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1.
Orv Hetil ; 162(36): 1459-1465, 2021 Sep 05.
Artigo em Húngaro | MEDLINE | ID: mdl-34486529

RESUMO

Introduction: Overactive bladder syndrome is an endemic phenomenon, which has a significant impact on the quality of life. In cases where conservative treatment fails, intradetrusor onabotulinumtoxinA injection can be used as second-line therapy. Objective: To assess the safety and efficacy of onabotulinumtoxinA treatment in the management of non-neurogenic detrusor overactivity among our patients. Also, to examine the influence of perioperative factors on the effects of the efficacy. Method: We have retrospectively collected the perioperative data of 33 patients treated with intradetrusor BOTOX®. The assessment of the efficacy and complications was done by the examination of patient files and questionnaires. The results obtained during the statistical analysis were considered significant for p<0.05. Results: We have not experienced notable complications after the procedures. Only 6 patients had residual urine (p = 0.024), none of them needed to be catheterized. We have observed significant decrease in the incidence of frequency, nocturia, urgency and incontinence, just as in the number of pads needed daily (p<0.01). Quality of life and general health were significantly improved (p<0.001). We have not found any significant connection between preoperative factors and efficacy (72.7%). Discussion: Our results considering the relief of symptoms are well in line with international data. The fact that our rate of complications is - in international comparison - outstanding can be explained by a more careful patient selection and thorough preoperative assessment. Conclusion: OnabotulinumtoxinA therapy is a safe and effective solution of therapy-refractory overactive bladder. We could not identify any perioperative factor to predict postoperative efficacy of therapy. Orv Hetil. 2021; 162(36): 1459-1465.


Assuntos
Toxinas Botulínicas Tipo A , Bexiga Urinária Hiperativa , Toxinas Botulínicas Tipo A/uso terapêutico , Humanos , Injeções Intramusculares , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento , Bexiga Urinária Hiperativa/tratamento farmacológico
2.
BMC Pediatr ; 21(Suppl 1): 350, 2021 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-34496783

RESUMO

We looked at existing recommendations and supporting evidence on the effectiveness of vitamin K given after birth in preventing the haemorrhagic disease of the newborn (HDN).We conducted a literature search up to the 10th of December 2019 by using key terms and manual search in selected sources. We summarized the recommendations and the strength of the recommendation when and as reported by the authors. We summarized the main findings of systematic reviews with the certainty of the evidence as reported.All newborns should receive vitamin K prophylaxis, as it has been proven that oral and intramuscular prophylactic vitamin K given after birth are effective for preventing classical HDN. There are no randomized trials looking at the efficacy of vitamin K supplement on late HDN. There are no randomized trials comparing the oral and intramuscular route of administration of prophylactic vitamin K in newborns. From older trials and surveillance data, it seems that there is no significant difference between the intramuscular and the oral regimens for preventing classical and late HDN, provided that the oral regimen is duly completed. Evidence assessing vitamin K prophylaxis in preterm infants is scarce.


Assuntos
Sangramento por Deficiência de Vitamina K , Vitamina K , Administração Oral , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Injeções Intramusculares , Revisões Sistemáticas como Assunto , Vitamina K/uso terapêutico , Sangramento por Deficiência de Vitamina K/tratamento farmacológico , Sangramento por Deficiência de Vitamina K/prevenção & controle
3.
An Acad Bras Cienc ; 93(3): e20201924, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34406287

RESUMO

This study aimed to investigate the effects of the combined injectable contraceptive (CIC) containing estradiol valerate (EV) and norethisterone enanthate (NET-EN) on aorta function and morphology, as well as on redox status, of female Wistar rats. Female rats (9-10 weeks of age) received intramuscular injections of CIC (0.1 mg EV plus 1 mg NET-EN) or castor oil (control group, CTL) for 8 weeks, once a week. Food intake, body weight and systolic blood pressure were measured during the treatment period. Thoracic aortic segments were prepared for isometric tension recording and morphological analysis. Redox status was evaluated by total oxidant status (TOS) and lipid peroxidation (LP) on plasma and reduced glutathione (GSH) on whole blood. CIC group presented lower food intake and lower total weight gain compared to CTL group. There was no change in systolic blood pressure, vascular response of aorta to phenylephrine and acetylcholine and aorta thickness. Plasma TOS and LP values were reduced in CIC group, although GSH was not altered. It was shown that the long-term treatment with the CIC containing EV plus NET-EN does not induce endothelial dysfunction and histomorphometric changes of vascular wall, as well as improves redox status on female Wistar rats.


