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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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Gomes et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., (© 2022 the International Society of Dermatology.)

Arthritis in the paediatric population is the hallmark of many rheumatic inflammatory diseases, as well as other cutaneous, infectious, or neoplastic conditions. It can be quite devastating, whereby prompt recognition and treatment of these disorders are essential. However, arthritis can sometimes be mistaken for other cutaneous or genetic conditions leading to misdiagnosis and overtreatment. Pachydermodactyly is a rare and benign form of digital fibromatosis, usually manifested by swelling of the proximal interphalangeal joints of both hands, mimicking arthritis. The authors report a case of a 12-year-old boy with a one-year history of painless swelling of the proximal interphalangeal joints of both hands that was referred to the Paediatric Rheumatology department due to the suspicion of juvenile idiopathic arthritis. The diagnostic work-up was unremarkable, and the patient remained asymptomatic over an 18-month follow-up period. A diagnosis of pachydermodactyly was assumed and no treatment was introduced, given the benign nature of the disorder and absence of symptoms. Therefore, it was possible to safely discharge the patient from the Paediatric Rheumatology clinic.

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: β (95% CI)=-0.07 (-0.103,-0.043)) and physical function (HAQ: β (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.

Erythema nodosum (EN) is a type of panniculitis often benign and self-limited. It may, however, be associated with numerous causes, the most common being infections (namely streptococcal infections), of which tuberculosis (TB) is also one. We report the case of a 43-year-old woman who was referred to our outpatient department with signs of a recurrent EN along with an asymmetrical oligoarthritis of the lower limbs. The investigation excluded all etiological causes of EN, except the interferon gamma release assay (IGRA) which was positive. It was assumed a latent TB infection was the cause of EN. Treatment with isoniazid was started, besides prednisolone and colchicine, with maintained clinical remission. There are just a few cases published about this subject and this intends to emphasize the importance of medical history and of an exhaustive search for a cause, as it may slip away due to the absence of symptoms., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Lourenço et al.)

Background: Methotrexate (MTX) is an anti-folate drug with anti-proliferative and anti-inflammatory effects. MTX proved to be the most highly effective, fast-acting disease modifying anti-rheumatic drug (DMARD), being widely used for the treatment of rheumatoid arthritis (RA). This review aims to describe the main genetic variants identified concerning proteins that play a role in methotrexate's kinetics and efficiency profile., Methods: A literature review was conducted since January of 2000 until December 2020, by searching the PubMed and Embase bibliographic databases, employing the following MeSH terms: methotrexate, pharmacogenetics, pharmacokinetics, and rheumatoid arthritis. The search was limited to articles in English language. Two independent reviewers screened the titles and abstracts followed by a full-text review to assess papers regarding their eligibility. A total of 48 articles matched the research criteria and were analyzed., Results: Reduced folate carrier 1 (RFC1), a constitutively expressed folate transport protein that has high affinity for MTX is responsible, almost exclusively, for the transport of folate and MTX into the cell. The most studied variant of the gene is the 80G&gt;A variant, mapped within exon 2, on chromosome 21. It seems to improve RA responses to MTX, clinical efficacy with long disease remission. ABC transporters are involved in the efflux of MTX from cells. An increased expression and function of these transporters should decrease MTX concentrations in target cells, resulting in lack of therapeutic response. ABCB1 3435 C/T is a high frequency polymorphism, significantly associated with RA good responses, symptom remission and reduced adverse events, due to MTX treatment. Thymidylate synthase (TYMS) is involved in thymidine synthesis. MTX decreases TYMS activity by inhibition and decreasing the access to tetrahydrofolate (THF) cofactors. The most common genetic variant of the TYMS gene consists of a 28 bp tandem repeat, with double and triple number of repeats (2R and 3R). The 3R allele genotype was associated with decreased efficacy and increased toxicity. The 5,10-methylenetetrahydrofolate reductase (MTHFR) enzyme is indirectly inhibited by MTX. The most common SNPs of the MTHFR gene are C677T and A1298C. Both are associated with a decreased efficacy and an increased toxicity of MTX., Conclusion: MTX response is affected by many gene variants; the effect of each variant separately is likely to be small. Additionally, gene-gene interaction seems to enhance the potential role of linkage disequilibrium. This shows the emerging need for a better gene characterization and to improve the knowledge about variants distribution according to ethnicity, to explain different responses to MTX at an individual level.

Objectives: To estimate the prevalence of medical care-seeking among adults with low back pain (LBP) and to characterise and compare use of diagnostic procedures and medical management between primary and secondary care., Design: Cross-sectional study., Setting: Data from the EpiReumaPt, a nationwide population-based study conducted in Portugal including a representative sample of non-institutionalised adults (n=10 661) stratified by administrative territorial units was analysed., Participants: Individuals who self-reported history of LBP within the previous 12 months (n=6434) and sought medical care for this problem in the same period (n=2618)., Outcome Measures: Patients' self-reported diagnostic workup and management procedures performed by medical care for LBP collected through a structured questionnaire. Medical care procedures were stratified by level of care., Results: The prevalence of medical care-seeking for LBP was 38.0% (95% CI 35.9% to 40.1%). Primary care in isolation (45.3%) was the most sought level of care. Emergency departments (25.9%) and orthopaedics (19.4%) were the most sought secondary medical specialties. Several pathoanatomical diagnoses were used, supported by laboratory or imaging tests (91.1%). Disc herniation (20.4%) and osteoarthritis (19.7%) were the most frequent diagnoses, and X-ray (63.7%) was the most frequent diagnostic procedure self-reported by individuals. Most (75.1%) reported being treated for LBP: 80.4% with oral medication and 49.9% with injectables. The mean duration of pharmacological treatment was 104.24 (SD, 266.80) days. The use of pathoanatomical diagnoses, laboratory or imaging tests, and pharmacological treatments were generally more frequent for secondary care (p<0.05). Approximately one-quarter of individuals (24.5%) reported seeking care from additional healthcare providers, physiotherapists (66.9%) were the most frequent., Conclusions: Medical care for LBP is frequent and associated with high levels of pathoanatomical diagnoses, imaging and laboratory tests and pharmacological therapy in both primary and secondary care settings. Funding and delivery actions should be prioritised to assure appropriate care for LBP., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Platelet-rich plasma injections have been a therapeutic option with exponential growth in several pathologies in the last decades, particularly musculoskeletal for their effect on improving pain and functionality. Rheumatoid arthritis is a chronic joint disease, which involves inflammation of the synovial membrane with cartilage and juxta-articular bone destruction. Conventional and biological disease-modifying anti-rheumatoid drugs are the cornerstone of the treatment of this disease. However, the use of intra-articular glucocorticoids is often necessary and the role of platelet-rich plasma injections in these patients remains uncertain. A literature review was carried out through the PubMed database, Cochrane and Google Scholar for the search terms "rheumatoid arthritis" and "platelet-rich plasma". Eleven studies have been included in this review: two of these are in vitro studies, five are animal studies, one case report, two case series and one randomized controlled trial. Most of the studies demonstrated a decrease in pain and inflammatory mediators and improvement of functional outcomes, with no severe adverse effects reported. However, the quantity and quality of literature about the effects and safety of plasma-rich plasma injections in rheumatoid arthritis patients are still scarce. It is essential that well-designed randomized controlled trials are made on this topic to understand if platelet-rich plasma may be useful as a coadjuvant therapy in rheumatoid arthritis., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Moeda et al.)

