A Stratified Approach for Managing Patients With Low Back Pain in Primary Care (SPLIT Program): A Before-and-After Study.

PURPOSE: To determine the effects of stratified primary care for low back pain (SPLIT program) in decreasing back-related disability for patients with low back pain (LBP) in primary care. METHODS: We conducted a before-and-after study. We compared health-related outcomes for 2 sequential, independent cohorts of patients with LBP recruited at 7 primary care units in Portugal. The first prospective cohort study characterized usual care (UC) and collected data from February to September 2018. The second was performed when the SPLIT program was implemented and collected data from November 2018 to October 2021. Between cohorts, physical therapists were trained in the implementation of the SPLIT program, which used the STarT Back Screening Tool to categorize patients for matched treatment. We compared back-related disability (Roland-Morris Disability Questionnaire, 0-24 points), pain (Numeric Pain Rating Scale, 0-10 points), perceived effect of treatment (Global Perceived Effect Scale, -5 to +5 points), and health-related quality of life (EuroQoL 5 dimensions 3 levels index, 0-1 points). RESULTS: We enrolled a total of 447 patients: 115 in the UC cohort (mostly treated with pharmacologic treatment) and 332 in the SPLIT cohort (all referred for a physical therapy intervention program). Over the study period of 6 months, patients in the SPLIT program showed significantly greater improvements in back-related disability (ß, -2.94; 95% CI, -3.63 to -2.24; P ≤ .001), pain (ß, -0.88; 95% CI, -1.18 to -0.57; P ≤ .001), perceived effect of treatment (ß, 1.40; 95% CI, 0.97 to 1.82; P ≤ .001), and health-related quality of life (ß, 0.11; 95% CI, 0.08 to 0.14; P ≤ .001) compared with UC. CONCLUSIONS: Patients in the SPLIT program for LBP showed greater benefits regarding health-related outcomes than those receiving UC.

Muscle dysfunction in axial spondylarthritis: the MyoSpA study.

OBJECTIVES: We aimed to investigate muscle physical properties, strength, mass, physical performance, and the prevalence of sarcopenia in patients with axial spondylarthritis (axSpA) compared to the healthy controls (HC). METHODS: We performed a cross-sectional study on 54 participants: 27 patients with axSpA and 27 HC, matched by age, gender, and level of physical activity. Muscle physical properties (stiffness, tone and elasticity), muscle strength (five-times sit-to-stand [5STS] test), muscle mass, physical performance (measured through gait speed) and sarcopenia were compared between the groups. Linear regression models were conducted allowing adjustment for relevant variables. RESULTS: Patients with axSpA (mean age 36.5 (SD 7.5) years, 67% males, mean disease duration 6.5 (3.2) years) had no significant difference in segmental muscle stiffness, tone or elasticity, compared with the HC, despite showing a slight numerically higher lower lumbar (L3-L4) stiffness [median 246.5 (IQR 230.5-286.5) vs. 232.5 (211.0-293.5), p=0.38]. No participants presented sarcopenia. Patients with axSpA, compared to the HC, had lower total strength [B=1.88 (95% CI 0.43;3.33)], as well as lower strength in the upper (B=-17.02 (-27.33;-6.70)] and lower limbs [B=-11.14 (-18.25;-4.04)], independently of muscle physical properties. Patients had also significantly lower gait speed than the HC [B=-0.11 (-0.21;-0.01)], adjusted for muscle mass, strength and muscle physical properties. CONCLUSIONS: Young axSpA patients with a relatively short disease duration presented similar segmental muscle physical properties as the HC and had no sarcopenia. Patients with axSpA had reduced physical performance and lower strength compared to the HC, despite normal muscle mass, suggesting a possible muscle dysfunction. Gait characteristics may be a potential biomarker of interest in axSpA.

A Home-Based eHealth Intervention for an Older Adult Population With Food Insecurity: Feasibility and Acceptability Study.