Assuntos
Anticoncepcionais Femininos , Animais , Estradiol , Feminino , Humanos , Injeções Intramusculares , Oxirredução , Ratos , Ratos Wistar
4.
Toxicon ; 200: 189-197, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34384786

RESUMO

The intramuscular injection of botulinum toxin is one of the most efficient ways to treat localized spasticity in patients suffering from Central Nervous System lesions like stroke, cerebral palsy and multiple sclerosis. The gait analysis based on kinetics and kinematics is a recognized way of measurement of the effect of intramuscular injection of botulinum toxin in spastic patients suffering from chronic stroke. The aim of this study is to provide evidence of the beneficial effect of botulinum toxin on characteristics of gait pattern on patients suffering from chronic stroke. So, thirteen patients with spasticity due to chronic stroke were included in the protocol and were treated by botulinum toxin injections in the lower extremity. All patients were evaluated before the injection as well as one month after the botulinum injection on a foot pressure sensitive walkway with a power plate and by the readings of seven inertial measurements units which recorded spatio-temporal specific parameters during walking, and the spasticity was measured according to modified Ashworth Scale. While all spatio-temporal parameters of motion analysis and balance improved for most of the patients after botulinum toxin injection, only one parameter, the normal to hemiplegic step length, reached statistical significant improvement (p < 0.03). Moreover the modified Ashworth score was statistically improved post injection (p < 0.001). In conclusion the use of botulinum toxin injections is beneficial in post stroke patients as this is depicted in gait parameters improvement which accompanies the spasticity reduction.


Assuntos
Toxinas Botulínicas Tipo A , Fármacos Neuromusculares , Acidente Vascular Cerebral , Toxinas Botulínicas Tipo A/uso terapêutico , Marcha , Humanos , Injeções Intramusculares , Espasticidade Muscular/tratamento farmacológico , Espasticidade Muscular/etiologia , Fármacos Neuromusculares/uso terapêutico , Estudos Prospectivos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/tratamento farmacológico , Resultado do Tratamento
6.
N Engl J Med ; 385(7): 595-608, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34379922

RESUMO

BACKGROUND: Safe and effective long-acting injectable agents for preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection are needed to increase the options for preventing HIV infection. METHODS: We conducted a randomized, double-blind, double-dummy, noninferiority trial to compare long-acting injectable cabotegravir (CAB-LA, an integrase strand-transfer inhibitor [INSTI]) at a dose of 600 mg, given intramuscularly every 8 weeks, with daily oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) for the prevention of HIV infection in at-risk cisgender men who have sex with men (MSM) and in at-risk transgender women who have sex with men. Participants were randomly assigned (1:1) to receive one of the two regimens and were followed for 153 weeks. HIV testing and safety evaluations were performed. The primary end point was incident HIV infection. RESULTS: The intention-to-treat population included 4566 participants who underwent randomization; 570 (12.5%) identified as transgender women, and the median age was 26 years (interquartile range, 22 to 32). The trial was stopped early for efficacy on review of the results of the first preplanned interim end-point analysis. Among 1698 participants from the United States, 845 (49.8%) identified as Black. Incident HIV infection occurred in 52 participants: 13 in the cabotegravir group (incidence, 0.41 per 100 person-years) and 39 in the TDF-FTC group (incidence, 1.22 per 100 person-years) (hazard ratio, 0.34; 95% confidence interval, 0.18 to 0.62). The effect was consistent across prespecified subgroups. Injection-site reactions were reported in 81.4% of the participants in the cabotegravir group and in 31.3% of those in the TDF-FTC group. In the participants in whom HIV infection was diagnosed after exposure to CAB-LA, INSTI resistance and delays in the detection of HIV infection were noted. No safety concerns were identified. CONCLUSIONS: CAB-LA was superior to daily oral TDF-FTC in preventing HIV infection among MSM and transgender women. Strategies are needed to prevent INSTI resistance in cases of CAB-LA PrEP failure. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 083 ClinicalTrials.gov number, NCT02720094.).


