Portuguese Authorship in Published Clinical Trials: Differences in Industry and Investigator Initiated Trials.

INTRODUCTION: The aim of this study was to investigate the Portuguese authorship in publications resulting from trials initiated by the industry or investigators and run in Portugal. MATERIAL AND METHODS: Clinical trials with Portuguese institutions as sponsor or recruiting centers, and registered in four clinical trial registries, in the last 14 years, were assessed. Publications of completed trials, from both the initiative of the industry and investigatorswere screened and compared. RESULTS: The percentage of published trials initiated by industry and investigators was similar (28.0%). However, the percentage of completed investigator-initiated trials (43.6%) was lower when compared to industry trials (69.7%). There was a higher percentage of Portuguese authorship in published investigator-initiated trials when compared with industry-initiated trials (47.1% vs 8.5%, respectively). Moreover, industry-initiated trials with Portuguese authors were published in journals with lower journal impact factor when compared with those published without authorship of Portuguese investigators. Oncology was the therapeutic area with the highest number of clinical trial registrations and publications. However, in publications with Portuguese authors, industry Initiated trials mainly focused on neurology while investigator-initiated trials had a higher number of papers in the fields of gastroenterology and infection diseases. Published trials with Portuguese authorship, initiated by the industry or investigators, also targeted different populations and had different purposes. In both cases, no significant differences were observed in terms of the journal impact factor or in the alignment of the published randomized trials with the respective reporting guidelines. DISCUSSION: When compared with previous publications, this study showed an increasing trend in the number of clinical trials in Portugal, published within similar timeframes, after trial conclusion. Even though both industry and investigator trials are published within the standards for reporting trials, the low number of Portuguese authorships in industry publications might underline the need for invigorating these independent clinical trials in Portugal by capacitating and empowering national clinical research teams. CONCLUSION: This study confirmed that even though all registered trials had the involvement of Portuguese institutions as a recruiting center, not all the published trials had Portuguese investigators as authors, mainly those initiated by the industry.

Introdução: Este estudo teve por objetivo investigar a autoria Portuguesa em publicações que resultem de ensaios clínicos iniciados pela indústria e por investigadores, que tenham decorrido em Portugal. Material e Métodos: Quatro plataformas de registo de ensaios clínicos foram utilizadas para encontrar ensaios clínicos tendo instituições Portuguesas como promotor ou centro de recrutamento nos últimos 14 anos. Foram analisadas e comparadas as publicações dos estudos completos, da iniciativa da indústria e de investigadores Resultados: A percentagem de ensaios da iniciativa da indústria e de investigadores que são publicados era semelhante (~ 28,0%). Porém, a percentagem de ensaios completos da iniciativa de investigadores era mais baixa (43,6%) quando comparada com os ensaios completos da indústria (69,7%). Existiu uma maior percentagem de autores portugueses em ensaios publicados da iniciativa do investigador quando comparado com os ensaios da iniciativa da indústria (47,1% vs 8,5%). Para além disso, ensaios da iniciativa da indústria com autores portugueses foram publicados em jornais com fatores de impacto inferiores quando comparados com aqueles publicados sem autores portugueses. A oncologia foi a área terapêutica com maior número de ensaios registados e publicados. No entanto, em publicações com autores Portugueses, a indústria focou-se sobretudo na neurologia e os investigadores em gastroenterologia e doenças infeciosas. Ensaios publicados com autores portugueses, iniciados tanto pela indústria como por investigadores, focaram-se em populações diferentes e têm propósitos diferentes. Em ambos os casos, não foram encontradas diferenças estatisticamente significativas no fator de impacto dos jornais, nem no alinhamento dos ensaios aleatorizados publicados com as normas sobre escrita de artigos científicos. Discussão: Quando comparado com publicações anteriores, este estudo mostrou uma tendência de crescimento no número de ensaios clínicos em Portugal, sendo publicados em intervalos de tempo semelhantes após a sua conclusão. Embora os ensaios publicados da iniciativa da indústria e de investigadores estejam alinhados com as normas sobre escrita de artigos científicos, o baixo número de autorias nacionais em publicações de ensaios da indústria, sublinha a necessidade de revigorar os ensaios clínicos da iniciativa de investigadores através da capacitação e emancipação das equipas de investigação nacionais. Conclusão: Apesar de todos os ensaios registados terem o envolvimento de instituições portuguesas como centros de recrutamento, nem todos os ensaios têm autores portugueses nas publicações, principalmente aqueles que são iniciados pela indústria.