BACKGROUND: Food insecurity is a global public health challenge, affecting predominately the most vulnerable people in society, including older adults. For this population, eHealth interventions represent an opportunity for promoting healthy lifestyle habits, thus mitigating the consequences of food insecurity. However, before their widespread dissemination, it is essential to evaluate the feasibility and acceptability of these interventions among end users. OBJECTIVE: This study aims to explore the feasibility and acceptability of a home-based eHealth intervention focused on improving dietary and physical activity through an interactive television (TV) app among older adults with food insecurity. METHODS: A pilot noncontrolled quasi-experimental study was designed with baseline and 3-month follow-up assessments. Older adult participants with food insecurity were recruited from 17 primary health care centers in Portugal. A home-based intervention program using an interactive TV app aimed at promoting healthy lifestyle behaviors was implemented over 12 weeks. Primary outcomes were feasibility (self-reported use and interest in eHealth) and acceptability (affective attitude, burden, ethicality, perceived effectiveness, and self-efficacy), which were evaluated using a structured questionnaire with a 7-point Likert scale. Secondary outcomes were changes in food insecurity (Household Food Insecurity Scale), quality of life (European Quality of Life Questionnaire with five dimensions and three levels and Functional Assessment of Chronic Illness Therapy-Fatigue), physical function (Health Assessment Questionnaire, Elderly Mobility Scale, grip strength, and regularity of exercise), and nutritional status (adherence to the Mediterranean diet). RESULTS: A sample of 31 older adult individuals with food insecurity was enrolled in the 12-week intervention program with no dropouts. A total of 10 participants self-reported low use of the TV app. After the intervention, participants were significantly more interested in using eHealth to improve food insecurity (baseline median 1.0, IQR 3.0; 3-month median 5.0, IQR 5.0; P=.01) and for other purposes (baseline median 1.0, IQR 2.0; 3-month median 6.0, IQR 2.0; P=.03). High levels of acceptability were found both before and after (median range 7.0-7.0, IQR 2.0-0.0 and 5.0-7.0, IQR 2.0-2.0, respectively) the intervention, with no significant changes for most constructs. Clinically, there was a reduction of 40% in food insecurity (P=.001), decreased fatigue (mean -3.82, SD 8.27; P=.02), and improved physical function (Health Assessment Questionnaire: mean -0.22, SD 0.38; P=.01; Elderly Mobility Scale: mean -1.50, SD 1.08; P=.01; regularity of exercise: baseline 10/31, 32%; 3 months 18/31, 58%; P=.02). No differences were found for the European Quality of Life Questionnaire with five dimensions and three levels, grip strength, or adherence to the Mediterranean diet. CONCLUSIONS: The home-based eHealth intervention was feasible and highly acceptable by participants, thus supporting a future full-scale trial. The intervention program not only reduced the proportion of older adults with food insecurity but also improved participants' fatigue and physical function. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/resprot.6626.

Translation, cross-cultural adaptation and validation of the Osteoarthritis Quality of Life (OAQoL) questionnaire for use in Portugal.

Osteoarthritis (OA) is the most prevalent rheumatic disease and is a leading cause of decreased quality of life (QoL). The OA Quality of Life questionnaire (OAQoL) is an OA-specific patient-reported outcome measures. The aim of this study was to translate and validate the original UK English version of the Osteoarthritis Quality of Life (OAQoL) questionnaire into European Portuguese. The translation of the questionnaire was carried out according to a dual panel methodology (bilingual panel followed by lay panel). This was followed by cognitive debriefing interviews (CDIs) with OA patients to assess comprehension and relevance of the translated questionnaire. Finally, a validation survey was conducted to assess its psychometric properties. The Portuguese OAQoL, a comparator scale (the Nottingham Health Profile-NHP) as well as questions relating to demographic and disease information were administered to OA patients. A sub-sample of patients also completed the Portuguese OAQoL two weeks later, to assess test-retest reliability. The internal consistency, construct validity and known group validity (according to perceived OA severity) of the scale was also assessed. Both the bilingual and lay panels consisted of five individuals and no major difficulties relating to the translation process were identified. A total of ten patients with OA participated in the CDIs. The mean time to complete the questionnaire was 5 min. These interviews revealed that the Portuguese version of the OAQoL was clear, relevant and easy to complete. Finally, 53 OA patients (44 females; mean age of 67.6 years) completed the validation survey. Cronbach's alpha coefficient was 0.87, demonstrating high internal consistency. Test-retest reliability, assessed by Spearman's rank correlation coefficient, was 0.86. Moderate correlations were found with the majority of the NHP sections, providing evidence of construct validity. Significant differences in OAQoL scores were found between patients who differed according to their perceived OA severity, providing evidence of known group validity. The Portuguese version of the OAQoL is a valid and reliable questionnaire that can be used to assess QoL in OA, both in clinical practice and for research purposes.

