This trial evaluated the efficacy and safety of GZ389988A, a tropomyosin receptor kinase A (TrkA) inhibitor, in subjects with painful knee osteoarthritis (OA).
In this single center, double-blind, ...placebo-controlled and randomized trial, 104 subjects with moderate-to-severe knee OA pain were enrolled to receive a single intra-articular (IA) injection of either GZ389988A or placebo. Efficacy measures were assessed over 12 weeks and included walking pain (Western Ontario and McMaster Universities Osteoarthritis Index WOMAC A1), overall knee pain, WOMAC A, B, C and total score, Patient Global Impression of Change (PGIC), OMERACT-OARSI responder rate and rescue medication use. Adverse events (AEs) were monitored up to 24 weeks.
The primary efficacy endpoint was met with a between-group difference of −7.49 (VAS 0–100) on WOMAC A1 changes over 4 weeks (P < 0.05 favoring GZ389988A). The secondary outcome on WOMAC A1 changes over 12 weeks had a between-group difference of −6.78 (P = 0.064). Among weekly assessments, statistically significant greater improvement in the GZ389988A group was observed in WOMAC A1, overall knee pain and/or WOMAC A at weeks 2–5. Although not statistically significant, improvements over placebo on pain and WOMAC C persisted over 12 weeks. Greater AE incidence was observed in the GZ389988A group including transient and self-limited injection joint inflammatory reactions with a spike of acetaminophen intake within the first week post-injection.
IA injection of TrkA inhibitor GZ389988A in knee OA subjects reduced pain with a numerically functional gain and an acceptable safety profile. (ClinicalTrials.gov, NCT02845271).
Obesity is considered as a chronic disease that can induce a series of comorbidities and complications. Chinese medicine has long clinical experiences in the treatment of obesity. This review ...summarizes the natural products from traditional Chinese medicine (TCM) that are reported to have anti‐obesity effects in the past two decades. Botanic TCM comprises 90% of total Chinese crude drugs, and generally contains various active ingredients, in which the effective anti‐obesity ingredients identified can be divided into saponins, polysaccharides, alkaloids, polyphenols and others. Astragaloside IV, glycyrrhizin, macrostemonoside A, berberine, betaine, capsaicin, matrine, methyl piperate, piperine, rutaecarpine, asimilobine, epigallocatechingallate, magnolol, resveratrol, soybean‐isoflavone, α‐linolenic acid, emodin, geniposide, phillyrin, salidroside and ursolic acid are specified in this review, and their sources, models, efficacy are described. It is concluded that the mechanisms of these components for the treatment of obesity include: (i) suppression of appetite, increase of satiety, reduction of energy intake; (ii) reduction in the digestion and absorption of exogenous lipid; (iii) attenuation of the synthesis of endogenous lipid; (iv) promotion of the oxidation and expenditure of lipid and (v) improvement of lipid metabolism disorder. Authors believe that the effective compounds from TCM will provide an alternative and hopeful way for the treatment of obesity.
Summary The goal of this document is to update the original OARSI recommendations specifically for the design, conduct, and reporting of clinical trials that target symptom or structure modification ...among individuals with knee osteoarthritis (OA). To develop recommendations for the design, conduct, and reporting of clinical trials for knee OA we initially drafted recommendations through an iterative process. Members of the working group included representatives from industry and academia. After the working group members reviewed a final draft, they scored the appropriateness for recommendations. After the members voted we calculated the median score among the nine members of the working group who completed the score. The document includes 25 recommendations regarding randomization, blocking and stratification, blinding, enhancing accuracy of patient-reported outcomes (PRO), selecting a study population and index knee, describing interventions, patient-reported and physical performance measures, structural outcome measures, biochemical biomarkers, and reporting recommendations. In summary, the working group identified 25 recommendations that represent the current best practices regarding clinical trials that target symptom or structure modification among individuals with knee OA. These updated recommendations incorporate novel technologies (e.g., magnetic resonance imaging (MRI)) and strategies to address the heterogeneity of knee OA.
