Large Brazilian Cohort Research Articles

Perfil epidemiológico da espondiloartrite de início juvenil comparada com a espondiloartrite de início na vida adulta em uma grande coorte brasileira

ObjectiveTo analyze the clinical and epidemiologic characteristics of juvenile‐onset spondyloarthritis (SpA) (< 16 years) and compare them with a group of adult‐onset (≥ 16 years) SpA patients. Patients and methodsProspective, observational and multicentric cohort with 1,424 patients with the diagnosis of SpA according to the European Spondyloarthropathy Study Group (ESSG) submitted to a common protocol of investigation and recruited in 29 reference centers participants of the Brazilian Registry of Spondyloarthritis (RBE – Registro Brasileiro de Espondiloartrites). Patients were divided in two groups: age at onset<16 years (JOSpA group) and age at onset ≥ 16 years (AOSpA group). ResultsAmong the 1,424 patients, 235 presented disease onset before 16 years (16.5%). The clinical and epidemiologic variables associated with JOSpA were male gender (p<0.001), lower limb arthritis (p=0.001), enthesitis (p=0.008), anterior uveitis (p=0.041) and positive HLA‐B27 (p=0.017), associated with lower scores of disease activity (Bath Ankylosing Spondylitis Disease Activity Index – BASDAI; p=0.007) and functionality (Bath Ankylosing Spondylitis Functional Index – BASFI; p=0.036). Cutaneous psoriasis (p<0.001), inflammatory bowel disease (p=0.023), dactylitis (p=0.024) and nail involvement (p=0.004) were more frequent in patients with adult‐onset SpA. ConclusionsPatients with JOSpA in this large Brazilian cohort were characterized predominantly by male gender, peripheral involvement (arthritis and enthesitis), positive HLA‐B27 and lower disease scores.

Impact of patient training patterns on peritonitis rates in a large national cohort study.

Ideal training methods that could ensure best peritoneal dialysis (PD) outcome have not been defined in previous reports. The aim of the present study was to evaluate the impact of training characteristics on peritonitis rates in a large Brazilian cohort. Incident patients with valid data on training recruited in the Brazilian Peritoneal Dialysis Multicenter Study (BRAZPD II) from January 2008 to January 2011 were included. Peritonitis was diagnosed according to International Society for Peritoneal Dialysis guidelines; incidence rate of peritonitis (episodes/patient-months) and time to the first peritonitis were used as end points. Two thousand two hundred and forty-three adult patients were included in the analysis: 59 ± 16 years old, 51.8% female, 64.7% with ≤4 years of education. The median training time was 15 h (IQI 10-20 h). Patients were followed for a median of 11.2 months (range 3-36.5). The overall peritonitis rate was 0.29 per year at risk (1 episode/41 patient-months). The mean number of hours of training per day was 1.8 ± 2.4. Less than 1 h of training/day was associated with higher incidence rate when compared with the intervals of 1-2 h/day (P = 0.03) and >2 h/day (P = 0.02). Patients who received a cumulative training of >15 h had significantly lower incidence of peritonitis compared with <15 h (0.26 per year at risk versus 0.32 per year at risk, P = 0.01). The presence of a caregiver and the number of people trained were not significantly associated with peritonitis incidence rate. Training in the immediate 10 days after implantation of the catheter was associated with the highest peritonitis rate (0.32 per year), compared with training prior to catheter implantation (0.28 per year) or >10 days after implantation (0.23 per year). More experienced centers had a lower risk for the first peritonitis (P = 0.003). This is the first study to analyze the association between training characteristics and outcomes in a large cohort of PD patients. Low training time (particularly <15 h), smaller center size and the timing of training in relation to catheter implantation were associated with a higher incidence of peritonitis. These results support the recommendation of a minimum amount of training hours to reduce peritonitis incidence regardless of the number of hours trained per day.

Effectiveness of first-line antiretroviral therapy in the IPEC cohort, Rio de Janeiro, Brazil.

