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To internally and externally validate our diagnostic criteria of early stage knee osteoarthritis (OA) in the CHECK and OAI cohorts. We applied two previously developed diagnostic models to all knees in CHECK and OAI cohorts to calculate probabilities of early stage knee OA at baseline. Knees were categorized into three groups based on probability: 'no OA' (probability ≤ 30%), 'uncertain' (probability between 30% and 70%) and 'early stage OA' (probability ≥ 70%). To validate the diagnosis, we obtained OA related outcome measures at 10-year follow-up in the CHECK cohort, and at 8-9-year follow-up in the OAI cohort. We compared outcome measures between 'no OA' and 'early stage OA' knees, and between 'no OA' and 'uncertain' knees using generalized estimating equations. In CHECK (n = 1042 knees) both models showed 'early stage OA' knees presented with significant and clinically relevant higher WOMAC scores, higher Kellgren & Lawrence (KL) grade, and higher rates of joint space narrowing (JSN) progression after 10 years, compared to 'no OA' knees. In OAI (n = 2937 knees) both models showed 'early stage OA' knees presented with significant and clinically relevant higher WOMAC scores, higher KL grade, and higher rates of KL and JSN progression after 8-9 years, compared to 'no OA' knees. Smaller, but still significant differences between 'uncertain' and 'no OA' knees were observed in both cohorts. These results support internal and external validity of the two sets of diagnostic criteria for early stage knee OA. [ABSTRACT FROM AUTHOR]

Abstract: Background: Neuroendocrine immunology in musculoskeletal diseases is an emerging scientific field. It deals with the aspects of efferent neuronal and neurohormonal bearing on the peripheral immune and musculoskeletal systems. This review aims to add new information that appeared since 2001. Search strategy: The following PubMed search sentence was used to find a total of 15,462 references between 2001 and March 2013: “(rheum⁎ OR SLE OR vasculitis) AND (nerve OR hormone OR neurotransmitter OR neuropeptide OR steroid).” In a continuous process, year by year, this search strategy yielded relevant papers that were screened and collected in a database, which build the platform of this review. Results: The main findings are the anti-inflammatory role of androgens, the loss of androgens (androgen drain), the bimodal role of estrogens (support B cells and inhibit macrophages and T cells), increased conversion of androgens to estrogens in inflammation (androgen drain), disturbances of the gonadal axis, inadequate amount of HPA axis hormones relative to inflammation (disproportion principle), biologics partly improve neuroendocrine axes, anti-corticotropin-releasing hormone therapies improve inflammation (antalarmin), bimodal role of the sympathetic nervous system (proinflammatory early, anti-inflammatory late—most probably due to catecholamine-producing local cells), anti-inflammatory role of alpha melanocyte-stimulating hormone, vasoactive intestinal peptide, and the Vagus nerve via α7 nicotinergic receptors. Circadian rhythms of hypothalamic origin are responsible for circadian rhythms of symptoms (neuroimmune link revealed). Important new pain-sensitizing immunological pathways were found in the last decade. Conclusions: The last decade brought much new information that gave birth to the first therapies of chronic inflammatory diseases on the basis of neuroendocrine immune targets. In addition, a new theory linked evolutionary medicine, neuroendocrine regulation of distribution of energy-rich fuels, and volume regulation that can explain many disease sequelae in patients with chronic inflammatory diseases. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The objective is to determine the relationship between clinical features and non-Hodgkin lymphoma (NHL) development in primary Sjögren's Syndrome (pSS), taking recently designed disease activity/severity scores into account. Methods: Medical charts of pSS patients were retrospectively analyzed, scoring first and last visits with the (cumulative) EULAR Sjögren's Syndrome Disease Activity Index and counting extraglandular manifestations, comparing patients with and without NHL. Results: One hundred ninety-five patients were analyzed with a median follow-up of 92 months (range 12–256). Twenty-one patients (11%) had NHL. Associations of parotid gland enlargement (OR 2.84) and low C4 (OR 7.71) with NHL were confirmed. In NHL patients, development of purpura, peripheral neuropathy (PNP), and glomerulonephritis (GN) concurred with lymphoma in 3/3, 5/7, and 2/2 of cases, respectively. Otherwise, purpura and PNP were not associated with NHL later on. This suggests that these symptoms might represent paraneoplastic events (in 16%, 24%, and 100% of our cases, respectively). Presence of IgM-kappa clonal components was associated with lymphoma in 64% of cases. Disease activity/severity scores at first visit could not predict lymphoma development, nor was the pSS disease course significantly worse in patients with NHL. Conclusions: In our cohort, no clinical manifestation or disease score could clearly select patients with subsequent lymphoma development. Presence of IgM-kappa clonal components and development of purpura, PNP, and GN should alert the clinician for the presence of lymphoma. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether the presence of germinal centers (GCs) in salivary glands of patients with primary Sjögren''s syndrome (pSS) is related to the severity of disease course and distinct immunopathology features. Methods: A systematic search was performed in September 2011 for terms and synonyms of Sjögren''s syndrome and germinal centers. A total of 80 articles were retrieved, of which 16 were included for (meta-) analysis. Results: GC morphology was present in a mean ± SD 25.1 ± 5.0% of pSS patients. Mean lymphocyte focus scores were 1.25 points higher in patients with GCs as compared to those without GCs. Saliva production was reduced in patients with GCs, although this did not reach statistical significance. Percentages of patients positive for rheumatoid factor, anti-Sjögren''s syndrome A (SSA), and anti-Sjögren''s syndrome B (SSB) antibodies were significantly higher in patients with GCs (mean increase, 15%, 18%, and 18%, respectively). Additionally, patients with GCs were characterized by enhanced levels of local and systemic proinflammatory mediators. Importantly, these patients have a higher risk of lymphoma development (14% versus 1%). Conclusions: Patients with GCs are characterized by more severe disease, although the small number of studies and their design hamper generalizability of results. The precise mechanisms that contribute to the development and persistence of germinal centers in pSS are largely unknown. This and the strongly increased risk of lymphoma development warrant intensive studies for the role of germinal centers in the immunopathology of pSS. [ABSTRACT FROM AUTHOR]

