Assessing Physical Activity and Sleep in Axial Spondyloarthritis: Measuring the Gap.

Patients with axial spondyloarthritis (axSpA) frequently report pain, stiffness, fatigue, and sleep problems, which may lead to impaired physical activity. The majority of reported-on measures evaluating physical activity and sleep disturbance in axSpA are self-reported questionnaires, which can be impacted by patient recall (reporting bias). One objective measure, polysomnography, has been employed to evaluate sleep in patients with axSpA; however, it is an intrusive measure and cannot be used over the long term. More convenient objective measures are therefore needed to allow for the long-term assessment of both sleep and physical activity in patients\u27 daily lives. Wearable technology that utilizes actigraphy is increasingly being used for the objective measurement of physical activity and sleep in various therapy areas, as it is unintrusive and suitable for continuous tracking to allow longitudinal assessment. Actigraphy characterizes sleep disruption as restless movement while sleeping, which is particularly useful when studying conditions such as axSpA in which chronic pain and discomfort due to stiffness may be evident. Studies have also shown that actigraphy can effectively assess the impact of disease on physical activity. More research is needed to establish the usefulness of objective monitoring of sleep and physical activity specifically in axSpA patients over time. This review summarizes the current perspectives on physical activity and sleep quality in patients with axSpA, and the possible role of actigraphy in the future to more accurately evaluate the impact of treatment interventions on sleep and physical activity in axSpA.Funding: Novartis Pharmaceuticals Corporation.Plain Language Summary: Plain language summary available for this article

Sexual quality of life in patients with axial spondyloarthritis

Paper I, paper II and paper III are excluded from the dissertation due to copyright.Accepted versions of paper II and paper III follow as separate files.Background: Research on the impact of health status on sexual activity and sexual quality of life (QOL) in patients with axial spondyloarthritis (axSpA) is scarce. Aim: The overall aim of the studies was to examine the impact of health status on sexual activity and sexual QOL in male and female patients with axSpA. Methods: Three hundred and seventy-nine consecutive patients with axSpA, aged 18–81 years, who visited the outpatient rheumatology clinics at two Norwegian hospitals were included. Data on demographic factors, disease, treatment, and lifestyle variables were collected by doctors and nurses from questionnaires, laboratory test results, direct interviews, and physical examinations, at the baseline and after 5 years. At the followup, 245 patients participated. A broad-spectrum data collection method was used to obtain data for demographics, patient-reported outcome measures (PROMS), and disease activity/damage. PROMS measures included the Health Assessment Questionnaire (HAQ), Bath Ankylosing Spondylitis Patients Global Score (BAS-G), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Activity Index (BASDAI), 15D Measure of Health-Related Quality of Life (15D), Health Survey Short-Form-36 items (SF-36), and Sexual Quality of Life–Female (SQOL-F). Data on disease activity and damage were obtained from the Bath Ankylosing Spondylitis Metrology Index (BASMI) and the Maastricht Ankylosing Spondylitis Enthesis Score (MASES). Conclusions: This cohort of outpatient patients with axSpA reported a low impact of health status on sexual activity and sexual QOL. Sexual QOL did not seem to worsen over time and remained stable through the 5-year follow-up despite an increase in the number of comorbidities. Effective disease control and changes in healthy lifestyle habits may help to improve the outcomes for these patients.publishedVersio

Assessing disease activity and response to treatment in axial spondyloarthritis: The unmet clinical need and potential role for quantitative imaging

