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1.
Int J Antimicrob Agents ; 55(3): 105875, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31926285

RESUMO

Use of peripheral venous catheters (PVCs) is very common in hospitals. According to the literature, after a visit to the emergency department >75% of hospitalised patients carry a PVC, among which almost 50% are useless. In this study, the presence and complications of PVCs in an infectious diseases (ID) unit of a French tertiary-care university hospital were monitored. A total of 614 patients were prospectively included over a 6-month period. Among the 614 patients, 509 (82.9%) arrived in the ID unit with a PVC, of which 260 (51.1%) were judged unnecessary and were removed as soon as the patients were examined by the ID team. More than one-half of PVCs were removed within 24 h in the unit (308/509; 60.5%). PVCs were complicated for 65 (12.8%) of the 509 patients, with complications including extravasation, cutaneous necrosis, lymphangitis, phlebitis, tearing off the patient, superficial venous thrombosis and arthritis. We must therefore continue to search for unjustified PVC insertion. Alternatives to the intravenous administration route must be proposed, such as subcutaneous infusion or oral antibiotic therapy.


Assuntos
Cateterismo Periférico/efeitos adversos , Infecções Relacionadas a Cateter/etiologia , Vias de Administração de Medicamentos , Serviço Hospitalar de Emergência , Humanos , Flebite/etiologia
3.
J Oncol Pharm Pract ; 26(1): 51-59, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30866715

RESUMO

BACKGROUND: Different international organizations recommend safety measures for the use of vincristine to prevent wrong route administrations. A central recommendation is to use infusion bags instead of syringes to prevent confusion with intrathecal chemotherapy. This study aimed to investigate the implementation of safety measures for vincristine and intrathecal chemotherapies in Switzerland. METHOD: We conducted a written survey among hospital pharmacies of all general care and pediatric hospitals in Switzerland (n = 102). A responsible person of each hospital pharmacy was invited by email to participate in the online survey in May 2018. RESULTS: Of 66 responding hospitals (response rate 65%), 27 have a hospital pharmacy preparing parenteral chemotherapy. All of these hospitals prepared vincristine in 2017, while 21 also prepared intrathecal chemotherapy. Of these 21, 16 hospitals prepared vincristine as syringes, with small volume syringes being the most widely distributed dosage form. A switch from syringes to infusion bags was discussed in seven hospitals, and discussions led to plans for switch in two. The most prevalent safety measures were labeling for vincristine and special delivery for intrathecal drugs. Of hospitals preparing both vincristine syringes and intrathecal chemotherapy, four reported to have no safety measures implemented neither for vincristine nor for intrathecal chemotherapy. CONCLUSION: International recommendations are not widely implemented in Swiss hospitals. Syringes are still in use and other safety measures are sparsely disseminated. Thus, Swiss vincristine patients are still at an increased risk for wrong route application. Recommendations have to be further disseminated and implementation could be enhanced.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Erros de Medicação/prevenção & controle , Serviço de Farmácia Hospitalar/normas , Inquéritos e Questionários , Vincristina/administração & dosagem , Antineoplásicos Fitogênicos/efeitos adversos , Vias de Administração de Medicamentos , Feminino , Humanos , Masculino , Serviço de Farmácia Hospitalar/métodos , Suíça/epidemiologia , Seringas/normas , Vincristina/efeitos adversos
4.
J Dairy Sci ; 103(1): 972-991, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31704022

RESUMO

The objective of this study was to test the effects of essential fatty acids (EFA), particularly α-linolenic acid, and conjugated linoleic acid (CLA) supplementation on fatty acid (FA) composition, performance, and systemic and hepatic antioxidative and inflammatory responses in dairy cows. Four cows (126 ± 4 d in milk) were investigated in a 4 × 4 Latin square and were abomasally infused with 1 of the following for 6 wk: (1) coconut oil (control treatment, CTRL; 38.3 g/d; providing saturated FA), (2) linseed and safflower oil (EFA treatment; 39.1 and 1.6 g/d, respectively; providing mainly α-linolenic acid), (3) Lutalin (BASF, Ludwigshafen, Germany; CLA treatment; cis-9,trans-11 and trans-10,cis-12 CLA, 4.6 g/d each), (4) or EFA+CLA. The initial dosage was doubled every 2 wk, resulting in 3 dosages (dosage 1, 2, and 3). Cows were fed a corn silage-based total mixed ration with a high n-6/n-3 FA ratio. Dry matter intake and milk yield were recorded daily, and milk composition was measured weekly. The FA compositions of milk fat and blood plasma were analyzed at wk 0, 2, 4, and 6. The plasma concentration and hepatic mRNA abundance of parameters linked to the antioxidative and inflammatory response were analyzed at wk 0 and 6 of each treatment period. Infused FA increased in blood plasma and milk of the respective treatment groups in a dose-dependent manner. The n-6/n-3 FA ratio in milk fat was higher in CTRL and CLA than in EFA and EFA+CLA. The sum of FA

