Real-world Longterm Effectiveness of Tumor Necrosis Factor Inhibitors in Psoriatic Arthritis Patients from the Rheumatic Diseases Portuguese Register.

OBJECTIVE: To assess longterm effectiveness of tumor necrosis factor inhibitors (TNFi) in patients with psoriatic arthritis (PsA) registered in the Rheumatic Diseases Portuguese Register, exposed to at least 1 TNFi, prospectively followed between 2001 and 2017. METHODS: Kaplan-Meier analysis was performed for first-, second-, and third-line TNFi. Responses included European League Against Rheumatism (EULAR) criteria, Disease Activity Index for Psoriatic Arthritis (DAPSA), minimal disease activity (MDA), and Ankylosing Spondylitis Disease Activity Score (ASDAS) at 3 and 6 months. Baseline predictors of discontinuation and response were studied using Cox and multivariable multinomial/logistic regression models. RESULTS: The 750 patients with PsA showed drug retention of 4.1 ± 3.4 years (followup 5.8 ± 3.8 yrs) for first TNFi. Switching to a second (189 patients) or third (50 patients) TNFi further decreased survival by 1.1 years. Female sex, higher baseline 28-joint count Disease Activity Score, and infliximab were predictors of first TNFi discontinuation. After 6 months of the first TNFi, 48.7% of patients achieved a good EULAR criteria response and 20.9% were in DAPSA remission. There were 11.4% in MDA, and 56.4% had a good ASDAS. Responses to the second TNFi were significantly inferior compared to responses to the first TNFi. Female sex and higher baseline Health Assessment Questionnaire-Disability Index were negatively associated with good EULAR response at 3 months, and obesity decreased the chance of response at 6 months. CONCLUSION: In this study, switching to a second or third TNFi was associated with significantly lower drug survival and response rates for patients with axial and peripheral PsA subtypes. More successful therapeutic approaches will require considering the effect of sex and obesity on TNFi effectiveness.

Low Serum Levels of DKK2 Predict Incident Low-Impact Fracture in Older Women.

There are currently no robust noninvasive markers of fragility fractures. Secreted frizzled related protein-1 (sFRP-1), dickkopf-related protein 1 (DKK1) and DKK2, and sclerostin (SOST) inhibit Wnt signaling and interfere with osteoblast-mediated bone formation. We evaluated associations of serum levels of sFRP-1, DKK1, DKK2, and SOST with incident low-impact fracture and BMD in 828 women aged ≥65 years from EpiDoC, a longitudinal population-based cohort. A structured questionnaire during a baseline clinical appointment assessed prevalent fragility fractures and clinical risk factors (CRFs) for fracture. Blood was collected to measure serum levels of bone turnover markers and Wnt regulators. Lumbar spine and hip BMD were determined by DXA scanning. Follow-up assessment was performed through a phone interview; incident fragility fracture was defined by any new self-reported low-impact fracture. Multivariate Cox proportional hazard models were used to analyze fracture risk adjusted for CRFs and BMD. During a mean follow-up of 2.3 ± 1.0 years, 62 low-impact fractures were sustained in 58 women. A low serum DKK2 level (per 1 SD decrease) was associated with a 1.5-fold increase in fracture risk independently of BMD and CRFs. Women in the two lowest DKK2 quartiles had a fracture incidence rate of 32 per 1000 person-years, whereas women in the two highest quartiles had 14 fragility fractures per 1000 person-years. A high serum sFRP1 level was associated with a 1.6-fold increase in fracture risk adjusted for CRFs, but not independently of BMD. Serum levels of SOST (r = 0.191; p = 0.0025) and DKK1(r = -0.1725; p = 0.011) were correlated with hip BMD, but not with incident fragility fracture. These results indicate that serum DKK2 and sFRP1 may predict low-impact fracture. The low number of incident fractures recorded is a limitation and serum levels of Wnt regulators should be further studied in other populations as potential noninvasive markers of fragility fractures. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Tocilizumab and rituximab have similar effectiveness and are both superior to a second tumour necrosis factor inhibitor in rheumatoid arthritis patients who discontinued a first TNF inhibitor.

