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1.
Rheumatol Int ; 40(11): 1857-1864, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32200425

RESUMO

There is a high percentage of error in the approach of patients with joint pain by primary care physicians. An algorithm can help improve this misdiagnosis problem. Our study seeks to determine the effectiveness of an algorithm when used by primary care physicians for the diagnosis of cases of joint pain patients. A randomized clinical experiment was carried out. Primary care physicians from five cities in Colombia developed a series of clinical cases, which were presented to them through a website on their personal cell phones. Half of the doctors developed the cases using the diagnostic algorithm, and the other half developed the cases without the use of the algorithm. Main measures were proportion of correct diagnosis, number, type of laboratory and diagnostic images requested for the diagnostic approach of clinical cases. Two hundred and twenty-four primary care physicians participated. The overall proportion of cases correctly diagnosed was 37.3% higher in the intervention group; we found a greater difference in cases of spondyloarthritis (60.8%), followed by systemic lupus erythematosus with joint involvement (32.2%), rheumatoid arthritis (30.3%) and osteoarthritis (25.9%). The average number of tests requested to develop clinical cases was lower in the intervention group than in the control group, both globally and for each of the four diseases, with statistically significant differences for each of the comparisons. The diagnostic algorithm proved to be an effective tool when used by primary care physicians; the proportion of correct diagnoses increased, and the number of tests requested in the development of the cases decreased.


Assuntos
Algoritmos , Artralgia/diagnóstico , Artrite Reumatoide/diagnóstico , Erros de Diagnóstico/prevenção & controle , Lúpus Eritematoso Sistêmico/diagnóstico , Osteoartrite/diagnóstico , Médicos de Atenção Primária , Espondiloartropatias/diagnóstico , Adulto , Artralgia/etiologia , Artrite Reumatoide/complicações , Colômbia , Feminino , Humanos , Lúpus Eritematoso Sistêmico/complicações , Masculino , Pessoa de Meia-Idade , Osteoartrite/complicações , Distribuição Aleatória , Espondiloartropatias/complicações
2.
Lupus ; 28(9): 1167-1173, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31299882

RESUMO

Management of systemic lupus erythematosus patients is challenging because of disease heterogeneity. Although treatment of renal nephritis is more standardized, treating non-renal lupus activity remains controversial. Our objective was to identify non-renal, non-neurologic persistent active systemic lupus erythematosus patients in our cohort and described therapeutic behaviors in them. All systemic lupus erythematosus patients (American College of Rheumatology and/or Systemic Lupus Erythematosus International Collaborating Clinics criteria) seen at a university hospital between 2000 and 2017 were included and electronic medical records manually reviewed. Persistent lupus activity was defined as a patient with a Systemic Lupus Erythematosus Disease Activity Index score ≥ 6 (without renal and central nervous system manifestations) despite being on a stable treatment regimen for ≥ 30 days. Stable treatment could include prednisone alone (7.5-40 mg/d) or combined with antimalarial drugs and immunosuppressant therapies. A total of 257 lupus patients were included, 230 females (89.5%, 95% confidence interval 85.1-92.7), mean age at diagnosis 29.9 years (SD 16.4). After a median cohort follow-up of 5.7 years (interquartile range 2.4-10.2), 14 patients (5.4%, 95% confidence interval 3.2-9.0) showed persistent non-renal non neurologic lupus activity, with a median disease duration of 11.3 years (interquartile range 3.6-19.4). At that time, 12/14 (85.7 %, 95% confidence interval 52.6-97.0%) had low complement and 11/14 (78.6 %, 95% confidence interval 46.5-93.9%) had positive antiDNA antibodies. The main reasons for being refractory were mucocutaneous disease (50%, 95% confidence interval 23.5-76.5) and arthritis (42.9%, 95% confidence interval 18.5-71.2). Therapeutic choices after being refractory were: only increasing corticosteroid dose in one patient, starting rituximab in four, belimumab in eight, and in one mycophenolate and rituximab; with good response in all of them. In conclusion, 5.4% of systemic lupus erythematosus patients in our cohort were considered to have non-renal non neurologic persistent lupus activity, with mucocutaneous and arthritis the main manifestations. In total, 92.8% of these patients started a biologic treatment at this point (rituximab or belimumab).