Obesity and diabetes are associated with disability in women with hand osteoarthritis. Results from the EpiReumaPt nationwide study.

BACKGROUND: Hand osteoarthritis (HOA) is a highly prevalent rheumatic disease that predominates in females and causes pain and loss of functional capacity. Obesity and metabolic syndrome have been previously suggested to associate with the severity of HOA, but clarity on these associations is yet to be achieved. OBJECTIVE: Test the association between obesity and other components of the metabolic syndrome and disability in women with hand osteoarthritis (HOA). DESIGN: Individuals from EpiReumaPt epidemiological community-based study (2011-2013) are representative of the Portuguese population. Women with diagnosis of primary HOA were included. PRIMARY OUTCOME: hand functional status, assessed by Cochin questionnaire. SECONDARY OUTCOMES: hand pain, assessed by visual analogue scale and tender hand joint count (THJ). Explanatory variables: obesity, diabetes mellitus, arterial hypertension and hypercholesterolemia. Possible associations between obesity and the other components of metabolic syndrome with Cochin score, hand pain and THJ were tested in a multivariable linear regression model. Potential confounders considered: age, education level and countrywide distribution. RESULTS: 473 women with primary HOA were included. Forty percent were overweight and 29% obese. Ninety-three (19.8%) participants had diabetes, 261 (55.8%) reported hypertension and 261 (55.9%) hypercholesterolemia. Mean Cochin score was 15.5±14.8, mean pain VAS was 4.7±2.6 and mean THJ 1.4±3. In the multivariable analysis, obesity (ß 4.6 CI 0.7;8.5) and diabetes (ß 4.0 CI 0.4;7.6) were found to significantly associate with HOA functional disability. In addition, diabetes, but not obesity, associated with hand pain. There was no association between obesity or diabetes with THJ. CONCLUSION: In a Portuguese female population with primary HOA, obesity and diabetes mellitus independently associated with a worse hand functional status. These data add to evidence suggesting a role of metabolic factors in the severity of HOA.

CORRELATION STUDY BETWEEN DRUSEN MORPHOLOGY AND FUNDUS AUTOFLUORESCENCE.

PURPOSE: To correlate drusen morphology and outer retinal status with autofluorescence (AF) imaging in patients with intermediate age-related macular degeneration. METHODS: Drusen type and morphology were analyzed using color fundus photography and spectral-domain optic coherence tomography, whereas fundus AF was used for drusen AF evaluation. Additional structural changes on spectral-domain optic coherence tomography, such as disruption of external limiting membrane, ellipsoid zone, and retinal pigment epithelium/Bruch membrane complex, as well as the presence of choroidal hypertransmission at correspondent locations were also evaluated and correlated with fundus AF findings. Spearman's correlation coefficient was used to analyze the correlation between spectral-domain optic coherence tomography morphological characteristics of drusen and AF appearance of the corresponding drusen. Strength of correlation was calculated (r), and a P value < 0.05 was considered statistically significant. RESULTS: Two hundred and twenty-eight drusen from 53 eyes of 53 patients were analyzed, 130 soft drusen (57.02%) and 98 cuticular drusen (42.98%). Sixty percent of the drusen were isoautofluorescent (n = 136), 35% hyperautofluorescent (n = 80), and 5% hypoautofluorescent (n = 12). We found positive correlation between drusen AF and hyperreflective foci (r = 0.4). Outer retinal layers morphology (external limiting membrane and ellipsoid zone status and hypertransmission) also correlates with autofluorescent findings (r = 0.3). CONCLUSION: Multimodal imaging reveals a broad spectrum of ultrastructural changes, which may reflect different stages in the evolution of drusen. Our results suggest that drusen morphological characteristics and autofluorescent findings are correlated but other factors or cofactors may be involved. The described correlations will help us understand new progression biomarkers of nonexudative age-related macular degeneration.

Effectiveness of switching between TNF inhibitors in patients with axial spondyloarthritis: is the reason to switch relevant?

