Karim Raza - Academia.edu (original) (raw)

Papers by Karim Raza

Research paper thumbnail of 1,25(OH)2D3 Promotes the Efficacy of CD28 Costimulation Blockade by Abatacept

The Journal of Immunology, 2015

The online version of this article contains supplemental material.

Research paper thumbnail of Release of active peptidyl arginine deiminases by neutrophils can explain production of extracellular citrullinated autoantigens in RA synovial fluid

Arthritis & Rheumatology, 2015

Objective: In the majority of patients with rheumatoid arthritis (RA), antibodies specifically re... more Objective: In the majority of patients with rheumatoid arthritis (RA), antibodies specifically recognize citrullinated autoantigens that are generated by peptidylarginine deiminases (PAD).

Research paper thumbnail of Identification of novel antiacetylated vimentin antibodies in patients with early inflammatory arthritis

Annals of the rheumatic diseases, Jan 9, 2015

To investigate serum antibody reactivity against a panel of post-translationally modified vimenti... more To investigate serum antibody reactivity against a panel of post-translationally modified vimentin peptides (PTMPs) in patients with early inflammatory arthritis. A panel of PTMPs was developed. Microtitre plates were coated with peptides derived from vimentin that were identical in length and composition except at one amino acid that was changed to introduce one of three post-translational modifications (PTMs)-either a citrullinated, carbamylated or acetylated residue. Sera of 268 treatment-naive patients with early inflammatory arthritis and symptoms ≤3 months' duration were tested. Patients were assigned to one of three outcome categories at 18-month follow-up (rheumatoid arthritis (RA), persistent non-RA arthritis and resolving arthritis). Antibodies against citrullinated, carbamylated and acetylated vimentin peptides were detected in the sera of patients with early inflammatory arthritis. The proportion of patients seropositive for all antibody types was significantly highe...

Research paper thumbnail of Differential glucocorticoid metabolism in patients with persistent versus resolving inflammatory arthritis

Arthritis research & therapy, 2015

Impairment in the ability of the inflamed synovium to generate cortisol has been proposed to be a... more Impairment in the ability of the inflamed synovium to generate cortisol has been proposed to be a factor in the persistence and severity of inflammatory arthritis. In the inflamed synovium, cortisol is generated from cortisone by the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme. The objective of this study was to determine the role of endogenous glucocorticoid metabolism in the development of persistent inflammatory arthritis. Urine samples were collected from patients with early arthritis (symptoms ≤12 weeks duration) whose final diagnostic outcomes were established after clinical follow-up and from patients with established rheumatoid arthritis (RA). All patients were free of disease-modifying anti-rheumatic drugs at the time of sample collection. Systemic measures of glucocorticoid metabolism were assessed in the urine samples by gas chromatography/mass spectrometry. Clinical data including CRP and ESR were also collected at baseline. Systemic measures of 11β-HSD1 ac...

Research paper thumbnail of Homeostatic regulation of T cell trafficking by a B cell-derived peptide is impaired in autoimmune and chronic inflammatory disease

Nature medicine, Jan 20, 2015

During an inflammatory response, lymphocyte recruitment into tissue must be tightly controlled be... more During an inflammatory response, lymphocyte recruitment into tissue must be tightly controlled because dysregulated trafficking contributes to the pathogenesis of chronic disease. Here we show that during inflammation and in response to adiponectin, B cells tonically inhibit T cell trafficking by secreting a peptide (PEPITEM) proteolytically derived from 14.3.3 zeta delta (14.3.3.ζδ) protein. PEPITEM binds cadherin-15 on endothelial cells, promoting synthesis and release of sphingosine-1 phosphate, which inhibits trafficking of T cells without affecting recruitment of other leukocytes. Expression of adiponectin receptors on B cells and adiponectin-induced PEPITEM secretion wanes with age, implying immune senescence of the pathway. Additionally, these changes are evident in individuals with type 1 diabetes or rheumatoid arthritis, and circulating PEPITEM in patient serum is reduced compared to that of healthy age-matched donors. In both diseases, tonic inhibition of T cell traffickin...

Research paper thumbnail of Stromal transcriptional profiles reveal hierarchies of anatomical site, serum response and disease and identify disease specific pathways

PloS one, 2015

Synovial fibroblasts in persistent inflammatory arthritis have been suggested to have parallels w... more Synovial fibroblasts in persistent inflammatory arthritis have been suggested to have parallels with cancer growth and wound healing, both of which involve a stereotypical serum response programme. We tested the hypothesis that a serum response programme can be used to classify diseased tissues, and investigated the serum response programme in fibroblasts from multiple anatomical sites and two diseases. To test our hypothesis we utilized a bioinformatics approach to explore a publicly available microarray dataset including rheumatoid arthritis (RA), osteoarthritis (OA) and normal synovial tissue, then extended those findings in a new microarray dataset representing matched synovial, bone marrow and skin fibroblasts cultured from RA and OA patients undergoing arthroplasty. The classical fibroblast serum response programme discretely classified RA, OA and normal synovial tissues. Analysis of low and high serum treated fibroblast microarray data revealed a hierarchy of control, with an...