Assuntos
Glucocorticoides/administração & dosagem , Imunossupressores/administração & dosagem , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Adolescente , Adulto , Anticorpos Monoclonais Humanizados/administração & dosagem , Antimaláricos/administração & dosagem , Argentina , Estudos de Coortes , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Prednisona/administração & dosagem , Estudos Retrospectivos , Rituximab/administração & dosagem , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
3.
Qual Life Res ; 28(1): 187-197, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30317425

RESUMO

OBJECTIVES: Outcomes obtained using different physical function patient reported outcome measures (PROMs) are difficult to compare. To facilitate standardization of physical function outcome measurement and reporting we developed an item response theory (IRT) based standardized physical function score metric for ten commonly used physical function PROMs. METHODS: Data of a total of 16,386 respondents from representative cohorts of patients with rheumatic diseases as well as the Dutch general population were used to map the items of ten commonly used physical function PROMs on a continuous latent physical function variable. The resulting IRT based common metric was cross-validated in an independent dataset of 243 patients with gout, osteoarthritis or polymyalgia in which four of the linked PROMs were administered. RESULTS: Our analyses supported that all 97 items of the ten included PROMs relate to a single underlying physical function variable and that responses to each item could be described by the generalized partial credit IRT model. In the cross-validation analyses we found congruent mean scores for four different PROMs when the IRT based scoring procedures were used. CONCLUSIONS: We showed that the standardized physical function score metric developed in this study can be used to facilitate standardized reporting of physical function outcomes for ten commonly used make physical function PROMs.


Assuntos
Avaliação de Resultados em Cuidados de Saúde/métodos , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida/psicologia , Etnicidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite , Projetos de Pesquisa , Doenças Reumáticas , Inquéritos e Questionários
4.
Mol Psychiatry ; 22(7): 961-971, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-27843148

RESUMO

Overconsumption of high-fat diets (HFDs) can critically affect synaptic and cognitive functions within telencephalic structures such as the medial prefrontal cortex (mPFC). The underlying mechanisms, however, remain largely unknown. Here we show that adolescence is a sensitive period for the emergence of prefrontal cognitive deficits in response to HFD. We establish that the synaptic modulator reelin (RELN) is a critical mediator of this vulnerability because (1) periadolescent HFD (pHFD) selectively downregulates prefrontal RELN+ cells and (2) augmenting mPFC RELN levels using transgenesis or prefrontal pharmacology prevents the pHFD-induced prefrontal cognitive deficits. We further identify N-methyl-d-aspartate-dependent long-term depression (NMDA-LTD) at prefrontal excitatory synapses as a synaptic signature of this association because pHFD abolishes NMDA-LTD, a function that is restored by RELN overexpression. We believe this study provides the first mechanistic insight into the vulnerability of the adolescent mPFC towards nutritional stress, such as HFDs. Our findings have primary relevance to obese individuals who are at an increased risk of developing neurological cognitive comorbidities, and may extend to multiple neuropsychiatric and neurological disorders in which RELN deficiency is a common feature.


Assuntos
Moléculas de Adesão Celular Neuronais/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Córtex Pré-Frontal/crescimento & desenvolvimento , Córtex Pré-Frontal/metabolismo , Serina Endopeptidases/metabolismo , Animais , Dieta Hiperlipídica/efeitos adversos , Masculino , Desnutrição/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Plasticidade Neuronal , Receptores de N-Metil-D-Aspartato/metabolismo , Proteína Reelina , Sinapses/metabolismo
5.
Lupus ; 26(1): 73-83, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27230554

RESUMO

OBJECTIVES: The objective of this study was to examine whether early discoid lupus erythematosus (DLE) would be a protective factor for further lupus nephritis in patients with systemic lupus erythematosus (SLE). METHODS: We studied SLE patients from GLADEL, an inception longitudinal cohort from nine Latin American countries. The main predictor was DLE onset, which was defined as physician-documented DLE at SLE diagnosis. The outcome was time from the diagnosis of SLE to new lupus nephritis. Univariate and multivariate survival analyses were conducted to examine the association of DLE onset with time to lupus nephritis. RESULTS: Among 845 GLADEL patients, 204 (24.1%) developed lupus nephritis after SLE diagnosis. Of them, 10 (4.9%) had DLE onset, compared to 83 (12.9%) in the group of 641 patients that remained free of lupus nephritis (hazard ratio 0.39; P = 0.0033). The cumulative proportion of lupus nephritis at 1 and 5 years since SLE diagnosis was 6% and 14%, respectively, in the DLE onset group, compared to 14% and 29% in those without DLE (P = 0.0023). DLE onset was independently associated with a lower risk of lupus nephritis, after controlling for sociodemographic factors and disease severity at diagnosis (hazard ratio 0.38; 95% confidence interval 0.20-0.71). CONCLUSIONS: Our data indicate that DLE onset reduces the risk of further lupus nephritis in patients with SLE, independently of other factors such as age, ethnicity, disease activity, and organ damage. These findings have relevant prognosis implications for SLE patients and their clinicians. Further studies are warranted to unravel the biological and environmental pathways associated with the protective role of DLE against renal disease in patients with SLE.


