B-cells of the rheumatoid synovial tissue are a constant part of and, in some histopathological subtypes, the dominant population of the inflammatory infiltrate, located in the region of tissue destruction. The pattern of B-cell distribution and the relationship to the corresponding antigen-presenting cells (follicular dendritic reticulum cells: FDCs) show a great variety. B-cells may exhibit (i) a follicular organization forming secondary follicles; (ii) follicle-like patterns with irregularly formed FDC networks, and (iii) a diffuse pattern of isolated FDCs. Molecular analysis of immunoglobulin VH and VL genes from human synovial B-cell hybridomas and synovial tissue demonstrates somatic mutations due to antigen activation. The FDC formations in the synovial tissue may therefore serve as an environment for B-cell maturation, which is involved in the generation of autoantibodies. An autoantibody is defined as "pathogenic" if it fulfills the Witebsky-Rose-Koch criteria for classical autoimmune diseases: definition of the autoantibody; induction of the disease by transfer of the autoantibody; and isolation of the autoantibody from the disease-specific lesion. B-cells from rheumatoid synovial tissue show specificity for FcIgG, type II collagen, COMP, sDNA, tetanus toxoid, mitochondrial antigens (M2), filaggrin and bacterial HSPs. The contributions of these antigens to the pathogenesis of RA are still hypothetical. A possible contribution could derive from crossreactivity and epitope mimicry: due to crossreaction, an antibody directed originally against a foreign infectious agent could react with epitopes from articular tissues, perpetuating the local inflammatory process. The characteristic distribution pattern, the localisation within the area of tissue destruction, the hypermutated IgVH and IgVL genes, and their exclusive function to recognize conformation-dependent antigens suggest a central role for B-cells in the inflammatory process of rheumatoid arthritis. Therefore, the analysis of synovial B-cell hybridomas and experimental expression of synovial IgVH and IgVL genes will help to characterise the antigens responsible for the pathogenesis of rheumatoid arthritis. In the present study 55 IgVH genes amplified from 3 different anatomical regions of a RA patient were analysed adding further information on synovial B-cell maturation and recirculation in RA. This analysis demonstrated somatically mutated IgVh genes in all different regions with amino acid deletions and mixed IgVh molecules, suggesting the existence of a novel pathway to generate (auto)antibody specificities. The comparison of amino acid sequences of amplified genes belonging to the VH1 family (with predominantly the same germline counterpart) exhibited a strong homology, indicating an apparently conserved mutational pattern. This suggests that the number of antigens activating B-cells in the different locations is restricted. The most striking result was the finding of clonally related sequences in different anatomical regions indicating a recirculation of activated B-cells between the different affected joints. Also in the present study a synovial B-cell hybridoma was analyzed for its specific recognition of cartilage antigens. A heptameric peptide of cartilage oligomeric protein (COMP) could be defined as the target structure. The IgVH-gene (IgHV4-59*01) of the IgG2l hybridoma has somatically mutated genes with high R/S values