Purpose: To characterize muscle recovery following total hip arthroplasty (THA) combining genetic adaptations in the affected leg with objective function and body composition assessment. Methods: Preoperatively and at six weeks postoperatively, objective function was assessed by: maximal voluntary contraction of the operated leg quadriceps (MVCOLQ) in Newtons (N), 30[Formula: see text]s chair sit-to-stand (ST), and six-minute walk test (6MWT), with lean mass of the operated leg estimated by dual energy X-ray absorptiometry (DEXA). Genetic adaptations were assessed from vastus lateralis (VL) biopsies by quantitative polymerase chain reaction (qPCR) analysis of markers of hypertrophy (FOS, calpain2 (CAPN2)), atrophy (20[Formula: see text]s proteasome alpha subunit 7 (PSMA7), cathepsin L2 (CTSL2), inflammation (Tumour necrosis factor alpha (TNF-[Formula: see text]), Interleukin-6 (IL-6)) and lipid metabolism (lipoprotein lipase, LPL and peroxisome proliferated activated receptor gamma (PPARAG). Results: 14 patients were recruited. At six weeks, no significant differences, relative to preoperative values, were noted in either objective function or leg lean mass. Markers for hypertrophy were increased (FOS [Formula: see text]1463%, [Formula: see text]), with atrophy (PSMA7 [Formula: see text]44.8%, [Formula: see text]; CTSL2 [Formula: see text]42.5%, [Formula: see text]), inflammation (TNF [Formula: see text]29.6%, [Formula: see text]) and lipid metabolism markers showing a decreasing trend (LPL [Formula: see text]42.45%, [Formula: see text]). Conclusion: The initial post-THA intramuscular environment appears supportive of anabolism. However, this is not reflected in objective function or lean mass measures at six weeks, suggesting longer duration may be required for physiological adaptation to occur.
Objective Anti-C1q has been associated with systemic lupus erythematosus (SLE) and lupus nephritis in previous studies. We studied anti-C1q specificity for SLE (vs rheumatic disease controls) and the association with SLE manifestations in an international multicenter study. Methods Information and blood samples were obtained in a cross-sectional study from patients with SLE ( n = 308) and other rheumatologic diseases ( n = 389) from 25 clinical sites (84% female, 68% Caucasian, 17% African descent, 8% Asian, 7% other). IgG anti-C1q against the collagen-like region was measured by ELISA. Results Prevalence of anti-C1q was 28% (86/308) in patients with SLE and 13% (49/389) in controls (OR = 2.7, 95% CI: 1.8–4, p < 0.001). Anti-C1q was associated with proteinuria (OR = 3.0, 95% CI: 1.7–5.1, p < 0.001), red cell casts (OR = 2.6, 95% CI: 1.2–5.4, p = 0.015), anti-dsDNA (OR = 3.4, 95% CI: 1.9–6.1, p < 0.001) and anti-Smith (OR = 2.8, 95% CI: 1.5–5.0, p = 0.01). Anti-C1q was independently associated with renal involvement after adjustment for demographics, ANA, anti-dsDNA and low complement (OR = 2.3, 95% CI: 1.3–4.2, p < 0.01). Simultaneously positive anti-C1q, anti-dsDNA and low complement was strongly associated with renal involvement (OR = 14.9, 95% CI: 5.8–38.4, p < 0.01). Conclusions Anti-C1q was more common in patients with SLE and those of Asian race/ethnicity. We confirmed a significant association of anti-C1q with renal involvement, independent of demographics and other serologies. Anti-C1q in combination with anti-dsDNA and low complement was the strongest serological association with renal involvement. These data support the usefulness of anti-C1q in SLE, especially in lupus nephritis.
