El difícil camino al diagnóstico del paciente con atrofia muscular espinal / The difficult path to diagnosis of the patient with spinal muscular atrophy

Introducción. Con las nuevas terapias, el diagnóstico temprano de la atrofia muscular espinal (AME) es esencial. El objetivo de este estudio es analizar los distintos componentes que influyen en el retraso diagnóstico. Población y métodos. Se incluyeron pacientes con un diagnóstico molecular de AME tipo I, II y III. Se estudiaron varios parámetros, como la edad al momento de la aparición del primer signo, qué signo fue y el intervalo entre este y el diagnóstico confirmado. Neurólogos especialistas realizaron entrevistas que se complementaron con la revisión de historias clínicas cuando fue necesario. Resultados. Se entrevistaron 112 pacientes. AME I n = 40, AME II n = 48, AME III n = 24. La mediana de edad en meses al momento del reporte del primer signo fue AME I: 1,5 (R 0-7), AME II: 9 (R 2-20), AME III: 18 (R 8-180). Los primeros signos fueron reconocidos por los padres en el 75 % al 85 % de las veces en todos los subtipos. La mediana del tiempo transcurrido entre el primer signo y la primera consulta médica fue menor a un mes en los tres tipos. La mediana de tiempo transcurrido en meses entre el primer signo y el diagnóstico molecular confirmado fue en AME I: 2 (R 0-11), en AME II: 10 (3-46) y en AME III: 31,5 (R 4-288). Conclusiones. Existe un significativo retraso en el diagnóstico de la AME relacionado fundamentalmente a la falta de sospecha clínica. La demora es menor en AME I y mayor en AME III. Otros factores incluyen deficiencias en el sistema de salud.

Introduction. News treatments, make early diagnosis of spinal muscular atrophy (SMA) critical. The objective of this study is to analyze the different factors that influence delay in diagnosis. Population and methods. Patients with a molecular diagnosis of types I, II, and III SMA were included. Several parameters were studied, such as age at onset of first sign, what sign it was, and the time from recognition of first sign to confirmed diagnosis. Neurologists specialized in SMA conducted interviews, supported by the review of medical records when deemed necessary. Results. A total of 112 patients were interviewed. SMA I n = 40, SMA II n = 48, SMA III n = 24. The median age in months at the time of reporting the first sign was SMA I: 1.5 (R: 0­7), SMA II: 9 (R: 2­20), SMA III: 18 (R: 8­180). In all subtypes, first signs were identified by parents from 75% to 85% of the times. The median time from first sign to first medical consultation was less than a month in all 3 types. The median time in months, from first sign to confirmed molecular diagnosis in SMA I was: 2 (R: 0­11), in SMA II: 10 (R: 3­46), in SMA III: 31.5 (R: 4­288). Conclusions. There is a significant delay in SMA diagnosis mainly related to the absence of clinical suspicion. The delay is shorter in SMA I and longer in SMA III. Other factors include deficiencies in the health care system.

Health-related quality of life in adults with juvenile idiopathic arthritis / Calidad de vida relacionada con la salud en pacientes adultos con artritis idiopática juvenil

ABSTRACT Background: Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in the paediatric age. It is estimated that between 30-60% of adults patients persist with active disease, which leads to sequelae and complications as well as a decrease functional capacity and reduced quality of life. Objectives: To evaluate the health-related quality of life in adult patients diagnosed with juvenile idiopathic arthritis. Methodology: A cross-sectional study was performed, using a search for adult patients diagnosed with JIA between 1996 and 2018. Clinical records were reviewed during the paediatric age, and clinical parameters were evaluated for activity (JADASc-71), and joint (JADI-A) and extra-articular (JADI-E) damage, functional capacity (HAQ), and quality of life (SF-36). Relationships were determined by non-conditional logistic regression. Results: A total of 69 patients were included. The most frequent subtype of JIA was enthesitis-related arthritis (ERA) (33%). Active disease was observed in 33%. Polyarticular JIA RF (+) was associated with active disease (P = .007), high values of JADASc-71 (P = .003), and HAQ (P = .001). Age of onset after 5 years reduced risk of joint damage (OR = 0.16) and extra-articular damage (OR = 0.03). Poor therapeutic adherence was associated with joint damage (P = .00) and JADASc-71 (P = .004). A high score of JADI-E was associated with functional dis-ability (OR = 5.75). Joint damage (P = .003) and extra-articular damage (P = .024), and functional disability (OR = 7.05) were associated with low values in the SF-36. Conclusions: JIA is not a disease limited to the paediatric age. Persistence of active disease, joint, and extra-articular damage are associated with functional disability and a decrease in H-RQoL.

RESUMEN Introducción: La artritis idiopática juvenil (AIJ) permanece activa en el 30-60% de los pacientes adultos, conduciendo a complicaciones articulares, extraarticulares, disminución en la capacidad funcional y reducción en la calidad de vida. Objetivos: Evaluar la calidad de vida relacionada con la salud en pacientes adultos con diagnóstico de AIJ. Metodología: Estudio corte transversal; se realizó una búsqueda de pacientes adultos con diagnóstico de AIJ entre 1996 y 2018. Se revisaron historias clínicas durante la edad pediátrica y se evaluaron parámetros clínicos para actividad (JADASc-71), daño articular (JADI-A) y extraarticular (JADI-E), capacidad funcional (HAQ) y calidad de vida (SF-36). Asociaciones determinadas por regresión logística no condicional. Resultados: Se incluyó a 69 pacientes. El subtipo de AIJ más frecuente fue la artritis relacionada con la entesitis (ARE) (33%). El 33% de los pacientes tenían enfermedad activa. La AIJ poliarticular FR positivo se asoció a enfermedad persistentemente activa (p = 0,007), altos valores del JADASc-71 (p = 0,003) y HAQ (p = 0,001). La edad de inicio posterior a 5 años redujo el riesgo de daño articular (OR = 0,16) y extraarticular (OR = 0,03). La mala adherencia terapéutica se asoció a daño articular (p = 0,00) y JADASc-71 (p = 0,004). La alta puntuación del JADI-E se asoció a discapacidad funcional (OR = 5,75). El daño articular (p = 0,003) y extraarticular (p = 0,024) y discapacidad funcional (OR = 7,05) se asociaron a bajos valores en SF-36. Conclusiones: La AIJ no es una enfermedad limitada a edad pediátrica. La persistencia de enfermedad activa y el daño articular y extraarticular se asocian a discapacidad funcional y disminución en la calidad de vida relacionada con la salud.