in the CDR regions (9:2). Thus, indicating that this hybridoma originates from a synovial B-cell which has been antigen activated/selected for its affinity. To analyse the presence of the clonotypic IgHV4-59*01 sequences in other cases of RA and osteoarthritis (OA) synovitis, primers specific for the CDR3 rearrangement of this hybridoma were used. The clonotypic and clone related sequences (98 per cent ± 1 per cent homology) could only be detected in synovitis of RA cases but not in OA cases indicating that this B-cell is specific to RA synovitis. The identified heptameric peptide of COMP was used in a peptide ELISA to analyse whether there is a specific binding in RA serum samples. Serum samples (IgG) from RA patients (n=22) showed a significant higher efficiency to the COMP heptamer than the OA sera (n=24) and the age matched healthy controls (n=20) (for both p<1x10-4, Students t-test). The specificity of this B-cell hybridoma may therefore be defined as RA specific. Since COMP is restricted to cartilage and tendons which are organs specifically affected in RA this COMP specific autoantibody represents the first organ specific autoantibody in RA. The IgG2 COMP specific autoantibody with somatically mutated IgVH genes is different from germline encoded, antigen clearing IgM autoantibodies and may therefore be directly involved as an "arthritogenic autoantibody" in cartilage and tendons destruction by complement activation. / B-Zellen des rheumatoiden Synovialgewebes sind einerseits ein konstanter Bestandteil und andererseits in einigen histopathologischen Subtypen sogar die dominante Bevölkerung des entzündlichen Infiltrates, welches sich in direkter Nähe des zerstörten Gewebes befindet. Das Strickmuster der B-Zellen-Verbreitung und die Verbindung zu den korrespondierenden antigenerzeugenden Zellen (follikuläre dendritische Zellen, sprich: FDC) zeigen eine große Vielfalt. B-Zellen können a) in der Form eines follikulären Verbandes sich bildender Sekundärfollikel; b) als follikelähnliche Muster mit unregelmäßig geformten FDC-Netzwerken und c) als ein diffuses Muster isolierter FDCs auftreten. Molekularanalysen der immunglobulinen VH- und VL-Gene von menschlichen synovialen B-Zell-Hybridomen und Synovialgewebe zeigen somatische Mutationen aufgrund von Antigenaktivierung auf. Die FDC-Schichten im Synovialgewebe dürften daher als ein Nährboden für B-Zell-Reifung dienen, welche wiederum in den Prozeß der Autoantikörperbildung eingreift. Ein Autoantikörper wird als "pathogenisch" bezeichnet, wenn er das Witebsky-Rose-Koch-Kriterium für klassische Autoimmunkrankheiten erfüllt: Bildung des Autoantikörpers; Einleitung der Krankheit durch Übertragung des Autoantikörpers und Isolation des Autoantikörpers vom krankheitsspezifischen Entzündungskomplex. B-Zellen aus rheumatoidem Synovialgewebe zeigen Spezifität für die Fc-Region von lgG; Typ II Kollagen; COMP; sDNA; Tetanustoxin; mitochondrische Antigene (M2); Fillaggrin und bakterielle HSPs. Der Beitrag dieser Antigene zur Pathogenese in der RA ist weiterhin hypothetisch. Ein möglicher Beitrag könnte aus der Kreuzreaktion und Epitopähnlichkeit aufgrund dieser Kreuzreaktion herrühren. Ein Antikörper, der ursprünglich gegen einen fremden Infektionsherd gerichtet war, könnte mit Epitopen aus Gelenkgewebe reagieren und somit den lokalen Entzündungsprozeß aufrechterhalten. Das charakteristische Verteilungsmuster, die Lokalisierung inmitten des zerstörten Gewebes, die