Introduction: Hand osteoarthritis (HOA) is a prevalent rheumatic disease that may cause significant disability. The Functional index for HOA (FIHOA) is a validated questionnaire to evaluate loss of function in patients with HOA., Objective: To undertake a cross-cultural adaptation and validation of FIHOA into Portuguese., Patients and Methods: First, the original French version of FIHOA had been forward-backward translated into Portuguese, according to the guidelines for cross-cultural adaptation. Secondly, patients with primary HOA were consecutively recruited in three Portuguese rheumatology outpatient clinics between May 2016 and April 2018. The final consensual Portuguese version of FIHOA was administered to 52 patients. A numerical rating scale (NRS - 0 to 100mm) for hand pain and for perceived hand dysfunction was also registered. Ten randomly selected patients were re-administered the same tools 5 to 15 days later. Internal consistency, test-retest reliability, internal construct validity and external validity related to dysfunction NRS were evaluated., Results: Fifty-two patients were evaluated: all right-handed, 96% women, mean age of 63 (10) years and 8 (6) years of disease duration. Mean (SD) pain and dysfunction were 47 (25) and 46 (25), respectively, with 68% patients being symptomatic. Mean (SD) FIHOA was 7 (5). Cronbach's alpha for internal consistency was high and adequate (0.87) and corrected item-total correlation revealed adequate performance. For reliability, Spearman's rho coefficient was 0.88 and total intraclass correlation coefficient (ICC) between test and retest was 0.87, showing good reliability. Factor analysis revealed three factors accounting for 71% of the variance of the score, with the first one (including questions 1, 2, 3 and 10) being responsible for 47% of the variance. Spearman's rho between FIHOA and dysfunction NRS was 0.5, showing a moderate but significant correlation and moderate external validity., Conclusion: The Portuguese version of FIHOA is a consistent, reliable, and valid instrument to measure loss of function in HOA Portuguese patients.

Background: Multidrug-resistant organisms (MDROs) are a reality that can alter the paradigm of treatment and prevention of infection in patients with liver cirrhosis (LC)., Objective: Identify risk factors for the occurrence of MDROs in patients with LC., Patients and Methods: Prospective study from October 2017 to March 2018 in consecutively hospitalized patients with decompensated LC with infection. Blood, urine and ascitic fluid cultures were analyzed. A p-value ≤0.05 was considered statistically significant., Results: MDROs isolated in 18 of 52 episodes of infection. MDROs were associated with the use of proton pump inhibitors (PPIs) (p=0.0312), antibiotic therapy in the last 90 days (p=0.0033) and discharge within preceding 30 days or current hospitalization above 48h (p=0.0082). There was higher 90-day mortality in patients with MDROs infection (71.4% versus 35.7%, p=0.0316)., Conclusion: MDROs infections were prevalent in this cohort and associated with 90-day mortality. Use of PPIs and antibiotics increased the risk of MDROs infections, suggesting that its prescription should be restricted to formal indication. Hospitalization was associated with the onset of MDROs, so LC patients should stay at the hospital the least possible. It is relevant to investigate other factors predisposing to the emergence of these microorganisms, in order to prevent it., (Copyright © 2021 Elsevier España, S.L.U. All rights reserved.)

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.

Cat scratch disease (CSD) is a zoonosis caused by Bartonella henselae, which is usually transmitted to humans through scratches or bites from infected cats. It is primarily a disease of children and adolescents, although it can affect individuals of any age. In approximately 10% of cases, patients can present atypical manifestations that may involve the musculoskeletal system. Herein, we report a case of a healthy 51-year-old man that developed low-grade fever and regional lymphadenopathy, followed by erythema nodosum and oligoarthritis. He had been scratched and bitten by his cat before the onset of symptoms. The diagnosis was confirmed serologically by the presence of high titers of specific IgG antibodies. Bartonella henselae was also detected in the blood of the owner's cat by PCR and DNA sequencing.

