Adherence to treatment of children and adolescents recently diagnosed with auto-immune Rheumatic Diseases during the COVID-19 pandemic

Abstract Objectives Adherence problems have a great impact on auto-immune Rheumatic Diseases (AIRD). The COVID-19 pandemic may have worsened treatment adherence. The aims of this study were to measure treatment adherence to identify an earlier risk of poor adherence and measure families' satisfaction with the health service during the pandemic. Methods Prospective observational study with 50 parents/children and adolescents with recent AIRD diagnosis. Initially, they answered questions (demographic data, disease) and completed the Pediatric Rheumatology Adherence Questionnaire (PRAQ), after 6 months they completed the Morisky-Green Test (MGT), Brief Medication Questionnaire (BMQ), Compliance Questionnaire for Rheumatology (CQR-19) and Pediatric Quality of Life Inventory Questionnaire 3.0 (PedsQlTM-SSS). The patient's medical records from the previous 12 weeks were reviewed for global and medication adherence data. Results The mean global adherence score was 94.3 ± 10.0, for medication adherence 97.3 ± 9.3, and for PRAQ questionnaire 5.2 ± 1.5. The authors observed agreement between MGT, BMQ, CQR-19, PedsQLTM-SSS scores and medication adherence rate, but not with global adherence rate. There were no associations between demographic characteristics, disease diagnosis, and adherence. No associations between PRAQ scores and values and global/medication adherence rates were observed. No variables were shown to be predictors of good adherence. The mean PedsQLTM-SSS rate was 92.1 ± 6.8. Conclusion The high values of MGT, BMQ, CQR-19 questionnaire scores were in agreement with the medication adherence rate. Despite the pandemic, the global and medication adherence rates were good. It was not possible to demonstrate the PRAQ's predictive power. The authors weren't able to establish an association between families' satisfaction and treatment adherence rates.

Adherence to treatment of children and adolescents recently diagnosed with auto-immune Rheumatic Diseases during the COVID-19 pandemic.

OBJECTIVES: Adherence problems have a great impact on auto-immune Rheumatic Diseases (AIRD). The COVID-19 pandemic may have worsened treatment adherence. The aims of this study were to measure treatment adherence to identify an earlier risk of poor adherence and measure families' satisfaction with the health service during the pandemic. METHODS: Prospective observational study with 50 parents/children and adolescents with recent AIRD diagnosis. Initially, they answered questions (demographic data, disease) and completed the Pediatric Rheumatology Adherence Questionnaire (PRAQ), after 6 months they completed the Morisky-Green Test (MGT), Brief Medication Questionnaire (BMQ), Compliance Questionnaire for Rheumatology (CQR-19) and Pediatric Quality of Life Inventory Questionnaire 3.0 (PedsQlTM-SSS). The patient's medical records from the previous 12 weeks were reviewed for global and medication adherence data. RESULTS: The mean global adherence score was 94.3 ± 10.0, for medication adherence 97.3 ± 9.3, and for PRAQ questionnaire 5.2 ± 1.5. The authors observed agreement between MGT, BMQ, CQR-19, PedsQLTM-SSS scores and medication adherence rate, but not with global adherence rate. There were no associations between demographic characteristics, disease diagnosis, and adherence. No associations between PRAQ scores and values and global/medication adherence rates were observed. No variables were shown to be predictors of good adherence. The mean PedsQLTM-SSS rate was 92.1 ± 6.8. CONCLUSION: The high values of MGT, BMQ, CQR-19 questionnaire scores were in agreement with the medication adherence rate. Despite the pandemic, the global and medication adherence rates were good. It was not possible to demonstrate the PRAQ's predictive power. The authors weren't able to establish an association between families' satisfaction and treatment adherence rates.

Sleep and restless legs syndrome in female adolescents with idiopathic musculoskeletal pain / Sono e síndrome das pernas inquietas em adolescentes do sexo feminino com dor musculoesquelética idiopática

Abstract Objectives: To assess the presence of restless legs syndrome, periodic leg movement, and sleep disorders in female adolescents with idiopathic musculoskeletal pain through a sleep scale and polysomnography, and to compare these data in adolescents without pain history. Method: Twenty-six adolescents diagnosed with idiopathic musculoskeletal pain followed in a pain outpatient clinic and 25 healthy controls matched by age and education were recruited. The restless legs syndrome criteria were evaluated according to the International Restless Legs Syndrome Study Group, the Sleep Disturbance Scale for Children was completed, nocturnal polysomnography was performed, and anxiety symptoms were recorded. Results: The mean age of idiopathic musculoskeletal pain adolescents was 13.9 ± 1.6 years; in controls, it was 14.4 ± 1.4 years. One adolescent in the control group (4 %) and nine patients with idiopathic musculoskeletal pain (34.6 %) fulfilled the restless legs syndrome criteria (p = 0.011). The authors did not observe significant differences in Sleep Disturbance Scale for Children scores between the groups in all components: disorders of initiating and maintaining sleep (p = 0.290), sleep breathing disorders (p = 0.576), disorders of arousal (p = 0.162), sleep-wake transition disorders (p = 0.258), disorder of excessive daytime somnolence (p = 0.594), and sleep hyperhidrosis (p = 0.797). The neurophysiological, respiratory, and periodic leg movement parameters were similar in both groups. Having anxiety was not associated with restless legs syndrome (p = 0.11). Three patients with idiopathic musculoskeletal pain (11.5 %) presented restless legs syndrome and periodic leg movement simultaneously, which was absent in the control group. Conclusion: Female adolescents with idiopathic musculoskeletal pain present criteria for RLS more frequently than healthy adolescents. However, this study did not observe relevant changes in objective and subject sleep variables.

