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1.
Drug Discov Ther ; 14(1): 14-20, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32147626

RESUMO

We compared the pharmaceutical properties, such as surface tension, drop volume, nozzle inner diameter, and force to push the drug product out of the container (squeeze force), of purified sodium hyaluronate eye drops preparations of one brand-name (Hyalein) and 11 generic drugs used for treatment of keratoconjunctiva epithelial disorders, and examined product selection based on the needs of the patient. The surface tension of Nissin (51.0 dyn/cm) and Nitten (52.3 dyn/cm) was significantly lower than that of Hyalein (62.8 dyn/cm), whereas Nitten PF (69.5 dyn/cm) was significantly higher than Hyalein. The drop volume of Tearbalance (42.4 mg), Nissin (43.7 mg), and Nitten (42.7 mg) was significantly lower than that of Hyalein (50.4 mg). We compared the squeeze force using a wearable touch sensor (Haptic Skill Logger: HapLog®) and digital force gauge (DF). The squeeze force of HapLog® showed values of about 1.7- to 3.5-fold higher than that of DF. Moreover, the squeeze force of Eyecare (34.0 N), Kyorin (35.4 N), and Nitten PF (44.3 N) by HapLog® was significantly higher than that of Hyalein (10.5 N). In contrast, the squeeze force of Kyorin (20.8 N) and Nitten PF (25.0 N) by DF was significantly higher than that of Hyalein (12.2 N). Two questionnaire surveys on the feeling of instillation of eye drops revealed a strong negative correlation between feeling of use and squeeze force.


Assuntos
Avaliação de Medicamentos , Soluções Oftálmicas , Avaliação de Medicamentos/normas , Medicamentos Genéricos/normas , Humanos , Soluções Oftálmicas/normas , Satisfação do Paciente , Dispositivos Eletrônicos Vestíveis
2.
World Neurosurg ; 133: e385-e390, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31521761

RESUMO

BACKGROUND: Optimal management of patients with extracranial blunt cerebrovascular injury (BCVI) remains controversial, with both anticoagulation and antiplatelet therapy being recommended. The purpose of this study was to evaluate the efficacy and safety of using acetylsalicylic acid (ASA) in the management of BCVI. METHODS: Patients with BCVI were identified from the registry of a Level 1 trauma center between 2010 and 2017. Digital imaging and electronic medical records were reviewed for patient information including demographic characteristics, injury type, therapy, outcomes, and follow-up. RESULTS: Over the study period, 13,578 patients were admitted following blunt trauma, with 94 (0.7%) having confirmed BCVI (mean age, 42 years; 72% male). Mean Injury Severity Score and Glasgow Coma Score were 27 and 10, respectively. BCVI was identified in 130 vessels with Biffl grade I (38%) and grade II injury (29%) being most common. Twelve (13%) patients experienced an ischemic event, but only 3 events occurred after diagnosis. ASA was primary treatment for 56 (60%) patients. Thirty patients (32%) received no treatment; 21 patients died within 24 hours of primary injury. Only 4 patients had ASA contraindications. Four patients (7%) had ASA-related complications; there were 2 cases of intracranial hemorrhage progression and 2 cases of gastrointestinal bleeding. Follow-up vascular imaging at a mean of 36 days demonstrated stable or improved levels of BCVI in 94% of patients. CONCLUSIONS: An ASA-based management strategy for BCVI was efficacious and relatively safe in this study. This approach may be the preferred treatment for BCVI, but confirmation is needed.


Assuntos
Aspirina/uso terapêutico , Traumatismo Cerebrovascular/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Ferimentos não Penetrantes/tratamento farmacológico , Adolescente , Adulto , Idoso , Aneurisma Dissecante/etiologia , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Aspirina/efeitos adversos , Lesões das Artérias Carótidas/tratamento farmacológico , Artéria Carótida Interna , Traumatismo Cerebrovascular/complicações , Traumatismo Cerebrovascular/epidemiologia , Gerenciamento Clínico , Avaliação de Medicamentos , Feminino , Hemorragia/induzido quimicamente , Mortalidade Hospitalar , Humanos , Escala de Gravidade do Ferimento , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Traumatismo Múltiplo/epidemiologia , Inibidores da Agregação de Plaquetas/efeitos adversos , Estudos Retrospectivos , Acidente Vascular Cerebral/etiologia , Artéria Vertebral/lesões , Ferimentos não Penetrantes/complicações , Ferimentos não Penetrantes/epidemiologia , Adulto Jovem
4.
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
5.
Arch. Soc. Esp. Oftalmol ; 94(9): 430-435, sept. 2019. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-186221