Assuntos
Antioxidantes/metabolismo , Bovinos , Ácidos Graxos/administração & dosagem , Inflamação/veterinária , Ácidos Linoleicos Conjugados/administração & dosagem , Abomaso/metabolismo , Animais , Dieta/veterinária , Suplementos Nutricionais , Vias de Administração de Medicamentos , Metabolismo Energético , Ácidos Graxos/metabolismo , Feminino , Inflamação/prevenção & controle , Injeções , Lactação/fisiologia , Ácidos Linoleicos Conjugados/farmacologia , Leite/metabolismo
5.
Am J Surg ; 219(1): 58-64, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30982572

RESUMO

BACKGROUND: Peritoneal cancer index (PCI) is an important prognostic factor in colorectal cancer peritoneal metastases (CRPM), however it fails to consider the time period over which disease burden develops. The volume-time index (VTI) is the ratio between PCI and time from primary tumour resection. METHODS: A retrospective cohort study of 182 patients managed from 1996 to 2017 was performed. RESULTS: As stratified by high vs low VTI groups, median overall survival (OS) was 23 months (95% 17-46) vs 44 months (95% 35-72) with a difference in 5-year OS of 20.3% (95%CI 10.2-40.4) vs 40.1% (95%CI 29.7-54.1), p = 0.002. No difference in 5-year recurrence free survival (RFS) exists. On multivariable analysis, an elevated VTI was independently associated with poorer OS (adjusted HR 3.20, 95%CI 1.64-6.23, p < 0.001) and RFS (adjusted HR 1.90, 95%CI 1.10-3.29, p = 0.02). CONCLUSION: VTI is an independent prognostic factor for OS and RFs in patients with CRPM undergoing CRS/IPC, behaving as a surrogate of tumour aggressiveness.


Assuntos
Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/patologia , Adulto , Idoso , Antineoplásicos/administração & dosagem , Estudos de Coortes , Neoplasias Colorretais/terapia , Procedimentos Cirúrgicos de Citorredução , Vias de Administração de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/terapia , Peritônio , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Carga Tumoral
6.
Pharm Res ; 37(1): 12, 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31873819

RESUMO

Intraperitoneal (IP) route of drug administration in laboratory animals is a common practice in many in vivo studies of disease models. While this route is an easy to master, quick, suitable for chronic treatments and with low impact of stress on laboratory rodents, there is a common concern that it may not be an acceptable route for drug administration in experimental studies. The latter is likely due to sparsity of information regarding pharmacokinetics of pharmacological agents and the mechanisms through which agents get systemic exposure after IP administration. In this review, we summarize the main mechanisms involved in bioavailability of IP administered drugs and provide examples of pharmacokinetic profiles for small and large molecules in comparison to other routes of administration. We conclude with a notion that IP administration of drugs in experimental studies involving rodents is a justifiable route for pharmacological and proof-of-concept studies where the goal is to evaluate the effect(s) of target engagement rather than properties of a drug formulation and/or its pharmacokinetics for clinical translation.


