The perspective of people with axial spondyloarthritis regarding physiotherapy : room for the implementation of a more active approach

Objectives. Physiotherapy is recommended in the management of people with axial spondyloarthritis (axSpA), with new insights into its preferred content and dosage evolving. The aim of this study was to describe the use and preferences regarding individual and group physiotherapy among people with axSpA. Methods. A cross-sectional survey was conducted among people with axSpA living in The Netherlands (NL) and Switzerland (CH). Results. Seven hundred and thirteen people with axSpA participated (56.7% male, median age 55 years, median Assessment of Spondyloarthritis International Society Health Index score 4.2). Response rates were 45% (n¼206) in NL and 29% in CH (n¼507). Of these participants, 83.3% were using or had been using physiotherapy. Individual therapy only was used or had been used by 36.7%, a combination of individual plus land- and water-based group therapy by 29.1% and group therapy by only 5.3%. Fewer than half of the participants attending individual therapy reported active therapy (such as aerobic, muscle strength and flexibility exercises). Although the majority (75.9%) were not aware of the increased cardiovascular risk, participants showed an interest in cardiovascular training, either individually or in a supervised setting. If supervised, a majority, in CH (75.0%) more than in NL (55.7%), preferred supervision by a specialized physiotherapist. Conclusion. The majority of people with axSpA use or have used physiotherapy, more often in an individual setting than in a group setting. The content of individual therapy should be more active; in both therapy settings, aerobic exercises should be promoted. In particular, enabling people with axSpA to perform exercises independently would meet their needs and might enhance their daily physical activity

Changes in hand and generalised bone mineral density in patients with recent-onset rheumatoid arthritis

Objectives: To evaluate changes in bone mineral density (BMD) in the hands, hip and spine after 1 and 2 years of follow-up, in relation to antirheumatic and antiresorptive therapies and disease and demographic variables in patients with recent-onset rheumatoid arthritis ( RA). Methods: Changes in BMD measured in metacarpals 2-4 by digital x-ray radiogrammetry and in the hip and spine by dual energy x-ray absorptiometry were assessed at baseline and after 1 and 2 years of follow-up in 218 patients with recent-onset RA from the BeSt study, who received one of four treatment strategies: sequential monotherapy ( group 1); step-up combination therapy ( group 2); initial combination therapy with tapered high-dose prednisone ( group 3); or initial combination therapy with infliximab (group 4). Results: After 1 and 2 years, there was significant BMD loss in all locations, with significantly greater BMD loss in the hands than generalised BMD loss in the hip and spine. Initial combination therapy with prednisone or infliximab were associated with less hand BMD loss compared with initial monotherapy after 1 and 2 years (-0.9 and -1.6%, -0.6 and -1.4%, -1.7 and -3.3%, and -2.6 and -3.6% for group 4-1 after 1 and 2 years, overall p = 0.001 and p = 0.014, respectively). Progression in erosions was independently associated with increased BMD loss both in the hands and hip after 1 year. The use of bisphosphonates protected only against generalised BMD loss in the hip and spine. Conclusions: The association between joint damage progression and both hand and generalised BMD loss in RA suggests common pathways between these processes, with hand BMD loss occurring earlier in the disease course than generalised BMD los

An Increase of the Character Function of Self-Directedness Is Centrally Involved in Symptom Reduction during Remission from Major Depression

Background. Studies with the Temperament and Character Inventory (TCI) in depressive disorders have shown changes (Δ) of the character of Self-Directedness (SD) and the temperament of Harm Avoidance (HA). The central question of this study is which of these two changes is most proximally related to the production of depressive symptoms. Methods. The start and endpoint data from a two-year followup of 58 depressed patients were reanalyzed. We used the ΔHA and ΔSD scores as well as the Δ scores on three dimensions of psychopathology, called Emotional Dysregulation (ED), Retardation (RET), and Anxiety (ANX). The presence of the main relation between personality and psychopathology was tested in all patients and in four subcategories. The data were analyzed by MANCOVA and Structural Equation Modelling (SEM). Results. ΔHA and ΔSD correlated negatively, and only ΔSD was related (negatively) to ΔED. This pattern was found in all subcategories. SEM showed ΔHA and ΔSD had an ambiguous causal interrelationship, while ΔSD, ΔRET, and ΔANX had unidirectional effects on ΔED. Conclusion. The results correspond with a central pathogenetic role for a state-related deficit at the character level in depression. This may have important consequences for investigations of endophenotypes and clinical treatment

