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1.
Eur J Rheumatol ; 6(2): 81-84, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31365341

RESUMO

OBJECTIVE: To study the levels of rituximab (RTX) and anti-RTX antibodies (ARAs) in patients with rheumatoid arthritis (RA) at 30, 90, and 180 days after the first infusion, in relation to clinical and serological parameters and B cell homeostasis. METHODS: Thirty-four patients with RA who failed to respond to anti-tumor necrosis factor therapy received RTX. At baseline, 4, 12, and 24 weeks after the first infusion of RTX, we performed a clinical assessment and determined the levels of RTX, ARAs, B cells, rheumatoid factors, anti-cyclic citrullinated peptide antibodies, immunoglobulins, and complements. RESULTS: RTX levels varied widely among patients. No ARAs were detected during the follow-up. Patients with lower levels of RTX presented with higher decreases in erythrocyte sedimentation rate, immunoglobulins, and complement 6 months after the first infusion. Patients with higher levels of RTX showed a higher B cell depletion at 90 days but an earlier B cell recovery than those with lower levels of RTX. No differences in clinical response were observed between the two groups at 6 months after starting the treatment. CONCLUSION: Our findings suggest that RTX levels in the serum of patients with RA are related to B cell homeostasis and the severity of immunological parameters but not to the clinical response at 6 months.

2.
J Hosp Med ; 14(12): 737-745, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31339840

RESUMO

BACKGROUND: Hospitalized patients are frequently treated with opioids for pain control, and receipt of opioids at hospital discharge may increase the risk of future chronic opioid use. OBJECTIVE: To compare inpatient analgesic prescribing patterns and patients' perception of pain control in the United States and non-US hospitals. DESIGN: Cross-sectional observational study. SETTING: Four hospitals in the US and seven in seven other countries. PARTICIPANTS: Medical inpatients reporting pain. MEASUREMENTS: Opioid analgesics dispensed during the first 24-36 hours of hospitalization and at discharge; assessments and beliefs about pain. RESULTS: We acquired completed surveys for 981 patients, 503 of 719 patients in the US and 478 of 590 patients in other countries. After adjusting for confounding factors, we found that more US patients were given opioids during their hospitalization compared with patients in other countries, regardless of whether they did or did not report taking opioids prior to admission (92% vs 70% and 71% vs 41%, respectively; P < .05), and similar trends were seen for opioids prescribed at discharge. Patient satisfaction, beliefs, and expectations about pain control differed between patients in the US and other sites. LIMITATIONS: Limited number of sites and patients/country. CONCLUSIONS: In the hospitals we sampled, our data suggest that physicians in the US may prescribe opioids more frequently during patients' hospitalizations and at discharge than their colleagues in other countries, and patients have different beliefs and expectations about pain control. Efforts to curb the opioid epidemic likely need to include addressing inpatient analgesic prescribing practices and patients' expectations regarding pain control.

4.
Injury ; 49(12): 2198-2202, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30274759

RESUMO

INTRODUCTION: Centenarians and nonagenarians constitute a rapidly growing age group in Western countries and they are expected to be admitted to hospital with hip fractures. The aim of this study was to compare outcomes of centenarian and nonagenarian patients following a hip fracture and to identify risk factors related to in-hospital and post-discharge mortality in both groups. PATIENTS AND METHODS: A prospective evaluation of centenarian patients and nonagenarian controls admitted to a tertiary university hospital in Barcelona with hip fractures over a period of 5 years and 9 months. Baseline characteristics and outcomes in both patient groups were compared. Variables associated with in-hospital, 30-day, 3-month and 1-year mortality were also analyzed. RESULTS: Thirty-three centenarians and 82 nonagenarians were included. The most relevant statistically significant differences found were: Barthel index at admission (61.90 vs. 75.22), number of drugs before admission (4.21vs 5.55), in-hospital complication rates (97 vs. 78%), readmissions at 3 months and 1 year (0 vs 11.7% and 3.4 vs. 19.5% respectively) and mortality at 3 months and 1 year (41.4 vs. 20.8% and 62.1 vs. 29.9%, respectively). Mean number of complications, rapid atrial fibrillation, mean age, and urinary tract infection were risk factors associated with mortality. CONCLUSIONS: Centenarian patients had similar in-hospital outcomes to nonagenarians, but experienced more complications and twice the 3-month and 1-year mortality rate. The mean number of complications was the risk factor most consistently related to in-hospital and post-discharge mortality. These findings emphasize the need to improve care in very old patients to prevent complications.