The natural history of solitary post-nephrectomy kidney in a pediatric population

ABSTRACT Introduction: Children with a solitary post-nephrectomy kidney (SNK) are at potential risk of developing kidney disease later in life. In response to the global decline in the number of nephrons, adaptive mechanisms lead to renal injury. The aim of this study was to determine the prevalence and time of onset of high blood pressure (HBP), proteinuria, glomerular filtration rate (GFR) disruption and renal tubular acidosis (RTA) in children with SNK. Materials and methods: After obtaining the approval from our institution's ethics committee, we reviewed the medical records of patients under 18 years of age who underwent unilateral nephrectomy between January 2005 and December 2015 in three university hospitals. Results: We identified 43 patients, 35 (81.4%) cases of unilateral nephrectomy (UNP) were due to a non-oncologic pathology and Wilm's tumor was identified in 8 (18.6%) cases. In patients with non-oncologic disease, 9.3% developed de novo hypertension, with an average time of onset of 7.1 years, 25% developed proteinuria de novo, with an average time of onset of 2.2 years. For GFR, 21.8% presented deterioration of the GFR in an average time of 3.4 years. Ten (43.5%) patients developed some type of de novo renal injury after UNP. Patients with oncologic disease developed the conditions slowly and none of them developed proteinuria. Conclusions: Taking into account the high rate of long term postoperative renal injury, it can be considered that nephrectomy does not prevent this disease. The follow-up of children with SNK requires a multidisciplinary approach and long-term surveillance to detect renal injury.

Employment status of people diagnosed with multiple sclerosis in Brazil / Situação de empregabilidade em pessoas com esclerose múltipla no Brasil

ABSTRACT Objective: To describe the employment status of Brazilians with multiple sclerosis (MS). Methods: Analysis of a cross-sectional online survey including questions on demographic and occupational status at the time of diagnosis and survey completion, and time from the first symptom to diagnosis. Results: Of those who answered the survey, 804 Brazilians with MS were included. Median age of onset and current age were 28.3 and 36.2 years; median time to diagnosis and disease duration were 2.7 and 7.9 years; 67% held a university degree and 29% finished high school; 94% had a paid occupation contributing to the family income at least once in their lives, 77% were employed at the time of diagnosis but only 59% were employed at the time of survey. Longer disease duration, longer time to diagnosis and younger age at the first symptom, were identified as factors correlated with being unemployed. Conclusions: The rate of unemployment doubled after the first symptoms of MS, and only 59% of highly-educated people with MS in their productive years were employed. The longer time to diagnosis may imply treatment delay, and strategies focusing on early diagnosis and adequate treatment may favor employment retention and reduce disability related costs, such as social benefits and pension fund use.

RESUMO Objetivo: Descrever o estado de empregabilidade de uma amostra brasileira de pessoas com esclerose múltipla (EM). Métodos: Estudo transversal incluindo informações demográficas e ocupacionais no momento do diagnóstico e atual, e o tempo do primeiro sintoma ao diagnóstico. Resultados: Foram incluídos 804 pacientes com EM, com mediana de idade de início dos sintomas e atual de 28,3 e 36,2 anos; tempo mediano para diagnóstico e duração da doença de 2,7 e 7,9 anos. Desta amostra, 67% possuíam diploma universitário e 29% terminaram o ensino médio. No total, 94% tiveram uma ocupação remunerada pelo menos uma vez na vida, 77% estavam empregados no diagnóstico, mas apenas 59% estavam empregados no momento da pesquisa. Maior duração de doença, maior tempo para o diagnóstico e menor idade no 1° sintoma foram os fatores relacionados ao desemprego. Conclusões: A taxa de desemprego dobra após os primeiros sintomas da EM, e apenas 59% das pessoas com alto nível educacional com EM em seus anos produtivos estão empregados. Maior tempo para o diagnóstico pode implicar atraso no tratamento, e estratégias com foco no diagnóstico precoce e tratamento adequado podem favorecer a retenção de emprego e reduzir os custos relacionados à doença, como benefícios sociais e uso de fundos de pensão.

Experimentation with tobacco during adolescence as a factor influencing treatment of smoking in adulthood. A retrospective cohort

ABSTRACT BACKGROUND: There are still few studies on predictors of smoking cessation in Brazilian samples. Experimentation with tobacco during adolescence (ETA) may be one of the important predictors. OBJECTIVE: This study aimed, within the context of a treatment-seeking group of subjects, to test the hypothesis that ETA negatively affects the outcome of smoking cessation during adulthood. DESIGN AND SETTING: Retrospective (historic) cohort study conducted at a psychosocial care center in São Paulo, Brazil, between 2007 and 2010. METHODS: Data on sociodemographics, smoking and medical profiles were obtained through self-report questionnaires that were completed at the baseline and at any follow-up appointment. Logistic regression models were constructed to describe factors associated with the outcome of smoking cessation, measured according to the self-reported four-week success rate among 367 outpatient smokers. RESULTS: ETA was found to be associated with not quitting smoking through the treatment (odds ratio = 0.57; 95% confidence interval = 0.33-0.96; P < 0.05), even after adjustment for dependence level, sociodemographics, nicotine patch use and number of years of smoking. CONCLUSIONS: Early exposure to nicotine may lead to higher risk of continuing smoking after treatment, in adulthood.

Evaluación de la dependencia física y psicológica al tabaco en fumadores mexicanos adultos, Encodat 2016 / Evaluation of physical and psychological dependence in Mexican adult smokers, Encodat 2016

Resumen: Objetivo: Evaluar la dependencia física y psicológica de los fumadores mexicanos y su asociación con factores físicos, psicológicos y sociales. Material y métodos: A partir de la Encuesta Nacional de Consumo de Drogas, Alcohol y Tabaco 2016 (n=7 331), se analizó la escala de dependencia física a la nicotina de Fagerström (FTND) y la escala corta de dependencia psicológica al tabaco (TAPDSc). Se realizaron análisis bivariados y regresiones logísticas ordinales generalizadas para evaluar los factores asociados. Resultados: 82.3% de fumadores diarios y 98.8% de ocasionales reportaron dependencia física leve, mientras que 47.9 y 37.9%, respectivamente, presentaron dependencia psicológica moderada. La edad de inicio temprana de consumo de tabaco, uso de drogas, consumo alto de alcohol y malestar emocional se asociaron con niveles altos de dependencia psicológica en todos los fumadores. Conclusión: El uso exclusivo de FNTD no permite evaluar adecuadamente a los fumadores mexicanos. La dependencia física y psicológica al tabaco debe ser diagnosticada con escalas independientes y validadas en esta población.

