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2.
BMJ Open ; 11(9): e047788, 2021 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-34497079

RESUMO

OBJECTIVES: Infants in neonatal units benefit from dependable peripheral intravenous access. However, peripheral intravenous access exposes infants to high rates of clinically minor and serious complications. Despite this, little is known about the interplay of risk factors. The aim of this study was to assess the incidence and evaluate the interactions of risk factors on the occurrence of peripheral intravenous complications in a neonatal population. DESIGN: This was a retrospective observational study. SETTING: The study was performed on the neonatal intensive care unit of the Women's Wellness and Research Center, Hamad Medical Corporation, Qatar, as a single-site study. PARTICIPANTS: This study included 12 978 neonates who required intravenous therapy. OUTCOME MEASUREMENTS: The main outcome was the occurrence of any peripheral intravenous cannulation failure, leading to unplanned removal of the device before completion of the intended intravenous therapy. RESULTS: A mean dwell time of 36±28 hours was recorded in participants with no complications, whereas the mean dwell time was 31±23 hours in participants with an indication for premature removal of the peripheral intravenous catheter (PIVC) (p<0.001, t=11.35). Unplanned removal occurred in 59% of cases; the overall complication rate was 18 per 1000 catheter days. Unmodifiable factors affecting PIVC dwell time include lower birth (HR=0.23, 0.20 to 0.28, p<0.001) and current body weight (HR=1.06, 1.03 to 1.10, p=0.018). Cannulation site (HR=1.23, 1.16 to 1.30, p<0.001), the inserted device (HR=0.89, 0.84 to 0.94, p<0.001) and the indication for intravenous treatment (HR=0.76, 0.73 to 0.79, p<0.001) were modifiable factors. CONCLUSION: Most infants experienced a vascular access-related complication. Given the high complication rate, PIVCs should be used judiciously and thought given prior to their use as to whether alternate means of intravenous access might be more appropriate.


Assuntos
Cateterismo Periférico , Remoção de Dispositivo , Administração Intravenosa , Cateterismo Periférico/efeitos adversos , Feminino , Humanos , Lactente , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Estudos Retrospectivos
3.
BMC Musculoskelet Disord ; 22(1): 703, 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404381

RESUMO

BACKGROUND: The administration of an intra-articular injection (IAI) of tranexamic acid (TXA) has been demonstrated to be effective in reducing both blood loss and transfusion rate during total knee arthroplasty (TKA); however, few studies have reported the efficiency of a peri-articular injection (PAI) of TXA. We studied the efficiency of a PAI of TXA in reducing blood loss during TKA. METHODS: Fifty patients undergoing primary simultaneous bilateral TKA were enrolled in this retrospective study. The right knee received a PAI of 1 g of TXA (Group I), and the left knee received an IAI of 1 g of TXA (Group II). The clinical outcome measures were a change in blood loss from Hemovac drains and surgical time. RESULTS: The decrease in blood loss from the Hemovac was significantly lower in Group I (460.1 ± 36.79 vs. 576.0 ± 34.01, P < 0.001) than in Group II, and no significant difference in surgical times was observed. The blood transfusion rate in the present study was 16 %. CONCLUSIONS: A PAI of TXA may reduce blood loss more efficiently than an IAI of TXA during TKA without increased complications such as surgical site infection, poor wound healing, skin necrosis, pulmonary embolism, and deep vein thrombosis.


Assuntos
Antifibrinolíticos , Artroplastia do Joelho , Ácido Tranexâmico , Administração Intravenosa , Antifibrinolíticos/uso terapêutico , Artroplastia do Joelho/efeitos adversos , Perda Sanguínea Cirúrgica/prevenção & controle , Humanos , Injeções Intra-Articulares , Hemorragia Pós-Operatória/induzido quimicamente , Hemorragia Pós-Operatória/prevenção & controle , Estudos Retrospectivos
4.
Viruses ; 13(8)2021 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-34452371

RESUMO

Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the susceptibility of animals and their potential to act as reservoirs or intermediate hosts for the virus has been of significant interest. Pigs are susceptible to multiple coronaviruses and have been used as an animal model for other human infectious diseases. Research groups have experimentally challenged swine with human SARS-CoV-2 isolates with results suggesting limited to no viral replication. For this study, a SARS-CoV-2 isolate obtained from a tiger which is identical to human SARS-CoV-2 isolates detected in New York City and contains the D614G S mutation was utilized for inoculation. Pigs were challenged via intravenous, intratracheal, or intranasal routes of inoculation (n = 4/route). No pigs developed clinical signs, but at least one pig in each group had one or more PCR positive nasal/oral swabs or rectal swabs after inoculation. All pigs in the intravenous group developed a transient neutralizing antibody titer, but only three other challenged pigs developed titers greater than 1:8. No gross or histologic changes were observed in tissue samples collected at necropsy. In addition, no PCR positive samples were positive by virus isolation. Inoculated animals were unable to transmit virus to naïve contact animals. The data from this experiment as well as from other laboratories supports that swine are not likely to play a role in the epidemiology and spread of SARS-CoV-2.