Resumo Objetivos: Avaliar a presença de síndrome das pernas inquietas, movimento periódico das pernas e distúrbios do sono em adolescentes do sexo feminino com dor musculoesquelética idiopática por meio da escala do sono e da polissonografia e comparar esses dados em adolescentes sem histórico de dor. Método: Foram recrutados 26 adolescentes diagnosticados com dor musculoesquelética idiopática acompanhados em um ambulatório de dor e 25 controles saudáveis pareados por idade e escolaridade. Avaliamos os critérios da síndrome das pernas inquietas de acordo com o Grupo Internacional de Estudos de Síndrome das Pernas Inquietas, a Escala de Distúrbios do Sono em Crianças, a polissonografia noturna e os sintomas de ansiedade. Resultados: A idade média dos adolescentes com dor musculoesquelética idiopática foi 13,9 ± 1,6 anos e dos controles foi 14,4 ± 1,4 anos. Um adolescente no grupo de controle (4%) e nove pacientes com dor musculoesquelética idiopática (34,6%) atenderam aos critérios da síndrome das pernas inquietas (p = 0,011). Não observamos diferenças significativas nos escores da Escala de Distúrbios do Sono em Crianças entre os grupos em todos os componentes: distúrbios do início e da manutenção do sono (p = 0,290), distúrbios respiratórios do sono (p = 0,576), distúrbios do despertar (p = 0,162), distúrbios da transição sono-vigília (p = 0,258), sonolência diurna excessiva (p = 0,594) e hiperidrose do sono (p = 0,797). Os parâmetros neurofisiológicos, respiratórios e o movimento periódico das pernas foram semelhantes nos dois grupos. Ansiedade não foi associada à síndrome das pernas inquietas (p = 0,11). Três pacientes com dor musculoesquelética idiopática (11,5%) apresentaram síndrome das pernas inquietas e movimento periódico das pernas simultaneamente, situação ausente no grupo de controle. Conclusão: As adolescentes do sexo feminino com dor musculoesquelética idiopática apresentaram critérios para síndrome das pernas inquietas com mais frequência do que as adolescentes saudáveis. Contudo, não observamos mudanças relevantes nas variáveis do sono objetivas e subjetivas.

Sleep and restless legs syndrome in female adolescents with idiopathic musculoskeletal pain.

OBJECTIVES: To assess the presence of restless legs syndrome, periodic leg movement, and sleep disorders in female adolescents with idiopathic musculoskeletal pain through a sleep scale and polysomnography, and to compare these data in adolescents without pain history. METHOD: Twenty-six adolescents diagnosed with idiopathic musculoskeletal pain followed in a pain outpatient clinic and 25 healthy controls matched by age and education were recruited. The restless legs syndrome criteria were evaluated according to the International Restless Legs Syndrome Study Group, the Sleep Disturbance Scale for Children was completed, nocturnal polysomnography was performed, and anxiety symptoms were recorded. RESULTS: The mean age of idiopathic musculoskeletal pain adolescents was 13.9±1.6 years; in controls, it was 14.4±1.4 years. One adolescent in the control group (4 %) and nine patients with idiopathic musculoskeletal pain (34.6 %) fulfilled the restless legs syndrome criteria (p=0.011). The authors did not observe significant differences in Sleep Disturbance Scale for Children scores between the groups in all components: disorders of initiating and maintaining sleep (p=0.290), sleep breathing disorders (p=0.576), disorders of arousal (p=0.162), sleep-wake transition disorders (p=0.258), disorder of excessive daytime somnolence (p=0.594), and sleep hyperhidrosis (p=0.797). The neurophysiological, respiratory, and periodic leg movement parameters were similar in both groups. Having anxiety was not associated with restless legs syndrome (p=0.11). Three patients with idiopathic musculoskeletal pain (11.5 %) presented restless legs syndrome and periodic leg movement simultaneously, which was absent in the control group. CONCLUSION: Female adolescents with idiopathic musculoskeletal pain present criteria for RLS more frequently than healthy adolescents. However, this study did not observe relevant changes in objective and subject sleep variables.

