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1.
Clín. investig. ginecol. obstet. (Ed. impr.) ; 51(2): [100934], Abri-Jun, 2024. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-232730

RESUMO

Antecedentes: La pérdida gestacional precoz acontece en el 10-20% de todas las gestaciones clínicas, siendo el 85% previos a la semana 12 de amenorrea. El aborto involuntario conlleva una carga muy significativa en los recursos destinados a sanidad, alcanzado un coste económico nacional en Reino Unido de 471 millones de libras esterlinas por año (533,06 millones de euros), cifra extrapolable a otros países industrializados. Según una revisión sistemática reciente no hay ensayos bien diseñados en gestaciones del primer trimestre que arrojen una evidencia consolidada sobre cuál es el mejor método de tratamiento de aborto del primer trimestre y existen diferentes estudios que han tratado de evidenciar reducción de costes con resultados contradictorios. Material y métodos: Se realiza un estudio de diseño observacional, retrospectivo y longitudinal. Se revisaron 892 pacientes diagnosticadas de aborto espontáneo durante el primer trimestre de gestación, en el periodo comprendido entre enero de 2013 y diciembre de 2016. En nuestro estudio hemos querido evaluar la efectividad del misoprostol vaginal como tratamiento médico para el aborto espontáneo en el primer trimestre, en comparación con el legrado obstétrico/evacuador y, cuantificar la diferencia en los costos de ambos procedimientos a través de un estudio de minimización de costes. Resultados: De las 892 pacientes reclutadas, se realizó tratamiento médico con misoprostol en 517 (57,95%) y tratamiento quirúrgico mediante legrado evacuador en 375 (42,05%). La efectividad del tratamiento médico fue del 82% (426/517). Con respecto al tratamiento quirúrgico la efectividad resultó del 100%. La tasa de éxito del tratamiento médico fue superior en el subgrupo de pacientes con aborto incompleto (92,9%), en comparación con los grupos de gestación anembrionada (85,7%) y aborto diferido (78,2%). Conclusiones: El tratamiento médico del aborto es un manejo seguro y aceptado por las pacientes...(AU)


Background: Early pregnancy loss occurs in 10-20% of all clinical pregnancies, 85% being prior to week 12 of amenorrhea. Miscarriage entails a very significant burden on healthcare resources, reaching a national economic cost in the United Kingdom of £471 million per year (€533.06 million), a figure that can be extrapolated to other industrialized countries. According to a recent systematic review, there are no well-designed trials in first-trimester pregnancies that provide consolidated evidence on what is the best first-trimester abortion treatment method, and there are different studies that have tried to demonstrate cost reduction with contradictory results. Material and methods: An observational, retrospective and longitudinal design study was carried out. 892 patients diagnosed with spontaneous abortion during the first trimester of pregnancy were reviewed, in the period between January 2013 and December 2016. In our study, we wanted to evaluate the efficacy of vaginal misoprostol as a medical treatment for spontaneous abortion in the first trimester, in comparison with obstetric curettage-evacuator, and to quantify the difference in the costs of both procedures through a cost minimization study. costs. Results: Of the 892 recruited patients, medical treatment with misoprostol was performed in 517 (57.95%) and surgical treatment by curettage in 375 (42.05%). The effectiveness of medical treatment was 82% (426/517). With respect to surgical treatment the effectiveness of 100%. The success rate of medical treatment was higher in the subgroup of patients with incomplete abortion (92.9%), compared to the anembryonic gestation (85.7%) and delayed abortion (78.2%) groups. Conclusions: The medical treatment of abortion is a safe management and accepted by the patients. The adequate selection of candidate patients leads to an increase in the success rate and a decrease in costs...(AU)


Assuntos
Humanos , Feminino , Aborto Espontâneo/tratamento farmacológico , Resultado do Tratamento , Misoprostol/economia , Custos de Medicamentos , Aborto , Estudos Retrospectivos , Estudos Longitudinais
2.
Biomed Pharmacother ; 168: 115779, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37913737