Assuntos
COVID-19/virologia , SARS-CoV-2/fisiologia , Administração Intranasal , Administração Intravenosa , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , COVID-19/sangue , COVID-19/imunologia , Modelos Animais de Doenças , Humanos , Boca/virologia , Nariz/virologia , SARS-CoV-2/genética , Suínos , Traqueia/virologia , Replicação Viral
5.
Int J Mol Sci ; 22(16)2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34445399

RESUMO

Iron oxide nanoparticles and single domain antibodies from camelids (VHHs) have been increasingly recognized for their potential uses for medical diagnosis and treatment. However, there have been relatively few detailed characterizations of their pharmacokinetics (PK). The aim of this study was to develop imaging methods and pharmacokinetic models to aid the future development of a novel family of brain MRI molecular contrast agents. An efficient near-infrared (NIR) imaging method was established to monitor VHH and VHH conjugated nanoparticle kinetics in mice using a hybrid approach: kinetics in blood were assessed by direct sampling, and kinetics in kidney, liver, and brain were assessed by serial in vivo NIR imaging. These studies were performed under "basal" circumstances in which the VHH constructs and VHH-conjugated nanoparticles do not substantially interact with targets nor cross the blood brain barrier. Using this approach, we constructed a five-compartment PK model that fits the data well for single VHHs, engineered VHH trimers, and iron oxide nanoparticles conjugated to VHH trimers. The establishment of the feasibility of these methods lays a foundation for future PK studies of candidate brain MRI molecular contrast agents.


Assuntos
Camelídeos Americanos/imunologia , Rim/química , Fígado/química , Nanopartículas Magnéticas de Óxido de Ferro/química , Anticorpos de Domínio Único/administração & dosagem , Administração Intravenosa , Animais , Química Encefálica , Feminino , Fluorometria , Humanos , Camundongos , Modelos Teóricos , Tamanho da Partícula , Anticorpos de Domínio Único/sangue , Anticorpos de Domínio Único/química
7.
Medicine (Baltimore) ; 100(29): e26769, 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34398056

RESUMO

ABSTRACT: There is evidence for ketamine use in treatment-resistant depression (TRD). Several safety and tolerability concerns arise regarding adverse drug reactions and specific subpopulations. This paper aims to investigate the relationship between dissociative and psychometric measures in course of intravenous ketamine treatment in TRD inpatients with major depressive disorder and bipolar disorder.This study result represents safety data in a population of 49 inpatients with major depressive disorder and bipolar disorder subjects receiving eight 0.5 mg/kg of ketamine intravenous infusions, with a duration of 40 min each, as an add-on treatment to standard-of-care pharmacotherapy, registered in the naturalistic observational protocol of the tertiary reference unit for mood disorders (NCT04226963). The safety psychometrics assessed dissociation and psychomimetic symptomatology with the Clinician-Administered Dissociative States Scale (CADSS) the Brief Psychiatric Rating Scale (BPRS).The significant differences in CADSS scores between measurements in course of the treatment were observed (P = .003). No significant differences between BPRS measurements were made after infusions. In each case, both BPRS and CADSS values dropped to the "absent" level within 1 hour from the infusion. Neither CADSS nor BPRS scores were associated with the treatment outcome.The study demonstrates a good safety profile of intravenous ketamine as an add-on intervention to current psychotropic medication in TRD. The abatement of dissociation was observed in time with no sequelae nor harm. The study provides no support for the association between dissociation and treatment outcome.This study may be underpowered due to the small sample size. The protocol was defined as a study on acute depressive symptomatology without blinding.


