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BACKGROUND: Systemic sclerosis (SSc) is a rare chronic autoimmune disease with heterogeneous manifestations. In the last decade, several clinical trials have been conducted to evaluate new treatment options for SSc. The purpose of this work is to update the recommendations of the Brazilian Society of Rheumatology in light of the new evidence available for the pharmacological management of SSc. METHODS: A systematic review including randomized clinical trials (RCTs) for predefined questions that were elaborated according to the Patient/Population, Intervention, Comparison, and Outcomes (PICO) strategy was conducted. The rating of the available evidence was performed according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. To become a recommendation, at least 75% agreement of the voting panel was needed. RESULTS: Six recommendations were elaborated regarding the pharmacological treatment of Raynaud's phenomenon, the treatment (healing) and prevention of digital ulcers, skin involvement, interstitial lung disease (ILD) and gastrointestinal involvement in SSc patients based on results available from RCTs. New drugs, such as rituximab, were included as therapeutic options for skin involvement, and rituximab, tocilizumab and nintedanib were included as therapeutic options for ILD. Recommendations for the pharmacological treatment of scleroderma renal crisis and musculoskeletal involvement were elaborated based on the expert opinion of the voting panel, as no placebo-controlled RCTs were found. CONCLUSION: These guidelines updated and incorporated new treatment options for the management of SSc based on evidence from the literature and expert opinion regarding SSc, providing support for decision-making in clinical practice.
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Doença de Raynaud , Reumatologia , Escleroderma Sistêmico , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/tratamento farmacológico , Humanos , Brasil , Reumatologia/normas , Doença de Raynaud/tratamento farmacológico , Sociedades Médicas , Doenças Pulmonares Intersticiais/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Rituximab/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Úlcera Cutânea/etiologia , Antirreumáticos/uso terapêuticoRESUMO
Anti-synthetase syndrome (ASyS) is a rare systemic autoimmune myopathy characterized by the involvement of muscles, lungs, and joints, in addition to Raynaud's phenomenon, "mechanics' hand," and fever. Laboratory ASyS is defined by the positivity of anti-aminoacyl-tRNA synthetase autoantibodies, of which anti-Jo-1 is the most common. Herein, we reported an ASyS defined by an anti-Ha autoantibody, which has rarely been described in the literature. Moreover, to the best of our knowledge, we reported the first case of anti-Ha ASyS in Brazil.
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Objective: The incorporation of immunobiological agents for rheumatoid arthritis (RA) treatment at the Brazilian Unified Health System (SUS) represented a significant advance but had an important impact on the budget. As the current model of direct patient delivery had deficiencies, the CEDMAC model of assisted therapy was implemented to focus on rational use to minimize expenses and increase access. However, there is no data to compare the two models. Thus, this study aimed to compare the number of bottles effectively dispensed by the CEDMAC model to direct dispensing and assess its financial impact. Methods: Care of RA patients at CEDMAC in 2015, whose immunobiological drugs were provided by the Ministry of Health, were included. Drug and dose received, prescribed dose, the number of bottles, cancellations due to contraindication, and absences were recorded. As a comparison, the number of bottles that would be delivered by direct dispensing was estimated. The difference between the total number of bottles dispensed by the two systems and the financial impact of the purchase price in 2015 was calculated. Results: In 2015, CEDMAC provided 3,784 consultations for RA patients. The total number of bottles of immunobiological agents prescribed was 10,000 bottles, and 1,946 (19.5%) were not used for bottle optimization, contraindications, or absenteeism. Unused bottles reduced expenses by R$ 806,132.62. The expansion of the model to the entire SUS would reduce costs by R$ 121,110,388.27. Conclusion: The CEDMAC assisted therapy model considerably reduces the volume of dispensed bottles and can significantly reduce expenses in the supply of immunobiological agents for RA at SUS.
