An updated matrix to predict rapid radiographic progression of early rheumatoid arthritis patients: pooled analyses from several databases

Rheumatology ◽  
2019 ◽  
Vol 59 (8) ◽  
pp. 1842-1852 ◽  
Author(s):  
Antoine Vanier ◽  
Josef S Smolen ◽  
Cornelia F Allaart ◽  
Ronald Van Vollenhoven ◽  
Patrick Verschueren ◽  
...  

Abstract Objective In early RA, some patients exhibit rapid radiographic progression (RRP) after one year, associated with poor functional prognosis. Matrices predicting this risk have been proposed, lacking precision or inadequately calibrated. We developed a matrix to predict RRP with high precision and adequate calibration. Methods Post-hoc analysis by pooling individual data from cohorts (ESPOIR and Leuven cohorts) and clinical trials (ASPIRE, BeSt and SWEFOT trials). Adult DMARD-naïve patients with active early RA for which the first therapeutic strategy after inclusion was to prescribe methotrexate or leflunomide were included. A logistic regression model to predict RRP was built. The best model was selected by 10-fold stratified cross-validation by maximizing the Area Under the Curve. Calibration and discriminatory power of the model were checked. The probabilities of RRP for each combination of levels of baseline characteristics were estimated. Results 1306 patients were pooled. 20.6% exhibited RRP. Four predictors were retained: rheumatoid factor positivity, presence of at least one RA erosion on X-rays, CRP > 30mg/l, number of swollen joints. The matrix estimates RRP probability for 36 combinations of level of baseline characteristics with a greatly enhanced precision compared with previously published matrices (95% CI: from ± 0.02 minimum to ± 0.08 maximum) and model calibration is excellent (P = 0.79). Conclusion A matrix proposing RRP probability with high precision and excellent calibration in early RA was built. Although the matrix has moderate sensitivity and specificity, it is easily usable and may help physicians and patients to make treatment decisions in daily clinical practice.

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 112.1-112
Author(s):  
L. Brandt ◽  
H. Schulze-Koops ◽  
T. Hügle ◽  
M. J. Nissen ◽  
H. Paul ◽  
...  

Background:The therapeutic aim for rheumatoid arthritis (RA) is to control disease activity and prevent radiographic progression. Various clinical scores are utilized to describe disease activity in RA patients. The DAS28 score can define states of low disease activity (LDA) and remission. Despite achieving LDA or remission, radiographic progression may nevertheless occur. However, the rates and frequency of this occurrence have not been analyzed in detail.Objectives:To describe the frequency and rate of radiographic progression in patients with persistent LDA or remission.Methods:Analysis of RA patients from the SCQM cohort. Persistent LDA or remission were defined as DAS 28 ≤3.2 or <2.6 respectively, at two subsequent follow up time points in the database. We included patients with at least two sets of radiographs within these intervals of LDA and/or remission. Radiographic progression was measured with the Ratingen-score (range 0-190), which describes joint erosions numerically. Repair was defined as an improvement in the Ratingen score >5 points/year and progression as >2 or >5 points change in the Ratingen score within one year.Results:Among 10’141 RA patients, 4’342 episodes of remission occurred in 3’927 patients with 1’776 sets of X rays available within these episodes. Similarly, 8’136 episodes of LDA in 6’765 patients and 2’358 sets of X rays were present within these intervals. For patients in LDA or remission, rates of repair were 5.5% and 4.8%, respectively, while for radiographic progression >5 points in the Ratingen score/year were 10.3% in both groups and for >2 points change of Ratingen score/year were 27.7 and 25.4%, respectively).No differences for demographic factors or measures of disease activity, rheumatoid factor or ACPA were found comparing patients with radiographic progression or non-progression despite LDA or remission at the beginning of the episode of LDA and/or remission.Interestingly, 42.9% of patients in LDA with progression of >5 points in the Ratingen score/year were current smokers vs 29.4% among the non-progressors (X2 = 6.55, p = 0.01). This significant difference vanished when the cut-off for radiographic progression was set at >2 points yearly change in Ratingen score or in patients in remission.Conclusion:Radiographic progression despite LDA or remission are more frequent than expected. No differences in radiographic progression were found comparing LDA and remission suggesting that the goal of LDA is appropriate. Smoking seems to be an independent risk factor for radiographic progression despite LDA. Why the effect of smoking could was not demonstrated in patients in remission, remains unclear.Disclosure of Interests:Lena Brandt: None declared, Hendrik Schulze-Koops: None declared, Thomas Hügle Consultant of: GSK, Abbvie, Pfizer, Jansen, Novartis, Eli Lilly., Michael J. Nissen Consultant of: Abbvie, Celgene, Eli-Lilly, Janssen, Novartis and Pfizer, Hasler paul Consultant of: Abbvie, Lilly, Rudiger Muller Consultant of: AbbVie, Novartis, Grant/research support from: Gebro


