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OBJECTIVES: - Janus Kinase inhibitors (JAKi) are a new class of drugs available for pediatric rheumatic diseases. This study aimed to describe the safety and effectiveness of JAKi in these diseases, with a focus on longitudinal interferon-stimulated genes (ISG) assessment. METHODS: - We present a single-center retrospective study of children with refractory pediatric rheumatic diseases including connective tissue diseases, monogenic type I interferonopathies or juvenile idiopathic arthritis, receiving JAKi. According to physicians' assessment, treatment effectiveness was classified at 12 months as a complete response in the total absence of disease activity, partial response in case of significant (>50%) but incomplete improvement or no response in the case of non-response or improvement of less than 50% of the clinical and biological parameters. ISG were monitored longitudinally using Nanostring technology. RESULTS: - 22 children were retrospectively included in this study, treated either by baricitinib or ruxolitinib. Complete response was achieved at 12 months in 9/22 (41%) patients. 6/22 (27%) patients were non-responders and treatment had been discontinued in five of them. Within the interferon (IFN)-related diseases group, ISG-score was significantly reduced 12 months after JAKi onset (p = 0.0068). At 12 months, daily glucocorticoid doses had been reduced with a median dose of 0.16 mg/kg/day (IQR 0.11; 0.33) (p = 0.0425). 7/22 (32%) patients had experienced side effects, infections being the most common. Increase of the body mass index was also recorded in children in the first 6 months of treatment. CONCLUSION: - JAKi represent a promising treatment of immune-mediated pediatric diseases, enabling to decrease type-I IFN transcriptomic signature in responding patients, especially in the context of juvenile dermatomyositis. JAKi represent steroid-sparing drugs but they induce metabolic changes linked to weight gain, posing a concern in the treatment of young patients and teenagers. More data are required to define the efficacy and safety of JAKi in the management of refractory pediatric rheumatic diseases.
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Interferon Tipo I , Inibidores de Janus Quinases , Humanos , Estudos Retrospectivos , Criança , Masculino , Feminino , Inibidores de Janus Quinases/uso terapêutico , Inibidores de Janus Quinases/efeitos adversos , Adolescente , Resultado do Tratamento , Interferon Tipo I/metabolismo , Pré-Escolar , Pirazóis/uso terapêutico , Pirazóis/efeitos adversos , Purinas/uso terapêutico , Pirimidinas/uso terapêutico , Azetidinas/uso terapêutico , Artrite Juvenil/tratamento farmacológico , Sulfonamidas/uso terapêutico , Doenças Reumáticas/tratamento farmacológico , Nitrilas/uso terapêuticoRESUMO
Introducción: El cáncer de tiroides es una enfermedad frecuente en el mundo, con mayor prevalencia del tipo diferenciado. El diagnóstico temprano y manejo pertinente, individualizado y adaptable puede mejorar su pronóstico. Objetivo: Generar recomendaciones basadas en evidencia sobre el tratamiento y seguimiento de personas adultas con cáncer diferenciado de tiroides (CDT). Metodología: Guía de práctica clínica (GPC) a partir de revisión sistemática de literatura (RSL) y consenso de expertos clínicos. El grupo desarrollador definió el alcance y cuatro preguntas que se resolvieron a través de revisión de evidencia de GPC existentes, RSL, estudios primarios publicadas en español o inglés en diferentes fuentes de información desde 2013. Las preguntas de investigación fueron: 1. ¿Cuáles son las indicaciones de la vigilancia activa?, ¿cómo realizarla?, ¿cuándo y con que periodicidad realizarla? 2. ¿Cuál es el tratamiento y su indicación en pacientes con nódulos tiroideos sospechosos de cáncer? 3. ¿Cómo y cuándo realizar seguimiento de pacientes con CDT de acuerdo con el riesgo dinámico? 4. ¿Cuál es el manejo actual de los pacientes iodo refractarios? Se propusieron recomendaciones basadas en la evidencia, y analizadas y discutidas por el colectivo experto en sesiones asincrónicas. Se evalúo la calidad de la evidencia y las recomendaciones fueron gradadas en fuerte o condicional y a favor o en contra a partir del análisis de la calidad de la evidencia, contexto de implementación (disponibilidad e implementación) y la experticia clínica. En el presente documento se desarrollada la primera pregunta, referente a vigilancia activa. Resultados: 86 recomendaciones fueron propuestas y acordadas por el grupo desarrollador, categorizadas en tratamiento y seguimiento para resolver las preguntas planteadas. 10 de las recomendaciones corresponden a vigilancia activa y se incluyen en el presente documento. Recomendaciones claves incluyen, brindar información completa y oportuna a pacientes, conformación de equipos multidisciplinarios, análisis individualizado del paciente para la decisión de tratamiento, estadificación rutinaria de riesgo dinámico para evaluar la respuesta al tratamiento y ajustarlo, minimización de procedimientos fútiles o que aportan poco a la supervivencia y calidad de vida de los pacientes. Conclusión: Se presentan recomendaciones que esperan incidir en la estandarización de la práctica clínica cotidiana de pacientes con CDT y mejores resultados en salud.