Assuntos
Anestésicos Dissociativos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Ketamina/uso terapêutico , Administração Intravenosa , Adolescente , Adulto , Idoso , Anestésicos Dissociativos/administração & dosagem , Transtornos Dissociativos , Feminino , Humanos , Ketamina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Resultado do Tratamento , Adulto Jovem
8.
Lancet ; 398(10301): 665-674, 2021 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-34388396

RESUMO

BACKGROUND: There is a need for novel therapies for relapsed or refractory multiple myeloma, and B-cell maturation antigen (BCMA) is a validated target. Teclistamab is a bispecific antibody that binds BCMA and CD3 to redirect T cells to multiple myeloma cells. The aim of the MajesTEC-1 study was to evaluate the safety, tolerability, and preliminary efficacy of teclistamab in patients with relapsed or refractory multiple myeloma. METHODS: This open-label, single-arm, phase 1 study enrolled patients with multiple myeloma who were relapsed, refractory, or intolerant to established therapies. Teclistamab was administered intravenously (range 0·3-19·2 µg/kg [once every 2 weeks] or 19·2-720 µg/kg [once per week]) or subcutaneously (range 80-3000 µg/kg [once per week]) in different cohorts, with step-up dosing for 38·4 µg/kg or higher doses. The primary objectives were to identify the recommended phase 2 dose (part one) and characterise teclistamab safety and tolerability at the recommended phase 2 dose (part two). Safety was assessed in all patients treated with at least one dose of teclistamab. Efficacy was analysed in response-evaluable patients (ie, patients who received at least one dose of teclistamab and had at least one post-baseline response evaluation). This ongoing trial is registered with ClinicalTrials.gov, NCT03145181. FINDINGS: Between June 8, 2017, and March 29, 2021, 219 patients were screened for study inclusion, and 157 patients (median six previous therapy lines) were enrolled and received at least one dose of teclistamab (intravenous n=84; subcutaneous n=73). 40 patients were administered the recommended phase 2 dose, identified as once per week subcutaneous administration of teclistamab at 1500 µg/kg, after 60 µg/kg and 300 µg/kg step-up doses (median follow-up 6·1 months, IQR 3·6-8·2). There were no dose-limiting toxicities at the recommended phase 2 dose in part one. In the 40 patients treated at the recommended phase 2 dose, the most common treatment-emergent adverse events were cytokine release syndrome in 28 (70%; all grade 1 or 2 events) and neutropenia in 26 (65%) patients (grade 3 or 4 in 16 [40%]). The overall response rate in response-evaluable patients treated at the recommended phase 2 dose (n=40) was 65% (95% CI 48-79); 58% achieved a very good partial response or better. At the recommended phase 2 dose, the median duration of response was not reached. 22 (85%) of 26 responders were alive and continuing treatment after 7·1 months' median follow-up (IQR 5·1-9·1). At the recommended phase 2 dose, teclistamab exposure was maintained above target exposure levels, and consistent T-cell activation was reported. INTERPRETATION: Teclistamab is a novel treatment approach for relapsed or refractory multiple myeloma. At the recommended phase 2 dose, teclistamab showed promising efficacy, with durable responses that deepened over time, and was well tolerated, supporting further clinical development. FUNDING: Janssen Research & Development.


Assuntos
Anticorpos Biespecíficos , Antineoplásicos Imunológicos/uso terapêutico , Antígeno de Maturação de Linfócitos B/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Administração Intravenosa , Idoso , Anticorpos Biespecíficos/farmacologia , Anticorpos Monoclonais Humanizados/administração & dosagem , Antígeno de Maturação de Linfócitos B/imunologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Resultado do Tratamento
9.
BMC Musculoskelet Disord ; 22(1): 675, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376180

RESUMO

BACKGROUND: This study aimed to assess the efficacy of tranexamic acid (TXA) mixed in a periarticular multimodal cocktail (PAMC) as a topical administration and to determine whether combined use of intravenous and topical administration is more effective than a single administration of TXA. METHODS: A total of 240 patients who underwent primary total knee arthroplasty (TKA) was enrolled for this prospective randomized controlled study. Patients were divided into three groups of 80 patients each. Baseline data were comparable for all groups. Average follow-up was 18.7 months. Group 1 consisted of patients who received intravenous (IV) TXA, Group 2 patients were those who received TXA in a PAMC injection for topical administration, and Group 3 consisted of patients who received a combination of both intravenous and topical administration of TXA. Primary outcomes were postoperative hemoglobin drop and amount of suction drainage. Secondary outcomes were estimated blood loss (EBL), postoperative transfusion rate, and complications. RESULTS: The mean postoperative hemoglobin drop was significantly lower in Group 3 (2.13 ± 0.77 g/dL, p=0.004), and there was no difference between Group 1 and Group 2 (2.56 ± 1.07 g/dL vs 2.55 ± 0.86 g/dL, p=0.999). The mean drainage amount was significantly lower in Group 3 (326.58 ± 57.55 ml, p<0.001), and there was no difference between Group 1 and Group 2 (367.93 ± 87.26 ml vs 397.66 ± 104.10 ml, p=0.072). Similarly, the mean EBL was significantly lower in Group 3 (p=0.003), and there was no significant difference between Group 1 and Group 2 (p=0.992). There were no significant differences in requirement for postoperative transfusion rate or incidence of complications among the three groups. CONCLUSION: TXA mixed in a PAMC injection showed a similar effect to IV administration of TXA following TKA. Furthermore, combined use of both IV and PAMC injection provided better perioperative bleeding control with similar safety in patients without relevant comorbidities. TRIAL REGISTRATION: WHO ICTRP identifier KCT0005703 . Retrospectively registered: 12/24/2020.