Abstract: Objective: To evaluate the physical and psychological dependence to tobacco of Mexican smokers and its association with physical, psychological and social factors. Materials and methods: The 2016 National Alcohol and Tobacco Drug Consumption Survey (n=7 331) was analyzed using the Fagerström nicotine physical dependence scale (FTND) and the short scale of psychological dependence on tobacco (TAPDSc). Bivariate analyzes and generalized ordinal logistic regressions were performed to evaluate the associated factors. Results: 82.3% of daily smokers and 98.8% of occasional smokers reported mild physical dependence, while 47.9 and 37.9% respectively reported moderate psychological dependence. The age of initiation of tobacco use, drug use, high alcohol consumption and high emotional distress were associated with high levels of psychological dependence in all smokers. Conclusion: The exclusive use of FTND does not allow to adequately evaluate Mexican smokers. The physical and psychological dependence on tobacco should be assessed with independent and validated scales in this population.

The prevalence of bruxism and related factors in patients with multiple sclerosis: a comparative study / A prevalência do bruxismo e fatores relacionados em pacientes com esclerose múltipla: um estudo comparativo

ABSTRACT Objective: To determine the prevalence of bruxism and related factors in patients with multiple sclerosis (MS). Methods: Diagnosed with relapsing-remitting MS under the 2010-revised McDonald diagnostic criteria, 182 patients without MS exacerbations during the previous three months were included in the patient group, and 145 healthy individuals made up the control group in the study. Demographic data of the participants in both groups were determined. In the patient and control groups, the diagnosis of definite bruxism was made using the International Classification of Sleep Disorders (Diagnosis and Coding Manual, Second Edition). Results: Bruxism was found in 29.7% (n = 54) of the patients and in 12.4% (n = 18) of the controls, and the difference was statistically significant (p < 0.001). Of all patients, the onset of bruxism was found in 70.4% (n = 38) after the diagnosis and in 29.6% (n = 169) prior to the diagnosis of MS. Compared with those without bruxism, the mean age (p = 0.031) and the score of the Expanded Disability Status Scale (p = 0.001) were also significantly higher among MS patients with bruxism. Between MS patients with and without bruxism, no significant differences were found in terms of sex, marital status, educational status, employment, cigarette smoking, total number of exacerbations, number of exacerbations within the previous year, and drugs used. Conclusions: The frequency of bruxism was found to be higher in the patients with MS than in the controls. Bruxism is associated with age and the Expanded Disability Status Scale score in MS patients.

RESUMO Objetivo: Neste estudo, pretendeu-se determinar a prevalência de bruxismo e fatores relacionados em pacientes com esclerose múltipla (EM). Métodos: Diagnosticados com EM remitente recidivante sob os critérios de McDonald Diagnostic revisados em 2010, 182 pacientes sem ataques de EM durante os últimos três meses foram incluídos no grupo de pacientes, e 145 indivíduos saudáveis constituíram o grupo de controle no estudo. Os dados demográficos dos participantes dos dois grupos foram determinados. Nos grupos de pacientes e controle, o diagnóstico de bruxismo definitivo foi feito usando a Classificação Internacional de Distúrbios do Sono (1) (Manual de Diagnóstico e Codificação Segunda Edição). Resultados: O bruxismo foi detectado em 29,7% (n = 54) dos pacientes e observado dentro de 12,4% (n = 18) dos controles, e a diferença foi estatisticamente significante (p <0,001). De todos os pacientes, o tempo inicial de bruxismo foi encontrado em 70,4% (n = 38) após o diagnóstico e em 29,6% (n = 169) antes do diagnóstico. Em comparação com aqueles sem bruxismo, os níveis de idade média (p = 0,031) e o escore da Escala de Status de Incapacidade Expandida (p = 0,001) também foram significativamente maiores entre os pacientes com esclerose múltipla com bruxismo. Entre os pacientes com esclerose múltipla com e sem bruxismo, não foi encontrada diferença significativa em termos de sexo, estado civil, status educacional, emprego, tabagismo, número total de ataques, número de ataques no último ano e medicamentos utilizados. Conclusões: A freqüência de bruxismo foi maior em pacientes com esclerose múltipla do que nos controles. O bruxismo está associado à idade e ao escore da Escala de Status de Incapacidade Expandida (EDSS) em pacientes com EM.

GBA mutations p.N370S and p. L444P are associated with Parkinson's disease in patients from Northern Brazil / Mutações p.N370S e p. L444P no gene GBA estão associadas com doença de Parkinson em pacientes do norte do Brasil

ABSTRACT Mutations of the GBA gene have been reported in patients with Parkinson's disease (PD) from a number of different countries, including Brazil. In order to confirm this pattern in a sample of PD patients from northern Brazil, we conducted a case-control study of the occurrence of the two most common mutations of the GBA gene (c.1226A>G; p.N370S and c.1448T>C; p.L444P) in a group of 81 PD patients and 81 control individuals, using PCR-RFLP, confirmed by the direct sequencing of the PCR products. In the patient group, three patients (3.7%) were heterozygous for the GBA c.1226A>G; p.N370S mutation, and three (3.7%) for GBA c.1448T>C; p.L444P Neither mutation was detected in the control group (p =0.0284). Patients with the c.1448T>C; p.L444P mutation showed a tendency to have an earlier disease onset, but a larger sample number is required to confirm this observation. Our results suggest an association between the GBA c.1226A>G; p.N370S and c.1448T>C; p.L444P mutations and the development of PD in the population of patients from the Northern Brazil.