Introduction: Thyroid cancer is a common disease in the world, with a higher prevalence of the differentiated type. Early diagnosis individualized and adaptive management can improve prognosis. Objective: Generate evidence-based recommendations on the treatment and follow-up of adults with differentiated thyroid carcinoma (DTC). Methodology: Clinical practice guideline (CPG) based on systematic literature review (RSL) and consensus of clinical experts. The development group defined the range and four questions that were resolved through a review of evidence from existing CPGs, RSLs, primary studies published in Spanish or English in various sources of information since 2013. The research questions were: 1. What are the indications for active surveillance? How to carry it out? When and how often to carry it out? 2. What is the treatment and its indication in patients with thyroid nodules suspicious for cancer? 3. How and when to follow up patients with CDT according to dynamic risk? 4. What is the current management of iodine refractory patients? Evidence-based recommendations analyzed and discussed by the expert group in asynchronous sessions were proposed. The quality of the evidence was evaluated, and the recommendations were graded as strong or conditional and in favor or against based on the analysis of the quality of the evidence, implementation context (availability and implementation) and clinical expertise. In this document, is developed the first question, referring to active surveillance. Results: 86 recommendations were proposed and agreed upon by the development group, categorized into treatment and follow-up to solve the questions raised. 10 of the recommendations correspond to active surveillance and are included in this document. Key recommendations include providing complete and timely information to patients, develop of multidisciplinary teams, individualized patient analysis for treatment decisions, routine dynamic risk staging to evaluate response to treatment and adjust it, minimization of futile procedures or that contribute little to the survival and quality of life of patients. Conclusion: Recommendations are presented that longs to influence the standardization of the daily clinical practice of patients with DTC and better health outcomes.
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OBJECTIVE: To evaluate the risk of global infections in patients with psoriatic arthritis (PsA) and axial spondyloarthritis encompassing ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA) treated with targeted therapies. METHODS: Medline and Cochrane databases were systematically searched up to March 2021 for randomized controlled trials (RCTs) performed in patients with PsA or axial spondyloarthritis treated with biologic or targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs). Global infections (any infections reported, including bacterial, viral and fungal infections, except serious infections) were the primary outcome. Secondary outcomes included serious infections defined as life-threatening infections or any infection requiring intravenous antibiotics or hospitalization. The relative risk of infections was determined by meta-analysis of RCTs. RESULTS: A total of 60 RCTs were included (20,418 patients), encompassing 17 b/tsDMARDs, compared with placebo, conventional synthetic drugs (csDMARDs) or non-steroidal anti-inflammatory drugs (NSAIDs). An increased risk of any infection for patients exposed to these drugs was found (RR 1.15, 95% CI [1.06-1.25]), mainly with high doses and longer duration of treatment. Most infections were respiratory tract or ear, nose, and throat (ENT) infections. Subgroup analyses showed a statistically significant increased risk of infections for axial spondyloarthritis patients (RR 1.32, 95% CI [1.14-1.52]), but not for PsA patients (RR 1.05, 95% CI [0.97-1.14]). Infection risk was highest with TNF inhibitors (RR 1.23, 95% CI [1.11-1.37]) and IL-17 inhibitors (RR 1.30, 95% CI [1.07-1.59]). No increased risk of serious infections was shown. CONCLUSION: In contrast to serious infections, the risk of global infections is moderately increased with b/tsDMARDs in spondyloarthritis, and is associated in particular with use of TNF and IL-17 inhibitors.
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OBJECTIVE: To estimate the incidence of infections among patients with psoriatic arthritis (PsA) or axial spondyloarthritis (axSpA), two distinct phenotypes included in the large group of spondyloarthritis (SpA), treated with tumour necrosis-factor-inhibitors, interleukin-17-inhibitors, Janus kinase-inhibitors, IL-23 or IL-12/23-inhibitors (IL-12/23i), phosphodiesterase 4-inhibitors or cytotoxic T-lymphocyte associated protein 4-Ig. METHODS: A meta-analysis of randomised controlled trials (RCTs), open-label extension and observational studies was conducted. Serious infections were defined as infections that were life-threatening, required intravenous antibiotics and/or hospitalisation. Non-serious infections did not meet these severity criteria. The incidence rates (IR) were reported for each diagnosis by treatment class and study type using random-effect model to create a 95% CI. RESULTS: Among 23 333 PsA patients and 11 457 axSpA patients, there were 1.09 serious infections per 100 patient-years (PY) (95% CI 0.85 to 1.35) with similar IR in PsA (0.96 per 100 PY 95% CI 0.69 to 1.28) and axSpA (1.09 per 100 PY 95% CI 0.76 to 1.46). The IR was lower in RCTs (0.77 per 100 PY 95% CI 0.41 to 1.20) compared with observational studies (1.68 per 100 PY 95% CI 1.03 to 2.47). In PsA patients, the lowest IR value was observed with IL-12/23i (0.29 per 100 PY 95% CI 0.00 to 1.03). There were 53.0 non-serious infections per 100 PY (95% CI 43.47 to 63.55) in 7257 PsA patients and 5638 axSpA patients. The IR was higher in RCTs (69.95 per 100 PY 95% CI 61.59 to 78.84) compared with observational studies (15.37 per 100 PY 95% CI 5.11 to 30.97). CONCLUSION: Serious infections were rare events in RCTs and real-life studies. Non-serious infections were common adverse events, mainly in RCTs. PROSPERO REGISTRATION NUMBER: CRD42020196711.
