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ObjectiveTo describe systemic sclerosis (SSc) with myopathy in patients without classic SSc-specific and SSc-overlap autoantibodies (aAbs), referred to as seronegative scleromyositis.MethodsTwenty patients with seronegative scleromyositis diagnosed by expert opinion were analysed retrospectively for SSc features at myositis diagnosis and follow-up, and stratified based on HEp-2 nuclear patterns by indirect immunofluorescence (IIF) according to International Consensus of Autoantibody Patterns. Specificities were analysed by protein A−assisted immunoprecipitation. Myopathy was considered an organ involvement of SSc.ResultsSSc sine scleroderma was a frequent presentation (45%) at myositis diagnosis. Myositis was the most common first non-Raynaud manifestation of SSc (55%). Lower oesophagal dysmotility was present in 10 of 11 (91%) investigated patients. At follow-up, 80% of the patients met the American College of Rheumatology/EULAR SSc classification criteria. Two-thirds of patients had a positive HEp-2 IIF nuclear pattern (all with titers ≥1/320), defining three novel scleromyositis subsets. First, antinuclear antibody (ANA)-negative scleromyositis was associated with interstitial lung disease (ILD) and renal crisis. Second, a speckled pattern uncovered multiple rare SSc-specific aAbs. Third, the nuclear dots pattern was associated with aAbs to survival of motor neuron (SMN) complex and a novel scleromyositis subset characteriszed by calcinosis but infrequent ILD and renal crisis.ConclusionsSSc skin involvement is often absent in early seronegative scleromyositis. ANA positivity, Raynaud phenomenon, SSc-type capillaroscopy and/or lower oesophagal dysmotility may be clues for scleromyositis. Using HEp-2 IIF patterns, three novel clinicoserological subsets of scleromyositis emerged, notably (1) ANA-negative, (2) ANA-positive with a speckled pattern and (3) ANA-positive with nuclear dots and anti-SMN aAbs.

Autoimmune myositis encompasses various myositis-overlap syndromes, each being identified by the presence of serum marker autoantibodies. We describe a novel myositis-overlap syndrome in 4 patients characterized by the presence of a unique immunologic marker, autoantibodies to nuclear pore complexes. The clinical phenotype was characterized by prominent myositis in association with erosive, anti-CCP, and rheumatoid factor-positive arthritis, trigeminal neuralgia, mild interstitial lung disease, Raynaud phenomenon, and weight loss. The myositis was typically chronic, relapsing, and refractory to corticosteroids alone, but remitted with the addition of a second immunomodulating drug. There was no clinical or laboratory evidence for liver disease. The prognosis was good with 100% long-term survival (mean follow-up 19.5 yr). By indirect immunofluorescence on HEp-2 cells, sera from all 4 patients displayed a high titer of antinuclear autoantibodies (ANA) with a distinct punctate peripheral (rim) fluorescent pattern of the nuclear envelope characteristic of nuclear pore complexes. Reactivity with nuclear pore complexes was confirmed by immunoelectron microscopy. In a cohort of 100 French Canadian patients with autoimmune myositis, the nuclear pore complex fluorescent ANA pattern was restricted to these 4 patients (4%). It was not observed in sera from 393 adult patients with systemic sclerosis (n = 112), mixed connective tissue disease (n = 35), systemic lupus (n = 94), rheumatoid arthritis (n = 45), or other rheumatic diseases (n = 107), nor was it observed in 62 normal adults. Autoantibodies to nuclear pore complexes were predominantly of IgG isotype. No other IgG autoantibody markers for defined connective tissue diseases or overlap syndromes were present, indicating a selective and highly focused immune response. In 3 patients, anti-nuclear pore complex autoantibody titers varied in parallel with myositis activity, suggesting a pathogenic link to pathophysiology. The nuclear pore complex proteins, that is, nucleoporins (nup), recognized by these sera were heterogeneous and included Nup358/RanBP2 (n = 2 patients), Nup90 (n = 1), Nup62 (n = 1), and gp210 (n = 1). Taken together the data suggest that nup autoantigens themselves drive the anti-nup autoimmune response. Immunogenetically, the 4 patients shared the DQA1∗0501 allele associated with an increased risk for autoimmune myositis. In conclusion, we report an apparent novel subset of autoimmune myositis in our population of French Canadian patients with connective tissue diseases. This syndrome is recognized by the presence of a unique immunologic marker, autoantibodies to nuclear pore complexes that react with nups, consistent with an “anti-nup syndrome.”