BACKGROUND: Objective assessments of disease activity and response to treatment in axial spondyloarthritis (axSpA) remain an area of unmet clinical need. Quantitative magnetic resonance imaging (qMRI) offers potential for more accurate measures of disease activity and therapeutic response. PURPOSE: To critically appraise current methods of disease activity in axSpA and determine the responsiveness and validity of quantitative imaging biomarkers (QIBs) in patients with axSpA undergoing biologic therapy. METHODS: An observational cohort study was carried out to assess the specificity of our current disease activity measure on patients with axSpA. A systematic literature review was performed to assess the use of MRI in the assessment of axSpA. A prospective cohort study was carried out on 30 patients with axSpA undergoing biologic therapy or switching biologic therapy. Conventional and qMRI scans, including diffusion-weighted imaging (DWI) and chemical shift-encoded imaging (CSI) were carried out at baseline and after 12-16 weeks of treatment. Apparent diffusion coefficient (ADC) and proton density fat fraction (PDFF) maps were analysed using the partially-automated Bone Edema and Adiposity Characterisation with Histograms (BEACH) tool, which derives a series of quantitative imaging biomarkers (QIBs) for both ADC and PDFF. Conventional MR images were assessed using established visual scoring methods. QIBs were assessed in terms of change after treatment and correlation with clinical and conventional MRI measures of disease activity. RESULTS: Current disease activity measures are not specific to axSpA and can be increased in a number of other spinal pathologies. ADC biomarkers are sensitive to changes in inflammation and show significant reductions following biologic therapy, while PDFF-based QIBs showed nonsignificant reductions. Responsiveness to therapy was moderate for ADC based biomarkers and small for conventional scoring systems. ADC and PDFF correlated well with conventional MRI scoring methods. CONCLUSION: Quantitative MRI offers promise for a more accurate assessment of disease activity in axSpA

Assessment by doppler ultrasound of entheseal lesions in spondyloarthritis : a longitudial study to determine structural damage and disease activity lesions

RESUMO: Enthesitis is the hallmark of spondyloarthritis (SpA), and is observed in all subtypes. Wide information on SpA abnormalities, including synovitis, tendinitis and enthesitis, can be efficiently perceived by Doppler ultrasound. Furthermore, several studies on imaging of enthesis showed that imaging techniques are better than clinical examination to detect enthesis alterations; and vascularized enthesitis detected by Doppler ultrasound appears to be a valuable diagnostic tool to confirm SpA diagnosis. However, data published until now concerning entheseal elementary alterations that characterize SpA enthesitis (enthesis inflammatory activity) or enthesopathy (permanent structural changes) reflect rather the authors’ empiric opinion than a methodological validation process. In this sense it seems crucial to identify elementary entheseal lesions associated with activity or damage, in order to improve monitoring and treatment response in SpA patients. The development of better assessment tools is today a challenge and a need in SpA. The first study of this thesis focused on the analysis of the reliability of inter-lector and inter-ultrasonography equipment of Madrid sonography enthesitis index (MASEI). Fundamental data for the remaining unrolling project validity. In the second and third studies we concerned about two entheseal elemental lesions: erosions and bursa. In literature erosions represent a permanent structural damage, being useful for monitoring joint injury, disease activity and therapeutic response in many rheumatic diseases; and to date, this concept has been mostly applied in rheumatoid arthritis (RA). Unquestionably, erosion is a tissue-related damage and a structural change. However, the hypothesis that we decided to test was if erosions represent a permanent structural change that can only grow and worsen over time, as occurs in RA, or a transitory alteration. A longitudinal study of early SpA patients was undertaken, and the Achilles enthesis was used as a model. Our results strongly suggested that previously detected erosions could disappear during the course of the disease, being consistent with the dynamic behavior of erosion over time. Based on these striking results it seems reasonable to suggest that the new-bone formation process in SpA could be associated with the resolution of cortical entheseal erosion over time. These results could also be in agreement with the apparent failure of anti-tumor necrosis factor (TNF) therapies to control bone proliferation in SpA; and with the relation of TNF-α, Dickkopf-related protein 1 (Dkk-1) and the regulatory molecule of the Wnt signaling pathway in the bone proliferation in SpA. In the same model, we then proceeded to study the enthesis bursa. Interestingly, the Outcome Measures in Rheumatology Clinical Trials (OMERACT) enthesopathy definition does not include bursa as an elementary entheseal lesion. Nonetheless, bursa was included in 46% of the enthesis studies in a recently systematic literature review, being in agreement with the concept of “synovio-entheseal complex” that includes the link between enthesitis and osteitis in SpA. It has been clarified in recent data that there is not only a close functional integration of the enthesis with the neighboring bone, but also a connection between enthesitis and synovitis. Therefore, we tried to assess the prevalence and relevance of the bursa-synovial lesion in SpA. Our findings showed a significant increase of Achilles bursa presence and thickness in SpA patients compared to controls (healthy/mechanical controls and RA controls). These results raise awareness to the need to improve the enthesopathy ultrasonographic definition. In the final work of this thesis, we have explored new perspectives, not previously reported, about construct validity of enthesis ultrasound as a possible activity outcome in SpA. We performed a longitudinal Achilles enthesis ultrasound study in patients with early SpA. Achilles ultrasound examinations were performed at baseline, six- and twelve-month time periods and compared with clinical outcome measures collected at basal visit. Our results showed that basal erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are higher in patients with Doppler signal in enthesis, and even that higher basal ESR, CRP and Ankylosing Spondylitis Disease Activity Score (ASDAS) predicted a higher Doppler signal (an ultrasound alteration accepted as representative of inflammation) six months later. Patients with very high disease activity assessed by ASDAS (>3.5) at baseline had significantly higher Achilles total ultrasound score verified at the same time; and ASDAS <1.3 predicted no Doppler signal at six and twelve months. This seems to represent a connection between classical biomarkers and clinical outcomes associated with SpA activity and Doppler signal, not only at the same time, but also for the following months. Remarkably, patients with inactive disease (ASDAS < 1.3) at baseline had no Doppler signal at six and twelve months. These findings reinforce the potential use of ultrasound related techniques for disease progression assessment and prognosis purposes. Intriguingly, Ankylosing Spondylitis Disease Activity Index (BASDAI) didn’t show significant differences between different cut-offs concerning ultrasound lesions or Doppler signal, while verified with ASDAS. These results seem to indicate that ASDAS reflects better than BASDAI what happens in the enthesis. The work herein discussed clearly shows the potential utility of ultrasound in enthesis assessment in SpA patients, and can be important for the development of ultrasound activity and structural damage scores for diagnosis and monitoring purposes. Therefore, local promotion of this technique constitutes a medical intervention that is worth being tested in SpA patients for diagnosis, monitoring and prognosis purposes

