The effect of antimalarials on the safety and persistence of treatment with biologic agents or Janus kinase inhibitors in rheumatoid arthritis.

OBJECTIVES: To test the association of use of antimalarials with the overall safety of treatment in RA patients receiving one or multiple courses of biologic (b)DMARDs or a Janus kinase inhibitor (JAKi). METHODS: BiobadaBrasil is a multicentric registry-based cohort study of Brazilian patients with rheumatic diseases starting their first bDMARD or JAKi. The present analysis includes RA patients recruited from January 2009 to October 2019, followed up over one or multiple (up to six) courses of treatment (latest date, 19 November 2019). The primary outcome was the incidence of serious adverse events (SAEs). Total and system-specific adverse events (AEs) and treatment interruption served as secondary outcomes. Negative binomial regression with generalized estimating equations (to estimate multivariate incidence rate ratios, mIRR) and frailty Cox proportional hazards models were used for statistical analyses. RESULTS: The number of patients enrolled was 1316 (2335 treatment courses, 6711 patient-years [PY]; 1254.5 PY on antimalarials). The overall incidence of SAEs was 9.2/100 PY. Antimalarials were associated with reduced risk of SAEs (mIRR: 0.49; 95% CI: 0.36, 0.68; P < 0.001), total AEs (0.68; 95% CI: 0.56, 0.81; P < 0.001), serious infections (0.53; 95% CI: 0.34, 0.84; P = 0.007) and total hepatic AEs (0.21; 95% CI: 0.05, 0.85; P = 0.028). Antimalarials were also related to better survival of treatment course (P = 0.003). There was no significant increase in the risk of cardiovascular AEs. CONCLUSION: Among RA patients on treatment with bDMARDs or JAKi, concomitant use of antimalarials was associated with reduced the incidence of serious and total AEs and with longer treatment course survival.

Development of rapid guidelines: 2. A qualitative study with WHO guideline developers.

BACKGROUND: Situations such as public health emergencies and outbreaks necessitate the development and publication of high-quality recommendations within a condensed timeframe. For example, WHO has produced examples of and guidance for the development of rapid guidelines (RGs). However, more information is needed to understand the experiences and perceptions of guideline developers. This is the second of a series of three articles addressing methodological issues around RGs. This study describes the perceptions and experiences of guideline developers at WHO about RGs. METHODS: We conducted interviews consisting of open- and closed-ended questions with guideline developers at WHO. Our analysis described the definition and rationale of RGs, the differences from regular guidelines with regard to timelines from topic definition until publication, barriers to identifying the evidence and the lack of a standard methodology to develop RGs. RESULTS: We interviewed 10 participants, the majority of whom were comfortable with the current WHO definition of RGs. Most stated that the rationale for developing RGs should be in response to new evidence about efficacy, cost-effectiveness or safety. Respondents differed with regards to the amount of time RGs should take. While the majority of participants agreed that guidelines should be based on a systematic review, this step in the process was considered the most time and resource intensive. Challenges for developing RGs included limited personnel and financial resources as well as the lack of evidence. Facilitators, in turn, that may improve RG development include additional financial and personnel resources as well as the use of virtual meetings. CONCLUSIONS: While our study suggests a strong need and rationale for the development of RGs, standardisation of timelines and guidance on panel composition, peer-review process, conduct of meetings and sources of permissible evidence require further research.

Development of rapid guidelines: 1. Systematic survey of current practices and methods.

