Comparison of arterial hypotension incidence during general anesthesia induction - target-controlled infusion vs. bolus injection of propofol: a randomized clinical trial.

BACKGROUND: The incidence of arterial hypotension during induction of general anesthesia is influenced by the method of propofol administration, but there is a dearth of randomized clinical trials comparing bolus injection and target-controlled infusion in relation to arterial hypotension. This study seeks to compare the incidence of arterial hypotension between these two methods of propofol administration. METHODS: This prospective, randomized, single-center, non-blinded study included 60 patients (aged 35 to 55 years), classified as ASA physical status I or II, who were undergoing non-cardiac surgeries. They were randomly allocated using a computer to two groups based on the method of propofol administration during the induction of general anesthesia: the Target Group, receiving target-controlled infusion at 4 µg.mL-1, and the Bolus Group, receiving a bolus infusion of 2 mg.kg-1. Both groups also received midazolam 2 mg, fentanyl 3 µg.kg-1, and rocuronium 0.6 mg.kg-1. Over the first 10 minutes of anesthesia induction, Mean Arterial Pressure (MAP), Heart Rate (HR), level of Consciousness (qCON), and Suppression Rate (SR) were recorded every 2 minutes. RESULTS: Twenty-seven patients remained in the TCI group, while 28 were in the Bolus group. Repeated measure analysis using mixed-effects models could not reject the null hypothesis for the effect of group-time interactions in MAP (p = 0.85), HR (p = 0.49), SR (p = 0.44), or qCON (p = 0.72). The difference in means for qCON (60.2 for TCI, 50.5 for bolus, p < 0.001), MAP (90.3 for TCI, 86.2 for bolus, p < 0.006), HR (76.2 for TCI, 76.9 for bolus, p = 0.93), and SR (0.01 for TCI, 5.5 for bolus, p < 0.001), irrespective of time (whole period means), revealed some significant differences. CONCLUSION: Patients who received propofol bolus injection exhibited a lower mean arterial pressure, a greater variation in the level of consciousness, and a higher suppression rate compared to those who received it as a target-controlled infusion. However, the interaction effect between groups and time remains inconclusive.

Uso de hierro intravenoso en el tratamiento de la anemia ferropénica en niños: a propósito de un caso / Use of intravenous iron for the treatment of iron deficiency anemia in children: clinical case study / Uso de ferro intravenoso no tratamento da anemia ferropriva em crianças: relato de caso

Introducción: el déficit de hierro es la causa más común de anemia debido a carencia nutricional. Su tratamiento consiste en proporcionar alimentos ricos en hierro biodisponible junto con la administración de hierro oral. En circunstancias definidas puede utilizarse el hierro intravenoso. Objetivo: describir el abordaje diagnóstico y terapéutico de un niño portador de anemia ferropénica severa secundaria a mala adherencia al hierro oral en el que se utilizó hierro intravenoso. Caso clínico: niño de 21 meses, raza blanca. Antecedente de anemia ferropénica severa, con repercusión hemodinámica que a los 14 meses requirió transfusión de sangre desplasmatizada. Sin controles de hemoglobina posteriores. Sin adherencia a profilaxis con hierro vía oral. Alto consumo de leche de vaca y bajo consumo de alimentos ricos en hierro. En el contexto de infección respiratoria aguda baja se constata anemia clínica con marcado decaimiento y anorexia, sin repercusión hemodinámica. Se confirma la anemia microcítica, hipocrómica severa, con ancho de distribución eritrocitaria elevado, con metabolismo de hierro alterado. Recibe hierro sacarato, intravenoso, por seis días con buena tolerancia y evolución. Discusión: se identificaron múltiples factores de riesgo para anemia ferropénica. La pobre respuesta al tratamiento con hierro oral debido a efectos adversos y olvidos de administración, junto al antecedente de anemia ferropénica severa, que requirió transfusión de sangre desplasmatizada, motivaron la indicación de hierro intravenoso. Su administración fue programada y monitorizada, sin complicaciones. Es necesario fortalecer la prevención en todos los controles pediátricos y abordar este problema de salud desde una mirada interdisciplinaria.

Introduction: iron deficiency is the most common cause of anemia due to nutritional deficiency. Its treatment consists of providing bioavailable iron rich food together with oral iron. In specific circumstances, intravenous iron may be used. Objective: of this study is to describe the diagnostic and therapeutic approach used with a child with severe iron deficiency anemia secondary to poor adherence to oral iron, in which intravenous iron was used. Clinical case: 21 month-old white patient. History of severe iron deficiency anemia, with hemodynamic repercussions that at 14 months of age required transfusion of deplasmatized blood. Without subsequent hemoglobin controls. No adherence to oral iron prophylaxis. High consumption of cow's milk and low of iron-rich foods. Within the context of acute lower respiratory infection, a clinical anemia with marked decline and anorexia were observed, without hemodynamic repercussions. Severe hypochromic microcytic anemia was confirmed, with an elevated erythrocyte distribution width and altered iron metabolism. He received iron saccharate, intravenously for 6 days with good tolerance and evolution. Discussion: multiple risk factors for iron deficiency anemia were identified. The poor response to treatment with oral iron resulting from adverse effects and lack of proper administration, together with a history of severe iron deficiency anemia, which required transfusion of deplasmatized blood, led to the prescription of intravenous iron. This administration was scheduled and monitored, occurring without complications. It is necessary to strengthen prevention of this condition in all pediatric check-ups and address this health problem from an interdisciplinary perspective.