2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Peter M. ten Klooster ◽  
Letty G. A. Versteeg ◽  
Martijn A. H. Oude Voshaar ◽  
Inmaculada de la Torre ◽  
Francesco De Leonardis ◽  
...  

Abstract Background The aim of this retrospective study was to examine the longitudinal association between disease activity and radiographic damage in a cohort of patients with early RA (symptom onset < 1 year) treated according to treat-to-target (T2T) therapy. Methods Baseline to 3-year follow-up data were used from patients included in the DREAM remission induction cohort. Patients received protocolized T2T treatment, aimed at 28-joint disease activity score-erythrocyte sedimentation rate (DAS28-ESR) remission. Disease activity (DAS28-ESR and C-reactive protein, CRP) were assessed at least every 3 months; X-rays of the hand and feet at inclusion, 6 months, and 1, 2, and 3 years were scored using modified Sharp/van der Heijde scoring (SHS). Between and within-person associations between time-integrated disease activity and radiographic progression over time were examined. Results A subset of 229 out of 534 included patients were available for analysis. At the between-patient level, time-integrated DAS28-ESR scores were not significantly correlated with progression at the 6 month and 2-year follow-up and only weakly at the 1-year (Pearson’s correlation coefficient r = 0.17, P < 0.05) and 3-year follow-up (r = 0.21, P < 0.05). Individual slopes of the relationship between DAS28-ESR and progression scores in each time interval were significantly correlated over time and the slope of the first 6 months was moderately associated with this slope at later time points (r between 0.39 and 0.59; P values < 0.001). Between 15.9 to 22.7% and 16.7 to 38.5% of patients with low and moderate time-integrated disease activity, respectively, experienced relevant (ΔSHS ≥ 3) radiographic progression at the different time intervals. Analyses using CRP showed similar results. Conclusions In early RA patients treated according to T2T, radiographic progression appears to be an individually determined disease process, driven by factors other than consistent high disease activity. For individual patients, the intra-patient relation between disease activity and cumulative radiographic damage during the first 6 months is a good indicator for this relation in later years. Trial registration Netherlands Trial Register NTR578, 12 January 2006.


Author(s):  
Richard B. Mott ◽  
John J. Friel ◽  
Charles G. Waldman

X-rays are emitted from a relatively large volume in bulk samples, limiting the smallest features which are visible in X-ray maps. Beam spreading also hampers attempts to make geometric measurements of features based on their boundaries in X-ray maps. This has prompted recent interest in using low voltages, and consequently mapping L or M lines, in order to minimize the blurring of the maps.An alternative strategy draws on the extensive work in image restoration (deblurring) developed in space science and astronomy since the 1960s. A recent example is the restoration of images from the Hubble Space Telescope prior to its new optics. Extensive literature exists on the theory of image restoration. The simplest case and its correspondence with X-ray mapping parameters is shown in Figures 1 and 2.Using pixels much smaller than the X-ray volume, a small object of differing composition from the matrix generates a broad, low response. This shape corresponds to the point spread function (PSF). The observed X-ray map can be modeled as an “ideal” map, with an X-ray volume of zero, convolved with the PSF. Figure 2a shows the 1-dimensional case of a line profile across a thin layer. Figure 2b shows an idealized noise-free profile which is then convolved with the PSF to give the blurred profile of Figure 2c.


