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OBJECTIVES: Intravenous medication errors continue to significantly impact patient safety and outcomes. This study sought to clarify the complexity and risks of the intravenous administration process. DESIGN: A qualitative focus group interview study. SETTING: Focused interviews were conducted using process mapping with frontline nurses responsible for medication administration in September 2020. PARTICIPANTS: Front line experiened nurses from a Japanese tertiary teaching hospital. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was to identify the mental models frontline nurses used during intravenous medication administration, which influence their interactions with patients, and secondarily, to examine the medication process gaps between the mental models nurses perceive and the actual defined medication administration process. RESULTS: We found gaps between the perceived clinical administration process and the real process challenges with an emphasis on the importance of verifying to see if the drug was ordered for the patient immediately before its administration. CONCLUSIONS: This novel and applied improvement approach can help nurses and managers better understand the process vulnerability of the infusion process and develop a deeper understanding of the administration steps useful for reliably improving the safety of intravenous medications.
Assuntos
Grupos Focais , Erros de Medicação , Segurança do Paciente , Pesquisa Qualitativa , Humanos , Erros de Medicação/prevenção & controle , Erros de Medicação/estatística & dados numéricos , Erros de Medicação/enfermagem , Grupos Focais/métodos , Segurança do Paciente/normas , Segurança do Paciente/estatística & dados numéricos , Infusões Intravenosas/métodos , Percepção , Feminino , Administração Intravenosa/métodos , Adulto , Recursos Humanos de Enfermagem Hospitalar/psicologia , Recursos Humanos de Enfermagem Hospitalar/estatística & dados numéricos , Masculino , Japão , Entrevistas como Assunto/métodos , Atitude do Pessoal de SaúdeRESUMO
In 2017, a severe shortage of infusion bags resulted in a paradigm change in medication administration practice from intermittent infusion to intravenous push. The Institute for Safe Medication Practices proposed safe practice guidelines for adult intravenous push medications. A different study showed that ready-to-administer medication prepared in the sterile area of a pharmacy reduces the risk of harm, nurses' time for medication administration and the cost of medications. Based on the recommendation of the Institute for Safe Medication Practices, we decided to conduct a pilot study on the implementation of sterile compounding and administration of intravenous push medication in adult patients admitted to the hospital. In the study, the stability of five intravenous push antibiotic syringes was also determined in the syringes.
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Antibacterianos , Seringas , Centros de Atenção Terciária , Humanos , Seringas/normas , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Centros de Atenção Terciária/organização & administração , Centros de Atenção Terciária/estatística & dados numéricos , Projetos Piloto , Adulto , Administração Intravenosa/métodos , Estabilidade de Medicamentos , Infusões Intravenosas/métodos , Infusões Intravenosas/instrumentação , Infusões Intravenosas/normasRESUMO
BACKGROUND: Perioperative hypothermia is a common occurrence, particularly with the elderly and pediatric age groups. Hypothermia is associated with an increased risk of perioperative complications. One method of preventing hypothermia is warming the infused fluids given during surgery. The enFlow™ intravenous fluid warmer has recently been reintroduced with a parylene coating on its heating blocks. In this paper, we evaluated the impact of the parylene coating on the new enFlow's fluid warming capacity. METHODS: Six coated and six uncoated enFlow cartridges were used. A solution of 10% propylene glycol and 90% distilled H2O was infused into each heating cartridge at flow rates of 2, 10, 50, 150, and 200 ml/min. The infused fluid temperature was set at 4 °C, 20 °C, and 37 °C. Output temperature was recorded at each level. Data for analysis was derived from 18 runs at each flow rate (six cartridges at three temperatures). RESULTS: The parylene coated fluid warming cartridge delivered very stable output of 40 °C temperatures at flow rates of 2, 10, and 50 ml/min regardless of the temperature of the infusate. At higher flow rates, the cartridges were not able to achieve the target temperature with the colder fluid. Both cartridges performed with similar efficacy across all flow rates at all temperatures. CONCLUSIONS: At low flow rates, the parylene coated enFlow cartridges was comparable to the original uncoated cartridges. At higher flow rates, the coated and uncoated cartridges were not able to achieve the target temperature. The parylene coating on the aluminum heating blocks of the new enFlow intravenous fluid warmer does not negatively affect its performance compared to the uncoated model.