Introdução: a deficiência de ferro é a causa mais comum de anemia por deficiência nutricional. Seu tratamento consiste no fornecimento de alimentos ricos em ferro biodisponível, juntamente com a administração de ferro por via oral. Em circunstâncias especificas, pode ser utilizado ferro intravenoso. Objetivo: descrever a abordagem diagnóstica e terapêutica de uma criança com anemia ferropriva grave secundária a sua má adesão ao ferro oral, e o uso de ferro intravenoso. Caso clínico: 21 meses, raça branca. História de anemia ferropriva grave, com repercussão hemodinâmica que requiriu de transfusão de sangue desplasmatizada aos 14 meses. Não houve nenhum controle de hemoglobina subsequente. Nenhuma adesão à profilaxia oral com ferro. Alto consumo de leite de vaca e baixo consumo de alimentos ricos em ferro. No contexto de infecção respiratória inferior aguda, observa-se anemia clínica com acentuado emagrecimento e anorexia, sem repercussões hemodinâmicas. É confirmada anemia microcítica e hipocrômica grave, com largura de distribuição eritrocitária elevada e metabolismo alterado do ferro. Recebeu sacarose férrica intravenosa por 6 dias com boa tolerância e evolução. Discussão: foram identificados múltiplos fatores de risco para anemia ferropriva. A má resposta ao tratamento com ferro oral devido aos efeitos adversos e ao esquecimento da administração, aliás da história de anemia ferropriva grave, que exigiu transfusão de sangue desplasmatizada, motivaram a indicação do ferro intravenoso. Sua administração foi programada e monitorada, e aconteceu sem intercorrências. É preciso fortalecer a prevenção em todos os controles pediátricos e abordar este problema de saúde numa persectiva interdisciplinar.

Delayed onset, immunomodulation, and lifespan improvement of SOD1G93A mice after intravenous injection of human mesenchymal stem cells derived from adipose tissue.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the selective and progressive loss of motor neurons from the spinal cord, brain stem, and motor cortex. Although the hallmark of ALS is motor neuron degeneration, astrocytes, microglia, and T cells actively participate. Pharmacological treatment with riluzole has little effect on the lifespan of the patient. Thus, the development of new therapeutic strategies is of utmost importance. The objective of this study was to verify whether human mesenchymal stem cells (hMSCs) from adipose tissue have therapeutic potential in SOD1G93A transgenic mice. The treatment was carried out in the asymptomatic phase of the disease (10th week) by a single systemic application of ad-hMSCs (1 ×105 cells). The animals were sacrificed at the 14th week (the initial stage of symptoms) or the end-stage (ES) of the disease. The lumbar spinal cords were dissected and processed for Nissl staining (neuronal survival), immunohistochemistry (gliosis and synaptic preservation), and gene transcript expression (qRT-PCR). Behavioral analyses considering the onset of disease and its progression, neurological score, body weight, and motor control (rotarod test) started on the 10th week and were performed every three days until the ES of the disease. The results revealed that treatment with ad-hMSCs promoted greater neuronal survival (44%) than vehicle treatment. However, no effect was seen at the ES of the disease. Better structural preservation of the ventral horn in animals treated with ad-hMSCs was observed, together with decreased gliosis and greater synapse protection. In line with this, we found that the transcript levels of Hgf1 were upregulated in ad-hMSCs-treated mice. These results corroborate the behavioral data showing that ad-hMSCs had delayed motor deficits and reduced weight loss compared to vehicle animals. Additionally, cell therapy delayed the course of the disease and significantly improved survival by 20 days. Overall, our results indicate that treatment with ad-hMSCs has beneficial effects, enhancing neuronal survival and promoting a less degenerative neuronal microenvironment. Thus, this may be a potential therapy to improve the quality of life and to extend the lifespan of ALS patients.