BACKGROUND: To investigate whether the reason to discontinue the first TNF inhibitor (TNFi) affects the response to the second TNFi in axial spondyloarthritis (axSpA). METHODS: Patients with axSpA from the Rheumatic Diseases Portuguese Register (ReumaPt), who discontinued their first TNFi and started the second TNFi between June 2008 and May 2018, were included. Response was assessed by the Ankylosing Spondylitis Disease Activity Score (ASDAS) clinically important improvement (ASDAS-CII), major important improvement (ASDAS-MI), low disease activity (ASDAS-LDA), and inactive disease (ASDAS-ID). The reason for discontinuation of the first TNFi was defined, according to ASDAS-CII as primary failure (no response ≤ 6 months), secondary failure (response ≤ 6 months but lost thereafter), adverse events, and others. The association between the reason for discontinuation of the first TNFi and response to the second TNFi over time was assessed in multivariable generalized equation (GEE) models. RESULTS: In total, 193 patients were included. The reason for discontinuation of the first TNFi did not influence the response to the second TNFi, according to the ASDAS-CII. However, a difference was found with more stringent outcomes, e.g., there was a higher likelihood to achieve ASDAS-ID with the second TNFi for patients discontinuing the first TNFi due to secondary failure (OR 7.3 [95%CI 1.9; 27.7]), adverse events (OR 9.1 [2.5; 33.3]), or other reasons (OR 7.7 [1.6; 37.9]) compared to primary failure. CONCLUSION: Patients with axSpA with secondary failure to their first TNFi, compared to those with primary failure, have a better response to the second TNFi according to stringent outcomes.

Eligibility criteria for biologic disease-modifying antirheumatic drugs in axial spondyloarthritis: going beyond BASDAI.

OBJECTIVES: To compare definitions of high disease activity of the Ankylosing Spondylitis Disease Activity Score (ASDAS) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in selecting patients for treatment with biologic disease-modifying antirheumatic drugs (bDMARDs). METHODS: Patients from Rheumatic Diseases Portuguese Register (Reuma.pt) with a clinical diagnosis of axial spondyloarthritis (axSpA) were included. Four subgroups (cross-tabulation between ASDAS (≥2.1) and BASDAI (≥4) definitions of high disease activity) were compared regarding baseline characteristics and response to bDMARDs at 3 and 6 months estimated in multivariable regression models. RESULTS: Of the 594 patients included, the majority (82%) had both BASDAI≥4 and ASDAS ≥2.1. The frequency of ASDAS ≥2.1, if BASDAI<4 was much larger than the opposite (ie, ASDAS <2.1, if BASDAI≥4): 62% vs 0.8%. Compared to patients fulfilling both definitions, those with ASDAS ≥2.1 only were more likely to be male (77% vs 51%), human leucocyte antigen B27 positive (79% vs 65%) and have a higher C reactive protein (2.9 (SD 3.5) vs 2.1 (2.9)). Among bDMARD-treated patients (n=359), responses across subgroups were globally overlapping, except for the most 'stringent' outcomes. Patients captured only by ASDAS responded better compared to patients fulfilling both definitions (eg, ASDAS inactive disease at 3 months: 61% vs 25% and at 6 months: 42% vs 25%). CONCLUSION: The ASDAS definition of high disease activity is more inclusive than the BASDAI definition in selecting patients with axSpA for bDMARD treatment. The additionally 'captured' patients respond better and have higher likelihood of predictors thereof. These results support using ASDAS≥2.1 as a criterion for treatment decisions.

Performance of referral strategies for spondyloarthritis: a population-based nationwide study.