The 2nd International Conference on the Neuroendocrine Immune Basis of the Rheumatic Diseases was held in Genova, Italy from 21–23 September 2001. [Copyright &y& Elsevier]

• Aucun facteur prédictif n'a été jugé suffisamment fiable pour prédire la réponse clinique au méthotrexate 3 à 6 mois suivant le début du traitement chez les patients individuels. • Le sexe féminin, le tabagisme et la positivité du facteur rhumatoïde apparaissait comme étant des facteurs prédictifs individuels peu robustes de non réponse dans plusieurs études mais ces résultats n'ont pas été retrouvés dans toutes les études. • Un modèle épigénétique validé intéressant a été trouvé et nécessite une validation supplémentaire. Identifier, par une revue systématique de la littérature, les facteurs prédictifs de réponse clinique au méthotrexate chez des patients atteints de polyarthrite rhumatoïde, afin de faciliter la mise en place d'un traitement personnalisé. Les bases de données PubMed et Embase ont été consultées pour la sélection des articles originaux. Les abstracts des rencontres annuelles de l'EULAR (European League Against Rheumatism) et de l'ACR (American College of Rheumatology) de ces deux dernières années ont également été examinés. Ont été inclus les articles décrivant les facteurs prédictifs de la réponse clinique au méthotrexate 3 à 6 mois suivant le début du traitement, période qui permet de déterminer l'efficacité du traitement et d'envisager une adaptation thérapeutique selon les recommandations treat-to-target. 30 articles ont été inclus, contenant un total de 102 facteurs prédictifs différents et 11 modèles prédictifs. 19 facteurs et 2 modèles prédictifs ont été évalués au sein de plusieurs cohortes. Le sexe féminin est apparu comme étant un facteur prédictif de non-réponse au cours de deux études (odds ratios 0,55 et 0,54) mais ces observations n'ont pas été retrouvées dans deux autres études. Dans deux études, le tabagisme permettait de prédire la non-réponse (odds ratios ajustés 0,35 et 0,60) mais ce résultat apparaissait contradictoire pour tous les critères de réponse évalués. La positivité du facteur rhumatoïde était un marqueur prédictif de non réponse dans deux études (hazard ratio ajusté 0,61, odds ratio ajusté 0,4) mais cette observation n'a pas été retrouvée dans trois autres études. L'hétérogénéité des études n'a pas permis de comparer les valeurs prédictives entre les études. Par ailleurs, un modèle épigénétique validé a été retrouvé (aire sous la courbe 0,90 et 0,91). Aucun des facteurs ne permettait de prédire de manière fiable la réponse clinique au méthotrexate après 3 à 6 mois de traitement chez les patients : ces facteurs affichaient un faible pouvoir de prédiction. Cependant, un modèle épigénétique prometteur a été trouvé et reste à valider. [ABSTRACT FROM AUTHOR]