BackgroundWhile Brazil has had a long-standing policy of free access to antiretroviral therapy (ART) for all in need, the epidemiological impact of ART on human immunodeficiency virus (HIV) RNA suppression in this middle-income country has not been well evaluated. We estimate first-line ART effectiveness in a large Brazilian cohort and examine the socio-demographic, behavioral, clinical and structural factors associated with virologic suppression.MethodsVirologic suppression on first-line ART at 6, 12, and 24 months from start of ART was defined as having a viral load measurement ≤400 copies/mL without drug class modification and/or discontinuation. Drug class modification and/or discontinuation were defined based on the class of a particular drug. Quasi-Poisson regression was used to quantify the association of factors with virologic suppression.ResultsFrom January 2000 through June 2010, 1311 patients started first-line ART; 987 (75%) patients used NNRTI-based regimens. Virologic suppression was achieved by 77%, 76% and 68% of patients at 6, 12 and 24 months, respectively. Factors associated with virologic suppression at 12 months were: >8 years of formal education (compared to <4 years, risk ratio (RR) 1.13, 95% confidence interval (95% CI) 1.03-1.24), starting ART in 2005-2010 (compared to 2000-2004, RR 1.25 95% CI 1.15-1.35), and clinical trial participation (compared to no participation, RR 1.08 95% CI 1.01-1.16). Also at 12 months, women showed less virologic suppression compared to heterosexual men (RR 0.90 95% CI 0.82-0.99). For the 24-month endpoint, in addition to higher education, starting ART in the later period, and clinical trial participation, older age and an NNRTI-based regimen were also independently associated with virologic suppression.ConclusionsOur results show that in Brazil, a middle-income country with free access to treatment, over three-quarters of patients receiving routine care reached virologic suppression on first-line ART by the end of the first year. Higher education, more recent ART initiation and clinical trial participation were associated with improved outcomes both for the 12-month and the 24-month endpoints, suggesting that further studies are needed to understand what aspects relating to these factors lead to higher virologic suppression.

FRI0493 Clinical and Serological Comparative Analysis of Systemic Sclerosis with or without Overlap Syndromes in A Large Brazilian Cohort

BackgroundThere are scarce data comparing clinical and serological features in patients with systemic sclerosis (SSc) and SSc overlap syndromes (SSc-OS) due to the rarity of these associations.ObjectivesTo analyze clinical and...

Further evaluation of the EORTC QLQ-C30 psychometric properties in a large Brazilian cancer patient cohort as a function of their educational status

The European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) is considered a valid instrument for use in Brazil. However, the previous Brazilian validation study included only 30 lung cancer patients and only measured test-retest reliability. The aim of this study was to evaluate the psychometric properties of the EORTC QLQ-C30 in a sample of cancer patients at different educational levels who completed the instrument administered by an interviewer. Data from six prospective studies conducted by the same group of researchers were combined in this study (N = 986). Reliability was assessed using Cronbach's alpha coefficient, all values of which were >0.7, with the exception of cognitive functioning, social functioning, and nausea and vomiting (α = 0.57, α = 0.69, and α = 0.68, respectively). In multi-trait scaling analysis, convergent and divergent validity were considered adequate (validity indices were 91.6 and 97.4%). In general, moderate to strong correlations were found between the subscales of the EORTC QLQ-C30 and its respective dimensions from the WHOQOL-bref, the hospital anxiety and depression scale, and the Edmonton Symptom Assessment System (ESAS) instruments. In addition, the EORTC QLQ-C30 was able to differentiate groups of patients with distinct performance statuses and types of treatment (known-group validation). Statistical analyses were also performed on educational status, yielding similar results. Detailed psychometric property data using the EORTC QLQ-C30 in Brazil are added by this study. In addition, we demonstrated that this instrument is in general reliable and valid regardless of the patient educational level.

Enteropathic arthritis in Brazil: data from the Brazilian registry of spondyloarthritis

Inflammatory bowel diseases (Crohn's disease and ulcerative rectocolitis) have extraint- estinal manifestations 25% of the patients, with the most common one being the entero- pathic arthritis. MethodsProspective, observational, multicenter study with patients from 29 reference cen- ters participating in the Brazilian Registry of Spondyloarthritis (RBE), which incorporates the RESPONDIA (Ibero-American Registry of Spondyloarthritis) group. Demographic and clinical data were collected from 1472 patients and standardized questionnaires for the as- sessment of axial mobility, quality of life, enthesitic involvement, disease activity and func- tional capacity were applied. Laboratory and radiographic examinations were performed. The aim of this study is to compare the clinical, epidemiological, genetic, imaging, treat- ment and prognosis characteristics of patients with enteropathic arthritis with other types of spondyloarthritis in a large Brazilian cohort. ResultsA total of 3.2% of patients were classified as having enteroarthritis, 2.5% had spon- dylitis and 0.7%, arthritis (peripheral predominance). The subgroup of individuals with en- teroarthritis had a higher prevalence in women (P < 0.001), lower incidence of inflammatory axial pain (P < 0.001) and enthesitis (P = 0.004). HLA-B27 was less frequent in the group with enteroarthritis (P = 0.001), even when considering only those with the pure axial form. There was a lower prevalence of radiographic sacroiliitis (P = 0.009) and lower radiographic score (BASRI) (P = 0.006) when compared to patients with other types of spondyloarthritis. They also used more corticosteroids (P < 0.001) and sulfasalazine (P < 0.001) and less non- steroidal anti-inflammatory drugs (P < 0.001) and methotrexate (P = 0.001). ConclusionThere were differences between patients with enteroarthritis and other types of spondyloarthritis, especially higher prevalence of females, lower frequency of HLA-B27, associated with less severe axial involvement.