Assuntos
Composição de Medicamentos/métodos , Injeções Intraperitoneais/métodos , Preparações Farmacêuticas/química , Animais , Disponibilidade Biológica , Vias de Administração de Medicamentos , Humanos , Injeções Subcutâneas/métodos , Modelos Animais , Tamanho da Partícula , Farmacocinética , Transdução de Sinais
7.
Int J Mol Sci ; 21(1)2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31861465

RESUMO

The incidence of brain metastases has increased in the last 10 years. However, the survival of patients with brain metastases remains poor and challenging in daily practice in medical oncology. One of the mechanisms suggested for the persistence of a high incidence of brain metastases is the failure to cross the blood-brain barrier of most chemotherapeutic agents, including the more recent targeted therapies. Therefore, new pharmacological approaches are needed to optimize the efficacy of anticancer drug protocols. In this article, we present recent findings in molecular data on brain metastases. We then discuss published data from pharmacological studies on the crossing of the blood-brain barrier by anticancer agents. We go on to discuss future developments to facilitate drug penetration across the blood-brain barrier for the treatment of brain metastases among cancer patients, using physical methods or physiological transporters.


Assuntos
Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/secundário , Animais , Antineoplásicos/administração & dosagem , Biomarcadores , Neoplasias Encefálicas/diagnóstico , Permeabilidade da Membrana Celular , Vias de Administração de Medicamentos , Sistemas de Liberação de Medicamentos , Desenvolvimento de Medicamentos , Humanos , Terapia de Alvo Molecular
8.
BMC Vet Res ; 15(1): 362, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31651323

RESUMO

BACKGROUND: Tembusu virus (TMUV) usually affects adult ducks, causing a severe drop of egg production. It has also been shown to be pathogenic in commercial Pekin ducklings below 7 weeks of age. Here, we report a TMUV-caused neurological disease in young egg-type ducklings and the pathogenicity of the egg-type duck-origin TMUV isolates in meat-type Pekin ducklings. RESULTS: The disease occurred in 25 to 40-day-old Jinding ducklings in China, and was characterized by paralysis. Gross lesions were lacking and microscopic lesions appeared chiefly in brain and spleen. Inoculation in embryonated duck eggs resulted in isolation of TMUV Y and GL. The clinical signs and microscopic lesions observed in the spontaneously infected egg-type ducks were repeated in Pekin ducklings by experimental infection. Notably, both Y and GL strains caused 100% mortality in the case of 2-day-old inoculation by intracerebral route. High mortalities (80 and 70%) also occurred following infection of the Y virus at 2 days of age by intramuscular route and at 9 days of age by intracerebral route. CONCLUSIONS: These findings demonstrate that the egg-type duck-origin TMUVs exhibit high pathogenicity in Pekin ducklings, and that the severity of the disease in ducklings is dependent on the infection route and the age of birds at the time of infection. The availability of the highly pathogenic TMUV strains provides a useful material with which to begin investigations into the molecular basis of TMUV pathogenicity in ducks.


Assuntos
Infecções por Flavivirus/veterinária , Flavivirus/patogenicidade , Doenças das Aves Domésticas/virologia , Fatores Etários , Animais , Linhagem Celular , Cricetinae , Vias de Administração de Medicamentos/veterinária , Patos/virologia , Flavivirus/genética , Infecções por Flavivirus/patologia , Infecções por Flavivirus/virologia , Paralisia/veterinária , Paralisia/virologia , Doenças das Aves Domésticas/patologia
9.
Chin J Nat Med ; 17(9): 690-697, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31526504

RESUMO

Herein, the purpose of this study is to evaluate the effects of kaempferol on bioavailability and pharmacokinetics of nifedipine and its metabolite dehydronifedipine in rats. The experimental design is based on with or without kaempferol in the oral and intravenous administration of nifedipine in rats. Moreover, the pharmacokinetic parameters including nifedipine and dehydronifedipine were evaluated in rats.The in vitro studies ofkaempferol were investigated on P-glycoprotein (P-gp) and cytochrome P450 (CYP) 3A4 activity. Kaempferol reduced a 50% inhibitory concentration (IC50) of 8.6 µmol·L-1 on CYP3A4 enzyme activity. Moreover, kaempferol clearly improved the cell internalization of rhodamine-123 in MCF-7/ADR cells overexpressing P-gp. Depending on increased concentrations of kaempferol, the areas under the plasma concentration-time curve (AUC0-∞) and the peak concentration (Cmax) of nifedipine were increased after oral and intravenous administration. Moreover, the absolute bioavailability (AB) and relative bioavailability (RB) of nifedipine in the presence of kaempferol was significantly higher than those of the control group after oral and intravenous administration. Improvement of bioavailability of nifedipine by kaempferol may be mainly because of the inhibition of the P-gp-mediated efflux transporter in the small intestine and CYP3A4-mediated metabolism in the small intestine or liver, or both.


