Rheumatoid arthritis - clinical aspects: 134. Predictors of Joint Damage in South Africans with Rheumatoid Arthritis

Background: Rheumatoid arthritis (RA) causes progressive joint damage and functional disability. Studies on factors affecting joint damage as clinical outcome are lacking in Africa. The aim of the present study was to identify predictors of joint damage in adult South Africans with established RA. Methods: A cross-sectional study of 100 black patients with RA of >5 years were assessed for joint damage using a validated clinical method, the RA articular damage (RAAD) score. Potential predictors of joint damage that were documented included socio-demographics, smoking, body mass index (BMI), disease duration, delay in disease modifying antirheumatic drug (DMARD) initiation, global disease activity as measured by the disease activity score (DAS28), erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and autoantibody status. The predictive value of variables was assessed by univariate and stepwise multivariate regression analyses. A p value <0.05 was considered significant. Results: The mean (SD) age was 56 (9.8) years, disease duration 17.5 (8.5) years, educational level 7.5 (3.5) years and DMARD lag was 9 (8.8) years. Female to male ratio was 10:1. The mean (SD) DAS28 was 4.9 (1.5) and total RAAD score was 28.3 (12.8). The mean (SD) BMI was 27.2 kg/m2 (6.2) and 93% of patients were rheumatoid factor (RF) positive. More than 90% of patients received between 2 to 3 DMARDs. Significant univariate predictors of a poor RAAD score were increasing age (p = 0.001), lower education level (p = 0.019), longer disease duration (p < 0.001), longer DMARD lag (p = 0.014), lower BMI (p = 0.025), high RF titre (p < 0.001) and high ESR (p = 0.008). The multivariate regression analysis showed that the only independent significant predictors of a higher mean RAAD score were older age at disease onset (p = 0.04), disease duration (p < 0.001) and RF titre (p < 0.001). There was also a negative association between BMI and the mean total RAAD score (p = 0.049). Conclusions: Patients with longstanding established RA have more severe irreversible joint damage as measured by the clinical RAAD score, contrary to other studies in Africa. This is largely reflected by a delay in the initiation of early effective treatment. Independent of disease duration, older age at disease onset and a higher RF titre are strongly associated with more joint damage. The inverse association between BMI and articular damage in RA has been observed in several studies using radiographic damage scores. The mechanisms underlying this paradoxical association are still widely unknown but adipokines have recently been suggested to play a role. Disclosure statement: C.I. has received a research grant from the Connective Tissue Diseases Research Fund, University of the Witwatersrand. All other authors have declared no conflicts of interes

Rheumatoid arthritis - treatment: 180. Utility of Body Weight Classified Low-Dose Leflunomide in Japanese Rheumatoid Arthritis

Background: In Japan, more than 20 rheumatoid arthritis (RA) patients died of interstitial pneumonia (IP) caused by leflunomide (LEF) were reported, but many of them were considered as the victims of opportunistic infection currently. In this paper, efficacy and safety of low-dose LEF classified by body weight (BW) were studied. Methods: Fifty-nine RA patients were started to administrate LEF from July 2007 to July 2009. Among them, 25 patients were excluded because of the combination with tacrolimus, and medication modification within 3 months before LEF. Remaining 34 RA patients administered 20 to 50 mg/week of LEF were followed up for 1 year and enrolled in this study. Dose of LEF was classified by BW (50 mg/week for over 50 kg, 40 mg/week for 40 to 50 kg and 20 to 30 mg/week for under 40 kg). The average age and RA duration of enrolled patients were 55.5 years old and 10.2 years. Prednisolone (PSL), methotrexate (MTX) and etanercept were used in 23, 28 and 2 patients, respectively. In case of insufficient response or adverse effect, dosage change or discontinuance of LEF were considered. Failure was defined as dosages up of PSL and MTX, or dosages down or discontinuance of LEF. Last observation carried forward method was used for the evaluation of failed patients at 1 year. Results: At 1 year after LEF start, good/ moderate/ no response assessed by the European League Against Rheumatism (EULAR) response criteria using Disease Activity Score, including a 28-joint count (DAS28)-C reactive protein (CRP) were showed in 14/ 10/ 10 patients, respectively. The dosage changes of LEF at 1 year were dosage up: 10, same dosage: 5, dosage down: 8 and discontinuance: 11 patients. The survival rate of patients in this study was 23.5% (24 patients failed) but actual LEF continuous rate was 67.6% (11 patients discontinued) at 1 year. The major reason of failure was liver dysfunction, and pneumocystis pneumonia was occurred in 1 patient resulted in full recovery. One patient died of sepsis caused by decubitus ulcer infection. DAS28-CRP score was decreased from 3.9 to 2.7 significantly. Although CRP was decreased from 1.50 to 0.93 mg/dl, it wasn't significant. Matrix metalloproteinase (MMP)-3 was decreased from 220.0 to 174.2 ng/ml significantly. Glutamate pyruvate transaminase (GPT) was increased from 19 to 35 U/l and number of leukocyte was decreased from 7832 to 6271 significantly. DAS28-CRP, CRP, and MMP-3 were improved significantly with MTX, although they weren't without MTX. Increase of GPT and leukopenia were seen significantly with MTX, although they weren't without MTX. Conclusions: It was reported that the risks of IP caused by LEF in Japanese RA patients were past IP history, loading dose administration and low BW. Addition of low-dose LEF is a potent safe alternative for the patients showing unsatisfactory response to current medicines, but need to pay attention for liver function and infection caused by leukopenia, especially with MTX. Disclosure statement: The authors have declared no conflicts of interes

Direct Skeletal Fixation in bilateral above knee amputees following blast: 2 year follow up results from the initial cohort of UK service personnel.

