Clinical outcomes in patients with systemic lupus erythematosus treated with belimumab in clinical practice settings: a retrospective analysis of results from the OBSErve study in Switzerland

AIMS OF THE STUDY To describe patterns of systemic lupus erythematosus (SLE) care and the clinical effectiveness of belimumab plus standard of care therapy in a real-world clinical setting in Switzerland. METHODS This multicentre, observational, retrospective cohort study included adults with SLE who initiated belimumab as part of their usual care at least six months before data analysis. The primary outcome was the overall clinical response, assessed by a physician on a Physician’s Global Assessment-like scale, to six months’ treatment with belimumab. Secondary outcomes included improvement in disease activity, SLE manifestations and changes in corticosteroid use. RESULTS 53 patients (81% female) from three hospitals were included. At index (belimumab initiation), 23 patients (43%) had mild, 23 (43%) had moderate, and 7 (13%) had severe SLE. Overall improvement in disease activity in patients receiving belimumab was: ≥80% in 6 patients (11%), ≥50% in 12 (23%), ≥20% in 31 (58%), <20% in 13 (25%), and no improvement in 9 (17%). Mean Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index score decreased from 8.0 at index to 3.6 at six months post index in the 27 patients assessed. In addition, a ≥50% improvement in arthritis, fatigue, rash, low complement (C3, C4 or total haemolytic complement activity), and anti-double-stranded deoxyribonucleic acid antibody levels was experienced six months post index by 10 (38%), 3 (16%), 6 (38%), 2 (12%) and 4 (16%) patients who presented the manifestations at index respectively. At index, 41 patients (77%) received oral corticosteroids at a mean dose of 11.6 mg/day, which decreased to 5.9 mg/day at six months post index. Of the 31 patients receiving a high dose of corticosteroids (≥7.5 mg/day) at index, 18 required <7.5 mg/day and a further two discontinued corticosteroids at six months post index. CONCLUSIONS This study provides real-world insight into belimumab use in clinical practice in Switzerland. In line with findings from other countries, Swiss patients with SLE who received belimumab demonstrated clinical and serological improvements in SLE and a reduction in corticosteroid use after six months of treatment

Prediction of in-hospital bleeding in acutely ill medical patients: External validation of the IMPROVE bleeding risk score.

INTRODUCTION Pharmacological thromboprophylaxis slightly increases bleeding risk. The only risk assessment model to predict bleeding in medical inpatients, the IMPROVE bleeding risk score, has never been validated using prospectively collected outcome data. METHODS We validated the IMPROVE bleeding risk score in a prospective multicenter cohort of medical inpatients. Primary outcome was in-hospital clinically relevant bleeding (CRB) within 14 days of admission, a secondary outcome was major bleeding (MB). We classified patients according to the score in high or low bleeding risk. We assessed the score's predictive performance by calculating subhazard ratios (sHRs) adjusted for thromboprophylaxis use, positive and negative predictive values (PPV, NPV), and the area under the receiver operating characteristic curves (AUC). RESULTS Of 1155 patients, 8 % were classified as high bleeding risk. CRB and MB within 14 days occurred in 0.94 % and 0.47 % of low-risk and in 5.6 % and 3.4 % of high-risk patients, respectively. Adjusted for thromboprophylaxis, classification in the high-risk group was associated with an increased risk of 14-day CRB (sHR 4.7, 95 % confidence interval [CI] 1.5-14.5) and MB (sHR 4.9, 95%CI 1.0-23.4). PPV was 5.6 % and 3.4 %, while NPV was 99.1 % and 99.5 % for CRB and MB, respectively. The AUC was 0.68 (95%CI 0.66-0.71) for CRB and 0.73 (95%CI 0.71-0.76) for MB. CONCLUSION The IMPROVE bleeding risk score showed moderate to good discriminatory power to predict bleeding in medical inpatients. The score may help identify patients at high risk of in-hospital bleeding, in whom careful assessment of the risk-benefit ratio of pharmacological thromboprophylaxis is warranted

Home-based virtual reality-augmented training improves lower limb muscle strength, balance, and functional mobility following chronic incomplete spinal cord injury

Key factors positively influencing rehabilitation and functional recovery after spinal cord injury (SCI) include training variety, intensive movement repetition, and motivating training tasks. Systems supporting these aspects may provide profound gains in rehabilitation, independent of the subject's treatment location. In the present study, we test the hypotheses that virtual reality (VR)-augmented training at home (i.e., unsupervised) is feasible with subjects with an incomplete SCI (iSCI) and that it improves motor functions such as lower limb muscle strength, balance, and functional mobility. In the study, 12 chronic iSCI subjects used a home-based, mobile version of a lower limb VR training system. The system included motivating training scenarios and combined action observation and execution. Virtual representations of the legs and feet were controlled via movement sensors. The subjects performed home-based training over 4 weeks, with 16-20 sessions of 30-45 min each. The outcome measures assessed were the Lower Extremity Motor Score (LEMS), Berg Balance Scale (BBS), Timed Up and Go (TUG), Spinal Cord Independence Measure mobility, Walking Index for Spinal Cord Injury II, and 10 m and 6 min walking tests. Two pre-treatment assessment time points were chosen for outcome stability: 4 weeks before treatment and immediately before treatment. At post-assessment (i.e., immediately after treatment), high motivation and positive changes were reported by the subjects (adapted Patients' Global Impression of Change). Significant improvements were shown in lower limb muscle strength (LEMS, P = 0.008), balance (BBS, P = 0.008), and functional mobility (TUG, P = 0.007). At follow-up assessment (i.e., 2-3 months after treatment), functional mobility (TUG) remained significantly improved (P = 0.005) in contrast to the other outcome measures. In summary, unsupervised exercises at home with the VR training system led to beneficial functional training effects in subjects with chronic iSCI, suggesting that it may be useful as a neurorehabilitation tool. Trial registration: Canton of Zurich ethics committee (EK-24/2009, PB_2016-00545), ClinicalTrials.gov: NCT02149186. Registered 24 April 2014

Influence of bisphosphonate therapy on bone geometry, volumetric bone density and bone strength of femoral shaft in postmenopausal women with rheumatoid arthritis.