Background: Axial Spondyloarthritis (axSpA) is a chronic, inflammatory rheumatic disease that affects the axial skeleton, causing pain, stiffness, and fatigue. Genetics and environmental factors such as microbiota and microtrauma are known causes of disease susceptibility and progression. Murine models of axSpA found a decisive role for biomechanical stress as an inducer of enthesitis and new bone formation. Here, we hypothesize that muscle properties in axSpA patients are compromised and influenced by genetic background., Objectives: To improve our current knowledge of axSpA physiopathology, we aim to characterize axial and peripheral muscle properties and identify genetic and protein biomarker that might explain such properties., Methods: A cross-sectional study will be conducted on 48 participants aged 18-50 years old, involving patients with axSpA (according to ASAS classification criteria, symptoms duration < 10 years) and healthy controls matched by gender, age, and levels of physical activity. We will collect epidemiological and clinical data and perform a detailed, whole body and segmental, myofascial characterization (focusing on multifidus, brachioradialis and the gastrocnemius lateralis) concerning: a) Physical Properties (stiffness, tone and elasticity), assessed by MyotonPRO®; b) Strength, by a dynamometer; c) Mass, by bioimpedance; d) Performance through gait speed and 60-second sit-to-stand test; e) Histological and cellular/ molecular characterization through ultrasound-guided biopsies of multifidus muscle; f) Magnetic Resonance Imaging (MRI) characterization of paravertebral muscles. Furthermore, we will perform an integrated transcriptomics and proteomics analysis of peripheral blood samples., Discussion: The innovative and multidisciplinary approaches of this project rely on the elucidation of myofascial physical properties in axSpA and also on the establishment of a biological signature that relates to specific muscle properties. This hitherto unstudied link between gene/protein signatures and muscle properties may enhance our understanding of axSpA physiopathology and reveal new and useful diagnostic and therapeutic targets.

CD4 + T cells mediate rheumatoid arthritis (RA) pathogenesis through both antibody-dependent and independent mechanisms. It remains unclear how synovial microenvironment impinges on CD4 + T cells pathogenic functions. Here, we identified a TLR4 + follicular helper T (Tfh) cell-like population present in the blood and expanded in synovial fluid. TLR4 + T cells possess a two-pronged pathogenic activity whereby direct TLR4 + engagement by endogenous ligands in the arthritic joint reprograms them from an IL-21 response, known to sponsor antibody production towards an IL-17 inflammatory program recognized to fuel tissue damage. Ex vivo, synovial fluid TLR4 + T cells produced IL-17, but not IL-21. Blocking TLR4 signaling with a specific inhibitor impaired IL-17 production in response to synovial fluid recognition. Mechanistically, we unveiled that T-cell HLA-DR regulates their TLR4 expression. TLR4 + T cells appear to uniquely reconcile an ability to promote systemic antibody production with a local synovial driven tissue damage program., (© 2021. The Author(s).)

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., (©Luís Antunes Gomes, Maria João Gregório, Tatiana A Iakovleva, Rute Dinis de Sousa, John Bessant, Pedro Oliveira, Jaime C Branco, Helena Canhão, Ana Maria Rodrigues. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 31.08.2021.)

Background: Spondyloarthritis (SpA) are the most common group of chronic inflammatory rheumatic diseases affecting about 1.5% of the adult Caucasian population. Low back pain is the most common symptom. The aetiopathogenesis of SpA is multifactorial, with well-known genetic and environmental contributions. Furthermore, muscle properties might also be involved in the pathophysiological process and these could be modulated by the genetic background. Alpha-actinin-3 ( ACTN3 ) and Vitamin D receptor ( VDR ) genes are well-known genes related with muscle performance. Our aim was to analyze four SNPs of these genes and to evaluate their influence in axial SpA (axSpA) susceptibility, phenotype and muscle properties., Methods: We performed a pilot study based on case-control approach involving 56 participants: 28 axSpA patients and 28 healthy controls matched by age, gender and levels of physical activity. Clinical, epidemiological and muscle characterization data-muscle physical properties (stiffness, tone, and elasticity), strength, mass, and performance, were collected. Two different muscles were considered for analysis, the Multifidus and Gastrocnemius. Four SNPs of ACTN3 (rs1815739) and VDR (rs2228570, rs731236, and rs7975232), were selected, analyzed and correlated with clinical, epidemiological and muscle characterization data., Results: In total, 51 individuals (27 axSpA patients and 24 matched controls) were eligible for further genetic analysis, 66.7% being male and with a mean age of 36 years. Muscle physical properties, muscle strength and muscle mass were similar in both groups; however, axSpA patients showed a decrease in muscle performance. None of the studied SNPs were associated with disease susceptibility/phenotype, muscle physical properties, muscle strength or muscle mass. However, ACTN3 rs1815739 and VDR rs2228570 were shown to be associated with muscle performance., Conclusion: Our results suggest an association between ACTN3 and VDR polymorphisms and muscle performance in axSpA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Pimenta, Mateus, Rodrigues-Manica, Pinheiro-Torres, Neto, Domingues, Lage Crespo, Sardoo, Machado, Branco, Silva and Pimentel-Santos.)

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 (β 4.6 CI 0.7;8.5) and diabetes (β 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.

Objective: Biobanks for research (BBR) have enormous value for research, including those specifically oriented to chronic diseases. Knowing public attitudes and perceptions is key to design and implement patient-centered BBR. We assessed patient awareness, perception and choices among rheumatology outpatients regarding aging biobanking activities., Methods: We conducted a cross-sectional survey of patients, aged 50 or older, attending an outpatient rheumatology tertiary department. Demographic data and perceptions about biobanking were collected and statistical analysis was performed., Results: 132 valid questionnaires were obtained (mean age: 63,4; 68,2% female; mean education years: 8,35). 61,7% of respondents did not know the specific term "biobank", 57,7% knew they could donate biological material for BBR, 89,9% agreed with these infrastructures and 88,3% would consider participation Those participants with more years of education were more knowledgeable and prone to biobank participation. Willingness to participate in BBR was mainly related (86,4%) to the advancement of scientific knowledge and not individual gain. Scientific research institutes were indicated as the most adequate institutions to manage BBR. Informed consent, anonymity and confidentiality ranked as top requisites for biobank participation. 61,3% of respondents expressed their agreement with aging biobanks, considering these as a sign of respect for specific problems of people of older ages such as higher disease burdens., Conclusion: Knowledge of biobanks was found to be limited. Participants were positive toward the setting up of biobanks in general and patient-centered aging biobanks in particular. Knowledge about biobanks and acceptance were higher among participants with higher education years.

