Predictors of a placebo response in patients with hand osteoarthritis: post-hoc analysis of two randomized controlled trials

Background Placebo can have a significant therapeutic effect in patients with hand osteoarthritis (OA). This aim of the study is to identify factors associated with a clinically meaningful placebo response in patients with hand OA. Methods This post-hoc analysis of two double-blind, placebo-controlled, randomized trials (RCTs) investigating the efficacy of GCSB-5 or diacerein as treatments for hand OA analyzed the efficacy of a placebo. Clinical and laboratory factors associated with a clinically meaningful response, defined as an improvement in the Australian/Canadian Osteoarthritis Hand Index (AUSCAN) pain score > 10 at 4 weeks relative to baseline, were identified. Results The mean improvement in the AUSCAN pain score was − 6.0 ± 20.3, with marked variation between 143 hand OA patients (range: − 76.4 to 33.2). A clinically meaningful improvement was observed in 54 (37.8%) patients. Placebo responders had worse AUSCAN pain scores (55.7 ± 19.7 vs. 43.6 ± 21.6, p = 0.001) and a worse AUSCAN stiffness (68.2 ± 20.5 vs. 57.5 ± 24.5, p = 0.008) at baseline than non-responders. Improvements in pain correlated with the baseline pain level (Pearson r = − 427, p < 0.001). Structural joint changes such as tender, swollen, enlarged, or deformed joint counts did not differ between placebo responders and non-responders. In a multivariable analysis, only baseline AUSCAN pain was associated with a clinically meaningful placebo response (OR: 1.054, 95% CI [1.019–1.089], p = 0.002). Conclusions High levels of pain at baseline are predictive of a clinically meaningful placebo response in patients with hand OA. Further studies are needed to optimize and utilize the benefit of placebo responses in patients with hand OA.This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI15C1136, HC17C0069)

Survival rates of cancer patients with and without rheumatic disease: a retrospective cohort analysis

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Background To compare the outcomes of gastric, colon, lung, and breast cancer patients with and without rheumatic diseases (RD). Methods This retrospective study compared the cancer survival rates of a cohort of 122 cancer patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), dermatomyositis/polymyositis (DM/PM), or systemic sclerosis with that of a cohort of 366 age-, sex-, and, cancer type-matched patients without RD who received medical care from 2000 to 2014. Staging, comorbidities, and functional status were ascertained. Survival was compared using the Kaplan-Meier method. Relative risk of death was estimated as a hazard ratio (HR) using Cox regression analysis. Results The mean age of the RD patients at the time of cancer diagnosis was 58.7 ± 11.5 years. The overall survival rate of gastric cancer patients did not differ between the cohorts. The survival of lung or breast cancer was worse in patients with RA or DM/PM than in those without RD (all, p < 0.05). After adjusting for cancer stage, comorbidity index, performance status and age at the time of cancer diagnosis (as well as interstitial lung disease for lung cancer group), the mortality rate among lung cancer patients with RA was significantly higher (HR, 1.81; 95 % CI, 1.03–3.18) than that of lung cancer patients without RD, whereas SSc was associated with decreased mortality of lung cancer (HR, 0.16; 95 % CI, 0.04–0.58). DM/PM were associated with increased mortality of breast cancer patients (HR, 297.39; 95 % CI, 4.24–20842.33). Conclusions RA and DM/PM seemed to be associated with a higher mortality in patients with lung or breast cancers, whereas SSc seemed to be associated with decreased mortality in patients with lung cancer. It is warranted to explore the survival effect of tailored cancer treatments according to specific RD

Altered lipoproteins in patients with systemic lupus erythematosus are associated with augmented oxidative stress: a potential role in atherosclerosis

Background To examine the structural and oxidative properties of lipoproteins from patients with systemic lupus erythematosus (SLE). Methods The lipid profiles of 35 SLE patients and 15 healthy controls (HCs) were compared. Oxidation status, susceptibility to oxidation, and structural integrity of low-density lipoprotein (LDL) were determined by measuring malondialdehyde (MDA), de novo formation of conjugated dienes in the presence of CuSO4, and mobility on gel electrophoresis, respectively. In vitro foam cell formation and the oxidative potential in zebrafish embryos were examined. Results LDL levels in SLE patients and HCs were similar (p = 0.277). LDL from SLE patients was more fragmented than that from HCs. In addition, LDL from SLE patients was more oxidized than LDL from HCs (p < 0.001) and more susceptible to de novo oxidation (p < 0.001) in vitro. THP-1 cells engulfed more LDL from SLE patients than LDL from HCs (p < 0.001). LDL from SLE patients, which was injected into zebrafish embryos, induced a higher degree of oxidation and a higher mortality than LDL from HCs (both p < 0.001). The survival of embryos treated with oxidized LDL was significantly better in the presence of HDL3 from HCs than that from SLE patients (all p < 0.001). Conclusions Lipoproteins from SLE patients exhibited greater oxidative potential, which might contribute to accelerated atherosclerosis in SLE

An Increase in Peripheral Temperature following Cocaine Administration Is Mediated through Activation of Dopamine D2 Receptor in Rats

Drug addiction has become a worldwide problem, affecting millions of people across the globe. While the majority of mechanistic studies on drug addiction have been focused on the central nervous system, including the mesolimbic dopamine system, the peripheral actions of drugs of abuse remain largely unknown. Our preliminary study found that the systemic injection of cocaine increased peripheral skin temperature. This led us to our present study, which investigated the mechanisms underlying the increase in peripheral temperature following cocaine injection. Male Sprague Dawley rats were anesthetized with pentobarbital sodium, and peripheral skin temperature measurements were taken using a thermocouple needle microprobe and an infrared thermal camera. Cocaine injection caused an acute rise in peripheral body temperature, but not core body temperature, about 10 min after injection, and the temperature increases were occluded by systemic injection of dopamine D2 receptor antagonist L741,626, but not D1 receptor antagonist SCH23390. In addition, systemic administration of bromocriptine, a dopamine D2 receptor agonist, significantly increased peripheral temperature. Infrared thermal imaging showed that the thermal increases following cocaine injection were predominantly in the distal areas of the forelimbs and hindlimbs, relative to core body temperature. Treatment with cocaine or bromocriptine decreased the size of skin blood vessels without affecting the expression of dopamine D2 receptors. These results suggest that increased peripheral temperature in skin following cocaine injection is associated with the activation of the dopamine D2 receptor