Dermatomyositis (DM) is a major clinical subset of autoimmune myositis (AIM). The characteristic DM rash (Gottron papules, heliotrope rash) and perifascicular atrophy at skeletal muscle biopsy are regarded as specific features for this diagnosis. However, new concepts are challenging the current definition of DM. A modified Bohan and Peter classification of AIM was proposed in which the core concept was the inclusion of the diagnostic significance of overlap connective tissue disease features. In this clinical classification, a DM rash in association with myositis in the absence of overlap features indicates a diagnosis of pure DM. However, overlap features in association with myositis allow a diagnosis of overlap myositis (OM), irrespective of the presence or absence of the DM rash. Perifascicular atrophy may be present in both pure DM and OM. Recently, the presence of perifascicular atrophy in myositis without a DM rash was proposed as diagnostic of a novel entity, adermatopathic DM. We conducted the present study to evaluate these new concepts to further differentiate pure DM from OM. Using the modified Bohan and Peter classification, we performed a follow-up study of a longitudinal cohort of 100 consecutive adult French Canadian patients with AIM, including 44 patients with a DM phenotype, defined as a DM rash, and/or DM-type calcinosis, and/or the presence of perifascicular atrophy on muscle biopsy. A detailed evaluation was performed for overlap features, the extent and natural history of the DM rash, adermatopathic DM, DM-specific and overlap autoantibodies by protein A immunoprecipitation on coded serum samples, and associations with cancer and survival. Two distinct subsets were identified in patients with a DM phenotype: pure DM (n = 24) and OM with DM features, or OMDM (n = 20). In pure DM, the DM rash was a dominant finding. It was the first disease manifestation, was always present at the time of myositis diagnosis, and was associated with a high cutaneous score and chronicity. Concurrent heliotrope rash and Gottron papules (positive predictive value [PPV] 91%), as well as the V-sign and/or shawl sign (PPV 100%), were diagnostic of pure DM. Anti-Mi-2, anti-MJ, and anti-p155 autoantibodies were present in 50% of pure DM patients and were restricted to this subset (PPV 100%). Cancer was present in 21% of pure DM patients. The 15-year survival was excellent (92%). In contrast, in patients with OMDM, the first manifestation was proximal muscle weakness or other skeletal muscle-related complaints. The DM rash appeared at diagnosis or at follow-up, was associated with a low cutaneous extent score and was transient. Adermatopathic DM, which was absent in pure DM, was highly predictive (PPV 100%) of OMDM. Overlap autoantibodies (including anti-Jo-1, anti-PL-7, anti-PM-Scl, anti-U1RNP, and/or anti-U5-RNP) were found in 70% of OMDM patients. OMDM was not associated with cancer, but the 15-year survival was significantly decreased (65%). Perifascicular atrophy occurred as commonly in OMDM (n = 6/20, 30%) as in pure DM (n = 4/24, 17%) patients. These 6 OMDM patients had adermatopathic DM at myositis diagnosis, and only 1 of them developed a DM rash at follow-up, emphasizing the lack of specificity of perifascicular atrophy for pure DM. In conclusion, using the modified Bohan and Peter classification of AIM allowed identification of OMDM, a new clinical subset of OM. Furthermore, identification of OMDM allowed recognition of pure DM as a new entity that was distinct from OMDM or from OM without DM features. However, the absolute specificity of a DM rash and perifascicular muscle atrophy for the diagnosis of pure DM was lost. The distinctive clinical manifestations and autoantibody profiles presented are proposed as diagnostic criteria to differentiate pure DM from OMDM.

The neurological consequences following a traumatic brain injury (TBI) greatly affect the person's daily life as well as that of the supporting relatives who often feel powerless. The social integration of people suffering from TBI is a long-term situation. TBI often involves communication and behavioural disorders that become limitations to social participation. In general, interventions focus on reducing the individual's difficulties and do not consider strengthening their potential. Leisure, notably arts, has been found to assist in adapting to the loss of autonomy and enhancing social reintegration. This paper proposes a new approach focused on strengthening potential through artistic recreational activities as a medium for improving communication between a person with a TBI and his/her relative. A pre-experimental study was conducted with a group of dyads of persons with TBI and their significant other (n=5 dyads). Unexpected quantitative changes were found on the Perception of Relationship and Activ...