Assuntos
Inibidores do Citocromo P-450 CYP3A/farmacologia , Quempferóis/farmacologia , Nifedipino/farmacocinética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Animais , Disponibilidade Biológica , Linhagem Celular , Citocromo P-450 CYP3A/metabolismo , Relação Dose-Resposta a Droga , Vias de Administração de Medicamentos , Humanos , Concentração Inibidora 50 , Masculino , Nifedipino/administração & dosagem , Nifedipino/análogos & derivados , Ratos Sprague-Dawley , Rodamina 123/metabolismo
10.
J Dairy Sci ; 102(11): 10573-10586, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31521364

RESUMO

Prostaglandin (PG) F2α and its analogs (aPGF2α) are used to induce regression of the corpus luteum (CL); their administration during the middle stage of the estrous cycle causes luteolysis in cattle. However, the bovine CL is resistant to the luteolytic actions of aPGF2α in the early stage of the estrous cycle. The mechanisms underlying this differential luteal sensitivity, as well as acquisition of luteolytic sensitivity by the CL, are still not fully understood. Therefore, to characterize possible differences in response to aPGF2α administration, we aimed to determine changes in expression of genes related to (1) angiogenesis-fibroblast growth factor 2 (FGF2), fibroblast growth factor receptor 1 (FGFR1), fibroblast growth factor receptor 2 (FGFR2), vascular endothelial growth factor A (VEGFA), vascular endothelial growth factor receptor 1 (VEGFR1), vascular endothelial growth factor receptor 2 (VEGFR2); and (2) steroidogenesis-steroidogenic acute regulatory protein (STAR), cytochrome P450 family 11 subfamily A member 1 (P450scc), and hydroxy-delta-5-steroid dehydrogenase, 3 ß- and steroid delta-isomerase 1 (HSD3B) in early- and middle-stage CL that accompany local (intra-CL) versus systemic (i.m.) aPGF2α injection. Cows at d 4 (early stage) or d 10 (middle stage) of the estrous cycle were treated as follows: (1) systemic saline injection, (2) systemic aPGF2α injection (25 mg), (3) local saline injection, and (4) local aPGF2α injection (2.5 mg). Progesterone (P4) concentration was measured in jugular vein blood samples during the entire set of experiments. After 4 h of treatment, CL were collected by ovariectomy, and mRNA and protein expression levels were determined by reverse transcription quantitative-PCR and Western blotting, respectively. Local and systemic aPGF2α injections upregulated FGF2 expression but decreased expression of VEGFA in both CL stages. Both aPGF2α injections increased the expression of STAR in early-stage CL, but downregulated it in middle-stage CL. In the early-stage CL, local administration of aPGF2α upregulated HSD3B, whereas systemic injection decreased its mRNA expression in early- and middle-stage CL. Moreover, we observed a decrease in the P4 level earlier after local aPGF2α injection than after systemic administration. These results indicate that aPGF2α acting locally may play a luteotrophic role in early-stage CL. The systemic effect of aPGF2α on the mRNA expression of genes participating in steroidogenesis seems to be more substantial than its local effect in middle-stage CL.


Assuntos
Indutores da Angiogênese/farmacologia , Corpo Lúteo/efeitos dos fármacos , Dinoprosta/farmacologia , Esteroides/biossíntese , Indutores da Angiogênese/administração & dosagem , Animais , Bovinos , Dinoprosta/administração & dosagem , Vias de Administração de Medicamentos/veterinária , Ciclo Estral , Feminino , Expressão Gênica/efeitos dos fármacos , Injeções/métodos , Injeções/veterinária , Peptídeos e Proteínas de Sinalização Intercelular/genética , Luteólise/efeitos dos fármacos , Fosfoproteínas , Progesterona/sangue
11.
Mycoses ; 62(11): 1049-1055, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31479538