Atención odontológica bajo sedación endovenosa (R2) en niños hospitalizados con enfermedades respiratorias crónicas / Dental care under intravenous sedation in children hospitalized with chronic respiratory diseases

RESUMEN: El Hospital Josefina Martínez está especializado en atención de niños con enfermedades respiratorias crónicas. En él hemos implementado un modelo de atención odontológica, bajo sedación endovenosa, monitorización cardiorespiratoria con participación de un equipo multidisciplinario. Objetivos: Describir la atención odontológica en pacientes hospitalizados con enfermedades respiratorias crónicas. Identificar las patologías bucales más prevalentes y los tratamientos realizados. Material y Método: El estudio se realizó incluyendo las atenciones odontológicas bajo sedación endovenosa, entre los años 2014-2016, considerando a 18 pacientes hospitalizados. Todos recibieron sedación y analgesia con Midazolam-Ketamina con monitorización continua no invasiva durante el procedimiento. Resultados: Se encontró una alta prevalencia de gingivitis, anomalías dentomaxilares y patologías de erupción. La lesión de caries tuvo baja prevalencia. Los tratamientos realizados fueron: profilaxis, destartarje, aplicación de barniz de clorhexidina y/o flúor, exodoncias, exposición quirúrgica de dientes y restauraciones. Conclusiones: Es importante mostrar nuestra experiencia, ya que hemos realizado tratamientos en forma oportuna, eficiente y de bajo costo, mejorando la salud bucal de los niños. Además fueron atendidos sin necesitar traslado a otro centro de salud, permitiendo resolver las urgencias y la atención odontológica integral de los pacientes.

ABSTRACT: The Josefina Martínez Hospital specializes in the care of children with chronic respiratory diseases. There, we implemented a model of dental care under intravenous sedation and cardiorespiratory monitoring, with the participation of a multidisciplinary team. Objective: Describe dental care in hospitalized patients with chronic respiratory diseases. Identify the most prevalent oral diseases and the treatments performed. Materials and Methodology: The study was conducted including dental care under intravenous sedation, between 2014 and 2016, considering 18 hospitalized patients. All received sedation and analgesia with Midazolam-Ketamine with continuous non-invasive monitoring during the procedure. Results: A high prevalence of gingivitis, dentomaxillary abnormalities and eruption disorders was found. Caries lesion had a low prevalence. The treatments performed were: prophylaxis, scaling, application of chlorhexidine and / or fluoride varnish, extractions, surgical exposure of teeth and restorations. Conclusion: It is important to show our experience, since we have made timely, efficient and low cost treatments, improving the oral health of children. In addition, they were attended without requiring the transfer to other health centers, which allowed to meet the emergencies and the comprehensive dental care of the patients.

Acute Limb Ischemia After Self-Injection of Crushed Morphine Tablets into the Radial Artery: Role of Infrared Thermography in the Assessment of Tissue Perfusion.

BACKGROUND This article presents a case involving complications after intentional injection of crushed tablets into the arterial circulation, its diagnosis, and the treatment adopted. The diagnosis process illustrates the potential of techniques based on thermal imaging as tools to assess tissue perfusion. Inadvertent intravenous injection of crushed tablets is more common, but there are few reports on arterial circulation, and no studies were found on the self-injection of crushed morphine tablets, particularly into the radial artery. CASE REPORT A 51-year-old man with alcoholism and a history of illegal drug usage intentionally self-injected 3 crushed morphine tablets into his right radial artery. The patient progressed with compartment syndrome, requiring decompressive fasciotomy of the right forearm and ischemia of the right fingers, which were amputated. He presented with rhabdomyolysis and required dialysis. The patient agreed to full heparinization, corticotherapy, and the use of nitroglycerin and prostaglandin E1. Due to the progression of the necrotic area, the patient underwent proximal phalanx excision and surgical reconstruction of the right-hand remnant. CONCLUSIONS The injection of morphine tablets into circulation caused severe complications, which led to the excision of the proximal phalanx and the surgical reconstruction of the remnant of the right hand. In the present case, infrared thermography proved to be an effective method in assessing tissue perfusion.

Uso da realidade virtual durante a punção venosa em crianças hospitalizadas: estudo descritivo / Use of virtual reality during venipuncture procedures in hospitalized children: a descriptive study / Uso de realidad virtual durante la venopunción en niños hospitalizados: estudio descriptivo

OBJETIVO: Descrever o uso da realidade virtual durante a punção venosa em crianças hospitalizadas. MÉTODO: Estudo descritivo, de abordagem quantitativa, realizado por meio de observação da punção venosa em crianças em uso de óculos de realidade virtual, em uma unidade de internação pediátrica de um hospital da região noroeste do Paraná. Os dados foram coletados no período de agosto a setembro de 2019. RESULTADOS: Foram observadas 16 crianças com idades entre quatro e oito anos que receberam o procedimento concomitante ao uso dos óculos. Os escores de dor foram predominantemente leves em ambas as faixas etárias e o comportamento psicotomotor mais evidenciado foi um desconforto pequeno. CONCLUSÃO: O estudo demonstrou que as punções realizadas com o uso da realidade virtual apresentaram escores de dor leves e no tangente ao manejo da dor, seu uso pode ser uma alternativa benéfica dentro da assistência pediátrica na realização de procedimentos dolorosos.