Assuntos
Lúpus Eritematoso Discoide/epidemiologia , Lúpus Eritematoso Sistêmico/epidemiologia , Nefrite Lúpica/epidemiologia , Adolescente , Adulto , Estudos de Coortes , Feminino , Humanos , América Latina/epidemiologia , Estudos Longitudinais , Lúpus Eritematoso Discoide/fisiopatologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Prognóstico , Fatores de Proteção , Índice de Gravidade de Doença , Análise de Sobrevida , Fatores de Tempo , Adulto Jovem
6.
Scand J Rheumatol ; 46(1): 17-21, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27095187

RESUMO

OBJECTIVES: To evaluate the association between learned helplessness (LH) and self-efficacy (SE) with disease activity, functional capacity, and level of pain in patients with rheumatoid arthritis (RA) and to compare LH and SE between patients in remission and patients with active disease. METHOD: This multicentre, cross-sectional study included consecutive patients (aged ≥ 18 years) with RA according to 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria. LH was measured by the Rheumatology Attitude Index (RAI), Spanish version; SE with the Arthritis Self-efficacy Scale (ASES), Spanish version; functional capacity with the Health Assessment Questionnaire, Argentinian version (HAQ-A); and perceived pain by the visual analogue scale (VAS). Disease activity was measured by the Clinical Disease Activity Index (CDAI). RESULTS: A total of 115 patients (82% females) with a mean (± sd) age of 58 ± 13 years were included. We found a significantly positive correlation between LH and perceived pain (p < 0.001), HAQ-A score (p < 0.001), and CDAI (p < 0.001) and a significantly negative correlation between SE and perceived pain (p < 0.001), HAQ-A score (p < 0.001), and CDAI (p < 0.001). We found greater levels of SE and lower grades of LH in patients in remission compared to those with active disease (median 76 vs. 58; p < 0.001 and 6 vs. 11; p < 0.001, respectively). CONCLUSIONS: LH and SE correlated significantly with disease activity, functional capacity, and perceived pain. Levels of SE were higher in patients in remission compared to those with active disease as opposed to levels of LH, which were lower in patients in remission compared to those with active disease. These results show that cognitive factors are related to disease activity and their modifications may have importance in the management of RA.


Assuntos
Artrite Reumatoide/psicologia , Desamparo Aprendido , Percepção da Dor , Autoeficácia , Idoso , Argentina , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença
7.
Genet Mol Res ; 16(2)2017 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-28453177

RESUMO

The use of Y chromosome haplotypes, important for the detection of sexual crimes in forensics, has gained prominence with the use of databases that incorporate these genetic profiles in their system. Here, we optimized and validated an amplification protocol for Y chromosome profile retrieval in reference samples using lesser materials than those in commercial kits. FTA® cards (Flinders Technology Associates) were used to support the oral cells of male individuals, which were amplified directly using the SwabSolution reagent (Promega). First, we optimized and validated the process to define the volume and cycling conditions. Three reference samples and nineteen 1.2 mm-diameter perforated discs were used per sample. Amplification of one or two discs (samples) with the PowerPlex® Y23 kit (Promega) was performed using 25, 26, and 27 thermal cycles. Twenty percent, 32%, and 100% reagent volumes, one disc, and 26 cycles were used for the control per sample. Thereafter, all samples (N = 270) were amplified using 27 cycles, one disc, and 32% reagents (optimized conditions). Data was analyzed using a study of equilibrium values between fluorophore colors. In the samples analyzed with 20% volume, an imbalance was observed in peak heights, both inside and in-between each dye. In samples amplified with 32% reagents, the values obtained for the intra-color and inter-color standard balance calculations for verification of the quality of the analyzed peaks were similar to those of samples amplified with 100% of the recommended volume. The quality of the profiles obtained with 32% reagents was suitable for insertion into databases.