RESUMO

BACKGROUND: The occurrence of liver abnormalities in Psoriatic Arthritis (PsA) has gained significant recognition. Identifying key factors at the clinical and molecular level can help to detect high-risk patients for non-alcoholic fatty liver disease in PsA. OBJECTIVES: to investigate the influence of PsA and cumulative doses of methotrexate on liver function through comprehensive in vivo and in vitro investigations. METHODS: A cross-sectional study involving 387 subjects was conducted, 200 patients with PsA, 87 NAFLD-non-PsA patients, and 100 healthy donors (HDs), age and sex-matched. Additionally, a retrospective longitudinal study was carried out, including 83 PsA patients since initiation with methotrexate. Detailed clinical, and laboratory parameters along with liver disease risk were analyzed. In vitro, experiments with hepatocyte cell line (HEPG2) were conducted. RESULTS: PsA patients present increased liver disease risk associated with the presence of cardiometabolic comorbidities, inflammatory markers, onychopathy, and psoriasis. The treatment with PsA serum on hepatocytes encompassed inflammatory, fibrotic, cell stress, and apoptotic processes. At the molecular level, methotrexate impacts liver biology, although the cumulative doses did not affect those alterations, causing any potential damage to liver function at the clinical level. Finally, anti-PDE-4 or anti-JAK decreased the inflammatory profile induced by PsA serum on hepatocytes. CONCLUSION: 1)This study identifies the complex link between liver disease risk, comorbidities, and disease-specific features in PsA patients. 2)Methotrexate dose in PsA patients had no significant effect on liver parameters, confirmed by hepatocyte in vitro studies. 3)Anti-PDE-4 and anti-JAK therapies show promise in reducing PsA serum-induced hepatocyte activation, potentially aiding liver complication management.


Assuntos
Artrite Psoriásica , Hepatopatia Gordurosa não Alcoólica , Psoríase , Humanos , Metotrexato/efeitos adversos , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/complicações , Artrite Psoriásica/epidemiologia , Estudos Retrospectivos , Estudos Longitudinais , Estudos Transversais , Psoríase/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente
3.
Eur J Intern Med ; 118: 49-58, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37544847

RESUMO

BACKGROUND: The aim of this study was to explore the impact of arthritis on liver function using different approaches in vivo and in vitro. METHODS: A cross-sectional study was performed on 330 non-obese/non-T2DM subjects: 180 RA patients, 50 NAFLD non-RA patients, and 100 healthy donors (HDs). A longitudinal study was conducted on 50 RA patients treated with methotrexate for six months. Clinical and laboratory parameters and markers of liver disease were collected. Mechanistic studies were carried out in both the CIA mouse model and hepatocytes treated with anti-citrullinated protein antibodies (ACPAs). RESULTS: RA patients have an increased risk of suffering from liver disease independent of obesity or T2DM. This risk was associated with factors such as insulin resistance, autoantibodies, inflammation, and component C3. Methotrexate treatment for six months was associated with liver abnormalities in those newly-diagnosed patients having CV risk factors. ACPAs induced a defective hepatocyte function, promoting IR and inflammation. The induction of arthritis in mice caused the infiltration of immune cells in the liver and increased inflammatory, apoptotic, and fibrotic processes. CONCLUSION: RA patients may experience mild to moderate liver inflammation due to the infiltration of T, B cells, and macrophages, and the action of ACPAs. This is independent of obesity or diabetes and linked to systemic inflammation, and disease activity levels. The negative effects of methotrexate on liver function could be restricted to the concomitant presence of cardiovascular risk factors.