OBJECTIVE: To describe the use of Virtual Reality during venipuncture procedures in hospitalized children. METHOD: A descriptive study with a quantitative approach, carried out through observation of venipuncture procedures in children using Virtual Reality glasses at a pediatric inpatient unit of a hospital in the Northwest region of Paraná. The data were collected from August to September 2019. RESULTS: A total of 16 children were observed, aged between four and eight years old and who were subjected to the procedure along with use of the glasses. The pain scores were predominantly mild in both age groups and the most evident psychomotor behavior was minor discomfort. CONCLUSION: The study showed that the punctures performed using Virtual Reality presented mild pain scores and that, in terms of pain management, its use can be a beneficial alternative within pediatric care in the performance of painful procedures.

OBJETIVO: Describir el uso de la realidad virtual durante la venopunción en niños hospitalizados. MÉTODO: Estudio descriptivo, con enfoque cuantitativo, realizado mediante la observación de la venopunción en niños que usaban lentes de realidad virtual, en una unidad de hospitalización pediátrica de un hospital en la región noroeste de Paraná. Los datos se recolectaron de agosto a septiembre de 2019. RESULTADOS: se observaron 16 niños de cuatro a ocho años que recibieron el procedimiento concomitantemente con el uso de lentes. En ambas franjas etarias predominaron los puntajes de dolor leves y el comportamiento psicomotor más evidente fue el malestar leve. CONCLUSIÓN: El estudio demostró que las punciones realizadas durante el uso de realidad virtual presentaron puntajes de dolor leve y en lo que respecta al manejo del dolor, su uso puede ser una alternativa beneficiosa dentro de la atención pediátrica en la realización de procedimientos dolorosos.

Development of fluorescent- and radio-traceable T1307-polymeric micelles as biomedical agents for cancer diagnosis: biodistribution on 4T1 tumor-bearing mice

Abstract In recent years, nanocarriers have been studied as promising pharmaceutical tools for controlled drug-delivery, treatment-efficacy follow-up and disease imaging. Among them, X-shaped amphiphilic polymeric micelles (Tetronic®, poloxamines) display great potential due to their biocompatibility and non-toxic effects, among others. In the present work, polymeric micelles based on the T1307 copolymer were initially decorated with a 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY)-fluorophore in order to determinate its in vivo biodistribution on 4T1 tumor-bearing mice. However, unfavorable results with this probe led to two different strategies. On the one hand, the BODIPY-micelle-loaded, L-T1307-BODIPY, and on the other hand, the 99mTc-micelle-radiolabeled, L-T1307- 99m Tc, were analyzed separately in vivo. The results indicated that T1307 accumulates mainly in the stomach, the kidneys, the lungs and the tumor, reaching the maximum organ-accumulation 2 hours after intravenous injection. Additionally, and according to the results obtained for L-T1307- 99m Tc, the capture of the polymeric micelles in organs could be observed up to 24 hours after injection. The results obtained in this work were promising towards the development of new radiotracer agents for breast cancer based on X-shaped polymeric micelles.

Effects of exogenous ghrelin on the tissue structure and somato-statin secretion in the pancreas of African ostrich chicks / Efectos de la grelina exógena en la estructura del tejido y la secreción de somato-estatinas en el páncreas de los polluelos de avestruz africanos

SUMMARY: This study aimed to investigate the effect of exogenous ghrelin on pancreatic growth and development in African ostrich chicks. Sixteen 40-day-old African ostrich chicks (male or female) were randomly divided into four groups and injected intravenously metatarsal vein with saline (control) or ghrelin (10, 50, and 100 μg/kg) for 6 days. Body and pancreas weight were determined, structural characteristics were observed using HE staining, somatostatin-immunopositive cells were detected using immunohistochemistry. The results were as follows: 1. The 50 and 100 μg/kg groups showed lower relative pancreas weight than the control group (P 0.05. Moreover, compared with the control, the islet cells in treatment groups were loosely arranged and showed reduced cytoplasm. In the exocrine pancreas, the volume of acinar cells in the 10, 50, and 100 μg/kg groups all decreased to varying degrees. 3. Somatostatin immunopositive cells were mainly located around the periphery of the islets and sporadically distributed in the center. The density of the somatostatin immunopositive cells in the 10, 50, and 100 μg/kg groups was higher than that in the control (P < 0.05). These findings suggest that exogenous ghrelin increases the area and number of islets and number of somatostatin immunopositive cells but reduces relative pancreas weight and effects the morphological and structural development of the pancreas, which may inhibit the pancreatic growth and development in African ostrich chicks.