RESUMO

Antifungal treatment options for allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitisation (SAFS) are largely limited to itraconazole based on the outcome of randomised controlled trials. It is unclear if nebulised amphotericin B deoxycholate (Fungizone® ) is a viable therapeutic option. We evaluated the safety and efficacy of nebulised Fungizone® in the long-term treatment of various forms of pulmonary aspergillosis. We assessed the records of 177 patients with various forms of pulmonary aspergillosis attending the National Aspergillosis Centre in Manchester who had received Fungizone® . Patients first received a challenge test with nebulised Fungizone® in hospital with spirometry pre/post-Fungizone® and nebulised salbutamol given pre-Fungizone® . Tolerability and changes in Aspergillus IgE, Aspergillus IgG and total IgE were evaluated. Sixty-six per cent (117/177) were able to tolerate the test dose of Fungizone® and in all cases, the reason for discontinuation of the first test dose was worsening breathlessness. Twenty six (21%) stopped therapy within 4-6 weeks, and the commonest reason cited for discontinuation of therapy was increased breathlessness, hoarseness and cough. Eighteen (10.2%) patients continued the Fungizone® for >3 months of which 5 (27.8%) recorded an improvement in total IgE, Aspergillus-specific IgE and Aspergillus IgG. Eleven had ABPA, four had SAFS, two had Aspergillus bronchitis and one had Aspergillus sensitisation with cavitating nodules. Among these 18 patients, sputum fungal culture results went from positive to negative in five patients, became positive in one patient, remained positive in three patients, and remained negative in seven patients. Nebulised Fungizone® appears to be a poorly tolerated treatment for pulmonary Aspergillosis with high dropout rates. There appears to be both clinical and serological benefits following sustained treatment with nebulised Fungizone® in some patients.


Assuntos
Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Ácido Desoxicólico/uso terapêutico , Adesão à Medicação/estatística & dados numéricos , Nebulizadores e Vaporizadores , Aspergilose Pulmonar/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anfotericina B/efeitos adversos , Anticorpos Antifúngicos/sangue , Antifúngicos/efeitos adversos , Aspergillus/efeitos dos fármacos , Ácido Desoxicólico/efeitos adversos , Vias de Administração de Medicamentos , Combinação de Medicamentos , Avaliação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Reino Unido , Adulto Jovem
12.
BMJ Case Rep ; 12(8)2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31420436

RESUMO

Fetal goitrous hypothyroidism is a rare entity and is caused mainly by maternal treatment of Graves' disease (GD). We report a case of a 22-year-old woman referred at 12 weeks of gestation due to hyperthyroidism subsequent to recently diagnosed GD. She started treatment with propylthiouracil and, at 21 weeks of gestation, fetal goitre was detected. A cordocentesis confirmed the diagnosis of fetal goitrous hypothyroidism, and intra-amniotic administration of levothyroxine (LT4) was performed and repeated through the pregnancy due to maintenance of fetal goitre. The pregnancy proceeded without further complications and a healthy female infant was born at 37 weeks of gestation, with visible goitre and thyroid function within the normal range at birth. Although there is no consensus on the optimal dose, the number of injections and the interval between them, intra-amniotic LT4 administration is recommended once fetal goitrous hypothyroidism is suspected, in order to prevent long-term complications of fetal hypothyroidism.


Assuntos
Doenças Fetais/tratamento farmacológico , Bócio/tratamento farmacológico , Doença de Graves/tratamento farmacológico , Hipotireoidismo/tratamento farmacológico , Tiroxina/administração & dosagem , Vias de Administração de Medicamentos , Feminino , Bócio/embriologia , Bócio/etiologia , Doença de Graves/complicações , Doença de Graves/embriologia , Humanos , Hipotireoidismo/embriologia , Hipotireoidismo/etiologia
13.
Medicine (Baltimore) ; 98(31): e16616, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31374027