RESUMO Mutações no gene GBA têm sido reportadas em pacientes com doença de Parkinson (DP) em diferentes países, incluindo o Brasil. Com o objetivo de confirmar esse padrão em uma amostra de pacientes com DP provenientes do Norte brasileiro, foi conduzindo esse estudo caso-controle investigando a frequência das duas mutações mais comuns do gene GBA (c.1226A>G; p.N370S e c.1448T>C; p.L444P) em um grupo de 81 pacientes com DP e 81 controles, usando PCR-RFLP e confirmado pelo sequenciamento direto de produtos de PCR. No grupo experimental, três pacientes (3,7%) foram heterozigotos para a mutação c.1226A>G; p.N370S e três (3,7%), para a mutação c.1448T>C; p.L444P Nenhuma das duas mutações foi detectada no grupo controle (p =0,0284). Pacientes com a mutação c.1448T>C; p.L444P demonstraram uma tendência a apresentar os sintomas mais precocemente, porém um número amostrai maior é necessário para confirmar essa observação. Nossos resultados sugerem uma associação entre essas duas mutações no gene GBA e o desenvolvimento de DP na população de pacientes do norte Brasileiro.

Obsessive-compulsive symptoms in children with first degree relatives diagnosed with obsessive-compulsive disorder

Objective: A first-degree relative affected by obsessive-compulsive disorder (OCD) and obsessive-compulsive symptoms (OCS) in childhood is an important risk factor for developing the disorder in adulthood. The relationship between a family history of OCD and the presence of OCS and its correlates in childhood is not well established. Methods: A total of 66 children whose parents or siblings have been diagnosed with OCD were assessed for the presence of OCS and clinical correlates. Results: Three children (4.5%) were reported to have received an OCD diagnosis and another 26 (39.4%) were identified as having OCS. Children with OCS had higher rates of coercive behavior and came from families with lower socioeconomic status. Contamination/cleaning dimension symptoms in the proband were associated with OCS in the assessed children. Conclusion: OCS are frequent among family members of individuals with OCD and are associated with socioeconomic status, coercive behaviors and proband contamination/cleaning symptoms. Future longitudinal studies should test the risk of developing OCD in association with these characteristics.

Avaliação funcional em indivíduos com doença de Huntington: uma série de casos / Functional evaluation in Huntington's disease: a series of cases

A doença de Huntington (DH) é uma desordem neurodegenerativa, que cursa com distúrbios motores, cognitivos e comportamentais que contribuem para o comprometimento da funcionalidade. Este estudo investigou o grau de funcionalidade e acometimento de indivíduos portadores da DH, com o Índice de Barthel Modificado (IBM) e por meio do Disease Burden Score (DBS). As variáveis analisadas de cada indivíduo foram: a idade atual, o gênero, a idade de início da doença e o número das repetições CAG (gene HTT). Seis indivíduos foram avaliados, três do sexo masculino 63,6 anos (±10,9) e três do sexo feminino 58,3 anos (±14,2) com o diagnóstico genético positivo para DH provenientes do município de Ervália/MG. O sexo feminino apresentou a idade de início menor comparado ao sexo masculino, com média de 38,3 anos (±8,9) e 46,6 anos (±7,6), respectivamente. O valor médio do número de repetições CAG no sexo feminino foi de 46,3 (±4,1) e no sexo masculino, 42,33 (±1,5). O grau de desempenho funcional determinado pelo IBM foi de 9,3 (±1,1) para o sexo feminino, com dependência total, e para o sexo masculino, 36 (±4,3), com dependência severa. O valor médio obtido pelo DBS no sexo feminino foi de 596,8 (±101,9), com maior grau de acometimento da doença comparado ao sexo masculino com 425,1 (±39,2). O grupo de mulheres com DH apresentou início dos sintomas mais cedo com maior número de expansões CAG quando comparado ao grupo masculino. Todos os pacientes apresentaram dependência total em relação à execução das atividades de vida diária. Sugere-se que pesquisas futuras sejam realizadas com maior número de indivíduos afetados pela DH para que os resultados observados sejam confirmados.

Huntington's disease (HD) is a neurodegenerative disorder, presenting with motor, cognitive and behavioral impairments that contribute to the decrease of the functional performance. This study investigated the degree of functionality and impairment of individuals with HD using the Modified Barthel Index (MBI) and the Disease Burden Score (DBS). The following variables were investigated : the age of onset, the gender, the current age and the number of CAG (HTT gene) repeats. Six HD patients from the municipality of Ervália-MG, three males 63.6 years old (±10.9) and three females 58.3 years old (±14.2), who had a positive genetic diagnosis for HD, were investigated. The female group had the lowest age of onset with an average of 38.3 years (±8.9), compared to the male group, with 46.6 years (±7.6). The mean of the number of CAG repeats in the female gender was 46.3 (±4.1) and in the male, 42.33 (±1.5). The degree of functional performance assessed by IBM was 9.3 (±1.1) for the female group, with total dependence, and for the male group, 36 (±4.3), with severe dependence. The mean of DBS value in the female group was 596.8 (±101.9) with a higher degree of disease involvement compared to the male group 425.1 (±39.2). The group of women with HD showed earlier onset of symptoms with a greater number of CAG repeats when compared to the male group. All patients presented total dependence on daily living activities. We strongly suggest further research involving a larger group of individuals affected by HD for statistical validation.

Depressive symptoms, emotional support and activities of daily living disability onset: 15-year follow-up of the Bambuí (Brazil) Cohort Study of Aging / Sintomas depressivos, apoio emocional e início do comprometimento das atividades da vida diária: seguimento de 15 anos do Estudo de Coorte de Idosos de Bambuí, Minas Gerais, Brasil / Síntomas depresivos, apoyo emocional y actividades del día a día, conviviendo con la aparición de una discapacidad: seguimiento durante 15 años del Estudio de Cohorte Envejecimiento de Bambuí (Brasil)

Psychosocial factors appear to be associated with increased risk of disability in later life. However, there is a lack of evidence based on long-term longitudinal data from Western low-middle income countries. We investigated whether psychosocial factors at baseline predict new-onset disability in long term in a population-based cohort of older Brazilians adults. We used 15-year follow-up data from 1,014 participants aged 60 years and older of the Bambuí (Brazil) Cohort Study of Aging. Limitations on activities of daily living (ADL) were measured annually, comprising 9,252 measures. Psychosocial factors included depressive symptoms, social support and social network. Potential covariates included sociodemographic characteristics, lifestyle, cognitive function and a physical health score based on 10 self-reported and objectively measured medical conditions. Statistical analysis was based on competitive-risk framework, having death as the competing risk event. Baseline depressive symptoms and emotional support from the closest person were both associated with future ADL disability, independently of potential covariates wide range. The findings showed a clear graded association, in that the risk gradually increased from low emotional support alone (sub-hazard ratio - SHR = 1.11; 95%CI: 1.01; 1.45) to depressive symptoms alone (SHR = 1.52; 95%CI: 1.13; 2.01) and then to both factors combined (SHR = 1.61; 95%CI: 1.18; 2.18). Marital status and social network size were not associated with incident disability. In a population of older Brazilian adults, lower emotional support and depressive symptoms have independent predictive value for subsequent disability in very long term.