Background: In response to rapid global spread of the newly emerged coronavirus disease 2019 (COVID-19), universities transitioned to online learning and telework to decrease risks of inter-person contact. To help administrators respond to the COVID-19 pandemic and better understand its impacts, we surveyed SARS-CoV-2 seroprevalence among NOVA University employees and assessed community mental health. Methods: Data were collected from voluntary participants at six NOVA University locations, in the Lisbon metropolitan area, from June 15-30, 2020. All subjects provided written informed consent. Of 1,627 recruited participants (mean age 42.0 ± 12.3 years), 1,624 were tested. Prior to blood collection, participants completed a questionnaire that assessed: COVID-19 symptoms during the previous 14 days, chronic non-communicable diseases, chronic medication, anxiety, and depression symptoms. SARS-CoV-2 serology tests were then performed, and results communicated approximately 4 days after blood draw. Participants with positive serology tests were contacted to assess COVID-19 symptoms since February. Results: Estimated prevalence of SARS-CoV-2 IgG antibodies was 3.1% ( n = 50), of which 43.5% reported symptoms in the previous 4 months. The Medical School had the highest seroprevalence (6.2%). Participants reported having at least one chronic disease (63.7%), depression-like symptoms (2.1%), and anxiety symptoms (8.1%). Rates of depression and anxiety symptoms were significantly higher in women, with sleep hours and occasional alcohol consumption negatively associated with depression. Male gender, older age, and sleep hours negatively associated with anxiety symptoms. School of employment and presence of comorbidities positively associated with anxiety. Conclusion: By measuring seroprevalence of SARS-CoV-2 antibodies among NOVA employees and assessing subjects' mental health, we aim to help administrators at European public universities in urban areas, such as Lisbon, Portugal, better understand the needs of their communities. This study resulted in implementation of a stricter contingency plan in the Medical School, while other schools continued to follow Government mitigation guidelines. These findings may also guide the development of tailored strategies to ensure physical and mental health of the academic community during this pandemic crisis. We conclude that, together with COVID-19 contingency plans, psychological support services and facilities to help people effectively face pandemic-associated challenges and minimise anxiety and depression should be implemented., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lopes, Henriques, Santos-Dias, Nunes-da-Silva, Gonçalves, de Sousa, Abdulghani, Eletério, Braga, Soares, Branco, Canhão and Rodrigues.)

Objective: The human resting myofascial tone maintains the body tone in a neutral posture, the assessment of this and other muscle physical properties (MPP) is relevant, since, it is altered in many pathological states., Patients and Methods: Seventeen healthy subjects (8 males), between 18-50 years old, were assessed. The MPP of lower lumbar muscles was evaluated on right and left sides during prone resting position using two devices; myotonometry (stiffness, elasticity and tone) and ultrasound-based shear-wave elastography (SWE) (shear modulus). MTM measurements were performed at two anatomic points (ANp), selected by an experienced reader and at an adjacent ultra-sound determined point (USp). Myotonometry measurements of the erector spinae and SWE measurements of multifidus muscles at the L3-4 level were compared between genders and sides. The intra-reader reliability (IRR) for each device and correlations between techniques were analysed. MTM measurements performed at ANp and USp were compared. The intraclass correlation coefficient (ICC) was assessed for both devices. Correlations between stiffness (myotonometry) and shear modulus (SWE) at the respective muscle depths were assessed with Spearman correlation., Results: Males had greater stiffness and tone than females, particularly on the dominant side. MPP assessed by myotonometry were not different between ANp and USp. Good/Excellent IRR was documented for measurements by MTM (ICC≥0.90) and SWE (ICC≥0.85). No correlation in myotonometry stiffness and SWE shear modulus was found. For myotonometry assessments, the addition of ultrasonography was not different from anatomic localizations. No correlation of measurements was found between devices assessing respective L3-4 level muscles., Conclusions: Gender and side differences must be considered when assessing MPP in axial muscles. For MTM assessments, the addition of ultrasonography was not different to anatomic references. No correlation was found between devices.

Objectives: The purpose of this study is to assess the independent effects of depression and excess body weight (EBW) on cognition and functioning in a community sample of young adults., Methods: This was a cross-sectional of 943 young adults. The diagnosis of a current depressive episode was performed using the Mini International Neuropsychiatric Interview (MINI). Cognition and functioning were assessed using the Montreal Cognitive Assessment (MoCA) and the Functional Assessment Short Test (FAST), respectively. The EBW was defined as BMI ≥ 25.0 kg/m 2 . The independent main effects of depression and EBW, as well as the analysis interaction were performed using two-way analysis of covariance (ANCOVA)., Results: The total sample comprised 943 adults, with 75 (8.0%) individuals diagnosed with a current depressive episode and 493 (52,6%) with EBW. Of the 75 subjects with depression, 40 were identified with EBW comorbidity. Subjects with depression and EBW comorbidity reported greater cognitive and functional impairment, as compared to individuals with depression without EBW. There was a significant interaction between depression and EBW on MoCA total (p<0.001) as well as FAST total (p=0.010), work (p=0.002), cognition (p=0.023), finances (p=0.032) and relationships domains (p=0.008)., Conclusions: The adverse effects of depression and EBW are independent and cumulative with respect to cognition and functioning of individuals. The understanding of the complex interactions between cognition, functioning, EBW and depression are important for development of preventive and therapeutic strategies., (Copyright © 2020. Published by Elsevier B.V.)

Seroprevalence studies are crucial both for estimating the prevalence of SARS-CoV-2 exposure and to provide a measure for the efficiency of the confinement measures. Portuguese universities were closed on March 16th 2020, when Portugal only registered 62 SARS-CoV-2 infection cases per million. We have validated a SARS-CoV-2 ELISA assay to a stabilized full-length spike protein using 216 pre-pandemic and 19 molecularly diagnosed SARS-CoV-2 positive individual's samples. At NOVA University of Lisbon, presential work was partially resumed on May 25th with staggered schedules. From June 15th to 30th, 3-4 weeks after the easing of confinement measures, we screened 1,636 collaborators of NOVA university of Lisbon for the presence of SARS-CoV-2 spike specific IgA and IgG antibodies. We found that spike-specific IgG in 50 of 1,636 participants (3.0%), none of which had anti-spike IgA antibodies. As participants self-reported as asymptomatic or paucisymptomatic, our study also provides a measurement of the prevalence of asymptomatic/paucisymptomatic SARS-CoV-2 infections. Our study suggests that essential workers have a 2-fold increase in viral exposure, when compared to non-essential workers that observed confinement. Additional serological surveys in different population subgroups will paint a broader picture of the effect of the confinement measures in the broader community., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Gonçalves, Sousa, Jacinto, Silva, Paula, Sousa, Zahedi, Carvalho, Cabral, Costa, Branco, Canhão, Alves, Rodrigues and Soares.)