OBJECTIVES: To evaluate the performance of the referral strategy (RS) for SpA of a nationwide epidemiological study (EpiReumaPt), as compared with previously proposed RSs. METHODS: EpiReumaPt was a three-stage national epidemiologic study. In phase one, 10 661 adult participants were randomly selected and screened for rheumatic and musculoskeletal diseases. In the second phase, positive screenings for ⩾1 rheumatic and musculoskeletal disease plus 20% negative screenings were assessed by a rheumatologist. Finally, three rheumatologists revised all the information and defined the final diagnosis. All participants from phase two were included. Thirteen RS were tested against the SpA diagnosis using several metrics, including sensitivity, specificity, the post-test probability of SpA given a positive RS (positive predictive value) and given a negative RS (1 - negative predictive value). RESULTS: From the total 3877 participants, 92 received a SpA diagnosis [weighted national prevalence: 1.6% (95% confidence interval: 1.2, 2.1)]. Modified versions of the Assessment of SpondyloArthritis international Society-RS and EpiReumaPt-RS were the most sensitive (85% and 72%, respectively) and yielded the lowest post-test probabilities of SpA if negative (0.6% and 0.7%, respectively). Considering the national prevalence (pre-test probability) of SpA (1.6%), a negative screening by these two RSs decreased the probability of SpA substantially (Assessment of SpondyloArthritis international Society: -63%; EpiReumaPt: -56%). Other RSs performed less well in reducing disease probability (range: -6.3%; -37.5%). Overall, the probability of SpA given a positive RS was small (positive predictive value range: 2.2%; 7.6%) and the EpiReumaPt RS yielded the best balance between sensitivity and positive predictive value. CONCLUSION: The proposed EpiReumaPt RS performed the best as a screening tool for SpA in patients from the general population when laboratory and imaging data were not available.

The burden and undertreatment of fragility fractures among senior women.

Using a large population database, we showed that fragility fractures were highly prevalent in senior women and were associated with significant physical disability. However, treatment rates were low because osteoporosis treatment was not prescribed or not agreed to by the majority of women with prevalent fragility fractures. PURPOSE: The purpose of the study is to estimate prevalence of fragility fractures (FF), risk factors, and treatment rates in senior women and to assess impact of FF on physical function and quality of life. METHODS: Women aged 65 years and older from the EpiReumaPt study (2011-2013) were evaluated. Rheumatologists collected data regarding FF, clinical risk factors for fractures, and osteoporosis (OP) treatment. Health-related quality of life (EQ5D) and physical function (HAQ) were analyzed. Peripheral dual-energy X-ray absorptiometry was performed. FF was defined as any self-reported low-impact fracture that occurred after 40 years of age. Prevalence estimates of FF were calculated. RESULTS: Among 3877 subjects evaluated in EpiReumaPt, 884 were senior women. The estimated prevalence of FF was 20.7%. Lower leg was the most frequent fracture site reported (37.8%) followed by wrist (18.6%). Only 7.1% of the senior women reporting a prevalent FF were under treatment for OP, and 13.9% never had treatment. OP treatment was not prescribed in 47.7% of FF women, and 23.4% refused treatment. Age (OR = 2.46, 95% CI 1.11-5.47), obesity (OR = 2.05, 95% CI 1.14-3.70), and low wrist BMD (OR = 2.29; 95% CI 1.20, 4.35; p = 0.012) were positively associated with prevalent FF. A significantly higher proportion of women in the lowest quintile of wrist bone mineral density reported FF (OR = 2.29, 95% CI 1.20-4.35). FF were associated with greater physical disability (ß = 0.33, 95% CI 0.13-0.51) independent of other comorbidities. CONCLUSION: FF was frequently reported among senior women as an important cause of physical disability. However, the prevalence of OP treatment was low, which constitutes a public health problem in this vulnerable group.

Hip shape is symmetric, non-dependent on limb dominance and gender-specific: implications for femoroacetabular impingement. A 3D CT analysis in asymptomatic subjects.