Assuntos
Infecções por HIV/prevenção & controle , Inibidores de Integrase de HIV/administração & dosagem , Profilaxia Pré-Exposição , Piridonas/administração & dosagem , Tenofovir/uso terapêutico , Administração Oral , Adulto , Idoso , Fármacos Anti-HIV/uso terapêutico , Preparações de Ação Retardada/administração & dosagem , Método Duplo-Cego , Esquema de Medicação , Resistência a Medicamentos/genética , Feminino , Inibidores de Integrase de HIV/efeitos adversos , Homossexualidade Masculina , Humanos , Injeções Intramusculares/efeitos adversos , Análise de Intenção de Tratamento , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Piridonas/efeitos adversos , Pessoas Transgênero , Adulto Jovem
7.
Molecules ; 26(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34361749

RESUMO

Cefquinome and ceftiofur are ß-lactam antibiotics used for the treatment of bacterial infections in swine. Although these antimicrobials are administered intramuscularly, the exposure of the gut microbiota to these cephalosporins is not well described. This exposure can contribute to the emergence and spread of antimicrobials in the environment and to the possible spread of antimicrobial resistance genes. To assess the impact of drug administration on the intestinal excretion of these antimicrobials it is essential to measure the amounts of native compound and metabolites in feces. Two (ultra)-high-performance liquid chromatography-tandem mass spectrometry ((U)HPLC-MS/MS) methods were developed and validated, one for the determination of cefquinome and ceftiofur and the other for the determination of ceftiofur residues, measured as desfuroylceftiofuracetamide, in porcine feces. The matrix-based calibration curve was linear from 5 ng g-1 to 1000 ng g-1 for cefquinome (correlation coefficient (r) = 0.9990 ± 0.0007; goodness of fit (gof) = 3.70 ± 1.43) and ceftiofur (r = 0.9979 ± 0.0009; gof = 5.51 ± 1.14) and quadratic from 30 ng g-1 to 2000 ng g-1 for desfuroylceftiofuracetamide (r = 0.9960 ± 0.0020; gof = 7.31 ± 1.76). The within-day and between-day precision and accuracy fell within the specified ranges. Since ß-lactam antibiotics are known to be unstable in feces, additional experiments were conducted to adjust the sampling protocol in order to minimize the impact of the matrix constituents on the stability of the analytes. Immediately after sampling, 500 µL of an 8 µg mL-1 tazobactam solution in water was added to 0.5 g feces, to reduce the degradation in matrix.


Assuntos
Acetamidas/isolamento & purificação , Antibacterianos/isolamento & purificação , Cefalosporinas/isolamento & purificação , Cromatografia Líquida de Alta Pressão/normas , Furanos/isolamento & purificação , Espectrometria de Massas em Tandem/normas , Acetamidas/administração & dosagem , Animais , Antibacterianos/administração & dosagem , Calibragem , Cefalosporinas/administração & dosagem , Cromatografia Líquida de Alta Pressão/métodos , Fezes/química , Feminino , Furanos/administração & dosagem , Injeções Intramusculares , Masculino , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Suínos , Espectrometria de Massas em Tandem/métodos , Tazobactam/química
8.
Rev Bras Enferm ; 75(1): e20201119, 2021.
Artigo em Inglês, Português | MEDLINE | ID: mdl-34431926

RESUMO

OBJECTIVES: to compare adverse events after administrating hepatitis A vaccine intramuscularly in the ventro-gluteal region between techniques with and without aspiration. METHODS: randomized double-blind clinical trial, using hepatitis A vaccine (inactivated) in the ventro-gluteal region, with a sample of 74 participants in the intervention group, vaccinated with the slow injection technique without aspiration, and 74 participants in the control group undergoing slow injection with aspiration. Daily assessment of participants was carried out in the 72 hours after vaccination, in order to ascertain local, systemic adverse events, local and contralateral temperatures. RESULTS: the occurrence of local and systemic adverse events was homogeneous between the groups in the three days after vaccination (p>0.05). There was no influence of sex, race, pre-existing disease and use of medication. CONCLUSIONS: the intramuscular vaccination technique without aspiration in the ventro-gluteal region is safe for adverse events following immunization compared to the conventional technique with aspiration.