Research paper thumbnail of Biomarkers of early stage osteoarthritis, rheumatoid arthritis and musculoskeletal health

Research paper thumbnail of Reversing myocardial microvascular disease in a patient with rheumatoid arthritis

The Journal of rheumatology, 2005

Rheumatoid arthritis (RA) is associated with increased cardiovascular mortality. This is regarded... more Rheumatoid arthritis (RA) is associated with increased cardiovascular mortality. This is regarded as being due to accelerated coronary atherosclerosis. We describe a 62-year-old man with seropositive erosive RA and extraarticular manifestations but no history of cardiovascular disease. Noninvasive assessment of myocardial blood flow by adenosine stressed thallium scanning showed reversible ischemia and diffusely poor myocardial perfusion. Repeat assessment after intensive immunosuppression for rheumatoid vasculitis revealed resolution of the ischemic changes and generally increased myocardial perfusion. Coronary angiography revealed no significant atheroma, suggesting that myocardial microvascular disease was responsible for the ischemia. This may be an important determinant of cardiovascular outcome in RA, and this case indicated that it can be reversed with immunosuppression.

Research paper thumbnail of Dramatic aneurysm regression in polyarteritis nodosa following high dose pulse cyclophosphamide

The Journal of rheumatology, 2000

Research paper thumbnail of A Qualitative Investigation of the Barriers to Help-seeking Among Members of the Public Presented with Symptoms of New-onset Rheumatoid Arthritis

The Journal of rheumatology, 2015

Treating patients with rheumatoid arthritis (RA) within 3 months of symptom onset leads to signif... more Treating patients with rheumatoid arthritis (RA) within 3 months of symptom onset leads to significantly improved clinical outcomes. However, many people with RA symptoms wait a long time before seeking medical attention. To develop effective health interventions to encourage people to seek help early, it is important to understand what the general public knows about RA, how they would react to the symptoms of RA, and what might delay help-seeking. Qualitative interviews were conducted with 38 members of the general public (32 women) without any form of inflammatory arthritis about their perceptions of RA symptoms and decisions to seek help were they to experience such symptoms. The interviews were audio-recorded, transcribed verbatim, and analyzed using thematic analysis. A number of barriers and drivers to help-seeking were identified and grouped into 5 themes: perceived causes of symptoms; factors related to presentation, location, and experience of symptoms; perceived effect of ...

Research paper thumbnail of The development and initial validation of a questionnaire to measure help-seeking behaviour in patients with new onset rheumatoid arthritis

Health expectations : an international journal of public participation in health care and health policy, Jan 3, 2014

Early treatment for rheumatoid arthritis (RA) is vital. However, people often delay in seeking he... more Early treatment for rheumatoid arthritis (RA) is vital. However, people often delay in seeking help at symptom onset. An assessment of the reasons behind patient delay is necessary to develop interventions to promote rapid consultation. Using a mixed methods design, we aimed to develop and test a questionnaire to assess the barriers to help seeking at RA onset. Questionnaire items were extracted from previous qualitative studies. Fifteen people with a lived experience of arthritis participated in focus groups to enhance the questionnaire's face validity. The questionnaire was also reviewed by groups of multidisciplinary health-care professionals. A test-retest survey of 41 patients with newly presenting RA or unclassified arthritis assessed the questionnaire items' intraclass correlations. During focus groups, participants rephrased questions, added questions and deleted items not relevant to the questionnaire's aims. Participants organized items into themes: early sympt...

Research paper thumbnail of The assessment of T-cell apoptosis in synovial fluid

Methods in molecular medicine, 2007

T-cell apoptosis is central to the resolution of chronic inflammation. Inhibition of this process... more T-cell apoptosis is central to the resolution of chronic inflammation. Inhibition of this process of programmed cell death contributes to disease persistence in conditions such as rheumatoid arthritis. An understanding of T-cell apoptosis and its regulation is clearly important for understanding the pathophysiology of inflammatory disease. This chapter describes a number of apoptosis assays that can be used to measure T-cell apoptosis in synovial fluid. The choice of assay depends, in part, on the phase of apoptosis under investigation and this review puts this into context by introducing these phases and their regulation.

