Objective To evaluate fenebrutinib, an oral and highly selective noncovalent inhibitor of Bruton's tyrosine kinase (BTK), in patients with active rheumatoid arthritis (RA). Methods Patients with RA and an inadequate response to methotrexate (MTX) (cohort 1; n = 480) were randomized to receive fenebrutinib (50 mg once daily, 150 mg once daily, or 200 mg twice daily), adalimumab (40 mg every other week), or placebo. Patients with RA and an inadequate response to tumor necrosis factor inhibitors (cohort 2; n = 98) received fenebrutinib (200 mg twice daily) or placebo. Both cohorts continued MTX therapy. Results In cohort 1, the percentages of patients in whom American College of Rheumatology 50% improvement criteria (ACR50) was achieved at week 12 were similar in the fenebrutinib 50 mg once daily and placebo groups, and were higher in the fenebrutinib 150 mg once daily group (28%) and 200 mg twice daily group (35%) than in the placebo group (15%) (P = 0.016 and P = 0.0003, respectively). Fenebrutinib 200 mg twice daily and adalimumab (36%) were comparable (P = 0.81). In cohort 2, ACR50 was achieved in more patients receiving fenebrutinib 200 mg twice daily (25%) than placebo (12%) (P = 0.072). The most common adverse events in the fenebrutinib groups included nausea, headache, anemia, and upper respiratory tract infections. Fenebrutinib had significant effects on myeloid and B cell biomarkers (CCL4 and rheumatoid factor). Fenebrutinib and adalimumab caused overlapping as well as distinct changes in B cell and myeloid biomarkers. Conclusion Fenebrutinib demonstrates efficacy comparable to adalimumab in patients with an inadequate response to MTX, and safety consistent with existing immunomodulatory therapies for RA. These data support targeting both B and myeloid cells via this novel mechanism for potential efficacy in the treatment of RA.

OBJECTIVE: To develop a simple and easy-to-use tool for identifying osteoporotic women (femoral neck bone mineral density [BMD] Tscores À 2.5) in Latin America. DESIGN:Retrospective study involving review of medical records.SETTING: Osteoporosis clinics in 6 Latin American countries. PATIENTS:Postmenopausal women ages ! 50 in Latin America who had femoral neck BMD measurements. MEASUREMENTS AND MAIN RESULTS:A risk index was developed from 1,547 patients based on least square regression using age, weight, history of fractures, and other variables as predictors for BMD T-score. The final model was simplified by reducing the number of predictors; sensitivity and specificity were evaluated before and after reducing the number of predictors to assess performance of the index. The final model included age, weight, country, estrogen use, and history of fractures as significant predictors for T-score. The resulting scoring index achieved 91% sensitivity and 47% specificity. Simplifying the index by using only age and weight yielded similar performance (sensitivity, 92%; specificity, 45%). Three risk categories were identified based on OsteoRisk, the index using only age and body weight: high-risk patients (index o =À 2; 65.6% were osteoporotic), moderate-risk patients ( À 2o index o =1; 26.7% were osteoporotic), and low-risk patients (index41; 8% were osteoporotic). Similar results were seen in a validation sample of 279 women in Brazil.CONCLUSION: Age and weight alone performed well for predicting the risk of osteoporosis among postmenopausal women. The OsteoRisk is an easy-to-use tool that effectively targets the vast majority of osteoporotic patients in Latin America for evaluation with BMD. Although patients with fracture should automatically be considered for treatment for osteoporosis, and assessment of bone mineral density (BMD) using dual energy x-ray absorptiometry (DXA) is the standard for diagnosing osteoporosis prior to fracture, facilities for DXA measurements remain limited in Latin America and certain other parts of the world, and this poses a serious challenge for diagnosing osteoporosis in patients without prior fracture.Some researchers have examined the relationship between clinical variables and bone mass in the hope of targeting BMD measurements to patients who are more likely to have osteoporosis.14-20 Lydick et al. 17 developed a model that accurately identifies 90% of subjects with low bone mass and 40% of subjects with normal bone mass. Recently, Koh et al. 18 developed an index, the Osteoporosis Self-assessment Tool for Asians (OSTA), for identifying women at increased risk of osteoporosis in a population of Asian patients other than Japanese. The OSTA is based only on age and weight and achieved a sensitivity of 91% for identifying women with osteoporosis; it was further validated in a cohort of Japanese women, with a sensitivity of 98%. 19 The Osteoporosis Self-assessment Tool (OST) was derived from the OSTA by altering the risk category ranges, and performed well in identifying women at...

