Predicting risk for radiographic damage in rheumatoid arthritis:comparative analysis of the multi-biomarker disease activity score and conventional measures of disease activity in multiple studies

Pathophysiology and treatment of rheumatic disease

Rare Complications of Cervical Spine Surgery: Pseudomeningocoele.

STUDY DESIGN: This study was a retrospective, multicenter cohort study. OBJECTIVES: Rare complications of cervical spine surgery are inherently difficult to investigate. Pseudomeningocoele (PMC), an abnormal collection of cerebrospinal fluid that communicates with the subarachnoid space, is one such complication. In order to evaluate and better understand the incidence, presentation, treatment, and outcome of PMC following cervical spine surgery, we conducted a multicenter study to pool our collective experience. METHODS: This study was a retrospective, multicenter cohort study of patients who underwent cervical spine surgery at any level(s) from C2 to C7, inclusive; were over 18 years of age; and experienced a postoperative PMC. RESULTS: Thirteen patients (0.08%) developed a postoperative PMC, 6 (46.2%) of whom were female. They had an average age of 48.2 years and stayed in hospital a mean of 11.2 days. Three patients were current smokers, 3 previous smokers, 5 had never smoked, and 2 had unknown smoking status. The majority, 10 (76.9%), were associated with posterior surgery, whereas 3 (23.1%) occurred after an anterior procedure. Myelopathy was the most common indication for operations that were complicated by PMC (46%). Seven patients (53%) required a surgical procedure to address the PMC, whereas the remaining 6 were treated conservatively. All PMCs ultimately resolved or were successfully treated with no residual effects. CONCLUSIONS: PMC is a rare complication of cervical surgery with an incidence of less than 0.1%. They prolong hospital stay. PMCs occurred more frequently in association with posterior approaches. Approximately half of PMCs required surgery and all ultimately resolved without residual neurologic or other long-term effects

Validating coronal magnetic field reconstruction methods using solar wind simulations and synthetic imagery

We present an ongoing effort within the ESA Modeling and Data Analysis Working Group (MADAWG) to determine automatically the magnetic connectivity between the solar surface and any point in interplanetary space. The goal is to produce predictions of the paths and propagation delays of plasma and energetic particle propagation. This is a key point for the data exploitation of the Solar Orbiter and Solar Probe Plus missions, and for establishing connections between remote and in-situ data. The background coronal magnetic field is currently determined via existing surface magnetograms and PFSS extrapolations, but the interface is ready to include different combinations of coronal field reconstruction methods (NLFFF, Solar Models), wind models (WSA, MULTI-VP), heliospheric models (Parker spiral, ENLIL, EUHFORIA). Some model realisations are also based on advanced magnetograms based on data assimilation techniques (ADAPT) and the HELCATS catalogue of simulations. The results from the different models will be combined in order to better assess the modelling uncertainties. The wind models provide synthetic white-light and EUV images which are compared to coronographic imagery, and the heliospheric models provide estimations of synthetic in-situ data wich are compared to spacecraft data. A part of this is work (wind modelling) is supported by the FP7 project #606692 (HELCATS)

C5 Palsy After Cervical Spine Surgery: A Multicenter Retrospective Review of 59 Cases.

STUDY DESIGN: A multicenter, retrospective review of C5 palsy after cervical spine surgery. OBJECTIVE: Postoperative C5 palsy is a known complication of cervical decompressive spinal surgery. The goal of this study was to review the incidence, patient characteristics, and outcome of C5 palsy in patients undergoing cervical spine surgery. METHODS: We conducted a multicenter, retrospective review of 13 946 patients across 21 centers who received cervical spine surgery (levels C2 to C7) between January 1, 2005, and December 31, 2011, inclusive. P values were calculated using 2-sample t test for continuous variables and χ(2) tests or Fisher exact tests for categorical variables. RESULTS: Of the 13 946 cases reviewed, 59 patients experienced a postoperative C5 palsy. The incidence rate across the 21 sites ranged from 0% to 2.5%. At most recent follow-up, 32 patients reported complete resolution of symptoms (54.2%), 15 had symptoms resolve with residual effects (25.4%), 10 patients did not recover (17.0%), and 2 were lost to follow-up (3.4%). CONCLUSION: C5 palsy occurred in all surgical approaches and across a variety of diagnoses. The majority of patients had full recovery or recovery with residual effects. This study represents the largest series of North American patients reviewed to date