Background: Studies on the field of mood disorders has mainly focusing on the risk factors associated to develop the illness or the clinical factors associated with the clinical progression. Less attention was given to factors such as resilience that may be associated with better outcomes in the course of mood disorders. In this study, we assessed the mediation effect of resilience on the relationship between childhood trauma and mood disorders, as well as the severity of depressive symptoms in a population-based sample., Methods: This is a cross-sectional study with a community sample of young adults with bipolar disorder (BD), major depressive disorder (MDD), and community controls without any mood disorder. The trauma experiences during childhood were assessed by Childhood Trauma Questionnaire (CTQ). The severity of depressive symptoms was assessed using the Montgomery-Asberg Depression Rating Scale (MADRS) and to assess the resilience was used the Resilience Scale (RS-25)., Results: All subtypes of trauma were associated with both MDD and BD, however, only physical and emotional abuse differentiated BD from MDD subjects. Bootstrapping-enhanced mediation analyses indicated that resilience partly mediated the association of childhood trauma to both mood disorder and severity of depression., Limitation: The employed mediation analyses are cross-sectional in nature, which limits any firm conclusions regarding causality., Conclusions: The findings support the clinical assumption that resilient subjects may be partly protected against the detrimental long-term effects of childhood trauma. This study provides important information regarding the relationships among childhood trauma, resilience, and mood disorder., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020. Published by Elsevier B.V.)

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.

A 14-Item Mediterranean Diet Adherence Screener (MEDAS) questionnaire was developed and validated in face-to-face interviews, but not via telephone. The aims of this study were to evaluate the validity and reliability of a telephone-administered version of the MEDAS as well as to validate the Portuguese version of the MEDAS questionnaire. A convenience community-based sample of adults ( n = 224) participated in a three-stage survey. First, trained researchers administered MEDAS via a telephone. Second, the Portuguese version of Food Frequency Questionnaire (FFQ), and MEDAS were administered in a semi-structured face-to-face interview. Finally, MEDAS was again administered via telephone. The telephone-administered MEDAS questionnaire was compared with the face-to-face-version using several metrics. The telephone-administered MEDAS was significantly correlated with the face-to-face-administered MEDAS [r = 0.805, p < 0.001; interclass correlation coefficient (ICC) = 0.803, p < 0.001] and showed strong agreement (k = 0.60). The MEDAS scores that were obtained in the first and second telephone interviews were significantly correlated (r = 0.661, p < 0.001; ICC = 0.639, p < 0.001). The overall agreement between the Portuguese version of MEDAS and the FFQ-derived Mediterranean diet adherence score had a Cohen's k = 0.39. The telephone-administered version of MEDAS is a valid tool for assessing the adherence to the Mediterranean diet and acquiring data for large population-based studies.

Background: The vasculitides are a group of rare diseases with different manifestations and outcomes. New therapeutic options have led to the need for long-term registries. The Rheumatic Diseases Portuguese Register, Reuma.pt, is a web-based electronic clinical record, created in 2008, which currently includes specific modules for 12 diseases and > 20,000 patients registered from 79 rheumatology centres. On October 2014, a dedicated module for vasculitis was created as part of the European Vasculitis Society collaborative network, enabling prospective collection and central storage of encrypted data from patients with this condition. All Portuguese rheumatology centres were invited to participate. Data regarding demographics, diagnosis, classification criteria, assessment tools, and treatment were collected. We aim to describe the structure of Reuma.pt/vasculitis and characterize the patients registered since its development., Results: A total of 687 patients, with 1945 visits, from 13 centres were registered; mean age was 53.4 ± 19.3 years at last visit and 68.7% were females. The most common diagnoses were Behçet's disease (BD) (42.5%) and giant cell arteritis (GCA) (17.8%). Patients with BD met the International Study Group criteria and the International Criteria for BD in 85.3 and 97.2% of cases, respectively. Within the most common small- and medium-vessel vasculitides registered, median [interquartile range] Birmingham Vasculitis Activity Score (BVAS) at first visit was highest in patients with ANCA-associated vasculitis (AAV) (17.0 [12.0]); there were no differences in the proportion of patients with AAV or polyarteritis nodosa who relapsed (BVAS≥1) or had a major relapse (≥1 major BVAS item) during prospective assessment (p = 1.00, p = 0.479). Biologic treatment was prescribed in 0.8% of patients with GCA, 26.7% of patients with AAV, and 7.6% of patients with BD. There were 34 (4.9%) deaths reported., Conclusions: Reuma.pt/vasculitis is a bespoke web-based registry adapted for routine care of patients with this form of rare and complex diseases, allowing an efficient data-repository at a national level with the potential to link with other international databases. It facilitates research, trials recruitment, service planning and benchmarking.

Introduction: Nutrition has been underrepresented in the curriculum of many medical schools and therefore physicians do not feel adequately prepared to provide dietary counselling. The aim of the present study is to determine the impact of a Nutrition and Metabolism curricular unit on nutrition attitudes, knowledge and confidence on future clinical practice of medical students., Material and Methods: All the students enrolled in the curricular unit (2017/2018) were invited to complete a questionnaire assessing their nutritional knowledge and eating habits at the beginning and at the end of the semester (n = 310)., Results: Initially, students reported good eating habits and nutrition knowledge. These aspects improved at the end of the study. Moreover, students reported that they felt more confident to do dietary counselling after intervention., Discussion: Most medical students answered affirmatively to all questions related with good habits or eating behaviours, and the acquisition of knowledge had an impact in specific attitudes. After the Nutrition and Metabolism classes the students felt able to provide dietary counselling in different clinical settings, but none of the students felt extremely confident about their competencies for dietary counselling. This can be due to the fact that the students involved were in the first year of the integrated master's degree in medicine, which is a preclinical year, and thus distant from the medical reality and from contact with patients., Conclusion: Nutrition education can have a positive impact on attitudes and eating behaviours, knowledge and in the perception of competencies for dietary counselling.