Assuntos
Avaliação Geriátrica , Fraturas do Quadril/mortalidade , Tempo de Internação/estatística & dados numéricos , Atividades Cotidianas , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Estudos Prospectivos , Fatores de Risco , Espanha/epidemiologia , Taxa de Sobrevida
5.
J Gerontol A Biol Sci Med Sci ; 73(10): 1424-1428, 2018 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-29590357

RESUMO

Background: Patients older than 95 years of age can be categorized according to three morbidity profiles: escapers, delayers, and survivors. The aim of this study was to describe the baseline characteristics, in-hospital outcomes, and cumulative mortality of extremely elderly patients admitted with hip fractures and to examine whether there were differences between patients without age-related illnesses (escapers) and others in the same age group (survivors when age-associated illnesses were diagnosed before the age of 80, delayers when these illnesses appeared after the age of 80). Methods: A retrospective review of clinical and outcome data of all patients older than 95 years of age admitted with hip fractures. Results: Two hundred patients older than 95 years were admitted with hip fractures between December 2009 and September 2015. Eighty-six per cent of patients had at least one in-hospital complication. In-hospital mortality was 12.5 per cent; cumulative mortality rates at 30 days, 3 months, and 1 year were 20.3, 30.8, and 50.5 per cent, respectively. There were 15 (7.5%) escaper patients. Compared with other patients with age-related illnesses, they took fewer drugs, had lower Charlson scores, a higher Barthel index score, shorter length of hospital stay, less delay in surgery, and more often required discharge to an in-patient rehabilitation facility. No differences in cumulative mortality were noted. Conclusions: Escaper patients had better baseline characteristics, shorter length of hospital stay, and delay in surgery. Nevertheless, their in-hospital and cumulative mortality rates were similar to those of other patients older than 95 years.


Assuntos
Fraturas do Quadril/terapia , Atividades Cotidianas , Fatores Etários , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/mortalidade , Humanos , Tempo de Internação , Masculino , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Espanha/epidemiologia , Resultado do Tratamento
8.
Bone ; 90: 1-6, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27241279

RESUMO

Osteoporosis is a common multifactorial disorder characterized by low bone mass and reduced bone strength that may cause fragility fractures. In recent years, there have been substantial advancements in the biochemical monitoring of bone metabolism through the measurement of bone turnover markers. Currently, good knowledge of the genetics of such markers has become an indispensable part of osteoporosis research. In this study, we used the Genetic Analysis of Osteoporosis Project to study the genetics of the plasma levels of 12 markers related to bone metabolism and osteoporosis. Plasma phenotypes were determined through biochemical assays and log-transformed values were used together with a set of covariates to model genetic and environmental contributions to phenotypic variation, thus estimating the heritability of each trait. In addition, we studied correlations between the 12 markers and a wide variety of previously described densitometric traits. All of the 12 bone metabolism markers showed significant heritability, ranging from 0.194 for osteocalcin to 0.516 for sclerostin after correcting for covariate effects. Strong genetic correlations were observed between osteocalcin and several bone mineral densitometric traits, a finding with potentially useful diagnostic applications. In addition, suggestive genetic correlations with densitometric traits were observed for leptin and sclerostin. Overall, the few strong and several suggestive genetic correlations point out the existence of a complex underlying genetic architecture for bone metabolism plasma phenotypes and provide a strong motivation for pursuing novel whole-genome gene-mapping strategies.