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Objetivo: A incorporação dos imunobiológicos para tratamento da artrite reumatoide (AR) no Sistema Único de Saúde (SUS) representou um avanço significativo, porém teve um impacto importante no orçamento. Como o modelo vigente de dispensação direta ao paciente apresentava deficiências, implementou-se o modelo do CEDMAC de terapia assistida com foco no uso racional, visando minimizar despesas e potencializar o alcance. Entretanto, não há dados que comparem os dois modelos. Assim, esse estudo objetivou comparar o número de frascos efetivamente dispensados pelo modelo do CEDMAC à dispensação direta e avaliar seu impacto financeiro. Métodos: Foram incluídos atendimentos de pacientes com AR no CEDMAC em 2015, cujo imunobiológico foi fornecido pelo Ministério da Saúde. Foram registrados medicamento e dose recebidos, dose prescrita, número de frascos, cancelamentos por contraindicação e faltas. Como comparação, foi estimado o número de frascos que seriam entregues pela dispensação direta. Calculou-se a diferença entre o número total de frascos dispensados pelos dois sistemas e o impacto financeiro pelo valor de aquisição em 2015. Resultados: Em 2015, o CEDMAC realizou 3.784 atendimentos para pacientes com AR. O total de frascos de imunobiológicos prescritos foi de 10.000 frascos e 1.946 (19,5%) não foram utilizados por otimização de frascos, contraindicações ou absenteísmo. Os frascos não utilizados reduziram as despesas em R$ 806.132,62. A expansão do modelo para todo SUS reduziria as despesas em R$ 121.110.388,27. Conclusão: O modelo de terapia assistida do CEDMAC reduz consideravelmente o volume de frascos dispensados e pode trazer uma relevante redução de despesas no fornecimento dos imunobiológicos para AR no SUS.
Objective: The incorporation of immunobiologicals for the treatment of rheumatoid arthritis (RA) in the Brazilian Unified Health System (SUS) represented a significant advance but had an important impact on the budget. As the current model of direct delivery to the patient presented deficiencies, the CEDMAC model of assisted therapy focusing on rational use was implemented to minimize expenses and increase access. However, there is no data comparing the two models. Thus, this study aimed to compare the number of vials effectively dispensed by the CEDMAC model compared to direct delivery and to evaluate its financial impact. Methods: We included RA patients attended at CEDMAC during 2015, whose immunobiological was provided by Ministry of Health. Drug and dose received, prescribed dose, number of vials, cancellations due to contraindication and absences were recorded. As comparison, the number of vials that would be delivered by the direct delivery model were estimated. Savings were calculated by the difference between the total number of vials dispensed by the two systems and the financial impact by acquisition value in 2015. Results: During 2015, CEDMAC performed 3,784 consultations for RA patients. The total number of immunobiological vials prescribed was 10,000 vials and 1,946 (19.5%) were not used for vial optimization, contraindications or absenteeism. Saved vials reduced expenses by R$ 806,132.62. The expansion of the model for all SUS would reduce expenses by R$ 121,110,388.27. Conclusion: CEDMAC's model of assisted therapy considerably reduces the volume of dispensed vials and can bring significant cost offsets in the supply of RA immunobiologicals by SUS.
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Artrite Reumatoide , Custos e Análise de Custo , Uso de Medicamentos , Economia e Organizações de SaúdeRESUMO
Abstract Objective Therapeutic targets in Idiopathic Inflammatory Myopathies (IIM) are based on the opinions of physicians/specialists, which may not reflect the main concerns of patients. The authors, therefore, assessed the outcome concerns of patients with IIM and compared them with the concerns of rheumatologists in order to develop an IIM outcome standard set. Methods Ninety-three IIM patients, 51 rheumatologists, and one physiotherapist were invited to participate. An open questionnaire was initially applied. The top 10 answers were selected and applied in a multiple-choice questionnaire, inquiring about the top 3 major concerns. Answers were compared, and the agreement rate was calculated. Concerns were gathered in an IIM outcome standard set with validated measures. Results The top three outcome concerns raised by patients were medication side effects/muscle weakness/prevention functionality loss. The top three concerns among rheumatologists were to prevent loss of functionality/to ensure the quality of life/to achieve disease remission. Other's outcomes concerns only pointed out by patients were muscle pain/diffuse pain/skin lesions/fatigue. The agreement rate between both groups was 41%. Assessment of these parameters guided the development of an IIM standard set which included Myositis Disease Activity Assessment Visual Analogue Scale/Manual Muscle Testing/fatigue and pain Global Visual Analogue Scale/Health Assessment Questionnaire/level of physical activity. Conclusion The authors propose a novel standard set to be pursued in IIM routine follow-up, which includes not only the main patients/rheumatologist outcome concerns but also additional important outcomes only indicated by patients. Future studies are necessary to confirm if this comprehensive approach will result in improved adherence and ultimately in better assistance.