OBJECTIVE: To determine the reference intervals (RefInt) of the quantitative morphometric parameters of femoroacetabular impingement (FAI) in asymptomatic hips with computed tomography (CT) and determine their dependence on age, side, limb dominance and sex. METHODS: We prospectively included 590 patients and evaluated 1111 hips with semi-automated CT analysis. We calculated overall, side- and sex-specific parameters for imaging signs of cam [omega and alpha angle (α°)] and pincer-type morphology [acetabular version (ACvers), lateral centre-edge angle (LCEA) and cranio-caudal coverage]. RESULTS: Hip shape was symmetrical and did not depend on limb dominance. The 95% RefInt limits were sex-different for all cam-type parameters and extended beyond current abnormal thresholds. Specifically, the upper limits of RefInt for α° at 12:00, 1:30 and 3:00 o'clock positions were 56°, 70° and 58°, respectively, and 45° for LCEA. Acetabular morphology varied between age groups, with a trend toward an LCEA/ACvers increase over time. CONCLUSION: Our morphometric measurements can be used to estimate normal hip morphology in asymptomatic individuals. Notably they extended beyond current thresholds used for FAI imaging diagnosis, which was most pronounced for cam-type parameters. We suggest the need to reassess α° RefInt and consider a 60° threshold for the 12:00/3:00 positions and 65-70° for other antero-superior positions. KEY POINTS: • Hip shape is symmetrical regardless of limb dominance. • Pincer/cam morphology is frequent in asymptomatic subjects (20 and 71%, respectively). • LCEA and acetabular version increases with age (5-7° between opposite age groups). • Femoral morphology is stable after physeal closure (in the absence of pathology). • Alpha and omega angle thresholds should be set according to sex.

The Use of Analgesic and Other Pain-Relief Drugs to Manage Chronic Low Back Pain: Results from a National Survey.

OBJECTIVES: To analyze and characterize the intake profile of pain-relief drugs in a population-based study of adults with chronic low back pain (CLBP). METHODS: EpiReumaPt was a cross-sectional Portuguese population-based study (10,661 subjects). Self-reported active CLBP was considered to be low back pain on the day of enrollment and for ≥ 90 days. Prevalence and profile of analgesic intake was characterized among those self-reporting active CLBP, taking into account the intensity of pain and the World Health Organization (WHO) analgesic ladder. We further investigated whether the presence of active CLBP was a factor independently associated with the intake of analgesics (adjusted for potential confounders). RESULTS: Among 1,487 subjects with active CLBP, only 18.7% were using analgesic/pain-relief drugs. Estimated prevalence was anxiolytics, 14.1%; nonsteroidal anti-inflammatory drugs (NSAIDs), 12.3%; antidepressants, 10.1%; analgesic, antipyretics, 6.6%; anticonvulsants, 3.4%; central muscle relaxants, 2.6%; and analgesic opioids, 1.6%. Most subjects with severe pain were in the first step of the WHO analgesic ladder: NSAIDs plus anxiolytics (4.6%), NSAIDs plus antidepressants (3.2%), or NSAIDs plus muscle relaxants (2.5%). The presence of active CLBP was significantly associated with the intake of all therapeutic groups: antidepressants (odds ratio [OR] = 12.56; P < 0.001); centrally acting muscle relaxants (OR = 12.01; P < 0.001); anticonvulsants (OR = 9.27; P < 0.001); anxiolytics, sedatives, and hypnotics (OR = 8.86; P < 0.001); NSAIDs (OR = 8.56; P < 0.001); and analgesic opioids (OR = 8.13; P < 0.001). CONCLUSION: Analgesic/pain-relief drug intake in patients with active CLBP was very low, even for those with severe pain. The WHO analgesic ladder was carefully followed, with an extremely conservative use of analgesic opioids even for those with severe pain.

Assessing quality of life of self-reported rheumatic patients.

The aims of this study were to assess the health-related quality of life (HRQoL) in patients with self-reported rheumatic diseases (RD), to classify self-reported rheumatic patients in groups according to their health state and to explore the associations between health status and sociodemographic variables. Data came from the Portuguese Epidemiologic study of the RD. A sample of the Portuguese population aged 18 or more (n = 10,661) stratified by region and locality dimension was interviewed by trained interviewers and answered a standardized questionnaire that included the SF-36v1, the EQ-5D-3L, medical history, identification of potential rheumatic diseases, sociodemographic characteristics, among others. Descriptive statistics and parametric tests were used to compare HRQoL of respondents with and without RD. Comparisons with normative data from the Portuguese population were also carried out. A cluster analysis was used to classify respondents into homogeneous groups. Regression analyses were used to identify factors associated with HRQoL. Respondents with self-reported RD assigned a lower self-perception to their health status. The burden of disease was observed mainly in physical function, role physical and bodily pain. The EQ-5D-3L dimensions show similar results: the intensity of problems is significantly more evident in respondents with self-reported RD. HRQoL of respondents with self-reported RD is related to sociodemographic variables and is significantly lower when compared with the Portuguese population. Four clusters of homogeneous respondents with self-reported RD were formed and characterized according to a number of variables. Factors associated with HRQoL were identified. In conclusion, suffering from a self-reported RD has a significant impact on self-perceived health status and on the quality of life.