Early detection of poor adherence to treatment of pediatric rheumatic diseases: pediatric rheumatology adherence questionnaire - a pilot study / Detecção precoce da má adesão ao tratamento em doenças reumáticas pediátricas: questionário de adesão em reumatologia pediátrica - estudo piloto

ABSTRACT Objective: To develop a questionnaire that allows the early detection of patients at risk for poor adherence to medical and non-medical treatment in children and adolescents with chronic rheumatic diseases. Methods: The Pediatric Rheumatology Adherence Questionnaire (PRAQ) was applied in recently diagnosed patients within a period of one to four months after confirmation of the rheumatic disease. After six months, the patients' adherence to the medical and non-medical treatment was assessed. An internal consistency analysis was conducted to eliminate redundant questions in the PRAQ. Results: A total of 33 patients were included in the pilot study. Six months after the PRAQ had been applied, poor global adherence was observed in seven (21.2%) patients and poor adherence to medical treatment in eight (24.2%) patients. No correlation was observed between the PRAQ scores and the percentages of adherence, as well as the stratification for each index, except for a tendency to a correlation between socioeconomic index and poor adherence to medical treatment (p=0.08). A new PRAQ questionnaire with 25 of the 46 original questions was generated as a result of the reliability analysis. Conclusions: The usefulness of this questionnaire in clinical practice should be still evaluated. Due to the importance of a tool for the early detection of rheumatic patients at risk of poor adherence to treatment, the new PRAQ questionnaire should be reviewed and applied in a larger study to better define its validity and reliability.

RESUMO Objetivo: Desenvolver um questionário que permitisse a detecção precoce de pacientes em risco de má adesão ao tratamento medicamentoso e não medicamentoso para crianças e adolescentes com doenças reumáticas crônicas. Métodos: O Questionário de Adesão em Reumatologia Pediátrica (QARP) foi aplicado em pacientes recentemente diagnosticados, de um a quatro meses após a confirmação da doença reumática. Seis meses depois, foi avaliada a adesão do paciente ao tratamento medicamentoso e não medicamentoso. Foi realizada uma análise de consistência interna para eliminar questões redundantes no QARP. Resultados: Ao todo, 33 pacientes foram incluídos no estudo-piloto. Seis meses após a aplicação do QARP, observou-se baixa adesão global em sete pacientes (21,2%) e baixa adesão ao tratamento medicamentoso em oito (24,2%) pacientes. Não foi encontrada correlação entre os escores QARP e as porcentagens de adesão, bem como a estratificação para cada indicador, com exceção de uma tendência a uma correlação entre o indicador socioeconômico e a baixa adesão ao tratamento medicamentoso (p=0,08). Um novo questionário QARP com 25 das 46 perguntas originais foi gerado como resultado da análise de confiabilidade. Conclusões: A utilidade deste questionário na prática clínica ainda deve ser avaliada. Devido à importância de uma ferramenta para a detecção precoce de pacientes reumáticos em risco de má adesão ao tratamento, o novo questionário QARP deve ser revisado e aplicado em um estudo maior para que sua validade e confiabilidade sejam mais bem definidas.

EARLY DETECTION OF POOR ADHERENCE TO TREATMENT OF PEDIATRIC RHEUMATIC DISEASES: PEDIATRIC RHEUMATOLOGY ADHERENCE QUESTIONNAIRE - A PILOT STUDY.

OBJECTIVE: To develop a questionnaire that allows the early detection of patients at risk for poor adherence to medical and non-medical treatment in children and adolescents with chronic rheumatic diseases. METHODS: The Pediatric Rheumatology Adherence Questionnaire (PRAQ) was applied in recently diagnosed patients within a period of one to four months after confirmation of the rheumatic disease. After six months, the patients' adherence to the medical and non-medical treatment was assessed. An internal consistency analysis was conducted to eliminate redundant questions in the PRAQ. RESULTS: A total of 33 patients were included in the pilot study. Six months after the PRAQ had been applied, poor global adherence was observed in seven (21.2%) patients and poor adherence to medical treatment in eight (24.2%) patients. No correlation was observed between the PRAQ scores and the percentages of adherence, as well as the stratification for each index, except for a tendency to a correlation between socioeconomic index and poor adherence to medical treatment (p=0.08). A new PRAQ questionnaire with 25 of the 46 original questions was generated as a result of the reliability analysis. CONCLUSIONS: The usefulness of this questionnaire in clinical practice should be still evaluated. Due to the importance of a tool for the early detection of rheumatic patients at risk of poor adherence to treatment, the new PRAQ questionnaire should be reviewed and applied in a larger study to better define its validity and reliability.

Psychological characteristics of caregivers of pediatric patients with chronic rheumatic disease in relation to treatment adherence.