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OBJECTIVES: To retrospectively evaluate the performance and distinctive pattern of latent tuberculosis (TB) infection (LTBI) screening and treatment in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) under anti-tumor necrosis factor (TNF) therapy and determine the relevance of re-exposure and other risk factors for TB development. METHODS: A total of 135 and 83 patients with AS and PsA, respectively, were evaluated for LTBI treatment before receiving anti-TNF drugs via the tuberculin skin test (TST), chest radiography, and TB exposure history assessment. All subjects were evaluated for TB infection at 3-month intervals. RESULTS: The patients with AS were more often treated for LTBI than were those with PsA (42% versus 30%, p=0.043). The former also presented a higher frequency of TST positivity (93% versus 64%, p=0.002), although they had a lower frequency of exposure history (18% versus 52%, p=0.027) and previous TB (0.7% versus 6%, p=0.03). During follow-up [median, 5.8 years; interquartile range (1QR), 2.2-9.0 years], 11/218 (5%) patients developed active TB (AS, n=7; PsA, n=4). TB re-exposure was the main cause in seven patients (64%) after 12 months of therapy (median, 21.9 months; IQR, 14.2-42.8 months) and five LTBI-negative patients. TB was identified within the first year in four patients (36.3%) (median, 5.3 months; IQR, 1.2-8.8 months), two of whom were LTBI-positive. There was no difference in the TB-free survival according to the anti-TNF drug type/class; neither synthetic drug nor prednisone use was related to TB occurrence (p>0.05). CONCLUSION: Known re-exposure is the most critical factor for incident TB cases in spondyloarthritis. There are also some distinct features in AS and PsA LTBI screening, considering the higher frequency of LTBI and TST positivities in patients with AS. Annual risk reassessment taking into consideration these peculiar features and including the TST should be recommended for patients in endemic countries.
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Humanos , Espondilite Anquilosante/tratamento farmacológico , Artrite Psoriásica/diagnóstico , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/epidemiologia , Tuberculose Latente/diagnóstico , Tuberculose Latente/epidemiologia , Espondilite Anquilosante/epidemiologia , Estudos Retrospectivos , Seguimentos , Inibidores do Fator de Necrose Tumoral/uso terapêuticoRESUMO
Abstract Nailfold capillaroscopy (NFC) is a reproducible, simple, low-cost, and safe imaging technique used for morphological analysis of nail bed capillaries. It is considered to be extremely useful for the investigation of Raynaud's phenomenon and for the early diagnosis of systemic sclerosis (SSc). The capillaroscopic pattern typically associated with SSc, scleroderma ("SD") pattern, is characterized by dilated capillaries, microhemorrhages, avascular areas and/or capillary loss, and distortion of the capillary architecture. The aim of these recommendations is to provide orientation regarding the relevance of NFC, and to establish a consensus on the indications, nomenclature, the interpretation of NFC findings and the technical equipments that should be used. These recommendations were formulated based on a systematic literature review of studies included in the database MEDLINE (PubMed) without any time restriction.
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Humanos , Escleroderma Sistêmico/diagnóstico , Guias de Prática Clínica como Assunto , Vasoespasmo Coronário/diagnóstico , Angioscopia Microscópica/instrumentação , Esclerodermia Difusa/diagnósticoRESUMO
OBJECTIVES: To evaluate serum levels of C-reactive protein and erythrocyte sedimentation rates in patients with untreated newly diagnosed dermatomyositis or polymyositis and their correlation with clinical and laboratory parameters. METHODS: A cross-sectional study including 48 consecutive patients with untreated newly diagnosed dermatomyositis and polymyositis reviewed between 2002 and 2015 was conducted. Fifty healthy subjects were enrolled as controls. RESULTS: Patients with dermatomyositis and polymyositis had higher levels of C-reactive protein and erythrocyte sedimentation rate than healthy controls, but these values were not associated with clinical or laboratory parameters of disease activity either for dermatomyositis or for polymyositis. Additionally, erythrocyte sedimentation rate values correlated with pulmonary involvement as evidenced through computer tomography imaging (OR 1.15; 95%CI 1.01-1.31) only in patients with polymyositis. CONCLUSIONS: Although elevated, C-reactive protein and erythrocyte sedimentation rate are not sensitive parameters for measuring clinical and laboratory activity of dermatomyositis nor for polymiositis. However, erythrocyte sedimentation rate may be a valid parameter for screening pulmonary involvement, particularly in patients with polymyositis.
