Evaluation of peripheral neuropathy in lower limbs of patients with rheumatoid arthritis and its relation to fall risk.

BACKGROUND: Rheumatoid Arthritis (RA) is a chronic disabling systemic disease characterized by joint inflammation, and extra-articular manifestations, including peripheral neuropathy, a condition that can be associated with changes in muscle strength, proprioception and postural balance contributing for the risk of falls. The objective of this study is to analyze the incidence of peripheral neuropathy in patients with RA and its association with the occurrence of falls. METHODS: Patients were assessed by an electroneuromyography (ENMG) exam and by a questionnaire on accidental falls occurrence in the previous 12 months. They were also assessed on balance by the Short Physical Performance Battery (SPPB), functionality by the Health Assessment Questionnaire (HAQ), disease activity by the Disease Activity Score (DAS-28), neuropathic pain by the Questionnaire for the Diagnosis of Neuropathic Pain (DN4), and cutaneous sensitivity of the feet by the monofilament testing of Semmes-Weinstein. Monthly calls on falls were made in the subsequent six months. Data analysis was performed using the Shapiro-Wilk test for normality and Spearman, Chi-square, and T-student correlation tests, with a significant P level ≤ 0.05. RESULTS: A sample of 33 patients were evaluated. The incidence of peripheral neuropathy was 48.5%, of which 68.7% were axonal and 31.3% myelinic. The sensorimotor type was present in 64.7%, motor in 17.6%, and sensorial in 11.7% of the cases. Neuropathy was associated to balance (P = 0.026), neuropathic pain (P = 0.016), deep tendon reflexes absence (P = 0,049), altered skin sensitivity of the feet (P = 0.029) and fear of falling (P = 0.001). No association was found between peripheral neuropathy and age, gender, disease activity, or functionality. No significant association was found between peripheral neuropathy and occurrence of falls, in a 12-month retrospective and 6-month prospective evaluation. CONCLUSION: Peripheral neuropathy has a high incidence in patients with RA, and is related to neuropathic pain, altered postural balance, but not to the occurrence of falls.

Treatment data from the Brazilian fibromyalgia registry (EpiFibro).

BACKGROUND: EpiFibro (Brazilian Epidemiological Study of Fibromyalgia) was created to study patients with fibromyalgia (FM). Patients were included since 2011 according to the classification criteria for FM of the American College of Rheumatology of 1990 (ACR1990). OBJECTIVE: To analyze the therapeutic measures prescribed by Brazilian physicians. MATERIALS AND METHODS: Cross-sectional study of a multicenter cohort. The therapeutic measures were described using descriptive statistics. RESULTS: We analyzed 456 patients who had complete data in the registry. The mean age was 54.0 ± 11.9 years; 448 were women (98.2%). Almost all patients (98.4%) used medications, 62.7% received health education, and less than half reported practicing physical exercise; these modalities were often used in combination. Most patients who practiced exercises practiced aerobic exercise only, and a significant portion of patients combined it with flexibility exercises. The most commonly used medication was amitriptyline, followed by cyclobenzaprine, and a minority used medication specifically approved for FM, such as duloxetine and pregabalin, either alone or in combination. Combinations of two or three medications were observed, with the combination of fluoxetine and amitriptyline being the most frequent (18.8%). CONCLUSION: In this evaluation of the care of patients with FM in Brazil, it was found that the majority of patients are treated with a combination of pharmacological measures. Non-pharmacological methods are underused, with aerobic exercise being the most commonly practiced exercise type. The most commonly prescribed single drug was amitriptyline, and the most commonly prescribed combination was fluoxetine and amitriptyline. Drugs specifically approved for FM are seldom prescribed.

Brazilian recommendations on the safety and effectiveness of the yellow fever vaccination in patients with chronic immune-mediated inflammatory diseases.