Assuntos
Artrite Reumatoide , Hepatopatias , Humanos , Animais , Camundongos , Metotrexato/uso terapêutico , Estudos Longitudinais , Estudos Transversais , Peptídeos Cíclicos , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Autoanticorpos , Inflamação , Obesidade
4.
Rev. esp. investig. quir ; 25(2): 53-55, 2022. ilus
Artigo em Espanhol | IBECS | ID: ibc-204879

RESUMO

Mujer de 65 años derivada por autopalpación de nódulo mamario izquierdo que se confirma durante la exploración en consulta.Tras la realización de pruebas complementarias se diagnostica un carcinoma de mama bilateral: carcinoma infiltrante tipo NOSen mama izquierda y carcinoma in situ en mama derecha. Ambas axilas están libres de afectación ganglionar tanto clínica comoradiológicamente. Se realiza mastectomía bilateral con incisión en piel en forma de T invertida (Weiss) seguida de colocación deprótesis de poliuretano prepectoral bilateral y biospsia de ganglios centinelas que resultan negativos. Evolución postoperatoriafavorable. (AU)


A 65-year-old woman is referred for self-palpation of a left breast nodule which is confirmed during the examination at the clinic.Furhter testings confirm the diagnosis of bilateral breast carcinoma: NOS infiltrating carcinoma in the left breast and “in situ”carcinoma in the right one. Both axillas are clinically and radiologically negatives. Bilateral mastectomy is performed with invertedT-shaped skin incision (Weiss) followed by bilateral prepectoral prosthesis implant and bilateral sentinel node biopsy with negativeresults. Post-surgical evolution was unnoticed. (AU)


Assuntos
Humanos , Feminino , Idoso , Neoplasias da Mama , Neoplasias da Mama/cirurgia , Neoplasias da Mama/terapia , Procedimentos de Cirurgia Plástica , Implante Mamário
6.
Stem Cells Int ; 2019: 4541797, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31885608

RESUMO

Psoriasis is a skin disease characterized by hyperproliferation of keratinocytes and chronic inflammation. Mesenchymal stem/stromal cells (MSCs) exhibit an immunoregulatory function that can be altered in the skin of these patients. However, to date, the presence and functional capacity of MSCs in the dermis and epidermis of patients with psoriasis have not been fully established. In the present study, we evaluated the presence of MSCs in the skin of patients by obtaining adherent cells from the dermis and epidermis of lesional and nonlesional areas and characterizing them in a comparative manner with corresponding cells obtained from the dermis (HD-MSCs) and epidermis (HE-MSCs) of healthy donors. We determined whether the adherent cells had immunophenotypic profiles and differentiation potentials that were characteristic of MSCs. In addition, we analyzed their immunosuppression function by evaluating their capacity to decrease T cell proliferation. Our results indicate the presence of MSCs in the dermis and epidermis of healthy donors and patients with psoriasis; adherent cells from all skin sources exhibited MSC characteristics, such as expression of CD73, CD90, and CD105 markers and a lack of hematopoietic and endothelial marker expression. However, the cell populations obtained showed differences in differentiation potential toward adipogenic, osteogenic, and chondrogenic lineages. In addition, we observed a low MSC obtention frequency in nonlesional epidermal samples (NLE-MSCs), which also showed alterations in morphology and proliferation rate. Interestingly, MSCs from both the nonlesional dermis (NLD-MSCs) and lesional dermis (LD-MSCs) showed higher HLA class I antigen (HLA-I) expression than HD-MSCs. Moreover, NLD-MSCs showed a low T cell proliferation suppression capacity. In summary, this study demonstrates the presence of MSCs in the epidermis and dermis of patients with psoriasis and suggests that such cells may favor the inflammatory process and thus psoriatic lesion development through high HLA-I expression and low immunosuppression capacity.