RESUMO

Objetivo: Evaluar los resultados visuales y anatómicos de aflibercept en pacientes naïve con degeneración macular asociada a la edad neovascular (DMAEnv) no seleccionados tras un año de tratamiento en régimen bimestral fijo en un entorno de práctica clínica real. Métodos: Estudio retrospectivo, serie de casos consecutivos no aleatorizados que incluye 35 pacientes naïve, 38 ojos con DMAEnv, tratados con aflibercept intravítreo (Eylea(R)). Los pacientes recibieron una dosis de carga de 3 inyecciones mensuales (2 mg/0,05 ml) seguida de inyecciones cada 2 meses. Resultados: Tras la dosis de carga y a los 12 meses de tratamiento, el cambio en la mejor agudeza visual corregida (MAVC) mejoró significativamente respecto a la MAVC basal (ETDRS 50,5 ± 14,5 y 53,1 ± 14,5 vs. 39,6 ± 14,7, respectivamente, p < 0,05). Al mes 3 y al mes 12, la proporción de pacientes que mejoró la agudeza visual en ≥ 15 letras fue de 37,1% y de 45,7%, respectivamente. La disminución media del espesor central de la retina fue también significativa tras la dosis de carga (239,6 ± 52,0 μm) y al mes 12 (227 ± 53,2μm) comparada con los valores pretratamiento (370,3 ± 117,6; p < 0,001). También se observó la resolución del desprendimiento del epitelio pigmentario en 14 de los 20 ojos (70%) con ese desprendimiento previo al tratamiento. Conclusión: Mejorías funcionales y anatómicas significativas fueron observadas tras el tratamiento con aflibercept intravítreo en pacientes naïve con DMAEnv en práctica clínica real


Objective: To investigate the visual and anatomical outcomes of aflibercept as therapy in patients with treatment-naïve neovascular age-related macular degeneration during one year in routine clinical practice. Methods: The study was a retrospective, case series, including 35 patients, 38 eyes, with neovascular age-related macular degeneration that received aflibercept injections (Eylea(R)). Patients received a loading dose of 3 monthly injections (2 mg / 0.05 ml) followed by intravitreal injections every 2 months. Results: At 3 and 12 months, the mean best-corrected visual acuity improved significantly as compared with baseline (ETDRS 50.5 ± 14.5 and 53.1 ± 14.5 vs. 39.6 ± 14.7, respectively, P < .05). At 3 and 12 months, the proportion of patients who improved visual acuity by ≥ 15 letters was 37.1% and 45.7%, respectively. The mean decrease in central macular thickness was also significant after loading dose (239.6 ± 52.0μm) and at 12 month (227 ± 53.2 μm) compared with pre-treatment values (370.3 ± 117, 6) (P < .001). Resolution of pigment epithelial detachment (PED) was also observed in 14 out of 20 (70%) eyes with PED at baseline. Conclusion: Aflibercept administered by fixed dosing over one year improved visual acuity and macular morphology in treatment-naïve eyes in routine daily practice


Assuntos
Humanos , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/uso terapêutico , Degeneração Macular/tratamento farmacológico , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Avaliação de Medicamentos , Seguimentos , Macula Lutea/patologia , Degeneração Macular/patologia , Descolamento Retiniano/tratamento farmacológico , Descolamento Retiniano/etiologia , Hemorragia Retiniana/etiologia , Epitélio Pigmentado da Retina/patologia , Estudos Retrospectivos , Resultado do Tratamento , Acuidade Visual
6.
Endodoncia (Madr.) ; 37(2): 8-20, sept. 2019. graf
Artigo em Espanhol | IBECS | ID: ibc-186295

RESUMO

Objetivos. Los objetivos de este son: 1. Evaluar el consumo de medicamentos, así como la automedicación entre los individuos que acuden a realizarse una endodoncia. 2.Evaluar la mejoría de sintomatología tras la toma de medicación. 3. Evaluar la ansiedad dental entre los pacientes sometidos a tratamiento endodóntico previo a la intervención. Material y Métodos: Se realizó un estudio de tipo observacional, transversal y comparativo, consistente en una encuesta sobre pacientes mayores de 16 años que acudieron a una clínica universitaria odontológica. Resultados: Se recopilaron 167 encuestas entre septiembre de 2017 y marzo del 2018, siendo válidas 131 y no válidas 36, cuyos resultados más destacados fueron los siguientes: · Ingesta de antibióticos + analgésicos y/o AINES (40,6%)· Ingesta analgésicos y/o AINES (59,4%). Origen de esa medicación; 44,6% prescrita por el odontólogo, seguida del 42,7% que corresponde a la tomada por decisión propia, 10,8% al médico de cabecera, 2,7% a urgencias y 0% al farmacéutico y de origen homeopático. Media de ansiedad en la escala de 4,38. La media de ansiedad en mujeres: 5 y en hombres: 3,2 (p: 0.0066). Grupo con algún tipo de formación académica; media de ansiedad: 4,24 y grupo sin ningún estudio; media de ansiedad: 8,75 (p: 0.0144). Conclusiones: Los pacientes encuestados tenían una alta tendencia a la automedicación, utilizándose fundamentalmente analgésicos y/o AINES. Además, referían mejoría en el día de la intervención tras haber tomado algún tipo de medicamento. Los pacientes encuestados sufrieron un grado de ansiedad medio previo a la realización del tratamiento endodóntico