Localized scleroderma is a rare disease, characterized by sclerotic lesions. A variety of presentations have been described, with different clinical characteristics and specific prognosis. In scleroderma en coup de sabre (LScs) the atrophic lesion in frontoparietal area is the disease hallmark. Skin and subcutaneous are the mainly affected tissues, but case reports of muscle, cartilage, and bone involvement are frequent. These cases pose a difficult differential diagnosis with Parry-Romberg syndrome. Once considered an exclusive cutaneous disorder, the neurologic involvement present in LScs has been described in several case reports. Seizures are most frequently observed, but focal neurologic deficits, movement disorders, trigeminal neuralgia, and mimics of hemiplegic migraines have been reported. Computed tomography and magnetic resonance imaging have aided the characterization of central nervous system lesions, and cerebral angiograms have pointed to vasculitis as a part of disease pathogenesis. In this paper we describe the clinical and radiologic aspects of neurologic involvement in LScs.

The aim of the study was to analyse the gynaecologic history of 150 Brazilian patients with systemic sclerosis (SSc) by comparing the outcome of the pregnancies before and after disease onset and in the two clinical variants of SSc, as well as to assess the effects of the pregnancy on the progress of the disease. A retrospective analysis was carried out of 150 female SSc patients, more than 18 years old, who attended the outpatient clinic of the Unit of Rheumatology of the State University of Campinas. The patients were questioned about the number of pregnancies, deliveries (full-term infants, premature births and twins) and fetal deaths (spontaneous abortions and perinatal deaths). These data were subdivided into pregnancies before and after SSc onset. In those gestations started after disease onset the patients were questioned about the evolution of SSc during the pregnancy. The patients were also asked about dyspareunia and the age at menopause. Thirty-two patients (21 %) had never been pregnant, and only five of them were considered infertile. One hundred and eighteen patients (79%) had a total of 406 pregnancies, with an average of 3.4 per patient; there were 364 pregnancies before and 42 after SSc onset. There were 58 fetal deaths (14% of the pregnancies), 50 of these occurring before and eight after disease onset; 55 were spontaneous abortions and the other three were perinatal deaths. The fertility rate was higher in the limited SSc (3.6) than in the diffuse SSc patients (3.1), although the percentage of fetal deaths and the evolution of SSc during the pregnancy were similar in the two clinical variants. In the pregnancies that occurred after the onset of SSc, the clinical course remained stable in 72% of the cases, worsened in 14% and improved in 14%. Dyspareunia was mentioned by 49 patients (37% of those with an active sexual life). Menopause was reported by 72 patients, predominantly with limited SSc (61 patients). The fertility rate in the postmenopausal SSc patients was 3.9, similar to that observed in general postmenopausal population in Brazil. The analysis of the gynaecologic history in this series of SSc patients showed no increased risk in infertility or spontaneous abortions. The fertility rate in the two SSc clinical variants was higher than that observed in the local global population. Most of the patients who became pregnant after the onset of SSc showed no signs of worsening during the course of the disease.

Septic arthritis demands early diagnosis and correct treatment if the function of the joint is to be restored. Sometimes, as in fungal infection, signs and symptoms may be mild and the diagnosis delayed. Nevertheless, the outcome of fungal arthritis is severe and usually causes joint disability. The authors report two patients with chronic monoarthritis due to Sporothrix schenckii infection diagnosed by synovial fluid cultures. Their clinical presentation, laboratory and image findings, and their treatment and follow-up are analyzed and compared to previously reported cases. These cases illustrate the differential diagnosis of monoarthritis in immunocompetent adults and picture clinical features that could lead to early diagnosis and proper treatment.

Foot orthoses were effective for improving balance and for reducing pain and disability in elderly women. Orthoses can be used as an adjuvant strategy to improve balance and to prevent falls in the elderly.