Research paper thumbnail of Exploring the cultural validity of rheumatology outcomes

British Journal of Nursing, 2012

In rheumatoid arthritis (RA), the use of a &a... more In rheumatoid arthritis (RA), the use of a 'core' set of treatment outcomes was pioneered to ensure that the same outcomes are measured across all clinical trials to enable comparison of trial results. However, studies have not investigated the influence of patients' ethnic and cultural backgrounds on treatment outcomes. This pilot study identified 74 treatment outcomes from female Punjabi RA patients, including 21 new ones that were not identified in previous research with white British RA patients. The social impact of RA created significant additional burden for these Punjabi women, with 'less stigmatisation' and 'improved ability to carry out family duties' generated as important new outcomes. This study illustrates a need to address cultural validity in outcome elicitation and prioritisation, to ensure that interventions are evaluated using criteria that have meaning for people with that condition.

Research paper thumbnail of Symptom complexes in patients with seropositive arthralgia and in patients newly diagnosed with rheumatoid arthritis: a qualitative exploration of symptom development

Rheumatology, 2014

The aim of this study was to explore symptoms and symptom development during the earliest phases ... more The aim of this study was to explore symptoms and symptom development during the earliest phases of RA in patients with seropositive arthralgia and patients newly diagnosed with RA. Interviews were conducted with 15 seropositive patients (anti-CCP positive, and often with arthralgia) and 11 newly presenting RA patients [classified according to the 2010 ACR/European League Against Rheumatism (EULAR) criteria]. Feedback procedures shared the experiences of seropositive arthralgia patients with early RA patients and vice versa. Data were analysed using thematic analysis. Symptoms common to both groups included joint pain, psychological distress, muscle cramps, abnormal skin sensations, stiffness, loss of motor control, weakness, fatigue and sleeping difficulties. Also, patterns of symptom evolution and the order of symptom development were described. Seropositive arthralgia patients described pain as annoying, while RA patients described how the severity of pain intensified before diagnosis, to the point where symptoms were psychologically distressing. Patients with seropositive arthralgia described reddening of the skin and burning sensations that they felt were indicative of the onset of swelling. Intense pain appeared to precede the onset of swelling for those with RA, which was often palindromic and travelled between joints until it later became persistent. This study highlights the breadth of symptoms that constitute the earliest phases of RA. Further research is needed to develop measures of symptom patterns and clusters to allow the predictive utility of symptoms to be assessed and to allow the integration of aspects of the patient's history into evidence-based investigative and management algorithms for use in primary and secondary care.

Research paper thumbnail of Experience with a Punjabi, Urdu and Hindi rheumatology telephone helpline

Musculoskeletal Care, 2009

To investigate what proportion of patients attending a rheumatology unit in Birmingham, UK, requi... more To investigate what proportion of patients attending a rheumatology unit in Birmingham, UK, require interpretation services and to assess the use of an Asian language telephone helpline we have established for those who find it easier to communicate in Punjabi, Urdu or Hindi than in English. Our patients' requirement for interpretation services and their ability to read the script of the language they preferred to communicate in was assessed. A second survey assessed the use of an Asian language helpline we had established. All calls were recorded over 18 months. The reasons for the calls were categorized and compared with those made to our English helpline. 171 of 512 patients (33%) stated that they required interpretation services. 128 (25%) were not able to read the script of their preferred language. In the second survey, 101 calls to the Asian language helpline were assessed and were compared with calls to the English helpline. The reasons for the calls differed between the helplines. A large proportion of patients attending our rheumatology unit required interpretation services to communicate effectively with their healthcare professional. Most of these patients were unable to read the script of the language they could speak, casting some doubt over the utility of translated written information. Patients of South Asian origin who preferred to communicate in Punjabi, Urdu or Hindi made use of a helpline operating in these languages, suggesting that this may be an effective strategy to facilitate communication with this group of patients.

Research paper thumbnail of THE ROLE OF ENDOTHELIAL CELL DYSFUNCTION IN THE CARDIOVASCULAR MORTALITY OF RA

International Reviews of Immunology, 2002

Rheumatoid patients present clinically with chronic inflammatory immune arthritis but die of the ... more Rheumatoid patients present clinically with chronic inflammatory immune arthritis but die of the same cardiovascular (CVS) disease as the normal population. Recent studies emphasize the increased frequency and earlier development of CVS involvement in RA. The mechanisms of this accelerated atherosclerosis are the subject of active research. The hypothesis that rheumatoid vasculitis is a major factor has been pursued through studies in primary systemic vasculitis. These reveal diffuse endothelial dysfunction occurring across a spectrum of vasculitis and involving more than one vascular bed. This may relate to cytokines such as TNF alpha that are both prominent in rheumatoid inflammation and important in the upregulation of endothelium in innate immune responses. Endothelial injury or dysfunction is widely accepted as the initial factor in atheroma. Its occurrence in vasculitis leads us to propose a model for RA where this dysfunction is the essential first step on which other factors, ranging from adverse lipid profiles to specific T-cell subsets, may build accelerated atherogenesis related to the rheumatoid inflammation.