Assuntos
Biomarcadores/sangue , Osso e Ossos/metabolismo , Densitometria , Característica Quantitativa Herdável , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Remodelação Óssea , Criança , Pré-Escolar , Família , Feminino , Humanos , Padrões de Herança/genética , Masculino , Pessoa de Meia-Idade , Fenótipo , Espanha , Adulto Jovem
10.
PLoS One ; 11(5): e0154833, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27163365

RESUMO

Femoral neck geometry parameters are believed to be as good as bone mineral density as independent factors in predicting hip fracture risk. This study was conducted to analyze the roles of genetic and environmental factors in femoral properties measured in a sample of Spanish families with osteoporotic fractures and extended genealogy. The "Genetic Analysis of Osteoporosis (GAO) Project" involved 11 extended families with a total number of 376 individuals. We studied three categorical phenotypes of particular clinical interest and we used a Hip structural analysis based on DXA to analyze 17 strength and geometrical phenotypes of the hip. All the femoral properties had highly significant heritability, ranging from 0.252 to 0.586. The most significant correlations were observed at the genetic level (ρG). Osteoporotic fracture status (Affected 2) and, particularly, low bone mass and osteoporotic condition (Affected 3) had the highest number of significant genetic correlations with diverse femoral properties. In conclusion, our findings suggest that a relatively simple and easy to use method based on DXA studies can provide useful data on properties of the Hip in clinical practice. Furthermore, our results provide a strong motivation for further studies in order to improve the understanding of the pathophysiological mechanism underlying bone architecture and the genetics of osteoporosis.


Assuntos
Fraturas do Colo Femoral/diagnóstico por imagem , Fraturas do Colo Femoral/genética , Colo do Fêmur/diagnóstico por imagem , Osteoporose Pós-Menopausa/diagnóstico por imagem , Osteoporose Pós-Menopausa/genética , Absorciometria de Fóton , Idoso , Densidade Óssea , Família , Feminino , Fraturas do Colo Femoral/patologia , Colo do Fêmur/metabolismo , Colo do Fêmur/patologia , Humanos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/patologia , Linhagem , Fenótipo , Prognóstico , Risco
11.
Pharmacogenomics ; 17(1): 25-9, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26652611

RESUMO

BACKGROUND: Methotrexate (MTX) is the most used drug for the treatment of rheumatoid arthritis (RA) although outcome differs among patients. AIM: To evaluate whether polymorphisms in pharmacokinetic genes are associated with outcome in RA patients receiving MTX. PATIENTS & METHODS: We analyzed 28 SNPs in SLC19A1/RFC1, ABCB1, FPGS and GGH genes. RESULTS: We studied 194 RA patients receiving MTX monotherapy. Two FPGS SNPs, rs10987742 and rs10106, were associated with response (p = 0.033 and p = 0.041, respectively). The FPGS rs10106 variant was also associated with MTX survival (p = 0.005) and toxicity (p = 0.021). Three ABCB1 SNPs, rs868755, rs10280623 and rs1858923, were associated with toxicity (p = 0.025, p = 0.048 and p = 0.031, respectively). CONCLUSION: FPGS and ABCB1 genetic variants can influence the outcome in RA patients receiving MTX monotherapy.


Assuntos
Anti-Inflamatórios não Esteroides/farmacocinética , Artrite Reumatoide/tratamento farmacológico , Metotrexato/farmacocinética , Polimorfismo de Nucleotídeo Único , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Adulto , Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite Reumatoide/genética , Artrite Reumatoide/fisiopatologia , Feminino , Glucosidases/genética , Humanos , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Peptídeo Sintases/genética , Proteína Carregadora de Folato Reduzido/genética
12.
Cardiovasc Res ; 106(1): 19-31, 2015 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-25538153

