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1.
Anaesthesia ; 76(2): 238-250, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33141959

RESUMEN

Intravenous lidocaine is used widely for its effect on postoperative pain and recovery but it can be, and has been, fatal when used inappropriately and incorrectly. The risk-benefit ratio of i.v. lidocaine varies with type of surgery and with patient factors such as comorbidity (including pre-existing chronic pain). This consensus statement aims to address three questions. First, does i.v. lidocaine effectively reduce postoperative pain and facilitate recovery? Second, is i.v. lidocaine safe? Third, does the fact that i.v. lidocaine is not licensed for this indication affect its use? We suggest that i.v. lidocaine should be regarded as a 'high-risk' medicine. Individual anaesthetists may feel that, in selected patients, i.v. lidocaine may be beneficial as part of a multimodal peri-operative pain management strategy. This approach should be approved by hospital medication governance systems, and the individual clinical decision should be made with properly informed consent from the patient concerned. If i.v. lidocaine is used, we recommend an initial dose of no more than 1.5 mg.kg-1 , calculated using the patient's ideal body weight and given as an infusion over 10 min. Thereafter, an infusion of no more than 1.5 mg.kg-1 .h-1 for no longer than 24 h is recommended, subject to review and re-assessment. Intravenous lidocaine should not be used at the same time as, or within the period of action of, other local anaesthetic interventions. This includes not starting i.v. lidocaine within 4 h after any nerve block, and not performing any nerve block until 4 h after discontinuing an i.v. lidocaine infusion.


Asunto(s)
Anestésicos Locales/administración & dosificación , Anestésicos Locales/uso terapéutico , Lidocaína/administración & dosificación , Lidocaína/uso terapéutico , Dolor Postoperatorio/prevención & control , Administración Intravenosa , Anestésicos Locales/efectos adversos , Comorbilidad , Consenso , Humanos , Infusiones Intravenosas , Lidocaína/efectos adversos , Bloqueo Nervioso , Seguridad del Paciente , Recuperación de la Función , Medición de Riesgo , Resultado del Tratamiento
2.
Xenobiotica ; 51(1): 72-81, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32660295

RESUMEN

Fenarimol (FNL), an organic chlorinated fungicide, is widely used in agriculture for protection from fungal spores and fungi. Despite being an endocrine disruptor, no toxicokinetic data is reported for this fungicide. In the present work, we determined the plasma protein binding, metabolic pathways and toxicokinetics of FNL in rats. In vitro binding of FNL to rat and human plasma proteins was ∼90%, suggesting that FNL is a highly protein bound fungicide. The predicted in vivo hepatic clearance of FNL in rats and humans was estimated to be 36.71 and 14.39 mL/min/kg, respectively, indicating it to be an intermediate clearance compound. Reaction phenotyping assay showed that CYP3A4 mainly contributed to the overall metabolism of FNL. The oral toxicokinetic study of FNL in rats at no observed adverse effect level dose (1 mg/kg) showed maximum plasma concentration (C max) of 33.97 ± 4.45 ng/mL at 1 h (T max). The AUC0-∞ obtained was 180.18 ± 17.76 h*ng/mL, whereas, the t 1/2 was ∼4.74 h. Following intravenous administration, FNL displayed a clearance of 42.48 mL/min/kg which was close to the predicted in vivo hepatic clearance. The absolute oral bioavailability of FNL at 1 mg/kg dose in rats was 45.25%. FNL at 10 mg/kg oral dose exhibited non-linear toxicokinetics with greater than dose-proportional increase in the systemic exposure (AUC0-∞ 8270.53 ± 1798.59 h*ng/mL).


Asunto(s)
Fungicidas Industriales/metabolismo , Pirimidinas/metabolismo , Administración Intravenosa , Administración Oral , Animales , Área Bajo la Curva , Disponibilidad Biológica , Disruptores Endocrinos , Fungicidas Industriales/toxicidad , Infusiones Intravenosas , Unión Proteica , Pirimidinas/toxicidad , Ratas , Toxicocinética
3.
Xenobiotica ; 51(2): 202-209, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32930648

RESUMEN

Lumefantrine (LFN) is a chiral antimalarial drug. Enantioselective in vitro attributes and absolute oral pharmacokinetics for (-)-LFN and (+)-LFN have been characterized in mice. No stereoselectivity was seen with either of the enantiomers when compared with rac-LFN in the executed in vitro studies (solubility, metabolic stability, protein binding, permeability and blood partitioning). Post intravenous or oral administration of rac-LFN, the AUC0-∞ and MRT of (+)-LFN was higher over (-)-LFN, which is reflected in higher clearance value for (-)-LFN. Following (-)-LFN intravenous administration to mice, the key PK parameters were comparable to (-)-LFN from rac-LFN; however, post intravenous administration of (+)-LFN alone to mice, the AUC0-∞ was 1.3-fold higher than (+)-LFN from rac-LFN. Similarly, post oral administration of (-)-LFN to mice, both AUC0-∞ and Cmax were 1.3-fold higher than (-)-LFN from rac-LFN. On other hand, (+)-LFN showed 1.4-fold higher AUC0-∞ and 1.7-fold higher Cmax post oral administration over (+)-LFN from rac-LFN.