Objectives: To identify, by a systematic literature review, predictors of clinical response to methotrexate treatment in rheumatoid arthritis patients, which would facilitate personalised treatment.Methods: PubMed and Embase databases were searched for original articles. Additionally, congress abstracts of European League Against Rheumatism and American College of Rheumatology annual meetings of the past 2 years were screened. Articles describing predictors of clinical response to methotrexate after 3 to 6 months were included, since this reflects the time span used to determine treatment effectiveness and decide on treatment changes in treat-to-target recommendations.Results: Thirty articles were included, containing 100 different predictors and 11 predictive models. Nineteen predictors and 2 predictive models were studied in multiple cohorts. Female gender was found to be a predictor of non-response in two studies (odds ratios 0.55 and 0.54), but these findings could not be replicated in two other studies. In two studies, smoking predicted non-response (adjusted odds ratios 0.35 and 0.60), although this was inconsistent over all response criteria assessed. Rheumatoid factor positivity predicted non-response in two studies (adjusted hazard ratio 0.61, adjusted odds ratio 0.4), but this was not found in three other studies. Heterogeneity in studies prohibited further comparison of predictive values between studies. Additionally, a validated epigenetic model was found (area under the curve 0.90 and 0.91).Conclusions: No predictors were identified reliably predicting clinical response to methotrexate after 3 to 6 months in the individual patient: clinical predictors were weak. However, a promising epigenetic model was found that needs further validation. [ABSTRACT FROM AUTHOR]

In this manuscript, presented as a Reflective Practice, the learning experiences and reflections of a healthcare team on redeveloping the transitional care for young adults with a juvenile rheumatic disease are described. In this process of redeveloping care, the healthcare team experienced that small step, driven by patient stories and involvement of patients in all phases from development to evaluation, led to meaningful results. The eHealth interventions, developed to support the transition and to increase self-management were found to be feasible and evaluated positively by the young adult group. But the healthcare team also experienced that the focus on the patient alone, is not enough to implement self-management interventions and sustain patient centered care in daily practice. How healthcare professionals personally think and feel about patient centered care is essential and needs to be discussed in daily care.It determines the way of being present with attention and commitment in daily health care. It affects the hands, head and heart. A daily reflection on shared answers of the patient and the health care professional to the question 'what is the most important to you?'may help to implement patient centered care in health practice. [ABSTRACT FROM AUTHOR]