RESUMO

BACKGROUND: To compare the efficacies of gonadotropin-releasing hormone (GnRH) pulse subcutaneous infusion with combined human chorionic gonadotropin and human menopausal gonadotropin (HCG/HMG) intramuscular injection have been performed to treat male hypogonadotropic hypogonadism (HH) spermatogenesis. METHODS: In total, 220 idiopathic/isolated HH patients were divided into the GnRH pulse therapy and HCG/HMG combined treatment groups (n = 103 and n = 117, respectively). The luteinizing hormone and follicle-stimulating hormone levels were monitored in the groups for the 1st week and monthly, as were the serum total testosterone level, testicular volume and spermatogenesis rate in monthly follow-up sessions. RESULTS: In the GnRH group and HCG/HMG group, the testosterone level and testicular volume at the 6-month follow-up session were significantly higher than were those before treatment. There were 62 patients (62/117, 52.99%) in the GnRH group and 26 patients in the HCG/HMG (26/103, 25.24%) group who produced sperm following treatment. The GnRH group (6.2 ±â€Š3.8 months) had a shorter sperm initial time than did the HCG/HMG group (10.9 ±â€Š3.5 months). The testosterone levels in the GnRH and HCG/HMG groups were 9.8 ±â€Š3.3 nmol/L and 14.8 ±â€Š8.8 nmol/L, respectively. CONCLUSION: The GnRH pulse subcutaneous infusion successfully treated male patients with HH, leading to earlier sperm production than that in the HCG/HMG-treated patients. GnRH pulse subcutaneous infusion is a preferred method.


Assuntos
Hormônio Liberador de Gonadotropina/uso terapêutico , Hipogonadismo/tratamento farmacológico , Substâncias para o Controle da Reprodução/uso terapêutico , Espermatogênese/efeitos dos fármacos , Adolescente , Adulto , Gonadotropina Coriônica/uso terapêutico , Vias de Administração de Medicamentos , Esquema de Medicação , Combinação de Medicamentos , Hormônio Foliculoestimulante/sangue , Hormônio Liberador de Gonadotropina/administração & dosagem , Humanos , Bombas de Infusão , Hormônio Luteinizante/sangue , Masculino , Menotropinas/uso terapêutico , Substâncias para o Controle da Reprodução/administração & dosagem , Testosterona/sangue , Adulto Jovem
14.
Rev Alerg Mex ; 66 Suppl 2: 1-39, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31443138

RESUMO

Anaphylaxis is a severe allergic reaction with a rapid onset and it is potentially life-threatening. Its clinical manifestations are varied; they may affect the skin, the cardiovascular system, the respiratory system, and the digestive system, among others. The treatment of choice, which is an intra-muscular injection of epinephrine (adrenaline), must be applied promptly. Therefore, being prepared to recognize it properly is of crucial importance. The objective of this clinical practice guide is to improve the knowledge of health professionals about anaphylaxis and, consequently, to optimize the treatment and long-term management of this reaction. This guide is adapted to the peculiarities of Latin America; especially in matters regarding the treatment. The need to introduce epinephrine auto-injectors in countries that don't have them yet is highlighted.


Assuntos
Anafilaxia , Guias de Prática Clínica como Assunto , Agonistas Adrenérgicos/administração & dosagem , Agonistas Adrenérgicos/uso terapêutico , Adulto , Algoritmos , Anafilaxia/diagnóstico , Anafilaxia/epidemiologia , Anafilaxia/etiologia , Anafilaxia/terapia , Reanimação Cardiopulmonar , Criança , Terapia Combinada , Gerenciamento Clínico , Vias de Administração de Medicamentos , Epinefrina/administração & dosagem , Epinefrina/uso terapêutico , Glucagon/administração & dosagem , Glucagon/uso terapêutico , Humanos , Testes Imunológicos , Educação de Pacientes como Assunto , Autoadministração , Vasoconstritores/administração & dosagem , Vasoconstritores/uso terapêutico
16.
Bone Joint J ; 101-B(7_Supple_C): 10-16, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31256650

