People in Spite of History Várady, Tibor; Buxbaum, Richard; Boris, János
2021, 20210120, 2021-01-20
eBook
Three generations of a family of lawyers have run a firm founded in 1893 in the small city of Becskerek (today in Serbian Zrenjanin), first part of the Austro-Hungarian Habsburg monarchy, then ...Hungary, then Yugoslavia, then for a while under German occupation, then again part of Yugoslavia and finally Serbia. In the Banat district of the province of Vojvodina, the multiplicity of languages and religions and changes of place-names was a matter of course. What is practically unprecedented, all files, folders and documents of the law office have survived. They concern marriages, divorces, births and testaments, as well as expulsions, emigrations, incarcerations and releases of these largely rural and small-town dwellers. Mundane cases reflect times through war, peace, revolution and counter-revolution, through serfdom and freedom, through comfort and poverty. The files also show everyday lives shaped in spite of history. Tibor Várady transforms them into affecting and vivid vignettes, selecting and commenting without sentimentality but with empathy. The law office of the three generations of the Várady family demonstrates that the legal profession permits and in difficult times even requires its members to defend the ordinary men and women against the powers of state and society.
Objective
The objective of this study was to describe the real‐world characteristics and clinical status of patients with psoriatic arthritis (PsA) currently prescribed ixekizumab.
Methods
Data were ...drawn from the Adelphi PsA Plus Disease Specific Programme (DSP), a cross‐sectional survey conducted in the United States between September 2021 and March 2022. Rheumatologists provided data for their next five consulting patients currently receiving ixekizumab, including demographic and clinical characteristics, disease severity, treatment history, reasons for treatment choice, satisfaction with current treatment, and current and historic symptom burden. Patients voluntarily completed questionnaires, providing perceptional data on symptom burden and satisfaction with current treatment.
Results
Overall, 68 rheumatologists provided data on 275 patients with PsA, 90 of whom completed the voluntary questionnaire. Patients had been prescribed ixekizumab for a mean of 11.7 (SD 10.6) months. Clinical characteristics, disease severity, and symptom burden of patients with PsA improved significantly from ixekizumab initiation to the most recent consultation, including symptom burden, tender and swollen joint counts, and body surface area affected by psoriasis (all P < 0.001). Both rheumatologists and patients were satisfied with ixekizumab treatment and reported improvements in pain and fatigue. Improvements were noted after more than three months of ixekizumab treatment duration and regardless of whether the patients had prior exposure to an advanced therapy or were treatment naïve.
Conclusion
Our results indicate that ixekizumab was efficacious in the treatment of PsA in real‐world clinical practice, complementing efficacy data from randomized controlled clinical trials. The results of this study may assist rheumatologists and their patients in making informed treatment choices.
Context:
Recent studies on the mechanism of action (MOA) of bone-active drugs have rekindled interest in how to present and interpret dynamic histomorphometric parameters of bone remodeling.
...Objective:
We compared the effects of an established anabolic agent, teriparatide (TPTD), with those of a prototypical antiresorptive agent, zoledronic acid (ZOL).
Design:
This was a 12-month, randomized, double-blind, active-comparator controlled, cross-sectional biopsy study.
Setting:
The study was conducted at 12 U.S. and Canadian centers.
Subjects:
Healthy postmenopausal women with osteoporosis participated in the study.
Interventions:
Subjects received TPTD 20 μg once daily by sc injection (n = 34) or ZOL 5 mg by iv infusion at baseline (n = 35).
Main Outcome Measures:
The primary end point was mineralizing surface/bone surface (MS/BS), a dynamic measure of bone formation, at month 6. A standard panel of dynamic and static histomorphometric indices was also assessed. When specimens with missing labels were encountered, several methods were used to calculate mineral apposition rate (MAR). Serum markers of bone turnover were also measured.
Results:
Among 58 subjects with evaluable biopsies (TPTD = 28; ZOL = 30), MS/BS was significantly higher in the TPTD group (median: 5.60 vs. 0.16%, P < 0.001). Other bone formation indices, including MAR, were also higher in the TPTD group (P < 0.05). TPTD significantly increased procollagen type 1 N-terminal propeptide (PINP) at months 1, 3, 6, and 12 and carboxyterminal cross-linking telopeptide of collagen type 1 (CTX) from months 3 to 12. ZOL significantly decreased PINP and CTX below baseline at all time points.