Artrite enteropática no Brasil: dados do registro brasileiro de espondiloartrites

Inflammatory bowel diseases (Crohn's disease and ulcerative rectocolitis) have extraint- estinal manifestations 25% of the patients, with the most common one being the entero- pathic arthritis. MethodsProspective, observational, multicenter study with patients from 29 reference cen- ters participating in the Brazilian Registry of Spondyloarthritis (RBE), which incorporates the RESPONDIA (Ibero-American Registry of Spondyloarthritis) group. Demographic and clinical data were collected from 1472 patients and standardized questionnaires for the as- sessment of axial mobility, quality of life, enthesitic involvement, disease activity and func- tional capacity were applied. Laboratory and radiographic examinations were performed. The aim of this study is to compare the clinical, epidemiological, genetic, imaging, treat- ment and prognosis characteristics of patients with enteropathic arthritis with other types of spondyloarthritis in a large Brazilian cohort. ResultsA total of 3.2% of patients were classified as having enteroarthritis, 2.5% had spon- dylitis and 0.7%, arthritis (peripheral predominance). The subgroup of individuals with en- teroarthritis had a higher prevalence in women (P < 0.001), lower incidence of inflammatory axial pain (P < 0.001) and enthesitis (P = 0.004). HLA-B27 was less frequent in the group with enteroarthritis (P = 0.001), even when considering only those with the pure axial form. There was a lower prevalence of radiographic sacroiliitis (P = 0.009) and lower radiographic score (BASRI) (P = 0.006) when compared to patients with other types of spondyloarthritis. They also used more corticosteroids (P < 0.001) and sulfasalazine (P < 0.001) and less non-steroidal anti-inflammatory drugs (P < 0.001) and methotrexate (P = 0.001). ConclusionThere were differences between patients with enteroarthritis and other types of spondyloarthritis, especially higher prevalence of females, lower frequency of HLA-B27, associated with less severe axial involvement.

Effect of Enthesitis on 1505 Brazilian Patients with Spondyloarthritis

To analyze the clinical effect of enthesitis in a large Brazilian cohort of patients with spondyloarthritis (SpA). A common protocol of investigation was prospectively applied to 1505 patients with SpA in 29 centers in Brazil. Clinical and demographic variables and disease indexes were investigated. The Maastricht Ankylosing Spondylitis Enthesitis Score was used to investigate the enthesitis component. Ankylosing spondylitis was the most frequent disease in the group (65.4%). Others were psoriatic arthritis (18.4%), undifferentiated SpA (6.7%), reactive arthritis (3.3%), and enteropathic arthritis (3.2%). At least 1 affected enthesis was observed in 54% of the patients with SpA, with a mean of 2.12 ± 2.98 entheses affected. According to the clinical presentation, enthesitis was significantly more frequent in patients with axial + peripheral joint involvement compared to isolated axial or peripheral involvement (p < 0.001). There was a statistical association between the presence of enthesites and axial symptoms (buttock pain, cervical pain, and hip pain), and peripheral symptoms (lower limb arthritis, number of painful and swollen joints; p < 0.05). Patients with enthesitis also presented higher mean scores of Bath Ankylosing Spondylitis Functional Index (BASFI; p < 0.001), Bath Ankylosing Spondylitis Disease Activity Index (p < 0.001), and Ankylosing Spondylitis Quality of Life (ASQoL; p < 0.001). Multivariate logistic regression showed that BASFI (p < 0.0001; OR 74.839), ASQoL (p = 0.0001; OR 14.645), and Achilles tendonitis (p = 0.0059; OR 7.593) were associated with work incapacity. The clinical presence of enthesitis in this large cohort of patients with SpA was frequent and was associated with a significant increase in disease activity and decline in functional capacity and quality of life.