2020 ◽  
pp. 32-33
Author(s):  
Nikolay I. Antonov ◽  

Pelvic injuries account for 16 to 25% of all skeletal trauma in small pets. Small dogs as companion dogs are now widespread. Unusual exterior and behavioral features have made them popular and at the same time vulnerable in the modern urban environment. The author defined the nature of injuries and adapted technique of transosseous osteosynthesis for the treatment of toy-breed dogs with pelvic trauma. The study of the X-rays in 226 dogs with pelvic injuries demonstrated that toy-breed dogs accounted for 16% of the total. Multiple pelvic trauma was revealed in 95% of them. Surgical treatment was performed in 24 dogs, conservative one - in 13, that amounted to 65% and 35%, respectively. Surgical treatment consisted in open juxtaposing of fragments and focal transosseous and/or internal osteosynthesis with subsequent external fixation using devices of various designs. The external structures were of three types: half-ring support or U-shaped staple, pair of parallel curved plates connected by two threaded rods with each other, and pair of curved plates located bilaterally on both sides of the pelvis and connected by two threaded rods with the help of threaded ends. The terms of fixation for pelvic injuries in toy-breed dogs at the age under one year were 42 days on the average, and in the dogs at the age above one year - 60 days. Surgical treatment in toy-breed dogs with pelvic injuries was performed more often in comparison with conservative one. Pelvic trauma was accompanied by pronounced pain shock. The osteosynthesis techniques used in toy-breed dogs are little traumatic and not limiting functions thereby contributing to recovery of all the structures of pelvis and pelvic limbs.


Author(s):  
Stefan Kabisch ◽  
Caroline Honsek ◽  
Margrit Kemper ◽  
Christiana Gerbracht ◽  
Ayman M. Arafat ◽  
...  

Abstract Aims As the first long-term RCT on insoluble cereal fibre, the optimal fibre trial demonstrated glycometabolic benefits, confirming cohort studies. The combined study intervention of lifestyle recommendations and supplementation with insoluble oat hulls fibre allows to clarify, which amount of fibre is required for a beneficial effect. Methods One hundred and eighty participants with impaired glucose tolerance underwent the one-year PREDIAS lifestyle programme and received a blinded, randomized fibre or placebo supplement for two years. We conducted a regression analyses and cut-off-based tertile comparisons in subjects with full data on dietary compliance (food records and accounted supplement; n = 120) after one year, investigating effects on fasting blood parameters, oral glucose tolerance test and anthropometry. Results We found a nonlinear inverse relation between fibre intake and change in postprandial 2-h glucose levels, showing a metabolic benefit beyond 14 g and a plateau beyond 25 g of total insoluble fibre per day. 2-h glucose levels improved significantly stronger in both upper tertiles (−0.9 [−1.6;−0.2] mmol/l, p = 0.047, and −0.6 [−1.6;0.3] mmol/l, p = 0.010) compared to the lowest tertile (0.1 [−1.2;1.1] mmol/l), also when adjusted for changes in bodyweight. Subjects with the highest fibre intake showed superior effects on fasting and postprandial insulin resistance, hepatic insulin clearance, leucocyte count and fatty liver index. Conclusions Extending the knowledge on the benefits of insoluble oat hulls fibre, our post hoc analysis demonstrates a dose effect for glycaemia and associated metabolic markers. Further research is needed in order to replicate our findings in larger trials.


2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Paul Emery ◽  
Patrick Durez ◽  
Axel J. Hueber ◽  
Inmaculada de la Torre ◽  
Esbjörn Larsson ◽  
...  