Fatores psicossociais parecem estar associados a um aumento do risco de incapacidade em idosos. Entretanto, faltam evidências baseadas em dados longitudinais de longo prazo em países ocidentais de renda baixa e média. Investigamos se os fatores psicossociais presentes na linha de base predizem a incapacidade incidente no longo prazo em uma coorte populacional de idosos brasileiros. Usamos dados do seguimento de 15 anos de 1.014 participantes com 60 anos de idade ou mais do Estudo de Coorte de Idosos de Bambuí, Minas Gerais, Brasil. Foram medidas anualmente as limitações nas atividades de vida diária (AVD), totalizando 9.252 mensurações. Os fatores psicossociais incluíram sintomas depressivos, apoio emocional e rede social. As variáveis independentes incluíram características sociodemográficas, estilo de vida, função cognitiva e uma escala de saúde física com dez condições clínicas autorrelatadas e medidas objetivas. A análise estatística foi baseada em um modelo de risco competitivo, tendo o óbito como evento de risco competitivo. Os sintomas depressivos na linha de base e o apoio emocional da pessoa mais próxima estiveram associados à incapacidade futura nas AVD, independentemente da grande amplitude das variáveis independentes. Os achados mostraram um claro gradiente de associação, onde o risco aumentou progressivamente desde o baixo apoio emocional isoladamente (sub-hazard ratio - SHR = 1,11; IC95%: 1,01; 1,45) para sintomas depressivos isoladamente (SHR = 1,52; IC95%: 1,13; 2,01) até a combinação de ambos os fatores (SHR = 1,61; IC95%: 1,18; 2,18). O estado civil e o tamanho da rede social não mostraram associação com a mortalidade incidente. Em uma população de idosos brasileiros, o apoio emocional baixo e sintomas depressivos apresentam valores preditivos independentes em relação à incapacidade subsequente no prazo muito longo.

Los factores psicosociales parecen que estaban asociados con un aumento del riesgo de sufrir discapacidad más adelante a lo largo de la vida. Sin embargo, existe una falta de evidencias en los datos a largo plazo de carácter longitudinal, procedentes de países occidentales con una renta medio-baja. Investigamos si los factores psicosociales como base de referencia predicen un surgimiento de discapacidad a largo plazo en una cohorte de población, basada en adultos ancianos brasileños. Se realizó un seguimiento durante 15 años con datos de 1.014 participantes con 60 años y de mayor edad en el Estudio de Cohorte Envejecimiento de Bambuí (Brasil). Las limitaciones en las actividades de la vida diaria (ADL por sus siglas en inglés) fueron medidas anualmente, comprendiendo 9.252 medidas. Se trabajó con factores psicosociales, incluidos síntomas depresivos, apoyo social y tejido social. Las covariables potenciales incluyeron características sociodemográficas, estilo de vida, función cognitiva y un marcador de salud física, basado en 10 condiciones médicas autoinformadas y medidas objetivamente. El análisis estadístico estaba basado en un marco de riesgo competitivo, considerando la muerte como riesgo competitivo. Las bases de referencia de los síntomas depresivos y el apoyo emocional de la persona más cercana estuvieron asociadas con una futura discapacidad ADL, independientemente del extenso rango de potenciales covariables. Los resultados muestran un clara asociación graduada, en la que el riesgo gradualmente aumentó desde un bajo apoyo emocional solo (sub-hazard ratio - SHR = 1,11; IC95%: 1,01; 1,45) para síntomas depresivos sólo (SHR = 1.52; IC95%: 1,13; 2,01) y luego para ambos factores combinados (SHR = 1,61; IC95%: 1.18; 2.18). El estado marital y el tamaño del tejido social no estuvieron asociados con la incidencia de discapacidad. En una población de adultos mayores brasileños, un apoyo emocional más bajo y síntomas depresivos poseen un valor predictivo independiente para una consecuente discapacidad a muy largo plazo.

Hereditary angioedema with C1 inhibitor (C1-INH) deficit: the strength of recognition (51 cases)

Hereditary angioedema (HAE) is a rare autosomal dominant disease due to C1 esterase inhibitor deficiency (C1-INH). The disease is characterized by subcutaneous and submucosal edema in the absence of urticaria due to the accumulation of bradykinin. This descriptive study aimed to evaluate the clinical characteristics of patients with a confirmed diagnosis of HAE referred to our Outpatient Clinic between December 2009 and November 2017. Fifty-one patients (38 F, 13 M) with a mean age of 32 years (range: 7-70 y) were included. Family history of HAE was reported in 70% (36/51) of the cases; 33/46 patients became symptomatic by 18 years of age. The median time between onset of symptoms and diagnosis was 13 years (3 mo-50 y). The most frequent triggering factors for attacks were stress (74.4%), trauma (56.4%), and hormonal variations (56%). The main symptoms were subcutaneous edema in 93.5% (43/46) of patients, gastrointestinal symptoms in 84.8% (39/46), and obstruction in the upper airways in 34.8% (16/46). Hospitalization occurred in 65.2%, of whom 13.3% had to be transferred to the Intensive Care Unit. Prophylactic treatment was instituted in 87% (40/46) of patients, and 56.5% (26/46) required additional treatment to control attacks. Owing to our data collection over a period of 8 years, a significant number of patients were identified by this HAE reference center. Despite early recognition and prophylactic treatment, a high percentage of patients were hospitalized. HAE is still diagnosed late, reinforcing the need for more reference centers specialized in diagnosis and educational projects for health professionals.