Assuntos
Cromossomos Humanos Y/genética , Genética Forense/métodos , Haplótipos , Reação em Cadeia da Polimerase/métodos , Bases de Dados de Ácidos Nucleicos , Humanos , Masculino , Repetições de Microssatélites
8.
Lupus ; 24(8): 788-95, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25504653

RESUMO

OBJECTIVE: To examine the characteristics of patients who developed late onset systemic lupus erythematosus (SLE) in the GLADEL (Grupo Latino Americano de Estudio del Lupus) cohort of patients with SLE. METHODS: Patients with SLE of less than two years of disease duration, seen at 34 centers of nine Latin American countries, were included. Late-onset was defined as >50 years of age at time of first SLE-related symptom. Clinical and laboratory manifestations, activity index (SLEDAI), and damage index (SLICC/ACR- DI) were ascertained at time of entry and during the course (cumulative incidence). Features were compared between the two patient groups (<50 and ≥50) using descriptive statistics and hypothesis tests. Logistic regression was performed to examine the association of late-onset lupus, adjusting for other variables. RESULTS: Of the 1480 patients included, 102 patients (6.9 %) had late-onset SLE, 87% of which were female. Patients with late-onset SLE had a shorter follow-up (3.6 vs. 4.4 years, p < 0.002) and a longer time to diagnosis (10.1 vs. 5.8 months, p < 0.001) compared to the younger onset group. Malar rash, photosensitivity, and renal involvement were less prevalent while interstitial lung disease, pleural effusions, and sicca symptoms were more frequent in the older age group (p > 0.05). In multivariable analysis, late onset was independently associated with higher odds of ocular (OR = 3.66, 95% CI = 2.15-6.23), pulmonary (OR = 2.04, 95% CI = 1.01-4.11), and cardiovascular (OR = 1.76, 95% CI = 1.04-2.98) involvement and lower odds of cutaneous involvement (OR = 0.41, 95% CI = 0.21-0.80), number of cumulative SLE criteria (OR = 0.79, 95% CI = 0.64-0.97), use of cyclophosphamide (OR = 0.47, 95% CI = 0.24-0.95), and anti-RNP antibodies (OR = 0.43, 95% CI = 0.20-0.91). A Cox regression model revealed a higher risk of dying in older onset than the younger-onset SLE (OR = 2.61, 95% CI = 1.2-5.6). CONCLUSION: Late-onset SLE in Latin Americans had a distinct disease expression compared to the younger-onset group. The disease seems to be mild with lower cumulative SLE criteria, reduced renal/mucocutaneous involvements, and less use of cyclophosphamide. Nevertheless, these patients have a higher risk of death and of ocular, pulmonary, and cardiovascular involvements.


Assuntos
Ciclofosfamida/uso terapêutico , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/etnologia , Adolescente , Adulto , Idade de Início , Idoso , Feminino , Hispânico ou Latino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Índice de Gravidade de Doença , Adulto Jovem
9.
Mol Psychiatry ; 18(4): 451-60, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23399915

RESUMO

Adult hippocampal neurogenesis (AHN) is crucial for the maintenance of hippocampal function. Several neurodegenerative diseases such as Alzheimer's disease (AD) are accompanied by memory deficits that could be related to alterations in AHN. Here, we took advantage of a conditional mouse model to study the involvement of glycogen synthase kinase-3ß (GSK-3ß) overexpression (OE) in AHN. By injecting GFP- and PSD95-GFP-expressing retroviruses, we have determined that hippocampal GSK-3ß-OE causes dramatic alterations in both dendritic tree morphology and post-synaptic densities in newborn neurons. Alterations in previously damaged neurons were reverted by switching off the transgenic system and also by using a physiological approach (environmental enrichment) to increase hippocampal plasticity. Furthermore, comparative morphometric analysis of granule neurons from patients with AD and from GSK-3ß overexpressing mice revealed shared morphological alterations. Taken together, these data indicate that GSK-3ß is crucial for hippocampal function, thereby supporting this kinase as a relevant target for the treatment of AD.


