Background: Patients and clinicians report pain and fatigue as key outcome measures in rheumatoid arthritis. Fatigue and pain are a major concern to patients. Aim: The objective of this study was to examine fatigue and pain in adult patients with rheumatoid arthritis (RA) and to investigate the association between pain and fatigue with body awareness, demographic, disease-related, emotional and psychosocial factors. Method: Data were collected from a sample of patients with RA (n= 120) recruited from a Rheumatology clinic in a large university hospital in Stockholm, Sweden. Eligible for inclusion were patients between 20 -80 years of age and with a confirmed diagnosis of RA. Fatigue was measured using the Multidimensional Assessment of Fatigue (MAF) scale, while the Visual Analogue Scale (VAS) was used to assess components of pain. A multiple stepwise regression analysis was performed to evaluate factors related to fatigue and pain. In the first step a univariate analysis of variance (ANOVA) was used for all relevant independent factors. In the next step backwards stepwise regression was applied. Result: Fatigue was significantly associated with the Disease Activity Score 28-joints (DAS 28) (p = 0.049), the Body Awareness Questionnaire (BAQ) (p = 0.006), the Positive Affect (PA) scale (p = 0.008) and no smoking (p = 0.021). Pain was significantly associated with the EuroQol EQ-5D (p = 0.008) and the DAS 28 (p = 0.001). The adjusted R-square was 28.6% for fatigue and 50.0% for pain. Conclusion: This study clearly demonstrates that fatigue and pain in patients with RA appear to be associated with disease-related factors. Furthermore, fatigue was related to body awareness and emotional factors, and pain was related to health related quality of life.

Rheumatoid Arthritis (RA) is an autoimmune disease characterized by inflammation and eventual destruction of the synovial joints. The role of platelets in the pathophysiology of arthritis has only recently been established. Because antibodies to CD44 can deplete platelets, we hypothesized that these antibodies might be effective in arthritis through a platelet-depletion mechanism. We examined the K/BxN passive transfer mouse model of arthritis and found that most antibodies against CD44 were capable of depleting platelets. However, anti-CD44 treatment is effective when administered during developing arthritis, while anti-platelet treatment was not. While CD44 antibodies may be therapeutic through platelet-dependant and independent mechanisms, the ability of CD44 antibodies to decrease platelet counts does not seem to be the critical factor in resolving arthritis in the K/BxN model.

Chronic physical illnesses, such as rheumatoid arthritis (RA), that are painful and disabling not only impact on a person’s ability to complete normal daily activities (e.g. dressing, bathing, walking etc.) but may also have a negative impact on psychological well-being. Although a large number of prospective observational studies have examined psychological well-being in RA, none has used appropriate statistical techniques to examine variability in change over time at the individual level. The overarching aim of this dissertation is to use advanced quantitative methods to examine how psychological well-being in RA changes over the course of the disease; and to identify demographic, clinical and psychosocial factors that influence how the disease affects psychological well-being. This aim is addressed via a programme of research with three objectives: (i) to describe patterns of change in psychological well-being during the RA disease course; (ii) to quantify the association between psychological well-being and somatic symptoms; and (iii) to investigate the impact of illness cognitions and coping on psychological well-being. The programme of research consists mainly of analysis of a subsample of data collected as part of the Early RA Study (ERAS, N = 784), an ongoing observational study of RA patients followed prospectively from first presentation to a rheumatologist. A major problem relating to the assessment of psychological distress in individuals with chronic physical illness is the overlapping symptomatology with depression. An examination of the factorial validity of the Hospital Anxiety and Depression Scale (HADS), in the ERAS cohort, indicated the presence of a bifactor structure. Specifically, a general distress factor along with orthogonal (autonomic) anxiety and (anhedonic) depression factors was found to provide the optimal empirical explanation of the covariance in item responses. Further analysis, revealed that responses to one of the depression items were biased by disease severity. However, the magnitude of this bias was negligible, confirming the suitability of this tool in RA populations. For the ERAS cohort, general psychological distress was observed to reduce rapidly early in the course of the disease, stabilising after around two to three-years. However, further analysis suggested that subgroups with distinct longitudinal patterns of distress were present within the sample. Confirming observations in other disease groups, four distinct longitudinal patterns of distress were identified: resilient, chronic distress, delayed distress and recovered. Interestingly, changes in distress were related to self-reported somatic symptoms but not serological markers of disease activity. Building on these findings, analyses that jointly modelled changes in psychological distress with changes in the common somatic symptoms of pain and functional limitation revealed strong cross-sectional and longitudinal associations. This extends the findings of previous research by showing the importance of considering the impact of the disease course on the underlying trajectory of distress. Due to the lack of psychosocial data available in the ERAS cohort a further prospective study, involving 230 RA patients, was conducted to examine the influence of illness cognitions and coping on the affect of the disease on psychological well-being over a period of 6-months. Coping was not found to be related to changes in psychological well-being. Analysis revealed two groupings of patients with similar patterns of illness cognitions that were labelled adapters and non-adapters. Furthermore, cognitions concerning the attribution of symptoms to RA and the perceived personal consequences of their condition were related to changes in psychological distress, even after controlling for demographic and clinical characteristics; and there was some indication that a higher reported level of understanding of their condition was related to increased future positive outlook. In conclusion, the findings of this programme of research highlight the need for the early identification and treatment of RA, not only to slow the progression of the disease but also to maintain or improve psychological well-being. Early treatment is currently focused on pharmaceutical interventions. A tailored psychosomatic approach to treatment involving the skills of a wide range of health professionals, such as nurses, physiotherapists, occupational therapists and psychologists is likely to improve outcomes in RA.