Background: Non-specific low back pain (NSLBP) is the most prevalent musculoskeletal condition in western countries and is associated with persistent disability and high consumption of health care resources. NSLBP patients first seek primary health care services but the outcomes are often uncertain. This study aimed to examine the clinical course of the outcomes and to identify prognostic indicators for poor outcomes in NSLBP patients who consulted primary care., Methods: A prospective cohort study of 115 patients seeking treatment for NSLBP in primary care was conducted. Participants were consecutively recruited by their General Practitioners (GPs) and then assessed at baseline and 2 and 6 months later. Baseline assessment included socio-demographic and clinical data, psychosocial factors, pain, disability, and health related quality of life (HRQoL). Pain, disability, HRQoL and global perception of change were also assessed at 2 and 6-months' follow-up. In addition, information regarding the GP' practice was collected. Poor outcomes were determined according to the cut-off point used to define a persistent disabling condition and the minimal important change established for disability, pain and for global perception of change. The relationship between variables on baseline and poor outcomes was modulated through binary logistic regression analysis. The significance of associations was evaluated at ≤ 0.05 p-value with 95% confidence intervals (CI) and adjusted odds ratios (AOR)., Results: 110 (94.8%) and 104 (89.7%) participants completed the follow-up assessment at 2 and 6 months, respectively. The mean age (±SD) was 48.06 ± 11.41, with 53.9%, (N = 62) reporting an acute presentation of NSLBP. Six months after GP consultation, 53.8% (N = 56) of the participants reported a persistent disabling condition. An "LBP episode of less than 12 weeks" [AOR: 0.26; 95% CI (0.10, 0.65); AOR: 0.34; 95% CI (0.14, 0.81); AOR: 0.21; 95% CI (0.09, 0.53)],"maladaptive psychosocial factors" [AOR: 2.06; 95% CI (1.40, 3.04); AOR: 1.82; 95% CI (1.27, 2.59); AOR: 1.72; 95% CI (1.20, 2.47)] were significantly associated with poor outcomes on disability, pain and global perception of change, respectively. Besides these factors, being employed reduces the chances of poor outcomes on disability [AOR 0.31; 95% CI (0.11, 0.92)]., Conclusions: A large proportion of LBP patients seeking primary health care reported poor outcomes 6 months after GP consultation. Patients who report chronic LBP, maladaptive psychosocial factors and are unemployed have a significant increase in the risk of poor outcome. These findings suggest the need of implementing effective models of care able to provide early screening and appropriate treatment to those at greatest risk of a poor outcome., Trial Registration: Current Controlled Trials NCT04046874 (August 6, 2019). Retrospectively registered., Competing Interests: The authors have declared that no competing interests exist.

Vitamin D deficiency is prevalent worldwide, but its prevalence is unknown in adult Portuguese population. In Portugal, 66% of adults present Vitamin D insufficiency/deficiency. Winter, living in Azores, older age, and obesity were the most important risk factors. It highlights the need of strategies to prevent vitamin D deficiency in Portugal., Objective: To estimate the prevalence and risk factors of vitamin D deficiency in the adult Portuguese population., Methods: Adults (≥ 18 years old) from the EpiReumaPt Study (2011-2013) were included. Standardized questionnaires on socio-demographic and lifestyle features were obtained. Serum 25-hydroxyvitamin D [25(OH)D] concentrations were evaluated using ADVIA Centaur VitD competitive immunoassay (Siemens Healthineers) in 2015-2017 as 25 (OH)D Level 0: ≤ 10 ng/mL; Level 1: 11-19 ng/mL; Level 2: 20-29 ng/mL, and Level 3: ≥ 30 ng/mL. Weighted multinomial regression analysis was conducted to evaluate the association between socio-demographic and lifestyle variables and vitamin D status., Results: Based on weighted analysis, the estimated prevalence of levels of 25(OH)D ≤ 10, < 20, and < 30 ng/mL was 21.2, 66.6, and 96.4%, respectively. The strongest independent predictors of serum 25 (OH)D ≤ 10 ng/mL were living in the Azores archipelagos (OR 9.39; 95%CI 1.27-69.6) and having the blood sample collection in winter (OR 18.53; 95%CI 7.83-43.87) or spring (11.55; 95%CI 5.18-25.74). Other significant predictors included older age (OR 5.65, 95%CI 2.08-15.35), obesity (OR 2.61; 95%CI 1.35-5.08), current smoking (OR 2.33; 95%CI 1.23-4.43), and female gender (OR 1.9, 95%CI 1.1-3.28). Conversely, physical exercise (OR 0.48, 95%CI 0.28-0.81) and occasional alcohol intake (OR 0.48, 95%CI 0.29-0.81) were associated with a lower risk of 25(OH)D ≤ 10 ng/mL., Conclusion: Vitamin D deficiency/insufficiency [25(OH)D < 20 ng/ml] is highly prevalent in Portugal, affecting > 60% of all Portuguese adults, with strong geographical and seasonal variation. This study highlights the need to critically assess the relevance of vitamin D deficiency as a public health problem and the urgent need for a wide and scientifically robust debate about the most appropriate interventions at the individual and societal levels.