Radiofrequency echographic multi-spectrometry for the in-vivo assessment of bone strength: state of the art-outcomes of an expert consensus meeting organized by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).

PURPOSE: The purpose of this paper was to review the available approaches for bone strength assessment, osteoporosis diagnosis and fracture risk prediction, and to provide insights into radiofrequency echographic multi spectrometry (REMS), a non-ionizing axial skeleton technique. METHODS: A working group convened by the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis met to review the current image-based methods for bone strength assessment and fracture risk estimation, and to discuss the clinical perspectives of REMS. RESULTS: Areal bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) is the consolidated indicator for osteoporosis diagnosis and fracture risk assessment. A more reliable fracture risk estimation would actually require an improved assessment of bone strength, integrating also bone quality information. Several different approaches have been proposed, including additional DXA-based parameters, quantitative computed tomography, and quantitative ultrasound. Although each of them showed a somewhat improved clinical performance, none satisfied all the requirements for a widespread routine employment, which was typically hindered by unclear clinical usefulness, radiation doses, limited accessibility, or inapplicability to spine and hip, therefore leaving several clinical needs still unmet. REMS is a clinically available technology for osteoporosis diagnosis and fracture risk assessment through the estimation of BMD on the axial skeleton reference sites. Its automatic processing of unfiltered ultrasound signals provides accurate BMD values in view of fracture risk assessment. CONCLUSIONS: New approaches for improved bone strength and fracture risk estimations are needed for a better management of osteoporotic patients. In this context, REMS represents a valuable approach for osteoporosis diagnosis and fracture risk prediction.

Inequity in access to bDMARD care and how it influences disease outcomes across countries worldwide: results from the METEOR-registry.

OBJECTIVE: To establish in a global setting the relationships between countries' socioeconomic status (SES), measured biological disease modifying antirheumatic drug (bDMARD)-usage and disease outcomes. To assess if prescription and reimbursement rules and generic access to medication relates to a countries' bDMARD-usage. METHODS: Data on disease activity and drug use from countries that had contributed at least 100 patients were extracted from the METEOR database. Mean disease outcomes of all available patients at the final visit were calculated on a per-country basis. A questionnaire was sent to at least two rheumatologists per country inquiring about DMARD-prices, access to treatment and valid regulations for prescription and reimbursement. RESULTS: Data from 20 379 patients living in 12 different countries showed that countries' SES was positively associated with measured disease activity (meanDAS28), but not always with physical functioning (HAQ-score). A lower country's SES, stricter rules for prescription and reimbursement of bDMARDs as well as worse affordability of bDMARDs were associated with lower bDMARD-usage. bDMARD-usage was negatively associated with disease activity (although not with physical functioning), but the association was moderate at best. CONCLUSIONS: Disease activity in patients with rheumatoid arthritis as well as bDMARD-usage varies across countries worldwide. The (negative) relationship between countries' bDMARD-usage and level of disease activity is complex and under the influence of many factors, including-but not limited to-countries' SES, affordability of bDMARDs and valid prescription and reimbursement rules for bDMARDs.

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.

Can health care providers recognise a fibromyalgia personality?