Asunto(s)
Antimaláricos/farmacocinética , Lumefantrina/farmacocinética , Administración Oral , Animales , Disponibilidad Biológica , Etanolaminas , Infusiones Intravenosas , Masculino , Ratones , Solubilidad , Estereoisomerismo
4.
Ann Vasc Surg ; 70: 297-301, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32861850

RESUMEN

SARS-CoV-2 (COVID-19) patients with associated thromboembolic events have demonstrated poor outcomes despite the use of anticoagulation therapy and surgical intervention. We present a COVID-19 patient with acute limb ischemia, secondary to extensive thrombosis of an aortic aneurysm, iliac arteries, and infrainguinal arteries. Initial treatment with systemic thrombolysis, which restored patency of the aortoiliac occlusion, was followed by open thrombectomies of the infrainguinal occlusions.


Asunto(s)
Aneurisma de la Aorta Abdominal/complicaciones , Arteriopatías Oclusivas/tratamiento farmacológico , Fibrinolíticos/administración & dosificación , Arteria Ilíaca , Terapia Trombolítica , Trombosis/tratamiento farmacológico , Activador de Tejido Plasminógeno/administración & dosificación , Anciano , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Arteriopatías Oclusivas/diagnóstico por imagen , Arteriopatías Oclusivas/etiología , Arteriopatías Oclusivas/fisiopatología , Humanos , Arteria Ilíaca/diagnóstico por imagen , Arteria Ilíaca/fisiopatología , Infusiones Intravenosas , Masculino , Trombectomía , Trombosis/diagnóstico por imagen , Trombosis/etiología , Trombosis/fisiopatología , Resultado del Tratamiento , Grado de Desobstrucción Vascular
5.
J Surg Res ; 257: 32-41, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32818782

RESUMEN

BACKGROUND: Older patients often have iron deficiency anemia before surgery, which can be effectively treated with intravenous iron supplementation (IVIS). Anemia and blood transfusions are associated with an increased risk of delirium. The aim of this research was to assess the effectiveness and safety of using IVIS in a prehabilitation program. MATERIAL AND METHODS: Patients ≥70 y who underwent abdominal surgery between November 2015 and June 2018 were included in this single-center prospective cohort study. All patients were prehabilitated; however, only anemic patients received a single dose of 1000 mg intravenous iron (ferric carboxymaltose) to increase preoperative hemoglobin levels (IVIS group). Nonanemic patients received standard care (SC). The hemoglobin levels (primary outcome) were assessed at the outpatient clinic visit, at admission, and at discharge. Secondary outcomes were postoperative delirium, postoperative anemia, blood transfusion, complications other than delirium, and length of hospital stay. All outcomes were compared between the IVIS group and SC group. RESULTS: Of all patients (n = 248), 97 anemic patients received IVIS (39%). Of the anemic patients, 50 patients (52%) had iron deficiency. Initial differences in hemoglobin concentrations between the IVIS group and SC group at T1 and T2 (7.2 versus 8.8; P < 0.001 and 7.4 versus 8.6; P = 0.023, respectively) were no longer present at discharge (6.6 versus 7.2; P = 0.35). No statistically significant differences were observed for all secondary outcomes between the IVIS group and the SC group. No infusion-related adverse events occurred. CONCLUSIONS: Adding IVIS to prehabilitation programs is safe and diminishes differences in these concentrations between preoperatively anemic and nonanemic patients. IVIS may be worthwhile as an additional component of prehabilitation programs. Results merit further investigation.


Asunto(s)
Hierro/administración & dosificación , Cuidados Preoperatorios/métodos , Abdomen/cirugía , Anciano , Anciano de 80 o más Años , Anemia/epidemiología , Anemia Ferropénica/tratamiento farmacológico , Anemia Ferropénica/epidemiología , Transfusión Sanguínea/estadística & datos numéricos , Estudios de Cohortes , Delirio/epidemiología , Procedimientos Quirúrgicos Electivos , Femenino , Hemoglobinas/análisis , Humanos , Infusiones Intravenosas , Masculino , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Estudios Prospectivos
6.
Einstein (Sao Paulo) ; 18: eRC5606, 2020.
Artículo en Inglés, Portugués | MEDLINE | ID: mdl-33295434

RESUMEN

Case report of a patient with an immunodeficiency who demands regular replacement of intravenous immunoglobulin. She presented an episode of transfusion-related acute lung injury shortly after using an immunoglobulin product different than the one she usually received. The patient evolved with respiratory changes (hypoxia, dyspnea, change in pulmonary auscultation) minutes after the end of the infusion, and received non-invasive respiratory support. She was discharged after 36 hours with good outcome. The patient achieved full recovery, showing no further reactions in subsequent immunoglobulin infusions (no longer receiving the product that was used when she had the episode of transfusion-related acute lung injury). Although rare, this reaction is potentially serious and has no specific treatment other than supportive therapy. The literature is scarce regarding the risk of recurrence. The decision on whether to proceed with immunoglobulin therapy after this adverse effect should be analyzed individually, assessing the possible risks and benefits for the patient.


