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Objective: The objective was to describe the methodology used to develop new response criteria for adult DM/PM and JDM.Methods: Patient profiles from prospective natural history data and clinical trials were rated by myositis specialists to develop consensus gold-standard ratings of minimal, moderate and major improvement. Experts completed a survey regarding clinically meaningful improvement in the core set measures (CSM) and a conjoint-analysis survey (using 1000Minds software) to derive relative weights of CSM and candidate definitions. Six types of candidate definitions for response criteria were derived using survey results, logistic regression, conjoint analysis, application of conjoint-analysis weights to CSM and published definitions. Sensitivity, specificity and area under the curve were defined for candidate criteria using consensus patient profile data, and selected definitions were validated using clinical trial data.Results: Myositis specialists defined the degree of clinically meaningful improvement in CSM for minimal, moderate and major improvement. The conjoint-analysis survey established the relative weights of CSM, with muscle strength and Physician Global Activity as most important. Many candidate definitions showed excellent sensitivity, specificity and area under the curve in the consensus profiles. Trial validation showed that a number of candidate criteria differentiated between treatment groups. Top candidate criteria definitions were presented at the consensus conference.Conclusion: Consensus methodology, with definitions tested on patient profiles and validated using clinical trials, led to 18 definitions for adult PM/DM and 14 for JDM as excellent candidates for consideration in the final consensus on new response criteria for myositis.

This paper summarizes experiences from long-term ongoing cooperation between Swedish research institutions and institutions at the National Universities in Nicaragua and Costa Rica. 24 researchers and teachers from the Central American institutions and ten Swedish research students have been trained. In addition to three full doctoral and three licentiate (two-year PhD program) theses, the two programs have so far published 15 articles in English-language, international, refereed journals and about three times as many abstracts for conferences in more than ten countries. A "sandwich" model for training is recommended, where the southern researchers come to the wealthier partner for collaborative analyses and write-ups of the publications, while spending 50-75% of their time in their home countries for data collection. Such collaboration should be planned for a time span of at least eight years and include substantial numbers of researchers and students. Means to minimize the risk of brain drain are suggested. The collaboration has been important for the globalization of the research cultures at the participating institutions and has trained international experts.

Neuropsychiatric effects were examined among 206 men, of whom 135 had been house painters and 71 had been house carpenters, affiliated with their respective trade unions for at least 10 years before 1970. Their lifetime organic solvent exposure was evaluated through the aid of an interview. Relevant potential confounding factors were accounted for in the statistical analysis. Neuropsychiatric symptoms compatible with chronic toxic encephalopathy were more common among the painters than among the carpenters, and these symptoms became increasingly prevalent with increasing cumulative solvent exposure. On only one of 12 psychometric tests, block design, did the painters perform worse than the carpenters, and in this test the painters' performance deteriorated with increasing cumulative exposure. For the majority of the psychometric tests, and for the coordination tests, there were no differences between the painters and carpenters, but the painters with "low" exposure tended to show better, and "heavily" exposed painters worse, results than the carpenters. The 52 painters with the heaviest cumulative exposures and 45 carpenters were examined for psychiatric diagnosis according to DSM-III, with electroencephalography and auditory evoked potential, P-300. Three painters and two carpenters had diagnoses compatible with an organic mental disorder. There were no overall differences between the painters and carpenters, either for the visually examined electroencephalograms or the P-300 latencies. The excess of neuropsychiatric symptoms among the painters was probably causally linked to solvent exposure. However, these symptoms seemed only rarely, if ever, serious enough to entail a psychiatric diagnosis. Concerning other outcomes, the investigation may not lead to a determination of whether the exposure-response relationship among the painters, with no difference between the entire group of painters and carpenters, is caused by solvent exposure or by selection factors within the group of painters.

The aim of the present study was to investigate the association between exposure to mineral oil and the risk of developing rheumatoid arthritis (RA), and in addition to perform a separate analysis on the major subphenotypes for the disease; namely, rheumatoid factor (RF)-positive RA, RF-negative RA, anticitrulline-positive RA and anticitrulline-negative RA, respectively. A population-based case-control study of incident cases of RA was performed among the population aged 18-70 years in a defined area of Sweden during May 1996-December 2003. A case was defined as an individual from the study base who for the first time received a diagnosis of RA according to the American College of Rheumatology criteria of 1987. Controls were randomly selected from the study base with consideration taken for age, gender and residential area. Cases (n = 1,419) and controls (n = 1,674) answered an extensive questionnaire regarding lifestyle factors and occupational exposures, including different types of mineral oils. Sera from cases and controls were investigated for RF and anticitrulline antibodies. Among men, exposure to any mineral oil was associated with a 30% increased relative risk of developing RA (relative risk = 1.3, 95% confidence interval = 1.0-1.7). When cases were subdivided into RF-positive RA and RF-negative RA, an increased risk was only observed for RF-positive RA (relative risk = 1.4, 95% confidence interval 1.0-2.0). When RA cases were subdivided according to the presence of anticitrulline antibodies, an increased risk associated with exposure to any mineral oil was observed only for anticitrulline-positive RA (relative risk = 1.6, 95% confidence interval = 1.1-2.2). Analysis of the interaction between oil exposure and the presence of HLA-DR shared epitope genes regarding the incidence of RA indicated that the increased risk associated with exposure to mineral oil was not related to the presence of shared epitope genotypes. In conclusion, our study shows that exposure to mineral oil is associated with an increased risk to develop RF-positive RA and anticitrulline-positive RA, respectively. The findings are of particular interest since the same mineral oils can induce polyarthritis in rats.