RESUMO

AIMS: Tranexamic acid (TXA) is proven to reduce blood loss following total knee arthroplasty (TKA), but there are limited data on the impact of similar dosing regimens in revision TKA. The purpose of this multicentre randomized clinical trial was to determine the optimal regimen to maximize the blood-sparing properties of TXA in revision TKA. PATIENTS AND METHODS: From six-centres, 233 revision TKAs were randomized to one of four regimens: 1 g of intravenous (IV) TXA given prior to the skin incision, a double-dose regimen of 1 g IV TXA given both prior to skin incision and at time of wound closure, a combination of 1 g IV TXA given prior to skin incision and 1 g of intraoperative topical TXA, or three doses of 1950 mg oral TXA given two hours preoperatively, six hours postoperatively, and on the morning of postoperative day one. Randomization was performed based on the type of revision procedure to ensure equivalent distribution among groups. Power analysis determined that 40 patients per group were necessary to identify a 1 g/dl difference in the reduction of haemoglobin postoperatively between groups with an alpha of 0.05 and power of 0.80. Per-protocol analysis involved regression analysis and two one-sided t-tests for equivalence. RESULTS: In total, one patient withdrew, five did not undergo surgery, 16 were screening failures, and 25 did not receive the assigned treatment, leaving 186 patients for analysis. There was no significant difference in haemoglobin reduction among treatments (2.8 g/dl for single-dose IV TXA, 2.6 g/dl for double-dose IV TXA, 2.6 g/dl for combined IV/topical TXA, 2.9 g/dl for oral TXA; p = 0.38). Similarly, calculated blood loss (p = 0.65) and transfusion rates (p = 0.95) were not significantly different between groups. Equivalence testing assuming a 1 g/dl difference in haemoglobin change as clinically relevant showed that all possible pairings were statistically equivalent. CONCLUSION: Despite the higher risk of blood loss in revision TKA, all TXA regimens tested had equivalent blood-sparing properties. Surgeons should consider using the lowest effective dose and least costly TXA regimen in revision TKA. Cite this article: Bone Joint J 2019;101-B(Supple 7):10-16.


Assuntos
Artroplastia do Joelho/métodos , Perda Sanguínea Cirúrgica/prevenção & controle , Hemorragia Pós-Operatória/prevenção & controle , Ácido Tranexâmico/administração & dosagem , Antifibrinolíticos/administração & dosagem , Vias de Administração de Medicamentos , Feminino , Seguimentos , Hemoglobinas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Reoperação , Estudos Retrospectivos , Resultado do Tratamento
17.
Medicine (Baltimore) ; 98(30): e16570, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31348286

RESUMO

BACKGROUND: Perioperative bleeding during total knee arthroplasty (TKA) is an ongoing problem for surgeons. Intravenous or topical application of tranexamic acid (TXA) can effectively stop bleeding, but there is still no uniform standard for the best method of administration and dose. METHODS: From October 2016 to September 2018, 218 patients with unilateral primary knee osteoarthritis requiring knee replacement were enrolled and randomly divided into four groups. Group 1 (n = 55) received intra-articular injection (IAI) of TXA and peri-articular injection (PAI) of placebo, group 2 (n = 55) received IAI of placebo and PAI of TXA, group 3 (n = 51) received IAI of TXA and PAI of TXA, and group 4 (n = 57) received double placebo (IAI of placebo and PAI of placebo). The demographic characteristics, surgical indices, hematological indices, wound healing history, and thromboembolic events were investigated. RESULTS: Eight patients were lost to follow-up and 210 patients were included in the analysis. The median TBLs in patients who received IAI of TXA and PAI of placebo and those who received IAI of placebo and PAI of TXA were 470.81 ml and 481.54 ml, respectively. These TBL levels were significantly higher compared to those in patients who received IAI of TXA and PAI of TXA (359.18 ml, P ≤ .001), but significantly lower compared to those in patients who received the double placebo (522.71 ml, P ≤ .001). Compared to other groups, more patients in the double placebo group needed a blood transfusion (P = .013). In the short-term, the double placebo group had higher VAS pain scores and less ROM after surgery (P = .011 and P = .001, respectively). In the long-term (6-month follow-up), there were no significant differences in ROM, VAS, DVT, PE, or wound-related complications. CONCLUSION: The combined use of IAI and PAI of TXA can significantly reduce the TBL and the need for blood transfusion without delaying wound healing or increasing the risk of DVT and PE. In the short-term after surgery, this combined method reduces the pain VAS scores and improves the ROM; however, there are no long-term effects on VAS and ROM.