Assuntos
Administração Intravenosa/métodos , Calefação/instrumentação , Calefação/métodos , Polímeros , Xilenos , Desenho de Equipamento , Humanos , Infusões IntravenosasRESUMO
Un-complexed polynuclear ferric oxyhydroxide cannot be administered safely or effectively to patients. When polynuclear iron cores are formed with carbohydrates of various structures, stable complexes with surface carbohydrates driven by multiple interacting sites and forces are formed. These complexes deliver iron in a usable form to the body while avoiding the serious adverse effects of un-complexed forms of iron, such as polynuclear ferric oxyhydroxide. The rate and extent of plasma clearance and tissue biodistribution is variable among the commercially available iron-carbohydrate complexes and is driven principally by the surface characteristics of the complexes which dictate macrophage opsonization. The surface chemistry differences between the iron-carbohydrate complexes results in significant differences in in vivo pharmacokinetic and pharmacodynamic profiles as well as adverse event profiles, demonstrating that the entire iron-carbohydrate complex furnishes the pharmacologic action for these complex products. Currently available physicochemical characterization methods have limitations in biorelevant matrices resulting in challenges in defining critical quality attributes for surface characteristics for this class of complex nanomedicines.
Assuntos
Carboidratos/farmacologia , Carboidratos/farmacocinética , Compostos de Ferro/farmacologia , Compostos de Ferro/farmacocinética , Ferro/farmacologia , Ferro/farmacocinética , Nanopartículas/metabolismo , Administração Intravenosa/métodos , Animais , Compostos Férricos/metabolismo , HumanosRESUMO
BACKGROUND: In response to the World Health Organization call for research on alternative routes for tranexamic acid (TXA) administration in women with postpartum haemorrhage, we examined the pharmacokinetics of TXA after i.v., i.m., or oral administration. METHODS: We conducted a randomised, open-label, crossover trial in 15 healthy volunteers who received i.v. TXA 1 g, i.m. TXA 1 g, or oral TXA solution 2 g. Blood samples were drawn up to 24 h after administration. Tranexamic acid concentration was measured with liquid chromatography-mass spectrometry, and the parameters of the pharmacokinetic models were estimated using population pharmacokinetics. RESULTS: The median time to reach a concentration of 10 mg L-1 was 3.5 min for the i.m. route and 66 min for the oral route, although with the oral route the target concentration was reached in only 11 patients. Median peak concentrations were 57.5, 34.4, and 12.8 mg L-1 for i.v., i.m., and oral routes, respectively. A two-compartment open model with body weight as the main covariate best fitted the data. For a 70 kg volunteer, the population estimates were 10.1 L h-1 for elimination clearance, 15.6 L h-1 for intercompartmental clearance, 7.7 L for the volume of central compartment, and 10.8 L for the volume of the peripheral compartment. Intramuscular and oral bioavailabilities were 1.0 and 0.47, respectively, showing that i.m. absorption is fast and complete. Adverse events were mild and transient, mainly local reactions and low-intensity pain. CONCLUSIONS: The i.m. (but not oral) route appears to be an efficient alternative to i.v. tranexamic acid. Studies in pregnant women are needed to examine the impact of pregnancy on the pharmacokinetics. CLINICAL TRIAL REGISTRATION: EudraCT 2019-000285-38; NCT03777488.
Assuntos
Antifibrinolíticos/administração & dosagem , Antifibrinolíticos/farmacocinética , Ácido Tranexâmico/administração & dosagem , Ácido Tranexâmico/farmacocinética , Administração Intravenosa/métodos , Administração Oral , Adulto , Estudos Cross-Over , Feminino , Voluntários Saudáveis , Humanos , Injeções Intramusculares/métodos , Masculino , Hemorragia Pós-Parto/tratamento farmacológico , Estudos Prospectivos , Adulto JovemRESUMO
CONTEXT: Urinary tract infections (UTIs) are common in young infants, yet there is no guidance on the optimal duration of intravenous (IV) treatment. OBJECTIVE: To determine if shorter IV antibiotic courses (≤7 days) are appropriate for managing UTIs in infants aged ≤90 days. METHODS: PubMed, the Cochrane Library, Medline, and Embase (February 2021) were used as data sources. Included studies reported original data for infants aged ≤90 days with UTIs, studied short IV antibiotic durations (≤7 days), and described at least 1 treatment outcome. The Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline was followed. Studies were screened by 2 investigators, and bias was assessed by using the Newcastle-Ottawa Scale and the Revised Cochrane Risk-of-Bias Tool. RESULTS: Eighteen studies with 16 615 young infants were included. The largest 2 studies on bacteremic UTI found no difference in the rates of 30-day recurrence between those treated with ≤7 vs >7 days of IV antibiotics. For nonbacteremic UTI, there was no significant difference in the adjusted 30-day recurrence between those receiving ≤3 vs >3 days of IV antibiotics in the largest 2 studies identified. Three studies of infants aged ≥30 days used oral antibiotics alone and reported good outcomes, although only 85 infants were ≤90 days old. CONCLUSIONS: Shorter IV antibiotic courses of ≤7 days and ≤3 days with early switch to oral antibiotics should be considered in infants aged ≤90 days with bacteremic and nonbacteremic UTI, respectively, after excluding meningitis. Further studies of treatment with oral antibiotics alone are needed in this age group.