Assuntos
Doença de Alzheimer/enzimologia , Doença de Alzheimer/fisiopatologia , Dendritos/ultraestrutura , Quinase 3 da Glicogênio Sintase/biossíntese , Hipocampo/anatomia & histologia , Neurogênese/fisiologia , Densidade Pós-Sináptica/ultraestrutura , Doença de Alzheimer/genética , Animais , Meio Ambiente , Quinase 3 da Glicogênio Sintase/genética , Glicogênio Sintase Quinase 3 beta , Hipocampo/enzimologia , Hipocampo/fisiologia , Humanos , Camundongos , Camundongos Transgênicos , Neurônios/citologia , Neurônios/fisiologia , Regulação para Cima
10.
Clin Exp Rheumatol ; 32(6 Suppl 86): S-94-7, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25198424

RESUMO

OBJECTIVES: Prevalence of systemic sclerosis (SSc) and different clinical subsets varies across the world. Few data have been published on SSc patients in Latin America. Our objective was to describe a SSc cohort in Argentina and to compare clinical findings, disease subsets and antibodies with other international SSc populations. METHODS: Patients with SSc (n=234) seen at the Rheumatology section of the Hospital Italiano de Buenos Aires between 2000-2011 were retrospectively analysed. Data on clinical manifestations, disease subsets and antibodies were obtained. Patients were classified into diffuse cutaneous (dc) and limited cutaneous (lc) subsets. Comparison with other cohorts (France, United States, Germany, Italy, Mexico, EUSTAR and Brazil) was made based on published information. RESULTS: A higher female:male ratio (12:1) and a higher limited subset prevalence (76.1%) was found in this Argentine cohort comparing with others. We also found a lower prevalence of diffuse disease, anti Scl-70 (antitopoisomerase) and nucleolar pattern antinuclear antibodies. Within each subset, clinical findings were similar with other SSc populations except for a very low prevalence in renal crisis (0.02% of dc SS). CONCLUSIONS: With slight variations perhaps due to genetic, environmental or referral factors, SSc in this cohort appears to be similar to that described in other parts of the world.


Assuntos
Esclerodermia Difusa/epidemiologia , Esclerodermia Limitada/epidemiologia , Adulto , Idoso , Anticorpos Antinucleares/imunologia , Argentina/epidemiologia , Autoanticorpos/imunologia , Brasil/epidemiologia , Estudos de Coortes , DNA Topoisomerases Tipo I , Feminino , França/epidemiologia , Gastroenteropatias/epidemiologia , Alemanha/epidemiologia , Humanos , Hipertensão Pulmonar/epidemiologia , Itália/epidemiologia , Doenças Pulmonares Intersticiais/epidemiologia , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Proteínas Nucleares/imunologia , Prevalência , Estudos Retrospectivos , Esclerodermia Difusa/imunologia , Esclerodermia Limitada/imunologia , Distribuição por Sexo , Estados Unidos/epidemiologia
11.
Neurologia (Engl Ed) ; 37(8): 647-652, 2022 Oct.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31899017

RESUMO

BACKGROUND: Advanced interatrial block (IAB) is an independent risk factor for ischaemic stroke. This study aimed to analyse whether advanced IAB predicts recurrence of embolic stroke of undetermined source (ESUS). METHODS: 104 patients with a confirmed diagnosis of ESUS were followed up for a median period of 15 months (interquartile range, 10-48). We recorded data on clinical variables, P-wave characteristics, and presence of IAB on the electrocardiogram. Electrocardiogram findings were interpreted by a blinded, centralised rater at (XXXX2). ESUS recurrence was the primary outcome variable. RESULTS: Median age was 47 years (range, 19-85); 50% of patients were women. IAB was detected in 36 patients (34.6%); IAB was partial in 29 cases (27.9%) and advanced in 7 (6.7%). Sixteen patients (15.4%) presented stroke recurrence; of these, 5 had partial and 4 had advanced IAB (P = .01; odds ratio [OR] = 9.44; 95% confidence interval [CI], 1.88-47.46; relative risk [RR] = 4.62; 95% CI, 2.01-10.61). Median P-wave duration was longer in patients with stroke recurrence (P = .009). The multivariate logistic regression analysis identified the following independent risk factors for stroke recurrence: advanced IAB (P < .001; OR = 10.86; 95% CI, 3.07-38.46), male sex (P = .028; OR = 4.6; 95% CI, 1.18-17.96), and age older than 50 years (P = .039; OR = 3.84; 95% CI, 1.06-13.88). In the Cox proportional hazards model, the risk variables identified were age older than 50 years (P = .002; hazard ratio, 7.04; 95% CI, 2.06-23.8) and P-wave duration (per ms) (P = .007; hazard ratio, 1.02; 95% CI, 1.01-1.04). CONCLUSIONS: Advanced IAB and age older than 50 years predict ESUS recurrence.