OBJECTIVES: To compare the effectiveness of a 2nd TNF inhibitor (TNFi), Tocilizumab (TCZ) and Rituximab (RTX), measured by drug retention and by response rates, in RA patients after discontinuing a first-line TNFi and to clarify the reasons and predictors for discontinuation of a second-line biologic. MATERIAL AND METHODS: Non-interventional prospective study of RA patients exposed to a 2nd TNFi, TCZ or RTX after previous TNFi discontinuation using real-world data from Reuma.pt database. Drug retention was estimated using Kaplan-Meier analysis and Cox models. Crude and LUNDEX adjusted response rates were evaluated at 6 months, 1 and 2 years and reasons for discontinuation were compared according to biologic class. RESULTS: In total, 643 patients were included, 88.8% females, with a mean age of 59.4±12.8 years. Of those, 390 (60.7%) initiated a 2nd TNFi, 147 (22.9%) TCZ and 106 (16.5%) RTX. Drug retention was significantly greater among patients who initiated TCZ (76.4±4.3 months) or RTX (80.8±4.8 months), compared with those who initiated a 2nd TNFi (52.7±2.6 months) (log rank test, p < 0.001). In the adjusted Cox model, hazards of discontinuation were significantly lower for TCZ (HR 0.39, 95% CI 0.23-0.64, p < 0.001) and RTX (HR 0.42, 95% CI 0.25-0.72, p=0.001). Smokers had a significantly higher risk for discontinuation (HR 2.43, 95%CI 1.50-3.95, p < 0.001) as well as patients with higher HAQ at baseline (HR 1.51, 95%CI 1.14-2.00, p=0.004). The proportion of patients in remission or low disease activity according to Clinical Disease Activity Index (CDAI) at 6 months, 1 and 2 years was, respectively, 46.5%/50.0%/61.2% for TNFi, 52.9%/53.6%/ 69.2% for TCZ and 37.7%/48.0%/50.0% for RTX. After LUNDEX adjustment, response rates were, respectively, 33.0%/31.0%/31.8% for 2nd TNFi, 42.8%/41.8%/53.3% for TCZ and 32.0%/39.4%/39.0% for RTX. The main reasons for discontinuation were inefficacy for 2nd TNFi and RTX and adverse events for TCZ (p < 0.001). CONCLUSIONS: Our findings showed a significantly higher drug retention for TCZ and RTX, compared with 2nd TNFi, and similar persistence among TCZ and RTX, in patients who discontinued a first-line TNFi. These data corroborate the notion that switching to a biologic with a different mode of action is more effective than to a second TNFi.

Predictors and causes of first-line biologic agent discontinuation in rheumatoid arthritis: data from Reuma.pt.

OBJECTIVES: To assess the discontinuation of first-line biological treatment and to evaluate the reasons and predictors thereof in patients with rheumatoid arthritis (RA) from daily clinical practice. METHODS: RA patients registered in the Rheumatic Diseases Portuguese Register (Reuma.pt) starting treatment with biologic DMARDs (bDMARDs) were included in this prospective observational study. The main outcome was the time to discontinuation (in years) due to any cause. Discontinuation was defined as a 90-day discontinuation of treatment or the occurrence of any switch to another bDMARD during follow-up. Baseline and time-varying sociodemographic and clinical characteristics were tested as possible predictors of discontinuation using multivariable Cox models. RESULTS: Of the 1,851 RA patients included in the study, 871 (47%) discontinued their first bDMARD. The median overall persistence of the first bDMARD was 5.5 years and the leading cause of discontinuation was inefficacy [N=476 (55%)], followed by adverse events [N=262 (30%)], other causes [N=69, (8%)] and unknown causes [N=64 (7%)]. Patients with a higher HAQ score (more disability) at baseline were more likely to discontinue their first bDMARD [hazard ratio (HR):1.39 (95% CI: 1.17-1.64)], as were patients with a higher number of comorbidities [HR: 1.17 (1.05-1.29)] and patients starting treatment from 2007 onwards [HR:1.89 (1.5-2.38)]. On the contrary, receiving TNFi bDMARD [HR:0.74 (0.57-0.94)] as opposed to non-TNFi was associated with less discontinuation. Expectedly, the higher the DAS28 during follow-up the higher the likelihood to discontinue bDMARD [HR:1.08 (1.06-1.1)]. No other time-varying predictor was found. CONCLUSION: In the Portuguese RA population, maintenance of first-line bDMARD was shown to be relatively high. Inefficacy was the leading cause of discontinuation. Features found to predict drug discontinuation (e.g. baseline disability) may contribute to inform clinician's decisions in clinical practice.