hypermutierten IgVH- und IgVL-Gene und ihre ausschließliche Funktion, strukturabhängige Antigene zu erkennen, läßt auf eine zentrale Bedeutung der B-Zellen im Bezug auf den Entzündungsverlauf in der rheumatoiden Arthritis schließen. Deswegen wird die Analyse synovialer B-Zellen-Hybridome und die experimentelle Erkundung synovialer IgVH- und IgVL-Gene eine große Hilfe zur Charakterisierung der Antigene sein, welche verantwortlich für die Pathogenese in der RA sind. In dieser Studie wurden 55 IgVH-Gene analysiert, die von 3 verschiedenen anatomischen Regionen eines RA-Patienten amplifiziert wurden, wodurch man zusätzliche Informationen über synoviale B-Zellen-Reifung und -Rezirkulation in der RA erhielt. Diese Analyse zeigte somatisch mutierte IgVH-Gene in allen verschiedenen Regionen auf, mit Aminosäuredeletionen und gemischten IgVH-Molekülen, die Grund zur Annahme geben, daß eine neue Möglichkeit existiert, (Auto-) Antikörperspezifizierungen zu generieren. Der Vergleich von Aminosäuresequenzen amplifizierter Gene, die zur VH1-Familie gehören (mit überwiegend denselben Keimbahngenen) zeigten eine starke Homologie auf und wiesen auf ein scheinbar erhaltenes Mutationsmuster hin. Dieses läßt annehmen, daß die Anzahl der Antigene begrenzt ist, die B-Zellen in den verschiedenen Regionen aktivieren. Das markanteste Ergebnis war das Auffinden klonal verwandter Sequenzen in verschiedenen anatomischen Regionen, die darauf hinweisen, daß aktivierte B-Zellen zwischen den verschiedenen befallenen Gelenken rezirkulieren. Desweiteren wurde in dieser Studie ein synoviales B-Zellen-Hybridom analysiert bezüglich seiner spezifischen Erkennung von Knorpelantigenen. Ein heptameres Peptid des COMP könnte als eine mögliche Zielstruktur definiert werden. Die IgVH-Gene (IgHV4-59*01) des IgG2?-Hybridomes besitzt somatisch mutierte Gene mit hohen R/S-Werten in den CDR-Regionen (9.2). Somit weist dies darauf hin, daß dieses Hybridom aus einer synovialen B-Zelle stammt, welche aufgrund ihrer Affinität antigen-aktiviert wurde. Um das Vorkommen der klonotypischen IgHV4-59*01-Sequenzen in anderen Fällen der RA und Osteoarthritis (OA)-Synovitis zu analysieren, wurden Primer benutzt, die spezifisch für die CDR3 dieses Hybridomes sind. Die klonotypischen und klonal verwandten Sequenzen (98 Prozent ± 1 Prozent Homologie) konnte nur in Fällen der RA-Synovitis erkannt werden, jedoch nicht bei OA-Fällen, was darauf hinweist, daß diese B-Zelle spezifisch für die RA-Synovitis ist. Das identifizierte heptamere COMP-Peptid wurde in einer Peptid-ELISA verwendet, um festzustellen, ob es eine spezifische Bindung in RA-Seren gibt. Seren (IgG) von RA-Patienten (n=22) zeigten eine bedeutend höhere Wirksamkeit des COMP-Heptamers an als in OA-Seren (n=24) und den altersabhängigen gesunden Kontrollen (n=20); (für beide p<1x10-4; Students t-Test). Die Spezifizierung dieses B-Zellen-Hybridomes könnte daher als RA-spezifisch angesehen werden. Da COMP sich auf Knorpel und Sehnen beschränkt - welches hauptsächlich in der RA betroffene Organe sind - repräsentiert dieser COMP-spezifische Autoantikörper den ersten organspezifischen Autoantikörper in der RA. Der IgG2-COMP-spezifische Autoantikörper mit somatisch mutierten IgVH-Genen unterscheidet sich von dem der antigenvernichtenden IgM Autoantikörper und könnte daher direkt in die Knorpel- und Sehnenzerstörung durch Komplementaktivierung miteinbezogen sein, als ein "arthritogener Autoantikörper".