7.
Rehabilitación (Madr., Ed. impr.) ; 52(2): 100-106, abr.-jun. 2018. ilus, tab, graf
Artigo em Espanhol | IBECS | ID: ibc-175684

RESUMO

Introducción: La espondiloartritis axial (EspAx) es una enfermedad reumática que afecta a toda la columna del paciente (lumbar, dorsal y cervical) y produce una reducción de la movilidad a medida que la enfermedad avanza. Diversas herramientas metrológicas se han propuesto para evaluar esta movilidad. El objetivo de nuestro estudio es evaluar el uso de sensores inerciales (Inertial Measuring Unit) como herramienta para la medición de la movilidad espinal en pacientes con EspAx. Material y método: Estudio descriptivo y transversal donde se define la movilidad espinal por el movimiento cervical y dorsolumbar en los planos frontal, lateral y trasversal. Se utilizaron 7 pacientes con EspAx y 7 individuos sanos como grupo control. La movilidad se midió de forma sincronizada con un sistema basado en sensores inerciales y otro sistema de captura de movimiento basado en vídeo (UCOTrack©). Además, se obtuvieron medidas de metrología convencional. Finalmente se calcularon índices compuestos basados en estas medidas: BASMI, UCOASMI e iUCOASMI. Resultados: Tanto las medidas individuales como el índice obtenido a partir de los sensores, iUCOASMI, presentaron buena fiabilidad y concordancia con coeficientes de correlación intraclase superiores a 0,7 (¿0,95 en el grupo de pacientes) y excelente correlación (p<0,01) con UCOASMI y BASMI. En un ajuste de correlación lineal de iUCOASMI/UCOASMI se obtuvo una R2 de 0,97. Discusión: Los resultados obtenidos indican que los sensores inerciales podrían ser útiles para analizar la movilidad espinal en pacientes con EspAx de forma más precisa y fiable que la metrología convencional, y más flexible y económica que otros sistemas avanzados


Introduction: Axial Spondyloarthritis (AxSpa) is a rheumatic disease that affects the entire spine of the patient (lumbar, dorsal and cervical) and produces a reduction of mobility as the disease progresses. Several metrological tools have been proposed to assess this mobility. The objective of our study is to evaluate the use of inertial sensors "Inertial Measuring Unit" (IMU) as a tool for the measurement of spinal mobility in patients with AxSpA. Material and method: Descriptive and transversal study where spinal mobility is defined by cervical and dorsal-lumbar movement in frontal, lateral and transverse planes; by means of non-probabilistic sampling, 7 patients with AxSpA and 7 healthy subjects were recruited as control group. Mobility was measured synchronously with a system based on inertial motion sensors (IMU) and another video-based motion capture system (UCOTrack©). In addition, measurements of conventional metrology. Finally the BASMI (Bath Ankylosing Spondylitis Metrology Index), UCOASMI (University of Cordoba Ankilosing Spondylitis Metrology Index) and iUCOASMI index were obtained. Results: Both the individual measures obtained with the IMU and the composite index obtained from these measures, the iUCOASMI, show good reliability and concordance with intraclass correlation coefficients (ICC) above .7 (ICC¿.95 in the patient group), and an excellent correlation (P<.01) between iUCOASMI with UCOASMI and BASMI. In an adjustment of linear correlation of iUCOASMI/UCOASMI a R2 of .97 was obtained. Discussion: Results obtained shown that inertial sensors could be useful for analyzing spinal mobility in patients with AxSpA in a more accurate and reliable way than conventional metrology, and more flexible and economical than other advanced systems


Assuntos
Humanos , Espondilartrite/fisiopatologia , Coluna Vertebral/fisiopatologia , Amplitude de Movimento Articular/fisiologia , Limitação da Mobilidade , Precisão da Medição Dimensional , 34860 , Estudos Transversais , Estudos de Casos e Controles , Sensibilidade e Especificidade
8.
J Intern Med ; 284(1): 61-77, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29532531