L’étude visait à identifier les représentations sociales de parents et d’enseignants à propos des compétences transversales, et à mettre en lumière les liens entre ces représentations et les actions éducatives et pédagogiques entreprises avec les adolescents. Les données ont été recueillies lors d’entretiens de groupes. Les résultats révèlent que les cinq parents et six enseignants ayant participé à l’étude ont des représentations sociales diversifiées au sujet des compétences transversales. Une meilleure compréhension du concept de compétences transversales et une meilleure communication entre ces deux groupes constituent des pistes prometteuses pour une plus grande cohésion dans les actions pédagogiques et éducatives menées auprès des adolescents., This study aims to describe parents’ and teachers’ social representations of cross-curricular competencies, and to clarify the links between those representations and the educative and pedagogical actions used with adolescents. Data were collected from focus groups. The results show that the 5 parents and the 6 teachers having participated in the study have diverse representations of cross-curricular competencies. A better understanding of the concept of cross-curricular competencies and a better communication between these two groups are promising avenues for greater cohesion in the educative and pedagogical actions with adolescents., Este estudio identifica las representaciones sociales de padres y de maestros acerca de las competencias transversales y pone de relieve las relaciones entre estas representaciones y las acciones educativas y pedagógicas emprendidas con adolescentes. Los datos fueron recolectados por medio de entrevistas de grupo. Los resultados muestran que los cinco padres y seis maestros que participaron al estudio tienen representaciones sociales diversificadas respecto a las competencias transversales. Una mejor comprensión del concepto de competencias transversales y una mejor comunicación entre estos dos grupos constituyen pistas prometedoras hacía una mejor cohesión de las acciones pedagógicas y educativas llevadas a cabo con adolescentes.

Objective To identify in patients with Raynaud's phenomenon (RP) independent markers that predict progression to definite systemic sclerosis (SSc) and to determine in patients with progression to SSc the type and sequence of microvascular damage and its relationship to SSc-specific autoantibodies. Methods Consecutive patients referred for evaluation of RP who had no definite connective tissue disease were evaluated for microvascular damage by nailfold capillary microscopy (NCM) and for anticentromere (anti–CENP-B), anti-Th/To, anti–topoisomerase I, and anti–RNA polymerase III (anti–RNAP III) autoantibodies by specific assays. Patients were studied prospectively. Results Of the 586 patients who were followed up for 3,197 person-years, 74 (12.6%) developed definite SSc. A characteristic sequence of microvascular damage was identified, starting with enlarged capillaries, followed by capillary loss, and then by capillary telangiectases. Definite SSc was diagnosed in close temporal relationship to capillary loss. Enlarged capillaries, capillary loss, and SSc-specific autoantibodies independently predicted definite SSc. Anti–CENP-B and anti-Th/To antibodies predicted enlarged capillaries; these autoantibodies and anti–RNAP III predicted capillary loss. Each autoantibody was associated with a distinct time course of microvascular damage. At followup, 79.5% of patients with 1 of these autoantibodies and abnormal findings on NCM at baseline had developed definite SSc. Patients with both baseline predictors were 60 times more likely to develop definite SSc. The data validated the proposed criteria for early SSc. Conclusion In RP evolving to definite SSc, microvascular damage is dynamic and sequential, while SSc-specific autoantibodies are associated with the course and type of capillary abnormalities. Abnormal findings on NCM at baseline together with an SSc-specific autoantibody indicate a very high probability of developing definite SSc, whereas their absence rules out this outcome.