Asunto(s)
Síndromes de Inmunodeficiencia , Enfermedades Pulmonares , Lesión Pulmonar Aguda Postransfusional , Adulto , Anciano , Femenino , Humanos , Inmunoglobulinas Intravenosas/efectos adversos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad
8.
Medicine (Baltimore) ; 99(49): e23401, 2020 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-33285727

RESUMEN

BACKGROUND: Corona virus disease 2019 (COVID-19) is an epidemic respiratory infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 infection. Now it is popular all over the world on a large scale. COVID-19 has the characteristics of rapid transmission, atypical clinical symptoms, easy missed diagnosis and misdiagnosis, and so on. which has seriously affected social and economic development and people's health. Severe acute respiratory syndrome corona virus type 2 infection may lead to systemic cytokine storm, which leads to a sharp deterioration of the condition of ordinary patients. At present, no specific drug has been found in the clinical treatment of covid-19, while Xuebijing injection has been widely used in severe patients in China as a traditional Chinese medicine. The aim of this study is to assess the effificacy and safety of Xuebijing injection for COVID-19. METHODS: Before the research, we conducted a comprehensive search on relevant websites. Two professional researchers will gradually screen, read the title, abstract and full text if necessary, and independently select qualified documents according to the inclusion and exclusion criteria. We will conduct a meta-analysis of the results related to COVID-19 to assess the risks of bias and data extraction. The heterogeneity of data will be studied by Cochrane X and I tests. The evaluation of publication bias will be carried out by funnel chart analysis and Eger test. RESULTS: This review will be disseminated in print by peer-review. CONCLUSION: Our research is to scientifically analyze the clinical evidence of Xuebijing injection in treating severe COVID-19 patients.


Asunto(s)
/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , /fisiopatología , Ensayos Clínicos como Asunto , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/efectos adversos , Humanos , Infusiones Intravenosas , Medicina China Tradicional , Pandemias , Proyectos de Investigación , Índice de Severidad de la Enfermedad
9.
Medicine (Baltimore) ; 99(50): e23515, 2020 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-33327295

RESUMEN

BACKGROUND: Total knee arthroplasty (TKA) is gradually emerging as the treatment of choice for end-stage osteoarthritis. In the past, intravenous (IV) versus oral acetaminophen (APAP) treatment is still a controversial subject in TKA. Therefore, we write this systematic review and meta-analysis to evaluate the efficacy of IV versus oral APAP on pain and recovery after TKA. METHODS: Embase, Pubmed, and Cochrane Library were comprehensively searched. Randomized controlled trials, cohort studies were included in our meta-analysis. Five studies that compared IV APAP groups with oral APAP groups were included in our meta-analysis. The research was reported according to the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines to ensure the reliability and verity of results. RESULTS: Pooled results indicated that no significant difference between the IV APAP groups and oral APAP groups in term of VAS score at 24 hours (P = .67), 48 hours (P = 0.08), and total morphine consumption at 24 hours (P = .07), but there was a significant difference in terms of length of hospital stay (LOS) (P = .0004). CONCLUSION: IV APAP was not found to be superior to oral APAP in patients undergoing TKA in terms of VAS scores at 24 hours, 48 hours, and total morphine consumption at 24 hours. However, it can significantly reduce the LOS. We still need a large of high-quality research to verify the relationship between the oral and the IV APAP to give the conclusion.


Asunto(s)
Acetaminofén/administración & dosificación , Analgésicos no Narcóticos/administración & dosificación , Artroplastia de Reemplazo de Rodilla , Dolor Postoperatorio/tratamiento farmacológico , Administración Oral , Humanos , Infusiones Intravenosas , Recuperación de la Función
10.
Yakugaku Zasshi ; 140(11): 1373-1380, 2020.
Artículo en Japonés | MEDLINE | ID: mdl-33132273

RESUMEN

The treatment of acute ischemic stroke usually involves argatroban administration by continuous infusion for 2 d and by intravenous infusion twice a day for 5 d after that. However, the appropriate dose of argatroban to be administered is not clear. Therefore, no studies have been reported a comparison of intravenous and continuous argatroban infusion after day 3 for acute ischemic stroke patients. We aimed to identify the connection between differences in argatroban administration and worsening of symptoms after day 3 in ischemic stroke patients. We retrospectively evaluated the data of 107 ischemic stroke patients who received treatment with argatroban. The study endpoint was defined as the worsening of symptoms from days 3 to 7. Logistic regression analysis was used to determine the risk factors that were significantly associated with worsening of symptoms. Patients were administered argatroban, with rates of 72.0%, and 28.0% for continuous, and intravenous infusion, respectively. A total of 10 (9.3%) patients experienced worsening of symptoms. In the single logistic regression analysis, carotid stenosis [non-adjusted odds ratio (OR) 5.775, 95% confidence interval (CI) 1.486-22.442, p=0.011] was only significantly associated with worsening of symptoms. Worsening of symptoms was not related to either intravenous or continuous infusion group (16.7% vs. 6.5%, p=0.104). Bleeding was also not associated with either group (6.7% vs. 3.9%, p=0.618). We suggest that the differences in the mode of argatroban administration were not related to the worsening of symptoms in ischemic stroke patients. We also found that safety was equivalent regardless of the administration route.


Asunto(s)
Administración Intravenosa/métodos , Ácidos Pipecólicos/administración & dosificación , Accidente Cerebrovascular/tratamiento farmacológico , Brote de los Síntomas , Anciano , Anciano de 80 o más Años , Vías de Administración de Medicamentos , Femenino , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Evaluación del Resultado de la Atención al Paciente , Ácidos Pipecólicos/efectos adversos , Estudios Retrospectivos , Seguridad
11.
JAMA Netw Open ; 3(11): e2024596, 2020 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-33196806