BACKGROUND: In Brazil, we are facing an alarming epidemic scenario of Yellow fever (YF), which is reaching the most populous areas of the country in unvaccinated people. Vaccination is the only effective tool to prevent YF. In special situations, such as patients with chronic immune-mediated inflammatory diseases (CIMID), undergoing immunosuppressive therapy, as a higher risk of severe adverse events may occur, assessment of the risk-benefit ratio of the yellow fever vaccine (YFV) should be performed on an individual level. Faced with the scarcity of specific orientation on YFV for this special group of patients, the Brazilian Rheumatology Society (BRS) endorsed a project aiming the development of individualized YFV recommendations for patients with CIMID, guided by questions addressed by both medical professionals and patients, followed an internationally validated methodology (GIN-McMaster Guideline Development). Firstly, a systematic review was carried out and an expert panel formed to take part of the decision process, comprising BRS clinical practitioners, as well as individuals from the Brazilian Dermatology Society (BDS), Brazilian Inflammatory Bowel Diseases Study Group (GEDIIB), and specialists on infectious diseases and vaccination (from Tropical Medicine, Infectious Diseases and Immunizations National Societies); in addition, two representatives of patient groups were included as members of the panel. When the quality of the evidence was low or there was a lack of evidence to determine the recommendations, the decisions were based on the expert opinion panel and a Delphi approach was performed. A recommendation was accepted upon achieving ≥80% agreement among the panel, including the patient representatives. As a result, eight recommendations were developed regarding the safety of YFV in patients with CIMID, considering the immunosuppression degree conferred by the treatment used. It was not possible to establish recommendations on the effectiveness of YFV in these patients as there is no consistent evidence to support these recommendations. CONCLUSION: This paper approaches a real need, assessed by clinicians and patient care groups, to address specific questions on the management of YFV in patients with CIMID living or traveling to YF endemic areas, involving specialists from many areas together with patients, and might have global applicability, contributing to and supporting vaccination practices. We recommended a shared decision-making approach on taking or not the YFV.

Strengths and weaknesses of the Brazilian regulation on biosimilars: A critical view of the regulatory requirements for biosimilars in Brazil.

Biological products or biopharmaceuticals are medicinal products derived from living systems and manufactured by modern biotechnological methods that differ widely from the traditional synthetic drugs. Monoclonal antibodies are the most rapidly growing type of biologic. They are much larger and more complex molecules with inherent diversity; therefore, different manufacturers cannot produce identical biological products, even with the same type of host expression system and equivalent technologies. Thus, legal follow-on biologics manufactured and marketed after patent expiration are usually referred to as biosimilars. Biosimilarity is based on a comparability exercise whereby unavoidable clinical differences are evaluated and must meet equivalence or non-inferiority criteria. Biosimilars need to comply with different regulatory requirements for market authorization in different sites. There are several other related issues that need to be defined by the national authorities, such as interchangeability, labeling and prescribing information. The Brazilian health surveillance agency follows the key principles established by the World Health Organization for the assessment of biosimilarity, although does not adopt the name 'biosimilar'. However, the agency also made a compromise on a standalone application pathway that does not require the usual comparability exercise with the reference product, originating nonbiosimilar copies. Interchangeability and the use of nonproprietary names are not regulated, giving rise to pressures on physicians and conflicts of interest in the decision making on biosimilar use. The scope of this article is to present the Brazilian regulation on biosimilars, its strengths and weaknesses, and to discuss it in the face of regulations in the USA and Europe.

Hand strength in patients with RA correlates strongly with function but not with activity of disease.

BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation of the joints, especially of the hands. The evaluation of handgrip strength (HS) and pinch strength can be useful to detect reduction in hand function in RA patients. The aim of the study was to compare HS and pinch strength between RA patients (RA Group - RAG) and a non-RA control group (CG) and to relate HS and pinch strength to functional capacity, duration and disease activity in the RAG. METHODS: A cross-sectional case control study. The RAG was assessed for disease activity by the Disease Activity Score (DAS-28); for functional capacity by the Health Assessment Questionnaire (HAQ), the Cochin Hand Functional Scale (CHFS) questionnaire, and the Disability of the Arm, Shoulder, and Hand (DASH) questionnaire; and for HS and pinch strength (2-point tip-to-tip, lateral or key, and 3-point) using Jamar® and pinch gauge dynamometers, respectively. Associations were analyzed by Pearson and Spearman tests, and groups were compared by the independent samples t test, with a significance level of P <  0.05. RESULTS: The convenience sample included 121 rheumatoid patients and a control group matched by age, sex, and body mass index. The RAG showed lower strength values compared with the CG in all measurements (P <  0.01, 95% CI) and these values were associated with worse performance in the functional questionnaires and greater disease activity and duration. There was a strong correlation among the functional assessment instruments. CONCLUSIONS: The decrease in grip and pinch strength, easily measured by portable dynamometers, is a strong indicator of functional disability in RA patients.

Characterization of falls in adults with established rheumatoid arthritis and associated factors.