OBJECTIVES:To determine whether kidney disease and hemolysis are associated with bone mass density in a population of adult Brazilian patients with sickle cell disease. INTRODUCTION:Bone involvement is a frequent clinical manifestation of sickle cell disease, and it has multiple causes; however, there are few consistent clinical associations between bone involvement and sickle cell disease.METHODS:Patients over 20 years of age with sickle cell disease who were regularly followed at the Hematology and Hemotherapy Center of Campinas, Brazil, were sorted into three groups, including those with normal bone mass density, those with osteopenia, and those with osteoporosis, according to the World Health Organization criteria. The clinical data of the patients were compared using statistical analyses.RESULTS:In total, 65 patients were included in this study: 12 (18.5%) with normal bone mass density, 37 (57%) with osteopenia and 16 (24.5%) with osteoporosis. Overall, 53 patients (81.5%) had bone mass densities below normal standards. Osteopenia and osteoporosis patients had increased lactate dehydrogenase levels and reticulocyte counts compared to patients with normal bone mass density (p<0.05). Osteoporosis patients also had decreased hemoglobin levels (p<0.05). Hemolysis was significantly increased in patients with osteoporosis compared with patients with osteopenia, as indicated by increased lactate dehydrogenase levels and reticulocyte counts as well as decreased hemoglobin levels. Osteoporosis patients were older, with lower glomerular filtration rates than patients with osteopenia. There was no significant difference between the groups with regard to gender, body mass index, serum creatinine levels, estimated creatinine clearance, or microalbuminuria.CONCLUSION:A high prevalence of reduced bone mass density that was associated with hemolysis was found in this population, as indicated by the high lactate dehydrogenase levels, increased reticulocyte counts and low hemoglobin levels.

-The aim of this study was to assess bone mineral density and vitamin D metabolism in patients on chronic anticonvulsant therapy. Methods: Sixty-nine men, outpatients on chronic anticonvulsant therapy, who had been treated for at least 5 years, were studied, comparing them to thirty healthy controls. Bone mineral density was measured as well as serum levels of calcium, ionized calcium, alkaline phosphatase, PTH, 25-hydroxycholecalciferol and 1,25-dihydroxycholecalciferol. Results: No differences in bone mineral density, serum levels of vitamin D and intact-PTH were observed between patients and controls. Bone mineral density was not associated with chronic anticonvulsant therapy. Conclusion: Those adult patients who were on chronic anticonvulsant therapy and who lived in low latitude regions had normal bone mineral density as well as vitamin D serum levels.KEY WORDS: vitamin D, calcium, anticonvulsant, bone mineral density. Densidade mineral óssea, vitamina D e terapia anticonvulsivanteRESUMO -O objetivo deste estudo foi avaliar a densidade mineral óssea e o metabolismo da vitamina D em usuários crônicos de anticonvulsivantes. Métodos: Foram estudados 69 pacientes ambulatoriais, masculinos, usuários crônicos de anticonvulsivantes por período mínimo de 5 anos e comparados a 30 controles normais. Foram efetuadas as medidas da densidade mineral óssea e dos níveis plasmáticos do cálcio, cálcio iônico, fosfatase alcalina, paratormônio, 25-hidroxi-colecalciferol e 1,25-di-hidroxi-colecalciferol. Resultados: Nenhuma diferença na densidade mineral óssea e nos níveis plasmáticos da vitamina D e paratormônio foram observadas entre os pacientes e os controles. A densidade mineral óssea não se mostrou associada ao uso crônico de anticonvulsivantes. Conclusões: Pacientes adultos, do sexo masculino, usuários crônicos de anticonvulsivantes, residentes em regiões ensolaradas, têm densidade mineral óssea e níveis plasmáticos de vitamina D normais. PALAVRAS-CHAVE: vitamina D, cálcio, anticonvulsivante, densidade mineral óssea.Alterations in calcium, vitamin D and bone tissue metabolism have been associated with the following drugs: phenobarbital, phenytoin, primidone and carbamazepine 1,2 . Alterations in the metabolism of calcium are generally very slight and subclinical, but clear cases of hypocalcemia could occur in 4% to 30% of individuals. The intensity of the clinical symptoms depends on many factors, such as: intake of vitamin D, exposure to the sun, physical activity, other diseases that interfere in vitamin D metabolism, the positive correlation of these manifestations with the type of drug, individual drug dosage, and period of exposure, as well as polytherapy 3,6 .This study, which was conducted to assess bone mineral density and vitamin D metabolism in a sample of the Brazilian epileptic population on chronic anticonvulsant therapy, was motivated by the fact that the intensity of alterations of vitamin D metabolism and bone mass was related not only to the chronic use of anticonvulsants but also to other vari...