Objective The Medical Outcomes Study Short Form 36 (SF‐36) is recommended to assess quality of life (QOL) in systemic lupus erythematosus (SLE). The aim of the current study was to assess QOL over time in the first 5 years of a multicenter inception cohort of patients with SLE. Methods An inception SLE cohort was assembled according to a standardized protocol between 2000 and 2012. In addition to clinical and laboratory assessments, patients completed the SF‐36 at yearly intervals. Only patients who had ≥5 completed QOL questionnaires were included in these analyses. Generalized estimating equation models were run separately for each of the 8 subscales and for the physical and mental component summary scores, adjusting for repeated measures by patients. Results A total of 495 patients were included. The mean ± SD disease duration at the first visit was 5.3 ± 4.1 months. The mean ± SD age at enrollment was 35.8 ± 13.2 years. All 8 subscales and the 2 summary scores showed improvement in the first 2 years from enrollment. Between years 2 and 5, none of the subscales or summary scores showed any change. Minimum clinically important improvement was achieved by 35–56% of the patients and was influenced by demographic and disease factors. Conclusion Unlike late‐stage lupus, where QOL is stable over time, in patients with early disease, all subscales improve in early followup up to 2 years. Therefore, the SF‐36 may be a sensitive outcome measure in early disease in patients with SLE.
Background: Children and young adults with JIA have increased levels of poor oral hygiene and dental decay [1].Periodontitis and types of arthritis are linked by similar components of blood cytokine profiles.Good dental health can be directly affected in JIA patients due to physical limitations in upper limb movements making brushing and flossing teeth difficult.An important factor in oral care is good dental hygiene and access to dental health practitioners.NHS advice is that all children should be reviewed by a dentist annually and be offered both sealant of their teeth and fluoride varnish at the appropriate time.Our aim was to establish if our patients had any barriers to accessing dental care.Methods: All patients (age 18 and under) diagnosed with JIA in the paediatric rheumatology clinic over a period of 3 months were asked to complete a dental care questionnaire.Parents completed the questionnaire for their children if necessary.Data were analysed using Excel.Results: 30 questionnaires were completed.Demographics were M:F 1:1.3, all children were diagnosed with JIA, average age 10.5 years with range 2-18.27 children were registered with an NHS dentist with the exception of one child with a private dentist.26 children had seen a dentist at least annually and one child in the past 2 years. 2 children, one aged 16, were not registered with a dentist because their parents didn't think it was important.11 children had 25 fillings in total, 9 of these children were not supervised during dental hygiene.13 children admitted to drinking sugary drinks daily and had 16 dental fillings.None of the children admitted to smoking.Conclusions: Whilst our audit showed that most children were registered with a dentist and were reviewed annually, only 1 child had been offered sealant and fluoride varnish.The NHS advises that children with chronic medical conditions can be seen either by their NHS dentist or by the local Community specialist dental service which can be accessed by referral from their rheumatology department or NHS dentist.None of the children were seen by the specialist dental service.We have developed an information leaflet informing parents and children with JIA of the importance of dental health explaining the benefits of both sealant and fluoride for teeth.
Historically immunology was considered to be the science of self–non-self discrimination and inflammation against self was invariably considered in relationship to B and T cell tolerance failure. Indeed the classical autoantibody associated autoimmunity paradigm, that sometimes powerfully manifests as fulminant lupus-related thrombosis, for example, attests to the veracity of the autoimmunity concept that underpins much of rheumatology practice. However, non-infectious inflammation against self was suspected not to be exclusively within the realms of autoimmunity, but until recently a clearly defined concept of what exactly this represented did not exist. The teaching of immunology commences with the fact that the immune system is composed of an innate and an adaptive arm and that these are ultimately functionally integrated. Over a decade ago the word autoinflammation was used to describe rare monogenic disorders including familial mediterranean fever (FMF) and TNF-associated peroidic fever syndrome (TRAPS) where the inflammation was not onstensibly linked to autoimmunity. Recognizing that perturbation of immune responses could equally be dependent on aberrant innate immunity we defined autoinflammmation as the diametric opposite boundary to autoimmunity where disease is driven by intrinsic perturbation of the non-immune cells of the target tissues or the innate immune populations that patrol these sites [1]. The innate immune-dependent or autoinflammatory disorders have clinical phenotypes distinct from those of autoimmunity and at the molecular level often converge on key cytokines such as IL-1 or TNF. The purpose of this talk is to show how autoinflammation can be recognized based on clinical features, serology and genetics. It also shows how diseases that were formerly designated as autoimmune may in some cases be autoinflammatory at disease inception. Diseases that are intermediate between autoinflammation and autoimmunity will be briefly touched on. The proper clinical designate of autoinflammation is key for treatment strategies. Thus far, many of the autoinflammatory diseases have shown a remarkable response to strategies of IL-1 antagonism. Illustrative cases including those where a clear diagnosis was not initially evident will be used to show treatment strategies. Disclosures: Reference 1. McGonagle D, McDermott MF. A proposed classification of the immunological diseases. PLoS Med 2006;3:e297.