RESUMEN

Importance: Saline (0.9% sodium chloride), the fluid most commonly used to treat diabetic ketoacidosis (DKA), can cause hyperchloremic metabolic acidosis. Balanced crystalloids, an alternative class of fluids for volume expansion, do not cause acidosis and, therefore, may lead to faster resolution of DKA than saline. Objective: To compare the clinical effects of balanced crystalloids with the clinical effects of saline for the acute treatment of adults with DKA. Design, Setting, and Participants: This study was a subgroup analysis of adults with DKA in 2 previously reported companion trials-Saline Against Lactated Ringer's or Plasma-Lyte in the Emergency Department (SALT-ED) and the Isotonic Solutions and Major Adverse Renal Events Trial (SMART). These trials, conducted between January 2016 and March 2017 in an academic medical center in the US, were pragmatic, multiple-crossover, cluster, randomized clinical trials comparing balanced crystalloids vs saline in emergency department (ED) and intensive care unit (ICU) patients. This study included adults who presented to the ED with DKA, defined as a clinical diagnosis of DKA, plasma glucose greater than 250 mg/dL, plasma bicarbonate less than or equal to 18 mmol/L, and anion gap greater than 10 mmol/L. Data analysis was performed from January to April 2020. Interventions: Balanced crystalloids (clinician's choice of Ringer lactate solution or Plasma-Lyte A solution) vs saline for fluid administration in the ED and ICU according to the same cluster-randomized multiple-crossover schedule. Main Outcomes and Measures: The primary outcome was time between ED presentation and DKA resolution, as defined by American Diabetes Association criteria. The secondary outcome was time between initiation and discontinuation of continuous insulin infusion. Results: Among 172 adults included in this secondary analysis of cluster trials, 94 were assigned to balanced crystalloids and 78 to saline. The median (interquartile range [IQR]) age was 29 (24-45) years, and 90 (52.3%) were women. The median (IQR) volume of isotonic fluid administered in the ED and ICU was 4478 (3000-6372) mL. Cumulative incidence analysis revealed shorter time to DKA resolution in the balanced crystalloids group (median time to resolution: 13.0 hours; IQR: 9.5-18.8 hours) than the saline group (median: 16.9 hours; IQR: 11.9-34.5 hours) (adjusted hazard ratio [aHR] = 1.68; 95% CI, 1.18-2.38; P = .004). Cumulative incidence analysis also revealed shorter time to insulin infusion discontinuation in the balanced crystalloids group (median: 9.8 hours; IQR: 5.1-17.0 hours) than the saline group (median: 13.4 hours; IQR: 11.0-17.9 hours) (aHR = 1.45; 95% CI, 1.03-2.03; P = .03). Conclusions and Relevance: In this secondary analysis of 2 cluster randomized clinical trials, compared with saline, treatment with balanced crystalloids resulted in more rapid resolution of DKA, suggesting that balanced crystalloids may be preferred over saline for acute management of adults with DKA. Trial Registration: ClinicalTrials.gov Identifiers: NCT02614040; NCT02444988.


Asunto(s)
Soluciones Cristaloides/uso terapéutico , Cetoacidosis Diabética/tratamiento farmacológico , Fluidoterapia/estadística & datos numéricos , Solución Salina Hipertónica/uso terapéutico , Acidosis/inducido químicamente , Acidosis/prevención & control , Adulto , Análisis por Conglomerados , Estudios Cruzados , Soluciones Cristaloides/efectos adversos , Cetoacidosis Diabética/sangre , Cetoacidosis Diabética/diagnóstico , Electrólitos/sangre , Servicio de Urgencia en Hospital/estadística & datos numéricos , Femenino , Fluidoterapia/métodos , Humanos , Infusiones Intravenosas/métodos , Insulina/administración & dosificación , Insulina/uso terapéutico , Unidades de Cuidados Intensivos/estadística & datos numéricos , Soluciones Isotónicas/administración & dosificación , Soluciones Isotónicas/efectos adversos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Solución Salina Hipertónica/efectos adversos , Factores de Tiempo
12.
J Clin Psychiatry ; 81(6)2020 11 10.
Artículo en Inglés | MEDLINE | ID: mdl-33176071

RESUMEN

BACKGROUND: Studies have reported that ketamine potentially increases subjective happiness in healthy volunteers. However, whether ketamine-induced happiness can predict the treatment response of ketamine infusion among patients with treatment-resistant depression (TRD) remains unknown. METHODS: Between 2012 and 2015, 71 adult patients with TRD (based on DSM-IV-TR criteria) were enrolled and randomly assigned to receive a 40-minute ketamine (0.5 mg/kg or 0.2 mg/kg) or normal saline placebo infusion. Depressive symptoms were measured using the 17-item Hamilton Depression Rating Scale. Measurements were conducted prior to infusion, at 40 and 240 minutes postinfusion, and, sequentially, on days 2 to 7 and 14 postinfusion. The visual analog scale for happiness (VASH) was used to assess happiness during infusion. The positive symptoms subscale of the Brief Psychiatric Rating Scale (BPRS-P) was used to measure the potential psychotomimetic effects of ketamine. RESULTS: For both the 2-factor (ketamine vs placebo) and 3-factor (ketamine 0.5 mg/kg vs 0.2 mg/kg vs placebo) models, a generalized estimating equation model indicated that infusion response type (happiness vs nonhappiness) significantly (P = .008 vs P = .002) predicted the trajectory of depressive symptoms after infusion. Changes in VASH and BPRS-P measures were not associated with each other. CONCLUSIONS: Subjective happiness during ketamine infusion predicted the antidepressant effect of both 0.5 mg/kg and 0.2 mg/kg ketamine infusion over time. Happiness during ketamine infusion, which was not related to the psychotomimetic effect of ketamine, may be associated with the reduction of depressive symptoms during the follow-up. TRIAL REGISTRATION: UMIN Clinical Trials Registry registration number: UMIN000016985.