Assuntos
Imunização , Vacinação , Nádegas , Método Duplo-Cego , Humanos , Injeções Intramusculares
9.
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
10.
Turk J Pediatr ; 63(3): 372-383, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34254482

RESUMO

BACKGROUND: Inadequate practices in diagnosis and management of anaphylaxis in parallel with an increase in its prevalence may cause serious public health problems today. This is the first study aiming to assess the theoretical knowledge of professional and non-professional healthcare workers from different lines of the healthcare service chain about anaphylaxis management, and their practice approaches for epinephrine autoinjectors (EAIs) together. METHODS: The study included 697 participants comprising physicians, dentists, pharmacists, and school staff. In face-to-face interviews, each participant was asked to fill out the questionnaire forms prepared for assessing their demographic characteristics, experience with a case of anaphylaxis and EAI and theoretical knowledge about the diagnosis and treatment of anaphylaxis, and to demonstrate how to use EAI in practice with trainer device. RESULTS: The rates of 391 physicians, 98 dentists, 102 pharmacists and 105 school staff of knowing the diagnosis criteria of anaphylaxis were 47.6%, 31.6%, 31.1%, 19%, and knowing the first and life-saving treatment of anaphylaxis were 87.2%, 79.6%, 47.6%, 15.2%, respectively. Predictors that affected physicians in knowing the first and life-saving treatment of anaphylaxis were having experience with EAIs [OR:5.5, (%95CI:1.330-23.351, p=0.015)] and a case of anaphylaxis [OR:2.4, (%95CI:1.442-4.020, p=0.001)], and knowing the administration route of epinephrine correctly [OR:1.9, (%95CI:1.191-3.314, p=0.008)]. 31.1% of the participants demonstrated the EAI usage correctly. The EAI usage steps with the most errors were `Place the appropriate injection tip into outer thigh/Press the trigger so it `clicks`` and `Turn the trigger to arrow direction` (60.3% and 34.9%, respectively). CONCLUSIONS: Healthcare workers` knowledge level regarding anaphylaxis management and ability to use EAIs correctly are not adequate. That most errors were made in the same steps of EAI usage indicates that the industry should continue to strive for developing the ideal life-saving device.


Assuntos
Anafilaxia , Anafilaxia/diagnóstico , Anafilaxia/tratamento farmacológico , Anafilaxia/epidemiologia , Epinefrina , Pessoal de Saúde , Humanos , Injeções Intramusculares , Instituições Acadêmicas , Inquéritos e Questionários
11.
CNS Drugs ; 35(7): 743-767, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34228301

RESUMO

Recombinant interferon (IFN) ß-1b was approved by the US Food and Drug Administration as the first disease-modifying therapy (DMT) for multiple sclerosis (MS) in 1993. Since that time, clinical trials and real-world observational studies have demonstrated the effectiveness of IFN therapies. The pivotal intramuscular IFN ß-1a phase III trial published in 1996 was the first to demonstrate that a DMT could reduce accumulation of sustained disability in MS. Patient adherence to treatment is higher with intramuscular IFN ß-1a, given once weekly, than with subcutaneous formulations requiring multiple injections per week. Moreover, subcutaneous IFN ß-1a is associated with an increased incidence of injection-site reactions and neutralizing antibodies compared with intramuscular administration. In recent years, revisions to MS diagnostic criteria have improved clinicians' ability to identify patients with MS and have promoted the use of magnetic resonance imaging (MRI) for diagnosis and disease monitoring. MRI studies show that treatment with IFN ß-1a, relative to placebo, reduces T2 and gadolinium-enhancing lesions and gray matter atrophy. Since the approval of intramuscular IFN ß-1a, a number of high-efficacy therapies have been approved for MS, though the benefit of these high-efficacy therapies should be balanced against the increased risk of serious adverse events associated with their long-term use. For some subpopulations of patients, including pregnant women, the safety profile of IFN ß formulations may provide a particular benefit. In addition, the antiviral properties of IFNs may indicate potential therapeutic opportunities for IFN ß in reducing the risk of viral infections such as COVID-19.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Interferon beta-1a/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Humanos , Injeções Intramusculares , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/fisiopatologia , SARS-CoV-2 , Resultado do Tratamento
12.
J Infect ; 83(3): 354-360, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34298035