OBJETIVOS: Avaliar os níveis séricos da proteína C reativa (PCR) e da velocidade de hemossedimentação (VHS) em pacientes recém-diagnosticados com dermatomiosite (DM) e polimiosite (PM), sem tratamento prévio, correlacionando-os com parâmetros clínico-laboratoriais. MÉTODOS: Estudo transversal que incluiu 48 pacientes consecutivos com DM e PM (critérios de Bohan e Peter) recém-diagnosticados, sem tratamento medicamentoso, no período de 2002 a 2015. Foram incluídos 50 indivíduos saudáveis como grupo controle. RESULTADOS: Os pacientes apresentaram níveis mais elevados de VHS e PCR comparativamente aos controles saudáveis. Estes valores, porém, não se correlacionaram com os parâmetros clínicos e laboratoriais da atividade da doença (DM e PM). Somente em pacientes com PM a VHS apresentou relação com acometimento pulmonar na tomografia computadorizada [OR 1,15 (IC 95% 1,01-1,31)]. CONCLUSÕES: Apesar de aumentadas, a PCR e a VHS não são parâmetros sensíveis para a mensuração da atividade clínica e laboratorial de DM e PM., No entanto, a VHS pode ter validade no rastreio do acometimento pulmonar, particularmente em pacientes com PM.
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Humanos , Proteína C-Reativa/análise , Polimiosite , Dermatomiosite , Sedimentação Sanguínea , Estudos Transversais , Pneumopatias/etiologiaRESUMO
Abstract Introduction: To date, there are no descriptions in the literature on gynecologic and sexual function evaluation in female patients with dermatomyositis (DM) and polymyositis (PM). Objective: To assess sexual function in female patients with DM/PM. Patients and methods: This is a monocentric, cross-sectional study in which 23 patients (16 DM and 7 PM), with ages between 18 and 40 years, were compared to 23 healthy women of the same age group. Characteristics on sexual function were obtained by applying the questionnaires Female Sexual Quotient (FSQ) and Female Sexual Function Index (FSFI) validated for the Brazilian Portuguese language. Results: The mean age of patients was comparable to controls (32.7 ± 5.3 vs. 31.7 ± 6.7 years), as well as the distribution of ethnicity and socioeconomic class. As for gynecological characteristics, patients and healthy controls did not differ with respect to age at menarche and percentages of dysmenorrhea, menorrhagia, premenstrual syndrome, pain at mid-cycle, mucocervical secretion, and vaginal discharge. The FSQ score, as well as all domains of the FSFI questionnaire (desire, arousal, lubrication, orgasm and satisfaction), were significantly decreased in patients vs. controls, with 60.9% of patients showing some degree of sexual dysfunction. Conclusions: This was the first study to identify sexual dysfunction in patients with DM/PM. Therefore, a multidisciplinary approach is essential for patients with idiopathic inflammatory myopathies, in order to provide prevention and care for their sexual life, providing a better quality of life, both for patients and their partners.
Resumo Introdução: Até o presente momento, não há descrições na literatura da avaliação ginecológica e da função sexual em pacientes do sexo feminino com dermatomiosite (DM) e polimiosite (PM). Objetivos: Avaliar a função sexual em pacientes do sexo feminino com DM/PM. Casuística e métodos: Estudo transversal unicêntrico em que 23 pacientes (16 DM e sete PM), entre 18 e 40 anos, foram comparadas com 23 mulheres saudáveis, com a mesma faixa etária. As características sobre a função sexual foram obtidas por meio da aplicação dos questionários Female Sexual Quotient (FSQ) e Female Sexual Function Index (FSFI) validados para a língua portuguesa do Brasil. Resultados: A média de idade das pacientes foi comparável à dos controles (32,7 ± 5,3 vs. 31,7 ± 6,7 anos), assim como a distribuição de etnia e da classe socioeconômica. Quanto às características ginecológicas, pacientes e controles saudáveis não apresentaram diferenças em relação à idade na menarca e às porcentagens de dismenorreia, menorragia, síndrome pré-menstrual, dor no meio do ciclo, secreção mucocervical e corrimento vaginal. O escore de pontuação do FSQ, assim como todos os domínios do questionário do FSFI (desejo, excitação, lubrificação, orgasmo e satisfação), estavam significantemente diminuídos nas pacientes comparativamente com os controles, 60,9% das pacientes apresentavam algum grau de disfunção sexual. Conclusões: Este foi o primeiro estudo que identificou disfunção sexual nas pacientes com DM/PM. Assim, uma abordagem multidisciplinar é essencial para pacientes com miopatias inflamatórias idiopáticas para fornecer medidas de prevenção e cuidados para sua vida sexual e propiciar uma melhor qualidade de vida das pacientes e de seus parceiros.
