Dissertations / Theses on the topic 'Arthritis Prognosis'

Objectives: to assess the value of quantitative vascular imaging by power Doppler ultrasound (PDUS) as a tool that can be used to stratify patient risk of joint damage in early seropositive RA while still biologic-naive but on synthetic DMARD treatment. Methods: 85 patients with seropositive RA <3 years duration, had clinical, laboratory and imaging assessments at 0, 6 and 12 months. Imaging assessments consisted of radiographs of hands and feet, 2 dimensional high frequency and PDUS imaging of 10 metacarpophalangeal joints (MCPJs) which were scored for erosions and vascularity, and 3 dimensional PDUS of MCPJs and wrists which were scored for vascularity. Results: Severe deterioration on radiographs and ultrasonography was seen in 45% and 28% of patients respectively. 3D PD volume and 2D vascularity scores were the most useful ultrasound predictors of deterioration. These variables were modelled in 2 equations which estimate structural damage over 12 months. The equations had a sensitivity of 63.2% and specificity of 80.9% for predicting structural damage on x-ray, and a sensitivity of 54.2% and specificity of 96.7% for predicting structural damage on ultrasound. Conclusions: In seropositive early RA, quantitative vascular imaging by PDUS has clinical utility in predicting which patients would derive benefit from early use of biologics therapy.

Rheumatoid arthritis (RA) which affects 0.5-1% of the world population and is characterised by joint erosions and presence of the autoantibodies anti-citrullinated protein antibodies (ACPA) and rheumatoid factor. Collagen II (CII) is a joint-specific antigen and we have shown that antibodies against CII (anti-CII) are present in around 8% of RA patients. RA patients with anti-CII are characterized by acute RA onset with elevated CRP and early joint erosions at the time of RA onset. Polymorphonuclear granulocytes (PMN) and peripheral blood mononuclear cells (PBMC) are abundant in RA synovial fluids, where they can interact with anti-CII, thus forming immune complexes (IC) with CII. In my thesis I have shown that PMN upregulated the cell surface markers CD66b and CD11b and downregulated CD16 and CD32 after stimulation with anti-CII IC. These changes in CD66b and CD16 associated to joint erosions to a larger extent than did PBMC responses to anti-CII IC. PMN cocultured with PBMC and stimulated with anti-CII IC showed augmented chemokine production that was dependent on TLR4 and functionally active PMN enzymes. This mechanism can lead to accumulation of inflammatory cells in joints of RA patients who are anti-CII positive around the time of RA diagnosis, and may thus help explain the acute onset RA phenotype associated with anti-CII. In a large Swedish RA cohort, anti-CII associated with elevations in clinical and laboratory measures of disease activity at diagnosis and until 6 months, whereas ACPA associated with late inflammation. Anti-CII seropositive RA was associated with improvements in clinical measurements and was negatively associated with smoking in contrast to ACPA that was associated with worseneing of clinical symptoms and associated positively with smoking. Anti-CII levels associated to  HLADRB1*03 and  HLADRB1*01 whereas ACPA showed negative association to HLA-DRB1*03. In a Malaysian RA cohort anti-CII also associated to elevated CRP at the time of diagnosis. Anti-CII seropositive RA represents a distinct phenotype, in many respects representing the converse  to the clinical, genetic and smoking associations described for ACPA. Early determinations of anti-CII in parallel to ACPA predict the inflammatory outcome in RA.

Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory disease. Treatment strategies emphasize early multi-professional interventions to reduce disease activity and to prevent disability, but there is a lack of knowledge on how optimal treatment can be provided to each individual patient. Aim: To elucidate how clinical manifestations of early RA are associated to disease and disability outcomes, to strive for greater potential to establish prognosis in early RA, and to facilitate implementation of decision support through analyses of the decision-making environment in chronic care. Methods: Multivariate statistics and mathematical modelling, as well as field observations and focus group interviews. Results: Decision support: A prognostic tree that predicted patients with a poor prognosis (moderate or high levels of DAS-28) at one year after diagnosis had a performance of 25% sensitivity, 90% specificity and a positive predictive value of 76%. Implementation of a decision support application at a rheumatology unit should include taking into account incentive structures, workflow and awareness, as well as informal communication structures. Prognosis: A considerable part of the variance in disease activity at one year after diagnosis could be explained by disease progression during the first three months after diagnosis. Using different types of knowledge – different expertise – prior to standardized data mining methods was found to be a promising when mining (clinical) data for new patterns that elicit new knowledge. Disease and disability: Women report more fatigue than men in early RA, although the difference is not consistently significant. Fatigue in early RA is closely and rather consistently related to disease activity, pain and activity limitation, as well as to mental health and sleep disturbance. Conclusion: A decision tree was designed to identify patients at risk of poor prognosis at one year after the diagnosis of RA. When constructing prediction rules for good or poor prognosis, including more measures of disease and disability progressions showed promise. Using different types of knowledge – different lenses of expertise – prior to standardized data mining methods was also a promising method when mining (clinical) data for new patterns that elicit new knowledge.
Introduktion: Reumatoid artrit (RA) är en kronisk inflammatorisk sjukdom. Dagens behandlingsstrategi bygger på tidiga multiprofessionella insatser för att reducera sjukdomsaktivitet och minska risken för framtida funktionshinder. Idag finns stora datamängder tillgängliga gällande medicinering och utfall vid RA. Dessa data erbjuder möjligheter att generera ny kunskap som kan användas för att forma beslutsstöd. Syfte: Att undersöka hur olika kliniska manifestationer vid tidig RA samvarierar med funktionshinder och sjukdomsaktivitet, att pröva metoder att ställa prognos vid tidig RA, och att analysera en kontext för beslutsfattande inom vård av kroniskt sjuka. Metod: Multivariat statistik och matematisk modellering, samt observationsstudier och fokusgruppsintervjuer. Resultat: Beslutsstöd: Ett beslutsträd utformades för att bestämma vilka patienter som har dålig prognos (måttlig eller hög DAS-28) ett år efter diagnos. Beslutsträdet hade 25 % sensitivitet, 90 % specificitet och ett positivt prediktivt värde på 76 %. Vid införande av beslutsstöd på en reumatologisk klinik befanns det nödvändigt att hänsyn tas till incitamentsstrukturer, arbetsflöde och samarbetsformer. Informella kommunikationsstrukturer kan också ha stort inflytande på klinisk praxis. Prognos: En betydande del av variansen i sjukdomsaktivitet ett år efter diagnos kan förklaras av sjukdomsprogression första tre månaderna efter diagnos. Att formalisera olika experters erfarenheter före standardiserade ”data mining” metoder är en lovande ansats när man letar efter mönster i (kliniska) databaser. Funktionshinder och sjukdomsaktivitet: Kvinnor rapporterar mer trötthet än män vid tidig RA, men skillnaden är inte konsistent över tid. Trötthet vid tidig RA är nära relaterat till sjukdomsaktivitet, smärta och aktivitets begränsningar, men också till mental hälsa och sömnstörningar. Slutsats: Ett beslutsträd har utformats för att predicera patienter med dålig prognos inom tidig RA. Studier av fler mått på sjukdoms- och funktionshindersprogression behövs vid konstruktion av prediktionsregler för god eller dålig prognos framledes. Att använda sig av kunskap från olika experter – olika experters glasögon – vid sökandet efter mönster i stora datamängder för att generera ny kunskap är en lovande metodik. Implementering av beslutsstöd bör göras under övervägande av incitamentsstrukturer, arbetsflöde och samarbetsformer.

Though the management of rheumatoid arthritis (RA) has recently been revolutionised, the optimal initial therapeutic regimen in the vital early stages is not known and critically the long-term effects of currently proposed regimens are not well documented. Patients with an expected poor prognosis would gain most from early treatment with highly effective but expensive new therapies; this highlights the need for better prognostic tools. Modern outcomes for RA should reflect patient expectations, for example, participation in work. In this thesis, evidence of the long-term effects of 2 initial therapeutic regimens in early RA was sought. Patients treated with an initial combination of methotrexate (MTX), ciclosporin A (CsA) and intraarticular glucocorticoids in early, poor prognosis RA required less biological agents after 7 years, compared with sulfasalazine (SSZ) monotherapy. The toxicity associated with CsA was reversible. Similarly patients that received an initial combination of infliximab plus MTX for early, poor prognosis RA had better disease control at 8 years than those who had initial MTX monotherapy. Dual energy X-ray absorptiometry (DXA) was tested as a prognostic tool in early RA given its reliability and easy availability. DXA measured hand bone loss during the first year of treatment was associated with radiographic progression at 6 years; however this did not perform better than a baseline radiograph. Imminent and actual job loss were proposed as patient reported outcomes in early RA. Patients receiving an initial combination of adalimumab plus MTX in early RA had a larger improvement in work related outcomes compared with MTX monotherapy. In summary initial therapeutic combinations in early RA can offer short and long-term benefits compared with monotherapy when measuring modern patient relevant and traditional outcomes. There is still a need for clinically useful prognostic tools in early disease.