BACKGROUND: Rheumatoid arthritis patients may have an increased risk of falls due to changes caused by the disease such as muscle weakness, joint impairment, reduced mobility and postural instability. The aim of this study was to prospectively analyze the occurrence of falls in RA patients and its risk factors. METHODS: A cohort of 86 RA patients were assessed over 1 year for disease activity using the Disease Activity Score (DAS-28), for functionality using the Health Assessment Questionnaire (HAQ), for the characterization of falls and for the use of medications, and they were subjected to the Berg Balance Scale (Berg), Timed Up and Go (TUG), 6-Minute Walk (6MWT) and Short Physical Performance Battery (SPPB) tests. The Kolmogorov-Smirnov, Spearman's correlation, Student's t, Mann-Whitney and chi-square tests were performed with a significance level of P ≤ 0.05. RESULTS: A total of 86 patients were evaluated, of which 48.8% had at least one fall and 75.6% reported having a fear of falling. No association of falls with age, disease duration, functional capacity, disease activity or physical performance was found. Patients with poorer performance in the physical tests had more functional impairment, higher disease activity and more advanced age. No differences in physical or functional performance, disease activity, gender or fear of falling were found between fallers and non-fallers; only a greater amount of medications used was found in the group of fallers. CONCLUSIONS: The occurrence of falls was high and associated with a previous history of falls and polypharmacy, with no association with disease activity or duration, functional capacity, physical performance, age or gender.

Correlations of Egen Klassifikation and Barthel Index scores with pulmonary function parameters in Duchenne muscular dystrophy.

PURPOSE: This study investigated the correlations obtained by using the Egen Klassifikation (EK) and Barthel Index (BI) functional scales and respiratory function parameters in patients with Duchenne muscular dystrophy. METHODS: Spirometry, maximal respiratory pressures, and arterial blood gases were analyzed and graded according to the EK and BI scales in 26 patients. They were classified as high or low risk for introduction of noninvasive ventilation according to the respiratory function. RESULTS: The EK and BI scales significantly correlated with forced vital capacity, forced expiratory volume in 1 second, and maximal respiratory pressures. The worse the functional performance, the worse the respiratory measurements. The degree of correlation between the functional scales and each respiratory parameter was similar. An EK of 21 or higher predicted high risk for the introduction of noninvasive ventilation. CONCLUSIONS: EK and BI scales similarly correlated with the degree of respiratory involvement in Duchenne muscular dystrophy. The EK scale was superior in detecting subjects with a higher risk for introduction of noninvasive ventilation.

[Validation of the EK functional motor scale in the Portuguese language]. / Validação da escala motora funcional EK para a língua portuguesa.

OBJECTIVE: To validate a Portuguese version of the EK scale (Egen Klassifikation), that was developed in Denmark for patients with Duchenne muscular dystrophy, and spinal muscular atrophy. METHODS: An English version of the EK scale was translated into the Portuguese language as spoken in Brazil. This scale was applied to 26 male patients (mean age = 12.7 +/- 4.0 years) with Duchenne muscular dystrophy. Patients also answered questions of a Portuguese version of the Barthel index questionnaire, and had their right and left hand grip forces measured with a dynamometer. RESULTS: The mean total EK scale score was 8.1 +/- 7.3 and the Barthel index 54.0 +/- 26.2. The mean hand grip force was 12.7 +/- 17.2 % predicted for the right hand, and 14.6 +/- 19.8 % predicted for the left hand. The EK scale scores showed highly significant statistical correlations with age (r= 0.596, p= 0.0013), right hand grip force (r= -0.556, p= 0.0032), left hand grip force (r= -0.623, p=0.0007), and Barthel index (r= -0.928, p < 0.0001). CONCLUSION: This translated Portuguese version of the EK scale is an adequate tool to be used for Brazilian Duchenne muscular dystrophy patients.

EFFECTS OF VITAMIN C SUPPLEMENTATION ON THE CHRONIC PHASE OF CHAGAS DISEASE.

INTRODUCTION: In order to examine the effectiveness of vitamin C (ascorbic acid) in combating the oxidative insult caused by Trypanosoma cruzi during the development of the chronic phase of Chagas disease, Swiss mice were infected intraperitoneally with 5.0 × 104 trypomastigotes of T. cruzi QM1strain. METHODS: Mice were given supplements of two different doses of vitamin C for 180 days. Levels of lipid oxidation (as indicated by thiobarbituric acid reactive substances-TBARS), total peroxide, vitamin C, and reduced glutathione were measured in the plasma, TBARS, total peroxide and vitamin C were measured in the myocardium and histopathologic analysis was undertaken in heart, colon and skeletal muscle. RESULTS: Animals that received a dose equivalent to 500 mg of vitamin C daily showed increased production of ROS in plasma and myocardium and a greater degree of inflammation and necrosis in skeletal muscles than those that received a lower dose or no vitamin C whatsoever. CONCLUSION: Although some research has shown the antioxidant effect of vitamin C, the results showed that animals subject to a 500 mg dose of vitamin C showed greater tissue damage in the chronic phase of Chagas disease, probably due to the paradoxical actions of the substance, which in this pathology, will have acted as a pro-oxidant or pro-inflammatory.