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., Competing Interests: Competing interests: AS received speaker fees from Novartis. FPS received speaker/consultancy/research fees from AbbVie, Novartis, MSD, Eli Lilly, Janssen-Cilag, Pfizer, Biogen, Vitória, Roche, Menarini, AlfaSigma, UCB and Medac. HS received speaker/consultancy fees from AbbVie, Eli Lilly, Janssen-Cilag, Novartis and Pfizer. JTC received speaker/consultancy fees from AbbVie, Amgen, Eli Lilly, Janssen-Cilag, MSD, Novartis, Pfizer and UCB. MB received consultancy fees from AbbVie, Amgen, Eli Lilly, Novartis, Pfizer, Janssen-Cilag, Glaxosmithkline, Biogen. Speaker fee: Janssen-Cilag. SR received speaker/consultancy fees from AbbVie, Eli Lilly, MSD, Novartis, Pfizer and Sanofi., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The aim of this study was to compare the effectiveness of a combined intervention of manual therapy and exercise (MET) versus usual care (UC), on disability, pain intensity and global perceived recovery, in patients with non-specific chronic neck pain (CNP)., Design: Randomized controlled trial., Setting: Outpatient care units., Subjects: Sixty-four non-specific CNP patients were randomly allocated to MET ( n = 32) or UC ( n = 32) groups., Interventions: Participants in the MET group received 12 sessions of mobilization and exercise, whereas the UC group received 15 sessions of usual care in physiotherapy., Main Measures: The primary outcome was disability (Neck Disability Index). The secondary outcomes were pain intensity (Numeric Pain Rating Scale) and global perceived recovery (Patient Global Impression Change). Patients were assessed at baseline, three weeks, six weeks (end of treatment) and at a three-month follow-up., Results: Fifty-eight participants completed the study. No significant between-group difference was observed on disability and pain intensity at baseline. A significant between-group difference was observed on disability at three-week, six-week and three-month follow-up (median (P 25 -P 75 ): 6 (3.25-9.81) vs. 15.5 (11.28-20.75); P < 0.001), favouring the MET group. Regarding pain intensity, a significant between-group difference was observed at six-week and three-month follow-up (median (P 25 -P 75 ): 2 (1-2.51) vs. 5 (3.33-6); P < 0.001), with superiority of effect in MET group. Concerning the global perceived recovery, a significant between-group difference was observed only at the three-month follow-up ( P = 0.001), favouring the MET group., Conclusion: This study's findings suggest that a combination of manual therapy and exercise is more effective than usual care on disability, pain intensity and global perceived recovery.

Benign transient hyperphosphatasemia of infancy and early childhood is a self-limiting condition characterized by transiently increased serum alkaline phosphatase in the absence of liver, kidney or metabolic bone diseases. It is often accidentally found in children under five years old and it might be associated with a variety of underlying clinical disorders. Its pathophysiology remains unclear. Herein, we report a case of a 4-year-old girl with a 1-year history of persistent oligoarticular Juvenile Idiopathic Arthritis, who was found to have transient hyperphosphatasemia during a periodic check-up. This clinical case underlines the importance of promptly recognizing this benign condition, which avoids unnecessary extensive investigations.

Introduction: Psoriatic arthritis (PsA) and ankylosing spondylitis (AS) are chronic disorders that significantly impact patients' quality of life (QoL), health care systems and society. There is very little data on the epidemiology and the impact of PsA and AS in Portugal, so in this study we aim to: 1) estimate the prevalence of PsA and AS in the adult Portuguese population; 2) compare health-related quality of life (QoL) of PsA and AS with the one of other rheumatic and musculoskeletal diseases (RMD) and with subjects with no rheumatic diseases; 3) compare early retirement and productivity loss among PsA and AS with other RMD., Methods: We used data from EpiReumaPt, a population-based survey, conducted from 2011 to 2013, in which 10661 subjects over 18 years old were screened for RMD. Spondyloarthritis (SpA) was defined by a positive expert opinion combined with the fulfillment of the assessment of spondyloarthritis international society (ASAS) criteria for axial and peripheral SpA. Estimates were computed as weighted proportions considering the study design. Logistic regressions were used to compare AS/PsA subjects with other RMD and the adult Portuguese population without rheumatic diseases., Results: Prevalence rate of SpA was 1.6% (95% CI 1.2% to 2.1%). Subjects with AS or PsA had worse QoL, reflected by EQ5D score when compared with the adult Portuguese population without rheumatic diseases (β=- 0.08; p=0.031). AS and PsA also had worst QoL when compared with participants with other RMD (β=-0.22; p>0.001). AS and in comparison to patients with other RMD, PsA subjects retired early due to their illness (OR=4.95; 95% CI 1.54% to 15.93%). A significant proportion of patients with SpA (13.6%) referred absenteeism in the previous 12 months to the interview., Conclusions: AS and PsA were found to be associated with poor QoL and a high rate of disease-related early retirement, emphasizing the burden of such rheumatic conditions in Portugal.

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.

Objectives: To know the effectiveness and safety of non-supervised breathing exercise regimen by promoting patients' self-management, and to investigate if non-supervised breathing exercise regimen shows similar benefits to supervised regimen in improving pain and fibromyalgia (FM) impact on daily life., Material and Methods: Fifty-one women with FM were assigned to: supervised breathing exercise regimen group, non-supervised breathing exercise regimen group, and control group. Pain thresholds tolerance on tender points and FM impact on daily life were evaluated., Results: After 12-weeks of breathing exercises statistical differences were not found between supervised and non-supervised regimen. However, supervised regimen showed additional improvements in pain thresholds tolerance and in pain-FIQ subscale., Conclusion: Our results suggest that performing a non-supervised breathing exercise program could be as safe and effective as the supervised regimen. However, it was observed that there could be a tendency of supervised exercise regimen to show additional benefits in terms of pain., (Copyright © 2019. Published by Elsevier Ltd.)