Background: Orthopaedic surgery in Rheumatoid Arthritis (RA) is an established intervention of long-term disease and a surrogate marker of joint destruction. Methods: This thesis examines orthopaedic data from the Early RA Study (1986-1999, 9 centres, n=1465) and the Early RA Network (2002-2012, 23 centres, n=1236) with linkage to national datasets (Hospital Episode Statistics, National Joint Registry and Office of National Statistics). Clinical and laboratory measures and hand and foot radiographs were standardised and performed yearly in both cohorts. Disease modifying, glucocorticosteroid and biologic therapies reflected conventional practice and guidelines of the time frames examined. Recruitment years were grouped into 6 periods, interventions classified into major, intermediate and minor categories. Cost analysis was based on the Norfolk Arthritis Register (1989-date, n>5000). Results: A total of 1602 surgical procedures were performed in 770 patients (29%). Declines in the rates of hand/foot surgery from 1986-2011 (p<0.001) coincided with secular changes in therapy. No secular variation was seen for large joint replacements. Low haemoglobin predicted shorter time to both major and intermediate surgery (p<0.001). There were declines in median length of stay over time for large, intermediate and minor procedures (8,3,1 days respectively). The mean annual direct health cost per RA patient was £3,430 (over 50% representing medications). The COI of RA in England was estimated at £1.46 billion. Conclusions: This study has compiled the largest, longest and most extensively linked RA- related orthopaedic surgery database in the UK. The declines in intermediate-type surgery during recruitment periods where early and intensive treatments were employed, suggests the impact of these treatments. The thesis demonstrates the predictive power of standard clinical measures in the first year of disease on orthopaedic surgery up to 25 years later. It demonstrates the high economic burden of RA and could be used as a basis for future cost- effectiveness and cost-benefit analyses.

Apie 70% vaikų, sergančių lėtiniais artritais, suaugusiųjų amžių pasiekia su tam tikru negalios lygiu ir kasdienės veiklos apribojimu. Todėl ypač aktualu nagrinėti vaikams lėtinių artritų priežastis bei prognostinius veiksnius ankstyvose sąnarių ligos stadijose. Mūsų darbo tikslas buvo nustatyti ar ūminėje ligos fazėje nustatomų laboratorinių, imunologinių ir interleukinų (MRP8/14 (kalprotektinas), IL-6, IL-33) rodiklių pokyčiai, funkcinės būklės vertinimas bei ligos aktyvumas gali prognozuoti vaikams lėtinę sąnarių ligą. Atliktas tyrimas parodė, kad artritu susirgusiems vaikams MRP8/14 (kalprotektino) ir Il-6 koncentracijos buvo reikšmingai didesnės nei kontrolinės grupės vaikams tiek serume, tiek sinoviniame skystyje (p<0,01). Kalprotektinas ir IL-6 ūminėje ligos stadijoje stipriai koreliavo su ligos aktyvumo rodikliais (ENG, CRB, sąnarių pobūdžiu (poliartritu), rytiniu sąnarių sustingimu). Taip pat nustatėme, kad didelės kalprotektino (> 5785 ng/ml) ir IL-6 (> 5,5 pg/ml) koncentracijos ūminėje artrito stadijoje buvo nustatytos tiems pacientams, kuriems sąnarių liga įgavo lėtinę eigą. Vertinome tai, kaip reikšmingus lėtinės sąnarių ligos kriterijus. Šiame darbe sergančių artritų vaikų funkcinė būklė ir vaiko gyvenimo kokybė pirmą kartą Lietuvoje buvo įvertinta naujai įdiegiamu ne tik Lietuvoje, bet ir pasaulyje, įvairiapusiu jaunatvinių artritų vertinimo klausimynu JAMAR, bei duomenys palyginti su seniau Lietuvoje naudojamu vaiko sveikatos būklės vertinimo klausimynu... [toliau žr. visą tekstą]
The earlier studies proved that nearly 70% of children with chronic arthritis reach the adulthood with a certain level of disability and restriction of daily activities. Therefore, it is very important to analyse the causes of arthritis and prognostic factors in the early stages of disease. The aim of our study was to determine whether the changes of laboratory, immunological and interleukins (MRP8/14 (calprotectin), IL-6, IL-33) indexes, assessment of functional condition, and disease activity may predict a chronic arthritis in children. The study showed that MRP8/14 (calprotectin) and Il-6 concentrations in the serum and synovial fluid of children with arthritis were significantly higher than in the control group of healthychildren (p<0.01). During the acute stage of disease, calprotectin and IL-6 concentrations strongly correlated with variables of disease activity (ESR, CRP, polyarthritis, morning stiffness of joints). Also, the analysis showed that high concentrations of calprotectin (> 5785ng/ml) and IL-6 (> 5.5 pg/ml) at the acute stage of arthritis were determined for those patients, whose were developed chronic arthritis. It was evaluated as significant criterion of the chronic joint disease. For the first time in Lithuania, the functional ability and the quality of life in children with arthritis were assessed using a newly introduced multidimensional assessment questionnaire for juvenile arthritis (JAMAR), and data was compared... [to full text]