RESUMO

BACKGROUND: The effect of the Toll-like receptor 7 agonist imiquimod before intradermal (ID) or intramuscular (IM) influenza vaccine in immunocompromised hosts is unknown. METHODS: In this open-label randomized controlled trial, kidney transplant recipients (KT) and people living with HIV (PLWH) were randomized to receive IM trivalent inactivated influenza vaccine alone (IM), IM vaccine after topical imiquimod (imi+IM) or ID vaccine after topical imiquimod (imi+ID). Immunogenicity was assessed by hemagglutination inhibition assay. The primary outcome was vaccine response, defined as seroconversion to at least one viral strain at day 21. RESULTS: Seventy patients (35 KT and 35 PLWH) received IM (24), imi+IM (22), or imi+ID (24) vaccine. Vaccine response was 61% (14/23) with IM, 59% (13/22) with imi+IM, and 65% (15/23) with imi+ID vaccine (P = 0.909). Vaccine response was associated with HIV infection compared to kidney transplantation (adjusted-OR 3.74, 95% CI 1.25 - 11.23, P = 0.019), but not with imiquimod application nor ID injection. After vaccination, seroprotection to all viral strains was 79% (19/24) with IM, 68% (15/22) with imi+IM, and 70% (16/23) with imi+ID (P = 0.657). We did not observe any vaccine-related severe adverse event. CONCLUSIONS: In our study, topical imiquimod did not improve the immunogenicity of influenza vaccine in KT and in PLWH.


Assuntos
Infecções por HIV , Vacinas contra Influenza , Influenza Humana , Anticorpos Antivirais , Infecções por HIV/complicações , Testes de Inibição da Hemaglutinação , Humanos , Imiquimode , Hospedeiro Imunocomprometido , Influenza Humana/prevenção & controle , Injeções Intramusculares , Estações do Ano , Vacinas de Produtos Inativados
13.
Vaccine ; 39(37): 5326-5330, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34275671

RESUMO

BACKGROUND: Recent phase-3 clinical trials have demonstrated very encouraging results for mRNA based vaccines against COVID-19. Current FDA and manufacturer guidelines mandate intramuscular administration of these vaccines, as other administration routes may not provide the same levels of effectiveness and safety. Observing the vast amount of published media images of persons receiving their vaccines, the authors noted in many cases the injection technique involved skin bunching, raising concerns of inadequate deltoid muscle penetration and consequent lowered vaccine efficacy. Our study hypothesis was that skin bunching will increase the skin-to-muscle distance over 20 mm, the maximal distance allowing the required 5 mm muscle penetration with a 25 mm needle. MATERIALS AND METHODS: 60 adult volunteers from our hospital staff were recruited, and using ultrasound, the skin-to-muscle distance measured in three positions: flat, skin bunching and muscle bunching. The skin-to-muscle distance difference and correlation with gender and BMI were calculated. RESULTS: Skin bunching significantly increased the skin-to-muscle distance in all subjects. In 6 (10%) subjects, this increase exceeded the 20 mm limit. Having a skin-to-deltoid distance of 20 mm or more strongly correlated with a BMI of 30 or more. CONCLUSIONS: Skin bunching will prevent adequate intramuscular injection of vaccines in a small percentage of persons, but as hundreds of millions are expected to receive mRNA vaccines in the coming months, the multiplied result can have significant personal and societal consequences for millions of people globally, especially in obese populations, and therefore this practice should be strictly discouraged.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Vacinas Sintéticas , Adulto , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/efeitos adversos , Músculo Deltoide , Humanos , Injeções Intramusculares , RNA Mensageiro , SARS-CoV-2 , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/efeitos adversos
14.
Emerg Microbes Infect ; 10(1): 1574-1588, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34289779

RESUMO

A safe and effective vaccine is urgently needed to control the unprecedented COVID-19 pandemic. Four adenovirus-vectored vaccines expressing spike (S) protein have been approved for use. Here, we generated several recombinant chimpanzee adenovirus (AdC7) vaccines expressing S, receptor-binding domain (RBD), or tandem-repeat dimeric RBD (RBD-tr2). We found vaccination via either intramuscular or intranasal route was highly immunogenic in mice to elicit both humoral and cellular immune responses. AdC7-RBD-tr2 showed higher antibody responses compared to either AdC7-S or AdC7-RBD. Intranasal administration of AdC7-RBD-tr2 additionally induced mucosal immunity with neutralizing activity in bronchoalveolar lavage fluid. Either single-dose or two-dose mucosal administration of AdC7-RBD-tr2 protected mice against SARS-CoV-2 challenge, with undetectable subgenomic RNA in lung and relieved lung injury. AdC7-RBD-tr2-elicted sera preserved the neutralizing activity against the circulating variants, especially the Delta variant. These results support AdC7-RBD-tr2 as a promising COVID-19 vaccine candidate.