Being as Normal as Possible: How Young People Ages 16–25 Years Evaluate the Risks and Benefits of Treatment for Inflammatory Arthritis

Objective To explore how young people (ages 16–25 years) with inflammatory arthritis evaluate the risks and benefits of treatment, particularly treatment with biologic therapies. Methods This qualitative study involved in-depth interviews (n = 44) with young people, trusted others (e.g., parents), and health professionals; audio-recordings (n = 4) of biologic therapy–related consultations; and focus groups (n = 4). Analysis used techniques from grounded theory (open and focused coding, constant comparison, memoing, and mapping). Results Young people aspired to live what they perceived as a “normal” life. They saw treatment as presenting both an opportunity for and a threat to achieving this. Treatment changes were therefore subject to complex and ongoing evaluation, covering administration, associated restrictions, anticipated effects, and side effects. Information sources included expert opinion (of professionals and other patients) and personal experience. Previous treatments provided important reference points. Faced with uncertain outcomes, young people made provisional decisions. Both trusted others and health professionals expressed concern that young people were too focused on short-term outcomes. Conclusion Young people value treatment that helps them to live a “normal” life. There is more to this than controlling disease. The emotional, social, and vocational consequences of treatment can be profound and lasting: opportunities to discuss the effects of treatment should be provided early and regularly. While making every effort to ensure understanding of the long-term clinical consequences of taking or not taking medication, the wider impact of treatment should not be dismissed. Only through understanding young people's values, preferences, and concerns can a sustainable balance between disease control and treatment burden be achieved

Hierarchical network structure as the source of power-law frequency spectra (state-trait continua) in living and non-living systems: how physical traits and personalities emerge from first principles in biophysics

What causes organisms to have different body plans and personalities? We address this question by looking at universal principles that govern the morphology and behavior of living systems. Living systems display a small-world network structure in which many smaller clusters are nested within fewer larger ones, producing a fractal-like structure with a power-law cluster size distribution. Their dynamics show similar qualities: the timeseries of inner message passing and overt behavior contain high frequencies or 'states' that are nested within lower frequencies or 'traits'. Here, we argue that the nested modular (power-law) dynamics of living systems results from their nested modular (power-law) network structure: organisms 'vertically encode' the deep spatiotemporal structure of their environments, so that high frequencies (states) are produced by many small clusters at the base of a nested-modular hierarchy and lower frequencies (traits) are produced by fewer larger clusters at its top. These include physical as well as behavioral traits. Nested-modular structure causes higher frequencies to be embedded in lower frequencies, producing power-law dynamics. Such dynamics satisfy the need for efficient energy dissipation through networks of coupled oscillators, which also governs the dynamics of non-living systems (e.g. earthquake dynamics, stock market fluctuations). Thus, we provide a single explanation for power-law frequency spectra in both living and non-living systems. If hierarchical structure indeed produces hierarchical dynamics, the development (e.g. during maturation) and collapse (e.g. during disease) of hierarchical structure should leave specific traces in power-law frequency spectra that may serve as early warning signs to system failure. The applications of this idea range from embryology and personality psychology to sociology, evolutionary biology and clinical medicine

Droom van een historische werkelijkheid

[No abstract available

Health-related quality of life and functional ability in patients with early arthritis during remission steered treatment: results of the IMPROVED study