Assuntos
Administração Intravenosa/métodos , Antibacterianos/administração & dosagem , Infecções Urinárias/diagnóstico , Infecções Urinárias/tratamento farmacológico , Esquema de Medicação , Humanos , Lactente , Recém-Nascido , Resultado do Tratamento , Infecções Urinárias/sangueRESUMO
Immediate reocclusion after mechanical thrombectomy (MT) for acute ischemic stroke (AIS) is a rare but devastating condition associated with poor functional outcome. The aim of this study was to gain insights into the mechanisms underlying immediate reocclusion, and to evaluate the efficacy and safety of the glycoprotein IIb/IIIa antagonist abciximab, for its treatment. Clinical data were collected from April 2015 to April 2019 in a monocentric prospective registry of AIS patients treated by MT. All patients with immediate reocclusion were retrospectively selected and subdivided into 2 groups according to abciximab treatment status. In vitro, the separate and combined effects of abciximab and alteplase on clot formation in whole blood under flow conditions were further investigated in microfluidic chambers. From 929 MT-treated patients, 21 had post-MT immediate reocclusion. Abciximab treatment in reocclusion patients (n = 10) led to higher rate of final recanalization (p < .001) while it did not increase bleeding complications. Flow chamber experiments revealed that, in contrast to alteplase, abciximab efficiently limits thrombus accretion from flowing blood by blocking platelet aggregation. Our results underscore a key role for platelet aggregation and the potential of Glycoprotein IIb/IIIa antagonists as a rescue therapy in post-MT immediate reocclusion.
Assuntos
Abciximab/uso terapêutico , Administração Intravenosa/métodos , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/cirurgia , Inibidores da Agregação Plaquetária/uso terapêutico , Trombectomia/métodos , Abciximab/farmacologia , Doença Aguda , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/farmacologiaRESUMO
BACKGROUND: Medication dosing errors can occur during microinfusions when there is vertical pump displacement or multidrug infusion through a single intravenous path. We compared flow rate variability between new-generation cylinder-type infusion pumps and conventional infusion pumps under simulated conditions. METHODS: We evaluated the flow rates during microinfusions using different infusion pumps (syringe pump with 10/30/50-mL syringes, peristaltic pump, and cylinder pump). Two visible dyes were used as model drugs. The study samples were quantified using spectrophotometry. For vertical displacement, the infusion pumps were moved up and down by 60 cm during microinfusions at 0.5 mL·h-1 and 2 mL·h-1. In the multi-infusion study, the second drug flow was added through 4 linearly connected stopcocks either upstream or downstream of the first drug. We compared the total error dose between the cylinder pump and the syringe pump with a Mann-Whitney U test and additionally estimated the effects of the infusion pumps on total error doses by linear regression analysis. RESULTS: There were repetitive patterns of temporary flow increases when the pump was displaced upward and flow decreases when the pump was displaced downward in all settings. However, the amount of flow irregularities was more pronounced at the lower infusion rate and in the syringe-type pump using larger volume syringes. The total error dose increased in the syringe pump loaded with a 50-mL syringe compared to that of the new cylinder pump (regression coefficient [ß] = 4.66 [95% confidence interval {CI}, 1.60-7.72]; P = .008). The initiation and cessation of a new drug during multidrug microinfusion in the same intravenous path affected the lower rate first drug leading to a transient flow rate increase and decrease, respectively. The change in flow rate was observed regardless of the port selected for addition of the second drug, and the total error dose of the first drug did not significantly vary when an upstream or a downstream port was selected. CONCLUSIONS: In the microinfusion settings, attention must be paid to the use of the syringe pump loaded with large-volume syringes. The novel cylinder pump could be considered as a practical alternative to syringe pumps with small syringes given its flow stability without the need for frequent drug replacement.