T cell abnormalities, B cell hyperactivity and abnormal cytokine production have been implicated to be of pathogenic importance in systemic lupus erythematosus (SLE). The aim of this study was to investigate if ongoing production and serum levels of type 1 and 2 cytokines reflect disease activity and the presence of organ manifestations.Fifty-two SLE patients and 29 healthy individuals were investigated. Blood samples were collected for assessment of anti-ds DNA antibodies, cytokine production and serum cytokine levels. Disease activity was simultaneously assessed using the Systemic Lupus Activity Measure (SLAM) index and SLE Disease Activity Index (SLEDAI). ELISPOT analysis of freshly isolated peripheral blood mononuclear cells (PBMC) was used to estimate the production of cytokines (gamma-interferon (IFN-gamma), interleukin-4 (IL-4), IL-6 and IL-10) using both unstimulated cells and cells stimulated with the T cell mitogen phytohaemagglutinin (PHA). Serum levels of IL-10 were determined using an ELISA method, serum levels of IL-6 were determined using a bioassay and anti-ds DNA antibodies were analysed by immunofluorescence.The SLE patient group had significantly increased numbers of cells spontaneously producing IL-10 and IL-6 as compared to healthy controls (P = 0.01 and 0.03, respectively). The number of cells producing IL-10 and IL-6 after PHA-stimulation was also increased in SLE patients (P = 0.01 and0.0004, respectively). Serum IL-10 and IL-6 levels were also significantly increased in SLE patients (P0.0004 and 0.0005, respectively). Serum IL-10 levels correlated with the titre of anti-ds DNA antibodies in the patients. No correlation was found between disease activity or clinical profiles and the production or serum levels of cytokines except for a weak correlation (not statistically significant) between levels of IL-10 in the sera and disease activity as measured by the SLEDAI but not by the SLAM index.Our results confirm earlier reports that SLE patients have an increased production as well as increased serum levels of the type 2 cytokines IL-10 and IL-6. We found no significant correlation between IL-6 and IL-10 and disease activity or clinical profiles. Serum IL-10 levels correlated with the titre of anti-ds DNA antibodies in the SLE patients. In summary, our result indicate that the increased IL-10 production in SLE could be constitutive.

The purpose of this study was to compare the pattern of mortality of blue-collar workers employed less and more than 1 year in the man-made vitreous fiber (MMVF) and the reinforced plastic industries, the latter group being exposed to styrene. We conducted an analysis among 21,784 workers with less than 1 year of employment (short-term workers) and 19,117 workers with 1 or more years of employment (long-term workers) employed in eight European countries. We conducted analyses based on external as well as internal comparisons. In both cohorts, the standardized mortality ratio for all causes among short-term workers was approximately 40% higher, compared with that for longer-term workers. In internal comparisons, the difference was reduced to 9% in the MMVF cohort and 11% in the styrene cohort. Workers with less than 1 month of employment displayed an increased mortality in both cohorts and in most countries. The increased mortality among short-term workers was not concentrated shortly after they quit employment. In both cohorts, short-term workers had a higher mortality from external causes, while little difference was seen in mortality from ischemic heart disease and malignant neoplasms. Although extra-occupational factors may contribute to increase the mortality of short-term workers and, in particular, of those employed for less than 1 month, the difference observed in analyses adjusted for characteristics of employment suggested a relatively small difference in mortality from most causes.

To study the contribution of the IL10 gene to the susceptibility to systemic lupus erythematosus (SLE).Analysis by fluorescent-semiautomated genotyping of a dinucleotide repeat located in the promoter region of the IL10 locus (microsatellite G).No significant difference was found in the frequencies of the microsatellite alleles of 330 Mexican patients with SLE compared to 368 controls from the same population. Two-point linkage analyses were carried out using 13 Mexican, 13 Swedish, and 8 Icelandic families with 2 or more cases with SLE. No linkage was revealed between IL10 and SLE, using a variety of parameter settings.Our results do not support that the IL10 gene contributes to the susceptibility to SLE in the populations we studied.

Anti-synthetase syndrome (ASSD) is a heterogeneous autoimmune disease characterised by multi-system involvement with a wide variety of manifestations. Validated classification criteria are necessary to improve recognition and prevent misclassification, especially given the lack of reliable and standardised autoantibody testing. We systematically reviewed the literature to analyse proposed ASSD criteria, characteristics, and diagnostic performance. Methods We searched PubMed and Embase databases (01/01/1984 to 06/11/2018) and the ACR and EULAR meeting abstracts (2017-2018). Sensitivities, specificities, positive, negative likelihood ratios and risk of bias were calculated for ASSD criteria and key variables reported in the literature. We performed meta-analysis when appropriate. Results We retrieved 4,358 studies. We found 85 proposed ASSD criteria from a total of 82 studies. All but one study included anti-synthetase autoantibody (ARS) positivity in the ASSD criteria. Most studies required only one ASSD feature plus anti-ARS to define ASSD (n=64, 78%), whereas 16 studies required more than one ASSD variable plus anti-ARS. The only criteria not including anti-ARS positivity required 5 ASSD clinical features. We found limited data and wide variability in the diagnostic performance of each variable and definition proposed in the literature. Given these limitations we only meta-analysed the performance of individual muscle biopsy and clinical variables in diagnosing ASSD, which performed poorly. Conclusion The current ASSD criteria include a variety of serological, clinical, and histological features with wide variability amongst proposed definitions and the performance of these definitions has not been tested. This systematic literature review suggests the need for additional data and consensus-driven classification criteria for ASSD.