Objective: Aim of this study was to investigate preferences and needs regarding the structure and content of a person-centered online self-management support intervention for patients with a rheumatic disease.Methods: A four step procedure, consisting of online focus group interviews, consensus meetings with patient representatives, card sorting task and hierarchical cluster analysis was used to identify the preferences and needs.Results: Preferences concerning the structure involved 1) suitability to individual needs and questions, 2) fit to the life stage 3) creating the opportunity to share experiences, be in contact with others, 4) have an expert patient as trainer, 5) allow for doing the training at one's own pace and 6) offer a brief intervention. Hierarchical cluster analysis of 55 content needs comprised eleven clusters: 1) treatment knowledge, 2) societal procedures, 3) physical activity, 4) psychological distress, 5) self-efficacy, 6) provider, 7) fluctuations, 8) dealing with rheumatic disease, 9) communication, 10) intimate relationship, and 11) having children.Conclusion: A comprehensive assessment of preferences and needs in patients with a rheumatic disease is expected to contribute to motivation, adherence to and outcome of self-management-support programs.Practice Implications: The overview of preferences and needs can be used to build an online-line self-management intervention. [ABSTRACT FROM AUTHOR]

Background Data on recent trends in mortality after hip fracture are scarce. Aims were therefore to examine secular trends in all-cause and cause-specific mortality post hip fracture and to compare this to the general population from 2000 to 2010. Methods Population-based cohort study within the United Kingdom Clinical Practice Research Datalink and linked to cause of death data for 57.7% of patients. Patients with a first hip fracture (n = 31,495) were matched to up to four controls by age, sex, index date, and practice. All subjects were followed for death, and lifestyle, disease and medication history adjusted hazard ratios (HRs) were calculated. Results One-year all-cause mortality after hip fracture declined from 2009 and was 14% lower after, compared with before 2009 (22.3% to 20.5%, adj. HR 0.86, 95% CI: 0.81–0.92). The decline was observed for males (≥ 75 years) and females (≥ 85 years). Significant contributors to the decline in mortality post hip fracture were respiratory infections in females as were malignant diseases in males. However, one-year all-cause mortality remained unaltered over the decade when compared to controls with a 3.5-fold and 2.4-fold increased risk in males and females respectively. No significant changes were observed in the relative risks for one-year cause-specific mortality for both genders. Conclusions One-year mortality after hip fracture has declined over the last decade in the UK. However, the difference in one-year mortality between hip fracture patients and the general population remained unaltered. These observations highlight the need for the continued implementation of evidence-based standards for good hip fracture care. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Individuals differ in their style of processing emotions (e.g., experiencing affects intensely or being alexithymic) and their strategy of regulating emotions (e.g., expressing or reappraising). A match–mismatch model of emotion processing styles and emotion regulation strategies is proposed and tested. This model specifies that for people high on affect intensity, emotion expression is more adaptive than reappraisal, whereas for alexithymic people, reappraisal is more adaptive than expression. The present study tested this model in 403 women with fibromyalgia (mean age 46.5±12.3years). Methods: In a cross-sectional design, we assessed affect intensity (Berkeley Expressivity Questionnaire), alexithymia (Toronto Alexithymia Scale-20), cognitive reappraisal (Emotion Regulation Questionnaire), and emotion expression (Emotional Approach Coping Scales), as well as the impact of fibromyalgia (Fibromyalgia Impact Questionnaire). Results: Multiple regression analyses with interaction terms indicated that among people high on affect intensity, emotion expression – but not cognitive reappraisal – was associated with less fibromyalgia impact. No support was found for the hypothesis that among alexithymic people, cognitive reappraisal would be more adaptive than emotion expression. Conclusion: Findings suggest that for women with fibromyalgia who experience their emotions intensely, an emotional disclosure or expression intervention may be beneficial. This hypothesis requires verification in experimental studies. [Copyright &y& Elsevier]