Research paper thumbnail of Suppression of Inflammation in Primary Systemic Vasculitis Restores Vascular Endothelial Function: Lessons for Atherosclerotic Disease?

Circulation, 2000

Background-Chronic inflammatory rheumatic disorders are associated with excess cardiovascular mor... more Background-Chronic inflammatory rheumatic disorders are associated with excess cardiovascular mortality. This may result from arteriosclerosis following inflammatory damage to the vessel wall by vasculitis. Our hypothesis that vasculitis results in arteriosclerosis by causing vascular endothelial dysfunction was tested in patients with primary systemic necrotizing vasculitis (SNV).

Research paper thumbnail of The relationship between the presence of anti-cyclic citrullinated peptide antibodies and clinical phenotype in very early rheumatoid arthritis

BMC Musculoskeletal Disorders, 2010

Background: Anti-cyclic citrullinated peptide (anti-CCP) antibodies are highly specific for RA, b... more Background: Anti-cyclic citrullinated peptide (anti-CCP) antibodies are highly specific for RA, but are not detectable in all RA patients. The aim of this study was to establish whether the clinical phenotypes of anti-CCP positive and negative disease are distinct at the earliest clinically apparent phase of disease. Methods: Patients were recruited from the Birmingham early inflammatory arthritis clinic. Participants were included in the current study if they presented within 3 months of symptom onset and fulfilled 1987 ACR criteria for RA at some point during an 18 month follow-up. Data were collected on demographic variables, joint symptoms and tender (n = 68) and swollen (n = 66) joint counts. CRP, ESR, rheumatoid factor and anti-CCP2 status were measured. Results: 92 patients were included (48 anti-CCP positive). The anti-CCP positive and negative groups were comparable in terms of demographic variables, inflammatory markers, joint counts and 1987 ACR classification criteria, except that more anti-CCP positive patients were rheumatoid factor positive (83.3% vs. 11.4%, p < 0.01). There was no significant difference in the pattern of joint involvement, except for an increased prevalence of knee joint swelling in anti-CCP positive patients (42.9% vs. 22.2%, p = 0.03). Conclusions: Patients with and without anti-CCP antibodies present in a similar way, even within three months of clinically apparent disease that eventually develops into RA.

Research paper thumbnail of Validation of a prediction rule for disease outcome in patients with recent-onset undifferentiated arthritis: Moving toward individualized treatment decision-making

Arthritis & Rheumatism, 2008

Objective. The decision to start disease-modifying antirheumatic drugs in patients with recent-on... more Objective. The decision to start disease-modifying antirheumatic drugs in patients with recent-onset undifferentiated arthritis (UA) is complicated by a varied natural disease course in which the disease in one-third of patients progresses to rheumatoid arthritis (RA), whereas 40-50% of patients experience spontaneous remission. Recently, a prediction rule was developed to estimate the chance of progression to RA in individual patients presenting with UA. This study investigates the accuracy of this prediction rule in independent cohorts of patients with UA.

Research paper thumbnail of Association of circulating miR-223 and miR-16 with disease activity in patients with early rheumatoid arthritis

Annals of the Rheumatic Diseases, 2013

Identification of parameters for early diagnosis and treatment response would be beneficial for p... more Identification of parameters for early diagnosis and treatment response would be beneficial for patients with early rheumatoid arthritis (ERA) to prevent ongoing joint damage. miRNAs have features of potential biomarkers, and an altered expression of miRNAs was shown in established rheumatoid arthritis (RA). To analyse RA associated miRNAs in the sera of patients with ERA to find markers of early disease, clinical activity or predictors of disease outcome. Total RNA was isolated from whole sera in ERA patients (prior to and after 3 and 12 months of therapy with disease modifying antirheumatic drugs), in patients with established RA and in healthy controls (HC) using phenol-chloroform extraction. Expression of miR-146a, miR-155, miR-223, miR-16, miR-203, miR-132 and miR-124a was analysed by TaqMan Real Time PCR. From all analysed miRNAs, levels of miR-146a, miR-155 and miR-16 were decreased in the sera of ERA patients in comparison with established RA. A change in circulating miR-16 in the first 3 months of therapy was associated with a decrease in DAS28 in long term follow-up in ERA (p=0.002). Levels of circulating miR-223 in treatment naïve ERA correlated with C reactive protein (p=0.008), DAS28 (p=0.031) and change in DAS28 after 3 months (p=0.003) and 12 months (p=0.011) of follow-up. However, neither miR-16 nor miR-223 could distinguish ERA from HC. Differential expression of circulating miR-146a, miR-155 and miR-16 in the sera of ERA patients may characterise an early stage of the disease. We suggest miR-223 as a marker of disease activity and miR-16 and miR-223 as possible predictors for disease outcome in ERA.