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Humanos , Feminino , Adulto , Adulto Jovem , Disfunções Sexuais Fisiológicas/complicações , Disfunções Sexuais Fisiológicas/fisiopatologia , Inquéritos e Questionários , Polimiosite/complicações , Polimiosite/fisiopatologia , Disfunções Sexuais Psicogênicas/complicações , Disfunções Sexuais Psicogênicas/fisiopatologia , Dermatomiosite/complicações , Dermatomiosite/fisiopatologia , Qualidade de Vida , Disfunções Sexuais Fisiológicas/psicologia , Disfunções Sexuais Fisiológicas/epidemiologia , Brasil/epidemiologia , Comorbidade , Estudos Transversais , Polimiosite/psicologia , Polimiosite/epidemiologia , Disfunções Sexuais Psicogênicas/psicologia , Disfunções Sexuais Psicogênicas/epidemiologia , Dermatomiosite/psicologia , Dermatomiosite/epidemiologiaRESUMO
ABSTRACT Introduction: Cardiac involvement is frequent in inflammatory myopathies. Electrocardiogram (ECG) may show evidence of this involvement and its changes should be well-known and described. Objectives: Due to the lack of studies in the literature, we conducted an analysis of the ECG findings in patients with dermatomyositis (DM) and polymyositis (PM), comparing them with a control group. Methods: This cross-sectional study compared the ECG of 86 individuals with no rheumatic disorders (controls) with 112 patients (78 DM and 34 PM), during 2010 to 2013. The ECG findings between DM and PM were also compared. Results: Demographic characteristics, comorbidities and ECG abnormalities were similar between controls and patients (p > 0.05), except for a higher frequency of left ventricular hypertrophy (LVH) in patients (10.7% vs. 1.2%, p = 0.008). Demographic characteristics, comorbidities, clinical and laboratory manifestations, were also similar between the groups PM and DM, except for the presence of cutaneous lesions only in DM. One third of the patients had ECG abnormalities, which were more prevalent in PM than DM (50% vs. 24.4%, p = 0.008). LVH, left atrial enlargement, rhythm and conduction abnormalities were more frequent in PM than DM (p < 0.05 for all), especially the left anterior fascicular block. Conclusions: We showed distinct ECG changes between DM and PM and a higher frequency of LVH in patients compared to controls. Investigation of cardiac involvement should be considered even in asymptomatic patients, especially PM. Further studies are necessary in order to determine the correlation of ECG findings with other complementary tests, clinical manifestations, disease activity and progression to other cardiac diseases.