Objectives: The objectives of this study are: 1. To evaluate the consumption of medicines as well as self-medication among the individuals who undergo endodontics.2. To evaluate the improvement of symptoms after taking medication. 3. To evaluate dental anxiety among patients undergoing endodontic treatment prior to the intervention. Material and Methods: An observational, transversal and comparative study was carried out, consisting of a survey of patients over 16 years of age who attended a university dental clinic. Results: In this study 167 surveys were collected, between September 2017 and March 2018, with 131 valid and 36 invalid. Taking antibiotics + analgesics and/or NSAIDs (40.6%) and analgesics and/or NSAIDs (59.4%); Origin of that medication; 44.6% prescribed by the dentist, followed by the 42.7% prescribed by the dentist, 10.8% by the general practitioner, 2.7% by the emergency department and 0% by the pharmacist and homeopathic origin. Average anxiety on the 4.38 scale. Average anxiety in women: 5 and in men: 3.2 (p: 0.0066).Group with some type of academic training; mean anxiety: 4.24 and group without any study; mean anxiety: 8.75 (p: 0.0144). Conclusions: The patients surveyed had a high tendency to self-medication, mainly using analgesics and/or NSAIDs. They also reported improvement on the day of the intervention after having taken some type of medication. The patients surveyed suffered a medium degree of anxiety prior to the endodontic treatment


Assuntos
Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Automedicação/tendências , Ansiedade/psicologia , Endodontia/métodos , Avaliação de Medicamentos/métodos , Sobremedicalização , Estudos Transversais , Resistência a Medicamentos , Epidemiologia Descritiva , Pulpite/tratamento farmacológico , Inquéritos e Questionários
7.
Pediatr Blood Cancer ; 66(11): e27953, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31393093

RESUMO

BACKGROUND: Pediatric patients with high-risk, relapsed, or refractory solid tumors have a poor prognosis. We have previously reported a dose-finding experience of high-dose chemotherapy consisting of thiotepa and melphalan ("double-conditioning regimen"). Using doses derived from that study, we have treated patients since 2005. We now report a retrospective review of patients treated by this fixed dose. PROCEDURE: We reviewed 50 patients (median 4 years; range 0-15 years) with high-risk or relapsed/refractory solid tumors treated by this dose-fixed, double-conditioning regimen from April 2005 to May 2014. Doses were thiotepa 800 mg/m2 and melphalan 280 mg/m2 for children ≥2 years of age, and 32 mg/kg and 6 mg/kg, respectively, for children <2 years of age. Further, doses were reduced according to creatinine clearance with poor renal function. RESULTS: Nonhematological toxicity was mainly gastrointestinal-grade 3 mucositis (n = 41) and grade 3-4 diarrhea (n = 10). Neurological, renal, and endothelial cell toxicity and sinusoidal obstruction syndrome were not observed. There were two toxic deaths (interstitial viral pneumonia). This regimen demonstrated antitumor activity against several types of tumors. Although the frequency of gastrointestinal toxicity was high, other severe toxicity was not observed. CONCLUSIONS: Our double-conditioning regimen was very well tolerated and demonstrated antitumor activity. We are moving forward with multi-institutional trials now.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias/terapia , Transplante de Células-Tronco de Sangue Periférico , Terapia de Salvação , Condicionamento Pré-Transplante/métodos , Adolescente , Criança , Pré-Escolar , Terapia Combinada , Creatinina/sangue , Relação Dose-Resposta a Droga , Avaliação de Medicamentos , Estudos de Viabilidade , Feminino , Seguimentos , Gastroenteropatias/induzido quimicamente , Doenças Hematológicas/induzido quimicamente , Humanos , Lactente , Recém-Nascido , Doenças Pulmonares Intersticiais/etiologia , Masculino , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Neoplasias/tratamento farmacológico , Pneumonia Viral/etiologia , Estudos Retrospectivos , Risco , Tiotepa/administração & dosagem , Tiotepa/efeitos adversos , Condicionamento Pré-Transplante/efeitos adversos , Transplante Autólogo
8.
Biologicals ; 61: 38-43, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31416791

