Long-term treatment with glucocorticoids (GCs) plays an important role in the management of arthritis patients, although the efficacy/safety balance is unfavorable. Alternatives with less (severe) ...adverse effects but with good efficacy are needed. Selective GC receptor modulators (SGRMs) are designed to engage the GC receptor with dissociative characteristics: transactivation of genes, which is mainly responsible for unwanted effects, is less strong while trans-repression of genes, reducing inflammation, is maintained. It is expected that SGRMs thus have a better efficacy/safety balance than GCs. A systematic review providing an overview of the evidence in arthritis is lacking.
To systematically review the current literature on efficacy and safety of oral SGRMs in comparison to GCs in arthritis.
A search was performed in Medline, Embase and the Cochrane Library, from inception dates of databases until May 2017. Experimental studies involving animal arthritis models or human material of arthritis patients, as well as clinical studies in arthritis patients were included, provided they reported original data. All types of arthritis were included. Data was extracted on the SGRM studied and on the GC used as reference standard; the design or setting of the study was extracted as well as the efficacy and safety results.
A total of 207 articles was retrieved of which 17 articles were eligible for our analysis. Two studies concerned randomized controlled trials (RCT), five studies were pre-clinical studies using human material, and 10 studies involved pre-clinical animal models (acute and/or chronic arthritis induced in mice or rats). PF-04171327, the only compound investigated in a clinical trial setting, had a better efficacy/safety balance compared to GCs: better clinical anti-inflammatory efficacy and similar safety.
Studies assessing both efficacy and safety of SGRMs are scarce. There is limited evidence for dissociation of anti-inflammatory and metabolic effects of the SGRMs studied. Development of many SGRMs is haltered in a preclinical phase. One SGRM showed a better clinical efficacy/safety balance.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In the second Computer-Assisted Management in Early Rheumatoid Arthritis trial, patients had started with methotrexate and 10 mg prednisone (MTX+pred) or placebo (MTX+plac). After the trial, ...prednisone was tapered and stopped, if possible. The objective was to compare, during the post-trial follow-up between the two former strategy groups, initiation of the first biological disease-modifying antirheumatic drug (bDMARD), radiographic outcome and onset of glucocorticoid (GC)-related comorbidities.
Data on prednisone and bDMARD use and onset of GC-related comorbidities were collected retrospectively. Sharp/van der Heijde scoring was performed. Data were analysed using Fisher's exact and Mann-Whitney U tests.
Of 218 patients post-trial follow-up data were available. The maximum follow-up time was 11.8 years. Fewer patients initiated a first bDMARD in the former MTX+pred compared with the former MTX+plac strategy group: 31% vs 50%, p=0.003. At the 2 year post-trial follow-up, the median erosion score was significantly lower in the former MTX+pred versus former MTX+plac strategy group: 0 (range 0-0) versus 0 (0-2), p=0.002. No significant differences between the former strategy groups in the onset of GC-related comorbidities during the post-trial follow-up were found.
Addition of 10 mg prednisone daily to an MTX-based treatment strategy in early rheumatoid arthritis results in a lower initiation rate of a first bDMARD and significantly better radiographic outcomes, yet does not result in more GC-related comorbidities.
The CAMERA-II trial compared two tight-control, treat-to-target strategies, initiating methotrexate with prednisone (MTX+pred) or MTX with placebo (MTX+plac), in early RA-patients. The ...multi-biomarker disease activity (MBDA) blood test objectively measures RA disease activity with a score of 1-100. In CAMERA-II, response profiles of the MBDA score, its individual biomarkers, and DAS28 were assessed.
We evaluated 92 patients from CAMERA-II of whom clinical data and serum for MBDA testing at baseline and ≥ 1 time-point from months 1, 2, 3, 4, 5, 6, 9, or 12 were available. Changes (∆) from baseline for DAS28 and MBDA score and comparisons of ∆DAS28 and ∆MBDA score over time within the MTX+pred versus the MTX+plac strategy were tested for significance with t tests. Changes in biomarker concentration from baseline to months 1-5 were tested with Wilcoxon signed rank test and tested for difference between treatment arms by Mann-Whitney U test.
MBDA and DAS28 showed similar response profiles, with gradual improvement over the first 6 months in the MTX+plac group, and in the MTX+pred group faster improvement during month 1, followed by gradual improvement. The 12 MBDA biomarkers could be grouped into 4 categories of response profiles, with significant responses for 4 biomarkers during the MTX+plac strategy and 9 biomarkers during the MTX+pred strategy.
MBDA tracked treatment response in CAMERA-II similarly to DAS28. More individual MBDA biomarkers tracked treatment response to MTX+pred than to MTX+plac. Four response profiles could be observed.