RESUMO

BACKGROUND: Rheumatoid arthritis (RA) patients are at increased risk of insulin resistance (IR); however, the specific mechanisms mediating this association are currently unknown. OBJECTIVE: To investigate whether the inflammatory activity associated with RA accounts for the observed defective glucose metabolism and lipid metabolism in these patients. METHODS: We followed two main strategies: (i) extensive metabolic profiling of a RA cohort of 100 patients and 50 healthy control subjects and (ii) mechanistic studies carried out in both a collagen-induced arthritis mouse model and 3T3-L1 adipocytes treated with conditioned serum from RA patients. RESULTS: Following the exclusion of obese and diabetic subjects, data from RA patients demonstrated a strong link between the degree of systemic inflammation and the development of IR. These results were strengthened by the observation that induction of arthritis in mice resulted in a global inflammatory state characterized by defective carbohydrate and lipid metabolism in different tissues. Adipose tissue was most susceptible to the RA-induced metabolic alterations. These metabolic effects were confirmed in adipocytes treated with serum from RA patients. CONCLUSIONS: Our results show that the metabolic disturbances associated with RA depend on the degree of inflammation and identify inflammation of adipose tissue as the initial target leading to IR and the associated molecular disorders of carbohydrate and lipid homeostasis. Thus, we anticipate that therapeutic strategies based on tighter control of inflammation and flares could provide promising approaches to normalize and/or prevent metabolic alterations associated with RA.


Assuntos
Artrite Reumatoide/sangue , Glicemia/metabolismo , Inflamação/sangue , Lipídeos/sangue , Células 3T3-L1 , Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Adulto , Idoso , Animais , Artrite Experimental/sangue , Estudos de Casos e Controles , Doença Crônica , Estudos de Coortes , Feminino , Humanos , Resistência à Insulina/fisiologia , Masculino , Camundongos , Pessoa de Meia-Idade
9.
J Autoimmun ; 82: 31-40, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28465139

RESUMO

OBJECTIVES: 1) To assess the association of NETosis and NETosis-derived products with the activity of the disease and the development of cardiovascular disease in RA; 2) To evaluate the involvement of NETosis on the effects of biologic therapies such as anti-TNF alpha (Infliximab) and anti-IL6R drugs (Tocilizumab). METHODS: One hundred and six RA patients and 40 healthy donors were evaluated for the occurrence of NETosis. Carotid-intimae media thickness was analyzed as early atherosclerosis marker. Inflammatory and oxidative stress mediators were quantified in plasma and neutrophils. Two additional cohorts of 75 RA patients, treated either with Infliximab (n = 55) or Tocilizumab (n = 20) for six months, were evaluated. RESULTS: NETosis was found increased in RA patients, beside myeloperoxidase and neutrophil elastase protein levels. Cell-free nucleosomes plasma levels were elevated, and strongly correlated with the activity of the disease and the positivity for autoantibodies, alongside inflammatory and oxidative profiles in plasma and neutrophils. Moreover, ROC analyses showed that cell-free nucleosomes levels could identify RA patients showing early atherosclerosis with high specificity. RA patients treated either with IFX or TCZ for six months exhibited decreased generation of NETs. Concomitantly, clinical parameters and serum markers of inflammation were found reduced. Mechanistic in vitro analyses showed that inhibition of NETs extrusion by either DNase, IFX or TCZ, further abridged the endothelial dysfunction and the activation of immune cells, thus influencing the global activity of the vascular system. CONCLUSIONS: NETosis-derived products may have diagnostic potential for disease activity and atherosclerosis, as well as for the assessment of therapeutic effectiveness in RA.


Assuntos
Artrite Reumatoide/complicações , Aterosclerose/diagnóstico , Aterosclerose/etiologia , Armadilhas Extracelulares/metabolismo , Idoso , Antirreumáticos/uso terapêutico , Aterosclerose/terapia , Biomarcadores , Estudos de Casos e Controles , Comorbidade , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Interleucina-6/antagonistas & inibidores , Interleucina-6/metabolismo , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Peroxidase , Curva ROC , Fatores de Risco , Índice de Gravidade de Doença , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/metabolismo
10.
Rheumatol Int ; 36(12): 1627-1632, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27778067