12.
Neurologia (Engl Ed) ; 37(8): 647-652, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34656503

RESUMO

BACKGROUND: Advanced interatrial block (IAB) is an independent risk factor for ischaemic stroke. This study aimed to analyse whether advanced IAB predicts recurrence of embolic stroke of undetermined source (ESUS). METHODS: 104 patients with a confirmed diagnosis of ESUS were followed up for a median period of 15 months (interquartile range, 10-48). We recorded data on clinical variables, P-wave characteristics, and presence of IAB on the electrocardiogram (ECG). ECG findings were interpreted by a blinded, centralised rater at (XXXX2). ESUS recurrence was the primary outcome variable. RESULTS: Median age was 47 years (range, 19-85); 50% of patients were women. IAB was detected in 36 patients (34.6%); IAB was partial in 29 cases (27.9%) and advanced in 7 (6.7%). Sixteen patients (15.4%) presented stroke recurrence; of these, 5 had partial and 4 had advanced IAB (P = .01; odds ratio [OR] = 9.44; 95% confidence interval [CI], 1.88-47.46; relative risk [RR] = 4.62; 95% CI, 2.01-10.61). Median P-wave duration was longer in patients with stroke recurrence (P = .009). The multivariate logistic regression analysis identified the following independent risk factors for stroke recurrence: advanced IAB (P < .001; OR = 10.86; 95% CI, 3.07-38.46), male sex (P = .028; OR = 4.6; 95% CI, 1.18-17.96), and age older than 50 years (P = .039; OR = 3.84; 95% CI, 1.06-13.88). In the Cox proportional hazards model, the risk variables identified were age older than 50 years (P = .002; hazard ratio, 7.04; 95% CI, 2.06-23.8) and P-wave duration (per ms) (P = .007; hazard ratio, 1.02; 95% CI, 1.01-1.04). CONCLUSIONS: Advanced IAB and age older than 50 years predict ESUS recurrence.


Assuntos
Fibrilação Atrial , Isquemia Encefálica , AVC Embólico , Acidente Vascular Cerebral , Fibrilação Atrial/diagnóstico , Isquemia Encefálica/diagnóstico , Feminino , Humanos , Bloqueio Interatrial/complicações , Bloqueio Interatrial/diagnóstico , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia
13.
Allergy ; 66(8): 999-1004, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21426358

RESUMO

Modification of the response to allergens at an early stage and thereby of the natural history of a respiratory allergic disease by preventing disease progression would constitute the key benefit of specific immunotherapy (SIT) in children. However, although allergen products for SIT have been on the market on a named-patient basis for many years, long-term efficacy, the optimal duration of the treatment and the optimal dosage have not been sufficiently elaborated until now. The enactment of the Therapy Allergen Ordinance in Germany mandates that allergen products for SIT of the most prevalent allergies must submit an application for marketing authorization to the German authorities. In line with the European Paediatric Regulation, decisions by the European Medicines Agency on agreed paediatric investigation plans must be included in these applications. These regulatory requirements provide a unique opportunity to fill the gap in knowledge concerning the benefits of SIT for children and to obtain the data needed to support evidence-based authorization of allergen products for immunotherapy. This goal can only be achieved through close cooperation between academia, drug regulators and industry as well as parent/patient organizations.


Assuntos
Alérgenos/uso terapêutico , Comportamento Cooperativo , Dessensibilização Imunológica/métodos , Controle de Medicamentos e Entorpecentes/métodos , Centros Médicos Acadêmicos , Criança , Descoberta de Drogas , Indústria Farmacêutica , Humanos
14.
Neurobiol Stress ; 14: 100303, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33614865