BACKGROUND: Adherence to treatment for chronic diseases is lower in children than in adults, less extensively studied in children and is associated with multiple related factors. The aim of this study is to perform a descriptive analysis of psycho-cognitive aspects of primary caregivers of pediatric patients with chronic rheumatic diseases, as well as socioeconomic and clinical factors, family functioning and treatment satisfaction. METHODS: Primary caregivers of 90 patients were included. Pairs (caregiver plus patient) were grouped as presenting good adherence (n = 50) or poor adherence (n = 40) according to the Morisky Adherence Test. Psycho-cognitive aspects were evaluated by Adult Self-Report and Wechsler Adult Intelligence Scale tests. For statistical comparisons, quantitative variables with normal distribution were analyzed by Student's t test, and those with non-Gaussian distribution with the Mann Whitney test. Categorical variables were analyzed by Chi square test. A multivariate logistic regression analysis was performed to estimate the contribution of the independent variables to adherence. RESULTS: Compared to caregivers in the good adherence group, caregivers in the poor adherence group were more likely to be classified as clinical on the scales for attention problems and externalizing problems, which include impulsiveness and aggressiveness. They also scored higher on the depressive problem scale. In addition, the average number of children per caregiver and the mean age of caregivers and patients were significantly higher in the poor adherence group, while the proportion of caregivers with higher education was lower. The poor adherence group also included a higher incidence of pediatric patients assuming sole responsibility for managing medications. Economic status, clinical factors, treatment satisfaction, family functioning and caregiver cognitive profile were not related to adherence, except for working memory index. CONCLUSION: Older patients, patients as the one solely responsible for medication management, and caregivers with externalizing problems, were observed to be the most strongly associated to poor adherence. Interventions aimed at adolescent patients are needed. Also, psychological programs and interventional studies to better determine caregivers' behavioral/emotional status, and parent-child relationships are recommended.

Patients with juvenile idiopathic arthritis in clinical remission with positive power Doppler signal in joint ultrasonography have an increased rate of clinical flare: a prospective study.

BACKGROUND: Ultrasonography (US) studies carried out on joints of juvenile idiopathic arthritis (JIA) patients in clinical remission demonstrate the presence of subclinical synovitis. The significance of subclinical synovitis and the positive power Doppler (PD) signal on US in JIA in clinical remission is not well understood. The objectives of this study were to assess whether the changes detected by US in patients with JIA in clinical remission can predict disease flare and to evaluate factors associated with flare and joint damage over 30 months of follow-up. METHODS: A prospective study was performed with clinical and ultrasound evaluation in 34 joints of JIA patients in clinical remission. Clinical evaluation including physical exam, functional capacity and inflammatory markers was performed at baseline and every six months thereafter, for a total period of 30 months. US evaluation included presence of synovitis, PD signal and erosion at baseline and every 12 months thereafter. Subclinical synovitis was defined when there was synovitis with or without positive PD signal in US joints of patients in clinical remission. Flare was defined as any joint presenting clinical arthritis requiring therapy modification. RESULTS: We evaluated a total of 35 patients, 28 (80%) girls, 14 (40%) persistent oligoarticular subtype, 12 (34.3%) oligoarticular extended and 9 (25.7%) polyarticular and 26 (74.3%) in remission on medication. Twenty (57.1%) patients flared. The risk of flare was five times higher in patients with positive PD signal and 14 times higher in patients in remission on medication. Regarding the assessment of joints after 6 months and 12 months of US evaluation, 70/3162 (2.2%) joints and 80/2108 (3.8%) joints flared, respectively. Joints with subclinical synovitis with positive PD signal flared more after 6 and 12 months. Twenty five of 2108 (1.2%) joints showed erosion over time. Joints with subclinical synovitis with or without positive PD signal showed more erosion. CONCLUSIONS: Patients in remission on medication with subclinical synovitis with positive PD signal on US have a higher risk of flare, therefore they should be monitored closely during treatment. In the same way, joints with subclinical synovitis with or without positive PD signal should be monitored due to the risk of flare and joint damage.

Intra-articular injection in patients with juvenile idiopathic arthritis: factors associated with a good response.

INTRODUCTION: Intra-articular injection of corticosteroids (IIC) for treatment of patients with juvenile idiopathic arthritis (JIA) is increasingly used in Pediatric Rheumatology. OBJECTIVES: To describe the clinical course of patients undergoing IIC in our Pediatric Rheumatology Unit. METHODS: Retrospective study of patients with JIA undergoing IIC from January 2008 to December 2012, with a minimum follow-up of six months after the injection. Good response to IIC was set as the presence of inactivity on the infiltrated joint by at least six months. RESULTS: Eighty-eight patients underwent a total of 165 IICs. Of these, 75% were girls and 35.2% had persistent oligoarticular JIA. The mean age at diagnosis was 6.8 years, and when IIC was carried out, 12.2 years. Regarding patients, younger age at diagnosis (p=0.037) and the occurrence of uveitis in the course of the disease (p=0.015) were associated with good response to IIC. From 165 IICs, 63% had a good response and joints remained inactive for a median of 18.1 months. The type of joint injection (p=0.001), lesser values stated in the overall visual analog scale by the physician (p=0.015) and by parents/patient (p=0.01) have been associated with a good response to IIC. Nine adverse events (5.4%) were observed. CONCLUSION: In our study, more than half of the joints showed a good response to IIC. Younger patients at diagnosis and uveitis during the course of the disease had good response to IIC. Knees, wrists and elbows were the joints that best responded to IIC. IIC proved to be a safe procedure.