INTRODUCTION: The aim of this study was to investigate patient reported outcomes (PROs) of functional ability and health related quality of life (HRQoL) in patients with early (rheumatoid) arthritis during one year of remission steered treatment. METHODS: In this study, 610 patients with early rheumatoid arthritis (RA) or undifferentiated arthritis (UA) were treated with methotrexate (MTX) and tapered high dose of prednisone. Patients in early remission (Disease Activity Score (DAS) <1.6 after 4 months) tapered prednisone to zero and when in persistent remission, also tapered MTX. Patients not in early remission were randomized to either MTX + hydroxychloroquine + sulphasalazine + prednisone (arm 1) or to MTX + adalimumab (arm 2). Every 4 months, patients filled out the Health Assessment Questionnaire (HAQ) and the McMaster Toronto Arthritis Patient Preference Questionnaire (MACTAR), the Short Form 36 (SF-36) and visual analogue scales (VAS). Change scores were compared between treatment groups. The association with achieving remission was analyzed using linear mixed models. RESULTS: During year 1, patients who achieved early remission had the most improvement in PROs with scores comparable to the general population. Patients in the randomization arms showed less improvement. Scores were comparable between the arms. There was a significant association between achieving remission and scores of HAQ, MACTAR and physical HRQoL. CONCLUSIONS: In early arthritis, PROs of functional ability and HRQoL after one year of remission steered treatment reach normal values in patients who achieved early remission. In patients not in early remission, who were randomized to two strategy arms, PROs improved less, with similar scores in both treatment arms. TRIAL REGISTRATIONS: ISRCTN11916566 and EudraCT2006-006186-1

Drug-free remission, functioning and radiographic damage after 4 years of response-driven treatment in patients with recent-onset rheumatoid arthritis

0.05, group 4 versus groups 1 and 2, group 3 versus group 2). Conclusions: In patients with recent-onset active RA, drug-free remission was achieved in up to 18% of patients. DAS-driven treatment maintained clinical and functional improvement, independent of the treatment strategy. Joint damage progression remained significantly lower after initial combination therapy compared with initial monotherap