Research paper thumbnail of 1,25(OH)2D3 Promotes the Efficacy of CD28 Costimulation Blockade by Abatacept

The Journal of Immunology, 2015

The online version of this article contains supplemental material.

Research paper thumbnail of Release of active peptidyl arginine deiminases by neutrophils can explain production of extracellular citrullinated autoantigens in RA synovial fluid

Arthritis & Rheumatology, 2015

Objective: In the majority of patients with rheumatoid arthritis (RA), antibodies specifically re... more Objective: In the majority of patients with rheumatoid arthritis (RA), antibodies specifically recognize citrullinated autoantigens that are generated by peptidylarginine deiminases (PAD).

Research paper thumbnail of Identification of novel antiacetylated vimentin antibodies in patients with early inflammatory arthritis

Annals of the rheumatic diseases, Jan 9, 2015

To investigate serum antibody reactivity against a panel of post-translationally modified vimenti... more To investigate serum antibody reactivity against a panel of post-translationally modified vimentin peptides (PTMPs) in patients with early inflammatory arthritis. A panel of PTMPs was developed. Microtitre plates were coated with peptides derived from vimentin that were identical in length and composition except at one amino acid that was changed to introduce one of three post-translational modifications (PTMs)-either a citrullinated, carbamylated or acetylated residue. Sera of 268 treatment-naive patients with early inflammatory arthritis and symptoms ≤3 months' duration were tested. Patients were assigned to one of three outcome categories at 18-month follow-up (rheumatoid arthritis (RA), persistent non-RA arthritis and resolving arthritis). Antibodies against citrullinated, carbamylated and acetylated vimentin peptides were detected in the sera of patients with early inflammatory arthritis. The proportion of patients seropositive for all antibody types was significantly highe...

Research paper thumbnail of Differential glucocorticoid metabolism in patients with persistent versus resolving inflammatory arthritis

Arthritis research & therapy, 2015

Impairment in the ability of the inflamed synovium to generate cortisol has been proposed to be a... more Impairment in the ability of the inflamed synovium to generate cortisol has been proposed to be a factor in the persistence and severity of inflammatory arthritis. In the inflamed synovium, cortisol is generated from cortisone by the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme. The objective of this study was to determine the role of endogenous glucocorticoid metabolism in the development of persistent inflammatory arthritis. Urine samples were collected from patients with early arthritis (symptoms ≤12 weeks duration) whose final diagnostic outcomes were established after clinical follow-up and from patients with established rheumatoid arthritis (RA). All patients were free of disease-modifying anti-rheumatic drugs at the time of sample collection. Systemic measures of glucocorticoid metabolism were assessed in the urine samples by gas chromatography/mass spectrometry. Clinical data including CRP and ESR were also collected at baseline. Systemic measures of 11β-HSD1 ac...

Research paper thumbnail of Homeostatic regulation of T cell trafficking by a B cell-derived peptide is impaired in autoimmune and chronic inflammatory disease

Nature medicine, Jan 20, 2015

During an inflammatory response, lymphocyte recruitment into tissue must be tightly controlled be... more During an inflammatory response, lymphocyte recruitment into tissue must be tightly controlled because dysregulated trafficking contributes to the pathogenesis of chronic disease. Here we show that during inflammation and in response to adiponectin, B cells tonically inhibit T cell trafficking by secreting a peptide (PEPITEM) proteolytically derived from 14.3.3 zeta delta (14.3.3.ζδ) protein. PEPITEM binds cadherin-15 on endothelial cells, promoting synthesis and release of sphingosine-1 phosphate, which inhibits trafficking of T cells without affecting recruitment of other leukocytes. Expression of adiponectin receptors on B cells and adiponectin-induced PEPITEM secretion wanes with age, implying immune senescence of the pathway. Additionally, these changes are evident in individuals with type 1 diabetes or rheumatoid arthritis, and circulating PEPITEM in patient serum is reduced compared to that of healthy age-matched donors. In both diseases, tonic inhibition of T cell traffickin...

Research paper thumbnail of Stromal transcriptional profiles reveal hierarchies of anatomical site, serum response and disease and identify disease specific pathways

PloS one, 2015

Synovial fibroblasts in persistent inflammatory arthritis have been suggested to have parallels w... more Synovial fibroblasts in persistent inflammatory arthritis have been suggested to have parallels with cancer growth and wound healing, both of which involve a stereotypical serum response programme. We tested the hypothesis that a serum response programme can be used to classify diseased tissues, and investigated the serum response programme in fibroblasts from multiple anatomical sites and two diseases. To test our hypothesis we utilized a bioinformatics approach to explore a publicly available microarray dataset including rheumatoid arthritis (RA), osteoarthritis (OA) and normal synovial tissue, then extended those findings in a new microarray dataset representing matched synovial, bone marrow and skin fibroblasts cultured from RA and OA patients undergoing arthroplasty. The classical fibroblast serum response programme discretely classified RA, OA and normal synovial tissues. Analysis of low and high serum treated fibroblast microarray data revealed a hierarchy of control, with an...