Intra-articular injection in patients with juvenile idiopathic arthritis: factors associated with a good response / Infiltração intra-articular em pacientes com artrite idiopática juvenil: fatores associados à boa resposta

ABSTRACT Introduction: Intra-articular injection of corticosteroids (IIC) for treatment of patients with juvenile idiopathic arthritis (JIA) is increasingly used in Pediatric Rheumatology. Objectives: To describe the clinical course of patients undergoing IIC in our Pediatric Rheumatology Unit. Methods: Retrospective study of patients with JIA undergoing IIC from January 2008 to December 2012, with a minimum follow-up of six months after the injection. Good response to IIC was set as the presence of inactivity on the infiltrated joint by at least six months. Results: Eighty-eight patients underwent a total of 165 IICs. Of these, 75% were girls and 35.2% had persistent oligoarticular JIA. The mean age at diagnosis was 6.8 years, and when IIC was carried out, 12.2 years. Regarding patients, younger age at diagnosis (p = 0.037) and the occurrence of uveitis in the course of the disease (p = 0.015) were associated with good response to IIC. From 165 IICs, 63% had a good response and joints remained inactive for a median of 18.1 months. The type of joint injection (p = 0.001), lesser values stated in the overall visual analog scale by the physician (p = 0.015) and by parents/patient (p = 0.01) have been associated with a good response to IIC. Nine adverse events (5.4%) were observed. Conclusion: In our study, more than half of the joints showed a good response to IIC. Younger patients at diagnosis and uveitis during the course of the disease had good response to IIC. Knees, wrists and elbows were the joints that best responded to IIC. IIC proved to be a safe procedure.

RESUMO Introdução: A infiltração intra-articular de corticosteroides (IIC) para tratamento de pacientes com artrite idiopática juvenil (AIJ) é cada vez mais usada em reumatologia pediátrica. Objetivos: Descrever a evolução clínica dos pacientes submetidos à IIC em nosso setor de reumatologia pediátrica. Métodos: Estudo retrospectivo de pacientes com AIJ submetidos à IIC de janeiro/2008 a dezembro/2012, com seguimento mínimo de seis meses após a infiltração. Boa resposta à IIC foi definida como inatividade na articulação infiltrada por, no mínimo, seis meses. Resultados: Foram submetidos a 88 pacientes a 165 IICs. Desses, 75% eram meninas e 35,2% apresentavam AIJ oligoarticular persistente. A média de idade ao diagnóstico foi de 6,8 anos e à IIC de 12,2 anos. Em relação aos pacientes, a menor idade ao diagnóstico (p = 0,037) e a ocorrência de uveíte no curso da doença (p = 0,015) foram associados à boa resposta à IIC. Das 165 IICs, 63% apresentaram boa resposta e as articulações permaneceram inativas por um tempo médio de 18,1 meses. O tipo de articulação infiltrada (p = 0,001), menores valores na escala visual analógica global do médico (p = 0,015) e dos pais/paciente (p = 0,01) foram associados a uma boa resposta à IIC. Nove efeitos adversos (5,4%) foram observados. Conclusão: Em nosso estudo, mais da metade das articulações mostrou boa resposta à IIC. Os pacientes com menor idade ao diagnóstico e uveíte durante o curso da doença tiveram boa resposta à IIC. Os joelhos, punhos e cotovelos foram as articulações que mais bem responderam à IIC. A IIC mostrou ser um procedimento seguro.

Intra-articular injection in patients with juvenile idiopathic arthritis: factors associated with a good response. / Infiltração intra-articular em pacientes com artrite idiopática juvenil: fatores associados à boa resposta.