Conclusions:
TPTD and ZOL possess fundamentally different mechanisms of action with opposite effects on bone formation based on this analysis of both histomorphometric data and serum markers of bone formation and resorption. An important mechanistic difference was a substantially higher MS/BS in the TPTD group. Overall, these results define the dynamic histomorphometric characteristics of anabolic activity relative to antiresorptive activity after treatment with these two drugs.
BackgroundThe Assessment of SpondyloArthritis international Society-European Alliance of Associations for Rheumatology recommendations for axial spondyloarthritis (axSpA) management include patient ...assessment for biological disease-modifying antirheumatic drug (bDMARD) treatment response after at least 12 weeks of treatment. The current treat-to-target strategy for axSpA is to achieve inactive disease (ID; Axial Spondyloarthritis Disease Activity Score (ASDAS) <1.3) or at least low disease activity (LDA; 1.3≤ASDAS<2.1).To investigate the association between treatment response at week 12 and/or week 24 and attainment of the ASDAS<2.1 treat-to-target recommendation at week 52 in bDMARD-naïve patients with radiographic (r-)axSpA treated with ixekizumab (IXE).MethodsThis post hoc analysis included patients randomly assigned to IXE 80 mg every 4 weeks from COAST-V (NCT02696785), a phase 3 trial in bDMARD-naïve patients with r-axSpA. The proportion of patients who achieved ASDAS<2.1 at week 52 was measured among those who attained or not clinically important improvement (CII, ∆ASDAS≥1.1) response, and among those with ID, LDA and high or very high disease activity at week 12 and/or week 24. Non-response was assumed for missing data.ResultsAmongst 81 patients, 47 (58.0%) achieved ASDAS CII at week 12, with 70.2% (n=33) achieving ASDAS<2.1 at week 52. At week 24, 52 (64.2%) patients achieved ASDAS CII, with 71.2% (n=37) achieving ASDAS<2.1 at week 52. Of the 24 patients who did not achieve ASDAS CII at either week 12 or week 24, 5 (20.8%) achieved ASDAS<2.1 at week 52.ConclusionThis analysis reinforces the current recommendation that continuing treatment in those achieving ASDAS CII at week 12 and/or week 24 increases the likelihood of obtaining ID/LDA at week 52.Trial registration numberNCT02696785.
To gain insight into how teriparatide affects various bone health parameters, we assessed the effects of teriparatide treatment with use of standard DXA (dual x-ray absorptiometry) technology and two ...newer technologies, high-resolution MRI (magnetic resonance imaging) and finite element analysis of quantitative CT (computed tomography) scans.
In this phase-4, open-label study, postmenopausal women with severe osteoporosis received 20 μg/day of teriparatide. Assessments included (1) changes in areal BMD (bone mineral density) (in g/cm
) at the radius, spine, and hip on DXA, (2) changes in volumetric BMD (in mg/cm
) at the spine and hip on quantitative CT scans, (3) changes in bone microarchitecture at the radius on high-resolution MRI, (4) estimated changes in spine and hip strength according to finite element analysis of quantitative CT scans, (5) changes in bone turnover markers in serum, and (6) safety.
Thirty-five subjects were enrolled; thirty completed eighteen months and twenty-five completed an optional six-month extension. No significant changes were observed for the primary outcome, high-resolution MRI at the distal aspect of the radius. At month eighteen, the least-squares mean percentage change from baseline in total volumetric BMD at the spine was 10.05% (95% confidence interval CI, 6.83% to 13.26%; p < 0.001), and estimated spine strength increased 17.43% (95% CI, 12.09% to 22.76%; p < 0.001). Total volumetric BMD at the hip increased 2.22% (95% CI, 0.37% to 4.06%; p = 0.021), and estimated hip strength increased 2.54% (95% CI, 0.06% to 5.01%; p = 0.045). Areal BMD increased at the lumbar spine and femoral neck, was unchanged for the total hip and at the distalmost aspect of the radius, and decreased at a point one-third of the distance between the wrist and elbow. Bone turnover markers increased at months three, six, and twenty-four (all p < 0.05). No unexpected adverse events were observed.