Research paper thumbnail of Biomarkers of early stage osteoarthritis, rheumatoid arthritis and musculoskeletal health

Research paper thumbnail of Reversing myocardial microvascular disease in a patient with rheumatoid arthritis

The Journal of rheumatology, 2005

Rheumatoid arthritis (RA) is associated with increased cardiovascular mortality. This is regarded... more Rheumatoid arthritis (RA) is associated with increased cardiovascular mortality. This is regarded as being due to accelerated coronary atherosclerosis. We describe a 62-year-old man with seropositive erosive RA and extraarticular manifestations but no history of cardiovascular disease. Noninvasive assessment of myocardial blood flow by adenosine stressed thallium scanning showed reversible ischemia and diffusely poor myocardial perfusion. Repeat assessment after intensive immunosuppression for rheumatoid vasculitis revealed resolution of the ischemic changes and generally increased myocardial perfusion. Coronary angiography revealed no significant atheroma, suggesting that myocardial microvascular disease was responsible for the ischemia. This may be an important determinant of cardiovascular outcome in RA, and this case indicated that it can be reversed with immunosuppression.

Research paper thumbnail of Dramatic aneurysm regression in polyarteritis nodosa following high dose pulse cyclophosphamide

The Journal of rheumatology, 2000

Research paper thumbnail of A Qualitative Investigation of the Barriers to Help-seeking Among Members of the Public Presented with Symptoms of New-onset Rheumatoid Arthritis

The Journal of rheumatology, 2015

Treating patients with rheumatoid arthritis (RA) within 3 months of symptom onset leads to signif... more Treating patients with rheumatoid arthritis (RA) within 3 months of symptom onset leads to significantly improved clinical outcomes. However, many people with RA symptoms wait a long time before seeking medical attention. To develop effective health interventions to encourage people to seek help early, it is important to understand what the general public knows about RA, how they would react to the symptoms of RA, and what might delay help-seeking. Qualitative interviews were conducted with 38 members of the general public (32 women) without any form of inflammatory arthritis about their perceptions of RA symptoms and decisions to seek help were they to experience such symptoms. The interviews were audio-recorded, transcribed verbatim, and analyzed using thematic analysis. A number of barriers and drivers to help-seeking were identified and grouped into 5 themes: perceived causes of symptoms; factors related to presentation, location, and experience of symptoms; perceived effect of ...

Research paper thumbnail of The development and initial validation of a questionnaire to measure help-seeking behaviour in patients with new onset rheumatoid arthritis

Health expectations : an international journal of public participation in health care and health policy, Jan 3, 2014

Early treatment for rheumatoid arthritis (RA) is vital. However, people often delay in seeking he... more Early treatment for rheumatoid arthritis (RA) is vital. However, people often delay in seeking help at symptom onset. An assessment of the reasons behind patient delay is necessary to develop interventions to promote rapid consultation. Using a mixed methods design, we aimed to develop and test a questionnaire to assess the barriers to help seeking at RA onset. Questionnaire items were extracted from previous qualitative studies. Fifteen people with a lived experience of arthritis participated in focus groups to enhance the questionnaire's face validity. The questionnaire was also reviewed by groups of multidisciplinary health-care professionals. A test-retest survey of 41 patients with newly presenting RA or unclassified arthritis assessed the questionnaire items' intraclass correlations. During focus groups, participants rephrased questions, added questions and deleted items not relevant to the questionnaire's aims. Participants organized items into themes: early sympt...

Research paper thumbnail of The assessment of T-cell apoptosis in synovial fluid

Methods in molecular medicine, 2007

T-cell apoptosis is central to the resolution of chronic inflammation. Inhibition of this process... more T-cell apoptosis is central to the resolution of chronic inflammation. Inhibition of this process of programmed cell death contributes to disease persistence in conditions such as rheumatoid arthritis. An understanding of T-cell apoptosis and its regulation is clearly important for understanding the pathophysiology of inflammatory disease. This chapter describes a number of apoptosis assays that can be used to measure T-cell apoptosis in synovial fluid. The choice of assay depends, in part, on the phase of apoptosis under investigation and this review puts this into context by introducing these phases and their regulation.