INTRODUCTION: Intra-articular injection of corticosteroids (IIC) for treatment of patients with juvenile idiopathic arthritis (JIA) is increasingly used in Pediatric Rheumatology. OBJECTIVES: To describe the clinical course of patients undergoing IIC in our Pediatric Rheumatology Unit. METHODS: Retrospective study of patients with JIA undergoing IIC from January 2008 to December 2012, with a minimum follow-up of six months after the injection. Good response to IIC was set as the presence of inactivity on the infiltrated joint by at least six months. RESULTS: Eighty-eight patients underwent a total of 165 IICs. Of these, 75% were girls and 35.2% had persistent oligoarticular JIA. The mean age at diagnosis was 6.8 years, and when IIC was carried out, 12.2 years. Regarding patients, younger age at diagnosis (p=0.037) and the occurrence of uveitis in the course of the disease (p=0.015) were associated with good response to IIC. From 165 IICs, 63% had a good response and joints remained inactive for a median of 18.1 months. The type of joint injection (p=0.001), lesser values stated in the overall visual analogue scale by the physician (p=0.015) and by parents/patient (p=0.01) have been associated with a good response to IIC. Nine adverse events (5.4%) were observed. CONCLUSION: In our study, more than half of the joints showed a good response to IIC. Younger patients at diagnosis and uveitis during the course of the disease had good response to IIC. Knees, wrists and elbows were the joints that best responded to IIC. IIC proved to be a safe procedure.

Importance of adherence in the outcome of juvenile idiopathic arthritis.

Medical treatment of juvenile idiopathic arthritis (JIA) has advanced in the last decade, and improved prognosis is a reality in daily clinical practice. Despite this improvement in the quality of treatment, the outcome can still be compromised by modifiable factors, including delayed referral to a specialist, delayed drug treatment, poor adherence to treatment, and early interruption of drug treatment. In this review we discuss the most relevant aspects related to adherence to treatment in JIA, with emphasis on: factors that affect adherence to treatment; effect of poor adherence to treatment on JIA prognosis; when to suspect and how to assess poor adherence to treatment; and strategies to promote adherence to treatment, with an emphasis on information-reinforcement education. Besides presenting the findings of other authors, we also try to report our experience of this subject, which is still a challenge for health professionals.

Laser Doppler imaging for assessment of microcirculation in juvenile systemic sclerosis.

OBJECTIVES: The objectives of this study were to evaluate the dynamic behaviour of digital skin microvascular blood flow before and after cold stimulation using laser Doppler imaging (LDI) in children and adolescents with RP secondary to juvenile systemic sclerosis (JSS), primary RP (PRP) and healthy controls and to compare functional abnormalities measured by LDI with structural microvascular abnormalities evaluated by nailfold capillaroscopy (NFC). METHODS: Five JSS patients, five children and adolescents with PRP and five healthy controls matched for gender and age were included. All subjects had NFC performed. Finger blood flow (FBF) was measured using the LDI system (Moor Instruments) at baseline and after cold stimulus (CS). RESULTS: There were a decreased number of capillaries, a greater number of enlarged capillaries and a higher deletion score in JSS patients compared with controls and patients with PRP. The mean baseline FBF was significantly lower in JSS patients compared with controls. There was no difference between the mean baseline FBF in JSS patients compared with patients with PRP. There was a significant decrease in FBF 1 min after CS in all groups followed by blood flow recovery at 20 min after CS in comparison with basal FBF values in controls, but not in JSS and PRP patients. CONCLUSION: In JSS patients, LDI showed a lower FBF before and after CS compared with healthy controls and may be an objective and sensitive method for the measurement of digital skin blood flow in RP children.

Do patients with juvenile idiopathic arthritis in remission exhibit active synovitis on joint ultrasound?

The aim of the study was to assess the presence and characteristics of subclinical synovitis using power Doppler (PD) ultrasonography on patients with juvenile idiopathic arthritis (JIA) in clinical remission and compare the findings with those of healthy children. A cross-sectional study was carried out involving the clinical (physical exam, functional capacity and laboratory tests) and ultrasonography evaluation of 34 joints (synovial fluid/hypertrophy, PD signal and bone erosion). Subclinical synovitis was defined as the presence of synovial hypertrophy/joint effusion with or without any PD signal. Thirty-six patients (11.5 ± 3.74 years) and 36 controls (sex and age matched) were evaluated (2,448 joints). Twenty-seven patients were in remission on medication (mean duration: 1.8 ± 2.2 years). Subclinical synovitis was detected in 41.7% patients and 11.1% controls (p = 0.003). Erosion was detected in three patients (8.3%). Subclinical synovitis was found in 38/1,224 (3.1%) joints in the patients (most affected: radiocarpal wrist, anterior elbow and tibiotalar ankle) and 8/1,224 (0.6%) joints in the controls (most affected: radiocarpal wrist). Differences in subclinical synovitis between patients and controls were found in the elbows (p = 0.033) and ankles (p = 0.006). A greater frequency of subclinical synovitis was found in patients with the extended oligoarticular or polyarticular subtypes (p = 0.013), those at an older age at disease onset (p = 0.007) and using methotrexate (p = 0.049). Patients with JIA in remission exhibit subclinical synovitis more frequently than controls. Subclinical synovitis was more frequent in patients with the polyarticular involvement and those at an older age at disease onset.

Association between the ultrasonographic and clinical findings in the hips of patients with juvenile idiopathic arthritis.