Pharmacological fMRI; a clinical exploration

Dit proefschrift beschrijft de resultaten van een verkennend onderzoek naar een nieuwe techniek die gebruikt kan worden om de effecten van geneesmiddelen op hersenaktiviteit af te beelden: pharmacologische functionele magnetic resonance imaging (farmacologische fMRI of phMRI). Met behulp van deze techniek werden de effecten onderzocht van drie verschillende medicijnen (de bètablokker propranolol, de selectieve oestrogeen-receptor modulator (SERM) raloxifene en de cholinesteraseremmer galantamine) op hersenaktiviteit van respectievelijk gezonde jongere en oudere controles, en patiënten met geheugenklachten. Aan de hand van de resultaten van dit onderzoek werd nagegaan in hoeverre phMRI toepasbaar zou kunnen zijn in een klinische context. De MRI scanner is al bijna 30 jaar een vast onderdeel van het instrumentarium van radiologen. MRI is een volledig non-invasieve scantechniek die artsen in staat stelt om haarscherpe, driedimensionale afbeeldingen te maken van de verschillende organen van levende patiënten en de eventuele ziekteprocessen die zich daarin afspelen. fMRI is een meer recente toepassing van MRI, waarbij de wisselende magnetische eigenschappen van de rode bloedkleurstof ‘hemoglobine’ worden benut om zwart-wit contrast te geven aan MR plaatjes (Jezzard et al., 2001). Afhankelijk van de mate waarin hersengebieden aktief zijn wordt een sterker of minder sterk bloed-oxygenatie afhankelijk (BOLD) MR signaal gemeten. De meeste fMRI studies vergelijken de gemiddelde signaalintensiteiten van hersengebieden tussen actieve en een minder actieve condities van een bepaalde taak, die tijdens het scannen wordt uitgevoerd. Dit levert driedimensionaal plaatjes op van het hele brein, waarin de gemiddelde intensiteitsverschillen tussen twee taak-condities zijn af te lezen (“contrast plaatjes”). phMRI is een verdere nuancering van fMRI, waarbij contrastplaatjes worden onderzocht op toenames of afnames van intensiteitsverschillen als gevolg van blootstelling aan een bepaalde farmacologische stof. Aangezien de meeste psychotrope geneesmiddelen aangrijpen in specifieke neurotransmittersystemen zou phMRI gebruikt kunnen worden om de toestand van deze systemen te onderzoeken in de gezonde en de zieke situatie. phMRI zou dus eventueel als klinisch-diagnostisch instrument kunnen worden gebruikt. Er is echter nog maar weinig onderzoek gedaan naar de klinische waarde van phMRI (Honey and Bullmore, 2004). Dit proefschrift had tot doel dit terrein verder te verkennen. Patiënten en proefpersonen werden gescand met behulp van fMRI tijdens het uitvoeren van speciaal voor dit onderzoek ontwikkelde geheugentestjes (paradigmata). Hierdoor waren we in staat om hersengebieden zichtbaar te maken die betrokken zijn bij verschillende aspecten van geheugenfunctie. De effecten van geneesmiddelen werden onderzocht op hersenfunctie zoals die werd opgeroepen door bovengenoemde taken. We gebruikten achtereenvolgens een ‘face-encoding’ taak (onthouden van onbekende menselijke gezichten (Small et al., 1999)), een ‘face-recognition’ taak (herkennen van eerder getoonde gezichten), en een n-letter back werkgeheugen taak (tijdelijke opslag van nieuwe informatie (Owen et al., 2005)). Verder werd in samenwerking met Dr. A.H. van Stegeren and Prof. Dr. W.TA.M. Everaerd van de afdeling Klinische en Experimentele Psychologie van de Universiteit van Amsterdam het International Affective Picture System (IAPS) (Lang and Bradley, 1997), aangepast voor gebruik in de MR scanner. Deze taak had tot doel hersengebieden te aktiveren die betrokken zijn bij de opslag van emotioneel negatief geladen (onprettige) informatie. fMRI analyses werden gedaan met de fMRI expert analysis tool (FEAT) uit het data-analyse pakket fMRIB software library (FSL) (Smith et al., 2004). Ons onderzoek leverde de volgende bevindingen op: 1. Effecten van verschillende geneesmiddelen op hersenfunctie bij mensen kunnen worden gemeten met behulp van fMRI, maar zijn vrij klein. 2. Onze bevindingen sluiten aan bij die van ander fMRI onderzoek waaruit blijkt dat de effecten van geneesmiddelen op hersenfunctie regio-specifiek en proces-specifiek kunnen zijn (Honey and Bullmore, 2004). 3. De effecten van geneesmiddelen op hersenfunctie zijn tevens geslachts- en ziekte-(stadium)-specifiek. 4. Deze effecten zijn afhankelijk van de duur van blootstelling aan het farmacologische agens. 5. In het geval van cholinerge stimulatie leidde een éénmalige stootdosis galantamine al tot regio- proces- en ziektespecifieke effecten. 6. We hebben een methode ontwikkeld om de effecten van geneesmiddelen op hersenfunctie tijdens geheugenfunctie te onderzoeken in relatie tot gedragsveranderingen en specifieke hersenprocessen. 7. Indien grote groepen patiënten geïncludeerd worden zijn uitgebreide studies naar de klinische (vroegdiagnostische en predictieve) waarde van de gemeten effecten zeer goed mogelijk. phMRI is voorlopig nog een onderzoeksinstrument. Vanuit klinisch oogpunt kunnen de bevindingen van phMRI studies echter erg interessant zijn. Studies van de regio- en proces-specificiteit van geneesmiddelen kunnen helpen bij het ontwikkelen van geneesmiddelen die meer gericht inwerken op specifieke hersenprocessen. Dit zou mogelijk de effectiviteit van geneesmiddelen kunnen verhogen en het aantal bijwerkingen kunnen verminderen. phMRI kan verder worden ingezet om het werkingsmechanisme van psychotrope geneesmiddelen te onderzoeken. phMRI provokatietests laten bovendien zien dat de onmiddellijke effecten van geneesmiddelen een vroeg-diagnostische waarde kunnen hebben, en misschien zelfs het succes van farmacotherapie kunnen voorspellen (Fu et al., 2004). Toekomstig onderzoek zal moeten uitwijzen in hoeverre phMRI in staat is om klinisch relevante functionele biomarkers aan te tonen in individuele patiënten. Ondertussen kunnen groepsstudies al resultaten leveren die van klinisch belang zouden kunnen zijn voor individuele patiënten. Met phMRI provokatietests kunnen relaties worden gelegd tussen bepaalde klinische verschijnselen en een afwijkende reactiviteit van centrale neurotransmittersystemen. Zijn zulke relaties eenmaal gelegd, dan kunnen patiënten die zich presenteren met de bewuste symptomen of afwijkingen worden behandeld met een gerichte farmacotherapie. De ontwikkelingen in de methodologie van fMRI staan ondertussen niet stil. Er is inmiddels een arsenaal aan nieuwe analysemethoden beschikbaar gekomen, die van belang zouden kunnen zijn voor toekomstig phMRI onderzoek. Ook al staat farmacologische fMRI nog in de kinderschoenen, er wordt met grote stappen vooruitgang geboekt. Het is dus waarschijnlijk dat phMRI, in combinatie met andere technieken, een belangrijk bijdrage zal gaan leveren aan de zoektocht naar biologische markers met een bruikbare klinische waarde. Reference List Fu CHY, Williams SCR, Cleare AJ, Brammer MJ, Walsh ND, Kim J, Andrew CM, Pich EM, Williams PM, Reed LJ, Mitterschiffthaler MT, Suckling J, Bullmore ET. Attenuation of the neural response to sad faces in major depression by antidepressant treatment - A prospective, event-related functional magnetic resonance imaging study. Archives of General Psychiatry 2004; 61:877-889. Honey G, Bullmore E. Human pharmacological MRI. Trends in Pharmacological Sciences 2004; 25:366-374. Jezzard P, Matthews PM, Smith SM. Functional MRI - An introduction to methods. New York: Oxford University Press, 2001. Lang PJ, Bradley MM. International affective picture system (IAPS); Technical manual and affective ratings. NIMH Center for the study of emotion and attention 1997. Owen AM, McMillan KM, Laird AR, Bullmore E. N-back working memory paradigm: A meta-analysis of normative functional neuroimaging. Hum.Brain Mapp. 2005; 25:46-59. Small SA, Perera GM, DeLaPaz R, Mayeux R, Stern Y. Differential regional dysfunction of the hippocampal formation among elderly with memory decline and Alzheimer's disease. Annals of Neurology 1999; 45:466-472. Smith SM, Jenkinson M, Woolrich MW, Beckmann CF, Behrens TEJ, Johansen-Berg H, Bannister PR, De Luca M, Drobnjak I, Flitney DE, Niazy RK, Saunders J, Vickers J, Zhang YY, De Stefano N, Brady JM, Matthews PM. Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage 2004; 23:S208-S219.Barkhof, F. [Promotor]Scheltens, P. [Promotor]Rombouts, S.A.R.B. [Copromotor