Assuntos
Antifibrinolíticos , Artroplastia do Joelho , Ácido Tranexâmico , Administração Intravenosa , Administração Tópica , Antifibrinolíticos/uso terapêutico , Artroplastia do Joelho/efeitos adversos , Perda Sanguínea Cirúrgica/prevenção & controle , Humanos , Estudos Prospectivos
10.
BMC Musculoskelet Disord ; 22(1): 663, 2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34372818

RESUMO

BACKGROUND: To indicate whether combined topical and intravenous (IV) administration of tranexamic acid (TXA) could further reduce the blood loss after surgery for adolescent idiopathic scoliosis (AIS) compared with IV-TXA alone. METHODS: Ninety AIS patients who underwent posterior spinal fusion were prospectively randomized to combined group (IV + topical- TXA group) and IV-TXA alone group. TXA was infused at a loading dose of 1 g from the beginning of the surgery with a maintenance dose of 10 mg/kg/h until the wound was closed. In the combined group, 2 g TXA was injected retrogradely through a drain, while an equivalent amount of normal saline was injected in the IV-TXA alone group. The drain tube was clamped for 2 h in both groups. The amount of wound drainage and transfusion rates were analyzed. RESULTS: The drainage volume and duration of drain were significantly lower in the combined group compared with that in the IV-TXA alone group (372.0 ± 129.7 mL vs. 545.2 ± 207.7 mL, P < 0.001;64.7 ± 13.9 h vs. 82.0 ± 12.5 h, P < 0.001). Postoperative length of hospital stay was also significantly shorter in the combined group (6.5 ± 1.51 days vs. 7.95 ± 1.44 days, P < 0.05). Transfusion and complication rates were comparable between the two groups . CONCLUSIONS: IV injection of TXA combined with retrograde injection of TXA into a drain and clamping it for 2 h could further reduce the total volume of drainage in AIS patients who underwent spinal fusion surgery. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR1900024177 , Registered 29 June 2019, http://www.chictr.org.cn/showproj.aspx?proj=40214.


Assuntos
Antifibrinolíticos , Escoliose , Fusão Vertebral , Ácido Tranexâmico , Administração Intravenosa , Administração Tópica , Adolescente , Antifibrinolíticos/efeitos adversos , Perda Sanguínea Cirúrgica/prevenção & controle , Humanos , Hemorragia Pós-Operatória/etiologia , Hemorragia Pós-Operatória/prevenção & controle , Escoliose/cirurgia , Fusão Vertebral/efeitos adversos , Ácido Tranexâmico/efeitos adversos
11.
Commun Biol ; 4(1): 956, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34381159

RESUMO

Lipid Nanoparticles (LNPs) are used to deliver siRNA and COVID-19 mRNA vaccines. The main factor known to determine their delivery efficiency is the pKa of the LNP containing an ionizable lipid. Herein, we report a method that can predict the LNP pKa from the structure of the ionizable lipid. We used theoretical, NMR, fluorescent-dye binding, and electrophoretic mobility methods to comprehensively measure protonation of both the ionizable lipid and the formulated LNP. The pKa of the ionizable lipid was 2-3 units higher than the pKa of the LNP primarily due to proton solvation energy differences between the LNP and aqueous medium. We exploited these results to explain a wide range of delivery efficiencies in vitro and in vivo for intramuscular (IM) and intravascular (IV) administration of different ionizable lipids at escalating ionizable lipid-to-mRNA ratios in the LNP. In addition, we determined that more negatively charged LNPs exhibit higher off-target systemic expression of mRNA in the liver following IM administration. This undesirable systemic off-target expression of mRNA-LNP vaccines could be minimized through appropriate design of the ionizable lipid and LNP.