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Artrite Psoriásica , Espondiloartrite Axial , Humanos , Artrite Psoriásica/complicações , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/epidemiologia , Incidência , Interleucina-12 , Projetos de Pesquisa , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND AND OBJECTIVE: The clinical and biochemical overlap of various pathologies of phosphocalcic metabolism can lead to misdiagnosis and consequent clinical management. One example is pseudohypoparathyroidism, which can be confused with vitamin D-dependent rickets (VDDR1) if appropriate biochemical determinations are not performed. PATIENTS AND METHODS: Two pairs of siblings, from independent families, were clinically diagnosed in adolescence with pseudohypoparathyroidism due to hypocalcaemia, elevated parathyroid hormone levels and normal or elevated phosphorus values. After ruling out alterations in GNAS, a massive sequencing study of genes associated with other differential diagnoses was carried out. RESULTS: Two genetic variants in the CYP27B1 gene potentially associated with the phenotype were identified. Pathogenic variants in this gene are associated with VDDR1A. Clinical-biochemical re-evaluation of the patients confirmed this diagnosis and treatment was adapted. CONCLUSIONS: Although VDDR1A is an infrequently diagnosed pathology in adulthood, in cases of hypocalcaemia with elevated PTH values, determination of the 1,25(OH)2D3 and 25(OH)D3 forms of vitamin D is relevant to reach a correct diagnosis.
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Hipocalcemia , Pseudo-Hipoparatireoidismo , Deficiência de Vitamina D , Adolescente , Humanos , Hipocalcemia/diagnóstico , Hipocalcemia/etiologia , Hormônio Paratireóideo , Deficiência de Vitamina D/complicações , Pseudo-Hipoparatireoidismo/diagnóstico , Pseudo-Hipoparatireoidismo/genética , Pseudo-Hipoparatireoidismo/complicações , Vitamina D/uso terapêuticoRESUMO
AIMS/HYPOTHESIS: Cardiovascular outcome trials (CVOTs) have demonstrated the benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i). However, serious adverse drug reactions have been reported. The risk/benefit ratio of SGLT2i remains unquantified. We aimed to provide an estimation of their risk/benefit ratio in individuals with type 2 diabetes. METHODS: We conducted a systematic review (MEDLINE, up to 14 September 2021) and meta-analysis. We included randomised CVOTs assessing SGLT2i in individuals with type 2 diabetes with or without other diseases. We used the Cochrane 'Risk of bias' assessment tool. The primary outcomes were overall mortality, major adverse cardiovascular events (MACE), hospitalisation for heart failure (HHF), end-stage renal disease (ESRD), amputation, diabetic ketoacidosis (DKA) and reported genital infections. For each outcome, we estimated the incidence rate ratio (IRR) with a 95% CI; we then computed the number of events expected spontaneously and with SGLT2i. RESULTS: A total of 46,969 participants from five double-blind, placebo-controlled international trials (weighted mean follow-up 3.5 years) were included. The prevalence of previous CVD ranged from 40.6% to 99.2%. The definition of reported genital infections ranged from 'genital mycotic infection' to 'genital infections that led to discontinuation of the trial regimen or were considered to be serious adverse events'. The number of included studies for each outcomes was five. The use of SGLT2i decreased the risk of all-cause death (IRR 0.86 [95% CI 0.78, 0.95]), MACE (IRR 0.91 [95% CI 0.86, 0.96]), HHF (IRR 0.69 [95% CI 0.62, 0.76]) and ESRD (IRR 0.67 [95% CI 0.53, 0.84]), and increased the risk of DKA (IRR 2.59 [95% CI 1.57, 4.27]) and genital infection (IRR 3.50 [95% CI 3.09, 3.95]) but not of amputation (IRR 1.23 [95% CI 1.00, 1.51]). For 1000 individuals treated over 3.5 years, SGLT2i are expected, on average, to decrease the number of deaths from 70 to 61, to prevent nine MACE, 11 HHF and two cases of ESRD, while inducing two DKA occurrences and 36 genital infections; 778 individuals are expected to avoid all the following outcomes: MACE, HHF, ESRD, amputation, DKA and genital infection. CONCLUSIONS/INTERPRETATION: Our study is limited to aggregate data. In a population of individuals with type 2 diabetes and a high CVD risk, the cardiovascular and renal benefits of SGLT2i remain substantial despite the risk of DKA and even the hypothetical risk of amputation. TRIAL REGISTRATION: OSF Registries: https://doi.org/10.17605/OSF.IO/J3R7Y FUNDING: This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.