Research paper thumbnail of Exploring the cultural validity of rheumatology outcomes

British Journal of Nursing, 2012

In rheumatoid arthritis (RA), the use of a &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;a... more In rheumatoid arthritis (RA), the use of a &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;core&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; set of treatment outcomes was pioneered to ensure that the same outcomes are measured across all clinical trials to enable comparison of trial results. However, studies have not investigated the influence of patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; ethnic and cultural backgrounds on treatment outcomes. This pilot study identified 74 treatment outcomes from female Punjabi RA patients, including 21 new ones that were not identified in previous research with white British RA patients. The social impact of RA created significant additional burden for these Punjabi women, with &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;less stigmatisation&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; and &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;improved ability to carry out family duties&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; generated as important new outcomes. This study illustrates a need to address cultural validity in outcome elicitation and prioritisation, to ensure that interventions are evaluated using criteria that have meaning for people with that condition.

Research paper thumbnail of Symptom complexes in patients with seropositive arthralgia and in patients newly diagnosed with rheumatoid arthritis: a qualitative exploration of symptom development

Rheumatology, 2014

The aim of this study was to explore symptoms and symptom development during the earliest phases ... more The aim of this study was to explore symptoms and symptom development during the earliest phases of RA in patients with seropositive arthralgia and patients newly diagnosed with RA. Interviews were conducted with 15 seropositive patients (anti-CCP positive, and often with arthralgia) and 11 newly presenting RA patients [classified according to the 2010 ACR/European League Against Rheumatism (EULAR) criteria]. Feedback procedures shared the experiences of seropositive arthralgia patients with early RA patients and vice versa. Data were analysed using thematic analysis. Symptoms common to both groups included joint pain, psychological distress, muscle cramps, abnormal skin sensations, stiffness, loss of motor control, weakness, fatigue and sleeping difficulties. Also, patterns of symptom evolution and the order of symptom development were described. Seropositive arthralgia patients described pain as annoying, while RA patients described how the severity of pain intensified before diagnosis, to the point where symptoms were psychologically distressing. Patients with seropositive arthralgia described reddening of the skin and burning sensations that they felt were indicative of the onset of swelling. Intense pain appeared to precede the onset of swelling for those with RA, which was often palindromic and travelled between joints until it later became persistent. This study highlights the breadth of symptoms that constitute the earliest phases of RA. Further research is needed to develop measures of symptom patterns and clusters to allow the predictive utility of symptoms to be assessed and to allow the integration of aspects of the patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s history into evidence-based investigative and management algorithms for use in primary and secondary care.

Research paper thumbnail of Experience with a Punjabi, Urdu and Hindi rheumatology telephone helpline

Musculoskeletal Care, 2009

To investigate what proportion of patients attending a rheumatology unit in Birmingham, UK, requi... more To investigate what proportion of patients attending a rheumatology unit in Birmingham, UK, require interpretation services and to assess the use of an Asian language telephone helpline we have established for those who find it easier to communicate in Punjabi, Urdu or Hindi than in English. Our patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; requirement for interpretation services and their ability to read the script of the language they preferred to communicate in was assessed. A second survey assessed the use of an Asian language helpline we had established. All calls were recorded over 18 months. The reasons for the calls were categorized and compared with those made to our English helpline. 171 of 512 patients (33%) stated that they required interpretation services. 128 (25%) were not able to read the script of their preferred language. In the second survey, 101 calls to the Asian language helpline were assessed and were compared with calls to the English helpline. The reasons for the calls differed between the helplines. A large proportion of patients attending our rheumatology unit required interpretation services to communicate effectively with their healthcare professional. Most of these patients were unable to read the script of the language they could speak, casting some doubt over the utility of translated written information. Patients of South Asian origin who preferred to communicate in Punjabi, Urdu or Hindi made use of a helpline operating in these languages, suggesting that this may be an effective strategy to facilitate communication with this group of patients.

Research paper thumbnail of THE ROLE OF ENDOTHELIAL CELL DYSFUNCTION IN THE CARDIOVASCULAR MORTALITY OF RA

International Reviews of Immunology, 2002

Rheumatoid patients present clinically with chronic inflammatory immune arthritis but die of the ... more Rheumatoid patients present clinically with chronic inflammatory immune arthritis but die of the same cardiovascular (CVS) disease as the normal population. Recent studies emphasize the increased frequency and earlier development of CVS involvement in RA. The mechanisms of this accelerated atherosclerosis are the subject of active research. The hypothesis that rheumatoid vasculitis is a major factor has been pursued through studies in primary systemic vasculitis. These reveal diffuse endothelial dysfunction occurring across a spectrum of vasculitis and involving more than one vascular bed. This may relate to cytokines such as TNF alpha that are both prominent in rheumatoid inflammation and important in the upregulation of endothelium in innate immune responses. Endothelial injury or dysfunction is widely accepted as the initial factor in atheroma. Its occurrence in vasculitis leads us to propose a model for RA where this dysfunction is the essential first step on which other factors, ranging from adverse lipid profiles to specific T-cell subsets, may build accelerated atherogenesis related to the rheumatoid inflammation.