The Leukocyte Immunoglobulin-like Receptors (LILRs) are a family of receptors that is broadly expressed on all leukocytes and have the ability to regulate their function. A substantial amount of evidence suggests that LILRs may be involved in immune homeostasis but also immune dysregulation. We therefore studied the role of LILRs in relation to the autoimmune disease, rheumatoid arthritis (RA). RA is a chronic and systemic inflammatory disease involving inflammation of the joints affecting the synovial membrane, cartilage and bone. Much of the tissue damage is a result of an inappropriate immune response within the joint space caused by the unwarranted activation of leukocytes. Here were report that LILRA2 (an activating receptor) that has been previously shown to be highly expressed in the rheumatoid synovium, induces the production of pro-inflammatory cytokines TNF-α, IL-1, IL-6, IFN-γ and IL-10 in primary monocytes. These cytokines are known to have an important role in the pathogenesis of RA indicating a pathway by which LILRA2 exacerbates RA. Co-ligation of LILRB4 (an inhibitory receptor) with LILRA2 abolishes cytokine production suggesting that LILRB4 is able to suppress the function of LILRA2. Expression of both LILRA2 and LILRB4 are regulated by inflammatory cytokines and LPS, indicative of a feedback mechanism. There is also cross-talk between LILRs and TLR4 as co-stimulation with LPS and either LILRA2 or LILRB4 inhibits cytokine production. A differential expression of LILRs has also been identified on lymphocytes of patients with RA whereby an increase of LILRA1 (activating) and LILRB1 (inhibitory) expressing circulating lymphocytes is present in RA patients when compared to healthy control subjects. From these studies, we propose that LILRs have a functional role in RA by regulating local and systemic inflammation. The presence of LILRA2 in the RA joint is detrimental since its potent ability to induce inflammatory cytokines, particularly TNF-α, can initiate leukocyte recruitment and activation of proteases. Along with TLR4, LILRA2 and LILRB4 have the potential to moderate the innate immune system via regulation of cytokine production. Furthermore, suppression of LILRA2 function may serve as a therapeutic tool in many inflammatory diseases.

Bibliography: leaves 250-284. / xviii, 284 leaves : ill., plates (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, School of Molecular and Biomedical Science, Discipline of Microbiology and Immunology, 2004

The purpose of this investigation was to determine the validity and reliability of the Nicholas Manual Muscle Tester (NMMT), a portable dynamometer, as a measure of the isometric strength in women with arthritis. Female subjects (N=13; 66 �� 13.89 yrs.) with arthritis were tested for isometric muscle strength on the shoulder and hip (abduction, adduction, flexion, extension). Subjects were tested on three separate days using NMMT and Kincom 500-H dynamometers. Each subject performed three maximal isometric contractions for each joint action. A visual analog pain scale was used to determine level of pain prior to testing. Reliability values based on intraclass correlations coefficients (R) ranged from .85 to .93., with the exception of shoulder abduction being .49. Validity was determined correlating the mean value of the NMMT score with corresponding Kincom isometric measure. Pearson product moment correlations ranged from (r) .02 to .86, with 4 of 8 values meeting .05 level of significance. Correlation coefficients for pain and isometric force values were inconclusive and ranged from -.305 to .218. Major conclusions were: a) NMMT had high test-retest reliability in this sample; b) NMMT provides little criterion evidence of validity with the Kincom for most movements of hip and shoulder; c) level of pain was not a significant factor in subject reliability. / Graduation date: 1995

Background. Rheumatoid arthritis (RA) is an autoimmune disease mainly affecting the joints but has also extra articular manifestations and an increased cardiovascular (CV) co-morbidity. Rheumatoid factor (RF) and antibodies against citrullinated proteins/peptides (ACPA) are diagnostically important and are related to a more severe disease. The aetiology is unknown but RA is considered a complex disease caused by both genetic and environmental factors. The heritability is estimated to be 60% with the main contribution from the HLA region. The relative homogeneity of the population in northern Sweden due to low immigration and founder effects has shown to be suitable for genetic studies. Objectives. The aim of this thesis has been to identify genes contributing to the susceptibility of RA and the CV co-morbidity in particular. To achieve this, multi-case families from the four northern most counties of Sweden were collected for linkage studies to identify susceptibility genes. Association studies with genetic polymorphisms in genes, involved in inflammation or being of importance for atherothrombotic manifestations (ATM) in the general population, were performed in RA-patients concerning ATM e.g. myocardial infarction, angina pectoris with intervention, stroke/TIA, deep vein thrombosis/pulmonary embolism (DVT/PE) at follow-up. Methods &amp; Results. 