No description available.

Aims: The overall aim of this thesis was to further our understanding of extensor muscles and their role for hand function. The aims of the studies were: To develop and evaluate a new device for finger extensor force measurements. To evaluate ultrasound as a tool for assessment of muscle architecture. To determine the correlation between extensor muscle force and hand function. To evaluate the degree of impaired finger extensor force in rheumatoid arthritis (RA) and the correlation to impaired... mer hand function. To analyse the effect of hand exercise in RA patients and healthy subjects with ultrasound and finger extension force measurements. Method: A new finger extension force measuring device was developed and an ultrasound based method was used to be able to objectively measure the finger extension force and analyze the static and dynamic extensor muscle architectures. Measurements were made of healthy volunteers (n=127) and RA patients (n=77) during uninfluenced and experimental conditions. A hand exercise program was performed and evaluated with hand force measurements, hand function test, patient relevant questionnaires (DASH and SF-36) and ultrasound measurements. Results: The new finger extension force measurement device was developed and then validated with measurements of accuracy as well as test-retest reliability. The coefficient of variation was 1.8 % of the applied load, and the test-retest reliability showed a coefficient of variation no more than 7.1% for healthy subjects. Ultrasound examination on m. extensor digitorum communis (EDC) showed significant differences between healthy men and healthy women as well as between healthy women and RA patients. The extension and flexion force improved in both groups after six weeks of hand exercise (p<0.01). Hand function improved in both groups (p<0.01). The RA group showed improvement in the results of the DASH questionnaire (p<0.05). The cross-sectional area of the EDC increased significantly in both groups. Conclusions: A new finger extension force measuring device has been developed which provides objective and reliable data on the extension force capacity of normal and dysfunctional hands and is sufficiently sensitive to evaluate the effects of hand exercise. US provide useful information about muscle architecture. A significant improvement of hand strength and hand function in RA patients was seen after six weeks of hand training, the improvement was even more pronounced after 12 weeks. Hand exercise is thus an effective intervention for RA patients, providing better strength and function.

Rheumatoid arthritis (RA) is a chronic, destructive, inflammatory arthritis that places significant burden on the individual and society. This thesis represents the most comprehensive effort to date to determine the accuracy of administrative data for detecting RA patients; and describes the development and validation of an administrative data algorithm to establish a province-wide RA database. Beginning with a systematic review to guide the conduct of this research, two independent, multicentre, retrospective chart abstraction studies were performed amongst two random samples of patients from rheumatology and primary care family physician practices, respectively. While a diagnosis by a rheumatologist remains the gold standard for establishing a RA diagnosis, the high prevalence of RA in rheumatology clinics can falsely elevate positive predictive values. It was therefore important we also perform a validation study in a primary care setting where prevalence of RA would more closely approximate that observed in the general population. The algorithm of [1 hospitalization RA code] OR [3 physician RA diagnosis codes (claims) with ≥1 by a specialist in a 2 year period)] demonstrated a high degree of accuracy in terms of minimizing both the number of false positives (moderately good PPV; 78%) and true negatives (high specificity: 100%). Moreover, this algorithm has excellent sensitivity at capturing contemporary RA patients under active rheumatology care (>96%). Application of this algorithm to Ontario health administrative data to establish the Ontario RA administrative Database (ORAD) identified 97,499 Ontarians with RA as of 2010, yielding a cumulative prevalence of (0.9%). Age/sex-standardized RA prevalence has doubled from 473 per 100,000 in 1996 to 784 per 100,000 in 2010, with approximately 50 new cases of RA emerging per 100,000 Ontarians each year. Our findings will inform future population-based research and will serve to improve arthritis surveillance activities across Canada and abroad.