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 impact of osteoarthritis on early exit from work: results from a population-based study.

BACKGROUND: Osteoarthritis (OA) is a leading cause of pain and disability, which may be a source of productivity losses. The objectives of this study were to describe the impact of OA, namely through pain and physical disability, on early exit from work and to calculate its economic burden. METHODS: We analysed data from the national, cross-sectional, population-based EpiReumaPt study (Sep2011-Dec2013) in which 10,661 individuals were randomly surveyed in order to capture all cases of rheumatic diseases. We used all participants aged 50-64, near the official retirement age, who were clinically validated by experienced rheumatologists (n = 1286), including OA cases. A national database was used to calculate productivity values by gender, age and region, using the human capital approach. The impact of OA on the likelihood of early exit from work and the population attributable fractions used to calculate due economic burden (indirect costs) were obtained at the individual level by logistic regression. All results were based on weighted data. RESULTS: Almost one third of the Portuguese population aged 50-64 had OA (29.7%; men: 16.2% and women: 43.5%) and more than half were out of paid work (51.8%). Only knee OA is associated with early exit from work (OR: 2.25; 95%CI: 1.42-3.59; p = 0.001), whereas other OA locations did not reach any statistical difference. Furthermore, we observed an association between self-reported longstanding musculoskeletal pain (OR: 1.55; 95%CI: 1.07-2.23; p = 0.02) and pain interference (OR: 1.35; 95%CI: 1.13-1.62; p = 0.001) with early exit from work. We also detected a clear relationship between levels of disability, measured by the Health Assessment Questionnaire (HAQ), and the probability of work withdrawal. The estimated annual cost of early exit from work attributable to OA was €656 million (€384 per capita; €1294 per OA patient and €2095 per OA patient out-of-work). CONCLUSIONS: In this study, we observed an association between OA and early exit from work, largely dependent on pain and disability. This relationship translates into a meaningful economic burden amounting to approximately 0.4% of the national Gross Domestic Product (GDP). The high prevalence and the impact of this disabling chronic disease highlight the need to prioritize policies targeting early exit from work in OA.

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.

Dietary Patterns Characterized by High Meat Consumption Are Associated with Other Unhealthy Life Styles and Depression Symptoms.

OBJECTIVE: We aimed to identify dietary patterns (DPs) of Portuguese adults, to assess their socioeconomic, demographic, lifestyle determinants, and to identify their impact on health. DESIGN: EpiDoC 2 study included 10,153 Portuguese adults from the EpiDoC Cohort, a population-based study. In this study, trained research assistants using computer-assisted telephone interview collected socioeconomic, demographic, dietary, lifestyles, and health information from March 2013 to July 2015. Cluster analysis was performed, based on questions regarding the number of meals, weekly frequency of soup consumption, vegetables, fruit, meat, fish, dairy products, and daily water intake. Factors associated with DP were identified through logistic regression models. RESULTS: Two DPs were identified: the "meat dietary pattern" and the "fruit & vegetables dietary pattern." After multivariable adjustment, women (OR = 0.52; p < 0.001), older adults (OR = 0.97; p < 0.001), and individuals with more years of education (OR = 0.96; p = 0.025) were less likely to adopt the "meat dietary pattern," while individuals in a situation of job insecurity/unemployment (OR = 1.49; p = 0.013), Azores island residents (OR = 1.40; p = 0.026), current smoking (OR = 1.58; p = 0.001), daily alcohol intake (OR = 1.46; p = 0.023), and physically inactive (OR = 1.86; p < 0.001) were positively and significantly associated with "meat dietary pattern." Moreover, individuals with depression symptoms (OR = 1.50; p = 0.018) and the ones who did lower number of medical appointments in the previous year (OR = 0.98; p = 0.025) were less likely to report this DP. CONCLUSION: Our results suggest that unhealthy DPs (meat DP) are part of a lifestyle behavior that includes physical inactivity, smoking habits, and alcohol consumption. Moreover, depression symptoms are also associated with unhealthy DPs.