Research paper thumbnail of Suppression of Inflammation in Primary Systemic Vasculitis Restores Vascular Endothelial Function: Lessons for Atherosclerotic Disease?

Circulation, 2000

Background-Chronic inflammatory rheumatic disorders are associated with excess cardiovascular mor... more Background-Chronic inflammatory rheumatic disorders are associated with excess cardiovascular mortality. This may result from arteriosclerosis following inflammatory damage to the vessel wall by vasculitis. Our hypothesis that vasculitis results in arteriosclerosis by causing vascular endothelial dysfunction was tested in patients with primary systemic necrotizing vasculitis (SNV).

Research paper thumbnail of The relationship between the presence of anti-cyclic citrullinated peptide antibodies and clinical phenotype in very early rheumatoid arthritis

BMC Musculoskeletal Disorders, 2010

Background: Anti-cyclic citrullinated peptide (anti-CCP) antibodies are highly specific for RA, b... more Background: Anti-cyclic citrullinated peptide (anti-CCP) antibodies are highly specific for RA, but are not detectable in all RA patients. The aim of this study was to establish whether the clinical phenotypes of anti-CCP positive and negative disease are distinct at the earliest clinically apparent phase of disease. Methods: Patients were recruited from the Birmingham early inflammatory arthritis clinic. Participants were included in the current study if they presented within 3 months of symptom onset and fulfilled 1987 ACR criteria for RA at some point during an 18 month follow-up. Data were collected on demographic variables, joint symptoms and tender (n = 68) and swollen (n = 66) joint counts. CRP, ESR, rheumatoid factor and anti-CCP2 status were measured. Results: 92 patients were included (48 anti-CCP positive). The anti-CCP positive and negative groups were comparable in terms of demographic variables, inflammatory markers, joint counts and 1987 ACR classification criteria, except that more anti-CCP positive patients were rheumatoid factor positive (83.3% vs. 11.4%, p < 0.01). There was no significant difference in the pattern of joint involvement, except for an increased prevalence of knee joint swelling in anti-CCP positive patients (42.9% vs. 22.2%, p = 0.03). Conclusions: Patients with and without anti-CCP antibodies present in a similar way, even within three months of clinically apparent disease that eventually develops into RA.

Research paper thumbnail of Validation of a prediction rule for disease outcome in patients with recent-onset undifferentiated arthritis: Moving toward individualized treatment decision-making

Arthritis & Rheumatism, 2008

Objective. The decision to start disease-modifying antirheumatic drugs in patients with recent-on... more Objective. The decision to start disease-modifying antirheumatic drugs in patients with recent-onset undifferentiated arthritis (UA) is complicated by a varied natural disease course in which the disease in one-third of patients progresses to rheumatoid arthritis (RA), whereas 40-50% of patients experience spontaneous remission. Recently, a prediction rule was developed to estimate the chance of progression to RA in individual patients presenting with UA. This study investigates the accuracy of this prediction rule in independent cohorts of patients with UA.

Research paper thumbnail of Association of circulating miR-223 and miR-16 with disease activity in patients with early rheumatoid arthritis

Annals of the Rheumatic Diseases, 2013

Identification of parameters for early diagnosis and treatment response would be beneficial for p... more Identification of parameters for early diagnosis and treatment response would be beneficial for patients with early rheumatoid arthritis (ERA) to prevent ongoing joint damage. miRNAs have features of potential biomarkers, and an altered expression of miRNAs was shown in established rheumatoid arthritis (RA). To analyse RA associated miRNAs in the sera of patients with ERA to find markers of early disease, clinical activity or predictors of disease outcome. Total RNA was isolated from whole sera in ERA patients (prior to and after 3 and 12 months of therapy with disease modifying antirheumatic drugs), in patients with established RA and in healthy controls (HC) using phenol-chloroform extraction. Expression of miR-146a, miR-155, miR-223, miR-16, miR-203, miR-132 and miR-124a was analysed by TaqMan Real Time PCR. From all analysed miRNAs, levels of miR-146a, miR-155 and miR-16 were decreased in the sera of ERA patients in comparison with established RA. A change in circulating miR-16 in the first 3 months of therapy was associated with a decrease in DAS28 in long term follow-up in ERA (p=0.002). Levels of circulating miR-223 in treatment naïve ERA correlated with C reactive protein (p=0.008), DAS28 (p=0.031) and change in DAS28 after 3 months (p=0.003) and 12 months (p=0.011) of follow-up. However, neither miR-16 nor miR-223 could distinguish ERA from HC. Differential expression of circulating miR-146a, miR-155 and miR-16 in the sera of ERA patients may characterise an early stage of the disease. We suggest miR-223 as a marker of disease activity and miR-16 and miR-223 as possible predictors for disease outcome in ERA.