Age at first childbirth and newly diagnosed diabetes among postmenopausal women: a cross-sectional analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) / Idade no primeiro parto e diabetes recentemente diagnosticada em mulheres pós-menopáusicas: uma análise transversal do Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil)

ABSTRACT CONTEXT AND OBJECTIVE: It has been reported that earlier age at first childbirth may increase the risk of adult-onset diabetes among postmenopausal women, a novel finding with important public health implications. To date, however, no known studies have attempted to replicate this finding. We aimed to test the hypothesis that age at first childbirth is associated with the risk of adult-onset diabetes among postmenopausal women. DESIGN AND SETTING: Cross-sectional analysis using baseline data from 2919 middle-aged and elderly postmenopausal women in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). METHODS: Age at first childbirth was determined from self-reporting and newly diagnosed diabetes through a 2-hour 75-g oral glucose tolerance test and/or glycated hemoglobin. Logistic regression was performed to examine associations between age at first childbirth and newly diagnosed diabetes among postmenopausal women. RESULTS: We did not find any association between age at first childbirth and diabetes, either when minimally adjusted for age, race and study center (odds ratio, OR [95% confidence interval, CI]: ≤ 19 years: 1.15 [0.82-1.59], 20-24 years: 0.90 [0.66-1.23] and ≥ 30 years: 0.86 [0.63-1.17] versus 25-29 years; P = 0.36) or when fully adjusted for childhood and adult factors (OR [95% CI]: ≤ 19 years: 0.95 [0.67-1.34], 20-24 years: 0.78 [0.56-1.07] and ≥ 30 years: 0.84 [0.61-1.16] versus 25-29 years; P = 0.40). CONCLUSION: Our current analysis does not support the existence of an association between age at first childbirth and adult-onset diabetes among postmenopausal women, which had been reported previously.

RESUMO CONTEXTO E OBJETIVO: Foi relatado que idade mais precoce no primeiro parto pode aumentar o risco do diabetes de início adulto entre mulheres na menopausa, um novo achado com implicações de saúde pública importantes. Até então, no entanto, nenhum estudo conhecido tentou replicar esta descoberta. Objetivou-se testar a hipótese de que a idade no primeiro parto está associada ao risco de diabetes de início na vida adulta em mulheres pós-menopáusicas. DESENHO DE ESTUDO E LOCAL: Análise transversal utilizando dados de base de 2.919 mulheres pós-menopáusicas de meia-idade e idosas no Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil). MÉTODOS: A idade no primeiro parto foi determinada por autorrelato e diabetes recentemente diagnosticado por um teste de tolerância à glicose oral de 2 horas com 75 g e/ou hemoglobina glicada. A regressão logística foi realizada para examinar associações entre idade no primeiro parto e diabetes recentemente diagnosticada entre mulheres pós-menopáusicas. RESULTADOS: Não encontramos associação entre idade no primeiro parto e diabetes, quando ajustados minimamente para idade, raça e centro de estudo (odds ratio, OR [intervalo de confiança, IC 95%]: ≤ 19 anos: 1,15 [0,82-1,59], 20-24 anos: 0,90 [0,66-1,23], ≥ 30 anos: 0,86 [0,63-1,17] versus 25-29 anos, P = 0,36) ou quando totalmente ajustados para fatores infantis e adultos (OR [IC 95%]: ≤ 19 anos: 0,95 [0,67-1,34], 20-24 anos: 0,78 [0,56-1,07], ≥ 30 anos: 0,84 [0,61-1,16] versus 25-29 anos, P = 0,40). CONCLUSÃO: Nossa análise atual não apoia uma associação entre a idade no primeiro parto e o diabetes de início na vida adulta entre mulheres pós-menopáusicas, como relatado anteriormente.

Characterization of the first symptoms of multiple sclerosis in a Brazilian center: cross-sectional study / Caracterização dos primeiros sintomas de esclerose múltipla em um centro brasileiro: estudo transversal

ABSTRACT CONTEXT AND OBJECTIVE: Multiple sclerosis (MS) is a chronic, immune-mediated and degenerative central nervous system (CNS) disease with well-established diagnostic criteria. Treatment can modify the course of the disease. The objective of this study was to describe the initial symptoms of multiple sclerosis in a Brazilian medical center. DESIGN AND SETTING: Descriptive study, conducted in a Brazilian reference center for multiple sclerosis treatment. METHODS: Data on 299 patients with confirmed diagnoses of MS were included in the study. Their medical files were evaluated and the data were analyzed. RESULTS: The most common symptom involved the cranial nerves (50.83%) and unifocal manifestation was presented by the majority of this population (73.91%). The mean time between the first symptom and the diagnosis was 2.84 years. Unifocal symptoms correlated with longer time taken to establish the diagnosis, with an average of 3.20 years, while for multifocal symptoms the average time taken for the diagnosis was 1.85 years. Unifocal onset was related to greater diagnostic difficulty. CONCLUSIONS: MS is a heterogeneous disease and its initial clinical manifestation is very variable.

RESUMO CONTEXTO E OBJETIVO: A esclerose múltipla (EM) é uma doença crônica do sistema nervoso central (SNC) imunomediada e degenerativa, com critérios diagnósticos bem estabelecidos. O tratamento pode modificar o curso da doença. O objetivo deste estudo foi descrever os sintomas iniciais da esclerose múltipla em um centro médico brasileiro. TIPO DE ESTUDO E LOCAL: Estudo descritivo, conduzido em um centro médico de referência no tratamento de EM no Brasil. MÉTODOS: Foram incluídos no estudo dados de 299 pacientes com diagnóstico confirmado de EM. Seus prontuários foram avaliados e os dados foram analisados. RESULTADOS: O sintoma mais comum encontrado envolveu nervos cranianos (50,83%) e a manifestação unifocal foi apresentada pela maioria da população estudada (73,91%). O tempo médio entre o primeiro sintoma e o diagnóstico foi de 2,84 anos. O sintoma unifocal foi relacionado com maior tempo para o estabelecimento do diagnóstico, com uma média de 3,20 anos; enquanto para os sintomas multifocais, a média foi de 1,85 anos para o diagnóstico. O início unifocal foi relacionado a maior dificuldade de diagnóstico. CONCLUSÕES: EM é uma doença heterogênea e sua manifestação clínica inicial é muito variável.