BACKGROUND: Guidelines in the healthcare field generally should contain evidence-based recommendations to inform healthcare decisions. Guidelines often require 2 years or more to develop, but certain circumstances necessitate the development of rapid guidelines (RGs) in a short period of time. Upholding methodological rigor while meeting the reduced development timeframe presents a challenge for developing RGs. Our objective was to review current practices and standards for the development of RGs. This is the first of a series of three articles addressing methodological issues around RGs. METHODS: We conducted a systematic survey of methods manuals and published RGs to identify reasons for the development of RGs. Data sources included existing guideline manuals, published RGs, Trip Medical Database, MEDLINE, EMBASE and communication with guideline developers until February 2018. RESULTS: We identified 46 guidelines that used a shortened timeframe for their development. Nomenclature describing RGs varied across organisations, wherein the United States Centers for Disease Control and Prevention produced 'Interim Guidelines', the National Institute for Health and Care Excellence in the United Kingdom developed 'Short Clinical Guidelines', and WHO provided 'Rapid Advice'. The rationale for RGs included response to emergencies, rapid increases in cases of a condition or disease severity, or new evidence regarding treatment. In general, the methods to assess the quality of evidence, the consensus process and the management of the conflict of interest were not always clear. While we identified another 11 RGs from other institutions, there was no reference to timeframe and reasons for conducting a RG. The three organisations mentioned above provide guidance for the development of RGs. CONCLUSIONS: There is a lack of standardised nomenclature and definitions regarding RGs and there is inconsistency in the methods described in manuals and in RG. It is therefore important that all RGs provide a detailed and transparent description of their methods in order for readers and end-users to be able to assess their quality and validate their findings.

Perceptions of the population regarding generic drugs in Brazil: a nationwide survey.

BACKGROUND: Generic drugs (GDs) offer a way to reduce health spending without sacrificing quality. Despite this, there are doubts as to their acceptance by the population. This work aims to assess perceptions of GDs among the Brazilian population. METHODS: We conducted a national household survey face-to-face between April and May 2013, with 5000 individuals aged over 15 years. The questions explored socioeconomic and demographic characteristics, the use of GDs, and perceptions about GDs as compared to brand drugs (BDs). The chi-square test was used to examine the associations between the perceptions and the characteristics of the population. RESULTS: Of the 5000 participants, 51.3% were women, 40.2% were white, 48.6% were between 15 and 34 years of age, and 52.3% had income of less than two minimum wages (US$627.78). In terms of the use of GDs, 44.6% of the participants were taking or had taken GDs in the past three months, with the highest figures among the elderly (61.1%) and female (49.2%) populations. Regarding perceptions, 30.4% of the respondents considered GDs less effective than BDs; provided the same price, 59% would prefer BD, and 45.8% agreed that physicians prefer to prescribe GDs. The most negative perceptions about GDs were observed among lower income, elderly and nonwhite populations. CONCLUSION: The findings provide a better understanding of Brazilians' perceptions regarding GDs. This should be considered when formulating healthcare policies aiming at improving access to effective and quality drugs, and reduction of health costs.

Cross-cultural adaptation and validation of the Brazilian version of the Scleroderma Health Assessment Questionnaire (SHAQ).

The Scleroderma Health Assessment Questionnaire (SHAQ) is a feasible multisystem specific tool that has been extensively used as an additional assessment for systemic sclerosis (SSc). The aim of this study is to cross-culturally adapt and validate the Brazilian version of the SHAQ. Construct validity was assessed based on the correlations between SHAQ and both the Medical Outcomes Survey Short Form 36 version 2 (SF-36v2™) and the Health Assessment Questionnaire Disability Index (HAQ-DI). The correlation between the SHAQ and disease severity was assessed by Spearman's correlation coefficient. The reproducibility of the SHAQ was evaluated by the intraclass correlation coefficient (ICC). Among the 151 consecutive outpatients evaluated, 59 % had limited SSc subtype. The overall disease severity visual analog scale (VAS) of the SHAQ was statistically significantly correlated to HAQ-DI, pain VAS, and the SF-36v2™ physical component summary score (r = 0.595, r = 0.612, and r = -0.582, respectively; p < 0.001). Further analysis of all SF-36v2™ components revealed statistically significant correlations between overall disease severity VAS and bodily pain (r = -0.621, p < 0.001), vitality (r = -0.544, p < 0.001), physical function (r = -0.510, p < 0.001), and role limitation-physical dimensions (r = -0.505, p < 0.001). Moreover, digestive, pulmonary, and overall disease severity VASs were statistically significantly correlated to the number of organs involved (r = 0.178, p = 0.029; r = 0.214, p = 0.008; r = 0.282, p < 0.001). We also demonstrated high reproducibility for SHAQ (ICC = 0.757, 95 % confidence interval = 0.636-0.842). The Brazilian version of the SHAQ demonstrated both construct and discriminant validities as well as good reproducibility.