RESUMO

Tremendous efforts are being made to develop an anthrax vaccine with long term protection. The main component of traditional anthrax vaccine is protective antigen (PA) with the trace amount of other proteins and bacterial components. In this study, we developed a recombinant PA-LF chimera antigen of Bacillus anthracis by fusing the PA domain 2-4 with lethal factor (LF) domain 1 and evaluated its protective potential against B. anthracis in mouse model. The anti-PA-LF chimera serum reacted with both PA and LF antigen, individually. The chimera elicited a strong antibody titer in mice with predominance of IgG1 isotype followed by IgG2b, IgG2a and IgG3. Cytokines were assessed in splenocytes of immunized mice and a significant up-regulation in the expression of IL-4, IL-10, IFN-γ and TNF-α was observed. The PA-LF chimera immunized mice exhibited 80% survival after challenge with virulent spores of B. anthracis. Pathological studies showed normal architecture in vital organs (spleen, lung, liver and kidney) of recovered immunized mice on 20 DPI after spore challenge. These findings suggested that PA-LF chimera of B. anthracis elicited good humoral as well as cell mediated immune response in mice, and thus, can be a potent vaccine candidate against anthrax.


Assuntos
Vacinas contra Antraz/imunologia , Antraz/prevenção & controle , Antígenos de Bactérias/imunologia , Bacillus anthracis/imunologia , Toxinas Bacterianas/imunologia , Proteínas Recombinantes de Fusão/imunologia , Animais , Antraz/imunologia , Antraz/patologia , Vacinas contra Antraz/genética , Antígenos de Bactérias/genética , Bacillus anthracis/genética , Toxinas Bacterianas/genética , Gerenciamento Clínico , Avaliação de Medicamentos , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Recombinantes de Fusão/genética
9.
Phytother Res ; 33(11): 2841-2848, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31429148

RESUMO

Maintaining glycemic control in diabetes and prediabetes is necessary to prevent many health complications and mortality. Although different hypoglycemic drugs are used for this purpose, there is still a growing interest in the use of medicinal plants due to their low price, easy availability, and fewer or no side effects. Moringa (Moringa oleifera Lam.) is a medicinal plant that has been traditionally used in the management of diabetes. This review aims to present the existing literature published until February 2019 on the role of moringa leaves in glycemia and their physiological mechanisms. In the conducted studies, moringa leaves have shown to reduce glycemia, without causing any adverse effects. The proposed mechanisms for reducing glycemia include inhibition of α-amylase and α-glucosidase activities, increased glucose uptake in the muscles and liver, inhibition of glucose uptake from the intestine, decreased gluconeogenesis in the liver, and increased insulin secretion and sensitivity. However, these studies are limited in numbers and mostly conducted in animals, in vitro and in vivo. Therefore, long-term human studies are required to determine the hypoglycemic effect of moringa leaves, their physiological mechanisms, active ingredients, and safety. Overall, this review provides evidence that moringa leaves have the possibility to be used as a glycemic control agent in diabetes and prediabetes.


Assuntos
Glicemia/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Moringa oleifera/química , Extratos Vegetais/farmacologia , Animais , Glicemia/metabolismo , Diabetes Mellitus/sangue , Diabetes Mellitus/tratamento farmacológico , Avaliação de Medicamentos/estatística & dados numéricos , Humanos , Hipoglicemiantes/uso terapêutico , Fígado/efeitos dos fármacos , Fitoterapia/métodos , Extratos Vegetais/uso terapêutico , Folhas de Planta/química , Plantas Medicinais/química , Estado Pré-Diabético/sangue , Estado Pré-Diabético/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos
10.
Hematol Oncol ; 37(4): 345-351, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31283840