OBJECTIVES: To determine if experienced health care providers (HCPs) can recognise patients with fibromyalgia (FM) based on a limited set of personality items, exploring the existence of a FM personality. METHODS: From the 240-item NEO-PI-R personality questionnaire, 8 HCPs from two different countries each selected 20 items they considered most discriminative of FM personality. Then, evaluating the scores on these items of 129 female patients with FM and 127 female controls, each HCP rated the probability of FM for each individual on a 0-10 scale. Personality characteristics (domains and facets) of selected items were determined. Scores of patients with FM and controls on the eight 20-item sets, and HCPs' estimates of each individual's probability of FM were analysed for their discriminative value. RESULTS: The eight 20-item sets discriminated for FM, with areas under the receiver operating characteristic curve ranging from 0.71-0.81. The estimated probabilities for FM showed, in general, percentages of correct classifications above 50%, with rising correct percentages for higher estimated probabilities. The most often chosen and discriminatory items were predominantly of the domain neuroticism (all with higher scores in FM), followed by some items of the facet trust (lower scores in FM). CONCLUSIONS: HCPs can, based on a limited set of items from a personality questionnaire, distinguish patients with FM from controls with a statistically significant probability. The HCPs' expectation that personality in FM patients is associated with higher levels for aspects of neuroticism (proneness to psychological distress) and lower scores for aspects of trust, proved to be correct.

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.

Effectiveness and long-term retention of anti-tumour necrosis factor treatment in juvenile and adult patients with juvenile idiopathic arthritis: data from Reuma.pt.

OBJECTIVES: Assess the effectiveness and safety of biologic therapy as well as predictors of response at 1 year of therapy, retention rate in biologic treatment and predictors of drug discontinuation in JIA patients in the Portuguese register of rheumatic diseases. METHODS: We prospectively collected patient and disease characteristics from patients with JIA who started biological therapy. Adverse events were collected during the follow-up period. Predictors of response at 1 year and drug retention rates were assessed at 4 years of treatment for the first biologic agent. RESULTS: A total of 812 JIA patients [65% females, mean age at JIA onset 6.9 years (s.d. 4.7)], 227 received biologic therapy; 205 patients (90.3%) were treated with an anti-TNF as the first biologic. All the parameters used to evaluate disease activity, namely number of active joints, ESR and Childhood HAQ/HAQ, decreased significantly at 6 months and 1 year of treatment. The mean reduction in Juvenile Disease Activity Score 10 (JADAS10) after 1 year of treatment was 10.4 (s.d. 7.4). According to the definition of improvement using the JADAS10 score, 83.3% respond to biologic therapy after 1 year. Fourteen patients discontinued biologic therapies due to adverse events. Retention rates were 92.9% at 1 year, 85.5% at 2 years, 78.4% at 3 years and 68.1% at 4 years of treatment. Among all JIA subtypes, only concomitant therapy with corticosteroids was found to be univariately associated with withdrawal of biologic treatment (P = 0.016). CONCLUSION: Biologic therapies seem effective and safe in patients with JIA. In addition, the retention rates for the first biologic agent are high throughout 4 years.

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.

Outcomes assessed in trials of gout and accordance with OMERACT-proposed domains: a systematic literature review.

OBJECTIVE: The aim of this study was to systematically review outcome domains and measurement tools used in gout trials and their accordance with the preliminary OMERACT gout recommendations published in 2005. METHODS: Randomized controlled trials (RCTs) and quasi-RCTs investigating any intervention for gout published up to February 2013 were included. Recruitment start dates and all measured outcomes were extracted. Risk of bias (RoB) was assessed with the Cochrane Collaboration tool. Numbers of OMERACT domains were compared for trials at low vs unclear/high RoB and for recruitment start date before 2005 or 2005 and later. RESULTS: Of 9784 articles screened, 38 acute and 30 chronic gout trials were included. Mean (s.d.) number of OMERACT outcomes was 2.9 (1.1) (out of 5) and 2.5 (1.2) (out of 9) for acute and chronic gout trials, respectively. Health-related quality of life, participation and joint damage imaging were not assessed in any trial. Tools used to measure individual domains varied widely. There were no differences in the number of OMERACT outcomes reported in acute or chronic gout trials recruiting before 2005 vs 2005 or later [mean (s.d.): 3.0 (1.1) vs 3.5 (1.3), P = 0.859 and 2.7 (1.1) vs 2.8 (1.4), P = 0.960, respectively]. While both acute and chronic trials at low RoB reported more OMERACT domains than trials at unclear/high RoB, these differences were not significant. Industry-funded trials and trials performed by OMERACT investigators reported more OMERACT outcome domains. CONCLUSION: We found no appreciable impact of the OMERACT recommendations for gout trials to date.