RESUMO

AIMS: Oxidative stress mediated by reactive oxygen species (ROS) plays a striking role in the pathogenesis of heart failure, and antioxidants have been shown to attenuate cardiac remodelling in experimental models of cardiac damage. We recently showed that fibroblast growth factor 21 (Fgf21) is produced by the heart and exerts protective effects, preventing cardiac hypertrophy development. The aim of the study was to determine the effects of Fgf21 during oxidative stress signalling in the heart. METHODS AND RESULTS: Fgf21 treatment in cardiomyocytes in culture induced the expression of genes encoding proteins involved in antioxidative pathways, including mitochondrial uncoupling proteins (Ucp2 and Ucp3) and superoxide dismutase-2 (Sod2) and reduced ROS production. In keeping with this, expression of antioxidant genes in response to lipopolysaccharide (LPS)-induced stimulation of pro-inflammatory pathways or isoproterenol-induced cardiac hypertrophy in the heart was reduced in Fgf21-null mice. Moreover, we found that Fgf21 is expressed in and released by cardiomyocytes in response to LPS, and its expression is under the control of the Sirt1 (sirtuin-1) pathway. This Fgf21 released by cardiomyocytes acts in an autocrine manner to protect cells against oxidative stress. Finally, failing human hearts showed up-regulation of Fgf21, Ucp3, and Sod2, confirming the association between Fgf21 induction and the control of cardiac oxidative stress pathways. CONCLUSION: Our data indicate that Fgf21 regulates genes involved in antioxidant pathways in an autocrine manner, thus preventing ROS production in cardiac cells. Therefore, Fgf21 acts as an antioxidant factor in the heart, preventing induction of pro-oxidative pathways by inflammatory or hypertrophic conditions.


Assuntos
Comunicação Autócrina/fisiologia , Fatores de Crescimento de Fibroblastos/fisiologia , Insuficiência Cardíaca/prevenção & controle , Insuficiência Cardíaca/fisiopatologia , Coração/fisiologia , Estresse Oxidativo/fisiologia , Animais , Comunicação Autócrina/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Fatores de Crescimento de Fibroblastos/deficiência , Fatores de Crescimento de Fibroblastos/farmacologia , Coração/efeitos dos fármacos , Insuficiência Cardíaca/metabolismo , Humanos , Canais Iônicos/fisiologia , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Camundongos Knockout , Proteínas Mitocondriais/fisiologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/fisiologia , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/fisiologia , Proteína Desacopladora 2 , Proteína Desacopladora 3
13.
J Rheumatol ; 42(2): 222-7, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25399393

RESUMO

OBJECTIVE: To determine whether there is an association between different capillaroscopic findings and pulmonary function tests in systemic sclerosis (SSc). METHODS: We did a retrospective observational study in a cohort of patients with SSc and early SSc. Patients with at least 1 nailfold videocapillaroscopy (NVC) magnified 120× were included. Pathological findings were giant capillaries, angiogenesis, and density loss. Findings were compared with lung function values: percent expected value of forced vital capacity (FVC), DLCO, and FVC/DLCO ratio. Other variables collected were sex and SSc type, and the presence of digital ulcers (DU), interstitial lung disease (ILD), scleroderma renal crisis, and/or pulmonary hypertension (PH). RESULTS: Of 136 patients with SSc, 85 had undergone an NVC. The frequency of ILD, DU, and PH was 24.1%, 28.7%, and 17.2%, respectively. Data analysis showed that patients with density loss had worse FVC% (86.91 ± 19.42 vs 101.13 ± 16.06, p < 0.01) and DLCO% (71.43 ± 21.19 vs 85.9 ± 19.81, p < 0.01) compared to those without. CONCLUSION: Patients with loss of density present worse FVC and DLCO values. Prospective studies are warranted to determine whether NVC is useful for studying pulmonary function in SSc.


Assuntos
Pulmão/fisiopatologia , Unhas/irrigação sanguínea , Fluxo Sanguíneo Regional/fisiologia , Escleroderma Sistêmico/fisiopatologia , Adulto , Idoso , Feminino , Humanos , Masculino , Angioscopia Microscópica , Pessoa de Meia-Idade , Testes de Função Respiratória , Estudos Retrospectivos
14.
Rev. esp. cardiol. (Ed. impr.) ; 67(10): 837-843, oct. 2014. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-128288