Assuntos
Expressão Gênica , Íons/química , Lipídeos/química , Nanopartículas/química , RNA Mensageiro/química , RNA Mensageiro/genética , Administração Intravenosa , Animais , Composição de Medicamentos , Humanos , Concentração de Íons de Hidrogênio , Injeções Intramusculares , Camundongos , Estrutura Molecular , Nanopartículas/ultraestrutura , RNA Mensageiro/administração & dosagem , RNA Mensageiro/farmacocinética , Análise Espectral , Distribuição Tecidual , Transfecção
12.
J Am Vet Med Assoc ; 259(3): 283-287, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34242075

RESUMO

OBJECTIVE: To prospectively compare the effectiveness and any adverse effects of apomorphine administered SC or IV for induction of emesis in dogs. ANIMALS: 42 client-owned dogs. PROCEDURES: Dogs for which emesis induction was deemed appropriate by the attending clinician were prospectively randomized to receive apomorphine (0.03 mg/kg [0.01 mg/lb]) either SC (n = 20) or IV (22). Data collected included whether emesis was successfully induced, time from drug administration to emesis, number of emetic events, and adverse events (eg, sedation, protracted vomiting, or other). RESULTS: Of the 20 dogs given apomorphine SC, 16 (80%) vomited. Of the 22 dogs given apomorphine IV, 18 (82%) vomited. With regard to route of administration, the number of dogs in which emesis was induced did not differ significantly. Median time to the first emetic event was 13.5 minutes (range, 3 to 32 minutes) in the SC treatment group and 2 minutes (range, 1 to 5 minutes) in the IV treatment group; the difference was significant. There was no significant difference in the number of emetic events or frequency of adverse events between the 2 groups. CONCLUSIONS AND CLINICAL RELEVANCE: Apomorphine administered SC or IV reliably induced emesis in dogs. Compared with SC administration of apomorphine, the time from drug administration to emesis associated with IV administration was significantly shorter, a finding that has clinical importance.


Assuntos
Apomorfina , Vômito , Administração Intravenosa/veterinária , Animais , Apomorfina/efeitos adversos , Cães , Eméticos/efeitos adversos , Vômito/induzido quimicamente , Vômito/veterinária
13.
Clin Interv Aging ; 16: 1265-1274, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34262266

RESUMO

Purpose: Elderly people represent a growing stroke population with different pathophysiological states than younger. Whether intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) is beneficial for elderly patients remains unclear. This study compared the efficacy and safety between elderly patients treated with MT alone and those treated with both IVT and MT. Patients and Methods: Patients aged ≥65 years who were eligible for IVT within 4.5 h from symptom onset were selected from the ANGEL-ACT (Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemic Stroke) registry, a prospective registry program for patients with endovascular treatment from 111 Chinese stroke centers. The primary efficacy outcome was the 90-day modified Rankin Scale score. We compared efficacy and safety outcomes using ordinal or binary logistic regression or a generalized linear model. Results: In total, 482 elderly patients were included: 187 (38.8%) received IVT and MT (bridging MT) and 295 (61.2%) received MT alone (direct MT). There was no significant difference in the 90-day modified Rankin Scale score between the two groups (median: 4 vs 4 points, respectively; adjusted ß=-0.048, P=0.822). The direct MT group had a shorter onset-to-puncture time (225 vs 255 min, respectively; adjusted ß=-55.074, P=0.002) and a lower rate of parenchymal hemorrhage type 2 within 24 h (2.80% vs 6.63%, respectively; adjusted odds ratio [OR]=0.287, 95% confidence interval [CI]=0.096-0.856, P=0.025). In addition, the direct MT group showed a trend toward a lower incidence of sICH (5.67% vs 10.06%, adjusted OR=0.453, P=0.061), procedure-related complications (7.12% vs 12.30%, adjusted OR=0.499, P=0.052) and distal or new territorial embolization (4.07% vs 6.95%, adjusted OR=0.450, P=0.093). Conclusion: Direct MT had similar efficacy to bridging MT in terms of the 90-day functional outcome in elderly patients, whereas bridging MT had a longer onset-to-puncture time and increased risk of hemorrhagic transformation and procedure-related complications.