Idiopathic Musculoskeletal Pain in Indian children-Prevalence and Impact on Daily Routine / Prevalência e impacto nas atividades diárias da dor musculoesquelética idiopática em crianças da Índia

ABSTRACT Objectives: To study the prevalence of idiopathic musculoskeletal pain (IMSP) in school going children and its impact on daily life. Methods: One thousand eighteen apparently healthy school children aged 5–16 years were assessed and analysed for IMSP and its associated problems. Standard tests for significance were applied. Results: One hundred and sixty-five (16.2%) children mostly males (55.2%) reported IMSP. Lower limbs (52.1%) were the most common location of pain. More than 1 year of pain history was present in 15%. Thirty-seven percent children complained of discomfort during walking, 30.9%, had pain during physical exercise, 29.2% had difficulty attending lessons and 4.2% had interference in pursuing hobbies. The children were also further sub grouped into preadolescents and adolescents. There was significant difference in pain duration and duration of each pain episode in the two groups (p = 0.01). A significant number of children (21.2%) with IMSP reported school absenteeism (p < 0.001). A significant number of adolescents had history positive for contact sports (p = 0.001). Sleep disturbances were also reported to be higher in children with IMSP (29% vs. 5.7%, p = 0.001). Other associated problems in children with IMSP found were day time tiredness (51.1%), headache (47.3%) and abdominal pain (24.8%). Conclusions: Prevalence of IMSP in school children aged 5–16 yrs was found to be 16.2% and a significant percentage of these children experience interference with daily activities including school absenteeism.

RESUMO Objetivos: Estudar a prevalência de dor musculoesquelética idiopática (DMEI) em crianças em idade escolar e seu impacto nas atividades diárias. Métodos: Foram avaliadas e analisadas 1.018 crianças em idade escolar aparentemente saudáveis entre cinco e 16 anos quanto à presença de DMEI e seus problemas associados. Foram aplicados os testes de significância padrão. Resultados: Relataram DMEI 165 (16,2%) crianças, em sua maior parte do sexo masculino (55,2%). Os membros inferiores (52,1%) foram a localização mais comum da dor. A história de dor presente havia mais de um ano foi encontrada em 15% das crianças; 37% delas queixaram-se de desconforto durante a caminhada, 30,9%, tinham dor durante o exercício físico, 29,2% tinham dificuldade de frequentar as aulas e 4,2% sofriam interferência na participação em passatempos. As crianças foram ainda subagrupadas em pré-adolescentes e adolescentes. Houve diferença estatisticamente significativa na duração da dor e na duração de cada episódio de dor nos dois grupos (p = 0,01). Uma quantidade significativa de crianças com DMEI (21,2%) relatou absentismo escolar (p < 0,001). Uma quantidade significativa de adolescentes tinha história positiva de prática de esportes de contato (p = 0,001). Os distúrbios do sono também foram relatados como maiores em crianças com DMEI (29% vs. 5,7%, p = 0,001). Outros problemas associados encontrados em crianças com DMEI foram o cansaço durante o dia (51,1%), a cefaleia (47,3%) e a dor abdominal (24,8%). Conclusões: A prevalência de DMEI encontrada em crianças entre cinco e 16 anos foi de 16,2%. Uma percentagem significativa dessas crianças relata interferência nas atividades diárias, incluindo absentismo escolar.

Medición de la ingestión de sodio en la dieta de un grupo de niños entre uno y 18 meses de edad en una consulta pediátrica en Cali, Colombia / Measurement of dietary sodium intake in a group of children from one to 18 months of age in a pediatric service in Cali, Colombia

Resumen Introducción. Las estrías de grasa en la pared arterial pueden aparecer desde el tercer año Resumende vida y se relacionan con factores de riesgo aterogénico, como la hipertensión arterial sistémica y el contenido de sodio en la dieta. En pocos estudios se reporta el consumo de sodio en la dieta debido a la dificultad para la recolección de los datos. Objetivo. Determinar el consumo promedio de sodio en la dieta de niños de uno a 18 meses de edad, mediante una encuesta sobre la dieta a lo largo de tres días. Materiales y métodos. Se hizo un estudio de corte transversal con 48 niños sin enfermedad renal ni restricciones en la dieta, atendidos en consulta pediátrica entre enero y junio del 2011, el cual incluyó una encuesta sobre la dieta a los padres y la clasificación del estado nutricional por antropometría y medición de la presión arterial. Se analizaron el contenido de sodio y demás nutrientes de la dieta con el Programa Internacional de Consumo de Alimentos (CERES), las medidas antropométricas con el programa Anthro de la Organización Mundial de la Salud y las características sociodemográficas con el programa de Epi-info. Resultados. El 69 % de los niños tenía un consumo alto de sodio, el 6,2 % presentaba presión arterial elevada, y el 20,7 %, sobrepeso y obesidad. Conclusiones. La prevalencia de hipertensión arterial sistémica superó la informada para Colombia (1 a 3 %). Dos de los tres niños con presión arterial elevada tenían una dieta rica en sodio, así como sobrepeso y obesidad con valores superiores a lo informado para Colombia (16 %). Se sugiere medir la presión arterial tempranamente, recomendar la restricción de sal y azúcar en la alimentación de los menores de dos años, desarrollar estudios más grandes para obtener datos poblacionales sobre la ingestión de sodio, y diseñar estrategias de intervención, adecuadas y oportunas, para disminuir los riesgos en la edad adulta.

Abstract Introduction: The fatty streaks in an arterial wall can appear from the third year of age, and they show an association with atherogenic risk factors such as hypertension and sodium in the diet. Given the difficulty of data gathering, few studies report the intake of sodium in the diet. Objective: To determine average sodium intake in the diet of children between one and 18 months of age through a three-day dietary survey. Materials and methods: This was a cross-sectional study with 48 children without renal disease or diet restrictions seen in pediatric practice between January and June, 2011. It included a dietary survey for the parents, nutritional status classification by anthropometry, and blood pressure measurements. Sodium content and other nutrients in the diet program were analyzed with the International Food Consumption Program (CERES), anthropometry with the World Health Organization Anthro program, and Epi-info for socio-demographic characteristics. Results: In total, 69% of children had high sodium consumption, 6.2% had high blood pressure, and 20.7% were overweight and obese. Conclusions: The prevalence of hypertension exceeds that reported for Colombia (1-3%). Two of the three children with high blood pressure had high sodium intake and they were overweight and obese, with values above those reported for Colombian children (16%). We suggest to measure blood pressure early, and to restrict salt and sugar in food for infants and children under two years of age. Also, larger studies should be conducted to collect population data on sodium intake and develop appropriate and timely intervention strategies to reduce risks in adulthood.