47 families with 134 affected and 216 unaffected relatives were included in a genome-wide linkage study (GWL) performed with microsatellite markers at an average of 10cM resolution analysed using ABI PRISM 3730 DNA sequencer and non-parametric multipoint linkage in the Merlin program. Eight linked loci were identified with HLA as the most significant and a novel region on chromosome 14. In a follow-up analysis on a custom Illumina chip, with 13 additional families, yielding a total of 198 affected and 197 unaffected relatives. The majority of the 1536 single nucleotide polymorphisms (SNPs) used in the Illumina follow-up analyses was focused on chromosome 14. Statistical analyses with linkage and transmission disequilibrium test narrowed the region to 4 cM, a region containing multiple plausible RA candidate genes (Paper I). In Paper II  serum samples from 163 affected and 157 first degree relatives were analysed with EliA ACPA assay on ImmunoCAP250 for ACPA (IgA, IgG, IgM) and RF (IgA, IgM) isotypes. Both concentrations and frequencies were increased among the relatives compared with controls but lower compared with RA-patients and with a different relative distribution of the isotypes. The genetic contribution to ATM was studied in Paper III and IV using selected SNPs analysed using ABI PRISM 7900HT sequence detector system. In Paper III, RA-patients (n=467) were compared with age and sex matched controls (n=696) with respect to SNPs in tumor necrosis factor receptor II (TNFRII)(M196R), ß-fibrinogen -455 (G-455A), plasminogen activator inhibitor type-1 (PAI-1) (4G/5G) and Factor XIIIA (Val34Leu). Hypertension was predicted by TNFRII R allele and to a higher extent in combination with the A-allele in ß-fibrinogen. The 4G allele in PAI-1 was more frequent in patients with ischemic heart disease (IHD) and the FXIIIA Leu34 variant in patients with DVT/PE. In Paper IV, the minor allele of the polymorphism in growth differentiation factor 15 (GDF15) was found to be associated with RA (n=696) per se but also to ATM, a SNP in the 9p21.3 locus was also associated with ATM. A significant association to stroke was found in female patients homozygote for the minor allele of GDF15. Stoke among male patients was significantly associated with carrying the major allele of two SNPs in the CD40 gene. DVT/PE was associated with the minor allele of GDF15. Conclusion. A novel locus on chromosome 14 of importance for RA susceptibility in northern Sweden was found. The minor allele of TNFRII separately and together with the minor allele of ß-fibrinogen -455 was associated with hypertension and the 4G allele in PAI-1 was associated with IHD and  the Leu34 variant was associated with DVT/PE in RA patients. The GDF15 minor allele was associated with RA per se, ATM and DVT/PE in RA patients and a genotype in the SNP on 9p21.3 was associated with ATM. Stroke among females was associated with GDF15 and stroke among males with two SNPs in CD40.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation eventually leading to the destruction of cartilage and bone. The aetiopathogenesis is not completely understood, but previous studies have shown that the disease is multifactorial with genetic, environmental and hormonal factors involved. Immune cells, e.g., T- and B-cells, and macrophages, migrate into the joints, with increased expression of numerous soluble factors such as cytokines, chemokines and adhesion molecules functionally active both locally and systemically. Analyses of blood samples from the Medical Biobank in Umeå from individuals before the onset of symptoms of joint disease showed that anti-citrullinated protein/peptide antibodies (ACPA) preceded the development of disease by years and this finding has been confirmed by other studies.                                         The aim of this thesis was to identify signs of activation of the immune system analysed as up-regulation of pro- and anti-inflammatory cytokines, sero-positivity for autoantibodies, and genetic factors identified as relevant for the development and disease progression of RA. The concentrations of 30 cytokines and chemokines were measured in blood samples from individuals before the onset of symptoms, and when diagnosed with RA, together with population-based matched controls using a multiplex system. The predictive value of different isotypes (IgG, IgA, and IgM) of ACPA and rheumatoid factor (RF) before onset of symptoms and different types of ACPA (e.g., mutated citrullinated vimentin, MCV) were analysed for disease development and progression in patients with early RA and controls from Northern Sweden. These factors were related to the genetic markers, HLA- shared epitope (SE) alleles and the 1858C/T polymorphism of the protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene.                            