Human motion capture for movement limitation analysis using an RGB-D camera in spondyloarthritis: a validation study

A human motion capture system using an RGB-D camera could be a good option to understand the trunk limitations in spondyloarthritis. The aim of this study is to validate a human motion capture system using an RGB-D camera to analyse trunk movement limitations in spondyloarthritis patients. Cross-sectional study was performed where spondyloarthritis patients were diagnosed with a rheumatologist. The RGB-D camera analysed the kinematics of each participant during seven functional tasks based on rheumatologic assessment. The OpenNI2 library collected the depth data, the NiTE2 middleware detected a virtual skeleton and the MRPT library recorded the trunk positions. The gold standard was registered using an inertial measurement unit. The outcome variables were angular displacement, angular velocity and lineal acceleration of the trunk. Criterion validity and the reliability were calculated. Seventeen subjects (54.35 (11.75) years) were measured. The Bending task obtained moderate results in validity (r=0.55–0.62) and successful results in reliability (ICC=0.80–0.88) and validity and reliability of angular kinematic results in Chair task were moderate and (r=0.60–0.74, ICC=0.61–0.72). The kinematic results in Timed Up and Go test were less consistent. The RGB-D camera was documented to be a reliable tool to assess the movement limitations in spondyloarthritis depending on the functional tasks: Bending task. Chair task needs further research and the TUG analysis was not validated.Funding for open access charge: Universidad de Málaga/CBUA. Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature

Clinical applications of lumbar paraspinal mechanical properties and lumbopelvic kinematics in subjects with mechanical and inflammatory low back pain