Interpretation of DAS28 and its components in the assessment of inflammatory and non-inflammatory aspects of rheumatoid arthritis

Background: DAS28 is interpreted as the inflammatory disease activity of RA. Non-inflammatory pain mechanisms can confound assessment. We aimed to examine the use of DAS28 components or DAS28-derived measures that have been published as indices of non-inflammatory pain mechanisms, to inform interpretation of disease activity. Methods: Data were used from multiple observational epidemiology studies of people with RA. Statistical characteristics of DAS28 components and derived indices were assessed using baseline and follow up data from British Society for Rheumatology Biologics Registry participants [1] commencing anti-TNF therapy (n = 10813), or [2] changing between non-biologic DMARDs (n=2992), [3] Early Rheumatoid Arthritis Network participants (n=813), and [4] participants in a cross-sectional study exploring fibromyalgia and pain thresholds (n=45). Repeatability was tested in 34 patients with active RA. Derived indices were the proportion of DAS28 attributable to patient-reported components (DAS28-P), tender-swollen difference and tender:swollen ratio. Pressure pain detection threshold (PPT) was used as an index of pain sensitisation. Results: DAS28, tender joint count, visual analogue scale, DAS28-P, tender-swollen difference and tender:swollen ratio were more strongly associated with pain, PPT and fibromyalgia status than were swollen joint count or erythrocyte sedimentation rate. DAS28-P, tender-swollen difference and tender:swollen ratio better predicted pain over 1 year than did DAS28 or its individual components. Conclusions: DAS28 is strongly associated both with inflammation and with patient-reported outcomes. DAS28-derived indices such as tender-swollen difference are associated with non-inflammatory pain mechanisms, can predict future pain and should inform how DAS28 is interpreted as an index of inflammatory disease activity in RA