RESUMEN: Este estudio tuvo como objetivo investigar el efecto de la grelina exógena sobre el crecimiento y desarrollo del páncreas en polluelos de avestruz africana. Dieciséis pollos de avestruz africana de 40 días (machos o hembras) se dividieron al azar en cuatro grupos y se inyectaron por vía intravenosa con solución salina (control) o grelina (10, 50 y 100 μg / kg) durante 6 días. determinadas, se observaron las características estructurales mediante tinción Hematoxilina-Eosina, se detectaron células inmunopositivas a somatostatina mediante inmunohistoquímica. Los resultados fueron los siguientes: ¨Los grupos de 50 y 100 μg / kg mostraron un menor peso relativo del páncreas que el grupo de control (P <0,05). El área de islotes por unidad de área del páncreas fue mayor en los grupos de 10, 50 y 100 μg / kg grupos que en el grupo de control (P <0,05). El número de islotes por unidad de área del páncreas fue menor en el grupo de 10 μg / kg que en el control (P <0,05). Además, en comparación con el control, las células de los islotes en los grupos de tratamiento estaban dispuestas de forma holgada y mostraban un citoplasma reducido. En el páncreas exocrino, el volumen de células acinares en los grupos de 10, 50 y 100 μg / kg disminuyó en diversos grados. Las células inmunopositivas de somatostatina se ubicaron principalmente alrededor de la periferia de los islotes y se distribuyeron esporádicamente en el centro. La densidad de las células inmunopositivas a la somatostatina en los grupos de 10, 50 y 100 μg / kg fue mayor que la del control (P <0,05). Estos hallazgos sugieren que la grelina exógena aumenta el área y el número de islotes y el número de células inmunopositivas a la somatostatina, pero reduce el peso relativo del páncreas, lo que puede inhibir el crecimiento y desarrollo pancreático en los polluelos de avestruz africana.

Magnesium sulfate vs aminophylline as a second line of treatment in children with severe acute asthma. Randomized clinical trial. / Sulfato de magnesio vs aminofilina como segunda línea de manejo en niños con asma aguda severa. Ensayo clínico aleatorizado.

INTRODUCTION: Second-line drugs for acute asthma, such as salbutamol, magnesium sulfate, and aminophylline, are generally intravenously administered. OBJECTIVE: To compare the efficacy and safety of using mag nesium sulfate or aminophylline in children who did not respond to initial treatment. PATIENTS AND METHOD: Randomized clinical trial. Children who did not improve the Modified Pulmonary Index Score (mPSI) receive at random magnesium sulfate (50 mg/kg/single dose) or aminophylline (5 mg/ kg/dose followed by continuous infusion at 1 mg/kg/hour for 3 hours). Primary endpoints were changes in mPSI and oxygen saturation; secondary endpoints: hospitalization rate, need for transfer to the intensive care unit, use of a third intervention, and adverse effects. RESULTS: 131 patients were studied (66 patients in the aminophylline group and 65 MgSO4). The mean age was 5 ± 2.3 years, the demographic and clinical parameters did not differ between the groups. In the group that received magnesium sulfate, the mPSI and oxygen saturation changed significantly in favor from 13.1 ± 1.3 to 4.9 ± 2.5 (p < 0.001) and from 3.3 ± 2.5; (p 0.021), respectively, and their risk of hospital admission (RR 0.68 95% CI [0.56, 0.82]) and of secondary failure (0.16 95% CI 95% [0 , 07; 0.38]) decreased. Only one adverse event (tachycardia) was recorded. CONCLUSION: The administration of a single dose of magnesium sulfate proved to be more effective and safe than the use of aminophylline as a second- line drug.

Copper biodistribution after acute systemic administration of copper gluconate to rats.

Neurodegenerative disorders have been linked to the decrease of copper concentrations in different regions of the brain. Therefore, intake of micronutrient supplements could be a therapeutic alternative. Since the copper distribution profile has not been elucidated yet, the aim of this study was to characterize and to analyze the concentration profile of a single administration of copper gluconate to rats by two routes of administration. Male Wistar rats were divided into three groups. The control group received vehicle (n = 5), and the experimental groups received 79.5 mg/kg of copper orally (n = 4-6) or 0.64 mg/kg of copper intravenously. (n = 3-4). Blood, striatum, midbrain and liver samples were collected at different times. Copper concentrations were assessed using atomic absorption spectrophotometry. Copper concentration in samples from the control group were considered as baseline. The highest copper concentration in plasma was observed at 1.5 h after oral administration, while copper was quickly compartmentalized within the first hour after intravenous administration. The striatum evidenced a maximum metal concentration at 0.25 h for both routes of administration, however, the midbrain did not show any change. The highest concentration of the metal was held by the liver. The use of copper salts as replacement therapy should consider its rapid and discrete accumulation into the brain and the rapid and massive distribution of the metal into the liver for both oral and intravenous routes. Development of controlled-release pharmaceutical formulations may overcome the problems that the liver accumulation may imply, particularly, for hepatic copper toxicity.

Pharmacologic Restraint Use During Mental Health Visits in Pediatric Emergency Departments.