Fibromyalgia characterization in a psychosocial approach.

This study aimed to characterize a group of women diagnosed with fibromyalgia, evaluating the relationship between personality and psychopathology, health status (disability, physical health, mental health, and pain), and potentially traumatic life events (PTLE) before the onset of the syndrome. The disability caused by fibromyalgia, physical and mental health status, pain, PTLE in childhood and in the course of life, and personality were assessed in a sample of 50 women with fibromyalgia, age 25-70 years (M = 46.96; SD = 10.96). A multiple correspondence analysis with all the variables identified two types of profiles and a K-Means cluster analysis confirmed two groups of patients: cluster 1 (n = 36), with better health and less psychopathological problems, named "Better adjustment" and cluster 2 (n = 14), with less health and more personality problems, named "Disorder and disability." Pertaining to personality only, a K-Means cluster analysis replicated the three classic personality profiles (normal, neurotic, and psychopathological) identified in chronic pain patients; and the normal profile was the more prevalent (n = 22). The results enhance the importance of recognizing the heterogeneity of fibromyalgia population and the great closeness between personality and physical health, with the PTLE having a less important role than expected.

Multinational evidence-based recommendations for the diagnosis and management of gout: integrating systematic literature review and expert opinion of a broad panel of rheumatologists in the 3e initiative.

We aimed to develop evidence-based multinational recommendations for the diagnosis and management of gout. Using a formal voting process, a panel of 78 international rheumatologists developed 10 key clinical questions pertinent to the diagnosis and management of gout. Each question was investigated with a systematic literature review. Medline, Embase, Cochrane CENTRAL and abstracts from 2010-2011 European League Against Rheumatism and American College of Rheumatology meetings were searched in each review. Relevant studies were independently reviewed by two individuals for data extraction and synthesis and risk of bias assessment. Using this evidence, rheumatologists from 14 countries (Europe, South America and Australasia) developed national recommendations. After rounds of discussion and voting, multinational recommendations were formulated. Each recommendation was graded according to the level of evidence. Agreement and potential impact on clinical practice were assessed. Combining evidence and clinical expertise, 10 recommendations were produced. One recommendation referred to the diagnosis of gout, two referred to cardiovascular and renal comorbidities, six focused on different aspects of the management of gout (including drug treatment and monitoring), and the last recommendation referred to the management of asymptomatic hyperuricaemia. The level of agreement with the recommendations ranged from 8.1 to 9.2 (mean 8.7) on a 1-10 scale, with 10 representing full agreement. Ten recommendations on the diagnosis and management of gout were established. They are evidence-based and supported by a large panel of rheumatologists from 14 countries, enhancing their utility in clinical practice.

Molecular Profiling of Axial Spondyloarthritis Patients Reveals an Association between Innate and Adaptive Cell Populations and Therapeutic Response to Tumor Necrosis Factor Inhibitors.

This study aims at identifying molecular biomarkers differentiating responders and non-responders to treatment with Tumor Necrosis Factor inhibitors (TNFi) among patients with axial spondyloarthritis (axSpA). Whole blood mRNA and plasma proteins were measured in a cohort of biologic-naïve axSpA patients (n = 35), pre and post (14 weeks) TNFi treatment with adalimumab. Differential expression analysis was used to identify the most enriched pathways and in predictive models to distinguish responses to TNFi. A treatment-associated signature suggests a reduction in inflammatory activity. We found transcripts and proteins robustly differentially expressed between baseline and week 14 in responders. C-reactive protein (CRP) and Haptoglobin (HP) proteins showed strong and early decrease in the plasma of axSpA patients, while a cluster of apolipoproteins (APOD, APOA2, APOA1) showed increased expression at week 14. Responders to TNFi treatment present higher levels of markers of innate immunity at baseline, and lower levels of adaptive immunity markers, particularly B-cells. A logistic regression model incorporating ASDAS-CRP, gender, and AFF3, the top differentially expressed gene at baseline, enabled an accurate prediction of response to adalimumab in our cohort (AUC = 0.97). In conclusion, innate and adaptive immune cell type composition at baseline may be a major contributor to response to adalimumab in axSpA patients. A model including clinical and gene expression variables should also be considered.