Prevalence of rheumatic and musculoskeletal diseases and their impact on health-related quality of life, physical function and mental health in Portugal: results from EpiReumaPt- a national health survey.

OBJECTIVES: To estimate the national prevalence of rheumatic and musculoskeletal diseases (RMDs) in the adult Portuguese population and to determine their impact on health-related quality of life (HRQoL), physical function, anxiety and depression. METHODS: EpiReumaPt is a national health survey with a three-stage approach. First, 10 661 adult participants were randomly selected. Trained interviewers undertook structured face-to-face questionnaires that included screening for RMDs and assessments of health-related quality of life, physical function, anxiety and depression. Second, positive screenings for ≥1 RMD plus 20% negative screenings were invited to be evaluated by a rheumatologist. Finally, three rheumatologists revised all the information and confirmed the diagnoses according to validated criteria. Estimates were computed as weighted proportions, taking the sampling design into account. RESULTS: The disease-specific prevalence rates (and 95% CIs) of RMDs in the adult Portuguese population were: low back pain, 26.4% (23.3% to 29.5%); periarticular disease, 15.8% (13.5% to 18.0%); knee osteoarthritis (OA), 12.4% (11.0% to 13.8%); osteoporosis, 10.2% (9.0% to 11.3%); hand OA, 8.7% (7.5% to 9.9%); hip OA, 2.9% (2.3% to 3.6%); fibromyalgia, 1.7% (1.1% to 2.1%); spondyloarthritis, 1.6% (1.2% to 2.1%); gout, 1.3% (1.0% to 1.6%); rheumatoid arthritis, 0.7% (0.5% to 0.9%); systemic lupus erythaematosus, 0.1% (0.1% to 0.2%) and polymyalgia rheumatica, 0.1% (0.0% to 0.2%). After multivariable adjustment, participants with RMDs had significantly lower EQ5D scores (ß=-0.09; p<0.001) and higher HAQ scores (ß=0.13; p<0.001) than participants without RMDs. RMDs were also significantly associated with the presence of anxiety symptoms (OR=3.5; p=0.006). CONCLUSIONS: RMDs are highly prevalent in Portugal and are associated not only with significant physical function and mental health impairment but also with poor HRQoL, leading to more health resource consumption. The EpiReumaPt study emphasises the burden of RMDs in Portugal and the need to increase RMD awareness, being a strong argument to encourage policymakers to increase the amount of resources allocated to the treatment of rheumatic patients.

Prevalence and social burden of active chronic low back pain in the adult Portuguese population: results from a national survey.

To determine the prevalence of active chronic low back pain (CLBP) in the adult Portuguese population; to compare the active CLBP population with the population without CLBP; and to explore factors associated with active CLBP. The present study was conducted under the scope of EpiReumaPt a population-based study. Active CLBP was self-reported and considered if present on the day of the interview and for ≥90 days. Prevalence estimates were calculated. Association of active CLBP with quality of life, functional ability and healthcare consumption were evaluated. Factors associated with active CLBP were identified through logistic regression. Among 10.661 EpiReumaPt subjects, 1487 self-reported active CLBP. The prevalence of active CLBP was 10.4 % (95 % CI 9.6; 11.9 %). After adjustment, active CLBP subjects had a higher likelihood for anxiety symptoms (OR 2.77), early retirement due to disease (OR 1.88) and more physician visits (ß = 2.65). Factors significantly and independently associated with the presence of active CLBP were: female gender (OR 1.34), overweight/obesity (OR 1.27), presence of self-reported rheumatic musculoskeletal disease (RMD) (OR 2.93), anxiety symptoms (OR 2.67), age (OR 1.02) and higher number of self-reported comorbidities (OR 1.12). Active CLBP is highly prevalent in the Portuguese population and is associated with disability and with a high consumption of healthcare resources. Female gender, older age, anxiety symptoms, overweight/obesity, the presence of other RMD and the number of comorbidities were independently associated with the presence of active CLBP. These factors should be taken into account when new cohort prospective studies will be developed.