OBJECTIVES: To evaluate the trends and hospital variation in the use of pharmacologic restraint among pediatric mental health visits in the emergency department (ED). STUDY DESIGN: We examined ED visits with a mental health diagnosis in patients aged 3-21 years at children's hospital EDs from 2009 to 2019. We calculated the frequency of pharmacologic restraint use and determined visit characteristics associated with restraint use. We calculated cumulative percent change for visits with restraints and for all mental health visits. We used logistic regression to test trends over time and evaluate hospital variation in the frequency of restraint use. RESULTS: We identified 389 885 mental health ED visits (54.9% female, median age 14.3 years) and 13 643 (3.5%) visits with pharmacologic restraint use. Characteristics associated with pharmacologic restraint use were late adolescent age (18-21 years), male sex, Black race, non-Latino ethnicity, public insurance, and admission to the hospital (P < .001). During the study period, both mental health ED visits increased by 268% and mental health ED visits with pharmacologic restraint use increased by 370%. The rate of pharmacologic restraint in this patient population remained constant. Hospital use of pharmacologic restraint for mental health visits varied significantly across hospitals (1.6%-11.8%, P < .001). CONCLUSIONS: Pediatric mental health ED visits with and without pharmacologic restraint are increasing over time. In addition, the overall number of pharmacologic restraint use has increased threefold. Significant hospital variation in pharmacologic restraint use signifies an opportunity for standardization of care and restraint reduction.

Helmet mask and tocilizumab for a patient with hemophagocytic lymphohistiocytosis syndrome and COVID-19: a case report.

The management of acute hypoxemic respiratory failure and the effect of antiviral drugs in patients with severe COVID-19 have been debated. This case presents the management of a 64-year-old man COVID-19 patient admitted to the Intensive Care Unit with fever, fatigue, shortness of breath and hemophagocytic lymphohistiocytosis syndrome. Helmet mask was successfully used to treat his hypoxemic respiratory failure without any aerosol problems. Tocilizumab, an antagonist interleukin-6, was intravenously infused as an alternative drug. After administration, the high level of IL-6, CRP, ferritin, D-dimer, triglyceride, and H-scores decreased, and the patient observed good clinical and laboratory improvements. In this case report, we describe the effect of noninvasive ventilation delivered by helmet mask and antiviral drugs, and the intravenous administration of tocilizumab in a patient with hemophagocytic lymphohistiocytosis syndrome and COVID-19.

Evaluation of the efficacy and safety of icatibant and C1 esterase/kallikrein inhibitor in severe COVID-19: study protocol for a three-armed randomized controlled trial.

BACKGROUND: SARS-CoV-2, the virus that causes COVID-19, enters the cells through a mechanism dependent on its binding to angiotensin-converting enzyme 2 (ACE2), a protein highly expressed in the lungs. The putative viral-induced inhibition of ACE2 could result in the defective degradation of bradykinin, a potent inflammatory substance. We hypothesize that increased bradykinin in the lungs is an important mechanism driving the development of pneumonia and respiratory failure in COVID-19. METHODS: This is a phase II, single-center, three-armed parallel-group, open-label, active control superiority randomized clinical trial. One hundred eighty eligible patients will be randomly assigned in a 1:1:1 ratio to receive either the inhibitor of C1e/kallikrein 20 U/kg intravenously on day 1 and day 4 plus standard care; or icatibant 30 mg subcutaneously, three doses/day for 4 days plus standard care; or standard care alone, as recommended in the clinical trials published to date, which includes supplemental oxygen, non-invasive and invasive ventilation, antibiotic agents, anti-inflammatory agents, prophylactic antithrombotic therapy, vasopressor support, and renal replacement therapy. DISCUSSION: Accumulation of bradykinin in the lungs is a common side effect of ACE inhibitors leading to cough. In animal models, the inactivation of ACE2 leads to severe acute pneumonitis in response to lipopolysaccharide (LPS), and the inhibition of bradykinin almost completely restores the lung structure. We believe that inhibition of bradykinin in severe COVID-19 patients could reduce the lung inflammatory response, impacting positively on the severity of disease and mortality rates. TRIAL REGISTRATION: Brazilian Clinical Trials Registry Universal Trial Number (UTN) U1111-1250-1843. Registered on May/5/2020.

Recombinant human C1 esterase inhibitor (conestat alfa) in the prevention of severe SARS-CoV-2 infection in hospitalized patients with COVID-19: A structured summary of a study protocol for a randomized, parallel-group, open-label, multi-center pilot trial (PROTECT-COVID-19).