RESUMO

To analyse the cost-effectiveness, in daily clinical practice, of the strategy of treating to the target of clinical remission (CR) in patients with established rheumatoid arthritis (RA), after 2 years of treatment with biological therapy. Adult patients with established RA were treated with biological therapy and followed up for 2 years by a multidisciplinary team responsible for their clinical management. Treatment effectiveness was evaluated by the DAS28 score. The direct costs incurred during this period were quantified from the perspective of the healthcare system. We calculated the cost-effectiveness of obtaining a DAS28 < 2.6, considered as CR. The study included 144 RA patients treated with biological therapies. After 2 years of treatment, 32.6% of patients achieved CR. The mean cost of achieving CR at 2 years was 79,681 ± 38,880 euros. The strategy of treatment to the target of CR is considered the most effective, but in actual clinical practice in patients with established RA, it has a high cost.


Assuntos
Antirreumáticos/economia , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/economia , Análise Custo-Benefício , Adulto , Antirreumáticos/uso terapêutico , Artrite Reumatoide/economia , Produtos Biológicos/uso terapêutico , Bases de Dados Factuais , Feminino , Custos de Cuidados de Saúde , Humanos , Masculino , Metotrexato/economia , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Indução de Remissão , Índice de Gravidade de Doença , Sulfassalazina/economia , Sulfassalazina/uso terapêutico , Resultado do Tratamento
11.
BMC Musculoskelet Disord ; 17(1): 382, 2016 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-27596243

RESUMO

BACKGROUND: Several measurements are often used in daily clinical practice in the assessment of Ankylosing Spondylitis (AS) patients. The Assessment in SpondyloArthiritis International Society (ASAS) recommend in its core set: chest expansion modified Schöber test, Occiput to wall distance, lateral lumbar flexion, cervical rotation and The Bath Ankylosing Spondylitis Metrology Index (BASMI). BASMI also includes five measurements, some of them recommended by ASAS. Three versions of BASMI have been published with different scales and intervals for each component of the index. Though studies about reliability of these measurements are needed. The aim of this study was to analyze inter-rater reliability of recommended spinal mobility measures in AS. METHODS: We examined reproducibility of spinal mobility measurements on 33 AS patients performed by two experienced rheumatologists in the same day. Descriptive statistics, Intraclass Correlation Coefficients (ICC), and Smallest Detectable Difference (SDD) using the Bland-Altman criteria were obtained for all the measurements. RESULTS: Chest expansion showed the lowest value of ICC (0.66) and occiput-wall the highest (0.97). SDD was 2.43 units for BASMI2 and 1.27 units for BASMI10. CONCLUSIONS: Reliability according to ICC was moderate to high in all measurements. BASMI10, instead BASMI2, must be used: measurements used to calculate are the same but there is better reliability. Inter-rater variation, expressed as SDD, must be taken in account: smaller improvements do not demonstrate the efficacy of treatment because they can be due to experimental error and not to the treatment itself.


Assuntos
Espondilite Anquilosante/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Exame Físico/métodos , Espondilite Anquilosante/fisiopatologia
12.
Sci Rep ; 6: 31375, 2016 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-27502756

RESUMO

MicroRNAs markedly affect the immune system, and have a relevant role in CVD and autoimmune diseases. Yet, no study has analyzed their involvement in atherothrombosis related to APS and SLE patients. This study intended to: 1) identify and characterize microRNAs linked to CVD in APS and SLE; 2) assess the effects of specific autoantibodies. Six microRNAs, involved in atherothrombosis development, were quantified in purified leukocytes from 23 APS and 64 SLE patients, and 56 healthy donors. Levels of microRNAs in neutrophils were lower in APS and SLE than in healthy donors. Gene and protein expression of miRNA biogenesis-related molecules were also reduced. Accordingly, more than 75% of identified miRNAs by miRNA profiling were underexpressed. In monocytes, miR124a and -125a were low, while miR-146a and miR-155 appeared elevated. Altered microRNAs' expression was linked to autoimmunity, thrombosis, early atherosclerosis, and oxidative stress in both pathologies. In vitro treatment of neutrophils, monocytes, and ECs with aPL-IgG or anti-dsDNA-IgG antibodies deregulated microRNAs expression, and decreased miRNA biogenesis-related proteins. Monocyte transfections with pre-miR-124a and/or -125a caused reduction in atherothrombosis-related target molecules. In conclusion, microRNA biogenesis, significantly altered in neutrophils of APS and SLE patients, is associated to their atherothrombotic status, further modulated by specific autoantibodies.