OBJECTIVE: To describe the ultrasonographic (US) findings in the hips of patients with juvenile idiopathic arthritis (JIA) and the association between these findings and the signs, symptoms, and activity of the disease. MATERIALS AND METHODS: The present retrospective study included 92 patients with JIA. The disease subtypes, age at disease onset, length of disease progression, disease activity, and clinical manifestations of the hip pathology were assessed. US examinations were routinely performed, and the images were analysed by two ultrasonographers who were blinded to the patients' clinical conditions. RESULTS: Of the 92 patients included in the study, 69.6% were girls, and the average age was 12.4 ± 5.1 years. Thirty-three (35.9%) participants exhibited the persistent oligoarticular subtype, and 30 (32.6%) exhibited the rheumatoid factor (RF)-negative polyarticular subtype. Forty-four participants exhibited signs and/or symptoms of hip pathology. Twenty-nine (31.5%) participants exhibited abnormal US findings, and 34.4% exhibited subclinical synovitis. The US alterations exhibited an association with subclinical synovitis in 34.4% of the cases. The US alterations bore a correlation with the presence of hip-related signs and/ or symptoms (P = 0.021), particularly joint limitations (P = 0.006), but were not correlated with the disease activity (P = 0.948) or subtype (P = 0.108). Clinical synovitis was associated with polyarticular involvement (P = 0.002) and disease activity (P = 0.017). Subclinical synovitis was not correlated with the investigated variables. CONCLUSION: Clinical affection of the hip in JIA, particularly joint limitation, is associated with synovitis (revealed by US assessment) independently of the activity and subtype of the disease. Therefore, healthcare professionals should consider the possible occurrence of silent disease and subclinical synovitis, which might contribute to hip deterioration.

Associação entre achados ultrassonográficos e clínicos do quadril de pacientes com artrite idiopática juvenil / Association between the ultrasonographic and clinical findings in the hips of patients with juvenile idiopathic arthritis

OBJETIVO: Descrever os achados ultrassonográficos do quadril em pacientes com artrite idiopática juvenil (AIJ) e sua associação com sinais, sintomas e atividade da doença. MATERIAIS E MÉTODOS: Estudo retrospectivo com 92 pacientes com AIJ. Foram avaliados os subtipos da doença, a idade de início, o tempo de evolução, a atividade da doença e as manifestações clínicas do envolvimento do quadril. A avaliação ultrassonográfica foi realizada na rotina dos pacientes, e as imagens foram analisadas por dois ultrassonografistas cegos em relação às condições clínicas dos pacientes. RESULTADOS: Do total de 92 pacientes, 69,6% eram meninas, com média de idade de 12,4 ± 5,1 anos. Trinta e três (35,9%) apresentaram subtipo oligoarticular persistente e trinta (32,6%) poliarticular com fator reumatoide negativo. Quarenta e quatro (47,8%) apresentaram sinal e/ou sintoma relacionado ao quadril. Vinte e nove (31,5%) apresentaram alterações ultrassonográficas, com sinovite subclínica em 34,4%. As alterações ultrassonográficas se associaram com presença de sinais e/ou sintomas do quadril (P = 0,021), especialmente limitação articular (P = 0,006), mas não com atividade (P = 0,948) ou subtipo de doença (P = 0,108). Sinovite clínica se associou com comprometimento poliarticular (P = 0,002) e atividade de doença (P = 0,017). Não houve associação entre sinovite subclínica e as variáveis estudadas. CONCLUSÃO: O acometimento clínico do quadril na AIJ, especialmente a limitação articular, está associado à sinovite na avaliação por US, independente do subtipo e da atividade da doença. Os profissionais de saúde devem estar atentos à possibilidade de doença silenciosa com sinovite subclínica, que pode contribuir para a deterioração da articulação do quadril.

OBJECTIVE: To describe the ultrasonographic (US) findings in the hips of patients with juvenile idiopathic arthritis (JIA) and the association between these findings and the signs, symptoms, and activity of the disease. MATERIALS AND METHODS: The present retrospective study included 92 patients with JIA. The disease subtypes, age at disease onset, length of disease progression, disease activity, and clinical manifestations of the hip pathology were assessed. US examinations were routinely performed, and the images were analysed by two ultrasonographers who were blinded to the patients' clinical conditions. RESULTS: Of the 92 patients included in the study, 69.6% were girls, and the average age was 12.4 ± 5.1 years. Thirty-three (35.9%) participants exhibited the persistent oligoarticular subtype, and 30 (32.6%) exhibited the rheumatoid factor (RF)-negative polyarticular subtype. Forty-four participants exhibited signs and/or symptoms of hip pathology. Twentynine (31.5%) participants exhibited abnormal US findings, and 34.4% exhibited subclinical synovitis. The US alterations exhibited an association with subclinical synovitis in 34.4% of the cases. The US alterations bore a correlation with the presence of hip-related signs and/ or symptoms (P = 0.021), particularly joint limitations (P = 0.006), but were not correlated with the disease activity (P = 0.948) or subtype (P = 0.108). Clinical synovitis was associated with polyarticular involvement (P = 0.002) and disease activity (P = 0.017). Subclinical synovitis was not correlated with the investigated variables. CONCLUSION: Clinical affection of the hip in JIA, particularly joint limitation, is associated with synovitis (revealed by US assessment) independently of the activity and subtype of the disease. Therefore, healthcare professionals should consider the possible occurrence of silent disease and subclinical synovitis, which might contribute to hip deterioration.