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Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Cetoacidose Diabética , Insuficiência Cardíaca , Falência Renal Crônica , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Cetoacidose Diabética/tratamento farmacológico , Insuficiência Cardíaca/etiologia , Medição de Risco , Falência Renal Crônica/complicações , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
OBJECTIVES: To determine the characteristics of juvenile idiopathic arthritis (JIA) patients seen during the transition period in order to compare paediatric classification criteria with those for adults. METHODS: Patients with JIA according to the ILAR classification and who had a consultation at transition between 2010 and 2017 were included in a retrospective bi-centre (Lyon, Lausanne) study. JIA classification criteria were compared to ACR/EULAR 2010 criteria for rheumatoid arthritis (RA), Yamaguchi criteria for adult-onset Still's disease (AOSD), ASAS criteria for spondyloarthritis and CASPAR criteria for psoriatic arthritis. RESULTS: One hundred and thirty patients were included: 13.9% with systemic JIA, 22.3% with polyarticular JIA, 22.3% with oligoarticular JIA, 34.6% with enthesitis-related arthritis (ERA) and 6.9% with psoriatic arthritis; 13.1% had suffered from uveitis; 14.5% of patients had erosions or carpitis, mainly those with psoriatic arthritis, polyarticular or systemic JIA; 37.5% of patients with ERA displayed radiological sacroiliitis. When comparing paediatric JIA criteria with adult classifications, we found that: 66.6% of patients with systemic JIA fulfilled the criteria for AOSD, 87.5% of rheumatoid factor-positive polyarticular JIA and 9.5% of rheumatoid factor-negative polyarticular JIA met the criteria for RA, and 34.5% of oligoarticular JIA fulfilled the criteria for spondyloarthritis. Finally, 77.7% of patients with ERA met the criteria for spondyloarthritis, and 100% of patients with psoriatic arthritis JIA met the criteria for psoriatic arthritis. CONCLUSION: Oligoarticular JIA and rheumatoid factor-negative polyarticular JIA seem to be paediatric entities, whereas the other types of JIA tended to meet the respective adult classification criteria.
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Artrite Juvenil , Artrite Psoriásica , Artrite Reumatoide , Transição para Assistência do Adulto , Adulto , Artrite Juvenil/diagnóstico , Artrite Juvenil/epidemiologia , Artrite Psoriásica/diagnóstico , Artrite Psoriásica/epidemiologia , Criança , Humanos , Estudos RetrospectivosRESUMO
OBJECTIVE: To assess the net benefit of biological agents (BA) used in JIA. METHODS: We systematically searched databases up to March 2019 for randomized controlled trials (RCT) performed in JIA disease. Separate random-effects meta-analyses were conducted for efficacy (ACR paediatric score 30%, ACRpedi30) and serious adverse events for safety. In order to standardize the baseline risk, we performed a meta-analysis of baseline risk in the control group (for both efficacy and safety meta-analysis). The net benefit was determined as the risk difference of efficacy subtracted by the risk difference of safety. RESULTS: We included 19 trials: 11 parallel RCTs (754 patients) and 8 withdrawal RCTs (704 patients). The net benefit ranged from 2.4% (adalimumab) to 17.6% (etanercept), and from 2.4% (etanercept) to 36.7%, (abatacept) in parallel and withdrawal trials assessing non-systemic JIA, respectively. In the systemic JIA category, the net benefit ranged from 22.8% (rilonacept) to 70.3% (canakinumab), and from 32.3% (canakinumab) to 58.2% (tocilizumab) in parallel and withdrawal trials, respectively. CONCLUSION: The results suggest that a greater number of patients experienced therapeutic success without serious adverse events in the systemic onset JIA category compared with the BAs for non-systemic JIA categories. Baseline risk, design of trial and JIA categories impact the measure of net benefit of BAs in JIA patients.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Juvenil/tratamento farmacológico , Fatores Biológicos/uso terapêutico , Abatacepte/uso terapêutico , Adalimumab/uso terapêutico , Artrite Juvenil/imunologia , Criança , Etanercepte/uso terapêutico , Feminino , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Regressão , Medição de Risco , Resultado do TratamentoRESUMO
INTRODUCTION: The efficacy of rituximab (RTX) for remission induction and maintenance in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) is now established, but the safety, particularly concerning severe infection risk, is not well known. OBJECTIVE: The purpose of this meta-analysis is to assess the prevalence and incidence of severe infections and the factors explaining heterogeneity in AAV patients treated with RTX. METHODS: PubMed and Embase were searched up to December 2017. Prevalence and incidence was pooled using a random-effects model in case of significant heterogeneity (I2 > 50%). Severe infection was defined as severe when it led to hospitalization, intravenous antibiotics therapy, and/or death. The heterogeneity was explored by subgroup analyses and meta-regression. RESULTS: The included studies encompassed 1434 patients with a median age of 51.9 years. The overall prevalence and incidence of severe infections was 15.4% (95% CI [8.9; 23.3], I2 = 90%, 33 studies) and 6.5 per 100 person-years (PY) (95% CI [2.9; 11.4], I2 = 76%, 18 studies), respectively. The most common infections were bacterial (9.4%, 95% CI [5.1; 14.8]). The prevalence of opportunistic infection was 1.5% (95% CI [0.5; 3.1], I2 = 58%) including pneumocytis jirovecii infections (0.2%, 95% CI [0.0; 0.6], I2 = 0), irrespective of prophylaxis administration. Mortality related to infection was estimated at 0.7% (95% CI [0.2; 1.2], I2 = 27%). The RTX cumulative dose was positively associated with prevalence of infections (13 studies, prevalence increase of 4% per 100 mg, p < .0001). The incidence of infection was negatively associated with duration of follow-up (8 studies, incidence decrease of 9% per year, p = .03). CONCLUSION: Prevalence and incidence of severe infections, mainly bacterial ones, were high in AAV patients treated with RTX. This meta-analysis highlights the need for prospective studies to stratify infectious risk and validate cumulative RTX dose and duration of follow-up as modifying factors.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Infecções/complicações , Rituximab/uso terapêutico , Humanos , Pessoa de Meia-Idade , Indução de Remissão , Resultado do TratamentoRESUMO