Assuntos
Síndrome Antifosfolipídica/sangue , Lúpus Eritematoso Sistêmico/sangue , MicroRNAs/sangue , Trombose/sangue , Adulto , Autoanticorpos/sangue , Biomarcadores/metabolismo , Espessura Intima-Media Carotídea , Estudos de Casos e Controles , Biologia Computacional , Epigênese Genética , Feminino , Humanos , Imunoglobulina G/sangue , Inflamação , Leucócitos/citologia , Masculino , Pessoa de Meia-Idade , Monócitos/citologia , Neutrófilos/metabolismo , Estresse Oxidativo , Transfecção
15.
Rheumatol Int ; 36(2): 231-41, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26494567

RESUMO

Biological drugs have proven efficacy and effectiveness in treatment of rheumatoid arthritis (RA), although none has been shown to be superior. Few studies have evaluated the cost-effectiveness of biological drugs in real-life clinical conditions. The objective of this study was to compare the cost-effectiveness of infliximab, etanercept and adalimumab in achieving clinical remission (DAS28 < 2.6) when used as initial biological therapy. Patients were diagnosed with RA who began treatment with infliximab, etanercept or adalimumab in the Reina Sofia Hospital (Cordoba, Spain) between January 1, 2007, and December 31, 2012. Effectiveness was measured as the percentage of patients who achieved clinical remission after 2 years. The cost analysis considered the use of direct health resources (perspective of the healthcare system). Cost-effectiveness was calculated by dividing the total mean cost of each treatment by the percentage of patients who achieved remission. One hundred and thirty patients were included: 55 with infliximab, 44 with adalimumab and 31 with etanercept. After 2 years, 45.2 % of patients with adalimumab achieved clinical remission, versus 29.1 % with infliximab (p = 0.133) and 22.7 % with etanercept (p = 0.040), with no differences between etanercept and infliximab (p = 0.475). The average total cost at 2 years was €29,858, €25,329 and €23,309 for adalimumab, infliximab and etanercept, respectively, while the mean cost (95 %CI) to achieve remission was €66,057 (48,038­84,076), €87,040 (78,496­95,584) and €102,683 (94,559­110,807), respectively. Adalimumab was more efficient than etanercept (p < 0.001) and infliximab (p = 0.026), with no differences between etanercept and infliximab (p = 0.086). Adalimumab was the most cost-effective treatment in achieving clinical remission in real-life clinical conditions in RA patients during the study period.


Assuntos
Adalimumab/economia , Adalimumab/uso terapêutico , Antirreumáticos/economia , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/economia , Custos de Medicamentos , Etanercepte/economia , Etanercepte/uso terapêutico , Infliximab/economia , Infliximab/uso terapêutico , Adalimumab/efeitos adversos , Adulto , Idoso , Antirreumáticos/efeitos adversos , Artrite Reumatoide/diagnóstico , Redução de Custos , Análise Custo-Benefício , Etanercepte/efeitos adversos , Feminino , Humanos , Infliximab/efeitos adversos , Masculino , Pessoa de Meia-Idade , Modelos Econômicos , Sistema de Registros , Indução de Remissão , Espanha , Fatores de Tempo , Resultado do Tratamento
16.
Phys Rev Lett ; 115(10): 102503, 2015 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-26382674

RESUMO

The antineutrino spectra measured in recent experiments at reactors are inconsistent with calculations based on the conversion of integral beta spectra recorded at the ILL reactor. (92)Rb makes the dominant contribution to the reactor antineutrino spectrum in the 5-8 MeV range but its decay properties are in question. We have studied (92)Rb decay with total absorption spectroscopy. Previously unobserved beta feeding was seen in the 4.5-5.5 region and the GS to GS feeding was found to be 87.5(25)%. The impact on the reactor antineutrino spectra calculated with the summation method is shown and discussed.