BACKGROUND There is evidence that postmenopausal women with rheumatoid arthritis (RA) on glucocorticoid (GC) therapy and bisphosphonate (BP) have an increased risk for atypical subtrochanteric and atypical diaphyseal femoral fracture (AFF). The underlying mechanism has not been elucidated so far. Using peripheral quantitative computed tomography (pQCT), the aim of the present study was to compare bone geometry, volumetric bone mineral density (vBMD) and bone strength of femoral shaft in BP-treated and BP-naïve postmenopausal women with RA. METHODS Prospective cross-sectional pQCT scans were taken at 33 % of total femur of BP-treated and BP-naïve RA patients. Bone parameters of the two groups were compared and correlated to disease characteristics and muscle cross-sectional area (CSA). RESULTS A total of 60 consecutive postmenopausal RA patients, 20 with BP therapy and 40 BP-naïve, were included in the study. The median age of the subjects was 63.5 years (range 48-85 years), and median disease duration (RA) was 12.0 years (range 2-47 years). Height and weight of the patients of the two groups were comparable. Women in the BP group were on average 4.3 years older (p = 0.044), and duration since menopause was on average 5.76 years longer (p = 0.045). In the BP group, there was a 13.31 % reduced muscle cross-sectional area around the proximal thigh (p = 0.013); cortical CSA was smaller by 5.3 % (p = 0.043); however, total and medullary CSA, as well as cortical vBMD and the polar bone stress-strain index of the femoral shaft were similar in the two groups. In regression analysis, age, time since menopause and muscular CSA were significant factors determining cortical CSA, cortical thickness and femoral index (p < 0.05). Regression model showed no significant effect of BP therapy on bone geometry and density of the femoral diaphysis at 33 %. CONCLUSION Differences in cortical CSA between BP-treated and BP-naïve postmenopausal RA patients were found to be associated only with differences in age, time since menopause and muscle cross-sectional area around the proximal thigh. In interpreting our results, it should be kept in mind that BP was given only to patients with increased fracture risk. This fact might have a confounding effect on our findings of differences between the two groups

Prediction of very early major bleeding risk in acute pulmonary embolism: an independent external validation of the PE-SARD Bleeding Score.

BACKGROUND The PE-SARD Bleeding Score was derived to predict very early major bleeding (MB) in patients with acute pulmonary embolism (PE). Before adoption into practice the score requires external validation in different populations. OBJECTIVE We independently validated the PE-SARD in a prospective multicenter Swiss cohort of 687 patients aged ≥65 years with acute PE. METHODS The PE-SARD uses 3 variables (syncope, anemia, renal dysfunction) to classify patients into 3 categories of increasing bleeding risk. The outcomes were very early MB at 7 days (primary) and MB at later time points (secondary). We calculated the PE-SARD for each patient and the proportion of patients classified as low, intermediate, and high risk. To assess discrimination and calibration, we calculated the area under the receiver operating characteristic (ROC) curve and the Hosmer-Lemeshow goodness-of-fit test, respectively. RESULTS The prevalence of MB was 2.0% (14/687) at 7 days and 14.0% (96/687) after a median follow-up of 30 months. The PE-SARD classified 40.2%, 42.2%, and 17.6% of patients as low, intermediate, and high risk for MB, respectively. The frequency of observed very early MB at 7 days was 1.8% in low-, 2.1% in intermediate-, and 2.5% in high-risk patients. The area under the ROC curve was 0.52 (95%CI 0.48-0.56) at 7 days and increased to 0.60 (95%CI 0.56-0.64) at the end of follow-up. Score calibration was adequate (P>0.05) over the entire follow-up. CONCLUSION In our independent validation, the PE-SARD did not accurately predict very early MB and may not be transportable to older patients with PE

"On-site" prevention and education to improve cardiac pre-competition screening in competitive amateur athletes

STUDY/PRINCIPLES: To assess the effects of an "on-site" prevention and education programme to improve the cardiac screening in competitive amateur athletes. METHODS: We integrated an "on-site prevention and education programme" at the 2012 edition of the Swiss Alpine Marathon in Davos, Switzerland. After a specific lecture, the athletes could visit a "Sports-Cardiology-Section" at the official "medical-park". On an anonymised questionnaire, they could state their intention for a screening programme in general and after our "on-site" intervention. RESULTS: Among the 150 athletes who attended the medical day (3.3% of 4,500 finishers) the response rate was 82%. While 39 (31.7%) athletes were aware of "exercise related SCD", more than twice as many (64.2%) were not. 72.4% of the participants (n = 89) reported that they never had taken part in cardiac screening examinations. 70.7% (n = 87) runners were convinced that they would benefit from such a screening. 65.9% (n = 81) of the runners stated that our "on-site" prevention concept influenced their decision to consider a cardiac screening in the future. CONCLUSION: An "on-site prevention and education" concept for the prevention of SCD in competitive amateur athletes is feasible and successfully increased the athletes' awareness of the issue. The vast majority of athletes felt to have benefited from such a programme. The current study confirms that there is an alarming lack of preventive measures in the very large group of ambitious, competitive, amateur athletes that are frequently underprepared for challenging sports events