Protective effect of an ERAP1 haplotype in ankylosing spondylitis: investigating non-MHC genes in HLA-B27-positive individuals.

OBJECTIVE: The association of non-MHC genes with AS has been recently suggested. We aimed to investigate the association of the ERAP1, IL23R and TNFSF15 regions and the susceptibility to and protection from AS in HLA-B27-positive individuals. METHODS: A total of 200 unrelated AS patients and 559 healthy unrelated subjects, all HLA-B27 positive, were tested. Twenty single nucleotide polymorphisms (SNPs) were investigated in and near IL23R (nine SNPs), in ERAP1 (five SNPs) and in TNFSF15 (six SNPs). RESULTS: ERAP1 rs30187 [odds ratio (OR) = 1.5, P = 4.7 × 10(-3)] had the strongest association with AS susceptibility. A protective effect was found in three of the ERAP1 SNPs: rs17482078 (OR = 0.7, P = 2.8 × 10(-2)), rs10050860 (OR = 0.7, P = 2.3 × 10(-2)), rs2287987 (OR = 0.6, P = 1.3 × 10(-2)). The ERAP1 haplotype rs17482078/rs10050860/rs30187/rs2287987-CCTT showed an association with AS susceptibility (P = 6.8 × 10(-3)) and a protective effect was identified in rs17482078/rs10050860/rs30187/rs2287987-TTCC (P = 3.1 × 10(-2)). Significant association with AS susceptibility was found in one IL23R marker (rs1004819, P = 4.3 × 10(-2), OR = 1.3). No associations were observed in the TNFSF15 region. CONCLUSION: The identification of a new protection haplotype in ERAP1 and the lack of association of the TNFSF15 region can provide new insights into the understanding of the mechanisms underlying the susceptibility to and protection from AS.

Fibromyalgia: antecedent life events, disability, and causal attribution.

This study aimed to evaluate the relation of disability and physical and mental health status with potentially traumatic life events (PTLE) before the onset of fibromyalgia in women diagnosed with this syndrome. We also investigated causal attribution of fibromyalgia to a triggering event, physical or psychological in nature, and its relation with the health measures and the adverse life events. The impact of fibromyalgia, physical and mental health status, pain, PTLE in childhood and not in childhood, and causal attribution were assessed in a sample of 50 women with fibromyalgia, aged 25-70 (M = 46.96; SD = 10.96). There were no statistically significant relations between the health measures (disability, physical and mental health, and pain) and the PTLE. The predominant attribution was to a physical event. There were no significant differences neither in the health measures across causal attribution status (Pillai's Trace = 0.193; F(8,90) = 1.200; p = .308; η2 par = .096) nor in the PTLE not in childhood (F(2,47) = 1.063; p = .354; η2 par = .043). There were significant differences across causal attribution status in the PTLE in childhood (F(2,47) = 3.590; p = .035; η2 par = .133), specifically between the group that made a psychological attribution and the group that made no attribution (C.I. 95%) 0.1805; 14.0468; (p = .043), with the former having a higher score of PTLE in childhood. The results raise questions about the importance of psychological aspects in the appraisal of the adverse events and its possible relation to the psychological functioning in women with fibromyalgia.

Drug-induced accelerated nodulosis: review of the literature.

Accelerated nodulosis, the rapid progression/extension of preexisting nodules, is a recognized complication of immunomodulatory therapy, occurring mostly in patients with rheumatoid arthritis treated with methotrexate. As of today, its physiopathology remains incompletely understood, and there are no standardized guidelines regarding its management. Here, we conduct a literature review of the reported cases of drug-induced accelerated nodulosis and add our case of a 79-year-old female with an atypical clinical presentation.

Clinical courses, impact and prognostic indicators for a persistent course of low back pain: Results from a population-based cohort study.