RESUMO

Introducción y objetivos El objetivo es determinar la frecuencia de uso y la disponibilidad en función del tiempo de las citas electrónicas recogidas en Revista Española de Cardiología y otras tres revistas biomédicas españolas, así como los factores que pueden influir en la disponibilidad y la recuperabilidad de los enlaces. Métodos Estudio descriptivo transversal que incluyó todas las citas de los trabajos publicados en el primer número del año de las revistas seleccionadas en los años pares desde 2002 hasta 2012. Se recogieron datos de revista, publicación, citas y enlaces. Las variables resultado fueron: porcentaje de artículos con al menos una cita electrónica, porcentaje de cita electrónica respecto al total de citas y porcentaje de accesibilidad y recuperabilidad de los enlaces. Resultados Se incluyeron 377 trabajos, de los que 73 (19,4%; intervalo de confianza (..) (AU)


Introduction and objectives We aimed to determine the frequency of use and accessibility over time of electronic citations in Revista Española de Cardiología and 3 other Spanish biomedical journals, and to identify the factors that influence the accessibility and retrievability of these links. Methods A cross-sectional, descriptive study was performed of all the references in articles published in the first issue of each even year from 2002 to 2012 in selected journals. Data were collected on the journal, publication, references, and links. The variables analyzed were the percentage of articles with at least 1 electronic citation, the percentage of electronic citations with respect to the total number of citations in the full sample, and the percentages of link accessibility and retrievability. Results We included 377 articles, of which 73 (19.4%; 95% confidence (..) (AU)


Assuntos
Humanos , Publicação Periódica , Fator de Impacto de Revistas , Bibliometria , Publicações Periódicas como Assunto/tendências , Bases de Dados de Citações , Políticas Editoriais
15.
Mitochondrion ; 18: 34-40, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25240745

RESUMO

Identifying genes that regulate mitochondrial DNA (mtDNA) levels is of interest due to an increasing number of diseases in humans that are associated with altered mtDNA levels. We searched for nuclear polymorphisms that influence mtDNA levels using a family-based genome-wide association (GWAS) method. Also, our aim was to determine if sex influences the genetic control of mtDNA levels. Two intron-polymorphisms, in the genes PARK2 and MRPL37, showed a tendency toward an association with mtDNA levels only in females and only in males, respectively. Both genes have a role in mitochondrial biogenesis and are potential candidates for the sex-specific control of mtDNA levels.


Assuntos
DNA Mitocondrial/biossíntese , Regulação da Expressão Gênica , Predisposição Genética para Doença , Trombofilia/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Estudo de Associação Genômica Ampla , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Proteínas Mitocondriais/genética , Polimorfismo Genético , Proteínas Ribossômicas/genética , Fatores Sexuais , Ubiquitina-Proteína Ligases/genética , Adulto Jovem
16.
Rev Esp Cardiol (Engl Ed) ; 67(10): 837-43, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25262130

RESUMO

INTRODUCTION AND OBJECTIVES: We aimed to determine the frequency of use and accessibility over time of electronic citations in Revista Española de Cardiología and 3 other Spanish biomedical journals, and to identify the factors that influence the accessibility and retrievability of these links. METHODS: A cross-sectional, descriptive study was performed of all the references in articles published in the first issue of each even year from 2002 to 2012 in selected journals. Data were collected on the journal, publication, references, and links. The variables analyzed were the percentage of articles with at least 1 electronic citation, the percentage of electronic citations with respect to the total number of citations in the full sample, and the percentages of link accessibility and retrievability. RESULTS: We included 377 articles, of which 73 (19.4%; 95% confidence interval, 15.2%-23.5%) had at least 1 electronic citation, and a total of 7077 references, of which 164 (2.3%; 95% confidence interval, 2.0%-2.7%) were electronic citations. Revista Española de Cardiología had 17 (15.2%) and 38 (1.3%), respectively. Use of electronic citations significantly increased over time (linear tendency, P < .001); 58 (35.4%; 95% confidence interval, 27.7%-43.0%), links were accessible, and information was retrieved in 55 cases (51.9%; 95% confidence interval, 41.9%-61.9%). Accessibility significantly decreased over time (linear tendency, P < .001); 45 electronic citations (27.5%; 95% confidence interval, 20.3%-34.6%) had complete additional information. Retrievability was significantly associated with the amount of additional information (linear tendency, P < .001). CONCLUSIONS: Electronic citations are increasingly used in some Spanish biomedical journals. Access to electronic citations is lost over time, and the probability of its retrieval is associated with the existence of additional information.