El dolor lumbar (Low Back Pain, LBP) es uno de los trastornos musculoesqueléticos más comunes, que afecta al 80% de la población en algún momento de su vida. Atendiendo a su patrón clínico, suele clasificarse como mecánico o inflamatorio y se asocia con cambios en la actividad neuromuscular, disminución de la movilidad de la columna, flexibilidad muscular lumbar limitada o cinemática espinal alterada. La creciente prevalencia del LBP requiere una mejor comprensión de la etapa aguda/subaguda de la patología para optimizar el diagnóstico y el tratamiento y así minimizar su carga socio-económica. El objetivo general fue profundizar en la descripción y la relevancia clínica de las Propiedades Mecánicas Musculares (Muscle Mechanical Properties, MMPs) de la musculatura espinal y la cinemática lumbopélvica en sujetos con espondiloartritis axial (axSpA), dolor lumbar agudo (acute LBP), subagudo (Subacute LBP, sLBP) y controles. Los objetivos específicos contemplaban identificar diferencias en las MMPs a nivel lumbar y cervical entre sujetos con axSpA, sLBP y controles. Identificar asociaciones entre MMPs y variables sociodemográficas y clínicas. Identificar los cambios de dichas propiedades tras realizar una secuencia estandarizada de movimientos y determinar la influencia del LBP y la edad en dichos cambios. Así como, identificar las diferencias en el ritmo lumbopélvico (Lumbopelvic Rhythm, LPR) entre sujetos con aLBP y controles. La muestra fue reclutada desde el centro privado Physiobalance, el Departamento de Reumatología del Hospital Reina Sofía, y el Campus Biosanitario de la Universidad de Córdoba. Los resultados indicaron que el tono y la rigidez paraespinal fue mayor en patología inflamatoria que en LBP mecánico o sanos (p0.8). Tras movimientos secuenciados, el tono y la rigidez aumentaron 0.37 Hz y 22.75 N/m, respectivamente, en los sujetos jóvenes independientemente de la presencia o ausencia de dolor. La relajación fue mayor en los sujetos jóvenes sanos, así como la fluencia lo fue en sujetos con LBP menores de 35 años. Por último, los sujetos con aLBP mostraron diferencias en el LPR respecto a sanos, presentando durante la flexión, un menor movimiento lumbar en el segundo cuartil (Q2) (p=0.001), y de pelvis y troco durante el tercer (Q3) (p=<.001; p=.001) y cuarto (Q4) cuartil (p=.001; p=.045). Durante la extensión, el tronco y el segmento lumbar en Q2 y Q3 se movieron menos en los sujetos con dolor (p=.030; p=.046 and p=.013; p=.002 respectivamente). En conclusión, las MMPs lumbares y cervicales son diferentes según el tipo de LBP y, al menos en los pacientes con axSpa, se asocian un peor estado y progresión de la enfermedad a mayor tono y rigidez en las regiones lumbar y cervical. Asimismo, el movimiento espinal secuenciado puede modificar el tono y la rigidez paraespinal lumbar según la edad del paciente, pero no según la presencia de LBP. El LPR es diferente entre sujetos con aLBP y sanos. Estos hallazgos permiten afirmar que las MMPs y el LPR son relevantes clínicamente y su evaluación debe realizarse durante el seguimiento del paciente.Low back pain (LBP) is one of the most common musculoskeletal disorders, affecting 80% of the population at some point in their lives. Based on its clinical pattern, it is usually classified as mechanical or inflammatory. It is associated with changes in neuromuscular activity, decreased spinal mobility, limited lumbar muscle flexibility, or altered spinal kinematics. The increasing prevalence of LBP requires a better understanding of the acute/subacute stage of the pathology to optimize diagnosis and treatment and thus minimize its socio-economic burden. The general objective was to deepen the description and clinical relevance of the Muscle Mechanical Properties (MMPs) of the spinal musculature and lumbopelvic kinematics in subjects with axial spondyloarthritis (axSpA), acute low back pain (aLBP), subacute (sLBP) and controls. The specific objectives were to identify differences in MMPs at the lumbar and cervical levels between subjects with axSpA, sLBP, and controls. To identify associations between MMPs and sociodemographic and clinical variables. To identify the changes in these properties after performing a standardized sequence of movements and to determine the influence of LBP and age on these changes. Also, to identify the differences in the Lumbopelvic Rhythm (LPR) between subjects with aLBP and controls. The sample was recruited from the private Physiobalance center, the Rheumatology Department of the Reina Sofia Hospital, and the Biosanitary Campus of the University of Cordoba. The results indicated that paraspinal tone and stiffness were higher in inflammatory pathology than in mechanical or healthy LBP (p0.8). After sequential movements, tone and stiffness increased by 0.37 Hz and 22.75 N/m, respectively, in young subjects irrespective of the presence or absence of pain. Relaxation was greater in young, healthy subjects, as was creep in LBP subjects younger than 35 years. Finally, subjects with aLBP showed differences in the LPR to healthy subjects, presenting during flexion, less lumbar movement in the second quartile (Q2) (p=0.001), and of pelvis and trochus during the third (Q3) (p=<.001; p=.001) and fourth (Q4) quartiles (p=.001; p=.045). During extension, the trunk and lumbar segment in Q2 and Q3 moved less in subjects with pain (p=.030; p=.046 and p=.013; p=.0029, respectively). In conclusion, lumbar and cervical MMPs differ according to LBP type. At least in axSpa patients, worse disease status and progression are associated with greater tone and stiffness in the lumbar and cervical regions. Likewise, sequenced spinal motion can modify lumbar paraspinal tone and stiffness according to patient age but not according to the presence of LBP. The LPR is different between aLBP and healthy subjects. These findings affirm that MMPs and LPR are clinically relevant and that their evaluation should be performed during patient follow-up