Assuntos
Administração Intravenosa/instrumentação , Administração Intravenosa/métodos , Bombas de Infusão , Erros de Medicação/prevenção & controle , Seringas , Simulação por Computador , Desenho de Equipamento , Humanos , Modelos Lineares , Análise de Regressão , Reprodutibilidade dos Testes , Estatísticas não ParamétricasRESUMO
ABSTRACT: Secondary infusion by large-volume IV smart pump is used extensively in the acute care setting for one-time or intermittent administration of medications such as antibiotics, electrolyte replacements, and some oncology drugs. Consistent and accurate delivery of secondary medications requires a full understanding of the system and setup requirements. Unfortunately, it is not uncommon for nurses to find a secondary medication only partially administered when their programming should have resulted in a complete infusion. This article discusses the technical requirements that every nurse should know when administering secondary medications using an IV smart pump.
Assuntos
Administração Intravenosa/instrumentação , Administração Intravenosa/métodos , Bombas de Infusão , Segurança de Equipamentos/métodos , Segurança de Equipamentos/enfermagem , Segurança de Equipamentos/normas , HumanosRESUMO
INTRODUCTION: The catheter is the only intravascular portion of an implanted port and plays a crucial role in catheter related complications. Both polyurethane and silicone are biocompatible materials which are utilized for catheter manufacturing, but their correlation to complications remains controversial. The aim of this study was to try to analyze the relationship between catheter materials and complications. MATERIALS AND METHODS: A total of 3144 patients who underwent intravenous port implantation between March 2012 and December 2018 at Chang Gung Memorial Hospital, Linkou, Taiwan were recruited. Of these, 1226 patients received silicone catheter port implantation and 1679 received polyurethane catheter ports. Case matching was done prior to analysis and catheter related complications and cumulative complication incidence for each group were compared. RESULTS: Intergroup differences were identified in entry vessel (p = 0.0441), operation year (p < 0.0001), operation method (p = 0.0095), functional period (p < 0.0001), patient follow up status (p < 0.0001), operating time for vessel cutdown (p < 0.0001) and wire assisted approach (p = 0.0008). Stratified by specific entry vessel, no statistical difference was found in complication rate or incidence between the silicone and polyurethane groups. We further compared the cumulative complication incidence of the silicone and polyurethane groups, and also found no statistical difference (p = 0.4451). CONCLUSION: As long as external stress forces generated by surrounding structures and focused on potential weak points are avoided, both silicone and polyurethane materials provide sufficient structural stability to serve as reliable vascular access for patients.
Assuntos
Cateterismo Venoso Central/métodos , Veia Cava Superior/química , Administração Intravenosa/métodos , Cateteres de Demora , Falha de Equipamento , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Desempenho Físico Funcional , Poliuretanos/química , Silicones/química , TaiwanRESUMO
Mounting evidence indicates that vitamin C has the potential to be a potent anti-cancer agent when administered intravenously and in high doses (high-dose IVC). Early phase clinical trials have confirmed safety and indicated efficacy of IVC in eradicating tumour cells of various cancer types. In recent years, the multi-targeting effects of vitamin C were unravelled, demonstrating a role as cancer-specific, pro-oxidative cytotoxic agent, anti-cancer epigenetic regulator and immune modulator, reversing epithelial-to-mesenchymal transition, inhibiting hypoxia and oncogenic kinase signalling and boosting immune response. Moreover, high-dose IVC is powerful as an adjuvant treatment for cancer, acting synergistically with many standard (chemo-) therapies, as well as a method for mitigating the toxic side-effects of chemotherapy. Despite the rationale and ample evidence, strong clinical data and phase III studies are lacking. Therefore, there is a need for more extensive awareness of the use of this highly promising, non-toxic cancer treatment in the clinical setting. In this review, we provide an elaborate overview of pre-clinical and clinical studies using high-dose IVC as anti-cancer agent, as well as a detailed evaluation of the main known molecular mechanisms involved. A special focus is put on global molecular profiling studies in this respect. In addition, an outlook on future implications of high-dose vitamin C in cancer treatment is presented and recommendations for further research are discussed.