High-resolution MRI failed to identify changes in bone microarchitecture at the distal aspect of the radius, a non-weight-bearing site that may not be suitable for assessing effects of an osteoanabolic agent. Teriparatide increased areal BMD at the spine and femoral neck and volumetric BMD at the spine and hip. Estimated vertebral and femoral strength also increased. These findings and increases in bone turnover markers through month twenty-four are consistent with the known osteoanabolic effect of teriparatide.
Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
In a Maelstrom Hetenyi, Zsuzsa
2008, 20080120, 2008-01-10
eBook
The first concise history of Russian-Jewish literary prose, this book discusses Russian-Jewish literarature in four periods, analyzing the turning points (1881–82, 1897, 1917) and proposing that the ...selected epoch (1860–1940) represents a special strand that was unfairly left out of both Russian and Jewish national literatures. Based on theoretical sources on the subject, the book establishes the criteria of dual cultural affiliation, and in a survey of Russian-Jewish literature presents the pitfalls of assimilation and discusses different forms of anti-Semitism. After showing the oeuvre of 18 representative authors as a whole, the book analyzes a number of characteristic novels and short stories in terms of contemporary literary studies. Many texts discussed have not been reprinted since their first publication. The material offers indispensable information not only for comparative and literary studies but for multicultural, historical, ethnographic, Judaist, religious and linguistic investigations as well.
Fledgling dictatorships and authoritarian regimes typically pamper their armed forces and law enforcement agencies, showering money and privileges on their members in order to win their loyalty and ...have them safely on their side in case of possible confrontations with the masses. If that were a measuring stick showing whether a system of government is dictatorial or not, then the Orbán regime in Hungary would certainly not qualify. There was, in fact, a piece of new legislation running against the interests of soldiers, policemen, and firefighters in 2010, retroactively canceling their traditional early retirement benefits, which provided the original “single
Context:
Denosumab-induced PTH elevation may stimulate early bone formation.
Objective:
Our objective was to evaluate whether denosumab-induced changes of intact PTH (iPTH) result in early anabolic ...effects according to histomorphometry and bone turnover markers (BTMs) compared with teriparatide, an established anabolic agent.
Design:
This open-label, randomized study used quadruple labeling to label bone before/after treatment, with a transiliac bone biopsy at 3 months.
Setting:
This study took both in both US and Canadian sites.
Participants:
Sixty-nine postmenopausal women with osteoporosis were included.
Interventions:
Teriparatide (20 μg/day) for 6 months and denosumab (60 mg once) were used in this study.
Main Outcome Measure:
Between-treatment comparison of change from baseline to month 3 in cancellous mineralizing surface/bone surface, histomorphometric indices in four bone envelopes, and BTM and iPTH at baseline, 1, 3, and 6 months was undertaken.
Results:
After denosumab, iPTH peaked at month 1 (P < .001), then declined, remaining above baseline through month 6 (P ≤ .01); after teriparatide, iPTH declined at all time points (P < .001). From baseline to month 3, cancellous mineralizing surface/bone surface increased with teriparatide and decreased with denosumab and at month 3, was higher with teriparatide. Similar results were observed in other bone envelopes. BTMs increased from baseline in teriparatide-treated subjects (procollagen type 1 N-terminal propeptide at month 1 and carboxyterminal cross-linking telopeptide of type 1 collagen at month 3); procollagen type 1 N-terminal propeptide and carboxyterminal cross-linking telopeptide of type 1 collagen decreased from baseline at all time points in denosumab-treated subjects.
Conclusions:
Denosumab treatment increased iPTH but inhibited bone formation indices. In contrast, teriparatide treatment decreased iPTH but stimulated bone formation indices. These findings are not consistent with the hypothesis of early indirect anabolic effect with denosumab.
We compared effects of teriparatide and denosumab on PTH, bone turnover markers, and bone histomorphometry in osteoporotic postmenopausal women. The findings were inconsistent with an early indirect anabolic effect of denosumab.
PDF