Assuntos
Adenoviridae/genética , Anticorpos Antivirais/sangue , Vacinas contra COVID-19/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Administração Intranasal , Animais , Anticorpos Neutralizantes/sangue , COVID-19 , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/genética , Chlorocebus aethiops , Feminino , Vetores Genéticos/genética , Células HEK293 , Humanos , Imunogenicidade da Vacina , Injeções Intramusculares , Camundongos , Camundongos Endogâmicos BALB C , Pan troglodytes/virologia , Ligação Proteica , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/administração & dosagem , Glicoproteína da Espícula de Coronavírus/genética , Vacinação , Células Vero
15.
Artigo em Russo | MEDLINE | ID: mdl-34283541

RESUMO

Spasticity in patients with cerebral palsy (CP) is the main impediment to normal locomotion. The function of the Central Pattern Generator (CPG), i.e. a group of neural chains in the spinal cord, stands at the core of any rhythmical movement. CPG can generate locomotion patterns without supraspinal control, which can have both positive and negative impact on the ability to move. Performing the motor tasks such as walking, running and swimming, creates the consistent rhythmical movement of legs and arms through interaction between CPGs of upper and lower extremities. This interaction can cause the activation of pathological movement patterns in lower extremities in response to upper limb spasticity. Thus, neural chains in the spinal cord become the generator of pathologically increased excitation which has developed as a result of a focal lesion in the CNS. All the statements described above show the importance of introducing the upper limb injections of bFotulinum toxin A in the protocol in order to develop normal locomotion. The PUL study approved the optimal level of efficacy and favourable safety profile of botulinum toxin A in children with CP and upper limb muscle spasticity.


Assuntos
Toxinas Botulínicas Tipo A , Paralisia Cerebral , Clostridium botulinum , Fármacos Neuromusculares , Toxinas Botulínicas Tipo A/uso terapêutico , Paralisia Cerebral/complicações , Paralisia Cerebral/tratamento farmacológico , Criança , Humanos , Injeções Intramusculares , Espasticidade Muscular/tratamento farmacológico , Espasticidade Muscular/etiologia , Fármacos Neuromusculares/uso terapêutico
16.
Methods Mol Biol ; 2320: 285-293, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34302665

RESUMO

Myocardial infarction is caused by a lack of oxygen due to blockage of a coronary artery and is a common cause of heart failure. Despite therapeutic advances, the prognosis of patients with heart failure is poor. One of the reasons is that present therapeutic approaches do not restore the loss of cardiac tissue. Stem cell-based therapies have the potential to regenerate the myocardium, and numerous studies using stem cells have shown improved cardiac function and reduced infarct size. In this chapter, we describe our methodology for transplanting human induced pluripotent stem cell-derived cardiomyocytes into immunodeficient mouse hearts with myocardial infarction.


Assuntos
Células-Tronco Pluripotentes Induzidas/citologia , Miócitos Cardíacos/transplante , Animais , Modelos Animais de Doenças , Coração/fisiologia , Humanos , Injeções Intramusculares , Ligadura , Masculino , Camundongos , Camundongos Endogâmicos NOD , Infarto do Miocárdio/terapia , Regeneração , Respiração Artificial/métodos , Respiração Artificial/veterinária , Toracotomia/métodos , Toracotomia/veterinária
17.
Nat Commun ; 12(1): 4636, 2021 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-34330906