RESUMO

Based on results of two pilot trials, lenalidomide (LEN) was found to be active and safe as monotherapy and showed an increased response rate of 80% in combination with rituximab (R) for patients with mucosa-associated lymphoid tissue (MALT) lymphoma. While initial results were promising, there are currently no data on long-term outcome, and larger international phase II/III trials on LEN for indolent lymphoma lack specific subgroup analyses. Thus, we have systematically analyzed 50 patients treated with LEN-based therapy (LEN-monotherapy n = 16, R-LEN n = 34) at the Medical University of Vienna 2009 to 2019 and investigated long-term outcome and relapse patterns. At a follow-up of more than 5 years (median 68 months), 54% of patients are free of relapse, and estimated median progression-free survival (PFS) was 72 months (95%CI 49-96). There was no difference in PFS according to stage of disease, i.e. localized versus disseminated disease (P = .67) and previous systemic treatment (P = .16). Interestingly, but with the caveat of the limited number of patients included in this series, primary extragastric disease had a superior PFS compared with gastric lymphoma (P = .04) and also depth of response, i.e. complete or partial response versus stable disease was associated with significantly prolonged PFS (P = .01). We documented four patients (8%) with pronounced improvement of response during follow-up including three patients initially rated as partial remission and finally achieving complete remission at 12 to 32 months. This highlights the potential of delayed responses to LEN treatment. Estimated overall survival at 5 years was excellent at 92%. These "real-world" data confirm long-term activity of LEN in MALT lymphoma.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Antineoplásicos/uso terapêutico , Fatores Imunológicos/uso terapêutico , Lenalidomida/uso terapêutico , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/administração & dosagem , Antineoplásicos/administração & dosagem , Áustria/epidemiologia , Avaliação de Medicamentos , Feminino , Seguimentos , Humanos , Fatores Imunológicos/administração & dosagem , Estimativa de Kaplan-Meier , Lenalidomida/administração & dosagem , Linfoma de Zona Marginal Tipo Células B/epidemiologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/epidemiologia , Intervalo Livre de Progressão , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento
12.
Pediatr Blood Cancer ; 66(11): e27948, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31347788

RESUMO

BACKGROUND: Despite the intensity of hematopoietic stem cell transplantation (HCT), relapse remains the most common cause of death in juvenile myelomonocytic leukemia (JMML). In contrast to other leukemias where therapy is used to reduce leukemic burden prior to transplant, many patients with JMML proceed directly to HCT with active disease. The objective of this study was to elucidate whether pre-HCT therapy has an effect on the molecular burden of disease and how this affects outcome post-HCT. PROCEDURE: Twenty-one patients with JMML who received pre-HCT therapy and were transplanted at UCSF were analyzed in this study. The mutant allele frequency of the driver mutation was assessed before and after pre-HCT therapy, using custom amplicon next-generation sequencing. RESULTS: Of the 21 patients, seven patients (33%) responded to therapy with a significant reduction in their mutant allele frequency and were classified as molecular responders. Six of these patients received moderate-intensity chemotherapy, one patient received only azacitidine. The 5-year progression-free survival after HCT of molecular responders was 100% versus 61% for nonresponders (P = .12). Survival of molecular nonresponders was not improved by use of high-intensity conditioning, but patients were salvaged if they experienced severe graft versus host disease. There were no baseline clinical characteristics that were associated with response to pre-HCT therapy. CONCLUSIONS: Despite the myelodysplastic nature of JMML, patients treated with pre-HCT therapy can achieve molecular remissions. These patients experienced a trend toward improved outcomes post-HCT. Importantly, molecular testing can be helpful to distinguish between responders and nonresponders and should become an integral part of clinical care.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Genes Neoplásicos , Transplante de Células-Tronco Hematopoéticas , Leucemia Mielomonocítica Juvenil/tratamento farmacológico , Terapia Neoadjuvante , Análise de Sequência de DNA , Carga Tumoral/efeitos dos fármacos , Antimetabólitos Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , Terapia Combinada , DNA de Neoplasias/sangue , Avaliação de Medicamentos , Monitoramento de Medicamentos , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/terapia , Humanos , Lactente , Leucemia Mielomonocítica Juvenil/sangue , Leucemia Mielomonocítica Juvenil/genética , Leucemia Mielomonocítica Juvenil/terapia , Masculino , Proteínas de Neoplasias/genética , Intervalo Livre de Progressão , Recidiva , Estudos Retrospectivos , Esplenectomia , Condicionamento Pré-Transplante
13.
Arch. Soc. Esp. Oftalmol ; 94(7): 347-351, jul. 2019. ilus, tab, video
Artigo em Espanhol | IBECS | ID: ibc-185190