CAMERA-II International Standard Randomised Controlled Trial Number: ISRCTN 70365169 . Registered on 29 March 2006, retrospectively registered.
Background
Presently, no validated data exist on symptom severity and disease‐specific quality‐of‐life (QoL) for patients with mastocytosis. Simultaneously, clinical trials and drug application ...processes increasingly mandate reporting patients’ perspectives on symptoms and QoL. We report on the development and validation of the mastocytosis quality‐of‐life questionnaire (MQLQ) and the mastocytosis symptom assessment form (MSAF).
Methods
Both outcome measures were developed in a standardized stepwise method, starting with the identification of items in focus groups (n = 12), item reduction and subsequent cross‐sectional validation in a 63% female cohort of 164 adult patients with indolent systemic mastocytosis.
Results
The MSAF reveals that fatigue is the severest mastocytosis symptom while the MQLQ indicates that fear of anaphylaxis mostly impacts QoL. Cross‐sectional validity was assessed by correlating both individual domains and the total scores of the MQLQ and MSAF with independent measures of mastocytosis. The total scores of both the MQLQ (P < 0.001; Spearman's r: 0.568) and the MSAF (P < 0.001; Spearman's r: 0.559) correlated significantly with the consensus on physician‐scored mediator symptoms. The MQLQ domains displayed a high internal consistency (Cronbach's alpha: 0.841–0.958) and the domains ‘bones’, ‘skin symptoms’ and ‘anaphylaxis’ differed significantly between patients with and without osteoporosis, urticaria pigmentosa or anaphylaxis, respectively (P < 0.001).
Conclusions
The MQLQ is the first disease‐specific QoL questionnaire for mastocytosis and is complemented by the MSAF, a short and convenient symptom scoring form. Both patient‐reported outcome measures are valid, reliable and discriminate between patients with different disease characteristics, making them useful instruments for clinical research.
Abstract
The dates are stacked in a basin with four sloping walls, and the sugary juice flows out of the dates under the influence of pressure, heat, and humidity; this is the common method of ...molasses in Iraq, and it was developed as part of this study. Teardrop molasses is a specific variety that is packaged in teardrop-shaped containers. Although this technique (the tampers) is effective in removing sugar and nutrients from dates without spoiling them, and in obtaining sugary juice with a light natural color, it comes with a low production rate because the syrup does not exceed 10-15% of the weight of the dates, and because it takes a long period of time to produce (from 2 to 3 months). As a result, the study aimed to increase production and the best physical, chemical, and sensory quality attributes in the product by employing a new synergistic strategy to raise the extraction efficiency and improve the quality of molasses during the manufacturing process. The study found that the created method was superior (synergy) because it increased the efficiency of making date molasses to 38% of the utilized dates and cut the production time in half, from two months to three days. The sensory evaluation found that this approach also fared exceptionally well across the board of sight, sound, and touch. As one of the local soft date varieties, Sukkari performed better than the other varieties of Zahdi (of semi-dry dates) and Khastawi (of the soft date varieties) utilized in the study, demonstrating the effect of the date variety on the amount of production.
Abstract
The objective of this study was to assess the impact of date cultivar and processing technique on the chemical composition, qualitative attributes, and quantitative characteristics of date ...molasses. Two Iraqi date varieties, namely Al-Zuhdi and Al-Khastawi, were chosen during the date stage to produce date molasses using three established methods: the Madabis method, the foundry method (hot water) and the modern mechanical method (synergistic). The results of the comparison of the physical characteristics of the fruits of date palm (Phoenix dactylifera L.) between the two cultivars Zahdi and Khastawi showed that the fruits of the Khastawi variety were superior to the Zahdi variety in weight, length, diameter, size, and weight of the fleshy part. Significant differences were also recorded in the chemical properties of the dates used in the study, as the Zuhdi variety recorded the highest percentage of ash, protein, fat and total acidity, while the Khastawi variety recorded the highest percentage of total sugars. The results showed that there were significant differences between the studied molasses samples in terms of production, as the sample (Khastawi W3) of molasses produced by the synergistic method recorded the highest production rate of date molasses (643.7) g / kg of dates, with a slight difference from the closest value recorded by the same manufacturing method for the Zahdi variety (591.3). g/kg). As for the biological test for the microbial molasses content of bacteria and molds, the molasses manufactured by three methods and for the two varieties under study met the limits of microbiological safety, under normal storage conditions at room temperature even after 90 days without recording any microbiological infection. All samples of molasses were accepted with a very good degree in the sensory evaluation of the qualities of texture, smell, taste and color, while the Zahdi variety by the traditional cold pressing method (Madabis) scored the best final acceptance score.
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