Prevalence, physical activity and work in patients with spondyloarthritis

Spondyloarthritis (SpA) is a group of interrelated inflammatory rheumatic diseases with the sub-diagnoses ankylosing spondylitis (AS), psoriatic arthritis (PsA), arthritis-associated inflammatory bowel disease (Aa-IBD), undifferentiated SpA (USpA), where stiffness and pain are key symptoms. Insidious onset back pain, morning stiffness, waking up at night, and improvement from exercise are common characteristics. The disease is life-long, often with early onset, and can cause limitations in physical function, affecting the ability to work, and has a negative effect on health-related quality of life. The overall aim of the present work was to describe the prevalence of SpA and to study the consequences for the individual and society regarding physical activity and work in a population-based cohort of patients seeking health care. The studies are based on a cohort of patients with SpA, identified through the Skåne Health Care Register by searching for 12 ICD-10 codes for SpA that had led to a doctor’s consultation 2003–2007. Two questionnaire surveys in 2009 and 2011 were sent to all the patients in the cohort >18 years and data from these formed the basis of the studies II, III, and IV. Study I: The estimation of SpA prevalence based on almost 4,000 patients was 0.45% in adults (≥ 15 years), and equally common in women and men. The prevalence in different subgroups was 0.12% in AS, 0.25% in PsA, 0.0015% in Aa-IBD, and 0.10% in USpA. Study II dealt with the proportion of patients who met the WHO recommendations for physical activity. Seven out of ten patients with SpA met the recommendations, more frequently in women than in men, and with a somewhat higher proportion in the SpAScania cohort than in the general Swedish population. Studies III and IV examined the patterns of reduced productivity at work both cross-sectionally and longitudinally. Just under half of the patients with SpA reported reduced productivity at work, and more reduction was reported in women than in men. Reduced productivity at work was associated with, and could be predicted from several patient-reported outcome measures (PROMs) such as reduced health-related quality of life (HRQoL), higher disease activity, lower physical function, lower self-efficacy, worse mental health and low education level. To conclude, 45 individuals out of 10,000 have a diagnosis of SpA, and affected individuals report significant consequences of the disease. The findings presented in this thesis could help clinicians to identify patients at an early stage at risk of a worse prognosis using simple clinical questions in routine practice, and tailor the activities, treatment, and care for patients with SpA

Diagnostic imaging techniques and predictive factors in spondyloarthritis and psoriatic arthritis

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Medicina. Fecha de lectura: 12-06-201

Evaluación Ecográfica del Compromiso de Entesis en Pacientes con Espondiloartritis

La entesis es el órgano diana de la inflamación en las espondiloartritis (EspA) siendo clave en su fisiopatogenia. La ecografía está emergiendo como la técnica de preferencia para la detección de entesitis. Se realizó este estudio a fin de describir las características ecográficas del compromiso de las entesis en pacientes con espondiloartritis. Se evaluaron 20 pacientes con diagnóstico de EspA que acudieron al Hospital de Clínicas. Se investigaron variables clínicas y demográficas y posteriormente exploración ecográfica en 12 sitios de entesis hallándose los índices GUESS (Glasgow Enthesitis Scoring System) y MASEI (Madrid Sonographic Enthesitis Index) y posterior correlación de las variables ecográficas con las clínicas.CONACYT - Consejo Nacional de Ciencia y TecnologíaPROCIENCI