RESUMO

Females that experience chronic stress during development, particularly adolescence, are the most vulnerable group to stress-induced disease. While considerable attention has been devoted to stress-induced manifestation of anxiety, depression, and PTSD, evidence indicates that a history of chronic stress is also a risk factor for cognitive decline and dementia - with females again in a higher risk group. This interplay between sex and stress history indicates specific mechanisms drive neural dysfunction across the lifespan. The presence of sex and stress steroid receptors in the hippocampus provides a point of influence for these variables to drive changes in cognitive function. Here, we used a rodent model of chronic adolescent stress (CAS) to determine the extent to which CAS modifies glutamatergic signaling resulting in cognitive dysfunction. Male and female Wistar rats born in-house remained non-stressed (NS), unmanipulated aside from standard cage cleaning, or were exposed to either physical restraint (60 min) or social defeat (CAS) each day (6 trials each), along with social isolation, throughout the adolescent period (PND 35-47). Cognition was assessed in adult (PND 80-130) male and female rats (n = 10-12) using the Barnes Maze task and the Attention Set-Shift task. Whole hippocampi were extracted from a second cohort of male and female rats (NS and CAS; n = 9-10) and processed for RNA sequencing. Brain tissue from the first cohort (n = 6) was processed for density of glutamatergic synaptic markers (GluA1, NMDA1a, and synaptophysin) or whole-cell patch clamping (n = 4) to determine glutamatergic activity in the hippocampus. Females with a history of chronic stress had shorter latencies to locate the goal box than NS controls during acquisition learning but showed an increased latency to locate the new goal box during reversal learning. This reversal deficit persisted across domains as females with a history of stress required more trials to reach criterion during the reversal phases of the Attention Set-Shift task compared to controls. Ovariectomy resulted in greater performance variability overall during reversal learning with CAS females showing worse performance. Males showed no effects of CAS history on learning or memory performance. Bioinformatic prediction using gene ontology categorization indicated that in females, postsynaptic membrane gene clusters, specifically genes related to glutamatergic synapse remodeling, were enriched with a history of stress. Structural analysis indicated that CAS did not alter glutamate receptor density in females. However, functionally, CAS females had a decreased AMPA/NMDA-dependent current ratio compared to controls indicating a weakening in synaptic strength in the hippocampus. Males showed only a slight change in density of NMDA1a labeling in the CA3 region with a history of stress. The data observed here suggest that females are at risk for impaired cognitive flexibility following a history of adolescent stress, possibly driven by changes in glutamatergic signaling.

16.
Eur J Neurol ; 17(3): 479-82, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19922459

RESUMO

OBJECTIVE: The present study was undertaken to determine the incidence of MS in a health maintenance organization from Buenos Aires, the largest populated area in Argentina. METHODS: Population was all members of a hospital-based health maintenance organization who were affiliated since January 1992 up to December 2007. Each person was followed contributing time at risk since January 1992 or enrollment date to the final date. Patients with definite diagnosis according to Poser's criteria were included. Incidence density was calculated with 95% confidence intervals. RESULTS: A total of 145,000 patients were followed for a total of 1,021,515 person-years, of whom 18 developed the disease. Incidence density (ID): 1.76 /100 000 person-years (95% CI: 1.1-2.8/100,000 person-years). CONCLUSION: The incidence density of 1.76 per 100,000 suggests a low-median risk area for MS. This study constitutes the first of its kind to cover data of MS incidence in Argentina.


Assuntos
Esclerose Múltipla/epidemiologia , Adolescente , Adulto , Idade de Início , Idoso , Argentina/epidemiologia , Criança , Pré-Escolar , Etnicidade , Feminino , Humanos , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Fatores Socioeconômicos , Fatores de Tempo , Adulto Jovem
17.
Neotrop Entomol ; 49(2): 227-233, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31849022

RESUMO

Before a population becomes extinct, there are hidden costs in the physiology at the individual level that provide valuable insights into their condition. Here, we study two dams with one species in common (Argia anceps Garrison, 1996) to evaluate whether their physiological condition differed (total protein quantity, prophenoloxidase (proPO) and phenoloxidase (PO) activity, and protein carbonylation) during two consecutive years. The first dam, "El Gallinero" (contaminated, C), contains organic input from mines and agricultural activity, whereas the second, "Paso de Vaqueros" (non-contaminated, NC), is part of a biosphere reserve. Although at a phenological level, some physiological differences were observed (2012 vs 2013), individuals from the contaminated population had less total protein (2012, median = 1.815 µg/µL; 2013, 0.081 µg/µL) and more carbonylations in their proteins (2012, median = 19.00 nmol/mg; 2013, median = 121.69 nmol/mg) compared with the non-contaminated population (protein quantity in 2012, median = 3.716 µg/µL; 2013, median = 0.054 µg/µL; protein carbonylations in 2012, median = 0.00 nmol/mg; 2013, median = 99.44 nmol/mg). However, no significant differences were found in prophenoloxidase (C, median = 0.002 Vmax; NC, median = 0.002 Vmax) and phenoloxidase activity (C, median = 0.002 Vmax; NC, median = 0.001 Vmax). In addition, the biological oxygen demand (BOD) and Zn were more elevated in the C than NC population (C, BOD = 11.7, Zn = 0.17; NC, BOD = 8, Zn = 0.14). The results show that the impact of human activity can be observed not only through the extinction of species, but also at the physiological level of the individuals composing the populations through the evaluation of biomolecular damage, which can be observed at a much shorter scale compared with species extinction.