Background and Aims: Vitamin D deficiency is more common in inflammatory bowel disease (IBD) patients than in the general population. However, there are conflicting data about predictive factors of vitamin D deficiency and its potential association with disease activity. The aims of this study were to determine the prevalence and predictive factors of vitamin D deficiency and to evaluate a possible association with disease activity., Methods: A prospective observational study was conducted, including patients with IBD from January to July 2016. The Endocrine Society guidelines were considered for defining levels of serum 25-hydroxyvitamin D (25-OH-D) as follows: deficient (< 20 ng/mL, < 10 ng/mL being severe deficiency), insufficient (21-29 ng/mL), and adequate (> 30 ng/mL)., Results: A total of 152 patients (52% men; 47.2 ± 17.3 years) were included, of whom 70% had Crohn's disease (CD). Thirty-seven percent of patients were on immunosuppressors and 17% were on biologics. The majority were outpatients (88.2%). Mean 25-OH-D levels were 17.1 ± 8 ng/mL (CD: 16.7 ± 8 ng/mL vs. ulcerative colitis: 17.6 ± 7 ng/mL, p = 0.1). Inadequate levels were present in 90.8% of patients (deficiency: 68.4%; insufficiency: 22.4%). A significant negative correlation between 25-OH-D levels and age ( r = -0.2, p = 0.04), C-reactive protein (CRP) levels ( r = -0.22, p = 0.004), and Harvey-Bradshaw index (HBi) ( r = -0.32, p = 0.001) was found. Patients with severe deficiency showed a higher CRP (0.6 vs. 1.4 mg/dL, p = 0.03), erythrocyte sedimentation rate (ESR) (22 vs. 31 mm/h, p = 0.03), and HBi (2 vs. 5, p < 0.001) and lower hemoglobin (13.6 vs. 12.7 g/dL, p = 0.02). There was no association between vitamin D deficiency and gender, type, extent, and duration of disease, surgery, and other measures of disease activity, such as ESR, hemoglobin (these 2 items except for severe deficiency), fecal calprotectin, or Truelove and Witts classification., Conclusions: There is a high prevalence of inadequate levels of vitamin D in IBD patients, particularly deficiency (68.4%). There seems to exist an association between lower levels of vitamin D and higher disease activity, especially in CD.

Background: Osteoporotic fractures are a major cause of morbidity and mortality. It is recognized that persistence with medication is crucial to reach optimal clinical outcomes. We aimed to estimate the persistence level to weekly and monthly oral bisphosphonates (OBP) in women with postmenopausal osteoporosis (PMO) over 24 months from therapy initiation in a population-based setting., Methods: Prospective observational cohort study of PMO women ≥50 years initiating OBP recruited through community pharmacies. Data were collected at baseline during face-to-face interviews. Follow-up included pharmacy records (refill dates and medication possession; cohort 1) and telephone-surveys for patients who agreed to be interviewed (cohort 2). Patients were classified as persistent if they refilled their prescription within 30 days after exhausting the time covered by their previous supply. Log-rank tests were used to compare Kaplan-Meier curves of time to non-persistence., Results: Of 427 women recruited with a mean age of 65.0 years, 380 (89%) agreed to be interviewed (cohort 2). Over 24-months of follow-up, 3.4% (95% CI: [2.0%; 5.6%]) of all subjects were persistent to OBP based on pharmacy records. Analysis combining both self-reported information and pharmacy records (cohort 2) showed a persistence estimate of 20.0% (95% CI: [16.1%; 24.2%]). Lower persistence was associated with more frequent OBP dosing and living alone. The most common reason for treatment discontinuation was self-reported adverse events (27.6%)., Conclusions: Results indicate a low level of persistence with OBP. Barriers and reasons leading to discontinuation of anti-PMO therapies should be proactively addressed to promote persistence and improve fracture protection.

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.

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.

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.

Aims: Clinical risk factors and bone mineral densitometry underestimate low-energy fracture (LEF) risk in people with diabetes. We aim to estimate the prevalence of LEF in diabetics, compare with nondiabetics; and evaluate possible predictors of LEF in people with diabetes., Methods: Cross-sectional, population-based study in Portuguese subjects over 40 years-old. Estimates computed as weighted proportions/means, considering sample design. Multivariate logistic regression models to evaluate the association of diabetes and LEF; and predictors of LEF in diabetics., Results: 7675 subjects were analysed, of which 1173 reported diabetes. Diabetics were older (mean age 66.0 ± 11.49y), more frequently reported osteoporosis and falls in the previous 12 months (32.4% vs. 22.9%). Prevalence of self-reported LEF was 16.2% (95% CI:13.68-19.13) among diabetics (vs. 13.3%, 95% CI:12.14-14.57, in nondiabetics); OR for the association diabetes and LEF:1.26, 95% CI:1.01-1.58, p = 0.045 (in women, adjusted OR:1.41, 95% CI:1.05-1.89, p = 0.02). Thirty percent of diabetics reported at least one major LEF and 70% in other sites. In diabetics, LEF was independently associated with self-reported osteoporosis and falls in the previous 12 months., Conclusion: People with diabetes reported more falls and had higher prevalence of self-reported LEF. Self-reported osteoporosis and falls were associated with LEF in diabetics. Our findings emphasize the need for fracture and falls preventive measures in diabetics., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: Neck pain is a common musculoskeletal disorder worldwide. It can result in significant disability and impaired quality of life. More than 50% of patients with neck pain still report symptoms 1 year later despite receiving different forms of non-pharmacological and pharmacological treatment. Identifying patient characteristics that are modifiable or predict recovery and non-recovery for an individual patient might identify ways of improving outcomes. This systematic review aims to comprehensively summarise the existing evidence regarding baseline patient characteristics associated with recovery and non-recovery, as defined by measures of pain intensity, disability and global perceived improvement., Methods and Analysis: Six electronic databases, PubMed, CINAHL, PEDro Database, EMBASE, Cochrane Library and Web of Science, will be searched, with terms related to the review question such as neck pain, prognostic or predictive research, from inception to 28 September of 2018. Studies will be included if they have investigated an association between patient characteristics and outcomes, with at least one follow-up time point. Two independent reviewers will screen the titles and abstracts followed by a full-text review to assess papers regarding their eligibility. Data from included papers will be extracted using standardised forms, including study and participants' characteristics, outcomes, prognostic factors and effect size of the association. The risk of bias of each study will be assessed using the Quality in Prognostic Studies tool. A narrative synthesis will be conducted considering the strength, consistency of results and the methodological quality., Ethics and Dissemination: This systematic review does not require ethical approval. The results will be disseminated through publication in a peer-review journal, as a chapter of a doctoral thesis and through presentations at national and international conferences., Prospero Registration Number: CRD42018091183., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)