In paper I, it was shown that in individuals who later developed RA (i.e., pre-patients) the levels of several cytokines and related factors that represent the adaptive immune system (Th1, Th2, and T regulatory cell related factors) were significantly elevated compared with controls, whereas, after the onset of disease the involvement of the immune system was more general and widespread. In paper II, the presence of different isotypes (IgM, IgA and IgG) of ACPA in pre-patients, patients and controls was evaluated showing that both the IgG and IgA isotype predicted the onset of RA by years with the IgG isotype having the highest predictive value. In paper III, the association of the 1858T variant of PTPN22 with RA was confirmed. Furthermore, the association was restricted to autoantibody positive disease and this variant was correlated with an earlier age for disease onset. In paper IV, anti-MCV antibodies were identified as being associated with a more severe disease course of RA, measured by disease activity score, erythrocyte sedimentation rate, and swollen joint count over time compared with anti-CCP2, anti-CCP3, and anti-CCP3.1 antibodies.                                                                                                In conclusion, individuals who later developed RA had increased concentrations of inflammatory markers reflecting an activation of the immune system years before the clinical symptoms of the disease developed. Also, the presence of ACPA of IgG and IgA isotype prior to disease onset predicted the development of RA. The PTPN22 1858T variant was associated with sero-positive RA and anti-MCV antibodies were associated with a higher inflammatory activity compared with anti-CCP2, -CCP3 and -CCP3.1 antibodies. These findings together present a possibility to better predict the development and progression of RA.

Abstract As a matter of fact, for those producers in medicine industry who runs multi-national business, have to promote two to three kinds of new medicine on the market enabling to maintain two-digit growth. However, the new products (medicine) be certified for marketing is not able to follow the step and progress what have been researched and developed. The ratio of success for the research and development of new medicine as well as the quantity of the marketing for new medicine eventually become the most critical factor of determination for marketing value of all major international medicine producers. This study will be preceded with discussion of reference document, collection of secondary information, and case study to describe the marketing strategy, that mainly focus on the analysis to the Rheumatoid Arthritis biological products and its relating information to further find out the ¡§Pattern of Successful Marketing for New Medicine¡¨. Moreover, it might sort out the key factor of successful marketing for many kinds of biological products for the Rheumatoid Arthritis. Eventually, the study is trying to propose the successful application of marketing for new medicine to maximize the opportunity of success and potentiality. There are some key factors like planning and preparation for successful marketing of new medicine, which normally covers the complex of multi-professional filed. The combination of marketing is the tool to achieve the target market. These tools are divided into four classifications, named as ¡§Marketing 4 P¡¨: They are respectively Product, Price, Place and Promotion. This study adopts 4 P of Promotion Management of Marketing to discuss the strategy of new medicine marketing and investigate the deployment of marketing strategy in Taiwanese medicine marketing. The study indicates the discussion of For 4 P can provide marketing personnel with a clear direction, to map out the thinking mode of complete strategy for new medicine marketing in order to diminish the resistance of marketing, and facilitate the success of new medicine Launch. Key Words: New Medicine Launch, Marketing Strategy, Rheumatoid Arthritis, 4 P

Rheumatic diseases are often chronic and involve a lifetime of suffering. The focus of rheumatology care is to support patients to manage their lives and master their disease. Healthcare providers and patients have different views on the consequences of living with rheumatic diseases and patients are reporting unmet healthcare needs. There is a need to integrate providers' perspective to develop the quality of rheumatology care. The aim was to explore healthcare providers' experiences of their interaction with patients in their management of RA. Interviews with 18 providers from different clinical settings were analysed in accordance with the grounded theory method. A core category; Delivering knowledge and advice was found to be the most important task and involved providing the patient with information about the disease and appropriate forms of treatment. Healthcare providers' attitudes and patients' responses influenced the outcome of the delivery of knowledge and advice and three dimensions emerged; completed delivery, adjusted delivery and failed delivery. There were differences in the providers' experiences in their interaction with patients as well as in reflections on their role as the delivering part. There could be difficulties in the interaction when patients' expectations and preferences were not taken into account when giving advice. These findings highlight the importance of developing rheumatology care, as no provider or patient benefits if the delivery of knowledge and advice becomes a failed delivery. The healthcare organization must acknowledge the difficulties involved in the interaction with patients in their management of RA and find methods to develop a more person-centred approach to care.