Developing a provisional definition of flare in patients with established gout.

OBJECTIVE: Various nonvalidated criteria for disease flare have been used in studies of gout. Our objective was to develop empirical definitions for a gout flare from patient-reported features. METHODS: Possible elements for flare criteria were previously reported. Data were collected from 210 gout patients at 8 international sites to evaluate potential gout flare criteria against the gold standard of an expert rheumatologist definition. Flare definitions based on the presence of the number of criteria independently associated with the flare and classification and regression tree approaches were developed. RESULTS: The mean ± SD age of the study participants was 56.2 ± 15 years, 207 of them (98%) were men, and 54 of them (26%) had flares of gout. The presence of any patient-reported warm joint, any patient-reported swollen joint, patient-reported pain at rest score of >3 (0-10 scale), and patient-reported flare were independently associated with the study gold standard. The greatest discriminating power was noted for the presence of 3 or more of the above 4 criteria (sensitivity 91% and specificity 82%). Requiring all 4 criteria provided the highest specificity (96%) and positive predictive value (85%). A classification tree identified pain at rest with a score of >3, followed by patient self-reported flare, as the rule associated with the gold standard (sensitivity 83% and specificity 90%). CONCLUSION: We propose definitions for a disease flare based on self-reported items in patients previously diagnosed as having gout. Patient-reported flare, joint pain at rest, warm joints, and swollen joints were most strongly associated with presence of a gout flare. These provisional definitions will next be validated in clinical trials.

Brazilian version of the foot health status questionnaire (FHSQ-BR): cross-cultural adaptation and evaluation of measurement properties.

OBJECTIVE: To conduct a cross-cultural adaptation of the Foot Health Status Questionnaire into Brazilian-Portuguese and to assess its measurement properties. INTRODUCTION: This instrument is an outcome measure with 10 domains with scores ranging from 0-100, worst to best, respectively. The translated instrument will improve the examinations and foot care of rheumatoid arthritis patients. METHODS: The questions were translated, back-translated, evaluated by a multidisciplinary committee and pre-tested (n = 40 rheumatoid arthritis subjects). The new version was submitted to a field test (n = 65) to evaluate measurement properties such as test-retest reliability, internal consistency and construct validity. The Health Assessment Questionnaire, Numeric Rating Scale for foot pain and Sharp/van der Heijde scores for foot X-rays were used to test the construct validity. RESULTS: The cross-cultural adaptation was completed with minor wording adaptations from the original instrument. The evaluation of measurement properties showed high reliability with low variation coefficients between interviews. The alpha-Cronbach coefficients varied from 0.468 to 0.855, while correlation to the Health Assessment Questionnaire and Numeric Rating Scale was statistically significant for five out of eight domains. DISCUSSION: Intra- and inter-observer correlations showed high reliability. Internal consistency coefficients were high for all domains, revealing higher values for less subjective domains. As for construct validity, each domain revealed correlations with a specific group of parameters according to what the domains intended to measure. CONCLUSION: The FHSQ was cross-culturally adapted, generating a reliable, consistent, and valid instrument that is useful for evaluating foot health in patients with rheumatoid arthritis.