Background:Toourknowledge,theburdenofdeepvenous thrombosis from the patient’s perspective has not been quantified. We evaluated health-related quality of life (QOL) after deep vein thrombosis and compared results with general population norms. Methods: This was a multicenter prospective cohort study of 359 consecutive eligible patients with deep vein thrombosisrecruitedat7Canadianhospitalcenters.Quality of life was assessed at baseline and at 1 and 4 months afterdiagnosisusinggeneric(36-ItemShort-FormHealth Survey) and disease-specific (Venous Insufficiency Epidemiological and Economic Study [VEINES]–QOL and VEINES symptom [VEINES-Sym] questionnaires) measures. Changes in QOL scores during the 4-month period were calculated, and determinants of lack of improvement in QOL were evaluated. Results: During the 4 months, mean 36-Item ShortFormHealthSurveyphysicalandmentalcomponentsummary scores improved by 5.1 and 4.6 points, respectively, and VEINES-QOL and VEINES-Sym scores improved by 3.1 and 2.2 points, respectively (P.001 fortimetrendforallmeasures).However,aboutonethird ofpatientshadworseningofQOLduringfollow-up.Multivariate analyses showed that worsening of the postthrombotic syndrome score was an independent predictor of worsening of 36-Item Short-Form Health Survey physical component summary (P=.04), VEINES-QOL (P.001), and VEINES-Sym (P.001) scores. The 36ItemShort-FormHealthSurveyphysicalcomponentsummary scores were lower than population norms at all points assessed. Conclusions: On average, QOL improves during the 4 months following deep vein thrombosis. However, in about one third of patients, QOL deteriorates, and at 4 months, average QOL remains poorer than population norms.Worseningofthepostthromboticsyndromescore is associated with worsening of QOL. Arch Intern Med. 2005;165:1173-1178

Abstract 566 Background and objectives: Deep venous thrombosis (DVT) is a common and serious vascular condition that is frequently complicated by the chronic post-thrombotic syndrome. Costs of DVT may occur over a long period and may be medical and non-medical in nature. During a Canadian multicenter cohort study of the long-term outcomes after DVT (The Venous Thrombosis Outcomes [VETO] Study), we prospectively quantified resource use and costs related to DVT during two years after DVT diagnosis, and identified clinical determinants of costs. Methods: The study population consisted of 355 consecutive patients diagnosed with objectively confirmed acute DVT at one of 7 participating hospitals in the province of Quebec, Canada. Using a societal perspective, we tracked total medical resource use (hospitalizations, physician visits, other health professional visits, medications, ambulance services, stockings, assistive devices) and non-medical resource use (loss of productivity, home care, transportation) incurred by DVT during the 2 years after diagnosis. Data sources included weekly patient-completed cost diaries, nurse-completed case report forms (baseline, 1, 4, 8, 12, 24 months and at any DVT-related clinical event) and the Quebec provincial administrative healthcare database (“RAMQ”). Resources for each patient were valued using individual patient level information obtained from RAMQ and patient diaries. Statistics Canada data, provincial health professionals associations and local suppliers were used to estimate resource costs if individual information was not available. The value of lost productivity was estimated using a friction-cost approach. Multivariate regression modeling for predictors of medical costs during 2 years included baseline demographic and clinical characteristics as well as the development of post-thrombotic syndrome (PTS) during study follow-up. Results: At study entry, mean age was 56.5 years, 50.1% were male, 2/3 were out-patients and 58.0% had proximal DVT. The mean duration of heparin and warfarin treatment was 7.6 days (SD 6.0) and 21.6 weeks (SD 10.0), respectively. During 2 years follow-up, the rate of DVT-related hospitalization was 3.5 per 100 patient-years (95% CI 2.2, 4.9). Patients reported, on average, 15.0 (SD 14.5) physician visits and 0.7 (SD 1.2) non-physician visits. Patients required 12.7 (SD 9.2) transportations, 38.6 (SD 138.0) hours of assistance and missed 12.1 (SD 39.8) workdays. The average per-patient total cost over 2 years was Can$4109 (95% CI $3658, $4561) with 63.7% of costs attributable to non-medical resource use. The two largest medical cost components were hospitalizations (Can$502; 95% CI $261, $744) and physician visits (Can$356; 95% CI $320, $392). More than two-thirds of all resource consumption occurred during the first 4 months after diagnosis. In multivariate analysis focusing on determinants of medical costs, concomitant pulmonary embolism (p = 0.002), idiopathic DVT (p= 0.003), and development of post-thrombotic syndrome during follow-up (p= 0.002) were independently associated with increased costs. Conclusion: The economic burden of DVT over the two years following initial diagnosis is substantial with almost two-thirds of costs attributable to non-medical resource use. Concomitant pulmonary embolism, idiopathic DVT, and development of PTS are important predictors of medical costs after DVT. Better adherence to thromboprophylaxis strategies and use of measures to prevent occurrence of PTS have the potential to diminish costs and resource utilization related to DVT. Disclosures: No relevant conflicts of interest to declare.