Abstract: Objective: Disturbances in emotional functioning may contribute to psychological and physical symptoms in patients with fibromyalgia. This study examined emotions and emotion-regulation strategies in women with fibromyalgia and in controls, and how these variables relate to symptoms of fibromyalgia. Methods: We compared 403 women with fibromyalgia to 196 control women using self-report questionnaires. Results: Negative emotions and the use of emotional-avoidance strategies were elevated, and positive emotions were reduced, in fibromyalgia patients; the alexithymia scale “difficulty identifying feelings” showed a large deviation from normal. Emotional-approach measures were not deviant. In the fibromyalgia sample, emotional-avoidance strategies were highly correlated with more mental distress and were modestly correlated with more pain and fatigue, while emotional-approach strategies were only minimally related to better functioning. We tested two interaction models. The intense experiencing of emotions was related to more pain only in patients who lack the ability to process or describe emotions. Although fibromyalgia patients showed deficits in the experiencing of positive affect, positive affect did not buffer the association between pain and negative affect. Conclusion: This study demonstrates increased negative emotions and decreased positive emotions, as well as increased emotional-avoidance strategies, in women with fibromyalgia. Research should test whether interventions that reduce emotional avoidance lead to health improvements in women with fibromyalgia. [Copyright &y& Elsevier]

Abstract: Objective: Emotional engagement, cognitive restructuring, and positive future directedness are considered core elements to induce change in emotional disclosure interventions. Our aim was to examine the induction of these elements and the feasibility of an emotional disclosure intervention adapted for home application. Methods: The intervention emphasized expression of negative and positive emotions (session 1–4), search for meaning (session 3), and a positive future-oriented ending (session 4). A randomized clinical trial in patients with rheumatoid arthritis compared the adapted intervention (n =40) with a time management control condition (n =28). Feasibility was evaluated regarding adherence, compliance with instructions, perceived viability, and clinical safety. Induction of core elements was evaluated by analysis of change in immediate affective responses and by computerized text analysis of word use. Results: Feasibility criteria were successfully met. The disclosure condition produced higher immediate negative affect and use of emotion, insight, and optimism words compared to control, and induced the elements of change within sessions as intended. Conclusion: The adapted intervention is feasible for home application and induces change in variables that indicate emotional engagement, cognitive restructuring, and positive future directedness. Practice implications: Empirical support of health benefits of this emotional disclosure intervention will extend its applicability in patient self-care. [Copyright &y& Elsevier]

Abstract: The suppressive effects of CD4+CD25+ regulatory T cells (Tregs) on T cells have been well documented. Here we investigated whether human CD4+CD25+ Tregs can inhibit the proinflammatory properties of monocytes/macrophages. Monocytes and T cells were isolated from peripheral blood of healthy volunteers by magnetic cell separation and cocultured for 40 h. Monocytes were analyzed directly for cytokine production and phenotypic changes or repurified and used in T-cell stimulation and lipopolysaccharide challenge assays. Coculture with CD4+CD25+ Tregs induced minimal cytokine production in monocytes, whereas coculture with CD4+CD25− T cells resulted in large amounts of proinflammatory (tumor necrosis factor-α, interferon-γ, interleukin-6) and regulatory (interleukin-10) cytokines. Importantly, when these CD4+CD25+ Treg-treated monocytes were repurified after coculture and challenged with lipopolysaccharide, they were severely inhibited in their capacity to produce tumor necrosis factor-α and interleukin-6 compared with control-treated monocytes. In addition, monocytes that were precultured with CD4+CD25+ Tregs displayed limited upregulation of human leukocyte antigen class II, CD40 and CD80, and downregulation of CD86 compared with control-treated monocytes. This altered phenotype had functional consequences, as shown by the reduction in T cell-stimulatory capacity of Treg-treated monocytes. Together, these data demonstrate that CD4+CD25+ Tregs can exert direct suppressive effects on monocytes/macrophages, thereby affecting subsequent innate and adaptive immune responses. [Copyright &y& Elsevier]