Brazilian version of the foot health status questionnaire (FHSQ-BR): cross-cultural adaptation and evaluation of measurement properties

OBJECTIVE: To conduct a cross-cultural adaptation of the Foot Health Status Questionnaire into Brazilian-Portuguese and to assess its measurement properties. INTRODUCTION: This instrument is an outcome measure with 10 domains with scores ranging from 0-100, worst to best, respectively. The translated instrument will improve the examinations and foot care of rheumatoid arthritis patients. METHODS: The questions were translated, back-translated, evaluated by a multidisciplinary committee and pre-tested (n = 40 rheumatoid arthritis subjects). The new version was submitted to a field test (n = 65) to evaluate measurement properties such as test-retest reliability, internal consistency and construct validity. The Health Assessment Questionnaire, Numeric Rating Scale for foot pain and Sharp/van der Heijde scores for foot X-rays were used to test the construct validity. RESULTS: The cross-cultural adaptation was completed with minor wording adaptations from the original instrument. The evaluation of measurement properties showed high reliability with low variation coefficients between interviews. The a-Cronbach coefficients varied from 0.468 to 0.855, while correlation to the Health Assessment Questionnaire and Numeric Rating Scale was statistically significant for five out of eight domains. DISCUSSION: Intra- and inter-observer correlations showed high reliability. Internal consistency coefficients were high for all domains, revealing higher values for less subjective domains. As for construct validity, each domain revealed correlations with a specific group of parameters according to what the domains intended to measure. CONCLUSION: The FHSQ was cross-culturally adapted, generating a reliable, consistent, and valid instrument that is useful for evaluating foot health in patients with rheumatoid arthritis.

Dialysis care, cardiovascular disease, and costs in end-stage renal disease in Brazil.

OBJECTIVES: This study evaluates the cost of dialysis care in Brazil, including costs of ambulatory care and hospital admissions due to all causes and cardiovascular events. METHODS: Data were analyzed for 200 patients with end-stage renal disease (ESRD) on chronic hemodialysis in Brazil between 2001 and 2004. Main end points were all-cause mortality, all-cause hospital admissions, and cardiovascular events. Direct costs of dialysis treatment and complications were computed from the perspective of two payers, the Ministry of Health (MoH) and private health insurance (PHI). RESULTS: Mean number of days of hospitalization was 12 per patient-year. There were 105 cardiovascular events; the most frequent events were coronary disease (n = 59, 56 percent) and congestive heart failure (n = 26, 25 percent). The rate of cardiovascular events was 193 per 1,000 patient-years. There were 43 deaths, and the death rate was 79 per 1,000 patient-years. Median cost per hospital admission was US$ 675 and US$ 932 from the perspective of the MoH and PHI. For admissions due to cardiovascular causes, the corresponding costs were US$ 1,639 and US$ 4,499, respectively. Mean global cost per patient-year for chronic hemodialysis therapy was US$ 7,980 and US$ 13,428 from the perspective of the MoH and PHI, respectively. CONCLUSIONS: Patients on chronic hemodialysis care incur significant healthcare resources due to the costs of dialysis and complications, notably cardiovascular disease. New disease management programs aimed at reducing cardiovascular morbidity and efficient use of resources are critical to ensuring the sustainability of treatments for ESRD in Brazil.

Lesao immunoproliferativa angiocêntrica: um diagnóstico diferencial com granulomatose de Wegener / Angiocentric immunoproliferative lesion: differential diagnosis with Wegener's granulomatosis

Descreve-se um caso fatal, numa paciente feminina com história de "sinusite crônica" e lesao em bordo interno de olho D desde há quatro meses, que evoluiu com necrose extensa de pele e tecido adjacente dos ossos da face. Apresentava concomitante lesao pulmonar bilateral. O diagnóstico, feito por biópsia profunda da lesao cutânea, foi de lesao imunoproliferativa angiocêntrica, que é o termo atual para designar a granulomatose linfomatóide, o granuloma letal de linha média e o linfoma angiocêntrico. O interesse da apresentaçao desta doença é que ela entra no diagnóstico diferencial das vasculites, particularmente na granulomatose de Wegener