Assuntos
Administração Intravenosa/métodos , Ácido Ascórbico/uso terapêutico , Neoplasias/tratamento farmacológico , Ácido Ascórbico/farmacologia , HumanosRESUMO
ABSTRACT: For patients with ischemic stroke, intravenous (IV) thrombolysis with Urokinase within 6âhours has been accepted as beneficial, but its application is limited by high risk of hemorrhagic complications after thrombolysis. This study aimed to analyze the risk factors of hemorrhagic complications after intravenous thrombolysis using Urokinase in acute cerebral infarction (ACI) patients.Total 391 consecutive ACI patients were enrolled and divided into 2 groups: the hemorrhagic complications group and the non-hemorrhagic complications group. The related data were collected and analyzed.Univariate analysis showed significant differences in prothrombin time, atrial fibrillation (AF), Mean platelet volume, large platelet ratio (L-PLR), triglyceride (TG), Lactate dehydrogenase, alanine aminotransferase (ALT), high-density lipoprotein, and baseline National Institute of Health Stroke Scale score between the hemorrhagic complications and the non-hemorrhagic complications group (Pâ<â.1). Multivariate logistic regression analysis indicated that AF (odds ratio [OR]â=â2.91, 95% confidence interval [CI]â=â1.06-7.99 Pâ=â.039) was the risk factor of hemorrhagic complications, while ALT (ORâ=â0.27, 95% CIâ=â0.10-0.72 Pâ=â.009) and TG (ORâ=â0.16, 95% CIâ=â0.06-0.45 Pâ=â.000) were protective factors of hemorrhagic complications.For patients with AF and lower levels of ALT or TG, the risk of hemorrhagic complications might increase after ACI.
Assuntos
Hemorragia/etiologia , Terapia Trombolítica/efeitos adversos , Trombose/tratamento farmacológico , Administração Intravenosa/efeitos adversos , Administração Intravenosa/métodos , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Hemorragia/epidemiologia , Hemorragia/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Terapia Trombolítica/estatística & dados numéricos , Trombose/epidemiologia , Ativador de Plasminogênio Tipo Uroquinase/efeitos adversos , Ativador de Plasminogênio Tipo Uroquinase/uso terapêuticoRESUMO
RATIONALE: Studies on Candida infections in the central nervous system, especially in infants and young children that did or did not have postoperative surgery, are rarely reported. Thus far, intrathecal (i.t.) amphotericin B (AmB) is not routinely recommended as a therapy for Candida meningitis. We report the first case of Candida meningitis in an infant who underwent abdominal surgery and was successfully treated with i.t. and intravenous (i.v.) AmB in the mainland of China. PATIENT CONCERNS: Candida meningitis was confirmed by culture and immunoserological tests in a 1-day-old girl after surgery. She was treated with fluconazole for 1 month, but the patient's symptoms showed no improvement. DIAGNOSES: After surgery, the infant started having recurrent attacks of fever, and laboratory tests of the cerebrospinal fluid (CSF) revealed antigens of Candida tropicalis. CSF tests revealed a high total protein level and a low glucose level. She was diagnosed with a secondary Candida meningitis. INTERVENTIONS: After azole therapy failure, intrathecal and intravenous AmB therapy were used as rescue therapies. OUTCOMES: After nearly 2âmonths of AmB treatment, all repeat CSF cultures were negative, the infant was deemed stable and was discharged home, and she continued taking voriconazole orally as an outpatient. LESSONS: The combination of i.t. and i.v. administration of AmB can provide a safe and effective alternative to managing this rare but severe disease.