OBJECTIVES: The main objective of our study is to assess the infectious adverse events occurring in juvenile idiopathic arthritis (JIA) children treated with biological agents. METHODS: Patients were selected from the retrospective module of the JIRcohorte, data concerning the period between January 2001 and August 2015. All infectious adverse events (IAE) were retrieved. For every infectious side effect, the date, the severity, the need for a hospitalization, the type of pathogen and the affected organ were noted. Incidence rates were expressed in number of events per 100 person-years (100p-y), and OR were calculated. RESULTS: Six hundred seventy-seven patients with JIA were included in the study. A total of 3075.4 person-years of exposure were analyzed. One hundred eighty-four infectious events were described (6.0 events/100 p-y): 15.5/100 p-y with tocilizumab (TCZ), 9.6/100 p-y with Canakinumab (CAN), 7.4/100 p-y with abatacept (ABA), 6.9/100 p-y with Golimumab (GOL), 6.7/100 p-y with Anakinra (ANA), 6.3/100 p-y with Infliximab, 4.8/100 p-y with Etanercept, and 3.7/100 p-y with Adalimumab. Risk of developing an infection was significantly higher with IL-6 antagonists or IL-1 antagonists than with TNF-inhibitor. Forty point eight percent of the infectious adverse events (IAE) affected the upper respiratory tract or the Ear, nose and throat (ENT) system. Twelve infectious adverse events were described as severe or very severe (0.4/100p-y). No case of tuberculosis or death was reported. CONCLUSION: Infectious complications with biologics occurring in children treated for JIA are rare, and in most of the cases have a mild or moderate severity, affecting mainly the upper respiratory tract or the ENT.
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Antirreumáticos , Artrite Juvenil , Produtos Biológicos , Infecções/epidemiologia , Adalimumab/uso terapêutico , Antirreumáticos/efeitos adversos , Artrite Juvenil/tratamento farmacológico , Artrite Juvenil/epidemiologia , Produtos Biológicos/efeitos adversos , Criança , Etanercepte/uso terapêutico , Humanos , Estudos RetrospectivosRESUMO
OBJECTIVE: The present literature review aims to highlight gaps in the treatment of preventative mother-to-child HIV transmission and the risk factors in Brazil. METHODS: Among the 425 articles identified in SciELO and PubMed searches, 59 articles published between 1994 and 2016 were selected for reading and data extraction, and 33 articles were included in the present review. RESULTS: The rates of vertical HIV transmission described in the studies varied widely, from 1.8% to 27.8%, with a significant reduction over the years. However, recent rates were also found to be variable in different regions of Brazil, and despite the significant reduction in mother-to-child transmission, many gaps remain in prevention services. A failure to attend prenatal care is the main factor associated with the increased risk of vertical transmission of HIV, hindering early maternal diagnosis and the completion of preventative measures during the prenatal period and, often, the peripartum and postnatal periods. A small number of studies discussed the sociodemographic factors, including a low level of education for pregnant women and the inadequacies of health services, such as difficulties scheduling appointments and undertrained staff, associated with vertical transmission. As such, the current challenge is to better define the sociodemographic and infrastructural factors that increase the risk of mother-to-child transmission of HIV to provide the necessary investments to promote an earlier inclusion of these populations in prevention services. CONCLUSIONS: This review may serve as a guide for future programs to focus efforts on the prevention of vertical HIV transmission.
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Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/transmissão , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Complicações Infecciosas na Gravidez/tratamento farmacológico , Brasil , Quimioterapia Combinada , Feminino , Infecções por HIV/prevenção & controle , Humanos , Gravidez , Cuidado Pré-Natal , Fatores de Risco , Zidovudina/uso terapêuticoRESUMO
Methotrexate has demonstrated its efficiency for the treatment of juvenile localized scleroderma but some patients may be resistant. The aim of our study was to define the profile of such patients. We performed an observational retrospective multicenter study between 2007 and 2016 and included all children seen in the French Paediatric Dermatology and Rheumatology departments with active localized scleroderma treated by methotrexate for a minimum of 4 months. Metho-trexate efficacy was assessed clinically and/or by imaging between the fourth to twelfth months of treatment. A total of 57 patients were included. Metho-trexate dosage ranged from 7 to 15 mg/m2/week. Only 4 patients were resistant. No common features could be identified between these 4 patients. Children with localized scleroderma are rarely resistant to metho-trexate and we did not identify a clinical profile for those resistant patients.
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Fármacos Dermatológicos/uso terapêutico , Resistência a Medicamentos , Metotrexato/uso terapêutico , Esclerodermia Localizada/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos RetrospectivosRESUMO
Around 1/1000 people have a solitary kidney. Congenital conditions mainly include multicystic dysplastic kidney and unilateral renal aplasia/agenesis; acquired conditions are secondary to nephrectomy performed because of urologic structural abnormalities, severe parenchymal infection, renal trauma, and renal or pararenal tumors. Children born with congenital solitary kidney have a better long-term glomerular filtration rate than those with solitary kidney secondary to nephrectomy later in life. Acute and chronic adaptation processes lead to hyperfiltration followed by fibrosis in the remnant kidney, with further risk of albuminuria, arterial hypertension, and impaired renal function. Protective measures rely on non-pharmacological renoprotection (controlled protein and sodium intake, avoidance/limitation of nephrotoxic agents, keeping normal body mass index, and limitation of tobacco exposure). Lifelong monitoring should include blood pressure and albuminuria assessment, completed by glomerular filtration rate (GFR) estimation in case of abnormal values. In the absence of additional risk factors to solitary kidney, such assessment can be proposed every 5 years. There is no current consensus for indication and timing of pharmacological intervention.