RESUMO

Chikungunya virus (CHIKV) is a reemerging mosquito-borne virus that causes swift outbreaks. Major concerns are the persistent and disabling polyarthralgia in infected individuals. Here we present the results from a first-in-human trial of the candidate simian adenovirus vectored vaccine ChAdOx1 Chik, expressing the CHIKV full-length structural polyprotein (Capsid, E3, E2, 6k and E1). 24 adult healthy volunteers aged 18-50 years, were recruited in a dose escalation, open-label, nonrandomized and uncontrolled phase 1 trial (registry NCT03590392). Participants received a single intramuscular injection of ChAdOx1 Chik at one of the three preestablished dosages and were followed-up for 6 months. The primary objective was to assess safety and tolerability of ChAdOx1 Chik. The secondary objective was to assess the humoral and cellular immunogenicity. ChAdOx1 Chik was safe at all doses tested with no serious adverse reactions reported. The vast majority of solicited adverse events were mild or moderate, and self-limiting in nature. A single dose induced IgG and T-cell responses against the CHIKV structural antigens. Broadly neutralizing antibodies against the four CHIKV lineages were found in all participants and as early as 2 weeks after vaccination. In summary, ChAdOx1 Chik showed excellent safety, tolerability and 100% PRNT50 seroconversion after a single dose.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Febre de Chikungunya/imunologia , Vírus Chikungunya/imunologia , Vacinas Virais/imunologia , Adolescente , Adulto , Febre de Chikungunya/prevenção & controle , Febre de Chikungunya/virologia , Vírus Chikungunya/classificação , Vírus Chikungunya/fisiologia , Citocinas/imunologia , Citocinas/metabolismo , Ensaio de Imunoadsorção Enzimática , Fadiga/induzido quimicamente , Feminino , Cefaleia/induzido quimicamente , Humanos , Imunoglobulina G/imunologia , Injeções Intramusculares , Masculino , Pessoa de Meia-Idade , Linfócitos T/imunologia , Linfócitos T/metabolismo , Vacinação/métodos , Vacinas Virais/administração & dosagem , Vacinas Virais/efeitos adversos , Adulto Jovem
18.
Am J Psychiatry ; 178(7): 660-671, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34170188

RESUMO

OBJECTIVE: Sublingual buprenorphine-naloxone and extended-release injection naltrexone are effective treatments, with distinct mechanisms, for opioid use disorder. The authors examined whether patients' demographic and clinical characteristics were associated with better response to one medication or the other. METHODS: In a multisite 24-week randomized comparative-effectiveness trial of assignment to buprenorphine-naloxone (N=287) compared with extended-release naltrexone (N=283) comprising inpatients planning to initiate medication treatment for opioid use disorder, 50 demographic and clinical characteristics were examined as moderators of the effect of medication assignment on relapse to regular opioid use and failure to initiate medication. Moderator-by-medication interactions were estimated using logistic regression with correction for multiple testing. RESULTS: In the intent-to-treat sample, patients who reported being homeless had a lower relapse rate if they were assigned to receive extended-release naltrexone (51.6%) compared with buprenorphine-naloxone (70.4%) (odds ratio=0.45, 95% CI=0.22, 0.90); patients who were not homeless had a higher relapse rate if they were assigned to extended-release naltrexone (70.9%) compared with buprenorphine-naloxone (53.1%) (odds ratio=2.15, 95% CI=1.44, 3.21). In the subsample of patients who initiated medication, the interaction was not significant, with a similar pattern of lower relapse with extended-release naltrexone (41.4%) compared with buprenorphine (68.6%) among homeless patients (odds ratio=0.32, 95% CI=0.15, 0.68) but less difference among those not homeless (extended-release naltrexone, 57.2%; buprenorphine, 52.0%; odds ratio=1.24, 95% CI=0.80, 1.90). For failure to initiate medication, moderators were stated preference for medication (failure was less likely if the patient was assigned to the medication preferred), parole and probation status (fewer failures with extended-release naltrexone for those on parole or probation), and presence of pain and timing of randomization (more failure with extended-release naltrexone for patients endorsing moderate to severe pain and randomized early while still undergoing medically managed withdrawal). CONCLUSIONS: Among patients with opioid use disorder admitted to inpatient treatment, homelessness, parole and probation status, medication preference, and factors likely to influence tolerability of medication initiation may be important in matching patients to buprenorphine or extended-release naltrexone.


Assuntos
Combinação Buprenorfina e Naloxona/administração & dosagem , Preparações de Ação Retardada/administração & dosagem , Naltrexona/administração & dosagem , Antagonistas de Entorpecentes/administração & dosagem , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Administração Sublingual , Adulto , Combinação Buprenorfina e Naloxona/uso terapêutico , Preparações de Ação Retardada/uso terapêutico , Feminino , Humanos , Injeções Intramusculares , Masculino , Pessoa de Meia-Idade , Naltrexona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Resultado do Tratamento , Adulto Jovem
19.
N Engl J Med ; 384(22): 2115-2123, 2021 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-34077644