Asunto(s)
Trastorno Depresivo Resistente al Tratamiento/tratamiento farmacológico , Antagonistas de Aminoácidos Excitadores/farmacología , Felicidad , Ketamina/farmacología , Evaluación de Resultado en la Atención de Salud , Adulto , Trastorno Depresivo Resistente al Tratamiento/fisiopatología , Antagonistas de Aminoácidos Excitadores/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Infusiones Intravenosas , Ketamina/administración & dosificación , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Taiwán
13.
Lancet ; 396(10262): 1574-1584, 2020 11 14.
Artículo en Inglés | MEDLINE | ID: mdl-33176180

RESUMEN

BACKGROUND: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers. METHODS: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0-1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0-2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4-6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903. FINDINGS: Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10-2·03]; p=0·011), with low heterogeneity across studies (I2=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05-1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06-2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4-6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52-1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03-4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [<1%], adjusted OR 5·58 [1·22-25·50]; p=0·024). INTERPRETATION: In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death. FUNDING: None.


Asunto(s)
Fibrinolíticos/uso terapéutico , /tratamiento farmacológico , Tiempo de Tratamiento , Activador de Tejido Plasminógeno/uso terapéutico , Imagen de Difusión por Resonancia Magnética/métodos , Fibrinolíticos/efectos adversos , Humanos , Infusiones Intravenosas , Recuperación de la Función , Activador de Tejido Plasminógeno/efectos adversos , Tomografía Computarizada por Rayos X/métodos , Resultado del Tratamiento
14.
N Engl J Med ; 383(24): 2307-2319, 2020 12 10.
Artículo en Inglés | MEDLINE | ID: mdl-33196153

RESUMEN

BACKGROUND: Patients with refractory hypercholesterolemia, who have high low-density lipoprotein (LDL) cholesterol levels despite treatment with lipid-lowering therapies at maximum tolerated doses, have an increased risk of atherosclerosis. In such patients, the efficacy and safety of subcutaneous and intravenous evinacumab, a fully human monoclonal antibody against angiopoietin-like 3, are not known. METHODS: In this double-blind, placebo-controlled, phase 2 trial, we enrolled patients with or without heterozygous familial hypercholesterolemia who had refractory hypercholesterolemia, with a screening LDL cholesterol level of 70 mg per deciliter or higher with atherosclerosis or of 100 mg per deciliter or higher without atherosclerosis. Patients were randomly assigned to receive subcutaneous or intravenous evinacumab or placebo. The primary end point was the percent change from baseline in the LDL cholesterol level at week 16 with evinacumab as compared with placebo. RESULTS: In total, 272 patients were randomly assigned to the following groups: subcutaneous evinacumab at a dose of 450 mg weekly (40 patients), 300 mg weekly (43 patients), or 300 mg every 2 weeks (39 patients) or placebo (41 patients); or intravenous evinacumab at a dose of 15 mg per kilogram of body weight every 4 weeks (39 patients) or 5 mg per kilogram every 4 weeks (36 patients) or placebo (34 patients). At week 16, the differences in the least-squares mean change from baseline in the LDL cholesterol level between the groups assigned to receive subcutaneous evinacumab at a dose of 450 mg weekly, 300 mg weekly, and 300 mg every 2 weeks and the placebo group were -56.0, -52.9, and -38.5 percentage points, respectively (P<0.001 for all comparisons). The differences between the groups assigned to receive intravenous evinacumab at a dose of 15 mg per kilogram and 5 mg per kilogram and the placebo group were -50.5 percentage points (P<0.001) and -24.2 percentage points, respectively. The incidence of serious adverse events during the treatment period ranged from 3 to 16% across trial groups. CONCLUSIONS: In patients with refractory hypercholesterolemia, the use of evinacumab significantly reduced the LDL cholesterol level, by more than 50% at the maximum dose. (Funded by Regeneron Pharmaceuticals; ClinicalTrials.gov number, NCT03175367.).


Asunto(s)
Proteínas Similares a la Angiopoyetina/antagonistas & inhibidores , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Anticolesterolemiantes/uso terapéutico , Hiperlipoproteinemia Tipo II/tratamiento farmacológico , Adulto , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticolesterolemiantes/administración & dosificación , Anticolesterolemiantes/efectos adversos , LDL-Colesterol/sangre , Método Doble Ciego , Esquema de Medicación , Resistencia a Medicamentos , Femenino , Humanos , Infusiones Intravenosas , Inyecciones Subcutáneas , Masculino , Persona de Mediana Edad
15.
Int Heart J ; 61(6): 1157-1164, 2020 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-33191351

RESUMEN

The aim of this study was to prospectively assess the efficacy, safety, and predictive effect of intravenous nifekalant administration for persistent atrial fibrillation (PerAF) after pulmonary vein isolation (PVI) with second-generation cryoballoon ablation (CBA) on 1-year atrial tachyarrhythmia (ATa) -free survival by examining the pharmacological conversion rate.One hundred and two drug-refractory, consecutive PerAF patients undergoing PVI were enrolled in this prospective observational study. After PVI, nifekalant (50 mg) was given followed by 30 minutes of observation and no further intervention. PerAF was successfully converted to sinus rhythm (SR) in 60 patients (58.8%) after a median time of 7.75 (4.13-12) minutes (group N). In the remaining 42 patients (41.2%) (group C), PerAF was successfully converted to SR by external electrical cardioversion. Nonsustained ventricular tachycardia occurred in 1 patient in group N. The left atrial volume (LAV) in group C was larger than that in group N (128.2 ± 28.2 versus 111.8 ± 24.5 mL, P = 0.002). Phrenic nerve injury occurred in 4 of 102 patients (3.9%). No other complications occurred during the procedure or within the 1-year follow-up period. At the 1-year follow-up, after a 3-month blanking period (BP), ATa-free survival during 1-year follow-up in group C was significantly lower than that in group N (50.0% versus 71.7%, P = 0.026), and the overall ATa-free survival rate was 62.7%. Two patients in group C and 4 patients in group N underwent a second procedure with radiofrequency catheter ablation. Multivariate Cox regression analysis demonstrated that unsuccessful conversion to SR (P = 0.025), ATa relapse during the BP (P = 0.000), and larger LAV (P = 0.016) were independent predictors of ATa recurrence at the 1-year follow-up.In conclusion, at the 1-year follow-up, the ATa-free survival rate after PVI with CBA for PerAF patients was 62.7%, and successful conversion to SR with nifekalant could serve as a clinical predictor of reduced ATa recurrence.