Rheumatoid arthritis (RA) is a chronic, destructive, inflammatory arthritis that places significant burden on the individual and society. This thesis represents the most comprehensive effort to date to determine the accuracy of administrative data for detecting RA patients; and describes the development and validation of an administrative data algorithm to establish a province-wide RA database. Beginning with a systematic review to guide the conduct of this research, two independent, multicentre, retrospective chart abstraction studies were performed amongst two random samples of patients from rheumatology and primary care family physician practices, respectively. While a diagnosis by a rheumatologist remains the gold standard for establishing a RA diagnosis, the high prevalence of RA in rheumatology clinics can falsely elevate positive predictive values. It was therefore important we also perform a validation study in a primary care setting where prevalence of RA would more closely approximate that observed in the general population. The algorithm of [1 hospitalization RA code] OR [3 physician RA diagnosis codes (claims) with ≥1 by a specialist in a 2 year period)] demonstrated a high degree of accuracy in terms of minimizing both the number of false positives (moderately good PPV; 78%) and true negatives (high specificity: 100%). Moreover, this algorithm has excellent sensitivity at capturing contemporary RA patients under active rheumatology care (>96%). Application of this algorithm to Ontario health administrative data to establish the Ontario RA administrative Database (ORAD) identified 97,499 Ontarians with RA as of 2010, yielding a cumulative prevalence of (0.9%). Age/sex-standardized RA prevalence has doubled from 473 per 100,000 in 1996 to 784 per 100,000 in 2010, with approximately 50 new cases of RA emerging per 100,000 Ontarians each year. Our findings will inform future population-based research and will serve to improve arthritis surveillance activities across Canada and abroad.

No description available.

The goal of this thesis was to examine the processing of clinical pain in two patient groups with well defined primary pathologies, i.e. neuropathic pain patients and patients with rheumatoid arthritis (RA). It was hypothesized that chronic pain is associated with plastic changes in pain processing brain structures that can be detected using functional magnetic resonance imaging (FMRI). The first study, presented in Chapter 3, demonstrates that the neural representation of experimental heat pain is different in neuropathic pain patients than in age- and gender-matched healthy control subjects, although the pain stimulus was applied outside clinically affected areas. Increased activation was found in amygdala and anterior insula in the patient group and was accompanied by increased state anxiety and depression scores. Anterior insula is the focus of Chapter 4 in which it is demonstrated that clinical pain processing is located significantly more anteriorly in the insula than experimental pain processing, in close proximity to neural correlates of highly negative emotions and the conscious perception of bodily sensations. This offers a potential explanation for the shift of clinical pain processing. In Chapter 5, clinical pain is contrasted with experimental pain in the same patient population, i.e. patients with RA. In addition to comparing clinical and experimental pain processing, it was investigated if emotional and cognitive determinates of the pain experience, specifically depression and catastrophizing, exert different influences on the two types of pain. It is shown that clinical pain, but not experimental pain, is likely to be driven partially by depressive symptoms whereas catastrophizing is associated with the same neural activation pattern in both conditions. The cerebral representation of allodynic pain in neuropathic pain patients is presented Chapter 6. Chapters 6 and 7 demonstrate that the FMRI signal encodes the perceived intensity of clinical allodynic pain across subjects and that it reflects longitudinal variations of the perceived intensity within subjects. This thesis illustrates that FMRI can reveal subtle differences in the processing of clinical and experimental pain, despite brain activation patterns being similar on the whole. It also indicates that FMRI can be used to elucidate the origin of these differences, for instance by studying the influence of emotional and cognitive variables. This suggests that neuroimaging methods, in particular FMRI, have the potential to dissect clinical pain into its constituent parts, including central sensitization, brainstem facilitation and amplification by psychological factors. Such knowledge could potentially be exploited to target treatment selectively at different components of clinical pain and to monitor longitudinal changes of these components separately.

Rheumatoid Arthritis (RA) is an autoimmune disease characterized by inflammation and eventual destruction of the synovial joints. The role of platelets in the pathophysiology of arthritis has only recently been established. Because antibodies to CD44 can deplete platelets, we hypothesized that these antibodies might be effective in arthritis through a platelet-depletion mechanism. We examined the K/BxN passive transfer mouse model of arthritis and found that most antibodies against CD44 were capable of depleting platelets. However, anti-CD44 treatment is effective when administered during developing arthritis, while anti-platelet treatment was not. While CD44 antibodies may be therapeutic through platelet-dependant and independent mechanisms, the ability of CD44 antibodies to decrease platelet counts does not seem to be the critical factor in resolving arthritis in the K/BxN model.