Background: Control cognitions have been directly related to positive engagement with rehabilitation regimes. The impact of such cognitions on recovery following surgery is not well understood. Purpose: To assess whether perceived control cognitions predict function 9-12 months following total hip replacement (THR). Methods: Prospective cohort study performed as part of a randomised controlled trial. Behavioural cognitions (BC) (recovery locus of control (RLOC); perceived external behavioural control (PEBC))) and subjective functional outcome measures (Oxford hip score (OHS) and a reduced version of the Western Ontario and McMasters University Osteoarthritis Function scale (rWOMAC PF)) were administered pre-operatively and up to 12 months post-operatively to 50 patients randomised to home-based progressive resistance training (N = 26) or standard rehabilitation (N = 24), post-THR. Regression analysis investigated variance in functional scores. Results: Group randomisation had no effect on BC. RLOC and OHS (6 months) correlated significantly with 12-month OHS, with 6-month OHS predicting 62.3% of the variance in 12-month OHS. 12-month rWOMAC PF was determined by each of its three previous assessments (pre-operative 8.8%, 6 weeks 17.8% and 6 months 67.3%). Variance in functional gain at 12 months (OHS and rWOMAC PF) was explained by pre-operative OHS and rWOMAC PF (63.7% and 63.8%, respectively). Conclusions: BC had no impact on functional outcome in this population. Subjectively assessed function at 12 months, as well as the levels of functional gain over time, was best explained by the patients' earlier functional status.
To derive a mapping algorithm to estimate scores (utility values) for the preference-based SF-6D measures from the non-preference-based disease-specific LupusQoL. A total of 282 systemic lupus erythematosus (SLE) patients completed the LupusQoL and SF-6D at the same assessment. Models of the relationship between them were estimated using OLS regression. The SF-6D utility score was modelled using total scores on the 8 LupusQoL domains, employing a backward inclusion procedure. Model performance was judged using the root mean squared error (RMSE) and range of predicted values. The mean (SD) age of the sample was 45 (13.4) years and the mean (SD) SF-6D score was 0.61 (0.13). The mean scores for the LupusQoL domains ranged from 52.5 (Fatigue) to 73.5 (Body Image). Four of the eight LupusQoL domains were selected for inclusion in the final model (Physical Health, Pain, Emotional Health, Fatigue) because these domains were measured in both instruments. The root mean square error (RMSE) for the mapping function was 0.0701, lower than that reported for many published mapping functions. The overall model fit was good (R2=0.7155), although some under prediction at the upper end of the SF-6D was observed. There appears to be a strong relationship between the LupusQoL and SF-6D. Prediction errors are lower than for many published mapping functions, signifying that the mapping algorithm developed here provides a methodology for predicting SF-6D utility values from LupusQoL data. Potentially this could reduce patient burden if all of the necessary information can be obtain from administering the LupusQoL alone. However, the omission of disease-specific LupusQoL domains (intimate relationships, body image, burden to others, planning) from the final model, raises concerns that the specificity for SLE may be lost in this algorithm. Further out of sample testing will be useful to confirm the performance of this algorithm.