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Adaptação Fisiológica , Taxa de Filtração Glomerular/fisiologia , Neoplasias Renais/cirurgia , Rim/fisiopatologia , Rim Único/fisiopatologia , Adulto , Animais , Criança , Ensaios Clínicos como Assunto , Modelos Animais de Doenças , Humanos , Hipertrofia/etiologia , Hipertrofia/fisiopatologia , Hipertrofia/terapia , Rim/anormalidades , Rim/lesões , Rim/cirurgia , Nefrectomia/efeitos adversos , Rim Único/etiologia , Rim Único/terapiaRESUMO
OBJECTIVE: To analyse and report the incidence of side effects of biological agents in paediatric patients with inflammatory diseases using of real-life follow-up cohort. METHODS: In this international, observational, retrospective, multicentre study of children treated by biological agents and followed in the Juvenile Inflammatory Rheumatism (JIR) cohort (JIRcohorte) network, a Kaplan-Meier method was used to estimate the occurrence of adverse events. A Cox model was constructed to identify independent predictors of adverse events. RESULTS: Overall 813 patients totalling 3439 patients-year (PY) of biological agents were included. The main diagnosis was juvenile idiopathic arthritis (84%). A total of 222 patients (27.3%) had 419 adverse events, representing an incidence rate of 12.2 per 100 PY 95% CI [11.0; 13.4]. The overall incidence rate of serious adverse events was 3.9 per 100 PY 95% CI [3.2; 4.6]. Tocilizumab and infliximab were significantly associated with adverse events and canakinumab with serious adverse events. Univariate and multivariable analysis of adverse events and serious adverse events indicated that patients under biological agents with concomitant immunosuppressive drugs (excluding methotrexate) suffered from more of these events. CONCLUSION: This study suggests an overall an acceptable safety of biologic agents in children with inflammatory rheumatic diseases treated with biological agents. However, the concomitant prescription of immunosuppressive drugs with biological agents represents a substantial risk of adverse events.
Assuntos
Antirreumáticos/uso terapêutico , Artrite Juvenil/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Fatores Biológicos/uso terapêutico , Amplitude de Movimento Articular/efeitos dos fármacos , Abatacepte/efeitos adversos , Abatacepte/uso terapêutico , Adolescente , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Artrite Juvenil/diagnóstico , Artrite Reumatoide/diagnóstico , Criança , Pré-Escolar , Estudos de Coortes , Bases de Dados Factuais , Etanercepte/efeitos adversos , Etanercepte/uso terapêutico , Feminino , Humanos , Infliximab/efeitos adversos , Infliximab/uso terapêutico , Internacionalidade , Estimativa de Kaplan-Meier , Masculino , Análise Multivariada , Medição da Dor/efeitos dos fármacos , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Resultado do TratamentoRESUMO
OBJECTIVE: The present literature review aims to highlight gaps in the treatment of preventative mother-to-child HIV transmission and the risk factors in Brazil. METHODS: Among the 425 articles identified in SciELO and PubMed searches, 59 articles published between 1994 and 2016 were selected for reading and data extraction, and 33 articles were included in the present review. RESULTS: The rates of vertical HIV transmission described in the studies varied widely, from 1.8% to 27.8%, with a significant reduction over the years. However, recent rates were also found to be variable in different regions of Brazil, and despite the significant reduction in mother-to-child transmission, many gaps remain in prevention services. A failure to attend prenatal care is the main factor associated with the increased risk of vertical transmission of HIV, hindering early maternal diagnosis and the completion of preventative measures during the prenatal period and, often, the peripartum and postnatal periods. A small number of studies discussed the sociodemographic factors, including a low level of education for pregnant women and the inadequacies of health services, such as difficulties scheduling appointments and undertrained staff, associated with vertical transmission. As such, the current challenge is to better define the sociodemographic and infrastructural factors that increase the risk of mother-to-child transmission of HIV to provide the necessary investments to promote an earlier inclusion of these populations in prevention services. CONCLUSIONS: This review may serve as a guide for future programs to focus efforts on the prevention of vertical HIV transmission.