Assuntos
Poluição Ambiental/efeitos adversos , Odonatos/fisiologia , Animais , Organismos Aquáticos , Catecol Oxidase , Monitoramento Ambiental , Precursores Enzimáticos , Proteínas de Insetos , México , Monofenol Mono-Oxigenase , Carbonilação Proteica
18.
Ann Rheum Dis ; 68(9): 1387-94, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18952643

RESUMO

OBJECTIVE: To develop comprehensive recommendations for the treatment of the various clinical manifestations of psoriatic arthritis (PsA) based on evidence obtained from a systematic review of the literature and from consensus opinion. METHODS: Formal literature reviews of treatment for the most significant discrete clinical manifestations of PsA (skin and nails, peripheral arthritis, axial disease, dactylitis and enthesitis) were performed and published by members of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA). Treatment recommendations were drafted for each of the clinical manifestations by rheumatologists, dermatologists and PsA patients based on the literature reviews and consensus opinion. The level of agreement for the individual treatment recommendations among GRAPPA members was assessed with an online questionnaire. RESULTS: Treatment recommendations were developed for peripheral arthritis, axial disease, psoriasis, nail disease, dactylitis and enthesitis in the setting of PsA. In rotal, 19 recommendations were drafted, and over 80% agreement was obtained on 16 of them. In addition, a grid that factors disease severity into each of the different disease manifestations was developed to help the clinician with treatment decisions for the individual patient from an evidenced-based perspective. CONCLUSIONS: Treatment recommendations for the cardinal physical manifestations of PsA were developed based on a literature review and consensus between rheumatologists and dermatologists. In addition, a grid was established to assist in therapeutic reasoning and decision making for individual patients. It is anticipated that periodic updates will take place using this framework as new data become available.


Assuntos
Artrite Psoriásica/tratamento farmacológico , Adulto , Anti-Inflamatórios não Esteroides/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Psoriásica/diagnóstico , Medicina Baseada em Evidências/métodos , Glucocorticoides/uso terapêutico , Humanos , Masculino , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto Jovem
20.
Lupus ; 18(11): 1019-25, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19762406

RESUMO

The objective was to determine the prevalence of the metabolic syndrome (MS) in patients with systemic lupus erythematosus (SLE) in Argentina, to assess the factors associated to it, and to compare the results with a control group with non-inflammatory disorders. The study included 147 patients with SLE and 119 controls. MS was defined according to criteria by the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) Scientific Statement. Demographic characteristics, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI) were assessed as well as administration, maximum dose and cumulative dose of prednisone and hydroxychloroquine (HCQ). MS prevalence was 28.6% (CI 95%: 21.4-36.6) in patients with SLE and 16% in controls (P = 0.0019). Patients with SLE presented higher arterial hypertension frequency compared with controls (43 vs 25%, P = 0.007). When comparing lupus patients with MS (n = 41) and without MS (n = 106), no significant differences were observed regarding duration of the disease, SLEDAI or cumulative prednisone dose. Cumulative damage was associated independently with MS (OR 1.98; P = 0.021), whereas HCQ use was found to be protective (OR 0.13; P = 0.015). Patients with lupus presented higher MS prevalence than controls with non-inflammatory disorders, and occurrence of arterial hypertension was also higher. MS was associated with cumulative damage; the use of HCQ showed to be protective against presence of MS.


Assuntos
Lúpus Eritematoso Sistêmico/fisiopatologia , Síndrome Metabólica/epidemiologia , Adulto , Argentina/epidemiologia , Estudos Transversais , Feminino , Humanos , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Análise de Regressão
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