BACKGROUND: Low back pain (LBP) is a long-term health condition with distinct clinical courses. Its characterization together with the identification of prognostic factors for a persistent LBP course may trigger the development of personalized interventions. This study aimed to investigate the courses of chronic LBP (CLBP), its cumulative impact, and the indicators for the persistence of pain. MATERIAL AND METHODS: Patients with active CLBP from the EpiDoC, a population-based cohort study of a randomly recruited sample of 10.661 adults with prolonged follow-up, were considered. Pain, disability, and health-related quality of life (HRQoL) were assessed at three time-points over five years. According to their pain symptoms over time, participants were classified as having a persistent (pain at the baseline and at all the subsequent time-points) or a relapsing pain course (pain at the baseline and no pain at least in one of the subsequent time-points). A mixed ANOVA was used to compare mean differences within and between patients of distinct courses. Prognostic indicators for the persistent LBP course were modulated through logistic regression. RESULTS: Among the 1.201 adults with active CLBP at baseline, 634 (52.8%) completed the three time-points of data collection: 400 (63.1%) had a persistent and 234 (36.9%) a relapsing course. Statistically significant interactions were found between the group and time on disability (F (2,1258) = 23.779, p<0.001) and HRQoL (F (2,1252) = 82.779, p<0.001). In the adjusted model, the persistent course was associated with the disability level (OR 1.86, CI95% 1.40-2.40, p<0.001), depressive symptoms (OR 1.96, CI95% 1.21-3.18, p = 0.007), female gender (OR 1.90, CI95% 1.26-2.87, p = 0.002) and having a manual job (OR 1.46, CI95% 1.02-2.10, p = 0.040). CONCLUSION: In the long-term, patients with CLBP may follow a persistent or relapsing course of pain. Being female, presenting depressive symptoms, having a manual job and higher disability at baseline predicts a persistent course of LBP.

Prevalence of undiagnosed rheumatic and musculoskeletal diseases and its association with health-related quality of life and with physical function.

AIM: To estimate the disease specific prevalence of undiagnosed rheumatic and musculoskeletal diseases (RMDs) in Portugal and determine if people with undiagnosed RMDs have worse quality of life, physical function and higher health resources consumption, than people without RMDs. METHODS: A subgroup analysis of EpiReumaPt was made that included all participants≥18 years evaluated by a rheumatologist. Participants were stratified into three groups: undiagnosed RMDs; previously diagnosed RMDs; non-RMDs. A descriptive analysis of the three groups was performed. To estimate the prevalence of undiagnosed RMDs, weighted proportion were computed considering the sample design. The three groups were compared (Undiagnosed RMDs vs non-RMDs; Previously diagnosed RMDs vs non-RMDs) for health related quality of life (HRQoL) (EQ5D), physical function (HAQ), mental health (HADS) and health resources consumption. The effect of being undiagnosed for these outcomes was assessed in multivariable models adjusted for age, gender, geographical region and years of education (reference: non-RMD). RESULTS: A total of 3877 participants were included. The prevalence of undiagnosed RMDs was 29%. Compared to participants without RMDs, undiagnosed participants had lower HRQoL (EQ-5D: ß (95% CI)=-0.07 (-0.103,-0.043)) and physical function (HAQ: ß (95% CI)=0.10 (0.05, 0.15)), more anxiety (OR (95% CI)=2.3 (1.4, 3.7)) and depression symptoms (OR (95% CI)=1.4 (0.8, 2.4)). Undiagnosed RMDs participants were more likely to visit an orthopedist (OR (95% CI)=2.0 (1.1, 3.5)) and had a higher number of orthopedic appointments (IRR (95% CI)=2.5 (1.3, 4.9)) than participants without RMDs. CONCLUSION: Patients with undiagnosed RMDs are frequent in Portugal, have worse HRQoL, physical function and mental health than people without RMDs. Undiagnosed patients are nonetheless consumers of health resources and tend to seek help from specialties other than rheumatology. Increasing the awareness of RMDs might promote their early identification and treatment leading to both personal and societal benefits.