The reason some patients with deep venous thrombosis (DVT) develop the postthrombotic syndrome is not well understood.To determine the frequency, time course, and predictors of the postthrombotic syndrome after acute DVT.Prospective, multicenter cohort study.8 Canadian hospital centers.387 outpatients and inpatients who received an objective diagnosis of acute symptomatic DVT were recruited from 2001 to 2004.Standardized assessments for the postthrombotic syndrome using the Villalta scale at 1, 4, 8, 12, and 24 months after enrollment. Mean postthrombotic score and severity category at each interval was calculated. Predictors of postthrombotic score profiles over time since diagnosis of DVT were identified by using linear mixed modeling.At all study intervals, about 30% of patients had mild (score, 5 to 9), 10% had moderate (score, 10 to 14), and 3% had severe (score14 or ulcer) postthrombotic syndrome. Greater postthrombotic severity category at the 1-month visit strongly predicted higher mean postthrombotic scores throughout 24 months of follow-up (1.97, 5.03, and 7.00 increase in Villalta score for mild, moderate, and severe 1-month severity categories, respectively, vs. none; P0.001). Additional predictors of higher scores over time were venous thrombosis of the common femoral or iliac vein (2.23 increase in score vs. distal [calf] venous thrombosis; P0.001), higher body mass index (0.14 increase in score per kg/m(2); P0.001), previous ipsilateral venous thrombosis (1.78 increase in score; P = 0.001), older age (0.30 increase in score per 10-year age increase; P = 0.011), and female sex (0.79 increase in score; P = 0.020).Decisions to prescribe compression stockings were left to treating physicians rather than by protocol. Because international normalized ratio data were unavailable, the relationship between anticoagulation quality and Villalta scores could not be assessed.The postthrombotic syndrome occurs frequently after DVT. Patients with extensive DVT and those with more severe postthrombotic manifestations 1 month after DVT have poorer long-term outcomes.

Background and Objectives: It is not understood why some patients develop post thrombotic syndrome (PTS) after DVT while others recover without sequelae. We performed a prospective, multicenter study of long-term outcomes after DVT (the Venous Thrombosis Outcomes [VETO] Study) whose principal aim was to identify predictors of PTS. Methods: From 2001–2002, consecutive patients with objectively diagnosed DVT were recruited at 7 hospital centres. During study visits at Baseline, 1, 4, 8, 12 and 24 months, clinical data were collected, thrombophilia testing was performed and standardized assessments for PTS (using Villalta scale) were carried out by trained personnel. Patients were classified as having developed PTS if the ipsilateral Villalta score was ≥5 on at least 2 visits or at the final follow-up visit, and severe PTS if a score of >14 or a venous ulcer was documented on any one occasion. The influence of clinical, demographic, ergonomic and biological determinants on the risk of developing PTS was evaluated in bivariate and multivariate analyses. Results: 359 patients were recruited; 49% were male, mean age was 56 years, 2/3 were outpatients and 55% had proximal DVT. The cumulative risk of PTS was 37%, of which 1 in 6 cases was severe. Patients who developed PTS, compared with those who did not, were more likely to be older (p=.005), have had previous episode(s) of DVT (p=.0003), have atherosclerosis risk factors [hypertension (p=.0002), high cholesterol (p=.02)], higher BMI (p=0.0007), longer duration of symptoms before DVT diagnosis (p=.049) and work in a job with high physical demands (p=.05), and they were less likely to have the Prothrombin gene mutation (p=0.03). Variables of interest that did not influence the risk of PTS included: sex, location of DVT (proximal vs. distal), side of DVT (left vs. right), type of DVT (cancer-related, temporary risk factors [e.g. surgery, trauma] or idiopathic), initial anticoagulation with LMWH vs. UFH, duration of warfarin, Factor V Leiden mutation or prior ipsilateral musculoskeletal condition. In adjusted multivariate analyses, BMI (odds ratio [OR] 2.1 for BMI >30 vs. < 30, 95% confidence interval [CI] 1.1, 4.2), previous DVT (OR 2.6, 95% CI 1.4, 4.9) and hypertension (OR 1.9, 95% CI 1.04, 3.6) were independently associated with PTS. Conclusions: In our cohort, high BMI, previous history of DVT and hypertension were independent predictors of PTS, whereas presenting characteristics of the index DVT and its treatment did not influence the risk of developing PTS.