Real-life effectiveness of Golimumab in biologic-naïve patients with rheumatoid arthritis - data from the Rheumatic Diseases Portuguese Register (Reuma.pt).

OBJECTIVES: To assess the effectiveness of subcutaneous Golimumab 50 mg/monthly combined with methotrexate (SC GLM + MTX) over 52 weeks of treatment, in biologic-naïve RA patients, in a multicentre nationwide cohort from the Rheumatic Diseases Portuguese Register (Reuma.pt). METHODS: Data for this observational study was collected from March 2011 to August 2015. Disease activity (DAS28), functional capacity (HAQ) and Patient Global Disease Assessment (PGDA) were measured at baseline and weeks 12, 24 and 52 of treatment. The primary objective was clinical remission over 52 weeks (1 year) and secondary objectives were: functional response and functional remission over 52 weeks, variation of individual components of DAS over time and treatment persistence at week 52. Comparison between baseline variables of subjects with and without clinical remission was performed. The SC GLM + MTX persistence rate was estimated by the Kaplan-Meier analysis. Cox proportional hazard model approach was used to evaluate predictive factors of persistence, response and remission. RESULTS: A total of 109 patients were enrolled in the study: 94 (86.2%) female, mean age 55.5±13.2 years, mean age at diagnosis 45.5±13.5 years, mean age at beginning of treatment with biologic agents 53.1±13.1 years; 78.1% positive for serum rheumatoid factor. All patients were biologic-naïve and had active disease, despite previous treatment with conventional DMARDs. At the time of this analysis, 93 patients had a follow-up time of at least 52 weeks (i.e. started treatment before August 2014). Of this group, 38.3% achieved clinical remission, 91.9% functional response and 35.2% functional remission, over 52 weeks. Treatment persistence was 75.3% at 1 year. Disease activity indices were all statistically significantly lower at 12, 24 and 52 weeks when compared to baseline. Older age at diagnosis was associated to a lower probability of clinical remission (HR= 0.96, p= 0.031) whereas higher C-reactive protein baseline levels were associated with a lower probability of functional response (HR= 0.54; p= 0.026). CONCLUSIONS: Golimumab 50 mg + MTX showed effectiveness in the treatment of patients with active RA, in accordance to what previously observed in clinical trials. A consistent and significant decrease in RA disease activity through 52 weeks of treatment and a significant functional improvement were observed, as well as a high persistence on treatment.

Home-Based Intervention Program to Reduce Food Insecurity in Elderly Populations Using a TV App: Study Protocol of the Randomized Controlled Trial Saúde.Come Senior.

BACKGROUND: The limited or uncertain access to adequate food in elderly people includes not only economic restrictions but also inability of food utilization due to functional or cognitive impairment, health problems, and illiteracy. OBJECTIVE: The aim of this work is to present the protocol of the randomized controlled trial Saúde.Come Senior, an educational and motivational television (TV)-based intervention to promote healthy lifestyles and decrease food insecurity in elderly people. METHODS: A randomized controlled study will be conducted in subjects aged 60 years and older with food insecurity, identified at 17 primary care centers in the Lisboa e Vale do Tejo health region in Lisbon, Portugal. The primary outcome will be the changes in participants' food insecurity score (evaluated by the Household Food Insecurity Scale) at 3 months. Change in other outcomes will be assessed (dietary habits, nutritional status, physical activity, health status, and clinical outcomes). Subjects will be followed over 6 months; the intervention will last 3 months. Data collection will be performed at 3 different time points (baseline, end of intervention at 3 months, and follow-up at 6 months). The intervention is based on an interactive TV app with an educational and motivational program specifically developed for the elderly that has weekly themes and includes daily content in video format: (1) nutrition and diet tips for healthy eating, (2) healthy, easy to cook and low-cost recipes, and (3) physical exercise programs. Furthermore, brief reminders on health behaviors will also be broadcasted through the TV app. The total duration of the study will be 6 months. The intervention is considered to be effective and meaningful if 50% of the individuals in the experimental group have a decrease of 1 point in the food insecurity score, all the remaining being unchanged. We expect to include and randomize 282 (141 experimental and 141 control) elderly with food insecurity. We will recruit a total of 1,128 subjects considering that 50% of the target individuals are food insecure (based on INFOFAMÍLIA Survey) (567) and about 50% of those will adhere to the study (282). RESULTS: The randomized controlled trial with the 12-week home-based intervention with a comprehensive program on healthy eating and physical activity delivery is planned to start recruiting participants at the end of 2017. CONCLUSIONS: This study will assess the efficacy of this innovative tool (Saúde.Come Senior) for disseminating relevant health information, modifying behaviors, and decreasing food insecurity in an easy, low-cost, and massive way.