microRNA-29 can regulate expression of the long non-coding RNA gene MEG3 in hepatocellular cancer.

The human genome is replete with long non-coding RNAs (lncRNA), many of which are transcribed and likely to have a functional role. Microarray analysis of >23,000 lncRNAs revealed downregulation of 712 (~3%) lncRNA in malignant hepatocytes, among which maternally expressed gene 3 (MEG3) was downregulated by 210-fold relative to expression in non-malignant hepatocytes. MEG3 expression was markedly reduced in four human hepatocellular cancer (HCC) cell lines compared with normal hepatocytes by real-time PCR. RNA in situ hybridization showed intense cytoplasmic expression of MEG3 in non-neoplastic liver with absent or very weak expression in HCC tissues. Enforced expression of MEG3 in HCC cells significantly decreased both anchorage-dependent and -independent cell growth, and induced apoptosis. MEG3 promoter hypermethylation was identified by methylation-specific PCR and MEG3 expression was increased with inhibition of methylation with either 5-Aza-2-Deoxycytidine, or siRNA to DNA Methyltransferase (DNMT) 1 and 3b in HCC cells. MiRNA-dependent regulation of MEG3 expression was studied by evaluating the involvement of miR-29, which can modulate DNMT 1 and 3. Overexpression of mir-29a increased expression of MEG3. GTL2, the murine homolog of MEG3, was reduced in liver tissues from hepatocyte-specific miR-29a/b1 knock-out mice compared with wild-type controls. These data show that methylation-dependent tissue-specific regulation of the lncRNA MEG3 by miR-29a may contribute to HCC growth and highlight the inter-relationship between two classes of non-coding RNA, miRNAs and lncRNAs, and epigenetic regulation of gene expression.

Associations of risk factors obesity and occupational airborne exposures with CDKN2A/p16 aberrant DNA methylation in esophageal cancer patients.

It is known that obesity and occupational airborne exposure such as dust are among risk factors of esophageal cancer development, in particular squamous cell carcinoma (SCC) of esophagus. Here, we tested whether these factors could also affect aberrant DNA methylation. DNAs from 44 fresh tumor tissues and 19 non-tumor adjacent normal tissues, obtained from 44 patients affected by SCC of esophagus (SCCE), were studied for methylation at the CDKN2A/p16 gene promoter by methylation-specific polymerase chain reaction assay. Statistical methods were used to assess association of promoter methylation with biopathological, clinical, and personal information data, including obesity and airborne exposures. Methylation at the CDKN2A/p16 gene promoter was detected in 12 out of 44 tumor samples. None of the non-tumor tissues exhibited the aberrant methylation. Our results confirmed previously described significant association with low tumor stage (P= 0.002); in addition, we found that obesity (P= 0.001) and occupational exposure (P= 0.008) were both significantly associated with CDKN2A/p16 promoter methylation. This study provides evidence that obesity and occupational exposure increase the risk of developing esophageal cancer through an enhancement of CDKN2A/p16 promoter methylation.

The methylator phenotype in microsatellite stable colorectal cancers is characterized by a distinct gene expression profile.

The CpG island methylator phenotype (CIMP) in colorectal tumours can be recognized by an increased frequency of aberrant methylation in a specific set of genomic loci. Because of the strong association of CIMP with high microsatellite instability (MSI-H), the identification of CIMP+ tumours within microsatellite stable (MSS) colorectal cancers may not be straightforward. To overcome this potential limitation, we have built an improved seven-locus set of methylation markers that includes CACNA1G, IGF2, RUNX3, HTR6, RIZ1, MINT31, and MAP1B. This new set of CIMP markers revealed a bimodal distribution of methylation frequencies in a group of 95 MSS colorectal cancers, which allowed a clearer separation between CIMP classes. Correlation of MSS CIMP+ tumours with bio-pathological traits revealed significant associations with location to the proximal colon, mucinous histology, BRAF mutation, and chromosomal stability. A potential trend towards an adverse prognosis of CIMP+ cases was associated with the high frequency of BRAF mutations present within this cohort of tumours. Microarray analysis revealed that CIMP+ tumours are characterized by a unique expression profile, a result that confirms that CIMP+ tumours represent a truly distinct molecular class within MSS colorectal cancers.