Assuntos
Anfotericina B/farmacologia , Meningite Fúngica/tratamento farmacológico , Administração Intravenosa/métodos , Anfotericina B/uso terapêutico , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida tropicalis/efeitos dos fármacos , Candida tropicalis/patogenicidade , Candidíase/tratamento farmacológico , Candidíase/fisiopatologia , China , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Feminino , Humanos , Recém-Nascido , Injeções Espinhais/métodos , Meningite Fúngica/fisiopatologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/fisiopatologiaRESUMO
Corona virus disease 2019 (COVID-19) has posed a mounting threat to public health with worldwide outbreak caused by a novel virus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Recently, remdesivir (RDV) has been approved by Food and Drug Administration (FDA) for treating COVID-19 patients ≥12 years old requiring hospitalization. To the best of our knowledge, a simple method to estimate RDV in the pharmaceutical formulations using high-performance liquid chromatography (HPLC) is still unexplored, highlighting the need for a precise analytical method for its quantification. The prime purpose of the current investigation was to develop and validate a well-grounded HPLC method for quantification of RDV in pharmaceutical formulations. The best chromatogram was obtained by means of an Inertsil ODS-3V column using a mobile phase of milli-Q water modified to pH 3.0 with o-phosphoric acid and acetonitrile (50:50, % v/v) at a flow rate of 1.2 mL/min and wavelength of detector set at 246 nm with retention time being achieved at 6.0 min. The method was validated following International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) Q2 (R1) guidelines for various parameters such as specificity and selectivity, system suitability, linearity, precision, accuracy, limits of detection and quantification, and robustness. The method developed for the quantification of RDV was found to be linear in the concentration range of 25-2,500 ng/mL with limit of detection and limit of quantification of 1.95 and 6.49 ng/mL, respectively. Assay value of 102% ± 1% was achieved for marketed injectable dosage form when estimated by the validated method. Therefore, in this study a simple, rapid, sensitive, selective, accurate, precise, and robust analytical method was developed and validated for the quantification of RDV using HPLC. The established method was successfully employed for quantification of RDV in marketed pharmaceutical formulation.
Assuntos
Monofosfato de Adenosina/análogos & derivados , Administração Intravenosa/normas , Alanina/análogos & derivados , Antivirais/administração & dosagem , Antivirais/análise , Tratamento Farmacológico da COVID-19 , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/análise , Monofosfato de Adenosina/química , Administração Intravenosa/métodos , Alanina/administração & dosagem , Alanina/análise , Alanina/química , Antivirais/química , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida de Alta Pressão/normas , Formas de Dosagem/normas , Humanos , Reprodutibilidade dos TestesRESUMO
Acute ischemic stroke patients with intravenous (IV) recombinant tissue plasminogen activator (rt-PA) thrombolysis have different outcomes. The degree of thrombolysis depends largely on the delicate balance of coagulation and fibrinolysis. Thus, our study aimed to investigate the prognostic value of routine coagulation parameters in acute stroke patients treated with rt-PA. From December 2016 to October 2018, consecutive patients treated with standard-dose IV rt-PA within 4.5â h of stroke onset were collected in Beijing Tiantan Hospital. Routine coagulation parameters, including platelet count, mean platelet volume, platelet distribution width, prothrombin time (PT), activated partial thromboplastin time, thrombin time, and fibrinogen, were measured at baseline (h0) and 24â h (h24) after thrombolysis. The change of coagulation parameters was defined as the (h24-h0)/h0 ratio. The prognosis included short-term outcome at 24â h and functional outcome at 3â months. A total of 267 patients were investigated (188 men and 79 women) with a mean age of 60.88 ± 12.31 years. In total, 9 patients had early neurological deterioration within 24â h, and 99 patients had an unfavorable outcome at the 3-month visit. In multivariate logistic regression, the (h24-h0)/h0 of PT was associated with unfavorable functional outcomes at 3â months (odds ratio: 1.42, 95% confidence interval: 1.02-2.28). While the change of other coagulation parameters failed to show any correlation with short-term or long-term prognosis. In conclusion, the prolongation of PT from baseline to 24â h after IV rt-PA increases the risk of 3-month unfavorable outcomes in acute stroke patients.
Assuntos
Administração Intravenosa/métodos , Coagulação Sanguínea/genética , AVC Isquêmico/tratamento farmacológico , Terapia Trombolítica/métodos , Ativador de Plasminogênio Tecidual/uso terapêutico , Doença Aguda , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Ativador de Plasminogênio Tecidual/farmacologiaRESUMO
Intervertebral disc (IVD) degeneration involves a complex cascade of events, including degradation of the native extracellular matrix, loss of water content, and decreased cell numbers. Cell recruitment strategies for the IVD have been increasingly explored, aiming to recruit either endogenous or transplanted cells. This study evaluates the IVD therapeutic potential of a chemoattractant delivery system (HAPSDF5) that combines a hyaluronan-based thermoreversible hydrogel (HAP) and the chemokine stromal cell derived factor-1 (SDF-1). HAPSDF5 was injected into the IVD and was combined with an intravenous injection of mesenchymal stem/stromal cells (MSCs) in a pre-clinical in vivo IVD lesion model. The local and systemic effects were evaluated two weeks after treatment. The hydrogel by itself (HAP) did not elicit any adverse effect, showing potential to be administrated by intradiscal injection. HAPSDF5 induced higher cell numbers, but no evidence of IVD regeneration was observed. MSCs systemic injection seemed to exert a role in IVD regeneration to some extent through a paracrine effect, but no synergies were observed when HAPSDF5 was combined with MSCs. Overall, this study shows that although the injection of chemoattractant hydrogels and MSC recruitment are feasible approaches for IVD, IVD regeneration using this strategy needs to be further explored before successful clinical translation.