RESUMO Introdução: Acometimento cardíaco nas miopatias inflamatórias é frequente. Eletrocardiograma (ECG) pode mostrar indícios desse acometimento e suas alterações devem ser bem conhecidas e descritas. Objetivos: Devido à escassez de trabalhos na literatura, analisamos as alterações de ECG em pacientes com dermatomiosite (DM) e polimiosite (PM) e as comparamos com um grupo controle. Métodos: Este estudo transversal comparou ECGs de 86 indivíduos sem doenças reumatológicas (controles) com 112 pacientes (78 DM e 34 PM), de 2010 a 2013. Também comparamos os ECGs entre DM e PM. Resultados: Características demográficas, comorbidades e alterações de ECG foram semelhantes entre controles e pacientes (p > 0,05), exceto pela maior frequência de sobrecarga de ventrículo esquerdo (SVE) nos pacientes (10,7% vs. 1,2%; p = 0,008). Características demográficas, comorbidades, manifestações clínicas e laboratoriais também foram semelhantes entre os grupos PM e DM, exceto por lesões cutâneas apenas em pacientes com DM. Um terço dos pacientes apresentou alterações de ECG, que foram mais prevalentes em PM do que em DM (50% vs. 24,4%, p = 0,008). Sobrecarga de câmaras esquerdas (SCE), distúrbios do ritmo e da condução foram mais encontrados em PM do que em DM (p < 0,05 para todos), sobretudo o bloqueio divisional do ramo anterossuperior. Conclusões: Encontramos alterações distintas de ECG entre PM e DM e frequência aumentada de SVE em pacientes quando comparados com controles. Investigação do acometimento cardíaco nessas doenças deve ser considerada mesmo em pacientes assintomáticos, especialmente em se tratando de PM. Mais estudos são necessários para correlacionar os achados de ECG com outros exames complementares, manifestações clínicas, atividade das miopatias e evolução para outras doenças cardíacas.
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Humanos , Polimiosite/diagnóstico , Dermatomiosite/diagnóstico , Eletrocardiografia/métodos , Estudos de Casos e Controles , Estudos Transversais , CoraçãoRESUMO
OBJECTIVE: To assess the potential acute effects regarding the immunogenicity and safety of non-adjuvanted influenza A H1N1/2009 vaccine in patients with mixed connective tissue disease and healthy controls. METHODS: Sixty-nine mixed connective tissue disease patients that were confirmed by Kasukawa's classification criteria and 69 age- and gender-matched controls participated in the study; the participants were vaccinated with the non-adjuvanted influenza A/California/7/2009 (H1N1) virus-like strain. The percentages of seroprotec-tion, seroconversion, geometric mean titer and factor increase in the geometric mean titer were calculated. The patients were clinically evaluated, and blood samples were collected pre- and 21 days post-vaccination to evaluate C-reactive protein, muscle enzymes and autoantibodies. Anti-H1N1 titers were determined using an influenza hemagglutination inhibition assay. ClinicalTrials.gov: NCT01151644. RESULTS: Before vaccination, no difference was observed regarding the seroprotection rates (p = 1.0) and geometric mean titer (p = 0.83) between the patients and controls. After vaccination, seroprotection (75.4% vs. 71%, (p = 0.7), seroconversion (68.1% vs. 65.2%, (p = 1.00) and factor increase in the geometric mean titer (10.0 vs. 8.0, p = 0.40) were similar in the two groups. Further evaluation of seroconversion in patients with and without current or previous history of muscle disease (p = 0.20), skin ulcers (p = 0.48), lupus-like cutaneous disease (p = 0.74), secondary Sjogren syndrome (p = 0.78), scleroderma-pattern in the nailfold capillaroscopy (p = 1.0), lymphopenia #1000/mm³ on two or more occasions (p = 1.0), hypergammaglobulinemia $1.6 g/d (p = 0.60), pulmonary hypertension (p = 1.0) and pulmonary fibrosis (p = 0.80) revealed comparable rates. Seroconversion rates were also similar in patients with and without immunosuppressants. Disease parameters, such as C-reactive protein (p = 0.94), aldolase (p = 0.73), creatine phosphokinase (p = 0.40) and ribonucleoprotein antibody levels (p = 0.98), remained largely unchanged pre and post-vaccination. No severe side effects were reported. CONCLUSIONS: The non-adjuvanted influenza A/H1N1 vaccination immune response in mixed connective tissue disease patients is adequate and does not depend on the disease manifestations and therapy.
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Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vírus da Influenza A Subtipo H1N1/imunologia , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Doença Mista do Tecido Conjuntivo/imunologia , Estudos de Casos e Controles , Vacinas contra Influenza/efeitos adversos , Estatísticas não Paramétricas , Fatores de TempoRESUMO
Avaliar os efeitos de um preparado injetavel mensal contendo enantato de noretisterona 50 mg + valerato de estradiol 5 mg, sobre os niveis pressoricos e...
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Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Injeções Intramusculares/métodos , Menopausa , Terapia de Reposição Hormonal/métodos , Hipertensão/etiologia , Noretindrona , Fatores de TempoRESUMO
O complexo esclerose tuberosa (TSC) e uma doenca rara de manifestacao sistemica que...