Asunto(s)
Antiarrítmicos/uso terapéutico , Fibrilación Atrial/terapia , Criocirugia/métodos , Cuidados Intraoperatorios/métodos , Venas Pulmonares/cirugía , Pirimidinonas/uso terapéutico , Anciano , Cardioversión Eléctrica/métodos , Femenino , Atrios Cardíacos/diagnóstico por imagen , Atrios Cardíacos/patología , Humanos , Infusiones Intravenosas , Complicaciones Intraoperatorias/epidemiología , Masculino , Persona de Mediana Edad , Tamaño de los Órganos , Traumatismos de los Nervios Periféricos/epidemiología , Nervio Frénico/lesiones , Supervivencia sin Progresión , Estudios Prospectivos , Recurrencia , Taquicardia Ventricular/epidemiología , Resultado del Tratamiento
16.
Medicine (Baltimore) ; 99(48): e23113, 2020 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-33235071

RESUMEN

BACKGROUND: Pulmonary surfactant (PS) is commonly used for the treatment of neonatal respiratory distress syndrome (NRDS), several randomized controlled trials (RCTs) have evaluated the role of nebulized versus invasively delivered PS, yet the results remained inconsistent. Therefore, we aimed to conduct this meta-analysis to evaluate the effects and safety of nebulized versus invasively delivered PS in the treatment of NRDS. METHODS: We searched PubMed et al databases from inception date to May 15, 2020 for RCTs that compared nebulized vs invasively delivered PS. Two authors independently screened the studies and extracted data from the published articles. Summary odd ratios (OR) or mean differences (MDs) with 95% confidence intervals (CIs) were calculated for each outcome by means of fixed- or random-effects model. RESULTS: Two RCTs with a total of 95 preterm neonates were identified, with 48 neonates received PS nebulization and 47 neonates undergone invasive PS administration. There was no significant difference in the SpO2 level (MD = -0.44, 95% CI -6.01 to 5.12) and the A/APaO2 level (MD = 0.01, 95% CI -0.02 to 0.05) 1 hour after treatment among 2 groups. But the duration of mechanical ventilation in the nebulization groups was significantly less than that of invasive group (MD = -30.70, 95% CI -41.45 to 19.95). CONCLUSIONS: Given the limited evidences, the effects and safety of nebulized versus invasively delivered PS still need further verification.


Asunto(s)
Surfactantes Pulmonares/administración & dosificación , Síndrome de Dificultad Respiratoria del Recién Nacido/tratamiento farmacológico , Administración por Inhalación , Humanos , Recién Nacido , Infusiones Intravenosas , Nebulizadores y Vaporizadores , Resultado del Tratamiento
17.
Mayo Clin Proc ; 95(11): 2382-2394, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33153629

RESUMEN

OBJECTIVE: To assess the efficacy and safety of lenzilumab in patients with severe coronavirus disease 2019 (COVID-19) pneumonia. METHODS: Hospitalized patients with COVID-19 pneumonia and risk factors for poor outcomes were treated with lenzilumab 600 mg intravenously for three doses through an emergency single-use investigational new drug application. Patient characteristics, clinical and laboratory outcomes, and adverse events were recorded. We also identified a cohort of patients matched to the lenzilumab patients for age, sex, and disease severity. Study dates were March 13, 2020, to June 18, 2020. All patients were followed through hospital discharge or death. RESULTS: Twelve patients were treated with lenzilumab; 27 patients comprised the matched control cohort (untreated). Clinical improvement, defined as improvement of at least 2 points on the 8-point ordinal clinical endpoints scale, was observed in 11 of 12 (91.7%) patients treated with lenzilumab and 22 of 27 (81.5%) untreated patients. The time to clinical improvement was significantly shorter for the lenzilumab-treated group compared with the untreated cohort with a median of 5 days versus 11 days (P=.006). Similarly, the proportion of patients with acute respiratory distress syndrome (oxygen saturation/fraction of inspired oxygen<315 mm Hg) was significantly reduced over time when treated with lenzilumab compared with untreated (P<.001). Significant improvement in inflammatory markers (C-reactive protein and interleukin 6) and markers of disease severity (absolute lymphocyte count) were observed in patients who received lenzilumab, but not in untreated patients. Cytokine analysis showed a reduction in inflammatory myeloid cells 2 days after lenzilumab treatment. There were no treatment-emergent adverse events attributable to lenzilumab. CONCLUSION: In high-risk COVID-19 patients with severe pneumonia, granulocyte-macrophage colony-stimulating factor neutralization with lenzilumab was safe and associated with faster improvement in clinical outcomes, including oxygenation, and greater reductions in inflammatory markers compared with a matched control cohort of patients hospitalized with severe COVID-19 pneumonia. A randomized, placebo-controlled clinical trial to validate these findings is ongoing (NCT04351152).