OBJECTIVES: Conestat alfa, a recombinant human C1 esterase inhibitor, is a multi-target inhibitor of inflammatory cascades including the complement, the kinin-kallikrein and the contact activation system. The study objective is to investigate the efficacy and safety of conestat alfa in improving disease severity and short-term outcome in COVID-19 patients with pulmonary disease. TRIAL DESIGN: This study is an investigator-initiated, randomized (2:1 ratio), open-label, parallel-group, controlled, multi-center, phase 2a clinical trial. PARTICIPANTS: This trial is conducted in 3 hospitals in Switzerland, 1 hospital in Brazil and 1 hospital in Mexico (academic and non-academic). All patients with confirmed SARS-CoV-2 infection requiring hospitalization for at least 3 calendar days for severe COVID-19 will be screened for study eligibility. INCLUSION CRITERIA: - Signed informed consent - Age 18-85 years - Evidence of pulmonary involvement on CT scan or X-ray of the chest - Duration of symptoms associated with COVID-19 ≤ 10 days - At least one of the following risk factors for progression to mechanical ventilation on the day of enrolment: 1) Arterial hypertension 2) ≥ 50 years 3) Obesity (BMI ≥ 30 kg/m2) 4) History of cardiovascular disease 5) Chronic pulmonary disease 6) Chronic renal disease 7) C-reactive protein > 35mg/L 8) Oxygen saturation at rest of ≤ 94% when breathing ambient air Exclusion criteria: - Incapacity or inability to provide informed consent - Contraindications to the class of drugs under investigation (C1 esterase inhibitor) - Treatment with tocilizumab or another IL-6R or IL-6 inhibitor before enrolment - History or suspicion of allergy to rabbits - Pregnancy or breast feeding - Active or anticipated treatment with any other complement inhibitor - Liver cirrhosis (any Child-Pugh score) - Admission to an ICU on the day or anticipated within the next 24 hours of enrolment - Invasive or non-invasive ventilation - Participation in another study with any investigational drug within the 30 days prior to enrolment - Enrolment of the study investigators, their family members, employees and other closely related or dependent persons INTERVENTION AND COMPARATOR: Patients randomized to the experimental arm will receive conestat alfa in addition to standard of care (SOC). Conestat alfa (8400 U followed by 4200 U every 8 hours) will be administered as a slow intravenous injection (5-10 minutes) over a 72-hour period (i.e. 9 administrations in total). The first conestat alfa treatment will be administered on the day of enrolment. The control group will receive SOC only. SOC treatment will be administered according to local institutional guidelines, including supplemental oxygen, antibiotics, corticosteroids, remdesivir, and anticoagulation. MAIN OUTCOMES: The primary endpoint of this trial is disease severity on day 7 after enrolment assessed by an adapted WHO Ordinal Scale for Clinical Improvement (score 0 will be omitted and score 6 and 7 will be combined) from 1 (no limitation of activities) to 7 (death). Secondary outcomes include (i) the time to clinical improvement (time from randomization to an improvement of two points on the WHO ordinal scale or discharge from hospital) within 14 days after enrolment, (ii) the proportion of participants alive and not having required invasive or non-invasive ventilation at 14 days after enrolment and (iii) the proportion of subjects without an acute lung injury (defined by PaO2/FiO2 ratio of ≤300mmHg) within 14 days after enrolment. Exploratory outcomes include virological clearance, C1 esterase inhibitor pharmacokinetics and changes in routine laboratory parameters and inflammatory proteins. RANDOMISATION: Subjects will be randomised in a 2:1 ratio to treatment with conestat alfa in addition to SOC or SOC only. Randomization is performed via an interactive web response system (SecuTrial®). BLINDING (MASKING): In this open-label trial, participants, caregivers and outcome assessors are not blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): We will randomise approximately 120 individuals (80 in the active treatment arm, 40 in the SOC group). Two interim analyses after 40 and 80 patients are planned according to the Pocock adjusted levels αp = 0.0221. The results of the interim analysis will allow adjustment of the sample size (Lehmacher, Wassmer, 1999). TRIAL STATUS: PROTECT-COVID-19 protocol version 3.0 (July 07 2020). Participant recruitment started on July 30 2020 in one center (Basel, Switzerland, first participant included on August 06 2020). In four of five study centers patients are actively recruited. Participation of the fifth study center (Mexico) is anticipated by mid December 2020. Completion of trial recruitment depends on the development of the SARS-CoV-2 pandemic. TRIAL REGISTRATION: Clinicaltrials.gov, number: NCT04414631 , registered on 4 June 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of 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.

Comparative pharmacokinetics and pharmacokinetic/pharmacodynamic analysis by nonlinear mixed-effects modeling of cefquinome in nonpregnant, pregnant, and lactating goats after intravenous and intramuscular administration.