Assuntos
Hemorragia Cerebral , Transtornos Cerebrovasculares , AVC Isquêmico , Trombectomia , Administração Intravenosa , Idoso , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/etiologia , Transtornos Cerebrovasculares/complicações , Transtornos Cerebrovasculares/diagnóstico , Transtornos Cerebrovasculares/terapia , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/etiologia , AVC Isquêmico/cirurgia , Masculino , Avaliação de Processos e Resultados em Cuidados de Saúde , Melhoria de Qualidade , Trombectomia/efeitos adversos , Trombectomia/métodos , Terapia Trombolítica/métodos , Fluxo de Trabalho
14.
Nano Lett ; 21(14): 6289-6297, 2021 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-34232048

RESUMO

Mild testicular hyperthermia by the photothermal effect of gold nanorods could realize controllable male contraception. However, associated limitations, such as testicular administration and infrared laser inflicting severe pain, and the nondegradability of nanoparticles potentially causing toxicity, have restricted further clinical application. Inspired by the excellent physicochemical properties of iron oxide nanoparticles (IONPs), and the finding that testicular injection of PEG-coated IONPs with a diameter of 50 nm (PEG@Fe3O4-50) following an alternating magnetic field (AMF) could achieve controllable male contraception; here we propose a noninvasive, targeting approach for male contraception via intravenous administration. The magnetic properties and testes targeting of IONPs were proven to be greatly affected by their surface chemistry and particle size. After systemic administration, citric acid stabilized IONPs with size of 100 nm (CA@Fe3O4-100) were found to be the best ideal thermoagent for realizing the noninvasive contraception. This study offers new strategies for male contraception.


Assuntos
Hipertermia Induzida , Nanopartículas de Magnetita , Administração Intravenosa , Anticoncepção , Humanos , Hipertermia , Campos Magnéticos , Masculino , Testículo
15.
J Pediatr Orthop ; 41(8): e686-e691, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34231541

RESUMO

BACKGROUND: This study aimed to investigate the effect of intravenous tranexamic acid (TXA) on blood loss and transfusion rates in children who underwent resection and endoprosthetic reconstruction of distal femoral osteosarcomas. METHODS: The medical records of 56 patients who underwent resection and endoprosthetic reconstruction for distal femoral osteosarcomas between 2017 and 2019 were retrospectively reviewed. Patients were divided into 2 groups: group 1 consisted of 25 patients (11 male and 14 female, mean age 15.2±3 y) who received preoperative 15 mg/kg intravenous TXA, and group 2 consisted of 31 control patients (18 male and 13 female, mean age 14.3±2.6 y) who did not receive TXA. The groups were compared based on their total blood loss, intraoperative blood loss, hidden blood loss, postoperative drain output, transfusion requirements, preoperative and postoperative hemoglobin (Hb) and hematocrit (Htc) difference, length of hospital stays, operative time, and complications. RESULTS: The mean total blood loss was lower in intravenous TXA group (1247.5±300.9 mL) when compared with control group (1715.7±857.0 mL) (P=0.018). The mean intraoperative blood loss in intravenous TXA group (386±109 mL) was lower than that in control group (977.4±610.7 mL) (P<0.001). Postoperative drain output at 24 and 48 hours was 198.0±61.8 and 72.4±27.4 mL in intravenous TXA group, respectively, and was low compared with 268.4±118.2 and 117.1±67.8 mL in control group (P=0.028 and 0.006). The rate of patients requiring transfusion was significantly lower in intravenous TXA group (56%) than in control group (83.9%). Preoperative and postoperative 6, 24, and 72 hours Hb and Htc differences were significantly lower in intravenous TXA group [(-1.7±1.8 g/dL P<0.001; -2.0±1.5 g/dL P<0.001; -2.3±1.7 g/dL P<0.001, for Hb) (-5.7±4.6, P<0.001; -6.9±4.0, P<0.001; -9.6±9.1, P<0.001, for Htc)]. Intravenous TXA group had shorter hospital stay time in comparison to control group (P<0.001). The operative time was significantly longer in the control group (P<0.05). No increase in pulmonary embolism or venous thromboembolism rate was observed with intravenous TXA use. CONCLUSION: We conclude that administration of intravenous TXA reduces intraoperative and postoperative blood loss, transfusion rates, and hospital stay in resection and endoprosthetic reconstruction of the distal femoral osteosarcomas in children. TYPE OF STUDY: This was a retrospective comparative study. LEVEL OF EVIDENCE: Level III.