The aims of my PhD project were a) to determine the levels of C1q-binding proteins (gC1qBP and calreticulin) in (i) normal serum, (ii) serum/plasma samples of patients diagnosed with rheumatoid arthritis and systemic lupus erythematosus and (iii) synovial fluid samples of patients diagnosed with rheumatoid arthritis. For this, coding cDNA sequences for gC1qBP and calreticulin were cloned and expressed recombinant proteins were purified and used to develop functional ELISA assays. It was observed that calreticulin levels were significantly increased in the synovial fluid samples of patients diagnosed with rheumatoid arthritis as compared to synovial fluid samples of patients diagnosed with osteoarthritis. gC1qBP was found to be significantly increased in the serum samples of patients diagnosed with systemic lupus erythematosus and decreased in synovial fluid samples of patients diagnosed with rheumatoid arthritis, as compared to serum samples of healthy control individuals. b) to establish functional assays to measure complement activation in human, murine and guinea pig sera. I investigated for potential MBL ligands and demonstrated MBL binding and lectin pathway activation using the pneumococcal vaccine Pneumovax II and Acanthamoeba (whole cells) trophozoites and cysts. CR1 has been described as a ligand for MBL. I tested this hypothesis using functional ELISA assays. In contrast to conclusions in a previous report of another research group, my results show that soluble CR1 binds to C1q but not to MBL. The results presented in my thesis also provide strong evidence that CR1 appears not to interact directly with MBL or MBL-mediated lectin pathway activation as the addition of soluble CR1 to my lectin pathway activation assay has no effect whatsoever on C4 cleavage. Nevertheless, sCRl regulates lectin pathway activation further downstream and significantly inhibits lectin pathway mediated C3 cleavage, most likely by the decay accelerating and co-factor activity of sCRl in the factor I-mediated inactivation of either C4b or C3b. Using the C3 cleavage assay and murine strains deficient in C1q, factor B and factor B/C2, I showed the importance of the amplification loop of the alternative pathway in complement activation. Finally, using the C3 cleavage assay with guinea pig serum deficient in complement component C4, it was demonstrated that MASP-1 does not appear to be an effective enzyme in cleaving C3, as proposed by others.