Assuntos
Quimiocina CXCL12/uso terapêutico , Ácido Hialurônico/uso terapêutico , Degeneração do Disco Intervertebral/tratamento farmacológico , Administração Intravenosa/métodos , Animais , Regeneração Óssea/efeitos dos fármacos , Regeneração Óssea/fisiologia , Quimiocina CXCL12/administração & dosagem , Fatores Quimiotáticos/metabolismo , Modelos Animais de Doenças , Matriz Extracelular/metabolismo , Ácido Hialurônico/administração & dosagem , Hidrogéis/uso terapêutico , Disco Intervertebral/efeitos dos fármacos , Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/fisiopatologia , Masculino , Células-Tronco Mesenquimais/metabolismo , Ratos , Ratos WistarRESUMO
BACKGROUND: MVA-BN-brachyury-TRICOM is a recombinant vector-based therapeutic cancer vaccine designed to induce an immune response against brachyury. Brachyury, a transcription factor overexpressed in advanced cancers, has been associated with treatment resistance, epithelial-to-mesenchymal transition, and metastatic potential. MVA-BN-brachyury-TRICOM has demonstrated immunogenicity and safety in previous clinical trials of subcutaneously administered vaccine. Preclinical studies have suggested that intravenous administration of therapeutic vaccines can induce superior CD8+ T cell responses, higher levels of systemic cytokine release, and stronger natural killer cell activation and proliferation. This is the first-in-human study of the intravenous administration of MVA-BN-brachyury-TRICOM. METHODS: Between January 2020 and March 2021, 13 patients were treated on a phase 1, open-label, 3+3 design, dose-escalation study at the National Institutes of Health Clinical Center. The study population was adults with advanced solid tumors and was enriched for chordoma, a rare sarcoma of the notochord that overexpresses brachyury. Vaccine was administered intravenously at three DLs on days 1, 22, and 43. Blood samples were taken to assess drug pharmacokinetics and immune activation. Imaging was conducted at baseline, 1 month, and 3 months post-treatment. The primary endpoint was safety and tolerability as determined by the frequency of dose-limiting toxicities; a secondary endpoint was determination of the recommended phase 2 dose. RESULTS: No dose-limiting toxicities were observed and no serious adverse events were attributed to the vaccine. Vaccine-related toxicities were consistent with class profile (ie, influenza-like symptoms). Cytokine release syndrome up to grade 2 was observed with no adverse outcomes. Dose-effect trend was observed for fever, chills/rigor, and hypotension. Efficacy analysis of objective response rate per RECIST 1.1 at the end of study showed one patient with a partial response, four with stable disease, and eight with progressive disease. Three patients with stable disease experienced clinical benefit in the form of improvement in pain. Immune correlatives showed T cell activation against brachyury and other tumor-associated cascade antigens. CONCLUSIONS: Intravenous administration of MVA-BN-brachyury-TRICOM vaccine was safe and tolerable. Maximum tolerated dose was not reached. The maximum administered dose was 109 infectious units every 3 weeks for three doses. This dose was selected as the recommended phase 2 dose. TRIAL REGISTRATION NUMBER: NCT04134312.