AIMS The aim of the study is to evaluate the clinical outcome and complications from the initial cohort of blast injured bilateral lower limb, above knee amputees who underwent Direct Skeletal Fixation (DSF). PATIENTS AND METHODS We undertook a retrospective analysis of a prospective data base identifying patients who had undergone implantation with the Australian Osseointegration Group of Australia-Osseointegration Prosthetic Limb (OGAP-OPL) prosthesis, with minimum 24 months follow up. Patient demographics, injury profile, and polymicrobial colonisation status were recorded. Physical functional performance measures recorded were the 6 minute Walk Test (6-MWT) and patient reported outcome measures were the Short Form Health Survey-36 (SF-36). Post operatively, complications including infection, re-operation, and fracture were recorded. RESULTS 7 patients (14 femora) were identified (mean age 29.8yrs), all injured by dismounted blast. Mean follow up was 46 months. All were polytrauma patients and all had previous polymicrobial colonisation. Following surgery, all patients mobilised with significant improvement in 6-minute walk time, with a mean improvement of 154 m (248 m vs 402 m, p = 0.018). The physical component score for the SF-36 demonstrated a statistically significant improvement from 34.65 to 54.5 (p = 0.018) and the mental component score demonstrated a similar improvement (41.55-58.19 p = 0.018). At follow up, no patient required explantation of the implant. Each had been prescribed a minimum of 1 course of antibiotics with no evidence of deep infection. CONCLUSION DSF is an option for amputees who, due to the nature of their injuries, may not be able to tolerate traditional suspension socket prostheses and have exhausted all other treatment options. At a minimum of 2 year follow up, the absence of significant infective complications suggests DSF may be utilised in the blast injured despite chronic polymicrobial colonisation. Longer term surveillance of these patients is required to assess the long-term suitability of this technique in this cohort of patients

Pituitary dysfunction after blast traumatic brain injury

Objective: Pituitary dysfunction is a recognized consequence of traumatic brain injury (TBI) that causes cognitive, psychological, and metabolic impairment. Hormone replacement offers a therapeutic opportunity. Blast TBI (bTBI) from improvised explosive devices is commonly seen in soldiers returning from recent conflicts. We investigated: (1) the prevalence and consequences of pituitary dysfunction following moderate to severe bTBI and (2) whether it is associated with particular patterns of brain injury. Methods: Nineteen male soldiers with moderate to severe bTBI (median age = 28.3 years) and 39 male controls with moderate to severe nonblast TBI (nbTBI; median age = 32.3 years) underwent full dynamic endocrine assessment between 2 and 48 months after injury. In addition, soldiers had structural brain magnetic resonance imaging, including diffusion tensor imaging (DTI), and cognitive assessment. Results: Six of 19 (32.0%) soldiers with bTBI, but only 1 of 39 (2.6%) nbTBI controls, had anterior pituitary dysfunction (p = 0.004). Two soldiers had hyperprolactinemia, 2 had growth hormone (GH) deficiency, 1 had adrenocorticotropic hormone (ACTH) deficiency, and 1 had combined GH/ACTH/gonadotrophin deficiency. DTI measures of white matter structure showed greater traumatic axonal injury in the cerebellum and corpus callosum in those soldiers with pituitary dysfunction than in those without. Soldiers with pituitary dysfunction after bTBI also had a higher prevalence of skull/facial fractures and worse cognitive function. Four soldiers (21.1%) commenced hormone replacement(s) for hypopituitarism. Interpretation: We reveal a high prevalence of anterior pituitary dysfunction in soldiers suffering moderate to severe bTBI, which was more frequent than in a matched group of civilian moderate to severe nbTBI subjects. We recommend that all patients with moderate to severe bTBI should routinely have comprehensive assessment of endocrine function

The Stanford Hall consensus statement for post-COVID-19 rehabilitation

The highly infectious and pathogenic novel coronavirus (CoV), severe acute respiratory syndrome (SARS)-CoV-2, has emerged causing a global pandemic. Although COVID-19 predominantly affects the respiratory system, evidence indicates a multisystem disease which is frequently severe and often results in death. Long-term sequelae of COVID-19 are unknown, but evidence from previous CoV outbreaks demonstrates impaired pulmonary and physical function, reduced quality of life and emotional distress. Many COVID-19 survivors who require critical care may develop psychological, physical and cognitive impairments. There is a clear need for guidance on the rehabilitation of COVID-19 survivors. This consensus statement was developed by an expert panel in the fields of rehabilitation, sport and exercise medicine (SEM), rheumatology, psychiatry, general practice, psychology and specialist pain, working at the Defence Medical Rehabilitation Centre, Stanford Hall, UK. Seven teams appraised evidence for the following domains relating to COVID-19 rehabilitation requirements: pulmonary, cardiac, SEM, psychological, musculoskeletal, neurorehabilitation and general medical. A chair combined recommendations generated within teams. A writing committee prepared the consensus statement in accordance with the appraisal of guidelines research and evaluation criteria, grading all recommendations with levels of evidence. Authors scored their level of agreement with each recommendation on a scale of 0–10. Substantial agreement (range 7.5–10) was reached for 36 recommendations following a chaired agreement meeting that was attended by all authors. This consensus statement provides an overarching framework assimilating evidence and likely requirements of multidisciplinary rehabilitation post COVID-19 illness, for a target population of active individuals, including military personnel and athletes