Effectiveness of early adalimumab therapy in psoriatic arthritis patients from Reuma.pt - EARLY PsA.

Objective To compare outcomes in psoriatic arthritis (PsA) patients initiating adalimumab (ADA), with short- and long-term disease duration and to evaluate the potential effect of concomitant conventional synthetic disease-modifying antirheumatic drugs (csDMARD) or glucocorticoids. Methods Analyses included adult PsA patients registered in the Rheumatic Diseases Portuguese Register (Reuma.pt) between June 2008-June 2016 who received ADA for ≥3 months. Psoriatic Arthritis Response Criteria (PsARC) response, tender and swollen joint count, inflammatory parameters, patient (PtGA) and physician global assessment (PhGA), Disease Activity Score-28 joints (DAS28), and Health Assessment Questionnaire Disability Index (HAQ-DI) were compared between patients with <5 years of disease (early PsA) and those with ≥5 years of disease duration (late PsA). Time to achieving PsARC response was estimated using the Kaplan-Meier method. Results Of 135 PsA patients treated with ADA, 126 had information on disease duration (earlyPsA, n=41). PsARC response was achieved by 72.9% of the patients (88.0% early PsA vs 62.2% late PsA; P=0.022) after 3 months and by 85.4% after 24 months (100% early PsA vs 75.9% late PsA; P=0.044). Early PsA patients achieved significantly less painful joints (2.7 vs 6.7, p=0.006), lower mean C-reactive protein (0.5 mg/dL vs 1.3 mg/dL; P=0.011), and PhGA (18.3 vs 28.1; P=0.020) at 3 months. In the long term, early PsA patients also had fewer swollen joints (0.3 vs 1.7; P=0.030) and lower PhGA (6.3 vs 21.9; P<0.001), C-reactive protein (0.4 mg/dL vs 1.0 mg/dL; P=0.026), and DAS28 (2.2 vs 3.2; P=0.030). HAQ-DI decreased in both groups reaching a mean value at 24 months of 0.4 and 0.8 (P=ns) in early and late PsA, respectively. Early PsA patients obtained PsARC response more rapidly than late PsA (3.8 and 7.4 months, respectively; P=0.008). Concomitant csDMARDs showed clinical benefit (2-year PsARC response, 88.3% vs 60.0%; P=0.044). Concomitant glucocorticoids had no effect on PsARC response over 2 years of follow-up. Persistence on ADA was similar in both groups. Conclusion Early PsA patients had a greater chance of improvement after ADA therapy and better functional outcome, and achieved PsARC response more rapidly than late PsA. In this cohort, comedication with csDMARDs was beneficial over 2 years.

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.

Juvenile idiopathic arthritis in adulthood: fulfilment of classification criteria for adult rheumatic diseases, long-term outcomes and predictors of inactive disease, functional status and damage.