RESUMO

La queratitis numular es un proceso inflamatorio de la córnea que se caracteriza por múltiples depósitos subepiteliales y para la cual se han propuesto diversas aproximaciones terapéuticas. Se realizó una revisión retrospectiva de las historias clínicas de pacientes diagnosticados con queratitis numular entre los años 2009 y 2017, que incluyó 21 ojos de 16 pacientes tratados con una inyección intraestromal combinada de ganciclovir y betametasona de depósito. Al finalizar el tratamiento, 18 ojos (85,71%) estaban asintomáticos. Esta mejora se mantuvo durante un tiempo medio de seguimiento de 22,90 meses. La combinación de betametasona de depósito mezclada con ganciclovir mediante aplicación intraestromal es una buena alternativa para el tratamiento de la queratitis numular


Nummular keratitis is an inflammatory process of the cornea that is characterised by multiple sub-epithelial deposits, for which a variety of therapeutic approaches have been proposed. A retrospective review was performed using the medical records of patients diagnosed with nummular keratitis and treated with a combined intrastromal injection of ganciclovir and depot betamethasone between the years 2009 and 2017. A total of 21 eyes of 16 patients were finally included. Upon termination of the treatment, 18 eyes (85.71%) were asymptomatic. This improvement was maintained during a mean follow-up time of 22.90 months. Depot betamethasone mixed with ganciclovir by intrastromal application is a good alternative for the treatment of nummular keratitis


Assuntos
Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Betametasona/uso terapêutico , Ganciclovir/uso terapêutico , Ceratite/tratamento farmacológico , Betametasona/administração & dosagem , Substância Própria , Preparações de Ação Retardada , Avaliação de Medicamentos , Quimioterapia Combinada , Seguimentos , Ganciclovir/administração & dosagem , Injeções Intraoculares , Estudos Retrospectivos , Resultado do Tratamento
14.
Arch Soc Esp Oftalmol ; 94(9): 430-435, 2019 Sep.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31182243

RESUMO

OBJECTIVE: To investigate the visual and anatomical outcomes of aflibercept as therapy in patients with treatment-naïve neovascular age-related macular degeneration during one year in routine clinical practice. METHODS: The study was a retrospective, case series, including 35 patients, 38 eyes, with neovascular age-related macular degeneration that received aflibercept injections (Eylea®). Patients received a loading dose of 3monthly injections (2mg / 0.05ml) followed by intravitreal injections every 2 months. RESULTS: At 3 and 12 months, the mean best-corrected visual acuity improved significantly as compared with baseline (ETDRS 50.5±14.5 and 53.1±14.5 vs. 39.6±14.7, respectively, P<.05). At 3 and 12 months, the proportion of patients who improved visual acuity by ≥15 letters was 37.1% and 45.7%, respectively. The mean decrease in central macular thickness was also significant after loading dose (239.6±52.0µm) and at 12 month (227±53.2µm) compared with pre-treatment values (370.3±117, 6) (P<.001). Resolution of pigment epithelial detachment (PED) was also observed in 14 out of 20 (70%) eyes with PED at baseline. CONCLUSION: Aflibercept administered by fixed dosing over one year improved visual acuity and macular morphology in treatment-naïve eyes in routine daily practice.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Degeneração Macular/tratamento farmacológico , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Avaliação de Medicamentos , Feminino , Seguimentos , Humanos , Macula Lutea/patologia , Degeneração Macular/patologia , Masculino , Descolamento Retiniano/tratamento farmacológico , Descolamento Retiniano/etiologia , Hemorragia Retiniana/etiologia , Epitélio Pigmentado da Retina/patologia , Estudos Retrospectivos , Resultado do Tratamento , Acuidade Visual
15.
Hematology ; 24(1): 516-520, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31242816

RESUMO

Objective: Anemia and thrombocytopenia are the most frequently reported adverse events of ruxolitinib in patients with MPN-associated myelofibrosis (MPN-MF). Although thalidomide, androgens and prednisone have previously demonstrated improvements in myelofibrosis-associated anemia, it is unclear whether these drugs are effective in patients taking ruxolitinib. Method: We conducted a retrospective cohort study to evaluate the efficacy and tolerability of combination therapy with low dose thalidomide, stanozolol and prednisone (TSP) in patients with IPSS intermediate-2 or high-risk myelofibrosis (MF) who received ruxolitinib treatment. Results: Sixty-five patients with MPN-MF who took ruxolitinib were enrolled in this retrospective study, of which 46 patients also took TSP while 19 did not take TSP (TSP and non-TSP groups). Within the first 24 weeks, the proportion of patients with anemia response and platelet count increase ≥50 × 109/L were 45.7% and 67.4% in the TSP group as compared to 0% and 10.5% in the non-TSP group (p < 0.001). The mean hemoglobin level in the non-TSP group reached the nadir after approximately 12-16 weeks of therapy, but gradually increased in the TSP group. Conclusion: In summary, TSP regimen can improve anemia and thrombocytopenia during ruxolitinib treatment in patients with MPN-MF, and the associated adverse events were manageable.