Background and Objectives: The post thrombotic syndrome (PTS) is a chronic complication of deep venous thrombosis (DVT). It is difficult to provide DVT patients with long-term prognostic information as there is little longitudinal data on the occurrence of PTS after DVT. We performed a prospective multicenter study of long-term outcomes after DVT (the Venous Thrombosis Outcomes [VETO] Study) to determine the incidence, timing of onset and severity of PTS. Methods: Consecutive patients with objectively diagnosed acute DVT were recruited at 7 participating hospital centres from April 2001-July 2002. Patients attended study visits at Baseline, 4, 8, 12 and 24 months. Clinical data were recorded and standardized assessments for PTS (using Villalta scale) were performed by trained study personnel at each follow-up visit. Patients were classified as having developed PTS if the ipsilateral Villalta score was ≥ 5 on at least 2 visits or at the final follow-up visit, and having severe PTS if a score of >14 or a venous ulcer was documented on any one occasion. The Kaplan-Meier survival method was used to estimate the cumulative probability of PTS and of severe PTS over time. Results: The study cohort consisted of 359 patients. The mean age was 56 years, 50% were male, 2/3 were outpatients, 55% had proximal DVT and 20% had previous DVT. The Kaplan-Meier estimates of cumulative risk of PTS were 29% at 4 months, 33% at 8 months, 35% at 12 months and 37% at 24 months. Corresponding risks of severe PTS were 6.6%, 6.9%, 6.9% and 6.9%, respectively. When the analysis was stratified according to history of DVT, the cumulative incidence of PTS in patients without previous DVT was 25%, 28%, 30% and 31% at 4, 8, 12 and 24 months. Corresponding rates of PTS in patients with previous DVT were 45%, 51%, 53% and 57%. Conclusions: More than one third of patients in our cohort developed PTS within 2 years of DVT, and of these, 1 in 6 was classified as severe. Most cases of PTS and of severe PTS were apparent by 4 months after DVT. Patients with previous DVT had a higher frequency of PTS and of late onset PTS. Our study provides longitudinal data on prognosis that is relevant both to patients with DVT and their treating physicians.

Objectives: To assess the validity and reliability of VEINES-QOL/Sym, a patient-reported questionnaire, for the evaluation of quality of life and symptoms in patients with deep venous thrombosis. Study design: Psychometric study within the Venous Thrombosis Outcomes (VETO) Study, a Canadian multicenter prospective cohort study of long term outcomes after venous thrombosis. Subjects: 359 English and French-speaking patients with deep vein thrombosis consecutively recruited at seven hospitals in the province of Quebec, Canada. Outcome measures: The 26-item VEINES-QOL/Sym is a patient-reported questionnaire that we originally developed and validated for use in patients with chronic venous disorders of the leg (J Vasc Surg 2003). VEINES-QOL/Sym generates separate summary scores for symptoms and quality of life. We performed a comprehensive psychometric evaluation of the acceptability, reliability, validity and responsiveness of VEINES-QOL/Sym in the VETO study population, all of whom had objectively diagnosed symptomatic deep venous thrombosis (mean age 56 years; 50% male; 67% outpatients; 55% proximal DVT). Results: Criterion-standard psychometric tests confirmed the acceptability (missing data, item endorsement frequencies, floor and ceiling effects), reliability (internal consistency, item-total and inter-item correlations, test-retest), validity (content, construct, convergent, discriminant, known groups) and responsiveness to clinical change of the VEINES-QOL/Sym. Conclusions: Our results indicate that VEINES-QOL/Sym is a practical, valid and reliable measure of quality of life and symptoms in patients with deep venous thrombosis. VEINES-QOL/Sym provides a rigorous tool to allow more comprehensive evaluation of patient outcomes in clinical trials and epidemiological studies of patients with deep venous thrombosis.