Clinical relevance of "bulging eyes" for the differential diagnosis of spinocerebellar ataxias

To investigate the relevance of the clinical finding of bulging eyes (BE) in a large Brazilian cohort of spinocerebellar ataxias (SCA), to assess its importance in clinical differential diagnosis among SCA. Three hundred sixty-nine patients from 168 Brazilian families with SCA were assessed with neurological examination and molecular genetic testing. BE was characterized by the presence of eyelid retraction. Genetically ascertained SCA3 was detected in 167 patients, SCA10 in 68 patients, SCA2 in 20, SCA1 in 9, SCA7 in 6, and SCA6 in 3 patients. BE was detected in 123 patients with SCA (33.3%), namely 109 of the 167 SCA3 patients (65.3%) and in 5 of the others SCA patients (1 SCA10 patient, 2 SCA1 patients and 2 SCA2 patients). BE was detected in the majority of patients with SCA3 (65.3%) and could be used with a clinical tool for the differential diagnosis of SCA.

SAT0281 Impact of enthesitis in 1505 brazilian patients with spondyloarthritis

BackgroundThe spondyloarthritides (SpA) represent a group of chronic diseases that affect around 1% of the population. Enthesitis is a frequent clinical complaint in SpA patients that need to be better...

Systemic sclerosis sine scleroderma: distinct features in a large Brazilian cohort

Systemic sclerosis sine scleroderma (ssSSc) is an infrequent SSc variant characterized by visceral and immunological manifestations of SSc in the absence of clinically detectable skin involvement. We sought to delineate the characteristics of ssSSc in a cohort of Brazilian patients and contrast them with those in the literature. SSc patients seen at two academic medical centres in Brazil were retrospectively analysed. Patients were classified as ssSSc if they presented with RP, positive ANAs and at least one visceral involvement typical of SSc in the absence of skin thickening. Demographics, clinical and laboratory data were obtained by chart review. Literature review was performed by searching available original studies up until June 2012. Among the 947 consecutive patients with SSc, 79 (8.3%) were classified as ssSSc. Oesophagus was the most frequently affected organ (83.1%), followed by pulmonary involvement (63.2%). Compared with the limited cutaneous form of SSc, telangiectasia was the only variable significantly different after multivariate logistic regression analyses (odds ratio 0.46; 95% CI 0.27, 0.81). Compared with the diffuse cutaneous form of SSc, multivariate analyses revealed that ssSSc patients were less likely to be male (odds ratio 0.15; 95% CI 0.04, 0.57), have digital ulcers (odds ratio 0.26; 95% CI 0.13, 0.51) or anti-Scl70 antibodies (odds ratio 0.19; 95% CI 0.07, 0.55) and less frequently treated with CYC (odds ratio 0.23; 95% CI 0.12, 0.43). These features were comparable to those in the published literature. In this series, patients with ssSSc had a relatively mild disease with good prognosis.

Baixa prevalência das manifestações extra-articulares renais, cardíacas, pulmonares e neurológicas nas espondiloartrites: análise do Registro Brasileiro de Espondiloartrites

OBJECTIVE: To describe the extra-articular manifestations (cardiac, renal, pulmonary, and neurological), usually not related to spondyloarthritis (SpA), in a large cohort of Brazilian patients. MATERIALS AND METHODS: This retrospective study analyzed 1,472 patients diagnosed with SpA and cared for at 29 health care centers distributed in the five major geographic regions in the country, participating in the Brazilian Registry of Spondyloarthritis (BRS). All patients were assessed for the prevalence of major extra-articular manifestations (cardiac, renal, pulmonary, and neurological), classified according to the diagnosis [ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis (ReA), arthritis associated with inflammatory bowel disease (IBD), undifferentiated spondyloarthritis (uSpA), and juvenile SpA], and according to the clinical presentation (axial, peripheral, mixed, and enthesitis). RESULTS: Of the patients with SpA assessed, 963 had AS, 271 PsA, 49 ReA, 48 arthritis associated with IBD, 98 uSpA, and 43 juvenile SpA. Cardiac involvement was reported in 44 patients (3.0%), pulmonary involvement in 19 (1.3%), renal involvement in 17 (1.2%), and neurological involvement in 13 patients (0.9%). Most patients with visceral involvement had AS or PsA, and the mixed (axial + peripheral) and/or predominantly axial clinical form. CONCLUSION: Cardiac, renal, pulmonary, and neurological extra-articular manifestations are quite infrequent in SpA, ranging from 0.9% to 3% in this large Brazilian cohort, and affected predominantly patients with AS and PsA.