Assuntos
Antifibrinolíticos/uso terapêutico , Artroplastia do Joelho/métodos , Perda Sanguínea Cirúrgica/prevenção & controle , Ácido Tranexâmico/uso terapêutico , Fatores Etários , Idoso , Antifibrinolíticos/administração & dosagem , Transfusão de Sangue/estatística & dados numéricos , Índice de Massa Corporal , Relação Dose-Resposta a Droga , Método Duplo-Cego , Vias de Administração de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/cirurgia , Fatores Sexuais , Fatores Socioeconômicos , Tromboembolia/epidemiologia , Cicatrização/efeitos dos fármacos
18.
Photodiagnosis Photodyn Ther ; 27: 428-432, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31349099

RESUMO

Basal cell cancer (BCC) is an epithelial neoplasm that arises from basal cells, which constitute the lower layer of the epidermis. Global statistics have shown the progressive increase in the incidence of skin cancer in several countries. The cumulative exposure to solar radiation (ultraviolet B) in the first two decades of life represents the critical risk for the disease. Preclinical and clinical trials have shown photodynamic therapy (PDT) as a promising innovation for treatment of skin cancers, especially to the non-melanoma group. The authors reviewed trials with photodynamic therapy in superficial basal cell carcinoma with different photosensitizers to better evaluate how PDT modifies the natural history of sBCC. We conclude trials should not assess only the immediate efficacy but the main goal of long-term effectiveness of the protocols in order to generate best evidence for clinical practice.


Assuntos
Carcinoma Basocelular/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Vias de Administração de Medicamentos , Humanos , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Espécies Reativas de Oxigênio/metabolismo
19.
Regul Toxicol Pharmacol ; 107: 104415, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31254556

RESUMO

Nonclinical animal studies are considered as an integral part of biosimilar development program to demonstrate similarity and safety. We have compiled, reviewed and summarized animal studies conducted for European Medicines Agency (EMA) and United States Food and Drug Administration (US FDA) submission from 2006 till December 2018. The commonest animal studies conducted included repeat-dose toxicity study along with toxicokinetic, local tolerance and immunogenicity assessments, while the least common included primary pharmacodynamic, pharmacokinetic, safety pharmacology and single-dose toxicity studies. Animal studies were designed based on pharmacology of the drug, disease condition and innovator studies. Studies mostly used EU-sourced reference products as a comparator. For biosimilars approved both in the US and European Union (EU), similar data packages were submitted to these regions. Despite the regulatory guidelines allowing waiver of animal studies based on analytical data, animal studies have been conducted for almost all the approved biosimilars in the US and EU. There is an increasing need to re-assess the relevance of animal studies to support regulatory approval of biosimilars. Stepwise assessment for biosimilarity and conducting animal studies only if required at the right instance based on residual uncertainties may assist in optimizing animal study requirement for biosimilar development.


Assuntos
Medicamentos Biossimilares/toxicidade , Aprovação de Drogas , Animais , Formação de Anticorpos/efeitos dos fármacos , Medicamentos Biossimilares/administração & dosagem , Medicamentos Biossimilares/farmacocinética , Medicamentos Biossimilares/farmacologia , Vias de Administração de Medicamentos , Avaliação Pré-Clínica de Medicamentos
20.
J Vet Pharmacol Ther ; 42(4): 440-446, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31206720

RESUMO

Levosulpiride (LSP) is the l-enantiomer of sulpiride, and LSP recently replacing sulpiride in several EU countries. Several studies about LSP in humans are present in the literature, but neither pharmacodynamic nor pharmacokinetic data of LSP is present for veterinary species. The aim of this study was to assess the pharmacokinetic profile of LSP after intravenous (IV), intramuscular (IM), and oral (PO) administration in goats. Animals (n = 6) were treated with 50 mg LSP by IV, IM, and PO routes according to a randomized cross-over design (3 × 3 Latin-square). Blood samples were collected prior and up to 24 hr after LSP administration and quantified using a validated HPLC method with fluorescence detection. IV and IM administration gave similar concentration versus time curve profiles. The IM mean bioavailability was 66.97%. After PO administration, the drug plasma concentrations were detectable only in the time range 1.5-4 hr, and the bioavailability (4.73%) was low. When the AUC was related to the administered dose in mg/kg, there was a good correlation in the IV and IM groups, but very low correlation for the PO route. In conclusion, the IM and IV administrations result in very similar plasma concentrations. Oral dosing of LSP in goats is probably not viable as its oral bioavailability was very low.


Assuntos
Cabras/sangue , Sulpirida/análogos & derivados , Animais , Área Sob a Curva , Estudos Cross-Over , Antagonistas de Dopamina/administração & dosagem , Antagonistas de Dopamina/farmacocinética , Vias de Administração de Medicamentos , Feminino , Meia-Vida , Sulpirida/administração & dosagem , Sulpirida/farmacocinética
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