Cefquinome is a fourth-generation cephalosporin that is used empirically in goats. Different physiologic factors like pregnancy or lactation could determine the pharmacokinetic behavior of drugs in the organism. The objectives of this study are to (a) compare the pharmacokinetics of cefquinome after intravenous and intramuscular administration in adult nonpregnant (n = 6), pregnant (n = 6), and lactating goats (n = 6), at a dose of 2 mg/kg, with rich sampling by nonlinear mixed-effects modeling, (b) conduct a pharmacokinetic/pharmacodynamic analysis to evaluate the efficacy of the recommended posology in goats with different physiological states, and (c) determine the optimal posology that achieve a PTA value ≥ 90%, taking into account a T > MIC ≥ 60% of a MIC value ≤ 0.25 µg/ml, in the different subpopulations of goats for both routes. Gestation significantly increased Ka and V1, while reduced F0, Cl, and Q. On the other hand, lactation significantly increased V1 and reduced Tk0. Cefquinome concentrations achieved in placental cotyledon, amniotic fluid, and fetal serum indicate a minimal penetration across the placental barrier. Moreover, milk penetration of cefquinome was minimal. The total body clearance of cefquinome for goats was 0.29 L kg-1  hr-1 , that is apparently higher than the reported for cows (0.13 L kg-1  hr-1 ) and pigs (0.16 L kg-1  hr-1 ). So, the optimal dose regimen for cefquinome after intravenous and intramuscular administration required higher dose and frequency of administration compared with recommendations for cows or pigs. Therefore, 2 mg kg-1  8 hr-1 and 5 mg kg-1  12 hr-1 could be used for IV and IM routes, respectively, for the treatment of respiratory infections caused by P. multocida and M. haemolytica, but only 5 mg kg-1  12 hr-1 by both routes should be recommended for Escherichia coli infections.

Percepção da criança hospitalizada acerca do brinquedo terapêutico instrucional na terapia intravenosa / Percepción del niño hospitalizado acerca del juguete terapéutico instructivo en la terapia intravenosa / Perception of the hospitalized child about the instructional therapeutic play in intravenous therapy

Resumo Objetivo analisar a percepção da criança hospitalizada quanto ao uso do brinquedo terapêutico instrucional no preparo para a terapia intravenosa. Método estudo descritivo, com abordagem qualitativa, realizado em um hospital pediátrico público no município de Juazeiro do Norte - Ceará, entre os meses de julho a setembro de 2019. Participaram do estudo 31 crianças em idade pré-escolar e escolar. Os dados foram coletados por meio de uma entrevista semiestruturada e, posteriormente, analisados por meio do software IRAMUTEQ. Resultados diante da percepção das crianças acerca da terapia intravenosa, foi averiguado que elas compreenderam a técnica a partir da utilização do brinquedo terapêutico instrucional. Quando a criança tem a oportunidade de brincar e dramatizar a terapia intravenosa, por meio do brinquedo terapêutico instrucional, a ansiedade, a dor, a angústia, a solidão, o medo e o choro são atenuados. Conclusões e implicações para a prática orientar as crianças quanto à realização da terapia intravenosa favorece sua compreensão quanto aos reais benefícios desta técnica para a sua saúde, possibilitando, ainda, a compreensão do enfermeiro quanto às condições que representam riscos para a criança e intervenha em tempo hábil por meio da utilização de estratégias que favoreçam a recuperação da saúde e a minimização de traumas subsequentes advindos da hospitalização.

Resumen Objetivo Analizar la percepción del niño hospitalizado cuanto al uso del juguete terapéutico instructivo en la preparación para la terapia intravenosa. Método Estudio descriptivo, con enfoque cualitativo, realizado en un hospital pediátrico público de la ciudad de Juazeiro do Norte - Ceará, entre julio y septiembre de 2019. Participaron 31 niños en edad preescolar y escolar. Los datos se recogieron mediante entrevista semiestructurada, posteriormente analizados con el software IRAMUTEQ. Resultados En vista de la percepción de los niños acerca de la terapia intravenosa, se encontró que ellos comprendieron la técnica a partir del uso del juguete terapéutico instructivo. Cuando tienen la oportunidad de jugar y dramatizar la terapia intravenosa, a través del juguete terapéutico instructivo, la ansiedad, el dolor, la angustia, la soledad, el miedo y el llanto son mitigados. Conclusiones e implicaciones para la práctica Orientar a los niños sobre la realización de la terapia intravenosa favorece su comprensión sobre los beneficios reales de esta técnica para su salud, permitiendo además que la enfermera comprenda las condiciones que suponen riesgos para el niño e intervenga de forma oportuna, mediante el uso de estrategias que favorezcan la recuperación de la salud y la minimización de traumas posteriores a la hospitalización.

Abstract Objective to analyze the perception of the hospitalized child regarding the use of the instructional therapeutic play in preparation for intravenous therapy. Method descriptive study, with a qualitative approach, performed in a public pediatric hospital in the city of Juazeiro do Norte - Ceará, between the months of July and September 2019. A total of 31 pre-school and school children participated in the study. The data were collected through a semi-structured interview, and later analyzed through IRAMUTEQ software. Results in view of the children's perception of intravenous therapy, it was found that they understood the technique, from the use of the instructional therapeutic play. When the child has the opportunity to play and dramatize intravenous therapy, through the instructional therapeutic play, the anxiety, the pain, the anguish, the loneliness, the fear and the crying are mitigated. Conclusion and implications for practice Orienting children in the performance of intravenous therapy favors their understanding of the real benefits of this technique for their health, allowing the nurse to understand the conditions that pose risks to the child, and intervene in a timely manner, through the use of strategies that favor the recovery of health and the minimization of subsequent trauma from hospitalization.