Are the effects of isoniazid preventive therapy and highly active antiretroviral therapy additive in preventing HIV-associated tuberculosis?

Golub et al. recently reported a retrospective analysis of rates of incident tuberculosis (TB) in a large observational cohort of 2778 patients accessing HIV care in rural and urban South Africa [1]. The TB incidence rate was highest (7.1/100 person-years; 95%CI 6.2–8.2) during the period of care when patients did not receive isoniazid preventive therapy (IPT) or highly active antiretroviral therapy (HAART). The rates were lower during person-time that accrued during follow-up after initiation of IPT (5.2/100 PYs; 95%CI 3.4–7.8) and during follow-up on HAART alone (4.6/100PYs, 95%CI 3.4–6.2). The rate was lower still (1.1/100 PYs 95%CI 0.2–7.6) during person-time accrued during sequential IPT and HAART (IPT+HAART). The authors concluded that TB risk was significantly reduced by IPT in HAART-treated adults. It was further concluded that “the dramatic reduction in TB risk” demonstrated in this study together with supportive data from a similarly analysed study from Brazil [2] indicate that widespread use of IPT should be implemented in conjunction with the roll-out of HAART. Firstly, it is notable that HAART alone but not IPT alone was associated with significantly lower TB incidence rates compared to the non-intervention group in both adjusted and unadjusted analyses. In addition, no significant difference was observed in the incidence rates comparing the HAART only and the IPT+HAART groups. Thus, these analyses do not demonstrate a significant additive effect in TB prevention by treating patients with both IPT and HAART. In further analysis, Kaplan-Meier survival estimates appeared to support a significant difference between TB-free survival in the IPT+HAART group and all other treatment groups. Surprisingly, however, the Kaplan-Meier analysis showed that no TB events occurred among patients in the IPT+HAART group during the first 3 years of observation despite low CD4 cell counts (median, 176 cells/μL at the time of HAART initiation). We are concerned that these conclusions may have been erroneously drawn as a result of analysis of groups with significant selection bias. Among 62 patients within the IPT+HAART group, 61 had initiated IPT a median of 1.0 years (IQR 0.5–1.9) before starting HAART. In this analysis, person-time of observation was censored when patients developed TB. Thus, only selected patients who remained alive and free of TB during the period between IPT initiation and HAART initiation would be eligible for inclusion in the IPT+HAART group. Thus, the TB incidence rate during the median of 1.0 years (IQR 0.5–1.9) of observation before HAART would have been inappropriately assessed as zero cases/100 PYs. However, the IPT-HAART group had markedly lower CD4 cell counts than the IPT alone group and therefore the true incidence rate would very likely have exceeded 5.2 cases/100 PYs in the pre-ART period, potentially adding several more cases to the single case reported in this treatment group. Furthermore, no deaths were reported in this survival analysis and additional cases of TB may have remained unascertained among those who died. Inclusion of such additional TB cases would likely have negated the apparent observed group differences in the Kaplan-Meier analysis. The benefits of IPT in HIV-infected patients included in randomised controlled trials have been clearly demonstrated [3,4]. However, the lack of significant effectiveness of IPT alone in this South African study and in the large Brazilian cohort study [2] raises concerns about the effectiveness of this intervention in routine clinical practice. Potential explanations for lack of IPT efficacy may include poor adherence and the inclusion of TST-negative individuals. However, in both these studies the strongest predictor of TB incidence rates was the baseline CD4 cell count, with 60-90% lower rates in those with CD4 cell strata above 200 cells/uL. Furthermore, there are no data from randomised controlled trials that specifically demonstrate the efficacy of primary IPT at low CD4 cell counts. We wonder therefore whether the inclusion of significant numbers of individuals with CD4 cell counts under 200 cells/uL may partially explain the apparent lack of statistically significant reduction of TB rates during and after IPT. In view of the clear benefits of HAART on survival and TB incidence [5], it would be unethical to perform studies of 6 months IPT or placebo before initiating HAART in eligible patients. TB rates during early HAART are very high and are related to the baseline CD4 cell count at treatment initiation, remain high in those with sub-optimal CD4 cell recovery and continue to be elevated even in those with optimal CD4 cell recovery [7,8,9]. There remains an urgent need to demonstrate an additive benefit of IPT over and above CD4 cell recovery after initiation of HAART and to identify the optimal timing of IPT before this can be scientifically justified as an integrated component of HAART roll-out.