Assuntos
Humanos , Feminino , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Infecções por HIV/transmissão , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Fármacos Anti-HIV/uso terapêutico , Cuidado Pré-Natal , Brasil , Zidovudina/uso terapêutico , Infecções por HIV/prevenção & controle , Fatores de Risco , Quimioterapia CombinadaRESUMO
BACKGROUND: Despite great progress made in methods to prevent mother-to-child transmission of HIV (MTCT), delivery and uptake of these measures remains a challenge in many countries. Although the Brazilian Ministry of Health aimed to eliminate MTCT by 2015, infection still occured in 15-24% of infants born to HIV-infected mothers. We sought to identify remaining factors that constrain MTCT elimination. METHODS: We conducted a retrospective, matched case-control study by reviewing hospital charts of infants born to HIV-infected mothers between 1997 and 2014 at three MTCT reference hospitals in the Rio de Janeiro metropolitan area. Cases were defined as HIV-exposed children with two positive HIV tests before 18 months of age; controls were defined as HIV-exposed children with two negative HIV tests before 18 months of age. We performed bivariate and MTCT cascade analyses to identify risk factors for MTCT and gaps in prevention services. RESULTS: We included 435 infants and their mothers (145 cases, 290 controls). Bivariate analyses of MTCT preventative care (PMTCT) indicated that cases were less likely to complete all individual measures in the antenatal, delivery, and postnatal period (p < 0.05). Assessing completion of the PMTCT cascade, the sequential steps of PMTCT interventions, we found inadequate retention in care among both cases and controls, and cases were significantly less likely than controls to continue receiving care throughout the cascade (p < 0.05). Motives for incompletion of PMTCT measures included infrastructural issues, such as HIV test results not being returned, but were most often due to lack of care-seeking. Over the course of the study period, PMTCT completion improved, although it remained below the 95% target for antenatal care, HIV testing, and antenatal ART set by the WHO. Adding concern, evaluation of co-infections indicated that case infants were also more likely to have congenital syphilis (OR: 4.29; 95% CI: 1.66 to 11.11). CONCLUSIONS: While PMTCT coverage has improved over the years, completion of services remains insufficient. Along with interventions to promote care-seeking behaviour, increased infrastructural support for PMTCT services is needed to meet the HIV MTCT elimination goal in Brazil as well as address rising national rates of congenital syphilis.
Assuntos
Infecções por HIV/transmissão , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Complicações Infecciosas na Gravidez , Serviços Preventivos de Saúde/organização & administração , Brasil/epidemiologia , Estudos de Casos e Controles , Feminino , Infecções por HIV/epidemiologia , Humanos , Lactente , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Gravidez , Avaliação de Programas e Projetos de Saúde , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND AND AIM: Upper GI endoscopy (UGE) is essential for the diagnosis of gastrointestinal diseases. Mucus and bubbles may decrease mucosal visibility. The use of mucolytics could improve visualization. Our aim was to determine whether premedication with simethicone or simethicone plus N-acetylcysteine is effective in improving visibility during UGE. METHODS: This was a randomized, double-blinded, placebo-controlled trial with 2 control groups: no intervention and water 100 mL (W); and 3 intervention groups: simethicone 200 mg (S); S + N-acetylcysteine (NAC) 500 mg (S+NAC500); and S + NAC 1000 mg (S+NAC1000). The solution was ingested 20 minutes before UGE. Gastric visibility was evaluated in 4 segments with a previously described scale. A score of less than 7 points was defined as adequate visibility (AV). Water volume was used to improve visibility, and adverse reactions were evaluated as a secondary outcome. Multiple group comparison was performed using non-parametric one-way analysis of variance (ANOVA). RESULTS: Two hundred thirty patients were included in the study, 68% female, mean age 49 years. The most common indication for UGE was epigastric pain/dyspepsia (33%). AV was more frequent in the S+NAC500 and S+NAC1000 groups (65% and 67%) compared with no intervention (44%, P = .044) and water (41%, P = .022). The gastric total visibility scale (TVS) was significantly better in the S+NAC500 and S+NAC1000 groups compared with water (P = .03 and P = .008). Simethicone was not different from no intervention and water. S+NAC1000 required less water volume to improve visibility. No adverse reactions from the study drugs were observed. CONCLUSIONS: Premedication with S+NAC500 and S+NAC1000 improves visibility during UGE. The use of simethicone did not show improvements in gastric visibility. TVS was worse in patients using water alone. (Clinical trial registration number: NCT 01653171.).
Assuntos
Acetilcisteína/administração & dosagem , Antiespumantes/administração & dosagem , Endoscopia Gastrointestinal/métodos , Expectorantes/administração & dosagem , Mucosa Gástrica/diagnóstico por imagem , Simeticone/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gastropatias/diagnóstico por imagem , Água/administração & dosagemRESUMO
Introducción: La portación nasal de Staphylococcus aureus (SA) en individuos sanos constituye una fuente potencial de infección. La prevalencia de infecciones por SA adquiridas en la comunidad ha aumentado entre los niños sanos. Aunque la epidemiología de la colonización e infección por SA en otros países se ha estudiado ampliamente, los datos son limitados en el Paraguay. Objetivos: Determinar la prevalencia de la portación nasal por SA y su susceptibilidad antimicrobiana en una población de escolares sanos en Asunción, y evaluar factores de riesgo asociados a la colonización. Material y métodos: Estudio multicéntrico, prospectivo, descriptivo y analítico, sobre la colonización nasal por SA en niños de 5 a 16 años, durante el periodo comprendido entre junio y julio del 2016. Previa autorización de los padres y la escuela, se recogieron datos demográficos y factores de riesgo para la colonización. La determinación de SA se realizó mediante muestras de hisopado de las narinas de los niños. Se realizaron pruebas de susceptibilidad antimicrobiana en Agar Mueller y la sensibilidad a la vancomicina se realizó mediante tiras de E-Test®. Los datos fueron registrados en planillas Excel y analizados con el software R v.3.4.2 Resultados: 299 niños fueron incluidos en el estudio. De estos, 58%(173) eran mujeres con una media de edad de 10,6 (±2,5) años. El 79,9% procedía de Asunción y vivía con una media de 5,1 (±1,8) habitantes en el domicilio. Se determinó la presencia de SA en el 30,8% (92/299) de los niños. El 63% de los niños refirió algún factor de riesgo para la colonización por SA. Se objetivo que el antecedente de una enfermedad previa OR=1,92 (95%IC 0,88-4,28), el uso de antibióticos previos OR=1,51 (95%IC 0,89-2,55), la convivencia con mascotas OR=1,42(95%IC 0,81-2,50) y los tratamientos crónicos OR=1,20 (95%IC 0,55-2,61) fueron las variables asociadas a un mayor riesgo de presentar colonización por SA. Conclusión: En el presente estudio se objetivó que el 30,8% de los niños incluidos en el estudio presentaba colonización por SA y que los factores asociados a un mayor riesgo de colonización han sido el antecedente de una enfermedad previa, el uso de antibióticos, la convivencia con mascotas y los tratamientos crónicos.