This paper reports probably the first systematic experimental investigation of the influences of lateral inertia confinement, end friction confinement and aggregates in high-speed impact tests on ...dynamic compressive properties of concrete. The influences of the concerned factors on the dynamic increase factor (DIF) are discussed. The proposed DIF relations in Hao and Hao 36 are verified by the experimental data in this study. The results confirm the observations made before based on numerical simulations that lateral inertia confinement effect is dependent on the specimen diameter and strain rate. The influences of aggregate size and volume to DIF are considerable, and aggregates cannot be neglected in experimental or numerical studies. It also confirms that the end friction confinement effect is sensitive to the specimen geometry and strain rate. The equation proposed in Hao et al. 40 based on numerical simulations satisfactorily removes the friction confinement effect on the DIF of concrete material strength obtained in impact test.
Summary Hand osteoarthritis (OA) is a very frequent disease, but yet understudied. However, a lot of works have been published in the past 10 years, and much has been done to better understand its ...clinical course and structural progression. Despite this new knowledge, few therapeutic trials have been conducted in hand OA. The last OARSI recommendations for the conduct of clinical trials in hand OA dates back to 2006. The present recommendations aimed at updating previous recommendations, by incorporating new data. The purpose of this expert opinion, consensus driven exercise is to provide evidence-based guidance on the design, execution and analysis of clinical trials in hand OA, where published evidence is available, supplemented by expert opinion, where evidence is lacking, to perform clinical trials in hand OA, both for symptom and for structure-modification. They indicate core outcome measurement sets for studies in hand OA, and list the methods and instruments that should be used to measure symptoms or structure. For both symptom- and structure-modification, at least pain, physical function, patient global assessment, HR-QoL, joint activity and hand strength should be assessed. In addition, for structure-modification trials, structural progression should be measured by radiographic changes. We also provide a research agenda listing many unsolved issues that seem to most urgently need to be addressed from the perspective of performing “good” clinical trials in hand OA. These updated OARSI recommendations should allow for better standardizing the conduct of clinical trials in hand OA in the next future.
Hip osteoarthritis (OA) is difficult to treat. Steroid injections reduce pain with short duration. With widespread adoption of office-based, image-guided injections, hyaluronic acid is a potentially ...relevant therapy. In the largest clinical trial to-date, we compared safety/efficacy of a single, 6-mL image-guided injection of hylan G-F 20 to saline in painful hip OA.
357 patients were enrolled in a multicenter, double-blind, randomized saline placebo- controlled trial. Subjects were ≥35 years of age, with painful (Western Ontario and McMaster Universities Osteoarthritis Index WOMAC-A1:5.0–8.0; numeric rating scale NRS: 0–10) mild-to-moderate hip OA (Kellgren–Lawrence grade II/III) and minimal contralateral hip pain (WOMAC-A1 < 4). Outcome measures included “pain on walking” (WOMAC-A1 and -A), Patient Global Self-Assessment (PTGA), WOMAC-A1 responder rate (+≥2 points on NRS), and adverse events (AEs) over 26 weeks.
357 patients (hylan G-F 20 single:182; saline:175) were enrolled. Both groups demonstrated significant pain improvement from baseline over 26 weeks (P < 0.0001); saline-induced pain reduction was a remarkable 35%. WOMAC-A and PTGA scores also significantly improved (P < 0.0001). No statistically significant difference was observed between groups in WOMAC-A1 scores (hylan G-F 20 single:−2.19 ± 0.16; saline:−2.26 ± 0.17) or WOMAC-A1 responders (41–52%). Treatment-related AE rates at target hip were similar (hylan G-F 20 single:23 patients 12.8%; saline:12 7.0%). Posthoc analysis found, despite protocol requirements, many patients had psychological (31%) or potential neuropathic pain (27.5%) conditions.
A single 6-mL hylan G-F 20 injection or saline for painful hip OA resulted in similar, statistically significant/clinically relevant pain and function improvements up to 6 months following injection; no differences between hylan G-F 20 and saline placebo were observed.
This randomized, phase 3 trial compared the effectiveness of roxadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, with epoetin alfa in patients undergoing hemodialysis or ...peritoneal dialysis in China. Oral roxadustat was noninferior to parenteral epoetin alfa as therapy for anemia.
As the most apical structure between epithelial and endothelial cells, tight junctions (TJ) are well known as functioning as a control for the paracellular diffusion of ions and certain molecules. It ...has however, become increasingly apparent that the TJ has a vital role in maintaining cell to cell integrity and that the loss of cohesion of the structure can lead to invasion and thus metastasis of cancer cells. This article will present data showing how modulation of expression of TJ molecules results in key changes in TJ barrier function leading to the successful metastasis of a number of different cancer types.
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