Factores asociados con el éxito de la terapia antitabaco en pacientes tratados con vareniclina: 10 años de experiencia en un programa multidisciplinario / Factors associated with success of a smoking cessation program

Background: Smoking cessation therapies include counseling, psychological management and pharmacological therapy. Varenicline is the most effective and safe medication available. Aim: To study risk factors for the failure of pharmacological smoking cessation therapy with varenicline. Patients and Methods: Retrospective analysis of 281 patients aged 45 ± 11 years (65% males) with a mean consumption of 31 ± 22 packs/year. They completed a smoking cessation program comprising psychological support and use of varenicline in a private clinic. Patients were followed with telephonic interviews during one year. A complete abstinence during one year was considered as a success of the program. Results: The success rate of the program was 53.4%. The factors associated with failure were a high tobacco dependence rate determined with the Fageström test (Odds ratio (OR) 2.47, 95% confidence intervals (CI) 1.16-5.26, p = 0.02). An instruction level of more than 12 years was associated with a lower failure rate (OR 0.38 95% CI 0.18-0.82). Conclusions: A high tobacco dependence rate and a lower education were associated with a higher failure rate of this smoking cessation program.

Association between duration of untreated bipolar disorder and clinical outcome: data from a Brazilian sample

Objective: Bipolar disorder (BD) is often left untreated for long periods, and this delay in treatment correlates with unfavorable prognosis. The present study sought to assess the magnitude of duration of untreated bipolar disorder (DUB) in Brazil. We hypothesized that DUB would be longer in Brazil than in developed countries, and would be associated with poor clinical outcomes. Methods: One hundred and fifty-two psychiatric outpatients were evaluated for BD diagnosis, demographics, DUB, and clinical outcomes. Results: The mean age and mean DUB were, respectively, 38.9±10.8 and 10.4±9.8 years. An extended DUB was associated with early onset of BD (p < 0.001), depression as first mood episode (p = 0.04), and presence of BD in a first-degree relative (p = 0.012). Additionally, a longer DUB was associated with poorer clinical outcomes, such as elevated rates of rapid cycling (p = 0.004) and anxiety disorders (p = 0.016), as well as lower levels of current full remission (p = 0.021). Conclusion: As DUB may be a modifiable variable, better medical education regarding mental health, more structured medical services, and population-wide psychoeducation might reduce the time between onset and proper management of BD, thus improving outcome.

Diretrizes de conduta e tratamento de síndromes febris periódicas associadas à criopirina (criopirinopatias – CAPS) / Guidelines for the management and treatment of periodic fever syndromes

Resumo Objetivo: Estabelecer diretrizes baseadas em evidências científicas para manejo das síndromes periódicas associadas à criopirina (criopirinopatias – Caps). Descrição do método de coleta de evidência: A diretriz foi elaborada a partir de quatro questões clínicas que foram estruturadas por meio do PICO (Paciente, Intervenção ou Indicador, Comparação e Outcome), com busca nas principais bases primárias de informação científica. Após definir os estudos potenciais para sustento das recomendações, esses foram graduados pela força da evidência e pelo grau de recomendação. Resultado: Foram recuperados, e avaliados pelo título e resumo, 1.215 artigos e selecionados 42 trabalhos para sustentar as recomendações. Recomendações: 1. O diagnóstico de Caps é baseado na anamnese e nas manifestações clínicas e posteriormente confirmado por estudo genético. Pode se manifestar sob três fenótipos: FCAS (forma leve), MWS (forma intermediária) e Cinca (forma grave). Avaliações neurológica, oftalmológica, otorrinolaringológica e radiológica podem ser de grande valia na distinção entre as síndromes; 2. O diagnóstico genético com análise do gene NLRP3 deve ser conduzido nos casos suspeitos de Caps, isto é, indivíduos que apresentam, antes dos 20 anos, episódios recorrentes de inflamação expressa por urticária e febre moderada; 3. As alterações laboratoriais incluem leucocitose e elevação nos níveis séricos de proteínas inflamatórias; 4. Terapias alvo dirigidas contra a interleucina 1 levam a rápida remissão dos sintomas na maioria dos pacientes. Contudo, existem limitações importantes em relação à segurança em longo prazo. Nenhuma das três medicações anti-IL1β evita progressão das lesões ósseas.

Abstract Objective: To establish guidelines based on cientific evidences for the management of cryopyrin associated periodic syndromes. Description of the evidence collection method: The Guideline was prepared from 4 clinical questions that were structured through PICO (Patient, Intervention or indicator, Comparison and Outcome), to search in key primary scientific information databases. After defining the potential studies to support the recommendations, these were graduated considering their strength of evidence and grade of recommendation. Results: 1215 articles were retrieved and evaluated by title and abstract; from these, 42 articles were selected to support the recommendations. Recommendations: 1. The diagnosis of CAPS is based on clinical history and clinical manifestations, and later confirmed by genetic study. CAPS may manifest itself in three phenotypes: FCAS (mild form), MWS (intermediate form) and CINCA (severe form). Neurological, ophthalmic, otorhinolaryngological and radiological assessments may be highly valuable in distinguishing between syndromes; 2. The genetic diagnosis with NLRP3 gene analysis must be conducted in suspected cases of CAPS, i.e., individuals presenting before 20 years of age, recurrent episodes of inflammation expressed by a mild fever and urticaria; 3. Laboratory abnormalities include leukocytosis and elevated serum levels of inflammatory proteins; and 4. Targeted therapies directed against interleukin-1 lead to rapid remission of symptoms in most patients. However, there are important limitations on the long-term safety. None of the three anti-IL-1β inhibitors prevents progression of bone lesions.