Assuntos
Bibliometria , Publicações Periódicas como Assunto/estatística & dados numéricos , Editoração/estatística & dados numéricos , Acesso à Informação , Estudos Transversais , Internet/estatística & dados numéricos , Espanha , Fatores de Tempo
17.
Pharmacogenomics ; 15(8): 1079-90, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25084201

RESUMO

BACKGROUND: Methotrexate (MTX) is the first-line treatment option for newly diagnosed rheumatoid arthritis (RA) patients. However, 50-70% of the patients respond to treatment and 30% suffer toxicity. AIM: To identify pharmacogenetic markers of outcome in RA patients treated with MTX. PATIENTS & METHODS: We analyzed 27 genetic variants in DHFR, TYMS, MTHFR, ATIC and CCND1 genes. RESULTS: We included 124 RA patients treated with MTX monotherapy. In multivariate analyses two variants in the MTHFR gene were associated with response, rs17421511 (p = 0.024) and rs1476413 (p = 0.0086), as well as one in the DHFR gene, rs1643650 (p = 0.026). The ATIC rs16853826 variant was associated with toxicity (p = 0.039). CONCLUSION: MTHFR, DHFR and ATIC genetic variants can be considered as pharmacogenetic markers of outcome in RA patients under MTX monotherapy.


Assuntos
Artrite Reumatoide/genética , Hidroximetil e Formil Transferases/genética , Metotrexato/administração & dosagem , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Complexos Multienzimáticos/genética , Nucleotídeo Desaminases/genética , Tetra-Hidrofolato Desidrogenase/genética , Adulto , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/patologia , Biomarcadores Farmacológicos , Ciclina D1/genética , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/classificação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Resultado do Tratamento
18.
Arthritis Res Ther ; 16(4): R153, 2014 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-25037855

RESUMO

INTRODUCTION: Adalimumab is a fully human anti-tumor necrosis factor α (anti-TNFα) monoclonal antibody that specifically blocks the interaction of TNFα with its receptors. It binds both soluble and transmembrane TNFα. We hypothesized that blocking these TNFα signals regulates the altered TNFα production in rheumatoid arthritis (RA) patients. METHODS: We compared, by flow cytometry, Toll-like receptor induction levels of membrane and intracellular TNFα in monocytes (iTNFα + CD14+ cells) from 12 patients before and after adalimumab treatment with those from 5 healthy donors. RESULTS: Before starting the treatment, the percentage of iTNFα+ CD14+ cells in the RA patients was significantly lower than that in healthy donors (mean ± SEM = 33.16 ± 4.82% vs 66.51 ± 2.4%, P < 0.001). When we added in vitro TNFα to healthy donor culture cells, levels of iTNFα+ CD14+ cells decreased, suggesting that the TNFα signal was responsible for the iTNFα+ CD14+ cell downregulation observed in the RA patients. After 2, 6 and 12 adalimumab injections, we observed significant blocking of membrane and soluble TNFα and a progressive increase in iTNFα+ CD14+ cells in ten patients with a good to moderate response as defined by the European League Against Rheumatism (EULAR) criteria. Levels of iTNFα+ CD14+ cells after 12 injections in these 10 patients were comparable to levels in healthy donors. In two patients, iTNFα+ CD14+ cell upregulation was not observed, and their EULAR-defined responses had not improved. The first patient developed antiadalimumab antibodies, explaining why adalimumab was not able to block membrane and soluble TNFα. In the second patient, adalimumab was discontinued because of adverse effects, which led to a decrease in iTNFα+ CD14+ cells to levels measured before treatment. CONCLUSIONS: Our findings suggest that adalimumab treatment in RA patients can return iTNFα levels to those of healthy donors. This effect was not observed in the presence of neutralizing antiadalimumab antibodies.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/imunologia , Fator de Necrose Tumoral alfa/biossíntese , Adalimumab , Artrite Reumatoide/metabolismo , Membrana Celular/metabolismo , Citoplasma/metabolismo , Feminino , Citometria de Fluxo , Humanos , Espaço Intracelular/metabolismo , Masculino , Pessoa de Meia-Idade , Monócitos/metabolismo
19.
Drugs Aging ; 31(7): 541-6, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24825616