Assuntos
Anemia/induzido quimicamente , Prednisona/uso terapêutico , Mielofibrose Primária/tratamento farmacológico , Pirazóis/efeitos adversos , Esplenomegalia/prevenção & controle , Estanozolol/uso terapêutico , Talidomida/uso terapêutico , Trombocitopenia/induzido quimicamente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/sangue , Anemia/prevenção & controle , Anemia/terapia , Contagem de Células Sanguíneas , Transfusão de Sangue , Avaliação de Medicamentos , Quimioterapia Combinada , Feminino , Hemoglobinas/análise , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/complicações , Prednisona/administração & dosagem , Mielofibrose Primária/sangue , Mielofibrose Primária/etiologia , Pirazóis/administração & dosagem , Pirazóis/uso terapêutico , Estudos Retrospectivos , Esplenomegalia/etiologia , Esplenomegalia/patologia , Estanozolol/administração & dosagem , Talidomida/administração & dosagem , Trombocitopenia/sangue , Trombocitopenia/prevenção & controle
16.
Sanid. mil ; 75(2): 94-97, abr.-jun. 2019.
Artigo em Espanhol | IBECS | ID: ibc-183711

RESUMO

Se reseñan los medicamentos evaluados y con dictamen positivo por comisión de expertos de la Agencia Española de Medicamentos y Productos Sanitarios o de la Agencia Europea del Medicamento hechos públicos en diciembre de 2018, enero y febrero de 2019, y considerados de mayor interés para el profesional sanitario. Se trata de opiniones técnicas positivas que son previas a la autorización y puesta en el mercado del medicamento


The drugs assessed by the Spanish Agency for Medicines and Health Products or European Medicines Agency made public in December 2018, January and February of 2019 , and considered of interest to the healthcare professional, are reviewed. These are positive technical reports prior to the authorization and placing on the market of the product


Assuntos
Humanos , Avaliação de Medicamentos/métodos , Aprovação de Drogas/métodos , Avaliação de Medicamentos/instrumentação , Analgésicos
17.
Rev Gastroenterol Peru ; 39(1): 45-54, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31042236

RESUMO

OBJECTIVE: The ideal therapy for chronic hepatitis C is the use of direct acting antivirals (DAA). In Peru there is no data in this aspect, in that sense it is necessary to report real life experience with these drugs. MATERIAL AND METHODS: A digital survey was sent through e-mail to hepatologists, and the data of four is considered in this study. Statistical analysis was descriptive. RESULTS: We included 63 patients, mean age was 59 years, 49.21% were male, cirrhosis was present in 49.21%, and 34.92% was non-responder to PEGIFN and Ribavirin. Genotype 1 was present in 93.65%, and subtype 1a was 58.73%, there were only 2 cases with Gt 2 and one with Gt 3. There were 10 different DAA combinations used, and the most effective were Sofosbuvir/Ledipasvir, Sofosbuvir/Ledipasvir/Ribavirina and Sofosbuvir/Simeprevir, in all these cases the Sustained Viral Response (SVR) was 100%. The other combinations had SVR < 90% or only 1-2 patients included. All patients tolerated treatments and no serious adverse events occurred. CONCLUSIONS: In real life antiviral treatment for hepatitis C with AAD is effective and well tolerated. The best SVR was obtained with Sofosbuvir/Ledipasvir, Sofosbuvir/Ledipasvir/Ribavirina and Sofosbuvir/Simeprevir. This report may be useful to consider treatment strategies with focus in public health.


Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/administração & dosagem , Avaliação de Medicamentos , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Hepatite C Crônica/complicações , Hepatite C Crônica/virologia , Humanos , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Peru , Resultado do Tratamento , Adulto Jovem
18.
Cells ; 8(5)2019 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-31137590