OBJECTIVES: To determine how adult juvenile idiopathic arthritis (JIA) patients fulfil classification criteria for adult rheumatic diseases, evaluate their outcomes and determine clinical predictors of inactive disease, functional status and damage. METHODS: Patients with JIA registered on the Rheumatic Diseases Portuguese Register (Reuma.pt) older than 18 years and with more than 5 years of disease duration were included. Data regarding sociodemographic features, fulfilment of adult classification criteria, Health Assessment Questionnaire, Juvenile Arthritis Damage Index-articular (JADI-A) and Juvenile Arthritis Damage Index-extra-articular (JADI-E) damage index and disease activity were analysed. RESULTS: 426 patients were included. Most of patients with systemic JIA fulfilled criteria for Adult Still's disease. 95.6% of the patients with rheumatoid factor (RF)-positive polyarthritis and 57.1% of the patients with RF-negative polyarthritis matched criteria for rheumatoid arthritis (RA). 38.9% of the patients with extended oligoarthritis were classified as RA while 34.8% of the patients with persistent oligoarthritis were classified as spondyloarthritis. Patients with enthesitis-related arthritis fulfilled criteria for spondyloarthritis in 94.7%. Patients with psoriatic arthritis maintained this classification. Patients with inactive disease had lower disease duration, lower diagnosis delay and corticosteroids exposure. Longer disease duration was associated with higher HAQ, JADI-A and JADI-E. Higher JADI-A was also associated with biological treatment and retirement due to JIA disability and higher JADI-E with corticosteroids exposure. Younger age at disease onset was predictive of higher HAQ, JADI-A and JADI-E and decreased the chance of inactive disease. CONCLUSIONS: Most of the included patients fulfilled classification criteria for adult rheumatic diseases, maintain active disease and have functional impairment. Younger age at disease onset was predictive of higher disability and decreased the chance of inactive disease.

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.

Assessing transmissibility of HIV-1 drug resistance mutations from treated and from drug-naive individuals.

OBJECTIVES: Surveillance drug resistance mutations (SDRMs) in drug-naive patients are typically used to survey HIV-1-transmitted drug resistance (TDR). We test here how SDRMs in patients failing treatment, the original source of TDR, contribute to assessing TDR, transmissibility and transmission source of SDRMs. DESIGN: This is a retrospective observational study analyzing a Portuguese cohort of HIV-1-infected patients. METHODS: The prevalence of SDRMs to protease inhibitors, nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) in drug-naive and treatment-failing patients was measured for 3554 HIV-1 subtype B patients. Transmission ratio (prevalence in drug-naive/prevalence in treatment-failing patients), average viral load and robust linear regression with outlier detection (prevalence in drug-naive versus in treatment-failing patients) were analyzed and used to interpret transmissibility. RESULTS: Prevalence of SDRMs in drug-naive and treatment-failing patients were linearly correlated, but some SDRMs were classified as outliers - above (PRO: D30N, N88D/S, L90 M, RT: G190A/S/E) or below (RT: M184I/V) expectations. The normalized regression slope was 0.073 for protease inhibitors, 0.084 for NRTIs and 0.116 for NNRTIs. Differences between SDRMs transmission ratios were not associated with differences in viral loads. CONCLUSION: The significant linear correlation between prevalence of SDRMs in drug-naive and in treatment-failing patients indicates that the prevalence in treatment-failing patients can be useful to predict levels of TDR. The slope is a cohort-dependent estimate of rate of TDR per drug class and outlier detection reveals comparative persistence of SDRMs. Outlier SDRMs with higher transmissibility are more persistent and more likely to have been acquired from drug-naive patients. Those with lower transmissibility have faster reversion dynamics after transmission and are associated with acquisition from treatment-failing patients.

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.

A new ensemble coevolution system for detecting HIV-1 protein coevolution.