AbstractBaricitinib is an oral selective inhibitor of Janus kinase (JAK)1 and JAK2 that has proved effective and well tolerated in the treatment of rheumatoid arthritis (RA) in an extensive programme of clinical studies of patients with moderate-to-severe disease. In a phase 2b dose-ranging study of baricitinib in combination with traditional disease-modifying antirheumatic drugs (DMARDs) in RA patients, magnetic resonance imaging showed that baricitinib 2 mg or 4 mg once daily provided dose-dependent suppression of synovitis, osteitis, erosion and cartilage loss at weeks 12 and 24 versus placebo. These findings correlated with clinical outcomes and were confirmed in three phase 3 studies (RA-BEGIN, RA-BEAM and RA-BUILD) using X-rays to assess structural joint damage. In patients naïve to DMARDs (RA-BEGIN study), baricitinib 4 mg once daily as monotherapy or combined with methotrexate produced smaller mean changes in structural joint damage than methotrexate monotherapy at week 24. Differences versus methotrexate were statistically significant for combined therapy. In patients responding inadequately to methotrexate (RA-BEAM study), baricitinib 4 mg plus background methotrexate significantly inhibited structural joint damage at week 24 versus placebo, and the results were comparable to those observed with adalimumab plus background methotrexate. In patients responding inadequately to conventional synthetic DMARDs (csDMARDs; RA-BUILD study), baricitinib 4 mg again significantly inhibited radiographic progression compared with placebo at week 24. Benefits were also observed with baricitinib 2 mg once daily, but the effects of baricitinib 4 mg were more robust. The positive effects of baricitinib 4 mg on radiographic progression continued over 1 and 2 years in the long-term extension study RA-BEYOND, with similar effects to adalimumab and significantly greater effects than placebo. Findings from the phase 3 studies of patients with RA were supported by preclinical studies, which showed that baricitinib has an osteoprotective effect, increasing mineralisation in bone-forming cells. In conclusion, baricitinib 4 mg once daily inhibits radiographic joint damage progression in patients with moderate-to-severe RA who are naïve to DMARDs or respond inadequately to csDMARDs, including methotrexate, and the beneficial effects are similar to those observed with adalimumab.


1997 ◽  
Vol 15 (1) ◽  
pp. 133-138 ◽  
Author(s):  
A.M. Buyko ◽  
O.M. Burenkov ◽  
V.K. Chernyshev ◽  
S.F. Garanin ◽  
S.D. Kuznetsov ◽  
...  

Powerful pulse installations are usually used to produce large yields of X-ray radiation. With an increase of the stored energy up to 100 MJ, the costof a single experiment on these installations becomes comparable to the cost of a shot with explosive magnetic generators (EMG), according to expert estimates. The physical scheme of a device with a changeable mass liner forlarge soft X-ray (in the range of 0.3 to 0.5 keV) yields eneration is investigated. The scheme investigated is substantially free from difficulties connected with high precision liners and fast switches for current pulse sharpening.


2003 ◽  
pp. 1-6 ◽  
Author(s):  
M Wasniewska ◽  
F De Luca ◽  
A Cassio ◽  
N Oggiaro ◽  
P Gianino ◽  
...  