Asunto(s)
Anticuerpos Monoclonales Humanizados/administración & dosificación , Factor Estimulante de Colonias de Granulocitos y Macrófagos/antagonistas & inhibidores , Anciano , /metabolismo , Relación Dosis-Respuesta a Droga , Femenino , Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Pandemias , Resultado del Tratamiento
18.
PLoS One ; 15(11): e0242169, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33180816

RESUMEN

Severe chronic postsurgical pain has a prevalence of 4-10% in the surgical population. The underlying nociceptive mechanisms have not been well characterized. Following the late resolution phase of an inflammatory injury, high-dose µ-opioid-receptor inverse agonists reinstate hypersensitivity to nociceptive stimuli. This unmasking of latent pain sensitization has been a consistent finding in rodents while only observed in a limited number of human volunteers. Latent sensitization could be a potential triggering venue in chronic postsurgical pain. The objective of the present trial was in detail to examine the association between injury-induced secondary hyperalgesia and naloxone-induced unmasking of latent sensitization. Healthy volunteers (n = 80) received a cutaneous heat injury (47°C, 420 s, 12.5 cm2). Baseline secondary hyperalgesia areas were assessed 1 h post-injury. Utilizing an enriched enrollment design, subjects with a magnitude of secondary hyperalgesia areas in the upper quartile ('high-sensitizers' [n = 20]) and the lower quartile ('low-sensitizers' [n = 20]) were selected for further study. In four consecutive experimental sessions (Sessions 1 to 4), the subjects at two sessions (Sessions 1 and 3) received a cutaneous heat injury followed 168 h later (Sessions 2 and 4) by a three-step target-controlled intravenous infusion of naloxone (3.25 mg/kg), or normal saline. Assessments of secondary hyperalgesia areas were made immediately before and stepwise during the infusions. Simple univariate statistics revealed no significant differences in secondary hyperalgesia areas between naloxone and placebo treatments (P = 0.215), or between 'high-sensitizers' and 'low-sensitizers' (P = 0.757). In a mixed-effects model, secondary hyperalgesia areas were significantly larger following naloxone as compared to placebo for 'high-sensitizers' (P < 0.001), but not 'low-sensitizers' (P = 0.651). Although we could not unequivocally demonstrate naloxone-induced reinstatement of heat injury-induced hyperalgesia, further studies in clinical postsurgical pain models are warranted.


Asunto(s)
Hiperalgesia/fisiopatología , Naloxona/farmacología , Antagonistas de Narcóticos/farmacología , Nocicepción/efectos de los fármacos , Dolor/fisiopatología , Calor , Humanos , Infusiones Intravenosas , Masculino , Naloxona/administración & dosificación , Antagonistas de Narcóticos/administración & dosificación , Adulto Joven
19.
Trials ; 21(1): 934, 2020 Nov 19.
Artículo en Inglés | MEDLINE | ID: mdl-33213529

RESUMEN

OBJECTIVES: Zilucoplan (complement C5 inhibitor) has profound effects on inhibiting acute lung injury post COVID-19, and can promote lung repair mechanisms that lead to improvement in lung oxygenation parameters. The purpose of this study is to investigate the efficacy and safety of Zilucoplan in improving oxygenation and short- and long-term outcome of COVID-19 patients with acute hypoxic respiratory failure. TRIAL DESIGN: This is a phase 2 academic, prospective, 2:1 randomized, open-label, multi-center interventional study. PARTICIPANTS: Adult patients (≥18y old) will be recruited at specialized COVID-19 units and ICUs at 9 Belgian hospitals. The main eligibility criteria are as follows: 1) Inclusion criteria: a. Recent (≥6 days and ≤16 days) SARS-CoV-2 infection. b. Chest CT scan showing bilateral infiltrates within the last 2 days prior to randomisation. c. Acute hypoxia (defined as PaO2/FiO2 below 350 mmHg or SpO2 below 93% on minimal 2 L/min supplemental oxygen). d. Signs of cytokine release syndrome characterized by either high serum ferritin, or high D-dimers, or high LDH or deep lymphopenia or a combination of those. 2) Exclusion criteria: e. Mechanical ventilation for more than 24 hours prior to randomisation. f. Active bacterial or fungal infection. g. History of meningococcal disease (due to the known high predisposition to invasive, often recurrent meningococcal infections of individuals deficient in components of the alternative and terminal complement pathways). INTERVENTION AND COMPARATOR: Patients in the experimental arm will receive daily 32,4 mg Zilucoplan subcutaneously and a daily IV infusion of 2g of the antibiotic ceftriaxone for 14 days (or until hospital discharge, whichever comes first) in addition to standard of care. These patients will receive additional prophylactic antibiotics until 14 days after the last Zilucoplan dose: hospitalized patients will receive a daily IV infusion of 2g of ceftriaxone, discharged patients will switch to daily 500 mg of oral ciprofloxacin. The control group will receive standard of care and a daily IV infusion of 2g of ceftriaxone for 1 week (or until hospital discharge, whichever comes first), to control for the effects of antibiotics on the clinical course of COVID-19. MAIN OUTCOMES: The primary endpoint is the improvement of oxygenation as measured by mean and/or median change from pre-treatment (day 1) to post-treatment (day 6 and 15 or at discharge, whichever comes first) in PaO2/FiO2 ratio, P(A-a)O2 gradient and a/A PO2 ratio. (PAO2= Partial alveolar pressure of oxygen, PaO2=partial arterial pressure of oxygen, FiO2=Fraction of inspired oxygen). RANDOMISATION: Patients will be randomized in a 2:1 ratio (Zilucoplan: control). Randomization will be done using an Interactive Web Response System (REDCap). BLINDING (MASKING): In this open-label trial neither participants, caregivers, nor those assessing the outcomes will be blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 81 patients will be enrolled: 54 patients will be randomized to the experimental arm and 27 patients to the control arm. TRIAL STATUS: ZILU-COV protocol Version 4.0 (June 10 2020). Participant recruitment started on June 23 2020 and is ongoing. Given the uncertainty of the pandemic, it is difficult to predict the anticipated end date. TRIAL REGISTRATION: The trial was registered on Clinical Trials.gov on May 11th, 2020 (ClinicalTrials.gov Identifier: NCT04382755 ) and on EudraCT (Identifier: 2020-002130-33 ). FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Asunto(s)
Complemento C5/antagonistas & inhibidores , Infecciones por Coronavirus/complicaciones , Hipoxia/tratamiento farmacológico , Neumonía Viral/complicaciones , Insuficiencia Respiratoria/tratamiento farmacológico , Enfermedad Aguda , Adulto , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Bélgica/epidemiología , Betacoronavirus/aislamiento & purificación , Estudios de Casos y Controles , Ceftriaxona/administración & dosificación , Ceftriaxona/uso terapéutico , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/fisiopatología , Infecciones por Coronavirus/virología , Síndrome de Liberación de Citoquinas/sangre , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Quimioterapia Combinada , Humanos , Infusiones Intravenosas , Inyecciones Subcutáneas , Oxígeno/sangre , Pandemias , Neumonía Viral/epidemiología , Neumonía Viral/fisiopatología , Neumonía Viral/virología , Estudios Prospectivos , Seguridad , Resultado del Tratamiento
20.
JAMA ; 324(19): 1948-1956, 2020 11 17.
Artículo en Inglés | MEDLINE | ID: mdl-33201202