Assuntos
Antifibrinolíticos , Osteossarcoma , Ácido Tranexâmico , Administração Intravenosa , Adolescente , Perda Sanguínea Cirúrgica/prevenção & controle , Criança , Feminino , Humanos , Masculino , Osteossarcoma/cirurgia , Estudos Retrospectivos
16.
J Neurol Sci ; 427: 117557, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34214920

RESUMO

BACKGROUND: There is contradicting evidence on the outcome of emergency patients treated during weekends versus weekdays. We studied if outcome of ischemic stroke patients receiving intravenous thrombolysis (IVT) differs according to the treatment time. METHODS: Our retrospective study included consecutive patients receiving IVT within 4.5 h of stroke onset between June 1995 and December 2018 at the Helsinki University Hospital. The patients were compared based on the treatment initiation either during weekdays (Monday to Friday) or weekend (Saturday and Sunday). The primary outcome was 3-month mortality and secondary outcomes comprised 3-month modified Rankin Scale (mRS) and incidence of symptomatic intracerebral hemorrhage (sICH). Additional analyses studied the effect of IVT treatment according to non-office hours, time of day, and season. RESULTS: Of the 3980 IVT-treated patients, 28.0% received treatment during weekends. Mortality was similar after weekend (10.0%) and weekday (10.6%) admissions in the multivariable regression analysis (OR 0.78; 95% CI 0.59-1.03). Neither 3-month mRS (OR 0.98; 95% CI 0.86-1.12), nor the occurrence of sICH (4.2% vs 4.6%; OR 0.87; 95% CI 0.60-1.26) differed between the groups. No outcome difference was observed between the office vs non-office hours or by the time of day. However, odds for worse outcome were higher during autumn (OR 1.19; 95% CI 1.04-1.35) and winter (OR 1.15; 95% CI 1.01-1.30). CONCLUSION: We did not discover any weekend effect for IVT-treated stroke patients. This confirms that with standardized procedures, an equal quality of care can be provided to patients requiring urgent treatment irrespective of time.


Assuntos
Isquemia Encefálica , Acidente Vascular Cerebral , Administração Intravenosa , Isquemia Encefálica/complicações , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/epidemiologia , Hemorragia Cerebral/tratamento farmacológico , Hemorragia Cerebral/epidemiologia , Fibrinolíticos/uso terapêutico , Humanos , Estudos Retrospectivos , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/epidemiologia , Terapia Trombolítica , Fatores de Tempo , Resultado do Tratamento
17.
Eur J Pharm Sci ; 165: 105928, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34265405

RESUMO

Conjugation with polyethylene glycol (PEG), PEGylation, has been considered a useful tool to improve drug-like properties of novel small molecules and biologics in drug discovery. PEG40 or 40 kDa PEG is a double-branched PEG, routinely employed to improve the pharmacokinetics (PK) of therapeutics, including successful marketed products such as Pegasys® and Omontys®. However, less is known about the extent of contribution of PEG40 to the overall PK of the PEGylated product. Considering the half-life of PEG40 conjugated PEGylated products ranges from 1 to 14 days in human, this information is immensely valuable. After successfully developing a high sensitivity NMR based analytical method to quantitate PEG40 in mice serum after intravenous (IV) administration (Khandelwal et al., 2019), here, we extend its application to measure PEG40 in serum after IV administration and subcutaneous (SC) absorption in routinely employed non-clinical species in drug discovery, namely, mice, rats and cynomolgus monkeys. We utilized non-compartmental analysis and compartmental modeling to characterize the PK of PEG40 in these non-clinical species. Finally, we employed allometric scaling and Wajima (MRT-Css) method to predict the PK of PEG40 in human after IV administration and SC absorption. In general, our data shows that intrinsic PK parameters of PEG40 in mice, rats and cynomolgus monkeys are in the range of published literature values for PEG40-conjugated products, unless saturable clearance mechanisms are involved. We observed a bioavailability (F) of ~68% in CD-1 mice after SC administration of PEG40. In rats, the clearance (CL) and volume of distribution at steady state (Vss) after IV infusion of PEG40 were 0.079 mL/min/kg and 0.19 L/kg, respectively; and SC bioavailability was ~20%. In cynomolgus monkeys, after IV infusion, CL and Vss of PEG40 were 0.037 mL/min/kg and 0.20 L/kg, respectively; and SC bioavailability was ~69%. In addition, our findings indicate flip-flop kinetics of PEG40 in rodents, but not in cynomolgus monkeys. Finally, in human, intrinsic CL and Vss of PEG40 were projected to be 0.02 mL/min/kg (0.084 L/h) and 0.22 L/kg, respectively. This comprehensive report of PK of PEG40 in non-clinical species and its subsequent prediction in humans is expected to be useful to drug discovery and development scientists for efficient decision-making and optimal resource utilization.