RESUMO

BACKGROUND: Neisseria meningitidis serogroups A, B, C, W, X, and Y cause outbreaks of meningococcal disease. Quadrivalent conjugate vaccines targeting the A, C, W, and Y serogroups are available. A pentavalent vaccine that also includes serogroup X (NmCV-5) is under development. METHODS: We conducted a phase 2, observer-blinded, randomized, controlled trial involving Malian children 12 to 16 months of age. Participants were assigned in a 2:2:1 ratio to receive nonadjuvanted NmCV-5, alum-adjuvanted NmCV-5, or the quadrivalent vaccine MenACWY-D, administered intramuscularly in two doses 12 weeks apart. Participants were followed for safety for 169 days. Immunogenicity was assessed with an assay for serum bactericidal antibody (SBA) with rabbit complement on days 0, 28, 84, and 112. RESULTS: A total of 376 participants underwent randomization, with 150 assigned to each NmCV-5 group and 76 to the MenACWY-D group; 362 participants received both doses of vaccine. A total of 1% of the participants in the nonadjuvanted NmCV-5 group, 1% of those in the adjuvanted NmCV-5 group, and 4% of those in the MenACWY-D group reported local solicited adverse events; 6%, 5%, and 7% of the participants, respectively, reported systemic solicited adverse events. An SBA titer of at least 128 was seen in 91 to 100% (for all five serotypes) of the participants in the NmCV-5 groups and in 36 to 99% (excluding serogroup X) of those in the MenACWY-D group at day 84 (before the second dose); the same threshold was met in 99 to 100% (for all five serotypes) of the participants in the NmCV-5 groups and in 92 to 100% (excluding serogroup X) of those in the MenACWY-D group at day 112. Immune responses to the nonadjuvanted and adjuvanted NmCV-5 formulations were similar. CONCLUSIONS: No safety concerns were identified with two doses of NmCV-5. A single dose of NmCV-5 elicited immune responses that were similar to those observed with two doses of MenACWY-D. Adjuvanted NmCV-5 provided no discernible benefit over nonadjuvanted NmCV-5. (Funded by the U.K. Foreign, Commonwealth, and Development Office; ClinicalTrials.gov number, NCT03295318.).


Assuntos
Imunogenicidade da Vacina , Infecções Meningocócicas/prevenção & controle , Vacinas Meningocócicas/imunologia , Adjuvantes Imunológicos , Compostos de Alúmen , Feminino , Humanos , Lactente , Injeções Intramusculares , Masculino , Mali , Vacinas Meningocócicas/efeitos adversos , Neisseria meningitidis , Sorogrupo , Método Simples-Cego , Vacinas Conjugadas/imunologia
20.
J Subst Abuse Treat ; 127: 108355, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34134881

RESUMO

BACKGROUND: Usual treatment for persons with opioid use disorders who are in prison is detoxification with referral to treatment after release but failure to engage in treatment and relapse is common. Starting medication treatment before release might improve outcomes. OBJECTIVES: Determine if administering extended-release injectable naltrexone (XR-NTX) before release (BR) from prison results in less relapse within the first three months after release than when offered by referral after release (AR). METHODS: The study randomized 1:1 persons who had an OUD, expressed interest in XR-NTX, and met study admission criteria to receive XR-NTX BR or at a local program AR, with continued medication and counseling available at that program. RESULTS: Four-hundred and two persons expressed interest in the study, 222 consented, and the study randomized 146. Uncertainty about release dates resulted in a time lag between randomization and final disposition during which 60 of the randomized patients were sentenced to other facilities, withdrew consent, or became otherwise unavailable for study treatment, leaving 86 for outcome analyses (38, BR; 48 AR). Missed follow-up appointments on the remaining 86 led to development of a phone-based questionnaire to determine presence/absence of relapse. Using it to supplement other data, we were able to confirm relapse or nonrelapse for 63 of the 86 (73%). All BR and a third of the AR patients received their first XR-NTX dose, however dropout was high and nonrelapse by month three was not significantly different between BR (39.5%) and AR (25%) (Chisq (2) = 3.23, p = 0.20). CONCLUSIONS: BR patients were much more likely to receive medication and its extended relapse and overdose protection effects in the first weeks after release. Dropout was high and the study detected no significant difference in relapse by month 3; however, the less-than-planned number of patients and missing data make this finding inconclusive.


Assuntos
Transtornos Relacionados ao Uso de Opioides , Prisioneiros , Analgésicos Opioides/uso terapêutico , Preparações de Ação Retardada/uso terapêutico , Humanos , Injeções Intramusculares , Naltrexona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Prisões
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