Objective. To examine the accumulation of risk factors over 3 years in a multicenter, international inception cohort of patients with systemic lupus erythematosus (SLE).Methods. The Systemic Lupus International Collaborating Clinics registry for atherosclerosis comprises 27 centers from 11 countries. An inception cohort of 935 patients with SLE was assembled, according to a standardized protocol, from 2000 to 2006 to study risk factors for atherosclerosis. Both classic and other coronary artery disease (CAD) risk factors were collected at entry and through 3 years of followup. Therapy was documented over the 3 years. The Framingham 10-year risk factor profile was calculated for each patient at year 1 and year 3.Results. A total of 278 patients from the inception cohort were followed for 3 years and constituted the population for this study. At enrollment a substantial number of patients already demonstrated several risk factors for CAD, both classic and other. All risk factors increased from enrollment over the 3 years of followup. Treatment of hypertension and hypercholesterolemia also increased over 3 years, but less so for hypercholesterolemia. The Framingham 10-year CAD risk profile was higher in men than in women both at entry and at 3 years, and remained unchanged over the 3 years. Corticosteroid use increased only slightly over 3 years, but use of antimalarials and immunosuppressive agents increased to a greater extent.Conclusion. Patients with SLE should be monitored for CAD risk factors from the time of diagnosis and appropriate treatment should be instituted early.
Objective: To assess the reliability of Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2000 index in routine practice and its ability to capture disease activity as compared with the British Isles Lupus Assessment Group (BILAG)-2004 index. Methods: Patients with systemic lupus erythematosus from 11 centres were assessed separately by two raters in routine practice. Disease activity was assessed using the BILAG-2004 and SLEDAI-2000 indices. The level of agreement for items was used to assess the reliability of SLEDAI-2000. The ability to detect disease activity was assessed by determining the number of patients with a high activity on BILAG-2004 (overall score A or B) but low SLEDAI-2000 score (<6) and number of patients with low activity on BILAG-2004 (overall score C, D or E) but high SLEDAI-2000 score (⩾6). Treatment of these patients was analysed, and the increase in treatment was used as the gold standard for active disease. Results: 93 patients (90.3% women, 69.9% Caucasian) were studied: mean age was 43.8 years, mean disease duration 10 years. There were 43 patients (46.2%) with a difference in SLEDAI-2000 score between the two raters and this difference was ⩾4 in 19 patients (20.4%). Agreement for each of the items in SLEDAI-2000 was between 81.7 and 100%. 35 patients (37.6%) had high activity on BILAG-2004 but a low SLEDAI-2000 score, of which 48.6% had treatment increased. There were only five patients (5.4%) with low activity on BILAG-2004 but a high SLEDAI-2000 score. Conclusions: SLEDAI-2000 is a reliable index to assess systemic lupus erythematosus disease activity but it is less able than the BILAG-2004 index to detect active disease requiring increased treatment.
Systemic Lupus International Collaborating Clinics (SLICC) comprises 27 centres from 11 countries. An inception cohort of 918 SLE patients has been assembled according to a standardized protocol between 2000 and 2006. Clinical features, classic coronary artery disease (CAD) risk factors, as well as other potential risk factors were collected. Of the 918 patients 89% were females, and of multi racial origin. Less than half the patients were living in a permanent relationship, 58% had post secondary education and 51% were employed. Eight percent had family history of SLE. At enrolment, with at mean age of diagnosis of 34.5 years, a significant number of patients already had CAD risk factors, such as hypertension (33%) and hypercholesterolemia (36%). Only 15% of the patients were postmenopausal, 16% were current smokers and 3.6% had diabetes at entry to the SLICC-RAS (Registry for Atherosclerosis). A number of patients in this multi-racial, multi-ethnic inception cohort of lupus patients have classic CAD risk factors within a mean of 5.4 months from diagnosis. This cohort will be increased to 1500 patients to be followed yearly for 10 years. This will provide a unique opportunity to evaluate risk factors for accelerated atherosclerosis in SLE.