RESUMO

Patient-derived tumor organoids (PDOs) represent a promising preclinical cancer model that better replicates disease, compared with traditional cell culture models. We have established PDOs from various human tumors to accurately and efficiently recapitulate the tissue architecture and function. Molecular targeted therapies with remarkable efficacy are currently in use against various tumors. Thus, there is a need for in vitro functional-potency assays that can be used to test the efficacy of molecular targeted drugs and model complex interactions between immune cells and tumor cells to evaluate the potential for cancer immunotherapy. This study represents an in vitro evaluation of different classes of molecular targeted drugs, including small-molecule inhibitors, monoclonal antibodies, and an antibody-drug conjugate, using lung PDOs. We evaluated epidermal growth factor receptor and human epidermal growth factor receptor 2 (HER2) inhibitors using a suitable high-throughput assay system. Next, the antibody-dependent cellular cytotoxicity (ADCC) activity of an anti-HER2 monoclonal antibody was evaluated to visualize the interactions of immune cells with PDOs during ADCC responses. Moreover, an evaluation system was developed for the immune checkpoint inhibitors, nivolumab and pembrolizumab, using PDOs. Our results demonstrate that the in vitro assay systems using PDOs were suitable for evaluating molecular targeted drugs under conditions that better reflect pathological conditions.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma Adenoescamoso/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Avaliação de Medicamentos/métodos , Neoplasias Pulmonares/tratamento farmacológico , Terapia de Alvo Molecular , Organoides/efeitos dos fármacos , Anticorpos Monoclonais Humanizados/farmacologia , Antineoplásicos/farmacologia , Biópsia , Carcinoma Adenoescamoso/patologia , Carcinoma Adenoescamoso/cirurgia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Receptores ErbB/antagonistas & inibidores , Humanos , L-Lactato Desidrogenase/análise , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Receptor ErbB-2/antagonistas & inibidores
19.
Future Oncol ; 15(19): 2227-2239, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31137964

RESUMO

P110-γ and -δ act in lymphocytes chemotaxis, presenting distinct, nonredundant roles in B- and T-cell migration and adhesion to stromal cells. Moreover, phosphoinositide-3-kinase-γ inhibition contributes to regulate macrophage polarization inhibiting cancer growth. Duvelisib (IPI-145) is an oral first-in-class, dual phosphoinositide-3-kinase inhibitor targeting p110-δ/γ exerting its activity in preclinical studies across different prognostic groups. In a large Phase III study, duvelisib showed superior progression-free survival and overall response rate compared with ofatumumab, thus leading to its approval for relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma. Immune-related effects are the main reason for treatment suspension, thus affecting survival benefit. Nevertheless, the correct management of adverse events, eventually including dose modification, allows patients to remain on treatment. In conclusion, duvelisib represents a promising treatment in chronic lymphocytic leukemia and a salvage therapy after ibrutinib.


Assuntos
Isoquinolinas/administração & dosagem , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Purinas/administração & dosagem , Pirazóis/administração & dosagem , Pirimidinas/administração & dosagem , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Classe I de Fosfatidilinositol 3-Quinases/antagonistas & inibidores , Classe I de Fosfatidilinositol 3-Quinases/genética , Avaliação de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/classificação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Humanos , Isoquinolinas/efeitos adversos , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/patologia , Masculino , Pessoa de Meia-Idade , Fosfatidilinositol 3-Quinases/genética , Prognóstico , Purinas/efeitos adversos , Pirazóis/efeitos adversos , Pirimidinas/efeitos adversos , Terapia de Salvação/efeitos adversos
20.
J Agric Food Chem ; 67(22): 6387-6396, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31090403

RESUMO

Insect chitinolytic ß- N-acetylhexosaminidase OfHex1, from the agricultural pest Ostrinia furnacalis (Guenée), is considered as a potential target for green pesticide design. In this study, rational molecular design and optimization led to the synthesis of compounds 15r ( Ki = 5.3 µM) and 15y ( Ki = 2.7 µM) that had superior activity against OfHex1 than previously reported lead compounds. Both compounds 15r and 15y had high selectivity toward OfHex1 over human ß- N-acetylhexosaminidase B (HsHexB) and human O-GlcNAcase (hOGA). In addition, to investigate the basis for the potency of glycosylated naphthalimides against OfHex1, molecular docking and molecular dynamics simulations were performed to study possible binding modes. Furthermore, the in vivo biological activity of target compounds with efficient OfHex1 inhibitory potency was assayed against Myzus persicae, Plutella xylostella, and O. furnacalis. This present work indicates that glycosylated naphthalimides can be further developed as potential pest control and management agents targeting OfHex1.


Assuntos
Inibidores Enzimáticos/síntese química , Proteínas de Insetos/antagonistas & inibidores , Inseticidas/síntese química , Mariposas/enzimologia , Naftalimidas/síntese química , beta-N-Acetil-Hexosaminidases/antagonistas & inibidores , Animais , Avaliação de Medicamentos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Glicosilação , Humanos , Proteínas de Insetos/química , Inseticidas/química , Inseticidas/farmacologia , Cinética , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Mariposas/efeitos dos fármacos , Naftalimidas/química , Naftalimidas/farmacologia , beta-N-Acetil-Hexosaminidases/química
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