BACKGROUND: A key challenge in the field of HIV-1 protein evolution is the identification of coevolving amino acids at the molecular level. In the past decades, many sequence-based methods have been designed to detect position-specific coevolution within and between different proteins. However, an ensemble coevolution system that integrates different methods to improve the detection of HIV-1 protein coevolution has not been developed. RESULTS: We integrated 27 sequence-based prediction methods published between 2004 and 2013 into an ensemble coevolution system. This system allowed combinations of different sequence-based methods for coevolution predictions. Using HIV-1 protein structures and experimental data, we evaluated the performance of individual and combined sequence-based methods in the prediction of HIV-1 intra- and inter-protein coevolution. We showed that sequence-based methods clustered according to their methodology, and a combination of four methods outperformed any of the 27 individual methods. This four-method combination estimated that HIV-1 intra-protein coevolving positions were mainly located in functional domains and physically contacted with each other in the protein tertiary structures. In the analysis of HIV-1 inter-protein coevolving positions between Gag and protease, protease drug resistance positions near the active site mostly coevolved with Gag cleavage positions (V128, S373-T375, A431, F448-P453) and Gag C-terminal positions (S489-Q500) under selective pressure of protease inhibitors. CONCLUSIONS: This study presents a new ensemble coevolution system which detects position-specific coevolution using combinations of 27 different sequence-based methods. Our findings highlight key coevolving residues within HIV-1 structural proteins and between Gag and protease, shedding light on HIV-1 intra- and inter-protein coevolution.

The impact of the Lisbon Football Derby on the profile of emergency department admissions.

BACKGROUND: Variations in emergency department admissions have been reported to happen as a result of major sports events. The work presented assessed changes in volume and urgency level of visits to a major Emergency Department in Lisbon during and after the city's football derby. MATERIAL AND METHODS: Volume of attendances and patient urgency level, according to the Manchester Triage System, were retrospectively analyzed for the 2008-2011 period. Data regarding 24-hour periods starting 45 minutes before kick-off was collected, along with data from similar periods on the corresponding weekdays in the previous years, to be used as controls. Data samples were organized according to time frame (during and after the match), urgency level, and paired accordingly. RESULTS: A total of 14 relevant periods (7 match and 7 non-match) were analyzed, corresponding to a total of 5861 admissions. During the match time frame, a 20.6% reduction (p = 0.06) in the total number of attendances was found when compared to non-match days. MTS urgency level sub-analysis only showed a statistically significant reduction (26.5%; p = 0.05) in less urgent admissions (triage levels green-blue). Compared to controls, post-match time frames showed a global increase in admissions (5.6%; p = 0.45), significant only when considering less urgent ones (18.9%; p = 0.05). DISCUSSION: A decrease in the total number of emergency department attendances occurred during the matches, followed by a subsequent increase in the following hours. These variations only reached significance among visits triaged green-blue. CONCLUSION: During major sports events an overall decrease in emergency department admissions seems to take place, especially due to a drop in visits associated with less severe conditions.

IntroduçÉo: Está descrita a ocorrência de variações nas admissões ao serviço de urgência como resultado de eventos desportivos importantes. O estudo que apresentamos avaliou mudanças no volume e tipo de visitas a um serviço de urgência central de Lisboa durante e após o derby futebolístico da cidade.Material e Métodos: Analisámos retrospectivamente o volume de admissões e a categoria de urgência atribuída pela Triagem de Manchester, de 2008 a 2011. Recolhemos dados relativos a períodos de 24 horas com início 45 minutos antes dos jogos, assim como dados relativos a períodos semelhantes nos dias da semana correspondentes dos anos anteriores, para controlo. Organizaram-se os dados por espaços temporais (durante e pós-jogo) e categoria de urgência, após o que se emparelharam.Resultados: Analisaram-se 14 períodos (sete com jogo e sete sem jogo) e um total de 5861 admissões. Durante o jogo verificou-se uma reduçÉo de 20,6% (p = 0,06) no número total de admissões face aos dias controlo. Na sub-análise das categorias da Triagem de Manchester a reduçÉo foi estatisticamente significativa (26,5%; p = 0,05) apenas nas admissões menos urgentes (categorias verdeazul). Comparado com o controlo, o pós-jogo mostrou um aumento global do número de admissões (5,6%; p = 0,45), significativo somente quando consideradas as menos urgentes (18,9%; p = 0,05).DiscussÉo: Durante os jogos o número total de admissões ao serviço de urgência sofreu um decréscimo, ocorrendo nas horas subsequentes um aumento das mesmas. Estas variações só foram significativas nas categorias de triagem verde-azul.ConclusÉo: Durante eventos desportivos importantes parece dar-se uma reduçÉo nas admissões ao serviço de urgência, sobretudo devido a uma diminuiçÉo das visitas associadas a situações menos graves.