17.
Phys Rev Lett ; 115(6): 062502, 2015 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-26296113

RESUMO

Total absorption spectroscopy is used to investigate the ß-decay intensity to states above the neutron separation energy followed by γ-ray emission in (87,88)Br and (94)Rb. Accurate results are obtained thanks to a careful control of systematic errors. An unexpectedly large γ intensity is observed in all three cases extending well beyond the excitation energy region where neutron penetration is hindered by low neutron energy. The γ branching as a function of excitation energy is compared to Hauser-Feshbach model calculations. For (87)Br and (88)Br the γ branching reaches 57% and 20%, respectively, and could be explained as a nuclear structure effect. Some of the states populated in the daughter can only decay through the emission of a large orbital angular momentum neutron with a strongly reduced barrier penetrability. In the case of neutron-rich (94)Rb the observed 4.5% branching is much larger than the calculations performed with standard nuclear statistical model parameters, even after proper correction for fluctuation effects on individual transition widths. The difference can be reconciled by introducing an enhancement of 1 order of magnitude in the photon strength to neutron strength ratio. An increase in the photon strength function of such magnitude for very neutron-rich nuclei, if it proves to be correct, leads to a similar increase in the (n,γ) cross section that would have an impact on r process abundance calculations.

19.
Cell Stress Chaperones ; 20(3): 461-72, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25618331

RESUMO

Heat shock protein 72 (Hsp72) protects cells against a variety of stressors, and multiple studies have suggested that Hsp72 plays a cardioprotective role. As skeletal muscle Hsp72 overexpression can protect against high-fat diet (HFD)-induced insulin resistance, alterations in substrate metabolism may be a mechanism by which Hsp72 is cardioprotective. We investigated the impact of transgenically overexpressing (Hsp72 Tg) or deleting Hsp72 (Hsp72 KO) on various aspects of cardiac metabolism. Mice were fed a normal chow (NC) or HFD for 12 weeks from 8 weeks of age to examine the impact of diet-induced obesity on metabolic parameters in the heart. The HFD resulted in an increase in cardiac fatty acid oxidation and a decrease in cardiac glucose oxidation and insulin-stimulated cardiac glucose clearance; however, there was no difference in Hsp72 Tg or Hsp72 KO mice in these rates compared with their respective wild-type control mice. Although HFD-induced cardiac insulin resistance was not rescued in the Hsp72 Tg mice, it was preserved in the skeletal muscle, suggesting tissue-specific effects of Hsp72 overexpression on substrate metabolism. Comparison of two different strains of mice (BALB/c vs. C57BL/6J) also identified strain-specific differences in regard to HFD-induced cardiac lipid accumulation and insulin resistance. These strain differences suggest that cardiac lipid accumulation can be dissociated from cardiac insulin resistance. Our study finds that genetic manipulation of Hsp72 does not lead to alterations in metabolic processes in cardiac tissue under resting conditions, but identifies mouse strain-specific differences in cardiac lipid accumulation and insulin-stimulated glucose clearance.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Proteínas de Choque Térmico HSP72/metabolismo , Cardiopatias/metabolismo , Animais , Composição Corporal , Comportamento Alimentar , Glucose/metabolismo , Proteínas de Choque Térmico HSP72/genética , Cardiopatias/etiologia , Resistência à Insulina , Metabolismo dos Lipídeos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Oxirredução , Ácido Palmítico/metabolismo
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