Assuntos
Administração Intravenosa/métodos , Vacinas Anticâncer/uso terapêutico , Proteínas Fetais/uso terapêutico , Imunoterapia/métodos , Neoplasias/tratamento farmacológico , Proteínas com Domínio T/uso terapêutico , Vacinas Anticâncer/farmacologia , Feminino , Proteínas Fetais/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas com Domínio T/farmacologia , Vacinas Sintéticas/farmacologia , Vacinas Sintéticas/uso terapêuticoRESUMO
We assessed the feasibility and potential efficacy of a virtual reality (VR) environment using a dome screen as a distraction method in young children during intravenous (IV) placement in the pediatric emergency department. This randomized controlled pilot study enrolled children aged 2 to 6 years who underwent IV placement into either the intervention group or the control group. Children in the intervention group experienced VR using a dome screen during IV placement. The child's pain intensity was measured using the Face, Legs, Activity, Cry, and Consolability (FLACC) scale at four time points of IV placement: immediately after arrival to the blood collection room (base); immediately after the child laid down on the bed (preparation); when the tourniquet was applied (tourniquet); and the moment at which the needle penetrated the skin (venipuncture). The guardian's satisfaction and rating of the child's distress were assessed using a 5-point Likert-type questionnaire. We recruited 19 children (9 in the intervention group and 10 in the control group). Five children in the control group were excluded from the analysis because of missing video recordings (n = 3), failed first attempt at IV placement (n = 1), and the child's refusal to lie on the bed during the procedure (n = 1). No side effects of VR were reported during the study period. Although the average FLACC scale score at each time point (preparation, tourniquet, venipuncture) was lower in the intervention group than the control group, the difference was not statistically significant (2.3, interquartile range [IQR]: 2.0-3.0; vs. 3.3, IQR: 2.7-6.7, P = 0.255). There were no statistically significant differences between the groups in the guardian's satisfaction and anxiety or his/her rating of the child's pain and anxiety. The guardians and emergency medical technicians reported satisfaction with the use of VR with a dome screen and considered it a useful distraction during the procedure. VR using a dome screen is a feasible distraction method for young children during IV placement. A larger clinical trial with further development of the VR environment and study process is required to adequately evaluate the efficacy of VR using a dome screen.
Assuntos
Administração Intravenosa/métodos , Dor Processual/prevenção & controle , Realidade Virtual , Administração Intravenosa/efeitos adversos , Criança , Pré-Escolar , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Medição da Dor , Flebotomia/efeitos adversos , Flebotomia/métodos , Projetos PilotoRESUMO
PURPOSE: Postoperative pain is typically treated with multimodal analgesia, using systemic acetaminophen and/or nonsteroidal anti-inflammatory drugs in conjunction with opioids as required. The present study aimed to determine the safety and tolerability of repeated doses of an intravenous fixed-dose combination (FDC) of acetaminophen and ibuprofen. METHODS: This multicenter, open-label, single arm, multiple dose study was conducted at 4 centers across New Zealand and the United States between July 2019 and July 2020. Adults (>18 years) requiring multiple doses of parenteral nonopioid analgesics over multiple days following non-laparoscopic general, plastic or orthopedic surgery were eligible. The study drug (acetaminophen 1000 mg+ibuprofen 300 mg) was administered 6-hourly as a 5 min infusion for between 48 h and 5 days. Adverse event data was collected throughout the study, in addition to scheduled vital sign assessments, laboratory tests and electrocardiograms. Participants completed a global evaluation of the FDC at the end of the treatment period. FINDINGS: 232 participants received ≥ 1 dose of the FDC. Most were female (62.1%), White (56.5%) or Black or African American (39.2%), and had undergone orthopedic surgery (85.3%). There was a broad age range (19-87 years), with a mean age of 53.4 years, and 26.3% of participants aged ≥ 65 years. The FDC was safe when used for 48 h to 5 days. Treatment-emergent adverse events (TEAEs) affected 56.0% of participants, the most common were infusion site pain, nausea, infusion site extravasation, constipation, and headache. Minimal changes in vital signs were observed at scheduled timepoints. No clinically significant changes in electrocardiogram assessments occurred. Transient elevations in the hepatic enzymes ALT and AST to < 3 times the upper limit of normal (ULN) affected 10.5% and 9.6% of subjects, elevations to ≥ 3 times the ULN affected 2.6% and 2.2% of subjects, respectively. There were no apparent differences in the safety profile of the FDC in older participants. The FDC was well tolerated; most TEAEs were mild or moderate in severity. Five participants discontinued treatment due to TEAEs, none were considered treatment-related. The FDC was perceived well by study participants; the majority rated their experience as 'excellent' (40.1%) or 'very good' (35.3%). IMPLICATIONS: The safety profile was comparable to previous studies with no novel safety concerns. The FDC was safe, well tolerated, and perceived positively by participants treated for acute pain between 48 h and 5 days following orthopedic or plastic surgery, supporting a favorable risk benefit profile.