.
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Mortalidad Hospitalaria , Monitoreo Fisiológico , Sepsis/terapia , APACHE , Anciano , Algoritmos , Presión Sanguínea , Fármacos Cardiovasculares/uso terapéutico , Servicio de Urgencia en Hospital , Transfusión de Eritrocitos , Femenino , Fluidoterapia , Recursos en Salud/estadística & datos numéricos , Hemodinámica , Hospitales Urbanos , Humanos , Masculino , Persona de Mediana Edad , Oxígeno/sangre , Estudios Prospectivos , Sepsis/fisiopatología , Choque Séptico/fisiopatología , Choque Séptico/terapia , Método Simple Ciego , Síndrome de Respuesta Inflamatoria Sistémica/fisiopatología , Síndrome de Respuesta Inflamatoria Sistémica/terapia , Resultado del TratamientoRESUMEN
OBJECTIVES: The changing landscape of health care in this country has seen an increase in the delivery of care to critically ill patients in the emergency department (ED). However, methodologies to assess care and outcomes similar to those used in the intensive care unit (ICU) are currently lacking in this setting. This study examined the impact of ED intervention on morbidity and mortality using the Acute Physiology and Chronic Health Evaluation (APACHE II), the Simplified Acute Physiology Score (SAPS II), and the Multiple Organ Dysfunction Score (MODS). METHODS: This was a prospective, observational cohort study over a three-month period. Critically ill adult patients presenting to a large urban ED and requiring ICU admission were enrolled. APACHE II, SAPS II, and MODS scores and predicted mortality were obtained at ED admission, ED discharge, and 24, 48, and 72 hours in the ICU. In-hospital mortality was recorded. RESULTS: Eighty-one patients aged 64 +/- 18 years were enrolled during the study period, with a 30.9% in-hospital mortality. The ED length of stay was 5.9 +/- 2.7 hours and the hospital length of stay was 12.2 +/- 16.6 days. Nine (11.1%) patients initially accepted for ICU admission were later admitted to the general ward after ED intervention. Septic shock was the predominant admitting diagnosis. At ED admission, there was a significantly higher APACHE II score in nonsurvivors (23.0 +/- 6.0) vs survivors (19.8 +/- 6.5, p = 0.04), while there was no significant difference in SAPS II or MODS scores. The APACHE II, SAPS II, and MODS scores were significantly lower in survivors than nonsurvivors throughout the hospital stay (p
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Enfermedad Crítica/terapia , Servicio de Urgencia en Hospital , Indicadores de Salud , Evaluación de Resultado en la Atención de Salud , APACHE , Anciano , Análisis de Varianza , Área Bajo la Curva , Distribución de Chi-Cuadrado , Cuidados Críticos , Mortalidad Hospitalaria , Humanos , Tiempo de Internación/estadística & datos numéricos , Persona de Mediana Edad , Insuficiencia Multiorgánica/etiología , Estudios Prospectivos , Sensibilidad y Especificidad , Choque Séptico/complicaciones , Choque Séptico/terapia , Análisis de Supervivencia , Población UrbanaRESUMEN
OBJECTIVE: To examine the presence of interleukin-1 (IL-1), interleukin-6 (IL-6), and creatine phosphokinase-MM (CPK-MM) in patients with acute scrotal pain and assess their clinical utility in the diagnosis of testicular torsion (TT) and epididymitis. METHODS: Twenty-five patients with acute scrotal pain were prospectively enrolled over a two-year period. History, physical examination, complete blood count, urinalysis, and scrotal ultrasound were performed. Testicular torsion was confirmed by surgical exploration. Epididymitis was diagnosed using physical examination, scrotal ultrasound, and positive urinalysis. Venous blood was assayed for IL-1, IL-6, and CPK-MM in triplicate during the routine drawing of blood in the emergency department. The data are reported as medians +/- interquartile ranges (IQRs). RESULTS: Twenty-five patients with acute scrotal pain were evaluated; 11 with TT, three with torsion of the appendix testis (TAT), ten with epididymitis, and one with varicocele. One patient had both TT and epididymitis. Interleukin-1 was not detectable in either group. The CPK-MM values between TT and epididymitis were virtually identical at 99.8 and 100 IU/L, respectively. The median value for IL-6 was 1. 03 (IQR = 0.19 to 2.86) vs 20.86 (IQR = 2.14 to 65.50) pg/mL in the torsion and epididymitis groups, respectively. The 97.5% CI for the difference of medians of 19.9 was 0.4 to 65.1, p = 0.02. Using receiver operating characteristic (ROC) curve analysis for IL-6, the area under the curve was 0.82 for torsion and 0.67 for epididymitis. Using a cutoff value of IL-6 >/= 1.41 pg/mL, the positive predictive value of IL-6 in diagnosing epididymitis was 78.6%, with a negative predictive value of 100% for TT. There were no cases of missed TT on follow-up. CONCLUSIONS: This preliminary investigation of serologic markers demonstrates that IL-6 is significantly elevated in epididymitis as compared with TT. Creatine phosphokinase-MM and IL-1 were not found to be of diagnostic utility. The small sample size of this study precludes a definitive conclusion as to the utility of these markers in the emergency department. However, IL-6 may be clinically useful as an additional element in differentiating the causes of acute scrotal pain, and further study is warranted.