Afin de modéliser l'évolution de l’infection par le chikungunya (CHIK), son impact, et les facteurs pronostiques de chronicité, nous avons travaillé en trois parties. L'impact à long terme de l’épidémie de CHIK en 2005-2006 à la Réunion a été estimé en calculant la proportion de patients en phase chronique au cours du temps et la charge globale de morbidité du CHIK par la méthode des années de vie ajustées sur l'invalidité (méthode DALY de l’OMS, qui prend en compte les années de vie perdues en raison de la mortalité prématurée et des années de vie vécues avec une incapacité). Ainsi entre 51,2 et 65,3% des patients étaient estimés symptomatiques après 1 an et 0% à15,2% après 5 ans. Le total d’années de vie en bonne santé perdues à la Réunion a été estimé à 65-73/1000 personnes, 55,5% des pertes concernant la population active (les 20 à 60 ans), et 86% étant dues à la persistance de rhumatismes post-CHIK (phase chronique). Les facteurs pronostiques de la persistance de rhumatismes et de l’altération de la qualité de vie (QdV) à long terme (30 mois) ont été étudiés dans une cohorte des gendarmes dont 25% étaient infectés (CHIK+). Etre CHIK+, avoir des comorbidités et un moral déprimé pendant la phase aiguë étaient prédictifs de la persistance d’arthrite comme d’arthralgies. De plus, la présence d’arthralgies ou arthrite à six mois était très prédictive de la persistance des mêmes rhumatismes à 30 mois
To model the evolution of chikungunya virus (CHIK) infection, its impact and the prognostic factors of post-CHIK rheumatism and quality of life, we worked in three parts. The long-term impact of the 2005-2006 CHIK outbreaks in Reunion Island was estimated by calculating the proportion of chronic patients over time and the global burden of CHIK using the Disability Adjusted Life Years (DALY) method. This method sums the years of life lost due to premature mortality and the years lived with disability. Between 51.2 and 65.3% of patients were estimated chronic after 1 year and 0%-15.2% after 5 years. The global disease burden of CHIK was estimated 65-73 DALYs/1000 persons, 55.5% concerning the active population (20-60 years old), and 86% due to persistence of post-CHIK rheumatisms. Prognostic factors of the long-term (30 months) rheumatisms and impaired quality of life (QoL) were studied in a cohort of French army policemen (25% CHIK infected: CHIK+). Being CHIK+, suffering of comorbidity and having depressed mood during the acute stage were predictive for both persistent arthritis and arthralgias at 30 months. In addition, suffering of either arthralgias or arthritis at six months was predictive of the same symptoms at 30 months. Determinants of impaired QoL were CHIK infection and comorbidity, in addition to older age, work-stoppage during the acute infection and arthritis at 6 months for the QoL physical component, and depressed mood at 6 months for the mental health component.Association between the severity of initial CHIK-stages and recovery were studied using multiple correspondence analysis (MCA)

Psoriatic Arthritis (PsA) is an inflammatory arthritis associated with psoriasis that leads to progressive joint damage. Genetic variants in the Major Histocompatibility Complex (MHC) region on human chromosome 6p, especially Human Leucocyte Antigen (HLA), are the most important genetic risk variants associated with susceptibility to PsA. I aimed to investigate the heritability of PsA and to determine the association between HLA polymorphisms with susceptibility and severity of PsA. I first validated the new CASPAR classification criteria for PsA in patients in with both early and established disease. Subsequently, I demonstrated that PsA as defined by the CASPAR criteria has a high recurrence risk ratio. In a large case-control and family-based association study, I demonstrated that the class I HLA alleles, HLA-C*12/B*38, -B*27 and -C*06/B*57 are associated with increased susceptibility to PsA. HLA class I molecules biologically interact with Killer-cell Immunoglobulin-like Receptors (KIR) on Natural Killer (NK) to influence immune response. I demonstrated that KIR2DS2 and HLA C group 2 and HLA-B Bw4 were associated with PsA susceptibility. Further analyses of PsA cases with Type II psoriasis and with dactylitis suggested that HLA-C*02, -B*27, -B*38 and KIR2DS2 may be markers of musculoskeletal manifestations of PsA. Furthermore, using longitudinal data, I demonstrated that HLA-B*39, -B*27, -A*02 and KIR3DS1 are associated with peripheral joint damage progression whereas the alleles –DQB1*0604, -C*04 and –B*60 are associated with less damage progression. HLA-C*02, -C*12, -DQB1*0609 and KIR2DS1 are associated with higher risk of sacroiliitis, and HLA-B*27 with syndesmophytes. HLA-A*29 was associated with reduced risk of development of both sacroiliitis and syndesmophytes. These studies indicate that HLA alleles and KIR genes are important in PsA susceptibility and severity and suggest that CD8+ T cells and NK cells that modulate the innate and adaptive immune response play an important role in the susceptibility and severity of PsA.