Physiologically-based pharmacokinetic and toxicokinetic models for estimating human exposure to five toxic elements through oral ingestion

Biological monitoring and physiologically-based pharmacokinetic (PBPK) modelling are useful complementary tools in quantifying human exposure to elements in the environment. In this work, we used PBPK models to determine the optimal time for collecting biological samples in a longitudinal study to determine if participants who consumed allotment produce had been exposed to arsenic, cadmium, chromium, nickel or lead. There are a number of PBPK models for these elements published in the literature, which vary in size, complexity and application, given the differences in physiochemical properties of the elements, organs involved in metabolism and exposure pathways affected. We selected PBPK models from the literature to simulate the oral ingestion pathway from consumption of allotment produce. Some models required modification by reducing or removing selected compartments whilst still maintaining their original predictability. The performance of the modified models was evaluated by comparing the predicted urinary and blood elemental levels with experimental data and other model simulations published in the literature. Overall, the model predictions were consistent with literature data (r > 0.7, p < 0.05), and were influential in predicting when samples should be collected. Our results demonstrate the use of mathematical modelling in informing and optimising the design of longitudinal studies

The multi-biomarker disease activity score tracks response to rituximab treatment in rheumatoid arthritis patients: a post hoc analysis of three cohort studies

BACKGROUND: A multi-biomarker disease activity (MBDA) score has been validated as an objective measure of disease activity in rheumatoid arthritis (RA) and shown to track response to treatment with several disease-modifying anti-rheumatic drugs (DMARDs). The objective of this study was to evaluate the ability of the MBDA score to track response to treatment with rituximab. METHODS: Data were used from 57 RA patients from three cohorts treated with rituximab 1000 mg and methylprednisolone 100 mg at days 1 and 15. The MBDA score was assessed in serum samples obtained at baseline and 6 months. Spearman's rank correlation coefficients were calculated for baseline values, 6-month values, and change from baseline to 6 months (∆), between MBDA score and the following measures: disease activity score assessing 28 joints (DAS28) using erythrocyte sedimentation rate (ESR) or high-sensitivity C-reactive protein (hsCRP), ESR, (hs)CRP, swollen and tender joint counts assessing 28 joints (SJC28, TJC28), patient visual analogue scale for general health (VAS-GH), health assessment questionnaire (HAQ), and radiographic progression over 12 months using Sharp/van der Heijde score (SHS), as well as six bone turnover markers. Additionally, multivariable linear regression analyses were performed using these measures as dependent variable and the MBDA score as independent variable, with adjustment for relevant confounders. The association between ∆MBDA score and European League Against Rheumatism (EULAR) response at 6 months was assessed with adjustment for relevant confounders. RESULTS: At baseline, the median MBDA score and DAS28-ESR were 54.0 (IQR 44.3-70.0) and 6.3 (IQR 5.4-7.1), respectively. MBDA scores correlated significantly with DAS28-ESR, DAS28-hsCRP, ESR and (hs)CRP at baseline and 6 months. ∆MBDA score correlated significantly with changes in these measures. ∆MBDA score was associated with EULAR good or moderate response (adjusted OR = 0.89, 95% CI = 0.81-0.98, p = 0.02). Neither baseline MBDA score nor ΔMBDA score correlated statistically significantly with ∆SHS (n = 11) or change in bone turnover markers (n = 23), although ∆SHS ≥ 5 was observed in 5 (56%) of nine patients with high MBDA scores. CONCLUSIONS: We have shown, for the first time, that the MBDA score tracked disease activity in RA patients treated with rituximab and that change in MBDA score reflected the degree of treatment response

Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups

Background: Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without previous cardiovascular disease (primary prevention). Methods: In CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 4401 participants with type 2 diabetes mellitus and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care. Results: Primary prevention participants (n=2181, 49.6%) were younger (61 versus 65 years), were more often female (37% versus 31%), and had shorter duration of diabetes mellitus (15 years versus 16 years) compared with secondary prevention participants (n=2220, 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78 [95% CI, 0.61-1.00]), nonfatal myocardial infarction (HR, 0.81 [95% CI, 0.59-1.10]), and nonfatal stroke (HR, 0.80 [95% CI, 0.56-1.15]). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction &gt;0.5 for each outcome). Conclusions: Canagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, including in participants who did not have previous cardiovascular disease