OBJECTIVE: To evaluate in a cohort of infants with congenital hypothyroidism (CH): (a) the frequency of bone maturation (BM) retardation at birth and (b) whether BM delay at birth may be considered as a tool to make a prognosis of psychomotor status at the age of 1 Year, irrespective of other variables related to treatment. DESIGN: BM at birth, CH severity and developmental quotient (DQ) at the age of 1 Year were retrospectively evaluated in 192 CH infants selected by the following inclusion criteria: (a) gestation age ranging between 38 and 42 weeks; (b) onset of therapy within the first Month of life; (c) initial thyroxine (l-T(4)) dosage ranging from 10 to 12 microg/kg/day; (d) normalization of serum thyrotropin (TSH) levels before the age of 3 Months; (e) Monthly adjustments of l-T(4) dose during the first Year of life with serum TSH levels ranging from 0.5 to 4 mIU/l; (f) no major diseases and/or physical handicaps associated with CH; (g) availability of both thyroid scanning and knee X-rays at the time of treatment initiation; (h) availability of DQ assessment at an average age of 12 Months. METHODS: BM was considered normal if the distal femur bony nucleus diameter exceeded 3 mm (group A) or retarded if either this nucleus was absent (subgroup B1) or its diameter was <3 mm (subgroup B2). DQ was evaluated with the Brunet-Lezine test. RESULTS: In 44.3% of cases BM was either delayed (23.5%) or severely delayed (20.8%). The risk of BM retardation was higher in the patients with athyreosis than in the remaining patients (41/57 vs 44/135, chi(2)=25.13, P<0.005). BM-retarded infants showed a more severe biochemical picture of CH at birth and a lower DQ at the age of one Year compared with the group A patients. If compared with infants of subgroup B2 those of subgroup B1 exhibited significantly lower T(4) levels at birth and a more frequent association with athyreosis (70.0 vs 30.0%; chi(2)=7.49, P<0.01), whereas DQ was superimposable in both subgroups. CONCLUSIONS: (a) BM at birth is delayed in almost half of CH patients and (b) CH severity per se can affect DQ at the age of 1 Year irrespective of other variables related to therapy.


2018 ◽  
pp. 83-87
Author(s):  
Marianna Takács ◽  
János Oláh

An apiary trial was conducted in 2016 August to October in Szabolcs-Szatmár-Bereg County, Nyírmada to evaluate the influence of queen’s age on the Varroa destructor-burden in the treatment colonies. Sixty colonies of bees belonging to the subspecies Apis mellifera carnica pannonica in Hunor loading hives (with 10 frames in the brood chamber/deep super) were used. The colonies were treated with amitraz and the organophosphate pesticide coumaphos active ingredients. The amitraz treatment includes 6 weeks. The coumaphos treatment with Destructor 3.2% can be used for both diagnosis and treatment of Varroasis. For diagnosis, one treatment is sufficient. For control, two treatments at an interval of seven days are required. The colonies were grouped by the age of the queen: 20 colonies with one-year-old, 20 colonies with two-year-old and 20 colonies with three-year-old queen. The mite mortality of different groups was compared. The number of fallen mites was counted at the white bottom boards. The examination of spring growth of honey bee colonies has become necessary due to the judgement of efficiency of closing treatment. The data was recorded seven times between 16th March 2017 and 19th May 2017. Data on fallen mites were subjected to one-way analysis of variance (ANOVA) and Post-Hoc Tukey-test. Statistical analysis was performed using the software of IBM SPSS (version 21.). During the first two weeks after treatments, the number of fallen mites was significantly higher in the older queen’s colonies (Year 2014). The total mite mortality after amitraz treatment in the younger queen’s colonies was lower (P<0.05) compared to the three-year-old queen’s colonies. According to Takács and Oláh (2016) although the mitemortality tendency, after the coumaphos (closing) treatment in colonies which have Year 2014 queen showed the highest rate, considering the mite-burden the colonies belongs to the average infected category. The colonial maintenance ability of three-year-old queen cannot be judged based on the influencing effect on the mite-burden. The importance of the replacement of the queen was judged by the combined effect of several factors. During the spring-growth study (16th March–19th May) was experienced in the three-year-old queen’s colonies the number of brood frames significantly lower compared to the one- and two-year-old queen’s colonies. In the study of 17th April and 19th May each of the three queen-year-groups were varied. Therefore in the beekeeping season at different times were determined the colonial maintenance ability of queens by more factors: efficiency of closing treatment in early spring, the spring-growth of bee colonies, the time of population shift (in current study, this time was identical in each queen-year), honey production (from black locust).


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