RESUMEN

Importance: Clinical guidelines for the early management of acute heart failure in the emergency department (ED) setting are based on only moderate levels of evidence, with subsequent low adherence to these guidelines. Objective: To test the effect of an early guideline-recommended care bundle on short-term prognosis in older patients with acute heart failure in the ED. Design, Setting, and Participants: Stepped-wedge cluster randomized trial in 15 EDs in France of 503 patients 75 years and older with a diagnosis of acute heart failure in the ED from December 2018 to September 2019 and followed up for 30 days until October 2019. Interventions: A care bundle that included early intravenous nitrate boluses; management of precipitating factors, such as acute coronary syndrome, infection, or atrial fibrillation; and moderate dose of intravenous diuretics (n = 200). In the control group, patient care was left to the discretion of the treating emergency physician (n = 303). Each center was randomized to the order in which they switched to the "intervention period." After the initial 4-week control period for all centers, 1 center entered in the intervention period every 2 weeks. Main Outcomes and Measures: The primary end point was the number of days alive and out of hospital at 30 days. Secondary outcomes included 30-day all-cause mortality, 30-day cardiovascular mortality, unscheduled readmission, length of hospital stay, and kidney impairment. Results: Among 503 patients who were randomized (median age, 87 years; 298 [59%] women), 502 were analyzed. In the intervention group, patients received a median (interquartile range) of 27.0 (9-54) mg of intravenous nitrates in the first 4 hours vs 4.0 (2.0-6.0) mg in the control group (adjusted difference, 23.8 [95% CI, 13.5-34.1]). There was a significantly higher percentage of patients in the intervention group treated for their precipitating factors than in the control group (58.8% vs 31.9%; adjusted difference, 31.1% [95% CI, 14.3%-47.9%]). There was no statistically significant difference in the primary end point of the number of days alive and out of hospital at 30 days (median [interquartile range], 19 [0- 24] d in both groups; adjusted difference, -1.9 [95% CI, -6.6 to 2.8]; adjusted ratio, 0.88 [95% CI, 0.64-1.21]). At 30 days, there was no significant difference between the intervention and control groups in mortality (8.0% vs 9.7%; adjusted difference, 4.1% [95% CI, -17.2% to 25.3%]), cardiovascular mortality (5.0% vs 7.4%; adjusted difference, 2.1% [95% CI, -15.5% to 19.8%]), unscheduled readmission (14.3% vs 15.7%; adjusted difference, -1.3% [95% CI, -26.3% to 23.7%]), median length of hospital stay (8 d in both groups; adjusted difference, 2.5 [95% CI, -0.9 to 5.8]), and kidney impairment (1% in both groups). Conclusions and Relevance: Among older patients with acute heart failure, use of a guideline-based comprehensive care bundle in the ED compared with usual care did not result in a statistically significant difference in the number of days alive and out of the hospital at 30 days. Further research is needed to identify effective treatments for acute heart failure in older patients. Trial Registration: ClinicalTrials.gov Identifier: NCT03683212.


Asunto(s)
Servicio de Urgencia en Hospital , Insuficiencia Cardíaca/mortalidad , Nitratos/administración & dosificación , Paquetes de Atención al Paciente , Enfermedad Aguda , Anciano , Anciano de 80 o más Años , Diuréticos/administración & dosificación , Femenino , Francia , Furosemida/administración & dosificación , Adhesión a Directriz , Insuficiencia Cardíaca/tratamiento farmacológico , Humanos , Infusiones Intravenosas , Masculino , Alta del Paciente , Guías de Práctica Clínica como Asunto
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