Aim: To generate a theoretical model how patients experience their management of rheumatoid arthritis (RA) in everyday life.Method: An explorative design with the grounded theory approach was used by interviewing 16 informants with RA.Results: The generated theoretical model emerged in a core category- Striving for a good life with two categories; making use of personal resources and grasping for support from others, which formed the base of managing RA. When relating these categories together, four dimensions emerged which characterised patients’ different ways of managing RA: mastering, relying, struggling and being resigned.Discussion: The management of RA incorporated the use of personal resources and the grasping for support from others. Both self-management strategies and patients’ need of support were highlighted as aspects that were of importance when managing RA. Patients’ experiences of their need of support to manage RA give extended knowledge that is of importance for nurses and other healthcare providers. The relationship between patients and healthcare providers is always the key to a good encounter. Interventions to increase self-management in RA have to incorporate this knowledge when trying to increase patients’ self-efficacy and with their experience of support

Purpose: The primary purpose of this project was to determine the effect of aquatic exercise and aquatic exercise combined with an education group program on decreasing both psychosocial and physical fall risk factors in community-dwelling older adults with hip osteoarthritis (OA). Secondary purposes were to 1) describe fall risk, history and nature of falls and near-falls in older adults with hip OA, 2) determine the association of the timed up and go test (TUG) to history of falls and near-falls, 4) explore the relationship of both psychosocial and physical factors to history of falls and near-falls, and 5) evaluate the role of falls-efficacy in predicting balance performance. Methods: Participants were recruited from the community and screened for presence of hip osteoarthritis and fall risk. Baseline fall history and a battery of measures for balance, muscle strength, functional ability and falls-efficacy were administered. Participants were then randomly assigned to one of three groups: Aquatic Exercise, Aquatic Exercise and Education or a Control Group. The interventions were twice per week for 11 weeks. Fall risk factors were measured after 11 weeks. Study 1 described history of falls and near-falls and evaluated the association of the TUG screening test with fall and near-fall history. Study 2 summarized the relationships of physical and psychosocial fall risk factors and identified the primary predictors of fall risk, based on associations with fall history. Study 3 evaluated the randomized controlled clinical trial comparing the impact of the interventions (aquatic exercise and education) on fall risk outcomes. Results: Older adults with hip OA reported a high frequency of falls and near-falls. The TUG, using a cut-off score of 10 sec., was associated with frequent near-fall history. There was a strong association of frequent near-falls to history of actual falls, with the association increasing 7-fold if lower falls-efficacy was present. Falls-efficacy was also an independent predictor of balance impairment. Screening for history of near-falls and falls-efficacy may be important in predicting risk of future falls. The combination of Aquatic Exercise and Education improved falls-efficacy and functional mobility compared to Aquatic Exercise only or no intervention. Aquatic Exercise on its own was not effective in decreasing fall risk factors or improving falls-efficacy. Significance of Findings: The accumulation of both physical and psychosocial risk factors in older adults with hip OA increases their vulnerability to falls and injury. Fall prevention programs for this population should be designed to include both exercise and education to address falls-efficacy and physical fall risk factors.