The focus of our studies was to determine whether the antipolymer antibody assay (APA) as an objective laboratory assay could contribute to the diagnosis in women with a silicone breast implant (SBI) and complaints/symptomatic disease. We investigated whether a population of symptomatic SBI recipients exists with a high prevalence of APA in the Netherlands. The study participants were selected based on self-reported complaints. In one study their physician was approached for additional information on their disease status. Two groups of 42 women were included in the studies, with a mean SBI exposure of 17 and 16 years, respectively. The participants were clinically examined, and the APA level in serum samples determined. The study population of SBI recipients was categorised in severity subgroups based on the functional capacity, and the study physicians general assessment of pain and disease activity. Positive APA levels were found in 10% of the SBI recipients. Also in control groups 8% showed a positive APA response. After categorisation most (65 of 84) SBI recipients belonged to the limited severity subgroup on an increasing scale of limited, mild, moderate and advanced. Eight were categorised in the mild, four in the moderate, and seven in the advanced severity subgroup. None of the APA positive women were found to belong to the moderate or advanced severity subgroup. Seven of the APA positive women belonged to the limited, and one woman to the mild severity subgroup. In conclusion, we were unable to include a large proportion of severely symptomatic SBI recipients in our study populations. So, we cannot confirm the results of Tenenbaum et al. [1] on the presence of APA in symptomatic SBI recipients. However, our failure in two separate studies to recruit symptomatic SBI recipients suggests that the population of severely symptomatic SBI recipients in the Netherlands is rather small. The number of APA positive responses in our study population was low. In addition, also in the normal population a similar low percentage of positively reacting women were observed. Hence, we cannot recommend the use of the APA assay for diagnostic purposes in the clinical evaluation of SBI recipients with severe complaints/symptoms. [Copyright &y& Elsevier]

Pain-related avoidance factors and social resources, as assessed by pain coping and social support, are supposed to have lasting effects on functional disability and pain in chronic pain disorders. As a follow-up to a prospective study demonstrating short-term effects after one year (Behaviour Research and Therapy, 36, 179–193, 1998), the role of pain coping and social support at the time of diagnosis was investigated in relationship to the long-term course of functional disability and pain after three and five years in 78 patients with rheumatoid arthritis (RA), taking into account personality characteristics of neuroticism and extraversion, clinical status and use of medication. In line with findings at the one-year follow-up, results showed that more passive pain coping predicted functional disability at the three-year, but not the five-year follow-up. In addition, low levels of social support at the time of diagnosis consistently predicted both functional disability and pain at the three and five-year follow-ups. Results indicate that pain coping and social support, assessed very early in the disease process, can affect long-term functional disability and pain in RA, and suggest that early interventions focusing on pain-related avoidance factors and social resources for patients at risk may beneficially influence long-term outcomes in RA. [Copyright &y& Elsevier]

Objective: Stress-vulnerability factors were studied for their ability to predict long-term disease activity in early rheumatoid arthritis.Methods: In a prospective study involving 78 recently diagnosed rheumatoid arthritis (RA) patients, the role of personality characteristics (neuroticism, extraversion), physical and psychological stressors (chronic, disease-related stressors of functional disability, pain, disease impact on daily life, as well as major life events), coping and social support at the time of diagnosis was examined to predict changes in clinical indicators of disease activity 1, 3 and 5 years later.Results: While stress-vulnerability factors failed to predict disease activity at the 1-year follow-up, disease activity at the 3- and 5-year follow-ups was predicted by coping and social support at the time of diagnosis, after adjusting for disease activity at first assessment, other biomedical and psychosocial factors and use of medication. Low levels of social support predicted increased disease activity at the 3-year follow-up, and high avoidance coping predicted increased disease activity at the 3- and 5-year follow-ups.Conclusion: Findings indicate the potential prognostic value of avoidance coping and social support for the long-term course of disease activity in early RA and suggest that the effects of these vulnerability factors predominantly operate in the long term. [ABSTRACT FROM AUTHOR]