EpiReumaPt- the study of rheumatic and musculoskeletal diseases in Portugal: a detailed view of the methodology.

Rheumatic and musculoskeletal diseases (RMD) are prevalent and leading causes of disability and consumption of healthcare and social resources. EpiReumaPt is a national population-based survey developed by the Portuguese Society of Rheumatology that aimed to estimate the prevalence of RMDs and determine their impact on function, quality of life, mental health and use of healthcare resources. This article describes in detail the design, methodology and planned analyses of EpiReumaPt. Recruitment started in September 2011 and finished in December 2013. This study involved a three-stage approach. The first step was a face-to-face survey performed by trained interviewers at the household of 10,661 subjects who where randomly selected by a stratified multistage sampling. A highly sensitive screening questionnaire for RMDs was used. Secondly, participants who screened positive (64%) for at least one RMD as well as 20% of individuals with a negative screening were invited for assessment by a rheumatologist. In total, 3,877 subjects participated in this second phase, where they were also invited to donate a blood sample to be stored at the Biobanco-IMM. History and physical examination, followed by appropriate laboratory and imaging tests were performed. At the end of the visit, the rheumatologist established a diagnosis. Finally, a team of three experienced rheumatologists reviewed all the clinical data and defined the diagnoses according to previously validated criteria. The EpiReumaPt dataset, containing data from several questionnaires, various clinical measurements and information from laboratory and imaging tests, comprises an invaluable asset for research. The large amount of information collected from each participant and the large number of participants, with a wide age range covering and being representative of the adults from the entire country, makes EpiReumaPt the largest study of RMDs performed in Portugal.

EpiReumaPt: how to perform a national population based study - a practical guide.

BACKGROUND: The aim of this article was to describe and discuss several strategies and standard operating procedures undertaken in the EpiReumaPt study - which was the first Portuguese, national, cross-sectional population-based study of Rheumatic and Musculoskeletal Diseases (RMD). METHODS: The technical procedures, legal issues, management and practical questions were studied, analyzed and discussed with relevant stakeholders. During the 1st phase of EpiReumaPt the coordination team and Centro de Estudos de Sondagens e Opinião (CESOP) worked to recruit and interview 10,661 subjects. The 2nd phase involved the participation of a multidisciplinary team, several local authorities, a specialized vehicle ("mobile unit") and a specific software program for the clinical appointments. The development of specific recruitment strategies improved the participation rate. Blood samples were collected and sent to Biobanco-IMM and to a central lab for immediate measurements. In the 3rd phase the RMD diagnosis were validated by a team of three experienced rheumatologists - clinical data, imaging and lab test results were revised according to previously published classification criteria. CONCLUSION: EpiReumaPt was a nationwide project successfully conducted, which followed critical logistic/coordination and research strategies. EpiReumaPt methodology and coordination could be used as an example for other epidemiologic endeavors and public health policies.

CoReumaPt protocol: the Portuguese cohort of rheumatic diseases.

INTRODUCTION: Rheumatic diseases (RD) are conditions with a variety of clinical manifestations and prognosis influenced by several factors. Cohorts and registries have been already established in some countries and have contributed to important knowledge about the disease course and the long-term outcomes of RD. This paper introduces the CoReumaPt project and sets the first step towards the creation of a prospective cohort study including the main RD occurring in the Portuguese population. CoReumaPt will allow outcomes research of chronic RD and the assessment of factors influencing the development and progression of RD. It will also allow to further evaluate the economic impact and the burden of RD in Portugal. CoReumaPt will be linked to Reuma.pt, the National Register of Rheumatic Diseases from the Portuguese Society of Rheumatology. METHODS: An open cohort will be created, initially composed by the randomly selected population of the crosssectional National Epidemiological Rheumatic Diseases study (EpiReumaPt) and afterwards by other sources, namely through self- and physician's referral. Follow-up with annual self-administered questionnaires will be performed, in order to systematically collect and analyze outcomes of interest, mainly patient-reported outcomes. Data concerning less frequent assessments, such as radiographs and biomarkers, will also be assembled. CONCLUSIONS: CoReumaPt will be a valuable resource for scientific research and will deliver pivotal information to improve public health policies concerning the prevention and the management of RD in Portugal.