[Quality of life in adults and elderly patients with rheumatoid arthritis]. / Qualidade de vida de pacientes adultos e idosos com artrite reumatoide.

OBJECTIVE: To analyze and compare quality of life (QoL) in adults and elderly patients with rheumatoid arthritis (RA). METHODS: This was a cross-sectional quantitative study. The tools include the Medical Outcomes Study Short Form-36 (SF-36), the Disease Activity Score 28 (DAS-28), the Assessment Health Questionnaire (HAQ), the Beck Depression Inventory (BDI) and the 6-Minute Walk Test (6MWT). Data analysis was done by descriptive statistics, Student's t test and linear regression test, with significance level of p <0.05. RESULTS: The sample consisted of 99 patients diagnosed with RA, divided into adults and elderly. Those considered adults were 18-59 years-old and those with 60 years or older where considered elderly. In SF-36, the groups showed the pain domain as the most compromised and the emotional aspects domain as the less compromised. Both showed moderate level of disease activity and mild disability. Applying the t test, it was found that there was no significant difference between groups with respect to QoL, functional ability, depression and disease activity. The difference was significant in the 6MWT, in which the elderly achieved an average of 330.8 m, and the adults, 412.2 m (p=0.000). In linear regression, a significant correlation (r=-0.31) between the 6MWT and increasing age was noted. CONCLUSION: QoL and functional capacity in RA were affected in adults and the elderly. How-ever, the results showed no significant difference between groups, with the exception of the 6MWT.

A Brazilian Portuguese version of the Revised Fibromyalgia Impact Questionnaire (FIQR): a validation study.

The Fibromyalgia Impact Questionnaire (FIQ) was specifically developed to assess disease severity and functional ability in fibromyalgia patients. In 2009, a revised version of the FIQ was published, the FIQR; this version achieved a better balance among different domains (function, overall impact, symptoms). Here, we present the validity and reliability of the Brazilian version of the Revised Fibromyalgia Impact Questionnaire (FIQR). Female fibromyalgia patients (n = 106) completed an online survey consisting of the Short Form 36 (SF-36) questionnaire, the original FIQ, and the Brazilian Portuguese FIQR, which was translated by a standard method. Validity was established with correlational analyses between the FIQR, FIQ, and SF-36 items. Three domains were established for the FIQR (function, overall impact, symptoms), and their contribution for the SF-36 subscales was also scrutinized. The Brazilian FIQR validation process showed that the questions performed in a very similar way to the original English FIQR. The new questions in the FIQR symptoms domain (memory, balance, tenderness, and environmental sensitivity) revealed a significant impact in fibromyalgia (FM) patients. The Brazilian Portuguese FIQR demonstrated excellent reliability, with a Cronbach's alpha of 0.96. There was a gain on weight of the function domain and a decrease of the symptom domain, leading to a better balance among domains. The FIQR predicted a great number of SF-36 subscales, showing good convergent validity. The Brazilian Portuguese version of the FIQR was validated and found to be a reliable, easy-to-use, and score FM-specific questionnaire that should prove useful in routine clinical practice and FM-related research.

EpiFibro--a nationwide databank for fibromyalgia syndrome: the initial analysis of 500 women.

INTRODUCTION: Fibromyalgia syndrome (FS) is a common painful condition of the musculoskeletal system that is typically accompanied by several symptoms in other systems. In Brazil, the prevalence of FS is estimated at 2.5%. Here, we present the initial data from Epi-Fibro, a nationwide databank of FS patients seen in public and private settings. OBJECTIVE: The aims of this study were to assess how the diagnosis of FS was made, identify a set of clinical domains considered relevant by both clinicians and patients in cases of FS, analyse the impact of disease on patient quality of life, and compare the findings among patients of public and private services. METHODS: Based on the results of questionnaires, we analysed data corresponding to the first 500 women in the database. Questionnaires pertaining to demographic and clinical data and the Fibromyalgia Impact Questionnaire (FIQ), which was translated and validated for Brazilian patients, were completed by the clinicians and/or patients. RESULTS: Preliminary analysis of the EpiFibro databank revealed that female FS patients in Brazil reported a high impact of disease, as measured by the FIQ, a high prevalence of associated symptoms, and a low degree of education (consistent with the public health care in Brazil used mainly by the underserved). In addition, most patients perceived their pain as diffuse from the onset of disease. CONCLUSION: Depression and anxiety were seen as the main triggers of FM symptoms, but a significant proportion of the subjects perceived work strain as the initial trigger.We also observed a delay of a few years in seeking medical help and examination by a rheumatologist.