Assuntos
Polietilenoglicóis , Administração Intravenosa , Animais , Disponibilidade Biológica , Meia-Vida , Humanos , Macaca fascicularis , Camundongos , Ratos
18.
Life Sci Alliance ; 4(9)2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34321327

RESUMO

The use of high-dose of intravenous immunoglobulins (IVIGs) as immunomodulators for the treatment of COVID-19-affected individuals has shown promising results. IVIG reduced inflammation in these patients, who progressively restored respiratory function. However, little is known about how they may modulate immune responses in COVID-19 individuals. Here, we have analyzed the levels of 41 inflammatory biomarkers in plasma samples obtained at day 0 (pretreatment initiation), 3, 7, and 14 from five hospitalized COVID-19 patients treated with a 5-d course of 400 mg/kg/d of IVIG. The plasmatic levels of several cytokines (Tumor Necrosis Factor, IL-10, IL-5, and IL-7), chemokines (macrophage inflammatory protein-1α), growth/tissue repairing factors (hepatic growth factor), complement activation (C5a), and intestinal damage such as Fatty acid-binding protein 2 and LPS-binding protein showed a progressive decreasing trend during the next 2 wk after treatment initiation. This trend was not observed in IVIG-untreated COVID-19 patients. Thus, the administration of high-dose IVIG to hospitalized COVID-19 patients may improve their clinical evolution by modulating their hyperinflammatory and immunosuppressive status.


Assuntos
COVID-19/terapia , Imunoglobulinas Intravenosas/uso terapêutico , Administração Intravenosa , Adulto , Idoso , Biomarcadores/sangue , COVID-19/sangue , COVID-19/imunologia , COVID-19/virologia , Quimiocinas/sangue , Citocinas/sangue , Feminino , Humanos , Imunidade/imunologia , Imunoglobulinas/imunologia , Imunoglobulinas/uso terapêutico , Imunoglobulinas Intravenosas/imunologia , Inflamação/sangue , Inflamação/terapia , Inflamação/virologia , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/isolamento & purificação
19.
Anticancer Res ; 41(8): 3875-3884, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34281849

RESUMO

BACKGROUND/AIM: An excessive postoperative inflammatory response is correlated with the development of pneumonia and an unfavourable prognosis in patients undergoing esophagectomy for esophageal cancer. We assessed the influence of OSK-0028, a synthetic human ghrelin on inflammatory response and energy metabolism, on the postoperative course of patients following radical esophagectomy. PATIENTS AND METHODS: Esophageal cancer patients were randomly assigned to low-dose (LD; 0.25 µg/kg/h) or high-dose (HD; 0.5 µg/kg/h) intravenous OSK-0028 or placebo for 7 days after esophagectomy. The primary endpoint was serum interleukin-6 level on postoperative day (POD) 3. RESULTS: A total of 75 patients were enrolled (23 LD, 26 HD, 26 placebo). The median interleukin-6 levels on POD 3 were 40.95, 35.85, and 64.50 pg/ml in the placebo, LD, and HD groups, respectively, with no significant differences (p=0.78). Postoperative complications did not differ between groups. Bodyweight loss was significantly lower in patients receiving OSK-0028 than in those receiving placebo (-0.17% vs. 1.78%, p=0.043). CONCLUSION: Although OSK-0028 did not attenuate inflammatory response after esophagectomy, it prevented postoperative bodyweight loss.


Assuntos
Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/cirurgia , Esofagectomia , Grelina/uso terapêutico , Administração Intravenosa , Adulto , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Neoplasias Esofágicas/sangue , Feminino , Grelina/efeitos adversos , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Período Perioperatório , Resultado do Tratamento , Perda de Peso/efeitos dos fármacos
20.
Biomed Pharmacother ; 139: 111710, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34243616

RESUMO

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.


Assuntos
Acetaminofen/administração & dosagem , Acetaminofen/efeitos adversos , Ibuprofeno/administração & dosagem , Ibuprofeno/efeitos adversos , Dor Pós-Operatória/tratamento farmacológico , Dor Aguda/tratamento farmacológico , Administração Intravenosa/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgésicos não Narcóticos/administração & dosagem , Analgésicos não Narcóticos/efeitos adversos , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Manejo da Dor/métodos , Medição da Dor/métodos , Adulto Jovem
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