Introduction: Staphylococcus aureus (SA) nasal carriage in healthy individuals is a potential source of infection. The prevalence of SA infections acquired in the community has increased among healthy children. Although the epidemiology of colonization and infection by SA in other countries has been studied extensively, data are limited in Paraguay. Objectives: To determine the prevalence of nasal carriage by SA and its antimicrobial susceptibility in a population of healthy schoolchildren in Asunción, and to evaluate risk factors associated with colonization. Material and methods: This was a multicenter, prospective, descriptive and analytical study on nasal colonization by SA in children aged 5 to 16 years between June and July 2016. After obtaining authorization from parents and the school, we collected data on demographics and on risk factors for colonization. The SA colonization determination was made by swabbing samples from the children's nostrils. Antimicrobial susceptibility tests were performed on Mueller Agar and the sensitivity to vancomycin was made using E-Test® strips. The data were recorded in Excel spreadsheets and analyzed with the R v.3.4.2 software. Results: 299 children were enrolled in the study. Of these, 58% (173) were female with an average age of 10.6 (± 2.5) years. 79.9% came from Asunción and lived with an average of 5.1 (± 1.8) inhabitants at home. The presence of SA was detected in 30.8% (92/299) of the children. 63% of children reported some risk factor for colonization by SA. We found that a history of a previous disease OR = 1.92 (95% CI 0.88-4.28), the use of previous antibiotics OR = 1.51 (95% CI 0.89-2.55), cohabitation with pets OR = 1.42 (95% CI 0.81-2.50) and chronic treatments OR = 1.20 (95% CI 0.55-2.61) were the variables associated with an increased risk for colonization by SA. Conclusion: In the present study it was found that 30.8% of the children enrolled in the study were colonized by SA and that factors associated with an increased risk of colonization were a history of a previous disease, the use of antibiotics, coexistence with pets and chronic treatments.
RESUMO
El carcinoma epidermoide del hueso temporal es una neoplasia derivada de células epidérmicas del estrato espinoso, y que dado su baja incidencia, y presentación clínica similar a un cuadro de otitis media crónica colesteatomatosa, su diagnóstico es habitualmente tardío. El estudio del carcinoma epidermoide del hueso temporal se realiza con tomografía computarizada, la que evidencia erosión ósea. Sin embargo, existen distintos diagnósticos diferenciales, tanto malignos como benignos, que pueden provocar hallazgos similares en la tomografía computarizada. La resonancia magnética (RM) es un método de exploración de gran valor complementario para el estudio del carcinoma de oído medio. La RM con secuencia de difusión HASTE ha surgido como herramienta de estudio en patología de hueso temporal, tales como colesteatomas y teratomas de oído medio, pese a esto, no existen reportes en la literatura de la presentación imagenológica del carcinoma epidermoide de hueso temporal utilizando este método. En este artículo se presenta un caso clínico de una paciente con carcinoma epidermoide de oído medio, cuyo estudio preoperatorio incluyó RM-HASTE. Aun cuando se requiere un mayor número de casos para establecer el patrón imagenológico, se concluye que esta técnica es de utilidad para diferenciar este tumor de otitis media crónica colesteatomatosa.
Squamous cell carcinoma of the temporal bone (SCC) is a malignancy originated from epidermis spinous cells. Its low incidence and similar presentation to cholesteatomas, contributes to its late diagnosis. The most widely used study for this tumor is computed tomography (CT), which mainly evidences erosion of the temporal bone. There are several other diagnoses, malignant and benign, that could provoke similar findings at the CT. Magnetic resonance imaging (MRI) is a method of great value to study SCC. MRI with HASTE diffusion sequence has recently emerged as an important tool in the study of temporal bone pathologies, such as cholesteatoma and middle ear teratoma, despite this, there are no reports in the literature of the imaging presentation of SCC using this method. This article presents a clinical case of a patient with SCC, in whose preoperative study was performed HASTE-MRI. Although a larger number of cases are required to establish an imaging pattern, it is concluded that this technique is useful to differentiate this tumor from middle ear cholesteatomas.