RESUMO

BACKGROUND AND OBJECTIVES: Drug therapy in patients with advanced heart failure and limited life expectancy may be of no benefit or even inappropriate. The aim of this study was to analyze the appropriateness of medication prescribed to patients with advanced heart failure and limited life expectancy, considering as such an expected median survival of less than 6 months. METHODS: We retrospectively reviewed data on all patients with advanced heart failure who met criteria for limited life expectancy and who died in the geriatric ward of a tertiary hospital over a four-and-a-half-year period. We analyzed treatments prescribed before admission, especially drugs used for prophylaxis or to prolong life. RESULTS: A total of 72 patients were included. The mean age was 85.4 years, and 52.3 % were women. Mean Charlson index was 3.2. Prophylactic medications taken by patients at admission were antiplatelets in 40 patients (55.6 %), oral anticoagulants in 17 (23.6 %), statins in 14 (19.4 %), and osteoporosis medication in nine (12.5 %). Medications taken to prolong survival were angiotensin converting enzyme inhibitors or angiotensin II receptor antagonists in 29 patients (40.3 %). Other medications were iron supplements in 19 patients (26.4 %), vitamins in two (2.8 %), and acetylcholinesterase inhibitors in two (2.8 %). CONCLUSIONS: Our results show that patients with advanced heart failure and limited life expectancy were receiving an excessive number of prophylactic medications, drugs to prolong life, and other inappropriate treatments. These findings emphasize the need to review drug therapy in an individualized manner in elderly patients with advanced stages of heart disease and a poor prognosis.


Assuntos
Revisão de Uso de Medicamentos , Insuficiência Cardíaca/tratamento farmacológico , Hospitalização/estatística & dados numéricos , Expectativa de Vida , Idoso , Idoso de 80 Anos ou mais , Feminino , Insuficiência Cardíaca/mortalidade , Humanos , Masculino
20.
Calcif Tissue Int ; 94(6): 590-6, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24687525

RESUMO

There is evidence for a genetic contribution to bone mineral density (BMD×). Different loci affecting BMD have been identified by diverse linkage and genome-wide association studies. We studied the heritability of and the correlations among six densitometric phenotypes and four bone mass/fracture phenotypes. For this purpose, we used a family-based study of the genetics of osteoporosis, the Genetic Analysis of Osteoporosis Project. The primary aim of our study was to examine the roles of genetic and environmental factors in determining osteoporosis-related phenotypes. The project consisted of 11 extended families from Spain. All of them were selected through a proband with osteoporosis. BMD was measured using dual-energy X-ray absorptiometry. The proportion of variance of BMD attributable to significant covariates ranged from 25% (for femoral neck BMD) to 48% (for whole-body total BMD). The vast majority of the densitometric phenotypes had highly significant heritability, ranging from 0.252 (whole-body total BMD) to 0.537 (trochanteric BMD) after correcting for covariate effects. All of the densitometric phenotypes showed high and significant genetic correlations (from -0.772 to -1.000) with a low bone mass/osteopenia condition (Affected 3). Our findings provide additional evidence on the heritability of BMD and a strong genetic correlation between BMD and bone mass/fracture phenotypes in a Spanish population. Our results emphasize the importance of detecting genetic risk factors and the benefit of early diagnosis and especially therapeutic and preventive strategies.


Assuntos
Densidade Óssea/genética , Predisposição Genética para Doença , Osteoporose/genética , Absorciometria de Fóton , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Família , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo , Espanha , Adulto Jovem
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