碩士
國立中正大學
醫療資訊管理研究所
101
Rheumatoid arthritis is a chronic systemic inflammatory disease of unknown etiology that primarily targets synovial tissues. In clinical practice, initial treatments are usually chosen according to the degree of disease activity at baseline, and adapted according to a step-up strategy. This study attempts to the professionals opinion combined with data mining techniques, namely logistic regression model, decision tree and support vector machines to analyzing for all rheumatoid arthritis patients which has no classified by medication to predicting with or without complications, and respectively analyzing for rheumatoid arthritis and rheumatoid arthritis accompanied complications(cardiovascular diseases, hepatitis, alcoholic hepatitis and end-stage renal disease) of patients which has classified by medication to predicting ESR whether to reach normal. The obtained data were analyzed to construct different classification, by compare classification prediction accuracy rate to selecting the best performance prediction mode, to predicting the prognosis of rheumatoid arthritis and analysis of the results. In this study, data mining technique combined with the professional opinion in order to propose the best therapeutic strategy for patients.

Aim: To describe the predictive validity of reaching low disease activity (LDA) at 1 year on future disability and joint damage in patients with early rheumatoid arthritis (ERA). Methods: First a systematic literature review of prognostic studies assessing the association between disease activity and functional or radiographic outcomes in ERA was performed. Then data from the Study Of New-Onset RA (SONORA) were used to evaluate the impact of year-one LDA on 3-year disability and 2-year radiographic progression using multivariate regression analyses. Results: Our review demonstrated evidence for relationship between baseline disease activity and future disability and join damage. However evidence for the impact of early treatment response on long-term outcomes in ERA is sparse. Analysis of 984 patients showed year one LDA predicts lower HAQ (p<.0001) and less damage (p=0.04) in future. Conclusion: Reaching LDA early is associated with better long-term functional and radiographic outcomes in patients with early RA.

M.A. (Clinical Psychology)
Rheumatoid arthritis, lithe great crippler" 1 has now established itself firmly in the category 'psychosomatic disease' and a psychosomatic approach is used when considering the aetiology of the disease and often the therapy and prognosis of the patient as well. The rehabilitation of the afflicted patient is the central concern of medical and para-medical personnel engaged in rheumatology. The patient's motivation for rehabilitation is generally considered to be the single most important factor affecting the rehabilitation process. The task of assessing this motivation falls to the psychologist...

ABSTRACT: Objectives: This study aimed to confirm whether 15 single nucleotide polymorphisms (SNPs) of selected genes are also associated with susceptibility for Juvenile idiopathic Arthritis (JIA) in thePortuguese population. Methods: Our study was conducted on Reuma.pt, the Rheumatic Diseases Portuguese Register, which includes patients with JIA receiving biological therapies and synthetic Disease Modifying Anti Rheumatic Drugs (DMARDs) since June 2001. Fifteen SNPs were investigated using Taqman® SNP genotyping assays in 291 Portuguese patients with JIA and 300 ethnically matched healthy controls. Results: Prior to Bonferroni correction for multiple testing, significant genotype association between one SNP and overall group of JIA was observed (PTPN22 rs2476601). In subgroup analysis, associations between six SNPs and the subgroup of patients with rheumatoid factor (RF)-positive Polyarticular (PTPN2 rs7234029), Extended oligoarticular (PTPN22 rs2476601), Systemic (PTPRC rs10919563, ANGPT1 rs7151781 and TNF rs361525) and Psoriatic JIA (IL2RA/CD25 rs2104286) were found. After Bonferroni correction for multiple testing, 3 genotype associations remained significant in the subgroup of patients with RF-positive polyarticular JIA (PTPN2 rs7234029 [corrected P 0.026]), extended oligoarticular (PTPN22 rs2476601 [corrected P 0.026]) and systemic JIA (ANGPT1 rs7151781 [corrected P 0.039]). Conclusion: Our results provide additional evidence for an association between polymorphisms in genes PTPN2, PTPN22 and ANGPT1 and the risk of RF-positive polyarticular, extended oligoarticular and systemic JIA, respectively, in a Portuguese population.